Glucose metabolism reprogramming in gynecologic malignant tumors.

The incidence and mortality of gynecological tumors are progressively increasing due to factors such as obesity, viral infection, unhealthy habits, as well as social and economic pressures. Consequently, it has emerged as a significant threat to women's health. Numerous studies have revealed the remarkable metabolic activity of tumor cells in glycolysis and its ability to influence malignant biological behavior through specific mechanisms. Therefore, it is crucial for patients and gynecologists to comprehend the role of glycolytic proteins, regulatory molecules, and signaling pathways in tumorigenesis, progression, and treatment. This article aims to review the correlation between abnormal glucose metabolism and gynecologic tumors including cervical cancer (CC), endometrial carcinoma (EC), and ovarian cancer (OC). The findings from this research will provide valuable scientific insights for early screening, timely diagnosis and treatment interventions while also aiding in the prevention of recurrence among individuals with gynecological tumors.

Compound heterozygous mutation of the SNX14 gene causes autosomal recessive spinocerebellar ataxia 20.

Objective: The article aims to provide genetic counseling to a family with two children who were experiencing growth and developmental delays. Methods: Clinical information of the proband was collected. Peripheral blood was collected from core family members to identify the initial reason for growth and developmental delays by whole exome sequencing (WES) and Sanger sequencing. To ascertain the consequences of the newly discovered variants, details of the variants detected were analyzed by bioinformatic tools. Furthermore, we performed in vitro experimentation targeting SNX14 gene expression to confirm whether the variants could alter the expression of SNX14. Results: The proband had prenatal ultrasound findings that included flattened frontal bones, increased interocular distance, widened bilateral cerebral sulci, and shortened long bones, which resulted in subsequent postnatal developmental delays. The older sister also displayed growth developmental delays and poor muscle tone. WES identified compound heterozygous variants of c.712A>T (p.Arg238Ter) and .2744A>T (p.Gln915Leu) in the SNX14 gene in these two children. Both are novel missense variant that originates from the father and mother, respectively. Sanger sequencing confirmed this result. Following the guideline of the American College of Medical Genetics and Genomics (ACMG), the SNX14 c.712A>T (p.Arg238Ter) variant was predicted to be pathogenic (P), while the SNX14 c.2744A>T (p.Gln915Leu) variant was predicted to be a variant of uncertain significance (VUS). The structural analysis revealed that the c.2744A>T (p.Gln915Leu) variant may impact the stability of the SNX14 protein. In vitro experiments demonstrated that both variants reduced SNX14 expression. Conclusion: The SNX14 gene c.712A>T (p.Arg238Ter) and c.2744A>T (p.Gln915Leu) were identified as the genetic causes of growth and developmental delay in two affected children. This conclusion was based on the clinical presentations of the children, structural analysis of the mutant protein, and in vitro experimental validation. This discovery expands the range of SNX14 gene variants and provides a foundation for genetic counseling and guidance for future pregnancies in the affected children's families.

Psychometric properties of stigma and discrimination measurement tools for persons living with HIV: a systematic review using the COSMIN methodology.

BACKGROUND: The development of antiretroviral therapy broadly extends the life expectancy of persons living with HIV (PLHIV). However, stigma and discrimination are still great threat to these individuals and the world's public health care system. Accurate and reproducible measures are prerequisites for robust results. Therefore, it is essential to choose an acceptable measure with satisfactory psychometric properties to assess stigma and discrimination. There has been no systematic review of different stigma and discrimination tools in the field of HIV care. Researchers and clinical practitioners do not have a solid reference for selecting stigma and discrimination measurement tools. METHODS: We systematically searched English and Chinese databases, including PubMed, EMBASE, CINAHL, Web of Science, PsycINFO, ProQuest Dissertations and Theses, The Cochrane Library, CNKI,, and Wanfang, to obtain literature about stigma and discrimination measurement tools that have been developed and applied in the field of HIV. The search period was from 1st January, 1996 to 22nd November 2021. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guideline (2018 version) was applied to assess the risk of bias for each involved study and summarize the psychometric properties of each tool. The modified version of the Grading of Recommendations Assessment, Development, and, Evaluation (GRADE) method was used to grade the evidence and develop recommendations. RESULTS: We included 45 studies and 19 PROMs for HIV/AIDS-related stigma and discrimination among PLHIV. All studies had sufficient methodological quality in content validity, structural validity, internal consistency, and the hypothesis testing of structural validity. Limited evidence was found for cross-cultural validity, stability, and criterion validity. No relevant evidence was found concerning measurement error and responsiveness. The Internalized AIDS-related Stigma Scale (IARSS), Internalized HIV Stigma Scale (IHSS), and Wright's HIV stigma scale (WHSS) are recommended for use. CONCLUSIONS: This study recommends three PROMs for different stigma and discrimination scenarios, including IARSS for its good quality and convenience, IHSS for its broader range of items, higher sensitivity, and greater precision, and WHSS for its comprehensive and quick screening. Researchers should also consider the relevance and feasibility of the measurements before putting them into practice. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022308579.

Visualization and Analysis of Infectious Disease Research on Nursing Care Based on CiteSpace in China.

Objective: To analyze the relevant research publications on infectious disease nursing in China to understand the current research status of infectious disease in nursing. Methods: Retrieve relevant literature on infectious disease in nursing from the establishment of the Chinese Biomedical Literature Database, China National Knowledge Infrastructure (CNKI), VIP Database, and Wanfang Database until May 10, 2021. Conduct bibliometric analysis using CiteSpace software. Key words were analyzed using cluster analysis. Results: A total of 4693 relevant literature on infectious disease research in nursing care were included in this study. The overall number of publications on infectious disease research in nursing showed an increasing trend, with a peak in 2010. There were 324 papers funded by scientific research funds, mainly from provincial-level fund projects. The core journal with the most published articles was Nursing Research. The research on infectious disease in nursing mainly focused on various aspects of infectious disease in nursing and infection control. CiteSpace cluster analysis of keywords showed that a total of six clusters were formed: infectious diseases, infectious disease care, health education, mental health, infectious disease nurses, and etiology. After 2015, high-mutation keywords included "quality nursing" and "infection control". Conclusion: Chinese research on infectious disease research in nursing closely follows clinical reality and has developed rapidly. Currently, research focuses on infectious disease research in nursing and infection control. Future research trends will further broaden the depth and breadth of the research, enhance research on infection control and quality nursing, and improve the breadth and depth of the research.

Identification of chromosomal abnormalities in miscarriages by CNV-Seq.

OBJECTIVE: The primary object of this study is to analyze chromosomal abnormalities in miscarriages detected by copy number variants sequencing (CNV-Seq), establish potential pathways or genes related to miscarriages, and provide guidance for birth health in the following pregnancies. METHODS: This study enrolled 580 miscarriage cases with paired clinical information and chromosomal detection results analyzed by CNV-Seq. Further bioinformatic analyses were performed on validated pathogenic CNVs (pCNVs). RESULTS: Of 580 miscarriage cases, three were excluded as maternal cell contamination, 357 cases showed abnormal chromosomal results, and the remaining 220 were normal, with a positive detection rate of 61.87% (357/577). In the 357 miscarriage cases, 470 variants were discovered, of which 65.32% (307/470) were pathogenic. Among all variants detected, 251 were numerical chromosomal abnormalities, and 219 were structural abnormalities. With advanced maternal age, the proportion of numerical abnormalities increased, but the proportion of structural abnormalities decreased. Kyoto Encyclopedia of Genes and Genomes pathway and gene ontology analysis revealed that eleven pathways and 636 biological processes were enriched in pCNVs region genes. Protein-protein interaction analysis of 226 dosage-sensitive genes showed that TP53, CTNNB1, UBE3A, EP300, SOX2, ATM, and MECP2 might be significant in the development of miscarriages. CONCLUSION: Our study provides evidence that chromosomal abnormalities contribute to miscarriages, and emphasizes the significance of microdeletions or duplications in causing miscarriages apart from numerical abnormalities. Essential genes found in pCNVs regions may account for miscarriages which need further validation.

Belief in a just world and organisational loyalty: Trust as an underlying mechanism.

This research examined whether employees' personal belief in a just world (BJW) is associated with their organisational loyalty and whether this relationship is statistically mediated by organisational trust. To test these hypotheses, we conducted two studies with employees from China (study 1, N = 314) and Germany (study 2, N = 189). The results from both studies supported the proposed model. In addition, study 2 revealed that the relationship between BJW and organisational loyalty persisted when controlling for global personality traits. These suggest that managers and organisations may increase employees' loyalty by providing an environment that fosters their sense of justice and trust.

The comprehensive study on the role of POSTN in fetal congenital heart disease and clinical applications.

BACKGROUND: Congenital heart defect (CHD) is the most common congenital abnormality, and it has long been a clinical and public health concern. Our previous findings have found Periostin (POSTN) and Pappalysin-1 (PAPPA) as potential biomarkers for fetal CHD. We aim to further elucidate POSTN's role in fetal heart development and explore the clinical applicability of POSTN and PAPPA as diagnostic marker for fetal CHD. This study is poised to establish a theoretical framework for mitigating the incidence of CHD and advance a novel approach for prenatal screening of fetal CHD. METHODS: We verified differential expression of POSTN and PAPPA in gravida serum and fetal amniotic fluid based on our previous research. We established the Postn knockout mouse by CRISPR/Cas9 to investigate whether Postn deletion leads to cardiac abnormalities in mice. Besides, we explored the mechanism of POSTN on heart development through Postn knockout mouse model and cell experiments. Finally, we established the logistic regression model and decision curve analysis to evaluate the clinical utility of POSTN and PAPPA in fetal CHD. RESULTS: We observed a significant decrease in POSTN and increase in PAPPA in the CHD group. Atrial septal defects occurred in Postn-/- and Postn± C57BL/6 fetal heart, while ventricular septal defects with aortic saddle were observed in Postn± C57BL/6 fetal heart. Disruption of the extracellular matrix (ECM) in cardiomyocytes and multiple abnormalities in cellular sub-organelles were observed in Postn knockout mice. POSTN may positively regulate cell behaviors and unsettle ECM via the TGFß-Smad2/3 signaling pathway. The combination of serum biomarkers POSTN and PAPPA with Echocardiogram can enhance the diagnostic accuracy of CHD. Furthermore, the comprehensive model including POSTN, PAPPA, and two clinical indicators (NT and age) exhibits significantly higher predictive ability than the diagnosis group without the use of serum biomarkers or clinical indicators. CONCLUSIONS: It is the first evidence that Postn deletion leads to cardiac developmental abnormalities in fetal mice. This may involve the regulation of the TGFß signaling pathway. Importantly, POSTN and PAPPA possess clinical utility as noninvasive prenatal promising screening indicators of CHD.

Utilization of solid mine waste in the building materials for 3D printing.

3D printing technology is gradually considered to be a rapid development of a green revolution in the field of architecture. Recently, utilizing solid mine waste to replace natural sand not only greatly reduces the 3D printing costs, but also contributes to an environmental sustainability development. However, most solid waste inevitably has an impact on the inherent mechanical strength and printability of concrete materials. It is an urgent requirement to expand the alternative materials and improve the overall property of 3D concrete materials. This paper reported an innovative concrete material that replaced natural sand with fine limestone powders for 3D concrete printing applications. The experimental measurements were performed including microstructures characteristics, flowability, buildability, shrinkability, layer-interface properties, mechanical properties and interlayer bonding strength. Besides, an effective method was proposed to characterize the printable properties of concrete materials and then the reasonable limestone powder replacement ratio was determined. Based on the investigation results, appropriate substituting limestone powder (40%) can effectively improve the grading of the concrete, thus promoting its printability and buildability. Moreover, the microstructures of the 3D printing concrete materials after curing were denser and their mechanical property improved by approximately 45%. With the further increase of replacement ratio, the reduction in the flowability led to a decrease of the printability. A large number of fine particles increased the shrinkage of the curing process and some bubbles were stranded inside the materials due to its increase in the viscosity, thereby reducing the mechanical properties of the hardened material. The produced concrete for 3D printing can be treated as an eco-friendly building material that contributes to the rational development and resource utilization of solid water, thus promoting the sustainable development of construction field.

Potential factors result in diminished ovarian reserve: a comprehensive review.

The ovarian reserve is defined as the quantity of oocytes stored in the ovary or the number of oocytes that can be recruited. Ovarian reserve can be affected by many factors, including hormones, metabolites, initial ovarian reserve, environmental problems, diseases, and medications, among others. With the trend of postponing of pregnancy in modern society, diminished ovarian reserve (DOR) has become one of the most common challenges in current clinical reproductive medicine. Attributed to its unclear mechanism and complex clinical features, it is difficult for physicians to administer targeted treatment. This review focuses on the factors associated with ovarian reserve and discusses the potential influences and pathogenic factors that may explain the possible mechanisms of DOR, which can be improved or built upon by subsequent researchers to verify, replicate, and establish further study findings, as well as for scientists to find new treatments.

Synergistic effects of hydrogen peroxide and phosphate on uranium(VI) immobilization: implications for the remediation of groundwater at decommissioned in situ leaching uranium mine.

The processes of acid in situ leaching (ISL) uranium (U) mines cause the pollution of groundwater. Phosphate (PO43-) has the potential to immobilize U in groundwater through forming highly insoluble phosphate minerals, but the performance is highly restricted by low pH and high sulfate concentration. In this study, hydrogen peroxide (H2O2) and PO43- were synergistically used for immobilizing U based on the specific properties of groundwater from a decommissioned acid ISL U mine. The removal mechanisms of U and the stability of U on the formed minerals were elucidated by employing X-ray diffraction, scanning electron microscopy, X-ray photoelectron spectroscopy and kinetic experiments. Our results indicated that the removal of U by simultaneously adding H2O2 and PO43- was significantly higher than the removal of U by individually adding H2O2 or PO43-. The removal of U increased with increasing PO43- concentration from 20 to 200 mg L-1 while decreased with increasing H2O2 concentration from 0.003 to 0.3%. Specifically, the removal efficiency of U from groundwater reached 98% after the application of 0.003% H2O2 and 200 mg L-1 PO43-. Amorphous iron phosphate that preferentially formed at low H2O2 and high PO43- concentrations played a dominant role in U removal, while the formations of schwertmannite and crystalline iron phosphates may be also contributed to the removal of U. This was significantly different from the immobilization mechanism of U through the formation of uranyl phosphate minerals after adding phosphate. The kinetic experimental results suggested that the immobilized U had a good stability. Our research may provide a promising method for in situ remediating U-contaminated groundwater at the decommissioned acid ISL U mines.

Preparation of core-shell composite materials capable of slowly releasing phosphate and their remediation performance of uranium-contaminated groundwater.

Acid in-situ leach uranium mining significantly alters the geochemistry of the ore zone, and leaves uranium, residual acid, as well as other potential contaminants in groundwater, which bring harm to human health and ecological environment. Many investigators have been trying to propose remediation strategies for the uranium-contaminated groundwater. Phosphate is an effective immobilization reagent of uranium in the groundwater. However, direct injection of phosphate tends to quickly form precipitates, resulting in fast blockage of the seepage passages in the ore zone around the injection holes and hindering its diffusion. In this paper, HAP@SiO2-600, HAP@SiO2-600@25SA, and HAP@SiO2-600@75SA with core-shell structures were prepared. Their slow-release of phosphate, the effects of pH, contact time, initial uranium concentration, and coexisting ions on their removal rate and efficiency of uranium, and their function of remediating uranium-contaminated groundwater were investigated. It was found that the increase of SA content in the outer layer of HAP@SiO2-600@25SA and HAP@SiO2-600@75SA resulted in the slow release rate of phosphate, decreasing the removal rate of uranium. The adsorption capacities of HAP@SiO2-600, HAP@SiO2-600@25SA, and HAP@SiO2-600@75SA from the aqueous solution at pH = 3.0 and 303 K were up to 582.6, 558.5, and 507.3 mg g-1, respectively. In addition, the materials showed excellent uranium removal performance in experiments where multiple ions coexisted. For actual acidic uranium-contaminated groundwater, HAP@SiO2-600, HAP@SiO2-600@25SA, and HAP@SiO2-600@75SA effectively increased the pH from 2.75 to 4.40, 3.87, and 3.72, respectively, and decreased the uranium concentration from 5.12 to 0.0062, 0.0065, and 0.0058 mg L-1, respectively. The FT-IR, XRD, TEM and XPS characterizations were performed to further clarify the uranium removal mechanism, and it was found that the elimination of U(VI) was ascribed to dissolution-precipitation, adsorption and ion exchange. The results show that the core-shell composite material capable of slowly releasing phosphate is effective in remediating uranium-contaminated groundwater.

Construction of an aging-related risk signature in high-grade serous ovarian cancer for predicting survival outcome and immunogenicity.

Studies have shown that aging significantly impacts tumorigenesis, survival outcome, and treatment efficacy in various tumors, covering high-grade serous ovarian cancer (HGSOC). Therefore, the objective for this investigation is to construct an aging-relevant risk signature for the first time, which will help evaluate the immunogenicity and survival status for patients with HGSOC. Totaling 1727 patients with HGSOC, along with their mRNA genomic data and clinical survival data, were obtained based on 5 independent cohorts. The Lasso-Cox regression model was utilized to identify the aging genes that had the most significant impact on prognosis. The risk signature was developed by integrating the determined gene expression and accordant model weights. Additionally, immunocytes in the microenvironment, signaling pathways, and immune-relevant signatures were assessed based on distinct risk subgroups. Finally, 2 cohorts that underwent treatment with immune checkpoint inhibitor (ICI) were employed to confirm the effects of identified risk signature on ICI efficacy. An aging signature was constructed from 12 relevant genes, which showed improved survival outcomes in low-risk HGSOC patients across discovery and 4 validation cohorts (all P < .05). The low-risk subgroup showed better immunocyte infiltration and higher enrichment of immune pathways and ICI predictors based on further immunology analysis. Notably, in the immunotherapeutic cohorts, low-risk aging signature was observed to link to better immunotherapeutic outcomes and increased response rates. Together, our constructed signature of aging has the potential to assess not only the prognosis outcome and immunogenicity, but also, importantly, the efficacy of ICI treatment. This signature provides valuable insights for prognosis prediction and immunotherapeutic effect evaluation, ultimately promoting individualized treatment for HGSOC patients.

Patient-reported outcome measures of stigma and discrimination for people living with HIV: a systematic review protocol.

OBJECTIVE: The objective of this systematic review is to apply COnsensus-based standards for the selection of health Measurement INstruments (COSMIN) methodology to review psychometric properties of patient-reported outcome measures (PROMs) of HIV-related stigma and/or discrimination. INTRODUCTION: Due to the development of antiretroviral therapy, the life expectancy of people living with HIV is similar to the life expectancy of the rest of the population. However, HIV-related stigma and discrimination are still major barriers to improving the quality of life of persons living with HIV. These barriers are a threat to these individuals and the world's public health care systems. Accurate and reproducible PROMs are prerequisites for robust and reliable results. Therefore, it is important to choose acceptable PROMs with satisfactory psychometric properties to assess HIV-related stigma and/or discrimination. However, there has been no systematic review of HIV-related stigma or discrimination PROMs in the field of HIV care. INCLUSION CRITERIA: All studies including adults (age ≥18 years) living with HIV will be eligible for inclusion in this review. The review will consider studies that report 1 or more psychometric properties of HIV-related stigma and/or discrimination PROMs. We will consider studies conducted in any country or setting published in English or Chinese. METHODS: Nine databases will be searched from January 1, 1996, to the present, including PubMed, Embase, CINAHL, Web of Science, PsycINFO, ProQuest Dissertations and Theses, Cochrane Library, China National Knowledge Infrastructure, and Wanfang. Assessment of methodological quality, data extraction, data synthesis, and assessing certainty in the findings will be conducted using the COSMIN methodology. REVIEW REGISTRATION: PROSPERO CRD42022308579.

Exploring core mental health symptoms among persons living with HIV: A network analysis.

Context: Persons living with HIV (PLWH) commonly experience mental health symptoms. However, little is known about the core mental health symptoms and their relationships. Objective: This study aimed to evaluate the prevalence of various mental health symptoms and to explore their relationships in symptom networks among PLWH. Methods: From April to July 2022, we recruited 518 participants through convenience sampling in Beijing, China, for this cross-sectional study. Forty mental health symptoms, including six dimensions (somatization symptoms, negative affect, cognitive function, interpersonal communication, cognitive processes, and social adaptation), were assessed through paper-based or online questionnaires. Network analysis was performed in Python 3.6.0 to explore the core mental health symptoms and describe the relationships among symptoms and clusters. Results: Of the 40 mental health symptoms, the most common symptoms were fatigue (71.2%), trouble remembering things (65.6%), and uncertainty about the future (64.0%). In the single symptom network, sadness was the most central symptom across the three centrality indices (rS = 0.59, rC = 0.61, rB = 0.06), followed by feeling discouraged about the future (rS = 0.51, rC = 0.57, rB = 0.04) and feelings of worthlessness (rS = 0.54, rC = 0.53, rB = 0.05). In the symptom cluster network, negative affect was the most central symptom cluster across the three centrality indices (rS = 1, rC = 1, rB = 0.43). Conclusion: Our study provides a new perspective on the role of each mental health symptom among PLWH. To alleviate the mental health symptoms of PLWH to the greatest extent possible and comprehensively improve their mental health, we suggest that psychological professionals pay more attention to pessimistic mood and cognitive processes in PLWH. Interventions that apply positive psychology skills and cognitive behavioral therapy may be necessary components for the mental health care of PLWH.

The effectiveness and sustainability of peer support interventions for persons living with HIV: a realist synthesis.

BACKGROUND: Peer support is an important supplement to medical resources for persons living with HIV (PLHIV). However, previous studies have shown mixed results about intervention effects. It is necessary to explain the mechanism of peer support interventions' effectiveness and sustainability to help design more valid peer support interventions. OBJECTIVE: To identify and explain the mechanisms that drive the effectiveness and maintain the sustainability of peer support interventions. METHODS: A preliminary theoretical framework was developed through a scoping review of the grey literature and international project frameworks in five professional websites. We then refined the framework by systematically searching evidence in databases including PubMed, EMBASE, Web of Science, ProQuest, CINAHL, CNKI and Wanfang. Qualitative methods were used to generate codes and themes relating to the studies' context, mechanisms and outcomes. We checked chains of inference (connections) across extracted data and themes through an iterative process. RESULTS: A total of 6345 articles were identified, and 52 articles were retained for final synthesis. The refined theoretical framework presents five areas of peer support, including informational support, instrumental support, emotional support, affiliational support and appraisal support; five types of outcomes that peer support can improve for PLHIV, including physiological outcomes, psychological outcomes, behavioural outcomes, cognitive outcomes and social outcomes; the effectiveness mechanism coding system from peer volunteers and the relationship between peer volunteers and PLHIV; and the sustainability mechanism coding system in terms of peer volunteers, PLHIV and study context. CONCLUSIONS: Given that peer support has huge potential human resources, that is, all the qualified PLHIV, irreplaceable advantages in dealing with barriers to HIV-related discrimination and potential comprehensive benefits for PLHIV, it is necessary to develop and organise more peer support projects for PLHIV. Our study highlights that the expansion of peer support projects should be based on their effectiveness and sustainability. PROSPERO REGISTRATION NUMBER: CRD42022339079.

Human umbilical cord mesenchymal stem cell-derived exosomes carrying miR-1827 downregulate SUCNR1 to inhibit macrophage M2 polarization and prevent colorectal liver metastasis.

microRNA-1827 (miR-1827) is proposed to be enriched in exosomes from mesenchymal stem cells (MSCs-Exos). A recent study has addressed the suppressive effect of exosomes from human umbilical cord mesenchymal stem cells (hUC-MSCs-Exos) on colorectal cancer (CRC) metastasis. Hence, our study aims at investigating whether hUC-MSCs-Exos can modulate the liver metastasis in CRC by mediating miR-1827. Transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) were used to identify hUC-MSCs-Exos. Using gain- and loss-of-function approaches, the expression of miR-1827 and succinate receptor 1 (SUCNR1) was altered. Consequently, the biological functions of CRC cells were assessed by CCK-8 and Transwell assays and macrophage M2 polarization was assayed by flow cytometry. Dual-luciferase reporter assay was applied to clarify interaction between miR-1827 and SUCNR1. CRC cells were incubated with hUC-MSCs-Exos and tumor-bearing mice were injected with hUC-MSCs-Exos to examine the effects on CRC cell growth and metastasis. SUCNR1, lowly expressed in CRC, could promote CRC cell growth and macrophage M2 polarization. miR-1827 could target SUCNR1 and hence suppress the progression and metastasis of CRC. hUC-MSCs-Exos carried miR-1827 to inhibit M2 macrophage polarization by downregulating SUCNR1 expression, and inhibited proliferating, migrating and invading properties of CRC cells. Furthermore, hUC-MSCs-Exos carrying miR-1827 blocked CRC liver metastasis in vivo. These findings indicate hUC-MSCs-Exos as an inhibitor of M2 macrophage polarization and liver metastasis in CRC through inducing miR-1827-targeted inhibition of SUCNR1. This provides a theoretical basis for understanding the mechanisms underlying Exos-based target therapy for CRC.

Authentic leadership and employee resilience during the COVID-19: The role of flow, organizational identification, and trust.

The present work investigated fundamental mediating mechanisms (i.e., flow experience, organizational identification, and trust), underlining the impact of authentic leadership on employee resilience during the turbulent COVID-19 pandemic. A total of 901 frontline employees working in a construction engineering company in China participated in this study. They were asked to respond to a battery of questionnaires comprising Trust Scale (affective-based, cognitive-based, and competence-based), Flow Proneness Questionnaire (FPQ), Organizational Identification Scale, Authentic Leadership Questionnaire, and Employee Resilience Scale. Results of structural equation modeling indicated that: (1) Authentic leadership positively predicted employee resilience in the COVID-19 pandemic, directly and indirectly. (2) As for the indirect relationship, two parallel mediation effects and one chain mediation were detected: employees' flow at work and organizational identification respectively and dependently mediated the relationship between authentic leadership and employee resilience; trust and organizational identification played as a chain mediation role within authentic leadership-employee resilience association. The study provides empirical evidence for organizations' resilience-building and leadership training programs. Findings also contribute to the literature by facilitating flow intervention, promoting organizational identification and trust to enhance the effect of authentic leadership in promoting positive psychological functioning of employee resilience. Limitations with respect to future research directions were also outlined.

Genetic characteristics of suspected retinitis pigmentosa in a cohort of Chinese patients.

The study aimed to screen for the causative variants in Chinese patients with suspected retinitis pigmentosa (RP). A cohort of 75 unrelated Chinese patients with a clinical diagnosis of RP and their available family members were enrolled in this study. Genomic DNA of all subjects was extracted and whole-exome sequencing (WES) was applied. Candidate variants were identified, and minigene assays were conducted to evaluate the pathogenicity of novel splicing variants. Totally, the diagnostic yield was 44 % (33/75) and 16 novel variants that had not been reported previously were found. Among the genetically solved 33 cases, 31 patients were identified as carrying causative variants of RP and 2 patients carried pathogenic variants implicated in other retinal diseases. USH2A, CYP4V2, and RPGR were the most common causative genes, accounting for about half of the genetically solved cases. Moreover, minigene assays validated that the novel splicing variants were detrimental. Additionally, 9 patients carried a single deleterious heterozygous variant in 6 genes with autosomal recessive hereditary patterns, and no corresponding copy number variants (CNVs) was detected. The findings of this study revealed the genetic landscape of RP in China and provided guidance for clinicians.

Identification of Gravida Serum Biomarkers for Noninvasive Prenatal Diagnosis Fetal Congenital Heart Disease.

Congenital heart disease (CHD) is well established as the most common congenital defect worldwide. Given the lack of biomarkers available, we aimed to identify new biomarkers for the noninvasive prenatal diagnosis of fetal CHD. This study used data-independent acquisition (DIA) to explore potential protein biomarkers that co-expressed in gravida serum (GS) and fetal amniotic fluid (AF). Next, parallel reaction monitoring (PRM), enzyme-linked immunosorbent assay (ELISA), receiver operating characteristic curve (ROC) analysis, and the immunohistochemistry (IHC) were performed to validate the potential biomarkers. Based on DIA and PRM proteomics and bioinformatics results, we identified POSTN and PAPPA in GS as candidate biomarkers. Their differential expression during ELISA and IHC were generally consistent with our proteomics results. POSTN combined with PAPPA in GS yield a good diagnose fetal CHD with sensitivity of 83.9%, specificity of 73.9%, and an area under curve (AUC) of 0.842. This is the first study showing that POSTN in GS and AF is associated with fetal CHD. POSTN and PAPPA have huge prospects for application as potential biomarkers in the noninvasive prenatal diagnosis of fetal CHD. Congenital heart disease (CHD) is well-established as the most common congenital defect worldwide. Given the lack of biomarkers available, we aimed to identify new biomarkers for the noninvasive prenatal diagnosis of fetal CHD. We used data independent acquisition (DIA) to explore potential protein biomarkers that co-expressed in gravida serum (GS) and fetal amniotic fluid (AF). Next, parallel reaction monitoring (PRM), enzyme-linked immunosorbent assay (ELISA), receiver operating characteristic curve (ROC) analysis, and the immunohistochemistry (IHC) were performed to validate the potential biomarkers. Based on DIA and PRM proteomics and bioinformatics results, we identified POSTN and PAPPA in GS as candidate biomarkers. Their differential expression during ELISA and IHC were generally consistent with our proteomics results. POSTN combined with PAPPA in GS yield a good diagnose fetal CHD with sensitivity of 83.9 %, specificity of 73.9%, and an area under curve (AUC) of 0.842. This is the first study showing that POSTN in GS and AF is associated with fetal CHD. POSTN and PAPPA have huge prospects for application as potential biomarkers in the noninvasive prenatal diagnosis of fetal CHD.

Identification of Hub Genes Associated with Progression and Prognosis of Bladder Cancer by Integrated Bioinformatics Analysis.

BACKGROUND: Bladder cancer (BLCA) is an extremely common carcinoma of the urinary system that has a high incidence of relapse. Although intensive studies have investigated its pathology in the past decades, there are significant knowledge gaps regarding the characterization of the molecular processes underlying the progression of disease and consequently its prognosis. The purpose of current research was to identify significant genes that could serve as prognostic and progression biomarkers. METHODS: Gene expression profiles were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Differential gene expression analysis (DGEA) and weighted gene co-expression network analysis (WGCNA) were conducted to recognize differential co-expression genes. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to explore gene function. Moreover, protein-protein interactions (PPI) network, overall survival (OS) and disease-free survival (DFS) were used to identify survival-related hub genes. Additionally, associations between these gene's expression and clinical parameters were determined. Finally, the Human Protein Atlas (HPA) database and qRT-PCR were used to validate gene's expression. RESULTS: About 124 differential co-expression genes were identified. These genes were mainly enriched in muscle system process and muscle contraction (biological process, BP), contractile fiber, myofibril, sarcomere, focal adhesion and cell-substrate junction (cellular component, CC) and actin binding (molecular function, MF) in GO enrichment analysis, while enriched in vascular smooth muscle contraction, focal adhesion, cardiac muscle contraction, hypertrophic cardiomyopathy, dilated cardiomyopathy and regulation of actin cytoskeleton in KEGG analysis. Furthermore, five survival-related hub genes (MYH11, ACTA2, CALD1, TPM1, MYLK) were identified via OS and DFS. In addition, these survival-related gene's expression was correlated with grade, stage and TNM stage. Finally, all survival-related hub genes were determined to be down-regulated in BLCA tissues by qRT-PCR and HPA databases. CONCLUSIONS: Our current study verified five new key genes in BLCA, which may participate in the prognosis and progression and serve as novel biomarkers of BLCA.