ASA VI controls osteoarthritis in mice by maintaining mitochondrial homeostasis through Sirtuin 3.

OBJECTIVE: The aim of this study was to investigate whether ASA VI controls osteoarthritis (OA) by regulating mitochondrial function. METHODS: Primary chondrocytes were isolated and cultured from rat knee joints. The chondrocytes were treated with ASA VI and interleukin-1ß (IL-1ß) to simulate the inflammatory environment of OA. Cell viability, apoptosis, inflammatory cytokine levels, and extracellular matrix (ECM) component levels were assessed. Mitochondrial function, including ATP levels, mitochondrial membrane potential, reactive oxygen species (ROS) levels, and mitochondrial DNA content, was evaluated. The expression of Sirtuin 3 (Sirt3), a key regulator of mitochondrial homeostasis, was examined. Additionally, a rat OA model was established by destabilizing the medial meniscus, and the effects of ASA VI on cartilage degeneration were assessed. RESULTS: ASA VI treatment improved cell viability, reduced apoptosis, and decreased IL-6 and TNF-α levels in IL-1ß-induced chondrocytes. ASA VI also upregulated Collagen II and Aggrecan expression, while downregulating ADAMTS5 and MMP-13 expression. Furthermore, ASA VI mitigated IL-1ß-induced mitochondrial dysfunction by increasing ATP levels, restoring mitochondrial membrane potential, reducing ROS production, and preserving mitochondrial DNA content. These effects were accompanied by the activation of Sirt3. In the rat OA model, ASA VI treatment increased Sirt3 expression and alleviated cartilage degeneration. CONCLUSION: ASA VI exerts chondroprotective and anti-inflammatory effects on IL-1ß-induced chondrocytes by improving mitochondrial function through Sirt3 activation. ASA VI also attenuates cartilage degeneration in a rat OA model. These findings suggest that ASA VI may be a potential therapeutic agent for the treatment of osteoarthritis by targeting mitochondrial dysfunction.

Fatal Case of Naegleria fowleri Primary Amebic Meningoencephalitis from Indoor Surfing Center, Taiwan, 2023.

We investigated a fatal case of primary amoebic meningoencephalitis from an indoor surfing center in Taiwan. The case was detected through encephalitis syndromic surveillance. Of 56 environmental specimens, 1 was positive for Naegleria fowleri ameba. This report emphasizes the risk for N. fowleri infection from inadequately disinfected recreational waters, even indoors.

Proteomic Analysis of the Characteristic Flavor Components in Bacillus subtilis BSNK-5-Fermented Soymilk.

Fermentation with Bacillus subtilis significantly enhances the physiological activity and bioavailability of soymilk, but the resulting characteristic flavor seriously affects its industrial promotion. The objective of this study was to identify key proteins associated with characteristic flavors in B. subtilis BSNK-5-fermented soymilk using tandem mass tag (TMT) proteomics. The results showed that a total of 765 differentially expressed proteins were identified. Seventy differentially expressed proteins related to characteristic flavor were screened through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. After integrating metabolomics data, fifteen key proteases of characteristic flavor components in BSNK-5-fermented soymilk were further identified, and free ammonia was added. In addition, there were five main formation mechanisms, including the decomposition of urea to produce ammonia; the degradation of glutamate by glutamate dehydrogenase to produce ammonia; the degradation of threonine and non-enzymatic changes to form the derivative 2,5-dimethylpyrazine; the degradation of valine, leucine, and isoleucine to synthesize isovalerate and 2-methylbutyrate; and the metabolism of pyruvate and lactate to synthesize acetate. These results provide a theoretical foundation for the improvement of undesirable flavor in B. subtilis BSNK-5-fermented soy foods.

Improving diffuse optical tomography imaging quality using APU-Net: an attention-based physical U-Net model.

Significance: Traditional diffuse optical tomography (DOT) reconstructions are hampered by image artifacts arising from factors such as DOT sources being closer to shallow lesions, poor optode-tissue coupling, tissue heterogeneity, and large high-contrast lesions lacking information in deeper regions (known as shadowing effect). Addressing these challenges is crucial for improving the quality of DOT images and obtaining robust lesion diagnosis. Aim: We address the limitations of current DOT imaging reconstruction by introducing an attention-based U-Net (APU-Net) model to enhance the image quality of DOT reconstruction, ultimately improving lesion diagnostic accuracy. Approach: We designed an APU-Net model incorporating a contextual transformer attention module to enhance DOT reconstruction. The model was trained on simulation and phantom data, focusing on challenges such as artifact-induced distortions and lesion-shadowing effects. The model was then evaluated by the clinical data. Results: Transitioning from simulation and phantom data to clinical patients' data, our APU-Net model effectively reduced artifacts with an average artifact contrast decrease of 26.83% and improved image quality. In addition, statistical analyses revealed significant contrast improvements in depth profile with an average contrast increase of 20.28% and 45.31% for the second and third target layers, respectively. These results highlighted the efficacy of our approach in breast cancer diagnosis. Conclusions: The APU-Net model improves the image quality of DOT reconstruction by reducing DOT image artifacts and improving the target depth profile.

Insights into the role of FoxL2 in tebuconazole-induced male- biased sex differentiation of zebrafish.

Tebuconazole (TEB) is a commonly used fungicide that inhibits the aromatase Cyp19A and downregulates the transcription factor forkhead box L2 (FoxL2), leading to male-biased sex differentiation in zebrafish larvae. However, the specific mechanism by which FoxL2 functions following TEB exposure remains unclear. In this study, the phosphorylation sites and kinase-specific residues in zebrafish FoxL2 protein (zFoxL2) were predicted. Subsequently, recombinant zFoxL2 was prepared via prokaryotic expression, and a polyclonal rabbit-anti-zFoxL2 antibody was generated. Zebrafish fibroblast (ZF4) cells were exposed to 100-µM TEB alone for 8 h, after which changes in the expression of genes involved in the foxl2 regulatory pathway (akt1, pi3k, cyp19a1b, c/ebpb and sox9a) were detected. When co-exposed to 1-µM estradiol and 100-µM TEB, the expression of these key genes tended to be restored. Interestingly, TEB did not affect the expression of the foxl2 gene or protein but it significantly suppressed the phosphorylation of FoxL2 (pFoxL2) at serine 238 (decreased by 43.64 %, p = 0.009). Co-immunoprecipitation assays showed that, following exposure to 100-µM TEB, the total precipitated proteins in ZF4 cells decreased by 17.02 % (p = 0.029) and 31.39 % (p = 0.027) in the anti-zFoxL2 antibody group and anti-pFoxL2 (ser238) antibody group, respectively, indicating that TEB suppressed the capacity of the FoxL2 protein to bind to other proteins via repression of its own phosphorylation. The pull-down assay confirmed this conclusion. This study preliminarily elucidated that the foxl2 gene functions via post-translational regulation through hypophosphorylation of its encoded protein during TEB-induced male-biased sex differentiation.

Influence of leaf inclination angle and tillering on population transpiration, soil evaporation, and yield in winter wheat near-isogenic lines.

Leaf inclination angle (LIA) and tillering impact the winter wheat (Triticum aestivum L.) population canopy structure. Understanding their effects on water use (WU) parameters and yield can guide water-saving strategies through population control. In this study, six near-isogenic lines (NILs) and their parents were selected as materials. These special materials were characterized by varying tillering at the current sowing density, a similar genetic background, and, particularly, a gradient in mean flag leaf LIA. The investigation focused on the jointing to early grain-filling stage, the peak water requirement period of wheat crops. Population-scale transpiration (PT) and evaporation from the soil surface (E) were partitioned from total evapotranspiration (ET) by the means of micro-lysimeters. The results showed decreased PT, E, and ET with increased population density (PD) within a narrow density range derived from varying tillering across genotypes. Significant correlations existed between PD and ET, E, and PT, especially in the wettest 2017-2018 growing season. Within such narrow PD range, all the correlations between WU parameters and PD were negative, although some correlations were not statistically significant, thereby suggesting the population structure's predominant impact. No significant correlation existed between LIA and both ET and PT within the LIA range of 35°-65°. However, significant correlations occurred between LIA and E in two growing seasons. Genotypes with similar LIA but different PD produced varied ET; while with similar PD, the four pairs of genotypes with different LIA each consumed similar ET, thus highlighting PD's more crucial role in regulating ET. The yield increased with higher LIA, and showed a significant correlation, emphasizing the LIA's significant effect on yield. However, no correlation was observed with PD, indicating the minor effect of tillering at the current sowing density. Therefore these results might offer valuable insights for breeding water-saving cultivars and optimizing population structures for effective field water conservation.

MicroRNA-146a-5p protects retinal ganglion cells through reducing neuroinflammation in experimental glaucoma.

Neuroinflammation plays important roles in retinal ganglion cell (RGC) degeneration in glaucoma. MicroRNA-146 (miR-146) has been shown to regulate inflammatory response in neurodegenerative diseases. In this study, whether and how miR-146 could affect RGC injury in chronic ocular hypertension (COH) experimental glaucoma were investigated. We showed that in the members of miR-146 family only miR-146a-5p expression was upregulated in COH retinas. The upregulation of miR-146a-5p was observed in the activated microglia and Müller cells both in primary cultured conditions and in COH retinas, but mainly occurred in microglia. Overexpression of miR-146a-5p in COH retinas reduced the levels pro-inflammatory cytokines and upregulated the levels of anti-inflammatory cytokines, which were further confirmed in the activated primary cultured microglia. Transfection of miR-146a-5p mimic increased the percentage of anti-inflammatory phenotype in the activated BV2 microglia, while transfection of miR-146a-5p inhibitor resulted in the opposite effects. Transfection of miR-146a-5p mimic/agomir inhibited the levels of interleukin-1 receptor associated kinase (IRAK1) and TNF receptor associated factor 6 (TRAF6) and phosphorylated NF-κB subunit p65. Dual luciferase reporter gene assay confirmed that miR-146a-5p could directly target IRAK1 and TRAF6. Moreover, downregulation of IRAK1 and TRAF6 by siRNA techniques or blocking NF-κB by SN50 in cultured microglia reversed the miR-146a-5p inhibitor-induced changes of inflammatory cytokines. In COH retinas, overexpression of miR-146a-5p reduced RGC apoptosis, increased RGC survival, and partially rescued the amplitudes of photopic negative response. Our results demonstrate that overexpression of miR-146a-5p attenuates RGC injury in glaucoma by reducing neuroinflammation through downregulating IRAK1/TRAF6/NF-κB signaling pathway in microglia.

Spontaneous Molecular Bromine Production in Sea-Salt Aerosols.

Bromine chemistry is responsible for the catalytic ozone destruction in the atmosphere. The heterogeneous reactions of sea-salt aerosols are the main abiotic sources of reactive bromine in the atmosphere. Here, we present a novel mechanism for the activation of bromide ions (Br-) by O2 and H2O in the absence of additional oxidants. The laboratory and theoretical calculation results demonstrated that under dark conditions, Br-, O2 and H3O+ could spontaneously generate Br and HO2 radicals through a proton-electron transfer process at the air-water interface and in the liquid phase. Our results also showed that light and acidity could significantly promote the activation of Br- and the production of Br2. The estimated gaseous Br2 production rate was up to 1.55×1010 molecules cm-2 ⋅ s-1 under light and acidic conditions; these results showed a significant contribution to the atmospheric reactive bromine budget. The reactive oxygen species (ROS) generated during Br- activation could promote the multiphase oxidation of SO2 to produce sulfuric acid, while the increase in acidity had a positive feedback effect on Br- activation. Our findings highlight the crucial role of the proton-electron transfer process in Br2 production; here, H3O+ facilitates the activation of Br- by O2, serves as a significant source of atmospheric reactive bromine and exerts a profound impact on the atmospheric oxidation capacity.

miR-29b-triggered epigenetic regulation of cardiotoxicity following exposure to deltamethrin in zebrafish.

Deltamethrin is a classical pyrethroid insecticide that is frequently detected in aquatic environments and organisms. Furthermore, deltamethrin has been detected in samples related to human health and is a potential risk to public health. This study aimed to investigate the mechanism of cardiotoxicity induced by deltamethrin. Zebrafish were exposed to 0.005, 0.05, or 0.5 µg/L deltamethrin for 28 days. The results showed a significant reduction in male reproduction compared to female reproduction. Additionally, the heart rate decreased by 15.75 % in F1 after parental exposure to 0.5 µg/L deltamethrin. To evaluate cardiotoxicity, deltamethrin was administered to the zebrafish embryos. By using miRNA-Seq and bioinformatics analysis, it was discovered that miR-29b functions as a toxic regulator by targeting dnmts. The overexpression of miR-29b and inhibition of dnmts resulted in cardiac abnormalities, such as pericardial edema, bradycardia, and abnormal expression of genes related to the heart. Similar changes in the levels of miR-29b and dnmts were also detected in the gonads of F0 males and F1 embryos, confirming their effects. Overall, the results suggest that deltamethrin may have adverse effects on heart development in early-stage zebrafish and on reproduction in adult zebrafish. Furthermore, epigenetic modifications may threaten the cardiac function of offspring.

Single-cell transcriptome sequencing partially revealed the changes of T cells in the early stage of aging kidney.

Aging is a gradual, inevitable physiologic process. The organ aging is related to the persistence of chronic inflammation, but the understanding of inflammatory state during renal aging is lacking currently. Single-cell transcriptome sequencing was performed on aging mouse kidney to reveal the molecular phenotype and composition changes of different cell types. In the early stage of aging, immune cells such as T, B cells and mononuclear macrophages increased in kidney. The molecular state of T cells in aging kidney changed and polarized. Among them, we identified a group of GZMK+ CD8 + T cells with high expression of Eomes, Pdcd1 and Ifng and a group of Il17a+ T cells with high expression of Il17a and Il23r. Moreover, the cytokines and inflammations can aggravate tissue damage eventually. Furthermore, we found the interaction between different types of epithelial cells and T cells increased during the renal aging. These results identify the changes of T cells in the early stage of aging kidney and suggest that GZMK+CD8+ T cells might be a potential target to ameliorate age-associated dysfunctions of kidney(Graphical Abstract).

Neuroprotection of the P2X7 receptor antagonist A740003 on retinal ganglion cells in experimental glaucoma.

The aim of this study was to explore the neuroprotective effects of the P2X7 receptor antagonist A740003 on retinal ganglion cells (RGCs) in chronic intraocular hypertension (COH) experimental glaucoma mouse model. Bioinformatics was used to analyze the glaucoma-related genes. Western blot, real-time fluorescence quantitative PCR, and immunofluorescence staining techniques were employed to explore the mechanisms underlying the neuroprotective effects of A740003 on RGCs in COH retinas. Bioinformatic analysis revealed that oxidative stress, neuroinflammation, and cell apoptosis were highly related to the pathogenesis of glaucoma. In COH retinas, intraocular pressure elevation significantly increased the levels of translocator protein, a marker of microglial activation, which could be reversed by intravitreal preinjection of A740003. A740003 also suppressed the increased mRNA levels of proinflammatory cytokines interleukin (IL) 1ß and tumor necrosis factor α in COH retinas. In addition, although the mRNA levels of anti-inflammatory cytokine IL-4 and IL-10 were kept unchanged in COH retinas, administration of A740003 could increase their levels. The mRNA and protein levels of Bax and cleaved caspase-3 were increased in COH retinas, which could be partially reversed by A740003, while the levels of Bcl-2 kept unchanged in COH retinas with or without the injections of A740003. Furthermore, A740003 partially attenuated the reduction in the numbers of Brn-3a-positive RGCs in COH mice. A740003 could provide neuroprotective roles on RGCs by inhibiting the microglia activation, attenuating the retinal inflammatory response, reducing the apoptosis of RGCs, and enhancing the survival of RGCs in COH experimental glaucoma.

Exploratory and confirmatory factor analysis of the sensitivity to punishment and sensitivity to reward questionnaire-revised and its psychometric evaluation among Chinese person with substance use disorder.

The Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ) is a self-report tool widely used to assess individuals' level of reinforcement sensitivity. Drug addiction is strongly associated with reinforcement sensitivity, but there is a lack of measurement tools to assess reinforcement sensitivity in drug users, necessitating the revision and application of the SPSRQ among drug users. This study recruited 819 drug users (mean age = 34.74; 56.41% female) from five compulsory rehabilitation centers in Hunan Province, China. The applicability of the SPSRQ among person with substance use disorder was assessed by conducting reliability analyses and validity analyses, with retesting performed by 127 individuals after 6 weeks. Exploratory factor analysis for the SPSRQ showed a stable two-factor structure in person with substance use disorder. Confirmatory factor analysis indicated acceptable goodness of fit indexes for the two-factor structure. The SPSRQ also demonstrated good reliability and convergent and discriminant validity evidence. The two-factor structure of the SPSRQ also demonstrated measurement invariance across gender. Further comparative analysis found that the degree of reward sensitivity was higher for males than for females. Generally, the SPSRQ has shown evidence of good reliability and validity in Chinese drug-dependent populations, and it is suitable for research and application with Chinese person with substance use disorder. These findings about the personality traits of people with substance use disorder provide a solid basis for further research.

Integrative molecular and structural neuroimaging analyses of the interaction between depression and age of onset: A multimodal magnetic resonance imaging study.

Depression is a neurodevelopmental disorder that exhibits progressive gray matter volume (GMV) atrophy. Research indicates that brain development is influential in depression-induced GMV alterations. However, the interaction between depression and age of onset is not well understood by the underlying molecular and neuropathological mechanisms. Thus, 152 first-episode depression individuals and matched 130 healthy controls (HCs) were recruited to undergo T1-weighted high-resolution magnetic resonance imaging for this study. By two-way ANOVA, age and diagnosis were used as factors when analyzing the interaction of GMV in the participants. Then, spatial correlations between neurotransmitter maps and factor-related volume maps are established. Results illustrate a pronounced antagonistic interaction between depression and age of onset in the right insula, superior temporal gyrus, anterior cingulate gyrus, and orbitofrontal gyrus. Depression-caused reductions in GMV are mainly distributed in thalamic-limbic-cortical regions, regardless of age. For the main effect of age, adults exhibit brain atrophy in frontal, cerebellum, parietal, and temporal lobe structures. Cross-modal correlations showed that GMV changes in the interactive regions were linked with the serotonergic system and dopaminergic systems. Summarily, our results reveal the interaction between depression and age of onset in neurobiological mechanisms, which provide hints for future treatment of different ages of depression.

Gut microbiota modulation: a narrative review on a novel strategy for prevention and alleviation of ovarian aging.

The global rise in life expectancy corresponds with a delay in childbearing age among women. Ovaries, seen as the chronometers of female physiological aging, demonstrate features of sped up aging, evidenced by the steady decline in both the quality and quantity of ovarian follicles from birth. The multifaceted pathogenesis of ovarian aging has kindled intensive research interest from the biomedical and pharmaceutical sectors. Novel studies underscore the integral roles of gut microbiota in follicular development, lipid metabolism, and hormonal regulation, forging a nexus with ovarian aging. In this review, we outline the role of gut microbiota in ovarian function (follicular development, oocyte maturation, and ovulation), compile and present gut microbiota alterations associated with age-related ovarian aging. We also discuss potential strategies for alleviating ovarian aging from the perspective of gut microbiota, such as fecal microbiota transplantation and probiotics.

Cuproptosis-related lncRNA signature as a prognostic tool and therapeutic target in diffuse large B cell lymphoma.

Cuproptosis is a newly defined form of programmed cell death that relies on mitochondria respiration. Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis and metastasis. However, whether cuproptosis-related lncRNAs are involved in the pathogenesis of diffuse large B cell lymphoma (DLBCL) remains unclear. This study aimed to identify the prognostic signatures of cuproptosis-related lncRNAs in DLBCL and investigate their potential molecular functions. RNA-Seq data and clinical information for DLBCL were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Cuproptosis-related lncRNAs were screened out through Pearson correlation analysis. Utilizing univariate Cox, least absolute shrinkage and selection operator (Lasso) and multivariate Cox regression analysis, we identified seven cuproptosis-related lncRNAs and developed a risk prediction model to evaluate its prognostic value across multiple groups. GO and KEGG functional analyses, single-sample GSEA (ssGSEA), and the ESTIMATE algorithm were used to analyze the mechanisms and immune status between the different risk groups. Additionally, drug sensitivity analysis identified drugs with potential efficacy in DLBCL. Finally, the protein-protein interaction (PPI) network were constructed based on the weighted gene co-expression network analysis (WGCNA). We identified a set of seven cuproptosis-related lncRNAs including LINC00294, RNF139-AS1, LINC00654, WWC2-AS2, LINC00661, LINC01165 and LINC01398, based on which we constructed a risk model for DLBCL. The high-risk group was associated with shorter survival time than the low-risk group, and the signature-based risk score demonstrated superior prognostic ability for DLBCL patients compared to traditional clinical features. By analyzing the immune landscapes between two groups, we found that immunosuppressive cell types were significantly increased in high-risk DLBCL group. Moreover, functional enrichment analysis highlighted the association of differentially expressed genes with metabolic, inflammatory and immune-related pathways in DLBCL patients. We also found that the high-risk group showed more sensitivity to vinorelbine and pyrimethamine. A cuproptosis-related lncRNA signature was established to predict the prognosis and provide insights into potential therapeutic strategies for DLBCL patients.

The Effectiveness of the 4P Nursing Model Combined with Amisulpride and Clozapine in the Management of Psychiatric Patients.

Objective: To study the clinical effectiveness of the 4P nursing model combined with Amisulpride and Clozapine in the management of psychiatric patients. Method: 100 patients with refractory schizophrenia treated in the Psychiatry department of Ganzhou People's Hospital from January 3, 2021, to January 4, 2022, were selected as the study subjects. They were randomly divided into observation and control groups, with 50 patients in each group. The clinical efficacy in the two groups was then assessed and compared using such parameters as the PANSS score, body mass index (BMI), blood lipid levels, incidence of side effects, and nursing satisfaction scores. Results: The difference in total treatment efficacy was statistically significant (χ2=11.724, 9.458, P ≤ .001, RR0.24, 95%CI (0.117-0.363)). The post-treatment PANSS score, positive symptom score, negative symptom score, and general pathological score treatment were all lower than the pre-treatment scores in both groups. The difference was statistically significant (RR0.12, 95%CI (0.098-0.203)). There was a reduction in the BMI of patients in the observation group after treatment, while there was an increase in that of patients in the control group. However, after treatment, there were significant reductions in the concentrations of T-CHO, LDL-C, and HDL-C in both groups (all P < .05, RR0.26, 95%CI (0.156-0.371)), with more significant reductions seen in the observation group than in the control group. The patients in the observation group recorded a much lower incidence of such side effects as drowsiness, nausea and vomiting, constipation, and weight gain and were more satisfied with the nursing they received as compared to their counterparts in the control group (all P < .05, RR0.28, 95%CI (0.171-0.351)). Conclusion: The 4P nursing model combined with Amisulpride and Clozapine can improve adherence to treatment, as well as the overall effectiveness of treatment. This nursing method has a high safety profile, improves the quality of life, and its use deserves more widespread promotion.

Characterization of two virulent Salmonella phages and transient application in egg, meat and lettuce safety.

Salmonella, a prominent foodborne pathogen, has posed enduring challenges to the advancement of food safety and global public health. The escalating concern over antibiotic misuse, resulting in the excessive presence of drug residues in animal-derived food products, necessitates urgent exploration of alternative strategies for Salmonella control. Bacteriophages emerge as promising green biocontrol agents against pathogenic bacteria. This study delineates the identification of two novel virulent Salmonella phages, namely phage vB_SalS_ABTNLsp11241 (referred to as sp11241) and phage 8-19 (referred to as 8-19). Both phages exhibited efficient infectivity against Salmonella enterica serotype Enteritidis (SE). Furthermore, this study evaluated the effectiveness of two phages to control SE in three different foods (whole chicken eggs, raw chicken meat, and lettuce) at different MOIs (1, 100, and 10000) at 4°C. It's worth noting that sp11241 and 8-19 achieved complete elimination of SE on eggs after 3 h and 6 h at MOI = 100, and after 2 h and 5 h at MOI = 10000, respectively. After 12 h of treatment with sp11241, a maximum reduction of 3.17 log10 CFU/mL in SE was achieved on raw chicken meat, and a maximum reduction of 3.00 log10 CFU/mL was achieved on lettuce. Phage 8-19 has the same effect on lettuce as sp11241, but is slightly less effective than sp11241 on chicken meat (a maximum 2.69 log10 CFU/mL reduction). In conclusion, sp11241 and 8-19 exhibit considerable potential for controlling Salmonella contamination in food at a low temperature and represent viable candidates as green antibacterial agents for food applications.

[Relationship Between Cerebrovascular Reactivity and Depression in Patients With End-Stage Renal Disease].

Objective To investigate the relationship between cerebrovascular reactivity (CVR) and emotional disorders in the patients undergoing continuous hemodialysis for end-stage renal disease (ESRD).Methods The clinical data of the ESRD patients undergoing continuous hemodialysis were collected.Anxiety and depression of the patients were assessed by the Hamilton anxiety scale (HAMA) and Beck depression inventory,respectively.The cerebral hemodynamic changes during the breath holding test were monitored by transcranial Doppler sonography,and the breath-holding index (BHI) was calculated.The BHI≥0.69 and BHI<0.69 indicate normal CVR and abnormal CVR,respectively.Binary Logistic regression was employed to analyze the factors affecting the depressive state of ESRD patients.Results The group with abnormal CVR exhibited higher total cholesterol level (P=0.010),low density lipoprotein level (P=0.006),and incidence of depression (P=0.012) than the group with normal CVR.Compared with the non-depression group,the depression group displayed prolonged disease course (P=0.039),reduced body mass index (P=0.048),elevated HAMA score (P=0.001),increased incidence of anxiety (P<0.001),decreased BHI (P=0.015),and increased incidence of abnormal CVR (P=0.012).Binary Logistic regression analysis indicated anxiety as a contributing factor (OR=22.915,95%CI=2.653-197.956,P=0.004) and abnormal CVR as a risk factor (OR=0.074,95%CI=0.008-0.730,P=0.026) for depression.Conclusion Impaired CVR could pose a risk for depression in the patients with ESRD.

2D Exfoliation Chemistry Towards Covalent Pseudo-Layered Phosphate Framework Derived by Radical/Strain-Synergistical Process.

2D compounds exfoliated from weakly bonded bulk materials with van der Waals (vdW) interaction are easily accessible. However, the strong internal ionic/covalent bonding of most inorganic crystal frameworks greatly hinders 2D material exfoliation. Herein, we first proposed a radical/strain-synergistic strategy to exfoliate non-vdW interacting pseudo-layered phosphate framework. Specifically, hydroxyl radicals (⋅OH) distort the covalent bond irreversibly, meanwhile, H2O molecules as solvents, further accelerating interlayered ionic bond breakage but mechanical expansion. The innovative 2D laminar NASICON-type Na3V2(PO4)2O2F crystal, exfoliated by ⋅OH/H2O synergistic strategy, exhibits enhanced sodium-ion storage capacity, high-rate performance (85.7 mAh g-1 at 20 C), cyclic life (2300 cycles), and ion migration rates, compared with the bulk framework. Importantly, this chemical/physical dual driving technique realized the effective exfoliation for strongly coupled pseudo-layered frameworks, which accelerates 2D functional material development.

Safety and immunogenicity of a polyvalent DNA-protein HIV vaccine with matched Env immunogens delivered as a prime-boost regimen or coadministered in HIV-uninfected adults in the USA (HVTN 124): a phase 1, placebo-controlled, double-blind randomised controlled trial.

BACKGROUND: An effective HIV vaccine will most likely need to have potent immunogenicity and broad cross-subtype coverage. The aim of the HIV Vaccine Trials Network (HVTN) 124 was to evaluate safety and immunogenicity of a unique polyvalent DNA-protein HIV vaccine with matching envelope (Env) immunogens. METHODS: HVTN 124 was a randomised, phase 1, placebo-controlled, double-blind study, including participants who were HIV seronegative and aged 18-50 years at low risk for infection. The DNA vaccine comprised five plasmids: four copies expressing Env gp120 (clades A, B, C, and AE) and one gag p55 (clade C). The protein vaccine included four DNA vaccine-matched GLA-SE-adjuvanted recombinant gp120 proteins. Participants were enrolled across six clinical sites in the USA and were randomly assigned to placebo or one of two vaccine groups (ie, prime-boost or coadministration) in a 5:1 ratio in part A and a 7:1 ratio in part B. Vaccines were delivered via intramuscular needle injection. The primary outcomes were safety and tolerability, assessed via frequency, severity, and attributability of local and systemic reactogenicity and adverse events, laboratory safety measures, and early discontinuations. Part A evaluated safety. Part B evaluated safety and immunogenicity of two regimens: DNA prime (administered at months 0, 1, and 3) with protein boost (months 6 and 8), and DNA-protein coadministration (months 0, 1, 3, 6, and 8). All randomly assigned participants who received at least one dose were included in the safety analysis. The study is registered with ClinicalTrials.gov (NCT03409276) and is closed to new participants. FINDINGS: Between April 19, 2018 and Feb 13, 2019, 60 participants (12 in part A [five men and seven women] and 48 in part B [21 men and 27 women]) were enrolled. All 60 participants received at least one dose, and 14 did not complete follow-up (six of 21 in the prime-boost group and eight of 21 in the coadminstration group). 11 clinical adverse events deemed by investigators as study-related occurred in seven of 48 participants in part B (eight of 21 in the prime-boost group and three of 21 in the coadministration group). Local reactogenicity in the vaccine groups was common, but the frequency and severity of reactogenicity signs or symptoms did not differ between the prime-boost and coadministration groups (eg, 20 [95%] of 21 in the prime-boost group vs 21 [100%] of 21 in the coadministration group had either local pain or tenderness of any severity [p=1·00], and seven [33%] vs nine [43%] had either erythema or induration [p=0·97]), nor did laboratory safety measures. There were no delayed-type hypersensitivity reactions or vasculitis or any severe clinical adverse events related to vaccination. The most frequently reported systemic reactogenicity symptoms in the active vaccine groups were malaise or fatigue (five [50%] of ten in part A and 17 [81%] of 21 in the prime-boost group vs 15 [71%] of 21 in the coadministration group in part B), headache (five [50%] and 18 [86%] vs 12 [57%]), and myalgia (four [40%] and 13 [62%] vs ten [48%]), mostly of mild or moderate severity. INTERPRETATION: Both vaccine regimens were safe, warranting evaluation in larger trials. FUNDING: US National Institutes of Health and US National Institute of Allergy and Infectious Diseases.