The role of digestive system diseases in cerebrovascular disease: a comprehensive Mendelian randomization study.

Background: Cerebrovascular disease, among the most prevalent neurological disorders, poses a substantial threat to human health with its elevated mortality and disability rates, placing considerable strain on healthcare systems. Although several studies in recent years have suggested a potential association between digestive system diseases and cerebrovascular diseases, the findings remain inconsistent. Methods: Genome-wide association study (GWAS) summary data for 12 digestive diseases and cerebrovascular diseases were used to conduct Mendelian randomization (MR) analysis. In this investigation, we endeavored to elucidate the causal relationship between digestive system diseases and cerebrovascular diseases. Employing a comprehensive approach, including two-sample MR (TSMR), multivariate MR (MVMR), and two-step MR analysis, we leveraged summary statistics data obtained from published GWAS. The primary analysis method employed was inverse variance weighted (IVW), with MR-Egger and weighted median (WM) as secondary methods. Sensitivity analysis included heterogeneity testing, horizontal multivariate testing, MR-PRESSO, and a "leave-one-out" method. Additionally, the F-statistic was utilized to assess the strength of instrumental variables, ensuring robust results. Results: In the TSMR analysis, this study found a significant causal relationship between genetically predicted gastroesophageal reflux disease (GERD) and any stroke (AS), any ischemic stroke (AIS), large-artery atherosclerotic stroke (LAS), intracranial aneurysm (IA), and subarachnoid hemorrhage (SAH). In MVMR analysis, this study found that even after adjusting for systolic blood pressure (SBP), body mass index (BMI) and type 2 diabetes (T2D), the causal relationship remains exist. In the two-step MR mediation analysis, it was found that BMI, SBP and T2D play mediating role in the causal relationship between GERD and cerebrovascular diseases. Conclusion: This study indicates a clear positive causal relationship between GERD and cerebrovascular diseases, and this causal association remains significant even after adjusting for BMI, SBP and T2D. The mediation MR analysis suggests that BMI, SBP and T2D may mediate the causal relationship between GERD and the risk of cerebrovascular diseases.

Effects of straw management and N levels on gross nitrogen transformations in fluvo-aquic soil of the North China Plain.

Straw incorporation with nitrogen (N) fertilization is crucial for enhancing soil fertility and minimizing negative environmental impacts by altering the magnitude and direction of soil N transformation processes. However, the response of soil N transformations to long-term carbon (C) and N inputs, and their primary driving factors, remain poorly understood. Thus, a 15N tracing study was conducted to investigate the effects of straw incorporation (AS) and straw removal (NS) with N levels of 0, 150 and 250 kg N ha-1 per season (N0, N150 and N250) on gross N transformation rates in the North China Plain after 6-year trial. Results indicated that at N0, AS significantly increased soil microbial immobilization of nitrate (NO3--N, INO3) and autotrophic nitrification rates (ONH4) compared to NS. With N fertilization, AS increased gross N immobilization (Itotal), ammonium-N immobilization (NH4+-N, INH4), net NH4+-N immobilization (InetNH4) and net NH4+-N absorption rates (AnetNH4). Specifically, at N150, AS significantly increased recalcitrant organic N mineralization rate (MNrec), while significantly reducing ONH4, labile organic N mineralization (MNlab), and gross N mineralization rates (Mtotal). At N250, AnetNH4, MNlab, MNrec and ONH4 under AS were significantly higher than under NS. Nitrogen application significantly increased ONH4, Itotal and INO3 under two straw management practices, and enhanced INH4 and InetNH4 under AS. Compared to N250, N150 significantly increased INH4 and InetNH4 under AS, while decreasing Mtotal. Opposite results were observed under NS. Meanwhile, NO3--N and dissolved organic carbon (DOC) were master factors controlling immobilization, total nitrogen (TN), hydrolysable NH4+-N (HNN) and stable organic N significantly affected AnetNH4, while labile organic N were the key environmental factors affecting MNrec, all of which positively influenced the rates of assimilation, mineralization and clay mineral adsorption. Overall, this study provides new insights into reducing N fertilization under straw incorporation by quantifying soil N transformation processes.

Association Between ACE2 and Lung Diseases.

Angiotensin-converting enzyme 2 (ACE2) is an important regulator of the Renin-Angiotensin System (RAS). Additionally, it has been identified as a functional receptor for the Coronavirus. Research indicates that ACE2 plays a role in the regulation of cardiovascular systems by modulating blood pressure and electrolyte balance. Its role in pulmonary diseases has also garnered significant attention due to the widespread prevalence of Coronavirus. There is solid evidence linking ACE2 to other pulmonary diseases, including chronic obstructive pulmonary disease, acute respiratory distress syndrome, allergic asthma, among others. However, the exact pathological and physiological mechanisms of ACE2 in these diseases remain elusive. Our research aims to review and explore the latest advancements in ACE2-related studies in pulmonary diseases. These findings have the potential to open new avenues for utilizing ACE2 as a potential biomarker for early diagnosis and monitoring of pulmonary diseases.

Associations of serum vitamin B12 and its biomarkers with musculoskeletal health in middle-aged and older adults.

Introduction: The effects of vitamin B12 metabolism on musculoskeletal health and the exact mechanism have not been fully determined. Our study aimed to assess the association of vitamin B12 and its biomarkers with musculoskeletal health in middle-aged and older adults. Methods: The data from the National Health and Nutrition Examination Survey 2001-2002 were used to investigate the effects of serum vitamin B12 and its biomarkers (homocysteine and methylmalonic acid) on skeletal muscle health. Bone mineral density (BMD), lean mass, gait speed and knee extensor strength were used as indicators for musculoskeletal health. Results: Serum vitamin B12 level was positively correlated with the total and appendicular lean mass (ß = 584.83, P = 0.044; ß = 291.65, P = 0.043) in older adults over 65 years of age. In the full population, plasma homocysteine was associated with total lean mass, appendicular lean mass, gait speed, and knee extensor strength (all P < 0.05). Among older adults over 65 years of age, homocysteine level was significantly negatively correlated with gait speed and knee extensor strength (ß = -12.75, P = 0.019; ß = -0.06, P <0.001). Plasma methylmalonic acid was negatively associated with total BMD and femur BMD in the full population (ß = -0.01, P = 0.018; ß = -0.01, P = 0.004). In older adults, methylmalonic acid significantly affected total BMD, femur BMD and knee extensor strength (ß = -0.01, P = 0.048; ß = -0.01, P = 0.025; ß = -7.53, P = 0.015). Conclusions: Vitamin B12 and its biomarkers are closely related to BMD, body composition, muscle strength and physical function in middle-aged and older adults. Vitamin B12 may be an important indicator of musculoskeletal health in the elderly.

African swine fever virus pB318L, a trans-geranylgeranyl-diphosphate synthase, negatively regulates cGAS-STING and IFNAR-JAK-STAT signaling pathways.

African swine fever (ASF) is an acute, hemorrhagic, and severe infectious disease caused by the ASF virus (ASFV). ASFV has evolved multiple strategies to escape host antiviral immune responses. Here, we reported that ASFV pB318L, a trans-geranylgeranyl-diphosphate synthase, reduced the expression of type I interferon (IFN-I) and IFN-stimulated genes (ISGs). Mechanically, pB318L not only interacted with STING to reduce the translocation of STING from the endoplasmic reticulum to the Golgi apparatus but also interacted with IFN receptors to reduce the interaction of IFNAR1/TYK2 and IFNAR2/JAK1. Of note, ASFV with interruption of B318L gene (ASFV-intB318L) infected PAMs produces more IFN-I and ISGs than that in PAMs infected with its parental ASFV HLJ/18 at the late stage of infection. Consistently, the pathogenicity of ASFV-intB318L is attenuated in piglets compared with its parental virus. Taken together, our data reveal that B318L gene may partially affect ASFV pathogenicity by reducing the production of IFN-I and ISGs. This study provides a clue to design antiviral agents or live attenuated vaccines to prevent and control ASF.

Optical assembly of multi-particle arrays by opto-hydrodynamic binding of microparticles close to a one-dimensional chain of magnetic microparticles.

Two-dimensional materials possess a large number of interesting and important properties. Various methods have been developed to assemble two-dimensional aggregates. Assembly of colloidal particles can be achieved with laser-heating-induced thermal convective flow. In this paper, an opto-hydrodynamic binding method is proposed to assemble colloidal particles dispersed in a solution into multilayer structures. First, we use polystyrene (PS) microspheres to study the feasibility and characteristics of the assembly method. PS microspheres and monodispersed magnetic silica microspheres (SLEs) are dispersed in a solution to form a binary mixture system. Under the action of an external uniform magnetic field, SLEs in the solution form chains. An SLE chain is heated by a laser beam. Due to the photothermal effect, the SLE chain is heated to produce a thermal gradient, resulting in thermal convection. The thermal convection drives the PS beads to move toward the heated SLE chain and finally stably assemble into multilayer aggregates on both sides of the SLE chain. The laser power affects the speed and result of the assembly. When the laser power is constant, the degree of constraint of the PS microbeads in different layers is also different. At the same time, this method can also assemble the biological cells, and the spacing of different layers of cells can be changed by changing the electrolyte concentration of the solution. Our work provides an approach to assembling colloidal particles and cells, which has a potential application in the analysis of the collective dynamics of microparticles and microbes.

An annotated street view image dataset for automated road damage detection.

Road damage is a great threat to the service life and safety of roads, and the early detection of pavement damage can facilitate maintenance and repair. Street view images serve as a new solution for the monitoring of pavement damage due to their wide coverage and regular updates. In this study, a road pavement damage dataset, the Street View Image Dataset for Automated Road Damage Detection (SVRDD), was developed using 8000 street view images acquired from Baidu Maps. Based on these images, over 20,000 damage instances were visually recognized and annotated. These instances were distributed in five administrative districts of Beijing City. Ten well-established object detection algorithms were trained and assessed using the SVRDD dataset. The results have demonstrated the performances of these algorithms in the detection of pavement damages. To the best of our knowledge, SVRDD is the first public dataset based on street view images for pavement damages detection. It can provide reliable data support for future development of deep learning algorithms based on street view images.

The attenuated African swine fever vaccine HLJ/18-7GD provides protection against emerging prevalent genotype II variants in China.

Genetic changes have occurred in the genomes of prevalent African swine fever viruses (ASFVs) in the field in China, which may change their antigenic properties and result in immune escape. There is usually poor cross-protection between heterogonous isolates, and, therefore, it is important to test the cross-protection of the live attenuated ASFV vaccines against current prevalent heterogonous isolates. In this study, we evaluated the protective efficacy of the ASFV vaccine candidate HLJ/18-7GD against emerging isolates. HLJ/18-7GD provided protection against a highly virulent variant and a lower lethal isolate, both derived from genotype II Georgia07-like ASFV and isolated in 2020. HLJ/18-7GD vaccination prevented pigs from developing ASF-specific clinical signs and death, decreased viral shedding via the oral and rectal routes, and suppressed viral replication after challenges. However, HLJ/18-7GD vaccination did not provide solid cross-protection against genotype I NH/P68-like ASFV challenge in pigs. HLJ/18-7GD vaccination thus shows great promise as an alternative strategy for preventing and controlling genotype II ASFVs, but vaccines providing cross-protection against different ASFV genotypes may be needed in China.

Warm Temperature Increments Strengthen the Crosstalk between Roots and Soil in the Rhizosphere of Soybean Seedlings.

The plant rhizosphere underlies the crosstalk between plant and soil and has a crucial role in plant growth and development under various environments. We examined the effect of temperature rise on the rhizosphere environment of soybean roots to clarify the rhizosphere crosstalk between roots and soil in response to warm temperature rises in a global warming background. The in situ results of root enzyme activity revealed that soybean roots secrete ß-glucosidase, and enzyme spectrum imaging demonstrated different enzymatic activities under different temperature environments. The soil enzyme kinetics results showed that soil enzymatic activity increased with increasing temperature, and soybean rhizosphere soil enzymatic activity was higher than that of non-rhizosphere soil. Rhizosphere soil and non-rhizosphere soil showed that the dominant bacterial phylum in soybean rhizosphere soil was Acidobacteria, and the dominant bacterial genus was JG30-KF-AS9. Compared with non-rhizosphere soil, rhizosphere soil was more nutrient-rich, and root secretions provided abundant carbon sources and other nutrients for soil microorganisms in the rhizosphere. Rhizosphere microorganisms affect plant growth by influencing the decomposition of soil organic carbon. The organic carbon content of rhizosphere soil was higher than that of non-rhizosphere soil under high temperatures.

Expression and Prognostic Value of m6A RNA Methylation-Related Genes in Thyroid Cancer.

Background: N6-methyladenosine (m6A) methylation modification is involved in tumorigenesis and progression and can affect various stages of RNA processing. We aimed to determine m6A methylation modifications on a transcriptome-wide scale in thyroid cancer. Methods: RNA samples from cancerous tissues and adjacent tissues extracted from patients with papillary thyroid carcinoma (PTC) from Hangzhou First People's Hospital, Zhejiang, China from January 2019 to January 2020 were used for m6A-sequencing. The biological function of differentially expressed genes (DEGs) was analyzed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Correlation analysis between the results of transcriptome sequencing and m6A-sequencing was also performed. The key m6A immune-related genes were downloaded from Immport. LASSO regression was performed on the resulting genes to establish a prognostic risk model, which was verified by multivariate Cox proportional hazards regression analyses, receiver operating characteristic (ROC) curves and Kaplan-Meier survival analysis. Results: An increase in m6A content in the total RNA of PTC was observed. A total of 123 genes with significant differential expression and differential methylation sites in thyroid cancer were selected, related to protein digestion and absorption, linoleic acid metabolism, legionellosis and alpha-linolenic acid metabolism. Seven genes (GDNF, EBI3, CCL2, BMP5, TGFB2, CGB3 and RLN2) were found to be predictive of PTC. Conclusion: We analyzed the expression, enrichment pathways and functions of m6A methylation-related genes in the whole transcriptome of thyroid cancer and provided a prognostic risk model for thyroid cancer patients.

A Multi-perspective Model for Protein-Ligand-Binding Affinity Prediction.

Gathering information from multi-perspective graphs is an essential issue for many applications especially for protein-ligand-binding affinity prediction. Most of traditional approaches obtained such information individually with low interpretability. In this paper, we harness the rich information from multi-perspective graphs with a general model, which abstractly represents protein-ligand complexes with better interpretability while achieving excellent predictive performance. In addition, we specially analyze the protein-ligand-binding affinity problem, taking into account the heterogeneity of proteins and ligands. Experimental evaluations demonstrate the effectiveness of our data representation strategy on public datasets by fusing information from different perspectives. All codes are available in the https://github.com/Jthy-af/HaPPy .

Survival improvements of marine mammals in zoological institutions mirror historical advances in human longevity.

An intense public debate has fuelled governmental bans on marine mammals held in zoological institutions. The debate rests on the assumption that survival in zoological institutions has been and remains lower than in the wild, albeit the scientific evidence in support of this notion is equivocal. Here, we used statistical methods previously applied to assess historical improvements in human lifespan and data on 8864 individuals of four marine mammal species (harbour seal, Phoca vitulina; California sea lion, Zalophus californianus; polar bear, Ursus maritimus; common bottlenose dolphin, Tursiops truncatus) held in zoos from 1829 to 2020. We found that life expectancy increased up to 3.40 times, and first-year mortality declined up to 31%, during the last century in zoos. Moreover, the life expectancy of animals in zoos is currently 1.65-3.55 times longer than their wild counterparts. Like humans, these improvements have occurred concurrently with advances in management practices, crucial for population welfare. Science-based decisions will help effective legislative changes and ensure better implementation of animal care.

Fahr's disease linked to a novel mutation in MYORG variants manifesting as paroxysmal limb stiffness and dysarthria: Case report and literature review.

BACKGROUND: Primary familial brain calcification (PFBC) is a rare hereditary neurodegenerative disorder associated with the MYORG gene; however, the clinical and radiological characteristics of MYORG-PFBC remain unclear. METHODS: We present relevant medical data obtained from a patient affected by PFBC with a novel MYORG variant and conducted a mutational analysis of MYORG in her family members. We reviewed all reported PFBC cases with biallelic MYORG mutations until April 1, 2023, and summarized the associated clinical and radiological features and mutation sites. RESULTS: The patient (22-year-old woman) exhibited paroxysmal limb stiffness and dysarthria for 3 years. Computed tomography revealed calcifications in the paraventricular white matter, basal ganglia, thalamus, and cerebellum. Whole-exome sequencing revealed a novel homozygous frameshift variant (c.743delG: p.G248Afs*32) in exon 2 of the MYORG gene (NM_020702.5). To date, 62 families and 64 mutation sites have been reported. Among the reported biallelic MYORG mutations, 57% were homozygous and 43% were compound heterozygous. Individuals with biallelic MYORG mutations experience more severe brain calcification with approximately 100% clinical penetrance. Ten single heterozygous mutation sites are associated with significant brain calcifications. CONCLUSION: All patients with primary brain calcification, particularly younger patients without a family history of the disease, should be screened for MYORG mutations.

Development of a new effective African swine fever virus vaccine candidate by deletion of the H240R and MGF505-7R genes results in protective immunity against the Eurasia strain.

IMPORTANCE: African swine fever (ASF) caused by ASF virus (ASFV) is a highly contagious and acute hemorrhagic viral disease in domestic pigs. Until now, no effective commercial vaccine and antiviral drugs are available for ASF control. Here, we generated a new live-attenuated vaccine candidate (ASFV-ΔH240R-Δ7R) by deleting H240R and MGF505-7R genes from the highly pathogenic ASFV HLJ/18 genome. Piglets immunized with ASFV-ΔH240R-Δ7R were safe without any ASF-related signs and produced specific antibodies against p30. Challenged with a virulent ASFV HLJ/18, the piglets immunized with high-dose group (105 HAD50) exhibited 100% protection without clinical symptoms, showing that low levels of virus replication with no observed pathogenicity by postmortem and histological analysis. Overall, our results provided a new strategy by designing live-attenuated vaccine candidate, resulting in protection against ASFV infection.

Gut microbiota and cerebrovascular diseases: a Mendelian randomization study.

Background: The causal relationship between gut microbiota and cerebrovascular disease remains unknown, despite several recent studies reporting an association between the two. Methods: To assess this relationship, we conducted a two-sample Mendelian randomization (MR) using summary statistics data from published genome-wide association studies (GWAS). This analysis allowed us to identify bacterial taxa that may affect cerebrovascular disease. Furthermore, we performed reverse MR to further analyze the significant bacterial taxa. Finally, we conducted a two-step MR analysis to examine the mediating role of metabolic factors [systolic blood pressure (SBP), type 2 diabetes (T2D), and body mass index (BMI)] in the association between gut microbiota and cerebrovascular disease. Additionally, a series of sensitivity analyses were carried out to validate the robustness of our findings. Results: Our results showed that a genetically predicted high abundance of family Porphyromonadaceae reduced the risk of intracranial aneurysms (IA). Moreover, using inverse variance weighted (IVW) estimates, we found a nominal causal relationship between seventeen gut microbiota and IA, as well as its subtypes. In the case of stroke and its subtypes, we observed a nominal causal relationship with thirteen, eleven, eleven, nine, and eight bacteria for AS, AIS, CES, LAS, and SVS, respectively. Reverse MR analysis showed no significant causal relationship between intracranial aneurysms and gut microbiota. However, we did find that genetically predicted any stroke (AS) and any ischemic stroke (AIS) reduced the abundance of family Clostridiaceae1 (OR: 0.74, 95% CI: 0.62-0.87, p = 3.39 × 10-4, and OR: 0.75, 95% CI: 0.66-0.87, p = 7.06 × 10-5, respectively). Furthermore, genetic prediction of AIS (OR: 0.87, 95% CI: 0.77-0.99, p = 3.05 × 10-2) was associated with a reduced abundance of the order Clostridiales. Moreover, genus Streptococcus exhibited effects on AS, AIS, and SVS which were mediated by T2D. Conversely, the association between genus Eubacterium brachy group and AIS was mediated by SBP. No significant heterogeneity of instrumental variables or horizontal pleiotropy was observed. Conclusion: This MR analysis indicates that there exists a beneficial or detrimental causal effect of gut microbiota composition on cerebrovascular disease. And SBP and T2D may play mediating role in this process.

Associations of lipids and lipid-lowering drugs with risk of stroke: a Mendelian randomization study.

Background: Stroke is a leading cause of death worldwide, but it is unclear whether circulating lipids and lipid-lowering drugs are causally associated with stroke and its subtypes. Methods: We used two-sample Mendelian randomization (MR) to examine the effects of blood lipids and lipid-lowering drugs on stroke and its subtypes. Results: The inverse variance weighted Mendelian randomization (IVW-MR) revealed the low-density lipoprotein cholesterol (LDL-C) (OR, 1.46; 95% CI, 1.17-1.83; p = 0.0008) and apolipoprotein B (apoB) (OR, 1.46; 95% CI, 1.21-1.77; p = 0.0001) was positively correlated with large artery stroke (LAS). However, no causal effect was found in LDL-C and apoB on LAS risk when we conducted mvMR. The IVW-MR also found a suggestive evidence that decreased LDL-C levels mediated by the PCSK9 (proprotein convertase subtilisin-kexin type 9) gene were associated with a reduced risk of any stroke (AS) (OR, 1.31; 95% CI, 1.13-1.52; p = 0.0003), any ischemic stroke (AIS) (OR, 1.29; 95% CI, 1.10-1.51; p = 0.001), and LAS (OR, 1.73; 95% CI, 1.15-2.59; p = 0.008), while NPC1L1 (Niemann-Pick C1-like protein)-mediated LDL-C levels were associated with a higher risk of small vessel stroke (SVS) (OR, 6.10; 95% CI, 2.13-17.43; p = 0.0008). The SMR revealed that expression of PCSK9 was associated with risk of AS (OR, 1.15; 95% CI, 1.03-1.28; p = 0.01), AIS (OR, 1.02; 95% CI, 1.14-1.29; p = 0.03), cardioembolic stroke (CES) (OR, 1.28; 95% CI, 1.01-1.61; p = 0.04). And, a significant association was found between the expression of NPC1L1 and the risk of SVS (OR, 1.15; 95% CI, 1.00-1.32; p = 0.04). Conclusion: We cautiously find that LDL-C and apoB was positively correlated with LAS. These findings suggest that the reducing LDL-C levels could be an effective prevention strategy for reducing the risk of stroke.

Mammalian Cell-Line-Expressed CD2v Protein of African Swine Fever Virus Provides Partial Protection against the HLJ/18 Strain in the Early Infection Stage.

A cell line expressing the CD2v protein of ASFV was generated. The efficient expression of CD2v protein was determined by immunofluorescence and Western blotting. The CD2v protein was Ni-affinity purified from the supernatant of cell cultures. The CD2v-expressing cells showed properties of hemadsorption, and the secreted CD2v protein exhibited hemagglutinating activity. The antigenicity and immunoprotection ability of CD2v were evaluated by immunizing pigs alone, combined with a cell-line-expressed p30 protein or triple combined with p30 and K205R protein. Immunized pigs were challenged with the highly virulent ASFV strain HLJ/18. Virus challenge results showed that CD2v immunization alone could provide partial protection at the early infection stage. Protein p30 did not show synergistic protection effects in immunization combined with CD2v. Interestingly, immunization with the triple combination of CD2V, p30 and K205R reversed the protection effect. The viremia onset time was delayed, and one pig out of three recovered after the challenge. The pig recovered from ASFV clinical symptoms, the rectal temperature returned to normal levels and the viremia was cleared. The mechanism of this protection effect warrants further investigation.

Optical trapping of microparticles with two tilted-focused laser beams.

We present an optical method for the manipulation of microparticles using two tilted-focused beams. First, the action on the microparticles is studied with a single tilted-focused beam. The beam is used to drive the directional motion of a dielectric particle. When the optical scattering force is larger than the optical gradient force, the particle is pushed to the tilted side of the optical axis by the optical force. Second, two tilted-focused beams with the same power and complementary tilt angles are used to assemble an optical trap. The trap can be used to realize the optical trapping of the dielectric particles and opto-thermal trapping of the light absorbing particles. The trapping mechanism is the balance of the forces exerted on the particles, including the optical scattering force, optical gradient force, gravity, and thermal gradient force. The trap center is away from the focal spots, which effectively prevents the laser beam from being focused on the trapped object.

Neutralizing antibody levels associated with injectable and aerosolized Ad5-nCoV boosters and BA.2 infection.

BACKGROUND: Several COVID-19 vaccines are in widespread use in China. Few data exist on comparative immunogenicity of different COVID-19 vaccines given as booster doses. We aimed to assess neutralizing antibody levels raised by injectable and inhaled aerosolized recombinant adenovirus type 5 (Ad5)-vectored COVID-19 vaccine as a heterologous booster after an inactivated COVID-19 vaccine two-dose primary series. METHODS: Using an open-label prospective cohort design, we recruited 136 individuals who had received inactivated vaccine primary series followed by either injectable or inhaled Ad5-vectored vaccine and measured neutralizing antibody titers against ancestral SARS-CoV-2 virus and Omicron BA.1 and BA.5 variants. We also measured neutralizing antibody levels in convalescent sera from 39 patients who recovered from Omicron BA.2 infection. RESULTS: Six months after primary series vaccination, neutralizing immunity against ancestral SARS-CoV-2 was low and neutralizing immunity against Omicron (B.1.1.529) was lower. Boosting with Ad5-vectored vaccines induced a high immune response against ancestral SARS-CoV-2. Neutralizing responses against Omicron BA.5 were ≥ 80% lower than against ancestral SARS-CoV-2 in sera from prime-boost subjects and in convalescent sera from survivors of Omicron BA.2 infection. Inhaled aerosolized Ad5-vectored vaccine was associated with greater neutralizing titers than injectable Ad5-vectored vaccine against ancestral and Omicron SARS-CoV-2 variants. CONCLUSIONS: These findings support the current strategy of heterologous boosting with injectable or inhaled Ad5-vectored SARS-CoV-2 vaccination of individuals primed with inactivated COVID-19 vaccine.

Revitalizing myocarditis treatment through gut microbiota modulation: unveiling a promising therapeutic avenue.

Numerous studies have demonstrated that gut microbiota plays an important role in the development and treatment of different cardiovascular diseases, including hypertension, heart failure, myocardial infarction, arrhythmia, and atherosclerosis. Furthermore, evidence from recent studies has shown that gut microbiota contributes to the development of myocarditis. Myocarditis is an inflammatory disease that often results in myocardial damage. Myocarditis is a common cause of sudden cardiac death in young adults. The incidence of myocarditis and its associated dilated cardiomyopathy has been increasing yearly. Myocarditis has gained significant attention on social media due to its association with both COVID-19 and COVID-19 vaccinations. However, the current therapeutic options for myocarditis are limited. In addition, little is known about the potential therapeutic targets of myocarditis. In this study, we review (1) the evidence on the gut-heart axis, (2) the crosslink between gut microbiota and the immune system, (3) the association between myocarditis and the immune system, (4) the impact of gut microbiota and its metabolites on myocarditis, (5) current strategies for modulating gut microbiota, (6) challenges and future directions for targeted gut microbiota in the treatment of myocarditis. The approach of targeting the gut microbiota in myocarditis is still in its infancy, and this is the study to explore the gut microbiota-immune system-myocarditis axis. Our findings are expected to pave the way for the use of gut microbiota as a potential therapeutic target in the treatment of myocarditis.