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Acne vulgaris (AV) is a psychosomatic disorder and can negatively affect individuals, especially in terms of psychological well-being, self-esteem, and quality of life (QoL). The current study aimed to investigate the association between AV and psychological health, as well as the influence of acne and psychological distress in predicting patients' self-esteem and QoL. This cross-sectional study included 150 patients clinically diagnosed with AV. The severity of acne was measured using GAGS, and following that, patients were instructed to complete the following forms: DASS-21, RSES, CADI, DLQI, and WHOQoL. Female AV patients had significantly higher depression (p = 0.003, t = 3.025) and anxiety (p < 0.001, t = 3.683). Pearson's correlation analysis indicated a strong, positive, and significant correlation between having acne and experiencing depression (r = 0.630), anxiety (r = 0.661), and stress (r = 0.758) (p < 0.001). Multiple regression analysis suggested acne and associated psychological distress had a significant and negative impact on the patient's self-esteem and quality of life. This study highlights the multifaceted consequences of AV and the need to manage its psychological distress. It emphasizes the need for holistic patient care that addresses acne's physical and emotional aspects, with the ultimate goal of enhancing well-being and QoL., (© 2023. The Author(s).)

Diabetes mellitus, a chronic metabolic disorder characterized by hyperglycemia, presents a formidable global health challenge with its associated complications. Adiponectin, an adipocyte-derived hormone, has emerged as a significant player in glucose metabolism and insulin sensitivity. Beyond its metabolic effects, adiponectin exerts anti-inflammatory, anti-oxidative, and vasoprotective properties, making it an appealing therapeutic target for mitigating diabetic complications. The molecular mechanisms by which adiponectin impacts critical pathways implicated in diabetic nephropathy, retinopathy, neuropathy, and cardiovascular problems are thoroughly examined in this study. In addition, we explore possible treatment options for increasing adiponectin levels or improving its downstream signaling. The multifaceted protective roles of adiponectin in diabetic complications suggest its potential as a novel therapeutic avenue. However, further translational studies and clinical trials are warranted to fully harness the therapeutic potential of adiponectin in the management of diabetic complications. This review highlights adiponectin as a promising target for the treatment of diverse diabetic complications and encourages continued research in this pivotal area of diabetes therapeutics.

Clostridium butyricum is known as a probiotic butyric acid bacterium that can improve the intestinal environment. In this study, we isolated a new strain of C. butyricum from infant feces and evaluated its physiological characteristics and antiviral efficacy by modulating the innate immune responses in vitro and in vivo . The isolated C. butyricum S-45-5 showed typical characteristics of C. butyricum including bile acid resistance, antibacterial ability, and growth promotion of various lactic acid bacteria. As an antiviral effect, C. butyricum S-45-5 markedly reduced the replication of influenza A virus (PR8), Newcastle Disease Virus (NDV), and Herpes Simplex Virus (HSV) in RAW264.7 cells in vitro . This suppression can be explained by the induction of antiviral state in cells by the induction of antiviral, IFN-related genes and secretion of IFNs and pro-inflammatory cytokines. In vivo , oral administration of C. butyricum S-45-5 exhibited prophylactic effects on BALB/c mice against fatal doses of highly pathogenic mouse-adapted influenza A subtypes (H1N1, H3N2, and H9N2). Before challenge with influenza virus, C. butyricum S-45-5-treated BALB/c mice showed increased levels of IFN-β, IFN-γ, IL-6, and IL-12 in serum, the small intestine, and bronchoalveolar lavage fluid (BALF), which correlated with observed prophylactic effects. Interestingly, after challenge with influenza virus, C. butyricum S-45-5-treated BALB/c mice showed reduced levels of pro-inflammatory cytokines and relatively higher levels of anti-inflammatory cytokines at day 7 post-infection. Taken together, these findings suggest that C. butyricum S-45-5 plays an antiviral role in vitro and in vivo by inducing an antiviral state and affects immune modulation to alleviate local and systemic inflammatory responses caused by influenza virus infection. Our study provides the beneficial effects of the new C. butyricum S-45-5 with antiviral effects as a probiotic., Competing Interests: Author HK is employed by the company Vitabio, Inc., Daejeon, Republic of Korea. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chathuranga, Shin, Uddin, Paek, Chathuranga, Seong, Bai, Kim, Shin, Chang and Lee.)

Introduction: A frequent sequela of influenza A virus (IAV) infection is secondary bacterial pneumonia. Therefore, it is clinically important to understand the genetic predisposition to IAV and bacterial coinfection., Methods: BALB/c and C57BL/6 (B6) mice were infected with high or low-pathogenic IAV and Streptococcus pneumoniae ( SPn ). The contribution of cellular and molecular immune factors to the resistance/susceptibility of BALB/c and B6 mice were dissected in nonlethal and lethal IAV/ SPn coinfection models., Results: Low-virulent IAV X31 (H3N2) rendered B6 mice extremely susceptible to SPn superinfection, while BALB/c mice remained unaffected. X31 infection alone barely induces IFN-γresponse in two strains of mice; however, SPn superinfection significantly enhances IFN-γ production in the susceptible B6 mice. As a result, IFN-γ signaling inhibits neutrophil recruitment and bacterial clearance, leading to lethal X31/ SPn coinfection in B6 mice. Conversely, the diminished IFN-γ and competent neutrophil responses enable BALB/c mice highly resistant to X31/SPn coinfection., Discussion: The results establish that type 1 immune predisposition plays a key role in lethal susceptibility of B6 mice to pneumococcal pneumonia after mild IAV infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Palani, Uddin, McKelvey, Shao and Sun.)

The dysregulated phosphatidylinositol-3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) signaling pathway has been implicated in various immune-mediated inflammatory and hyperproliferative dermatoses such as acne, atopic dermatitis, alopecia, psoriasis, wounds, and vitiligo, and is associated with poor treatment outcomes. Improved comprehension of the consequences of the dysregulated PI3K/Akt/mTOR pathway in patients with inflammatory dermatoses has resulted in the development of novel therapeutic approaches. Nonetheless, more studies are necessary to validate the regulatory role of this pathway and to create more effective preventive and treatment methods for a wide range of inflammatory skin diseases. Several studies have revealed that certain natural products and synthetic compounds can obstruct the expression/activity of PI3K/Akt/mTOR, underscoring their potential in managing common and persistent skin inflammatory disorders. This review summarizes recent advances in understanding the role of the activated PI3K/Akt/mTOR pathway and associated components in immune-mediated inflammatory dermatoses and discusses the potential of bioactive natural products, synthetic scaffolds, and biologic agents in their prevention and treatment. However, further research is necessary to validate the regulatory role of this pathway and develop more effective therapies for inflammatory skin disorders.

Plastic, in all its forms, always harms the environment, humans, and other living organisms. The coronavirus situation exacerbates the use of plastic products more than at any other time, of which surgical masks contribute to plastic pollution the most. These masks spread to terrestrial and aquatic environments, where they break down into even more noxious microplastics. These microplastics enter the human food chain through water and fish, causing severe damage to the lungs, kidneys, and intestines and even causing death. In this paper, a jute nose holder mask was prepared as an alternative to typical masks to reduce plastic pollution. The jute nose holder was produced with a modified jute flyer-spinning frame machine, where jute was used as the sheath and metal wire was applied as the core component. The nose holder was later coated with starch-based natural gum. Then, the non-woven fabric of 75 grams per square meter (GSM), and the jute nose holder were used to produce the alternative, environmentally friendly mask, which might reduce the 773 tons of plastic waste generated daily from the nose holder of the mask. This alternative mask was then distributed to 900 people for a survey to find out their opinion. From the results of the survey, it is seen that 82.6% of people felt no problem in the nose when they put on the given mask. 85.6% considered the mask more comfortable than the traditional mask, and it was rated above average by 79.8% of the surveyors. So, this study suggests that the given mask can be a sustainable alternative to traditional masks., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background Venous thromboembolism (VTE) is quite common among post-operative neurosurgical patients. This study aims to identify the incidence of deep vein thrombosis (DVT) and superficial vein thrombosis (SVT) among post-craniotomy/craniectomy patients and further evaluate established hypercoagulability risk factors such as trauma, tumors, and surgery. Methodology This single-center retrospective study investigated 197 patients who underwent a craniotomy/craniectomy. The incidences of DVT and SVT were compared, along with laterality and peripherally inserted central catheter (PICC) line involvement. A multivariate logistic regression analysis was conducted to identify risk factors for post-craniotomy/craniectomy VTE. This model included variables such as age, post-operative days before anticoagulant administration, female sex, indications for surgery such as tumor and trauma, presence of a PICC line, and anticoagulant administration. Results Among the 197 post-craniotomy/craniectomy patients (39.6% female; mean age 53.8±15.7 years), the incidences of DVT, SVT, and VTE were 4.6%, 9.6%, and 12.2%, respectively. The multivariate logistic regression analysis found that increasing the number of days between surgery and administration of anticoagulants significantly increased the risk of VTE incidence (odds ratio 1.183, 95% CI 1.068-1.311, p = 0.001). Conclusions Contrary to existing evidence, this study did not find trauma or the presence of tumors to be risk factors for VTE. Future prospective studies should assess VTE risk assessment models such as "3 Bucket" or "Caprini" to develop universal guidelines for administering anticoagulant therapy to post-craniotomy/craniectomy patients that consider the timing of post-operative therapy initiation., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Gupta et al.)

Immunomodulatory (IM) metabolic reprogramming in macrophages (Mϕs) is fundamental to immune function. However, limited information is available for human Mϕs, particularly in response plasticity, which is critical to understanding the variable efficacy of immunotherapies in cancer patients. We carried out an in-depth analysis by combining multiplex stable isotope-resolved metabolomics with reversed phase protein array to map the dynamic changes of the IM metabolic network and key protein regulators in four human donors' Mϕs in response to differential polarization and M1 repolarizer β-glucan (whole glucan particles [WGPs]). These responses were compared with those of WGP-treated ex vivo organotypic tissue cultures (OTCs) of human non-small cell lung cancer. We found consistently enhanced tryptophan catabolism with blocked NAD + and UTP synthesis in M1-type Mϕs (M1-Mϕs), which was associated with immune activation evidenced by increased release of IL-1β/CXCL10/IFN-γ/TNF-α and reduced phagocytosis. In M2a-Mϕs, WGP treatment of M2a-Mϕs robustly increased glucose utilization via the glycolysis/oxidative branch of the pentose phosphate pathway while enhancing UDP- N -acetyl-glucosamine turnover and glutamine-fueled gluconeogenesis, which was accompanied by the release of proinflammatory IL-1β/TNF-α to above M1-Mϕ's levels, anti-inflammatory IL-10 to above M2a-Mϕ's levels, and attenuated phagocytosis. These IM metabolic responses could underlie the opposing effects of WGP, i.e., reverting M2- to M1-type immune functions but also boosting anti-inflammation. Variable reprogrammed Krebs cycle and glutamine-fueled synthesis of UTP in WGP-treated OTCs of human non-small cell lung cancer were observed, reflecting variable M1 repolarization of tumor-associated Mϕs. This was supported by correlation with IL-1β/TNF-α release and compromised tumor status, making patient-derived OTCs unique models for studying variable immunotherapeutic efficacy in cancer patients., (Copyright © 2022 by The American Association of Immunologists, Inc.)

Lumpy skin disease (LSD) is a fulminant infectious disease that mostly affects cattle and causes considerable economic loss throughout the globe. This study was conducted to develop a new multi-epitope-based vaccine against LSD that can elicit immunological responses using an in silico reverse vaccinology approach. Initially, three antigenic proteins, protein E5, E3 ubiquitin-protein ligase LAP and 62 kDa protein, were manipulated to recognize potential T-cell and B-cell epitopes. To identify superior epitopes, a variety of bioinformatic techniques including antigenicity testing, transmembrane topology screening, allergenicity assessment, conservancy analysis, and toxicity evaluation were used. Finally, three new subunit vaccines (construct V1, V2 and V3) were developed employing the most effective epitopes, suitable adjuvants, pan HLA DR-binding epitope (PADRE) and linkers. Then, based on the antigenicity, solubility, and validation score of the 3D structures, construct V2 was chosen as one of the best candidate vaccines. The results of the molecular dynamic simulation and disulphide engineering indicated that the vaccine (construct V2) was stable. Additionally, the immunological simulation findings supported the vaccine candidate's ability to trigger humoral and cellular immune responses. Further validation of the proposed vaccine candidate may necessitate additional in vitro and in vivo investigations., (© 2022 Wiley-VCH GmbH.)

Multiple organ damage is common in patients with severe COVID-19, even though the underlying pathogenic mechanisms remain unclear. Acute viral infection typically activates type I IFN (IFN-I) signaling. The antiviral role of IFN-I is well characterized in vitro. However, our understanding of how IFN-I regulates host immune response to SARS-CoV-2 infection in vivo is incomplete. Using a human ACE2-transgenic mouse model, we show in the present study that IFN-I receptor signaling is essential for protection against the acute lethality of SARS-CoV-2 in mice. Interestingly, although IFN-I signaling limits viral replication in the lung, the primary infection site, it is dispensable for efficient viral clearance at the adaptive phase of SARS-CoV-2 infection. Conversely, we found that in the absence of IFN-I receptor signaling, the extreme animal lethality is consistent with heightened infectious virus and prominent pathological manifestations in the brain. Taken together, our results in this study demonstrate that IFN-I receptor signaling is required for restricting virus neuroinvasion, thereby mitigating COVID-19 severity., (Copyright © 2022 The Authors.)

Foot-and-mouth disease virus (FMDV) is a single-stranded, positive-sense RNA virus containing at least 13 proteins. Many of these proteins show immune modulation capabilities. As a non-structural protein of the FMDV, 2B is involved in the rearrangement of the host cell membranes and the disruption of the host secretory pathway as a viroporin. Previous studies have also shown that FMDV 2B plays a role in the modulation of host type-I interferon (IFN) responses through the inhibition of expression of RIG-I and MDA5, key cytosolic sensors of the type-I IFN signaling. However, the exact molecular mechanism is poorly understood. Here, we demonstrated that FMDV 2B modulates host IFN signal pathway by the degradation of RIG-I and MDA5. FMDV 2B targeted the RIG-I for ubiquitination and proteasomal degradation by recruiting E3 ubiquitin ligase ring finger protein 125 (RNF125) and also targeted MDA5 for apoptosis-induced caspase-3- and caspase-8-dependent degradation. Ultimately, FMDV 2B significantly inhibited RNA virus-induced IFN-β production. Importantly, we identified that the C-terminal amino acids 126-154 of FMDV 2B are essential for 2B-mediated degradation of the RIG-I and MDA5. Collectively, these results provide a clearer understanding of the specific molecular mechanisms used by FMDV 2B to inhibit the IFN responses and a rational approach to virus attenuation for future vaccine development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Weerawardhana, Uddin, Choi, Pathinayake, Shin, Chathuranga, Park and Lee.)

Acute Respiratory Distress Syndrome (ARDS) is an inflammatory disease that is associated with high mortality but no specific treatment. Our understanding of initial events that trigger ARDS pathogenesis is limited. We have developed a mouse model of inflammatory lung injury by influenza and methicillin-resistant Staphylococcus aureus (MRSA) coinfection plus daily antibiotic therapy. Using this pneumonic ARDS model, here we show that IFN-γ receptor signaling drives inflammatory cytokine storm and lung tissue damage. By single-cell RNA sequencing (scRNA-seq) analysis, we demonstrate that IFN-γ signaling induces a transcriptional shift in airway immune cells, particularly by upregulating macrophage and monocyte expression of genes associated with inflammatory diseases. Further evidence from conditional knockout mouse models reveals that IFN-γ receptor signaling in myeloid cells, particularly CD11c + mononuclear phagocytes, directly promotes TNF-α hyperproduction and inflammatory lung damage. Collectively, the findings from this study, ranging from cell-intrinsic gene expression to overall disease outcome, demonstrate that influenza-induced IFN-γ triggers myeloid cell hyperresponsiveness to MRSA, thereby leading to excessive inflammatory response and lethal lung damage during coinfection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Verma, McKelvey, Uddin, Palani, Niu, Bauer, Shao and Sun.)

Background: Glucagon-like peptide-1 (GLP1) is an endogenous peptide that regulates blood glucose level. But its susceptibility to rapid metabolic degradation limits its therapeutic use., Aim: To prepare GLP1-encapsulated nanosize particle with controlled release property to improve the systemic half-life of GLP1., Methods: GLP1 nanoparticles were prepared by complexation of GLP1 with carbonate apatite nanoparticles (CA NPs). The physicochemical properties of the CA NPs, the effects of GLP1-loaded CA NPs on cell viability, and the systemic bioavailability of GLP1 after CA NPs administration were determined., Results: The GLP1-loaded CA NPs was within 200 nm in size and stable in fetal bovine serum. The formulation did not affect the viability of human cell lines suggesting that the accumulation of CA NPs in target tissues is safe. In Sprague Dawley rats, the plasma GLP1 Levels as measured from the GLP1-loaded CA NPs-treated rats, were significantly higher than that of the control rats and free GLP1-treated rats at 1 h post-treatment ( P < 0.05), and the level remained higher than the other two groups for at least 4 h., Conclusion: The GLP1-loaded CA NPs improved the plasma half-life of GLP1. The systemic bioavailability of GLP1 is longer than other GLP1 nanoparticles reported to date., Competing Interests: Conflict-of-interest statement: There is no conflict-of-interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Cancer cells acquire immunoediting ability to evade immune surveillance and thus escape eradication. It is widely known that mutant proteins encoded from tumor suppressor TP53 exhibit gain-of-function in cancer cells, thereby promoting progression; however, how mutant p53 contributes to the sheltering of cancer cells from host anticancer immunity remains unclear. Herein, we report that murine p53 missense mutation G242A (corresponding to human G245A) suppresses the activation of host natural killer (NK) cells, thereby enabling breast cancer cells to avoid immune assault. We found that serial injection of EMT6 breast cancer cells that carry wild-type (wt) Trp53, like normal fibroblasts, promoted NK activity in mice, while SVTneg2 cells carrying Trp53 G242A +/+ mutation decreased NK cell numbers and increased CD8 + T lymphocyte numbers in spleen. Innate immunity based on NK cells and CD8 T cells was reduced in p53 mutant-carrying transgenic mice (Trp53 R172H /+ , corresponding to human R175H /+ ). Further, upon co-culture with isolated NK cells, EMT6 cells substantively activated NK cells and proliferation thereof, increasing interferon-gamma (IFN-γ) production; however, SVTneg2 cells suppressed NK cell activation. Further mechanistic study elucidated that p53 can modulate expression by cancer cells of Mult-1 and H60a, which are activating and inhibitory ligands for NKG2D receptors of NK cells, respectively, to enhance immune surveillance against cancer. Our findings demonstrate that wt p53 is requisite for NK cell-based immune recognition and elimination of cancerous cells, and perhaps more importantly, that p53 missense mutant presence in cancer cells impairs NK cell-attributable responses, thus veiling cancerous cells from host immunity and enabling cancer progression., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Research on the immune system and cancer has led to the development of new medicines that enable the former to attack cancer cells. Drugs that specifically target and destroy cancer cells are on the horizon; there are also drugs that use specific signals to stop cancer cells multiplying. Machine learning algorithms can significantly support and increase the rate of research on complicated diseases to help find new remedies. One area of medical study that could greatly benefit from machine learning algorithms is the exploration of cancer genomes and the discovery of the best treatment protocols for different subtypes of the disease. However, developing a new drug is time-consuming, complicated, dangerous, and costly. Traditional drug production can take up to 15 years, costing over USD 1 billion. Therefore, computer-aided drug design (CADD) has emerged as a powerful and promising technology to develop quicker, cheaper, and more efficient designs. Many new technologies and methods have been introduced to enhance drug development productivity and analytical methodologies, and they have become a crucial part of many drug discovery programs; many scanning programs, for example, use ligand screening and structural virtual screening techniques from hit detection to optimization. In this review, we examined various types of computational methods focusing on anticancer drugs. Machine-based learning in basic and translational cancer research that could reach new levels of personalized medicine marked by speedy and advanced data analysis is still beyond reach. Ending cancer as we know it means ensuring that every patient has access to safe and effective therapies. Recent developments in computational drug discovery technologies have had a large and remarkable impact on the design of anticancer drugs and have also yielded useful insights into the field of cancer therapy. With an emphasis on anticancer medications, we covered the various components of computer-aided drug development in this paper. Transcriptomics, toxicogenomics, functional genomics, and biological networks are only a few examples of the bioinformatics techniques used to forecast anticancer medications and treatment combinations based on multi-omics data. We believe that a general review of the databases that are now available and the computational techniques used today will be beneficial for the creation of new cancer treatment approaches.

Postinfluenza bacterial pneumonia is a significant cause of hospitalization and death in humans. The mechanisms underlying this viral and bacterial synergy remain incompletely understood. Recent evidence indicates that influenza-induced IFNs, particularly type I IFN (IFN-I) and IFN-γ, suppress antibacterial defenses. In this study, we have investigated the relative importance and interplay of IFN-I and IFN-γ pathways in influenza-induced susceptibility to Streptococcus pneumoniae infection. Using gene-deficient mouse models, as well as in vivo blocking Abs, we show that both IFN-I and IFN-γ signaling pathways contribute to the initial suppression of antibacterial immunity; however, IFN-γ plays a dominant role in the disease deterioration, in association with increased TNF-α production and alveolar macrophage (AM) depletion. We have previously shown that IFN-γ impairs AM antibacterial function and thereby acute bacterial clearance. The findings in this study indicate that IFN-γ signaling also impairs AM viability and αβ T cell recruitment during the progression of influenza/ S. pneumoniae coinfection. Macrophages insensitive to IFN-γ mice express a dominant-negative mutant IFN-γR in mononuclear phagocytes. Interestingly, macrophages insensitive to IFN-γ mice exhibited significantly improved recovery and survival from coinfection, despite delayed bacterial clearance. Importantly, we demonstrate that IFN-I receptor signaling is essential for preventing IFN-γ hyperproduction and animal death during the progression of postinfluenza pneumococcal pneumonia., (Copyright © 2022 by The American Association of Immunologists, Inc.)

Objective . Sleep apnea is a common sleep breathing disorder that can significantly decrease sleep quality and have major health consequences. It is diagnosed based on the apnea hypopnea index (AHI). This study explored a novel, generalized algorithm for the automatic diagnosis of sleep apnea employing airflow (AF) and oximetry (SpO 2 ) signals. Approach . Of the 988 polysomnography records, 45 were randomly selected for developing the automatic algorithm and the remainder 943 for validating purposes. The algorithm detects apnea events by a per-sample encoding process applied to the peak excursion of AF signal. Hypopnea events were detected from the per-sample encoding of AF and SpO 2 with an adjustment to time lag in SpO 2 . Total recording time was automatically processed and optimized for computation of total sleep time (TST). Total number of detected events and computed TST were used to estimate AHI. The estimated AHI was validated against the scored data from the Sleep Heart Health Study. Main results . Intraclass correlation coefficient of 0.94 was obtained between estimated and scored AHIs. The diagnostic accuracies were 93.5%, 92.4%, and 96.6% for AHI cut-off values of ≥5, ≥15, and ≥30 respectively. The overall accuracy for the combined severity categories (normal, mild, moderate, and severe) and kappa were 83.4% and 0.77 respectively. Significance . This new automatic technique was found to be superior to the other existing methods and can be applied to any portable sleep devices especially for home sleep apnea tests., (© 2022 Institute of Physics and Engineering in Medicine.)

Hexavalent chromium [Cr(VI)] is a common environmental carcinogen causing lung cancer in humans. This study investigates the mechanism of Cr(VI) carcinogenesis focusing on the role of the epitranscriptomic dysregulation. The epitranscriptomic effect of Cr(VI) was determined in Cr(VI)-transformed human bronchial epithelial cells, chromate-exposed mouse and human lungs. The epitranscriptomic effect and its role in Cr(VI)-induced cell transformation, cancer stem cell (CSC)-like property, and tumorigenesis were determined by microarray analysis, soft agar colony formation, suspension spheroid formation, and mouse xenograft tumorigenesis assays. It was found that chronic Cr(VI) exposure causes epitranscriptomic dysregulations as evidenced by the increased levels of total RNA N6-methyladenosine (m6A) modification and the RNA m6A methyltransferase like-3 (METTL3) in Cr(VI)-transformed cells and chromate exposure-caused mouse and human lung tumors. Knockdown of METTL3 expression in Cr(VI)-transformed cells significantly reduces their m6A levels and transformed phenotypes and tumorigenicity in mice. Moreover, knockdown of METTL3 expression in parental nontransformed cells significantly reduces the capability of chronic Cr(VI) exposure to induce cell transformation and CSC-like property. Together, this study reveals that chronic Cr(VI) exposure is capable of altering cellular epitranscriptome by increasing the m6A RNA modification via upregulating the RNA methyltransferase METTL3 expression, which plays an important role in Cr(VI)-induced cell transformation, CSC-like property, and tumorigenesis., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The hybridization effect of agro-waste pineapple leaf fibre (PALF) and jute fibre as reinforcement in linear low-density polyethylene (LLDPE) composites was investigated in this work. The samples were fabricated by using the heat press compression moulding. The effect of gamma irradiation on composite physico-mechanical properties was also investigated in order to determine the best gamma dose among 2.50, 5.00, 7.50, and 10.00 kGy. The composite sample containing 40% PALF and 60% jute (with a total weight of 50% fibres) demonstrated the most feasible tensile strength (33.36 ± 0.59 MPa), tensile modulus (1494.41 ± 10.94 MPa), elongation at break (50.92 ± 0.77%), bending strength (82.58 ± 0.49 MPa), bending modulus (4932.46 ± 96.12 MPa), and impact strength (34.38 ± 0.42 kJ/m 2 ) at 7.50 kGy irradiation. Thermogravimetric analysis (TGA) determined the thermal performance of the samples. Scanning electron microscopy (SEM) images at the tensile fracture surfaces of composites revealed the interfacial interaction between reinforcement fibres and matrix., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Sexually transmitted infections (STI) symptoms (e.g., abnormal genital discharge and genital sores/ulcers) are a major public health concern in Bangladesh because the symptoms can indicate an STI and cause sexual and reproductive health complications in women of reproductive age. To our knowledge, no study examined the prevalence and risk factors of STI symptoms using a nationally representative sample. This study investigates the prevalence of STI symptoms among ever-married women in Bangladesh and the associations of STI symptoms with various demographic, socioeconomic, and behavioral risk factors using the most recent available data (2007, 2011, and 2014) of the Bangladesh Demographic and Health Surveys (BDHS). The BDHS employs a two-stage stratified sampling technique. The analytic sample comprised 41,777 women of reproductive age (15-49 years). Outcome variables included STI symptoms: abnormal genital discharge and genital sores/ulcers. Multivariate logistic regression was employed to find the adjusted odds ratio with a 95% confidence interval to assess the associations of outcome measures with explanatory variables. The study found that the prevalence of abnormal genital discharge and genital sores/ulcers among ever-married women aged 15-49 years was 10% and 6%, respectively. Multivariable analysis revealed that for women aged 25-34 years, those who used contraceptives and married earlier had an increased likelihood of STI symptoms. Furthermore, women from the wealthiest wealth quintile and couple's joint decision-making were less likely to have STI symptoms. Findings have implications for interventions efforts aiming to improve women's sexual and reproductive health in Bangladesh.

Neurodegenerative diseases are a global health issue with inadequate therapeutic options and an inability to restore the damaged nervous system. With advances in technology, health scientists continue to identify new approaches to the treatment of neurodegenerative diseases. Lost or injured neurons and glial cells can lead to the development of several neurological diseases, including Parkinson's disease, stroke, and multiple sclerosis. In recent years, neurons and glial cells have successfully been generated from stem cells in the laboratory utilizing cell culture technologies, fueling efforts to develop stem cell-based transplantation therapies for human patients. When a stem cell divides, each new cell has the potential to either remain a stem cell or differentiate into a germ cell with specialized characteristics, such as muscle cells, red blood cells, or brain cells. Although several obstacles remain before stem cells can be used for clinical applications, including some potential disadvantages that must be overcome, this cellular development represents a potential pathway through which patients may eventually achieve the ability to live more normal lives. In this review, we summarize the stem cell-based therapies that have been explored for various neurological disorders, discuss the potential advantages and drawbacks of these therapies, and examine future directions for this field.

The susceptibility to respiratory syncytial virus (RSV) infection in early life has been associated with a deficient T-helper cell type 1 (Th1) response. Conversely, healthy adults generally do not exhibit severe illness from RSV infection. In the current study, we investigated whether Th1 cytokine IFN-γ is essential for protection against RSV and RSV-associated comorbidities in adult mice. We found that, distinct from influenza virus, prior RSV infection does not induce significant IFN-γ production and susceptibility to secondary Streptococcus pneumoniae infection in adult wild-type (WT) mice. In ovalbumin (OVA)-induced asthmatic mice, RSV super-infection increases airway neutrophil recruitment and inflammatory lung damage but has no significant effect on OVA-induced eosinophilia. Compared with WT controls, RSV infection of asthmatic Ifng -/- mice results in increased airway eosinophil accumulation. However, a comparable increase in eosinophilia was detected in house dust mite (HDM)-induced asthmatic Ifng -/- mice in the absence of RSV infection. Furthermore, neither WT nor Ifng -/- mice exhibit apparent eosinophil infiltration during RSV infection alone. Together, these findings indicate that, despite its critical role in limiting eosinophilic inflammation during asthma, IFN-γ is not essential for protection against RSV-induced exacerbation of asthmatic inflammation in adult mice.

Zoonotic and antimicrobial-resistant Escherichia coli (hereafter, E. coli ) is a global public health threat which can lead to detrimental effects on human health. Here, we aim to investigate the antimicrobial resistance and the presence of mcr-1 gene in E. coli isolated from chicken feces. Ninety-four E. coli isolates were obtained from samples collected from different locations in Bangladesh, and the isolates were identified using conventional microbiological tests. Phenotypic disk diffusion tests using 20 antimicrobial agents were performed according to CLSI-EUCAST guidelines, and minimum inhibitory concentrations (MICs) were determined for a subset of samples. E. coli isolates showed high resistance to colistin (88.30%), ciprofloxacin (77.66%), trimethoprim/sulfamethoxazole (76.60%), tigecycline (75.53%), and enrofloxacin (71.28%). Additionally, the pathotype eaeA gene was confirmed in ten randomly selected E. coli isolates using primer-specific polymerase chain reaction (PCR). The presence of mcr-1 gene was confirmed using PCR and sequencing analysis in six out of ten E. coli isolates. Furthermore, sequencing and phylogenetic analyses revealed a similarity between the catalytic domain of Neisseria meningitidis lipooligosaccharide phosphoethanolamine transferase A (LptA) and MCR proteins, indicating that the six tested isolates were colistin resistant. Finally, the findings of the present study showed that E. coli isolated from chicken harbored mcr-1 gene, and multidrug and colistin resistance. These findings accentuate the need to implement strict measures to limit the imprudent use of antibiotics, particularly colistin, in agriculture and poultry farms.

Current evidence indicates that more than half of all antimicrobials are used in the animal food-producing sector, which is considered a significant risk factor for the development, spread, and existence of antimicrobial resistance (AMR) pathogens in animals, humans, and the environment. Among other factors, clinical etiology and the level of knowledge, attitudes, and practices (KAP) of veterinarians are thought to be responsible for inappropriate prescriptions in the animal-source protein production sector in lower-resource settings like Bangladesh. We performed this cross-sectional study to assess factors associated with veterinarians' antimicrobial prescription behavior and their KAP on antimicrobial use (AMU) and AMR in Bangladesh. Exploratory and multivariate logistic models were used to describe an association between knowledge, attitudes, and practices of AMU and AMR and demographic characteristics of veterinarians. The results demonstrated that when selecting an antimicrobial, there was no to minimal influence of culture and susceptibility tests and patients' AMU history but moderate to high influence of the farmer's economic condition and drug instructions among the veterinarians. The results also demonstrated that more than half of the veterinarians had correct KAP regarding AMU and AMR, while the rest had moderate or lower levels of KAP. The factor score analysis revealed that age, level of education, years of experience, gender, and previous training on AMU and AMR were the key influencing factors in their level of KAP. Adjusted logistic regression analysis showed that respondents' age, current workplace, and previous training on AMU and AMR had a positive association with increased KAP. Considering the results, it is imperative to include AMR issues on vet curricula, and to provide post-education training, awareness campaigns, easy access to, and dissemination of AMR resources. Increasing the veterinary services to the outreach areas of the country and motivating veterinarians to follow the national AMR guidelines could be some other potential solutions to tackle the over-prescriptions of antimicrobials.

Dementia and frailty increase health adversities in older adults, which are topics of growing research interest. Frailty is considered to correspond to a biological syndrome associated with age. Frail patients may ultimately develop multiple dysfunctions across several systems, including stroke, transient ischemic attack, vascular dementia, Parkinson's disease, Alzheimer's disease, frontotemporal dementia, dementia with Lewy bodies, cortico-basal degeneration, multiple system atrophy, amyotrophic lateral sclerosis, and Creutzfeldt-Jakob disease. Patients with dementia and frailty often develop malnutrition and weight loss. Rigorous nutritional, pharmacological, and non-pharmacological interventions generally are required for these patients, which is a challenging issue for healthcare providers. A healthy diet and lifestyle instigated at an early age can reduce the risk of frailty and dementia. For optimal treatment, accurate diagnosis involving clinical evaluation, cognitive screening, essential laboratory evaluation, structural imaging, functional neuroimaging, and neuropsychological testing is necessary. Diagnosis procedures best apply the clinical diagnosis, identifying the cause(s) and the condition(s) appropriate for treatment. The patient's history, caregiver's interview, physical examination, cognitive evaluation, laboratory tests, and structural imaging should best be involved in the diagnostic process. Varying types of physical exercise can aid the treatment of these disorders. Nutrition maintenance is a particularly significant factor, such as exceptionally high-calorie dietary supplements and a Mediterranean diet to support weight gain. The core purpose of this article is to investigate trends in the management of dementia and frailty, focusing on improving diagnosis and treatment. Substantial evidence builds the consensus that a combination of balanced nutrition and good physical activity is an integral part of treatment. Notably, more evidence-based medicine knowledge is required., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The scientific community has been releasing whole genomic sequences of SARS-CoV-2 to facilitate the investigation of molecular features and evolutionary history. We retrieved 36 genomes of 18 prevalent countries of Asia, Europe and America for genomic diversity and mutational analysis. Besides, we studied mutations in the RBD regions of Spike (S) proteins to analyze the drug efficiency against these mutations. In this research, phylogenenetic analysis, evolutionary modeling, substitution pattern analysis, molecular docking, dynamics simulation, etc. were performed. The genomic sequences showed >99% similarity with the reference sequence of China.TN93 + G was predicted as a best nucleotide substitution model. It was revealed that effective transition from the co-existing SARS genome to the SARS-CoV-2 and a noticeable positive selection in the SARS-CoV-2 genomes occurred. Moreover, three mutations in RBD domain, Val/ Phe367, Val/ Leu 382 and Ala/ Val522, were discovered in the genomes from Netherland, Bangladesh and the USA, respectively. Molecular docking and dynamics study showed RBD with mutation Val/Leu382 had the lowest binding affinity with remdesivir. In conclusion, the SARS-CoV-2 genomes are similar, but multiple degrees of transitions and transversions occurred. The mutations cause a significant conformational change, which are needed to be investigated during drug and vaccine development., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Neospora caninum is a protozoan parasite, the etiologic agent of Neosporosis-a common cause of abortion in cattle worldwide. Herd level prevalence of Neosporosis could be as high as 90%. However, there is no approved treatment and vaccines available for Neosporosis. MicroRNA (miRNA) based prophylaxis and therapeutics could be options for Neosporosis in cattle and other animals. The current study aimed to investigate the genome of Neospora caninum to identify and characterize the conserved miRNAs through Expressed Sequence Tags (ESTs) dependent homology search. A total of 1,041 mature miRNAs of reference organisms were employed against 336 non-redundant ESTs available in the genome of Neospora caninum . The study predicted one putative miRNA "nca-miR-9388-5p" of 19 nucleotides with MFEI value -1.51 kcal/mol and (A + U) content% 72.94% corresponding with its pre-miRNA. A comprehensive search for specific gene targets was performed and discovered 16 potential genes associated with different protozoal physiological functions. Significantly, the gene "Protein phosphatase" was found responsible for the virulence of Neospora caninum . The other genes were accounted for gene expression, vesicular transport, cell signaling, cell proliferation, DNA repair mechanism, and different developmental stages of the protozoon. Therefore, this study finding will provide pivotal information to future aspirants upon Bovine Neosporosis. It will also serve as the baseline information for further studies of the bioinformatics approach to identify other protozoal miRNAs., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Since its emergence, Canine Parvovirus type 2 (CPV-2) has been considered as a deadly pathogen in dogs with high mortality in puppies for its clinical gastroenteritis and severe haemorrhagic diarrhoea. Although several studies on CPV-2 were conducted in Bangladesh, molecular investigation is poorly understood. The aim of the study was molecular detection and phylogenetic analysis of CPV in diarrhoeic pet dogs. During Jan-July 2019, anal swabs were collected from 96 unvaccinated pet dogs with suspected CPV infection from Sylhet region of Bangladesh. The CPV infection was initially screened through rapid Immunochromatographic (IC) strip test, and then CPV-2 (VP2 gene) were detected by conventional PCR assay. Then the nucleotide sequence of amplified VP2 gene was compared with other CPV strains from GeneBank. Of the total samples, 17.7% (17/96) found positive in IC strip test, and 15.62% (15/96) were found positive in PCR assay by using primer pair P2 that detect original CPV-2 type. The IC test showed 100% sensitivity and 97.5% specificity with PCR. In sequence analysis, our isolates showed the highest 90.40% homology with the isolates of China and the USA. Our strains had also an evolutionary relationship with the other strains of CPV from China and India. This study demonstrates the presence of CPV-2 in Bangladesh and futher sequence analysis of more VP2 gene will help in details insight of the molecular and genetic evolution of CPV in Bangladesh., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Md. Mahfujur Rahman reports was provided by Sylhet Agricultural University. Md. Mahfujur Rahman reports a relationship with Sylhet Agricultural University that includes: employment., (© 2021 The Author(s).)

Feline panleukopenia virus (FPV) is a highly contagious infectious pathogen of cats globally. However, there is no information on the molecular identification and characterization of FPV in Bangladesh. Here, 8.16% (8/98) and 18.37% (18/98) of diarrheic cats tested positive for FPV by an immunochromatography (IC) test and PCR, respectively. The IC test showed 44.44% sensitivity and 100% specificity in comparison with PCR. Our newly sequenced Bangladeshi FPV strain (MN826076) showed the highest (99.71%) sequence identity to strains from the United Arab Emirates (UAE). Strain MN826076 contained two characteristic amino acid variations in VP2 identifying it as an FPV strain: valine at position 103 and aspartic acid at position 323. Phylogenetically, the VP2 of strain MN826076 was found to be closely related to 19 FPV strains, sharing the same clade., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Here, drug repurposing and molecular docking were employed to screen approved MPP inhibitors and their derivatives to suggest a specific therapeutic agent for the treatment of COVID-19. The approved MPP inhibitors against HIV and HCV were prioritized, while RNA dependent RNA Polymerase (RdRp) inhibitor remdesivir including Favipiravir, alpha-ketoamide were studied as control groups. The target drug surface hotspot was also investigated through the molecular docking technique. Molecular dynamics was performed to determine the binding stability of docked complexes. Absorption, distribution, metabolism, and excretion analysis was conducted to understand the pharmacokinetics and drug-likeness of the screened MPP inhibitors. The results of the study revealed that Paritaprevir (-10.9 kcal/mol) and its analog (CID 131982844) (-16.3 kcal/mol) showed better binding affinity than the approved MPP inhibitors compared in this study, including remdesivir, Favipiravir, and alpha-ketoamide. A comparative study among the screened putative MPP inhibitors revealed that the amino acids T25, T26, H41, M49, L141, N142, G143, C145, H164, M165, E166, D187, R188, and Q189 are at potentially critical positions for being surface hotspots in the MPP of SARS-CoV-2. The top 5 predicted drugs (Paritaprevir, Glecaprevir, Nelfinavir, and Lopinavir) and the topmost analog showed conformational stability in the active site of the SARS-CoV-2 MP protein. The study also suggested that Paritaprevir and its analog (CID 131982844) might be effective against SARS-CoV-2. The current findings are limited to in silico analysis and lack in vivo efficacy testing; thus, we strongly recommend a quick assessment of Paritaprevir and its analog (CID 131982844) in a clinical trial., (Copyright © 2021. Published by Elsevier Masson SAS.)

AGL, a 15-kDa lectin from Amaranthus gangeticus seeds was isolated using ion-exchange and gel filtration chromatography. AGL contained 8.55% of neutral sugar and became specifically inhibited by N-acetyl-D-galactosamine. Hemagglutination activity of the lectin was maximum over the pH range of 4.0-6.0 and temperatures of 30-60 °C though it lost the activity when treated with urea and EDTA. With an LC 50 value of 250 μg/ml, AGL showed mild toxicity against Artemia nauplii. It inhibited the growth of pathogenic bacteria like Shigella boydii, Shigella dysenteriae and Staphylococcus aureus when treated for 8 and 16 h, respectively, but lost the antibacterial activity during a 24 h treatment. AGL could not inhibit the growth of Escherichia coli and mitogenic growth (7.0-9.0%) was observed instead. AGL inhibited 37.14%, 65.71% and 82.85% of biofilm formation of Escherichia coli at the concentrations of 250, 500 and 1000 μg/ml, respectively. Marked inhibition of the proliferation of Ehrlich ascites carcinoma cells was determined when treated with various doses of AGL. AGL inhibited 65.89% and 81.25% of the in vivo growth of EAC cells in mice at the doses of 2.0 and 4.0 mg/kg/day, respectively. Significant alteration of the expression of apoptosis related genes Fas, NF-kB and MAPK were observed., Competing Interests: Declaration of competing interest Authors declare no conflict of interests., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Antimicrobial resistance (AMR) has become an emerging health issue globally, posing a threat to zoonotic pathogens and foodborne diseases. In Bangladesh, the poultry sector supplies the majority of the demand for animal-source protein. The irrational and excessive use of antimicrobials (AMU) has been observed in the poultry sector. The development of AMR is associated with many factors, including the knowledge and attitudes of poultry farmers. Therefore, AMR reduction requires intervention from all the stockholders, including the farmers who are considered as end users of antimicrobials. This current research conducted a cross-sectional study to assess the knowledge, attitudes, and practices (KAP) of poultry farmers on AMU and AMR in Bangladesh. We determined the KAP of poultry farmers (broiler and layer farmers) of some selected districts of the country using a tested and paper-based questionnaire. The results demonstrated that most of the respondents have insufficient KAP regarding AMU and AMR. The respondents used a variety of antimicrobials primarily in the treatment of various diseases in poultry. One-third of the farmers did not seek antimicrobials from registered vets. Instead, they depended on others or themselves. The factor score analysis further revealed that the farmers' demographic and socioeconomic variables were significant factors influencing the KAP. An adjusted logistic regression analysis showed that older farmers with 9-12 years of farming experience and graduate-level education, engaging in medium-sized layer farming, were more likely to have correct KAP on AMU and AMR. Further, farmers from the Cox's Bazar region showed correct knowledge, whereas farmers of the Chattogram region showed a correct attitude towards AMU and AMR. A Spearman's rank-order correlation revealed a positive association between knowledge-attitudes and knowledge-practices. The findings of the current investigation provide baseline evidence about the KAP of poultry farmers from low-income resources and offer insights into designing interventions and policies for the use of AMU and AMR in Bangladesh.

Cryptosporidium parvum , a predominant causal agent of a fatal zoonotic protozoan diarrhoeal disease called cryptosporidiosis, bears a worldwide public health concern for childhood mortality and poses a key threat to the dairy and water industries. MicroRNAs (miRNAs), small but powerful posttranscriptional gene silencing RNA molecules, regulate a variety of molecular, biological, and cellular processes in animals and plants. As to the present date, there is a paucity of information regarding miRNAs of C. parvum ; hence, this study was used to identify miRNAs in the organism using a comprehensible expressed sequence tag-based homology search approach consisting of a series of computational screening process from the identification of putative miRNA candidates to the functional annotation of the important gene targets in C. parvum . The results revealed a conserved miRNA that targeted 487 genes in the model organism ( Drosophila melanogaste r) and 85 genes in C. parvum , of which 11 genes had direct involvements in several crucial virulence factors such as environmental oocyst protection, excystation, locomotion, adhesion, invasion, stress protection, intracellular growth, and survival. Besides, 20 genes showed their association with various major pathways dedicated for the ribosomal biosynthesis, DNA repair, transportation, protein production, gene expression, cell cycle, cell proliferation, development, immune response, differentiation, and nutrient metabolism of the organism in the host. Thus, this study provides a strong evidence of great impact of identified miRNA on the biology, virulence, and pathogenesis of C. parvum . Furthermore, the study suggests that the detected miRNA could be a potential epigenomic tool for controlling the protozoon through silencing those virulent and pathway-related target genes., Competing Interests: Declaration Of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

The m 6 A RNA methylation is the most prevalent internal modification in mammalian mRNAs which plays critical biological roles by regulating vital cellular processes. Dysregulations of the m 6 A modification due to aberrant expression of its regulatory proteins are frequently observed in many pathological conditions, particularly in cancer. Normal cells undergo malignant transformation via activation or modulation of different oncogenic signaling pathways through complex mechanisms. Accumulating evidence showing regulation of oncogenic signaling pathways at the epitranscriptomic level has added an extra layer of the complexity. In particular, recent studies demonstrated that, in many types of cancers various oncogenic signaling pathways are modulated by the m 6 A modification in the target mRNAs as well as noncoding RNA transcripts. m 6 A modifications in these RNA molecules control their fate and metabolism by regulating their stability, translation or subcellular localizations. In this review we discussed recent exciting studies on oncogenic signaling pathways that are modulated by the m 6 A RNA modification and/or their regulators in cancer and provided perspectives for further studies. The regulation of oncogenic signaling pathways by the m 6 A modification and its regulators also render them as potential druggable targets for the treatment of cancer.

The study was carried out to determine the prevalence and associated risk factors of theileriosis in goats of Chattogram district, Bangladesh. Molecular characterization of circulating Theileria in this area was also undertaken. A total of 400 samples were collected from goats of different breeds, ages and sex with relevant information of rearing and management. The prevalence of theileriosis was 8.50% (34/400) by polymerase chain reaction though all of those samples were test-negative by microscopic examination. Among different risk factors season, breed and tick infestation were found to be significantly (p ≤ 0.05) associated with the prevalence of theileriosis in goats. Serous nasal discharge and swollen lymph nodes were determined to be significant clinical signs. The Theileria spp. detected in the present study closely resemble isolates which were previously detected in Myanmar and China. Further large scale epidemiological studies are required to identify the circulating species and responsible vectors, which would facilitate control measures for this disease in Bangladesh., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Objective: Sleep apnea significantly decreases the quality of life. The apnea hypopnea index (AHI) is the main indicator for sleep apnea diagnosis. This study explored a novel automatic algorithm to diagnose sleep apnea from nasal airflow (AF) and pulse oximetry (SpO 2 ) signals., Approach: Of the 988 polysomnography (PSG) records from the sleep heart health study (SHHS), 45 were randomly selected for the development of an algorithm and the remainder for validation (n = 943). The algorithm detects apnea events by a digitization process, following the determination of the peak excursion (peak-to-trough amplitude) from AF envelope. Hypopnea events were determined from the AF envelope and oxygen desaturation with correction to time lag in SpO 2 . Total sleep time (TST) was estimated from an optimized percentage of artefact-free total recording time. AHI was estimated from the number of detected events divided by the estimated TST. The estimated AHI was compared to the scored SHHS data for performance evaluation., Main Results: The validation showed good agreement between the estimated and scored AHI (intraclass correlation coefficient of 0.95 and mean ±95% limits of agreement of -1.6 ±12.5 events h -1 ). The diagnostic accuracies were found: 90.7%, 91%, and 96.7% for AHI cut-off ≥5, ≥15, and ≥30 respectively., Significance: The new algorithm is accurate over other existing methods for the automatic diagnosis of sleep apnea. It is applicable to any portable sleep screeners especially for the home diagnosis of sleep apnea.

Colistin (polymyxin E) is widely used in animal and human medicine and is increasingly used as one of the last-resort antibiotics against Gram-negative bacilli. Due to the increased use of colistin in treating infections caused by multidrug-resistant Gram-negative bacteria, resistance to this antibiotic ought to be monitored. The study was undertaken to elucidate the molecular mechanisms, genetic relationships and phenotype correlations of colistin-resistant isolates. Here, we report the detection of the mcr-1 gene in chicken-associated Salmonella isolates in Bangladesh and its in-silico functional analysis. Out of 100 samples, 82 Salmonella spp. were isolated from chicken specimens (liver, intestine). Phenotypic disc diffusion and minimum inhibitory concentration (MIC) assay using different antimicrobial agents were performed. Salmonella isolates were characterized using PCR methods targeting genus-specific invA and mcr-1 genes with validation for the functional analysis. The majority of the tested Salmonella isolates were found resistant to colistin (92.68%), ciprofloxacin (73.17%), tigecycline (62.20%) and trimethoprim/sulfamethoxazole (60.98%). When screened using PCR, five out of ten Salmonella isolates were found to carry the mcr-1 gene. One isolate was confirmed for Salmonella enterica subsp. enterica serovar Enteritidis, and other four isolates were confirmed for Salmonella enterica subsp. enterica serovar Typhimurium. Sequencing and phylogenetic analysis revealed a divergent evolutionary relationship between the catalytic domain of Neisseria meningitidis lipooligosaccharide phosphoethanolamine transferase A (LptA) and MCR proteins, rendering them resistant to colistin. Three-dimensional homology structural analysis of MCR-1 proteins and molecular docking interactions suggested that MCR-1 and LptA share a similar substrate binding cavity, which could be validated for the functional analysis. The comprehensive molecular and in-silico analyses of the colistin resistance mcr-1 gene of Salmonella spp. of chicken origin in the present study highlight the importance of continued monitoring and surveillance for antimicrobial resistance among pathogens in food chain animals.

Anorectal malformations (ARM) incorporate a broad spectrum of diseases, can affect both sexes, and involve the distal anus and rectum as well as the uro-genital tracts. Defects range from the minor which can be treated easily with an excellent outcome, to those are complex and often associated with other anomalies are difficult to manage with poor functional prognosis. This study was done to observe the hospital incidence of Anorectal malformations, frequency of types, sex distribution and spectrum of associations with ARM. The effects of presence of associated anomalies on morbidity and mortality also observed. Detailed history, clinical examinations and relevant investigations were performed for the primary and as well as the associated anomalies. A total of 80 patients were admitted in the department of pediatric surgery in Mymensingh Medical College Hospital during the period of June 2016 to May 2017. Age of the patients was ranging from 1-180 days with the mean age of 0.49±1.002 months. Male: Female ratio was 1.6: 1. Among them 48(60%) were high and 32(40%) were low variety of ARM. In male 37(46.2%) had high and 13(13.7%) were low variety whereas in female 11(13.7%) were high and 19(23.7%) had low ARM. Associated anomalies were seen in 25(31.2%) patient -18 in males and 7 in females; 20 in high and 5 in low ARM. Associated anomalies were uro-genital 11(13.8%), cardiovascular 10(12.5%), vertebral 4(5%), limb defects 3(3.5%) and others 2(2.5%). Four patients have more than one anomaly. Anorectal malformations occur more in boys than girls. Males were more likely to have high lesions and without fistula was the common defect. Low variety ARM were found more in females with Anovestibular fistula is the commonest defect. The most common associated anomalies were recto urinary fistula (13.8%). Associations were more in high than low ARM but not significant (p>0.05). Post operative complications were more in high ARM in both sexes with associated anomalies. The effects of types and associations on morbidity and mortality were significantly different (p<0.05).

Problem: Artificial insemination, which requires cryopreservation of semen, is not completely optimized in goats because bucks discharge a small volume of ejaculate and seminal plasma (SP) contains specific proteins that are detrimental to spermatozoa at cryopreservation. However, it is not known the effects of sperm washing (removal of SP) before cryopreservation on the post-thawing frozen spermatozoa of Black Bengal bucks. Moreover, it is completely unknown whether SP of goats contains TGF-β and CXCL10 that have been proven essential for fertility in other mammals., Methods: Thirty-five ejaculates were collected from six mature Black Bengal bucks at one-week intervals and were subjected to microscopic evaluation for semen characteristics at pre- and post-freezing condition. The concentrations of TGF-β and CXCL10 in the SP using ELISA were determined. SP was harvested with centrifugation of fresh semen at 1500 g for 15 minutes twice at room temperature., Results: Semen characteristics were significantly varied between bucks. Seminal plasma of all ejaculates contained TGF-β and CXCL10 while significant variation of concentrations between bucks was observed in case of CXCL10. Cryopreservation of semen reduced total motility and progressive motility, while sperm washing before cryopreservation was beneficial to the total motility and progressive motility of post-thawing spermatozoa., Conclusion: Black Bengal buck seminal plasma was affluent of TGF-β and CXCL10 and washing of spermatozoa before cryopreservation was beneficial to the post-thawing sperm motility. The results of the current investigation will be helpful for future research on the roles of SP in female reproductive tract and pregnancy in Black Bengal goats., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

SARS-CoV-2, a new coronavirus strain responsible for COVID-19, has emerged in Wuhan City, China, and continuing its global pandemic nature. The availability of the complete gene sequences of the virus helps to know about the origin and molecular characteristics of this virus. In the present study, we performed bioinformatic analysis of the available gene sequence data of SARS-CoV-2 for the understanding of evolution and molecular characteristics and immunogenic resemblance of the circulating viruses. Phylogenetic analysis was performed for four types of representative viral proteins (spike, membrane, envelope and nucleoprotein) of SARS-CoV-2, HCoV-229E, HCoV-OC43, SARS-CoV, HCoV-NL63, HKU1, MERS-CoV, HKU4, HKU5 and BufCoV-HKU26. The findings demonstrated that SARS-CoV-2 exhibited convergent evolutionary relation with previously reported SARS-CoV. It was also depicted that SARS-CoV-2 proteins were highly similar and identical to SARS-CoV proteins, though proteins from other coronaviruses showed a lower level of resemblance. The cross-checked conservancy analysis of SARS-CoV-2 antigenic epitopes showed significant conservancy with antigenic epitopes derived from SARS-CoV. Descriptive epidemiological analysis on several epidemiological indices was performed on available epidemiological outbreak information from several open databases on COVID-19 (SARS-CoV-2). Satellite-derived imaging data have been employed to understand the role of temperature in the environmental persistence of the virus. Findings of the descriptive analysis were used to describe the global impact of newly emerged SARS-CoV-2, and the risk of an epidemic in Bangladesh., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Glucosylceramide synthase (GCS) is a key enzyme catalyzing ceramide glycosylation to generate glucosylceramide (GlcCer), which in turn serves as the precursor for cells to produce glycosphingolipids (GSLs). In cell membranes, GSLs serve as essential components of GSL-enriched microdomains (GEMs) and mediate membrane functions and cell behaviors. Previous studies showed that ceramide glycosylation correlates with upregulated expression of p53 hotspot mutant R273H and cancer drug resistance. Yet, the underlying mechanisms remain elusive. We report herewith that globotriaosylceramide (Gb3) is associated with cSrc kinase in GEMs and plays a crucial role in modulating expression of p53 R273H mutant and drug resistance. Colon cancer cell lines, either WiDr homozygous for missense-mutated TP53 (R273H +/+ ) or SW48/TP53-Dox bearing heterozygous TP53 mutant (R273H /+ ), display drug resistance with increased ceramide glycosylation. Inhibition of GCS with Genz-161 (GENZ 667161) resensitized cells to apoptosis in these p53 mutant-carrying cancer cells. Genz-161 effectively inhibited GCS activity, and substantially suppressed the elevated Gb3 levels seen in GEMs of p53-mutant cells exposed to doxorubicin. Complex formation between Gb3 and cSrc in GEMs to activate β-catenin was detected in both cultured cells and xenograft tumors. Suppression of ceramide glycosylation significantly decreased Gb3-cSrc in GEMs, β-catenin, and methyltransferase-like 3 for m 6 A RNA methylation, thus altering pre-mRNA splicing, resulting in upregulated expression of wild-type p53 protein, but not mutants, in cells carrying p53 R273H. Altogether, increased Gb3-cSrc complex in GEMs of membranes in response to anticancer drug induced cell stress promotes expression of p53 mutant proteins and accordant cancer drug resistance., Competing Interests: Y. Y. Liu is a member of Scientific Advisory Board for Sanofi‐Genzyme., (©2020 The Authors. FASEB BioAdvances published by The Federation of American Societies for Experimental Biology.)

Multidrug-resistant Vibrio parahaemolyticus has become a significant public health concern. The development of effective drugs and vaccines against Vibrio parahaemolyticus is the current research priority. Thus, we aimed to find out effective drug and vaccine targets using a comprehensive genome-based analysis. A total of 4822 proteins were screened from V. parahaemolyticus proteome. Among 16 novel cytoplasmic proteins, 'VIBPA Type II secretion system protein L' and 'VIBPA Putative fimbrial protein Z' were subjected to molecular docking with 350 human metabolites, which revealed that Eliglustat, Simvastatin and Hydroxocobalamin were the top drug molecules considering free binding energy. On the contrary, 'Sensor histidine protein kinase UhpB' and 'Flagellar hook-associated protein of 25 novel membrane proteins were subjected to T-cell and B-cell epitope prediction, antigenicity testing, transmembrane topology screening, allergenicity and toxicity assessment, population coverage analysis and molecular docking analysis to generate the most immunogenic epitopes. Three subunit vaccines were constructed by the combination of highly antigenic epitopes along with suitable adjuvant, PADRE sequence and linkers. The designed vaccine constructs (V1, V2, V3) were analyzed by their physiochemical properties and molecular docking with MHC molecules- results suggested that the V1 is superior. Besides, the binding affinity of human TLR-1/2 heterodimer and construct V1 could be biologically significant in the development of the vaccine repertoire. The vaccine-receptor complex exhibited deformability at a minimum level that also strengthened our prediction. The optimized codons of the designed construct was cloned into pET28a(+) vector of E. coli strain K12. However, the predicted drug molecules and vaccine constructs could be further studied using model animals to combat V. parahaemolyticus associated infections., Competing Interests: The authors have declared that no competing interests exist.

Sleep apnea is a common sleep disorder that can significantly decrease the quality of life. An accurate and early diagnosis of sleep apnea is required before getting proper treatment. A reliable automated detection of sleep apnea can overcome the problems of manual diagnosis (scoring) due to variability in recording and scoring criteria (for example across Europe) and to inter-scorer variability. This study explored a novel automated algorithm to detect apnea and hypopnea events from airflow and pulse oximetry signals, extracted from 30 polysomnography records of the Sleep Heart Health Study. Apneas and hypopneas were manually scored by a trained sleep physiologist according to the updated 2017 American Academy of Sleep Medicine respiratory scoring rules. From pre-processed airflow, the peak signal excursion was precisely determined from the peak-to-trough amplitude using a sliding window, with a per-sample digitized algorithm for detecting apnea and hypopnea. For apnea, the peak signal excursion drop was operationalized at ≥85% and for hypopnea at ≥35% of its pre-event baseline. Using backward shifting of oximetry, hypopneas were filtered with ≥3% oxygen desaturation from its baseline. The performance of the automated algorithm was evaluated by comparing the detection with manual scoring (a standard practice). The sensitivity and positive predictive value of detecting apneas and hypopneas were respectively 98.1% and 95.3%. This automated algorithm is applicable to any portable sleep monitoring device for the accurate detection of sleep apnea.

Implications of lead (Pb) exposure in dysregulated spermatogenesis in sexually active individuals during adulthood is well established; however, the effect of Pb exposure on spermatogenesis in the early stages of puberty is not clear yet. Moreover, the mechanism of Pb mediated dysregulation of spermatogenesis in adults is also poorly understood. Exposure to environmental toxicants during puberty may cause serious consequences in adulthood causing developmental retardations, especially in the reproductive system. Here we investigated the effects of lead exposure on spermatogenesis at the onset of puberty and the underlying mechanisms of these effects. Male ICR mice were exposed to low (50 mg/L) and high (200 mg/L) doses of Pb through the drinking water for 90 days. At the end of this period, the blood Pb level of the low-dose and high-dose exposure groups were found 6.14 ± 0.34 μg/dL and 11.92 ± 2.92 μg/dL respectively which were in agreement with the US CDC-recommended (5 μg/dL) and Chinese CDC-recommended (10 μg/dL) reference blood Pb level for the children. Although no visible toxicity was observed in either group, Pb exposure caused considerable histopathological changes in testis and epididymis; increased sperm DNA fragmentation indices as well as disrupted sperm heads and head-neck conjunctions. Moreover, both low and high-dose Pb exposures caused aberrant expressions of several important spermatogenesis-related genes in epididymis and testis. These results suggest that although the blood Pb levels are close to the recommended-reference values, low dose Pb exposure at the onset of puberty can disrupt spermatogenesis-related gene expression and cause abnormal mouse spermatogenesis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

More than a hundred chemical modifications in coding and non-coding RNAs have been identified so far. Many of the RNA modifications are dynamic and reversible, playing critical roles in gene regulation at the posttranscriptional level. The abundance and functions of RNA modifications are controlled mainly by the modification regulatory proteins: writers, erasers and readers. Modified RNA bases and their regulators form intricate networks which are associated with a vast array of diverse biological functions. RNA modifications are not only essential for maintaining the stability and structural integrity of the RNA molecules themselves, they are also associated with the functional outcomes and phenotypic attributes of cells. In addition to their normal biological roles, many of the RNA modifications also play important roles in various diseases particularly in cancer as evidenced that the modified RNA transcripts and their regulatory proteins are aberrantly expressed in many cancer types. This review will first summarize the most commonly reported RNA modifications and their regulations, followed by discussing recent studies on the roles of RNA modifications in cancer, cancer stemness as wells as functional RNA modification machinery as potential cancer therapeutic targets. It is concluded that, while advanced technologies have uncovered the contributions of many of RNA modifications in cancer, the underlying mechanisms are still poorly understood. Moreover, whether and how environmental pollutants, important cancer etiological factors, trigger abnormal RNA modifications and their roles in environmental carcinogenesis remain largely unknown. Further studies are needed to elucidate the mechanism of how RNA modifications promote cell malignant transformation and generation of cancer stem cells, which will lead to the development of new strategies for cancer prevention and treatment., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Ceramide (Cer) is an active cellular sphingolipid that can induce apoptosis or proliferation-arrest of cancer cells. Nanoparticle-based delivery offers an effective approach for overcoming bioavailability and biopharmaceutics issues attributable to the pronounced hydrophobicity of Cer. Missense mutations of the protein p53, which have been detected in approximately 42% of cancer cases, not only lose the tumor suppression activity of wild-type p53, but also gain oncogenic functions promoting tumor progression and drug resistance. Our previous works showed that cellular Cer can eradicate cancer cells that carry a p53 deletion-mutation by modulating alternative pre-mRNA splicing, restoring wild-type p53 protein expression. Here, we report that new ceramide-rubusoside (Cer-RUB) nanomicelles considerably enhance Cer in vivo bioavailability and restore p53-dependent tumor suppression in cancer cells carrying a p53 missense mutation. Natural RUB encapsulated short-chain C 6 -Cer so as to form Cer-RUB nanomicelles (∼32 nm in diameter) that substantially enhanced Cer solubility and its levels in tissues and tumors of mice dosed intraperitoneally. Intriguingly, Cer-RUB nanomicelle treatments restored p53-dependent tumor suppression and sensitivity to cisplatin in OVCAR-3 ovarian cancer cells and xenograft tumors carrying p53 R248Q mutation. Moreover, Cer-RUB nanomicelles showed no signs of significant nonspecific toxicity to noncancerous cells or normal tissues, including bone marrow. Furthermore, Cer-RUB nanomicelles restored p53 phosphorylated protein and downstream function to wild-type levels in p53 R172H /+ transgenic mice. Altogether, this study, for the first time, indicates that natural Cer-RUB nanomicelles offer a feasible approach for efficaciously and safely targeting cancers carrying p53 missense mutations., (©2019 American Association for Cancer Research.)

Sleep apnea elicits brain and physiological changes and its duration varies across the night. This study investigates the changes in the relative powers in electroencephalogram (EEG) frequency bands before and at apnea termination and as a function of apnea duration. The analysis was performed on 30 sleep records (375 apnea events) of older adults diagnosed with sleep apnea. Power spectral analysis centered on two 10-s EEG epochs, before apnea termination (BAT) and after apnea termination (AAT), for each apnea event. The relative power changes in EEG frequency bands were compared with changes in apnea duration, defined as Short (between 10 and 20 s), Moderate (between 20 and 30 s) and Long (between 30 and 40 s). A significant reduction in EEG relative powers for lower frequency bands of alpha and sigma were observed for the Long compared to the Moderate and Short apnea duration groups at BAT, and reduction in relative theta, alpha and sigma powers for the Long compared to the Moderate and Short groups at AAT. The proportion of apnea events showed a significantly decreased trend with increased apnea duration for non-rapid eye movement sleep but not rapid eye movement sleep. The proportion of central apnea events decreased with increased apnea duration, but not obstructive episodes. The findings suggest EEG arousal occurred both before and at apnea termination and these transient arousals were associated with a reduction in relative EEG powers of the low-frequency bands: theta, alpha and sigma. The clinical implication is that these transient EEG arousals, without awakenings, are protective of sleep. Further studies with large datasets and different age groups are recommended., (© 2019 European Sleep Research Society.)

Foot and mouth disease (FMD) is a highly contagious and devastating viral disease among all cloven-footed animals. In Bangladesh, the disease is endemic, with outbreaks occurring throughout the year in the haor regions. Thus, the FMD outbreaks impact livelihoods in the haor area and are of great concern. Therefore, a cross-sectional study was undertaken to evaluate the prevalence, distribution, and risk factors for clinical FMD in some selected areas of haor in Sylhet division of Bangladesh. We examined 1,388 cattle, of which 343 were clinically affected with FMD (prevalence 24.71%, CI95% = 22.44 - 26.98) during the period from July 2017 through June 2018. Though production loss was observed, no mortality was recorded in the infected animals. The data article shows the spatial distribution of FMD prevalence. The temporal pattern indicates a higher number of FMD cases in June (47.01%, CI95% = 38.97 - 55.07). The gender was found associated (OR = 2.98; p < 0.001) with the potential risk of FMD occurrence through univariate analysis. Besides, indigenous breeds of cattle (OR = 2.83; p < 0.001) are found to be more susceptible to FMD compared to exotic and crossbreeds. The risk factors identified in this article will serve as a baseline for the development of risk based FMD control program in future., (© 2019 The Author(s).)

Neonatal sepsis is one of the most common reasons for admission to neonatal units in developing countries. It is also a major cause of mortality in both developed and developing countries. The type and pattern of organisms that cause neonatal sepsis changes over time and vary from one hospital to another hospital, even in the same country. In addition the causative organisms have developed increased drug resistance for the last two decades. Maternal, neonatal and environmental risk factors have contributed for the development of sepsis. To study the risk factors, causative organism and bacterial sensitivity pattern in cases of neonatal sepsis. This cross-sectional study was conducted over a period of six months. The study included 100 patients admitted at the neonatal ward of Department of Pediatrics, Community Based Medical College Bangladesh, Mymensingh, Bangladesh. Blood samples for culture were taken aseptically before starting antibiotic therapy. Microorganisms were isolated and identified by standard microbiological processes and antimicrobial sensitivity patterns were performed against amikacin, gentamicin, ceftriaxone, ciprofloxacin and ceftazidime. The factors which carried a significant risk for development of neonatal sepsis were low birth weight, preterm neonates, meconium stained liquor and prolonged rupture of membrane (>18 hours). Gram negative organisms predominated (68.8%) with Escherichia coli (33.3%) being the commonest. The gram negative bacteria which were isolated sensitive to amikacin, gentamicin and ceftriaxone. The organisms also relatively more sensitive to ciprofloxacin and highly sensitive to ceftazidime. The Gram positive bacteria showed sensitivity against only the antibiotic Ceftriaxone and Ciprofloxacin. The overall mortality was 9%. The outcome of the study will contribute to preventing and treating neonatal sepsis in the hospital.

MytiLec-1, a 17 kDa lectin with β-trefoil folding that was isolated from the Mediterranean mussel ( Mytilus galloprovincialis ) bound to the disaccharide melibiose, Galα(1,6) Glc, and the trisaccharide globotriose, Galα(1,4) Galβ(1,4) Glc. Toxicity of the lectin was found to be low with an LC 50 value of 384.53 μg/mL, determined using the Artemia nauplii lethality assay. A fluorescence assay was carried out to evaluate the glycan-dependent binding of MytiLec-1 to Artemia nauplii. The lectin strongly agglutinated Ehrlich ascites carcinoma (EAC) cells cultured in vivo in Swiss albino mice. When injected intraperitoneally to the mice at doses of 1.0 mg/kg/day and 2.0 mg/kg/day for five consecutive days, MytiLec-1 inhibited 27.62% and 48.57% of cancer cell growth, respectively. Antiproliferative activity of the lectin against U937 and HeLa cells was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in vitro in RPMI-1640 medium. MytiLec-1 internalized into U937 cells and 50 μg/mL of the lectin inhibited their growth of to 62.70% whereas 53.59% cell growth inhibition was observed against EAC cells when incubated for 24 h. Cell morphological study and expression of apoptosis-related genes (p53, Bax, Bcl-X, and NF-κB) showed that the lectin possibly triggered apoptosis in these cells.