Search

Cloud contamination is a common problem in Earth observation that hinders various remote sensing applications. To address this problem, recent studies have employed deep neural networks and multi-modal data fusion to reconstruct cloud-free optical imagery. However, this task faces many challenges, such as: (1) the scarcity of suitable multi-modal datasets; (2) the ineffective use of feature correlations; and (3) the limited applicability of existing models. To overcome these challenges, this study proposes a novel solution that fuses high-spatial SAR and low-spatial optical data to reconstruct high-quality cloud-free multi-spectral optical products. First, a curated benchmark dataset, named SMILE-CR, is created with a realistic cloud simulation strategy. The SMILE-CR serves as a global and multi-modal cloud removal dataset for the Landsat-8 sensor, with Sentinel-1 and MODIS data as additional supplementary data. Second, a Transformer-based cloud removal network, abbreviated as CRformer, is developed with two novel modules: multi-head dense and sparse attention and multi-scale gated-dconv feed-forward network. The CRformer achieves global attention while suppressing the weak correlations and enhancing the multi-scale cloud features by filtering out invalid features. The performance of the proposed method is evaluated through extensive experiments. The results show that the CRformer surpasses the state-of-the-art cloud removal methods with significant improvements in both quantitative and qualitative metrics. The fusion of MODIS and Sentinel-1 data is shown to be effective and necessary in reconstructing Landsat-8 observations. Moreover, the CRformer model can be readily applied to reconstruct time-series cloud-free Landsat-8 products in Wuhan city, which can improve the average accuracy of land cover mapping by over 3%.

Iron overload occurs due to excessive iron intake compared to the body’s demand, leading to iron deposition and impairment of multiple organ functions. Our previous study demonstrated that chronic oral administration of ferric citrate (FC) caused colonic inflammatory injury. However, the precise mechanism underlying this inflammatory response remains unclear. The current study aims to investigate the mechanism by which iron overload induced by FC exposure leads to colonic inflammation. To accomplish this, mice were orally exposed to three different concentrations of FC (71 mg/kg/bw (L), 143 mg/kg/bw (M) and 286 mg/kg/bw (H)) for continuous 16 weeks, with the control group receiving ultrapure water (C). Exposure to FC caused disturbances in the excretory system, altered colonic flora alpha diversity, and enriched pathogenic bacteria, such as Mucispirillum, Helicobacter, Desulfovibrio, and Shigella. These changes led to structural disorders of the colonic flora and an inflammatory response phenotype characterized by inflammatory cells infiltration, atrophy of intestinal glands, and irregular thickening of the intestinal wall. Mechanistic studies revealed that FC-exposure activated the NF-κB signaling pathway by up-regulating TLR4, MyD88, and NF-κB mRNA levels and protein expression. This activation resulted in increased production of pro-inflammatory cytokines, further contributing to the colonic inflammation. Additionally, in vitro experiments in SW480 cells confirmed the activation of NF-κB signaling pathway by FC exposure, consistent with the in vivo findings. The significance of this study lies in its elucidation of the mechanism by which iron overload caused by FC exposure leads to colonic inflammation. By identifying the role of pathogenic bacteria and the NF-κB signaling pathway, this study could potentially offer a crucial theoretical foundation for the research on iron overload, as well as provide valuable insights for clinical iron supplementation.

Gut microbes especially the beneficial ones play an important role in maintaining human health. At present, the research methods for intestinal microbes are mainly based on non-culture technologies such as metagenomics. The relationship between intestinal microbes and the body’s health can be found by using metagenomic sequencing technology. Researchers have found that most of the bacteria in the gut are uncultured, and their molecular mechanisms of action are unclear. Culturomics can be used to successfully isolate and culture some intestinal bacteria difficult to culture by improving the composition of culture medium and optimizing the culture conditions. The application of culturomics provides technical support for research on the functions of intestinal bacteria in the host and further screening of beneficial intestinal bacteria. Therefore, using culturomics technology to cultivate more beneficial intestinal bacteria and studying their phenotypes and gene functions are future research priorities. This article reviews the culturomics of and the cultivation methods for intestinal beneficial bacteria for the purpose of providing a reference for the cultivation of beneficial intestinal microorganisms for human health.

Objective: We aimed to evaluate the safety and efficacy of delaying lung transplantation until morning for donors with cross-clamp times occurring after 1:30 am. Methods: All consented adult lung transplant recipients between March 2018 and May 2022 with donor cross-clamp times between 1:30 am and 5 am were enrolled prospectively in this study. Skin incision for enrolled recipients was delayed until 6:30 am (Night group). The control group was identified using a 1:2 logistic propensity score method and included recipients of donors with cross-clamp times occurring at any other time of day (Day group). Short- and medium-term outcomes were examined between groups. The primary endpoint was early mortality (30-day and in-hospital). Results: Thirty-four patients were enrolled in the Night group, along with 68 well-matched patients in the Day group. As expected, donors in the Night group had longer cold ischemia times compared to the Day group (344 minutes vs 285 minutes; P

Abstract Background Cytoplasmic male sterility (CMS) plays a crucial role in hybrid production. K-type CMS, a cytoplasmic male sterile line of wheat with the cytoplasms of Aegilops kotschyi, is widely used due to its excellent characteristics of agronomic performance, easy maintenance and easy restoration. However, the mechanism of its pollen abortion is not yet clear. Results In this study, wheat K-type CMS MS(KOTS)-90-110 (MS line) and it’s fertile near-isogenic line MR (KOTS)-90-110 (MR line) were investigated. Cytological analysis indicated that the anthers of MS line microspore nucleus failed to divide normally into two sperm nucleus and lacked starch in mature pollen grains, and the key abortive period was the uninucleate stage to dinuclear stage. Then, we compared the transcriptome of MS line and MR line anthers at these two stages. 11,360 and 5182 differentially expressed genes (DEGs) were identified between the MS and MR lines in the early uninucleate and binucleate stages, respectively. Based on GO enrichment and KEGG pathways analysis, it was evident that significant transcriptomic differences were “plant hormone signal transduction”, “MAPK signaling pathway” and “spliceosome”. We identified 17 and 10 DEGs associated with the IAA and ABA signal transduction pathways, respectively. DEGs related to IAA signal transduction pathway were downregulated in the early uninucleate stage of MS line. The expression level of DEGs related to ABA pathway was significantly upregulated in MS line at the binucleate stage compared to MR line. The determination of plant hormone content and qRT-PCR further confirmed that hormone imbalance in MS lines. Meanwhile, 1 and 2 DEGs involved in ABA and Ethylene metabolism were also identified in the MAPK cascade pathway, respectively; the significant up regulation of spliceosome related genes in MS line may be another important factor leading to pollen abortion. Conclusions We proposed a transcriptome-mediated pollen abortion network for K-type CMS in wheat. The main idea is hormone imbalance may be the primary factor, MAPK cascade pathway and alternative splicing (AS) may also play important regulatory roles in this process. These findings provided intriguing insights for the molecular mechanism of microspore abortion in K-type CMS, and also give useful clues to identify the crucial genes of CMS in wheat.

Insect male genitalia show an evolutionarily variable morphology that is valuable for both species identification and phylogenetic analyses. However, we often encounter some difficulties when conducting relevant studies due to only quantitative variations exhibited in male genitalia. In this study, based on the taxonomy of the Macrolycus dotatus species group (a total of seven species, including three new species described here), we analyzed the male genitalia shapes by GM and then constructed the phenotypic relationships by UPGMA, NJ and MP analyses. The results demonstrated that the species could be well delineated by the shape of male genitalia, and the produced phenograms frequently recovered phenotypic similarity between the coupled species, including M. atronotatimimus sp. nov. + M. huoditangensis sp. nov. and M. aemulus + M. dotatus, which is useful for making comparisons in species descriptions. Meanwhile, the MP analysis of male genitalia shape using two landmark configurations is considered reliable in inferring the phylogenetic relationship among species in terms of the consistency between its topologies and the molecular phylogeny. This study sheds new light on improving the morphological taxonomy of insects in lower grades while fully utilizing the taxonomic value of male genitalia in a phylogenetic context.

Abstract Chongqing was seriously affected by hand, foot, and mouth disease (HFMD), but the relationships between daily mean temperature and the incidence of HFMD remain unclear. This study used distributed lag nonlinear model to evaluate the effect of daily mean temperature on the incidence of HFMD in children aged

Abstract Core genome multilocus sequence typing (cgMLST) is commonly used to classify bacterial strains into different types, for taxonomical and epidemiological applications. However, cgMLST schemes require central databases for the nomenclature of new alleles and sequence types, which must be synchronized worldwide and involve increasingly intensive calculation and storage demands. Here, we describe a distributed cgMLST (dcgMLST) scheme that does not require a central database of allelic sequences and apply it to study evolutionary patterns of epidemic and endemic strains of the genus Neisseria. We classify 69,994 worldwide Neisseria strains into multi-level clusters that assign species, lineages, and local disease outbreaks. We divide Neisseria meningitidis into 168 endemic lineages and three epidemic lineages responsible for at least 9 epidemics in the past century. According to our analyses, the epidemic and endemic lineages experienced very different population dynamics in the past 100 years. Epidemic lineages repetitively emerged from endemic lineages, disseminated worldwide, and apparently disappeared rapidly afterward. We propose a stepwise model for the evolutionary trajectory of epidemic lineages in Neisseria, and expect that the development of similar dcgMLST schemes will facilitate epidemiological studies of other bacterial pathogens.

Abstract As a highly enriched endosomal protein within neuronal cells, NSG1 has been discovered to facilitate the process of epithelial-mesenchymal transition (EMT) in esophageal squamous cell carcinoma (ESCC). However, the precise mechanisms behind this phenomenon have yet to be elucidated. The pivotal role of transforming growth factor-β (TGF-β) in triggering the EMT and its significant contribution towards tumor metabolic reprogramming—responsible for EMT activation—has been robustly established. Nevertheless, the extent of TGF-β involvement in the NSG1-mediated EMT within ESCC and the processes through which metabolic reprogramming participates remain ambiguous. We accessed an array of extensive public genome databases to analyze NSG1 expression in ESCC. Regulation of TGF-β by NSG1 was analyzed by transcriptome sequencing, quantitative Real-Time PCR (qRT-PCR), co-immunoprecipitation (CO-IP), and immunofluorescence (IF). Additionally, cellular functional assays and western blot analyses were conducted to elucidate the effect of NSG1 on TGF-β/Smad signaling pathway, as well as its role in ESCC cell metastasis and proliferation. We validated the influence of the NSG1/TGF-β axis on metabolic reprogramming in ESCC by measuring extracellular acidification, glucose uptake, and lactate production. Our findings identify an oncogenic role for NSG1 in ESCC and show a correlation between high NSG1 expression and poor prognosis in ESCC patients. Additional research indicated TGF-β’s involvement in the NSG1-induced EMT process. From a mechanistic perspective, NSG1 upregulates TGF-β, activating the TGF-β/Smad signaling pathway and subsequently fostering the EMT process by inducing cell metabolic reprogramming—evident from elevated glycolysis levels. In conclusion, our study highlights the NSG1/TGF-β axis as a promising therapeutic target for ESCC.

Researchers are increasingly interested in discovering new pancreatic lipase inhibitors as anti-obesity ingredients. Medicine-and-food homology plants contain a diverse set of natural bioactive compounds with promising development potential. This study screened and identified potent pancreatic lipase inhibitors from 20 commonly consumed medicine-and-food homology plants using affinity ultrafiltration combined with spectroscopy and docking simulations. The results showed that turmeric exhibited the highest pancreatic lipase-inhibitory activity, and curcumin, demethoxycurcumin, and bisdemethoxycurcumin were discovered to be potent pancreatic lipase inhibitors within the turmeric extract, with IC50 values of 0.52 ± 0.04, 1.12 ± 0.05, and 3.30 ± 0.08 mg/mL, respectively. In addition, the enzymatic kinetics analyses demonstrated that the inhibition type of the three curcuminoids was the reversible competitive model, and curcumin exhibited a higher binding affinity and greater impact on the secondary structure of pancreatic lipase than found with demethoxycurcumin or bisdemethoxycurcumin, as observed through fluorescence spectroscopy and circular dichroism. Furthermore, docking simulations supported the above experimental findings, and revealed that the three curcuminoids might interact with amino acid residues in the binding pocket of pancreatic lipase through non-covalent actions, such as hydrogen bonding and π-π stacking, thereby inhibiting the pancreatic lipase. Collectively, these findings suggest that the bioactive compounds of turmeric, in particular curcumin, can be promising dietary pancreatic lipase inhibitors for the prevention and management of obesity.

Freeform off-axis reflective systems are significantly more difficult to align and assemble owing to their asymmetric surface shapes and system structures. In this study, a freeform surface system design method with low coupling position error sensitivity (FCPESM) was proposed. First, we established a mathematical model of a reflective system when it was perturbed by coupling position errors and used the clustering-microelement method to establish the coupling error sensitivity evaluation function. The evaluation function was then applied to the design process of a freeform surface off-axis three-mirror optical system. The results showed that the FCPESM optical design method can significantly relax the assembly tolerance requirements of optical systems on the basis of ensuring image performance. In this study, the reflective system was perturbed by tilt and decenter simultaneously, and the disturbance mechanism of position errors on optical systems was further improved. Through this research, freeform surface systems with both image performance and error sensitivity can be obtained, which makes freeform off-axis reflective systems with better engineering realizability.

Background Effective discrimination of lung adenocarcinoma (LUAD) in situ (AIS) from benign pulmonary nodules (BPN) is critical for the early diagnosis of AIS. Our pilot study in a small cohort of 90 serum samples has shown that serum interleukin 6 (IL-6) detection can distinguish AIS from BPN and health controls (HC). In this study, we intend to comprehensively define the diagnostic value of individual and combined detection of serum IL-6 related to the traditional tumor markers carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1) for AIS. Methods The diagnostic performance of serum IL-6 along with CEA and CYFRA21-1 were evaluated in a large cohort of 300 serum samples by a chemiluminescence immunoassay and an electrochemiluminescence immunoassay. A training set comprised of 65 AIS, 65 BPN, and 65 HC samples was used to develop the predictive model for AIS. Data obtained from an independent validation set was applied to evaluate and validate the predictive model. Results In the training set, the levels of serum IL-6 and CEA in the AIS group were significantly higher than those in the BPN/HC group (P < 0.05). There was no significant difference in serum CYFRA21-1 levels between the AIS group and the BPN/HC group (P> 0.05). Serum IL-6 and CEA levels for AIS patients showed an area under the curve (AUC) of 0.622 with 23.1% sensitivity at 90.7% specificity, and an AUC of 0.672 with 24.6% sensitivity at 97.6% specificity, respectively. The combination of serum IL-6 and CEA presented an AUC of 0.739, with 60.0% sensitivity at 95.4% specificity. The combination of serum IL-6 and CEA showed an AUC of 0.767 for AIS patients, with 57.1% sensitivity at 91.4% specificity in the validation set. Conclusions IL-6 shows potential as a prospective serum biomarker for the diagnosis of AIS, and the combination of serum IL-6 with CEA may contribute to increased accuracy in AIS diagnosis. However, it is worth noting that further research is still necessary to validate and optimize the diagnostic efficacy of these biomarkers and to address potential sensitivity limitations.

Background: Mpox re-emerged worldwide with the multi-country outbreaks that occurred in May 2022, threatening the public health of human beings. Methods: This rapid systematic review summarized mpox reinfection cases documented. Electronic databases (PubMed, MedRxiv, and Social Science Research Network) were searched without time limitation, using the keywords “mpox,” “monkeypox,” & “reinfection,” “reoccur,” “reoccurrence,” “episode,” and “relapse”. All laboratory-confirmed cases of mpox reinfection published in the literature were included in this study. Results: A total of seven publications (nine cases) from Africa, Europe, and South America were included. All mpox reinfection cases were male, with a median age of 36; 88.89% of cases had unprotected sexual behaviors with other males before each illness episode. The average onset interval between the two episodes was about 4 months. Perianal lesions and lymphadenopathy were major symptoms in both episodes, and no differences in clinical severity were reported between the two episodes. The mean duration of the two episodes was approximately 22 days and 13 days, respectively; which the mean duration of the second episode was shorter than the first infection (t = 2.17, p = 0.0487). Sexually transmitted infections were commonly concurrent among most cases, accounting for 55.6% and 77.8% in the two episodes, respectively. Full vaccination against mpox was rare among reinfection cases. Conclusion: A second infection is possible even in a short period. Reinforcing monitoring, reducing high-risk behaviors, and heightening health education regarding mpox for high-risk populations are crucial to limit mpox spread, including persons with a history of mpox infection.

Globally, millions of individuals are impacted by neurodegenerative disorders including Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Alzheimer's disease (AD). Although a great deal of energy and financial resources have been invested in disease-related research, breakthroughs in therapeutic approaches remain elusive. The breakdown of cells usually happens together with the onset of neurodegenerative diseases. However, the mechanism that triggers neuronal loss is unknown. Lipid peroxidation, which is iron-dependent, causes a specific type of cell death called ferroptosis, and there is evidence its involvement in the pathogenic cascade of neurodegenerative diseases. However, the specific mechanisms are still not well known. The present article highlights the basic processes that underlie ferroptosis and the corresponding signaling networks. Furthermore, it provides an overview and discussion of current research on the role of ferroptosis across a variety of neurodegenerative conditions.

Background. Lung transplant surgery creates surgical pulmonary vein isolation (PVI) as a routine part of the procedure. However, many patients with pretransplant atrial fibrillation continue to have atrial fibrillation at 1 y. We hypothesized that the addition of electrical PVI and left atrial appendage isolation/ligation (LAL) to the lung transplant procedure restores sinus rhythm at 1 y in patients with pretransplant atrial fibrillation. Methods. We retrospectively reviewed all adult lung transplant recipients at the University of California Los Angeles from April 2006 to August 2021. All patients with pretransplant atrial fibrillation underwent concomitant PVI/LAL and were compared with lung transplant recipients without preoperative atrial fibrillation. In-hospital outcomes; 1-y survival; and the incidence of stroke, cardiac readmissions, repeat ablations, and sinus rhythm (composite endpoint) were examined at 1 y for the PVI/LAL cohort. Results. Sixty-one lung transplant recipients with pretransplant atrial fibrillation underwent concomitant PVI/LAL. No patient in the PVI/LAL cohort required cardiac-related readmission or catheter ablation for atrial fibrillation within 1 y of transplantation. Freedom from the composite endpoint of death, stroke, cardiac readmission, and repeat ablation for atrial fibrillation at 1 y was 85% (95% confidence interval, 73%-92%) for lung transplant recipients treated with PVI/LAL. Conclusions. The addition of PVI/LAI to the lung transplant operation in patients with pretransplant atrial fibrillation was safe and effective in maintaining sinus rhythm and baseline risk of stroke at 1 y.

To promote the potentially industrial applications of thinned unripe kiwifruits, two deep eutectic solvent-based methods, including deep eutectic solvent-assisted extraction (DAE) and microwave-assisted deep eutectic solvent extraction (MDE), were optimized for the extraction of polysaccharides from thinned unripe kiwifruits (YKP). Results showed that the yields of YKP-D prepared by DAE and YKP-DM prepared by MDE were extremely higher than YKP-H prepared by hot water extraction. Furthermore, YKP-H, YKP-D, and YKP-DM were mainly composed of pectic polysaccharides, including homogalacturonan (HG) and rhamnogalacturonan I (RG I) domains. Besides, both YKP-D and YKP-DM exhibited stronger antioxidant, anti-glycosylation, and immunomodulatory effects than those of YKP-H, and their higher contents of uronic acids and bound polyphenols as well as lower molecular weights could partially contribute to their bioactivities. Overall, these results revealed that the developed MDE method could be utilized as a promising method for highly efficient extraction of YKP with superior beneficial effects.

BackgroundThe 2021 World Health Organization Classification of Central Nervous System Tumors updates glioma subtyping and grading system, and incorporates EGFR amplification (Amp) as one of diagnostic markers for glioblastoma (GBM).PurposeThis study aimed to describe the frequency, clinical value and molecular correlation of EGFR Amp in diffuse gliomas based on the latest classification.MethodsWe reviewed glioma patients between 2011 and 2022 at our hospital, and included 187 adult glioma patients with available tumor tissue for detection of EGFR Amp and other 59 molecular markers of interest. Clinical, radiological and pathological data was analyzed based on the status of EGFR Amp in different glioma subtypes.Results163 gliomas were classified as adult-type diffuse gliomas, and the number of astrocytoma, oligodendroglioma and GBM was 41, 46, and 76. EGFR Amp was more common in IDH-wildtype diffuse gliomas (66.0%) and GBM (85.5%) than IDH-mutant diffuse gliomas (32.2%) and its subtypes (astrocytoma, 29.3%; oligodendroglioma, 34.8%). EGFR Amp did not stratify overall survival (OS) in IDH-mutant diffuse gliomas and astrocytoma, while was significantly associated with poorer OS in IDH-wildtype diffuse gliomas, histologic grade 2 and 3 IDH-wildtype diffuse astrocytic gliomas and GBM.ConclusionOur study validated EGFR Amp as a diagnostic marker for GBM and still a useful predictor for shortened OS in this group.

ASPP2 and iASPP bind to p53 through their conserved ANK-SH3 domains to respectively promote and inhibit p53-dependent cell apoptosis. While crystallography has indicated that these two proteins employ distinct surfaces of their ANK-SH3 domains to bind to p53, solution NMR data has suggested similar surfaces. In this study, we employed multi-scale molecular dynamics (MD) simulations combined with free energy calculations to reconcile the discrepancy in the binding modes. We demonstrated that the binding mode based solely on a single crystal structure does not enable iASPP's RT loop to engage with p53's C-terminal linker-a verified interaction. Instead, an ensemble of simulated iASPP-p53 complexes facilitates this interaction. We showed that the ensemble-average inter-protein contacting residues and NMR-detected interfacial residues qualitatively overlap on ASPP proteins, and the ensemble-average binding free energies better match experimental KD values compared to single crystallgarphy-determined binding mode. For iASPP, the sampled ensemble complexes can be grouped into two classes, resembling the binding modes determined by crystallography and solution NMR. We thus propose that crystal packing shifts the equilibrium of binding modes towards the crystallography-determined one. Lastly, we showed that the ensemble binding complexes are sensitive to p53's intrinsically disordered regions (IDRs), attesting to experimental observations that these IDRs contribute to biological functions. Our results provide a dynamic and ensemble perspective for scrutinizing these important cancer-related protein-protein interactions (PPIs).

Although bone destruction and hypercalcemia without acute peripheral blast BCR-ABL-positive acute lymphoblastic leukemia (ALL) have been reported in children, they are rare in adults. Herein, we describe a case of BCR-ABL positive ALL with a triploid karyotype, WT1, and CDKN2A mutations with hypercalcemia and bone destruction as the first manifestations. Complete remission (CR) was achieved by induction chemotherapy. BCR-ABL turned negative after treatment with dasatinib. However, computed tomography and whole-body bone scan showed extensive bone destruction. Additionally, bone biopsy showed leukemic infiltration. After treatment with dasatinib and VMCP, leukemia recurred with positive BCR-ABL. The T315I mutation occurred. The patient was surgically diagnosed with calculous cholecystitis and achieved CR2 by postoperative orebatinib and VP regimens. Later, the patient died due to a severe pulmonary infection. BCR-ABL-positive ALL with bone destruction is rare and difficult to control using tyrosine kinase inhibitor chemotherapy alone. Therefore, further exploration of more effective treatments is needed.

Background: Although previous studies found that inflammatory bowel disease (IBD) and diverticular disease (DD) usually co-exist clinically, studies examining the relationship are spare.Aim: Our study aspires to investigate the causal correlation between the IBD [including ulcerative colitis (UC) and Crohn’s disease (CD)] and DD using the Mendelian randomization (MR) analysis.Methods: We conducted a two-sample bidirectional MR analysis using publicly available genome-wide association studies (GWAS) summary data. The single nucleotide polymorphism (SNP) data associated with DD and IBD were obtained from the Finnish Biobank and UK Biobank, respectively. Through secondary data analysis of all GWAS summary data, we systematically screened genetic instrumental variables. To address the impact of horizontal pleiotropy, several methods were employed, including the inverse variance-weighted method (IVW), maximum likelihood method, Egger regression method, weighted median method, and simple median method. These approaches aimed to detect and correct for the potential bias caused by horizontal pleiotropy.Results: Genetically predicted DD did not have a causal effect on IBD (OR 1.06, 95% CI 0.98–1.17, p = 0.15), and had no causal effect on UC (OR 1.10, 95% CI 0.94–1.20, p = 0.36) and CD (OR 1.03, 95% CI 0.92–1.16, p = 0.62) either. Furthermore, in the reverse MR analysis, we did not observe any significant causal effect of IBD on DD. Results of complementary methods showed consistent results with those of the IVW method.Conclusion: This study’s findings do not provide evidence for a causal relationship between IBD and DD, which contradicts the majority of observational studies.

Water droplets containing the SARS-CoV-2 virus, responsible for coronavirus 2019 transmission, were introduced into a controlled-temperature and -humidity chamber. The SARS-CoV-2 virus with green fluorescent protein tag in droplets was used to infect Caco-2 cells, with viability assessed through flow cytometry and microscopic counting. Whereas temperature fluctuations within typical indoor ranges (20°C–30°C) had minimal impact, we observed a notable decrease in infection rate as the surrounding air’s relative humidity increased. By investigating humidity levels between 20% and 70%, we identified a threshold of ≥40% relative humidity as most effective in diminishing SARS-CoV-2 infectivity. We also found that damage of the viral proteins under high relative humidity may be responsible for the decrease in their activity. This outcome supports previous research demonstrating a rise in the concentration of reactive oxygen species within water droplets with elevated relative humidity.

Depression is an incapacitating psychiatric disorder with increased risk through adolescence. Among other factors, children with family history of depression have significantly higher risk of developing depression. Early identification of pre-adolescent children who are at risk of depression is crucial for early intervention and prevention. In this study, we used a large longitudinal sample from the Adolescent Brain Cognitive Development (ABCD) Study (2658 participants after imaging quality control, between 9–10 years at baseline), we applied advanced machine learning methods to predict depression risk at the two-year follow-up from the baseline assessment, using a set of comprehensive multimodal neuroimaging features derived from structural MRI, diffusion tensor imaging, and task and rest functional MRI. Prediction performance underwent a rigorous cross-validation method of leave-one-site-out. Our results demonstrate that all brain features had prediction scores significantly better than expected by chance, with brain features from rest-fMRI showing the best classification performance in the high-risk group of participants with parental history of depression (N = 625). Specifically, rest-fMRI features, which came from functional connectomes, showed significantly better classification performance than other brain features. This finding highlights the key role of the interacting elements of the connectome in capturing more individual variability in psychopathology compared to measures of single brain regions. Our study contributes to the effort of identifying biological risks of depression in early adolescence in population-based samples.

Abstract Quantiles of precipitation are widely used in ensemble forecast systems. At present, the common practice is to provide precipitation amounts corresponding to different quantiles to users directly, which will make it difficult for users to extract reliable forecast information. Therefore, this study investigates the statistically optimal (using threat score (TS) as a metric) quantiles of precipitation in an ensemble forecast system constructed using the WRF V4.0 model. The main conclusions are as follows: The threat‐score‐optimal quantiles for light rain, moderate rain, heavy rain, rainstorm, and heavy rainstorm forecasts are 40%–60%, 60%–70%, 60%–80%, 70%–80%, and 80%, respectively. Overall, the optimal quantile increases with the rise in precipitation magnitude or the extension of forecast lead time. All the optimal quantile forecast products have higher TS than the corresponding control forecast, ensemble mean forecast, and probability‐matched ensemble mean forecast products. The merged threat‐score‐optimal quantile forecast product formed by combining the optimal quantile forecasts of different precipitation magnitudes shows obvious advantages over other products in statistical verification and case studies, and it shows good potential to be operationally implemented in the future.

Agriculture is the primary source of human survival, which provides the most basic living and survival conditions for human beings. As living standards continue to improve, people are also paying more attention to the quality and safety of agricultural products. Therefore, the detection of agricultural product quality is very necessary. In the past decades, the spectroscopy technique has been widely used because of its excellent results in agricultural quality detection. However, traditional spectral inspection methods cannot accurately describe the internal information of agricultural products. With the continuous research and development of optical properties, it has been found that the internal quality of an object can be better reflected by separating the properties of light, such as its absorption and scattering properties. In recent years, spatially resolved spectroscopy has been increasingly used in the field of agricultural product inspection due to its simple compositional structure, low-value cost, ease of operation, efficient detection speed, and outstanding ability to obtain information about agricultural products at different depths. It can also separate optical properties based on the transmission equation of optics, which allows for more accurate detection of the internal quality of agricultural products. This review focuses on the principles of spatially resolved spectroscopy, detection equipment, analytical methods, and specific applications in agricultural quality detection. Additionally, the optical properties methods and direct analysis methods of spatially resolved spectroscopy analysis methods are also reported in this paper.

3,3′,4′,4′,5-Polychlorinated biphenyls (PCB126) is classified as a persistent organic environmental pollutant that can cause liver damage by producing excessive reactive oxygen species (ROS). ROS also can stimulate neutrophil extracellular traps (NETs) formation, which cause damage to organism if NETs are produced in excess. Melatonin is generally considered to possess strong antioxidant and anti-inflammation prosperities, but it is unclear whether it can alleviate PCB126-induced injury. To explore whether PCB126-induced liver injury is related to the formation of NETs and whether melatonin has a potent protective effect, we established PCB126 exposure/ PCB126 and melatonin co-treatment mouse models by gavage. To further clarify the specific mechanism, we also cultured neutrophils and AML12 cells to replicate in vivo model. Here, we found PCB126 exposure resulted in an elevation in the activities of MDA, LPO, PCO, and 8-OHdG, and a reduction in the activities of CAT, GSH-PX and SOD. We found that PCB126 exposure led to an elevation in the expression levels of chemokines (CCL2, CCL3, CCL4, CXCL12, and CXCL8) and marker factors for NETs formation (MPO, NE, NOX2, PKCα, and PKCζ) in the PCB126 group. IF, SYTOX staining, and SEM results also revealed that PCB126 could stimulate NETs formation. In addition, results of a co-culture system of PBNs and AML12 cells revealed that the expression levels of inflammatory cytokines (IL-1β, IL-6, and TNF-α) significantly decreased and the expression levels of metabolism factors (Fas, Acc, and Srebp) slightly decreased for scavenging NETs, indicating NETs formation aggravated PCB126-induced hepatic damages. Noteworthy, treatment with melatonin reversed these results. In summary, our findings revealed that melatonin alleviated hepatic damage aggravated by PCB126-induced ROS-dependent NETs formation through suppressing excessive ROS production. This finding not only enriches toxicological mechanism of PCB126, but more importantly extends biological effects of melatonin and its potential application values.

Ion conductive membranes (ICMs) with highly conductive proton selectivity are of significant importance and greatly desired for energy storage devices. However, it is extremely challenging to construct fast proton-selective transport channels in ICMs. Herein, a membrane with highly conductive proton selectivity was fabricated by incorporating porous carbon sieving nanospheres with a hollow structure (HCSNs) in a polymer matrix. Due to the precise ion sieving ability of the microporous carbon shells and the fast proton transport through their accessible internal cavities, this advanced membrane presented a proton conductivity (0.084 S·cm−1) superior to those of a commercial Nafion 212 (N212) membrane (0.033 S·cm−1) and a pure polymer membrane (0.049 S·cm−1). The corresponding proton selectivity of the membrane (6.68 × 105 S·min·cm−3) was found to be enhanced by about 5.9-fold and 4.3-fold, respectively, compared with those of the N212 membrane (1.13 × 105 S·min·cm−3) and the pure membrane (1.56 × 105 S·min·cm−3). Low-field nuclear magnetic resonance (LF-NMR) clearly revealed the fast proton-selective transport channels enabled by the HCSNs in the polymeric membrane. The proposed membrane exhibited an outstanding energy efficiency (EE) of 84% and long-term stability over 1400 cycles with a 0.065% capacity decay per cycle at 120 mA·cm−2 in a typical vanadium flow battery (VFB) system.

Abstract Background The latest fifth edition of the World Health Organization (WHO) classification of the central nervous system (CNS) tumors (WHO CNS 5 classification) released in 2021 defined astrocytoma, IDH‐mutant, Grade 4. However, the understanding of this subtype is still limited. We conducted this study to describe the features of astrocytoma, IDH‐mutant, Grade 4 and explored the similarities and differences between histological and molecular subtypes. Methods Patients who underwent surgery from January 2011 to January 2022, classified as astrocytoma, IDH‐mutant, Grade 4 were included in this study. Clinical, radiological, histopathological, molecular pathological, and survival data were collected for analysis. Results Altogether 33 patients with astrocytoma, IDH‐mutant, Grade 4 were selected, including 20 with histological and 13 with molecular WHO Grade 4 astrocytoma. Tumor enhancement, intratumoral‐necrosis like presentation, larger peritumoral edema, and more explicit tumor margins were frequently observed in histological WHO Grade 4 astrocytoma. Additionally, molecular WHO Grade 4 astrocytoma showed a tendency for relatively longer overall survival, while a statistical significance was not reached (47 vs. 25 months, p = 0.22). TP53, CDK6, and PIK3CA alteration was commonly observed, while PIK3R1 (p = 0.033), Notch1 (p = 0.027), and Mycn (p = 0.027) alterations may affect the overall survival of molecular WHO Grade 4 astrocytomas. Conclusions Our study scrutinized IDH‐mutant, Grade 4 astrocytoma. Therefore, further classification should be considered as the prognosis varied between histological and molecular WHO Grade 4 astrocytomas. Notably, therapies aiming at PIK3R1, Notch 1, and Mycn may be beneficial.

Abstract Osteoporosis is not well treated due to the difficulty of finding commonalities between the various types of it. Iron homeostasis is a vital component in supporting biochemical functions, and iron overload is recognized as a common risk factor for osteoporosis. In this research, we found that there is indeed evidence of iron accumulation in the bone tissue of patients with osteoporosis and REPIN1, as an origin specific DNA binding protein, may play a key role in this process. We revealed that sh-Repin1 therapy can rescue bone loss in an iron-overload-induced osteoporosis mouse model. Knockdown of Repin1 can inhibit apoptosis and enhance the resistance of osteoblasts to iron overload toxicity. REPIN1 promoted apoptosis by regulating iron metabolism in osteoblasts. Mechanistically, knockdown of Repin1 decreased the expression of Lcn2, which ameliorated the toxic effects of intracellular iron overload. The anti-iron effect of lentivirus sh-Repin1 was partially reversed or replicated by changing LCN2 expression level via si-RNA or plasmid, which indirectly verified the key regulatory role of LCN2 as a downstream target. Furthermore, the levels of BCL2 and BAX, which play a key role in the mitochondrial apoptosis pathway, were affected. In summary, based on the results of clinical specimens, animal models and in vitro experiments, for the first time, we proved the key role of REPIN1 in iron metabolism-related osteoporosis.

Porous structures and surface morphology of bone tissue scaffolds play an important role in improving the biocompatibility and antibacterial properties for bone repair. In this study, we investigated the effect of different anodic oxidation parameters on the nanotubes morphology in 3D printed porous titanium scaffolds. Micron-scale pores were fabricated by 3D printing first, and then the nano-scale tubes were obtained via anodizing treatments. The results demonstrated that the morphology of the nanotubes depended on the anodic oxidation time and voltage, respectively. Longer anodic oxidation led to the formation of circle-like nanotubes, and the diameter of the nanotubes increased with the voltage. The scaffolds anodized at 30 V showed the best cell proliferation potential. The presence of nanotubes on the surface of scaffold altered the adhesion of bacteria so that it improved the antibacterial properties of scaffold. The formation of nanotubes improved the drug-loading ability of the scaffold, which are used for loading of minocycline antibacterial drugs. The proposed 3D printed porous Ti6Al4V scaffold with nanotubes surface modification showed obvious antibacterial effect, which is expected to have a promising application in antibacterial bone prosthesis.

Abstract Activation of endogenous neural stem cells (NSCs) is greatly significant for the adult neurogenesis; however, it is extremely limited in the spinal cord after injury. Recent evidence suggests that accumulation of protein aggregates impairs the ability of quiescent NSCs to activate. Ubiquitin c-terminal hydrolase l-1 (UCHL1), an important deubiquitinating enzyme, plays critical roles in protein aggregations clearance, but its effects on NSC activation remains unknown. Here, we show that UCHL1 promotes NSC activation by clearing protein aggregates through ubiquitin-proteasome approach. Upregulation of UCHL1 facilitated the proliferation of spinal cord NSCs after spinal cord injury (SCI). Based on protein microarray analysis of SCI cerebrospinal fluid, it is further revealed that C3+ neurotoxic reactive astrocytes negatively regulated UCHL1 and proteasome activity via C3/C3aR signaling, led to increased abundances of protein aggregations and decreased NSC proliferation. Furthermore, blockade of reactive astrocytes or C3/C3aR pathway enhanced NSC activation post-SCI by reserving UCHL1 and proteasome functions. Together, this study elucidated a mechanism regulating NSC activation in the adult spinal cord involving the UCHL1-proteasome approach, which may provide potential molecular targets and new insights for NSC fate regulation.

Abstract A lipidome comprises thousands of lipid species, many of which are isomers and isobars. Liquid chromatography-tandem mass spectrometry (LC-MS/MS), although widely used for lipidomic profiling, faces challenges in differentiating lipid isomers. Herein, we address this issue by leveraging the orthogonal separation capabilities of hydrophilic interaction liquid chromatography (HILIC) and trapped ion mobility spectrometry (TIMS). We further integrate isomer-resolved MS/MS methods onto HILIC-TIMS, which enable pinpointing double bond locations in phospholipids and sn-positions in phosphatidylcholine. This system profiles phospholipids at multiple structural levels with short analysis time (

Abstract Effective and safe delivery of small interfering RNA (siRNA) by nanomaterials to cancer cells is one of the main challenges in cancer treatment. In this study, we constructed the selenium nanoparticles conjugated with RGDfC (one tumor-targeted polypeptide) to prepare a biocompatible gene vector (RGDfC-SeNPs) and then loaded with siDCBLD2 to synthesize the RGDfC-Se@siDCBLD2 for colorectal cancer (CRC) therapy. As expected, RGDfC-SeNPs could enhance the cellular uptake of siDCBLD2 in human HCT-116 colon cancer cells by targeting polypeptide RGDfC on the surface of colon cancer cells. RGDfC-Se@siDCBLD2 could be effectively internalized by HCT-116 cells mainly through a clathrin-related endocytosis pathway. In addition, RGDfC-Se@siDCBLD2 exhibited high siRNA release efficiency in an acidic tumor environment. Moreover, RGDfC-Se@siDCBLD2 could inhibit the proliferation and induce apoptosis in HCT-116 cells by special silencing gene DCBLD2 expression. RGDfC-Se@siDCBLD2 could be specifically accumulated to the tumor sites and exhibited significantly anti-CRC efficacy on HCT-116 tumor-bearing mice without obvious side effects. Taken together, these results suggest that selenium nanoparticles can be used as an effective gene vector with good biocompatibility, and RGDfC-Se@siDCBLD2 provides a promising strategy for combining tumor-target and siRNA delivery in treating CRC.

Abstract Background Protein engineering aims to improve the functional properties of existing proteins to meet people’s needs. Current deep learning-based models have captured evolutionary, functional, and biochemical features contained in amino acid sequences. However, the existing generative models need to be improved when capturing the relationship between amino acid sites on longer sequences. At the same time, the distribution of protein sequences in the homologous family has a specific positional relationship in the latent space. We want to use this relationship to search for new variants directly from the vicinity of better-performing varieties. Results To improve the representation learning ability of the model for longer sequences and the similarity between the generated sequences and the original sequences, we propose a temporal variational autoencoder (T-VAE) model. T-VAE consists of an encoder and a decoder. The encoder expands the receptive field of neurons in the network structure by dilated causal convolution, thereby improving the encoding representation ability of longer sequences. The decoder decodes the sampled data into variants closely resembling the original sequence. Conclusion Compared to other models, the person correlation coefficient between the predicted values of protein fitness obtained by T-VAE and the truth values was higher, and the mean absolute deviation was lower. In addition, the T-VAE model has a better representation learning ability for longer sequences when comparing the encoding of protein sequences of different lengths. These results show that our model has more advantages in representation learning for longer sequences. To verify the model’s generative effect, we also calculate the sequence identity between the generated data and the input data. The sequence identity obtained by T-VAE improved by 12.9% compared to the baseline model.

Abstract Inorganic sulfide solid-state electrolytes, especially Li6PS5X (X = Cl, Br, I), are considered viable materials for developing all-solid-state batteries because of their high ionic conductivity and low cost. However, this class of solid-state electrolytes suffers from structural and chemical instability in humid air environments and a lack of compatibility with layered oxide positive electrode active materials. To circumvent these issues, here, we propose Li6+xMxAs1-xS5I (M=Si, Sn) as sulfide solid electrolytes. When the Li6+xSixAs1-xS5I (x = 0.8) is tested in combination with a Li-In negative electrode and Ti2S-based positive electrode at 30 °C and 30 MPa, the Li-ion lab-scale Swagelok cells demonstrate long cycle life of almost 62500 cycles at 2.44 mA cm−2, decent power performance (up to 24.45 mA cm−2) and areal capacity of 9.26 mAh cm−2 at 0.53 mA cm−2.

Classical swine fever (CSF), caused by the classical swine fever virus (CSFV), results in significant economic losses to the swine industry in many countries. Vaccination represents the primary strategy to control CSF and the CSFV E2 protein is known as the major protective antigen. However, the E2 protein expressed or presented by different systems elicits distinct immune responses. In this study, we established a stable CHO cell line to express the E2 protein and delivered it using self-assembled ferritin nanoparticles (NPs). Subsequently, we compared the adaptive immune responses induced by the E2-ferritin NPs and the monomeric E2 protein produced by the CHO cells or a baculovirus expression system. The results revealed that the NP-delivered E2 protein elicited higher titers of neutralizing antibodies than did the monomeric E2 protein in pigs. Importantly, only the NP-delivered E2 protein significantly induced CSFV-specific IFN-γ-secreting cells. Furthermore, all the pigs inoculated with the E2-ferritin NPs were completely protected from a lethal CSFV challenge infection. These findings demonstrate the ability of the E2-ferritin NPs to protect pigs against the lethal CSFV challenge by eliciting robust humoral and cellular immune responses.

Ships are important targets for modern naval warfare detection and reconnaissance. The accurate detection of ships contributes to the maintenance of maritime rights and interests and the realisation of naval strategy. Synthetic Aperture Radar (SAR) image detection tasks play a vital role in ship detection, which has consistently been a research hotspot in the field of SAR processing. Although significant progress has been achieved in SAR ship detection techniques using deep learning methods, some challenges still persist. Natural images and SAR images significantly diverge in imaging mechanisms and scattering characteristics. In complex background environments, ships exhibit multiscale variations and dense arrangements, and numerous small-sized ships may be present, culminating in false or missed detections. To address these issues, we propose a novel SAR ship detection network, namely, a Wavelet-Driven Feature-Enhanced Attention–You Only Look Once X (WDFA-YOLOX) network. Firstly, we propose a Wavelet Cascade Residual (WCR) module based on the traditional image processing technique wavelet transform, which is embedded within an improved Spatial Pyramid Pooling (SPP) module, culminating in the formation of the effective wavelet transform-based SPP module (WSPP). The WSPP compensates for the loss of fine-grained feature information during pooling, enhancing the capability of the network to detect ships amidst complex background interference. Secondly, a Global and Local Feature Attention Enhancement (GLFAE) module is proposed, leveraging a parallel structure that combines convolutional modules with transformer modules to reduce the effect of irrelevant information and effectively strengthens valid features associated with small-sized ships, resulting in a reduction in false negatives in small-sized ship detection. Finally, a novel loss function, the Chebyshev distance-generalised IoU loss function, is proposed to significantly enhance both the precision of the detection box and the network convergence speed. To support our approach, we performed thorough experiments on the SSDD and HRSID, achieving an average precision (AP) of 99.11% and 96.20%, respectively, in ship detection. The experimental results demonstrate that WDFA-YOLOX has significant advantages in terms of detection accuracy, generalisation capability, and detection speed and can effectively realise more accurate detection in SAR images, consistently exhibiting superior performance and application value in SAR ship detection.

Background: Progress in cardiovascular health is increasingly concentrated in high-income countries, while the burden of cardiovascular disease (CVD) is high in low - and middle-income countries, a clear health inequity that must be urgently addressed. Objective: This study aims to evaluate the prevalence and clustering of CVD risk factors in the three Lancang-Mekong regions. Methods: We conducted a population-based cross-sectional survey from January 2021 to March 2023 in China, Laos, and Cambodia. We compared the prevalence and clustering of CVD risk factors including hypertension, dyslipidemia, diabetes mellitus, overweight / obesity, current smoker, current drinker, inadequate vegetable and fruit intake, and insufficient physical activity across the three regions, and were further stratified by gender and age. Multivariate logistic regression models were performed to explore factors influencing the aggregation of CVD risk factors (≥2, ≥3, ≥4). Results: A total of 11005 adults were included. Hypertension emerged as the primary metabolic risk factors in Laos (36.8%) and Cambodia (23.5%), whereas overweight / obesity was 37.6% in China. In terms of behavioral risk factors, all three regions showed insufficient vegetable and fruit intake. The prevalence of individuals without CVD risk factors was 10% in China, 1.9% in Laos, and 5.2% in Cambodia. Meanwhile, the prevalence of two or more risk factors was 64.6% in China, 79.2% in Laos, and 76.0% in Cambodia. Multivariate logistic regression models revealed that the propensity for CVD risk factors clustering was higher in men and increased with age in all three countries. Conclusions: CVD risk factors and multiple clustering are pressing health threats among adults in low- and middle-income areas along the Lancang-Mekong River Basin. This study highlights the urgent need for proactive tailored strategies to control CVD risk factors.

A novel storage technique that combines the low-frequency electric field (LFEF) and ice temperature was used to extend the shelf life of Pacific white shrimp (Penaeus vannamei). The study investigated the effect of LFEF treatment on the quality and microbial composition of Penaeus vannamei during storage at ice temperature. The results showed that the LFEF treatment significantly extended the shelf life of shrimp during storage at ice temperature. The total volatile base nitrogen (TVB-N) and pH of samples increased over time, while the total viable count (TVC) showed a trend of first decreasing and then increasing. Obviously, shrimp samples treated with LFEF had a lower pH, TVB-N and TVC values than the untreated samples (p < 0.05) at the middle and late stages of storage. LFEF treatment increased the diversity and altered the composition of the microbial communities in Penaeus vannamei. Additionally, the treatment led to a decrease in the relative abundance of dominant spoilage bacteria, including Aliivibrio, Photobacterium and Moritella, in Penaeus vannamei stored at ice temperature for 11 days. Furthermore, correlation analysis indicated that TVB-N and pH had a significant and positive correlation with Pseudoalteromonas, suggesting that Pseudoalteromonas had a greater impact on shrimp quality. This study supports the practical application of accelerated low-frequency electric field-assisted shrimp preservation as an effective means of maintaining shrimp meat quality.

Highlights Highly performed perovskite solar cells are achieved via introducing organic–inorganic CL–NH complex as multifunctional interfacial layer. CL–NH complex not only reduces oxygen vacancies on the surface of SnO2 but also regulates film crystallization, resulting in a superior device efficiency of 23.69%. The resulting device performs excellent stability with 91.5% initial power conversion efficiency retained after 500 h light illumination.

Abstract Background The early diagnosis of medullary thyroid carcinoma (MTC) is still a challenge in clinical practice. Based on ultrasound features, many MTC cases without suspicious characteristics are not categorized as high risk for malignancy. This study was designed to comprehensively investigate the ultrasonic features of MTC on ultrasound and help identify thyroid nodules with a high risk of MTC. Methods Between 2017 and 2023, we retrospectively reviewed 116 consecutive thyroid nodules with a histologic diagnosis of MTC who had undergone preoperative ultrasound examination. According to the ultrasonic criteria for risk classification, nodules were classified as “ultrasound-high suspicious” (h-MTC) and “ultrasound-low suspicious” (l-MTC). Using the same database, a tumour size- and risk evaluation-matched control group comprising 62 lesions was randomly selected to compare the vascularity features of l-MTC disease. Results We identified 85 h-MTC nodules (73.3%) and 31 l-MTC nodules (26.7%). For patients with l-MTC disease, 22/31 (71.0%) of the lesions were followed up for a period before fine needle aspiration (FNA) or surgery. We observed more penetrating branching vascularity in the l-MTC group than in the benign nodule group (23/31, 74.2% vs. 5/59, 4.8%, P

Abstract The differentiation of pluripotent stem cells (PSCs) into diverse functional cell types provides a promising solution to support drug discovery, disease modeling, and regenerative medicine. However, functional cell differentiation is currently limited by the substantial line-to-line and batch-to-batch variabilities, which severely impede the progress of scientific research and the manufacturing of cell products. For instance, PSC-to-cardiomyocyte (CM) differentiation is vulnerable to inappropriate doses of CHIR99021 (CHIR) that are applied in the initial stage of mesoderm differentiation. Here, by harnessing live-cell bright-field imaging and machine learning (ML), we realize real-time cell recognition in the entire differentiation process, e.g., CMs, cardiac progenitor cells (CPCs), PSC clones, and even misdifferentiated cells. This enables non-invasive prediction of differentiation efficiency, purification of ML-recognized CMs and CPCs for reducing cell contamination, early assessment of the CHIR dose for correcting the misdifferentiation trajectory, and evaluation of initial PSC colonies for controlling the start point of differentiation, all of which provide a more invulnerable differentiation method with resistance to variability. Moreover, with the established ML models as a readout for the chemical screen, we identify a CDK8 inhibitor that can further improve the cell resistance to the overdose of CHIR. Together, this study indicates that artificial intelligence is able to guide and iteratively optimize PSC differentiation to achieve consistently high efficiency across cell lines and batches, providing a better understanding and rational modulation of the differentiation process for functional cell manufacturing in biomedical applications.

Abstract Background X-linked adrenal hypoplasia congenita (AHC) is a rare disorder characterized by primary adrenal insufficiency (PAI) and hypogonadotropic hypogonadism (HH), with limited clinical and genetic characterization. Methods The clinical, biochemical, genetic, therapeutic, and follow-up data of 42 patients diagnosed with X-linked AHC were retrospectively analysed. Results Hyperpigmentation (38/42, 90%), vomiting/diarrhoea (20/42, 48%), failure to thrive (13/42, 31%), and convulsions (7/42, 17%) were the most common symptoms of X-linked AHC at onset. Increased adrenocorticotropic hormone (ACTH) (42/42, 100%) and decreased cortisol (37/42, 88%) were the most common laboratory findings, followed by hyponatremia (32/42, 76%) and hyperkalaemia (29/42, 69%). Thirty-one patients presented with PAI within the first year of life, and 11 presented after three years of age. Three of the thirteen patients over the age of 14 exhibited spontaneous pubertal development, and ten of them experienced delayed puberty due to HH. Six patients receiving human chorionic gonadotropin (hCG) therapy exhibited a slight increase in testicular size and had rising testosterone levels (both P

Abstract Background Inflammation-related predisposition to cancer plays an essential role in cancer progression and is associated with poor prognosis. A hypoxic microenvironment and neutrophil infiltration are commonly present in solid tumours, including gastric cancer (GC). Neutrophil extracellular traps (NETs) have also been demonstrated in the tumour immune microenvironment (TIME), but how NETs affect GC progression remains unknown. Here, we investigated the role of NET formation in the TIME and further explored the underlying mechanism of NETs in GC tumour growth. Methods Hypoxia-induced factor-1α (HIF-1α), citrulline histone 3 (citH3) and CD66b expression in tumour and adjacent nontumor tissue samples was evaluated by western blotting, immunofluorescence and immunohistochemical staining. The expression of neutrophil-attracting chemokines in GC cells and their hypoxic-CM was measured by qRT‒PCR and ELISA. Neutrophil migration under hypoxic conditions was evaluated by a Transwell assay. Pathway activation in neutrophils in a hypoxic microenvironment were analysed by western blotting. NET formation was measured in vitro by immunofluorescence staining. The protumour effect of NETs on GC cells was identified by Transwell, wound healing and cell proliferation assays. In vivo, an lipopolysaccharide (LPS)-induced NET model and subcutaneous tumour model were established in BALB/c nude mice to explore the mechanism of NETs in tumour growth. Results GC generates a hypoxic microenvironment that recruits neutrophils and induces NET formation. High mobility group box 1 (HMGB1) was translocated to the cytoplasm from the nucleus of GC cells in the hypoxic microenvironment and mediated the formation of NETs via the toll-like receptor 4 (TLR4)/p38 MAPK signalling pathway in neutrophils. HMGB1/TLR4/p38 MAPK pathway inhibition abrogated hypoxia-induced neutrophil activation and NET formation. NETs directly induced GC cell invasion and migration but not proliferation and accelerated the augmentation of GC growth by increasing angiogenesis. This rapid tumour growth was abolished by treatment with the NET inhibitor deoxyribonuclease I (DNase I) or a p38 MAPK signalling pathway inhibitor. Conclusions Hypoxia triggers an inflammatory response and NET formation in the GC TIME to augment tumour growth. Targeting NETs with DNase I or HMGB1/TLR4/p38 MAPK pathway inhibitors is a potential therapeutic strategy to inhibit GC progression. Video Abstract

Abstract Effective multi-agent teamwork can be facilitated by using personas to decompose goals into lower-level team subtasks through a shared understanding of multi-agent tasks. However, traditional methods for role discovery and assignment are not scalable and fail to adapt to dynamic changes in the environment. To solve this problem, we propose a new framework for learning dynamic role discovery and assignment. We first introduce an action encoder to construct a vector representation for each action based on its characteristics, and define and classify roles from a more comprehensive perspective based on both action differences and action contributions. To rationally assign roles to agents, we propose a representation-based role selection policy based on consideration of role differences and reward horizons, which enables agents to play roles dynamically by dynamically assigning agents with similar abilities to play the same role. Agents playing the same role share their learning of the role, and different roles correspond to different action spaces. We also introduce regularizers to increase the differences between roles and stabilize training by preventing agents from changing roles frequently. Role selection and role policy integrate action representations and role differences in a restricted action space, improving learning efficiency. We conducted experiments in the SMAC benchmark and showed that our method enables effective role discovery and assignment, outperforming the baseline on four of the six scenarios, with an average improvement in win rate of 20 $$\%$$ % , and is effective in hard and super hard maps. We also conduct ablation experiments to demonstrate the importance of each component in our approach.

Based on conventional observation data, regional station observation data, EC reanalysis data, FY-2G satellite data, and radar data, a downburst in Yichang on 29 July 2017 was analyzed. The results show that: (1) The downburst occurred at the edge of subtropical high, the convection in the north of Yichang was triggered by cold air, and the convection in the central section was triggered by the uplift of mountain terrain in the west of Yichang. (2) the downburst was accompanied by the abrupt rise of air pressure, the sudden drop in air temperature, the sudden change of wind direction, and the sudden increase of wind speed. The strong and rapid cold outflow has the most obvious influence on the occurrence of the gale. (3) Satellite cloud image shows that the location of gale is basically in the area with the largest cloud top brightness temperature gradient in the front of cloud cluster propagation direction. (4) The process is characterized by a typical pulse storm and the initial thunderstorm. The echo intensity is strong, the height is 4~6 km, the echo shape is vertical, and there are obvious radial convergence characteristics in the middle layer about 10 minutes before the surface gale appears. (5) The echo is strengthened twice in the process of moving and developing, one is echo merging enhancement and the other one is strengthened by local thermal and dynamic convergence near the Three Gorges Dam Area, and blocked by the Yangtze River Valley twice and the high blocking effect. The echo moves slowly in the Yangtze River Valley, so it can last for a long time.

Cervical cancer is a typical cancer characterized by abnormal cell growth in the cervical area. Ginkgo biloba L. is a deciduous tree of the genus Ginkgo, possessing anti-cancer effects. The aim of this study was to explore the effect of strain J1 from Ginkgo biloba L. on apoptosis of cervical cancer cells. Bacteriostatic activity test, MTT assay and Flow cytometry were used in this study. Crude extract of J1 fermentation reduced cell growth in cervical cancer. The crude extract of the fermentation broth of strain J1 had a good inhibitory effect on Staphylococcus aureus. The crude extract of the J1 fermentation had no toxic effect on normal WISH cells in the range of anti-cervical cancer concentration. Crude extract of J1 fermentation induced apoptosis and regulated cell cycle in cervical cancer. The active compounds were separated and identified by preparative chromatography, and more than ten compounds were obtained. Our study suggests that the crude extract of J1 fermentation from Endophytic fungi of Ginkgo biloba reduced cell growth, and promoted apoptosis of cervical cancer, and is a potential therapeutic strategy for the treatment of cervical carcinoma.