Aberrant follicular regulatory T cells associate with immunoglobulin hyperproduction in nasal polyps with ectopic lymphoid tissues.

BACKGROUND: Ectopic lymphoid tissues (eLTs) and associated follicular helper T (TFH) cells contribute to local immunoglobulin hyperproduction in nasal polyps (NPs). Follicular regulatory T (TFR) cells in secondary lymphoid organs counteract TFH cells and suppress immunoglobulin production; however, the presence and function of TFR cells in eLTs in peripheral diseased tissues remain poorly understood. OBJECTIVE: We sought to investigate the presence, phenotype, and function of TFR cells in NPs. METHODS: The presence, abundance, and phenotype of TFR cells in NPs were examined using single-cell RNA sequencing, immunofluorescence staining, and flow cytometry. Sorted polyp and circulating T-cell subsets were cocultured with autologous circulating naïve B cells, and cytokine and immunoglobulin production were measured by ELISA. RESULTS: TFR cells were primarily localized within eLTs in NPs. TFR cell frequency and TFR cell/TFH cell ratio were decreased in NPs with eLTs compared with NPs without eLTs and control inferior turbinate tissues. TFR cells displayed an overlapping phenotype with TFH cells and FOXP3+ regulatory T cells in NPs. Polyp TFR cells had reduced CTLA-4 expression and decreased capacity to inhibit TFH cell-induced immunoglobulin production compared with their counterpart in blood and tonsils. Blocking CTLA-4 abolished the suppressive effect of TFR cells. Lower vitamin D receptor expression was observed on polyp TFR cells compared with TFR cells in blood and tonsils. Vitamin D treatment upregulated CTLA-4 expression on polyp TFR cells and restored their suppressive function in vitro. CONCLUSIONS: Polyp TFR cells in eLTs have decreased CLTA-4 and vitamin D receptor expression and impaired capacity to suppress TFH cell-induced immunoglobulin production, which can be reversed by vitamin D treatment in vitro.

Global, regional and national temporal trends in prevalence for musculoskeletal disorders in women of childbearing age, 1990-2019: an age-period-cohort analysis based on the Global Burden of Disease Study 2019.

OBJECTIVES: To provide an overview and in-depth analysis of temporal trends in prevalence of musculoskeletal (MSK) disorders in women of childbearing age (WCBA) at global, regional and national levels over the last 30 years, with a special focus on their associations with age, period and birth cohort. METHODS: Estimates and 95% uncertainty intervals (UIs) for MSK disorders prevalence in WCBA were extracted from the Global Burden of Diseases, Injuries and Risk Factors Study 2019. An age-period-cohort model was adopted to estimate the overall annual percentage change of prevalence (net drift, % per year), annual percentage change of prevalence within each age group (local drift, % per year), fitted longitudinal age-specific rates adjusted for period deviations (age effects) and period/cohort relative risks (period/cohort effects) from 1990 to 2019. RESULTS: In 2019, the global number of MSK disorders prevalence in WCBA was 354.57 million (95% UI: 322.64 to 387.68). Fifty countries had at least one million prevalence, with India, China, the USA, Indonesia and Brazil being the highest accounting for 51.03% of global prevalence. From 1990 to 2019, a global net drift of MSK disorders prevalence in WCBA was -0.06% (95% CI: -0.07% to -0.05%) per year, ranging from -0.09% (95% CI: -0.10% to -0.07%) in low-middle sociodemographic index (SDI) region to 0.10% (95% CI: 0.08% to 0.12%) in high-middle SDI region, with 138 countries presenting increasing trends, 24 presenting decreasing trends and 42 presenting relatively flat trends. As reflected by local drift, higher SDI regions had more age groups showing rising prevalence whereas lower SDI regions had more declining prevalence. Globally, an increasing occurrence of MSK disorders prevalence in WCBA beyond adolescent and towards the adult stage has been prominent. Age effects illustrated similar patterns across different SDI regions, with risk increasing with age. High SDI region showed generally lower period risks over time, whereas others showed more unfavourable period risks. High, high-middle and middle SDI regions presented unfavourable prevalence deteriorations, whereas others presented favourable prevalence improvements in successively birth cohorts. CONCLUSIONS: Although a favourable overall temporal trend (net drift) of MSK disorders prevalence in WCBA was observed over the last 30 years globally, there were 138 countries showing unfavourable rising trends, coupled with deteriorations in period/cohort risks in many countries, collectively raising concerns about timely realisation of the Targets of Sustainable Development Goal. Improvements in the MSK disorders-related prevention, management and treatment programmes in WCBA could decline the relative risk for successively younger birth cohorts and for all age groups over period progressing.

Immune signatures predict response to house dust mite subcutaneous immunotherapy in patients with allergic rhinitis.

BACKGROUND: Identifying predictive biomarkers for allergen immunotherapy response is crucial for enhancing clinical efficacy. This study aims to identify such biomarkers in patients with allergic rhinitis (AR) undergoing subcutaneous immunotherapy (SCIT) for house dust mite allergy. METHODS: The Tongji (discovery) cohort comprised 72 AR patients who completed 1-year SCIT follow-up. Circulating T and B cell subsets were characterized using multiplexed flow cytometry before SCIT. Serum immunoglobulin levels and combined symptom and medication score (CSMS) were assessed before and after 12-month SCIT. Responders, exhibiting ≥30% CSMS improvement, were identified. The random forest algorithm and logistic regression analysis were used to select biomarkers and establish predictive models for SCIT efficacy in the Tongji cohort, which was validated in another Wisco cohort with 43 AR patients. RESULTS: Positive SCIT response correlated with higher baseline CSMS, allergen-specific IgE (sIgE)/total IgE (tIgE) ratio, and frequencies of Type 2 helper T cells, Type 2 follicular helper T (TFH2) cells, and CD23+ nonswitched memory B (BNSM) and switched memory B (BSM) cells, as well as lower follicular regulatory T (TFR) cell frequency and TFR/TFH2 cell ratio. The random forest algorithm identified sIgE/tIgE ratio, TFR/TFH2 cell ratio, and BNSM frequency as the key biomarkers discriminating responders from nonresponders in the Tongji cohort. Logistic regression analysis confirmed the predictive value of a combination model, including sIgE/tIgE ratio, TFR/TFH2 cell ratio, and CD23+ BSM frequency (AUC = 0.899 in Tongji; validated AUC = 0.893 in Wisco). CONCLUSIONS: A T- and B-cell signature combination efficiently identified SCIT responders before treatment, enabling personalized approaches for AR patients.

Changes in frailty and depressive symptoms among middle-aged and older Chinese people: a nationwide cohort study.

BACKGROUND AND AIMS: The older people bears a severe burden of disease due to frailty and depressive symptoms, however, the results of association between the two in the older Chinese people have been conflicting. Therefore, this study aimed to investigate the developmental trajectories and interactions of frailty and depressive symptoms in the Chinese middle-aged and older adults. METHODS: The study used four waves of data from 2011, 2013, 2015 and 2018 in the China Health and Retirement Longitudinal Study (CHARLS) database, focused on middle-aged and older people ≥ 45 years of age, and analyzed using latent growth models and cross-lagged models. RESULTS: The parallel latent growth model showed that the initial level of depressive symptoms had a significant positive predictive effect on the initial level of frailty. The rate of change in depressive symptoms significantly positively predicted the rate of change in frailty. The initial level of frailty had a significant positive predictive effect on the initial level of depressive symptoms, but a significant negative predictive effect on the rate of change in depressive symptoms. The rate of change in frailty had a significant positive predictive effect on the rate of change in depressive symptoms. The results of the cross-lagged analysis indicated a bidirectional causal association between frailty and depressive symptoms in the total sample population. Results for the total sample population grouped by age and gender were consistent with the total sample. CONCLUSIONS: This study recommends advancing the age of concern for frailty and depressive symptoms to middle-aged adults. Both men and women need early screening and intervention for frailty and depressive symptoms to promote healthy aging.

Chronic exposure to ambient air pollution and the risk of non-alcoholic fatty liver disease: A cross-sectional study in Taiwan and Hong Kong.

BACKGROUND: Information on the relation of air pollution with non-alcoholic fatty liver disease (NAFLD) is scarce. We thus conducted a large cross-sectional study in Asia to investigate the role of air pollution in NAFLD. METHODS: We recruited 329,048 adults (mean age: 41.0 years) without other liver disease (hepatitis and cirrhosis) or excessive alcohol consumption in Taiwan and Hong Kong from 2001 to 2018. The concentrations of nitrogen dioxide (NO2) and ozone (O3) were estimated using a space-time regression model, and the concentrations of fine particulate matter (PM2.5) was evaluated using a satellite-based spatio-temporal model. NAFLD was determined using either the fatty liver index (FLI) or the hepatic steatosis index (HSI). The NAFLD-related advanced fibrosis was defined according to BARD score or the fibrosis-4 (FIB-4). A logistic regression model was adopted to explore the relationships of ambient air pollution with the odds of NAFLD and NAFLD-related advanced fibrosis. RESULTS: We found positive relationships between PM2.5 and the odds of NAFLD and advanced fibrosis, with every standard deviation (SD, 7.5 µg/m3) increases in PM2.5 exposure being associated with a 10% (95% confidence interval [CI]: 9%-11%) increment in the prevalence of NAFLD and an 8% (95% CI: 7%-9%) increment in the prevalence of advanced fibrosis. Similarly, the prevalence of NAFLD and advanced fibrosis increased by 8% (95% CI: 7%-9%) and 7% (95% CI: 6%-8%) with per SD (18.9 µg/m3) increasement in NO2 concentration, respectively. Additionally, for every SD (9.9 µg/m3) increasement in O3 concentration, the prevalence of NAFLD and advanced fibrosis decreased by 12% (95% CI: 11%-13%) and 11% (95% CI: 9%-12%), respectively. CONCLUSION: Higher ambient PM2.5 and NO2 are linked with higher odds of NAFLD and advanced fibrosis. Our findings indicate that reducing PM2.5 and NO2 concentrations may be an effective way for preventing NAFLD. Further studies on O3 are warranted.

CircRSU1 alleviates LPS-induced human pulmonary microvascular endothelial cell injury by targeting miR-1224-5p/ITGA5 axis.

To investigate the potential functions and regulatory mechanism of circRSU1 on septic acute lung injury (sepsis-ALI) progression. We used lipopolysaccharide (LPS)-stimulated human pulmonary microvascular endothelial cells (HPMECs) to establish the cell model of sepsis-ALI in vitro. qRT-PCR and Western blotting were used for the detection of genes and proteins. The migration and tubulogenesis of HPMECs were assessed by transwell, wound healing, and tube formation assays. Inflammatory factors were detected by ELISA analysis. Cell permeability (PA) was determined by transendothelial resistance (TEER) and fluorescein isothiocyanate (FITC) with transwell assay. The interaction between miR-1224-5p and circRSU1 or ITGA5 (Integrin Subunit Alpha 5) was studied by dual-luciferase reporter and RNA pull-down assays. CircRSU1 expression was decreased after LPS treatment in HPMECs. Functionally, re-expression of circRSU1 in HPMECs could alleviate LPS-induced inflammatory response, the inhibition of cell migration and tube formation and enhancement of cell permeability. Mechanistically, circRSU1 acted as a sponge for miR-1224-5p. LPS treatment enhanced miR-1224-5p expression, and inhibition of miR-1224-5p reversed LPS-evoked HPMEC dysfunction mentioned above. Moreover, miR-1224-5p could abolish the protective effects of circRSU1 on HPMECs. In addition, miR-1224-5p directly targeted ITGA5, and circRSU1 was able to regulate ITGA5 expression via interacting with miR-1224-5p. CircRSU1 could alleviate LPS-induced HPMEC injury by miR-1224-5p/ITGA5 axis, indicating the potential molecular contribution of circRSU1 in sepsis-ALI.

Green preparation of CaO-based CO2 adsorbent by calcium-induced hydrogenation of shell wastes at room/moderate temperature.

Capturing CO2 using clamshell/eggshell-derived CaO adsorbent can not only reduce carbon emissions but also alleviate the impact of trash on the environment. However, organic acid was usually used, high-temperature calcination was often performed, and CO2 was inevitably released during preparing CaO adsorbents from shell wastes. In this work, CaO-based CO2 adsorbent was greenly prepared by calcium-induced hydrogenation of clamshell and eggshell wastes in one pot at room/moderate temperature. CO2 adsorption experiments were performed in a thermogravimetric analyzer (TGA). The adsorption performance of the adsorbents obtained from the mechanochemical reaction (BM-C/E-CaO) was superior to that of the adsorbents obtained from the thermochemical reaction (Cal-C/E-CaO). The CO2 adsorption capacity of BM-C-CaO at 650 °C is up to 36.82 wt%, but the adsorption decay rate of the sample after 20 carbonation/calcination cycles is only 30.17%. This study offers an alternative energy-saving method for greenly preparing CaO-based adsorbent from shell wastes.

Effects of comprehensive nursing intervention on quality of life, Self-efficacy, gastrointestinal reaction and immune function of patients with breast cancer undergoing chemotherapy.

Objective: To assess the effects of comprehensive nursing intervention on quality of life, self-efficacy, gastrointestinal reaction and immune function of patients with breast cancer undergoing chemotherapy. Methods: This was a retrospective study. One hundred and twenty patients receiving chemotherapy after breast cancer surgery were randomly divided into the experimental group and the control group(n=60) from January 2021 to January 2023. Patients in the perioperative period, the experimental group were given comprehensive nursing intervention, while those in the control group were given conventional specialist nursing intervention. The differences in quality of life, self-efficacy, gastrointestinal reaction, immune function and patient satisfaction between the two groups were compared and analyzed. Results: After the intervention, the SF-36 scores in the experimental group were significantly higher than those in the control group (P=0.00), the efficacy indicators were significantly improved compared to the control group(P=0.00); the scores of gastrointestinal symptoms in the experimental group were significantly lower than those in the control group after the intervention(P<0.05). The indexes of CD3+, CD4+ and CD4+/CD8+ in the experimental group after the intervention were significantly higher than those in the control group(P=0.00); The patient satisfaction in the experimental group was 100%, which was significantly higher than 92% in the control group, with statistically significant differences(P=0.02). Conclusion: Comprehensive nursing intervention leads to a variety of benefits in the treatment of patients with breast cancer during postoperative chemotherapy, such as relieving patients' gastrointestinal reactions, improving their immune function and quality of life, besides effectively improving their self-efficacy, which is worthy of clinical application.

Solar-Powered Interfacial Evaporation and Deicing Based on a 3D-Printed Multiscale Hierarchical Design.

Solar-powered interfacial heating has emerged as a sustainable technology for hybrid applications with minimal carbon footprints. Aerogels, hydrogels, and sponges/foams are the main building blocks for state-of-the-art photothermal materials. However, these conventional three-dimensional (3D) structures and related fabrication technologies intrinsically fail to maximize important performance-enhancing strategies and this technology still faces several performance roadblocks. Herein, monolithic, self-standing, and durable aerogel matrices are developed based on composite photothermal inks and ink-extrusion 3D printing, delivering all-in-one interfacial steam generators (SGs). Rapid prototyping of multiscale hierarchical structures synergistically reduce the energy demand for evaporation, expand actual evaporation areas, generate massive environmental energy input, and improve mass flows. Under 1 sun, high water evaporation rates of 3.74 kg m-2 h-1 in calm air and 25.3 kg m-2 h-1 at a gentle breeze of 2 m s-1 are achieved, ranking among the best-performing solar-powered interfacial SGs. 3D-printed microchannels and hydrophobic modification deliver an icephobic surface of the aerogels, leading to self-propelled and rapid removal of ice droplets. This work shines light on rational fabrication of hierarchical photothermal materials, not merely breaking through the constraints of solar-powered interfacial evaporation and clean water production, but also discovering new functions for photothermal interfacial deicing.

Discovery of an Abundant Viral Genus in Polar Regions through the Isolation and Genomic Characterization of a New Virus against Oceanospirillaceae.

The marine bacterial family Oceanospirillaceae, is well-known for its ability to degrade hydrocarbons and for its close association with algal blooms. However, only a few Oceanospirillaceae-infecting phages have been reported thus far. Here, we report on a novel Oceanospirillum phage, namely, vB_OsaM_PD0307, which has a 44,421 bp linear dsDNA genome and is the first myovirus infecting Oceanospirillaceae. A genomic analysis demonstrated that vB_OsaM_PD0307 is a variant of current phage isolates from the NCBI data set but that it has similar genomic features to two high-quality, uncultured viral genomes identified from marine metagenomes. Hence, we propose that vB_OsaM_PD0307 can be classified as the type phage of a new genus, designated Oceanospimyovirus. Additionally, metagenomic read mapping results have further shown that Oceanospimyovirus species are widespread in the global ocean, display distinct biogeographic distributions, and are abundant in polar regions. In summary, our findings expand the current understanding of the genomic characteristics, phylogenetic diversity, and distribution of Oceanospimyovirus phages. IMPORTANCE Oceanospirillum phage vB_OsaM_PD0307 is the first myovirus found to infect Oceanospirillaceae, and it represents a novel abundant viral genus in polar regions. This study provides insights into the genomic, phylogenetic, and ecological characteristics of the new viral genus, namely Oceanospimyovirus.

Ideal suppression of Bessel beam intensity oscillations with a vortex phase plate.

We propose what we believe to be a new kind of diffractive phase element, i.e., vortex phase plate (VPP) with phase singularities along the azimuth direction. Phase function of the proposed VPP is given analytically. Axial intensity oscillations of propagating Bessel beams are ideally suppressed by using the proposed VPP. Compared with the traditional amplitude mask, the proposed VPP takes such advantages as a simpler fabrication procedure and a lower cost.

Exceptional Non-Abelian Topology in Multiband Non-Hermitian Systems.

Defective spectral degeneracy, known as exceptional point (EP), lies at the heart of various intriguing phenomena in optics, acoustics, and other nonconservative systems. Despite extensive studies in the past two decades, the collective behaviors (e.g., annihilation, coalescence, braiding, etc.) involving multiple exceptional points or lines and their interplay have been rarely understood. Here we put forward a universal non-Abelian conservation rule governing these collective behaviors in generic multiband non-Hermitian systems and uncover several counterintuitive phenomena. We demonstrate that two EPs with opposite charges (even the pairwise created) do not necessarily annihilate, depending on how they approach each other. Furthermore, we unveil that the conservation rule imposes strict constraints on the permissible exceptional-line configurations. It excludes structures like Hopf link yet permits novel staggered rings composed of noncommutative exceptional lines. These intriguing phenomena are illustrated by concrete models which could be readily implemented in platforms like coupled acoustic cavities, optical waveguides, and ring resonators. Our findings lay the cornerstone for a comprehensive understanding of the exceptional non-Abelian topology and shed light on the versatile manipulations and applications based on exceptional degeneracies in nonconservative systems.

Identification of Inflammatory Endotypes by Clinical Characteristics and Nasal Secretion Biomarkers in Chronic Rhinosinusitis with Nasal Polyps.

INTRODUCTION: The emergency of biologics and surgical techniques targeting the specific inflammatory endotype in chronic rhinosinusitis with nasal polyps (CRSwNP) asks for efficient identification of patients with different endotypes. Although mucosal IL-4, IL-5, IL-13, and IgE have been used to define type 2 (T2) inflammation, the optimal one remains unclear. In this study, we aimed to determine the optimal anchor for T2 inflammation and identify clinical characteristics and nasal secretion biomarkers predicting different endotypes in CRSwNP. METHODS: Six mediators in sinonasal tissue and 36 mediators in nasal secretion samples were detected by the Bio-Plex suspension array system. Mucosal IFN-γ and IL-17A levels were used to define the T1 and T3 endotype, respectively. The efficacy of mucosal IL-4, IL-5, IL-13, and IgE to define the T2 endotype was compared. The power of clinical characteristics and nasal secretion biomarkers to predict the T1, T2, and T3 endotype was analyzed. RESULTS: Among mucosal IL-4, IL-5, IL-13, and IgE, IL-13 was the best one to coincide with the expression of other T2 biomarkers. A combination of atopy, facial pain symptom score, ethmoid/maxillary computed tomography score ratio, and blood eosinophil percentage had a moderate predictive performance for T2 endotype (area under the receiver operating curve [AUC] = 0.815), comparable to that of nasal secretion IL-5 (AUC = 0.819). For the T3 endotype, nasal secretion IL-1Rα identified it with an AUC value of 0.756. No efficient marker for the T1 endotype was found. CONCLUSION: IL-13 is a primary anchor for the T2 endotype in CRSwNP. Clinical characteristics and nasal secretion biomarkers are helpful for identifying the T2 and T3 endotype of CRSwNP.

Influencing factors of self-disclosure and its impact on quality of life in patients with systemic lupus erythematosus.

BACKGROUND: Self-disclosure may enhance positive illness perceptions, whereas patients with systemic lupus erythematosus (SLE) always facing negative illness perceptions due to multiple reasons, so elucidation of factors affecting self-disclosure may facilitate the development of quality of life. METHODS: A total of 161 hospitalized patients with SLE were recruited. Scales on demographic and clinical characteristics, self-disclosure, psychosocial status (e.g. Social Support Rating Scale - SSRS) and quality of life were used to collect related information from clients. Univariate analysis was performed by Kruskal-Wallis rank-sum test or chi-square test, and multivariate analysis by ordinal logistic regression. RESULTS: Social support, drinking, depression and cause of hospitalization were found to be influencing factors of self-disclosure. Multiple logistic regression analyses revealed that the significant and independent factors associated with self-disclosure in patients with SLE were social support, drinking and depression. Domains of LupusQoL, except physical health and fatigue, were positively correlated with self-disclosure. CONCLUSIONS: With the increase of social support, the level of self-disclosure become worse, drinking, depression and cause of hospitalization are risk factors for it. Moreover, the level of self-disclosure is positively related to the LupusQoL. Medical staff should formulate effective measures according to the results to improve self-disclosure in patients with SLE and promote their quality of life.

Type 2 Biomarkers for the Indication and Response to Biologics in CRSwNP.

PURPOSE OF REVIEW: Three biologics targeting type 2 inflammation have been approved for the treatment of severe and uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP). Nevertheless, around 40-60% of patients do not respond well to these biological treatments. Selecting appropriate patients is crucial to improve treatment outcome of biologics. This review summarizes the literature data on type 2 biomarkers, with a specific focus on the indication to biologics for severe CRSwNP. RECENT FINDINGS: No consensus has been reached on how to define mucosal type 2 inflammation in CRSwNP. Clinical markers (e.g., 22-item Sino-nasal Outcome Test (SNOT-22) score, Lund-Mackay CT score (LMS), ethmoid/maxillary sinus CT score, and CT-radiomics), nasal secretion biomarkers (e.g., eosinophil cationic protein and interleukin-5), blood and nasal cytology eosinophil counts, and nasal swab eosinophil peroxidase activity have been reported to be associated with type 2 inflammation in CRSwNP. The time duration since the last surgery, SNOT-22 score at 1 week of treatment, and baseline serum osteoprotegerin levels might indicate the response to dupilumab. LMS and asthma control test scores were found to have moderate predictive value for acceptable improvement after 24-week treatment of omalizumab. High blood eosinophil levels at baseline were associated with treatment response to mepolizumab and benralizumab. Although several clinical and biological markers might be associated with type 2 inflammation and response to biologics in patients with CRSwNP, their validity requires further investigation. Identifying clinically applicable biomarkers for biologic treatment holds significant promise for advancing personalized approaches to biologics and optimizing treatment outcomes for patients with CRSwNP.

Bidirectional causal relationship between depression and frailty: a univariate and multivariate Mendelian randomisation study.

BACKGROUND: cumulative evidence from cohort studies suggested that there were inconsistent conclusions as to whether there was a bidirectional association between depression and frailty. Therefore, this study used a bidirectional two-sample Mendelian randomisation (MR) study to investigate the causal relationship between depression and frailty. METHODS: we performed univariate and multivariate bidirectional MR analyses to assess the causal association between depression and frailty. Independent genetic variants associated with depression and frailty were selected as instrumental variables. Inverse variance weighted (IVW), MR-Egger, weighted median and weighted mode were mainly used in univariate MR analysis. Multivariate MR (MVMR) analyses used multivariable inverse variance-weighted methods to individually and jointly adjust for three potential confounders, body mass index (BMI), age at menarche (AAM) and waist-to-hip ratio (WHR, adjusted for BMI). RESULTS: univariate MR analysis showed a positive causal relationship between depression and risk of frailty (IVW, odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.23-1.37, P = 6.54E-22). Causal relationship between frailty and risk of depression (IVW, OR = 1.69, 95% CI = 1.33-2.16, P = 2.09E-05). MVMR analysis revealed that the bidirectional causal association between depression and frailty remained after adjusting for three potential confounders, BMI, AAM and WHR (adjusted for BMI), individually and in combination. CONCLUSIONS: our findings supported a causal relationship between genetically predicted depression and frailty in both directions.

A 71-year-old male with a life-threatening recurrence of hemolytic anemia, thrombocytopenia, and acute kidney injury after pembrolizumab therapy: a case report.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. However, their use has been restricted in patients with preexisting autoimmune diseases due to concerns about increased risk of immune-related adverse events (irAEs). CASE PRESENTATION: We present a case of a patient with stage IV lung adenocarcinoma and a history of complement-mediated autoimmune hemolytic anemia in remission. After receiving a single dose of pembrolizumab, the patient experienced life-threatening recurrent hemolytic anemia, de novo thrombocytopenia, diarrhea, myocarditis, and acute kidney injury. Laboratory tests confirmed the diagnosis of Evan's syndrome, with positive PAIgG and direct antiglobulin test. Treatment with intravenous methylprednisolone at a dose of 2 mg/kg resulted in a favorable response, with resolution of symptoms and rapid recovery of kidney function. The probable cause of pre-renal hypoperfusion (evidenced by a BUN-to-creatinine ratio of 48.1) leading to acute tubular injury was attributed to pembrolizumab-induced diarrhea. CONCLUSIONS: This case illustrates a life-threatening recurrence of complement-mediated autoimmune hemolytic anemia induced by ICIs. Clinicians should carefully consider the expected efficacy and potential toxicity before initiating ICIs therapy in patients with preexisting autoimmune diseases. Additionally, the occurrence of acute kidney injury during ICIs therapy adds complexity and requires careful differential diagnosis.

Chronic exposure to ambient PM2.5/NO2 and respiratory health in school children: A prospective cohort study in Hong Kong.

Despite increasing concerns about the detrimental effects of air pollution on respiratory health, limited evidence is available on these effects in the Hong Kong population, especially in children. In this prospective cohort study between 2012 and 2017, we aimed to investigate the associations between exposure to air pollution (concentrations of fine particulate matter [PM2.5] and nitrogen dioxide [NO2]) and respiratory health (lung function parameters and respiratory diseases and symptoms) in schoolchildren. We recruited 5612 schoolchildren aged 6-16 years in Hong Kong. We estimated the annual average concentrations of ambient PM2.5 and NO2 at each participant's address using spatiotemporal models. We conducted spirometry tests on all participants to measure their lung function parameters and used a self-administered questionnaire to collect information on their respiratory diseases and symptoms and a wide range of covariates. Linear mixed models were used to investigate the associations between exposure to air pollution and lung function. Mixed-effects logistic regression models with random effects were used to investigate the associations of exposure to air pollution with respiratory diseases and symptoms. In all of the participants, every 5-µg/m3 increase in the ambient PM2.5 concentration was associated with changes of - 13.90 ml (95 % confidence interval [CI]: -23.65 ml, -4.10 ml), - 4.20 ml (-15.60 ml, 7.15 ml), 27.20 ml/s (-3.95 ml/s, 58.35 ml/s), and - 19.80 ml/s (-38.35 ml/s, -1.25 ml/s) in forced expiratory volume in 1 s, forced vital capacity, peak expiratory flow, and maximal mid-expiratory flow, respectively. The corresponding lung function estimates for every 5-µg/m3 increase in the ambient NO2 concentration were - 2.70 ml (-6.05 ml, 0.60 ml), - 1.40 ml (-5.40 ml, 2.60 ml), - 6.60 ml/s (-19.75 ml/s, 6.55 ml/s), and - 3.05 ml/s (-11.10 ml/s, 5.00 ml/s), respectively. We did not observe significant associations between PM2.5/NO2 exposure and most respiratory diseases and symptoms. Stratified analyses by sex and age showed that the associations between exposure to air pollution and lung function parameters were stronger in male participants and older participants (11-14 year old group) than in female participants and younger participants (6-10 year old group), respectively. Our results suggest that chronic exposure to air pollution is detrimental to the respiratory health of schoolchildren, especially that of older boys. Our findings reinforce the importance of air pollution mitigation to protect schoolchildren's respiratory health.

Targeting lipid metabolism with natural products: A novel strategy for gastrointestinal cancer therapy.

Gastrointestinal cancer (GIC), including gastric cancer and colorectal cancer, is a common malignant tumor originating from gastrointestinal epithelial cells. Although the pathogenesis of GIC remains unclear, aberrant lipid metabolism has emerged as a hallmark of cancer. Several enzymes, proteins, and transcription factors are involved in lipid metabolism reprogramming in GIC, and their abnormal expression can promote lipid synthesis and accumulation of lipid droplets through numerous mechanisms, thereby affecting the growth, proliferation, and metastasis of GIC cells. Studies show that some natural compounds, including flavonoids, alkaloids, and saponins, can inhibit the de novo synthesis of lipids in GIC, reduce the level of lipid accumulation, and subsequently, inhibit the occurrence and development of GIC by regulating Sterol regulatory element-binding protein 1 (SREBP-1), adenosine monophosphate-activated protein kinase (AMPK), 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), phosphatidylinositol-3-kinase/Akt and the mammalian target of rapamycin PI3K/Akt/mTOR, amongst other targets and pathways. Therefore, targeting tumor lipid metabolism is the focus of anti-gastrointestinal tumor therapy. Although most natural products require further high-quality studies to firmly establish their clinical efficacy, we review the potential of natural products in the treatment of GIC and summarize the application prospect of lipid metabolism as a new target for the treatment of GIC, hoping to provide a reference for drug development for gastrointestinal tumors.

Extrafollicular PD-1highCXCR5-CD4+ T cells participate in local immunoglobulin production in nasal polyps.

BACKGROUND: Local immunoglobulin hyperproduction is observed in nasal polyps (NPs) with and without ectopic lymphoid tissues (eLTs). OBJECTIVE: Our aim was to identify the T-cell subsets involved in local immunoglobulin production independent of eLTs in NPs. METHODS: The localization, abundance, and phenotype of CD4+ T-cell subsets were studied by immunofluorescence, flow cytometry, and single-cell RNA sequencing. Purified nasal T-cell subsets were cultured with autologous peripheral naive B cells to explore their function. Programmed death ligand 1 and programmed death ligand 2 expression in NPs was investigated by immunofluorescence staining and flow cytometry. RESULTS: Accumulation of PD-1highCXCR5-CD4+ T cells outside lymphoid aggregates was found in NPs. Nasal PD-1highCXCR5-CD4+ T cells were characterized by a unique phenotype that was related to B-cell help and tissue residency and distinct from PD-1-/intCXCR5- and CXCR5+ CD4+ T cells in NPs as well as PD-1highCXCR5highCD4+ follicular helper T cells in tonsils. Compared with the frequencies of PD-1highCXCR5-CD4+ T cells and their IFN-γ+, IL-17A+, and IL-21+ subsets in the control inferior turbinate tissues, the frequencies of these cells and their subsets were increased in both eosinophilic and noneosinophilic NPs, whereas the frequencies of the IL-4+ and IL-4+IL-21+ subsets were increased only in eosinophilic NPs. Nasal PD-1highCXCR5-CD4+ T cells induced immunoglobulin production from B cells in a potency comparable to that induced by tonsillar follicular helper T cells. PD-1highCXCR5-CD4+ T-cell frequencies were correlated with IgE levels in eosinophilic NPs. PD-L1 and PD-L2 suppressed the function of PD-1highCXCR5-CD4+ T cells, and their levels were reduced in NPs. PD-1highCXCR5-CD4+ T-cell abundance was associated with the postsurgical relapse of NPs. CONCLUSION: PD-1highCXCR5-CD4+ T cells participate in local immunoglobulin production independent of eLTs in NPs.