Long-term spatiotemporal variations of ammonia in the Yangtze River Delta region of China and its driving factors.

This study focuses on the spatiotemporal distribution, urban-rural variations, and driving factors of ammonia Vertical Column Densities (VCDs) in China's Yangtze River Delta region (YRD) from 2008 to 2020. Utilizing data from the Infrared Atmospheric Sounding Interferometer (IASI), Generalized Additive Models (GAM), and the GEOS-Chem chemical transport model, we observed a significant increase of NH3 VCDs in the YRD between 2014 and 2020. The spatial distribution analysis revealed higher NH3 concentrations in the northern part of the YRD region, primarily due to lower precipitation, alkaline soil, and intensive agricultural activities. NH3 VCDs in the YRD region increased significantly (65.18%) from 2008 to 2020. The highest growth rate occurs in the summer, with an annual average growth rate of 7.2% during the period from 2014 to 2020. Agricultural emissions dominated NH3 VCDs during spring and summer, with high concentrations primarily located in the agricultural areas adjacent to densely populated urban zones. Regions within several large urban areas have been discovered to exhibit relatively stable variations in NH3 VCDs. The rise in NH3 VCDs within the YRD region was primarily driven by the reduction of acidic gases like SO2, as emphasized by GAM modeling and sensitivity tests using the GEOS-Chem model. The concentration changes of acidic gases contribute to over 80% of the interannual variations in NH3 VCDs. This emphasizes the crucial role of environmental policies targeting the reduction of these acidic gases. Effective emission control is urgent to mitigate environmental hazards and secondary particulate matter, especially in the northern YRD.

Nanomaterials-based aptasensors for rapid detection and early warning of key food contaminants: A review.

The frequent occurrence of food safety incidents has aroused public concern about food safety and key contaminants. Foodborne pathogen contamination, pesticide residues, heavy metal residues, and other food safety problems will significantly impact human health. Therefore, developing efficient and sensitive detection method to ensure food safety early warning is paramount. The aptamer-based sensor (aptasensor) is a novel analytical tool with strong targeting, high sensitivity, low cost, etc. It has been extensively utilized in the pharmaceutical industry, biomedicine, environmental engineering, food safety detection, and in other diverse fields. This work reviewed the latest research progress of aptasensors for food analysis and detection, mainly introducing their application in detecting various key food contaminants. Subsequently, the sensing mechanism and performance of aptasensors are discussed. Finally, the review will examine the challenges and opportunities related to aptasensors for detecting major contaminants in food, and advance implementation of aptasensors in food safety and detection.

Enjoyment in foreign language learning: A systematic review.

In recent years, research on enjoyment in foreign language (FL) learning has flourished. To help illuminate the existing scope of inquiry and guide future research, this paper presents a systematic review of 118 empirical studies on FL learning enjoyment published between 2014 and 2023. Each study was coded according to its research context, methodological features, and research focus. The results indicate (1) a heavy focus on adult English as a foreign language (EFL) learners whose first languages are Chinese or Persian within traditional classroom learning settings; (2) a strong preference for quantitative methods; and (3) a prominent focus on enjoyment's antecedents and effects. Drawing upon these findings, we recommend that future research (1) addresses the experiences of language learners from diverse demographic backgrounds in a wider variety of learning settings; (2) applies multimodal methods to thoroughly assess the experience of enjoyment from both objective and subjective perspectives; and (3) explores the nature of enjoyable teacher-student or student-student socio-emotional interaction in greater depth.

Platelet-Rich Plasma Injection Combined With Q-Switched Ruby Laser in the Treatment of Periorbital Hyperpigmentation.

BACKGROUND: Periorbital hyperpigmentation is a prevalent skin condition that represents a large quantity of cases seen in cosmetic dermatology. Patients tend to be left with pigmentation after Q-switched ruby laser treatment, especially the perioribital area. AIMS: The study is conducted to compare the effect of PRP injection combined with laser therapy versus laser alone for periorbital hyperpigmentation treatment. PATIENTS/METHODS: In this single-center, case-control study, 30 patients with periorbital hyperpigmentation were allocated to receive PRP injection injection after Q-switched ruby laser or Q-switched ruby laser only, followed by a 12-week and 24-week follow-up visit. Visual analogue scale, Sadick tear trough rating scale, and patients' self-evaluation were used to evaluate the therapeutic effect. RESULTS: The combined group achieved a better improvement in long-term effect and had effect on facial rejuvenation. Patient satisfaction was higher in the combined group. Erythema and mild pain were the most common adverse reactions of both groups. CONCLUSIONS: Combining with PRP injection can improve the therapeutic effect of Q-switched ruby laser in treating periorbital hyperpigmentation and lessen the risk of post-inflammatory hyperpigmentation, indicating a new option for POH treatment.

Joint modeling of longitudinal health-related quality of life during concurrent chemoradiotherapy period and long-term survival among patients with advanced nasopharyngeal carcinoma.

BACKGROUND: To investigate the prognosis of longitudinal health-related quality of life (HRQOL) during concurrent chemoradiotherapy (CCRT) on survival outcomes in patients with advanced nasopharyngeal carcinoma (NPC). METHODS: During 2012-2014, 145 adult NPC patients with stage II-IVb NPC were investigated weekly using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30 (EORCT QLQ-C30) during their CCRT period. The effects of longitudinal trends of HRQOL on survival outcomes were estimated using joint modeling, and hazard ratios (HRs) with 95% confidence intervals (95% CIs) were reported as a 10-point increase in HRQOL scores. RESULTS: After a median follow-up of 83.4 months, the multivariable models showed significant associations of longitudinal increasing scores in fatigue and appetite loss during the CCRT period with distant metastasis-free survival: 10-point increases in scores of fatigue and appetite loss domains during CCRT period were significantly associated with 75% (HR: 1.75, 95% CI: 1.01, 3.02; p = 0.047) and 59% (HR: 1.59, 95% CI: 1.09, 2.59; p = 0.018) increase in the risk of distant metastasis, respectively. The prognostic effects of the longitudinal HRQOL trend on overall survival and progress-free survival were statistically non-significant. CONCLUSION: Increases in fatigue and appetite loss of HRQOL during the CCRT period are significantly associated with high risks of distant metastasis in advanced NPC patients. Nutritional support and psychological intervention are warranted for NPC patients during the treatment period.

Genome-wide association study of hypersensitivity skin reactions induced by nonionic iodinated contrast media.

BACKGROUND: In Taiwan, nonionic iodinated contrast media (ICMs) are commonly used but can occasionally cause severe side effects. The infrequency of these adverse events, coupled with the complexities in establishing direct causality, poses significant challenges for genetic research. OBJECTIVE: : To investigate the genetic factors associated with skin reactions mediated by nonionic ICMs on a genome-wide scale. METHODS: A hospital-based cohort from the China Medical University Hospital biobank was utilized to conduct a comprehensive genome-wide association study (GWAS) using PLINK v1.9. The study incorporated two distinct cohorts: one based on adverse drug reaction (ADR) reports, capturing immediate reactions, and the other based on self-reports, which primarily reflected delayed reactions. Known loci were determined by the GWAS catalog. Fine mapping was conducted by FINEMAP to predict causal variants. Pathway enrichment analysis was performed by clusterProfiler to reveal the biological function of the identified genetic signatures. RESULTS: The ADR-based cohort included 120 cases and 3640 controls. GWAS identified 6 candidate risk loci, namely rs150515068, rs6847491, rs192044153, rs191908641, rs376660317, and rs368821335. The self-report-based cohort, consisting of 275 cases and 8338 controls, revealed 36 additional candidate risk loci. Fine mapping further identified 4 causal variants within each cohort. Pathway analysis showed that immediate HSR-related genes are linked to growth hormone response and signaling, while non-immediate HSR genes are involved in neurotransmission. CONCLUSION: This study offers new perspectives on the genetic foundation of nonionic ICM-induced skin reactions within the Taiwanese population, suggesting that the genes contributing to immediate and non-immediate HSRs might have different functional roles.

A novel nonsense mutation c.747C>G in the NEUROD1 gene detected within a Chinese family affected by maturity-onset diabetes of the young type 6.

Highlights Maturity-onset diabetes of the young type 6 (MODY6) is a rare form of monogenic diabetes mellitus due to NEUROD1 gene mutation on chromosome 2q32. A 21-year-old woman exhibiting weight loss, polyuria, and hyperglycemia was initially misdiagnosed with type 1 diabetes mellitus. Considering the early-onset age, a three-generation family history of diabetes, and negative autoimmune antibodies, a MODY diagnosis was suspected. Genetic analysis revealed that she inherited a novel heterozygous nonsense NEUROD1 mutation c.747C>G (p.Tyr249*) from her father. Correct MODY6 diagnosis facilitates appropriate interventions.

Increased serum human epididymis protein 4 is associated with disease activity and systemic involvement in pediatric-onset systemic lupus erythematosus.

Objective: We aimed to investigate human epididymis protein 4 (HE4) as a potential biomarker in patients with pediatric-onset systemic lupus erythematosus (pSLE), particularly on the association of serum HE4 levels with disease activity and other laboratory tests. Methods: We included 137 patients with pSLE and 75 age- and sex-matched healthy controls (HCs). Serum HE4 level was measured by a chemiluminescent microparticle on an Abbott ARCHITECT i2000SR Immunoassay Analyzer. Comparisons between groups were performed using the independent Student t-test, Mann-Whitney U test, Chi-square test, or Fisher's exact test, as appropriate. We also determined the relationships between HE4 and clinical parameters and evaluated disease activity using SLE Disease Activity Index (SLEDAI) and renal SLEDAI (rSLEDAI). Results: Serum HE4 levels in patients with pSLE (44.6 pmol/L; IQR, 32.5-73.5) were significantly higher than those in HCs (38.9 pmol/L; IQR, 34-46.1). HE4 levels were significantly higher in moderate to severe disease activities (57.4 pmol/L, IQR 37.7-164.5) than in mild disease activities (38.8 pmol/L, IQR 30.1-48.5) or HCs (38.9 pmol/L, IQR 34.0-46.1), as well as in active renal disease activities (77.2 pmol/L, IQR 47.4-224.1) than in inactive renal disease activities (36.1 pmol/L, IQR 27.8-46.7). The ROC curve analysis showed that HE4 could discriminate pSLE with renal (AUC, 0.717; 95% CI, 0.632-0.801), hematological (AUC, 0.740; 95% CI, 0.648-0.831), and cardiovascular involvement (AUC:0.775, 95% CI 0.669-0.880). Serum HE4 levels significantly correlated with several indicators related to renal morbidity, such as creatinine, blood urea nitrogen, uric acid, cystatin C, urine protein/24 h, etc. Conclusion: Serum HE4 levels in pSLE were elevated and highly associated with disease activity and systemic involvement, indicating HE4 as a potential biomarker for pSLE.

Aptasensors application for cow's milk allergens detection and early warning: Progress, challenge, and perspective.

Cow's milk allergy (CMA) is considered one of the most prevalent food allergies and a public health concern. Modern medical research shows that the effective way to prevent allergic reactions is to prevent allergic patients from consuming allergenic substances. Therefore, the development of rapid and accurate detection technology for milk allergens detection and early warning is critical to safeguarding those with a cow milk allergy. As the oligonucleotide sequences with high specificity and selectivity, aptamers frequently assemble with transduction elements forming multifarious aptasensors for quantitative detection owing to their high-affinity binding to the target. Current aptasensors in the field of cow's milk allergen detection in recent years are explored in this review. This review takes a look back at a few common assays, including ELISA and PCR, before presenting a clear overview of the aptamer and threshold doses. It delves into a detailed discussion of the current aptamer-based detection techniques and related theories for milk allergen identification. Last but not least, we conclude with a discussion and outlook of the advancements made in allergen detection with aptamers. We sincerely hope that there will be more extensive applications for aptasensors in the future contributing to reducing the possibility of patients suffering from adverse reactions.

ZnS Nanoseeds Sealed in N, P, S Co-Doped Carbon Hollow Rhombic Dodecahedra as a Superlithiophilic Host for Dendrite-Free Lithium Metal Anodes.

Lithium (Li) metal is considered a hopeful anode for next-generation Li-ion batteries thanks to its ultra-high theoretical specific capacity, extra-low theoretical density, and low negative potential. However, the uncontrolled growth of Li dendrites and volume fluctuation during plating/stripping processes severely hamper its commercial application. Herein, ZnS seeds sealed in N, P, S co-doped carbon hollow rhombic dodecahedra (ZnS@NPS-C HRD) is fabricated as a superlithiophilic host for Li metal anodes (LMAs) to solve the above problems. In addition, the Li nucleation and deposition mechanism on ZnS@NPS-C HRD is investigated by in situ optical microscopy, ex-situ X-ray diffraction, scanning electron microscopy, and theoretical calculations. Owing to the synergistic strategy of ZnS seeds-inducing nucleation and Li-limited growth, the as-prepared composite exhibits stability for 300 cycles in asymmetric cells and a long lifespan over 1100 h in symmetric cells. Moreover, the ZnS@NPS-C HRD@Li|LiFePO4 full cell demonstrates a reversible capacity of 100.91 mAh g-1 after 400 cycles at 1 C.

Triboelectric Nanogenerator Made with Stretchable, Antibacterial Hydrogel Electrodes for Biomechanical Sensing.

Triboelectric nanogenerators (TENGs) have attracted widespread attention as a promising candidate for energy harvesting due to their flexibility and high power density. To meet diverse application scenarios, a highly stretchable (349%), conductive (1.87 S m-1), and antibacterial electrode composed of carbon quantum dots/LiCl/agar-polyacrylamide (CQDs/LiCl/agar-PAAm) dual-network (DN) hydrogel is developed for wearable TENGs. Notably, the concentration of agar alters the pore spacing and pore size of the DN hydrogel, thereby impacting the network cross-linking density and the migration of conductive ions (Li+ and Cl-). This variation further affects the mechanical strength and conductivity of the hydrogel electrode, thus modulating the mechanical stability and electrical output performance of the TENGs. With the optimal agar content, the tensile strength and conductivity of the hydrogel electrode increase by 211 and 719%, respectively. This enhancement ensures the stable output of TENGs during continuous operation (6000 cycles), with open-circuit voltage, short-circuit current, and transferred charge increasing by 200, 530, and 155%, respectively. Additionally, doping with CQDs enables the hydrogel electrode to effectively inhibit the Gram-negative bacterium Escherichia coli. Finally, the TENGs are utilized as a self-power smart ring for efficient and concise information transmission via Morse code. Consequently, this study introduces a creative approach for designing and implementing multifunctional, flexible wearable devices.

ER membrane remodeling by targeting RTN4 induces pyroptosis to facilitate antitumor immune.

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to PKM2-dependent conventional caspase-3/GSDME cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-PD-1. In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.

Visible-light-prompted photoelectrochemical sensors fabricated using Er3NbO7/P@g-C3N4/SnS2 nanocomposite for detecting mercury ion in environmental water samples.

Photoelectrochemical (PEC) detection technology is key for fighting pollution, leveraging the photoelectric conversion of the photoelectrode material. A specialized photoelectrode was developed to detect Hg2+ ions with exceptional sensitivity, utilizing an anodic PEC sensor composed of Er3NbO7/P@g-C3N4/SnS2 ternary nanocomposite. Rare earth metal niobates (RENs) were chosen due to their underexplored potential, whose performance was enhanced through bandgap engineering and surface modification, facilitated by P@g-C3N4 as an immobilization matrix and SnS2, belonging to the I-IV semiconductors category fostering hybrid heterojunction formation for boasting optical properties and suitable redox potentials. Introducing Hg2+ into the system, a specific amalgamation reaction occurs between reduced Hg and Sn. This reaction obstructs electron transfer to the FTO electrode surface, leading to the recombination of charges. The proposed PEC sensor exhibited remarkable analytical performance for Hg2+ detection, high sensitivity, a detection limit of 0.019 pM, excellent selectivity, and a detectable concentration range of 0.002-0.15 nM. Additionally, it demonstrated good recovery and low relative standard deviation when analyzing Hg2+ in water samples, highlighting the potential application of the heterostructure in detecting heavy metal ions via PEC technology.

Evaluation of the Psychometric Properties of the Translated Physical Self-Perception Profile among Chinese Breast Cancer Survivor.

PURPOSE: To translate the original English version of Physical Self-Perception Profile into Cantonese Chinese, while considering linguistic and socio-cultural characteristics, and evaluate its psychometric properties among Chinese breast cancer survivors in Hong Kong, China, thus providing a valid, culturally relevant tool for assessing of the physical self-esteem among this population. METHODS: The 30-item Physical Self-Perception Profile was translated into Chinese by the combined translation technique. The psychometric properties of the Cantonese version of the Physical Self-Perception Profile were examined in 292 Hong Kong Chinese breast cancer survivors for internal consistency and test-retest reliability. A confirmatory factor analysis was conducted to evaluate the structural validity. A panel of 5 experts examined its content validity. The concurrent validity was examined by correlating the Physical Self-Perception Profile and a validated global self-esteem measure. RESULTS: The Cantonese version of the Physical Self-Perception Profile demonstrated satisfactory content validity, also satisfactory internal consistency with Cronbach's α ranging from 0.64 to 0.80, as well as good test-retest reliability, with an intra-class correlation coefficient ranging from 0.77 to 0.81. The confirmatory factor analysis showed a fairly good fit of the four-factor subdomain structure, namely, physical condition, physical strength, body attractiveness and sports competence. The concurrent validity of the Chinese-version Physical Self-Perception Profile was demonstrated by a significant positive correlation between the physical self-worth domain and four subdomains with global self-esteem. In addition, the four subdomains had statistically significant positive correlations with the physical self-worth domain indicating the instrument's hierarchical structure. CONCLUSIONS: The study translated the Physical Self-Perception Profile from English to Cantonese and demonstrated its desirable psychometric properties among Chinese Hong Kong breast cancer survivors. The linguistical and cultural adaptation of this instrument can serve as a valid and reliable tool for assessing physical self-esteem among breast cancer survivors in Hong Kong, China.

Astragaloside IV suppresses the proliferation and inflammatory response of human epidermal keratinocytes and ameliorates imiquimod-induced psoriasis-like skin damage in mice.

The primary pathological features of psoriasis include excessive epidermal keratinocytes and infiltration of inflammatory cells, which are pivotal targets for psoriasis therapy. Astragaloside IV (AS-IV), the principal active compound of astragalus, exhibits anti-inflammatory, antioxidant, and immune-modulatory properties. This study aims to investigate AS-IV's anti--psoriatic effects and underlying mechanisms. Normal human epidermal keratinocytes (NHEKs) were stimulated with a combination of TNF-α, IL-17A, IL-1α, IL-22, and oncostatin M (M5) to replicate psoriatic keratinocyte pathology in vitro. Cell proliferation was assessed using CCK8 and EDU staining. Pro-inflammatory cytokine levels were measured via qRT-PCR. In addition, an imiquimod (IMQ)-induced psoriasis mouse model was utilized. Skin histology changes were evaluated with HE staining, while IL-6 and TNF-α levels in mouse serum were quantified using ELISA. NF-κB pathway protein expression was analyzed by western blotting. The results demonstrated that AS-IV inhibited M5-induced proliferation of NHEKs. AS-IV reduced M5-stimulated IL-1ß, IL-6, IL-8, TNF-α, IL-23, and MCP-1 expression in NHEKs. Moreover, M5-induced phosphorylation of IκBα and p65 was significantly attenuated by AS-IV. Furthermore, AS-IV application ameliorated erythema, scale formation, and epidermal thickening in IMQ-induced psoriasis-like mouse models. AS-IV also decreased IL-6 and TNF-α levels in mouse serum and inhibited IκBα and p65 phosphorylation in skin tissues. However, prostratin treatment reversed these effects. These findings underscore AS-IV's capacity to mitigate M5-induced NHEK proliferation and inflammation. AS-IV shows promise in alleviating IMQ-induced psoriasis-like skin lesions and inflammation by suppressing the NF-κB pathway.

CYR61/CCN1: A novel mediator of redox response in corneal stromal cells of keratoconus.

Keratoconus (KC) is a progressive, multifactorial and ectatic corneal disorder that characterized by steepening thinning of the cornea. It was previously demonstrated that oxidative stress has a strong link with KC progression. However, the molecular mechanism underlying oxidative stress response in KC remains unclear. Hence, the present study analyzed the heterogeneity of response of corneal stromal cells (CSCs) to oxidative stress in order to further illustrate how oxidative shape the pathophysiology of KC. Single-cell transcriptomics analysis revealed that CSCs demonstrated significant higher oxidative stress score in the KC group compared to the Ctrl group. The expression of oxidative markers verified by experiments illustrated elevated oxidative stress levels and insufficient antioxidant levels in CSCs of KC. In further single-cell transcriptomics analysis, we identified CYR61 to distinguish different subgroups of CSCs responding to oxidative stress. The cornea stroma cells in KC could be differentiated into CYR61high cells and CYR61low cells. Of note, the CYR61high cells showed lower score in collagen production process and higher score in collagen catabolic process. Further experiments illustrated that CYR61 was elevated in KC and associated with collagen production.

Establishment of cutoff values for anti-ß2 glycoprotein I antibodies in women of reproductive age in Southwest China.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by vascular thrombosis and obstetric morbidity, with accurate laboratory examination of antiphospholipid antibodies (aPLs) being crucial for diagnosis. This study focused on anti-ß2 glycoprotein I (aß2GPI) antibodies and aimed to establish the first population-based cutoff values for aß2GPI IgA/IgM/IgG antibodies in non-pregnant women of reproductive age in Southwest China. The study cohort comprised 181 healthy women of reproductive age for study. Blood samples were collected on an early morning fast. Anti-ß2GPI antibodies including IgA, IgM and IgG were measured in serum using the HOB® BioCLIA kit. According to the Clinical and Laboratory Standards Institute (CLSI) guidelines, the study used non-parametric percentile methods to calculate the 95th, 97.5th, and 99th percentiles cutoff values for aß2GPI IgA/IgM/IgG antibodies, along with corresponding 90% confidence intervals (CI), while excluding outliers. A total of 168 independent samples were collected for verification, including 85 samples from healthy subjects and 83 samples from APS patients, in order to evaluate the analytical performance of the obtained cutoff values. The 99th percentile cutoff values were 3.36 RU/mL for aß2GPI IgA, 27.54 RU/mL for aß2GPI IgM and 1.81 RU/mL for aß2GPI IgG, which indicated that the levels of aß2GPI IgM antibodies were generally higher compared to those of IgA and IgG antibodies. Our established reference range was confirmed to be successful in validating the detected values of aß2GPI antibodies in all healthy controls. With the 99th percentile cutoff value, the sensitivity was 14.46% for aß2GPI IgA, 22.89% for aß2GPI IgG, and 9.64% for aß2GPI IgM in APS patients. This study established population-based cutoff values that are applicable to the local population for the accurate laboratory examination of aß2GPI antibodies in non-pregnant women of reproductive age. The study also recommends paying more attention to IgM positivity in women of reproductive age.

New-onset obstructive airway disease following COVID-19: a multicenter retrospective cohort study.

BACKGROUND: The study assessed the association between COVID-19 and new-onset obstructive airway diseases, including asthma, chronic obstructive pulmonary disease, and bronchiectasis among vaccinated individuals recovering from COVID-19 during the Omicron wave. METHODS: This multicenter retrospective cohort study comprised 549,606 individuals from the U.S. Collaborative Network of TriNetX database, from January 8, 2022, to January 17, 2024. The hazard of new-onset obstructive airway diseases between COVID-19 and no-COVID-19 groups were compared following propensity score matching using the Kaplan-Meier method and Cox proportional hazards model. RESULTS: After propensity score matching, each group contained 274,803 participants. Patients with COVID-19 exhibited a higher risk of developing new-onset asthma than that of individuals without COVID-19 (adjusted hazard ratio (aHR), 1.27; 95% CI, 1.22-1.33; p < 0.001). Stratified analyses by age, SARS-CoV-2 variant, vaccination status, and infection status consistently supported this association. Non-hospitalized individuals with COVID-19 demonstrated a higher risk of new-onset asthma (aHR, 1.27; 95% CI, 1.22-1.33; p < 0.001); however, no significant differences were observed in hospitalized and critically ill groups. The study also identified an increased risk of subsequent bronchiectasis following COVID-19 (aHR, 1.30; 95% CI, 1.13-1.50; p < 0.001). In contrast, there was no significant difference in the hazard of chronic obstructive pulmonary disease between the groups (aHR, 1.00; 95% CI, 0.95-1.06; p = 0.994). CONCLUSION: This study offers convincing evidence of the association between COVID-19 and the subsequent onset of asthma and bronchiectasis. It underscores the need for a multidisciplinary approach to post-COVID-19 care, with a particular focus on respiratory health.

The preventive effect of inhaled antibiotic against ventilator-associated pneumonia: a systematic review and meta-analysis.

BACKGROUND: Ventilator-associated pneumonia (VAP) constitutes a considerable challenge for patients in intensive care units (ICUs) and necessitates the development of effective preventive strategies. This study aimed to evaluate the clinical efficacy of inhaled antibiotics for preventing VAP. METHODS: PubMed, Embase, and ClinicalTrials.gov were searched until January 21, 2024. Randomized controlled trials (RCTs) investigating the clinical efficacy of inhaled antibiotics for VAP prevention were included. RESULTS: Seven RCTs, involving 1465 patients, of whom 734 were classified as the study group receiving inhaled antibiotics and 731 as the control group receiving placebo were included in this meta-analysis. Overall, the occurrence of VAP was significantly lower in the study group than in the control group (risk ratio [RR], 0.69; 95% confidence interval [CI], 0.51 to 0.92). However, there were no significant differences in mortality (RR, 0.90; 95% CI, 0.74 to 1.09), length of stay in ICU (mean difference [MD], 0.10 days; 95% CI, -0.91 to 1.1) and hospital (MD, 0.30 days; 95% CI, -1.82 to 2.43), and mechanical ventilation (MV) duration (MD, 0.45 days; 95% CI, -0.45 to 1.35) between groups. CONCLUSION: Inhaled antibiotics hold promise for mitigating the risk of VAP among critically ill patients. However, their impact on mortality, length of stay in ICU and hospital, and MV duration was not statistically significant.

Amlexanox targeted inhibition of TBK1 regulates immune cell function to exacerbate DSS-induced inflammatory bowel disease.

Amlexanox (ALX) is a small molecule drug for the treatment of inflammatory, autoimmune, metabolic and tumor diseases. At present, there are no studies on whether ALX has a therapeutic effect on inflammatory bowel disease (IBD). In this study, we used a mouse model of dextran sulfate sodium (DSS)-induced colitis to investigate the effect of ALX targeted inhibition of TBK1 on colitis. We found that the severity of colitis in mice was correlated with TBK1 expression. Notably, although ALX inhibited the activation of the TBK1-NF-κB/TBK1-IRF3 pro-inflammatory signaling pathway, it exacerbated colitis and reduced survival in mice. The results of drug safety experiments ruled out a relationship between this exacerbating effect and drug toxicity. In addition, ELISA results showed that ALX promoted the secretion of IL-1ß and IFN-α, and inhibited the production of cytokines IL-6, TNF-α, IL-10, TGF-ß and secretory IgA. Flow cytometry results further showed that ALX promoted T cell proliferation, activation and differentiation, and thus played a pro-inflammatory role; Also, ALX inhibited the generation of dendritic cells and the polarization of macrophages to M1 type, thus exerting anti-inflammatory effect. These data suggest that the regulation of ALX on the function of different immune cells is different, so the effect on the inflammatory response is bidirectional. In conclusion, our study demonstrates that simply inhibiting TBK1 in all immune cells is not effective for the treatment of colitis. Further investigation the anti-inflammatory mechanism of ALX on dendritic cells and macrophages may provide a new strategy for the treatment of IBD.