Tumor-polarized GPX3+ AT2 lung epithelial cells promote premetastatic niche formation.

The cellular and molecular components required for the formation of premetastatic niche (PMN) to promote lung metastasis need to be further investigated. Lung epithelial cells have been reported to exhibit immunomodulatory roles in lung homeostasis and also to mediate immunosuppressive PMN formation in lung metastasis. Here, by single-cell sequencing, we identified a tumor-polarized subpopulation of alveolar type 2 (AT2) epithelial cells with increased expression of glutathione peroxidase 3 (GPX3) and high production of interleukin (IL)-10 in the PMN. IL-10-producing GPX3+ AT2 cells inhibited CD4+ T cell proliferation but enhanced regulatory T cell generation. Mechanistically, tumor exosome-inducing GPX3 expression is required for GPX3+ AT2 cells to preferentially produce IL-10 by stabilizing hypoxia-inducible factor 1 (HIF-1α) and promoting HIF-1α-induced IL-10 production. Accordingly, conditional knockout of GPX3 in AT2 cells suppressed lung metastasis in spontaneous metastatic models. Together, our findings reveal a role of tumor-polarized GPX3+ AT2 cells in promoting lung PMN formation, adding insights into immune evasion in lung metastasis and providing potential targets for the intervention of tumor metastasis.

Joint Modeling of Gene-Environment Correlations and Interactions Using Polygenic Risk Scores in Case-Control Studies.

Polygenic risk scores (PRS) are rapidly emerging as a way to measure disease risk by aggregating multiple genetic variants. Understanding the interplay of PRS with environmental factors is critical for interpreting and applying PRS in a wide variety of settings. We develop an efficient method for simultaneously modeling gene-environment correlations and interactions using PRS in case control studies. We use a logistic-normal regression modeling framework to specify the disease risk and PRS distribution in the underlying population and propose joint inference across the two models using the retrospective likelihood of the case-control data. Extensive simulation studies demonstrate the flexibility of the method in trading-off bias and efficiency for the estimation of various model parameters compared to the standard logistic regression or a case-only analysis for gene-environment interactions, or a control-only analysis for gene-environment correlations. Finally using simulated case-control data sets within the UK Biobank study, we demonstrate the power of our method for its ability to recover results from the full prospective cohort for the detection of an interaction between long-term oral contraceptive use and PRS on the risk of breast cancer. This method is computationally efficient and implemented in a user-friendly R package.

TMPRSS13 promotes the cell entry of swine acute diarrhea syndrome coronavirus.

Swine acute diarrhea syndrome coronavirus (SADS-CoV) has caused severe intestinal diseases in pigs. It originates from bat coronaviruses HKU2 and has a potential risk of cross-species transmission, raising concerns about its zoonotic potential. Viral entry-related host factors are critical determinants of susceptibility to cells, tissues, or species, and remain to be elucidated for SADS-CoV. Type II transmembrane serine proteases (TTSPs) family is involved in many coronavirus infections and has trypsin-like catalytic activity. Here we examine all 18 members of the TTSPs family through CRISPR-based activation of endogenous protein expression in cells, and find that, in addition to TMPRSS2 and TMPRSS4, TMPRSS13 significantly facilitates SADS-CoV infection. This is confirmed by ectopic expression of TMPRSS13, and specific to trypsin-dependent SADS-CoV. Infection with pseudovirus bearing SADS-CoV spike protein indicates that TMPRSS13 acts at the entry step and is sensitive to serine protease inhibitor Camostat. Moreover, both human and pig TMPRSS13 are able to enhance the cell-cell membrane fusion and cleavage of spike protein. Overall, we demonstrate that TMPRSS13 is another host serine protease promoting the membrane-fusion entry of SADS-CoV, which may expand its host tropism by using diverse TTSPs.

Quantum phase transitions in two-dimensional superconductors: a review on recent experimental progress.

Superconductor-insulator/metal transition (SMT) as a paradigm of quantum phase transition has been a research highlight over the last three decades. Benefit from recent developments in the fabrication and measurements of two-dimensional (2D) superconducting films and nanodevices, unprecedented quantum phenomena have been revealed in the quantum phase transitions of 2D superconductors. In this review, we introduce the recent progress on quantum phase transitions in 2D superconductors, focusing on the quantum Griffiths singularity (QGS) and anomalous metal state. Characterized by a divergent critical exponent when approaching zero temperature, QGS of SMT is discovered in ultrathin crystalline Ga films and subsequently detected in various 2D superconductors. The universality of QGS indicates the profound influence of quenched disorder on quantum phase transitions. Besides, in a 2D superconducting system, whether a metallic ground state can exist is a long-sought mystery. Early experimental studies indicate an intermediate metallic state in the quantum phase transition of 2D superconductors. Recently, in high-temperature superconducting films with patterned nanopores, a robust anomalous metal state (i.e. quantum metal or Bose metal) has been detected, featured as the saturated resistance in the low temperature regime. Moreover, the charge-2equantum oscillations are observed in nanopatterned films, indicating the bosonic nature of the anomalous metal state and ending the debate on whether bosons can exist as a metal. The evidences of the anomalous metal states have also been reported in crystalline epitaxial thin films and exfoliated nanoflakes, as well as granular composite films. High quality filters are used in these works to exclude the influence of external high frequency noises in ultralow temperature measurements. The observations of QGS and metallic ground states in 2D superconductors not only reveal the prominent role of quantum fluctuations and dissipations but also provide new perspective to explore quantum phase transitions in superconducting systems.

Integrated machine learning identifies epithelial cell marker genes for improving outcomes and immunotherapy in prostate cancer.

BACKGROUND: Prostate cancer (PCa), a globally prevalent malignancy, displays intricate heterogeneity within its epithelial cells, closely linked with disease progression and immune modulation. However, the clinical significance of genes and biomarkers associated with these cells remains inadequately explored. To address this gap, this study aimed to comprehensively investigate the roles and clinical value of epithelial cell-related genes in PCa. METHODS: Leveraging single-cell sequencing data from GSE176031, we conducted an extensive analysis to identify epithelial cell marker genes (ECMGs). Employing consensus clustering analysis, we evaluated the correlations between ECMGs, prognosis, and immune responses in PCa. Subsequently, we developed and validated an optimal prognostic signature, termed the epithelial cell marker gene prognostic signature (ECMGPS), through synergistic analysis from 101 models employing 10 machine learning algorithms across five independent cohorts. Additionally, we collected clinical features and previously published signatures from the literature for comparative analysis. Furthermore, we explored the clinical utility of ECMGPS in immunotherapy and drug selection using multi-omics analysis and the IMvigor cohort. Finally, we investigated the biological functions of the hub gene, transmembrane p24 trafficking protein 3 (TMED3), in PCa using public databases and experiments. RESULTS: We identified a comprehensive set of 543 ECMGs and established a strong correlation between ECMGs and both the prognostic evaluation and immune classification in PCa. Notably, ECMGPS exhibited robust predictive capability, surpassing traditional clinical features and 80 published signatures in terms of both independence and accuracy across five cohorts. Significantly, ECMGPS demonstrated significant promise in identifying potential PCa patients who might benefit from immunotherapy and personalized medicine, thereby moving us nearer to tailored therapeutic approaches for individuals. Moreover, the role of TMED3 in promoting malignant proliferation of PCa cells was validated. CONCLUSIONS: Our findings highlight ECMGPS as a powerful tool for improving PCa patient outcomes and supply a robust conceptual framework for in-depth examination of PCa complexities. Simultaneously, our study has the potential to develop a novel alternative for PCa diagnosis and prognostication.

Diet supplementation of organic zinc positively affects growth, antioxidant capacity, immune response and lipid metabolism in juvenile largemouth bass, Micropterus salmoides.

Zn is an important trace element involved in various biochemical processes in aquatic species. An 8-week rearing trial was thus conducted to investigate the effects of Zn on juvenile largemouth bass (Micropterus salmoides) by feeding seven diets, respectively, supplemented with no Zn (Con), 60 and 120 mg/kg inorganic Zn (Sul60 and Sul120), and 30, 60, 90 and 120 mg/kg organic Zn (Bio30, Bio60, Bio90 and Bio120). Sul120 and Bio120 groups showed significantly higher weight gain and specific growth rate than Con group, with Bio60 group obtaining the lowest viscerosomatic index and hepatosomatic index. 60 or 90 mg/kg organic Zn significantly facilitated whole body Zn retention. Up-regulation of hepatic superoxide dismutase, glutathione peroxidase and catalase activities and decline of malondialdehyde contents indicated augmented antioxidant capacities by organic Zn. Zn treatment also lowered plasma aminotransferase levels while promoting acid phosphatase activity and hepatic transcription levels of alp1, acp1 and lyz-c than deprivation of Zn. The alterations in whole body and liver crude lipid and plasma TAG contents illustrated the regulatory effect of Zn on lipid metabolism, which could be possibly attributed to the changes in hepatic expressions of acc1, pparγ, atgl and cpt1. These findings demonstrated the capabilities of Zn in potentiating growth and morphological performance, antioxidant capacity, immunity as well as regulating lipid metabolism in M. salmoides. Organic Zn could perform comparable effects at same or lower supplementation levels than inorganic Zn, suggesting its higher efficiency. 60 mg/kg supplementation of organic Zn could effectively cover the requirements of M. salmoides.

LncRNA Malat1 inhibition of TDP43 cleavage suppresses IRF3-initiated antiviral innate immunity.

Long noncoding RNAs (lncRNAs) involved in the regulation of antiviral innate immune responses need to be further identified. By functionally screening the lncRNAs in macrophages, here we identified lncRNA Malat1, abundant in the nucleus but significantly down-regulated after viral infection, as a negative regulator of antiviral type I IFN (IFN-I) production. Malat1 directly bound to the transactive response DNA-binding protein (TDP43) in the nucleus and prevented activation of TDP43 by blocking the activated caspase-3-mediated TDP43 cleavage to TDP35. The cleaved TDP35 increased the nuclear IRF3 protein level by binding and degrading Rbck1 pre-mRNA to prevent IRF3 proteasomal degradation upon viral infection, thus selectively promoting antiviral IFN-I production. Deficiency of Malat1 enhanced antiviral innate responses in vivo, accompanying the increased IFN-I production and reduced viral burden. Importantly, the reduced MALAT1, augmented IRF3, and increased IFNA mRNA were found in peripheral blood mononuclear cells (PBMCs) from systemic lupus erythematosus (SLE) patients. Therefore, the down-regulation of MALAT1 in virus-infected cells or in human cells from autoimmune diseases will increase host resistance against viral infection or lead to autoinflammatory interferonopathies via the increased type I IFN production. Our results demonstrate that the nuclear Malat1 suppresses antiviral innate responses by targeting TDP43 activation via RNA-RBP interactive network, adding insight to the molecular regulation of innate responses and autoimmune pathogenesis.

IMIX: a multivariate mixture model approach to association analysis through multi-omics data integration.

MOTIVATION: Integrative genomic analysis is a powerful tool used to study the biological mechanisms underlying a complex disease or trait across multiplatform high-dimensional data, such as DNA methylation, copy number variation and gene expression. It is common to perform large-scale genome-wide association analysis of an outcome for each data type separately and combine the results ad hoc, leading to loss of statistical power and uncontrolled overall false discovery rate (FDR). RESULTS: We propose a multivariate mixture model (IMIX) framework that integrates multiple types of genomic data and allows modeling of inter-data-type correlations. We investigated the across-data-type FDR control in IMIX and demonstrated lower misclassification rates at controlled overall FDR than established individual data type analysis strategies, such as the Benjamini-Hochberg FDR control, the q-value and the local FDR control by extensive simulations. IMIX features statistically principled model selection, FDR control and computational efficiency. Applications to The Cancer Genome Atlas data provided novel multi-omics insights into the genes and mechanisms associated with the luminal and basal subtypes of bladder cancer and the prognosis of pancreatic cancer. AVAILABILITYAND IMPLEMENTATION: We have implemented our method in R package 'IMIX' available at https://github.com/ziqiaow/IMIX, as well as CRAN soon. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Clinical characteristics of IgG4-related respiratory disease patients: a large Chinese cohort study.

OBJECTIVES: IgG4-related disease (IgG4-RD) is an autoimmune disorder and frequently involves multiple organs. The respiratory tract is one of the most frequently affected sites. In this study, we aimed to compare the demographic and clinical characteristics between IgG4 related respiratory disease (IgG4-RRD+) and extra-thoracic IgG4-related disease (IgG4-RRD-) in a large cohort. METHODS: A total of 448 cases of IgG4-RD (104 IgG4-RRD+ patients and 344 IgG4-RRD- patients) diagnosed at Peking University People's Hospital during 2003 to 2020 were included in our study. Patients' demographic data, clinical characteristics, laboratory parameters and imaging features were analysed. RESULTS: IgG4-RRD+ patients had an older age at disease onset and diagnosis. Multiorgan involvement and hypocomplementaemia were more common in IgG4-RRD+. Besides, the level of ESR, IgG and IgG4 were higher in IgG4-RRD+ patients. In IgG4-RRD+ group, salivary gland, lacrimal gland, lymph nodes, biliary system and kidney were more commonly involved than those in the IgG4-RRD- group. Also, more organ involvement eosinophilia and biliary involvement were independent risk factors for the development of IgG4-RRD+. CONCLUSIONS: Our study revealed demographic, clinical and laboratory differences between the two phenotypes, in addition to describing the imaging features of IgG4-RRD+, which will be helpful for understanding of the disease.

Identifying spatial influence of urban elements on road-deposited sediment and the associated phosphorus by coupling Geodetector and Bayesian Networks.

Elevated particles and phosphorus washed from road-deposited sediment (RDS) are noteworthy causes of eutrophication in urban water bodies. Identifying how urban elements (e.g., dwellings, roads) spatially influence RDS and the associated phosphorus can help pinpoint the primary management areas for RDS pollution and therefore effectively mitigate this problem. This study investigated spatial influence of urban elements on RDS build-up load and phosphorus load in Hanyang district of Wuhan city in central China. Bayesian Networks (BNs), combined with geographical detector (Geodetector) and correlation analysis, were applied to quantify spatial association between kernel density of urban elements, RDS build-up load and phosphorus load in RDS. Results showed that (1) areas with higher density of factories related elements usually had elevated level of RDS build-up load, aluminum-bound phosphorus (Al-P), occluded phosphorus (Oc-P), organophosphorus (Or-P). Higher load of RDS associated iron-bound phosphorus (Fe-P) and apatite phosphorus (Ca-P) usually occurred where dwellings, catering, and entertainment related elements were concentrated. (2) Urban elements mainly showed positive correlation with RDS build-up load, Fe-P, Ca-P, De-P (detrital apatite phosphorus), while they chiefly showed negative correlation with Ex-P (exchangeable phosphorus), Al-P, Oc-P, and Or-P. Bus stations, dwellings, and factories related elements had relatively strong determinant power over spatial stratified heterogeneity of RDS and RDS-associated phosphorus. (3) Geodetector and correlation analysis could boost factors filtering and construction of network structures in the process of developing BNs models. The developed BNs resulted in sound prediction of <150 µm RDS build-up load and phosphorus load, given that the prediction accuracy of models ranged from 0.532 to 0.657. These findings demonstrate that urban elements are useful spatial predictors of RDS pollution, and coupling Geodetector and BNs is promising in RDS pollution prediction and supporting urban nonpoint source pollution management.

Effects of Dietary Carbohydrate Levels on Growth Performance, Body Composition, Antioxidant Capacity, Immunity, and Liver Morphology in Oncorhynchus mykiss under Cage Culture with Flowing Freshwater.

The purpose of this study is to investigate the effects of dietary carbohydrate levels on growth performance, body composition, antioxidant capacity, immunity, and liver morphology in Oncorhynchus mykiss under cage culture with flowing freshwater. Fish (initial body weight 25.70 ± 0.24 g) were fed five isonitrogenous (420 g/kg protein) and isolipidic (150 g/kg lipid) diets containing 50.6, 102.1, 151.3, 200.9 and 251.8 g/kg carbohydrate levels, respectively. The results indicated that fish fed diets containing 50.6-200.9 g/kg carbohydrate showed significantly higher growth performance, feed utilization, and feed intake than those fed 251.8 g/kg dietary carbohydrate levels. Based on the analysis of the quadratic regression equation for weight gain rate, the appropriate dietary carbohydrate requirement of O. mykiss was estimated to be 126.2 g/kg. 251.8 g/kg carbohydrate level activated Nrf2-ARE signaling pathway, suppressed superoxide dismutase activity and total antioxidant capacity, and increased MDA content in the liver. Besides, fish fed a diet containing 251.8 g/kg carbohydrate showed a certain degree of hepatic sinus congestion and dilatation in the liver. Dietary 251.8 g/kg carbohydrate upregulated the mRNA transcription level of proinflammatory cytokines and downregulated the mRNA transcription level of lysozyme and complement 3. Whole-body compositions were not affected by dietary carbohydrate levels. In conclusion, 251.8 g/kg carbohydrate level suppressed the growth performance, antioxidant capacity and innate immunity, resulting in liver injury and inflammatory response of O. mykiss. A diet containing more than 200.9 g/kg carbohydrate is not efficiently utilized by O. mykiss under cage culture with flowing freshwater.

Clinical features of IgG4-related retroperitoneal fibrosis among 407 patients with IgG4-related disease: a retrospective study.

OBJECTIVES: IgG4-related disease (IgG4-RD) is recently recognized as a fibro-inflammatory condition featured by tumefactive lesions in multiple organs, and the retroperitoneum is one of the common involved sites. We undertook this study to compare detailed demographic, clinical and laboratory characteristics of IgG4-RD patients with retroperitoneum lesion (IgG4-RD RPF+) and retroperitoneum free IgG4-RD (IgG4-RD RPF-) in a large cohort. METHODS: We carried out a retrospective review of the medical records of 407 cases of IgG4-RD diagnosed at Peking University People's Hospital between March 2009 and May 2019. RESULTS: Among 407 patients, 58 had retroperitoneum affected. As compared with IgG4-RD RPF- patients, IgG4-RD RPF+ patients showed older age at disease onset and diagnosis. IgG4-RD RPF+ group involved more male patients. In terms of organ involvement, IgG4-RD RPF+ group was more frequently presented with kidney involvement, while salivary gland, lacrimal gland and pancreas were more prominent in the IgG4-RD RPF- group. In addition, the CRP, ESR level and creatinine level were significantly higher in IgG4-RD RPF+ patients, and hypocomplementemia were more common in this group. CONCLUSION: We have revealed demographic, clinical and laboratory differences between IgG4-RD RPF+ and RPF- patients, which indicated potential differences in pathogenesis and important implications for the diagnosis and management of these two phenotypes.

Relapse predictors and serologically unstable condition of IgG4-related disease: a large Chinese cohort.

OBJECTIVES: Patients with IgG4-related disease (IgG4-RD) typically respond well to initial glucocorticoid therapy, but always relapse with tapered or maintenance dosage of steroid. We aimed to identify the risk factors for relapse of IgG4-RD and explore the impact of active intervention on the serologically unstable condition. METHODS: We performed a retrospective study of 277 IgG4-RD patients at Peking University People's Hospital from February 2012 through February 2019. They were all followed for >4 months. The primary outcome was patient relapse. Data on recurrence of IgG4-RD symptoms, laboratory and image findings were recorded, along with information on treatment in the serologically unstable condition. RESULTS: The cumulative relapse rate was 12.86%, 27.84% and 36.1% at 12, 24 and 36 months, respectively. Younger age at onset, younger age at diagnosis, longer time from diagnosis to treatment and history of allergy were associated with relapse. Identified independent risk factors were longer time from diagnosis to treatment and history of allergy. When serum IgG4 level was 20%, 50% or 100% higher than that of the remission period, similar percentages of patients finally relapsed, regardless of whether they were in the immunosuppression intensified or non-intensified group. Median duration from serum IgG4 level instability to relapse in the intensified and non-intensified group was not statistically different. CONCLUSION: The risk factors of relapse were longer time from diagnosis to treatment and history of allergy. Intervention in the serologically unstable condition was not helpful for reducing relapse rate.

Effect of Cu(II) on Mn(II) Oxidation by Free Chlorine To Form Mn Oxides at Drinking Water Conditions.

The chemical oxidation of dissolved Mn(II) to Mn(III/IV) oxides (MnOx) can lead to the accumulation of Mn deposits in drinking water distribution systems. However, Mn(II) oxidation by free chlorine is quite slow under mild conditions (e.g., pH 7.7 and 1.0 mg/L Cl2). This study found a significant role for Cu(II) in Mn(II) oxidation under conditions relevant to the supply of chlorinated drinking water. At pH 7.7, dissolved Cu(II) accelerated Mn(II) oxidation more than 10 times with a dose of 20 µg/L. Solid characterization revealed that during Mn(II) oxidation, Cu(II) adsorbed to freshly formed MnOx and produced Mn-Cu mixtures (denoted as MnOx-Cu(II)). An autocatalytic model for the reaction kinetics suggested that the freshly formed MnOx-Cu(II) had a much higher catalytic activity than that of pure MnOx. Solid CuO also catalyzed Mn(II) oxidation, and kinetic modeling indicated that after an initial oxidation of Mn(II) facilitated by the CuO surface, the freshly formed MnOx-Cu(II) on CuO surface played the dominant role in accelerating further Mn(II) oxidation. This study indicates a high potential for the formation of Mn oxides at locations in a drinking water distribution system or in premise plumbing where both Mn(II) and Cu(II) are available. It provides insights into the co-occurrence of other metals with Mn deposits that is frequently observed in distribution systems.

Detection of Bosonic Mode as a Signature of Magnetic Excitation in One-Unit-Cell FeSe on SrTiO3.

A "fingerprint" of Cooper pairing mediated by collective bosonic excitation mode is the reconstruction of the quasiparticle-density-of-states (DOS) spectrum with an additional "dip-hump" structure located outside the superconducting coherence peak. Here, we report an in situ scanning tunneling spectroscopy study of one-unit-cell (1-UC) FeSe film on a SrTiO3(001) substrate. In the quasiparticle-DOS spectrum, the bosonic excitation mode characterized by the dip-hump structure is detected outside the larger superconducting gap. Statistically, the excitation mode shows an anticorrelation with pairing strength in magnitude and yields an energy scale upper-bounded by twice the superconducting gap. The observation coincides with the characteristics of magnetic resonance in cuprates and iron-based superconductors. Furthermore, the local response of superconducting spectra to magnetically distinct Se defects all exhibits the induced in-gap quasiparticle bound states, indicating an unconventional sign-reversing pairing over the Fermi surface in 1-UC FeSe. These results clarify the magnetic nature of the bosonic excitation mode and reveal a signature of electron-magnetic-excitation coupling in 1-UC FeSe/SrTiO3(001) besides the previously established pairing channel of electron-phonon interaction.

A genetic variant within MDM4 3'UTR miRNA binding site is associated with HPV16-positive tumors and survival of oropharyngeal cancer.

As mouse double minute 4 (MDM4) and HPV16 E6 oncoproteins play important roles in inhibition of p53 activity, a functional polymorphism (rs4245739) in the 3' untranslated regions of MDM4 targeted by microRNA-191 may alter its expression level or functional efficiency, thus affecting tumor status and survival in human papillomavirus (HPV)-positive squamous cell carcinoma of oropharynx (SCCOP). A total of 564 incident SCCOP patients with definitive radiotherapy were included for determination of tumor HPV16 status and genotypes of the polymorphism. Univariate and multivariable Cox models were performed to assess the associations between the polymorphism and outcomes. We found that MDM4 rs4245739 had statistically significant associations with tumor HPV-positivity and survival of SCCOP patients. Patients with AC/CC variant genotypes of MDM4 rs4245739 were approximately 3-fold more likely to be HPV16-positive tumors among SCCOP patients compared with common homozygous AA genotype (adjusted odds ratio = 3.2, 95% confidence interval = 1.9-5.5). Moreover, patients with MDM4 rs4245739 AC/CC variant genotypes had significantly better overall, disease-specific, and disease-free survival compared with those with the corresponding common homozygous AA genotype (all log-rank = P < .05); and these genotypes were significantly associated with an approximately three to four times reduced risk of overall death, death owing to disease, and recurrence after multivariable adjustment. Finally, the significant effects of MDM4 rs4245739 polymorphism on survival were found among HPV16-positive SCCOP patients only after the stratified analyses by tumor HPV status. We concluded that MDM4 rs4245739 polymorphism is significantly associated with tumor HPV status and survival of SCCOP, especially in HPV16-positive SCCOP patients treated with definitive radiotherapy; nevertheless, prospective larger studies are warranted.

Spectroscopic Imaging of Quasiparticle Bound States Induced by Strong Nonmagnetic Scatterings in One-Unit-Cell FeSe/SrTiO_{3}.

The absence of holelike Fermi pockets in the heavily electron-doped iron selenides (HEDISs) challenges the s_{±}-wave pairing originally proposed for iron pnictides, which consists of opposite signs of the gap function on electron and hole pockets. While the HEDIS compounds have been investigated extensively, a consistent description of the superconducting pairing therein is still lacking. Here, by in situ scanning tunneling spectroscopy and theoretical calculations, we study the effects of strong scatterings from nonmagnetic Pb adatoms on the epitaxially grown HEDIS, one-unit-cell FeSe/SrTiO_{3}(001). Systematic tunneling spectra measured on the Pb adatoms show comprehensive signals of quasiparticle bound states, which can be well explained theoretically within the sign-reversing pairing scenarios. The finding implies that, in addition to previously detected phonons, spin fluctuations play an important role in driving the Cooper pairing in FeSe/SrTiO_{3}(001). The sign reversal in the gap function we revealed here is a significant ingredient in a unified understanding of the high-temperature superconductivity in HEDISs.

Analysing the influencing factors of on-line studying engagement of preparatory international students: A case study of the science and technology Chinese course.

With the rapid development of network technology, cross-regional on-line higher education is becoming one of the mainstream directions of distance education development. The effectiveness of on-line studying is significantly influenced by the level of learning engagement, and research on this topic can help learners by providing them with process-oriented learning support and targeted teaching interventions. Using the example of on-line Science and Technology Chinese Course for preparatory international students at four universities in China, this study collected self-reported data from 463 students using a survey method. The questionnaire was divided into two parts: the on-line studying engagement scale and the factors influencing on-line studying engagement. Descriptive statistical analysis and differential testing were conducted on the data using SPSS software, and the structural validity of the questionnaire was tested using AMOS software. With the assistance of Smart PLS, a model of the influencing factors of on-line studying engagement was constructed to explore the relationship between on-line studying engagement and its influencing factors. The study found that: The overall level of engagement in on line studying for preparatory international students is above average. In demographic factors, apart from gender, all other variables have a significant impact on on-line studying. Student-level factors will have a more significant positive impact on the degree of on-line studying engagement of preparatory international students. Among them, academic self-efficacy, basic psychological needs satisfaction, the difficulty of the on-line course, and completion of the assignment have a significant positive effect. The influence of teacher-level factors on behavioral engagement and emotional engagement is stronger than that of student-level factors. However, the emotional support of teacher-level factors, the on-line environment of environmental-level factors, and the perceived usefulness of technology of teacher-level factors have a certain negative impact on engagement in online studying. According to the research results, this paper puts forward the optimization strategies of accelerating the update frequency of Chinese learning materials, strengthening the input of on-line emotional support, and holding language learning activities with cultural characteristics. This study makes an in-depth analysis of the influencing factors of preparatory international students' on-line Chinese studying engagement, and puts forward the optimization strategies to improve the quality of on-line studying, to provide theoretical and practical reference for the development of cross-regional on-line higher education.

Comparative efficacy of commercial oral poly-herbal traditional Chinese medicine formulations combined with western medicine in benign prostatic hyperplasia management: a systematic review and network meta-analysis.

Background: Benign prostatic hyperplasia (BPH) is prevalent among the aging male population and often presents with distressing lower urinary tract symptoms. There is emerging evidence that commercial oral poly-herbal traditional Chinese medicine (TCM) formulation combined with Western medicine (WM) may offer enhanced therapeutic effects compared to WM alone in BPH treatment. Nevertheless, determining the optimal formulations for BPH remains controversial. We aimed to employ a network meta-analysis to compare and assess differences among commonly used and recommended poly-herbal TCM formulations outlined in the Chinese guidelines for BPH treatment, providing clinical medication recommendations and guidance. Methods: We extensively searched for RCTs of BPH patients that had oral poly-herbal TCM formulations and WM treatment, covering both English and Chinese databases up to 31 October 2023. The quality of the included studies was evaluated using the Cochrane risk-of-bias tool Version 2 (ROB2). A Bayesian network meta-analysis was performed to assess the effectiveness of various formulations, followed by sensitivity and subgroup analyses. Results: Our meta-analysis included 107 RCTs involving 11,037 patients across 16 oral poly-herbal TCM formulations. The quality of the selected studies was assessed as "Some concerns". Most formulations combined with WM demonstrated superior therapeutic efficacy compared to WM alone. For clinical effective rate, Jingui Shenqi pill (JGSQ) + WM had the highest-ranking probability (87.38%). Concerning International Prostate Symptom Score (IPSS) and maximum flow rate of urine, Guizhi Fuling capsule (GZFL) + WM was most effective (91.10% and 98.55%). Regarding the quality of life score and postvoid residual urine, Pulean tablet (PLA) + WM ranked first (86.71% and 91.81%). In controlling prostate volume, Huange capsule (HE) + WM demonstrated the highest efficacy (95.65%). Additionally, among the interventions, Lingze (LZ) + WM capsule exhibited the lowest incidence of adverse drug reactions (2.32%). Conclusion: Combining oral poly-herbal TCM formulations with WM may provide greater therapeutic benefits in BPH treatment compared to WM alone. JGSQ, GZFL, PLA, and HE emerged as promising treatment options. However, further rigorous empirical studies are essential to substantiate these findings. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=459651, CRD 42023459651.

Associations Between Serum Estrogen Levels and Urinary Incontinence in Women: A Cross-sectional Analysis of NHANES 2013 to 2016.

OBJECTIVE: To explore the relationship between serum estrogen levels and urinary incontinence in a nationally representative female population. MATERIALS AND METHODS: We included women who had serum estradiol measurements and self-reported urinary incontinence problems in the 2013-2016 National Health and Nutrition Examination Survey cycles. A weighted multivariable logistic regression model was used to determine the association between urinary incontinence and serum estrogen levels after adjusting for age, race, Body Mass Index, diabetes, venipuncture, hypertension, poverty-to-income ratio, smoking, marital status, alcohol use, education, and menopause. RESULT: A total of 4114 individuals were ultimately included in our study. Of these women, 1200 (29.17%) complained of urge urinary incontinence (UUI), 1674 (40.69%) complained of stress urinary incontinence (SUI), 730 (17.74%) complained of mixed urinary incontinence (MUI). Women in the lowest quartile of serum estrogen were more likely to complain of UUI compared to those in the highest quartile (OR=1.885; 95% CI=1.042-3.412, P = .039). No association was noted between serum estrogen levels and SUI or MUI. CONCLUSION: Our study shows a significant association between low serum estrogen level and the increased likelihood of UUI in women. Further research is required to validate our findings, elucidate the physiological mechanisms that underlie them, and assess potential therapeutic implications.