Differences in Non-suicidal Self-injury Behaviors between Unipolar Depression and Bipolar Depression in Adolescent Outpatients

Objective Non-suicidal self-injury(NSSI)has a higher prevalence in adolescents with depressive disorders than in community adolescents.This study examined the differences in NSSI behaviors between adolescents with unipolar depression(UD)and those with bipolar depression(BD).Methods Adolescents with UD or BD were recruited from 20 general or psychiatric hospitals across China.The methods,frequency,and function of NSSI were assessed by Functional Assessment of Self-Mutilation.The Beck Suicide Ideation Scale was used to evaluate adolescents’suicidal ideation,and the 10-item Kessler Psychological Distress Scale to estimate the anxiety and depression symptoms.Results The UD group had higher levels of depression(19.16 vs.17.37,F=15.23,P<0.001)and anxiety symptoms(17.73 vs.16.70,F=5.00,P=0.026)than the BD group.Adolescents with BD had a longer course of NSSI than those with UD(2.00 vs.1.00 year,Z=−3.39,P=0.001).There were no statistical differences in the frequency and the number of methods of NSSI between the UD and BD groups.Depression(r=0.408,P<0.01)and anxiety(r=0.391,P<0.01)were significantly and positively related to NSSI frequency.Conclusion Adolescents with BD had a longer course of NSSI than those with UD.More importantly,NSSI frequency were positively and strongly correlated with depression and anxiety symptoms,indicating the importance of adequate treatment of depression and anxiety in preventing and intervening adolescents’NSSI behaviors.

A phase separation-fortified bi-specific adaptor for conditional tumor killing

A common approach in therapeutic protein development involves employing synthetic ligands with multivalency,enabling sophisticated control of signal transduction.Leveraging the emerging concept of liquid-liquid phase separation(LLPS)and its ability to organize cell surface receptors into functional compartments,we herein have designed modular ligands with phase-separation modalities to engineer programmable interreceptor communications and precise control of signal pathways,thus inducing the rapid,potent,and specific apoptosis of tumor cells.Despite their simplicity,these“triggers”,named phase-separated Tumor Killers(hereafter referred to as psTK),are sufficient to yield interreceptor clustering of death receptors(represented by DR5)and tumor-associated receptors,with notable features:LLPSmediated robust high-order organization,well-choreographed conditional activation,and broad-spectrum capacity to potently induce apoptosis in tumor cells.The development of novel therapeutic proteins with phase-separation modalities showcases the power of spatially reorganizing signal transduction.This approach facilitates the diversification of cell fate and holds promising potential for targeted therapies against challenging tumors.

Research progress toward the influence of mosquito salivary proteins on the transmission of mosquito-borne viruses

Mosquito-borne viruses(MBVs)are a large class of viruses transmitted mainly through mosquito bites,including dengue virus,Zika virus,Japanese encephalitis virus,West Nile virus,and chikungunya virus,which pose a major threat to the health of people around the world.With global warming and extended human activities,the incidence of many MBVs has increased significantly.Mosquito saliva contains a variety of bioactive protein components.These not only enable blood feeding but also play a crucial role in regulating local infection at the bite site and the remote dissemination of MBVs as well as in remodeling the innate and adaptive immune responses of host vertebrates.Here,we review the physiological functions of mosquito salivary proteins(MSPs)in detail,the influence and the underlying mechanism of MSPs on the transmission of MBVs,and the current progress and issues that urgently need to be addressed in the research and development of MSP-based MBV transmission blocking vaccines.

部分ESCRT亚基通过调控STING的降解调节其活性

Stimulator of interferon genes(STING),also known as MITA,ERIS,MPYS or TMEM173,is a key player in innate immunity,specifically in the typeⅠinterferon response[1-3].It is also involved in a range of non-canonical biological functions,including autophagy,cellular metabolism,translation,and DNA repair,and has implications in many diseases[4-9].After activation by its ligands,STING translocates from endoplasmic reticulum(ER),via ERGIC,Golgi apparatus and endosomes,finally to lysosomes for degradation[4-9].However,the mechanisms by which STING is delivered to lysosomes and whether this delivery process regulates STING activity remain elusive.

The spectrum of rare monogenic diseases in patients with premature coronary artery disease

To the Editor:The global burden of premature coronary artery disease(CAD)is increasing among the young population.Premature CAD generally refers to the occurrence of obstructive coronary atherothrombotic lesions in men and women aged<55 years and<65 years,respectively,and particularly in those aged<45 years.[1]The incidence of CAD in the younger population has remained stable or has increased,despite the declining incidence in older adults.Patients with premature CAD have a poor long-term prognosis,experiencing a high rate of recurrent ischemic events,rapid progression to multivessel disease,and frequent premature death.[1]Thus,it is crucial to identify the underlying causes of premature CAD that are distinct from those of age-related CAD and improve patient outcomes through precise diagnosis and treatment.

Expressing a human RNA demethylase as an assister improves gene-editing efficiency in plants

Dear Editor,Despite myriad successful applications of gene editing in plant functional genomics research and precision breeding,many challenges persist around the efficiency of gene-editing tools for many plant species.For instance,soybean(Glycine max)is a major crop providing oil and protein to human diets and feedstock,but its gene-editing efficiency remains relatively low(Bai et al.,2019).

A Cullin 5-based complex serves as an essential modulator of ORF9b stability in SARS-CoV-2 replication

The ORF9b protein,derived from the nucleocapsid’s open-reading frame in both SARS-CoV and SARS-CoV-2,serves as an accessory protein crucial for viral immune evasion by inhibiting the innate immune response.Despite its significance,the precise regulatory mechanisms underlying its function remain elusive.In the present study,we unveil that the ORF9b protein of SARS-CoV-2,including emerging mutant strains like Delta and Omicron,can undergo ubiquitination at the K67 site and subsequent degradation via the proteasome pathway,despite certain mutations present among these strains.Moreover,our investigation further uncovers the pivotal role of the translocase of the outer mitochondrial membrane 70(TOM70)as a substrate receptor,bridging ORF9b with heat shock protein 90 alpha(HSP90α)and Cullin 5(CUL5)to form a complex.Within this complex,CUL5 triggers the ubiquitination and degradation of ORF9b,acting as a host antiviral factor,while HSP90αfunctions to stabilize it.Notably,treatment with HSP90 inhibitors such as GA or 17-AAG accelerates the degradation of ORF9b,leading to a pronounced inhibition of SARS-CoV-2 replication.Single-cell sequencing data revealed an up-regulation of HSP90αin lung epithelial cells from COVID-19 patients,suggesting a potential mechanism by which SARS-CoV-2 may exploit HSP90αto evade the host immunity.Our study identifies the CUL5-TOM70-HSP90αcomplex as a critical regulator of ORF9b protein stability,shedding light on the intricate host–virus immune response dynamics and offering promising avenues for drug development against SARS-CoV-2 in clinical settings.

Regulation of aerobic glycolysis to decelerate tumor proliferation by small molecule inhibitors targeting glucose transporters

Dear Editor,Different from normal differentiated cells,metabolic reprogramming was spotted in cancer cells,due to increased demand for energy and macromolecule synthesis during their rapid proliferation(Hanahan and Weinberg,2011;Pavlova and Thompson,2016).Most cancer cells prefer anaerobic glycolysis even with oxygen in the environment due to its higher speed to produce macromolecular materials required for biosynthesis(Vander Heiden et al.,2009;DeBerardinis and Chandel,2016).But to compensate for the lower efficiency of anaerobic glycolysis in producing ATP,these cancer cells demand much higher glucose supply(Warburg,1956;Vander Heiden et al.,2009).These metabolic characteristics point to the huge demand of cancer cells for carbohydrate substrates,which creates the possibility of treating tumors by exploiting this feature(Patra et al.,2013;DeBerardinis and Chandel,2016).

Impact of the microbiome on mosquito-borne diseases

Mosquito-borne diseases present a significant threat to human health,with the possibility of outbreaks of new mosquito-borne diseases always looming.Unfortunately,current measures to combat these diseases such as vaccines and drugs are often either unavailable or ineffective.However,recent studies on microbiomes may reveal promising strategies to fight these diseases.In this review,we examine recent advances in our understanding of the effects of both the mosquito and vertebrate microbiomes on mosquito-borne diseases.We argue that the mosquito microbiome can have direct and indirect impacts on the transmission of these diseases,with mosquito symbiotic microorganisms,particularly Wolbachia bacteria,showing potential for controlling mosquito-borne diseases.Moreover,the skin microbiome of vertebrates plays a significant role in mosquito preferences,while the gut microbiome has an impact on the progression of mosquito-borne diseases in humans.As researchers continue to explore the role of microbiomes in mosquito-borne diseases,we highlight some promising future directions for this field.Ultimately,a better understanding of the interplay between mosquitoes,their hosts,pathogens,and the microbiomes of mosquitoes and hosts may hold the key to preventing and controlling mosquito-borne diseases.

肺炎克雷伯菌中同时具有高毒力和碳青霉烯类耐药性的“超级细菌”:这类新兴医院感染病原菌正在中国迅速发展

高毒力肺炎克雷伯菌(hvKP)和碳青霉烯耐药肺炎克雷伯菌(CRKP)是两种引发严重感染的细菌.hvKP通常在年轻健康的人群中引发社区获得性感染,如肝脓肿、眼内炎和脑膜炎.而CRKP则主要与医院获得性感染有关,包括尿路感染、肺炎、败血症和软组织感染.然而,近年来出现了碳青霉烯耐药高毒力肺炎克雷伯菌(CR-hvKP),使得两种细菌之间的界限逐渐模糊.CR-hvKP具有多重耐药性、高毒力和高传播性等特点,对人类健康造成了严重威胁.目前,大多数CR-hvKP的病例报告来自中国等亚洲国家.CR-hvKP的形成机制通常是hvKP或CRKP分别获得携带碳青霉烯耐药基因或毒力基因的质粒,或者两者的杂交质粒而成.该综述概述了CR-hvKP的关键耐药机制、毒力因子、临床表现和预后,并探讨了其在中国的演化过程和流行情况.

Biogenesis of autophagosomes from the ERGIC membrane system

Introduction Macroautophagy(hereafter referred as autophagy)is a process of cellular self-degradation.In response to nutrient deprivation or other stimuli,a nascent double-membrane autophagosome,encapsulating intracellular materials or damaged organelles,is generated.The autophagosome is transported toward and eventually fuses with the lysosome(or the vacuole in yeast and plant cells).

一个金属纳米团簇压缩结构的构筑与转化

尽管已开展了不少金属纳米团簇方面的研究,但表面配体对结构的影响还没有被很好地理解.例如,表面配体的挤压可能对团簇结构产生影响,这一点没有被广泛意识到.我们通过使用具有不同挤压作用的配体来构筑和转化一个新的团簇,对此进行了证实:我们将前期合成中使用的配体3-甲氧基苯硫酚替换成位阻更大(挤压作用更强)的4-叔丁基苯硫酚,获得了比原来(AgCu)_(50)团簇更为压缩的(AgCu)_(27)结构(原子层间距最短达1.21Å).在此基础上,通过与位阻较小的碘离子的交换反应,将(AgCu)_(27)转化为压缩程度相对较轻的Ag_(55)Cu_(8)I_(12)面心立方结构(平均层间距为2.03Å).值得一提的是,引入的碘离子交换转换反应未曾在金属纳米团簇领域报道过,本文证明该转换方法具有一定的普适性,因而不仅为金属纳米团簇的合成(尤其是相对起始团簇尺寸显著增大的团簇的合成),而且为I−的传感提供了一种新的策略.进一步通过理论计算解释了(AgCu)_(27)团簇对卤素离子中I−具有选择性的原因.总之,该工作引入了一种新颖且通用的纳米团簇合成或离子传感策略,为利用配体的物理作用提供了新的视角,并加深了对纳米团簇内核和表面无机配体相互作用的理解.

Mosquito-borne pathogens hijack human body odors to promote transmission

Mosquitoes are one of the world’s deadliest animals,transmitting many diseases including malaria,yellow fever,dengue fever,Zika fever and Chikungunya fever,among others.Over one million deaths per year are attributed to mosquito-borne diseases.Dengue viruses(DENV)cause the most significant arboviral disease.

Flavivirus-infected hosts attract more mosquitoes to bite

Mosquitoes adapt to different habitats and feed on a variety of animals.Anthropophilic female mosquitoes,such as Aedes aegypti and Anopheles gambiae,have a strong innate drive to detect their human hosts and acquire blood meals for their egg production[1].Their biting behavior is not only annoying but also transmits many life-threatening diseases.Aedes aegypti has evolved to specialize in biting humans and is the vector of many mosquito-borne diseases,such as dengue virus(DENV),Zika virus(ZIKV),yellow fever virus(YFV),and chikungunya virus(CHIKV)[2].Anopheles gambiae,the malaria vector,has also developed a preference for humans,which makes it an effective vector for disease transmission.Many mosquito-borne infectious diseases pose an increasing global health threat,and consequently,there is an urgent need to control their transmission.

蚊媒病毒传播和感染的研究进展

Arboviruses,a diverse group of vector-borne pathogens transmitted by various vectors such as mosquitoes,ticks,and flies,encompass members of the Flaviviridae,Togaviridae,Phenuviridae,Peribunyaviridae,Reoviridae,Asfarviridae,Rhabdoviridae,Poxviridae,and Orthomyxoviridae families[1].

RNA biology and therapeutics

Eukaryotic genomes undergo pervasive transcription,generating vast amounts of noncoding RNAs alongside protein-coding mRNAs[1].These noncoding RNAs,including small noncoding RNAs,long noncoding RNAs(lncRNAs),and circular RNAs,have been shown to play critical roles in gene regulation,chromatin remodeling,assembly of membraneless organelles,and other essential biological processes.They function through a diverse range of mechanisms[2],[3],[4],[5].Dysregulation of noncoding RNAs contributes to human disease pathogenesis and affects plant development and stress response[6],[7],[8].Over the past decade,significant progress has been made in unraveling the functions of noncoding RNAs and elucidating the molecular mechanisms by which they operate.The involvement of noncoding RNAs in human disease pathogenesis and agronomic trait regulation has garnered increasing attention.

Atg5 regulates late endosome and lysosome biogenesis

Autophagy is an evolutionarily conserved lysosome-based degradation process.Atg5 plays a very important role in autophagosome formation.Here we show that Atg5 is required for biogenesis of late endosomes and lysosomes in an autophagy-independent manner.In Atg5 cells,but not in other essential autophagy genes defecting cells,recycling and retrieval of late endosomal components from hybrid organelles are impaired,causing persistent hybrid organelles and defective formation of late endosomes and lysosomes.Defective retrieval of late endosomal components from hybrid organelles resulting from impaired recruitment of a component of V1-ATPase to acidic organelles blocks the pH-dependent retrieval of late endosomal components from hybrid organelles.Lowering the intracellular pH restores late endosome/lysosome biogenesis in Atg5 cells.Our data demonstrate an unexpected role of Atg5 and shed new light on late endosome and lysosome biogenesis.

Membrane Trafficking in Plant Immunity

Plants employ sophisticated mechanisms to interact with pathogenic as well as beneficial microbes. Of those, membrane trafficking is key in establishing a rapid and precise response. Upon interaction with pathogenic microbes, surface-localized immune receptors undergo endocytosis for signal transduction and activity regulation while cell wall components, antimicrobial compounds, and defense proteins are delivered to pathogen invasion sites through polarized secretion. To sustain mutualistic associations, host cells also reprogram the membrane trafficking system to accommodate invasive structures of symbi- otic microbes. Here, we provide an analysis of recent advances in understanding the roles of secretory and endocytic membrane trafficking pathways in plant immune activation. We also discuss strategies deployed by adapted microbes to manipulate these pathways to subvert or inhibit plant defense.

TMEM43-S358L mutation enhances NF-κBTGFp signal cascade in arrhythmogenic right ventricular dysplasia/cardiomyopathy

Arrhythmogenic right ventricular dysplasia/cardiomyopathy(ARVD/C)is a genetic cardiac muscle disease that accounts for approximately 30%sudden cardiac death in young adults.The Ser358Leu mutation of transmembrane protein 43(TMEM43)was commonly identified in the patients of highly lethal and fully penetrant ARVD subtype,ARVD5.Here,we generated TMEM43 S358L mouse to explore the underlying mechanism.This mouse strain showed the classic patholo.gies of ARVD patients,including structural abnormalities and cardiac fibrofatty.TMEM43 S358L mutation led to hyper-activated nuclear factor kB(NFkB)activation in heart tissues and primary cardiomy.ocyte cells.Importantly,this hyper activation of NF-κB directly drove the expression of pro-fibrotic gene,transforming growth factor beta(TGFβ),and enhanced downstream signal,indicating that TMEM43 S358L mutation up-regulates NF-κB-TGFβ signal cascade during ARVD cardiac fibrosis.Our study partially reveals the regulatory mechanism of ARVD development.

FAK-targeting PROTAC as a chemical tool for the investigation of non-enzymatic FAK function in mice

Dear Editor,Animal models,most commonly mice,that lack a protein of interest play an important role in phenotypic and functional studies of a target gene,allowing researchers to answer various biological questions(Chaible et al,2010).At pre-sent,a variety of tools act at the DNA or RNA level to enable researchers to model gene function(and thus protein)deficiency,including nucleic acid based RNA interference(EI-bashir et al.,2001),antisense oligonucleotides(Schoch and Miller,2017),and genome editing-based CRISPR-Cas9(Doudna and Charpentier,2014)strategies.However,challenges remain.