Observetion of major organs deadaptation change after returning to lower altitude in Qinghai-Tibet railway construction population

High altitude deadaptation affects the health of population returned to the plain. We examined major physiological functions in 348 healthy control subjects and 626 Qinghai-Tibet railway construction workers who returned to the plain from the Qinghai-Tibet plateau. Blood indices, such as hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin concentration and platelet larger cell ratio, of the returned group that had stayed at high altitude more than 3 years were significantly higher than those of the control group. Red blood cell distribution width and platelet were significantly lower in the returned group than in the control group. Compared to the control group, five years after returning to the plain, the returned group had higher mean corpuscular hemoglobin and lower red blood cell distribution width. Detection rate of hypotension and low pulse pressure were significantly higher in the returned group than in the control group at 20 months after the return, and cardiothoracic ratio was significantly higher in the returned group than in the control group at 40 months after the return. Short-term memory function was significantly lower in the returned group than in the control group. Total triiodothyronine and thyroid-stimulating hormone were significantly lower, but total thyroxine and free triiodothyronine were significantly higher in the returned group than in the control group. Sex hormones level returned to normal level in the returned group. Superoxide dismutase was significantly higher and malondialdehyde was significantly lower in the returned group than in the control group. Fatty acid binding protein was significantly higher in the returned group than in the control group, and this difference maintained with time after the return. We conclude that physiological functions of most organs in returned population after exposed to high altitude can not be completely restored to the normal level in a short period of time.

藏东南大气中多环芳烃的污染特征及来源分析

为探究青藏高原东南部大气中多环芳烃(Polycyclic Aromatic Hydrocarbons,简称PAHs)的污染、源及输送特征,利用鲁朗地区(29.77°N,94.73°E)总悬浮颗粒物(Total Suspended Particles,简称TSP)和大气中的14种PAHs含量,结合同期气象环境数据进行了综合分析。结果表明,该地区TSP中PAHs和气相的PAHs质量浓度变化范围分别为0.22~5.05 ng m^(-3)和0.83~63.75 ng m^(-3),平均值分别为2.13 ng m^(-3)和11.33 ng m^(-3)。薪柴和柴油的燃烧是污染的主要方式,汽油燃烧等其他排放为次要方式。PAHs来自本地污染和远距离传输(Long Range Transmission,简称LRT)共同的影响。本地污染在四季各个源地均不相同。冬春季本地污染大,源在东南及正南方,夏秋季受本地和外来输送共同作用,本地源在东南方且占比小,LRT占比大。LRT受西北气流、西风气流和西南气流三支气流影响,污染严重时西南气流占主导,西风气流次之,污染较轻时西风气流或西北气流占主导,西北气流所传输的污染最少。该研究结果加深了对藏东南区域PAHs变化、输送特征的认识,为该区域大气污染治理提供了理论依据。

Recent developments in application of single-cell RNA sequencing in the tumour immune microenvironment and cancer therapy

The advent of single-cell RNA sequencing(scRNA-seq)has provided insight into the tumour immune microenvironment(TIME).This review focuses on the application of scRNA-seq in investigation of the TIME.Over time,scRNA-seq methods have evolved,and components of the TIME have been deciphered with high resolution.In this review,we first introduced the principle of scRNA-seq and compared different sequencing approaches.Novel cell types in the TIME,a continuous transitional state,and mutual intercommunication among TIME components present potential targets for prognosis prediction and treatment in cancer.Thus,we concluded novel cell clusters of cancerassociated fibroblasts(CAFs),T cells,tumour-associated macrophages(TAMs)and dendritic cells(DCs)discovered after the application of scRNA-seq in TIME.We also proposed the development of TAMs and exhausted T cells,as well as the possible targets to interrupt the process.In addition,the therapeutic interventions based on cellular interactions in TIME were also summarized.For decades,quantification of the TIME components has been adopted in clinical practice to predict patient survival and response to therapy and is expected to play an important role in the precise treatment of cancer.Summarizing the current findings,we believe that advances in technology and wide application of single-cell analysis can lead to the discovery of novel perspectives on cancer therapy,which can subsequently be implemented in the clinic.Finally,we propose some future directions in the field of TIME studies that can be aided by scRNA-seq technology.

Dimethyl sulfide,a metabolite of the marine microorganism,protects SH-SY5Y cells against 6-hydroxydopamine and MPP~＋-induced apoptosis

Dimethyl sulfide(DMS)has been historically recognized as a metabolite of the marine microorganism or a disgusting component for the smell of halitosis patients.In our recent study,DMS has been identified as a cytoprotectant that protects against oxidative-stress induced cell death and aging.We found that at near-physiological concentrations,DMS reduced reactive oxygen species(ROS)in cultured PC12 cells and alleviated oxidative stress.The radical-scavenging capacity of DMS at near-physiological concentration was equivalent to endogenous methionine(Met)-centered antioxidant defense.Methionine sulfoxidereductase A(MsrA),the key antioxidant enzyme in Met-centered defense,bound to DMS and promoted its antioxidant capacity via facilitating the reaction of DMS with ROS through a sulfonium intermediate at residues Cys72,Tyr103,Glu115,followed by the release of dimethyl sulfoxide(DMSO).MTT assay and trypan blue test indicated that supplement of DMS exhibited cytoprotection against 6-hydroxydopamine and MPP+induced cell apoptosis.Furthermore,Msr A knockdown abolished the cytoprotective effect of DMS at near-physiological concentrations.The present study reveals new insight into the potential therapeutic value of DMS in Parkinson disease.

Concept,Grouping and Subgrouping of Ecological Technology

Although modern technology has an important role in human economic and social development,it can result in significant ecological damage.Thus,research has begun to focus on so-called"ecological technologies"to repair the degraded land and fragmented ecological environment and build a green mode of production and development.However,the concept of"ecological technology"is currently ill-defined,given the many different research fields involved.Therefore,here we divide ecological technologies into broad versus narrow technologies in terms of their impact on economic and social development and the related needs of production and ecological governance.We redefine each concept and clarify their aims and extensions,before further dividing them into three groups and seven subgroups,and clarifying the functions of each.The grouping and subgrouping of ecological technology will lay a foundation for the technology selection,collocation,implementation,promotion,monitoring and evaluation of ecological engineering planning and design.

Pipeline血流导向装置与传统支架辅助栓塞治疗颈内动脉未破裂中小型动脉瘤的疗效比较分析

目的评价Pipeline血流导向装置(Pipeline flow diverter,PED)治疗未破裂颈内动脉中小型动脉瘤的安全性及有效性。方法收集2018年1月至2022年2月我院神经介入科采用PED及支架辅助弹簧圈栓塞(stent-assisted coiling,SAC)治疗的53例颈内动脉未破裂动脉瘤患者的临床资料,并进行回顾性分析及组间对比。分别采用O Kelly Marotta(OKM)分级及Raymond分级评估术后即刻及随访时动脉瘤的栓塞程度;采用改良Rankin量表评分(mRS)评价患者围手术期及随访时的神经功能;介入治疗术后3个月开始采用DSA或CTA随访复查动脉瘤的闭塞情况及支架通畅情况。结果共有符合纳入标准患者53例,其中PED 31例,SAC 22例。两组患者性别、年龄等基线数据均无统计学差异。PED组34枚动脉瘤的术后即刻DSA显示造影剂明显滞留,OKM A级9枚(26.4%),B级7枚(20.6%),C级14枚(41.2%),D级4枚(11.8%)。SAC组24枚动脉瘤的术后即刻DSA显示,RaymondⅠ级16枚(66.7%),Ⅱ级7枚(29.1%),Ⅲ级1枚(4.2%)。手术时间在PED组和SAC组之间存在显著统计学差异(P=0.003<0.05),围手术期出现不良事件为9例,PED组4例,SAC组5例,两组之间差异无统计学意义(P=0.49)。PED组术后平均随访时间为(6.4±1.8)个月(范围:5~12个月);SAC组术后平均随访时间为(10.4±9.0)个月(范围:2~30个月)。对术后动脉瘤闭塞情况进行观察,PED组完全闭塞28例(84.8%),SAC组完全闭塞17例(77.3%)。SAC组术后复发4例,PED组未见术后复发。术后随访中所有患者预后良好,mRS≤2,无出血或缺血导致的术后不良事件发生。结论使用PED治疗颈内动脉未破裂中小型动脉瘤可以缩短手术时间,具有不弱于支架辅助栓塞治疗的动脉瘤完全闭塞率及安全性,且在避免术后复发方面具有明显优势,但长期疗效仍需进一步的随访观察。

Applications of human amniotic fluid stem cells in wound healing

Complete wound regeneration preserves skin structure and physiological functions,including sensation and perception of stimuli,whereas incomplete wound regeneration results in fibrosis and scarring.Amniotic fluid stem cells(AFSCs)would be a kind of cell population with self-renewing and non-immunogenic ability that have a considerable role in wound generation.They are easy to harvest,culture,and store;moreover,they are non-tumorigenic and not subject to ethical restrictions.They can differentiate into different kinds of cells that replenish the skin,subcutaneous tissues,and accessory organs.Additionally,AFSCs independently produce paracrine effectors and secrete them in exosomes,thereby modulating local immune cell activity.They demonstrate anti-inflammatory and immunomodulatory properties,regulate the physicochemical microenvironment of the wound,and promote full wound regeneration.Thus,AFSCs are potential resources in stem cell therapy,especially in scar-free wound healing.This review describes the biological characteristics and clinical applications of AFSCs in treating wounds and provide new ideas for the treatment of wound healing.

Delivery of an Rhs-family nuclease effector reveals direct penetration of the gram-positive cell envelope by a type VI secretion system in Acidovorax citrulli

The type VI secretion system(T6SS)is a double-tubular nanomachine widely found in gram-negative bacteria.Its spear-like Hcp tube is capable of penetrating a neighboring cell for cytosol-to-cytosol protein delivery.However,gram-positive bacteria have been considered impenetrable to such T6SS action.Here we report that the T6SS of a plant pathogen,Acidovorax citrulli(AC),could deliver an Rhsfamily nuclease effector RhsB to kill not only gram-negative but also gram-positive bacteria.Using bioinformatic,biochemical,and genetic assays,we systematically identified T6SS-secreted effectors and determined that RhsB is a crucial antibacterial effector.RhsB contains an N-terminal PAAR domain,a middle Rhs domain,and an unknown C-terminal domain.RhsB is subject to self-cleavage at both its N-and C-terminal domains and its secretion requires the upstream-encoded chaperone EagT2 and VgrG3.The toxic Cterminus of RhsB exhibits DNase activities and such toxicity is neutralized by either of the two downstream immunity proteins,RimB1 and RimB2.Deletion of rhsB significantly impairs the ability of killing Bacillus subtilis while ectopic expression of immunity proteins RimB1 or RimB2 confers protection.We demonstrate that the AC T6SS not only can effectively outcompete Escherichia coli and B.subtilis in planta but also is highly potent in killing other bacterial and fungal species.Collectively,these findings highlight the greatly expanded capabilities of T6SS in modulating microbiome compositions in complex environments.

SOURCES OF FOREIGN LANGUAGE ANXIETY:TOWARDS A FOUR-DIMENSION MODEL

In the past three decades,the study of foreign language anxiety has attracted the attention of an increasing number of researchers and language teachers.Studies in a variety of language learning contexts have found that approximately one-third of students studying a foreign language experience at least a moderate level of foreign language anxiety.Research has also reported various types of negative effects of foreign language anxiety on foreign language learning.Since foreign language anxiety is not only prevalent among language learners,but appears to interfere with language learning,it must be taken seriously in all types of language instruction.Most language teachers are interested in the causes of foreign language anxiety so that they can create more comfortable language learning environments.Although sources of foreign language anxiety have been identified here and there across the literature,there has not been a systematic and comprehensive report of all the sources.This paper attempts to propose a four-dimension source model of foreign language anxiety based on a thorough literature review and the researcher' s own insights.

Access to pyridines via cascade nucleophilic addition reaction of 1,2,3-triazines with activated ketones or acetonitriles

We studied the cascade nucleophilic addition reactions of 1,2,3-triazines with activated acetonitriles or ketones,which were used to construct highly substituted pyridines that are not easily accessed by conventional methods.The strategy addressed some structural diversity issues currently facing medicinal chemistry,and the resulting pyridines could be used as convenient precursors for the synthesis of related pharmaceuticals.In particular,our method was applied to the syntheses of the marketed drug etoricoxib and several biologically important molecules in a few steps.

Acid-catalyzed ring-expansion of 4-(1-hydroxycyclobutyl)-1,2,3-triazoles

We here report a direct ring-opening/semipinacol rearrangement reaction of 4-(1-hydroxycyclobutyl)-1,2,3-triazole,in which N-acyl substituted 1,2,3-triazole was generated in situ and would trigger thermo-dynamically controlled electrocyclization ring-opening to afford a rearrangement precursor(α-diazo-ol).This strategy avoided the usage of metal catalysts and the reservation of sulfonyl groups on the N^(1)-posi-tion of 1,2,3-triazole.The final cycloenaminone product is highly reactive and could be commonly used as a dinucleophilic acceptor to synthesize structurally diverse fused bicyclic products.