Ru(II) Complexes with Protic- and Anionic-Naked-NHC Ligands for Cooperative Activation of Small Molecules.

A set of ruthenium(II)-protic-N-heterocyclic carbene complexes, [Ru(NNCH )(PPh3 )2 (X)]Cl (1, X=Cl and 2, X=H) and their deprotonated forms [Ru(NNC)(PPh3 )2 (X)] (1', X=Cl and 2', X=H), in which NNC is a new unsymmetrical pincer ligand, are reported. The four complexes are interconvertible by simple acid-base chemistry. The combined theoretical and spectroscopic investigations indicate charge segregation in anionic-NHC complexes (1' and 2') and can be described from a Lewis pair perspective. The chemical reactivity of deprotonated complex 1' shows cooperative small molecule activation. Complex 1' activates H-H bond of hydrogen, C(sp3 )-I bond of iodomethane, and C(sp)-H bond of phenylacetylene. The activation of CO2 using anionic NHC complex 1' at moderate temperature and ambient pressure and subsequent conversion to formate is also described. All the new compounds have been characterized using ESI-MS, 1 H, 13 C, and 31 P NMR spectroscopy. Molecular structures of 1, 2, and 2' have also been determined with single-crystal X-ray diffraction. The cooperative small molecule activation perspective broadens the scope of potential applications of anionic-NHC complexes in small molecule activation, including the conversion of carbon dioxide to formate, a much sought after reaction in the renewable energy and sustainable development domains.

Biofabricated zinc oxide nanoparticles impair cognitive function via modulating oxidative stress and acetylcholinesterase level in mice.

Current work was designed to explore the effect of ZnO nanoparticles (ZnONP) biofabricated by using Trianthema portulacastrum (TP) leaves extract on mice brain hippocampus. ZnO nanoparticles of TP leaves (ZnOTP) were synthesized by co-precipitation method and further characterized by using various techniques such as UV-Vis spectrophotometer, Field Emission Scanning Electron Microscopy (FESEM), Fourier Transform Infrared (FTIR), and Energy Dispersive X-ray (EDX). ZnOTP were evaluated for in vitro antioxidant activity, in vivo behavior models (for assessment of cognitive ability), acetylcholinesterase (AChE) activity along with other neurotransmitters content determination, estimation of various oxidative stress parameters and analysis of zinc content in the brain as well as plasma. Histopathological evaluation of the brain hippocampus of each group was performed to corroborate the statistical results. Spherical ZnOTP of 10 to 20 nm size embedded with different phytoconstituents of TP was confirmed. Results of our study revealed a significant memory deficit in mice treated with ZnOTP. Neuronal degeneration was also observed via a significant increase in AChE activity and oxidative stress levels in the brain of mice administered with ZnOTP. Exposure of ZnOTP was also found responsible for modulation of neurotransmission in hippocampus area. Further, ZnOTP disturbed the zinc homeostasis in hippocampus via elevation of zinc content in brain as well as plasma. Histopathology of hippocampus supported the damaging impact of ZnOTP by an increase in vacuolated cytoplasm and focal gliosis in groups treated with ZnOTP. Results demonstrated the neurotoxic effect of ZnOTP on brain hippocampus via cognitive impairment by alteration of neurotransmitter level, zinc content and oxidative stress.

Molecular Docking and Cognitive Impairment Attenuating Effect of Phenolic Compound Rich Fraction of Trianthema portulacastrum in Scopolamine Induced Alzheimer's Disease Like Condition.

Dementia is considered as the frequent cause of neurodegenerative mental disorder such as Alzheimer's disease (AD) amongst elderly people. Free radicals as well as cholinergic deficit neurons within nucleus basalis magnocellularis demonstrated to attribute with aggregation of ß amyloid which further acts as an essential hallmark in AD. Various phenolic phytoconstituents exists in Trianthema portulastrum (TP) leaves have been reported as active against various neurological disorders. The current investigation was undertaken to evaluate the antiamnesic potential of butanol fraction of TP hydroethanolic extract (BFTP) by utilizing rodent models of elevated plus maze (EPM) and Hebbs William Maze (HWM) along with in vitro and in vivo antioxidant as well as acetylcholinesterase (AChE) inhibition studies. Molecular docking studies were also performed for evaluation of molecular interaction of existed phenolic compounds in BFTP. In vitro antioxidant study revealed concentration dependant strong ability of BFTP to inhibit free radicals. In vitro AChE inhibition study showed competitive type of inhibition kinetics. BFTP significantly reversed (p < 0.005 versus scopolamine) the damaging effect of scopolamine by reducing TL (Transfer Latency) and TRC (Time taken to recognize the reward chamber) in the EPM and HWM, respectively. BFTP also contributed towards increased (p < 0.005 versus scopolamine) enzymatic antioxidant as well as hippocampal acetylcholine (ACh) levels. Histological studies also supported the results as BFTP pretreated mice significantly reversed the scopolamine induced histological changes in hippocampal region. Docking studies confirmed chlorogenic acid has the most significant binding affinity towards AChE. This research finding concludes that BFTP could be a beneficial agent for management of cognition and behavioral disorders associated with AD.

Phytofabricated silver nanoparticles of Phyllanthus emblica attenuated diethylnitrosamine-induced hepatic cancer via knock-down oxidative stress and inflammation.

Oxidative stress and inflammation play a pivotal role in the expansion and progression of hepatic cancer. Nanoparticle-based drug delivery can quickly enhance the restorative capability of hepatic cancer. Silver nanoparticles synthesized from plant source are of great importance due to their small size, economic, non-hazardous and different biomedical applications. In the current study, we have evaluated the impacts of oxidative stress and proinflammatory markers of biosynthesized silver nanoparticles of Phyllanthus emblica (PE) leaves against diethylnitrosamine-induced hepatocellular carcinoma (HCC) in wistar rats till 16 weeks with its underlying mechanism. The physico-chemical properties of biosynthesized silver nanoparticles were determined by ultra-visible spectroscopy, Fourier transform infrared spectroscopy, field emission scanning electron microscope, energy dispersive X-ray analysis, transmission electron microscopy and X-ray diffraction studies. Biofabricated silver nanoparticles (PEAgNPs) significantly enhanced the process of recovery from hepatic cancer in animal models, which was ascertained by increased body weight, reduced hepatic knobs on the outer surface of liver, downregulated serum biochemical parameters (ALT: 134.66 ± 2.60; AST: 120.33 ± 3.18; ALP: 153.33 ± 4.25; AFP: 167.33 ± 3.38), decreased hepatic lipid peroxidation (20.22 ± 1.74), increased membrane-bound enzymes (Na+/K+ATPase: 4.18 ± 0.20; Ca2+ATPase: 6.24 ± 0.12), increased antioxidants parameters (CAT: 64.89 ± 4.13; SOD: 6.01 ± 0.11; GPx: 8.55 ± 0.05), alteration in the level of proinflammatory cytokines (TNF-α: 90.15 ± 5.77; NF-κB: 173.29 ± 7.26; IL-6: 178.11 ± 3.16; IL-1ß: 48.26 ± 1.89) and histopathological studies. Our outcomes implicate successfully biofabrication of silver nanoparticles and exhibited a chemoprotective potential in the prevention and intervention of hepatocellular carcinoma.

Development, characterization, and pharmacodynamic evaluation of hydrochlorothiazide loaded self-nanoemulsifying drug delivery systems.

The objective of the current work was to develop optimized self-nanoemulsifying drug delivery systems (SNEDDS) and evaluate their in vitro and in vivo performance. The research comprised various studies which includes solubility studies in various vehicles, pseudoternary phase diagram construction, and preparation and characterization of SNEDDS along with in vitro dissolution and in vivo pharmacodynamic profiling. Based on dissolution profile, a remarkable increase in rate of dissolution was observed in comparison with plain drug and marketed formulation. Optimized SNEDDS formulation was composed of Capmul MCM (19.17% w/w), Tween 80 (57.5% w/w), Transcutol P (12.7% w/w), and HCT (4.17% w/w). In vivo pharmacodynamic evaluation in Wistar rats showed considerable increase in pharmacological effect of HCT by SNEDDS formulation as compared with plain HCT.

Percentage of patients shifting to another treatment modality: An experience-guided decision.

OBJECTIVE: This study aimed to assess the frequency with which orthodontic patients decided to shift to another type of orthodontic appliance, among conventional metal brackets, ceramic brackets, lingual brackets and clear aligner, based on their personal experiences of pain, ulcers, bad breath, hygiene issues and social difficulties. MATERIAL AND METHODS: This study comprises of patients seeking orthodontic treatment. The sample (n = 500; age group = 19-25 years) was divided equally into four groups based on the treatment modality: conventional metal brackets, ceramic brackets, lingual brackets and clear aligner. Patients rated the questionnaire using a visual analogue scale, to assess variables (such as pain, ulcer etc) that impact various treatment modalities. Subsequently, patients from all groups provided feedback regarding their treatment experiences, and expressed their preference for an alternative modality. Intergroup comparison among the four groups was done using one-way analysis of variance with Tukey's HSD post-hoc test (p ≤ 0.05). RESULTS: Patients who received lingual brackets reported higher levels of pain and ulceration, as compared to those who received clear aligners. All four groups showed statistically significant differences for ulcers during treatment (p ≤ 0.05). Of the 125 patients who received conventional metal brackets, 28% expressed a preference for clear aligner therapy, while 20% preferred ceramic brackets. In the lingual group, 56% of 125 patients preferred clear aligner therapy, and 8% preferred ceramic brackets to complete their treatment. In the ceramic group, 83% did not want to switch, whereas 17% desired to switch to clear aligner, while in aligner group no patient desired to switch. CONCLUSIONS: A higher percentage of patients from lingual brackets group chose to shift to clear aligners, followed by conventional metal brackets group and by ceramic brackets group, in this descending order. The clear aligner group demonstrated fewer issues than the other treatment modalities.

Exploring the Potential of Herbal Compounds as Autophagy Modulators in Alzheimer's Disease: A Comprehensive Review.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that causes atrophy of brain cells, leading to their death, and has become a leading cause of death in aging populations worldwide. AD is characterized by ß-amyloid (Aß) deposition and tau phosphorylation in neural tissues, but the precise pathophysiology of the disease is still obscure. Autophagy is an evolutionarily targeted mechanism that is necessary for the elimination of neuronal and glial misfolded proteins as well as proteins. It also plays an essential role in synaptic plasticity. The aberrant autophagy primarily influences the process of aging and neurodegeneration. Autophagy significantly influences how Aß and tau function physiologically, therefore, atypical autophagy is expected to perform an important role in Aß deposition and tau phosphorylation characteristic in the development of AD. Bioactive phytoconstituents could majorly contribute as a natural yet effective alternative approach to slow down the progression of neurodegeneration and promote the active aging process in elderly patients. Over the recent years, it is well evidenced that different secondary metabolites including polyphenols, alkaloids, terpenes, and phenols exhibited neuroprotective effects, and attenuated brain damage, and cognitive impairment in vitro as well as in vivo. Additionally, the underlying mechanism of action shared by them is the regulation of competent autophagy via the removal of aggregated protein and mitochondrial dysfunction. The present article is structured as a reference for researchers keen to investigate and assess the new natural compound-mediated therapeutic approach for AD treatment through the modulation of autophagy.

Combatting Antibiotic Resistance: Identifying Gaps in Knowledge, Attitude, and Practice Among Medical Interns.

INTRODUCTION: Antibiotic resistance presents a significant global health threat to modern medicine. The awareness and attitude of future doctors undergoing training may play a crucial role in addressing this important issue, influencing the control of resistance and promoting responsible antibiotic stewardship. This study aimed to estimate knowledge, attitudes, and practices regarding antibiotic usage and antimicrobial resistance among tertiary care teaching hospital medical interns. METHODOLOGY: The questionnaire-based cross-sectional study was conducted on 123 MBBS interns from multiple medical institutions. Intern's knowledge, attitudes, and self-reported practices regarding antibiotic use were recorded. RESULTS: Based on survey responses from 123 participants, 116 (94.31%) were aware of the adverse effects of indiscriminate antibiotic use, recognizing the risks of ineffective treatment, increased adverse effects, prolonged illness, bacterial resistance, and higher medical costs. Most (106, 86.18%) acknowledged the challenges of treating antibiotic-resistant infections, and 69 (56.10%) correctly identified that bacteria are not a cause of the common cold and flu. Most (115, 93.5%) recognized antibiotic resistance as a significant global health problem. In attitude, 90 (73%) believed antibiotics should be avoided for colds, but 80 (65%) thought they hastened fever recovery. Only 48 (39%) recognized that antibiotics contribute to resistance, while 102 (83%) agreed skipping doses fosters resistance. Most support hospital policies (118, 96%) and curriculum courses (112, 91%) for rational antibiotic use. Regarding practice, 12 (9.76%) interns admitted to overusing antibiotics, 68 (55.28%) consulted a doctor before starting antibiotics, and 87 (70.73%) checked expiry dates. Additionally, 62 (50.41%) preferred antibiotics for cough and sore throat symptoms. CONCLUSIONS: The study highlights that while interns have a good knowledge and awareness of the harms of antibiotic misuse, they are not translating this knowledge into practice. This indicates a disconnect between understanding and application. Therefore, there is a need to add a rational antibiotic prescription and stewardship module to the medical curriculum to ensure that knowledge is effectively translated into changing beliefs and practices.

Intrinsically dominated anomalous Hall effect in pulsed laser deposited epitaxial Co2MnGe ferromagnetic full Heusler alloy thin films.

Large size epitaxial thin films of ferromagnetic Co2MnGe full Heusler alloy are grown over MgO(100) substrate by using pulsed laser deposition technique under optimized growth conditions. Metallic behavior is confirmed from the longitudinal resistivity-temperature data, while a minimum in the resistivity at ∼25 K is attributed to the disorder-induced weak localization effect. Importantly, a dominating intrinsic anomalous Hall conductivity value of ∼21 S cm-1 against an overall anomalous Hall conductivity value of ∼36 S cm-1 at the room temperature has been estimated for the epitaxial Co2MnGe film. The dominating intrinsic mechanism is also evident from the near temperature-independent behavior of the overall anomalous Hall conductivity.

Investigation of the influential factors for hepatic osteodystrophy in chronic liver disease: A case-control survey among the patients attending a tertiary care hospital in a rural region of Northern India.

Objectives: Hepatic osteodystrophy (HOD) is a well-recognized complication of chronic liver diseases (CLD), but the influential factors associated with this complication were studied scarcely in a rural Indian population. The study aims to evaluate the prevalence of HOD and variables that might influence it among cases diagnosed with CLD. Materials and Methods: It is a cross-sectional observational design survey that was performed in a hospital among the two-hundred cases and controls with a 1:1 ratio who were age (>18 years) and gender matched in a period between April and October 2021. They were subjected to etiological workup, hematological and biochemical investigations, and Vitamin D levels. Then, dual-energy X-ray absorptiometry was used to measure the bone mineral densitometry (BMD) for whole-body, lumbar spine (LS), and hip. HOD was diagnosed according to the WHO criteria. Then, the Chi-square test and conditional logistic regression analysis were used to investigate the influential factors of HOD in CLD patients. Results: The whole-body, LS-spine, and hip BMDs in CLD cases were found to be significantly lower as compared to controls. When the participants among both groups were stratified by age and gender, a significant difference in LS-spine and hip BMD was observed in elderly patients (>60 years), and in both the male and female patients. HOD was found in 70% of CLD patients. After multivariate analysis in CLD patients, we identified that being a male patient (odds ratio [OR] = 3.03), older age (OR = 3.54), duration of illness for more than 5 years (OR = 3.89), decompensated liver dysfunction with Child-Turcotte-Pugh-B and C grading (OR = 8.28), and low level of Vitamin D (OR = 18.45) were the risk factors for HOD. Conclusion: This study concludes that severity of illness and lower level of Vitamin D were the main influential factors for HOD. Supplementation of Vitamin D and calcium in the patients can abate the risk of fractures in our rural communities.