DDX58 variant triggers IFN-ß-induced autophagy in trabecular meshwork and influences intraocular pressure.

Singleton-Merten syndrome (SMS) is a rare immunogenetic disorder affecting multiple systems, characterized by dental dysplasia, aortic calcification, glaucoma, skeletal abnormalities, and psoriasis. Glaucoma, a key feature of both classical and atypical SMS, remains poorly understood in terms of its molecular mechanism caused by DDX58 mutation. This study presented a novel DDX58 variant (c.1649A>C [p.Asp550Ala]) in a family with childhood glaucoma. Functional analysis showed that DDX58 variant caused an increase in IFN-stimulated gene expression and high IFN-ß-based type-I IFN. As the trabecular meshwork (TM) is responsible for controlling intraocular pressure (IOP), we examine the effect of IFN-ß on TM cells. Our study is the first to demonstrate that IFN-ß significantly reduced TM cell viability and function by activating autophagy. In addition, anterior chamber injection of IFN-ß remarkably increased IOP level in mice, which can be attenuated by treatments with autophagy inhibitor chloroquine. To uncover the specific mechanism underlying IFN-ß-induced autophagy in TM cells, we performed microarray analysis in IFN-ß-treated and DDX58 p.Asp550Ala TM cells. It showed that RSAD2 is necessary for IFN-ß-induced autophagy. Knockdown of RSAD2 by siRNA significantly decreased autophagy flux induced by IFN-ß. Our findings suggest that DDX58 mutation leads to the overproduction of IFN-ß, which elevates IOP by modulating autophagy through RSAD2 in TM cells.

Micropulse laser trabeculoplasty on Chinese patients with glaucoma or ocular hypertension: average 35 months follow-up results.

BACKGROUND: Glaucoma is a group of eye diseases that can damage the optic nerve and cause vision loss. A novel technology micropulse laser trabeculoplasty (MLT) can use duty-circle subvisible laser pulses to treat glaucoma. The aim of this study is to evaluate the efficacy of 360° MLT to alleviate intraocular pressure (IOP) in patients with glaucoma. METHODS: This was a single-center prospective study on patients treated with 360° MLT using a Diode True-Yellow 577-nm Laser with MicroPulse technology. All the patients were recruited from the Department of Ophthalmology. Follow-up visits were carried out at 1 day, 1 week, 1 month, 3 months, 6 months, 18 months, and 36 months after the procedure. Best-corrected visual acuity (BCVA), Intraocular pressure (IOP), and vertical cup-to-disc ratio (C/D ratio) were measured during the follow-up. Repeated-measures analysis of variance (ANOVA) and Kaplan-Meier analysis were performed to evaluate the outcomes. RESULTS: A total of 39 eyes from 25 patients were included in this study (10 men/15 women). The average age of patients was 41.47 ± 14.39 years old, and the baseline IOP was 21.13 ± 7.75 mmHg. MLT significantly reduced the IOP at 1 day (range 15.61-19.01, P = 0.0218), 3 months (range 16.47-19.22, P = 0.0390), and 6 months (range 15.38-18.56, P = 0.0332) compared with the baseline. However, by the end of the study, only 21.88% of patients demonstrated a ≥ 20% IOP reduction, while seven eyes needed further laser or surgical treatment. The IOP of glaucoma patients was significantly lower than the ocular hypertension patients at 1 month (P = 0.0124), 3 months (P = 0.0004), 18 months (P = 0.0061) and 36 months (P = 0.0119). CONCLUSIONS: Micropulse laser trabeculoplasty reduce IOP in patients with glaucoma or ocular hypertension for a short period, but its lowering efficiency is limited up to 6 months of the follow-up period.

Socioeconomic disadvantages and vulnerability to the pandemic among children and youth: A macro-level investigation of American counties.

This study intends to reveal the underlying structural inequity in vulnerability to infection of the novel coronavirus disease pandemic among children and youth. Using multi-source data from New York Times novel coronavirus disease tracking project and County Health Rankings & Roadmap Program, this study shows that children and youth in socioeconomically disadvantaged status are faced with disproportionate risk of infection in this pandemic. On the county level, socioeconomic disadvantages (i.e., single parent family, low birthweight, severe housing problems) contribute to the confirmed cases and death cases of the novel coronavirus disease. Policymakers should pay more attention to this vulnerable group to implement more targeted and effective epidemic prevention and control.

Why some donors are more willing to donate platelets? ----a qualitative study on 25 regular platelet donors in Guangzhou, China.

BACKGROUND: Since 1998, China has gradually moved toward voluntary uncompensated blood donation. In some cities, the shortage of platelets has been noticeably severe. Mutual assistance that collects blood from one's family and social networks is a potential solution. The measure, however, turned out problematic. There are donors who choose to donate platelets over whole blood without compensations, and donate platelets directly to blood banks instead of via the mutual assistance system. This study explores reasons behind their choices qualitatively. METHODS: This report is based on data conducted from January to February 2018; 25 uncompensated regular platelet donors were interviewed. The blood component donation service team in Guangzhou facilitated the data collection process and referred prospectively eligible blood donors to our research team. The interviews took about 30 min to two hours to complete. The qualitative data were analyzed by using the software ATLAS.ti 8. RESULTS: Platelet donation takes a much long time than whole blood donation and requires complicated processes. It may also cause discomfort as the other blood components are returned to the body, causing physical and psychological distress due to worries about contamination. Thus, platelet donation tends to involve higher time and psychological costs than whole blood donation. Yet, it has short collection intervals that allows for more frequent donations, and urgency of a severer shortage than whole blood. Hence, regular platelet donors may feel higher significance in platelet donation than whole blood donation, with the belief that more lives would be saved. Some whole blood donors thus switched to become platelet donors. Mutual assistance blood donation was not chosen by the participants for platelet donation, because such donations may exert moral pressure to both the donors and recipients. Furthermore, "acquaintance" has been loosely defined; the system has sometimes been manipulated to become profit-making monetary transactions. It hence failed. CONCLUSIONS: The practice of platelet donation reinforces the understanding that blood donation is a gift giving process performed among strangers. A safe and sustainable voluntary blood supply can only be secured in the absence of monetary transactions and moral pressure.

Effects of polystyrene microplastic composite with florfenicol on photosynthetic carbon assimilation of rice (Oryza sativa L.) seedlings: Light reactions, carbon reactions, and molecular metabolism.

The effects of co-exposure to antibiotics and microplastics in agricultural systems are still unclear. This study investigated the effects of florfenicol (FF) and polystyrene microplastics (PS-MPs) on photosynthetic carbon assimilation in rice seedlings. Both FF and PS-MPs inhibited photosynthesis, while PS-MPs can alleviate the toxicity of FF. Chlorophyll synthesis genes (HEMA, HEMG, CHLD, CHLG, CHLM, and CAO) were down-regulated, whereas electron transport chain genes (PGR5, PGRL1A, PGRL1B, petH, and ndhH) were up-regulated. FF inhibited linear electron transfer (LET) and activated cyclic electron transfer (CET), which was consistent with the results of the chlorophyll fluorescence parameters. The photosynthetic carbon assimilation pathway was altered, the C3 pathway enzyme Ribulose1,5-bisphosphatecarboxylase/oxygenase (RuBisCO) was affected, C4 enzyme ((phosphoenolpyruvate carboxykinase (PEPCK), pyruvate orthophosphate dikinase (PPDK), malate dehydrogenase (MDH), and phosphoenolpyruvate carboxylase (PEPC))) and related genes were significantly up-regulated, suggesting that the C3 pathway is converted to C4 pathway for self-protection. The key enzymes involved in photorespiration, glycolate oxidase (GO) and catalase (CAT), responded positively, photosynthetic phosphorylation was inhibited, and ATP content and H+-ATPase activity were suppressed, nutrient content (K, P, N, Ca, Mg, Fe, Cu, Zn, Mn, and Ni) significantly affected. Transcriptomic analysis showed that FF and PS-MPs severely affected the photosynthetic capacity of rice seedlings, including photosystem I, photosystem II, non-photochemical quenching coefficients, and photosynthetic electron transport.

The relationship between future time perspective and suicide ideation in college students: Multiple mediating effects of anxiety and depression.

Background: Suicide ideation has high prevalence in adolescents, better future time perspective is considered a protective role for anxiety, depression, and suicide ideation. However, the impact of future time perspective on suicide ideation remains unclear, especially when anxiety and depression as mediating roles. Methods: A cross-sectional study of college students was performed in Chongqing, China. There are 851 students enrolled in this study and we distribute questionnaires through the WeChat platform to obtain data in 2023. We conducted Pearson correlation analysis and descriptive statistics. Model 6 in PROCESS 4.0 was used to test the multiple mediating effect. Results: College students who have higher future time perspective are associated with a lower risk of anxiety, depression, and suicide ideation. Future time perspective not only affects suicide ideation directly, but also influence it by means of two mediating pathways: ①depression, the mediation effect is 37.41 %; ②the multiple mediating effects of anxiety and depression with a mediating effect of 29.68 %. Conclusion: Higher future time perspective functions as a protective role in anxiety, depression, and suicide ideation; future time perspective can affect and predict the occurrence of suicide ideation by influencing anxiety and depression in college students. This conclusion will be a novel and insightful part of adolescent mental health research, and provide a new perspective to prevent college students from committing suicide in the future.

A T-Cell-Derived 3-Gene Signature Distinguishes SARS-CoV-2 from Common Respiratory Viruses.

Research on the host responses to respiratory viruses could help develop effective interventions and therapies against the current and future pandemics from the host perspective. To explore the pathogenesis that distinguishes SARS-CoV-2 infections from other respiratory viruses, we performed a multi-cohort analysis with integrated bioinformatics and machine learning. We collected 3730 blood samples from both asymptomatic and symptomatic individuals infected with SARS-CoV-2, seasonal human coronavirus (sHCoVs), influenza virus (IFV), respiratory syncytial virus (RSV), or human rhinovirus (HRV) across 15 cohorts. First, we identified an enhanced cellular immune response but limited interferon activities in SARS-CoV-2 infection, especially in asymptomatic cases. Second, we identified a SARS-CoV-2-specific 3-gene signature (CLSPN, RBBP6, CCDC91) that was predominantly expressed by T cells, could distinguish SARS-CoV-2 infection, including Omicron, from other common respiratory viruses regardless of symptoms, and was predictive of SARS-CoV-2 infection before detectable viral RNA on RT-PCR testing in a longitude follow-up study. Thereafter, a user-friendly online tool, based on datasets collected here, was developed for querying a gene of interest across multiple viral infections. Our results not only identify a unique host response to the viral pathogenesis in SARS-CoV-2 but also provide insights into developing effective tools against viral pandemics from the host perspective.

Postmenopausal endometrial non-benign lesion risk classification through a clinical parameter-based machine learning model.

OBJECTIVE: This study aimed to develop and evaluate a machine learning model utilizing non-invasive clinical parameters for the classification of endometrial non-benign lesions, specifically atypical hyperplasia (AH) and endometrioid carcinoma (EC), in postmenopausal women. METHODS: Our study collected clinical parameters from a cohort of 999 patients with postmenopausal endometrial lesions and conducted preprocessing to identify 57 relevant characteristics from these irregular clinical data. To predict the presence of postmenopausal endometrial non-benign lesions, including atypical hyperplasia and endometrial cancer, we employed various models such as eXtreme Gradient Boosting (XGBoost), Random Forest (RF), Logistic Regression (LR), Support Vector Machine (SVM), Back Propagation Neural Network (BPNN), as well as two ensemble models. Additionally, a test set was performed on an independent dataset consisting of 152 patients. The performance evaluation of all models was based on metrics including the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, precision, and F1 score. RESULTS: The RF model demonstrated superior recognition capabilities for patients with non-benign lesions compared to other models. In the test set, it attained a sensitivity of 88.1% and an AUC of 0.93, surpassing all alternative models evaluated in this study. Furthermore, we have integrated this model into our hospital's Clinical Decision Support System (CDSS) and implemented it within the outpatient electronic medical record system to continuously validate and optimize its performance. CONCLUSIONS: We have trained a model and deployed a system with high discriminatory power that may provide a novel approach to identify patients at higher risk of postmenopausal endometrial non-benign lesions who may benefit from more tailored screening and clinical intervention.

Ketoprofen exposure perturbs nitrogen assimilation and ATP synthesis in rice roots: An integrated metabolome and microbiome analysis.

Ketoprofen, a commonly used non-steroidal anti-inflammatory drug (NSAID), can enter farmland environments via sewage irrigation and manure application and is toxic to plants. However, there have been relatively few studies on the association of ketoprofen with nitrogen (N) assimilation and metabolic responses in plants. Accordingly, the goal of this study was to investigate the effects of ketoprofen on ATP synthesis and N assimilation in rice roots. The results showed that with increasing ketoprofen concentration, root vitality, respiration rate, ATP content, and H+-ATPase activity decreased and plasma membrane permeability increased. The expressions of OSA9, a family III H+-ATPase gene, and OSA6 and OSA10, family IV genes, were upregulated, indicating a response of the roots to ketoprofen. Nitrate, ammonium, and free amino acids content decreased with increased ketoprofen. The levels of enzymes involved in N metabolism, namely nitrate reductase, nitrite reductase, glutamine synthetase, glutamate synthetase, and glutamate dehydrogenase, also decreased under ketoprofen treatment. Principal component analysis revealed that ketoprofen treatment can significantly affect energy synthesis and nitrogen assimilation in rice roots, while these effects can be alleviated by the antioxidant response. Most of the metabolite contents increased, including amino acids, carbohydrates, and secondary metabolites. Key metabolic pathways, namely substance synthesis and energy metabolism, were found to be disrupted. Microbiome analysis showed that community diversity and richness of rice root microorganisms in solution increased with increasing levels of ketoprofen treatment, and the microbial community structure and metabolic pathways significantly changed. The results of this study provides new insights into the response of rice roots to ketoprofen.

Attenuation of Microglial Activation and Pyroptosis by Inhibition of P2X7 Pathway Promotes Photoreceptor Survival in Experimental Retinal Detachment.

Purpose: Photoreceptor (PR) death is the ultimate cause of irreversible vision loss in retinal detachment (RD). Although microglial infiltration in the subretinal space (SRS) was observed after RD, the molecular mechanism underlying microglial activation and the outcomes of infiltrating microglia remain unclear. We aimed to uncover the mechanism of initiation of microglial activation to help explore potential therapy to promote PR survival. Methods: An RD model was conducted by injecting sodium hyaluronate into SRS of C57BL/6J wild type mice. Adenosine triphosphate (ATP) was measured by a ATP Microplate Assay Kit. Bioinformatics analysis was used to evaluate the upregulated receptor relating to ATP binding in human datasets and mouse transcriptomes of RD. Expression of P2X7, its downstream signaling pathways, and microglial pyroptosis were confirmed by qPCR, WB, and immunofluorescence in vivo and in vitro. The cell viability of PR was measured by cell counting kit-8. Brilliant Blue G, a P2X7 antagonist, was subretinally or intraperitoneally injected to inhibit microglial activation in vivo and was applied for microglia cell line treatment in vitro. The decrease in microglial activation and pyroptosis was detected by immunofluorescence and WB. The protective effect on PR was measured by hematoxylin and eosin staining, TUNEL assay, and electroretinogram analysis. Results: The results showed that extracellular ATP released in the SRS after RD triggered P2X7 activation and attracted microglia. The downstream cascade of inflammasome activation induced by P2X7 activation contributed to microglial pyroptosis and then to PR death. ATP-activated microglia led to PR death in vitro. P2X7 blockade rescued PR morphologically and functionally by inhibiting microglial activation and pyroptosis. Conclusions: These results elucidate that ATP-induced P2X7-mediated microglial activation leads to microglial pyroptosis, contributing to PR death. Appropriate inhibition of microglial pyroptosis might serve as a pharmacotherapeutic strategy for decreasing PR death in RD.

Polystyrene microplastic attenuated the toxic effects of florfenicol on rice (Oryza sativa L.) seedlings in hydroponics: From the perspective of oxidative response, phototoxicity and molecular metabolism.

Antibiotics and microplastics (MPs) are two emerging pollutants in agroecosystems, however the effects of co-exposure to antibiotics and MPs remain unclear. The toxicity of florfenicol (FF) and polystyrene microplastics (PS-MPs) on rice seedlings was investigated. FF and PS-MPs caused colloidal agglomeration, which changed the environmental behavior of FF. FF inhibited rice growth and altered antioxidant enzyme (superoxide dismutase, peroxidase, and catalase) activities, leading to membrane lipid peroxidation; impaired photosynthetic systems, decreased photosynthetic pigments (Chlorophyll a, Chlorophyll b, and carotene), chlorophyll precursors (Proto IX, Mg-Proto IX, and Pchlide), photosynthetic and respiratory rates. The key photosynthesis related genes (PsaA, PsaB, PsbA, PsbB, PsbC, and PsbD) were significantly down-regulated. The ultrastructure of mesophyll cells was destroyed with chloroplast swelling, membrane surface blurring, irregular thylakoid lamellar structure, and number of peroxisomes increased. PS-MPs mitigated FF toxicity, and the IBR index values showed that 10 mg∙L-1 PS-MPs were more effective. Metabolomic analysis revealed that the abundance of metabolites and metabolic pathways were altered by FF, was greater than the combined "MPs-FF" contamination. The metabolism of amino acids, sugars, and organic acids were severely interfered. Among these, 15 metabolic pathways were significantly altered, with the most significant effects on phenylalanine metabolism and the citric acid cycle (p < 0.05).

How Late-Life Working Affects Depression Among Retirement-Aged Workers? An Examination of the Influence Paths of Job-Related (Non-Job-Related) Physical Activity and Social Contact.

PURPOSE: This study investigates the influence paths that late career participation affects depression of older workers. METHOD: The data of China Health and Retirement Longitudinal Study (2018) are used. Those who have reached the statutory retirement age in China (>60 years for males/>55 years for females) are investigated. RESULTS: Late career participation may positively affect job-related physical activity and social contact (2.110 and 0.028, P < 0.01) and negatively affect non-job-related physical activity (-0.343, P < 0.01). Besides, job-related physical activity may exacerbate depression symptoms among older workers (0.017, P < 0.01), whereas non-job-related physical activity and social contact may alleviate it (-0.015 and -0.038, P < 0.01). CONCLUSIONS: Late career participation could be associated with depression through different pathways involving job-related (and non-job-related) physical activity and social contact. The overall impact of late career participation on depression would depend on which influence pathway is dominant.

The Role of Indoleamine 2, 3-Dioxygenase 1 in Regulating Tumor Microenvironment.

Indoleamine 2, 3-dioxygenase 1 (IDO1) is a rate-limiting enzyme that metabolizes an essential amino acid tryptophan (Trp) into kynurenine (Kyn), and it promotes the occurrence of immunosuppressive effects by regulating the consumption of Trp and the accumulation of Kyn in the tumor microenvironment (TME). Recent studies have shown that the main cellular components of TME interact with each other through this pathway to promote the formation of tumor immunosuppressive microenvironment. Here, we review the role of the immunosuppression mechanisms mediated by the IDO1 pathway in tumor growth. We discuss obstacles encountered in using IDO1 as a new tumor immunotherapy target, as well as the current clinical research progress.

Prevalence and Factors Associated with BRCA1/2 Gene Mutation in Chinese Populations with Breast Cancer.

Objective: We aimed to evaluate the prevalence of BRCA1 and BRCA2 mutations in Chinese populations with breast cancer. Factors associated with BRCA1 and BRCA2 mutations are also evaluated. Methods: This was a cross-sectional study, and patients with breast cancer were included. Data on clinical characteristics, information of breast cancer, and BRCA1 and BRCA2 mutations were extracted. Patients were divided into the carrier and noncarrier groups. Results: A total of 368 patients were included. Compared to the noncarrier group (n = 240), patients in the carrier group (n = 128) were younger and more likely to have breast cancer at age <40 years. Of the overall 128 patients in the carrier groups, 58 had BRCA1 mutation and 70 had BRCA2 mutation. Among patients with early onset breast cancer, there was no difference in the prevalence of BRCA1 and BRCA2 (20.7% vs 17.1%, P = 0.35). While among patients with a family history of breast/ovarian cancer, BRCA2 mutation was more prevalent than BRCA1 mutation (54.3% vs 44.8%, P = 0.01); and among patients with triple-negative breast cancer, BRCA1 mutation was more prevalent than BRCA2 mutation (34.5% vs 28.6%, P = 0.04). After adjusting for covariates, factors associated with BRCA1 mutation included breast cancer diagnosed <40 years, tumor size >2 cm, and lymph node metastasis; and after adjusting for covariates, factors associated with BRCA2 mutation included age, tumor size >2 cm, and triple-negative breast cancer. Conclusion: The prevalence of BRCA1 and BRCA2 mutations varied according to three specific subgroups. Factors associated with BRCA1 and BRCA2 mutations were differential.

Predictive value of soluble ST-2 for changes of cardiac function and structure in breast cancer patients receiving chemotherapy.

The current study was to evaluate soluble ST-2 level and left ventricular ejection fraction (LVEF) in patients with breast cancer receiving doxorubicin or trastuzumab treatment for 6 months and determine whether soluble ST-2 level can be used to predictive left ventricular function impairment.Patients who were diagnosed as having breast cancer receiving doxorubicin or trastuzumab or combined therapy were enrolled. Demographic data, prior medical history and related medical therapy, and site and stage of breast cancer information were collected from electronic health record. Fasting blood was used to detect soluble ST-2 and brain natriuretic peptide (BNP) levels before and after 6 months doxorubicin or trastuzumab therapy. Echocardiography was performed before and after 6 months of doxorubicin or trastuzumab therapy.Participants were divided into 3 groups based on tertiary soluble ST-2 level. Compared with 1st tertiary group, patients in the 3rd tertiary group had higher proportion receiving combined therapy (14.3% vs 4.7%, P < .05). Baseline soluble ST-2 level was similar across groups. After 6 months' therapy, soluble ST-2 level was significantly higher in the 3rd tertiary group. Pearson correlation analysis showed that soluble ST-2 level was positively correlated with left ventricular volume and E/e' ratio while negatively correlated with LVEF. Doxorubicin, trastuzumab, combined therapy, soluble ST-2 level, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker treatment were all independently associated with LVEF change.In breast cancer patients receiving doxorubicin or trastuzumab therapy, soluble ST-2 level can be used to predict cardiac function and structure changes.

Theoretical exploration of control factors for the high-order harmonic generation (HHG) spectrum in two-color field.

In this work, the laser-parameter effects on the high-order harmonic generation (HHG) spectrum and attosecond trains by mixing two-color laser field, a visible light field of 800 nm and a mid-infrared (mid-IR) laser pulses of 2400 nm, are theoretically demonstrated for the first time. Different schemes are applied to discuss the function of intensity, carrier-envelope phase (CEP) and pulse duration on the generation of an isolated attosecond pulse. As a consequence, an isolated 16as pulse is obtained by Fourier transforming an ultrabroad XUV continuum of 208 eV with the fundamental field of duration of 6 fs, 9×10(14)W/cm2 of intensity, the duration of 12 fs, the CEPs of the two driving pulses of -π and the relative strength ratio √R=0.2.