Porcine enteric alphacoronavirus infection increases lipid droplet accumulation to facilitate the virus replication

Coronaviruses are widely transmissible between humans and animals, causing diseases of varying severity. Porcine enteric alphacoronavirus(PEAV) is a newly-discovered pathogenic porcine enteric coronavirus in recent years, which causes watery diarrhea in newborn piglets. The host inflammatory responses to PEAV and its metabolic regulation mechanisms remain unclear, and no antiviral studies have been reported. Therefore, we investigated the pathogenic mechanism and antiviral drugs of PEAV. The transcriptomic analysis of PEAV-infected host cells revealed that PEAV could upregulate lipid metabolism pathways. In lipid metabolism, steady-state energy processes, which can be mediated by lipid droplets(LDs), are the main functions of organelles. LDs are also important in viral infection and inflammation. In infected cells, PEAV increased LD accumulation, upregulated NF-κB signaling, promoted the production of the inflammatory cytokines IL-1β and IL-8, and induced cell death. Inhibiting LD accumulation with a DGAT-1 inhibitor significantly inhibited PEAV replication, downregulated the NF-κB signaling pathway, reduced the production of IL-1β and IL-8, and inhibited cell death. The NF-κB signaling pathway inhibitor BAY11-7082 significantly inhibited LD accumulation and PEAV replication. Metformin hydrochloride also exerted anti-PEAV effects and significantly inhibited LD accumulation, downregulated the NF-κB signaling pathway, reduced the production of IL-1β and IL-8, and inhibited cell death. LD accumulation in the lipid metabolism pathway therefore plays an important role in the replication and pathogenesis of PEAV, and metformin hydrochloride inhibits LD accumulation and the inflammatory response to exert anti-PEAV activity and reducing pathological injury. These findings contribute new targets for developing treatments for PEAV infections.

Application of deep learning methods combined with physical background in wide field of view imaging atmospheric Cherenkov telescopes

The High Altitude Detection of Astronomical Radiation(HADAR)experiment,which was constructed in Tibet,China,combines the wide-angle advantages of traditional EAS array detectors with the high-sensitivity advantages of focused Cherenkov detectors.Its objective is to observe transient sources such as gamma-ray bursts and the counterparts of gravitational waves.This study aims to utilize the latest AI technology to enhance the sensitivity of HADAR experiments.Training datasets and models with distinctive creativity were constructed by incorporating the relevant physical theories for various applications.These models can determine the type,energy,and direction of the incident particles after careful design.We obtained a background identification accuracy of 98.6%,a relative energy reconstruction error of 10.0%,and an angular resolution of 0.22°in a test dataset at 10 TeV.These findings demonstrate the significant potential for enhancing the precision and dependability of detector data analysis in astrophysical research.By using deep learning techniques,the HADAR experiment’s observational sensitivity to the Crab Nebula has surpassed that of MAGIC and H.E.S.S.at energies below 0.5 TeV and remains competitive with conventional narrow-field Cherenkov telescopes at higher energies.In addition,our experiment offers a new approach for dealing with strongly connected,scattered data.

Thermally-induced cracking behaviors of coal reservoirs subjected to cryogenic liquid nitrogen shock

The benefits of using cryogenic liquid nitrogen shock to enhance coal permeability have been confirmed from experimental perspectives.In this paper,we develop a fully coupled thermo-elastic model in combination with the strain-based isotropic damage theory to uncover the cooling-dominated cracking behaviors through three typical cases,i.e.coal reservoirs containing a wellbore,a primary fracture,and a natural fracture network,respectively.The progressive cracking processes,from thermal fracture initiation,propagation or cessation,deflection,bifurcation to multi-fracture interactions,can be well captured by the numerical model.It is observed that two hierarchical levels of thermal fractures are formed,in which the number of shorter thermal fractures consistently exceeds that of the longer ones.The effects of coal properties related to thermal stress levels and thermal diffusivity on the fracture morphology are quantified by the fracture fractal dimension and the statistical fracture number.The induced fracture morphology is most sensitive to changes in the elastic modulus and thermal expansion coefficient,both of which dominate the complexity of the fracture networks.Coal reservoir candidates with preferred thermal-mechanical properties are also recommended for improving the stimulation effect.Further findings are that there exists a critical injection temperature and a critical in-situ stress difference,above which no thermal fractures would be formed.Preexisting natural fractures with higher density and preferred orientations are also essential for the formation of complex fracture networks.The obtained results can provide some theoretical support for cryogenic fracturing design in coal reservoirs.

Gamma/Hadron Separation Method for the HADAR Experiment

Ground-based arrays of imaging atmospheric Cherenkov telescopes(IACTs)are the most sensitiveγ-ray detectors for energies of approximately 100 Ge V and above.One such IACT is the High Altitude Detection of Astronomical Radiation(HADAR)experiment,which uses a large aperture refractive water lens system to capture atmospheric Cherenkov photons(i.e.,the imaging atmospheric Cherenkov technique).The telescope array has a low threshold energy and large field of view,and can continuously scan the area of the sky being observed,which is conducive to monitoring and promptly responding to transient phenomena.The process ofγ-hadron separation is essential in very-high-energy(>30 Ge V)γ-ray astronomy and is a key factor for the successful utilization of IACTs.In this study,Monte Carlo simulations were carried out to model the response of cosmic rays within the HADAR detectors.By analyzing the Hillas parameters and the distance between the event core and the telescope,the distinction between air showers initiated byγ-rays and those initiated by cosmic rays was determined.Additionally,a Quality Factor was introduced to assess the telescope’s ability to suppress the background and to provide a more effective characterization of its performance.

基坑开挖诱发侧方隧道变形的PCA-MLR预测方法

研究基坑开挖对侧方隧道变形的影响是岩土工程领域的热点与难点问题。为预测基坑开挖诱发临近侧方隧道变形,首先通过主成分分析方法(PCA)对侧方隧道变形指标影响因素进行降维处理并获取其主成分指标,然后采用多元线性回归方法(MLR)建立隧道变形指标与主成分指标间的关系模型,最后基于工程实例验证提出的PCA-MLR预测模型的正确性。研究结果表明:PCA-MLR模型考虑了基坑开挖诱发侧方隧道变形的高维度影响因素耦合作用,且实现了低维度主成分指标与变形指标间的关系模型建立。采用PCA-MLR模型预测的隧道最大水平及竖向位移与实测值的相对误差均小于10%,验证了提出模型的正确性与适用性。

夏垫断裂大胡庄探槽古地震事件分析

夏垫断裂是北京平原区内1条极为重要的隐伏活动断裂,同时也是1679年三河—平谷MS8.0地震的发震断层。为获取该断裂完整的古地震序列,主要开展了2方面工作:(1)以大胡庄探槽原始资料为基础,重新对探槽进行了解译,共识别出3个埋藏古土壤,6个崩积楔和1次砂土液化现象;(2)结合该断裂其它部位探槽揭示的古地震事件,通过对比各探槽标志性地层,建立不同探槽中古地震事件在同一时间轴上的联系,得到夏垫断裂完整的古地震序列。结果表明:距今31 ka以来,夏垫断裂共发生过11次古地震事件,古地震平均复发间隔约为2.8ka,但距今25~15 ka存在1个古地震丛集期,丛集期内共发生5次强震,平均复发间隔约为2.0 ka,反映出夏垫断裂活动性存在阶段性的差异。

三乙烯二胺交联季铵化聚芳醚砜电解质膜的制备与性能

采用聚芳醚砜为原料,经付克氯甲基化反应,以三乙烯二胺为交联剂,通过非均相和均相2种季铵化方式制备了2类燃料电池用交联型阴离子交换膜CQPAES。所制备CQPAES膜的离子交换容量为1. 15～1. 25 mmol/g。与非交联膜相比,交联膜的耐溶剂性、尺寸稳定性均得到了提高,在高温高压水中的水解稳定性、强碱条件下的化学稳定性显著增强。季铵化方式对交联膜性能影响的研究表明,均相季铵化膜与非均相季铵化膜相比,可更好地控制交联膜的溶胀,相应交联膜的离子电导率更高。交联剂加入量为0. 1～0. 2时,交联膜的综合性能最佳。

大气臭氧长期暴露对社区自然人群抑郁、焦虑和压力状况的影响

目的探讨大气污染物臭氧(O3)的长期暴露对社区人群抑郁、焦虑、压力状况的影响,为开展大气污染环境下人群心理健康干预工作提供科学依据。方法基于京津冀社区自然人群慢性病队列基线调查数据。使用问卷和抑郁-焦虑-压力量表(depression anxiety stress scale 21,DASS-21)收集研究对象基本信息,以及抑郁、焦虑和压力状况。通过监测站收集污染物数据并进行暴露评估,采用多水平Logistic回归方法分析O3长期暴露与社区人群抑郁、焦虑和压力发生风险的关系。结果纳入13446例研究对象(48.50±14.87岁),抑郁、焦虑和压力症状的检出率分别为10.5%、16.6%和5.2%,O3的三年平均浓度为100.20μg/m3。多水平模型分析结果发现O3每增加10μg/m3,抑郁[OR=1.154,95%CI(1.086,1.227)]、焦虑[OR=1.093,95%CI(1.042,1.147)]和压力[OR=1.142,95%CI(1.056,1.235)]的发生风险均有增加。敏感性分析模型结果相对稳定,显示O3对抑郁、焦虑和压力发生风险具有独立影响作用。结论大气污染物O3可能是导致人群负性心理症状的危险因素之一,应重点关注O3高暴露地区人群的心理健康。

Early intrajejunal nutrition: bacterial translocation and gut barrier function of severe acute pancreatitis in dogs

Objective: To evaluate the effect of early intrajejunalnutrition in attenuating bacterial and/or endotoxintranslocation and improving gut barrier function ofsevere acute pancreatitis (SAP) in dogs.Methods: 15 dogs were divided into parenteral nutrition(PN) group(7 dogs)and early intrajejunal nutrition(EIN) group(8). EIN was delivered nutrients via a nee-dle jejunostomy catheter feeding at 48h after operation.SAP model was induced by injecting 1 ml/kg of com-bined solution of 5% sodium taurocholate and 8000-10000 BAEE units trypsin/ml into the pancreas via thepancreatic duct. Systemic blood samples were ob-tained before and 1, 3, 5, 7 d following SAP, and culturedby aerobic as well as anaerobic bacterial growth. Systemicplasma and portal vein endotoxin levels were quantifiedby the chromogenic limulus amebocyte lysate (LAL)technique. Portal vein blood and specimens of tissuefrom the mesenteriolum and mesocolon lymph nodes,lung, pulmonary portal lymph nodes, pancreatitis tissueand periopancreas tissue were adopted before the experi-ment was finished. Aliquots of the homogenata were cul-tured as blood mentioned above to determine the magnitudeof the bacteria DNA, protein and the villi, the thickness ofmucosa, and the whole bowel wall of the ileum and trans-verse colon were measured.Results: The study showed that the levels of systemicplasma endotoxin and the magnitude of bacterialtranslocation to the portal and systemic blood and dis-tant organ were reduced significantly in the EINgroup as compared with the TPN group. The contentsof protein and DNA, the height of villi, the thicknessof mucosa and whole bowel wall of the ileum andtransverse colon in the EIN group were higher thanthose in the PN group.Conclusion: Our results suggested that EIN is safe andeffective to be adopted by intrajejunal delivery of nu-trients in SAP, decreases the occurrence of gut bacterialtranslocation, and improves the gut barrier function.

In situ forming hydrogels based on chitosan for drug delivery and tissue regeneration

In situ forming hydrogels with simple sol–gel transition are more practicable as injectable hydrogels for drug delivery and tissue regeneration. State-of-the-art in situ gelling systems can easily and efficiently be formed by different mechanisms in situ. Chitosan is a kind of natural polysaccharide that is widely exploited for biomedical applications due to its good biocompatibility, low immunogenicity and specific biological activities. Chitosan-based in situ gelling systems have already gained much attention as smart biomaterials in the development of several biomedical applications, such as for drug delivery systems and regeneration medicine. Herein, we review the typical in situ gelling systems based on chitosan and mechanisms involved in hydrogel forming, and report advances of chitosan-based in situ gels for the applications in drug delivery and tissue regeneration. Finally, development prospects of in situ forming hydrogels based on chitosan are also discussed in brief.

Long-term anodal block stimulation at sacral anterior roots promoted recovery of neurogenic bladder function in a rabbit model of complete spinal cord injury

A complete spinal cord injury model was established in experimental rabbits using the spinal cord clip compression method. Urodynamic examination was performed 2 weeks later to determine neurogenic bladder status. The rabbits were treated with anodal block stimulation at sacral anterior roots for 4 weeks. Electrical stimulation of sacral anterior roots improved urodynamic parameters of neurogenic bladder in rabbit models of complete spinal cord injury, effectively promoted urinary function, and relieved urinary retention. Immunohistochemistry results showed that a balance was achieved among expression of muscarinic receptor subunits M2, M3, ATP-gated ion channel P2X3 receptors, and 132-adrenergic receptor, and nerve growth factor expression decreased. These results suggested that long-term sacral anterior root stimulation of anodal block could＇be used to treat neurogenic bladder in a rabbit model of complete spinal cord injury.

Nrf2 epigenetic derepression induced by running exercise protects against osteoporosis

Osteoporosis(OP)is a common skeletal disease involving low bone mineral density(BMD)that often leads to fragility fracture,and its development is affected by multiple cellular pathologies and associated with marked epigenetic alterations of osteogenic genes.Proper physical exercise is beneficial for bone health and OP and reportedly possesses epigenetic modulating capacities;however,whether the protective effects of exercise on OP involve epigenetic mechanisms is unclear.Here,we report that epigenetic derepression of nuclear factor erythroid derived 2-related factor-2(Nrf2),a master regulator of oxidative stress critically involved in the pathogenesis of OP,mediates the significant osteoprotective effects of running exercise(RE)in a mouse model of OP induced by ovariectomy.We showed that Nrf2 gene knockout(Nfe2l2^(−/−))ovariectomized mice displayed a worse BMD reduction than the controls,identifying Nrf2 as a critical antiosteoporotic factor.Further,femoral Nrf2 was markedly repressed with concomitant DNA methyltransferase(Dnmt)1/Dnmt3a/Dnmt3b elevations and Nrf2 promoter hypermethylation in both patients with OP and ovariectomized mice.However,daily 1-h treadmill RE significantly corrected epigenetic alterations,recovered Nrf2 loss and improved the femur bone mass and trabecular microstructure.Consistently,RE also normalized the adverse expression of major osteogenic factors,including osteoblast/osteoclast markers,Nrf2 downstream antioxidant enzymes and proinflammatory cytokines.More importantly,the RE-conferred osteoprotective effects observed in the wild-type control mice were largely abolished in the Nfe2l2^(−/−)mice.Thus,Nrf2 repression due to aberrant Dnmt elevation and subsequent Nrf2 promoter hypermethylation is likely an important epigenetic feature of the pathogenesis of OP,and Nrf2 derepression is essential for the antiosteoporotic effects of RE.

Characteristics of the Outer Rainband Stratiform Sector in Numerically Simulated Tropical Cyclones:Lower-Layer Shear versus Upper-Layer Shear

Idealized numerical simulations are conducted in this study to comparatively investigate the characteristics of the stratiform sector in the outer rainbands of tropical cyclones(TCs)in lower-and upper-layer vertical wind shear(VWS)with moderate magnitude.Consistent with the results in previous studies,the outer rainband stratiform sector of the TCs simulated in both experiments is generally located downshear left.Upper-layer VWS tends to produce stronger asymmetric outflow at upper levels in the downshear-left quadrant than lower-layer shear.This stronger asymmetric outflow transports more water vapor radially outward from the inner core to the outer core at upper levels in the downshear-left quadrant in the upper-layer shear experiment.More depositional growth of both graupel and cloud ice thus occurs downshear left in upper layers in the outer core,yielding more diabatic heating and stronger upward motions,particularly in the stratiformdominated part of the stratiform sector in the upper-layer shear experiment.Resultingly,a better-organized stratiform sector in the outer rainbands is found in the upper-layer VWS experiment than in the lower-layer VWS experiment.The diabatic heating associated with the stratiform sector produces strong midlevel outflow on the radially inward side of,and weak midlevel inflow on the radially outward side of,the heating core,with lower-level inflow beneath the midlevel outflow and upper-level inflow above.The upper-layer VWS tends to produce a deeper asymmetric inflow layer in the outer rainband stratiform sector,with more significant lower-level inflow and tangential jets in the upper-layer VWS experiment.

Down-Regulation of Neurocan Expression in Reactive Astrocytes Promotes Axonal Regeneration and Facilitates the Neurorestorative Effects of Bone Marrow Stromal Cells in the Ischemic Rat Brain

脑卒中后缺血组织边界形成胶质疤痕,抑制轴突再生。神经蛋白聚糖是一种轴突延长抑制分子,在卒中后胶质疤痕中表达上调。骨髓基质干细胞(BMSCs)可降低胶质疤痕壁的厚度,加速缺血周边区的轴突重塑。为了进一步明确BMSCs在轴突再生中的作用及机制,本文重点研究脑缺血组织中BMSCs对神经蛋白聚糖表达的作用。31只成年雄性Wistar大鼠大脑中动脉阻塞(MCAo)2 h,24 h后从中选择16只给予尾静脉注射3×106鼠BMSCs(BMSCs组),15只注射磷酸盐缓冲生理盐水(对照组)。缺血后8 d处死实验大鼠,免疫染色表明反应性星形胶质细胞是神经蛋白聚糖的原始来源,且BMSCs组缺血半暗带脑组织的神经聚糖表达明显低于对照组,生长相关蛋白43表达高于对照组,这在蛋白印迹分析中得到确认。为了进一步检测BMSCs在星形胶质细胞神经蛋白聚糖表达中的作用,用激光捕获显微切割法从缺血周边区收集单纯的反应性星形胶质细胞。BMSCs组的神经蛋白聚糖基因表达明显下调(n=4/组)。原代培养的星形胶质细胞也表现出相同改变,糖氧剥离的星形胶质细胞再给氧时与BMSCs共培养会抑制神经蛋白聚糖基因的表达上调(n=3/组)。本研究表明BMSCs通过下调梗死周边星形胶质细胞中神经蛋白聚糖的表达来促进轴突再生。

Electrical stimulation of the sacral nerve anterior root following induced bladder detrusor contraction

The sacral nerve anterior root consists of parasympathetic nerves（dominating urinary bladder detrusor）and somatic motor nerves（dominating urethral sphincter）,and electrical stimulation to the sacral nerve anterior root induces simultaneous contraction of the bladder detrusor and urethral sphincter.Accordingly,urethral pressure exceeds intravesical pressure,resulting in little or no urination,kidney damage,and trembling of lower limbs due to high intravesical pressure.In the present study,sacral nerve posterior roots were transected in a spastic bladder rabbit model,followed by three-pole electrode and long-pulse electrical stimulation to the sacral anterior root.Intravesical and urethral pressures were simultaneously measured to verify the feasibility of anode inhibition to the sacral anterior root following induced detrusor contraction.As stimulus intensity increased,somatic motor nerves were increasingly inhibited; with a stimulus pulse width of 300 μs and stimulus current of 1.05 mA,urethral pressure was zero and average intravesical pressure was 3.84 kPa.In addition,detrusor contraction was displayed,and lower extremity trembling was significantly reduced.Three-pole electrode and long-pulse electrical stimulation to the sacral nerve anterior root induced detrusor contraction and inhibited low extremity trembling under electrical stimulation.

Differential protein expression in spinal cord tissue of a rabbit model of spinal cordischemia/reperfusion injury

New Zealand rabbits were randomly divided into an ischemia group （occlusion of the abdominal aorta for 60 minutes）, an ischemia-reperfusion group （occlusion of the abdominal aorta for 60 minutes followed by 48 hours of reperfusion） and a sham-surgery group. Two-dimensional gel electrophoresis detected 49 differentially expressed proteins in spinal cord tissue from the ischemia and ischemia/ reperfusion groups and 23 of them were identified by mass spectrometry. In the ischemia group, the expression of eight proteins was up regulated, and that of the remaining four proteins was down regulated. In the ischemia/reperfusion group, the expression of four proteins was up regulated, and that of two proteins was down regulated. In the sham-surgery group, only one protein was detected. In the ischemia and ischemia/reperfusion groups, four proteins overlapped between groups with the same differential expression, including three that were up regulated and one down regulated. These proteins were related to energy metabolism, cell defense, inflammatory mechanism and cell signaling.

Updated annotation of the wild strawberry Fragaria vesca V4 genome

The diploid strawberry Fragaria vesca serves as an ideal model plant for cultivated strawberry(Fragaria×ananassa,8x)and the Rosaceae family.The F.vesca genome was initially published in 2011 using older technologies.Recently,a new and greatly improved F.vesca genome,designated V4,was published.However,the number of annotated genes is remarkably reduced in V4(28,588 genes)compared to the prior annotations(32,831 to 33,673 genes).Additionally,the annotation of V4(v4.0.a1)implements a new nomenclature for gene IDs(FvH4_XgXXXXX),rather than the previous nomenclature(geneXXXXX).Hence,further improvement of the V4 genome annotation and assigning gene expression levels under the new gene IDs with existing transcriptome data are necessary to facilitate the utility of this high-quality F.vesca genome V4.Here,we built a new and improved annotation,v4.0.a2,for F.vesca genome V4.The new annotation has a total of 34,007 gene models with 98.1%complete Benchmarking Universal Single-Copy Orthologs(BUSCOs).In this v4.0.a2 annotation,gene models of 8,342 existing genes are modified,9,029 new genes are added,and 10,176 genes possess alternatively spliced isoforms with an average of 1.90 transcripts per locus.Transcription factors/regulators and protein kinases are globally identified.Interestingly,the transcription factor family FAr-red-impaired Response 1(FAR1)contains 82 genes in v4.0.a2 but only two members in v4.0.a1.Additionally,the expression levels of all genes in the new annotation across a total of 46 different tissues and stages are provided.Finally,miRNAs and their targets are reanalyzed and presented.Altogether,this work provides an updated genome annotation of the F.vesca V4 genome as well as a comprehensive gene expression atlas with the new gene ID nomenclature,which will greatly facilitate gene functional studies in strawberry and other evolutionarily related plant species.

Human endogenous retroviral syncytin exerts inhibitory effect on invasive phenotype of B16F10 melanoma cells

Objective; Fusogenic endogenous retroviral syncytin plays an important role in the formation of syncytiotrophoblasts in human placenta.Apart from its expression in placenta,brain and testis,syncytin has also been found in many cancers.Although syncytin has been proposed to serve as a positive prognostic marker in some cancers,the underlying mechanism is unclear.The aim of this study is to evaluate the effects of syncytin expression on the invasive phenotype of melanoma cells.Methods：The eukaryotic expression plasmid for syncytin-EGFP was constructed and transfected into B16F10 melanoma cells.The effect of syncytin on the invasion potential of rumor cells was evaluated in B16F10 subline cells that stably expressed syncytin-EGFP fusion protein or EGFP alone.Results：The B16F10 sublines that stably expressed syncytin-EGFP or EGFP alone were established respectively and confirmed by immunofluorescent and immtmoblotting assay.Syncytin expression in B16F10 cells was associated with decreased cell proliferation,migration and invasion.Multinucleated giant cells that contained as many as five nuclei were induced in syncytin-expressing cells.In addition,syncytin expression did not alter the sensitivity of B16F10 cells to trichosanthin,a toxin that damages syncytiotrophoblasts more efficiently than other tissues.Conclusions：These results suggest that syncytin expression in some cancers may confine their invasion potential and thus serve as a positive prognostic factor.

Author Correction:Updated annotation of the wild strawberry Fragaria vesca V4 genome

Since the publication of this article,the authors have noticed that the GeneIDs from new and original genome annotations don’t match in Table S6,the correct Table S6 is given here.The authors would like to apologize for this error.