Precise modification of the surface charge of antigen enhances vaccine immunogenicity.

Aluminum (alum) adjuvant is the most extensively used protein subunit vaccine adjuvant, and its effectiveness and safety have been widely recognized. The surface charge of the antigen determines its electrostatic adsorption to alum adjuvant, which directly affects the immune efficacy of the protein vaccine. In our study, we precisely modified its surface charge by inserting charged amino acids into the flexible region of the SARS-CoV-2 receptor-binding domain (RBD), achieving electrostatic adsorption and a site-specific anchor between the immunogen and alum adjuvant. This innovative strategy extended the bioavailability of the RBD and directionally displayed the neutralizing epitopes, thereby significantly enhancing humoral and cellular immunity. Furthermore, the required dose of antigen and alum adjuvant was greatly reduced, which improved the safety and accessibility of the protein subunit vaccine. On this basis, the wide applicability of this novel strategy to a series of representative pathogen antigens such as SARS-RBD, MERS-RBD, Mpox-M1, MenB-fHbp, and Tularemia-Tul4 was further confirmed. Charge modification of antigens provides a straightforward approach for antigenicity optimization of alum-adjuvanted vaccines, which has great potential to be adopted as a global defense against infectious diseases.

Impacts of social distancing measures on global supply chain configuration

World Health Organisation has advised governments to prevent the spread of COVID-19 by introducing stringent social distancing measures (SDMs) in five levels, ranging from pandemic surveillance, stay-at-home recommendations, workplace closures, to national and international travel restrictions. These measures inevitably disrupt global business environment and supply chain configuration. Existing literature does not comprehensively analyze the five-level SDMs' impacts on firms and supply chains. Thus, we established a mixed-integer programming model to integrate environment changes in lead time and cost for transportation and processing, market size, and the number of countries (NoC) imposing the SDMs. Sensitivity analysis is conducted to evaluate propagation impacts on global supply chains when the SDMs are imposed on firms in different echelons of supply chains. Results show that (i) supply chain losses and disruptions primarily depend on the NoC, followed by restricted transportation, market size, and processing limitations. (ii) When the SDMs, especially restrictions on transportation, are implemented in downstream echelons, the propagation impacts on supply chains and firms become more significant. (iii) Compared with elastic-demand supply chains, the fixed-demand one, e.g. food supply chain, suffers more significantly with the stringent SDMs and high holding costs. Finally, managerial implications are discussed from supply chains, firms, and policymakers.

Impacts of delta and omicron variants on inactivated SARS-CoV-2 vaccine-induced T cell responses in patients with autoimmune diseases and healthy controls.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (COVID-19), which is still devastating economies and communities globally. The increasing infections of variants of concern (VOCs) in vaccinated population have raised concerns about the effectiveness of current vaccines. Patients with autoimmune diseases (PAD) under immunosuppressant treatments are facing higher risk of infection and potentially lower immune responses to SARS-CoV-2 vaccination. METHODS: Blood samples were collected from PAD or healthy controls (HC) who finished two or three doses of inactivated vaccines. Spike peptides derived from wild-type strain, delta, omicron BA.1 were utilised to evaluate T cell responses and their cross-recognition of delta and omicron in HC and PAD by flow cytometry and ex vivo IFNγ-ELISpot. RESULTS: We found that inactivated vaccine-induced spike-specific memory T cells were long-lasting in both PAD and HC. These spike-specific T cells were highly conserved and cross-recognized delta and omicron. Moreover, a third inactivated vaccine expanded spike-specific T cells that responded to delta and omicron spike peptides substantially in both PAD and HC. Importantly, the polyfunctionality of spike-specific memory T cells was preserved in terms of cytokine and cytotoxic responses. Although the extent of T cell responses was lower in PAD after two-dose, T cell responses were boosted to a greater magnitude in PAD by the third dose, bringing comparable spike-specific T cell immunity after the third dose. CONCLUSION: Inactivated vaccine-induced spike-specific T cells remain largely intact against delta and omicron variants. This study expands our understanding of inactivated vaccine-induced T cell responses in PAD and HC, which could have important indications for vaccination strategy.

Significant alterations of intestinal symbiotic microbiota induced by intraperitoneal vaccination mediate changes in intestinal metabolism of NEW Genetically Improved Farmed Tilapia (NEW GIFT, Oreochromis niloticus).

BACKGROUND: After millions of years of coevolution, symbiotic microbiota has become an integral part of the host and plays an important role in host immunity, metabolism, and health. Vaccination, as an effective means of preventing infectious diseases, has been playing a vital role in the prevention and control of human and animal diseases for decades. However, so far, minimal is known about the effect of vaccination on fish symbiotic microbiota, especially mucosal microbiota, and its correlation with intestinal metabolism remains unclear. METHODS: Here we reported the effect of an inactivated bivalent Aeromonas hydrophila/Aeromonas veronii vaccine on the symbiotic microbiota and its correlation with the intestinal metabolism of farmed adult Nile tilapia (Oreochromis niloticus) by 16S rRNA gene high-throughput sequencing and gas chromatography-mass spectrometry metabolomics. RESULTS: Results showed that vaccination significantly changed the structure, composition, and predictive function of intestinal mucosal microbiota but did not significantly affect the symbiotic microbiota of other sites including gill mucosae, stomach contents, and stomach mucosae. Moreover, vaccination significantly reduced the relative abundance values of potential opportunistic pathogens such as Aeromonas, Escherichia-Shigella, and Acinetobacter in intestinal mucosae. Combined with the enhancement of immune function after vaccination, inactivated bivalent Aeromonas vaccination had a protective effect against the intestinal pathogen infection of tilapia. In addition, the metabolite differential analysis showed that vaccination significantly increased the concentrations of carbohydrate-related metabolites such as lactic acid, succinic acid, and gluconic acid but significantly decreased the concentrations of multiple lipid-related metabolites in tilapia intestines. Vaccination affected the intestinal metabolism of tilapia, which was further verified by the predictive function of intestinal microbiota. Furthermore, the correlation analyses showed that most of the intestinal differential microorganisms were significantly correlated with intestinal differential metabolites after vaccination, confirming that the effect of vaccination on intestinal metabolism was closely related to the intestinal microbiota. CONCLUSIONS: In conclusion, this paper revealed the microbial and metabolic responses induced by inactivated vaccination, suggesting that intestinal microbiota might mediate the effect of vaccination on the intestinal metabolism of tilapia. It expanded the novel understanding of vaccine protective mechanisms from microbial and metabolic perspectives, providing important implications for the potential influence of vaccination on human intestinal microbiota and metabolism. Video Abstract.

Associations between coping styles, gender, their interaction and non-suicidal self-injury among middle school students in rural west China: A multicentre cross-sectional study.

Background: To investigate the association between coping styles, gender, their interactions and non-suicidal self-injurious (NSSI) behaviors among middle school students in rural western China under COVID-19. Methods: A multicentre cross-sectional study method was used to conduct an online survey of 8,361 students from 23 middle schools in the northern Sichuan region by clustering sampling, using the General Information Questionnaire, the Ottawa Self-Injury Inventory, and the Coping Style Scale for Middle School Students. Results: The past year prevalence of NSSI among middle school students in rural west China was 5.7%. The differences in scores between those with and without NSSI on all dimensions of coping styles were statistically significant (p < 0.001). Multivariate logistic regression analysis revealed that vocational high school (OR = 1.67), girls (OR = 2.5), single parent with divorced parents (OR = 1.89), remarriage with divorced parents (OR = 1.81), and tolerance (OR = 1.17), venting emotions (OR = 1.15) and fantasy/denial (OR = 1.07) in coping styles may increase the risk of NSSI among middle school students, while problem solving (OR = 0.9) and seeking social support (OR = 0.9) among coping styles may reduce the risk of NSSI among middle school students. The interaction results show that gender has a moderating role in the process of endurance, avoidance, venting of emotions, and fantasy/denial influencing non-suicidal self-injury in middle school students. Conclusion: There is an association between coping styles and self-injury among middle school students in rural areas in western China, with gender playing a moderating role. Active attention should be paid to students' coping styles and encouraging them to adopt positive coping styles as well as avoid negative coping styles, especially in the case of girls, which can help prevent self-injury.

Clinical cardiovascular emergencies and the cellular basis of COVID-19 vaccination: from dream to reality?

OBJECTIVES: SARS-CoV-2 is responsible for the global COVID-19 pandemic, with little prevention or treatment options. More than 600 million mortalities have been documented from SARS-CoV-2 infection, with the majority of fatalities occurring among elderly patients (aged >65 years). A number of vaccines have been developed in an effort to restrain the rapid spread of SARS-CoV-2. Considering the widespread administration of these vaccines, substantial side or undesired effects in multiple organ systems have emerged, necessitating essential critical care. Herein, we tabulate the adverse cardiovascular responses resulting from COVID-19 vaccines. DESIGN OR METHODS: We searched PubMed for articles published through April, 2022, with the terms "SARS-CoV-2", "COVID-19", "cardiovascular", "SARS-CoV-2 vaccines", "COVID-19 vaccines", "myocarditis", "pericarditis", "thrombosis", "thrombocytopenia", "vaccine-induced thrombotic thrombocytopenia", "acute coronary syndrome", "myocardial infarction", "hypertension", "arrythmia", "postural orthostatic tachycardia syndrome", "Takotsubo cardiomyopathy", "cardiac arrest" and "death". We mainly selected publications from the past 3 years, but did not exclude widely referenced and highly regarded older publications. Besides, we searched the reference lists of articles identified by above search method and chose those we considered relevant. RESULTS: COVID-19 vaccines evoke rare but fatal thrombotic events, whereas messenger RNA\055based vaccines appear to be associated with risks of pericarditis/myocarditis, with the latter being more predominant in young adults following the second dose. Reports of other cardiovascular responses, including hypertension, arrhythmia, acute coronary syndrome, and cardiac arrest, have also been indicated. CONCLUSION: The undesired cardiovascular complications remain infrequent, giveng the large number of vaccinations inoculated to general population. And lower mortality takes precedence over the undesired cardiovascular complications.

Associations between coping styles, gender, their interaction and non-suicidal self-injury among middle school students in rural west China: A multicentre cross-sectional study

Background To investigate the association between coping styles, gender, their interactions and non-suicidal self-injurious (NSSI) behaviors among middle school students in rural western China under COVID-19. Methods A multicentre cross-sectional study method was used to conduct an online survey of 8,361 students from 23 middle schools in the northern Sichuan region by clustering sampling, using the General Information Questionnaire, the Ottawa Self-Injury Inventory, and the Coping Style Scale for Middle School Students. Results The past year prevalence of NSSI among middle school students in rural west China was 5.7%. The differences in scores between those with and without NSSI on all dimensions of coping styles were statistically significant (p < 0.001). Multivariate logistic regression analysis revealed that vocational high school (OR = 1.67), girls (OR = 2.5), single parent with divorced parents (OR = 1.89), remarriage with divorced parents (OR = 1.81), and tolerance (OR = 1.17), venting emotions (OR = 1.15) and fantasy/denial (OR = 1.07) in coping styles may increase the risk of NSSI among middle school students, while problem solving (OR = 0.9) and seeking social support (OR = 0.9) among coping styles may reduce the risk of NSSI among middle school students. The interaction results show that gender has a moderating role in the process of endurance, avoidance, venting of emotions, and fantasy/denial influencing non-suicidal self-injury in middle school students. Conclusion There is an association between coping styles and self-injury among middle school students in rural areas in western China, with gender playing a moderating role. Active attention should be paid to students' coping styles and encouraging them to adopt positive coping styles as well as avoid negative coping styles, especially in the case of girls, which can help prevent self-injury.

Force application of laparoscopic surgeons under the impact of heavy personal protective equipment during COVID-19 pandemic.

Objective: Surgeons are required to wear heavy personal protective equipment while delivering care to patients during the COVID-19 pandemic. We examined the impact of wearing double gloves on surgeons' performance in laparoscopic surgery. Methods: Eleven surgeons-in-training at the Surgical Simulation Research Lab of the University of Alberta were recruited to perform laparoscopic cutting tasks in simulation while wearing none, one pair, and two pairs of surgical gloves. Forces applied to laparoscopic instruments were measured. Results: Wearing gloves prolonged task times (one pair of gloves: 301.6 ± 61.7 s; two pairs of gloves: 295.8 ± 65.3 s) compared with no gloves (241.7 ± 46.9 s; p = 0.043). Wearing double gloves increased cutting errors (20.4 ± 5.1 mm2) compared with wearing one pair of gloves (16.9 ± 5.5 mm2) and no gloves (14.4 ± 4.6 mm2; p = 0.030). Wearing gloves reduced the peak force (one pair of gloves: 2.4 ± 0.7 N; two pairs of gloves: 2.7 ± 0.6 N; no gloves: 3.4 ± 1.4 N; p = 0.049), and the total force (one pair of gloves: 10.1 ± 2.8 N; two pairs of gloves: 10.3 ± 2.6 N; no glove: 12.6 ± 1.9 N; p = 0.048) delivered onto laparoscopic scissors compared with wearing no glove. Conclusion: The combined effects of wearing heavy gloves and using tools reduced the touching sensation, which limited the surgeons' confidence in performing surgical tasks. Increasing practice in simulation is suggested to allow surgeons to overcome difficulties brought by personal protective equipment.

Etiological characteristics of "tail blister disease" of Australian redclaw crayfish (Cherax quadricarinatus).

In November 2019, an acute disease outbreak in Australian redclaw crayfish (Cherax quadricarinatus) occurred in a farm in Hubei, China, with a cumulative mortality rate of over 80%. One of the characteristic symptoms of the disease was blisters on the tail. This symptom is also common in diseased Procambarus clarkii every year in this country, but the causative agent has not been determined. This study analyzed the etiological characteristics of this disease. Bacterial isolation and identification combined with high-throughput sequencing analysis were conducted to obtain the microbiota characteristics in the hemolymph, hepatopancreas, and intestines. Results showed that this outbreak was caused by infection from Aeromonas hydrophila and Aeromonas veronii. The underlying cause was stress imposed on crayfish during transferring from outdoor pond to indoor pond because of temperature drops. Aeromonas infection caused remarkable changes in the structure of the microbial composition in the hemolymph, hepatopancreas, and intestines of the crayfish. The abundance of Aeromonas in the hemolymph of the sick crayfish was as high as 99.33%. In particular, KEGG metabolic pathway analysis showed that some antibiotic synthesis, enterobactin biosynthesis, and myo-inositol degradation pathways were abundant in healthy crayfish hemolymphs, which may be the mechanism of maintaining crayfish health. Conversely, inhibition of these pathways led to the disorder of microbiota structure, finally leading to the occurrence of diseases. To the knowledge of the authors, this study was the first to use high-throughput amplicon sequencing targeting the 16S rRNA gene to find the causative bacteria in aquatic animals. This protocol can provide more comprehensive and reliable evidence for pathogen identification, even if the pathogenic bacteria are anaerobes or other hard-to-culture bacteria.

Obesity cardiomyopathy: evidence, mechanisms, and therapeutic implications.

The prevalence of heart failure is on the rise and imposes a major health threat, in part, due to the rapidly increased prevalence of overweight and obesity. To this point, epidemiological, clinical, and experimental evidence supports the existence of a unique disease entity termed "obesity cardiomyopathy," which develops independent of hypertension, coronary heart disease, and other heart diseases. Our contemporary review evaluates the evidence for this pathological condition, examines putative responsible mechanisms, and discusses therapeutic options for this disorder. Clinical findings have consolidated the presence of left ventricular dysfunction in obesity. Experimental investigations have uncovered pathophysiological changes in myocardial structure and function in genetically predisposed and diet-induced obesity. Indeed, contemporary evidence consolidates a wide array of cellular and molecular mechanisms underlying the etiology of obesity cardiomyopathy including adipose tissue dysfunction, systemic inflammation, metabolic disturbances (insulin resistance, abnormal glucose transport, spillover of free fatty acids, lipotoxicity, and amino acid derangement), altered intracellular especially mitochondrial Ca2+ homeostasis, oxidative stress, autophagy/mitophagy defect, myocardial fibrosis, dampened coronary flow reserve, coronary microvascular disease (microangiopathy), and endothelial impairment. Given the important role of obesity in the increased risk of heart failure, especially that with preserved systolic function and the recent rises in COVID-19-associated cardiovascular mortality, this review should provide compelling evidence for the presence of obesity cardiomyopathy, independent of various comorbid conditions, underlying mechanisms, and offer new insights into potential therapeutic approaches (pharmacological and lifestyle modification) for the clinical management of obesity cardiomyopathy.