Assessment of climate change impact on meteorological variables of Indravati River Basin using SDSM and CMIP6 models.

Climate change, one of the most pressing issues of the twenty-first century, threatens the long-term stability and short-term variability of water resources. Variations in precipitation and temperature will influence runoff and water availability, creating significant challenges as demand for potable water increases. This study addresses a critical literature gap by employing the Statistical Downscaling Model (SDSM) to downscale Global Climate Model (GCM) outputs for the Indravati River Basin, India.

Validation of a commercially available CAD-system for lung nodule detection and characterization using CT-scans.

Objectives: This study aims to externally validate a commercially available Computer-Aided Detection (CAD)-system for the automatic detection and characterization of solid, part-solid, and ground-glass lung nodules (LN) on CT scans.

Methods: This retrospective study encompasses 263 chest CT scans performed between January 2020 and December 2021 at a Dutch university hospital. All scans were read by a radiologist (R1) and compared with the initial radiology report.

A roadmap for ribosome assembly in human mitochondria.

Mitochondria contain dedicated ribosomes (mitoribosomes), which synthesize the mitochondrial-encoded core components of the oxidative phosphorylation complexes. The RNA and protein components of mitoribosomes are encoded on two different genomes (mitochondrial and nuclear) and are assembled into functional complexes with the help of dedicated factors inside the organelle. Defects in mitoribosome biogenesis are associated with severe human diseases, yet the molecular pathway of mitoribosome assembly remains poorly understood.

AKR1B1 drives hyperglycemia-induced metabolic reprogramming in MASLD-associated hepatocellular carcinoma.

Background & Aims: The mechanism behind the progressive pathological alteration in metabolic dysfunction-associated steatotic liver disease/steatohepatitis (MASLD/MASH)-associated hepatocellular carcinoma (HCC) is poorly understood. In the present study, we investigated the role of the polyol pathway enzyme AKR1B1 in metabolic switching associated with MASLD/MASH and in the progression of HCC.

Methods: AKR1B1 expression was estimated in the tissue and plasma of patients with MASLD/MASH, HCC, and HCC with diabetes mellitus.

Apoptosis-driven synergistic anti-cancer efficacy of ethyl acetate extract of Memecylon sisparense Gamble leaves and doxorubicin in in-vitro and in-vivo models of triple-negative breast cancer.

In the spectrum of breast neoplasms, approximately 15 to 20% of all diagnosed cases are triple-negative breast carcinoma. TNBC grows and spreads faster than other invasive breast cancers and has a worse prognosis. The existing therapies and chemotherapeutic drugs have several limitations, so the development of safe and affordable treatment options is currently in demand.

AKR1B1 inhibition using NARI-29-an Epalrestat analogue-alleviates Doxorubicin-induced cardiotoxicity via modulating Calcium/CaMKII/MuRF-1 axis.

The clinical use of doxorubicin (Dox) is narrowed due to its carbonyl reduction to doxorubicinol (Doxol) implicating resistance and cardiotoxicity. Hence, in the present study we have evaluated the cardioprotective effect of AKR1B1 (or aldose reductase, AR) inhibitor NARI-29 (epalrestat (EPS) analogue) and its effect in the Dox-modulated calcium/CaMKII/MuRF1 axis. Initially, the breast cancer patient survival associated with AKR1B1 expression was calculated using Kaplan Meier-plotter (KM-plotter).

Ready-to-use vertical flow paper device for instrument-free room temperature reverse transcription.

Paper-based nucleic acid detection and diagnosis are currently gaining much interest in point-of-care (POC) applications. The major steps involved in any nucleic acid amplification testing (NAAT) based diagnostics are nucleic acid isolation, reverse transcription (RT) (in the case of RNA), amplification and detection. RT is an important step in quantifying the viral load in case of disease diagnosis as well as quantifying gene expression levels in other molecular studies.

Perillyl alcohol inhibits keratinocyte proliferation and attenuates imiquimod-induced psoriasis like skin-inflammation by modulating NF-κB and STAT3 signaling pathways.

Psoriasis is a chronic inflammatory and proliferative skin disease characterized by pathological skin lesions which significantly impact the quality of life. Recent studies have been proven that inhibitors of farnesyltransferase enzyme showed significant anti-psoriatic activity. Perillyl alcohol (POH) is one such natural molecule having anti proliferative, anti-inflammatory and anti-oxidant properties by inhibiting farnesyltransferase enzyme which further down regulates NF-κB and STAT3 via Ras/Raf/MAPK pathway.

An insight of nanogels as novel drug delivery system with potential hybrid nanogel applications.

Nanogels are cross-linked, nano-sized hydrogels with dimensions ranging from 20 to 200 nm. Nanogel-based nanoplatforms have proven to be an excellent choice for pharmaceutical formulations. Nanosystems have properties that are very useful in polymeric drug delivery applications, and their particular strength is that they have these nanosystemic properties and can thus merge with polymeric materials.

Total synthesis of biselide A.

A total synthesis of the marine macrolide biselide A is described that relies on an enantiomerically enriched α-chloroaldehyde as the sole chiral building block. Several strategies to construct the macrocycle are presented including a macrocyclic Reformatsky reaction that ultimately provides access to the natural product in a longest linear sequence of 18 steps. Biological testing of synthetic biselide A suggests this macrolide disrupts cell division through a mechanism related to the regulation of microtubule cytoskeleton organization.

Diversity-oriented synthesis of glycomimetics.

Glycomimetics are structural mimics of naturally occurring carbohydrates and represent important therapeutic leads in several disease treatments. However, the structural and stereochemical complexity inherent to glycomimetics often challenges medicinal chemistry efforts and is incompatible with diversity-oriented synthesis approaches. Here, we describe a one-pot proline-catalyzed aldehyde α-functionalization/aldol reaction that produces an array of stereochemically well-defined glycomimetic building blocks containing fluoro, chloro, bromo, trifluoromethylthio and azodicarboxylate functional groups.

More and more of less and less: Is genomics-based breeding of dry direct-seeded rice (DDSR) varieties the need of hour?

Rice is a staple food for half of the world's population. Changing climatic conditions, water and labour scarcity are the major challenges that shall limit future rice production. Dry direct-seeded rice (DDSR) is emerging as an efficient, resources conserving, mechanized, climate smart and economically viable strategy to be adopted as an alternative to puddled transplanted rice (TPR) with the potential to address the problem of labour-water shortages and ensure sustainable rice cultivation.

The significant impact of mechanically-induced phase transformation on cellular functionality of biomedical austenitic stainless steel.

The implant surface and tissue experience strain when micro-motion occurs at the bone-implant interface under physiological loading. Moreover, strain is also introduced on the surface during mechanical processing of biomedical devices. Both these situations can induce phase transformation depending on the degree of stability of the microstructural constituents.

A counterintuitive stereochemical outcome from a chelation-controlled vinylmetal aldehyde addition leads to the configurational reassignment of phormidolide A.

As part of our ongoing studies towards the total synthesis of phormidolide A (1), we explored the chelation-controlled vinylmetal addition of iodide 2 to aldehyde 3 to install the reported 17S configuration. While the stereochemical outcome of this reaction was opposite to that expected, detailed NMR comparisons with the previously reported triacetonide derivative of phormidolide A (18) highlighted that the major adduct was a better match to the natural product. The synthesis of three model acetonides and detailed spectroscopic comparisons to the triacetonide derivative of phormidolide A supports a reassignment of seven of the 11 stereocentres in phormidolide A (1a).

Intranasal Zotepine Nanosuspension: intended for improved brain distribution in rats.

Background: Zotepine (ZTP), an antipsychotic drug is well tolerated and particularly effective for treating negative symptoms of psychosis. But is limited by low oral bioavailability caused by substantial first pass metabolism and thereby less amount of drug reaches the brain due to blood brain barrier (BBB).

Objectives: Since ZTP displays dose dependent side effects, purpose of the contemporary study is to develop zotepine loaded nanosuspension (ZTP-NS) for increased brain targeting in rats at lower doses.

Protective effects of ambroxol in psoriasis like skin inflammation: Exploration of possible mechanisms.

The purpose of this study was to investigate the protective effects of ambroxol in psoriasis-like skin inflammation both in vitro and in vivo and delineate the molecular mechanism of ambroxol. Our data demonstrated that ambroxol has an imperative role in inhibiting the lipopolysaccharide (LPS) stimulated nitrite levels, total cellular and mitochondrial reactive oxygen species level which was determined by Griess assay, DCFDA, and MitoSOX Red staining, respectively. We found that ambroxol remarkably reduced imiquimod (IMQ) induced epidermal hyperplasia, psoriasis area and severity index (PASI) scoring, splenomegaly, skin, and ear fold thickness.

Abietic acid attenuates RANKL induced osteoclastogenesis and inflammation associated osteolysis by inhibiting the NF-KB and MAPK signaling.

Osteoporosis is a major debilitating cause of fractures and decreases the quality of life in elderly patients. Bone homeostasis is maintained by bone forming osteoblasts and bone resorpting osteoclasts. Substantial evidences have shown that targeting osteoclasts using natural products is a promising strategy for the treatment of osteoporosis.

Intranasal delivery of nanoparticle encapsulated tarenflurbil: A potential brain targeting strategy for Alzheimer's disease.

Poor brain penetration of tarenflurbil (TFB) was one of the major reasons for its failure in phase III clinical trials conducted on Alzheimer's patients. Thus there is a tremendous need of developing efficient delivery systems for TFB. This study was designed with the aim of improving drug delivery to brain through intranasally delivered nanocarriers.

Challenges in Diagnosis and Management of Paget's Disease of the Breast-a Retrospective Study.

Paget's disease of the breast is uncommon and patients may present with nipple discharge, eczema, plaque or nipple destruction with or without a lump. The aim of the present study was to evaluate the presentation, clinicopathological features and treatment given for patients presenting with Paget's disease of the breast. We performed a retrospective analysis of medical records of patients who were treated at our centre for Paget's disease of the breast from 2006-2011.

Gastric metastases from breast cancer: A report of two cases and review of literature.

Though breast cancer is a common cancer it rarely metastasizes to stomach. Lobular carcinoma is the most common histological type which presents with gastric metastases. The most common presentation is linitis plastica.

"Ovarian Metastases from Colorectal Cancer: Our Experience".

Ovarian metastases from colorectal cancer are uncommon and can present synchronously and metachronoulsy. Role of prophylactic oophorectomy for colorectal cancer is controversial and there is no definitive evidence to support it. A retrospective analysis of all the patients with colorectal cancer who had attended a single unit at our center have been analysed.

Mesopancreas in pancreatic cancer: where do we stand - review of literature.

Pancreatic cancer is associated with poor prognosis and surgery remains the main modality of treatment. Negative resection margin is an important prognostic factor for survival. Retropancreatic margin or the medial margin is the most common site of positive resection margin.

A Retrospective Study of Marjolin's Ulcer Over an Eleven Year Period.

Background: Marjolin's ulcer is a rare aggressive cutaneous malignancy occurring in previously occurred wounds. The most common aetiology is a burn wound involving extremities and squamous cell carcinoma is the most common variant.

Materials And Methods: A retrospective analyses of medical records of patients treated in a single unit with a diagnosis of Marjolin's ulcer was performed.