Visualizing Wallerian degeneration in the corticospinal tract after sensorimotor cortex ischemia in mice

Stroke can cause Wallerian degeneration in regions outside of the brain,particularly in the corticospinal tract.To investigate the fate of major glial cells and axons within affected areas of the corticospinal tract following stroke,we induced photochemical infarction of the sensorimotor cortex leading to Wallerian degeneration along the full extent of the corticospinal tract.We first used a routine,sensitive marker of axonal injury,amyloid precursor protein,to examine Wallerian degeneration of the corticospinal tract.An antibody to amyloid precursor protein mapped exclusively to proximal axonal segments within the ischemic cortex,with no positive signal in distal parts of the corticospinal tract,at all time points.To improve visualization of Wallerian degeneration,we next utilized an orthograde virus that expresses green fluorescent protein to label the corticospinal tract and then quantitatively evaluated green fluorescent protein-expressing axons.Using this approach,we found that axonal degeneration began on day 3 post-stroke and was almost complete by 7 days after stroke.In addition,microglia mobilized and activated early,from day 7 after stroke,but did not maintain a phagocytic state over time.Meanwhile,astrocytes showed relatively delayed mobilization and a moderate response to Wallerian degeneration.Moreover,no anterograde degeneration of spinal anterior horn cells was observed in response to Wallerian degeneration of the corticospinal tract.In conclusion,our data provide evidence for dynamic,pathogenic spatiotemporal changes in major cellular components of the corticospinal tract during Wallerian degeneration.

Passive activity enhances residual control ability in patients with complete spinal cord injury

Patients with complete spinal cord injury retain the potential for volitional muscle activity in muscles located below the spinal injury level.However,because of prolonged inactivity,initial attempts to activate these muscles may not effectively engage any of the remaining neurons in the descending pathway.A previous study unexpectedly found that a brief clinical round of passive activity significantly increased volitional muscle activation,as measured by surface electromyography.In this study,we further explored the effect of passive activity on surface electromyographic signals during volitional control tasks among individuals with complete spinal cord injury.Eleven patients with chronic complete thoracic spinal cord injury were recruited.Surface electromyography data from eight major leg muscles were acquired and compared before and after the passive activity protocol.The results indicated that the passive activity led to an increased number of activated volitional muscles and an increased frequency of activation.Although the cumulative root mean square of surface electromyography amplitude for volitional control of movement showed a slight increase after passive activity,the difference was not statistically significant.These findings suggest that brief passive activity may enhance the ability to initiate volitional muscle activity during surface electromyography tasks and underscore the potential of passive activity for improving residual motor control among patients with motor complete spinal cord injury.

Clinical and molecular significance of homologous recombination deficiency positive non-small cell lung cancer in Chinese population:An integrated genomic and transcriptional analysis

Objective:The clinical significance of homologous recombination deficiency(HRD)in breast cancer,ovarian cancer,and prostate cancer has been established,but the value of HRD in non-small cell lung cancer(NSCLC)has not been fully investigated.This study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical care.Methods:A total of 355 treatment-naïve NSCLC patients were retrospectively enrolled.HRD status was assessed using the AmoyDx Genomic Scar Score(GSS),with a score of≥50 considered HRD-positive.Genomic,transcriptomic,tumor microenvironmental characteristics and prognosis between HRD-positive and HRDnegative patients were analyzed.Results:Of the patients,25.1%(89/355)were HRD-positive.Compared to HRD-negative patients,HRDpositive patients had more somatic pathogenic homologous recombination repair(HRR)mutations,higher tumor mutation burden(TMB)(P<0.001),and fewer driver gene mutations(P<0.001).Furthermore,HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes,MET and MYC in epidermal growth factor receptor(EGFR)/anaplastic lymphoma kinase(ALK)mutant NSCLC,and more PIK3CA and AURKA in EGFR/ALK wild-type NSCLC.HRD-positive NSCLC displayed higher tumor proliferation and immunosuppression activity.HRD-negative NSCLC showed activated signatures of major histocompatibility complex(MHC)-II,interferon(IFN)-γand effector memory CD8+T cells.HRD-positive patients had a worse prognosis and shorter progressionfree survival(PFS)to targeted therapy(first-and third-generation EGFR-TKIs)(P=0.042).Additionally,HRDpositive,EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy regimens.Conclusions:Unique genomic and transcriptional characteristics were found in HRD-positive NSCLC.Poor prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive NSCLC.This study highlights potential actionable alterations in HRD-positive NSCLC,suggesting possible combinational therapeutic strategies for these patients.

BLOW-UP SOLUTIONS OF TWO-COUPLED NONLINEAR SCHR?DINGER EQUATIONS IN THE RADIAL CASE

We consider the blow-up solutions to the following coupled nonlinear Schr¨odinger equations{iu_(t)+Δu+(|u|^(2p)+|u|^(p−1)|v|^(p+1))u=0,iv_(t)+Δv+(|v|^(2p)+|v|^(p−1)|u|^(p+1))v=0,u(0,x)=u0(x),v(0,x)=v0(x),x 2 R N,t0.On the basis of the conservation of mass and energy,we establish two sufficient conditions to obtain the existence of a blow-up for radially symmetric solutions.These results improve the blow-up result of Li and Wu[10]by dropping the hypothesis of finite variance((|x|u_(0),|x|v_(0))∈ L^(2)(R^(N))×L^(2)(R^(N))).

Activation of endogenous neurogenesis and angiogenesis by basic fibroblast growth factor-chitosan gel in an adult rat model of ischemic stroke

Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain injury.However,whether bioactive materials can repair the damage caused by ischemic stroke by activating endogenous neurogenesis and angiogenesis is still unknown.In this study,we applied chitosan gel loaded with basic fibroblast growth factor to the stroke cavity 7 days after ischemic stroke in rats.The gel slowly released basic fibroblast growth factor,which improved the local microenvironment,activated endogenous neural stem/progenitor cells,and recruited these cells to migrate toward the penumbra and stroke cavity and subsequently differentiate into neurons,while enhancing angiogenesis in the penumbra and stroke cavity and ultimately leading to partial functional recovery.This study revealed the mechanism by which bioactive materials repair ischemic strokes,thus providing a new strategy for the clinical application of bioactive materials in the treatment of ischemic stroke.

The advantages of multi-level omics research on stem cell-based therapies for ischemic stroke

Stem cell transplantation is a potential therapeutic strategy for ischemic stroke. However, despite many years of preclinical research, the application of stem cells is still limited to the clinical trial stage. Although stem cell therapy can be highly beneficial in promoting functional recovery, the precise mechanisms of action that are responsible for this effect have yet to be fully elucidated. Omics analysis provides us with a new perspective to investigate the physiological mechanisms and multiple functions of stem cells in ischemic stroke. Transcriptomic, proteomic, and metabolomic analyses have become important tools for discovering biomarkers and analyzing molecular changes under pathological conditions. Omics analysis could help us to identify new pathways mediated by stem cells for the treatment of ischemic stroke via stem cell therapy, thereby facilitating the translation of stem cell therapies into clinical use. In this review, we summarize the pathophysiology of ischemic stroke and discuss recent progress in the development of stem cell therapies for the treatment of ischemic stroke by applying multi-level omics. We also discuss changes in RNAs, proteins, and metabolites in the cerebral tissues and body fluids under stroke conditions and following stem cell treatment, and summarize the regulatory factors that play a key role in stem cell therapy. The exploration of stem cell therapy at the molecular level will facilitate the clinical application of stem cells and provide new treatment possibilities for the complete recovery of neurological function in patients with ischemic stroke.

A core scientific problem in the treatment of central nervous system diseases:newborn neurons

It has long been asserted that failure to recover from central nervous system diseases is due to the system's intricate structure and the regenerative incapacity of adult neurons.Yet over recent decades,numerous studies have established that endogenous neurogenesis occurs in the adult central nervous system,including humans'.This has challenged the long-held scientific consensus that the number of adult neurons remains constant,and that new central nervous system neurons cannot be created or renewed.Herein,we present a comprehensive overview of the alterations and regulatory mechanisms of endogenous neurogenesis following central nervous system injury,and describe novel treatment strategies that to rget endogenous neurogenesis and newborn neurons in the treatment of central nervous system injury.Central nervous system injury frequently results in alterations of endogenous neurogenesis,encompassing the activation,proliferation,ectopic migration,diffe rentiation,and functional integration of endogenous neural stem cells.Because of the unfavorable local microenvironment,most activated neural stem cells diffe rentiate into glial cells rather than neurons.Consequently,the injury-induced endogenous neurogenesis response is inadequate for repairing impaired neural function.Scientists have attempted to enhance endogenous neurogenesis using various strategies,including using neurotrophic factors,bioactive materials,and cell reprogramming techniques.Used alone or in combination,these therapeutic strategies can promote targeted migration of neural stem cells to an injured area,ensure their survival and diffe rentiation into mature functional neurons,and facilitate their integration into the neural circuit.Thus can integration re plenish lost neurons after central nervous system injury,by improving the local microenvironment.By regulating each phase of endogenous neurogenesis,endogenous neural stem cells can be harnessed to promote effective regeneration of newborn neurons.This offers a novel approach for treating central nervous system injury.

Chitosan-based thermosensitive hydrogel with long-term release of murine nerve growth factor for neurotrophic keratopathy

Neurotrophic keratopathy is a persistent defect of the corneal epithelium,with or without stromal ulceration,due to corneal nerve deficiency caused by a variety of etiologies.The treatment options for neurotrophic keratopathy are limited.In this study,an ophthalmic solution was constructed from a chitosan-based thermosensitive hydrogel with long-term release of murine nerve growth factor(CTH-mNGF).Its effectiveness was evaluated in corneal denervation(CD)mice and patients with neurotrophic keratopathy.In the preclinical setting,CTH-mNGF was assessed in a murine corneal denervation model.CTH-mNGF was transparent,thermosensitive,and ensured sustained release of mNGF for over 20 hours on the ocular surface,maintaining the local mNGF concentration around 1300 pg/mL in vivo.Corneal denervation mice treated with CTH-mNGF for 10 days showed a significant increase in corneal nerve area and total corneal nerve length compared with non-treated and CTH treated mice.A subsequent clinical trial of CTH-mNGF was conducted in patients with stage 2 or 3 neurotrophic keratopathy.Patients received topical CTH-mNGF twice daily for 8 weeks.Fluorescein sodium images,Schirmer’s test,intraocular pressure,Cochet-Bonnet corneal perception test,and best corrected visual acuity were evaluated.In total,six patients(total of seven eyes)diagnosed with neurotrophic keratopathy were enrolled.After 8 weeks of CTH-mNGF treatment,all participants showed a decreased area of corneal epithelial defect,as stained by fluorescence.Overall,six out of seven eyes had fluorescence staining scores<5.Moreover,best corrected visual acuity,intraocular pressure,Schirmer’s test and Cochet-Bonnet corneal perception test results showed no significant improvement.An increase in corneal nerve density was observed by in vivo confocal microscopy after 8 weeks of CTH-mNGF treatment in three out of seven eyes.This study demonstrates that CTH-mNGF is transparent,thermosensitive,and has sustained-release properties.Its effectiveness in healing corneal epithelial defects in all eyes with neurotrophic keratopathy suggests CTH-mNGF has promising application prospects in the treatment of neurotrophic keratopathy,being convenient and cost effective.

Papillary serous carcinoma of the uterine cervix:a clinicopathological analysis of 4 cases and a literature review

Objective To investigate the clinicopathological characteristics and clinical treatment outcomes of patients with papillary serous carcinoma of the uterine cervix(PSCC).Methods In this study, 4 patients with histologically confirmed papillary serous carcinoma of the uterine cervix were retrospectively investigated. Pap smears, human papillomavirus(HPV) screening, tumor marker status, biopsy analysis, and relevant imaging examinations were conducted for the confirmation of primary diagnosis and recurrence. Patients underwent surgery, chemotherapy, or radiotherapy, and survival were the main endpoint.Results The 4 patients were diagnosed with IB1, IB1, IIA, or IIIB disease. Two patients(2/4) presented with recurrence within 18 months after primary therapy. Compared with chemotherapy alone(progressionfree survival(PFS): 11 months), radiotherapy combined with adjuvant chemotherapy showed favorable PFS rates(PFS: 20, 36, 13 months in 3 cases), although valid statistical analysis was not feasible because of the small sample size. The 5-year survival rate was 0%, and the 3-year survival rate was 75%. Our data, in agreement with the literature evidence, showed that the number of moderate-risk and high-risk factors in patients diagnosed with PSCC at an early stage was higher than that in patients diagnosed with common adenocarcinoma/squamous carcinoma of the uterine cervix.Conclusion PSCC has a poor clinical prognosis, and compared with chemotherapy alone, radiotherapy combined with adjuvant chemotherapy may lead to improved PFS.

Particle Velocity Sensor and Its Application in Near-Field Noise Scanning Measurement

The Particle Velocity Sensor (PVS) is a kind of acoustic transducer which measures the particle velocity directly with figure-of-eight directivity. This paper proposes a near-field noise scanning technology based on the research of PVS, pressure-particle velocity (P-U) probe, and its application in noise source identification. Firstly, the principle and characteristics of PVS are presented. Secondly, a P-U probe is designed on the basis of PVS development. Finally, the noise measurement experiment for a single source is arranged and conducted. The result shows that the proposed P-U probe performs well in near-field noise source identification and localization.

Adult Mammalian Neurogenesis:Hopes and Challenges in the Repair of Spinal Cord Injury

Adult endogenous neurogenesis was first defined as the generation of neurons and glia cells in the central nervous system(CNS);it was subsequently referred to as the activation of endogenous neural stem cells,and ultimately limited to the generation of new neurons[1].The research team led by Xiaoguang Li enriched this concept in 2015:Endogenous neural stem cells in the adult CNS can be activated,recruited,and migrated to the injured area,where these stem cells further differentiate into mature neurons.

Genome-wide development and utilization of Simple Sequence Repeats in Chinese cabbage(Brassica rapa L.ssp.pekinensis)

With the complementation of whole-genome sequencing of Chinese cabbage,it is necessary to develop genome-wide Simple Sequence Repeat(SSR)markers and analyse their characteristics,which will bring a revolution in the molecular marker-assisted breeding of Chinese cabbage.In this study distribution and characteristics of SSR loci in the genome of Chinese cabbage'Chiifu'was analyzed.Finally,a total of 173,892 SSR markers that occurred in 10 chromosomes were identified,and Perfect Repeat Motifs(P type)which is a main form of SSR loci with a mean distance of 1.89 kb/SSR was identified.Among them,mono-,di-,and tri-nucleotide repeat motifs were equally distributed across chromosomes compared with tetra-,penta-,and hexa-nucleotide repeat motifs.The largest proportion of SSR loci consisted of mono-and dinucleotide repeat motifs,which accounted for 93.04%of the total SSR loci.A/T and AT/TA were the most abundant motifs,accounting for 97.61%and 64.05%of the mono-and dinucleotide repeats,respectively.Furthermore,200 SSR markers were used for the amplification of 12 Chinese cabbage germplasm,in which 30 were highly polymorphic.These SSR markers were further used for the association analyses of flowering time of 190 Chinese cabbage accessions.The results revealed that 9 and 10 alleles were associated with bolting and flowering time,respectivley.The results show that development of SSR markers is feasible and useful in marker assisted selection of Chinese cabbage.

流动有用吗?——高学历者的教育失配与工作流动

伴随中国高等教育的扩招进程,教育失配现象已经在劳动力市场中屡见不鲜。但是,个体在职业生涯中的工作流动能否摆脱教育失配困境?学界对这一问题存在论争。本文聚焦高学历者的职业史,探索教育失配和工作流动的关系,并通过2021年“社会网络与职业经历”调查数据开展实证研究。研究发现:第一,初职岗位教育失配方面,单位体制、学历和性别是重要影响因素。第二,初职岗位的教育失配者,更有可能发生跳槽或外部流动。第三,跳槽或外部流动并不能有效摆脱现职教育失配,也难以提升劳动者的收入水平,而工作晋升则可以有效摆脱教育失配状态和提升收入水平。以上结论预示着,在教育失配者的职业生涯中,工作跳槽并不是摆脱教育失配的有效路径,而工作晋升在一定程度上可以促进教育匹配。

Upregulation of histone H3 caused by CRYAA may contribute to the development of age-related cataract

Objective:Age-relate cataract(ARC)is a disease of the eyes with no effective drugs to prevent or treat patients.The aim of the present study is to determine whether histone H3,αA-crystallin(CRYAA),β-galactosidase(GLB1),and p53 are involved in the pathogenesis of ARC.Methods:A total of 99 anterior lens capsules(ALCs)of patients with ARC of various nuclear grades,ultraviolet models of ALCs,and two human lens epithelial cell lines(FHL-124 and SRA01/04)were used,and the expression of histone H3,CRYAA,GLB1,and p53 were detected by immunoblotting and reverse transcription and real time-quantitative polymerase chain reaction.The association between CRYAA with histone H3,GLB1,and p53 was assessed in FHL-124 and SRA01/04 cells following CRYAA overexpression.Results:Histone H3 and p53 in ALCs of patients with ARC were up-regulated in a grade-dependent manner,and the expression of CRYAA showed a positive association with histone H3,p53,and GLB1.In UV models of ALCs and human lens epithelial cell lines,the expression levels of histone H3,cell apoptosis factors(Bax/Bcl-2,cleaved caspase-3),and inflammation factors(interleukin-6,tumor necrosis factor-α)were all up-regulated.Furthermore,transfection of CRYAA in FHL-124 cells induced overexpression of histone H3.Conclusion:CRYAA-mediated upregulation of histone H3 may be involved in the pathogenesis of ARC.p53 may also have a role in ARC development,but not via the CRYAA-histone H3 axis.The results of the present study may assist in improving our understanding of the pathogenesis of ARC and in identifying potential targets for treatment.

影像引导射频消融治疗肺部肿瘤专家共识(2018年版)

1概述肺癌是最常见的恶性肿瘤之一,在世界各地,肺癌均居恶性肿瘤死亡构成比的第一位,其发病率和死亡率仍在不断升高。据世界卫生组织（World Health Organization,WHO）下属的国际癌症研究机构（International Agency for Research on Cancer,IARC）出版的GLOBOCAN 2012估计：全世界肺癌新发病例1 8 2.5万（男性124.2万,女性58.3万）.

热消融治疗肺部亚实性结节专家共识(2021年版)

局部热消融技术在肺部结节治疗领域正处在起步与发展阶段,为了肺结节热消融治疗的临床实践和规范发展,由"中国医师协会肿瘤消融治疗技术专家组""中国医师协会介入医师分会肿瘤消融专业委员会""中国抗癌协会肿瘤消融治疗专业委员会""中国临床肿瘤学会消融专家委员会"组织多学科国内有关专家,讨论制定了"热消融治疗肺部亚实性结节专家共识(2021年版)"。主要内容包括:(1)肺部亚实性结节的临床评估;(2)热消融治疗肺部亚实性结节技术操作规程、适应证、禁忌证、疗效评价和相关并发症;(3)存在的问题和未来发展方向。

Durably and intrinsically antibacterial polyamide 6(PA6)via backbone end-capping with high temperature-resistant imidazolium

The antibacterial polyamide 6(PA6)material has attracted great research interest due to its wide ap-plication in food packaging,biomedical fields,functional textiles,and other fields.However,it is still a challenge to prepare intrinsically antibacterial PA6 with highly efficient and durably antibacterial activity via polymerization.Herein,the antibacterial imidazolium ionic liquid of 3-carboxymethyl-1-decyl imida-zole chloride was designed and synthesized for adapting the polymerization and processing temperature of PA6.Then antibacterial PA6(PA6-IL)was synthesized through hydrolyzed ring-opening copolymeriza-tion with imidazolium at the end of the backbones.Compared to physical blending or post-modification methods,antibacterial agents as end-capping reagents of polymer backbones endowed PA6 with intrin-sic antibacterial activity.As expected,the obtained PA6-IL exhibited not just comparable physicochemical and mechanical properties to conventional PA6 but excellent antibacterial activity of low antibacterial time to 60 min and durability for 28 days.Additionally,the corresponding electrospun PA6-IL nanofi-brous membranes showed homogenous morphology and remarkable hydrophilicity of 7.7° as well as the high-efficient antibacterial activity.Melt-spun PA6-IL microfibers revealed a smooth surface as well as enhanced tensile strength and increased breaking elongation compared to those of conventional PA6.The PA6-IL microfibers also behaved with excellent antibacterial efficiency and durability.Accordingly,this work provides a feasible and straightforward strategy to prepare durably and intrinsically antibacterial PA6 materials especially PA6 fibers,which can be widely applied in the textiles field.

Genesis of sandstone-type uranium deposits along the northern margin of the Ordos Basin,China

Sandstone-type U mineral resources are among the important sources for nuclear energy.The U deposits in the Ordos Basin in China form part of the northern segment of the sandstone-hosted Central Asian Uranium MegaProvince.Two types of mineralizations are recognized in this basin:"phreatic permeable type"and"interlayer permeable type",both exhibiting features equivalent to roll-front subtypes.The"interlayer permeable type"is widely accepted as the dominant mineralization type for sandstone-type uranium deposits within large-scale basins,also designated as the"interlayer oxidation zone type",based on the horizontal color zoning model representing changing redox conditions.Here we synthesize data from several drill holes within the Ordos Basin,which suggest that major Mesozoic tectonic movements controlled the evolution of the sedimentary system in the basin.These tectonic movements contributed to the formation of three angular unconformities and four parallel unconformities as inferred from the stratigraphic relationships.In addition,other features such as vertical color zoning,paleo-channel controlled tabular or lentoid ore bodies(without roll-type)and a group interlayer horizontal zoning of altered minerals are also documented.Sequence stratigraphic analysis indicates that the Ordos Basin generally witnessed four cycles of water level variations during Mesozoic.During the variations,three high water level and three low water level events were recorded.Biological characteristics imply that the Ordos Basin went through multiple arid to humid climatic evolutions during Mesozoic.Combining the newly documented features with some novel concepts on the hydrodynamic mechanism for supergene ore-forming fluids,we propose a metallogenic model which invokes the importance of tectonic movements and water level fluctuations to explain the genesis of uranium deposits along the northern margin of the Ordos Basin.

Laser cleaning of steel structure surface for paint removal and repaint adhesion

Paint removal from steel structure is executed for shipyards of marine and offshore engineering.Due to environmental unfriendliness and unhealthy drawbacks of sand blasting technique, laser ablation technique is proposed as a substituting method.By absorbing high energy of the 1064 nm pulsed laser, the paint is vaporized quickly.The ablated debris is then collected by using a suction pump.Initial metal surface of the steel is exposed when laser beam irradiates perpendicularly and scans over it.The cleaned surface fulfills the requirements of surface preparation standards ISO 8501 of SA2.The adhesion is further characterized with pull-off test after carrying out painting with Jotamastic 87 aluminum paint.The repainting can be embedded onto the laser cleaned surface to bond much more tightly.The excellent adhesion strength of 20 MPa between repainted coating and the substrate is achieved, which is higher than what is required by shipyards applications.

过度教育的动态变迁与收入轨迹——基于CFPS2010-2018数据的实证分析

过度教育的动态变迁和收入轨迹是教育匹配领域的重要议题,但以往文献很少将二者联合起来进行动态考察。聚焦中国城镇劳动力市场,使用2010-2018年中国家庭追踪调查数据,分析过度教育在动态变迁中的收入轨迹。研究发现:第一,序列分析结果表明,过度教育在个体职业生涯中更有可能是一种持续性现象。第二,通过使用固定效应模型,控制以个人能力为代表的、不可观测且不随时间变化的因素之后,发现过度教育者的确比同等教育程度的适度教育者拥有更低的收入水平。第三,不同教育匹配轨迹中的个体收入增长曲线表明,持续适度教育者平均收入最高,持续过度教育者平均收入水平则最低,那些摆脱过度教育的个体会实现收入的迅速增长,而陷入过度教育则收入增长明显减缓甚至出现下降。这些结论有助于理解过度教育的变迁趋势及其收入效应,从教育系统、用人单位以及劳动力市场出发,提出了政策建议。