mTOR调控T细胞增殖与功能的研究进展

雷帕霉素机制性靶蛋白(mTOR)在细胞生长、增殖、分化等多个方面起关键作用。T淋巴细胞是人体免疫系统的重要组成,本文总结了mTOR如何通过糖代谢和脂质代谢等代谢途径来调控T细胞功能,并探讨了mTOR在T细胞分化中的关键性作用。此外,本文还归纳了近年来天然化合物通过作用于mTOR来调控T细胞的研究进展,这些发现有望为未来以mTOR为靶点的疾病治疗提供新的思路和方法。

风寒湿外邪作用于EPO影响痹证(类风湿关节炎)的发生

目的明确风寒湿外邪作用于促红细胞生成素(EPO)影响痹证(类风湿关节炎)的发生机制。方法(1)30只雄性SD大鼠随机分为正常对照组、单纯完全弗氏佐剂(CFA)组、风寒湿+CFA组,每组10只大鼠。单纯CFA组大鼠正常饲养14 d,风寒湿+CFA组大鼠风寒湿刺激14 d,再尾根部皮下注射0.1 mL含100μg热灭活结核杆菌(Mtb)的CFA诱导佐剂性关节炎(AIA)。分别于实验前、风寒湿刺激14 d及CFA免疫后7 d尾动脉取血,采用ELISA法检测血清EPO含量。(2)30只雄性SD大鼠随机分为单纯CFA组、风寒湿+CFA组、风寒湿+CFA+rhEPO组,每组10只大鼠。单纯CFA组正常饲养14 d,风寒湿+CFA组、风寒湿+CFA+rhEPO组,风寒湿刺激14 d,再尾根部皮下注射0.1 mL含100μg Mtb的CFA诱导AIA。风寒湿+CFA+rhEPO组自风寒湿刺激第1天起,尾静脉注射重组人促红细胞生成素(rhEPO)。观察大鼠的发病时间和发病率;CFA免疫后8 d,腹主动脉取血,采用ELISA法检测血清TNF-α含量。(3)选取RA寒湿痹阻证伴慢性疾病性贫血患者、RA寒湿痹阻证伴缺铁性贫血患者、RA寒湿痹阻证无贫血患者及健康志愿者各20例,取静脉血,采用ELISA法检测血清EPO含量。结果(1)风寒湿刺激14 d及CFA免疫后7 d,风寒湿+CFA组大鼠血清EPO水平明显低于正常对照组大鼠和单纯CFA组大鼠(P<0.05)。(2)风寒湿+CFA+rhEPO组大鼠AIA发病时间和发病率与单纯CFA组相比无显著差异;风寒湿+CFA+rhEPO组大鼠血清TNF-α含量显著低于风寒湿+CFA组大鼠(P<0.01),而与单纯CFA组相比无显著性差异。(3)RA寒湿痹阻证伴慢性病贫血患者血清EPO含量显著高于健康志愿者(P<0.01),但却显著低于RA寒湿痹阻证伴缺铁性贫血组(P<0.05)。结论风寒湿外邪通过抑制EPO表达而影响痹证(类风湿关节炎)的发生。

自噬在天然药物活性成分抗心血管衰老中的作用

心血管系统维持着机体正常的生命活动,心血管系统衰老可引发高血压、动脉粥样硬化、心力衰竭、心肌梗死等疾病。自噬是一种溶酶体依赖性降解途径,其水平随着年龄增加而逐渐降低,一方面提高机体自噬可延缓细胞和组织衰老,另一方面自噬水平的过度激活可诱导细胞自噬性死亡、加速衰老。某些天然药物活性成分能调节自噬,并改善心血管系统衰老。它们可能是通过调节细胞自噬发挥对心血管系统衰老的保护作用。因此,文章就自噬在天然药物活性成分延缓心血管系统衰老中的作用及研究进展进行综述。

Age-hardening behavior and microstructure of Cu-15Ni-8Sn-0.3Nb alloy prepared by powder metallurgy and hot extrusion

Cu-15Ni-8Sn-0.3Nb alloy rods were prepared by means of powder metallurgy followed by hot extrusion.Element maps obtained by electron probe micro analyzer(EPMA)showed that Nb-rich phases were formed and distributed within grains and at grain boundaries of the Cu-15Ni-8Sn-0.3Nb alloy.Transmission electron microscope(TEM)results indicated that there was no obvious orientation relationship between these phases and the matrix.Spinodal decomposition and ordering transformation appeared at early stages of aging at400°C and caused significant strengthening.Cu-15Ni-8Sn-0.3Nb alloy exhibited both higher strength(ultimate tensile strength>1030MPa)and higher tensile ductility(elongation>9.1%)than Cu-15Ni-8Sn alloy after aging treatment.The improvement was caused by Nb-rich phases at grain boundaries which led o the refinement of grain size and postponed the growth of discontinuous precipitates during aging.

Serum levels of mi RNA in patients with hepatitis B virus-associated acute-on-chronic liver failure

Background: Hepatitis B virus(HBV)-associated acute-on-chronic liver failure(HBV-ACLF) is a lifethreatening condition and its exact pathophysiology and progression remain unclear. The present study aimed to assess the role of serum mi RNAs in the evaluation of HBV-ACLF and to develop a model to predict the outcomes for ACLF.Methods: Serum was collected from 41 chronic hepatitis B and 55 HBV-ACLF patients in addition to30 chronic asymptomatic HBV carriers as controls. The mi RNAs expressions were measured by real-time quantitative PCR(q-PCR). Statistical analyses were conducted to assess the ability of differentially expressed mi RNAs and other prognostic factors in identifying ACLF prognosis and to develop a new predictive model.Results: Real-time q-PCR indicated that serum miR-146 a-5 p, mi R-122-3 p and mi R-328-3 p levels were significantly upregulated in ACLF patients compared to chronic hepatitis B and chronic asymptomatic HBV carriers patients. In addition, multivariate regression analyses indicated that Na+, INR, gastrointestinal bleeding and mi R-122-3 p are all independent factors that are reliable and sensitive to the prognosis of HBV-ACLF. Therefore, we developed a new model for the prediction of HBV-ACLF disease state: Y = 0.402 × Na+-1.72 × INR-4.963 × gastrointestinal bleeding(Yes = 0; No = 1)-0.278 ×(mi R-122-3 p) + 50.449. The predictive accuracy of the model was 95.3% and the area under the receiver operating characteristic curve(AUROC) was 0.847.Conclusions: Expression levels of these mi RNAs(miR-146 a-5 p, mi R-122-3 p and mi R-328-3 p) positively correlate with the severity of liver inflammation in patients with ACLF and may be useful to predict HBV-ACLF severity.

Degradation of simulated organic wastewater by advanced oxidation with oxidants generated from oxygen reduction

The degradation capacity of advanced oxidants generated from oxygen reduction was investigated in model effluent containing chlorobenzene, aniline and benzene through the advanced oxidation processes(AOPs). Intermediate products of the degradation process were determined by GC–MS, and they contributed to specify the degradation pathways of monoaromatic compounds. The study particularly focused on the influence of the dosage of the oxidant, pH and the initial concentration of organic compounds on the degradation effectiveness.When the dosage of oxidant was 4 wt% and the pH was 7, the maximum degradation rates of 74.83% chlorobenzene, 70.32% aniline and 37.69% benzene were achieved. Furthermore, microwave was applied to intensify the oxidation process under optimal operation conditions, and the degradation rates were increased to 87.85% chlorobenzene, 89.11% aniline and 39.03% benzene, respectively.

Emerging MoS_(2)Wafer-Scale Technique for Integrated Circuits

As an outstanding representative of layered materials,molybdenum disulfide(MoS_(2))has excellent physical properties,such as high carrier mobility,stability,and abundance on earth.Moreover,its reasonable band gap and microelectronic compatible fabrication characteristics makes it the most promising candidate in future advanced integrated circuits such as logical electronics,flexible electronics,and focal-plane photodetector.However,to realize the all-aspects application of MoS_(2),the research on obtaining high-quality and large-area films need to be continuously explored to promote its industrialization.Although the MoS_(2)grain size has already improved from several micrometers to sub-millimeters,the high-quality growth of wafer-scale MoS_(2)is still of great challenge.Herein,this review mainly focuses on the evolution of MoS_(2)by including chemical vapor deposition,metal–organic chemical vapor deposition,physical vapor deposition,and thermal conversion technology methods.The state-of-the-art research on the growth and optimization mechanism,including nucleation,orientation,grain,and defect engineering,is systematically summarized.Then,this review summarizes the wafer-scale application of MoS_(2)in a transistor,inverter,electronics,and photodetectors.Finally,the current challenges and future perspectives are outlined for the wafer-scale growth and application of MoS_(2).

Active Machine Learning for Chemical Engineers:A Bright Future Lies Ahead!

By combining machine learning with the design of experiments,thereby achieving so-called active machine learning,more efficient and cheaper research can be conducted.Machine learning algorithms are more flexible and are better than traditional design of experiment algorithms at investigating processes spanning all length scales of chemical engineering.While active machine learning algorithms are maturing,their applications are falling behind.In this article,three types of challenges presented by active machine learning—namely,convincing the experimental researcher,the flexibility of data creation,and the robustness of active machine learning algorithms—are identified,and ways to overcome them are discussed.A bright future lies ahead for active machine learning in chemical engineering,thanks to increasing automation and more efficient algorithms that can drive novel discoveries.

Changes in tumor-antigen expression profile as human small-cell lung cancers progress

Objective： Our group has previously observed that in patients with small-cell lung cancers （SCLCs）, the expression of a tumor antigen, glioma big potassium （gBK） ion channel, is higher at the time of death than when the cancer is first treated by surgical resection. This study aimed to determine whether this dichotomy was common in other potential lung tumor antigens by examining the same patient samples using our more extensive profile analysis of tumor-antigen precursor protein （TAPP）. We then tested the hypothesis that therapeutic intervention may inadvertently cause this increased gBK production. Methods： SCLC samples （eight surgical resections and three autopsy samples） and three control lungs were examined by quantitative real-time polymerase chain reaction for 42 potential TAPPs that represent potential T-cell-mediated immunological targets. Results： Twenty-two TAPP mRNAs displayed the same profile as gBK, i.e., more mRNAs were expressed at autopsy than in their surgical counterparts. B-cyclin and mouse double minute 2, human homolog of PS3-binding protein were elevated in both autopsy and surgical specimens above the normal-lung controls. When HTB119 cells were incubated with doxorubicin, gBK was strongly induced, as confirmed by intracellular flow cytometry with a gBK-specific antibody. Conclusion： Our findings suggested that more immunological targets became available as the tumor responded to chemotherapy and proceeded toward its terminal stages.

偶数长度的几乎平衡且不相关的四元序列对

通过把Z_(N)^(*)划分成四个子集,利用交错技术提出了一种关于长度为2N的不相关四元序列对的一般构造方法。通过选择基于Z_(p)的阶为4或8的分圆类,构造了长度为2p的,几乎平衡且不相关的,除少数相位外自相关性低的四元序列对。

Hilbert类多项式在素域F_(p)上的分解

设D为模4余0或1的负整数,令O=O_(D)为虚二次域K=q(√D)中判别式等于D的序.熟知Hilbert类多项式HD(x)是O的j不变量j_(D)=j(C/O)在K上的最小多项式.令n_(D)=(O_(Q(j_(D))):Z[j_(D)])表示Z[j_(D)]在Q(j_(D))的整数环O_(Q(j_(D)))中的指数.设p为任意素数.如果p|n_(D),或者者p|D在K中惯性且n_(D)的p-进离散赋值v_(p)(n_(D))≤3,则本文完全确定了H_(D)(x)在多项式环F_(p)[x]中的因式分解.

Intervention effects of Naoxintong capsules on psychological and cardiac status in depressed rats after heart failure

Background:Depression is a common clinical phenomenon in the patients with heart failure(HF).In traditional Chinese medicine(TCM),diseases in the brain and heart are thought to be correlated and interact.Naoxintong capsules(NXT)has been used for treating cardio-cerebrovascular diseases,while its therapeutic effect on depression after HF remains unclear.Objective:The aim of the study is to evaluate the intervention effect of NXT on depression after HF.Methods:Sprague-Dawley rats were assigned into the following 5 groups:sham,model,NXT(250,1000 mg/kg),and valsartan(8mg/kg).Coronary artery occlusion was performed to induce HF and subsequent depression in rats.The cardiac function was evaluated by echocardiography,hematoxylin-eosin staining,and Masson trichrome staining.The sucrose preference test and Morris water maze test were carried out to assess the depressive behaviors in rats.The ultrastructure of hippocampal CA1 neurons was observed and the levels of corticotropin-releasing hormone in the hypothalamus,brain-derived neurotrophic factor in the cortex,and adrenocorticotropic hormone(ACTH)in the plasma were determined by enzyme-linked immunosorbent assay.The levels of dopamine,5-hydroxytryptamine,norepinephrine,andγ-aminobutyric acid in the hippocampus were measured by UPLC-QQQ-MS.Results:NXT reduced myocardial injury and pathological changes in the cardiac tissue and increased the left ventricular ejection fraction,left ventricular fractional shortening,and cardiac output.NXT increased the sugar preference rate and number of crossings and shortened the escape latency.Furthermore,the NXT treatment restored the levels of corticotropin-releasing hormone,adrenocorticotropic hormone,brain-derived neurotrophic factor,dopamine,andγ-aminobutyric acid to the baseline values.Conclusions:NXT not only demonstrates cardioprotective effect but also attenuates depression in the rats after HF.It may exert the antidepressant effect by inhibiting the hyperactivity of the hypothalamic-pituitary-adrenal axis and recovering the levels of neurotrophic factors and neurotransmitters.

Recommendations for the diagnosis and treatment of paroxysmal kinesigemc dyskinesia: an expert consensus in China

Paroxysmal dyskinesias are a group of neurological diseases characterized by intermittent episodes of involuntary movements with different causes.Paroxysmal kinesigenic dyskinesia(PKD)is the most common type of paroxysmal dyskinesia and can be divided into primary and secondary types based on the etiology.Clinically,PKD is characterized by recurrent and transient attacks of involuntary movements precipitated by a sudden voluntary action.The major cause of primary PKD is genetic abnormalities,and the inheritance pattern of PKD is mainly autosomal-dominant with incomplete penetrance.The proline-rich transmembrane protein 2(PRRT2)was the first identified causative gene of PKD,accounting for the majority of PKD cases worldwide.An increasing number of studies has revealed the clinical and genetic characteristics,as well as the underlying mechanisms of PKD.By seeking the views of domestic experts,we propose an expert consensus regarding the diagnosis and treatment of PKD to help establish standardized clinical evaluation and therapies for PKD.In this consensus,we review the clinical manifestations,etiology,clinical diagnostic criteria and therapeutic recommendations for PKD,and results of genetic analyses in PKD patients performed in domestic hospitals.

Abel p-分歧扭子群和新Cohen-Lenstra猜想

本文首先回顾数域K的Abel p-分歧理论特别是其T_(p)-群,并给出一般Cohen-Lenstra猜想的架构.对于全体实(虚)二次域及其几类子族,本文提出T_(p)(K)的分布满足新的Cohen-Lenstra猜想.后者解释了Shanks等(1999)对于2-进L函数特殊值的分布猜测,并给出基本单位迹的分布猜想.本文给出理论结果和计算数据来支持这些猜想.

Shape Memory Alloy Helical Microrobots with Transformable Capability towards Vascular Occlusion Treatment

Practical implementation of minimally invasive biomedical applications has been a long-sought goal for microrobots.In this field,most previous studies only demonstrate microrobots with locomotion ability or performing a single task,unable to be functionalized effectively.Here,we propose a biocompatible shape memory alloy helical microrobot with regulative structure transformation,making it possible to adjust its motion behavior and mechanical properties precisely.Especially,towards vascular occlusion problem,these microrobots reveal a fundamental solution strategy in the mechanical capability using shape memory effect.Such shape-transformable microrobots can not only manipulate thrust and torque by structure to enhance the unclogging efficiency as a microdriler but also utilize the high work energy to apply the expandable helical tail as a selfpropulsive stent.The strategy takes advantage of untethered manipulation to operate microsurgery without unnecessary damage.This study opens a route to functionalize microrobots via accurate tuning in structures,motions,and mechanical properties.

Influences of fiber length and water film thickness on fresh properties of basalt fiber-reinforced mortar

In plain mortar,the water film thickness(WFT)has been found to play a key role in the fresh properties.However,in fiber-reinforced mortar,the role of WFT has not been investigated yet.In this research,basalt fibers of different lengths were added to the mortar,and the dynamic and static flowability,cohesiveness,adhesiveness,and packing density were tested to study the effects of fiber length on the packing density and WFT,and the combined effects of fiber length and WFT on the fresh properties.The results showed that in fiber-reinforced mortar,the WFT also plays a key role,whereas the fiber length exerts its influences through the indirect effects on the packing density and WFT and the direct effect on fiber-mortar interaction.Basically,an increase in fiber length decreases the packing density and WFT,decreases the dynamic and static flowability needed for placing,increases the cohesiveness needed for avoiding segregation,and,quite unexpectedly,decreases the adhesiveness needed for rendering and spraying applications.Regression analysis yielded good correlation of the fresh properties to fiber length and WFT,and best-fit formulas for the mix design for basalt fiber-reinforced mortar were obtained.

Absorption mechanism of paeonol nanoemulsion using in vitro intestinal cell models

The use of nano emulsion has improved the bioavailability of paeonol, and that is mainly because of the P-glycoprotein (P-gp)-mediated efflux described in our previous study. However, other mechanisms involved in the intestinal absorption of paeonol nanoemulsion are still unknown. Therefore, we aimed to investigate additional paeonol nanoemulsion absorption mechanisms. By establishing the Caco-2 cells model and the follicle-associated epithelium (FAE) model, uptake studies and bidirectional transport of paeonol nanoemulsion in the presence of different efflux inhibitors were conducted to observe its intake and transport. The paracellular pathway was evaluated by fluorescent staining of Occludin, and the expressions of efflux proteins and tight junction proteins were detected by Western blotting analysis. In this study, we found that nanoemulsion improved the absorption of paeonol by increasing its uptake across the Caco-2 and FAE cells and by reducing the expressions of efflux proteins. In addition, paeonol nanocmulsion had no effect on the opening of tight junctions. The results showed that the absorption of paeonol nanoemulsion occurred by passive diffusion in the Caco-2 cell mode! and by endocytosis in the FAE model, which was related to multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP) efflux. Paeonol nanoemulsion significantly in creased the absorption of the drug in intestinal cells, which was possibly related to the increase in intestinal cell uptake, inhibited expressions of efflux protein and reduction of drug efflux.

On abelian 2-ramification torsion modules of quadratic fields

For a number field F and a prime number p, the Z_(p)-torsion module of the Galois group of the maximal abelian pro-p extension of F unramified outside p over F, denoted by T_(p)(F), is an important subject in the abelian p-ramification theory. In this paper, we study the group T_(2)(F) = T_(2)(m) of the quadratic field F = Q(m_(1/2)). Firstly, assuming m > 0, we prove an explicit 4-rank formula for quadratic fields that rk4(T_(2)(-m))= rk2(T_(2)(-m))-rank(R), where R is a certain explicitly described Rédei matrix over F_(2). Furthermore, using this formula, we obtain the 4-rank density formula of T_(2)-groups of imaginary quadratic fields. Secondly, for l an odd prime, we obtain the results about the 2-power divisibility of orders of T_(2)(±l) and T_(2)(±2l), both of which are cyclic 2-groups. In particular, we find that #T_(2)(l) ≡ 2#T_(2)(2l) ≡ h_(2)(-2l)(mod 16) if l ≡ 7(mod 8),where h_(2)(-2l) is the 2-class number of Q((-2l)_(1/2)). We then obtain the density results for T_(2)(±l) and T_(2)(±2l)when the orders are small. Finally, based on our density results and numerical data, we propose distribution conjectures about T_(p)(F) when F varies over real or imaginary quadratic fields for any prime p, and about T_(2)(±l)and T_(2)(±2l) when l varies, in the spirit of Cohen-Lenstra heuristics. Our conjecture in the T_(2)(l) case is closely connected to Shanks-Sime-Washington’s speculation on the distributions of the zeros of 2-adic L-functions and to the distributions of the fundamental units.

A Simple Proof of Dieudonn-Manin Classification Theorem

The Dieudonne Manin classification theorem on φ-modules （φ-isocrystals） over a perfect field plays a very important role in p-adic Hodge theory. In this note, in a more general setting we give a new proof of this result, and in the course of the proof, we also give an explicit construction of the Harder Narasimhan filtration of a φ-module.

The Universal Kolyvagin Recursion Implies the Kolyvagin Recursion

Let Hz. be the universal norm distribution and M a fixed power of prime p. By using the double complex method employed by Anderson, we study the universal Kolyvagin recursion occurring in the canonical basis in the cohomology group H^0（Gz,Hz/MHz）. We furthermore show that the universal Kolyvagin recursion implies the Kolyvagin recursion in the theory of Euler systems. One certainly hopes this could lead to a new way to find new Euler systems.