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Differentiation of naïve peripheral B cells into terminally differentiated plasma cells is characterized by epigenetic alterations, yet the epigenetic mechanisms that control B-cell fate remain unclear. Here, we identified a role for the histone H3K79 methyltransferase DOT1L in controlling B-cell differentiation. Mouse B cells lacking Dot1L failed to establish germinal centers (GC) and normal humoral immune responses in vivo. In vitro, activated B cells in which Dot1L was deleted showed aberrant differentiation and prematurely acquired plasma cell characteristics. Similar results were obtained when DOT1L was chemically inhibited in mature B cells in vitro. Mechanistically, combined epigenomics and transcriptomics analysis revealed that DOT1L promotes expression of a pro-proliferative, pro-GC program. In addition, DOT1L indirectly supports the repression of an anti-proliferative plasma cell differentiation program by maintaining the repression of Polycomb Repressor Complex 2 (PRC2) targets. Our findings show that DOT1L is a key modulator of the core transcriptional and epigenetic landscape in B cells, establishing an epigenetic barrier that warrants B-cell naivety and GC B-cell differentiation., (© 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)

MicroRNAs (miRNAs) play an important role in regulating gene expression, and myostatin (MSTN) has been widely recognized as a key gene for muscle growth and development. Through high-throughput sequencing to study the effects of starvation on miRNA transcriptomes in Larimichthys crocea muscle tissue, we found that the expression of miR-2014, miR-1231 and miR-1470 were significantly different between fasting and normal feeding Larimichthys crocea. Bioinformatics analysis predicted that miR-2014, miR-1231 and miR-1470 target MSTN mRNA 3'UTR. To verify the accuracy of predictions, we constructed double luciferase plasmids containing MSTN 3'UTR and confirmed that miR-2014-5p and miR-1231-5p can inhibit MSTN expression by targeting MSTN 3'UTR using double luciferase experiments, while miR-1470 is not involved in regulation. Subsequent site-directed mutation experiments reflected the specificity of the target sequence. In addition, quantitative PCR experiments revealed that miR-2014-5p and miR-1231-5p may participate in the regulation of MSTN expression in fasting and refeeding period, respectively. These results implied that miRNA may take part in muscle growth regulation during starvation. It provides some insights into the molecular regulation mechanism of MSTN in response to starvation stress in fish., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Medication adherence is challenging for older adults due to factors such as the number of medications, dosing schedule, and the duration of drug therapy. The objective of this study was to examine the effectiveness of an in-home electronic medication dispensing system (MDS) on improving medication adherence and health perception in older adults with chronic conditions., Methods: A pilot Randomized Controlled Trial (RCT) was conducted using a two-arm parallel assignment model. The intervention group used an MDS as their medication management method. The control group continued to use their current methods of medication management. Block randomization was used to assign participants into the intervention or control group. The inclusion criteria included 1) English speaking 2) age 50 and over 3) diagnosed with one or more chronic condition(s) 4) currently taking five or more oral medications 5) City of Calgary resident. Participants were recruited from a primary care clinic in Alberta, Canada. The study was open-label where knowledge about group assigned to participants after randomization was not withheld. Medication adherence was captured over a continuous, six-month period and analyzed using Intention-to-Treat (ITT) analysis., Results: A total of 91 participants were assessed for eligibility and 50 were randomized into the two groups. The number of participants analyzed for ITT was 23 and 25 in the intervention and control group, respectively. Most of the demographic characteristics were comparable in the two groups except the mean age of the intervention group, which was higher compared to the control group (63.96 ± 7.86 versus 59.52 ± 5.93, p-value = 0.03). The average recorded adherence over 26 weeks was significantly higher in the intervention group than the control group (98.35% ± 2.15% versus 91.17% ± 9.76%, p < 0.01). The self-rated medication adherence in the intervention group also showed a significant increase from baseline to 6-month (Z=-2.65, p < 0.01). The control group showed a non-significant increase (Z=-1.79, p = 0.07)., Conclusion: The MDS can be an effective, long-term solution to medication non-adherence in older adults experiencing chronic conditions and taking multiple medications. The technology induces better consistency and improvement in medication taking behaviour than simple, non-technological intervention., Trial Registration: Registered with ClinicalTrials.gov on April 09, 2020 with identifier NCT04339296 .

Nanosized extracellular vesicles (nEV) are released by all the eukaryotic cells into the extracellular spaces. They serve as crucial mediators of intercellular communication, and their presence has been detected in a variety of body fluids. nEV carry nucleic acids, lipids, proteins, and metabolites from the donor cells and transfer them to the recipient cells in the vicinity or distant locations to cause changes in their biological phenotypes. This very property of nEV makes them a suitable carrier of the drugs for therapeutic applications. The use of nEV as a drug delivery system offers several advantages over synthetic nanoparticles, including biocompatibility, natural targeting ability, and long-term safety. Further, nEV can be isolated from various biological sources, quickly loaded with the drug of choice, and modified to further enhance their utility as targeted drug delivery vehicles. Here we review these aspects of nEV and discuss the parameters that should be kept in mind while choosing the nEV source, drug loading method, and surface modification strategies. We also discuss the challenges associated with the nEV-based drug delivery platforms that must be overcome before realizing their full potential in clinical applications., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

An optical fiber having the properties of photonic crystal and offering new diversity and features beyond a conventional optical fiber is the photonic crystal fiber (PCF). In this paper, a simplified version of a highly sensitive plasmonic sensor, called a "slotted PCF based plasmonic biosensor," is studied numerically with asymmetric air holes using the finite element method. From numerical records through the interrogation method, the maximum obtained wavelength sensitivity and amplitude sensitivity are 22000 nm/RIU and 1782.56 R I U -1 , respectively, with a maximum wavelength resolution of 4.54×10 -6 R I U -1 RIU for the y -polarized mode. Finally, optimization of the sensor performance is scrutinized, and the effect of different parameters is studied with proper resonance wavelength curve fitting. The design structure of the fiber is simple, symmetrical, easy to fabricate, and cost effective and has higher sensitivity than other PCF based sensors. Having a symmetric orientation of air holes, classic geometric structure, and higher sensitivity, it has the capability to be used in sensing applications, refractive index detection, and identification of biochemicals, biomolecules, and other analytes.

The emission line intensities enhancement and sensitivity of laser-induced breakdown spectroscopy (LIBS) has been a subject of great interest for the last several years to improve the detection of the trace elements in soil and other environmental samples. Among several other methodologies, LIBS of the heated targets is emerging as one of the effective techniques to achieve the objective. We have investigated the effect of target heating (room temperature, 100°C, and 200°C) on the emission enhancement and plasma parameters of the laser-produced plasma on the soil sample containing 80 ppm lead. In addition, the limit of detection (LOD) of lead in soil has been determined at a fixed target temperature (200°C) and with varying lead concentration (20 ppm, 80 ppm, and 100 ppm) in the soil samples. With increasing the target temperature, not only do the emission line intensities, the excitation temperature, and electron number density increase, but also the spectral lines of Pb emerge, which were absent in the soil spectra recorded at room temperature. The limit of detection of lead in LIBS of the heated soil target has been determined as 3.8 ppm. This study reveals the potential application of the LIBS of a pre-heated target for the detection of lead with an improved LOD in the environmental sample.

The IL-33/ST2 axis is known to be involved in liver pathologies and IL-33 is over-expressed in mouse hepatitis models. We aimed to investigate the proposed protective effect of IL-33 in murine fulminant hepatitis induced by a Toll like receptor 3 (TLR3) viral mimetic, Poly I:C or by Concanavalin-A (ConA). The Balb/C mice were administered intravenously with ConA (15 mg/kg) or Poly I:C (30 μg/mouse) to induce acute hepatitis along with vehicle control. The recombinant mouse IL-33 (rIL-33) was injected (0.2 μg/mouse) to mice 2 h prior to ConA or Poly I:C injection to check its hepato-protective effects. The gross lesions, level of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), histopathology (H&E staining) and levels of IFNγ and TNFα were measured by ELISA. The gross pathological liver injury induced by Poly I:C or ConA was reduced by rIL-33 administration in mice. The levels of AST and ALT were significantly (P ≤ 0.05) higher in mice challenged with Poly I:C or ConA in comparison to control mice. The rIL-33 pre-treated mice in both Poly I:C and ConA challenge groups showed significantly (P ≤ 0.05) lower levels of AST and ALT, and decreased liver injury (parenchymal and per-vascular necrotic areas) in histological liver sections. The soluble levels of TNFα and IFNγ were significantly (P ≤ 0.05) raised in Poly I:C or ConA challenged mice than control mice. The levels of TNFα and IFNγ were significantly reduced (P ≤ 0.05) in rIL-33 pre-treated mice. In conclusion, the exogenous IL-33 administration mitigated liver injury and inflammation (decreased levels of IFNγ and TNFα) in Poly I:C and ConA-induced acute hepatitis in mice., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The main cause of hepatitis C is hepatitis C virus or HCV and for the cure of hepatitis C, NS3/4A protease has been found an important and emerging target. A number of HCV NS3/4A protease inhibitors have been discovered which have shown subsequent reduction in reducing the viral load leading to this infection however they are still undergoing clinical trials for improvement. Bacterial proteases are of great pharmaceutical importance and have a key role in various biological processes and in life cycle of several pathogens. The current study was planned to explore hexapeptides derived from conserved regions of bacterial proteases for their potential in blocking the NS3 protease activity of HCV which would finally inhibit HCV multiplication. For this, a novel protease gene nprB was isolated from a thermophilic bacterium Streptomyces thermovulgaris and bioinformatics analyses were performed. PCR amplification and sequencing of nprB gene indicated an open reading frame of 178 aa (20191.18 Dalton).The peptide GGVHIN was the top ranked with minimum S-score of -17.21) followed by hexapeptides VDAHAN, GVGREA, GALNES and VHINSS with their S-scores of -14.73, -13.78, -10.72 and -10.70, respectively. A phylogram was also reconstructed to reveal evolutionary relationships of nprB with its various homologs. The provided data will serve as a background to further reveal pharmaceutical and biotechnological importance of this novel protease gene from S. thermovulgaris in future.

Objective: To determine the role of heart fatty acid-binding protein in early detection of non-ST-elevation myocardial infarction and its comparison with two other cardiac markers., Methods: The cross-sectional study was conducted at Abbasi Shaheed Hospital, Karachi, from June 2012 to June 2014, and comprised patients presenting at the emergency department within two hours of chest pain and who were subsequently referred to the cardiology department with a provisional diagnosis of either unstable angina or non-ST-elevation myocardial infarction. Relevant history was taken on a specific proforma and electrocardiogram as well as routine investigations were done in the emergency department. Blood samples from the subjects were tested for the diagnosis of myocardial infarction through detection of heart fatty acid-binding protein, Troponin-I and Creatine kinase-myocardial band. Sensitivity and specificity of the three markers were calculated keeping coronary angiography as the gold standard. Data was analysed using SPSS 17., Results: Out of 250 patients, 153(61.2%) were males. The overall mean age was 54.45±13.92 years. Sensitivity and specificity of heart fatty acid-binding protein were 80.6% and 78.5% (p<0.05), for Troponin-I, 37.7% and 75% (p>0.05), and for Creatine Kinase-myocardial band, 29.5% and 67.8% (p>0.05)., Conclusions: Heart fatty acid-binding protein was found to be a good diagnostic tool for the detection of non-ST-elevation myocardial infarction.

Development of progenitor B cells (ProB cells) into precursor B cells (PreB cells) is dictated by immunoglobulin heavy chain checkpoint (IgHCC), where the IgHC encoded by a productively rearranged Igh allele assembles into a PreB cell receptor complex (PreBCR) to generate signals to initiate this transition and suppressing antigen receptor gene recombination, ensuring that only one productive Igh allele is expressed, a phenomenon known as Igh allelic exclusion. In contrast to a productively rearranged Igh allele, the Igh messenger RNA (mRNA) ( IgHR ) from a nonproductively rearranged Igh allele is degraded by nonsense-mediated decay (NMD). This fact prohibited firm conclusions regarding the contribution of stable IgHR to the molecular and developmental changes associated with the IgHCC. This point was addressed by generating the Igh Ter5H∆TM mouse model from Igh Ter5H mice having a premature termination codon at position +5 in leader exon of Igh Ter5H allele. This prohibited NMD, and the lack of a transmembrane region (∆TM) prevented the formation of any signaling-competent PreBCR complexes that may arise as a result of read-through translation across premature Ter5 stop codon. A highly sensitive sandwich Western blot revealed read-through translation of Igh Ter5H message, indicating that previous conclusions regarding a role of IgHR in establishing allelic exclusion requires further exploration. As determined by RNA sequencing (RNA-Seq), this low amount of IgHC sufficed to initiate PreB cell markers normally associated with PreBCR signaling. In contrast, the Igh Ter5H∆TM knock-in allele, which generated stable IgHR but no detectable IgHC, failed to induce PreB development. Our data indicate that the IgHCC is controlled at the level of IgHC and not IgHR expression., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

Thalassemia is a genetic haematological disorder that arises due to defects in the α and β-globin genes. Worldwide, 0.3-0.4 million children are born with haemoglobinopathies per year. Thalassemic patients, as well as their families, face various serious clinical, socio-economic, and psychosocial challenges throughout their life. Different therapies are available in clinical practice to minimize the suffering of thalassemic patients to some extent and potentially cure the disease. Predominantly, patients undergo transfusion therapy to maintain their haemoglobin levels. Due to multiple transfusions, the iron levels in their bodies are elevated. Iron overload results in damage to body organs, resulting in heart failure, liver function failure or endocrine failure, all of which are commonly observed. Certain drugs have been developed to enhance the expression of the γ-gene, which ultimately results in augmentation of fetal haemoglobin (HbF) levels and total haemoglobin levels in the body. However, its effectiveness is dependent on the genetic makeup of the individual patient. At present, allogeneic haematopoietic Stem Cell Transplantation (HSCT) is the only practically available option with a high curative rate. However, the outcome of HSCT is strongly influenced by factors such as age at transplantation, irregular iron chelation history before transplantation, histocompatibility, and source of stem cells. Gene therapy using the lentiglobin vector is the most recent method for cure without any mortality, graft rejection and clonal dominance issues. However, delayed platelet engraftment is being reported in some patients. Genome editing is a novel approach which may be used to treat patients with thalassemia; it makes use of targeted nucleases to correct the mutations in specific DNA sequences and modify the sequence to the normal wild-type sequence. To edit the genome at the required sites, CRISPR/Cas9 is an efficient and accurate tool that is used in various genetic engineering programs. Genome editing mediated by CRISPR/Cas9 has the ability to restore the normal β-globin function with minimal side effects. Using CRISPR/Cas9, expression of BCL11A can be downregulated along with increased production of HbF. However, these genome editing tools are still under in-vitro trials. CRISPR/Cas9 has can be used for precise transcriptional regulation, genome modification and epigenetic editing. Additional research is required in this regard, as CRISPR/Cas9 may potentially exhibit off-target activity and there are legal and ethical considerations regarding its use., (Copyright: © Amjad et al.)

Liver fibrosis (LF) is a progressive liver injury that may result in excessive accumulation of extracellular matrix (ECM). However, transforming growth factor-beta (TGF-β) and epithelial to mesenchymal transition (EMT) play a central role in the progression of LF through the activation of matrix producing hepatic stellate cells (HSCs). Piperlongumine (PL), an alkaloid extracted from Piper longum, has been reported to possess anti-inflammatory and antioxidant activities in various diseases but its hepatoprotective and antifibrotic effects have not been reported yet. Therefore, in the present study, we investigated the protective effect of PL in bile duct ligation (BDL)-induced LF model and explored the molecular mechanisms underlying its antifibrotic effect. BDL group displayed a significant degree of liver damage, oxidative-nitrosative stress, hepatic inflammation and collagen deposition in the liver while these pathological changes were effectively attenuated by treatment with PL. Furthermore, we found that PL treatment greatly inhibited HSCs activation and ECM deposition via downregulation of fibronectin, α-SMA, collagen1a, and collagen3a expression in the fibrotic livers. We further demonstrated that PL administration significantly inhibited TGF-β1/Smad and EMT signaling pathways. Our study demonstrated that PL exerted strong hepatoprotective and antifibrotic activities against BDL-induced LF and might be an effective therapeutic agent for the treatment of LF., 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.)

Coronavirus disease 2019 (COVID-19), apart from commonly involving the respiratory system, has its impact on the central nervous system, with a wide spectrum of clinical presentations ranging from headaches to ischemic strokes. The ongoing research regarding this novel disease has found that there is a very high prevalence of thrombotic episodes especially in critically ill patients when compared to severe presentation of other viral illnesses. This COVID-19-associated coagulopathy has a very complex etiology with the ability to form thrombus in arteries, veins, and microvasculatures of different organs. We present a unique case of a young woman with underlying COVID-19 who unfortunately developed locked-in syndrome due to bilateral pontine infarction during the course of her illness., (Copyright © 2020 Sattar, Iqbal, Haider, Zia, Niazi, Hanif, Ali and Khan.)

Following activation, conventional T (T conv ) cells undergo an mTOR-driven glycolytic switch. Regulatory T (T reg ) cells reportedly repress the mTOR pathway and avoid glycolysis. However, here we demonstrate that human thymus-derived T reg (tT reg ) cells can become glycolytic in response to tumour necrosis factor receptor 2 (TNFR2) costimulation. This costimulus increases proliferation and induces a glycolytic switch in CD3-activated tT reg cells, but not in T conv cells. Glycolysis in CD3-TNFR2-activated tT reg cells is driven by PI3-kinase-mTOR signalling and supports tT reg cell identity and suppressive function. In contrast to glycolytic T conv cells, glycolytic tT reg cells do not show net lactate secretion and shuttle glucose-derived carbon into the tricarboxylic acid cycle. Ex vivo characterization of blood-derived TNFR2 hi CD4 + CD25 hi CD127 lo effector T cells, which were FOXP3 + IKZF2 + , revealed an increase in glucose consumption and intracellular lactate levels, thus identifying them as glycolytic tT reg cells. Our study links TNFR2 costimulation in human tT reg cells to metabolic remodelling, providing an additional avenue for drug targeting.

Chronic kidney disease (CKD) is one of the greatest health burdens with an increasing global prevalence. Renal fibrosis (RF) is the hallmark of all forms of CKD which shows a strong positive correlation with severity of the disease. However, there are no therapeutic options available for treatment of RF. In the present study, we used an animal model based on unilateral ureteral obstruction (UUO), for renal injury and fibrosis. The UUO animals were treated with soluble guanylyl cyclase (sGC) stimulator, riociguat (RIO) (1, 3 and 10 mg/kg) to investigate its possible renoprotective effects. Kidneys of animals treated with RIO were found to show less abnormalities as compared to UUO control. Further, the levels of proinflammatory cytokines were reduced in RIO treated group. Furthermore, administration of RIO reduced expression of collagen-1, TGF-β, CTGF, α-SMA, vimentin along with transcription factors including Snail and Slug. The results of the present study provided strong evidence to support the antifibrotic activity of RIO., 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.)

Hollow-core fibers are advantageous for chemical sensing as they facilitate liquid infiltration into the core over conventional porous core fiber. In addition, the requirement of less bulk material significantly decreases the effective material loss (EML). In this paper, a six circular cladding tube negative curvature hollow-core fiber (NC-HCF) is proposed for chemical sensing. Five different chemicals including chloroform, polylactic acid, C C L 3 , glycerin, and benzene are proposed to fill the core of the NC-HCF, and sensitivities are evaluated by full vector finite element method-based COMSOL software. Numerical results reveal that the proposed sensor exhibits very high relative sensitivity in a wide range of frequency. The fabrication of the proposed fiber is feasible by existing fabrication facilities as it contains realistic fabrication parameters. Hence, the proposed sensor can potentially be used as a chemical sensor especially in the medical, food, and industrial sectors as the five chemicals mentioned above carry great medical and food significance.

Background: Apolipoprotein A-I (apoA-I) protects against atherosclerosis and participates in the removal of excess cellular cholesterol from peripheral organs. Several naturally occurring apoA-I mutations are associated with familial systemic amyloidosis, with deposition of amyloid aggregates in peripheral organs, resulting in multiple organ failure. Systematic studies on naturally occurring variants are needed to delineate their roles and involvement in pathogenesis., Methods: We performed a comparative structure-function analysis of five naturally occurring apoA-I variants and the wild-type protein. Circular dichroism, Fourier-transform infrared spectroscopy, thioflavin T and congo red fluorescence assays, thermal, chemical, and proteolytic stability assays, and 1,2-Dimyristoyl- sn -glycero-3-phosphocholine clearance analyses were used to assess the effects of mutations on the structure, function, stability, aggregation, and proteolytic susceptibility of the proteins to explore the mechanisms underlying amyloidosis and hypercholesterolemia., Results: We observed structural changes in the mutants independent of fibril formation, suggesting the influence of the surrounding environment. The mutants were involved in aggregate formation to varying degree; L170P, R173P, and V156E showed an increased propensity to aggregate under different physiological conditions. β sheet formation indicates that L170P and R173P participate in amyloid formation. Compared to WT, V156E and L170P exhibited higher capacity for lipid clearance., Conclusions: The selected point mutations, including those outside the hot spot regions of apoA-I structure, perturb the physiochemical and conformational behavior of the protein, influencing its function., General Significance: The study provides insights into the structure-function relationships of naturally occurring apoA-I variants outside the hot spot mutation sites., 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., (© 2020 The Authors.)

Takotsubo cardiomyopathy otherwise called stress cardiomyopathy, which results in debilitating of a segment of heart muscles, is a sort of non-ischemic cardiomyopathy, set off by stress. We describe two case reports of takotsubo cardiomyopathy triggered by the significant stressful event being the death of pet cats. The rare nature of the type of stressor and the manifestation is something to be considered by healthcare providers., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Hanif et al.)

Brucellosis is reportedly endemic in ruminants in Pakistan. Both Brucella abortus and B. melitensis infections have been decumented in domestic animals and humans in the country. This study aimed to identify the burden of anti- Brucella antibodies in small ruminants as well as associated potential risk factors with its occurrence at nine institutional livestock farms in Punjab, Pakistan. The sera collected from equal number of sheep and goats (500 from each species) were screened by indirect-ELISA for anti-smooth- Brucella antibodies followed by a serial detection by real-time PCR. Overall, 5.1% (51/1000) seropositivity was registered corresponding to 5% (25/500) prevalence in goats and 5.2% (26/500) in sheep. Brucella -DNA could not be detected in any of the tested sera by real-time PCR. Multiple logistic regression model indicated that farm location (OR 34.05), >4 years of age (OR 2.88), with history of reproductive disorders (OR 2.69), and with BCS of ≤ 3 (OR 12.37) were more likely to test positive for brucellosis at these farms. A routine screening, stringent biosecurity, and quarantine measures are warranted for monitoring and eradication of the infection. Similarly, isolation and molecular investigation of the etiologic agent(s) are needed to understand the relationship of epidemiology and out-breaks of brucellosis in the country., (Copyright © 2020 Ullah, Jamil, Melzer, Saqib, Hussain, Aslam, Jamil, Iqbal, Tahir, Ullah, Qureshi, Schwarz and Neubauer.)

Chicken type I interferons (type I IFNs) are key antiviral players of the chicken innate immune system and are considered potent antiviral agents against avian viral pathogens. Chicken type I IFNs are divided into three subtypes namely, chIFN-α, chIFN-β, and chIFN-κ. Viral pathogen-associated molecular patterns (PAMPs) recognized by their corresponding specific PRRs (pattern recognition receptors) induce the expression of chicken type I IFNs. Interaction of chicken type I IFNs with their subsequent IFN receptors results in the activation of the JAK-STAT pathway, which in turn activates hundreds of chicken interferon-stimulated genes (chISGs). These chISGs establish an antiviral state in neighboring cells and prevent the replication and dissemination of viruses within chicken cells. Chicken type I IFNs activate different pathways that constitute major antiviral innate defense mechanisms in chickens. However, evolutionary mechanisms in viruses have made them resistant to these antiviral players by manipulating host innate immune pathways. This review focuses on the underlying molecular mechanisms employed by avian RNA viruses to counteract chicken type I IFNs and chISGs through different viral proteins. This may help to understand host-pathogen interactions and the development of novel therapeutic strategies to control viral infections in poultry., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Bacterial proteases are of great pharmaceutical importance and have a key role in various biological processes and in life cycle of several pathogens. New technology used for rational protein engineering as well improved delivery options will expand the potential pharmaceutical applications of proteases. The catalytic proteases belong to metalloproteases (EC.3.4.24) that comprise thermo lysine. The metalloproteases and their homologs have many important biotechnological and therapeutic applications. In the present study, a novel protease gene nprB was isolated from a thermophilic bacterium Streptomyces thermovulgaris and bioinformatics analyses were performed. PCR amplification and sequencing of nprB gene indicated an open reading frame of 178 aa (20191.18 Dalton). Based on protein sequence homology as well as conserved motifs and PTF domain the protein is characterized as a thermo lysine-like protease and is a member of M4 family of metalloproteases. Different bioinformatics tools such as ProtParam, SOPMA, signalP4.1 and ProDom from the ExPAsy server were used for structural and functional analyses. A phylogram was also reconstructed to reveal evolutionary relationships of nprB with its various homologs. The provided data will serve as a background to further reveal pharmaceutical and biotechnological importance of this novel protease gene from S. thermovulgaris in future.

Honokiol is a phytochemical isolated from the Magnolia plant. It exhibits significant antitumor activity against a variety of cancer cell types via targeting of critical mediators of tumor progression, stromal remodeling, and chemoresistance. However, poor bioavailability and inefficient tumor uptake remain some of the hurdles in its translation as a therapeutically useful drug. Here, we developed a nanoformulation of honokiol using mesenchymal stem cell-derived exosomes, which are nonimmunogenic and express surface markers to support their tumor-targeted delivery. Maximum entrapment of honokiol occurred when it was mixed in a 1:4 weight ratio with exosomes and subjected to six cycles of sonication. Dynamic light scattering analysis demonstrated that the average size (∼175.3 nm), polydispersity (∼0.11), and integrity (∼12.9 mV) of exosomes remained in the desirable range post honokiol encapsulation. Exosome-encapsulated honokiol exhibited significantly higher therapeutic efficacy over the free honokiol in WST-1 growth and long-term clonogenicity assays. Flow cytometry-based cell cycle and live/dead cell assay, respectively, confirmed the enhanced effect of exosomal honokiol formulation on cell cycle arrest and apoptosis induction. More significant alterations in the expression of cell cycle- and survival-associated proteins were also observed in cancer cells treated with exosomal honokiol over free honokiol. Higher intracellular accumulation of honokiol was recorded in cancer cells treated with equivalent doses of honokiol as compared to the free honokiol. Together, our work is the first demonstration of exosomal encapsulation of honokiol and its improved antitumor efficacy resulting from improved cellular uptake., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Introduction: Intense livestock farming practices enforcing the farmers to use antibiotics as food supplements on a routine basis. Aberrant use of antibiotics is associated with the emergence of antibiotics resistance and resistant superbugs. Keeping in view the current scenario, the present study was designed for the first time from Pakistan with a specific aim to estimate the prevalence of the carbapenem-resistant Klebsiella pneumoniae in veterinary settings and the waste in Pakistan., Methods: A total of 138 samples from various veterinary sources were collected by employing a nonprobability sampling technique. Isolation and phenotypic identification of carbapenem-resistant K. pneumoniae were performed according to the CLSI standard. Molecular detection of various antibiotic resistance genes (ARGs) was done through PCR by using specific primers against each ARG. According to the pasture scheme, the multilocus sequence typing (MLST) was performed to characterize the K. pneumoniae sequence types (STs)., Results: According to the results of the study, overall 9.4% (13/138) isolates were confirmed carbapenem-resistant K. pneumoniae . Among various carbapenem ARGs particularly, the bla NDM-1 was found in 92.3% (12/13) isolates followed by bla OXA-48 84.6% (11/13). MLST results revealed that overall 3 STs were found in the study which includes ST29, ST11, and ST258. Taking together, this is the first study to our best knowledge which demonstrated the prevalence of carbapenem-resistant K. pneumoniae and its various STs prevalent in veterinary settings and the waste of Pakistan., Conclusion: Based on the above-mentioned facts, we suggested that veterinary settings and waste are the potential source and reservoir of carbapenem-resistant K. pneumoniae , which may be disseminated to the environment and ultimately can affect the public and companion livestock health., Competing Interests: The authors have no conflicts of interest to declare for this work., (© 2020 Chaudhry et al.)

Cytotoxic T cell differentiation is guided by epigenome adaptations, but how epigenetic mechanisms control lymphocyte development has not been well defined. Here we show that the histone methyltransferase DOT1L, which marks the nucleosome core on active genes, safeguards normal differentiation of CD8 + T cells. T cell-specific ablation of Dot1L resulted in loss of naïve CD8 + T cells and premature differentiation toward a memory-like state, independent of antigen exposure and in a cell-intrinsic manner. Mechanistically, DOT1L controlled CD8 + T cell differentiation by ensuring normal T cell receptor density and signaling. DOT1L also maintained epigenetic identity, in part by indirectly supporting the repression of developmentally regulated genes. Finally, deletion of Dot1L in T cells resulted in an impaired immune response. Through our study, DOT1L is emerging as a central player in physiology of CD8 + T cells, acting as a barrier to prevent premature differentiation and controlling epigenetic integrity., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

Due to the high electromagnetic interference (EMI) pollution, electromagnetic wave (EMW) absorption materials have risen as an important research area in material science and technology. Herein, the prepared carbonized ZIF-67 (CZIF) nanocomposites with polypyrrole (PPy) showed significantly enhanced electromagnetic wave absorption performance. The CZIF-PPy nanocomposites were prepared by the solvothermal and in-situ polymerization method. The CZIF-PPy nanocomposites possess a decent reflection loss (RL) value between the 2-18 GHz frequency range. The enhanced surface properties and magnetic-dielectric interfacial polarization plays an important role to achieve higher reflection loss and broader absorption bandwidth. This work explains the importance of magnetic-dielectric interface and may lead to design of more advanced hybrid electromagnetic wave absorption systems., 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.)

RAB proteins (RABs) represent the largest subfamily of Ras-like small GTPases that regulate a wide variety of endosomal membrane transport pathways. Their aberrant expression has been demonstrated in various malignancies and implicated in pathogenesis. Using The Cancer Genome Atlas (TCGA) database, we analyzed the differential expression and clinicopathological association of RAB genes in pancreatic ductal adenocarcinoma (PDAC). Of the 62 RAB genes analyzed, five (RAB3A, RAB26, RAB25, RAB21, and RAB22A ) exhibited statistically significant upregulation, while five ( RAB6B, RAB8B, RABL2A, RABL2B, and RAB32 ) were downregulated in PDAC as compared to the normal pancreas. Racially disparate expression was also reported for RAB3A, RAB25, and RAB26 . However, no clear trend of altered expression was observed with increasing stage and grade, age, and gender of the patients. PDAC from occasional drinkers had significantly higher expression of RAB21 compared to daily or weekly drinkers, whereas RAB25 expression was significantly higher in social drinkers, compared to occasional ones. The expression of RABL2A was significantly reduced in PDAC from diabetic patients, whereas RAB26 was significantly lower in pancreatitis patients. More importantly, a significant association of high expression of RAB21, RAB22A, and RAB25 , and low expression of RAB6B, RABL2A, and RABL2B was observed with poorer survival of PC patients. Together, our study suggests potential diagnostic and prognostic significance of RABs in PDAC, warranting further investigations to define their functional and mechanistic significance., Competing Interests: The authors declare no conflict of interest.

Background: Oxidative stress in adipocyte plays a central role in the pathogenesis of obesity as well as in the associated cardiovascular complications. The putative uremic toxin indoxyl sulfate induces oxidative stress and dramatically alters adipocyte phenotype in vitro . Mice that have undergone partial nephrectomy serve as an experimental model of uremic cardiomyopathy. This study examined the effects on adipocytes of administering a peptide that reduces oxidative stress to the mouse model., Methods: A lentivirus vector introduced the peptide NaKtide with an adiponectin promoter into the mouse model of experimental uremic cardiomyopathy, intraperitoneally. Then adipocyte-specific expression of the peptide was assessed for mice fed a standard diet compared with mice fed a western diet enriched in fat and fructose., Results: Partial nephrectomy induced cardiomyopathy and anemia in the mice, introducing oxidant stress and an altered molecular phenotype of adipocytes that increased production of systemic inflammatory cytokines instead of accumulating lipids, within 4 weeks. Consumption of a western diet significantly worsened the adipocyte oxidant stress, but expression of NaKtide in adipocytes completely prevented the worsening. The peptide-carrying lentivirus achieved comparable expression in skeletal muscle, but did not ameliorate the disease phenotype., Conclusions: Adipocyte-specific expression of NaKtide, introduced with a lentiviral vector, significantly ameliorated adipocyte dysfunction and uremic cardiomyopathy in partially nephrectomized mice. These data suggest that the redox state of adipocytes controls the development of uremic cardiomyopathy in mice subjected to partial nephrectomy. If confirmed in humans, the oxidative state of adipocytes may be a therapeutic target in chronic renal failure., (Copyright © 2020 by the American Society of Nephrology.)

Despite extensive vaccination approaches, Newcastle disease (ND) remains a permanent threat to the poultry industry worldwide. Besides vaccination, there is a burgeoning demand for new antivirals for use in interventions to control ND. One strategy is to strengthen the host innate immunity via host-derived innate immune proteins. Type I interferons define one of the first lines of innate immune defense against viral infections. Chicken interferon alpha (chIFN-α) is one of the potent cytokines that trigger antiviral responses. In the current study, we investigated the therapeutic effect of natural chIFN-α administered via oral and intramuscular (i.m.) routes against ND in broiler chickens. Our results showed that the level of protection against ND in response to chIFN-α therapy was dependent on the route and dose of IFN administration. A better therapeutic effect was observed in chickens treated with chIFN-α via the oral route than in those treated via the i.m. route. Regardless of the administration route, double-dose chIFN-α (2,000-U) treatments provided better protection than single-dose (1,000-U) treatments. However, complete protection against ND was achieved in birds treated with repeated doses of chIFN-α via the oral route. Histopathology of trachea, proventriculus, spleen, and liver showed a significant improvement in ND-induced degenerative changes in double-dose IFN-treatment groups compared to single-dose groups. Results of the hemagglutination test demonstrated a decrease in ND virus (NDV) titer in IFN-treated groups. Also, double doses of chIFN-α via oral route resulted in early recovery in weight gain. We propose that chIFN-α therapy via oral route could be an important therapeutic tool to control NDV infection in chicken. IMPORTANCE Newcastle disease (ND) is an economically important contagious disease of wild and domestic birds worldwide. The disease causes severe economic losses in terms of production due to high mortality and morbidity in nonvaccinated chickens. Despite extensive vaccination approaches, Newcastle disease (ND) remains a permanent threat to the poultry industry worldwide. In the current study, we used natural chicken IFN-α as an innate immune modulator to counteract ND in chickens. We report that chIFN-α is effective in protecting the chickens against ND and also prevents shedding of the virus, which can then prevent further spread of the disease. We propose that in addition to vaccination, chIFN-α therapy could be an effective option for controlling ND in areas of endemicity., (Copyright © 2020 Anjum et al.)

Viola tricolor Linn. is used as cardio-protective and anti-hypertensive agent in traditional medicine. Current study objective was to evaluate cardio-protective and hypotensive effects of Viola tricolor L. in vitro and in vivo studies. Viola tricolor L. crude extract (Vt.Cr) and its fractions (Aqueous and organic) were tested at rabbit atria and aorta coupled to Power Lab Data Acquisition System for cardio depressant and vasorelaxant effects in vitro whereas in vivo Blood Pressure was checked by invasive method in normotensive ketamine-diazepam anesthetized rats. Isoproterenol was employed for acute myocardial infarction (AMI) and left ventricular hypertrophy (LVH) development and cardioprotective effects of Vt.Cr were evaluated hemodynamically and histopathologically. Vt.Cr and its fractions decreased heart rate and contractile force in paired atria and relaxed Phenylephrine (1 µM) and K + (80 mM) stimulated contractions in aorta possibly mediated through Voltage dependent L-type calcium channels blockage supported by in vivo hypotensive action. In LVH, Vt.Cr lowered Angiotensin Converting Enzymes and renin, increased cyclic Guanosine Monophosphate and nitric oxide levels, decreased cardiomyocytes size and fibrosis attributed to Gallic acid as detected by High Performance Liquid Chromatography. Partial positive results were seen hemodynamically and histologically in AMI Viola tricolor L. showed vasorelaxant, cardio-relaxant, hypotensive, and cardio protective effect validating traditional practice in cardiovascular disorders., (© 2020 Federation of American Societies for Experimental Biology.)

Y-STR polymorphism of Gujjar population was determined by using AmpFISTR®YfilerTM PCR amplification kit. A total 176 haplotypes were obtained after the analysis of 17 Y-STR loci in 176 genetically unrelated individuals. Haplotype diversity and discrimination capacity attained was 0.99730 and 0.652201325, respectively. The comparison of Gujjar population with 16 other populations revealed that Gujjars have low genetic distance from Punjabi, Sindhi, and Pakhtun population of Pakistan; Azad Kashmir, Saraswat Brahmin from India; Bangladeshi population; north and south of Afghanistan; and Uttar Pradesh India which hints toward the migrational route Gujjars took over the centuries. This data is of significant value for population studies and forensic applications.

Y chromosomal short tandem repeat (Y-STR) haplotype diversity of 180 genetically unrelated male individuals from Sheikh population of Punjab Pakistan was studied by amplifying 17 Y-STR markers through the AmpFISTR®Yfiler™ PCR amplification kit. The analysis of data revealed mean discrimination capacity of 0.6438 and matching probability of 0.3561. Sheikh population was also compared with 11 other populations in order to determine its population relationships which indicated that Punjabi Sheikhs have low genetic resemblance with Indian-Balmiki, UAE [Arab], Yousafzai Pathan from Pakistan, and Pathans from Afghanistan. The data of this study could have valuable application in forensic cases, in population genetics studies, and in strengthening the Y-STR database.

Pancreatic cancer (PC) remains a therapeutic challenge because of its intrinsic and extrinsic chemoresistance mechanisms. Here, we report that C- X -C motif chemokine receptor 4 (CXCR4) and hedgehog pathways cooperate in PC chemoresistance via bidirectional tumor-stromal crosstalk. We show that when PC cells are co-cultured with pancreatic stellate cells (PSCs) they are significantly more resistant to gemcitabine toxicity than those grown in monoculture. We also demonstrate that this co-culture-induced chemoresistance is abrogated by inhibition of the CXCR4 and hedgehog pathways. Similarly, the co-culture-induced altered expression of genes in PC cells associated with gemcitabine metabolism, antioxidant defense, and cancer stemness is also reversed upon CXCR4 and hedgehog inhibition. We have confirmed the functional impact of these genetic alterations by measuring gemcitabine metabolites, reactive oxygen species production, and sphere formation in vehicle- or gemcitabine-treated monocultures and co-cultured PC cells. Treatment of orthotopic pancreatic tumor-bearing mice with gemcitabine alone or in combination with a CXCR4 antagonist (AMD3100) or hedgehog inhibitor (GDC-0449) displays reduced tumor growth. Notably, we show that the triple combination treatment is the most effective, resulting in nearly complete suppression of tumor growth. Immunohistochemical analysis of Ki67 and cleaved caspase-3 confirm these findings from in vivo imaging and tumor measurements. Our findings provide preclinical and mechanistic evidence that a combination of gemcitabine treatment with targeted inhibition of both the CXCR4 and hedgehog pathways improves outcomes in a PC mouse model., Competing Interests: Conflict of interest—The authors declare that they have no conflicts of interest with the contents of this article., (© 2020 Khan et al.)

Intensity-duration-frequency (IDF) curves can serve as useful tools in risk assessment of extreme environmental events. Thus, this study proposes an IDF approach for evaluating the risk of expected occurrences of extreme air pollution as measured by an air pollution index (API). Hourly data of Klang city in Malaysia from 1997 to 2016 are analyzed. For each year, a block maxima size is determined based on four different monsoon seasons. Generalized extreme value (GEV) distribution is used as a model to represent the probabilistic behavior of maximum intensity of the API, which is derived from each block. Based on the GEV model, the IDF curves are developed to estimate the extreme pollution intensities that correspond to various duration hours and return periods. Considering the IDF curves, we found that for any duration hour, the magnitude of pollution intensity tends to be high in parallel with increasing return periods. In fact, a high-intensity pollution event that poses a high risk of affecting the environment is less frequent than low-intensity pollution. In conclusion, the IDF curves provide a good basis for decision makers to assess the expected risk of extreme pollution events in the future., 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 Ltd. All rights reserved.)

Dengue fever is an arboviral infection spread by the Aedes mosquito with a wide spectrum of presentations encompassing simple flu-like illness to hemorrhagic manifestations. Hemorrhagic complications range from simple petechiae and purpura to gastrointestinal bleeding, hematuria, and severe central nervous system (CNS) bleeds. Herein we present a case of a 38-year-old male with dengue fever along with its hemorrhagic manifestations. Additionally, we conducted an extensive review of the literature to elucidate pathophysiology, diagnosis, and management of hemorrhagic manifestations in dengue fever., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Raza et al.)

Chronic kidney disease (CKD) has wide prevalence globally that affects a considerable population and has renal fibrosis (RF) as a hallmark feature. RF is characterized by abnormal deposition of extracellular matrix (ECM) in the interstitial space of renal tissue. There are only few studies where nanoparticles (NPs) were used for targeting the kidney mainly due to their size-dependent constraints. Further, most of the studies have been carried out in healthy animals. As the diseased kidney becomes susceptible to accumulation of nanoparticles, we hypothesized that nanoparticles (size ∼10 nm) could reach the kidney and might provide protective effects due to their inherent properties. We investigated the protective effects of cerium oxide nanoparticles (CONPs) with promising antioxidant activity in a CKD model. We, to the best of our knowledge, are first to report that CONPs abrogated RF by inhibiting transforming growth factor-β (TGF-β) signaling and epithelial-mesenchymal transition (EMT) in a fibrotic kidney.

In the continuous development of computer network technology, multimedia technology and information technology, digitization has become the main means of displaying information, thus facilitating the storage, copying and dissemination of digital multimedia information. In this context, there are no restrictions on arbitrary editing, copying, modification, and dissemination of digital images, music, etc., which leads to various social problems such as information security, copyright disputes, and piracy. With the advancement of networks and multimedia, digital watermarking technology has received worldwide attention as an effective method of copyright protection. Improving the anti-geometric attack ability of digital watermarking algorithms using image feature-based algorithms have received extensive attention. This paper proposes a novel robust watermarking algorithm based on SURF-DCT perceptual hashing (Speeded Up Robust Features and Discrete Cosine Transform), namely blind watermarking. The algorithm firstly uses the affine transformation with a feature matrix and chaotic encryption technology to preprocess the watermark image, enhance the confidentiality of the watermark, and perform block and DCT coefficients extraction on the carrier image, and then uses the positive and negative quantization rules to modify the DCT coefficients. The embedding of the watermark is completed, and the blind extraction of the watermark realized. Experiments show that the algorithm has good invisibility and strong robustness against conventional and geometric attacks and can effectively protect the security of images with NC value more than 90%., Competing Interests: The authors have no competing interests exists.

Herein, we report an eco-friendly, facile, one-pot, green synthesis of nanoceria for multiple biomedical applications. In the study, cerium oxide nanoparticles (CeO 2 -NPs) were synthesized using a simple aqueous extract of Aquilegia pubiflora as an effective reducing and capping agent. The biosynthesized nanoparticles were characterized via UV-vis spectroscopy, X-ray powder diffraction (XRD), high-performance liquid chromatography (HPLC), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Raman spectroscopy. The NPs were highly stable, exhibited high purity, and had a spherical morphology and mean size of 28 nm. FTIR and HPLC studies confirmed the successful capping of bioactive compounds on the nanoparticles. The well-characterized NPs were evaluated for a number of biomedical applications, and their antimicrobial (antifungal, antibacterial, and antileishmanial), protein kinase inhibition, anticancer, antioxidant, anti-diabetic and biocompatibility properties were studied. Our results showed that the Aquilegia pubiflora mediated CeO 2 -NPs were highly active against fungal strains, compared to the tested bacterial strains, with Aspergillus niger resulting in the largest zone of inhibition (15.1 ± 0.27 mm). The particles also exhibited dose dependent leishmanicidal activity with significant LC 50 values toward both the amastigote (114 μg mL -1 ) and promastigote (97 μg mL -1 ) forms of the parasite Leishmania tropica (KWH23). The NPs were found to be moderately active against the HepG2 cell line, showing 26.78% ± 1.16% inhibition at 200 μg mL -1 . Last but not least, their highly biocompatible nature was observed with respect to freshly isolated human red blood cells (hRBCs), making the greenly synthesized CeO 2 -NPs a novel candidates for multidimensional medical applications., Competing Interests: The authors declare no competing interests., (This journal is © The Royal Society of Chemistry.)

We have determined the absolute transition probabilities of 27 emission lines of neutral argon originating from the 3 p 5 4 p →3 p 5 4 s transition array in the wavelength region from 650 to 1100 nm using an argon-filled hollow cathode discharge lamp. The absolute transition probabilities have been deduced using the lifetimes of the upper levels and the measured branching fractions. Atomic oscillator strengths and relative line strengths for all the transitions have been computed using calculated transition probabilities. The experimentally determined transition probabilities are found to be in good agreement with that calculated in the intermediate coupling (IC) scheme. The comparison of experimentally determined transition probabilities with reported theoretical transition probabilities confirms that the IC scheme for the lower as well as for the upper levels seems to be a useful scheme for the level designation for the 3 p 5 4 p to 3 p 5 4 s configuration-based levels in argon. Furthermore, the measured relative line strengths are used to validate the J -file sum rule for the 3 p 5 4 p →3 p 5 4 s transition array of argon. The reported transition probabilities, oscillator strengths, and relative line strengths are compared with the published data, showing good agreement.

This study was conducted to reveal the prevalence, molecular characterization, and antibiotic susceptibility of Bacillus cereus isolated from dairy products including powdered infant formula, raw milk, pasteurized milk, ultra-high-temperature milk, and cheese. Five hundred samples collected from 5 provinces in China were analyzed in overall experiments. Multilocus sequence typing, distribution of toxin genes, and antibiotic susceptibility of the isolates were analyzed. Fifty-four B. cereus strains were detected; of these, 13 isolates (26%) were from raw milk, 12 isolates (12%) from pasteurized milk, 10 isolates (10%) from cheese, 12 isolates (8%) from ultra-high-temperature milk, and 7 isolates (7%) from powdered infant formula. These isolates were divided into 24 sequence types (ST); among them, ST24, ST26, ST82, ST142, ST377, ST857, and ST1046 were the main dominant ST. The results of detection of toxin genes (hblA, hblC, hblD, nheA, nheB, nheC, cytK, entFM, bceT, hlyII, and cesB) showed that 94.4% isolates carried nheABC genes, whereas only 11.1% of the isolates contained the hblACD gene cluster. In addition, detection rates of cytK, bceT, entFM, hlyII, and cesB genes were 75.9, 77.8, 85.2, 53.7, and 11.1%, respectively. The antibiotic susceptibility test indicated that most of B. cereus isolates were resistant to ampicillin, penicillin, cefepime, cephalothin, and oxacillin, and were susceptible to gentamicin, chloramphenicol, imipenem, tetracycline, ciprofloxacin, trimethoprim-sulfamethoxazole, erythromycin, kanamycin, and cefotetan. Therefore, this study revealed the prevalence and characteristics of B. cereus isolated from dairy products in China, indicating the potential risk and contributing to the effective prevention and control of this pathogen., (Copyright © 2020 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Background: Frail older patients are at risk of experiencing a decline in physical and cognitive function unrelated to the reason for admission. The Elder-Friendly Care (EFC) program was designed to improve the care, experiences, and outcomes of frail older adults. The project supported 8 Early Adoption Sites (EAS) in a large Canadian healthcare organization by providing multiple strategies, educational opportunities, and resources. The purpose of this study was to assess the usefulness of EFC educational materials and resources, staff practice changes and perceptions in pilot sites, and readiness for scale and spread., Methods: The study was conducted from May 2017 to June 2018 using a mixed-methods approach incorporating the Kirkpatrick Model of Training/Evaluation. A total of 76 Direct Care Staff participated in the staff survey, which assessed their awareness of, satisfaction with, and utilization of EFC principles, resources, and practices. Additionally, 12 interviews were conducted with staff who were directly involved in site implementation of EFC., Results: Most survey participants were aware (86%, n = 63) of the EFC program, and 85% (n = 41) indicated they or their site/unit had implemented EFC. Out of these 41 participants, the most common practice changes identified were: incorporating alternatives to restraint (81%, n = 33), decreased use of pharmacological restraint (78%, n = 32), and patient and family care planning (76%, n = 31). Participants that attended all 3 EFC Learning Workshops (LWs) were significantly more likely to recommend the EFC Toolkit to others (87% versus 40%; χ 2  = 8.82, p < 0.01) compared to participants attending less than 3 EFC LWs. Interview participants indicated that the program was well structured and flexible as sites/units could adopt changes that suited their individual sites, needs, contexts, and challenges., Conclusions: The educational materials and resources used for the EFC project are useful and appreciated by the Direct Care Staff. Further, participants perceive the EFC intervention as effective in creating positive practice change and useful in reducing hospital-related complications for older patients. Future implementation will investigate the impact of EFC on system-level outcomes in acute care.

Background: Present study was conducted to determine species composition of mosquitoes (larvae, pupae and adults) collected from ten different towns of Lahore from September 2014 to August 2015., Methods: Mosquito larvae, pupae and adults (male and female) were collected by using dippers and aspirators from September 2014 to August 2015 in different sites of Lahore comprising of ten towns i.e. Iqbal, Aziz Bhatti, Data Ganj Baksh, Gulberg, Nishtar, Ravi, Samanabad, Shalimar, Wagah, and Lahore Cantonment. Mosquito larvae and adults were identified by standard entomological keys. Diversity, richness and rarity of mosquito fauna were analyzed by the Shannon, Simpson and Margalef indices respectively., Results: In this study, a total of 8656 mosquitoes belonging to four genera namely Anopheles , Culex , Aedes and Mansonia were identified. Among fifteen species collected, Cx. quinquefasciatus was the most abundant species in the city having 25.8% relative abundance. However An. culicifacies s.l. ( sensu lato ) was reported as the least abundant species with 0.22% relative abundance. The highest diversity of mosquitoes was shown in the month of August (H= 2.25) while the lowest diversity was recorded June (H= 1.43). Extensive sewage water supported the maximum abundance of Cx. quinquifasciatus in urban areas of this city., Conclusions: This study has significantly elaborated the monthly varying species composition of mosquito fauna of this city. Hence this research will help us to find out the control strategies of mosquito borne diseases in this region., (Copyright© Iranian Society of Medical Entomology & Tehran University of Medical Sciences.)

Altered cellular metabolism is a hallmark of cancer. Metabolic rewiring in cancer cells occurs due to the activation of oncogenes, inactivation of tumor suppressor genes, and/or other adaptive changes in cell signaling pathways. Furthermore, altered metabolism is also reported in tumor-corrupted stromal cells as a result of their interaction with cancer cells or due to their adaptation in the dynamic tumor microenvironment. Metabolic alterations are associated with dysregulation of metabolic enzymes and tumor-stromal metabolic crosstalk is vital for the progressive malignant journey of the tumor cells. Therefore, several therapies targeting metabolic enzymes have been evaluated and/or are being investigated in preclinical and clinical studies. In this review, we discuss some important metabolic enzymes that are altered in tumor and/or stromal cells, and focus on their role in supporting tumor growth. Moreover, we also discuss studies carried out in various cancers to target these metabolic abnormalities for therapeutic exploitation., Competing Interests: Declaration of competing interest The authors declare that there are no conflict of interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The present study reports the convenient synthesis, spectroscopic characterization, bio-assays and computational evaluation of a novel series of N-acyl-1H-imidazole-1-carbothioamides. The screened derivatives displayed excellent antioxidant activity, moderate antibacterial and antifungal potential. The screened derivatives were found to be highly biocompatible against hRBCs. Molecular docking ascertained the mechanism and mode of action towards the molecular target delineating that ligands and complexes were stabilized at the active site by electrostatic and hydrophobic forces in accordance to the corresponding experimental results. Docking simulation provided additional information about the possibilities of inhibitory potential of the compounds against RNA. Computational evaluation predicted that N-acyl-1H-imidazole-1-carbothioamides 5c and 5g can serve as potential surrogates for hit to lead generation and design of novel antioxidant and antibacterial agents., (© 2020 Wiley-VHCA AG, Zurich, Switzerland.)

2D transition metal dichalcogenides (TMDs) have received widespread interest by virtue of their excellent electrical, optical, and electrochemical characteristics. Recent studies on TMDs have revealed their versatile utilization as electrocatalysts, supercapacitors, battery materials, and sensors, etc. In this study, MoS 2 nanosheets are successfully assembled on the porous VS 2 (P-VS 2 ) scaffold to form a MoS 2 /VS 2 heterostructure. Their gas-sensing features, such as sensitivity and selectivity, are investigated by using a quartz crystal microbalance (QCM) technique. The QCM results and density functional theory (DFT) calculations reveal the impressive affinity of the MoS 2 /VS 2 heterostructure sensor toward ammonia with a higher adsorption uptake than the pristine MoS 2 or P-VS 2 sensor. Furthermore, the adsorption kinetics of the MoS 2 /VS 2 heterostructure sensor toward ammonia follow the pseudo-first-order kinetics model. The excellent sensing features of the MoS 2 /VS 2 heterostructure render it attractive for high-performance ammonia sensors in diverse applications., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Lichens are composite organisms, comprising of a fungus (mycobiont) and a blue-green alga (photobiont). Along with the mycobiont, numerous non-obligate microfungi live in lichen thalli. These microfungi are called endolichenic fungi (ELF). In recent years, the ELF are emerging as promising natural sources because of their capability to exert unique drug molecules. The current study aimed to isolate the ELF from the lichen, Usnea longissima Ach., to control of biofilm formation and quorum sensing phenomenon in Pseudomonas aeruginosa PAO1, an opportunistic multidrug resistance pathogen that uses quorum sensing network to produce an array of pathogenic agents. Therefore, inhibiting quorum sensing to manage the infection caused by PAO1 could be the paramount alternative approach to conventional antibiotics. The isolated ELF was identified by amplifying the long subunit region of the fungal genome. The extracted metabolites of ELF (MELE) using the acetone solvent was further investigated for anti-quorum sensing activity using the biomarker strain Chromobacterium violaceum 12472 which exerts violacein pigment via the AHL mediated quorum sensing signalling. Moreover, the effect of MELE was also evaluated on the production of virulence factors and biofilm formation of P. aeruginosa PAO1. The molecular identification revealed that ELF (accession number MN171299) exhibited 100% similarity with Aspergillus quandricinctus strain CBS 135.52. The MELE showed significant anti-quorum sensing activity at the concentration of 4 mg/mL without affecting the bacterial cell viability of P. aeruginosa PAO1. The MELE diminished the production of virulence factors, including pyocyanin, protease, elastase, rhamnolipids, and extracellular polysaccharides of P. aeruginosa PAO1 in a concentration-dependent manner. The MELE also disturbed biofilm formation of P. aeruginosa PAO1. The 3-D analysis of biofilm architecture showed that the thickness and surface area covered by microcolonies was decreased as the concentration of MELE was increased. The GC-MS analysis of MELE exhibited that organic acids and fatty acids are major constituents of the MELE. The present study reports first time that the ELF, A. quandricinctus possesses potential to inhibit quorum sensing and biofilm formation of P. aeruginosa and can be further exploited for hospital and healthcare facilities., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest among them., (Copyright © 2019. Published by Elsevier Ltd.)

Renal fibrosis is a common pathological manifestation of almost all forms of kidney disease irrespective of the etiological cause. Microvascular rarefaction represents itself as an important phenomenon associated with renal fibrosis and shows strong correlation with decline in renal functions. Lysyl oxidase (LOX) catalyzes crosslinking of extracellular matrix (ECM) proteins including collagens, plays an important role in stabilization of degradation resistant matrix. Since, there seems to be a causal link between deposition of excessive ECM and microvascular rarefaction, we investigated the effects of reduction in renal fibrosis on microvascular rarefaction in acute as well as end stage kidney. We used a well-established unilateral ureteral obstruction (UUO)-induced renal fibrosis model to produce renal fibrosis in animals. We treated animals with a LOX inhibitor, β-aminopropionitrile (BAPN, 100 mg/kg, i.p.) and investigated effects on renal fibrosis and microvascular rarefaction. We observed that LOX inhibition was associated with reduction in collagen deposition in UUO-induced renal fibrosis animal model. Further, ECM normalization by LOX inhibition decreased the loss of peritubular capillaries (PTCs) in fibrotic kidney in acute study while the LOX inhibition failed to inhibit PTCs loss in end stage kidney. The results of present study suggested that inhibition of LOX reduces collagen deposition and renal fibrosis. Further, the reduction in fibrosis fails to protect from PTCs loss in chronic study suggesting the absence of strong link between reduction in fibrosis and improvement in PTCs in an end stage kidney., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Managing and taking multiple medications as prescribed can be a difficult task for older adults. In-home medication dispensing technologies could help enhance care. The objective of the study was to determine users' perspectives on a medication dispensing system (MDS) in supporting medication adherence of individuals living at home with chronic conditions., Methods: This analysis is a part of a randomized controlled trial on an MDS in a Western Canadian province. We interviewed participants who were recruited into the intervention group and started using an MDS. A maximum variation purposive sampling was used to select interview participants based on age, number of medications, and health conditions., Results: Thirteen participants were interviewed; most participants were females (n=11) and the average age was 63.7 (SD=8.2) years with an average of 8.9 (SD=3.6) prescribed medications. The most common health conditions were hypertension, diabetes, arthritis, and anxiety and depression. Four main themes emerged from thematic analysis: MDS acceptability, MDS patient support, need for the MDS, and areas of technology improvement. Most of the participants found the MDS to be acceptable and convenient, although privacy and security was an issue for some older adults. Audio and visual reminders and pre-organized medication supported participants' medication adherence and independence in daily routines. The perceived necessity of the MDS was split among participants with cost being one of the main concerns. Areas of technology improvement included the hard-to-open plastic medication packets and the sometimes inexact recording of medication adherence by the MDS if medications were dispensed on behalf of the patients., Conclusion: The MDS is an acceptable tool for improving medication management and adherence in older adults. Increased medication adherence may lead to patient and system-level benefits., Competing Interests: AA, VC, and MAA report grants from the Centre for Aging and Brain Health Innovation (CABHI), during the conduct of the study. The authors report no other conflicts of interest in this work., (© 2020 Ahmad et al.)

Earlier we have shown important roles of MYB in pancreatic tumor pathobiology. To better understand the role of MYB in the tumor microenvironment and identify MYB-associated secreted biomarker proteins, we conducted mass spectrometry analysis of the secretome from MYB-modulated and control pancreatic cancer cell lines. We also performed in silico analyses to determine MYB-associated biofunctions, gene networks, and altered biological pathways. Our data demonstrated significant modulation ( p < 0.05) of 337 secreted proteins in MYB-silenced MiaPaCa cells, whereas 282 proteins were differentially present in MYB-overexpressing BxPC3 cells, compared to their respective control cells. Alteration of several phenotypes such as cellular movement, cell death and survival, inflammatory response, protein synthesis, etc. was associated with MYB-induced differentially expressed proteins (DEPs) in secretomes. DEPs from MYB-silenced MiaPaCa PC cells were suggestive of the downregulation of genes primarily associated with glucose metabolism, PI3K/AKT signaling, and oxidative stress response, among others. DEPs from MYB-overexpressing BxPC3 cells suggested the enhanced release of proteins associated with glucose metabolism and cellular motility. We also observed that MYB positively regulated the expression of four proteins with potential biomarker properties, i.e., FLNB, ENO1, ITGB1, and INHBA. Mining of publicly available databases using Oncomine and UALCAN demonstrated that these genes are overexpressed in pancreatic tumors and associated with reduced patient survival. Altogether, these data provide novel avenues for future investigations on diverse biological functions of MYB, specifically in the tumor microenvironment, and could also be exploited for biomarker development.