Analysis of the expression profile of miRNAs related to skin photoaging in the GEO database

Background:Skin aging has recently gained significant attention in both society and skin care research.Understanding the biological processes of photoaging caused by long-term skin exposure to ultraviolet radiation is critical for preventing and treating skin aging.Therefore,it is important to identify genes related to skin photoaging and shed light on their functions.Methods:We used data from the Gene Expression Omnibus(GEO)database and conducted bioinformatics analyses to screen and extract microRNAs(miRNAs)and their downstream target genes related to skin photoaging,and to determine possible biological mechanisms of skin photoaging.Results:A total of 34 differentially expressed miRNAs and their downstream target genes potentially related to the biological process of skin photoaging were identified.Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that these target genes were enriched in pathways related to human papillomavirus infection,extracellular matrix(ECM)-receptor signaling,estrogen receptor,skin development,epidermal development,epidermal cell differentiation,keratinocyte differentiation,structural components of the ECM,structural components of the skin epidermis,and others.Conclusion:Based on the GEO database-derived findings,we determined that target genes of two miRNAs,namely miR-4667-5P-KRT79 and miR-139-5P-FOS,play an important role in skin photoaging.These observations could provide theoretical support and guidance for further research on skin aging-related biological processes.

Effects of copper mining on heavy metal contamination in a rice agrosystem in the Xiaojiang River Basin, southwest China

Metallic ore mining causes heavy metal pollution worldwide.However,the fate of heavy metals in agrosystems with long-term contamination has been poorly studied.Dongchuan District(Yunnan,southwest China),located at the middle reaches of the Xiaojiang River,is a well-known 2000-year-old copper mining site.In this work,a survey on soil heavy metal contents was conducted using a handheld X-ray fluorescence instrument to understand the general contamination of heavy metals in the Xiaojiang River Basin.Furthermore,river water,soil,and rice samples at six sites along the fluvial/alluvial fans of the river were collected and analyzed to implement an environmental assessment and an evaluation of irrigated agrosystem.V,Zn,and Cu soil levels(1724,1047,and 696mg·kg-1,respectively)far exceeded background levels.The geo-accumulation indexes(Igeo)showed that cultivated soils near the mining sites were polluted by Cd and Cu,followed by Zn,V,Pb,Cr,Ni,and U.The pollution index(Pi)indicated that rice in the area was heavily polluted with Pb,Cr,Cd,Ni,Zn,and Cu.The difference in orders of metal concentrations between the soil and rice heavy metal contamination was related to the proportion of bioavailable heavy metals in the soil.The crop consumption risk assessment showed that the hazard quotient exceeded the safe threshold,indicating a potential carcinogenic risk to consumers.The Nemerow integrated pollution index and health index indicated that the middle of the river(near the mining area)was the heaviest polluted site.

A cohort study of adolescents with depression in China:tracking multidimensional outcomes and early biomarkers for intervention

Background Depression in adolescents is recognised as a global public health concern,but little is known about the trajectory of its clinical symptoms and pathogenesis.Understanding the nature of adolescents with depression and identifying earlybiomarkers can facilitatepersonalised intervention andreducediseaseburden.Aims To track multidimensional outcomes of adolescents with depression and develop objective biomarkers for diagnosis,as well as response to treatment,prognosis and guidance for early identification and intervention.Methods This is a multidimensional cohort study on the Symptomatic trajectory and Biomarkers of Early Adolescent Depression(sBEAD).We planned to recruit more than 1000 adolescents with depression and 300 healthy controls within 5 years.Multidimensional clinical presentations and objective indicators are collected at baseline,weeks 4,8,12 and 24,and years 1,2,3,4 and 5.Conclusions To the best of our knowledge,this is the first longitudinal cohort study that examines multidimensional clinical manifestations and multilevel objective markers in Chinese adolescents with depression.This study aims at providing early individualised interventions for young,depressed patients to reduce the burden of disease.

Simulations of scattered neutrons for the time-of-flight enhanced diagnostics(TOFED)neutron spectrometer on EAST

The time-of-flight enhanced diagnostics(TOFED)neutron spectrometer has been installed in TOFED house,which is a newly-built neutron diagnostic lab outside the EAST experimental hall.The line of sight(LOS)of TOFED is defined by the collimator going through the 150 cm biological shielding wall,which can reduce background neutrons very effectively for the neutron spectral measurements.The Monte Carlo code MCNP5 is used in the simulations to characterize collimation effects and the radiation safety of the new house.The collimator makes neutron flux almost fully perpendicular to S 1 detectors.In addition,the proportion of scattered neutrons in the LOS of the TOFED is obtained for the measured spectral data interpretation.The simulation results show that the TOFED house satisfies the requirement for the TOFED operations at EAST and gives a safe environment for personnel access during the EAST operation.

Study of the relationship between sphenoid sinus volume and protrusions in the sphenoid sinus

The relationship between the volume of sphenoid sinus (SS) and the prevalence of internal carotid artery (ICA) and optic nerve (ON) protrusions in the SS was studied by using high-resolution CT imaging. The ICA and ON protrusions in SS were observed in randomly selected normal head CT scanning images from 350 adult subjects. Ac-cording to the incidence of ICA protrusion, three groups were divided into no ICA protrusion (70.75%), unilateral protrusion (8.68%) and bi-lateral protrusions (20.57%). The ON protrusion accounted for 16% in 350 subjects and accom-panied absolutely with ICA protrusion, but ICA protrusion appeared without accompanying with ON protrusion. The SS volume depended upon the protrusions in it and showed statistical dif-ferences, without ICA protrusion, the smallest size (11.16 ± 1.60) cm3;the unilateral protrusion, medium size (14.20 ± 1.80) cm3 and the bilateral protrusion, the largest size (25.03 ± 2.21) cm3. By observing 3D reconstructed models of ON and SS, we found ON was adjacent to SS (46%) and to posterior ethmoid sinuses (44%). The current study indicates that SS volume is varied with numbers of the protrusions and that ON location varies with the pneumatization of SS. Our results provide an anatomical basis to the surgeries for SS and its surrounding structures.

Eat at the right time: Regulation of ER-phagy receptors in plant response to environmental stresses

The endoplasmic reticulum(ER)is a cellular factory for biosynthesis of proteins and lipids.To accommodate a wide array of biosynthetic demands in responses to environmental stresses,the plant ER remodels to maintain a structural and functional homeostasis.A key process facilitating this balance is selective autophagy of the ER(ER-phagy),where malfunctioned ER is recognized,engulfed by autophagosomes,and then delivered to the vacuole for degradation.

Proximity-enabled covalent binding of IL-2 to IL-2Rα selectively activates regulatory T cells and suppresses autoimmunity

Interleukin-2(IL-2)is a pleiotropic cytokine that orchestrates bidirectional immune responses via regulatory T cells(Tregs)and effector cells,leading to paradoxical consequences.Here,we report a strategy that exploited genetic code expansion-guided incorporation of the latent bioreactive artificial amino acid fluorosulfate-L-tyrosine(FSY)into IL-2 for proximity-enabled covalent binding to IL-2Rαto selectively promote Treg activation.We found that FSY-bearing IL-2 variants,such as L72-FSY,covalently bound to IL-2Rαvia sulfur-fluoride exchange when in proximity,resulting in persistent recycling of IL-2 and selectively promoting the expansion of Tregs but not effector cells.Further assessment of L72-FSY-expanded Tregs demonstrated that L72-FSY maintained Tregs in a central memory phenotype without driving terminal differentiation,as demonstrated by simultaneously attenuated expression of lymphocyte activation gene-3(LAG-3)and enhanced expression of programmed cell death protein-1(PD-1).Subcutaneous administration of L72-FSY in murine models of pristane-induced lupus and graft-versus-host disease(GvHD)resulted in enhanced and sustained therapeutic efficacy compared with wild-type IL-2 treatment.The efficacy of L72-FSY was further improved by N-terminal PEGylation,which increased its circulatory retention for preferential and sustained effects.This proximity-enabled covalent binding strategy may accelerate the development of pleiotropic cytokines as a new class of immunomodulatory therapies.

面向工业废水处理的催化电极及燃料电池耦合体系

随着我国工业化水平的提高,工业废水的高效节能处理成为废水资源化与能源化进程中的重点和难点.工业废水中常含有难降解或有毒的有机污染物,水质复杂、可生化性差,采用传统废水处理技术(生物法、物化法等)难以实现高效处理和达标排放,残留毒物排入水体带来环境生态风险.电化学技术借助电场作用产生强氧化性物质,氧化去除难降解有机污染物,但去除效率较低、能耗及运行成本较高,限制了其在实际废水处理中的应用.高活性催化电极在结构、形貌、组成的优化进展,为构建以难降解污染物为燃料的新型燃料电池及废水处理体系提供了新的可能.本文围绕催化电极及燃料电池废水处理体系,综述了新型电极材料的制备、优化,探讨了基底、活性成分及其负载方式对催化电极和体系性能的影响;归纳了基于光催化燃料电池和微生物燃料电池的污染物催化降解及实际或模拟废水处理体系的研究进展,并对该类耦合体系的规模化应用作了展望.新型催化电极的开发和耦合燃料电池体系的优化设计,有望推动该技术在高效、节能实际(工业)废水处理中的应用.

High-Temperature Creep Behavior and Microstructural Evolution of a Cu-Nb Co-Alloyed Ferritic Heat-Resistant Stainless Steel

The creep behavior of Fe–17 Cr–1.2 Cu–0.5 Nb–0.01 C ferritic heat-resistant stainless steel was investigated at temperatures ranging from 973 to 1123 K and stresses from 15 to 90 MPa.The evolution of precipitates after creep deformation was analyzed by scanning electron microscopy,energy dispersion spectrum,and transmission electron microscopy.The minimum creep rate decreased with the decrease in the applied load and temperature,thereby extending the rupture life.Cu-rich phase and Nb-rich Laves particles were generated in dominant quantities during the creep process,and the co-growth relationship between them could be detected.Creep rupture was featured by ductile fracture with considerable necking.As increasing the temperature and decreasing the stress,the softening of the metal matrix was accelerated,showing more obvious plastic fl ow.The true stress exponent and activation energy were 4.9 and 375.5 kJ/mol,respectively,indicating that the creep deformation was dominated by the diffusion-controlled dislocation creep mechanism involving precipitate-dislocation interactions.Based on the creep rupture data obtained,the Monkman–Grant relation and Larson-Miller parameter were established,which described the creep rupture life for the studied steel well.

Proteins in DNA methylation and their role in neural stem cell proliferation and differentiation

Background:Epigenetic modifications,namely non-coding RNAs,DNA methylation,and histone modifications such as methylation,phosphorylation,acetylation,ubiquitylation,and sumoylation play a significant role in brain development.DNA methyltransferases,methyl-CpG binding proteins,and ten-eleven translocation proteins facilitate the maintenance,interpretation,and removal of DNA methylation,respectively.Different forms of methylation,including 5-methylcytosine,5-hydroxymethylcytosine,and other oxidized forms,have been detected by recently developed sequencing technologies.Emerging evidence suggests that the diversity of DNA methylation patterns in the brain plays a key role in fine-tuning and coordinating gene expression in the development,plasticity,and disorders of the mammalian central nervous system.Neural stem cells(NSCs),originating from the neuroepithelium,generate neurons and glial cells in the central nervous system and contribute to brain plasticity in the adult mammalian brain.Main body:Here,we summarized recent research in proteins responsible for the establishment,maintenance,interpretation,and removal of DNA methylation and those involved in the regulation of the proliferation and differentiation of NSCs.In addition,we discussed the interactions of chemicals with epigenetic pathways to regulate NSCs as well as the connections between proteins involved in DNA methylation and human diseases.Conclusion:Understanding the interplay between DNA methylation and NSCs in a broad biological context can facilitate the related studies and reduce potential misunderstanding.

Positive feedback between retinoic acid and 2-phospho-L-ascorbic acid trisodium salt during somatic cell reprogramming

Retinoic acid(RA)and 2-phospho-L-ascorbic acid trisodium salt(AscPNa)promote the reprogramming of mouse embryonic fibroblasts to induced pluripotent stem cells.In the current studies,the lower abilities of RA and AscPNa to promote reprogramming in the presence of each other suggested that they may share downstream pathways at least partially.The hypothesis was further supported by the RNA-seq analysis which demonstrated a high-level overlap between RA-activated and AscPNa activated genes during reprogramming.In addition,RA upregulated Glut1/3,facilitated the membrane transportation of dehydroascorbic acid,the oxidized form of L-ascorbic acid,and subsequently maintained intracellular L-ascorbic acid at higher level and for longer time.On the other hand,AscPNa facilitated the mesenchymal-epithelial transition during reprogramming,downregulated key mesenchymal transcriptional factors like Zeb1 and Twist1,subsequently suppressed the expression of Cyp26a1/b1 which mediates the metabolism of RA,and sustained the intracellular level of RA.Furthermore,the different abilities of RA and AscPNa to induce mesenchymal-epithelial transition,pluripotency,and neuronal differentiation explain their complex contribution to reprogramming when used individually or in combination.Therefore,the current studies identified a positive feedback between RA and AscPNa,or possibility between vitamin A and C,and further explored their contributions to reprogramming.

Exosomes released by melanocytes modulate fibroblasts to promote keloid formation: a pilot study

Keloids are a common type of pathological scar as a result of skin healing,which are extremely difficult to prevent and treat without recurrence.The pathological mechanism of keloids is the excessive proliferation of fibroblasts,which synthesize more extracellular matrices(ECMs),including type I/III collagen(COL-1/3),mucopolysaccharides,connective tissue growth factor(CTGF),also known as cellular communication network factor 2(CCN2),and fibronectin(FN)in scar tissue,mostly through the abnormal activation of transforming growth factor-β(TGF-β)/Smads pathway(Finnson et al.,2013;Song et al.,2018).

FGF7 enhances the expression of ACE2 in human islet organoids aggravating SARS-CoV-2 infection

The angiotensin-converting enzyme 2(ACE2)is a primary cell surface viral binding receptor for SARS-CoV-2,so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against COVID-19.In the current study,we utilized islet organoids derived from human embryonic stem cells(hESCs),animal models and COVID-19 patients to discover that fibroblast growth factor 7(FGF7)enhances ACE2 expression within the islets,facilitating SARS-CoV-2 infection and resulting in impaired insulin secretion.Using hESC-derived islet organoids,we demonstrated that FGF7 interacts with FGF receptor 2(FGFR2)and FGFR1 to upregulate ACE2 expression predominantly inβcells.This upregulation increases both insulin secretion and susceptibility ofβcells to SARS-CoV-2 infection.Inhibiting FGFR counteracts the FGF7-induced ACE2 upregulation,subsequently reducing viral infection and replication in the islets.Furthermore,retrospective clinical data revealed that diabetic patients with severe COVID-19 symptoms exhibited elevated serum FGF7 levels compared to those with mild symptoms.Finally,animal experiments indicated that SARS-CoV-2 infection increased pancreatic FGF7 levels,resulting in a reduction of insulin concentrations in situ.Taken together,our research offers a potential regulatory strategy for ACE2 by controlling FGF7,thereby protecting islets from SARS-CoV-2 infection and preventing the progression of diabetes in the context of COVID-19.