An immunoinformatic approach for developing a multi-epitope subunit vaccine against Monkeypox virus.

An in-silico approach was implemented to develop a multi-epitope subunit vaccine construct against the recent outbreak of the Monkeypox virus. The contribution of 10 different antigenic proteins based on their antigenicity led to the selection of 10 HTL, 9 CTL, and 6 BCL epitopes. The construct was further investigated for its allergenicity, antigenicity, and physio-chemical properties using servers such as AllerTOP and Allergen FP, VaxiJen and ANTIGENPro, and ProtParam respectively. The secondary structure of the vaccine was predicted using the SOPMA server followed by I-TASSER for the 3D structure. After refinement and validation of structural stability of the modelled vaccine, a molecular docking assay was implemented to study the interaction of the known TLR4 receptor with that of the constructed vaccine using the ClusPro server. The docked vaccine and TLR4 receptor were studied using the molecular dynamics (MD) simulation to validate the stability of the complex. After codon optimization the cDNA was constructed and in-silico cloning of the vaccine construct was carried out. The vaccine was also subjected to computational immune assay which predicted a powerful immune response against the Monkeypox virus validating that the developed multi-epitope vaccine construct can be a potent vaccine candidate. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-024-00220-5.

Contamination of textile dyes in aquatic environment: Adverse impacts on aquatic ecosystem and human health, and its management using bioremediation.

Textile dyes are the burgeoning environmental contaminants across the world. They might be directly disposed of from textile industries into the aquatic bodies, which act as the direct source for the entire ecosystem, ultimately impacting the human beings. Hence, it is essential to dissect the potential adverse outcomes of textile dye exposure on aquatic plants, aquatic fauna, terrestrial entities, and humans. Analysis of appropriate literature has revealed that textile dye effluents could affect the aquatic biota by disrupting their growth and reproduction. Various aquatic organisms are targeted by textile dye effluents. In such organisms, these chemicals affect their development, behavior, and induce oxidative stress. General populations of humans are exposed to textile dyes via the food chain and drinking contaminated water. In humans, textile dyes are biotransformed into electrophilic intermediates and aromatic amines by the enzymes of the cytochrome family. Textile dyes and their biotransformed products form the DNA and protein adducts at sub-cellular moiety. Moreover, these compounds catalyze the production of free radicals and oxidative stress, and trigger the apoptotic cascades to produce lesions in multiple organs. In addition, textile dyes modulate epigenetic factors like DNA methyltransferase and histone deacetylase to promote carcinogenesis. Several bioremediation approaches involving algae, fungi, bacteria, biomembrane filtration techniques, etc., have been tested and some other hybrid systems are currently under investigation to treat textile dye effluents. However, many such approaches are at the trial stage and require further research to develop more efficient, cost-effective, and easy-to-handle techniques.

Synaptobrevin2 monomers and dimers differentially engage to regulate the functional trans-SNARE assembly.

The precise cell-to-cell communication relies on SNARE-catalyzed membrane fusion. Among ∼70 copies of synaptobrevin2 (syb2) in synaptic vesicles, only ∼3 copies are sufficient to facilitate the fusion process at the presynaptic terminal. It is unclear what dictates the number of SNARE complexes that constitute the fusion pore assembly. The structure-function relation of these dynamic pores is also unknown. Here, we demonstrate that syb2 monomers and dimers differentially engage in regulating the trans-SNARE assembly during membrane fusion. The differential recruitment of two syb2 structures at the membrane fusion site has consequences in regulating individual nascent fusion pore properties. We have identified a few syb2 transmembrane domain residues that control monomer/dimer conversion. Overall, our study indicates that syb2 monomers and dimers are differentially recruited at the release sites for regulating membrane fusion events.

Breaking boundaries: Artificial intelligence for pesticide detection and eco-friendly degradation.

Pesticides are extensively used agrochemicals across the world to control pest populations. However, irrational application of pesticides leads to contamination of various components of the environment, like air, soil, water, and vegetation, all of which build up significant levels of pesticide residues. Further, these environmental contaminants fuel objectionable human toxicity and impose a greater risk to the ecosystem. Therefore, search of methodologies having potential to detect and degrade pesticides in different environmental media is currently receiving profound global attention. Beyond the conventional approaches, Artificial Intelligence (AI) coupled with machine learning and artificial neural networks are rapidly growing branches of science that enable quick data analysis and precise detection of pesticides in various environmental components. Interestingly, nanoparticle (NP)-mediated detection and degradation of pesticides could be linked to AI algorithms to achieve superior performance. NP-based sensors stand out for their operational simplicity as well as their high sensitivity and low detection limits when compared to conventional, time-consuming spectrophotometric assays. NPs coated with fluorophores or conjugated with antibody or enzyme-anchored sensors can be used through Surface-Enhanced Raman Spectrometry, fluorescence, or chemiluminescence methodologies for selective and more precise detection of pesticides. Moreover, NPs assist in the photocatalytic breakdown of various organic and inorganic pesticides. Here, AI models are ideal means to identify, classify, characterize, and even predict the data of pesticides obtained through NP sensors. The present study aims to discuss the environmental contamination and negative impacts of pesticides on the ecosystem. The article also elaborates the AI and NP-assisted approaches for detecting and degrading a wide range of pesticide residues in various environmental and agrecultural sources including fruits and vegetables. Finally, the prevailing limitations and future goals of AI-NP-assisted techniques have also been dissected.

Is There Variation in Time to and Type of Treatment for Hip Osteoarthritis Based on Insurance?

BACKGROUND: Disparities in care access based on insurance exist for total hip arthroplasty (THA), but it is unclear if these lead to longer times to surgery. We evaluated whether rates of THA versus nonoperative interventions (NOI) and time to THA from initial hip osteoarthritis (OA) diagnosis vary by insurance type. METHODS: Using a national claims database, patients who had hip OA undergoing THA or NOI from 2011 to 2019 were identified and divided by insurance type: Medicaid-managed care; Medicare Advantage; and commercial insurance. The primary outcome was THA incidence within 3 years after hip OA diagnosis. Multivariable logistic regression models were created to assess the association between THA and insurance type, adjusting for age, sex, region, and comorbidities. RESULTS: Medicaid patients had lower rates of THA within 3 years of initial diagnosis (7.4 versus 10.9 or 12.0%, respectively; P < .0001) and longer times to surgery (297 versus 215 or 261 days, respectively; P < .0001) compared to Medicare Advantage and commercially-insured patients. In multivariable analyses, Medicaid patients were also less likely to receive THA (odds ratio (OR) = 0.62 [95% confidence intervals (CI): 0.60 to 0.64] versus Medicare Advantage, OR = 0.63 [95% CI: 0.61 to 0.64] versus commercial) or NOI (OR = 0.92 [95% CI: 0.91 to 0.94] versus Medicare Advantage, OR = 0.81 [95% CI: 0.79 to 0.82] versus commercial). CONCLUSIONS: Medicaid patients experienced lower rates of and longer times to THA than Medicare Advantage or commercially-insured patients. Further investigation into causes of these disparities, such as costs or access barriers, is necessary to ensure equitable care.

Design, manufacturing, and testing of 0.35/25 kV, 20 kHz transformers for particle accelerators.

A high voltage, high frequency transformer unit has been designed and built for powering the Cockcroft-Walton voltage multiplier to be used as part of a particle accelerator power supply at the Institute For Plasma Research, India, for the nuclear fusion research facility. A novel combination of high voltage (25 kV), high frequency (20 kHz), and high power (70 kV A) specifications makes its design distinctive and more challenging. The complete unit is composed of two 0.350/25 kV amorphous core transformers connected in center-tap configuration and immersed in an oil-filled tank. To facilitate an iterative design procedure, a spreadsheet method was utilized. The design involved a methodical approach for the core and winding selection, followed by the magnetic analysis and high voltage insulation layout through the finite element method. All the magnetic, electrical, and thermal parameters have been evaluated in detail, assuring a continuous stable operation having an efficiency of greater than 95%. Finally, the transformers were made, and preliminary experiments, including turns ratio, short-circuit, and dielectric tests, were carried out to verify the accuracy of the proposed design. The unit was also field tested under actual load conditions, and the test results were presented and corroborated with the design calculations.

Vascular miR-181b controls tissue factor-dependent thrombogenicity and inflammation in type 2 diabetes.

BACKGROUND: Diabetes mellitus is characterized by chronic vascular inflammation leading to pathological expression of the thrombogenic full length (fl) tissue factor (TF) and its isoform alternatively-spliced (as) TF. Blood-borne TF promotes factor (F) Xa generation resulting in a pro-thrombotic state and cardiovascular complications. MicroRNA (miR)s impact gene expression on the post-transcriptional level and contribute to vascular homeostasis. Their distinct role in the control of the diabetes-related procoagulant state remains poorly understood. METHODS: In a cohort of patients with poorly controlled type 2 diabetes (n = 46) plasma levels of miR-181b were correlated with TF pathway activity and markers for vascular inflammation. In vitro, human microvascular endothelial cells (HMEC)-1 and human monocytes (THP-1) were transfected with miR-181b or anti-miR-181b and exposed to tumor necrosis factor (TNF) α or lipopolysaccharides (LPS). Expression of TF isoforms, vascular adhesion molecule (VCAM) 1 and nuclear factor (NF) κB nuclear translocation was assessed. Moreover, aortas, spleen, plasma, and bone marrow-derived macrophage (BMDM)s of mice carrying a deletion of the first miR-181b locus were analyzed with respect to TF expression and activity. RESULTS: In patients with type 2 diabetes, plasma miR-181b negatively correlated with the procoagulant state as evidenced by TF protein, TF activity, D-dimer levels as well as markers for vascular inflammation. In HMEC-1, miR-181b abrogated TNFα-induced expression of flTF, asTF, and VCAM1. These results were validated using the anti-miR-181b. Mechanistically, we confirmed a miR-181b-mediated inhibition of importin-α3 (KPNA4) leading to reduced nuclear translocation of the TF transcription factor NFκB. In THP-1, miR-181b reduced both TF isoforms and FXa generation in response to LPS due to targeting phosphatase and tensin homolog (PTEN), a principal inducer for TF in monocytes. Moreover, in miR-181-/- animals, we found that reduced levels of miR-181b were accompanied by increased TF, VCAM1, and KPNA4 expression in aortic tissue as well as increased TF and PTEN expression in spleen. Finally, BMDMs of miR-181-/- mice showed increased TF expression and FXa generation upon stimulation with LPS. CONCLUSIONS: miR-181b epigenetically controls the procoagulant state in diabetes. Reduced miR-181b levels contribute to increased thrombogenicity and may help to identify individuals at particular risk for thrombosis.

Olanzapine-induced Neuroleptic Malignant Syndrome.

Neuroleptic malignant syndrome (NMS) is a life-threatening adverse effect usually seen with typical antipsychotic drugs. Rarely, NMS can occur with atypical antipsychotics also. A 19-year-old male diagnosed as a case of acute and transient psychotic disorder developed NMS, following the treatment with an atypical antipsychotic, olanzapine 20 mg/day. The patient was diagnosed NMS, an offending agent olanzapine was immediately withdrawn, and prompt treatment by maintaining hydration and giving bromocriptine produced recovery.