Polygenic Risk Score Assessment for Coronary Artery Disease in Asian Indians.

We evaluated the performance of various polygenic risk score (PRS) models derived from European (EU), South Asian (SA), and Punjabi Asian Indians (AI) studies on 13,974 subjects from AI ancestry. While all models successfully predicted Coronary artery disease (CAD) risk, the AI, SA, and EU + AI were superior predictors and more transportable than the EU model; the predictive performance in training and test sets was 18% and 22% higher in AI and EU + AI models, respectively than in EU. Comparing individuals with extreme PRS quartiles, the AI and EU + AI captured individuals with high CAD risk showed 2.6 to 4.6 times higher efficiency than the EU. Interestingly, including the clinical risk score did not significantly change the performance of any genetic model. The enrichment of diversity variants in EU PRS improves risk prediction and transportability. Establishing population-specific normative and risk factors and inclusion into genetic models would refine the risk stratification and improve the clinical utility of CAD PRS.

Stilbenes: a journey from folklore to pharmaceutical innovation.

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

Mastalgia - The Burden Beneath.

Objective: Mastalgia is the most common breast-related complaint. A multitude of hormonal changes and lifestyle associated factors have been implicated in its causation. A long list of treatment modalities have been tried with varying success rates. To identify the most common risk factors and the most effective management strategies for mastalgia in our clinic population. Materials and Methods: A total of 100 women between 18-65 years of age presenting to the breast clinic with mastalgia were followed throughout their course of diagnosis and management. Stepwise treatment was provided, starting with reassurance and breast support and progressing to include pharmacological measures, when necessary. The risk factors and outcomes of treatment were analysed. Results: The majority (66%) were aged 25-47 years and the left breast was found to be most frequently involved. Involvement of the upper outer quadrant was significantly more common. Lump/nodularity was the most prevalent risk factor. Most patients showed a positive response to non-steroid anti-inflammatories (NSAIDs) in addition to reassurance, breast support and dietary changes. Conclusion: A detailed history and clinical examination helps to identify the risk factors and the best approach for the management of mastalgia. Educating women regarding breast self-examination at regular intervals helps in early presentation and diagnosis of the underlying condition. Reassurance, breast support and lifestyle changes are the first line treatment and have good results in a significant number of patients. In our practice topical and oral NSAIDs, evening primrose oil and vitamin E were frequently used as additional treatments to non-pharmacological methods.

Scaffold hopping based designing of selective ALDH1A1 inhibitors to overcome cyclophosphamide resistance: synthesis and biological evaluation.

Aldehyde dehydrogenase 1A1 (ALDH1A1) is an isoenzyme that catalyzes the conversion of aldehydes to acids. However, the overexpression of ALDH1A1 in a variety of malignancies is the major cause of resistance to an anti-cancer drug, cyclophosphamide (CP). CP is a prodrug that is initially converted into 4-hydroxycyclophosphamide and its tautomer aldophosphamide, in the liver. These compounds permeate into the cell and are converted as active metabolites, i.e., phosphoramide mustard (PM), through spontaneous beta-elimination. On the other hand, the conversion of CP to PM is diverted at the level of aldophosphamide by converting it into inactive carboxyphosphamide using ALDH1A1, which ultimately leads to high drug inactivation and CP resistance. Hence, in combination with our earlier work on the target of resistance, i.e., ALDH1A1, we hereby report selective ALDH1A1 inhibitors. Herein, we selected a lead molecule from our previous virtual screening and implemented scaffold hopping analysis to identify a novel scaffold that can act as an ALDH1A1 inhibitor. This results in the identification of various novel scaffolds. Among these, on the basis of synthetic feasibility, the benzimidazole scaffold was selected for the design of novel ALDH1A1 inhibitors, followed by machine learning-assisted structure-based virtual screening. Finally, the five best compounds were selected and synthesized. All synthesized compounds were evaluated using in vitro enzymatic assay against ALDH1A1, ALDH2, and ALDH3A1. The results disclosed that three molecules A1, A2, and A3 showed significant selective ALDH1A1 inhibitory potential with an IC50 value of 0.32 µM, 0.55 µM, and 1.63 µM, respectively, and none of the compounds exhibits potency towards the other two ALDH isoforms i.e. ALDH2 and ALDH3A1. Besides, the potent compounds (A1, A2, and A3) have been tested for in vitro cell line assay in combination with mafosfamide (analogue of CP) on two cell lines i.e. A549 and MIA-PaCa-2. All three compounds show significant potency to reverse mafosfamide resistance by inhibiting ALDH1A1 against these cell lines.

Baseline and oxidatively damaged DNA in end-stage renal disease patients on varied hemodialysis regimens: a comet assay assessment.

Global estimates exhibit that one million people have end-stage renal disease, a disease-state characterized by irreversible loss of kidney structure and function, thus necessitating renal replacement therapy. The disease-state, oxidative stress, inflammatory responses, as well as the treatment procedure can have damaging effects on the genetic material. Therefore, the present study was carried out to investigate DNA damage (basal and oxidative) using the comet assay in peripheral blood leukocytes of patients (n = 200) with stage V Chronic Kidney Disease (on dialysis and those recommended but yet to initiate dialysis) and compare it to that in controls (n = 210). Basal DNA damage was significantly elevated (1.13x, p ≤ 0.001) in patients (46.23 ± 0.58% DNA in tail) compared to controls (40.85 ± 0.61% DNA in tail). Oxidative DNA damage was also significantly (p ≤ 0.001) higher in patients (9.18 ± 0.49 vs. 2.59 ± 0.19% tail DNA) compared to controls. Twice-a-week dialysis regimen patients had significantly elevated % tail DNA and Damage Index compared to the non-dialyzed and to the once-a-week dialysis group implying dialysis- induced mechanical stress and blood-dialyzer membrane interactions as probable contributors to elevated DNA damage. The present study with a statistically significant power implies higher disease-associated as well as maintenance therapy (hemodialysis)-induced basal and oxidatively damaged DNA, which if not repaired has the potential to initiate carcinogenesis. These findings mark the need for improvement and development of interventional therapies for delaying disease progression and associated co-morbidities so as to improve life expectancy of patients with kidney disease.

Plant growth-promoting endophyte Nigrospora oryzae mitigates abiotic stress in rice (Oryza sativa L.).

Climate change has severely impacted crop productivity. Nascent technologies, such as employing endophytic fungi to induce crop adaptogenic changes, are being explored. In this study, 62 isolates of fungi existing as endophytes were recovered from different parts of a drought-resistant rice variety and screened for salinity and drought tolerance. Nigrospora oryzae #2OSTUR9a exhibited in vitro antioxidant potential, indole acetic acid (351.01 ± 7.11 µg/mL), phosphate solubilisation (PI 1.115 ± 0.02), siderophore (72.57% ± 0.19%) and 1-aminocyclopropane-1-carboxylate deaminase production (305.36 ± 0.80 nmol α-ketobutyrate/mg/h). To the best of our knowledge, this is the first report on salinity and drought stress mitigation in rice plants by endophytic N. oryzae. In treated plants under salinity stress, the relative water, chlorophyll, phenolic and osmolyte content increased by 48.39%, 30.94%, 25.32% and 43.67%, respectively, compared with their respective controls. A similar trend was observed under drought stress, where the above parameters increased by 50.31%, 39.47%, 32.95% and 50.42%, respectively. Additionally, the antioxidant status of the treated plants was much higher because of the enhanced antioxidant enzymes and reduced lipid peroxidation. Our findings indicate the ability of N. oryzae to effectively mitigate the impact of stress, thereby enabling the rice plant to sustain stress conditions.

Promising drought and salinity tolerance features of Nigrospora species existing as endophytes in Oryza sativa.

In this study, we report the discovery of novel Nigrospora species isolated from the extensively cultivated PUSA 44 rice variety in Punjab, India. Out of the 120 isolates examined, 6.6% and 5% isolates exhibited tolerance to high salinity and drought stress. Isolates 6OSFR2e and 7OSFS3a exhibited the highest indole acetic acid and gibberellic acid production, with 268.32 ± 08.10 and 25.72 ± 0.04 µg/mL. Additionally, isolates 7OSFS3a, 6OSFR2e and 6OSFL4c had highest antioxidant potential with IC50 345.45 ± 11.66, 391.58 ± 10.66, and 474.529 ± 11.08 µg/mL. The isolates 6OSFR2e and 6OSFL4c also exhibited phosphate solubilisation with a PI of 1.06 ± 0.00 and 1.04 ± 0.02. The highest cellulase and laccase production with EI 1.24 ± 0.00 and 1.16 ± 0.00 was observed by isolates 6OSFR2e and 6OSFL4c. Promising results were observed in the case of ammonia production. The isolates belonged to the same phylum, Ascomycota and were identified as Nigrospora zimmermanii (6OSFR2e) and Nigrospora oryzae (7OSFS3a), and Nigrospora sphaerica (6OSFL4c) using morpho-taxonomic and molecular identification. The present study provides a critical insight into the characteristics of these Nigrospora species, which could be used to develop a bio-consortium for the rejuvenation of PUSA-44 cultivation. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03679-9.

Raloxifene and bazedoxifene as selective ALDH1A1 inhibitors to ameliorate cyclophosphamide resistance: A drug repurposing approach.

Cyclophosphamide (CP) is one of the most widely used anticancer drugs for various malignancies. However, its long-term use leads to ALDH1A1-mediated inactivation and subsequent resistance which necessitates the development of potential ALDH1A1 inhibitors. Currently, ALDH1A1 inhibitors from different chemical classes have been reported, but these failed to reach the market due to safety and efficacy problems. Developing a new treatment from the ground requires a huge amount of time, effort, and money, therefore it is worthwhile to improve CP efficacy by proposing better adjuvants as ALDH1A1 inhibitors. Herein, the database constituting the FDA-approved drugs with well-established safety and toxicity profiles was screened through already reported machine learning models by our research group. This model is validated for discriminating the ALDH1A1 inhibitors and non-inhibitors. Virtual screening protocol (VS) from this model identified four FDA-approved drugs, raloxifene, bazedoxifene, avanafil, and betrixaban as selective ALDH1A1 inhibitors. The molecular docking, dynamics, and water swap analysis also suggested these drugs to be promising ALDH1A1 inhibitors which were further validated for their CP resistance reversal potential by in-vitro analysis. The in-vitro enzymatic assay results indicated that raloxifene and bazedoxifene selectively inhibited the ALDH1A1 enzyme with IC50 values of 2.35 and 4.41 µM respectively, whereas IC50 values of both the drugs against ALDH2 and ALDH3A1 was >100 µM. Additional in-vitro studies with well-reported ALDH1A1 overexpressing A549 and MIA paCa-2 cell lines suggested that mafosfamide sensitivity was further ameliorated by the combination of both raloxifene and bazedoxifene. Collectively, in-silico and in-vitro studies indicate raloxifene and bazedoxifene act as promising adjuvants with CP that may improve the quality of treatment for cancer patients with minimal toxicities.

In silico guided designing of optimized benzochalcones derivatives as potent CYP1B1 inhibitors: An integrated in vitro and ONIOM study.

Cytochrome P4501B1 (CYP1B1) is reported to be overexpressed in various malignancies including ovarian, lung, lymph, and breast cancers. The overexpression of this enzyme is accountable for the biotransformation-based inactivation of some anti-cancer drugs i.e. Docetaxel, Paclitaxel, and Cisplatin. To circumvent solutions to this issue, the current study reports some optimized derivatives of benzochalcone as selective CYP1B1 inhibitors. The optimized derivatives were screened using some structure-based drug-designing approaches including molecular docking and molecular dynamics. The implemented approaches revealed that all the designed molecules demonstrated not only essential interactions with key amino acid residues but also maintained stability within the active site of CYP1B1. Furthermore, to validate the in-silico results and develop a SAR, the designed molecules were subsequently synthesized and tested for their ability to selectively inhibit CYP1B1 over CYP1A1 using well established EROD assay. This assay results suggested that compounds 1(c), 1(d), and 1(e) are eightfold more selective CYP1B1 inhibitors over CYP1A1 with IC50 values ranging from 0.06 to 0.09 µM respectively. Among these, compound 1(d) manifested potent inhibitory activity i.e. IC50 of 0.06 µM with 24 folds selectivity over 1A1. To have a better insight into the binding pattern of 1(d) within CYP1B1 and precisely compute binding affinity for 1(d)-CYP1B1 complex, one of the advanced QM/MM approaches i.e. ONIOM has been implemented. Where 1(d)-CYP1B1 complex conferred comparable binding affinity in terms of ΔG (kcal/mol) with that of ANF-CYP1B1 complex. This research could provide a suitable starting point for the development of more potent multi-functional compounds with CYP1B1 inhibitory activity.

Preparation and Characterisation of Liposomes of Bergenia Ciliata Extract and Evaluation of their Hepatoprotective Activity.

Acute liver damage (ALD) can cause biochemical and pathological changes, which can lead to major complications and even death. The goal of the study was to examine the therapeutic efficacy of liposomes of Bergenia ciliata extract against thioacetamide-induced liver damage in rats. Liposomal batches of B. ciliata extract were prepared by altering the kind and amount of phospholipids and characterized through various physiochemical properties such as laser diffraction, TEM, encapsulation efficiency, stability and in-vitro release studies. In-vivo hepatoprotective studies were performed on TAA-induced acute hepatic damage model. Further, in-silico studies of bergenin against the three hepatic damage markers viz. TGF-ß1, TNF-α and interleukin-6 were also performed. Laser diffraction and TEM showed that most stable liposome batch of B. ciliata extract were in the range of 678-1170 nm with encapsulation efficiency of 84.3±3.5. Extract was found to be rapidly dissociated from B. ciliata liposomes in HCl than PBS, according to in-vitro release data. In-vivo data revealed a significant decline in LFT indicators, amelioration of pathological changes and high bergenin bioavailability in the liposomal group. Protective activity of bergenin against ALD targets like TGF-ß1, TNF-α and interleukin-6 was anticipated via molecular docking research. As a result, the current findings of the study indicate that B. ciliata liposomes and bergenin have promising ameliorative potential in the management of ALD.

Knowledge, attitude and awareness among diabetic vs. non-diabetic patients about the association between diabetes and oral health.

Background: Global prevalence of diabetes is rapidly increasing with an estimate to affect 593 million worldwide by 2035. Current evidence clearly states an association between oral diseases and diabetes mellitus with manifestations like periodontitis, peri-implantitis, xerostomia, etc. Despite this obvious link, knowledge, awareness and attitude of general population towards this are not fully understood. Aims: To assess public knowledge and awareness on association between diabetes and oral health and assess their attitude towards oral hygiene care and maintenance. Methods and Materials: A three-part structured questionnaire was developed with multiple choice questions and circulated among patients visiting a private dental college. A total of 502 questionnaires were evaluated, and results were statistically analysed. Statistical Analysis Used: Student-t test and Chi-square test using SPSS software. Results: Majority of the participants were male and lived in urban area. 41.8% respondents had diabetes, out of which 86.7% had no awareness of the type. A significant number of non-diabetic individuals had awareness of excessive sugar intake as a cause of diabetes. Greater number of diabetic patients (96.7%) reported dry mouth, whereas only 53.3% had periodontal complications. 90% participants use tooth brush as oral hygiene aid. Only 10.6% participants follow regular dental visits. Majority of subjects (60.6%) listed their friends and family as major source of information. Conclusion: More people are aware of systemic complications of diabetes as compared to oral problems. A better interdisciplinary relationship is required among dentists and physicians to improve knowledge and awareness of general population.

Ruptured Splenic Abscess with Pneumoperitoneum: A Rare Presentation

Splenic abscess is a rare entity encountered during clinical practice, with a high mortality rate. Formation of gas in splenic abscess is usually localized to the left upper quadrant of the abdomen. Here we report a case where the splenic abscess ruptured and presented with generalized peritonitis. The erect chest radiograph showed free air under the right dome of the diaphragm, thus masquerading a hollow viscera perforation (most common cause of pneumoperitoneum).

Association of VEGF -2549 I/D and VEGF +936 C/T Polymorphisms with Chronic Kidney Disease in North-West Indian Patients.

Introduction: Chronic kidney disease (CKD) is a complex multifactorial disease in which both genetic and environmental factors influence the onset, development and progression of disease. The genetic variations in the vascular endothelial growth factor (VEGF) can influence levels of VEGF protein expression, and thus, susceptibility to progression of kidney diseases. The aim of the present study was to evaluate the association of VEGF-2549 I/D and VEGF +936 C/T polymorphisms in CKD stage V patients from North-West India. Methods: In this case-control study, 166 patients and 166 controls were analyzed. DNA samples were screened for VEGF -2549I/D and VEGF +936 C/T polymorphisms using polymerase chain reaction-based (PCR) methods. Results: The genotype frequency of VEGF -2549 I/D was significantly different between patients and controls (P < 0.05). ID genotype of VEGF -2549 I/D polymorphism was significantly associated with decreased risk of CKD (P = 0.009). Genetic model analysis of VEGF -2549 I/D polymorphism revealed a significantly decreased risk of CKD in co-dominant (P = 0.009), dominant (P = 0.021), and over-dominant (P = 0.012) models. Genotype and allele frequency of VEGF +936 C/T polymorphism was not significantly different between the patient and control groups. Genotype combination analysis revealed that ID-CT genotype combination of VEGF -2549 I/D and VEGF +936 C/T polymorphisms was associated with decreased CKD risk (P = 0.047). Conclusion: VEGF -2549 ID genotype and ID-CT genotype combination of VEGF -2549 I/D and VEGF +936 C/T polymorphisms was significantly associated with reduced CKD risk in North-West Indians.

Myopia, its prevalence, current therapeutic strategy and recent developments: A Review.

Myopia is a widespread and complex refractive error in which a person's ability to see distant objects clearly is impaired. Its prevalence rate is increasing worldwide, and as per WHO, it is projected to increase from 22% in 2000 to 52% by 2050. It is more prevalent in developed, industrial areas and affects individuals of all ages. There are a number of treatments available for the control of myopia, such as glasses, contact lenses, laser surgery, and pharmaceuticals agents. However, these treatments are less beneficial and have significant side effects. A novel molecule, 7-methylxanthine (7-MX), has been found to be a highly beneficial alternate in the treatment of myopia and excessive eye elongation. Many preclinical and clinical studies showed that 7-MX is effective for the treatment of myopia and is presently under phase II of clinical investigation. We have also investigated preclinical toxicity studies such as acute, sub-acute, sub-chronic, and chronic on rats. In these studies, 7-MX was found to be non-toxic as compared to other reported anti-myopic agents. Moreover, as an ideal drug, 7-MX is observed to have no or low toxicity, brain permeability, non-allergic, higher oral administration efficacy, and low treatment costs and thus qualifies for the long-term treatment of myopia. This review article on 7-MX as an alternative to myopia treatment will highlight recent findings from well-designed preclinical and clinical trials and propose a potential future therapy.

Micro RNAs as Emerging Therapeutic Targets in Liver Diseases.

MicroRNAs (MiRNAs) are endogenous non-coding small RNA molecules that regulate gene expression in plants, animals and some viruses. Both normal and pathological liver processes are regulated by miRNAs. Recent research indicated that miRNAs have been implicated in liver diseases caused by viral hepatitis (Hepatitis B and Hepatitis C), metabolic problems, alcohol and drug abuse. Because altered miRNA expression is linked to liver metabolic dysregulation, liver damage, liver fibrosis, and tumour growth, miRNAs are promising therapeutic targets for the detection and treatment of liver diseases. In this review, we summarise the current knowledge about the role of microRNAs in acute and chronic liver diseases, including hepatocellular carcinoma. We cover the miRNA-based therapy for liver disorders as well as the use of miRNAs as biomarkers for early diagnosis, prognosis and assessment of liver diseases. The investigation of miRNAs in liver diseases will provide a better understanding of the pathogeneses, identification of biomarkers and therapeutic targets for liver diseases in the future.

Survival and outcomes of tocilizumab use in severe and critically ill Covid-19 patients not responding to steroids

BackgroundMortality and morbidity are highest in severe and critically ill patients with COVID -19 pneumonia. We used interleukin-6 (IL-6) receptor inhibitor, tocilizumab in the above patients who failed to show any clinical improvement after initial treatment with steroids. MethodsThis is a retrospective observational study conducted at a tertiary care hospital in India. Severe and critical COVID-19 patients, who got admitted to intensive care unit and subsequently received tocilizumab were included. Patients who worsened clinically or had no change in oxygen requirement even after 24hrs of receiving intravenous methylprednisolone at a dose of 1-2mg/kg/day received a maximum total dose of 800mg of intravenous tocilizumab. The day 28 all-cause mortality and progression to mechanical ventilation were the primary outcome measures. Clinical improvement and oxygen requirements after tocilizumab administration along with trends in inflammatory markers and secondary infections rates were also noted. ResultsA total of 51 patients who did not show clinical improvement even after 24 hours of intravenous steroids had received tocilizumab. In these patients, there was a significant decrease in oxygen requirement and clinical progression by day 7 of tocilizumab administration. Baseline median values of CRP (114.2 mg/L), IL-6 (69.8 pg/ml) and neutrophil-lymphocyte ratio (12.4) in these patients were elevated. Out of these, only CRP showed a significant decrease after the drug administration. 13 (26.5%) of the 49 patients on non-invasive oxygen support progressed to mechanical ventilation and the day 28 all-cause mortality was 10/51(19.6%). 10(19.6%) of the 51 patients had life threatening infections. ConclusionEarly and timely administration of tocilizumab is a viable option in selected severe and critical COVID-19 patients who do not respond to initial steroids. When given along with steroids, a high suspicion of secondary infections should be kept.

Worsening Lower Jaw Swelling and Pain in a Teenager: Differential Diagnosis and Management.

Giant cell granuloma is a rare, benign non-neoplastic, aggressive tumor that originates mainly from the maxilla and mandible. It affects all age groups and is more commonly seen in children. We describe a 17-year-old female that presented to the Pediatrics Emergency room with a history of right lower jaw pain. Examination revealed a bone-like buccal vestibular swelling on the lower right tooth, a bone-like lingual swelling, and a pink gingival overgrowth lesion. The biopsy of the lesion revealed a central giant cell granuloma. Tissue biopsy with histopathological examination is diagnostic and surgical excision is the gold standard of treatment.

Fetal Gallstones in a Newborn after Maternal COVID-19 Infection.

Fetal gallstones are rare incidental findings on ultrasound during pregnancy. We describe a newborn girl with gallstones that was born to a mother who had COVID-19 infection during her last trimester. The baby remained asymptomatic, and the stones resolved spontaneously without any treatment or complications within six weeks of birth. Several conditions predispose to fetal gallstones, and it is unclear if the recent maternal COVID-19 infection had any role in the occurrence of these abnormalities or was merely coincidental. This is the first case describing an association of fetal gallstones with a COVID-19 infection in pregnancy.

Leishmania type II dehydrogenase is essential for parasite viability irrespective of the presence of an active complex I.

Type II NADH dehydrogenases (NDH2) are monotopic enzymes present in the external or internal face of the mitochondrial inner membrane that contribute to NADH/NAD+ balance by conveying electrons from NADH to ubiquinone without coupled proton translocation. Herein, we characterize the product of a gene present in all species of the human protozoan parasite Leishmania as a bona fide, matrix-oriented, type II NADH dehydrogenase. Within mitochondria, this respiratory activity concurs with that of type I NADH dehydrogenase (complex I) in some Leishmania species but not others. To query the significance of NDH2 in parasite physiology, we attempted its genetic disruption in two parasite species, exhibiting a silent (Leishmania infantum, Li) and a fully operational (Leishmania major, Lm) complex I. Strikingly, this analysis revealed that NDH2 abrogation is not tolerated by Leishmania, not even by complex I-expressing Lm species. Conversely, complex I is dispensable in both species, provided that NDH2 is sufficiently expressed. That a type II dehydrogenase is essential even in the presence of an active complex I places Leishmania NADH metabolism into an entirely unique perspective and suggests unexplored functions for NDH2 that span beyond its complex I-overlapping activities. Notably, by showing that the essential character of NDH2 extends to the disease-causing stage of Leishmania, we genetically validate NDH2-an enzyme without a counterpart in mammals-as a candidate target for leishmanicidal drugs.

Rise of silicene and its applications in gas sensing.

Reviewing a subject is done to provide an insight into theoretical and conceptual background of the study. Looking back into the history of an emerging field and summarizing it in a few pages is a herculean task. Anyway, it was imperative to write a few words about the rise of silicene, its properties, and its applications as gas sensors. Currently, silicene is a growing field of interest. It is probably one of the most studied materials nowadays and scientists and researchers are studying it because of its intriguing electronic properties and potential applications in nanoelectronics. Various experimental and theoretical investigations are going on worldwide to explore the various aspects of this field. It is essential to review the literature based on investigations by various scientists in this field.