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Background and Purpose: Inhibitors of voltage-gated sodium channels (Na V s) are important anti-epileptic drugs, but the contribution of specific channel isoforms is unknown since available inhibitors are non-selective. We aimed to create novel, isoform selective inhibitors of Na v channels as a means of informing the development of improved antiseizure drugs., Experimental Approach: We created a series of compounds with diverse selectivity profiles enabling block of Na V 1.6 alone or together with Na V 1.2. These novel Na V inhibitors were evaluated for their ability to inhibit electrically evoked seizures in mice with a heterozygous gain-of-function mutation (N1768D/+) in Scn8a (encoding Na V 1.6) and in wild-type mice., Key Results: Pharmacologic inhibition of Na V 1.6 in Scn8a N1768D/+ mice prevented seizures evoked by a 6-Hz shock. Inhibitors were also effective in a direct current maximal electroshock seizure assay in wild-type mice. Na V 1.6 inhibition correlated with efficacy in both models, even without inhibition of other CNS Na V isoforms., Conclusions and Implications: Our data suggest Na V 1.6 inhibition is a driver of efficacy for Na V inhibitor anti-seizure medicines. Sparing the Na V 1.1 channels of inhibitory interneurons did not compromise efficacy. Selective Na V 1.6 inhibitors may provide targeted therapies for human Scn8a developmental and epileptic encephalopathies and improved treatments for idiopathic epilepsies., (© 2024 The Author(s). British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Simple Summary: This study investigated different feeding frequencies for white shrimp in intensive aquaculture using automatic feeders, and found that feeding 6–8 times/day resulted in higher growth, better feed conversion, improved digestive and antioxidant capacity, and higher profits compared to manual feeding. We believe that our study makes a significant contribution to the literature by demonstrating the effectiveness of automatic feeders and different feeding frequencies in white shrimp aquaculture. The findings highlight the benefits of feeding 6–8 times/day, leading to improved growth, feed utilization, and antioxidant capacity, with economic advantages for intensive shrimp culture operations. Feeding frequency is crucial for the growth and development of white shrimp (Litopenaeus vannamei) at various life stages. Although higher feeding frequencies can enhance growth, manual feeding methods significantly increase labor costs. Automatic feeding systems offer a cost-effective and efficient alternative, yet their application in intensive shrimp culture remains under-researched. This study evaluates different feeding frequencies for L. vannamei in intensive aquaculture tanks, focusing on growth performance, survivability, feed utilization, digestive and antioxidant capacities, and economic viability. Juvenile shrimp (3.85 ± 0.3 g) were cultured for 63 days with feeding frequencies of 6, 8, 10, and 12 times/day (A6, A8, A10, and A12 groups, respectively) using automatic feeders, with a control group fed manually 6 times/day (M6). Results indicated that automatic feeding significantly improved final body weight, specific growth rate, and feed conversion ratio compared to manual feeding. Among automatic feeding groups, A6 and A8 showed optimal performance, with a quadratic regression identifying 7.83 times/day as the optimal frequency. While digestive enzyme activity remained consistent across groups, A6 and A8 demonstrated significantly higher antioxidant enzyme levels (superoxide dismutase (SOD) and glutathione peroxidase (GPx)) and lower lipid peroxidation (MDA), suggesting superior digestive and antioxidant capacities. Pearson's correlation confirmed a positive relationship between SOD and GPx. Economically, the A8 group achieved the highest profitability. Consequently, a feeding frequency of 6–8 times/day using automatic feeders is recommended as an optimal and feasible strategy for intensive white shrimp culture in this life stage. [ABSTRACT FROM AUTHOR]

Combustion is the most advanced and proven method on the market for using agricultural by-product residues and waste from the agri-food industry. Currently, a wide range of combustion technologies is used to produce heat and electricity in low-power heating devices (>50 kW) using various types of biofuels from biomass (woody biomass, herbaceous biomass, waste and residues from the agri-food industry). Combustion of biomass fuels, especially those of wood origin, causes lower carbon dioxide (CO2) and sulfur oxides (SOx) emissions into the atmosphere compared to coal combustion. The growing interest in solid biofuels has contributed to intensive activities on improving the combustion process and energy devices enabling effective and economic conversion of chemical energy contained in biomass into other usable forms such as heat, electricity. Having good quality fuel, it is necessary to ensure an appropriate, clean combustion technique, which allows to achieve the highest thermal efficiency of the heating device and at the same time the lowest emission of pollutants. The article presents issues related to the theory, characteristics of the combustion process and problems related to the formation of harmful chemical compounds nitrogen oxides (NOx), SOx, carbon monoxide (CO), particulate matter (PM) emitted to the atmosphere during the combustion process in low-power heating devices. The analysis indicates the possibility of minimizing undesirable phenomena during the combustion of these biofuels related to ash sintering, the formation of deposits, corrosion and improving the amount of condensable solid particles formed and therefore reducing the emission of gaseous products to the environment. [ABSTRACT FROM AUTHOR]

Competition between bacterial species is a major factor shaping microbial communities. It is possible but remains largely unexplored that competition between bacterial pathogens can be mediated through antagonistic effects of bacterial effector proteins on host systems, particularly the actin cytoskeleton. Using Salmonella Typhimurium invasion into cells as a model, we demonstrate that invasion is inhibited if the host actin cytoskeleton is disturbed by actin-specific toxins, namely, Vibrio cholerae MARTX actin crosslinking (ACD) and Rho GTPase inactivation (RID) domains, Photorhabdus luminescens TccC3, and Salmonella's own SpvB. We noticed that ACD, being an effective inhibitor of tandem G-actin-binding assembly factors, is likely to inhibit the activity of another Vibrio effector, VopF. In reconstituted actin polymerization assays and by live-cell microscopy, we confirmed that ACD potently halted the actin nucleation and pointed-end elongation activities of VopF, revealing competition between these two V. cholerae effectors. These results suggest that bacterial effectors from different species that target the same host machinery or proteins may represent an effective but largely overlooked mechanism of indirect bacterial competition in host-associated microbial communities. Whether the proposed inhibition mechanism involves the actin cytoskeleton or other host cell compartments, such inhibition deserves investigation and may contribute to a documented scarcity of human enteric co-infections by different pathogenic bacteria. [ABSTRACT FROM AUTHOR]

Teacher training initiatives for Physically Active Learning (PAL) are notably scarce, particularly within the realm of English Language Education and within the contexts of developing countries. This research delineates a comprehensive training program specifically tailored for English as a Foreign Language (EFL) instructors in Türkiye, aiming to foster Physically Active Language Learning (PALL). The study engaged thirty in-service EFL teachers from diverse state schools in the training initiative. In this study, a mixed methods design was employed, involving the collection and integration of both qualitative and quantitative data. This approach allowed for a comprehensive examination of the changes observed in teachers' motivation for recreational exercise, playfulness, physical activity efficacy, and attitudes toward sports. Specifically, the research design included surveys to gather quantitative data and semi-structured interviews for qualitative insights. The data collection methods encompassed standardized questionnaires and in-depth interviews, which were analyzed using statistical methods and thematic analysis, respectively. These factors are crucial in influencing teachers' willingness to adopt, implement, and promote physical activity learning (PAL). The results demonstrated significant improvements in teachers' mastery motives and increased interest in sports. Additionally, the study provides valuable insights into the potential long-term impact of the training program on teaching practices and student outcomes, shedding light on the sustainability and effectiveness of integrating PALL into educational settings. Overall, teacher feedback indicated overwhelmingly positive perceptions of the PALL training program. [ABSTRACT FROM AUTHOR]

Introduction: This article provides an overview of several experimental models, including in vivo, genetics, chemical, knock-in, knock-out, electrical, in vitro, and optogenetics models, that have been employed to investigate epileptogenesis. The present review introduces a novel categorization of these models, taking into account the fact that the most recent classification that gained widespread acceptance was established by Fisher in 1989. A significant number of such models have become virtually outdated. Objective: This paper specifically examines the models that have contributed to the investigation of partial seizures, generalized seizures, and status epilepticus. Discussion: A description is provided of the primary features associated with the processes that produce and regulate the symptoms of various epileptogenesis models. Numerous experimental epilepsy models in animals have made substantial contributions to the investigation of particular brain regions that are capable of inducing seizures. Experimental models of epilepsy have also enabled the investigation of the therapeutic mechanisms of anti-epileptic medications. Typically, animals are selected for the development and study of experimental animal models of epilepsy based on the specific form of epilepsy being investigated. Conclusions: Currently, it is established that specific animal species can undergo epileptic seizures that resemble those described in humans. Nevertheless, it is crucial to acknowledge that a comprehensive assessment of all forms of human epilepsy has not been feasible. However, these experimental models, both those derived from channelopathies and others, have provided a limited comprehension of the fundamental mechanisms of this disease. [ABSTRACT FROM AUTHOR]

Although blood autoantibodies were initially associated with autoimmune diseases, multiple evidence have been accumulated showing their presence in many types of cancer. This has opened their use in clinics, since cancer autoantibodies might be useful for early detection, prognosis, and monitoring of cancer patients. In this review, we discuss the different techniques available for their discovery and validation. Additionally, we discuss here in detail those autoantibody panels verified in at least two different reports that should be more likely to be specificof eachof the four most incident cancers. We also report the recent developed kits for breast and lung cancer detectionmostly based on autoantibodies and the identification of novel therapeutic targets because of the screening of the cancer humoral immune response. Finally, we discuss unsolved issues that still need to be addressed for the implementation of cancer autoantibodies in clinical routine for cancer diagnosis, prognosis, and/or monitoring. [ABSTRACT FROM AUTHOR]

Several studies have identified a recurring trend that speech-language pathologists (S-LPs) in countries such as the United States (Caesar & Kitila, 2020), South Africa (Singh et al., 2015), and Malaysia (Kamal et al., 2012) report lower levels of confidence in dysphagia management, whether in comparison to other practice areas or in certain skill areas within the specialty of dysphagia. No data currently exists exploring self-perceptions of Canadian S-LP graduates with regards to clinical management of adults with dysphagia. Therefore, the purpose of this study was to determine the self-reported readiness of recently graduated Canadian S-LPs who manage dysphagia. Our survey was derived from a modified version of the Dysphagia Competency Verification Tool and distributed to graduates (Classes of 2018-2022) via four Canadian speech-language pathology program offices and direct emailing of graduates in select provinces. Of the 135 individuals who signed up to receive the survey, 92 eligible participants completed the survey. Median scores revealed that respondents perceived themselves to be comfortable with clinical skills related to general knowledge (i.e., educating patients), direct patient care, videofluoroscopic swallowing studies (VFSS), and basic flexible endoscopic evaluation of swallowing studies (FEES) skills. However, many graduates felt uncomfortable with select skills relating to dysphagia rehabilitation (i.e., providing a prognostic statement) and advanced FEES skills. Correlational analyses showed some associations between province of education and reported comfort levels in five of the survey items. Posthoc comparisons were made between those who graduated pre-COVID and those who graduated post-COVID, the latter group scoring higher on select VFSS skills. Results emphasize the need for further research into S-LPs' preparedness following graduation and highlight potential areas for further development in Canadian graduate programs. [ABSTRACT FROM AUTHOR]

It has been hypothesized that key lifestyle behaviors of physical activity and sleep worsened in response to the Coronavirus disease (COVID-19) pandemic. However, there have been inconsistencies in findings of changes in these key lifestyle behaviors across populations likely due to the wide variety of assessment methods. The purpose of the study was to compare physical activity and sleep before and after the COVID-19 pandemic using accelerometers and self-reported behaviors. A longitudinal follow-up was conducted on students, faculty, and staff at a university campus in the United States. In the periods before March 2020 (covering the academic years of 2018-2019 or 2019-2020) and again in April-June 2021, participants completed surveys to evaluate their physical activity and sleep behaviors and wore an accelerometer. A total of 44 participants completed the survey at both timepoints and 32 completed accelerometer assessment at both timepoints. Fifty-seven percent of participants reported a perceived decline in physical activity, while 30% reported a worsening in sleep. From self-reported data, overall physical activity did not change, but there was a decrease in active transport (p < 0.001) and increase in domestic physical activity (p = 0.012). Sleep quality decreased as evidenced by an increase in Pittsburgh Sleep Quality Index scores (p = 0.045). There were no changes in accelerometer measured physical activity or sleep. There were no changes in physical or mental health. While perceptions of physical activity declined from prior to the COVID-19 pandemic, there were no changes in device-measured physical activity, and changes in self-reported physical activity differed by domain. [ABSTRACT FROM AUTHOR]

This comprehensive review delves into the burgeoning role of gold nanoparticles in both cancer treatment and diagnostics. The advent of gold nanoparticle (AuNP) vaccines has opened avenues for therapeutic and prophylactic applications, suggesting the potential to prevent or treat infections and various pathologies. The exceptional efficacy of AuNPs in cancer treatment is a focal point of exploration, with ongoing investigations into their utility for targeted delivery and therapy across diverse cancer types. A distinctive attribute of AuNPs lies in their ability to selectively target cancerous cells while safeguarding healthy cells, attributed to their unique size and shape that facilitate selective accumulation in cancer cells. Upon cellular entry and aggregation, they exhibit prompt activation to eradicate cancer cells. Furthermore, AuNPs possess inherent capabilities to enhance and modulate immune responses, functioning as both an adjuvant and a delivery system. Another advantageous feature is their amenability to functionalization with diverse molecules, including antibodies and drugs, augmenting specificity and effectiveness. This customization enables precise targeting of cancer cells and direct delivery of therapeutic agents to tumor sites, mitigating the adverse effects associated with conventional chemotherapy. Despite ongoing research, the promise of AuNPs as a potent tool in the battle against cancer is evident, underscoring their potential significance in future therapeutic strategies. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to examine whether ACTN3 rs1815739 polymorphism, which causes the deficiency of the alpha-actinin-3 muscle protein, is related to the formation of open bite malocclusion., Materials and Methods: Fifty-eight participants (18.5 ± 3.6 years old) with anterior open bite (n = 29) and normal overbite (n = 29) who presented to Marmara University, Department of Orthodontics for treatment were included in the study. Initial cephalometric radiographs were used for the diagnosis of malocclusion. The case group was divided into three subgroups according to degree of open bite. For DNA isolation, oral epithelial cells were collected with buccal swabs (Van Allen Way, Carlsbad, USA), and the real-time PCR method was used for the genotyping of all polymorphisms. The results were statistically analysed, and the threshold for statistical significance was set at p < 0.05., Results: The frequencies of RR, RX and XX genotypes of ACTN3 rs1815739 polymorphism were found as 6 (20.7%), 14 (48.3%) and 9 (31.0%) in the control group and 8 (8%), 9 (31.0%) and 12 (41.4%) in the case group, respectively. There was no statistically significant difference between the groups in terms of the presence of the examined polymorphism (p > 0.05). However, the intra-group evaluation of case group revealed a significant difference in the prevalence of XX genotype (83.3%) for the subgroup with an open bite of -5 mm or above., Conclusion: Although no significant difference was observed between the case and control groups, a possible association was identified between ACTN3 rs1815739 polymorphism and an increased severity of open bite malocclusion., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Hereditary multiple exostoses (HME) is an autosomal dominant skeletal disorder primarily linked with mutations in Exostosin-1 (EXT1) and Exostosin-2 (EXT2) genes. However, not all HME cases can be explained by these mutations, and its pathogenic mechanisms are not fully understood. Herein, utilizing whole-exome sequencing and genetic screening with a family trio design, we identify two novel rare mutations co-segregating with HME in a Chinese family, including a nonsense mutation (c.204G>A, p.Trp68*) in EXT1 and a missense mutation (c.893T>G, p.Phe298Cys) in FUT7. Functional assays reveal that the FUT7 mutation affects the cellular localization of FUT7 protein and regulates cell proliferation. Notably, the simultaneous loss of fut7 and ext1 in a zebrafish model results in severe chondrodysplasia, indicating a functional link between FUT7 and EXT1 in chondrocyte regulation. Additionally, we unveil that FUT7 p.Phe298Cys reduces EXT1 expression through IL6/STAT3/SLUG axis at the transcription level and through ubiquitination-related proteasomal degradation at the protein level. Together, our findings not only identify novel germline mutations in FUT7 and EXT1 genes, but also highlight the critical interaction between these genes, suggesting a potential 'second-hit' mechanism over EXT1 mutations in HME pathogenesis. This insight enhances our understanding of the mechanisms underlying HME and opens new avenues for potential therapeutic interventions., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: All methods used in the present study were in accordance with the relevant guidelines and regulations. This study was approved by the Ethics Committee for Clinical Research and Animal Trials of the First Affiliated Hospital of Sun Yat-sen University (permit NO. [2020]363). Informed consent was obtained from all the participants. All work involving zebrafish was reviewed and approved by the Animal Research Advisory Committee of the South China University of Technology., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Arboviruses are a diverse group of insect-transmitted pathogens that pose global public health challenges. Identifying evolutionarily conserved host factors that combat arbovirus replication in disparate eukaryotic hosts is important as they may tip the balance between productive and abortive viral replication, and thus determine virus host range. Here, we exploit naturally abortive arbovirus infections that we identified in lepidopteran cells and use bacterial effector proteins to uncover host factors restricting arbovirus replication. Bacterial effectors are proteins secreted by pathogenic bacteria into eukaryotic hosts cells that can inhibit antimicrobial defenses. Since bacteria and viruses can encounter common host defenses, we hypothesized that some bacterial effectors may inhibit host factors that restrict arbovirus replication in lepidopteran cells. Thus, we used bacterial effectors as molecular tools to identify host factors that restrict four distinct arboviruses in lepidopteran cells. By screening 210 effectors encoded by seven different bacterial pathogens, we identify several effectors that individually rescue the replication of all four arboviruses. We show that these effectors encode diverse enzymatic activities that are required to break arbovirus restriction. We further characterize Shigella flexneri-encoded IpaH4 as an E3 ubiquitin ligase that directly ubiquitinates two evolutionarily conserved proteins, SHOC2 and PSMC1, promoting their degradation in insect and human cells. We show that depletion of either SHOC2 or PSMC1 in insect or human cells promotes arbovirus replication, indicating that these are ancient virus restriction factors conserved across invertebrate and vertebrate hosts. Collectively, our study reveals a novel pathogen-guided approach to identify conserved antimicrobial machinery, new effector functions, and conserved roles for SHOC2 and PSMC1 in virus restriction. Author summary: Microbial pathogens such as viruses and bacteria encounter diverse host cell responses during infection. While viruses possess antagonists to counter these responses in natural host species, their replication can be restricted in unnatural host cells where their antagonists are ineffective. Bacteria also employ a diverse repertoire of immune evasion proteins known as "effectors" that can inhibit antimicrobial responses found in invertebrate and vertebrate hosts. In this study, we hypothesized that some bacterial effectors may target host immunity proteins that restrict both bacteria and viruses. To test this hypothesis, we screened a bacterial effector library comprising 210 effectors from seven distinct bacterial pathogens for their ability to rescue the replication of four viruses in insect cells that are normally non-permissive to these viruses. Though numerous effectors were identified to rescue the replication of each virus, the uncharacterized IpaH4 protein encoded by the human pathogen Shigella flexneri was able to rescue all four viruses screened. We discovered that IpaH4 enhances arbovirus replication in both restrictive insect and permissive human cells by directly targeting two novel, evolutionarily conserved antiviral host proteins, SHOC2 and PSMC1, for degradation. Our study establishes bacterial effectors as valuable tools for identifying critical antimicrobial machinery employed by eukaryotic hosts. [ABSTRACT FROM AUTHOR]

Salmonella enterica is a leading cause of bacterial food-borne illness in humans and is responsible for millions of cases annually. A critical strategy for the survival of this pathogen is the translocation of bacterial virulence factors termed effectors into host cells, which primarily function via protein–protein interactions with host proteins. The Salmonella genome encodes several paralogous effectors believed to have arisen from duplication events throughout the course of evolution. These paralogs can share structural similarities and enzymatic activities but have also demonstrated divergence in host cell targets or interaction partners and contributions to the intracellular lifecycle of Salmonella. The paralog effectors SopD and SopD2 share 63% amino acid sequence similarity and extensive structural homology yet have demonstrated divergence in secretion kinetics, intracellular localization, host targets, and roles in infection. SopD and SopD2 target host Rab GTPases, which represent critical regulators of intracellular trafficking that mediate diverse cellular functions. While SopD and SopD2 both manipulate Rab function, these paralogs display differences in Rab specificity, and the effectors have also evolved multiple mechanisms of action for GTPase manipulation. Here, we highlight this intriguing pair of paralog effectors in the context of host–pathogen interactions and discuss how this research has presented valuable insights into effector evolution. [ABSTRACT FROM AUTHOR]

Purpose: Previous studies have suggested that many speech-language pathology graduate students experience significant levels of stress throughout their programs. If not effectively mitigated, these stressors could negatively impact students' academic and clinical development. Self-care practices are one potential option that could help address the stressors students encounter throughout their graduate programs. The purpose of this research was to explore potential associations between self-care practices and clinical selfefficacy in speech-language pathology graduate students. Method: This topic was explored using a nonexperimental research design that included descriptive and correlational analyses. A survey that included demographic questions, the Mindful Self-Care Scale--Standard, and a modified version of the Clinical Self-Efficacy Appraisal Inventory was completed by 68 students who were enrolled in a speech-language pathology graduate program. Results: Small positive and significant correlational associations were observed between Mindful Awareness and total Mindful Self-Care Scale--Standard scores and all measured aspects of clinical self-efficacy. The associations between Supportive Relationships and Supportive Structure subscale scores and some aspects of clinical self-efficacy also reached significance. No significant associations were observed between Mindful Relaxation, Physical Care, or Self-Compassion and Purpose subscale scores and any measured domain of clinical self-efficacy. Conclusion: While limitations exist due to the exploratory nature of this study, the results provide an initial examination of associations between self-care practices and clinical self-efficacy. [ABSTRACT FROM AUTHOR]

Background: Quantifying movement behaviours over 24-hours enables the combined effects of and inter-relations between sleep, sedentary time and physical activity (PA) to be understood. This is the first study describing 24-hour movement behaviours in school-aged children and adolescents in South-East Asia. Further aims were to investigate between-participant differences in movement behaviours by demographic characteristics and timing of data collection during Ramadan and COVID-19 restrictions. Methods: Data came from the South-East Asia Community Observatory health surveillance cohort, 2021–2022. Children aged 7–18 years within selected households in Segamat, Malaysia wore an Axivity AX6 accelerometer on their wrist for 24 hours/day over 7 days, completed the PAQ-C questionnaire, and demographic information was obtained. Accelerometer data was processed using GGIR to determine time spent asleep, inactive, in light-intensity PA (LPA) and moderate-to-vigorous PA (MVPA). Differences in accelerometer-measured PA by demographic characteristics (sex, age, ethnicity, socioeconomic group) were explored using univariate linear regression. Differences between data collected during vs outside Ramadan or during vs after COVID-19 restrictions, were investigated through univariate and multiple linear regressions, adjusted for age, sex and ethnicity. Results: The 491 participants providing accelerometer data spent 8.2 (95% confidence interval (CI) = 7.9–8.4) hours/day asleep, 12.4 (95% CI = 12.2–12.7) hours/day inactive, 2.8 (95% CI = 2.7–2.9) hours/day in LPA, and 33.0 (95% CI = 31.0–35.1) minutes/day in MVPA. Greater PA and less time inactive were observed in boys vs girls, children vs adolescents, Indian and Chinese vs Malay children and higher income vs lower income households. Data collection during Ramadan or during COVID-19 restrictions were not associated with MVPA engagement after adjustment for demographic characteristics. Conclusions: Demographic characteristics remained the strongest correlates of accelerometer-measured 24-hour movement behaviours in Malaysian children and adolescents. Future studies should seek to understand why predominantly girls, adolescents and children from Malay ethnicities have particularly low movement behaviours within Malaysia. [ABSTRACT FROM AUTHOR]

Purpose: Guanfacine is an α2A-adrenergic receptor agonist, FDA-approved to treat attention-deficit hyperactivity disorder and high blood pressure, typically as an extended-release formulation up to 7 mg/day. In our dysautonomia clinic, we observed that off-label use of short-acting guanfacine at 1 mg/day facilitated symptom relief in two families with multiple members presenting with severe generalized anxiety. We also noted anecdotal improvements in associated dysautonomia symptoms such as hyperhidrosis, cognitive impairment, and palpitations. We postulated that a genetic deficit existed in these patients that might augment guanfacine susceptibility. Methods: We used whole-exome sequencing to identify mutations in patients with shared generalized anxiety and dysautonomia symptoms. Guanfacine-induced changes in the function of voltage-gated Na+ channels were investigated using voltage-clamp electrophysiology. Results: Whole-exome sequencing uncovered the p.I739V mutation in SCN9A in the proband of two nonrelated families. Moreover, guanfacine inhibited ionic currents evoked by wild-type and mutant NaV1.7 encoded by SCN9A, as well as other NaV channel subtypes to a varying degree. Conclusion: Our study provides further evidence for a possible pathophysiological role of NaV1.7 in anxiety and dysautonomia. Combined with off-target effects on NaV channel function, daily administration of 1 mg short-acting guanfacine may be sufficient to normalize NaV channel mutation-induced changes in sympathetic activity, perhaps aided by partial inhibition of NaV1.7 or other channel subtypes. In a broader context, expanding genetic and functional data about ion channel aberrations may enable the prospect of stratifying patients in which mutation-induced increased sympathetic tone normalization by guanfacine can support treatment strategies for anxiety and dysautonomia symptoms. [ABSTRACT FROM AUTHOR]

Wetlands process large amounts of carbon (C) that can be exported laterally to streams and rivers. However, our understanding of wetland inputs to streams remains unclear, particularly in tropical systems. Here we estimated the contribution of seasonal wetlands to the C pool of a lowland headwater stream in the Australian tropics. We measured dissolved organic and inorganic C (DOC and DIC) and dissolved gases (carbon dioxide—CO2, methane—CH4) during the wet season along the mainstem and in wetland drains connected to the stream. We also recorded hourly measurements of dissolved CO2 along a 'stream–wetland drain–stream' continuum, and used a hydrological model combined with a simple mass balance approach to assess the water, DIC and DOC sources to the stream. Seasonal wetlands contributed ∼15% and ∼16% of the DOC and DIC loads during our synoptic sampling, slightly higher than the percent area (∼9%) they occupy in the catchment. The riparian forest (75% of the DOC load) and groundwater inflows (58% of the DIC load) were identified as the main sources of stream DOC and DIC. Seasonal wetlands also contributed marginally to stream CO2 and CH4. Importantly, the rates of stream CO2 emission (1.86 g C s−1) and DOC mineralization (0.33 g C s−1) were much lower than the downstream export of DIC (6.39 g C s−1) and DOC (2.66 g g C s−1). This work highlights the need for further research on the role of riparian corridors as producers and conduits of terrestrial C to tropical streams. Plain Language Summary: Streams and rivers play a vital role in carrying carbon to oceans. This carbon can originate from biological processes in the water or from external sources like rocks, forest and wetland soils. The proportion of carbon from each source depends on factors such as the local geology, climate, and landscape. In this study, we measured how much of the carbon transported by an Australian tropical stream was sourced from the wetlands in the catchment. We found that seasonal wetlands contributed ∼15% of the carbon measured in the stream. We conclude that the main sources of carbon to the stream were the riparian forest, and rock‐derived carbon carried by groundwater. Key Points: Synoptic sampling of DIC, DOC and dissolved C gases along a tropical stream and connected wetlandsSeasonal wetlands contributed ∼15% and 16% of the stream DOC and DIC loadsThe riparian forest and groundwater inflows were likely the main sources of DOC and DIC to the stream, respectively [ABSTRACT FROM AUTHOR]

Glioma represents the most common primary cancer of the central nervous system in adults. Glycosylation is a prevalent post-translational modification that occurs in eukaryotic cells, leading to a wide array of modifications on proteins. We obtained the clinical information, bulk RNA-seq data, and single-cell RNA sequencing (scRNA-seq) from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), Gene Expression Omnibus (GEO), and Repository of Molecular Brain Neoplasia Data (Rembrandt) databases. RNA sequencing data for normal brain tissues were accessed from the Genotype- Tissue Expression (GTEx) database. Then, the glycosylation genes that were differentially expressed were identified and further subjected to variable selection using a least absolute shrinkage and selection operator (LASSO)- regularized Cox model. We further conducted enrichment analysis, qPCR, nomogram, and single-cell transcriptome to detect the glycosylation signature. Drug sensitivity analysis was also conducted. A five-gene glycosylation signature (CHPF2, PYGL, GALNT13, EXT2, and COLGALT2) classified patients into low- or high-risk groups. Survival analysis, qPCR, ROC curves, and stratified analysis revealed worse outcomes in the high-risk group. Furthermore, GSEA and immune infiltration analysis indicated that the glycosylation signature has the potential to predict the immune response in glioma. In addition, four drugs (crizotinib, lapatinib, nilotinib, and topotecan) showed different responses between the two risk groups. Glioma cells had been classified into seven lines based on single-cell expression profiles. The five-gene glycosylation signature can accurately predict the prognosis of glioma and may offer additional guidance for immunotherapy. [ABSTRACT FROM AUTHOR]

Research shows that exposure to high environmental temperatures can affect task performance. Theoretical explanations outline that heat is a source of stress that competes for limited-capacity resources, therefore if a task is resource-intensive, and/or if heat stress is extreme, performance will suffer. One occupation in which individuals complete demanding tasks and make difficult decisions, often in temperatures exceeding 200°C, is firefighting. Yet very little is currently known about the impact of heat stress on the cognitive functioning of firefighters. This short review summarizes the limited research in this area, focusing on studies that measured cognition of firefighters following a realistic training exercise. The findings are mixed with evidence that heat stress improves, impairs, and has no impact on cognitive functioning. While there are differences in the firefighting activities utilized, and the temperatures that participants were exposed to, it is argued that the varied findings can be attributed to the tasks used to assess cognitive processing, and the cognitive functions being measured. In accordance with the wider field of research, it is concluded that complex functioning, such as sustained attention, vigilance, and working memory is negatively impacted by acute exposure to extreme heat. Greater understanding of factors affecting cognition would inform safety practices and more research is needed to understand how and when heat stress may influence cognition in firefighting scenarios. [ABSTRACT FROM AUTHOR]

Objective: To assess the overall effectiveness of non-pharmacological interventions on internet addiction (IA) in youth. Method: Randomized controlled trials (RCTs) published from their inception to April 1, 2023 were searched in Cochrane, Embase, Medline, Web of Science, China National Knowledge Infrastructure, China Science and Technology Journal Database, Chinese BioMedical Literature Database, and WanFang Data. Two reviewers independently extracted data and evaluated bias using the Cochrane Risk of Bias tool. Results: Sixty-six studies performed from 2007 to 2023, with a total of 4,385 participants, were identified. The NPIs included group counseling, cognitive behavioral therapy, sports intervention, combined interventions, eHealth, educational intervention, positive psychology intervention, sand play intervention, and electrotherapy. The results revealed that NPIs significantly reduced IA levels (standardized mean difference, SMD: -2.01, 95% confidence interval, CI: -2.29 to -1.73, I² = 93.0%), anxiety levels (SMD: -1.07, 95%CI: -1.41 to -0.73, I² = 72.4%), depression levels (SMD: -1.11, 95%CI: -1.52 to -0.7, I² = 84.3%), and SCL-90 (SMD: -0.75, 95%CI: -0.97 to -0.54, I² = 27.7%). Subgroup analysis stratified by intervention measure showed that cognitive behavioral therapy, group counseling, sports intervention, combined intervention, educational intervention, positive psychology intervention, sandplay intervention, and mobile health were all effective in relieving symptoms of IA except electrotherapy. Conclusion: NPIs appear to be effective in the treatment of IA in youth, which would act as an alternative treatment of IA. Further studies with larger sample sizes and robust designs are needed. [ABSTRACT FROM AUTHOR]

Glycosylation is a ubiquitous cellular or microenvironment-specific post-translational modification that occurs on the surface of normal cells and tumor cells. Tumor cell-associated glycosylation is involved in hematogenous metastasis. A wide variety of tumors undergo aberrant glycosylation to interact with platelets. As platelets have many opportunities to engage circulating tumor cells, they represent an important avenue into understanding the role glycosylation plays in tumor metastasis. Platelet involvement in tumor metastasis is evidenced by observations that platelets protect tumor cells from damaging shear forces and immune system attack, aid metastasis through the endothelium at specific sites, and facilitate tumor survival and colonization. During platelet-tumor-cell interactions, many opportunities for glycan- ligand binding emerge. This review integrates the latest information about glycans, their ligands, and how they mediate platelet-tumor interactions. We also discuss adaptive changes that tumors undergo upon glycan-lectin binding and the impact glycans have on targeted therapeutic strategies for treating tumors in clinical settings. [ABSTRACT FROM AUTHOR]

Despite proven effectiveness in reducing motorist crashes involving wildlife, systematic inclusion of wildlife-mitigation measures during highway planning and projects continues to vary by jurisdiction in the United States and Canada. Some agencies invest significant resources to reduce wildlife–vehicle collisions (WVCs), while others invest few or no resources. Various factors have been identified as relevant in explaining why some jurisdictions are more proactive than others in addressing WVCs. This analysis builds on existing literature by comparing select legal decisions in the United States and Canada regarding public authority liability for failures to remediate known WVC hot spots, with the goal of assessing the potential role of liability in creating incentives for government decision makers to systematically address motorist crashes involving animals. [ABSTRACT FROM AUTHOR]

GALNT7 is a glycosyltransferase enzyme transferring N-acetylgalactosamine to initiate O-linked glycosylation in the Golgi apparatus. Breast cancer is the most common cancer in women globally. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2; ERBB2) are important biomarkers in the prognosis and molecular subtyping of breast cancer. Here, we showed that ER-positive, PR-positive or HER2-positive breast tumors have higher expression of GALNT7 compared to ER-negative, PR-negative or HER2-negative breast tumors, respectively. We found that CpG-aggregated methylation of GALNT7 gene is decreased, and in parallel, its transcript levels are increased in breast cancer compared to healthy breast tissue. We observed that the difference in the expression of GALNT7 between negative and positive status of the receptors is the highest for HER2, followed by ER and PR, pointing that HER2 might be relatively more influential than ER and PR on the expression of GALNT7 in breast cancer. We reported that basal-like breast tumors have decreased expression of GALNT7 compared to non-basal-like tumors, and that high GALNT7 expression is associated with favorable relapse-free and distant metastasis-free survival in HER2 status-dependent manner in breast cancer patients. Moreover, we showed that GALNT7 expression in breast cancer is cell type- (epithelial vs stromal cells), tumor grade- and ethnicity-dependent. Combined, we propose that GALNT7 might contribute to different clinical outcomes depending on the receptor status in breast cancer, and that a better understanding of GALNT7 and its function in the context of breast cancer is needed. [ABSTRACT FROM AUTHOR]

Carbon dioxide (CO2) is one of the main factors contributing to the greenhouse effect. The dependence on fossil fuels has led to increasing levels of carbon dioxide in the atmosphere every year. And it is far from enough to solve the climate problem by reducing the consumption of fossil fuels to cut down carbon dioxide emissions. In recent years, a series of researches on Carbon Capture, Utilization and Storage (CCUS) have been carried out in various countries around the world. CO2 is a nontoxic, tasteless and stable gas at normal temperature. However, when it reaches supercritical state after rising temperature and pressure, it has the characteristics of low viscosity, high diffusivity and high density, and is widely used in green, pollution-free and efficient development technology. Because of these unique properties, supercritical carbon dioxide (sCO2) has attracted more and more attention from researchers. sCO2 has been widely used in many aspects by virtue of its high solubility and easy compression. Different from previous reviews which only introduced the application of sCO2 property, this paper introduces the current research status of the application of the thermodynamic property of carbon dioxide in extraction, dyeing, pharmaceutical, power generation, heat transfer and exploitation of unconventional oil and gas, and mainly analyzes each application in detail from the aspects of working mechanism and improving working efficiency. Finally, the research direction and problems needed to be solved for the application of CO2 thermal physics are proposed, which pave the way for other new applications. [ABSTRACT FROM AUTHOR]

Sport, physical activity and social cohesion are increasingly linked within the academic literature. Indeed, studies recognise both the importance of social cohesion for promoting physical activity and the potential of sport to support social cohesion. Up until now, however, the ways in which social cohesion has been defined and measured in the context of sport and physical activity have not been the subject of much academic attention. Through a scoping review of studies measuring social cohesion in the sport and physical activity context, we aim to uncover how social cohesion is defined and measured, thus allowing us to better grasp how the concept is understood and operationalised in this field. As such, full-text inclusion occurred when studies quantitatively measured social cohesion through a questionnaire/survey instrument in connection with sport or physical activity participation or within programmes using sport to foster social cohesion. A total of 40 papers were included in the review, showing broad support for the argument that social cohesion is positively related to sport or physical activity participation. However, the retained texts engage on only a surface level with the concept of social cohesion, with around half not defining the term and the associated measurement tools using only a fraction of the dimensions typically associated with social cohesion. To conclude, we propose future directions to enhance conceptual engagement with and measurement of social cohesion. [ABSTRACT FROM AUTHOR]

The permeability of blood vessels plays a crucial role in the spread of cancer cells, facilitating their metastasis at distant sites. Small extracellular vesicles (sEVs) are known to contribute to the metastasis of various cancers by crossing the blood vessel wall. However, the role of abnormal glycoconjugates on sEVs in tumor blood vessels remains unclear. Our study found elevated levels of fucosyltransferase VII (FUT7) and its product sialyl Lewis X (sLeX) in muscle-invasive bladder cancer (BLCA), with high levels of sLeX promoting the growth and invasion of BLCA cells. Further investigation revealed that sLeX was enriched in sEVs derived from BLCA. sLeX-decorated sEVs increased blood vessel permeability by disrupting the tight junctions of human umbilical vein endothelial cells (HUVECs). Using the glycoproteomics approach, we identified integrin α3 (ITGA3) as a sLeX-bearing glycoprotein in BLCA cells and their sEVs. Mechanically, sLeX modification stabilized ITGA3 by preventing its degradation in lysosomes. sEVs carrying sLeX-modified ITGA3 can be effectively internalized by HUVECs, leading to a decrease in the expression of tight junction protein. Conversely, silencing ITGA3 in sLeX-decorated sEVs restored tight junction proteins and reduced blood vessel permeability by inhibiting the MAPK pathway. Moreover, sLeX-modification of ITGA3 at Asn 265 in HUVECs promoted occludin dephosphorylation at Ser/Thr residues, followed by inducing its importin α1-mediated nuclear translocation, which resulted in the disruption of tight junctions. Our findings suggest a potential strategy for disrupting the formation of a metastatic microenvironment and preventing the spread of malignant bladder cancer., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethical approval With the approval of the Ethics Committee of Northwest University, we obtained human plasma from bladder cancer patients and healthy volunteers in the First Affiliated Hospital of Xi’an Jiaotong University and the Shaanxi Provincial People's Hospital. All animal experiments are approved by the Institutional Animal Care and Use Committee of Northwest University., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background and Objectives: Schools play a crucial role in facilitating physical activity among children, but the COVID-19 pandemic has affected both children's physical activity and the school environment. It is essential to understand between-school differences in children's physical activity post lockdown, to determine if and how the role of schools has changed., Design and Participants: Active-6 is a natural experiment comparing postlockdown accelerometer-estimated physical activity to a pre-COVID-19 comparator group. Accelerometer and individual data were collected on 1296 children aged 10-11 pre-COVID-19 (2017-8), with school characteristics collected from the 50 schools they attended. Post lockdown, we collected accelerometer, individual and school data from 393 children in 23 of the same schools and 436 children in 27 of the same schools in 2021 (Wave 1) and 2022 (Wave 2), respectively., Methods: Sources of variation (between-school, between-pupil and within-pupil) in child weekday moderate to vigorous physical activity at each wave were modelled using linear mixed-effects models with school-level wave random coefficients. We extended the model to estimate the proportion of between-school variation explained by school policy, curriculum and physical environment factors and school-aggregated pupil characteristics. We also explored the extent to which postlockdown differences in moderate to vigorous physical activity were mediated by individual or school factors., Results: Between-school variation comprised 13% of the total variation pre-COVID-19, 7% in Wave 1 and 13% in Wave 2. School factors associated with moderate to vigorous physical activity were the following: whether physical education was compromised due to space (often: 9 minutes lower moderate to vigorous physical activity; sometimes: 5.4 minutes lower); high after-school club attendance (7 minutes higher moderate to vigorous physical activity for each additional club attended on average in the school); cycle training policy (4 minutes higher moderate to vigorous physical activity); and higher prevalence of active travel (1 minute higher moderate to vigorous physical activity for each 10% point increase in prevalence). These factors explained 22% of the between-school variation pre-COVID-19, and 72% at Wave 2. The relative importance changed, with cycle training policy and active travel being the most important pre-COVID-19 and cycle training policy, active after-school clubs and compromised physical education space most important in Wave 2. No factors were found to mediate the postlockdown differences in moderate to vigorous physical activity, except compromised physical education space, which had a suppressor effect in Wave 2., Limitations: Only 27 of the initial 50 schools participated post lockdown, limiting our ability to make comparisons across waves. Sample sizes were additionally affected by missing data for some variables., Conclusions and Future Work: While schools continue to play an important role in facilitating children's physical activity, the factors that contribute to this have changed post-COVID-19, with cycle training, active after-school clubs and ensuring physical education is prioritised even when space is limited now explaining nearly three-quarters of the between-school variation in children's moderate to vigorous physical activity. School-level interventions that focus on these areas, and policies that support them, may offer the potential to increase children's physical activity., Funding: This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme as award number NIHR131847.

Objectives: We report the effect of quality of therapy delivery on outcomes in a randomized, controlled trial of behavioural activation (BA) and guided self-help (GSH) for depression in adults with intellectual disabilities., Methods: A study specific measure of quality was used in a linear mixed effect model to determine the effects therapy and therapy quality on therapy outcome., Results: There was a significant interaction between quality and treatment type, with lower quality therapy associated with better outcome for GSH but poorer outcome for BA, with little difference in outcomes at higher levels of therapy quality., Conclusions: Factors suggesting high quality in individualized BA may indicate problematic engagement for GSH. More research into processes in therapy for people with intellectual disabilities is required., (© 2024 The Author(s). British Journal of Clinical Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.)

Physical activity is important for children's health, but moderate to vigorous physical activity (MVPA) declines with age. COVID-19 lockdowns resulted in reduced MVPA and increased sedentary time among children. Characterising children's activity patterns may help identify groups who are most likely to be inactive post-lockdown. Data were combined from a pre-COVID-19 cohort study on children aged 5–6 years (Year1: n = 1299), 8–9 years (Year4: n = 1223) and 10–11 years (Year6: n = 1296) and cross-sectional post-lockdown data from a natural experiment on 10-11-year-olds in 2021 (Year6-W1: n = 393) and 2022 (Year6-W2: n = 436). The proportions of time spent in MVPA, light physical activity (LPA) and sedentary time on weekdays and weekends were derived from accelerometer data. Latent class analysis was used to identify activity profiles pre and post-lockdown, and estimate pre-COVID-19 transitions between Year4 and Year6. We identified six pre-COVID-19 activity profiles in Year6, including a new profile characterised by very low MVPA and high sedentary time (19% of children). There was substantial movement between profiles at Year4 and Year6, with 45% moving to a profile with lower MVPA. Likelihood ratio tests suggested differences in Year6 activity profiles pre and post-lockdown, with a new post-lockdown profile emerging characterised by higher LPA. The percentage of children in the least active profiles (where under 20% meet UK physical activity guidelines), rose post-lockdown, from 34% pre-COVID-19 to 50% in 2021 and 40% in 2022. We also saw gender and socioeconomic gaps widen, and increased separation between high and low physical activity levels. Children's physical activity has changed post-COVID-19, in terms of who is being active and how. The impact varies by activity profile, which is influenced by gender and socio-economic position. A greater understanding of these differences and targeting of low active groups is needed to increase both individual and population levels of physical activity. [ABSTRACT FROM AUTHOR]

Prostate cancer is the most common cancer in men and a major cause of cancer related deaths worldwide. Nearly all affected men develop resistance to current therapies and there is an urgent need to develop new treatments for advanced disease. Aberrant glycosylation is a common feature of cancer cells implicated in all of the hallmarks of cancer. A major driver of aberrant glycosylation in cancer is the altered expression of glycosylation enzymes. Here, we show that GCNT1, an enzyme that plays an essential role in the formation of core 2 branched O-glycans and is crucial to the final definition of O-glycan structure, is upregulated in aggressive prostate cancer. Using in vitro and in vivo models, we show GCNT1 promotes the growth of prostate tumours and can modify the glycome of prostate cancer cells, including upregulation of core 2 O-glycans and modifying the O-glycosylation of secreted glycoproteins. Furthermore, using RNA sequencing, we find upregulation of GCNT1 in prostate cancer cells can alter oncogenic gene expression pathways important in tumour growth and metastasis. Our study highlights the important role of aberrant O-glycosylation in prostate cancer progression and provides novel insights regarding the mechanisms involved. [ABSTRACT FROM AUTHOR]

Recess is an integral part of a comprehensive school physical activity program. Immediately prior to the pandemic, state legislation doubled the amount of required recess, creating an opportunity to better understand how policies and practices influence recess. To describe changes to recess due to COVID-19 and extended recess legislation and to quantify student physical activity during recess following these changes. This mixed-method study was conducted in Spring 2021 in four elementary schools. Recess physical activity was measured using waist-worn accelerometers, recess was observed, and researchers conducted interviews with teachers and principals. Females spent 41.7% (95%CI: 38.2, 44.5) and males spent 47.9% (95%CI: 44.6, 51.2) of recess in accelerometer-measured moderate-to-vigorous physical activity (n = 164). Participants (n = 13) discussed increased supervision, classroom separation on the playground, and benefits of extended recess. States should consider extending recess requirements but need to consider options for scheduling and indoor recess. Recess continues to be a key physical activity opportunity during school. Health Educators considering changes to recess policies and practices may want to consider scheduling of recess including class integration, options for indoor recess, and professional development for recess supervision to help maximize the benefits of recess. [ABSTRACT FROM AUTHOR]

Estrous cycles are recurring changes in therian mammals induced by estrogen, progesterone, and other hormones culminating in endometrial proliferation, ovulation, and implantation if fertilization occurred. In women, the estrous cycle is the menstrual cycle; but, unlike most mammals, the end of an infertile cycle is marked by endometrial sloughing and the start of another without an anestrous phase. Women stop cycling at menopause, while in most mammals, cycles continue until death. Epidemiologic studies identified menarche, menopause, births, lactation, and oral contraceptive (OC) use as key risk factors for ovarian, breast, and endometrial cancers. A composite variable was created to estimate the number of cycles not interrupted by events that stop ovulation. Captured by the phrase "incessant ovulation", repetitive cycles were first postulated to affect ovarian cancer risk and later extended to breast and endometrial cancers. These associations could be explained by cumulative effects of repetitive tissue changes within reproductive organs, immune consequences of repetitive ovulation through the glycoprotein mucin 1, and residual effects of past ovulations that enhance ovarian production of testosterone. The latter two pathways could affect the risk for cancers in other organs not considered "reproductive". [ABSTRACT FROM AUTHOR]

The dynamics of physico-chemical, nutrient, and chlorophyll-a variables were studied in the bloom and non-bloom locations along the off-Gujarat coastal waters to understand the variability in biogeochemistry using multivariate analytical tests. The dissolved oxygen was significantly lower in the bloom stations (3.89 ± 0.44 mgL−1) than in the non-bloom stations (5.50 ± 0.70 mg L−1), due to the biological degradation of organic matter in addition to anaerobic microbial respiration. Nutrients (PO4 and NO3) and Chl-a concentrations were recorded higher in the bloom locations at 0.83 ± 0.21 µmol L−1, 4.47 ± 0.69 µmol L−1, 4.14 ± 1.49 mg m−3, respectively. PO4 and NO3 have shown a significantly higher positive correlation of r = 0.73 and r = 0.69 with Chl-a for bloom data than the non-bloom data. The percentage variance contributed by PC1 and PC2 for both bloom and non-bloom locations were estimated at 52.33%. The variable PO4 explains the highest 24.19% variability in PC1, followed by Chl-a (19.89%). The PO4 triggers the bloom formation and also correlates to the higher concentrations of Chl-a in the bloom locations. The bloom concentration ranges from 9553 to 12,235 trichomes L−1. The bloom intensity has shown a significant positive correlation with Chl-a (r = 0.77), NO3 (r = 0.56), and PO4 (r = 0.30), but a negative correlation was noticed with DO (r = − 0.63) and pH (r = − 0.49). The study also initiates a way forward research investigation on ocean-color technologies to identify and monitor blooms and climate change–driven factors for bloom formation. The occurrence of bloom and its influence on fishery resources and other marine biotas will open many research windows in marine fisheries, oceanography, remote sensing, marine biology, and trophodynamics. [ABSTRACT FROM AUTHOR]

Simple Summary: To combat infections, hosts employ a combination of antagonistic and cooperative host defense strategies. The former refers to pathogen killing mediated by host immunity (disease resistance), while the latter refers to physiological defense mechanisms that promote host health during infection independent of pathogen killing, leading to a cooperation between the host and the pathogen (diseases tolerance). In chickens, the paratyphoid Salmonella evolved the capacity to survive the initial robust immune response and persist in the avian ceca for months without triggering clinical signs. The persistent or carrier phase of a Salmonella infection in the avian host involves a complex balance of antagonistic and cooperative host defense strategies. Initially, the host reacts with a normal inflammatory response that controls bacterial invasion. After 3–4 days of inflammation, the host response changes to a more anti-inflammatory response characterized by changes in the local intestinal physiology that is no longer antagonistic to the bacterial pathogen, but instead 'tolerates' its presence. Thus, the chicken becomes a carrier of the pathogen allowing it to survive in the intestine without causing disease. It is hoped that understanding these mechanisms of pathogen survival in the chicken will allow future research to exploit these novel disease tolerance mechanisms to impact poultry health and reduced foodborne infections of Salmonella. The gastrointestinal ecosystem involves interactions between the host, gut microbiota, and external environment. To colonize the gut of poultry, Salmonella must surmount barriers levied by the intestine including mucosal innate immune responses and microbiota-mediated niche restrictions. Accordingly, comprehending Salmonella intestinal colonization in poultry requires an understanding of how the pathogen interacts with the intestinal ecosystem. In chickens, the paratyphoid Salmonella have evolved the capacity to survive the initial immune response and persist in the avian ceca for months without triggering clinical signs. The persistence of a Salmonella infection in the avian host involves both host defenses and tolerogenic defense strategies. The initial phase of the Salmonella–gut ecosystem interaction is characteristically an innate pro-inflammatory response that controls bacterial invasion. The second phase is initiated by an expansion of the T regulatory cell population in the cecum of Salmonella-infected chickens accompanied by well-defined shifts in the enteric neuro-immunometabolic pathways that changes the local phenotype from pro-inflammatory to an anti-inflammatory environment. Thus, paratyphoid Salmonella in chickens have evolved a unique survival strategy that minimizes the inflammatory response (disease resistance) during the initial infection and then induces an immunometabolic reprogramming in the cecum that alters the host defense to disease tolerance that provides an environment conducive to drive asymptomatic carriage of the bacterial pathogen. [ABSTRACT FROM AUTHOR]

Background: Various interventions, programs and policies have been implemented to improve physical activity (PA) levels worldwide. However, countries continue to face barriers and challenges in achieving their targets. To date, there is a lack of study on the evaluation of physical activity (PA) promotion and how it's associated with public participation. Methods: This study assessed PA promotion in eight different settings in terms of policy availability, policy implementation, and public participation in PA programs. Policy availability was assessed by reviewing 384 policy and strategy documents, rules, regulations, legislation, and guidelines on PA. We scored the documents by using the Comprehensive Analysis of Policy on Physical Activity (CAPPA) framework. Data to assess policy implementation and public participation were taken from the Thailand Report Card Survey 2021 (TRC2021), and the Thailand Surveillance on Physical Activity (SPA) 2021. Both surveys comprised over 5,000 nationally-representative samples from on-screen, face-to-face interviews, and an online self-administered survey. We scored the policy implementation and public participation based on respondents' response towards policy implementation and participation indicators. A grading scheme was applied to indicate how successful an investment has been made. Results: Public education and mass media received the highest average score in policy availability, implementation and public participation in PA program (67.9%, grade B), followed by active urban design (66.1%, grade B-) and active transport (63.7%, grade B-). Workplace, whole-of-school, and community-wide initiatives were the investments with the lowest scores, implying low availability, limited implementation, and less accessibility to public. Females were less likely to participate in active transport, active urban design, sports/recreation for all, workplace activity, and community-wide initiatives. Age and educational attainment were consistent predictors of utilization in all investments. Conclusions: With varying degrees of policy availability and accessibility, public participation in PA investments is likely to be constrained by biological and socioeconomic inequality. Future investments should aim at providing generalized or tailored interventions to ensure equal access and participation for all segments of the population. [ABSTRACT FROM AUTHOR]

Introduction In epithelial cancers, truncated O -glycans, such as the Thomson-nouveau antigen (Tn) and its sialylated form (STn), are upregulated on the cell surface and associated with poor prognosis and immunological escape. Recent studies have shown that these carbohydrate epitopes facilitate cancer development and can be targeted therapeutically; however, the mechanism underpinning their expression remains unclear. Methods To identify genes directly influencing the expression of cancer-associated O -glycans, we conducted an unbiased, positive-selection, whole-genome CRISPR knockout-screen using monoclonal antibodies against Tn and STn. Results and Conclusions We show that knockout of the Zn2+-transporter SLC39A9 (ZIP9), alongside the well-described targets C1GALT1 (C1GalT1) and its molecular chaperone, C1GALT1C1 (COSMC), results in surface-expression of cancer-associated O -glycans. No other gene perturbations were found to reliably induce O -glycan truncation. We furthermore show that ZIP9 knockout affects N -linked glycosylation, resulting in upregulation of oligo-mannose, hybrid-type, and α2,6-sialylated structures as well as downregulation of tri- and tetra-antennary structures. Finally, we demonstrate that accumulation of Zn2+ in the secretory pathway coincides with cell-surface presentation of truncated O -glycans in cancer tissue, and that over-expression of COSMC mitigates such changes. Collectively, the findings show that dysregulation of ZIP9 and Zn2+ induces cancer-like glycosylation on the cell surface by affecting the glycosylation machinery. [ABSTRACT FROM AUTHOR]

This study addresses the gap in understanding the diversity, species, and functional trait distribution of different algal groups that occur in the Okavango Delta (a near-pristine subtropical wetland in northwestern Botswana) across hydrological and habitat gradients. We systematically characterize the delta's algal flora, addressing the gap left by previous research that was limited to single algal groups (e.g., diatoms) and/or only looking at upstream areas in the Okavango River basin. We analyzed 130 algal samples from 49 upstream and downstream sites with higher and lower flooding frequency, respectively, across a river-to-floodplain habitat gradient. Chlorophyta and Bacillariophyta dominated both abundance and taxon richness (>80%) of the total 494 taxa found from 49,158 algal units counted (cells, colonies, coenobia, and filaments). Smaller algae were more abundant in downstream floodplains than in upstream channels and lagoons. Motile and siliceous algae were much more abundant than non-motile, nitrogen fixing, and phagotrophic algae. The frequency of these traits was associated more with flooding frequency than habitat type. The highest algal richness and diversity were found downstream, where shallow floodplain ecosystems with seasonally fluctuating water depths offer greater habitat heterogeneity, and macronutrients are resuspended. The increasing threats from upstream water abstraction plans, fracking, and climate change require enhanced protection and monitoring of the Okavango Delta's natural annual flood-pulse to maintain the high species and functional diversity of this unique wetland's microalgae. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common cause of dementia and is classically characterized by two major histopathological abnormalities: extracellular plaques composed of amyloid beta (Aβ) and intracellular hyperphosphorylated tau. Due to the progressive nature of the disease, it is of the utmost importance to develop disease-modifying therapeutics that tackle AD pathology in its early stages. Attenuation of hippocampal hyperactivity, one of the earliest neuronal abnormalities observed in AD brains, has emerged as a promising strategy to ameliorate cognitive deficits and abate the spread of neurotoxic species. This aberrant hyperactivity has been attributed in part to the dysfunction of voltage-gated Na+ (Nav) channels, which are central mediators of neuronal excitability. Therefore, targeting Nav channels is a promising strategy for developing disease-modifying therapeutics that can correct aberrant neuronal phenotypes in early-stage AD. This review will explore the role of Nav channels in neuronal function, their connections to AD pathology, and their potential as therapeutic targets. [ABSTRACT FROM AUTHOR]

Methods for assessing three-dimensional (3D) breast volume are becoming increasingly popular in breast surgery. However, the precision of intraoperative volumetric assessment is still unclear. Until now, only non-validated scanning systems have been used for intraoperative volumetric analyses. This study aimed to assess the feasibility, handling, and accuracy of a commercially available, validated, and portable device for intraoperative 3D volumetric evaluation. All patients who underwent breast surgery from 2020 to 2022 were identified from our institutional database. Intraoperative 3D volumetric assessments of 103 patients were included in this study. Standardized 3D volumetric measurements were obtained 3 months postoperatively to compare the intraoperatively generated volumetric assessment. All of the study participants were women with a mean age of 48.3 ± 14.7 years (range: 20–89). The mean time for intraoperative volumetric assessment was 8.7 ± 2.6 min. The postoperative 3D volumetric assessment, with a mean volume of 507.11 ± 206.29 cc, showed no significant difference from the intraoperative volumetric measurements of 504.24 ± 276.61 cc (p = 0.68). The mean absolute volume difference between the intraoperative simulations and postoperative results was 27.1 cc. Intraoperative 3D volumetric assessment using the VECTRA H2 imaging system seems to be a feasible, reliable, and accurate method for measuring breast volume. Based on this finding, we plan to investigate whether volumetric objective evaluations will help to improve breast symmetry in the future. [ABSTRACT FROM AUTHOR]

Diverse extracellular and intracellular cues activate mammalian mitogen-activated protein kinases (MAPKs). Canonically, the activation starts at cell surface receptors and continues via intracellular MAPK components, acting in the host cell nucleus as activators of transcriptional programs to regulate various cellular activities, including proinflammatory responses against bacterial pathogens. For instance, binding host pattern recognition receptors (PRRs) on the surface of intestinal epithelial cells to bacterial pathogen external components trigger the MAPK/NF-κB signaling cascade, eliciting cytokine production. This results in an innate immune response that can eliminate the bacterial pathogen. However, enteric bacterial pathogens evolved sophisticated mechanisms that interfere with such a response by delivering virulent proteins, termed effectors, and toxins into the host cells. These proteins act in numerous ways to inactivate or activate critical components of the MAPK signaling cascades and innate immunity. The consequence of such activities could lead to successful bacterial colonization, dissemination, and pathogenicity. This article will review enteric bacterial pathogens' strategies to modulate MAPKs and host responses. It will also discuss findings attempting to develop anti-microbial treatments by targeting MAPKs. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is one of the leading causes of death in women, globally. A variety of biological processes results in metastasis, a poorly understood pathological phenomenon, causing a high relapse rate. Glycosylation, microribonucleic acids (miRNAs) and epithelial to mesenchymal transition (EMT), have been shown to regulate this cascade where tumor cells detach from their primary site, enter the circulatory system and colonize distant sites. Integrated proteomics and glycomics approaches have been developed to probe the molecular mechanism regulating such metastasis. In this review, we describe specific aspects of glycosylation and its interrelation with miRNAs, EMT and multidrug resistance during BC progression and metastasis. We explore various approaches that determine the role of proteomes and glycosylation in BC diagnosis, therapy and drug discovery. [ABSTRACT FROM AUTHOR]