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Abstract To analyze the risk factors of secondary Central nervous system infections (CNSIs) after craniotomy, and to establish an individualized predictive model for CNSIs risk. The independent risk factors were screened by univariate and multivariate logistic regression analysis. Logistic regression, naive bayes, random forest, light GBM and adaboost algorithms were used to establish predictive models for secondary CNSIs after craniotomy. The predictive model based on the Adaboost algorithm demonstrated superior prediction performance compared to the other four models. Under 5-fold cross validation, the accuracy was 0.80, the precision was 0.69, the recall was 0.85, the F1-score was 0.76, the area under the ROC curve was 0.897,and the average precision was 0.880. The top 5 variables of importance in Adaboost model were operation time, indwelling time of lumbar drainage tube, indwelling lumbar drainage tube during operation, indwelling epidural drainage tube during operation, and GCS score. In addition, Adaboost model with the best prediction performance was used for clinical verification, and the prediction results were compared with the actual occurrence of CNSIs after surgery. The results showed that the accuracy of Adaboost model in predicting CNSIs was 60%, the accuracy of Adaboost model in predicting non-CNSIS was 92%, and the overall prediction accuracy was 76%.

Abstract Accumulating evidence has revealed the gut bacteria dysbiosis and brain hippocampal functional and structural alterations in major depressive disorder (MDD). However, the potential relationship between the gut microbiota and hippocampal function alterations in patients with MDD is still very limited. Data of resting-state functional magnetic resonance imaging were acquired from 44 unmedicated MDD patients and 42 demographically matched healthy controls (HCs). Severn pairs of hippocampus subregions (the bilateral cornu ammonis [CA1-CA3], dentate gyrus (DG), entorhinal cortex, hippocampal–amygdaloid transition area, and subiculum) were selected as the seeds in the functional connectivity (FC) analysis. Additionally, fecal samples of participants were collected and 16S rDNA amplicon sequencing was used to identify the altered relative abundance of gut microbiota. Then, association analysis was conducted to investigate the potential relationships between the abnormal hippocampal subregions FC and microbiome features. Also, the altered hippocampal subregion FC values and gut microbiota levels were used as features separately or together in the support vector machine models distinguishing the MDD patients and HCs. Compared with HCs, patients with MDD exhibited increased FC between the left hippocampus (CA2, CA3 and DG) and right hippocampus (CA2 and CA3), and decreased FC between the right hippocampal CA3 and bilateral posterior cingulate cortex. In addition, we found that the level of proinflammatory bacteria (i.e., Enterobacteriaceae) was significantly increased, whereas the level of short-chain fatty acids producing-bacteria (i.e., Prevotellaceae, Agathobacter and Clostridium) were significantly decreased in MDD patients. Furthermore, FC values of the left hippocampal CA3- right hippocampus (CA2 and CA3) was positively correlated with the relative abundance of Enterobacteriaceae in patients with MDD. Moreover, altered hippocampal FC patterns and gut microbiota level were considered in combination, the best discrimination was obtained (AUC = 0.92). These findings may provide insights into the potential role of gut microbiota in the underlying neuropathology of MDD patients.

Objectives: Peritoneal dialysis (PD) access damage is an uncommon complication of PD. This study aimed to describe the characteristics, management and outcomes of PD access damage.Methods: This retrospective study included patients who suffered from PD access damage between January 2018 and January 2024 at the PD Center of West China Hospital. Patient characteristics and access damage information were collected from medical records.Results: A total of 128 PD patients without PD access damage were included in the control group. A total of 45 patients (51% male; aged 58 ± 14 years) suffered from 49 cases of PD access damage. Multivariate logistic analysis revealed that previous peritonitis [odds ratio (OR) 3.93; 95% confidence interval (CI) 1.56 to 9.94] and assisted PD (OR 4.20; 95% CI 1.25 to 14.12) were risk factors, while catheter belt use (OR 0.16; 95% CI 0.06 to 0.44) and training frequency per year (0.34; 95% CI 0.19 to 0.64) were protective factors against PD access damage. Managements included cutting and repairing (N = 24), transfer set replacement (N = 11), catheter removal (N = 9) and catheter replacement (N = 4). Thirty-nine patients continued with PD after access repair and were followed up for a median of 35 months. The repaired access functioned well during follow-up.Conclusions: In conclusion, to avoid PD access damage, catheter belt and routine retraining are recommended. Once PD access damage is identified, patients should clamp the catheter, take prophylactic antibiotics and resort to the treatment team. The treatment team should evaluate PD access and handle it according to a clinical protocol.

An oxidising and substituting one-pot reaction strategy has been developed to synthesise dihydromyricetin derivatives with the aim of enhancing the inhibitory activity of dihydromyricetin against SARS-CoV-2. Different ω-methoxy-ω-oxeylkyl was introduced in C7-OH site and yielded eight analogs, all of them showed good inhibitory activity against SARS-CoV-2 3CLpro with IC50 values ranging from 0.72 to 2.36 μM. In the Vero E6-cell, compound 3 has a good activity of anti-SARS-CoV-2 virus (Omicron virus BA.5) in the prevention model, with an EC50 of 15.84 μM, and so do compound 10 in the therapeutic model, with an EC50 of 11.52 μM. The results suggest that the introduction of long chain ω-oxeylkyl at C7-OH facilitate the inhibition of viral replication in the therapeutic model, which is consistent with the binding energies predicted from molecular docking conclusions. It implies that dihydromyricetin derivatives have the potential to become effective inhibitors of SARS-CoV-2 Omicron and other viruses.

BackgroundSuicidal behavior including suicidal ideation (SI) and suicide attempts (SA) is a common clinical feature of adolescent patients with major depressive disorders (MDD). We hypothesized that differences in functional connectivity density (FCD) exist between adolescent patients with SA and SI, and aimed to investigate the different suicidal behaviors in adolescents patients with MDD17.Methods37 MDD adolescents with SA, 34 MDD adolescents with SI, 20 MDD adolescents without SA and SI (non-suicidal group), and 20 adolescents healthy controls (HC) were enrolled in this study. All participants were scanned using functional magnetic resonance imaging (fMRI) to evaluated the FCD. Between-group differences of all variables were analyzed. The relationships between FCD values and clinical scale scores were also analyzed.ResultsThe FCD of the left inferior occipital gyrus in the SI group was higher than those in the other groups. The FCD in the SA group was higher than that in the control group. The FCD of the right dorsolateral superior frontal gyrus in the SI group was lower than that in the other three groups. The FCD values of the left precentral gyrus in the SI group were higher than those in the other three groups. The left inferior occipital gyrus FCD positively correlated with the suicide factor score of Hamilton Depression Scale (HAMD), and the right dorsolateral superior frontal gyrus negatively correlated with the HAMD suicide factor score but not with the HAMD total score.ConclusionChanges in FCD in adolescent patients with depression and SI can reflect changes in functional connections in the brain.

IntroductionChina’s manufacturing sector is a cornerstone of its industrial system. However, some parts of China are dominated by heavy chemicals, which leads to severe environmental pollution. The emergence of green finance (GF) can influence social capital to gradually withdraw from companies that emit pollution and increase investment in environmentally friendly ones.MethodsThis paper selects the data related to GF and the manufacturing industry (MI) from 2011 to 2020 by exploring the effect of GF on the transformation and upgrading of manufacturing industries (MIU) through literature analysis and the Spatial Durbin model.ResultsThe results demonstrate that GF positively influences the promotion of MIU, whereas MIU has a good spatial spillover effect. The results of this regression remain robust after a series of tests.DiscussionThis research suggests that the government and enterprises should pay attention to GF and encourage more enterprises to take the initiative to adjust the industrial direction and achieve a clean upgrade in manufacturing.

Epithelioid hemangioma (EHE) is a rarely malignant tumor originating from the vascular endothelium. Morphological manifestations and immunohistochemical staining results are key to diagnosing EHE. Herein, we present a case of cutaneous involment in a recurrence of EHE. A 75-year-old woman presented with a month-long history of persistent erythematous plaque and pain in the left shoulder. Skin biopsy specimen revealed epithelioid tumor cells containing abundant eosinophilic cytoplasm. Immunohistochemical staining confirmed a recurrence of EHE involving the skin. Subsequently, recombinant human endostatin was administered. At the 10-day follow-up, the cutaneous plaque had improved, and the pain had resolved. When presenting as a local painful erythematous plaque, the possibility of skin involvement in a malignant tumor should be considered. Early diagnosis and early systemic therapy have an important impact on the overall survival of patients with EHE.

SARS-CoV-2 spike protein (SARS-2-S) induced cell-cell fusion in uninfected cells may occur in long COVID-19 syndrome, as circulating SARS-2-S or extracellular vesicles containing SARS-2-S (S-EVs) were found to be prevalent in post-acute sequelae of COVID-19 (PASC) for up to 12 months after diagnosis. Although isolated recombinant SARS-2-S protein has been shown to increase the SASP in senescent ACE2-expressing cells, the direct linkage of SARS-2-S syncytia with senescence in the absence of virus infection and the degree to which SARS-2-S syncytia affect pathology in the setting of cardiac dysfunction are unknown. Here, we found that the senescent outcome of SARS-2-S induced syncytia exacerbated heart failure progression. We first demonstrated that syncytium formation in cells expressing SARS-2-S delivered by DNA plasmid or LNP-mRNA exhibits a senescence-like phenotype. Extracellular vesicles containing SARS-2-S (S-EVs) also confer a potent ability to form senescent syncytia without de novo synthesis of SARS-2-S. However, it is important to note that currently approved COVID-19 mRNA vaccines do not induce syncytium formation or cellular senescence. Mechanistically, SARS-2-S syncytia provoke the formation of functional MAVS aggregates, which regulate the senescence fate of SARS-2-S syncytia by TNFα. We further demonstrate that senescent SARS-2-S syncytia exhibit shrinked morphology, leading to the activation of WNK1 and impaired cardiac metabolism. In pre-existing heart failure mice, the WNK1 inhibitor WNK463, anti-syncytial drug niclosamide, and senolytic dasatinib protect the heart from exacerbated heart failure triggered by SARS-2-S. Our findings thus suggest a potential mechanism for COVID-19-mediated cardiac pathology and recommend the application of WNK1 inhibitor for therapy especially in individuals with post-acute sequelae of COVID-19.

Abstract Lithium-ion batteries play a crucial role in decarbonizing transportation and power grids, but their reliance on high-cost, earth-scarce cobalt in the commonly employed high-energy layered Li(NiMnCo)O2 cathodes raises supply-chain and sustainability concerns. Despite numerous attempts to address this challenge, eliminating Co from Li(NiMnCo)O2 remains elusive, as doing so detrimentally affects its layering and cycling stability. Here, we report on the rational stoichiometry control in synthesizing Li-deficient composite-structured LiNi0.95Mn0.05O2, comprising intergrown layered and rocksalt phases, which outperforms traditional layered counterparts. Through multiscale-correlated experimental characterization and computational modeling on the calcination process, we unveil the role of Li-deficiency in suppressing the rocksalt-to-layered phase transformation and crystal growth, leading to small-sized composites with the desired low anisotropic lattice expansion/contraction during charging and discharging. As a consequence, Li-deficient LiNi0.95Mn0.05O2 delivers 90% first-cycle Coulombic efficiency, 90% capacity retention, and close-to-zero voltage fade for 100 deep cycles, showing its potential as a Co-free cathode for sustainable Li-ion batteries.

Abstract Li metal batteries using Li metal as negative electrode and LiNi1-x-yMnxCoyO2 as positive electrode represent the next generation high-energy batteries. A major challenge facing these batteries is finding electrolytes capable of forming good interphases. Conventionally, electrolyte is fluorinated to generate anion-derived LiF-rich interphases. However, their low ionic conductivities forbid fast-charging. Here, we use CsNO3 as a dual-functional additive to form stable interphases on both electrodes. Such strategy allows the use of 1,2-dimethoxyethane as the single solvent, promising superior ion transport and fast charging. LiNi1-x-yMnxCoyO2 is protected by the nitrate-derived species. On the Li metal side, large Cs+ has weak interactions with the solvent, leading to presence of anions in the solvation sheath and an anion-derived interphase. The interphase is surprisingly dominated by cesium bis(fluorosulfonyl)imide, a component not reported before. Its presence suggests that Cs+ is doing more than just electrostatic shielding as commonly believed. The interphase is free of LiF but still promises high performance as cells with high LiNi0.8Mn0.1Co0.1O2 loading (21 mg/cm2) and low N/P ratio (~2) can be cycled at 2C (~8 mA/cm2) with above 80% capacity retention after 200 cycles. These results suggest the role of LiF and Cs-containing additives need to be revisited.

Abstract Car-following is a control process in which a following vehicle adjusts its acceleration to keep a safe distance from the lead vehicle. Recently, there has been a booming of data-driven models that enable more accurate modeling of car-following through real-world driving datasets. Although there are several public datasets available, their formats are not always consistent, making it challenging to determine the state-of-the-art models and how well a new model performs compared to existing ones. To address this gap and promote the development of microscopic traffic flow modeling, we establish the first public benchmark dataset for car-following behavior modeling. This benchmark consists of more than 80 K car-following events extracted from five public driving datasets under the same criteria. To give an overview of current progress in car-following modeling, we implemented and tested representative baseline models within the benchmark. The established benchmark provides researchers with consistent data formats and metrics for cross-comparing different car-following models, coming with open datasets and codes.

Gut microbiome plays an important role in host's development and reproduction. Lotus-fish co-culture (LFC) is a popular integrated agriculture–aquaculture farming system in China. However, there is still a relative dearth of information on how changes of aquaculture modes will affect the fish gut microbiome. In the present study, metagenomic sequencing was used to compare gut bacteria of the hybrid fish Hefang crucian carp (Carassius cuuieri ♀ × C. auratus var. red ♂) cultured in LFC and intensive pond culture (IPC) systems. The results indicated that aquaculture modes exerted great influences on the fish gut bacterial community. A significantly higher gut bacterial diversity was found in LFC than that in IPC (P

BackgroundNo consistent conclusion has been reached regarding the attentional bias characteristics of adolescents with major depressive disorders (MDD), and unexamined co-occurring anxiety distress may contribute to this inconsistency.MethodsWe enrolled 50 MDD adolescents with anxiety distress, 47 MDD adolescents without anxiety distress and 48 healthy adolescents. We measured attentional bias using a point-probe paradigm during a negative-neutral emotional face task. Reaction time, correct response rate and attentional bias value were measured.ResultsMDD adolescents did not show a negative attentional bias; MDD adolescents with anxiety distress exhibited longer reaction time for negative and neutral stimuli, lower correct response rate for negative stimuli. Hamilton Anxiety Scale scores were positively correlated with reaction time, negatively correlated with correct response rate, and not significantly correlated with attentional bias value.LimitationsThe cross-sectional design hinders causal attribution, and positive emotional faces were not included in our paradigm.ConclusionNegative attentional bias is not a stable cognitive trait in adolescents with MDD, and avoidance or difficulty in disengaging attention from negative emotional stimuli may be the attentional bias characteristic of MDD adolescents with anxiety distress.

In order to measure wheat yield and wheat spike phenotypes, the grain number of wheat spikes is counted manually at present, but acquiring the grain number of wheat spikes is laborious and time-consuming. Counting the grain number of wheat spikes with an image processing method is promising, yet the application of this method is flawed due to its low accuracy. In this work, images of wheat spikes were collected and processed with technical procedures, including image cropping, image graying, histogram equalization, image binarization, eroding operation, removing small objects, filling image holes, revolving vertical spikes, cutting off stems, and removing stems. Wheat stems in binary images were eliminated by the sum pixels method, and the morphological characteristic parameters of the image areas of wheat spikes and lengths of wheat spike axes were calculated. Mathematical models relating the image areas of wheat spikes and lengths of the wheat spike axes to the grain number were established, and the mathematical models were verified. The results showed that the characteristic parameters of the image areas of wheat spikes and the lengths of the wheat spike axes for the spike images were linear relative to the grain number, and the maximum determination coefficients R2 were 0.9336 and 0.9012, respectively. The maximum determination coefficients R2 for the practical and predicted grain numbers were 0.9552 and 0.9369, respectively, and the minimum average absolute error was 2.3, while the average relative error for the mathematical models was 5.65%. The mathematical models relating the image areas of wheat spikes and the lengths of the wheat spike axes to the grain number were practical and accurate, and the mathematical model comparing the image area of wheat spikes and the grain number was superior to that comparing the length of the wheat spike axis and the grain number. The grain number of wheat spikes could be acquired accurately and quickly by the image processing method extracting the characteristic parameters of wheat spikes.

This study explores the effectiveness of an integrated anaerobic membrane bioreactor (AnMBR) coupled with an anoxic/oxic membrane bioreactor (A/O MBR) for the treatment of natural rubber industry wastewater with high sulfate, ammonia, and complex organic contents. This study was conducted at the lab-scale over a duration of 225 days to thoroughly investigate the efficiency and sustainability of the proposed treatment method. With a hydraulic retention time of 6 days for the total system, COD reductions were over 98%, which reduced the influent from 22,158 ± 2859 mg/L to 118 ± 74 mg/L of the effluent. The system demonstrates average NH3-N, TN, and total phosphorus (TP) removal efficiencies of 72.9 ± 5.7, 72.8 ± 5.6, and 71.3 ± 9.9, respectively. Despite an average whole biological system removal of 50.6%, the anaerobic reactor eliminated 44.9% of the raw WW sulfate. Analyses of membrane fouling revealed that organic fouling was more pronounced in the anaerobic membrane, whereas aerobic membrane fouling displayed varied profiles due to differential microbial and oxidative activities. Key bacterial genera, such as Desulfobacterota in the anaerobic stage and nitrifiers in the aerobic stage, are identified as instrumental in the biological processes. The microbial profile reveals a shift from methanogenesis to sulfide-driven autotrophic denitrification and sulfammox, with evidence of an active denitrification pathway in anaerobic/anoxic conditions. The system showcases its potential for industrial application, underpinning environmental sustainability through improved wastewater management.

The wavefront reconstruction is a crucial step in determining the performance of wavefront detection instruments. The wavefront reconstruction algorithm is primarily evaluated in three dimensions: accuracy, speed, and noise immunity. In this paper, we propose a hybrid zonal reconstruction algorithm that introduces slope and curvature information in the diagonal, anti-diagonal, horizontal, and vertical directions by dividing the neighbor sampling points into subregions in groups of four. By canceling the same parameters in integration equations, an algorithm using multi-directional slope–curvature information is achieved with only two sets of integration equations in each subregion, reducing the processing time. Simulation experiments show that the relative root-mean-square reconstruction error of this algorithm is improved by about 4 orders of magnitude compared with existing algorithms that use multi-directional slope information or slope–curvature information alone. Compared with the hybrid multi-directional slope–curvature algorithm, the proposed algorithm can reduce computation time by about 50% as well as provide better noise immunity and reconstruction accuracy. Finally, the validity of the proposed algorithm is verified by the null test experiment.

Abstract Solid‐state metal dealloying (SSMD) is a promising method for fabricating nanoscale metallic composites and nanoporous metals across a range of materials. Thin‐film SSMD is particularly attractive due to its ability to create fine features via solid‐state interfacial reactions within a thin‐film geometry, which can be integrated into devices for various applications. This work examines a new dealloying couple, namely the Nb–Al alloy with the dealloying agent Sc, as previously predicted in the machine‐learning (ML) models. Prior ML predictions aimed to guide the design of nanoarchitectured materials through dealloying, relying on intuition‐driven discovery within a large parameter space. However, this work reveals that at the nanoscale, the involvement of oxygen in thin film processing may instead drive the dealloying process, resulting in the formation of bicontinuous nanostructures similar to those formed by metal‐agent dealloying. The phase evolution, as well as chemical and morphological changes, are closely analyzed using a combination of X‐ray absorption spectroscopy, diffraction, and scanning transmission electron microscopy to understand the mechanisms behind nanostructure formation. The findings suggest a potential pathway for utilizing oxygen to drive the formation of bicontinuous metal–metal oxide nanocomposites, paving the way for further development of functional nanoporous materials in diverse fields.

Calciphylaxis is a rare and life-threatening condition in patients with end-stage kidney disease (ESKD). In this case report, we reported a 72-year-old female who had undergone aortic and mitral mechanical valve replacement 22 years ago due to rheumatic aortic and mitral stenosis. Following the valve replacement, she initiated warfarin treatment. Five years ago, she received a diagnosis of uremia and has since been undergoing regular hemodialysis. Ten months prior to her current admission, she experienced excruciating pain and was diagnosed with calciphylaxis. Additionally, an electrocardiogram revealed atrial fibrillation, while echocardiography indicated that the aortic and mitral mechanical valves were appropriately positioned, with normal perivalvular surroundings and good valve leaflet activity. No noticeable thrombosis was observed in the left atrium or left atrial appendage. Color Doppler imaging showed moderate stenosis in the lower extremity arteries, with no venous thromboembolism present. Extensive eggshell-like calcification within the arterial media was detected. The patient was managed with regular hemodialysis, symptomatic treatments (including anticoagulation and analgesia), and sodium thiosulfate. Unfortunately, symptomatic management provided limited relief, and during the one-month follow-up period, the patient passed away due to septic shock. Currently, there is insufficient conclusive evidence regarding alternative influential anticoagulants or appropriate prosthetic valve selection. For individuals with ESKD receiving maintenance hemodialysis, early identification, diagnosis, and treatment of calciphylaxis are of paramount importance.

Abstract Introduction Axial length (AL) elongation in myopia is considered irreversible. We aimed to systemically report unexpected AL shortening observed in a randomized clinical trial (RCT) after repeated low-level red-light (RLRL) therapy. Methods This is a post hoc analysis of a multicenter, single-masked RCT. Two hundred sixty-four myopic children aged 8–13 years allocated to RLRL treatment (intervention group) or a single vision spectacle (SVS, control group) were included. AL was measured using an IOL-master 500 at baseline, 1-, 3-, 6-, and 12-month follow-up visits. AL shortening was defined as AL reduction from baseline to follow-up visits at three cutoffs: > 0.05 mm, > 0.10 mm, and > 0.20 mm. Frequency of AL shortening at different cutoffs was calculated. Analysis was done with intent to treat (ITT). Results At 12-months follow up, frequency of AL shortening > 0.05 mm was 26/119 (21.85%) and 2/145 (1.38%) for the RLRL group versus the control group, respectively. The frequency was 18/119 (15.13%) versus 0/145 (0%) for AL shortening > 0.10 mm, and 7/119 (5.88%) versus 0/145 (0%), for AL shortening > 0.20 mm, respectively (p 0.05 mm AL shortening following 12 months of RLRL therapy, whereas AL shortening rarely occurred among controls. Trial Registration ClinicalTrials.gov (NCT04073238).

Abstract Autism spectrum disorder (ASD) is a complex behavioral disorder diagnosed by social interaction difficulties, restricted verbal communication, and repetitive behaviors. Fecal microbiota transplantation (FMT) is a safe and efficient strategy to adjust gut microbiota dysbiosis and improve ASD-related behavioral symptoms, but its regulatory mechanism is unknown. The impact of the microbiota and its functions on ASD development is urgently being investigated to develop new therapeutic strategies for ASD. We reconstituted the gut microbiota of a valproic acid (VPA)-induced autism mouse model through FMT and found that ASD is in part driven by specific gut dysbiosis and metabolite changes that are involved in the signaling of serotonergic synapse and glutamatergic synapse pathways, which might be associated with behavioral changes. Further analysis of the microbiota showed a profound decrease in the genera Bacteroides and Odoribacter, both of which likely contributed to the regulation of serotonergic and glutamatergic synapse metabolism in mice. The engraftment of Turicibacter and Alistipes was also positively correlated with the improvement in behavior after FMT. Our results suggested that successful transfer of the gut microbiota from healthy donors to ASD mice was sufficient to improve ASD-related behaviors. Modulation of gut dysbiosis by FMT could be an effective approach to improve ASD-related behaviors in patients.

Abstract Porous materials with high specific surface area, high porosity, and high electrical conductivity are promising materials for functional applications, including catalysis, sensing, and energy storage. Molten salt dealloying was recently demonstrated in microwires as an alternative method to fabricate porous structures. The method takes advantage of the selective dissolution process introduced by impurities often observed in molten salt corrosion. This work further investigates molten salt dealloying in bulk Ni–20Cr alloy in both KCl–MgCl2 and KCl–NaCl salts at 700 ℃, using scanning electron microscopy, energy dispersive spectroscopy, and X-ray diffraction (XRD), as well as synchrotron X-ray nano-tomography. Micro-sized pores with irregular shapes and sizes ranging from sub-micron to several microns and ligaments formed during the process, while the molten salt dealloying was found to progress several microns into the bulk materials within 1–16 h, a relatively short reaction time, enhancing the practicality of using the method for synthesis. The ligament size increased from ~ 0.7 μm to ~ 1.3 μm in KCl–MgCl2 from 1 to 16 h due to coarsening, while remaining ~ 0.4 μm in KCl–NaCl during 16 h of exposure. The XRD analysis shows that the corrosion occurred primarily near the surface of the bulk sample, and Cr2O3 was identified as a corrosion product when the reaction was conducted in an air environment (controlled amount sealed in capillaries); thus surface oxides are likely to slow the morphological coarsening rate by hindering the surface diffusion in the dealloyed structure. 3D-connected pores and grain boundary corrosion were visualized by synchrotron X-ray nano-tomography. This study provides insights into the morphological and chemical evolution of molten salt dealloying in bulk materials, with a connection to molten salt corrosion concerns in the design of next-generation nuclear and solar energy power plants.

Context Osthole shows antitumor effects in various tumours. Studies describing the effect of osthole on retinoblastoma (RB) are rare. Objective This study investigates the antitumor activity of osthole on RB. Materials and methods RB cells were treated with different concentrations of osthole and then subjected to cell viability, colony formation, apoptosis, and western blot assays. The expression of hsa_circ_0007534 in RB tissues was determined by qRT-PCR. Hsa_circ_0007534 overexpression plasmid (oe-circ_0007534), miR-214-3p mimics and negative controls were transfected into RB cells to investigate cell viability. Athymic nude mice were injected with Y-79 cells to establish subcutaneous RB models. These mice were treated with osthole (0.5 mmol/kg) or corn oil for 36 days. Tumour tissues were collected for further analysis. Results Osthole inhibited cell viability of RB cells with an IC50 of 200 μM for 24 h treatment and 120 μM for 48 h treatment, respectively. Hsa_circ_0007534 was increased significantly in RB tissues as compared to the matched nontumor tissues (p

Objective To develop and validate an ultrasonic radiomics model for predicting the recurrence and differentiation of hepatocellular carcinoma (HCC). Convolutional neural network (CNN) ResNet 18 and Pyradiomics were used to analyze gray-scale-ultrasonic images to predict the prognosis and degree of differentiation of HCC.Methods This retrospective study enrolled 513 patients with HCC who underwent preoperative grayscale-ultrasonic imaging, and their clinical characteristics were observed. Patients were randomly divided into training (n = 413) and validation (n = 100) cohorts. CNN ResNet 18 and Pyradiomics were used to analyze ultrasonic images of HCC and peritumoral images to develop a prognostic and differentiation model. Clinical characteristics were integrated into the radiomics model and patients were stratified into high- and low-risk groups. The predictive effect was evaluated using the C-index and receiver operating characteristic (ROC) curve.Results The model combined with ResNet 18 and clinical characteristics achieved a good predictive ability. The C-indices of early recurrence (ER), late recurrence (LR), and recurrence-free survival (RFS) were 0.695 (0.561–0.789), 0.715 (0.623–0.800) and 0.721 (0.647–0.795), respectively, in the validation cohort, which was superior to the clinical model and ultrasonic semantic model. The model could stratify patients into high- and low-risk groups, which showed significant differences (p

Nanoporous metals produced by metal agent dealloying are attractive for multiple applications. Here, a machine learning-augmented framework is reported for predicting, synthesizing and characterizing ternary systems for dealloying.

Here the authors report a single arm pilot trial to investigate combined spinal neuromodulation and activity-based neurorehabilitation therapy on voluntary sensory-motor function in children with cerebral palsy.

Sickle cell disease (SCD) is a hereditary hemoglobinopathy characterized by painful vaso-occlusive crises (VOC) and chronic hemolysis. The mononuclear phagocyte system is pivotal to SCD pathophysiology, but the mechanisms governing monocyte/macrophage differentiation remain unknown. This study examined the influence of hemolysis on circulating monocyte trajectories in SCD. We discovered that hemolysis stimulated CSF-1 production, partly by endothelial cells via Nrf2, promoting classical monocyte (CMo) differentiation into blood patrolling monocytes (PMo) in SCD mice. However, hemolysis also upregulated CCL-2 through IFN-I, inducing CMo transmigration and differentiation into tissue monocyte–derived macrophages. Blocking CMo transmigration by anti–P selectin antibody in SCD mice increased circulating PMo, corroborating that CMo-to–tissue macrophage differentiation occurs at the expense of CMo-to–blood PMo differentiation. We observed a positive correlation between plasma CSF-1/CCL-2 ratios and blood PMo levels in patients with SCD, underscoring the clinical significance of these two opposing factors in monocyte differentiation. Combined treatment with CSF-1 and anti–P selectin antibody more effectively increased PMo numbers and reduced stasis compared with single-agent therapies in SCD mice. Altogether, these data indicate that monocyte fates are regulated by the balance between two heme pathways, Nrf2/CSF-1 and IFN-I/CCL-2, and suggest that the CSF-1/CCL-2 ratio may present a diagnostic and therapeutic target in SCD.

ObjectiveThis study aimed to investigate the clinical application effect of an augmented reality (AR) plasticity model on the postoperative visual function recovery of children with concomitant exotropia.MethodsBetween September 2019 and October 2021, 28 patients with concomitant exotropia who visited Shenzhen Children’s Hospital (9 male and 19 female) were enrolled in this study. The average age of the patients was 6.4 ± 1.8 years. Postoperative rehabilitation training was conducted using a personalized AR binocular visual perception plasticity model developed based on the patient’s examination results. After 1 month, 3 months, and 6 months of training, the patients returned to the hospital for examinations of perceptual eye position, static zero-order stereopsis, dynamic first-order fine stereopsis, and dynamic second-order coarse stereopsis to compare the changes in eye position control and stereovision function.ResultsAfter 6 months of eye position training, the horizontal perception eye position of the 28 patients was significantly lower than that before training. The difference in eye position at the first and third months compared with that before training was not statistically significant (1st month: z = −2.255, p = 0.024 > 0.017; 3rd month: z = −2.277, p = 0.023 > 0.017; 6th month: z = −3.051, p = 0.002 0.017; 3rd month: z = −1.189, p = 0.234 > 0.017; 6th month: z = −2.225, p = 0.026 > 0.017). The difference in 0.8-m static zero-order stereopsis before and after training was not statistically significant (1st month: z = −2.111, p = 0.035 > 0.017; 3rd month: z = −1.097, p = 0.273 > 0.017; 6th month: z = −1.653, p = 0.098 > 0.017). The 1.5-m static zero-order stereopsis was improved after 1 month, 3 months, and 6 months of training compared with that before training (1st month: z = −3.134, p = 0.002

Osteoporosis (OP), a common systemic bone metabolism disease with a high incidence rate, is a serious health risk factor. Osteogenic differentiation balance is regulated by bone marrow mesenchymal stem cells (BMSCs) and plays a key role in OP occurrence and progression. Although, LIM homeobox 8 (Lhx8) has been identified to affect BMSCs osteogenic differentiation, its roles in OP and the associated mechanism remains unclear. Here, we aimed to elucidate the role and mechanism of Lhx8 in the osteogenic differentiation of BMSCs. BMSCs isolated from wild type and OP Sprague–Dawley rats were cultured and confirmed via flow cytometry and microscopy. Based on dual-luciferase reporter assay, BMSCs were transfected with miR-142-5p mimics and miR-NC (negative control). Real-time quantitative reverse transcription polymerase chain reaction and Western blot analyses were performed to determine the role of Lhx8 in BMSCs osteogenic differentiation. Lhx8 expression was significantly reduced in OP, whereas that of miR-142-5p, a possible Lhx8 regulator, was significantly upregulated. Dual-luciferase reporter assay demonstrated that miR-142-5p exerted a direct targeted regulatory effect on Lhx8. Moreover, miR-142-5p mimics significantly inhibited BMSCs osteogenic differentiation as well as Lhx8 expression in vitro, indicating that miR-142-5p may be involved in BMSCs osteogenic differentiation via Lhx8 expression regulation and may serve as a potential diagnostic target for OP. Overall, these findings indicated that miR-142-5p inhibits BMSCs osteogenic differentiation by suppressing Lhx8. These may serve as a foundation for further studies on OP treatment based on miR-142-5p targeting.

Summary: Amino acid (aa) metabolism is closely correlated with the pathogenesis of psoriasis; however, details on aa transportation during this process are barely known. Here, we find that SLC38A5, a sodium-dependent neutral aa transporter that counter-transports protons, is markedly upregulated in the psoriatic skin of both human patients and mouse models. SLC38A5 deficiency significantly ameliorates the pathogenesis of psoriasis, indicating a pathogenic role of SLC38A5. Surprisingly, SLC38A5 is almost exclusively expressed in dendritic cells (DCs) when analyzing the psoriatic lesion and mainly locates on the lysosome. Mechanistically, SLC38A5 potentiates lysosomal acidification, which dictates the cleavage and activation of TLR7 with ensuing production of pro-inflammatory cytokines such as interleukin-23 (IL-23) and IL-1β from DCs and eventually aggravates psoriatic inflammation. In summary, this work uncovers an auxiliary mechanism in driving lysosomal acidification, provides inspiring insights for DC biology and psoriasis etiology, and reveals SLC38A5 as a promising therapeutic target for treating psoriasis.

Summary: γδ T cells make key contributions to tissue physiology and immunosurveillance through two main functionally distinct subsets, γδ T1 and γδ T17. m6A methylation plays critical roles in controlling numerous aspects of mRNA metabolism that govern mRNA turnover, gene expression, and cellular functional specialization; however, its role in γδ T cells remains less well understood. Here, we find that m6A methylation controls the functional specification of γδ T17 vs. γδ T1 cells. Mechanistically, m6A methylation prevents the formation of endogenous double-stranded RNAs and promotes the degradation of Stat1 transcripts, which converge to prevent over-activation of STAT1 signaling and ensuing inhibition of γδ T17. Deleting Mettl3, the key enzyme in the m6A methyltransferases complex, in γδ T cells reduces interleukin-17 (IL-17) production and ameliorates γδ T17-mediated psoriasis. In summary, our work shows that METTL3-mediated m6A methylation orchestrates mRNA stability and double-stranded RNA (dsRNA) contents to equilibrate γδ T1 and γδ T17 cells.

ObjectiveTo analyze the demographic and clinical characteristics and treatment among children and adolescents with depression in different age groups of onset.Methods635 children and adolescents with depression in a hospital from January 2014 to December 2021 were collected by e-case, and grouped according to age of onset, including 115 cases in childhood 8-12, 359 cases in early adolescence 13-1 and 161 cases in late adolescence 16-18, and the general conditions, clinical characteristics, and treatment were compared between the three groups.ResultsFemales had more onset and were more likely to have psychotic symptoms in childhood, short duration and hospitalization in early adolescence increased year by year, and males had more onset and less hospitalization in late adolescence. There were no statistical differences in medication regimen, suicide, length of hospitalization, or family history between the three groups.ConclusionChildren and adolescents with depression have their unique clinical characteristics at different age of onset and need to enhance prevention and individualized treatment.

BackgroundAdolescent patients with depressive disorders commonly exhibit somatic symptoms, which have a significant negative impact on their treatment and prognosis. Despite this, specific brain imaging characteristics of these symptoms have been poorly studied.MethodsThe Hamilton Depression Rating scale (HAMD-17), Children’s Functional Somatization scale (CSI), and Toronto Alexithymia scale (TAS) were used to evaluate the clinical symptoms of adolescent depression. We analyzed the correlation between brain gray matter volume (GMV) and clinical symptoms in adolescent patients with depression and somatic symptoms.ResultsThe depression subgroups with and without functional somatic symptoms (FSS) had higher scores on the HAMD-17, CSI, and TAS than the normal control group. The group with FSS had higher HAMD-17, CSI, and TAS scores than the depression group without FSS (p

Five artemisinin bivalent ligands molecules 4a–4e were designed, synthesized, and confirmed by 1H NMR, 13C NMR, and low-resolution mass spectrometry, and the bioactivities of the target compounds were investigated against four human tumor cell lines in vitro, including BGC-823, HepG-2, MCF-7, and HCT-116. The results showed 4a, 4d, and 4e exhibited significantly tumor cell inhibitory activity compared with the artemisinin and dihydroartemisinin; compound 4e has good biological activity inhibiting BGC-823 with an IC50 value of 8.30 μmol/L. Then, the good correlations with biological results were validated by molecular docking through the established bivalent ligands multi-target model, which showed that 4e could bind well with the antitumor protein MMP-9.

IntroductionThe paralysis that occurs after a spinal cord injury, particularly during the early stages of post-lesion recovery (∼6 weeks), appears to be attributable to the inability to activate motor pools well beyond their motor threshold. In the later stages of recovery, however, the inability to perform a motor task effectively can be attributed to abnormal activation patterns among motor pools, resulting in poor coordination.MethodWe have tested this hypothesis on four adult male Rhesus monkeys (Macaca mulatta), ages 6-10 years, by recording the EMG activity levels and patterns of multiple proximal and distal muscles controlling the upper limb of the Rhesus when performing three tasks requiring different levels of skill before and up to 24 weeks after a lateral hemisection at C7. During the recovery period the animals were provided routine daily care, including access to a large exercise cage (5' × 7' × 10') and tested every 3-4 weeks for each of the three motor tasks.ResultsAt approximately 6-8 weeks the animals were able to begin to step on a treadmill, perform a spring-loaded task with the upper limb, and reaching, grasping, and eating a grape placed on a vertical stick. The predominant changes that occurred, beginning at ∼6-8 weeks of the recovery of these tasks was an elevated level of activation of most motor pools well beyond the pre-lesion level.DiscussionAs the chronic phase progressed there was a slight reduction in the EMG burst amplitudes of some muscles and less incidence of co-contraction of agonists and antagonists, probably contributing to an improved ability to selectively activate motor pools in a more effective temporal pattern. Relative to pre-lesion, however, the EMG patterns even at the initial stages of recovery of successfully performing the different motor tasks, the level of activity of most muscle remained higher. Perhaps the most important concept that emerges from these data is the large combinations of adaptive strategies in the relative level of recruitment and the timing of the peak levels of activation of different motor pools can progressively provide different stages to regain a motor skill.

Abstract Background Regorafenib belongs to a sub-group of small-molecule multi-targeted tyrosine kinase inhibitors(TKIs). In various studies with respect to the side-effect of regorafenib, drug-associated proteinuria standardly qualified to be defined as nephrotic syndrome was rarely reported as well as the relation of regorafenib with the occurrence and development of thrombotic microangiopathy (TMA). Case presentation In this case report and literature review, we presented a 62-year-old patient receiving regorafenib for metastatic colon cancer, manifesting abundant proteinuria, in which TMA was also diagnosed through renal biopsy. As far as we were concerned, this was the first reported in terms of regorafenib-induced TMA confirmed by renal biopsy. Conclusion This case indicates that regorafenib, a kind of TKIs may result in TMA, which is a rare but life-threatening complication of cancer treatment drug. Insights from this case might help physicians diagnose rare forms of TMA and adjust treatment for patients in a timely manner.

Abstract This study explored the differences in emotional memory between adolescents with and without suicidal ideation. Fifty adolescents with depression and suicidal ideation, 36 with depression but no suicidal ideation, and 41 healthy controls rated the emotional valence of positive, neutral, and negative pictures. Then, the recognition of the images was evaluated 72 h later. Adolescents with suicidal ideation reported more negative emotional valence scores for positive and neutral pictures and were significantly less likely to recognize negative pictures than were those without suicidal ideation. The performance of adolescents with suicidal ideation on the negative picture recognition test was closely related to anxiety, depression severity, and intensity of suicidal ideation. The negative bias toward neutral stimuli and cognitive impairment may be important risk factors for adolescents with suicidal ideation. Improving emotional memory via targeted management approaches may help young people with suicidal ideation.

Abstract Background An important aspect of studying evolution is to understand how new species are formed and their uniqueness is maintained. Hybridization can lead to the formation of new species through reorganization of the adaptive system and significant changes in phenotype. Interestingly, eight stable strains of 2nNCRC derived from interspecies hybridization have been established in our laboratory. To examine the phylogeographical pattern of the widely distributed genus Carassius across Eurasia and investigate the possible homoploid hybrid origin of the Carassius auratus complex lineage in light of past climatic events, the mitochondrial genome (mtDNA) and one nuclear DNA were used to reconstruct the phylogenetic relationship between the C. auratus complex and 2nNCRC and to assess how demographic history, dispersal and barriers to gene flow have led to the current distribution of the C. auratus complex. Results As expected, 2nNCRC had a very close relationship with the C. auratus complex and similar morphological characteristics to those of the C. auratus complex, which is genetically distinct from the other three species of Carassius. The estimation of divergence time and ancestral state demonstrated that the C. auratus complex possibly originated from the Yangtze River basin in China. There were seven sublineages of the C. auratus complex across Eurasia and at least four mtDNA lineages endemic to particular geographical regions in China. The primary colonization route from China to Mongolia and the Far East (Russia) occurred during the Late Pliocene, and the diversification of other sublineages of the C. auratus complex specifically coincided with the interglacial stage during the Early and Mid-Pleistocene in China. Conclusion Our results support the origin of the C. auratus complex in China, and its wide distribution across Eurasia was mainly due to natural Pleistocene dispersal and recent anthropogenic translocation. The sympatric distribution of the ancestral area for both parents of 2nNCRC and the C. auratus complex, as well as the significant changes in the structure of pharyngeal teeth and morphological characteristics between 2nNCRC and its parents, imply that homoploid hybrid speciation (HHS) for C. auratus could likely have occurred in nature. The diversification pattern indicated an independent evolutionary history of the C. auratus complex, which was not separated from the most recent common ancestor of C. carassius or C. cuvieri. Considering that the paleoclimate oscillation and the development of an eastward-flowing drainage system during the Pliocene and Pleistocene in China provided an opportunity for hybridization between divergent lineages, the formation of 2nNCRC in our laboratory could be a good candidate for explaining the HHS of C. auratus in nature.

Abstract Background Overactive bladder (OAB) affects 12 to 30% of the world’s population. The accompanying urinary urgency, frequency and incontinence can have a profound effect on quality of life, leading to depression, social isolation, avoidance of sexual activity and loss of productivity. Conservative measures such as lifestyle modification and pelvic floor physical therapy are the first line of treatment for overactive bladder. Patients who fail these may go on to take medications, undergo neuromodulation or receive injection of botulinum toxin into the bladder wall. While effective, medications have side effects and suffer from poor adherence. Neuromodulation and botulinum toxin injection are also effective but are invasive and not acceptable to some patients. Methods We have developed a novel transcutaneous spinal cord neuromodulator (SCONE™,) that delivers multifrequency electrical stimulation to the spinal cord without the need for insertion or implantation of stimulating electrodes. Previously, multifrequency transcutaneous stimulation has been demonstrated to penetrate to the spinal cord and lead to motor activation of detrusor and external urethral sphincter muscles. Here, we report on eight patients with idiopathic overactive bladder, who underwent 12 weeks of SCONE™ therapy. Results All patients reported statistically significant clinical improvement in multiple symptoms of overactive bladder, such as urinary urgency, frequency and urge incontinence. In addition, patients reported significant symptomatic improvements as captured by validated clinical surveys. Conclusion SCONE™ therapy represents the first of its kind therapy to treat symptoms of urgency, frequency and urge urinary incontinence in patients with OAB. Trial registration The study was listed on clinicaltrials.gov ( NCT03753750 ).

Abstract Aim To investigate the extent of post‐traumatic growth, and the correlation between post‐traumatic growth and self‐perceived stress, post‐traumatic growth and self‐perceived burden among CAPD patients. Design A cross‐sectional study. Methods This was a multi‐centre study including 752 patients from 44 hospitals. Self‐perceived stress, self‐perceived burden and post‐traumatic growth were measured using the post‐traumatic growth inventory (PTGI), the Chinese version of the perceived stress questionnaire (CPSQ) and the self‐perceived burden scale (SPBS). A multiple stepwise regression analysis was fit with the total PTGI score as the outcome of interest. Results Patients concurrently experienced post‐traumatic growth and stress following peritoneal dialysis. The initiation of patients’ education level, employment status and self‐perceived stress were all found to relate to growth among Chinese CAPD patients. There was not sufficient evidence to suggest that self‐perceived burden was related to experiencing growth.

IntroductionInflammation play important roles in the initiation and progression of acute lung injury (ALI), acute respiratory distress syndrome (ARDS), septic shock, clotting dysfunction, or even death associated with SARS-CoV-2 infection. However, the pathogenic mechanisms underlying SARS-CoV-2-induced hyperinflammation are still largely unknown.MethodsThe animal model of septic shock and ALI was established after LPS intraperitoneal injection or intratracheal instillation. Bone marrow-derived macrophages (BMDMs) from WT and BPOZ-2 KO mouse strains were harvested from the femurs and tibias of mice. Immunohistology staining, ELISA assay, coimmunoprecipitation, and immunoblot analysis were used to detect the histopathological changes of lung tissues and the expression of inflammatory factors and protein interaction.Results and conclusionsWe show a distinct mechanism by which the SARS-CoV-2 N (SARS-2-N) protein targets Bood POZ-containing gene type 2 (BPOZ-2), a scaffold protein for the E3 ubiquitin ligase Cullin 3 that we identified as a negative regulator of inflammatory responses, to promote NLRP3 inflammasome activation. We first demonstrated that BPOZ-2 knockout (BPOZ-2 KO) mice were more susceptible to lipopolysaccharide (LPS)-induced septic shock and ALI and showed increased serum IL-1β levels. In addition, BMDMs isolated from BPOZ-2 KO mice showed increased IL-1β production in response to NLRP3 stimuli. Mechanistically, BPOZ-2 interacted with NLRP3 and mediated its degradation by recruiting Cullin 3. In particular, the expression of BPOZ-2 was significantly reduced in lung tissues from mice infected with SARS-CoV-2 and in cells overexpressing SARS-2-N. Importantly, proinflammatory responses triggered by the SARS-2-N were significantly blocked by BPOZ-2 reintroduction. Thus, we concluded that BPOZ-2 is a negative regulator of the NLPR3 inflammasome that likely contributes to SARS-CoV-2-induced hyperinflammation.

The study takes 10 urban agglomerations in China as the research object, focusing on the Chengdu-Chongqing urban agglomeration, and applies Data Envelopment Analysis (DEA) to measure and compare their scientific input and output efficiency of universities. First, this paper analyzes the input and output of scientific research in universities in major provinces in China in detail. Second, according to the construction principles of the indicator system, using qualitative interview to construct evaluation indicators of university research efficiency. Third, using DEA method, first analyze the input and output profile of some urban agglomeration universities such as Chengdu-Chongqing economic circle, measure and compare their research input and output efficiency, then compare and analyze the research efficiency of research-type sample universities within Chengdu-Chongqing economic circle, and conduct a projection study of non-DEA effective sample universities. The main conclusions are as follows: first, the average efficiency of scientific research in universities in Chengdu-Chongqing and other urban agglomerations in 2020 has slightly increased compared with that in 2016, but the gap between urban agglomerations is prominent, and the innovation level of scientific research in higher education institutions in urban agglomerations needs to be improved. Second, there is a mismatch between the themes of research, funding and human resources in research-oriented universities in the Chengdu-Chongqing economic circle. Third, there is considerable room for improvement in research efficiency, and the influence of scale on overall efficiency is weak. We found that excessive investment in scientific research in universities is the main reason for the non-effect.

ObjectiveThis study aimed to determine the hospitalization rates, length of stay, age at the time of admission, and sex distribution for major psychiatric disorders in children and adolescents and provide a reference for early intervention for these diseases and distribution of medical resources in hospitals.MethodsWe screened 4,423 patients in the child and adolescent wards of the Anhui Provincial Mental Health Center from 2001 to 2020, and examined the top four (81.1%) mental health disorders that accounted for the overall proportion of patients admitted, namely schizophrenia (SCZ) (45.7%), depressive disorder (DD) (14.5%), bipolar disorder (BD) (9.3%), and childhood emotional disorder (CED) (11.6%), and for each disorder, the percentage of hospitalization, length of stay, age at admission, and sex distribution were analyzed.ResultsFrom 2001 to 2020, there was a significantly decreasing trend in the proportion of hospitalizations for SCZ (p < 0.001) and an increasing trend for depression and CED (p < 0.001). In terms of length of stay, SCZ was significantly longer than the other three disorders (p < 0.001), whereas there was no significant difference between DD, BD, and CED, and there was no significant trend in length of stay for any of the four disorders. The age at admission for CED was significantly lower than that for the other three disorders (p < 0.001). There was a decreasing trend in the age at admission for DD (p = 0.011) and an increasing trend for BD (p = 0.001). A significant increase in the number of female patients admitted for SCZ, DD, and CED was observed, while there was no significant change in the sex ratio for BD.ConclusionAlthough there is a significant downward trend in the percentage of hospitalizations for SCZ, it is still the most common psychiatric disorder in children and adolescents. We observed a significant increase in the percentage of hospitalizations for DD and CED. In addition, the proportion of female patients being hospitalized is on the rise, and this aspect requires continuous attention.

Dysregulation of lipid metabolism and transport contribute to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Here the authors identify GP73 as a TBC-domain Rab GTPase-activating protein that regulates very low-density lipoprotein export and promotes NAFLD development in mice.

Compounds that selectively modulate multiple targets can provide clinical benefits and are an alternative to traditional highly selective agents for unique targets. High-throughput screening (HTS) for multitarget-directed ligands (MTDLs) using approved drugs, and fragment-based drug design has become a regular strategy to achieve an ideal multitarget combination. However, the unexpected presence of pan-assay interference compounds (PAINS) suspects in the development of MTDLs frequently results in nonspecific interactions or other undesirable effects leading to artefacts or false-positive data of biological assays. Publicly available filters can help to identify PAINS suspects; however, these filters cannot comprehensively conclude whether these suspects are “bad” or innocent. Additionally, these in silico approaches may inappropriately label a ligand as PAINS. More than 80% of the initial hits can be identified as PAINS by the filters if appropriate biochemical tests are not used resulting in false positive data that are unacceptable for medicinal chemists in manuscript peer review and future studies. Therefore, extensive offline experiments should be used after online filtering to discriminate “bad” PAINS and avoid incorrect evaluation of good scaffolds. We suggest that the use of “Fair Trial Strategy” to identify interesting molecules in PAINS suspects to provide certain structure‒function insight in MTDL development.

Soil aggregates provide spatially heterogeneous microhabitats that support the coexistence of soil microbes. However, there remains a lack of detailed assessment of the mechanism underlying aggregate-microbiome formation and impact on soil function. Here, the microbial assemblages within four different aggregate sizes and their correlation with microbial activities related to nutrient cycling were studied in rice fields in Southern China. The results show that deterministic and stochastic processes govern bacterial and fungal assemblages in agricultural soil, respectively. The contribution of determinism to bacterial assemblage improved as aggregate size decreased. In contrast, the importance of stochasticity to fungal assemblage was higher in macroaggregates (>0.25 mm in diameter) than in microaggregates (

Accurate calculation of the electromagnetic force distribution of transformer windings under different loads and fault conditions is of great significance for transformer maintenance, condition evaluation and life prediction. Due to the influence of offshore wind power systems, offshore wind power transformers have high harmonic content and large changes in load rates, which can easily cause the coil destabilization, winding deformation or even damage because of the uneven distribution of the electromagnetic force. To improve the accuracy of electromagnetic force calculation, this paper proposes a fractional order numerical method. First, a three-dimensional axisymmetric transformer model and a symmetrical lumped parameter equivalent circuit model are established, respectively, based on field-circuit coupling. Second, the fractional order approximation of circuit components is realized by using the improved Oustaloup filter. In the fractional order model, the transformer is replaced by the lumped parameter equivalent circuit model. Third, as in the calculation process for integer order electromagnetic force, the integer order current has a large error, and the current waveform does not match the actual power frequency. The fractional order current and electromagnetic force at the 0.9 order are closer to the rated value. Finally, the effects of different load rates, three-phase short circuits and harmonic conditions are studied with the fractional order model. Compared with the traditional integer order finite element electromagnetic model, the fractional order equivalent circuit model established in this paper is more accurate and suitable for electromagnetic force calculation. The proposed method is significant for the structural design and state detection of transformers and also could be applied in the analysis of other dry-type transformers.

Abstract Lung cancer is the most malignant tumor in the worldwide. About 3%‐5% non‐small cell lung cancer (NSCLC) patients carry anaplastic lymphoma kinase (ALK) gene fusions and receive great benefits from ALK‐targeted therapy. However, drug resistance inevitably occurs even with the most potent inhibitor drug lorlatinib. About half of the resistance are caused by alteration in ALK proteins for earlier ALK TKI drugs and near one‐third of loratinib resistant cases are caused by compound mutations without current effective treatment strategy in clinic. Novel strategies are in great need to overcome drug resistance. Lately, two novel strategies have been developed and attracted great attentions for their potentials to overcome drug resistance problems: (1) developed small compact macrocyclic ALK kinase inhibitors and (2) developed ALK targeted proteolysis‐targeting chimera (PROTAC) drugs. The macrocyclic molecules are small and compact in size, brain barrier permeable, and highly potent against lorlatinib‐resistant compound mutations. Developed ALK targeted PROTAC molecules could degrade oncogenic ALK driver proteins. Some showed superiority in killing ALK positive cancer cells and inhibiting the growth of cells expressing G1202R resistant ALK proteins comparing to inhibitor drugs. The update on these two treatment strategies was reviewed.

The wood sorrel family, Oxalidaceae, is mainly composed of annual or perennial herbs, a few shrubs, and trees distributed from temperate to tropical zones. Members of Oxalidaceae are of high medicinal, ornamental, and economic value. Despite the rich diversity and value of Oxalidaceae, few molecular markers or plastomes are available for phylogenetic analysis of the family. Here, we reported four new whole plastomes of Oxalidaceae and compared them with plastomes of three species in the family, as well as the plastome of Rourea microphylla in the closely related family Connaraceae. The eight plastomes ranged in length from 150,673 bp (Biophytum sensitivum) to 156,609 bp (R. microphylla). Genome annotations revealed a total of 129–131 genes, including 83–84 protein-coding genes, eight rRNA genes, 37 tRNA genes, and two to three pseudogenes. Comparative analyses showed that the plastomes of these species have minor variations at the gene level. The smaller plastomes of herbs B. sensitivum and three Oxalis species are associated with variations in IR region sizes, intergenic region variation, and gene or intron loss. We identified sequences with high variation that may serve as molecular markers in taxonomic studies of Oxalidaceae. The phylogenetic trees of selected superrosid representatives based on 76 protein-coding genes corroborated the Oxalidaceae position in Oxalidales and supported it as a sister to Connaraceae. Our research also supported the monophyly of the COM (Celastrales, Oxalidales, and Malpighiales) clade.