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SARS-CoV-2 vaccination has been launched worldwide to build effective population-level immunity to curb the spread of this virus. The effectiveness and duration of protective immunity is a critical factor for public health. Here, we report the kinetics of the SARS-CoV-2 specific immune response in 204 individuals up to 1-year after recovery from COVID-19. RBD-IgG and full-length spike-IgG concentrations and serum neutralizing capacity decreases during the first 6-months, but is maintained stably up to 1-year after hospital discharge. Even individuals who had generated high IgG levels during early convalescent stages had IgG levels that had decreased to a similar level one year later. Notably, the RBD-IgG level positively correlates with serum neutralizing capacity, suggesting the representative role of RBD-IgG in predicting serum protection. Moreover, viral-specific cellular immune protection, including spike and nucleoprotein specific, persisted between 6 months and 12 months. Altogether, our study supports the persistence of viral-specific protective immunity over 1 year. The quality of immune response to SARS-CoV-2 is thought to wane over time, but it is unclear how long it can persist. Here the authors show persistent immune responses in a large number of patients over the course of a 1-year follow-up from the time of recovery from COVID-19.

SARS-CoV-2 variants present diverse clinical manifestations, necessitating deeper insights into their pathogenic effects. This study employs multi-omics approaches to investigate the molecular mechanisms underlying SARS-CoV-2 infection, focusing on vascular damage. Plasma proteomic analysis of unvaccinated participants infected with Omicron BA.2.76 or ancestral variants identifies key signaling pathways associated with endothelial dysfunction, with the vinculin (VCL) pathway emerging as a hallmark of Omicron infections, contributing to lung exudation. Metabolomic analysis of plasma samples from the same cohort reveals disruptions in immune function, cell membrane integrity, and metabolic processes, including altered tricarboxylic acid cycle and glycolysis pathways. An integrated analysis of proteomic and metabolomic data underscores the role of VCL in inflammation and extravasation, highlighting its interactions with adhesion molecules and inflammatory metabolites. A validation cohort of plasma samples from Omicron-infected participants confirms this association by replicating proteomic analysis, showing elevated VCL levels correlated with inflammatory markers. Functional studies in a male rat model of lung injury demonstrate that anti-VCL intervention reduces plasma VCL levels, mitigates alveolar edema, and restores alveolar-capillary barrier integrity, as assessed by histological staining and electron microscopy, thereby illustrating VCL modulation’s impact on vascular leakage and extravasation. These findings establish VCL as a potential therapeutic target for mitigating vascular complications in SARS-CoV-2 infections. Here, the authors performed plasma proteomics and metabolomics analysis and identify the vinculin (VCL) pathway as a key mediator of lung exudation in SARS-CoV-2 infections, particularly associated with Omicron infection. In a mouse model of infection inhibition of VCL leads to reduced lung pathology.

Background Acinetobacter baumannii (AB) pneumonia often leads to lung injury and multisystem dysfunction. High Mobility Group Box 1 (HMGB1) is known to play a crucial role in the progression of AB. In this study, we aimed to investigate the association between HMGB1 levels and the severity of AB pneumonia. Methods We conducted a study with a total of 91 participants, divided into three groups: patients with AB infection ( n  = 44), patients with AB complicated multiple organ disfunctions (MODs) ( n  = 19), and healthy controls ( n  = 28). Clinical parameters were assessed, HMGB1 levels were measured, and metabolomic analysis was performed. Validation experiments were conducted using SD rats. Results Patients with AB exhibited significantly elevated levels of HMGB1. In the multi-organ failure group, neutrophils, monocytes, and HMGB1 levels were higher, while lymphocytes were reduced. Metabolomic analysis revealed 28 metabolites correlated with HMGB1, among which 12-HPETE, asparagine, lactic acid, and carbamyl-aspartate showed the most notable changes. These representative metabolites reflect HMGB1-associated shifts in inflammation and energy metabolism. HMGB1 elevation was further confirmed in SD rats, and its blockade alleviated lung inflammation. Consistently, C-reactive protein (CRP) and procalcitonin (PCT) levels were also increased, supporting the link between HMGB1 and systemic inflammation. Conclusion HMGB1 levels rise sharply in AB pneumonia—especially in patients with MODs—and correlate with inflammatory and hypoxic metabolic shifts. Anti-HMGB1 treatment in SD rats reduced lung inflammation and injury, highlighting HMGB1’s potential as a diagnostic biomarker and therapeutic target.

Approximately 15–20% of COVID-19 patients will develop severe pneumonia, and about 10% of these will die if not properly managed. Earlier discrimination of potentially severe patients basing on routine clinical and laboratory changes and commencement of prophylactical management will not only save lives but also mitigate the otherwise overwhelming healthcare burden. In this retrospective investigation, the clinical and laboratory features were collected from 125 COVID-19 patients who were classified into mild (93 cases) or severe (32 cases) groups according to their clinical outcomes after 3–7 days post-admission. The subsequent analysis with single-factor and multivariate logistic regression methods indicated that 17 factors on admission differed significantly between mild and severe groups but that only comorbidity with underlying diseases, increased respiratory rate (>24/min), elevated C-reactive protein (CRP >10 mg/L), and lactate dehydrogenase (LDH >250 U/L) were independently associated with the later disease development. Finally, we evaluated their prognostic values with receiver operating characteristic curve (ROC) analysis and found that the above four factors could not confidently predict the occurrence of severe pneumonia individually, though a combination of fast respiratory rate and elevated LDH significantly increased the predictive confidence (AUC = 0.944, sensitivity = 0.941, and specificity = 0.902). A combination consisting of three or four factors could further increase the prognostic value. Additionally, measurable serum viral RNA post-admission independently predicted the severe illness occurrence. In conclusion, a combination of general clinical characteristics and laboratory tests could provide a highly confident prognostic value for identifying potentially severe COVID-19 pneumonia patients.

A novel nonlinear dynamic modeling approach is proposed for the T-shaped beam structures widely used in the field of aerospace. All of the geometrical nonlinearities including the terms in the deformation of the beams, the terms at the connections, and the free ends of beams are considered in the dynamic modeling process. The global mode method is employed to determine the natural frequencies and global mode shapes of the linearized system. The validity and accuracy of the derived model are verified by comparing the natural frequencies obtained with those calculated from FEM. Adopting the Galerkin truncation procedure, a set of reduced-order nonlinear ODEs is obtained for the structure. A study on the variation of dynamic responses taking the different numbers of global modes into account is performed to determine the number of modes taken in nonlinear vibration analysis. A comparison between the responses of the system with linear or nonlinear matching and boundary conditions is given to evaluate the importance of neglecting and reserving the nonlinear terms in matching and boundary conditions. It is shown that ignoring the nonlinear terms in both matching and boundary conditions may significantly alter the responses while developing the discretized governing ODEs of the structure.

COVID-19 continues to spread worldwide, with an increasing number of individuals experiencing reinfection after recovering from their primary infection. However, the nature and progression of this infection remain poorly understood. We aimed to investigate the immune response, severity and outcomes of Omicron BA.5 reinfection among individuals previously infected with different SARS-CoV-2 variants. We enrolled 432 COVID-19 cases who had experienced prior infection with the ancestral SARS-CoV-2 virus, Delta variant or Omicron BA.2 variant between January 2020 and May 2022 in Guangzhou, China. All cases underwent follow-up from March to April, 2023 through telephone questionnaires and clinical visits. Nasal lavage fluid and peripheral blood were collected to assess anti-RBD IgA, anti-RBD IgG and virus-specific IFN-γ secreting T cells. Our study shows that 73.1%, 56.7% and 12.5% of individuals with a prior infection of the ancestral virus, Delta or Omicron BA.2 variant experienced reinfection with the BA.5 variant, respectively. Fever, cough and sore throat were the most common symptoms of BA.5 reinfection, with most improving within one week and none progressing to a critical condition. Compared with individuals without reinfection, reinfected patients with a prior Delta infection exhibited elevated levels of nasal anti-RBD IgA, serum anti-RBD IgG and IFN-γ secreting T cells, whereas there was no noticeable change in reinfected individuals with a prior BA.2 infection. These results suggest that BA.5 reinfection is common but severe outcomes are relatively rare. Reinfection with a novel SARS-CoV-2 variant different from the prior infection may induce a more robust immune protection, which should be taken into account during vaccine development.

Ambient temperatures influence plant growth and development, however very little is known about changes in root growth in response to ambient temperature change. Here, we performed transcriptome profiling and compared the differences in gene expression at lower and higher temperatures compared with normal plant growth temperatures. Our analysis of the biological processes and molecular functions regulated by differentially expressed genes revealed that low temperature upregulated carbohydrate metabolism and transmembrane transport, and downregulated signal transduction and defense. High temperature upregulated metabolic processes, transport, and auxin biosynthesis, and downregulated catabolic processes. We found that increased temperature specifically affected the levels of Arabidopsis response regulators, ARR1 and ARR12, to decrease cytokinin signaling, altered the level of the brassinosteroid receptor BRI1 to downregulate brassinosteroid signaling, and changed the level of the gibberellin receptor DELLA to upregulate gibberellin signaling and mediate root elongation. These data contribute to our knowledge of how root growth adapts to elevated ambient temperature under climate warming.

Background Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) like semaglutide are well-used for type 2 diabetes and obesity, and recent studies show their potential renal benefits in both diabetic and non-diabetic people. However, evidence for semaglutide’s efficacy in IgAN especially in patients with obesity as a comorbidity is limited. Case presentation A 39-year-old male with a 9-month history of abnormal urine tests was admitted, diagnosed with IgAN (M1E0S0T0C0) and glomerulomegaly, and presented with obesity with BMI 34 kg/m 2 . After treatment with losartan, dapagliflozin, hydroxychloroquine, and finerenone, the 24-hour proteinuria levels decreased from 2373 mg/day to 1344 mg/day, further dropping to 702 mg/day, and then slightly increased to 920 mg/day. No significant improvement was noted half a month later, with the level remaining at 915 mg/day. We then initiated treatment with semaglutide. Following the introduction of semaglutide, a significant reduction in proteinuria was observed within four months, decreasing from 915 mg/day to 320 mg/day. Concurrently, the patient experienced a reduction in body weight, dropping from 110 kg to 95 kg over the same period. The patient's renal function remained stable throughout the follow-up, and no significant adverse drug reactions have been reported. Conclusion In this case of IgAN with obesity, adding semaglutide to standard therapy effectively reduced proteinuria and body weight, with stable renal function and good tolerability.

In this study, we evaluated the efficacy and safety of Telitacicept for treating patients with primary IgA nephropathy (IgAN) in our single hospital. We also explored the effect of Telitacicept on urinary Gd-IgA1 levels among patients with IgAN. A retrospective study was conducted. Patients were grouped according to 24-hour proteinuria (≥ 2.0 vs. < 2.0 g/day), eGFR (≥ 35 vs. < 35 mL/min/1.73 m ), gender (man vs. woman), age (≥ 35 vs. < 35 years) and therapy options (Telitacicept vs. Telitacicept plus glucocorticoid/immunosuppressor) to evaluate the therapeutic effect of Telitacicept on IgAN. We conducted a propensity score-matched comparison of the primary outcome between 20 IgAN patients with Telitacicept plus supportive treatment and 20 patients with supportive care alone. The urinary Gd-IgA1 levels were determined using ELISA. A total of 68 IgAN patients who received Telitacicept were included in this study. At baseline, the median baseline proteinuria was 1753.5 mg/day, and eGFR was 71.5 ml/min/1.73m². Significant reductions in proteinuria were observed at 1 month and sustained through 6 months of follow-up. The eGFR remained stable throughout the follow-up period. Subgroup analyses stratified by baseline proteinuria, eGFR, gender, age, and therapy options showed no significant differences in proteinuria reduction rates. Both patients initially starting Telitacicept and those who had previously failed other therapy before starting it showed significant reductions in proteinuria and stable eGFR. Importantly, we observed an improvement in the eGFR slope within the Prior Treatment plus Telitacicept Group, with the annual rate of decline slowing from 6.35 ml/min/1.73m²/year pre-treatment to 3.68 ml/min/1.73m²/year after Telitacicept therapy. Furthermore, the responsive group to Telitacicept exhibited significantly higher IgA levels compared to the non-responsive group. Compared with patients receiving supportive care alone, those who initially added Telitacicept showed a greater reduction in proteinuria by the last follow-up. Additionally, Telitacicept therapy led to a decrease in urinary Gd-IgA1/Cr levels. Telitacicept treatment was well-tolerated. In IgAN, Telitacicept demonstrated promising efficacy, significantly reducing proteinuria and stabilizing eGFR, with a favorable safety profile.