Non-alcoholic fatty liver disease(NAFLD)is a liver condition that is widely prevalent across the world.A considerable number of people with NAFLD have the potential to progress to a more severe form of the condition k...Non-alcoholic fatty liver disease(NAFLD)is a liver condition that is widely prevalent across the world.A considerable number of people with NAFLD have the potential to progress to a more severe form of the condition known as nonalcoholic steatohepatitis(NASH),accompanied by bridging fibrosis.This advancement is more likely if the patient has metabolic risk factors such as obesity or type 2 diabetes that deteriorate over time.Additionally,even slight inflammation or fibrosis in NAFLD can significantly increase the likelihood of progression compared to steatosis alone.This underscores the importance of revising the present methods of monitoring NAFLD patients to ensure early detection and effective management of the disease.展开更多
Flexible strain sensors have received tremendous attention because of their potential applications as wearable sensing devices.However, the integration of key functions into a single sensor, such as high stretchabilit...Flexible strain sensors have received tremendous attention because of their potential applications as wearable sensing devices.However, the integration of key functions into a single sensor, such as high stretchability, low hysteresis, self-adhesion, andexcellent antifreezing performance, remains an unmet challenge. In this respect, zwitterionic hydrogels have emerged asideal material candidates for breaking through the above dilemma. The mechanical properties of most reported zwitterionichydrogels, however, are relatively poor, significantly restricting their use under load-bearing conditions. Traditional improve-ment approaches often involve complex preparation processes, making large-scale production challenging. Additionally,zwitterionic hydrogels prepared with chemical crosslinkers are typically fragile and prone to irreversible deformation underlarge strains, resulting in the slow recovery of structure and function. To fundamentally enhance the mechanical properties ofpure zwitterionic hydrogels, the most effective approach is the regulation of the chemical structure of zwitterionic monomersthrough a targeted design strategy. This study employed a novel zwitterionic monomer carboxybetaine urethane acrylate(CBUTA), which contained one urethane group and one carboxybetaine group on its side chain. Through the direct polym-erization of ultrahigh concentration monomer solutions without adding any chemical crosslinker, we successfully developedpure zwitterionic supramolecular hydrogels with significantly enhanced mechanical properties, self-adhesive behavior, andantifreezing performance. Most importantly, the resultant zwitterionic hydrogels exhibited high tensile strength and tough-ness and displayed ultralow hysteresis under strain conditions up to 1100%. This outstanding performance was attributedto the unique liquid–liquid phase separation phenomenon induced by the ultrahigh concentration of CBUTA monomers inan aqueous solution, as well as the enhanced polymer chain entanglement and the strong hydrogen bonds between urethanegroups on the side chains. The potential application of hydrogels in strain sensors and high-performance triboelectric nano-generators was further explored. Overall, this work provides a promising strategy for developing pure zwitterionic hydrogelsfor flexible strain sensors and self-powered electronic devices.展开更多
Lingguizhugan Decoction(LGZG)has been investigated in basic studies,with satisfactory effects on insulin resistance in non-alcoholic fatty liver disease(NAFLD).This translational approach aimed to explore the effect a...Lingguizhugan Decoction(LGZG)has been investigated in basic studies,with satisfactory effects on insulin resistance in non-alcoholic fatty liver disease(NAFLD).This translational approach aimed to explore the effect and underlying mechanism of LGZG in clinical setting.A randomized,double-blinded,placebo-controlled trial was performed.A total of 243 eligible participants with NAFLD were equally allocated to receive LGZG(two groups:standard dose and low dose)or placebo for 12 weeks on the basis of lifestyle modifications.The primary efficacy variable was homeostasis model assessment of insulin resistance(HOMA-IR).Analyses were performed in two populations in accordance with body mass index(BMI;overweight/obese,BMI 24 kg/m^(2);lean,BMI<24 kg/m^(2)).For overweight/obese participants,low-dose LGZG significantly decreased their HOMA-IR level compared with placebo(0.19(1.47)versus 0.08(1.99),P=0.038).For lean subjects,neither dose of LGZG showed a superior effect compared with placebo.Methylated DNA immunoprecipitation sequencing and real-time qPCR found that the DNA N6-methyladenine modification levels of protein phosphatase 1 regulatory subunit 3A(PPP1R3A)and autophagy related 3(ATG3)significantly increased after LGZG intervention in overweight/obese population.Low-dose LGZG effectively improved insulin resistance in overweight/obese subjects with NAFLD.The underlying mechanism may be related to the regulation of DNA N6-methyladenine modification of PPP1R3A and ATG3.Lean subjects may not be a targeted population for LGZG.展开更多
Ebola virus （EBOV） is a key member of Filoviridae family and causes severe human infectious diseases with high morbidity and mortality. As a typical negative-sense single-stranded RNA （-ssRNA） viruses, EBOV posses...Ebola virus （EBOV） is a key member of Filoviridae family and causes severe human infectious diseases with high morbidity and mortality. As a typical negative-sense single-stranded RNA （-ssRNA） viruses, EBOV possess a nucleocapsid protein （NP） to facilitate genomic RNA encapsidation to form viral ribonucleoprotein complex （RNP） together with genome RNA and polymerase, which plays the most essential role in virus proliferation cycle. However, the mechanism of EBOV RNP formation remains unclear. In this work, we solved the high resolution structure of core domain of EBOV NP. The polypeptide of EBOV NP core domain （NPcore） pos- sesses an N-lobe and C-lobe to clamp a RNA binding groove, presenting similarities with the structures of the other reported viral NPs encoded by the members from Mononegavirales order. Most strikingly, a hydrophobic pocket at the surface of the C-lobe is occupied by an a- helix of EBOV NPcore itself, which is highly conserved among filoviridae family. Combined with other bio- chemical and biophysical evidences, our results provides great potential for understanding the mechanism underlying EBOV RNP formation via the mobility of EBOV NP element and enables the development of antiviral therapies targeting EBOV RNP formation.展开更多
Triboelectric nanogenerator(TENG)can realize a variety of mechanical energy collections in the environment,which has great potential in the field of wearable energy.However,many TENGs could rarely be satisfactory to w...Triboelectric nanogenerator(TENG)can realize a variety of mechanical energy collections in the environment,which has great potential in the field of wearable energy.However,many TENGs could rarely be satisfactory to wearable electronics promotion because of their expensive raw materials and complex manufacturing processes.In this study,a type of porous structure carbon powder/manganese dioxide(C/MnO_(2))nanocomposite is introduced.The material adopts low-cost,high-yield carbon powder,can be prepared in one step through a simple,economical,and environmentally friendly hydrothermal preparation process,and has high economic practicality.Superior power generation performance was obtained by modulating the charge trapping ability and storage capacity of polydimethylsiloxane@C/MnO_(2)(PDMS@C/MnO_(2))film based on variations in the weight-loading of C/MnO_(2).The maximum output voltage of carbon powder/manganese dioxide TENG(CM-TENG)is 63 V,which is 2.1 times that of PDMS-TENG and 1.86 times that of carbon powder TENG(C-TENG)and can easily light up 53 LEDs.Furthermore,CM-TENG can convert biological motion energy into electrical signals to detect human hand movements.The CM-TENG self-powered system can successfully drive various microelectronic devices,such as electronic watches,liquid crystal displays(LCDs),and calculators.This study provides a reliable,low-cost,high-performance,and widely applicable electronic system that shows great potential in future fields such as wearable devices and micro-sensing systems.展开更多
Objective: This study aimed to investigate the association between single-nucleotide polymorphisms (SNPs) ofPCSK1 (proprotein convertase subtilisin/kexin type 1) related to obesity and nonalcoholic fatty liver disease...Objective: This study aimed to investigate the association between single-nucleotide polymorphisms (SNPs) ofPCSK1 (proprotein convertase subtilisin/kexin type 1) related to obesity and nonalcoholic fatty liver disease (NAFLD).Methods: In this case-control observational study, four candidate SNPs (rs6234, rs155971, rs6232, rs3811951) ofPCSK1 were genotyped in 732 NAFLD patients and 823 healthy control participants, all of whom were of ethnic Han Chinese descent. All participants came from Shanghai, China, and joined our study during 2015 to 2016. The frequencies of each allele and genotype, paired linkage disequilibrium, and haplotype were calculated on the SHEsis platform. In addition to SHEsis, five different genetic models (codominant, dominant, recessive, overdominant, and log-additive) were employed to identify the correlation between genotype frequency and NAFLD. This study was approved by the Medical Ethics Committee of Shanghai University of Traditional Chinese Medicine (approved No. 2017LCSY069).Results: In a comparison of NAFLD patients and healthy participants, none of the fourPCSK1 SNPs were significantly correlated with the occurrence of NAFLD (P>0.05), in either genotypic or allelic distribution. The recessive model of rs3811951 appeared to show a correlation (odds ratio=1.077;95% confidence interval=0.924-1.256;P=0.04), but there was no statistical significance after Bonferroni correction (Pcorr>0.0125).Conclusions: Four obesity-relatedPCSK1 SNPs (rs6234, rs155971, rs6232, rs3811951) showed no significant correlation with the development of NAFLD in a Han Chinese population.展开更多
基金supported by a Three-year action plan for Shanghai(ZY(2021-2023)-0211)National Natural Science Foundation of China(No.81973730)+4 种基金Local Colleges Faculty Constitution of Shanghai MSTC 2022(No.22010504300)Shanghai Collaborative Innovation Center for Chronic Disease Prevention and Health Services(2021 Science and Technology 02-37)China Postdoctoral Science Foundation,No.72 General Fund,2022(No.2022M722164)Shanghai 2023"Science and Technology Innovation Action Plan"Qi Ming Xing Cultivation(Yang Fan Project,No.23YF1447700)Shanghai Health Commission for Traditional Chinese Medicine Research(No.2022QN014).
文摘Non-alcoholic fatty liver disease(NAFLD)is a liver condition that is widely prevalent across the world.A considerable number of people with NAFLD have the potential to progress to a more severe form of the condition known as nonalcoholic steatohepatitis(NASH),accompanied by bridging fibrosis.This advancement is more likely if the patient has metabolic risk factors such as obesity or type 2 diabetes that deteriorate over time.Additionally,even slight inflammation or fibrosis in NAFLD can significantly increase the likelihood of progression compared to steatosis alone.This underscores the importance of revising the present methods of monitoring NAFLD patients to ensure early detection and effective management of the disease.
基金supported by the National Natural Science Foundation of China(Nos.T2222013 and 52073203)Tianjin Natural Science Foundation(No.22JCQNJC01040)the State Key Laboratory of Molecular Engineering of Polymers(Hehai University)(No.K2024-19).
文摘Flexible strain sensors have received tremendous attention because of their potential applications as wearable sensing devices.However, the integration of key functions into a single sensor, such as high stretchability, low hysteresis, self-adhesion, andexcellent antifreezing performance, remains an unmet challenge. In this respect, zwitterionic hydrogels have emerged asideal material candidates for breaking through the above dilemma. The mechanical properties of most reported zwitterionichydrogels, however, are relatively poor, significantly restricting their use under load-bearing conditions. Traditional improve-ment approaches often involve complex preparation processes, making large-scale production challenging. Additionally,zwitterionic hydrogels prepared with chemical crosslinkers are typically fragile and prone to irreversible deformation underlarge strains, resulting in the slow recovery of structure and function. To fundamentally enhance the mechanical properties ofpure zwitterionic hydrogels, the most effective approach is the regulation of the chemical structure of zwitterionic monomersthrough a targeted design strategy. This study employed a novel zwitterionic monomer carboxybetaine urethane acrylate(CBUTA), which contained one urethane group and one carboxybetaine group on its side chain. Through the direct polym-erization of ultrahigh concentration monomer solutions without adding any chemical crosslinker, we successfully developedpure zwitterionic supramolecular hydrogels with significantly enhanced mechanical properties, self-adhesive behavior, andantifreezing performance. Most importantly, the resultant zwitterionic hydrogels exhibited high tensile strength and tough-ness and displayed ultralow hysteresis under strain conditions up to 1100%. This outstanding performance was attributedto the unique liquid–liquid phase separation phenomenon induced by the ultrahigh concentration of CBUTA monomers inan aqueous solution, as well as the enhanced polymer chain entanglement and the strong hydrogen bonds between urethanegroups on the side chains. The potential application of hydrogels in strain sensors and high-performance triboelectric nano-generators was further explored. Overall, this work provides a promising strategy for developing pure zwitterionic hydrogelsfor flexible strain sensors and self-powered electronic devices.
基金This study is supported by the National Natural Science Foundation of China(No.816220108030)the Evidence-based Capacity Building Project for Basic Traditional Chinese Medicine-Specialized Diseases(No.2019XZZX-XH012)Shanghai Three-year Action Planfor Accelerating the Development of Traditional Chinese Medicine(ZY(2018-2020)-CCCX-2002-01).
文摘Lingguizhugan Decoction(LGZG)has been investigated in basic studies,with satisfactory effects on insulin resistance in non-alcoholic fatty liver disease(NAFLD).This translational approach aimed to explore the effect and underlying mechanism of LGZG in clinical setting.A randomized,double-blinded,placebo-controlled trial was performed.A total of 243 eligible participants with NAFLD were equally allocated to receive LGZG(two groups:standard dose and low dose)or placebo for 12 weeks on the basis of lifestyle modifications.The primary efficacy variable was homeostasis model assessment of insulin resistance(HOMA-IR).Analyses were performed in two populations in accordance with body mass index(BMI;overweight/obese,BMI 24 kg/m^(2);lean,BMI<24 kg/m^(2)).For overweight/obese participants,low-dose LGZG significantly decreased their HOMA-IR level compared with placebo(0.19(1.47)versus 0.08(1.99),P=0.038).For lean subjects,neither dose of LGZG showed a superior effect compared with placebo.Methylated DNA immunoprecipitation sequencing and real-time qPCR found that the DNA N6-methyladenine modification levels of protein phosphatase 1 regulatory subunit 3A(PPP1R3A)and autophagy related 3(ATG3)significantly increased after LGZG intervention in overweight/obese population.Low-dose LGZG effectively improved insulin resistance in overweight/obese subjects with NAFLD.The underlying mechanism may be related to the regulation of DNA N6-methyladenine modification of PPP1R3A and ATG3.Lean subjects may not be a targeted population for LGZG.
文摘Ebola virus （EBOV） is a key member of Filoviridae family and causes severe human infectious diseases with high morbidity and mortality. As a typical negative-sense single-stranded RNA （-ssRNA） viruses, EBOV possess a nucleocapsid protein （NP） to facilitate genomic RNA encapsidation to form viral ribonucleoprotein complex （RNP） together with genome RNA and polymerase, which plays the most essential role in virus proliferation cycle. However, the mechanism of EBOV RNP formation remains unclear. In this work, we solved the high resolution structure of core domain of EBOV NP. The polypeptide of EBOV NP core domain （NPcore） pos- sesses an N-lobe and C-lobe to clamp a RNA binding groove, presenting similarities with the structures of the other reported viral NPs encoded by the members from Mononegavirales order. Most strikingly, a hydrophobic pocket at the surface of the C-lobe is occupied by an a- helix of EBOV NPcore itself, which is highly conserved among filoviridae family. Combined with other bio- chemical and biophysical evidences, our results provides great potential for understanding the mechanism underlying EBOV RNP formation via the mobility of EBOV NP element and enables the development of antiviral therapies targeting EBOV RNP formation.
基金the Major Projects of Science and Technology in Tianjin(No.18ZXJMTG00020).
文摘Triboelectric nanogenerator(TENG)can realize a variety of mechanical energy collections in the environment,which has great potential in the field of wearable energy.However,many TENGs could rarely be satisfactory to wearable electronics promotion because of their expensive raw materials and complex manufacturing processes.In this study,a type of porous structure carbon powder/manganese dioxide(C/MnO_(2))nanocomposite is introduced.The material adopts low-cost,high-yield carbon powder,can be prepared in one step through a simple,economical,and environmentally friendly hydrothermal preparation process,and has high economic practicality.Superior power generation performance was obtained by modulating the charge trapping ability and storage capacity of polydimethylsiloxane@C/MnO_(2)(PDMS@C/MnO_(2))film based on variations in the weight-loading of C/MnO_(2).The maximum output voltage of carbon powder/manganese dioxide TENG(CM-TENG)is 63 V,which is 2.1 times that of PDMS-TENG and 1.86 times that of carbon powder TENG(C-TENG)and can easily light up 53 LEDs.Furthermore,CM-TENG can convert biological motion energy into electrical signals to detect human hand movements.The CM-TENG self-powered system can successfully drive various microelectronic devices,such as electronic watches,liquid crystal displays(LCDs),and calculators.This study provides a reliable,low-cost,high-performance,and widely applicable electronic system that shows great potential in future fields such as wearable devices and micro-sensing systems.
基金Innovation Funding in Shanghai(Nos.20JC1418600 and 18JC1413100)National Nature Science Foundation of China(Nos.82071262 and 81671326)+2 种基金Natural Science Foundation of Shanghai(Nos.20ZR1427200 and 20511101900)Shanghai Municipal Science and Technology Major Project(No.2017SHZDZX01)Shanghai Leading Academic Discipline Project(No.B205).
文摘Objective: This study aimed to investigate the association between single-nucleotide polymorphisms (SNPs) ofPCSK1 (proprotein convertase subtilisin/kexin type 1) related to obesity and nonalcoholic fatty liver disease (NAFLD).Methods: In this case-control observational study, four candidate SNPs (rs6234, rs155971, rs6232, rs3811951) ofPCSK1 were genotyped in 732 NAFLD patients and 823 healthy control participants, all of whom were of ethnic Han Chinese descent. All participants came from Shanghai, China, and joined our study during 2015 to 2016. The frequencies of each allele and genotype, paired linkage disequilibrium, and haplotype were calculated on the SHEsis platform. In addition to SHEsis, five different genetic models (codominant, dominant, recessive, overdominant, and log-additive) were employed to identify the correlation between genotype frequency and NAFLD. This study was approved by the Medical Ethics Committee of Shanghai University of Traditional Chinese Medicine (approved No. 2017LCSY069).Results: In a comparison of NAFLD patients and healthy participants, none of the fourPCSK1 SNPs were significantly correlated with the occurrence of NAFLD (P>0.05), in either genotypic or allelic distribution. The recessive model of rs3811951 appeared to show a correlation (odds ratio=1.077;95% confidence interval=0.924-1.256;P=0.04), but there was no statistical significance after Bonferroni correction (Pcorr>0.0125).Conclusions: Four obesity-relatedPCSK1 SNPs (rs6234, rs155971, rs6232, rs3811951) showed no significant correlation with the development of NAFLD in a Han Chinese population.
