Design, Synthesis, and Evaluation of 8-(o-Tolyl)quinazoline Derivatives as Small-Molecule PD-1/PD-L1 Antagonists.

Small-molecule inhibitors targeting programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) interactions can compensate for the shortcomings of antibody-based inhibitors and have attracted considerable attention, some of which have already entered clinical trials. Herein, based on our previous study on small-molecule PD-L1 inhibitors, we reported a series of 8-(o-tolyl)quinazoline derivatives by the skeleton merging strategy. Homogenous time-resolved fluorescence (HTRF) assay against PD-1/PD-L1 interaction identified compound A5, which showed the most potent inhibition with an IC50 value of 23.78 nM. Meanwhile, based on the results of HTRF assay, the structure-activity relationships (SARs) of the tail were focused on. Cell-based PD-1/PD-L1 blockade assay further revealed that A5 significantly blocked the PD-1/PD-L1 interaction at 1.1 µM in the co-culture system of Jurkat-NFAT-PD-1 cells and Hep3B-OS8-hPD-L1 cells with no significant cytotoxicity on Jurkat cells. Moreover, the proposed binding mode of A5 was investigated by a docking analysis. These results indicate that compound A5 is a promising lead compound that deserves further investigation.

Integrated microbiome and metabolome analyses reveal the effects of low pH on intestinal health and homeostasis of crayfish (Procambarus clarkii).

Low pH (LpH) poses a significant challenge to the health, immune response, and growth of aquatic animals worldwide. Crayfish (Procambarus clarkii) is a globally farmed freshwater species with a remarkable adaptability to various environmental stressors. However, the effects of LpH stress on the microbiota and host metabolism in crayfish intestines remain poorly understood. In this study, integrated analyses of antioxidant enzyme activity, histopathological damage, 16S rRNA gene sequencing, and liquid chromatography-mass spectrometry (LC-MS) were performed to investigate the physiology, histopathology, microbiota, and metabolite changes in crayfish intestines exposed to LpH treatment. The results showed that LpH stress induced obvious changes in superoxide dismutase and catalase activities and histopathological alterations in crayfish intestines. Furthermore, 16S rRNA gene sequencing analysis revealed that exposure to LpH caused significant alterations in the diversity and composition of the crayfish intestinal microbiota at the phylum and genus levels. At the genus level, 14 genera including Bacilloplasma, Citrobacter, Shewanella, Vibrio, RsaHf231, Erysipelatoclostridium, Anaerorhabdus, Dysgonomonas, Flavobacterium, Tyzzerella, Brachymonas, Muribaculaceae, Propionivibrio, and Comamonas, exhibited significant differences in their relative abundances. The LC-MS analysis revealed 859 differentially expressed metabolites in crayfish intestines in response to LpH, including 363 and 496 upregulated and downregulated metabolites, respectively. These identified metabolites exhibited significant enrichment in 24 Kyoto Encyclopedia of Genes and Genomes pathways (p < 0.05), including seven and 17 upregulated and downregulated pathways, respectively. These pathways are mainly associated with energy and amino acid metabolism. Correlation analysis revealed a strong correlation between the metabolites and intestinal microbiota of crayfish during LpH treatment. These findings suggest that LpH may induce significant oxidative stress, intestinal tissue damage, disruption of intestinal microbiota homeostasis, and alterations in the metabolism in crayfish. These findings provide valuable insights into how the microbial and metabolic processes of crayfish intestines respond to LpH stress.

Epidemiological investigation and ß-lactam antibiotic resistance of Riemerella anatipestifer isolates with waterfowl origination in Anhui Province, China.

Riemerella anatipestifer (R. anatipestifer) is a highly pathogenic and complex serotypes waterfowl pathogen with inherent resistance to multiple antibiotics. This study was aimed to investigate the antibiotic resistance characteristics and genomic features of R. anatipestifer isolates in Anhui Province, China in 2023. A total of 287 cases were analysed from duck farms and goose farms, and the R. anatipestifer isolates were subjected to drug resistance tests for 30 antimicrobials. Whole genome sequencing (WGS) and bioinformatics analysis were performed on the bacterial genomes, targeting the ß-lactam resistance genes. The results showed that a total of 74 isolates of R. anatipestifer were isolated from 287 cases, with a prevalence of 25.8%. The antimicrobial susceptibility testing (AST) revealed that all the 74 isolates were resistant to multiple drugs, ranging from 13 to 26 kinds of drugs. Notably, these isolates showed significant resistance to aminoglycosides and macrolides, which are also commonly used in clinical practices. Data revealed the presence of several ß-lactamase-related genes among the isolates, including a novel blaRASA-1 variant (16.2%), the class A extended-spectrum ß-lactamase blaRAA-1 (12.2%), and a blaOXA-209 variant (98.6%). Functional analysis of the variants blaRASA-1 and blaOXA-209 showed that the blaRASA-1 variant exhibited activity against various ß-lactam antibiotics while their occurrence in R. anatipestifer were not common. The blaOXA-209 variant, on the other hand, did not perform any ß-lactam antibiotic resistance. Furthermore, we observed that blaRAA-1 could undergo horizontal transmission among different bacteria via the insertion sequence IS982. In conclusion, this study delves into the high prevalence of R. anatipestifer infection in waterfowl in Anhui, China. The isolated strains exhibit severe drug resistance issues, closely associated with the prevalence of antibiotic resistance genes (ARG). Additionally, our research investigates the ß-lactam antibiotic resistance mechanism in R. anatipestifer.

Effects of Habitual Dietary Change on the Gut Microbiota and Health of Silkworms.

Diet plays a crucial role in shaping the gut microbiota and overall health of animals. Traditionally, silkworms are fed fresh mulberry leaves, and artificial diets do not support good health. The aim of this study was to explore the relationship between the dietary transition from artificial diets to mulberry leaves and the effects on the gut microbiota and physiological changes in silkworms as a model organism. With the transition from artificial diets to mulberry leaves, the diversity of the silkworm gut microbiota increased, and the proportion of Enterococcus and Weissella, the dominant gut bacterial species in silkworms reared on artificial diets, decreased, whereas the abundance of Achromobacter and Rhodococcus increased. Dietary transition at different times, including the third or fifth instar larval stages, resulted in significant differences in the growth and development, immune resistance, and silk production capacity of silkworms. These changes might have been associated with the rapid adaptation of the intestinal microbiota of silkworms to dietary transition. This study preliminarily established a dietary transition-gut microbial model in silkworms based on the conversion from artificial diets to mulberry leaves, thus providing an important reference for future studies on the mechanisms through which habitual dietary changes affect host physiology through the gut microbiome.

Experimental evidence of effective disinfectant to control the transmission of Micropterus salmoides rhabdovirus.

Micropterus salmoides rhabdovirus (MSRV) is a significant pathogen that causes high morbidity and mortality in largemouth bass, leading to enormous economic losses for largemouth bass aquaculture in China. The aim of this study was to investigate the efficacy of four disinfectants (potassium permanganate, glutaraldehyde, trichloroisocyanuric acid and povidone iodine) on MSRV, to control the infection and transmission of MSRV in largemouth bass aquaculture. The disinfectants were tested at different concentrations (5, 25, 50, 100 and 500 mg/L) prepared with distilled water for 30 min contact time, and the viral nucleic acid was quantified using qPCR and the infectivity was tested by challenge experiment. Potassium permanganate at 5-500 mg/L, glutaraldehyde at 500 mg/L, trichloroisocyanuric acid at 50-500 mg/L and povidone iodine at 500 mg/L concentration could effectively decrease the virus nucleic acid, and the survival rate of largemouth bass juveniles after challenge experiment increased significantly from 3.7% ± 6.41% to 33.33 ± 11.11% - 100%. Moreover, the minimum effective time of 5 mg/L potassium permanganate was further studied at 2, 5, 10 and 20 min contact time. The viral nucleic acid decreased significantly at 5-20 min exposure time, and the survival rate increased significantly from 7.41% ± 6.41% to 77.78 ± 11.11% - 100%. The median lethal concentration (LC50 ) values of potassium permanganate were 10.64, 6.92 and 3.7 mg/L at 24, 48 and 96 h, respectively. Potassium permanganate could be used for the control of MSRV in the cultivation process; the recommended concentration is 5 mg/L and application time should be less than 24 h. The results could be applied to provide a method to control the infection and transmission of MSRV in water, and improve the health status of largemouth bass.

Use of intracardiac echocardiography in vein of Marshall ethanol infusion for ablation of persistent atrial fibrillation.

BACKGROUND: Few methods have been reported to demonstrate real-time effects during vein of Marshall (VOM) ethanol infusion in persistent atrial fibrillation (PeAF). OBJECTIVE: This study was to evaluate the impact of left atrial (LA) monitoring using intracardiac echocardiography (ICE) during VOM ethanol infusion. METHODS: Seventy-four consecutive patients with PeAF who underwent VOM ethanol infusion followed by radiofrequency (RF) ablation were included. Patients with findings on ICE consistent with echogenic streaming in the LA and with increased myocardial local echogenicity along the VOM area were placed into one group (group A) and those without into the other group (group B). Outcomes between the 2 groups were compared. RESULTS: Forty-six patients (62%) were placed into group A. A new ethanol-induced low-voltage area in group A was larger than that in group B (8.5 cm2 [5.5-10.2 cm2] and 4.0 cm2 (2.4-6.3 cm2]; P < .001). The RF ablation time required to achieve MI block was reduced in group A patients (263.0 seconds [196.0-351.0 seconds] vs 417.0 seconds [315.0-709.5 seconds] in group B patients; P < .001). MI block was achieved in 46 patients (100%) via an endocardial approach in group A and 27 patients (96.4%) in group B (extra coronary sinus ablation in 4 patients). One patient developed clinically significant pericardial effusions and required pericardiocentesis in group B. CONCLUSION: Presence of increased myocardial local echogenicity at the ridge and consistent echogenic streaming in the LA detected by ICE-based imaging during VOM ethanol infusion suggests increased ablated tissue in that region and lower RF ablation time during ablation for PeAF.

Effects of 3-month dapagliflozin on left atrial function in treatment-naïve patients with type 2 diabetes mellitus: Assessment using 4-dimensional echocardiography.

BACKGROUND: The sodium-glucose transporter-2 (SGLT-2) inhibitor dapagliflozin can improve left ventricular (LV) performance in patients with type 2 diabetes mellitus (T2DM). However, the effects on left atrial (LA) function in treatment-naïve T2DM patients remain unclear. The aim of our study was 1) to investigate the effects of 3-month treatment with dapagliflozin on LA function in treatment-naïve patients with T2DM using 4-dimensional automated LA quantification (4D Auto LAQ) and 2) to explore linked covariation patterns of changes in clinical and LA echocardiographic variables. METHODS: 4D Auto LAQ was used to evaluate LA volumes, longitudinal and circumferential strains in treatment-naïve T2DM patients at baseline, at follow-up, and in healthy control (HC). Sparse canonical correlation analysis (sCCA) was performed to capture the linked covariation patterns between changes in clinical and LA echocardiographic variables within the treatment-naïve T2DM patient group. RESULTS: This study finally included 61 treatment-naïve patients with T2DM without cardiovascular disease and 39 healthy controls (HC). Treatment-naïve T2DM patients showed reduced LA reservoir and conduit function at baseline compared to HC, independent of age, sex, BMI, and blood pressure (LASr: 21.11 ± 5.39 vs. 27.08 ± 5.31 %, padjusted = 0.017; LAScd: -11.51 ± 4.48 vs. -16.74 ± 4.51 %, padjusted = 0.013). After 3-month treatment with dapagliflozin, T2DM patients had significant improvements in LA reservoir and conduit function independent of BMI and blood pressure changes (LASr: 21.11 ± 5.39 vs. 23.84 ± 5.74 %, padjusted < 0.001; LAScd: -11.51 ± 4.48 vs. -12.75 ± 4.70 %, padjusted < 0.001). The clinical and LA echocardiographic parameters showed significant covariation (r = 0.562, p = 0.039). In the clinical dataset, changes in heart rate, insulin, and BMI were most associated with the LA echocardiographic variate. In the LA echocardiographic dataset, changes in LAScd, LASr, and LASr_c were most associated with the clinical variate. CONCLUSION: Compared with HC, treatment-naïve patients with T2DM had lower LA function, and these patients benefited from dapagliflozin administration, particularly in LA function.

Intracardiac echocardiography is a promising strategy for guiding closure of the left atrial appendage.

Background and Aims: Percutaneous transcatheter left atrial appendage (LAA) closure (LAAC) is an effective approach for preventing ischemic stroke in nonvalvular atrial fibrillation patients. Intracardiac echocardiography (ICE), a new imaging modality, is a promising strategy for guiding LAAC. This review highlights the various strategies for ICE-guided-LAAC as an option for clinical policy. Methods: A comprehensive literature search was conducted of PubMed, ScienceDirect, Ovid Web of Science, SpringerLink, and other notable databases to identify recent peer-reviewed clinical trials, reviews, and research articles related to ICE and its application in the guidance of LAAC. Results: Various methods are used to evaluate the spatial structure and dimensions of the LAA. The main techniques for guiding LAAC are transesophageal echocardiography (TEE), cardiac computed tomography (CTA), and ICE. Among these techniques, the advantages of ICE typically include (1) multiangle and real-time assessment of intracardiac structure, (2) a reduction in procedural fluoroscopy, (3) reduced operation time and improved workflow in the catheterization laboratory, and (4) the avoidance of general anesthesia and the early detection of complications. Conclusion: ICE is a promising strategy for the guidance of LAAC. Among the most advanced and recent technological innovations in cardiovascular imaging in general and volume imaging in particular, ICE offers greater efficacy and safety.

Association between impaired renal function and subclinical myocardial dysfunction in patients with heart failure with preserved ejection fraction: assessment using noninvasive pressure-strain loop.

PURPOSE: To evaluate the abnormal myocardial function in HFpEF patients with renal dysfunction and investigate the relationship between renal function and myocardial mechanical characteristics in patients with HFpEF. METHODS: 134 patients with HFpEF and 32 control subjects were enrolled in our study. Clinical and echocardiography data were collected for offline analysis. Global work index(GWI), global constructive work(GCW), global waste work(GWW), and global work efficiency(GWE) were measured after non-invasive pressure strain loop analysis. Univariate and multivariate analyses were used to determine the correlation between renal function and myocardial function in patients with HFpEF. RESULTS: In comparison to control subjects, patients with HFpEF tend to have higher GWW(78[50-115] vs 108[65-160] mmHg%, P<0.05) and lower GWE(96[95-97] vs 95[92-96] %, P<0.05) while LVEF(65.5±3.3 vs 64.3±4.6 %, P<0.05) were comparable between them. Besides, increased GWW(86[58-152] vs 125[94-187] mmHg%, P<0.05) and decreased GWE(96[93-97] vs 94[92-96] %, P<0.05) were detected in patients with renal dysfunction compared to those with normal renal function. An independent correlation was found between eGFR and GWW after multivariate analysis. CONCLUSIONS: The more severely impaired myocardial function was detected in HFpEF patients with renal dysfunction compared to those with normal renal function. eGFR was independently correlated to GWW in patients with HFpEF.

Comparative Transcriptomic Analysis of Largemouth Bass (Micropterus salmoides) Livers Reveals Response Mechanisms to High Temperatures.

High temperatures are considered one of the most significant limitations to subtropical fishery production. Largemouth bass (Micropterus salmoides) is an economically important freshwater species grown in subtropical areas, which are extremely sensitive to heat stress (HS). However, comprehensive transcriptomic data for the livers of largemouth bass in response to HS are still lacking. In this study, a comparative transcriptomic analysis was performed to investigate the gene expression profiles of the livers of largemouth bass under HS treatment. As a result, 6114 significantly differentially expressed genes (DEGs), which included 2645 up-regulated and 3469 down-regulated genes, were identified in response to HS. Bioinformatics analyses demonstrated that the 'ECM-receptor interaction' pathway was one of the most dramatically changed pathways in response to HS, and eight DEGs assigned to this pathway were taken as hub genes. Furthermore, the expression of these eight hub genes was determined by quantitative reverse transcription PCR, and all of them showed a significant change at the transcriptional level, suggesting a crucial role of the 'ECM-receptor interaction' pathway in the response of largemouth bass to HS. These findings may improve our understanding of the molecular mechanisms underlying the response of largemouth bass to HS.

Japanese encephalitis virus NS4B inhibits interferon beta production by targeting TLR3 and TRIF.

Japanese encephalitis virus (JEV) is a flavivirus transmitted by mosquitoes, causing epidemics of encephalitis in humans and reproductive disorders in pigs. This virus is predominantly distributed in Asian countries and causes tens of thousands of infections in humans annually. Interferon (IFN) is an essential component of host defense against viral infection. Multiple studies have indicated that multifunctional nonstructural proteins of flaviviruses suppress the host IFN response via various strategies to facilitate viral replication. The flaviviruses encoded nonstructural protein 4B (NS4B) is a multifunctional hydrophobic nonstructural protein widely involved in viral replication, pathogenesis and host immune evasion. In this study, we demonstrated that NS4B of JEV suppressed the induction of IFN-ß production, mainly through targeting the TLR3 and TRIF (a TIR domain-containing linker that induces IFN-ß) proteins in the TLR3 pathway. In a dual-luciferase reporter assay, JEV NS4B significantly inhibited the activation of IFN-ß promoter induced by TLR3 and simultaneously treated with poly (I:C). Moreover, NS4B also inhibited the activation of IFN-ß promoter triggered by interferon regulatory factor 3 (IRF3)/5D or its upstream molecules in TLR3 signaling pathway. Furthermore, NS4B inhibited the phosphorylation of IRF3 under the stimulation of TLR3 and TRIF molecules. Mechanistically, JEV NS4B interacts with TLR3 and TRIF and confirmed by co-localization and co-immunoprecipitation assay, thereby inhibiting the activation of downstream sensors in the TLR3-mediated pathway. Overall, our results provide a novel mechanism by which JEV NS4B interferes with the host's antiviral response through targeting TLR3 receptor signaling pathway.

Spatial Patterns of Planktonic Fungi Indicate Their Potential Contributions to Biological Carbon Pump and Organic Matter Remineralization in the Water Column of South China Sea.

Fungi have long been known to be dynamic in coastal water columns with multiple trophic modes. However, little is known about their interactions with abiotic and biotic components, contribution to the biological carbon pump (BCP), and organic matter remineralization in the oceanic water column. In this study, we investigated how fungi vary spatially and how their variations relate to that of bacteria in the water column of the South China Sea (SCS). Fungi were about three orders less prevalent than bacteria, and the main factors influencing their distribution were depth, temperature, and distance from the sites of riverine inputs. The decline in the abundance of fungi with depth was less steep than that of bacteria. Correlation tests revealed a strong positive association between the abundance of fungi and bacteria, especially in the twilight (r = 0.62) and aphotic (r = 0.70) zones. However, the co-occurrence network revealed mutual exclusion between certain members of fungi and bacteria. The majority of fungi in the water column were saprotrophs, which indicated that they were generally involved in the degradation of organic matter, particularly in twilight and aphotic zones. Similar to bacteria, the involvement of fungi in the metabolism of carbohydrates, proteins, and lipids was predicted, pointing to their participation in the turnover of organic carbon and the biogeochemical cycling of carbon, nitrogen, and sulfur. These findings suggest that fungi play a role in BCP and support their inclusion in marine microbial ecosystem models.

The LIM Domain Protein BmFHL2 Inhibits Egg Production in Female Silkworm, Bombyx mori.

The female Bombyx mori accumulates a large amount of egg proteins, mainly Vg and 30K, during egg formation to provide nutrition for embryo development. The synthesis and transport of Vg have been extensively studied, particularly the regulation of Vg transcription induced by 20E; however, the mechanism of 30K protein synthesis is poorly studied. As a model organism of the order Lepidoptera, B. mori has high reproduction potential. In the present study, we found that the FHL2 homologous gene (BmFhl2) in B. mori is involved in inhibiting female egg formation by influencing the synthesis of 30K protein. Interference of BmFhl2 expression in silkworm females increased 30K protein synthesis, accelerated ovarian development, and significantly increased the number of eggs produced and laid; however, the 20E pathway was inhibited. The transcription levels of Vg and 30Kc19 were significantly downregulated following BmFhl2 overexpression in the silkworm ovarian cell line BmN. The Co-IP assay showed that the potential binding protein of BmFHL2 included three types of 30K proteins (30Kc12, 30Kc19, and 30Kc21). These results indicate that BmFHL2 participates in egg formation by affecting 30K protein in female B. mori.

Association between left ventricular geometry and global myocardial work in patients with heart failure with preserved ejection fraction: assessment using strain-pressure loop.

Concentric LV remodeling and hypertrophy are common structural abnormalities in patients with heart failure with preserved ejection fraction (HFpEF) and tend to be accompanied by impaired LV function. Assessment of global myocardial work (GMW) using strain-pressure loop may provide more comprehensive assessment of LV myocardial function, overcoming the limitations of the conventional parameters. We investigated the value of GMW in patients with HFpEF and assessed the relationship of GMW with concentric remodeling and hypertrophy. Consecutive patients with HFpEF (n = 107) and sex-matched healthy controls (n = 32) were prospectively enrolled. Clinical and conventional echocardiography variables were obtained. Further analyses of offline data were performed to obtain GMW indices including global work index (GWI), global constructive work (GCW), global waste work (GWW), and global work efficiency (GWE). Association of concentric remodeling and hypertrophy with GMW was analyzed by univariate and multivariate analysis. HFpEF patients showed lower GWE (94% vs 96%, P < 0.001) and higher GWW (114 mmHg% vs 78 mmHg%, P = 0.003) than control group, while GWI (2111 mmHg% vs 2146 mmHg%, P = 0.877) and GCW (2369 mmHg% vs 2469 mmHg%, P = 0.733) were comparable in the two groups. HFpEF patients with relative wall thickness (RWT) > 0.42 had reduced GWE (94% vs 95%, P = 0.034) compared to HFpEF patients with RWT ≤ 0.42, while GWI, GCW, and GWW were comparable between these two subgroups. Multivariate analysis showed an independent association of RWT with GWI, GCW, and GWE, respectively. Impaired global myocardial work was detected in patients with HFpEF. Impaired LV GMW may be associated with increased RWT.

The vertical transmission of Salmonella Enteritidis in a One-Health context.

Salmonella enterica serovar Enteritidis (S. Enteritidis, SE) is a foodborne zoonotic pathogen, causing economic losses in animal husbandry and large numbers of human deaths and critically threatening economic development and public health. Human infection with SE has complex transmission routes, involving the environment, animal reservoirs, and water in a One-Health context. Food-producing animals, particularly poultry and livestock, are regarded as the most common sources of SE infection in humans. However, there is little known about the vertical transmission of SE in a One-Health context. In this review, we analyze the ecological significance of SE in a One-Health context. Importantly, we focus on the difference in vertical transmission of SE in poultry, livestock, and humans. We introduce the transmission pathway, describe the immune mechanisms, and discuss the models that could be used for studying the vertical transmission of SE and the strategy that prevention and control for vertical transmission of SE into the future from a One-Health perspective. Together, considering the vertical transmission of SE, it is helpful to provide important insights into the control and decontamination pathways of SE in animal husbandry and enhance knowledge about the prevention of fetal infection in human pregnancy.

Respiratory control minimizes diaphragmatic contraction and dry cough during pulsed-field ablation of atrial fibrillation.

AIMS: Pulsed-field ablation (PFA) is a promising new ablation modality to treat atrial fibrillation. However, PFA can cause varying degrees of diaphragmatic contraction and dry cough, especially under conscious sedation. This prospective study presents a method to minimize the impact of PFA on diaphragmatic contraction and dry cough during the procedure. METHODS AND RESULTS: Twenty-eight patients underwent PFA for pulmonary vein (PV) and superior vena cava isolation under conscious sedation. Each patient received two groups of ablations in each vein: the control group allowed PFA application during any phase of respiratory cycle, while the test group used respiratory control, delivering PFA energy only at the end of expiration. A rating score system was developed to assess diaphragmatic contraction and dry cough. A total of 1401 control ablations and 4317 test ablations were performed. The test group had significantly lower scores for diaphragmatic contraction (P < 0.01) and dry cough (P < 0.001) in all PVs compared to the control group. The average relative reductions in scores for all PVs were 33-47% for diaphragmatic contraction and 67-83% for dry cough. The percentage of ablations with scores ≧2 for diaphragmatic contraction decreased significantly from 18.5-28.0% in the control group to 0.4-2.6% in the test group (P < 0.001). For dry cough, the percentage decreased from 11.9-43.7% in the control group to 0.7-2.1% in the test group. CONCLUSION: Pulsed-field ablation application at the end of expiration can reduce the severity of diaphragmatic contraction and eliminate moderate and severe dry cough during PV isolation performed under conscious sedation.

Subclinical left ventricular myocardial dysfunction in patients with obstructive sleep apnea syndrome: insights from noninvasive left ventricular myocardial work analysis.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is associated with various cardiovascular diseases and has aroused public concern. Early detection for declining myocardial function is of great significance. This study was aimed at noninvasively evaluating the subclinical left ventricular (LV) myocardial dysfunction with LV pressure-strain loop (PSL) in patients with OSAS having normal LV ejection fraction. METHODS: We enrolled 200 patients with OSAS who visited the Beijing Chaoyang Hospital between February 2021 and December 2021. According to the apnea-hypopnea index (AHI), patients were divided into mild, moderate, and severe groups. The global longitudinal strain (GLS) of the left ventricle was analyzed by two-dimensional speckle tracking echocardiography. The LV PSL was used to assess global work index (GWI), global constructive work (GCW), global waste work (GWW), and global work efficiency (GWE), and comparisons were made among groups. RESULTS: GLS was significantly lower in the severe group than in mild and moderate group. GWI, GCW, and GWE were lower in the severe group than in mild and moderate groups. GWW was significantly higher in the severe group than in the mild group. GLS, GWI, and GWE were moderately correlated with AHI (Spearman's ρ = -0.468, -0.321, and -0.319, respectively; P < 0.001), whereas GCW and GWW showed a weak correlation with AHI (Spearman's ρ = -0.226 and 0.255 respectively; P < 0.001). Multiple regression analyses revealed AHI was independently associated with GWI after adjusting for SBP, GLS, e', etc. AHI was independently associated with GCW after adjusting for SBP, GLS, etc. CONCLUSIONS: The LV PSL is a new technique to noninvasively detect myocardial function deterioration in patients with OSAS and preserved LV ejection fraction. Increased severity of OSAS was independent associated with both decreased GWI and GCW.

Regulatory Mechanisms between Quorum Sensing and Virulence in Salmonella.

Salmonella is a foodborne pathogen that causes enterogastritis among humans, livestock and poultry, and it not only causes huge economic losses for the feed industry but also endangers public health around the world. However, the prevention and treatment of Salmonella infection has remained poorly developed because of its antibiotic resistance. Bacterial quorum sensing (QS) system is an intercellular cell-cell communication mechanism involving multiple cellular processes, especially bacterial virulence, such as biofilm formation, motility, adherence, and invasion. Therefore, blocking the QS system may be a new strategy for Salmonella infection independent of antibiotic treatment. Here, we have reviewed the central role of the QS system in virulence regulation of Salmonella and summarized the most recent advances about quorum quenching (QQ) in virulence attenuation during Salmonella infection. Unraveling the complex relationship between QS and bacterial virulence may provide new insight into the therapy of pathogen infection.

Left atrial strain for predicting recurrence in patients with non-valvular atrial fibrillation after catheter ablation: a single-center two-dimensional speckle tracking retrospective study.

BACKGROUND: Although catheter ablation (CA) is an effective treatment for non-valvular atrial fibrillation (AF), a good many of patients still have a recurrence following post-operation. Prediction of AF recurrence by evaluating left atrial (LA) phase function with speckle tracking echocardiography (STE) may be helpful for risk stratification and clinical management for AF patients. Therefore, the current study aimed to assess the prognostic value of LA strains in non-valvular AF patients after CA. METHODS: A total of 95 non-valvular AF patients (70.5% paroxysmal AF, 56.8% males, mean age 63.2 ± 9.7 years) were included in this retrospective study between October 2019 and August 2020. Transthoracic echocardiography was performed in all the subjects and STE was used to analyze the LA reservoir strain (LASr), LA conduit strain (LAScd) and LA contractile strain (LASct) during different phases before CA. Patients were followed up with until January 2022. The endpoint was AF recurrence. RESULTS: Over a median follow-up period of 26.0 months (interquartile range, 24.7-26.7 months), 26 patients experienced recurrence and 69 stayed in sinus rhythm. Compared with no-recurrence group, maximum volume of LA (LAVmax), minimum volume of LA (LAVmin) and LA volume index (LAVI) were increased in the recurrence group, while LAEF, LASr and LASct were worsened (P < 0.05). Multivariable logistic regression analysis revealed that LASct was an independent predictor of AF recurrence (odds ratio, 0.89; 95% confidence interval (CI), 0.82-0.97; P = 0.007) and receiver operating characteristic (ROC) curve analysis showed an area under the curve of LASct<8% was 0.70 (95% CI, 0.59-0.79; P = 0.0008). CONCLUSIONS: LASct was of independent predictive value of AF recurrence. LA function assessed by STE may contribute to the risk stratification for AF patients and selection of suitable patients for CA.

Sequential multidisciplinary minimally invasive therapeutic strategy for heart failure caused by four diseases: A case report.

BACKGROUND: The coexistence with patent ductus arteriosus (PDA), mitral valve prolapse (MVP), atrial fibrillation (AF) and hyperthyroidism is extremely rare and complex. The optimal therapeutic strategy is difficult to develop. CASE SUMMARY: A 27-year-old female with PDA, MVP, AF and hyperthyroidism presented with severe dyspnea. Given that a one-stage operation for PDA, MVP and AF is high risk, we preferred a sequential multidisciplinary minimally invasive therapeutic strategy. First, PDA transcatheter closure was performed. Hyperthyroidism and heart failure were simultaneously controlled via medical treatment. Video-assisted thoracoscopic mitral valve repair and left atrial appendage occlusion were performed when heart failure was controlled. Under this therapeutic strategy, the patient's sinus rhythm was restored and maintained. Two years after the treatment, the symptoms of heart failure were relieved, and the enlarged heart was reversed. CONCLUSION: Sequential multidisciplinary therapeutic strategies, which take advantage of both internal medicine and surgical approaches, might be reasonable for this type of disease.