This study presents the first development and validation of a static multiple light scattering(SMLS)-based method for real-time,non-invasive assessment of nanoparticle colloidal stability.Nanoparticles,leveraging thei...This study presents the first development and validation of a static multiple light scattering(SMLS)-based method for real-time,non-invasive assessment of nanoparticle colloidal stability.Nanoparticles,leveraging their nanoscale advantages(e.g.,targeted delivery,enhanced drug solubility,and controlled release),hold transformative potential in treating diseases.However,their clinical success hinges on colloidal stability,which dictates in vivo behavior,safety,and regulatory compliance.While dynamic light scattering(DLS)remains widely used,its inability to monitor dynamic transformations and reliance on sample dilution limit its accuracy.Here,we pioneer the application of SMLS to systematically evaluate colloidal stability across standardized particles and commercial nanoparticle formulations(liposomes,nanoparticles,micelles,and nanoemulsions).Results demonstrate that SMLS captures destabilization kinetics(aggregation,sedimentation,and creaming)in real-time without dilution,even at high concentrations,while DLS fails to distinguish polydisperse systems due to time-point sampling.The Turbiscan stability index(TSI)quantifies instability mechanisms,correlating with particle size distribution broadening.This first comprehensive validation of SMLS for nanoparticles reveals its superiority in reflecting native-state behavior,exemplified by minimal or the variations in the average transmission(ΔT)or backscattering intensity(ΔBS)fluctuations and low TSI values in four commercial formulations.By addressing a critical technological gap,this study establishes SMLS as an indispensable tool for optimizing nanoparticle design,ensuring compliance with U.S.Food and Drug Administration(FDA)in-use stability guidelines,and accelerating clinical translation.展开更多
Compared to synthetic chemical compounds,plant extracts derived from natural sources have emerged as the"new favorites"in the treatment and care of skin diseases due to their distinct advantages,including be...Compared to synthetic chemical compounds,plant extracts derived from natural sources have emerged as the"new favorites"in the treatment and care of skin diseases due to their distinct advantages,including being environmentally friendly,sustainable,and safe.However,challenges such as poor solubility,limited permeability,and the barrier function of the stratum corneum significantly restrict the application of natural products in dermal drug delivery.Fortunately,advancements in nanotechnology offer promising solutions to overcome these challenges.Different skin diseases and treatments require the precise delivery of natural active ingredients to specific skin layers,and the unique structure of nanocarriers enables targeted delivery to achieve desired therapeutic outcomes.This paper begins by exploring the pathogenesis and therapeutic targets of common skin conditions,including atopic dermatitis(AD),psoriasis,decubitus ulcers,diabetic foot ulcers(DFUs),as well as applications in antioxidant therapies and anti-aging strategies.Furthermore,it provides a detailed overview of the depths and locations within the skin where active compounds must be delivered to exert their effects effectively.Subsequently,this review categorizes and examines natural products based on their therapeutic effects on various skin diseases.It then highlights the skin depths and specific sites that can be targeted by different delivery systems designed to enhance skin permeability,tailored to meet the needs of skin disease treatment or care.By addressing these aspects,this review aims to provide a valuable reference for advancing research on nano-delivery systems in the field of topical skin drug delivery for the treatment and management of skin diseases.展开更多
Skin aging is a multifactorial biological process driven by oxidative stress(OS),chronic inflammation,cellular senescence,mitochondrial dysfunction,and non-enzymatic glycation(NEG),and is markedly accelerated by envir...Skin aging is a multifactorial biological process driven by oxidative stress(OS),chronic inflammation,cellular senescence,mitochondrial dysfunction,and non-enzymatic glycation(NEG),and is markedly accelerated by environmental stressors such as ultraviolet radiation(UVR)and air pollution.Natural bioactive compounds,including flavonoids,polyphenols,terpenoids,alkaloids,vitamins,polysaccharides,peptides,and indole derivatives,have demonstrated considerable potential in mitigating these processes through multi-target antioxidant,anti-inflammatory,anti-photoaging,and extracellular matrix(ECM)-protective mechanisms.However,their clinical and cosmetic translation is often limited by poor solubility,chemical instability,and insufficient skin penetration.Rather than providing a simple compilation of existing studies,this review offers a mechanism-oriented and delivery-driven synthesis of recent advances in natural anti-skin-aging research.We systematically integrate current knowledge on the molecular drivers of skin aging with a critical comparison of emerging transdermal and nanotechnology-based delivery systems,including lipid-based,polymer-based,inorganic/hybrid,and nucleic acid-assembled nanocarriers.Particular attention is given to how rational carrier design modulates stability,permeability,skin-layer targeting,and controlled release behavior.Furthermore,this review critically discusses current limitations,contradictory findings across studies,and key translational challenges,and identifies promising future research directions,such as stimuli-responsive systems,skin-layer-specific targeting,and mechanism-guided material selection.By bridging biological mechanisms with delivery material innovation,this work provides a forward-looking framework for the development of safer,more effective,and scientifically grounded anti-skin-aging therapeutics and cosmeceuticals.展开更多
Cadmium(Cd),a pervasive environmental heavy metal pollutant,has been extensively documented for its toxic effects on human health.However,the underlying pathogenic mechanisms of Cd toxicity,spanning molecular to cellu...Cadmium(Cd),a pervasive environmental heavy metal pollutant,has been extensively documented for its toxic effects on human health.However,the underlying pathogenic mechanisms of Cd toxicity,spanning molecular to cellular levels,remain incompletely elucidated and warrant further investigation.Here,quantitative real-time PCR(qRT-PCR)and enzyme-linked immunosorbent assay(ELISA)analyses demonstrated that cadmium exposure induced a pronounced inflammatory response,characterized by significant elevation of interleukin-6(IL-6)and interleukin-8(IL-8)in 16HBE cells.High-throughput sequencing of cadmium-exposed versus control 16HBE cells identified LncPOPDC3-1 as a novel differentially expressed transcript showing marked upregulation during cadmium-triggered inflammation.We found that LncPOPDC3-1 accelerated the progression of inflammation,including increasing inflammatory factors IL-6 and IL-8.Mechanistically,dual luciferase reporter gene assays and qRT-PCR analysis have demonstrated that LncPOPDC3-1 can directly bind to miR-548a-3p,which regulated the activation of NF-κB signaling pathway.Following inhibition of the NF-κB signaling pathway,the regulatory effect of LncPOPDC3-1 on Cd-induced inflammation was significantly attenuated.Therefore,our data suggest that LncPOPDC3-1 regulates the activation of NF-κB pathway through competitive bound to miR-548a-3p,which subsequently promotes the Cd-induced inflammation in 16HBE cells.This provides a new mechanism and potential molecular targets for Cd-induced toxicity.展开更多
Objective:CLT-003 is a novel phenylphthalimide derivative encapsulated in poly(lactate-glycolic acid)copolymer nanoparticles using nanotechnology techniques.CLT-003 possesses anti-angiogenetic and antitumor activities...Objective:CLT-003 is a novel phenylphthalimide derivative encapsulated in poly(lactate-glycolic acid)copolymer nanoparticles using nanotechnology techniques.CLT-003 possesses anti-angiogenetic and antitumor activities.Nevertheless,the role and molecular mechanism underlying CLT-003 in pancreatic cancer remain to be elucidated.Methods:Cell proliferation and apoptosis were detected using CCK-8,real-time cell analysis(RTCA),EdU,and flow cytometric assays.Cellular mobility and invasive capacity were detected using wound-healing,Transwell,and cell motility assays.Tumor growth and metastasis were determined using the mouse subcutaneous and pancreatic cancer orthotopic liver metastasis models.The antitumor effects of CLT-003 were evaluated using patient-derived organoid(PDO)and patient-derived xenograft(PDX)models.Results:CLT-003 significantly inhibited cellular proliferation,enhanced cellular apoptosis,and attenuated cellular invasion and migration of pancreatic cancer cells.Mechanistically,CLT-003 suppressed the translation of HIF-1a by inhibiting the PI3K/AKT/mTOR signaling pathway.In the mouse tumor models,CLT-003 significantly inhibited the growth and metastasis of pancreatic tumors.Moreover,the PDO and PDX models showed increased sensitivity to CLT-003 in pancreatic cancer with high HIF-1α expression compared to pancreatic cancer with low HIF-1a expression.Conclusions:This study delineated the role and molecular mechanism of CLT-003 action in impeding the progression of pancreatic cancer and indicated its robust potential for the treatment of pancreatic cancer.展开更多
Obesity and related metabolic syndromes have been recognized as important disease risks,in which the role of adipokines cannot be ignored.Adiponectin(ADP)is one of the key adipokines with various beneficial effects,in...Obesity and related metabolic syndromes have been recognized as important disease risks,in which the role of adipokines cannot be ignored.Adiponectin(ADP)is one of the key adipokines with various beneficial effects,including improving glucose and lipid metabolism,enhancing insulin sensitivity,reducing oxidative stress and inflammation,promoting ceramides degradation,and stimulating adipose tissue vascularity.Based on those,it can serve as a positive regulator in many metabolic syndromes,such as type 2 diabetes(T2D),cardiovascular diseases,non-alcoholic fatty liver disease(NAFLD),sarcopenia,neurodegenerative diseases,and certain cancers.Therefore,a promising therapeutic approach for treating various metabolic diseases may involve elevating ADP levels or activating ADP receptors.The modulation of ADP genes,multimerization,and secretion covers the main processes of ADP generation,providing a comprehensive orientation for the development of more appropriate therapeutic strategies.In order to have a deeper understanding of ADP,this paper will provide an all-encompassing review of ADP.展开更多
Angelicae Pubescentis Radix(APR,Duhuo)is a commonly used traditional Chinese medicine and usually used for the treatments of rheumatic diseases.To assess the chemical composition of APR extract,a sensitive and reliabl...Angelicae Pubescentis Radix(APR,Duhuo)is a commonly used traditional Chinese medicine and usually used for the treatments of rheumatic diseases.To assess the chemical composition of APR extract,a sensitive and reliable UPLC-Q-TOF-MS method was used for qualitative analysis.The separation was achieved on an Agilent SB-C18 column(1.8μm,2.1 mm×50 mm)with a gradient elution system consisting of acetonitrile and water containing 0.1%formic acid.An electrospray ionization(ESI)was used for mass spectrometer,and the data were collected in the positive ion mode,which was operated in a full-scan mode at m/z 100-800.A total of 49 compounds including 46 coumarins were identified according to the MS and MS/MS data.Among them,two were new compounds,and isoangenomalin,scoparone,4-methyl-umbelliferyl acetate,suberenol,trans-dehydroosthol,and oroselone were first reported in APR.展开更多
Ulcerative colitis(UC)is a common progressive inflammatory disease whose incidence has increased rapidly in recent years,and can develop into colorectal cancer in severe cases.There are currently no adequate or effect...Ulcerative colitis(UC)is a common progressive inflammatory disease whose incidence has increased rapidly in recent years,and can develop into colorectal cancer in severe cases.There are currently no adequate or effective treatments for UC due to the fact that some patients have found suboptimal results after repeated administration,while others have experienced adverse effects.With the rapid development of nanotechnology,developing innovative colon-targeting platforms is essential to improving efficacy,reducing side effects,and improving patient compliance.In this review,we summarize the pathophysiological characteristics of UC and the most recent status of numerous nanodrug delivery systems based on different targeting mechanisms in treating UC.Oral,intravenous,and rectal drug delivery nanoparticles targeting the colon are discussed,which can provide ideas for the design of colon-targeting nanoparticles for the treatment of colon diseases,especially for the treatment of UC.Last but not least,we provide a glimpse into the future of colon-targeted delivery systems,as well as future advancements in the field.展开更多
Lipid nanoemulsions are promising nanodrug delivery carriers that can improve the efficacy and safety of paclitaxel(PTX).However,no intravenous lipid emulsion of PTX has been approved for clinical treatment,and system...Lipid nanoemulsions are promising nanodrug delivery carriers that can improve the efficacy and safety of paclitaxel(PTX).However,no intravenous lipid emulsion of PTX has been approved for clinical treatment,and systemic safety profiles have not yet been reported.Here we outline the development of a PTXloaded tumor-targeting intravenous lipid emulsion(PTX Emul)and describe its characteristics,colloidal stability,and systemic safety profiles in terms of acute toxicity,long-term toxicity,and toxicokinetics.We also compare PTX Emul with conventional PTX injection.Results showed that PTX Emul exhibited an ideal average particle size(approximately 160 nm)with narrow size distribution and robust colloidal stability under different conditions.Hypersensitivity reaction and hemolysis tests revealed that PTX Emul did not induce hypersensitivity reactions and had no hemolytic potential.In addition,where the alleviated systemic toxicity of PTX Emul may be attributed to the altered toxicokinetic characteristics in beagle dogs,including the decreased AUC and increased plasma clearance and volume of distribution,PTX Emul alleviated acute and long-term toxicity as evidenced by the enhanced the median lethal dose and approximate lethal dose,moderate body weight change,decreased bone marrow suppression and organ toxicity compared with those under PTX injection at the same dose.A fundamental understanding of the systemic safety profiles,high tumor-targeting efficiency,and superior antitumor activity in vivo of PTX Emul can provide powerful evidence of its therapeutic potential as a future treatment for breast cancer.展开更多
Evodiamine,rutaecarpine,and dehydroevodiamine have been demonstrated as the major alkaloids in the fruits of Euodia rutaecarpa,a well-known traditional Chinese medicine with central nervous system activities.To study ...Evodiamine,rutaecarpine,and dehydroevodiamine have been demonstrated as the major alkaloids in the fruits of Euodia rutaecarpa,a well-known traditional Chinese medicine with central nervous system activities.To study their cerebrospinal fluid pharmacokinetics and cerebral nuclei distribution,the alkaloids were mixed at the weight ratio of 1:1:1 and orally administered via gavage to the rats at each dose of 15 mg/kg.A quick and reliable ultra-performance liquid chromatographic-tandem mass spectrometry method was developed and applied for the simultaneous analysis of the alkaloids in rat cerebrospinal fluid and cerebral nuclei collected at different time points.Non-compartmental pharmacokinetic profiles were calculated,and the distribution in cerebral nuclei was compared.All the tested compounds were absorbed into rat cerebrospinal fluid and distributed to the brain nuclei quickly.Their distribution in different nuclei varied,as evodiamine mainly in cerebellum and brainstem,rutaecarpine with its maximum in the brainstem,and dehydroevodiamine mostly in the cerebellum and hippocampus.They were eliminated from the brain rapidly without long-time accumulation.In summary,this study revealed the targeting discrepancy of evodiamine,rutaecarpine,and dehydroevodiamine in the brain,and highlighted the possibility for drug candidates in the encephalopathy treatment of the fruits of E.rutaecarpa.展开更多
Ulcerative colitis(UC)is a chronic inflammatory bowel disease characterized by persistent inflammation of the colon and disrupted intestinal function.Ramulus mori(Sangzhi)alkaloids(SZ-A),derived from twigs of mulberry...Ulcerative colitis(UC)is a chronic inflammatory bowel disease characterized by persistent inflammation of the colon and disrupted intestinal function.Ramulus mori(Sangzhi)alkaloids(SZ-A),derived from twigs of mulberry,were approved by the National Medical Products Administration in 2020 for treating type 2 diabetes mellitus.Accumulated evidence has confirmed that SZ-A also alleviates non-alcoholic fatty liver disease and ameliorates inflammation,indicating its potential to address inflammation in UC.However,the treatment of UC faces challenges due to low drug delivery efficiency and short retention time.To overcome these challenges,an injectable and adherent in-situ thermo-sensitive hydrogel containing SZ-A was developed for rectal drug delivery,utilizing the thermo-sensitive polymers Poloxamer 407and 188.The thermo-sensitive hydrogel system was designed with a moderate gelation temperature of 32±0.5℃,a short gelation time of 64 s,a p H range of 7-10,high moisturizing capability exceeding 90%,and moderate mechanical strength of 4-5 s.In a rat model with UC,the in situ thermo-sensitive hydrogel significantly extended the retention time at the colonic site and enabled sustained release after rectal administration.Symptoms of UC were markedly reduced following rectal administration of SZ-A thermosensitive hydrogel.Furthermore,the release of inflammatory factors,such as interleukin-1β(IL-1β),IL-6,IL-18,tumor necrosis factor-α(TNF-α),and transforming growth factor-β1(TGF-β1),significantly decreased in the SZ-A thermo-sensitive hydrogel group.The integrity of the colonic mucosal barrier was significantly enhanced following the application of SZ-A thermo-sensitive hydrogel.In conclusion,rectal administration of SZ-A in situ thermo-sensitive hydrogel effectively alleviated UC symptoms,inhibited the secretion of inflammatory factors,and promoted the repair of the colonic mucosal barrier.This approach holds promise as a potential treatment for UC.展开更多
Duliang Pill(DLP),consisting of Baizhi and Chuanxiong,is the classical formula of traditional Chinese medicine.In order to investigate the substance basis of DLP,we developed a highly sensitive and reliable UPLC-MS/MS...Duliang Pill(DLP),consisting of Baizhi and Chuanxiong,is the classical formula of traditional Chinese medicine.In order to investigate the substance basis of DLP,we developed a highly sensitive and reliable UPLC-MS/MS method capable of simultaneously detecting 37 constituents from both Baizhi and Chuanxiong.To achieve chromatographic separation,we utilized a Diamonsil C18column along with a mobile phase consisting of acetonitrile and 0.05%formic acid in water.MS analysis was conducted in the multiple reaction monitoring mode,utilizing electrospray ionization in either the positive or negative mode,depending on the compound being analyzed.The method was validated for specificity,linearity,sensitivity,precision,accuracy,recovery,matrix effect,and stability,and found to be satisfactory.The validated method was then applied to a pharmacokinetic study in rat plasma following oral administration of DLP extract.Our findings revealed that all compounds were rapidly absorbed from the gastrointestinal tract into the plasma,with most being eliminated completely within 24 h.Notably,coumarins derived from Baizhi exhibited superior oral absorption effects compared to ligustilides from Chuanxiong.Furthermore,we observed that the elimination of coumarins from Baizhi within DLP was slower compared to their elimination in single Baizhi.These results provided valuable insights for the overall study of active substances within the DLP formula and further research into the interaction mechanisms of Baizhi-Chuanxiong compatibility.展开更多
A linear glucan was produced by Lactobacillus sake L-7 isolated from homemade sausage. Cultivation of the strain in Man–Rogosa–Sharpe(MRS) medium containing 50 g/L sucrose yielded 5.3 g/L of purified exopolysacchari...A linear glucan was produced by Lactobacillus sake L-7 isolated from homemade sausage. Cultivation of the strain in Man–Rogosa–Sharpe(MRS) medium containing 50 g/L sucrose yielded 5.3 g/L of purified exopolysaccharide(EPS). The EPS was characterized by gas chromatography(GC), Fourier-transform infrared(FT-IR) spectroscopy, high-performance sizeexclusion chromatography(HPSEC), nuclear magnetic resonance(NMR) spectroscopy, and scanning electron microscopy(SEM). The monosaccharide composition of the EPS was glucose, and its molecular weight was 1 × 10~7 Da. The FT-IR and NMR spectra revealed that the L-7 EPS was a linear glucan with α-(1 → 6) glucosidic bonds. SEM images of the dried EPS revealed a hollow tubular structure. The water solubility index and water holding capacity of L-7 EPS were 96 and 272%, respectively. The results of hydrolysis indicated that L-7 EPS was not susceptible to hydrolysis by physiological barriers and can be used as a soluble dietary fiber with health benefits. All these characteristics suggest that L-7 EPS might have potential applications in the food, cosmetic, and pharmaceutical industries.展开更多
A strain with high production of exopolysaccharide(EPS) was isolated from dried milk cake(a traditional fermented food from Inner Mongolia). The strain was called N21 and later identified as Leuconostoc citreum( Leu. ...A strain with high production of exopolysaccharide(EPS) was isolated from dried milk cake(a traditional fermented food from Inner Mongolia). The strain was called N21 and later identified as Leuconostoc citreum( Leu. citreum). The strain was cultured in Man-Rogosa-Sharpe medium containing 50 g/L of sucrose for 48 h at 30 °C and the EPS purified, with a yield of 24.5 g/L. An average molecular weight of 6.07 × 10~6 g/mol was determined by high-performance size-exclusion chromatography. The structure of the purified EPS was investigated through gas chromatography, ~1H and 13C nuclear magnetic resonance spectroscopy, and Fourier transform infrared spectroscopy. The results demonstrated a polysaccharide composed of D-glucopyranose units in a linear chain with consecutive α(1 → 6) linkages. No branching was found in the structure of the exopolysaccharide. The purified EPS showed high water solubility and emulsibility. Based on the thermogravimetric curve, the degradation temperature of the EPS was 308.47 °C, which suggested that the dextran in the study exhibited high thermal stability. The results indicated that Leu. citreum N21 could be widely used to produce linear EPS and that the EPS has potential applications in food science and processing as a food additive.展开更多
Taxol(Paclitaxel),an important anticancer drug,is derived at very low yields from Taxus(yew)species that grow very slowly.In the present study,thirteen genes that encode enzymes involved in Taxol biosynthesis in Taxus...Taxol(Paclitaxel),an important anticancer drug,is derived at very low yields from Taxus(yew)species that grow very slowly.In the present study,thirteen genes that encode enzymes involved in Taxol biosynthesis in Taxus spp.were analyzed with bioinformatics methods,and their expression levels in different tissues and after cold and hormone treatments were also analyzed.The results indicated that many cis-elements related to abiotic stresses and hormones were found in the promoter sequences of the 8 genes involved in Taxol biosynthesis.Moreover,the 13 enzymes encoded by the target genes were located in different organelles and had many phosphorylation sites in the response proteins.The 13 genes were expressed highly either in roots or in stems,with lower transcripts in needles,and they were highly expressed after treatment with cold,gibberellin,methyl jasmonate or coronatine,consistent with predictions based on the bioinformatics analysis.These results suggest that the factors such as hormones and abiotic stresses stimulate taxane biosynthesis in yews,providing an important way to sustainably generate taxanes from yew trees or their cell cultures to improve Taxol yields.展开更多
As one of the largest families of transcription factors(TFs)in plants,the WRKY TF family plays a key role in regulating plant responses to various biotic and abiotic stresses.However,there is no confirmed method to qu...As one of the largest families of transcription factors(TFs)in plants,the WRKY TF family plays a key role in regulating plant responses to various biotic and abiotic stresses.However,there is no confirmed method to quickly identify stress-responsive members from the WRKY gene family.In this study,all reported functional WRKY genes were first analyzed,and the amino acid patterns in response to stress were identified in group II-c(T-R/K-S/T-E/Q/D-V/I/L-E/D-I/V/H/N-L/M-D/E-D-G/E-F/Y-K/R-WRKYG-Q/K-K-A/T-VKN-S/N-P),group II-d(VPA-I/V-S-X-K-M/L/V/I-ADIP-P/A/V-D-D/EY/F-S-WRKYGQKPIKGSP-H/Y-PRGYYKCS-S/T-V/M-RGCPARKVER),and group II-e(PSD-S/A/L-WAWRKYGQKPIKGSPYPR-G/S-YYRCSSSKGC).WRKY genes in Dendrobium catenatum were used to validate the accuracy of these patterns.A total of 63 DcaWRKY genes were identified,their gene structures,conserved motifs,and gene expression patterns were analyzed,and a phylogenetic tree was constructed.Gene expression patterns were then analyzed under drought stress,and seven DcaWRKY genes(Dca002550,Dca002715,Dca005648,Dca007842,Dca010430,Dca016437,and Dca006787)were randomly selected to determine their expression levels and verify their expression patterns by quantitative real-time polymerase chain reaction analysis.The identified amino acid patterns were validated by drought-responsive WRKY genes in D.catenatum,confirming the accuracy of these amino acid patterns and providing valuable insights into further research of the WRKY family in D.catenatum.展开更多
With the development of superconducting technology, the electrical performance of insulating materials is drawing increasing concern. This paper is devoted to investigating resin materials and aims to test the resin r...With the development of superconducting technology, the electrical performance of insulating materials is drawing increasing concern. This paper is devoted to investigating resin materials and aims to test the resin requirements of impregnating procedures and design curing molds. First, the samples are prepared, and then the power-frequency breakdown, lighting surges, relative dielectric constant, and loss angle tangent of the impregnation resin are measured at room temperature and liquid nitrogen temperature. We also present the testing reference for cryogenic and high-voltage insulating materials of superconducting power devices.展开更多
Skin aging is characterized by a progressive decline in regenerative capacity,primarily driven by fibroblast senescence,oxidative stress,chronic inflammation,and the degradation of type Ⅰ/Ⅲ collagen,culminating in a...Skin aging is characterized by a progressive decline in regenerative capacity,primarily driven by fibroblast senescence,oxidative stress,chronic inflammation,and the degradation of type Ⅰ/Ⅲ collagen,culminating in an extracellular matrix(ECM)imbalance.Current injectable fillers—such as hyaluronic acid,collagen,and PLLA—provide temporary structural support but fail to address the underlying cellular senescence or restore ECM homeostasis,highlighting the need for regenerative biomaterials.Silk fibroin(SF),a natural protein,self-assembles into aβ-sheet-rich scaffold that structurally supports fibroblasts in depositing collagen and elastin,thereby improving the skin's ECM,accelerating wound healing,and promoting tissue regeneration.However,its role in modulating fibroblast senescence and ECM remodeling remains unclear.This study demonstrates that SF provides a suitable microenvironment for the adhesion and proliferation of fibroblasts,reducing the accumulation of SASP factors and facilitating the transition of fibroblasts from a senescent to a functional state.Furthermore,SF improves the skin microenvironment by reducing reactive oxygen species(ROS)and matrix metalloproteinase(MMP)expression through modulation of the ROS-MAPK-AP-1-MMP signal pathway,thereby delaying collagen degradation in aged skin.These findings reveal that SF uniquely rejuvenates fibroblasts and restores ECM homeostasis through a non-inflammatory mechanism,distinguishing it from conventional fillers that rely on inflammatory pathways for collagen induction.This work establishes SF as a next-generation injectable biomaterial with dual targeting of cellular senescence and ECM imbalance,offering a transformative strategy for regenerative dermatology and personalized anti-aging approaches.展开更多
基金financially supported by the Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences,China(Grant No.:2021-I2M-1-026)the National Natural Science Foundation of China(Grant No.:82304393)+1 种基金Beijing Natural Science Foundation,China(Grant No.:L242027)the National Key Research and Development Program of China(Grant No.:2023YFC2706100).
摘要This study presents the first development and validation of a static multiple light scattering(SMLS)-based method for real-time,non-invasive assessment of nanoparticle colloidal stability.Nanoparticles,leveraging their nanoscale advantages(e.g.,targeted delivery,enhanced drug solubility,and controlled release),hold transformative potential in treating diseases.However,their clinical success hinges on colloidal stability,which dictates in vivo behavior,safety,and regulatory compliance.While dynamic light scattering(DLS)remains widely used,its inability to monitor dynamic transformations and reliance on sample dilution limit its accuracy.Here,we pioneer the application of SMLS to systematically evaluate colloidal stability across standardized particles and commercial nanoparticle formulations(liposomes,nanoparticles,micelles,and nanoemulsions).Results demonstrate that SMLS captures destabilization kinetics(aggregation,sedimentation,and creaming)in real-time without dilution,even at high concentrations,while DLS fails to distinguish polydisperse systems due to time-point sampling.The Turbiscan stability index(TSI)quantifies instability mechanisms,correlating with particle size distribution broadening.This first comprehensive validation of SMLS for nanoparticles reveals its superiority in reflecting native-state behavior,exemplified by minimal or the variations in the average transmission(ΔT)or backscattering intensity(ΔBS)fluctuations and low TSI values in four commercial formulations.By addressing a critical technological gap,this study establishes SMLS as an indispensable tool for optimizing nanoparticle design,ensuring compliance with U.S.Food and Drug Administration(FDA)in-use stability guidelines,and accelerating clinical translation.
基金financial support from the CAMS Innovation Fund for Medical Sciences(CIFMS)(No.2021-I2M-1-026)。
摘要Compared to synthetic chemical compounds,plant extracts derived from natural sources have emerged as the"new favorites"in the treatment and care of skin diseases due to their distinct advantages,including being environmentally friendly,sustainable,and safe.However,challenges such as poor solubility,limited permeability,and the barrier function of the stratum corneum significantly restrict the application of natural products in dermal drug delivery.Fortunately,advancements in nanotechnology offer promising solutions to overcome these challenges.Different skin diseases and treatments require the precise delivery of natural active ingredients to specific skin layers,and the unique structure of nanocarriers enables targeted delivery to achieve desired therapeutic outcomes.This paper begins by exploring the pathogenesis and therapeutic targets of common skin conditions,including atopic dermatitis(AD),psoriasis,decubitus ulcers,diabetic foot ulcers(DFUs),as well as applications in antioxidant therapies and anti-aging strategies.Furthermore,it provides a detailed overview of the depths and locations within the skin where active compounds must be delivered to exert their effects effectively.Subsequently,this review categorizes and examines natural products based on their therapeutic effects on various skin diseases.It then highlights the skin depths and specific sites that can be targeted by different delivery systems designed to enhance skin permeability,tailored to meet the needs of skin disease treatment or care.By addressing these aspects,this review aims to provide a valuable reference for advancing research on nano-delivery systems in the field of topical skin drug delivery for the treatment and management of skin diseases.
基金financially supported by National Natural Science Foundation(No.82304393)Beijing Natural Science Foundation(Nos.L242027 and L256067,China)+2 种基金CAMS Innovation Fund for Medical Sciences(No.2025-I2M-XHXX-093)National Key R&D Program(No.2023YFC2706100)Beijing Nova Program(No.20250484812)。
摘要Skin aging is a multifactorial biological process driven by oxidative stress(OS),chronic inflammation,cellular senescence,mitochondrial dysfunction,and non-enzymatic glycation(NEG),and is markedly accelerated by environmental stressors such as ultraviolet radiation(UVR)and air pollution.Natural bioactive compounds,including flavonoids,polyphenols,terpenoids,alkaloids,vitamins,polysaccharides,peptides,and indole derivatives,have demonstrated considerable potential in mitigating these processes through multi-target antioxidant,anti-inflammatory,anti-photoaging,and extracellular matrix(ECM)-protective mechanisms.However,their clinical and cosmetic translation is often limited by poor solubility,chemical instability,and insufficient skin penetration.Rather than providing a simple compilation of existing studies,this review offers a mechanism-oriented and delivery-driven synthesis of recent advances in natural anti-skin-aging research.We systematically integrate current knowledge on the molecular drivers of skin aging with a critical comparison of emerging transdermal and nanotechnology-based delivery systems,including lipid-based,polymer-based,inorganic/hybrid,and nucleic acid-assembled nanocarriers.Particular attention is given to how rational carrier design modulates stability,permeability,skin-layer targeting,and controlled release behavior.Furthermore,this review critically discusses current limitations,contradictory findings across studies,and key translational challenges,and identifies promising future research directions,such as stimuli-responsive systems,skin-layer-specific targeting,and mechanism-guided material selection.By bridging biological mechanisms with delivery material innovation,this work provides a forward-looking framework for the development of safer,more effective,and scientifically grounded anti-skin-aging therapeutics and cosmeceuticals.
基金supported by the National Natural Science Foundation of China(Nos.82373624 and 82160630)the Natural Science Foundation of Inner Mongolia(No.2023LHMS08010)STU Scientific Research Initiation Grant provided financial support for this research(No.NTF25006T).
摘要Cadmium(Cd),a pervasive environmental heavy metal pollutant,has been extensively documented for its toxic effects on human health.However,the underlying pathogenic mechanisms of Cd toxicity,spanning molecular to cellular levels,remain incompletely elucidated and warrant further investigation.Here,quantitative real-time PCR(qRT-PCR)and enzyme-linked immunosorbent assay(ELISA)analyses demonstrated that cadmium exposure induced a pronounced inflammatory response,characterized by significant elevation of interleukin-6(IL-6)and interleukin-8(IL-8)in 16HBE cells.High-throughput sequencing of cadmium-exposed versus control 16HBE cells identified LncPOPDC3-1 as a novel differentially expressed transcript showing marked upregulation during cadmium-triggered inflammation.We found that LncPOPDC3-1 accelerated the progression of inflammation,including increasing inflammatory factors IL-6 and IL-8.Mechanistically,dual luciferase reporter gene assays and qRT-PCR analysis have demonstrated that LncPOPDC3-1 can directly bind to miR-548a-3p,which regulated the activation of NF-κB signaling pathway.Following inhibition of the NF-κB signaling pathway,the regulatory effect of LncPOPDC3-1 on Cd-induced inflammation was significantly attenuated.Therefore,our data suggest that LncPOPDC3-1 regulates the activation of NF-κB pathway through competitive bound to miR-548a-3p,which subsequently promotes the Cd-induced inflammation in 16HBE cells.This provides a new mechanism and potential molecular targets for Cd-induced toxicity.
基金supported by the National Natural Science Foundation of China(Grant Nos.82472973,82030092,82273362,82272680,and 82103006)the National Key Research and Development Program of China(Grant No.2021YFA1201100)+2 种基金the Tianjin Natural Science Foundation(Grant Nos.19JCJQJC63100 and 22JCQNJC00100)the Science&Technology Development Fund of Tianjin Education Commission for Higher Education(Grant No.2022KJ221)the Tianjin Key Medical Discipline(Specialty)Construction Project(Grant No.TJYXZDXK-009A).
摘要Objective:CLT-003 is a novel phenylphthalimide derivative encapsulated in poly(lactate-glycolic acid)copolymer nanoparticles using nanotechnology techniques.CLT-003 possesses anti-angiogenetic and antitumor activities.Nevertheless,the role and molecular mechanism underlying CLT-003 in pancreatic cancer remain to be elucidated.Methods:Cell proliferation and apoptosis were detected using CCK-8,real-time cell analysis(RTCA),EdU,and flow cytometric assays.Cellular mobility and invasive capacity were detected using wound-healing,Transwell,and cell motility assays.Tumor growth and metastasis were determined using the mouse subcutaneous and pancreatic cancer orthotopic liver metastasis models.The antitumor effects of CLT-003 were evaluated using patient-derived organoid(PDO)and patient-derived xenograft(PDX)models.Results:CLT-003 significantly inhibited cellular proliferation,enhanced cellular apoptosis,and attenuated cellular invasion and migration of pancreatic cancer cells.Mechanistically,CLT-003 suppressed the translation of HIF-1a by inhibiting the PI3K/AKT/mTOR signaling pathway.In the mouse tumor models,CLT-003 significantly inhibited the growth and metastasis of pancreatic tumors.Moreover,the PDO and PDX models showed increased sensitivity to CLT-003 in pancreatic cancer with high HIF-1α expression compared to pancreatic cancer with low HIF-1a expression.Conclusions:This study delineated the role and molecular mechanism of CLT-003 action in impeding the progression of pancreatic cancer and indicated its robust potential for the treatment of pancreatic cancer.
基金supported by the grants from the CAMS Innovation Fund for Medical Sciences(CIFMS)(Grant No.:2021-I2M-1-026)the Beijing Natural Science Foundation of China(Grant Nos.:7212155 and 7162135).
摘要Obesity and related metabolic syndromes have been recognized as important disease risks,in which the role of adipokines cannot be ignored.Adiponectin(ADP)is one of the key adipokines with various beneficial effects,including improving glucose and lipid metabolism,enhancing insulin sensitivity,reducing oxidative stress and inflammation,promoting ceramides degradation,and stimulating adipose tissue vascularity.Based on those,it can serve as a positive regulator in many metabolic syndromes,such as type 2 diabetes(T2D),cardiovascular diseases,non-alcoholic fatty liver disease(NAFLD),sarcopenia,neurodegenerative diseases,and certain cancers.Therefore,a promising therapeutic approach for treating various metabolic diseases may involve elevating ADP levels or activating ADP receptors.The modulation of ADP genes,multimerization,and secretion covers the main processes of ADP generation,providing a comprehensive orientation for the development of more appropriate therapeutic strategies.In order to have a deeper understanding of ADP,this paper will provide an all-encompassing review of ADP.
基金National Nature Science Foundation of China(Grant Nos.81503208,81403068,30672609)Beijing Municipal Natural Science Foundation(Grant No.7144219)National Key Technology R&D Program of China(Grant No.2011BAI07B08)
摘要Angelicae Pubescentis Radix(APR,Duhuo)is a commonly used traditional Chinese medicine and usually used for the treatments of rheumatic diseases.To assess the chemical composition of APR extract,a sensitive and reliable UPLC-Q-TOF-MS method was used for qualitative analysis.The separation was achieved on an Agilent SB-C18 column(1.8μm,2.1 mm×50 mm)with a gradient elution system consisting of acetonitrile and water containing 0.1%formic acid.An electrospray ionization(ESI)was used for mass spectrometer,and the data were collected in the positive ion mode,which was operated in a full-scan mode at m/z 100-800.A total of 49 compounds including 46 coumarins were identified according to the MS and MS/MS data.Among them,two were new compounds,and isoangenomalin,scoparone,4-methyl-umbelliferyl acetate,suberenol,trans-dehydroosthol,and oroselone were first reported in APR.
基金financially supported by Beijing Nova Program(Nos.Z211100002121127 and 20220484219)Beijing Natural Science Foundation(No.L212059)+1 种基金Fundamental Research Funds for the Central Universities(No.3332021101)CAMS Innovation Fund for Medical Sciences(CIFMS,Nos.2021-I2M-1-026 and 2021-I2M-1-028).
摘要Ulcerative colitis(UC)is a common progressive inflammatory disease whose incidence has increased rapidly in recent years,and can develop into colorectal cancer in severe cases.There are currently no adequate or effective treatments for UC due to the fact that some patients have found suboptimal results after repeated administration,while others have experienced adverse effects.With the rapid development of nanotechnology,developing innovative colon-targeting platforms is essential to improving efficacy,reducing side effects,and improving patient compliance.In this review,we summarize the pathophysiological characteristics of UC and the most recent status of numerous nanodrug delivery systems based on different targeting mechanisms in treating UC.Oral,intravenous,and rectal drug delivery nanoparticles targeting the colon are discussed,which can provide ideas for the design of colon-targeting nanoparticles for the treatment of colon diseases,especially for the treatment of UC.Last but not least,we provide a glimpse into the future of colon-targeted delivery systems,as well as future advancements in the field.
基金supported by the National Science and Technology Major Project of China(Grant No.:2018ZX09711001)Beijing Nova Program(Grant No.:Z211100002121127)+2 种基金Beijing Natural Science Foundation(Grant No.:L212059)Fundamental Research Funds for the Central Universities(Grant No.:3332021101)CAMS Innovation Fund for Medical Sciences(CIFMS,Grant No.:2022-I2M-JB-011).
摘要Lipid nanoemulsions are promising nanodrug delivery carriers that can improve the efficacy and safety of paclitaxel(PTX).However,no intravenous lipid emulsion of PTX has been approved for clinical treatment,and systemic safety profiles have not yet been reported.Here we outline the development of a PTXloaded tumor-targeting intravenous lipid emulsion(PTX Emul)and describe its characteristics,colloidal stability,and systemic safety profiles in terms of acute toxicity,long-term toxicity,and toxicokinetics.We also compare PTX Emul with conventional PTX injection.Results showed that PTX Emul exhibited an ideal average particle size(approximately 160 nm)with narrow size distribution and robust colloidal stability under different conditions.Hypersensitivity reaction and hemolysis tests revealed that PTX Emul did not induce hypersensitivity reactions and had no hemolytic potential.In addition,where the alleviated systemic toxicity of PTX Emul may be attributed to the altered toxicokinetic characteristics in beagle dogs,including the decreased AUC and increased plasma clearance and volume of distribution,PTX Emul alleviated acute and long-term toxicity as evidenced by the enhanced the median lethal dose and approximate lethal dose,moderate body weight change,decreased bone marrow suppression and organ toxicity compared with those under PTX injection at the same dose.A fundamental understanding of the systemic safety profiles,high tumor-targeting efficiency,and superior antitumor activity in vivo of PTX Emul can provide powerful evidence of its therapeutic potential as a future treatment for breast cancer.
基金National Natural Science Foundation of China(Grant No.81773865)the National Key R&D Program of China(Grant No.2018YFC1704500,2018YFC1704506)。
摘要Evodiamine,rutaecarpine,and dehydroevodiamine have been demonstrated as the major alkaloids in the fruits of Euodia rutaecarpa,a well-known traditional Chinese medicine with central nervous system activities.To study their cerebrospinal fluid pharmacokinetics and cerebral nuclei distribution,the alkaloids were mixed at the weight ratio of 1:1:1 and orally administered via gavage to the rats at each dose of 15 mg/kg.A quick and reliable ultra-performance liquid chromatographic-tandem mass spectrometry method was developed and applied for the simultaneous analysis of the alkaloids in rat cerebrospinal fluid and cerebral nuclei collected at different time points.Non-compartmental pharmacokinetic profiles were calculated,and the distribution in cerebral nuclei was compared.All the tested compounds were absorbed into rat cerebrospinal fluid and distributed to the brain nuclei quickly.Their distribution in different nuclei varied,as evodiamine mainly in cerebellum and brainstem,rutaecarpine with its maximum in the brainstem,and dehydroevodiamine mostly in the cerebellum and hippocampus.They were eliminated from the brain rapidly without long-time accumulation.In summary,this study revealed the targeting discrepancy of evodiamine,rutaecarpine,and dehydroevodiamine in the brain,and highlighted the possibility for drug candidates in the encephalopathy treatment of the fruits of E.rutaecarpa.
基金financially supported by the National Natural Science Foundation(No.82304393,China)Beijing Nova Program(Nos.Z211100002121127 and 20220484219,China)+1 种基金Beijing Natural Science Foundation(No.L212059,China)CAMS Innovation Fund for Medical Sciences(No.2021-I2M-1-028,China)。
摘要Ulcerative colitis(UC)is a chronic inflammatory bowel disease characterized by persistent inflammation of the colon and disrupted intestinal function.Ramulus mori(Sangzhi)alkaloids(SZ-A),derived from twigs of mulberry,were approved by the National Medical Products Administration in 2020 for treating type 2 diabetes mellitus.Accumulated evidence has confirmed that SZ-A also alleviates non-alcoholic fatty liver disease and ameliorates inflammation,indicating its potential to address inflammation in UC.However,the treatment of UC faces challenges due to low drug delivery efficiency and short retention time.To overcome these challenges,an injectable and adherent in-situ thermo-sensitive hydrogel containing SZ-A was developed for rectal drug delivery,utilizing the thermo-sensitive polymers Poloxamer 407and 188.The thermo-sensitive hydrogel system was designed with a moderate gelation temperature of 32±0.5℃,a short gelation time of 64 s,a p H range of 7-10,high moisturizing capability exceeding 90%,and moderate mechanical strength of 4-5 s.In a rat model with UC,the in situ thermo-sensitive hydrogel significantly extended the retention time at the colonic site and enabled sustained release after rectal administration.Symptoms of UC were markedly reduced following rectal administration of SZ-A thermosensitive hydrogel.Furthermore,the release of inflammatory factors,such as interleukin-1β(IL-1β),IL-6,IL-18,tumor necrosis factor-α(TNF-α),and transforming growth factor-β1(TGF-β1),significantly decreased in the SZ-A thermo-sensitive hydrogel group.The integrity of the colonic mucosal barrier was significantly enhanced following the application of SZ-A thermo-sensitive hydrogel.In conclusion,rectal administration of SZ-A in situ thermo-sensitive hydrogel effectively alleviated UC symptoms,inhibited the secretion of inflammatory factors,and promoted the repair of the colonic mucosal barrier.This approach holds promise as a potential treatment for UC.
基金National Natural Science Foundation of China(Grant No.81473321)Beijing Natural Sciences Foundation(Grant No.7152086)。
摘要Duliang Pill(DLP),consisting of Baizhi and Chuanxiong,is the classical formula of traditional Chinese medicine.In order to investigate the substance basis of DLP,we developed a highly sensitive and reliable UPLC-MS/MS method capable of simultaneously detecting 37 constituents from both Baizhi and Chuanxiong.To achieve chromatographic separation,we utilized a Diamonsil C18column along with a mobile phase consisting of acetonitrile and 0.05%formic acid in water.MS analysis was conducted in the multiple reaction monitoring mode,utilizing electrospray ionization in either the positive or negative mode,depending on the compound being analyzed.The method was validated for specificity,linearity,sensitivity,precision,accuracy,recovery,matrix effect,and stability,and found to be satisfactory.The validated method was then applied to a pharmacokinetic study in rat plasma following oral administration of DLP extract.Our findings revealed that all compounds were rapidly absorbed from the gastrointestinal tract into the plasma,with most being eliminated completely within 24 h.Notably,coumarins derived from Baizhi exhibited superior oral absorption effects compared to ligustilides from Chuanxiong.Furthermore,we observed that the elimination of coumarins from Baizhi within DLP was slower compared to their elimination in single Baizhi.These results provided valuable insights for the overall study of active substances within the DLP formula and further research into the interaction mechanisms of Baizhi-Chuanxiong compatibility.
基金supported by National Science and Technology Support Program of China (No. 2015BAD16B01)
摘要A linear glucan was produced by Lactobacillus sake L-7 isolated from homemade sausage. Cultivation of the strain in Man–Rogosa–Sharpe(MRS) medium containing 50 g/L sucrose yielded 5.3 g/L of purified exopolysaccharide(EPS). The EPS was characterized by gas chromatography(GC), Fourier-transform infrared(FT-IR) spectroscopy, high-performance sizeexclusion chromatography(HPSEC), nuclear magnetic resonance(NMR) spectroscopy, and scanning electron microscopy(SEM). The monosaccharide composition of the EPS was glucose, and its molecular weight was 1 × 10~7 Da. The FT-IR and NMR spectra revealed that the L-7 EPS was a linear glucan with α-(1 → 6) glucosidic bonds. SEM images of the dried EPS revealed a hollow tubular structure. The water solubility index and water holding capacity of L-7 EPS were 96 and 272%, respectively. The results of hydrolysis indicated that L-7 EPS was not susceptible to hydrolysis by physiological barriers and can be used as a soluble dietary fiber with health benefits. All these characteristics suggest that L-7 EPS might have potential applications in the food, cosmetic, and pharmaceutical industries.
基金supported by the National Science and Technology Support Plan Project(No.2015BAD16B01)
摘要A strain with high production of exopolysaccharide(EPS) was isolated from dried milk cake(a traditional fermented food from Inner Mongolia). The strain was called N21 and later identified as Leuconostoc citreum( Leu. citreum). The strain was cultured in Man-Rogosa-Sharpe medium containing 50 g/L of sucrose for 48 h at 30 °C and the EPS purified, with a yield of 24.5 g/L. An average molecular weight of 6.07 × 10~6 g/mol was determined by high-performance size-exclusion chromatography. The structure of the purified EPS was investigated through gas chromatography, ~1H and 13C nuclear magnetic resonance spectroscopy, and Fourier transform infrared spectroscopy. The results demonstrated a polysaccharide composed of D-glucopyranose units in a linear chain with consecutive α(1 → 6) linkages. No branching was found in the structure of the exopolysaccharide. The purified EPS showed high water solubility and emulsibility. Based on the thermogravimetric curve, the degradation temperature of the EPS was 308.47 °C, which suggested that the dextran in the study exhibited high thermal stability. The results indicated that Leu. citreum N21 could be widely used to produce linear EPS and that the EPS has potential applications in food science and processing as a food additive.
基金This work was supported by National Natural Science Foundation of China(31570675)a Grant from the National Key Research and Development Program of China(2017YFD060070605)a Grant for National non-profit Research Institutions of Chinese Academy of Forestry(CAFYBB2018SY009).
摘要Taxol(Paclitaxel),an important anticancer drug,is derived at very low yields from Taxus(yew)species that grow very slowly.In the present study,thirteen genes that encode enzymes involved in Taxol biosynthesis in Taxus spp.were analyzed with bioinformatics methods,and their expression levels in different tissues and after cold and hormone treatments were also analyzed.The results indicated that many cis-elements related to abiotic stresses and hormones were found in the promoter sequences of the 8 genes involved in Taxol biosynthesis.Moreover,the 13 enzymes encoded by the target genes were located in different organelles and had many phosphorylation sites in the response proteins.The 13 genes were expressed highly either in roots or in stems,with lower transcripts in needles,and they were highly expressed after treatment with cold,gibberellin,methyl jasmonate or coronatine,consistent with predictions based on the bioinformatics analysis.These results suggest that the factors such as hormones and abiotic stresses stimulate taxane biosynthesis in yews,providing an important way to sustainably generate taxanes from yew trees or their cell cultures to improve Taxol yields.
基金supported by the Young Talent Project of Hebei Agricultural University Foundation(YJ201848)the Youth Fund of Hebei Province Natural Science Foundation(C2019204295)。
摘要As one of the largest families of transcription factors(TFs)in plants,the WRKY TF family plays a key role in regulating plant responses to various biotic and abiotic stresses.However,there is no confirmed method to quickly identify stress-responsive members from the WRKY gene family.In this study,all reported functional WRKY genes were first analyzed,and the amino acid patterns in response to stress were identified in group II-c(T-R/K-S/T-E/Q/D-V/I/L-E/D-I/V/H/N-L/M-D/E-D-G/E-F/Y-K/R-WRKYG-Q/K-K-A/T-VKN-S/N-P),group II-d(VPA-I/V-S-X-K-M/L/V/I-ADIP-P/A/V-D-D/EY/F-S-WRKYGQKPIKGSP-H/Y-PRGYYKCS-S/T-V/M-RGCPARKVER),and group II-e(PSD-S/A/L-WAWRKYGQKPIKGSPYPR-G/S-YYRCSSSKGC).WRKY genes in Dendrobium catenatum were used to validate the accuracy of these patterns.A total of 63 DcaWRKY genes were identified,their gene structures,conserved motifs,and gene expression patterns were analyzed,and a phylogenetic tree was constructed.Gene expression patterns were then analyzed under drought stress,and seven DcaWRKY genes(Dca002550,Dca002715,Dca005648,Dca007842,Dca010430,Dca016437,and Dca006787)were randomly selected to determine their expression levels and verify their expression patterns by quantitative real-time polymerase chain reaction analysis.The identified amino acid patterns were validated by drought-responsive WRKY genes in D.catenatum,confirming the accuracy of these amino acid patterns and providing valuable insights into further research of the WRKY family in D.catenatum.
基金supported by the State Grid Scientific and Technological Project (Research on New Cryogenic Insulating Material and Superconducting Magnet Application,No.DG71-16-001)
摘要With the development of superconducting technology, the electrical performance of insulating materials is drawing increasing concern. This paper is devoted to investigating resin materials and aims to test the resin requirements of impregnating procedures and design curing molds. First, the samples are prepared, and then the power-frequency breakdown, lighting surges, relative dielectric constant, and loss angle tangent of the impregnation resin are measured at room temperature and liquid nitrogen temperature. We also present the testing reference for cryogenic and high-voltage insulating materials of superconducting power devices.
基金supported by National Natural Science Foundation(Nos.82304393 and 52171237)CAMS Innovation Fund for Medical Sciences(No.2025-I2M-XHXX-093)+3 种基金Beijing Natural Science Foundation(Nos.L242027 and L256067,China)Non-profit central research institute fund of national research for family planning(No.2025GJZD01)National Key R&D Program(2023YFC2706100)Beijing Nova Program(No.20250484812).
摘要Skin aging is characterized by a progressive decline in regenerative capacity,primarily driven by fibroblast senescence,oxidative stress,chronic inflammation,and the degradation of type Ⅰ/Ⅲ collagen,culminating in an extracellular matrix(ECM)imbalance.Current injectable fillers—such as hyaluronic acid,collagen,and PLLA—provide temporary structural support but fail to address the underlying cellular senescence or restore ECM homeostasis,highlighting the need for regenerative biomaterials.Silk fibroin(SF),a natural protein,self-assembles into aβ-sheet-rich scaffold that structurally supports fibroblasts in depositing collagen and elastin,thereby improving the skin's ECM,accelerating wound healing,and promoting tissue regeneration.However,its role in modulating fibroblast senescence and ECM remodeling remains unclear.This study demonstrates that SF provides a suitable microenvironment for the adhesion and proliferation of fibroblasts,reducing the accumulation of SASP factors and facilitating the transition of fibroblasts from a senescent to a functional state.Furthermore,SF improves the skin microenvironment by reducing reactive oxygen species(ROS)and matrix metalloproteinase(MMP)expression through modulation of the ROS-MAPK-AP-1-MMP signal pathway,thereby delaying collagen degradation in aged skin.These findings reveal that SF uniquely rejuvenates fibroblasts and restores ECM homeostasis through a non-inflammatory mechanism,distinguishing it from conventional fillers that rely on inflammatory pathways for collagen induction.This work establishes SF as a next-generation injectable biomaterial with dual targeting of cellular senescence and ECM imbalance,offering a transformative strategy for regenerative dermatology and personalized anti-aging approaches.