Disorder regulates homeostasis of extracytoplasmic proteins in streptococci.

Proteins harboring intrinsically disordered regions (IDRs) that lack regular secondary or tertiary structure are abundant across three domains of life. Here, using a deep neural network (DNN)-based method we predict IDRs in the extracytoplasmic proteome of Streptococcus mutans , Streptococcus pyogenes and Streptococcus pneumoniae . We identify a subset of the serine/threonine-rich IDRs and demonstrate that they are O -glycosylated with glucose by a GtrB-like glucosyltransferase in S. pyogenes and S. pneumoniae , and N-acetylgalactosamine by a Pgf-dependent mechanism in S. mutans . Loss of glycosylation leads to a defect in biofilm formation under ethanol-stressed conditions in S. mutans . We link this phenotype to a C-terminal IDR of peptidyl-prolyl isomerase PrsA which is protected from proteolytic degradation by O -glycosylation. The IDR length attenuates the efficiency of glycosylation and expression of PrsA. Taken together, our data support a model in which extracytoplasmic IDRs function as dynamic switches of protein homeostasis in streptococci.

Functional and biochemical characterisation of remote homologues of type IV pili proteins PilN and PilO in Helicobacter pylori.

Helicobacter pylori encodes homologues of PilM, PilN and PilO from bacteria with Type IV pili, where these proteins form a pilus alignment complex. Inactivation of pilO changes H. pylori motility in semi-solid media, suggesting a link to the chemosensory pathways or flagellar motor. Here, we showed that mutation of the pilO or pilN gene in H. pylori strain SS1 reduced the mean linear swimming speed in liquid media, implicating PilO and PilN in the function, or regulation of, the flagellar motor. We also demonstrated that the soluble variants of H. pylori PilN and PilO share common biochemical properties with their Type IV pili counterparts which suggests their adapted function in the bacterial flagellar motor may be similar to that in the Type IV pili.

Low-Level Laser Therapy for Thumb Carpometacarpal Joint Osteoarthritis: A Randomized Controlled Trial.

Background and aim Low-level laser therapy (LLLT) is considered a promising non-invasive treatment option for osteoarthritis (OA). The current study aimed to evaluate the effectiveness of LLLT on patients with OA of the first carpometacarpal joint (CMC1) of the thumb. Methods An open-level, prospective, randomized controlled trial was conducted in the Department of Physical Medicine and Rehabilitation, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, for one year. Initially, 120 patients were approached for the study. Among them, 112 eligible patients were randomly divided into two groups: the intervention group received LLLT in addition to conservative treatment, while the control group received conservative treatment alone for four weeks. Pain and functional capability (motor) improvement were assessed on a weekly follow-up basis by using various parameters such as the visual analogue scale (VAS), Ritchie articular index (tenderness scale), grip strength, key pinch strength, Dreiser functional index, and CMC1 palmer abduction. Eventually, 90 patients completed the follow-ups and were included in the analysis. Results The majority of patients diagnosed with CMC1 joint OA were in their fifties. At baseline, patients of both intervention and control groups were indifferent in terms of demography, pain intensity, motor responses, and duration of suffering. After four weeks of treatment, results indicated an overall improvement in both groups. However, the reduction of pain and increase in functional capability were not found statistically significant (p-value: ≥0.5). Conclusion LLLT with conventional treatment was not found significantly more effective enough than conventional treatment alone, but more well-designed clinical trials with larger sample sizes are needed to reach a definitive conclusion.

Exploring the application of CHATGPT in plastic surgery: a comprehensive systematic review.

OBJECTIVE: To determine the impact of ChatGPT in plastic surgery research and assess the authenticity of such contributions. METHODS: The study conducted a literature search in Sep'23 from databases like Pubmed, Google Scholar, SCOPUS, and OVID Medline.The following keywords 'ChatGPT', 'chatbot', 'reconstruction', 'aesthetic' and 'plastic surgery' were used. 32 papers were included from the initial 131 results of articles. English language articles from November 2022 to July 2023 discussing ChatGPT's role in plastic and aesthetic surgery were included whereas non-English documents, irrelevant content, and non-academic sources were excluded from the study. RESULTS: The manuscripts included in the systematic review had a diverse range, including original research articles, case reports, letters to the editor, and editorials. Among the included studies, there were 9 original research articles, 1 case report, 23 letters to the editor, and 2 editorials. Most publications originated from the United States (18) and Australia (7). Analysis suggested concerns, such as inaccuracies, plagiarism, outdated knowledge, and lack of personalized advice. Various authors recommend using ChatGPT as a supplementary tool rather than a replacement for human decision-making in medicine. CONCLUSIONS: ChatGPT shows potential in plastic surgery research, concerns about inaccuracies and outdated knowledge may provide deceiving information and it always requires human input and verification.

Robotic-assisted free flap harvesting for diverse soft tissue reconstruction: a PRISMA scoping review of clinical outcomes over the last decade.

Introduction: The aim of our study was to assess the advantages and limitations of robotic technology in diverse reconstructive procedures. METHODS: A scoping review was conducted in Oct'23, on published studies from 2013 to 2023, focussing on robotic-assisted free flap harvesting. Three databases Ovid-MEDLINE, Scopus, and PubMed were searched. Original research studies reporting robotic-assisted free flap harvest were included. Studies on lesion excision, microvascular anastomosis, local flap harvest, roboticassisted flap inset, review articles, abstract-only studies, non-English documents, and animal studies were excluded from this review. RESULTS: Sixteen studies met the inclusion criteria out of a total of 318, searched initially. These studies included a total of 128 patients, who underwent robotic-assisted free flap harvest for the reconstruction of various defects, with 140 free flaps harvested. The most common flaps harvested by robotic technique were deep inferior epigastric artery perforator (DIEP) flap 120 (85.7%), radial forearm free (RFF) flap 11 (7.9%), latissimus dorsii flap 4 (2.9%), rectus abdominus flap 4 (2.9%), and omental flap 1 (0.7%). Breast reconstruction was the major procedure done i.e. 120 (85.7%) followed by head and neck 11 (7.9%) and limb defects 9 (6.4%) reconstruction procedures. The reported clinical outcomes were acceptable in all the studies with a 99% flap success rate and minimal complications. Variability in operating time was observed depending upon surgical steps undertaken with robotic systems. CONCLUSIONS: This scoping review highlights the role of robotic-assisted free flap harvesting in plastic surgery and its potential benefits on clinical outcomes, due to its high precision and minimal invasiveness. However, challenges like cost effectiveness, resource distribution and learning curve are there.

Phase separation, aggregation, and complexation of triton-X100 and bovine serum albumin mixture: A combined cloud point and UV-visible spectroscopic approaches.

Phase separation and aggregation behaviour of triton X-100 (TX-100) and bovine serum albumin (BSA) mixture were investigated using cloud point and UV-visible spectroscopic techniques. The effects of various hydrotropes (HYTs) - namely, sodium salicylate (SS), sodium benzoate (SB), glycerol (Glyc), and 4-aminobenzoic acid (4-ABA) - on the cloud point (CP) of TX-100 + BSA were determined. The obtained CP values for the mixed system in the presence of HYTs followed the order: The measured critical micellization concentration (CMC) values of the TX-100 + BSA mixture were found to be significantly altered with varying amounts of BSA. The calculated free energy of clouding and micellization indicated the non-spontaneous nature of the phase transition and the spontaneous association of the TX-100 + BSA mixture. The non-spontaneity of phase separation decreased with increasing concentrations of HYTs. The enumerated values of ∆Hco and ∆Sco were consistently recorded as negative and positive magnitudes, respectively, in all aqueous HYTs media. The clouding process occurred due to a combination of hydrophobic and electrostatic interactions. The binding constant of the mixed system was determined employing the UV-vis spectroscopic method using the Benesi-Hildebrand equation.

Hydrogeochemical characteristics of groundwater contamination in Guwahati city, Assam, India: Tracing the elemental Threads.

Groundwater serves as an important resource for drinking and agriculture in many countries, including India. Assessing the quality of groundwater is essential for understanding its chemical characteristics and suitability for consumption. This study aims to explore the factors affecting the hydrogeochemical changes in groundwater within Guwahati City, Assam, India. Groundwater samples were collected and analyzed for major and trace elements, as well as anion concentrations. Concentrations of As, Al, Ba, Cu, F-, Fe, Mn, and Pb exceeded the permissible limits set by both World Health Organization (WHO) and Bureau of Indian Standards (BIS), indicating serious health concerns for the local inhabitants. The distribution pattern of trace elements exceeding the guideline values is intricate, suggesting widespread contamination of groundwater throughout the study area. The Heavy Metal Pollution Index (HPI) and Water Quality Index (WQI) revealed that, except for the central zone, groundwater across the entire study area requires intervention. Piper plot illustrated that the groundwater is predominantly of Ca-HCO3 type, indicating the dominance of alkaline earth and weak acids. Groundwater hydrogeochemistry is mainly controlled by rock-water interaction and evolves through silicate weathering, carbonate weathering, and cation exchange processes. Multivariate statistical analysis identified distinct groups of groundwater based on chemical characteristics, emphasizing the role of both natural processes and anthropogenic activities in influencing groundwater quality. Regular monitoring, management, and intervention of groundwater sources throughout the study area are crucial for long-term use. The findings of this study will assist stakeholders, regulators, and policymakers in formulating strategies for the sustainable use of groundwater.

Epigenome-wide association study of lung cancer among never smokers in two prospective cohorts in Shanghai, China.

BACKGROUND: The aetiology of lung cancer among individuals who never smoked remains elusive, despite 15% of lung cancer cases in men and 53% in women worldwide being unrelated to smoking. Epigenetic alterations, particularly DNA methylation (DNAm) changes, have emerged as potential drivers. Yet, few prospective epigenome-wide association studies (EWAS), primarily focusing on peripheral blood DNAm with limited representation of never smokers, have been conducted. METHODS: We conducted a nested case-control study of 80 never-smoking incident lung cancer cases and 83 never-smoking controls within the Shanghai Women's Health Study and Shanghai Men's Health Study. DNAm was measured in prediagnostic oral rinse samples using Illumina MethylationEPIC array. Initially, we conducted an EWAS to identify differentially methylated positions (DMPs) associated with lung cancer in the discovery sample of 101 subjects. The top 50 DMPs were further evaluated in a replication sample of 62 subjects, and results were pooled using fixed-effect meta-analysis. RESULTS: Our study identified three DMPs significantly associated with lung cancer at the epigenome-wide significance level of p<8.22×10-8. These DMPs were identified as cg09198866 (MYH9; TXN2), cg01411366 (SLC9A10) and cg12787323. Furthermore, examination of the top 1000 DMPs indicated significant enrichment in epithelial regulatory regions and their involvement in small GTPase-mediated signal transduction pathways. Additionally, GrimAge acceleration was identified as a risk factor for lung cancer (OR=1.19 per year; 95% CI 1.06 to 1.34). CONCLUSIONS: While replication in a larger sample size is necessary, our findings suggest that DNAm patterns in prediagnostic oral rinse samples could provide novel insights into the underlying mechanisms of lung cancer in never smokers.

A comprehensive review on phytochemicals in the treatment and prevention of pancreatic cancer: Focusing on their mechanism of action.

Background and Aims: Pancreatic cancer develops in the normal tissues of the pancreas from malignant cells. The chance of recovery is not good, and the chance of survival 5 years following diagnosis is quite low. Pancreatic cancer treatment strategies such as radiotherapy and chemotherapy had relatively low success rates. Therefore, the present study aims to explore new therapies for treating pancreatic cancer. Methods: The present study searched for information about pancreatic cancer pathophysiology, available treatment options; and their comparative benefits and challenges. Aiming to identify potential alternative therapeutics, this comprehensive review analyzed information from renowned databases such as Scopus, PubMed, and Google Scholar. Results: In recent years, there has been a rise in interest in the possibility that natural compounds could be used as treatments for cancer. Cannabinoids, curcumin, quercetin, resveratrol, and triptolide are some of the anticancer phytochemicals now used to manage pancreatic cancer. The above compounds are utilized by inhibiting or stimulating biological pathways such as apoptosis, autophagy, cell growth inhibition or reduction, oxidative stress, epithelial-mesenchymal transformation, and increased resistance to chemotherapeutic drugs in the management of pancreatic cancer. Conclusion: Right now, surgery is the only therapeutic option for patients with pancreatic cancer. However, most people who get sick have been diagnosed too late to benefit from potentially effective surgery. Alternative medications, like natural compounds and herbal medicines, are promising complementary therapies for pancreatic cancer. Therefore, we recommend large-scale standardized clinical research for the investigation of natural compounds to ensure their consistency and comparability in pancreatic cancer treatment.

Gender differences in the prevalence of anxiety and depression and care seeking for mental health problems in Nepal: Analysis of nationally representative survey data.

Background: Assessing gender disparity in mental health is crucial for targeted interventions. This study aims to quantify gender disparities in mental health burdens, specifically anxiety and depression, and related care-seeking behaviors across various sociodemographic factors in Nepal, highlighting the importance of gender-specific mental health interventions. Methods: Data from the 2022 Nepal Demographic and Health Survey was utilized, employing the Generalized Anxiety Disorder 7 scale (GAD-7) and Patient Health Questionnaire (PHQ-9) scales for anxiety and depression symptoms, respectively. Multiple logistic regression models assessed gender associations with these conditions and care-seeking behaviors. Results: Women had a higher point prevalence of anxiety (21.9% vs. 11.3%) and depression (5.4% vs. 1.7%) than men. Large variations were noted in gender disparities in the prevalence of anxiety and depression, influenced by age, geographical areas, level of education and household wealth. After adjustment for sociodemographic factors, women were more likely to experience anxiety (adjusted odds ratio (aOR) = 2.18, 95% confidence interval [CI]: 1.96-2.43) and depression (aOR = 3.21, 95% CI: 2.53-4.07). However, no difference was observed in the rates of seeking care for anxiety or depression (aOR = 1.13, 95% CI: 0.91-1.40). Conclusions: Our findings show a higher point prevalence of mental health issues among women than men, influenced by sociodemographic factors, underscoring the need for gender-focused mental health interventions in Nepal and globally.

Thermal and structural characteristics of date-pits as digested by Trichoderma reesei.

The objective of this study was to develop functional date-pits by mold digestion for the potential use in food products. Whole date-pits (WDP) and defatted date-pits (DDP) were digested by mold Trichoderma reesei at 20 °C. T. reesei consumed date-pits as nutrients for their growth, and DDP showed higher growth of molds as compared to the WDP. The mold digested WDP and DDP samples showed an increased water solubility and hygroscopicity as compared to the samples prepared by autoclaved. This indicated that the mold digestion transformed date-pits to hydrophilic characteristics. Thermal analysis indicated a structural change at -3.2 °C for the untreated WDP and it was followed by a glass transition shift (i.e. onset: 138 °C and a specific heat change: 295 J/kg oC), and an endothermic peak at 196 °C with enthalpy of 68 J/g for the solids melting-decomposition. Similar characteristics were also observed for treated samples with the two glass transitions. The total specific heat changes for WDP, autoclaved-WDP, and digested-WDP were observed as 295, 367, and 328 J/kg oC, respectively. The total specific heat changes for DDP, autoclaved-DDP, and digested-DDP were observed as 778, 1329, and 1877 J/kg oC, respectively. This indicated that mold digestion transformed more amorphous fraction in the DDP. The energy absorption intensities of the Fourier Transform Infrared (FTIR) spectra for the selected functional groups decreased by the mold digestion.

Lunar Age-Dependent Oscillations in Expression of the Genes for Kisspeptin, GnIH, and Their Receptors in the Grass Puffer during the Spawning Season.

Grass puffer is a semilunar-synchronized spawner: spawning occurs on beaches only for several days of spring tide around new moon (lunar age 0) and full moon (lunar age 15) every 2 weeks from spring to early summer. To investigate the role of kisspeptin and gonadotropin-inhibitory hormone (GnIH) in the semilunar-synchronized spawning, lunar age-dependent expression of the genes encoding kisspeptin (kiss2), kisspeptin receptor (kissr2), GnIH (gnih), GnIH receptor (gnihr), gonadotropin-releasing hormone 1 (GnRH1) (gnrh1), and three gonadotropin (GTH) subunits (gpa, fshb, lhb) was examined in the male grass puffer, which was kept in an aquarium under natural light condition in a lunar month during the spawning period. In the brain, both kiss2 and kissr2 showed lunar variations with a peak at lunar age 10, while both gnih and gnihr showed semilunar variations with two peaks at lunar age 0 and 20. On the other hand, gnrh1 showed semilunar variation with two peaks at lunar age 0 and 15. In the pituitary, kiss2, kissr2, gnih, and gnihr showed similar variations to those shown in the brain. The fshb and lhb mRNA levels showed semilunar variations with two peaks at lunar age 0 and 15. The present study shows lunar and semilunar oscillations of kiss2/kissr2 and gnih/gnihr expressions, respectively, with their peaks around spring tide in the brain and pituitary along with the semilunar expressions of gnrh1 and the pituitary GTH subunit genes. These results suggest that the lunar age-dependent expressions of the kisspeptin, GnIH, and their receptor genes may be primarily important in the control of the precisely timed semilunar spawning of the grass puffer.

Fine Motor Skills, a Surrogate of Motor Planning Ability, at Age 2 Predict Social Skills at Age 6.

OBJECTIVES: Motor planning is the cognitive process of planning necessary steps for achieving a purposeful movement and is specifically reflected through object manipulation. This study aimed to investigate whether fine motor skills, a surrogate of the motor planning ability of object manipulation, in early childhood are associated with later social skills, in a general-population birth cohort. METHODS: A total of 913 children, participating in the Hamamatsu Birth Cohort for Mothers and Children, were enrolled. Social skills were measured using the Vineland Adaptive Behavior Scales-II, Socialization domain, at age 6 years. Fine motor skills were measured using the Mullen Scales of Early Learning at 14, 24, and 32 months. The associations between fine motor skills at ages 14, 24, and 32 months and social skills at age 6 years were tested separately through multivariable linear regression after adjusting for covariates, including gross motor and language skills at the contemporaneous age, autistic symptoms at age 6 years, and demographic factors. RESULTS: Fine motor skills at 24 and 32 months were significantly associated with social skills at age 6 years (at 24 months: nonstandardized regression coefficient = 1.38 [95% CI, 0.50-2.26], p = 0.002; at 32 months: 1.47 [0.56-2.38], p = 0.001). CONCLUSION: Fine motor skills in early childhood predicted social skills at age 6 years, indicating an association between the complex motor planning ability of object manipulation and later social skills. Children who demonstrate fine motor delay at as early an age as 2 years should be closely monitored by child professionals.

A nested case-control study of untargeted plasma metabolomics and lung cancer among never-smoking women within the prospective Shanghai Women's Health Study.

The etiology of lung cancer in never-smokers remains elusive, despite 15% of lung cancer cases in men and 53% in women worldwide being unrelated to smoking. Here, we aimed to enhance our understanding of lung cancer pathogenesis among never-smokers using untargeted metabolomics. This nested case-control study included 395 never-smoking women who developed lung cancer and 395 matched never-smoking cancer-free women from the prospective Shanghai Women's Health Study with 15,353 metabolic features quantified in pre-diagnostic plasma using liquid chromatography high-resolution mass spectrometry. Recognizing that metabolites often correlate and seldom act independently in biological processes, we utilized a weighted correlation network analysis to agnostically construct 28 network modules of correlated metabolites. Using conditional logistic regression models, we assessed the associations for both metabolic network modules and individual metabolic features with lung cancer, accounting for multiple testing using a false discovery rate (FDR) < 0.20. We identified a network module of 121 features inversely associated with all lung cancer (p = .001, FDR = 0.028) and lung adenocarcinoma (p = .002, FDR = 0.056), where lyso-glycerophospholipids played a key role driving these associations. Another module of 440 features was inversely associated with lung adenocarcinoma (p = .014, FDR = 0.196). Individual metabolites within these network modules were enriched in biological pathways linked to oxidative stress, and energy metabolism. These pathways have been implicated in previous metabolomics studies involving populations exposed to known lung cancer risk factors such as traffic-related air pollution and polycyclic aromatic hydrocarbons. Our results suggest that untargeted plasma metabolomics could provide novel insights into the etiology and risk factors of lung cancer among never-smokers.

Mechanism of antagonist ligand binding to REV-ERBα.

REV-ERBα, a therapeutically promising nuclear hormone receptor, plays a crucial role in regulating various physiological processes such as the circadian clock, inflammation, and metabolism. However, the availability of chemical probes to investigate the pharmacology of this receptor is limited, with SR8278 being the only identified synthetic antagonist. Moreover, no X-ray crystal structures are currently available that demonstrate the binding of REV-ERBα to antagonist ligands. This lack of structural information impedes the development of targeted therapeutics. To address this issue, we employed Gaussian accelerated molecular dynamics (GaMD) simulations to investigate the binding pathway of SR8278 to REV-ERBα. For comparison, we also used GaMD to observe the ligand binding process of STL1267, for which an X-ray structure is available. GaMD simulations successfully captured the binding of both ligands to the receptor's orthosteric site and predicted the ligand binding pathway and important amino acid residues involved in the antagonist SR8278 binding. This study highlights the effectiveness of GaMD in investigating protein-ligand interactions, particularly in the context of drug recognition for nuclear hormone receptors.

The CB1 negative allosteric modulator PSNCBAM-1 reduces ethanol self-administration via a nonspecific hypophagic effect.

Alcohol use disorder (AUD) affects >15 million people in the United States. Current pharmacotherapeutic treatments for AUD are only modestly effective, necessitating the identification of new targets for medications development. The cannabinoid receptor type 1 (CB1) has been a target of interest for the development of medications for substance use disorders and other compulsive disorders. However, CB1 antagonists/inverse agonists (e.g., rimonabant) have severe side effects that limit their clinical utility, including anxiety, depression, and suicide. Recent development of CB1 negative allosteric modulators (NAMs), including PSNCBAM-1, may provide an alternative mechanism of attenuating CB1 signaling with reduced side effects. PSNCBAM-1 has not yet been evaluated for effects in models of AUD. In this study, we investigated the effects of the CB1 NAM, PSNCBAM-1, in rodent models of AUD using adult male mice. PSNCBAM-1 dose-dependently attenuated oral ethanol self-administration (8 % w/v ethanol in water), significantly reducing ethanol rewards at a dose of 30 mg/kg, but not at 10 or 18 mg/kg. PSNCBAM-1 also dose-dependently attenuated palatable food self-administration (diluted vanilla Ensure), significantly reducing food rewards at 18 and 30 mg/kg PSNCBAM-1. PSNCBAM-1 did not affect conditioned place preference for 2 g/kg ethanol. These results suggest PSNCBAM-1 reduces ethanol-taking behavior via a nonspecific hypophagic effect and does not reduce the rewarding effects of ethanol.

Complete Rescue of HTLV-1p12KO Infectivity by Depletion of Monocytes Together with NK and CD8+ T Cells.

The transient depletion of monocytes alone prior to exposure of macaques to HTLV-1 enhances both HTLV-1WT (wild type) and HTLV-1p12KO (Orf-1 knockout) infectivity, but seroconversion to either virus is not sustained over time, suggesting a progressive decrease in virus expression. These results raise the hypotheses that either HTLV-1 persistence depends on a monocyte reservoir or monocyte depletion provides a transient immune evasion benefit. To test these hypotheses, we simultaneously depleted NK cells, CD8+ T cells, and monocytes (triple depletion) prior to exposure to HTLV-1WT or HTLV-1p12KO. Remarkably, triple depletion resulted in exacerbation of infection by both viruses and complete rescue of HTLV-1p12KO infectivity. Following triple depletion, we observed rapid and sustained seroconversion, high titers of antibodies against HTLV-1 p24Gag, and frequent detection of viral DNA in the blood and tissues of all animals when compared with depletion of only CD8+ and NK cells, or monocytes alone. The infection of macaques with HTLV-1WT or HTLV-1p12KO was associated with higher plasma levels of IL-10 after 21 weeks, while IL-6, IFN-γ, IL-18, and IL-1ß were only elevated in animals infected with HTLV-1WT. The repeat depletion of monocytes, NK, and CD8+ cells seven months following the first exposure to HTLV-1 did not further exacerbate viral replication. These results underscore the contribution of monocytes in orchestrating anti-viral immunity. Indeed, the absence of orf-1 expression was fully compensated by the simultaneous depletion of CD8+ T cells, NK cells, and monocytes, underlining the primary role of orf-1 in hijacking host immunity.

Tea (Camellia sinensis) cultivated in three agro-ecological regions of Bangladesh: Unveiling the variability of methylxanthine, bioactive phenolic compound, and antioxidant activity.

Tea (Camellia sinensis) is a widely consumed beverage known for its numerous health benefits, largely attributed to its rich content of quality determining secondary metabolites such as methylxanthine compounds and bioactive phenolic compounds. The goal of this study was to find out variations of the levels of methylxanthines, bioactive phenolic compounds, and antioxidant activity in methanolic and hot water extracts of 129 tea samples grown in three different ecological regions of Bangladesh named Panchagar, Sylhet, and Chattogram. Methylxanthine and bioactive phenolic compounds were determined by using HPLC-DAD, and the antioxidant profile was analysed by UV-vis spectrophotometric methods for methanol and hot water extracts of tea leaves. The IC50 values showed the trend as Panchagar > Sylhet > Chattogram and Sylhet > Chattogram > Panchagar for water and methanol extract, respectively. The results revealed significant (p < 0.05) variations in the levels of methylxanthines content: Panchagar > Chattogram > Sylhet. Caffeine was significantly higher (103.02 ± 5.55 mg/g of dry extract) in the methanolic extract of tea leaves of Panchagar district and lower (53.33 ± 4.30 mg/g of dry extract) in the hot water extract of Sylhet district. Panchagar and Chattogram possessed significantly (p < 0.05) higher catechin content for methanol (57.01 ± 5.50 mg/g dry extract) and hot water (55.23 ± 4.11 mg/g dry extract) extracts, respectively. The utilization of canonical discriminant functions yielded highly favorable outcomes in the classification of tea from three distinct cultivation origins in Bangladesh, relying on their inherent features. This study demonstrated the potential effects of geographical variations on the bioactive compounds and antioxidant properties of tea, emphasizing the importance of regional differences in tea cultivation for optimizing its health benefits as well as dispersing tea cultivation across the country.

Unveiling the health consequences of air pollution in the world's most polluted nations.

Air pollution poses a persuasive threat to global health, demonstrating widespread detrimental effects on populations worldwide. Exposure to pollutants, notably particulate matter with a diameter of 2.5 µm (PM2.5), has been unequivocally linked to a spectrum of adverse health outcomes. A nuanced understanding of the relationship between them is crucial for implementing effective policies. This study employs a comprehensive investigation, utilizing the extended health production function framework alongside the system generalized method of moments (SGMM) technique, to scrutinize the interplay between air pollution and health outcomes. Focusing on a panel of the top twenty polluted nations from 2000 to 2021, the findings yield substantial insights. Notably, PM2.5 concentration emerges as a significant factor, correlating with a reduction in life expectancy by 3.69 years and an increase in infant mortality rates by 0.294%. Urbanization is found to increase life expectancy by 0.083 years while concurrently decreasing infant mortality rates by 0.00022%. An increase in real per capita gross domestic product corresponds with an improvement in life expectancy by 0.21 years and a decrease in infant mortality rates by 0.00065%. Similarly, an elevated school enrollment rate is associated with a rise in life expectancy by 0.17 years and a decline in infant mortality rates by 0.00032%. However, a higher population growth rate is found to modestly decrease life expectancy by 0.019 years and slightly elevate infant mortality rates by 0.000016%. The analysis reveals that per capita greenhouse gas emissions exert a negative impact, diminishing life expectancy by 0.486 years and elevating infant mortality rates by 0.00061%, while per capita energy consumption marginally reduces life expectancy by 0.026 years and increases infant mortality rates by 0.00004%. Additionally, economic volatility shock presents a notable decrement in life expectancy by 0.041 years and an increase in infant mortality rates by 0.000045%, with inflationary shock further exacerbating adverse health outcomes by lowering life expectancy by 0.70 years and elevating infant mortality rates by 0.00025%. Moreover, the study scrutinizes the role of institutional quality, revealing a constructive impact on health outcomes. Specifically, the institutional quality index is associated with an increase in life expectancy by 0.66% and a decrease in infant mortality rates by 0.0006%. Extending the analysis to examine the nuanced dimensions of institutional quality, the findings discern that economic institutions wield a notably stronger positive influence on health outcomes compared to political and institutional governance indices. Finally, the results underscore the pivotal moderating role of institutional quality in mitigating the deleterious impact of PM2.5 concentration on health outcomes, counterbalancing the influence of external shocks, and improving the relationships between explanatory variables and health outcome indicators. These findings offer critical insights for guiding evidence-based policy implications, with a focus on fostering resilient, sustainable, and health-conscious societies.

A prospective study of smoking-related white blood cell DNA methylation markers and risk of bladder cancer.

Bladder cancer, a common neoplasm, is primarily caused by tobacco smoking. Epigenetic alterations including DNA methylation have the potential to be used as prospective markers of increased risk, particularly in at-risk populations such as smokers. We aimed to investigate the potential of smoking-related white blood cell (WBC) methylation markers to contribute to an increase in bladder cancer risk prediction over classical questionnaire-based smoking metrics (i.e., duration, intensity, packyears) in a nested case-control study within the prospective prostate, lung, colorectal, and ovarian (PLCO) Cancer Screening Trial and the alpha-tocopherol, beta-carotene cancer (ATBC) Prevention Study (789 cases; 849 controls). We identified 200 differentially methylated sites associated with smoking status and 28 significantly associated (after correction for multiple testing) with bladder cancer risk among 2670 previously reported smoking-related cytosine-phosphate-guanines sites (CpGs). Similar patterns were observed across cohorts. Receiver operating characteristic (ROC) analyses indicated that cg05575921 (AHHR), the strongest smoking-related association we identified for bladder cancer risk, alone yielded similar predictive performance (AUC: 0.60) than classical smoking metrics (AUC: 0.59-0.62). Best prediction was achieved by including the first principal component (PC1) from the 200 smoking-related CpGs alongside smoking metrics (AUC: 0.63-0.65). Further, PC1 remained significantly associated with elevated bladder cancer risk after adjusting for smoking metrics. These findings suggest DNA methylation profiles reflect aspects of tobacco smoke exposure in addition to those captured by smoking duration, intensity and packyears, and/or individual susceptibility relevant to bladder cancer etiology, warranting further investigation.