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IMPORTANCE: In several randomized clinical trials, endovascular thrombectomy led to better functional outcomes than conventional treatment at 90 days poststroke in patients with acute basilar artery occlusion. However, the long-term clinical outcomes of these patients have not been well delineated. OBJECTIVE: To evaluate 1-year clinical outcomes in patients with acute basilar artery occlusion following endovascular thrombectomy vs control. DESIGN, SETTING, AND PARTICIPANTS: This study is an extension of the ATTENTION trial, a multicenter, randomized clinical trial. Patients were included between February 2021 and January 2022, with 1-year follow-up through April 2023. This multicenter, population-based study was conducted at 36 comprehensive stroke sites. Patients with acute basilar artery occlusion within 12 hours of estimated symptom onset were included. Of the 342 patients randomized in the ATTENTION trial, 330 (96.5%) had 1-year follow-up information available. EXPOSURES: Endovascular thrombectomy (thrombectomy group) vs best medical treatment (control group). MAIN OUTCOMES AND MEASURES: The primary outcome was defined as a score of 0 to 3 on the modified Rankin Scale (mRS) at 1 year. Secondary outcomes were functional independence (mRS score 0-2), excellent outcome (mRS score 0-1), level of disability (distribution of all 7 mRS scores), mortality, and health-related quality of life at 1 year. RESULTS: Among 330 patients who had 1-year follow-up data, 227 (68.8%) were male, and the mean (SD) age was 67.0 (10.7) years. An mRS score 0 to 3 at 1 year was achieved by 99 of 222 patients (44.6%) in the thrombectomy group and 21 of 108 (19.4%) in the control group (adjusted rate ratio, 2.23; 95% CI, 1.51-3.29). Mortality at 1 year compared with 90 days was more frequent in both the thrombectomy group (101 of 222 [45.5%] vs 83 of 226 [36.7%]) and the control group (69 of 108 [63.9%] vs 63 of 114 [55.3%]). Excellent outcome (mRS score 0-1) at 1 year compared with 90 days increased in the thrombectomy group (62 of 222 [27.9%] vs 45 of 226 [19.9%]) but not in the control group (9 of 108 [8.3%] vs 9 of 114 [7.9%]) resulting in a magnified treatment benefit. CONCLUSIONS AND RELEVANCE: Among patients with basilar artery occlusion within 12 hours of onset, the benefits of endovascular thrombectomy at 1 year compared with 90 days were sustained for favorable (mRS score 0-3) outcome and enhanced for excellent (mRS score 0-1) outcome.

Matching the terrestrial laser scan point clouds with the unmanned aerial oblique photography point clouds of high-rise irregular buildings can make them complementary. The challenge lies in the different sources and qualities, besides arbitrary angular deviations of the two types of point clouds. We propose a registration method based on point and line features, which automatically recognises the features of these point clouds using normal vectors and 3D-Harris, and solves the registration parameters through rigorous adjustment. The registration model, process and method are introduced. Finally, through the analysis of real case examples, it was found that the registration result of this method was better than the traditional Iterative Closest Point (ICP) in the analysed cases, the proposed registration method not only exhibits good automation but also has the ability to ignore various differences in heterogeneous point clouds, thereby improving the accuracy and efficiency of registration for such point clouds.

Background: Diagnosis of fever of unknown origin remains challenge for pediatricians. Lymphadenopathy is a separate entity that mainly originates from infection or malignancy. Methods: 168 patients with FUO accompanied by lymphadenectasis were reviewed. 33 lymph node tissue samples were examined by mNGS. Differences in clinical characteristics were compared among different disease groups. The value of mNGS in diagnosing and improving the clinical situation was assessed. Results: Multivariate analysis revealed that hepatosplenomegaly and LDH levels were associated with infectious diseases. Arthralgia was correlated with non-infectious inflammatory diseases. Weight loss and a node located in supraclavicular region may indicate neoplastic diseases. mNGS-positive rate was 60.60%, higher than that obtained with traditional methods. Treatment for 3/4 patients was adjusted according to the pathogen detected by mNGS, and antibiotics uses was discontinued or degraded in over 1/2 of the patients according to mNGS results. Conclusions: Clinical characteristics of children with lymphadenopathy related to FUO have limited diagnostic value for distinguishing different kinds of diseases, while mNGS of lymph node tissue serves as a useful tool for identifying infectious diseases, especially those caused by rare pathogens. mNGS results can lead to not only adjustments in targeted treatment but also further confirmation of underlying diseases. Impact Statement:

The clinical features of children with FUO and lymphadenopathy differ according to disease group,although multivariate analysis indicated little diagnostic value for these features.

mNGS on lymph node tissue from children with FUO may serve as a efficient tool for distinguishing infectious diseases from other diseases. This is especially useful when a diagnosis cannot be determined with traditional methods.

mNGS targeted treatment can be administered in a timely manner and some underlying diseases can be indicated.

Most aquatic plants applied to ecological restoration have demonstrated a clonal growth pattern. The risk-spreading strategy plays a crucial role in facilitating clonal plant growth under external environmental stresses via clonal integration. However, the effects of different concentrations of nanoplastics (NPs) on the growth traits of clonal aquatic plants are not well understood. Therefore, this study aimed to investigate the impact of NPs exposure on seedlings of parent plants and connected offspring ramets. A dose response experiment (0.1, 1, and 10 mg L–1) showed that the growth of Eichhornia crassipes(water hyacinth) was affected by 100 nm polystyrene nanoplastics after 28 days of exposure. Tracer analysis revealed that NPs are accumulated by parent plants and transferred to offspring ramets through stolon. Quantification analysis showed that when the parent plant was exposed to 10 mg L–1NPs alone for 28 days, the offspring ramets contained approximately 13 ± 2 μg/g NPs. In the case of connected offspring ramets, leaf and root biomass decreased by 24%–51% and 32%–51%, respectively, when exposed to NP concentrations ranging from 0.1 to 10 mg L–1. Excessive enrichment of NPs had a detrimental effect on the photosynthetic system, decreasing the chlorophyll content and nonphotochemical quenching. An imbalance in the antioxidant defense systems, which were unable to cope with the oxidative stress caused by NP concentrations, further damaged various organs. The root system can take up NPs and then transfer them to the offspring through the stolon. Interference effects of NPs were observed in terms of root activity, metabolism, biofilm composition, and the plant’s ability to purify water. However, the risk-spreading strategy employed by parent plants (interconnected offspring ramets) offered some relief from NP-induced stress, as it increased their relative growth rate by 1 to 1.38 times compared to individual plants. These findings provide substantial evidence of the high NP enrichment capacity of E. crassipesfor ecological remediation. Nevertheless, we must also remain aware of the environmental risk associated with the spread of NPs within the clonal system of E. crassipes, and contaminated cloned individuals need to be precisely removed in a timely manner to maintain normal functions.

Background: The correlation between the gut microbiota and airway inflammation in childhood allergic rhinitis (AR), particularly concerning allergen exposure, remains insufficiently explored. This study aimed to link gut microbiota changes with house dust mite (HDM)-specific IgE responses in pediatric AR. Methods: Using metagenomic shotgun sequencing, we compared the fecal microbiota of 60 children with HDM-AR to 48 healthy controls (HC), analyzing the link to IgE reactions. We examined the effects of oral Escherichia (E.) fergusoniitreatment in mice sensitized with ovalbumin and HDM on allergic symptoms, mucosal cell infiltration, Th1/Th2/Tregs balance in the spleen, serum cytokine levels, and E. fergusoniipresence in feces. Results: Children with HDM-AR have a less diverse gut microbiome and lower levels of E. fergusoniicompared to controls, with a negative correlation between E. fergusoniiabundance and HDM-specific IgE levels. In mice sensitized with OVA and HDM, oral administration of E. fergusoniiimproved allergic symptoms, reduced nasal eosinophils/mast cells infiltration and adjusted Th cell populations towards a non-allergic profile in splenic lymphocytes with exception of IFN-γ change in serum. Conclusion: These findings underline the potential of targeting gut microbiota, particularly E. fergusonii, in managing childhood HDM-AR, suggesting a promising approach for future interventions. Impact:

The composition and distribution of gut microbiota in children with HDM-AR are significant changed.

The abundance of Escherichiagenus is decreased in HDM-AR children.

HDM-specific IgE levels are strongly negatively associated with E. fergusoniiabundance.

Oral administration of E. fergusoniieffectively suppresses allergic responses in murine model.

These findings offer novel insights into the diagnosis and treatment of HDM-AR, which suggested that E. fergusoniiholds promise as a potential therapeutic avenue for managing HDM-AR.

Whole-exome sequencing of two unrelated kindreds with systemic autoimmune disease featuring antinuclear antibodies with IgG4 elevation uncovered an identical ultrarare heterozygous TNIP1Q333Pvariant segregating with disease. Mice with the orthologous Q346P variant developed antinuclear autoantibodies, salivary gland inflammation, elevated IgG2c, spontaneous germinal centers and expansion of age-associated B cells, plasma cells and follicular and extrafollicular helper T cells. B cell phenotypes were cell-autonomous and rescued by ablation of Toll-like receptor 7 (TLR7) or MyD88. The variant increased interferon-β without altering nuclear factor kappa-light-chain-enhancer of activated B cells signaling, and impaired MyD88 and IRAK1 recruitment to autophagosomes. Additionally, the Q333P variant impaired TNIP1 localization to damaged mitochondria and mitophagosome formation. Damaged mitochondria were abundant in the salivary epithelial cells of Tnip1Q346Pmice. These findings suggest that TNIP1-mediated autoimmunity may be a consequence of increased TLR7 signaling due to impaired recruitment of downstream signaling molecules and damaged mitochondria to autophagosomes and may thus respond to TLR7-targeted therapeutics.

Effective soil particle size composition can more realistically reflect the particle size sorting process of erosion. To reveal the individual contributions of rainfall intensity and slope to splash erosion, and to distinguish the enrichment ratio of each size and the critical size in splash, loessial soil collected on the Loess Plateau in May 2019 was tested under different rainfall intensities (60, 84, 108, 132, 156 mm h−1) and slopes (0°, 5°, 10°, 15°, 20°). The results demonstrated that 99% of splash mass was concentrated in 0–0.4 m. Rainfall intensity was the major factor for splash according to the raindrop generation mode by rainfall simulator nozzles. The contributions of rainfall intensity to splash erosion were 82.72% and 93.24%, respectively in upslope and downslope direction. The mass percentages of effective clay and effective silt were positively correlated with rainfall intensity, while the mass percentages of effective very fine sand and effective fine sand were negatively correlated with rainfall intensity. Opposite to effective very fine sand, the mass percentages of effective clay significantly decreased with increasing distance. Rainfall intensity had significant effects on enrichment ratios, positively for effective clay and effective silt and negatively for effective very fine sand and effective fine sand. The critical effective particle size in splash for loessial soil was 50 µm.

Mesenchymal stem cells (MSCs) influence T cells in health, disease and therapy through messengers of intercellular communication including extracellular vesicles (EVs). Apoptosis is a mode of cell death that tends to promote immune tolerance, and a large number of apoptotic vesicles (apoVs) are generated from MSCs during apoptosis. In an effort to characterize these apoVs and explore their immunomodulatory potential, here we show that after replenishing them systemically, the apoV deficiency in Fasmutant mice and pathological lymphoproliferation were rescued, leading to the amelioration of inflammation and lupus activity. ApoVs directly interacted with CD4+T cells and inhibited CD25 expression and IL-2 production in a dose-dependent manner. A broad range of Th1/2/17 subsets and cytokines including IFNγ, IL17A and IL-10 were suppressed while Foxp3+cells were maintained. Mechanistically, exposed phosphatidylserine (PtdSer/PS) on apoVs mediated the interaction with T cells to disrupt proximal T cell receptor signaling transduction. Remarkably, administration of apoVs prevented Th17 differentiation and memory formation, and ameliorated inflammation and joint erosion in murine arthritis. Collectively, our findings unveil a previously unrecognized crosstalk between MSC apoVs and CD4+T cells and suggest a promising therapeutic use of apoVs for autoimmune diseases.

For decades, displacement detection based on global navigation satellite system (GNSS) has increasingly been an important part of deformation monitoring for applications, such as dams, bridges, and high-rise buildings. Automatic identification and extraction of 3-D displacements from GNSS kinematic positioning can provide a basis for emergency response decision-making and play a crucial role in natural and secondary disasters. However, due to the limitation of single epoch positioning accuracy, automatic detection of displacement from GNSS kinematic positioning results is still a challenge. To resolve this, we propose an enhanced $K$ -means clustering method to detect displacements from GNSS kinematic positioning, which identifies the displacement by clustering and obtains displacements from adjacent clusters. Results from simulation and field experiments have demonstrated the effectiveness of the proposed method. The accuracy of 3-D displacement extraction from GNSS real-time kinematic (RTK) positioning can reach millimeter level.

Objective: Isocitrate dehydrogenase gene (IDH) mutations are associated with tumor angiogenesis and therefore play an important role in glioma management. This study compared the performance of tumor blood vessels counted from contrast-enhanced 3D brain volume (3D-BRAVO) sequence and dynamic contrast-enhanced (DCE) MRI in differentiating IDH1 status in gliomas. Methods: Forty-four glioma patients [16 with IDH1 mutant-type (IDH1-MT), 28 with IDH1 wild-type (IDH1-WT)] were retrospectively analyzed. A blood vessel entering a tumor was defined as an intratumoral vessel; a blood vessel adjacent to the edge of a tumor was defined as a peritumoral vessel. Combined vessels were defined as the sum of the intratumoral and peritumoral vessels. DCE-derived metrics of tumor were normalized to the contralateral normal-appearing white matter. Results: Intratumoral, peritumoral, and combined tumor blood vessels were all significantly different between IDH1-MT and IDH1-WT gliomas, and the range of area under curves (AUCs) was 0.816–0.855. For DCE-derived parameters, cerebral blood volume, cerebral blood flow, mean transit time, and volume transfer constant were significantly different between IDH1-MT and IDH1-WT gliomas, and the range of AUCs was 0.703–0.756. Combined vessels possessed the best performance for identifying IDH1 mutations in gliomas (AUC: 0.855, sensitivity: 0.857, specificity: 0.812, P<0.001). Conclusion: The number of tumor blood vessels has comparable diagnostic performance with DCE-derived parameters for differentiating IDH1 mutations and can serve as a potential imaging biomarker to reflect IDH1 mutations in gliomas.

Although circumstantial evidence supports enhanced Toll-like receptor 7 (TLR7) signalling as a mechanism of human systemic autoimmune disease1–7, evidence of lupus-causing TLR7gene variants is lacking. Here we describe human systemic lupus erythematosus caused by a TLR7gain-of-function variant. TLR7 is a sensor of viral RNA8,9and binds to guanosine10–12. We identified a de novo, previously undescribed missense TLR7Y264Hvariant in a child with severe lupus and additional variants in other patients with lupus. The TLR7Y264Hvariant selectively increased sensing of guanosine and 2',3'-cGMP10–12, and was sufficient to cause lupus when introduced into mice. We show that enhanced TLR7 signalling drives aberrant survival of B cell receptor (BCR)-activated B cells, and in a cell-intrinsic manner, accumulation of CD11c+age-associated B cells and germinal centre B cells. Follicular and extrafollicular helper T cells were also increased but these phenotypes were cell-extrinsic. Deficiency of MyD88 (an adaptor protein downstream of TLR7) rescued autoimmunity, aberrant B cell survival, and all cellular and serological phenotypes. Despite prominent spontaneous germinal-centre formation in Tlr7Y264Hmice, autoimmunity was not ameliorated by germinal-centre deficiency, suggesting an extrafollicular origin of pathogenic B cells. We establish the importance of TLR7 and guanosine-containing self-ligands for human lupus pathogenesis, which paves the way for therapeutic TLR7 or MyD88 inhibition.

Genome editing through adeno-associated viral (AAV) vectors is a promising gene therapy strategy for various diseases, especially genetic disorders. However, homologous recombination (HR) efficiency is extremely low in adult animal models. We assumed that increasing AAV transduction efficiency could increase genome editing activity, especially HR efficiency, for in vivogene therapy. Firstly, a mouse phenylketonuria (PKU) model carrying a pathogenic R408W mutation in phenylalanine hydroxylase (Pah) was generated. Through co-delivery of the general AAV receptor (AAVR), we found that AAVR could dramatically increase AAV transduction efficiency in vitroand in vivo. Furthermore, co-delivery of SaCas9/sgRNA/donor templates with AAVR via AAV8 vectors increased indel rate over 2-fold and HR rate over 15-fold for the correction of the single mutation in PahR408Wmice. Moreover, AAVR co-injection successfully increased the site-specific insertion rate of a 1.4 kb PahcDNA by 11-fold, bringing the HR rate up to 7.3% without detectable global off-target effects. Insertion of PahcDNA significantly decreased the Phe level and ameliorated PKU symptoms. This study demonstrates a novel strategy to dramatically increase AAV transduction which substantially enhanced in vivogenome editing efficiency in adult animal models, showing clinical potential for both conventional and genome editing-based gene therapy.

Renal interstitial fibrosis (RIF) is an incurable pathological lesion in chronic kidney diseases. Pericyte activation is the major pathological characteristic of RIF. Fibroblast and macrophage activation are also involved in RIF. Studies have revealed that core fucosylation (CF), an important post-translational modification of proteins, plays a key role in pericyte activation and RIF by regulating multiple profibrotic signaling pathways as a hub-like target. Here, we reveal that mesenchymal stem cell (MSC)-derived exosomes reside specifically in the injured kidney and deliver microRNA (miR)-34c-5p to reduce cellular activation and RIF by inhibiting CF. Furthermore, we showed that the CD81-epidermal growth factor receptor (EGFR) ligand-receptor complex aids the entry of exosomal miR-34c-5p into pericytes, fibroblasts, and macrophages. Altogether, our findings reveal a novel role of MSC-derived exosomes in inhibiting multicellular activation via CF and provide a potential intervention strategy for renal fibrosis.

A novel complex comprising an ion pair of arginine–arginine carbamate is reported herein, which is isolated from an aqueous l-arginine solution after reacting with CO2. Its structure was unambiguously elucidated via single-crystal X-ray diffraction, and its phase purity was confirmed by powder X-ray diffraction (PXRD) analysis. Nuclear magnetic resonance (NMR) studies suggested that the arginine carbamate complex hydrolyzed in aqueous conditions with a rate directly proportional to its concentration. Furthermore, density functional theory (DFT) calculations revealed how the amino group acted as a nucleophile to attack CO2to enable the ion-pair formation through a proton transfer between the arginine and arginine carbamate. The discovery of the arginine–CO2adduct expands our understanding of CO2fixation and can lead to the development of new methods of implementing l-arginine or other amino acids for CO2capture technology.

Follicular helper T (TFH) cells are a specialized subset of CD4+T cells that essentially support germinal center responses where high-affinity and long-lived humoral immunity is generated. The regulation of TFHcell survival remains unclear. Here we report that TFHcells show intensified lipid peroxidation and altered mitochondrial morphology, resembling the features of ferroptosis, a form of programmed cell death that is driven by iron-dependent accumulation of lipid peroxidation. Glutathione peroxidase 4 (GPX4) is the major lipid peroxidation scavenger and is necessary for TFHcell survival. The deletion of GPX4 in T cells selectively abrogated TFHcells and germinal center responses in immunized mice. Selenium supplementation enhanced GPX4 expression in T cells, increased TFHcell numbers and promoted antibody responses in immunized mice and young adults after influenza vaccination. Our findings reveal the central role of the selenium–GPX4–ferroptosis axis in regulating TFHhomeostasis, which can be targeted to enhance TFHcell function in infection and following vaccination.

In this paper, the correlation analysis between mechanical fatigue properties and pore structure was performed on the self-compacting rubberised concrete (SCRC). Four-point bending destructive and non-destructive fatigue tests were conducted for obtaining mechanical properties of the SCRC, while the mercury intrusion porosimetry (MIP) test was applied to the pore structure analysis. Several parameters were utilised for the description of pore structure, including porosity, mean pore diameter, threshold, fractal dimension, actual minimum diameter and the most probable pore diameter. The Pearson formula was introduced for the study on the correlation among the fatigue life, the fatigue damage and different pore structure parameters. The experimental results show that the fatigue load has a strong effect on the pore structure change. As the damage developing, the pore structure of the SCRC deteriorated: the porosity, the mean pore diameter, the actual minimum diameter and the most probable pore diameter increase. Meanwhile, the capillary pore fractural dimension decreases slightly. On the basis of the factors, the parameters of pore structure can be served as indices for the fatigue life prediction. The correlation parameters between the fatigue life and the optimal parameters of pore structure (the porosity, the most probable pore diameter, the mean pore diameter and the mesopore fractural dimension) have been determined in this paper.

Rheumatic diseases reach across continents with some similarities as well as unique challenges. The intersection between genetic factors, environmental exposures and socioeconomic factors, as well as challenges, with delays in access to subspecialty care and medications, manifest in different ways. By understanding both the challenges and successes in different countries, while also recognizing the significant diversity both within and across continents, unified strategies to improve rheumatic disease outcomes and decrease disparities among the most vulnerable groups can be developed and disseminated.

Two bismuth(III) halides hybrids with room-temperature phosphorescence (RTP), namely, [BPy]2[Bi2Cl8(bpym)] (1, BPy = N-butylpyridinium) and [EPy]2[Bi2Cl8(bpym)] (2, EPy = N-ethylpyridinium), were synthesized and characterized. Structural comparison reveals that 1and 2possess similar anionic zigzaglike chain of [Bi2Cl8(bpym)]n2n–; however, different packing modes of anion/cations and thus different weak interactions. Interestingly, the utilization of pyridinium cations with different length of alkyl chain could tune the RTP behaviors efficiently. The RTP quantum yield (QY) is increased more than 5-fold from 1to 2probably due to more rigid structure of 2arising from the additional H-bond and anion−π interactions, as confirmed by Hirshfeld surfaces analyses and PLATONcalculations. Moreover, additional π–π interactions in 1could stabilize the triplet excitons, leading to an average lifetime of 1(11.36 ms at 77 K and 1.407 ms at 298 K) being higher than 2(0.3618 ms at 77 K and 0.07511 ms at 298 K). Density functional theory (DFT) calculations confirm that inorganic moiety to organic ligand charge-transfer (IOCT) is involved in the phosphorescence process. The present work provides a new sight into the design of RTP metal halides through studying the structure–RTP relationship.

To prevent and treat chronic diseases, including cancer, a global application of systems biology is needed. We report here a whole blood transcriptome test that needs only 50 μl of capillary (fingerprick) blood. This test is suitable for global applications because the samples are preserved at ambient temperature for up to 4 weeks and the RNA preservative inactivates all pathogens, enabling safe transportation. Both the laboratory and bioinformatic steps are automated and performed in a clinical lab, which minimizes batch effects and creates unbiased datasets. Given its clinical testing performance and accessibility to traditionally underrepresented and diverse populations, this test offers a unique ability to reveal molecular mechanisms of disease and enable longitudinal, population-scale studies.

Systemic lupus erythematosus (SLE), a common lethal autoimmune disease, is characterized by effector/regulatory T cells imbalance. Current therapies are either inefficient or have severe side effects. MicroRNA-125a (miR-125a) can stabilize Treg-mediated self-tolerance by targeting effector programs, but it is significantly downregulated in peripheral T cells of patients with SLE. Therefore, overexpression of miR-125a may have therapeutic potential to treat SLE. Considering the stability and targeted delivery of miRNA remains a major challenge in vivo, we constructed a monomethoxy (polyethylene glycol)-poly(d,l-lactide-co-glycolide)-poly(l-lysine) (mPEG-PLGA-PLL) nanodelivery system to deliver miR-125a into splenic T cells. Results demonstrate that miR-125a-loaded mPEG-PLGA-PLL (PEALmiR-125a) nanoparticles (NPs) exhibit good biocompatibility and protect miR-125a from degradation, thereby prolonging the circulatory time of miRNA in vivo. In addition, PEALmiR-125aNPs are preferentially enriched in a pathological spleen and efficiently deliver miR-125a into the splenic T cells in SLE mice models. The PEALmiR-125aNPs treatment significantly alleviates SLE disease progression by reversing the imbalance of effector/regulatory T cells. Collectively, the PEALmiR-125aNPs show excellent therapeutic efficacy and safety, which may provide an effective treatment for SLE.

Atomically smooth hexagonal boron nitride (h-BN) films are needed for emerging applications of two-dimensional (2D) devices based on van der Waals heterostructures. Currently, it is difficult to prepare high-quality, large-area single crystalline h-BN monolayers by standard chemical vapor deposition. Here, we develop a free-molecular-flow growth model for h-BN synthesis by constructing a narrow gap within Cu/supporting substrates stacking, improving upon earlier studies by increasing domain sizes up to ∼80 μm. Further, the edges of h-BN varying from negative-curved to straight, positive-curved, and even round were reliably modified by varying the precursor heating temperature. Moreover, the merging processes of h-BN films are experimentally investigated, demonstrating the Bravais law is applicable for the coalescence of h-BN domains. This work not only offers a promising strategy for high-quality h-BN growth and insight into its growth dynamics which sheds light on reliable edge controllability and possible properties modification of other 2D crystals, but also enriches the understanding of the classical crystal growth theory and extends its applicability into the growth and evolution of 2D crystals.

Neuropsychiatric systemic lupus erythaematosus (NP-SLE) is one of the major manifestations of lupus. However, the mechanisms involved in NP-SLE are still largely unknown. The abnormal activation of the type I IFN signalling pathway is involved in SLE pathogenesis and is linked to NP-SLE, but the effect of IFN-α on NP-SLE encephalopathy has not been systematically studied. An intravenous injection of Adv-IFN-α (10 mice, 10 × 109vp) was administered to the IFN-α-treated group, and Adv-ctrl (10 mice, 10 × 109vp) (ViGene Biosciences, China) was administered to the control group. Gene expression was determined by real-time quantitative polymerase chain reaction (RT-qPCR). Enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies in the serum, and urinary protein levels were measured with a BCA Protein Assay kit. Haematoxylin-eosin (H&E) and periodic acid-Schiff (PAS)-light green staining were used for kidney histology. The elevated plus-maze test, novelty-suppressed feeding assay, open-field test, tail suspension test, social dominance tube test, three-chamber social interaction test, step-down passive avoidance test and novelty Y-maze task were used to assess behaviour. In this study, we performed a series of behavioural tests to assess the neuropsychiatric phenotypes of IFN-α-treated NZB/NZW F1 mice and found that these mice developed a series of mental disorders such as anxiety-like phenotypes, depression-like phenotypes, deficits in sociability and cognitive impairments, which mimic the neuropsychiatric manifestations of NP-SLE, with a consistent onset and progression. Our research verified that IFN-α plays a critical role in NP-SLE and provides a comprehensive NP-SLE mouse model for dissecting the mechanisms of NP-SLE and developing novel therapies for intervention.

X-ray detection has been extensively applied in various fields including medical imaging, security detection, and industrial non-destructive testing. Recently, organic-metal halide perovskites (OMHP) are being under the spotlight of the academia in X-ray detection and imaging, owing to their outstanding photoelectric properties such as high photoluminescence quantum yield, large X-ray attenuation coefficient, high carrier mobility-lifetime (μτ) product and high defect-tolerant nature as well as low-cost raw materials and facile preparation technology. The reported perovskite X-ray detectors have displayed superb sensitivity and high-spatial-resolution X-ray imaging, promisingly challenging the traditional commercial X-ray detectors based on Si, α-Se or CsI:TI. Inspired by these exciting results, we summarize the recent progress of OMHP X-ray detectors. At first, we briefly introduce the working mechanism of indirect/direct X-ray detectors and the corresponding device structure, followed by a detailed discussion of the performance parameters of X-ray detectors. Then, we further demonstrate the achievements of OMHP in X-ray detection and imaging in terms of device type, perovskite composition, film species, fabrication technique, and optimized strategies, where the interplay between perovskite constituent/type, preparation technology and device performance are strongly emphasized. Finally, the challenges and prospects of OMHP-based X-ray detectors for the future development toward the commercialized application are proposed.

Systemic Lupus Erythematosus (SLE) is a multifactorial autoimmune disease that arises from a dynamic interplay between genetics and environmental triggers. The advent of sophisticated genomics technology has catalyzed a shift in our understanding of disease etiology, spotlighting the pivotal role of non-coding DNA variants in SLE pathogenesis. In this review, we present a comprehensive examination of the non-coding variants associated with SLE, shedding light on their role in influencing disease risk and progression. We discuss the latest methodological advancements that have been instrumental in the identification and functional characterization of these genomic elements, with a special focus on the transformative power of CRISPR-based gene-editing technologies. Additionally, the review probes into the therapeutic opportunities that arise from modulating non-coding regions associated with SLE. Through an exploration of the complex network of non-coding DNA, this review aspires to decode the genetic puzzle of SLE and set the stage for groundbreaking gene-based therapeutic interventions and the advancement of precision medicine strategies tailored to SLE management.

Objective: Chronic kidney disease (CKD) patients with coronary artery disease (CAD) in the intensive care unit (ICU) have higher in-hospital mortality and poorer prognosis than patients with either single condition. The objective of this study is to develop a novel model that can predict the in-hospital mortality of that kind of patient in the ICU using machine learning methods. Methods: Data of CKD patients with CAD were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Boruta algorithm was conducted for the feature selection process. Eight machine learning algorithms, such as logistic regression (LR), random forest (RF), Decision Tree, K-nearest neighbors (KNN), Gradient Boosting Decision Tree Machine (GBDT), Support Vector Machine (SVM), Neural Network (NN), and Extreme Gradient Boosting (XGBoost), were conducted to construct the predictive model for in-hospital mortality and performance was evaluated by average precision (AP) and area under the receiver operating characteristic curve (AUC). Shapley Additive Explanations (SHAP) algorithm was applied to explain the model visually. Moreover, data from the Telehealth Intensive Care Unit Collaborative Research Database (eICU-CRD) were acquired as an external validation set. Results: 3590 and 1657 CKD patients with CAD were acquired from MIMIC-IV and eICU-CRD databases, respectively. A total of 78 variables were selected for the machine learning model development process. Comparatively, GBDT had the highest predictive performance according to the results of AUC (0.946) and AP (0.778). The SHAP method reveals the top 20 factors based on the importance ranking. In addition, GBDT had good predictive value and a certain degree of clinical value in the external validation according to the AUC (0.865), AP (0.672), decision curve analysis, and calibration curve. Conclusion: Machine learning algorithms, especially GBDT, can be reliable tools for accurately predicting the in-hospital mortality risk for CKD patients with CAD in the ICU. This contributed to providing optimal resource allocation and reducing in-hospital mortality by tailoring precise management and implementation of early interventions.

Background: The triglyceride–glucose (TyG) index is validated as a reliable biomarker of insulin resistance and an independent predictor of cardiovascular prognosis. However, the prognostic value of the TyG index in patients on dialysis with coronary artery disease (CAD) remained unexplored. This study aimed to determine the association between the TyG index and CAD severity and mortality in these patients. Methods: A total of 1061 dialysis patients with CAD were enrolled in this multi-center cohort study from January 2015 to June 2021. The extent and severity of CAD were evaluated using the multivessel disease and Gensini score (GS). Patients were followed up for all-cause death and cardiovascular death. Results: The multivariable logistic regression model indicated that the TyG index was significantly associated with multivessel disease (odds ratio [OR] 1.51, 95% confidence interval [CI] 1.18–1.94, P= 0.001), and high GS (OR 1.33, 95% CI 1.10–1.61, P= 0.003). After adjusting for baseline risk factors, the hazards of all-cause death and cardiovascular death were 1.23 (95% CI 1.06–1.43, P= 0.007), and 1.33 (95% CI 1.11–1.59, P= 0.002), independent of CAD severity. Restricted cubic spline analysis identified a dose–response association between the TyG index and both CAD severity and mortality (all Pfor nonlinearity > 0.05). When modeling the TyG index as a categorical variable, these independent associations remained. Subgroup analyses did not substantially modify the results. Furthermore, incorporating the TyG index into the existing risk prediction model improved the predictive accuracy for all-cause death and cardiovascular death, as evaluated by C-statistic, continuous net reclassification improvement, and integrated discrimination improvement. Conclusions: In patients on dialysis with CAD, the TyG index was significantly associated with more severe CAD as well as mortality. These results highlight the clinical importance of the TyG index for assessing CAD severity and risk stratification in patients on dialysis with CAD.

Wu et al.developed a rapid and low-cost method to screen for biomarkers for SLE by combining a phage displayed random peptide library (Ph.D. 12) and deep sequencing. Through statistical analysis and ELISA validation, a four-peptide panel was determined, which has the capability to differentiate SLE patients from health controls with high confidence.

A series of controlled grinding experiments, utilizing loose or fixed abrasives of either alumina or diamond at various particle sizes, were performed on a wide range of optical workpiece materials [single crystals of Al_2O_3 (sapphire), SiC, Y_3Al_5O_12 (YAG), CaF_2, and LiB_3O_5 (LBO); a SiO_2−Al_2O_3−P_2O_5−Li_2O glass ceramic (Zerodur); and glasses of SiO_2:TiO_2 (ULE), SiO_2 (fused silica), and P_2O_5−Al_2O_3−K_2O−BaO (phosphate)]. The material removal rate, surface roughness, and morphology of surface fractures were measured. Separately, Vickers indentation was performed on the workpieces, and the depths of various crack types as a function of applied load was measured. Single pass grinding experiments showed distinct differences in the spatial pattern of surface fracturing between the loose alumina abrasive (isolated indent-type lateral cracking) and the loose or fixed diamond abrasive (scratch-type elongated lateral cracking). Each of the grinding methods had a removal rate and roughness that scaled with the lateral crack slope, s_ℓ (i.e., the rate of increase in lateral crack depth with the applied load) of the workpiece material. A grinding model (based on the volumetric removal of lateral cracks accounting for neighboring lateral crack removal efficiency and the fraction of abrasive particles leading to fracture initiation) and a roughness model (based on the depth of lateral cracks or the interface gap between the workpiece and lap) are shown to quantitatively describe the material removal rate and roughness as a function of workpiece material, abrasive size, applied pressure, and relative velocity. This broad, multiprocess variable grinding model can serve as a predictive tool for estimating grinding rates and surface roughness for various grinding processes on different workpiece materials.

Cultivation of the mangrove rhizosphere soil-derived fungus Penicillium janthinellumHK1-6 with NaBr led to the isolation of two new brominated azaphilones, penicilones G and H (5, 6), two new tricyclic polyketides, penijanthinones A and B (7, 8), and two known azaphilones, penicilones A and B (1, 2). The planar structures and relative configurations of the new compounds were elucidated using comprehensive spectroscopic methods including 1D and 2D NOE spectra. Their absolute configurations were determined by chemical conversions, TDDFT ECD calculations, and comparisons of their ECD spectra. Interestingly, the NaBr-induced brominated azaphilones (5, 6) had the opposite configuration at C-7 compared to the chloro analogues (3, 4) produced by this fungus cultivated with sea salt. Ester hydrolysis of penicilone B (2) afforded the carboxylic acid side chain 2,4-dimethyldec-2-enoic acid (9), with a 4Sconfiguration assigned by its specific rotation. Penicilone H (6) showed antibacterial activity with MIC values ranging from 3.13 to 12.5 μg/mL.

Self-improving collodion ichthyosis (SICI) is a relatively rare subtype of autosomal recessive congenital ichthyosis (ARCI) that is often characterized by a collodion baby (CB) phenotype at birth. A newborn girl, just 1 hour old, presented with taut, shiny, thick yellow crusts, like parchment, and scales on her trunk and upper limbs. The tightening effect had caused both upper eyelids to appear everted, and her lips and auricles were deformed. Based on whole-exome sequencing and examination of the clinical phenotype, the patient was diagnosed with ARCI. After admission, the exposed mucosa was covered with a sterile Vaseline gauze dressing, and she was placed in an incubator set to a temperature of 32°C with a humidity level of 75%. One week later, the parchment-like scales had begun to flake off, and at the age of 3 weeks, all bodily skin appeared normal. SICI was diagnosed. After discharge, the patient was followed up to 3 months of age, at which time her growth and development were comparable to those of her peers. Clinicians should consider SICI as a possible diagnosis when analyzing the prognosis of patients with CB. Reducing water loss and maintaining the electrolyte balance are particularly important for SICI treatment.

Ultrafiltration failure is a major complication of long-term peritoneal dialysis, resulting in dialysis failure. Peritoneal fibrosis induced by continuous exposure to high glucose dialysate is the major contributor of ultrafiltration failure, for which there is no effective treatment. Overactivation of several signaling pathways, including transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor (PDGF) pathways, contribute to the development of peritoneal fibrosis. Therefore, simultaneously blocking multiple signaling pathways might be a potential novel method of treating peritoneal fibrosis. Previously, we showed that core fucosylation, an important posttranslational modification of the TGF-β1 receptors, can regulate the activation of TGF-β1 signaling in renal interstitial fibrosis. However, it remains unclear whether core fucosylation affects the progression of peritoneal fibrosis. Herein, we show that core fucosylation was enriched in the peritoneal membrane of rats accompanied by peritoneal fibrosis induced by a high glucose dialysate. Blocking core fucosylation dramatically attenuated peritoneal fibrosis in the rat model achieved by simultaneously inactivating the TGF-β1 and PDGF signaling pathways. Next the protective effects of blocking core fucosylation and imatinib (a selective PDGF receptor inhibitor) on peritoneal fibrosis were compared and found to exhibit a greater inhibitory effect over imatinib alone, suggesting that blocking activation of multiple signaling pathways may have superior inhibitory effects on the development of peritoneal fibrosis. Thus, core fucosylation is essential for the development of peritoneal fibrosis by regulating the activation of multiple signaling pathways. This may be a potential novel target for drug development to treat peritoneal fibrosis.

A series of hybrid tellurium chlorides based on ionic liquids (ILs), namely, α-[Bmim]2TeCl6(1, Bmim = 1-butyl-3-methyl imidazolium), β-[Bmim]2TeCl6(2), [HOOCMim]2TeCl6(3, HOOCMim = 1-carboxymethyl-3-methyl imidazolium), [Bzmim]2TeCl6(4, Bzmim = 1-benzyl-3-methyl imidazolium), [EPy]2TeCl6(5, EPy = 1-ethylpyridinium), [Bmmim]2TeCl6(6, Bmmim = 1-butyl-2,3-dimethyl imidazolium), have been synthesized and characterized. Different kinds of supramolecular networks have been obtained via self-assemblies of isolated [TeCl6]2–anions and various ionic liquid cations. Interestingly, all the title compounds exhibit semiconducting behaviors: their optical absorption edges calculated from reflectance spectra are in the range of 2.54–2.68 eV; their electrical conductivities measured by using two-probe direct current (DC) method indicate values from 2.06 × 10–9to 4.65 × 10–6S/cm, which are typical for semiconductors and comparable to the reported crystalline hybrid metal halides. The luminescent property studies reveal that only compounds 3and 6exhibit intense emissions both at 77 and 298 K, probably owing to the minimum distortion of the TeCl6octahedra in 3and 6.

Systemic juvenile idiopathic arthritis (SJIA) is a severe childhood arthropathy with features of autoinflammation. Monocytes and macrophages in SJIA have a complex phenotype with both pro‐ and anti‐inflammatory properties that combine features of several well characterized in vitro conditions used to activate macrophages. An important anti‐inflammatory phenotype is expression of CD163, a scavenger receptor that sequesters toxic pro‐inflammatory complexes that is highly expressed in both active SJIA and macrophage activation syndrome (MAS). CD163 is most strongly up‐regulated by IL‐10 (M(IL‐10)), and not by other conditions that reflect features seen in SJIA monocytes such as M(LPS+IC). MicroRNA plays key roles in integrating cellular signals such as those in macrophage polarization, and as such we hypothesize microRNAs regulate macrophage functional responses in SJIA including CD163 expression. We find that 2 microRNAs previously found to be elevated in active SJIA, miR‐125a‐5p and miR‐181c, significantly reduced macrophage CD163 expression through 2 distinct mechanisms. Neither microRNA was elevated in M(IL‐10) with robust CD163 expression, but were instead induced in M(LPS+IC) where they restricted CD163 mRNA expression. Mir‐181 species directly targeted CD163 mRNA for degradation. In contrast, miR‐125a‐5p functions indirectly, as transcriptome analysis of miR‐125a‐5p overexpression identified “cytokine‐cytokine receptor interactions” as the most significantly repressed gene pathway, including decreased IL10RA, required for IL‐10‐mediated CD163 expression. Finally, overexpression of miR‐181c inhibited CD163 anti‐inflammatory responses to hemoglobin or high mobility group box 1 (HMGB1) complexes. Together, these data show that microRNA utilizes multiple mechanisms to integrate well‐characterized polarization phenotypes and regulate macrophage functional properties seen in SJIA.

BackgroundAutosomal recessive mutations in DNAJC12, encoding a cochaperone of HSP70 with hitherto unknown function, were recently described to lead to hyperphenylalaninemia, central monoamine neurotransmitter (dopamine and serotonin) deficiency, dystonia and intellectual disability in six subjects affected by homozygous variants.ObjectivePatients exhibiting hyperphenylalaninemia in whom deficiencies in hepatic phenylalanine hydroxylase and tetrahydrobiopterin cofactor metabolism had been excluded were subsequently analysed for DNAJC12variants.MethodsTo analyse DNAJC12, genomic DNA from peripheral blood (Sanger sequencing), as well as quantitative messenger RNA (Real Time Quantitative Polymerase Chain Reaction (RT-qPCR)) and protein expression (Western blot) from primary skin fibroblasts were performed.ResultsWe describe five additional patients from three unrelated families with homozygosity/compound heterozygosity in DNAJC12with three novel variants: c.85delC/p.Gln29Lysfs*38, c.596G>T/p.*199Leuext*42 and c.214C>T/p.(Arg72*). In contrast to previously reported DNAJC12-deficient patients, all five cases showed a very mild neurological phenotype. In two subjects, cerebrospinal fluid and primary skin fibroblasts were analysed showing similarly low 5-hydroxyindolacetic acid and homovanillic acid concentrations but more reduced expressions of mRNA and DNAJC12 compared with previously described patients. All patients responded to tetrahydrobiopterin challenge by lowering blood phenylalanine levels.ConclusionsDNAJC12 deficiency appears to result in a more heterogeneous neurological phenotype than originally described. While early identification and institution of treatment with tetrahydrobiopterin and neurotransmitter precursors is crucial to ensure optimal neurological outcome in DNAJC12-deficient patients with a severe phenotype, optimal treatment for patients with a milder phenotype remains to be defined.

A hallmark of systemic lupus erythematosus is high titers of circulating autoantibodies. Recently, a novel CD11c+B-cell subset has been identified that is critical for the development of autoimmunity. However, the role of CD11c+B cells in the development of lupus is unclear. Chronic graft-versus-host disease (cGVHD) is a lupus-like syndrome with high autoantibody production. The purpose of this study was to explore the role of CD11c+B cells in the pathogenesis of lupus in cGVHD mice. cGVHD was induced by an intraperitoneal injection of 5 × 107Bm12 splenocytes into B6 mice. Flow cytometry was used to analyze mice splenocytes and human samples. Magnetic beads were used to isolate mice B cells. Gene expression was determined by real-time quantitative polymerase chain reaction (RT-qPCR). Enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies in serum and supernatants. The percentage and absolute number of CD11c+B cells was increased in cGVHD-induced lupus, with elevated levels of antichromatin immunoglobulin (Ig)G and IgG2a in sera. CD11c+plasma cells from cGVHD mice produced large amounts of antichromatin IgG2a upon stimulation. Depletion of CD11c+B cells reduced antichromatin IgG and IgG2a production. T-bet was upregulated in CD11c+B cells. Knockout of T-bet in B cells alleviated cGVHD-induced lupus. Importantly, the percentage of T-bet+CD11c+B cells increased in lupus patients and positively correlated with serum antichromatin levels. T-bet+CD11c+B cells promoted high antichromatin IgG production in the lupus-like disease model cGVHD. In lupus patients, the percentage of T-bet+CD11c+B cells was elevated and positively correlated with antichromatin antibodies. The findings provide potential therapeutic insight into lupus disease treatment.

Cell-penetrating peptides (CPPs), also called “Trojan-Horse” peptides, have been used for facilitating intracellular delivery of numerous diverse cargoes and even nanocarriers. However, the lack of targeting specificity (“wildness” or nonselectivity) of CPP-nanocarriers remains an intractable challenge for many in vivo applications. In this work, we used an intelligent “peptide-gathering mechanical arm” (Int PMA) to curb CPPs’ wildness and enhance the selectivity of R9-liposome-based cargo delivery for tumor targeting. The peptide NGR, serving as a cell-targeting peptide for anchoring, and peptide PLGLAG, serving as a substrate peptide for deanchoring, were embedded in the Int PMA motif. The Int PMA construct was designed to be sensitive to tumor microenvironmental stimuli, including aminopeptidase N (CD13) and matrix metalloproteinases (MMP-2/9). Moreover, Int PMA could be specifically recognized by tumor tissues via CD13-mediated anchoring and released for cell entry by MMP-2/9-mediated deanchoring. To test the Int PMA design, a series of experiments were conducted in vitro and in vivo. Functional conjugates Int PMA-R9-poly(ethylene glycol) (PEG)2000-distearoylphosphatidyl-ethanolamine (DSPE) and R9-PEG2000-DSPE were synthesized by Michael addition reaction and were characterized by thin-layer chromatography and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. The Int PMA-R9-modified doxorubicin-loaded liposomes (Int PMA-R9-Lip-DOX) exhibited a proper particle diameter (approximately 155 nm) with in vitro sustained release characteristics. Cleavage assay showed that Int PMA-R9peptide molecules could be cleaved by MMP-2/9 for completion of deanchoring. Flow cytometry and confocal microscopy studies indicated that Int PMA-R9-Lip-DOX can respond to both endogenous and exogenous stimuli in the presence/absence of excess MMP-2/9 and MMP-2/9 inhibitor (GM6001) and effectively function under competitive receptor-binding conditions. Moreover, Int PMA-R9-Lip-DOX generated more significant subcellular dispersions that were especially evident within endoplasmic reticulum (ER) and Golgi apparatus. Notably, Int PMA-R9-Lip-DOX could induce enhanced apoptosis, during which caspase 3/7 might be activated. In addition, Int PMA-R9-Lip-DOX displayed enhanced in vitro and in vivo antitumor efficacy versus “wild” R9-Lip-DOX. On the basis of investigations at the molecular level, cellular level, and animals’ level, the control of Int PMA was effective and promoted selective delivery of R9-liposome cargo to the target site and reduced nonspecific uptake. This Int PMA-controlled strategy based on aminopeptidase-guided anchoring and protease-triggered deanchoring effectively curbed the wildness of CPPs and bolstered their effectiveness for in vivo delivery of nanotherapeutics. The specific nanocarrier delivery system used here could be adapted using a variety of intelligent designs based on combinations of multifunctional peptides that would specifically and preferentially bind to tumors versus nontumor tissues for tumor-localized accumulation in vivo. Thus, CPPs have a strong advantage for the development of intelligent nanomedicines for targeted tumor therapy.

Core IdeasA standardization‐based method was adopted to quantify the contribution rate.The experiment was specifically designed to isolate the effect of sediment load on detachment rate.The negative contribution of sediment load on detachment rate was almost one‐third of the total.This study aimed at rill erosion of loessial soil. Sediment load changes with downslope distance during rill erosion process, and thus quantifying the potential contribution of sediment load on soil detachment rate is essential to accurately model the rill erosion process. A standardization‐based method was adopted to quantify the contribution for the first time, and the rill flume with a soil‐feeding hopper was specifically designed to insulate the effect of sediment load on detachment rate. Loessial soil was quantitatively fed into rill flow to produce different sediment loads. Seven flow discharges were combined with six slopes. Soil detachment rate was measured for each combination under five sediment loads (10, 25, 50, 75, and 90% of the sediment transport capacity, respectively). The results showed that soil detachment rate by sediment‐laden rill flow decreased linearly with the increase in sediment load. Stream power is the best hydrodynamic parameter in relation to the detachment rate under different sediment loads compared with shear stress and unit stream power. The comprehensive response relationship of soil detachment rate to sediment load and stream power is a binary linear equation (R2= 0.9482). The contribution rate of sediment load to soil detachment rate is 30.43% and that of stream power is 64.39%. The negative effect of sediment load on soil detachment rate accounts for almost one‐third of the total contribution. It is important to draw sediment load as a negative factor into process‐based rill erosion model. This study can provide a feasible way for researchers to quantify the contribution rate of factors and can help to understand rill erosion process sufficiently.

Long non-coding RNAs (lncRNAs) have emerged as key epigenetic regulators that govern gene expression and influence multiple biological processes. Accumulating evidence demonstrates that lncRNAs have critical roles in immune cell development and function. In this Review, the molecular mechanisms of gene expression regulation by lncRNAs are described and current knowledge of the role of lncRNAs in immune regulation and inflammation are presented, highlighting strategies for defining the roles of lncRNAs in the pathogenesis of multiple rheumatic diseases. Finally, research progress in understanding the role of lncRNAs in rheumatic diseases is discussed.

This study aimed to clarify the characteristics of intestinal microbiota in children with hand, foot, and mouth disease (HFMD) under 3 years old. Fresh feces were collected from 54 children with HFMD and 30 healthy children. All of them were <3 years old. Sequencing of the 16S rDNA amplicons was performed. Between the 2 groups, the richness, diversity, and structure of the intestinal microbiota were analyzed by α-diversity and β-diversity. Linear discriminant analysis and LEfSe analyses were used to compare different bacterial classifications. The sex and age of the children in the 2 groups were not statistically significant (P = .92 and P = .98, respectively). Compared to healthy children, the Shannon index, Ace index, and Chao index were lower in children with HFMD (P = .027, P = .012, and P = .012, respectively). Based on the weighted or unweighted UniFrac distance analysis, the structure of the intestinal microbiota in HFMD was also significantly changed (P = .002 and P < .001, respectively). Linear discriminant analysis and LEfSe analysis showed that the changes of key bacteria were manifested as a decrease in Prevotellaand Clostridium_XIVa (P < .001 and P < .001, respectively), while Escherichiaand Bifidobacteriumincreased (P = .025 and P = .001, respectively). Children with HFMD under 3 years of age have intestinal microbiota disorder and show a decrease in diversity and richness. The decrease in the abundance of Prevotellaand Clostridium, which can produce short-chain fatty acids, is also one of the characteristics of the change. These results can offer a theoretical foundation for the pathogenesis and microecological treatment of HFMD in infants.

As a potential alternative to the prevailing lithium ion batteries, the application of sodium (Na) ion batteries (NIBs) in renewable energy and smart grid have revitalized research interest for large-scale energy storage. One of the roadblocks hindering their future commercialization is the development of suitable anode materials. Herein, we present the large-scale preparation of highly uniform iron sulfide (Fe1−xS) nanostructures by a cost-effective and versatile one-step sulfurization strategy. Impressively, as a high-rate and viable sodium-ion anode, the as-prepared Fe1−xS nanostructure manifests appealing electrochemical performance (a high discharge capacity of 563mAhg−1over 200 cycles at a current density of 100mAg−1and outstanding cycling stability even at high rate of 10Ag−1up to 2000 cycles). Moreover, the proven pseudocapacitance contribution interprets the unprecedented rate capability. Meanwhile, the sodium storage mechanism in the as-prepared samples has also been investigated by using the in-situ X-ray diffraction techniques. Remarkably, a full cell based on Na0.6Co0.1Mn0.9O2cathode and Fe1−xS anode deliver high discharge capacity (393mAhg−1) and superior cycling stability.

TLR7/9 signals are capable of mounting massive interferon (IFN) response in plasmacytoid dendritic cells (pDCs) immediately after viral infection, yet the involvement of epigenetic regulation in this process has not been documented. Here, we report that zinc finger CXXC family epigenetic regulator CXXC5 is highly expressed in pDCs, where it plays a crucial role in TLR7/9- and virus-induced IFN response. Notably, genetic ablation of CXXC5 resulted in aberrant methylation of the CpG-containing island (CGI) within the Irf7 gene and impaired IRF7 expression in steady-state pDCs. Mechanistically, CXXC5 is responsible for the recruitment of DNA demethylase Tet2 to maintain the hypomethylation of a subset of CGIs, a process coincident with active histone modifications and constitutive transcription of these CGI-containing genes. Consequently, CXXC5-deficient mice had compromised early IFN response and became highly vulnerable to infection by herpes simplex virus and vesicular stomatitis virus. Together, our results identify CXXC5 as a novel epigenetic regulator for pDC-mediated antiviral response.

Four new azaphilones, penicilones A–D (1–4), were isolated from the mangrove rhizosphere soil-derived fungus Penicillium janthinellumHK1-6. Their planar structures and absolute configurations were determined by extensive analysis of NMR spectroscopic data, ECD spectra, the modified Mosher’s method, and chemical conversions. Interestingly, 1and 2had the opposite configuration at C-7 compared to the closely related chloro analogues 3and 4. Ester hydrolysis of 2and 4afforded their parental azaphilones, named penicilones E (5) and F (6). Compounds 1–6were evaluated for their antibacterial activities in vitro. Penicilones B–D (2–4) showed potent anti-MRSA (Staphylococcus aureusATCC 43300, ATCC 33591) activities with MIC values ranging from 3.13 to 6.25 μg/mL.

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with a strong genetic component characterized by autoantibody production and a type I interferon signature. Here we report a missense variant (g.74779296G>A; p.Arg90His) in NCF1, encoding the p47phoxsubunit of the phagocyte NADPH oxidase (NOX2), as the putative underlying causal variant that drives a strong SLE-associated signal detected by the Immunochip in the GTF2IRD1–GTF2I region at 7q11.23 with a complex genomic structure. We show that the p.Arg90His substitution, which is reported to cause reduced reactive oxygen species (ROS) production, predisposes to SLE (odds ratio (OR) = 3.47 in Asians (Pmeta= 3.1 × 10−104), OR = 2.61 in European Americans, OR = 2.02 in African Americans) and other autoimmune diseases, including primary Sjögren's syndrome (OR = 2.45 in Chinese, OR = 2.35 in European Americans) and rheumatoid arthritis (OR = 1.65 in Koreans). Additionally, decreased and increased copy numbers of NCF1 predispose to and protect against SLE, respectively. Our data highlight the pathogenic role of reduced NOX2-derived ROS levels in autoimmune diseases.

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.

Large-scale vegetation restoration can reduce local watershed water yield, limit vegetation establishment and subsequent growth, and influence regional ecosystem functions. Clipping management by reducing aboveground parts of grassland was gradually recommended and adopted in Grain-for-Green project management to offset these additional issues. Thus, scientific evaluation of the effectiveness of clipping management on infiltration and runoff processes is necessary for maintaining the stability of the surface water system and the sustainability of vegetation restoration in semi-arid regions. A field simulated rainfall experiment was conducted with four managed clipping grasslands (mainly bunge needlegrassand Stipa grandis), including no clipping, light clipping, heavy clipping, and complete clipping under three slope gradients (10, 20, and 30°) and three rainfall intensities (60, 90, and 120 mm/h) to explore the mechanism of runoff and infiltration responses to clipping using structural equation modeling and variation partitioning based on an SCS-CN model. The results showed the runoff coefficient of the light clipping, heavy clipping, and complete clipping plots were 1.33, 2.22, and 4.22 times that of the no clipping plot. The light clipping, heavy clipping, and complete clipping plots decreased the infiltration coefficients by 0%, 5%, and 26% relative to the no clipping plot. Rainfall intensity dominated runoff and infiltration amounts, and clipping intensity's total effect was stronger than slope gradient. Clipping intensity and slope gradient were more influential on runoff with increasing rainfall intensity. The mutual inhibition effect was between clipping intensity and slope gradient on runoff. In order to maintain the sustainability of restoration, a 25–50% vegetation coverage after clipping maximizes the benefits of increasing runoff and maintaining enough soil water supply that prevents possible soil drought. We propose that future vegetation restoration policies should evaluate the appropriate clipping intensity; meanwhile, local physiographic and climate conditions should be considered. These findings may offer guidance for the development of measures for runoff regulation and ecosystem functions of the watershed during vegetation restoration on the northern Loess Plateau.

Objective: There is an urgent need to identify novel biomarkers of LN to reflect renal histological changes. This study aims to investigate urinary G3BP levels in LN patients and their association with renal disease activity both clinically and pathologically. Methods: This is a cross-sectional study. A total of 119 lupus nephritis patients were recruited. Thirty patients with chronic kidney diseases (CKD) and 27 healthy volunteers were also recruited as controls. Urinary G3BP was tested by ELISA. Renal histopathology was reviewed by an experienced renal pathologist. Other clinical variables were collected through chart review. Results: The levels of uG3BP were significantly increased in active LN patients compared to those in inactive LN (p&lt;0.001), CKD patients (p=0.01), and healthy controls (p&lt;0.001). ROC analysis indicated a good discrimination ability of uG3BP to differentiate active LN from CKD patients (AUC=0.7), inactive LN (AUC=0.76), or healthy controls (AUC=0.87). uG3BP was positively correlated with SLEDAI (ρ=0.352, p&lt;0.001), rSLEDAI (ρ=0.302, p&lt;0.001), and SLICC RAS (ρ=0.465, p&lt;0.001), indicating a role as a biomarker of disease activity. It also correlated with clinical parameters, including 24-h urine protein, ESR, and serum C3 levels. In patients with 24-h urine protein > 3.0 g/24h, uG3BP levels were higher in proliferative LN than in membranous LN (p=0.04). They could discriminate the two pathogenic types of LN (AUC=0.72), and they also positively correlated with AI (ρ=0.389, p=0.008) and scores of hyaline deposits (ρ=0.418, p=0.006). While in patients with 24-h urine protein ≤ 3.0 g/24h, uG3BP levels were not significantly different between proliferative and membranous LN, and there was no apparent relationship between uG3BP levels with AI or with scores of hyaline deposits, but they correlated positively with scores of cellular/fibrocellular crescents (ρ=0.328, p=0.04). Conclusion: uG3BP is a non-invasive biomarker for clinically and histologically reflecting disease activity. It is associated with active histological changes and can be used as a surrogate biomarker when the renal biopsy is impractical.