BACKGROUND:The development of tissues and organs in the body is a precise and autonomously regulated process,and the function of biomechanical factors at this macroscale is a basic scientific question worth exploring. OBJECTIVE:To investigate the roles of cell mechanics in morphogenesis of the lobular organoid of 3D Madin-Darby canine kidney(MDCK). METHODS:The formation of MDCK lobular organoid was visualized by fluorescence resonance energy transfer technology,and the influence of different cellular mechanical signals and extracellular matrix environment on lobular organoid formation and corresponding changes in extracellular regulated protein kinases(ERK)activity were examined. RESULTS AND CONCLUSION:(1)Inhibition of ERK signaling pathway can inhibit the growth of MDCK lobular organoid.(2)Inhibition of cell contractile force signals such as ROCK pathway and Myosin Ⅱ activity,reduced ERK activity and lobular organoid size.(3)Selective inhibition of calcium channels in plasma membrane and endoplasmic reticulum led to reduced ERK activity and lobular organoid growth.(4)By inhibiting the mechanically-sensitive receptor Piezo ion channel or integrin signal on the cell membrane,the lobular organoid became smaller or MDCK cells could not generate tissue morphology.(5)Extracellular matrix compositions affected the morphogenesis of lobular organoid.The addition of type I collagen in Matrigel changed the lobular organoid to elongated shape.(6)The results of this study preliminarily show that mechanical signals in the cells and extracellular matrix environment play an important role in culturing MDCK lobular organoid,and provides certain molecular mechanisms.

Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.

Mechanical ventilation(MV)provides life support for critically ill respiratory patients,but in the meantime can cause fatal ventilator-induced lung injury(VILI),and the latter remains a major challenge in respiratory and critical care medicine,because the pathological mechanism has not been fully elucidated.Recent studies show that on the one hand,in the lung with VILI,there exists airway collapse at multi-sites of an individual airway,which can not be explained by traditional airway collapse models.But on the other hand,under MV conditions,airway smooth muscle cells(ASMC)exhibit abnormal mechanical behaviors,accompanied by regulation of Piezo1 expression and endoplasmic reticulum stress.These phenomenons indicate that the MV-induced abnormal mechanical behavior of ASMC is closely related to multiple airway collapse and VILI.Therefore,by studying the MV-induced changes of ASMC mechanical behaviors and their relationship with airway collapse in lung injury,as well as the related mechanochemical signal coupling process,it is expected to reveal a novel mechanism of MV-associated airway collapse and lung injury from the perspective of cell mechanics.In this review,the recent research progress of airway collapse during MV,the regulation of ASMC mechanical behavior by MV-related high stretch,especially the related mechanochemical signal coupling mechanism is summarized.These advances may provide a novel insight for exploring the roles of ASMC abnormal mechanical behavior in the pathological mechanism of VILI,alternative targets of drug intervention for prevention and treatment of VILI,as well as for optimizing the ventilation mode in clinical practice.

Objective To prepare decellularized scaffolds from rabbit cartilage at various concentrations and assess their physicochemical properties and compatibility with stem cells to provide an experimental basis for cartilage repair.Methods Bone marrow mesenchymal stem cells(BMSCs)were cultured using the Percoll density gradient separation method,and this was followed by flow cytometric analysis and testing of their osteogenic and chondrogenic differentiation capabilities.Cartilage pieces were excised from rabbit knees and hip joints and subjected to physical crushing,repeated freeze-thaw cycles,and mixed enzymatic digestion for decellularization.To compare and observe the physicochemical properties of the decellularized scaffolds at different concentrations,three groups of scaffolds(labelwd A,B,and C)were designed with concentrations of 100％,50％and 30％,with three replicates each.Third-generation PKH26-labeled BMSCs were seeded onto optimally concentrated scaffolds and cultured for 1 week to observe cell growth.Results Flow cytometry detected BMSC surface antigens with positive expression of CD44 and CD90 and negative expression of CD45.Osteogenic induction stained with alizarin red showed red calcific nodules,and chondrogenic induction stained with alcian blue showed blue cartilaginous nodules.No apparent cell morphology was observed in the three groups of scaffolds stained with hematoxylin-eosin,and toluidine blue.There was a significant difference in DNA concentration between decellularized samples and non-decellularized scaffolds(P＜0.05).The content of glycosaminoglycans was slightly lower than the normal values.Significant differences were observed between the three groups of scaffolds in terms of pore size,water absorption,porosity,tensile strength,and Young's modulus(P＜0.05).After co-cultivation of stem cells with the scaffolds,cell adhesion was found to be good.Conclusions Percoll density gradient separation can obtain high-purity rabbit BMSCs,and the mixed decellularization method is superior.Group B scaffolds were the most suitable for tissue-engineered cartilage repair.BMSCs cultured in vitro grew well on Group B scaffolds.

Objective To investigate the molecular mechanism of palmitoylation modification in regulating the activity of non-receptor tyrosine kinase Fyn. Methods The intracellular Fyn activity was detected by applying fluorescence resonance energy transfer (FRET) technology, and the mechanism was investigated by combining with Fyn palmitoylation deficiency and C-terminal Src kinase ( CSK ) plasmid co-expression. ResultsExperimental data showed that single loss of either of ( C3, C6) palmitoylation sites resulted in higher Fyn activity, and C6 seemed more significant. It is known that CSK membrane translocation occurred after activation. FRET assay confirmed that CSK could down-regulate the activity of Fyn in cells, but could not effectively regulate the activity of Fyn(GSS) with the loss of palmitoylation sites. Conclusions The results in this study support the hypothesis on Fyn regulation by spatial localization, namely, non-palmitoylated Fyn (GSS) is less effective in the inhibitory regulation by CSK on cell membrane, thus promoting constitutive high activity expression

The critically ill coronavirus disease 2019 (Covid-19) patients usually present acute respiratory distress syndrome (ARDS), or even acute respiratory failure, and require mechanical ventilation (MV) to provide support for breathing. However, clinical studies have found an extraordinarily high mortality rate (>50%) for those Covid-19 patients who underwent MV. Considering the mechanical nature of MV, the high mortality rate is highly possible to be associated with mechanical stretch-induced lung injury during MV. Thus, it is imperative to understand the MV-induced pathological alterations in the respiratory system and corresponding mitigation measures in order to improve the therapy of critically ill Covid-19 patients. Ventilator-induced lung injury in therapy of critically ill Covid-19 patients involves several biomechanical factors and mechanisms, including changes in respiratory parameters, inflammatory cytokines storm, ciliary-mucus system, airway smooth muscle cells, lung fibrosis, and stretch-activated cell signaling. It is hoped that these biomechanical issues can be diligently investigated, so as to provide insights for optimizing the therapy for Covid-19 as well as other respiratory diseases.

This study aimed to evaluate the effect of sanguinarine on biomechanical properties of rat airway smooth muscle cells (rASMCs) including stiffness, traction force and cytoskeletal stress fiber organization. To do so, rASMCs cultured were treated with sanguinarine solution at different concentrations (0.005~5 μmol/L) for 12 h, 24 h, 36 h, and 48 h, respectively. Subsequently, the cells were tested for their viability, stiffness, traction force, migration and microfilament distribution by using methylthiazolyldiphenyl-tetrazolium bromide assay, optical magnetic twisting cytometry, Fourier transform traction microscopy, scratch wound healing method, and immunofluorescence microscopy, respectively. The results showed that at concentration below 0.5 μmol/L sanguinarine had no effect on cell viability, but caused dose and time dependent effect on cell biomechanics. Specifically, rASMCs treated with sanguinarine at 0.05 μmol/L and 0.5 μmol/L for 12 and 24 h exhibited significant reduction in stiffness, traction force and migration speed, together with disorganization of the cytoskeletal stress fibers. Considering the essential role of airway smooth muscle cells (ASMCs) biomechanics in the airway hyperresponsiveness (AHR) of asthma, these findings suggest that sanguinarine may ameliorate AHR via alteration of ASMCs biomechanical properties, thus providing a novel approach for asthma drug development.

Objective: To investigate the prevalence of hypercholesterolemia among Chinese adults in different geographic areas, and to analyze the related factors. Methods: China Chronic and Non-Communicable Disease and Risk Factor Surveillance was conducted in 2013, based on 298 counties/districts in 31 provinces of Chinese mainland. The adults aged 18 years old were randomly selected using multi-stage stratified clustering sampling method. Information on chronic disease and risk factors was collected using face-to-face questionnaire interview and physical measurement. Blood samples were collected by local staffs. Serum total cholesterol (TC) was determined using standard method in a central laboratory. After excluding 565 participants missing key variables and 1 558 participants with abnormal TC values, a total of 174 976 participants were included. Weighted prevalence of hypercholesterolemia was calculated. Hypercholesterolemia related individual or geographic determinants were defined using multilevel logistic regression. Results: The prevalence of hypercholesterolemia in Chinese adults age 18 years old and above was 6.9% (95%CI: 6.4%-7.3%), ranged from 3.0% (95%CI: 2.5%-3.4%) in the northwest of China to 14.2% (95%CI: 12.9%-15.5%) in the south (χ²=183.42, P<0.001). The prevalence of hypercholesterolemia was higher in 6 provinces including Tianjin, Liaoning, Fujian, Guangdong, Guangxi, and Hainan (≥9.0%), but lower in 7 provinces including Shanxi, Shannxi, Gansu, Qinghai, Ningxia, Xinjiang, and Tibet (<3.9%). There was a 1.27 fold variation in hypercholesterolemia prevalence by provincial level, and 72.5% of the geographical variation in hypercholesterolemia prevalence was account for by area-level determinants. With multilevel logistic analysis, the individual risk factors associated with hypercholesterolemia included aging, higher education level or annual household income per capita, regular drinking, too much red meal intake, inactivity, overweight or obesity. For geographic factors, residents living at south China, counties/districts with higher urbanization rates, higher education level or lower standardized death rates were more likely to have hypercholesterolemia (all P<0.05). Conclusion The prevalence of hypercholesterolemia was high in Chinese adults, it was different between regions and related with characteristics of population, individual behaviors and geographical regions.

OBJECTIVE:To study the antioxidant activity of the different polar parts from Dictamnus dasycarpus and its ef-fects on tyrosinase activity. METHODS:Extract was extracted by 95% ethanol from D. dasycarpus,using petroleum ether,chloro-form,ethyl acetate to obtain different polar parts after dissolved in water. 1,1-diphenyl-2-trinitrophenylhydrazine (DPPH) method was used to investigate its antioxidant activity [expressed as half inhibitory concentration (IC50)],and tyrosinase method was used to investigate the related activity in different polar parts. RESULTS:The IC50 of petroleum ether,chloroform,ethyl acetate parts for scavenging DPPH free radicals were 0.875,0.824,0.407 mg/mL,respectively. When the mass concentration of each polar part were 25.0,50.0,100,200,300,400,500 μg/mL,the inhibition rate of petroleum ether part to tyrosinase were -3.18%,-4.98%,0.160%,0.044%,2.31%,3.89%,4.29%;that of trichloromethane part were -33.39%,-31.48%,-10.14%,-5.42%,-9.70%,-4.06%,-0.42%;and that of ethyl acetate part were -17.63%,-17.89%,-18.42%,-21.84%,-20.26%,-22.13%,-32.36%. CONCLUSIONS:The capacity in scavenging DPPH free radicals in ethyl acetate part is obvi-ously stronger than the other 2 parts,showing positive correlation with the concentration. Ethyl acetate and chloroform chave an ac-tivation effect on tyrosinase,the activation effect of chloroform part on tyrosinase was negatively correlated with the concentration and petroleum ether part has a two-way regulatory effect on the activity of tyrosinase.

Objective To comprehensively analyze the disease burden of drowning in the Chinese population both at the national and provincial levels in 1990 and 2013,to provide reference for the development of strategies regarding drowning prevention.Methods Both methods related to unified measurement framework and standardized estimation on Global Burden of Disease in 2013,were used.Data on deaths caused by injuries were from the following sources which include:Disease Surveillance Points,the National Maternal and Child Health Surveillance Network,the Death Registration Reporting System of Chinese Center for Disease Control and Prevention,Death Registration System and death information from Macau and Hong Kong areas of China.Injury-related incidence data was from the National Injury Surveillance System and literature review.Parameters as death/death rate,years of life lost due to premature mortality (YLL)/standardized YLL rate,years living with disability (YLD)/standardized YLD rate and disability-adjusted of life years (DALY)/standardized DALY were used to analyze the disease burden and changing trend on drowning at both the national and all the provincial levels.Results In 2013,the number of deaths due to drowning was 63 619 in China,with the standardized mortality rate as 5.29 per 100 000,accounting for 8.0％ of the total injury deaths.Drowning was the fourth leading cause of injury death in the whole population and the first leading cause of injury death among children aged ＜ 5 and 5-14 years old in 2013,with YLL of drowning as 3.49 million person years,YLD as 0.04 million person years,and DALY as 3.53 million person years.Compared with data from 1990,the rates on standardized mortality,standardized YLL,standardized YLD and standardized DALY of drowning all declined in 2013.The five provinces/districts/cities with the highest rates of drowning were Xinjiang (10.08 per 100 000),Jiangxi (8.44 per 100 000),Anhui (7.92 per 100 000),Guizhou (7.77 per 100 000) and Sichuan (7.68 per 100 000).Standardized mortality of drowning reduced in all provinces in 2013.Conclusions Disease burden of drowning in the Chinese population,especially in children,declined significantly in 2013,comparing to 1990.However,drowning remains a serious proble,with children and males in particular,in China.Research regarding prevention on drowning is in great need in the western and central areas where drowning mortalities appeared high.