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The capillary wave and initial spreading velocity in the spreading phase of drop impacting on a glass surface are studied experimentally, while the drop photos are obtained by using a high-speed video camera, which can catch up to 9000 images per second with an exposure time of 4 µs. A wide range of impact velocities are studied by varying the fall height, showing different capillary waves. All attention is given to the capillary wave and initial spreading velocity of drop. A non-linear relation between the wavelength and the impact velocity is found experimentally. Combined with the minimum spreading radius theory, a linear relation between the initial spreading velocity and the impact velocity is acquired.

In this paper, the Geometric Optics (GO)/Physical Optics (PO) method is improved to analyze the terahertz (THz)-wave scattering characteristics of objects with multiple small-scale grooves, where the grooves are of the same size. For the traditional GO/PO method, when the number of grooves reaches dozens or even hundreds, the existence of a large number of redundant intersection tests will be a main limitation to calculate the electromagnetic (EM) scattering in THz band. Therefore, in order to solve this problem, the scattered field from one of the grooves is computed using the GO/PO method and extended to obtain the scattered field of the other grooves according to their dimensional information. In this way, the computation load is effectively reduced. To demonstrate the validity of our method, the results are compared with those of MLFMM, traditional GO/PO method and experimental data. A good agreement is achieved. Meanwhile, the runtime of our method is compared with that of traditional GO/PO method, where the computational time is greatly saved. Furthermore, the scattering characteristics of objects with multiple small-scale grooves in THz band is studied. The simulation results show that the small-scale grooves will have a great effect on EM scattering characteristics in THz band.

We investigate free-running dual-comb pulses with overlapping spectra and well-controlled repetition rate difference in a single birefringent fiber cavity. Multiple linear and nonlinear soliton formation mechanisms in an all-fiber laser with partial polarization maintaining fiber are experimentally observed and validated for switchable and tunable dual-comb pulse emissions. Linear polarization mode dispersion is first exploited to emit polarization-multiplexed pulses with the upper limit of repetition rate difference at kHz level. By further tailoring linear birefringence, birefringence filter effect and nonlinear polarization evolution are well leveraged to emit hybrid mode-locked pulses with the lower limit at 10-Hz level. The lower limit of ∼12 Hz and nearly two order-of-magnitude tunable range of repetition rate difference are highlighted. Moreover, overlapping spectra and the passive mutual coherence between pulses in the free-running state are clarified, indicating the potential of the simplification of amplification system and single-cavity dual-comb source.

HIV-1 must overcome host antiviral restriction factors for efficient replication. We hypothesized that elevated levels of bone marrow stromal cell antigen 2 (BST-2), a potent host restriction factor that interferes with HIV-1 particle release in some human cells and is antagonized by the viral protein Vpu, may associate with viral control. Using cryopreserved samples, from HIV-1 seronegative and seropositive Black women, we measured in vitro expression levels of BST-2 mRNA using a real-time PCR assay and protein levels were validated by Western blotting. The expression level of BST-2 showed an association with viral control within two independent cohorts of Black HIV infected females (r=-0.53, p=0.015, [n =21]; and r=-0.62, p=0.0006, [n=28]). DNA methylation was identified as a mechanism regulating BST-2 levels, where increased BST-2 methylation results in lower expression levels and associates with worse HIV disease outcome. We further demonstrate the ability to regulate BST-2 levels using a DNA hypomethylation drug. Our results suggest BST-2 as a factor for potential therapeutic intervention against HIV and other diseases known to involve BST-2.

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To investigate the effects of serum high mobility group box 1 protein (HMGB1) on immune function and autophagy level of myocardial cells in rats with sepsis.Cecal ligation and perforation (CLP) was used to establish rat sepsis models. A total of 60 SD rats were selected and randomly divided into blank control group (BCG, n=20), sham group (SG, n=20) and cecal ligation and perforation group (CLPG, n=20). Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum HMGB1 level in sepsis rats. The expression levels of inflammatory factors in rats were detected, and the ratio of CD4+/CD8+ T cells was detected by flow cytometry. Western blot was used to detect the expression of autophagy-related protein microtubule-related protein 1 light chain 3 (LC3), Beclin-1 and apoptosis-related protein B lymphoblastoma-2 (Bcl-2), and cTnT protein, respectively.The level of serum HMGB1 in the CLPG was significantly higher than that in the BCG and the SG (p0.05). Compared with BCG and the SG, the CLPG had lower peripheral blood T lymphocyte proliferation response, lower IL-6 and IL-10 levels, and lower CD4+/CD8+T lymphocyte ratio (p0.05). Bcl-2 and cTnT in the CLPG and SG were higher than those in the BCG. LC3-11 and Beclin-1 expression in the CLPG were higher than those in the BCG and SG (p0.05). After HMGB1 interference in the CLPG, CD4+/CD8+T and Bcl-2 were significantly increased, while the other indicators were significantly decreased (p0.05). The level of serum HMGB1 is directly related to the severity of sepsis.The increase of serum HMGB1 level in sepsis has a significant impact on cellular immune dysfunction. Sepsis can effectively activate myocardial autophagy, and the level of autophagy shows an increasing trend.

HIV-1 must overcome host antiviral restriction factors for efficient replication. We hypothesized that elevated levels of bone marrow stromal cell antigen 2 (BST-2), a potent host restriction factor that interferes with HIV-1 particle release in some human cells and is antagonized by the viral protein Vpu, may associate with viral control. Using cryopreserved samples, from HIV-1 seronegative and seropositive Black women, we measured in vitro expression levels of BST-2 mRNA using a real-time PCR assay and protein levels were validated by Western blotting. The expression level of BST-2 showed an association with viral control within two independent cohorts of Black HIV infected females (r=-0.53, p=0.015, [n =21]; and r=-0.62, p=0.0006, [n=28]). DNA methylation was identified as a mechanism regulating BST-2 levels, where increased BST-2 methylation results in lower expression levels and associates with worse HIV disease outcome. We further demonstrate the ability to regulate BST-2 levels using a DNA hypomethylation drug. Our results suggest BST-2 as a factor for potential therapeutic intervention against HIV and other diseases known to involve BST-2.

Regression machine learning is widely applied to predict various materials. However, insufficient materials data usually leads to poor performance. Here, we develop a new voting data-driven method that could generally improve the performance of the regression learning model for accurately predicting properties of materials. We apply it to investigate a large family (2135) of two-dimensional hexagonal binary compounds focusing on ferroelectric properties and find that the performance of the model for electric polarization is indeed greatly improved, where 38 stable ferroelectrics with out-of-plane polarization including 31 metals and 7 semiconductors are screened out. By unsupervised learning, actionable information such as how the number and orbital radius of valence electrons, ionic polarizability, and electronegativity of constituent atoms affect polarization was extracted. Our voting data-driven method not only reduces the size of materials data for constructing a reliable learning model but also enables one to make precise predictions for targeted functional materials.

The Ground Wide Angle Camera Network (GWAC-N) is a network of robotic multi-aperture, multiple field-of-view (FoV) optical telescopes. The main contingent of GWAC-N instruments are provided by the Ground Wide Angle Cameras Array (GWAC-A), and additional, narrower FoV telescopes are utilized to provide fast multi-band follow-up capabilities. The primary scientific goal of the GWAC-N is to search for optical counterparts of gamma-ray bursts that will be detected by the Space Variable Object Monitor (SVOM) satellite. The GWAC-N performs many additional observing tasks including follow-up of Target of Opportunities (ToO) targets and the detection (and monitoring) of variable objects and optical transients. To handle these use cases (and to allow for extensibility), we have designed ten observation modes and 175 observation strategies, including a joint strategy with multiple GWAC-N telescopes for the follow-up of gravitational wave (GW) events. To perform these observations, we develop an Automatic Observation Management (AOM) system capable of performing object management, dynamic scheduling, automatic broadcasting across the network, and image handling. The AOM system combines the individual telescopes which comprise the GWAC-N into a network and smoothly organizes all associated operations, completely meeting the requirements dictated by GWAC-N. With its modular design, the AOM is scientifically and technically viable for other general-purpose telescope networks. As the GWAC-N extends and evolves, the AOM will greatly enhance its discovery potential. In this first paper of a series, we present the scientific goals of the GWAC-N and detail the hardware, software, and workflow developed to achieve these goals. The structure, technical design, implementation, and performance of the AOM system are also described in detail. We conclude with a summary of the current status of the GWAC-N and our near-future development plan.

The purpose of this study is to explore the effect of rehabilitation training on limb recovery of patients with cerebral infarction hemiplegia and the improvement of daily life activities of patients. In this study, 46 patients with cerebral infarction hemiplegia are selected as the research subjects. All of them receive rehabilitation training within 0 to 24 h after the acute phase of cerebral infarction and the patient’s vital signs are stable. After rehabilitation training for 2 w and 4 w, the motor function and daily life activity of hemiplegic limbs are evaluated, and the muscle strength recovery of patients is evaluated after rehabilitation training for 2 mo. The results show that after rehabilitation training, the muscle strength of hemiplegic patients with cerebral infarction is obviously restored, and the motor function of hemiplegic limbs and the ability of daily activities are significantly improved. Therefore, it can be concluded that rehabilitation training is conducive to promoting the recovery of limb motor function in patients with cerebral infarction hemiplegia and improving the life ability of patients, which has the promotion value. In the future research, large sample, multi-center randomized clinical control trial should be carried out to provide more reliable and effective rehabilitation mode for limb recovery of patients with cerebral infarction hemiplegia.

Human mobility impacts many aspects of a city, from its spatial structure1,2,3 to its response to an epidemic4,5,6,7. It is also ultimately key to social interactions8, innovation9,10 and productivity11. However, our quantitative understanding of the aggregate movements of individuals remains incomplete. Existing models--such as the gravity law12,13 or the radiation model14--concentrate on the purely spatial dependence of mobility flows and do not capture the varying frequencies of recurrent visits to the same locations. Here we reveal a simple and robust scaling law that captures the temporal and spatial spectrum of population movement on the basis of large-scale mobility data from diverse cities around the globe. According to this law, the number of visitors to any location decreases as the inverse square of the product of their visiting frequency and travel distance. We further show that the spatio-temporal flows to different locations give rise to prominent spatial clusters with an area distribution that follows Zipf's law15. Finally, we build an individual mobility model based on exploration and preferential return to provide a mechanistic explanation for the discovered scaling law and the emerging spatial structure. Our findings corroborate long-standing conjectures in human geography (such as central place theory16and Weber's theory of emergent optimality10) and allow for predictions of recurrent flows, providing a basis for applications in urban planning, traffic engineering and the mitigation of epidemic diseases.

This article introduces a 10kV/10kA module for DC Circuit Breaker(DCCB) based on 4-inch IGCT(Integrated gate commutated thyristor). The turn-off capability of 4-inch IGCT under reliable snubber conditions is researched at first. Then, the current-balancing experiment of the module is introduced. It is found that two IGCTs in parallel have a special current distribution problem at the moment of turn-off. The main influencing factors of current-balancing is analyzed during the module experiment. That is, the pressure distribution problem of IGCT is the major factor against current-balancing. Combining simulation and pressure experiments, the current-balancing problem of IGCT in parallel is solved by optimizing the module structure. The current-balancing coefficient of module is improved to above 0.93. Finally, the module passed the turn-off test verification of 10kA successfully, promoting the development of IGCT in the field of DCCB.

With the continuous development of informatization, big data has been increasingly used in the prevention and control of chronic diseases, which has a significant and considerable influence on public health. This paper briefly introduces the definition, characteristics and classification of big data and healthy big data, focusing on the analysis methods and their applications in tertiary prevention, as well as the challenges in technology, data management, sharing and quality, ethics and privacy, with the aim of providing more research approaches for healthy big data application in chronic disease prevention and control.随着信息化的不断发展，大数据（big data）正在越来越多地被运用于慢性病预防控制领域，对居民健康产生重大且深远的影响。本文简要地介绍了大数据和健康大数据（healthy big data）的定义、特征和分类；重点阐述了健康大数据的分析方法及其在慢性病三级预防中的应用；健康大数据应用所面临的技术难题、数据管理和共享、数据质量、伦理和隐私等诸多方面的挑战。为健康大数据在慢性病预防控制方面提供更多研究思路。.

The aim of this study was to explore the influences of micro ribonucleic acid (miR)-150 on the proliferation and apoptosis of mantle-cell lymphoma (MCL) cells and to investigate the potential underlying mechanism.Differentially expressed miRNAs in MCL tissues were excavated via microarray analysis of miRNA expression profiles. Subsequently, the expression of miRNAs were verified by quantitative Reverse Transcription-Polymerase Chain Reaction (RT-qPCR). The influence of miRNA expression on the survival of patients was detected based on clinical data. Besides, the potential targets of miRNAs were determined using Luciferase reporter gene assay combined with qRT-PCR and Western blotting. Primary tumor cells were extracted, and the influences of miR-150 expression on cell proliferation were detected via Cell Counting Kit (CCK)-8 assay and 5-ethynyl-2'-deoxyuridine (EdU) staining assay. Finally, Western blotting and flow cytometry were performed to explore the impact of miR-150 on the apoptosis of primary tumor cells.Microarray analysis of miRNA expression profiles and RT-qPCR verified that the expression levels of hsa-miR-486, hsa-miR-4746, and hsa-miR-3158 rose considerably in MCL tissues, while those of hsa-miR-29b-3p, hsa-miR-150, and hsa-miR-142-5p remarkably declined. According to the results of survival analysis, the survival time was notably prolonged in patients with higher expression levels of miR-150 and miR-486, especially in those with higher expression level of miR-150. Luciferase reporter gene assay and RT-qPCR and Western blotting results demonstrated that miR-150 negatively regulated the expression level of MET. Subsequent CCK-8 assay and EdU staining results revealed that up-regulation of miR-150 significantly suppressed the proliferation of primary MCL cells. Finally, Western blotting and flow cytometry found that increased expression of MET remarkably facilitated the apoptosis of primary MCL cells.MiR-150 inhibits the proliferation and promotes the apoptosis of MCL cells by negatively regulating MET expression.

The paper describes the conceptual design of a small-scale experiment within the fusion neutron source project ALIANCE (Axisymmetric LInear Advanced Neutron sourCE). The experimental machine is an axially symmetric magnetic plasma trap with a high mirror ratio, which focuses on the physical and engineering problems of mirror-based gasdynamic neutron sources. The specific research topics covered include the magnetohydrodynamic (MHD) stability of plasmas with high mirror ratios, the operation of the electrodes used for plasma stabilization, and problems related to particle and energy transport. ALIANCE-T features superconducting mirror solenoids that enable it to reach mirror ratios of ∼100 and a helicon plasma source with a power of up to 25 kW installed directly in the confinement zone between the mirrors. The expected plasma parameters are estimated using a simple analytical model, which takes into account gasdynamic axial plasma losses, cross-field transport, and the interaction of the plasma with neutral gas. It is projected that the machine will simultaneously achieve a plasma density >1013 cm−3 and a temperature >10 eV in a continuous discharge lasting for 1–8 h. This paper gives a detailed description of the key machine subsystems and introduces the analytical model used for calculation of the plasma parameters.

Nonlinear structures such as shock waves and vortices widely exist in nature and the Universe. They have also been separately observed in laser–plasma interactions. We show for the first time that two perpendicularly propagated collisionless electrostatic shock waves (CESs) can be excited by a moving electron vortex (EV). The latter is driven by an ultrashort intense laser pulse propagating through a sandwich nonuniform underdense plasma slab and is found to move perpendicularly to the density gradient. Two CESs are observed on both sides of the passing route of the EVs. The left-side CES is induced by a high-density electron layer, which originates from the vortex front and is compressed and accelerated during the EV motion. The right-side CES is induced by supersonic ions accelerated by the EVs directly. Ion acceleration by such CESs along the directions perpendicular to the vortex propagation is also observed. This study reveals the transformation of nonlinear structures and provides new routes for laser energy dissipation in plasmas.

In two-dimensional (2D) magnetic systems, large magnetic anisotropy is needed to stabilize the magnetic order according to Mermin-Wagner theorem. Based on density functional theory (DFT) calculations, we propose that the magnetic anisotropic energy (MAE) of 2D ferromagnetic (FM) semiconductors can be strongly enhanced in van der Waals heterostructures by attaching a nonmagnetic semiconductor monolayer with large spin-orbit coupling. We studied Cr2Ge2Te6/PtSe2 bilayer heterostructures, where each layer has been realized in recent experiments. The DFT calculations show that the MAE of Cr2Ge2Te6/PtSe2 is enhanced by 70%, and the Curie temperature TC is increased far beyond room temperature. A model Hamiltonian is suggested to analyze the DFT results, showing that both the Dzyaloshinskii-Moriya interaction and the single-ion anisotropy contribute to the enhancement of the MAE. Based on the superexchange picture, we find that the decreased energy difference between 3d orbitals of Cr and 5p orbitals of Te contributes partially to the increase of TC. Our present work indicates a promising way to enhance the MAE and TC by constructing van der Waals semiconductor heterostructures, which will inspire further studies on the 2D magnetic semiconductor systems., Comment: 10 pages, 5 figures

The aim of this study was to investigate the effect of leptin (Lep) on the proliferation, invasion and apoptosis of prostate cancer cells through the extracellular regulated protein kinase 1/2 (ERK1/2) signaling pathway.Prostate cancer DU145 cells in the logarithmic growth phase were randomly divided into Lep (10, 20, 40, 80, 160 and 320 ng/mL) groups and blank control (Con) group. After culture, the cells were treated for 6 h, 12 h and 24 h, respectively. The effects of Lep on the proliferation and invasion of DU145 cells were detected via methyl thiazolyl tetrazolium (MTT) assay and transwell chamber assay, respectively. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was carried out to examine the messenger ribonucleic acid (mRNA) expressions of ERK1/2, b-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) in DU145 cells after Lep treatment for 24 h. Thereafter, immunofluorescence assay was performed to detect the localization of ERK1/2 protein in prostate cancer DU145 cells. In addition, the expressions of phosphorylated (p)-ERK, ERK1/2 and apoptosis-related proteins, Bcl-2, Bax and cleaved cysteinyl aspartate specific proteinase (c-Caspase 3) in prostate cancer DU145 cells after treatment with different concentrations of Lep for 24 h were examined by Western blotting.MTT assay results showed that the proliferation rate of DU145 cells increased significantly at 6 h, 12 h and 24 h after 5-320 ng/mL of Lep treatment (p0.05). Transwell assay manifested that the number of invasive cells was significantly raised after Lep treatment for 24 h (p0.05). Meanwhile, the invasion ability of cells increased gradually with the elevation of Lep concentration. Subsequent qRT-PCR results demonstrated that after treatment with different concentrations of Lep, the mRNA expressions of ERK1/2 and Bcl-2 rose markedly (p0.05). However, the mRNA expression of Bax was remarkably down-regulated (p0.05) with the increase of Lep concentration in a concentration-dependent manner. According to the detection using a laser scanning confocal microscope, ERK1/2 red fluorescence showed punctiform aggregation, which was gradually raised with the increase of Lep concentration for 24 h. Moreover, Western blotting results denoted that with the increase of Lep concentration, the protein expressions of p-ERK, ERK1/2 and Bcl-2 were notably elevated (p0.05), while those of Bax and c-Caspase 3 were distinctly reduced (p0.05).Lep activation induces the proliferation, promotes the invasion and inhibits the apoptosis of prostate cancer cells through the ERK1/2 signaling pathway.

The aim of this study was to observe the expression of Klotho in renal tissues of mice with diabetic ne¬phropathy (DN), and to further explore the effect of Klotho on DN in mice and its mechanism. The 10-week-old mice in this experiment were divided into three groups: heterozygous db/+ mouse group (db/+ group, n=20), homozygous db/db mouse group (db/db group, n=20) and homozygous db/db mice + Klotho group (db/db + Klotho group, n=20). Firstly, Western blotting and immunohistochemical staining were applied to detect the protein expression of Klotho in the renal tissues of diabetic and non-diabetic mice of different ages. Finally, the protein expressions of fibroblast growth factor 2 (FGF2) and E-cadherin in the renal tissues of mice in each group were examined by Western blotting. The protein expression level of Klotho in the renal tissues of mice aged 10 and 16 weeks in the db/db group was remarkably lower than that in yhedb/+ group. In addition, it was found that db/db + Klotho group exhibited a prominently lower degree of interstitial fi¬brosis and content of Collagen I and Collagen III in the renal tissues than db/db group. Furthermore, it was revealed that the overexpression of Klotho could significantly repress the protein expression level of FGF2 but elevate that of E-cadherin in the renal tissues of DN mice. Klotho protein may ameliorate the renal injury and fibrosis in diabetic mice by inhibiting FGF2, so it is expected to become a targeted drug for DN.

1例因"喘鸣3个月，加重伴气促1个月余"的3月龄患儿及1例因"反复咳嗽、喘息半年，加重20 d"的12月龄患儿住院治疗，经过肺部CT血管成像、心脏彩超及气管镜检查，诊断为无名动脉压迫综合征（IACS）。IACS是引起婴幼儿反复喘鸣或喘息的重要原因，其常被漏诊。.

Harmful drinking causes serious consequences to social security as well as physical and mental health of the general public. The Global Burden of Disease Study (2017) showed that the number of alcohol-related deaths in China in 2017 was 1.82 times higher than that in 1990, and the population attributable fraction increased by 44.13%. The burden of disease caused by drinking alcohol had been increasing. By comparing with the comprehensive intervention strategy of restricting harmful drinking put forward by the World Health Organization, we suggest that the current interventions that need to be improved in China should include several aspects below: (1) strengthening the control of alcohol production, marketing and circulation, (2) restricting the availability of alcohol products for minors through enterprise self-discipline, laws and regulations, parents and school health education, (3) bridging gaps in appropriate techniques and services for alcohol restriction/abstinence in the health care system, (4) providing services such as rapid screening of alcohol dependence and short abstinence interventions, (5) strengthening restrictions on alcohol advertising especially in new media (e.g., online and social media) marketing practices for alcohol products, (6) conducting scientific research and evaluation on alcohol tax-related issues, and (7) regularly reviewing alcohol prices related to inflation and income levels.有害饮酒给社会安全和身心健康带来严重危害。全球疾病负担研究（2017）显示2017年我国饮酒致死的人数是1990年的1.82倍，导致的死亡人群归因分值增幅达44.13%。饮酒导致的疾病负担日益严重。通过与世界卫生组织提出的限制有害饮酒综合干预策略比对分析发现，我们认为当前我国有待完善的干预领域包括加强酒类生产、销售和流通环节的管控，通过企业自律、法规宣贯、家长和学校健康教育限制未成年人的酒类产品的可获得性；在医疗卫生体系中填补限酒/戒酒适宜技术和服务的空白，提供酒精依赖快速筛查、简短戒酒干预等服务；加强酒类广告的限制措施，尽快出台新媒体（如网络、社交媒体）酒类产品营销活动规范；针对酒税问题开展科学研究和评估，定期审查与通货膨胀和收入水平相关的酒类价格。.

Increasing evidence points to a role for antibody-mediated effector functions in preventing and controlling HIV infection. However, less is known about how these antibody effector functions evolve following infection. Moreover, how the humoral immune response is naturally tuned to recruit the antiviral activity of the innate immune system, and the extent to which these functions aid in the control of infection, are poorly understood. Using plasma samples from 10 hyper-acute HIV-infected South African women, identified in Fiebig stage I (the FRESH cohort), systems serology was performed to evaluate the functional and biophysical properties of gp120-, gp41-, and p24- specific antibody responses during the first year of infection. Significant changes were observed in both the functional and biophysical characteristics of the humoral immune response following acute HIV infection. Antibody Fc-functionality increased over the course of infection, with increases in antibody-mediated phagocytosis, NK activation, and complement deposition occurring in an antigen-specific manner. Changes in both antibody subclass and antibody Fc-glycosylation drove the evolution of antibody effector activity, highlighting natural modifications in the humoral immune response that may enable the directed recruitment of the innate immune system to target and control HIV. Moreover, enhanced antibody functionality, particularly gp120-specific polyfunctionality, was tied to improvements in clinical course of infection, supporting a role for functional antibodies in viral control.

CD8+ T cells play an important role in viral and tumour control. However, in human lymph nodes (LNs), only a small subset of CD8+ T cells called follicular CD8+ T cells (fCD8s) expresses CXCR5, the chemokine receptor required for cell migration into B cell follicles, thought to promote immune evasion. Here we obtained LNs from HIV infected persons to investigate regulation of CXCR5 expression in lymphoid CD8+ T cells, and compared this to the more abundant CXCR5 expressing T follicular CD4+ helper cells (GCTfh). Our results show that DNA hypermethylation and closed chromatin at the transcriptional start site (TSS) prevent CXCR5 expression in non-fCD8s. We also found that greater nucleosomal density at the CXCR5 TSS could be responsible for reduced CXCR5 expression in fCD8s relative to GCTfh. Together, these data provide critical insights into both the underlying molecular mechanisms that repress CXCR5 expression in non-fCD8s and the plausible mechanism responsible for the low CXCR5 expression in fCD8s, with implications for HIV cure strategies.Author SummaryA paucity of CD8+ T cells that express CXCR5, the chemokine receptor critical for entering the B cell follicles of secondary lymphoid tissues have recently been described. Animal studies have revealed transcriptional networks that govern the expression of CXCR5 in CD8+ T cells. However, it is not known if similar or additional networks regulate the expression of CXCR5 in human CD8+ T cells. In this study, we demonstrated that DNA methylation coupled with chromatin compaction at the transcriptional start site (TSS) of CXCR5 gene prevent the expression CXCR5 in human CD8+ T cells. In addition, we observed greater nucleosomal occupancy at the TSS of CXCR5 gene which could impact expression levels of CXCR5 in human CXCR5+CD8+ T cells. This study revealed multitiered epigenetic mechanisms that repress CXCR5 expression in human CD8+ T cells, with implications for HIV cure strategy or eradication of B cell-derived tumours.

术后出血是扁桃体切除术最常见的严重并发症，因假性动脉瘤导致术后反复顽固性出血较为罕见。我们报告1例32岁男性患者因扁桃体手术导致假性动脉瘤的顽固性术后出血，并经血管造影明确诊断后选择性动脉栓塞成功治愈，随访1个月无出血。在有持续出血的临床证据，但仍不能确定出血的确切来源，以及术腔可见难以消退的膨隆淤血斑块时，应考虑假性动脉瘤的可能，及早进行血管造影等相关检查，选择性动脉介入栓塞是假性动脉瘤合适的治疗方法。.

Genomic studies have significantly improved our understanding of hepatocellular carcinoma (HCC) biology and have led to the discovery of multiple protein-coding genes driving hepatocarcinogenesis. In addition, these studies have identified thousands of new non-coding transcripts deregulated in HCC. We hypothesize that some of these transcripts may be involved in disease progression. Long non-coding RNAs are a large class of non-coding transcripts which participate in the regulation of virtually all cellular functions. However, a majority of lncRNAs remain dramatically understudied. Here, we applied a pooled shRNA-based screen to identify lncRNAs essential for HCC cell survival. We validated our screening results using RNAi, CRISPRi, and antisense oligonucleotides. We found a lncRNA, termed ASTILCS, that is critical for HCC cell growth and is overexpressed in tumors from HCC patients. We demonstrated that HCC cell death upon ASTILCS knockdown is associated with apoptosis induction and downregulation of a neighboring gene, Protein Tyrosine Kinase 2 (PTK2), a crucial protein for HCC cell survival. Taken together, our study describes a new, non-coding RNA regulator of HCC.

Acute liver injury (ALI) leads to inflammatory response and tissue damage. Inflammatory activation of infiltrative macrophages plays a critical role in liver histology destruction and dysfunction. Hydroxytyrosol (3,4-dihydroxyphenil-ethanol, HT), one of the polyphenols extracted from extra virgin olive oil, currently acts as a treatment for neuroinflammatory responses, but its effect on ALI is elusive. The present study aims to examine the mechanism of HT in macrophages inflammation and evaluate treatment effect of HT on ALI.In vitro, the expressions of type M1/M2 macrophages biomarkers (CD11c/CD206) and cytokines (TNF-α, IL-1β, IL-6, IL-10, IL-4) following lipopolysaccharide (LPS) stimulation and HT administration were detected using immunofluorescence, quantitative real-time polymerase chain reaction (qRT-PCR), and enzyme-linked immunosorbent assay (ELISA). Mechanically, HT was used to treat cells and phosphorylation level of extracellular-signal-regulated kinase 1/2 (ERK1/2) protein in cells was analyzed using Western blotting. In murine acute liver injury, inflammatory cytokines and liver injury degree were exhibited by qRT-PCR, IHC and HE staining. Furthermore, hepatic function was exhibited via hepatic metabolic enzymes (ALT/AST) and total bilirubin (TBil) in serum.It was demonstrated that HT treatment attenuated M1 macrophages and increased M2 macrophages after LPS stimulation. Furthermore, the pro-inflammatory cytokine level was descended, while an-inflammatory cytokine was increased via HT suppressing ERK pathway in macrophages. In vivo, HT reduced inflammatory level and mitigated hepatic histological injury, thus ameliorating liver function after acute liver injury.HT exerts a hepatoprotective and anti-inflammation effect on acute liver injury, which restrains inflammation by inhibiting ERK pathway and regulating macrophages polarization. Moreover, HT prevents liver tissues from inflammatory injury. Therefore, HT serves as a potential implication to treat ALI through modulating inflammation of macrophages.

To explore whether long non-coding RNA nuclear enriched abundant transcript 1 (lncRNA NEAT1) could regulate Hodgkin's lymphoma (HL) cell proliferation and invasion through miR-448, which could target doublecortin like kinase 1 (DCLK1) and mediate DCLK1 expression.Expressions of NEAT1, miR-448 and DCLK1 were evaluated by qRT-PCR or Western blot assay. Cell Counting Kit-8 (CCK-8) and transwell assay were utilized to detect cell proliferation and invasion capability in L428 cells respectively. The target relationship between NEAT1, miR-448 and DCLK1 was confirmed by Luciferase reporter assay.QRT-PCR results showed that NEAT1 expressed higher in HL tissues and cell lines than that in controls. In vitro experiments, NEAT1 downregulation could decrease cell proliferation and invasion capability in L428 cells. NEAT1 directly interacted with miR-448 and negatively regulated it. Moreover, DCLK1 was confirmed as a target of miR-448. DCLK1 expression was increased in L428 cells and positively regulated by NEAT1. NEAT1 overexpression upregulated the protein level of DCLK1 in L428 cells according to Western blot analysis. Additionally, DCLK1 overexpression could reverse the suppression on cell proliferation and invasion capability induced by NEAT1 knockdown or miR-448 overexpression.NEAT1 might be contributed to HL progression by promoting cell proliferation and invasion capability via miR-448 mediated DCLK1 expression.

Background: Early combination antiretroviral therapy (cART) reduces the size of the viral reservoir in paediatric and adult HIV infection. Very early-treated children may have higher cure/remission potential. Methods: In an observational study of 151 in utero (IU)-infected infants in KwaZulu-Natal, South Africa, whose treatment adhered strictly to national guidelines, 76 infants diagnosed via point-of-care (PoC) testing initiated cART at a median of 26 h (IQR 18–38) and 75 infants diagnosed via standard-of-care (SoC) laboratory-based testing initiated cART at 10 days (IQR 8–13). We analysed mortality, time to suppression of viraemia, and maintenance of aviraemia over the first 2 years of life. Findings: Baseline plasma viral loads were low (median 8000 copies per mL), with 12% of infants having undetectable viraemia pre-cART initiation. However, barely one-third (37%) of children achieved suppression of viraemia by 6 months that was maintained to >12 months. 24% had died or were lost to follow up by 6 months. Infant mortality was 9.3%. The high-frequency virological failure in IU-infected infants was associated not with transmitted or acquired drug-resistant mutations but with cART non-adherence (plasma cART undetectable/subtherapeutic, p Interpretation: The success of early infant testing and cART initiation strategies is severely limited by subsequent cART non-adherence in HIV-infected children. Although there are practical challenges to administering paediatric cART formulations, these are overcome by mothers who themselves are cART-adherent. These findings point to the ongoing obligation to address the unmet needs of the mothers. Eliminating the particular barriers preventing adequate treatment for these vulnerable women and infants need to be prioritised in order to achieve durable suppression of viraemia on cART, let alone HIV cure/remission, in HIV-infected children.