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One of the most fulminant and quickly spreading types of fungal infection, mucormycosis typically starts in the nose and paranasal sinuses after inhaling spores. Orbital and intracranial structures may become infected either directly or through blood vessels, leading to life-threatening complications. This infection most commonly manifests in the rhinomaxillary area, particularly in individuals with immunocompromised conditions like diabetes. Even with appropriate treatment, the disease’s mortality rate can exceed 40%, and it is challenging to detect. The standard treatment plan involves surgical debridement combined with systemically active antifungal medications, depending on the site of infection and risk factors. As a first-line treatment, lipid-based amphotericin B is recommended; however, posaconazole also shows promise. Hereby, the authors present a case report of a 15-year-old male patient with juvenile diabetes mellitus who had been experiencing pain and diffuse swelling in his left malar area for the previous two months. Following a histological analysis and clinical and radiographic evaluation by a multidisciplinary team, the patient was diagnosed with maxillary mucormycosis. Because of the abundant blood supply in the maxillofacial regions; however, more virulent fungi like Mucor can get past this obstacle. The purpose of present article is to show how early detection and treatment of mucormycosis in a young patient could prevent major morbidity and mortality from this potentially fatal illness . Additionally, it aimed to contribute to the local epidemiology of mucormycosis and raise awareness among stakeholders attention to the difficulties in treating this serious condition.

Among benign neoplasms of the salivary gland, malignancies are less common. One of the rarest tumours found in the oral cavity is oncocytoma, comprising less than 2% of all oral neoplasms and carrying a 1% risk of malignant transformation. Oncocytoma is rare among benign neoplasms, typically affecting females and impacting the major salivary glands. Literature discussing the cytodiagnosis of oncocytoma through Fine Needle Aspiration Cytology (FNAC) is even scarcer. Cytomorphological features indicating a predominantly oncocytic population with benign nuclear characteristics suggest the diagnosis of oncocytoma. The presence of oncocytes alongside other cell types in cytology smears suggests oncocytosis or a tumour-like presentation of Warthin’s tumour. Due to its unique features and clinical presentation, clinicians may misdiagnose this tumour as pleomorphic adenoma, haemangioma, or another form of oncocytosis due to its rarity and clinical features. Therefore, only histopathological examination can provide a definitive diagnosis. The present report discusses two unusual cytodiagnoses of oncocytoma identified through FNAC of the parotid gland in a 50-year-old female and a 70-year-old male, along with their clinicoradiological findings and subsequent tumour excision. Furthermore, the authors aim to raise awareness about the importance of a comprehensive work-up and optimal treatment selection for these lesions.

ABSTRACT Inositol pyrophosphate 1,5-IP8 regulates expression of a fission yeast phosphate homeostasis regulon, comprising phosphate acquisition genes pho1, pho84, and tgp1, via its action as an agonist of precocious termination of transcription of the upstream lncRNAs that repress PHO mRNA synthesis. 1,5-IP8 levels are dictated by a balance between the Asp1 N-terminal kinase domain that converts 5-IP7 to 1,5-IP8 and three inositol pyrophosphatases—the Asp1 C-terminal domain (a histidine acid phosphatase), Siw14 (a cysteinyl-phosphatase), and Aps1 (a Nudix enzyme). In this study, we report the biochemical and genetic characterization of Aps1 and an analysis of the effects of Asp1, Siw14, and Aps1 mutations on cellular inositol pyrophosphate levels. We find that Aps1’s substrate repertoire embraces inorganic polyphosphates, 5-IP7, 1-IP7, and 1,5-IP8. Aps1 displays a ~twofold preference for hydrolysis of 1-IP7 versus 5-IP7 and aps1∆ cells have twofold higher levels of 1-IP7 vis-à-vis wild-type cells. While neither Aps1 nor Siw14 is essential for growth, an aps1∆ siw14∆ double mutation is lethal on YES medium. This lethality is a manifestation of IP8 toxicosis, whereby excessive 1,5-IP8 drives derepression of tgp1, leading to Tgp1-mediated uptake of glycerophosphocholine. We were able to recover an aps1∆ siw14∆ mutant on ePMGT medium lacking glycerophosphocholine and to suppress the severe growth defect of aps1∆ siw14∆ on YES by deleting tgp1. However, the severe growth defect of an aps1∆ asp1-H397A strain could not be alleviated by deleting tgp1, suggesting that 1,5-IP8 levels in this double-pyrophosphatase mutant exceed a threshold beyond which overzealous termination affects other genes, which results in cytotoxicity.IMPORTANCERepression of the fission yeast PHO genes tgp1, pho1, and pho84 by lncRNA-mediated interference is sensitive to changes in the metabolism of 1,5-IP8, a signaling molecule that acts as an agonist of precocious lncRNA termination. 1,5-IP8 is formed by phosphorylation of 5-IP7 and catabolized by inositol pyrophosphatases from three distinct enzyme families: Asp1 (a histidine acid phosphatase), Siw14 (a cysteinyl phosphatase), and Aps1 (a Nudix hydrolase). This study entails a biochemical characterization of Aps1 and an analysis of how Asp1, Siw14, and Aps1 mutations impact growth and inositol pyrophosphate pools in vivo. Aps1 catalyzes hydrolysis of inorganic polyphosphates, 5-IP7, 1-IP7, and 1,5-IP8 in vitro, with a ~twofold preference for 1-IP7 over 5-IP7. aps1∆ cells have twofold higher levels of 1-IP7 than wild-type cells. An aps1∆ siw14∆ double mutation is lethal because excessive 1,5-IP8 triggers derepression of tgp1, leading to toxic uptake of glycerophosphocholine.

Introduction: Breast cancer is the most common malignant tumour and the leading cause of cancer-related death in women is breast cancer. The Immunohistochemistry (IHC) method utilised antigens and antibodies to interact to identify cellular or tissue constituents (antigens). This research has been employed as a diagnostic tool for specific cancers. When Programmed Cell Death Ligand 1 (PD-L1) binds to Programmed Cell Death 1 (PD-1), it suppresses the cellular immune response by killing and depleting T-cells. Monoclonal antibodies that block the PD-1/ PD-L1 pathway have shown promise as a treatment strategy currently being tested in human cancer trials. Need for the study: Breast cancer is a global issue, and PDL1 expression is emerging as a promising biomarker for breast cancer prognosis. It can provide valuable information treatment planning. Aim: The current study aims to examine the expression of PD-1 and PD-L1 in breast cancer using IHC in all subgroups of breast cancer patients. Both tests can serve as a biomarkers to guide immunotherapeutic interventions, improving prognosis, and correlating with other clinicopathological individual parameters such as age, tumour size, distant metastasis, lymph node involvement, Estrogen Receptor (ER) and Progesterone Receptor (PR) status, Her2neu expression, histological type, and TNM stage. Materials and Methods: This will be a two-year cohort study conducted in the Department of Pathology, Jawaharlal Nehru Medical College (JNMC), Maharashtra, India. The study will include 70 specimens from all cases with a histopathological diagnosis of breast cancer. The Nottingham variant of the Bloom-Richardson Grading System will be used to determine the histological grade of the tumour, and immunostaining for PD-1 and PD-L1 will be performed to evaluate their protein expression.

This manuscript elucidates new mechanisms of mutagenesis in mycobacteria by implicating two translesion DNA polymerases in genome diversification, including creating the mutations that underlie all antibiotic resistance in these global pathogens.

Translesion synthesis by translesion polymerases is a conserved mechanism of DNA damage tolerance. In bacteria, DinB enzymes are the widely distributed promutagenic translesion polymerases. The role of DinBs in mycobacterial mutagenesis was unclear until recent studies revealed a role for mycobacterial DinB1 in substitution and frameshift mutagenesis, overlapping with that of translesion polymerase DnaE2. Mycobacterium smegmatis encodes two additional DinBs (DinB2 and DinB3) and Mycobacterium tuberculosis encodes DinB2, but the roles of these polymerases in mycobacterial damage tolerance and mutagenesis is unknown. The biochemical properties of DinB2, including facile utilization of ribonucleotides and 8-oxo-guanine, suggest that DinB2 could be a promutagenic polymerase. Here, we examine the effects of DinB2 and DinB3 overexpression in mycobacterial cells. We demonstrate that DinB2 can drive diverse substitution mutations conferring antibiotic resistance. DinB2 induces frameshift mutations in homopolymeric sequences, both in vitro and in vivo. DinB2 switches from less to more mutagenic in the presence of manganese in vitro. This study indicates that DinB2 may contribute to mycobacterial mutagenesis and antibiotic resistance acquisition in combination with DinB1 and DnaE2.

There is a pressing need to identify recent directions in the field of aptamer-based sensing. DNA aptamers that are synthetically generated by in vitro selection mechanisms using the SELEX technique are single-stranded oligonucleotides which are selected to bind to a target with favorable sensitivity and selectivity. These aptamers have attracted significant attention due to their high binding affinity and ability to be easily engineered and provide various detection modes in what are known as aptasensors. Our aim is to focus on specialized detection strategies that have gained less attention but are of vital importance, such as optical detection in live cells, fluorescence polarization sensing, multi-analyte detection, colorimetric bioassays, wavelength shifting, and electrochemical-based detection. This will provide us with a perspective to facilitate developments in aptasensor technology for various targets, promising a bright future for biological receptors in the field of biosensing.

Growing evidence suggests that prebiotics may induce weight loss and alleviate non-alcoholic fatty liver disease (NAFLD) via modulation of the gut microbiota. However, key members of the gut microbiota that may mediate the beneficial effects of prebiotics remain elusive. Here, we find that restricted prebiotic feeding during active phase (HF-ARP) induced weight-independent alleviation of liver steatosis and reduced serum cholesterol in high-fat diet (HF) fed mice more significantly than unrestricted feeding (HF-UP). HF-ARP mice also showed concomitantly altered gut microbiota structure that was different from HF-UP group along with significantly increased production of total short-chain fatty-acids (SCFAs). Amplicon sequence variants (ASVs) were clustered into co-abundant groups (CAGs) as potential functional groups that may respond distinctively to prebiotic consumption and prebiotic feeding regime. Prebiotic feeding induces significant alterations in CAG abundances by day 7. Eight of 32 CAGs were promoted by prebiotics, including CAG17 with the most abundant ASV from Parabacteroides, CAG22 with Bacteroides thetaiotamicron and CAG32 with Fecalibaculum and Akkermansia. Among the prebiotic-promoted CAGs, CAG20 with ASVs from Lachnospiraceae and CAG21 with ASVs from Bifidobacterium and Lachnospiraceae were significantly enhanced in HF-ARP compared to HF-UP. Moreover, most of the prebiotic-promoted CAGs were also significantly associated with improvements in hepatic steatosis, reduction in serum cholesterol and increased cecal propionate production. Together, these results suggest that the impact of prebiotics on weight-independent alleviation of liver steatosis and cholesterol-lowering effect can be optimized by restricting prebiotic intake to active phase and is associated with a distinct change of gut microbiota with increased SCFA production.

Abstract Translation of genes is regulated by many factors including microRNAs (miRNAs). miRNA profiling of lesional and non-lesional epidermal RNA from 18 vitiligo patients revealed significant upregulation of 29 miRNAs in the lesional epidermis, of which 6 miRNAs were transfected in normal human epidermal keratinocytes (NHEKs) to study their downstream effects using quantitative proteomics. Many proteins involved in oxidative stress, Vesicle trafficking, Cellular apoptosis, Mitochondrial proteins and Keratins were regulated after miRNA transfections in the keratinocytes. However, tyrosinase related protein-1 (TRP1/TYRP1), a melanogenesis protein, was consistently downregulated in NHEKs by all the six miRNAs tested, which was quite intriguing. TRP1 was also downregulated in lesional epidermis compared with non-lesional epidermis. Since melanocytes synthesize and transfer melanosomes to the surrounding keratinocytes, we hypothesized that downregulation of TRP1 in NHEKs may have a role in melanosome transfer, which was confirmed by our co-culture experiments. Downregulation of TRP1 in keratinocytes negatively affected the melanosome transfer from melanocytes to keratinocytes resulting in melanin accumulation which may be leading to melanin induced cytotoxicity in melanocytes. Regulation of key processes involved in aetiopathogenesis of vitiligo along with TRP1 suggests that miRNAs act in an integrated manner which may be detrimental for the loss of melanocytes in vitiligo.

A simple optical aptasensor has been synthesized for the detection of calcium ions. This sensing approach employs a semiconductor quantum dot (QD)–gold nanoparticle as the donor–quencher pair and operates on the principle of fluorescence resonant energy transfer (FRET). On binding with calcium ions, the DNA aptamer undergoes a conformational change, which changes the distance between the quantum dot and the gold nanoparticle, conjugated on the 5′ terminal and 3′ terminal of the aptamer, respectively. This phenomenon results in the quenching of the quantum dot emission. In this sensor, a maximum quenching of 22.42 ± 0.71% has been achieved at 35 nM calcium ion concentration while the limit of detection has been determined to be 3.77 pM. The sensor has been found to have high specificity for calcium ions in comparison to other metal ions like sodium, magnesium, and potassium. The molecular apta-beacons also demonstrated successful endocytosis and FRET-based calcium ion detection in osteocyte cells when conjugated with a cell-penetrating peptide (DSS).

Plumbagin derived from the plant Plumbago indica, known as Chitrak in India, is an example of a medicinal compound used traditionally to cure a variety of ailments. Previous reports have indicated that it can inhibit the growth of Mycobacterium tuberculosis (Mtb), the causative agent of the deadly disease TB. In this investigation, we provide an insight into its mode of action. We show here that a significant mycobacterial target that is inhibited by plumbagin is the enzyme ThyX, a form of thymidylate synthase, that is responsible for the synthesis of dTMP from dUMP in various bacterial pathogens, including Mtb. Using a purified preparation of the recombinant version of Mtb ThyX, we demonstrate that plumbagin, a 2,4 napthoquinone, but not lawsone, a structurally related medicinal compound, inhibits its activity in vitro. We also show that the intracellular [dTTP]/[dATP] ratio in Mycobacterium smegmatis (Msm) cells decrease upon treatment with plumbagin, and this, in turn, leads to cell death. Such a conclusion is supported by the observation that over-expression of thyx in the plumbagin treated Msm cells leads to the restoration of viability. The results of our investigation indicate that plumbagin kills mycobacterial cells primarily by targeting ThyX, a vital enzyme required for their survival.

Polycyclic aromatic hydrocarbons (PAHs) include a group of organic priority pollutants of critical environmental and public health concern due to their toxic, genotoxic, mutagenic and/or carcinogenic properties and their ubiquitous occurrence as well as recalcitrance. The increased awareness of their various adverse effects on ecosystem and human health has led to a dramatic increase in research aimed towards removing PAHs from the environment. PAHs may undergo adsorption, volatilization, photolysis, and chemical oxidation, although transformation by microorganisms is the major neutralization process of PAH-contaminated sites in an ecologically accepted manner. Microbial degradation of PAHs depends on various environmental conditions, such as nutrients, number and kind of the microorganisms, nature as well as chemical property of the PAH being degraded. A wide variety of bacterial, fungal and algal species have the potential to degrade/transform PAHs, among which bacteria and fungi mediated degradation has been studied most extensively. In last few decades microbial community analysis, biochemical pathway for PAHs degradation, gene organization, enzyme system, genetic regulation for PAH degradation have been explored in great detail. Although, xenobiotic-degrading microorganisms have incredible potential to restore contaminated environments inexpensively yet effectively, but new advancements are required to make such microbes effective and more powerful in removing those compounds, which were once thought to be recalcitrant. Recent analytical chemistry and genetic engineering tools might help to improve the efficiency of degradation of PAHs by microorganisms, and minimize uncertainties of successful bioremediation. However, appropriate implementation of the potential of naturally occurring microorganisms for field bioremediation could be considerably enhanced by optimizing certain factors such as bioavailability, adsorption and mass transfer of PAHs. The main purpose of this review is to provide an overview of current knowledge of bacteria, halophilic archaea, fungi and algae mediated degradation/transformation of PAHs. In addition, factors affecting PAHs degradation in the environment, recent advancement in genetic, genomic, proteomic and metabolomic techniques are also highlighted with an aim to facilitate the development of a new insight into the bioremediation of PAH in the environment.