Effects of loneliness and isolation on cardiovascular diseases:a two sample Mendelian Randomization Study

BACKGROUND Loneliness and isolation are associated with multiple cardiovascular diseases(CVDs),but there is a lack of research on whether they were causally linked.We conducted a Mendelian Randomization(MR)study to explore causal relationships between loneliness and isolation and multiple CVDs.METHODS Single nucleotide polymorphisms associated with loneliness and isolation were identified from a genome-wide association study(GWAS)of 455,364 individuals of European ancestry in the IEU GWAS database.Summary data for 15 CVDs were also obtained from the IEU GWAS database.We used three MR methods including inverse variance weighting,MR-Egger,and weighted median estimation to assess the causal effect of exposure on outcomes.Cochran's Q test and MR-Egger intercept test were used to evaluate the heterogeneity and pleiotropy.RESULTS MR analysis showed that loneliness and isolation were significantly associated with essential hypertension(OR=1.07,95%CI:1.03-1.12),atherosclerotic heart disease(OR=1.04;95%CI:1.02-1.06),myocardial infarction(OR=1.02;95%CI:1-1.04)and angina(OR=1.04;95%CI=1.02-1.06).No heterogeneity and pleiotropy effects were found in this study.CONCLUSIONS Causal relationship of loneliness and isolation with CVDs were found in this study.

Achieving high strength-ductility synergy in a Mg_(97)Y_(1)Zn_(1)Ho_(1) alloy via a nano-spaced long-period stacking-ordered phase

Achieving high strength in Mg alloys is usually accompanied by ductility loss.Here,a novel Mg97Y1Zn1Ho1 at.%alloy with a yield strength of 403 MPa and an elongation of 10%is developed.The strength-ductility synergy is obtained by a comprehensive strategy,including a lamella bimodal microstructure design and the introduction of nano-spaced solute-segregated 14H long-period stacking-ordered phase(14H LPSO phase)through rare-earth Ho alloying.The lamella bimodal microstructure consists of elongated un-recrystallized(un-DRXed)coarse grains and fine dynamically-recrystallized grains(DRXed regions).The nano-spaced solute-segregated 14H LPSO phase is distributed in DRXed regions.The outstanding yield strength is mainly contributed by grain-boundary strengthening,18R LPSO strengthening,and fiberlike reinforcement strengthening from the nano-spaced 14H LPSO phase.The high elongation is due primarily to the combined effects of the bimodal and lamellar microstructures through enhancing the work-hardening capability.

Glycyrrhizic Acid Protects Glomerular Podocytes Induced by High Glucose by Modulating SNARK/AMPK Signaling Pathway

Objective:Diabetic nephropathy is one of the most important microvascular complications of diabetes,which mainly refers to glomerular capillary sclerosis.Podocytes are an important part of glomerular capillaries.Previous clinical and basic studies have shown that fibrosis is the main factor of diabetic nephropathy.This study aimed to assess the protective mechanism of glycyrrhizic acid(GA)on glomerular podocytes induced by high glucose as we hypothesized that GA may have antifibrotic and anti-inflammatory effects on podocytes through regulation of the adenosine 5'-monophosphate-activated protein kinase(AMPK)/sucrose nonfermenting AMPK-related kinase(SNARK)signaling pathway.Methods:SNARK siRNA was used to transfect podocytes.Real-time quantitative polymerase chain reaction and immunofluorescence staining assays were used for molecular and pathological analysis.The expression levels of key pathway proteins(including TGF-β1,α-SMA,SITR1,AMPKα,LKB1,PGC-1α,NF-κB,IL-6,and TNF-α)were verified by Western blotting.The expression of inflammatory factors in podocytes was detected by ELISA.Results:We demonstrated that GA decreased the expression of podocyte fibrosis signaling pathway-related factors by upregulating the AMPK pathway and its related factors.However,after transfection of podocytes with SNARK siRNA,there was an increased expression of fibrosis-related factors and inflammation-related factors.Conclusion:GA can protect podocytes and alleviate fibrosis and inflammation induced by high glucose,which is related to the AMPK signaling pathway.Meanwhile,knockdown of SNARK protein can inhibit the AMPK signaling pathway,aggravate fibrosis,and increase inflammation.

A putative bHLH transcription factor is a candidate gene for male sterile 32,a locus affecting pollen and tapetum development in tomato

The tomato(Solanum lycopersicum)male sterile 32(ms32)mutant has been used in hybrid seed breeding programs largely because it produces no pollen and has exserted stigmas.In this study,histological examination of anthers revealed dysfunctional pollen and tapetum development in the ms32 mutant.The ms32 locus was fine mapped to a 28.5 kb interval that encoded four putative genes.Solyc01g081100,a homolog of Arabidopsis bHLH10/89/90 and rice EAT1,was proposed to be the candidate gene of MS32 because it contained a single nucleotide polymorphism(SNP)that led to the formation of a premature stop codon.A codominant derived cleaved amplified polymorphic sequence(dCAPS)marker,MS32D,was developed based on the SNP.Real-time quantitative reverse-transcription PCR showed that most of the genes,which were proposed to be involved in pollen and tapetum development in tomato,were downregulated in the ms32 mutant.These findings may aid in marker-assisted selection of ms32 in hybrid breeding programs and facilitate studies on the regulatory mechanisms of pollen and tapetum development in tomato.

The Study on Community Health Education of Empty Nest Elderly

Objective:To study the demands of community health education on the empty nest elderly and analyse the related factors. Methods:The 36-Item Short-Form Health Survey(SF-36), activities of daily living (ADL) and the community health services satisfaction scale were used to investigate the community health service demand and supply of 358 empty nesters. Results:The results showed that the ability of self-care was worse and needed more nursing or caring from others in the empty nest elderly;the empty nest elderly, in comparison with the non-empty-nest elderly, had lower physical and mental scores. With the age changing, the requirements of community health services were different in empty nest elderly and the satisfaction of community health service was low in the empty nest (39.1%). Conclusions: Empty nest elderly generally needed the different degree of community health education demands. The utilization rates of community health education were low.

Neuropathy and chloracne induced by 3,5,6-trichloropyridin-2-ol sodium:Report of three cases

BACKGROUND Chloracne is a rare skin condition that is caused by systemic exposure to halogenated aromatic compounds.The main characteristic of chloracne is blackhead,and in severe cases,it can be accompanied by systemic symptoms.Sodium 3,5,6-trichloropyridin-2-ol(STCP)is a necessary precursor compound for the production of chlorpyrifos and triclopyr,which are extensively used as a pesticide and herbicide,respectively.STCP is also a chlorophenol that has been associated with chloracne.STCP poisoning could induce mild myelin sheath damage.We herein report three cases with chloracne due to exposure to STCP.CASE SUMMARY Three young men,aged 29,33,and 26 years,respectively,in the same workplace had polymorphic skin lesions,characterized mainly by comedones and cysts,and one of them also had acne like lesions in the genital area.These clinical manifestations appeared when they were exposed to STCP for 3 d,1 wk,and 2 wk,respectively.Among them,polyneuropathy and liver damage occurred.We performed dermoscopy and clinical and laboratory tests on these patients.Additionally,histopathology was used for further diagnosis in the serious patient.These patients were diagnosed with chloracne and separated from STCP.The patients were prescribed oral viaminate capsules,topical adapalene gel,and regular hematologic follow-up for aspartate transaminase and lipids.They are still under follow-up.There was no new lesions and the laboratory tests returned to normal in two patients.Pigmentation and shallow scars remained in the original areas of papules.However,in the most serious patient,new papules still appeared intermittently.All these remind us that the treatment of chloracne caused by STCP is difficult,and we should attach great importance to this new compound related with the neuropathy and chloracne.CONCLUSION STCP is becoming a new chemical product to induce chloracne,which should attract the attention of all medical professionals,especially dermatologists.Due to the lack of knowledge on the new chemical,the diagnosis of chloracne cannot be made in time.Chloracne still deserves our attention.

Organic polaritonic light-emitting diodes with high luminance and color purity toward laser displays

Achieving high-luminescence organic light-emitting devices(OLEDs)with narrowband emission and high color purity is important in various optoelectronic fields.Laser displays exhibit outstanding advantages in next-generation display technologies owing to their ultimate visual experience,but this remains a great challenge.Here,we develop a novel OLED based organic single crystals.By strongly coupling the organic exciton state to an optical microcavity,we obtain polariton electroluminescent(EL)emission from the polariton OLEDs(OPLEDs)with high luminance,narrow-band emission,high color purity,high polarization as well as excellent optically pumped polariton laser.Further,we evaluate the potential for electrically pumped polariton laser through theoretical analysis and provide possible solutions.This work provides a powerful strategy with a material–device combination that paves the way for electrically driven organic single-crystal-based polariton luminescent devices and possibly lasers.

经济政策不确定性与年报风险信息披露

随着外部环境不确定性的增加,投资者对风险信息的需求日益增多,而中国上市公司年报风险信息披露呈现较大差异,探讨其动因对于鼓励企业披露风险信息具有重要意义。基于此,文章从经济政策不确定性视角,考察不确定性环境下公司年报风险信息披露的动机及效果。利用2007-2019年A股上市公司年报风险信息披露的文本数据,研究发现,经济政策不确定性与年报风险信息披露显著正相关;当经济政策不确定性提高时,基础风险高的公司选择披露更多的总体风险信息和宏观风险信息,融资约束大的公司选择增加总体风险信息披露。进一步研究发现,经济政策频繁波动将加剧资本市场的信息不对称程度,表现为买卖价差和股价崩盘风险的显著增加,此时公司选择披露更多风险信息有助于缓解不确定性引发的信息不对称。研究对于理解经济政策不确定性环境下公司年报风险信息披露行为及其经济后果具有启示意义。

Visible light assisted enzyme-photocatalytic cascade degradation of organophosphorus pesticides

The worldwide application of organophosphorus pesticides(OPs)has promoted agricultural development,but their gradual accumulation in soil and water can seriously affect the central nervous system of humans and other mammals.Organophosphorus hydrolase(OPH)is an effective enzyme that can catalyze the degradation of the residual OPs.However,the degradation products such as p-nitrophenol(p-NP)is still toxic.Thus,it is of great significance to develop a multi-functional support that can be simultaneously used for the immobilization of OPH and the further degradation of p-NP.Herein,a visible light assisted enzyme-photocatalytic integrated catalyst was constructed by immobilizing OPH on hollow structured Au-TiO_(2)(named OPH@H-Au-TiO_(2))for the degradation of OPs.The obtained OPH@H-Au-TiO_(2)can degrade methyl parathion to p-NP by OPH and then degrade p-NP to hydroquinone with low toxicity by using H-Au-TiO_(2)under visible light.OPH molecules were immobilized on HAu-TiO_(2)through adsorption method to prepare OPH@H-Au-TiO_(2).After 2.5 h of reaction,methyl parathion is completely degraded,and about 82.64%of the generated p-NP is further degraded into hydroquinone.After reused for 4 times,the OPH@H-Au-TiO_(2)retains more than 80%of the initial degradation activity.This research presents a new insight in designing and constructing multi-functional biocatalyst,which greatly expands the application scenarios and industrial value of enzyme catalysis.

Phytoene synthases 1 modulates tomato fruit quality through influencing the metabolic flux between carotenoid and flavonoid pathways

The deterioration in fruit quality of commercial tomatoes is a major concern of modern tomato breeding.However,the metabolism and genetics of fruit quality are poorly understood.Here,we performed transgenic and molecular biology experiments to reveal that tomato phytoene synthase 1(SlPSY1)is responsible for the accumulation of an important flavor chemical,6-methyl-5-hepten-2-one(MHO).To dissect the function of SlPSY1 in regulating fruit quality,we generated and analyzed a dataset encompassing over 2000 compounds detected by GC-MS and LC-MS/MS along with transcriptomic data.The combined results illustrated that SlPSY1 deficiency imparts novel flavor to yellow tomatoes with 236 volatiles significantly changed and improves fruit firmness,possibly due to accumulation of seven cutins.Further analysis indicated SlPSY1 is essential for carotenoid-derived metabolite biosynthesis by catalyzing prephytoene-PP(PPPP)to 15-cis-phytoene.Notably,we showed that SlPSY1 can influence the metabolic flux between carotenoid and flavonoid pathways,and this metabolic flux was confirmed by silencing SlCHS1.Our study provided insights into the multiple effects of SlPSY1 on tomato fruit metabolome and highlights the potential to produce high-quality fruit by rational design of SlPSY1 expression.

A viral protein orchestrates rice ethylene signaling to coordinate viral infection and insect vector-mediated transmission

Arthropod-borne viruses cause serious threats to human health and global agriculture by rapidly spreading via insect vectors. Southern rice black-streaked dwarf virus (SRBSDV) is the most damaging rice-infecting virus that is frequently transmitted by planthoppers. However, the molecular mechanisms underlying its propagation in the host plants and epidemics in the field are largely unknown. Here, we showed that the SRBSDV-encoded P6 protein is a key effector that regulates rice ethylene signaling to coordinate viral infection and transmission. In early SRBSDV infection, P6 interacts with OsRTH2 in the cytoplasm to activate ethylene signaling and enhance SRBSDV proliferation;this also repels the insect vector to reduce infestation. In late infection, P6 enters the nucleus, where it interacts with OsEIL2, a key transcription factor of ethylene signaling. The P6-OsEIL2 interaction suppresses ethylene signaling by preventing the dimerization of OsEIL2, thereby facilitating viral transmission by attracting the insect vector. Collectively, these findings reveal a novel molecular mechanism by which an arbovirus modulates the host defense system to promote viral infection and transmission.

Overview of the systematic reviews of premature ovarian insufficiency treated with acupuncture

Objective:To assess the reliability of the methodological quality and outcome measures of systematic reviews(SR)/meta-analysis of premature ovarian insufficiency(POI) treated with acupuncture.Methods:SR/meta-analysis of POI treated with acupuncture were searched on POI from the databases including PubMed,Web of Science,EMBase,the Cochran Library,Chinese biomedical literature database(SinoMed),China journal full-text database(CNKI),Wanfang data knowledge service platform(Wanfang)and VIP information Chinese periodical service platform(VIP),from inception to 1 st May 2021.Using A Measurement Tool to Assess Systematic Reviews 2(AMSTAR 2) scale and Grades of Recommendations Assessment,Development and Evaluation(GRADE) system,the methodological quality and outcome measures of the included studies were appraised.Results:Ten articles of SR/meta-analysis were included,published from 2015 to 2020.Using AMSTAR 2,5 articles of SR/meta-analysis were rated as critical low quality in methods,3 articles as low quality,and2 articles as moderate quality.The results of GRADE showed that among the 50 outcomes the quality of evidence of 22 outcomes was very low,that of 25 outcomes was low and that of 3 outcomes was moderate.Conclusion:The methodological quality and the reliability of outcome measures were not high in existing SR/meta-analysis on POI treated with acupuncture,which may affect the translation of the SR/metaanalysis findings into clinical practice.It is necessary to further strengthen the methodological quality and reporting standard of SR/meta-analysis,as well as the robustness of design and implementation of randomized controlled trials(RCTs),in order to generate high quality evidences for clinical decision-making and practice.

Whole genome analyses reveal significant convergence in obsessive-compulsive disorder between humans and dogs

Obsessive-compulsive disorder(OCD)represents a heterogeneous collection of diseases with diverse levels of phenotypic,genetic,and etiologic variability,making it difficult to identify the underlying genetic and biological mechanisms in humans.Domestic dogs exhibit several OCD-like behaviors.Using continuous circling as a representative phenotype for OCD,we screened two independent dog breeds,the Belgian Malinois and Kunming Dog and subsequently sequenced ten circling dogs and ten unaffected dogs for each breed.Using population differentiation analyses,we identified 11 candidate genes in the extreme tail of the differentiated regions between cases and controls.These genes overlap significantly with genes identified in a genome wide association study(GWAS)of human OCD,indicating strong convergence between humans and dogs.Through gene expressional analysis and functional exploration,we found that two candidate OCD risk genes,PPP2R2B and ADAMTSL3,affected the density and morphology of dendritic spines.Therefore,changes in dendritic spine may underlie some common biological and physiological pathways shared between humans and dogs.Our study revealed an unprecedented level of convergence in OCD shared between humans and dogs,and highlighted the importance of using domestic dogs as a model species for many human diseases including OCD.

Kāiqiàotōngluòacupuncture combined with repetitive transcranial magnetic stimulation for the treatment of hand dysfunction after stroke

Objective:To observe the clinical improvement of Kāiqiàotōngluò(induce resuscitation and remove obstruction in meridians)acupuncture combined with repetitive transcranial magnetic stimulation(rTMS)in patients with hand dysfunction after stroke,and to provide evidence for its extensive application in the future.Methods:Sixty patients with the problem of hand dysfunction were divided into the observation group and the control group randomly.The two groups of patients were treated with the basic treatment,the observation group received Kdiqiaotongluo acupuncture combined with rTMS,and the control group only received the rTMS treatment.Broetz hand function scale,hemiplegic hand function grading,and modified Barthel index were used to evaluate the hand function of the patients in two groups before and after treatment.Results:After treatment,Broetz score of the patients in observation group and control group were significantly lower than that before treatment,and Broetz score of the patients in observation group was lower than that of control group(all P<0.05);As for the hemiplegic hand function grading,24 cases in the observation group improved,the improvement rate was 80.0%,and 8 cases in the control group improved,the improvement rate was only 26.7%.The improvement rate of observation group was significantly better than that of control group(P<0.01);the Barthel index scores of the observation group and the control group were significantly improved after treatment,and the observation group was better than the control group(both P<0.05).Conclusion:The Kāiqiàotōngluòacupuncture combined with rTMS can improve the hand dysfunction of patients after stroke,and it is worthy of clinical application.

Nocturnal to Diurnal Transition in the Common Ancestor of Haplorrhines:Evidence from Genomic-Scan for Positively Selected Genes

Transition from a nocturnal to a diurnal lifestyle represents a major shift in primate evolution, plays a central role in the adaptation of these species to new habitats, and is involved in modifications to their physiological and social behaviors （Heesy and Ross, 2001; Shultz et al., 2011）. However, two core problems concerning the circadian rhythm transition re- mains unresolved. First, there is controversy concerning the activity pattern of the ancestral primate （Heesy and Ross, 2001; Tan et al., 2005）. Second, the transition process for circadian rhythm in primate evolutionary history is unre- solved. Although most research suggests that primates trans- formed from a nocturnal to a diurnal circadian rhythm in the lineage leading to the common ancestor of the anthropoids or the haplorrhines （anthropoids and tarsier） （Ross, 2000; Heesy and Ross, 2001）, evidence has been insufficient to determine whether this occurred in the lineage leading to the common ancestor of the haplorrhines or the anthroooids.