Multiple sexually transmitted infections as a presenting feature of human immunodeficiency virus/AIDS.

A 45-year-old married male presented with nonhealing, painless ulcers with purulent discharge over genitals for 3 months. He had molluscum contagiosum over genitalia and forehead. A tissue smear suggested a diagnosis of donovanosis. Biopsy suggested diagnosis of molluscum contagiosum and serology was positive for human immunodeficiency virus 1 and herpes simplex 2. The patient was started on acyclovir and doxycycline. Antiretroviral therapy was initiated. The patient responded slowly over a period of 8 weeks. Immunocompromised patients having nonhealing genital ulcers must be subjected to tissue smear to pick up the diagnosis of granuloma inguinale.

Biocatalytic Nucleobase Diversification of 4'-Thionucleosides and Application of Derived 5-Ethynyl-4'-thiouridine for RNA Synthesis Detection.

Nucleoside and nucleotide analogues have proven to be transformative in the treatment of viral infections and cancer. One branch of structural modification to deliver new nucleoside analogue classes explores replacement of canonical ribose oxygen with a sulfur atom. Whilst biological activity of such analogues has been shown in some cases, widespread exploration of this compound class is hitherto hampered by the lack of a straightforward and universal nucleobase diversification strategy. Herein, we present a synergistic platform enabling both biocatalytic nucleobase diversification from 4'-thiouridine in a one-pot process, and chemical functionalization to access new entities. This methodology delivers entry across pyrimidine and purine 4'-thionucleosides, paving a way for wider synthetic and biological exploration. We exemplify our approach by enzymatic synthesis of 5-iodo-4'-thiouridine on multi-milligram scale and from here switch to complete chemical synthesis of a novel nucleoside analogue probe, 5-ethynyl-4'-thiouridine. Finally, we demonstrate the utility of this probe to monitor RNA synthesis in proliferating HeLa cells, validating its capability as a new metabolic RNA labelling tool.

Uncovering the secret weapons of an invasive plant: The endophytic microbes of Anthemis cotula.

Understanding plant-microbe interaction can be useful in identifying the microbial drivers of plant invasions. It is in this context that we explored the diversity of endophytic microbes from leaves of Anthemis cotula, an annual plant that is highly invasive in Kashmir Himalaya. We also tried to establish the role of endophytes in the invasiveness of this alien species. We collected and processed leaf samples from three populations at three different sites. A total of 902 endophytic isolates belonging to 4 bacterial and 2 fungal phyla were recovered that belonged to 27 bacterial and 14 fungal genera. Firmicutes (29.1%), Proteobacteria (24.1%), Ascomycota (22.8%) and Actinobacteria (19%) were dominant across all samples. Plant growth promoting traits, such as Ammonia production, Indole Acetic Acid (IAA) production, Phosphate solubilization and biocontrol activity of these endophytes were also studied and most of the isolates (74.68%) were positive for ammonia production. IAA production, phosphate solubilization and biocontrol activity was present in 39.24%, 36.70% and 20.26% isolates, respectively. Furthermore, Botrytis cinerea, a pathogen of A. cotula in its native range, though present in Kashmir Himalaya does not affect A. cotula probably due to the presence of leaf endophytic microbial antagonists. Our results highlight that the beneficial plant growth promoting interactions and enemy suppression by leaf endophytes of A. cotula, may be contributing to its survival and invasion in the Kashmir Himalaya.

Cost analysis of different medical oxygen sources for a healthcare facility in India.

Background and Aims: Multiple sources of medical oxygen, namely liquid medical oxygen (LMO) tanks, pressure swing adsorption (PSA) plants, concentrators, and gaseous cylinders, are available at different healthcare facilities. These sources of oxygen have varying installation and operational costs. In low-resource settings, it is imperative to utilise these assets optimally. This study investigated the operational costs of multiple oxygen sources available at a healthcare facility. Methods: A Microsoft (MS) Excel-based model was developed to analyse and compare the oxygen manufacturing costs (in ₹/m3) using PSA plants and procurement costs (in ₹/m3) of LMO and third-party vendor-refilled cylinders. Results: The oxygen manufacturing costs for PSA plants of different capacities and running times on electricity and diesel generators (DGs) as a power source were calculated. This study highlights the cost-benefit of using PSA plants over LMO and third-party vendor-refilled cylinders as a source of oxygen. PSA plants are most economical when they are of higher capacity and used to their maximum capacity on electricity as the power source. On the contrary, they are most expensive when used on a DG set as a power source. Furthermore, this study provides evidence of PSA plants being more cost-effective for refilling cylinders using a booster compressor unit when compared to third-party vendor-cylinder refilling. Conclusion: Given their cost-effectiveness and low third-party dependence, they should be utilised to their maximum capacity as medical oxygen sources at healthcare facilities.

Ambient Temperature Metal-Free Thiomethylation of Chloroheteroarenes and Chloropurines.

Herein, we report an in-situ mild and metal-free protocol for thiomethylation of heteroarenes in high yields. The thiomethylation of various chloropurines, nucleosides, and chloroheteroarenes has been accomplished offering easy access to agrochemicals and synthetic molecules useful for drug discovery.

Assessing the Impact of Precancerous Lesions on Oral Health-Related Quality of Life: A Study at Tertiary Care Hospital.

Objective: The aim of this cross-sectional study was to assess the oral health-related quality of life (OHRQoL) in a cohort of 500 patients diagnosed with precancerous lesions and conditions at a tertiary care hospital in Central India. Methods: 500 patients with confirmed precancerous oral lesions and conditions were recruited for the study. The Oral Health Impact Profile (OHIP-14) questionnaire, a validated instrument consisting of 14 items, was used to assess the OHRQoL of the participants. The OHIP-14 questionnaire scores were statistically analyzed using appropriate methods. Results: The majority of the participants were with a mean age of 48 years. The mean OHIP-14 score was calculated to be 45.1, indicating the overall impact of oral health on the quality of life of patients with precancerous lesions and conditions. The individual domains most affected were functional limitations and physical pain. Conclusion: This study demonstrates that promoting oral health awareness and regular screenings in the community is needed to prevent the progression of oral precancerous conditions and ultimately reduce the burden of oral cancer.

Difluoroacetic acid: an alternative acid in the detritylation reaction for the solid-phase synthesis of oligonucleotides.

Dichloroacetic acid or trichloroacetic acid are commonly used in the detritylation reaction of the automated solid-phase synthesis of oligonucleotides. Dichloroacetic acid, however, is often contaminated with trichloroacetaldehyde (chloral), leading to the formation of inseparable impurities in the final oligonucleotide product. In this work, three different sequences, namely T18, d(TAA)6, and an 18-mer mixed sequence, were used as models to compare the deprotection efficiency of three acids: trichloroacetic acid, dichloroacetic acid, and difluoroacetic acid. Comparable purities of full-length products were obtained for the synthesis of the three model sequences when dichloroacetic acid or difluoroacetic acid were used during the detritylation reaction, however, conditions need to be optimized for the synthesis of purine-rich sequences. Therefore, difluoroacetic acid is a potential alternative to dichloroacetic acid in the solid-phase synthesis of oligonucleotides to avoid the impurity formation due to presence of chloral.

An Update on Protection of 5'-Hydroxyl Functions of Nucleosides and Oligonucleotides.

The synthesis of natural and chemically modified nucleosides and oligonucleotides is in great demand due to its increasing number of applications in diverse areas of research. These include tools for diagnostics and proteomics, research reagents for molecular biology, probes for functional genomics, and the design, discovery, development, and manufacture of new therapeutics. The likelihood of success in synthesizing these molecules is often dependent on the correct choice of a protection strategy to block the 5'-hydroxyl group of a carbohydrate moiety, nucleoside, or oligonucleotide. This topic was reviewed extensively in the year 2000. The purpose of this article is to complement and update the original review with recently published methodologies recommended for the protection and deprotection of the 5'-hydroxyl group. © 2024 Wiley Periodicals LLC.

Design, synthesis, and molecular modeling studies of novel 2-quinolone-1,2,3-triazole-α-aminophosphonates hybrids as dual antiviral and antibacterial agents.

With the aim to identify new antiviral agents with antibacterial properties, a series of 2-quinolone-1,2,3-triazole derivatives bearing α-aminophosphonates was synthesized and characterized by 1H NMR, 13C NMR, 31P NMR, single crystal XRD and HRMS analyses. These compounds were examined against five RNA viruses (YFV, ZIKV, CHIKV, EV71 and HRV) from three distinct families (Picornaviridae, Togaviridae and Flaviviridae) and four bacterial strains (S. aureus, E. feacalis, E. coli and P. aeruginosa). The α-aminophosphonates 4f, 4i, 4j, 4k, 4p and 4q recorded low IC50 values of 6.8-10.91 µM, along with elevated selectivity indices ranging from 2 to more than 3, particularly against YFV, CHIKV and HRV-B14. Besides, the synthesized compounds were generally more sensitive toward Gram-positive bacteria, with the majority of them displaying significant potency against E. feacalis. Specifically, an excellent anti-enterococcus activity was obtained by compound 4q with MIC and MBC values of 0.03 µmol/mL, which were 8.7 and 10 times greater than those of the reference drugs ampicillin and rifampicin, respectively. Also, compounds 4f, 4p and 4q showed potent anti-staphylococcal activity with MIC values varying between 0.11 and 0.13 µmol/mL, compared to 0.27 µmol/mL for ampicillin. The results from DFT and molecular docking simulations were in agreement with the biological assays, proving the binding capability of hybrids 4f, 4i, 4j, 4k, 4p and 4q with viral and bacterial target enzymes through hydrogen bonds and other non-covalent interactions. The in silico ADME/Tox prediction revealed that these molecules possess moderate to good drug-likeness and pharmacokinetic properties, with a minimal chance of causing liver toxicity or carcinogenic effects.

Resolving the topology of encircling multiple exceptional points.

Non-Hermiticity has emerged as a new paradigm for controlling coupled-mode systems in ways that cannot be achieved with conventional techniques. One aspect of this control that has received considerable attention recently is the encircling of exceptional points (EPs). To date, most work has focused on systems consisting of two modes that are tuned by two control parameters and have isolated EPs. While these systems exhibit exotic features related to EP encircling, it has been shown that richer behavior occurs in systems with more than two modes. Such systems can be tuned by more than two control parameters, and contain EPs that form a knot-like structure. Control loops that encircle this structure cause the system's eigenvalues to trace out non-commutative braids. Here we consider a hybrid scenario: a three-mode system with just two control parameters. We describe the relationship between control loops and their topology in the full and two-dimensional parameter space. We demonstrate this relationship experimentally using a three-mode mechanical system in which the control parameters are provided by optomechanical interaction with a high-finesse optical cavity.

Cytomorphometric analysis of buccal mucosal cells in iron deficiency anemia: A cross-sectional study.

Background: Worldwide, at any given moment, more individuals have iron deficiency anemia (IDA) than any other health problems. Very few studies have been conducted to evaluate changes in oral mucosa in IDA. The present study is undertaken for cytomorphometric analysis of buccal mucosal cells in IDA. Nuclear diameter (ND), cell diameter (CD), nuclear area (NA), cell area (CA), and nuclear-cytoplasmic ratio (N/C) are measured and compared in buccal mucosal cells of IDA patients and controls. Aims: To evaluate cytomorphometric changes in epithelial cells of oral mucosa in IDA and to compare these changes with the controls. Settings and Design: A cross-sectional study. Methods and Materials: Forty cases of IDA and forty cases of control group were selected for the study. IDA cases were diagnosed with decreased Hb level, MCV, MCH, MCHC and confirmed by decreased serum iron and increased total iron-binding capacity levels. Cytomorphometric analysis of buccal mucosa was performed to study CA, CD, NA, ND, and N/C ratio. Statistical Analysis Used: Statistical analysis was done using t- test in SPSS software version 4. Result: Results of our study showed increased cell area, cell diameter, nuclear area, nuclear diameter, and nuclear-cytoplasmic ratio in anemic group as compared to controls. Conclusion: The study suggests that individuals with IDA regardless of clinically visible oral lesions show cytological changes in oral mucosal epithelium. Knowledge of quantitative alterations in oral epithelial cells of IDA patients is important as these alterations are similar to those seen in precancerous and radiation-induced changes. Cytomorphometry is an efficient tool to understand the extent of cellular changes that occur in oral epithelial cells in IDA.

Functional antagonism and insights into the biosynthetic potential of human gut-derived microbes.

The specialised small molecules encoded by commensal microbes mediate distinct functional interactions. However, there is a landscape of antagonistic interactions mediated by specialised strains and their small molecules. Herein, the antagonistic landscape within a collection of 330 human gut-derived commensal microbial strains was elucidated to evaluate antimicrobial interactions as a defensive contributor, and gain new insights into structure-related functions. The potential antagonistic gut-derived strains displayed strain-specific selective inhibition. This is in contrast to common antimicrobial drugs, which typically wipe out a broad range of species and are usually found in environmental microbes. Genome sequencing of representative gut strains revealed the presence of significant biosynthetic gene clusters (BGCs) encoding compound families that contribute to antagonistic activities, and are important in host defence and maintaining gut homeostasis. Subsets of these BGCs were abundant in metagenomic sequencing data from healthy individuals. Furthermore, the cell culture secretome of these strains revealed potential biomarkers linked to hallmark pathways. These microorganisms have biosynthetic novelty and are a source of biologically significant natural products. Such natural products are essential in the development of new antimicrobial agents to reduce the usage of broad-spectrum antibiotics and combat antimicrobial resistance.

Organic-inorganic hybrid material for hole transport in inverted perovskite solar cells.

Hole mobility is critical to the power conversion efficiencies of perovskite solar cells (PSCs). Organic small-molecule hole-transporting materials (HTMs) have attracted considerable interest in PSCs due to their structural flexibility and operational durability, but they suffer from modest hole mobility. On the other hand, inorganic HTMs with good hole mobility are inflexible in structural variation and exhibit unsatisfactory cell efficiency. In this study, a ligand BT28 and its zinc-based coordination complex BTZ30 were synthesized, characterized, and investigated as HTMs for PSC applications. The mixed-halide perovskites can be grown uniformly with large crystalline grains on both HTMs, which exhibit similar optical and electrochemical properties. However, it was discovered that the BTZ30-based solar cell exhibited an open-circuit voltage of 1.0817 V and a high short-circuit current density of 23.1392 mA cm-2 with a champion power conversion efficiency of close to 20 %. The performance difference between the two HTMs can be attributed to the difference in their hole mobilities, which is 63.31 % higher for BTZ30 than BT28. The comparison of non-metal and metal HTMs revealed the importance of considering hybrid structures to overcome some shortcomings associated with organic and inorganic HTMs and achieve high-performance PSCs.

Community characterization of soil from the Central Deccan Plateau dry tropical deciduous forest (Ceddtrof) in central India using 16S rRNA gene amplicon sequencing.

We report a preliminary study of soil from the Central Deccan Plateau dry tropical deciduous forest in India using 16S rRNA gene amplicon sequencing. We report diverse taxa, e.g., Proteobacteria, Actinobacteria, Acidobacteria, Plactomycetes, Chloroflexi, Bacteroidetes, Verrucomicrobia, Gemmatimonadetes, Firmicutes, Crenarchaeota, Nitrospirae, Armatimonadetes, Elusimicrobia, Cyanobacteria, Chlamydiae, Chlorobi, Parvachaeota, Tenericutes, Euryarchaeota, Fibrobacteres, Calditrix, and Spirochaetes.

Investigation of new 1,2,3-triazolyl-quinolinyl-propan-2-ol derivatives as potential antimicrobial agents: in vitro and in silico approach.

A new series of 1-((1-(4-substituted benzyl)-1H-1,2,3-triazol-4-yl)methoxy)-2-(2-substituted quinolin-4-yl)propan-2-ol (9a-x) have been synthesized. The newly synthesized 1,2,3-triazolyl-quinolinyl-propan-2-ol (9a-x) derivatives were screened for in vitro antimicrobial activity against M. tuberculosis H37Rv, E. coli, P. mirabilis, B. subtilis, and S. albus. Most of the compounds showed good to moderate antibacterial activity and all derivatives have shown excellent to good antitubercular activity with MIC 0.8-12.5 µg/mL. To know the plausible mode of action for antibacterial activity the docking study against DNA gyrase from M. tuberculosis and S. aureus was investigated. The compounds have shown significant docking scores in the range of -9.532 to -7.087 and -9.543 to -6.621 Kcal/mol with the DNA gyrase enzyme of S. aureus (PDB ID: 2XCT) and M. tuberculosis (PDB ID: 5BS8), respectively. Against the S. aureus and M. tuberculosis H37Rv strains, the compound 9 l showed good activity with MIC values of 62.5 and 3.33 µM. It also showed significant docking scores in both targets with -8.291 and -8.885 Kcal/mol, respectively. Molecular dynamics was studied to investigate the structural and dynamics transitions at the atomistic level in S. aureus DNA gyrase (2XCT) and M. tuberculosis DNA gyrase (5BS8). The results revealed that the residues in the active binding pockets of the S. aureus and M. tuberculosis DNA gyrase proteins that interacted with compound 9 l remained relatively consistent throughout the MD simulations and thus, reflected the conformation stability of the respective complexes. Thus, the significant antimicrobial activity of derivatives 9a-x recommended that these compounds could assist in the development of lead compounds to treat for bacterial infections.Communicated by Ramaswamy H. Sarma.

Synthesis of 2'-O-Methyl/2'-O-MOE-L-Nucleoside Derivatives and Their Applications: Preparation of G-Quadruplexes, Their Characterization, and Stability Studies.

Nucleosides and their analogues constitute an important family of molecules with potential antiviral and antiproliferative activity. The enantiomers of natural nucleosides, l-nucleoside derivatives, which have comparable biological activity but more favorable toxicological properties and greater metabolic stability than d-nucleosides, have emerged as a new class of therapeutic agents. Furthermore, l-nucleosides can be used as a building block to prepare l-oligonucleotides, which have identical physical properties in terms of solubility, hybridization kinetics, and duplex thermal stability as d-oligonucleotides but completely orthogonal in nature. Consequently, they are resistant to nuclease degradation, nontoxic, and immunologically passive, which are desirable properties for biomedical applications. Herein, we describe the synthesis of several 2'-O-methyl/2'-O-MOE-l-nucleoside pyrimidine derivatives and their incorporation into G-rich oligonucleotides. Finally, we evaluated the stability and resistance against nucleases of these new G-quadruplexes, demonstrating the potential of the l-nucleosides described in this work in providing enhanced nuclease resistance with a minimal impact in the nucleic acid structural properties.

Synthesis and Structural Studies of Nucleobase Functionalized Hydrogels for Controlled Release of Vitamins.

The development of biomolecule-derived biocompatible scaffolds for drug delivery applications is an emerging research area. Herein, we have synthesized a series of nucleobase guanine (G) functionalized amino acid conjugates having different chain lengths to study their molecular self-assembly in the hydrogel state. The gelation properties have been induced by the correct choice of chain lengths of fatty acids present in nucleobase functionalized molecules. The effect of alkali metal cations, pH, and the concentration of nucleobase functionalized amino acid conjugates in the molecular self-assembly process has been explored. The presence of Hoogsteen hydrogen bonding interaction drives the formation of a G-quadruplex functionalized hydrogel. The DOSY nuclear magnetic resonance is also performed to evaluate the self-assembling behavior of the newly formed nucleobase functionalized hydrogel. The nanofibrillar morphology is responsible for the formation of a hydrogel, which has been confirmed by various microscopic experiments. The mechanical behaviors of the hydrogel were evaluated by rheological experiments. The in vitro biostability of the synthesized nucleobase amino acid conjugate is also investigated in the presence of hydrolytic enzymes proteinase K and chymotrypsin. Finally, the nucleobase functionalized hydrogel has been used as a drug delivery platform for the control and sustained pH-responsive release of vitamins B2 and B12. This synthesized nucleobase functionalized hydrogel also exhibits noncytotoxic behavior, which has been evaluated by their in vitro cell viability experiment using HEK 293 and MCF-7 cell lines.

Investigation of tRNA-based relatedness within the Planctomycetes-Verrucomicrobia-Chlamydiae (PVC) superphylum: a comparative analysis.

The PVC superphylum is a diverse group of prokaryotes that require stringent growth conditions. RNA is a fascinating molecule to find evolutionary relatedness according to the RNA World Hypothesis. We conducted tRNA gene analysis to find evolutionary relationships in the PVC phyla. The analysis of genomic data (P = 9, V = 4, C = 8) revealed that the number of tRNA genes varied from 28 to 90 in Planctomycetes and Chlamydia, respectively. Verrucomicrobia has whole genomes and the longest scaffold (3 + 1), with tRNA genes ranging from 49 to 53 in whole genomes and 4 in the longest scaffold. Most tRNAs in the E. coli genome clustered with homologs, but approximately 43% clustered with tRNAs encoding different amino acids. Planctomyces, Akkermansia, Isosphaera, and Chlamydia were similar to E. coli tRNAs. In a phylum, tRNAs coding for different amino acids clustered at a range of 8 to 10%. Further analysis of these tRNAs showed sequence similarity with Cyanobacteria, Proteobacteria, Viridiplantae, Ascomycota and Basidiomycota (Eukaryota). This indicates the possibility of horizontal gene transfer or, otherwise, a different origin of tRNA in PVC bacteria. Hence, this work proves its importance for determining evolutionary relatedness and potentially identifying bacteria using tRNA. Thus, the analysis of these tRNAs indicates that primitive RNA may have served as the genetic material of LUCA before being replaced by DNA. A quantitative analysis is required to test these possibilities that relate the evolutionary significance of tRNA to the origin of life.

A practical and scalable synthesis of several base modified 3'-O-methyl ribonucleosides.

An easy and efficient large-scale synthesis of 1, 2,-di-O-acetyl-5-O-benzoyl-3-O-methyl-d-ribofuranose (8) was accomplished from commercial 1,2:5,6-di-O-isopropylidene-α-d-allofuranose in 7-steps and 30 % overall yield. The utility of protected 8 was demonstrated via synthesis of 9-(3'-O-methyl-ß-d-ribofuranosyl)-6-chloropurine (21) and six other nucleoside analogues in good yields. A library of five novel base modified nucleosides were generated starting from purine nucleoside 21 via functional group manipulations. The 3'-O-modified nucleosides are known to act as chain terminator exerting antiviral activity. The synthesis strategy described herein offers direct access to 3'-O-alkylated nucleosides with wide range of applications, including cap analogues for mRNA vaccine production. This protocol provides a route to exclusive synthesis of 3'-O-alkylated nucleosides, devoid of isomeric 2'-O-alkylated products essential for both therapeutic and biological research.

Effect of long-term oral glutathione supplementation on gut microbiome of type 2 diabetic individuals.

The aim of this study was to check the effect of long-term oral glutathione (GSH) supplementation on alteration in gut microbiome of Indian diabetic individuals. Early morning fresh stool sample of diabetic individuals recruited in a randomized clinical trial wherein they were given 500 mg GSH supplementation orally once a day for a period of 6 months was collected and gut microbiome was analysed using high throughput 16S rRNA metagenomic sequencing. Long-term GSH supplementation as reported in our earlier work showed significant increase in body stores of GSH and stabilized decreased glycated haemoglobin (HbA1c). Analysis of gut microbiome revealed that abundance of phylum Proteobacteria significantly decreased (P < 0.05) in individuals with GSH supplementation after 6 months compared to those without it. Beneficial dominant genera such as Megasphaera, Bacteroides, and Megamonas were found to be significantly enriched (P < 0.05), while pathogenic Escherichia/Shigella was found to be depleted (P < 0.05) after supplementation. Data clearly demonstrate that GSH supplementation along with antidiabetic treatment helps restore the gut microbiome by enriching beneficial bacteria of healthy gut and reducing significantly the load of pathogenic bacteria of diabetic gut.