Meningeal lymphatic vessel crosstalk with central nervous system immune cells in aging and neurodegenerative diseases

Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.

Differential distribution of PINK1 and Parkin in the primate brain implies distinct roles

The vast majority of in vitro studies have demonstrated that PINK1 phosphorylates Parkin to work together in mitophagy to protect against neuronal degeneration.However,it remains largely unclear how PINK1 and Parkin are expressed in mammalian brains.This has been difficult to address because of the intrinsically low levels of PINK1 and undetectable levels of phosphorylated Parkin in small animals.Understanding this issue is critical for elucidating the in vivo roles of PINK1 and Parkin.Recently,we showed that the PINK1 kinase is selectively expressed as a truncated form(PINK1–55)in the primate brain.In the present study,we used multiple antibodies,including our recently developed monoclonal anti-PINK1,to validate the selective expression of PINK1 in the primate brain.We found that PINK1 was stably expressed in the monkey brain at postnatal and adulthood stages,which is consistent with the findings that depleting PINK1 can cause neuronal loss in developing and adult monkey brains.PINK1 was enriched in the membrane-bound fractionations,whereas Parkin was soluble with a distinguishable distribution.Immunofluorescent double staining experiments showed that PINK1 and Parkin did not colocalize under physiological conditions in cultured monkey astrocytes,though they did colocalize on mitochondria when the cells were exposed to mitochondrial stress.These findings suggest that PINK1 and Parkin may have distinct roles beyond their well-known function in mitophagy during mitochondrial damage.

A Left-Handed, Stem-Twining Plant from the Miocene Shanwang Formation of Eastern China

Twining stems of plants are very common in extant tropical and subtropical forests, and the climbing growth habit of plants may be an evolutionary innovation and ecological adaptation to either closed, shady or open, edge environments. However, the origin of handedness in climbing plants remains unclear. Here we report a Miocene (ca. 16 million years ago) macrofossil from the Shanwang Formation of Shandong Province, Eastern China, unequivocally exhibiting the first direct fossil evidence for a left-handed, stem-twining growth habit in plants. This fossil plant bears a thicker, slightly curved supporting stem (2 - 3.5 mm wide), which is loosely, spirally twined by a thinner stem (1.5 - 2 mm wide), possibly representing part of distal branches from a liana or vine.

Ti、Zr和Hf元素协同优化Nb-Si基合金显微组织、相组成和室温断裂韧性

采用真空电弧熔炼制备Nb-16Si-xTi-yZr-zHf (x=18, 22;y=0, 4;z=0, 4;摩尔分数,%)合金并研究Ti、Zr与Hf元素对Nb-Si合金物相组成、显微组织、断裂韧性以及裂纹扩展行为的影响。结果表明:单独添加4%Zr元素能促进(Nb,X)3Si向Nb固溶体(Nbss)/γ-(Nb,X)5Si3共析反应的发生;同时添加Ti、Zr、Hf元素能进一步促进共析反应的发生。裂纹倾向于在(Nb,X)3Si中扩展,当裂纹途径Nb固溶体时会发生偏转。细密的Nbss/γ-(Nb,X)5Si3共晶组织以及层状Nbss/γ-(Nb,X)5Si3共晶组织可以使裂纹产生桥接与分支,阻碍裂纹的扩展。Nb-16Si-22Ti-4Zr-4Hf的合金化元素含量最高,因此,其室温断裂韧性最好(11.62 MPa·m1/2),相较于Nb-16Si-18Ti提高87.7%,性能的提升主要归因于存在层状共晶组织。

Drilling-based measuring method for the c-φ parameter of rock and its field application

The technology of drilling tests makes it possible to obtain the strength parameter of rock accurately in situ. In this paper, a new rock cutting analysis model that considers the influence of the rock crushing zone(RCZ) is built. The formula for an ultimate cutting force is established based on the limit equilibrium principle. The relationship between digital drilling parameters(DDP) and the c-φ parameter(DDP-cφ formula, where c refers to the cohesion and φ refers to the internal friction angle) is derived, and the response of drilling parameters and cutting ratio to the strength parameters is analyzed. The drillingbased measuring method for the c-φ parameter of rock is constructed. The laboratory verification test is then completed, and the difference in results between the drilling test and the compression test is less than 6%. On this basis, in-situ rock drilling tests in a traffic tunnel and a coal mine roadway are carried out, and the strength parameters of the surrounding rock are effectively tested. The average difference ratio of the results is less than 11%, which verifies the effectiveness of the proposed method for obtaining the strength parameters based on digital drilling. This study provides methodological support for field testing of rock strength parameters.

Comparative analysis of primate and pig cells reveals primate-specific PINK1 expression and phosphorylation

PTEN-induced putative kinase 1(PINK1),a mitochondrial kinase that phosphorylates Parkin and other proteins,plays a crucial role in mitophagy and protection against neurodegeneration.Mutations in PINK1 and Parkin can lead to loss of function and early onset Parkinson's disease.However,there is a lack of strong in vivo evidence in rodent models to support the theory that loss of PINK1 affects mitophagy and induces neurodegeneration.Additionally,PINK1 knockout pigs(Sus scrofa)do not appear to exhibit neurodegeneration.In our recent work involving non-human primates,we found that PINK1 is selectively expressed in primate brains,while absent in rodent brains.To extend this to other species,we used multiple antibodies to examine the expression of PINK1 in pig tissues.In contrast to tissues from cynomolgus monkeys(Macaca fascicularis),our data did not convincingly demonstrate detectable PINK1expression in pig tissues.Knockdown of PINK1 in cultured pig cells did not result in altered Parkin and BAD phosphorylation,as observed in cultured monkey cells.A comparison of monkey and pig striatum revealed more PINK1-phosphorylated substrates in the monkey brain.Consistently,PINK1 knockout in pigs did not lead to obvious changes in the phosphorylation of Parkin and BAD.These findings provide new evidence that PINK1expression is specific to primates,underscoring the importance of non-human primates in investigating PINK1function and pathology related to PINK1 deficiency.

Method for evaluation of geological strength index of carbonate cliff rocks:Coupled hyperspectral-digital borehole image technique

The deterioration of unstable rock mass raised interest in evaluating rock mass quality.However,the traditional evaluation method for the geological strength index(GSI)primarily emphasizes the rock structure and characteristics of discontinuities.It ignores the influence of mineral composition and shows a deficiency in assessing the integrity coefficient.In this context,hyperspectral imaging and digital panoramic borehole camera technologies are applied to analyze the mineral content and integrity of rock mass.Based on the carbonate mineral content and fissure area ratio,the strength reduction factor and integrity coefficient are calculated to improve the GSI evaluation method.According to the results of mineral classification and fissure identification,the strength reduction factor and integrity coefficient increase with the depth of rock mass.The rock mass GSI calculated by the improved method is mainly concentrated between 40 and 60,which is close to the calculation results of the traditional method.The GSI error rates obtained by the two methods are mostly less than 10%,indicating the rationality of the hyperspectral-digital borehole image coupled evaluation method.Moreover,the sensitivity of the fissure area ratio(Sr)to GSI is greater than that of the strength reduction factor(a),which means the proposed GSI is suitable for rocks with significant fissure development.The improved method reduces the influence of subjective factors and provides a reliable index for the deterioration evaluation of rock mass.

Research advances in smart responsive-hydrogel dressings with potential clinical diabetic wound healing properties

The treatment of chronic and non-healing wounds in diabetic patients remains a major medical problem.Recent reports have shown that hydrogel wound dressings might be an effective strategy for treating diabetic wounds due to their excellent hydrophilicity,good drug-loading ability and sustained drug release properties.As a typical example,hyaluronic acid dressing(Healoderm)has been demonstrated in clinical trials to improve wound-healing efficiency and healing rates for diabetic foot ulcers.However,the drug release and degradation behavior of clinically-used hydrogel wound dressings cannot be adjusted according to the wound microenvironment.Due to the intricacy of diabetic wounds,antibiotics and other medications are frequently combined with hydrogel dressings in clinical practice,although these medications are easily hindered by the hostile environment.In this case,scientists have created responsive-hydrogel dressings based on the microenvironment features of diabetic wounds(such as high glucose and low pH)or combined with external stimuli(such as light or magnetic field)to achieve controllable drug release,gel degradation,and microenvironment improvements in order to overcome these clinical issues.These responsive-hydrogel dressings are anticipated to play a significant role in diabetic therapeutic wound dressings.Here,we review recent advances on responsive-hydrogel dressings towards diabetic wound healing,with focus on hydrogel structure design,the principle of responsiveness,and the behavior of degradation.Last but not least,the advantages and limitations of these responsive-hydrogels in clinical applications will also be discussed.We hope that this review will contribute to furthering progress on hydrogels as an improved dressing for diabetic wound healing and practical clinical application.

Host-induced gene silencing of the Verticillium dahliae thiamine transporter protein gene(VdThit)confers resistance to Verticillium wilt in cotton

Verticillium wilt(VW),induced by the soil-borne fungus Verticillium dahliae(Vd),poses a substantial threat to a diverse array of plant species.Employing molecular breeding technology for the development of cotton varieties with heightened resistance to VW stands out as one of the most efficacious protective measures.In this study,we successfully generated two stable transgenic lines of cotton(Gossypium hirsutum L.),VdThitRNAi-1 and VdThit-RNAi-2,using host-induced gene silencing(HIGS)technology to introduce double-stranded RNA(dsRNA)targeting the thiamine transporter protein gene(VdThit).Southern blot analysis confirmed the presence of a single-copy insertion in each line.Microscopic examination showed marked reductions in the colonization and spread of Vd-mCherry in the roots of VdThit-RNAi cotton compared to wild type(WT).The corresponding disease index and fungal biomass of VdThit-RNAi-1/2 also exhibited significant reductions.Real-time quantitative PCR(qRT-PCR)analysis demonstrated a substantial inhibition of VdThit expression following prolonged inoculation of VdThit-RNAi cotton.Small RNA sequencing(sRNA-Seq)analysis revealed the generation of a substantial number of VdThit-specific siRNAs in the VdThit-RNAi transgenic lines.Additionally,the silencing of VdThit by the siVdThit produced by VdThit-RNAi-1/2 resulted in the elevated expression of multiple genes involved in the thiamine biosynthesis pathway in Vd.Under field conditions,VdThit-RNAi transgenic cotton exhibited significantly enhanced disease resistance and yield compared with WT.In summary,our findings underscore the efficacy of HIGS targeting VdThit in restraining the infection and spread of Vd in cotton,thereby potentially enabling the development of cotton breeding as a promising strategy for managing VW.

FibroScan-aspartate transaminase:A superior non-invasive model for diagnosing high-risk metabolic dysfunction-associated steatohepatitis

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)with hepatic histological NAFLD activity score≥4 and fibrosis stage F≥2 is regarded as“at risk”non-alcoholic steatohepatitis(NASH).Based on an international consensus,NAFLD and NASH were renamed as metabolic dysfunction-associated steatotic liver disease(MASLD)and metabolic dysfunction-associated steatohepatitis(MASH),respectively;hence,we introduced the term“high-risk MASH”.Diagnostic values of seven non-invasive models,including FibroScan-aspartate transaminase(FAST),fibrosis-4(FIB-4),aspartate transaminase to platelet ratio index(APRI),etc.for high-risk MASH have rarely been studied and compared in MASLD.AIM To assess the clinical value of seven non-invasive models as alternatives to liver biopsy for diagnosing high-risk MASH.METHODS A retrospective analysis was conducted on 309 patients diagnosed with NAFLD via liver biopsy at Beijing Ditan Hospital,between January 2012 and December 2020.After screening for MASLD and the exclusion criteria,279 patients wereincluded and categorized into high-risk and non-high-risk MASH groups.Utilizing threshold values of each model,sensitivity,specificity,positive predictive value(PPV),and negative predictive values(NPV),were calculated.Receiver operating characteristic curves were constructed to evaluate their diagnostic efficacy based on the area under the curve(AUROC).RESULTS MASLD diagnostic criteria were met by 99.4%patients with NAFLD.The MASLD population was analyzed in two cohorts:Overall population(279 patients)and the subgroup(117 patients)who underwent liver transient elastography(FibroScan).In the overall population,FIB-4 showed better diagnostic efficacy and higher PPV,with sensitivity,specificity,PPV,NPV,and AUROC of 26.9%,95.2%,73.5%,72.2%,and 0.75.APRI,Forns index,and aspartate transaminase to alanine transaminase ratio(ARR)showed moderate diagnostic efficacy,whereas S index and gamma-glutamyl transpeptidase to platelet ratio(GPR)were relatively weaker.In the subgroup,FAST had the highest diagnostic efficacy,its sensitivity,specificity,PPV,NPV,and AUROC were 44.2%,92.3%,82.1%,67.4%,and 0.82.The FIB-4 AUROC was 0.76.S index and GPR exhibited almost no diagnostic value for high-risk MASH.CONCLUSION FAST and FIB-4 could replace liver biopsy as more effectively diagnostic methods for high-risk MASH compared to APRI,Forns index,ARR,S index,and GPR;FAST is superior to FIB-4.

氢燃料电池用气浮离心空压机实验与模拟研究

气浮轴承离心空压机具有无油、高效、低成本、轻量化和动态响应性好等优点,已成为车载氢燃料电池空压机的最佳选择。本文介绍了自主研发的额定压比2.8、质量流量130g/s、转速88000r/min、功率22kW的两级气浮轴承离心空压机,用于匹配电堆功率130kW的车载氢燃料电池。在离心空压机气动性能试验台上测试了空压机在60000~95000r/min范围内的气动性能,同时构建了离心空压机的泄漏通流模型并对其进行了数值模拟,最后将模拟结果与实验数据进行了对比分析。研究结果表明,该离心空压机在实验时最大转速达95000r/min,最大绝热效率可达77.04%。

社会信任与家庭金融科技使用

信任是金融交易的基础,金融科技作为新金融形态往往更需要信任。本文基于中国家庭金融调查(CHFS)2017年数据,利用手机银行(网上银行)、互联网理财、互联网借贷和移动支付四个维度衡量家庭金融科技使用,研究了社会信任对家庭金融科技使用的影响。研究发现,社会信任水平的提升显著促进了家庭使用各类金融科技服务的概率,这一结果在考虑了内生性问题情况下依然稳健。由于受到传统观念影响、学习能力偏弱等原因,老年人口和低教育水平人口往往是数字技术使用的弱势群体。本文的异质性分析发现,社会信任对这些群体的金融科技使用影响更为重要。本文的研究表明,社会信任水平对家庭金融科技使用率具有重要的作用。加强社会信任建设,对促进金融科技使用、缩小数字鸿沟以及实现普惠金融发展具有重要意义。

探索跨越时空的元素

古往今来,人们从未停止对物质与生命的探索,小到尘埃,大到宇宙。经过探索,人们发现这纷繁复杂的世界,目前已知竟由118种化学元素排列与组合构筑而成。作为构成万物的基元,元素所蕴含的秘密,是怎么被揭晓的?本文将从元素起源,元素认知历程以及元素应用历程等角度逐步揭开元素在不同时期的神秘面纱。

关于“智能化工”背景下物理化学教学改革的思考

在当前“智能化工”迅速发展的大背景下,作为化工专业的核心课程之一,物理化学的教学不仅要因应智能化工的发展对化工专业人才的知识和能力需求,同时也应积极探索教学方法和手段的创新,吸收智能化工发展的最新技术成果并应用于教学过程中。通过对课程体系内容的进一步优化、引入先进的计算机辅助教学以及模拟实验手段等,提升教学效果,增强学生的实践能力和创新意识,培养他们适应智能化工发展的能力。

Shear mechanical properties and fracturing responses of layered rough jointed rock-like materials

This study aims to investigate mechanical properties and failure mechanisms of layered rock with rough joint surfaces under direct shear loading.Cubic layered samples with dimensions of 100 mm×100 mm×100 mm were casted using rock-like materials,with anisotropic angle(α)and joint roughness coefficient(JRC)ranging from 15°to 75°and 2-20,respectively.The direct shear tests were conducted under the application of initial normal stress(σ_(n)) ranging from 1-4 MPa.The test results indicate significant differences in mechanical properties,acoustic emission(AE)responses,maximum principal strain fields,and ultimate failure modes of layered samples under different test conditions.The peak stress increases with the increasingαand achieves a maximum value atα=60°or 75°.As σ_(n) increases,the peak stress shows an increasing trend,with correlation coefficients R² ranging from 0.918 to 0.995 for the linear least squares fitting.As JRC increases from 2-4 to 18-20,the cohesion increases by 86.32%whenα=15°,while the cohesion decreases by 27.93%whenα=75°.The differences in roughness characteristics of shear failure surface induced byαresult in anisotropic post-peak AE responses,which is characterized by active AE signals whenαis small and quiet AE signals for a largeα.For a given JRC=6-8 andσ_(n)=1 MPa,asαincreases,the accumulative AE counts increase by 224.31%(αincreased from 15°to 60°),and then decrease by 14.68%(αincreased from 60°to 75°).The shear failure surface is formed along the weak interlayer whenα=15°and penetrates the layered matrix whenα=60°.Whenα=15°,as σ_(n) increases,the adjacent weak interlayer induces a change in the direction of tensile cracks propagation,resulting in a stepped pattern of cracks distribution.The increase in JRC intensifies roughness characteristics of shear failure surface for a smallα,however,it is not pronounced for a largeα.The findings will contribute to a better understanding of the mechanical responses and failure mechanisms of the layered rocks subjected to shear loads.

Gabapentinoids for the treatment of stroke

Gabapentinoid drugs(pregabalin and gabapentin) have been successfully used in the treatment of neuro pathic pain and in focal seizure prevention.Recent research has demonstrated their potent activities in modulating neurotransmitter release in neuronal tissue,oxidative stress,and inflammation,which matches the mechanism of action via voltage-gated calcium channels.In this review,we briefly elaborate on the medicinal history and ligand-binding sites of gabapentinoids.We systematically summarize the preclinical and clinical research on gabapentinoids in stroke,including ischemic stro ke,intracerebral hemorrhage,subarachnoid hemorrhage,seizures after stro ke,cortical spreading depolarization after stroke,pain after stroke,and nerve regeneration after stro ke.This review also discusses the potential to rgets of gabapentinoids in stroke;however,the existing results are still unce rtain regarding the effect of gabapentinoids on stroke and related diseases.Further preclinical and clinical trials are needed to test the therapeutic potential of gabapentinoids in stroke.Therefore,gabapentinoids have both opportunities and challenges in the treatment of stroke.

Variations and determinants of tissue carbon concentration of 32 sympatric temperate tree species

Plant carbon(C)concentration is a fundamental trait for estimating C storage and nutrient utilization.However,the mechanisms of C concentration variations among different tree tissues and across species remains poorly understood.In this study,we explored the variations and determinants of C concentration of nine tissues from 216 individuals of 32 tree species,with particular attention on the effect of wood porosity(i.e.,non-porous wood,diffuse-porous wood,and ring-porous wood).The inter-tissue pattern of C concentration diverged across the three porosity types;metabolically active tissues(foliage and fine roots,except for the foliage of ring-porous species)generally had higher C levels compared with inactive wood.The poor inter-correlations between tissue C concentrations indicated a necessity of measuring tissue-and specific-C concentrations.Carbon concentration for almost all tissues generally decreased from non-porous,to diffuse-porous and to ring-porous.Tissue C was often positively correlated with tissue(foliage and wood)density and tree size,while negatively correlated with growth rate,depending on wood porosity.Our results highlight the mediating effect of type of wood porosity on the variation in tissue C among temperate species.The variations among tissues were more important than that among species.These findings provided insights on tissue C concentration variability of temperate forest species.

Degradation analysis and doping modification optimization for high-voltage P-type layered cathode in sodium-ion batteries

Advancing high-voltage stability of layered sodium-ion oxides represents a pivotal avenue for their progress in energy storage applications.Despite this,a comprehensive understanding of the mechanisms underpinning their structural deterioration at elevated voltages remains insufficiently explored.In this study,we unveil a layer delamination phenomenon of Na_(0.67)Ni_(0.3)Mn_(0.7)O_(2)(NNM)within the 2.0-4.3 V voltage,attributed to considerable volumetric fluctuations along the c-axis and lattice oxygen reactions induced by the simultaneous Ni^(3+)/Ni^(4+)and anion redox reactions.By introducing Mg doping to diminished Ni-O antibonding,the anion oxidation-reduction reactions are effectively mitigated,and the structural integrity of the P2 phase remains firmly intact,safeguarding active sites and precluding the formation of novel interfaces.The Na_(0.67)Mg_(0.05)Ni_(0.25)Mn_(0.7)O_(2)(NMNM-5)exhibits a specific capacity of100.7 mA h g^(-1),signifying an 83%improvement compared to the NNM material within the voltage of2.0-4.3 V.This investigation underscores the intricate interplay between high-voltage stability and structural degradation mechanisms in layered sodium-ion oxides.

Testing method of rock structural plane using digital drilling

The rock mass consists of rock blocks and structural planes,which can reduce its integrity and strength.Therefore,accurately obtaining the characteristics of the rock mass structural plane is a prerequisite for evaluating stability and designing supports in underground engineering.Currently,there are no effective testing methods for the characteristic parameters of the rock mass structural plane in underground engineering.The paper presents the digital drilling technology as a new testing method of rock mass structural planes.Flawed rock specimens with cracks of varying widths and angles were used to simulate the rock mass structural planes,and the multifunctional rock mass digital drilling test system was employed to carry out the digital drilling tests.The analysis focuses on the variation laws of drilling parameters,such as drilling pressure and drilling torque,affected by the characteristics of prefabricated cracks,and clarifies the degradation mechanism of rock equivalent compressive strength.Additionally,an identification model for the characteristic parameters of rock mass structural planes during drilling is established.The test results indicate that the average difference of the characteristics of prefabricated cracks identified by the equivalent compressive strength is 2.45°and 0.82 mm,respectively.The identification model while drilling is verified to be correct due to the high identification accuracy.Based on this,a method for testing the characteristic parameters of the surrounding rock structural plane while drilling is proposed.The research offers a theoretical and methodological foundation for precise in situ identification of structural planes of the surrounding rock in underground engineering.

Myotis bat STING attenuates aging-related inflammation in female mice

Bats,notable as the only flying mammals,serve as natural reservoir hosts for various highly pathogenic viruses in humans(e.g.,SARS-CoV and Ebola virus).Furthermore,bats exhibit an unparalleled longevity among mammals relative to their size,particularly the Myotis bats,which can live up to 40 years.However,the mechanisms underlying these distinctive traits remain incompletely understood.In our prior research,we demonstrated that bats exhibit dampened STING-interferon activation,potentially conferring upon them the capacity to mitigate virus-or aging-induced inflammation.To substantiate this hypothesis,we established the first in vivo bat-mouse model for aging studies by integrating Myotis davidii bat STING(MdSTING)into the mouse genome.We monitored the genotypes of these mice and performed a longitudinal comparative transcriptomic analysis on MdSTING and wild-type mice over a 3-year aging process.Blood transcriptomic analysis indicated a reduction in aging-related inflammation in female MdSTING mice,as evidenced by significantly lower levels of pro-inflammatory cytokines and chemokines,immunopathology,and neutrophil recruitment in aged female MdSTING mice compared to aged wild-type mice in vivo.These results indicated that MdSTING knock-in attenuates the aging-related inflammatory response and may also improve the healthspan in mice in a sex-dependent manner.Although the underlying mechanism awaits further study,this research has critical implications for bat longevity research,potentially contributing to our comprehension of healthy aging in humans.