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Systemic lupus erythematosus (SLE) is a debilitating autoimmune disorder characterized by unknown pathogenesis and heterogeneous clinical manifestations. The current existing serum biomarkers for SLE have limited sensitivity or specificity, making early and precise diagnosis difficult. Here, we identified two N-glycans on serum immunoglobulin G (IgG) as excellent diagnostic biomarkers for SLE based on in-depth glycomic analyses of 389 SLE patients and 304 healthy controls. These two N-glycan biomarkers are specific for diagnosing SLE, as no significant changes in these biomarkers were observed in other systemic autoimmune diseases that are easily confused with SLE, such as rheumatoid arthritis, primary Sjögren’s syndrome, or systemic sclerosis. Notably, the two N-glycan biomarkers proved to be autoantibody-independent and all-stage patient suitable. The two N-glycan biomarkers are demonstrated to be located on the Fc region based on fragment-specific glycan analysis and glycopeptide analysis, suggesting their close correlation with disease activity. Enzyme analyses revealed dysregulation of a series of glycotransferases in SLE, which might be responsible for the observed glycan alteration. Our findings provide insights into efficient population screening based on serum IgG glycosylation and potential new pathogenic factors of SLE.

Abstract Background To establish a prognostic model to predict the overall survival (OS) in patients with unresectable hepatocellular carcinoma (HCC) treated with intensity modulated radiotherapy (IMRT). Methods The unresectable HCC patients treated with IMRT were retrospectively analyzed and randomized into development cohort (n = 237) and validation cohort (n = 103) in a 7:3 ratio. We developed a prognosis model with the multivariate Cox regression analysis in the development cohort to derive the predictive nomogram, which was then validated in the validation cohort. Model performance was evaluated by the c-index, the area under curve(AUC) and the calibration plot. Results A total of 340 patients were enrolled. Tumor numbers > 3 (HR = 1.69, 95% CI = 1.21–2.37), AFP ≥ 400 ng/ml (HR = 1.52, 95% CI = 1.10–2.10), PLT 150U/L (HR = 1.65, 95% CI = 1.15–2.37) and prior surgery (HR = 0.63, 95% CI = 0.43–0.93) were independent prognostic factors. The nomogram based on independent factors was constructed. The c-index for OS prediction was 0.658 (95% CI, 0.647–0.804) and 0.683 (95% CI, 0.580–0.785) in the development and validation cohort, respectively. The nomogram demonstrated good discriminative ability with AUC rates of 0.726, 0.739 and 0.753 at 1-year, 2-year and 3-year models in the development cohort, and 0.715, 0.756 and 0.780 in the validation cohort, respectively. Additionally, good prognostic discrimination of the nomogram is also reflected in stratifying patients into two subgroups with distinct prognosis. Conclusions We constructed a prognostic nomogram for predicting the survival of patients with unresectable HCC treated with IMRT.

ABSTRACTDermatophytic pseudomycetoma is a rare invasive infection, involving both immunocompetent and immunocompromised individuals. Since the discovery of inherited immune disorders such as the impairment of CARD9 gene, extended dermatophyte infections are mostly ascribed to any of these host factors. This study is to present and explore the potential causes in a fatal dermatophytic pseudomycetoma patient. We present a chronic and deep pseudomycetoma caused by the common dermatophyte Microsporum canis which ultimately led to the death of the patient. Mycological examination, genetic studies and host immune responses against fungi were performed to explore the potential factors. The patient had decreased lymphocyte counts with significantly reduced CD4+ T cells, although all currently known genetic parameters proved to be normal. Through functional studies, we demonstrated that peripheral blood mononuclear cells from the patient showed severe impairment of adaptive cytokine production upon fungus-specific stimulation, whereas innate immune responses were partially defective. This is, to our knowledge, the first report of fatal dermatophytic pseudomycetoma in a patient with non-HIV CD4 lymphocytopenia, which highlights the importance of screening for immune deficiencies in patients with deep dermatophytosis.

Information transparency plays a vital role for developing capital markets. Using data of A-share listed companies from 2007 to 2020, this study examined the impact of customer concentration on corporate information transparency from a supply chain perspective. It suggests that a significant negative correlation exists between customer concentration and information transparency. Customer concentration affects the quality of corporate information disclosures. Through the mechanism test, the impact of customer concentration on corporate information transparency is based on the risk effect rather than the substitution effect of private information on public information. Research on regulatory effects points out that a poor internal information environment aggravates the negative relationship between customer concentration and information transparency. However, media supervision and a higher marketization process alleviate the adverse effects of customer concentration on information transparency. This study indicates that firms with a higher customer concentration have a higher risk of information disclosure, which provides a reference point for investors for making investment-related decisions and for the capital market supervision department for formulating information disclosure policies.

The performance of ethylene/1-octene copolymer primarily depends on the microstructure of the polymer chain. This study employed a new method to control the inter-distribution of hexyl chain branches directly on the backbone of the ethylene/1-octene copolymer. Three ethylene/1-octene copolymers with different inter-distributions of hexyl chain branches were synthesized using [Me2Si(C5Me4) (NtBu)] TiCl2 (Ti–CGC) by different feeding sequences in the semi-continuous polymerization reaction system. The three copolymers were named according to the feeding sequence of the materials: ethylene/1-octene/Ti–CGC (EOC), 1-octene/Ti–CGC/ethylene (OCE), and ethylene/Ti–CGC/1-octene (ECO), respectively. The structure and properties of the copolymers were characterized using HT-GPC, 13C-NMR, DSC, WAXD, DMA, MI, and Uniaxial Tension Test. The results showed that the feeding sequence greatly affected the comonomer distribution of the molecular chains, molecular weight, molecular weight distribution, and chemical composition of the copolymers, consequently influencing their thermal performance and mechanical properties. Thus, it is probable that one could obtain an ethylene/1-octene copolymer with designed properties by controlling the feeding sequence during the ethylene/1-octene semi-continuous copolymerization process.

Abstract A dual P‐layer 4H‐SiC p‐i‐n ultraviolet photodetector is proposed and studied. The modeling results of the photoelectric characteristics demonstrate the dual P‐layer structure could effectively reduce the recombination of the photogenerated carriers and separate more electron‐hole pairs near the surface of the device. And, the photodetector exhibits a significantly high response and detectivity, especially in the wavelength range of extreme ultraviolet to ultraviolet‐C. A high spectral response peak of 0.2 A/W corresponding to a quantum efficiency of 95.3% is achieved. Furthermore, an avalanche breakdown voltage as low as 182 V is observed. The dual P‐layer structure significantly presents an innovative approach for the advancement of future ultraviolet photodetectors applied in the detection at illumination wavelengths ranging from extreme ultraviolet to ultraviolet‐A.

In this paper, an optimal sliding mode control method for trajectory tracking of discrete-time systems based on linear quadratic regulator is proposed to improve the trajectory tracking control accuracy and robustness of upper limb rehabilitation robot under the condition of highly nonlinearities, external disturbances, and unmodeled dynamics. Firstly, considering the uncertainty of the mass and moment of inertia of the connecting rod arm of the upper limb rehabilitation robot and the uncertainty of external interference, the dynamic model of the upper limb rehabilitation robot is established by using the Euler Lagrange method, and the linear time-varying state equation of the rehabilitation robot system under the influence of both nonlinear and uncertain factors is derived. Secondly, directing at the chattering problem in sliding mode control, a sliding mode control method based on a new discrete time reaching law is designed to reduce the amplitude of chattering in the control input signal of the upper limb rehabilitation robot system and improve the tracking speed. Furthermore, combined with linear quadratic optimal control, the optimal discrete integral sliding mode control law (LQRSMC) is finally obtained. Meanwhile, for the sake of reducing the influence of the uncertain signal on the system, a robust control law is adopted to estimate and compensate the uncertain interference. The stability of the upper limb rehabilitation robot system is verified by the sliding mode approach condition of the discrete system. Finally, the genetic algorithm is used to further optimize the weighted value, and MATLAB/Simulink is used to simulate the state trajectory of the upper limb rehabilitation robot under various weighted values. The control strategy can not only effectively weaken the trajectory tracking oscillation problem of the upper limb rehabilitation robot, but also overcome the external disturbance and modeling uncertainty, while ensuring the robustness of the rehabilitation robot system.

The authors developed a methodology for bulk enrichment of antigen-specific B cells to improve the diversity of antibody sequences and increase the number of functional antigen-specific antibodies coming from different antibody generation platforms.

The heat rejected by outdoor units of split A/C conditioners can impact the ambient outdoor environment of mixed-mode buildings. Nevertheless, how this environmental impact may affect the space-conditioning energy use and indoor air pollution is poorly understood. By coupling EnergyPlus and Fluent, this study examines the effects of outdoor units’ heat rejection on the building surroundings, building cooling load, and indoor PM2.5 exposure of a six-storey mixed-mode building. The building had an open-plan room on each floor, with the outdoor unit positioned below the window. The coupled model was run for a selected day when the building was cooled by air conditioning and natural ventilation. Five mixed-mode cooling strategies were simulated, reflecting different window-opening schedules, airflow rates of outdoor units, and cooling set-points. The results indicate that compared with the always-air-conditioned mode, the mixed-mode operation could significantly mitigate the negative impact of heat rejection on space-cooling energy consumption. Increasing the airflow rate of outdoor units led to a lower increase in demand for space cooling and lower indoor PM2.5 exposure. If one of the six rooms needs to be cooled to a lower temperature than the others; choosing the bottom-floor room helped achieve more energy savings and better indoor air quality.

In recent years, there have been numerous studies on the application of retroreflective (RR) materials to exterior building walls to relieve the urban heat island (UHI) phenomenon and save building energy consumption instead of diffuse highly reflective (DHR) materials. Experimental measurements were undertaken to investigate the impact of applying DHR and RR materials to building exterior walls on the outdoor thermal environment. DHR and RR walls were tested with three canyon aspect ratios (H/ D) of 0.5, 1.0, and 1.5, respectively, with seven environmental indexes recorded and compared, including air temperature (Ta), relative humidity (RH), sol-air temperature (SAT), operative temperature (OT), standard effective temperature (SET*), change in operative temperature (COT), and real-time solar reflectance (ρ). The results show that the RR wall is more effective in improving the outdoor thermal environment, where SAT decreased by 4.5 °C, SET* decreased by 0.5 °C, and COT decreased by 1.2 °C, on average, while it can also improve the real-time solar reflectance (ρ) by 12% on average compared to the DHR wall. Moreover, it gets more effective in scenarios with a higher canyon aspect ratio.

Abstract Rheumatoid arthritis (RA) is an aggressive autoimmune arthritis, and current therapies remain unsatisfactory due to low remission rate and substantially adverse effects. Low-dose interleukin-2 (Ld-IL2) is potentially a therapeutic approach to further improve the disease. This randomized, double-blind, placebo-controlled trial was undertaken to evaluate the efficacy and safety of Ld-IL2 in patients with active RA. Patients were randomly assigned (1:1) to receive Ld-IL2, defined as a dose of 1 million IU, or placebo in a 12-week trial with a 12-week follow-up. Three cycles of Ld-IL2 or placebo were administered subcutaneously every other day for 2 weeks (a total of 7 doses), followed by a 2-week break. All patients received a stable dose of methotrexate (MTX). The primary outcomes were the proportion of patients achieving the ACR20, DAS28-ESR

Exterior shading devices and outdoor units can be closely coupled since these two building components are commonly installed next to each other. This study uses a coupled EnergyPlus-Fluent modeling approach to examine how a combination of exterior shading and heat rejection from outdoor units can affect the ambient outdoor environment of a building, and how changes in the ambient outdoor environment can influence cooling loads and indoor PM2.5 exposure. Three exterior shading devices were simulated, including horizontal overhangs, vertical overhangs, and vertical fins. Data from wind-tunnel experiments and field measurements were used to ensure the accuracy of the airflow model, energy model, and pollution model developed in this study. Results indicate that horizontal overhangs could almost offset the increase in cooling loads due to increased ambient outdoor temperatures caused by heat rejection. The use of vertical overhangs did not always mean lower demand for space cooling when heat rejection was considered. Heat rejection, horizontal overhangs, and vertical overhangs could help reduce indoor PM2.5 exposure, while indoor air pollution was worse after the implementation of vertical fins. This study shows how exterior shading devices and outdoor units can be coupled to achieve better building energy efficiency and improved occupant health.

BackgroundTranexamic acid (TXA) has been used in posterior lumbar interbody fusion (PLIF) and reduces blood loss. However, it has not been reported whether it will continue to affect postoperative red blood cells (RBC), hemoglobin (HB), hematocrit (HCT), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). The purpose of this study was to observed the above indicators at different time after PLIF with unit dose intravenous (iv) TXA.MethodsThe data of 44 patients treated by single-segment PLIF from 2020.11 to 2022.3 were retrospectively analyzed. Observation group was given a unit dose of ivTXA (1 g/100 mL) 15 min before skin incision after general anesthesia. Patients without TXA were recorded as control group. Main observation indicators include RBC, HB, HCT, CRP and ESR on the 1st, 4th, 7th and last tested day after surgery. Secondary observation indicators include postoperative activated partial thrombin time (APTT), prothrombin time (PT), thrombin time (TT), and fibrinogen (FIB); and operation time, intraoperative blood loss, postoperative drainage volume, incision healing, postoperative deep vein thrombosis and postoperative hospital stay.ResultsThe operation was successfully completed without related complications. At term of main observation indicators, RBC, HB and HCT remained relatively stable, while CRP and ESR fluctuated to some extent after PLIF. The RBC, HB and HCT in the observation group were higher than those in the control group with statistically significant (p 0.05). At term of secondary observation indicators, the intraoperative blood loss and postoperative drainage volume of the observation group were lower than those of the control group with statistically significant (p 0.05).ConclusionThe application of unit dose of ivTXA in PLIF can safely and effectively reduce blood loss. Meanwhile, it can also maintain higher RBC, HB, HCT levels without disturbing CRP and ESR levels after surgery.

Abstract Objective To investigate the regulation of T follicular regulatory (Tfr) and T follicular (Tfh) cell subtypes by low-dose IL-2 in systemic lupus erythematosus (SLE) in a randomized, double-blind, placebo-controlled clinical trial. Methods A post hoc analysis was performed in a randomized cohort of SLE patients (n=60) receiving low-dose IL-2 therapy (n=30) or placebo (n=30), along with the standard of care treatment. The primary endpoint was the attainment of SLE responder index-4 (SRI-4) at week 12 in the trial. Twenty-three healthy controls were enrolled for T cell subset detection at the same time as the trial. The t-stochastic neighbor embedding (tSNE) analysis of CD4 T subsets based on immune cells flow cytometry markers was performed to distinguish Tfh, Tfh1, Tfh2, Tfh17, and Tfr cell subsets. Results Compared with HC, the frequency of Tfr (CXCR5+PD-1low Treg and CXCR5+PD-1high Treg) cells was significantly reduced, while the pro-inflammatory Tfh cells were increased in patients with SLE. The imbalanced Tfh cell was associated with several pathogenic factors (anti-dsDNA antibodies (r=0.309, P=0.027) and serum IL-17 (r=0.328, P=0.021)) and SLE Disease Activity Index (SLEDAI) score (r=0.273, P=0.052). Decreased CXCR5+PD-1low Treg/Tfh and CXCR5+PD-1low Treg/Tfh17 were both associated with increased immunoglobulin M (IgM) (r=−0.448, P=0.002 and r=−0.336, P=0.024, respectively). Efficacy of low-dose IL-2 therapy was associated with a restored Tfr/Tfh cell balance. Conclusion These data support the hypothesis that promotion of Tfr is associated with decreased disease activities and that low-dose IL-2 therapy can recover Tfr/Tfh immune balance. Trial registration number ClinicalTrials.gov Registries ( NCT02465580 ).

Abstract Accumulating evidence has implicated dietary factors as important risks for rheumatoid arthritis (RA) development, but analyses of the effects of red meat consumption on RA have yielded diverging results. The aim of this study was to explore the association between red meat and RA in a large-scale, cross-sectional study. From June to December 2016, a total of 733 patients were investigated, from which 707 participants were included in the analysis. These patients were divided into two groups according to their consumption of red meat (

To effectively suppress the horizontal vibration of a high-speed elevator car caused by uncertainties such as the irregularity of guide rails and the piston wind in the hoistway, this paper proposes a new variable universe fuzzy control method for semi-active guide shoes with magnetorheological (MR) dampers based on the firefly algorithm and backpropagation (FA-BP) algorithm fuzzy neural network (FNN). First, the dynamic model of a car system is constructed, and the FNN system based non-parametric model of the MR damper is established with the original MR damper data collected from experiments. Then, a variable universe fuzzy main controller is presented to control the input current of the MR damper. As for its variable universe contraction-expansion factors, another FNN auxiliary controller is designed to accurately adjust the universe. Furthermore, the FA-BP algorithm is utilized to train the FNN auxiliary controller. Finally, the elevator experiment is carried out to analyze the characteristics of horizontal vibration, and simulation tests are conducted using the measured excitation signal and two kinds of simulated excitation signals, respectively. The results show that the proposed controller has a lower horizontal vibration acceleration, tilt angle acceleration and other index values than the passive controller or the FNN controller, indicating that the proposed control method can effectively suppress the horizontal vibration of a high-speed elevator. This study can provide the technical foundation for intelligent vibration control of high-speed elevators.

Cytoplasmic male sterility (CMS) lays a foundation for the utilization of heterosis in soybean. The soybean CMS line SXCMS5A is an excellent CMS line exhibiting 100% male sterility. Cytological analysis revealed that in SXCMS5A compared to its maintainer SXCMS5B, its tapetum was vacuolated and abnormally developed. To identify the genes and metabolic pathways involving in pollen abortion of SXCMS5A, a comparative transcriptome analysis was conducted between SXCMS5A and SXCMS5B using flower buds. A total of 372,973,796 high quality clean reads were obtained from 6 samples (3 replicates for each material), and 840 differentially expressed genes (DEGs) were identified, including 658 downregulated and 182 upregulated ones in SXCMS5A compared to SXCMS5B. Among them, 13 DEGs, i.e., 12 open reading frames (ORFs) and 1 COX2, were mitochondrial genome genes in which ORF178 and ORF103c were upregulated in CMS lines and had transmembrane domain(s), therefore, identified as CMS candidate mitochondrial genes of SXCMS5A. Furthermore, numerous DEGs were associated with pollen wall development, carbohydrate metabolism, sugar transport, reactive oxygen species (ROS) metabolism and transcription factor. Some of them were further confirmed by quantitative real time PCR analysis between CMS lines with the same cytoplasmic source as SXCMS5A and their respective maintainer lines. The amount of soluble sugar and adenosine triphosphate and the activity of catalase and ascorbic acid oxidase showed that energy supply and ROS scavenging decreased in SXCMS5A compared to SXCMS5B. These findings provide valuable information for further understanding the molecular mechanism regulating the pollen abortion of soybean CMS.

High-quality data on building energy use and indoor pollution are critical to supporting government efforts to reduce carbon emissions and improve the population’s health. This study describes the development of a city-representative housing stock model used for estimating space-cooling energy use and indoor PM2.5 exposure across the Hong Kong housing stock. Archetypes representative of Hong Kong dwellings were developed based on geographically-referenced housing databases. Simulations of unique combinations of archetype, occupation, and environment were run using EnergyPlus, estimating the annual space-cooling energy consumption and annual average PM2.5 exposure concentrations under both non-retrofit and retrofit scenarios. Results show that modern village houses and top-floor flats in high-rise residential buildings, on average, used 19% more space-cooling energy than other archetypes. Dwellings in urban areas had lower exposure to outdoor-sourced PM2.5 and higher exposure to indoor-sourced PM2.5 compared to those in rural areas. The percentage decrease in space-cooling energy consumption caused by energy efficiency retrofits, including external wall insulation, low-e windows, and airtightening, varied significantly based on archetype. The implementation of external wall insulation in the housing stock led to an average decrease of 3.5% in indoor PM2.5 exposure, whilst airtightening and low-e windows resulted in 7.9% and 0.2% average increases in exposure, respectively.

The heating, ventilation, and air conditioning (HVAC) system is a major energy consumer in office buildings, and its operation is critical for indoor thermal comfort. While previous studies have indicated that reinforcement learning control can improve HVAC energy efficiency, they did not provide enough information about end-to-end control (i.e., from raw observations to ready-to-implement control signals) for centralized HVAC systems in multizone buildings due to the limitations of reinforcement learning methods or the test buildings being single zones with independent HVAC systems. This study developed a model-free end-to-end dynamic HVAC control method based on a recently proposed deep reinforcement learning framework to control the centralized HVAC system of a multizone office building. By using the deep neural network, the proposed control method could directly take measurable parameters, including weather and indoor environment conditions, as inputs and control indoor temperature setpoints at a supervisory level. In some test cases, the proposed control method could successfully learn a dynamic control policy to reduce HVAC energy consumption by 12.8% compared with the baseline case using conventional control methods, without compromising thermal comfort. However, an over-fitting problem was noted, indicating that future work should first focus on the generalization of deep reinforcement learning.

Objectives To develop a model of in-hospital mortality using medical record front page (MRFP) data and assess its validity in case-mix standardisation by comparison with a model developed using the complete medical record data.Design A nationally representative retrospective study.Setting Representative hospitals in China, covering 161 hospitals in modelling cohort and 156 hospitals in validation cohort.Participants Representative patients admitted for acute myocardial infarction. 8370 patients in modelling cohort and 9704 patients in validation cohort.Primary outcome measures In-hospital mortality, which was defined explicitly as death that occurred during hospitalisation, and the hospital-level risk standardised mortality rate (RSMR).Results A total of 14 variables were included in the model predicting in-hospital mortality based on MRFP data, with the area under receiver operating characteristic curve of 0.78 among modelling cohort and 0.79 among validation cohort. The median of absolute difference between the hospital RSMR predicted by hierarchical generalised linear models established based on MRFP data and complete medical record data, which was built as ‘reference model’, was 0.08% (10th and 90th percentiles: −1.8% and 1.6%). In the regression model comparing the RSMR between two models, the slope and intercept of the regression equation is 0.90 and 0.007 in modelling cohort, while 0.85 and 0.010 in validation cohort, which indicated that the evaluation capability from two models were very similar.Conclusions The models based on MRFP data showed good discrimination and calibration capability, as well as similar risk prediction effect in comparison with the model based on complete medical record data, which proved that MRFP data could be suitable for risk adjustment in hospital performance measurement.

In order to effectively suppress horizontal vibration of the ultra-high-speed elevator car system. Firstly, considering the nonlinearity of guide shoe, parameter uncertainties, and uncertain external disturbances of the elevator car system, a more practical active control model for horizontal vibration of the 4-DOF ultra-high-speed elevator car system is constructed and the rationality of the established model is verified by real elevator experiment. Secondly, a predictive sliding mode controller based on adaptive fuzzy (PSMC-AF) is proposed to reduce the horizontal vibration of the car system, the predictive sliding mode control law is achieved by optimizing the predictive sliding mode performance index. Simultaneously, in order to decrease the influence of uncertainty of the car system, a fuzzy logic system (FLS) is designed to approximate the compound uncertain disturbance term (CUDT) on-line. Furthermore, the continuous smooth hyperbolic tangent function (HTF) is introduced into the sliding mode switching term to compensate the fuzzy approximation error. The adaptive laws are designed to estimate the error gain and slope parameter, so as to increase the robustness of the system. Finally, numerical simulations are conducted on some representative guide rail excitations and the results are compared to the existing solution and passive system. The analysis has confirmed the effectiveness and robustness of the proposed control method.

Hybridoma technology has been valuable in the development of therapeutic antibodies. More recently, antigen-specific B-cell selection and display technologies are also gaining importance. A major limitation of these approaches used for antibody discovery is the extensive process of cloning and expression involved in transitioning from antibody identification to validating the function, which compromises the throughput of antibody discovery. In this study, we describe a process to identify and rapidly re-format and express antibodies for functional characterization. We used two different approaches to isolate antibodies to five different targets: 1) flow cytometry to identify antigen-specific single B cells from the spleen of immunized human immunoglobulin transgenic mice; and 2) panning of phage libraries. PCR amplification allowed recovery of paired VH and VL sequences from 79% to 96% of antigen-specific B cells. All cognate VH and VL transcripts were formatted into transcription and translation compatible linear DNA expression cassettes (LEC) encoding whole IgG or Fab. Between 92% and 100% of paired VH and VL transcripts could be converted to LECs, and nearly 100% of them expressed as antibodies when transfected into Expi293F cells. The concentration of IgG in the cell culture supernatants ranged from 0.05 µg/ml to 145.8 µg/ml (mean = 18.4 µg/ml). Antigen-specific binding was displayed by 78–100% of antibodies. High throughput functional screening allowed the rapid identification of several functional antibodies. In summary, we describe a plasmid-free system for cloning and expressing antibodies isolated by different approaches, in any format of choice for deep functional screening that can be applied in any research setting during antibody discovery.

Objective: Recent studies on double negative B cells (DN B cells) suggested that they have potential pathogenic roles in systemic lupus erythematosus (SLE). This study aimed to determine the circulating DN B cells in SLE patients and analyzed the clinical significance of this cell subset.Methods: Fifty-seven SLE patients and fifty healthy controls (HCs) were recruited in this study. Among the 57 SLE patients, 25 had lupus nephritis (LN). All patients were followed up for 24 weeks. Peripheral B cell subsets were analyzed by flow cytometry.Results: DN B cells were significantly elevated in the SLE patients, especially in the patients with LN (p < 0.01). DN B showed a positive correlation with 24-h urine protein excretion (24 h-UPE) levels (r = 0.444, p = 0.034) in LN patients, and inversely correlated with evaluated glomerular filtration rate (eGFR) (r = −0.351, p = 0.011). DN B cells had a positive correlation with plasma cells (r = 0.484, p < 0.001) and memory B cells (r = 0.703, p < 0.001). After treatment, decreased DN B cells were associated with LN alleviation (p = 0.002). In the follow-up, the remission rate of LN patients with decreased DN B cells was significantly higher than LN patients with increased DN B cells (83.33 vs. 25.00%, p = 0.030) at week 24.Conclusions: This study suggests that the peripheral DN B cells are positively correlated with the severity of renal damage in LN patients and may potentially be used as a prognostic marker in LN.

No Abstract

Brackish water is a potential fresh water resource with lower salt content than seawater. Desalination of brackish water is an important option to alleviate the prevalent water crisis around the world. As a membrane technology ranging between UF and RO, NF can achieve the partial desalination via size exclusion and charge exclusion. So, it has been widely concerned and applied in treatment of brackish water during the past several decades. Hereon, an overview of the progress in research on and application of NF technology for brackish water treatment is provided. On the basis of expounding the features of brackish water, the factors affecting NF efficiency, including the feed water characteristics, operating conditions and NF membrane properties, are analyzed. For the ubiquitous membrane fouling problem, three preventive fouling control strategies including feed water pretreatment, optimization of operating conditions and selection of anti-fouling membranes are summarized. In addition, membrane cleaning methods for restoring the fouled membrane are discussed. Furthermore, the combined utilization of NF with other membrane technologies is reviewed. Finally, future research prospects are proposed to deal with the current existing problems. Lessons gained from this review are expected to promote the sustainable development of brackish water treatment with NF technology.

This paper aims to empirically analyze the herd behavior in the VC market in the context of China, including the existence, causes and consequences of herding among venture capitalists. For our empirical analysis, we first construct a herding measure and confirm the existence of herd behavior in the Chinese VC market. Then, we perform OLS/logit regression to examine the causes and consequences of herding among venture capitalists. Our results suggest that herd behavior in the venture capital market are driven by positive signals of essential information and a higher degree of information uncertainty. However, we find no evidence of the influence of feedback trading signals on herding among venture capitalists. Further analysis suggests that a better external information environment would help weaken the herding among venture capitalists, while their reputation concerns might amplify the herding effect. Finally, we examine the economic consequence of the herding and find that the herd behavior of venture capitalists would have an adverse effect on their exit performance. In addition to the enrichment and development of herding theory, our study also provides an essential theoretical frame and policy implications for the steady growth of the venture capital market in emerging economies.

Summary: Induction of broadly neutralizing antibodies (bnAbs) that target HIV-1 envelope (Env) is a goal of HIV-1 vaccine development. A bnAb target is the Env third variable loop (V3)-glycan site. To determine whether immunization could induce antibodies to the V3-glycan bnAb binding site, we repetitively immunized macaques over a 4-year period with an Env expressing V3-high mannose glycans. Env immunizations elicited plasma antibodies that neutralized HIV-1 expressing only high-mannose glycans—a characteristic shared by early bnAb B cell lineage members. A rhesus recombinant monoclonal antibody from a vaccinated macaque bound to the V3-glycan site at the same amino acids as broadly neutralizing antibodies. A structure of the antibody bound to glycan revealed that the three variable heavy-chain complementarity-determining regions formed a cavity into which glycan could insert and neutralized multiple HIV-1 isolates with high-mannose glycans. Thus, HIV-1 Env vaccination induced mannose-dependent antibodies with characteristics of V3-glycan bnAb precursors. : Most bnAb epitopes on HIV-1 Envelope include host glycans, but previous Env vaccines have not induced glycan-dependent antibodies. Saunders et al. describe here the ontogeny, crystal structure with glycan, and virion Man9GlcNAc2-dependent neutralization for glycan-reactive antibodies induced by envelope vaccination. Keywords: HIV, V3 glycan, vaccination, glycan, long-term immunization

Primary Sjögren’s syndrome (pSS) is a chronic autoimmune disease characterized by lymphocytic infiltration of exocrine glands. Due to the absence of specific clinical manifestations and biomarkers in the early stage, pSS is generally underrecognized. To elucidate the role of the tissue-specific autoantibodies (TSAs), i.e., anti-CA6, anti-SP1, and anti-PSP antibodies, we enrolled 137 pSS patients, 32 secondary Sjögren’s syndrome (sSS) patients, and 127 healthy controls (HCs), whose serum and saliva samples were collected. TSA levels were detected by ELISA, and the clinical and laboratory data was reviewed from the medical records. The analysis results showed the following: (1) Compared to HCs, the serum IgA levels of anti-CA6, anti-SP1 and anti-PSP were significantly higher in pSS as well as in sSS patients, and anti-CA6 IgG was also notably higher in pSS patients. (2) The positivity of anti-CA6, anti-PSP and all the three antibodies together were significantly increased in anti-SSA-negative pSS patients. (3) The average IgM levels of anti-CA6 and anti-SP1 decreased as the disease duration extended. (4) The anti-CA6-positive patients have significantly higher levels of serum IgA, while the anti-PSP-positive group has a notably higher serum IgM level. (5) Another autoantibody specific to the salivary glands, anti-α-fodrin antibody, was elevated in TSA-positive patients, especially in the anti-CA6-positive group. (6) Preliminary detection of saliva TSAs showed that all the IgG levels of these three antibodies increased significantly in pSS patients. In conclusion, TSAs improve diagnosis of pSS in the early stage, especially in anti-SSA-negative patients, and their tissue-specific nature indicates localized salivary injury, which deserves further studies to clarify the mechanism.

Infection of African green monkeys with simian immunodeficiency virus is a potential model for HIV vaccine development. Here, Zhang et al. catalogue the immunoglobulin loci present in the genome of these animals, and experimentally study their B-cell response to the viral envelope protein.

HIV-1 mucosal transmission begins with virus or virus-infected cells moving through mucus across mucosal epithelium to infect CD4+ T cells. Although broadly neutralizing antibodies (bnAbs) are the type of HIV-1 antibodies that are most likely protective, they are not induced with current vaccine candidates. In contrast, antibodies that do not neutralize primary HIV-1 strains in the TZM-bl infection assay are readily induced by current vaccine candidates and have also been implicated as secondary correlates of decreased HIV-1 risk in the RV144 vaccine efficacy trial. Here, we have studied the capacity of anti-Env monoclonal antibodies (mAbs) against either the immunodominant region of gp41 (7B2 IgG1), the first constant region of gp120 (A32 IgG1), or the third variable loop (V3) of gp120 (CH22 IgG1) to modulate in vivo rectal mucosal transmission of a high-dose simian-human immunodeficiency virus (SHIV-BaL) in rhesus macaques. 7B2 IgG1 or A32 IgG1, each containing mutations to enhance Fc function, was administered passively to rhesus macaques but afforded no protection against productive clinical infection while the positive control antibody CH22 IgG1 prevented infection in 4 of 6 animals. Enumeration of transmitted/founder (T/F) viruses revealed that passive infusion of each of the three antibodies significantly reduced the number of T/F genomes. Thus, some antibodies that bind HIV-1 Env but fail to neutralize virus in traditional neutralization assays may limit the number of T/F viruses involved in transmission without leading to enhancement of viral infection. For one of these mAbs, gp41 mAb 7B2, we provide the first co-crystal structure in complex with a common cyclical loop motif demonstrated to be critical for infection by other retroviruses.

During the recent H1N1 influenza pandemic, excess morbidity and mortality was seen in young but not older adults suggesting that prior infection with influenza strains may have protected older subjects. In contrast, a history of recent seasonal trivalent vaccine in younger adults was not associated with protection.To study hemagglutinin (HA) antibody responses in influenza immunization and infection, we have studied the day 7 plasma cell repertoires of subjects immunized with seasonal trivalent inactivated influenza vaccine (TIV) and compared them to the plasma cell repertoires of subjects experimentally infected (EI) with influenza H3N2 A/Wisconsin/67/2005. The majority of circulating plasma cells after TIV produced influenza-specific antibodies, while most plasma cells after EI produced antibodies that did not react with influenza HA. While anti-HA antibodies from TIV subjects were primarily reactive with single or few HA strains, anti-HA antibodies from EI subjects were isolated that reacted with multiple HA strains. Plasma cell-derived anti-HA antibodies from TIV subjects showed more evidence of clonal expansion compared with antibodies from EI subjects. From an H3N2-infected subject, we isolated a 4-member clonal lineage of broadly cross-reactive antibodies that bound to multiple HA subtypes and neutralized both H1N1 and H3N2 viruses. This broad reactivity was not detected in post-infection plasma suggesting this broadly reactive clonal lineage was not immunodominant in this subject.The presence of broadly reactive subdominant antibody responses in some EI subjects suggests that improved vaccine designs that make broadly reactive antibody responses immunodominant could protect against novel influenza strains.

Broadly neutralizing antibodies are not commonly produced in HIV-1 infected individuals nor by experimental HIV-1 vaccines. When these antibodies do occur, it is important to be able to isolate and characterize them to provide clues for vaccine design. CAP206 is a South African subtype C HIV-1-infected individual previously shown to have broadly neutralizing plasma antibodies targeting the envelope gp41 distal membrane proximal external region (MPER). We have now used a fluoresceinated peptide tetramer antigen with specific cell sorting to isolate a human neutralizing monoclonal antibody (mAb) against the HIV-1 envelope gp41 MPER. The isolated recombinant mAb, CAP206-CH12, utilized a portion of the distal MPER (HXB2 amino acid residues, 673-680) and neutralized a subset of HIV-1 pseudoviruses sensitive to CAP206 plasma antibodies. Interestingly, this mAb was polyreactive and used the same germ-line variable heavy (V(H)1-69) and variable kappa light chain (V(K)3-20) gene families as the prototype broadly neutralizing anti-MPER mAb, 4E10 (residues 672-680). These data indicate that there are multiple immunogenic targets in the C-terminus of the MPER of HIV-1 gp41 envelope and suggests that gp41 neutralizing epitopes may interact with a restricted set of naive B cells during HIV-1 infection.

A component to the problem of inducing broad neutralizing HIV-1 gp41 membrane proximal external region (MPER) antibodies is the need to focus the antibody response to the transiently exposed MPER pre-hairpin intermediate neutralization epitope. Here we describe a HIV-1 envelope (Env) gp140 oligomer prime followed by MPER peptide-liposomes boost strategy for eliciting serum antibody responses in rhesus macaques that bind to a gp41 fusion intermediate protein. This Env-liposome immunization strategy induced antibodies to the 2F5 neutralizing epitope ⁶⁶⁴DKW residues, and these antibodies preferentially bound to a gp41 fusion intermediate construct as well as to MPER scaffolds stabilized in the 2F5-bound conformation. However, no serum lipid binding activity was observed nor was serum neutralizing activity for HIV-1 pseudoviruses present. Nonetheless, the Env-liposome prime-boost immunization strategy induced antibodies that recognized a gp41 fusion intermediate protein and was successful in focusing the antibody response to the desired epitope.

When tower cranes are applied in coastal engineering, the wind-induced vibration under complex wind loads along the coast will be exceptionally obvious. It is increasingly important to explore the wind-induced vibration characteristics of different sections of tower cranes under full wind angles. This paper first establishes a three-dimensional numerical wind tunnel model that can be used for the simulation of tower cranes under full wind angles and analyzes the aerodynamic load variation of the tower crane under full wind angles. Secondly, the tower crane structure is divided into sub-regions, and the AR model method in the linear filtering method is used to simulate the three-dimensional wind speed time history. Further, the wind speed time history is applied to the finite element transient analysis, and based on the Newmark-β method, the acceleration and displacement responses of different sections of the tower crane structure under fluctuating wind are systematically studied. Finally, the equivalent static wind load of different sections of the tower crane is evaluated by using the gust load factor method. The results indicate that the wind load of the tower crane exhibits an obvious three-dimensional effect, and the crosswind load cannot be ignored in the analysis of wind stability. The different sections of the tower crane structure show low-frequency vibration characteristics, and the low-frequency band is dominated by down-wind vibration, while the high-frequency band often experiences crosswind vibration. The amplification effect of the tower crane on fluctuating wind loads will increase with the increase of the height of the tower crane and the length of the jib, and the amplification effect on fluctuating wind loads in the crosswind direction is more obvious. The equivalent static wind load on the top of the tower crane reaches the maximum when the angle between the jib and the incoming wind is 60◦ . [ABSTRACT FROM AUTHOR]