In silico network pharmacology analysis and molecular docking validation of Swasa Kudori tablet for screening druggable phytoconstituents of asthma.

Traditional medicines are impactful in treating a cluster of respiratory-related illnesses. This paper demonstrates screening active, druggable phytoconstituents from a classical Siddha-based poly-herbal formulation called Swasa Kudori Tablet to treat asthma. The phytoconstituents of Swasa Kudori are identified as Calotropis gigantea, Piper nigrum, and (Co-drug) Abies webbiana. Active chemical compounds are extracted with the Chemical Entities of Biological Interest (ChEBI) database. The gene targets of each compound are identified based on the pharmacological activity using the DIGEP-Pred database. Thirty-two genes showing Pa> 0.7 is screened, and the target markers are selected after performing gene overlap evaluation with the asthma genes reported in GeneCards and DisGeNET database. Ten markers are identified, such as ADIPOQ, CASP8, CAT, CCL2, CD86, FKBP5, HMOX1, NFE2L2, TIMP1, VDR, in common, listed as molecular targets. Pharmacokinetic assessment (ADME) revealed five natural drug compounds 2-5-7-trihydroxy-2-(4-hydroxyphenyl)-2,3-dihydro-4H-chromen-4-one, (+)-catechin-3'-methyl ether, futoenone, 5-hydroxy-4',7-dimethoxyflavanone, and pinocembrin showing better druggability. Further screening delineates the target (HMOX1) and drug (pinocembrin) for molecular docking evaluation. When docked with HO-1, Pinocembrin showed a binding affinity of -8.0 kcal/mol. MD simulation studies substantiate the docking studies as HO-1 in complex with pinocembrin remains stable in the simulated trajectory. The current findings exhibit the significance of traditional medicines as potential drug candidates against asthma.

Genomic insights and advanced machine learning: characterizing autism spectrum disorder biomarkers and genetic interactions.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by altered brain connectivity and function. In this study, we employed advanced bioinformatics and explainable AI to analyze gene expression associated with ASD, using data from five GEO datasets. Among 351 neurotypical controls and 358 individuals with autism, we identified 3,339 Differentially Expressed Genes (DEGs) with an adjusted p-value (≤ 0.05). A subsequent meta-analysis pinpointed 342 DEGs (adjusted p-value ≤ 0.001), including 19 upregulated and 10 down-regulated genes across all datasets. Shared genes, pathogenic single nucleotide polymorphisms (SNPs), chromosomal positions, and their impact on biological pathways were examined. We identified potential biomarkers (HOXB3, NR2F2, MAPK8IP3, PIGT, SEMA4D, and SSH1) through text mining, meriting further investigation. Additionally, we shed light on the roles of RPS4Y1 and KDM5D genes in neurogenesis and neurodevelopment. Our analysis detected 1,286 SNPs linked to ASD-related conditions, of which 14 high-risk SNPs were located on chromosomes 10 and X. We highlighted potential missense SNPs associated with FGFR inhibitors, suggesting that it may serve as a promising biomarker for responsiveness to targeted therapies. Our explainable AI model identified the MID2 gene as a potential ASD biomarker. This research unveils vital genes and potential biomarkers, providing a foundation for novel gene discovery in complex diseases.

3D CoMoO4 nanoflake arrays decorated disposable pencil graphite electrode for selective and sensitive enzyme-less electrochemical glucose sensors.

Three-dimensional (3D) cobalt molybdate (CoMoO4) hierarchical nanoflake arrays on pencil graphite electrode (PGE) (CoMoO4/PGE) are actualized via one-pot hydrothermal technique. The morphological features comprehend that the CoMoO4 nanoflake arrays expose the 3D, open, porous, and interconnected network architectures on PGE. The formation and growth mechanisms of CoMoO4 nanostructures on PGE are supported with different structural and morphological characterizations. The constructed CoMoO4/PGE is operated as an electrocatalytic probe in enzyme-less electrochemical glucose sensor (ELEGS), confronting the impairments of cost- and time-obsessed conventional electrode polishing and catalyst amendment progressions and obliged the employment of a non-conducting binder. The wide-opened interior and exterior architectures of CoMoO4 nanoflake arrays escalate the glucose utilization efficacy, whilst the intertwined nanoflakes and graphitic carbon layers, respectively, of CoMoO4 and PGE articulate the continual electron mobility and catalytically active channels of CoMoO4/PGE. It jointly escalates the ELEGS concerts of CoMoO4/PGE including high sensitivity (1613 µA mM-1 cm-2), wide linear glucose range (0.0003-10 mM), and low detection limit (0.12 µM) at a working potential of 0.65 V (vs. Ag/AgCl) together with the good recovery in human serum. Thus, the fabricated CoMoO4/PGE extends exclusive virtues of modest electrode production, virtuous affinity, swift response, and excellent sensitivity and selectivity, exposing innovative prospects to reconnoitring the economically viable ELEGSs with binder-free, affordable cost, and expansible 3D electrocatalytic probes.

Graphene overcoats for ultra-high storage density magnetic media.

Hard disk drives (HDDs) are used as secondary storage in digital electronic devices owing to low cost and large data storage capacity. Due to the exponentially increasing amount of data, there is a need to increase areal storage densities beyond ~1 Tb/in2. This requires the thickness of carbon overcoats (COCs) to be <2 nm. However, friction, wear, corrosion, and thermal stability are critical concerns below 2 nm, limiting current technology, and restricting COC integration with heat assisted magnetic recording technology (HAMR). Here we show that graphene-based overcoats can overcome all these limitations, and achieve two-fold reduction in friction and provide better corrosion and wear resistance than state-of-the-art COCs, while withstanding HAMR conditions. Thus, we expect that graphene overcoats may enable the development of 4-10 Tb/in2 areal density HDDs when employing suitable recording technologies, such as HAMR and HAMR+bit patterned media.

Clinico-microbiological Profile of Septic Diabetic Foot with Special Reference to Anaerobic Infection.

Introduction Diabetic foot infections are a major cause of non-traumatic amputations. The role of anaerobes in the prognosis of these infections is particularly unclear. This study was conducted with the aim of correlating microbiological profiles with clinical outcomes in these diabetic foot ulcer patients. Methodology This prospective observational study was done in a tertiary care centre in South India. All patients admitted with diabetic foot ulcers for two years were included in the study. Tissue biopsies were collected from the ulcer for aerobic and anaerobic cultures. The patients were grouped as those with aerobic infection alone (anaerobe negative) and those with mixed aerobic and anaerobic infections (anaerobe positive). Anaerobic culture was performed using the Robertson cooked meat (RCM) medium. The ulcer of the foot was described with respect to site, size, duration, history of previous amputation(s), and history of number and class of antibiotic intake prior to hospitalization. Clinical course and Wagner's grades of the diabetic foot ulcers were compared for aerobic and anaerobic infections. Results A total of 104 patients were included in the study. There were no significant differences between the two groups with regards to duration of diabetes, random blood sugar (RBS) at the time of admission, compliance to drugs, and mode of blood sugar control and prior intake of antibiotics. Patients with anaerobic infections were found to have a higher incidence of fever in this study (38.1% vs. 14.5%; p = 0.0057), as compared to patients with aerobic infections. More than half of the patients in the anaerobic infection group presented with Wagner's grade IV and above, as compared to the aerobic infection group (59.5% vs. 32.2%; p = 0.0059), which was statistically significant. Patients with anaerobic infections also had high numbers of major and minor amputations when compared to patients with aerobic infections. Conclusion Septic diabetic foot patients with fever at the time of admission and a high Wagner's grade have a greater chance of harbouring anaerobic infections. Drugs for anaerobic coverage should be considered for wounds beyond Wagner's grade III. Anaerobic infections resulted in increased risk of morbidity in diabetic foot ulcer patients but did not have any influence on mortality.

Axial Torsion of Gangrenous Meckel's Diverticulum Causing Small Bowel Obstruction.

Meckel's diverticulum (MD) is a commonly encountered congenital anomaly of the small intestine. We report an extremely unusual case of an axially torted, gangrenous MD presenting as acute intestinal obstruction. A 26-year-old male patient presented to our emergency department with 3 days history of abdominal pain, distention and bilious vomiting. On laparotomy, there was minimal hemorrhagic fluid localized in right iliac fossa and small bowel loops were dilated. A MD was seen attached to the mesentery of nonadjacent small bowel by a peritoneal band. The diverticulum was axially torted and gangrenous. In addition, there was compression of ileum by the peritoneal band resulting in intestinal obstruction, which was relieved on dividing the band. Resection and anastomosis of the small bowel including the MD was performed. We hereby report a rare and unusual complication of a MD. Although treatment outcome is generally good, pre-operative diagnosis is often difficult.

Generic antibiotic industries: Challenges and implied strategies with regulatory perspectives.

Ever since the discovery of antibiotics, the quality of human life greatly improved in the 20(th) century. The discovery of penicillin transformed the medicine industry and initiated a search for a better antibiotic every time resulting in several synthetic and semi-synthetic antibiotics. Beginning with the 1937 sulfa drug tragedy, the drug regulations had a parallel growth along with the antibiotics and the antibiotic-based generic Pharma industries. This review article is focused on the scenario depicting current global Pharma industries based on generic antibiotics. Several regulatory aspects involved with these industries have been discussed along with the complexity of the market, issues that could affect their growth, their struggle for quality, and their compliance with the tightened regulations. With the skyrocketing commercialization of antibiotics through generics and the leveraging technologic renaissance, generic industries are involved in providing maximum safer benefits for the welfare of the people, highlighting its need today..