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Abstract Background Over the last few decades, river ecosystem is highly modified through various anthropogenic activities which are resulted to alter ecosystem functions and services. This modified ecosystem rendering conducive environment to mosquitoes through various ecological links for the self-sustaining populations. However, deciphering the community assemblage of immature mosquitoes with reference to water quality at modified ecosystem is very essential to make suitable control measure to curtail mosquito populations. In order to understand how the water quality influences the larval density, habitat specificity and community assemblage of immature mosquito populations, a study was conducted at different ecosystems (urban, semi-urban and rural) along the Vaigai river. The physicochemical parameters such as pH, TDS, salinity, conductivity, turbidity, DO, were analyzed at each study site. Results Our results clearly revealed that Anopheline species were highly preferred to breed less polluted habitat than Culicine species. Community assemblage by Anopheline and Culicine mosquitoes were found to be higher at all the studies whilst community assemblage by Anopheline were maximum at rural and semi-urban sites. Among the Anopheline species, Anopheles subpictus able to breed at high polluted habitat, particularly higher turbid level (28.49 ± 2.18 NTU) than other Anopheles species. Cx. gelidus mostly breed at sewage disposal habitats with high salinity level (1.01 ± 0.08) whilst Cx. bitaeniorhynchus bred in only fresh water bodies particularly low turbid habitats (3.97 ± 0.40 NTU). Grouping of immature mosquitoes based on the habitat similarity, An. subpictus, Cx. vishnui, An. vagus, Cx. tritaeniorhynchus, Cx. gelidus and Cx. quinquefasciatus were able to breed in highly polluted habitats which are resulted fell in group A than group B mosquitoes. Cx. vishnui and An. subpictus have strong habitat similarity (0.96) and can able to share their habitats with more number of Anopheline and Culicine mosquitoes. Conclusions From the study we concluded that, Cx. vishnui and An. subpictus were most prevalent species and strong habitats similarity along the Vaigai river basin. An. subpictus and An. vagus can adapt to breed in polluted habitats and this may be adequate to extend the vectorial capacity and disease outbreak along the Vaigai river basin.

We introduce a novel dual redox mediator synthesized by covalently linking ferrocene dicarboxylic acid (FcDA) and thionine (TH) onto a pre-treated glassy carbon electrode. This unique structure significantly enhances the electro-oxidation of dopamine (DA) and the reduction of hydrogen peroxide (H2O2), offering a sensitive detection method for both analytes. The electrode exhibits exceptional sensitivity, selectivity, and stability, demonstrating potential for practical applications in biosensing. It facilitates rapid electron transfer between the analyte and the electrode surface, detecting H2O2 concentrations ranging from 1.5 to 60 µM with a limit of detection (LoD) of 0.49 µM and DA concentrations from 0.3 to 230 µM with an LoD of 0.07 µM. The electrode’s performance was validated through real-sample analyses, yielding satisfactory results.

Eight major supply chains contribute to more than 50% of the global greenhouse gas emissions (GHG). These supply chains range from raw materials to end-product manufacturing. Hence, it is critical to accurately estimate the carbon footprint of these supply chains, identify GHG hotspots, explain the factors that create the hotspots, and carry out what-if analysis to reduce the carbon footprint of supply chains. Towards this, we propose an enterprise decarbonization accelerator framework with a modular structure that automates carbon footprint estimation, identification of hotspots, explainability, and what-if analysis to recommend measures to reduce the carbon footprint of supply chains. To illustrate the working of the framework, we apply it to the cradle-to-gate extent of the palm oil supply chain of a leading palm oil producer. The framework identified that the farming stage is the hotspot in the considered supply chain. As the next level of analysis, the framework identified the hotspots in the farming stage and provided explainability on factors that created hotspots. We discuss the what-if scenarios and the recommendations generated by the framework to reduce the carbon footprint of the hotspots and the resulting impact on palm oil tree yield.

Amyotrophic lateral sclerosis (ALS) is a complex systemic disease that primarily involves motor neuron dysfunction and skeletal muscle atrophy. One commonly used mouse model to study ALS was generated by transgenic expression of a mutant form of human superoxide dismutase 1 (SOD1) gene harboring a single amino acid substitution of glycine to alanine at codon 93 (G93A*SOD1). Although mutant-SOD1 is ubiquitously expressed in G93A*SOD1 mice, a detailed analysis of the skeletal muscle expression pattern of the mutant protein and the resultant muscle pathology were never performed. Using different skeletal muscles isolated from G93A*SOD1 mice, we extensively characterized the pathological sequelae of histological, molecular, ultrastructural, and biochemical alterations. Muscle atrophy in G93A*SOD1 mice was associated with increased and differential expression of mutant-SOD1 across myofibers and increased MuRF1 protein level. In addition, high collagen deposition and myopathic changes sections accompanied the reduced muscle strength in the G93A*SOD1 mice. Furthermore, all the muscles in G93A*SOD1 mice showed altered protein levels associated with different signaling pathways, including inflammation, mitochondrial membrane transport, mitochondrial lipid uptake, and antioxidant enzymes. In addition, the mutant-SOD1 protein was found in the mitochondrial fraction in the muscles from G93A*SOD1 mice, which was accompanied by vacuolized and abnormal mitochondria, altered OXPHOS and PDH complex protein levels, and defects in mitochondrial respiration. Overall, we reported the pathological sequelae observed in the skeletal muscles of G93A*SOD1 mice resulting from the whole-body mutant-SOD1 protein expression.

Cannabis and its natural derivatives have emerged as promising therapeutics for multiple pathological and nonpathological medical conditions. For example, cannabinoids, the most popular and biologically active chemicals in cannabis, aid in many clinical ailments, including pain, inflammation, epilepsy, sleep disturbances or insomnia, multiple sclerosis, anorexia, schizophrenia, neurodegenerative diseases, anti­nausea, and most importantly, cancer. Despite the comprehensive benefits, certain aspects of cannabis present unique challenges in the medical cannabis landscape. Recent studies have highlighted the inherent challenges associated with cannabinoids' formulation like low solubility, rapid metabolism, poor bioavailability, and erratic pharmacokinetics – all of which contribute to the limited efficacy of cannabinoids. Several efforts are underway to address the bottlenecks and modify the formulations along with the delivery systems to achieve greater solubility/bioavailability, potency, and efficacy in treatment settings while minding the necessary standards for purity associated with the pharmaceutical industry. The current article presents a perspective on (1) a working knowledge of cannabinoids and their mechanisms of action, (2) the landscape of using medicinal cannabis for cancer-related medical conditions along with adversities, (3) current approaches, formulations, and challenges in medicinal cannabis delivery systems (oral, transdermal, pulmonary, and transmucosal), and lastly, (4) emerging approaches to improve delivery systems.

Abstract The antioxidant L‐Carnosine is reported to improve negative and cognitive symptoms in Schizophrenia. A randomized double‐blind placebo‐controlled study was planned to study the effectiveness of adjuvant L‐Carnosine therapy in patients with Schizophrenia. 100 eligible patients with predominant negative symptoms as measured by scale for assessment of negative symptoms (SANS total score ≥ 60) and Schizophrenia diagnosis (International Classification of Disorder‐Tenth Edition, ICD‐10) were recruited. They were randomly allocated to receive a fixed dose of either 400 mg L‐Carnosine or identical placebo for 3 months and increased to 800 mg from 13th week till completion of study. Primary outcome measures assessed changes in SANS scores with L‐Carnosine at 24 weeks compared to baseline, 4 and 12 weeks. Secondary outcome measures were done to assess the improvement in cognitive symptoms (executive function, attention, and memory) at 24 weeks using subtests of NIMHANS (National Institute for Mental Health and Neurosciences) cognitive battery. Side effects were assessed using adverse events reporting form. The attention scores (p = .023) showed significant differences in patients receiving 800 mg of L‐Carnosine at the end of the study. There were no significant differences in negative symptoms in the two arms at study completion. L‐Carnosine dosing of 800 mg may be a promising agent to enhance executive functions in Schizophrenia.

Ischemic stroke is one of the leading causes of death and disability worldwide. Neurogenesis plays a crucial role in postischemic functional recovery. Alcohol dose-dependently affects the prognosis of ischemic stroke. We investigated the impact of light alcohol consumption (LAC) on neurogenesis under physiological conditions and following ischemic stroke. C57BL/6J mice (three months old) were fed with 0.7 g/kg/day ethanol (designed as LAC) or volume-matched water (designed as control) daily for eight weeks. To evaluate neurogenesis, the numbers of 5-bromo-2-deoxyuridine (BrdU)+/doublecortin (DCX)+ and BrdU+/NeuN+ neurons were assessed in the subventricular zone (SVZ), dentate gyrus (DG), ischemic cortex, and ischemic striatum. The locomotor activity was determined by the accelerating rotarod and open field tests. LAC significantly increased BrdU+/DCX+ and BrdU+/NeuN+ cells in the SVZ under physiological conditions. Ischemic stroke dramatically increased BrdU+/DCX+ and BrdU+/NeuN+ cells in the DG, SVZ, ischemic cortex, and ischemic striatum. The increase in BrdU+/DCX+ cells was significantly greater in LAC mice compared to the control mice. In addition, LAC significantly increased BrdU+/NeuN+ cells by about three folds in the DG, SVZ, and ischemic cortex. Furthermore, LAC reduced ischemic brain damage and improved locomotor activity. Therefore, LAC may protect the brain against ischemic stroke by promoting neurogenesis.

Autotaxin (ATX) is an extracellular secretory enzyme (lysophospholipase D) that catalyzes the hydrolysis of lysophosphatidyl choline to lysophosphatidic acid (LPA). The ATX–LPA axis is a well-known pathological mediator of liver fibrosis, metastasis in cancer, pulmonary fibrosis, atherosclerosis, and neurodegenerative diseases. Additionally, it is believed that LPA may cause vascular permeability. In ischemic stroke, vascular permeability leading to hemorrhagic transformation is a major limitation for therapies and an obstacle to stroke management. Therefore, in this study, we generated an endothelial-specific ATX deletion in mice (ERT2 ATX−/−) to observe stroke outcomes in a mouse stroke model to analyze the role of endothelial ATX. The AR2 probe and Evans Blue staining were used to perform the ATX activity and vascular permeability assays, respectively. Laser speckle imaging was used to observe the cerebral blood flow following stroke. In this study, we observed that stroke outcomes were alleviated with the endothelial deletion of ATX. Permeability and infarct volume were reduced in ERT2 ATX−/− mice compared to ischemia–reperfusion (I/R)-only mice. In addition, the cerebral blood flow was retained in ERT2 ATX−/− compared to I/R mice. The outcomes in the stroke model are alleviated due to the limited LPA concentration, reduced ATX concentration, and ATX activity in ERT2 ATX−/− mice. This study suggests that endothelial-specific ATX leads to increased LPA in the brain vasculature following ischemic–reperfusion and ultimately disrupts vascular permeability, resulting in adverse stroke outcomes.

The main objective of the present study is to highlight the most favourable set of 1D selective experiments based on NMR relaxation and NOE to elucidate inclusion geometry of cyclodextrin based host-guest complexes. Prediction of the mode of insertion of a model drug diflunisal (DFL) inside β-Cyclodextrin (β-CD) and 2-hydroxylpropyl-β-Cyclodextrin (HP- β-CD) has been attempted by employing one dimensional (1D) selective NMR experiments. The respective spectral complexity observed in case of β-CD and HP-β-CD inclusion complexes dictates the choice of selective measurements. A combination of non-selective (R1ns), selective (R1se) and bi-selective (R1bs) spin-lattice relaxation rate measurements has exhibited potential in quantifying molecular rotational correlation time (τc) and prediction of mode of insertion for DFL:β-CD complex while in case of DFL:HP-β-CD complex selective ROE experiment is the valid alternative to extract the inter nuclear distance data. In both the cases the fluorinated ring of DFL remains outside the CD cavity. Further, the observation of higher shift of chemical shift positions, enhanced peak intensities, slightly shorter spin-lattice relaxation times and slower molecular motion in case of HP-β-CD complex compared to the β-CD complex clearly suggested a better encapsulation of the drug by the former. In conclusion, 1D selective ROESY will be a superior method for intermediate sized CD inclusion complexes while multi-selective relaxation experiments are apt for non-intermediate sized inclusion complexes with better peak resolution.

Helicobacter pylori (H. pylori) is a common gastric pathogen that infects approximately half of the world's population. Infection with H. pylori can lead to diverse pathological conditions, including chronic gastritis, peptic ulcer disease, and cancer. The latter is the most severe consequence of H. pylori infection. According to epidemiological studies, gastric infection with H. pylori is the strongest known risk factor for non-cardia gastric cancer (GC), which remains one of the leading causes of cancer-related deaths worldwide. However, it still remains to be poorly understood how host-microbe interactions result in cancer development in the human stomach. Here we focus on the H. pylori bacterial factors that affect the host ubiquitin proteasome system. We investigated E3 ubiquitin ligases SIVA1 and ULF that regulate p14ARF (p19ARF in mice) tumor suppressor. ARF plays a key role in regulation of the oncogenic stress response and is frequently inhibited during GC progression. Expression of ARF, SIVA1 and ULF proteins were investigated in gastroids, H. pylori-infected mice and human gastric tissues. The role of the H. pylori type IV secretion system was assessed using various H. pylori isogenic mutants. Our studies demonstrated that H. pylori infection results in induction of ULF, decrease in SIVA1 protein levels, and subsequent ubiquitination and degradation of p14ARF tumor suppressor. Bacterial CagA protein was found to sequentially bind to SIVA1 and ULF proteins. This process is regulated by CagA protein phosphorylation at the EPIYA motifs. Downregulation of ARF protein leads to inhibition of cellular apoptosis and oncogenic stress response that may promote gastric carcinogenesis.

Lysophosphatidic acid (LPA), a multifunctional endogenous phospholipid, plays a vital role in cellular homeostasis and the malignant behavior of cancer cells through G-protein-coupled receptors. However, the role of LPA in β-catenin-mediated gastric cancer is unknown. Here, we have noted the high expression of LPAR2 in human gastric cancer tissues, and that LPA treatment significantly increased the proliferation, migration, and invasion of human gastric cancer cells. Results from our biochemical experiments showed that an LPA exposure increased the expression of β-catenin and its nuclear localization, increased the phosphorylation of glycogen synthase kinase 3β (GSK-3β), decreased the expression of Axin2, and increased the expression of the target genes of the β-catenin signaling pathway. The LPA2 receptor (LPAR2) antagonist significantly reduced the LPA-induced nuclear localization of β-catenin, the primary signaling event. The knockdown of LPAR2 in the gastric cancer cell lines robustly reduced the LPA-induced β-catenin activity. An LPA exposure increased the ATP production by both oxidative phosphorylation and glycolysis, and this effect was abrogated with the addition of an LPAR2 antagonist and XAV393, which stabilizes the Axin and inhibits the β-catenin signaling pathway. Based on our findings, the possibility that LPA contributes to gastric cancer initiation and progression through the β-catenin signaling pathway as well as by the dysregulation of the energy metabolism via the LPAR2 receptor and Axin2, respectively, provides a novel insight into the mechanism of and possible therapeutic targets of gastric cancer.

Different shaped floating wick (FW) material in the basin improved the efficacy of a single slope solar still (SS). Thermocol is used to support a basin in which cotton wicks are suspended. The three forms of modified solar stills (MSS) are analyzed, each with a unique absorber geometry. Absorber surfaces in the MSS-RCT (Rectangular teeth), MSS-ITT (Isosceles Triangular teeth), and MSS-HCT (Half-circular teeth) configurations are made up of FW layers. These improved designs are far more efficient and effective than the Conventional solar still (CSS). All MSS absorber surfaces produce more potable water than the CSS experiment does for the bulk of the workday. The MSS-HCT process achieved a maximum daily yield that was on par with that of the other modified stills and a 68 % increase in daily yield compared to the CSS process.

Chronic alcohol consumption dose-dependently affects the incidence and prognosis of ischemic stroke. We determined the influence of chronic alcohol consumption on cerebral angiogenesis under physiological conditions and following ischemic stroke. In in vitro studies, acute exposure to low-concentration ethanol significantly increased angiogenic capability and upregulated vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor receptor 2 (VEGFR2) in C57BL/6J mouse brain microvascular endothelial cells (MBMVECs). The increased angiogenic capability was abolished in the presence of a VEGFR2 inhibitor. In addition, the increased angiogenic capability and upregulated VEGF-A and VEGFR2 remained in chronically low-concentration ethanol-exposed MBMVECs. In in vivo studies, 8-week gavage feeding with low-dose ethanol significantly increased vessel density and vessel branches and upregulated VEGF-A and VEGFR2 in the cerebral cortex under physiological conditions. Furthermore, vessel density, vessel branches, and expression of VEGF-A and VEGFR2 in the peri-infarct cortex were significantly greater in low-dose ethanol-fed mice at 72 h of reperfusion. Although low-dose ethanol did not alter cerebral vasoreactivity and regional cerebral blood flow (rCBF) either before or during ischemia, it significantly augmented post-ischemic hyperemia during reperfusion. In contrast, exposure to high-concentration ethanol and 8-week gavage feeding with high-dose ethanol only had a mild inhibitory effect on angiogenic capability and cerebral angiogenesis, respectively. We conclude that heavy alcohol consumption may not dramatically alter cerebral angiogenesis, whereas light alcohol consumption significantly promotes cerebral angiogenesis.

Reactive oxygen species (ROS), a by-product of aerobic life, are highly reactive molecules with unpaired electrons. The excess of ROS leads to oxidative stress, instigating the peroxidation of polyunsaturated fatty acids (PUFA) in the lipid membrane through a free radical chain reaction and the formation of the most bioactive aldehyde, known as 4-hydroxynonenal (4-HNE). 4-HNE functions as a signaling molecule and toxic product and acts mainly by forming covalent adducts with nucleophilic functional groups in proteins, nucleic acids, and lipids. The mitochondria have been implicated as a site for 4-HNE generation and adduction. Several studies clarified how 4-HNE affects the mitochondria’s functions, including bioenergetics, calcium homeostasis, and mitochondrial dynamics. Our research group has shown that 4-HNE activates mitochondria apoptosis-inducing factor (AIFM2) translocation and facilitates apoptosis in mice and human heart tissue during anti-cancer treatment. Recently, we demonstrated that a deficiency of SOD2 in the conditional-specific cardiac knockout mouse increases ROS, and subsequent production of 4-HNE inside mitochondria leads to the adduction of several mitochondrial respiratory chain complex proteins. Moreover, we highlighted the physiological functions of HNE and discussed their relevance in human pathophysiology and current discoveries concerning 4-HNE effects on mitochondria.

Background The loss of endothelial integrity increases the risk of intracerebral hemorrhage during ischemic stroke. Adjunct therapeutic targets for reperfusion in ischemic stroke are in need to prevent blood‐brain barrier disruption. Recently, we have shown that endothelial permeability is mediated by lysophosphatidic acid (LPA), but the role of autotaxin, which produces LPA, remains unclear in stroke. We investigate whether autotaxin/LPA axis regulates blood‐brain barrier integrity after cerebral ischemia. Methods and Results Ischemic stroke was induced in mice by middle cerebral artery occlusion for 90 minutes, followed by 24‐hour reperfusion. The therapeutic efficacy of autotaxin/LPA receptor blockade was evaluated using triphenyl tetrazolium chloride staining, Evans blue permeability, infrared imaging, mass spectrometry, and XF24 analyzer to evaluate blood‐brain barrier integrity, autotaxin activity, and mitochondrial bioenergetics. In our mouse model of ischemic stroke, the mRNA levels of autotaxin were elevated 1.7‐fold following the cerebral ischemia and reperfusion (I/R) group compared with the sham. The enzymatic activity of autotaxin was augmented by 4‐fold in the I/R group compared with the sham. Plasma and brain tissues in I/R group showed elevated LPA levels. The I/R group also demonstrated mitochondrial dysfunction, as evidenced by decreased (P

The development of treatment processes from laboratory scale to industries involves a lot of troubles due to the automation of process parameters and fluctuated characteristics of wastewater. In the present study, six different real-time textile effluents of samples such as S1 to S6 are characterized and treated by electrocoagulation process using Stainless Steel (SS) and Aluminum (Al) electrodes. The maximum removal efficiencies of color as 94%, turbidity as 99%, Chemical Oxygen Demand (COD) as 84% and Biological Oxygen Demand (BOD) as 82% is obtained for effluent sample S1 with fixed operational conditions such as the applied voltage of 4V, inter-electrode distance of 3 cm, the surface area of the electrode of 25 cm2 and agitation speed of 500 rpm respectively. After the electrocoagulation process, the BOD5/COD ratio of all effluent samples is observed as biodegradable limits. Under the fixed conditions, the operational cost for the treatment of effluent sample S1 analyzed as 2.42 and 1.01 $/m3 by using SS and Al electrodes respectively.

This paper deals with a study conducted on flexural behavior of cold-formed steel built-up I-beams with hollow tubular flange sections. There were two types of test sections, namely, built-up sections that were assembled with either stiffened or unstiffened channels coupling back-to-back at the web and a hollow tubular rectangular flange at the top and bottom of the web to form built-up I-beam. The flexural behavior along with the strength and failure modes of the built-up sections was examined using the four-point loading system. Nonlinear finite element (FE) models were formulated and validated with the experimental test results. It was observed that the developed FE models had precisely predicted the behavior of built-up I-beams. Further, the verified FE models were used to conduct a detailed parametric study on cold-formed steel built-up beam sections with respect to thickness, depth, and yield stress of the material. The flexural strength of the beams was designed using the direct strength method as specified in American Iron and Steel Institute (AISI) for the design of cold-formed steel structural members and was compared with the experimental results and the failure loads predicted from FE models. Since the results were not conservative, a new customized design equation had been mooted and delineated in the study for determining the flexural strength of cold-formed steel built-up beams with hollow tubular flange sections.