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Abstract Body composition assessment is very useful for evaluating a patient’s status in the clinic, but recognizing, labeling, and calculating the body compositions would be burdensome. This study aims to develop a web-based service that could automate calculating the areas of skeleton muscle (SM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) according to L3 computed tomography (CT) images. 1500 L3 CT images were gathered from Xuzhou Central Hospital. Of these, 70% were used as the training dataset, while the remaining 30% were used as the validating dataset. The UNet framework was combined with attention gate (AG), Squeeze and Excitation block (SEblock), and Atrous Spatial Pyramid Pooling (ASSP) modules to construct the segmentation deep learning model. The model’s efficacy was externally validated using two other test datasets with multiple metrics, the consistency test and manual result checking. A graphic user interface was also created and deployed using the Streamlit Python package. The custom deep learning model named L3 Body Composition Segmentation Model (L3BCSM) was constructed. The model’s Median Dice is 0.954(0.930, 0.963)(SATA), 0.849(0.774,0.901)(VATA), and 0.920(0.901, 0.936)(SMA), which is equal to or better than classic models, including UNETR and AHNet. L3BCSM also achieved satisfactory metrics in two external test datasets, consistent with the qualified label. An internet-based application was developed using L3BCSM, which has four functional modules: population analysis, time series analysis, consistency analysis, and manual result checking. The body composition assessment application was well developed, which would benefit the clinical practice and related research.

Abstract Embryonic axis formation is essential for patterning and morphogenesis in vertebrates and is tightly regulated by the dorsal organizer. Previously, we demonstrated that maternally derived Huluwa (Hwa) acts as a dorsal determinant, dictating axis formation by activating β-catenin signaling in zebrafish and Xenopus. However, the mechanism of activation and fine regulation of the Hwa protein remains unclear. Through candidate screening we identified a mutation at Ser168 in the PPNSP motif of Hwa that dramatically abolishes its axis-inducing activity. Mechanistically, mutating the Ser168 residue reduced its binding affinity to Tankyrase 1/2 and the degradation of the Axin protein, weakening β-catenin signaling activation. We confirmed that Ser168 is phosphorylated and that phosphorylation increases Hwa activity in β-catenin signaling and axis induction. Several kinases including Cdk16, Cdk2, and GSK3β, were found to enhance Ser168 phosphorylation in vitro and in vivo. Both dominant-negative Cdk16 expression and pHwa (Ser168) antibody treatment reduce Hwa function. Lastly, a knock-in allele mutating Ser168 to alanine resulted in embryos lacking body axes, demonstrating that Ser168 is essential to axis formation. In summary, Ser168 acts as a phosphorylation switch in Hwa/β-catenin signaling for embryonic axis induction, regulated by multiple kinases.

For the control of cord steel inclusion， long time soft bubbling treatment is usually chosen to improve the cleanliness of molten steel， but it will lead to the increased erosion of magnesia-carbon bricks. Through the industrial production test， the effects of soft blowing time after LF refining on the composition and quantity of oxide inclusions of cord steel wire rod were studied by means of FEI Explorer 4 automatic scanning electron microscopy. Becca standard score and Kobe Standard Max-T （ave） score were used to evaluate the inclusion of wire rod. The results showed that the composition of oxide inclusions larger than 3 μm in the wire rod was similar to that in the process of soft blowing time of 45 min and 25 min after LF refining， and the density of inclusions was 135 /100 mm2 and 103 /100 mm2， respectively. The density of inclusions in the process of soft blowing time of 25 min after LF refining was slightly lower. Expanding the number of comparison tests， the score of Kobe standard Max-T （ave） and Becca standard indicate that the inclusions control of soft bubbling process for 20-25 min did not become worse or slightly improved. The control of low melting point inclusions in cord steel was mainly through controlling Al content， refining slag and other process parameters， and the inclusions that lead to the failure of the final product are often inconsistent with the types of endogenous inclusions. For cord steel， it can be considered to reduce the soft blowing time after LF refining.

High-entropy fluorite oxides (HEFOs) show significant potential for thermal protection applications due to their advantageous combination of low thermal conductivity and high Yong’s modulus. However, the factors influencing its formation have not been well studied, and a systematic method for compositional design has not yet been established. In this paper, the effects of oxygen vacancy concentration (Ovac) and mean cation radius (r¯) on formability of HEFOs were investigated to develop a compositional design approach. The results indicate that an appropriate r¯ and Ovac is crucial for promoting the formability of single-phase (CaxCey1Zry2HfzSnzTiz)O2−δ HEFOs. High mass/size disorder and an appropriate Ovac (10%) result in (Ca0.2Ce0.14Zr0.12Hf0.18Sn0.18Ti0.18)O2−δ exhibiting the lowest thermal conductivity of 1.24 W·m−1·K−1. Building upon these insights and employing a valence combination strategy, three new single-phase HEFOs with low thermal conductivity were successfully designed and synthesized, namely, (La0.28Y0.28Ce0.18Zr0.18W0.08)O2−δ, (La0.3Y0.3Ce0.2Nb0.1Ta0.1)O2−δ, and (Yb0.52Ce0.12Zr0.12Sn0.12Nb0.12)O2−δ. This design approach will provide a valuable reference for the design of other high-entropy oxides.

Abstract Acute anterior uveitis (AAU) is a common extra‐articular manifestation of ankylosing spondylitis (AS), particularly in patients positive for the human leucocyte antigen (HLA)‐B27 genetic marker. To explore the underlying mechanisms of HLA‐B27+ AS‐associated AAU, we employed single‐cell RNA sequencing to profile the transcriptomes of peripheral blood mononuclear cells in three HLA‐B27+ AS‐associated AAU patients and three healthy controls (HCs). We identified 11 distinct immune cell clusters, with a particular focus on monocytes, revealing six subsets, including three previously unidentified subsets, namely, GTPase immune‐associated proteins, Th17‐related, and lncRNA monocytes, with unique gene expression patterns. Significant differences in monocyte composition, activation states, and gene expression were observed between patients and HCs, particularly within HLA monocyte subpopulations. Notably, enhanced expression of X‐inactive specific transcript and myeloid cell nuclear differentiation antigen genes was validated across monocyte subclusters in patients. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis highlighted significant enrichment in antigen processing and presentation pathways, shedding light on the disease's molecular mechanisms. These findings provide novel insights into the molecular mechanisms of HLA‐B27+ AS‐associated AAU and may contribute to the development of targeted diagnostic and therapeutic strategies. Further clinical validation is essential.

BackgroundGlioma is a highly heterogeneous malignancy of the central nervous system. This heterogeneity is driven by various molecular processes, including neoplastic transformation, cell cycle dysregulation, and angiogenesis. Among these biomolecular events, inflammation and stress pathways in the development and driving factors of glioma heterogeneity have been reported. However, the mechanisms of glioma heterogeneity under stress response remain unclear, especially from a spatial aspect.MethodsThis study employed single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) to explore the impact of oxidative stress response genes in oligodendrocyte precursor cells (OPCs). Our analysis identified distinct pathways activated by oxidative stress in two different types of gliomas: high- and low- grade (HG and LG) gliomas.ResultsIn HG gliomas, oxidative stress induced a metabolic shift from oxidative phosphorylation to glycolysis, promoting cell survival by preventing apoptosis. This metabolic reprogramming was accompanied by epithelial-to-mesenchymal transition (EMT) and an upregulation of stress response genes. Furthermore, SCENIC (Single-Cell rEgulatory Network Inference and Clustering) analysis revealed that oxidative stress activated the AP1 transcription factor in HG gliomas, thereby enhancing tumor cell survival and proliferation.ConclusionOur findings provide a novel perspective on the mechanisms of oxidative stress responses across various grades of gliomas. This insight enhances our comprehension of the evolutionary processes and heterogeneity within gliomas, potentially guiding future research and therapeutic strategies.

Abstract The development of in situ techniques to quantitatively characterize the heterogeneous reactions is essential for understanding physicochemical processes in aqueous phase. In this work, a new approach coupling in situ UV–vis spectroscopy with a two‐step algorithm strategy is developed to quantitatively monitor heterogeneous reactions in a compact closed‐loop incorporation. The algorithm involves the inverse adding‐doubling method for light scattering correction and the multivariate curve resolution‐alternating least squares (MCR‐ALS) method for spectral deconvolution. Innovatively, theoretical spectral simulations are employed to connect MCR‐ALS solutions with chemical molecular structural evolution without prior information for reference spectra. As a model case study, the aqueous adsorption kinetics of bisphenol A onto polyamide microparticles are successfully quantified in a one‐step UV–vis spectroscopic measurement. The practical applicability of this approach is confirmed by rapidly screening a superior adsorbent from commercial materials for antibiotic wastewater adsorption treatment. The demonstrated capabilities are expected to extend beyond monitoring adsorption systems to other heterogeneous reactions, significantly advancing UV–vis spectroscopic techniques toward practical integration into automated experimental platforms for probing aqueous chemical processes and beyond.

Abstract This study aimed to investigate the impact of tactical formations on the physical and technical performance of professional football players in the Chinese Super League (CSL). A sample of 800 games from the 2015–2021 CSL was analyzed, and players' physical (total distance covered, distance covered while ball in play, number of sprints, sprint distance, and high/middle/low-speed running) and technical (gain/loss of possession, ball retention percentage, challenges, challenge success percentage, passes, and pass success percentage) performance was assessed across six team formations: 3-5-2 (n = 137), 4-3-3 (n = 77), 4-2-3-1 (n = 391), 4-4-2 (n = 257), 3-4-3 (n = 41), and 4-1-4-1 (n = 107). Linear mixed models were used to assess variations in performance indicators across positions and formations. The results demonstrated that central defenders traveled significantly more total and low-speed running distances in the 3-5-2 formation than in the 4-2-3-1 formation (ES range: 0.33–0.34, p

Abstract Purpose The health of rhizosphere soil microorganisms is an important indicator to evaluate soil quality. Therefore, understanding the response of rhizosphere soil microorganisms to tobacco crop succession is crucial for promoting the sustainable development of agriculture. Methods The microbial diversity and community structure of rhizosphere soil in continuous cropping and non-cropped tobacco for 7 years were analyzed by the Illumina platform. Result (1) Continuous cropping tobacco cause rhizosphere soil acidification and reduction in alkaline nitrogen (AN) and soil organic matter (SOM). (2) Continuous cropping tobacco reduces the diversity of rhizosphere soil microbial communities, increasing harmful functional microorganisms and declining beneficial ones. (3) The abundance of bacteria that perform nitrification and saprophytic fungi in the rhizosphere soil of continuous cropping areas decreases, inhibiting carbon and nitrogen cycling processes. (4) The composition and diversity of the soil rhizosphere microbial community are affected by the imbalance in the physicochemical property of the rhizosphere. Conclusion Continuous cropping tobacco cause rhizosphere soil acidification and nutrient imbalance, and the carbon and nitrogen cycles involved in microorganisms were damaged. Furthermore, the decreased diversity of rhizosphere soil microorganisms and the increased abundance of pathogenic fungi contribute to the continuous cropping obstacles of tobacco.

IntroductionGlioma, a prevalent and deadly brain tumor, is marked by significant cellular heterogeneity and metabolic alterations. However, the comprehensive cell-of-origin and metabolic landscape in high-grade (Glioblastoma Multiforme, WHO grade IV) and low-grade (Oligoastrocytoma, WHO grade II) gliomas remains elusive.MethodsIn this study, we undertook single-cell transcriptome sequencing of these glioma grades to elucidate their cellular and metabolic distinctions. Following the identification of cell types, we compared metabolic pathway activities and gene expressions between high-grade and low-grade gliomas.ResultsNotably, astrocytes and oligodendrocyte progenitor cells (OPCs) exhibited the most substantial differences in both metabolic pathways and gene expression, indicative of their distinct origins. The comprehensive analysis identified the most altered metabolic pathways (MCPs) and genes across all cell types, which were further validated against TCGA and CGGA datasets for clinical relevance.DiscussionCrucially, the metabolic enzyme phosphodiesterase 8B (PDE8B) was found to be exclusively expressed and progressively downregulated in astrocytes and OPCs in higher-grade gliomas. This decreased expression identifies PDE8B as a metabolism-related oncogene in IDH-mutant glioma, marking its dual role as both a protective marker for glioma grading and prognosis and as a facilitator in glioma progression.

Abstract Background Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder that affects individuals across their lifespan. Early diagnosis and intervention are crucial for improving outcomes. However, current diagnostic methods are often time-consuming, and costly, making them inaccessible to many families. In the current study, we aim to test caregiver-child interaction as a potential tool for screening children with ASD in clinic. Methods We enrolled 85 preschool children (Mean age: 4.90 ± 0.65 years, 70.6% male), including ASD children with or without developmental delay (DD), and typical development (TD) children, along with their caregivers. ASD core symptoms were evaluated by Childhood Autism Rating Scale (CARS) and Autism Diagnostic Observation Schedule-Calibrated Severity Scores (ADOS-CSS). Behavioral indicators were derived from video encoding of caregiver-child interaction, including social involvement of children (SIC), interaction time (IT), response of children to social cues (RSC), time for caregiver initiated social interactions (GIS) and time for children initiated social interactions (CIS)). Power spectral density (PSD) values were calculated by EEG signals simultaneously recorded. Partial Pearson correlation analysis was used in both ASD groups to investigate the correlation among behavioral indicators scores and ASD symptom severity and PSD values. Receiver operating characteristic (ROC) analysis was used to describe the discrimination accuracy of behavioral indicators. Results Compared to TD group, both ASD groups demonstrated significant lower scores of SIC, IT, RSC, CIS (all p values

Abstract Proper subcellular localization is crucial for the functioning of biomacromolecules, including proteins and RNAs. Nuclear transport is a fundamental cellular process that regulates the localization of many macromolecules within the nuclear or cytoplasmic compartments. In humans, approximately 60 proteins are involved in nuclear transport, including nucleoporins that form membrane-embedded nuclear pore complexes, karyopherins that transport cargoes through these complexes, and Ran system proteins that ensure directed and rapid transport. Many of these nuclear transport proteins play additional and essential roles in mitosis, biomolecular condensation, and gene transcription. Dysregulation of nuclear transport is linked to major human diseases such as cancer, neurodegenerative diseases, and viral infections. Selinexor (KPT-330), an inhibitor targeting the nuclear export factor XPO1 (also known as CRM1), was approved in 2019 to treat two types of blood cancers, and dozens of clinical trials of are ongoing. This review summarizes approximately three decades of research data in this field but focuses on the structure and function of individual nuclear transport proteins from recent studies, providing a cutting-edge and holistic view on the role of nuclear transport proteins in health and disease. In-depth knowledge of this rapidly evolving field has the potential to bring new insights into fundamental biology, pathogenic mechanisms, and therapeutic approaches.

The retinal pigment epithelium (RPE) and choroid are located behind the human retina and have multiple functions in the human visual system. Knowledge of the RPE and choroid cells and their gene expression profiles are fundamental for understanding retinal disease mechanisms and therapeutic strategies. Here, we sequenced the RNA of about 0.3 million single cells from human RPE and choroids across two regions and seven ages, revealing regional and age differences within the human RPE and choroid. Cell–cell interactions highlight the broad connectivity networks between the RPE and different choroid cell types. Moreover, the transcription factors and their target genes change during aging. The coding of somatic variations increases during aging in the human RPE and choroid at the single-cell level. Moreover, we identified ELN as a candidate for improving RPE degeneration and choroidal structure during aging. The mapping of the molecular architecture of the human RPE and choroid improves our understanding of the human vision support system and offers potential insights into the intervention targets for retinal diseases.

Range adaptation refers to the representation of a stimulus value based on its relative position in the range of pre-experienced values. Altered range adaptation in value representation may be related to motivation and pleasure (MAP) deficit in schizophrenia (SCZ). This follow-up study examined the relationship between range adaptation performance and MAP symptoms in SCZ patients. We recruited 26 schizophrenia patients and followed them for 1 year. They completed an experimental task for estimating their range adaptation to outcome value (OV) and expected value (EV) at baseline and after 1 year. At baseline, we found a marginally significant and negative correlation between OV adaptation and avolition symptoms in SCZ patients. Moreover, the 1-year change of EV adaptation was significantly and negatively correlated with the change of self-report pleasure experience. Our results suggest that range adaptation may track the variations of MAP symptoms in SCZ.

This study aimed to investigate the non-linear evolution of position-specific physical and technical performance indicators across different tactical formations in the Chinese Super League (CSL) from the 2015 to the 2021 seasons. Match data were collected from 800 games played in six common formations (3-5-2, 4-3-3, 4-2-3-1, 4-4-2, 3-4-3, and 4-1-4-1). Players were classified into five positions: central defenders (CD; match observations = 2,219), fullbacks (FB; match observations = 2,060), central midfielders (CM; match observations = 2,786), wide midfielders (WM; match observations = 1,587), and forwards (FW; match observations = 1,680). Generalized additive models (GAMs) were constructed to analyze the nonlinear evolution trends in position-specific physical and technical performance across seasons and formations. The results showed that the total distance covered by CDs in the 3-5-2 formation showed a non-linear upward trend from the 2015 to 2021 seasons (R2 = 0.3, p = 0.006); FBs in the 3-4-3, 4-1-4-1, and 3-5-2 formations exhibited non-linear upward trends in number of sprints and sprint distance from the 2015 to 2021 seasons (R2 = 0.189-0.448; P < 0.03, respectively); the high-speed running of FWs in the 4-2-3-1 formation displayed a non-linear decline trend from the 2015 to 2021 seasons (R2 = 0.477; P < 0.001); CMs in the 4-2-3-1 formation demonstrated a non-linear increasing trend in the ball retention percentage (R2 = 0.369; p = 0.001); WMs in the 4-4-2 formation showed a non-linear decreasing trend in ball retention percentage and passes from the 2015 to 2021 seasons (R2 = 0.259-0.29; P = 0.006, respectively). These findings revealed non-linear evolutionary trends in physical and technical performances across positions and formations, providing an in-depth understanding of the changing match demands placed on players during matches. This enables the optimization of training and tactics by developing targeted strategies tailored to meet the specific requirements of different formations and playing positions.

The compositions of water extract (WE) and crude theabrownin (TB) extract from ripe Pu-erh tea prepared by controlled fermentation were analyzed by Curie point pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS) and high performance liquid chromatography (HPLC) and their regulatory effects on obesity in rats were investigated. SD rats were divided into four groups, namely normal diet, high-fat diet, WE and TB. After gavage for 16 weeks, growth indexes, and serum biochemical indexes, oxidative stress and inflammation indexes were analyzed, and histopathological examination of liver tissues was performed by hematoxylin-eosin (HE) and oil red O staining. Results showed that theabrownin, protein and polysaccharide accounted for a large proportion in WE and crude TB. There were significant differences in the contents of catechin and its derivatives such as gallic acid (GA), epicatechin (EC) and epicatechin gallate (EGCG) between WE and crude TB extract (P < 0.05). The contents of the alkaloids caffeine and theobromine in WE were significantly higher than those in TB (P < 0.05). Seven and 12 compounds were shared by the Curie-point pyrolysis products of WE and TB at 380 and 600 ℃, respectively. In the four samples, the number of phenolic compounds was largest, and caffeine was the most abundant compound. Compared with the high-fat model group, the body mass and Lee’s index of the rats from the WE and TB groups significantly decreased (P < 0.05), and so did the levels of serum triglyceride (TG), serum fasting blood glucose (FBG), liver triglyceride and cholesterol (TC) ( P < 0.05), Moreover, fat accumulation was reduced, the levels of serum superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), nuclear factor E2 related factor 2 (Nrf2), interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) were lowered significantly (P < 0.05). These findings indicate increased antioxidant activity and decreased inflammatory factor levels. Furthermore, histological observations of liver sections showed reduction in steatosis, the number of adipocytes and lipid droplet aggregation. To sum up, the compositions of WE and TB were significantly different; however, both showed a positive effect on mass loss and blood lipid reduction. This study can provide a theoretical basis for the deep processing of tea resources and the development of functional products.

Human papillomavirus (HPV) is a prevalent cause of mucosal and cutaneous infections and underlying conditions ranging from benign warts to anogenital and oropharyngeal cancers affecting both males and females, notably cervical cancer. Cervical cancer is the fourth leading cause of cancer deaths among women globally and is the most impactful in low- and middle-income countries (LMICs), where the costs of screening and licensed L1-based HPV vaccines pose significant barriers to comprehensive administration. Additionally, the licensed L1-based HPV vaccines fail to protect against all oncogenic HPV types. This study generated three independent lots of an L2-based target antigen (LBTA), which was engineered from conserved linear L2-protective epitopes (aa11–88) from five human alphapapillomavirus genotypes in E. coli under cGMP conditions and adjuvanted with aluminum phosphate. Vaccination of rabbits with LBTA generated high neutralizing antibody titers against all 17 HPV types tested, surpassing the nine types covered by Gardasil®9. Passive transfer of naïve mice with LBTA antiserum revealed its capacity to confer protection against vaginal challenge with all 17 αHPV types tested. LBTA shows stability at room temperature over >1 month. Standard in vitro and in vivo toxicology studies suggest a promising safety profile. These findings suggest LBTA’s promise as a next-generation vaccine with comprehensive coverage aimed at reducing the economic and healthcare burden of cervical and other HPV+ cancers in LMICs, and it has received regulatory approval for a first-in-human clinical study (NCT05672966).

The global football market has grown in the past three decades, and football clubs' sustainable financial operations have gradually gained attention. This study aims to construct a financial risk assessment model applicable to the football industry, explore globally listed football clubs' overall financial operating characteristics, and analyse the leading causes of the club's financial crisis. We selected a sample of 24 currently listed football clubs worldwide and an exploratory factor analysis (EFA) model to construct the model of financial risk assessment for football clubs. The model identified and classified the financial risk components for listed football clubs, thus facilitating risk warning and prevention for modern professional clubs. This study found that football clubs are at higher financial risk overall, with the following general characteristics: (1) small amount of listed capital; (2) high asset-liability ratio; (3) low net profits and a large proportion of clubs make losses; and (4) weak asset liquidity. Finally, the study discussed the leading causes of the financial crises of football clubs in both external and internal dimensions, providing a reference for the self-sustainability of clubs and football authorities.

Abstract Background To evaluate the possibilty of preventing recurrent vitreous hemorrhage (RVH) after vitrectomy in proliferative diabetic retinopathy (PDR) patients with unabsorbed vitreous hemorrhage (VH) by intravitreal injection of viscoelastic agent (VA) at the end of the surgery and compared its effect with triamcinolone acetonide (TA). Methods This was a pilot prospective, observational study. PDR patients with VH who underwent vitrectomy were assigned to 3 groups according to the tamponade applicated at the end of the surgery, including VA group (intravitreally injected 1 ml VA if the retina was prone to bleed during the operation), TA group (intravitreally injected 2 mg TA when there was much exudates), or balanced salt solution (BSS) group (no tamponade). Then postoperative follow-up was performed routinely until 6 months after surgery. The primary outcome was the incidence of RVH, secondary outcome were the best-corrected visual acuity (BCVA) and introcular pressure (IOP). Cataract formation and other complication were also assessed. Results A total of 68 eyes, from 68 patients, were included. 18,18,32 eyes were enrolled in the VA group, TA group and BSS group, respectively. The integral incidence of RVH after vitrectomy was 5.6%, 5.6% and 12.5% respectively (P = 0.602). There was no early RVH in VA or TA group, whereas 3 early RVHs were identified in BSS group, however there was no significant difference (P = 0.171). Every group had one late RVH case. In all groups, final BCVA showed significant improvement compared to baseline. BCVA at any postoperative visit showed no significant differences among 3 groups. Mean IOP was higher 1 week after surgery in VA group compared with the other groups; however, in other times the differences were not significant. No cataract formation and other complication was noted in 3 groups. Conclusion Intravitreal injection of VA or TA at the end of vitrectomy for PDR patients with unabsorbed VH tend to reduce the incidence of early RVH after vitrectomy similarly. As VA was preferred to applicate in the eyes that were prone to bleed, intravitreal injection of VA at the end of vitrectomy might be a promising method for preventing RVH in PDR patients.

Abstract Background Recent studies have shown that the fox family plays a vital role in tumorigenesis and progression. Forkhead Box S1 (FOXS1), as a newly identified subfamily of the FOX family, is overexpressed in certain types of malignant tumors and closely associated with patient's prognosis. However, the role and mechanism of the FOXS1 in colorectal cancer (CRC) remain unclear. Method FOXS1 level in CRC tissues and cell lines was analyzed by western blot and quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemistry (IHC) was used to detect the relationship between FOXS1 expression and clinicopathological features in 136 patients in our unit. The expression of FOXS1 was knocked down in CRC cells using small interfering RNA (siRNA) technology. Cell proliferation was assessed by CCK8 assay, colony formation, and 5-Ethynyl-20-deoxyuridine (EdU) incorporation assay. Flow cytometry detected apoptosis and wound healing, and Transwell assays determined cell migration and invasion. Western blotting was used to detect the levels of proteins associated with the Wnt/β-catenin signaling pathway. Then, we used short hairpin RNA (shRNA) to knock down FOXS1 to see the effect of FOXS1 on the proliferation, migration, invasion, and metastasis of CRC cells in vivo. Finally, we investigated the impact of Wnt activator LiCl on the proliferation, migration, invasion, and metastasis of CRC cells after FOXS1 knockdown. Result Compared to those in normal groups, FOXS1 overexpressed in CRC tissues and CRC cells (P

In recent years, there has been an increase in the scientific production of youth soccer. However, a panoramic map of research on this subject does not exist. The aim of this study was to identify global research trends in youth soccer over time, among the main levels of analysis: sources, authors, documents, and keywords. The bibliometric software Biblioshiny was used to analyze 2606 articles in Web of Science (WoS) published between 2012 and 2021. The main conclusion is that US and UK scholars dominate the research; the topics of research are changing with the real needs, and research on the topic of performance has been of interest to scholars; talent identification and development, performance, injury prevention, and concussion are the studies of interest to scholars in this area. This finding, which offers a global picture of youth soccer research over time, can help future research in this or similar domains.

The classification of fish species has important practical significance for both the aquaculture industry and ordinary people. However, existing methods for classifying marine and freshwater fishes have poor feature extraction ability and do not meet actual needs. To address this issue, we propose a novel method for multi-water fish classification (Fish-TViT) based on transfer learning and visual transformers. Fish-TViT uses a label smoothing loss function to solve the problem of overfitting and overconfidence of the classifier. We also employ Gradient-weighted Category Activation Mapping (Grad-CAM) technology to visualize and understand the features of the model and the areas on which the decision depends, which guides the optimization of the model architecture. We first crop and clean fish images, and then use data augmentation to expand the number of training datasets. A pre-trained visual transformer model is used to extract enhanced features of fish images, which are subsequently cropped into a series of flat patches. Finally, a multi-layer perceptron is used to predict fish species. Experimental results show that Fish-TViT achieves high classification accuracy on both low-resolution marine fish data (94.33%) and high-resolution freshwater fish data (98.34%). Compared with traditional convolutional neural networks, Fish-TViT has better performance.

This work studied the wind load acting on a point focus solar furnace composed of a 110 m2 heliostat and a 77 m2 concentrator through wind tunnel testing. Based on wind tunnel test data under 305 different working conditions, the variation laws of the wind pressure coefficient, power spectral density, and wind load coefficient of the heliostat and concentrator were analyzed. The results showed that due to the interaction between the concentrator and heliostat, the wind speed near the heliostat and concentrator decreased but the turbulence intensity increased, which caused the peak wind load coefficient to rise slightly. The results suggested that a safety factor of 1.1–1.2 should be considered for structural design and optimization of solar furnaces.

Capacitive deionization (CDI) is a promising technique for brackish water desalination. However, its salt electrosorption capacity is insufficient for practical application yet, and little information is available on hardness ion (Mg2+, Ca2+) removal in CDI. Herein, hierarchical porous carbon (HPC) was prepared from low-cost and renewable microalgae via a simple one-pot approach, and both MnO2/HPC and polyaniline/HPC (PANI/HPC) composites were then synthesized using a facile, one-step hydrothermal method. Compared with the MnO2 electrode, the MnO2/HPC electrode presented an improved hydrophilicity, higher specific capacitance, and lower electrode resistance. The electrodes exhibited pseudocapacitive behaviors, and the maximum salt electrosorption capacities of MnO2/HPC-PANI/HPC CDI cell was up to 0.65 mmol g−1 NaCl, 0.71 mmol g−1 MgCl2, and 0.76 mmol g−1 CaCl2, respectively, which were comparable and even higher than those of the previously reported CDI cells. Additionally, the MnO2/HPC electrode presented a selectivity order of Ca2+ ≥ Mg2+ > Na+, and the divalent cation selectivity was found to be attributed to their stronger binding strength in the cavity of MnO2. Multiscale simulations further reveal that the MnO2/HPC electrodes with the unique luminal configuration of MnO2 and HPC as supportive framework could offer a great intercalation selectivity of the divalent cations and exhibit a great promise in hardness ion removal.

Abstract Critical coronavirus disease 2019 (COVID-19) is associated with high mortality and potential genetic factors have been reported to be involved in the development of critical COVID-19. We performed a genome-wide association study to identify the genetic factors responsible for developing critical COVID-19. 632 critical patients with COVID-19 and 3021 healthy controls from the Chinese population were recruited. First, we identified a genome-wide significant difference of IL-6 rs2069837 (p = 9.73 × 10−15, OR = 0.41) between 437 critical patients with COVID-19 and 2551 normal controls in the discovery cohort. When replicated these findings in a set of 195 patients with critical COVID-19 and 470 healthy controls, we detected significant association of rs2069837 with COVID-19 (p = 8.89 × 10−3, OR = 0.67). This variant surpassed the formal threshold for genome-wide significance (combined p = 4.64 × 10−16, OR = 0.49). Further analysis revealed that there was a significantly stronger expression of IL-6 in the serum from patients with critical COVID-19 than in that from patients with asymptomatic COVID-19. An in vitro assay showed that the A to G allele changes in rs2069837 within IL-6 obviously decreased the luciferase expression activity. When analyzing the effect of this variant on the IL-6 in the serum based on the rs2069837 genotype, we found that the A to G variation in rs2069837 decreased the expression of IL-6, especially in the male. Overall, we identified a genetic variant in IL-6 that protects against critical conditions with COVID-19 though decreasing IL-6 expression in the serum.

Müller cell is the most abundant glial cell in mammalian retina, supporting the functions of photoreceptors and other retinal neurons via maintaining environmental homeostasis. In response to injury and/or neuronal degeneration, Müller cells undergo morphological and functional alternations, known as reactive gliosis documented in multiple retinal diseases, including age-related macular degeneration (AMD), retinitis pigmentosa, diabetic retinopathy, and traumatic retinal detachment. But the functional consequences of Müller glia cell reactivation or even the regulatory networks of the retinal gliosis are still controversial. In this study, we reveal different subpopulations of Müller cells with distinct metabolic-mitochondrial signatures by integrating single cell transcriptomic data from Early AMD patients and healthy donors. Our results show that a portion of Müller cells exhibits low mitochondrial DNA (mtDNA) expressions, reduced protein synthesis, impaired homeostatic regulation, decreased proliferative ability but enhanced proangiogenic function. Interestingly, the major alternation of Müller cells in Early AMD retina is the change of subpopulation abundance, rather than generation of new subcluster. Transcription factor enrichment analysis further highlights the key regulators of metabolic-mitochondrial states of Müller glias in Early AMD patients especially. Our study demonstrates new characteristics of retinal gliosis associated with Early AMD and suggests the possibility to prevent degeneration by intervening mitochondrial functions of Müller cells.

We evaluated the immunogenicity and protective ability of a chimpanzee replication-deficient adenovirus vectored COVID-19 vaccine (BV-AdCoV-1) expressing a stabilized pre-fusion SARS-CoV-2 spike glycoprotein in golden Syrian hamsters. Intranasal administration of BV-AdCoV-1 elicited strong humoral and cellular immunity in the animals. Furthermore, vaccination prevented weight loss, reduced SARS-CoV-2 infectious virus titers in the lungs as well as lung pathology and provided protection against SARS-CoV-2 live challenge. In addition, there was no vaccine-induced enhanced disease nor immunopathological exacerbation in BV-AdCoV-1-vaccinated animals. Furthermore, the vaccine induced cross-neutralizing antibody responses against the ancestral strain and the B.1.617.2, Omicron(BA.1), Omicron(BA.2.75) and Omicron(BA.4/5) variants of concern. These results demonstrate that BV-AdCoV-1 is potentially a promising candidate vaccine to prevent SARS-CoV-2 infection, and to curtail pandemic spread in humans.

Multiple myeloma (MM) accounts for ~10% of all haematologic malignancies. Little is known about high intratumour heterogeneities in patients stratified by the Revised International Staging System (R-ISS). Herein, we constructed a single-cell transcriptome atlas to compare differential expression patterns among stages. We found that a novel cytotoxic plasma cell (PC) population exhibited with NKG7 positive was obviously enriched in stage II patients. Additionally, a malignant PC population with significantly elevated expression of MKI67 and PCNA was associated with unfavourable prognosis and Epstein-Barr virus (EBV) infection in our collected samples. Moreover, ribonucleotide reductase regulatory subunit M2 (RRM2) was found and verified to promote proliferation of MM cell lines, suggesting RRM2 may serve as a detrimental marker in MM. The percentages of CD8+ T cells and NKT cells decreased along with R-ISS stages, reflecting the plasticity of the tumour immune microenvironment. Importantly, their crosstalks with myeloid cells and PC identified several potential immunotargets such as SIRPA-CD47 and CD74-MIF, respectively. Collectively, this study provided an R-ISS-related single-cell MM atlas and revealed the clinical significance of novel PC clusters, as well as potential immunotargets in MM progression.

Activation of nodal genes is critical for mesoderm and endoderm induction. Our previous study reported that zebrafish nodal genes ndr1/squint and ndr2/cyclops are coordinately regulated by maternal Eomesa, Hwa-activated β-catenin (Hwa/β-catenin) signaling, and Nodal autoregulation (Nodal/Smad2) signaling. However, the exact contribution and underlying mechanisms are still elusive. Here, we applied “causal inference” to evaluate the causal between the independent and dependent variables, and we found that Hwa/β-catenin and Smad2 are the cause of ndr1 activation, while Eomesa is the cause of ndr2 activation. Mechanistically, the different cis-regulatory regions of ndr1 and ndr2 bound by Eomesa, β-catenin, and Smad2 were screened out via ChIP-qPCR and verified by the transgene constructs. The marginal GFP expression driven by ndr1 transgenesis could be diminished without both maternal Eomesa and Hwa/β-catenin, while Eomesa, not β-catenin, could bind and activate ndr2 demonstrated by ndr2 transgenesis. Thus, the distinct regulation of ndr1/ndr2 relies on different cis-regulatory regions.

This article discusses a study conducted on a Chinese population that explores the association between genetic variants and the severity of COVID-19 in critical patients. The researchers identified several specific genetic variants that are significantly associated with the severity of the disease. These findings contribute to a better understanding of the genetic factors influencing COVID-19 severity and may aid in preventing and controlling the disease. Additionally, a document is provided that lists various scientific research articles on the genetic factors influencing COVID-19 susceptibility and severity. These studies include diverse populations from different regions and aim to provide insights into the genetic basis of COVID-19 and its impact on different populations. [Extracted from the article]

Purpose: Age-related macular degeneration (AMD) is a leading cause of vision loss. A Previous study based on the co-localization analysis of the genome-wide association study (GWAS) and eQTL genetic signals have reported that single nucleotide polymorphisms (SNPs), including rs760975, rs11528744, rs3761159, rs7212510, rs6965458, rs7559693, rs56108400, rs28495773, rs9928736, rs11777697, rs4381465 are associated with AMD in Americans. The aim of this study was to investigate the association of these SNPs in a Han Chinese population.Methods: There were 576 patients with wet AMD and 572 healthy controls collected in this study. All SNPs were genotyped by flight mass spectrum. Hardy–Weinberg equilibrium was applied to evaluate allele distributions for both AMD and control groups. The genotype and allele frequencies were evaluated using the χ2 tests. Odds ratio (OR) and 95% confidence intervals (95% CI) were calculated for the risk of genotype and allele.Results: Three of the 11 SNPs (rs11528744 in HTRA1, rs9928736 in BCRA1 and rs4381465 in B3GLCT) were found to be significantly associated with AMD in the allelic model (corrected p = 0.001, OR = 1.391, 95%CI = 1.179–1.640 for rs11528744; corrected p = 0.004, OR = 0.695, 95%CI = 0.544–0.888 for rs9928736; corrected p = 0.002, OR = 0.614, 95%CI = 0.448–0.841 for rs4381465). There were no differences for the remaining eight SNPs between AMD cases and healthy controls.Conclusion: Our results showed that HTRA1 rs11528744, BCRA1 rs9928736, and B3GLCT rs4381465 were associated with wet AMD, suggesting that HTRA1, BCRA1, and B3GLCT genes may be involved in the development of AMD.

AIM: To systematically understand the genetic association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and primary open angle glaucoma (POAG). METHODS: A comprehensive literature search in Google Scholar, PubMed, Science Citation Index, Foreign Medical Literature Retrieval Service, Chinese National Knowledge Infrastructure and Wanfang Databases was performed to collect all eligible studies up to August 2019. Study selection, data abstraction and study quality evaluation were performed by two independent investigators. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association. RESULTS: Eighteen case-control studies including 2156 cases and 2201 controls were identified. There was no significant difference in the terms of MTHFR C677T polymorphism and POAG in the Caucasian population (for T vs C OR=1.11, 95%CI: 0.88 to 1.39; for TT vs CC OR=1.01, 95%CI: 0.76 to 1.36; for TT+TC vs CC OR=1.15, 95%CI: 0.84 to 1.58 and for TT vs TC+CC OR=1.02, 95%CI: 0.78 to 1.33). However, a significant effect was revealed in the Asian population (for T vs C OR=1.34, 95%CI: 1.12 to 1.59; for TT+TC vs CC OR=1.41, 95%CI: 1.14 to 1.76). CONCLUSION: Based on 18 eligible studies, we provide a correlation between MTHFR C677T polymorphism and POAG among the Asians subgroup indicating that the T allele or TT +TC genotype may play a critical role in POAG development in Asians.

Abstract The 2019 coronavirus disease (COVID-19) outbreak caused by the SARS-CoV-2 virus is an ongoing global health emergency. However, the virus’ pathogenesis remains unclear, and there is no cure for the disease. We investigated the dynamic changes of blood immune response in patients with COVID-19 at different stages by using 5’ gene expression, T cell receptor (TCR), and B cell receptors (BCR) V(D)J transcriptome analysis at a single-cell resolution. We obtained single-cell mRNA sequencing (scRNA-seq) data of 341,420 peripheral blood mononuclear cells (PBMCs) and 185,430 clonotypic T cells and 28,802 clonotypic B cells from 25 samples of 16 patients with COVID-19 for dynamic studies. In addition, we used three control samples. We found expansion of dendritic cells (DCs), CD14+ monocytes, and megakaryocytes progenitor cells (MP)/platelets and a reduction of naïve CD4+ T lymphocytes in patients with COVID-19, along with a significant decrease of CD8+ T lymphocytes, and natural killer cells (NKs) in patients in critical condition. The type I interferon (IFN-I), mitogen-activated protein kinase (MAPK), and ferroptosis pathways were activated while the disease was active, and recovered gradually after patient conditions improved. Consistent with this finding, the mRNA level of IFN-I signal-induced gene IFI27 was significantly increased in patients with COVID-19 compared with that of the controls in a validation cohort that included 38 patients and 35 controls. The concentration of interferon-α (IFN-α) in the serum of patients with COVID-19 increased significantly compared with that of the controls in an additional cohort of 215 patients with COVID-19 and 106 controls, further suggesting the important role of the IFN-I pathway in the immune response of COVID-19. TCR and BCR sequences analyses indicated that patients with COVID-19 developed specific immune responses against SARS-CoV-2 antigens. Our study reveals a dynamic landscape of human blood immune responses to SARS-CoV-2 infection, providing clues for therapeutic potentials in treating COVID-19.

Abstract Background As a novel high magnification module (HMM) combining with OCT (OCT-HMM) is able to detect the microstructure of retina, we apply it to explore the ultrastructure of the macula after closure of the idiopathic macular hole (IMH) by surgery. Methods This is an observational case series study in which patients with full-thickness IMHs who had undergone successful macular closure by vitrectomy and internal limiting membrane peeling and healthy subjects were recruited. After comprehensive ophthalmic examinations, the images of macular area were obtained and collected by professional operators using OCT-HMM. Then images were independently analyzed by 4 masked vitreoretinal specialists. Results A total of 24 IMH eyes and 42 healthy eyes were examined. HMM images were obtained in 10 IMH eyes. Among them, 4 eyes whose macula closed completely with recovery of photoreceptor layer presented a dark arc nasal to the fovea, oriented to the optic, and the notch of arc faced temporally. Six eyes in which the macula closed incompletely with photoreceptor cells loss revealed a dark ring with uneven bright spots inside. The other 14 eyes failed to obtain clear images by OCT-HMM. The contra lateral eyes of the patients and the healthy subjects’ eyes succeeded to obtain the HMM images which displayed evenly grey background thickly covered with tiny bright dots that was in similar size and evenly and widely distributed and there no dark arc or ring. OCT B-scan and IR images could be acquired in all of the IMH and healthy eyes. Conclusion The preliminary application of HMM has supplied us a brand-new insight into the microstructure of closed IMH. A dark arc sign could be detected with OCT-HMM in the macula which was functionally closed after surgery that was probably the healing mark on a microstructure photoreceptors level. Its existence and shape indicated that the functional closure followed by a retinal displacement mainly horizontally from temporal side to nasal side but not symmetric centripetally.

Fault induced delayed voltage recovery (FIDVR) is a credible concern in power systems with high penetration of single-phase air conditioner loads. Power system planning studies use dynamic load models, such as the Western Electricity Coordinating Council (WECC) composite load model CMPLDW to examine FIDVR in power systems. The behavior of modern variable frequency drive (VFD) air conditioners to voltage drops is not the same as traditional one- or two-speed air conditioning systems. This paper investigates the impact of increasing VFD air conditioner penetration within a power system on FIDVR events, by first modeling VFD air conditioners as a separate load and then as a power electronic component within the CMPLDW model. Simulation results show that increasing the penetration of VFD driven air conditioners decreases the post-fault voltage sag, recovery time, and number of customers interrupted by undervoltage load shedding.

This paper describes a novel method to synthesize load and feeder models, by estimating the load composition and the load parameters, using instantaneous voltage and current measurements, obtained at the distribution level, from disturbance events. A novel feeder model structure has been proposed in this work comprising of single-phase loads, three-phase loads, impedance loads, distribution transformers and distribution line segments. The load composition of the proposed feeder models and the motor load parameters are determined using a non-linear least squares algorithm integrated with an electromagnetic transient (EMT) analysis tool PSCAD. The efficacy of the proposed algorithm is examined for feeders at different physical locations and with distinctly varied load characteristics. Using this approach, parameters of the motor loads have been obtained within a fixed set of bounded values for each corresponding parameter. The ability of the proposed feeder and load models to capture severe fault induced delayed voltage recovery events (FIDVR) has also been discussed here.

Contact guidance for cell outgrowth refers to the phenomenon of the topography of the extracellular matrix regulating cell behaviors and functions. In tissue engineering, scaffolds with appropriate topographic cues for cell contact guidance show great potential in facilitating tissue repair and regeneration. Advanced 3D printing technology enables the fabrication of intricate and accurate structures for the study of the cellular responses and underlying mechanisms of contact guidance. This review focuses on 3D printing topographic cues for cell contact guidance. First, typical 3D printing technologies for manufacturing topographic cues are covered. Subsequently, cellular responses on 3D printing topographic cues in cell culture experiments are summarized. Then, the mechanisms of contact guidance on cell outgrowth are recapitulated. Finally, the major challenges and future perspectives for this field are discussed.

Nodal proteins provide crucial signals for mesoderm and endoderm induction. In zebrafish embryos, the nodal genes ndr1/squint and ndr2/cyclops are implicated in mesendoderm induction. It remains elusive how ndr1 and ndr2 expression is regulated spatiotemporally. Here we investigated regulation of ndr1 and ndr2 expression using Mhwa mutants that lack the maternal dorsal determinant Hwa with deficiency in β-catenin signaling, Meomesa mutants that lack maternal Eomesodermin A (Eomesa), Meomesa;Mhwa double mutants, and the Nodal signaling inhibitor SB431542. We show that ndr1 and ndr2 expression is completely abolished in Meomesa;Mhwa mutant embryos, indicating an essential role of maternal eomesa and hwa. Hwa-activated β-catenin signaling plays a major role in activation of ndr1 expression in the dorsal blastodermal margin, while eomesa is mostly responsible for ndr1 expression in the lateroventral margin and Nodal signaling contributes to ventral expansion of the ndr1 expression domain. However, ndr2 expression mainly depends on maternal eomesa with minor or negligible contribution of maternal hwa and Nodal autoregulation. These mechanisms may help understand regulation of Nodal expression in other species.

Gastric cancer, which has a high incidence and poor prognosis, remains a therapeutic challenge. Recently, neoadjuvant therapy has attracted increasing attention due to high recurrence rate and low survival rate after resection in most patients with advanced stage. Clinical trials show that neoadjuvant approaches confer a significant survival advantage for resectable locally advanced gastric cancer. The specific advantages of chemoradiotherapy compared with chemotherapy have not been clarified; optimal regimens and cycles, particularly in the preoperative setting, should be studied further; and trials aimed at determining the role of targeted and immunological therapies should be conducted.

Abstract Background To date, the fundamental pathophysiology underlying the occurrence and progression of psoriasis are still unanswered questions. Genome-wide association surveys have revealed that TNFAIP3 and TNIP1 were key biomarkers for psoriasis. Here, we intended to conduct a survey on the association between TNFAIP3 and TNIP1 gene polymorphisms and psoriasis risk. Methods A comprehensive search of four online databases—China National Knowledge Infrastructure (CNKI), PubMed, Embase, and Cochrane Library was undertaken up to August 25, 2019. We chose allele genetic model to deal with the original data. Newcastle–Ottawa scale (NOS) was used to evaluate the risk bias of each study. The RevMan 5.3 software was used to calculate the combined odds ratio and 95% confidence interval. Results In total, we included 13 case-control studies consist of 13,908 psoriasis patients and 20,051 controls in this work. Our results demonstrated that rs610604 in TNFAIP3 polymorphism was significantly associated with psoriasis risk using random-effect model (G vs. T, OR = 1.19, 95% CI: 1.09–1.31, P = 0.0002), and a significant association between rs17728338 in TNIP1 polymorphism and psoriasis vulnerability using fixed-effect model (A vs. G, OR = 1.69, 95% CI:1.58–1.80, P

Abstract Betulin (BE) has exceedingly become a potential natural product, providing multiple pharmacological and biological activities, including anti-cancer, anti-viral, and anti-inflammatory benefits. Previous research indicated that the solvatomorphism of BE can easily occur through crystallization with different organic solvents. This property of BE can directly affect its extraction, isolation, and preparation process. In this study, a system of thermogravimetry (TG)–differential thermal analysis (DTA) coupled with mass spectrometry (MS) with electron ionization (EI) and photoionization (PI) capability, equipped with the skimmer-type interface (i.e., skimmer-type interfaced TG–DTA–EI/PI–MS system), as a real-time and onsite analysis technique, was employed. Then, four solvatomorphs of BE, namely, with pyridine and water (A), sec-butanol (B), n,n-dimethylformamide (DMF) (C), and isopropanol (V), were analyzed for the first time. Finally, five kinds of the main volatile gaseous species, including H2O, pyridine, sec-butanol, DMF, and isopropanol, were identified clearly. Furthermore, the multi-step desolvation processes of the four solvatomorphs of BE were revealed by this system for the first time. This system showed great potential for the rapid and accurate analysis of various solvatomorphs of natural products. Graphic Abstract

An ongoing outbreak of severe respiratory pneumonia associated with the 2019 novel coronavirus has recently emerged in China. Here we report the epidemiological, clinical, laboratory and radiological characteristics of 19 suspect cases. We compared the positive ratio of 2019-nCoV nucleic acid amplification test results from different samples including oropharyngeal swab, blood, urine and stool with 3 different fluorescent RT-PCR kits. Nine out of the 19 patients had 2019-nCoV infection detected using oropharyngeal swab samples, and the virus nucleic acid was also detected in eight of these nine patients using stool samples. None of positive results was identified in the blood and urine samples. These three different kits got the same result for each sample and the positive ratio of nucleic acid detection for 2019-nCoV was only 47.4% in the suspect patients. Therefore, it is possible that infected patients have been missed by using nucleic acid detection only. It might be better to make a diagnosis combining the computed tomography scans and nucleic acid detection. Keywords: 2019 Novel coronavirus pneumonia, Clinical diagnosis, Nucleic acid amplification test

Immune checkpoint therapy targeting the PD-1/PD-L1 axis is a potentially novel development in anticancer therapy and has been applied to clinical medicine. However, there are still some problems, including a relatively low response rate, innate mechanisms of resistance against immune checkpoint blockades, and the absence of reliable biomarkers to predict responsiveness. In this study of in vitro and in vivo models, we demonstrate that PD-L1–vInt4, a splicing variant of PD-L1, plays a role as a decoy in anti–PD-L1 antibody treatment. First, we showed that PD-L1–vInt4 was detectable in clinical samples and that it was possible to visualize the secreting variants with IHC. By overexpressing the PD-L1–secreted splicing variant on MC38 cells, we observed that an immune-suppressing effect was not induced by their secretion alone. We then demonstrated that PD-L1–vInt4 secretion resisted anti–PD-L1 antibody treatment, compared with WT PD-L1, which was explicable by the PD-L1–vInt4’s decoying of the anti–PD-L1 antibody. The decoying function of PD-L1 splicing variants may be one of the reasons for cancers being resistant to anti–PD-L1 therapy. Measuring serum PD-L1 levels might be helpful in deciding the therapeutic strategy.

ObjectivesCOVID-19 and Non-Covid-19 (NC) Pneumonia encountered high CT imaging overlaps during pandemic. The study aims to evaluate the effectiveness of image-based quantitative CT features in discriminating COVID-19 from NC Pneumonia.Materials and methods145 patients with highly suspected COVID-19 were retrospectively enrolled from four centers in Sichuan Province during January 23 to March 23, 2020. 88 cases were confirmed as COVID-19, and 57 patients were NC. The dataset was randomly divided by 3:2 into training and testing sets. The quantitative CT radiomics features were extracted and screened sequentially by correlation analysis, Mann-Whitney U test, the least absolute shrinkage and selection operator (LASSO) logistic regression (LR) and backward stepwise LR with minimum AIC methods. The selected features were used to construct the LR model for differentiating COVID-19 from NC. Meanwhile, the differentiation performance of traditional quantitative CT features such as lesion volume ratio, ground glass opacity (GGO) or consolidation volume ratio were also considered and compared with Radiomics-based method. The receiver operating characteristic curve (ROC) analysis were conducted to evaluate the predicting performance.ResultsCompared with traditional CT quantitative features, radiomics features performed best with the highest Area Under Curve (AUC), sensitivity, specificity and accuracy in the training (0.994, 0.942, 1.0 and 0.965) and testing sets (0.977, 0.944, 0.870, 0.915) (Delong test, P < 0.001). Among CT volume-ratio based models using lesion or GGO component ratio, the model combining CT lesion score and component ratio performed better than others, with the AUC, sensitivity, specificity and accuracy of 0.84, 0.692, 0.853, 0.756 in the training set and 0.779, 0.667, 0.826, 0.729 in the testing set. The significant difference of the most selected wavelet transformed radiomics features between COVID-19 and NC might well reflect the CT signs.ConclusionsThe differentiation between COVID-19 and NC could be well improved by using radiomics features, compared with traditional CT quantitative values.