A Novel Cryptic Virus Isolated from Galphimia spp. in Mexico.

Galphimia spp. is a plant employed in traditional medicine in Mexico because of its anxiolytic and sedative effects. Viruses have been associated with different alterations in plants, although asymptomatic agents (i.e., cryptic viruses) are also known. High-throughput sequencing (HTS) allows for the detection of pathogenic and non-pathogenic viral agents in plants, including potential novel viruses. The aim of this study was to investigate the presence of viral agents in two populations of Galphimia spp. by HTS. Sequencing was conducted on an Illumina NextSeq 550 platform, and a putative novel virus was identified. Two contigs showed homology to partitiviruses, and these encoded the RNA-dependent RNA polymerase and coat protein. These proteins showed the highest identities with orthologs in the recently discovered Vitis cryptic virus. A phylogenetic analysis of both RNAs showed that the new virus clusters into the monophyletic genus Deltapartitivirus along with other plant-infecting viruses. The result of the HTS analysis was validated by conventional RT-PCR and Sanger sequencing. A novel virus was discovered in a symptomless Galphimia spp. plant and tentatively named the Galphimia cryptic virus (GCV). This is the first virus discovered in medicinal plants in Mexico.

PGPR-Enabled bioremediation of pesticide and heavy metal-contaminated soil: A review of recent advances and emerging challenges.

The excessive usage of agrochemicals, including pesticides, along with various reckless human actions, has ensued discriminating prevalence of pesticides and heavy metals (HMs) in crop plants and the environment. The enhanced exposure to these chemicals is a menace to living organisms. The pesticides may get bioaccumulated in the food chain, thereby leading to several deteriorative changes in the ecosystem health and a rise in the cases of some serious human ailments including cancer. Further, both HMs and pesticides cause some major metabolic disturbances in plants, which include oxidative burst, osmotic alterations and reduced levels of photosynthesis, leading to a decline in plant productivity. Moreover, the synergistic interaction between pesticides and HMs has a more serious impact on human and ecosystem health. Various attempts have been made to explore eco-friendly and environmentally sustainable methods of improving plant health under HMs and/or pesticide stress. Among these methods, the employment of PGPR can be a suitable and effective strategy for managing these contaminants and providing a long-term remedy. Although, the application of PGPR alone can alleviate HM-induced phytotoxicities; however, several recent reports advocate using PGPR with other micro- and macro-organisms, biochar, chelating agents, organic acids, plant growth regulators, etc., to further improve their stress ameliorative potential. Further, some PGPR are also capable of assisting in the degradation of pesticides or their sequestration, reducing their harmful effects on plants and the environment. This present review attempts to present the current status of our understanding of PGPR's potential in the remediation of pesticides and HMs-contaminated soil for the researchers working in the area.

Electrochemical and Plasmonic Detection of Myocardial Infarction Using Microfluidic Biochip Incorporated with Mesoporous Nanoscaffolds.

This paper reports a microfluidic device for the electrochemical and plasmonic detection of cardiac myoglobin (cMb) and cardiac troponin I (cTnI) with noticeable limits of detection (LoD) as low as a few picograms per milliliter (pg/mL) ranges, achieved in a short detection time. The device features two working electrodes, each with a mesoporous Ni3V2O8 nanoscaffold grafted with reduced graphene oxide (rGO) that improves the interaction of diffusing analyte molecules with the sensing surface by providing a high surface area and reaction kinetics. Electrochemical studies reveal sensitivities as high as 9.68 µA ng/mL and a LoD of 2.0 pg/mL for cTnI, and 8.98 µA ng/mL and 4.7 pg/mL for cMb. Additionally, the surface plasmon resonance (SPR) studies demonstrate a low-level LoD of 8.8 pg/mL for cMb and 7.3 pg/mL for cTnI. The dual-modality sensor enables dynamic tracking of kinetic antigen-antibody interactions during sensing, self-verification through providing signals of two modes, and reduced false readout. This study demonstrates the complementary nature of the electrochemical and SPR modes in biosensing, with the electrochemical mode being highly sensitive and the SPR mode providing superior tracking of molecular recognition behaviors. The presented sensor represents a significant innovation in cardiovascular disease management and can be applied to monitor other clinically important biomolecules.

Identification of a novel GSK3ß inhibitor involved in abrogating KRas dependent pancreatic tumors in Wnt/beta-catenin and NF-kB dependent manner.

Pancreatic cancer is an aggressive malignancy with a poor survival rate because it is difficult to diagnose the disease during its early stages. The currently available treatments, which include surgery, chemotherapy and radiation therapy, offer only limited survival benefit. Pharmacological interventions to inhibit Glycogen Synthase Kinase-3beta (GSK3ß) activity is an important therapeutic strategy for the treatment of pancreatic cancer because GSK3ß is one of the key factors involved in the onset, progression as well as in the acquisition of chemoresistance in pancreatic cancer. Here, we report the identification of MJ34 as a potent GSK3ß inhibitor that significantly reduced growth and survival of human mutant KRas dependent pancreatic tumors. MJ34 mediated GSK3ß inhibition was seen to induce apoptosis in a ß-catenin dependent manner and downregulate NF-kB activity in MiaPaCa-2 cells thereby impeding cell survival and anti-apoptotic processes in these cells as well as in the xenograft model of pancreatic cancer. In vivo acute toxicity and in vitro cardiotoxicity studies indicate that MJ34 is well tolerated without any adverse effects. Taken together, we report the discovery of MJ34 as a potential drug candidate for the therapeutic treatment of mutant KRas-dependent human cancers through pharmacological inhibition of GSK3ß.

Taguchi Optimization of Wetting, Thermal and Mechanical Properties of Sn-1.0wt.%Ag-0.5wt.%Cu Alloys Modified with Bi and Sb.

This study was conducted on SAC105 (Sn-1wt.%Ag-0.5wt.%Cu) lead-free solder modified with Bi and Sb. The wetting, melting point, and mechanical properties were analysed with the addition of 1~5 wt.%Bi and 1~5 wt.%Sb for SAC105 base alloy. The wetting characteristics were assessed by wetting time (zero cross time, ZCT) obtained from wetting balance tests. The mechanical properties were analysed by tensile tests. Considering two factors (Bi, Sb), a three-level (0, 1, 2 wt.%) design of experiment (DOE) method array was applied for Taguchi optimization. The results indicated that the solder wetting increased as Bi content increased, while it decreased with Sb. The ZCT decreased with increasing Bi content up to 4 wt.%, while it increased proportionally to Sb content. The melting point, measured using a differential scanning calorimeter (DSC), showed that the melting point tended to decrease according to Bi increase, while it increases depending on the Sb content. Increase in Bi and Sb levels resulted in enhanced tensile strength in the mechanical properties tests, with Bi having a more noticeable impact. The Taguchi optimized conditions for the Bi and Sb studies were found to be 2 wt.%Bi and 2 wt.%Sb. This led to an optimal set of 0.9 s of wetting time, a 222.55 °C melting point, a 55 MPa tensile strength, and a 50% elongation.

The prospect of supercapacitors in integrated energy harvesting and storage systems.

Renewable energy sources, such as wind, tide, solar cells, etc, are the primary research areas that deliver enormous amounts of energy for our daily usage and minimize the dependency upon fossil fuel. Paralley, harnessing ambient energy from our surroundings must be prioritized for small powered systems. Nanogenerators, which use waste energy to generate electricity, are based on such concepts. We refer to these nanogenerators as energy harvesters. The purpose of energy harvesters is not to outcompete traditional renewable energy sources. It aims to reduce reliance on primary energy sources and enhance decentralized energy production. Energy storage is another area that needs to be explored for quickly storing the generated energy. Supercapacitor is a familiar device with a unique quick charging and discharging feature. Encouraging advancements in energy storage and harvesting technologies directly supports the efficient and comprehensive use of sustainable energy. Yet, self-optimization from independent energy harvesting and storage devices is challenging to overcome. It includes instability, insufficient energy output, and reliance on an external power source, preventing their direct application and future development. Coincidentally, integrating energy harvesters and storage devices can address these challenges, which demand their inherent action. This review intends to offer a complete overview of supercapacitor-based integrated energy harvester and storage systems and identify opportunities and directions for future research in this subject.

Low ppm NO2 detection through advanced ultrasensitive copper oxide gas sensor.

The imperative development of a cutting-edge environmental gas sensor is essential to proficiently monitor and detect hazardous gases, ensuring comprehensive safety and awareness. Nanostructures developed from metal oxides are emerging as promising candidates for achieving superior performance in gas sensors. NO2 is one of the toxic gases that affects people as well as the environment so its detection is crucial. The present study investigates the gas sensing capability of copper oxide-based sensor for 5 ppm of NO2 gas at 100 °C. The sensing material was synthesized using a facile precipitation method and characterized by XRD, FE-SEM, UV-visible spectroscopy, photoluminescence spectroscopy, XPS and BET techniques. The developed material shows a response equal to 67.1% at optimal temperature towards 5 ppm NO2 gas. The sensor demonstrated an impressive detection limit of 300 ppb, along with a commendable percentage response of 5.2%. Under optimized conditions, the synthesized material demonstrated its high selectivity, as evidenced by the highest percentage response recorded for NO2 gas among NO2, NH3, CO, CO2 and H2S.

Modulating temperature for Cu2ZnSnS4 (CZTS) synthesis via hot injection method and studying the photocatalytic efficiencies for the degradation of Rhodamine 6G and Methylene blue pollutants.

Cu2ZnSnS4 (CZTS) was synthesized following hot injection method and the process was optimized by varying temperature conditions. Four samples at different temperatures viz., 200, 250, 300 and 350°C were prepared and analyzed using different characterization techniques. Based on the correlation between XRD, Raman and XPS, we conclude that the formation of ZnS and SnS2 occurs at 3500C but at 2000C there is no breakdown of the complex as per XRD. According to Raman and XPS analysis, as the temperature rises, the bonds between the metals become weaker, which is visibly seen in Raman and XPS due to the minor peaks of copper sulfide. Scanning electron microscopic analysis confirmed nanometric particles which increase in size with temperature. The photocatalytic evaluation showed that CZTS synthesized at 2000C performed efficiently in the removal of the two colorants, methylene blue and Rhodamine 6G, achieving 92.80% and 90.65%, respectively. The photocatalytic degradation efficiencies decreased at higher temperatures due to bigger sized CZTS particles as confirmed by SEM results. Computational simulations confirm that CZTS has a highly negative energy -25,764 Ry, confirming its structural stability and higher covalent than ionic character.

Mesoporous SO42- / kit-6-catalyzed hydrocracking of waste chicken oil.

In this study, we studied the hydrocracking of waste chicken oil (WCO) catalyzed by mesoporous SO42-/KIT-6. The study included WCO extraction, SO42-/KIT-6 catalyst synthesis, hydrocracking, and catalytic characterization. XRD patterns revealed intense peaks in the low-angle region, with shoulder peaks showing an increase in sulphate loading from 10% to 30%. The BET-specific surface area for the pure KIT-6 supports measured at 1003 m2/g, indicative of a well-defined mesoporous structure. Thermogravimetric analysis (TGA) showed a two-stage weight loss, attributed to the elimination of hydrated water (about 200 °C) and decomposition of sulphate ions (400-450 °C). SEM analysis highlighted the surface morphology of the active SK-2 catalyst. Hydrocatalytic and catalytic cracking reactions were performed, and about 99.8% conversion was achieved with 20 mL/H H2 flow, whereas higher production of bioliquids was observed at a flow of 15 mL/h. The hydrocracking mechanism was also studied to understand the formation of lower hydrocarbons. GC analyses of simulated distilled gasoline, kerosene, and diesel showed diverse hydrocarbon compositions. For engine testing, non-hydrocracked fuel rose to 28 kW at 3000 rpm and declined to 21 kW at 3500 rpm. Emission analysis revealed decreasing trends in NOX emissions of hydrogen-rich blends, with values of 65 ppm, 54 ppm, and 48 ppm for petrol, NHBL, and HBL, respectively. Similarly, SO2 emissions reduced from petrol to NHBL and HBL at 910 ppm, 800 ppm, and 600 ppm, respectively, suggesting reduced environmental impact. CO emissions exhibited a substantial reduction in NHBL (0.90%) and HBL (0.54%) compared to petrol (2.70%), emphasizing the cleaner combustion characteristics. Our results provide a comprehensive exploration of waste chicken oil hydrocracking, emphasizing catalyst synthesis, fuel characterization, engine performance, and environmental impact, thereby contributing valuable insights to the field of sustainable bioenergy.

Heavy metal accumulation in root and shoot tapioca plant biomass grown in agriculture land situated around the magnesite mine tailings.

Heavy metal pollution in soil has emerged as a major environmental concern. This can be attributed to human activities such as mining, modern agriculture, and industrialization. This study was conducted to determine how heavy metals spread from mine tailings to surrounding farmland. Metal absorption and accumulation were also investigated in the root and shoot biomass of tapioca crops grown in those farmlands. Metal concentrations in MTAS1 were 85.3 ± 1.2, 45.8 ± 1.5, 134.8 ± 1.7, 92.4 ± 2.2, and 78.95 ± 1.4 mg kg-1, respectively. Heavy metal concentrations in MTAS2 and MTAS3 were found to be 79.62 ± 1.6, 75.4 ± 1.5, 41.31 ± 1.1, 47.8 ± 1.6, 142.5 ± 2.1, 128.4 ± 1.4, 86.2 ± 1.9, 79.5 ± 1.3, and 83.4 ± 1.2 mg kg-1, respectively. Tapioca crop shoot and root biomass grown at these metal polluted sites absorbed and accumulated significant amounts of Cd, Cu, Zn, Pb, Ni, and Mn. Notably, the metal content of the tapioca crop's root and shoot biomass exceeded national standards.

Phloridzin's Diabetic Wound Healing Potential through DPP-4 Enzyme Inhibition: A Review Article.

Diabetic wound healing is a dynamic medical process that takes place in an environment within the body that is complex and contains elevated sugar levels, oxygen deprivation, and cellular oxidative stress. Phloridzin (Phlorizin) is one of the most well-known polyphenols found in apples because of its anti-inflammatory, antioxidant, antibacterial, antidiabetic, and antiseptic properties; it can also play a significant part in the healing of diabetic wounds. The study aimed to investigate the role of phloridzin as an efficient DPP-4 inhibitor with additional therapeutic effects in diabetic wound healing, as Dipeptidyl Peptidase-4 (DPP-4) expression increases in response to increases in glucose, Reactive Oxygen Species (ROS), and inflammation. Phloridzin inhibiting DPP-4 preserves Stromal cell-derived Factor-1α (SDF-1α), Insulin-like Growth Factor (IGF), and Glucagon-like Peptide-1 (GLP-1), which are possible DPP-4 substrates involved in wound healing. The accessible material from systemic searches in PubMed, Scopus, and published articles was reviewed with no period of limitation. The in silico study showed strong binding of phloridzin with DPP-4 protein (2P8S); also, in vitro DPP-4 inhibition assay has shown better inhibition by phloridzin. This study offers new research directions for examining phloridzin's capacity to withstand oxidative stress, as well as for redefining its tactical function as a powerful DPP-4 inhibitor to regulate the process involved in the healing of diabetic wounds.

UV index-based model for predicting synthesis of (pre-)vitamin D3 in the mediterranean basin.

The importance of solar radiation for the body's ability to synthesize Vitamin D3 is well documented, yet the precise amount of sun exposure required to avoid Vitamin D insufficiency is less clear. To address this knowledge gap, this study sought to utilize the sun in a suitable period at the optimum dose by utilizing numerical simulations to determine the amount of Vitamin D3 synthesis in the skin according to season, time of day, and geographical location in Turkey. The study was carried out in three stages; in the first stage, daily, monthly, and annual values were determined in cases where the solar zenith angle has the active UV-B wavelength. The second stage determined the level of Vitamin D that can be synthesized in all skin types at 25% solar radiation exposure. In the third stage, the sun exposure time required for 1000 International Units (IU) for all skin types was calculated. According to the analysis, the yearly period of active synthesis of D3 on Earth lasts from the beginning of March to the third week of October. During the day, it is between 10:00 and 16:00. For 1000 IU/day, the average annual estimated times (minutes) are 5.05 for Type I, 6.3 for Type II, 7.6 for Type III, 11.35 for Type IV, 15.15 for Type V, and 25.25 for Type VI. The results of this paper will impact awareness for academic-medical users.

Assessment of antimicrobial, antidiabetic, and anti-inflammatory properties of acetone extract of Aerva lanata (L.) by in-vitro approach and bioactive compounds characterization.

The antimicrobial, antidiabetic, and anti-inflammatory activities efficiency of Aerva lanata plant extracts (aqueous (Aqu-E), acetone (Ace-E), and ethanol (Eth-E)) were investigated in this study. Furthermore, the active molecules exist in the crude extract were characterized by UV-Visible spectrophotometer, Fourier transform infrared (FTIR), High-performance liquid chromatography (HPLC), and Gas Chromatography-Mass Spectrometry (GC-MS) analyses. The preliminary phytochemical study revealed that the Ace-E restrain more phytochemicals like alkaloids, saponins, anthraquinone, tannins, phenolics, flavonoids, glycosides, terpenoids, amino acid, steroids, protein, coumarin, as well as quinine than Aqu-E and Eth-E. Accordingly to this Ace-E showed considerable antimicrobial activity as the follows: for bacteria S. aureus > E. coli > K. pneumoniae > P. aeruginosa > B. subtilis and for fungi T. viride > A.flavus > C. albicans > A.niger at 30 mg ml concentration. Similarly, Ace-E showed considerable antidiabetic (α-amylase: 71.7 % and α-glucosidase: 70.1 %) and moderate anti-inflammatory (59 % and 49.8 %) activities. The spectral and chromatogram studies confirmed that the Ace-E have pharmaceutically valuable bioactive molecules such as (Nbutyl)-octadecane, propynoic acid, neophytadiene, and 5,14-di (N-butyl)-octadecane. These findings suggest that Ace-E from A. lanata can be used to purify additional bioactive substances and conduct individual compound-based biomedical application research.

PDMS nanoparticles-decorated PDMS substrate promotes adhesion, proliferation and differentiation of skin cells.

Polydimethylsiloxane (PDMS) is known to be a common substrate for various cell culture-based applications. However, native PDMS is not very conducive for cell culture and hence, surface modification via cell adhesion moieties is generally needed to make it suitable especially for long-term cell culture. To address this issue, we propose to coat PDMS nanoparticles (NPs) on the surface of PDMS film to improve adhesion, proliferation and differentiation of skin cells. The proposed modification strategy introduces necessary nanotopography without altering the surface chemical properties of PDMS. Due to resemblance in the mechanical properties of PDMS with skin, PDMS NPs can recreate the native extracellular nanoenvironment of skin on the PDMS surface and provide anchoring sites for skin cells to adhere and grow. Human keratinocytes, representing 95% of the epidermal skin cells maintained their characteristic well-spread morphology with the formation of interconnected cell-sheets on this coated PDMS surface. Moreover, our in vitro immunofluorescence studies confirmed expression of distinctive epidermal protein markers on the coated surface indicating close resemblance with the native skin epidermis. Conclusively, our findings suggest that introducing nanotopography via PDMS NPs can be an effective strategy for emulating the native cellular functions of keratinocytes on PDMS based cell culture devices.

Mitigating microplastic pollution: A critical review on the effects, remediation, and utilization strategies of microplastics.

Microplastics are found ubiquitous in the natural environment and are an increasing source of worry for global health. Rapid industrialization and inappropriate plastic waste management in our daily lives have resulted in an increase in the amount of microplastics in the ecosystem. Microplastics that are <150 µm in size could be easily ingested by living beings and cause considerable toxicity. Microplastics can aggregate in living organisms and cause acute, chronic, carcinogenic, developmental, and genotoxic damage. As a result, a sustainable approach to reducing, reusing, and recycling plastic waste is required to manage microplastic pollution in the environment. However, there is still a significant lack of effective methods for managing these pollutants. As a result, the purpose of this review is to convey information on microplastic toxicity and management practices that may aid in the reduction of microplastic pollution. This review further insights on how plastic trash could be converted as value-added products, reducing the load of accumulating plastic wastes in the environment, and leading to a beneficial endeavor for humanity.

Projected decline in the strength of vegetation carbon sequestration under climate change in India.

Tropical vegetation plays a critical role in terrestrial carbon budget and supply many ecological functions such as carbon sequestration. In recent decades, India has witnessed an increase in net primary productivity (NPP), an important measure of carbon sequestration. However, uncertainties persist regarding the sustainability of these land carbon sinks in the face of climate change. The enhanced NPP is driven by the strong CO2 fertilization effect (CFE), but the temporal patterns of this feedback remain unclear. Using the carbon flux data from the Earth System Models (ESMs), an increasing trend in NPP was observed, with projections of NPP to 2.00 ± 0.12 PgCyr-1 (25 % increase) during 2021-2049, 2.36 ± 0.12 PgCyr-1 (18 % increase) during 2050-2079, and 2.67 ± 0.07 PgCyr-1 (13 % increase) during 2080-2099 in Indian vegetation under SSP585 scenario. This suggests a significant decline in the NPP growth rate. To understand the feedback mechanisms driving NPP, the relative effects of CFE and warming were analyzed. Comparing simulations from the biogeochemically coupled model (BGC) with the fully coupled model, the BGC model projected a 74.7 % increase in NPP, significantly higher than the 55.9 % increase projected by the fully coupled model by the end of the century. This indicates that the consistent increase in NPP was associated with CO2 fertilization. More importantly, results reveal that the decrease in the NPP growth rate was due to the declining contribution of CFE at a rate of -0.62 % per 100 ppm CO2 increase. This decline could be attributed to factors such as nutrient limitations and high temperatures. Additionally, significant shifts in the strength of carbon sinks in offsetting the CO2 emissions were identified, decreasing at a rate of -1.15 % per decade. This decline in the strength of vegetation carbon sequestration may increase the societal dependence on mitigation measures to address climate change.

Sugar cane bagasse hydrolysate (SBH) as a lucrative carbon supplement to upgrade the lipid and fatty acid production in Chlorococcum sp. for biodiesel through an optimized binary solvent system.

Cost is the crucial impediment in commercializing microalgal biodiesel. Therefore, cultivating microalgae in cost-effective nutrients reduces the upstream process cost remarkably. Thus, in this study, sugar cane bagasse hydrolysate (SBH) as a lucrative carbon supplement for Chlorococcum sp. and subsequent lipid extraction via an optimized solvent system for biodiesel production was investigated. Characterization of SBH revealed the presence of various monosaccharides and other sugar derivatives such as glucose, fructose, xylose, arabinose, etc. The maximum dry cell weight of 1.7 g/L was estimated in cultures grown in 10 mL SBH. Different solvents such as diethyl ether (DEE), chloroform (CHL), ethyl acetate (ETA), hexane (HEX), methanol (MET), ethanol (ETOH), acetone (ACE) and also combination of solvents (2:1 ratio) such as DEE: MET, CHL: MET, HEX: MET, HEX: ETOH was tested for lipid extraction efficacy. Among solvents used, 12.3% and 18.4% of lipids were extracted using CHL and CHL: MET, respectively, from 10 mL SBH amended cultures. However, the biodiesel yield was found to be similar at about 70.16 % in both SBH and no SBH-added cultures. The fatty acid profile of the biodiesel shows palmitic, oleic, linoleic, linolenic, and arachidonic acid as principal fatty acids. Further, the levels of SFAs, MUFAs, and PUFAs in 10 mL SBH-added cells were 24.67, 12.89, and 34.24%, respectively. Eventually, the fuel properties of Chlorococcum sp. biodiesel, satisfying international biodiesel standards, make the biodiesel a viable diesel substitute in the future.

Predictive value of the thrombotic risk criteria proposed in the 2023 ESC guidelines for the management of ACS: insights from a large PCI registry.

AIM: To assess the value of the thrombotic risk criteria proposed in the 2023 guidelines of the European Society of Cardiology (ESC) for the management of acute coronary syndrome (ACS) to predict the ischaemic risk after percutaneous coronary intervention (PCI). METHODS AND RESULTS: Consecutive patients with acute or chronic coronary syndrome undergoing PCI at a large tertiary-care center from 2014 to 2019 were included. Patients were stratified into low, moderate, or high thrombotic risk based on the ESC criteria. The primary endpoint was major adverse cardiovascular events (MACEs) at 1 year, a composite of all-cause death, myocardial infarction (MI), and stroke. Secondary endpoints included major bleeding. Among 11 787 patients, 2641 (22.4%) were at low-risk, 5286 (44.8%) at moderate risk, and 3860 (32.7%) at high-risk. There was an incremental risk of MACE at 1 year in patients at moderate (hazard ratios (HR) 2.53, 95% confidence interval (CI) 1.78-3.58) and high-risk (HR 3.39, 95% CI 2.39-4.80) as compared to those at low-risk, due to higher rates of all-cause death and MI. Major bleeding rates were increased in high-risk patients (HR 1.59, 95% CI 1.25-2.02), but similar between the moderate and low-risk group. The Harrell's C-index for MACE was 0.60. CONCLUSION: The thrombotic risk criteria of the 2023 ESC guidelines for ACS enable to stratify patients undergoing PCI in categories with an incremental 1 year risk of MACE; however, their overall predictive ability for MACE is modest. Future studies should confirm the value of these criteria to identify patients benefiting from an extended treatment with a second antithrombotic agent.

Macrocyclic Sulfur Ligand Stabilized Trans-Palladium Dichloride Complex: Syntheses, Structure, Chlorine Rotation, and Application in α-Olefination of Nitriles by Primary Alcohols.

Herein, we have reported the synthesis of a macrocyclic organosulfur ligand (L1) having a seventeen-membered macrocyclic ring. Subsequently, the corresponding trans-palladium complex (C1) of bulky macrocyclic organosulfur ligand (L1) was synthesized by reacting it with PdCl2 (CH3 CN)2 salt. The newly synthesized ligand and complex were characterized using various analytical and spectroscopic techniques. The complex showed a square planar geometry with trans orientation of two ligands around the palladium center. The complex possesses intramolecular SCH…Cl interactions of 2.648 Šbetween the macrocyclic ligand and palladium dichloride. The potential energy surface (PES) for the rotational process of C1 suggested a barrier of ~23.81 kcal/mol for chlorine rotation. Furthermore, the bulky macrocyclic organosulfur ligand stabilized palladium complex (C1) was used as a catalyst (2.5 mol %) for α-olefination of nitriles by primary alcohols. The α,ß-unsaturated nitrile compounds were found to be the major product of the reaction (57-78 % yield) with broad substrate scope and large functional group tolerance. Notably, the saturated nitrile product was not observed during the reaction. The mechanistic studies suggested the formation of H2 and H2 O as only by-products of the reaction, thereby making the protocol greener and sustainable.

Pharmacoscreening, molecular dynamics, and quantum mechanics of inermin from Panax ginseng: a crucial molecule inhibiting exosomal protein target associated with coronary artery disease progression.

Background: Exosomes, microvesicles, carry and release several vital molecules across cells, tissues, and organs. Epicardial adipose tissue exosomes are critical in the development and progression of coronary artery disease (CAD). It is hypothesized that exosomes may transport causative molecules from inflamed tissue and deliver to the target tissue and progress CAD. Thus, identifying and inhibiting the CAD-associated proteins that are being transported to other cells via exosomes will help slow the progression of CAD. Methods: This study uses a systems biological approach that integrates differential gene expression in the CAD, exosomal cargo assessment, protein network construction, and functional enrichment to identify the crucial exosomal cargo protein target. Meanwhile, absorption, distribution, metabolism, and excretion (ADME) screening of Panax ginseng-derived compounds was conducted and then docked against the protein target to identify potential inhibitors and then subjected to molecular dynamics simulation (MDS) to understand the behavior of the protein-ligand complex till 100 nanoseconds. Finally, density functional theory (DFT) calculation was performed on the ligand with the highest affinity with the target. Results: Through the systems biological approach, Mothers against decapentaplegic homolog 2 protein (SMAD2) was determined as a potential target that linked with PI3K-Akt signaling, Ubiquitin mediated proteolysis, and the focal adhesion pathway. Further, screening of 190 Panax ginseng compounds, 27 showed drug-likeness properties. Inermin, a phytochemical showed good docking with -5.02 kcal/mol and achieved stability confirmation with SMAD2 based on MDS when compared to the known CAD drugs. Additionally, DFT analysis of inermin showed high chemical activity that significantly contributes to effective target binding. Overall, our computational study suggests that inermin could act against SMAD2 and may aid in the management of CAD.