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Aim: This study adopted a three‐wave random intercept cross‐lagged panel model to explore the longitudinal reciprocal relationships between (a) the teacher–student relationship (TSR) quality and (b) the parent–child relationship (PCR) quality and positive affect among Chinese primary school students. Samples: Two primary school student samples, including 3505 and 2505 students, were tracked with their perceived relationship quality with math teachers and parents and their positive affect levels in mathematics learning over three academic years. Results: The results demonstrated that more closeness with parents could significantly predict students' subsequent higher level of positive affect in mathematics learning. However, more closeness with their math teachers did not show significant prediction. Meanwhile, more conflict with math teachers and parents could significantly predict their subsequent lower degree of perceived positive affect in mathematics learning. That is, a reciprocal association lines in the PCR quality and positive affect, whereas only a unidirectional association exists between the TSR and positive affect. The predictions of the experienced positive affect on their perceived interpersonal relationships with math teachers and parents were stronger than those in the reverse association. Conclusions: This study identifies that while the effects of closeness with math teachers and parents on positive affect in students' math learning differ, conflict with math teachers and parents indeed harms students' experienced positive affect in math learning. More attention should also be paid to fostering positive affect in math learning. [ABSTRACT FROM AUTHOR]

Clipping management, which alters vegetation conditions by removing aboveground vegetation while preserving the underground root system, directly impacts hydrological processes and flow dynamics, ultimately affecting soil erosion processes. This study conducted field experiments (2 × 6 m) encompassing four clipping intensities (with vegetation coverage of 70%, 50%, 25%, and 0%), three rainfall intensities (60, 90, and 120 mm·h−1), and three slope gradients (10°, 20°, and 30°). The results showed that clipping treatments significantly reduced the Darcy–Weisbach resistance coefficient (f). Elevated levels of clipping intensity, rainfall intensity, and slope gradient led to increased flow velocity (v), Reynolds number (Re), and stream power (ω). The shear stress (τ) exhibited an upward trend with rising slope and rainfall intensity, with no significant difference in the effect of clipping intensity. Variation partitioning analysis demonstrated that the influence of steep slopes amplified the effects of rainfall intensity while diminishing the impact of clipping intensity on v values. Critically, the Bayesian network model suggested that, in comparison to the influence of raindrop splashing, soil detachment and transportation by runoff were the predominant driving mechanisms for erosion on slopes with clipped vegetation. Rainfall intensity and clipping intensity were found to raise the runoff depth and enhance the v value, which ultimately influenced soil erosion. Overall, these results contribute to an improved comprehension of the hydraulic dynamics of soil erosion on slopes with clipped vegetation and provide invaluable perspectives for developing effective clipping management strategies to ensure sustainable land utilization and judicious water resource governance. [ABSTRACT FROM AUTHOR]

Amidst the COVID‐19 pandemic, uncertainty persists among caregivers regarding the vaccination of pediatric liver transplant recipients (PLTRs). This study evaluates the immunogenicity and safety of COVID‐19 vaccination in this vulnerable population. A cohort of 30 PLTRs underwent sequential vaccinations with an inactivated SARS‐CoV‐2 vaccine followed by an Ad5‐nCoV booster. We collected and analyzed blood samples pre‐vaccination and four weeks post‐vaccination to quantify antibody and IGRA (IFN‐γ Release Assay) levels. We also documented any adverse reactions occurring within seven days post‐vaccination and monitored participants for infections over six months post‐vaccination, culminating in a comprehensive statistical analysis. The Ad5‐nCoV booster substantially elevated IgG (T1: 18.01, 20%; T2: 66.61, 55%) and nAb (T1: 119.29, 8%; T2: 3799.75, 80%) levels, as well as T‐cell responses, in comparison to the initial dose. The first dose was associated with some common adverse reactions, such as injection site pain (13.3%) and fever (16.6%), but a low rate of systemic reactions (16.0%). There was no significant difference in Omicron infection rates or RTPCR conversion times between vaccinated and unvaccinated groups. Notably, following Omicron infection, vaccinated individuals exhibited significantly higher SARS‐CoV‐2 IgG and nAb titers (average IgG: 231.21 vs. 62.09 S/CO, p = 0.0003; nAb: 5246.11 vs. 2592.07 IU/mL, p = 0.0002). The use of inactivated vaccines followed by an Ad5‐nCoV booster in PLTRs is generally safe and elicits a robust humoral response, albeit with limited T‐cell responses. [ABSTRACT FROM AUTHOR]

Objective: The diminished expression of microRNA‐146a (miR‐146a) in systemic lupus erythematosus (SLE) contributes to the aberrant activation of the interferon pathway. Despite its significance, the underlying mechanism driving this reduced expression remains elusive. Considering the integral role of enhancers in steering gene expression, our study seeks to pinpoint the SLE‐affected enhancers responsible for modulating miR‐146a expression. Additionally, we aim to elucidate the mechanisms by which these enhancers influence the contribution of miR‐146a to the activation of the interferon pathway. Methods: Circular chromosome conformation capture sequencing and epigenomic profiles were applied to identify candidate enhancers of miR‐146a. CRISPR activation was performed to screen functional enhancers. Differential analysis of chromatin accessibility was used to identify SLE‐dysregulated enhancers, and the mechanism underlying enhancer dysfunction was investigated by analyzing transcription factor binding. The therapeutic value of a lupus‐related enhancer was further evaluated by targeting it in the peripheral blood mononuclear cells (PBMCs) of patients with SLE through a CRISPR activation approach. Results: We identified shared and cell‐specific enhancers of miR‐146a in distinct immune cells. An enhancer 32.5 kb downstream of miR‐146a possesses less accessibility in SLE, and its chromatin openness was negatively correlated with SLE disease activity. Moreover, CCAAT/enhancer binding protein α, a down‐regulated transcription factor in patients with SLE, binds to the 32.5‐kb enhancer and induces the epigenomic change of this locus. Furthermore, CRISPR‐based activation of this enhancer in SLE PBMCs could inhibit the activity of interferon pathway. Conclusion: Our work defines a promising target for SLE intervention. We adopted integrative approaches to define cell‐specific and functional enhancers of the SLE critical gene and investigated the mechanism underlying its dysregulation mediated by a lupus‐related enhancer. [ABSTRACT FROM AUTHOR]

Background: To‐date there have been minimal studies to investigate an association between the gut microbiome and erectile dysfunction. There have been many inflammatory diseases linked to gut microbiome dysbiosis; such as cardiovascular disease and metabolic syndrome. These same inflammatory diseases have been heavily linked to erectile dysfunction. Given the correlations between both conditions and cardiovascular disease and the metabolic syndrome, we believe that it is worthwhile to investigate a link between the two. Objective: To investigate the potential association between the gut microbiome and erectile dysfunction. Methods: Stool samples were collected from 28 participants with erectile dysfunction and 32 age‐matched controls. Metatranscriptome sequencing was used to analyze the samples. Results: No significant differences were found in the gut microbiome characteristics, including Kyoto Encyclopedia of Genes and Genomes richness (p = 0.117), Kyoto Encyclopedia of Genes and Genomes diversity (p = 0.323), species richness (p = 0.364), and species diversity (p = 0.300), between the erectile dysfunction and control groups. Discussion: The association of gut microbiome dysbiosis and pro‐inflammatory conditions has been well studied and further literature continues to add to this evidence. Our main limitation for this study was our small‐sample size due to recruitment issues. We believe that a study with a larger population size may find an association between the gut microbiome and erectile dysfunction. Conclusions: The results of this study do not support a significant association between the gut microbiome and erectile dysfunction. Further research is needed to fully understand the relationship between these two conditions. [ABSTRACT FROM AUTHOR]

Metabolic fingerprints in serum characterize diverse diseases for diagnostics and biomarker discovery. The identification of systemic lupus erythematosus (SLE) by serum metabolic fingerprints (SMFs) will facilitate precision medicine in SLE in an early and designed manner. Here, a discovery cohort of 731 individuals including 357 SLE patients and 374 healthy controls (HCs), and a validation cohort of 184 individuals (SLE/HC, 91/93) are constructed. Each SMF is directly recorded by nano‐assisted laser desorption/ionization mass spectrometry (LDI MS) within 1 minute using 1 µL of native serum, which contains 908 mass to charge features. Sparse learning of SMFs achieves the SLE identification with sensitivity/specificity and area‐under‐the‐curve (AUC) up to 86.0%/92.0% and 0.950 for the discovery cohort. For the independent validation cohort, it exhibits no performance loss by affording the sensitivity/specificity and AUC of 89.0%/100.0% and 0.992. Notably, a metabolic biomarker panel is screened out from the SMFs, demonstrating the unique metabolic pattern of SLE patients different from both HCs and rheumatoid arthritis patients. In conclusion, SMFs characterize SLE by revealing its unique metabolic pattern. Different regulation of small molecule metabolites contributes to the precise diagnosis of autoimmune disease and further exploration of the pathogenic mechanisms. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with abnormal activation of the immune system. Recent attention is increasing about how aberrant lipid and cholesterol metabolism is linked together with type I interferon (IFN‐I) signaling in the regulation of the pathogenesis of SLE. Here, a metabonomic analysis is performed and increased plasma concentrations of oxysterols, especially 7α, 25‐dihydroxycholesterol (7α, 25‐OHC), are identified in SLE patients. The authors find that 7α, 25‐OHC binding to its receptor Epstein–Barr virus‐induced gene 2 (EBI2) in macrophages can suppress STAT activation and the production of IFN‐β, chemokines, and cytokines. Importantly, monocytes/macrophages from SLE patients and mice show significantly reduced EBI2 expression, which can be triggered by IFN‐γ produced in activated T cells. Previous findings suggest that EBI2 enhances immune cell migration. Opposite to this effect, the authors demonstrate that EBI2‐deficient macrophages produce higher levels of chemokines and cytokines, which recruits and activates myeloid cells,T and B lymphocytes to exacerbate tetramethylpentadecane‐induced SLE. Together, via sensing the oxysterol 7α, 25‐OHC, EBI2 in macrophages can modulate innate and adaptive immune responses, which may be used as a potential diagnostic marker and therapeutic target for SLE. [ABSTRACT FROM AUTHOR]

Objective: Disruption of B cell homeostasis and subsequent dominance of effector B cell subsets are critical for the development of systemic lupus erythematosus (SLE). Revealing the key intrinsic regulators involved in the homeostatic control of B cells has important therapeutic value for SLE. This study was undertaken to determine the regulatory role of the transcription factor Pbx1 in B cell homeostasis and lupus pathogenesis. Methods: We constructed mice with B cell–specific deletion of Pbx1. T cell–dependent and T cell–independent humoral responses were induced by intraperitoneal injection of nitrophenyl‐containing hapten (NP) conjugated to keyhole limpet hemocyanin or NP‐Ficoll. The regulatory effects of Pbx1 on autoimmunity were observed in a Bm12‐induced lupus murine model. We investigated mechanisms of Pbx1 using RNA sequencing, the cleavage under targets and tagmentation assay, and chromatin immunoprecipitation–quantitative polymerase chain reaction assay. We transduced B cells from SLE patients with plasmids that overexpressed PBX1 to explore the in vitro therapeutic efficacy of PBX1. Results: Pbx1 was specifically down‐regulated in autoimmune B cells and negatively correlated with disease activity. The deficiency of Pbx1 in B cells resulted in excessive humoral responses following immunization. In the Bm12‐induced lupus model, mice with B cell–specific Pbx1 deficiency displayed enhancements in germinal center responses, plasma cell differentiation, and autoantibody production. Pbx1‐deficient B cells had increased survival and proliferative advantages after activation. Pbx1 regulated genetic programs by directly targeting critical components of the proliferation and apoptosis pathways. In SLE patients, PBX1 expression was negatively correlated with effector B cell expansion; when PBX1 expression was enforced, the survival and proliferative capacity of SLE B cells were attenuated. Conclusion: Our study reveals the regulatory function and mechanism of Pbx1 in adjusting B cell homeostasis and highlights Pbx1 as a therapeutic target in SLE. [ABSTRACT FROM AUTHOR]

Objective: Emerging evidence indicates that a distinct CD11c+T‐bet+ B cell subset, termed age/autoimmune‐associated B cells (ABCs), is the major pathogenic autoantibody producer in lupus. Human lupus is associated with significant metabolic alterations, but how ABCs orchestrate their typical transcription factors and metabolic programs to meet specific functional requirements is unclear. We undertook this study to characterize the metabolism of ABCs and to identify the regulators of their metabolic pathways in an effort to develop new therapies for ABC‐mediated autoimmunity. Methods: We developed a T‐bet–tdTomato reporter mouse strain to trace live T‐bet+ B cells and adoptively transferred CD4+ T cells from bm12 mice to induce lupus. We next sorted CD11c+tdTomato+ B cells and conducted RNA sequencing and an extracellular flux assay. A metabolic restriction to constrain ABC formation was tested in human and mouse B cells. We used a bm12‐induced lupus mouse model to conduct the metabolic intervention. Results: ABCs exhibited a hypermetabolic state with enhanced glycolytic capacity. The increased glycolytic rate in ABCs was promoted by interferon‐γ (IFNγ) signaling. T‐bet, a downstream transcription factor of IFNγ, regulated the gene program of the glycolysis pathway in ABCs by repressing the expression of Bcl6. Functionally, glycolysis restriction could impair ABC formation. The engagement of glycolysis promoted survival and terminal differentiation of antibody‐secreting cells. Administration of a glycolysis inhibitor ameliorated ABC accumulation and autoantibody production in the lupus‐induced bm12 mouse model. Conclusion: T‐bet can couple immune signals and metabolic programming to establish pathogenic ABC formation and functional capacities. Modulation of ABCs favored a metabolic program that could be a novel therapeutic approach for lupus. [ABSTRACT FROM AUTHOR]

Metal halide perovskite have shown great potential for applications in photovoltaics, light‐emitting diodes and photon detectors, mainly owing to their superb optoelectronic properties, low‐cost raw materials and facile fabrication process. Although, polycrystalline perovskite thin‐films have been actively investigated for preparing various optoelectronic devices, the presence of detrimental defects at grain boundaries, serious ion migration and limited stability unfortunately hinder their device performance and practical application. As a contrast, perovskite single crystals (SCs) exhibit no grain boundaries, much lower trap density and much improved stability, hence providing a more attractive choice for not only optoelectronic device applications but also fundamental research. In this review, recent progress in the growth methods of perovskite SCs is summarized, followed by giving a detailed introduction of the intrinsic properties of perovskite SCs including optical properties, defects, charge carrier dynamics, ion migration and stability. On these base, the applications of perovskite SCs in various optoelectronic devices like solar cells, photodetectors, and radiation detectors are discussed, where the relationship between the composition, device architecture and device performance is highlighted. Finally, a tentative discussion on the current challenges and future opportunities in the development of perovskite SCs and optoelectronic devices is presented. [ABSTRACT FROM AUTHOR]

Objective: Increased Toll‐like receptor 7 (TLR‐7) signaling leading to the production of type I interferon (IFN) is an important contributor to human systemic lupus erythematosus (SLE). Protein kinase C and casein kinase substrate in neurons 1 (PACSIN1), a molecule that regulates synaptic vesicle recycling, has been linked to TLR‐7/TLR‐9–mediated type I IFN production in humans and mice, but the underlying mechanism is unknown. We undertook this study to explore the pathogenicity and underlying mechanism of a de novo PACSIN1 missense variant identified in a child with SLE. Methods: PACSIN1 Q59K de novo and null variants were introduced into a human plasmacytoid dendritic cell line and into mice using CRISPR/Cas9 editing. The effects of the variants on TLR‐7/TLR‐9 signaling in human and mouse cells, as well as PACSIN1 messenger RNA and IFN signature in SLE patients, were assessed using real‐time polymerase chain reaction and flow cytometry. Mechanisms were investigated using luciferase reporter assays, RNA interference, coimmunoprecipitation, and immunofluorescence. Results: We established that PACSIN1 forms a trimolecular complex with tumor necrosis factor receptor–associated factor 4 (TRAF4) and TRAF6 that is important for the regulation of type I IFN. The Q59K mutation in PACSIN1 augments binding to neural Wiskott‐Aldrich syndrome protein while it decreases binding to TRAF4, leading to unrestrained TRAF6‐mediated activation of type I IFN. Intriguingly, PACSIN1 Q59K increased TLR‐7 but not TLR‐9 signaling in human cells, leading to elevated expression of IFNβ and IFN‐inducible genes. Untreated SLE patients had high PACSIN1 expression in peripheral blood cells that correlated positively with IFN‐related genes. Introduction of the Pacsin1 Q59K mutation into mice caused increased surface TLR‐7 and TRAIL expression in B cells. Conclusion: PACSIN1 Q59K increases IFNβ activity through the impairment of TRAF4‐mediated inhibition of TLR‐7 signaling, possibly contributing to SLE risk. [ABSTRACT FROM AUTHOR]

Objective: IRF5 plays a crucial role in the development of lupus. Genome‐wide association studies have identified several systemic lupus erythematosus (SLE) risk single‐nucleotide polymorphisms (SNPs) enriched in the IRF5 locus. However, no comprehensive genome editing–based functional analysis exists to establish a direct link between these variants and altered IRF5 expression, particularly for enhancer variants. This study was undertaken to dissect the regulatory function and mechanisms of SLE IRF5 enhancer risk variants and to explore the utilization of clustered regularly interspaced short palindromic repeat interference (CRISPRi) to regulate the expression of disease risk gene to intervene in the disease. Methods: Epigenomic profiles and expression quantitative trait locus analysis were applied to prioritize putative functional variants in the IRF5 locus. CRISPR‐mediated deletion, activation, and interference were performed to investigate the genetic function of rs4728142. Allele‐specific chromatin immunoprecipitation–quantitative polymerase chain reaction and allele‐specific formaldehyde‐assisted isolation of regulatory element–quantitative polymerase chain reaction were used to decipher the mechanism of alleles differentially regulating IRF5 expression. The CRISPRi approach was used to evaluate the intervention effect in monocytes from SLE patients. Results: SLE risk SNP rs4728142 was located in an enhancer region, indicating a disease‐related regulatory function, and risk allele rs4728142‐A was closely associated with increased IRF5 expression. We demonstrated that an rs4728142‐containing region could act as an enhancer to regulate the expression of IRF5. Moreover, rs4728142 affected the binding affinity of zinc finger and BTB domain–containing protein 3 (ZBTB3), a transcription factor involved in regulation. Furthermore, in monocytes from SLE patients, CRISPR‐based interference with the regulation of this enhancer attenuated the production of disease‐associated cytokines. Conclusion: These results demonstrate that the rs4728142‐A allele increases the SLE risk by affecting ZBTB3 binding, chromatin status, and regulating IRF5 expression, establishing a biologic link between genetic variation and lupus pathogenesis. [ABSTRACT FROM AUTHOR]

The practical application of lithium‐sulfur (Li−S) batteries is greatly hindered by the shuttle effect of dissolved polysulfides in the sulfur cathode and the severe dendritic growth in the lithium anode. Adopting one type of effective host with dual‐functions including both inhibiting polysulfide dissolution and regulating Li plating/stripping, is recently an emerging research highlight in Li−S battery. This review focuses on such dual‐functional hosts and systematically summarizes the recent research progress and application scenarios. Firstly, this review briefly describes the stubborn issues in Li−S battery operations and the sophisticated counter measurements over the challenges by dual‐functional behaviors. Then, the latest advances on dual‐functional hosts for both cathode and anode in Li−S full cells are catalogued as species, including metal chalcogenides, metal carbides, metal nitrides, heterostuctures, and the possible mechanisms during the process. Besides, we also outlined the theoretical calculation tools for the dual‐functional host based on the first principles. Finally, several sound perspectives are also rationally proposed for fundamental research and practical development as guidelines. [ABSTRACT FROM AUTHOR]

Objective: Amyopathic dermatomyositis (ADM) is a heterogeneous and life‐threatening autoimmune disease with a high mortality rate. In particular, anti–melanoma differentiation–associated protein 5 antibody–positive patients are at a high risk of developing rapidly progressive interstitial lung disease (RPILD). This study was undertaken to identify immunologic signatures among patients who have ADM with ILD (ADM‐ILD) and to discover the biomarkers predicting prognosis. Methods: The landscape of 42 immune cell phenotypes in the peripheral blood of 82 ADM‐ILD patients and 82 age‐ and sex‐matched healthy donors was assessed by multicolor flow cytometry. Patients were stratified using an unsupervised machine learning method (hierarchical clustering analysis) by immune cell subsets. Multiple Wilcoxon's signed rank tests and supervised machine learning methods were performed to identify important immune cell subsets. Kaplan‐Meier survival analysis with log rank tests was used to create survival curves. Results: We identified 2 distinct clusters correlating with different disease activities and clinical outcomes in ADM‐ILD. Cluster 1 was enriched in the activated CD45RA+HLA–DR+CD8+ T cells with decreased CD56dim natural killer cell proportions and showed a higher prevalence of RPILD and higher mortality. In contrast, the other subgroup, cluster 2 (the nonactivated T cell–dominant cluster), displayed favorable clinical outcomes with high survival rates. Our data also revealed that immunophenotype was an independent risk factor associated with 1‐year survival. Conclusion: Peripheral immunologic features may have the potential to stratify patients with ADM‐ILD according to different disease severity and clinical outcomes, which may have implications for outcome prediction, pathogenesis study, and therapy selection. [ABSTRACT FROM AUTHOR]

Interferon regulatory factor 3 (IRF3)‐induced type I interferon (I‐IFN) production plays key roles in both antiviral and autoimmune responses. IRF3 phosphorylation, dimerization, and nuclear localization are needed for its activation and function, but the precise regulatory mechanisms remain to be explored. Here, we show that the serine/threonine kinase AKT2 interacts with IRF3 and phosphorylates it on Thr207, thereby attenuating IRF3 nuclear translocation in a 14‐3‐3ε‐dependent manner and reducing I‐IFN production. We further find that AKT2 expression is downregulated in viral‐infected macrophages or in monocytes and tissue samples from systemic lupus erythematosus (SLE) patients and mouse models. Akt2‐deficient mice exhibit increased I‐IFN induction and reduced mortality in response to viral infection, but aggravated severity of SLE. Overexpression of AKT2 kinase‐inactive or IRF3‐T207A mutants in zebrafish supports that AKT2 negatively regulates I‐IFN production and antiviral response in a kinase‐dependent manner. This negative role of AKT2 in IRF3‐induced I‐IFN production suggests that AKT2 may be therapeutically targeted to differentially regulate antiviral infection and SLE. Synopsis: Interferon regulatory factor 3 (IRF3)‐induced type I interferon (I‐IFN) production plays key roles during antiviral response and systemic lupus erythematosus (SLE). Here, AKT2 is shown to regulate I‐IFN production by binding to and phosphorylating IRF3 to attenuate IRF3 nuclear translocation, leading to reduced I‐IFN production. AKT2 expression is downregulated in viral‐infected macrophages and in samples from SLE patients and mouse models.I‐IFN stimulation reduces Akt2 transcription and AKT2 inhibits I‐IFN production.AKT2 binds and phosphorylates IRF3 at Thr207 to reduce IRF3 nuclear localization.Akt2 deficiency promotes IFNβ1 production to favor antiviral response while enhancing SLE in mouse models. [ABSTRACT FROM AUTHOR]

Summary: Background: Hepatitis B surface antigen (HBsAg) seroclearance is the most important milestone indicating favourable clinical outcomes in patients with chronic hepatitis B (CHB). However, it is difficult to achieve due to the impaired HBV‐specific immunity, such as programmed cell death 1 (PD‐1)‐associated T cell exhaustion. We assessed soluble PD‐1 (sPD‐1) as a novel seromarker for predicting spontaneous HBsAg loss. Methods: Serial serum levels of sPD‐1 were evaluated in 1046 untreated hepatitis B e antigen (HBeAg)‐seronegative individuals who had achieved undetectable serum HBV DNA. Multiple regression analyses were applied to assess associations among baseline and subsequent sPD‐1 levels, HBsAg decline during follow‐up, and spontaneous HBsAg seroclearance. Results: A total of 390 individuals achieved spontaneous HBsAg seroclearance during 6464.4 person‐years of follow‐up. Baseline sPD‐1 levels were inversely associated with baseline HBsAg levels (qHBsAg) as well as a greater decline in qHBsAg during follow‐up. Incidence rates of HBsAg seroclearance were 11.5, 61.7, 96.7 and 151.0 per 1000 person‐years for sPD‐1 levels of ≥4000, 536‐3999, 125‐535 and <125 pg/mL, respectively (Ptrend < 0.0001). Compared with baseline sPD‐1 levels ≥4000 pg/mL, the rate ratio (95% CI) of HBsAg seroclearance was 2.1 (1.1‐3.9), 3.0 (1.6‐5.5) and 5.1 (2.8‐9.5), for baseline sPD‐1 levels of 536‐3999, 125‐535 and <125 pg/mL, respectively, after adjustment for sex, age and serum alanine aminotransferase and HBsAg levels. Conclusion: sPD‐1 level is a novel marker which independently predicts spontaneous HBsAg seroclearance of HBeAg‐negative inactive CHB patients with undetectable HBV DNA. (word count: 234, <250). [ABSTRACT FROM AUTHOR]

Stress/strain engineering is believed to be an effective way to adjust the thermal conductivity of materials dynamically or as needed. Compared with bulk materials, micro‐/nanoscale structures can withstand greater stress/deformations that lead to evident changes in their thermal conductivity after undergoing stress/strain; this phenomenon has been predicted by theoretical simulations. Nevertheless, measuring the effective thermal conductivity of a single wire of a small size upon controllable bending angles has faced major challenges. Herein, a method using VO2 tag as a temperature indicator is developed to achieve the in situ quantitative measurement of the thermal conductivity of bent silicon microwires (MWs), where thermally insulated spider silk is used to adjust the position of the suspended end of wires for different bending angles. It is found that the thermal conductivity of Si wires increases and then decreases upon subsequent bending; it indicates that the thermal conductivity of MWs can be dynamically tuned by bending. Further studies reveal that the variation of thermal conductivity is reversible with small bending (elastic) and irreversible with large bending (plastic). With this setup, new thermophysical properties of materials are explored at small scales, and possible stress/strain‐gated thermal switches emerge. [ABSTRACT FROM AUTHOR]

Objective: The benefit of Se supplementation in rheumatoid arthritis (RA) has been tested in clinical trials, but results remain inconclusive. The objective of this study was to specifically investigate the potential benefit of supranutritional Se by examining human samples from an area with supranutritional Se intake and testing a mouse model of RA. Methods: Peripheral blood mononuclear cells (PBMCs) from RA patients (N = 57) and healthy controls (HC, N = 71) from an area of supranutritional Se intake (Enshi, Hubei, China) were analysed by flow cytometry. Serum cytokine and Se levels were measured by cytometric beads array (CBA) and inductively coupled plasma mass spectrometry (ICP‐MS), respectively. With sufficient or supranutritional selenium intake, mice were induced with collagen‐induced arthritis (CIA) and examined for disease activity and immunopathology. The influence of Se supplementation in the generation of RANKL‐expressing osteoclastogenic CD4+ T cells was investigated by in vitro assays. Results: In Enshi city, HC showed the above‐normal concentrations of serum Se concentrations while RA patients were enriched in the normal range (70–150 ng mL−1) or below. RA patients with higher Se levels demonstrated milder disease and lower levels of C‐reactive protein, IL‐6, RANKL and Th17 cells. In the mouse CIA model, supranutritional Se supplementation delayed disease onset, ameliorated joint pathology and reduced CD4+CD44+RANKL+ T cells. Se supplementation could suppress RANKL expression in cultured mouse Th17 cells. Conclusion: Supranutritional Se suppresses RANKL‐expressing osteoclastogenic CD4+ T cells and could be beneficial to RA, which warrants formal testing in randomised clinical trials. [ABSTRACT FROM AUTHOR]

Introduction: Toxoplasmosis is a life‐threatening complication after hematopoietic stem cell transplantation (HSCT). However, for several reasons, clinicians know little about Toxoplasma infection. Case presentation: We report a case of toxoplasmosis that was diagnosed by bone marrow smear and metagenomic next‐generation sequencing (mNGS) after HSCT in a boy. Additionally, we summarize the characteristics of toxoplasmosis after pediatric HSCT reported in the literature published in PubMed. Conclusion: Clinicians should increase their awareness of toxoplasmosis in children after HSCT and implement pre‐transplant screening and post‐transplant monitoring and prevention in future according to the national conditions of our country. [ABSTRACT FROM AUTHOR]

Objectives: Low‐dose interleukin‐2 (IL‐2) has shown promising clinical benefits in the treatment of systemic lupus erythematosus (SLE), but how this therapy alleviates pathogenic humoral immunity remains not well understood. The dilemma is that IL‐2 can suppress both follicular helper and regulatory T (Tfh and Tfr) cells, which counteract each other in regulating autoantibody production. Methods: Female NZB/W F1 mice received recombinant human IL‐2 (3 × 104 IU/dose) in three treatment regimens: (1) short, daily for 7 days; (2) medium, daily for 14 days, and (3) long, every second day for 28 days. Tfh (Foxp3−CXCR5+Bcl6+), Tfr (Foxp3+CXCR5+Bcl6+), germinal centre (GC, B220+GL‐7+Fas+) and antibody‐secreting cell (ASC, B220−CD138+TACI+) were analysed by flow cytometry. Serum anti‐dsDNA level was determined by ELISA. Kidney pathology was evaluated by H&E and immunofluorescence staining. Circulating Tfh and Tfr cells in SLE patients treated with low‐dose IL‐2 from a previous clinical trial (NCT02084238) was analysed. Results: Low‐dose IL‐2 treatment consistently increased Tfr/Tfh ratio in mice and SLE patients, because of a stronger suppression on Tfh cells than Tfr cells. Three treatment regimens revealed distinct immunological features. Tfh suppression was observed in all regimens, but Tfr suppression and GC reduction were recorded in just medium and long regimens. Only the long treatment regimen resulted in inhibited ASC differentiation in spleen, which was accompanied by reduced anti‐dsDNA titres and ameliorated kidney pathology. Conclusion: Low‐dose IL‐2 therapy increases the Tfr/Tfh ratio, and a less frequent and prolonged treatment can alleviate pathogenic humoral immunity and improve renal function. [ABSTRACT FROM AUTHOR]

Objective: Type I interferons (IFNs) are critical in the development of systemic lupus erythematosus (SLE). Metabolic abnormalities cause dysregulation of multiple immune cells, but the metabolic regulation of type I IFN production is not well clarified in SLE. We undertook this study to define amino acid metabolism features in SLE and to explore the function of disease‐relevant metabolites in the control of plasmacytoid dendritic cell (pDC)–mediated type I IFN production and the progression of SLE. Methods: Metabolomic profiling of the serum from SLE patients and healthy controls was performed by mass spectrometry. The effects of SLE‐related metabolites on type I IFN production were explored in human and mouse pDCs. The reactive oxygen species (ROS) levels of pDCs from wild‐type and Ncf1−/− mice were measured by flow cytometry. Mechanisms were investigated by RNA sequencing and immunoblotting. In vivo effects of SLE‐relevant metabolites were systemically analyzed in B6.Cg‐Sle1NZM2410/Aeg Yaa/DcrJ mice. Results: Taurine was higher in the serum from SLE patients compared to healthy controls (P < 0.001) and rheumatoid arthritis patients (P < 0.001). Taurine content was positively correlated with disease activity and the expression of IFN signature genes. The addition of taurine facilitated IFN regulatory factor 7 phosphorylation and enhanced type I IFN production by reducing the ROS levels in pDCs in a neutrophil cytosolic factor 1–dependent manner. Taurine supplementation promoted expression of type I IFN–induced genes, activated lymphocytes, and increased autoantibodies and proteinuria, leading to more serious nephritis. Conclusion: Taurine metabolism is involved in the development of SLE by enhancing pDC‐mediated type I IFN production. Targeted inhibition of taurine or implementation of a taurine‐restricted diet has therapeutic potential in SLE. [ABSTRACT FROM AUTHOR]

The emerging soft robots have attracted increasing interests and gotten rapidly developed, but it is still challenging to substantially promote their response speed and work density. In addition, the wireless way to conveniently trigger the devices, especially for the centimeter‐scale ones, is highly desired. Herein, the multistimuli‐responsive insect‐scale soft robotics is reported based on a super‐aligned VO2 nanowire arrays (NAs)/carbon nanotube (CNT) bimorph film, comprehensively addressing aforementioned problems. The as‐prepared VO2 NA/CNT bimorph shows improved actuation performance, anisotropic behavior, rapid response to various stimuli (heat, light, and electricity), and multiple movement modes (bending and torsion). Consequently, diverse untethered, insect‐scale soft robots, serving as biomimetic crawler, lifter, gripper, wing of flying robots, torsional robot, and so on are successfully demonstrated. The findings provide an effective strategy to develop high‐performance macroscopic mechanical devices by assembling functional nanostructures. [ABSTRACT FROM AUTHOR]

Soil detachment by rill flow is a key process of rill erosion, modelling this process can help in understanding rill erosion mechanisms. However, many soil detachment models are established on conceptual assumptions rather than experimental data. The objectives of this study were to establish a model of soil detachment by rill flow based on flume experimental data and to quantitatively verify the model. We simulated the process of soil detachment by rill flow in flume experiments with a soil‐feeding hopper using loessial soil on steep slopes. Seven flow discharges, six slopes and five sediment loads were combined. Soil detachment capacity, sediment transport capacity, and soil detachment rate by rill flow under different sediment loads were measured. The process of soil detachment by rill flow can be modelled by a dual power function based on soil detachment capacity and transport capacity deficit as variables. The established model exhibited high credibility (NSE=0.97; R2=0.97). The contributions of soil detachment capacity and transport capacity deficit to soil detachment rate by rill flow reached 60% and 36%, respectively. Soil detachment capacity exerted more influence on soil detachment rate than did transport capacity deficit. The performance of the WEPP rill erosion equation is also favourable (NSE=0.95; R2=0.97). The two power exponents in the model we established strengthen the role of soil detachment capacity in soil detachment rate and weaken that for transport capacity deficit. Soil detachment capacity and transport capacity deficit played important roles in the determination of soil detachment rate by rill flow. The results can be applied to implement the numerical modeling and prediction of rill erosion processes on steep loessial hillslopes. © 2019 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Ruddlesden–Popper perovskite (RPP) materials have attracted great attention due to their superior stability, where the organic spacer dominantly determines the stability and efficiency of RPP solar cells, but research still lacks the systematical understanding of the interplay of binary spacer in the overall mixture range of 0–100% in RPPs on the precursor chemistry, film quality, and carrier behavior. Herein, a series of novel binary spacer RPP films of (PBA1−xBAx)2MA3Pb4I13 (BA = n‐butylammonium, PBA = 4‐phenylbutan‐1‐aminium, and MA = methylammonium) is successfully fabricated to reveal the interplay of binary spacers. The incorporation of 50% BA into the (PBA)2MA3Pb4I13 precursor solution increases the colloidal size and reduces nucleation sites, and therefore forms a very smooth film with much larger crystal grains and a higher degree of crystal preferential orientation, resulting in a significant reduction of trap states. The resulting combination of fast electron transfer and efficient electron extraction facilitates to effectively suppress the trap‐assisted charge recombination and remarkably decrease charge recombination losses. Consequently, the (PBA0.5BA0.5)2MA3Pb4I13 device achieves a champion efficiency of 16.0%, among the highest reported efficiencies for RPP devices. Furthermore, this device demonstrates good ambient, illumination, and thermal stabilities, retaining 60–93% of its initial efficiency after 30 days of various ageing. [ABSTRACT FROM AUTHOR]

The performance of 1D nano/microbeam‐based devices greatly relies on heat dissipation to substrates. The surface roughness plays a key role in interfacial heat transport while this issue is seldom investigated due to the difficulty in quantitative determination of thermal contact resistance (TCR) at nanoscale. Here, the impact of interfacial roughness on heat transport at solid–solid interface by taking VO2 microbeam on Si substrate (VO2/Si) as a prototype is investigated. With the increased interface roughness from atomic fluctuation to ≈100 nm, it is found that an unusual uncertainty emerges in thermal interface transport along with the dramatical increase in TCR with two orders of magnitudes. Besides, a single‐layer graphene is inserted into VO2/Si interface as thermal interface material to study its performance under interface roughness. The inserted graphene not only substantially reduces the TCR but also reduces the uncertainty of thermal interface transport. This enhancement is even remarkable at rougher interface. Microscopic characterization and molecular dynamics simulation suggest that suspended condition and high heat conductivity of graphene on rough surface are responsible for the above effects. This work provides the quantitative evaluation of TCR and contributes to the in‐depth understanding on heat transport at imperfect interface. [ABSTRACT FROM AUTHOR]

A series of static and sliding indentation (ie, scratching) was performed and characterized on a wide range of optical workpiece materials [single crystals of Al2O3 (sapphire), SiC, Y3Al5O12 (YAG), CaF2, and LiB3O5 (LBO); a SiO2–Al2O3–P2O5–Li2O glass ceramic (Zerodur); and glasses of SiO2:TiO2 (ULE), SiO2 (fused silica), and P2O5–Al2O3–K2O–BaO (Phosphate)] at various applied loads using various indenters (Vickers, 10 µm conical, and 200 µm conical). Despite having different load dependencies, the lateral crack depth formed during sliding indentation quantitatively scales with that formed during static indentation, explaining why static indentation has been historically effective in describing various grinding parameters. Depending on the indenter geometry, the amount of residual trench damage (plastic deformation and local fracturing) during sliding indentation was often enhanced by more than an order of magnitude compared with static indentation. A simple ploughing scratch model, which considers both tangential and normal stresses (where the tangential stress is amplified by relatively small tangential contact area), explains this enhancement and other observed trends. Accounting for the high correlation between residual trench depth and volumetric fracturing, the model is extended to estimate the amount of fracture damage as a function of the material properties of the workpiece, indenter geometry, and applied load. Such a model has utility in the design of optimized grinding processes, particularly the abrasive geometry. Finally, at higher loads (>1 N), lateral cracks were often observed to preferentially propagate in the forward scratching direction, as opposed to perpendicular to the scratch as typically observed. High‐speed imaging of the scratch process confirms that these cracks propagate ahead of the sliding indenter during the scratching event. Finite element stress analysis suggests the ploughing frictional forces increase the mode I tensile stresses at the leading edge of the sliding indenter explaining the direction of crack propagation of such cracks. [ABSTRACT FROM AUTHOR]

Metabolic fingerprints of biofluids encode diverse diseases and particularly urine detection offers complete non‐invasiveness for diagnostics of the future. Present urine detection affords unsatisfactory performance and requires advanced materials to extract molecular information, due to the limited biomarkers and high sample complexity. Herein, we report plasmonic polymer@Ag for laser desorption/ionization mass spectrometry (LDI‐MS) and sparse‐learning‐based metabolic diagnosis of kidney diseases. Using only 1 μL of urine without enrichment or purification, polymer@Ag afforded urine metabolic fingerprints (UMFs) by LDI‐MS in seconds. Analysis by sparse learning discriminated lupus nephritis from various other non‐lupus nephropathies and controls. We combined UMFs with urine protein levels (UPLs) and constructed a new diagnostic model to characterize subtypes of kidney diseases. Our work guides urine‐based diagnosis and leads to new personalized analytical tools for other diseases. [ABSTRACT FROM AUTHOR]

Sodium molybdate (Na−Mo−O) wrapped by graphene oxide (GO) composites have been prepared via a simple in‐situ precipitation method at room temperature. The composites are mainly constructed with one dimension (1D) ultra‐long sodium molybdate nanorods, which are wrapped by the flexible GO. The introduction of GO is expected to not merely provide more active sites for lithium‐ions storage, but also improve the charge transfer rate of the electrode. The testing electrochemical performances corroborated the standpoint: The Na−Mo−O/GO composites delivers specific capacities of 718 mAh g−1 after 100 cycles at 100 mA g−1, and 570 mAh g−1 after 500 cycles at a high rate of 500 mA g−1; for comparison, the bare Na−Mo−O nanorod shows a severe capacity decay, which deliver only 332 mAh g−1 after 100 cycles at 100 mA g−1. In view of the cost‐efficient and less time‐consuming in synthesis, and one‐step preparation without further treatment, these Na−Mo−O nanorods/GO composites present potential and prospective anodes for LIBs. [ABSTRACT FROM AUTHOR]

The nanomechanical deformations on a broad range of optical material surfaces (single crystals of Al2O3 [sapphire], SiC, Y3Al5O12 [YAG], CaF2, and LiB3O5 [LBO]; a SiO2–Al2O3–P2O5–Li2O glass‐ceramics [Zerodur]; and glasses of SiO2:TiO2 [ULE], SiO2 [fused silica], and P2O5–Al2O3–K2O–BaO [Phosphate]) near the elastic‐plastic load boundary have been measured by nanoindentation and nanoscratching to mimic the nanoplastic removal caused by a single slurry particle during polishing. Nanoindenation in air was performed to determine the workpiece hardness at various loads using a commercial nanoindenter with a Berkovich tip. Similarly, an atomic force microscope (AFM) with a stiff diamond coated tip (150 nm radius) was used to produce nanoplastic scratches in air and aqueous environments over a range of applied loads (~20‐170 μN). The resulting nanoplastic deformation of the nanoscratches were used to calculate the removal function (i.e., depth per pass) which ranged from 0.18 to 3.6 nm per pass for these materials. A linear correlation between the nanoplastic removal function and the polishing rate (using a fixed polishing process with colloidal silica slurry on a polyurethane pad) of these materials was observed implying that: (a) the polishing mechanism using colloidal silica slurry can be dominated by mechanical rather than chemical interactions; and (b) the nanoplastic removal function, as opposed to interface particle interactions, is the controlling factor for the polishing material removal rate. Furthermore, this correlation is consistent with the Ensemble Hertzian Multi‐Gap (EHMG) microscopic material removal rate model described previously. The nanoplastic removal depth was also found to correlate to the measured nanoindentation hardness (H1) of the optical material, scaling as H1−3.5. Two‐dimensional (2D) finite element analysis simulations of nanoindentation showed a similar nonlinear dependence of plastic deformation with the workpiece material hardness. The findings of this study are used to determine an effective Preston coefficient for the material removal rate expression and enhance the predictive nature of the nanoplastic polishing rate for various materials utilizing their material properties. [ABSTRACT FROM AUTHOR]

A partial charge‐based chemical polishing model has been developed, which can serve as metric for describing the relative polishing material removal rate for different combinations of slurries and workpieces. A series of controlled polishing experiments utilizing a variety of colloidal polishing slurries (SiO2, CeO2, ZrO2, MgO, Sb2O5) and optical materials [single crystals of Al2O3 (sapphire), SiC, Y3Al5O12 (YAG), CaF2, and LiB3O5 (LBO); a SiO2‐Al2O3‐P2O5‐Li2O glass ceramic (Zerodur); and glasses of SiO2:TiO2 (ULE), SiO2 (fused silica), and P2O5‐Al2O3‐K2O‐BaO (Phosphate)] was performed and its material removal rate was measured. As previously proposed by Cook (J Non‐Cryst Solids. 1990;120:152), for many polishing systems, the removal rate is governed by a series of chemical reactions which include the formation of a surface hydroxide, followed by condensation of that hydroxyl moiety with the polishing particle, and a subsequent hydrolysis reaction. The rate of condensation can often be the rate limiting step, thus it can determine the polishing material removal rate. By largely keeping the numerous other factors that influence material removal rate fixed (such as due to particle size distributions, interface interactions, pad topography, kinematics, and applied pressure), the material removal rate is shown to scale exponentially with the partial charge difference (δwp‐s) between the workpiece and polishing slurry particle for many of the slurry‐workpiece combinations indicating that condensation rate is the rate limiting step. The partial charge (δ) describes the equilibrium distribution of electron density between chemically bonded atoms and is related to the electronegativity of the atoms chemically bonded to one another. This partial charge model also explains the age‐old experimental finding of why cerium oxide is the most effective polishing slurry for chemical removal of many workpieces. Some of the slurry‐workpiece combinations that did not follow the partial charge dependence offer insight to other removal mechanisms or rate limiting reaction pathways. [ABSTRACT FROM AUTHOR]

Three new mixed‐ligand coordination polymers of CuII, namely, [Cu(Fbtx)(L1)(H2O)]n (1), [Cu(Fbtx)0.5(HL2)(H2O)2]n (2), and {[Cu(Fbtx)1.5(HL3)(H2O)]·H2O}n (3) [Fbtx = 2,3,5,6‐tetrafluoro‐1,4‐bis(1,2,4‐triazole‐1‐ylmethyl)benenze, H2L1 = terephthalic acid, H3L2 = trimesic acid, NaH2L3 = 5‐sulfoisophthalic acid monosodium salt], were hydrothermally synthesized and structurally characterized by elemental analysis, IR spectra, and single‐crystal and powder X‐ray diffraction techniques. All the complexes have a two‐dimensional (2D) coordination layer structure. Of these, 1 displays a planar 44‐sql structure whereas both 2 and 3 are highly undulated 63‐hcb nets. Moreover, their thermal stability and catalytic behaviors in the aerobic oxidation of 4‐methoxybenzyl alcohol were also investigated as well. The results indicate that the benzene dicarboxylate ligands have an effective influence on the structures and catalytic properties of the resulting coordination polymers. [ABSTRACT FROM AUTHOR]

Objective: Increasing evidence indicates that the cyclic GMP‐AMP synthase/stimulator of interferon genes (cGAS/STING) signaling pathway has a critical pathogenic role in systemic lupus erythematosus (SLE). Expression levels of the interferon (IFN)–inducible gene IFIT3 are elevated in SLE patients. However, it is still not clear how IFIT3 contributes to the pathogenesis of SLE. This study was undertaken to investigate the activation of the cGAS/STING signaling pathway in human SLE monocytes, and to determine how elevated expression of IFIT3 could contribute to overactive cGAS/STING signaling in patients with SLE. Methods: Monocytes from SLE patients or healthy controls were examined for activity of the cGAS/STING signaling pathway and expression levels of IFIT3. Correlations between cGAS/STING signaling activity and SLE clinical features were analyzed. Gain‐ or loss‐of‐function experiments were used to determine the role of IFIT3 in cGAS/STING signaling. Coimmunoprecipitation assays were used to identify the interaction between IFIT3 and other proteins. Results: The cGAS/STING signaling pathway was found to have enhanced activity in monocytes from SLE patients compared to healthy controls, as indicated by the higher expression of IFNβ downstream. Levels of IFIT3 were significantly elevated in human SLE monocytes, and this was positively correlated with the activity of the cGAS/STING signaling pathway. In vitro, the expression of VACV70‐induced IFNβ was reduced by knockdown of IFIT3, whereas overexpression of IFIT3 produced an opposite effect. Finally, IFIT3 was found to interact with both STING and TANK‐binding kinase 1. Conclusion: These findings suggest that IFIT3 is one of the genes that contributes to the overactive cGAS/STING signaling pathway in human SLE monocytes. IFIT3 may therefore serve as a novel therapeutic target for blocking the production of type I IFN and other proinflammatory cytokines by the cGAS/STING signaling pathway in patients with SLE. [ABSTRACT FROM AUTHOR]

Electrostatic discharge (ESD) is a significant cause of yield loss in FPD (Flat Panel Display) array manufacturing. LTPS‐TFT Arrays processing includes a series of chucking and conveyance steps, in which, some of these steps would generate triboelectric charge [1, 2]. Although low‐impedance materials for equipment contact parts with glass substrate have been adopted, and good grounding has been implemented, ESD still happens frequently. In order to understand the root‐cause of ESD and to minimize the ESD effect, it is necessary to have a systematic research on LTPS‐TFT Arrays processing. By studying and identifying the locations of ESD in different LTPS‐AMOLED products , we found three ESD causes related to the different array designs as described below: Overlap between adjacent metal layers is easy to generate ESD, e.g. the overlap of metal 1 line of EM and metal 2 jumper line of Vdata, the overlap of metal 1 jumper line of Vdata and metal 2 jumper line of VDD, the overlap of metal 2 line of Vref and metal 1 jumper line of Vdata.Research on ESD in products' GIP (Gate Driver in Panel) area indicates that the distance of Capacity C1/C2 in GIP‐Scan circuit, D1 for short, and the area difference of C1/C2 have an obvious correlation with ESD, in which the products' resistance to ESD risk is enhanced with the increase of D1 distance and the decrease of C1/C1 area difference.Study of ESD in CT (Cell Test) area shows that CT ESD has a strong correlation with IC Pad, including COF Pad & IC output Pad, in which, ESD occurs easily when IC Pad is connected to CT circuit directly. By optimizing array design, products with excellent resistance to ESD risks can be obtained. [ABSTRACT FROM AUTHOR]

Objective: Reactive arthritis (ReA) is an inflammatory disorder occurring several weeks after gastrointestinal or genitourinary tract infections. HLA–B27 positivity is considered a risk factor, although it is not necessarily predictive of disease incidence. Among nongenetic factors, the intestinal microbiome may play a role in disease susceptibility. The objective of this study was to characterize the gut microbiota and host gene interactions in ReA and postinfectious spondyloarthritis. Methods: Adult subjects with peripheral spondyloarthritis and control subjects with preceding infections who did not develop arthritis were prospectively recruited from a geographic region with a high prevalence of ReA. Clinical variables, HLA status, and 16S ribosomal RNA gene sequencing of intestinal microbiota were analyzed. Results: Subjects with ReA showed no significant differences from controls in gut bacterial richness or diversity. However, there was a significantly higher abundance of Erwinia and Pseudomonas and an increased prevalence of typical enteropathogens associated with ReA. Subjects with ultrasound evidence of enthesitis were enriched in Campylobacter, while subjects with uveitis and radiographic sacroiliitis were enriched in Erwinia and unclassified Ruminococcaceae, respectively; both were enriched in Dialister. Host genetics, particularly HLA–A24, were associated with differences in gut microbiota diversity irrespective of disease status. We identified several co‐occurring taxa that were also predictive of HLA–A24 status. Conclusion: This is the first culture‐independent study characterizing the gut microbial community in postinfectious arthritis. Although bacterial factors correlated with disease presence and clinical features of ReA, host genetics also appeared to be a major independent driver of intestinal community composition. Understanding of these gut microbiota–host genetic relationships may further clarify the pathogenesis of postinfectious spondyloarthritides. [ABSTRACT FROM AUTHOR]

During optical glass polishing, a number of interactions between the workpiece (i.e., glass), polishing slurry, and pad can influence the resulting workpiece roughness at different spatial scale lengths. In our previous studies, the particle size distribution of the slurry, the pad topography, and the amount of material removed by a single particle on the workpiece were shown to strongly correlate with roughness at AFM scale lengths (nm-μm) and weakly at μ-roughness scale lengths (μm-mm). In this study, the polishing slurry pH and the generation of glass removal products are shown to influence the slurry particle spatial and height distribution at the polishing interface and the resulting μ-roughness of the glass workpiece. A series of fused silica and phosphate glass samples were polished with various ceria and colloidal silica slurries over a range of slurry pH, and the resulting AFM roughness and μ-roughness were measured. The AFM roughness was largely invariant with pH, suggesting that the removal function of a single particle is unchanged with pH. However, the μ-roughness changed significantly, increasing linearly with pH for phosphate glass and having a maximum at an intermediate pH for fused silica. In addition, the spatial and height distribution of slurry particles on the pad (as measured by laser confocal microscopy) was determined to be distinctly different at low and high pH during phosphate glass polishing. Also, the zeta potential as a function of pH was measured for the workpiece, slurry, and pad with and without surrogate glass products (K3 PO4 for phosphate glass and Si( OH)4 for silica) to assess the role of interfacial charge during polishing. The addition of K3 PO4 significantly raised the zeta potential, whereas addition of Si( OH)4 had little effect on the zeta potential. An electrostatic DLVO three-body force model, using the measured zeta potentials, was used to calculate the particle-particle, particle-workpiece, and particle-pad attractive and repulsive forces as a function of pH and the incorporation of glass products at the interface. The model predicted an increase in particle-pad attraction with an increase in pH and phosphate glass products consistent with the measured slurry distribution on the pads during phosphate glass polishing. Finally, a slurry 'island' distribution gap ( IDG) model has been formulated which utilizes the measured interface slurry distributions and a load balance to determine the interface gap, the contact area fraction, and the load on each slurry 'island'. The IDG model was then used to simulate the workpiece surface topography and μ-roughness; the results show an increase in roughness with pH similar to that observed experimentally. [ABSTRACT FROM AUTHOR]

Objective Systemic juvenile idiopathic arthritis (JIA) is an inflammatory disease of childhood in which cells of the monomyelocytoid lineage are thought to be key effector cells. Monocytes from patients with systemic JIA have a distinct phenotype, with features of both M1 and M2 alternative activation. MicroRNAs are critical regulators of monocyte polarization and function, but cellular microRNAs in systemic JIA have not been examined systematically. Methods MicroRNA TaqMan arrays were used to determine the expression profiles of monocytes from children with systemic JIA. Expression of microRNA-125a-5p (miR-125a-5p) and its contribution to monocyte polarization were examined using in vitro-polarized THP-1 cells and primary human monocytes. Results A total of 110 microRNAs were found to be differentially expressed in monocytes from patients with active systemic JIA, including molecules implicated in rheumatoid arthritis pathogenesis, cytokine production, and monocyte polarization. MicroRNA-125a-5p was identified as being highly up-regulated in monocytes from children with active systemic JIA, as compared to those from children with clinically inactive JIA or those with active polyarticular JIA, and correlated with systemic features of the disease. In vitro, monocyte miR125a-5p expression was increased after polarization under M2b or M2c conditions. Inhibition of miR-125a-5p showed that this microRNA contributed to full polarization of M2b regulatory macrophages. In contrast, miR-125a-5p overexpression enhanced M2b polarization and altered other polarized populations, including increasing the production of M2 markers. Indeed, in vitro overexpression of this microRNA altered the macrophage phenotype toward that observed in systemic JIA. Conclusion Children with active systemic JIA have profound alterations in the expression of microRNAs that are implicated in monocyte function and polarization. One of these microRNAs, miR-125a-5p, is also a regulator of immunoregulatory M2b macrophages. [ABSTRACT FROM AUTHOR]

Objective Type I interferon (IFN) is a critical pathogenic factor during the progression of lupus nephritis (LN). Although microRNAs (miRNAs) have been shown to control the IFN response in immune cells in LN, the role of miRNAs in resident renal cells remains unclear. We undertook this study to investigate the role of microRNA-130b (miR-130b) in the IFN pathway in renal cells as well as its therapeutic effect in LN. Methods Kidney tissues from patients and (NZB × NZW)F1 lupus-prone mice were collected for detecting miR-130b levels. Primary renal mesangial cells (RMCs) were used to determine the role of miR-130b in the IFN pathway. We overexpressed miR-130b by administering miR-130b agomir in a mouse model of IFNα-accelerated LN to test its therapeutic efficacy. Results Down-regulated miR-130b expression was observed in kidney tissues from patients and lupus-prone mice. Further analysis showed that underexpression of miR-130b correlated negatively with abnormal activation of the IFN response in LN patients. In vitro, overexpressing miR-130b suppressed signaling downstream from the type I IFN pathway in RMCs by targeting IFN regulatory factor 1 (IRF-1). The opposite effect was observed when endogenous miR-130b expression was inhibited. The inverse correlation between IRF1 and miR-130b levels was detected in renal biopsy samples from LN patients. More importantly, in vivo administration of miR-130b agomir reduced IFNα-accelerated progression of LN, with decreased proteinuria, lower levels of immune complex deposition, and lack of glomerular lesions. Conclusion MicroRNA-130b is a novel negative regulator of the type I IFN pathway in renal cells. Overexpression of miR-130b in vivo ameliorates IFNα-accelerated LN, providing potential novel strategies for therapeutic intervention in LN. [ABSTRACT FROM AUTHOR]

Glass optics with ultra-low roughness surfaces (<2 Å rms) are strongly desired for high-end optical applications (e.g., lasers, spectroscopy, etc.). The complex microscopic interactions that occur between slurry particles and the glass workpiece during optical polishing ultimately determine the removal rate and resulting surface roughness of the workpiece. In this study, a comprehensive set of 100 mm diameter glass samples (fused silica, phosphate, and borosilicate) were polished using various slurry particle size distributions ( PSD), slurry concentrations, and pad treatments. The removal rate and surface roughness of the glasses were characterized using white light interferometry and atomic force microscopy. The material removal mechanism for a given slurry particle is proposed to occur via nano-plastic deformation (plastic removal) or via chemical reaction (molecular removal) depending on the slurry particle load on the glass surface. Using an expanded Hertzian contact model, called the Ensemble Hertzian Multi-gap ( EHMG) model, a platform has been developed to understand the microscopic interface interactions and to predict trends of the removal rate and surface roughness for a variety of polishing parameters. The EHMG model is based on multiple Hertzian contacts of slurry particles at the workpiece-pad interface in which the pad deflection and the effective interface gap at each pad asperity height are determined. Using this, the interface contact area and each particle's penetration, load, and contact zone are determined which are used to calculate the material removal rate and simulate the surface roughness. Each of the key polishing variables investigated is shown to affect the material removal rate, whose changes are dominated by very different microscopic interactions. Slurry PSD impacts the load per particle distribution and the fraction of particles removing material by plastic removal. The slurry concentration impacts the areal number density of particles and fraction of load on particles versus pad. The pad topography impacts the fraction of pad area making contact with the workpiece. The glass composition predominantly impacts the depth of plastic removal. Also, the results show that the dominant factor controlling surface roughness is the slurry PSD followed by the glass material's removal function and the pad topography. The model compares well with the experimental data over a variety of polishing conditions for both removal rate and roughness and can be extended to provide insights and strategies to develop practical, economic processes for obtaining ultra-low roughness surfaces while simultaneously maintaining high material removal rates. [ABSTRACT FROM AUTHOR]

Presented are the ionothermal syntheses, characterizations, and properties of a series of two- and three-dimensional selenidostannate compounds synergistically directed by metal-amine complex (MAC) cations and ionic liquids (ILs) of [Bmmim]Cl (Bmmim=1-butyl-2,3-dimethylimidazolium). Four selenidostannates, namely, 2D-(Bmmim)3[Ni(en)3]2[Sn9Se21]Cl ( 1, en=ethylenediamine), 2D-(Bmmim)8[Ni2(teta)2(μ-teta)]Sn18Se42 ( 2, teta=triethylenetetramine), 2D-(Bmmim)4[Ni(tepa)Cl]2[Ni(tepa)Sn12Se28] ( 3, tepa=tetraethylenepentamine), and 3D-(Bmmim)2[Ni(1,2-pda)3]Sn8Se18 ( 4, 1,2-pda=1,2-diaminopropane), were obtained. Single-crystal X-ray diffraction analyses revealed that compounds 1 and 2 possess a lamellar anionic [Sn3Se7] n2 n− structure comprising distinct eight-membered ring units, whereas 3 features a MAC-decorated anionic [Ni(tepa)Sn12Se28] n6 n− layered structure. In contrast to 1- 3, compound 4 exhibits a 3D open framework of anionic [Sn4Se9] n2 n−. The structural variation from 1 to 4 clearly indicates that on the basis of the synergistic structure-directing ability of the MACs and ILs, variation of the organic polyamine ligand has a significant impact on the formation of selenidostannates. [ABSTRACT FROM AUTHOR]

The nanomechanical deformations on glass surfaces near the elastic-plastic load boundary have been measured on various glasses by nanoscratching using an atomic force microscope ( AFM) to mimic the mechanical interactions of polishing particles during optical polishing. Nanoscratches were created in air and aqueous environments using a 150-nm radius diamond-coated tip on polished fused silica, borosilicate, and phosphate glass surfaces; the topology of the nanoscratches were then characterized by AFM. Using load ranges expected on slurry particles during glass polishing (0.05-200 μN), plastic-type scratches were observed with depths in the nm range. Nanoscratching in air generally showed deeper & narrower scratches with more pileup compared to nanoscratching in water, especially on fused silica glass. The critical load needed to observe plastic deformation was determined to range from 0.2-1.2 μN for the three glasses. For phosphate glass, the load dependence of the removal depth was consistent with that expected from Hertzian mechanics. However, for fused silica and borosilicate glass in this load range, the deformation depth showed a weak dependence with load. Using a sub- Tg annealing technique, material relaxation was observed on the nanoscratches, suggesting that a significant fraction of the deformation was due to densification on fused silica and borosilicate glass. Repeated nanoscratching at the same location was utilized for determining the effective incremental plastic removal depth. The incremental removal depth decreased with increase in number of passes, stabilizing after ~10 passes. In water, the removal depths were determined as 0.3-0.55 nm/pass for fused silica, 0.85 nm/pass for borosilicate glass, and 2.4 nm/pass for phosphate glass. The combined nanoscratching results were utilized to define the composite removal function (i.e., removal depth) for a single polishing particle as a function of load, spanning the chemical to the plastic removal regimes. This removal function serves as an important set of parameters in understanding material removal during polishing and the resulting workpiece surface roughness. [ABSTRACT FROM AUTHOR]

Objective Type I interferon (IFN) signaling is regarded as a central pathogenic pathway in systemic lupus erythematosus (SLE). Specific inhibition of this pathway is a core area for the development of new therapies for SLE. This study was undertaken to clarify the pathogenic mechanism involved and to identify new therapeutic targets, using a high-throughput screening platform to determine novel regulators that contribute to the overactivation of the type I IFN signaling pathway in SLE. Methods A high-throughput IFN-stimulated response element (ISRE)-luciferase assay was used to screen for candidate genes that regulate the IFN signaling pathway. Western blotting was used to confirm the regulatory function of CDK1. SYBR Green quantitative reverse transcriptase-polymerase chain reaction was used to detect the expression of individual IFN-stimulated genes (ISGs). The differential expression of CDK1 and ISGs in SLE patients and healthy controls was analyzed using RNA sequencing data and a microarray. Results The high-throughput ISRE-luciferase assay revealed that CDK1 enhanced type I IFN signaling. Consistent with this finding, CDK1 promoted the type I IFN-induced phosphorylation of STAT-1 and the up-regulated expression of ISGs. CDK1 expression was elevated in peripheral blood mononuclear cells (PBMCs) and kidney biopsy specimens from SLE patients and correlated positively with their IFN scores. A CDK1 inhibitor reduced the expression of ISGs in PBMCs from SLE patients and in renal cells from mice with lupus. Conclusion Our findings indicate that CDK1 is a positive regulator of the IFN signaling pathway. The overexpression of CDK1 might contribute to the abnormally amplified type I IFN signaling in SLE, and the inhibition of CDK1 could be used to down-regulate type I IFN signaling in SLE. [ABSTRACT FROM AUTHOR]

Aim To identify whether an isolated single umbilical artery (ISUA) impacts pregnancy outcome and delivery mode in single and full-term births. Methods A retrospective study was carried out on 93 592 pregnant women (singleton pregnancy; full-term birth; no known fetal chromosomal and structural anomalies) who gave birth between January 2011 and January 2012 in 39 hospitals within China. Pregnancy outcomes and modes of delivery were compared between research (313 cases with ISUAs) and comparison groups (1 252 cases with three-vessel cords in a 1:4 ratio randomly matched by parity). Results The birth weights (3264.71 ± 469.95 g vs 3340.76 ± 434.25 g, P = 0.001), birth lengths (48.51± 2.84 cm vs 49.99± 1.65cm, P = 0.000), placental weights (511.31± 76.43 g vs 545.31± 85.06 g, P = 0.002), umbilical cord lengths (52.64 ± 8.82 cm vs 54.08± 7.81cm, P = 0.002) and Apgar scores within one min of birth (8.83 ± 0.96 vs 9.57 ± 0.75, P = 0.000) of newborn infants were significantly lower in the research than the comparison group; the incidence of small for gestational age (10.94% vs 5.39%, P = 0.000) and low birth weight infants (6.69% vs 1.98%, P = 0.000) were significantly higher in the research group. There was no significant difference in fetal/placental weight, incidence of velamentous cord insertions, 1 min Apgar score < 7, 5 min Apgar score < 7 or vaginal or emergency cesarean delivery rates as a result of fetal factors between the two groups. Conclusion An ISUA is associated with an adverse pregnancy outcome; however does not decrease the rate of vaginal delivery in full-term births. [ABSTRACT FROM AUTHOR]

Objective Diffuse alveolar hemorrhage (DAH) is a rare but life-threatening complication of systemic lupus erythematosus (SLE). Pristane-treated B6 mice develop severe DAH within 2 weeks of treatment. MicroRNA-155 (miR-155) is a pleiotropic microRNA that plays a crucial role in the regulation of immune responses. Recent studies have revealed a pathogenic role of miR-155 in various autoimmune disorders. The purpose of this study was to examine the role of miR-155 in the development of DAH in pristane-induced lupus using miR-155-knockout (miR-155−/−) mice and miR-155 antagomir to silence miR-155. Methods DAH was induced by an intraperitoneal injection of 0.5 ml of pristane. MicroRNA-155 antagomir was administered intravenously to silence miR-155 expression. Lung tissues were collected for RNA extraction and were embedded in paraffin for sectioning. Gene expression profiling data were analyzed using Ingenuity Pathway Analysis. Real-time quantitative polymerase chain reaction analysis was used for single-gene validation. Luciferase reporter assay and argonaute 2 immunoprecipitation were performed for target validation. Results MicroRNA-155 expression was significantly increased during the development of DAH. Disease progression was reduced in miR-155−/− mice as well as by in vivo silencing of miR-155 using a miR-155 antagomir. MicroRNA-155 silencing dampened pristane-induced ectopic activation of multiple inflammatory pathways and reduced the expression of proinflammatory cytokines. Several negative regulators of NF-κB signaling were inhibited by pristane and were reactivated in miR-155−/− mice. In particular, the antiinflammatory factor peroxisome proliferator-activated receptor α was identified as a direct target of miR-155. Conclusion MicroRNA-155 promotes pristane-induced lung inflammation. It contributes to ectopic activation of NF-κB signaling pathways by targeting multiple negative regulators. MicroRNA-155 antagomir may be a promising therapeutic strategy for treating acute lung inflammation in lupus. [ABSTRACT FROM AUTHOR]

Presented herein are two luminescent magnesium coordination polymers (Mg-CPs), namely [Mg2(H2O)2(2-NDC)4(1,10-phen)2] ( 1) and [Mg2(H2O)(1,4-NDC)2(1,10-phen)] ( 2), in which 2-NDCH=2-naphthalenecarboxylic acid, 1,4-NDCH2=1,4-naphthalene dicarboxylic acid, and 1,10-phen=1,10-phenanthroline. Based on the mixed ligands, the title compounds exhibit linker-based photoluminescence (PL) properties thanks to the unique configuration of the Mg2+ ions. The two compounds show interesting dual emission on excitation of the different luminophores of the mixed linkers. In particular, the emissions of compound 2 could be tuned from green to yellow simply by varying the excitation energies. Furthermore, 2 could be excited by using a commercial λ=450 nm blue LED chip to generate white-light emission, which allows the fabrication of a white-light-emitting diode (WLED) with 20 lm W−1 luminous efficacy. This work may provide a new method for designing tunable PL CPs by using the low-cost and abundant magnesium ion. [ABSTRACT FROM AUTHOR]

Objective Systemic lupus erythematosus (SLE) is characterized by the uncontrolled production of inflammatory cytokines, among which type I interferon (IFN) is recognized as a crucial pathogenic factor. The expression of microRNA-146a (miR-146a) is reduced in the white blood cells of SLE patients and accounts for their overactivated inflammatory responses. However, the mechanism of the reduction of miR-146a is still not fully understood. This study was undertaken to test whether the key pathogenic cytokine, type I IFN, is responsible for the dysregulation of miR-146a in SLE. Methods Gene and protein expression was measured in all cells by reverse transcription-quantitative polymerase chain reaction, Northern blotting, or Western blotting. In THP-1 cells, expression of monocyte chemotactic protein-induced protein 1 (MCPIP-1) was knocked down with a lentivirus encoding a short hairpin RNA targeting MCPIP1. The cells were pretreated with type I IFN and assessed for gene expression levels of miR-146a. White blood cells from patients with SLE were analyzed for the expression of the IFN-inducible genes MCPIP1 and miR-146a, and the gene expression data were compared for correlation. Results Pretreatment of THP-1 cells with type I IFN attenuated the induction of miR-146a posttranscriptionally, by down-regulating the expression of pre-miR-146a but not pri-miR-146a or its original unspliced transcript. Expression of MCPIP-1, which was enhanced by type I IFN, was found to be responsible for the inhibition of miR-146a. In white blood cells from patients with SLE, MCPIP1 expression was elevated, and its expression correlated positively with the IFN score and negatively with the miR-146a transcript level. Conclusion Type I IFN inhibits the maturation of miR-146a through the up-regulation of MCPIP-1, and thus contributes to the uncontrolled inflammation and excessive inflammatory gene expression in SLE. [ABSTRACT FROM AUTHOR]

The chemical characteristics and the proposed formation mechanisms of the modified surface layer (called the Beilby layer) on polished fused silica glasses are described. Fused silica glass samples were polished using different slurries, polyurethane pads, and at different rotation rates. The concentration profiles of several key contaminants, such as Ce, K, and H, were measured in the near surface layer of the polished samples using Secondary Ion Mass Spectroscopy ( SIMS). The penetration of K, originating from KOH used for pH control during polishing, decreased with increase in polishing material removal rate. In contrast, penetration of the Ce and H increased with increase in polishing removal rate. In addition, Ce penetration was largely independent of the other polishing parameters (e.g., particle size distribution and the properties of the polishing pad). The resulting K concentration depth profiles are described using a two-step diffusion process: (1) steady-state moving boundary diffusion (due to material removal during polishing) followed by (2) simple diffusion during ambient postpolishing storage. Using known alkali metal diffusion coefficients in fused silica glass, this diffusion model predicts concentration profiles that are consistent with the measured data at various polishing material removal rates. On the other hand, the observed Ce profiles are inconsistent with diffusion based transport. Rather we propose that Ce penetration is governed by the ratio of Ce-O-Si and Si-O-Si hydrolysis rates; where this ratio increases with interface temperature (which increases with polishing material removal rate) resulting in greater Ce penetration into the Beilby layer. Calculated Ce surface concentrations using this mechanism are in good agreement to the observed change in measured Ce surface concentrations with polishing material removal rate. These new insights into the chemistry of the Beilby layer, combined together with details of the single particle removal function during polishing, are used to develop a more detailed and quantitative picture of the polishing process and the formation of the Beilby layer. [ABSTRACT FROM AUTHOR]

Localized infrared (IR) laser heating of fused silica optics has proven highly effective in reducing or removing surface flaws, which tend to limit performance in high power laser systems. Here, we present both simulation and experimental results to examine the use of IR laser light to polish, anneal, and micro-shape fused silica surfaces used in high power laser systems. We show how the resulting material response can be tuned by considering the temperature-dependent optical constants of the material and choosing the appropriate laser parameter set. For example, non-evaporative laser polishing of glass surfaces to heal crack networks is shown most effective when using mid-IR lasers, which lead to laser energy coupling up to ≈1 mm in depth. In contrast, long-wave IR light tuned to the Restrahlen frequency of the material is shown to evaporate material most efficiently with penetration depths of <1 μm. Through calibrated, time-resolved thermal imaging we are able to monitor the laser polishing process, to control material response. The results of our studies can be applied beyond the practical application of damage mitigation in high energy pulsed laser systems to any which require laser-smoothing and shaping of silica surfaces. [ABSTRACT FROM AUTHOR]