Modulated illumination localization microscopy-enabled sub-10 nm resolution

Optical microscopy is an essential tool for exploring the structures and activities of cells and tissues.To break the limit of resolution caused by diffraction,researchers have made continuous advances and innovations to improve the resolution of optical microscopy since the 1990s.These contributions,however,still make sub-10nm imaging an obstacle.Here,we name a series of technologies as modulated illumination localization microscopy(MILM),which makes ultra-high-resolution imaging practical.Besides,we review the recent progress since 2017 when MINFLUX was proposed and became the inspiration and foundation for the follow-up devel-opment of MILM.This review divides MILM into two types:point-scanning and wide-field.The schematics,principles and future research directions of MILM are discussed elaborately.

Simply air:Vanadium-catalyzed oxidative kinetic resolution of methyl o-chloromandelate by ambient air

Vanadium-catalyzed oxidative kinetic resolution（OKR） of methyl o-chloromandelate 2a,key intermediate of the well-known oral antiplatelet agent（S）-clopidogrel,was achieved by ambient air for the first time.The air oxidation system,which was composed of vanadium and tridentate Schiff base ligands derived from amino alcohols and salicylaldehyde derivatives,afforded an efficient and economic approach to the target intermediate with high enantioselectivities（99%ee）.

新时代车辆工程专业人才培养方案研究

为满足新时代汽车行业新技术新业态对汽车专业人才的需求,应以“卓越工程师计划”的实践为基础,将新时代课程思政教育元素融入教育全过程,建立健全以现代产业学院或双创学院为平台的政校企三方协同的育人机制,培养未来新兴产业和新经济需要的实践能力强、创新能力强、具备国际竞争力的高素质新工科复合应用型车辆工程专业人才。

A molecular probe carrying anti-tropomyosin 4 for early diagnosis of cerebral ischemia/reperfusion injury

In vivo imaging of cerebral ischemia/reperfusion injury remains an important challenge.We injected porous Ag/Au@SiO_(2) bimetallic hollow nanoshells carrying anti-tropomyosin 4 as a molecular probe into mice with cerebral ischemia/reperfusion injury and observed microvascular changes in the brain using photoacoustic imaging with ultrasonography.At each measured time point,the total photoacoustic signal was significantly higher on the affected side than on the healthy side.Twelve hours after reperfusion,cerebral perfusion on the affected side increased,cerebrovascular injury worsened,and anti-tropomyosin 4 expression increased.Twenty-four hours after reperfusion and later,perfusion on the affected side declined slowly and stabilized after 1 week;brain injury was also alleviated.Histopathological and immunohistochemical examinations confirmed the brain injury tissue changes.The nanoshell molecular probe carrying anti-tropomyosin 4 has potential for use in early diagnosis of cerebral ischemia/reperfusion injury and evaluating its progression.

从“经文”到“经义”——“读书革命”视野中的近代读经法变异

清季新旧学术碰撞,今文经学崛起,读经方法成为学术论争的一大焦点。戊戌维新前后,康有为、梁启超师徒注重读书门径,提出“重义不重经文”的速成读法;同时期张之洞方面发布《劝学篇》,亦主张“经学通大义”为主的“守约”之法。癸卯学制确立“读经讲经”为中小学堂必不可少的科目,引出学堂体制下的新法读经和新体经学教科书。随着科举改废与新学流播,经学体系内原本融为一体的“经文”与“经义”开始在学者观念中分离;“读经法”的着眼点亦渐从文本记诵、文字训诂转向“微言大义”的求索或附会,对宋元以来文本取径的传统读书法带来致命的冲击。近代读经法的变异,伴随着白话文的兴起与新学科秩序的形成,问题已不限于读经本身,更关乎普遍意义上的教化实践与读写生活,预示着一场漫长“读书革命”(Leserevolution)的发端。

Novel technologies and models for studying pharmacological activities of traditional Chinese medicine for promoting blood circulation and removing blood stasis

OBJECTIVE Our previous studies demonstrated that various ingredients from the traditional Chinese medicine(TCM)for promoting blood circulation and removing blood stasis,as exemplified by cryptotanshinone and salvianolic acid B,exerted striking effects on modulating angiogenesis and vascular permeability,which suggests that they may be effective in treating vascular leak-driven diseases(e.g.tumor,cerebral cavernous malformation and diabetic retinopathy).However,the lack of reliable and advanced technologies and models sets up difficult hurdles for better understanding the role of TCM for promoting blood circulation and removing blood stasis.To this end,this study is to outline numerous cutting-edge platforms that can be utilized for exploring the function of TCM for promoting blood circulation and removing blood stasis in vascular leak-driven diseases.METHODS Two-photon laser scanning fluorescence microscopy was used to observe the interactions between neutrophils and blood vessels in a real-time manner.Dynamic flow system was employed to mimic the in vivo behaviors of neutrophils.RIP1-Tag5 spontaneous pancreatic cancer model was used to study the function of tumor blood vessels.CCM2ECKO(deletion of CCM2 in endothelial cells)mice were employed to establish the cerebral cavernous malformation(CCM)animal model.Micro-computed tomography(micro-CT)was utilized to assess the CCM lesion.Müller cell-knockout mouse model was used to study the progression of diabetic retinopathy.Vascular permeability in this model was assessed by fluorescein angiography.RESULTS The interactions between neutrophils and endothelial cells involve a series of complicated processes,including rolling,adhesion,intraluminal crawling and transmigration,which were all monitored in vivo by two-photon laser scanning fluorescence microscopy in a real-time manner.Dynamic flow system was capable of recapitulating the biological behaviors of neutrophils in vitro.Tumor vascular function in particular vascular perfusion could be assessed in the RIP1-Tag5 spontaneous pancreatic cancer model.In terms of CCM studies,specific deletion of CCM2 in endothelial cells resulted in the initiation of CCM lesion.The size and number of CCM lesions could be visualized and quantified by micro-CT.Furthermore,the Müller cell-knockout mouse model was able to precisely reflect the clinical symptoms of diabetic retinopathy.Vascular leak could be monitored at different time points using fluorescein angiography.CONCLUSION An array of high technologies and animal models can be used in investigating the occurrence and progression of multiple vascular leak-driven diseases.The pre-clinical and clinical studies of TCM for promoting blood circulation and removing blood stasis provide fundamental support for the application of the above-mentioned platforms,with the purpose of uncovering the scientific basis of TCM for promoting blood circulation and removing blood stasis.

KASP-SNP标记鉴别白菜自交系结球或非结球性状的应用

为提高传统结球型或非结球型白菜的育种效率,提高遗传分析的准确性和育种的有效性。利用SNP分子标记,选取KBr43、KBr111、KBr233和KBr258共4套引物,对206份白菜自交系,包括148份结球型白菜和58份非结球型白菜分别进行了KASP分析。KASP分析结果表明,KBr111或KBr2582套引物显示结球白菜与不结球白菜之间存在显著差异。在由3组引物KBr43、KBr111和KBr258标记的SNP位点组成的8个单倍基因型中,发现结球型白菜具有相对较高的ATG和ATC单倍基因型百分比,而非结球型白菜具有相对高的AGG或AGC单倍基因型比例。因此,我们推断,结球白菜更倾向于ATG和ATC单倍基因型,而非结球白菜更倾向于AGG和AGC单倍基因型。

丁香酸调控胆汁酸代谢和肠道屏障改善胆汁淤积肝病的研究

目的基于胆汁酸代谢和肠道屏障探讨丁香酸对胆汁淤积小鼠的调控作用。方法20只小鼠随机分为对照组、模型组和丁香酸低、高剂量(70、140 mg·kg^(-1))组。连续7 d灌胃给予相应药物,于第5天给药2 h后腹腔注射α-萘异硫氰酸酯(ANIT)诱导肝内胆汁淤积小鼠模型。末次给药后,记录小鼠体质量及肝质量变化;检测小鼠血清中肝功能指标、组织病理学变化,qPCR验证小鼠结肠组织中紧密连接蛋白闭锁小带蛋白-1(ZO-1)、闭合蛋白(Occludin)、紧密连接蛋白-5(Claudin-5)mRNA的表达,采用非靶向代谢组学分析血清中代谢产物的变化,检测肝脏和粪便中总胆汁酸变化。结果丁香酸可以显著降低模型组小鼠血清中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)活性和总胆红素(TBIL)、直接胆红素(DBIL)水平(P<0.05,P<0.01),减轻肝脏损伤和坏死;降低模型组小鼠结肠的淋巴细胞浸润,恢复隐窝形态。丁香酸高剂量组能显著升高结肠中ZO-1、Occludin、Claudin-5的mRNA表达水平(P<0.05);显著上调11个代谢物,下调29个代谢物,代谢产物主要涉及次生代谢物的生物合成、次级胆汁酸生物合成和胆汁分泌通路。丁香酸降低肝脏中总胆汁酸含量及增加粪便总胆汁酸的排出(P<0.05,P<0.01)。结论丁香酸可以显著改善胆汁淤积小鼠肠道屏障的受损,并且促进胆汁酸的代谢,这可能是丁香酸改善胆汁淤积的关键调控环节。

肢体运动训练对多发性骨髓瘤化疗致周围神经病变患者的影响

目的探讨基于周围神经病变的运动模式(Exercise for Peripheral Neuropathy,EPN)改良版肢体运动训练对多发性骨髓瘤化疗致周围神经病变患者生活质量及周围神经病变的改善效果。方法将多发性骨髓瘤化疗致周围神经病变患者61例按随机数字表法分为对照组和干预组。对照组进行常规基础运动训练,干预组进行EPN改良版肢体运动训练,持续4周。干预前后对两组生活质量、神经病变严重程度进行比较。结果共59例患者(干预组31例,对照组28例)完成研究。干预后,干预组生活质量得分(107.23±12.21)分,周围神经病变严重程度得分[7.00(7.00,9.00)]分,对照组分别为(95.04±15.11)分、[9.00(9.00,10.00)]分,两组比较,差异有统计学意义(均P<0.05)。结论基于EPN改良版肢体运动训练能提高多发性骨髓瘤化疗致周围神经病变患者生活质量,有效改善其周围神经病变情况,且简便易行,安全有效。

靶向血小板的抗肿瘤药物研究进展

血小板长期以来一直被认为是止血和血栓形成的关键参与者;然而,越来越多的证据表明,它们也与癌症有关。临床前和临床研究表明,血小板可以通过血小板和癌细胞之间的各种串扰来促进肿瘤发生和转移。血小板在肿瘤发生的各个阶段,包括肿瘤生长、肿瘤细胞外渗和转移中都发挥着积极的作用。此外,癌症患者的血小板增多与患者不良生存率相关。由于大量的微粒和外泌体,血小板还能够很好地协调局部和远处的肿瘤-宿主之间的相互作用。因此,以血小板为靶点的抗肿瘤药物具有很大的开发与应用前景。以下将对靶向血小板的抗肿瘤药物研究进展进行综述。

基本公共服务均等化推进共同富裕的实证研究

共同富裕是社会主义的本质要求,是中国式现代化的重要特征,而基本公共服务均等化是实现共同富裕的基础保障和重要手段。基于中国式现代化背景构建指标体系测算中国2012—2020年各省份和地级市层面共同富裕和基本公共服务均等化水平,并使用三维Kernel核密度图描述二者的动态演进。在此基础上,采用双向固定效应模型进行实证分析,发现基本公共服务均等化水平的提高有利于推进共同富裕目标的实现。进一步研究发现,在不同区域、不同水平和不同路径下,基本公共服务均等化对共同富裕的推进作用存在异质性。

Predicting short-term major postoperative complications in intestinal resection for Crohn’s disease:A machine learning-based study

BACKGROUND Due to the complexity and numerous comorbidities associated with Crohn’s disease(CD),the incidence of postoperative complications is high,significantly impacting the recovery and prognosis of patients.Consequently,additional stu-dies are required to precisely predict short-term major complications following intestinal resection(IR),aiding surgical decision-making and optimizing patient care.AIM To construct novel models based on machine learning(ML)to predict short-term major postoperative complications in patients with CD following IR.METHODS A retrospective analysis was performed on clinical data derived from a patient cohort that underwent IR for CD from January 2017 to December 2022.The study participants were randomly allocated to either a training cohort or a validation cohort.The logistic regression and random forest(RF)were applied to construct models in the training cohort,with model discrimination evaluated using the area under the curves(AUC).The validation cohort assessed the performance of the constructed models.RESULTS Out of the 259 patients encompassed in the study,5.0%encountered major postoperative complications(Clavien-Dindo≥III)within 30 d following IR for CD.The AUC for the logistic model was 0.916,significantly lower than the AUC of 0.965 for the RF model.The logistic model incorporated a preoperative CD activity index(CDAI)of≥220,a diminished preoperative serum albumin level,conversion to laparotomy surgery,and an extended operation time.A nomogram for the logistic model was plotted.Except for the surgical approach,the other three variables ranked among the top four important variables in the novel ML model.CONCLUSION Both the nomogram and RF exhibited good performance in predicting short-term major postoperative complic-ations in patients with CD,with the RF model showing more superiority.A preoperative CDAI of≥220,a di-minished preoperative serum albumin level,and an extended operation time might be the most crucial variables.The findings of this study can assist clinicians in identifying patients at a higher risk for complications and offering personalized perioperative management to enhance patient outcomes.

基于转矩定量分析的VSG低频特性校正方法

首先建立虚拟同步发电机(VSG)的虚拟转矩模型,通过虚拟转矩的定量分析揭示导致VSG低频特性发生变化的主要因素:次同步谐振对VSG的低频特性产生耦合影响和锁相环的负阻尼效应。在论证增加阻尼抑制次同步谐振可行性的基础上,给出稳态阻尼、动态阻尼联合取值方法,而后指出动态阻尼对VSG性能的影响;论证通过相位补偿法抑制低频振荡的可行性,通过对VSG转矩的定量校正,保证VSG的性能指标与设计预期一致。最后通过实验验证理论分析的正确性和设计方法的有效性。

新《公司法》与职工权益维护

2023年修订并于2024年7月1日起施行的《中华人民共和国公司法》(以下简称“新《公司法》”)内容修订多、变动大,特别是增加了保护职工合法权益的立法宗旨,完善了民主管理的相关规定,要求建立健全以职工代表大会为基本形式的民主管理制度,规定职工通过多种途径参与公司治理,为进一步维护职工合法权益提供了法律依据。为做好新《公司法》的宣传和阐释,探索工会工作的制度衔接,更好地实现职工权益保护的政策目标,本刊特邀专家学者以“新《公司法》与职工权益维护”为主题,着重从新《公司法》修改所涉及的职工权益保护、职工董监事制度、企业民主管理、工会制度衔接等视角展开研究探讨。

TRP家族调控黑色素的研究进展

黑色素是由黑色素细胞产生的一种天然色素,也是构成动物颜色的主要成分之一。黑色素的形成过程涉及多个基因的调控,因此仍存在许多未知问题。瞬时受体电位(transient receptor potential,TRP)通道家族位于细胞膜,调节Ca^(2+)、Mg^(2+)等阳离子的摄入,这一功能对于TRP家族在黑色素沉着调节中具有重要意义。通过总结发现,TRPM1、TRPM2、TRPA1、TRPV1在黑色素调控中发挥关键作用,TRPM3可能参与黑色素调控。TRPM1通过Ca^(2+)/CaMKIIδ/AKT途径促进黑色素瘤的发展,在正常皮肤组织中可能通过p53-TRPM1/miR-211-MMP9途径调控黑色素沉着。TRPM2可能通过TRPM2-Ca^(2+)-CaMKII-ROS途径促进黑色素细胞死亡。TRPM3可能与miR-204协同调控黑色素。TRPA1通过促进F-肌动蛋白重塑和PAR-2/CYLD途径促进角质形成细胞中的黑色素体吞噬作用,并且TRPA1可能协同cAMP或NO信号通路来刺激黑素细胞中的黑素生成。本文总结了TRP家族在黑色素细胞、黑色素瘤细胞和角质形成细胞中对黑色素调控的作用,为进一步揭示TRP家族对黑色素调节的机制提供参考。

A General Framework for Intelligent IoT Data Acquisition and Sharing in an Untrusted Environment Based on Blockchain

Traditional Io T systems suffer from high equipment management costs and difficulty in trustworthy data sharing caused by centralization.Blockchain provides a feasible research direction to solve these problems. The main challenge at this stage is to integrate the blockchain from the resourceconstrained Io T devices and ensure the data of Io T system is credible. We provide a general framework for intelligent Io T data acquisition and sharing in an untrusted environment based on the blockchain, where gateways become Oracles. A distributed Oracle network based on Byzantine Fault Tolerant algorithm is used to provide trusted data for the blockchain to make intelligent Io T data trustworthy. An aggregation contract is deployed to collect data from various Oracle and share the credible data to all on-chain users. We also propose a gateway data aggregation scheme based on the REST API event publishing/subscribing mechanism which uses SQL to achieve flexible data aggregation. The experimental results show that the proposed scheme can alleviate the problem of limited performance of Io T equipment, make data reliable, and meet the diverse data needs on the chain.

Aggressive fibromatosis of the sigmoid colon:A case report

BACKGROUND Aggressive fibromatosis(AF),also known as desmoid tumor or desmoid-type fibromatosis,is a rare soft tissue neoplasm that can occur in almost any part of the body.Although it is a benign disease,AF is aggressive and infiltrative and has a high recurrence rate after surgery.Common sites for intra-abdominal AF are the small bowel mesentery,retroperitoneum,and pelvis.AF in the colon is extremely rare.CASE SUMMARY Here,we report the first case of sigmoid colon AF,which was accidentally discovered in a 27-year-old woman during laparoscopic myomectomy.Computed tomography confirmed a slightly enhanced mass in the sigmoid colon.Subsequent colonoscopy did not reveal a mass in the colonic lumen,but a suspected external compress was found in the sigmoid colon.Surgical disease involving a gastrointestinal stromal tumor was suspected.The patient underwent laparoscopic exploration,and sigmoidectomy with a negative margin was performed to excise the mass.Postoperative immunohistochemistry revealed that the mass was an AF.The patient recovered well and was recurrence-free at the 30-month follow-up without adjuvant therapy.CONCLUSION AF should be considered in the differential diagnosis of subepithelial colon masses.Radical resection alone can achieve good outcomes.

阿拉伯胶、瓜尔豆胶复配对鸭血凝胶特性的影响

将阿拉伯胶、瓜尔豆胶及两者的复配胶分别添加到鸭血中,通过测定鸭血豆腐凝胶的质构特性、保水性并分析鸭血豆腐的微观结构,旨在阐述食用胶体对鸭血豆腐品质的影响。结果表明:两种食用胶均能极显著提高鸭血豆腐的硬度、弹性、回复性等质构特性和保水性能(P<0.01),其中阿拉伯胶对产品质构特性的影响高于瓜尔豆胶,而瓜尔豆胶对其保水性能的提升更为突出。阿拉伯胶与瓜尔豆胶复配使用具有协同增效作用,能够改善鸭血豆腐的凝胶特性,当复配质量比为7∶3,添加量为3.5 g/L时鸭血豆腐品质最佳,硬度、弹性与保水性分别达到4 217.33 g、0.88和66.97%。凝胶微观结构分析显示,食用胶的添加能够使鸭血豆腐形成连续、均一、致密的凝胶网络结构,显著提高了其凝胶性能与保水性。

黄酒米浆水中抗菌乳酸菌的筛选及特性分析

为了筛选黄酒米浆水中具有抗菌特性的乳酸菌,通过初筛和复筛实验分离、纯化了具有抗菌特性的乳酸菌,通过形态学观察、生理生化反应对菌株进行分类,通过有机酸干扰排除试验对所产抑菌物质进行初步分析。结果表明,从黄酒米浆水中筛选出36株对蜡样芽孢杆菌和大肠杆菌具有抑菌作用的乳杆菌,根据生理生化特征初步判断为植物乳杆菌、微小乳杆菌、鸟乳杆菌不解棉籽糖亚种乳杆菌、鼠李糖乳杆菌、马乳酒样乳杆菌、卷曲乳杆菌、嗜酸乳杆菌等。这些乳酸菌产生的抑菌物质非乳酸菌发酵产生的乳酸、乙酸和盐酸。本研究结果为黄酒米浆水中抑菌物质的开发及研究提供了基础。

基于“整体观”探讨中药的研究思维和方法

中药源于自然,治疗疾病有自身的优势和特点,其作用方式一直是中药研究者们不断研究和探索的重要内容。本文从中医的"整体观"对中药起效机制进行深入思考,认为中药成分多样可契合生物多靶,而生物靶标之间的协同作用是中药起效机制的重要补充;此外,中药对情志及肠道菌群稳态的调节作用也不容忽视,或许可为今后开展中药作用机制的研究提供新的思维和方法。