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The pathogenesis of attention-deficit/hyperactivity disorder (ADHD) has not been fully elucidated. Gestational hypertension could double the probability of ADHD in the offspring, while the initial bacterial communication between the mother and offspring has been associated with psychiatric disorders. Thus, we hypothesize that antihypertensive treatment during pregnancy may abate the impairments in neurodevelopment of the offspring. To test this hypothesis, we chose Captopril and Labetalol, to apply to pregnant spontaneously hypertensive rat (SHR) dams and examined the outcomes in the male offspring. Our data demonstrated that maternal treatment with Captopril and Labetalol had long-lasting changes in gut microbiota and behavioral alterations, including decreased hyperactivity and increased curiosity, spatial learning and memory in the male offspring. Increased diversity and composition were identified, and some ADHD related bacteria were found to have the same change in the gut microbiota of both the dam and offspring after the treatments. LC-MS/MS and immunohistochemistry assays suggested elevated expression of brain derived neurotrophic factor (BDNF) and dopamine in the prefrontal cortex and striatum of offspring exposed to Captopril/ Labetalol, which may account for the improvement of the offspring's psychiatric functions. Therefore, our results support the beneficial long-term effects of the intervention of gestational hypertension in the prevention of ADHD. [Display omitted] • Maternal Captopril/Labetalol treatment alleviated ADHD symptoms in SHR offspring. • Maternal Captopril/Labetalol treatment altered gut microbiota in SHR offspring. • Maternal Captopril/Labetalol treatment elevated brain dopamine in SHR offspring. [ABSTRACT FROM AUTHOR]

The simultaneous circulation of seasonal influenza virus and SARS-CoV-2 variants will likely pose unique challenges to public health during the future influenza seasons. Persons who are undergoing treatment in healthcare facilities may be particularly at risk. It is important for healthcare personnel to protect themselves and patients by receiving vaccines. The purpose of this study is to assess coverage of the seasonal influenza vaccine and COVID-19 monovalent booster among healthcare personnel working at acute care hospitals in the United States during the 2021–22 influenza season and to examine the demographic and facility characteristics associated with coverage. A total of 3260 acute care hospitals with over 7 million healthcare personnel reported vaccination data to National Healthcare Safety Network (NHSN) during the 2021–22 influenza season. Two separate negative binomial mixed models were developed to explore the factors associated with seasonal influenza coverage and COVID-19 monovalent booster coverage. At the end of the 2021–2022 influenza season, the overall pooled mean seasonal influenza coverage was 80.3%, and the pooled mean COVID-19 booster coverage was 39.5%. Several demographic and facility-level factors, such as employee type, facility ownership, and geographic region, were significantly associated with vaccination against influenza and COVID-19 among healthcare personnel working in acute care hospitals. Our findings highlight the need to increase the uptake of vaccination among healthcare personnel, particularly non-employees, those working in for-profit and non-medical school-affiliated facilities, and those residing in the South. [ABSTRACT FROM AUTHOR]

Macrophages are the first-line host defense that the invading Mycobacterium tuberculosis (Mtb) encounters. It has been recently reported that host aerobic glycolysis was elevated post the infection by a couple of virulent mycobacterial species. However, whether this metabolic transition is required for host defense against intracellular pathogens and the underlying mechanisms remain to be further investigated. A pathogenic mycobacterial species, M. marinum , is genetically close to Mtb and was utilized in this study. Through analyzing cellular carbon metabolism of RAW 264.7 (a murine macrophage-like cell line) post M. marinum infection, a strong elevation of glycolysis was observed. Next, three glycolysis inhibitors were examined for their ability to inhibit mycobacterial proliferation inside RAW264.7 macrophages. Among them, a glucose analog, 2-deoxyglucose (2-DG) displayed a protective role against mycobacterial infection. Treatment with 2-DG at concentrations of 0.5 or 1 mM significantly induced autophagy and decreased the phagocytosis of M. marinum by macrophages. Moreover, 2-DG pre-treatment exerted a significantly protective effect on zebrafish larvae by limiting the proliferation of M. marinum , and such effect was correlated to tumor necrosis factor alpha (TNF-α) as the 2-DG pre-treatment increased the expression of TNF-α in both mouse peritoneal macrophages and zebrafish. On the contrary, the 2-DG treatment post infection did not restrain proliferation of M. marinum in WT zebrafish, and even accelerated bacterial replication in TNF-α−/− zebrafish. Together, modulation of glycolysis prior to infection boosts host immunity against M. marinum infection, indicating a potential intervention strategy to control mycobacterial infection. • Macrophages displayed an elevated glycolysis post M. marinum infection. • 2-DG reduced phagocytosis and M. marinum burden inside macrophages. • 2-DG pretreatment led to autophagy or apoptosis of RAW cells. • 2-DG pre-treatment inhibited the proliferation of M. marinum in WT zebrafish. • 2-DG accelerated M. marinum proliferation in zebrafish missing TNF-α. [ABSTRACT FROM AUTHOR]

By the end of 2021, approximately 15% of U.S. adults remained unvaccinated against COVID-19, and vaccination initiation rates had stagnated. We used unsupervised machine learning (K-means clustering) to identify clusters of unvaccinated respondents based on Behavioral and Social Drivers (BeSD) of COVID-19 vaccination and compared these clusters to vaccinated participants to better understand social/behavioral factors of non-vaccination. The National Immunization Survey Adult COVID Module collects data on U.S. adults from September 26–December 31,2021 (n = 187,756). Among all participants, 51.6% were male, with a mean age of 61 years, and the majority were non-Hispanic White (62.2%), followed by Hispanic (17.2%), Black (11.9%), and others (8.7%). K-means clustering procedure was used to classify unvaccinated participants into three clusters based on 9 survey BeSD items, including items assessing COVID-19 risk perception, social norms, vaccine confidence, and practical issues. Among unvaccinated adults (N = 23,397), 3 clusters were identified: the "Reachable" (23%), "Less reachable" (27%), and the "Least reachable" (50%). The least reachable cluster reported the lowest concern about COVID-19, mask-wearing behavior, perceived vaccine confidence, and were more likely to be male, non-Hispanic White, with no health conditions, from rural counties, have previously had COVID-19, and have not received a COVID-19 vaccine recommendation from a healthcare provider. This study identified, described, and compared the characteristics of the three unvaccinated subgroups. Public health practitioners, healthcare providers and community leaders can use these characteristics to better tailor messaging for each sub-population. Our findings may also help inform decisionmakers exploring possible policy interventions. • We analyzed data from the National Immunization Survey-Adult COVID Module, September–December 2021 (n = 187,756). • Three unvaccinated subgroups were identified by K-means clustering based on social/behavioral drivers of COVID-19 vaccination. • We identified a more reachable unvaccinated subgroup that might be receptive to information promoting vaccination. • COVID-19 vaccination strategies can be tailored based on the characteristics and needs of the targeted sub-populations. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the effects of PCI-34051-induced human bronchial epithelial cells (HBECs)-derived exosomes (PCI-Exo) on human bronchial smooth muscle cells (HBSMCs) and the key exosomal miRNAs involved in this process. Blank exosomes (Exo) and PCI-Exo were extracted from HBECs treated with PBS and PCI-34051, respectively. RNA-sequencing was performed to uncover the miRNA expression profile affected by PCI-Exo. The MTT, flow cytometry and TUNEL assays were performed to reveal the effect of PCI-34051 and PCI-Exo on the proliferation and apoptosis of HBSMCs. Western blotting and qRT-PCR were used for detecting protein and mRNA expression. A total of 25 exosomal miRNAs consisted of 17 down-regulated and eight up-regulated miRNAs were differentially expressed among PCI-Exo and Exo. Target genes of the exosomal miRNAs were mainly associated with signal transduction, cell adhesion, microRNAs in cancer, and ECM receptor interaction. miR-381-3p was identified as the most significant upregulated differential miRNA in PCI-Exo after qRT-PCR validation and could be transferred to HBSMCs by PCI-Exo. PCI-Exo treatment inhibited the proliferation but induced the apoptosis of HBSMCs. TGFβ3 was identified as a target gene of miR-381-3p which could directly bind to the 3′UTR of TGFβ3 mRNA. After transfecting the miR-381-3p mimic into HBSMCs, the proliferation inhibition and apoptosis rate of HBSMCs was significantly increased, and siTGFβ3 transfection showed similar effects. Moreover, miR-381-3p overexpression could not only decrease the expression of α-SMA, FN1 and collagen I but also increase that of E-cadherin in HBSMCs. Our findings suggested that PCI-Exo could hinder the proliferation and obviously induce the apoptosis of HBSMCs, and its mechanisms might partly be attributable to the reduction of TGFβ3 level by up-regulating exosomal miR-381-3p expression. These results may be vital for the treatment of lung related-diseases, especially asthma. [ABSTRACT FROM AUTHOR]

Gut dysbiosis and dysregulation of gut–brain communication have been identified in hypertensive patients and animal models. Previous studies have shown that probiotic or prebiotic treatments exert positive effects on the pathophysiology of hypertension. This study aimed to examine the hypothesis that the microbiota-gut-brain axis is involved in the antihypertensive effects of curcumin, a potential prebiotic obtained from Curcuma longa. Male 8- to 10-week-old spontaneously hypertensive rats (SHRs) and Wistar Kyoto (WKY) rats were divided into four groups: WKY rats and SHRs treated with vehicle and SHRs treated with curcumin in dosage of 100 or 300 mg/kg/day for 12 weeks. Our results show that the elevated blood pressure of SHRs was markedly decreased in both curcumin-treated groups. Curcumin treatment also altered the gut microbial composition and improved intestinal pathology and integrity. These factors were associated with reduced neuroinflammation and oxidative stress in the hypothalamus paraventricular nucleus (PVN). Moreover, curcumin treatment increased butyrate levels in the plasma, which may be the result of increased butyrate-producing gut microorganisms. In addition, curcumin treatment also activated G protein-coupled receptor 43 (GPR 43) in the PVN. These results indicate that curcumin reshapes the composition of the gut microbiota and ameliorates the dysregulation of the gut-brain communication to induce antihypertensive effects. [Display omitted] • Curcumin ameliorated hypertension and cardiac hypertrophy. • Curcumin altered composition of intestinal microbiota and reshaped gut microbiome. • Curcumin attenuated neuroinflammation and oxidative stress in the PVN. • Microbiota-gut-brain axis are involved in the antihypertensive effect of curcumin. [ABSTRACT FROM AUTHOR]

Abstract: Mammalian serine protease HtrA2/Omi has been known as an apoptosis inducer involved inactivation of caspase-dependent as well as caspase-independent cell death. Recent studies with the HtrA2/Omi mutant and knockout mouse models, however, suggested that HtrA2/Omi might play a protective role in neurons. It is important to establish a transgenic mouse model with neuron-specific overexpression of HtrA2/Omi to clarify the physiological function of mammalian HtrA2/Omi in neurons. In the present study, a transgene containing HtrA2/Omi cDNA downstream of a rat neuron-specific enolase promoter was constructed and microinjected into the pronuclei of fertilized zygotes to establish transgenic mice. Transgenic mice successfully overexpressed HtrA2/Omi in brain tissue. As expected, HtrA2/Omi-overexpressing transgenic mice showed normal development without any sign of apoptotic cell death. Our results suggest that the primary function of neuronal HtrA2/Omi might be to protect neurons against stress in contrast to its role in the somatic system. [Copyright &y& Elsevier]

[Display omitted] • Promoter plays a key role in gene transcription regulation. • We presented a database PPD, which collected the experimentally validated promoters in prokaryotes. • PPD recorded 129,148 promoters across 63 prokaryotic species. • PPD provided an online genome browser for the visualization of the resources of prokaryotic promoter. • PPD might be a novel resource for the study of prokaryotic gene transcription. As a key region, promoter plays a key role in transcription regulation. A eukaryotic promoter database called EPD has been constructed to store eukaryotic POL II promoters. Although there are some promoter databases for specific prokaryotic species or specific promoter type, such as RegulonDB for Escherichia coli K-12, DBTBS for Bacillus subtilis and Pro54DB for sigma 54 promoter, because of the diversity of prokaryotes and the development of sequencing technology, huge amounts of prokaryotic promoters are scattered in numerous published articles, which is inconvenient for researchers to explore the process of gene regulation in prokaryotes. In this study, we constructed a Prokaryotic Promoter Database (PPD), which records the experimentally validated promoters in prokaryotes, from published articles. Up to now, PPD has stored 129,148 promoters across 63 prokaryotic species manually extracted from published papers. We provided a friendly interface for users to browse, search, blast, visualize, submit and download data. The PPD will provide relatively comprehensive resources of prokaryotic promoter for the study of prokaryotic gene transcription. The PPD is freely available and easy accessed at http://lin-group.cn/database/ppd/. [ABSTRACT FROM AUTHOR]

The hypothalamic paraventricular nucleus (PVN) plays crucial roles in central cardiovascular regulation. Increasing evidence in humans and rodents shows that vitamin D intake is important for achieving optimal cardiovascular function. The purpose of this study was to investigate whether calcitriol, an active form of vitamin D, improves autonomic and cardiovascular function in hypertensive rats and whether PVN oxidative stress and inflammation are involved in these beneficial effects. Male spontaneously hypertensive rats (SHR) and normotensive control Wistar Kyoto (WKY) rats were treated with either calcitriol (40 ng/day) or vehicle (0.11 μL/h) through chronic PVN infusion for 4 weeks. Blood pressure and heart rate were recorded continuously by radiotelemetry. PVN tissue, heart and plasma were collected for molecular and histological analysis. Compared to WKY rats, SHR exhibited increased systolic blood pressure, sympathetic drive, and cardiac hypertrophy and remodeling. These were associated with higher mRNA and protein expression levels of high mobility box 1 (HMGB1), receptor for advanced glycation end products (RAGE), toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB), proinflammatory cytokines, NADPH oxidase subunit in the PVN. In addition, increased norepinephrine in plasma, elevated reactive oxygen species levels and activation of microglia in the PVN were also observed in SHR. Chronic calcitriol treatment ameliorated these changes but not in WKY rats. Our results demonstrate that chronic infusion of calcitriol in the PVN ameliorates hypertensive responses, sympathoexcitation and retains cardiovascular function in SHR. Reduced inflammation and oxidative stress within the PVN are involved in these calcitriol-induced effects. • PVN infusion of calcitriol ameliorates autonomic dysfunction and hypertension. • Chronic calcitriol treatmen attenuates cardiac hypertrophy and remodeling. • Chronic calcitriol treatment reduces PVN neuroinflammation and oxidative stress. • HMGB1-RAGE/TLR4-NF-κB axis in PVN is associated with the effects of calcitriol. [ABSTRACT FROM AUTHOR]

Radioresistance (inherent or acquired) remains a major obstacle affecting the clinical outcome of radiotherapy for laryngeal carcinoma. Results from our laboratory and other groups suggest that aberrant glycosylation contributes to cancer acquired radioresistance. However, the role of glycosylation in inherent radioresistance of laryngeal carcinoma has not been fully uncovered. In this study, we investigated the glycan profiling of the inherent radioresistant (Hep-2max) and radiosensitive (Hep-2 min) cell lines using lectin microarray analysis. The results revealed that the radioresistant cell line Hep-2max presented higher core 1-type O-glycans than the sensitive one. Further analysis of the O-glycan regulation by benzyl-α-GalNAc application in Hep-2max cells showed partial inhibition of the O-glycan biosynthesis and increased radiosensitivity. In addition, core 1 β1, 3-galactosyltransferase (C1GALT1) overexpression in Hep-2 min cells enhanced cell migration, invasion, and radioresistance. Conversely, knockdown of C1GALT1 in Hep-2max cells was able to suppress these malignant phenotypes. Moreover, mechanistic investigations showed that C1GALT1 modified the O-glycans on integrin β1 and regulated its activity. The glycosylation-mediated radioresistance was further inhibited by anti-integrin β1 blocking antibody. Importantly, we also observed that core 1-type O-glycans expression was correlated with advanced tumor stage, metastasis, and poor survival of laryngeal carcinoma patients. These findings suggest that altered O-glycosylation can lead to the inherent radioresistance and progression, and therefore may be important for enhancing the efficacy of radiotherapy in laryngeal carcinoma. [ABSTRACT FROM AUTHOR]

In our previous work, miR-31 displayed differential significant expression in Apostichopus japonicus sea cucumber with skin ulcer syndrome and modulated coelomocytes ROS production by targeting p105. To identify other promising targets ofmiR-31, 4 transcriptome libraries of coelomocytes, as well as 2 control libraries, were constructed frommiR-31 mimics (31 M) or AMO-miR-31 (31I) and injected into a sea cucumber at 12 and 24 h. A total of207,977 unigenes with an average length of 363 bp were assembled, in which17,204 distinct sequences (8.27% of the unigenes) were successfully matched with annotated protein sequences. Fragments per kilobase of transcript per million fragments mapped analysis indicated that 1325 unigenes displayed up-regulated expression profiles in the 31I-12 group and were depressed in the 31M − 12 group compared with the control group. A total of 1470 unigenes showed down-regulated expressions in 31I-12 and were induced in 31 M-12. Similarly, 2079 and 2098 unigenes were detected at 24 h post-injection. Among these unigenes, 36 unigenes (depressed expression in the 31 M group and induced in the 31I group) showed consistent expression patterns at 2 examined time points and were considered promising targets of miR-31. qPCR analysis confirmed that all 4 unigenes showed opposite expression profiles to miR-31 in cultured coelomocytes. Our present work provided a fast and feasible method of identifying miR-31 targets by transcriptome analysis. The results of this study would enhance our present understanding ofmiR-31 function insea cucumber immune regulation. [ABSTRACT FROM AUTHOR]