The correlation between gut microbiome and atrial fibrillation: pathophysiology and therapeutic perspectives.

Regulation of gut microbiota and its impact on human health is the theme of intensive research. The incidence and prevalence of atrial fibrillation (AF) are continuously escalating as the global population ages and chronic disease survival rates increase; however, the mechanisms are not entirely clarified. It is gaining awareness that alterations in the assembly, structure, and dynamics of gut microbiota are intimately engaged in the AF progression. Owing to advancements in next-generation sequencing technologies and computational strategies, researchers can explore novel linkages with the genomes, transcriptomes, proteomes, and metabolomes through parallel meta-omics approaches, rendering a panoramic view of the culture-independent microbial investigation. In this review, we summarized the evidence for a bidirectional correlation between AF and the gut microbiome. Furthermore, we proposed the concept of "gut-immune-heart" axis and addressed the direct and indirect causal roots between the gut microbiome and AF. The intricate relationship was unveiled to generate innovative microbiota-based preventive and therapeutic interventions, which shed light on a definite direction for future experiments.

A port statistics-based generic ballast water estimation and risk assessment approach and its application to Chinese ports.

The Ballast Water Management Convention now enters the experience-building stage, but developing countries have no adequate ballast water information yet. Against this background, considering the richness and generality of common port statistics, we develop a new generic approach to estimate discharge volumes and assess associated risks. This is one of the few efficient and feasible ways for port authorities to manage real discharged ballast water. Discharge volumes during 2017-2020 and risks in 2017 are analyzed for bulker and tanker. Results show that: (1) Ports in Yangtze River Delta and Bohai Rim received most ballast water, especially Ningbo-Zhoushan port as high-risk region receiving about 65 million tons per year; (2) With a higher ratio of discharge volumes to cargo throughputs, the tanker tends to release more ballast water than the bulker; (3) Chinese ports suffer more than 0.9 of the probability of non-indigenous species introduction. All these findings help implement convention globally.

Nanosecond pulse effectively ablated hepatocellular carcinoma with alterations in the gut microbiome and serum metabolites.

Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death in the world. Nanosecond pulsed electric fields (nsPEFs) have emerged as a new treatment for cancer. This study aims to identify the effectiveness of nsPEFs in the treatment of HCC and analyze the alterations in the gut microbiome and serum metabonomics after ablation. Methods: C57BL/6 mice were randomly divided into three groups: healthy control mice (n = 10), HCC mice (n = 10), and nsPEF-treated HCC mice (n = 23). Hep1-6 cell lines were used to establish the HCC model in situ. Histopathological staining was performed on tumor tissues. The gut microbiome was analyzed by 16S rRNA sequencing. Serum metabolites were analyzed by liquid chromatography-mass spectrometry (LC-MS) metabolomic analysis. Spearman's correlation analysis was carried out to analyze the correlation between the gut microbiome and serum metabonomics. Results: The fluorescence image showed that nsPEFs were significantly effective. Histopathological staining identified nuclear pyknosis and cell necrosis in the nsPEF group. The expression of CD34, PCNA, and VEGF decreased significantly in the nsPEF group. Compared with normal mice, the gut microbiome diversity of HCC mice was increased. Eight genera including Alistipes and Muribaculaceae were enriched in the HCC group. Inversely, these genera decreased in the nsPEF group. LC-MS analysis confirmed that there were significant differences in serum metabolism among the three groups. Correlation analysis showed crucial relationships between the gut microbiome and serum metabolites that are involved in nsPEF ablation of HCC. Conclusion: As a new minimally invasive treatment for tumor ablation, nsPEFs have an excellent ablation effect. The alterations in the gut microbiome and serum metabolites may participate in the prognosis of HCC ablation.

A Novel Predictor of Pathologic Complete Response for Neoadjuvant Immunochemotherapy in Resectable Locally Advanced Esophageal Squamous Cell Carcinoma.

Purpose: Neoadjuvant immunochemotherapy (nICT) for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) has attracted widespread attention recently, whose safety and clinical benefit was observed in clinical researches. This study aimed to develop and validate a novel predictor systemic inflammation-tumor markers index (SITI) to predict the pathological complete response (pCR) for resectable LA-ESCC patients receiving nICT. Patients and Methods: A total of 147 LA-ESCC patients who underwent nICT followed by surgery from February 2020 to April 2022 were included in the study. The dynamic change of inflammatory indexes was compared at baseline, after two cycles of nICT and postoperative one month. Least absolute shrinkage and selection operator (LASSO) regression was performed to avoid collinearity and identify key indexes, with SITI constructed. After univariate and multivariate stepwise forward logistic analyses, a nomogram for pCR prediction was developed. Results: 41(27.9%) patients achieved pCR among 147 resectable LA-ESCC patients received nICT. Compared with baseline, most inflammatory indexes were significantly decreased at postoperative one month. 5 key indexes were identified and then a predictive index named SITI was constructed. The result showed that lower SITI and earlier clinical tumor node metastasis (cTNM) stage were more likely to achieve pCR. The nomogram for pCR prediction had excellent discrimination performance (C-index = 0.791). Conclusion: The SITI is an independent predictor for pCR in resectable LA-ESCC patients received nICT. To our knowledge, our nomogram is the first model using systemic inflammation-tumor markers for pCR prediction and may be a promising predictor to effectively differentiate pCR for nICT in LA-ESCC patients.

Portfolio value-at-risk estimation for spot chartering decisions under changing trade patterns: A copula approach.

Evolving geopolitical relationships between countries (especially between China and the United States) in recent years have highlighted dynamically changing trade patterns across the globe, all of which elevate risk and uncertainty for transport service providers. In order to mitigate risks, shipowners and operators must be able to estimate risks appropriately; one potentially promising method of doing so is through the value-at-risk (VaR) method. VaR describes the worst loss a portfolio is likely to sustain, which will not be exceeded over a target time horizon at a given level of confidence. This article proposes a copula-based GARCH model to estimate the joint multivariate distribution, which is a key component in VaR estimation. We show that the copula model can capture the VaR more successfully, as compared with the traditional method of calculation. As an empirical study, the expected portfolio VaR is examined when a shipowner chooses among Panamax soybean trading routes under a condition of reduced trade volumes between the United States and China due to the ongoing trade turmoil. This study serves as one of the very few papers in the literature on shipping portfolio VaR analysis. The results have significant implications for shipowners regarding fleet repositioning, decision making, and risk management.

Quantifying the impact of pandemic lockdown policies on global port calls.

The recent experience of lockdowns during COVID-19 highlights the prolonged impact a pandemic could have on ports and the shipping industry. This paper uses port call data derived from the Automatic Identification System (AIS) reports from the world's 30 largest container ports to quantify both the immediate and longer-term impact of national COVID-19 lockdown policies on global shipping flows. The analysis uses the Difference-in-Difference (DID) and combined regression discontinuity design (RDD)-DID models to represent the effects of lockdown policies. The combination of RDD and DID models is particularly effective because it can mitigate time trends in the data, e.g., the Chinese New Year effect on Chinese ports. This study further examines the potential shock propagation effects, namely, how lockdown policy in one country (i.e., China) can affect the number of port calls in other countries. We categorize ports in other countries into a high-connectivity (with Chinese ports) group and a low-connectivity group, using a proposed connectivity index with China derived from individual vessel trajectories obtained from the AIS data. The results provide a clearly measurable picture of the kinds of trade shocks and consequent pattern changes in port calls over time caused by responses to lockdown policies of varying levels of stringency. We further document the existence of significant shock propagation effects. As the risk of pandemics rises in the twenty-first century, these results can be used by policy makers to assess the potential impact of different levels of lockdown policy on the maritime industry and trade flows more broadly. Maritime players can also use findings such as these to manage their capacity during lockdowns more effectively and to respond more flexibly to changing demand in seaborne transportation.

Identification and Verification of Potential Core Genes in Pediatric Septic Shock.

BACKGROUND: Septic shock is a frequent and costly problem among patients in the pediatric intensive care unit (PICU) and is associated with high mortality and devastating survivor morbidity. In this study, we aimed to screen candidate biomarkers and potential therapeutic targets for septic shock. METHODS: GSE26440 dataset was downloaded from Gene Expression Omnibus (GEO), including 32 normal controls and 98 children with septic shock RNA samples from whole blood. The pathways and functional annotations of differentially expressed genes (DEGs) in the two types of samples were examined by GO and KEGG pathway enrichment analyses using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) tool. Protein-protein interactions (PPI) of the above-described DEGs were investigated using the Search Tool for the Retrieval of Interacting Genes (STRING) and Hub gene identification was performed by the plug-in cytoHubba in Cytoscape software. RESULTS: A total of 140 genes were identified as DEGs, of which 98 genes were up-regulated and 42 genes were down-regulated. GO function analysis showed that DEGs were significantly enriched in biological processes, including immune response, leukocyte activation involved in immune response, and so on. The top hub genes, namely MMP9, CEACAM8, ARG1, MCEMP1, LCN2, RETN, S100A12, GPR97, and TRAT1 were recognized from the protein-protein interaction (PPI) network. Furthermore, qRT-PCR results demonstrated that the mRNA level of MMP9, CEACAM8, ARG1, MCEMP1, LCN2, RETN, and S100A12 was elevated while GPR97 was decreased in involved mouse and human models. However, TRAT1 expression is species-dependent which was decreased in the mouse septic shock model but elevated in the human LPS-treated macrophages model. CONCLUSION: Taken together, the identification and validation of several novel hub genes, especially GPR97 and TRAT1, deepen our comprehension of the molecular mechanisms of septic shock progression. These genes may be therapeutic molecular targets or diagnostic biomarkers in patients with septic shock.

Sacubitril/Valsartan contributes to improving the diabetic kidney disease and regulating the gut microbiota in mice.

Background: Diabetic kidney disease (DKD), as a serious microvascular complication of diabetes, has limted treatment options. It is reported that the Sacubitril/Valsartan (Sac/Val) can improve kidney function, and the disordered gut microbiota and part of its metabolites are related to the development of DKD. Therefore, we aim to explore whether the effect of Sac/Val on DKD is associated with the gut microbiota and related plasma metabolic profiles. Methods: Male C57BL/6J mice were randomly divided into 3 groups: Con group (n = 5), DKD group (n = 6), and Sac/Val group (n = 6) . Sac/Val group was treated with Sac/Val solution. The intervention was given once every 2 days for 6 weeks. We measured the blood glucose and urine protein level of mice at different times. We then collected samples at the end of experiment for the 16s rRNA gene sequencing analysis and the untargeted plasma metabonomic analysis. Results: We found that the plasma creatinine concentration of DKD-group mice was significantly higher than that of Con-group mice, whereas it was reduced after the Sac/Val treatment. Compared with DKD mice, Sac/Val treatment could decrease the expression of indicators related to EndMT and renal fibrosis like vimentin, collagen IV and fibronectin in kidney. According to the criteria of LDA ≥ 2.5 and p<0.05, LefSe analysis of gut microbiota identified 13 biomarkers in Con group, and 33 biomarkers in DKD group, mainly including Prevotella, Escherichia_Shigella and Christensenellaceae_R_7_group, etc. For the Sac/Val group, there were 21 biomarkers, such as Bacteroides, Rikenellaceae_RC9_gut_group, Parabacteroides, Lactobacillus, etc. Plasma metabolomics analysis identified a total of 648 metabolites, and 167 important differential metabolites were screened among groups. KEGG pathway of tryptophan metabolism: M and bile secretion: OS had the highest significance of enrichment. Conclusions: Sac/Val improves the renal function of DKD mice by inhibiting renal fibrosis. This drug can also regulate gut microbiota in DKD mice.

The psychology of cruise service usage post COVID-19: Health management and policy implications.

The cruise industry has suffered a huge loss due to the suspension of cruise operations during the COVID-19 pandemic. As the industry is preparing for recovery, there is an urgent need for research on cruise consumers' psychology, in particular, the factors influencing their intention to use cruise services after the pandemic. This study employs theories, namely, the health belief model, trust theory and attitude theory, to investigate consumers' use intention for cruise services after the pandemic. An online survey was administered to consumers in China's tourism industry, where 376 responses were received. Subsequently, this study employs structural equation modelling to test its theoretical model consisting of hypotheses. The results show that consumers' trust is directly influenced by health belief constructs including perceived safety threat, outcome expectation, self-efficacy and cues to action. Next, trust exerts a direct impact on consumers' attitude and intention to use cruise services. Moreover, this study finds full and partial mediation effects. The findings provide a series of recommendations for cruise operators and policymakers in terms of marketing strategies, service design, public communication and health measures.

Cruise transport service usage post COVID-19: The health belief model application.

This study investigates the key psychological factors that influence customer's intention to use cruise services post COVID-19. A theoretical model grounded on consumer and health-driven theories (i.e. perceived value, perceived trust and health belief model) is developed. A survey questionnaire is designed and administered to 376 Chinese consumers. The theoretical model was tested via structural equation modelling. Results reveal that the constructs of the health belief model (i.e. perceived benefits, perceived health threat, self-efficacy and cues to action) have a significant effect on customers' perceived value towards cruise services. Perceived value then has direct and indirect effects on customers' cruise intention through perceived trust. This study enhances academic research by justifying customers' intention to use cruise services via consumer and health-belief viewpoints and provides implications for cruise management and policy formulation.