TEX13B is essential for metabolic reprogramming during germ cell differentiation.

STUDY QUESTION: What is the functional significance of Tex13b in male germ cell development and differentiation? SUMMARY ANSWER: Tex13b regulates male germ cell differentiation by metabolic reprogramming during spermatogenesis. WHAT IS KNOWN ALREADY: Studies in mice and humans suggest that TEX13B is a transcription factor and is exclusively expressed in germ cells. STUDY DESIGN, SIZE, DURATION: We sequenced the coding regions of TEX13B in 628 infertile men and 427 ethnically matched fertile control men. Further, to identify the molecular function of Tex13b, we created a Tex13b knockout and conditional overexpression system in GC-1spg (hereafter, GC-1) cells. PARTICIPANTS/MATERIALS, SETTING, METHODS: Our recent exome sequencing study identified novel candidate genes for male infertility. TEX13B was found to be one of the potential candidates, hence we explored the role of TEX13B in male infertility within a large infertile case-control cohort. We performed functional analyses of Tex13b in a GC-1 cell line using CRISPR-Cas9. We differentially labelled the cell proteins by stable isotope labelling of amino acids in cell culture (SILAC) and performed mass spectrometry-based whole-cell proteomics to identify the differential protein regulation in knockout cells compared to wild-type cells. We found that Tex13b knockout leads to downregulation of the OXPHOS complexes and upregulation of glycolysis genes, which was further validated by western blotting. These results were further confirmed by respirometry analysis in Tex13b knockout cells. Further, we also performed a conditional overexpression of TEX13B in GC-1 cells and studied the expression of OXPHOS complex proteins by western blotting. MAIN RESULTS AND THE ROLE OF CHANCE: We identified a rare variant, rs775429506 (p.Gly237Glu), exclusively in two non-obstructive-azoospermia (NOA) men, that may genetically predispose these men for infertility. Further, we demonstrated that Tex13b functions in the transcription regulation of OXPHOS complexes. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: We examined the function of Tex13b in GC-1 in vitro by knocking out and conditional overexpression, for understanding the function of Tex13b in germ cells. Unfortunately, this could not be replicated in either an animal model or in patient-derived tissue due to the non-availability of an animal model or patient's testis biopsies. WIDER IMPLICATIONS OF THE FINDINGS: This study identified that Tex13b plays an important role in male germ cell development and differentiation. The findings of this study would be useful for screening infertile males with spermatogenic failure and counselling them before the implementation of assisted reproduction technique(s). STUDY FUNDING/COMPETING INTEREST(S): Funding was provided by the Council of Scientific and Industrial Research (CSIR) under the network project (BSC0101 and MLP0113) and SERB, the Department of Science and Technology, Government of India (J C Bose Fellowship: JCB/2019/000027). The authors do not have any competing interest.

In vitro and in silico investigation of glycyrrhizic acid encapsulated zein nanoparticles: A synergistic targeted drug delivery approach for breast cancer.

This study presents an innovative approach for targeted drug delivery through the development of Glycyrrhizic acid-loaded zein nanoparticles (GA-LNPs) as a proficient carrier system. The juxtaposition of zein, a hydrophobic biological macromolecule as a protein carrier, and Glycyrrhizic acid (GA), a hydrophilic therapeutic compound, exemplifies the adaptability of hydrocolloids within cutting-edge drug delivery systems. The characterization and functional traits of research encompass multifaceted analyses of natural macromolecules, which elucidate the homogeneous and spherical morphology of GA-LNPs with an average size of 170.49 nm. The controlled drug release profile of GA, orchestrated under simulated gastrointestinal conditions, adheres to diffusion-based Higuchi kinetics, reflecting the controlled release of the natural macromolecules. The intermolecular interactions among Zein, GA, and cross-linker EDC, facilitated through molecular dynamics simulations, fortify the structural integrity of the encapsulation matrix. In Vitro studies revealed enhanced cellular uptake of GA-LNPs in MCF-7 breast cancer cells. This cellular internalization was further confirmed through cytotoxicity assessments using MTT and apoptosis assays (fluorescence microscopy), which demonstrated the prominent anticancer effects of GA-LNPs on MCF-7 in time/dose-dependent manner. The successful formulation of GA-LNPs, coupled with their sustained release and potent anticancer properties, makes them a potential platform for advanced targeted therapeutic strategies in biomedical applications.

Soil-mustard revitalization via rice husk ash, a promising soil amendment material for sustainable management of heavy metal contamination in tropical ecosystem.

Prolonged wastewater irrigation in agriculture has led to the accumulation of heavy metals in soil, endangering both the soil quality and food safety, thereby posing a potential threat to human health through the consumption of contaminated crops. The present study aimed to enhance the yield of mustard (Brassica juncea L. cv. Varuna and NRCHB 101) plants and stabilize heavy metals (Cd, Cr, Ni, Cu, and Zn) in wastewater-irrigated soil using rice husk ash (RHA), rice mill by-product, collected from Chandauli region of Eastern Uttar Pradesh, India. Results demonstrated significant improvements in growth, biomass, physiology, and yield of mustard plant with increasing RHA application in wastewater irrigated soil (p ≤ 0.05). Heavy metal accumulation in different parts of mustard plants decreased as RHA application rate increased. Applying RHA at 2% in soil proved to be most effective in reducing Cd, Cr, Ni, Cu, and Zn accumulation in seeds by 29%, 29.6%, 23.1%, 21.3% and 20.1%, respectively in Varuna and 30.1%, 21.4%, 11.1%, 12.1%, and 28.5%, respectively in NRCHB 101cultivars. The present findings showed that RHA amendment in wastewater irrigated soil had reduced bioaccumulation of Cd, Cr, Ni, Cu, and Zn and consequently their toxicity in cultivated mustard plants. A novel application of RHA is unveiled in this research, offering a promising solution to promote sustainable agriculture and to reduce heavy metal associated health risks within the soil-mustard system.

Truncated variants of thyroid hormone receptor beta display disease-inflicting malfunctioning at cellular level.

Thyroid hormone receptor ß (THRß) is a member of the nuclear receptor superfamily of ligand-modulated transcription factors. Upon ligand binding, THRß sequentially recruits the components of transcriptional machinery to modulate target gene expression. In addition to regulating diverse physiological processes, THRß plays a crucial role in hypothalamus-pituitary-thyroid axis feedback regulation. Anomalies in THRß gene/protein structure are associated with onset of diverse disease states. In this study, we investigated disease-inflicting truncated variants of THRß using in-silico analysis and cell-based assays. We examined the THRß truncated variants on multiple test parameters, including subcellular localization, ligand-receptor interactions, transcriptional functions, interaction with heterodimeric partner RXR, and receptor-chromatin interactions. Moreover, molecular dynamic simulation approaches predicted that shortened THRß-LBD due to point mutations contributes proportionally to the loss of structural integrity and receptor stability. Deviant subcellular localization and compromised transcriptional function were apparent with these truncated variants. Present study shows that 'mitotic bookmarking' property of some THRß variants is also affected. The study highlights that structural and conformational attributes of THRß are necessary for normal receptor functioning, and any deviations may contribute to the underlying cause of the inflicted diseases. We anticipate that insights derived herein may contribute to improved mechanistic understanding to assess disease predisposition.

Buccal versus buccal palatal infiltration for pulpal anesthesia using 2% lidocaine and 4% articaine: A randomized controlled trial.

Background: The inability in achieving complete pulpal anesthesia with standard buccal infiltration especially in cases with SIP used for maxillary teeth. The study aimed to compare the anesthetic efficacy of buccal and buccal plus palatal infiltration technique using 2% lidocaine and 4% articaine in permanent maxillary first molars with the diagnosis of symptomatic irreversible pulpitis (SIP). Material and method: One hundred and twenty-three patients with clinical diagnosis of SIP, aged 18-50 years were randomly allocated to three treatment groups (N = 41). Group 1(BIL): Buccal infiltration technique using 2% lidocaine with 1:80,000 adrenaline. Group 2(BPIL): combination of buccal plus palatal infiltration using 2% Lidocaine with 1:80,000 adrenaline. Group 3(BIA): Buccal infiltration using 4% articaine with 1:100,000 adrenaline. Pain intensity of patients were recorded before and after the administration of local anesthesia during endodontic procedure that is during caries removal, access preparation and pulp removal using Heft-Parker Visual Analog Scale (HP-VAS). Success was defined by "no pain (0 mm)" or "mild pain (0-54 mm)" during endodontic procedure. The anesthetic efficacy rates were analyzed using chi-square tests, age differences using one-way ANOVA. Results: The final analysis included total of 117 patients. Higher success was observed in group II (85%) in comparison to group I (69%) and group III (74%), but the difference was statistically nonsignificant (p > 0.05). Our results demonstrated a nonsignificant difference between genders in all three groups (p > 0.05). Conclusion: The use of buccal plus palatal infiltration and 4% articaine can provide effective anesthesia as standard buccal infiltration and 2% lidocaine for patients with SIP in maxillary first molars.

Folate conjugated albumin as a targeted nanocarrier for the delivery of fisetin: in silico and in vitro biological studies.

Fisetin (FST), a natural flavonoid compound derived from various fruits and vegetables, including apple, strawberry, and onion, demonstrates potential for a wide range of pharmaceutical applications, including potential anticancer properties. However, challenges such as low bioavailability, poor aqueous solubility, and limited permeability restrict the use of FST in the pharmaceutical sector. Nowadays, targeted nanomedicines have garnered attention to overcome limitations associated with phytochemicals, including FST. In the present study, we have designed and successfully prepared folate-targeted FST nanoparticles (FFNPs). Characterization through DLS and FE-SEM revealed the successful preparation of monodisperse (PDI: 0.117), nanoscale-sized (150 nm), and spherical nanoparticles. Physicochemical characterization including FTIR, XRD, DSC, and TGA analysis, confirmed the encapsulation of the FST within the Folic acid (FA) - conjugated nanoparticles (CNPs) and revealed its amorphous nature. Molecular docking analysis revealed the strong binding affinity and specific amino acid interactions involved in the BSA-FST-FA complex, suggesting the potential synergistic effect of FST and FA in enhancing the therapeutic activity of the FFANPs. Cytotoxic assessments by the MTT assay, migration assay, AO-EtBr staining assay, colony formation assay, and cellular uptake study demonstrated enhanced anticancer efficacy, apoptosis induction, and enhanced uptake of FFNPs compared to pure FST. These findings propose prepared FFNPs as a promising targeted drug delivery nanocarrier for effective FST delivery in cancer therapy.

Phytoformulation with hydroxycitric acid and capsaicin protects against high-fat-diet-induced obesity cardiomyopathy by reducing cardiac lipid deposition and ameliorating inflammation and apoptosis in the heart.

Background and aim: Phytoformulation therapy is a pioneering strategy for the treatment of metabolic disorders and related diseases. The aim of the present study was to investigate the protective effect of a phytoformulation consisting of hydroxycitric acid and capsaicin against obesity-related cardiomyopathy. Experimental procedure: Sprague-Dawley rats were fed HFD for 21 weeks, and phytoformulation (100 mg/kg body weight) was administered orally for 45 days starting at week 16. Results and conclusion: We found that HFD supplementation resulted in significant hyperglycemia and caused an increase in cardiac lipid deposition, inflammation and apoptosis in the heart. Phytoformulation therapy not only significantly decreased blood levels of glucose, cholesterol, triglycerides, free fatty acids, and inflammatory cytokines in obese rats, but also protected cardiac tissue, as shown by histological analysis. Conversely, phytoformulation therapy decreased mRNA levels for sterol regulatory element-binding factor 1, fatty acid synthase, acetyl-CoA carboxylase, and fatty acid binding protein 1 genes involved in fatty acid synthesis and absorption in obese rats. It increased the levels of lysosomal acid lipase, hormone-sensitive lipase, and lipoprotein lipase genes involved in fatty acid degradation in the heart. In addition, the phytoformulation improved cardiac inflammation and apoptosis by downregulating the genes nuclear factor kappa-light-chain enhancer of activated B cells (NF-kB), tumour necrosis factor α, interleukin-6, toll-like receptor-4 (TLR-4), BCL2-associated X and caspase-3. In conclusion, our results show that the phytoformulation improved insulin sensitivity and attenuated myocardial lipid accumulation, inflammation, and apoptosis in the heart of HFD-induced obese rats by regulating fatty acid metabolism genes and downregulating NF-kB/TLR-4/caspase-3.

Synthesis, physiochemical characterization, molecular docking study, and anti-breast cancer activity of silymarin loaded zein nanoparticles.

Breast cancer is a major cause of death in women worldwide leading to requirement of new therapeutic strategies. Silymarin demonstrated the anti-cancer activity however, due to low bioavailability its use is restricted. This study aimed to improve the solubility of silymarin by developing a silymarin loaded zein nanoparticles (SLNPs) which was stabilized by beta cyclodextrin. Comprehensive physiochemical characterization studies based on DLS, FTIR, UV-Vis Spectroscopy, FE-SEM, TEM, XRD, DSC, NMR and TGA confirmed the successful synthesis of SLNPs via an anti-solvent precipitation method. FE-SEM and TEM images demonstrated the uniform size and spherical shape of nanoparticles with encapsulation and loading efficiencies of 84.32 ± 1.9 % and 15.25 ± 2.4 % respectively. The zein protein interaction with silymarin, and ß-cyclodextrin was shown to be beneficial via the use of molecular simulations and binding energy calculations. Cellular studies demonstrated dose and time dependent cytotoxicity of SLNPs on MCF-7 breast cancer cell. FACS, qRT-PCR and Western blotting showed Bax (pro-apoptotic) upregulation while Bcl-2 (anti-apoptotic) downregulation. Our findings suggest that these loaded nanoparticles are more efficient than pure drug, enhancing its bioavailability and paving the path for developing it as a promising nutraceutical to treat breast cancer.

Cr- and Ga-Modified ZSM-5 Catalyst for the Production of Renewable BTX from Bioethanol.

Light aromatics (benzene, toluene, and xylene, collectively known as BTX) are essential commodity chemicals in the petrochemical industry. The present study examines the aromatization of bioethanol with Cr- and Ga-modified ZSM-5. Both Cr and Ga were incorporated by the ion-exchange method. Cr-modified ZSM-5 outperforms the Ga-modified ZSM-5 and H-ZSM-5 catalysts. Cr-H-ZSM-5 almost doubled the carbon yield of aromatics compared to H-ZSM-5 at an optimum reaction temperature of 450 °C. Cr-H-ZSM-5 produced aromatics with a yield of ~40 %. The effect of dilution in feed on BTX production is also studied. Cr-H-ZSM-5 was found to be more active than H-ZSM-5. Complete ethanol conversion was obtained with both pure and dilute bioethanol. The Bronsted-Lewis acid (BLA) pair formed after metal incorporation is responsible for dehydrogenation followed by aromatization, leading to increased aromatic production.

Screening of mustard cultivars for phytoremediation of heavy metals contamination in wastewater irrigated soil systems.

The mustard (Brassica juncea L.) plant is a well-known and widely accepted hyper-accumulator of heavy metals. The genetic makeup of mustard's cultivars may significantly impact their phytoremediation capabilities. The present study aimed to investigate the growth performance, yield attributes, and heavy metal accumulation potential of B. juncea cv. Varuna, NRCHB 101, RH 749, Giriraj, and Kranti, cultivated in soil irrigated with wastewater (EPS) and bore-well water (MPS). EPS contributed more Cr, Cd, Cu, Zn, and Ni to tested mustard cultivars than the MPS. EPS reduced morphological, biochemical, physiological, and yield attributes of tested mustard cultivars significantly (p < 0.05) than the MPS. Among the tested cultivars of mustard plants, Varuna had the highest heavy metal load with the lowest harvest index (35.8 and 0.21, respectively). Whereas NRCHB 101 showed the lowest heavy metal load with the highest harvest index (26.9 and 0.43, respectively). The present study suggests that B. juncea cv. Varuna and NRCHB 101 could be used for the phytoextraction of heavy metals and reducing their contamination in food chain, respectively in wastewater irrigated areas of peri-urban India. The outcomes of the present study can also be utilized to develop a management strategy for sustainable agriculture in heavy metal polluted areas resulting from long-term wastewater irrigation.

First Case of Nocardia wallacei From India: A Case Report and Literature Review.

Nocardia is a type of bacteria that can cause infections in both immunocompromised and immunocompetent hosts. It is an obligate aerobe and is commonly found in the environment. Pulmonary nocardiosis may present as pneumonia, endobronchial inflammatory masses, lung abscess, and cavitary disease with contiguous extension, leading to effusion and empyema. We present a case of pulmonary nocardiosis in a 75-year-old male patient with type 2 diabetes mellitus. The patient presented with bilateral pneumonia and hypoxia with an oxygen saturation of 85%. Sputum samples were sent to the microbiology laboratory for testing. Acid-fast staining with 1% H2SO4 showed acid-fast branching filamentous rods, but Nocardia could not be isolated in culture. The sample was subjected to 16S rRNA gene sequencing, which identified the pathogen as Nocardia wallacei. The culture of the sputum did not grow any pathogenic organisms, and the blood culture was sterile. Unfortunately, the patient left the hospital against medical advice as he was advised for intubation. The patient could not survive and died the next day after leaving the hospital. N. wallacei can be fatal and cause disseminated infection in both immunosuppressed and immunocompetent patients. Only eight case reports of N. wallacei have been reported in the literature from various parts of the world. Our case is the first case report of N. wallacei from India.

Effect of Intraligamentary Tramadol Hydrochloride on Anesthetic Success During Endodontic Management of Mandibular Molars: A Randomized Clinical Controlled Trial.

OBJECTIVE: Tramadol hydrochloride has shown local anesthetic properties similar to lidocaine, apart from a central analgesic effect. The present study evaluated the effect of the administration of tramadol alone or in addition to 2% lidocaine, as supplementary intraligamentary injections. METHODS: One hundred and five patients, with a failed primary inferior alveolar nerve block (IANB), were randomly allocated to one of the three supplementary intraligamentary groups: 2% lidocaine with 1: 80,000 epinephrine; tramadol hydrochloride (50 mg/mL); and 2% lidocaine with 1: 80,000 epinephrine plus tramadol hydrochloride. Patients received 1.2 mL doses (0.6 mL of each root). Patients reporting pain ≤54 on Heft Parker visual analogue scale (Heft-Parker VAS), were categorized as successful anesthesia. A finger pulse oximeter was used to measure the heart rates. The anesthetic success rates, gender, and type of tooth were compared using the Pearson chi-square test. The heart rates and age were statistically evaluated using the one-way analysis of variance test. The level of significance was set at 0.05 (p=0.05). RESULTS: The initial IANB was successful in 31% of cases. There were significant differences in the anesthetic success rates of different supplementary intraligamentary injections (χ2= 33.6, p<0.001, df=2). The 2% lidocaine-plus-tramadol resulted in significantly higher success rates than the two groups. There were no significant changes in the baseline heart rates of all groups (p>0.05). CONCLUSION: The addition of tramadol to 2% lidocaine with 1: 80,000 epinephrine, given as supplementary intraligamentary injection, can help in achieving successful anesthesia during the endodontic management of mandibular molars with irreversible pulpitis resistant to IANB injections.

Insights into the management of food waste in developing countries: with special reference to India.

Up to one third of the food that is purposely grown for human sustenance is wasted and never consumed, with adverse consequences for the environment and socio-economic aspects. In India, managing food waste is a significant environmental concern. Food waste output is increasing in Indian cities and towns as a result of the country's urban expansion, modernization, and population growth. Poor management of food waste can have negative consequences for the environment and pose a risk to the public's health issues. This review focuses on the current challenges, management strategies, and future perspectives of food waste management in India. The efficient management of food waste involves a comprehensive study regarding the characterization of food waste and improved waste management methods. In addition, the government policies and rules for managing food waste that is in effect in India are covered in this review.

Immunogenicity of cancer cells: An overview.

The immune system assumes a pivotal role in the organism's capacity to discern and obliterate malignant cells. The immunogenicity of a cancer cell pertains to its proficiency in inciting an immunological response. The prowess of immunogenicity stands as a pivotal determinant in the triumph of formulating immunotherapeutic methodologies. Immunotherapeutic strategies include immune checkpoint inhibitors, chimeric antigen receptor (CAR) T-cell therapy, and on vaccines. Immunogenic cell death (ICD) epitomizes a form of cellular demise that incites an immune response against dying cells. ICD is characterized by the liberation of distinct specific molecules that activate the immune system, thereby leading to the identification and elimination of dying cells by immunocytes. One of the salient characteristics inherent to the ICD phenomenon resides in the vigorous liberation of adenosine triphosphate (ATP) by cellular entities dedicated to embarking upon the process of programmed cell death, yet refraining from complete apoptotic demise. ICD is initiated by a sequence of molecular events that occur during cell death. These occurrences encompass the unveiling or discharge of molecules such as calreticulin, high-mobility group box 1 (HMGB1), and adenosine triphosphate (ATP) from dying cells. These molecules act as "eat me" signals, which are recognized by immune cells, thereby prompting the engulfment and deterioration of expiring cells by phagocytes including various pathways such as Necroptosis, Apoptosis, and pyroptosis. Here, we review our current understanding of the pathophysiological importance of the immune responses against dying cells and the mechanisms underlying their activation. Overall, the ICD represents an important mechanism by which the immune system recognizes and eliminates dying cells, including cancer cells. Understanding the molecular events that underlie ICD bears the potential to engender innovative cancer therapeutics that harness the power of the immune system to combat cancer.

The Efficacy of Angiotensin Receptor-Neprilysin Inhibitor Versus Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Post Myocardial Infarction: A Meta-Analysis.

Acute myocardial infarction (MI) is one of the leading global healthcare emergencies, contributing to over three million global deaths. The purpose of this study is to investigate further the efficacy of sacubitril/valsartan over angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in reducing the risk of heart failure (HF) in post-MI patients and providing a clear evidence-based medicine guideline for future use. An electronic database search was conducted on English databases. Eight articles were included, fulfilling our inclusion criteria, i.e., adult patients of ≥18 years with a recent diagnosis of acute MI. Pooled analysis was done using Review Manager version 5.4.1 (Cochrane Collaboration, London, England), and the data for each outcome were analyzed as dichotomous variables. A total of eight clinical trials were included in the meta-analysis. Six studies analyzed the sacubitril/valsartan and ACEI combination. The pooled analysis reported a significant increase in the risk of hypotension (relative risk {RR}: 1.29 {1.18, 1.41}) in the sacubitril/valsartan compared to the ACEI alone group. In addition, a significant increase was observed in the left ventricle ejection fraction (LVEF) after using the sacubitril/valsartan combination compared to using ACEI alone (RR: 3.08 {2.68, 4.48}). Furthermore, no significant difference was observed between the groups in terms of mortality rate (RR: 0.86 {0.73, 1.02}), the risk of heart failure (RR: 0.62 {0.39, 1.00}), the frequency of recurrent MI (RR: 0.86 {0.27, 2.76}), and the mean difference of N-terminal pro-B-type natriuretic peptide (NT-proBNP) (weighted mean difference {WMD}: -174.36 {-414.18, 65.46}) between both the groups. However, the sacubitril/valsartan combination proved to be beneficial in significantly reducing the risk of major adverse cardiac events (MACE) (RR: 0.64 {0.48, 0.84}) and rehospitalizations (RR: 0.53 {0.39, 0.71}) as compared to ACEI post MI. Additionally, sacubitril/valsartan and ARB's combination was reported in two studies. This led to a significant decrease in NT-proBNP concentration (WMD: -71.91 {-138.43, -5.39}) post MI in the sacubitril/valsartan combination group compared to the ARB usage alone. However, no significant difference was observed in the improvement of LVEF (WMD: 0.88 {-5.11, 6.87}) between both groups. Although the sacubitril/valsartan combination has no difference in mortality and outcomes compared to ACEI, there is evidence that using it proves to be more beneficial post MI compared to ACEI and ARB usage alone.

Integrating Synthesis, Physicochemical Characterization, and In Silico Studies of Cordycepin-Loaded Bovine Serum Albumin Nanoparticles.

Cordycepin gets rapidly metabolized in the body into inactive form due to its structural similarity to adenosine, thus inhibiting its development as a medicinal agent. This study was aimed to improve the solubility and stability of cordycepin, a potential drug with known antiproliferative activity, by encapsulating it in bovine serum albumin: ß-cyclodextrin nanoparticles. Cordycepin-loaded nanoparticles (CLNPs) were synthesized using the antisolvent method and characterized thoroughly using various techniques. Our dynamic light scattering measurement showed a particle size and zeta potential of 160 ± 2.75 nm and -20.21 ± 2.1 mV, respectively, for CLNPs. Transmission electron microscopy studies revealed that particles were spherical in morphology. These CLNPs showed sustained release of cordycepin with encapsulation and loading efficiency of 81.62 ± 1.5 and 27.02 ± 2.0%, respectively, based on high-performance liquid chromatography and UV-vis studies. Based on differential scanning calorimetry and zeta potential studies, CLNPs improve cordycepin stability and solubility. Our molecular simulations and binding energy calculation also showed favorable protein interaction between cordycepin, bovine serum albumin, and ß-cyclodextrin, further supporting the notion of improved stability. In vitro cytotoxicity, apoptosis, and cellular uptake studies on breast cancer cells showed that the synthesized nanoparticles had greater cytotoxicity as compared to free cordycepin.

Frequency and Factors of Sleep Paralysis Among Medical Students of Karachi.

INTRODUCTION: Sleep paralysis is a prevalent phenomenon characterized by suffocation, immobility, and hallucinations. Its causes remain unknown, although the neurotransmitter imbalance is suggested as a potential factor. This condition is closely associated with hallucinations and a sense of intrusion, often observed in patients with narcolepsy, hypertension, and seizures. METHODS: A cross-sectional study was conducted in various medical colleges in Karachi, involving 297 participants aged 18 to 30 years. The participants were divided into groups based on gender and year of study. They were surveyed about the frequency of sleep paralysis episodes, their beliefs about the phenomenon, sleep routines, and academic impacts. RESULTS: Among the respondents, a significant number of females (n=209, 70.3%) reported experiencing sleep paralysis. The overall mean age was 20±2.0 years. Correlation analysis revealed an insignificant relationship between depression and mental anxiety (p=0.147). Similarly, no significant association was found when comparing the occurrence of sleep paralysis (p=0.16). However, a notable finding was the significant link between sleep paralysis and its impact on academics (p=0.043). CONCLUSION: This study highlighted the frequency of sleep paralysis among medical students, particularly among females. Furthermore, it emphasizes the diverse beliefs held by individuals regarding these frightening episodes. To address this neglected issue, it is essential to conduct awareness sessions aimed at understanding and alleviating sleep paralysis in individuals' lives.

Innovative Approaches and Therapies to Enhance Neuroplasticity and Promote Recovery in Patients With Neurological Disorders: A Narrative Review.

Brain rehabilitation and recovery for people with neurological disorders, such as stroke, traumatic brain injury (TBI), and neurodegenerative diseases, depend mainly on neuroplasticity, the brain's capacity to restructure and adapt. This literature review aims to look into cutting-edge methods and treatments that support neuroplasticity and recovery in these groups. A thorough search of electronic databases revealed a wide range of research and papers investigating several neuroplasticity-targeting methods, such as cognitive training, physical activity, non-invasive brain stimulation, and pharmaceutical interventions. The results indicate that these therapies can control neuroplasticity and improve motor, mental, and sensory function. In addition, cutting-edge approaches, such as virtual reality (VR) and brain-computer interfaces (BCIs), promise to increase neuroplasticity and foster rehabilitation. However, many issues and restrictions still need to be resolved, including the demand for individualized treatments and the absence of defined standards. In conclusion, this review emphasizes the significance of neuroplasticity in brain rehabilitation. It identifies novel strategies and treatments that promise to enhance recovery in patients with neurological illnesses. Future studies should concentrate on improving these therapies and developing evidence-based standards to direct clinical practice and enhance outcomes for this vulnerable population.

A novel cobalt(ii) acetate complex bearing lutidine ligand: a promising electrocatalyst for oxygen evolution reaction.

Developing cost-effective electrocatalysts using earth-abundant metal as an alternative to expensive precious metal catalyst remains a key challenge for researchers. Several strategies are being researched/tested for making low-cost transition metal complexes with controlled electron-density and coordination flexibility around the metal center to enhance their catalytic activity. Herein, we report a novel lutidine coordinated cobalt(ii) acetate complex [(3,5-lutidine)2Co(OAc)2(H2O)2] (1) as a promising electrocatalyst for oxygen evolution reaction (OER). Complex 1 was characterized by FT-IR, elemental analysis, and single crystal X-ray diffraction data. The structure optimization of complex 1 was also done using DFT calculation and the obtained geometrical parameters were found to be in good agreement with the parameters obtained from the solid state structure obtained through single crystal X-ray diffraction data. Further, the molecular electrostatic potential (MEP) maps analysis of complex 1 observed electron rich centers that were found to be in agreement with the solid-state structure. It was understood that the coordination of lutidine as a Lewis base and acetate moiety as a flexible ligand will provide more coordination flexibility around the metal center to facilitate the catalytic reaction. Further, the electron rich centers around metal center will also support the enhancement of their catalytic activity. Complex 1 shows impressive OER activity, even better than the state-of-the-art IrO2 catalyst, in terms of turnover frequency (TOF: 0.05) and onset potential (1.50 V vs. RHE). The TOF for complex 1 is two and half times higher, while the onset potential is ca. 20 mV lower, than the benchmark IrO2 catalyst studied under identical conditions.

Synthesis of polycationic nanoparticles for microbial inhibition and killing.

Antimicrobial polymers (AMP) appear to be a promising candidate to deal with the current scenario of bacterial resistance against conventional drugs and antibiotics as they mainly depend on disrupting the bacterial membrane. This work investigates the effect of polycations bearing aromatic and aliphatic pendant cationic groups on the antimicrobial performance of AMP. A radical polymerization strategy was adopted to synthesize two different copolymers and convert them into polycations upon post-modification. Polyelectrolytes were converted into nanoparticles by nanoprecipitation and named PE1 and PE2. Polymers were analyzed by NMR, FT-IR, and gel permeation chromatography (GPC). PE1 and PE2 nanoparticles were uniform, spherical particles from FESEM, size, and zeta potential measurements. The antimicrobial properties of polyelectrolytes were determined against pathogenic Escherichia coli (E. coli), Bacillus Subtilis (B. Subtilis), Bacillus Amyloliquefaciens (B. Amyloliquefaciens) and Citrobecter Freundii (C. Freundii) bacterias. The biocidal activity determination studies showed that polyelectrolyte PE2 with aromatic pendant units outperformed PE1 with the aliphatic pendant group. This work highlights the remarkable effect of aromatic segmentation, which provides microbial inhibition, and killing is demonstrated as an antibacterial surface coating.