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Abstract Background Animal and human health are seriously threatened by bacterial infections, which can lead to bacteremia and extremely high rates of morbidity and mortality. Recently, there have been reports indicating the involvement of exosomal circular RNAs (circRNAs) in a range of human disorders and tumor types. However, the role of exosomal circRNAs in bacterial infection remains elusive. Methods We extracted and identified exosomes from the culture medium of PIEC cells infected with or without Glaesserella parasuis. RNA sequencing analysis was performed on the exosomes to screen and identify circRNAs (circHIF1α) associated with Glaesserella parasuis infection. PIEC cells were infected with Staphylococcus aureus or Streptococcus suis 2 to further determine whether exosome-derived circHIF1α was the crucial circHIF1α associated with bacterial infections. The transmission process of exosomes and their circHIF1α between cells was clarified via exosome tracing and co-culture assay. Moreover, the mechanism of circHIF1α being packaged into exosomes was explored, and the effects of exosomes and their circHIF1α on cell proliferation, DNA damage and cell cycle were analyzed. In addition, the binding mode and site of interacting proteins with circHIF1α were further determined. In vivo and in vitro, the role of exosomes and their circHIF1α in host resistance to bacterial infection was confirmed. Results We first discovered a new circHIF1α that was very stable and detectable, encapsulated into exosomes by hnRNPA2B1, and whose expression in exosomes of bacterially infected PIEC cells significantly decreased. Additionally, exosomal circHIF1α reduced bacterial infection both in vitro and in vivo and suppressed the growth of reception cells. Mechanistically, the circHIF1α interacted with the KH domain of IGF2BP3 in an m6A-modified manner, which mediated DNA damage to arrest the cells at the G1/S phase through the interaction between the regulator of Chromosome Condensation 2 (RCC2) and γ-H2AX protein. Exosomal circHIF1α is a unique therapeutic target for bacterial infection since this work highlights its critical function in fighting bacterial infection.

ObjectiveThe role of adiponectin (APN) in regulating inflammation is well recognized in metabolic disease, but the dysregulation of APN in lower respiratory tract infection (LRTI) remains controversial. We aimed to measure APN and its signaling receptors, adiponectin receptor (AdipoR), in peripheral blood mononuclear cells (PBMCs) from LRTI patients to explore their potential roles in the LRTI process.MethodsA total of 99 LRTI patients from the Second Xiangya Hospital of Central South University were categorized into acute (n=35) and non-acute (n=64), and non-severe (n=62) and severe (n=37) groups. Serum APN was quantified using ELISA, and mRNA levels of PBMC AdipoRs were determined by RT-qPCR.ResultsBoth levels of APN in circulation and AdipoR1 mRNA were significantly elevated in the LRTI patients (P=2.61E-04; P=2.49E-08), while no statistical difference was observed for AdipoR2. APN levels were increased in the non-acute group compared to the acute group (P=6.06E-04) and AdipoR1 levels were higher in the severe group (P=0.004). Increased APN and AdipoR1 mRNA levels were positively associated with LRTI even after adjustment for sex, age, BMI and blood lipids (OR=1.10; 95% CI 1.04-1.18; P=9.61E-04; OR=2.69; 95% CI 1.29-5.58; P=0.008). Subgroup analyses based on sex, age, and BMI revealed APN elevation in males, ≥65-year-olds, and overweight individuals, with higher AdipoR2 mRNA in females and those under 65; AdipoR1 was uniformly elevated. Additionally, APN was negatively correlated with lymphocyte count in acute and severe subgroup; AdipoR1 was positively correlated with indicators of inflammation in LRTI group.ConclusionOur study highlights that serum APN and AdipoR1 mRNA in PBMCs are associated with LRTI. Circulating APN and PBMC AdipoR1 have different significances in LRTI acute onset and severity.

ABSTRACT Background Systemic inflammation stands as a pivotal factor tightly interwoven with the progression of COVID‐19. This study endeavors to elucidate the significance of three key inflammatory molecules, that is, heparin‐binding protein (HBP), interleukin‐6 (IL‐6), and C‐reactive protein (CRP), in assessing the severity and prognostic implications of COVID‐19. Methods The demographic, clinical, and laboratory data were retrospectively collected from a cohort of 214 adult patients diagnosed with COVID‐19. Patients were divided into two groups: nonsevere (n = 93; 43.5%) and severe (n = 121; 56.5%). Additionally, based on their organ function, patients were categorized into nonorgan failure (n = 137) and organ failure (n = 77) groups. The levels of inflammation‐related cytokines were then compared among these defined groups. Results The severe group was characterized by a higher proportion of males, older age, and longer hospital stays compared to nonsevere cases. Additionally, severe cases exhibited a higher prevalence of underlying diseases and organ failure. Statistical analysis revealed significantly elevated levels of HBP, IL‐6, and CRP in the severe group. HBP, IL‐6, and CRP were identified as independent risk factors for severe COVID‐19. Furthermore, a combined assessment of these biomarkers demonstrated superior diagnostic sensitivity (85.10%) and specificity (95.70%) for predicting COVID‐19 severity. A positive relationship between elevated HBP, IL‐6, and CRP levels and impaired organ function was also observed. The predictive efficiency significantly increased (hazard ratio = 3.631, log‐rank p = 0.003) when two or more of them were combinedly used. Notably, elevated levels of HBP, IL‐6, and CRP were associated with an increased risk of mortality. Conclusions In conclusion, the combined assessment of HBP, IL‐6, and CRP offers enhanced accuracy and specificity in predicting the severity, organ failure, and mortality risk associated with COVID‐19.

Insulin resistance (IR) is the main cause of type 2 diabetes mellitus (T2DM). The specific targets and underlying mechanisms responsible for the ameliorative effects of the stilbenoid compounds found in fenugreek seeds for ameliorating IR require further study. Here, we were predicted by using the network pharmacology prediction, molecular docking and molecular dynamics simulation approach the targets in common and the potential mechanismsof three stilbenoid compounds (rhaponticin, desoxyrhaponticin, and rhapontigenin) in relation to T2DM and IR. The results showed that the compounds may improve IR through the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway. Molecular docking studies revealed that they exhibit high binding affinity with the structural domains of peroxisome proliferator-activated receptor gamma (PPARG), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), PI3K, and AKT. These results suggest that PPARG and GAPDH may be the potential targets for these three compounds in the treatment of T2DM.Subsequently, experiments using the zebrafish T2DM model showed that the stilbenoid compounds had varying degrees of efficacy in improving IR through the PI3K/AKT/mTOR signaling pathway, and rhaponticin had the most promising effects. The findings implicate a potential mechanism of action for the three stilbenoid compounds in enhancing insulin resistance (IR) through modulation of the PI3K/AKT/mTOR pathway.

Background: During the COVID-19 pandemic, three different types of inactivated SARS-CoV-2 vaccines, namely BBIBP-CorV, WIBP-CorV and CoronaVac, were manufactured and used for vaccination in China. However, as far as we know, no comparison of their induced serum neutralization has been carried out so far, possibly due to the regional difference in vaccine distribution, the difficulty in undertaking a comprehensive evaluation, and the intention to avoid unnecessary bias in populations for a certain type of inactivated vaccine.Methods: Since all three of these inactivated vaccines are no longer produced and used for vaccination, here, we retrospectively compared the serum neutralizing activities induced by these three different types of inactivated SARS-CoV-2 vaccines. Results: Compared with unvaccinated uninfected control donors, primary inactivated vaccination (232 donors) induced increased serum neutralizing titers against wildtype SARS-CoV-2 in around 70% of donors during the first 100 days. However, the neutralization effect waned quickly after 100 days, and significantly diminished against Delta and Omicron (B.1.1.529) variants. Moreover, the newly emerged Omicron variants, such as BA.2.75, BA.4/5, BF.7, BQ.1.1, and XBB, almost fully evaded the induced serum neutralization activity. Conclusions: These three distinct types of inactivated vaccines, namely BBIBP-CorV, WIBP-CorV, and CoronaVac, induced serum neutralization in most vaccinated populations but in a short-term and variant-evaded manner with no significant difference among these inactivated vaccines.

Abstract Background After the eradication of smallpox in China in 1979, vaccination with the vaccinia virus (VACV) Tiantan strain for the general population was stopped in 1980. As the monkeypox virus (MPXV) is rapidly spreading in the world, we would like to investigate whether the individuals with historic VACV Tiantan strain vaccination, even after more than 40 years, could still provide ELISA reactivity and neutralizing protection; and whether the unvaccinated individuals have no antibody reactivity against MPXV at all. Results We established serologic ELISA to measure the serum anti-MPXV titer by using immunodominant MPXV surface proteins, A35R, B6R, A29L, and M1R. A small proportion of individuals (born before 1980) with historic VACV Tiantan strain vaccination exhibited serum ELISA cross-reactivity against these MPXV surface proteins. Consistently, these donors also showed ELISA seropositivity and serum neutralization against VACV Tiantan strain. However, surprisingly, some unvaccinated young adults (born after 1980) also showed potent serum ELISA activity against MPXV proteins, possibly due to their past infection by some self-limiting Orthopoxvirus (OPXV). Conclusions We report the serum ELISA cross-reactivity against MPXV surface protein in a small proportion of individuals both with and without VACV Tiantan strain vaccination history. Combined with our serum neutralization assay against VACV and the recent literature about mice vaccinated with VACV Tiantan strain, our study confirmed the anti-MPXV cross-reactivity and cross-neutralization of smallpox vaccine using VACV Tiantan strain. Therefore, it is necessary to restart the smallpox vaccination program in high risk populations.

Abstract Background Angiosarcoma of the breast is a rare malignancy. There are little data evaluating the survival and estimating the prognostic factors. The best surgical management and the role of systemic adjuvant therapy remain ill‐defined. This study aimed to investigate the clinicopathological features, survival, and prognostic factors of breast angiosarcoma. Methods The data on patients diagnosed with breast angiosarcoma were extracted from the Surveillance, Epidemiology, and End Results database (1975–2016). Univariate and multivariate Cox regression analyses were used to estimate the influential prognostic factors. The overall survival (OS) and disease‐specific survival (DSS) of patients with breast angiosarcoma were evaluated. Results This study included 656 patients diagnosed with breast angiosarcoma between 1975 and 2016. The 5‐year OS rate of all patients was 44.9% (95% CI 40.8–49.0). In both OS and DSS, Kaplan–Meier survival analyses revealed significant differences for both OS and DSS according to age, year at diagnosis, laterality, grade, and stage (all log‐rank p

The Clostridium perfringens epidemic threatens biosecurity and causes significant economic losses. C. perfringens infections are linked to more than one hundred million cases of food poisoning annually, and 8–60% of susceptible animals are vulnerable to infection, resulting in an economic loss of more than 6 hundred million USD. The enzymes and toxins (>20 species) produced by C. perfringens play a role in intestinal colonization, immunological evasion, intestinal micro-ecosystem imbalance, and intestinal mucosal disruption, all influencing host health. In recent decades, there has been an increase in drug resistance in C. perfringens due to antibiotic misuse and bacterial evolution. At the same time, traditional control interventions have proven ineffective, highlighting the urgent need to develop and implement new strategies and approaches to improve intervention targeting. Therefore, an in-depth understanding of the spatial and temporal evolutionary characteristics, transmission routes, colonization dynamics, and pathogenic mechanisms of C. perfringens will aid in the development of optimal therapeutic strategies and vaccines for C. perfringens management. Here, we review the global epidemiology of C. perfringens, as well as the molecular features and roles of various virulence factors in C. perfringens pathogenicity. In addition, we emphasize measures to prevent and control this zoonotic disease to reduce the transmission and infection of C. perfringens.

Summary: Striking antibody evasion by emerging circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants drives the identification of broadly neutralizing antibodies (bNAbs). However, how a bNAb acquires increased neutralization breadth during antibody evolution is still elusive. Here, we identify a clonally related antibody family from a convalescent individual. One of the members, XG005, exhibits potent and broad neutralizing activities against SARS-CoV-2 variants, while the other members show significant reductions in neutralization breadth and potency, especially against the Omicron sublineages. Structural analysis visualizing the XG005-Omicron spike binding interface reveals how crucial somatic mutations endow XG005 with greater neutralization potency and breadth. A single administration of XG005 with extended half-life, reduced antibody-dependent enhancement (ADE) effect, and increased antibody product quality exhibits a high therapeutic efficacy in BA.2- and BA.5-challenged mice. Our results provide a natural example to show the importance of somatic hypermutation during antibody evolution for SARS-CoV-2 neutralization breadth and potency.

Objectives Fatigue is common in patients with chronic liver disease; however, its pathogenesis is unclear. This study aimed to provide insights into the pathogenesis of chronic liver disease-related fatigue by assessing the relationship between fatigue and the degree of inflammation in chronic liver disease.Design We performed a cross-sectional study of 1374 patients with pathologically proven chronic liver disease diagnosed at the Affiliated Hospital of Hangzhou Normal University in Hangzhou, China.Setting Primary single-centre study.Participants One thousand three hundred and seventy-four patients with liver biopsy-proven chronic liver disease.Interventions The patients were divided into fatigue and non-fatigue groups according to the Chronic Liver Disease Questionnaire. Propensity score matching was used to match the baseline features of the patients in the two groups.Primary and secondary outcome measures Liver steatosis, ballooning, inflammation and fibrosis were measured according to the pathological results of liver biopsy. Fatigue was measured using the Chronic Liver Disease Questionnaire.Results Of the 1374 patients, 262 (19.67%) experienced fatigue. There were 242 and 484 patients with and without fatigue, respectively, who were successfully matched for sex, age and classification of chronic liver disease by propensity score matching. After matching, the fatigue group showed higher liver enzyme levels, inflammation grades and fibrosis stages than the non-fatigue group (p0.05).Conclusion Patients with chronic liver disease were burdened by fatigue, which increased progressively with rising liver inflammation severity in young-aged and middle-aged rather than elderly patients.

The invention of printing technologies has revolutionized the manner in which information is transmitted and reproduced. In the modern era, printing technologies , which are equipped with computerized control and design methods, have become considerably efficient and effective, facilitating A significant breakthrough in the manufacture of high-performance electrochemical energy storage systems. Through careful design and execution, the components of energy storage devices, particularly electrodes, can be formulated into functional inks, enabling the use of divers materials and devices in high-performance energy storage applications. This reviewfocuses on three major printing technologies: inkjet printing, screen printing, and 3D printing, introducing the principles of each printing technology, the design and preparation of various electrode inks, and their applications in supercapacitors. Finally, the challenges and scope for the future development of printing technologies forhigh-performance supercapacitors are presented.

Background. The inflammatory response is an important part of the pathogenesis of acne vulgaris. Auriculotherapy has been shown to have a good therapeutic effect on this disease. The aim of this study was to explore the mechanism underlying the anti-inflammatory effect of auriculotherapy in the treatment of acne vulgaris. Methods. Propionibacterium acnes was injected subcutaneously into the ears of rats to establish an animal model of acne. The auriculotherapy intervention in rats consisted of auricular bloodletting therapy (ABT), auricular point sticking (APS), or a combination of both (ABPS). The anti-inflammatory effects of auriculotherapy were evaluated by measuring changes in ear thickness, local body surface microcirculation in the ear, and serum inflammatory factors in rats. The polarization of macrophages was analyzed by flow cytometry, and the expression of TLR2/NF-κB signaling pathway in the target tissues was analyzed using western blot. Results. ABT, APS, and ABPS all reduced the erythema of ear acne, decreased microcirculation in localized ear acne, and decreased serum levels of TNF-α and IL-1β in rats. Meanwhile, the three interventions reduced M1-type macrophages and increased M2-type macrophages; only APS could reduce the expression of TLR2/NF-κB signaling pathway. Conclusion. ABT, APS, and ABPS can improve the inflammatory symptoms of acne and reduce inflammatory cytokines. APS may exert anti-inflammatory effects by altering macrophage polarization and decreasing TLR2/NF-κB expression.

High‐dimensional analyses of tissue samples from patients with rheumatic diseases are providing increasingly detailed descriptions of the immune cell populations that infiltrate tissues in different rheumatic diseases. Here we review key observations emerging from high‐dimensional analyses of T cells within tissues in different rheumatic diseases, highlighting common themes across diseases as well as distinguishing features. Single‐cell RNA sequencing analyses capture several dimensions of T‐cell states, yet surprisingly, these analyses generally have not demonstrated distinct clusters of paradigmatic T‐cell effector subsets, such as T helper (Th) 1, Th2, and Th17 cells. Rather, global transcriptomics robustly identify both proliferating T cells and regulatory T cells and have also helped to reveal new effector subsets in inflamed tissues, including T peripheral helper cells and granzyme K+ T cells. Further characterization of the T‐cell populations that accumulate within target tissues should enable more precise targeting of biologic therapies and accelerate development of more specific biomarkers to track activity of relevant immune pathways in patients with rheumatic diseases.

A patient with pneumonia had a fever for 2 weeks. After the initial anti-infection treatment failed, he was diagnosed with C. psittaci pneumonia complicated with organizing pneumonia, through next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) and lung biopsy. He was treated with antibiotics and corticosteroids for 2 months.

Glaesserella parasuis (G. parasuis), an important pathogenic bacterium, cause Glässer’s disease, and has resulted in tremendous economic losses to the global swine industry. G. parasuis infection causes typical acute systemic inflammation. However, the molecular details of how the host modulates the acute inflammatory response induced by G. parasuis are largely unknown. In this study, we found that G. parasuis LZ and LPS both enhanced the mortality of PAM cells, and at the same time, the level of ATP was enhanced. LPS treatment significantly increased the expressions of IL-1β, P2X7R, NLRP3, NF-κB, p-NF-κB, and GSDMD, leading to pyroptosis. Furthermore, these proteins’ expression was enhanced following extracellular ATP further stimulation. When reduced the production of P2X7R, NF-κB-NLRP3-GSDMS inflammasome signaling pathway was inhibited, and the mortality of cells was reduced. MCC950 treatment repressed the formation of inflammasome and reduced mortality. Further exploration found that the knockdown of TLR4 significantly reduced ATP content and cell mortality, and inhibited the expression of p-NF-κB and NLRP3. These findings suggested upregulation of TLR4-dependent ATP production is critical for G. parasuis LPS-mediated inflammation, provided new insights into the molecular pathways underlying the inflammatory response induced by G. parasuis, and offered a fresh perspective on therapeutic strategies.

Although effort-reward imbalance has been proven to affect academic burnout, how effort-reward imbalance affects academic burnout remains unclear. This study, from the perspective of learning satisfaction and resilience, investigates how effort-reward imbalance affects academic burnout and reveals the influence of effort-reward imbalance on academic burnout. A sample of 755 junior high school students was assessed using the Revised Effort-Reward Imbalance for Learning Scale, Revised Learning Satisfaction Scale, Academic Burnout Scale, and Resilience Scale. Junior high school students’ effort-reward imbalance rates for learning, learning satisfaction, and academic burnout were all significantly correlated with each other; learning satisfaction mediated the relationship between them. Learning satisfaction mediated the relationship between junior high school students’ effort-reward imbalance rate for learning and academic burnout, and resilience negatively moderated the path from junior high school students’ effort-reward imbalance rate from learning to learning satisfaction. The results suggest that improving students’ resilience can effectively decrease the negative effects of effort-reward imbalance.

Purpose: To determine the effect of triptolide on rheumatoid arthritis, and the underlying mechanism of action. Methods: Sixty Sprague Dawley (SD) rats were assigned to blank control, model, methotrexate, and triptolide groups (n = 15/group). A rat model of rheumatoid arthritis was established. Each group was given the corresponding treatment. Toe edema and arthritis index of rats were assessed in all the groups. Levels of IL-2, IFN-γ, TNF-α, IL-6, IL-8, and IL-10 were evaluated by enzyme-linked immunosorbent assay (ELISA). Results: Serum levels of IL-2, IFN-γ, TNF-α, IL-6 and IL-8 were significantly higher in model rats than in blank control, while IL-10 level was significantly lower (p < 0.05). In triptolide group, serum IL-2, IFN-γ, TNF-α, IL-6 and IL-8 were significantly lower than the corresponding levels in model group, but IL-10 was significantly higher. The relative mRNA and protein concentrations of Notch1 and Jagged1 were significantly higher in model rats than in blank control rats, but significantly lower, relative to model rats. Conclusion: Tripterygium wilfordii exerts a good therapeutic effect in the treatment of rheumatoid arthritis in rats, most likely by inhibiting the activation of Notch1/Jagged1 signal pathway. Thus, it regulates inflammation by regulating the expressions of various inflammatory cytokines, and may be potential agent for the management of rheumatoid arthritis. [ABSTRACT FROM AUTHOR]