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Myocardial ischemia/reperfusion injury (MIRI) is related to ferroptosis and apoptosis elicited by reactive oxygen species (ROS). In this research, we investigated the protective effect of salvianolic acid B (SAB) as a natural antioxidant on ferroptosis and apoptosis in the MIRI process, and discussed the protective mechanism inhibiting ubiquitin-proteasome degradation of glutathione peroxidase 4 (GPX4) and the c-Jun N-terminal kinases (JNK) apoptosis signal pathway. We observed that ferroptosis and apoptosis occurred in the MIRI rat model in vivo and the H9c2 cardiomyocyte hypoxia/reoxygenation (H/R) damage model in vitro. SAB can alleviate tissue damage related to ROS, ferroptosis and apoptosis. Ubiquitin-proteasome degradation of GPX4 occurred in H/R models, and SAB reduced the ubiquitin-proteasome degradation of GPX4. SAB downregulates JNK phosphorylation and the expression of BCL2-Associated X (Bax)/B-cell lymphoma-2 (Bcl-2) and Caspase-3 to inhibit apoptosis. The role of GPX4 in the cardioprotection of SAB was further verified by the elimination effect of the GPX4 inhibitor RAS-selective lethal 3 (RSL3). This research shows that SAB may be used as a myocardial protective agent against oxidative stress, ferroptosis and apoptosis, and has potential clinical application prospects. [ABSTRACT FROM AUTHOR]

• Rhizoma coptidis has a good inhibitory effect on Vibrio alginolyticus. • Transcriptomic analysis reveals the molecular mechanism of virulence genes. • Rhizoma coptidis could potnetially be a substitute for antibiotics. Rhizoma coptidis , a Chinese herbal medicine widely used to treat various bacterial infections, has the potential to develop antibiotic substitutes to overcome the drug resistance of Vibrio alginolyticus. To study the inhibitory effect of R. coptidis on V. alginolyticus , we sequenced the transcriptomes of three groups of samples of wild-type V. alginolyticus (CK) and V. alginolyticus , which were stressed by 5 mg/mL R. coptidis for 2 h (RC_2 h) and 4 h (RC_4 h). CK was compared with RC_2 h and RC_4 h, respectively, and a total of 1565 differentially expressed genes (DEGs) (988 up-regulated and 577 down-regulated) and 1737 DEGs (1152 up-regulated and 585 down-regulated) were identified. Comparing RC_2 h with RC_4 h, 156 DEGs (114 up-regulated and 42 down-regulated) were identified. The ability of biofilm formation and motility of V. alginolyticus altered upon with different concentrations of R. coptidis. Interestingly, relative expression patterns of virulence genes appeared statistically significantly varied, upon different concentrations of R. coptidis extract. DEGs were annotated to the Gene Ontology (GO) database for function enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, the results showed that the main enriched pathways, was those related to the virulence of V. alginolyticus. This study provides a new perspective for understanding the complex pathogenic mechanism of V. alginolyticus. R. coptidis could potnetially be used as alternative or complimnetary to antibiotics to treat infections after further research. [ABSTRACT FROM AUTHOR]

Interaction between bacterial pathogen and aquatic animal host is exceedingly complex, which involves large dynamic changes in gene expression during different stages of the disease. However, research on identifying key virulence genes based on the dynamics of gene expression changes of a one‐sided bacterial pathogen in tissue has not been reported so far across different stages of infectious disease. The clpV for the T6SS of Pseudomonas plecoglossicida was identified for a candidate for key virulence gene based on dynamic changes of gene expression. For the Epinephelus coioides infected using clpV‐RNAi strain, no deaths were observed up to 20 dpi. The spleens, kidneys and livers of all the E. coioides that received clpV‐RNAi strain failed to develop visible nodules at 5–8 dpi, with the swelling gradually disappearing. The burdens of clpV‐RNAi strain in the spleen and blood were greatly reduced at most of the time points after injection, and the burdens of clpV‐RNAi strain in the head kidneys and trunk kidneys also had a sharp reduction from 72 to 120 hpi. This paper provides a new insight into the discovery of key virulence genes of pathogens in infected tissue systems. [ABSTRACT FROM AUTHOR]

• 1200 μg/mL F. schisandrae inhibited the growth of V.alginolyticus ND-01. • V. alginolyticus under high concentrations of F. schisandrae stress had insufficient ability in the whole biofilm formation process. • DEGs was involved in the following functional categories: metabolic process, single-organism process, catalytic activity and localization. Due to the abusive use of antibiotics, bacterial resistance has become a global problem and poses severe threats to aquaculture. The drug-resistant diseases caused by Vibrio alginolyticus have caused significant economic losses to cultured marine fish. Fructus schisandrae is used to treat inflammatory diseases in China and Japan. There have been no reports of bacterial molecular mechanisms associated with F. schisandrae stress. In this study, the inhibiting effect of F. schisandrae on the growth of V. alginolyticus was detected to understand response mechanisms at the molecular level. The antibacterial tests were analyzed via next-generation deep sequencing technology (RNA sequencing, RNA-seq). Wild V. alginolyticus (CK) was compared with V. alginolyticus, F. schisandrae incubated for 2 h, and V. alginolyticus, F. schisandrae incubated for 4 h. Our results revealed that there were 582 genes (236 upregulated and 346 downregulated) and 1068 genes (376 upregulated and 692 downregulated), respectively. Differentially expressed genes (DEGs) were involved in the following functional categories: metabolic process, single-organism process, catalytic activity, cellular process, binding, membrane, cell part, cell, and localization. FS_2 h was compared with FS_4 h, and 21 genes (14 upregulated and 7 downregulated) were obtained. The RNA-seq results were validated by detecting the expression levels of 13 genes using quantitative real-time polymerase chain reaction (qRT-PCR). The qRT-PCR results matched those of the sequencing, which reinforced the reliability of the RNA-seq. The results revealed the transcriptional response of V. alginolyticus to F. schisandrae , which will provide new ideas for studying V. alginolyticus' complex virulence molecular mechanism and the possibility of developing Schisandra to prevent and treat drug-resistant diseases. [ABSTRACT FROM AUTHOR]

• The rainfall erosivity increased in the karst region of SW China from 1901 to 2020. • There are significant differences in the spatial distribution of annual, seasonal and monthly rainfall erosivity. • The trend of increasing rainfall erosivity is more obvious in January in winter. • More variability is found in the monthly scale study. Global warming changes global and regional patterns of precipitation, which will inevitably lead to more severe soil erosion risks in fragile karst ecosystems. Understanding the variation pattern of rainfall erosivity is vital for preventing and controlling soil erosion in the karst region of southwestern (SW) China. In this study, the spatiotemporal dynamic evolution pattern of the rainfall erosivity throughout the year in the karst region of SW China was explored using regression analysis and the Mann–Kendall test based on the monthly rainfall data for 1901–2020 in the CRU_TS 4.05 dataset. The results indicate that: (1) The rainfall erosivity in the karst region of SW China varies with latitude and is more significant in the south, and its interannual variations are linear and positive. (2) The interannual linear increase in rainfall erosivity was the greatest in the peak forest-plain rocky desertification control zone (FLPY). (3) The rainfall erosivity exhibited an increasing trend in spring, summer, and winter, with the most significant increase in January. (4) More variability was observed on the monthly scale. In summary, future investigations and control of soil erosion in the karst region of SW China under climate change should focus on the critical times when (e.g., January) and areas where (e.g., peak forest-plain rocky desertification control zone) rainfall erosivity changes significantly. Identifying the shift in the rainfall erosivity patterns caused by climate change is critical for assessing soil erosion risks in karst areas and for formulating countermeasures. [ABSTRACT FROM AUTHOR]

Macrophage migration inhibitory factor (MIF) is a key pro-inflammatory cytokine in immuno-inflammatory diseases. For the first time, we examined the expression of MIF in Epinephelus awoara (E. awoara). MIF expressions have been detected in the head kidney, spleen, liver, brain, intestine, gill, heart, stomach, and muscle of E. awoara infected with Vibrio parahaemolyticus. The mRNA levels observed in infected groupers were higher than those in healthy groupers. MIF, tumor necrosis factor-α (TNF-α), and interleukin-1 (IL-1) tissue levels have been measured by ELISA. A significant increase in MIF, TNF-α, and IL-1 tissue levels have been found in the treatment groups compared with those in controls. MIF, TNF-α and IL-1 tissue levels in the spleen, head kidney, intestine, and liver of E. awoara during the challenge trial with V. parahaemolyticus were significantly higher than those in controls. There was evidence of functions of MIF in a positive feedback loop with TNF-α and IL-1 that could perpetuate the inflammatory process in grouper infected with V. parahaemolyticus. In conclusion, these results indicated that MIF was related to pathogen-induced immune response. [ABSTRACT FROM AUTHOR]

• A significant decrease in gene expression of adhesion-deficient V. harveyi. • fliA , fliR , and flrB were responsible for flagellation and silenced via RNAi. • fliA , fliR , and flrB have important roles in the adhesion of V. harveyi. • fliA , fliR , flrB regulate bacterial adhesion by affecting its motility, biofilm formation. • fliA , fliR , flrB regulate adhesion ability of V. harveyi in different environments. Bacteria adhesion to fish mucus is a crucial virulence mechanism. As the initial step of bacterial infection, adhesion is impacted by bacterial motility and environmental conditions. However, its molecular mechanism is yet unclear. In this study, a significant decrease in gene expression of adhesion-deficient Vibrio harveyi was observed when the bacteria were subjected by Cu2+(50 mg/L), Pb2+(100 mg/L), Hg2+(25 mg/L), and Zn2+(50 mg/L). The genes fliA , fliR , and flrB were responsible for flagellation; being crucial for adhesion, these genes were identified and silenced via RNAi. After silencing of these genes by RNAi technology, the ability of adhesion, biofilm formation, motility, and flagella synthesis of V. harveyi were considerably reduced. Compared with the control group, it was observed that the expression levels of fliS , fliD , flgH , and flrC were significant down-regulated in fliR -RNAi, flrB -RNAi, and fliA -RNAi. This data indicates that the expression levels of most virulence genes are affected by fliA , fliR , and flrB. Also, the expression of fliA , fliR , and flrB can be influenced by the salinity, temperature, and pH. The results show that: (1) fliA , fliR , and flrB have important roles in the adhesion of V. harveyi ; (2) fliA , fliR , and flrB can regulate bacterial adhesion by affecting its motility, and biofilm formation; (3) fliA , fliR , and flrB can regulate adhesion ability of V. harveyi in different environments. [ABSTRACT FROM AUTHOR]

This study was undertaken to address a lack of understanding of the early developmental stages of the tropical elasmobranch whitespotted bamboo shark,Chiloscyllium plagiosum, to assist with advancement of its aquaculture. It is the first report of the histological and ultrastructural characteristics of its developing digestive tract. The study was carried out from hatching to 60 days after hatching (DAH). Embryos for this study were maintained in the laboratory. Histological investigations yielded the following data. At hatching, the gut of an embryo consisted of an undifferentiated straight tube that lay over the yolk sac. The digestive tract was differentiated into buccopharynx, esophagus, stomach, and intestine by 8 DAH. During the preflexion phase (within 16 DAH), the mucous cells of the esophagus were differentiated. Gastric glands were present at 60 DAH, indicating the transition from the embryonic to the juvenile stage and the acquisition of an adult mode of digestion. The lumen of the intestine appeared on 6 DAH; the intestinal valve appeared and divided the intestine into anterior and posterior sections on 20 DAH. The liver and the pancreas were formed on 8 DAH. The yolk sac was partially depleted by 80 DAH. In terms of ultrastructure, on 30 DAH, the anterior section of the esophagus was lined by a stratified epithelium, whereas the posterior section was lined by simple tall columnar epithelial cells. Goblet cells and oxynticopeptic cells were found in the stomach. The pancreatic acinar cells were strongly elongated and of two types: one with a pale and the other with a more opaque cytoplasm. [ABSTRACT FROM AUTHOR]

The importance of autophagy in the generation of memory CD8+ T cells in vivo is not well defined. We report here that autophagy was dynamically regulated in virus-specific CD8+ T cells during acute infection of mice with lymphocytic choriomeningitis virus. In contrast to the current paradigm, autophagy decreased in activated proliferating effector CD8+ T cells and was then upregulated when the cells stopped dividing just before the contraction phase. Consistent with those findings, deletion of the gene encoding either of the autophagy-related molecules Atg5 or Atg7 had little to no effect on the proliferation and function of effector cells, but these autophagy-deficient effector cells had survival defects that resulted in compromised formation of memory T cells. Our studies define when autophagy is needed during effector and memory differentiation and warrant reexamination of the relationship between T cell activation and autophagy. [ABSTRACT FROM AUTHOR]

What does regressingYonXversus regressingXonYhave to do with Markov chain Monte Carlo (MCMC)? It turns out that many strategies for speeding up data augmentation (DA) type algorithms can be understood as fostering independence or “de-correlation” between a regression function and the corresponding residual, thereby reducing or even eliminating dependence among MCMC iterates. There are two general classes of algorithms, those corresponding to regressing parameters on augmented data/auxiliary variables and those that operate the other way around. The interweaving strategy of Yu and Meng provides a general recipe to automatically take advantage of both, and it is the existence of two different types of residuals that makes the interweaving strategy seemingly magical in some cases and promising in general. The concept of residuals—which depends on actual data—also highlights the potential for substantial improvements when DA schemes are allowed to depend on the observed data. At the same time, there is an intriguing phase transition type of phenomenon regarding choosing (partially) residual augmentation schemes, reminding us once more of the prevailing issue of trade-off between robustness and efficiency. This article reports on these latest theoretical investigations (using a class of normal/independence models) and empirical findings (using a posterior sampling for a probit regression) in the search for effective residual augmentations—and ultimately more MCMC algorithms—that meet the 3-S criterion:simple, stable, and speedy.Supplementary materials for the article are available online. [ABSTRACT FROM AUTHOR]

Abstract: mTOR is an evolutionarily conserved serine/threonine kinase that plays a critical role in cell growth and metabolism by sensing different environmental cues. There is a growing appreciation of mTOR in immunology for its role in integrating diverse signals from the immune microenvironment and coordinating the functions of immune cells and their metabolism. In CD8 T cells, mTOR has shown to influence cellular commitment to effector versus memory programming; in CD4 T cells, mTOR integrates environmental cues that instruct effector cell differentiation. In this review, we summarize and discuss recent advances in the field, with a focus on the mechanisms through which mTOR regulates cellular and humoral immunity. Further understanding will enable the manipulation of mTOR signaling to direct the biological functions of immune cells, which holds great potential for improving immune therapies and vaccination against infections and cancer. [Copyright &y& Elsevier]

Abstract: Simultaneous microarray-based transcription analysis of 4987 Anopheles stephensi midgut and Plasmodium berghei infection stage specific cDNAs was done at seven successive time points: 6, 20 and 40h, and 4, 8, 14 and 20 days after ingestion of malaria infected blood. The study reveals the molecular components of several Anopheles processes relating to blood digestion, midgut expansion and response to Plasmodium-infected blood such as digestive enzymes, transporters, cytoskeletal and structural components and stress and immune responsive factors. In parallel, the analysis provide detailed expression patterns of Plasmodium genes encoding essential developmental and metabolic factors and proteins implicated in interaction with the mosquito vector and vertebrate host such as kinases, transcription and translational factors, cytoskeletal components and a variety of surface proteins, some of which are potent vaccine targets. Temporal correlation between transcription profiles of both organisms identifies putative gene clusters of interacting processes, such as Plasmodium invasion of the midgut epithelium, Anopheles immune responses to Plasmodium infection, and apoptosis and expulsion of invaded midgut cells from the epithelium. Intriguing transcription patterns for highly variable Plasmodium surface antigens may indicate parasite strategies to avoid recognition by the mosquito''s immune surveillance system. [Copyright &y& Elsevier]

Background: Nutritional deficiencies (ND) continue to threaten the lives of millions of people around the world, with children being the worst hit. Nevertheless, no systematic study of the epidemiological features of child ND has been conducted so far. Therefore, we aimed to comprehensively assess the burden of pediatric ND. Methods: We analyzed data on pediatric ND between 1990 and 2019 from the Global Burden of Disease study (GBD) 2019 at the global, regional, and national levels. In addition, joinpoint regression models were used to assess temporal trends. Results: In 2019, the number of prevalent cases of childhood malnutrition increased to 435,071,628 globally. The global age-standardized incidence, prevalence, and DALY rates showed an increasing trend between 1990 and 2019. Meanwhile, the burden of child malnutrition was negatively correlated with sociodemographic index (SDI). Asia and Africa still carried the heaviest burden. The burden and trends of child malnutrition varied considerably across countries and regions. At the age level, we found that malnutrition was significantly more prevalent among children < 5 years of age. Conclusion: Pediatric ND remains a major public health challenge, especially in areas with low SDI. Therefore, primary healthcare services in developing countries should be improved, and effective measures, such as enhanced pre-school education, strengthened nutritional support, and early and aggressive treatment, need to be developed. [ABSTRACT FROM AUTHOR]

Aryl hydrocarbon receptor (AhR), a ligand-dependent transcriptional factor that responds to environmental chemicals, has been recently found to be closely associated with immune response in mammals. Pseudomonas plecoglossicida (P. plecoglossicida) is a temperature-dependent bacterial pathogen of visceral white spot disease in fish. Using dual RNA-seq, we previously evaluated the expression levels of ahr1a , ahr1b , ahr2 and cyp1a in the spleen of Epinephelus coioides at different time points after infection with P. plecoglossicida. In the present study, the expression levels of ahr1a , ahr1b , ahr2 and cyp1a in different organs of E. coioides and Danio rerio showed similar trends after being infected by P. plecoglossicida. It also was noted that liver, intestine, spleen, and heart were the most obviously affected organs, and ahr2 particularly showed a dramatically increase in the spleen. Subsequently, macrophages of E. coioides were isolated, and then infected by P. plecoglossicida , followed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay, which revealed that the expression level of ahr1a in macrophages was significantly down-regulated, while expression levels of ahr1b , ahr2 and cyp1a were noticeably up-regulated. Eventually, it was noted that ahr1b and ahr2 were knocked-down in macrophages, and intracellular survival rate and immune escape rate of P. plecoglossicida were markedly improved. Taken together, ahr1a , ahr1b , ahr2 and cyp1a participate in the immune response to P. plecoglossicida in different organs of fish, while ahr1b and ahr2 may play pivotal roles in the immune response of spleen and macrophages. • ahrs participated in the response to P. plecoglossicida in fish organs. • ahrs participated in the immune response in macrophages. • ahr1b and ahr2 affected the intracellular survival of P. plecoglossicida in macrophages. [ABSTRACT FROM AUTHOR]

The interactions between host and pathogen is exceedingly complex, which involves alterations at multiple molecular layers. However, research to simultaneously monitor the alterations of transcriptome and proteome between a bacterial pathogen and aquatic animal host through integrated dual RNA-seq and dual iTRAQ of tissue during infection is currently lacking. The important role of a diguanylate cyclase gene (L321_RS15240) in pathogenicity of Pseudomonas plecoglossicida against Epinephelus coioides was suggested by previous dual RNA-seq of our lab. Then L321_RS15240 -RNAi strains of P. plecoglossicida were constructed with pCM130/tac, and the mutant with the best silencing effect was selected for follow-up study. The RNAi of L321_RS15240 resulted in a significant decrease in bacterial virulence of P. plecoglossicida. The E. coioides spleens infected by wild type strain or L321_RS15240 -RNAi strain of P. plecoglossicida were subjected to dual RNA-seq and dual iTRAQ, respectively. The results showed that: RNAi of L321_RS15240 led to 1)alterations of host transcriptome associated with complement and coagulation cascades, ribosome, arginine and proline metabolism, and oxidative phosphorylation; 2)high expression of host proteins which related to phagosome and metabolism responses (metabolism of glutathione, amino sugar and nucleotide sugar); 3)the highly differentially expression of host lncRNAs and miRNAs. The differentially expressed proteins and mRNAs of pathogen were different after infection, but the functions of these proteins and mRNAs were mainly related to metabolism and virulence. This study provides a new insight to comprehensively understand the gene functions of pathogens and hosts at multiple molecular layers during in vivo infection. • RNAi significantly reduced the expression of L321_RS15240 gene of P. plecoglossicida. • RNAi of L321_RS15240 gene significantly reduced the virulence of P. plecoglossicida. • RNAi of L321_RS15240 gene altered the host immune response to P. plecoglossicida infection. [ABSTRACT FROM AUTHOR]

As an important pathogen in aquaculture, Pseudomonas plecoglossicida has caused heavy losses. The expression of an ABC transporter gene- L321_23611 of P. plecoglossicida at 18 °C was found significant higher than those at 28 °C by RNA-seq and qRT-PCR. RNAi significantly reduced the content of L321_ 23611 mRNA in P. plecoglossicida with a maximal decrease of 89.2%. Compared with the wild type strain, the infection of L321_23611- RNAi strain resulted in the reduction in mortality and the onset time delay of a kind of marine teleosts, Epinephelus coioides. The results of dual RNA-seq showed that the RNAi of L321_23611 resulted in a significant change in both pathogen and host transcriptome in the spleens of infected E. coioides. The result of GO and KEGG analysis from dual RNA-seq data showed both host genes of chemokine signaling pathway, coagulation and complement system, hematopoietic cell lineage pathway as well as hemoglobin complex GO term and pathogenic genes of bacterial-type flagellum-dependent cell mortality GO term and flagellar assembly, biosynthesis of amino acids and lysine biosynthesis systems pathways were mainly affected by L321_23611 gene of P. plecoglossicida. The results indicated that: 1. ABC transporter gene- L321_23611 was a virulent gene of P. plecoglossicida. 2. Both the activation of the host immune pathways and depression of pathogenic virulence-related pathways facilitated E. coioides to remove L321_23611 -RNAi strain than the wild type strain of P. plecoglossicida. • RNAi significantly reduced the content of L321_ 23611 mRNA of P. plecoglossicida. • RNAi of L321_23611 reduced the pathogenicity of P. plecoglossicida to E. coioides. • RNAi of L321_23611 significantly up-regulated host immune pathways. • RNAi of L321_23611 down-regulated some pathogenic genes of P. plecoglossicida. [ABSTRACT FROM AUTHOR]

Vibrio alginolyticus is a leading aquatic pathogen, causing huge losses to aquaculture. rpoS has been proven to play a variety of important roles in stress response and virulence in several bacteria. In our previous study, upon treatment with Cu2+, Pb2+, Hg2+ and low pH, the expression levels of rpoS were downregulated as assessed by RNA‐seq, while impaired adhesion ability was observed, indicating that rpoS might play roles in the regulation of adhesion. In the present study, the RNAi technology was used to knockdown rpoS in V. alginolyticus. In comparison with wild‐type V. alginolyticus, RNAi‐treated bacteria showed significantly impaired abilities of adhesion, growth, haemolytic, biofilm production, movement and virulence. Meanwhile, alterations of temperature, salinity, pH and starvation starkly affected rpoS expression. The present data suggested that rpoS is a critical regulator of virulence in V. alginolyticus; in addition, rpoS regulates bacterial adhesion in response to temperature, pH and nutrient content changes. These are helpful to explore its pathogenic mechanism and provide reference for disease control. [ABSTRACT FROM AUTHOR]

An experimental study on use of humidification-dehumidification (HDH) technology for treating chemical milling wastewater containing high concentrations of sodium hydroxide and sodium aluminate has been carried out. Heat pump is introduced to simultaneously supply cooling and heating loads of the HDH system. A parametric study is conducted to investigate influence of operational parameters including frequency conversion characteristics of circulating fan and pump on system performance. Performance parameters including pure water production amount (PWPA), pure water recovery rate (PWRR) and gain output ratio (GOR) are analyzed. Results indicate working frequency of pump and fan is not as high as possible, there is an optimal value. With frequency conversion of fan increases, PWPA and PWRR are increased, GOR shows a trend of first increasing and then decreasing, the optimal value of circulated air mass flow rate is 0.44 kg/s. With frequency conversion of pump increases, PWPA and GOR are increased, PWRR is decreased, the optimal value of inlet wastewater mass flow rate is 0.465 kg/s. When system is operating under optimal parameters, PWPA is 9.77 kg/h, PWRR is 0.58% and GOR is 0.781. Compare the indicators before and after treatment, pH, SS, COD, NH4-N and TP of purified water is 9.2, 4 mg/L, 53.2 mg/L, 0.028 mg/L, 0.278 mg/L, respectively. All these parameters decrease 31.9%, 97.6%, 97.5%, 77. 8%, 94.8%, respectively. Although the purified water has not yet reached the direct discharge standard or reclaimed water reuse standard, but HDH method shows feasible in the separation of highly corrosive solutions. [ABSTRACT FROM AUTHOR]

Aeromonas hydrophila infections are common in aquaculture. Our previous studies found that the A. hydrophila B11 strain can survive in fish macrophages for at least 24 h and the two‐component system EnvZ/OmpR may be involved in intracellular survival. To reveal the role and mechanism of the two‐component system EnvZ/OmpR in intracellular survival of A. hydrophila, the genes of envZ/ompR were silenced by shRNAi. The results showed that the survival rates of the envZ‐RNAi and ompR‐RNAi strains were only 2.05% and 3.75%, respectively, which were decreased by 91% and 83.6% compared with that of the wild‐type strain. The escape ability of envZ‐RNAi and ompR‐RNAi was also decreased by 51.4% and 19.7%, respectively. The comparative transcriptome analysis revealed that the functional genes directly related to bacterial intracellular survival mainly included the genes related to anti‐stress capacity, and the genes related to Zn2+ and Mg2+ transport. Further research confirmed that two‐component system EnvZ/OmpR can regulate the expression of the important molecular chaperones, such as groEL, htpG, dnaK, clpB and grpE. The expression of these molecular chaperones in wild‐type strain was up‐regulated with the increase in H2O2 concentrations, while the expression of these molecular chaperones in silent strains did not change significantly. Cells that phagocytosed wild‐type strain had higher ROS content than cells that phagocytosed silent strains. Two‐component system EnvZ/OmpR could also regulate zinc transporter (znuA, znuB, znuC) and zinc efflux protein (zntA) to maintain zinc homeostasis in cells, thus affecting the ability of bacteria to survive in phagocytes. Moreover, two‐component system EnvZ/OmpR could affect the growth and intracellular survival of A. hydrophila by regulating the expression of MgtA, MgtC and MgtE and participating in bacterial Mg2+ homeostasis in fish macrophages. [ABSTRACT FROM AUTHOR]

[Display omitted] • Active upper limb moving induce higher cortical activation than passive movement. • Cortical activation in the stroke patients was comparable to that in the healthy. • Extrinsic visual feedback leads to additional activation in the contralateral PMC/SMA. Active exercise for upper limb training has been widely used to improve hemiplegic upper limb function, and its effect may be boosted by extrinsic visual feedback. The passive movement of the hemiplegic upper limb is also commonly used. We conducted a functional near-infrared spectroscopy experiment to compare cortical activation during the following three conditions: active left upper limb movement (on the hemiplegic sides in stroke patients), with or without extrinsic motor performance visual feedback (LAV, LAnV), and passive left upper limb movement (hemiplegic sides in stroke patients) (LP) in stroke patients and healthy controls. Twenty patients with right hemispheric stroke and 20 healthy controls were recruited for this study. Hemodynamic changes were detected during left upper limb movements (on the hemiplegic sides in stroke patients) under the above three conditions in the sensorimotor cortex (SMC), supplementary motor area (SMA), and premotor cortex (PMC). There was no significant difference in the level of cortical activation between patients with stroke and healthy subjects during the three conditions. Both the LAV and LAnV induced significantly higher activation in the contralateral SMA and PMC than in the LP. Extrinsic visual feedback led to additional activation in the contralateral PMC and SMA, but this was not statistically significant. Our study indicates that active upper-limb movement appears to induce higher cortical activation than that elicited by passive movement in both stroke patients and the healthy population. Extrinsic motor performance in the form of visual feedback provided during active movement may facilitate sensorimotor areas over the contralateral hemisphere. [ABSTRACT FROM AUTHOR]

[Display omitted] A high risk of glucometabolic disorder severely disturbs compliance and limits the clinical application of olanzapine. MicroRNAs (miRNAs) in extracellular vesicles (EVs) have been reported as emerging biomarkers in glucolipid metabolic disorders. A total of 81 individuals with continuous olanzapine treatment over 3 months were recruited in this study, and plasma EVs from these individuals were isolated and injected into rats via the tail vein to investigate the glucose-regulating function in vivo. Moreover, we performed a miRNA profiling assay by high through-put sequencing to clarify the differentiated miRNA profiles between two groups of patients who were either susceptible or not susceptible to olanzapine-induced insulin resistance (IR). Finally, we administered antagomir and cocultured them with adipocytes to explore the mechanism in vitro. The results showed that individual insulin sensitivity varied in those patients and in olanzapine-administered rats. Furthermore, treatment with circulating EVs from patients with olanzapine-induced IR led to the development of metabolic abnormalities in rats and adipocytes in vitro through the AKT-GLUT4 pathway. Deep sequencing illustrated that the miRNAs of plasma EVs from patients showed a clear difference based on susceptibility to olanzapine-induced IR, and miR-486-5p was identified as a notable gene. The adipocyte data indicated that miR-486-5p silencing partially reversed the impaired cellular insulin sensitivity. Collectively, this study confirmed the function of plasma EVs in the interindividual differences in olanzapine-induced insulin sensitivity. [ABSTRACT FROM AUTHOR]

QiXian Granule (QXG) is an integrated traditional Chinese medicine formula used to treat postmenopausal atherosclerotic (AS) cardiovascular diseases. The previous studies have found that QXG inhibited isoproterenol (ISO)-induced myocardial remodeling. And its active ingredient, Icraiin, can inhibit ferroptosis by promoting oxidized low-density lipoprotein (xo-LDL)-induced vascular endothelial cell injury and autophagy in atherosclerotic mice. Another active ingredient, Salvianolic Acid B, can suppress ferroptosis and apoptosis during myocardial ischemia/reperfusion injury by reducing ubiquitin-proteasome degradation of Glutathione Peroxidase 4 (GPX4) and down-regulating the reactive oxygen species (ROS)- c-Jun N-terminal kinases (JNK)/mitogen-activated protein kinase (MAPK) pathway. The objective of this research was to assess the possible impact of QXG on atherosclerosis in postmenopausal individuals and investigate its underlying mechanisms. Female ApoE−/− mice underwent ovariectomy and were subjected to a high-fat diet (HFD) to establish a postmenopausal atherosclerosis model. The therapeutic effects of QXG were observed in vivo and in vitro through intraperitoneal injection of erastin, G-protein Coupled Estrogen Receptor (GPER) inhibitor (G15), and silent Mucolipin Transient Receptor Potential Channel 1 (TRPML1) adenovirus injection via tail vein. UPLC-MS and molecular docking techniques identified and evaluated major QXG components, contributing to the investigation of QXG's anti-postmenopausal atherosclerotic effects. QXG increased serum Estradiol levels, decreased follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, which indicated QXG had estrogen-like effects in Ovx/ApoE−/− mice. Furthermore, QXG demonstrated the potential to impede the progression of AS in Ovx/ApoE−/− mice, as evidenced by reductions in serum triglycerides (TG), total cholesterol (TC), and low-density lipoprotein-cholesterol (LDL-C) levels. Additionally, QXG inhibited ferroptosis in Ovx/ApoE−/− mice. Notably, UPLC-MS analysis identified a total of 106 active components in QXG. The results of molecular docking analysis demonstrated that Epmedin B, Astragaloside II, and Orientin exhibit strong binding affinity towards TRPML1. QXG alleviates the progression of atherosclerosis by activating TRPML1 through the GPER pathway or directly activating TRPML1, thereby inhibiting GPX4 and ferritin heavy chain (FTH1)-mediated iron pendant disease. In vitro, QXG-treated serum suppressed proliferation, migration, and ox-LDL-induced MMP and ROS elevation in HAECs. QXG inhibited GPX4 and FTH1-mediated ferroptosis in vascular endothelial cells through up-regulating GPER/TRPML1 signaling, providing a potential therapeutic option for postmenopausal females seeking a safe and effective medication to prevent atherosclerosis. The study highlights QXG's estrogenic properties and its promising role in combating postmenopausal atherosclerosis. [Display omitted] [ABSTRACT FROM AUTHOR]

The random amphiphilic polymeric aggregation, self-assembled from poly (methyl methacrylate- co -methacrylic acid) (P(MMA- co -MAA)), was explored as a novel pseudostationary phase (PSP) in electrokinetic chromatography (EKC) in our previous report. This work focused on physicochemical characteristics and PSP performances of the polymeric aggregations. The physicochemical characteristics of polymeric aggregations, including critical aggregation concentration (CAC), zeta potential, hydrodynamic diameter, and micropolarity were determined. Experimental results showed that polymeric aggregations had much lower CAC, which decreased the usage of copolymer in EKC, weakened ionic strength and shortened analysis time. The monomer molar ratio of the copolymer was a key factor for physicochemical characteristics and PSP performances of the polymeric aggregations. With the increase of the hydrophobic monomer molar ratio, CAC, micropolarity and dimension of polymeric aggregation decreased significantly while zeta potentials were similar. Correspondingly, separation window enlarged and methylene selectivity evaluated with six kinds of n-alkylphenone homologous series enhanced. Linear solvation energy relationships (LSER) analysis found that hydrophobic interaction is the most important interaction between analytes and polymeric PSPs. Compared with SDS micelle, polymeric aggregations owned more types of interactions, such as stronger hydrogen bonding and relative larger dipole interaction, which provided a bigger adjustment room to improve PSP selectivity. [ABSTRACT FROM AUTHOR]

Rheumatic heart disease (RHD) is the most common acquired heart disease among children in developing countries. However, there is a lack of systematic studies on the epidemiology of pediatric RHD. This study aimed to report the burden of pediatric RHD at global, regional, and national levels between 1990 and 2019, which may provide some reference for policymakers. The numbers and age-standardized rates (ASRs) of incidence, prevalence, mortality, and disability-adjusted life years (DALYs) for childhood RHD from 1990 to 2019 were analyzed based on data obtained from the Global Burden of Disease Study 2019 (GBD 2019). In addition, Joinpoint regression analysis was used to assess temporal trends in the burden of childhood RHD. Globally, the number of incidence and prevalence cases of RHD in children increased by 41.89% and 40.88%, respectively, from 1990 to 2019. Age-standardized incidence rate (ASIR) and age-standardized prevalence rate (ASPR) increased with an average annual percentage change (AAPC) of 0.75% and 0.66%, respectively. In contrast, the age-standardized DALY rate and age-standardized mortality rate (ASMR) decreased significantly since 1990 by an AAPC of −3.47% and − 2.65%, respectively. Girls had a significantly higher burden of RHD than boys during the study period. At the age level, the RHD burden was significantly highest in the age group of 10–14 years. Moreover, the ASRs of incidence, prevalence, mortality, and DALYs were negatively associated with sociodemographic index (SDI). Nationally, Fiji had the most significant increase in incidence and prevalence, and Philippines had the most remarkable rise in DALYs and mortality rates. From 1990 to 2019, although the incidence and prevalence of childhood RHD increased globally, DALYs and mortality rates markedly reduced. Countries with lower levels of sociodemographic development shoulder a higher burden of childhood RHD. Children aged 10–14 years are critical populations for whom targeted measures are needed to reduce the RHD burden, while attention to girls cannot be neglected. • This paper is the first to report the epidemiology of RHD in children at multiple levels including global, regional, and national. • The statistical analysis was performed by using the GBD database, so the results of the study have authenticity, reliability, and comprehensiveness. • The results of the analysis in this study were visualized, which clearly and visually demonstrates the current status and trends of RHD prevalence, and other conditions. [ABSTRACT FROM AUTHOR]

Objective: The present study aimed to evaluate the efficacy and safety of aripiprazole once-monthly (AOM) compared to oral aripiprazole in treating acute schizophrenia. Methods: This randomized, double-blind, non-inferiority study recruited patients from 15 trial sites across China from May 2017 to April 2019. Patients with an acute psychotic episode received AOM at 400 mg or oral aripiprazole at 10–20 mg for 12 weeks. The primary and secondary efficacy endpoints were the difference in scores from baseline to week 10, as assessed on the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impressions—Severity (CGI-S) scores, respectively. Results: A total of 436 patients were randomized. Among them, 159/218 (72.9%) and 165/218 (75.7%) in the AOM and oral aripiprazole groups completed 10 weeks of treatment, respectively. The least-squares (LS) mean changes from baseline to endpoint (week 10) in PANSS were − 33.6 for the AOM group and − 34.8 in the oral aripiprazole group, respectively, with a difference of − 1.2 (95% CI: − 4.1, 1.7). The non-inferiority margin of AOM to oral aripiprazole was − 4.1, which was above the lower limit of the pre-defined margin. The altered CGI-S score was − 2.2 and − 2.3 in the AOM and oral aripiprazole groups, respectively. The incidence of treatment-emergent adverse events (TEAEs) was similar in both groups. The rate of discontinuation due to TEAEs was 2.3% and 3.2% in the AOM and oral aripiprazole groups, respectively. Conclusions: This study confirmed the efficacy and safety of AOM for the treatment of Chinese patients with acute schizophrenia. The non-inferiority of AOM to oral aripiprazole was established, with comparable efficacy and tolerability. These findings suggested that AOM could be used as a treatment option for patients experiencing an acute episode of schizophrenia. Trial registration: ClinicalTrials.gov identifier: NCT03172871. [ABSTRACT FROM AUTHOR]

Background: Trace elements function as essential cofactors that are involved in various biochemical processes in mammals. Autophagy is vital for nutrient supplement, which is an important Zeitegber for the circadian homeostasis in heart. Here, we considered the possibility that autophagy, as well as the cardiomyocyte clock and glycolysis are interlinked. Detrimental effects were observed when cardiac system is exposed to bromine containing drugs. This study investigated the effects and mechanisms of bromide on the circadian clock and glycolytic metabolism of H9C2 cardiomyocytes. Results: In the present study, bromide does not affect cell viability and apoptosis of H9C2 cardiomyocytes. Bromide dampens the clock and glycolytic (Hk2 and Pkm2) gene expression rhythmicity in a dose-dependent manner. Additionally, bromide inhibits autophagic process in H9C2 cardiomyocytes. In contrast, rapamycin (an autophagy inducer) dramatically restores the inhibitory effect of NaBr on the mRNA expression levels of clock genes (Bmal1, Cry1 and Rorα) and glycolytic genes (Hk2 and Pkm2). Conclusions: Our results reveal that bromide represses the clock and glycolytic gene expression patterns, partially through inhibition of autophagy. [ABSTRACT FROM AUTHOR]

Summary: Bacterial pathogen‐host interactions are highly dynamic, regulated processes that have been primarily investigated using in vitro assays. The dynamics of bacterial pathogen‐host interplay in vivo are poorly understood. Using time‐resolved dual RNA‐seq in a Pseudomonas plecoglossicida‐Epinephelus coioides infection model, we observed that bacterial genes encoding classical virulence factors and host genes involved in immune regulation were dynamically expressed during infection. Using network inferencing, we were able to predict interspecies regulatory networks linking bacterial virulence genes to host immune genes. Together with gene co‐expression network analysis of the pathogen, secY was predicted to be a key virulence gene for P. plecoglossicida pathogenicity in the host, fliN was predicted to be a less important virulence gene. The results of bioinformatics prediction were confirmed by animal infection experiments. Our work provides the first paradigm to study dynamic alterations of bacterial pathogen and host interactions based on the elucidation of time‐resolved interactive transcriptomes in vivo, and may be developed into a novel and universal method for revealing the true complexity of the bacterial infection process. [ABSTRACT FROM AUTHOR]

Pseudomonas plecoglossicida is a Gram-negative aerobic bacterium that causes high mortality and serious economic losses in some commercial marine fish. Expression of secY was found to be significantly upregulated at 18 °C compared to 28 °C by RNA-seq and qRT-PCR. All five tested recombinant vectors (pCM130/tac + shRNA) significantly reduced secY mRNA levels in P. plecoglossicida. The recombinant vector encoding shRNA-1165 exhibited the best gene-silencing efficiency, 82.4% and was used to create an RNAi strain for further studies. Compared with the wildtype strain, infections of Larimichthys crocea with the RNAi strain resulted in a 2-day delay in onset time and a 35% reduction in mortality, as well as the alleviation of spleen symptoms. The spleens of L. crocea infected by the wild type or RNAi strain of P. plecoglossicida were subjected to dual RNA-seq at 2 dpi. Compared with the wildtype strain, infection of P. plecoglossicida with the RNAi strain resulted in significant changes in the transcriptomes of both host and pathogen. KEGG analysis showed that the complement and coagulation cascade and the Toll-like receptor signalling pathway were the most enriched host pathways. In the pathogen, genes of the "Sec secretion system" were significantly downregulated. This downregulation of "Sec secretion system" genes hindered the secretion of bacterial proteins and reduced the virulence of P. plecoglossicida. Thus, it was easier for L. crocea to clear the RNAi strain of P. plecoglossicida , and the immune response was similarly reduced. The results indicated that secY was a virulence gene of P. plecoglossicida and played roles in the host-pathogen interactions of L. crocea and P. plecoglossicida. • RNAi significantly reduced the content of secY mRNA in P. plecoglossicida. • RNAi of secY significantly reduced the pathogenicity of P. plecoglossicida. • RNAi of secY significantly altered the immune response of L. crocea. [ABSTRACT FROM AUTHOR]

Large yellow croaker (Larimichthys crocea) is an economical important farmed fish in China. "Visceral White Spot Disease" caused by Pseudomonas plecoglossicida is a disease with a high mortality rate in cage-cultured L. crocea in recent years and resulted in heavy economy lossess. The dual RNA-seq results of previous study showed that the expression of clpV gene in P. plecoglossicida was significantly up-regulated during infection. RNAi significantly reduced the expression of clpV in P. plecoglossicida with maximum silencing efficiency of 96.1%. Compared with the wild type strain, infection of clpV -RNAi strain resulted in a delayed onset time and a 25% reduction in mortality of L. crocea , as well as lessening the symptoms of the spleen. The results of dual RNA-seq of L. crocea infected by clpV -RNAi strain of P. plecoglossicida changed considerably, compared with the counterpart infected with the wild strain. The KEGG enrichment analysis showed that Cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, C-type lectin receptor signaling pathway and MAPK signaling pathway of L. crocea were most affected by the silence of clpV in P. plecoglossicida. RNAi of clpV resulted in the downregulation of genes in flagella assembly pathway and a weaker immune response of host. • RNAi significantly reduced the expression of Pseudomonas plecoglossicida clpV gene. • Dual RNA-seq simultaneously monitored host and pathogen transcriptome in a sample. • The immune response of large yellow croaker to the infection clpV -RNAi strain was weaker. • RNAi of clpV down-regulated the expression of flagella assembly pathway genes. [ABSTRACT FROM AUTHOR]

• Dissolved carbon mainly migrates downward from SKF under light rainfall events. • Dissolved carbon is mainly lost from the soil surface under heavy rainstorms. • Rainfall duration and amount mainly affect the concentration of dissolved carbon fractions. • The loss of dissolved carbon components is mainly regulated by runoff volume. Soil carbon in karst critical zones is an essential part of the global carbon pool, and the migration of dissolved carbon is a vital component of the carbon cycle in such regions. The unique "dual hydrological structure" makes the path and process of migration of soil dissolved carbon driven by rainfall unclear in karst slopes, which ultimately hinders the accurate evaluation of the carbon sink effect in such regions. Therefore, based on field monitoring of natural rainfall, this study evaluated the process and characteristics of the spatial migration of soil dissolved carbon in bare karst slopes and its response to natural rainfall (rainfall duration and amount). The results showed that the concentration of dissolved carbon transported in surface runoff was significantly lower than that transported within the soil layer; however, carbon loss displayed the opposite trend. Rainfall factors (rainfall amount and duration) and runoff volume significantly affected soil dissolved carbon, contributing 46.91% to soil dissolved carbon. Rainfall factors significantly affect soil dissolved carbon migration by influencing runoff. In addition, the hydrological path is an important factor affecting soil dissolved carbon transport. Our study shows that the soil and bedrock interface (SBI) and shallow karst fissures (SKF) are the main routes of dissolved carbon migration in soils in bare karst slopes. Dissolved carbon migrating along SKF is a vital contributor to the "missing carbon sink" in karst regions, and dissolved carbon migrating along the SBI is potentially an important contributor to the "missing carbon sink." This study provides primary data and is expected to serve as a reference for revealing the mechanism of karst carbon migration and transformation and accurately evaluating the carbon sink effect in karst areas. [ABSTRACT FROM AUTHOR]

Pseudomonas plecoglossicida is well-known as the cause of viscera granulomas disease in fish. In this study, a cspA1 knock-down strain was constructed and tested in Epinephelus coioides to observe the changes in virulence and evaluate its potential as an attenuated live vaccine. The results showed that the cspA1 knock-down strain caused a significant reduction in the ability of biofilm formation, motility, adhesion and virulence. E. coioides vaccinated with cspA1 knock-down strain were more tolerant of the infection by wild-type P. plecoglossicida. The relative percent survival value of E. coioides vaccinated with cspA1 knock-down strain reached 80% after challenging with wild-type P. plecoglossicida. In the meanwhile, the expression level of genes associated with immunity, including IL-1β, IgM, MHC-I and MHC-II, was up-regulated after vaccination, indicating that the cspA1 knock-down strain can induce effective and durable immune response in E. coioides and it may be an effective attenuated live vaccine candidate for the prevention of infections by P. plecoglossicida. • Pseudomonas plecoglossicida is a temperature dependent bacterial pathogen in fish. • cspA1 is sensitive to temperature and critical for P. plecoglossicida virulence. • cspA1 is a target for constructing P. plecoglossicida live attenuated vaccine. [ABSTRACT FROM AUTHOR]

As an important pathogen in aquaculture, Pseudomonas plecoglossicida has caused heavy losses. It was determined with RNA-seq that the expression of a LysR-type transcriptional regulator gene (L321_20267) of P. plecoglossicida at 18 °C was significantly higher than that at 28 °C, which was verified by quantitative real-time PCR (qRT-PCR). RNAi significantly reduced the content of L321_ 20267 mRNA in P. plecoglossicida , with a maximal decrease of 90.63%. Compared with the wild-type strain, infection with the L321_20267- RNAi strain resulted in a 50% reduction in mortality and an onset time delay of Epinephelus coioides , as well as alleviation of the symptoms in E. coioides spleens. Compared with the wild-type strain of P. plecoglossicida , the L321_20267- RNAi strain resulted in a significant change in the spleen transcriptome of infected E. coioides. The results of GO and KEGG analysis showed that genes of serine hydrolase activity, the antigen processing and presentation pathway, the B cell receptor signalling pathway and the chemokine signalling pathway were most affected by the L321_20267 gene of P. plecoglossicida. Meanwhile, the immune genes were related to different numbers of miRNAs and lncRNAs, and some miRNAs were related to more than one gene. The results indicated that 1. L321_20267 is a virulence gene of P. plecoglossicida ; 2. the upregulation of the immune pathways facilitated E. coioides to remove the L321_20267 -RNAi strain compared with the wild-type strain of P. plecoglossicida ; and 3. the immune genes were regulated by miRNA and lncRNA in a complex manner. • The content of L321_ 20267 mRNA of P. plecoglossicida was significantly reduced by RNAi. • The pathogenicity of P. plecoglossicida to E. coioides was significantly reduced by RNAi of the L321_20267 gene. • RNAi of the L321_20267 gene significantly upregulated immune pathways in E. coioides infected with P. plecoglossicida. • The expression of immune genes was regulated by miRNA and lncRNA in a sophisticated manner. [ABSTRACT FROM AUTHOR]

Survival in host macrophages is an effective strategy for pathogenic bacteria to spread. Aeromonas hydrophila has been found to survive in fish macrophages, but the mechanisms remain unknown. In this paper, the roles and possible mechanisms of IcmF in bacterial survival in fish macrophages were investigated. First, a stable silencing strain icmF‐RNAi was constructed by shRNA and RT‐qPCR confirmed the expression of icmF was down‐regulated by 94.42%. The expression of Hcp, DotU and VgrG was also decreased in icmF‐RNAi. The intracellular survival rate of the wild‐type strain was 92.3%, while the survival rate of icmF‐RNAi was only 20.58%. The escape rate of the wild‐type strain was 20%, while that of the icmF‐RNAi was only 7.5%. Further studies indicated that the expression of icmF can significantly affect the adhesion, biofilm formation, motility and acid resistance of A. hydrophila, but has no significant effect on the growth of A. hydrophila even under the stress of H2O2. The results indicated that IcmF of A. hydrophila not only acts as a structural protein which participates in virulence‐related characteristics such as bacterial motility, adhesion and biofilm formation, but also acts as a key functional protein which participates in the interaction between bacteria and host macrophages. [ABSTRACT FROM AUTHOR]

Abstract Several bacteria have been defined as extracellular pathogens; however, in recent years, it has been confirmed that they have the ability to survive and escape the attack of host phagocytes, thus causing further infection. Previous studies have shown that Aeromonas hydrophila could survive in fish macrophages; however, the mechanism remains unknown. In this study, sodA and sodB of the strain A. hydrophila B11 were stable silenced by shRNA. The survival rates of intracellular sodA- RNAi and sodB- RNAi decreased by 91.8% and 74.9% and the immune escape rates decreased by about 32% and 92% respectively. At the same time, reactive oxygen species (ROS) in fish macrophages that phagocytosed sodA -RNAi and sodB -RNAi increased by 40% and 32.6%, respectively, compared to those of macrophages that phagocytosed the wild-type strain. Compared to sodA, the expression of sodB predominates in A. hydrophila without oxidative stress; however, when exposed to oxidative stress, the magnitude of up-regulation of sodA expression is significantly higher than that of sodB. With increased of methyl viologen concentration, the survival rates of sodA -RNAi and sodB -RNAi were significantly decreased. The expressions of sodA and s odB did not affect the growth of A. hydrophila without oxidative stress, but the inhibition of sodA and sodB expression led to a slight decrease in bacterial growth under oxidative stress. These results indicated that (1) sodA and sodB play an important role in the process of bacterial resistance to ROS damage in host phagocytic cells, allowing them to survive or even escape fish macrophages; (2) the sodB expression was dominant in A. hydrophila without oxidative stress, the sodA expression was up-regulated more significantly under oxidative stress, and sodA and s odB contributed equally to the process of bacterial resistance to ROS; (3) sodA and sodB complement each other and cooperate in the process of intracellular survival of bacteria to protect against ROS damage. Highlights • sodA and sodB affect the process of A. hydrophila survival in fish macrophages. • The expression of sodB was dominant without oxidative stress. • Under oxidative stress, the expression of sodA was up-regulated more significantly. • sodA and sodB contributed equally to the process of bacterial resistance to ROS. • sodA and sodB complement and cooperate in the intracellular survival of bacteria. [ABSTRACT FROM AUTHOR]

Pseudomonas plecoglossicida is associated with multiple fish diseases, and temperature is one of the most important environmental factors related to its outbreak. To elucidate the influence of temperature variation on the pathogen, the global metabolomics of P. plecoglossicida (NZBD9) were analysed at the virulent (18°C) and avirulent (12°C and 28°C) temperatures. The result showed that the levels of Phosphoric acid, Tyrosine, Spermidine and Sucrose were significantly reduced，while Itaconic acid, Glucaric acid and Isomaltose were increased in P. plecoglossicida at 18°C. These metabolic adjustments assist P. plecoglossicida to survive in adverse environments, proliferate in the host, colonize and resist host immune clearance during the initial steps of infection. The results suggested that L321_03626 and L321_18122 genes played a key role in the regulation of these metabolic adaptions and thus regulated P. plecoglossicida virulence at virulent temperature, which was proved by further gene silencing and artificial infection. The present study, for the first time, determines the P. plecoglossicida metabolomic responses to temperature variation, which is helpful to explore its pathogenic mechanism and provides reference for disease control. [ABSTRACT FROM AUTHOR]

Aquaculture suffers from a number of diseases caused by Aeromonas hydrophila. Biofilm can protect bacteria from antibiotic therapy. To identify the genes those play crucial roles in A. hydrophila biofilm formation, a library of mini-Tn10 transposon insertion mutants of A. hydrophila B11 has been constructed, and 10 mutants were subjected to biofilm formation assay. The biofilm formation ability of mutant (B188) was significantly decreased compared with B11. The DNA sequence flanking the mini-Tn10 transposon inserted showed that an ORF of approximately 576 bp of the mutant strain B188 was inserted. This ORF putatively displays the highest identity (92%) with the cytochrome c4 gene (cyt-c4) of A. hydrophila subsp. hydrophila ATCC 7966. Silencing cyt-c4 led to deficiencies in biofilm formation, adhesion, drug resistance and pathogenicity of A. hydrophila, which suggests that cyt-c4 plays crucial role in the biofilm formation and virulence mechanisms of A. hydrophila. ABBREVIATIONS: GEN: gentamycin; SDZ: sulfadiazine; AK: amikacin; P: penicillin; CFP: cefoperazone; LEV: levofloxacin; MH: minocycline; FFC: florfenicol; TE: tetracycline; AMP: ampicillin; KAN: kanamycin; STR: streptomycin; SXT: sulfamethoxazole/trimethoprim; DO: doxycycline; OT: Oxytetracycline. [ABSTRACT FROM AUTHOR]

The success of the pathogenic bacteria is partly attributable to their ability to thwart host innate immune responses, which includes resisting the antimicrobial functions of macrophages. And reactive oxygen species (ROS) is one of the most effective antimicrobial components of macrophages to kill invading bacteria. Our previous studies found that Aeromonas hydrophila can survive in fish macrophages, which suggested that this bacterium might take fish macrophages as their shelters to resist drug killings and other immune damage. But how A . hydrophila survive in host macrophages remains unknown. Since KatG has been reported to have not only catalase activity but also peroxidase and peroxynitritase activity, the amino acid sequence and protein structure of KatG was analyzed in this study, the function of KatG in A . hydrophila survival in and escape from host macrophages was also carried out. The bioinformatics analysis displayed that KatG of A . hydrophila B11 showed >93% homologous to that of KatG in other Aeromonas . KatG of A . hydrophila was stable silenced by shRNA and RT-qPCR confirmed the expression of KatG in KatG -RNAi was significantly reduced. The survival rate of intracellular KatG -RNAi decreased by 80% compared to that of the wild type strain B11, while the intracellular ROS level of the macrophages that phagocytosed KatG -RNAi increased 65.9% when compared to that of the macrophages phagocytosed wild-type strain. The immune escape rate of A . hydrophila decreased by 85% when the expression of KatG was inhibited. These results indicated that (1) The amino acid sequence and protein structure of KatG of A . hydrophila is conserved; (2) KatG helped A . hydrophila to survive in fish macrophages by eliminating the harm of intracellular H 2 O 2 and inhibiting intracellular ROS levels increased; (3) A small portion of intracellular A . hydrophila could escape from host macrophages for further infection, in this process KatG also played important role. [ABSTRACT FROM AUTHOR]

Based on the free volume, shear transformation zone and percolation theory, a new percolation model has been established to investigate the ductile-brittle transition in amorphous alloys. Taking the binary Cu 25 Zr 75 amorphous alloy for example, the influence of the free volume concentration and flow unit dispersity on its percolation threshold value was analyzed. The results show that the concentration of flow units reach a critical value when the ductile-brittle transition occurs in the Cu 25 Zr 75 amorphous alloy, and this critical value is independent of the concentration of the free volume but dependent on the dispersity of flow units. Furthermore, the percolation threshold values of La-, Zr-, Cu-, Pd-, Fe-, Sr- and Tm-based amorphous alloys were also calculated, a percolation threshold value of ~0.516 for ductile-brittle transition in these amorphous alloys was obtained. Therefore, our analysis results suggest that ~0.516 appears to be a universal percolation threshold value for ductile-brittle transition in amorphous alloys. [ABSTRACT FROM AUTHOR]

The experimental and theoretical researches have been carried out to get the flow boiling heat transfer characteristics of carbon dioxide (CO 2 or R744) as a refrigerant in horizontal mini-channel. Based on infrared thermal imaging tests and experimental studies on heat transfer coefficients, the heat transfer coefficients and dryout characteristics of CO 2 are analyzed qualitatively and quantitatively in following conditions: Heat flux: 2~35 kW m -2 , Mass flux: 50~1350 kg m -2 s -1 , saturation temperature: −10~15 °C, mini-channel inner diameter: 1 mm and 2 mm. Primary conclusions can be drawn from the results of the experiments: The increase of heat flux enhances the nucleate boiling heat transfer of the refrigerant inside mini-channel, which leads to the remarkable increase of heat transfer coefficient. But it speeds up the process of dryout. It also has a certain influence on vapor qualities of dryout at both the starting and the ending stage. The effect of mass flux on heat transfer enhancement depends on the dominant heat transfer mode in the tube. With the increase of mass flow rate, the vapor quality at the start of dryout has a decreasing trend. But the heat transfer coefficient increases at the end of dryout process or even after dryout process; the heat transfer coefficient does not vary monotonically with the saturation temperature: when the saturation temperature is high and even close to CO 2 's critical temperature, the heat transfer coefficient increases with the increase of saturation temperature; when the saturation temperature is low, the heat transfer coefficient increases with the decrease of saturation temperature. Besides, during the heat transfer process, the dryout vapor quality falls monotonically with the increase of saturation temperature. It is reasonable to conclude that dryout characteristics have significant influence on heat transfer coefficient. Fang correlation that predicts the heat transfer coefficient of CO 2 is in good agreement with the experimental data, which has a mean absolute deviation of 15.7%, and predicts 71.98% of the entire database within ±20% and 86.84% of the entire database within ±30%. [ABSTRACT FROM AUTHOR]

This paper presents an experimental and theoretical investigation on two-phase flow boiling heat transfer with carbon dioxide (CO 2 or R744) as the refrigerant in horizontal small diameter tube at low temperature. The experimental data were obtained in the following condition, the heat flux is 7.5–30 kW/m 2 ; the mass flow rate is 300–600 kg/m 2 s; the saturation temperature is 233–273 K; the test section is made of stainless steel tubes whose inner diameters are 0.6 and 1.5 mm. The experimental results show that heat transfer coefficient increases with the increase of mass flow rate, but decreases with the increase of tubes’ inner diameter and saturation temperature, the boiling heat transfer of CO 2 has a greater effect on nucleate boiling and highly depends on heat flux. The comparative study indicates that: during the existed flow boiling heat transfer model, the model which has the best prediction accuracy presented with 79.8% of predicted points within ±30% and 21.8% mean deviation before the dryout phenomenon happened, while it was only 18.4% and 59.9% after the dryout phenomenon happened. [ABSTRACT FROM AUTHOR]

Adhesion to host surface or cells is the initial step in bacterial pathogenesis, and the adhesion mechanisms of the fish pathogenic bacteria Aeromonas hydrophila were investigated in this study. First, a mutagenesis library of A. hydrophila that contained 332 random insertion mutants was constructed via mini-Tn10 Km mutagenesis. Four mutants displayed the most attenuated adhesion. Sequence analysis revealed that the mini-Tn10 insertion sites in the four mutant strains were flgC (GenBank accession numbers KX261880), cytb4 (GenBank accession numbers JN133621 ), rbsR (GenBank accession numbers KX261881) and flgE (GenBank accession numbers JQ974982 ). To further study the roles of flgC and flgE in the adhesion of A. hydrophila , some biological characteristics of the wild-type strain B11, the mutants M121 and M240, and the complemented strains C121 and C240 were investigated. The results showed that the mutation in flgC or flgE led to the flagellar motility of A. hydrophila significant reduction or abolishment. flgC was not necessary for flagellar biosynthesis but was necessary for the full motility of A. hydrophila , flgE was involved in both flagellar biosynthesis and motility. The flagellar motility is necessary for A. hydrophila to adhere to the host mucus, which suggests flagellar motility plays crucial roles in the early infection process of this bacterium. [ABSTRACT FROM AUTHOR]

Introduction This study evaluated the effectiveness and safety of amisulpride in Chinese schizophrenia patients. Methods A multicenter, single-arm Phase IV study (NCT01795183). Chinese patients with schizophrenia received amisulpride for 8 weeks. The primary endpoint was ≥50% decrease in Positive and Negative Syndrome Scale total score from Baseline to Week 8. Results A total of 316 patients were enrolled; 295 were included in the effectiveness analysis; 66.8% (197/295) achieved ≥50% decrease in Positive and Negative Syndrome Scale total score from Baseline to Week 8. Nine patients discontinued treatment because of adverse events. Discussion Amisulpride had clinical effectiveness and was relatively well tolerated in Chinese patients with schizophrenia. [ABSTRACT FROM AUTHOR]

• An efficient Z-scheme CdSe/ZnIn 2 S 4 photocatalyst was successfully synthesized. • CdSe/ZnIn 2 S 4 composite with 1 % CdSe had the optical TC degradation efficacy. • Overdose of CdSe QDs resulted in a deterioration of TC degradation efficiency. • It confirmed h+ and ·O 2 – played major roles in the TC degradation process. ZnIn 2 S 4 as an energy band narrow photocatalyst has attracted extensive attentions in water remediation, but the fast carrier recombination efficiency hinders its further utilization. An effective strategy is to boost photocarrier separation and enhance photocatalysis performance by building heterojunction. Here, a simple in-situ deposition method is used to create a unique CdSe/ZnIn 2 S 4 heterojunction structure. By varying the CdSe content, CdSe/ZnIn 2 S 4 composites can be synthesized with diffident photocatalytic properties. The optimal photocatalytic efficiency of CdSe/ZnIn 2 S 4 composite is obtained when 1.0 % CdSe addition, while an overdose of CdSe QDs results in a deterioration of photocatalytic efficiency. 93 % tetracycline (TC) degradation could be attained. And the degradation rate is 1.9 and 2.3 times higher than pure ZnIn 2 S 4 and CdSe. In addition, the CdSe/ZnIn 2 S 4 photocatalytic mechanism complies with the Z-Scheme. In the photodegradation process, the superoxide radicals (·O 2 –) and holes (h+) are the primary active agents. [ABSTRACT FROM AUTHOR]

• Under the action of concentrated flow, the change of surface runoff of karst gently sloping farmland is mainly controlled by the magnitude of concentrated flow. • Under the action of concentrated flow, the underground runoff of karst gentle slope farmland is significantly negatively correlated with the slope. • Concentrated flow can lead to severe soil erosion in karst gently sloping farmland. Exposed bedrock in karst areas considerably alters runoff paths causing partial runoff to converge into a concentrated flow, which is a potential source of soil erosion risk. However, research is lacking on how concentrated flow affects regional soil erosion. In this study, the surface and underground dual structure in karst areas was simulated in a steel tank. Combined with runoff plot monitoring, the runoff conversion process and erosion characteristics of gently sloping farmland in karst areas under different water discharge rates were examined through indoor concentrated flow discharge scouring tests, and the influence of concentrated flow changes on the runoff spatial distribution and sediment yield in gently sloping farmland was clarified. The results demonstrated the following: (i) there existed a significant positive correlation between surface runoff and the water discharge rate (p < 0.01); the partial correlation coefficient value reached 0.87. The higher the water discharge rate, the more surface runoff formation was facilitated. (ii) When the slope remained the same, the underground runoff was relatively high at 3 L/min. Given the same discharge, a significant negative correlation between underground runoff and slope was found (p < 0.05); the partial correlation coefficient value reached −0.71. (iii) In response to a water discharge rate of 5 L/min, surface soil erosion was serious, and the maximum sediment transport modulus was 174.088 g/min∙m2. A significant cubic function relationship existed between the scouring time and surface sediment yield. Overall, a critical flow rate occurred between 3 and 5 L/min, which controlled changes in surface runoff, subsurface runoff and surface sediment yield. Under highly concentrated flow, drastic soil erosion could occur. These results can provide a scientific basis for the control and prevention of concentrated flow-induced erosion in karst areas. [ABSTRACT FROM AUTHOR]

A. hydrophila is one of the most important pathogens in the aquaculture industry, and its drug-resistant strains continue to emerge due to the irregular use of drugs. Previous studies found A. hydrophila could survive in fish macrophages, so it was speculated that A. hydrophila may hide in host macrophages to escape the killing of drugs and other antibacterial factors. The mechanism of A. hydrophila survival in fish macrophages is worthy of further study. In this study, the expression of a FeoC-like LuxR-type regulator was stable silenced by shRNA to construct the silencing strain feoC -RNAi. And the intracellular survival rate of feoC -RNAi decreased by about 67.5% compared with that of the wild-type strain. Comprehensive transcriptome analysis suggested that this FeoC-like LuxR-type regulator may regulate at least 1286 genes. According to GO and KEGG analysis of these 1286 DEGs, it can be speculated that this regulator may affect A. hydrophila intracellular survival by regulating bacterial metal ion metabolism, chemotaxis, type IV pilus biogenesis and binding, then further regulate the bacterial intracellular survival. Further comparison on biological phenotype of A. hydrophila B11 and feoC -RNAi revealed this FeoC-like LuxR-type regulator could regulate the expression of genes related to iron and magnesium metabolism and greatly affect bacterial growth under the limited magnesium concentration, but has no effect on bacterial growth under the limited iron concentration. And inhibited expression of this FeoC-like LuxR-type regulator led to a decrease in chemotactic ability of A. hydrophila by about 60%, disappearance of pilus, and a decrease in adhesion by about 50%. So a conclusion could be made that this FeoC-like LuxR-type regulator might play a vital role in regulating the uptake of magnesium and the homeostasis of magnesium and iron, and chemotaxis, type IV pilus biogenesis and adhesion of A. hydrophila, then further protect bacteria from the microbicidal actions and keep survival in host macrophages. • A FeoC-like LuxR-type regulator greatly affected intracellular survival of A. hydrophila. • This FeoC-like LuxR-type regulator can regulate the homeostasis of magnesium and iron in bacteria. • This FeoC-like LuxR-type regulator can also regulate bacterial chemotaxis, type IV-A pilus biogenesis and adhesion. [ABSTRACT FROM AUTHOR]

10%Cr steels are being used in steam power plant due to their excellent properties at high temperatures. Dramatically enhanced impact toughness was obtained in the welded 10%Cr rotor steel after post-weld heat treatment, increasing from 5.0J for the as-welded material to 37.5J after being heat treated at 730°C. Analysis of crystallographic structure showed that the microstructure was transformed from as-welded lath martensite to tempered martensite (treated at 670°C to 700°C), and then to high-temperature tempered martensite (treated at over 710°C). With the increase of treatment temperature, the fractography varied from brittle fracture to a fracture mode with both brittle and ductile fracture features. A small amount of M7C3 (M=Fe, Cr) particles was found in as-welded metals, while large amounts of M23C6 particles were observed in those after being treated. It is proposed that the microstructure evolution from martensitic laths in the as-welded metals to a softer ferrite matrix with the dispersion of metal carbides led to higher toughness in the post-weld heat treatment materials. [ABSTRACT FROM AUTHOR]

sigX , encoding the extracytoplasmic function sigma factor SigX, was found to be highly expressed in Pseudomonas plecoglossicida at its virulent temperature. Previous RNA-seq analysis also revealed that sigX might be a key virulence gene, which could affect the Epinephelus coioides immune response against P. plecoglossicida. Despite the necessity of sigX for virulence in P. plecoglossicida , how sigX senses and response to temperature changes, and how sigX regulates P. plecoglossicida virulence remain unclear. To illuminate these, we initially analyzed the promoter regions of the sigX and found the presence of a putative CspA box. EMSA and LacZ reporter gene analysis revealed that CspA1 is required for the expression of sigX. Consistent with a role in temperature sensing, CspA1-mediated regulation of sigX is influenced by the culture temperature. Further investigations revealed that sigX is necessary for motility and biofilm formation under virulent temperature, while cspA1 expression has been reported to be induced at virulent temperature and participate in P. plecoglossicida motility and biofilm formation regulation. Meanwhile, the intracellular survival rates and immune escape rates decreased significantly after the knockout of cspA1 and sigX. Moreover, the overlap between SigX and CspA1 regulons is very limited and only one gene is predicted to be regulated by both factors, which is identified as gabD and verified via the EMSA analysis. Together, these data suggest that CspA1 contributes to virulence in a temperature-specific manner via regulating sigX expression. • CspA1 contributes to activation of sigX in P. plecoglossicida. • sigX is important for motility, biofilm production, intracellular survival and immune escape. • CspA1 regulates virulence through activating sigX. [ABSTRACT FROM AUTHOR]

Arnebiae Radix , a common herbal medicine in China, is often utilized to treat blood-heat syndrome and has been reported to exert an effect on the heart. The combination of acetylcholine (Ach) and CaCl 2 has been widely used to induce atrial fibrillation (AF) in animals. However, whether Arnebiae Radix displays any preventive action on Ach-CaCl 2 induced AF in rats remains uncertain. In our study, we attempted to investigate the protective effects of Arnebiae Radix on Ach-CaCl 2 induced AF compared to amiodarone, which was employed as the positive control. To establish the AF model, SD rats were treated with a mixture of 0.1 mL/100 g Ach-CaCl 2 (60 μg/mL Ach and 10 mg/mL CaCl 2) by tail vein injection for 7 days. Rats were also given a gavage of Arnebiae Radix (0.18 g/mL) one week before or concurrently with the establishment of the AF model. At the end of the experimental period, the induction, duration and timing of AF were monitored using electrocardiogram recordings. Left atrial tissues were stained to observe the level of fibrosis. Electrophysiological measurements were used to examine atrial size and function. In Ach-CaCl 2 -induced AF rats, Arnebiae Radix decreased AF induction, duration and susceptibility to AF. In addition, Arnebiae Radix significantly reduced atrial fibrosis and inhibited atrial enlargement induced by Ach-CaCl 2. Moreover, there was an apparent improvement in cardiac function in the Arnebiae Radix -treated group. Our findings indicate that Arnebiae Radix treatment can attenuate Ach-CaCl 2 -induced atrial injury and serve as an effective therapeutic strategy for the treatment of AF in the future. Image 1 [ABSTRACT FROM AUTHOR]