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Background: Pathogenesis of acute kidney injury is driven by necro-inflammation, which is comprised of IL-1β mediated inflammation and RIP-1 mediated tubular necroptosis. HDAC6 is reported to regulate both inflammation and cell death. In the present study, we explored the role of HDAC6 in the lysosomal exocytosis of IL-1β and RIP-1 mediated necroptosis in the context of oxalate nephropathy., Methods: Raw 264.7 macrophages and NRK52E stimulated with oxalate crystals and LPS with or without HDAC6 inhibitor for in vitro experiments. Acute oxalate nephropathy was induced in C57BL/6 mice by injecting sodium oxalate (75 mg/kg). For the drug intervention study, Tubastain A (TSA) was given an hour before injection of sodium oxalate. Mice were sacrificed 24 hrs after the oxalate injection, blood and kidney were harvested. Blood samples were analyzed for BUN and IL-1β levels. Renal tissues were analyzed for histology, immunohistochemistry, RNA, and protein expression., Results: HDAC6 and IL-1β upregulated in crystal stimulated macrophages and acute oxalate nephropathy. Pre-treatment of macrophages with TSA reduced IL-1β in supernatant without affecting the expression of pro-IL-1β and mature IL-1β in cell lysate. The effect of TSA on IL-1β secretion was influenced by tubulin acetylation. Renal epithelial cell NRK52E stimulated with crystals showed upregulation of necroptosis pathway markers and concentration-dependent cell death. TSA inhibited RIP-1, RIP3, and MLKL expression along with p-MLKL in stimulated epithelial cells. TSA treatment of oxalate nephropathy mice showed decreased inflammation and tubular cell death by regulating IL-1β and necroptosis and reduced renal injury., Conclusion: This study highlights the role of HDAC6 in regulating the tubulin-mediated secretion of IL-1β and RIP kinase mediated necroptosis in acute oxalate nephropathy., (Copyright © 2022. Published by Elsevier B.V.)

A promising hydrazide based small molecule lead as a potent and selective histone deacetylase 3 (HDAC3) inhibitor has been developed from a small series of synthesized novel chemical entities. The lead compound (4e) displayed high HDAC3 inhibitory potency (IC 50  = 15.41 nM) and a minimum of 18-fold selectivity over other HDAC isoforms. It also exhibited potent cytotoxicity against several cancer cell lines with minimal toxicity against normal cell lines tested. Compound 4e also enhanced acetylation levels on H3K9, H4K12 and H3K27 both in vitro and in vivo. It also induced cell cycle arrest at the G2/M phase in B16F10 and 4T1 cells. It caused significant apoptosis and upregulated the expression of caspase-3, caspase-7, cytochrome c and downregulated the expression of BCL2 in tumour tissue. In addition, the downregulation of CD44, EGFR and Ki-67 suggested the potential of compound 4e in reducing cell proliferation and metastasis in mice. Further, a marked decrease in the tumour volume was observed with no general toxicity in the major organs when treated with 4e in the 4T1-Luc xenograft mouse model. Therefore, compound 4e is a promising candidate selectively targeting HDAC3 with a significant antitumour activity that can be evaluated further in preclinical and clinical evaluation., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: To achieve better academic performance, students should improve their cognitive faculties and overcome anxiety. Therefore, the present research was conducted to assess the effect of yoga on the cognitive functions of female adolescents with low academic performance., Methods: The present study is a randomized control trial (RCT). Eighty-nine female students in the age range of 12-14 years were randomly assigned into two groups [yoga (n = 45); physical exercise (n = 44)] at a school setting. Both groups were assessed before and after on Raven's standard progressive matrices (RSPM), Corsi Block Tapping Test (CBTT), Six Letter Cancellation Test (SLCT), Digit Letter Substitution Test (DLST), Stroop Color and Word Test (SCWT), and State-Trait Anxiety Inventory for Children (STAIC)., Results: Findings of the present study showed significant (p < .05) differences in scores of forward CBTT, SWCT, and SLCT in group × time interaction. Both the groups showed significant (p < .05) improvement in SLCT, backward scores of CBTT, and STAIC-T. All outcomes measured were significantly (p < .05) improved in the yoga group except STAIC-S., Conclusion: Yoga improves general intelligence, visuospatial working memory, and attention, as well as reduces the anxiety of students with low academic performance. Similarly, physical exercise was also found to be improving visuospatial working memory, sustained attention, and reduce trait anxiety. However, the finding of the present study indicated yoga to be more effective compared to physical exercise in regards to students' fluid intelligence and executive function. Improvement in general intelligence, visuospatial working memory, and attention is expected to positively influence students' academic performance., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Comparative genomic and functional analyses revealed the presence of three genomic islands (GIs, >50 Kb size): ICE nah CSV86, Pseudomonas bharatica genomic island-1 (PBGI-1), and PBGI-2 in the preferentially aromatic-degrading soil bacterium, Pseudomonas bharatica CSV86 T . Site-specific genomic integration at or near specific transfer RNAs (tRNAs), near-syntenic structural modules, and phylogenetic relatedness indicated their evolutionary lineage to the type-4 secretion system (T4SS) ICE clc family, thus predicting these elements to be integrative conjugative elements (ICEs). These GIs were found to be present as a single copy in the genome and the encoded phenotypic traits were found to be stable, even in the absence of selection pressure. ICE nah CSV86 harbors naphthalene catabolic ( nah - sal ) cluster, while PBGI-1 harbors Co-Zn-Cd ( czc ) efflux genes as cargo modules, whereas PBGI-2 was attributed to as a mixed-function element. The ICE nah CSV86 has been reported to be conjugatively transferred (frequency of 7 × 10 -8 /donor cell) to Stenotrophomonas maltophilia CSV89. Genome-wide comparative analyses of aromatic-degrading bacteria revealed nah - sal clusters from several Pseudomonas spp. as part of probable ICEs, syntenic to conjugatively transferable ICE nah CSV86 of strain CSV86 T , suggesting it to be a prototypical element for naphthalene degradation. It was observed that the plasmids harboring nah - sal clusters were phylogenetically incongruent with predicted ICEs, suggesting genetic divergence of naphthalene metabolic clusters in the Pseudomonas population. Gene synteny, divergence estimates, and codon-based Z -test indicated that ICE nah CSV86 is probably derived from PBGI-2, while multiple recombination events masked the ancestral lineage of PBGI-1. Diversifying selection pressure (dN-dS = 2.27-4.31) imposed by aromatics and heavy metals implied the modular exchange-fusion of various cargo clusters through events like recombination, rearrangement, domain reshuffling, and active site optimization, thus allowing the strain to evolve, adapt, and maximize the metabolic efficiency in a contaminated niche. The promoters (P nah and P sal ) of naphthalene cargo modules ( nah , sal ) on ICE nah CSV86 were proved to be efficient for heterologous protein expression in Escherichia coli . GI-based genomic plasticity expands the metabolic spectrum and versatility of CSV86 T , rendering efficient adaptation to the contaminated niche. Such isolate(s) are of utmost importance for their application in bioremediation and are the probable ideal host(s) for metabolic engineering., 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 Mohapatra, Malhotra and Phale.)

Introduction: Yoga as a holistic mind-body intervention is increasingly evaluated for the management of various autism symptoms in children with autism spectrum disorder (ASD)., Methodology: Forty-three children with ASD from 4 special schools were randomized into two groups, yoga group: 23 children and control group: 20 children. The yoga group received 12 weeks of yoga intervention in special schools., Results: Significant improvement in the yoga group was noted in the overall autism severity ( P < 0.001) as reported by the parents in comparison to the control group., Conclusion: The findings of the study show that yoga can have a positive impact on the symptomatology of autism., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Industrial Psychiatry Journal.)

Evidence supports a strong bidirectional association between depression and Type 2 diabetes mellitus (T2DM). The harmful impact of oxidative stress and chronic inflammation on the development of both disorders is widely accepted. Nuclear factor erythroid 2-related factor 2 (NRF2) is a pertinent target in disease management owing to its reputation as the master regulator of antioxidant responses. NRF2 influences the expression of various cytoprotective phase 2 antioxidant genes, which is hampered in both depression and T2DM. Through interaction and crosstalk with several signaling pathways, NRF2 endeavors to contain the widespread oxidative damage and persistent inflammation involved in the pathophysiology of depression and T2DM. NRF2 promotes the neuroprotective and insulin-sensitizing properties of its upstream and downstream targets, thereby interrupting and preventing disease advancement. Standard antidepressant and antidiabetic drugs may be powerful against these disorders, but unfortunately, they come bearing distressing side effects. Therefore, exploiting the therapeutic potential of NRF2 activators presents an exciting opportunity to manage such bidirectional and comorbid conditions., (Copyright © 2022 Elsevier B.V. All rights reserved.)

A space-dependent mortality assay was performed on thirty-one short-horned adult grasshopper species (Acridoidea: Orthoptera) to estimate the space required for mass culture of acridids in captivity. Our findings show that acridids have a multidimensional mortality mode at different densities. The correlations between density and mortality of acridids in rearing units follow a sigmoidal curve. Acridid mortality significantly increases with individual numbers up to a threshold, after which mortality does not change even if the density increases further. A log-logistic sigmoidal function expresses the dose (density)-response (mortality) relationship in the majority of acridid species. Mortality of acridids at variable densities does not necessarily correspond with the body-mass of the insects, indicating that mortality is a body-mass independent event. As a ready reference, a utility chart has been prepared, providing the necessary conversion factor for estimating space for a given number of acridids. The present information will be helpful for commercial grasshopper farming in captivity., Competing Interests: The authors have declared that no competing interests exist.

Total synthesis of the pentasaccharide related to the saponin isolated from the medicinal plant Aster tataricus L. f. is reported in the form of its allyl glycoside. The synthesis is accomplished by following a [3 + 2] block synthesis strategy where the trisaccharide acceptor and the disaccharide donor are rationally designed and obtained from semi-protected monosaccharides through stereoselective glycosylations either by activation of the thioglycoside or glycosyl trichloroacetimidate. The apiose moiety has been synthesized by literature procedure with little modification. The target pentasaccharide in the form of its allyl glycoside will be beneficial for further biological evaluation of the said structure and possible glycoconjugate formation as per need., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Pseudomonas sp. CSV86, an Indian soil isolate, degrades wide range of aromatic compounds like naphthalene, benzoate and phenylpropanoids, amongst others. Isolate displays the unique and novel property of preferential utilization of aromatics over glucose and co-metabolizes them with organic acids. Interestingly, as compared to other Pseudomonads, strain CSV86 harbours only high-affinity glucokinase pathway (and absence of low-affinity oxidative route) for glucose metabolism. Such lack of gluconate loop might be responsible for the novel phenotype of preferential utilization of aromatics. The genome analysis and comparative functional mining indicated a large genome (6.79 Mb) with significant enrichment of regulators, transporters as well as presence of various secondary metabolite production clusters, suggesting its eco-physiological and metabolic versatility. Strain harbours various integrative conjugative elements (ICEs) and genomic islands, probably acquired through horizontal gene transfer events, leading to genome mosaicity and plasticity. Naphthalene degradation genes are arranged as regulonic clusters and found to be part of ICE CSV86nah . Various eco-physiological properties and absence of major pathogenicity and virulence factors (risk group-1) in CSV86 suggest it to be an ideal candidate for bioremediation. Further, strain can serve as an ideal chassis for metabolic engineering to degrade various xenobiotics preferentially over simple carbon sources for efficient remediation., (© 2021 Society for Applied Microbiology and John Wiley & Sons Ltd.)

Assistive eco-physiological traits are necessary for microbes to adapt and colonize at polluted niches, enabling efficient clean-up. To demarcate species distinctiveness and eco-physiological traits of aromatic compounds metabolizing Pseudomonas sp. CSV86 T (earlier identified as Pseudomonas putida), an Indian isolate from a petrol station soil, comparative genome mining, taxono-genomic, and physiological analyses were performed. A 6.79 Mbp genome (62.72 G + C mol%) of CSV86 T encodes 6798 CDS and 238 unique genes. Naphthalene metabolism and Co-Zn-Cd resistance gene clusters were part of distinct genomic islands. Abundance of transporters (aromatics, organic acids, amino acids, and metals) and mobile elements (integrases, transposases, conjugative proteins) differentiated CSV86 T from its closest relatives. Enhanced siderophore production for Fe-uptake during aromatic metabolism, indole acetic acid production, and fusaric acid resistance wasvalidated by genomic attributes. Full-length 16S-rRNA phylogeny revealed Pseudomonas japonica WL T as a closest relative of CSV86 T . However, lower genomic indices (<97% gyrB-rpoB-rpoD homology, <90% ANI, <50% DNA-DNA relatedness) and taxonomic differences (assimilation of organic acids, amino acids, fatty acids composition) substantially differentiated CSV86 T from its closest relatives, indicating it to be a novel species as Pseudomonas bharatica. Preferential metabolism of aromatics with advantageous eco-physiological traits renders CSV86 T an ideal candidate for bioremediation and host for metabolic engineering., (© 2022 Society for Applied Microbiology and John Wiley & Sons Ltd.)

( E )-2-Trialkylsilyloxy-1,3-dienes and the corresponding 2-acetoxy derivatives participate in cobalt-catalyzed heterodimerization reactions with ethylene, giving mostly 4,1-hydrovinylation products with addition of the vinyl group to C 4 and H at C 1 of the diene. The reaction, which gives highly functionalized, protected enolates, is best carried out at room temperature with the diene dissolved in methylene chloride and ethylene delivered from a balloon in the presence of a catalyst generated in situ by the reaction of (P~P)CoCl 2 with methylaluminoxane (MAO). Commercially available chiral ligands, 2,3- O -isopropylidene-2,3-dihydroxy-1,4- bis -(diphenylphosphino)butane (DIOP) and 2,4- bis -diphenylphosphinopentane (BDPP) in combination with the earth-abundant metal cobalt, gave excellent regio- and enantio-selectivities (up to 99% ee) for the chiral enolate surrogates from both silyloxy and acetoxydienes. Hydrolyses of the silyl enol ethers lead to β-vinyl ketones, thus providing a practical two-step approach to these valuable synthons starting from α,β-unsaturated ketones and ethylene. The hydrovinylated silyl enol ethers undergo typical nucleophilic reactions such as alkylation, aldol, Michael and Mannich reactions with varying degrees of diastereoselectivity (2:1-13:1). The silyl enol ethers are convenient source of lithium enolates which are readily converted into other vinyl derivatives such as vinyl acetates and vinyl triflates. The vinyl triflates are excellent partners for cross-coupling chemistry, giving potentially useful, polyolefinic chiral synthons for further applications. Chemoselective reduction and hydrosilylation of the vinyl group in the chiral β-vinyl silyl enol ether further illustrate other potential reactivities of these versatile synthons. Since isolated cationic [(P~P)Co(I)] + [BARF] - appears to be an excellent catalyst for the heterodimerization of silyl enol ethers and ethylene giving products very similar in yield and selectivities to what is observed in the MAO-mediated reactions, we propose that a previously invoked a Co(I)/Co(III) cycle, common to other similar heterodimerization reactions, might be involved in these reactions as well., Competing Interests: The authors declare no financial interest.

Aim: The aim of this study was to evaluate and compare the flexural strength of Cention N with resin-modified glass-ionomer cement and nanohybrid composite., Materials and Methods: Samples were prepared by filling the stainless steel mold of dimension 2 mm × 2 mm × 25 mm with cement/composite immediately after mixing. Excess flash if any was removed by abrading it with abrasive paper. Then, the specimens were subjected to flexural strength measurement using universal testing machine. The results were then tabulated and statistically analyzed using one-way ANOVA followed by Tukey's multiple post hoc test., Results: The average flexural strength of NT Premium, Vitremer, and Cention N was 90.39 MPa, 46.59 MPa, and 62.88 MPa, respectively. There was a statistically significant difference between NT Premium and Cention N and NT Premium and Vitremer with P = 0.0002 and 0.0001, respectively., Significance: The flexural strength study can help us to choose a material for restoring Class V lesions and can also confirm whether Cention N, a new material, be a definite replacement for amalgam., Conclusion: Cention N has proved to be a better material and can be a replacement for amagam and GIC., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Conservative Dentistry.)

A bioinspired chitosan/vitamin E conjugate (Ch/VES, 1:4) was synthesized, optimized based on chitosan's molecular weight (15, 300 kDa), and was assembled to entrap oxaliplatin (OXPt). 1 H NMR, infrared spectroscopy, chromatography, X-ray photoelectron spectroscopy, X-ray diffraction, drug release, hemolysis, and stability studies were performed to characterize OXPt@Ch/VES micelles. The therapeutic efficacy of the micelles was tested in vitro in ER+/PR+/HER2- and triple-negative sensitive/resistant breast cancer cells, MCF-7 and MDA-MB-231 via cellular uptake, cytotoxicity, nuclear staining, DNA fragmentation, mitochondrial membrane potential, ROS generation, apoptosis, and cell cycle assays and in vivo using 4T1(Luc)-tumor-bearing mice. OXPt@Ch/VES Ms exhibited decreased IC50 towards MCF-7, MDA-MB-231 (sensitive/resistant) than OXPt. OXPt@Ch/VES Ms caused extensive DNA damage, mitochondrial depolarization, apoptosis, and cell-growth arrest (G2/M). OXPt@Ch/VES Ms treatment retarded tumor growth significantly, prolonged survival, and decreased nephrotoxicity than OXPt. The OXPt@Ch/VES Ms could serve as a potential nanomedicine to overcome conventional OXPt-mediated drug resistance/nephrotoxicity in breast cancer., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

This narrative review is aimed to practically review and evaluate the existing evidence and illuminate the effectiveness of physical activity, yoga, and exercise for postpartum and midlife weight management. A comprehensive review was conducted using electronic databases such as PubMed and google scholar using search terms physical activity, exercise, yoga, postpartum, midlife, weight loss, weight reduction, and all the probable terms. This helped in generating evidence-based information and formulating practical physical activity prescriptions to be used by obstetricians, general clinicians, nutritionists, and other allied healthcare personnel. Overweight and obesity in postpartum and midlife women present long-term health risks and complications. Indulging in optimum physical activity comprising exercise and yoga will help in weight management, increasing muscular strength, and endurance thus improving overall health and well-being., Supplementary Information: The online version contains supplementary material available at 10.1007/s13224-022-01627-w., Competing Interests: Conflict of InterestThe authors declare that they do not have any conflict of interest to declare., (© Federation of Obstetric & Gynecological Societies of India 2022.)

Yoga as a movement-based intervention is increasingly considered to improve the motor skills of children with autism spectrum disorder (ASD). However, there is little evidence of the effect of yoga on their motor skills. The current study aims to explore the effect of group yoga program on motor proficiency of children with ASD and feasibility of its inclusion in special schools. Forty-three children with ASD from four special schools were randomized into yoga (n = 23) and control (n = 20) group. A structured yoga program of 45 min for 12 weeks was delivered by trained yoga teachers who also tracked their daily responses. The Bruininks-Oseretsky Test of Motor Proficiency. Second Edition was used to assess both the groups pre- and postintervention. In conclusion, the study highlighted that yoga appears to have a positive impact on the gross motor rather than fine motor proficiency of children with ASD and is feasible to be delivered as group intervention in special schools.

Microorganisms with extracellular electron transfer (EET) capability have gained significant attention for their different biotechnological applications, like biosensors, bioremediation, and microbial fuel cells. Current research affirmed that microbial EET potentially promotes corrosion of iron structures, termed microbiologically influenced corrosion (MIC). The sulfate-reducing (SRB) and nitrate-reducing (NRB) bacteria are the most investigated among the different MIC-promoting bacteria. Unlike extensively studied SRB corrosion, NRB corrosion has received less attention from researchers. Hence, this review focuses on EET by Pseudomonas aeruginosa , a pervasive bacterium competent for developing biofilms in marine habitats and oil pipelines. A comprehensive discussion on the fundamentals of EET mechanisms in MIC is provided first. After that, the review offers state-of-the-art insights into the latest research on the EET-assisted MIC by Pseudomonas aeruginosa . The role of electron transfer mediators has also been discussed to understand the mechanisms involved in a better way. This review will be beneficial to open up new opportunities for developing strategies for combating biocorrosion.

Due to COVID-19, the whole world is undergoing a devastating situation, but treatment with no such drug candidates still has been established exclusively. In that context, 69 diverse chemicals with potential SARS-CoV-2 3CL pro inhibitory property were taken into consideration for building different internally and externally validated linear (SW-MLR and GA-MLR), non-linear (ANN and SVM) QSAR, and HQSAR models to identify important structural and physicochemical characters required for SARS-CoV-2 3CL pro inhibition. Importantly, 2-oxopyrrolidinyl methyl and benzylester functions, and methylene (hydroxy) sulphonic acid warhead group, were crucial for retaining higher SARS-CoV-2 3CL pro inhibition. These GA-MLR and HQSAR models were also applied to predict some already repurposed drugs. As per the GA-MLR model, curcumin, ribavirin, saquinavir, sepimostat, and remdesivir were found to be the potent ones, whereas according to the HQSAR model, lurasidone, saquinavir, lopinavir, elbasvir, and paritaprevir were the highly effective SARS-CoV-2 3CL pro inhibitors. The binding modes of those repurposed drugs were also justified by the molecular docking, molecular dynamics (MD) simulation, and binding energy calculations conducted by several groups of researchers. This current work, therefore, may be able to find out important structural parameters to accelerate the COVID-19 drug discovery processes in the future., Competing Interests: The authors declare no conflict of interests., (© 2021 Elsevier B.V. All rights reserved.)

Introduction . Pseudomonas aeruginosa is now considered as a major bacterial pathogen associated with hospital infections. Frequently, multidrug-resistant (MDR) and extensively drug-resistant (XDR) P. aeruginosa are being encountered. Unusual increase in the P. aeruginosa infections led to the suspicion of outbreaks in the urology ward and cardiothoracic and vascular surgery intensive care unit (CTVS-ICU). Hypothesis. We hypothesize that the localized outbreaks may have originated from environmental sources within the hospital premises. An alternative possibility is the transmission from a previously infected patient or hospital attendant. Understanding the drug-resistance profile and genome characteristics of these clinical samples would determine the likely source of infection and spread. Aim. To perform epidemiological and molecular investigations on the suspected outbreaks of P. aeruginosa in the study centre and identify potential sources of infection. Methodology. Fourteen drug-resistant P. aeruginosa isolated from patients of the urology ward, CTVS-ICU and tap waters collected during the suspected outbreaks were subjected to microbiological and genomic analysis. Comparative genome (CG) analysis of these 14 study genomes with 284 complete P. aeruginosa genomes was performed. Results. Multilocus sequence typing analysis revealed that the isolates belonged to five different sequence types (ST235, ST357, ST639, ST654 and ST1203) and clustered into three distinct groups while two CTVS-ICU isolates remained as singletons. Genome analysis distinguished that the outbreaks in the urology ward and CTVS-ICU are independent, epidemiologically unrelated to each other and with the tap-water isolates. Conclusion. This study highlights the presence of distinct, clonally unrelated, drug-resistant P. aeruginosa within a hospital setting. The genome analysis of the two localized outbreaks revealed their distinct genetic background and phylogenetically unrelated origin. Vigilant screening and effective implementation of infection control measures led to the successful containment of potential environmental reservoirs of P. aeruginosa within the premises.

Aim: Literature reports suggest spirochromanone derivatives exhibit anticancer activity. Methodology: The authors designed and synthesized 18 spirochromanone derivatives ( Csp 1-18 ). The compounds were characterized and evaluated for anticancer activity against human breast cancer (MCF-7) and murine melanoma (B16F10) cell lines. Results: The anticancer activity ranged from 4.34 to 29.31 μm. The most potent compounds, Csp 12 and Csp 18 , were less toxic against the human embryonic kidney (HEK-293) cell line and ∼ two/∼fourfold selective toward MCF-7 than B16F10 in comparison to the reference, BG-45 . Csp 12 caused 28.6% total apoptosis, leading to significant cytotoxicity, and arrested the G2 phase of the cell cycle in B16F10 cells. A molecular docking study of Csp 12 exhibited effective binding at the active site of the epidermal growth factor receptor kinase domain. Conclusion: This study highlights the importance of spirochromanones as anticancer agents.

The classification of bisphenol A (BPA) as an industrial endocrine disruptor has led to a ban of this ubiquitous critical starting material from food and medical applications. Thus, scientists worldwide are researching to develop non-ER binding starting compounds to fulfill unmet market needs. In line with this trending research topic, the current paper highlights the development of tetrazole derivatives bearing a bisphenol structure (TbB) as a novel weak binder or potential inactive to the estrogen receptor (ER) and androgen receptor (AR). The structure and ligand-based approach supported by binding affinity analysis, electrostatic complementarity, ADMET prediction, and in silico studies identified TbBs as privileged substitutes for BPA. Five TbB ligands were successfully synthesized and subjected to biological testing comprising radioligand competitive binding and functional cellular assays. The measured IC 50 value for BPA was found to be 0.24 μM, whereas all the inhibitions were less than 15% for the two TbB ligands, 223-2 and 223-3. As these TbB ligands did not meet the established acceptance criteria of 50% inhibition, they are considered as extremely weak binders to ERα. Steric clashes, the desolvation effect, and the increased total polar surface area (TPSA) of TbB ligands in the hydrophobic binding site are hypothesized to be possible reasons for low binding. Modeling studies complemented by bioassays highlight TbB compounds as privileged prospective BPA replacements. However, more research on TbB ligand toxicity is needed to understand and substantiate that the adverse effects on the hormonal system, for example, via metabolic activation, are not elicited.

Combination chemotherapy produces a superior therapeutic response than monotherapy in cancer. Human serum albumin and a naturally occurring cancer prophylactic/anticancer triterpenoid, oleanolic acid, were conjugated to form self-assembled nanoparticles that entrapped doxorubicin. Dox@HSA-OA NPs were physicochemically characterized for particle size, zeta potential, drug loading, entrapment efficiency, stability, release, and hemocompatibility. The Dox@HSA-OA NPs (particle size. ∼ 140 nm) showed commendable loading (14.6 %), entrapment (59.01%) of Dox. The in vitro cell uptake study using human oral squamous carcinoma (FaDu-HTB-43) and murine melanoma (B16F10) cells indicated a higher cellular association of Dox@HSA-OA NPs than free Dox. The lowest IC 50 of Dox@HSA-OA NPs than Dox against both the cell lines at various time points proved the Dox/HSA-OA-mediated combination chemotherapeutic effect. Dox@HSA-OA NPs demonstrated higher apoptosis and cell cycle arrest (G2/M phase). The Dox@HSA-OA NPs-mediated Dox penetration, cell death/shrinkage were significant in FaDu-HTB-43 spheroids. Dox@HSA-OA NPs showed a better pharmacokinetic profile with increased t 1/2 and Cmax than Dox. The in vivo experiment using B16F10 tumor-bearing mice showed tumor regression, DNA damage, oxidative stress, and apoptosis-induction via the intrinsic pathway to a greater extent following Dox@HSA-OA NPs treatment than Dox. Therefore, the Dox@HSA-OA NPs-mediated combination therapy could be a powerful treatment strategy for solid tumors., (Copyright © 2022 Elsevier B.V. All rights reserved.)

We demonstrate the method of achieving excellent supercapacitance in nitrogen-doped reduced graphene oxide (N-rGO) sheets by controlling the amount of N-content through the use of different ratios of GO and urea during solvothermal synthesis. Here, urea plays a dual role in reducing GO and simultaneously doping nitrogen into the GO flakes forming exfoliated N-rGO sheets. The nitrogen content in N-rGO samples rises with an increase in the amounts of urea and saturates at a value of ∼14% for the GO : urea ratios beyond 1 : 8. The obtained N-rGO sheets with ∼ 5% N-content (obtained for GO : urea ratio of 1 : 3) were demonstrated as excellent supercapacitor materials. Using a 3-electrode setup, the maximum specific capacitance obtained for this sample was 514 F g -1 at a current density of 0.5 A g -1 (mass normalized current). The insights into the origin of this excellent supercapacitive behavior are explained through our results on optimum N-content, the relative amount of different N-environments, defects/disorders, and the degree of reduction of GO. Importantly, a proper stacking of rGO sheets with moderate N-content (∼5-6%) and a moderate amount of defects is the key to achieve high specific-capacitance. Furthermore, our 2-electrode device demonstrates the excellence of our samples with a C sp of 237 F g -1 , a power density of 225 W kg -1 , and an energy density of 6.7 W h kg -1 at 0.5 A g -1 , exhibiting a high cyclic constancy with high capacitive retention of ∼ 82% even after 8000 cycles. Hence, our work provides a way to control the properties of N-rGO in achieving excellent supercapacitive performance.

Agrobiodiversity conservation is vital for achieving sustainability, but empirical studies on the effects of different practices or measures on crop diversity are rare. This study aims to estimate the effects of raising conservation awareness (RCA), building diversity blocks (BDB), and their combination on crop diversity among 240 randomly selected households surrounding the Rupa Lake Watershed in Nepal. Based on descriptive analysis and multiple regression models, the results indicate that the two single measures had no significant effect on the numbers of crop species and varieties grown by households in 2018. However, the combination of RCA and BDB had a significantly positive effect on the number of crop varieties, especially for grain and vegetable crops. Considering that these crops are essential in the daily lives of local people, the results indicate that a strategy that combines both awareness raising and on-farm conservation measures can generate higher crop diversity and better serve the climate-resilient livelihoods of people in mountainous areas., (© The Author(s) 2022.)

Nitrofurantoin (NIT) has long been a drug of choice in the treatment of lower urinary tract infections. Recent emergence of NIT resistant Enterobacteriaceae is a global concern. An ordinal logistic regression model based on PCR amplification patterns of five genes associated with NIT resistance (nfsA, nfsB, ribE, oqxA, and oqxB) among 100 clinical Enterobacteriaceae suggested that a combination of oqxB, nfsB, ribE, and oqxA is ideal for NIT resistance prediction. In addition, four Escherichia coli NIT-resistant mutants were in vitro generated by exposing an NIT-susceptible E. coli to varying concentrations of NIT. The in vitro selected NIT resistant mutants (NI2, NI3, NI4 and NI5) were found to have mutations resulting in frameshifts, premature/lost stop codons or failed amplification of nfsA and/or nfsB genes. The in vitro selected NI5 and the transductant colonies with reconstructed NI5 genotype exhibited reduced fitness compared to their parent strain NS30, while growth of a resistant clinical isolate (NR42) was found to be unaffected in the absence of NIT. These results emphasize the importance of strict adherence to prescribed antibiotic treatment regimens and dosage duration. If left unchecked, these resistant bacteria may thrive at sub-therapeutic concentrations of NIT and spread in the community., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2021 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

In this article, we propose high-performance colorimetric detection of Hg +2 using silver nanoprisms. The spherical and triangular AgNPs were synthesized using varied concentration of NaBH4. Pristine AgNPs without any further modification were used for the detection of various metal ions including Hg 2+ , Pb 2+ , Cl - , Cd 2+ , Co 2+ , Cu 2+ , Ba 2+ , Pb 2+ , Cr 3+ , Cr₂O 2- 7 , Fe 2+ , Fe 3+ etc. AgNPs were not only selective in detecting the ions of Cl - and Hg +2 ions but also highly sensitive. Minimum detection limit was observed to be as low as 10 -7 ppm for both Hg +2 and Cl - . Water samples collected from various locations detected for the presence of various heavy metals. Silver nanoprisms owing to their surface plasmon resonance exhibit highly selective tendency towards detection against Hg +2 .

Bacterial keratitis (BK) is a leading cause of visual impairment. The fluoroquinolone antibiotic moxifloxacin (Mox), being highly water-soluble, suffers from poor corneal penetration leading to unsatisfactory therapeutic outcomes in BK. Here, we prepared Mox-loaded co-polymeric nanoparticles (NPs) by entrapping the drug in co-polymeric NPs constituted by the self-assembly of a water-soluble copolymer, poly(ethylene glycol)-b-p(hydroxypropyl) methacrylamide (mPH). The polymer (mPH) was prepared using a radical polymerization technique at different mPEG: HPMA ratios of 1:70/100/150. The polymer/nanoparticles were characterized by GPC, CAC, DLS, SEM, XRD, DSC, FTIR, % DL, % EE, and release studies. The ex vivo muco-adhesiveness and corneal permeation ability were judged using a texture analyzer and Franz Diffusion Cells. In vitro cellular uptake, cytotoxicity, and safety assessment were performed using HCE cells in monolayers, spheroids, and multilayers in transwells. The DOE-optimized colloidal solution of Mox-mPH NPs (1:150) displayed a particle size of ~116 nm, superior drug loading (8.3%), entrapment (83.2%), robust mucoadhesion ex vivo, and ocular retention in vivo (~6 h) (judged by in vivo image analysis). The non-irritant formulation, Mox-mPH NPs (1:150) (proven by HET-CAM test) exhibited intense antimicrobial activity against P. aeruginosa, S. pneumoniae, and S. aureus in vitro analyzed by live-dead cells assay, zone of inhibition studies, and by determining the minimum inhibitory and bactericidal concentrations. The polymeric nanoparticles, mPH (1:150), decreased the opacity and the bacterial load compared to the other treatment groups. The studies warrant the safe and effective topical application of the Mox-mPH NPs solution in bacterial keratitis., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Histone deacetylase 3 (HDAC3) is one of the most promising targets to develop anticancer therapeutics. In continuation of our quest for selective HDAC3 inhibitors, a series of small molecules having o-hydroxy benzamide as the novel zinc binding group (ZBG) has been introduced for the first time that can be able to produce good HDAC3-selectivity over other HDACs. The most promising HDAC3 inhibitors, 11a and 12b, displayed promising in vitro anticancer activities with less toxicity to normal kidney cells. These compounds significantly upregulate histone acetylation and induce apoptosis with a G2/M phase arrest in B16F10 cells. Compound 11a exhibited potent antitumor efficacy in 4T1-Luc breast cancer xenograft mouse model in female Balb/c mice. It also showed significant tumor growth suppression with no general toxicity and extended survival rates post-tumor resection. It significantly induced higher ROS generation, leading to apoptosis. No considerable toxicity was noticed in major organs isolated from the compound 11a-treated mice. Compound 11a also induced the upregulation of acH3K9, acH4K12, caspase-3 and caspase-7 as analyzed by immunoblotting with treated tumor tissue. Overall, HDAC3 selective inhibitor 11a might be a potential lead for the clinical translation as an emerging drug candidate., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A series of facial -Re(CO) 3 -based acyclic complexes (1-3) possessing N∩O bis-chelating ligands and a triphenylphosphine oxide donor was synthesized and characterized. The most interesting structural feature of these complexes is that both the coordinated ligands are functionalized with external phenyl rings. Single crystal X-ray diffraction analysis confirms that each molecule demonstrates a variety of intermolecular supramolecular interactions via the external phenyl rings. All the complexes displayed strong absorption ( ε = 14 000-40 000 M -1 cm -1 ) over wide visible region (400-600 nm). Due to the interesting structural and photophysical properties of the complexes, a satisfactory DNA binding ability was observed. The binding of the complexes with DNA grooves was confirmed by a significant increase in the absorption intensities of the complexes in the visible region, absorption enhancement of DNA and circular dichroism.

Carbohydrate functionalized polymers or Glycopolymers have earned a great deal of interest in recent times for their potential biomedical applications. In the present study, a mannose containing glycopolymer was synthesized by cyclopolymerization of malonic acid derivative using second generation Hoveyda Grubbs' catalyst. Post-polymerization modification was done to install a propargyl moiety. Finally, functionalization of the propargylated polymer with 2-azidoethyl mannoside using azide-alkyne "click chemistry" furnished the target glycopolymer which was successfully characterized using NMR, FT-IR, mass spectroscopy and advanced polymer chromatography. The glycopolymer was found to self-assemble into capsule and spherical shape in water and DMSO respectively and these morphologies were observed through SEM and TEM. Upon interaction with Con A, the mannose containing glycopolymer showed an increment in aggregation induced fluorescence with increasing concentration of the lectin. In vitro cytotoxicity studies on MCF 7 cell line showed 90% cell viability up to glycopolymer concentration of 500 μg/mL., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Delivery of combination chemotherapeutic agents to the tumor via nanovesicles has the potential for superior tumor suppression and reduced toxicity. Herein, we prepare a block copolymer (mPH-RA) composed of methoxy-poly(ethylene glycol) (mPEG), b-poly(N-(2 hydroxypropyl) methacrylamide) (pHPMA), and all-trans retinoic acid (ATRA) by conjugating ATRA to the pre-formed copolymer, mPEG-b-pHPMA(mP-b-pH). Doxorubicin-loaded micelles, Dox@mP-b-pH, and Dox@mPH-RA were characterized by determining particle size, zeta potential, % DL, EE, Dox release, hemolysis study, and by DSC. The Dox@mPH-RA micelles (mPH-RA: Dox ratios of 10:0.5-2) displayed nano-size (36-45 nm), EE. 26-74%, and DL. 2.9-5.6%. Dox@mPH-RA micelles displayed the highest penetrability and cytotoxicity than free Dox and Dox@mP-b-pH micelles in breast cancer cell lines. Dox@mPH-RA exhibited the highest induction of apoptosis (94.1 ± 3%) than Dox (52.1 ± 4.5%), and Dox@mP-b-pH (81.7 ± 3%), and arrested cells in the highest population in G2 and S phase. Dox@mPH-RA increased the t 1/2 and C max of Dox and demonstrated improved therapeutic efficacy and highest Dox distribution to the tumor. The Dox@mPH-RA increased the levels of apoptosis markers, caspase 3, 7, Ki-67, and caused the highest DNA fragmentation. The presence of RA improved the micelles' physicochemical properties, Dox-loading ability, and the therapeutic potential in Dox@mPH-RA via the combination therapeutic strategy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Microorganisms present in the guts are the causative agents for various diseases in humans. More and more studies are correlating such diseases and the responsible microorganism. The Gram-positive bacterium Ruminococcus gnavus (R. gnavus) has been identified to be responsible for symptoms of Crohn's disease. R. gnavas produces a glucorhamnan polysaccharide and it is postulated that this polysaccharide induces inflammatory response through toll-like receptor 4 (TLR4). The current manuscript describes the chemical synthesis of the pentasaccharide repeating unit of the O-polysachharide from R. gnavus. The major challenge associated with this particular synthesis is the presence of two consecutive 1,2-cis glucose units. The target oligosaccharide is achieved through a linear strategy from commercially available sugars through rational protecting group manipulation. 1,2-cis glycosylation of glucose through remote participation of acyl group at the 6-O position is used successfully with excellent yield. In both cases, sole 1,2-cis products are obtained at -20 °C through the activation of thioglycosides., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Nutrient source and transport study in tropical creeks adjacent to megacities are sparse on a regional and global scale. High-frequency chemical data collected during 2017-2018 in the Thane creek system, the largest micro-tidal urbanized creek in Asia, were analysed to assess the chemical water quality, with its linkage to different hydrological stages (southwest monsoon, post- and pre-monsoon) and ongoing anthropogenic activities. Cluster analysis indicates typical zonation between creek outflow and nearshore waters with distinctive physicochemical properties. The creek outflow upholds substantial amounts of nutrient and suspended sediment due to turbid water movement from the ephemeral mudflats and anthropogenic dredging. The year-round hyper-turbid condition in the bottom water triggers the addition of disproportionate nutrients (9% dissolved inorganic nitrogen (DIN) and 14% reactive phosphorous (PO 4 3- ) in the outflow region. The DIN and PO 4 3- removal up to 10 and 35%, respectively, occurs in the nearshore region; sedimentation, which acts as a sinking interface for nitrogen and phosphorous, also causes shifting in their limiting conditions. The hyper-turbid condition causes removal of dissolved silicate (DSi) by 5% in the entire region. Ammonium (NH 4 + ) is mainly sourced from the sewage in outflow waters and efficiently mineralized. Chemical indexing of water highlights that the bottom water column remained un-supportive to the balanced ecology. The findings of this study have implications for other tropical creek-estuary concerning management strategies against inadequate flushing. The stalled nutrient export affected balance ecology in tropical Thane creek, which need attention in order to accurately understand the impact on adjacent marine environment and to form effective mitigation policies., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Brucella anthropi is a Gram-negative, aerobic, motile, oxidase-positive, non-fermentative Alphaproteobacteria belonging to the family Brucellaceae. It is most commonly found in soil but is an emerging, opportunistic, nosocomial human pathogen. The objective of this study was to understand the genome features of a drug-resistant B. anthropi (SOA01) isolated from a blood culture of a 4-day-old neonate and to determine its antimicrobial resistance and pathogenic potential., Methods: Hybrid genome assembly of B. anthropi strain SOA01 was generated using quality-trimmed short Illumina and long MinION reads. Identification and antimicrobial susceptibility profile were determined by MALDI-TOF, in silico ribosomal multilocus sequence typing (rMLST) and VITEK®2, respectively. PATRIC webserver and VFDB were used to identify antimicrobial resistance (AMR), virulence factor (VF) and transporter genes., Results: Multidrug-resistant B. anthropi strain SOA01 has a genome of 4 975 830 bp with a G+C content of 56.29%. Several AMR, VF and transporter genes were identified in the genome. Antimicrobial susceptibility testing revealed resistance to different classes of antibiotics in strain SOA01., Conclusion: Brucella anthropi SOA01 is a multidrug-resistant strain. Several AMR and VF genes were identified in the genome, revealing the potential threat posed by this pathogen. The genome data generated in this study are likely to be useful in better understanding its AMR mechanisms, pathogenic potential and successful adaptation from its primary habitat of soil to the human system. Since it is often misidentified as Brucella melitensis or Brucella suis, genome characterisation and detailed understanding of its biology are crucial., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

A series of novel linker-less benzamides with different aryl and heteroaryl cap groups have been designed, synthesized, and screened as potent histone deacetylase (HDAC) inhibitors with promising anticancer activity. Two lead compounds 5e and 5f were found as potent and highly selective HDAC3 inhibitors over other Class-I HDACs and HDAC6. Compound 5e bearing a 6-quinolinyl moiety as the cap group was found to be a highly potent HDAC3 inhibitor (IC 50  = 560 nM) and displayed 46-fold selectivity for HDAC3 over HDAC2, and 33-fold selectivity for HDAC3 over HDAC1. The synthesized compounds possess antiproliferative activities against different cancer cell lines and significantly less cytotoxic to normal cells. Molecular Docking studies of compounds 5e and 5f reveal a similar binding mode of interactions as CI994 at the HDAC3 active site. These observations agreed with the in vitro HDAC3 inhibitory activities. Significant enhancement of the endogenous acetylation level on H3K9 and H4K12 was found when B16F10 cells were treated with compounds 5e and 5f in a dose-dependent manner. The compounds induced apoptotic cell death in Annexin-V/FITC-PI assay and caused cell cycle arrest at G2/M phase of cell cycle in B16F10 cells. These compounds may serve as potential HDAC3 inhibitory anticancer therapeutics., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Human granulocyte colony stimulating factor (hG-CSF) is an expensive hematopoietic growth factor that is clinically used in human for the treatment of neutropenia in diseases such as AIDS, aplastic anemia, myelodysplastic syndrome and congenital or chemotherapy-induced neutropenia. Here, through a computational biology approach, we show that human stem cell factor (hSCF) could be a better fusion partner than human thyroid peroxidase (hTPO), human erythropoietin (hEPO) and human interleukin-3 (hIL3) for co-expression with hG-CSF. Molecular modeling of hG-CSF-hSCF fusion protein with hG-CSF and hSCF receptors showed that binding of fusion protein with human granulocyte colony stimulating factor receptor (hG-CSFR) did not inhibit its binding to human stem cell factor receptor (hSCFR) and vice versa. To validate the results, coding sequences of hG-CSF and hSCF were cloned and co-expressed as fusion protein and their bioactivity was evaluated on hG-CSF responsive 3T3 cell line. The fused expression vector expressed recombinant hG-CSF-hSCF upon IPTG-induction, as revealed by real-time polymerase chain reaction (RT-PCR), sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis. Bioactivity analysis confirmed that rhG-CSF-hSCF protein had higher bioactivity than hG-CSF. Thus, hSCF could be a good fusion partner for hG-CSF and its co-expression as hG-CSF-hSCF may offer an alternative to individual use of two hematopoietic factors in clinics. Future studies should determine the purification strategies, folding status and mechanism of action of the recombinant proteins. Communicated by Ramaswamy H. Sarma.

Carbohydrate-protein and carbohydrate-carbohydrate interactions are very important for various biological processes. Although the magnitude of these interactions is low compared to that of protein-protein interaction, the magnitude can be boosted by multivalent approach known as glycocluster effect. Nanoparticle platform is one of the best ways to present diverse glycoforms in multivalent manner and thus, the field of glyconanotechnology has emerged as an important field of research considering their potential applications in diagnostics and therapeutics. Considerable advances in the field have been achieved through development of novel techniques, use of diverse metallic and non-metallic cores for better efficacy and application of ever-increasing number of carbohydrate ligands for site-specific interaction. The present review encompasses the recent developments in the area of glyconanotechnology and their future promise as diagnostic and therapeutic tools., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Hemorrhage is a leading cause of preventable death in both military combat and civilian accidents. To overcome these challenges, an affordable and effective bandage is must required substance. A novel strategy is reported for developing chitosan-casein (CC) based self-assembled nanofibrous polyelectrolyte complex (PEC) for rapid blood clotting. The amide group (1630 cm -1 ) and phosphate group (910 cm -1 ) of chitosan-casein can form PEC at pH 8.2 ± 0.2. The PECs contain intertwined nanofibers (≤100 nm diameter) with a high surface area. Increasing chitosan percentage from 30% (CC30) to 50% (CC50) or 70% (CC70) results, increase in zeta potential of PEC from -9.14 ± 3.3 to 7.46 ± 3.7 and 14.8 ± 3.3 mV, respectively. Under in vitro conditions, the CC30, CC50, and CC70 PECs allow platelet adhesion and rapidly absorbs blood fluid to form mechanically stable blood clots within 9 ± 3, 16 ± 3, and 30 ± 4 s, respectively, which are better than Celox™ (90 ± 3 s). In vivo application of PEC (CC50) causes clotting within 37 ± 6 s of large (1 cm) arterial incision in rabbit models. The PEC is biocompatible with promising hemostatic efficiency. This is the first report of nanofibrous PEC from chitosan and casein for rapid clotting, to the best of our knowledge., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Motivation: We discover that maximality of information content among intervals of Tandem Repeats (TRs) in animal genome segregates over taxa such that taxa identification becomes swift and accurate. Successive TRs of a motif occur at intervals over the sequence, forming a trail of TRs of the motif across the genome. We present a method, Tandem Repeat Information Mining (TRIM), that mines 4k number of TR trails of all k length motifs from a whole genome sequence and extracts the information content within intervals of the trails. TRIM vector formed from the ordered set of interval entropies becomes instrumental for genome segregation., Results: Reconstruction of correct phylogeny for animals from whole genome sequences proves precision of TRIM. Identification of animal taxa by TRIM vector upon feature selection is the most significant achievement. These suggest Tandem Repeat Interval Pattern (TRIP) is a taxa-specific constitutional characteristic in animal genome., Availabilityand Implementation: Source and executable code of TRIM along with usage manual are made available at https://github.com/BB-BiG/TRIM., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: M. morganii is a gram-negative, non-lactose fermenting and an opportunistic pathogen frequently associated with nosocomial infections. Although first isolated in 1906 from a pediatric fecal sample, not many M. morganii isolates have been sequenced. The objective of this work is to determine the complete genome sequence of an XDR M. morganii strain (SMM01) isolated from the urine of a patient with urinary and fecal incontinence and to characterize its antimicrobial resistance profile., Data Description: Here, we report the complete genome sequence of M. morganii SMM01 generated from the hybrid assembly of Illumina HiSeq X and Nanopore MinION reads. The assembly is 100% complete with genome size of 39,30,130 bp and GC content of 51%. Genomic features include 3617 CDS, 18 rRNAs, 78 tRNAs, 4 ncRNAs and 60 pseudogenes. Antimicrobial resistance profile was characterized by the presence of genes conferring resistance to aminoglycosides, β-lactams, fluoroquinolones, chloramphenicol, and tetracyclines. Secondary metabolite biosynthetic gene clusters like NRPS, T1PKS, thiopeptide, beta-lactone, and bacteriocin were identified. The genome data described here would be the first complete genome of an Indian M. morganii isolate providing crucial information on antimicrobial resistance patterns, paving the way for further comparative genome analyses., (© 2021. The Author(s).)

Chemical synthesis of the tetrasaccharide repeating unit of the O-antigen from E. coli O74 is accomplished by a convergent [2 + 2] block synthesis strategy. The challenging rare D-Fuc3NAc has been prepared using DTBP and TIPST mediated deoxygenation reaction. Other monosaccharide synthons are prepared through rational protecting group manipulations and the stereoselective glycosylations are achieved either by the activation of thioglycoside or glycosyl trichloroacetimidate. The target tetrasaccharide is made in the form of its 2-aminoethyl glycoside to facilitate further glycoconjugate formation without affecting the anomeric stereochemistry., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In the present study, polymeric micelles constituted of N-(2-hydroxypropyl)methacrylamide (HPMA) and methoxypoly(ethylene glycol) (mPEG)-based copolymer, mPEG-b-HPMA was studied for the delivery of an anticancer drug, doxorubicin (DOX) by physically loading the drug into its core. A series of mPEG-b-HPMA copolymers of different molecular weights (MWs, ∼4000-25,000 Da) by using various initiator: monomer feed ratios (1:25/75/125/175) were synthesized by radical polymerization technique. The DOX-loaded micelles were prepared at different drug to polymer ratios by thin film hydration method. Block copolymers were structurally characterized by gel permeation chromatography (GPC), 1 H-NMR spectroscopy, fourier transform infrared spectroscopy (FTIR), and critical micelles concentration studies. The DLS and SEM studies indicated that the micelles were spherical with diameters ∼20-100 nm. The DOX-loaded mPEG-b-HPMA micelles, P6-M1, prepared by the polymer synthesized using initiator: monomer feed ratios of 1:175 and at polymer to drug ratios of 10:1 exhibited low particle sizes (∼46.8 nm), highest drug loading and encapsulation efficiencies (5.6 %, and 63.3 %, respectively) compared to the other tested formulations. Confocal microscopy study indicated that the P6-M1 was taken up by breast cancer cell lines, 4T1, MCF-7, and MDA-MB-231in a time-dependent manner. P6-M1 displayed lower half maximal inhibitory concentration (IC 50 ) compared to free drug in all tested treatment durations compared to free DOX. P6-M1 was safe in hemolysis studies with sustained DOX residence in circulation compared to free DOX. The results indicated that mPEG-b-HPMA could be utilized to load DOX effectively, and the optimized nano-micelles, P6-M1 could serve as a promising nanomedicine to treat breast cancer., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The acetylation of histone and non-histone proteins has been implicated in several disease states. Modulation of such epigenetic modifications has therefore made histone deacetylases (HDACs) important drug targets. HDAC3, among various class I HDACs, has been signified as a potentially validated target in multiple diseases, namely, cancer, neurodegenerative diseases, diabetes, obesity, cardiovascular disorders, autoimmune diseases, inflammatory diseases, parasitic infections, and HIV. However, only a handful of HDAC3-selective inhibitors have been reported in spite of continuous efforts in design and development of HDAC3-selective inhibitors. In this Perspective, the roles of HDAC3 in various diseases as well as numerous potent and HDAC3-selective inhibitors have been discussed in detail. It will surely open up a new vista in the discovery of newer, more effective, and more selective HDAC3 inhibitors.

Total synthesis of the pentasaccharide repeating unit of the OPS from Halomonas ventosae RU5S2EL is accomplished through a [3+2] block strategy. Picoloyl-induced hydrogen-bond-assisted aglycon delivery (HAD) is used for two consecutive 1,2- cis -l-rhamnosylations, and remote participation is used for α-selective glucosylation. The choice of 2-aminoethyl glycoside at the reducing end is opted for, leaving the scope for further glycoconjugate formation without hampering the reducing-end stereochemistry.

A series of thirty-one novel 7-(5-((amino)-methyl)-thiophen-2-yl)-spiro-[chroman-2,4'-piperidin]-4-one hydrochloride analogues (Cst 1 - 31) have been designed, synthesized and characterized by 1 H NMR, 13 C NMR and MS spectral analysis. Here, we evaluated the anticancer potential and biological results of low-molecular-weight bridgehead oxygen and nitrogen-containing spirochromanones on proliferation and apoptosis of the human breast cancer cell line (MCF-7) and Murine melanoma (B16F10). The anticancer activity ranged from 2.9 to 35.0 µM. The most potent compounds Cst-22, Cst-24 and Cst-31 were found to be less toxic against human embryonic kidney (HEK-293) cell lines. Cst-24 and Cst-31 were found to be causing significant cytotoxicity through apoptotic cell death and also G2 phase arrest of cell cycle in B16F10 cells. In-silico ADME prediction stidies of the titled compounds were found within the rules outlined, and these compounds may not face any pharmacokinetic associated issues in the mere future upon developmental stage. These conjugates may serve as a lead for the discovery of potential anticancer drug candidate with better therapeutic profile., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Geomicrobiological details of the interactions between groundwater microbiome (GWM) and arsenic (As)-rich aquifer sediment of Bengal basin was investigated through microcosm incubations. Role of key microorganisms and their specific interactions with As-bearing minerals was demarcated under organic carbon- amended and -unamended conditions. Acinetobacter (50.8 %), Brevundimonas (7.9 %), Sideroxydans (3.4 %), Alkanindiges (3.0 %) dominated the GWM. The microbiome catalysed considerable alterations in As-bearing mineral [Fe-(hydr)oxide and aluminosilicate] phases resulting in substantial changes in overall geochemistry and release of As (65 μg/L) and Fe (118 μg/L). Synergistic roles of autotrophic, NH 4 + -oxidizing Archaea (Thaumarchaeota) and chemoheterotrophic bacteria (Stenotrophomonas, Pseudomonas, Geobacter) of diverse metabolic abilities (NH 4 + -oxidizing, NO 3 - , As/Fe-reducing) were noted for observed changes. Organic carbon supported enhanced microbial growth and As mobilization (upto 403.2 μg As/L) from multiple mineral phases (hematite, magnetite, maghemite, biotite, etc.). In presence of high organic carbon, concerted actions of anaerobic, hydrocarbon-utilizing, As-, Fe-reducing Rhizobium, fermentative Escherichia, anaerobic Bacillales, metal-reducing and organic acid-utilizing Pseudomonas and Achromobacter were implicated in altering sediment mineralogy and biogeochemistry. Increase in abundance of arrA, arsC, bssA genes, and dissolution of Fe, Ca, Mg, Mn confirmed that dissimilatory-, cytosolic-As reduction, and mineral weathering fuelled by anaerobic (hydro)carbon metabolism are the predominant mechanisms of As release in aquifers of Bengal basin., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The draft genome of pandrug-resistant Pseudomonas aeruginosa strain SPA03, which belongs to global high-risk sequence type 357 (ST357) and was isolated from a patient with benign prostatic hyperplasia, is presented in this report. The genome assembly was generated by combining short-read Illumina HiSeq-X Ten and long-read Oxford Nanopore Technologies MinION sequence data using the Unicycler assembler.

Objectives: The genus Burkholderia comprises rod-shaped, non-spore-forming, obligately aerobic Gram-negative bacteria that is found across diverse ecological niches. Burkholderia contaminans, an emerging pathogen associated with cystic fibrosis, is frequently isolated from contaminated medical devices in hospital settings. The aim of this study was to understand the genomic characteristics, antimicrobial resistance profile and virulence determinants of B. contaminans strain SBC01 isolated from the eye of a patient hit by a cow's tail., Methods: A hybrid sequence of isolate SBC01 was generated using Illumina HiSeq and Oxford Nanopore Technology platforms. Unicycler was used to assemble the hybrid genomic sequence. The draft genome was annotated using the NCBI Prokaryotic Genome Annotation Pipeline. Antimicrobial susceptibility testing was performed by VITEK®2. Antimicrobial resistance and virulence genes were identified using validated bioinformatics tools., Results: The assembled genome size is 8 841 722 bp with a G+C content of 66.33% distributed in 19 contigs. Strain SBC01 was found to possess several antimicrobial resistance and efflux pump genes. The isolate was susceptible to tetracyclines, meropenem and ceftazidime. Many genes encoding potential virulence factors were identified., Conclusion: Burkholderia contaminans SBC01 belonging to sequence type 482 (ST482) is a multidrug-resistant strain containing diverse antimicrobial resistance genes, revealing the risks associated with infections by new Burkholderia spp. The large G+C-rich genome has a myriad of virulence factors, highlighting its pathogenic potential. Thus, while providing insights into the antimicrobial resistance and virulence potential of this uncommon species, the present analysis will aid in understanding the evolution and speciation in the Burkholderia genus., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The present study highlights an analytical hybrid scheme consisted of a shift of variables and finite integral transform for analysing a local thermal non-equilibrium (LTNE) bioheat model. This model can have utilised to be a betterment of prediction of the temperature field in the localised hyperthermia therapy (LHT) for the treatment of cancer patients. As the hyperthermia treatment is only the application in living tissues, an appropriate initial condition for the therapeutic thermal response is proposed instead of a constant temperature taken in the previous studies based on the 1-D heat flow. The present analysis suggests the therapeutic exposure time of 7776.8s (2.16 h) with constant heat flux and the exposure time of 10969.9s (3.06 h) with a sinusoidal heat flux within the usual temperature range of the hyperthermia (in a combination of thermal ablation and medium temperature hyperthermia) to be more effective in the treatment protocol. The presented results show that fatal injuries (tissue trauma, thermal burn, etc.) of internal organs might be possible to avoid by the current therapeutic condition. Therefore, this study may nullify the adverse effect of the existing model with the constant heating and consequently, the repercussion of the several therapeutic variables is to estimate with the development of a thermal profile for the suitability of a therapeutic condition. On the other hand, the present study well matches with the published analysis in case of both the theoretical and experimental (live tissues of the pig due to unavailability of real-time data on the human body) studies and it found the maximum deviation of the thermal response as 2.26% and 2.66%, respectively.

Aim of the Study: To compare the microleakage in teeth restored using silver diamine fluoride (SDF) and dental varnish under amalgam restoration., Materials and Methods: Twenty premolar teeth were used in the study. Class I cavity was prepared and restored using silver amalgam. In group I, the dental varnish was used under restoration, and in group II, the SDF was used. All samples were tested for microleakage using methylene blue assay and evaluated under stereomicroscope., Results: Group I samples showed minimal microleakage when compared with group II with a p value <0.002., Conclusion: Silver diamine fluoride would not be an alternative to dental varnish., How to Cite This Article: Hiremath G, Naik B. Comparison of Microleakage under Amalgam Restoration: An In Vitro Study. Int J Clin Pediatr Dent 2021;14(3):340-341., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2021; Jaypee Brothers Medical Publishers (P) Ltd.)