Ultrasonic humidifiers are commonly used in households to maintain indoor humidity and generate a large number of droplets or spray aerosols.However,there have been various health concerns associated with humidifier u...Ultrasonic humidifiers are commonly used in households to maintain indoor humidity and generate a large number of droplets or spray aerosols.However,there have been various health concerns associated with humidifier use,largely due to aerosols generated during operation.Here,we investigated the size distribution,chemical composition,and charged fraction of aerosol particles emitted from commercial ultrasonic humidifiers.Heavy metals in water used for humidifiers were found to be highly enriched in the ultrasonic humidifier aerosols(UHA),with the enrichment factors ranging from 102 to 107.This enrichment may pose health concerns for the building occupants,as UHA concentrations of up to 106 particles/cm^(3) or 3 mg/m^(3) were observed.Furthermore,approximately 90%of UHA were observed to be electrically charged,for the first time according to our knowledge.Based on this discovery,we proposed and tested a newmethod to remove UHA by using a simple electrical field.The designed electrical field in this work can efficiently remove 81.4%of UHA.Therefore,applying this electrical field could be an effective method to significantly reduce the health risks by UHA.展开更多
As immunotherapy has gained increasing interest as a new foundation for cancer therapy,some atypical response patterns,such as pseudoprogression and hyperprogression,have garnered the attention of physicians.Pseudopro...As immunotherapy has gained increasing interest as a new foundation for cancer therapy,some atypical response patterns,such as pseudoprogression and hyperprogression,have garnered the attention of physicians.Pseudoprogression is a phenomenon in which an initial increase in tumor size is observed or new lesions appear,followed by a decrease in tumor burden;this phenomenon can benefit patients receiving immunotherapy but often leads to premature discontinuation of treatment owing to the false judgment of progression.Accurately recognizing pseudoprogression is also a challenge for physicians.Because of the extensive attention on pseudoprogression,significant progress has been made.Some new criteria for immunotherapy,such as irRC,iRECIST and imRECIST,were proposed to accurately evaluate the response to immunotherapy.Many new detection indexes,such as ctDNA and IL-8,have also been used to identify pseudoprogression.In this review,the definition,evaluation criteria,mechanism,monitoring,management and prognosis of pseudoprogression are summarized,and diagnostic and treatment processes for patients with progression but with a suspicion of pseudoprogression are proposed;these processes could be helpful for physicians in clinical practice and enhances the understanding of pseudoprogression.展开更多
Photocatalytic reduction of CO_(2) is considered as a kind of promising technologies for solving the greenhouse effect.Herein,a novel hybrid structure of g-C_(3)N_(4)/ZnO/Ti_(3)C_(2) photocatalysts was designed and fa...Photocatalytic reduction of CO_(2) is considered as a kind of promising technologies for solving the greenhouse effect.Herein,a novel hybrid structure of g-C_(3)N_(4)/ZnO/Ti_(3)C_(2) photocatalysts was designed and fabricated to investigate their abilities for CO_(2) reduction.As demonstration,heterojunction of g-C_(3)N_(4)/ZnO can improve photogenerated carriers’separation,the addition of Ti_(3)C_(2) fragments can further facilitate the photocatalytic performance from CO_(2) to CO.Hence,g-C_(3)N_(4)/ZnO/Ti_(3)C_(2) has efficiently increased CO production by 8 and 12 times than pristine g-C_(3)N_(4) and ZnO,respectively.Which is ascribed to the photogenerated charge migration promoted by metallic Ti_(3)C_(2).This work provides a guideline for designing efficient hybrid catalysts on other applications in the renewable energy fields.展开更多
Extracellular vesicles(EVs)are nano-sized bilayer vesicles that are shed or secreted by virtually every cell type.A variety of biomolecules,including proteins,lipids,coding and non-coding RNAs,and mitochondrial DNA,ca...Extracellular vesicles(EVs)are nano-sized bilayer vesicles that are shed or secreted by virtually every cell type.A variety of biomolecules,including proteins,lipids,coding and non-coding RNAs,and mitochondrial DNA,can be selectively encapsulated into EVs and delivered to nearby and distant recipient cells,leading to alterations in the recipient cells,suggesting that EVs play an important role in intercellular communication.EVs play effective roles in physiology and pathology and could be used as diagnostic and therapeutic tools.At present,although the mechanisms of exosome biogenesis and secretion in donor cells are well understood,the molecular mechanism of EV recognition and uptake by recipient cells is still unclear.This review summarizes the current understanding of the molecular mechanisms of EVs’biological journey in recipient cells,from recognition to uptake and cargo release.Furthermore,we highlight how EVs escape endolysosomal degradation after uptake and thus release cargo,which is crucial for studies applying EVs as drug-targeted delivery vehicles.Knowledge of the cellular processes that govern EV uptake is important to shed light on the functions of EVs as well as on related clinical applications.展开更多
Dietary meats play a crucial role in human health. The objective of this survey was to determine the fatty acid content and omega-6/omega-3 polyunsaturated fatty acids （n-6/n-3 PUFA） ratio of fresh red meat （beef a...Dietary meats play a crucial role in human health. The objective of this survey was to determine the fatty acid content and omega-6/omega-3 polyunsaturated fatty acids （n-6/n-3 PUFA） ratio of fresh red meat （beef and pork） from four cities （Shanghai, Nanjing, Yinchuan and Hohhot） in China. The results showed that the n-6/n-3 PUFA ratio from all the samples ranged from 6 to 23. The total n-6 PUFA concentrations ranged from 290.54 mg/100 g in beef from Nanjing to 1601.48 mg/100 g in pork from Hohhot, whereas the total concentrations of n-3 PUFA ranged from 46.34 mg/100 g in beef from Nanjing to 96.03 mg/100 g in pork from Nanjing. The results indicated that the n-6/n-3 ratio in the red meat from all four regions is unbalanced and is much higher than that （〈 5：1） rec- ommended by the WHO/FAO. The total amount of n-3 PUFA was far lower than the required daily dose. There- fore, potential solutions to increase the n-3 PUFA content in meat products or to provide alternative source of n-3 PUFA should be explored.展开更多
Oleanolic acid(OA) and echinocystic acid(EA), two naturally occurring pentacyclic oleanane triterpenes,are gaining increasing attention due to their promising pharmacological activities. Conjugation with amphiphilic ...Oleanolic acid(OA) and echinocystic acid(EA), two naturally occurring pentacyclic oleanane triterpenes,are gaining increasing attention due to their promising pharmacological activities. Conjugation with amphiphilic α(β)-cyclodextrin(CD) via "click chemistry" can improve their solubility and anti-HCV entry potency. In the present work,four water-soluble β-CD-pentacyclic triterpene conjugates were designed and synthesized, in which OA and EA was coupled to one of the primary hydroxyl groups of β-CD via ester and amide bonds. The structures of the conjugates were unambiguously determined by ~1H NMR, ^(13)C NMR and HRMS or MALDI-TOF-MS. All the conjugates showed lower hydrophobicity(AlogP) than their parent compounds and no significant cytotoxicity was found to HL-60, A549, Hela and Bel-7402 cells at concentrations up to 10 μmol/L. Further anti-HCV entry activity and mechanism studies are under way in our laboratory.展开更多
Objective:In this study,we aimed to identify novel genetic loci and protein biomarkers associated with silicosis susceptibility in Chinese workers through integrated proteomic and genomic analyses and to develop an ea...Objective:In this study,we aimed to identify novel genetic loci and protein biomarkers associated with silicosis susceptibility in Chinese workers through integrated proteomic and genomic analyses and to develop an early diagnostic prediction model.Methods:A genome-wide association study(GWAS)was conducted on 163 patients with silicosis and 183 controls,followed by Olink proteomic profiling of 92 plasma proteins.Protein quantitative trait loci(pQTL)mapping,Mendelian randomization(MR),and Bayesian co-localization were used to infer causal relationships.A causal protein risk score(CPRS)model integrating genetic and proteomic data was developed and validated using 10-fold cross-validation.Results:GWAS identified 16 novel risk loci(P<1×10^(-5)),including rs6677666(WLS)and rs2272528(COL4A4).MR analysis revealed eight plasma proteins associated with silicosis risk,with MMP12,EGF,Gal_9,GZMA,and ICOSLG showing significant differential expression(P<0.05).The CPRS model combining these proteins demonstrated a high diagnostic accuracy(AUC=0.915),outperforming traditional clinical variables.Conclusion:This multi-omics study uncovered genetic and proteomic markers linked to silicosis susceptibility and established a robust predictive model.The integration of GWAS and proteomics offers novel insights into the pathogenesis of silicosis,and supports development of early detection and prevention policies for high-risk populations.展开更多
Congenital deficiency or extensive cervical injury leads to female genital tract obstruction and cervical laxity,resulting in infertility or miscarriage.Current clinical approaches could be conducted to restore the co...Congenital deficiency or extensive cervical injury leads to female genital tract obstruction and cervical laxity,resulting in infertility or miscarriage.Current clinical approaches could be conducted to restore the continuity of cervix.However,full-thickness and large-scale cervical regeneration with complete structural and functional restoration have not been reported.In this study,we fabricated a double-layered collagen membrane(CM)scaffold based on decellularized extracellular matrix.Each layer was adapted to support the growth of epithelial cells and stromal cells,respectively.Further,the thickness and folded“sandwich”structure were tailored to match the cervical structure.When transplanted into rabbit full-thickness and total ectocervix excision models,only CM scaffold groups enabled the regeneration of neo-ectocervix tissue,including epithelium,stroma and muscular layers after 3 and 6 months.The neo-ectocervix regenerated by CM scaffolds exhibited significantly higher expression of secretory glands and estrogen receptors,more secretion of neutral and acidic mucins,showing functional maturity of regenerated epithelium.Notably,CM scaffolds supported the regeneration of stroma and muscular layers.The mechanical strength of neo ectocervix was comparable to that of normal ectocervix.CM scaffolds demonstrate good biocompatibility,support different cell growth,and enhance superior regeneration of epithelium,stromal and muscular tissue,confirming its construction capacity as new strategies for addressing cervical deficiency and damage.展开更多
Exploring exogenous additives to enhance non-protein energy ingredient utilization in fish is highly anticipated.Epigallocatechin-3-gallate(EGCG)is a prominent polyphenol found in green tea.To assess the regulatory ef...Exploring exogenous additives to enhance non-protein energy ingredient utilization in fish is highly anticipated.Epigallocatechin-3-gallate(EGCG)is a prominent polyphenol found in green tea.To assess the regulatory effect of EGCG on metabolic disorders induced by an excess of non-protein energy sources in grass carp(Ctenopharyngodon idella),five isonitrogenous diets were formulated:a control diet(23% digestible carbohydrates,4.7% crude lipids),a high-carbohydrate(HC;48% digestible carbohydrates,4.7% crude lipids)diet,a high-fat(HF;23% digestible carbohydrates,9.6% crude lipid)diet,the HC diet supplemented with 0.05% EGCG(HC+EGCG)and the HF diet supplemented with 0.05% EGCG(HF+EGCG).The diets were fed to 450 fish(initial body weight=8.50 g)in three replicates for eight weeks.After the feeding trial,compared with the control group,EGCG significantly alleviated the growth suppression induced by HC or HF intake(P<0.05).Dietary EGCG supplementation downregulated the expression of fatty acid synthesis genes(srebp1,acc,and fas)(P<0.05).Further,EGCG supplementation to the HC diet significantly increased hepatic glycogen synthesis and suppressed elevated glucose concentration through gluconeogenesis(P<0.05).Additionally,EGCG supplementation significantly reduced excess circulating glucose by inhibiting α-amylase activities and decreasing the expression of glucose transporter 2(glut2)in the intestines of grass carp(P<0.05).Furthermore,in order to reveal the mechanism of EGCG affecting feeding and metabolism,transcriptome analysis on grass carp hepatocytes was conducted.The results showed that the leptin b(lepb)and G protein-coupled bile acid receptor 1(gpbar1)were key candidate genes among differentially expressed genes from the cell transcriptome.Further in vivo studies found that the high leptin release induced by EGCG may play a pivotal role in the regulation of feed intake and appetite.Moreover,through in silico docking and microscale thermophoresis analysis,G protein-coupled bile acid receptor 1(GPBAR1)was identified as a potential membrane receptor that directly interacts with EGCG,mediating its regulatory effect on metabolism.Therefore,plant-derived products containing high levels of EGCG could be considered as natural feed additives for regulating glucose redistribution,as they can mitigate the elevated blood glucose levels in fish caused by consuming a HC diet.展开更多
Silver sulfide(Ag_(2)S)is one of the best photovoltaic materials in terms of elemental composition and both chemical stability and device stability.However,the lack of suitable film processing methods severely limits ...Silver sulfide(Ag_(2)S)is one of the best photovoltaic materials in terms of elemental composition and both chemical stability and device stability.However,the lack of suitable film processing methods severely limits the power conversion efficiency(PCE)improvement of Ag_(2)S-based devices.Here,we propose a specific solvent engineering train for high-quality Ag_(2)S absorber films by precisely tuning the dimethyl sulfoxide(DMSO)/N,Ndimethylformamide(DMF)constituent and post-deposition annealing temperature.A preferential transition in crystal orientation from(012)to(103)crystal planes is found to play a key role in photo-induced carrier behavior.The film surface morphology and grain size are fine-tuned,while the bulk defect concentration and mitigated interface carrier recombination are well suppressed.The optimized simple indium tin oxide(ITO)/Ag_(2)S/2,2’,7,7’-tetrakis(N,N-di-p-methoxyphenylamine)-9,9’-spirobifluorene(Spiro-OMeTAD)/Au device exhibits a significant increase in PCE from 0.77%to 2.57%,which is currently the highest value among the reported literatures of Ag_(2)S solar cells without an electron transport layer.展开更多
CDK4 is crucial for Gl-to-S transition of cell cycle. It is well established that ubiquitin-mediated degradations of CDK inhibitors and cycUns are pivotal for the timely and unidirectional progression of cell cycle. H...CDK4 is crucial for Gl-to-S transition of cell cycle. It is well established that ubiquitin-mediated degradations of CDK inhibitors and cycUns are pivotal for the timely and unidirectional progression of cell cycle. However, how CDK4 itself is modulated by ubiquitin-mediated degradation has been elusive. Here we report that the steady-state level of CDK4 is controlled by PAQR4, a member of the progestin and adipoQ receptor family, and SKP2, an E3 ubiquitin ligase. Knockdown of PAQR4 leads to reduction of cell proliferation, accompanied by reduced protein level of CDK4. PAQR4 reduces polyubiquitination and degradation of CDK4. PAQR4 interacts with the C-terminal lobe of CDK4. On the other hand, SKP2 also interacts with the C-terminal lobe of CDK4 and enhances polyubiquitination and degradation of CDK4. importantly, PAQR4 and SKP2 bind to the same region in CDK4, and PAQR4 competes with SKP2 for the binding, thereby abrogating SKP2-mediated ubiquitination of CDK4. Using a two-stage DMBA/TPA-induced skin cancer model, we find that PAQR4-deleted mice are resistant to chemical carcinogen-induced tumor formation. Collectively, our findings reveal that the steady-state level of CDK4 is controlled by the antagonistic actions between PAQR4 and SKP2, contributing to modulation of cell proliferation and tumorigenesis.展开更多
We aimed to evaluate the long-term effectiveness and safety of Burch colposuspension(BC) for stress urinary incontinence(SUI). In this prospective cohort study, 84 patients with SUI undergoing BC were enrolled from Fe...We aimed to evaluate the long-term effectiveness and safety of Burch colposuspension(BC) for stress urinary incontinence(SUI). In this prospective cohort study, 84 patients with SUI undergoing BC were enrolled from February 2004 to January 2010.Data on long-term subjective success and postoperative complications were collected at clinic visits and by telephone follow-up.During a mean follow-up period of 14.2 years, 68%(57/84) patients completed the follow-up. A total of 68.4% of patients(39/57) reported absence of SUI symptoms, 73.6%(42/57) were subjectively satisfied according to the Patient Global Impression of Improvement, and 68.4%(39/57) reported subjective success regarding urinary symptoms via the Urinary Distress Inventory Short Form. However, 28.1%(16/57) suffered at least one long-term postoperative complication and incident. Specifically, 1 in25(4.0%) sexually active patients reported dyspareunia, 3 patients(5.3%) had de novo overactive bladder, and 6 patients(10.5%)reported voiding dysfunction. Four patients(7.0%) reported new onset prolapse symptoms, and 3 patients(5.3%) underwent secondary urinary incontinence surgery. Our study indicated that Burch colposuspension is an effective procedure for SUI, and the cure effect was largely maintained for the 14-year follow-up period, with relatively low complication rates. BC should be considered a surgical option for SUI.展开更多
Although transvaginal mesh(TVM)repair is no longer used in some countries,long-term outcomes after TVM surgery are of great importance globally.However,reports with follow-up>10 years are limited.Thus,this study ai...Although transvaginal mesh(TVM)repair is no longer used in some countries,long-term outcomes after TVM surgery are of great importance globally.However,reports with follow-up>10 years are limited.Thus,this study aimed to report outcomes in a prospective cohort with at least 10 years of follow-up.Women with stageⅢ–Ⅳsymptomatic prolapse were approached consecutively from 2008 to 2013 at one tertiary hospital.The main outcome measure was symptomatic failure.Secondary outcomes included anatomic failure,recurrence,patient satisfaction,complications,and reoperation.The Kaplan-Meier curve was used to estimate the cumulative failure rate.Of the 121 patients enrolled in the study,103(85.1%)completed a median follow-up of 11 years.The estimated probability rates of symptomatic and anatomic failure were 17.6%and 8.8%in 11 years,respectively.The estimated incidence of symptomatic failure increased by 8.2%between 5 and 11 years;however,the corresponding rate for anatomic failure was 3.7%.The most common complication was vaginal mesh exposure,and its estimated probability increased from 19.3%to 28.4%from 5 to 11 years,respectively.Office trimming resolved 80.0%of vaginal exposures.These patients did not report decreased overall satisfaction.Patients with vaginal mesh exposure requiring>3 office procedures or mesh removal in the operating room(5.8%by 11 years)had lower satisfaction rates(P<0.01)and were defined as having severe mesh exposure.The rates of postoperative pain,reoperation,and Patient Global Impression of Improvement≥2 were 2.5%,3.3%,and 94.2%,respectively.The results of this study implied that TVM treatment gradually increased the symptomatic failure rate but provided durable anatomical support of the vaginal wall.Vaginal mesh exposure was common in women who were largely not sexually active;however,80%of the cases could be managed in the outpatient clinic,which did not affect patient satisfaction.展开更多
To the Editor:Pelvic organ prolapse(POP)is a common pelvic floor disorder in older women and is responsible for a significant decrease in health-related quality of life.With the increased longevity of women,POP is bec...To the Editor:Pelvic organ prolapse(POP)is a common pelvic floor disorder in older women and is responsible for a significant decrease in health-related quality of life.With the increased longevity of women,POP is becoming a major health concern.[1]Laparoscopic sacrocolpopexy(LSC)is a common mesh-based surgical approach for severe prolapse,and a high cure rate and few complications have been reported.[2]To our knowledge,the long-term durability,complications,and pelvic floor symptoms after LSC have not been fully evaluated in detail.A few studies assessed the 5-year outcome after LSC,but these reports were limited by their retrospective design,uneven follow-up time,or inconsistent outcome assessment.展开更多
Polycyclic aromatic hydrocarbons(PAHs)are major organic pollutants in soil.It is known that they are released to the atmosphere by wind via dust aerosol generation.However,it remains unclear how these pollutants are t...Polycyclic aromatic hydrocarbons(PAHs)are major organic pollutants in soil.It is known that they are released to the atmosphere by wind via dust aerosol generation.However,it remains unclear how these pollutants are transferred through the air/soil interface.In this study,dust aerosols were generated in the laboratory using soils(sandy loam and loam)with various physicochemical properties.The PAH concentrations of these soils and their generated dust aerosol were measured,showing that the enrichment factors(EFs)of PAHs were affected by soil texture,PAH contamination level,molecular weight of PAH species and aerosol sizes.The PAHs with higher EFs(6.24–123.35 in dust PM_(2.5);7.02–47.65 in dust PM_(10))usually had high molecular weights with more than four aromatic rings.In addition,the positive correlation between EFs of PAHs and the total OCaerosol content of dust aerosol in different particle sizes was also statistically significant(r=0.440,P<0.05).This work provides insights into the relationship between atmospheric PAHs and the contaminated soils and the transfer process of PAHs through the soil-air interface.展开更多
One major challenge of using DNA nanostructures for cellular and in vivo applications is their insufficiently structural integrity that stems from the non-covalent base pairing and stacking in complex cellular and phy...One major challenge of using DNA nanostructures for cellular and in vivo applications is their insufficiently structural integrity that stems from the non-covalent base pairing and stacking in complex cellular and physiological environment. The establishment of covalent bonds in DNA nanostructures can link individual strands more stably and therefore should improve the performance of DNA nanostructures in different scenarios where structural integrity is required. Here, we developed a convenient and effective method for constructing covalently stabilized DNA nanostructures by chemically inserting photo-crosslinker(^(CNV)K) in DNA sequences. These covalently linked DNA nanostructures were found to be more resistant to external interference, such as low cation concentrations and unspecific displacement on cell membranes. We also demonstrated that our strategy could improve the efficiency of cell surface receptor-mediated labeling and function regulations in living cells, which sheds light on broadening the biomedical applications of DNA nanostructures.展开更多
T lymphocytes are crucial for antiviral responses and provide a promising repertoire for potential therapies of viral diseases such as cytomegalovirus(CMV)infection1 and the ongoing COVID-19 pandemic caused by SARS-Co...T lymphocytes are crucial for antiviral responses and provide a promising repertoire for potential therapies of viral diseases such as cytomegalovirus(CMV)infection1 and the ongoing COVID-19 pandemic caused by SARS-CoV-2.^(2) CMV-related diseases occur once the host immune system is impaired or lacks a protective repertoire of virus-specific T lymphocytes.3 Adoptive transfer of T-cell receptor(TCR)-engineered T cells(TCR-Ts)provides an encouraging alternative treatment option for patients with CMV reactivation.^(4) However,generating TCR-Ts requires the identification of epitope-specific and functional TCR pairs.Modern single-cell sequencing techniques open up the ability to unravel TCR repertoires,^(5 )which offers a potential opportunity to screen functional TCR pairs for TCR-T therapy.Here,we report an efficient approach that combines ex vivo CD8+T-cell stimulation with single-cell RNA and TCR V(D)J sequencing to identify CMV-specific TCRs for generating TCR-Ts.展开更多
基金supported by the National Natural Science Foundation of China (Nos.42077193 and 21976034)the National Key R&D Program (Nos.2022YFC3702600 and 2022YFC3702601)the Shanghai Natural Science Foundation (23ZR1479700).
文摘Ultrasonic humidifiers are commonly used in households to maintain indoor humidity and generate a large number of droplets or spray aerosols.However,there have been various health concerns associated with humidifier use,largely due to aerosols generated during operation.Here,we investigated the size distribution,chemical composition,and charged fraction of aerosol particles emitted from commercial ultrasonic humidifiers.Heavy metals in water used for humidifiers were found to be highly enriched in the ultrasonic humidifier aerosols(UHA),with the enrichment factors ranging from 102 to 107.This enrichment may pose health concerns for the building occupants,as UHA concentrations of up to 106 particles/cm^(3) or 3 mg/m^(3) were observed.Furthermore,approximately 90%of UHA were observed to be electrically charged,for the first time according to our knowledge.Based on this discovery,we proposed and tested a newmethod to remove UHA by using a simple electrical field.The designed electrical field in this work can efficiently remove 81.4%of UHA.Therefore,applying this electrical field could be an effective method to significantly reduce the health risks by UHA.
基金support by the National Key Research and Development Program of China (Grant No. 2018YFC1313201)
文摘As immunotherapy has gained increasing interest as a new foundation for cancer therapy,some atypical response patterns,such as pseudoprogression and hyperprogression,have garnered the attention of physicians.Pseudoprogression is a phenomenon in which an initial increase in tumor size is observed or new lesions appear,followed by a decrease in tumor burden;this phenomenon can benefit patients receiving immunotherapy but often leads to premature discontinuation of treatment owing to the false judgment of progression.Accurately recognizing pseudoprogression is also a challenge for physicians.Because of the extensive attention on pseudoprogression,significant progress has been made.Some new criteria for immunotherapy,such as irRC,iRECIST and imRECIST,were proposed to accurately evaluate the response to immunotherapy.Many new detection indexes,such as ctDNA and IL-8,have also been used to identify pseudoprogression.In this review,the definition,evaluation criteria,mechanism,monitoring,management and prognosis of pseudoprogression are summarized,and diagnostic and treatment processes for patients with progression but with a suspicion of pseudoprogression are proposed;these processes could be helpful for physicians in clinical practice and enhances the understanding of pseudoprogression.
基金supported by National Natural Science Foundation of China(Grant No.11804005,11375136,12204014)Anyang Institute of Technology Research Cultivation Fund(Grant No.YPY2019002)。
文摘Photocatalytic reduction of CO_(2) is considered as a kind of promising technologies for solving the greenhouse effect.Herein,a novel hybrid structure of g-C_(3)N_(4)/ZnO/Ti_(3)C_(2) photocatalysts was designed and fabricated to investigate their abilities for CO_(2) reduction.As demonstration,heterojunction of g-C_(3)N_(4)/ZnO can improve photogenerated carriers’separation,the addition of Ti_(3)C_(2) fragments can further facilitate the photocatalytic performance from CO_(2) to CO.Hence,g-C_(3)N_(4)/ZnO/Ti_(3)C_(2) has efficiently increased CO production by 8 and 12 times than pristine g-C_(3)N_(4) and ZnO,respectively.Which is ascribed to the photogenerated charge migration promoted by metallic Ti_(3)C_(2).This work provides a guideline for designing efficient hybrid catalysts on other applications in the renewable energy fields.
基金supported by the National Natural Science Foundation of China(No.32070182)the Key Project of Jiangsu Commission of Health(No.ZD2021049)+3 种基金the Highlevel Talent Program at Affiliated Kunshan Hospital of Jiangsu University(No.gccrc2022002)the Suzhou Municipal Science and Technology Development Plan(No.SKYD2023002)the Suzhou Municipal Key Discipline Construction Project(No.SZXK202124)the Talent Research Project of Suzhou Health Talent Plan(No.GSWS2023005),China.
文摘Extracellular vesicles(EVs)are nano-sized bilayer vesicles that are shed or secreted by virtually every cell type.A variety of biomolecules,including proteins,lipids,coding and non-coding RNAs,and mitochondrial DNA,can be selectively encapsulated into EVs and delivered to nearby and distant recipient cells,leading to alterations in the recipient cells,suggesting that EVs play an important role in intercellular communication.EVs play effective roles in physiology and pathology and could be used as diagnostic and therapeutic tools.At present,although the mechanisms of exosome biogenesis and secretion in donor cells are well understood,the molecular mechanism of EV recognition and uptake by recipient cells is still unclear.This review summarizes the current understanding of the molecular mechanisms of EVs’biological journey in recipient cells,from recognition to uptake and cargo release.Furthermore,we highlight how EVs escape endolysosomal degradation after uptake and thus release cargo,which is crucial for studies applying EVs as drug-targeted delivery vehicles.Knowledge of the cellular processes that govern EV uptake is important to shed light on the functions of EVs as well as on related clinical applications.
基金supported by the National Natural Science Foundation of China(No.81070671)the National Basic Research Program(973 ProgramNo.2009CB918904)
文摘Dietary meats play a crucial role in human health. The objective of this survey was to determine the fatty acid content and omega-6/omega-3 polyunsaturated fatty acids （n-6/n-3 PUFA） ratio of fresh red meat （beef and pork） from four cities （Shanghai, Nanjing, Yinchuan and Hohhot） in China. The results showed that the n-6/n-3 PUFA ratio from all the samples ranged from 6 to 23. The total n-6 PUFA concentrations ranged from 290.54 mg/100 g in beef from Nanjing to 1601.48 mg/100 g in pork from Hohhot, whereas the total concentrations of n-3 PUFA ranged from 46.34 mg/100 g in beef from Nanjing to 96.03 mg/100 g in pork from Nanjing. The results indicated that the n-6/n-3 ratio in the red meat from all four regions is unbalanced and is much higher than that （〈 5：1） rec- ommended by the WHO/FAO. The total amount of n-3 PUFA was far lower than the required daily dose. There- fore, potential solutions to increase the n-3 PUFA content in meat products or to provide alternative source of n-3 PUFA should be explored.
基金supported by the National Natural Science Foundation of China (Nos. 81573269, 21572015, 21877007, 91753202 and 21702007)and the open funding of the State Key Laboratory of Phytochemistry and Plant Resources in West China
文摘Oleanolic acid(OA) and echinocystic acid(EA), two naturally occurring pentacyclic oleanane triterpenes,are gaining increasing attention due to their promising pharmacological activities. Conjugation with amphiphilic α(β)-cyclodextrin(CD) via "click chemistry" can improve their solubility and anti-HCV entry potency. In the present work,four water-soluble β-CD-pentacyclic triterpene conjugates were designed and synthesized, in which OA and EA was coupled to one of the primary hydroxyl groups of β-CD via ester and amide bonds. The structures of the conjugates were unambiguously determined by ~1H NMR, ^(13)C NMR and HRMS or MALDI-TOF-MS. All the conjugates showed lower hydrophobicity(AlogP) than their parent compounds and no significant cytotoxicity was found to HL-60, A549, Hela and Bel-7402 cells at concentrations up to 10 μmol/L. Further anti-HCV entry activity and mechanism studies are under way in our laboratory.
基金Supported by the Jiangsu Provincial Social Development Program of the Key R&D Project(BE2022803)Natural Science Foundation of Jiangsu(BK20201485)+1 种基金Jiangsu Provincial Key Medical Discipline(ZDXK202249)Scientific Research Project of Jiangsu Health Commission(M2022085).
文摘Objective:In this study,we aimed to identify novel genetic loci and protein biomarkers associated with silicosis susceptibility in Chinese workers through integrated proteomic and genomic analyses and to develop an early diagnostic prediction model.Methods:A genome-wide association study(GWAS)was conducted on 163 patients with silicosis and 183 controls,followed by Olink proteomic profiling of 92 plasma proteins.Protein quantitative trait loci(pQTL)mapping,Mendelian randomization(MR),and Bayesian co-localization were used to infer causal relationships.A causal protein risk score(CPRS)model integrating genetic and proteomic data was developed and validated using 10-fold cross-validation.Results:GWAS identified 16 novel risk loci(P<1×10^(-5)),including rs6677666(WLS)and rs2272528(COL4A4).MR analysis revealed eight plasma proteins associated with silicosis risk,with MMP12,EGF,Gal_9,GZMA,and ICOSLG showing significant differential expression(P<0.05).The CPRS model combining these proteins demonstrated a high diagnostic accuracy(AUC=0.915),outperforming traditional clinical variables.Conclusion:This multi-omics study uncovered genetic and proteomic markers linked to silicosis susceptibility and established a robust predictive model.The integration of GWAS and proteomics offers novel insights into the pathogenesis of silicosis,and supports development of early detection and prevention policies for high-risk populations.
基金supported by the National Key R&D Program of China(grant nos.2021YFC2701403)the National Natural Science Foundation of China(grant nos.82271656,82171620 and 82360297)+2 种基金the National High Level Hospital Clinical Research Funding(grant nos.2022-PUMCH-A-205)Science and Technology Program of Guizhou Province,China(grant nos:Qian Ke He Ji Chu-ZK[2023]Yi Ban 204)Special Foundation for Taishan Scholars Program of Shandong Province(grant nos.tsqnz20240855)。
文摘Congenital deficiency or extensive cervical injury leads to female genital tract obstruction and cervical laxity,resulting in infertility or miscarriage.Current clinical approaches could be conducted to restore the continuity of cervix.However,full-thickness and large-scale cervical regeneration with complete structural and functional restoration have not been reported.In this study,we fabricated a double-layered collagen membrane(CM)scaffold based on decellularized extracellular matrix.Each layer was adapted to support the growth of epithelial cells and stromal cells,respectively.Further,the thickness and folded“sandwich”structure were tailored to match the cervical structure.When transplanted into rabbit full-thickness and total ectocervix excision models,only CM scaffold groups enabled the regeneration of neo-ectocervix tissue,including epithelium,stroma and muscular layers after 3 and 6 months.The neo-ectocervix regenerated by CM scaffolds exhibited significantly higher expression of secretory glands and estrogen receptors,more secretion of neutral and acidic mucins,showing functional maturity of regenerated epithelium.Notably,CM scaffolds supported the regeneration of stroma and muscular layers.The mechanical strength of neo ectocervix was comparable to that of normal ectocervix.CM scaffolds demonstrate good biocompatibility,support different cell growth,and enhance superior regeneration of epithelium,stromal and muscular tissue,confirming its construction capacity as new strategies for addressing cervical deficiency and damage.
基金supported by National Key R&D Program of China(2023YFD1702102)Anhui Provincial Natural Science Foundation(2308085Y26)+1 种基金Research Funds of Joint Research Center for Food Nutrition and Health of IHM(2023SJY01)Natural Science Research Project of Anhui Educational Committee(2023AH051026).
文摘Exploring exogenous additives to enhance non-protein energy ingredient utilization in fish is highly anticipated.Epigallocatechin-3-gallate(EGCG)is a prominent polyphenol found in green tea.To assess the regulatory effect of EGCG on metabolic disorders induced by an excess of non-protein energy sources in grass carp(Ctenopharyngodon idella),five isonitrogenous diets were formulated:a control diet(23% digestible carbohydrates,4.7% crude lipids),a high-carbohydrate(HC;48% digestible carbohydrates,4.7% crude lipids)diet,a high-fat(HF;23% digestible carbohydrates,9.6% crude lipid)diet,the HC diet supplemented with 0.05% EGCG(HC+EGCG)and the HF diet supplemented with 0.05% EGCG(HF+EGCG).The diets were fed to 450 fish(initial body weight=8.50 g)in three replicates for eight weeks.After the feeding trial,compared with the control group,EGCG significantly alleviated the growth suppression induced by HC or HF intake(P<0.05).Dietary EGCG supplementation downregulated the expression of fatty acid synthesis genes(srebp1,acc,and fas)(P<0.05).Further,EGCG supplementation to the HC diet significantly increased hepatic glycogen synthesis and suppressed elevated glucose concentration through gluconeogenesis(P<0.05).Additionally,EGCG supplementation significantly reduced excess circulating glucose by inhibiting α-amylase activities and decreasing the expression of glucose transporter 2(glut2)in the intestines of grass carp(P<0.05).Furthermore,in order to reveal the mechanism of EGCG affecting feeding and metabolism,transcriptome analysis on grass carp hepatocytes was conducted.The results showed that the leptin b(lepb)and G protein-coupled bile acid receptor 1(gpbar1)were key candidate genes among differentially expressed genes from the cell transcriptome.Further in vivo studies found that the high leptin release induced by EGCG may play a pivotal role in the regulation of feed intake and appetite.Moreover,through in silico docking and microscale thermophoresis analysis,G protein-coupled bile acid receptor 1(GPBAR1)was identified as a potential membrane receptor that directly interacts with EGCG,mediating its regulatory effect on metabolism.Therefore,plant-derived products containing high levels of EGCG could be considered as natural feed additives for regulating glucose redistribution,as they can mitigate the elevated blood glucose levels in fish caused by consuming a HC diet.
基金financially supported by the National Natural Science Foundation of China(Nos.52472255,52072327,and 22309158)Key Research and Development Project of Henan Province(No.231111232100)+4 种基金Zhongyuan Thousand Talents(Zhongyuan Scholars)Program of Henan Province(No.202101510004)Natural Science Foundation of Henan Province(Nos.242300421715 and 232300420099)Academic Degrees&Graduate Education Reform Project of Henan Province(No.2021SJGLX060Y)Key Scientific Research Projects of Henan Province Higher Education Institutions(Nos.24A150040,23B430009,24B430017,and 24A530008)Technology Research and Development Program of Henan province(No.242102310466).
文摘Silver sulfide(Ag_(2)S)is one of the best photovoltaic materials in terms of elemental composition and both chemical stability and device stability.However,the lack of suitable film processing methods severely limits the power conversion efficiency(PCE)improvement of Ag_(2)S-based devices.Here,we propose a specific solvent engineering train for high-quality Ag_(2)S absorber films by precisely tuning the dimethyl sulfoxide(DMSO)/N,Ndimethylformamide(DMF)constituent and post-deposition annealing temperature.A preferential transition in crystal orientation from(012)to(103)crystal planes is found to play a key role in photo-induced carrier behavior.The film surface morphology and grain size are fine-tuned,while the bulk defect concentration and mitigated interface carrier recombination are well suppressed.The optimized simple indium tin oxide(ITO)/Ag_(2)S/2,2’,7,7’-tetrakis(N,N-di-p-methoxyphenylamine)-9,9’-spirobifluorene(Spiro-OMeTAD)/Au device exhibits a significant increase in PCE from 0.77%to 2.57%,which is currently the highest value among the reported literatures of Ag_(2)S solar cells without an electron transport layer.
基金supported by the National Natural Science Foundation of China(82171620 and 81830043)the National Key R&D Program of China(2021YFC2701403 and 2018YFC2002201)the National High Level Hospital Clinical Research Funding(2022-PUMCH-A-205 and 2022-PUMCH-A-114)。
文摘CDK4 is crucial for Gl-to-S transition of cell cycle. It is well established that ubiquitin-mediated degradations of CDK inhibitors and cycUns are pivotal for the timely and unidirectional progression of cell cycle. However, how CDK4 itself is modulated by ubiquitin-mediated degradation has been elusive. Here we report that the steady-state level of CDK4 is controlled by PAQR4, a member of the progestin and adipoQ receptor family, and SKP2, an E3 ubiquitin ligase. Knockdown of PAQR4 leads to reduction of cell proliferation, accompanied by reduced protein level of CDK4. PAQR4 reduces polyubiquitination and degradation of CDK4. PAQR4 interacts with the C-terminal lobe of CDK4. On the other hand, SKP2 also interacts with the C-terminal lobe of CDK4 and enhances polyubiquitination and degradation of CDK4. importantly, PAQR4 and SKP2 bind to the same region in CDK4, and PAQR4 competes with SKP2 for the binding, thereby abrogating SKP2-mediated ubiquitination of CDK4. Using a two-stage DMBA/TPA-induced skin cancer model, we find that PAQR4-deleted mice are resistant to chemical carcinogen-induced tumor formation. Collectively, our findings reveal that the steady-state level of CDK4 is controlled by the antagonistic actions between PAQR4 and SKP2, contributing to modulation of cell proliferation and tumorigenesis.
基金supported by the National Natural Science Foundation of China (81830043 and 81771561)the National Key Research and Development Program of China (2018YFC2002201)。
文摘We aimed to evaluate the long-term effectiveness and safety of Burch colposuspension(BC) for stress urinary incontinence(SUI). In this prospective cohort study, 84 patients with SUI undergoing BC were enrolled from February 2004 to January 2010.Data on long-term subjective success and postoperative complications were collected at clinic visits and by telephone follow-up.During a mean follow-up period of 14.2 years, 68%(57/84) patients completed the follow-up. A total of 68.4% of patients(39/57) reported absence of SUI symptoms, 73.6%(42/57) were subjectively satisfied according to the Patient Global Impression of Improvement, and 68.4%(39/57) reported subjective success regarding urinary symptoms via the Urinary Distress Inventory Short Form. However, 28.1%(16/57) suffered at least one long-term postoperative complication and incident. Specifically, 1 in25(4.0%) sexually active patients reported dyspareunia, 3 patients(5.3%) had de novo overactive bladder, and 6 patients(10.5%)reported voiding dysfunction. Four patients(7.0%) reported new onset prolapse symptoms, and 3 patients(5.3%) underwent secondary urinary incontinence surgery. Our study indicated that Burch colposuspension is an effective procedure for SUI, and the cure effect was largely maintained for the 14-year follow-up period, with relatively low complication rates. BC should be considered a surgical option for SUI.
基金supported by the National Natural Science Foundation of China(81830043,81771561)the National High Level Hospital Clinical Research Funding(2022-PUMCH-A-113,2022-PUMCH-C-031)+1 种基金the National Key Research and Development Program of China(2018YFC2002201)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2020-PT320-003)。
文摘Although transvaginal mesh(TVM)repair is no longer used in some countries,long-term outcomes after TVM surgery are of great importance globally.However,reports with follow-up>10 years are limited.Thus,this study aimed to report outcomes in a prospective cohort with at least 10 years of follow-up.Women with stageⅢ–Ⅳsymptomatic prolapse were approached consecutively from 2008 to 2013 at one tertiary hospital.The main outcome measure was symptomatic failure.Secondary outcomes included anatomic failure,recurrence,patient satisfaction,complications,and reoperation.The Kaplan-Meier curve was used to estimate the cumulative failure rate.Of the 121 patients enrolled in the study,103(85.1%)completed a median follow-up of 11 years.The estimated probability rates of symptomatic and anatomic failure were 17.6%and 8.8%in 11 years,respectively.The estimated incidence of symptomatic failure increased by 8.2%between 5 and 11 years;however,the corresponding rate for anatomic failure was 3.7%.The most common complication was vaginal mesh exposure,and its estimated probability increased from 19.3%to 28.4%from 5 to 11 years,respectively.Office trimming resolved 80.0%of vaginal exposures.These patients did not report decreased overall satisfaction.Patients with vaginal mesh exposure requiring>3 office procedures or mesh removal in the operating room(5.8%by 11 years)had lower satisfaction rates(P<0.01)and were defined as having severe mesh exposure.The rates of postoperative pain,reoperation,and Patient Global Impression of Improvement≥2 were 2.5%,3.3%,and 94.2%,respectively.The results of this study implied that TVM treatment gradually increased the symptomatic failure rate but provided durable anatomical support of the vaginal wall.Vaginal mesh exposure was common in women who were largely not sexually active;however,80%of the cases could be managed in the outpatient clinic,which did not affect patient satisfaction.
基金supported by grants from the National Natural Science Foundation of China(No.81830043)the Fundamental Research Funds for the Central Universities(No.3332022118)+1 种基金the National Key R&D Program of China(Nos.2021YFC2701300 and 2021YFC2701302)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(No.2021-PT320-001)
文摘To the Editor:Pelvic organ prolapse(POP)is a common pelvic floor disorder in older women and is responsible for a significant decrease in health-related quality of life.With the increased longevity of women,POP is becoming a major health concern.[1]Laparoscopic sacrocolpopexy(LSC)is a common mesh-based surgical approach for severe prolapse,and a high cure rate and few complications have been reported.[2]To our knowledge,the long-term durability,complications,and pelvic floor symptoms after LSC have not been fully evaluated in detail.A few studies assessed the 5-year outcome after LSC,but these reports were limited by their retrospective design,uneven follow-up time,or inconsistent outcome assessment.
基金supported by the National Natural Science Foundation of China(Nos.42077193,21906024,and 92044301)the Shanghai Natural Science Foundation(China)(No.19ZR1404000)。
文摘Polycyclic aromatic hydrocarbons(PAHs)are major organic pollutants in soil.It is known that they are released to the atmosphere by wind via dust aerosol generation.However,it remains unclear how these pollutants are transferred through the air/soil interface.In this study,dust aerosols were generated in the laboratory using soils(sandy loam and loam)with various physicochemical properties.The PAH concentrations of these soils and their generated dust aerosol were measured,showing that the enrichment factors(EFs)of PAHs were affected by soil texture,PAH contamination level,molecular weight of PAH species and aerosol sizes.The PAHs with higher EFs(6.24–123.35 in dust PM_(2.5);7.02–47.65 in dust PM_(10))usually had high molecular weights with more than four aromatic rings.In addition,the positive correlation between EFs of PAHs and the total OCaerosol content of dust aerosol in different particle sizes was also statistically significant(r=0.440,P<0.05).This work provides insights into the relationship between atmospheric PAHs and the contaminated soils and the transfer process of PAHs through the soil-air interface.
基金supported by the National Key Research and Development Program of China (2021YFA0909400)the National Natural Science Foundation of China (21974087, 81974315)+6 种基金Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (20181709)Shanghai Rising-Star Program (20QA1405800)the General Projects of China Postdoctoral Fund (2021M692104)Innovative Research Team of High-Level Local Universities in Shanghaifaculty start-up funding support from the Institute of Molecular Medicine of Shanghai Jiao Tong UniversityRecruitment Program of Global Youth Experts of China。
文摘One major challenge of using DNA nanostructures for cellular and in vivo applications is their insufficiently structural integrity that stems from the non-covalent base pairing and stacking in complex cellular and physiological environment. The establishment of covalent bonds in DNA nanostructures can link individual strands more stably and therefore should improve the performance of DNA nanostructures in different scenarios where structural integrity is required. Here, we developed a convenient and effective method for constructing covalently stabilized DNA nanostructures by chemically inserting photo-crosslinker(^(CNV)K) in DNA sequences. These covalently linked DNA nanostructures were found to be more resistant to external interference, such as low cation concentrations and unspecific displacement on cell membranes. We also demonstrated that our strategy could improve the efficiency of cell surface receptor-mediated labeling and function regulations in living cells, which sheds light on broadening the biomedical applications of DNA nanostructures.
基金supported by the Science,Technology and Innovation Commission of Shenzhen Municipality under grant No.JCYJ20170303151334808 and grant No.JSGG20180508152912700The first author would like to acknowledge financial support from the China Scholarship Council(CSC)(grant No.201904910476).
文摘T lymphocytes are crucial for antiviral responses and provide a promising repertoire for potential therapies of viral diseases such as cytomegalovirus(CMV)infection1 and the ongoing COVID-19 pandemic caused by SARS-CoV-2.^(2) CMV-related diseases occur once the host immune system is impaired or lacks a protective repertoire of virus-specific T lymphocytes.3 Adoptive transfer of T-cell receptor(TCR)-engineered T cells(TCR-Ts)provides an encouraging alternative treatment option for patients with CMV reactivation.^(4) However,generating TCR-Ts requires the identification of epitope-specific and functional TCR pairs.Modern single-cell sequencing techniques open up the ability to unravel TCR repertoires,^(5 )which offers a potential opportunity to screen functional TCR pairs for TCR-T therapy.Here,we report an efficient approach that combines ex vivo CD8+T-cell stimulation with single-cell RNA and TCR V(D)J sequencing to identify CMV-specific TCRs for generating TCR-Ts.
