Propranolol can correct prolonged QT intervals in patients with cirrhosis.

Background: Prolonged QT intervals are extremely common in patients with cirrhosis and affect their treatment outcomes. Propranolol is often used to prevent gastroesophageal variceal hemorrhage in patients with cirrhosis; however, it is uncertain whether propranolol exerts a corrective effect on QT interval prolongation in patients with cirrhosis. Aim: The study aimed to investigate the therapeutic effects of propranolol on patients with cirrhosis and prolonged QT intervals. Methods: A retrospective cohort study approach was adopted. Patients with cirrhosis complicated by moderate-to-severe gastroesophageal varices, who were hospitalized at the Affiliated Hospital of Guangdong Medical University between 1 December 2020 and 31 November 2022, were included in the study. The patients were divided into the propranolol and control groups based on whether they had received propranolol. Upon admission, the patients underwent tests on liver and kidney functions, electrolytes, and coagulation function, as well as abdominal ultrasonography and electrocardiography. In addition to conventional treatment, the patients were followed up after the use or non-use of propranolol for treatment and subsequently underwent reexamination of the aforementioned tests. Results: The propranolol group (26 patients) had an average baseline corrected QT (QTc) interval of 450.23 ± 37.18 ms, of which 14 patients (53.8%) exhibited QTc interval prolongation. Follow-up was continued for a median duration of 7.00 days after the administration of propranolol and conventional treatment. Electrocardiographic reexamination revealed a decrease in the QTc interval to 431.04 ± 34.64 ms (p = 0.014), and the number of patients with QTc interval prolongation decreased to five (19.2%; p < 0.001). After treatment with propranolol and multimodal therapy, QTc interval normalization occurred in nine patients with QTc interval prolongation, leading to a normalization rate of 64.3% (9/14). The control group (n = 58) had an average baseline QTc interval of 453.74 ± 30.03 ms, of which 33 patients (56.9%) exhibited QTc interval prolongation. After follow-up for a median duration of 7.50 days, the QTc interval was 451.79 ± 34.56 ms (p = 0.482), and the number of patients with QTc interval prolongation decreased to 30 (51.7%; p = 0.457). The QTc interval normalization rate of patients in the control group with QTc interval prolongation was merely 10.0% (3/33), which was significantly lower than that in the propranolol group (p < 0.001). Conclusion: In patients with cirrhosis complicated by QT interval prolongation, the short-term use of propranolol aids in correction of a long QT interval and provides positive therapeutic value for cirrhotic cardiomyopathy.

Timing of general anesthesia for pediatric patients recovering from COVID-19: a prospective cohort study.

OBJECTIVE: To explore the timing of general anesthesia for pediatric patients who have recovered from novel coronavirus infection and summarize anesthesia-related complications. METHODS: We summarized the perioperative management of children under 14 years of age who underwent general anesthesia in our hospital according to national epidemic prevention and control requirements. We compared the incidence of postoperative pulmonary complications within 2 weeks (Group A), 3-4 weeks (Group B), and 5-6 weeks (Group C) after COVID-19 recovery. RESULTS: There were differences among the three groups in terms of decreased blood oxygen saturation (< 94%), secretions, and coughing during the PACU period. The risk of low blood oxygen saturation during PACU decreased as the time of COVID-19 recovery extended in the three groups. Compared to Group A, the risk of low blood oxygen saturation was lower in Group B. The presence of respiratory symptoms and a body temperature above 40℃ increased the risk of decreased blood oxygen saturation. The proportion of children aged 11-14 years and children with high fever experiencing decreased blood oxygen saturation during PACU was higher in Groups A and B. Among the three groups, children with respiratory symptoms and longer illness duration had a higher proportion of decreased blood oxygen saturation during PACU. CONCLUSION: Pediatric patients who have recovered from COVID-19 for more than 2 weeks have a lower risk of postoperative complications after general anesthesia. For children with respiratory system symptoms or high fever, there is a higher risk of transient blood oxygen saturation decrease during PACU. For older children, those with high fever, respiratory system symptoms, or longer illness duration, it is recommended to appropriately extend the time from COVID-19 recovery to surgery.

Correlation between membrane proteins and sizes of extracellular vesicles and particles: A potential signature for cancer diagnosis.

Extracellular vesicles and particles (EVPs) are recognized as ideal liquid biopsy tools for cancer detection, and membrane proteins are commonly used EVP biomarkers. However, bulk analysis of EVP membrane protein biomarkers typically fails to meet the clinical requirement for diagnostic accuracy. We investigated the correlation between the membrane protein expression level, the binding kinetics to aptamers and the sizes of EVPs with interferometric plasmonic microscopy (iPM), and demonstrated the implementation of the correlative signature to determine cancer types. Using EVPs collected from both cell model and clinical plasma samples with liver, lung, breast, or prostate cancer, we found that the selective set of membrane protein expression levels of five protein markers and their binding kinetics were highly heterogeneous across various sizes of EVPs, resulting in the low overall accuracy (<50%) in cancer classification with bulk analysis of all populations. By grouping the EVPs into three subpopulations according to their sizes, the overall accuracy could be increased to about 70%. We further grouped the EVPs into subpopulations with a 10 nm interval in sizes and analysed the correlation between the membrane proteins and sizes with a machine learning algorithm. The results show that the overall accuracy to discriminate cancer types could be improved to 85%. Therefore, this work highlights the significance of size-dependent subtyping of EVPs and suggests that the correlation between the selective set of membrane proteins and sizes of EVP can serve as a signature for clinical cancer diagnosis.

An improved VSG control strategy based on transient electromagnetic power compensation.

Virtual synchronous generator (VSG) not only increases the inertia of grid-connected system, but also brings the problem of active power oscillation under grid disturbance. Therefore, VSG control strategy and system model order reduction method with transient electromagnetic power compensation are proposed. The closed-loop active power small signal model of the system is established, and the influence of transient electromagnetic power compensation on the power stability of VSG is analyzed based on root locus method. By removing the items which have little influence on the stability of the system in the small signal model, the order is reduced to obtain the equivalent second-order model of the system. According to the second-order model, the quantitative design criteria of the system parameters are given. The proposed transient electromagnetic power compensation strategy not only increases the transient equivalent damping of the system, but also does not affect the primary frequency modulation characteristics and will not cause large overshoot of the output active power. The experimental results are consistent with the theoretical analysis, which testify the effectiveness and correctness of the system control strategy and the model reduction method.

A novel telomere-related gene prognostic signature for survival and drug treatment efficiency prediction in lung adenocarcinoma.

OBJECTIVE: Telomere-related genes (TRGs) play a critical role in various types of tumors. However, there is a lack of comprehensive exploration of their relevance in lung cancer. This research aimed to verify the relationship between TRGs gene expression and the prognosis of patients with lung adenocarcinoma (LUAD), as well as the prediction of drug treatment efficiency. METHODS: A total of 2093 TRGs were acquired from TelNet. The clinical information including age, tumor stage, follow up and outcome (death/survival) and TRGs expression profile of LUAD were obtained from the patients in The Cancer Genome Atlas (TCGA) database and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. The two databases were used to construct and verify a prognostic model based on the expression of hubTRGs. The tumor mutation burden, immune infiltration and subtypes, as well as IC50 prediction of multiple targeted drugs were also evaluated in TRGs-divided risk groups. RESULTS: A total of 335 TRGs were significantly differentially expressed in LUAD as compared with normal control. Among them, 9 TRGs (ABCC2, ABCC8, ALDH2, FOXP3, GNMT, JSRP1, MACF1, PLCD3, SULT4A1) were finally identified as hubGenes and used to construct a TRG risk score. The TRG risk score showed favorable performance in constructing a prognostic nomogram in predicting survival of LUAD, and the ROC curves at 1, 3 and 5 years were plotted and the AUROC values were 0.743, 0.754 and 0.735, respectively. Higher TRGs risk score correlated with worse immune subtypes and higher tumor mutation burden in LUAD tissues. In addition, the patients in TRG high risk group harbored a lower TIDE score which indicated potentially better response to immunotherapy. CONCLUSION: This study proposed a broad molecular signature of telomere-related genes that can be used in further functional and therapeutic investigations, and also represents an integrated modality for characterizing critical molecules when exploring novel targets for lung cancer immunotherapy.

Transient power equalization control strategy of virtual synchronous generator in isolated island microgrid with heterogeneous power supply.

In the parallel supply system of synchronous generator and virtual synchronous generator, the physical structure and control structure of the two kinds of power supply are quite different, and it is difficult to distribute the transient power of the two kinds of power supply evenly when the load changes abruptly. Especially in the case of sudden load increase, virtual synchronous generator bears too much load in the transient process because of its fast adjustment speed, and even causes short-term overload, which makes the capacity of virtual synchronous generator can not be fully utilized. In view of this problem, firstly, the mechanism of transient power uneven distribution of two heterogeneous power sources is explained from the differences of frequency modulation, voltage regulation and output impedance. Secondly, virtual speed regulation, virtual excitation and dynamic virtual impedance are added to the traditional virtual synchronous generator control to simulate the speed regulation characteristics and electromagnetic transient characteristics of the synchronous generator, so as to realize the transient and steady-state power equalization between heterogeneous power supplies when the virtual synchronous generator and the synchronous generator run in parallel. Thirdly, in order to ensure the fast dynamic response characteristics of the virtual synchronous generator in independent operation mode, the traditional virtual synchronous generator control algorithm is still maintained in independent operation mode, and the mode switching control link based on state tracking is designed to realize smooth switching between the two working modes. Finally, the hardware in loop experiment results based on RT-LAB show that the proposed control method can realize the transient and steady-state power equalization when the virtual synchronous generator and the synchronous generator operate in parallel, it can keep the fast voltage regulation and frequency modulation ability when the virtual synchronous generator operates independently, and can realize smooth switching between independent and parallel operation modes.

Population structure and genome-wide evolutionary signatures reveal putative climate-driven habitat change and local adaptation in the large yellow croaker.

The large yellow croaker (Larimichthys crocea) is one of the most economically valuable marine fish in China and is a notable species in ecological studies owing to a serious collapse of wild germplasm in the past few decades. The stock division and species distribution, which have important implications for ecological protection, germplasm recovery, and fishery resource management, have been debated since the 1960s. However, it is still uncertain even how many stocks exist in this species. To address this, we evaluated the fine-scale genetic structure of large yellow croaker populations distributed along the eastern and southern Chinese coastline based on 7.64 million SNP markers. Compared with the widely accepted stock boundaries proposed in the 1960s, our results revealed that a climate-driven habitat change probably occurred between the Naozhou (Nanhai) Stock and the Ming-Yuedong (Mindong) Stock. The boundary between these two stocks might have shifted northwards from the Pearl River Estuary to the northern area of the Taiwan Strait, accompanied by highly asymmetric introgression. In addition, we found divergent landscapes of natural selection between the stocks inhabiting northern and southern areas. The northern population exhibited highly agminated signatures of strong natural selection in genes related to developmental processes, whereas moderate and interspersed selective signatures were detected in many immune-related genes in the southern populations. These findings establish the stock status and genome-wide evolutionary landscapes of large yellow croaker, providing a basis for conservation, fisheries management and further evolutionary biology studies. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-023-00165-2.

Lensless holographic microscope with a time and memory-saving algorithm for large-volume imaging of organoids.

Organoids, the 3D culture systems derived from stem cells, are promising models for human organs. However, organoid study requires large-volume imaging with single cell resolution, which is beyond the spatial bandwidth limit of conventional optical microscopy. Herein, we propose a lensless holographic microscope empowered with a time and memory-saving algorithm. It solves the trade-off between the imaging field of view, resolution, and processing speed, and provides a practical tool for the study of organoids. We first build a compact microscopy system using a multi-angle LED illumination scheme and an on-chip structure. Then we develop a fast angular spectrum formula for fast reconstruction of oblique-illuminated coaxial holography under the under-sampling condition. Additionally, we derive a multi-angle illuminated filtered backpropagation algorithm to achieve high-precision and slice-wise recovery of 3D structures of objects. The reconstruction process demands only 1/50 of the memory required by a traditional optical diffraction tomography algorithm. Experimental results indicate that the proposed method can achieve 6.28 mm × 4.71 mm × 0.37 mm volume imaging within 104 s. Through the standardized polystyrene beads test, we demonstrate that the proposed microscope has micrometer-scale resolution in both lateral and axial directions. In addition, the 3D imaging results of salivary gland organoids show great application prospects of the proposed method in the field of living biological sampling imaging.

EARLY INITIATION OF RENAL REPLACEMENT THERAPY IN INTENSIVE CARE UNIT PATIENTS WITH BOTH ACUTE RESPIRATORY DISTRESS SYNDROME AND SEPSIS WITH OR WITHOUT RENAL FAILURE: A RETROSPECTIVE COHORT STUDY BASED ON PROPENSITY SCORE MATCHING.

ABSTRACT: Background: It is unknown whether early renal replacement therapy (RRT) initiation strategy in intensive care unit (ICU) patients with both acute respiratory distress syndrome (ARDS) and sepsis with or without renal failure is clinically beneficial. Patients and methods: A total of 818 patients with both ARDS and sepsis admitted to the ICU of Tianjin Medical University General Hospital were included in the analysis. Early RRT was defined as initiating the RRT strategy within 24 h of admission. The relationship between early RRT and clinical outcomes, including primary (30-day mortality) and secondary (90-day mortality, serum creatinine, Pa o2 /Fi o2 , duration of invasive mechanical ventilation, cumulative fluid output, and cumulative fluid balance) outcomes, was compared using propensity score matching (PSM). Results: A total of 277 patients (33.9% of the total population) underwent an early RRT initiation strategy before PSM. After PSM, a cohort of 147 patients with early RRT and 147 patients without early RRT with matched baseline characteristics (including serum creatinine at admission) were constructed. Early RRT was not significantly associated with 30- (hazard ratio [HR], 1.25; 95% confidence interval [CI], 0.85-1.85; P = 0.258) or 90-day mortality (HR, 1.30; 95% CI, 0.91-1.87, P = 0.150). At each time point within 72 h after admission, there was no significant difference in serum creatinine, Pa o2 /Fi o2 and duration of mechanical ventilation between the early and the no early RRT groups. Early RRT significantly increased total output at all time points within 72 h of admission and reached a statistically significant negative fluid balance at 48 h. Conclusions: Early RRT initiation strategies had no statistically significant survival benefit in ICU patients with both ARDS and sepsis, with or without renal failure, nor did they significantly improve serum creatinine and oxygenation or shorten the duration of mechanical ventilation. The use and timing of RRT in such patients should be thoroughly investigated.

Decreased Expression of a Novel lncRNA FAM181A-AS1 is Associated with Poor Prognosis and Immune Infiltration in Lung Adenocarcinoma.

Background: There is no clear information regarding the role of FAM181A antisense RNA 1 (FAM181A-AS1) in lung adenocarcinoma (LUAD). We explored the relationship between FAM181A-AS1 and LUAD using bioinformatics analysis and experimental validation in this study. Methods: Statistics and databases were used to evaluate the relationship between clinical features in LUAD patients and FAM181A-AS1 expression, prognostic factors, regulation network, and immune infiltration of FAM181A-AS1 in function. LUAD cell lines were tested for FAM181A-AS1 expression using qRT-PCR. Results: FAM181A-AS1 showed significantly low expression in LUAD patients. Low FAM181A-AS1 expression predicted a poorer overall survival (OS) (HR: 0.66; 95% CI: 0.49-0.88; P=0.005) and disease specific survival (DSS) (HR: 0.64; 95% CI: 0.44-0.92; P=0.017) of LUAD patients. There was also an independent correlation between low FAM181A-AS1 expression (HR: 0.547; 95% CI: 0.350-0.857; P=0.008) and OS in LUAD patients. The FAM181A-AS1 high-expression phenotype was differentially enriched for M phase, cellular senescence, cell cycle checkpoints, chromatin modifying enzymes, ESR-mediated signaling, DNA repair, G2/M checkpoints, HCMV infection, and DNA double-strand break repair. A correlation was found between the expression of FAM181A-AS1 and immune infiltrating cells. A significant decrease in FAM181A-AS1 expression was observed in LUAD cell lines compared to Beas-2B. Conclusion: There was a significant association between low FAM181A-AS1 expression in LUAD patients and poor survival and immune infiltration. The FAM181A-AS1 gene may provide a useful biomarker for LUAD prognosis and immunotherapy response.

Risk stratification of patients with acute respiratory distress syndrome complicated with sepsis using lactate trajectories.

BACKGROUND: No consensus has been reached on an optimal blood lactate evaluation system although several approaches have been reported in the literature in recent years. A group-based trajectory modeling (GBTM) method could better stratify patients with acute respiratory distress syndrome (ARDS) complicated with sepsis in the intensive care unit (ICU). PATIENTS AND METHODS: 760 patients from the comprehensive ICU of Tianjin Medical University General Hospital with ARDS complicated with sepsis were eligible for analysis. Serial serum lactate levels were measured within 48 h of admission. In addition to the GBTM lactate groups, the initial lactate, peak lactate level, the area under the curve of serial lactate (lactate AUC), and lactate clearance were also considered for comparison. The short- and long-term outcomes were the 30- and 90-day mortality, respectively. RESULTS: Three lactate groups were identified based on GBTM, with group 3 exhibiting the worse short- [hazard ratio (HR) for 30-day mortality: 2.96, 95% confidence interval (CI) 1.79-4.87, P < 0.001] and long term (HR for 90-day mortality: 3.49, 95% CI 2.06-5.89, P < 0.001) outcomes followed by group 2 (HR for 30-day mortality: 2.05, 95% CI 1.48-2.84, P < 0.001 and HR for 90-day mortality: 1.99, 95% CI 1.48-2.67, P < 0.001). GBTM lactate groups exhibited significantly improved diagnostic performance of initial lactate + SOFA scores/APACHE II scores models. Based on the multivariable fractional polynomial interaction (MFPI) approach, GBTM lactate groups could better differentiate high-risk patients than the initial lactate groups in short- and long-term outcomes. CONCLUSIONS: To the best of our knowledge, this is the first report that GBTM-based serial blood lactate evaluations significantly improve the diagnostic capacity of traditional critical care evaluation systems and bring many advantages over previously documented lactate evaluation systems.

First genomic prediction and genome-wide association for complex growth-related traits in Rock Bream (Oplegnathus fasciatus).

Rock Bream (Oplegnathus fasciatus) is an important aquaculture species for offshore cage aquaculture and fish stocking of marine ranching in East Asia. Genomic selection has the potential to expedite genetic gain for the key target traits of a breeding program, but has not yet been evaluated in Oplegnathus. The purposes of the present study were to explore the performance of genomic selection to improve breeding value accuracy through real data analyses using six statistical models and to carry out genome-wide association studies (GWAS) to dissect the genetic architecture of economically vital growth-related traits (body weight, total length, and body depth) in the O. fasciatus population. After quality control, genotypes for 16,162 SNPs were acquired for 455 fish. Heritability was estimated to be moderate for the three traits (0.38 for BW, 0.33 for TL, and 0.24 for BD), and results of GWAS indicated that the underlying genetic architecture was polygenic. Six statistic models (GBLUP, BayesA, BayesB, BayesC, Bayesian Ridge-Regression, and Bayesian LASSO) showed similar performance for the predictability of genomic estimated breeding value (GEBV). The low SNP density (around 1 K selected SNP based on GWAS) is sufficient for accurate prediction on the breeding value for the three growth-related traits in the current studied population, which will provide a good compromise between genotyping costs and predictability in such standard breeding populations advanced. These consequences illustrate that the employment of genomic selection in O. fasciatus breeding could provide advantages for the selection of breeding candidates to facilitate complex economic growth traits.

Evaluating dynamic effects of dietary glycerol monolaurate on the productive performance and flesh quality of large yellow croaker (Larimichthys crocea).

The effects of GML (Glycerol monolaurate) supplementation with two level (0.5 and 1.0 g kg-1) on the productive performance and flesh quality of large yellow croaker (360 per group) were investigated during feeding (23,50-days) and fasting stage (23,70-days). The GML supplementation significantly increased body weight after 23-days and crude protein, inosinic acid, and yellowness after 50-days. Moreover, it increased hardness, springiness, and chewiness by increasing the collagen content, myofiber density, and decreasing myofiber diameter. The high GML supplementation increased the total free amino acids, delicate amino acids, monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (n-3 PUFA), and EPA + DHA, whereas it decreased the content of saturated fatty acids/unsaturated fatty acids (SFA/UFA). During fasting, better body shape and color were shown were shown at high GML supplementation. Conclusively, high dose GML supplementation exerted promising effects on the productive performance and flesh quality of large yellow croaker.

Comparative transcriptome analysis reveals immunoregulation mechanism of lncRNA-mRNA in gill and skin of large yellow croaker (Larimichthys crocea) in response to Cryptocaryon irritans infection.

BACKGROUND: Cryptocaryonosis caused by Cryptocaryon irritans is one of the major diseases of large yellow croaker (Larimichthys crocea), which lead to massive economic losses annually to the aquaculture industry of L. crocea. Although there have been some studies on the pathogenesis for cryptocaryonosis, little is known about the innate defense mechanism of different immune organs of large yellow croaker. RESULTS: In order to analyze the roles of long non-coding RNAs and genes specifically expressed between immune organs during the infection of C. irritans, in this study, by comparing transcriptome data from different tissues of L. crocea, we identified tissue-specific transcripts in the gills and skin, including 507 DE lncRNAs and 1592 DEGs identified in the gills, and 110 DE lncRNAs and 1160 DEGs identified in the skin. Furthermore, we constructed transcriptome co-expression profiles of L. crocea gill and skin, including 7,503 long noncoding RNAs (lncRNAs) and 23,172 protein-coding genes. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that the DEGs and the target genes of the DE lncRNAs in the gill were specifically enriched in several pathways related to immune such as HIF-1 signaling pathway. The target genes of DE lncRNAs and DEGs in the skin are specifically enriched in the complement and coagulation cascade pathways. Protein-protein interaction (PPI) network analysis identified 3 hub genes including NFKBIA, TNFAIP3 and CEBPB, and 5 important DE lncRNAs including MSTRG.24134.4, MSTRG.3038.5, MSTRG.27019.3, MSTRG.26559.1, and MSTRG.10983.1. The expression patterns of 6 randomly selected differentially expressed immune-related genes were validated using the quantitative real-time PCR method. CONCLUSIONS: In short, our study is helpful to explore the potential interplay between lncRNAs and protein coding genes in different tissues of L. crocea post C. irritans and the molecular mechanism of pathogenesis for cryptocaryonosis. HIGHLIGHTS: Skin and gills are important sources of pro-inflammatory molecules, and their gene expression patterns are tissue-specific after C. irritans infection. 15 DEGs and 5 DE lncRNAs were identified as hub regulatory elements after C. irritans infection The HIF-1 signaling pathway and the complement and coagulation cascade pathway may be key tissue-specific regulatory pathways in gills and skin, respectively.

Integrated metabolomic and gene expression analyses to study the effects of glycerol monolaurate on flesh quality in large yellow croaker (Larimichthys crocea).

To improve the quality of cultured large yellow croaker (Larimichthys crocea), this study was performed to study the impacts of glycerol monolaurate (GML) on the nutritional value, growth performance, muscle texture, and taste intensity of L. crocea. The results showed that GML as a feed additive significantly increased the crude lipid content and reduced the diameters of muscle fibers, which in turn markedly altered the flesh texture in terms of cohesiveness. Moreover, the taste indicators (umami and richness) and flavor-related amino acid (glutamic acid, glycine, and proline) contents of L. crocea muscle were significantly higher in the GML group. Metabolomic and gene expression analyses showed that GML supplementation could significantly improve amino acid biosynthesis and metabolism, promote protein and lipid synthesis, and activate myogenic-related signaling pathways of L. crocea. Consequently, adding an appropriate amount of GML to fish feed would be conducive to providing healthy, nutrient-rich and acceptably flavored aquatic-products.

Molecular Hydrogen: A Promising Adjunctive Strategy for the Treatment of the COVID-19.

Coronavirus disease 2019 (COVID-19) is an acute respiratory disease caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has no specific and effective treatment. The pathophysiological process of the COVID-19 is an excessive inflammatory response after an organism infects with a virus. Inflammatory storms play an important role in the development of the COVID-19. A large number of studies have confirmed that hydrogen has a therapeutic effect on many diseases via inhibiting excessive inflammatory cells and factors. Recently, a study led by the Academician Zhong Nanshan in China on the treatment of the patients with the COVID-19 by inhalation of a mixed gas composed of hydrogen and oxygen has attracted widespread international attention and hydrogen therapy has also been included in a new treatment plan for the COVID-19 in China. This study mainly describes the mechanism of occurrence of the COVID-19, summarizes the therapeutic effects and underlying mechanisms of hydrogen on the critical disease, and analyzes the feasibility and potential therapeutic targets of hydrogen for the treatment of the COVID-19.

The contributions of fliG gene to the pathogenicity of Pseudomonas plecoglossicida and pathogen-host interactions with Epinephelus coioides.

Pseudomonas plecoglossicida is a Gram-negative aerobic rod-shaped bacterium with polar flagella. It is the causative agent of visceral white spot disease in cultured fish, resulting in serious economic losses. In our previous study, RNA sequencing showed that the expression of the fliG gene in P. plecoglossicida is significantly up-regulated during infection of orange-spotted grouper (Epinephelus coioides). In this study, four P. plecoglossicida RNA interference (RNAi) mutants were successfully constructed by linking four short hairpin RNAs (shRNAs), which target different sites of the fliG gene, to pCM130/tac, respectively. The mRNA expression levels of the fliG gene in P. plecoglossicida were significantly decreased in four mutants. The shRNA-335 mutant (fliG-RNAi strain) showed the best silencing efficiency (88.2%) and was thus chosen for further analysis. Electron microscopy indicated that the flagella of the fliG-RNAi strain of P. plecoglossicida were shorter and finer than those of the wild type strain. The fliG-RNAi strain also showed significantly decreased mobility, chemotaxis, adhesion, and biofilm formation. Furthermore, compared with wild type strain infection, E. coioides infected with the fliG-RNAi strain exhibited a 0.5-d delay in the time of first death and 55% reduction in accumulated mortality, as well as milder splenic symptoms. RNAi of the fliG gene significantly affected the transcriptomes of both pathogen and host in the infected spleens of E. coioides. KEGG analysis revealed that the flagellar assembly pathway, bacterial chemotaxis pathway, and starch and sucrose metabolism pathway were significantly enriched in the pathogen at 3 days post infection (dpi). In contrast, the complement and coagulation cascade pathway and antigen processing and presentation pathway were significantly enriched in the host at 3 dpi. More immune-related pathways were enriched at 5 dpi and more differentially expressed genes were found in the complement and coagulation cascade and antigen processing and presentation pathways. Cytokine-cytokine receptor interaction, hematopoietic cell lineage, and IgA-producing intestinal immune network pathways were significantly enriched in the host at 5 dpi. These results indicate that fliG is an important virulence gene of P. plecoglossicida and contributes to the pathogenicity of P. plecoglossicida as well as pathogen-host interactions with E. coioides.