Revolutionizing tumor immunotherapy:unleashing the power of progenitor exhausted T cells

In exploring persistent infections and malignancies, a distinctive subgroup of CD8^(+) T cells, progenitor exhausted CD8^(+) T(Tpex) cells, has been identified. These Tpex cells are notable for their remarkable self-renewal and rapid proliferation abilities. Recent strides in immunotherapy have demonstrated that Tpex cells expand and differentiate into responsive exhausted CD8^(+) T cells, thus underscoring their critical role in the immunotherapeutic retort. Clinical examinations have further clarified a robust positive correlation between the proportional abundance of Tpex cells and enhanced clinical prognosis. Tpex cells have found noteworthy applications in the formulation of inventive immunotherapeutic approaches against tumors. This review describes the functions of Tpex cells in the tumor milieu, particularly their potential utility in tumor immunotherapy. Precisely directing Tpex cells may be essential to achieving successful outcomes in immunotherapy against tumors.

Genetic variation in GmCRP contributes to nodulation in soybean(Glycine max Merr.)

Symbiosis between soybean and rhizobia contributes to soybean yield and quality. Although secreted rhizobial type Ⅲ effectors are known to regulate infection and promote nitrogen fixation, much about them remains unknown. Mutation of NopC, a type Ⅲ effector from Sinorhizobium fredii HH103, reduced nodule numbers and dry weights in 310 soybean accessions, and expression of NopC in soybean hairy roots promoted symbiosis. Based on observed differences in nodule traits between Suinong 14 and Zyd 00,006inoculated with HH103 and the NopC mutant, 11 QTL associated with rhizobia were identified in chromosome segment substitution lines(CSSLs) derived from Suinong 14 and Zyd 00006. Using chromosome fragment insertion, whole-genome sequencing of Suinong 14 and Zyd 00006, and qRT-PCR,Glyma.19G176300(GmCRP) was identified as a candidate gene associated with NopC, and GmCRP was found to be induced by NopC to positively regulate nodulation. SNPs located in the regulatory regions of GmCRP influenced its expression response to NopC, with SNPs contributing to nodulation having been selected during domestication. Our findings reveal the function of a soybean gene encoding a rhizobial type Ⅲ effector that contributes to symbiosis, and will facilitate the practical application of symbiotic nitrogen fixation in molecular breeding.

Single Nucleotide Polymorphisms (SNPs) of URAT1 (rs7932775) and ABCG2 (rs3825016) on Chronic Kidney Disease Patients with Hyperuricemia

Background: More and more chronic kidney disease (CKD) patients are accompanied with hyperuricaemia. As is known, hyperuricaemia is an independent hazard of both cardiovascular diseases (CVD) and chronic kidney diseases. We aim at identifying Single Nucleotide Polymorphism (SNP) difference of hURAT1 (rs7932775) and ABCG2 (rs3825016) on CKD patient with hyperuricemia and/or gout. Methods: All forty-two CKD patients were divided into two groups: hyperuricemia, and control group. 24 hours urine sample and serum were prepared for testing biochemistry parameters. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method is used to analyze hURAT1 and ABCG2 single nucleotide polymorphisms in different groups. Results: 17 patients have CT SNP of hURAT1 (rs7932775) and 13 patients have CT SNP of ABCG2 (rs3825016) in hyperuricemia group, while only 5 persons and 6 persons have the same mutations in control group respectively. 7 patients have CT SNP of both hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group, while only 2 persons have the same mutations in control group. CT mutation rates of hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group were 60.7% (17/28) and 50% (13/28) respectively, higher than that of control group (35.7% (5/14) and 42.8% (6/14)). What is more, Double SNP mutations in both hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group were 25% (7/28), higher than that of control group (14.2%, 2/14). Conclusion: There are higher mutation rates of CT SNP in hURAT1 (rs7932775) and/or ABCG2 (rs3825016) in hyperuricemia group. We can conclude that hyperuricemia is a high risk factor in progress of CKD, which is necessary to take measures of decreasing serum uric acid to delay CKD progress.

A soybean NAC homolog contributes to resistance to Phytophthora sojae mediated by dirigent proteins

Phytophthora sojae infection severely impairs soybean production. We previously identified a dirigent protein, Gm DRR1(Glycine max Disease Resistant Response 1), that increases soybean resistance to P.sojae. However, the molecular basis of Gm DRR1 function remained largely uncharacterized. In the present study, analysis of Gm DRR1-RNAi, Gm DRR1-overexpressing, and CRISPR/Cas9-derived Gmdrr1 mutant lines revealed that Gm DRR1 expression significantly restricted P. sojae growth. Combining coimmunoprecipitation with liquid chromatography–tandem mass spectrometry revealed a Gm DRR1-interacting protein, Gm DRR2, which is homologous to Gm DRR1. An E-coniferyl alcohol coupling assay indicated that Gm DRR1 promotes the synthesis of(+)-pinoresinol, which helps to protect plants from P. sojae. The Gm NAC1(Glyma.05 G025500) transcription factor bound to the Gm DRR1 promoter both in vitro and in vivo to upregulate Gm DRR1 expression. Soybean resistance to P. sojae was increased by overexpression of Gm NAC1. Our findings suggest a novel signaling pathway involving a NAC transcription factor that mediates soybean resistance to P. sojae. Specifically, Gm NAC1 directly induces Gm DRR1 expression to increase resistance of soybean plants to P. sojae.

高温环境作用下的压力容器检验与评估技术分析

压力容器在工业化发展中得到了广泛推广,且压力容器越来越能适应恶劣的生产环境,在高温环境作用下,压力容器仍然能够创造价值。但高温对压力容器的结构和材料会造成不可避免的磨损和破坏,压力容器自身受到的多重应力作用也容易导致压力容器发生变形、裂纹等缺陷。本文对高温环境作用下的压力容器检验与评估技术进行了分析,讨论高温环境下的压力容器如何优化无损超声检验技术,分析了应力分析、疲劳分析、缺陷分析在压力容器安全评估中的应用。

对钛合金高压容器的失效机制的分析

为确保钛合金压力容器失效机制分析的精准性,本次研究提出采用热力耦合模拟的方式进行失效机制检测,利用微观分析法和有限元软件模型分析法来对TC18钛合金压力容器进行承压检验。整个实验过程利用JR-3DSS光学扫描仪来确定钛合金高压容器表面情况,并利用相关公式计算容器性能。研究表明,造成钛合金高压容器断裂的主要原因为腐蚀和高压气体冲击容器的薄弱位置形成沟槽,在冲击荷载和腐蚀的相互作用凸显为断裂特征。

Microstructure evolution and mechanical anisotropy of M50 steel ball bearing rings during multi-stage hot forging

This study aimed to explore the evolution of flow lines and microstructures of M50-steel bearing ring and the anisotropy of its tensile mechanical properties after Multi-Stage Hot Forging(MSHF) and subsequent spheroidizing annealing(MSHFA). To this end, the present study mainly employed stereo microscopy, Optical Metallurgical Microscopy(OMM), Scanning Electron Microscopy(SEM), and Electron Backscatter Diffraction(EBSD) to characterize and analyze the workpiece at each processing stage of MSHF while performing microhardness measurement and uniaxial tensile experiment to test and analyze the mechanical properties of the workpiece. Macro-structure observation showed that the simulation results of flow lines at each stage were consistent with the experimental results. Microscopic observation showed that, after MSHF, deformation gradually became less significant along the outward radial direction of the bearing ring. After MSHFA,the microstructures of the bearing ring became uniform, whereas primary carbides did not dissolve.The mechanical properties were better in the axial direction(AD) than in the radial(RD) and circumferential directions(CD) after MSHF due to the smaller grain width. After MSHFA, the mechanical properties in the ADs and CDs were better than those in the RDs, which was due to the large cross-sectional area of carbides along the flow-line direction.

Associations of insulin resistance and beta-cell function with abnormal lipid profile in newly diagnosed diabetes

Background:Abnormal lipids are strong predictors of cardiovascular disease in type 1 diabetes mellitus(T1DM)and type 2 diabetes mellitus(T2DM).However,the potential associations of insulin resistance(IR)and beta-cell function(BCF)with abnormal lipids in newly diagnosed T1DM or T2DM patients are not fully understood.Methods:A cross-sectional survey of 15,928 participants was conducted.Homeostasis model assessment and postprandial C-peptide levels were used to estimate IR and BCF.A restricted cubic spline(RCS)nested in binary logistic regression was used to examine the associations of IR and BCF with abnormal lipids.Results:High triglyceride(TG),low high-density lipoprotein cholesterol,and high low-density lipoprotein cholesterol(LDL-C)accounted for 49.7%,47.8%,and 59.2%of the participants,respectively.In multivariable analysis,high IR was associated with an increased risk of high TGs(P for trend<0.001)in T1DM and is associated with an elevated risk of high TG and low HDL-C(all P for trend<0.01)in T2DM.Low BCF was not associated with risks of dyslipidemia in patients with T1DM or T2DM after adjustment for potential confounders.Conclusion:High IR had different associations with the risk of dyslipidemia in newly diagnosed T1DM and T2DM patients,suggesting that early treatment that improves IR may benefit abnormal lipid metabolism.

A loss-of-function mutant allele of a glycosyl hydrolase gene has been co-opted for seed weight control during soybean domestication

The resultant DNA from loss-of-function mutation can be recruited in biological evolution and development.Here,we present such a rare and potential case of“to gain by loss”as a neomorphic mutation during soybean domestication for increasing seed weight.Using a population derived from a chromosome segment substitution line of Glycine max(SN14)and Glycine soja(ZYD06),a quantitative trait locus(QTL)of 100-seed weight(q HSW)was mapped on chromosome 11,corresponding to a truncatedβ-1,3-glucosidase(βGlu)gene.The novel gene hsw results from a 14-bp deletion,causing a frameshift mutation and a premature stop codon in theβGlu.In contrast to HSW,the hsw completely lostβGlu activity and function but acquired a novel function to promote cell expansion,thus increasing seed weight.Overexpressing hsw instead of HSW produced large soybean seeds,and surprisingly,truncating hsw via gene editing further increased the seed size.We further found that the core 21-aa peptide of hsw and its variants acted as a promoter of seed size.Transcriptomic variation in these transgenic soybean lines substantiated the integration hsw into cell and seed size control.Moreover,the hsw allele underwent selection and expansion during soybean domestication and improvement.Our work cloned a likely domesticated QTL controlling soybean seed weight,revealed a novel genetic variation and mechanism in soybean domestication,and provided new insight into crop domestication and breeding,and plant evolution.

支架机械特征介导Yes相关蛋白信号调节干细胞生物行为的研究进展

干细胞可感知局部微环境理化特征,传递并转导机械或化学信号以调控黏附、增殖、分化、代谢和免疫等生物行为。组织工程常通过设计人工支架模拟体内微环境机械特征对干细胞进行仿生调控,研究发现从细胞感知外界机械刺激到启动生物行为发生变化的过程中,Yes相关蛋白(YAP)发挥了重要作用。本文旨在对支架机械特征的功能,及其介导YAP调控干细胞生物行为作用机制的研究进展进行综述。

中性粒细胞弹性蛋白酶基因突变相关周期性中性粒细胞减少症1例

现报道1例幼年起病的中性粒细胞弹性蛋白酶(ELANE)基因突变相关周期性中性粒细胞减少症(CN)的诊治过程。患者男性,24岁,表现为反复发热伴口腔黏膜溃疡,腹泻,中性粒细胞1.04×10^(9)/L。予痰热清静脉滴注20 ml/次、1次/d,联合口服阿奇霉素500 mg/次、1次/d,治疗7 d,患者体温维持在36.5℃左右。基因检测报告显示ELANE基因杂合突变,对其父母亦进行了基因检测,结果显示母亲ELANE基因存在相同突变,父亲正常,最终诊断CN。予粒细胞集落刺激因子(G-CSF)皮下注射2μg·kg^(-1)·d^(-1),3 d后患者中性粒细胞升至2.79×10^(9)/L,口腔溃疡愈合,未再腹泻。CN是一种常染色体显性遗传病,发病率低,临床表现缺乏特异性,分享该病例旨在提高临床医生对该病的认识,减少误诊率。

Microstructural characteristics and deformation of magnesium alloy AZ31 produced by continuous variable cross-section direct extrusion

Magnesium（Mg） alloy AZ31 was produced by continuous variable cross-section direct extrusion（CVCDE）to study its deformation behavior. Metallographic microscopy（OM）, transmission electron microscopy（TEM）, and scanning electron microscopy（SEM） were used to observe the variations in microstructure and fracture morphology of Mg alloy AZ31 as a function of processing methods. The results reveal that grains of Mg alloy AZ31 were refined and their microstructure was homogenized by CVCDE. The recrystallization in Mg alloy AZ31 produced by CVCDE with 2 interim dies was more complete than that produced by conventional extrusion（CE） and CVCDE with 1 interim die, and the grains were finer and more uniform.Plasticity of the AZ31 alloy was improved. Fracture mode was evolved from a combination of ductility and brittleness to a sole ductile form. In summary, a CVCDE mold structure with 2 interim dies can improve microstructure, plasticity, and toughness of Mg alloy AZ31.

Relationship between giant magnetoresistance of NiFe/Cu multilayers and their microstructures

The (111)_orientated NiFe/Cu multilayers were prepared by magnetron sputtering method. At room temperature, saturation magnetoresistances of NiFe/CU multilayers oscillate as a function of Cu spacer layer thickness. Two peak GMR values of 19 4%, 11 6% and 11 2%, 1% appear, respectively, at Cu sublayer thickness of t Cu =1 0, 2 2 nm while the deposition pressures are 0 25 and 0 45 Pa. X_ray small_angle reflections and diffuse scattering at Cu K_edge (8 979 keV) by synchrotron radiation source were used to characterize the interfacial roughness. Diffraction anomalous fine_structure scattering (DAFS) was performed to investigate the local structure of NiFe and Cu sublayers. Results show that the deposition pressure has effect on interfacial roughness of the samples obviously, and the interfacial roughness also affects the GMR values of the samples strongly.