Genetic ablation of synaptotagmin-9 alters tomosyn-1 function to increase insulin secretion from pancreatic ß-cells improving glucose clearance.

Stimulus-coupled insulin secretion from the pancreatic islet ß-cells involves the fusion of insulin granules to the plasma membrane (PM) via SNARE complex formation-a cellular process key for maintaining whole-body glucose homeostasis. Less is known about the role of endogenous inhibitors of SNARE complexes in insulin secretion. We show that an insulin granule protein synaptotagmin-9 (Syt9) deletion in mice increased glucose clearance and plasma insulin levels without affecting insulin action compared to the control mice. Upon glucose stimulation, increased biphasic and static insulin secretion were observed from ex vivo islets due to Syt9 loss. Syt9 colocalizes and binds with tomosyn-1 and the PM syntaxin-1A (Stx1A); Stx1A is required for forming SNARE complexes. Syt9 knockdown reduced tomosyn-1 protein abundance via proteasomal degradation and binding of tomosyn-1 to Stx1A. Furthermore, Stx1A-SNARE complex formation was increased, implicating Syt9-tomosyn-1-Stx1A complex is inhibitory in insulin secretion. Rescuing tomosyn-1 blocked the Syt9-knockdown-mediated increases in insulin secretion. This shows that the inhibitory effects of Syt9 on insulin secretion are mediated by tomosyn-1. We report a molecular mechanism by which ß-cells modulate their secretory capacity rendering insulin granules nonfusogenic by forming the Syt9-tomosyn-1-Stx1A complex. Altogether, Syt9 loss in ß-cells decreases tomosyn-1 protein abundance, increasing the formation of Stx1A-SNARE complexes, insulin secretion, and glucose clearance. These outcomes differ from the previously published work that identified Syt9 has either a positive or no effect of Syt9 on insulin secretion. Future work using ß-cell-specific deletion of Syt9 mice is key for establishing the role of Syt9 in insulin secretion.

[Fully Automatic Glioma Segmentation Algorithm of Magnetic Resonance Imaging Based on 3D-UNet With More Global Contextual Feature Extraction: An Improvement on Insufficient Extraction of Global Features]. / 3DGE-UNetç£å ±æŒ¯æˆåƒçš„è„‘èƒ¶è´¨ç˜¤å ¨è‡ªåŠ¨åˆ†å‰²ç®—æ³•ï¼šå¯¹ä¸å åˆ†å ¨å±€ç‰¹å¾æå–çš„æ”¹è¿›.

Objective: The fully automatic segmentation of glioma and its subregions is fundamental for computer-aided clinical diagnosis of tumors. In the segmentation process of brain magnetic resonance imaging (MRI), convolutional neural networks with small convolutional kernels can only capture local features and are ineffective at integrating global features, which narrows the receptive field and leads to insufficient segmentation accuracy. This study aims to use dilated convolution to address the problem of inadequate global feature extraction in 3D-UNet. Methods: 1) Algorithm construction: A 3D-UNet model with three pathways for more global contextual feature extraction, or 3DGE-UNet, was proposed in the paper. By using publicly available datasets from the Brain Tumor Segmentation Challenge (BraTS) of 2019 (335 patient cases), a global contextual feature extraction (GE) module was designed. This module was integrated at the first, second, and third skip connections of the 3D UNet network. The module was utilized to fully extract global features at different scales from the images. The global features thus extracted were then overlaid with the upsampled feature maps to expand the model's receptive field and achieve deep fusion of features at different scales, thereby facilitating end-to-end automatic segmentation of brain tumors. 2) Algorithm validation: The image data were sourced from the BraTs 2019 dataset, which included the preoperative MRI images of 335 patients across four modalities (T1, T1ce, T2, and FLAIR) and a tumor image with annotations made by physicians. The dataset was divided into the training, the validation, and the testing sets at an 8∶1∶1 ratio. Physician-labelled tumor images were used as the gold standard. Then, the algorithm's segmentation performance on the whole tumor (WT), tumor core (TC), and enhancing tumor (ET) was evaluated in the test set using the Dice coefficient (for overall effectiveness evaluation), sensitivity (detection rate of lesion areas), and 95% Hausdorff distance (segmentation accuracy of tumor boundaries). The performance was tested using both the 3D-UNet model without the GE module and the 3DGE-UNet model with the GE module to internally validate the effectiveness of the GE module setup. Additionally, the performance indicators were evaluated using the 3DGE-UNet model, ResUNet, UNet++, nnUNet, and UNETR, and the convergence of these five algorithm models was compared to externally validate the effectiveness of the 3DGE-UNet model. Results: 1) In internal validation, the enhanced 3DGE-UNet model achieved Dice mean values of 91.47%, 87.14%, and 83.35% for segmenting the WT, TC, and ET regions in the test set, respectively, producing the optimal values for comprehensive evaluation. These scores were superior to the corresponding scores of the traditional 3D-UNet model, which were 89.79%, 85.13%, and 80.90%, indicating a significant improvement in segmentation accuracy across all three regions (P<0.05). Compared with the 3D-UNet model, the 3DGE-UNet model demonstrated higher sensitivity for ET (86.46% vs. 80.77%) (P<0.05) , demonstrating better performance in the detection of all the lesion areas. When dealing with lesion areas, the 3DGE-UNet model tended to correctly identify and capture the positive areas in a more comprehensive way, thereby effectively reducing the likelihood of missed diagnoses. The 3DGE-UNet model also exhibited exceptional performance in segmenting the edges of WT, producing a mean 95% Hausdorff distance superior to that of the 3D-UNet model (8.17 mm vs. 13.61 mm, P<0.05). However, its performance for TC (8.73 mm vs. 7.47 mm) and ET (6.21 mm vs. 5.45 mm) was similar to that of the 3D-UNet model. 2) In the external validation, the other four algorithms outperformed the 3DGE-UNet model only in the mean Dice for TC (87.25%), the mean sensitivity for WT (94.59%), the mean sensitivity for TC (86.98%), and the mean 95% Hausdorff distance for ET (5.37 mm). Nonetheless, these differences were not statistically significant (P>0.05). The 3DGE-UNet model demonstrated rapid convergence during the training phase, outpacing the other external models. Conclusion: The 3DGE-UNet model can effectively extract and fuse feature information on different scales, improving the accuracy of brain tumor segmentation.

Graft-Host Interaction and Its Effect on Wound Repair Using Mouse Models.

Autologous skin grafting has been commonly used in clinics for decades to close large wounds, yet the cellular and molecular interactions between the wound bed and the graft that mediates the wound repair are not fully understood. The aim of this study was to better understand the molecular changes in the wound triggered by autologous and synthetic grafting. Defining the wound changes at the molecular level during grafting sets the basis to test other engineered skin grafts by design. In this study, a full-thickness skin graft (SKH-1 hairless) mouse model was established. An autologous full-thickness skin graft (FTSG) or an acellular fully synthetic Biodegradable Temporising Matrix (BTM) was grafted. The wound bed/grafts were analysed at histological, RNA, and protein levels during the inflammation (day 1), proliferation (day 5), and remodelling (day 21) phases of wound repair. The results showed that in this mouse model, similar to others, inflammatory marker levels, including Il-6, Cxcl-1, and Cxcl-5/6, were raised within a day post-wounding. Autologous grafting reduced the expression of these inflammatory markers. This was different from the wounds grafted with synthetic dermal grafts, in which Cxcl-1 and Cxcl-5/6 remained significantly high up to 21 days post-grafting. Autologous skin grafting reduced wound contraction compared to wounds that were left to spontaneously repair. Synthetic grafts contracted significantly more than FTSG by day 21. The observed wound contraction in synthetic grafts was most likely mediated at least partly by myofibroblasts. It is possible that high TGF-ß1 levels in days 1-21 were the driving force behind myofibroblast abundance in synthetic grafts, although no evidence of TGF-ß1-mediated Connective Tissue Growth Factor (CTGF) upregulation was observed.

The bioaccessibility of adsorped heavy metals on biofilm-coated microplastics and their implication for the progression of neurodegenerative diseases.

Microplastic (MP) tiny fragments (< 5 mm) of conventional and specialized industrial polymers are persistent and ubiquitous in both aquatic and terrestrial ecosystem. Breathing, ingestion, consumption of food stuffs, potable water, and skin are possible routes of MP exposure that pose potential human health risk. Various microorganisms including bacteria, cyanobacteria, and microalgae rapidly colonized on MP surfaces which initiate biofilm formation. It gradually changed the MP surface chemistry and polymer properties that attract environmental metals. Physicochemical and environmental parameters like polymer type, dissolved organic matter (DOM), pH, salinity, ion concentrations, and microbial community compositions regulate metal adsorption on MP biofilm surface. A set of highly conserved proteins tightly regulates metal uptake, subcellular distribution, storage, and transport to maintain cellular homeostasis. Exposure of metal-MP biofilm can disrupt that cellular homeostasis to induce toxicities. Imbalances in metal concentrations therefore led to neuronal network dysfunction, ROS, mitochondrial damage in diseases like Alzheimer's disease (AD), Parkinson's disease (PD), and Prion disorder. This review focuses on the biofilm development on MP surfaces, factors controlling the growth of MP biofilm which triggered metal accumulation to induce neurotoxicological consequences in human body and stategies to reestablish the homeostasis. Thus, the present study gives a new approach on the health risks of heavy metals associated with MP biofilm in which biofilms trigger metal accumulation and MPs serve as a vector for those accumulated metals causing metal dysbiosis in human body.

Toxicity assessment of polyethylene microplastics in combination with a mix of emerging pollutants on Physalaemus cuvieri tadpoles.

Studies in recent years have shown that aquatic pollution by microplastics (MPs) can be considered to pose additional stress to amphibian populations. However, our knowledge of how MPs affect amphibians is very rudimentary, and even more limited is our understanding of their effects in combination with other emerging pollutants. Thus, we aimed to evaluate the possible toxicity of polyethylene MPs (PE-MPs) (alone or in combination with a mix of pollutants) on the health of Physalaemus cuvieri tadpoles. After 30 days of exposure, multiple biomarkers were measured, including morphological, biometric, and developmental indices, behavioral parameters, mutagenicity, cytotoxicity, antioxidant and cholinesterase responses, as well as the uptake and accumulation of PE-MPs in animals. Based on the results, there was no significant change in any of the parameters measured in tadpoles exposed to treatments, but induced stress was observed in tadpoles exposed to PE-MPs combined with the mixture of pollutants, reflecting significant changes in physiological and biochemical responses. Through principal component analysis (PCA) and integrated biomarker response (IBR) assessment, effects induced by pollutants in each test group were distinguished, confirming that the exposure of P. cuvieri tadpoles to the PE-MPs in combination with a mix of emerging pollutants induces an enhanced stress response, although the uptake and accumulation of PE-MPs in these animals was reduced. Thus, our study provides new insight into the danger to amphibians of MPs coexisting with other pollutants in aquatic environments.

Lipoid Proteinosis: Identification of a Novel Nonsense Mutation c.1246C>T:p.R416X in ECM1 gene from Bangladesh.

Lipoid proteinosis is a rare multisystem genodermatosis inherited as autosomal recessive trait. We report a case of lipoid proteinosis in a 10-year-old boy born to first-degree consanguineous parents presented with marked hoarseness of voice, accelerated photoaging appearance, enlarged and erythematous tongue with restricted movement and widespread dermatoses. Biopsy of oral mucosa revealed Periodic acid-Schiff (PAS)-positive amorphous eosinophilic hyaline deposits. Mutational analysis revealed a homozygous nonsense mutation with C to T substitution at nucleotide position 1246(c.1246C>T) in exon-8 of the extracellular matrix protein 1 gene leading to a stop codon. Both the parents were unaffected heterozygous carriers. To our knowledge, this is the first case report of lipoid proteinosis with evidence of a novel nonsense genetic mutation from Bangladesh.

Mechanistic assessment of tolerance to iron deficiency mediated by Trichoderma harzianum in soybean roots.

AIMS: Iron (Fe) deficiency in soil is a continuing problem for soybean (Glycine max L.) production, partly as a result of continuing climate change. This study elucidates how Trichoderma harzianum strain T22 (TH) mitigates growth retardation associated with Fe-deficiency in a highly sensitive soybean cultivar. METHODS AND RESULTS: Soil TH supplementation led to mycelial colonization and the presence of UAOX1 gene in roots that caused substantial improvement in chlorophyll score, photosynthetic efficiency and morphological parameters, indicating a positive influence on soybean health. Although rhizosphere acidification was found to be a common feature of Fe-deficient soybean, the upregulation of Fe-reductase activity (GmFRO2) and total phenol secretion were two of the mechanisms that substantially increased the Fe availability by TH. Heat-killed TH applied to soil caused no improvement in photosynthetic attributes and Fe-reductase activity, confirming the active role of TH in mitigating Fe-deficiency. Consistent increases in tissue Fe content and increased Fe-transporter (GmIRT1, GmNRAMP2a, GmNRAMP2b and GmNRAMP7) mRNA levels in roots following TH supplementation were observed only under Fe-deprivation. Root cell death, electrolyte leakage, superoxide (O2 •- ) and hydrogen peroxide (H2 O2 ) substantially declined due to TH in Fe-deprived plants. Further, the elevation of citrate and malate concentration along with the expression of citrate synthase (GmCs) and malate synthase (GmMs) caused by TH suggest improved chelation of Fe in Fe-deficient plants. Results also suggest that TH has a role in triggering antioxidant defence by increasing the activity of glutathione reductase (GR) along with elevated S-metabolites (glutathione and methionine) to stabilize redox status under Fe-deficiency. CONCLUSIONS: TH increases the availability and mobilization of Fe by inducing Fe-uptake pathways, which appears to help provide resistance to oxidative stress associated with Fe-shortage in soybean. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings indicate that while Fe deficiency does not affect the rate or degree of TH hyphal association in soybean roots, the beneficial effects of TH alone may be Fe deficiency-dependent.

Green synthesis of gold nanoparticles using Gracilaria crassa leaf extract and their ecotoxicological potential: Issues to be considered.

The use of vegetal species for gold nanoparticles (AuNPs) biosynthesis can constitute an alternative to replacing the extensive use of several hazardous chemicals commonly used during NPs synthesis and, therefore, can reduce biological impacts induced by the release of these products into the natural environment. However, the "green nanoparticles" and/or "eco-friendly nanoparticles" label does not ensure that biosynthesized NPs are harmless to non-target organisms. Thus, we aimed to synthesize AuNPs from seaweed Gracilaria crassa aqueous extract through an eco-friendly, fast, one-pot synthetic route. The formation of spherical, stable, polycrystalline NPs with a diameter of 32.0 nm ± 4.0 nm (mean ±SEM) was demonstrated by UV-vis spectroscopy, field emission scanning electron microscopy, and high-resolution transmission electron microscopy, energy-dispersive X-ray and X-ray diffraction measurement, and Fourier-transform infrared spectroscopy analysis. In addition, different phytocomponents were identified in the biosynthesized AuNPs, using Gas Chromatography-Mass Spectrometry (GC-MS). However, both G. crassa aqueous extract and the biosynthesized AuNPs showed high ecotoxicity in Anopheles stephensi larvae exposed to different concentrations. Therefore, our study supports the potential of seaweed G. crassa as a raw material source for AuNPs biosynthesis while also shedding light on its ecotoxicological potential, which necessitates consideration of its risk to aquatic biota.

Determinants of Hepatitis B Virus (HBV) Infection Among University Students in Central Bangladesh.

This study aimed to determine the seroprevalence and determinants of hepatitis B virus (HBV) infection among university students in Bangladesh. This cross-sectional study was conducted among 614 students from five universities in central Bangladesh. Data were collected on demographic information, immunization history, medical and blood transfusion history through the face-to-face interview. Blood samples were collected and screened for anti-HBsAg using ELISA, HBsAg Rapid Test-cassette, and immune chromatographic test. The overall seroprevalence of HBV infection was 5.0%, and vaccination coverage was 19.2% among the participants. Students having a history of surgery (OR 11.004, 95% CI 3.211-37.707), blood transfusion (OR 5.651, 95% CI 0.965-33.068), being married (OR 4.776, 95% CI 1.508-15.127), and not being vaccinated (OR 9.825, 95% CI 1.130-85.367) were at higher risk of being infected by HBV. This study showed the endemicity of HBV infection among the Bangladeshi population. Marriage, surgical or blood transfusion history, not being vaccinated were the determinants of HBV infection within the study population. Public health initiatives for preventing HBV infection at the university levels should be envisaged.

Access to female contraceptives by Rohingya refugees, Bangladesh.

OBJECTIVE: To determine the prevalence of the use of contraceptives among female Rohingya refugees in Bangladesh and its associated factors. METHODS: We conducted our cross-sectional survey at the Kutupalong refugee facility located in Cox's Bazar in November 2019. We used univariable and multivariable logistic regression models to determine the association between the use of contraceptives and our various predictor variables, including women's age, age at first marriage, education level and employment status. We also considered factors such as whether previous pregnancies were planned or unplanned, and the occurrence of non-consensual sex with husbands. FINDINGS: We found that 50.91% (251/493) of the survey participants used contraceptives, and that injection (169/251; 67.33%) and oral contraceptives (75/251; 29.88%) were the predominant modes. Of the women who did not use contraceptives, the main reasons were reported as disapproval by husbands (118/242; 48.76%), actively seeking a pregnancy (42/242; 17.36%) and religious beliefs (37/242; 15.29%). An increased likelihood of using contraceptives was found to be positively associated with women's employment outside their households (odds ratio, OR: 3.11; 95% confidence interval, CI: 1.69-6.11) and the presence of a health-care centre in the camp (OR: 3.92; 95% CI: 2.01-7.67). Women who reported an unplanned pregnancy during the previous 2 years were less likely to use contraceptives (OR: 0.02; 95% CI: 0.01-0.05). CONCLUSION: To increase the acceptance and use of contraceptives, we recommend programmes targeted at women of reproductive age and their husbands, religious and community leaders, and providers of family planning and child and maternal health-care services.

COVID-19 pandemic, dengue epidemic, and climate change vulnerability in Bangladesh: Scenario assessment for strategic management and policy implications.

Bangladesh is one of the most vulnerable countries to climate change impacts also struck by the COVID-19 pandemic. The lockdown measures were ineffective with no sign of flattening the curve. Therefore, the high risk of transmission is evident with an increasing number of affected people. Under this circumstance, a multiple hazards scenario can be developed in this country due to climatic hazards such as cyclones, floods, landslides, heat waves, and the outbreak of infectious diseases such as dengue, cholera, and diarrhoea. The country experiences simultaneously the global pandemic, exceptionally prolonged flood along with the recovery stage from the damages due to the cyclone (Amphan). Therefore, these multiple factors have been putting pressure on losing millions of homes, livelihoods, and agricultural crops. This study aimed to assess the potential impact of a simultaneous strike of climatic hazards and infectious disease outbreaks and their possible strategic management in Bangladesh under different scenarios. A mixed methodological approach was followed in this study including a questionnaire survey, in-depth discussion with experts, and extensive literature review to assess the multi-hazard scenario in a resource-limited setting with high population density. A set of statistical techniques were used to analyze the responses (n = 1590) from different social groups (healthcare professionals, academicians, students, Government and NGO officials, and businessman) under three scenarios. The results revealed the high possibility of aggravating the impact of COVID-19 pandemic if there is a climatic hazard such as flood, cyclone have appeared. The majority of the respondents agreed that the situation will become more devastating if there is another outbreak of diseases such as dengue, cholera, and diarrhoea. The poor and fragile healthcare system of this country cannot bear such unprecedented pressure. The lack of risk assessment and communication, lack of sectoral coordination might restrict the contingency plan of the government. Therefore, considering the unprecedented worst cases a stringent strategic plan for emergency response, short term and long-term management should have to be formulated. Resilience building through proactive planning and implementation of integrated, inclusive and sustainable strategies will be effective to ensure the health and socio-economic security for multi-hazard threats in the country.

Allogeneic Platelet-Rich Plasma: Is It Safe and Effective for Wound Repair?

BACKGROUND: Platelet-rich plasma (PRP) and its derivatives are an emerging biotechnology whereby concentrated platelets provide damaged tissue with growth factors, cytokines, and other mediators to improve healing outcomes. Although there is strong evidence in the benefits of autologous PRP for both acute and chronic wounds, allogeneic PRP has been studied far less in comparison. SUMMARY: In this mini-review, we discuss critical steps of allogenic PRP (and its derivatives) preparation. We performed a non-systematic review of the literature to identify animal and human subject studies testing allogenic PRP for wound treatment. We searched OVID Medline and PubMed for articles using the keywords "wound, ulcer, lesion, skin, and cutaneous" and "PRP, or platelet-rich plasma, or platelet-rich fibrin, or PRF, or platelet releasate" and "homologous, allogeneic or allogenic," which were limited to non-review articles and English language. Two studies in animal models and 8 studies in patients were reviewed. There were inconsistencies in preparation methods, treatment regimens, and some lacked a control group in their studies. Despite these variations, none of the studies identified any major side effects or adverse events. The treatment resulted in a reduced time to heal and/or reduced wound size in most cases. Key Messages: In situations where autologous PRP is not available or suitable, allogeneic PRP appears to provide a safe alternative. Its efficacy, however, requires larger-scale studies with appropriate controls. Standardization in PRP preparation and treatment regime are also needed to be able to interpret allogenic PRP efficacy.

Selenium modulates inorganic mercury induced cytotoxicity and intrinsic apoptosis in PC12 cells.

Mercury (Hg) in its all forms, including inorganic Hg (iHg) is an environmental contaminant due to toxicity and diseases in human. However, a little is known about the underlying mechanisms responsible for iHg toxicity. Selenium (Se) is an essential trace element, recognized as an antioxidant and protective agent against metal toxicities. The purpose of this research was to investigate ameliorations of Se counter to iHg-mediated toxicity in PC12 cells. Cytotoxic assays have been shown that iHg (5 µM) caused oxidative stress and intrinsic apoptosis via ROS generation, oxidizing glutathione, damaging DNA, degrading cell membrane integrity, down-regulating mTOR, p-mTOR, akt and ERK1, and up-regulating cleaved caspase 3 and cytochrome c release in PC12 cells 48 h after incubation. Co-treatment of Se (5 µM) inhibited intrinsic apoptosis and oxidative stress induced by iHg (5 µM) via inhibiting ROS formation, boosting GPx contents, increasing reduced glutathione, limiting DNA degradation, improving cell membrane integrity, up-regulating mTOR, p-mTOR, akt, ERK1 and caspase 3, and down-regulating cleaved caspase 3 and cytochrome c leakage in PC12 cells. In conclusion, these results recommended that excessive ROS generation acts a critical role in iHg-influenced oxidative stress and co-treatment of Se attenuates iHg-cytotoxicity through its antioxidant properties.

Exploring the triggering factors for mental stress of university students amid COVID-19 in Bangladesh: A perception-based study.

After the emergence of the COVID-19 pandemic in Bangladesh, the Government decided for lockdown over two months lasting until 30 May 2020. All the universities, along with other educational institutions, are closed down until 19 December 2020. Such measures, however, have the potential to cause and exacerbate the mental stress in people, especially the students. The study aimed to explore the triggering factors which increase the mental stress of the students of both public and private universities amid COVID-19 pandemic. To that end, 1000 students of different public and private universities of the country were surveyed online. Under this study, a quantitative approach was undertaken to infer information from relevant variables through the use of descriptive analysis. Moreover, several virtual Key Informant Interview (KII) sessions were conducted with university teachers, education scholars and psychosocial counselor to get expert views on an effective education system, safeguard of the students and suggestions to reduce the stress of them. The survey result shows that students of private universities (80.6%) were found more mentally stressed than students of public universities (77%). Students of public universities were particularly stressed because of financial crisis and looming university session jam whereas, students of private universities were mentally stressed because of uncertainties of online classes/or activities and high tuition fees. Therefore, it is indispensable to bring in time-oriented policy and plan for the management of education system as well as safeguard of the students amid this pandemic and implement with strong monitoring may decrease the mental stress of them.

Strategic assessment of COVID-19 pandemic in Bangladesh: comparative lockdown scenario analysis, public perception, and management for sustainability.

ABSTRACT: Community transmission of COVID-19 is happening in Bangladesh-the country which did not have a noteworthy health policy and legislative structures to combat a pandemic like COVID-19. Early strategic planning and groundwork for evolving and established challenges are crucial to assemble resources and react in an appropriate timely manner. This article, therefore, focuses on the public perception of comparative lockdown scenario analysis and how they may affect the sustainable development goals (SDGs) and the strategic management regime of COVID-19 pandemic in Bangladesh socio-economically as well as the implications of the withdrawal of partial lockdown plan. Scenario-based public perceptions were collected via a purposive sampling survey method through a questionnaire. Datasets were analysed through a set of statistical techniques including classical test theory, principal component analysis, hierarchical cluster analysis, Pearson's correlation matrix and linear regression analysis. There were good associations among the lockdown scenarios and response strategies to be formulated. Scenario 1 describes how the death and infection rate will increase if the Bangladesh Government withdraws the existing partial lockdown. Scenario 2 outlines that limited people's movement will enable low-level community transmission of COVID-19 with the infection and death rate will increase slowly (r = 0.540, p < 0.01). Moreover, there will be less supply of necessities of daily use with a price hike (r = 0.680, p < 0.01). In scenario 3, full lockdown will reduce community transmission and death from COVID-19 (r = 0.545, p < 0.01). However, along with the other problems gender discrimination and gender-based violence will increase rapidly (r = 0.661, p < 0.01). Due to full lockdown, the formal and informal business, economy, and education sector will be hampered severely (R = 0.695). Subsequently, there was a strong association between the loss of livelihood and the unemployment rate which will increase due to business shutdown (p < 0.01). This will lead to the severe sufferings of poor and vulnerable communities in both urban and rural areas (p < 0.01). All these will further aggravate the humanitarian needs of the most vulnerable groups in the country in the coming months to be followed which will undoubtedly affect the Bangladesh targets to achieve the SDGs of 2030 and other development plans that need to be adjusted. From our analysis, it was apparent that maintaining partial lockdown with business and economic activities with social distancing and public health guidelines is the best strategy to maintain. However, as the government withdrew the partial lockdown, inclusive and transparent risk communication towards the public should be followed. Recovery and strengthening of the health sector, economy, industry, agriculture, and food security should be focused on under the "new normal standard of life" following health guidelines and social distancing. Proper response plans and strategic management are necessary for the sustainability of the nation.

Genetic polymorphisms in DNA repair genes XRCC1 and 3 are associated with increased risk of breast cancer in Bangladeshi population.

BACKGROUND: Genetic polymorphisms in DNA repair genes, XRCC1 (Arg399Gln) and XRCC3 (Thr241Met), may affect their DNA repair capacity leading to individual variation in breast cancer susceptibility among Bangladeshi females. METHODS: The case-control study comprised 121 breast cancer patients and 133 healthy controls. Genomic DNA isolated from peripheral blood was genotyped for target SNPs using PCR-RFLP method. RESULTS: For XRCC1, heterozygous Arg/Gln and homozygous Gln/Gln genotypes showed 1.78-fold (95% CI 1.0084 to 3.1442, p = 0.0467) and 2.41-fold (95% CI 1.0354 to 5.5914, p = 0.0413) increased risk of breast cancer, respectively, when compared with Arg/Arg genotype. The presence of any XRCC1 Gln showed association with 1.93-fold increased risk. The variant Gln allele was associated with increased risk of breast cancer (95% CI 1.1885 to 2.6805, p = 0.0052). For XRCC3, Thr/Met heterozygous and combined Thr/Met + Met/Met genotypes were associated with 1.85-fold (95% CI 1.0815 to 3.1834, p = 0.0248) and 1.89-fold (95% CI 1.1199 to 3.1908, p = 0.0171) higher risk, respectively, compared to Thr/Thr genotypes. The variant Met allele showed significant association with increased breast cancer susceptibility. Among cases genotype frequencies were significantly different in patients with age 55 or above, and with menopause and diabetes. CONCLUSION: XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) polymorphisms may be associated with increased breast cancer risk in Bangladeshi females.

Depleted uranium and Gulf War Illness: Updates and comments on possible mechanisms behind the syndrome.

Indications of proximal tubule effects have been observed in recent surveillance study of Gulf War veterans exposed to depleted uranium (DU). This gives some support for the suspicion that DU may represent one of the causes for the so-called Persian Gulf syndrome. Proposed effects may be especially harmful if the toxicity hits the mitochondrial DNA since the mitochondria lack the nucleotide excision repair mechanism, which is needed for repairing bulky adducts that have been associated with DU. It is a plausible working hypothesis that a significant part of the symptoms from various organs, which have been observed among veterans from Gulf War 1 and that have been grouped under the name of the Persian Gulf syndrome, may be explained as a consequence of mitochondrial DNA damage in various cell types and organs. Interpretation of observations, on military personnel and civilians after Gulf War 1, is associated with difficulties because of the abundance of potential confounding factors. The symptoms observed on veterans from Gulf War 1 may be attributed to a multiplicity of substances functioning directly or indirectly as mitochondrial mutagens. A concise analysis of the cascade of toxic effects initiated by DU exposure in the human body is the subject of this article.

Uranium in drinking water: a public health threat.

Uranium (U) has no known essential biological functions. Furthermore, it is well known for its toxicity, radioactivity, and carcinogenic potency. Impacts on human health due to U exposure have been studied extensively by many researchers. Chronic exposure to low-level U isotopes (radionuclides) may be interlinked with cancer etiology and at high exposure levels, also kidney disease. Other important issues covered U and fertilizers, and also U in soils or human tissues as an easily measurable indicator element in a pathophysiological examination. Furthermore, phosphate fertilization is known as the important source of contamination with U in the agricultural land, mainly due to contamination in the phosphate rock applied for fertilizer manufacture. Therefore, long-term usage of U-bearing fertilizers can substantially increase the concentration of U in fertilized soils. It should also be noted that U is an active redox catalyst for the reaction between DNA and H2O2. This review is aimed to highlight a series on various hydro-geochemical aspects in different water sources and focused on the comparison of different U contents in the drinking water sources and presentation of data in relation to health issues.

Regulatory effects of dihydrolipoic acid against inorganic mercury-mediated cytotoxicity and intrinsic apoptosis in PC12 cells.

Mercury (Hg) is an extremely dangerous environmental contaminant, responsible for human diseases including neurological disorders. However, the mechanisms of inorganic Hg (iHg)-induced cell death and toxicity are little known. Dihydrolipoic acid (DHLA) is the reduced form of a naturally occurring compound lipoic acid, which act as a potent antioxidant through multiple mechanisms. So we hypothesized that DHLA has an inhibitory role on iHg-cytotoxicity. The purposes of this research were to investigate mechanism/s of cytotoxicity of iHg, as well as, the cyto-protection of DHLA against iHg induced toxicity using PC12 cells. Treatment of PC12 cells with HgCl2 (Hg2+) (0-2.5 µM) for 48 h resulted in significant toxic effects, such as, cell viability loss, high level of lactate dehydrogenase (LDH) release, DNA damage, cellular glutathione (GSH) level decrease and increased Hg accumulation. In addition, protein level expressions of akt, p-akt, mTOR, GR, NFkB, ERK1, Nrf2 and HO-1 in cells were downregulated; and cleaved caspase 3 and cytochrome c release were upregulated after Hg2+ (2.5 µM) exposure and thus inducing apoptosis. Hg2+induced apoptosis was also confirmed by flow cytometry. However, pretreatment with DHLA (50 µM) for 3 h before Hg2+ (2.5 µM) exposure showed inhibition against iHg2+-induced cytotoxicity by reversing cell viability loss, LDH release, DNA damage, GSH decrease and inhibiting Hg accumulation. Moreover, DHLA pretreatment reversed the protein level expressions of akt, p-akt, mTOR, GR, NFkB, ERK1, Nrf2, HO-1, cleaved caspase 3 and cytochrome c. In conclusion, results showed that DHLA could attenuate Hg2+-induced cytotoxicity via limiting Hg accumulation, boosting up of antioxidant defense, and inhibition of apoptosis in cells.

Curcumin alleviates arsenic-induced toxicity in PC12 cells via modulating autophagy/apoptosis.

Arsenic is a recognized highly toxic contaminant, responsible for numerous human diseases and affecting many millions of people in different parts of the world. Contrarily, curcumin is a natural dietary polyphenolic compound and the main active ingredient in turmeric. Recently it has drawn great attention due to its diverse biological activities, strong antioxidant properties and therapeutic potential against many human ailments. In this study, we aimed to explore the protective effects and the regulatory role of curcumin on arsenic-induced toxicity and gain insights into biomolecular mechanism/s. Arsenic (10 µM) treatment in PC12 cells for 24 h induced cytotoxicity by decreasing cell viability and intracellular glutathione level and increasing lactate dehydrogenase activity and DNA fragmentation. In addition, arsenic caused apoptotic cell death in PC12 cells, which were confirmed from flow cytometry results. Moreover, arsenic (10 µM) treatment significantly down-regulated the inhibition factors of autophagy/apoptosis; mTOR, Akt, Nrf2, ERK1, Bcl-x, Xiap protein expressions, up-regulated the enhanced factors of autophagy/apoptosis; ULK, LC3, p53, Bax, cytochrome c, caspase 9, cleaved caspase 3 proteins and eventually caused autophagic and apoptotic cell death. However, curcumin (2.5 µM) pretreatment with arsenic (10 µM) effectively saves PC12 cells against arsenic-induced cytotoxicity through increasing cell viability, intracellular GSH level and boosting the antioxidant defense system, and limiting the LDH activity and DNA damage. Furthermore, pretreatment of curcumin with arsenic expressively alleviated arsenic-induced toxicity and cell death by reversing the expressions of proteins; mTOR, Akt, Nrf2, ERK1, Bcl-x, Xiap, ULK, LC3, p53, Bax, cytochrome c, caspase 9 and cleaved caspase 3. Our findings indicated that curcumin showed antioxidant properties through the Nrf2 antioxidant signaling pathway and alleviates arsenic-triggered toxicity in PC12 cells by regulating autophagy/apoptosis.