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Abstract Background Nephrotic syndrome (NPHS), characterized by proteinuria, hypoalbuminemia, and edema, can be caused by genetic variations. TBC1D8B was recently discovered as a novel disease-causing gene for X-linked NPHS. With only a few reported cases, the clinical manifestations associated with variants of this gene need to be further examined. Methods We recruited a newborn with NPHS complicated by acute kidney injury (AKI) and his parents and tested the potential genetic cause of the disease through trio-whole exome sequencing and Sanger sequencing. Western blotting (WB) was performed using a mutant plasmid to evaluate mutant protein expression levels. Since the TBC1D8B protein interacts with RAB proteins to catalyze the GTPase hydrolysis process, immunofluorescence (IF) can be used to verify the interaction between the TBC1D8B mutant protein and RAB11A/RAB11B, and thus to confirm its effect on the endocytosis and vesicle recycling functions of RAB proteins within the cell. Results The child, at 1 month, showed severe edema and proteinuria and unexplained coma with epilepsy. Ultrasound examination revealed multiple organ enlargement, and MRI showed nonspecific high diffusion-weighted imaging signal characteristics in the splenium of the corpus callosum. Hematoxylin and eosin staining showed diffuse inflammatory cell infiltration in the renal interstitium and multifocal renal tubule lumen expansion. Diffuse fusion of podocyte foot processes was observed under electron microscopy, indicating glomerular podocyte lesions. Genetic testing revealed a maternally inherited novel hemizygous variant, NM_017752: c.628 A > T, p.Lys210Ter, in TBC1D8B. In vitro functional experiments showed that this variant may lead to TBC1D8B protein degradation. IF results showed disrupted interaction with RAB11A/RAB11B, that then affects the biological function of RAB proteins in the process of cell intimal vesicle formation and intracellular transport. Conclusion This study will enrich the mutational and phenotypic spectra of TBC1D8B and demonstrate the potential of this gene variants to cause early-onset NPHS leading to severe kidney disease.

Abstract Background It is challenging to correctly identify and diagnose breast nonmass lesions. This study aimed to explore the multimodal ultrasound features associated with malignant breast nonmass lesions (NMLs), and evaluate their combined diagnostic performance. Methods This retrospective analysis was conducted on 573 breast NMLs, including 309 were benign and 264 were malignant, their multimodal ultrasound features (B-mode, color Doppler and strain elastography) were assessed by two experienced radiologists. Univariate and multivariate logistic regression analysises were used to explore multimodal ultrasound features associated with malignancy, and a nomogram was developed. Diagnostic performance and clinical utility were evaluated and validated by the receiver operating characteristic (ROC) curve, calibration curve and decision curve in the training and validation cohorts. Results Multimodal ultrasound features including linear (odds ratio [OR] = 4.69) or segmental distribution (OR = 7.67), posterior shadowing (OR = 3.14), calcification (OR = 7.40), hypovascularity (OR = 0.38), elasticity scored 4 (OR = 7.00) and 5 (OR = 15.77) were independent factors associated with malignant breast NMLs. The nomogram based on these features exhibited diagnostic performance in the training and validation cohorts were comparable to that of experienced radiologists, with superior specificity (89.4%, 89.5% vs. 81.2%) and positive predictive value (PPV) (89.2%, 90.4% vs. 82.4%). The nomogram also demonstrated good calibration in both training and validation cohorts (all P > 0.05). Decision curve analysis indicated that interventions guided by the nomogram would be beneficial across a wide range of threshold probabilities (0.05-1 in the training cohort and 0.05–0.93 in the validation cohort). Conclusions The combined use of linear or segmental distribution, posterior shadowing, calcification, hypervascularity and high elasticity score, displayed as a nomogram, demonstrated satisfied diagnostic performance for malignant breast NMLs, which may contribute to the imaging interpretation and clinical management of tumors.

Abstract Background Hereditary angioedema (HAE) is a rare autosomal dominant genetic disease characterized by recurrent edema and a potentially fatal risk. Despite its severity, there is a notable lack of effective methods for predicting and preventing HAE attacks. This study aims to thoroughly investigate the underlying pathological mechanisms of HAE and identify potential biomarkers that could aid in its prediction and prevention. Results In our investigation, we have discovered a novel pathogenic variant of the SERPING1 gene, specifically c.708T > G, in a Han family affected by HAE. Our observations indicate that this variant leads to an increase in the accumulation of C1-INH within the endoplasmic reticulum (ER), resulting in the upregulation of GRP75 protein expression. This cascade of events resulted in Ca2+ overload, disruption of mitochondrial structure and function, and eventually triggered apoptosis. Using siRNA to knock down GRP75 mitigates cellular calcium overload and mitochondrial damage induced by the SERPING1 mutation. Conclusion Based on our findings, we propose that the detection of intracellular Ca2+ concentration could serve as a valuable biomarker for predicting acute attacks of HAE in patients. This discovery holds significant implications for the development of more targeted and effective strategies in the management of HAE.

Abstract Pathological myopia (PM) is one of the leading causes of blindness, especially in Asia. To identify the genetic risk factors of PM, a two‐stage genome‐wide association study (GWAS) and replication analysis in East Asian populations is conducted. The analysis identified LILRB2 in 19q13.42 as a new candidate locus for PM. The increased protein expression of LILRB2/Pirb (mouse orthologous protein) in PM patients and myopia mouse models is validated. It is further revealed that the increase in LILRB2/Pirb promoted fatty acid synthesis and lipid accumulation, leading to the destruction of choroidal function and the development of PM. This study revealed the association between LILRB2 and PM, uncovering the molecular mechanism of lipid metabolism disorders leading to the pathogenesis of PM due to LILRB2 upregulation.

Abstract Background Automated Breast Ultrasound (AB US) has shown good application value and prospects in breast disease screening and diagnosis. The aim of the study was to explore the ability of AB US to detect and diagnose mammographically Breast Imaging Reporting and Data System (BI-RADS) category 4 microcalcifications. Methods 575 pathologically confirmed mammographically BI-RADS category 4 microcalcifications from January 2017 to June 2021 were included. All patients also completed AB US examinations. Based on the final pathological results, analyzed and summarized the AB US image features, and compared the evaluation results with mammography, to explore the detection and diagnostic ability of AB US for these suspicious microcalcifications. Results 250 were finally confirmed as malignant and 325 were benign. Mammographic findings including microcalcifications morphology (61/80 with amorphous, coarse heterogeneous and fine pleomorphic, 13/14 with fine-linear or branching), calcification distribution (189/346 with grouped, 40/67 with linear and segmental), associated features (70/96 with asymmetric shadow), higher BI-RADS category with 4B (88/120) and 4 C (73/38) showed higher incidence in malignant lesions, and were the independent factors associated with malignant microcalcifications. 477 (477/575, 83.0%) microcalcifications were detected by AB US, including 223 malignant and 254 benign, with a significantly higher detection rate for malignant lesions (x 2 = 12.20, P

In order to improve the wear resistance of Ti-25Nb-3Zr-2Sn-3Mo(TLM) titanium alloy, the composite coating on surface of alloy was prepared by surface mechanical composite strengthening(SMCS) process. The microstructure, micromechanical properties and tribological properties of the composite coating were studied. Results showed that TiN/Sn composite coatings could be successfully prepared on the alloy surface using surface mechanical composite strengthening technology. As the Sn content increased, the thickness and roughness of the composite coating continued to increase, and the thickness of 10%～40% Sn coatings was 9.08, 14.05, 18.33 and 23.55 μm, respectively. Additionally, the surface hardness of 10%～40% Sn coatings was 590, 529, 465 and 400 HV, respectively, which was higher than that of the matrix hardness(～230 HV). Furthermore, the wear amounts of the composite coating decreased first and then increased with the increase of Sn content, and the 20% Sn coating had the lowest wear amount. In the dry wear test, the wear mechanism of original sample was mainly adhesive wear and accompanied by abrasive wear, while the wear mechanism of the composite reinforced sample was abrasive wear, adhesive wear and accompanied by oxidation wear.

Abstract Dexmedetomidine (Dex) has been used in surgery to improve patients' postoperative cognitive function. However, the role of Dex in stress-induced anxiety-like behaviors and cognitive impairment is still unclear. In this study, we tested the role of Dex in anxiety-like behavior and cognitive impairment induced by acute restrictive stress and analyzed the alterations of the intestinal flora to explore the possible mechanism. Behavioral and cognitive tests, including open field test, elevated plus-maze test, novel object recognition test, and Barnes maze test, were performed. Intestinal gut Microbe 16S rRNA sequencing was analyzed. We found that intraperitoneal injection of Dex significantly improved acute restrictive stress-induced anxiety-like behavior, recognition, and memory impairment. After habituation in the environment, mice (male, 8 weeks, 18–23 g) were randomly divided into a control group (control, N = 10), dexmedetomidine group (Dex, N = 10), AS with normal saline group (AS + NS, N = 10) and AS with dexmedetomidine group (AS + Dex, N = 10). By the analysis of intestinal flora, we found that acute stress caused intestinal flora disorder in mice. Dex intervention changed the composition of the intestinal flora of acute stress mice, stabilized the ecology of the intestinal flora, and significantly increased the levels of Blautia (A genus of anaerobic bacteria) and Coprobacillus. These findings suggest that Dex attenuates acute stress-impaired learning and memory in mice by maintaining the homeostasis of intestinal flora.

The interaction between endoplasmic reticulum (ER) and mitochondria has been shown to play a key role in hepatic steatosis during chronic obesity. β-nicotinamide mononucleotide (NMN) has been reported to regulate obesity, however, its molecular mechanism at the subcellular level remains unclear. Here, NMN improved liver steatosis and insulin resistance in chronic high-fat diet (HFD) mice. RNA-seq showed that compared with the liver of HFD mice, NMN intervention enhanced fat digestion and absorption and stimulated the cholesterol metabolism signaling pathways, while impaired insulin resistance and the fatty acid biosynthesis signaling pathways. Mechanistically, NMN ameliorated mitochondrial dysfunction and ER oxidative stress in the liver of HFD mice by increasing hepatic nicotinamide adenine dinucleotide (NAD+) (P < 0.01) levels. This effect increased the contact sites (mitochondria-associated membranes [MAMs]) between ER and mitochondria, thereby promoting intracellular ATP (P < 0.05) production and mitigating lipid metabolic disturbances in the liver of HFD mice. Taken together, this study provided a theoretical basis for restoring metabolic dynamic equilibrium in the liver of HFD mice by increasing MAMs via the nutritional strategy of NMN supplementation.

Abstract In this research, a modeling approach of rainfall generator coupled with high resolution rainfall products were proposed to generate designed rainfall events under multiple spatial and temporal distributions, which was then employed to analyze the impacts of spatial and temporal rainfall heterogeneities on peak runoff for watersheds. Three scenarios were developed under multiple degrees of impermeable underlying surface areas within an urban watershed in south China. Detailed runoff processes were analyzed through the adoption of a distributed hydrological model (GSSHA). A covariance analysis method combined with rainfall spatio‐temporal heterogeneity characteristic were used to quantify heterogeneity effects on peak runoff. Results indicated that coupling short period (2008–2016) remotely rainfall data and RainyDay results could successfully reproduce designed rainfall events, spatio‐temporal heterogeneity of rainfall contributed significantly to the peak runoff, which was greater than those by rainfall duration and capacity, and the increase in impermeable underlying surface enhanced the complexities of the effects. Over each rainfall duration with increasing rainfall return period, the indicator of rainfall peak coefficient (RWD) would decrease and then increase. Regarding the total rainfall center (tg), 25 mm/h threshold rainfall spatial coverage (A25) decreased with increasing imperviousness, 1‐h maximum rainfall (Rmax) surged with increasing imperviousness at rainfall duration of 2 and 24 h. Innovations of this research lied in: combination of a rainfall generator model based on a stochastic storm transposition technique and remote‐sensing rainfall data to generate designed rainfall events, a rainfall spatial and temporal heterogeneities index system was developed to reveal how the changing characteristics of rainfall distribution and the impacts on peak runoff, and in‐depth analysis of the impacts on runoff peak under multiple urban development scenarios for increasing capability in flood control/prevention.

Abstract Neurogenins are proneural transcription factors required to specify neuronal identity. Their overexpression in human pluripotent stem cells rapidly produces cortical-like neurons with spiking activity and, because of this, they have been widely adopted for human neuron disease models. However, we do not fully understand the key downstream regulatory effectors responsible for driving neural differentiation. Here, using inducible expression of NEUROG1 and NEUROG2, we identify transcription factors (TFs) required for directed neuronal differentiation by combining expression and chromatin accessibility analyses with a pooled in vitro CRISPR-Cas9 screen targeting all ~1900 TFs in the human genome. The loss of one of these essential TFs (ZBTB18) yields few MAP2-positive neurons. Differentiated ZBTB18-null cells have radically altered gene expression, leading to cytoskeletal defects and stunted neurites and spines. In addition to identifying key downstream TFs for neuronal differentiation, our work develops an integrative multi-omics and TFome-wide perturbation platform to rapidly characterize essential TFs for the differentiation of any human cell type.

This research introduces an innovative construction method based on magnesia expansive agent concrete for the seamless construction of hundred-meter scale super-length raft structures, corroborated by the on-site test. The basic principle of this construction method is to use the pre compression stress generated by magnesia expansive agent to offset temperature and shrinkage stress. A temperature-strain monitoring system was employed to gather data, affirming the technique’s applicability and safety. Through the examination of temperature and strain dispersion trends in super-length raft structure, recommendations for the configuration of temperature-strain sensors have been put forth. Through the scrutiny of the temporal evolution pattern of temperature, the specific temporal and spatial coordinates that warrant particular vigilance during the surveillance of the raft’s inner-surface temperature difference were identified. Upon evaluating the correlation between strain dispersion and strain-temperature differential in the raft’s thickness dimension, a novel temperature control index (the bottom-surface temperature difference) was introduced. The threshold for this metric was established at 30°C, derived from empirical test outcomes conducted on-site. Furthermore, the critical regions for monitoring the bottom-surface temperature difference were specified.

Abstract Background Treatment options for pregnant women with immune thrombocytopenia (ITP) who do not respond to first-line treatment are limited. Few studies have reported the use of recombinant human thrombopoietin (rhTPO) for this subset of patients. Aims To investigate the efficacy and safety of rhTPO in ITP during pregnancy and determine obstetric outcomes and predictors of treatment response. Methods From July 2013 to October 2022, the data of 81 pregnant women with ITP and a platelet count 0.05, both). Compared with controls, rhTPO patients had higher platelet counts (median [interquartile range]: 42 [21.5–67.5] vs. 25 [19–29] × 109/L, P = 0.002), lower bleeding rate (6.1% vs. 25%, P = 0.027), and lower platelet transfusion rate before delivery (57.6% vs. 97.9%, P 0.05). No liver or renal function impairment or thrombosis cases were observed in the rhTPO group. GEE analysis revealed that the baseline mean platelet volume (MPV) (odds ratio [OR]: 0.522, P = 0.002) and platelet-to-lymphocyte ratio (PLR) (OR: 1.214, P = 0.025) were predictors of response to rhTPO treatment. Conclusion rhTPO may be an effective and safe treatment option for pregnancies with ITP that do not respond to first-line treatment; it may have slightly prolonged the gestational age of delivery. Patients with a low baseline MPV and high baseline PLR may be more responsive to rhTPO treatment. The present study serves as a foundation for future research.

The construction industry plays a pivotal role in China’s achievement of its “dual carbon” goals. This study conducts a decomposition analysis of the carbon emissions from the construction industry (CECI) at both national and provincial levels for the period 2010–2020 and employs the ARIMA model to predict the short-term peak trends at the provincial level. The findings are as follows. (1) Inner Mongolia, Shandong, Sichuan, and Chongqing exhibit an N-shaped trend in CECI, while the northeast region shows an inverted U-shaped trend. (2) Labor productivity and energy intensity are identified as the largest and smallest drivers of national CECI growth, respectively, with the driving force of the study’s identified factors fluctuating between 1% and 60%. (3) Energy intensity significantly contributes to the growth of CECI in Tianjin and Zhejiang, while it aids in reducing CECI in western provinces. The “rebound effect” of building energy efficiency is particularly pronounced in provinces with strong resource endowments, such as Ningxia. (4) Between 2021 and 2025, CECI is predicted to decrease in the northern and economically developed provinces, while it is expected to increase in central and western provinces, with Heilongjiang, Shandong, Guangdong, Shanghai, and Shaanxi potentially reaching their peaks within the forecast period. The paper concludes with several recommendations.

Interprovincial disparities in carbon emissions from the construction industry (CECI) are an important challenge for future emissions reductions. Based on the CECI data of 30 provinces in China from 2010 to 2020, the interprovincial equity and decoupling of CECI were examined in this study. The conclusions are as follows: (1): The main CECI growth regions were the eastern Bohai Rim region and the Pearl River Delta region. Heilongjiang basically achieved a CECI carbon peak in 2016. (2) The three northeastern provinces and western provinces were the main high–high and low–low aggregation areas, respectively. The greatest degree of inequality was found in the western provinces. The inequality between the eastern and western areas was the largest, while the inequality between the central and western areas was the smallest. The inequality in CECI in the north–south region decreased year by year. (3) The decoupling status of Shandong and some western provinces has significantly worsened, while the decoupling status of Sichuan, Yunnan, and some eastern developed provinces has been improving. These conclusions will contribute to the improvement of regional emission reduction strategies.

Abstract Spaceborne interferometric synthetic aperture radar (InSAR) technology is an effective method to obtain digital elevation model (DEM) data. The bistatic InSAR configuration of the inclined‐geosynchronous (InGEO) transmitter with low earth orbit (LEO) receivers (InGEO‐LEO) is a novel InSAR system to acquire terrain information. This novel system is characterised with high resolution, wide swath and timeliness, but the Newton iterative method is time‐consuming to solve the bistatic InSAR equations for fast DEM generation. For the conventional LEO bistatic InSAR system, the closed‐form solution is an effective method to improve the efficiency of solving InSAR equations, which is invalid in the InGEO‐LEO InSAR system because of the significant geometry difference caused by the orbits of InGEO transmitter and LEO receivers. To address this issue, we analyse the bistatic InGEO‐LEO geometry in detail and exploit the bistatic InSAR equations to propose an approximate closed‐form solution (ACS) for the novel system. Compared with the general Newton iterative method, the ACS significantly improves the efficiency of geolocation for the bistatic InGEO‐LEO InSAR system with high precision. Simulation experiments are carried out to verify the effectiveness and superiority of ACS.

Abstract Background Currently, the development of breast cancer immunotherapy based on the PD-1/PD-L1 pathway is relatively slow, and the specific mechanism affecting the immunotherapy efficacy in breast cancer is still unclear. Methods Weighted correlation network analysis (WGCNA) and the negative matrix factorization (NMF) were used to distinguish subtypes related to the PD-1/PD-L1 pathway in breast cancer. Then univariate Cox, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression were used to construct the prognostic signature. A nomogram was established based on the signature. The relationship between the signature gene IFNG and breast cancer tumor microenvironment was analyzed. Results Four PD-1/PD-L1 pathway-related subtypes were distinguished. A prognostic signature related to PD-1/PD-L1 pathway typing was constructed to evaluate breast cancer’s clinical characteristics and tumor microenvironment. The nomogram based on the RiskScore could be used to accurately predict breast cancer patients’ 1-year, 3-year, and 5-year survival probability. The expression of IFNG was positively correlated with CD8+ T cell infiltration in the breast cancer tumor microenvironment. Conclusion A prognostic signature is constructed based on the PD-1/PD-L1 pathway typing in breast cancer, which can guide the precise treatment of breast cancer. The signature gene IFNG is positively related to CD8+ T cell infiltration in breast cancer.

Dynamic regulation of cell-extracellular matrix (ECM)-material interactions is crucial for various biomedical applications. In this study, a light-activated molecular switch for the modulation of cell attachment/detachment behaviors was established on monolayer graphene (Gr)/n-type Silicon substrates (Gr/Si). Initiated by light illumination at the Gr/Si interface, pre-adsorbed proteins (bovine serum albumin, ECM proteins collagen-1, and fibronectin) underwent protonation to achieve negative charge transfer to Gr films (n-doping) through π-π interactions. This n-doping process stimulated the conformational switches of ECM proteins. The structural alterations in these ECM interactors significantly reduced the specificity of the cell surface receptor-ligand interaction (e.g., integrin recognition), leading to dynamic regulation of cell adhesion and eventual cell detachment. RNA-sequencing results revealed that the detached bone marrow mesenchymal stromal cell sheets from the Gr/Si system manifested regulated immunoregulatory properties and enhanced osteogenic differentiation, implying their potential application in bone tissue regeneration. This work not only provides a fast and feasible method for controllable cells/cell sheets harvesting but also gives new insights into the understanding of cell-ECM-material communications.

The drive for continuous innovation in large-scale infrastructure necessitates advancements in techniques, addressing the challenges of constructing super-length concrete structures. This study investigated the emerging shift from traditional united expanding agent (UEA) to magnesia expansive agent (MEA) in conjunction with expansive strengthening bands (ESBs), marking a pivotal transition in ensuring monolithic integrity. Despite a decade of exploration, MEA–ESB implementation in real-world projects remains underdocumented, with scholarly focus primarily confined to material characterization. This research integrated empirical on-site tests of MEA–ESB with high-fidelity numerical simulations in ABAQUS. The finite element model (FEM) validation against actual test data underscored the precision of our modeling, capturing the complex thermomechanical behavior of the system. We introduced a sophisticated parametric analysis framework, elucidating the influence of critical parameters like the ESB-to-raft-width ratio and MEA concrete expansion rates. This granular understanding facilitated the fine-tuning of design parameters, advancing the practical application of MEA methodologies. A groundbreaking contribution entailed the formulation of predictive models for early-stage cracking, anchored in the guidelines of the ACI Committee 207 and refined through extensive parametric exploration. These formulae empower engineers to anticipate and mitigate cracking risks during the design phase, thereby enhancing project safety and efficiency. Notably, this study identified limitations in current prediction models, highlighting the need for future research to incorporate comprehensive lifecycle considerations, including hydration heat effects and time-dependent mechanical property evolution.

Summary: Background: Genomic alterations in DNA damage response (DDR) genes are common in metastatic castration-resistant prostate cancer (mCRPC). Understanding how these genomic events impact prognosis and/or treatment response is vital for optimising clinical outcomes. Methods: Targeted sequencing was performed on 407 plasma samples from 375 men with mCRPC. Using the CLIA-certified PredicineCARE™ cell-free DNA (cfDNA) assay, pathogenic alterations in 152 key genes (including 27 DDR-related genes) were assessed, as was the presence and mechanisms of biallelic loss in BRCA2. Findings: At least one DDR alteration was present in 34.5% (129/375) of patients (including monoallelic alterations). The most frequently altered DDR genes were BRCA2 (19%), ATM (13%), FANCA (5%), CHEK2 (5%) and BRCA1 (3%). Patients with BRCA alterations, especially BRCA2, had significantly worse progression-free survival (PFS) (Hazard ratio (HR) 3.3 [95% CI 1.9–6.0]; Cox regression p

Wenzhou has improved its environmental quality because of comprehensive environmental remediation; nevertheless, the semen quality of infertile males remains unclear. This study determined whether better environmental quality improved semen quality in this region. We recorded semen quality data from 22 962 infertile males from January 2014 to November 2019 at the Center for Reproductive Health of The First Affiliated Hospital of Wenzhou Medical University (Wenzhou, China). Patients were predominantly 30–35 years old (33.1%) and workers (82.0%), with high school education or lower (77.6%); more than a half of the patients (52.6%) were Wenzhou household registration; and most patients (77.5%) had abnormal semen quality. Patients who were older than 40 years and workers, and those with Wenzhou household registration, had significantly worse semen quality (all P < 0.05). From 2014 to 2019, progressive sperm motility, total sperm motility, and semen volume showed increasing linear trends in all patients (P = 0.021, 0.030, and 0.005, respectively), yet normal sperm morphology showed a linearly decreasing trend (P = 0.046). Sensitivity analyses for subgroups yielded similar results. In conclusion, the improvement of environmental quality and better function of the accessory glands are associated with progressive sperm motility, total sperm motility, and semen volume. Normal sperm morphology is influenced by occupational exposures and personal lifestyle and does not improve with environmental quality.

ABSTRACT Ectomycorrhizal fungi play an irreplaceable role in phosphorus cycling. However, ectomycorrhizal fungi have a limited ability to dissolve chelated inorganic phosphorus, which is the main component of soil phosphorus. Endofungal bacteria in ectomycorrhizal fruiting bodies are always closely related to the ecological function of ectomycorrhizal fungi. In this study, we explore endofungal bacteria in the fruiting body of Tylopilus neofelleus and their function during the absorption of chelated inorganic phosphorus by host pine through the ectomycorrhizal system. The results showed that the endofungal bacterial microbiota in the fruiting body of T. neofelleus might be related to the dissolution of chelated inorganic phosphorus in soil. The soluble phosphorus content in the combined system of T. neofelleus and endofungal bacteria Bacillus sp. strain B5 was five times higher than the sum of T. neofelleus-only treatment and Bacillus sp. strain B5-only treatment in the dissolution experiment of chelated inorganic phosphorus. The results showed that T. neofelleus not only promoted the proliferation of Bacillus sp. strain B5 in the combined system but also improved the expression of genes related to organic acid metabolism, as assesed by transcriptomic analysis. Lactic acid content was five times higher in the combined system than the sum of T. neofelleus-only treatment and Bacillus sp. strain B5-only treatment. Two essential genes related to lactate metabolism of Bacillus sp. strain B5, gapA and pckA, were significantly upregulated. Finally, in a pot experiment, we verified that T. neofelleus and Bacillus sp. strain B5 could synergistically promote the absorption of chelated inorganic phosphorus by Pinus sylvestris in a ternary symbiotic system. IMPORTANCE Ectomycorrhizal fungi (ECMF) have a limited ability to dissolve chelated inorganic phosphorus, which is the main component of soil phosphorus. In the natural environment, the extraradical hyphae of ECMF alone may not satisfy the phosphorus demand of the plant ectomycorrhizal system. In this study, our results innovatively show that the ectomycorrhizal system might be a ternary symbiont in which ectomycorrhizal fungi might recruit endofungal bacteria that could synergistically promote the mineralization of chelated inorganic phosphorus, which ultimately promotes plant phosphorus absorption by the ectomycorrhizal system.

Summary: The global prevalence and burden of musculoskeletal (MSK) disorders are immense. Advancements in next-generation sequencing (NGS) have generated vast amounts of data, accelerating the research of pathological mechanisms and the development of therapeutic approaches for MSK disorders. However, scattered datasets across various repositories complicate uniform analysis and comparison. Here, we introduce MSdb, a database for visualization and integrated analysis of next-generation sequencing data from human musculoskeletal system, along with manually curated patient phenotype data. MSdb provides various types of analysis, including sample-level browsing of metadata information, gene/miRNA expression, and single-cell RNA-seq dataset. In addition, MSdb also allows integrated analysis for cross-samples and cross-omics analysis, including customized differentially expressed gene/microRNA analysis, microRNA-gene network, scRNA-seq cross-sample/disease integration, and gene regulatory network analysis. Overall, systematic categorizing, standardized processing, and freely accessible knowledge features MSdb a valuable resource for MSK research community.

An inorganic–organic hybrid Eu–W-implanted tartrate-connected selenotungstate tetramer {[Eu4(H2O)12W6O12(tar)2][B-α-SeW9O33]4}16− (1a, H4tar = tartaric acid) was successfully obtained by introducing the flexible multidentate tartrate ligand into the Se-templated lacunary polyoxometalate (POM) and lanthanide (Ln) system. Within 1a, two identical penta-nuclear Eu2W3-cluster-encapsulated dimeric units {[Eu2(H2O)6W3O6][B-α-SeW9O33]2}4− are arranged in an ''open C-shaped'' configuration, interconnected by double tetra-dentate tar4− linkers. Moreover, 1a demonstrates notable stability and intense photoluminescence (PL) emission in an aqueous environment. This emission proves effective in discriminating the toxic chemical pollutant o-nitrophenol (o-NP) from its isomers m-nitrophenol (m-NP) and p-nitrophenol (p-NP), achieving highly selective and sensitive discrimination of o-NP with a low detection limit of 0.73 μM. The practical applicability of probe 1a was demonstrated in lake water, exhibiting suitable recoveries. The PL sensing mechanism involving static quenching and competitive absorption was elucidated finally. This accomplishment sets the groundwork for the deliberate synthesis of novel organic ligands and Ln-functionalized POM hybrids. Furthermore, it propels the exploration of POM materials for the recognition of environmental pollutants.

An alternative approach to defect-trapped Pt single-sites on a semiconductor is reported. Here, protruding Pt sites inhibit charge recombination and cause a tip effect which enhances H2 evolution yield rates with minimal co-catalyst loading.

Abstract Tendon heterotopic ossification (HO) is characterized by bone formation inside tendon tissue, which severely debilitates people in their daily life. Current therapies fail to promote functional tissue repair largely due to our limited understanding of HO pathogenesis. Here, we investigate the pathological mechanism and propose a potential treatment method for HO. Immunofluorescence assays showed that the Mohawk (MKX) expression level was decreased in human tendon HO tissue, coinciding with spontaneous HO and the upregulated expression of osteochondrogenic and angiogenic genes in the tendons of Mkx −/− mice. Single-cell RNA sequencing analyses of wild-type and Mkx −/− tendons identified three cell types and revealed the excessive activation of osteochondrogenic genes during the tenogenesis of Mkx −/− tendon cells. Single-cell analysis revealed that the gene expression program of angiogenesis, which is strongly associated with bone formation, was activated in all cell types during HO. Moreover, inhibition of angiogenesis by the small-molecule inhibitor BIBF1120 attenuated bone formation and angiogenesis in the Achilles tendons of both Mkx mutant mice and a rat traumatic model of HO. These findings provide new insights into the cellular mechanisms of tendon HO and highlight the inhibition of angiogenesis with BIBF1120 as a potential treatment strategy for HO.

In this paper, an AMOLED pixel circuit based on low-temperature poly-crystalline silicon and oxide (LTPO) thin-film transistors (TFTs) hybrid technology is proposed, which features only two transistors in a serial connection with OLED. The power supply can thus be reduced by $25{\sim }30$ % in the “Always-on-Display” (AOD) mode compared with the earlier LTPO pixel circuits which usually have three transistors in the current path and need a higher supply voltage. Furthermore, in addition to a strong suppressing ability to $\text{V}_{\mathrm{ th}}$ variations/shift, the proposed pixel circuit has an excellent compensation ability for current-resistance voltage drops (i.e., IR drop), which is also superior to the earlier LTPO ones where the IR drop has to be compensated externally. Therefore, the proposed LTPO pixel circuit is able to provide AMOLED displays with lower power consumption and higher display performance than the earlier ones.

The identification of geologic fluids and related fluid–rock interactions during diagenesis is the subject of much research in sedimentary petrology. Authigenic calcite potentially provides a record of geologic fluids and it occurs heterogeneously in the Upper Permian Wuerhe Formation (P3w) in the Shawan Sag, Junggar Basin, which has a complex history of geologic fluid activity. This provides an ideal opportunity to study the effectiveness of authigenic calcite in tracing fluids. We conducted optical, cathodoluminescence (CL), and scanning electron microscopic observations, as well as the major and trace element and stable carbon and oxygen isotopes of authigenic calcite. The results show that three generations of calcite were precipitated in the P3w Formation, and the diagenetic fluid was affected to varying degrees by paleo-meteoric water and hydrocarbon-bearing fluids. During early diagenesis, diagenetic fluid with low Mn contents precipitated the amorphous early-stage calcite (dark red in CL images, MnO 4% and δ13C of −25.7‰ to −14.9‰). Its carbon source was mainly CO2 produced by the decarboxylation of organic acids. The precipitation of abundant late-stage sC-depleted calcite suggests that the hydrocarbons were oxidized to organic acids in the reservoir. The two periods of hydrocarbon charging caused the dissolution of laumontite and the early-stage calcite, forming secondary minerals and dissolution pores, which increased the porosity and permeability of the rock. Therefore, authigenic calcite is a useful tracer of fluid properties, fluid–rock interactions, and alteration processes in petroliferous basins.

Fires lead to dramatic shifts in ecosystems and have a large impact on the biota. Soil organisms, especially soil fauna, are often used as indicators of environmental change. At present, minimal attention has been paid to using soil fauna as an indicator of environmental change after a fire. Here, a field survey of burnt herbaceous vegetation in semi-arid areas was conducted to determine the response of soil arthropods to fire and their short–term recovery after fire. Overall, the abundance and biomass of soil arthropods was more sensitive to fire than the number of groups. The number of soil arthropod groups, especially the dominant groups (mites and springtails), was not significantly affected by wildfires. At the unburned site, soil arthropod abundance showed significant seasonal shifts that may be related to the vegetation properties, temperature, and precipitation caused by seasonal changes. In contrast, soil arthropods at the burnt sites showed a delayed recovery and had only reached 56%–82%, 17%–54%, and 91%–190% of the biomass in the unburnt forest at the 3, 6, and 9 months after the burning event. Our findings of soil arthropod abundance changes in the present study suggest that fire-induced changes in soil and vegetation properties (e.g., AN, LT, and VC) were crucial factors for the changes in soil arthropod abundance in this semi-arid grassland. We conclude that fire disturbance reduces the seasonal sensitivity of soil arthropods by altering their habitat. This study furthers our understanding of wildfire impact recovery by documenting the short-term temporal dynamics of soil arthropods.

Abstract Polypropylene (PP) is being considered as a suitable alternative to the cross‐linked polyethylene (XLPE) insulation as the latter is prone to the space charge accumulation when subjected to the voltage polarity reversals in line‐commutated converter high voltage direct current transmission. This novel contribution correlates the space charge accumulation with the trap distribution inside XLPE and PP under the polarity reversal condition. The pulse electro‐acoustic and surface potential decay methods are used to measure the space charge and trap distributions, respectively. These measurements are carried at different poling durations (1 and 6 h at each polarity) and cycles of voltage polarity reversal (one and three cycles) at the electric field of 60 kV/mm. The XLPE shows more homo and hetero charge accumulation than PP. Dominant shallow traps in the XLPE are responsible for the space charge accumulation, whereas deep traps with higher trap density inhibit space charge accumulation within the PP. Furthermore, the positive and negative threshold fields for the space charge accumulation are measured. It is observed that the space charge can be easily accumulated under the negative electric field. Interestingly, the space charge decays rapidly inside the XLPE with the increased number of polarity reversal cycle. A valid theoretical model is developed to explain the space charge accumulation inside the XLPE and PP. The field‐assisted ionization plays a key role in the space charge accumulation inside the XLPE.

Summary: We described a challenge named “Diabetic Retinopathy (DR)—Grading and Image Quality Estimation Challenge” in conjunction with ISBI 2020 to hold three sub-challenges and develop deep learning models for DR image assessment and grading. The scientific community responded positively to the challenge, with 34 submissions from 574 registrations. In the challenge, we provided the DeepDRiD dataset containing 2,000 regular DR images (500 patients) and 256 ultra-widefield images (128 patients), both having DR quality and grading annotations. We discussed details of the top 3 algorithms in each sub-challenges. The weighted kappa for DR grading ranged from 0.93 to 0.82, and the accuracy for image quality evaluation ranged from 0.70 to 0.65. The results showed that image quality assessment can be used as a further target for exploration. We also have released the DeepDRiD dataset on GitHub to help develop automatic systems and improve human judgment in DR screening and diagnosis. The bigger picture: Diabetic retinopathy (DR) is the most common disease caused by diabetes. Challenges are held to address real-world issues encountered in the design of DR automated screening systems to advance the technology in this area. Thus, we described a challenge named ''Diabetic Retinopathy (DR)—Grading and Image Quality Estimation Challenge'' in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI 2020) for fundus image assessment and DR grading. The scientific community responded positively to the challenge. In the challenge, we provided a deep DR image dataset (DeepDRiD) containing regular DR images and ultra-widefield (UWF) DR images, both having image quality and DR grading diagnosis. We discussed details of the three best algorithms in each sub-challenges. The results by the top algorithms showed that image quality assessment can be used as a target for further exploration.

The sulfuric acid industry produces large volumes of spent catalyst containing vanadium. To develop an efficient method for vanadium recovery, hydrogen peroxide was used to oxidize sulfur in the spent catalyst, forming sulfuric acid, which, in turn, leached the metals from the catalyst. Experimental results showed that the leaching efficiency of vanadium gradually increased with hydrogen peroxide concentration; other parameters had minor effects. The hydrogen peroxide concentration, stirring rate, and pH had negative effects on leaching percent of potassium. Leaching efficiency of iron decreased with an increase in leaching time, stirring rate, and pH; with the increase in hydrogen peroxide concentration and liquid:solid ratio, leaching efficiency of iron first increased and then decreased. The optimum leaching conditions for vanadium were hydrogen peroxide concentration of 148 g/L, leaching time of 5 min, leaching temperature of 25 °C, stirring rate of 300 r/m, and liquid:solid ratio of 3:1, and leaching efficiencies of vanadium, potassium, and iron were 92.2%, 48.2%, and 46.3%, respectively. For potassium and iron, the leaching efficiencies of 70.9% and 70.5% were achieved using pure water leaching under the conditions of leaching time of 30 min, liquid to solid ratio of 4:1, and the temperature of 25 °C.

Under the threat of global climate change, China has proposed a dual carbon goal of peak carbon and carbon neutrality. As the vital carrier for territorial spatial planning, production–living–ecological (PLE) spaces drive carbon emissions and are important to the dual carbon goals. In this study, carbon emissions and sinks of PLE spaces in cities in Heilongjiang Province from 2005 to 2020 were calculated and spatial–temporal changes were analyzed. The carbon emission structure was analyzed in segmentation sectors. The land use changes and socioeconomic factors on carbon emissions were analyzed, and emission reduction strategies were implemented. The results show the following: (1) Carbon emissions from production and living spaces increased yearly. Carbon sinks were smaller than emissions, but capacity was stable. (2) Higher-emission cities were concentrated in southwest Heilongjiang, and carbon emission differences between regions gradually increased. (3) Among carbon emission sectors, agricultural and household made up smaller proportions, while animal husbandry, industrial, transportation, and traffic travel contributed most. Carbon emission structures were transformed by adjusting urban development and industrial structure. (4) For most cities, industrial space was the main emission space, but agricultural production and urban–rural living spaces dominated in some cities. (5) GDP, urbanization rate, and area of city paved roads suppressed emissions in cities with decreased carbon emission grades. The industrial structure and coal consumption inhibited emissions in cities with maintaining and increasing carbon emissions grades.

Hereditary ophthalmopathy is a well-described threat to human visual health affecting millions of people. Gene therapy for ophthalmopathy has received widespread attention with the increasing understanding of pathogenic genes. Effective and safe delivery of accurate nucleic acid drugs (NADs) is the core of gene therapy. Efficient nanodelivery and nanomodification technologies, appropriate targeted genes, and the choice of drug injection methods are the guiding lights of gene therapy. Compared with traditional drugs, NADs can specifically change the expression of specific genes or restore the normal function of mutant genes. Nanodelivery carriers can improve targeting and nanomodification can improve the stability of NADs. Therefore, NADs, which can fundamentally solve pathogeny, hold great promise in the treatment of ophthalmopathy. This paper reviews the limitations of ocular disease treatment, discusses the classification of NADs in ophthalmology, reveals the delivery strategies of NADs to improve bioavailability, targeting, and stability, and summarizes the mechanisms of NADs in ophthalmopathy.

Iron (Fe) deficiency in alkaline calcium soil is a problem that needs to be solved urgently as Fe is an essential and commonly limiting nutrient for plants. Endophytic fungus, Phomopsis liquidambaris (P. liquidambaris), has been reported to promote Fe absorption in peanuts (Arachis hypogaea L.), however, the mechanisms remain unclear. Under prolonged Fe deficiency, an increase in hydrogen peroxide (H2O2) often triggers a series of signaling events and leads to the inhibition of Fe acquisition. The main purpose of this study was to explore whether and how the endophytic fungus P. liquidambaris promote Fe absorption in peanut through regulating H2O2 and assisting in resisting oxidative stress. In this study, we detected the Fe deficiency-induced transcription factor (FIT), Fe2+ transporter (IRT1), and ferric reduction oxidase 2 (FRO2) of peanuts, and confirmed that they were negatively related to Fe concentration. Similarly, FIT, IRT1, and FRO2 were also inhibited by H2O2. The addition of P. liquidambaris reduces H2O2 under Fe-deficiency with an increase in Fe content, while the exogenous addition of H2O2 further decreases it, and the addition of catalase (CAT) under Fe-deficiency reverses this phenomenon. Through transcriptome analysis, we proved that the expression of FIT, IRT1, FRO2 and CAT are consistent with our hypothesis, and P. liquidambaris has a stress-mitigating effect on peanuts mainly via CAT, glutathione peroxidase, and malondialdehyde. Our study proved the Fe-absorption promoting effect and stress mitigation effect of P. liquidambaris under Fe-deficiency in peanuts, and their combined usage may help peanuts grow better

Phenanthrene cannot be effectively degraded in the agricultural production systems and it is greatly hazardous for food safety and human health. In our study, the remediation ability and mechanism of rice and endophytic fungus Phomopsis liquidambaris interaction on phenanthrene in the rice-growing environment were explored using laboratory and pot experiments. The results showed that plant-endophyte interaction had the potential to enhance remediation on phenanthrene contamination in the rice-growing environment. The content of phenanthrene in soil and rice (including leaves, roots, and grains) of the plant-endophyte interaction system was about 42% and 27% lower than of the non-inoculated treatment under 100 mg kg−1 treatment. The mechanism may be related to the improvement of plant growth, root activity, chlorophyll content, ATP energy supply, and antagonistic ability of rice to promote the absorption of phenanthrene in the rice-growing environment, and then the phenanthrene absorbed into the rice was degraded by improving the phenanthrene degrading enzyme activities and gene relative expression levels of P. liquidambaris during plant-endophyte interaction. Moreover, the plant-endophyte interaction system could also promote rice growth and increase rice yield by over 20% more than the control under 50 mg kg−1 treatment. This study indicated a promising potential of the plant-endophyte interaction system for pollution remediation in agriculture.

Abstract Objectives A pneumonia associated with 2019 novel coronavirus (2019-nCoV, subsequently named SARS-CoV2) emerged worldwide since December, 2019. We aimed to describe the epidemiological characteristics of 2019 coronavirus disease (COVID-19) in Shaanxi province of China. Results 1. Among the 245 patients, 132 (53.9%) were males and 113 (46.1%) were females. The average age was 46.15 ± 16.43 years, ranging from 3 to 89 years. 2. For the clinical type, 1.63% (4/245) patients were mild type, 84.90% (208/245) were moderate type, 7.76% (19/245) were severe type, 5.31% (13/245) were critical type and only 0.41% (1/245) was asymptomatic. 3. Of the 245 patients, 116 (47.35%) were input case, 114 (46.53%) were non-input case, and 15 (6.12%) were unknown exposure. 4. 48.57% (119/245) cases were family cluster, involving 42 families. The most common pattern of COVID-19 family cluster was between husband and wife or between parents and children.

The current study aimed to explore the role of the circular RNA circ‐TCF4.85 and its downstream target microRNA‐486‐5p (miR‐486‐5p) in hepatocellular carcinoma (HCC) development. Circ‐TCF4.85 was detected to be highly expressed in HCC tissues. Next, we found that silencing of circ‐TCF4.85 repressed HCC cell proliferation, invasion, and migration, while enhancing apoptosis. In addition, biotin‐coupled probe pull‐down and miRNA capture assays, as well as fluorescence in situ hybridization, confirmed that circ‐TCF4.85 could bind to miR‐486‐5p. In rescue experiments, miR‐486‐5p had the potential to eliminate the tumor‐suppressive effects of circ‐TCF4.85 knockdown in HCC. Moreover, miR‐486‐5p was shown to target ABCF2 gene, which was positively regulated by circ‐TCF4.85. Finally, nude mice subcutaneously injected with si‐circ‐TCF4.85‐transfected HCC cells presented with inhibited xenograft tumor formation in vivo. Taken together, our results reveal that silencing of circ‐TCF4.85 suppresses HCC progression via miR‐486‐5p‐targeted inhibition of ABCF2.

This paper introduces an optimization method (SCE-SR) that combines shuffled complex evolution (SCE) and stochastic ranking (SR) to solve constrained reservoir scheduling problems, ranking individuals with both objectives and constrains considered. A specialized strategy is used in the evolution process to ensure that the optimal results are feasible individuals. This method is suitable for handling multiple conflicting constraints, and is easy to implement, requiring little parameter tuning. The search properties of the method are ensured through the combination of deterministic and probabilistic approaches. The proposed SCE-SR was tested against hydropower scheduling problems of a single reservoir and a multi-reservoir system, and its performance is compared with that of two classical methods (the dynamic programming and genetic algorithm). The results show that the SCE-SR method is an effective and efficient method for optimizing hydropower generation and locating feasible regions quickly, with sufficient global convergence properties and robustness. The operation schedules obtained satisfy the basic scheduling requirements of reservoirs. Keywords: Reservoir scheduling, Optimization method, Constraint handling, Shuffled complex evolution, Stochastic ranking