SWI/SNF复合体基因突变促进NSCLC细胞在NSI小鼠体内肝转移的研究

背景与目的SWI/SNF复合体(switch/sucrose nonfermentable chromatin-remodeling complex,SWI/SNF)是一种重要的染色质重塑复合物,其亚基变异在多种肿瘤中存在,并与多种肿瘤细胞生物学特征相关。但其基因突变是否参与非小细胞肺癌(non-small cell lung cancer,NSCLC)肝转移过程尚不清楚。本研究拟探究SWI/SNF复合体基因突变对NSCLC肝转移的影响及潜在机制。方法我们使用全外显子组测序(whole-exome sequencing,WES)分析了NSCLC细胞H1299、H23和H460中SWI/SNF复合体基因突变。通过CRISPR/Cas9(clustered regularly interspaced short palindromic repeats)技术构建了ARID1A基因稳定敲除的H1299细胞株,建立了小鼠模型模拟NSCLC肝转移,观察不同基因突变对肝转移的影响。利用RNA-Seq和蛋白印迹分析差异基因的表达,并通过免疫组化技术(immunohistochemistry,IHC)检测了SWI/SNF复合体调控的靶分子在小鼠肝转移灶中的表达。结果WES分析确定了SWI/SNF复合体基因的突变情况。动物实验结果显示SWI/SNF复合体基因突变与免疫缺陷小鼠较高的肝转移率相关。转录组测序和蛋白印迹分析显示SWI/SNF复合体基因突变细胞中ALDH1A1和APOBEC3B表达上调,尤其是ARID1A蛋白缺失的H460和H1299 sgARID1A中ALDH1A1表达水平显著上升。IHC染色亦显示H460和H1299 sgARID1A细胞肝转移灶中ALDH1A1高表达。结论本研究强调了SWI/SNF复合体基因ARID1A和SMARCA4等突变在促进肺癌细胞肝转移中的关键作用。这些基因突变可能通过促进ALDH1A1与APOBEC3B高表达进而发挥肝特异性转移的作用,为深入探究肺癌肝转移分子机制提供了新线索。

构件化数字教育资源工作室建设研究

在教育信息化和常态化疫情防控背景下,线上教学、线上线下混合式教学不断增多,凸显出数字教育资源建设和共享工作的重要性。文章基于高校在数字教育资源建设和共享方面的迫切需求,制定建设构件化数字教育资源工作室的方案;通过引入资源构件化方法,完成工作室系统分层框架设计和标准构件结构定义,进而对工作室软硬件进行统一的构件化分类和构件实例化;最终建成了可满足微课程创作、在线直播、远程互动等需求,并支持功能性能柔性扩展的构件化数字教育资源工作室。研究表明,构件化数字教育资源工作室通过将软硬件组成元素构件化、标准化,以积木组合方式组装构件,可良好实现设计功能,同时具有资源复用率高、支持功能性能柔性扩展、适应教育信息化发展需求等优点。

Key global climate governance problems and Chinese countermeasures

Presently,the full implementation of the negotiations and collaborations under the Paris Agreement faces new key problems and severe challenges.These problems and challenges include the following:how to honor the principle of“common but differentiated responsibilities”to facilitate a comprehensive,balanced,and effective implementation of the key elements of the Paris Agreement,such as adaptation,mitigation,finance,technology,capacity building,and transparency;how to uphold and maintain the status of China and other emerging countries as developing countries in light of the requirements of the United Nations Framework Convention on Climate Change and the historical responsibilities of these countries;and how to assess the goal of limiting the global temperature increase to 1.5℃and what constitutes an equitable carbon mitigation pathway for different types of countries.Developed countries and developing countries have drastically diverging views on carbon border adjustment measures for trade with developing countries proposed by several developed countries such as the European Union.Developed countries have demonstrated obvious intentions and actions designed to weaken and neglect the principle of“common but differentiated responsibilities”,to impose mitigation pressure on developing countries,to shift the responsibilities for emissions onto others,and to pass on the costs of mitigation.The maneuvering among different types of countries and interest groups has become increasingly intense.In response,China must maintain its strategic focus,adhere to the goals and principles established by the Paris Agreement,stick to its strategic positioning as a developing country,solidify strategic support from the developing world,and safeguard the legitimate rights and interests of developing countries.China played a conducive role in facilitating the Paris Agreement and has become an active participant,contributor,and leader in global climate governance.China must continue to follow Xi Jinping Thought on Socialism with Chinese Characteristics for a New Era and its conception of ecological civilization and the concept of building a community of common destiny,to actively lead the cooperation process in the construction of a global climate governance system characterized by equity,justice,and win-win collaborations,and to promote compliance with the Paris Agreement.At the same time,China should accelerate the green,low-carbon,circular transformation of its economy;accelerate the coordinated governance of the economy,environment,and climate change;and formulate and implement a long-term low-carbon development strategy.By the middle of the 21st century,while achieving the goal of building a great modern socialist country,China can also achieve a deep decarbonization development path that is in line with the goal of limiting the global temperature increase to well below 2°C and pursuing efforts to limit the increase to 1.5℃.

A Comprehensive Overview of the Neural Mechanisms of Light Therapy

Light is a powerful environmental factor influencing diverse brain functions.Clinical evidence supports the beneficial effect of light therapy on several diseases,including depression,cognitive dysfunction,chronic pain,and sleep disorders.However,the precise mechanisms underlying the effects of light therapy are still not well understood.In this review,we critically evaluate current clinical evidence showing the beneficial effects of light therapy on diseases.In addition,we introduce the research progress regarding the neural circuit mechanisms underlying the modulatory effects of light on brain functions,including mood,memory,pain perception,sleep,circadian rhythm,brain development,and metabolism.

Suppressor tRNA in gene therapy

Suppressor tRNAs are engineered or naturally occurring transfer RNA molecules that have shown promise in gene therapy for diseases caused by nonsense mutations,which result in premature termination codons(PTCs)in coding sequence,leading to truncated,often nonfunctional proteins.Suppressor t RNAs can recognize and pair with these PTCs,allowing the ribosome to continue translation and produce a full-length protein.This review introduces the mechanism and development of suppressor t RNAs,compares suppressor tRNAs with other readthrough therapies,discusses their potential for clinical therapy,limitations,and obstacles.We also summarize the applications of suppressor tRNAs in both in vitro and in vivo,offering new insights into the research and treatment of nonsense mutation diseases.

Climate change and Aedes albopictus risks in China:current impact and future projection

Background Future distribution of dengue risk is usually predicted based on predicted climate changes using general circulation models(GCMs).However,it is difficult to validate the GCM results and assess the uncertainty of the predictions.The observed changes in climate may be very different from the GCM results.We aim to utilize trends in observed climate dynamics to predict future risks of Aedes albopictus in China.Methods We collected Ae.albopictus surveillance data and observed climate records from 80 meteorological stations from 1970 to 2021.We analyzed the trends in climate change in China and made predictions on future climate for the years 2050 and 2080 based on trend analyses.We analyzed the relationship between climatic variables and the prevalence of Ae.albopictus in different months/seasons.We built a classification tree model(based on the average of 999 runs of classification and regression tree analyses)to predict the monthly/seasonal Ae.albopictus distribution based on the average climate from 1970 to 2000 and assessed the contributions of different climatic variables to the Ae.albopictus distribution.Using these models,we projected the future distributions of Ae.albopictus for 2050 and 2080.Results The study included Ae.albopictus surveillance from 259 sites in China found that winter to early spring(November–February)temperatures were strongly correlated with Ae.albopictus prevalence(prediction accuracy ranges 93.0–98.8%)—the higher the temperature the higher the prevalence,while precipitation in summer(June–September)was important predictor for Ae.albopictus prevalence.The machine learning tree models predicted the current prevalence of Ae.albopictus with high levels of agreement(accuracy>90%and Kappa agreement>80%for all 12 months).Overall,winter temperature contributed the most to Ae.albopictus distribution,followed by summer precipitation.An increase in temperature was observed from 1970 to 2021 in most places in China,and annual change rates varied substantially from-0.22℃/year to 0.58℃/year among sites,with the largest increase in temperature occurring from February to April(an annual increase of 1.4–4.7℃ in monthly mean,0.6–4.0℃ in monthly minimum,and 1.3–4.3℃ in monthly maximum temperature)and the smallest in November and December.Temperature increases were lower in the tropics/subtropics(1.5–2.3℃ from February–April)compared to the high-latitude areas(2.6–4.6℃ from February–April).The projected temperatures in 2050 and 2080 by this study were approximately 1–1.5℃ higher than those projected by GCMs.The estimated current Ae.albopictus risk distribution had a northern boundary of north-central China and the southern edge of northeastern China,with a risk period of June–September.The projected future Ae.albopictus risks in 2050 and 2080 cover nearly all of China,with an expanded risk period of April–October.The current at-risk population was estimated to be 960 million and the future at-risk population was projected to be 1.2 billion.Conclusions The magnitude of climate change in China is likely to surpass GCM predictions.Future dengue risks will expand to cover nearly all of China if current climate trends continue.

中国碳中和技术发展路径

Carbon neutrality has been considered a new focus of countries for achieving the goal of the Paris Agreement.China has pledged to peak CO_(2) emissions before 2030 and achieve carbon neutrality before 2060,and a"1+N"policy framework has been built to guide the implementations.Scientific and technological innovation has been emphasized as one of the key strategies to establish an innovation system,strengthen research,and promote applications of green and low-carbon technologies[1].Despite numerous studies and policies on decarbonization technologies,studies focusing on technological development pathways for China’s carbon neutrality are needed[2].

Hyperosmolarity promotes macrophage pyroptosis by driving the glycolytic reprogramming of corneal epithelial cells in dry eye disease

Tear film hyperosmolarity plays a core role in the development of dry eye disease(DED)by mediating the disruption of ocular surface homeostasis and triggering inflammation in ocular surface epithelium.In this study,the mechanisms involving the hyperosmolar microenvironment,glycolysis mediating metabolic reprogramming,and pyroptosis were explored clinically,in vitro,and in vivo.Data from DED clinical samples indicated that the expression of glycolysis and pyroptosis-related genes,including PKM2 and GSDMD,was significantly upregulated and that the secretion of IL-1βsignificantly increased.In vitro,the indirect coculture of macrophages derived from THP-1 and human corneal epithelial cells(HCECs)was used to discuss the interaction among cells.The hyperosmolar environment was found to greatly induce HCECs’metabolic reprogramming,which may be the primary cause of the subsequent inflammation in macrophages upon the activation of the related gene and protein expression.2-Deoxy-d-glucose(2-DG)could inhibit the glycolysis of HCECs and subsequently suppress the pyroptosis of macrophages.In vivo,2-DG showed potential efficacy in relieving DED activity and could significantly reduce the overexpression of genes and proteins related to glycolysis and pyroptosis.In summary,our findings suggested that hyperosmolar-induced glycolytic reprogramming played an active role in promoting DED inflammation by mediating pyroptosis.

光干预降低可卡因记忆消退后复吸行为的神经环路机制

毒品成瘾已经成为一个严峻挑战,特别是因滥用造成的可卡因高复吸率给社会带来严重负担。尽管我们在神经生物学层面对成瘾的理解取得了显著进展,但仍缺乏有效降低复吸的戒断手段.在这项研究中,我们发现在可卡因戒断期实施亮光干预(BLT)并结合消退训练可防止可卡因驱动的复吸行为,该效应是通过丘脑-外侧核通路所介导。实验证实,在可卡因戒断进程中,外侧核(LHb)被激活,而通过BLT抑制LHb可减少可卡因驱动的复吸行为:本文阐明了BLT的作用是通过激活投射至LHb的腹外侧膝状体和膝状体间小叶(VLGN/IGL)神经元或抑制该通路中突触后LHb神经元实现。此外,BLT可以改善药物戒断引起的负性情绪。本研究结果表明在可卡因戒断期间施加BLT可能成为一种实现药物戒除的有效手段.

眼表微环境与泪膜稳态对视觉质量影响的新认识

2020年发布的中国干眼专家共识第一次将眼表微环境的概念新增到了干眼的定义中。强调了泪膜不稳定和眼表微环境失衡在干眼发病机制中的重要地位,并将视功能障碍作为干眼病情发展的重要结局之一。为了加强对新共识的认识,推动相关的基础与临床研究的开展及转化,为广大干眼患者提供更为细致的诊疗建议,专家组于2021年3年26日在江西吉安召开讨论会,对眼表微环境和泪膜稳态这两方面的研究现状及存在的问题进行分析,主要围绕干眼的这两个核心机制的新认识、与视觉质量的关系、临床的评估和治疗手段的建议和未来发展新方向等提出建议和推荐意见。

Hierarchical 3D mesoporous silicon@graphene nanoarchitectures for lithium ion batteries with superior performance

Silicon has been recognized as the most promising anode material for high capacity lithium ion batteries. However, large volume variations during charge and discharge result in pulverization of Si electrodes and fast capacity loss on cycling. This drawback of Si electrodes can be overcome by combination with well-organized graphene foam. In this work, hierarchical three-dimensional carbon-coated mesoporous Si nanospheres@graphene foam （C@Si@GF） nanoarchitectures were successfully synthesized by a thermal bubble ejection assisted chemical-vapor-deposition and magnesiothermic reduction method. The morphology and structure of the as-prepared nanocomposites were characterized by field emission scanning electron microscopy, transmission electron microscopy and Raman spectroscopy. When employed as anode materials in lithium ion batteries, C@Si@GF nanocomposites exhibited superior electrochemical per- formance including a high specific capacity of 1,200 mAh/g at the current density of 1A/g, excellent high rate capabilities and an outstanding cyclability. Post-mortem analyses identified that the morphology of 3D C@Si@GF electrodes after 200 cycles was well maintained. The synergistic effects arising from the combination of mesoporous Si nanospheres and graphene foam nanoarchitectures may address the intractable pulverization problem of Si electrode.

The adaptive strategies of yaks to live in the Asian highlands

The yak(Bos grunniens),an indigenous herbivore raised at altitudes between 3,000 and 5,000 m above sea level,is closely linked to more than 40 ethnic communities and plays a vital role in the ecological stability,livelihood security,socio-economic development,and ethnic cultural traditions in the Asian highlands.They provide the highlanders with meat,milk,fibres,leather and dung(fuel).They are also used as pack animals to transport goods,for travel and ploughing,and are important in many religious and traditional ceremonies.The Asian highlands are known for an extremely,harsh environment,namely low air temperature and oxygen content and high ultraviolet light and winds.Pasture availability fluctuates greatly,with sparse pasture of poor quality over the long seven-month cold winter.After longterm natural and artificial selections,yaks have adapted excellently to the harsh conditions:1)by genomics,with positively selected genes involved in hypoxia response and energy metabolism;2)anatomically,including a short tongue with a weak sense of taste,and large lung and heart;3)physiologically,by insensitivity to hypoxic pulmonary vasoconstriction,maintaining foetal haemoglobin throughout life,and low heart rate and heat production in the cold season;4)behaviourlly,by efficient grazing and selecting forbs with high nutritional contents;5)by low nitrogen and energy requirements for maintenance and low methane emission and nitrogen excretion,namely,‘Low-Carbon’and‘Nitrogen-Saving’traits;6)by harboring unique rumen microbiota with a distinct maturation pattern,that has coevolved with host metabolism.This review aims to provide an overview of the comprehensive adaptive strategies of the yak to the severe conditions of the highlands.A better understanding of these strategies that yaks employ to adapt to the harsh environment could be used in improving their production,breeding and management,and gaining benefits in ecosystem service and a more resilient livelihood to climate change in the Asian highlands.

Encapsulation of selenium sulfide in double-layered hollow carbon spheres as advanced electrode material for lithium storage

Selenium sulfide/double-layered hollow carbon sphere （SeS2/DLHC） composites have been designed as high-performance cathode materials for novel Li-SeS2 batteries. In the constructed composite, SeS2 is predominantly encapsulated in the interlayer space of DLHCs with a high loading of 75% （weight percentage） and serves as the active component for lithium storage. The presence of Se in the composite and the carbon framework not only alleviate the shuttling of polysulfide, but also improve the conductivity of electrodes. Migration of active materials from the interlayer void to the hollow cavity of DLHCs after cycling, which further mitigates the loss of active materials and the shuttle effect, is observed. As a result, the SeS2/DLHC composite delivers a high specific capacity （930 mA.h.g-1 at 0.2 C） and outstanding rate capability （400 mA.h.g-1 at 6 C）, which is much better than those of SeS2/single-layered hollow carbon sphere, Se/DLHC, and S/DLHC composites. Notably, the SeS2/DLHC composite shows an ultralong cycle life with 89% capacity retention over 900 cycles at 1 C, or only 0.012% capacity decay per cycle. Our study reveals that both SeS2 and the double-layered structures are responsible for the excellent electrochemical performance.

Tailoring mesoporous-silica nanoparticles for robust immobilization of lipase and biocatalysis

The rational design of nano-carriers is critical for modem enzyme immobilization for advanced biocatalysis. Herein, we report the synthesis of octadecylalkyl- modified mesoporous-silica nanoparticles （C18-MSNs） with a high C18 content （-19 wt.%） and tunable pore sizes （1.6--13 nm）. It is demonstrated that the increased hydrophobic content and a tailored pore size （slightly larger than the size of lipase） are responsible for the high performance of immobilized lipase. The optimized C18-MSNs exhibit a loading capacity of 711 mg/g and a specific activity 5.23 times higher than that of the free enzyme. Additionally, 93% of the initial activity is retained after reuse five times, which is better than the best performance reported to date. Our findings pave the way for the robust immobilization of lipase for biocatalytic applications.

Effect of building interface form on thermal Check foi comfort in gymnasiums in hot and humid climates

The thermal environment and thermal comfort of a building are greatly affected by the desig n of the build ing interface form. Most con temporary architectural designs con sider only the relations between architectural form and architectural beauty. Few studies on the correlati on of architectural form and thermal comfort address the in flue nee of architectural form on thermal comfort and thermal environment. These studies are particularly important for gymnasium architectures located in hot and humid areas, which have high requirements for thermal comfort. This paper presents an experimental investigati on and an an alysis of the effect of the building in terface form of gymnasiums on thermal comfort in hot and humid subtropical regions during summer. Results showed that the influence of the top interface forms on thermal comfort is mainly dominated by the mea n radiant temperature, which could be con trolled to improve thermal comfort. The in fluence of side interface forms on thermal comfort is mainly domi nated by air velocity, and thermal comfort could be improved by promoting natural ventilation on the side interface form design to reduce indoor heat. This research enhanced our understanding of the relation between the in terface form and the thermal comfort of gymnasiums. In addition, this paper provides a theoretical reference for the sustainable design of gymnasiums in hot and humid climates.

Effects of different structural parameters and the medium environment on plasmonic lattice resonance formed by Ag nanospheres on SiO2 nanopillar arrays

The effects of the diameter of SiO2 nanopillars,the diameter of Ag nanospheres,the arrays’period,and the medium environment on the plasmonic lattice resonance(PLR)formed by Ag nanospheres on SiO2 nanopillar arrays are systematically investigated.Larger diameters of SiO2 nanopillars with other parameters kept constant will widen the PLR peak,redshift the PLR wavelength,and weaken the PLR intensity.Larger diameters of Ag nanospheres with other parameters kept constant will widen the PLR peak,redshift the PLR wavelength,and strengthen the PLR intensity.Larger array periods or larger refractive index of medium environment corresponds to larger PLR wavelengths.

Calcium-Impermeable NMDA Receptor:A Novel Target for Addiction

Drug addiction results in long-term synaptic potentiation at excitatory synapses in the brain reward circuitry,especially in the ventral tegmental area（VTA）and nucleus accumbens（NAc）,central parts of the mesolimbic dopamine system,and then progresses to other cortical regions[1,2].

Meeting the Dual Goals of Content Knowledge and English Language Learning:A Study of the CCUEI Curriculum Materials

This article reports a study on the China-Canada-United States English Immersion(CCUEI)Moral Education and Social Studies(MESS)curriculum materials for elementary classes(Grades 3-6)with the aim of learning how the curriculum addressed the dual goals of MESS content and English language learning.An analysis comparing the CCUEI third grade MESS textbook with an equivalent level Chinese textbook demonstrates how China’s national standards in MESS and English education can be met,and drawbacks encountered in the process.The CCUEI textbook was found to embrace grade level MESS content standards,but showed a varied degree of depth of content across standards.The textbook addressed all of the general goals of Level One English language learning(Grades 3-4)and most of the language skills indicators(16 out of 20).An additional in-depth teacher survey provided a user’s perspective on MESS materials.The teachers rated the textbook highly for its activity-centered format and knowledge-rich content.They emphasized the importance of teaching English language as preparation for the MESS content teaching,and asked for more systematic support in language teaching from curriculum materials.