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巨噬细胞活化综合征是一种自身免疫病继发的噬血细胞性淋巴组织细胞增生症，临床表现为发热、肝脾大、全血细胞减少、肝功能不全、凝血异常、高甘油三酯血症、高铁蛋白等，骨髓有噬血细胞现象，其分子机制可能与CD8

Various theories beyond the standard model predict new interactions mediated by new light particles with very weak couplings to ordinary matter. Interactions between polarized electrons and unpolarized nucleons proportional to g_{V}^{N}g_{A}^{e}σ[over →]·v[over →] and g_{A}^{N}g_{A}^{e}σ[over →]·v[over →]×r[over →] are two such examples, where σ[over →] is the spin of the electrons, r[over →] and v[over →] are position and relative velocity between the polarized electrons and nucleons, g_{V}^{N}/g_{A}^{N} is the vector or axial-vector coupling constant of the nucleon, and g_{A}^{e} is the axial-vector coupling constant of the electron. Such interactions involving a vector or axial-vector coupling g_{V}^{N}/g_{A}^{N} at one vertex and an axial-vector coupling g_{A}^{e} at the polarized electron vertex can be induced by the exchange of spin-1 bosons. We report new experimental upper limits on such exotic spin-velocity-dependent interactions of the electron with nucleons from dedicated experiments based on a recently proposed scheme. We rotationally modulated two ∼6 Kg source masses at a frequency of 20 Hz. We used four identical atomic magnetometers in an array form to increase the statistics and cancel the common-mode noise. We applied a data processing method based on high precision numerical integration for the four harmonic frequencies of the signal. We reverse the rotation direction of the source masses to flip the signal due to the new interactions; thus, we can apply the [+1,-3,+3,-1] weighting method to remove possible slow drifting. Our constraint on the product of vector and axial-vector couplings is |g_{V}^{N}g_{A}^{e}|2.1×10^{-34} and on the product of axial-vector and axial-vector couplings is |g_{A}^{N}g_{A}^{e}|2.4×10^{-22} for an interaction range of 10 m. The new constraints on vector-axial-vector interaction improved by as much as more than 4 orders of magnitude and on axial-axial interaction by as much as 2 orders of magnitude in the corresponding interaction range, respectively.

The comparative studies of grain refinement of commercial purity Mg by CaO/Ca addition have been investigated by using TP-1 tests, optical microscope, XRD characterisation and TEM (STEM) observatio...

The method of participant-observation is fundamental to ethnomethodological, ethnographic video-based fieldwork. Collecting data of the embodied interactions of non-speaking Autistic individuals surfaces questions that are central to the nature of video-based fieldwork: What are the technical and interactional challenges of navigating the researcher’s multiple participant roles during data collection? What are ethical issues that arise with emergent participant roles during data collection? Grounded in two contrasting pieces of data—one of two siblings in a display of intimacy, and another of a student displaying distress—this paper examines the multiple participant roles the EMCA researcher navigates moment-by-moment during the data collection process. Studying these roles unearths participant orientations to the camera, the complex interactional work undertaken by the researcher, and ethical dilemmas when the positionality of the researcher becomes blurred.

Due to the durability and persistence of reservoirs of HIV-1-infected cells, combination antiretroviral therapy (ART) is insufficient in eradicating infection. Achieving HIV-1 cure or sustained remission without ART treatment will require the enhanced and persistent effective antiviral immune responses. Chimeric Antigen Receptor (CAR) T-cells have emerged as a powerful immunotherapy and show promise in treating HIV-1 infection. Persistence, trafficking, and maintenance of function remain to be a challenge in many of these approaches, which are based on peripheral T cell modification. To overcome many of these issues, we have previously demonstrated successful long-term engraftment and production of anti-HIV CAR T cells in modified hematopoietic stem cells (HSCs) in vivo. Here we report the development and in vivo testing of second generation CD4-based CARs (CD4CAR) against HIV-1 infection using a HSCs-based approach. We found that a modified, truncated CD4-based CAR (D1D2CAR) allows better CAR-T cell differentiation from gene modified HSCs, and maintains similar CTL activity as compared to the full length CD4-based CAR. In addition, D1D2CAR does not mediate HIV infection or stimulation mediated by IL-16, suggesting lower risk of off-target effects. Interestingly, stimulatory domains of 4-1BB but not CD28 allowed successful hematopoietic differentiation and improved anti-viral function of CAR T cells from CAR modified HSCs. Addition of 4-1BB to CD4 based CARs led to faster suppression of viremia during early untreated HIV-1 infection. D1D2CAR 4-1BB mice had faster viral suppression in combination with ART and better persistence of CAR T cells during ART. In summary, our data indicate that the D1D2CAR-41BB is a superior CAR, showing better HSC differentiation, viral suppression and persistence, and less deleterious functions compared to the original CD4CAR, and should continue to be pursued as a candidate for clinical study., Author summary Engineering T cells with anti-HIV chimeric antigen receptors (CAR) has emerged as a promising strategy to control HIV infection through a genetic vaccination strategy. Here we report a novel CAR-based approach targeting HIV infection using the genetic modification of blood forming hematopoietic stem cells (HSCs). This novel CAR approach uses a modified HIV receptor molecule (the primary HIV receptor CD4) as well as anti-HIV agents to modify HSCs to allow them to develop into cells that are protected from HIV infection and target HIV infected cells for the life of the individual. We found this latest generation of CARs successfully modified and allowed in vivo engraftment that resulted in the development of effective anti-HIV CAR T cells with robust memory formation and viral control. Our study highlights the identification of a next-generation CAR molecule that protected cells from infection, targeted and reduced HIV burdens, and serves as an ideal developmental candidate for further clinical studies.

In April 2016, the Global Polio Eradication Initiative (GPEI) adjusted its polio vaccination strategy, converting trivalent oral polio vaccine (tOPV) into bivalent oral polio vaccine (bOPV), and withdrawing type 2 oral polio vaccine (OPV2) globally. However, after the withdrawal of OPV2, there were many outbreaks of type-2 circulating vaccine-derived poliovirus (cVDPV2) in Asia and Africa. In order to eradicate poliovirus completely, GPEI launched the research and development of the novel serotype 2 oral polio vaccine (nOPV2) in 2010 and considering whether it is necessary to reuse OPV. This paper summarizes the epidemiological situation of cVDPV2 before and after OPV2's withdrawal, the related factors affecting the reuse of OPV and the related research progress of nOPV2.全球消灭脊髓灰质炎行动（GPEI）于2016年4月调整脊髓灰质炎疫苗免疫接种战略，将三价口服脊髓灰质炎疫苗（tOPV）转换为二价口服脊髓灰质炎疫苗（bOPV），并在全球全面撤出Ⅱ型口服脊髓灰质炎减毒活疫苗（OPVⅡ）。然而在OPVⅡ撤出以后，亚洲和非洲多地暴发Ⅱ型循环疫苗衍生脊髓灰质炎病毒（cVDPVⅡ）。为了彻底消灭脊髓灰质炎病毒，GPEI于2010年启动研发新型Ⅱ型口服脊髓灰质炎减毒活疫苗（nOPVⅡ），并于近年开始考虑是否有必要重启OPV。本文概述了OPVⅡ撤出前后cVDPVⅡ的流行病学情况，影响OPV重启的相关因素以及nOPVⅡ相关研究进展。.

Electroencephalogram (EEG) signals are inevitably interfered by artifacts during the acquisition process. These artifacts make analysis and interpretation of EEG data difficult. A major source of artifacts in EEG is the ocular activity. Therefore, it is important to remove the ocular artifacts before further processing the EEG data.In this study, we proposed an automatic ocular artifacts removal (AOAR) method for EEG signals based on non-negative matrix factorization (NMF) and empirical mode decomposition (EMD). First, the amplitude of EEG data was normalized in order to ensure the non-negativity of EEG data. Then, the normalized EEG data were decomposed into a set of components using NMF. The components containing ocular artifacts were extracted automatically through fractal dimension. Subsequently, the temporal activities of these components were adaptively decomposed into some intrinsic mode functions (IMFs) by EMD. The IMFs corresponding to ocular artifacts were removed. Finally, the denoised EEG data were reconstructed.The proposed method was tested against the other seven methods. In order to assess the effectiveness and reliability of the AOAR method in processing EEG data, experiments on ocular artifacts removal were performed using semi-simulated EEG data. Experimental results indicated that the proposed method was superior to other methods in terms of root mean squared error, signal noise rate and correlation coefficient, especially in the cases with lower signal noise rate. To further evaluate the application potentials of the proposed method in real life, the proposed method with the counterparts were applied to preprocess the real EEG data recorded from children with and without attention-deficit/hyperactivity disorder (ADHD). After artifacts rejection, the ERP feature was extracted for classification. The AOAR performed the best for distinguishing the ADHD children from others.These results indicate that the proposed AOAR method has great prospects in removing ocular artifacts from EEG.

We report demonstration of a new spectrally-controllable device, based on a sequence of linear polarizers and birefringent plates, which allows to accurately and adjustably tailor its spectral filtering properties for achieving complete gain-narrowing compensation over ~30nm of signal bandwidth in an Yb-doped fiber system with the total gain reaching 150dB. The experimental demonstration was performed in a regenerative Yb-fiber amplifier system with controllable number of passes, allowing to characterize both signal spectral-narrowing, and as well as spectral compensation at varying levels of achieved total gain. This result opens a pathway towards 100fs duration multi-mJ pulses from fiber CPSA systems.

Regular exercise induces intramuscular triglyceride accumulation with improved mitochondrial ability, but the mechanism remains unknown. The glycolytic product of exercise, lactate, has long been rec-ognized to suppress lipolysis and promote lipogenesis in adipocytes through inhibition of the cAMP-PKA pathway by activation of the G protein-coupled receptor (GPR81). However, whether lactate results in a similar process in skeletal muscle is unclear. Here, by using intramuscular injection of lactate to the gastrocnemius, the lipid metabolism effects were investigated in rat skeletal muscle. Firstly, the lactate-injection effect was verified by comparing changes in blood lactate levels from injection and exercise (30 min, 31 m/min, treadmill running). After five weeks of lactate intervention, intramuscular triglyceride levels in the gastrocnemius and the proportion of epididymis adipose mass to body weight increased. Chronic intramuscular injection of lactate elevated lactate receptor, GPR81, and reduced cAMP response element-binding (CREB) and P-CREB abundance in the gastrocnemius. Additionally, there was a significant decline in lipolytic-related proteins (AMPK, P-AMPK, P-HSL, CPT-1B, TGF-β2, SDHA) and a significant increase in fat synthesis proteins (SREBP-1C, PPAR-γ). Surprisingly, mitochondrial biomarkers (PGC-1α, CS) were also increased in the gastrocnemius, suggesting that chronic lactate might promote mitochondria biogenesis. Together, these results demonstrated that lactate may play a crucial role in triglyceride storage and mitochondria biogenesis in the skeletal muscle of rat.

Broadly neutralizing antibodies (bNAbs) directed to HIV-1 have shown promise at suppressing viremia in animal models. However, the use of bNAbs for the central nervous system (CNS) infection is confounded by poor penetration of the blood brain barrier (BBB). Typically, antibody concentrations in the CNS are extremely low; with levels in cerebrospinal fluid (CSF) only 0.1% of blood concentrations. Using a novel nanotechnology platform, which we term nanocapsules, we show effective transportation of the human bNAb PGT121 across the BBB in infant rhesus macaques upon systemic administration up to 1.6% of plasma concentration. We demonstrate that a single dose of PGT121 encased in nanocapsules when delivered at 48h post-infection delays early acute infection with SHIVSF162P3 in infants, with one of four animals demonstrating viral clearance. Importantly, the nanocapsule delivery of PGT121 improves suppression of SHIV infection in the CNS relative to controls., Author summary In patients where HIV-1 is fully suppressed by antiretroviral drugs, HIV-1 still persists in reservoirs. If antiretroviral drugs are stopped, the virus will emerge from these reservoirs and re-seeds systemically. The central nervous system (CNS) is proposed to be a tissue compartment that harbors other HIV-1 reservoirs. A key obstacle that constrains the treatment for the CNS infection is the blood–brain barrier (BBB), a highly restrictive barrier separating the circulating blood from the brain and extracellular fluid in the CNS, which impedes ~98% of the small molecule therapeutics and almost all macromolecules including broadly neutralizing antibodies (bNAbs) directed to HIV-1. Our “nanocapsule” strategy is based on a nanotechnology wherein bNAb molecules are encapsulated within nanocapsules of which the surface contains abundant choline and acetylcholine analogues. This design allows the nanocapsules to effectively cross the BBB to deliver bNAbs into the CNS upon systemic administration and show an impact of bNAb on CNS reservoirs in SHIV infected infant macaques.

BackgroundDespite the numerous applications of monoclonal antibodies (mAbs) in cancer therapeutics, animal models available to test the therapeutic efficacy of new mAbs are limited. NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice are one of the most highly immunodeficient strains and are universally used as a model for testing cancer-targeting mAbs. However, this strain lacks several factors necessary to fully support antibody-mediated effector functions—including antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and complement-dependent cytotoxicity (CDC)—due to the absence of immune cells as well as a mutation in the Hc gene, which is needed for a functional complement system.MethodsWe have developed a humanized mouse model using a novel NSG strain, NOD.Cg−Hc1Prkdcscid Il2rgtm1Wjl/SzJ (NSG−Hc1), which contains the corrected mutation in the Hc gene to support CDC in addition to other mechanisms endowed by humanization. With this model, we reevaluated the anticancer efficacies of nanoencapsulated rituximab after xenograft of the human Burkitt lymphoma cell line 2F7-BR44.ResultsAs expected, xenografted humanized NSG−Hc1 mice supported superior lymphoma clearance of native rituximab compared with the parental NSG strain. Nanoencapsulated rituximab with CXCL13 conjugation as a targeting ligand for lymphomas further enhanced antilymphoma activity in NSG−Hc1 mice and, more importantly, mediated antilymphoma cellular responses.ConclusionsThese results indicate that NSG−Hc1 mice can serve as a feasible model for both studying antitumor treatment using cancer targeting as well as understanding induction mechanisms of antitumor cellular immune response.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) with CCR5– donor cells is the only treatment known to cure HIV-1 in patients with underlying malignancy. This is likely due to a donor cell–mediated graft-versus-host effect targeting HIV reservoirs. Allo-HSCT would not be an acceptable therapy for most people living with HIV due to the transplant-related side effects. Chimeric antigen receptor (CAR) immunotherapies specifically traffic to malignant lymphoid tissues (lymphomas) and, in some settings, are able to replace allo-HSCT. Here, we quantified the engraftment of HSC-derived, virus-directed CAR T cells within HIV reservoirs in a macaque model of HIV infection, using potentially novel IHC assays. HSC-derived CAR cells trafficked to and displayed multilineage engraftment within tissue-associated viral reservoirs, persisting for nearly 2 years in lymphoid germinal centers, the brain, and the gastrointestinal tract. Our findings demonstrate that HSC-derived CAR+ cells reside long-term and proliferate in numerous tissues relevant for HIV infection and cancer.

Ferroptosis is a new programmed cell death characterized by iron dependent and intracellular oxidative accumulation. Current studies have confirmed that ferroptosis is involved in the occurrence and development of neurotoxicity injury, tumors, cardiovascular diseases and other diseases. This paper reviews the mechanisms of ferroptosis and its role in related diseases based on recent studies.铁死亡是以铁依赖性的、细胞内氧化堆积为主要特征的新型细胞死亡方式。目前研究表明铁死亡参与神经毒性损伤、肿瘤、心血管疾病等多种疾病的发生发展过程。我们围绕铁死亡的发生机制及其与相关疾病的关系进行综述。.

人口老龄化和老年人的多种慢性基础性疾病并发给医疗卫生系统带来了严峻挑战。感染性疾病对老年人危害严重，而接种疫苗是预防感染最经济有效的手段。本文主要通过回顾分析流感病毒、肺炎链球菌、水痘-带状疱疹病毒（VZV）感染对老年人造成的健康和经济负担，以及相应疫苗的作用、效果及接种必要性，提出一系列促进老年人接种疫苗的措施建议，一是提升老年人和医务人员对疾病和疫苗的认识，加强科普宣传；二是倡导医防协同，鼓励医务人员为"适龄人群"开具疫苗健康处方；三是提升新型疫苗的研发和生产供应能力；四是制定和开发政策，解决支付障碍，提升接种便利性。通过综合措施提高疫苗接种率，降低感染性疾病和相关并发症的发生风险，提升老年人健康水平和生活生命质量，减轻社会和家庭的经济负担，降低医疗资源负荷，助力健康中国行动。.

The etiological factors of portal hypertension are different. Therefore, there are many types of esophagogastric varices and the combined diseases are serious. However, with the continuous development of treatment technology, the importance of multidisciplinary team in the management of portal hypertension has gradually become well-known. Importantly, finding problems from the case discussion, summarizing the characteristics, conducting further clinical studies to evaluate the effect of endoscopic treatment on varicose veins, improving the safety of tissue adhesives therapy through the technological innovation, summarizing the treatment experience from treatment failure, and paying attention to the pathological examination of unexplained portal hypertension, and the comprehensive diagnosis and treatment under special circumstances through multidisciplinary team has provided us high-quality clinical research evidence for different phases and different treatment plan, and recognized the risk assessment and personalized precise diagnosis and treatment in patients with portal hypertension.门静脉高压的病因各异，食管胃静脉曲张类型多样，合并疾病危重，随着治疗技术的不断进展，门静脉高压多学科团队协作的重要性逐渐凸显。从病例讨论中发现问题，总结特点，进一步通过开展临床研究评价内镜治疗静脉曲张的效果，通过技术创新提高组织胶治疗的安全性，从失败中总结治疗经验，重视不明原因门静脉高压的病理学检查，对特殊状态门静脉高压的多学科综合诊疗。为门静脉高压患者不同阶段和不同状态的治疗选择提供高质量临床研究证据，实现对门静脉高压患者的风险分层和个体化精准诊疗。.

Background: Current understanding of hematopoiesis is largely derived from mouse models that are physiologically distant from humans. Humanized mice provide the most physiologically relevant small animal model to study human diseases, most notably preclinical gene-therapy studies. However, the clonal repopulation dynamics of human hematopoietic stem and progenitor cells (HSPC) in these animal models is only partially understood. Using a new clonal tracking methodology designed for small sample volumes, we aim to reveal the underlying clonal dynamics of human cell repopulation in a mouse environment. Methods: Humanized BLT (bone marrow-liver-thymus) mice were generated by transplanting lentiviral vector transduced human fetal liver HSPC (FL-HSPC) in NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice implanted with a piece of human fetal thymus. We developed a methodology to track vector integration sites (VIS) in a mere 25μl of mouse blood for longitudinal and quantitative clonal analysis of human HSPC repopulation in mouse environment. We explored transcriptional and epigenetic features of human HSPC for possible VIS bias. Results: 897 HSPC clones were longitudinally tracked in BLT mice — providing a first-ever demonstration of clonal dynamics and competitive expansion of therapeutic and control vector-modified human cell populations simultaneously repopulating in the same humanized mice. The polyclonal repopulation stabilized at 19 weeks post-transplant and the contribution of the largest clone doubled within 4 weeks. Moreover, 550 (~60%) clones persisted over 6 weeks and were highly shared between different organs. The normal clonal profiles confirmed the safety of our gene therapy vectors. Multi-omics analysis of human FL-HSPC revealed that 54% of vector integrations in repopulating clones occurred within ±1kb of H3K36me3-enriched regions. Conclusions: Human repopulation in mice is polyclonal and stabilizes more rapidly than that previously observed in humans. VIS preference for H3K36me3 has no apparent negative effects on HSPC repopulation. Our study provides a methodology to longitudinally track clonal repopulation in small animal models extensively used for stem cell and gene-therapy research and with lentiviral vectors designed for clinical applications. Results of this study provide a framework for understanding the clonal behavior of human HPSC repopulating in a mouse environment, critical for translating results from humanized mice models to the human settings.

A novel approach enables a direct comparison of anti-HIV– and non–gene-modified stem-cell engraftment in an HIV-1–infected host., Despite advances in hematopoietic stem/progenitor cell (HSPC) transplant for HIV-1–infected patients, the impact of a preexisting HIV-1 infection on the engraftment and clonal repopulation of HSPCs remains poorly understood. We have developed a long terminal repeat indexing-mediated integration site sequencing (LTRi-Seq) method that provides a multiplexed clonal quantitation of both anti–HIV-1 RNAi (RNA interference) gene-modified and control vector-modified cell populations, together with HIV-1–infected cells—all within the same animal. In our HIV-1–preinfected humanized mice, both therapeutic and control HSPCs repopulated efficiently without abnormalities. Although the HIV-1–mediated selection of anti–HIV-1 RNAi-modified clones was evident in HIV-1–infected mice, the organ-to-organ and intra-organ clonal distributions in infected mice were indistinguishable from those in uninfected mice. HIV-1–infected cells showed clonal patterns distinct from those of HSPCs. Our data demonstrate that, despite the substantial impact of HIV-1 infection on CD4+ T cells, HSPC repopulation remains polyclonal, thus supporting the use of HSPC transplant for anti-HIV treatment.

The methods of quickly achieving the adiabatic effect through a non-adiabatic process has recently drawn widely attention both in quantum and classical regime. In this work ,we study the classical adiabatic shortcut for two- and three-Level atoms by transforming the quantum version into classical one via quantum-classical corresponding theory. The results shows that, the additional couplings between the oscillators can be used to speed up the adiabatic evolution of coupled oscillators. Furthermore, we find that the quantum-classical correspondence theory still holds for the couter-adiabatic driving Hamiltonian for the TQD. This means that, we can obtain the counter-adiabatic driving Hamiltonian for a classical system by averaging over its quantum correspondence in a quantum system. This provides a feasible way to study the classical adiabatic shortcut and the simulation for the quantum adiabatic shortcut in a classical system.

Since December 2019, COVID-19, a new emerging infection disease, has spread in 27 countries and regions. The clusters of many cases were reported with the epidemic progresses. We collected currently available information for 377 COVID-19 clusters (1 719 cases), excluded the hospital clusters and Hubei cases, during the period from January 1 to February 20, 2020. There were 297 family clusters (79%), case median was 4; 39 clusters of dining (10%), case median was 5; 23 clusters of shopping malls or supermarkets (6%), case median was 13; 12 clusters of work units (3%), case median was 6, and 6 clusters of transportation. We selected 325 cases to estimate the incubation period and its range was 1 to 20 days, median was 7 days, and mode was 4 days. The analysis of the epidemic situation in a department store in China indicated that there was a possibility of patients as the source of infection during the incubation period of the epidemic. From February 5 to 21, 2020, 634 persons were infected on the Diamond Princess Liner. All persons are susceptible to the 2019 coronavirus. Age, patients during the incubation period and the worse environment might be the cause of the cases rising. The progress of the two typical outbreaks clearly demonstrated the spread of the early cases in Wuhan. In conclusion, screening and isolating close contacts remained essential other than clinical treatment during the epidemic. Especially for the healthy people in the epidemic area, isolation was the key.新型冠状病毒肺炎作为新发传染病，自2019年12月发现以来，全球27个国家和地区已有病例报告。随着疫情的发展，聚集性疫情所占的发病数比例不断增加，尤其是武汉市和湖北省以外地区，暴露来源发生很大变化。本研究收集2020年1月1日至2月20日期间非医疗机构新型冠状病毒肺炎聚集性疫情377起（涉及病例1 719例）进行分析。其中，家庭聚集性疫情297起（占79%），确诊病例中位数为4例；聚餐39起（占10%），确诊病例中位数为5例；商场或超市23起（占6%），确诊病例中位数为13例；工作单位12起（占3%），确诊病例中位数为6例；交通工具6起（占2%），确诊病例中位数为6例。依聚集性病例潜伏期估计所需条件，选出325例，推测潜伏期为1~20 d，中位数为7 d，众数为4 d。此外，对国内某百货大楼聚集疫情分析结果提示本次疫情潜伏期患者可能成为传染源。"钻石公主"号邮轮聚集疫情从2月5-21日共634人被确诊感染，各类人群（国籍、年龄、性别）均易感，提示乘客年龄、无症状感染及邮轮内封闭环境可能是导致邮轮后续病例出现间歇同源暴露和人传人增殖模式的主要原因，两起典型疫情的进展清晰地展现了武汉早期病例的播散情况。因此，在疫情防控中，除隔离患者外，追踪、排查和隔离密切接触者及次级接触者至关重要；尤其对于疫区的健康人群，自我隔离是防控关键。.

As higher education struggles to catch up with the constantly shifting social climate, many modern students are being left overwhelmed by the sheer volume of choices they are being offered in a phenomenon known as the “tyranny of freedom”. This issue is exacerbated when they do not have the appropriate guidance from either their parents or universities to build their own identity and find a suitable position in a functional society. Following the innovative education trend, a few top-ranking universities have started self-designed major programs, making themselves pioneers of experimental education in the traditional university system. The purpose of this study aims at discovering how Taiwanese self-designed major students organize their study maps from human and identity capital perspectives. Fifteen research participants were recruited from the three universities providing self-designed major bachelor programs and asked to participate in a semi-structured interview. The content analysis result outlines those students as “learning nomads” who break department or field boundaries to do interdisciplinary learning with clear goals by tracing their learning resources across borders. Three crucial outcomes have been found: first, identity capital mainly influences college entrance channel choices in regards to motivation and has a minor influence on how self-designed major students arrange their learning maps. Second, in regards to human capital, modularized and self-directed learning and the arrangement of theoretical and experiential knowledge do not work alone but together. Finally, learning guidance was found to be essential under the stress of tyranny of freedom.

AIM To assess the effect of antibiotics administered in feed on the resistance phenotypes and genotypes of Escherichia coli in the chicken intestine. METHOD AND RESULTS Chickens were administered amoxicillin, chlortetracycline and florfenicol in feed and 203 intestinal E. coli were examined for their susceptibility to 11 antimicrobial agents and for the presence of antibiotic resistance genes (ARG) using PCR. DNA was extracted from chicken stool samples in 15, 20, 30 and 40 day old chickens. We found that while antibiotic resistance rates increased with time, the relative gene abundance of tet(W), tet(A), cmlA, cfr and sul1 decreased. In contrast, the relative abundance of gene blaTEM and mcr-1 increased over the experimental period. Pearson correlation analysis indicated that sul1 was correlated with tet(W) (R = 0·630, P

Investigations of anti-HIV-1 human hematopoietic stem/progenitor cell (HSPC)-based gene therapy have been performed by HIV-1 challenge after the engraftment of gene-modified HSPCs in humanized mouse models. However, the clinical application of gene therapy is to treat HIV-1-infected patients. Here, we developed a new method to investigate an anti-HIV-1 HSPC-based gene therapy in humanized mice previously infected with HIV-1. First, humanized mice were infected with HIV-1. When plasma viremia reached >107 copies/mL 3 weeks after HIV-1 infection, the mice were myeloablated with busulfan and transplanted with anti-HIV-1 gene-modified CD34+ HSPCs transduced with a lentiviral vector expressing two short hairpin RNAs (shRNAs) against CCR5 and HIV-1 long terminal repeat (LTR), along with human thymus tissue under the kidney capsule. Anti-HIV-1 vector-modified human CD34+ HSPCs successfully repopulated peripheral blood and lymphoid tissues in HIV-1 previously infected humanized mice. Anti-HIV-1 shRNA vector-modified CD4+ T lymphocytes showed selective advantage in HIV-1 previously infected humanized mice. This new method will be useful for investigations of anti-HIV-1 gene therapy when testing in a more clinically relevant experimental setting. Keywords: humanized mouse model, gene therapy for HIV/AIDS, HPSC-based gene therapy

Ubiquitin-specific protease 18 (USP18) is known as an inhibition factor and has been associated with the innate immune response to pathogens. USP18 is the only deconjugating protease with specificity for interferon-stimulated gene 15 (ISG15), which is supposed to be missing in birds. To analyze the efficacy of goose USP18 (goUSP18) against Tembusu virus (TMUV) infection, we first cloned USP18 homologous cDNA from TMUV infected geese. The coding sequence was 1131 bp, and the deduced amino acid sequence shared conserved motifs with its homologues. Tissue-specific expression has shown that goUSP18 transcripts are strongly expressed in the spleen and liver of adult geese, as well as in the pancreas of goslings. Moreover, the goUSP18 transcripts were induced by goose interferons (goIFN) in goose embryo fibroblasts (GEF) and by TLR ligands in peripheral blood mononuclear cells (PBMC). Notably, goUSP18 transcripts were highly up-regulated by TMUV infection compared to the basal level in uninfected birds. Taken together, these results suggested that goUSP18 was involved in host innate immunity against TMUV infection.

A new type of monomer complex [Ce3(L)2∙(NO3)5∙(DMF)2] was successfully synthesized by hydrothermal method. The structure of the complex was analyzed by single crystal X-ray diffraction, elemental analysis, and infrared spectroscopy. And the powder X-ray diffraction analysis was used to verify the purity of the complex. UV-vis (Ultraviolet-visible) absorption spectroscopy shows that the complex is inserted into FS-DNA (fish sperm DNA) through the interaction with DNA base pairs via hydrogen bonds, and the binding constant Kb of DNA is 9.8 × 104 M-1. Fluorescence spectroscopy experiments revealed the binding capacity of DNA, and the fluorescence quenching constant Ksv value was 0.072 × 105 M-1. Molecular docking studies have shown that the complex can be effectively inserted into the small groove of DNA. Flow cytometry analyzed the ability of the complex to induce apoptosis HeLa cells (human cervical cancer cells). This series of experiences demonstrated the potential therapeutic value of this complex.

On the basis of economic and energy-saving criteria, the minimum effective dose of ionic liquids (ILs) for the catalytic conversion of CO2 into cyclic carbonates was first explored by confinement. With one-step assembly of mesoporous silica (mSiO2) by using a fixed amount of silicon source with varying amounts of ILs as templates, certain amounts of 1-ethyl-3-methyl imidazolium bromides (EmimBr) were tailored and confined in mSiO2. The confined ILs (EmimBr@mSiO2) retained the advantages of homo- and heterogeneous catalysts, exhibiting higher performance than bulk EmimBr under identical reaction conditions. Amongst all the prepared materials, EmimBr@mSiO2 with the lowest amount of EmimBr (6.9 wt%) exhibited the biggest improvement in catalytic activity, achieving a TOF of 112.6 h−1 which is almost 1.7 times the bulk phase with good recyclability. The boosted catalytic activity could be attributed to the larger proportion of mesopores, the better dispersity of EmimBr (Si/Br = 25) and the synergistic effect from more exposed silanol groups (Si–OH/Br = 8) in the structure. The good recyclability was then explained by the XPS analysis and density functional theory (DFT) calculation, which confirmed that the compressing effect from Si–OH could enhance the cation and anion interaction to stabilize ILs in the space more firmly when less ILs were confined.

Three kinds of carbon-modified electrodes on stability of lithium metal deposition were investigated. Results indicated the amorphous carbon-modified electrode is more effective to improve initial Coulombic efficiency than the graphitized carbon-modified electrode. With high porosity (81%) and amorphous crystal structure, the low cost micro-hollow carbon fiber foam electrode provides high and stable Coulombic efficiency of 99.5% for more than 100 cycles when the areal capacity of electrode approaches 6 mAh·cm−2. The high areal capacity of high porosity electrode would be a promising anode for lithium-sulfur battery.

The effects of intensive melt shearing and Ca concentration on grain refinement of commercial purity Mg have been investigated by standard TP-1 casting tests, X-ray diffraction combined with the observation of optical microscope and scanning electron microscope. It was found that, without intensive melt shearing, Ca addition greatly improved grain structure of Mg from columnar grain to equiaxed grain. With Ca concentration increasing from 0.01 to 1 wt. %, the average grain size of the alloy gradually decreased. When intensive melt shearing was applied, the grain structures of the alloy remained equiaxed grain with Ca concentration variation. The average grain size first decreased and then kept invariable with Ca concentration increasing to 1 wt. %. The grain refining mechanism of Ca concentration variable and intensive melt shearing was discussed.

The UL13 protein of the duck enteritis virus (DEV), predicted to encode a Ser/Thr protein kinase, belongs to the family of conserved herpesvirus protein kinases (CHPK), which plays an important role in herpesvirus proliferation. In this study, truncated UL13 was expressed as a fusion protein of approximately 44 kDa using a prokaryotic expression system, and this protein was used to generate a specific anti-UL13 antibody. This antibody detected UL13 starting at 4 h post infection in duck embryonic fibroblast cells and identified UL13 to be present in both the cytoplasm and the nucleus. UL13 RNA was found to be transcribed starting at 2 h post infection, and the synthesis of the UL13 mRNA was found to be sensitive to the protein synthesis inhibitor cycloheximide (CHX) and tolerant of the DNA polymerase inhibitor ganciclovir (GCV). Its nuclear location and status as an early gene suggested that DEV UL13 might play important roles in DEV replication, which was confirmed by comparing the proliferation of a UL13-knockout mutant virus, a revertant virus, and the parent virus in cell culture. The specific mechanisms of UL13 in viral replication need to be further studied.

The low concentration Zr and intensive melt shearing effects on grain refinement of commercial purity Mg has been studied. It was found that the low concentration Zr addition, combined with intensive melt shearing, resulted in a significantly grain refinement. The mechanism of grain refinement on the intensive melt shearing dispersing MgO film into individual MgO particle and enhancing the adsorption of low concentration Zr on the surface of MgO particle was proposed.

Tumor metastasis into the central nervous system (CNS) and lymph nodes (LNs) is a major obstacle for effective therapies. Therapeutic monoclonal antibodies (mAb) have revolutionized tumor treatment; however, their efficacy for treating metastatic tumors-particularly, CNS and LN metastases-is poor due to inefficient penetration into the CNS and LNs following intravenous injection. We recently reported an effective delivery of mAb to the CNS by encapsulating the anti-CD20 mAb rituximab (RTX) within a thin shell of polymer that contains the analogs of choline and acetylcholine receptors. This encapsulated RTX, denoted as n-RTX, eliminated lymphoma cells systemically in a xenografted humanized mouse model using an immunodeficient mouse as a recipient of human hematopoietic stem/progenitor cells and fetal thymus more effectively than native RTX; importantly, n-RTX showed notable anti-tumor effect on CNS metastases which is unable to show by native RTX. As an important step toward future clinical translation of this technology, we further analyzed the properties of n-RTX in immunocompetent animals, rats, and non-human primates (NHPs). Our results show that a single intravenous injection of n-RTX resulted in 10-fold greater levels in the CNS and 2-3-fold greater levels in the LNs of RTX, respectively, than the injection of native RTX in both rats and NHPs. In addition, we demonstrate the enhanced delivery and efficient B-cell depletion in lymphoid organs of NHPs with n-RTX. Moreover, detailed hematological analysis and liver enzyme activity tests indicate n-RTX treatment is safe in NHPs. As this nanocapsule platform can be universally applied to other therapeutic mAbs, it holds great promise for extending mAb therapy to poorly accessible body compartments.