High-throughput calculations combining machine learning to investigate the corrosion properties of binary Mg alloys

Magnesium(Mg)alloys have shown great prospects as both structural and biomedical materials,while poor corrosion resistance limits their further application.In this work,to avoid the time-consuming and laborious experiment trial,a high-throughput computational strategy based on first-principles calculations is designed for screening corrosion-resistant binary Mg alloy with intermetallics,from both the thermodynamic and kinetic perspectives.The stable binary Mg intermetallics with low equilibrium potential difference with respect to the Mg matrix are firstly identified.Then,the hydrogen adsorption energies on the surfaces of these Mg intermetallics are calculated,and the corrosion exchange current density is further calculated by a hydrogen evolution reaction(HER)kinetic model.Several intermetallics,e.g.Y_(3)Mg,Y_(2)Mg and La_(5)Mg,are identified to be promising intermetallics which might effectively hinder the cathodic HER.Furthermore,machine learning(ML)models are developed to predict Mg intermetallics with proper hydrogen adsorption energy employing work function(W_(f))and weighted first ionization energy(WFIE).The generalization of the ML models is tested on five new binary Mg intermetallics with the average root mean square error(RMSE)of 0.11 eV.This study not only predicts some promising binary Mg intermetallics which may suppress the galvanic corrosion,but also provides a high-throughput screening strategy and ML models for the design of corrosion-resistant alloy,which can be extended to ternary Mg alloys or other alloy systems.

Milling degree affects the fermentation properties of rice:perspectives from the composition of nutrients and gut microbiota via in vitro fermentation

Fermentation substrates of rice with different milling degrees(MDs) were prepared and fermented with human feces to compare their fermentation properties and effects on gut microbiota.MD 0s,MD 5s and MD 60s represented brown rice,moderately-milled rice and white rice,respectively.After in vitro fermentation,the MD 5s group showed higher starch utilization,compared with the MD 0s and 60s groups evaluated by Fourier transform infrared spectrometer,and confocal laser scanning microscope.Effects of fermentation substrates of rice with different MDs on gut microbiota were evaluated by 16S rDNA sequencing.All the sample groups reduced the pH and produced short-chain fatty acids(SCFAs) and branched-chain fatty acids.The MD 5s group exhibited higher α-diversity than the MD 0s and 60s groups.Abundances of Phascolarctobacterium,Blautia and norank_f_Ruminococcaceae were higher in the MD 0s and 5s groups,compared with the MD 60s group.These bacteria were also positively correlated with the SCFAs production via Spearman correlation analysis.In vitro culture assay revealed that fermentation substrates of MD 0s and 5s promoted the growth of two probiotics(Akkermansia muciniphila and Bifidobacterium adolescentis).Our results showed that moderate milling might be an appropriate way to produce rice products with richer nutrients and better fermentation properties.

A highly degradable Mg-Al-Ca alloy with superior anti-tumor efficacy

Molecule hydrogen(H_(2)) has been used to suppress tumor growth. To employ the H_(2) therapy, it is necessary to use a proper agent for continuous generation of H_(2). As a biodegradable metal, magnesium(Mg) generates H_(2) in an aqueous environment, but the H_(2) release rate is still too low. Here, we design a Mg-Al-Ca(AX) alloy that degrades very rapidly due to the presence of a secondary phase Al_(2)Ca. Having a reduction potential much higher than Mg and any other Mg-based secondary phases, Al_(2)Ca accelerates the corrosion of the Mg matrix by a micro-galvanic process. Al_(2)Ca also enhances the strength and ductility of the AX alloy. AX alloy rods show better anti-tumor efficacy than pure Mg rods in vivo. Moreover, implanted AX alloy rods can be heated under an alternating magnetic field to suppress large-size tumors.This work suggests that the H_(2) therapy using highly degradable Mg alloys may provide an effective cancer treatment.

Tumor cell membrane-coated continuous electrochemical sensor for GLUT1 inhibitor screening

Glucose transporter 1(GLUT1)overexpression in tumor cells is a potential target for drug therapy,but few studies have reported screening GLUT1 inhibitors from natural or synthetic compounds.With current analysis techniques,it is difficult to accurately monitor the GLUT1 inhibitory effect of drug molecules in real-time.We developed a cell membrane-based glucose sensor(CMGS)that integrated a hydrogel electrode with tumor cell membranes to monitor GLUT1 transmembrane transport and screen for GLUT1 inhibitors in traditional Chinese medicines(TCMs).CMGS is compatible with cell membranes of various origins,including different types of tumors and cell lines with GLUT1 expression knocked down by small interfering RNA or small molecules.Based on CMGS continuous monitoring technique,we investigated the glucose transport kinetics of cell membranes with varying levels of GLUT1 expression.We used CMGS to determine the GLUT1-inhibitory effects of drug monomers with similar structures from Scutellaria baicalensis and catechins families.Results were consistent with those of the cellular glucose uptake test and molecular-docking simulation.CMGS could accurately screen drug molecules in TCMs that inhibit GLUT1,providing a new strategy for studying transmembrane protein-receptor interactions.

FGF-21、MIP-2在特发性肺纤维化中的变化及临床意义

目的研究成纤维细胞生长因子21(FGF-21)、巨噬细胞炎性蛋白2(MIP-2)在特发性肺纤维化中的变化及其临床意义。方法选取2013年12月-2018年12月海南省人民医院确诊的特发性肺纤维化患者80例,取患者肺纤维化组织为研究对象,取肺旁正常组织作为对照,Western blotting检测FGF-21和MIP-2蛋白的相对表达量,逆转录聚合酶链反应(RT-PCR)检测FGF-21 mRNA和MIP-2 mRNA的表达水平。比较两组FGF-21和MIP-2蛋白和mRNA的表达水平及其与临床病理特征的关系。利用条件Logistic回归分析特发性肺纤维化的相关因素,利用Cox回归分析特发性肺纤维化患者临床预后的相关因素。结果特发性肺纤维化组织FGF-21mRNA、MIP-2 mRNA及其蛋白的表达均较正常组织升高(P<0.05);FGF-21 mRNA和MIP-2 mRNA的表达与患者年龄、性别、吸烟、BMI和病程无关(P>0.05)。条件Logistic回归分析模型结果表明,特发性肺纤维化的发生与FGF-21 mRNA、MIP-2 mRNA呈正相关(P<0.05);Cox回归分析结果显示,FGF-21 mRNA、MIP-2 mRNA的高表达是影响特发性肺纤维化患者临床预后的独立危险因素。结论 FGF-21 mRNA、MIP-2 mRNA的高表达是特发性肺纤维化发生的相关因素,并与临床预后相关。

中西医结合分子配伍治疗肿瘤协同增效及逆转耐药的研究进展

增效减毒是中西医结合治疗肿瘤的特色和优势,如何有效增强抗肿瘤药物的敏感性或逆转其耐药性已成为当今肿瘤治疗亟待解决的问题。传统中医药主要通过发挥多组分、多靶点、多阶段的优势而具有增强抗肿瘤药物敏感性或逆转肿瘤耐药的功效,但其成分复杂,具体机制尚未明确。现代医学克服肿瘤耐药的主要策略为更换新一代药物,但这些药物靶点相对单一、不良反应较多,且容易诱发多药耐药,因而限制了其在肿瘤治疗中的广泛应用。本课题组在传统中医药配伍理论“君臣佐使”“七情和合”的基础上,研究了具有化疗增敏和逆转耐药作用的中药,挖掘出其发挥药效的有效成分,阐明了其发挥作用的分子机理,进一步将成分、结构、药效、机理清楚的多个活性分子与抗肿瘤药物优化配伍,组成新的“分子配伍”复方,形成药效叠加、不良反应减小的“分子配伍”药物,为增强抗肿瘤药物的疗效提供了一种中西医结合“分子配伍”的治疗策略。本文将系统性阐述中西医结合“分子配伍”的科学内涵,分析其在治疗肿瘤协同增效和抑制耐药方面的研究现状,以期为肿瘤治疗提供一种新的方法和策略。

Geometric Mean Decomposition Based Hybrid Precoding for Millimeter-Wave Massive MIMO

Hybrid precoding can reduce the number of required radio frequency(RF)chains in millimeter-Wave(mmWave) massive MIMO systems. However, existing hybrid precoding based on singular value decomposition(SVD) requires the complicated bit allocation to match the different signal-to-noise-ratios(SNRs) of different sub-channels. In this paper,we propose a geometric mean decomposition(GMD)-based hybrid precoding to avoid the complicated bit allocation. Specifically,we seek a pair of analog and digital precoders sufficiently close to the unconstrained fully digital GMD precoder. To achieve this, we fix the analog precoder to design the digital precoder, and vice versa. The analog precoder is designed based on the orthogonal matching pursuit(OMP) algorithm, while GMD is used to obtain the digital precoder. Simulations show that the proposed GMD-based hybrid precoding achieves better performance than the conventional SVD-based hybrid precoding with only a slight increase in complexity.

中西医整合理念在肝癌诊治中的应用

随着肿瘤学科分支越来越细,其不足之处也逐渐显现.现代医学思维模式下,肝癌(hepatocellular carcinoma, HCC)的诊治也存在着过于细化,碎片化的趋势,这导致HCC诊治缺乏整体观.随着医学的发展,临床对HCC的治疗越来越强调个体化、整体化及整合理念的应用.本文从当今整合医学角度出发,把HCC的诊治过程视为一个有机的、具有中西医整合特征的全身性疾病,提出单纯消灭癌灶不等于治愈了HCC.同时指出,在临床实践中需要有机地运用基础临床整合、医学药学整合、中医西医整合、局部整体整合的思路对HCC进行重新的再认识,以期发现HCC诊治的新方法,新思路,建立新的HCC整合治疗医学观.

Preparation, characterization, pharmacokinetics and anticancer effects of PEGylated β-elemene liposomes

Objective:This study aimed to develop a new polyethylene glycol(PEG)ylatedβ-elemene liposome(PEG-Lipo-β-E)and evaluate its characterization,pharmacokinetics,antitumor effects and safety in vitro and in vivo.Methods:The liposomes were prepared by ethanol injection and high-pressure micro-jet homogenization.Characterization of the liposomes was conducted,and drug content,entrapment efficiency(EE),in vitro release and stability were studied by ultra-fast liquid chromatography(UFLC)and a liquid surface method.Blood was drawn from rats to establish the pharmacokinetic parameters.The anticancer effect was evaluated in a KU-19-19 bladder cancer xenograft model.Histological analyses were performed to evaluate safety.Results:The PEG-Lipo-β-E showed good stability and was characterized as 83.31±0.181 nm in size,0.279±0.004 in polydispersity index(PDI),-21.4±1.06 mV in zeta potential,6.65±0.02 in pH,5.024±0.107 mg/mL inβ-elemene(β-E)content,and 95.53±1.712%in average EE.The Fourier transform infrared spectroscopy(FTIR)and differential scanning calorimetry(DSC)indicated the formation of PEG-Lipo-β-E.Compared to elemene injection,PEG-Lipo-β-E demonstrated a 1.75-fold decrease in clearance,a 1.62-fold increase in half-life,and a 1.76-fold increase in area under the concentration-time curves(AUCs)from 0 hour to 1.5 hours(P<0.05).PEG-Lipo-β-E also showed an enhanced anticancer effect in vivo.Histological analyses showed that there was no evidence of toxicity to the heart,kidney,liver,lung or spleen.Conclusions:The present study demonstrates PEG-Lipo-β-E as a new formulation with ease of preparation,high EE,good stability,improved bioavailability and antitumor effects.

An ATF24 peptide-functionalized β-elemene-nanostructured lipid carrier combined with cisplatin for bladder cancer treatment

Objective:In this study,we aimed to develop an amino-terminal fragment(ATF)peptide-targeted liposome carryingβ-elemene(ATF24-PEG-Lipo-β-E)for targeted delivery into urokinase plasminogen activator receptor-overexpressing bladder cancer cells combined with cisplatin(DDP)for bladder cancer treatment.Methods:The liposomes were prepared by ethanol injection and high-pressure microjet homogenization.The liposomes were characterized,and the drug content,entrapment efficiency,andin vitro release were studied.The targeting efficiency was investigated using confocal microscopy,ultra-fast liquid chromatography,and an orthotopic bladder cancer model.The effects of ATF24-PEG-Lipo-β-E combined with DDP on cell viability and proliferation were evaluated by a Cell Counting Kit-8(CCK-8)assay,a colony formation assay,and cell apoptosis and cell cycle analyses.The anticancer effects were evaluated in a KU-19-19 bladder cancer xenograft model.Results:ATF24-PEG-Lipo-β-E had small and uniform sizes(~79 nm),high drug loading capacity(~5.24 mg/mL),high entrapment efficiency(98.37±0.95%),and exhibited sustained drug release behavior.ATF24-PEG-Lipo-β-E had better targeting efficiency and higher cytotoxicity than polyethylene glycol(PEG)ylatedβ-elemene liposomes(PEG-Lipo-β-E).DDP,combined with ATF24-PEG-Lipo-β-E,exerted a synergistic effect on cellular apoptosis and cell arrest at the G2/M phase,and these effects were dependent on the caspase-dependent pathway and Cdc25C/Cdc2/cyclin B1 pathways.Furthermore,thein vivo antitumor activity showed that the targeted liposomes effectively inhibited the growth of tumors,using the combined strategy.Conclusions:The present study provided an effective strategy for the targeted delivery ofβ-elemene(β-E)to bladder cancer,and a combined strategy for bladder cancer treatment.

X-ray repair cross-complementing group 1 polymorphisms and hepatocellular carcinoma:A meta-analysis

AIM： To perform a systematic meta-analysis to in- vestigate the association between X-ray repair crosscomplementing group 1 （XRCC1） polymorphisms and hepatocellular carcinoma （HCC） risk. METHODS： Relevant studies extracted from PubMed, Embase, Wanfang, VIP and the Chinese National Knowledge Infrastructure databases up to March 2012 were included in the study. Stata software, version 11.0, was used for the statistical analysis. The odds ratios （ORs） and 95% confidence interval （CI） of the XRCC1 polymorphisms in HCC patients were analyzed and compared with healthy controls. The meta-analysis was performed using fixed-effect or random-effect methods, depending on the absence or presence of significant heterogeneity. RESULTS： Eleven studies with 2075 HCC cases and 2604 controls met our eligibility criteria （four studies, 888 cases and 938 controls for Arg194Trp, four studies, 858 cases and 880 controls for Arg280His, and nine studies, 1845 cases and 2401 controls for Arg399Gln）. The meta-analysis revealed no associations between the Arg194Trp and Arg399GIn polymorphisms of the XRCC1 gene and HCC risk under all contrast models （codominant, dominant and recessive models） in the overall analysis and sensitivity analysis （the studies with controls not in the Hardy-Weinberg equilibrium were excluded）. For XRCC1 Arg280His polymorphism, the overall analysis revealed the significant associa- tion between the His/His genotype and the increased risk of HCC （His/His vs Arg/Arg model, OR： 1.96, 95% CI： 1.03-3.75, P = 0.04）. However, sensitivity analysis showed an altered pattern of result and non-significant association （OR： 2.06, 95% CI： 0.67-6.25, P = 0.20）. The heterogeneity hypothesis test did not reveal any heterogeneity, and Begg＇s and Egger＇s tests did not find any obvious publication bias. CONCLUSION： The XRCC1 Arg194Trp and Arg399GIn polymorphisms are not associated with HCC risk. More rigorous association studies are needed to verify the involvement ofXRCC1 Arg280His polymorphism in HCC susceptibility.

全基因组蛋白质的标签细胞和小鼠资源库建设

小鼠是最广泛使用的模式生物,构建基因改造的小鼠模型是研究基因功能和疾病发生机制的重要手段。从20世纪80年代发展至今,小鼠基因改造技术更新迭代,主要包括胚胎干细胞介导的同源重组策略、配子介导的转基因策略、以及最新基于CRISPR/Cas9技术的遗传改造策略等。由我国科学家自主研发的全新小鼠基因改造技术——“人造精子细胞”(或“类精子干细胞”)介导的半克隆技术与以往策略相比,具有小鼠构建周期短、效率高、成本低、应用场景兼容性强等特点。为了摆脱我国小鼠实验动物“卡脖子”风险,填补标签蛋白质小鼠资源库的国际空白,中国科学院分子细胞科学卓越创新中心进行了战略资源布局,于2017年启动了基因组标签计划(genome tagging project,GTP),并成立了GTP研发中心致力于建立全新的标签细胞和小鼠战略资源库。GTP研发中心通过对“人造精子细胞”基因组上编码蛋白质的基因原位系统性地添加标签序列,建立了可用液氮保存的标签细胞资源库,并作为生产标签小鼠的种子贮备。当需要标签小鼠时,利用半克隆技术将标签细胞注射到小鼠卵子中,一步法获得标签小鼠。标签小鼠可通过标准化的标签抗体监测特定蛋白质从而实现蛋白质的在体、实时、动态研究。目前,GTP研发中心已构建1532个标签细胞和277个标签小鼠,初步形成了具有特色标签产品战略资源库;已有242个标签小鼠品系被分发到3个囯家15个地区的32个研究机构,供66个研究团队使用。同时,GTP研发中心已建立完备的标签产品信息,定期在GTP官网上发布更新,供科研人员查询、订购和定制。后续标签小鼠的配繁规律、标签蛋白质组织图谱描绘、发表文献等也会陆续更新到GTP官网。GTP研发中心将对标行业尖端,打造全球独特性战略资源,为蛋白质功能研究提供标准化平台,推动生命科学的发展和临床转化。

Clinical distribution and molecular profiling on postoperative colorectal cancer patients with different traditional Chinese medicine syndromes

Background:Traditional Chinese medicine(TCM)syndrome,also named syndrome,are comprehensive and integral analyses of clinical information which helps to guide different individualized treatment prescriptions.Methods:Thirty healthy controls and 80 colorectal cancer(CRC)patients(including 33 Spleen Qi Deficiency syndrome,23 Dampness Heat syndrome,17 Blood Stasis syndrome and 7 other syndrome)were enrolled into this study.Human mRNAs were extracted from peripheral blood mononuclear cells.The gene expression for CRC patients with different TCM syndrome was determined by microarray and qRT-PCR.Results:Spleen Qi Deficiency,Dampness Heat and Blood Stasis were the most common syndromes in CRC patients.There is a significant difference was found in mRNA expression levels(especially for PIK3CA,STAT3,SOX9 and KDM5C)among Spleen Qi Deficiency,Dampness Heat and Blood Stasis syndrome groups.The higher mRNA levels of JNK1,TP53,MLH1,MSH6,PMS2,SOCS3,TCF7L2,FAM123B,PSAP,FBXW7,SALL4 and the lower expression of inflammatory cytokine IL-6 were found in Spleen Qi Deficiency group but not other syndrome types.The higher mRNA levels of KRAS,MUC16,EGFR,GRASP65,PIK3CA,MAPK7,CD24,STAT3,SLC11A1,Bcl-2,TXNDC17 and some inflammatory cytokines(IL-6,IL-23,TNF-a,CXCR4)were found in Dampness Heat group but not other syndrome types.Blood Stasis syndrome showed higher expression of SOX9,MLH1,MSH6,KDM5C,PCDH11X,PSAP and SALL4,and lower mRNA levels of PIK3CA,CD24,STAT3,CXCR4,TXNDC17 and TP53.The CRC patients with Dampness Heat syndrome might have a poor prognosis than other syndrome types.Conclusion:The identification of syndrome conditions had different impacts on CRC prognosis,and which might be related with different mRNA expression levels.Some oncogenes and pro-inflammatory cytokines were highly expressed in Dampness Heat group but not other syndrome types,suggesting that the CRC patients with Dampness Heat syndrome might have a poor prognosis.Our results prelimitarily uncovered the molecular basis of syndrome differences in CRC prognosis,a better understanding for TCM treatment of CRC.

Efficacy of integrative medicine in deficiency of both qi and yin in the rat model of type 2 diabetes

Objective:To establish a rat model of type 2 diabetes(T2DM)manifesting the Chinese medicine syndrome pattern of both qi and yin deficiency for evaluating the efficacy of a Chinese herbal formula(CHF),integrative medicine(IM),and pioglitazone(PIO)on T2DM indicators in the animal model.Methods:The rat model was induced by a high-fat diet(HFD)and streptozotocin(STZ,30 mg/kg).CHF(3.4 g/kg),PIO(2.7 mg/kg),and IM(3.4 g CHF+2.7 mg PIO)were administered to rats once daily for 14 days.Related laboratory parameters were observed.Results:Diabetic rats showed unsmooth fur,alopecia,reduced activity,huddling,somnolence,depression,pale or reddened tongue,damp/dark red tail,and high levels of water and food intake,urine volume,and stool weight,but weakened grip strength.Low levels of serum SOD,Nat-Kt-ATPase,cAMP/cGMP,and a high level of iNOS were observed.Hyperglycemia,hyperinsulinemia,insulin resistance,high levels of serum glucagon/IDE and pancreatic amylin,and low serum and pancreatic SS levels were evident as well.Conclusions:A rat model of T2DM with both qi and yin deficiency was successfully replicated.CHF appeared to be more efficacious than IM and PIO in the rat model of qi and yin deficiency pattern of T2DM,though IM and PIO were each found to have their merits and drawbacks in attenuating T2DM indicators in the rat model.

Dramatic change of the self-diffusions of colloidal ellipsoids by hydrodynamic interactions in narrow channels

The self-diffusion problem of Brownian particles under the constraint of quasi-one-dimensional(q1 D) channel has raised wide concern.The hydrodynamic interaction(HI) plays an important role in many practical problems and two-body interactions remain dominant under q1D constraint.We measure the diffusion coefficient of individual ellipsoid when two ellipsoidal particles are close to each other by video-microscopy measurement.Meanwhile, we obtain the numerical simulation results of diffusion coefficient using finite element software.We find that the self-diffusion coefficient of the ellipsoid decreases exponentially with the decrease of their mutual distance X when X < X0, where X0 is the maximum distance of the ellipsoids to maintain their mutual influence, X0 and the variation rate are related to the aspect ratio p = a/b.The mean squared displacement(MSD) of the ellipsoids indicates that the self-diffusion appears as a crossover region, in which the diffusion coefficient increases as the time increases in the intermediate time regime, which is proven to be caused by the spatial variations affected by the hydrodynamic interactions.These findings indicate that hydrodynamic interaction can significantly affect the self-diffusion behavior of adjacent particles and has important implications to the research of microfluidic problems in blood vessels and bones, drug delivery, and lab-on-chip.

光控诱导重组系统的开发与应用

位点特异性重组系统由重组酶和特异性识别位点两部分组成,是一种强大的基因操作工具,被广泛运用于生命科学研究。已开发的诱导型重组系统以时空方式精准调控细胞和动物的基因表达,被用于基因功能研究、细胞谱系示踪和疾病治疗等领域。根据诱导重组酶时空表达方式的不同,诱导型重组系统可分为化学诱导和光控诱导两种方式。光控诱导重组系统是利用光作为诱导剂,根据光控方式和对象的不同,可进一步分为光笼和光遗传学两类。光笼诱导重组系统是利用光敏基团来控制化学诱导剂或重组酶,光诱导前它们的活性被光敏基团抑制;在特定光照射后,它们的活性被恢复,进而实现光控诱导基因重组。光遗传学诱导重组系统是通过光遗传学开关介导分割型重组酶的重新激活来诱导基因重组。其中光遗传学开关由一系列基因编码的光敏蛋白组成,包括隐花色素、VIVID蛋白、光敏色素等。这些类型丰富的光控诱导重组系统为从高时空分辨率的维度解析基因的表达和功能提供了更多的工具,以满足日益复杂的生命科学研究需求。本文主要对不同类型光控诱导重组系统的开发原理及应用进行综述,比较其优缺点,最后对未来开发更多光控重组系统进行展望,旨在为系统优化升级提供理论基础和指导。

Fabrication of CuO_x thin-film photocathodes by magnetron reactive sputtering for photoelectrochemical water reduction

The CuO_x thin film photocathodes were deposited on F-doped Sn O_2 (FTO)transparent conducting glasses by alternating current(AC)magnetron reactive sputtering under different Ar:O_2 ratios.The advantage of this deposited method is that it can deposit a CuO_x thin film uniformly and rapidly with large scale.From the photoelectrochemical(PEC)properties of these CuO_x photocathodes,it can be found that the CuO_x photocathode with Ar/O_2 30:7 provide a photocurrent density ofà3.2 m A cm^(à2)under a bias potentialà0.5 V(vs.Ag/Ag Cl),which was found to be twice higher than that of Ar/O_2 with 30:5.A detailed characterization on the structure,morphology and electrochemical properties of these CuO_x thin film photocathodes was carried out,and it is found that the improved PEC performance of CuO_x semiconductor photocathode with Ar/O_230:7 attributed to the less defects in it,indicating that this Ar/O_230:7 is an optimized condition for excellent CuO_x semiconductor photocathode fabrication.

心肌缺血再灌注损伤中心肌免疫细胞单细胞图谱绘制及具有心肌保护效应的Ym-1hi中性粒细胞的鉴定

Myocardial ischemia–reperfusion injury(MIRI)is a major hindrance to the success of cardiac reperfusion therapy.Although increased neutrophil infiltration is a hallmark of MIRI,the subtypes and alterations of neutrophils in this process remain unclear.Here,we performed single-cell sequencing of cardiac CD45^(+)cells isolated from the murine myocardium subjected to MIRI at six-time points.We identified diverse types of infiltrating immune cells and their dynamic changes during MIRI.Cardiac neutrophils showed the most immediate response and largest changes and featured with functionally heterogeneous subpopulations,including Ccl3^(hi)Neu and Ym-1^(hi)Neu,which were increased at 6 h and 1 d after reperfusion,respectively.Ym-1^(hi)Neu selectively expressed genes with protective effects and was,therefore,identified as a novel specific type of cardiac cell in the injured heart.Further analysis indicated that neutrophils and their subtypes orchestrated subsequent immune responses in the cardiac tissues,especially instructing the response of macrophages.The abundance of Ym-1^(hi)Neu was closely correlated with the therapeutic efficacy of MIRI when neutrophils were specifically targeted by anti-Lymphocyte antigen 6 complex locus G6D(Ly6G)or anti-Intercellular cell adhesion molecule-1(ICAM-1)neutralizing antibodies.In addition,a neutrophil subtype with the same phenotype as Ym-1^(hi)Neu was detected in clinical samples and correlated with prognosis.Ym-1 inhibition exacerbated myocardial injury,whereas Ym-1 supplementation significantly ameliorated injury in MIRI mice,which was attributed to the tilt of Ym-1 on the polarization of macrophages toward the repair phenotype in myocardial tissue.Overall,our findings reveal the antiinflammatory phenotype of Ym-1^(hi)Neu and highlight its critical role in myocardial protection during the early stages of MIRI.

The roles and mechanisms of SREBP1 in cancer development and drug response

Cancer occurrence and development are closely related to increased lipid produc-tion and glucose consumption.Lipids are the basic component of the cell membrane and play a significant role in cancer cell processes such as cell-to-cell recognition,signal transduction,and energy supply,which are vital for cancer cell rapid proliferation,invasion,and metastasis.Sterol regulatory element-binding transcription factor 1(SREBP1)is a key transcription factor regulating the expression of genes related to cholesterol biosynthesis,lipid homeostasis,and fatty acid synthesis.In addition,SREBP1 and its upstream or downstream target genes are implicated in various metabolic diseases,particularly cancer.However,no review of sREBP1 in cancer biology has yet been published.Herein,we summarized the roles and mechanisms of SREBP1 biological processes in cancer cells,including SREBP1 modification,lipid metabolism and reprogramming,glucose and mitochondrial metabolism,immunity,and tumor microenvi-ronment,epithelial-mesenchymal transition,cell cycle,apoptosis,and ferroptosis.Addition-ally,we discussed the potential role of SREBP1 in cancer prognosis,drug response such as drug sensitivity to chemotherapy and radiotherapy,and the potential drugs targeting SREBP1 and its corresponding pathway,elucidating the potential clinical application based on SREBP1 and its corresponding signal pathway.

Rumen metagenome reveals the mechanism of mitigation methane emissions by unsaturated fatty acid while maintaining the performance of dairy cows

Dietary fat content can reduce the methane production of dairy cows;however,the relevance fatty acid(FA)composition has towards this inhibitory effect is debatable.Furthermore,in-depth studies elucidating the effects of unsaturated fatty acids(UFA)on rumen function and the mechanism of reducing methane(CH4)production are lacking.This study exposed 10 Holstein cows with the same parity,similar milk yield to two total mixed rations:low unsaturated FA(LUFA)and high unsaturated FA(HUFA)with similar fat content.The LUFA group mainly added fat powder(C16:0>90%),and the HUFA group mainly replaced fat powder with extruded flaxseed.The experiment lasted 26 d,the last 5 d of which,gas exchange in respiratory chambers was conducted to measure gas emissions.We found that an increase in the UFA in diet did not affect milk production(P>0.05)and could align the profile of milk FAs more closely with modern human nutritional requirements.Furthermore,we found that increasing the UFA content in the diet lead to a decrease in the abundance of Methanobrevibacter in the rumen(|linear discriminant analysis[LDA]score|>2 and P 2 and P<0.05),which ultimately decreased CH4 production(P<0.05).Our results illustrated the mechanism involving decreased CH4 production when fed a UFA diet in dairy cows.We believe that our study provides new evidence to explore CH4 emission reduction measures for dairy cows.