Development of a Spectral Library for the Discovery of Altered Genomic Events in Mycobacterium avium Associated With Virulence Using Mass Spectrometry-Based Proteogenomic Analysis.

Mycobacterium avium is one of the prominent disease-causing bacteria in humans. It causes lymphadenitis, chronic and extrapulmonary, and disseminated infections in adults, children, and immunocompromised patients. M. avium has ∼4500 predicted protein-coding regions on average, which can help discover several variants at the proteome level. Many of them are potentially associated with virulence; thus, identifying such proteins can be a helpful feature in developing panel-based theranostics. In line with such a long-term goal, we carried out an in-depth proteomic analysis of M. avium with both data-dependent and data-independent acquisition methods. Further, a set of proteogenomic investigations were carried out using (i) a protein database for Mycobacterium tuberculosis, (ii) an M. avium genome six-frame-translated database, and (iii) a variant protein database of M. avium. A search of mass spectrometry data against M. avium protein database resulted in identifying 2954 proteins. Further, proteogenomic analyses aided in identifying 1301 novel peptide sequences and correcting translation start sites for 15 proteins. Ultimately, we created a spectral library of M. avium proteins, including novel genome search-specific peptides and variant peptides detected in this study. We validated the spectral library by a data-independent acquisition of the M. avium proteome. Thus, we present an M. avium spectral library of 29,033 peptide precursors supported by 0.4 million fragment ions for further use by the biomedical community.

Design principles and functional basis of enantioselectivity of alanyl-tRNA synthetase and a chiral proofreader during protein biosynthesis.

Homochirality of the cellular proteome is attributed to the L-chiral bias of the translation apparatus. The chiral specificity of enzymes was elegantly explained using the 'four-location' model by Koshland two decades ago. In accordance with the model, it was envisaged and noted that some aminoacyl-tRNA synthetases (aaRS) that charge larger amino acids are porous to D-amino acids. However, a recent study showed that alanyl-tRNA synthetase (AlaRS) can mischarge D-alanine and that its editing domain, but not the universally present D-aminoacyl-tRNA deacylase (DTD), is responsible for correcting the chirality-based error. Here, using in vitro and in vivo data coupled with structural analysis, we show that AlaRS catalytic site is a strict D-chiral rejection system and therefore does not activate D-alanine. It obviates the need for AlaRS editing domain to be active against D-Ala-tRNAAla and we show that it is indeed the case as it only corrects L-serine and glycine mischarging. We further provide direct biochemical evidence showing activity of DTD on smaller D-aa-tRNAs that corroborates with the L-chiral rejection mode of action proposed earlier. Overall, while removing anomalies in the fundamental recognition mechanisms, the current study further substantiates how chiral fidelity is perpetuated during protein biosynthesis.

Electrostatics Choreographs the Aggregation Dynamics of Full-Length TDP-43 via a Monomeric Amyloid Precursor.

TDP-43 is a ubiquitously expressed, multidomain functional protein that is distinctively known to form aggregates in many fatal neurodegenerative disorders. However, the information for arresting TDP-43 aggregation is missing due to a lack of understanding of the molecular mechanism of the aggregation and structural properties of TDP-43. TDP-43 is inherently prone to aggregation and has minimal protein solubility. Multiple studies have been performed on the smaller parts of TDP-43 or the full-length protein attached to a large solubilization tag. However, the presence of co-solutes or solubilization tags is observed to interfere with the molecular properties and aggregation mechanism of full-length TDP-43. Notably, this study populated and characterized the native, dimeric state of TDP-43 without the interference of co-solutes or protein modifications. We observed that the electrostatics of the local environment is capable of the partial unfolding and monomerization of the native dimeric state of TDP-43 into an amyloidogenic molten globule. By employing the tools of thermodynamics and kinetics, we reveal the structural characteristics and temporal order of the early intermediates and transition states during the transition of the molten globule to ß-rich, amyloid-like aggregates of TDP-43, which is governed by the electrostatics of the environment. The current advanced understanding of the nature of native and early aggregation-prone intermediates, early steps, and the influence of electrostatics in TDP-43 aggregation is essential for drug design.

Comprehensive analytics for virus-cell and cell-cell multinucleation system.

Cell-fusion mediated generation of multinucleated syncytia represent critical feature during viral infection and in development. Efficiency of syncytia formation is usually illustrated as fusion efficiency under given condition by quantifying total number of nuclei in syncytia normalized to total number of nuclei (both within syncytia and unfused cell nuclei) in unit field of view. However heterogeneity in multinucleated syncytia sizes poses challenge in quantification of cell-fusion multinucleation under diverse conditions. Taking in-vitro SARS-CoV-2 spike-protein variants mediated virus-cell fusion model and placenta trophoblast syncytialization as cell-cell fusion model; herein we emphasize wide application of simple unbiased detailed measure of virus-cell and cell-cell multinucleation using experiential cumulative distribution function (CDF) and fusion number events (FNE) approaches illustrating comprehensive metrics for syncytia interpretation.

A Single Enzyme in Enantiocomplementary Synthesis of ß-Nitroalcohols: Bidirectional Catalysis by Hydroxynitrile Lyase.

A single enzyme, Baliospermum montanum hydroxynitrile lyase (BmHNL), without alteration, enabled bidirectional catalysis in enantiocomplementary synthesis of chiral ß-nitroalcohols. BmHNL catalyzed promiscuous Henry (24 examples) and retro-Henry reaction (22 examples) provided up to >99% and 50% conversion to (S)- and (R)-ß-nitroalcohols respectively, while both cases displayed up to >99% ee. The broad substrate scope and high stereoselectivity of BmHNL represents its synthetic applications in sustainable production of diverse chiral ß-nitroalcohols. Kinetic parameters of BmHNL was determined for Henry and retro-Henry reaction, which reveals poor catalytic efficiency for both the promiscuous transformations, however, the former has better efficiency than the latter. Practical applicability of the biocatalyst and transformation was illustrated by preparative scale synthesis of chiral intermediates of (S)-Tembamide, and (S)-Micanozole.

Photoisomerization and Light-Controlled Antibacterial Activity of Fluoroquinolone-Azoisoxazole Hybrids.

Photopharmacology holds a huge untapped potential to locally treat diseases involving photoswitchable drugs via the elimination of drugs' off-target effects. The growth of this field has created a pressing demand to develop such light-active drugs. We explored the potential for creating photoswitchable antibiotic hybrids by attaching pharmacophores norfloxacin/ciprofloxacin and azoisoxazole (photoswitch). All compounds exhibited a moderate to a high degree of bidirectional photoisomerization, long thermal cis half-lives, and impressive photoresistance. Gram-negative pathogens were found to be insensitive to these hybrids, while against Gram-positive pathogens, all hybrids in their trans states exhibited antibacterial activity that is comparable to that of the parent drugs. Notably, the toxicity of the irradiated hybrid 6 was found to be 2-fold lower than the nonirradiated trans isomer, indicating that the pre-inactivated cis-enriched drug can be employed for the site-specific treatment of bacterial infection using light, which could potentially eliminate the unwanted exposure of toxic antibiotics to both beneficial and untargeted harmful microbes in our body. Molecular docking revealed different binding affinity of the cis and trans isomers with the topoisomerase IV enzyme, due to their different shapes.

Photoswitchable Antibiotic Hybrids: Spacer Length-Dependent Photochemical Control of Antibacterial Activity.

Photopharmacology holds huge potential for the permanent (long-term) eradication of antibiotic resistance by the application of photoswitchable antibiotics. To construct such antibiotics, various methods have been employed to modify known antibiotics with photoswitches, such that the irradiated state shows activity comparable to or higher than that of the parent antibiotic and that a large activity difference between irradiated and nonirradiated states is achieved. However, most of those methods are ineffective when dealing with more than one drug with dissimilar structures. Here, we have demonstrated a new approach, in which two pharmacophores, one being a photoswitch, are covalently linked via a spacer of variable lengths, leading to a set of azopyrazole-norfloxacin antibiotic hybrids. All compounds showed a high degree of bidirectional photoisomerization, long thermal cis half-lives, and excellent photoresistance. Notably, the hybrid with an optimal four-carbon spacer length enabled the irradiated state to become 12-fold more potent than its nonirradiated state without losing much antimicrobial activity of norfloxacin. Only Gram-positive bacteria were found to be sensitive to this hybrid, and the full antibacterial potency of its irradiated state was found to be retained for nearly 24 h.

Climate change adaptation: Challenges for agricultural sustainability.

Climate change poses a substantial threat to agricultural sustainability globally. Agriculture is a vital component of the gross domestic production of developing countries. The multifaceted impacts of climate change on agriculture, highlighting how extreme weather events such as water stress, heatwaves, erratic rainfall, storms, floods, and emerging pest infestations are disrupting agricultural productivity. The socioeconomic status of farmers is particularly vulnerable to climatic extremes with future projections indicating significant increment in ambient air temperatures and unpredictable, intense rainfall patterns. Agriculture has historically relied on the extensive use of synthetic fertilizers, herbicides, and insecticides, combined with advancements in irrigation and biotechnological approaches to boost productivity. It encompasses a range of practices designed to enhance the resilience of agricultural systems, improve productivity, and reduce greenhouse gas emissions. By adopting climate-smart practices, farmers can better adapt to changing climatic conditions, thereby ensuring more sustainable and secure food production. Furthermore, it identifies key areas for future research, focusing on the development of innovative adaptation and mitigation strategies. These strategies are essential for minimizing the detrimental impacts of climate change on agriculture and for promoting the long-term sustainability of food systems. This article underscores the importance of interdisciplinary approaches and the integration of advanced technologies to address the challenges posed by climate change. By fostering a deeper understanding of these issues to inform policymakers, researchers, and practitioners about effective strategies to safeguard agricultural productivity and food security in the face of changing climate.

Direct Growth Control of Antibiotic-Resistant Bacteria Using Visible-Light-Responsive Novel Photoswitchable Antibiotics.

In addition to the discovery of new (modified) potent antibiotics to combat antibiotic resistance, there is a critical need to develop novel strategies that would restrict their off-target effects and unnecessary exposure to bacteria in our body and environment. We report a set of new photoswitchable arylazopyrazole-modified norfloxacin antibiotics that present a high degree of bidirectional photoisomerization, impressive fatigue resistance and reasonably high cis half-lives. The irradiated isomers of most compounds were found to exhibit nearly equal or higher antibacterial activity than norfloxacin against Gram-positive bacteria. Notably, against norfloxacin-resistant S. aureus bacteria, the visible-light-responsive p-SMe-substituted derivative showed remarkably high antimicrobial potency (MIC of 0.25 µg/mL) in the irradiated state, while the potency was reduced by 24-fold in case of its non-irradiated state. The activity was estimated to be retained for more than 7 hours. This is the first report to demonstrate direct photochemical control of the growth of antibiotic-resistant bacteria and to show the highest activity difference between irradiated and non-irradiated states of a photoswitchable antibiotic. Additionally, both isomers were found to be non-harmful to human cells. Molecular modellings were performed to identify the underlying reason behind the high-affinity binding of the irradiated isomer to topoisomerase IV enzyme.

Heat stress induced piRNA alterations in pachytene spermatocytes and round spermatids.

BACKGROUND: Spermatogenesis is a temperature-sensitive process, and elevation in temperature hampers this process quickly and significantly. We studied the molecular effects of testicular heating on piRNAs and gene expression in rat testicular germ cells. METHODS: We generated a cryptorchid rat model by displacing the testis from the scrotal sac (34 °C) to the abdominal area (37 °C) and sacrificed animals after 1 day, 3 days, and 5 days. Pachytene spermatocytes and round spermatids were purified using elutriation centrifugation and percoll gradient methods. We performed transcriptome sequencing in pachytene spermatocytes and round spermatids to identify differentially expressed piRNAs and their probable targets, i.e., TE transcripts and mRNAs. RESULTS: As a result of heat stress, we observed significant upregulation of piRNAs and TE transcripts in testicular germ cells. In addition to this, piRNA biogenesis machinery and heat shock proteins (Hsp70 and Hsp90 family members) were upregulated. mRNAs have also been proposed as targets for piRNAs; therefore, we shortlisted certain piRNA-mRNA pairs with an inverse relationship of expression. We observed that in testicular heat stress, the heat shock proteins go hand-in-hand with the upregulation of piRNA biogenesis machinery. The dysregulation of piRNAs in heat-stressed germ cells, increased ping-pong activity, and disturbed expression of piRNA target transcripts suggest a connection between piRNAs, mRNAs, and TE transcripts. CONCLUSIONS: In heat stress, piRNAs, piRNA machinery, and heat shock proteins are activated to deal with low levels of stress, which is followed by a rescue approach in prolonged stressaccompained by high TE activity to allow genetic mutations, perhaps for survival and adaptability.

Stilbenes: a journey from folklore to pharmaceutical innovation.

In modern times, medicine is predominantly based on evidence-based practices, whereas in ancient times, indigenous people relied on plant-based medicines with factual evidence documented in ancient books or folklore that demonstrated their effectiveness against specific infections. Plants and microbes account for 70% of drugs approved by the USFDA (U.S. Food and Drug Administration). Stilbenes, polyphenolic compounds synthesized by plants under stress conditions, have garnered significant attention for their therapeutic potential, bridging ancient wisdom with modern healthcare. Resveratrol, the most studied stilbene, initially discovered in grapes, red wine, peanuts, and blueberries, exhibits diverse pharmacological properties, including cardiovascular protection, antioxidant effects, anticancer activity, and neuroprotection. Traditional remedies, documented in ancient texts like the Ayurvedic Charak Samhita, foreshadowed the medicinal properties of stilbenes long before their modern scientific validation. Today, stilbenes are integral to the booming wellness and health supplement market, with resveratrol alone projected to reach a market value of 90 million US$ by 2025. However, challenges in stilbene production persist due to limited natural sources and costly extraction methods. Bioprospecting efforts reveal promising candidates for stilbene production, particularly endophytic fungi, which demonstrate high-yield capabilities and genetic modifiability. However, the identification of optimal strains and fermentation processes remains a critical consideration. The current review emphasizes the knowledge of the medicinal properties of Stilbenes (i.e., cardiovascular, antioxidant, anticancer, anti-inflammatory, etc.) isolated from plant and microbial sources, while also discussing strategies for their commercial production and future research directions. This also includes examples of novel stilbenes compounds reported from plant and endophytic fungi.

Suitably Incorporated Hydrophobic, Redox-Active Drug in Poly Lactic Acid-Graphene Nanoplatelet Composite Generates 3D-Printed Medicinal Patch for Electrostimulatory Therapeutics.

Polymer carbon composites have been reported for improved mechanical, thermal and electrical properties to provide reduced side effect by 3D printing personalized biomedical drug delivery devices. But control on homogeneity in loading and release of dopants like carbon allotropes and drugs, respectively, in the bulk and on the surface has always been a challenge. Herein, we are reporting a methodological cascade to achieve a model, customizable, 3D printed, homogeneously layered and electrically stimulatory, PLA-Graphene nanoplatelet (hl-PLGR) based drug delivery device, called 3D-est-MediPatch. The medicinal patch has been prepared by 3D-printing a Nic-hl-PLGR composite obtained by incorporating a redox active model drug, niclosamide (Nic) in hl-PLGR. The composite of Nic-hl-PLGR was characterized in three sequentially complex forms─composite film, hot melt extruded (HME) filament, and 3D printed (3DP) patches to understand the effect of filament extrusion and 3D-printing processes on Nic-hl-PLGR composite and overall drug incorporation efficiency and control. The incorporation of graphene was found to improve the homogeneity of the drug, and the hot melt extrusion improved the dispersion of drug and graphene fillers in the composite. The electroresponsive drug release from the Nic-hl-PLGR composite was found to be controllably accelerated compared to the drug release by diffusion, in simulated buffer condition. The released drug concentration was found to reach within the IC50 range for malignant melanoma cell (A375) and showed in vitro selectively, with reduced effects in noncancerous, fibroblast cells (NIH3T3). Further, the feasibility of application for this system was assessed in generating personalized 3D-est-MediPatch for skin, liver and spleen tissues in ex-vivo scenario. It showed excellent feasibility and efficacy of the 3D-est-MediPatch in controlled and personalized release of drugs during electrostimulation. Thus, a model platform, 3D-est-MediPatch, could be achieved by suitably incorporating a hydrophobic, redox-active drug (niclosamide) in poly lactic acid-graphene nanoplatelet composite for electrostimulatory therapeutics with reduced side effects.

Characterization of carotenoids extracted from Haloferax larsenii NCIM 5678 isolated from Pachpadra salt lake, Rajasthan.

Carotenoids are a diverse group of pigments known for their broad range of biological functions and applications. This study delves into multifaceted potential of carotenoids extracted from Haloferax larsenii NCIM 5678 previously isolated from Pachpadra Salt Lake in Rajasthan, India. H. larsenii NCIM 5678 was able to grow up to OD600 1.77 ± 0.03 with carotenoid concentration, 3.3 ± 0.03 µg/ml. The spectrophotometric analysis of carotenoid extract indicated the presence of three-fingered peak (460, 490 and 520 nm) which is a characteristic feature of bacterioruberin and its derivatives. The bacterioruberin was purified using silica gel column chromatography and thin layer chromatography. The carotenoid extract showed 12.3 ± 0.09 mm zone of growth inhibition with a minimum inhibitory concentration 546 ng/ml against indicator strain, H. larsenii HA4. The percentage antioxidant activity of carotenoid was found to be 84% which was higher as compared to commercially available ascorbic acid (56.74%). Thus, carotenoid extract from H. larsenii NCIM 5678 possesses unique attributes with compelling evidence of antimicrobial and antioxidant potential for the development of novel pharmaceuticals and nutraceuticals.

Microbial alcohol dehydrogenases: recent developments and applications in asymmetric synthesis.

Alcohol dehydrogenases are a well-known group of enzymes in the class of oxidoreductases that use electron transfer cofactors such as NAD(P)+/NAD(P)H for oxidation or reduction reactions of alcohols or carbonyl compounds respectively. These enzymes are utilized mainly as purified enzymes and offer some advantages in terms of green chemistry. They are environmentally friendly and a sustainable alternative to traditional chemical synthesis of bulk and fine chemicals. Industry has implemented several whole-cell biocatalytic processes to synthesize pharmaceutically active ingredients by exploring the high selectivity of enzymes. Unlike the whole cell system where cofactor regeneration is well conserved within the cellular environment, purified enzymes require additional cofactors or a cofactor recycling system in the reaction, even though cleaner reactions can be carried out with fewer downstream work-up problems. The challenge of producing purified enzymes in large quantities has been solved in large part by the use of recombinant enzymes. Most importantly, recombinant enzymes find applications in many cascade biotransformations to produce several important chiral precursors. Inevitably, several dehydrogenases were engineered as mere recombinant enzymes could not meet the industrial requirements for substrate and stereoselectivity. In recent years, a significant number of engineered alcohol dehydrogenases have been employed in asymmetric synthesis in industry. In a parallel development, several enzymatic and non-enzymatic methods have been established for regenerating expensive cofactors (NAD+/NADP+) to make the overall enzymatic process more efficient and economically viable. In this review article, recent developments and applications of microbial alcohol dehydrogenases are summarized by emphasizing notable examples.

Transition metal catalysed cascade C-C and C-O bond forming events of alkynes.

The past few decades have witnessed the emergence of domino reactions as a powerful tool for the multi-functionalization of alkynes for the rapid and smooth construction of complex molecular architectures. In this context, employing transition metal catalysis, vicinal/geminal cascade functionalization of alkynes involving C-C and C-O bond-formation reactions, has become a preferred strategy for the synthesis of oxygenated motifs. Despite this significant progress, reviews documenting such strategies are either metal/functional group-centric or target-oriented, thus hampering further developments. Therefore, in this review, different conceptual approaches based on C-C and C-O bond-forming events of alkynes such as carboxygenation (C-C and CO bond formation), carboalkoxylation (C-C and C-OR bond formation), and carboacetoxylation (C-C and C-OAc bond formations) are discussed, and examples from the literature from the last two decades are presented. Further, we have presented detailed insights into the mechanism of different transformations.

Are institutional deliveries equitable in the southern states of India? A benefit incidence analysis.

BACKGROUND: Despite a commendable rise in the number of women seeking delivery care at public health institutions in South India, it is unclear if the benefit accrues to wealthier or poorer socio-economic groups. The study's aim was to investigate at how the public subsidy is distributed among Indian women who give birth in public hospitals in the southern regions. METHODS: Data from the Indian Demographic Health Survey's fifth wave (NFHS-5, 2019-21) was used in this study. A total of 22, 403 were institutional deliveries across all the southern states of India were included. Out-of-pocket expenditure (OOPE) on childbirth in health institutions was the outcome variable. We used summary statistics, Benefits Incidence Analysis (BIA), concentration index (CI), and concentration curve (CC) were used. RESULTS: Most women in the lowest, poorest, and medium quintiles of wealth opted to give birth in public facilities. In contrast, about 69% of mothers belonging to highest quintile gave birth in private health institutions. The magnitude of CI and CC of institutional delivery indicates that public sector usage was concentrated among poorer quintiles [CIX: - 0.178; SE: 0.005; p < 0.001] and private sector usage was concentrated among wealthier quintiles [CIX: 0.239; SE: 0.006; p < 0.001]. Benefit incidence analyses suggest that middle quintile of women received the maximum public subsidy in primary health centres (33.23%), followed by richer quintile (25.62%), and poorer wealth quintiles (24.84%). These pattern in the secondary health centres was similar. CONCLUSION: Poorer groups utilize the public sector for institutional delivery in greater proportions than the private sector. Middle quintiles seem to benefit the most from public subsidy in terms of the median cost of service and non-payment. Greater efforts must be made to understand how and why these groups are being left behind and what policy measures can enhance their inclusion and financial risk protection.

Madhuca longifolia-hydro-ethanolic-fraction reverses mitochondrial dysfunction and modulates selective GLUT expression in diabetic mice fed with high fat diet.

BACKGROUND: Metabolic disorder is characterized as chronic low-grade inflammation which elevates the systemic inflammatory markers. The proposed hypothesis behind this includes occurrence of hypoxia due to intake of high fat diet leading to oxidative stress and mitochondrial dysfunction. AIM: In the present work our aim was to elucidate the possible mechanism of action of hydroethanolic fraction of M. longifolia leaves against the metabolic disorder. METHOD AND RESULTS: In the present investigation, effect of Madhuca longifolia hydroethanolic fraction (MLHEF) on HFD induced obesity and diabetes through mitochondrial action and selective GLUT expression has been studied. In present work, it was observed that HFD (50% of diet) on chronic administration aggravates the metabolic problems by causing reduced imbalanced oxidative stress, ATP production, and altered selective GLUT protein expression. Long term HFD administration reduced (p < 0.001) the SOD, CAT level significantly along with elevated liver function marker AST and ALT. MLHEF administration diminishes this oxidative stress. HFD administration also causes decreased ATP/ADP ratio owing to suppressed mitochondrial function and elevating LDH level. This oxidative imbalance further leads to dysregulated GLUT expression in hepatocytes, skeletal muscles and white adipose tissue. HFD leads to significant (p < 0.001) upregulation in GLUT 1 and 3 expression while significant (p < 0.001) downregulation in GLUT 2 and 4 expressions in WAT, liver and skeletal muscles. Administration of MLHEF significantly (p < 0.001) reduced the LDH level and also reduces the mitochondrial dysfunction. CONCLUSION: Imbalances in GLUT levels were significantly reversed in order to maintain GLUT expression in tissues on the administration of MLHEF.

Hot carrier dynamics in metalated porphyrin-naphthalimide thin films.

This study employs femtosecond transient absorption spectroscopy to investigate the rapid dynamics of excited state carriers in three metalated porphyrin-naphthalimide (PN) molecules and one free-base molecule. The dynamics of electron injection, from PN to mesoporous titania (TiO2), in PN adsorbed TiO2 films (Ti-PN), were carefully investigated and compared to PN adsorbed ZrO2 films (Zr-PN). In addition, we examined the self-assembled PN films and found that, in their self-assembled state, these molecules exhibited a longer relaxation time than Zr-PN monomeric films, where the charge injection channel was insignificant. The ground-state bleach band in the Ti-PN films gradually shifted to longer wavelengths, indicating the occurrence of the Stark effect. Faster electron injection was observed for the metalated PN systems and the electron injection times from the various excited states to the conduction band of TiO2 (CB-TiO2) were obtained from the target model analysis of the transient absorption spectra data matrix. In these metal-organic complexes, hot electron injection from PN to CB-TiO2 occurred on a time scale of <360 fs. Importantly, Cu(II)-based PN complexes exhibited faster injection and longer recombination times. The injection times have been estimated to result from a locally excited state at ≈280 fs, a hot singlet excited state at 4.95 ps, and a vibrationally relaxed singlet excited state at 97.88 ps. The critical photophysical and charge injection processes seen here provide the potential for exploring the underlying factors involved and how they correlate with photocatalytic performance.

Sulfur (Sâ ¥)-containing heterocyclic hybrids as antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA) and its SAR.

The discovery of new small molecule-based inhibitors is an attractive field in medicinal chemistry. Structurally diversified heterocyclic derivatives have been investigated to combat multi-drug resistant bacterial infections and they offers several mechanism of action. Methicillin-resistant Staphylococcus aureus (MRSA) is becoming more and more deadly to humans because of its simple method of transmission, quick development of antibiotic resistance, and ability to cause hard-to-treat skin and filmy diseases. The sulfur (SVI) particularly sulfonyl and sulfonamide based heterocyclic moieties, have found to be good anti-MRSA agents. The development of new nontoxic, economical and highly active sulfur (SVI) containing derivatives has become hot research topics in drug discovery research. Presently, more than 150 FDA approved Sulfur (SVI)-based drugs are available in the market, and they are widely used to treat various types of diseases with different therapeutic potential. The present collective data provides the latest advancements in Sulfur (SVI)-hybrid compounds as antibacterial agents against MRSA. It also examines the outcomes of in-vitro and in-vivo investigations, exploring potential mechanisms of action and offering alternative perspectives on the structure-activity relationship (SAR). Sulfur (SVI)-hybrids exhibits synergistic effects with existing drugs to provide antibacterial action against MRSA.

Bioproduction, purification, partial characterization and phenol removal efficacy of tyrosinase enzyme from Streptomyces sp. strain MR28.

The study focused on the production of the tyrosinase enzyme from Streptomyces sp. MR28 and its potency in removal of phenol content from water using free and immobilized tyrosinase enzyme. The tyrosinase was produced by Streptomyces sp. MR28 in liquid tyrosine broth medium, and it was further purified to near its homogeneity by employing, precipitation, dialysis, and column chromatography. After the purification, 44.49% yield with a 4 fold purification was achieved. The characterization of the purified enzyme showed a single major peak on HPLC and a solitary band on SDS-PAGE. The purified tyrosinase enzyme was active at a pH of 7.0 and a temperature of 30 °C. Further immobilization of purified tyrosinase was performed using the sodium alginate entrapment method. The capacity of the purified tyrosinase to remove phenol in water was evaluated by spectrophotometric method. The free tyrosinase enzyme-treated solutions showed a gradual decrease in the concentration of phenol with increased incubation time at 30 °C and 40 °C, at 90 min of the incubation time, it showed maximum efficacy in removing phenol from the solution. At 50 °C and 60 °C, the free tyrosinase enzyme exhibited very less capacity to remove the phenol. The immobilized enzyme showed good capacity for the removal of phenol from the solutions; the concentration of phenol in the solution decreased with an increase in the incubation time. At temperatures of 40 °C and 50 °C, the immobilized tyrosinase enzyme beads showed significant removal of phenol from the solution, and at temperatures of 30 °C and 60 °C, they also exhibited good capacity for the removal of phenol. At the end of the 90 min incubation period, it exhibited good capability. The current study suggests using immobilized microbial tyrosinase enzyme can be used for the removal of phenol from the contaminated water in a greener manner.