Combined Kinetic and Computational Analysis of the Palladium-Catalyzed Formylation of Aryl Bromides.

Aryl aldehydes are key synthetic intermediates in the manufacturing of active pharmaceutical ingredients. They are generated on scale (>1000 kg) through the palladium-catalyzed formylation of aryl bromides using syngas (CO/H). The best-in-class catalyst system for this reaction employs di-1-adamantyl--butylphosphine (cataium A), palladium(II) acetate, and tetramethylethylenediamine.

The long-term impact of vaccine clinical research on national stakeholders involved: Experience from a low-income Country.

Clinical trials are the most rigorous scientific and regulated method to investigate the safety and efficacy of vaccines or drugs in pre-licensure stage. Clinical trial design and implementation are complex, time-consuming and involves close engagement with country's regulatory authority, clinical trial sites, investigators, and the healthcare system. Over the past few decades, a significant number of clinical trials have been conducted in low- and middle-income countries (LMICs), particularly in resource-limited settings.

Role of myeloid-derived suppressor and Th17/Treg cells in post-COVID-19 Rhino-Orbital mucormycosis cases.

Rhino-Orbital-Cerebral Mucormycosis (ROCM) cases increased sharply in India during the second COVID-19 wave. Due to uncontrolled hyperglycemia, prolonged steroid use, and high ferritin levels, the immune system was dysregulated throughout this surge. Our study examined post-COVID-19 ROCM patients' T regulatory cell (Treg), T helper 17 cell (Th17) and Myeloid derived suppressor cell (MDSC) levels before and after three months of treatment.

A selective small-molecule agonist of G protein-gated inwardly-rectifying potassium channels reduces epileptiform activity in mouse models of tumor-associated and provoked seizures.

Tumor associated epilepsy is a common and debilitating co-morbidity of brain tumors, for which inadequate treatments are available. Additionally, animal models suggest a potential link between seizures and tumor progression. Our group has previously described a mouse model of diffusely infiltrating glioma and associated chronic epilepsy.

Laparoscopic Cornuostomy: A Conservative Surgical Approach to Interstitial Pregnancy - A Case Report.

Interstitial pregnancy accounts for only 2%-4% of all ectopic pregnancies, however, it is associated with higher mortality rates as compared to other ectopic pregnancies, due to the associated risk of uterine rupture, and hemorrhage. A 35-year-old gravida 4 abortion 3 woman reported at the 8 week of gestation for antenatal care with comorbidity of protein C and protein S deficiency and recurrent pregnancy loss with for routine care. She was diagnosed as a case of interstitial pregnancy by transvaginal sonography and magnetic resonance imaging.

Retrograde aortic dissection encountered amidst nephrectomy for renal cell carcinoma with IVC thrombus - a case report.

Background: Management of RCC with IVC thrombus can be surgically challenging, particularly when the tumour thrombus extends above the diaphragm. Cardiopulmonary bypass is often employed to aid surgical removal of the tumour in such cases.

Case Presentation: We detail an instance of 67-year-old Male patient suffering from RCC with IVC thrombus, with the tumour thrombus extending into the right atrium, who developed on-table retrograde type A aortic dissection amidst the surgical procedure, thereby precluding cardiopulmonary bypass.

Antifungal activity of zinc oxide nanoparticles (ZnO NPs) on phytopathogen isolated from tomato plant in Nepal.

Fungal diseases pose a major threat to global agriculture, leading to reduced crop yields, health issues and significant economic impact. Application of nanoparticles are being explored in agriculture because of its ecofriendly as well as enhanced antimicrobial properties. In this study, using an aqueous extract of air-dried tea leaves, zinc oxide nanoparticles (ZnO NPs) are synthesized and it was characterized using various techniques such as X-ray diffraction, UV-Vis, FTIR spectroscopy and microscopic analysis.

Dexamethasone and IFN-γ primed mesenchymal stem cells conditioned media immunomodulates aberrant NETosis in SLE via PGE2 and IDO.

Background: Systemic Lupus Erythematosus (SLE) is characterized by dysregulated immune responses, with neutrophil extracellular traps (NETs) playing a significant role. NETs are recognized by autoantibodies in SLE patients, exacerbating pathology. Both excessive NET formation and impaired degradation contribute to SLE pathophysiology.

An insight into the role of innate immune cells in breast tumor microenvironment.

The immune background of breast cancer is highly heterogeneous and the immune system of the human body plays a dual role by both promoting and suppressing its progression. Innate immune cells are the first line of defense in the immune system and impart protection by identifying and interacting with foreign pathogens and cancer cells. Different innate immune cells like natural killer cells, macrophages, dendritic cells, and myeloid suppressor cells take part in hosting the cancer cells.

Cell-Based Covalent-Capture Deubiquitinase Assay for Inhibitor Discovery.

Ubiquitination is a post-translational modification that elicits a variety of cellular responses. Deubiquitinases (DUBs) remove ubiquitin moieties from proteins and modulate cellular processes by counteracting the ubiquitin ligase activities. Ubiquitination and deubiquitination processes are tightly regulated by different mechanisms and their dysregulation is associated with many diseases.

Small-Molecule Disruptors of the Interaction between Calcium- and Integrin-Binding Protein 1 and Integrin αβ as Novel Antiplatelet Agents.

Thrombosis, a key factor in most cardiovascular diseases, is a major contributor to human mortality. Existing antithrombotic agents carry a risk of bleeding. Consequently, there is a keen interest in discovering innovative antithrombotic agents that can prevent thrombosis without negatively impacting hemostasis.

Multi-location evaluation of field pea in Indian climates: eco-phenological dynamics, crop-environment relationships, and identification of mega-environments.

Characterization of crop-growing environments in relation to crop's genotypic performance is crucial to harness positive genotype-by-environment interactions (GEI) in systematic breeding programs. Given that, the study aimed to delineate the impact of diverse environments on crop phenology and yield traits of dwarf-statured field pea, pinpointing location(s) favoring higher yield and distinctiveness within breeding lines. We tested twelve field pea breeding lines across twenty locations in India, covering Central Zone (CZ), North Western Plain Zone (NWPZ), North Eastern Plain Zone (NEPZ), and Northern Hill Zone (NHZ).

Transient caspase-mediated activation of caspase-activated DNase causes DNA damage required for phagocytic macrophage differentiation.

Phagocytic macrophages are crucial for innate immunity and tissue homeostasis. Most tissue-resident macrophages develop from embryonic precursors that populate every organ before birth to lifelong self-renew. However, the mechanisms for versatile macrophage differentiation remain unknown.

Association between Usage of Prophylactic AYUSH Medicines and Disease Severity in COVID-19 Patients: A Retrospective Cohort Study.

Background: Prior vaccination is often studied for its impact on individuals' post-infection prognosis. Ayurveda, Yoga, Unani, Siddha and Homeopathy (AYUSH) medicines, advised by the Government of India as prophylaxis during the first wave of the coronavirus disease 2019 (COVID-19) pandemic, were consumed by the masses in 2020. A study was therefore undertaken to observe any association between the prior usage of AYUSH prophylactic medicines and post-infection severity as reported by recovered COVID-19 individuals.

Drug-resistant Mycobacterium tuberculosis among Nepalese patients at a tuberculosis referral center.

Background: Multidrug-resistant tuberculosis (MDR-TB), characterized by isoniazid and rifampicin resistance, is caused by chromosomal mutations that restrict treatment options and complicate tuberculosis management. This study sought to investigate the prevalence of pre-extensively drug-resistant (pre-XDR) and extensively drug-resistant (XDR) tuberculosis, as well as mutation pattern, in Nepalese patients with MDR/rifampicin-resistant (RR)-TB strains.

Methods: A cross-sectional study was conducted on MDR/RR-TB patients at the German Nepal Tuberculosis Project from June 2017 to June 2018.

EIDD-1931 Treatment Tweaks CYP3A4 and CYP2C8 in Arthritic Rats to Expedite Drug Interaction: Implication in Oral Therapy of Molnupiravir.

EIDD-1931 is the active form of molnupiravir, an orally effective drug approved by the United States Food and Drug Administration (USFDA) against COVID-19. Pharmacokinetic alteration can cause untoward drug interaction (drug-drug/disease-drug), but hardly any information is known about this recently approved drug. Therefore, we first investigated the impact of the arthritis state on the oral pharmacokinetics of EIDD-1931 using a widely accepted complete Freund's adjuvant (CFA)-induced rat model of rheumatoid arthritis (RA) after ascertaining the disease occurrence by paw swelling measurement and X-ray examination.

Implications of CD45RA and CD45RO T cell subsets in patients of chronic rhinosinusitis with nasal polyposis infected with Aspergillus flavus.

T cell subsets (CD4 and CD8) play a prominent role in the development of chronic rhinosinusitis with nasal polyposis (CRSwNP). Colonization with Aspergillus flavus is recognized as a trigger for the growth of nasal polyps. The fungal proteins initiate the recruitment of T cells into the nasal mucosa, which contributes to the progression of nasal polyps.

Bio-stimulants from medicinally and nutritionally significant plant extracts mitigate drought adversities in Zea mays through enhanced physiological, biochemical, and antioxidant activities.

Drought stress poses a substantial threat to global plant productivity amid increasing population and rising agricultural demand. To overcome this problem, the utilization of organic plant growth ingredients aligns with the emphasis on eco-friendly farming practices. Therefore, the present study aimed to assess the influence of 30 botanical extracts on seed germination, seedling vigor, and subsequent maize plant growth under normal and water deficit conditions.

Growth Factor Independence-1 (GFI-1) Gene Expression in Hematopoietic Stem Cell Lineage Differentiation in Low Birth Weight Newborns Compared With Normal Birth Weight Newborns at Term Pregnancy.

Introduction Low birth weight (LBW), which is a risk factor for noncommunicable diseases throughout life, is a significant public health concern. In addition to regulating myeloid cell differentiation and proliferation, a transcriptional repressor identified as growth factor independence-1 (GFI-1) is essential for hematopoietic stem cell maintenance and self-renewal. The current study was designed to compare the expression of the GFI-1 gene in the differentiation of hematopoietic stem cells in newborns with LBW and those with normal birth weight (NBW).

Shigella as a Cause of Diarrhea Hospitalization in Children Under Five: Evaluation by Conventional and Molecular Methods.

Background And Objectives: is an important cause of diarrhea in children under five, often missed by conventional laboratory methods. Blood in stools has always been a syndromic indicator for diarrhea, but most cases present with watery diarrhea without blood. This study aimed to determine the frequency of detected by molecular and conventional methods in children under five.

Nanotechnological advances in the treatment of epilepsy: a comprehensive review.

Epilepsy is one of the most prevalent chronic neurological disorders characterized by frequent unprovoked epileptic seizures. Epileptic seizures can develop from a broad range of underlying abnormalities such as tumours, strokes, infections, traumatic brain injury, developmental abnormalities, autoimmune diseases, and genetic predispositions. Sometimes epilepsy is not easily diagnosed and treated due to the large diversity of symptoms.

Safety and immunogenicity of conjugate vaccine for typhoid (Vi-DT): Finding from an observer-blind, active-controlled, randomized, non-inferiority, phase III clinical trial among healthy volunteers.

Typhoid fever is a significant public health concern with most of the sufferers between 15 and 25 y of age in Nepal. We undertook this study to demonstrate Vi polysaccharide conjugated with diphtheria toxoid (Vi-DT) conjugate vaccine which is non-inferior to Typbar typhoid conjugate vaccine, a Vi polysaccharide vaccine conjugated with tetanus toxoid (Vi-TT) with a focus on the adult population from Dhulikhel Hospital which was one of the total four sites in Nepal. In this study, we assigned the eligible participants in 1:1:1:1 ratio by block randomization, and stratified into three age groups (6 months to less than 2 y, 2 y to less than 18 y, and 18 y to 45 y), allotted to Group A, B, C, and D.