Quest for discovering novel CDK12 inhibitor.

CDK12 is essential for cellular processes like RNA processing, transcription, and cell cycle regulation, inhibiting cancer cell growth and facilitating macrophage invasion. CDK12 is a significant oncogenic factor in various cancers, including HER2-positive breast cancer, Anaplastic thyroid carcinoma, Hepatocellular carcinoma, prostate cancer, and Ewing sarcoma. It is also regarded as a potential biomarker, emphasizing its broader significance in oncology.

Laccase-based biocatalytic systems application in sustainable degradation of pharmaceutically active contaminants.

The outflow of pharmaceutically active chemicals (PhACs) exerts a negative impact on biological systems even at extremely low concentrations. For instance, enormous threats to human and aquatic species have resulted from the widespread use of antibiotics in ecosystems, which stimulate the emergence and formation of antibiotic-resistant bacterial species and associated genes. Additionally, it is challenging to eliminate these PhACs by employing conventional physicochemical water treatment techniques.

USP10 deubiquitinates and stabilizes CD44 leading to enhanced breast cancer cell proliferation, stemness and metastasis.

Despite extensive research, strategies to effectively combat breast cancer stemness and achieve a definitive cure remains elusive. CD44, a well-defined cancer stem cell (CSC) marker is reported to promote breast cancer tumorigenesis, metastasis, and chemoresistance. However, mechanisms leading to its enhanced expression and function is poorly understood.

Exploration of phytoconstituents of Medhya Rasayana herbs to identify potential inhibitors for through high-throughput screening.

(CST) is a key enzyme in sulfatide biosynthesis and regulation of the myelin sheath in the nervous system. To counter sulfatide accumulation with the deficiency of aryl sulfatase A, CST is considered a target protein in substrate reduction therapy in metachromatic leukodystrophy. In this study, 461 phytoconstituents from four herbs of Medhya Rasayana were screened using multi-pronged virtual screening methods including molecular docking, molecular dynamics (MD) simulation, and reverse pharmacophore analysis.

Phytoconstituents of Withania somnifera (L.) Dunal (Ashwagandha) unveiled potential cerebroside sulfotransferase inhibitors: insight through virtual screening, molecular dynamics, toxicity, and reverse pharmacophore analysis.

Cerebroside sulfotransferase (CST) is considered as therapeutic target for substrate reduction therapy (SRT) for metachromatic leukodystrophy (MLD). The present study evaluates the therapeutic potential of 57 phytoconstituents of Withania somnifera against CST. Using binding score cutoff ≤-7.

Estimating rate of lung function change using clinical spirometry data.

Rationale: In chronic obstructive pulmonary disease (COPD), accurately estimating lung function from electronic health record (EHR) data would be beneficial but requires addressing complexities in clinically obtained testing. This study compared analytic methods for estimating rate of forced expiratory volume in one second (FEV) change from EHR data.

Methods: We estimated rate of FEV change in patients with COPD from a single centre who had ≥3 outpatient tests spanning at least 1 year.

Nemo-like kinase blocks myeloid differentiation by targeting tumor suppressor C/EBPα in AML.

CCAAT/enhancer-binding protein α (C/EBPα), a key myeloid transcription factor, drives myeloid differentiation from blast cells by regulating the expression of granulocyte colony stimulating factor receptor and C/EBPε as required for promoting granulocyte differentiation. Here, we show that serine/threonine-protein kinase NLK, also known as Nemo-like kinase, physically associates with C/EBPα and phosphorylates it at multiple sites, including Ser21, Thr226, Thr230 and S234, leading to its ubiquitin-mediated degradation. Individual phospho-point mutants of C/EBPα could be phosphorylated by NLK, but a mutant with all phosphorylatable residues replaced by alanine resisted phosphorylation and degradation by NLK, as did the single point mutants.

Twist Proximity-Endowed Large Figure of Merit in a Band-Modulated CrI/1T-MoS Moiré Superlattice.

Moiré superlattices with a robust twist proximity effect in the low-dimensional regime can facilitate nanoscale thermoelectric devices. In pristine systems, the low efficiency and lack of proficient control of thermoelectric properties impede desirable advancements in the field of energy conversion. In the present study, we demonstrate remarkable macroscopic thermoelectric response as a consequence of microscopic band structure modulation via the twist proximity in an engineered CrI/1T-MoS moiré superlattice.

PGPR-Enabled bioremediation of pesticide and heavy metal-contaminated soil: A review of recent advances and emerging challenges.

The excessive usage of agrochemicals, including pesticides, along with various reckless human actions, has ensued discriminating prevalence of pesticides and heavy metals (HMs) in crop plants and the environment. The enhanced exposure to these chemicals is a menace to living organisms. The pesticides may get bioaccumulated in the food chain, thereby leading to several deteriorative changes in the ecosystem health and a rise in the cases of some serious human ailments including cancer.

Delineating the Acquired Genetic Diversity and Multidrug Resistance in Alcaligenes from Poultry Farms and Nearby Soil.

Alcaligenes faecalis is one of the most important and clinically significant environmental pathogens, increasing in importance due to its isolation from soil and nosocomial environments. The Gram-negative soil bacterium is associated with skin endocarditis, bacteremia, dysentery, meningitis, endophthalmitis, urinary tract infections, and pneumonia in patients. With emerging antibiotic resistance in A.

Efficacy and safety of spironolactone versus bicalutamide in female pattern hair loss: A retrospective comparative study.

Background: Female-pattern hair loss (FPHL) is characterized by decreased scalp hair density, thinning of hair shafts, and progressive miniaturization of hair follicles.

Objective: To compare the safety and efficacy of spironolactone versus bicalutamide in female pattern hair loss [FPHL].

Methods: The study design was retrospective, and all eligible females aged between 18 years and 50 years with FPHL were included.

Ring finger protein 138 inhibits transcription factor C/EBPα protein turnover leading to differentiation arrest in acute myeloid leukemia.

E3 ubiquitin ligase, ring finger protein 138 (RNF138) is involved in several biological processes; however, its role in myeloid differentiation or tumorigenesis remains unclear. RNAseq data from TNMplot showed that RNF138 mRNA levels are highly elevated in acute myeloid leukemia (AML) bone marrow samples as compared with bone marrow of normal volunteers. Here, we show that RNF138 serves as an E3 ligase for the tumor suppressor CCAAT/enhancer binding protein (C/EBPα) and promotes its degradation leading to myeloid differentiation arrest in AML.

Large thermoelectric transport in magnetically coupled CrI/1T-MoSvdW heterostructure via spin-charge interconversion.

Low-dimensional materials with prominent thermoelectric (TE) effect play a pivotal role in realizing state-of-the-art nanoscale TE devices. The fusion of TE effect with the magnetism through seamless integration of TE and magnetic materials in the 2D limit offers access to control longitudinal as well as transverse TE properties via magnetic proximity effect. Herein, we design a van der Waals (vdW) heterostructure of metallic 1T-MoSwith promising TE properties and a layer-dependent magnetic CrImaterial.

In Silico Structural Modeling and Binding Site Analysis of Cerebroside Sulfotransferase (CST): A Therapeutic Target for Developing Substrate Reduction Therapy for Metachromatic Leukodystrophy.

Cerebroside sulfotransferase (CST) is emerging as an important therapeutic target to develop substrate reduction therapy (SRT) for metachromatic leukodystrophy (MLD), a rare neurodegenerative lysosomal storage disorder. MLD develops with progressive impairment and destruction of the myelin sheath as a result of accumulation of sulfatide around the nerve cells in the absence of its recycling mechanism with deficiency of arylsulfatase A (ARSA). Sulfatide is the product of the catalytic action of cerebroside sulfotransferase (CST), which needs to be regulated under pathophysiological conditions by inhibitor development.

Endoscopic Ultrasound-Guided Glue Embolization for Left Gastric Artery Pseudoaneurysm Presenting as Hemosuccus Pancreaticus After Failed Radiological Intervention.

Hemosuccus pancreaticus is characterized by intermittent bleeding from the ampulla of Vater due to the rupture of a pseudoaneurysm. There are significant diagnostic and therapeutic challenges associated with this rare and potentially life-threatening condition. We present a rare case in an 18-year-old man who presented with recurrent episodes of hematemesis and melena due to hemosuccus pancreaticus as a result of a left gastric artery pseudoaneurysm.