A two-dimensional Cu-based nanosheet producing formic acid via glycerol electro-oxidation in alkaline water.

The sluggishness of the complementary oxygen evolution reaction (OER) is reckoned as one of the major drawbacks in developing an energy-efficient green hydrogen-producing electrolyzer. An array of organic molecule oxidation reactions, operational at a relatively low potential, have been explored as a substitute for the OER. Glycerol oxidation reaction (GOR) has emerged as a leading alternative in this context. Additionally, the GOR generates several value-added organic compounds following oxidation that enhance the cost viability of the overall electrolysis reaction. In this study, a low-cost, room temperature operable, and energy-efficient synthetic methodology has been developed to generate unique two-dimensional CuO nanosheets (CuO NS). This CuO NS material was embedded on a carbon paper electrode, which showcased excellent glycerol electro-oxidation performance operational at a moderately low applied potential. Formic acid is the major product of this CuO NS-driven GOR (Faradaic efficiency ~80%), as it is formed primarily via the glyceraldehyde oxidation pathway. This CuO NS material was also active for oxidizing other abundant alcohols like ethylene glycol and diethylene glycol, albeit at a relatively poor efficiency. Therefore, this robust CuO NS material has displayed the potential to be used in large-scale electrolyzers functioning with HER/GOR reactions.

Cissus Extracts in Dentistry: A Comprehensive Review on its Untapped Potential.

Natural products have received a lot of attention in a variety of medical sectors, including dentistry. Cissus, a flowering plant genus, has long been used for its therapeutic benefits. The purpose of this review is to thoroughly investigate the possibilities of Cissus extracts in dentistry. To that end, we used specific selection criteria for the selection of pertinent scientific articles published in the scientific information databases of PubMed, Web of Science, Google Scholar, Scopus, and ProQuest. We found that the diverse array of bioactive compounds found in varied species of Cissus holds promise for applications ranging from oral wound healing to periodontal health. This review summarizes known studies on antibacterial, anti-inflammatory, and tissue-regenerative characteristics of Cissus extracts, shedding light on their potential significance in modernizing modern dental practices. It exerts that Cissus extracts have the potential to supplement established dentistry therapies by providing all-natural remedies for a variety of oral health conditions.

Production of hydrogen from alcohols via homogeneous catalytic transformations mediated by molecular transition-metal complexes.

Hydrogen obtained from renewable sources such as water and alcohols is regarded as an efficient clean-burning alternative to non-renewable fuels. The use of the so-called bio-H2 regardless of its colour will be a significant step towards achieving global net-zero carbon goals. Challenges still persist however with conventional H2 storage, which include low-storage density and high cost of transportation apart from safety concerns. Global efforts have thus focussed on liquid organic hydrogen carriers (LOHCs), which have shown excellent potential for H2 storage while allowing safer large-scale transformation and easy on-site H2 generation. While water could be considered as the most convenient liquid inorganic hydrogen carrier (LIHC) on a long-term basis, the utilization of alcohols as LOHCs to generate on-demand H2 has tasted instant success. This has helped to draw a road-map of futuristic H2 storage and transportation. The current review brings to the fore the state-of-the-art developments in hydrogen generation from readily available, feed-agnostic bio-alcohols as LOHCs using molecular transition-metal catalysts.

Aggregation-Induced Fluorescence Upconversion of Pyrene under Low Fluence: In Solutions and Polymeric Nanoparticles.

In this study, aggregation-induced photon upconversion (iPUC) is demonstrated in the small polyaromatic molecule, pyrene. In binary-solvent mixtures, water, which induces the aggregation of polyaromatic molecules, assisted in triplet-triplet annihilation-based upconversion. No upconverted emission was observed in a dry solvent. Although upconverted emission in the absence of a triplet sensitizer was assigned to pyrene-aggregate-induced sensitization, the presence of a triplet sensitizer enhanced the upconversion efficiency. This experimental finding was further simulated to explore the possibility of iPUC in the condensed-phase polymer matrix. We studied 2-aminoethyl methacrylate hydrochloride-polystyrene copolymer nanoparticles embedded with the molecular upconversion system. The nanoparticle iPUC agreed with the proposition that water domains were present in polymer nanoparticles and helped aggregate pyrene in the host polymer. Despite the low systemic upconversion efficiency, this study provides a method for achieving fluorescence upconversion in relatively simple systems.

Dysregulation of DNA epigenetic modulators during prostate carcinogenesis in an eastern Indian patient population: Prognostic implications.

The role of epigenetic alteration in prostate cancer pathogenesis was reported. We aimed to analyze dysregulation of DNA methylase (DNA methyl transferase/DNMT) and demethylase (ten eleven translocase/TET) and the associated interplay between them during prostate tumorigenesis. Promoter methylation and RNA/protein expression of selected DNMT and TETs were analysed in normal prostate, benign prostatic hyperplasia (BPH), and prostate cancer (PCa). Genomic 5-hydroxymethylcytosine (5hmC) level was detected and correlated with DNMT and TET proteins. Clinicopathological association of molecular data was done. Our data revealed a very low frequency of promoter methylation for DNMT1 (5-3% and high frequency for TET1 (22-38%), TET2 (68-90 %), and TET3 (43-32 %) in BPH and PCa. The promoter methylation of DNMT1 (p = 0.019) showed a significantly decreasing trend, while that of TET1 (p = 0.0005) and TET2 (p < 0.0001) showed an increasing trend from normal prostate to BPH to PCa, indicating their epigenetic dysregulation during prostate tumorigenesis. RNA/protein overexpression of DNMT1 and reduced expression of TET1 and TET2 in PCa compared to BPH were associated with the promoter methylation status of genes. The 5hmC level was significantly lower in PCa than in BPH and correlated negatively with DNMT1 but positively with TET1 and TET2 proteins, suggesting dysregulation of DNA methylase and de-methylase activities during prostate tumorigenesis. Lastly, tumors having methylated TET1 and TET2 promoters showed advanced clinicopathological features (a higher PSA level/Gleason score) and increased risk of bone metastasis. In conclusion, DNMT1 upregulation and epigenetic silencing of TET1 and TET2 was seen during PCa development. TET1 and TET2 promoter methylation has prognostic importance.

An In-silico Approach to Design and Validate siRNA against Monkeypox Virus.

INTRODUCTION: The monkeypox virus has emerged as an uncommon zoonotic infection. The recent outbreak of MPXV in Europe and abroad in 2022 presented a major threat to individuals at risk. At present, no specific MPXV vaccinations or medications are available. METHODS: In this study, we predicted the most effective siRNA against the conserved region of the MPXV and validated the activity by performing molecular docking studies. RESULTS: Ultimately, the most efficient siRNA molecule was shortlisted against the envelope protein gene (B6R) based on its toxicity, effectivity, thermodynamic stability, molecular interaction, and molecular dynamics simulations (MD) with the Human Argonaute 2 protein. CONCLUSION: Thus, the strategy may offer a platform for the development of potential antiviral RNA therapeutics that target MPXV at the genomic level.

HAGLR, A Long Non-coding RNA of Potential Tumor Suppressive Function in Clear Cell Renal Cell Carcinoma: Diagnostic and Prognostic Implications.

Research works suggested the role of long non-coding RNAs (lncRNAs) in pathogenesis of clear cell renal cell carcinoma (ccRCC). lncRNA HAGLR is studied in several malignancies, but not in ccRCC. From The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) dataset, we analyzed molecular alterations of HAGLR and constructed a competitive endogenous RNA (ceRNA) network with related miRNAs and mRNAs. Gene Ontology analysis was done to identify important pathways enriched with HAGLR recovered mRNAs. Clinical importance of HAGLR and related mRNAs was assessed and, the impact of selected mRNA-encoding genes on tumor immune infiltration was studied using TIMER. HAGLR expression was reduced in ccRCC than in normal kidneys, and correlated significantly with gene promoter methylation. Low HAGLR level in tumors showed diagnostic potency, and was associated with clinicopathological parameters (stage/grade/metastasis) and poor patient survival. The HAGLR-associated ceRNA network constituted 13 miRNAs and 23 mRNAs differentially expressed in the TCGA-KIRC dataset. From HAGLR recovered mRNA-encoding genes, we developed a 5-gene (PAQR5, ARHGAP24, HABP4, PDLIM5, and RPS6KA2) prognostic signature in the training dataset and validated it in testing as well as entire datasets. The expression level of signature genes showed negative correlation with tumor infiltration of immune cells having adverse impact on ccRCC prognosis and also with tumor derived chemokines facilitating the infiltration. In conclusion, HAGLR seemed to play a tumor suppressive role in ccRCC. HAGLR and associated gene signature may have implementation in improving existing prognostic measure and developing effective immunotherapeutic strategies for ccRCC.

Combinatorial Effects of miRNAs in HSV-2 Infection of Macrophages: An In Silico and In Vitro Integration Approach.

The rising issues of herpes simplex virus (HSV)-2 drug ramifications have encouraged the researchers to look for new and alternative approaches that pose minimum adversities in the host while efficiently reducing the HSV-2 infection. Although microRNAs (miRNAs), as unorthodox approaches, are gaining popularity due to eliciting highly reduced immunogenic reactions, their implications in HSV-2 research have been rarely explored. In this study, a pool of cellular miRNAs with significance in HSV-2-induced inflammatory and immune responses have been identified. Computationally recognizing the host targets of these miRNAs through network biology and machine learning, in vitro validation has been addressed along with the identification of their regulation in the HSV-2 infection. To signify the role of these identified miRNAs, they have been individually ectopically expressed in macrophages. The ectopic expression of the individual miRNAs was able to suppress HSV-2 viral gene expression. Taking a step forward, this study also highlights the Box-Behnken design-based combinatorial effect of ectopically expressed miRNAs on maximum suppression of HSV-2 infectivity. Therefore, the concentrations of each of the miRNAs optimized in a combination, predicted through expert systems biology tools were validated in vitro to not only recover the target expressions but also inhibit the HSV-2 infection in the macrophages. Overall, the study offers miRNAs as intriguing alternatives to commercially available medications against HSV-2. Moreover, the study illuminates the prophylactic potentiality of the miRNAs, which is significant since there are currently no vaccines available for HSV-2. Moving forward, the miRNAs are employed in an innovative strategy that incorporates intricate biological system models and in vitro confirmation methods to deliver a prospective combinatorial miRNA therapeutic against HSV-2 infection.

A computational approach for designing and validating small interfering RNA against SARS-CoV-2 variants.

AIMS: The aim of this study is to develop a novel antiviral strategy capable of efficiently targeting a broad set of SARS-CoV-2 variants. BACKGROUND: Since the first emergence of SARS-CoV-2, it has rapidly transformed into a global pandemic, posing an unprecedented threat to public health. SARS-CoV-2 is prone to mutation and continues to evolve, leading to the emergence of new variants capable of escaping immune protection achieved due to previous SARS-CoV-2 infections or by vaccination. OBJECTIVE: RNA interference (RNAi) is a remarkable biological mechanism that can induce gene silencing by targeting complementary mRNA and inhibiting its translation. METHOD: In this study, using the computational approach, we predicted the most efficient siRNA capable of inhibiting SARS-CoV-2 variants of concern (VoCs). RESULT: The presented siRNA was characterized and evaluated for its thermodynamic properties, offsite-target hits, and in silico validation by molecular docking and molecular dynamics simulations (MD) with Human AGO2 protein. CONCLUSION: The study contributes to the possibility of designing and developing an effective response strategy against existing variants of concerns and preventing further.

Antisense, but not sense, repeat expanded RNAs activate PKR/eIF2α-dependent ISR in C9ORF72 FTD/ALS.

GGGGCC (G4C2) hexanucleotide repeat expansion in the C9ORF72 gene is the most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). The repeat is bidirectionally transcribed and confers gain of toxicity. However, the underlying toxic species is debated, and it is not clear whether antisense CCCCGG (C4G2) repeat expanded RNAs contribute to disease pathogenesis. Our study shows that C9ORF72 antisense C4G2 repeat expanded RNAs trigger the activation of the PKR/eIF2α-dependent integrated stress response independent of dipeptide repeat proteins that are produced through repeat-associated non-AUG-initiated translation, leading to global translation inhibition and stress granule formation. Reducing PKR levels with either siRNA or morpholinos mitigates integrated stress response and toxicity caused by the antisense C4G2 RNAs in cell lines, primary neurons, and zebrafish. Increased phosphorylation of PKR/eIF2α is also observed in the frontal cortex of C9ORF72 FTD/ALS patients. Finally, only antisense C4G2, but not sense G4C2, repeat expanded RNAs robustly activate the PKR/eIF2α pathway and induce aberrant stress granule formation. These results provide a mechanism by which antisense C4G2 repeat expanded RNAs elicit neuronal toxicity in FTD/ALS caused by C9ORF72 repeat expansions.

miRNAs in Herpesvirus Infection: Powerful Regulators in Small Packages.

microRNAs are a class of small, single-stranded, noncoding RNAs that regulate gene expression. They can be significantly dysregulated upon exposure to any infection, serving as important biomarkers and therapeutic targets. Numerous human DNA viruses, along with several herpesviruses, have been found to encode and express functional viral microRNAs known as vmiRNAs, which can play a vital role in host-pathogen interactions by controlling the viral life cycle and altering host biological pathways. Viruses have also adopted a variety of strategies to prevent being targeted by cellular miRNAs. Cellular miRNAs can act as anti- or proviral components, and their dysregulation occurs during a wide range of infections, including herpesvirus infection. This demonstrates the significance of miRNAs in host herpesvirus infection. The current state of knowledge regarding microRNAs and their role in the different stages of herpes virus infection are discussed in this review. It also delineates the therapeutic and biomarker potential of these microRNAs in future research directions.

Comprehensive data and workflow for mapping global proteome and post-translational modifications in Indian Major Carp, Labeo rohita.

We present the data for the global proteome and post-translational modification mapping of Labeo rohita (Rohu) which consists of mass-spectrometric (MS) data for 8498 proteins at 1% false discovery rate, which constitutes 26% of the total protein-coding sequences in Rohu. This data consists of deep proteomics of 17 normal tissues including eye, spinal cord, brain, male gonad, female gonad, gill, air bladder, gall bladder, gut, liver, heart, kidney, skin, scales, muscle, fin, spleen, as well as blood plasma and embryo of Rohu. The data from SRM-based targeted analysis to validate the presence of few key proteins is also included. Global post translational modification-based analysis (global PTM) was also performed in the studied tissues and its background data is also publicly accessible. This data and the web-based proteome map may aid applied and basic research endeavors in aquaculture to meet the food demands and nutritional security challenges of an increasing world population. The data here is related to the research article "Organ-based proteome and post-translational modification profiling of a widely cultivated tropical water fish, Labeo rohita" in the Journal of Proteome Research [1].

Altered Behavioral Responses Show GABA Sensitivity in Muscleblind-Like 2-Deficient Mice: Implications for CNS Symptoms in Myotonic Dystrophy.

Considerable evidence from mouse models and human postmortem brain suggests loss of Muscleblind-like protein 2 (MBNL2) function in brain is a major driver of CNS symptoms in Myotonic dystrophy type 1 (DM1). Increased hypersomnia, fatigue, and surgical complications associated with general anesthesia suggest possible sensitivity to GABAergic inhibition in DM1. To test the hypothesis that MBNL2 depletion leads to behavioral sensitivity to GABAA receptor (GABAA-R) modulation, Mbnl2 knock-out (KO) and wild-type (WT) littermates were treated with the anesthetic sevoflurane, the benzodiazepine diazepam, the imidazopyridine zolpidem, and the benzodiazepine rescue agent, flumazenil (Ro 15-1788), and assessed for various behavioral metrics. Mbnl2 KO mice exhibited delayed recovery following sevoflurane, delayed emergence and recovery from zolpidem, and enhanced sleep time at baseline that was modulated by flumazenil. A significantly higher proportion of Mbnl2 KO mice also loss their righting reflex [loss of righting reflex (LORR)] from a standard diazepam dose. We further examined whether MBNL2 depletion affects total GABAA-R mRNA subunit levels and validated RNA-sequencing data of mis-spliced Gabrg2, whose isoform ratios are known to regulate GABA sensitivity and associated behaviors. While no other GABAA-R subunit mRNA levels tested were altered in Mbnl2 KO mouse prefrontal cortex, Gabrg2S/L mRNA ratio levels were significantly altered. Taken together, our findings indicate that loss of MBNL2 function affects GABAergic function in a mouse model of myotonic dystrophy (DM1).

Differential Microbial Signature Associated With Benign Prostatic Hyperplasia and Prostate Cancer.

Apart from other risk factors, chronic inflammation is also associated with the onset of Prostate Cancer (PCa), wherein pathogen infection and tissue microbiome dysbiosis are known to play a major role in both inflammatory response and cancer development. However, except for a few studies, the link between microbes and PCa remained poorly understood. To explore the potential microbiome signature associated with PCa in Indian patients, we investigated differential compositions of commensal bacteria among patients with benign prostatic hyperplasia (BPH) and PCa using 16S rRNA amplicon sequencing followed by qPCR analyses using two distinct primer sets. Using two independent cohorts, we show that Prevotella copri, Cupriavidus campinensis, and Propionibacterium acnes represent the three most abundant bacteria in diseased prostate lesions. LEfSe analyses identified that while Cupriavidus taiwanensis and Methylobacterium organophilum are distinctly elevated in PCa samples, Kocuria palustris and Cellvibrio mixtus are significantly enriched in BPH samples. Furthermore, we identify that a number of human tumor viruses, including Epstein-Barr virus (EBV) and hepatitis B virus (HBV), along with two high-risk human papillomaviruses - HPV-16 and HPV-18, are significantly associated with the PCa development and strongly correlated with PCa bacterial signature. The study may thus offer to develop a framework for exploiting this microbial signature for early diagnosis and prognosis of PCa development.

Genotypic Characterization of Orientia tsutsugamushi Isolated From Acute Encephalitis Syndrome and Acute Febrile Illness Cases in the Gorakhpur Area, Uttar Pradesh, India.

Scrub typhus infections caused by Orientiatsutsugamushi (OT), continue to remain underdiagnosed globally, due to the lack of distinctive symptoms. The elusive nature of the Acute Encephalitis Syndrome (AES) outbreak in Gorakhpur, Uttar Pradesh that claimed numerous pediatric lives was the driving force of this study which involved serological diagnosis (IgM-ELISA), isolation of OT in cell culture, confirmation by PCR, and characterization by Sanger sequencing. In total, 12 out of 36 patients were seropositive, of which 4 were positive by PCR. Upon enrichment in cell culture, additional 3 patients (including two seronegative) were detected positive by PCR. In total, three of these 7 patients were found to be infected with two strains of OT. Taken together, this study for the first time reports the occurrence of dual infections in addition to three circulating OT genotypes (Gilliam, Kato, and Karp-like) and highlights the significance of enriching OT in cell culture systems for efficient molecular detection.

A tale of antiviral counterattacks in rotavirus infection.

Human rotaviruses are the utmost etiologic agents of infantile gastroenteritis in children under five years of age. To reduce childhood morbidity and mortality caused by this rotavirus infection, numerous efforts are being made worldwide in the form of better and universal immunisation programmes. Though few vaccines are in action, the lack of approved antiviral agents that have potential combative effects against the rotavirus infection in the host, remains a point of concern. This review focuses on recent insights into the development of naturally derived, RNA-silencing-based drug substances that show their anti-rotaviral activities by targeting and influencing different host and/or viral factors that contribute directly or indirectly to successful viral pathogenesis.

Rotavirus-Mediated Suppression of miRNA-192 Family and miRNA-181a Activates Wnt/ß-Catenin Signaling Pathway: An In Vitro Study.

The significance of the Wnt/ß-catenin signaling cascade in Rotavirus (RV) infection has not been elucidated. In this study, we attempt to elucidate the importance of the Wnt/ß-catenin pathway in the RV pathogenesis and investigate a miRNA-mediated approach to regulate the pathway to repress the RV infection in the host. The regulation of the Wnt signaling pathway in terms of ß-catenin accumulation and activation was analyzed by Western blotting and Confocal imaging analysis. The expression levels of miR-192 family members and miR-181a were enquired into using qPCR assays, whereas their targets in the Wnt pathway were confirmed using the Luciferase Reporter Assays. Members of the miR-192 family and miR-181a, which target the components of the pathway, were also found to be considerably decreased in expression during RV infection. Ectopic expression of these miRNAs could restrict the RV pathogenesis by targeting the intermediates of the Wnt signaling pathway. The miR-192 family and miR-181a were capable of suppressing the RV infection via targeting of the Wnt/ß-catenin pathway. The study not only highlights the role of the Wnt signaling cascade in RV infection but also suggests that miRNAs can synergistically decrease RV replication by a significant amount. Thus, the miR-192 family and miR-181a present themselves as prospective antivirals against RV infection.

PRNCR1: a long non-coding RNA with a pivotal oncogenic role in cancer.

Long non-coding RNAs (lncRNAs) have been gaining importance in the field of cancer research in recent years. PRNCR1 (prostate cancer-associated non-coding RNA1) is a 12.7 kb, intron-less lncRNA found to play an oncogenic role in malignancy of diverse organs including prostate, breast, lung, oral cavity, colon and rectum. Single-nucleotide polymorphisms (SNPs) of PRNCR1 locus have been found to be associated with cancer susceptibility in different populations. In this review, an attempt has been made for the first time to summarize all sorts of available data on PRNCR1 to date from relevant databases (GeneCard, LncExpDB, Ensembl genome browser, and PubMed). As functional roles of PRNCR1, miRNA (microRNA) sponging was mostly highlighted in the pathogenesis of different cancer; in addition, an association of the lncRNA with chromatin-modifying complex to enhance androgen receptor-mediated gene transcription was reported in prostate cancer. Diagnostic and prognostic importance of PRNCR1 was found in some malignancies suggesting potency of the lncRNA to serve as a clinical biomarker. For PRNCR1 SNPs, although cancer susceptibility of the risk alleles/genotypes was reported in different populations, majorities of the findings were not replicated and underlying molecular mechanisms remained unexplored. Therapeutic implication of PRNCR1 was not studied well and future research may come up in this direction for intervening novel strategies to fight against cancer.