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Background: Vitamin D, as a common micronutrient, has been widely used in critically ill patients. However, whether supplementation of vitamin D in adult patients with sepsis can improve their prognosis remains controversial. Methods: Data from the Mart for Intensive Care IV database was used in this retrospective cohort study, and adult patients with sepsis were enrolled. Critically ill patients, admitted to intensive care units (ICUs) between 2008 and 2019 at the Beth Israel Deaconess Medical Center (BIDMC), were divided into the vitamin D supplementation group and non-vitamin D supplementation group. The primary outcomes were defined as all-cause in-hospital, 28-day, and 90-day mortality rates after admission to the ICU. A 1:1 propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and overlap weighting (OW) analyses were used to minimize selection bias and balance the baseline demographic characteristics. Regression and survival analyses were performed to assess the association between vitamin D supplementation and clinical outcomes in patients with sepsis. Results: In total, 3539 patients with sepsis were enrolled as study participants; of these, 315 were supplemented with vitamin D during their ICU stay. In-hospital, 28-day, and 90-day mortality rates were significantly lower in patients with sepsis supplemented with vitamin D. Multivariate regression analysis showed vitamin D supplementation as a potential protective factor for in-hospital mortality with an odds ratio (OR) = 0.70 (0.51–0.96) after adjusting for all confounders. The hazard ratios (HRs) for 28-day and 90-day mortality were 0.65 (0.50–0.85) and 0.70 (0.55–0.90), respectively. The survival analysis showed that the vitamin D supplementation group had a higher survival probability within 28 and 90 days (p-value < 0.05). These results remained relatively stable post PSM, IPTW, and OW. However, we found no evidence that vitamin D supplementation could shorten the length of stay in the ICU or hospital. Conclusions: Vitamin D supplementation during an ICU stay was associated with improved prognosis in patients with sepsis, as evidenced by lower in-hospital, 28-day, and 90-day mortality rates and lower disease severity-related scores, but showed no influence on the length of stay in the hospital or ICU.

Abstract Objectives The study aims to analyze the clinical characteristics of head and neck mucosal melanoma (MMHN) and the effects of multiple treatment modalities on distant metastasis, recurrence and survival rates to provide a reference for the individualized treatment of MMHN. Methods We retrospectively reviewed 262 patients with stage III–IVb MMHN treated from March 1986 to November 2018 at our cancer center. Results The median follow-up time was 34.0 months (range 1–262 months). The 5-year overall survival (OS), distant metastasis-free survival (DMFS) and disease-free survival (DFS) probabilities were 37.7%, 30.2%, and 20.3%, respectively. The 5-year OS rates for patients with stage III, stage IVA, and stage IVB MMHN were 67.0%, 24.1% and 8.3%, respectively (P

The evasive maneuver strategy for a fighter against a medium-range air-to-air missile is crucial to improving aircraft survivability.In this paper, the deep deterministic policy gradient algorithm to train the agent to learn the evasive maneuver strategy is studied.The missile-aircraft engagement model parameters are the input states.The aircraft control commands are taken as the output actions.The missile-aircraft pursuit-evasion model is taken as the learning environment.The shaping reward, including engagement model parameters and flight parameters, and the sparse reward of the engagement results are designed.Finally, the end-to-end evasive maneuver strategy from the state parameters to the aircraft control variables is realized.The attack zones of four classic evasive maneuvers based on prior knowledge by simulating are compared.It is proved that the evasion strategy developed in this paper is second only to the tail dive maneuver.However, this strategy has the lowest dependence on the specialized domain knowledge of missile evasion.

This paper proposes a nonlinear space dimension reduction method named Optimized Generative Topographic Mapping (OGTM). The Generative Topographic Mapping (GTM) method relies on the training sample set to capture the manifold of objective functions, and the generation of the training sample set causes an enormous computational burden. The choice of GTM hyperparameters has a significant influence on the design results. Traditional research has generally adopted the "cut-and-try" method to determine the corresponding hyperparameters and the best design, leading to wasted computational cost. The proposed OGTM overcomes this issue by minimizing the fitting error between the low-dimensional and high-dimensional samples, and the suitable hyperparameters are directly obtained by minimizing the fitting. In addition, the paper adopts a variable-fidelity sample filtration method to extract the promising regions with fewer sample points. To test and verify the effectiveness of the proposed method, it was then compared with the PCA and EGO methods in RAE2822 airfoil and ONERA M6 wing aerodynamic designs. The results demonstrate that the proposed method could capture the effective design space and generally take less computational cost to find the ideal results in all design optimizations. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to identify the hub gene in gastric cancer (GC) tumorigenesis. A biomarker prediction model was constructed and analyzed, and protein expression in histopathological samples was verified in a validation cohort.Methods: Differentially expressed genes (DEGs) were identified from GC projects in The Cancer Genome Atlas (TCGA) database. Functional enrichment analysis of DEGs was performed between the high- and low- Ribonuclease P protein subunit p30 (RPP30) expression groups. ROC analysis was performed to assess RPP30 expression to discriminate GC from normal tissues. Functional enrichment pathways and immune infiltration of DEGs were analyzed using GSEA and ssGSEA. Survival analysis and nomogram construction were performed to predict patient survival. Immunohistochemical staining of GC tissues was performed to validate RPP30 expression in GC and paracancerous samples.Results: Gene expression data and clinical information of 380 cases (375 GC samples and 32 para-cancerous tissues) were collected from TCGA database. The AUC for RPP30 expression was found to be 0.785. The G alpha S signaling pathway was the most significantly enriched signaling pathway. Primary therapy outcome (p < 0.001, HR = 0.243, 95% CI = 0.156–0.379), age (p = 0.012, HR = 1.748, 95% CI = 1.133–2.698), and RPP30 expression (p < 0.001, HR = 2.069, 95% CI = 1.346–3.181) were identified as independent prognostic factors. As a quantitative approach, a nomogram constructed based on RPP30 expression, age, and primary therapy outcome performed well in predicting patient survival. Nineteen of the 25 tissue samples from the validation cohort showed positive RPP30 expression in GC tissues, whereas 16 cases showed negative RPP30 staining in normal tissues. The difference between the two was statistically significant.Conclusion: High RPP30 expression was significantly correlated with disease progression and poor survival in GC, promoting tumorigenesis and angiogenesis via tRNA dysregulation. This study provides new and promising insights into the molecular pathogenesis of tRNA in GC.

Phosphatase and tensin homolog deleted on chromosome ten (PTEN) has been found to regulate longevity through the PI3K/Akt/FoxO pathway and maintenance of genome integrity in worms, flies, and mammals. However, limited information is available on the roles of PTEN in longevity of aquatic animals. Here we extended this paradigm using two closely related Argopecten scallops, Argopecten purpuratus, and Argopecten irradians, with significantly distinct life spans, which are commercially important bivalve species for fishery and aquaculture in China, United States, Peru, and Chile. The ORFs of the ApPTEN and AiPTEN were 1,476 and 1,473 bp, which encoded 491 and 490 amino acids, respectively. There were 48 synonymous and 16 non-synonymous SNPs and one InDel of three nucleotides between ApPTEN and AiPTEN, resulting in variations in 15 amino acids and lack of S453 in AiPTEN. Differences in conformation and posttranslational modification were predicted between ApPTEN and AiPTEN, which may indicate different activities of ApPTEN and AiPTEN. When the animals were subjected to nutrition restriction, the expression of both ApPTEN and AiPTEN was upregulated, with AiPTEN responded faster and more robust than ApPTEN. Ionizing radiation induced significantly elevated expression of ApPTNE but not AiPTEN in the adductor muscle, and the mortality rate of A. purpuratus was significantly lower than that of A. irradians, indicating that ApPTNE may play a protective role by maintaining the genome integrity. RNAi of ApPTNE significantly downregulated the expression of its downstream regulated genes known to favor longevity, such as FoxO, Mn-SOD, and CAT. These results indicated that PTEN may contribute to the longevity of A. purpuratus through regulation of nutrient availability and genomic stability, probably via PI3K/Akt/FoxO pathway. Our study may provide new evidence for understanding of the conservative functions of PTEN in regulation of lifespan in animals and human, and it may also benefit the selection of scallops strains with long lifespan and thus larger size.

BackgroundPatients with heart failure (HF) with diabetes may face a poorer prognosis and higher mortality than patients with either disease alone, especially for those in intensive care unit. So far, there is no precise mortality risk prediction indicator for this kind of patient.MethodTwo high-quality critically ill databases, the Medical Information Mart for Intensive Care IV (MIMIC-IV) database and the Telehealth Intensive Care Unit (eICU) Collaborative Research Database (eICU-CRD) Collaborative Research Database, were used for study participants’ screening as well as internal and external validation. Nine machine learning models were compared, and the best one was selected to define indicators associated with hospital mortality for patients with HF with diabetes. Existing attributes most related to hospital mortality were identified using a visualization method developed for machine learning, namely, Shapley Additive Explanations (SHAP) method. A new composite indicator ASL was established using logistics regression for patients with HF with diabetes based on major existing indicators. Then, the new index was compared with existing indicators to confirm its discrimination ability and clinical value using the receiver operating characteristic (ROC) curve, decision curve, and calibration curve.ResultsThe random forest model outperformed among nine models with the area under the ROC curve (AUC) = 0.92 after hyper-parameter optimization. By using this model, the top 20 attributes associated with hospital mortality in these patients were identified among all the attributes based on SHAP method. Acute Physiology Score (APS) III, Sepsis-related Organ Failure Assessment (SOFA), and Max lactate were selected as major attributes related to mortality risk, and a new composite indicator was developed by combining these three indicators, which was named as ASL. Both in the initial and external cohort, the new indicator, ASL, had greater risk discrimination ability with AUC higher than 0.80 in both low- and high-risk groups compared with existing attributes. The decision curve and calibration curve indicated that this indicator also had a respectable clinical value compared with APS III and SOFA. In addition, this indicator had a good risk stratification ability when the patients were divided into three risk levels.ConclusionA new composite indicator for predicting mortality risk in patients with HF with diabetes admitted to intensive care unit was developed on the basis of attributes identified by the random forest model. Compared with existing attributes such as APS III and SOFA, the new indicator had better discrimination ability and clinical value, which had potential value in reducing the mortality risk of these patients.

Abstract Lithium–sulfur batteries (Li‐S batteries) are promising next‐generation energy storage systems because of their high‐theoretical energy density. However, the commercialization of Li‐S batteries is still impeded by the aggregation of sulfur, low‐sulfur utilization, shuttling of dissolved polysulfides and sluggish reaction kinetics. Herein, we designed a hierarchically maple leaf‐like structured sulfur electrodes by in‐situ growth of ultrathin sulfur microcrystal on two‐dimensional MXene‐graphene‐cellulose nanofiber (MGN) matrice (denoted as IS‐MGN@S). The sulfur microcrystal as cathode can achieve improved kinetics than bulk sulfur due to its few layers of sulfur atoms, which is proved by the density functional theory calculations. The MXene not only confines polysulfides through strong chemisorption but also promotes the catalytic conversion of polysulfides. The introduction of graphene improves the conductivity and boosts the immobilization and conversion of polysulfides. As a result, the IS‐MGN@S cathode demonstrates remarkable electrochemical properties with a high‐initial capacity (1229 mAh g−1 at 0.2C), substantial improvement in rate capability (770 mAh g−1 at 2C), and stable long‐term cycling capacity. Moreover, the pouch cells with IS‐MGN@S cathode and gel electrolyte demonstrate excellent mechanical properties under mechanical damage (nail & cut tests, severe deformations), suggesting their promising applications for wearable electronic devices.

BackgroundNutrition is an essential factor in preventing and managing bronchopulmonary dysplasia (BPD), a multifactorial chronic respiratory disease in premature infants. This study examined the association between nutritional intakes during the first 2 weeks of life and BPD in extremely preterm infants.MethodsA retrospective single-center cohort study was performed in infants born

Abstract Objectives We aimed to understand the clinical characteristics and better predict the prognosis of patients with mucosal melanoma of the head and neck (MMHN) using a nomogram. Methods Three hundred patients with nometastatic MMHN were included. Multivariable Cox regression was performed to analyze independent prognostic factors for overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS), and these factors were used to develop a nomogram. Concordance indexes (C-indexes), calibration plots, and receiver operating characteristic (ROC) analysis were performed to test the predictive performance of the nomogram in both the primary (n = 300) and validation cohorts (n = 182). Results The primary tumor site, T stage and N stage were independent risk factors for survival and were included in the nomogram to predict the 3- and 5-year OS, DFS, DMFS, and LRRFS in the primary cohort. The C-indexes (both > 0.700), well-fit calibration plots, and area under the ROC curve (both > 0.700) indicated the high diagnostic accuracy of the nomogram, in both the primary and validation cohorts. The patients were divided into three groups (high-risk, intermediate-risk, and low-risk groups) according to their nomogram scores. The survival curves of OS, DFS, DMFS, and LRRFS were well separated by the risk groups in both cohorts (all P

Hepatocellular carcinoma (HCC) is one of the deadliest malignant tumors that are harmful to human health. Increasing evidence has underscored the critical role of the competitive endogenous RNA (ceRNA) regulatory networks among various human cancers. However, the complexity and behavior characteristics of the ceRNA network in HCC were still unclear. In this study, we aimed to clarify a phosphatase and tensin homolog (PTEN)-related ceRNA regulatory network and identify potential prognostic markers associated with HCC. The expression profiles of three RNAs (long non-coding RNAs [lncRNAs], microRNAs [miRNAs], and mRNAs) were extracted from The Cancer Genome Atlas (TCGA) database. The DLEU2L-hsa-miR-100-5p/ hsa-miR-99a-5p-TAOK1 ceRNA network related to the prognosis of HCC was obtained by performing bioinformatics analysis. Importantly, we identified the DLEU2L/TAOK1 axis in the ceRNA by using correlation analysis, and it appeared to become a clinical prognostic model by Cox regression analysis. Furthermore, methylation analyses suggested that the abnormal upregulation of the DLEU2L/TAOK1 axis likely resulted from hypomethylation, and immune infiltration analysis showed that the DLEU2L/TAOK1 axis may have an impact on the changes in the tumor immune microenvironment and the development of HCC. In summary, the current study constructing a ceRNA-based DLEU2L/TAOK1 axis might be a novel important prognostic factor associated with the diagnosis and prognosis of HCC.

Abstract Background Although the association between periventricular target collateral anastomosis and recurrent ipsilateral hemorrhage has been evaluated in adult patients with moyamoya disease (MMD), no studies have investigated the relationship between target anastomotic territory and recurrent ipsilateral hemorrhage. The goal of this study was to assess this association. Methods Consecutive adult MMD patients who had experienced initial intracranial hemorrhage and undergone conservative treatment were included. Two readers assessed angiographic results to identify the target anastomotic territory (medial medullary artery, lateral medullary artery, multiple medullary arteries, or nonmedullary artery) responsible for the hemorrhage. Cox proportional hazard regression models were used to estimate the risk of recurrent hemorrhage. Results In the 36 hemispheres with initial hemorrhage, the target anastomotic territory was in the anastomotic territory of the medial medullary artery in 10 (27.8%), lateral medullary artery in 15 (41.7%), multiple medullary arteries in 2 (5.6%), and a nonmedullary artery in 9 (25.0%) hemispheres. During 45.1 ± 40.0 months of follow-up, recurrent ipsilateral hemorrhage occurred in 44.4% (16/36) of hemispheres. The target anastomotic territories responsible for the recurrent event were in the anastomotic territory of the medial medullary artery in 9 (56.3%) hemispheres, lateral medullary artery in 6 (37.5%) hemispheres, and multiple medullary arteries in 1 (6.3%) hemisphere. The anastomotic territory of the medial medullary artery was associated with recurrent hemorrhage before (HR = 2.94; 95% CI, 1.07–8.08; p = 0.037) and after (HR = 6.65; 95% CI, 1.32–33.60; p = 0.022) adjustments were made for confounding factors. Conclusions The incidence of recurrent ipsilateral hemorrhage varies with the target anastomotic territory in adult patients with MMD. Medial target medullary artery anastomosis is a significant risk factor for recurrent ipsilateral hemorrhage.

Receptor Interacting Protein Kinase 3 (RIPK3) has a key role in TNF-induced necroptosis. Here, the authors combine solid state NMR measurements, MD simulations and cell based assays to characterize mouse RIPK3 and they present the structure of the RIPK3 amyloid core.

Abstract Insertion and Deletion (InDel) are common features in genomes and are associated with genetic variation. The whole-genome re-sequencing data from two parents (X1 and X2) of the elite cucumber (Cucumis sativus) hybrid variety Lvmei No.1 was used for genome-wide InDel polymorphisms analysis. Obtained sequence reads were mapped to the genome reference sequence of Chinese fresh market type inbred line ‘9930’ and gaps conforming to InDel were pinpointed. Further, the level of cross-parents polymorphism among five pairs of cucumber breeding parents and their corresponding hybrid varieties were used for evaluating hybrid seeds purity test efficiency of InDel markers. A panel of 48 cucumber breeding lines was utilized for PCR amplification versatility and phylogenetic analysis of these markers. In total, 10,470 candidate InDel markers were identified for X1 and X2. Among these, 385 markers with more than 30 nucleotide difference were arbitrary chosen. These markers were selected for experimental resolvability through electrophoresis on an Agarose gel. Two hundred and eleven (211) accounting for 54.81% of markers could be validated as single and clear polymorphic pattern while 174 (45.19%) showed unclear or monomorphic genetic bands between X1 and X2. Cross-parents polymorphism evaluation recorded 68 (32.23%) of these markers, which were designated as cross-parents transferable (CPT) InDel markers. Interestingly, the marker InDel114 presented experimental transferability between cucumber and melon. A panel of 48 cucumber breeding lines including parents of Lvmei No. 1 subjected to PCR amplification versatility using CPT InDel markers successfully clustered them into fruit and common cucumber varieties based on phylogenetic analysis. It is worth noting that 16 of these markers were predominately associated to enzymatic activities in cucumber. These agarose-based InDel markers could constitute a valuable resource for hybrid seeds purity testing, germplasm classification and marker-assisted breeding in cucumber.

Subnanocluster (SNC) cocatalysts are considered to be promising cocatalysts for photocatalytic hydrogen evolution reaction (HER) due to their rich surface-active sites and high atom utilization efficiency. Herein, a reductant-mediated in situ growth of the atomic clusters procedure is developed to synthesize SNC-Cu serving as advanced cocatalysts on TiO2 nanoparticles for HER. The optimized SNC-Cu/TiO2 catalyst, with 1.8 wt % metal mass loading, exhibits a remarkable hydrogen evolution rate of 6832 μmol g–1 h–1, which is ca. 25-fold that of bare TiO2 (273 μmol g–1 h–1 and comparable to that of 1 wt % Pt-modified TiO2 (7754 μmol g–1 h–1). Meanwhile, decent photostability and recyclability are also certified via a 20 h durability test. Comprehensive electron microscopy and spectroscopy characterizations unveil that the outstanding performance of SNC-Cu/TiO2 can be attributed to accelerated charge separation/transfer and suppressed photoinduced electron–hole recombination. Furthermore, in situ X-ray photoelectron spectroscopy and first-principle calculations reveal that the electron-localized SNC-Cu, with its abundant surface sites, facilitates *H adsorption and desorption, thus enhancing the HER activity significantly. This work highlights the promising potential of constructing noble-metal-free SNCs in semiconductors for photocatalytic HER. [ABSTRACT FROM AUTHOR]

The identification of novel age‐related biomarkers represents an area of intense research interest. Despite multiple studies associating DNA damage with aging, there is a glaring paucity of DNA damage‐based biomarkers of age, mainly due to the lack of precise methods for genome‐wide surveys of different types of DNA damage. Recently, we developed two techniques for genome‐wide mapping of the most prevalent types of DNA damage, single‐strand breaks and abasic sites, with nucleotide‐level resolution. Herein, we explored the potential of genomic patterns of DNA damage identified by these methods as a source of novel age‐related biomarkers using mice as a model system. Strikingly, we found that models based on genomic patterns of either DNA lesion could accurately predict age with higher precision than the commonly used transcriptome analysis. Interestingly, the informative patterns were limited to relatively few genes and the DNA damage levels were positively or negatively correlated with age. These findings show that previously unexplored high‐resolution genomic patterns of DNA damage contain useful information that can contribute significantly to both practical applications and basic science. [ABSTRACT FROM AUTHOR]

The oxidization of pure Li is rarely discussed, but substantially important in the design and optimization, especially the failure mechanism of Li metal anode for rechargeable batteries. In this context, the Li metal and inherent LiLi2O interface after oxidization are examined using first principles calculations. The results demonstrated that in Li itself, the Li ion exhibits a fluid-like transport feature, especially in the vacancy-assisted migration. The fresh Li surface can be oxidized quickly in air with a thick cover (mainly Li oxides), and an inherent LiLi2O interface is, therefore, introduced. With the lowest surface energy, the Li (111) plane is revealed with a strong capability of adsorbing O and N atoms to form the distorted XLi6 (X = O, N, etc.) octahedra in the outmost surface layers. Although the Li ion migrates fast in Li itself, the LiLi2O interface shows a sluggish Li diffusion kinetic in Li2O side. This ultimately leads to the Li diffusion prefers to go along the interface boundary in Li side, which loosens the LiLi2O interface structure to result in the exfoliation of surface metastable Li2O spontaneously during electrochemical cycles in Li-metal batteries.

Background: The goal of genetic breeding is to select variants with mutations that are related to expected traits, such as fast growth. Artificial induction has been widely used to obtain strains with more mutations for further selection. Ethylmethylsulfone (EMS) is one of the most commonly used chemical mutagens in plant and microorganism breeding. However, the application of EMS mutagenesis in shellfish has not been reported. The aim of this study is to evaluate the potential use of EMS as a mutagen in scallop breeding, especially in characterization of mutations in growth-related genes.Results: Our results indicated that hatching of about 50% of fertilized eggs was blocked by treatment with 20 mM EMS for 3 h and the resulted larvae developed normally into adult stages. We then evaluated the mutagenic effects of EMS by sequencing the genomes of 4 adult scallops from the control group and 12 from the treatment group at 8 months after fertilization. On average, after removing shared types of mutations, there were 1,151,380 ± 258,188 SNPs (Single Nucleotide Polymorphisms) and 229,256 ± 51,714 InDels (insertion-deletion) in each animal in the EMS treatment group, while there were only134841 ± 10,115 SNPs and 42,605 ± 5,136 InDels in the control group. The average mutation rate in the genome of the EMS treatment group (0.0137 ± 0.0013%) was about 9 times that of the control group (0.0015 ± 0.0002%). GO (Gene Ontology) annotation and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses revealed that mutations induced by EMS occurred evenly in most biological processes, cellular components and functions, as well in most pathways. However, significant lower percentage of mutations were found in the exonic region, in non-synonymous or Stopgain/Stoploss SNPs and in coding domains, suggesting apparent DNA repair or selection during grow-out stage. Analyses of the growth-related genes with mutations indicated that mutations in MFS (Major Facilitator Superfamily) and Tubulin were only found in the large-sized group (Five largest scallops: Treated-1, Treated-2, Treated-3, Treated-4, and Treated-5) and Homeobox and Socs (Suppressor of cytokine signaling) only in the small group (Two smallest scallops: Treated-11 and Treated-12). These results suggested that these genes may be involved in the regulation of growth in these animals, although further verification is certainly warranted.Conclusion: Treatment of fertilized eggs with 20 mM EMS for 3 h induced 9 times more mutations in scallop genomes. We found that mutations in MFS and Tubulin may be related to fast growth in the large-sized group and those mutations in Homeobox and SOCs may be involved in the slow growth in the small-sized scallops. EMS can be used to accelerate selection of economically important traits in molluscs.

Abstract The Li4Ti5O12 (LTO) spinel material, ranking at the second large market share after graphite, is a promising anode material for lithium‐ion batteries due to its good cycle stability, rate capability, and safety with both conventional and low‐temperature electrolytes. However, several critical challenges, such as the low capacity and gassing issue, hindered the wide applications of LTO anode. Recent progress indicated that the LTO performances are possible to be further improved by novel strategies, such as heterogeneous phase control, surface engineering, or overlithiation. To rethink and develop advanced LTO anodes, this review intensively associates the performances and modification strategies with the electronics/crystal structures. From a thermodynamic/kinetic point of view, we summarized the data obtained from recently developed characterization techniques, and the results of electrochemical performances and fundamental structures of LTO to potentially address several key challenges and issues toward advanced LTO anodes. As a result, light is shed on the future research direction of the LTO anodes.