Repressing iron overload ameliorates central poststroke pain via the Hdac2-Kv1.2 axis in a rat model of hemorrhagic stroke

Thalamic hemorrhage can lead to the development of central post-stroke pain.Changes in histone acetylation levels,which are regulated by histone deacetylases,affect the excitability of neurons surrounding the hemorrhagic area.However,the regulato ry mechanism of histone deacetylases in central post-stroke pain remains unclea r.Here,we show that iron overload leads to an increase in histone deacetylase 2expression in damaged ventral posterolateral nucleus neurons.Inhibiting this increase restored histone H3 acetylation in the Kcna2 promoter region of the voltage-dependent potassium(Kv)channel subunit gene in a rat model of central post-stroke pain,thereby increasing Kcna2expression and relieving central pain.However,in the absence of nerve injury,increasing histone deacetylase 2 expression decreased Kcna2expression,decreased Kv current,increased the excitability of neurons in the ventral posterolateral nucleus area,and led to neuropathic pain symptoms.Moreover,treatment with the iron chelator deferiprone effectively reduced iron overload in the ventral posterolateral nucleus after intracerebral hemorrhage,reversed histone deacetylase 2 upregulation and Kv1.2 downregulation,and alleviated mechanical hypersensitivity in central post-stroke pain rats.These results suggest that histone deacetylase 2 upregulation and Kv1.2 downregulation,mediated by iron overload,are important factors in central post-stroke pain pathogenesis and co uld se rve as new to rgets for central poststroke pain treatment.

AAV mediated carboxyl terminus of Hsp70 interacting protein overexpression mitigates the cognitive and pathological phenotypes of APP/PS1 mice

The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control system.In this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s disease.We used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse brain.CHIP overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated tau.CHIP also alleviated the concentration of microglia and astrocytes around plaques.In APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin expression.Levels of HSP70 and HSP40,which have functional relevance to CHIP,were also increased.Single nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of CHIP.Our research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 mice.Indeed,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.

Solvent engineering towards scalable fabrication of high-quality perovskite films for efficient solar modules

Over the last decade,remarkable progress has been made in metal halide perovskite solar cells(PSCs),which have been a focus of emerging photovoltaic techniques and show great potential for commercialization.However,the upscaling of small-area PSCs to large-area solar modules to meet the demands of practical applications remains a significant challenge.The scalable production of high-quality perovskite films by a simple,reproducible process is crucial for resolving this issue.Furthermore,the crystallization behavior in the solution-processed fabrication of perovskite films can be strongly influenced by the physicochemical properties of the precursor inks,which are significantly affected by the employed solvents and their interactions with the solutes.Thus,a comprehensive understanding of solvent engineering for fabricating perovskite films over large areas is urgently required.In this paper,we first analyze the role of solvents in the solution-processed fabrication of large-area perovskite films based on the classical crystal nucleation and growth mechanism.Recent efforts in solvent engineering to improve the quality of perovskite films for solar modules are discussed.Finally,the basic principles and future challenges of solvent system design for scalable fabrication of high-quality perovskite films for efficient solar modules are proposed.

伏美替尼治疗携带EGFR敏感突变的原发广泛期小细胞肺癌案例表型分析

目的:探讨伏美替尼治疗携带表皮生长因子受体(epidermal growth factor receptor,EGFR)敏感突变的原发小细胞肺癌(small cell lung cancer,SCLC)的疗效,以及肿瘤基因组、转录组和免疫微环境的特点。方法:分析1例初诊为广泛期的SCLC,基因检测发现了EGFR19外显子缺失突变。患者在一线标准化疗进展后接受了第三代靶向药物伏美替尼治疗,获得疾病缓解,5个月的无进展生存。伏美替尼进展后肺部病灶再次活检,并进一步行基因组、转录组及肿瘤免疫微环境分析。结果:进展后活检再次证实SCLC的组织病理学诊断,基因检测仍然存在EGFR19外显子缺失突变。转录组学分析发现该例患者转录因子亚型符合SCLC-A型。患者治疗前后肿瘤突变负荷、PD-L1 TPS、肿瘤浸润CD4^(+)和CD8^(+)T细胞分布密度均较低,提示抑制性的免疫微环境。结论:携带EGFR敏感突变的广泛期SCLC具有独特的分子表型和肿瘤免疫微环境,伏美替尼可能是这类肿瘤的二线治疗选择之一。

STMN1表达与非小细胞肺癌预后价值的meta分析

背景与目的肺癌是全球发病率和死亡率最高的恶性肿瘤之一,严重危害人类健康,其中非小细胞肺癌(non-small cell lung cancer,NSCLC)占所有肺癌病例的85%以上。STMN1是一种广泛存在于细胞质中的微管解聚蛋白,其STMN1表达水平与NSCLC患者预后相关。本研究旨在通过meta分析探究STMN1表达水平对于肺癌预后的预测价值,筛选高敏感高特异性的生物标志物以优化肺癌患者全程管理。方法检索PubMed、The Cochrane Library、Embase、万方、知网等数据库建库至2024年9月6日发表的相关文献,采用纽卡斯尔-渥太华量表(Newcastle-Ottawa Scale,NOS)对文献质量进行评分。采用风险比(hazard ratio,HR)及对应的95%CI探究STMN1表达水平与NSCLC患者预后的相关性。预后指标包括总生存期(overall survival,OS)和无病生存期(disease-free survival,DFS)。所有统计分析由STATA 17.0软件完成。结果共纳入5项高质量研究(NOS评分≥6分),包括754例研究对象。Meta分析结果显示,STMN1过表达与NSCLC患者OS(HR=2.28,95%CI:1.79-2.91,P<0.001)和DFS(HR=2.14,95%CI:1.45-3.17,P<0.001)较差明显相关,STMN1表达是NSCLC患者预后不良的危险因素。结论STMN1过表达的NSCLC患者预后更差。STMN1表达水平可作为NSCLC患者的预后生物标志物,但上述结论仍需更多研究进一步论证。

小细胞肺癌多学科治疗进展

小细胞肺癌(small cell lung cancer,SCLC)恶性程度高、侵袭性强,治疗效果欠佳,预后差。通过多学科团队(multidisciplinary team,MDT)诊疗模式,制定个性化、多学科、综合治疗方案可有效提高SCLC患者的生存,改善患者生存质量。手术在极早期SCLC患者具有重要价值,局限期SCLC同步放化疗是基石治疗,免疫维持能进一步提高生存。免疫联合化疗在广泛期SCLC获得显著突破。随着放疗技术的进步和新的药物研发,新的放疗策略和药物治疗方案仍在不断探索和优化,在持续进步的同时也遗留许多问题和挑战。本文旨在全面梳理SCLC多学科治疗进展及策略。

ZnSe quantum dots downshifting layer for perovskite solar cells

To date, the instability of organometal halide perovskite solar cells（PSCs） has become the focus issue that limits the development and long-term application of PSCs. Both the ultraviolet（UV） rays in sunlight and moisture in air can significantly accelerate the disintegration of the perovskite. Here, we introduced a Zn Se quantum dots layer as downshifting materials, which was spin-coated onto the backside of PSCs.This layer converted the UV rays into visible light to prevent the destruction of PSCs as well as increase the light harvesting of the perovskite layer. Under the UV irradiation in the moisture ambient（40%）, the destruction speed of the unencapsulated perovskite films were also delayed evidently. In addition, the power conversion efficiency（PCE） of the PSCs was increased from 16.6% to 17.3% due to the increase of the visible light absorbance of the perovskite.

曲拉西利在广泛期小细胞肺癌中的应用进展

小细胞肺癌恶性程度高、易转移,治疗手段相对匮乏,预后较差。化疗的治疗地位不容忽视,但其常引起骨髓抑制,且补救性措施有时并不会立即起效,并增加新的不良反应风险。对于出现严重骨髓抑制的患者,只能延迟给药或中断治疗,进而影响疗效。曲拉西利(trilaciclib)是一款高效、选择性的CDK4/6抑制剂,在化疗前预防性给药,可诱导骨髓造血干/祖细胞暂时停滞在细胞周期的G1期,从而减少了暴露于化疗药物中造成的损伤。与单一谱系的刺激因子不同,在trilaciclib的作用下,减少了化疗导致的严重外周血中性粒细胞、红细胞以及血小板减少症的发生,并对淋巴系也起到保护作用,改善免疫微环境,提高患者治疗疗效。本文将对trilaciclib药理作用以及在小细胞肺癌中应用进行综述,旨在为临床提供更加全面客观的用药依据。

Filamentation initiated by Cas2 and its association with the acquisition process in cells

Cas1-and-Cas2-mediated new spacer acquisition is an essential process for bacterial adaptive immunity.The process is critical for the ecology of the oral microflora and oral health.Although molecular mechanisms for spacer acquisition are known,it has never been established if this process is associated with the morphological changes of bacteria.In this study,we demonstrated a novel Cas2-induced filamentation phenotype in E.coli that was regulated by co-expression of the Cas1 protein.A 30 amino acid motif at the carboxyl terminus of Cas2 is necessary for this function.By imaging analysis,we provided evidence to argue that Cas-induced filamentation is a step coupled with new spacer acquisition during which filaments are characterised by polyploidy with asymmetric cell division.This work may open new opportunities to investigate the adaptive immune response and microbial balance for oral health.

Design of a test structure based on chevron-shaped thermal actuator for in-situ measurement of the fracture strength of MEMS thin films

A novel test structure to characterize the fracture strength of MEMS(Micro-electro-Mechanical Systems)thin films is presented.The test structure is comprised of a micro fabricated chevron-shaped thermal actuator and test specimen.The test structure is capable of producing large displacement and stresswhile keeping a relatively low temperature gradient across the test specimen.A voltage is applied across the beams of the chevron-shaped actuator,producing thermal expansion force to fracture the test specimen.Actuator deflection is computed based on elastic analysis of structures.To verify the test structure,simulations have been implemented using COMSOL Multiphysics.A 620μmlong,410μm wide,10μm thick test structure produced stress of 7.1 GPawhile the applied voltage is 5 V.The results indicate that the test structure is suitable for in-situ measurement of the fracture strength of MEMS thin films.

A ROS-responsive hydrogel incorporated with dental follicle stem cell-derived small extracellular vesicles promotes dental pulp repair by ameliorating oxidative stress

Pulpitis,an inflammatory disease of dental pulp tissues,ultimately results in the loss of pulp defense properties.Existing clinical modalities cannot effectively promote inflamed pulp repair.Oxidative stress is a major obstacle inhibiting pulp repair.Due to their powerful antioxidative capacity,mesenchymal stem cell-derived small extracellular vesicles(MSC-sEVs)exhibit potential for treating oxidative stress-related disorders.However,whether MSC-sEVs shield dental pulp tissues from oxidative damage is largely unknown.Here,we showed that dental follicle stem cell-derived sEVs(DFSC-sEVs)have antioxidative and prohealing effects on a rat LPS-induced pulpitis model by enhancing the survival,proliferation and odontogenesis of H_(2)O_(2)-injured dental pulp stem cells(DPSCs).Additionally,DFSC-sEVs restored the oxidative/antioxidative balance in DPSC mitochondria and had comparable effects on ameliorating mitochondrial dysfunction with the mitochondrion-targeted antioxidant Mito-Tempo.To improve the efficacy of DFSC-sEVs,we fabricated an intelligent and injectable hydrogel to release DFSC-sEVs by combining sodium alginate(SA)and the ROS sensor RhB-AC.The newly formed SA-RhB hydrogel efficiently encapsulates DFSC-sEVs and exhibits controlled release of DFSC-sEVs in a HClO/ClO^(-)concentration-dependent manner,providing a synergistic antioxidant effect with DFSC-sEVs.These results suggest that DFSC-sEVs-loaded SA-RhB is a promising minimally invasive treatment for pulpitis by enhancing tissue repair in the pulp wound microenvironment.

Enhancing the Problem-Solving Skills of Vocational Students Through Skills Competition

Unlike general education,vocational education aims to nurture skilled people for various sectors in the society.The development of students’problem analysis and problem-solving skills is crucial.As an important part of the vocational education system,skills competitions are considered a“booster”for improving the quality of teaching in vocational institutions.This paper examines the problem-solving skills of students in preparation for skills competition.First of all,we introduce China’s education policies and conduct a review of early scholars’views,followed by a discussion on the specific problems faced in the design of the entry for skills competition and an exploration of the process of enhancing students’problem-solving skills around these problems;we then propose several suggestions for vocational institutions to enhance their participation in skills competitions.Skills competitions provide a“special stage”for students in vocational institutions to show their abilities.The question of how this“stage”can be utilized to better improve students’abilities is worth exploring in different fields.

Small extracellular vesicles derived from hypoxic preconditioned dental pulp stem cells ameliorate inflammatory osteolysis by modulating macrophage polarization and osteoclastogenesis

Extensive macrophage inflammatory responses and osteoclast formation are predominant during inflammatory or infective osteolysis.Mesenchymal stem cell(MSC)-derived small extracellular vesicles(MSC-sEV)have been shown to exert therapeutic effects on bone defects.However,cultured MSCs are typically exposed to normoxia(21%O2)in vitro,which differs largely from the oxygen concentration in vivo under hypoxic conditions.It is largely unknown whether sEV derived from dental pulp stem cells(DPSCs)cultured under hypoxic conditions(Hypo-sEV)exert better therapeutic effects on lipopolysaccharide(LPS)-induced inflammatory osteolysis than those cultured under normoxic conditions(Nor-sEV)by simultaneously inhibiting the macrophage inflammatory response and osteoclastogenesis.In this study,we show that hypoxia significantly induces the release of sEV from DPSCs.Moreover,Hypo-sEV exhibit significantly improved efficacy in promoting M2 macrophage polarization and suppressing osteoclast formation to alleviate LPS-induced inflammatory calvarial bone loss compared with Nor-sEV.Mechanistically,hypoxia preconditioning markedly alters the miRNA profiles of DPSC-sEV.MiR-210-3p is enriched in Hypo-sEV,and can simultaneously induce M2 macrophage generation and inhibit osteoclastogenesis by targeting NF-κB1 p105,which attenuates osteolysis.Our study suggests a promising potential for hypoxia-induced DPSC-sEV to treat inflammatory or infective osteolysis and identifies a novel role of miR-210-3p in concurrently hindering osteoclastogenesis and macrophage inflammatory response by inhibiting NF-kB1 expression.

Estimating leaf mercury content in Phragmites australis based on leaf hyperspectral reflectance

Introduction:Highmercury(Hg)concentrations affect the chlorophyll in leaves,therebymodifying leaf spectra.Hyperspectra is a promising technique for the rapid,nondestructive evaluation of leaf Hg content.In this study,we investigated Hg contents and reflective hyperspectra of reed leaves(Phragmites communis)in a gold mining(Jilin province,China).Spectral parameters sensitive to Hg content were identified through basic spectral transformations,continuous wavelet transformation(CWT),and spectral indices techniques.Leaf Hg inversion models were developed using stepwise multiple linear regression,partial least squares regression,and random forest algorithms.Outcomes:The results indicated that:1)leaf Hg content decreased with increasing distance from the mine:Jiapigou(JPG)>Erdaocha(EDC)>Laojingchang(LJC)>Erdaogou(EDG)>Lingqian(LQ)>Weishahe(WSH).2)Hg–sensitive wavelengths were primarily in the visible region;CWT increased the correlation between hyperspectral data and leaf Hg content,and improved the regression and accuracy of inversion;3)the continuumremoval–CWT–stepwise multiple linear regression was better for estimating low leaf Hg content;while the differential spectral index–partial least squares regression was better for estimating high leaf Hg content.Conclusion:These hyperspectral inversion methods could be used for rapid,nondestructive monitoring of wetland plants.

Electrolyte and interphase engineering through solvation structure regulation for stable lithium metal batteries

Lithium metal batteries(LMBs)are considered to be one of the most promising high-energy-density battery systems.However,their practical application in carbonate electrolytes is hampered by lithium dendrite growth,resulting in short cycle life.Herein,an electrolyte regulation strategy is developed to improve the cyclability of LMBs in carbonate electrolytes by introducing LiNO3 using trimethyl phosphate with a slightly higher donor number compared to NO_(3)^(-)as a solubilizer.This not only allows the formaion of Li^(+)-coordinated NO3 but also achieves the regulation of electrolyte solvation structures,leading to the formation of robust and ion-conductive solid-electrolyte interphase films with inorganic-rich inner and organic-rich outer layers on the Li metal anodes.As a result,high Coulombic efficiency of 99.1%and stable plating/stripping cycling of Li metal anode in LilCu cells were realized.Furthermore,excellent performance was also demonstrated in Li||LiNi_(0.83)Co_(0.11)Mn_(0.06)O_(2)(NCM83)full cells and Cul/NCM83 anodefree cells using high mass-loading cathodes.This work provides a simple interphase engineering strategy through regulating the electrolyte solvation structures for high-energy-density LMBs.

The Multi-field Coupled Vibration Analysis of AT-Cut Quartz Crystal Resonators with Parallelism Error

During the fabrication of quartz crystal resonators(QCRs),parallelism error is inevitably generated,which is rarely investigated.In order to reveal the influence of parallelism error on the working performance of QCRs,the coupled vibration of a non-parallel AT-cut quartz crystal plate with electrodes is systematically studied from the views of theoretical analysis and numerical simulations.The two-dimensional thermal incremental field equations are solved for the free vibration analysis via the coefficient-formed partial differential equation module of the COMSOL Multiphysics software,from which the frequency spectra,frequency–temperature curves,and mode shapes are discussed in detail.Additionally,the piezoelectric module is utilized to obtain the admittance response under different conditions.It is demonstrated that the parallelism error reduces the resonant frequency.Additionally,symmetry broken by the non-parallelism increases the probability of activity dip and is harmful to QCR’s thermal stability.However,if the top and bottom surfaces incline synchronously in the same direction,the influence of parallelism error is tiny.The conclusions achieved are helpful for the QCR design,and the methodology presented can also be applied to other wave devices.

Improvement of myocardial injury and gut microbiota disturbance in type 2 diabetic mice by inulin with various degrees of polymerization

This study is to explore the effects of low-performance inulin(SI,DP<10)and high-performance inulin(HI,DP>10)on myocardial injury in type 2 diabetic mice fed a high-fat diet(HFD)and its underlying mechanism.Six weeks of supplementation of type 2 diabetic mice with HI significantly improved blood glucose,insulin,and triglyceride levels in comparison with SI(p<0.05).HI had more advantageous effects in ameliorating myocardial injury by suppressing TNF-α,IL-1β,and CK-MB and promoting SDF-1βthan SI.Compared to SI,HI more significantly reduced the abundance of Firmicutes from 60.5%to 36.3%in type 2 diabetic mice fed a HFD and increased the abundance of Muribaculum,Blautia and Ruminococcaceae UCG-011 at the genus level(p<0.05).Metabolomics revealed that both SI and HI supplementation regulated tryptophan metabolism,bile acid metabolism,sphingolipid metabolism,and arachidonic acid metabolism,whereas HI supplementation increased prostaglandin h2 compared to SI.In summary,HI exhibited superior positive regulation of myocardial injury and gut microbiota dysfunction compared to SI.

Hollow engineering of sandwich NC@Co/NC@MnO_(2)composites toward strong wideband electromagnetic wave attenuation

Multiple hetero-interfaces would strengthen interfacial polarization and boost electromagnetic wave absorption,but still remain the formidable challenges in decreasing filler loadings.Herein,sandwich NC@Co/NC@MnO_(2)composites with hollow cavity,multiple hetero-interfaces,and hierarchical structures have been fabricated via the cooperative processes of self-sacrifice strategy and sequential hydrothermal reaction.In the sandwich composites,middle magnetic components(Co/NC)are wrapped by inner N-doped carbon(NC)matrix and outer hierarchical MnO_(2)nanosheets.Importantly,hollow engineering of sandwich composites with multiple hetero-interfaces greatly facilitates the enhancement of absorption bandwidth without sacrificing the absorption intensity.The maximum reflection loss of sandwich NC@Co/NC@MnO_(2)composites reaches-44.8 dB at 2.5 mm and the effective bandwidths is achieved as wide as 9.6 GHz at 2.3 mm.These results provide us a new insight into preparing efficient electromagnetic wave absorbers by interface engineering and hollow construction.

Polymorphism in the Hsa-miR-4274 seed region influences the expression of PEX5 and enhances radiotherapy resistance in colorectal cancer

Identifying biomarkers for predicting radiotherapy efficacy is crucial for optimizing personalized treatments.We previously reported that rs1553867776 in the miR-4274 seed region can predict survival in patients with rectal cancer receiving postoperative chemoradiation therapy.Hence,to investigate the molecular mechanism of the genetic variation and its impact on the radiosensitivity of colorectal cancer(CRC),in this study,bioinformatics analysis is combined with functional experiments to confirm peroxisomal biogenesis factor 5(PEX5)as a direct target of miR-4274.The miR-4274 rs1553867776 variant influences the binding of miR-4274 and PEX5 mRNA,which subsequently regulates PEX5 protein expression.The interaction between PEX5 and Ku70 was verified by co-immunoprecipitation and immunofluorescence.A xenograft tumor model was established to validate the effects of miR-4274 and PEX5 on CRC progression and radiosensitivity in vivo.The overexpression of PEX5 enhances radiosensitivity by preventing Ku70 from entering the nucleus and reducing the repair of ionizing radiation(IR)-induced DNA damage by the Ku70/Ku80 complex in the nucleus.In addition,the enhanced expression of PEX5 is associated with increased IR-induced ferroptosis.Thus,targeting this mechanism might effectively increase the radiosensitivity of CRC.These findings offer novel insights into the mechanism of cancer radioresistance and have important implications for clinical radiotherapy.

基于智能手机的即时检测

新冠肺炎疫情的爆发使人们对即时检测(POCT)的需求不断增加,而智能手机作为目前人类最离不开的工具,在POCT中具有巨大的应用潜力。基于智能手机的POCT有以下独特的优点:(1)操作简单,不需要专业培训;(2)无需长时间等待,可以及时获得测试结果;(3)制作成本低,有利于在资源有限地区使用。因此,基于智能手机的POCT正迅速成为传统实验室检测的潜在替代方法。在这里,我们以POCT所检测的对象(体液、挥发性有机化合物、生命体征)为分类的基础,并结合目前主流的传感策略,包括比色技术、荧光技术、电化学技术、压电传感、热电传感、超声传感、光电传感等,对近三年基于智能手机的传感器在POCT中的应用进行了全面的回顾。我们评估了这些传感器的性能以及发展潜力,此外,还介绍了POCT中使用的新兴技术,如纳米技术、柔性电子器件、微流体技术、生物可降解技术、自供能技术、多路检测等。最后,总结了目前基于智能手机的POCT面临的问题,并对其未来的发展进行了展望。