Enhanced fetal hemoglobin production via dual-beneficial mutation editing of the HBG promoter in hematopoietic stem and progenitor cells for β-hemoglobinopathies.

Background: Sickle cell disease (SCD) and β-thalassemia patients with elevated gamma globin (HBG1/G2) levels exhibit mild or no symptoms. To recapitulate this natural phenomenon, the most coveted gene therapy approach is to edit the regulatory sequences of HBG1/G2 to reactivate them. By editing more than one regulatory sequence in the HBG promoter, the production of fetal hemoglobin (HbF) can be significantly increased.

Federated learning based fire detection method using local MobileNet.

Fire is a dangerous disaster that causes human, ecological, and financial ramifications. Forest fires have increased significantly in recent years due to natural and artificial climatic factors. Therefore, accurate and early prediction of fires is essential.

An Assessment of the Catalytic and Adsorptive Performances of Cellulose Acetate-Based Composite Membranes for Oil/Water Emulsion Separation.

Cellulose acetate (CA) mixed-matrix membranes incorporating polyvinylpyrrolidone (PVP), bentonite (B or Ben), graphene oxide (GO), and titanium dioxide (TiO) were prepared by the phase inversion separation technique for oil/water separation. An investigation was performed where the mixed-matrix membrane was tested for the separation performance of hydrophilic and hydrophobic surface properties. An ultrafiltration experiment at the laboratory scale was used to test dead-end ultrafiltration models developed for the treatment performances of oily wastewater under dynamic full-scale operating conditions.

Ectopic expression of choline oxidase () gene from confers drought stress tolerance in transgenic sugarcane.

Unlabelled: Drought is a serious problem that impacts sugarcane production and productivity worldwide. In this current investigation, a codon-optimized choline oxidase () gene was transformed into hybrid cultivar Co 86032 through -mediated transformation. The transgenic events with the gene driven by the portubi882 (PD2) promoter accumulated elevated levels of glycine betaine (5 - 10µg/g) whereas untransformed control plants accumulated less than 1.

Management of Disseminated Rhinosporidiosis: Experience From a Single Tertiary Institution.

Objective: This study aims to present a series of patients with disseminated rhinosporidosis with diagnostic and therapeutic features.

Methods: A retrospective study was conducted in a tertiary health care centre in South India from 2007 to 2020 with disseminated rhinosporidiosis. Twelve patients with multiple sites of involvement like the nose, nasopharynx, oropharynx, larynx, lacrimal sac and skin were included in the study.

Polo-like Kinase 1 Predicts Lymph Node Metastasis in Middle Eastern Colorectal Cancer Patients; Its Inhibition Reverses 5-Fu Resistance in Colorectal Cancer Cells.

Polo-like kinase 1 (PLK1) is a serine/threonine-protein kinase essential for regulating multiple stages of cell cycle progression in mammals. Aberrant regulation of PLK1 has been observed in numerous human cancers and is linked to poor prognoses. However, its role in the pathogenesis of colorectal cancer (CRC) in the Middle East remains unexplored.

Solar powered integrated multi sensors to monitor inland lake water quality using statistical data fusion technique with Kalman filter.

This study proposes a data-driven statistical model using multi sensor fusion and Kalman filtering for real-time water quality assessment in lakes. A recursive estimation technique, the Kalman Filter, is employed to handle uncertainties and enhance computational efficiency. The fusion process integrates data from sensors monitoring parameters like chlorophyll concentration, surface water elevation, temperature, and precipitation, producing Markov features to capture temporal transitions and environmental dynamics.

Endocytosis as a critical regulator of hematopoietic stem cell fate -implications for hematopoietic stem cell and gene therapy.

Hematopoietic stem cells (HSCs) have emerged as one of the most therapeutically significant adult stem cells, paving way for a range of novel curative regimens over decades. HSCs are transplanted, either directly or post restorative genetic engineering in order to repopulate a healthy hematopoietic homeostasis in patients with disorders affecting the blood and immune cells. Despite being an extensively studied system, the maintenance and expansion of functional HSCs ex vivo remains a major bottleneck.

Selective FFR testing in suspected stable angina in clinical practice - initial experiences.

Coronary CT angiography (CTA) derived fractional flow reserve (FFR) is recommended for physiological assessment in intermediate coronary stenosis for guiding referral to invasive coronary angiography (ICA). In this study, we report real-world data on the feasibility of implementing a CTA/FFR test algorithm as a gatekeeper to ICA at referral hospitals. Retrospective all-comer study of patients with new onset stable symptoms and suspected coronary stenosis (30-89%) by CTA.

Precise correction of a spectrum of β-thalassemia mutations in coding and non-coding regions by base editors.

β-thalassemia/HbE results from mutations in the β-globin locus that impede the production of functional adult hemoglobin. Base editors (BEs) could facilitate the correction of the point mutations with minimal or no indel creation, but its efficiency and bystander editing for the correction of β-thalassemia mutations in coding and non-coding regions remains unexplored. Here, we screened BE variants in HUDEP-2 cells for their ability to correct a spectrum of β-thalassemia mutations that were integrated into the genome as fragments of .

Promoting the Anticancer Activity with Multidentate Furan-2-Carboxamide Functionalized Aroyl Thiourea Chelation in Binuclear Half-Sandwich Ruthenium(II) Complexes.

A new set of binuclear arene ruthenium complexes [Ru(cymene)(k-NOS)(L1-L3)Cl] () encompassing furan-2-carboxamide-based aroylthiourea derivatives () was synthesized and characterized by various spectral and analytical techniques. Single-crystal XRD analysis unveils the N^O and N^S mixed monobasic bidentate coordination of the ligands constructing N, S, Cl/N, O, and Cl legged piano stool octahedral geometry. DFT analysis demonstrates the predilection for the formation of stable arene ruthenium complexes.

Phytochemical Screening, Molecular Docking, ADME Properties, and Antioxidant, Anticancer, and Antidiabetic Activity of Marine Halophyte (L.) Dumort.

Medicinally valuable components derived from natural resources are highly desirable as prospective alternatives to synthetic drugs to treat fatal diseases, such as cancer and diabetes mellitus. (L.) Dumort () () is a halophyte plant that can thrive in saline environments and possesses excellent medicinal properties.

SMART-lipid nanoparticles enabled mRNA vaccine elicits cross-reactive humoral responses against the omicron sub-variants.

The continual emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has necessitated the development of broad cross-reactive vaccines. Recent findings suggest that enhanced antigen presentation could lead to cross-reactive humoral responses against the emerging variants. Toward enhancing the antigen presentation to dendritic cells (DCs), we developed a novel shikimoylated mannose receptor targeting lipid nanoparticle (SMART-LNP) system that could effectively deliver mRNAs into DCs.

Cancer stem cells in head and neck squamous cell carcinoma and its associated markers: A review.

Evidences of the current research say that cancer is multifactorial with varied mechanisms of origin. Most theories evolve either intrinsic (genetic) or extrinsic factors like tobacco and alcoholism as the major cause of oral cancer in India. There is growing evidence that human papilloma virus may act as a co-carcinogen, along with tobacco, in the causation of cancers.

PLK1 and FoxM1 expressions positively correlate in papillary thyroid carcinoma and their combined inhibition results in synergistic anti-tumor effects.

Polo-like kinase 1 (PLK1; also known as serine/threonine-protein kinase PLK1) serves as a central player in cell proliferation, exerting critical regulatory roles in mitotic processes and cell survival. We conducted an analysis of PLK1 protein expression in a large cohort of samples from papillary thyroid carcinoma (PTC) patients and examined its functional significance in PTC cell lines, both in vitro and in vivo. PLK1 overexpression was noted in 54.

Base editing of key residues in the BCL11A-XL-specific zinc finger domains derepresses fetal globin expression.

BCL11A-XL directly binds and represses the fetal globin (HBG1/2) gene promoters, using 3 zinc-finger domains (ZnF4, ZnF5, and ZnF6), and is a potential target for β-hemoglobinopathy treatments. Disrupting BCL11A-XL results in derepression of fetal globin and high HbF, but also affects hematopoietic stem and progenitor cell (HSPC) engraftment and erythroid maturation. Intriguingly, neurodevelopmental patients with ZnF domain mutations have elevated HbF with normal hematological parameters.

An impactful prospective study on pulmonary tuberculosis in geriatric populations besides its clinical outcomes and implications in the Indian subcontinent.

Objective: Geriatric populations are most at risk for the tuberculosis pandemic, and as people age, the rate of infection rises steadily and drastically. Geriatric individuals frequently experience diagnostic challenges with a wide range of comorbidities, but employing all available standard and novel methods to diagnose any infection is crucial. The prophylactic and therapeutic management for the geriatric population presents a significant difficulty and challenge in assessing an appropriate and effective therapeutic outcome due to prolonged drug therapy and adverse drug reactions.

PLK1 and PARP positively correlate in Middle Eastern breast cancer and their combined inhibition overcomes PARP inhibitor resistance in triple negative breast cancer.

Background: Despite advancements in treatment approaches, patients diagnosed with aggressive breast cancer (BC) subtypes typically face an unfavorable prognosis. Globally, these cancers continue to pose a significant threat to women's health, leading to substantial morbidity and mortality. Consequently, there has been a significant struggle to identify viable molecular targets for therapeutic intervention in these patients.

Pan-India influenza-like illness (ILI) and Severe acute respiratory infection (SARI) surveillance: epidemiological, clinical and genomic analysis.

Background: Over time, COVID-19 testing has significantly declined across the world. However, it is critical to monitor the virus through surveillance. In late 2020, WHO released interim guidance advising the use of the existing Global Influenza Surveillance and Response System (GISRS) for the integrated surveillance of influenza and SARS-CoV-2.

Current approaches and potential challenges in the delivery of gene editing cargos into hematopoietic stem and progenitor cells.

Advancements in gene delivery and editing have expanded the applications of autologous hematopoietic stem and progenitor cells (HSPCs) for the treatment of monogenic and acquired diseases. The gene editing toolbox is growing, and the ability to achieve gene editing with mRNA or protein delivered intracellularly by vehicles, such as electroporation and nanoparticles, has highlighted the potential of gene editing in HSPCs. Ongoing phase I/II clinical trials with gene-edited HSPCs for β-hemoglobinopathies provide hope for treating monogenic diseases.

Endoscope-Assisted Removal of Post-Traumatic Orbital Epidermoid Inclusion Cyst: A Useful Adjunct.

Orbital epidermoid cysts are uncommon lesions within the bony orbit with varied symptomatology related to both the eye and the sino-nasal system. They are often slow-growing cystic masses which may cause facial asymmetry and visual loss due to pressure symptoms. Cross-sectional imaging such as computed tomography and magnetic resonance imaging are contributory and useful for assessment of the size and actual extent and should be mandatory before planning any surgical intervention.