Restoration of the soil fertility under Cr(VI) and artificial drought condition by the utilization of plant growth-promoting Bacillus spp. SSAU2.

The study explores the potential of an indigenous halo-tolerant microbe identified as Bacillus spp. SSAU-2 in enhancing soil fertility and promoting plant growth for sustainable agricultural practices under the influence of multiple abiotic stresses such as Cr(VI), high salinity, and artificial drought condition. The study investigated various factors influencing IAA synthesis by SSAU-2, such as pH (5 to 11), salinity (10 to 50 g/L), tryptophan concentration (0.5 to 1%), carbon (mannitol mand lactose), and nitrogen sources (peptone and tryptone). The highest IAA concentration was observed at pH 10 (1.695 mg/ml) and pH 11 (0.782 mg/ml). IAA synthesis was optimized at a salinity level of 30 g/l, with lower and higher salinity levels resulting in decreased IAA concentrations. Notably, the presence of mannitol and lactose significantly augmented IAA synthesis, while glucose and sucrose had inhibitory effects. Furthermore, peptone and tryptone played a pivotal role in enhancing IAA synthesis, while ammonium chloride exerted an inhibitory influence. SSAU-2 showed a diverse array of capabilities, including the synthesis of gibberellins, extracellular polymeric substances, siderophores, and hydrogen cyanide along with nitrogen fixation and ammonia production. The microbe could efficiently tolerate 45% PEG-6000 concentration and effectively produce IAA in 15% PEG concentration. It could also tolerate high concentration of Cr(VI) and synthesize IAA even in 50 ppm Cr(VI). The findings of this study provide valuable insights into harnessing the potential of indigenous microorganisms to promote plant growth, enhance soil fertility, and establish sustainable agricultural practices essential for restoring the health of ecosystems.

Regnase-1 D141N mutation induces CD4+ T cell-mediated lung granuloma formation via upregulation of Pim2.

Regnase-1 is an RNase that plays a critical role in negatively regulating immune responses by destabilizing inflammatory mRNAs. Dysfunction of Regnase-1 can be a major cause of various inflammatory diseases with tissue injury and immune cell infiltration into organs. This study focuses on the role of RNase activity of Regnase-1 in developing inflammatory diseases. We have constructed mice with a single point mutation at the catalytic center of Regnase-1 RNase domain, which lacks endonuclease activity. D141N mutant mice demonstrated systemic inflammation, immune cell infiltration into various organs and progressive development of lung granuloma. CD4+ T cells, mainly affected by this mutation, upregulated mTORC1 pathway and facilitated the autoimmune trait in D141N mutation. Moreover, serine/threonine kinase Pim2 contributed to lung inflammation in this mutation. Inhibition of Pim2 kinase activity ameliorated granulomatous inflammation, immune cell infiltration and proliferation in the lungs. Additionally, Pim2 inhibition reduced the expression of adhesion molecules on CD4+ T cells, suggesting a role for Pim2 in facilitating leukocyte adhesion and migration to inflamed tissues. Our findings provide new insights into the role of Regnase-1 RNase activity in controlling immune function and underscore the therapeutic relevance of targeting Pim2 to modulate abnormal immune responses.

Deletion of the mRNA endonuclease Regnase-1 promotes NK cell anti-tumor activity via OCT2-dependent transcription of Ifng.

Limited infiltration and activity of natural killer (NK) and T cells within the tumor microenvironment (TME) correlate with poor immunotherapy responses. Here, we examined the role of the endonuclease Regnase-1 on NK cell anti-tumor activity. NK cell-specific deletion of Regnase-1 (Reg1ΔNK) augmented cytolytic activity and interferon-gamma (IFN-γ) production in vitro and increased intra-tumoral accumulation of Reg1ΔNK-NK cells in vivo, reducing tumor growth dependent on IFN-γ. Transcriptional changes in Reg1ΔNK-NK cells included elevated IFN-γ expression, cytolytic effectors, and the chemokine receptor CXCR6. IFN-γ induced expression of the CXCR6 ligand CXCL16 on myeloid cells, promoting further recruitment of Reg1ΔNK-NK cells. Mechanistically, Regnase-1 deletion increased its targets, the transcriptional regulators OCT2 and IκBζ, following interleukin (IL)-12 and IL-18 stimulation, and the resulting OCT2-IκBζ-NF-κB complex induced Ifng transcription. Silencing Regnase-1 in human NK cells increased the expression of IFNG and POU2F2. Our findings highlight NK cell dysfunction in the TME and propose that targeting Regnase-1 could augment active NK cell persistence for cancer immunotherapy.

Skin Cancer Image Segmentation Based on Midpoint Analysis Approach.

Skin cancer affects people of all ages and is a common disease. The death toll from skin cancer rises with a late diagnosis. An automated mechanism for early-stage skin cancer detection is required to diminish the mortality rate. Visual examination with scanning or imaging screening is a common mechanism for detecting this disease, but due to its similarity to other diseases, this mechanism shows the least accuracy. This article introduces an innovative segmentation mechanism that operates on the ISIC dataset to divide skin images into critical and non-critical sections. The main objective of the research is to segment lesions from dermoscopic skin images. The suggested framework is completed in two steps. The first step is to pre-process the image; for this, we have applied a bottom hat filter for hair removal and image enhancement by applying DCT and color coefficient. In the next phase, a background subtraction method with midpoint analysis is applied for segmentation to extract the region of interest and achieves an accuracy of 95.30%. The ground truth for the validation of segmentation is accomplished by comparing the segmented images with validation data provided with the ISIC dataset.

Predictors of apical periodontitis in root canal treated teeth from an adult Nepalese subpopulation: a cross-sectional study.

BACKGROUND: Endodontic literature search revealed that no study has been conducted to evaluate the prevalence of apical periodontitis (AP) in root canal treated teeth from an adult Nepalese population of Madhesh Province. Consequently, little is known about the extent and risk factors associated with it. This study aimed to determine AP prevalence in root canal treated teeth from an adult Nepalese subpopulation and to analyze the related risk factors including age, sex, tooth type, type of coronal restoration and quality of root canal treatment and coronal restoration as predictors of AP. METHODS: Digital panoramic radiographs were evaluated. Periapical status of 300 root canal-treated teeth was scored by using the periapical index. The quality of root canal treatment and coronal restorations were categorized as adequate or inadequate through radiographic and clinical evaluation. The data were analyzed using univariate and multivariate logistic regression models. RESULTS: Prevalence of AP in the present study was 31.7%. In 45.7% of the treated teeth, quality of root canal treatment was adequate whereas 46% of the cases had adequate coronal restorations. Multivariate logistic regression analysis revealed statistically significant associations and remarkably increased risk for AP in teeth with inadequate root canal treatment (odds ratio [OR] = 7.92; 95% CI: 3.96-15.82; p < 0.001) whereas lower risk for AP was found in females (OR = 0.51; 95% CI: 0.28-0.90; p = 0.021) and in teeth restored with crown (OR = 0.22; 95% CI: 0.09-0.51; p < 0.001) and filling (OR = 0.18; 95% CI: 0.08-0.42; p < 0.001). Quality of coronal restoration, tooth type and age of the patient were not found to be the predictors of AP. CONCLUSIONS: Within the limits of this study, a high prevalence of AP and poor overall quality of root canal treatment and coronal restoration was found in the subpopulation studied. Quality of root canal treatment, type of coronal restoration and sex of the patient are significant predictors of possible AP development in root canal treated teeth. Substantial efforts are needed to improve the endodontic treatment standards.

CGRP sensory neurons promote tissue healing via neutrophils and macrophages.

The immune system has a critical role in orchestrating tissue healing. As a result, regenerative strategies that control immune components have proved effective1,2. This is particularly relevant when immune dysregulation that results from conditions such as diabetes or advanced age impairs tissue healing following injury2,3. Nociceptive sensory neurons have a crucial role as immunoregulators and exert both protective and harmful effects depending on the context4-12. However, how neuro-immune interactions affect tissue repair and regeneration following acute injury is unclear. Here we show that ablation of the NaV1.8 nociceptor impairs skin wound repair and muscle regeneration after acute tissue injury. Nociceptor endings grow into injured skin and muscle tissues and signal to immune cells through the neuropeptide calcitonin gene-related peptide (CGRP) during the healing process. CGRP acts via receptor activity-modifying protein 1 (RAMP1) on neutrophils, monocytes and macrophages to inhibit recruitment, accelerate death, enhance efferocytosis and polarize macrophages towards a pro-repair phenotype. The effects of CGRP on neutrophils and macrophages are mediated via thrombospondin-1 release and its subsequent autocrine and/or paracrine effects. In mice without nociceptors and diabetic mice with peripheral neuropathies, delivery of an engineered version of CGRP accelerated wound healing and promoted muscle regeneration. Harnessing neuro-immune interactions has potential to treat non-healing tissues in which dysregulated neuro-immune interactions impair tissue healing.

Neonatal nephrotic syndrome: all is not gloomy.

Congenital nephrotic syndrome (CNS) is a rare clinical syndrome with a constellation of proteinuria, hypoalbuminaemia and oedema, presenting within 3 months of birth. We present a rare case of neonatal nephrotic syndrome with a probable sepsis induced aetiology. The neonate was referred at day of life 15 with Klebsiella pneumonia sepsis and anasarca. On investigation, the patient had nephrotic range proteinuria, hypoalbuminaemia, generalised anasarca and ascites. The neonate was started on broad-spectrum antibiotics and furosemide. Genetic and other secondary causes of CNS were ruled out. With supportive management and resolution of sepsis, the neonate improved. This case highlights the rare cause of sepsis-induced nephrotic syndrome (NS), which required only supportive treatment without the need for aggressive management of CNS.

Double BCG vaccination in a neonate: implications, management and prevention.

Tuberculosis is a common cause of morbidity and mortality especially in low-income and middle-income countries like India. BCG vaccination is recommended for all neonates after birth in areas with a high tuberculosis disease burden. Here, we describe a case where a neonate received two doses of the BCG (Chennai strain) vaccine within a span of 4 days after birth due to a vaccination error. Parents were informed about the event. The infant was managed conservatively and followed up till 12 months of life for any possible complication. There were no serious adverse effects apart from the localised reaction and a double scar on the left arm. Measures to avoid any such error in the future and the need for reporting medication error has been highlighted. Parental concerns are frequent in such scenarios and should be actively addressed.

Bio Prospecting of Endophytes and PGPRs in Artemisinin Production for the Socio-economic Advancement.

The growing demand for Artemisia annua plants in healthcare, food, and pharmaceutical industries has led to increased cultivation efforts to extract a vital compound, Artemisinin. The efficacy of Artemisinin as a potent drug against malaria disease is well established but its limited natural abundance. However, the common practice of using chemical fertilizers for maximum yield has adverse effects on plant growth, development, and the quality of phytochemicals. To address these issues, the review discusses the alternative approach of harnessing beneficial rhizosphere microbiota, particularly plant growth-promoting rhizobacteria (PGPR). Microbes hold substantial biotechnological potential for augmenting medicinal plant production, offering an environmentally friendly and cost-effective means to enhance medicinal plant production. This review article aims to identify a suitable endophytic population capable of enabling Artemisia sp. to thrive amidst abiotic stress while simultaneously enhancing Artemisinin production, thereby broadening its availability to a larger population. Furthermore, by subjecting endophytes to diverse combinations of harsh conditions, this review sheds light on the modulation of essential artemisinin biosynthesis pathway genes, both up regulated and down regulated. The collective findings suggest that through the in vitro engineering of endophytic communities and their in vivo application to Artemisia plants cultivated in tribal population fields, artemisinin production can be significantly augmented. The overall aim of this review to explore the potential of harnessing microbial communities, their functions, and services to enhance the cultivation of medicinal plants. It outlines a promising path toward bolstering artemisinin production, which holds immense promise in the fight against malaria.

Electrochemical, surface morphological and computational evaluation on carbohydrazide Schiff bases as corrosion inhibitor for mild steel in acidic medium.

Anticorrosion and adsorption behaviour of synthesized carbohydrazide Schiff bases, namely (Z)-N'-(4-hydroxy-3-methoxybenzylidene)-6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carbohydrazide(MBTC) and (Z)-N'-(3,4-dichlorobenzylidene)-6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carbohydrazide (CBTC) was examined for mild steel (MS) in 15% HCl medium. The corrosion inhibition study was performed by using gravimetric, thermodynamic, electrochemical and theoretical studies including density functional theory (DFT), molecular dynamic simulation (MDS) and Monte Carlo simulations (MCS). The outcomes in terms of corrosion inhibition efficiency using electrochemical impedance spectroscopy (EIS) method at 303 K and 150 ppm concentration were 96.75% for MBTC and 95.14% for CBTC. Both inhibitors adsorbed on the MS surface through physical as well as chemical adsorption and followed the Langmuir isotherm. The mixed-type nature of both inhibitors was identified by polarization results. Surface analysis was done using FESEM, EDX, AFM and XPS studies and results showed that a protective layer of inhibitor molecules was developed over the surface of MS. The results of DFT, MCS and MDS are in accordance with experimental results obtained by weight loss and electrochemical methods.

Prevalence of Obesity in Newly Onset Diabetes Mellitus and Its Relationship with Uric Acid: An Indian Cross-Sectional Study.

Introduction: Prevalence of obesity is high in diabetes mellitus (DM) and is associated with hyperuricemia (HU), hypertension, metabolic syndrome, cardiovascular disease and dyslipidemia. In obesity, elevated serum uric acid (SUA) has been shown to be associated in many studies from different countries, but data from India are lacking. The aim of the present study is to know the prevalence of obesity and to know the relationship between obesity and SUA in newly onset DM. Methods: In this cross-sectional study from India, 402 consecutive newly onset diabetic patients (male: 284; female: 118) were enrolled. All patients were grouped into four based on BMI (body mass index): underweight (<18.5 kg/m2), normal weight (18.5-23 kg/m2), overweight (>23-27.5 kg/m2), and obese (>27.5 kg/m2). All participants were grouped into four quartiles based on SUA (Q1: <4.23; Q2: ≥4.24-5.19; Q3: ≥5.20-6.16; Q4: >6.16). Results: The mean age, BMI and SUA of the participants were 46.20±0.52 years, 26.35±0.21 kg/m2 and 5.24±0.007 mg/dl, respectively. Overall prevalence of generalized obesity, central obesity and hyperuricemia (HU) were 35.07%, 85.82% and 13.43%, respectively. The prevalence of generalized obesity increased across the SUA quartile. A multinomial logistic regression analysis showed that serum uric acid level was independently associated with generalized obesity (p<0.001). Conclusion: This first report from India shows a significant positive association between SUA and generalized obesity among newly onset DM. Therefore, routine estimation of SUA is recommended in newly onset DM to prevent and treat HU and its related complications.

Lesbian longings and the question of a queer repertoire in The "Other" Love Story.

In recent years, there has been an emerging critical discourse in South Asia that examines the changing contours of representational politics that could, in turn, be strategically mobilized to introduce an alternative idiom of same-sex love within a standard template of heterosexual storytelling. This has been complemented by an evaluation of alternative modes of sexual politics that need not necessarily conform to Western labels or paradigms of queer identities. Taking its cue from such discursive readings, this article demonstrates how Roopa Rao's web series, The "Other" Love Story (2016), revisits some of the dominant tropes, practices, and narrative conventions of the Hindi films, released in the 1990s, to create a counter-archive for the lesbian subject who, for the most part, was conspicuous by her very absence in the popular figurations of that period in South Asia. There is a perceptible strand of lingering nostalgia and artistic homage that undergirds such an experimental project that nevertheless also becomes a disruptive site for articulating an oppositional esthetics of romance. The subtlety and restraint of such a nuanced portrayal of dissident desires and queer intimacies thus not only resist the easy appropriations that women in the subcontinent are routinely subjected to (as veritable repositories of tradition and national identity) but also retrospectively reclaim a voice for an otherwise historically silenced discourse of sexuality for the masses.

The Deadly Duo of Hypertension and Diabetes in India: Further Affirmation from a New Epidemiological Study.

We read with great interest the article "the deadly duo of hypertension and diabetes in India: further affirmation from a new epidemiological study" by Metri et al.1 They rightly pointed out that the prevalence of hypertension in Indian patients with type 2 diabetes patients is high and therefore early screening and management of hypertension should be included in the treatment of patients with type 2 diabetes. We wish to share our study findings on the prevalence of hypertension in newly onset diabetes mellitus (DM). We find that the prevalence of hypertension in all males and females with DM was 44.59, 44.34, and 45.16%, respectively.2.

Immuno-localization of definitive hematopoietic stem cells in the vascular niche of mouse fetal liver.

Understanding the murine fetal liver (FL) hematopoietic microenvironment, which promotes HSC proliferation, warrants identifying innate relationships between stem cells and the niche. An inclusive study of these cell associations remains elusive. Here, we optimized a protocol to immunolabel HSCs alongside the FL vasculature, a promising niche component. We provide a comprehensive plan from tissue processing, immunohistochemistry, and confocal microscopy, to three-dimensional distance analyses between HSCs and vasculature. This technique can be adapted for achieving congruous outcomes for other cell types. For complete details on the use and execution of this protocol, please refer to Biswas et al. (2020).

Nitrate contamination in water resources, human health risks and its remediation through adsorption: a focused review.

The level of nitrate in water has been increasing considerably all around the world due to vast application of inorganic nitrogen fertiliser and animal manure. Because of nitrate's high solubility in water, human beings are getting exposed to it mainly through various routes including water, food etc. Various regulations have been set for nitrate (45-50 mgNO3-/L) in drinking water to protect health of the infants from the methemoglobinemia, birth defects, thyroid disease, risk of specific cancers, i.e. colorectal, breast and bladder cancer caused due to nitrate poisoning. Different methods like ion exchange, adsorption, biological denitrification etc. have the ability to eliminate the nitrate from the aqueous medium. However, adsorption process got preference over the other approaches because of its simple design and satisfactory results especially with surface modified adsorbents or with mineral-based adsorbents. Different types of adsorbents have been used for this purpose; however, adsorbents derived from the biomass wastes have great adsorption capacities for nitrate such as tea waste-based adsorbents (136.43 mg/g), carbon nanotube (142.86 mg/g), chitosan beads (104 mg/g) and cetyltrimethylammonium bromide modified rice husk (278 mg/g). Therefore, a thorough literature survey has been carried out to formulate this review paper to understand various sources of nitrate pollution, route of exposure to the human beings, ill effects along with discussing the key developments as well as the new advancements reported in procuring low-cost efficient adsorbents for water purification.

Prevalence of Hyperuricemia and the Relationship Between Serum Uric Acid and Hypertension in New Onset Diabetic Patients: A Cross-Sectional Indian Study.

Objective: Prevalence of hyperuricemia (HU) is increasing and it is associated with hypertension, metabolic syndrome, diabetes mellitus (DM), obesity, chronic kidney disease, gout and cardiovascular disease. Elevated level of serum uric acid (SUA) has been shown to be associated with hypertension and diabetes in many countries but there is lack of evidence from India. The aim of this study is to know the prevalence of HU and to know the relationship between SUA and hypertension in newly onset DM. Methods: This is a cross-sectional study from a tertiary center. A total of 305 (males: 212; females: 93) newly diagnosed diabetic patients were enrolled. All patients were categorized as normotensive (<140/90) and hypertensive (≥140/90) based on ADA criteria. Based on SUA level participants were grouped into 3 tertile (T1: <4.52; T2: 4.52-5.64; T3: >5.64 mg/dl). Results: The mean age, systolic blood pressure (SBP) and diastolic blood pressure (DBP) of the patients were 46.76 ±0.61 years, 130.6±1.06 mmHg and 84.11±0.63 mmHg, respectively. The mean level of SUA was 5.14±0.073 mg/dl and level was significantly higher in males compared with females (P <0.000). Overall prevalence of HU and hypertension was 12.13% and 44.59%, respectively. There was an increase in the prevalence of hypertension across the SUA tertile. SBP and DBP significantly increased across the SUA tertile (P <0.014 and <0.001, respectively). A multiple logistic regression analysis revealed that SUA tertile was independently associated with presence of hypertension (P <0.01). Conclusion: This first report on the population of the eastern part of India indicates a significant positive relationship between SUA and hypertension among the newly onset Indian diabetic patients. Therefore, routine measurement of SUA is recommended in newly onset hypertensive diabetic patients to prevent HU and its related complications.

Management of Glucocorticoid-Induced Hyperglycemia.

Glucocorticoids are potent immunosuppressive and anti-inflammatory drugs used for various systemic and localized conditions. The use of glucocorticoids needs to be weighed against their adverse effect of aggravating hyperglycemia in persons with diabetes mellitus, unmask undiagnosed diabetes mellitus, or precipitate glucocorticoid-induced diabetes mellitus appearance. Hyperglycemia is associated with poor clinical outcomes, including infection, disability after hospital discharge, prolonged hospital stay, and death. Furthermore, clear guidelines for managing glucocorticoid-induced hyperglycemia are lacking. Therefore, this consensus document aims to develop guidance on the management of glucocorticoid-induced hyperglycemia. Twenty expert endocrinologists, in a virtual meeting, discussed the evidence and practical experience of real-life management of glucocorticoid-induced hyperglycemia. The expert group concluded that we should be proactive in terms of diagnosis, management, and post-steroid care. Since every patient has different severity of underlying disease, clinical stratification would help understand patient profiles and determine the treatment course. Patients at home with pre-existing diabetes who are already on oral or injectable therapy can continue the same as long as they are clinically stable and eating adequately. However, depending on the degree of hyperglycemia, modification of doses may be required. Initiating basal bolus with correction regimen is recommended for patients in non-intensive care unit settings. For patients in intensive care unit, variable rate intravenous insulin infusion could be temporarily used, but under supervision of diabetes inpatient team, and patients can be transitioned to subcutaneous insulin once stable baseline assessment and continual evaluation are crucial for day-to-day decisions concerning insulin doses. Glycemic variability should be carefully monitored, and interventions to treat patients should also aim at achieving and maintaining euglycemia. Rational use of glucose-lowering drugs is recommended and treatment regimen should ensure maximum safety for both patient and provider. Glucovigilance is required as the steroids taper during transition, and insulin dosage should be reduced subsequently. Increased clinical and economic burden resulting from corticosteroid-related adverse events highlights the need for effective management. Therefore, these recommendations would help successfully manage GC-induced hyperglycemia and judiciously allocate resources.

Effect of Different Molecular Weights of Chitosan on Formulation and Evaluation of Allopurinol-Loaded Nanoparticles for Kidney Targeting and in Management of Hyperuricemic Nephrolithiasis.

Present research study was conducted to formulate kidney-targeted allopurinol (AO)-loaded chitosan nanoparticles (ANPs) for management of hyperuricemic related nephrolithiasis. Different molecular weights of chitosan were used for fabricating ANP formulation by adopting modified ionotropic gelation method. The prepared batches were than evaluated for particle size analysis, entrapment efficiency, transmission electron microscopy, X-ray diffraction, Differential Scanning Calorimetry, in vitro release and in vivo animal study. The in vivo study depicted that post 2 h of administration of different formulations and pure drug; ANPs prepared from low molecular weight chitosan showed maximum concentration of AO in kidney signifying successful kidney targeting of drug (25.92 fold) whereas no or very less amount of AO was seen in other animal groups. Effectiveness (p < 0.01) of formulation in management of hyperuricemia-associated nephrolithiasis was also evaluated via estimation of urine pH and serum and urine uric acid levels of mice. Further histological study was also performed on kidney samples which again affirmed these results. Present investigation demonstrated that ANPs prepared from low MW chitosan depicted maximum kidney-targeting ability that might be due to its specific uptake by the kidneys as well as its higher solubility than other two polymers, which results in enhanced release rate from the formulation and also offers an efficient strategy for the management of hyperuricemic nephrolithiasis.