The bHLH transcription factor CsPIF4 positively regulates high temperature-induced hypocotyl elongation in cucumber

High temperature-induced hypocotyl elongation is a typical thermomorphogenesis trait that may significantly affect early seedling growth and subsequent crop yield.The ambient temperature and endogenous auxin are two critical factors that regulate hypocotyl growth.However,the mechanism of temperature and auxin integration in horticultural plants remains poorly understood.In this study,the roles of the basic helix-loop-helix transcription factor CsPIF4 in regulating auxin biosynthesis genes and the auxin content in the hypocotyl of cucumber(Cucumis sativus L.)seedlings under high temperature were investigated.qRT-PCR and in situ hybridization analysis revealed that expression of CsPIF4 was enhanced in the epidermis and vascular bundles in the hypocotyl of cucumber seedlings in response to high temperature.qRT-PCR and HPLC analysis showed that CsPIF4 positively regulated transcription of the auxin biosynthesis gene CsYUC8 and the auxin content in the hypocotyl under high temperature(35℃).The CRISPR/Cas9-mediated knockout of CsPIF4 resulted in a shorter hypocotyl compared with that of the wild type,together with decreased expression of CsYUC8 and lower auxin content in response to high temperature.Furthermore,biochemical assays showed that CsPIF4 could bind directly to the G-box motif of the CsYUC8 promoter and thereby activate CsYUC8 expression.These findings provide insight into the molecular mechanism of high temperature-mediated hypocotyl elongation in cucumber.

Icariin ameliorates memory deficits through regulating brain insulin signaling and glucose transporters in 3×Tg-AD mice

Icariin,a major prenylated flavonoid found in Epimedium spp.,is a bioactive constituent of Herba Epimedii and has been shown to exert neuroprotective effects in experimental models of Alzheimer’s disease.In this study,we investigated the neuroprotective mechanism of icariin in an APP/PS1/Tau triple-transgenic mouse model of Alzheimer’s disease.We performed behavioral tests,pathological examination,and western blot assay,and found that memory deficits of the model mice were obviously improved,neuronal and synaptic damage in the cerebral cortex was substantially mitigated,and amyloid-βaccumulation and tau hyperphosphorylation were considerably reduced after 5 months of intragastric administration of icariin at a dose of 60 mg/kg body weight per day.Furthermore,deficits of proteins in the insulin signaling pathway and their phosphorylation levels were significantly reversed,including the insulin receptor,insulin receptor substrate 1,phosphatidylinositol-3-kinase,protein kinase B,and glycogen synthase kinase 3β,and the levels of glucose transporter 1 and 3 were markedly increased.These findings suggest that icariin can improve learning and memory impairments in the mouse model of Alzheimer’s disease by regulating brain insulin signaling and glucose transporters,which lays the foundation for potential clinical application of icariin in the prevention and treatment of Alzheimer’s disease.

Newly self-administered two-step tool for screening cognitive function in an ageing Chinese population:an exploratory cross-sectional study

Background Early screening of cognitive function is critical to dementia treatment and care.However,traditional tests require face-to-face administration and are often limited by implementation costs and biases.Aims This study aimed to assess whether the Thoven Cognitive Self-Assessment(TCSA),a novel,innovative two-step touchscreen-based cognition assessment tool,could identify early cognitive impairment due to dementia in older adults.Methods The TCSA was administered to 61 healthy controls(HCs),46 participants with mild cognitive impairment(MCI)and 44 participants diagnosed with dementia recruited from Shanghai.Two outcome measures were generated from the TCSA test:the TCSA_(primary task)score and the TCSA_(secondary task)score.Results The total average scores in the control group for the TCSA_(primary task)and TCSA_(secondary task)were significantly higher than those in the MCI and dementia groups(TCSA_(primary task):HCs vs MCI group vs dementia group,8.58±1.76 vs 5.40±2.67 vs 2.74±2.11,F=75.40,p<0.001;TCSA_(secondary task):HCs vs MCI group vs dementia group,23.02±3.31 vs 17.95±4.93 vs 11.93±5.50,F=76.46,p<0.001).Moreover,receiver operating characteristic analysis showed that a score below 7.5 for the TCSA_(primary task)and a score below 22.5 for the TCSA_(secondary task)were indicators of MCI.Conclusions The TCSA appears to be efficacious for the detection of cognitive impairment in older adults.It demonstrates the potential for large-scale cognition screening in community service settings.

Cucumber malate decarboxylase,CsNADP-ME2,functions in the balance of carbon and amino acid metabolism in fruit

Central metabolism produces carbohydrates and amino acids that are tightly correlated to plant growth and thereby crop productivity.Malate is reported to link mitochondrial respiratory metabolism with cytosolic biosynthetic pathways.Although the function of malate metabolism-related enzymes in providing carbon has been characterized in some plants,evidence for this role in the fleshy fruit of cucumber is lacking.Here,radiolabeled bicarbonate fed into the xylem stream from the cucumber roots was incorporated into amino acids,soluble sugars,and organic acids in the exocarp and vasculature of fruits.The activities of decarboxylases,especially decarboxylation from NADP-dependent malic enzyme(NADP-ME),were higher in cucumber fruit than in the leaf lamina.Histochemical localization revealed that CsNADP-ME2 was mainly located in the exocarp and vascular bundle system of fruit.Radiotracer and gas-exchange analysis indicated that overexpression of CsNADP-ME2 could promote carbon flux into soluble sugars and starch in fruits.Further studies combined with metabolic profiling revealed that the downregulation of CsNADP-ME2 in RNA interference(RNAi)lines caused the accumulation of its substrate,malate,in the exocarp.In addition to inhibition of glycolysis-related gene expression and reduction of the activities of the corresponding enzymes,increased amino acid synthesis and decreased sugar abundance were also observed in these lines.The opposite effect was found in CsNADP-ME2-overexpressing lines,suggesting that there may be a continuous bottom-up feedback regulation of glycolysis in cucumber fruits.Overall,our studies indicate that CsNADP-ME2 may play potential roles in both central carbon reactions and amino acid metabolism in cucumber fruits.

Establishment of image-guided radiotherapy of orthotopic hepatocellular carcinoma mouse model

Background:Hepatocellular carcinoma(HCC)is the most common type of liver cancer.Recently,developments in radiotherapy technology have led to radiotherapy becoming one of the main therapeutics of HCC.Therefore,a suitable animal model for radiotherapy of the orthotopic HCC mouse model is urgently needed.Methods:In the present study,Hepa1-6 cells were injected into the liver of C57BL/6 mice in situ to mimic the pathological characteristics of the original HCC.Tumor formation was monitored by applying magnetic resonance imaging techniques and verified by H&E histopathological staining,AFP staining,and Ki67 staining.A single dose of 10 Gy X-ray was applied to simulate clinical radiotherapy plans using image-guided radiotherapy(IGRT)equipment.The efficiency of radiotherapy was then assessed by examining tumor size and weight one week after radiation.Cleaved-caspase3 staining and TUNEL were used to assess apoptosis in tumor tissues.Results:Intrahepatic tumor development was detected in the liver according using MRI.A high-density shadow could be seen 10 days after cell injection,which indicated the formation of HCC in vivo.The tumors grew steadily bigger,and underwent precision radiotherapy 20 days after injection.The typical pathological characteristics of HCC,such as large,deeply stained nuclei and irregular cell size,were visible with H&E staining.After radiotherapy,significantly higher expression of the immunohistochemical markers Ki67 and AFP were detected in tumor tissue than in the nearby normal tissue.Compared with the control group,the tumor volume(p=0.05)and weight(p<0.05)of the irradiated group were significantly reduced.In addition,a higher frequency of apoptosis was identified in irradiated HCC tumor tissue using the TUNEL and cleaved-caspase3 staining assay.Conclusions:In a well-established orthotopic HCC model,MRI was utilized to monitor the formation of tumors,and IGRT was used to simulate clinical radiotherapy.The present study could provide a suitable preclinical system for HCC radiotherapyrelated studies.

Micro RNAs: Novel immunotherapeutic targets in colorectal carcinoma

Colorectal carcinoma(CRC) is one of the most common types of cancer worldwide and the prognosis for CRC patients with recurrence or metastasis is extremely poor. Although chemotherapy and radiation therapy can improve survival, there are still numerous efforts to be performed. Immunotherapy is frequently used, either alone or in combination with other therapies, for the treatment of CRC and is a safe and feasible way to improve CRC treatment. Furthermore, the significance of the immune system in the biology of CRC has been demonstrated by retrospective assessments of immune infiltrates in resected CRC tumors. Micro RNAs(mi RNAs) are short, non-coding RNAs that can regulate multiple target genes at the post-transcriptional level and play critical roles in cell proliferation, differentiation and apoptosis. Mi RNAs are required for normal immune system development and function. Nevertheless, aberrant expression of mi RNAs is often observed in various tumor types and leads to immune disorders or immune evasion. The immunomodulatory function of mi RNAs indicates that mi RNAs may ultimately be part of the portfolio of anti-cancer targets. Herein, we will review the potential roles of mi RNAs in the regulation of the immune response in CRC and then move on to discuss how to utilize different mi RNA targets to treat CRC. We also provide an overview of the major limitations and challenges of using mi RNAs as immunotherapeutic targets.

Study on Evaluation Method of Aluminum alloy Pulse MIG Welding Stability Based on Arc Voltage Probability Density

Bring forward a new analytical method in order to evaluate the stability of the process of aluminum alloy pulsed MIG welding. The ratio of the first and the second peak in arc voltage signal probability density was selected to evaluate aluminum alloy pulse MIG welding stability. By calculating the arc voltage signal probability density from 80 sets of welding experiments, the ratio of the two peaks in arc voltage probability in every set was captured. And the evaluation system of aluminum alloy pulse MIG welding stability was established. The smaller the ratio of peaks in arc voltage signal probability density is, the better the stability of the welding will be;the bigger the ratio of peaks in arc voltage signal probability density is, the poorer the stability of the welding will be.

Intestinal obstruction due to migration of a thermometer from bladder to abdominal cavity:A case report

Intraperitoneal foreign bodies such as retained surgical instruments can cause intestinal obstruction.However,intestinal obstruction due to transmural migration of foreign bodies has rarely been reported.Here,we report a case of intestinal obstruction due to a clinical thermometer which migrated from the bladder into the abdominal cavity.A 45-year-old man was admitted to our hospital with a one-year history of recurrent lower abdominal cramps.Two days before admission,the abdominal cramps aggravated.Intestinal obstruction was confirmed with upright abdominal radiography and computerized tomography scan which showed dilation of the small intestines and a thermometer in the abdominal cavity.Then laparotomy was performed.A scar was observed at the fundus of the bladder and a ther-mometer was adhering to the small bowels and mesentery which resulted in intestinal obstruction.Abdominal cramps were eliminated and defecation and flatus recovered soon after removal of the thermometer.

Why choose 3D bioprinting?Part Ⅲ:printing in vitro 3D models for drug screening

Dilemmas of current drug screening Recently,multiple technological advancements have been involved in the process of drug research and discovery.In addition,the spending on the relevant projects has doubled in the last 20 years,cumulatively increasing 28%from 2014 to 2016.However,these improvements have not led directly to an obvious increase in feasible drug candidates that successfully passed the clinical trials.According to the increased spending and stagnant clinical success rate of 10–20%,the efficiency of this project drastically decreased from around 40 drugs per billion in 1950 to 0.6 drugs in 2012.

A case of dissociative convulsions presented as frequent epilepsylike seizures

Dissociative convulsions, a prominent form of dissociative (conversion) disorder formerly known as hysteria, are a common and elusive differential diagnosis from epilepsy. However, the treatment of such patients is always challenging and frustrating due to poor response to the routinely used interventions in most situations. Here, we present a case with dissociative convulsions in order to catch the eye of the clinicians and researchers on the recognition of clinical manifestation and exploration of therapeutic strategies.

Rapid and mass manufacturing of soft hydrogel microstructures for cell patterns assisted by 3D printing

Micro-/nano-patterns on hydrogels are widely used in cell patterning.However,manufacturing molds with traditional lithography is time-consuming and expensive.In addition,the excessive demolding force can easily damage patterns since biocompatible hydrogels are ultra-soft or brittle.Here,we presented a novel method for rapid and mass fabrication of cell patterns.High-precision three-dimensional(3D)printing was used to manufacture a mold with a resolution of 2µm,and the gelatin-based hydrogel was cured by thermal–photo-crosslinking so that the low-concentration and low-substitutionrate hydrogel could be demolded successfully.We found that pre-cooling before illumination made gelatin-based hydrogels resilient due to the partial regain of triple-helix structures.With this method,arbitrarily customized hydrogel patterns with a feature size of 6–80µm can be fabricated stably and at low cost.When cardiomyocytes were seeded on ultra-soft hydrogels with parallel groove structures,a consistent and spontaneous beating with 216 beats per minute(BPM)could be observed,approaching the natural beating rate of rat hearts(300 BPM).Overall,this work provides a general scheme for manufacturing cell patterns which has great potential for cell ethology and tissue repair.

Efficacy of comprehensive cognitive health management for Shanghai community older adults with mild cognitive impairment

Background The management of modifiable risk factors and comorbidities may impact the future trajectory of cognitive impairment,but easy-to-implement management methods are lacking.Aims This study investigated the effects of simple but comprehensive cognitive health management practices on the cognitive function of older adults in the community with normal cognition(NC)and mild cognitive impairment(MCI).Methods The comprehensive cognitive health management programme included a psychiatric assessment of the cognitive risk factors for those in the intervention groups and individualised recommendations for reducing the risks through self-management supported by regular medical professional follow-up.The intervention groups for this study included 84 elderly participants with NC and 43 elderly participants with MCI who received comprehensive cognitive health management.The control groups included 84 elderly participants with NC and 43 elderly participants with MCI who matched the intervention group’s general characteristics and scale scores using the propensity matching score analysis.The Montreal Cognitive Assessment(MoCA)scale and Geriatric Depression Scale(GDS)scores were compared after a 1-year follow-up.Results For older adults with MCI in the intervention group,MoCA scores were higher at the 1-year followup than at baseline(24.07(3.674)vs 22.21(3.052),p=0.002).For the MoCA subscales,the intervention group’s abstract and delayed memory scores had significantly increased during the 1-year follow-up.Furthermore,in a generalised linear mixed model analysis,the interaction effect of group×follow-up was statistically significant for the MCI group(F=6.61,p=0.011;coefficients=5.83).Conclusions After the comprehensive cognitive health management intervention,the older adults with MCI in the community showed improvement at the 1-year follow-up.This preliminary study was the first to demonstrate an easy-to-implement strategy for modifying the cognitive risk factors of elderly individuals with MCI in the community,providing new insight into early-stage intervention for dementia.

Effect of Impeller Solidity on the Generating Performance for Solar Power Generation

According to current solar power research,both the generating unit’s minimum start-up speed and power generation system’s minimum flow rate for operation decrease with the increase in the impeller solidity.Ideally,a high solidity should be achieved,as this translates more power for a solar power system in the start-up and shut-down cycles.However,increasing the number of blades does not increase the impeller solidity;therefore,there is an optimal number of blades needed to achieve the preferred solidity.This paper begins by selecting the blade airfoil and then performs a theoretical analysis based on the relationship between the blade number and chord length.Experiments are conducted to measure the starting and stopping wind speeds and power characteristics for different numbers of blades.The results show that a maximum impeller solidity of 0.2862 is achieved,as well as the minimum flow speed at the start-up,and the maintenance of the solar chimney power generation system is optimized when there are four blades.

Melatonin decreases GSDME mediated mesothelial cell pyroptosis and prevents peritoneal fibrosis and ultrafiltration failure

Peritoneal fibrosis together with increased capillaries is the primary cause of peritoneal dialysis failure.Mesothelial cell loss is an initiating event for peritoneal fibrosis.We find that the elevated glucose concentrations in peritoneal dialysate drive mesothelial cell pyroptosis in a manner dependent on caspase-3 and Gasdermin E,driving downstream inflammatory responses,including the activation of macrophages.Moreover,pyroptosis is associated with elevated vascular endothelial growth factor A and C,two key factors in vascular angiogenesis and lymphatic vessel formation.GSDME deficiency mice are protected from high glucose induced peritoneal fibrosis and ultrafiltration failure.Application of melatonin abrogates mesothelial cell pyroptosis through a MT1R-mediated action,and successfully reduces peritoneal fibrosis and angiogenesis in an animal model while preserving dialysis efficacy.Mechanistically,melatonin treatment maintains mitochondrial integrity in mesothelial cells,meanwhile activating m TOR signaling through an increase in the glycolysis product dihydroxyacetone phosphate.These effects together with quenching free radicals by melatonin help mesothelial cells maintain a relatively stable internal environment in the face of high-glucose stress.Thus,Melatonin treatment holds some promise in preserving mesothelium integrity and in decreasing angiogenesis to protect peritoneum function in patients undergoing peritoneal dialysis.

Biomarkers of aging

Aging biomarkers are a combination of biological parameters to(i)assess age-related changes,(ii)track the physiological aging process,and(iii)predict the transition into a pathological status.Although a broad spectrum of aging biomarkers has been developed,their potential uses and limitations remain poorly characterized.An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research:How old are we?Why do we get old?And how can we age slower?This review aims to address this need.Here,we summarize our current knowledge of biomarkers developed for cellular,organ,and organismal levels of aging,comprising six pillars:physiological characteristics,medical imaging,histological features,cellular alterations,molecular changes,and secretory factors.To fulfill all these requisites,we propose that aging biomarkers should qualify for being specific,systemic,and clinically relevant.

J-shaped association between dietary zinc intake and new-onset hypertension:a nationwide cohort study in China

We aimed to investigate the relationship of dietary zinc intake with new-onset hypertension among Chinese adults.A total of 12,177 participants who were free of hypertension at baseline from the China Health and Nutrition Survey were included.Dietary intake was assessed by three consecutive 24-h dietary recalls combined with a household food inventory.Participants with systolic blood pressure≥140 mmHg or diastolic blood pressure≥90 mmHg or diagnosed by a physician or under antihypertensive treatment during the follow-up were defined as having new-onset hypertension.During a median follow-up duration of 6.1 years,4269 participants developed new-onset hypertension.Overall,the association between dietary zinc intake and new-onset hypertension followed a J-shape(P for non-linearity<0.001).The risk of new-onset hypertension significantly decreased with the increment of dietary zinc intake(per mg/day:hazard ratio(HR)0.93;95%confidence interval(CI)0.88–0.98)in participants with zinc intake<10.9 mg/day,and increased with the increment of zinc intake(per mg/day:HR 1.14;95%CI 1.11–1.16)in participants with zinc intake≥10.9 mg/day.In conclusion,there was a J-shaped association between dietary zinc intake and new-onset hypertension in general Chinese adults,with an inflection point at about 10.9 mg/day.

Complicated Bosworth fracture-dislocation:A case report and review of the literature

Bosworth fracture and dislocation is relatively rare,accounting for about 1%of ankle fractures.It is characterized by the proximal fibula fracture embedded in the posterolateral distal tibia.Due to an insufficient understanding of this fracture,it is easy to cause missed diagnosis and misdiagnosis in clinical practice.Due to the insertion of the fracture,it is challenging to perform closed reduction,and improper treatment is easy to cause complications.Surgical treatment is recommended for this type of fracture.In order to improve the understanding of orthopedic surgeons about Bosworth fracture and dislocation,this paper reports the diagnosis and treatment of 2 cases of Bosworth fracture and dislocation,and reviews the literature on Bosworth fracture's mechanism,diagnosis,classification,complications,and treatment options in recent years.

The Smallest Monofluorodiazoethane Reagent and Its[3+2]Cycloaddition Reactions

Given the widespread applications of fluorinated substances in pharmaceuticals,biology,and materials,the development of fluorine-containing building blocks remains an important topic in organic chemistry.In the repertoire of fluorinated diazo compounds,research on tri-and difluorodiazoethane is well-established,but the lack of synthetic methods has left studies related to monofluorodiazoethane as an unexplored territory.In our current work,the taming of the smallest monofluorodiazoethane reagent was realized using two phenylsulfonyl mask groups.This newly synthesized diazo reagent displayed intriguing reactivity patterns:the reaction with aryldiazonium salts gave monofluoromethyl tetrazoles,whereas its reactivity with alkynes and alkenes furnished monofluoromethyl isoxazoles and dihydro-isoxazoles.Furthermore,the removal of the masking groups provided access to a wide range of monofluoromethyl-functionalized heterocycles.

从机会公平走向发展公平——疫情之下我国中小学大规模在线教育的城乡对比分析

面对突发的新冠疫情,2020年上半年我国基础教育全面进入"停课不停学"的在线教育模式。作为本次抗击疫情的应急之举,在线教学在实施中经历了各方考验。本研究面向全国32个省份地区基础教育各学段的学生、教师及教育管理者进行问卷抽样调查,随机发放了42万余份调研问卷,从政策实施、教学组织、学习体验等方面综合了解疫情期间在线教学的实施现状,并从教育均衡的视角对城乡学校应对情况展开对比。结果显示,各地区学校都已基本具备了教育资源公共服务平台等在线教学条件,保障了此次在线教学的顺利开展。但此次疫情危机中学校在个性化决策和教学创新方面普遍存在欠缺,乡村学校在资源获取、在线教学经验以及配套支持上存在不足,城乡学生在学习兴趣与效果、信息技术素养、心理健康程度上差异显著,城乡教师在信息化教学能力上差距较大。基于本次大规模在线教学的开展经验,深入剖析现存教育问题,本文尝试从资源建设、配置优化、智能时代教师与学习公民塑造等角度为未来教育信息化发展提供政策建议。

Interface Hydrogen-bonded Core-Shell Nanofibers by Coaxial Electrospinning

Core-shell nanofibers were prepared by coaxial electrospinning technology,with poly（ethylene oxide）（PEO） as the core while poly（acrylic acid）（PAA） as the shell.PEO and PAA can form polymer complexes based on hydrogen bonding.In order to avoid forming strong hydrogen bonding complexes at nozzle and blocking spinning process,a polar aprotic solvent,N,N-dimethylformamide（DMF）,was selected to dissolve PEO and PAA respectively.SEM,TEM and DSC were utilized to characterize the morphology and structure of PEO-PAA core-shell nanofibers.FTIR spectra demonstrated that hydrogen bonding was formed at the core-shell interface.In addition,the PAA shell of the nanofibers can be cross-linked by ethylene glycol（EG） under heat treatment,which increases the stability and extends the potential applications in aqueous environment.