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Abstract Untargeted metabolomic analysis using mass spectrometry provides comprehensive metabolic profiling, but its medical application faces challenges of complex data processing, high inter-batch variability, and unidentified metabolites. Here, we present DeepMSProfiler, an explainable deep-learning-based method, enabling end-to-end analysis on raw metabolic signals with output of high accuracy and reliability. Using cross-hospital 859 human serum samples from lung adenocarcinoma, benign lung nodules, and healthy individuals, DeepMSProfiler successfully differentiates the metabolomic profiles of different groups (AUC 0.99) and detects early-stage lung adenocarcinoma (accuracy 0.961). Model flow and ablation experiments demonstrate that DeepMSProfiler overcomes inter-hospital variability and effects of unknown metabolites signals. Our ensemble strategy removes background-category phenomena in multi-classification deep-learning models, and the novel interpretability enables direct access to disease-related metabolite-protein networks. Further applying to lipid metabolomic data unveils correlations of important metabolites and proteins. Overall, DeepMSProfiler offers a straightforward and reliable method for disease diagnosis and mechanism discovery, enhancing its broad applicability.

Abstract Methanogenic hydrocarbon degradation can be carried out by archaea that couple alkane oxidation directly to methanogenesis, or by syntrophic associations of bacteria with methanogenic archaea. However, metagenomic analyses of methanogenic environments have revealed other archaea with potential for alkane degradation but apparent inability to form methane, suggesting the existence of other modes of syntrophic hydrocarbon degradation. Here, we provide experimental evidence supporting the existence of a third mode of methanogenic degradation of hydrocarbons, mediated by syntrophic cooperation between archaeal partners. We collected sediment samples from a hot spring sediment in Tengchong, China, and enriched Hadarchaeota under methanogenic conditions at 60 °C, using hexadecane as substrate. We named the enriched archaeon Candidatus Melinoarchaeum fermentans DL9YTT1. We used 13C-substrate incubations, metagenomic, metatranscriptomic and metabolomic analyses to show that Ca. Melinoarchaeum uses alkyl-coenzyme M reductases (ACRs) to activate hexadecane via alkyl-CoM formation. Ca. Melinoarchaeum likely degrades alkanes to carbon dioxide, hydrogen and acetate, which can be used as substrates by hydrogenotrophic and acetoclastic methanogens such as Methanothermobacter and Methanothrix.

IntroductionEmerging evidence suggests that the vaginal microbiota is closely associated with cervical cancer. However, little is known about the relationships among the vaginal microbiota, vaginal metabolites, and cervical lesion progression in women undergoing cervical dysplasia.MethodsIn this study, to understand vaginal microbiota signatures and vaginal metabolite changes in women with cervical lesions of different grades and cancer, individuals with normal or cervical dysplasia were recruited and divided into healthy controls (HC) group, low-grade squamous intraepithelial lesions (LSIL) group, high-grade squamous intraepithelial lesions (HSIL) group, and cervical cancer (CC) group. Vaginal secretion samples were collected for 16S rRNA gene sequencing, liquid chromatography coupled with mass spectrometry (LC–MS)-based metabolomics, and integrated analysis.ResultsThe results demonstrated that bacterial richness and diversity were greater in the CC group than the other three groups. Additionally, Lactobacillus was found to be negatively associated with bacterial diversity and bacterial metabolic functions, which increased with the degree of cervical lesions and cancer. Metabolomic analysis revealed that distinct metabolites were enriched in these metabolite pathways, including tryptophan metabolism, retinol metabolism, glutathione metabolism, alanine, aspartate, and glutamate metabolism, as well as citrate cycle (TCA cycle). Correlation analysis revealed positive associations between CC group-decreased Lactobacillus abundance and CC group-decreased metabolites. Lactobacillus iners was both negative to nadB and kynU genes, the predicted abundance of which was significantly higher in the CC group. The linear regression model showed that the combination of the vaginal microbiota and vaginal metabolites has good diagnostic performance for cervical cancer.DiscussionOur results indicated a clear difference in the vaginal microbiota and vaginal metabolites of women with cervical dysplasia. Specifically altered bacteria and metabolites were closely associated with the degree of cervical lesions and cancer, indicating the potential of the vaginal microbiota and vaginal metabolites as modifiable factors and therapeutic targets for preventing cervical cancer.

Background: Transmembrane and tetratricopeptide repeat containing 1 (TMTC1) is a recently discovered enzyme involved in the O-mannosylation of cadherins and protocadherins. It has been implicated in various types of cancer, but the overall prognostic significance of TMTC1 in pan-cancer and its potential as an immunotherapeutic target remain unclear. Methods: We applied various bioinformatics methods to investigate the potential oncogenic roles of TMTC1 using public databases. This analysis involved examining the expression, prognosis, genetic alterations, immune infiltration, immunotherapy response, drug sensitivity, and regulatory mechanisms of the TMTC1 gene in diverse cancer types. Results: In this study, we observed that TMTC1 expression is reduced in 19 types of cancer (ACC, BLCA, BRCA, CESC, COAD, ESCA, GBM, KICH, KIRC, KIRP, LAML, LUAD, LUSC, PRAD, READ, STAD, THCA, UCEC, and UCS) compared to normal tissues. Conversely, TMTC1 expression is elevated in OV and PAAD relative to normal tissues. Moreover, our analysis revealed that high expression of TMTC1 was associated with worse overall survival (OS) outcomes in patients with ACC, BLCA, COAD, GBM, KIRP, OV, STAD, and UCEC, but better OS outcomes in patients with CESC, KIRC, LUSC, and PAAD. Notably, patients with TMTC1 mutations or deep deletions demonstrated longer OS, while those with TMTC1 amplification showed shorter OS. There was a significant correlation between the expression level of TMTC1 and the infiltration of cancer-associated fibroblasts (CAFs) and endothelial cells. Using data from six real-world immunotherapy cohorts of BLCA, SKCM and RCC, we discovered that high TMTC1 expression was associated with better OS or progression-free survival (PFS). Lastly, through TMTC1-related gene enrichment analysis, some biological processes and pathways were found to be significantly enriched, such as vascular endothelial growth factor receptor signaling pathway and ECM-receptor interaction. Conclusions: Our study demonstrates the prognostic significance of TMTC1 in pan-cancer and highlights its potential as an immunotherapeutic target.

Abstract Mutations in isocitrate dehydrogenases (IDH) are oncogenic events due to the generation of oncogenic metabolite 2-hydroxyglutarate. However, the role of wild-type IDH in cancer development remains elusive. Here we show that wild-type IDH2 is highly expressed in triple negative breast cancer (TNBC) cells and promotes their proliferation in vitro and tumor growth in vivo. Genetic silencing or pharmacological inhibition of wt-IDH2 causes a significant increase in α-ketoglutarate (α-KG), indicating a suppression of reductive tricarboxylic acid (TCA) cycle. The aberrant accumulation of α-KG due to IDH2 abrogation inhibits mitochondrial ATP synthesis and promotes HIF-1α degradation, leading to suppression of glycolysis. Such metabolic double-hit results in ATP depletion and suppression of tumor growth, and renders TNBC cells more sensitive to doxorubicin treatment. Our study reveals a metabolic property of TNBC cells with active utilization of glutamine via reductive TCA metabolism, and suggests that wild-type IDH2 plays an important role in this metabolic process and could be a potential therapeutic target for TNBC.

IntroductionEmerging evidence suggests that the gut microbiota is closely associated with bone homeostasis. However, little is known about the relationships among the bone mineral density (BMD) index, bone turnover markers, and the gut microbiota and its metabolites in postmenopausal women.MethodsIn this study, to understand gut microbiota signatures and serum metabolite changes in postmenopausal women with reduced BMD, postmenopausal individuals with normal or reduced BMD were recruited and divided into normal and OS groups. Feces and serum samples were collected for 16S rRNA gene sequencing, liquid chromatography coupled with mass spectrometry (LC-MS)-based metabolomics and integrated analysis.ResultsThe results demonstrated that bacterial richness and diversity were greater in the OS group than in the normal group. Additionally, distinguishing bacteria were found among the two groups and were closely associated with the BMD index and bone turnover markers. Metabolomic analysis revealed that the expression of serum metabolites, such as etiocholanolone, testosterone sulfate, and indole-3-pyruvic acid, and the corresponding signaling pathways, especially those involved in tryptophan metabolism, fatty acid degradation and steroid hormone biosynthesis, also changed significantly. Correlation analysis revealed positive associations between normal group-enriched Bacteroides abundance and normal group-enriched etiocholanolone and testosterone sulfate abundances; in particular, Bacteroides correlated positively with BMD. Importantly, the tryptophan-indole metabolism pathway was uniquely metabolized by the gut bacteria-derived tnaA gene, the predicted abundance of which was significantly greater in the normal group than in the control group, and the abundance of Bacteroides was strongly correlated with the tnaA gene.DiscussionOur results indicated a clear difference in the gut microbiota and serum metabolites of postmenopausal women. Specifically altered bacteria and derived metabolites were closely associated with the BMD index and bone turnover markers, indicating the potential of the gut microbiota and serum metabolites as modifiable factors and therapeutic targets for preventing osteoporosis.

To address the challenges of road extraction in high-resolution remote sensing images, this paper presents an enhanced UNet++ road extraction method that incorporates CBAM. The original UNet++ network is referenced, and the loss function is improved by introducing a new joint loss function. The enhanced UNet++ network utilizes an attention mechanism to enhance the network’s ability to identify road features, thereby improving the accuracy of road extraction. Additionally, a new joint loss function is employed to enhance the network’s stability and further improve its road extraction capability. Experimental validation is performed on the Massachusetts roads dataset and DeepGlobal road dataset. The experimental results demonstrate that this method outperforms U-Net, SegNet, and UNet++ networks in terms of IoU, Recall, OA, and Kappa. Specifically, on the Massachusetts road dataset, the OA and Kappa values are 94.92% and 0.9202, respectively. On the DeepGlobal road dataset, the OA and Kappa values for this algorithm are 98.12% and 0.9515, respectively. The ablation experiment confirms the effectiveness of the proposed enhancements. In conclusion, this paper presents a method that effectively extracts roads from high-resolution remote sensing images, exhibits a certain level of generalization ability, and can provide valuable support for road protection and planning.

Abstract Lymphoma is the sixth most common type of cancer worldwide. Under the current treatment standards, patients with lymphoma often fail to respond to treatment or relapse early and require further therapy. Hence, novel therapeutic strategies need to be explored and our understanding of the molecular underpinnings of lymphomas should be expanded. Ferroptosis, a non-apoptotic regulated cell death, is characterized by increased reactive oxygen species and lipid peroxidation due to metabolic dysfunction. Excessive or lack of ferroptosis has been implicated in tumor development. Current preclinical evidences suggest that ferroptosis participates in tumorigenesis, progression, and drug resistance of lymphoma, identifying a potential biomarker and an attractive molecular target. Our review summarizes the core mechanisms and regulatory networks of ferroptosis and discusses existing evidences of ferroptosis induction for the treatment of lymphoma, with intent to provide a framework for understanding the role of ferroptosis in lymphomagenesis and a new perspective of lymphoma treatment.

Abstract Lignin degradation is a major process in the global carbon cycle across both terrestrial and marine ecosystems. Bathyarchaeia, which are among the most abundant microorganisms in marine sediment, have been proposed to mediate anaerobic lignin degradation. However, the mechanism of bathyarchaeial lignin degradation remains unclear. Here, we report an enrichment culture of Bathyarchaeia, named Candidatus Baizosediminiarchaeum ligniniphilus DL1YTT001 (Ca. B. ligniniphilus), from coastal sediments that can grow with lignin as the sole organic carbon source under mesophilic anoxic conditions. Ca. B. ligniniphilus possesses and highly expresses novel methyltransferase 1 (MT1, mtgB) for transferring methoxyl groups from lignin monomers to cob(I)alamin. MtgBs have no homology with known microbial methyltransferases and are present only in bathyarchaeial lineages. Heterologous expression of the mtgB gene confirmed O‐demethylation activity. The mtgB genes were identified in metagenomic data sets from a wide range of coastal sediments, and they were highly expressed in coastal sediments from the East China Sea. These findings suggest that Bathyarchaeia, capable of O‐demethylation via their novel and specific methyltransferases, are ubiquitous in coastal sediments.

Abstract Background This study aims to explore the impacts of knowledge and attitude on the behavior of antibiotic use during the treatment of the common cold based on the expanding KAP model, and then identify the critical behavioral stage. Methods A cross-sectional study was conducted on 815 public from 21 community health centers (CHCs) in Chongqing, China. Based on the expanding KAP model, a self-administered questionnaire was designed to measure knowledge, attitude, multi-stage behavior, and perceived threat, in which multi-stage behavior was divided into pre-use antibiotic behavior, during-use antibiotic behavior, and post-use antibiotic behavior. A structural equation model was used to examine the model fit and the direct, indirect, mediating effects, and moderating effect of the variables. Results The expanding KAP showed good model fit indices with χ²/df = 0.537, RMSEA = 0.033, CFI = 0.973, GFI = 0.971, NFI = 0.934, TLI = 0.979. Knowledge had a positive effect on attitude (β = 0.503, p

Abstract Background Cervical cancer (CC) is a common gynecological malignancy with high morbidity worldwide. Butyrate, a short-chain fatty acid produced by intestinal flora, has been reported to inhibit cervical carcinogenesis. This study aimed to investigate the pro-apoptotic effects of butyrate on CC and the underlying mechanisms. Methods Human HeLa and Ca Ski cells were used in this study. Cell proliferation, cell migration and invasion were detected by CCK-8 and EdU staining, transwell and wound healing assay, respectively. Cell cycle, mitochondrial membrane potential and apoptosis were evaluated by flow cytometry. Western blot and RT-qPCR were carried out to examine the related genes and proteins to the mitochondrial complex Ι and apoptosis. Metabolite changes were analyzed by energy metabolomics and assay kits. The association between G protein-coupled receptor 41, 43, 109a and CC prognosis was analyzed using data from The Cancer Genome Atlas (TCGA). Results CCK-8 results showed significant inhibition of CC cell proliferation induced by butyrate treatment, which was confirmed by EdU staining and cell cycle detection. Data from the transwell and wound healing assay revealed that CC cell migration was dramatically reduced following butyrate treatment. Additionally, invasiveness was also decreased by butyrate. Western blot analysis showed that cleaved Caspase 3 and cleaved PARP, the enforcers of apoptosis, were increased by butyrate treatment. The results of Annexin V/PI staining and TUNEL also showed an increase in butyrate-induced apoptotic cells. Expression of Cytochrome C (Cytc), Caspase 9, Bax, but not Caspase 12 or 8, were up-regulated under butyrate exposure. Mechanistically, the decrease in mitochondrial NADH and NAD + levels after treatment with butyrate was observed by energy metabolomics and the NAD+/NADH Assay Kit, similar to the effects of the complex Ι inhibitor rotenone. Western blot results also demonstrated that the constituent proteins of mitochondrial complex Ι were reduced by butyrate. Furthermore, mitochondria-dependent apoptosis has been shown to be initiated by inhibition of the complex Ι. Conclusion Collectively, our results revealed that butyrate inhibited the proliferation, migration and invasion of CC cells, and induced mitochondrial-dependent apoptosis by inhibiting mitochondrial complex Ι.

IntroductionOur previous studies have demonstrated that tumor-infiltrating lymphocytes (TILs), including normal B cells, T cells, and natural killer (NK) cells, in diffuse large B-cell lymphoma (DLBCL) have a significantly favorable impact on the clinical outcomes of patients treated with standard chemoimmunotherapy. In this study, to gain a full overview of the tumor immune microenvironment (TIME), we assembled a flow cytometry cohort of 102 patients diagnosed with DLBCL at the Duke University Medical Center.MethodsWe collected diagnostic flow cytometry data, including the proportion of T cells, abnormal B cells, normal B cells, plasma cells, NK cells, monocytes, and granulocytes in fresh biopsy tissues at clinical presentation, and analyzed the correlations with patient survival and between different cell populations.ResultsWe found that low T cell percentages in all viable cells and low ratios of T cells to abnormal B cells correlated with significantly poorer survival, whereas higher percentages of normal B cells among total B cells (or high ratios of normal B cells to abnormal B cells) and high percentages of NK cells among all viable cells correlated with significantly better survival in patients with DLBCL. After excluding a small number of patients with low T cell percentages, the normal B cell percentage among all B cells, but not T cell percentage among all cells, continued to show a remarkable prognostic effect. Data showed significant positive correlations between T cells and normal B cells, and between granulocytes and monocytes. Furthermore, we constructed a prognostic model based on clinical and flow cytometry factors, which divided the DLBCL cohort into two equal groups with remarkable differences in patient survival and treatment response.SummaryTILs, including normal B cells, T cells, and NK cells, are associated with favorable clinical outcomes in DLBCL, and flow cytometry capable of quantifying the TIME may have additional clinical utility for prognostication.

Abstract Differential diagnosis of pulmonary nodules detected by computed tomography (CT) remains a challenge in clinical practice. Here, we characterize the global metabolomes of 480 serum samples including healthy controls, benign pulmonary nodules, and stage I lung adenocarcinoma. The adenocarcinoma demonstrates a distinct metabolomic signature, whereas benign nodules and healthy controls share major similarities in metabolomic profiles. A panel of 27 metabolites is identified in the discovery cohort (n = 306) to distinguish between benign and malignant nodules. The discriminant model achieves an AUC of 0.915 and 0.945 in the internal validation (n = 104) and external validation cohort (n = 111), respectively. Pathway analysis reveals elevation in glycolytic metabolites associated with decreased tryptophan in serum of lung adenocarcinoma vs benign nodules and healthy controls, and demonstrates that uptake of tryptophan promotes glycolysis in lung cancer cells. Our study highlights the value of the serum metabolite biomarkers in risk assessment of pulmonary nodules detected by CT screening.

Abstract Background A large proportion of prokaryotic microbes in marine sediments remains uncultured, hindering our understanding of their ecological functions and metabolic features. Recent environmental metagenomic studies suggested that many of these uncultured microbes contribute to the degradation of organic matter, accompanied by acetogenesis, but the supporting experimental evidence is limited. Results Estuarine sediments were incubated with different types of organic matters under anaerobic conditions, and the increase of uncultured bacterial populations was monitored. We found that (1) lignin stimulated the increase of uncultured bacteria within the class Dehalococcoidia. Their ability to metabolize lignin was further supported by the presence of genes associated with a nearly complete degradation pathway of phenolic monomers in the Dehalococcoidia metagenome-assembled genomes (MAGs). (2) The addition of cellulose stimulated the increase of bacteria in the phylum Ca. Fermentibacterota and family Fibrobacterales, a high copy number of genes encoding extracellular endoglucanase or/and 1,4-beta-cellobiosidase for cellulose decomposition and multiple sugar transporters were present in their MAGs. (3) Uncultured lineages in the order Bacteroidales and the family Leptospiraceae were enriched by the addition of casein and oleic acid, respectively, a high copy number of genes encoding extracellular peptidases, and the complete β-oxidation pathway were found in those MAGs of Bacteroidales and Leptospiraceae, respectively. (4) The growth of unclassified bacteria of the order Clostridiales was found after the addition of both casein and cellulose. Their MAGs contained multiple copies of genes for extracellular peptidases and endoglucanase. Additionally, 13C-labeled acetate was produced in the incubations when 13C-labeled dissolved inorganic carbon was provided. Conclusions Our results provide new insights into the roles of microorganisms during organic carbon degradation in anaerobic estuarine sediments and suggest that these macro and single molecular organic carbons support the persistence and increase of uncultivated bacteria. Acetogenesis is an additional important microbial process alongside organic carbon degradation. Video Abstract

Abstract Introduction The results of laboratory testing are crucial basis for clinicians to prescribe antimicrobial. Laboratory testing is a highly complex process, and increasing evidence suggests that errors and obstacles in the pre-analytical process (PP) will affect reasonable antimicrobial use. However, PP was an easily neglected link in hospital infection management and the current situation of it and the influencing factors of management are not clear. Methods A cross-sectional survey was conducted in the department of clinical, specimen collection, transportation, and inspection in 109 secondary and tertiary hospitals in Central China. The rate of antimicrobial susceptibility test request (AST) and related indexes of above departments were calculated to describe the situation. Management characteristics (frequency of training etc.) were described as proportions and fractional probit regression analysis was used to determine the influencing factors. Results The average rate of non restricted-use antimicrobial was 63%, the restricted-use was 86%, the special-use was 95%. The zero obstacle rate of specimen collection was 27.3%, of specimen transportation was 19.4% and of inspection feedback was 61.7%. There was a difference between the secondary and tertiary hospitals on non restricted-use (X2 = 22.968, P

BackgroundImproving the rural residents’ accessibility to and affordability of health care is recognized as a common target globally. The Health in All Policies approach, from the Declaration of Helsinki to the United Nations’ Decade Of Healthy Ageing, strengthened the far-reaching effect of large-scale public policies on health care–seeking behavior; however, the effects of national transport policy on health care–seeking behavior is unclear. ObjectiveThis quasi-experimental study aimed to examine the effects of the implementation of transport-driven poverty alleviation (TPA) policy on health care–seeking behavior and medical expenditure among older adults in rural areas and the mechanism underlying these effects. MethodsWe designed a quasi-experiment to estimate the effects of TPA policy implementation on health care–seeking behavior and medical expenditure among older adults in rural areas through a difference-in-differences (DID) analysis based on data from the China Health and Retirement Longitudinal Study in 2011, 2013, 2015, and 2018. The underlying mechanism was analyzed and effect modification patterns were further investigated by poor households, health status, and age. ResultsOur findings validated a positive contribution of TPA policy on health care–seeking behavior among older adults in rural areas. After the implementation of TPA policy, the number of inpatient visits increased by annually 0.35 times per person, outpatient medical expenditure increased by 192% per month, and inpatient medical expenditure increased by 57% annually compared with those of older adults in rural areas without the implementation of TPA policy. Further, there was a significant modification effect, with a positive effect among poor households, healthier older adults, and those aged 60-80 years. Additionally, the policy improved the patients’ capabilities to seek long-distance care (β=23.16, 95% CI –0.99 to 45.31) and high-level hospitals (β=.08, 95% CI –0.02 to 0.13), and increased individual income to acquire more medical services (β=4.57, 95% CI –4.46 to 4.68). ConclusionsThese findings validate the positive contribution of TPA policy on health care–seeking behavior among older adults in rural areas; however, the medical expenditure incurred was also high. Concerted efforts are needed to address health care–seeking dilemmas in rural areas, and attention must be paid to curbing medical expenditure growth for older adults in rural areas during TPA policy implementation.

This paper investigates how Chinese taxi drivers utilize low-tech equipment, such as handheld radios and mobile phone services, to form local ride-hailing networks. Previous studies have analyzed how Internet platforms like Didi Chuxing have reshaped labor relations through technology and policies, but they have ignored the fact that outside metropolitan areas, traditional technological solutions, such as on-call radio platforms, have not been replaced by the rapidly expanding ride-hailing platforms. Therefore, to outline China’s diverse ICT practice environment, this paper focuses on a case study in two Chinese towns (Laizhou, Shandong; Ziyang, Sichuan), shifting the attention from metropolitan areas to neglected fourth- and fifth-tier cities. After reviewing the previous advancements in mobile communication technology, we discuss the economic, cultural, and social motivations behind the use of ‘low-tech’ devices and cooperative services by the Chinese taxi drivers in question.

Abstract Background The states of IPC (Infection Prevention and Control) is serious under the COVID-19 pandemic. Nosocomial infection reporting is of great significance to transparent management of IPC in regard to the COVID-19 pandemic. We aimed to explore the relationship between communication openness and nosocomial infection reporting, explore the mediating effect of team cohesion in the two, and provide evidence-based organizational perspective for improving IPC management in the hospitals. Method A questionnaire was used to collect data on communication openness, team cohesion and nosocomial infection reporting in 3512 medical staff from 239 hospitals in Hubei, China. Structural Equation Model (SEM) was conducted to examine the hypothetical model. Result Communication openness was positively related to nosocomial infection reporting (β = 0.540, p

BackgroundChronic pain, sleep disorders, and depression are major global health concerns. Recent studies have revealed a strong link between sleep disorders and pain, and each of them is bidirectionally correlated with depressive symptoms, suggesting a complex relationship between these conditions. Social participation has been identified as a potential moderator in this complex relationship, with implications for treatment. However, the complex interplay among sleep disorders, pain, depressive symptoms, and social participation in middle- and old-aged Asians remains unclear. ObjectiveThis study aimed to examine the bidirectional relationship between sleep disorders and pain in middle- and old-aged Chinese and measure the role of depression as a mediator and social participation as a moderator in this bidirectional relationship through a dynamic cohort study. MethodsWe used data from the China Health and Retirement Longitudinal Study across 5 years and included a total of 7998 middle- and old-aged people (≥45 years old) with complete data in 2011 (T1), 2015 (T2), and 2018 (T3). The cross-lag model was used to assess the interplay among sleep disorders, pain, depressive symptoms, and social participation. Depressive symptoms were assessed by the 10-item Centre for Epidemiological Studies Depression scale. Sleep disorders were assessed by a single-item sleep quality scale and nighttime sleep duration. The pain score was the sum of all pain locations reported. Social participation was measured using self-reported activity. ResultsOur results showed significant cross-lagged effects of previous sleep disorders on subsequent pain at T2 (β=.141; P

BackgroundHealthcare-associated infections have become a serious public health problem. Various types of information systems have begun to be applied in hospital infection prevention and control (IPC) practice. Clinicians are the key users of these systems, but few studies have assessed the use of infection prevention and control information systems (IPCISs) from their perspective. ObjectiveThis study aimed to (1) apply the extended DeLone and McLean Information Systems Success model (D&M model) that incorporates IPC culture to examine how technical factors like information quality, system quality, and service quality, as well as organizational culture factors affect clinicians’ use intention, satisfaction, and perceived net benefits, and (2) identify which factors are the most important for clinicians’ use intention. MethodsA total of 12,317 clinicians from secondary and tertiary hospitals were surveyed online. Data were analyzed using partial least squares-structural equation modeling and the importance-performance matrix analysis. ResultsAmong the technical factors, system quality (β=.089-.252; P

PurposeAutologous chimeric antigen receptor (CAR) T cell therapy is one of the most significant breakthroughs in hematological malignancies. However, a three-week manufacturing cycle and ineffective T cell dysfunction in some patients hinder the widespread application of auto-CAR T cell therapy. Studies suggest that cord blood (CB), with its unique biological properties, could be an optimal source for CAR T cells, providing a product with ‘off-the-shelf’ availability. Therefore, exploring the potential of CB as an immunotherapeutic agent is essential for understanding and promoting the further use of CAR T cell therapy.Experimental designWe used CB to generate CB-derived CD19-targeting CAR T (CB CD19-CAR T) cells. We assessed the anti-tumor capacity of CB CD19-CAR T cells to kill diffuse large B cell lymphoma (DLBCL) in vitro and in vivo.ResultsCB CD19-CAR T cells showed the target-specific killing of CD19+ T cell lymphoma cell line BV173 and CD19+ DLBCL cell line SUDHL-4, activated various effector functions, and inhibited tumor progression in a mouse (BALB/c nude) model. However, some exhaustion-associated genes were involved in off-tumor cytotoxicity towards activated lymphocytes. Gene expression profiles confirmed increased chemokines/chemokine receptors and exhaustion genes in CB CD19-CAR T cells upon tumor stimulation compared to CB T cells. They indicated inherent changes in the associated signaling pathways in the constructed CB CAR T cells and targeted tumor processes.ConclusionCB CD19-CAR T cells represent a promising therapeutic strategy for treating DLBCL. The unique biological properties and high availability of CB CD19-CAR T cells make this approach feasible.

Background At present, pre-eclampsia is a growing concern and still a diagnostic challenge for obstetricians. Aims This study aimed to evaluate whether the relationship of second trimester of pregnancy neutrophil count differed among pregnancies with mild preeclampsia, severe preeclampsia, and healthy status and explore whether or not neutrophil count in the second trimester of pregnancy would be useful as new predictors of subsequent preeclampsia. Patients and methods This study involved 933 pregnancies from 1 January 2018 to 30 January 2021, comprising 396 healthy pregnancies, 222 pregnancies with mild preeclampsia, and 315 pregnancies with severe preeclampsia. The relationship between preeclampsia and neutrophil count was analyzed by multiple logistic regression. In addition, maternal placental tissues of three groups were immunohistochemically stained for myeloperoxidase (MPO). Results Neutrophil count was significantly higher in pregnancies with preeclampsia (including pregnancies with mild and severe preeclampsia) than that in healthy pregnancies. The neutrophil count level was prominently higher in patients with severe preeclampsia compared with those with mild preeclampsia (p

WEE1 has emerged as an attractive target in epithelial ovarian cancer (EOC), but how EOC cells may alter their sensitivity to WEE1 inhibition remains unclear. Here, through a cell cycle machinery–related gene RNAi screen, we found that targeting outer dense fiber of sperm tails 2–like (ODF2L) was a synthetic lethal partner with WEE1 kinase inhibition in EOC cells. Knockdown of ODF2L robustly sensitized cells to treatment with the WEE1 inhibitor AZD1775 in EOC cell lines in vitro as well as in xenografts in vivo. Mechanistically, the increased sensitivity to WEE1 inhibition upon ODF2L loss was accompanied by accumulated DNA damage. ODF2L licensed the recruitment of PKMYT1, a functionally redundant kinase of WEE1, to the CDK1–cyclin B complex and thus restricted the activity of CDK1 when WEE1 was inhibited. Clinically, upregulation of ODF2L correlated with CDK1 activity, DNA damage levels, and sensitivity to WEE1 inhibition in patient-derived EOC cells. Moreover, ODF2L levels predicted the response to WEE1 inhibition in an EOC patient–derived xenograft model. Combination treatment with tumor-targeted lipid nanoparticles that packaged ODF2L siRNA and AZD1775 led to the synergistic attenuation of tumor growth in the ID8 ovarian cancer syngeneic mouse model. These data suggest that WEE1 inhibition is a promising precision therapeutic strategy for EOC cells expressing low levels of ODF2L.

The combined quasineutral and zero-viscosity limits of the bipolar Navier-Stokes-Poisson system with boundary are rigorously proved by establishing the nonlinear stability of the approximate solutions. Based on the conormal energy estimates, we showed that the solutions for the original system converge strongly in H3 space towards the solutions of the one-fluid compressible Euler system as long as the amplitude of the boundary layers is small enough.

Hand hygiene behavior (HHB) in healthcare settings remains suboptimal globally. Self-expectation leadership and organizational commitment are emphasized as important factors influencing HHB. However, there are no studies to support any relationship between self-expectation leadership and organizational commitment to HHB. This study will fill the gap by applying implicit leadership theory (ILT) to support the further promote HHB among medical staff. A cross-sectional study of 23,426 medical staff was conducted in all second-level and third-level hospitals in Hubei province, China. Based on ILT, an online self-administered and anonymous questionnaire was designed for measuring the medical staff’s self-expectation leadership, organizational commitment, and HHB based on Offermann’s 8 dimensions scale, Chang’s 3 dimensions scale, and the specification of hand hygiene for healthcare workers, respectively, in which self-expectation leadership was divided into positive traits and negative traits parts. The structural equation model was used to examine the direct, indirect, and mediating effects of the variables. Positive traits of self-expectation leadership had a positive effect on organizational commitment (β = 0.617, p < 0.001) and HHB (β = 0.180, p < 0.001). Negative traits of self-expectation leadership had a negative effect on organizational commitment (β = –0.032, p < 0.001), while a positive effect on HHB (β = 0.048, p < 0.001). The organizational commitment had a positive effect on HHB (β = 0.419, p < 0.001). The mediating effect of the organizational commitment showed positively between positive traits of self-expectation leadership and HHB (β = 0.259, p < 0.001), while negatively between negative traits of self-expectation leadership and HHB (β = –0.013, p < 0.001). Positive traits of self-expectation leadership are important predictors of promoting organizational commitment and HHB, while negative traits of self-expectation leadership have a limited impact on organizational commitment and HHB in the field of healthcare-associated infection prevention and control. These findings suggest the need to focus on positive traits of self-expectation leadership; although negative traits of self-expectation leadership can also promote HHB to a lesser degree among medical staff, it will reduce their organizational commitment.

Abstract Wireless communication refers to long-distance transmission communication between multiple nodes without propagation through conductors or cables, and wireless communication can be carried out by radio and electromagnetic waves, etc. Judging from the current situation, the home space positioning design of the medical and elderly care communities is not perfect, which affects the traditional home care. Wireless communication can give wisdom, coordination, and development space in the smart elderly care space positioning design, allowing the elderly to interact, contact, and know their precise location and behavior. This article mainly studies the design and implementation of smart pension space positioning under BIM technology. This paper introduces the frontier of Internet-of-things technology and the theory of sensor network topology control. It uses basic IoT technology to implement the "point, line, and surface" combination of personnel placement algorithms, sensor network communication protocols, topology checks, security models, sensor network wireless communication units, and wireless communication technology. The basic technology and communication technology of personnel deployment based on BIM technology are introduced, the development strategy of wireless communications node is studied, the installation of equipment radio personnel and communication equipment is designed, and the system management platform for the design and development of staff placement in pension institutions is provided. The Web site's information service management, standardized procedures, optimized services, provision of information, intelligent management, and pension services. The experimental results of this paper show that the smart pension space positioning under the BIM technology solves the management loopholes in nursing homes, shortage of nursing staff, inefficiency, lack of services, and family conflicts. It improves the efficiency of the elderly by 25% and the safety index by 23–27%. The development of wireless communication technology promotes the development of intelligent pension space. It will be an important future development direction for the smart community pension.

Abstract Gordonia sp. are members of the actinomycete family, their contribution to the environment improvement and environmental protection by their biological degradation ability, but there are few studies on the antimicrobial activity of their secondary metabolites. Our team isolated and purified an actinomycete WA 4-31 from the intestinal tract of Periplaneta americana, firstly identified the strain WA 4-31 by the morphological characteristics and the phylogenetic analyses, and found it was completely homologous to the strain of Gordonia terrae from the Indian desert. Meanwhile, actinomycin D (1), actinomycin X2 (2), mojavensin A (3) and cyclic (leucine-leucne) dipeptide (4) were obtained from the EtOAc extract from the broth of WA 4-31. Compounds 1–4 showed anti-fungus activities against Candida albicans, Aspergillus niger, A. fumigatus and Trichophyton rubrum, also anti-MRSA and inhibited Escherichia coli in different degree. Interestingly, we found when 3 was mixed with 4 with ratio of 1:1, the activity of the mixture on anti-Candida albicans was better than the single. Besides, compounds 1–3 had varying degrees of antiproliferative activities on CNE-2 and HepG-2 cell lines. These indicated that Gordonia rare actinomycete from the intestinal tract of Periplaneta americana possessed a potential as a source of active secondary metabolites.

Sensation (the reflection of past experience in the mind) is the reflection of the brain on the individual attributes of objective things that directly act on the sense organs. Feeling is the most elementary cognitive process and the simplest psychological phenomenon. Vision is a kind of sense, and sense is produced by objective things acting on the sense organs. But at present, it is rare to analyze interior design exhibition from the perspective of visual psychology, an emerging science, as an interdisciplinary attempt, only in interior design research. Therefore, the study of sensory process should start from its external stimuli, in order to first understand how it acts on the sensory organs to produce sensory phenomena. This paper mainly studies the visual performance of psychological factors in interior design under the background of artificial intelligence. This paper proposes a K-means clustering algorithm and a localization algorithm fused with visual and inertial navigation. The distance thresholds corresponding to the SIFT feature descriptors of threshold T1, 128D, 96D, 64D, and 32D are 170, 160, 150, and 90, respectively. This verifies that the candidate image with the highest number of matching points is considered the best matching image.

B‐cell non‐Hodgkin's lymphoma (NHL) is a class of heterogeneous diseases with variable clinical outcomes. Immunosuppression is particularly common in the subtypes of lymphoma with poor prognosis, but the underlying mechanism remains unclear. Using a RT‐PCR array analysis, we have identified that glycosyltransferase 1 domain‐containing 1 (GLT1D1), an enzyme that transfers glycosyl groups to proteins, is highly upregulated in the incurable subtype of B‐cell NHL and in early relapse diffuse large B‐cell lymphoma. Analysis of clinical specimens revealed that GLT1D1 expression was positively correlated with the level of glycosylated programmed cell death‐ligand 1 (PD‐L1) in B‐cell NHL and that high GLT1D1 expression was associated with poor prognosis. Mechanistically, we showed that GLT1D1 transferred N‐linked glycans to PD‐L1, thus promoting the immunosuppressive function of glycosylated PD‐L1. Downregulation of GLT1D1 resulted in a decrease of glycosylated PD‐L1 and enhanced cytotoxic T‐cell function against lymphoma cells. In vivo, overexpression of GLT1D1 promoted tumor growth by facilitating tumor immune escape through increased levels of PD‐L1. Our work has identified GLT1D1 as a predictive biomarker for B‐cell NHL. It has also shown that this enzyme enhances PD‐L1 stabilization via N‐glycosylation, thus promoting immunosuppression and tumor growth. As such, GLT1D1 might be a novel therapeutic target for the treatment of B‐NHL.

Abstract Background Obesity is a severe public health threat worldwide. Emerging evidence suggests that gut microbiota dysbiosis is closely associated with obesity and its related metabolic complications. The aim of the present study is to investigate the effects of polysaccharide extracted from WuGuChong (PEW) on high-fat diet (HFD)-induced obesity, and the potential mechanisms involving modulation of the gut microbiota composition. Methods Mice were fed a normal chow diet and a high-fat diet with or without PEW (300 mg/kg/day) by oral gavage for 8 weeks. Body weight, obesity-related metabolic disorders, and gut microbiota were examined at the end of the experiment. Results PEW supplementation reduces body weight, adipose hypertrophy, liver steatosis, insulin resistance and systemic inflammation in HFD-fed mice, as well as maintains intestinal epithelium integrity. High-throughput 16S rRNA analysis demonstrates that PEW supplementation alters the composition of gut microbiota. The Firmicutes to Bacteroidetes ratio and the relative abundance of Proteobacteria are increased in HFD-fed mice, which are reversed by PEW supplementation to approximately the control levels. Conclusions Our results suggest that PEW may be used as a bioactive ingredient to prevent obesity and its related metabolic disorders by modulating the composition of gut microbiota.

Outlier detection over sliding window is a fundamental problem in the domain of streaming data management, which has has been studied over 10 years. The key to supporting outlier detection is to construct a neighbour list for each object, which is used for predicting which objects may become outliers or are impossible to become outliers. However, existing work ignores the fact that, outliers amount is usually small, in which it is unnecessary to construct neighbour-list for all objects when they arrive in the window. It causes both high space and computational cost, which turns the solution infeasible for working under edge computation environment. In this paper, we propose a novel framework named PTAOD (Probabilistic Threshold-based Approximate Outlier Detection). Firstly, we propose an algorithm for evaluating the probability of a newly arrived object becoming an outlier before it expires from the window, using evaluating result for avoiding unnecessary candidate maintenance. In addition, we introduce a novel index namely ZHB-Tree (Z-order-based Hash B-Tree) to maintain streaming data. Last of all, we propose a novel algorithm to maintain candidate outliers. Theoretical analysis and extensive experimental results demonstrate the effectiveness of the proposed algorithms.

The overuse of antibiotics remains serious and has led to a dramatic increase in antimicrobial resistance, which poses a significant threat to global public health, although much action has been taken by World Health Organization and countries. As the direct evidence to guide the prescribing of antibiotics, the Antimicrobial Susceptibility Testing (AST) results were biased by sample errors, which was urgent and poorly explored in quality management. This study aimed to analyze sample errors pre-AST and its influencing factors from the perspective of hospital management, to provide evidence for promoting rational antibiotic use and antimicrobial stewardship. A cross-sectional survey of 5963 clinical nurses involved in pathogenic sample collection was conducted in 118 public hospitals in Hubei province, China. Dependent variables were sample errors attributed to resources and technology-oriented, capability-oriented, and attitude-oriented errors, which were measured by times per week. Independent variables were sample management information such as guidelines, record after collection, performance appraisal, training, and publicity activities, in which guidelines, record time, and record method were dummy variables, with 1 indicating having and 0 not. Others were continuous variables ranging from 0 to 4 times per month. Ordinary Least Square regression models were performed to analyze influencing factors on sample error times. The averages of sample errors on resource and technology-oriented, capability-oriented, and attitude-oriented were 1.48, 1.35, and 1.36 times per week, and their proportion were 25.3%, 38.9%, and 35.8%, respectively. The results showed that recording timeliness (r = −0.354, p < 0.01), record using both paper and digital methods(r = −0.060, p < 0.01), performance appraisal(r = −0.188, p < 0.01), and publicity activities (r = −0.186, p < 0.01) significantly reduced times of resource and technology-oriented errors. Performance appraisals(r = −0.171, p < 0.01) and training activities (r = −0.208, p < 0.01) had a positive impact on the reduction of capability-oriented error times. The times of attitude-oriented error decreased significantly when recording timeliness (r = −0.299, p < 0.01), implementing performance appraisal (r = −0.164, p < 0.01), and training activities (r = −0.188, p < 0.01). This study found that there was a high frequency of sample errors in quality management, especially capability-oriented and attitude-oriented errors. Sample information management, performance appraisal, training, and publicity activities were associated with the quality of samples valuable for the rational use of antibiotics.

Methanogens can produce methane in anaerobic environments via the methanogenesis pathway, and are regarded as one of the most ancient life forms on Earth. They are ubiquitously distributed across distinct ecosystems and are considered to have a thermophilic origin. In this study, we isolated, pure cultured, and completely sequenced a single methanogen strain DL9LZB001, from a hot spring at Tengchong in Southwest China. DL9LZB001 is a thermophilic and hydrogenotrophic methanogen with an optimum growth temperature of 65 °C. It is a putative novel species, which has been named Methanothermobacter tengchongensis—a Class I methanogen belonging to the class Methanobacteria. Comparative genomic and ancestral analyses indicate that the class Methanobacteria originated in a hyperthermal environment and then evolved to adapt to ambient temperatures. This study extends the understanding of methanogens living in geothermal niches, as well as the origin and evolutionary history of these organisms in ecosystems with different temperatures.

Energy intensity measured by energy consumption per unit of GDP has always been the main assessment indicator for the design of energy-saving policies, but its accuracy is highly dependent on the reliability of GDP data. This paper finds that the indicator accuracy is improving after the central government has included energy intensity into the performance appraisal system for local officials. This means that the energy-saving target-based performance evaluation has restrained the data misrepresentation behavior of local officials. Further mechanism analysis shows that the pressure of energy saving restricts the development of the industrial sector, which weakens the ability of local governments to manipulate GDP data, thus improving the accuracy of energy intensity statistics. These findings provide some insightful references for China’s future green development and policy design.

Abstract Background Internal tandem duplications (ITD) within the juxtamembrane domain of FMS-like tyrosine kinase 3 (FLT3) represent a poor prognostic indicator in acute myeloid leukemia (AML). Therapeutic benefits of tyrosine kinase inhibitors, such as sorafenib, are limited due to the emergence of drug resistance. While investigations have been conducted to improve the understanding of the molecular mechanisms underlying the resistance to this FLT3 inhibitor, a profile of cell functioning at the metabolite level and crosstalk between metabolic pathways has yet to be created. This study aimed to elucidate the alteration of metabolomic profile of leukemia cells resistant to the FLT3 inhibitor. Methods We established two sorafenib-resistant cell lines carrying FLT3/ITD mutations, namely the murine BaF3/ITD-R and the human MV4-11-R cell lines. We performed a global untargeted metabolomics and stable isotope-labeling mass spectrometry analysis to identify the metabolic alterations relevant to the therapeutic resistance. Results The resistant cells displayed fundamentally rewired metabolic profiles, characterized by a higher demand for glucose, accompanied by a reduction in glucose flux into the pentose phosphate pathway (PPP); and by an increase in oxidative stress, accompanied by an enhanced glutathione synthesis. We demonstrated that the highest scoring network of altered metabolites in resistant cells was related to nucleotide degradation. A stable isotope tracing experiment was performed and the results indicated a decrease in the quantity of glucose entering the PPP in resistant cells. Further experiment suggested that the inhibition of major enzymes in the PPP consist of glucose-6-phosphate dehydrogenase deficiency (G6PD) in the oxidative arm and transketolase (TKT) in the non-oxidative arm. In addition, we observed that chronic treatment with sorafenib resulted in an increased oxidative stress in FLT3/ITD-positive leukemia cells, which was accompanied by decreased cell proliferation and an enhanced antioxidant response. Conclusions Our data regarding comparative metabolomics characterized a distinct metabolic and redox adaptation that may contribute to sorafenib resistance in FLT3/ITD-mutated leukemia cells.

Piezoelectric materials, especially Pb-based piezoelectric materials, are widely used in the key components of sensors, actuators, and transducers. Due to the rising concern of the toxicity of Pb, global legislation has been adopted to restrict the use of Pb. Given that the available Pb-free piezoelectric materials cannot replace the Pb-based ones for various reasons, we designed and fabricated a low-Pb piezoelectric solid-solution ceramic system, (1–x)Ba(Zr0.18Ti0.82)O3–x(Ba0.78Pb0.22)TiO3 (denoted as BZ0.18T–xBP0.22T herein). The crystal structure, ferroelectric, dielectric, and piezoelectric properties of the BZ0.18T–xBP0.22T system were systematically studied. With the increase in BP0.22T content, the structure of the samples changed from a rhombohedral phase to a tetragonal phase; the intermediate composition x = 0.5 was located at the morphotropic phase boundary of the system and corresponded to the state with the coexistence of the rhombohedral and tetragonal phases. Moreover, x = 0.5 exhibited the optimum comprehensive properties among all the samples, with a piezoelectric coefficient d33 of 240 pC/N, a maximum dielectric temperature Tm of 121.1°C, and a maximum polarization Pm of 15 μC/cm2. Our work verifies the validity of the route to design low-Pb high-piezoelectric materials and may stimulate the interests for exploring new low-Pb high-performance ferroelectric and piezoelectric materials.

The microphysical parameters of snowfall directly impact hydrological and atmospheric models. During the International Collaborative Experiment hosted at the Pyeongchang 2018 Olympic and Paralympic Winter Games (ICE-POP 2018), dual-frequency radar retrievals of particle size distribution (PSD) parameters were produced and assessed over complex terrain. The NASA Dual-frequency Dual-polarized Doppler Radar (D3R) and a collection of second-generation Particle Size and Velocity (PARSIVEL2) disdrometer observations were used to develop retrievals. The conventional look-up table method (LUT) and random forest method (RF) were applied to the disdrometer data to develop retrievals for the volume-weighted mean diameter (Dm), the shape factor (mu), the normalized intercept parameter (Nw), the ice water content (IWC), and the snowfall rate (S). Evaluations were performed between the D3R radar and disdrometer observations using these two methods. The mean errors of the retrievals based on the RF method were small compared with those of the LUT method. The results indicate that the RF method is a promising way of retrieving microphysical parameters, because this method does not require any assumptions about the PSD of snowfall.

Due to the loss of freedom, the stability and tracking ability of the manipulator around the singularity become worse. This article aims at improving the accuracy of the manipulator and ensuring the stability of the system with the damped reciprocal method. Firstly, the singularities are separated into forearm and wrist singularities to obtain the singular factors of the manipulator respectively. Secondly, a new mathematical function of the approximate damped reciprocal of the singular factor is proposed. Thirdly, the singularities are avoided by modifying the Jacobian matrixes of the manipulator with the approximate damped reciprocal algorithm. Finally, the effectiveness and the stability of the system are proved by the simulations on a manipulator with the spherical wrist. The simulation results prove that this method can largely improve the accuracy of the end-effector and can ensure the stability of the system around the singular region.

A novel phenol-degrading strain was isolated and identified as Rhodococcus ruber C1. The degradation analysis shows that 1806 mg/L of phenol can be completely degraded by strain C1 within 38 h, and the maximum specific growth rate (μmax=1.527 h−1) and maximum specific phenol degradation rate (qmax=3.674 h−1) indicate its excellent phenol metabolism capability. More importantly, phenol can be degraded by strain C1 in the temperature range of 20–45 °C within 72 h, and with longer degradation time, phenol can be completely degraded even at 10, 15 and 50 °C. The whole genome of strain C1 was sequenced, and a comparative genome analysis of strain C1 with 36 other genomes of Rhodococcus was performed. A remarkable gene family expansion occurred during the evolution of Rhodococcus, and a comprehensive evolutionary picture of Rhodococcus at genomic level was presented. Moreover, the copy number of genes involved in phenol metabolism was compared among genus Rhodococcus, and the results demonstrate high phenol degradation capability of strain C1 at genomic level. These findings suggest that Rhodococcus ruber C1 is a bacterium capable of degrading phenol efficiently in the temperature range of 10–50 °C.

We study theoretically the local density of states (DOS) in a topological Josephson junction. We show that the well-known 4π Josephson effect originates from the interference effect between two Majorana fermions (MFs) that are localized at the Josephson junction. In addition, the DOS for electrons (holes) shows the 4π interference information along each parity conserved energy spectrum. The DOS displays a 2π period oscillation when two trivial states interfere with each other. This means that the DOS information may be used to distinguish the MFs from trivial localized states. We suggest that the interference effect and the DOS can be detected by using two STM leads or two normal leads. A single side lead can only detect the Andreev reflection tunneling process in the junction, which cannot reveal information about the interference effect in general. However, using two side leads, we can reveal information about the interference effect of the MFs as well as the DOS by combining Andreev reflection with the electron transmission process.

Snow particle size distribution (PSD) information is important in understanding the microphysics and quantitative precipitation estimation over complex terrain. Measurement and interpretation of the snow PSDs is a topic of active research. This study investigates snow PSDs during 3 year of observations from Parsivel2 disdrometers and precipitation imaging packages (PIP) at five different sites in the PyeongChang region of South Korea. Variabilities in the values of the density of snow (ρ), snowfall rate (S), and ice water content (IWC) are studied. To further understand the characteristics of snow PSD at different density and snowfall rate, the snow particle size distribution measurements are divided into six classes based on the density values of snowfall and five classes based on snowfall rates. The mean shape factors (Dm, log10Nw, and μ) of normalized gamma distribution are also derived based on different density and snowfall rate classes. The Dm decreases and log10Nw and μ increase as the density increases. The Dm and log10Nw increase and μ decreases with the increase of snowfall rate. The power-law relationship between ρ and Dm is obtained and the relationship between S and IWC is also derived.

Inflammatory bowel disease (IBD) is associated with dysregulation of both innate and adaptive immune response in the intestine. MicroRNA (miR)-155 is frequently expressed and functions in many immune cell types. Besides its function in adaptive immunity, miR-155 is a key regulator of the innate immune response in macrophages, dendritic cells, and even in epithelia cells. Although the roles of miR-155 within T and B lymphocytes in colitis have been reported, its function in innate immune cells has not been thoroughly examined. In this study, the dextran sulfate sodium (DSS)-induced colitis model was established in wild-type (WT) and miR-155−/− mice. Our results showed that miR-155 deficiency in macrophages recapitulated the alleviated colitis feature of miR-155−/− mice and appeared to skew toward the alterative M2 phenotype. Notably, the predominance of M2 in colon can result in dampened intestinal immune cell proliferation and inhibit CD4 T cell polarization toward Th1 and Th17. Moreover, C/EBPβ and SOCS1 were demonstrated as two key functional targets in this process. We also provided evidence for use of miR-155 inhibitor to treat colitis. Collectively, the findings highlight the central role of alternative M2 skewing for miR-155 function in colitis and reveal that macrophages might be a main target for therapeutics.

Decidual CD8+ (dCD8) T cells have been proposed to play important roles in immune protection against the invading pathogens and in tolerance toward the growing semi-allogeneic fetus during early pregnancy. However, their phenotypic and functional characteristics remain poorly defined. Here, we performed the first analysis of the transcriptional and alternative splicing (AS) signatures for human first-trimester dCD8 T cells using high-throughput mRNA sequencing. Our data revealed that dCD8 T cells have distinct transcriptional and AS landscapes when compared with their autologous peripheral blood CD8+ (pCD8) T counterparts. Furthermore, human dCD8 T cells were observed to contain CD8-Treg and effector-memory T-cell subsets, and display enhanced functionality in terms of degranulation and cytokine production on a per-cell basis. Additionally, we have identified the novel splice junctions that use a high ratio of the non-canonical splicing motif GC-AG and found that AS is not a major contributor to the gene expression-level changes between paired pCD8 and dCD8 T cells. Together, our findings not only provide a comprehensive framework of the transcriptional and AS landscapes but also reveal the functional feature of human dCD8 T cells, which are of great importance in understanding the biology of these cells and the physiology of human healthy pregnancy.

Decidual CD4+ T (dCD4 T) cells are crucial for the maternal-fetal immune tolerance required for a healthy pregnancy outcome. However, their molecular and functional characteristics are not well elucidated. In this study, we performed the first analysis of transcriptional and alternative splicing (AS) landscapes for paired decidual and peripheral blood CD4+ T (pCD4 T) cells in human early pregnancy using high throughput mRNA sequencing. Our data showed that dCD4 T cells are endowed with a unique transcriptional signature when compared to pCD4 T cells: dCD4 T cells upregulate 1,695 genes enriched in immune system process whereas downregulate 1,011 genes mainly related to mRNA catabolic process and the ribosome. Moreover, dCD4 T cells were observed to be at M phase, and show increased activation, proliferation, and cytokine production, as well as display an effector-memory phenotype and a heterogenous nature containing Th1, Th17, and Treg cell subsets. However, dCD4 T cells undergo a comparable number of upregulated and downregulated AS events, both of which are enriched in the genes related to cellular metabolic process. And the changes at the AS event level do not reflect measurable differences at the gene expression level in dCD4 T cells. Collectively, our findings provide a comprehensive portrait of the unique transcriptional signature and AS profile of CD4+ T cells in human decidua and help us gain more understanding of the functional characteristic of these cells during early pregnancy.