Clinical features and influencing factors of adolescent major depressive disorder with suicidal and self-injurious behaviour.

OBJECTIVE: To analyse the related influencing factors of adolescent major depressive disorder (MDD) with suicidal and self-injurious behaviour (SSIB). METHODS: A total of 299 adolescents with MDD who were admitted to the psychiatric department of the hospital between February 2022 and July 2023 were selected using the convenience sampling method. The participants were divided into the SSIB group (n = 110) and the non-SSIB group (n = 189) according to whether SSIB was present, and related indicators were collected and compared. RESULTS: The patients' ages at the time of their first SSIB ranged from 10 to 18 years old, with a mean age of 13.30 ± 1.74 years. The most commonly injured parts were the lower arm and wrist (42.13%), and the most common injury was cutting, accounting for 40.00% of the total patients. The most common type of self-injury differed by sex (X2 = 17.798, P = 0.006); for men, hitting was the most common, and for women, cutting was the most common. In 51.41% of the patients, the period between the initial thought and the actual committing of the SSIB was less than 5 minutes. The scores of the Eysenck Personality Questionnaire, the Barratt Impulsivity Scale, the Buss-Perry Aggression Questionnaire, the Symptom Checklist-90 (all P < 0.001), and the health-risk behaviour scale (67.47 ± 12.59 vs. 41.58 ± 11.36, t = 9.587, P < 0.001) were significantly increased in the SSIB group compared with the non-SSIB group. In addition, the total score of quality of life (QOL) (11.36 ± 4.32 vs. 16.43 ± 5.64, t = 5.496, P < 0.001) was decreased in the SSIB group compared with the non-SSIB group. CONCLUSION: The SSIB of adolescent patients with MDD is related to various factors, including impulsiveness, aggressiveness, personality traits, QOL, and mental health level.

Effect of Population Density on Personality of Crayfish (Procambarus clarkii).

Personality is widely observed in animals and has important ecological and evolutionary implications. In addition to being heritable, personality traits are also influenced by the environment. Population density commonly affects animal behavior, but the way in which it shapes animal personality remains largely unknown. In this study, we reared juvenile crayfish at different population densities and measured their personality traits (shyness, exploration, and aggression) after reaching sexual maturity. Our results showed repeatability for each behavior in all treatments, except for the shyness of females at medium density. There was a negative correlation between shyness and exploration in each treatment, and aggression and exploration were positively correlated in medium- and high-density females. These indicate the presence of a behavior syndrome. On average, the crayfish raised at higher population densities were less shy, more exploratory, and more aggressive. We found no behavioral differences between the sexes in crayfish. These results suggested that population density may affect the average values of behavioral traits rather than the occurrence of personality traits. Our study highlights the importance of considering population density as a factor influencing personality traits in animals and, therefore, might help us to understand animal personality development.

HE4-based nomogram for predicting overall survival in patients with idiopathic pulmonary fibrosis: construction and validation.

Idiopathic pulmonary fibrosis (IPF) is a life-threatening interstitial lung disease. Identifying biomarkers for early diagnosis is of great clinical importance. The epididymis protein 4 (HE4) is important in the process of inflammation and fibrosis in the epididymis. Its prognostic value in IPF, however, has not been studied. The mRNA and protein levels of HE4 were used to determine the prognostic value in different patient cohorts. In this study, prognostic nomograms were generated based on the results of the cox regression analysis. We identified the HE4 protein level increased in IPF patients, but not the HE4 gene expression. The increased expression of HE4 correlated positively with a poor prognosis for patients with IPF. The HR and 95% CI were 2.62 (1.61-4.24) (p < 0.001) in the training set. We constructed a model based on the risk-score = 0.16222182 * HE4 + 0/0.37580659/1.05003609 (for GAP index 0-3/4-5/6-8) + (- 1.1183375). In both training and validation sets, high-risk patients had poor prognoses (HR: 3.49, 95%CI 2.10-5.80, p = 0.001) and higher likelihood of dying (HR: 6.00, 95%CI 2.04-17.67, p = 0.001). Analyses of calibration curves and decision curves suggest that the method is effective in predicting outcomes. Furthermore, a similar formulation was used in a protein-based model based on HE4 that also showed prognostic value when applied to IPF patients. Accordingly, HE4 is an independent poor prognosis factor, and it has the potential to predict IPF patient survival.

Pretreatment mortality risk prediction model in patients with polymyositis/dermatomyositis-associated interstitial lung disease.

OBJECTIVES: Risk prediction for patients with polymyositis/dermatomyositis-associated interstitial lung disease (PM/DM-ILD) is challenging due to heterogeneity in the disease course. We aimed to develop a mortality risk prediction model for PM/DM-ILD. METHODS: This prognostic study analysed patients with PM/DM-ILD admitted to Nanjing Drum Hospital from 2016 to 2021. The primary outcome was mortality within 1 year. We used a least absolute shrinkage and selection operator (LASSO) logistic regression model to identify predictive laboratory indicators. These indicators were used to create a laboratory risk score, and we developed a mortality risk prediction model by incorporating clinical factors. The evaluation of model performance encompassed discrimination, calibration, clinical utility and practical application for risk prediction and prognosis. RESULTS: Overall, 418 patients with PM/DM-ILD were enrolled and randomly divided into development (n=282) and validation (n=136) cohorts. LASSO logistic regression identified four optimal features in the development cohort, forming a laboratory risk score: C reactive protein, lactate dehydrogenase, CD3+CD4+ T cell counts and PO2/FiO2. The final prediction model integrated age, arthralgia, anti-melanoma differentiation-associated gene 5 antibody status, high-resolution CT pattern and the laboratory risk score. The prediction model exhibited robust discrimination (area under the receiver operating characteristic: 0.869, 95% CI 0.811 to 0.910), excellent calibration and valuable clinical utility. Patients were categorised into three risk groups with distinct mortality rates. The internal validation, sensitivity analyses and comparative assessments against previous models further confirmed the robustness of the prediction model. CONCLUSIONS: We developed and validated an evidence-based mortality risk prediction model with simple, readily accessible clinical variables in patients with PM/DM-ILD, which may inform clinical decision-making.

Factors affecting the use of artificial intelligence generated content by subject librarians: A qualitative study.

To explore the factors affecting the use of artificial intelligence generated content (AIGC) by subject librarians through understanding their perceptions of AIGC. Interpretive phenomenological analysis (IPA) and technology acceptance model (TAM) were used in semi-structured interviews to explore the external variables of perceived ease of use and perceived usability of AIGC application in subject librarians. The perceptions of subject librarians towards AIGC included performance, risk perceptions, ability enhancement, and affective attitude. Attentions were paid to AIGC's performances in providing customized services, optimizing collection resources and improving cost efficiency. The risk perception involved technical stability, data security, user acceptance and occupational risk, the ability enhancement involved the improvement of personal literacy, innovative ability, and self-confidence through the use of AIGC technology, and the affective attitudes included not only excitement and anticipation for the technical potential of AIGC, but also concerns and skepticism about it, and critical attitudes toward its application in academic settings and the ethical issues it may raise. TAM analysis on the factors affecting the use of AIGC by subject librarians indicates that the external influencing factors of perceived ease of use include personal literacy, innovative ability, self-confidence enhancement and affective attitude; the external influencing factors of perceived usability include precise service, collection resource optimization, cost-effectiveness, technological risk, user acceptance and occupational risk. These factors constitute a theoretical framework for understanding and promoting the acceptance and effective use of AIGC by subject librarians. TAM analysis combined with IPA exploration on the external variables of perceived ease of use and perceived usability of AIGC application can identify the key factors affecting subject librarians' perceptions of AIGC, propose strategies for optimizing librarians' roles, enhancing information recognition ability and privacy protection, thus providing guidance for effective use of AIGC in library.

A deep learning-based 3D Prompt-nnUnet model for automatic segmentation in brachytherapy of postoperative endometrial carcinoma.

PURPOSE: To create and evaluate a three-dimensional (3D) Prompt-nnUnet module that utilizes the prompts-based model combined with 3D nnUnet for producing the rapid and consistent autosegmentation of high-risk clinical target volume (HR CTV) and organ at risk (OAR) in high-dose-rate brachytherapy (HDR BT) for patients with postoperative endometrial carcinoma (EC). METHODS AND MATERIALS: On two experimental batches, a total of 321 computed tomography (CT) scans were obtained for HR CTV segmentation from 321 patients with EC, and 125 CT scans for OARs segmentation from 125 patients. The numbers of training/validation/test were 257/32/32 and 87/13/25 for HR CTV and OARs respectively. A novel comparison of the deep learning neural network 3D Prompt-nnUnet and 3D nnUnet was applied for HR CTV and OARs segmentation. Three-fold cross validation and several quantitative metrics were employed, including Dice similarity coefficient (DSC), Hausdorff distance (HD), 95th percentile of Hausdorff distance (HD95%), and intersection over union (IoU). RESULTS: The Prompt-nnUnet included two forms of parameters Predict-Prompt (PP) and Label-Prompt (LP), with the LP performing most similarly to the experienced radiation oncologist and outperforming the less experienced ones. During the testing phase, the mean DSC values for the LP were 0.96 ± 0.02, 0.91 ± 0.02, and 0.83 ± 0.07 for HR CTV, rectum and urethra, respectively. The mean HD values (mm) were 2.73 ± 0.95, 8.18 ± 4.84, and 2.11 ± 0.50, respectively. The mean HD95% values (mm) were 1.66 ± 1.11, 3.07 ± 0.94, and 1.35 ± 0.55, respectively. The mean IoUs were 0.92 ± 0.04, 0.84 ± 0.03, and 0.71 ± 0.09, respectively. A delineation time < 2.35 s per structure in the new model was observed, which was available to save clinician time. CONCLUSION: The Prompt-nnUnet architecture, particularly the LP, was highly consistent with ground truth (GT) in HR CTV or OAR autosegmentation, reducing interobserver variability and shortening treatment time.

Epidemiology and risk factors of oral frailty among older people: an observational study from China.

OBJECTIVES: This study aimed to compare the prevalence of oral frailty among community-dwelling older people in Nanjing, China with the usage of different measurements, and to investigate the potential risk factors of oral frailty. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: A total of 338 community-dwelling older people in Nanjing, China were recruited. METHODS: Oral frailty was measured based on the Oral Frailty Index-8 (OFI-8) scale and other measurement methods including the number of natural teeth (TN), repetitive saliva-swallowing test (RSST), and oral diadochokinesis (ODK). The chi-square test and the binary logistic regression analysis were performed to identify potential risk factors for oral frailty. RESULTS: There were 310 participants included in the analysis. Prevalence of oral frailty by using the OFI-8, OFI-8 + TN, OFI-8 + ODK, OFI-8 + TN + ODK and RSST measurement methods were 69.0%, 27.4%, 51.9%, 21.0% and 2.9%, respectively. Passive smoking (OR = 2.04; 95%CI 1.03-4.03), being widowed/unmarried (OR1 = 2.53; 95%CI 1.25-5.10; OR2 = 2.94; 95%CI 1.12-7.77), pre-frailty (OR = 1.76; 95%CI 1.03-3.01), frailty (OR = 3.01; 95%CI 1.39-6.54), and aged 80 years and above (OR = 3.99; 95%CI 1.35-11.81) were found to be risk factors of oral frailty by the usage of the four kinds of measurement methods. CONCLUSIONS AND IMPLICATIONS: The definition and diagnostic criteria of oral frailty are strongly needed to be unified in future research. Only subjective assessment is not enough for assessing oral frailty. Among objective indicators, RSST is not suitable as a screening method for oral frailty. In addition, objective indicators including TN and ODK should be valued for early screening and preventive interventions. The risk factors of oral frailty include physical frailty, passive smoking, and being widowed.

In-situ fabrication of Cr doped FeNi LDH on commercial stainless steel for oxygen evolution reaction.

Commercial stainless steel has attracted increasing interest due to their rich content in transition metal elements and corrosion resistance properties. In this work, we design a facile and rapid route to in-situ fabricate the Cr doped FeNi layered double hydroxides nanosheets (LDHs) on modified stainless steel (Cr-FeNi LDH @ ESS) under ambient condition.The ultra small scaled 2D structure only around 20 nm diameter and metal ions with multivalent oxidation state were observed on the in situ fabricated LDHs, which provides high active area and active sites and thus promote excellent oxygen evolution reaction (OER). The Cr-FeNi LDH @ESS electrocatalysts exhibit an over potential of 280 mV at 10 mA cm-2 and achieves a Tafel slope of 44 mV dec-1 for OER in the 1.0 M KOH aqueous solution. We anticipate that the operating strategy of our system may promote the development of commercial non-precious productions as the efficient electrocatalysts for energy storage and conversion.

Psychometric evaluation of the student nurse stressor-14 scale for undergraduate nursing interns.

BACKGROUND: Currently, there are few scales used to assess the stressors experienced by undergraduate nursing interns during clinical practice, and the assessment of stressors during clinical practice is not comprehensive; the scale includes some unique stressors during training that is not available in the existing instruments used to assess nursing student practice stress in China. AIM: The study aimed to explore the structure of the Chinese revision of the Student Nurse Stressor-14 Scale(SNS-14-CHI)and investigate the psychometric properties it among Chinese undergraduate nursing interns. METHODS: The original scale was culturally adjusted and revised after expert correspondence on the entries, and 414 undergraduate nursing interns were recruited from three cities in China to administer the questionnaire. Reliability was measured by internal consistency, fold-half reliability, and stability. Content validity was evaluated using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) to assess the validity of the SNS-14-CHI. RESULTS: The SNS-14-CHI retained 14 items, the EFA supported a 2-factor structure, and the items' factor attribution differed from the original scale. The CFA results showed a good model fit. The Cronbach coefficient of the scale was 0.934, and the coefficient values of the two factors were 0.890 and 0.898. The content validity index of the scale was 0.964.The cumulative variance contribution of the 2-factor structure was 60.445%. The split-half reliability and stability were 0.869,0.762, respectively. CONCLUSION: The SNS-14-CHI has excellent reliability and validity among undergraduate nursing trainees. The evaluation results of the scale can provide a reference for nursing managers to develop educational programs and interventions to quantify nursing student stress.

Mechanosensitive accumulation of non-muscle myosin IIB during mitosis requires its translocation activity.

Non-muscle myosin II (NMII) is a force-generating mechanosensitive enzyme that responds to mechanical forces. NMIIs mechanoaccumulate at the cell cortex in response to mechanical forces. It is essential for cells to mechanically adapt to the physical environment, failure of which results in mitotic defects when dividing in confined environment. Much less is known about how NMII mechanoaccumulation is regulated during mitosis. We show that mitotic cells respond to compressive stress by promoting accumulation of active RhoA at the cell cortex as in interphase cells. RhoA mechanoresponse during mitosis activates and stabilizes NMIIB via ROCK signaling, leading to NMIIB mechanoaccumulation at the cell cortex. Using disease-related myosin II mutations, we found that NMIIB mechanoaccumulation requires its motor activity that translocates actin filaments, but not just its actin-binding function. Thus, the motor activity coordinates structural movement and nucleotide state changes to fine-tune actin-binding affinity optimal for NMIIs to generate and respond to forces.

Clinical significance of interleukin-6, total bilirubin, CD3 + CD4 + T cells counts in the acute exacerbation of connective tissue disease-associated interstitial lung disease: a cross-sectional study.

OBJECTIVE: Interstitial lung disease (ILD) is a severe complication of connective tissue disease (CTD) that can significantly impact patients' prognosis and quality of life. However, the current diagnostic arena lacks reliable biomarkers for detecting and monitoring the progression and exacerbation of CTD-ILD. This study aimed to investigate the clinical value of 12 serum cytokines in the diagnosis of CTD-ILD and prediction of the risk of acute exacerbation (AE) in this disease. METHODS: This study was a cross-sectional investigation. Ninety-one hospitalized CTD patients were allocated into two groups: CTD-ILD group (n = 61) and CTD-non-ILD group (n = 30), and 30 sex-age matched healthy volunteers were enrolled as controls. The serum concentrations of interferon (IFN)-α, IFN-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, and IL-1ß were measured by Luminex suspension arrays. Logistic regression was employed to determine the significance of variables in the occurrence of AE-CTD-ILD. A nomogram was constructed to visualize the independent variables. RESULTS: Elevated levels of IL-6, IL-8, and TNF-α were observed and compared in the CTD-ILD group with CTD-non-ILD (all P < 0.05). Similarly, the levels of IL-6, IL-8 and TNF-α were higher in the acute exacerbation (AE-CTD-ILD) group compared with stable CTD-ILD (S-CTD-ILD) (P < 0.001, P < 0.001, and P = 0.022). Significant correlations between serum IL-6 and PaO2/FiO2 ratio (r = - 0.463, P < 0.001), percent predicted forced vital capacity (FVC%; r = - 0.362, P < 0.05), and total ground-glass opacity (GGO) score (r = 0.439, P < 0.001) were observed in CTD-ILD patients. Multivariate logistic regression analysis revealed that elevated IL-6 levels, total bilirubin (TBil), and decreased CD3 + CD4 + T cells counts were independent risk factors for the occurrence of AE-CTD-ILD (OR = 1.121, P = 0.024; OR = 1.865, P = 0.047; OR = 0.983, P = 0.037, respectively). Furthermore, by employing these three variables in combination for the prediction of AE status, their collective impact surpasses the independent effects of any single biomarker. CONCLUSIONS: Elevated levels of serum IL-6, IL-8, and TNF-α were associated with the complication of ILD in CTD patients and the occurrence of AE in CTD-ILD patients. IL-6 could be a promising serum biomarker of severity and the occurrence of AE in CTD-ILD patients. The combination of the three variables (IL-6 level, TBil and CD3 + CD4 + T cells) predicted the AE-CTD-ILD better.

Evaluation of the genotype I Japanese encephalitis virus as a stable viral vector for foreign gene expression.

Manipulation of the flavivirus genome to accommodate and express a heterologous gene of interest has become an attractive approach for gene delivery and the development of viral-vectored vaccines. However, due to the inherent genetic instability of the flavivirus genomes, the construction of recombinant viruses carrying a foreign gene could be problematic and heavily resistant. In this study, the possibility of the Japanese encephalitis virus (JEV) as a stable flavivirus vector for the expression of a foreign gene was assessed using reverse genetics. The full-length cDNA genome of genotype I (GI) JEV inherently possessed excellent stability and manipulability in a bacterial host, while mutations and deletions accumulated in the cDNA genomes of genotype Ⅲ (GⅢ) JEV strains. Using the GI JEV as backbones, we generate a panel of recombinant viruses expressing various foreign genes. All recombinant viruses exhibited excellent genetic stability and efficiently express foreign genes for at least ten serial passages in vitro. In application, a convenient, rapid and reliable image-based assay for neutralizing antibody testing and antiviral drug discovery was established with a mCherry-reporter recombinant virus (rBJ-mCherry). Meanwhile, the recombinant viruses expressing the antigens of the African swine fever virus (ASFV) or Classical swine fever virus (CSFV) could effectively induce antibody responses to the JEV vector and foreign antigens in a mouse vaccination model. Therefore, GI JEV strains could serve as viral vectors accommodating the expression of large foreign genes.

N6-methyladenosine methylation mediates non-coding RNAs modification in microplastic-induced cardiac injury.

Owing to their potential adverse health effects, global contamination by microplastics (MPs) has attracted increased scientific and societal concerns. However, in vivo studies on MP toxicity, along with its effects and underlying mechanisms, remain limited. We recently found that non-coding RNA (ncRNAs) contribute to MP-mediated vascular toxicity. Moreover, previous studies have identified N6-methyladenosine (m6A) modifications in ncRNAs as influencing factors in cardiovascular disease. However, whether and how m6A modifications in ncRNAs are affected by MP-induced cardiotoxicity remain unknown. Herein, we profiled differentially expressed ncRNAs and their related m6A modification profiles in MP-exposed myocardial tissue using RNA sequencing (RNA-seq) and methylated RNA immunoprecipitation sequencing (MeRIP-seq). First, we observed that MPs accumulated in different organs and upregulated apoptosis in the heart, liver, spleen, and kidney cells. Furthermore, total m6A and METTL3 levels increased in the myocardium after exposure to MPs. RNA-seq results revealed that 392 lncRNAs and 302 circRNAs were differentially expressed in MP-treated mouse myocardium compared to the control group. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed that these altered lncRNAs and circRNAs were closely associated with endocytosis, cellular senescence, and cell cycle signaling pathways, which may cause cardiotoxicity. Furthermore, MeRIP-seq data showed different distributions and abundances of m6A modifications in lncRNAs and circRNAs. Additionally, we identified differentially m6A methylated lncRNAs and circRNAs through conjoint analysis of the two high-throughput sequencing datasets and found that both m6A modifications and the expression of circ-Arfgef2 and lncG3bp2 were upregulated after exposure to MPs. This suggests that MP-induced m6A modifications in ncRNAs are involved in cardiotoxicity. Our findings contribute to a better understanding of MP-induced cardiotoxicity and new molecular targets for treating cardiac injury.

Inhibition of phosphoinositide­3 kinases γ/δ ameliorates pulmonary granuloma by rescuing Treg function in a sarcoidosis model.

Sarcoidosis is a multisystem inflammatory disease characterized by the development of Th1/Th17/regulatory T cells (Tregs)-related non-caseating granulomas. Phosphoinositide-3 kinases δ/γ (PI3Kδ/γ) play an important role in the maintenance of effective immunity, especially for Tregs homeostasis and stability. In the present study, superoxide dismutase A (SodA) stimulation was used to establish the sarcoidosis mouse model. The second immune stimulus was accompanied by CAL-101 (PI3Kδ inhibitor) or AS-605240 (PI3Kδ/γ inhibitor) treatment. To detect the effect of the PI3Kδ/γ inhibitor on the morphology of pulmonary granuloma and the activation of the PI3K signaling pathway, hematoxylin and eosin staining and immunofluorescence and western blotting was used, respectively. Fluorescence-activated cell sorting analysis and reverse transcription-quantitative PCR were adopted to detect the effect of the PI3Kδ/γ inhibitor on the SodA-induced sarcoidosis mouse model in respect to immune cell disorder and the function of Treg cells, with CD4+CD25- T cells and CD4+CD25+ T cells sorted by magnetic cell sorting. The results demonstrated that the inhibition of PI3Kδ/γ by transtracheal CAL-101/AS-605240 administration facilitated pulmonary granuloma formation. These therapeutic effects were associated with certain mechanisms, including suppressing the aberrantly activated PI3K/Akt signaling in both pulmonary granuloma and Tregs, particularly rescuing the suppressive function of Tregs. Notably, CAL-101 was more effective in immune modulation compared with AS-605240 and could overcome the aberrantly activated Akt in the lung and Tregs. These results suggest that PI3K/Akt signaling, especially the PI3Kδ subunit, can play a key role in optimal Tregs-mediated protection against pulmonary sarcoidosis. Therefore, transtracheal usage of PI3Kδ/γ inhibitors is an attractive therapy that may be developed into a new immune-therapeutic principle for sarcoidosis in the future.

Allicin Inhibits Porcine Reproductive and Respiratory Syndrome Virus Infection In Vitro and Alleviates Inflammatory Responses.

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically important pathogens to the swine industry worldwide over the past three decades. No approved effective antiviral drug is available to control this virus. The antiviral effects of allicin (diallyl thiosulfinate) on many human and animal viruses have been documented. However, the antiviral effect of allicin on PRRSV infection remains unknown. In this study, we found that allicin exhibited an inhibitory effect on HP-PRRSV and NADC30-like PRRSV in a dose-dependent manner by interfering with viral entry, replication, and assembly. Furthermore, allicin alleviated the expression of pro-inflammatory cytokines (IFN-ß, IL-6, and TNFα) induced by PRRSV infection. The pro-inflammatory signaling pathways, TNF signaling pathway and MAPK signaling pathway, up-regulated by PRRSV infection were restored by allicin treatment. Taken together, these results demonstrate that allicin has antiviral activity against PRRSV and ameliorates inflammatory responses induced by PRRSV infection, suggesting that allicin is a promising drug candidate for anti-PRRSV therapy in vivo.

Systematic analysis of the prognostic and immunological role of DHX33 in pan-cancer.

DEAH-box helicase 33 (DHX33) is a potent oncogenic agent on patients with hepatocellular carcinoma and colon cancer. Nevertheless, the prognostic significance of DHX33 in human pan-cancers remains unclear. Various bioinformatics tools have been used to clarify the oncogenic effects of DHX33 in pan-cancers. The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) were used to evaluate DHX33 at the mRNA and protein levels, respectively. The pan-cancer prognostic prediction value of DHX33 was evaluated using the Kaplan-Meier plotter. The association between DHX33 levels and clinicopathological features was then determined using the UALCAN database. In addition, gene set enrichment analysis and nomogram prediction models were constructed. The association between DHX33 levels and immune cell infiltration was then assessed using TISIDB. We determined that DHX33 is aberrantly overexpressed in pan-cancers and related to lung adenocarcinoma (LUAD) clinical stage (p < .001). Moreover, DHX33 overexpression was indicative of poor overall survival, disease-free survival, and progression-free interval in patients with LUAD (p < .05). Furthermore, DHX33 levels were associated with age, N stage, T stage, and pathologic stage in patients with LUAD (p < .001). Additionally, multivariate Cox analysis revealed that DHX33 was an independent risk factor for OS in patients with LUAD. A nomogram model between DHX33 levels and characteristic clinical parameters was developed. Additionally, DHX33 levels correlated with immunomodulators and chemokines. Finally, gene set enrichment analysis revealed that the amyloid fiber formation pathway and the WICH complex positively regulates RNA expression pathway, which was the most enriched in LUAD. Our data revealed oncogenic effects of DHX33 in various cancers. We suggest that DHX33 may serve as a biomarker for poor prognosis in LUAD.

Photoelectrochemical N2 -to-NH3 Fixation with High Efficiency and Rates via Optimized Si-Based System at Positive Potential versus Li0/.

As a widely used commodity chemical, ammonia is critical for producing nitrogen-containing fertilizers and serving as the promising zero-carbon energy carrier. Photoelectrochemical nitrogen reduction reaction (PEC NRR) can provide a solar-powered green and sustainable route for synthesis of ammonia (NH3 ). Herein, an optimum PEC system is reported with an Si-based hierarchically-structured PdCu/TiO2 /Si photocathode and well-thought-out trifluoroethanol as the proton source for lithium-mediated PEC NRR, achieving a record high NH3 yield of 43.09 µg cm-2 h-1 and an excellent faradaic efficiency of 46.15% under 0.12 MPa O2 and 3.88 MPa N2 at 0.07 V versus lithium(0/+) redox couple (vs Li0/+ ). PEC measurements coupled with operando characterization reveal that the PdCu/TiO2 /Si photocathode under N2 pressures facilitate the reduction of N2 to form lithium nitride (Li3 N), which reacts with active protons to produce NH3 while releasing the Li+ to reinitiate the cycle of the PEC NRR. The Li-mediated PEC NRR process is further enhanced by introducing small amount of O2 or CO2 under pressure by accelerating the decomposition of Li3 N. For the first time, this work provides mechanistic understanding of the lithium-mediated PEC NRR process and opens new avenues for efficient solar-powered green conversion of N2 -to-NH3 .

Beyond bacteria: Reconstructing microorganism connections and deciphering the predicted mutualisms in mammalian gut metagenomes.

Numerous gut microbial studies have focused on bacteria. However, archaea, viruses, fungi, protists, and nematodes are also regular residents of the gut ecosystem. Little is known about the composition and potential interactions among these six kingdoms in the same samples. Here, we unraveled the complex connection among them using approximately 123 gut metagenomes from 42 mammalian species (including carnivores, omnivores, and herbivores). We observed high variation in bacterial and fungal families and relatively low variation in archaea, viruses, protists, and nematodes. We found that some fungi in the mammalian intestine might come from environmental sources (e.g., soil and dietary plants), and some might be native to the intestine (e.g., the occurrence of Neocallimastigomycetes). The Methanobacteriaceae and Plasmodiidae families (archaea and protozoa, respectively) were predominant in these metagenomes, whereas Onchocercidae and Trichuridae were the two most common nematodes, and Siphoviridae and Myoviridae the two most common virus families in these mammalian gut metagenomes. Interestingly, most of the pairwise co-occurrence patterns were significantly positive among these six kingdoms, and significantly negative networks mainly occurred between fungi and prokaryotes (both bacteria and archaea). Our study revealed some inconvenient characteristics in the mammalian gut microorganism ecosystem: (1) the community formed by members of the analyzed kingdoms reflects the life history of the host and the potential threat posed by pathogenic protists and nematodes in mammals; and (2) the networks suggest the existence of predicted mutualism among members of these six kingdoms and of the predicted competition, mainly among fungi and other kingdoms.

Unique DUOX2+ACE2+ small cholangiocytes are pathogenic targets for primary biliary cholangitis.

Cholangiocytes play a crucial role in bile formation. Cholangiocyte injury causes cholestasis, including primary biliary cholangitis (PBC). However, the etiology of PBC remains unclear despite being characterized as an autoimmune disease. Using single-cell RNA sequencing (scRNA-seq), fluorescence-activated-cell-sorting, multiplex immunofluorescence (IF) and RNAscope analyses, we identified unique DUOX2+ACE2+ small cholangiocytes in human and mouse livers. Their selective decrease in PBC patients was associated with the severity of disease. Moreover, proteomics, scRNA-seq, and qPCR analyses indicated that polymeric immunoglobulin receptor (pIgR) was highly expressed in DUOX2+ACE2+ cholangiocytes. Serum anti-pIgR autoantibody levels were significantly increased in PBC patients, regardless of positive and negative AMA-M2. Spatial transcriptomics and multiplex IF revealed that CD27+ memory B and plasma cells accumulated in the hepatic portal tracts of PBC patients. Collectively, DUOX2+ACE2+ small cholangiocytes are pathogenic targets in PBC, and preservation of DUOX2+ACE2+ cholangiocytes and targeting anti-pIgR autoantibodies may be valuable strategies for therapeutic interventions in PBC.