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USP25 encodes ubiquitin-specific protease 25, a key member of the deubiquitinating enzyme family that is involved in neural fate determination. Although abnormal expression in Down's syndrome was reported previously, the specific role of USP25 in human diseases has not been defined. In this study, we performed trio-based whole exome sequencing in a cohort of 319 cases (families) with generalized epilepsy of unknown aetiology. Five heterozygous USP25 variants, including two de novo and three co-segregated variants, were determined in eight individuals affected by generalized seizures and/or febrile seizures from five unrelated families. The frequency of USP25 variants showed a significantly high aggregation in this cohort compared with the East Asian population and all populations in the gnomAD database. The mean age at onset of febrile and afebrile seizures were 10 months (infancy) and 11.8 years (juvenile), respectively. The patients achieved seizure freedom, except that one had occasional nocturnal seizures at the last follow-up. Two patients exhibited intellectual disability. Usp25 was expressed ubiquitously in mouse brain with two peaks, on embryonic Days 14–16 and postnatal Day 21, respectively. In human brain, likewise, USP25 is expressed in the fetus/early childhood stage and with a second peak at ∼12–20 years old, consistent with the seizure onset age in patients during infancy and in juveniles. To investigate the functional impact of USP25 deficiency in vivo , we established Usp25 knockout mice, which showed increased seizure susceptibility compared with wild-type mice in a pentylenetetrazol-induced seizure test. To explore the impact of USP25 variants, we used multiple functional detections. In HEK293 T cells, the variant associated with a severe phenotype (p.Gln889Ter) led to a significant reduction of mRNA and protein expressions but formed stable truncated dimers with an increment of deubiquitinating enzyme activities and abnormal cellular aggregations, indicating a gain-of-function effect. The p.Gln889Ter and p.Leu1045del variants increased neuronal excitability in mouse brain, with a higher firing ability in p.Gln889Ter. These functional impairments align with the severity of the observed phenotypes, suggesting a genotype–phenotype correlation. Hence, a moderate association between USP25 and epilepsy was noted, indicating that USP25 is potentially a predisposing gene for epilepsy. Our results from Usp25 null mice and the patient-derived variants indicated that USP25 would play an epileptogenic role via loss-of-function or gain-of-function effects. The truncated variant p.Gln889Ter would have a profoundly different effect on epilepsy. Together, our results underscore the significance of USP25 heterozygous variants in epilepsy, thereby highlighting the critical role of USP25 in the brain. [ABSTRACT FROM AUTHOR]

Per- and polyfluoroalkyl substances (PFASs) are emerging persistent organic pollutants (POPs). In this study, 47 surface sediment samples were collected from the Yellow River Delta wetland (YRDW) to investigate the occurrence, spatial distribution, potential sources, and ecological risks of PFASs. Twenty-three out of 26 targeted PFASs were detected in surface sediment samples from the YRDW, with total ∑23PFASs concentrations ranging from 0.23 to 16.30 ng g−1 dw and a median value of 2.27 ng g−1 dw. Perfluorooctanoic acid (PFOA), perfluorobutanoic acid (PFBA) and perfluorooctanesulfonic acid (PFOS) were the main contaminants. The detection frequency and concentration of perfluoroalkyl carboxylic acids (PFCAs) were higher than those of perfluoroalkanesulfonic acids (PFSAs), while those of long-chain PFASs were higher than those of short-chain PFASs. The emerging PFASs substitutes were dominated by 6:2 chlorinated polyfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA). The distribution of PFASs is significantly influenced by the total organic carbon content in the sediments. The concentration of PFASs seems to be related to human activities, with high concentration levels of PFASs near locations such as beaches and villages. By using a positive matrix factorization model, the potential sources of PFASs in the region were identified as metal plating mist inhibitor and fluoropolymer manufacturing sources, metal plating industry and firefighting foam and textile treatment sources, and food packaging material sources. The risk assessment indicated that PFASs in YRDW sediments do not pose a significant ecological risk to benthic organisms in the region overall, but PFOA and PFOS exert a low to moderate risk at individual stations. [ABSTRACT FROM AUTHOR]

A dual-enzyme cascade catalytic system (Cu-rGO-Fe3O4-GA-CEL-PEI-GOD) was prepared by co-immobilizing cellulase (CEL) and glucose oxidase (GOD) on a nanocomposite (Cu-rGO-Fe3O4) to efficiently catalyze the conversion of carboxymethyl cellulose (CMC) to gluconic acid. A layer-by-layer strategy was used by adding polyethyleneimine (PEI) to allow the upper enzyme layer to attach to the lower neighboring layer, increasing the loading capacity of the support. The loading capability of CEL and GOD on Cu-rGO-Fe3O4-GA-CEL-PEI-GOD were 55.034 mg g−1 and 12.4 mg g−1, respectively. The specific activity of CEL on Cu-rGO-Fe3O4-GA-CEL was 74.3 U·g−1, and that of immobilized CEL after cross-linking PEI was 25.45 U·g−1, which could retain 34.253% of the enzyme activity. The specific activity of GOD on Cu-rGO-Fe3O4-GA-CEL-PEI-GOD was 30.9 U·g−1. The carrier Cu-rGO-Fe3O4 has peroxidase-like activity, which can timely remove harmful H2O2 to the enzyme, thereby improving the yield of gluconic acid and the stability of biocatalysts. The yield of gluconic acid with Cu-rGO-Fe3O4-GA-CEL-PEI-GOD reached 96.04% within 2 h, higher than the control systems for comparison. In addition, the Cu-rGO-Fe3O4-GA-CEL-PEI-GOD maintained 82.61% of catalytic activity even after undergoing seven cycles of reaction. The dual-enzyme catalytic systems had shallow temperature and pH optima of 40 °C and 4.5. Such a chemoenzymatic cascade system provides a new strategy for the conversion from CMC to gluconic acid in one-step. Enzymatic conversion of sodium carboxymethyl cellulose (CMC-Na) to gluconic acid. [ABSTRACT FROM AUTHOR]

Prussian blue (PB), as a promising inorganic electrochromic material (ECM), has been widely used in smart windows, displays, sensors, etc. However, there are still many challenges for PB to achieve high electrochromic performance. Herein, we synthesized nitrogen-doped carbon dots-modified PB film (defined as PB@N-CDs) with a sandwich-like structure by a simple stepwise electrodeposition method. The carbon dots show an obvious advantage in ultrafast electron transfer ability, which can reduce charge loss during the transfer process, improve the electrochemical activity on both sides of PB, and thus facilitate a rapid electrochromic response. Furthermore, the surface of nitrogen-doped carbon dots contains multiple organic functional groups, which widen the movement path of K+ ions under electrostatic adsorption. Impressively, the PB@N-CDs film exhibits a short bleaching/coloring time (0.5/0.9 s) and a superior optical modulation range (78.6%). Particularly, the coloring efficiency has been significantly improved to 137.71 cm2/C (at 700 nm). All of these results open up new avenues for developing high-performance PB-based ECMs and promoting their applications in corresponding electrochromic devices (ECDs) and smart windows. [ABSTRACT FROM AUTHOR]

Silicon‐based materials are regarded as the most promising negative electrode materials for next‐generation high‐energy lithium ion batteries due to their high theoretical capacity, low lithiation plateau and low cost, but they still suffer from dramatic volume variation during charge/discharge and sluggish kinetics, substantially restricting their practical applications. Recently, 2D MXenes are demonstrated to improve the electrochemical performances of Si‐based materials owing to their metallic conductivity, large surface aspect ratio, rich surface chemistry, good mechanical strength, etc. Serving as conductive host, MXenes can alleviate the volume expansion of Si during lithiation, enhance the electronic conductivity of the composite and facilitate the electron/ion transport, thus making the resultant Si/MXene composites exhibit excellent performance as negative electrodes of secondary batteries. Herein, an overview toward the recent advances of Si/MXene nanocomposites is presented for lithium storage applications. The preparation strategies and structural characteristics of the Si/MXene nanocomposites are introduced. The applications of diverse Si/MXene nanostructures such as powders, 3D architectures, films and fibers, in lithium ion batteries with corresponding structure‐performance relationships are discussed. Finally, the challenges and perspectives for the future research of Si/MXene nanocomposites are highlighted, aiming to provide a fundamental reference in designing advanced Si/MXene nanocomposites for high‐energy lithium ion batteries. [ABSTRACT FROM AUTHOR]

Background: Diarrhea is a common complication of hematopoietic stem cell transplantation (HSCT) and is associated with substantial morbidity, but its etiology is often unknown. Etiologies of diarrhea in this population include infectious causes, chemotherapy- or medication-induced mucosal injury and graft-versus-host disease (GVHD). Distinguishing these potential causes of diarrhea is challenging since diarrheal symptoms are often multifactorial, and the etiologies often overlap in transplant patients. The objectives of this study were to evaluate whether the FilmArray gastrointestinal (GI) panel would increase diagnostic yield and the degree to which pre-transplantation colonization predicts post-transplantation infection. Methods: From November 2019 to February 2021, a total of 158 patients undergoing HSCT were prospectively included in the study. Stool specimens were obtained from all HSCT recipients prior to conditioning therapy, 28 ± 7 days after transplantation and at any new episode of diarrhea. All stool samples were tested by the FilmArray GI panel and other clinical microbiological assays. Results: The primary cause of post-transplantation diarrhea was infection (57/84, 67.86%), followed by medication (38/84, 45.24%) and GVHD (21/84, 25.00%). Ninety-five of 158 patients were colonized with at least one gastrointestinal pathogen before conditioning therapy, and the incidence of infectious diarrhea was significantly higher in colonized patients (47/95, 49.47%) than in non-colonized patients (10/63, 15.87%) (P < 0.001). Fourteen of 19 (73.68%) patients who were initially colonized with norovirus pre-transplantation developed a post-transplantation norovirus infection. Twenty-four of 62 (38.71%) patients colonized with Clostridium difficile developed a diarrheal infection. In addition, FilmArray GI panel testing improved the diagnostic yield by almost twofold in our study (55/92, 59.78% vs. 30/92, 32.61%). Conclusions: Our data show that more than half of pediatric patients who were admitted for HSCT were colonized with various gastrointestinal pathogens, and more than one-third of these pathogens were associated with post-transplantation diarrhea. In addition, the FilmArray GI panel can increase the detection rate of diarrheal pathogens in pediatric HSCT patients, but the panel needs to be optimized for pathogen species, and further studies assessing its clinical impact and cost-effectiveness in this specific patient population are also needed. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

As the primary variable load of bridges, vehicle load is an important parameter for bridge health monitoring. However, traditional Weigh-in-Motion (WIM) systems and the commonly used method of placing sensors on the bridge are challenging to apply in load monitoring for many small and medium-sized bridges. Therefore, this paper proposes a bridge vehicle load identification method based on traffic surveillance video data. Leveraging the surveillance video data on the bridge, without introducing additional hardware devices, the displacement of target points is detected through sub-pixel level image detection algorithms, enabling non-contact measurement of bridge structural response through imaging. A spatiotemporal relationship model of structural displacement, vehicle load, and load distribution is established to solve for vehicle load. Finally, model bridge tests under various loading conditions and engineering practice experiments are conducted to validate the feasibility of the method. The results of the model bridge tests show that the structural displacement measured using traffic video measurement has a deviation of less than 10% compared to the measurements obtained using contact displacement sensors (LVDT), and it can accurately reflect the displacement characteristics of the structure. The results of the field tests demonstrate that the average estimation deviation for heavy vehicle loads ranging from 12 to 18 tons is approximately 18%, meeting the engineering requirements. The proposed method can provide load statistical information for the extensive health monitoring of small and medium-sized bridges and offer a new technical pathway for obtaining bridge load information. [ABSTRACT FROM AUTHOR]

NUS1 encodes the Nogo-B receptor, a critical regulator for unfolded protein reaction (UPR) signaling. Although several loss-of-function variants of NUS1 have been identified in patients with developmental and epileptic encephalopathy (DEE), the role of the NUS1 variant in Lennox-Gastaut syndrome (LGS), a severe child-onset DEE, remains unknown. In this study, we identified two de novo variants of NUS1, a missense variant (c.868 C > T/p.R290C) and a splice site variant (c.792-2 A > G), in two unrelated LGS patients using trio-based whole-exome sequencing performed in a cohort of 165 LGS patients. Both variants were absent in the gnomAD population and showed a significantly higher observed number of variants than expected genome-wide. The R290C variant was predicted to damage NUS1 and decrease its protein stability. The c.792-2 A > G variant caused premature termination of the protein. Knockdown of NUS1 activated the UPR pathway, resulting in apoptosis of HEK293T cells. Supplementing cells with expression of wild-type NUS1, but not the mutant (R290C), rescued UPR activation and apoptosis in NUS1 knockdown cells. Compared to wild-type Drosophila, seizure-like behaviors and excitability in projection neurons were significantly increased in Tango14 (homolog of human NUS1) knockdown and Tango14R290C/+ knock-in Drosophila. Additionally, abnormal development and a small body size were observed in both mutants. Activated UPR signaling was also detected in both mutants. Thus, NUS1 is a causative gene for LGS with dominant inheritance. The pathogenicity of these variants is related to the UPR signaling activation, which may be a common pathogenic mechanism of DEE. [ABSTRACT FROM AUTHOR]

As a technology for water landscape performance that considers landscape, ecological, and social effects, nature-based solutions play a crucial role in enhancing the functionality of integrated ecosystem services on the micro-scale. This study conducted a systematic investigation into the landscape performance of the "Clear as a Drain" composite sponge facility at Handan Garden Expo Park. The following conclusions were drawn: (1) In terms of ecological restoration support services, the "Clear as a Drain" artificial wetland exhibited diverse habitat types, a rich variety of plant species specific to the site's region, and high plant diversity indices for shrubs (1.776) and herbaceous aquatic plants (3.352). Reclaimed water reused in the artificial terraced wetland promoted plant growth and diversity while contributing to site self-rehabilitation; plants also significantly contributed to carbon fixation, oxygen release, and carbon emission reduction. (2) Regarding ecological restoration regulation services, the artificial wetland effectively purified reclaimed water with substantial improvements observed in incoming water quality during spring, summer, and autumn—particularly notable purification effects were observed during the summer months. Pollutant reduction rates for COD, BOD5 ammonia nitrogen, TP, and TN reached 75.8%, 72.1%, 93.8%, 96.7%, and 90.3%, respectively; different independent subsystems within the wetland demonstrated distinct advantages in pollutant removal; park plants displayed strong air purification capabilities; annual energy savings from park plants could fully cover daily energy consumption for nearby residents. This case could serve as guidance for scientific management and design parameter optimization of other composite sponge facilities. [ABSTRACT FROM AUTHOR]

Investigating the spatial distribution characteristics of the interaction between soil salinity and moisture is crucial in revealing moisture–salinity interaction in semi-arid farmland. The sampling of soil was performed on the second (S1), fifth (S2), eighth (S3), eleventh (S4), and fourteenth (S5) days after the erosive rainfall. The multifractal method was used to analyze spatial distribution parameters of soil moisture and salinity under the different stages. The findings showed that the soil moisture content decreased from 22.44% to 12.73%, while the salinity increased from 0.71 to 1.18 g kg–1 after the rainfall. As the amount of moisture in the soil decreased, the variability in the distribution of moisture initially increased from S1 to S3 and then decreased, while the salinity content also decreased. The spatial distribution of soil moisture and salinity content showed a strong correlation at S3 to S4 (with the relative water content of soil ranging from 0.52 to 0.75), indicating a significant coupling effect in these stages. However, the distribution of soil salinity was not uniform under high moisture content conditions (S1 to S2), as it was leached unevenly by rainfall, and under low moisture content conditions (S5), it precipitated, resulting in a low correlation between the spatial distribution of soil moisture and salinity content. This research has provided insight into the coupling dynamics of soil moisture and salinity content, revealing the mechanisms governing their spatial distribution in dryland agricultural regions. [ABSTRACT FROM AUTHOR]

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

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

Background: This retrospective study assessed the efficacy and safety of ketogenic diet therapies in children with epilepsy caused by SLC2A1 genetic mutations and glucose transporter type 1 deficiency syndrome. Methods: Pediatric patients with epilepsy symptoms admitted to our medical center between January 2017 and October 2021 were included if they presented with an SLC2A1 genetic mutation on whole-exome sequencing. We analyzed the patients' convulsions and treatment with antiepileptic drugs. The patients were followed up at different time periods after ketogenic diet therapies. Results: Six patients with SLC2A1 mutations were included in this study. The patients had seizures of different types and frequencies, and they took antiepileptic drugs to relieve their symptoms. They were then treated with a ketogenic diet for at least four months. We analyzed epilepsy control rates at 1, 2, 3, 6, and 12 months after ketogenic diet treatment. All patients were seizure-free within a month of receiving the diet therapy. All patients were followed up for six months, three were followed up for 12 months after the treatment, and there was no recurrence of epilepsy during this period. After antiepileptic drug withdrawal, none of the patients experienced seizure relapse when receiving ketogenic diet treatment alone. No severe adverse events occurred during the therapy. Conclusions: Ketogenic diet therapy is very effective and safe for the treatment of epilepsy caused by SLC2A1 mutations. Therefore, patients with glucose transporter type 1 deficiency syndrome caused by SLC2A1 mutations should begin ketogenic diet treatment as soon as possible. [ABSTRACT FROM AUTHOR]

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

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

To identify the key parameters and develop accurate experimental models of detachment and transport, splash detachment and transport of loess soil were investigated in relation to the rainfall characteristics and slope. The experiment was conducted under 25 combinations of five rainfall intensities (60, 84, 108, 132 and 156 mm h−1) and five slope gradients (0°, 5°, 10°, 15° and 20°), using a custom splash pan. Raindrop characteristics (diameter, velocity and kinetics) and splash mass were measured in downslope and upslope. The results indicated that rainfall intensity and slope contributed 94.77% and 0.46%, respectively, to the detachment rate, and 24.39% and 67.82%, respectively, to the transport rate. From a holistic viewpoint, the positive effect of slope became more visible on the detachment rate when the rainfall intensity exceeded 108 mm h−1, and on the transport rate when the slope exceeded 15°. Based on the rainfall simulator in this study, the rainfall kinetic energy (KE, J), raindrop median particle size (D50, mm) and raindrop terminal velocity (V, m s−1) all increased with increasing rainfall intensity (I) within the 60~108 mm h−1 range but decreased with increasing rainfall intensity within the 132~156 mm h−1 range. The rainfall intensity and raindrop characteristics (D50/V/KE) are the key parameters of splash detachment (Dr, g·m−2 min−1), and three detachment models were developed: (1) Dr = 0.1153 I1.09D500.79 (R2 = 0.99, NSE = 0.98, p < 0.01); (2) Dr = 0.0162 I1.11V1.22 (R2 = 0.99, NSE = 0.99, p < 0.01); and (3) Dr = 0.0813 I1.10KE0.18 (R2 = 0.99, NSE = 0.99, p < 0.01). The rainfall intensity and slope are the key parameters for splash transport (Tr, g·m−2 min−1), and the developed transport models could be expressed as: (1) Tr = 0.00657 I1.343S0.116 (R2 = 0.914, NSE = 0.874, p < 0.01) (slopes of 0°, 5° and 10°) and (2) Tr = 0.00218 I1.165S1.033 (R2 = 0.986, NSE = 0.986, p < 0.01) (slopes of 15° and 20°). The results of this study could enhance the understanding of soil splash detachment and transport on loess slopes. [ABSTRACT FROM AUTHOR]

The study of neuroimmune crosstalk and the involvement of neurotransmitters in inflammation and bone health has illustrated their significance in joint-related conditions. One important mode of cell-to-cell communication in the synovial fluid (SF) is through extracellular vesicles (EVs) carrying microRNAs (miRNAs). The role of neurotransmitter receptors in the pathogenesis of inflammatory joint diseases, and whether there are specific miRNAs regulating differentially expressed HTR2A, contributing to the inflammatory processes and bone metabolism is unclear. Expression of neurotransmitter receptors and their correlated inflammatory molecules were identified in rheumatoid arthritis (RA) and osteoarthritis (OA) synovium from a scRNA-seq dataset. Immunohistochemistry staining of synovial tissue (ST) from RA and OA patients was performed for validation. Expression of miRNAs targeting HTR2A carried by SF EVs was screened in low- and high-grade inflammation RA from a public dataset and validated by qPCR. HTR2A reduction by target miRNAs was verified by miRNAs mimics transfection into RA fibroblasts. HTR2A was found to be highly expressed in fibroblasts derived from RA synovial tissue. Its expression showed a positive correlation with the degree of inflammation observed. 5 miRNAs targeting HTR2A were decreased in RA SF EVs compared to OA, three of which, miR-214-3p, miR-3120-5p and miR-615-3p, mainly derived from monocytes in the SF, were validated as regulators of HTR2A expression. The findings suggest that fibroblast HTR2A may play a contributory role in inflammation and the pathogenesis of RA. Additionally, targeting miRNAs that act upon HTR2A could present novel therapeutic strategies for alleviating inflammation in RA. [ABSTRACT FROM AUTHOR]

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

Background: Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease characterized by the presence of numerous autoantibodies. The interaction of infectious agents (viruses, bacteria and parasites) and a genetically susceptible host may be a key mechanism for SLE. Toxoplasma gondii is a widespread intracellular parasite that has been implicated in the pathogenesis of autoimmune diseases. However, the relationship between T. gondii infection and the increased risk of SLE in Chinese populations remains unclear. Methods: The seroprevalence of T. gondii infection was assessed in 1771 serum samples collected from Chinese individuals (908 healthy controls and 863 SLE patients) from different regions of China using an enzyme-linked immunosorbent assay. Serum autoantibodies and clinical information were obtained and analysed. Results: Our observations revealed a higher prevalence of anti-T. gondii antibodies (ATxA) immunoglobulin G (IgG) in serum samples from SLE patients (144/863, 16.7%) than in those from the healthy controls (53/917, 5.8%; P < 0.0001), indicating a 2.48-fold increased risk of SLE in the ATxA-IgG+ population, after adjustment for age and sex (95% confidence interval [CI] 1.70–3.62, P < 0.0001). ATxA-IgG+ SLE patients also showed a 1.75-fold higher risk of developing moderate and severe lupus symptoms (95% CI 1.14–2.70, P = 0.011) compared to ATxA-IgG− patients. Relative to ATxA-IgG− patients, ATxA-IgG+ patients were more likely to develop specific clinical symptoms, including discoid rash, oral ulcer, myalgia and alopecia. Seven antibodies, namely anti-ribosomal RNA protein (rRNP), anti-double stranded DNA (dsDNA), anti-cell membrane DNA (cmDNA), anti-scleroderma-70 (Scl-70), anti-cardiolipin (CL), anti-beta2-glycoprotein-I (B2GPI) and rheumatoid factor (RF), occurred more frequently in ATxA-IgG+ patients. When combined with anti-dsDNA and RF/anti-rRNP/anti-cmDNA/ESR, ATxA-IgG significantly increased the risk for severe lupus. Conclusions: Our results suggest that ATxA-IgG may be a significant risk factor for SLE prevalence and severity in Chinese populations. [ABSTRACT FROM AUTHOR]

With the rapid development of the economy and information services, there is an increasing demand for indoor positioning. However, Global Navigation Satellite System (GNSS) signals face difficulties in penetrating buildings, making indoor positioning challenging. As a complementary solution to outdoor GNSS signals, pseudolites have shown promising results in various scenarios, and have become one of the research hotspots in the field of indoor positioning. Previous studies on indoor positioning with pseudolites have focused on issues such as initial position determination and carrier phase ambiguity resolution. However, most of these studies have remained in the research stage due to data post-processing and complex calculations. To overcome the limitations associated with the aforementioned factors, this paper proposes a real-time indoor positioning method that utilizes only a smartphone equipped with a built-in GNSS chip. By effectively obtaining pseudolite signal information, the smartphone establishes a simple model based on the distance and received power between the pseudolite and the smartphone. Kalman filtering is employed to mitigate the effects of multipath and occlusion. This simple and low-complexity model enables fast estimation of the user's distance from the pseudolite, thereby facilitating indoor positioning services. In this paper, the effectiveness and low complexity of the method are verified through data collection and experiments in the actual scene of the underground garage. The valuation results show that the root mean square error (RMSE) of its navigation and positioning is better than 3 m, which can meet the needs of daily life applications. [ABSTRACT FROM AUTHOR]

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

Systemic lupus erythematosus (SLE) is complex autoimmune disease with heterogenous manifestations, unpredictable disease course and response to treatment. One of the critical needs in SLE management is the identification of reliable biomarkers that can aid in early diagnosis, accurate monitoring of disease activity, and assessment of treatment response. In the current review, we focus on the commonly affected organs (skin, kidney, and nervous system) in SLE to summarize the emerging biomarkers that show promise in disease diagnosis, monitoring and treatment response assessment. The subtitles within each organ domain were determined based on the most relevant and promising biomarkers for that specific organ damage. Biomarkers have the potential to significantly benefit the management of SLE by aiding in diagnosis, disease activity monitoring, prognosis, and treatment response assessment. However, despite decades of research, none has been validated and implemented for routine clinical use. Novel biomarkers could lead to the development of precision medicine for SLE, guide personalized treatment, and improve patient outcomes. Challenges in biomarker research in SLE include defining clear and clinically relevant questions, accounting for the heterogeneity of SLE, and confirming initial findings in larger, multi-center, multi-ethnic, independent cohorts that reflect real-world clinical scenarios. [ABSTRACT FROM AUTHOR]

Objective. This study aimed to compare the attitudes and preferences on cancer diagnosis disclosure (CDD) among suspicious lung cancer patients (SLCPs), lung cancer patients (LCPs), and their family members and to explore their associations with resilience. Methods. A cross-sectional study was conducted at Yunnan Cancer Hospital in China, from March to August 2022. A total of 1016 participants including 254 SLCP-family pairs and 254 LCP-family pairs completed self-administered questionnaires to assess their attitudes toward CDD and resilience. Continuous variables were expressed by means and standard deviations, while categorical variables were presented by numbers and percentages. The comparisons between groups were tested by using a t-test or chi-squared test. Associations between resilience and CDD attitudes in the four groups were estimated by multivariate logistic regression models. Results. Compared with LCPs, more SLCPs believed that patients should be informed of their cancer diagnoses (63.8% vs 43.7%, p < 0.001), and the distribution of the first one to know the diagnosis was disequilibrium (p < 0.05). The significant difference was identified in participants' attitudes toward patients being told the facts by resilience levels among the different groups. Subsequent multivariate logistic regression analyses showed that resilience was associated with participants' preference for patients being informed of their cancer diagnoses in the SLCPs group (adjusted OR: 1.87, 95% CI: 1.08–3.25), LCPs group (adjusted OR: 2.21, 95% CI: 1.32–3.74), and family of LCPs group (adjusted OR: 1.79, 95% CI: 1.04–3.12). We further performed a sensitivity analysis using quantiles of resilience. Conclusion. SLCPs and LCPs exhibited different attitudes towards CDD. Resilience plays a positive role in CDD. Our study suggests that healthcare practitioners should consider patients' diagnosis state when disclosing a cancer diagnosis and tailor their disclosure methods based on the patients' and families' preferences and resilience. Our findings provide important implications to guide future research and intervention programs to improve cancer diagnosis disclosure for SLCPs, LCPs, and their families. [ABSTRACT FROM AUTHOR]

Emerging contaminants (ECs) are gaining global attention owing to their widespread presence and adverse effects on human health. ECs comprise numerous composite types and pose a potential threat to the growth and functional traits of species and ecosystems. Although the occurrence and fate of ECs has been extensively studied, little is known about their long-term biological effects. This review attempts to gain insights into the unhindered connections and overlaps in aquatic ecosystems. Microplastics (MPs), one of the most representative ECs, are carriers of other pollutants because of their strong adsorption capacity. They form a complex of pollutants that can be transmitted to aquatic organisms and humans through the extended food chain, increasing the concentration of pollutants by tens of thousands of times. Adsorption, interaction and transport effects of emerging contaminants in the aquatic environment are also discussed. Furthermore, the current state of knowledge on the ecotoxicity of single- and two-pollutant models is presented. Herein, we discuss how aquatic organisms within complex food networks may be particularly vulnerable to harm from ECs in the presence of perturbations. This review provides an advanced understanding of the interactions and potential toxic effects of ECs on aquatic organisms. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases globally, leading to chronic disability and poor prognosis. One of the approaches for optimizing OA treatment is to find early effective diagnostic biomarkers. The contribution of microRNAs (miRNAs) in OA progression is now being increasingly recognized. This review provides a comprehensive summary on studies reporting the expression profiling of miRNAs in OA and associated signaling pathways. We performed a systematic search of the Embase, Web of Science, PubMed, and Cochrane library databases. This systematic review is reported according to the PRISMA checklist. Studies which identified miRNAs with aberrant expression compared to controls during OA progression were included, and a meta-analysis was performed. Results from the random effects model were provided as log10 odds ratios (logORs) and 95% confidence intervals. Sensitivity analysis was conducted to confirm the accuracy of the results. Subgroup analysis was conducted based on tissue source. The target genes of miRNAs identified in this study were extracted from the MiRWalk database, and these target genes were enriched in Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. A total of 191 studies reporting 162 miRNAs were included in our meta-analysis. Among them, 36 miRNAs distributed across 96 studies were expressed in the same direction in at least two studies (13 up-regulated and 23 down-regulated). Subgroup analysis of tissue source revealed that the highest number of studies was conducted using articular cartilage, where the most up-regulated miRNAs were miR-146a-5p (logOR 7.355; P < 0.001) and miR-34a-5p (logOR 6.955; P < 0.001), and the most down-regulated miRNAs were miR-127-5p (logOR 6.586; P < 0.001) and miR-140-5p (logOR 6.373; P < 0.001). Enrichment analysis of 752 downstream target genes of all identified miRNAs was performed, and the regulatory relationships among them were displayed. Mesenchymal stem cells and transforming growth factor-β were found to be the most important downstream effectors regulated by miRNA in OA. This study highlighted the importance of miRNA signaling in OA progression and identified a number of prominent miRNAs including miR-146a-5p, miR-34a-5p, miR-127-5p, and miR-140-5p which might be considered as potential biomarkers for OA. [ABSTRACT FROM AUTHOR]

The current expansion of building structures has created a demand for efficient and smart surface quality evaluation at the acceptance phase. However, the conventional approach mainly relies on manual work, which is labor-intensive, time-consuming, and unrepeatable. This study presents a systematic and practical solution for surface quality evaluation of indoor building elements during the acceptance phase using point cloud. The practical indoor scanning parameters determination procedure was proposed by analyzing the project requirements, room environment, and apparatus. An improved DBSCAN algorithm was developed by introducing a plane validation and coplanar checking to facilitate the surface segmentation from the point cloud. And a revised Least Median of Square-based algorithm was proposed to identify the best-fit plane. Afterwards, the flatness, verticality, and squareness were evaluated and depicted using a color-coded map based on the segmented point cloud. The experiment on an apartment showcases how the system improves the information flow and accuracy during building acceptance, resulting in a potentially smart acceptance activity. [ABSTRACT FROM AUTHOR]

A semi-analytical model for deterministic surface smoothing of fused silica below the evaporation temperature threshold is presented. Using this model, a method for calculating deterministic track depths for laser polishing fused silica is derived and validated with experiments. Model predictions were in good agreement with experiment across varying laser preheating temperature and power. With the semi-analytical method presented here, deterministic laser smoothing can be achieved in the densification regime to close the process loop of laser polishing. [ABSTRACT FROM AUTHOR]

Background: Various studies have indicated that stress hyperglycemia ratio (SHR) can reflect true acute hyperglycemic status and is associated with poor outcomes in patients with acute coronary syndrome (ACS). However, data on dialysis patients with ACS are limited. The Global Registry of Acute Coronary Events (GRACE) risk score is a well-validated risk prediction tool for ACS patients, yet it underestimates the risk of major events in patients receiving dialysis. This study aimed to evaluate the association between SHR and adverse cardiovascular events in dialysis patients with ACS and explore the potential incremental prognostic value of incorporating SHR into the GRACE risk score. Methods: This study enrolled 714 dialysis patients with ACS from January 2015 to June 2021 at 30 tertiary medical centers in China. Patients were stratified into three groups based on the tertiles of SHR. The primary outcome was major adverse cardiovascular events (MACE), and the secondary outcomes were all-cause mortality and cardiovascular mortality. Results: After a median follow-up of 20.9 months, 345 (48.3%) MACE and 280 (39.2%) all-cause mortality occurred, comprising 205 cases of cardiovascular death. When the highest SHR tertile was compared to the second SHR tertile, a significantly increased risk of MACE (adjusted hazard ratio, 1.92; 95% CI, 1.48–2.49), all-cause mortality (adjusted hazard ratio, 2.19; 95% CI, 1.64–2.93), and cardiovascular mortality (adjusted hazard ratio, 2.70; 95% CI, 1.90–3.83) was identified in the multivariable Cox regression model. A similar association was observed in both diabetic and nondiabetic patients. Further restricted cubic spline analysis identified a J-shaped association between the SHR and primary and secondary outcomes, with hazard ratios for MACE and mortality significantly increasing when SHR was > 1.08. Furthermore, adding SHR to the GRACE score led to a significant improvement in its predictive accuracy for MACE and mortality, as measured by the C-statistic, net reclassification improvement, and integrated discrimination improvement, especially for those with diabetes. Conclusions: In dialysis patients with ACS, SHR was independently associated with increased risks of MACE and mortality. Furthermore, SHR may aid in improving the predictive efficiency of the GRACE score, especially for those with diabetes. These results indicated that SHR might be a valuable tool for risk stratification and management of dialysis patients with ACS. [ABSTRACT FROM AUTHOR]

Background: The triglyceride-glucose (TyG) index has been suggested as a dependable indicator for predicting major adverse cardiovascular events (MACE) in individuals with cardiovascular conditions. Nevertheless, there is insufficient data on the predictive significance of the TyG index in end-stage renal disease (ESRD) patients with coronary artery disease (CAD). Methods: This study, conducted at multiple centers in China, included 959 patients diagnosed with dialysis and CAD from January 2015 to June 2021. Based on the TyG index, the participants were categorized into three distinct groups. The study's primary endpoint was the combination of MACE occurring within one year of follow-up, including death from any cause, non-fatal myocardial infarction, and non-fatal stroke. We assessed the association between the TyG index and MACE using Cox proportional hazard models and restricted cubic spline analysis. The TyG index value was evaluated for prediction incrementally using C-statistics, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Results: The three groups showed notable variations in the risk of MACE (16.3% in tertile 1, 23.5% in tertile 2, and 27.2% in tertile 3; log-rank P = 0.003). Following complete adjustment, patients with the highest TyG index exhibited a notably elevated risk of MACE in comparison to those in the lowest tertile (hazard ratio [HR] 1.63, 95% confidence interval [CI] 1.14–2.35, P = 0.007). Likewise, each unit increase in the TyG index correlated with a 1.37-fold higher risk of MACE (HR 1.37, 95% CI 1.13–1.66, P = 0.001). Restricted cubic spline analysis revealed a connection between the TyG index and MACE (P for nonlinearity > 0.05). Furthermore, incorporating the TyG index to the Global Registry of Acute Coronary Events risk score or baseline risk model with fully adjusted factors considerably enhanced the forecast of MACE, as demonstrated by the C-statistic, continuous NRI, and IDI. Conclusions: The TyG index might serve as a valuable and dependable indicator of MACE risk in individuals with dialysis and CAD, indicating its potential significance in enhancing risk categorization in clinical settings. [ABSTRACT FROM AUTHOR]

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 P for 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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

Exposure to Bisphenol A (BPA) has led to an increased risk of obesity and nonalcoholic fatty liver diseases (NAFLDs). However, it is as yet unclear if the damage caused by BPA is able to be repaired sufficiently after exposure has ceased. Therefore, this project aims to investigate the effects of BPA on the hepatic lipid metabolism function and its potential mechanisms in mice by comparing the BPA exposure model and the BPA exposure + cessation of drug treatment model. Herein, the male C57BL/6 mice were exposed in the dose of 50 μg/kg/day and 500 μg/kg/day BPA for 8 weeks, and then transferred to a standard chow diet for another 8 weeks to recover. Based on our previous RNA-seq study, we examined the expression patterns of some key genes. The results showed that the mice exposed to BPA manifested NAFLD features. Importantly, we also found that there was a significant expression reversion for SCD1, APOD, ANGPT4, PPARβ, LPL and G0S2 between the exposure and recovery groups, especially for SCD1 and APOD (p < 0.01). Notably, BPA could significantly decrease the level of APOD protein (p < 0.01) whereas there was an extremely significant increase after the exposure ceased. Meanwhile, APOD over-expression suppressed TG accumulation in the AML12 cells. In conclusion, the damage caused by BPA is able to be repaired by the upregulation of APOD and exposure to BPA should be carefully examined in chronic liver metabolic disorders or diseases. [ABSTRACT FROM AUTHOR]

Purpose: The pandemic of coronavirus disease 2019 (COVID-19) has highlighted the intricate relationship between underlying conditions and death. We designed this study to determine whether metformin therapy for type 2 diabetes mellitus (T2D) is associated with low in-hospital mortality in patients hospitalized for COVID-19.Materials and Methods: This was a retrospective study including patients with COVID-19 and T2D in Wuhan, from February 4th to April 11th, 2020. Patients were divided into two groups according to metformin exposure. The hazard ratio (HR) of COVID-19-related mortality and invasive mechanical ventilation was estimated using Cox regression.Results: There were 571 T2D patients among the 4330 confirmed COVID-19 patients. Of those patients, 241 received metformin therapy. The in-hospital mortality and invasive mechanical ventilation of metformin group was lower than non-metformin group. In the multivariate model, metformin use was linked to a decreased in-hospital mortality and invasive mechanical ventilation when compared with that of the control group (HR: 0.376 [95% CI 0.154– 0.922]; P = 0.033).Conclusion: Our study indicated that metformin therapy was associated with decreased death risk in COVID-19 patients with T2D. [ABSTRACT FROM AUTHOR]

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

Hong Kong is a typical global city with growing levels of substandard housing and a reduction in basic living quality. The government implemented a policy of transitional social housing (TSH) in 2018 to enhance the livelihood of low-income families. Nam Cheong 220 (NC220) is the first structural steel TSH project in Hong Kong. This study aims to evaluate the social impact and effectiveness of the project, and quantitative data were collected from individuals in three stages between 2020 and 2022. The first stage (T0) involved interviewing 106 successful applicants of NC220, followed by 91 participants in the second stage (T1) and 88 in the third stage (T2). Longitudinal analysis was implemented to scrutinize the changes observed over time, namely that the living area per capita substantially increased and housing expenses per capita decreased significantly due to residents' relocation to NC220. Housing conditions and community problems also showed significant improvement. Living satisfaction, neighbour and family relationships also demonstrated positive changes. The most difficult issue for residents was finding suitable housing after staying at NC220. The findings reveal that the first TSH in Hong Kong as an intervention significantly improved the housing circumstances of residents. The social dimensions of housing for enhancing residents' well-being is worth additional attention. [ABSTRACT FROM AUTHOR]

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

Human Phenotype Ontology (HPO)-based approaches have gained popularity in recent times as a tool for genomic diagnostics of rare diseases. However, these approaches do not make full use of the available information on disease and patient phenotypes. We present a new method called Phen2Disease, which utilizes the bidirectional maximum matching semantic similarity between two phenotype sets of patients and diseases to prioritize diseases and genes. Our comprehensive experiments have been conducted on six real data cohorts with 2051 cases (Cohort 1, n  = 384; Cohort 2, n  = 281; Cohort 3, n  = 185; Cohort 4, n  = 784; Cohort 5, n  = 208; and Cohort 6, n  = 209) and two simulated data cohorts with 1000 cases. The results of the experiments showed that Phen2Disease outperforms the three state-of-the-art methods when only phenotype information and HPO knowledge base are used, particularly in cohorts with fewer average numbers of HPO terms. We also observed that patients with higher information content scores have more specific information, leading to more accurate predictions. Moreover, Phen2Disease provides high interpretability with ranked diseases and patient HPO terms presented. Our method provides a novel approach to utilizing phenotype data for genomic diagnostics of rare diseases, with potential for clinical impact. Phen2Disease is freely available on GitHub at https://github.com/ZhuLab-Fudan/Phen2Disease. [ABSTRACT FROM AUTHOR]

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

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

Objective: Diagnosis of lupus nephritis (LN) is a complex process, which usually requires renal biopsy. We aim to establish a machine learning pipeline to help diagnosis of LN. Methods: A cohort of 681 systemic lupus erythematosus (SLE) patients without LN and 786 SLE patients with LN was established, and a total of 95 clinical, laboratory data and 17 meteorological indicators were collected. After tenfold cross-validation, the patients were divided into training set and test set. The features selected by collective feature selection method of mutual information (MI) and multisurf were used to construct the models of logistic regression, decision tree, random forest, naive Bayes, support vector machine (SVM), light gradient boosting (LGB), extreme gradient boosting (XGB), and artificial neural network (ANN), the models were compared and verified in post-analysis. Results: Collective feature selection method screens out antistreptolysin (ASO), retinol binding protein (RBP), lupus anticoagulant 1 (LA1), LA2, proteinuria and other features, and the hyperparameter optimized XGB (ROC: AUC = 0.995; PRC: AUC = 1.000, APS = 1.000; balance accuracy: 0.990) has the best performance, followed by LGB (ROC: AUC = 0.992; PRC: AUC = 0.997, APS = 0.977; balance accuracy: 0.957). The worst performance is naive Bayes model (ROC: AUC = 0.799; PRC: AUC = 0.822, APS = 0.823; balance accuracy: 0.693). In the composite feature importance bar plots, ASO, RF, Up/Ucr, and other features play important roles in LN. Conclusion: We developed and validated a new and simple machine learning pathway for diagnosis of LN, especially the XGB model based on ASO, LA1, LA2, proteinuria, and other features screened out by collective feature selection. [ABSTRACT FROM AUTHOR]

Immunoglobulin (IgG) glycosylation affects the effector functions of IgG in a myriad of biological processes and has been closely associated with numerous autoimmune diseases, including systemic lupus erythematosus (SLE), thus underlining the pathogenic role of glycosylation aberration in autoimmunity. This study aims to explore the relationship between IgG sialylation patterns and lupus pregnancy. Relative to that in serum samples from the control cohort, IgG sialylation level was aberrantly downregulated in serum samples from the SLE cohort at four stages (from preconception to the third trimester of pregnancy) and was significantly associated with lupus activity and fetal loss during lupus pregnancy. The type I interferon signature of pregnant patients with SLE was negatively correlated with the level of IgG sialylation. The lack of sialylation dampened the ability of IgG to suppress the functions of plasmacytoid dendritic cells (pDCs). RNA-seq analysis further revealed that the expression of genes associated with the spleen tyrosine kinase (SYK) signaling pathway significantly differed between IgG- and deSia-IgG-treated pDCs. This finding was confirmed by the attenuation of the ability to phosphorylate SYK and BLNK in deSia-IgG. Finally, the coculture of pDCs isolated from pregnant patients with SLE with IgG/deSia-IgG demonstrated the sialylation-dependent anti-inflammatory function of IgG. Our findings suggested that IgG influences lupus activity through regulating pDCs function via the modulation of the SYK pathway in a sialic acid-dependent manner. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to explore the association between the triglyceride glucose index (TyG) and the risk of in-hospital and one-year mortality in patients with chronic kidney disease (CKD) and cardiovascular disease (CAD) admitted to the intensive care unit (ICU). Methods: The data for the study were taken from the Medical Information Mart for Intensive Care-IV database which contained over 50,000 ICU admissions from 2008 to 2019. The Boruta algorithm was used for feature selection. The study used univariable and multivariable logistic regression analysis, Cox regression analysis, and 3-knotted multivariate restricted cubic spline regression to evaluate the association between the TyG index and mortality risk. Results: After applying inclusion and exclusion criteria, 639 CKD patients with CAD were included in the study with a median TyG index of 9.1 [8.6,9.5]. The TyG index was nonlinearly associated with in-hospital and one-year mortality risk in populations within the specified range. Conclusion: This study shows that TyG is a predictor of one-year mortality and in-hospital mortality in ICU patients with CAD and CKD and inform the development of new interventions to improve outcomes. In the high-risk group, TyG might be a valuable tool for risk categorization and management. Further research is required to confirm these results and identify the mechanisms behind the link between TyG and mortality in CAD and CKD patients. [ABSTRACT FROM AUTHOR]

A number of studies have attempted to reduce the effect of observation errors on Global Navigation Satellite Systems positioning through empirical error models. However, due to the complex spatiotemporal characteristics of observation errors, the effects of these errors cannot be eliminated, resulting in the unmodeled error in the positioning results. Although many studies have been carried out on unmodeled error mitigation, most of which only focus on positioning model optimization and fail to make use of historical observation data. We explore the relationship between unmodeled error and observation features and develop a new data-driven approach based on machine learning. Historical observations of a specific station are used to predict the unmodeled error of a positioning model. Time–frequency analysis is used to evaluate the prediction results. The feasibility of applying the method to the precise point positioning (PPP) kinematic positioning is verified by using IGS station data. It is clear from the findings that the data-driven model can effectively predict the unmodeled errors in GNSS positioning, especially in low-frequency components. In addition, the influencing factors of the method are explored in detail and the relevant settings are recommended. [ABSTRACT FROM AUTHOR]

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