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Four food toxins, α-oxo-aldehydes (glyoxal and Methylglyoxal) and furfurals (furfural and 5-hydroxymethlfurfural) were simultaneously retained on a Phenomenex Luna phenyl hexyl column (150×4.6mm×5 µm,100 Å) using ammonium acetate / acetonitrile (28:72, v/v) as mobile phase at 1 mL/min. The detector setting was tuned at 280 nm to quantify furfurals, whereas α-oxo-aldehydes were quantified using Evaporating light scattering detector (ELSD). The extraction of selected analytes from aqueous and lipid-based media was optimized using liquid-liquid extraction (LLE) method. A sum of 24 different brands (n = 20 in each group) of glucose containing preparations were collected, extracted, and screened for the presence of selected analytes. The observed level of selected analytes was divided into non-detectable, moderately high and above limit samples. The machine learning model viz. decision tree and multilayer perceptron models was optimized and validated for correlation of selected dependent variables with independent variables. The occurrence of 5-HMF depended on state and age of sample, whereas sugar concentration was responsible for furfural presence. The samples with higher 5-HMF levels were categorized as being viscous/semisolid and were preserved with potassium sorbate. About 77.3 % of the 480 samples studied indicated a considerable amount of methylglyoxal, and the food colors were classed as responsible for development of it followed by mixed fruit flavor and vanilla taste flavor as food additives.

The Tarantula Nebula in the Large Magellanic Cloud is known for its high star formation activity. At its center lies the young massive star cluster R136, providing a significant amount of the energy that makes the nebula shine so brightly at many wavelengths. Recently, young massive star clusters have been suggested to also efficiently produce very high-energy cosmic rays, potentially beyond PeV energies. Here, we report the detection of very-high-energy γ -ray emission from the direction of R136 with the High Energy Stereoscopic System, achieved through a multicomponent, likelihood-based modeling of the data. This supports the hypothesis that R136 is indeed a very powerful cosmic-ray accelerator. Moreover, from the same analysis, we provide an updated measurement of the γ -ray emission from 30 Dor C, the only superbubble detected at TeV energies presently. The γ -ray luminosity above 0.5 TeV of both sources is (2–3) × 10 ^35 erg s ^−1 . This exceeds by more than a factor of 2 the luminosity of HESS J1646−458, which is associated with the most massive young star cluster in the Milky Way, Westerlund 1. Furthermore, the γ -ray emission from each source is extended with a significance of >3 σ and a Gaussian width of about 30 pc. For 30 Dor C, a connection between the γ -ray emission and the nonthermal X-ray emission appears likely. Different interpretations of the γ -ray signal from R136 are discussed.

GRB 221009A is the brightest gamma-ray burst (GRB) ever detected. To probe the very-high-energy (VHE; >100 GeV) emission, the High Energy Stereoscopic System (H.E.S.S.) began observations 53 hr after the triggering event, when the brightness of the moonlight no longer precluded observations. We derive differential and integral upper limits using H.E.S.S. data from the third, fourth, and ninth nights after the initial GRB detection, after applying atmospheric corrections. The combined observations yield an integral energy flux upper limit of ${{\rm{\Phi }}}_{\mathrm{UL}}^{95 \% }=9.7\times {10}^{-12}\,\mathrm{erg}\,{\mathrm{cm}}^{-2}\,{{\rm{s}}}^{-1}$ above E _thr = 650 GeV. The constraints derived from the H.E.S.S. observations complement the available multiwavelength data. The radio to X-ray data are consistent with synchrotron emission from a single electron population, with the peak in the spectral energy distribution occurring above the X-ray band. Compared to the VHE-bright GRB 190829A, the upper limits for GRB 221009A imply a smaller gamma-ray to X-ray flux ratio in the afterglow. Even in the absence of a detection, the H.E.S.S. upper limits thus contribute to the multiwavelength picture of GRB 221009A, effectively ruling out an IC-dominated scenario.

In 2021 July, PKS 1510−089 exhibited a significant flux drop in the high-energy γ -ray (by a factor 10) and optical (by a factor 5) bands and remained in this low state throughout 2022. Similarly, the optical polarization in the source vanished, resulting in the optical spectrum being fully explained through the steady flux of the accretion disk and the broad-line region. Unlike the aforementioned bands, the very-high-energy γ -ray and X-ray fluxes did not exhibit a significant flux drop from year to year. This suggests that the steady-state very-high-energy γ -ray and X-ray fluxes originate from a different emission region than the vanished parts of the high-energy γ -ray and optical jet fluxes. The latter component has disappeared through either a swing of the jet away from the line of sight or a significant drop in the photon production efficiency of the jet close to the black hole. Either change could become visible in high-resolution radio images.

Magnetic fields in galaxies and galaxy clusters are believed to be the result of the amplification of intergalactic seed fields during the formation of large-scale structures in the universe. However, the origin, strength, and morphology of this intergalactic magnetic field (IGMF) remain unknown. Lower limits on (or indirect detection of) the IGMF can be obtained from observations of high-energy gamma rays from distant blazars. Gamma rays interact with the extragalactic background light to produce electron−positron pairs, which can subsequently initiate electromagnetic cascades. The gamma-ray signature of the cascade depends on the IGMF since it deflects the pairs. Here we report on a new search for this cascade emission using a combined data set from the Fermi Large Area Telescope and the High Energy Stereoscopic System. Using state-of-the-art Monte Carlo predictions for the cascade signal, our results place a lower limit on the IGMF of B > 7.1 × 10 ^−16 G for a coherence length of 1 Mpc even when blazar duty cycles as short as 10 yr are assumed. This improves on previous lower limits by a factor of 2. For longer duty cycles of 10 ^4 (10 ^7 ) yr, IGMF strengths below 1.8 × 10 ^−14 G (3.9 × 10 ^−14 G) are excluded, which rules out specific models for IGMF generation in the early universe.

We report on multiwavelength target-of-opportunity observations of the blazar PKS 0735+178, located 2.°2 away from the best-fit position of the IceCube neutrino event IceCube-211208A detected on 2021 December 8. The source was in a high-flux state in the optical, ultraviolet, X-ray, and GeV γ -ray bands around the time of the neutrino event, exhibiting daily variability in the soft X-ray flux. The X-ray data from Swift-XRT and NuSTAR characterize the transition between the low-energy and high-energy components of the broadband spectral energy distribution (SED), and the γ -ray data from Fermi-LAT, VERITAS, and H.E.S.S. require a spectral cutoff near 100 GeV. Both the X-ray and γ -ray measurements provide strong constraints on the leptonic and hadronic models. We analytically explore a synchrotron self-Compton model, an external Compton model, and a lepto-hadronic model. Models that are entirely based on internal photon fields face serious difficulties in matching the observed SED. The existence of an external photon field in the source would instead explain the observed γ -ray spectral cutoff in both the leptonic and lepto-hadronic models and allow a proton jet power that marginally agrees with the Eddington limit in the lepto-hadronic model. We show a numerical lepto-hadronic model with external target photons that reproduces the observed SED and is reasonably consistent with the neutrino event despite requiring a high jet power.

ABSTRACT Microhabitat factors associated with the habitat of barking deer (Muntiacus vaginalis) were examined and compared between summer and winter seasons. Habitat characteristics and preferred habitat were measured by locating direct and indirect signs. To quantify the habitat utilization of barking deer, each selected study site was sampled for floral diversity from 2015 to 2017. Quadrats were deployed along transect lines to determine seasonal distribution. Barking deer were not evenly distributed across vegetation types in the study area; they occurred more often in the broad-leaved forest than in Chir pine forest, at an elevational range of 550-850 m, in thick vegetation on steep slopes. The most preferred habitat included trees and shrubs with 30% and 69% cover, respectively. Barking deer avoided thicker tree cover, possibly as it hinders movement and escape from predators. No significant difference (χ2 = 6.37, df = 3, p = 0.19) in seasonal vegetation cover was recorded.

Most species of pheasants (Galliformes: Phasianidae) occur in Asia. In Pakistan, pheasants occur from 245-3050 m in altitude, and one of these, the Kalij pheasant (Lophura leucomelanos) is a large-bodied, brightly-colored habitat quality indicator species. The present study was designed to determine spatiotemporal variation, population size, and the relative abundance of Kalij pheasants in Haripur, Pakistan. The line transects and point count methods were used to collect direct (physical observations) and indirect signs (feathers and calls) to avoid double counting. Twenty field surveys were conducted along 16 transects with an area of 0.811 km2 in 4 study sites to quantify habitat utilization of Kalij pheasant. Kalij pheasant activities were observed at the start of dawn (0600 hours to 0730 hours) and ended by 1630 hours to 1800 hours dusk period with only a few sightings during the middle of the day. Study sites were selected based on confirmation of presence signs. Twenty-seven individuals with direct (16) and indirect (feather = 5, calls = 6) signs were encountered while walking along line transects. Twelve signs were counted (sightings = 3, Calls = 9) within the radius of 11-50 m in the point count method. Results showed that the Kalij pheasant occupied scrub forest with dense vegetation between 500-1100m away. The mean encounter rate of the Kalij pheasant was 0.82/km, which was higher from July to September. The sex ratio (1.17) is biased toward males in the overall population of Kalij pheasants. The estimated mean density of the Kalij pheasant in Haripur was 6.97 animals/km2, and the total abundance was 142 individuals. New potential sites may be identified and declared as protected areas, and awareness and support of the local community are recommended for the protection and management of the Kalij pheasant., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Saba et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The cerebellum, a key target of ethanol's toxic effects, is associated with ataxia following alcohol consumption. However, the impact of ethanol on Purkinje cell (PC) mitochondria remains unclear. To investigate how ethanol administration affects mitochondrial dynamics in cerebellar Purkinje cells, we employed a transgenic mouse model expressing mitochondria-targeted yellow fluorescent protein in Purkinje cells (PC-mito-eYFP). Both male and female PC-mito-eYFP mice received an intraperitoneal injection of ethanol or vehicle. One hour after ethanol administration, the animals were perfusion fixed or their cerebellum tissue or isolated mitochondria were collected. Cerebellum sections were analyzed using confocal microscopy to assess changes in mitochondrial length distribution. In vivo superoxide levels were measured using dihydroethidium (DHE), and mitochondrial NAD levels were determined by high-performance liquid chromatography (HPLC). Our findings revealed a sex-dependent response to ethanol administration in mitochondrial size distribution. While male Purkinje cell mitochondria exhibited no significant changes in size, female mitochondria became more fragmented after one hour of ethanol administration. This coincided with elevated phosphorylation of the fission protein Drp1 and increased superoxide production, as measured by DHE fluorescence intensity. Similarly, mitochondrial NAD levels were significantly reduced in female mice, but no changes were observed in males. Our results demonstrate that ethanol induced mitochondrial fragmentation through increased free radical levels, due to reduced NAD and increased p-Drp1, in PC cells of the female cerebellum.

One of the most prominent challenges related to the management of diabetes is a diabetic foot ulcer (DFU). It has been noted that > 50% of ulcers become clinically infected in diabetic patients, and up to 15-25% of diabetic patients may acquire DFU in their lifetime. DFU treatment is complicated for immune-compromised individuals and has a low success rate. Therefore, diabetic foot care must begin as soon as possible to avoid negative outcomes such as significant social, psychological, and economic consequences, lower limb amputation, morbidity, and mortality. The information provided in this piece is crucial for assisting clinicians and patients regarding novel and cutting-edge treatments for DFU. Due to irrational recourse to antibiotics, etiological agents like bacteria and fungi are exhibiting multidrug resistance (MDR), making topical antibiotic treatments for wounds ineffective with the drugs we currently have. This review article aims to compile the various strategies presently in use for managing and treating DFUs. The piece covers topics like biofilm, diagnosis, drug resistance, multidisciplinary teamwork, debridement, dressings, offloading, negative pressure therapy, topical antibiotics, surgery, cell and gene therapy, and other cutting-edge therapies., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Association of Microbiologists of India 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Owing to their rapid cooling rate and hence loss-limited propagation distance, cosmic-ray electrons and positrons (CRe) at very high energies probe local cosmic-ray accelerators and provide constraints on exotic production mechanisms such as annihilation of dark matter particles. We present a high-statistics measurement of the spectrum of CRe candidate events from 0.3 to 40 TeV with the High Energy Stereoscopic System, covering 2 orders of magnitude in energy and reaching a proton rejection power of better than 10^{4}. The measured spectrum is well described by a broken power law, with a break around 1 TeV, where the spectral index increases from Γ_{1}=3.25±0.02(stat)±0.2(sys) to Γ_{2}=4.49±0.04(stat)±0.2(sys). Apart from the break, the spectrum is featureless. The absence of distinct signatures at multi-TeV energies imposes constraints on the presence of nearby CRe accelerators and the local CRe propagation mechanisms.

Introduction: Healthcare amelioration is exponential to technological advancement. In the recent era of automation, the consolidation of artificial intelligence (AI) in dentistry has rendered transformation in oral healthcare from a hardware-centric approach to a software-centric approach, leading to enhanced efficiency and improved educational and clinical outcomes., Objectives: The aim of this narrative overview is to extend the succinct of the major events and innovations that led to the creation of modern-day AI and dentistry and the applicability of the former in dentistry. This article also prompts oral healthcare workers to endeavor a liable and optimal approach for effective incorporation of AI technology into their practice to promote oral health by exploring the potentials, constraints, and ethical considerations of AI in dentistry., Methods: A comprehensive approach for searching the white and grey literature was carried out to collect and assess the data on AI, its use in dentistry, and the associated challenges and ethical concerns., Results: AI in dentistry is still in its evolving phase with paramount applicabilities relevant to risk prediction, diagnosis, decision-making, prognosis, tailored treatment plans, patient management, and academia as well as the associated challenges and ethical concerns in its implementation., Conclusion: The upsurging advancements in AI have resulted in transformations and promising outcomes across all domains of dentistry. In futurity, AI may be capable of executing a multitude of tasks in the domain of oral healthcare, at the level of or surpassing the ability of mankind. However, AI could be of significant benefit to oral health only if it is utilized under responsibility, ethicality and universality., Competing Interests: Balaj Khalid is currently affiliated with Viterbi School of Engineering, University of Southern California The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

A 17 year female came with complaints of swelling over left lateral wall of nose and left nasal block was found to have osteochondroma of maxilla on CT PNS, resected by sub labial approach with postoperative histopathological confirmation. Thus describing a rare case of osteochondroma of maxilla treated without any cosmetic and functional impairment., Competing Interests: Competing interestsNone., (© Association of Otolaryngologists of India 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Reducing sugars causes confirmatory alterations in albumin structure by the nonenzymatic glycation of the amino group of serum albumin. In this study, glucose and its hazardous metabolic products like glyoxal and methylglyoxal were incubated with bovine serum albumin (BSA). The confirmational changes in BSA molecule's structure by glycating substances was investigated using a variety of spectroscopic methods, including deconvolutionFourier Transform Infra-red (FT-IR) spectroscopy, fluorescence spectroscopy, UV spectroscopy and circular dichroism (CD) spectroscopy. Dynamic fluorescence quenching was observed in the case of glucose, while static quenching was observed in the case of methyl glyoxal and glyoxal. Similarly, employing deconvolution FT-IR spectroscopy and CD spectroscopy for determination of change in secondary structures in terms signature of α-helix, β-turn, β-sheet and random coil modifications. Destabilization or unfolding of the albumin structure, due to the disruption of the hydrogen bonding pattern that stabilizes the albumin manifold, causes a 25-50% reduction in α-helix and a 2-fold increase in β-sheet and turns in glycated BSA. The competitive displacement interaction studies with warfarin were performed using the ultrafiltration technique and quantitative determination of free drug in ultrafiltrate using LC-MS/MS. The binding of carbamazepine (CBZ) or its active metabolite to proteins was unaffected by the glycation of BSA with glucose and methyl glyoxal. Nevertheless, with glyoxal-modified BSA, it changed the binding of selected analytes significantly. Based on in vitro observations and results, it could be anticipated that the serum CBZ concentration variation may be worsened in uncontrolled diabetes circumstances, with an overall variance of 30-40% possible.Communicated by Ramaswamy H. Sarma.

SS 433 is a microquasar, a stellar binary system that launches collimated relativistic jets. We observed SS 433 in gamma rays using the High Energy Stereoscopic System (H.E.S.S.) and found an energy-dependent shift in the apparent position of the gamma-ray emission from the parsec-scale jets. These observations trace the energetic electron population and indicate that inverse Compton scattering is the emission mechanism of the gamma rays. Our modeling of the energy-dependent gamma-ray morphology constrains the location of particle acceleration and requires an abrupt deceleration of the jet flow. We infer the presence of shocks on either side of the binary system, at distances of 25 to 30 parsecs, and that self-collimation of the precessing jets forms the shocks, which then efficiently accelerate electrons.

With the miniaturization and integration of electronic components in wireless communication and wearable devices, the demand for low-cost flexible composites with temperature-stable high dielectric constant and low loss has substantially increased. However, such comprehensive properties are fundamentally difficult to combine for conventional conductive and ceramic composites. Here, we develop silicone elastomer (SE) composites based on hydrothermally grown MoS 2 on tissue paper-derived cellulose carbon (CC). Such design promoted the formation of microcapacitors, multiple interfaces, and defects reinforcing interfacial and defect polarizations and resulting in a high dielectric constant of 9.83 at 10 GHz with low filler loading of 15 wt %. Unlike highly conductive fillers, MoS 2 @CC with low conductivity ensured a very low loss tangent of 7.6 × 10 -3 , which was also influenced by the filler dispersion and adhesion to the matrix. Apart from breaking the typical conflict between high dielectric constant and low losses of traditional conductive composites, MoS 2 @CC SE composites were highly flexible with temperature-stable dielectric properties making them attractive as flexible substrates in microstrip antenna applications and extreme environment electronics. Moreover, recycling from waste tissue paper makes them potential candidates as low-cost and sustainable dielectric composites.

The mitochondrion has a unique position among other cellular organelles due to its dynamic properties and symbiotic nature, which is reflected in an active exchange of metabolites and cofactors between the rest of the intracellular compartments. The mitochondrial energy metabolism is greatly dependent on nicotinamide adenine dinucleotide (NAD) as a cofactor that is essential for both the activity of respiratory and TCA cycle enzymes. The NAD level is determined by the rate of NAD synthesis, the activity of NAD-consuming enzymes, and the exchange rate between the individual subcellular compartments. In this review, we discuss the NAD synthesis pathways, the NAD degradation enzymes, and NAD subcellular localization, as well as NAD transport mechanisms with a focus on mitochondria. Finally, the effect of the pathologic depletion of mitochondrial NAD pools on mitochondrial proteins' post-translational modifications and its role in neurodegeneration will be reviewed. Understanding the physiological constraints and mechanisms of NAD maintenance and the exchange between subcellular compartments is critical given NAD's broad effects and roles in health and disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder; however, its etiology remains elusive. Antioxidants are considered to be a promising approach for decelerating neurodegenerative disease progression owing to extensive examination of the relationship between oxidative stress and neurodegenerative diseases. In this study, we investigated the therapeutic effect of melatonin against rotenone-induced toxicity in the Drosophila model of PD. The 3-5 day old flies were divided into four groups: control, melatonin alone, melatonin and rotenone, and rotenone alone groups. According to their respective groups, flies were exposed to a diet containing rotenone and melatonin for 7 days. We found that melatonin significantly reduced the mortality and climbing ability of Drosophila because of its antioxidative potency. It alleviated the expression of Bcl 2, tyrosine hydroxylase (TH), NADH dehydrogenase, mitochondrial membrane potential, and mitochondrial bioenergetics and decreased caspase 3 expression in the Drosophila model of rotenone-induced PD-like symptoms. These results indicate the neuromodulatory effect of melatonin, and that it is likely modulated against rotenone-induced neurotoxicity by suppressing oxidative stress and mitochondrial dysfunctions., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Introduction: Globally, the prevalence of self-medication among young people has increased exponentially. Due to the basic knowledge and easy access to medicines, undergraduate students at health science colleges are likely to self-medicate. This research was undertaken to assess self-medication prevalence and its contributing factors among female undergraduate students in health science colleges at Majmaah University, Saudi Arabia., Materials and Methods: A descriptive, cross-sectional study involving 214 female students from the Majmaah University in Saudi Arabia's health science colleges-Medical: (82, 38.31%) and Applied Medical Science College (132, 61.68%)-was conducted. A self-administered questionnaire with sociodemographic information, drugs used, and reasons for self-medication was used for the survey. Non-probability sampling techniques were used to recruit participants., Results: Of the 214 female participants, 173, 80.84 % (medical: 82, 38.31% and applied medical science: 132, 61.68%) confirmed that they were on self-medication. The majority of participants (42.1%) were between the ages of 20 and 21.5 years (mean ± SD: 20.81 ± 1.4). The main reasons for self-medication were quick relief from the illness (77.5%) followed by saving time (76.3%), minor illnesses (71.1%), self-confidence (56.7%), and laziness (56.7%). The use of leftover drugs at home was common among applied medical science students (39.9%). The main indication for self-medication included menstrual problems (82.7 %), headache (79.8%), fever (72.8%), pain (71.1%), and stress (35.3%). The most common drugs used included antipyretic and analgesics (84.4%), antispasmodics (78.9%), antibiotics (76.9%), antacids (68.2%), multivitamins, and dietary supplements (66.5%). On the contrary, the least used drugs were antidepressants, anxiolytics, and sedatives (3.5, 5.8, and 7.5 %, respectively). Family members were the main source of information for self-medication (67.1%), followed by self-acquired knowledge (64.7%), social media (55.5%), and least were friends (31.2%). For adverse effects of the medication, the majority of them consulted the physician (85%) followed by consulting the pharmacist (56.7%) and switched to other drugs or decreased drug dosage. Quick relief, saving time, and minor illness were the main reasons for self-medication among health science college students. It is recommended to conduct awareness programs, workshops, and seminars to educate on the benefits and adverse effects of self-medication., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Loni, Eid Alzahrani, Alzahrani, Khan, Khatoon, Abdelrahman, Abd-Elhaleem and Alhaidari.)

Purpose: Meibomian carcinoma is a rare and aggressive malignant neoplasm of the eyelids. The clinical presentation often mimics benign conditions thereby making the diagnosis challenging. The aim of the study was to analyze cases of meibomian carcinoma, the specimens of which were received, in the past 2 years in the pathology department., Methods: This retrospective observational study was undertaken for 2 years and included 9 patients of meibomian carcinoma. For each case, detailed history and clinical findings were retrieved from the hospital records. Histopathological examination was undertaken in all cases after preparing hematoxylin and eosin-stained slides from tissue blocks preserved in the department., Results: The mean age of the patients was 55 ± 15 years. Six (66.7%) patients were females, and the other three (33.3%) were male. Following surgery, gross examination of the specimens revealed that the mean size of the excised tumors was 2.45 ± 1.45 cm. The tumors were classified based on histopathological features according to growth pattern, cell type, and cytoarchitecture. Most cases had lobular growth pattern (5, 55.6% cases), consisted of epidermoid cells (5, 55.6% cases), and exhibited infiltrative cytoarchitecture (8, 88.9% cases)., Conclusion: Early diagnosis of meibomian carcinoma is important to reduce mortality from the aggressive tumor. The knowledge of clinicopathological aspects of the tumors that were biopsied in the department of pathology in the past 2 years will help in diagnosis and management of such tumors in future., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Middle East African Journal of Ophthalmology.)

The last decade has witnessed the rise of an extremely threatening healthcare-associated multidrug-resistant non-albicans Candida (NAC) species, Candida auris. Since besides target alterations, efflux mechanisms contribute maximally to antifungal resistance, it is imperative to investigate their contributions in this pathogen. Of note, within the major facilitator superfamily (MFS) of efflux pumps, drug/H + antiporter family 1 (DHA1) has been established as a predominant contributor towards xenobiotic efflux. Our study provides a complete landscape of DHA1 transporters encoded in the genome of C. auris. This study identifies 14 DHA1 transporters encoded in the genome of the pathogen. We also construct deletion and heterologous overexpression strains for the most important DHA1 drug transporter, viz., CauMdr1 to map the spectrum of its substrates. While the knockout strain did not show any significant changes in the resistance patterns against most of the tested substrates, the ortholog when overexpressed in a minimal background Saccharomyces cerevisiae strain, AD1-8u - , showed significant enhancement in the minimum inhibitory concentrations (MICs) against a large panel of antifungal molecules. Altogether, the present study provides a comprehensive template for investigating the role of DHA1 members of C. auris in antifungal resistance mechanisms. KEY POINTS: • Fourteen putative DHA1 transporters are encoded in the Candida auris genome. • Deletion of the CauMDR1 gene does not lead to major changes in drug resistance. • CauMdr1 recognizes and effluxes numerous xenobiotics, including prominent azoles., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Androgens are endogenous hormones that play a crucial role in the paracrine and intracrine hormone system to perform and maintain vital physiological functions. Altered levels of androgens are implicated in many diseases such as sexual dysregulation, breast cancer, prostate cancer, and heart diseases etc. In this manuscript we describe a liquid chromatography-mass spectrometry (LC-MS) method using multiple reaction monitoring (MRM) for quantitatively measuring specific androgens such as dehydroepiandrosterone, testosterone, androsterone sulphate, androstenedione, and dihydrotestosterone in serum and urine samples. Serum acquired from nine different subjects (three pre-menopausal women, three postmenopausal women, and three healthy males) were used to evaluate the developed methods. In the sample preparation methods for serum either protein precipitation or liquid-liquid extraction (LLE) was used while the analysis of urinary androgens used LLE. The extracted androgens were quantitatively measured using LC-MRM-MS to which known amounts of stable isotope labeled standards were added. This manuscript also presents a LC-MRM-MS method mode for the analysis of oxime derivatized androgens potentially to enhance the sensitivity of the assay if required, from urine and venous-drawn serum samples., (Published by Elsevier Inc.)

The peptide transport (PTR) or proton-dependent oligopeptide transporter (POT) family exploits the inwardly directed proton motive force to facilitate the cellular uptake of di/tripeptides. Interestingly, some representatives are also shown to import peptide-based antifungals in certain Candida species. Thus, the identification and characterization of PTR transporters serve as an essential first step for their potential usage as antifungal peptide uptake systems. Herein, we present a genome-wide inventory of the PTR transporters in five prominent Candida species. Our study identifies 2 PTR transporters each in C. albicans and C. dubliniensis, 1 in C. glabrata, 4 in C. parapsilosis, and 3 in C. auris. Notably, despite all representatives retaining the conserved features seen in the PTR family, there exist two distinct classes of PTR transporters that differ in terms of their sequence identities and lengths of certain extracellular and intracellular segments. Further, we also evaluated the contribution of each PTR protein of the newly emerged multi-drug-resistant C. auris in di/tripeptide uptake. Notably, deletion of two PTR genes BNJ08_003830 and BNJ08_005124 led to a marked reduction in the transport capabilities of several tested di/tripeptides. However, all three genes could complement the role of native PTR2 gene of Saccharomyces cerevisiae, albeit to varied levels. Besides, BNJ08_005124 deletion also resulted in increased resistance toward the peptide-nucleoside drug Nikkomycin Z as well as the glucosamine-6-phosphate synthase inhibitor, L-norvalyl-N3-(4-methoxyfumaroyl)-L-2,3-diaminopropionoic acid (Nva-FMDP), pointing toward its predominant role in their uptake mechanism. Altogether, the study provides an important template for future structure-function investigations of PTR transporters in Candida species. KEY POINTS: • Candida genome encodes for two distinct classes of PTR transporters. • Candida auris encodes for 3 PTR transporters with different specificities. • BNJ08_005124 in C. auris is involved in the uptake of Nikkomycin Z and Nva-FMDP., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Alzheimer's disease (AD) is a very complicated and multifactorial neurological disorder having limited therapeutic interventions illustrated by the impairment in memory and cognitive function. Several lines of confirmation are stoutly connected with mitochondrial function perturbation as a significant causative factor in AD, while the molecular mechanisms involved in AD pathogenesis are still poorly understood. Minocycline, a well-known antibiotic, has confirmed efficacy against mitochondrial defects and oxidative stress as a neuroprotective effect. In view of this property, we examined the remedial effect of minocycline on AD. To attain insight into the molecular machinery responsible for AD pathogenesis, we preferred the UAS/GAL4 scheme for the development of AD in flies that overexpress the Aβ42 protein in the brain of Drosophila . The warning signs like the declined lifespan, locomotion deficit and memory loss, impaired mitochondrial membrane potential, and increased caspase 3 expression with mitogen-associated protein kinases linked with AD pathogenesis were examined in the existence of minocycline. Minocycline halted the Aβ42-induced symptoms including behavioral changes and altered the mitochondrial membrane potential along with apoptotic factors' protein expression (JNK/p-JNK and caspase 3). Thus, the current study could be functional to find out the role of minocycline in human Aβ42-overexpressed transgenic AD flies., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Mycolic acids are the key constituents of mycobacterial cell wall, which protect the bacteria from antibiotic susceptibility, helping to subvert and escape from the host immune system. Thus, the enzymes involved in regulating and biosynthesis of mycolic acids can be explored as potential drug targets to kill Mycobacterium tuberculosis (Mtb). Herein, Kyoto Encyclopedia of Genes and Genomes is used to understand the fatty acid metabolism signaling pathway and integrative computational approach to identify the novel lead molecules against the mtFabH (β-ketoacyl-acyl carrier protein synthase III), the key regulatory enzyme of the mycolic acid pathway. The structure-based virtual screening of antimycobacterial compounds from ChEMBL library against mtFabH results in the selection of 10 lead molecules. Molecular binding and drug-likeness properties of lead molecules compared with mtFabH inhibitor suggest that only two compounds, ChEMBL414848 (C1) and ChEMBL363794 (C2), may be explored as potential lead molecules. However, the spatial stability and binding free energy estimation of thiolactomycin (TLM) and compounds C1 and C2 with mtFabH using molecular dynamics simulation, followed by molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) indicate the better activity of C2 (ΔG = -14.18 kcal/mol) as compared with TLM (ΔG = -9.21 kcal/mol) and C1 (ΔG = -13.50 kcal/mol). Thus, compound C1 may be explored as promising drug candidate for the structure-based drug designing of mtFabH inhibitors in the therapy of Mtb., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kumar, Srivastava, Mongre, Mishra, Kumar, Khatoon, Banerjee, Ashraf-Uz-Zaman, Singh, Lynn, Lee and Prakash.)

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Microhabitat factors associated with the habitat of barking deer (Muntiacus vaginalis) were examined and compared between summer and winter seasons. Habitat characteristics and preferred habitat were measured by locating direct and indirect signs. To quantify the habitat utilization of barking deer, each selected study site was sampled for floral diversity from 2015 to 2017. Quadrats were deployed along transect lines to determine seasonal distribution. Barking deer were not evenly distributed across vegetation types in the study area; they occurred more often in the broad-leaved forest than in Chir pine forest, at an elevational range of 550-850 m, in thick vegetation on steep slopes. The most preferred habitat included trees and shrubs with 30% and 69% cover, respectively. Barking deer avoided thicker tree cover, possibly as it hinders movement and escape from predators. No significant difference (χ2 = 6.37, df = 3, p = 0.19) in seasonal vegetation cover was recorded.

The introduction of heterostructures is a new approach in gas sensing due to their easy and quick transport of charges. Herein, facile hydrothermal and solid-state techniques are employed to synthesize an α-Fe 2 O 3 /Nb 2 O 5 heterostructure. The morphology, microstructure, crystallinity and surface composition of the synthesized heterostructures are investigated by scanning electron microscope, transmission electron microscope, x-ray diffraction, x-ray photoelectron spectroscopy and Brunauer-Emmett-Teller analyses. The successful fabrication of the heterostructures was achieved via the mutual incorporation of α-Fe 2 O 3 nanorods with Nb 2 O 5 interconnected nanoparticles (INPs). A sensor based on the α-Fe 2 O 3 (0.09)/Nb 2 O 5 heterostructure with a high surface area exhibited enhanced gas-sensing features, maintaining high selectivity and sensitivity, and a considerable recovery percentage towards ethanol gas. The sensing response of the α-Fe 2 O 3 (0.09)/Nb 2 O 5 heterostructure at lower operating temperature (160 °C) is around nine times higher than a pure Nb 2 O 5 (INP) sensor at 180 °C with the flow of 100 ppm ethanol gas. The sensors also show excellent selectivity, good long-term stability and a rapid response/recovery time (8s/2s, respectively) to ethanol. The superior electronic conductivity and upgraded sensitivity performance of gas sensors based on the α-Fe 2 O 3 (0.09)/Nb 2 O 5 heterostructure are attributed due to its unique structural features, high specific surface area and the synergic effect of the n-n heterojunction. The promising results demonstrate the potential application of the α-Fe 2 O 3 (0.09)/Nb 2 O 5 heterostructure as a good sensing material for the fabrication of ethanol sensors.

Northern red muntjac (Muntiacus vaginalis; "barking deer") is a shy and small-sized cervid mammal, limited to the outer Himalayan foothill forests in Pakistan. Habitat characteristics were measured by locating direct and indirect signs. To quantify habitat utilization of barking deer, 80 field surveys were conducted in the study area along transects. 1200 Quadrats at 50 m intervals were deployed along these transect lines to determine microhabitat factors associated with seasonal distribution. The food composition of the barking deer was determined through fecal droppings analysis by micro-histological technique. Forty-five fecal samples of barking deer were collected from the study area (Murree-Kotli Sattian-Kahuta National Pak); summer (28) and winter (17). The micro-histological analysis revealed that more plant species are available in its habitat during the summer season (27) as compared to winter (19). Due to browsing nature barking deer mostly feed on trees in both seasons. While shrubs are slightly higher in winters. In summer barking deer consumed 10 Trees, 6 Shrubs, 5 Herbs, and 6 kinds of grass species. Dominant tree species were Phyllanthus emblica and Acacia modesta. Dominant shrub species were Ziziphus nummularia and Justicia adhatoda. In winter barking deer consumed 8 Trees, 7 Shrubs, 3 Herbs, and 1 Grass. Dominant tree species were Bauhinia variegata and Acacia modesta while shrubs included Ziziphus nummularia and Carissa opaca., Competing Interests: The authors have declared that no competing interests exist.

The COVID-19 pandemic continues to spread throughout the world with an urgent need for a safe and protective vaccine to effectuate herd protection and control the spread of SARS-CoV-2. Here, we report the development of a SARS-CoV-2 subunit vaccine (NVX-CoV2373) from the full-length spike (S) protein that is stable in the prefusion conformation. NVX-CoV2373 S form 27.2-nm nanoparticles that are thermostable and bind with high affinity to the human angiotensin-converting enzyme 2 (hACE2) receptor. In mice, low-dose NVX-CoV2373 with saponin-based Matrix-M adjuvant elicit high titer anti-S IgG that blocks hACE2 receptor binding, neutralize virus, and protects against SARS-CoV-2 challenge with no evidence of vaccine-associated enhanced respiratory disease. NVX-CoV2373 also elicits multifunctional CD4 + and CD8 + T cells, CD4 + follicular helper T cells (Tfh), and antigen-specific germinal center (GC) B cells in the spleen. In baboons, low-dose levels of NVX-CoV2373 with Matrix-M was also highly immunogenic and elicited high titer anti-S antibodies and functional antibodies that block S-protein binding to hACE2 and neutralize virus infection and antigen-specific T cells. These results support the ongoing phase 1/2 clinical evaluation of the safety and immunogenicity of NVX-CoV2373 with Matrix-M (NCT04368988).

In this work, we report the spontaneous formation of NiO nanoparticles-decorated onto smooth SnO 2 nanofibers, which is an inexpensive and scalable method for yielding a high composite surface area via a simple two-step synthesis process based on electrospinning and the hydrothermal method. A Nickel Oxide proton-conducting electrolyte is deposited homogeneously over a large surface area in a transparent solution, mixed and decorated onto Tin dioxide nanofibers, as evidenced by cross sectional imaging of the electrospun nanofibers. The composite based on nanoparticle-decorated fibers enlarges the surface area of the exposed electrolyte, which fundamentally improves the overall gas sensing performance. The crystal structure, morphology, and physio-chemical surface state of the NiO/SnO 2 -based specimen are comprehensively examined using XRD, SEM, TEM, HRTEM, EDX, and photoelectron (XPS) spectroscopy. The composite based on NiO/SnO 2 nanoparticle-decorated fibers exhibits an optimistic mesoporous nature with a huge specific area, which is key for superior gas sensors. The result reveals that NiO/SnO 2 nanoparticle-decorated fibers with an average size of 180-260 nm in diameter, where the average length of fibers was about 1.5 μm. The composite-based heterojunction of NiO/SnO 2 nanoparticle-decorated fibers enhances the adsorption of oxygen molecules, which show fast response, good selectivity and quick recovery speed against ethanol gas at an optimal temperature of about 160 °C. The maximum sensitivity response of the sensor-based composite NiO/SnO 2 nanoparticle-decorated fibers was 23.87 in respect of 100 ppm ethanol gas at a low temperature of 160 °C; this is approximately about 7.2 times superior to that of pure SnO 2 nanofibers. The superior gas sensing capabilities of a composite based on NiO/SnO 2 nanoparticle-decorated fibers may be attributable to the enhanced catalytic effect of the small sized NiO nanoparticles on smooth SnO 2 nanofibers, together with the p/n heterojunction effects between NiO and SnO 2 heterostructures.

A novel composite based on α-Bi 2 Mo 3 O 12 /Co 3 O 4 nanotube-decorated particles was successfully synthesized using a highly efficient and facile two step system using electrospinning and hydrothermal techniques. The small size Co 3 O 4 nanoparticles were uniformly and hydrothermally developed on the electrospun α-Bi 2 Mo 3 O 12 nanotubes. The pure α-Bi 2 Mo 3 O 12 nanofibers and composite based on α-Bi 2 Mo 3 O 12 /Co 3 O 4 were examined using X-ray powder diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), transmission electron microscopy (TEM), high resolution transmission electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS) and Brunauer-Emmett-Teller (BET) analyses. From the BET measurements, the composite based on α-Bi 2 Mo 3 O 12 /Co 3 O 4 exhibits a large specific surface area of 54 m 2 g -1 with mesopore diameter ranges of 2-10 nm, which is mainly attributed to the remarkable and dominant enhancement in gas sensing as compared to that of the pure α-Bi 2 Mo 3 O 12 nanofibers (38 m 2 g -1 ) and Co 3 O 4 nanoparticles (32 m 2 g -1 ), respectively. In this work, the novel composite based on α-Bi 2 Mo 3 O 12 /Co 3 O 4 presented a high sensitivity of 30.25 with a quick response/recovery speed towards 100 ppm ethanol at an optimal working temperature of 170 °C, as compared to the pure α-Bi 2 Mo 3 O 12 nanofibers and Co 3 O 4 nanoparticles, which display a sensitivity of 13.10 and 2.99 at an optimal working temperature of 220 °C and 280 °C. The sensing performance of the composite based on the α-Bi 2 Mo 3 O 12 /Co 3 O 4 sensor exhibits a superior sensing performance towards ethanol, which might be owed to the enormous number of superficial oxygen species, the small size catalytic effect of the Co 3 O 4 nanoparticles and the interfacial effect formed between the n-type α-Bi 2 Mo 3 O 12 and p-type Co 3 O 4 leading to a high charge carrier concentration. This is a novel investigation of a composite based on an α-Bi 2 Mo 3 O 12 /Co 3 O 4 sensor in the gas sensing era, which might be of vital importance in applications in the advanced gas sensing field., Competing Interests: We do not have any competing financial interests. All the work is based on an interest in Science and Technology., (This journal is © The Royal Society of Chemistry.)