Aims Obesity is commonly hypothesized to lead to the development of heart failure (HF) in part due to increases in blood volume (BV) and left ventricular (LV) remodelling. Whether adiposity and obesity severity are associated with BV expansion and subsequent LV remodelling in middle‐aged individuals at increased risk (IR) prior to the onset of HF is unknown. Methods and results We analysed data from 96 middle‐aged (40–64 years) non‐obese (25.8 [23.6–28.6] kg/m 2 ) controls (CON) and 126 IR middle‐aged adults (elevated cardiac biomarkers plus established risk factors). IR adults were stratified based upon body mass index class: (1) <30 kg/m 2 , IR Non‐Obese ( n = 28, 28.2 [24.6–29.9] kg/m 2 ); (2) Class I >30–35 kg/m 2 , IR Class‐I ( n = 39, 33 [31.9–33.6] kg/m 2 ); and, (3) Class II/III >35 kg/m 2 , IR Class‐II/IIII ( n = 59, 41.2 [37.1–43.8] kg/m 2 ). BV (carbon monoxide rebreathing), body composition (hydrodensitometry or dual‐energy X‐ray absorptiometry), and LV structure and function (echocardiography) were assessed. Fat mass was independently associated with BV ( β = 0.17, p < 0.001) which was independently associated with LV end‐diastolic volume (LVEDV) index ( β = 0.54, p < 0.001). BV was lower in CON (5046 ± 1123 ml) than all IR groups (IR Non‐Obese : 5622 ± 1137; IR Class‐I : 6033 ± 1237; IR Class‐II/III : 6548 ± 1153 mL; all p < 0.05). IR Class‐II/III had greater erythrocyte volume compared to CON ( p < 0.005), even after normalization to fat‐free mass (CON: 36.2 ± 4.6; IR Class‐II/III : 39.9 ± 5.1 ml/kg fat‐free mass; p < 0.001). Only IR Class‐II/III had an enlarged LV end‐diastolic volume when normalized to body surface area compared to both CON and IR Non‐Obese (both, p < 0.05). Conclusions While lean mass is the primary determinant of BV, fat mass is independently associated with BV expansion and larger LVEDV. IR adults with class II/III obesity display distinct LV enlargement that is disproportionate to body size (i.e. LVEDV index) and may represent a physiologically distinct subgroup of obesity as opposed to a simple continuum of disease severity.
ABSTRACT The complement system bridges innate and adaptive immunity, and its role in the tumor microenvironment (TME) is complex and context‐dependent. Multiple recent studies have demonstrated the complement system's pro‐ and anti‐tumor effects. In the present review, we discuss the role of complement in shaping the functions of various immune cells, including T cells, macrophages, natural killer (NK) cells, neutrophils, and dendritic cells within the TME. We also highlighted how complement proteins drive the pro‐ or anti‐inflammatory immune responses, the associated cellular and molecular mechanisms, their influence on anti‐tumor immunity, and some clinical trials targeting complement systems. A comprehensive and critical understanding of the complement system in oncoimmunology may aid in designing effective tumor‐specific therapeutic strategies.
γ‐Keto sulfones, despite being a medicinally relevant building block, have never been integrated with the bioactive oxindole scaffold present in several alkaloid natural products. On the other hand, strategies involving SO 2 capture in organic molecules to access value‐added products are gaining momentum. Therefore, a strategy en route to γ‐keto alkylsulfonylated oxindoles bearing a β ‐all‐carbon quaternary center is disclosed. Toward this goal, the bisfunctionalization of N‐(hetero)arylacrylamides has been realized via the strain‐release driven ring‐scission of strained 3°‐cyclopropanols in the presence of DABSO under visible‐light photoredox catalysis to access a library of γ‐keto alkylsulfonylated oxindoles. Also, the aromaticity‐driven bond‐scission in pro‐aromatics like 4‐alkyl‐1,4‐DHPs in the presence of Na 2 S 2 O 5 under visible‐light photoredox catalysis has been exploited to trigger the alkylsulfonylative‐arylation of N‐(hetero)arylacrylamides to access a library of alkylsulfonylated oxindoles featuring a β‐all‐carbon quaternary center. Broad substrate scope is demonstrated, and the mechanistic probing studies have been complemented with DFT calculations. Also, moderate to potent cytotoxic activity is observed against the tested triple‐negative breast cancer cell lines for some of the synthesized sulfonylated oxindole derivatives. Further, evaluation of the mechanism of cell death for the most potent oxindole analog revealed that it induces apoptosis in a concentration‐dependent manner.
The Front Cover depicts a relaxing spa treatment offered to a strained cyclopropanol client. The sunlight coming through the window symbolizes how visible light is essential for therapy, and photocatalysts (PC) and key intermediates engaged in the strain‐release of cyclopropanol are depicted as spa therapists. The bottle of essential oil illustrates the use of DABSO as the essential source of SO 2 gas. The PC therapist′s scissors chop off the radical from the dihydropyridine for SO 2 capture and subsequent reaction with the acrylamide bed, eventually yielding SVI oxindoles. More information on this photoredox strategy can be found in the Research Article by T. Khan and co‐workers (DOI: 10.1002/ejoc.202500726 ). Bhavik Parve is acknowledged for the graphic.
Abstract The bacterial reverse mutation test is essential for identifying the mutagenic potential of chemicals. The solubility of the test substance is vital for achieving the recommended assay concentration. Preferred solvents like dimethyl sulfoxide and water are chosen for their compatibility and historical data. Selecting a compatible solvent with Salmonella typhimurium and Escherichia coli WP2 uvrA strains, considering a maximum cytotoxic concentration or the limit of 5 mg/plate, can be challenging. This study assessed various solvents, including N,N‐dimethylformamide, acetone, acetonitrile, ethyl acetate, 95% ethanol, diethylene glycol monomethyl ether, methanol, P‐dioxane, tetrahydrofuran, and dimethylacetamide, as alternative solvents in the AMES test. Results showed all solvents, except tetrahydrofuran, were compatible at concentrations up to 100 μL/plate or more, as they did not inhibit S9 enzymes, bacterial growth, or alter bacterial revertant colony counts, making them suitable for the bacterial reverse mutation test.
ABSTRACT The Ames test is a fundamental assay for evaluating chemical mutagenicity, particularly for nitrosamines, which are widespread environmental and pharmaceutical contaminants. To improve sensitivity, regulatory agencies have endorsed the enhanced Ames test (EAT), which incorporates five tester strains, a 30‐min pre‐incubation step, and metabolic activation using both rat and hamster liver S9 fractions. While Salmonella typhimurium TA102 is known for its sensitivity to oxidative mutagens, its performance under EAT conditions has not been fully characterized. This study evaluated the mutagenic response of TA102 using two nitrosamine positive controls: N ‐nitrosodimethylamine (NDMA) and 1‐cyclopentyl‐4‐nitrosopiperazine (CPNP). E. coli WP2 uvr A(pKM101) showed consistent mutagenic responses to both NDMA and CPNP, consistent with existing EAT data. TA102 demonstrated a robust response to NDMA but not to CPNP, suggesting limited sensitivity to certain nitrosamines. These findings support the continued use of WP2 uvr A(pKM101) in EAT protocols and highlight the limited utility of TA102 for comprehensive nitrosamine mutagenicity assessment.
ABSTRACT With rising temperatures and increasing power demands, microgrid failures have become frequent, highlighting the need for effective energy management. Microgrids, particularly those integrating renewable energy sources (RES), are gaining traction as decentralized energy solutions. Despite their potential, Photovoltaic (PV) systems face challenges due to the intermittent nature of solar energy, necessitating energy storage solutions to maintain a stable power supply. Battery energy storage systems (BESS) are critical in buffering power fluctuations and enhancing grid stability, forming PV‐battery hybrid microgrids capable of operating in both grid‐connected and islanded modes. This study focuses on optimizing the management of BESS within a solar‐integrated microgrid over 24 h to improve energy efficiency and cost‐effectiveness. Additionally, the study examines the implementation of demand response (DR) techniques, including peak clipping, valley filling, and load shifting, to further enhance grid stability and economic benefits. Using MATLAB for simulations, the study employs state flow study and linear programming methods. Results indicate that the energy management system (EMS) using particle swarm optimization (PSO) enhances the efficiency of EMS using linear programming (LP). Simulation results conducted using MATLAB R2023b indicate that PSO outperforms LP in minimizing daily electricity costs (up to 15.32% savings), stabilizing state of charge (SoC), and reducing grid power fluctuations. These findings underscore the importance of advanced EMS in enhancing microgrid efficiency, particularly under variable weather conditions. This research underscores the crucial role of energy management systems (EMS) in enhancing the reliability and sustainability of microgrids, particularly in rural and underdeveloped areas. By optimizing the charge and discharge cycles of BESS based on load requirements and implementing DR strategies, the proposed methods demonstrate substantial improvements in system performance and economic benefits.
Metal–organic frameworks (MOFs) have emerged as a transformative class of materials in materials science and chemistry due to their exceptional porosity and structural tunability. Composed of metal ions or clusters intricately coordinated with organic ligands, MOFs form highly ordered 3D networks with well‐defined pores and channels. These unique characteristics enable precise customization of pore size, shape, and functionality through the selection of appropriate metal ions and ligands, unlocking diverse applications across multiple fields. This review provides a comprehensive exploration of MOFs, focusing on their synthesis, structural properties, and versatility. Key areas of discussion include MOFs’ potential for catalytic activity, gas storage, sensing, and drug delivery. Of particular importance is their transformative role in environmental remediation, energy storage, and biomedical applications, demonstrating their adaptability to modern challenges. However, significant barriers such as scalability, long‐term stability, and economic viability must be addressed to enable widespread adoption. By detailing state‐of‐the‐art advancements, this review highlights MOFs’ unparalleled ability to achieve precision and efficiency in targeted applications, offering valuable insights for emerging researchers. The findings underscore MOFs’ pivotal role in addressing contemporary scientific and industrial challenges, paving the way for innovative solutions in energy, environment, and health.
Abstract Objective Due to the conflicting evidence and expected regional therapeutic variations for cost‐effectiveness in children with infantile epileptic spasms syndrome (IESS), this study assessed treatment effectiveness, safety, Health‐Related Quality of Life (HRQoL), and performed a cost‐effectiveness analysis (CEA) for hormonal therapies in Indian children with IESS. Methods This prospective observational study was conducted at a referral pediatrics center in North India. Children with IESS (aged 3–18 months), who were prescribed either a synthetic form of adrenocorticotrophic hormone (ACTH) or oral prednisolone, were included and compared for cessation of epileptic spasms (ES), treatment‐emergent adverse events (TEAEs), HRQoL (assessed through Hi‐QUALIN), and cost‐effectiveness using a decision‐tree model. Incremental cost effectiveness ratio (ICER) and number needed to treat were calculated. One‐way sensitivity analyses predicted the impact of each variable on the cost‐effectiveness (CE) model using a Tornado diagram. Results Of 93 children with IESS [73 (79%) boys; mean age (SD) = 10.1 (3.7) months; median (IQR) daily burden of ES: 27.8 (14.0, 61.9)], 55 (59%) were initiated on ACTH, while the rest on oral prednisolone (38 [41%]). After 2 weeks of treatment, ES cessation was achieved in 29/55 (53%) on ACTH and 13/38 (34%) on oral prednisolone. Additionally, an insignificantly different incidence of TEAEs was reported in the ACTH group (23/55 [42%]) compared with the oral prednisolone group (19/38 [50%]). Children aged 3–12 months showed statistically significant improvement in overall HRQoL scores at 2 weeks of treatment ( p < 0.01). Using a decision tree model, CEA showed higher ICER (ICER: 122 185 INR; ~1468.90 USD and QALY: 331 643 INR; ~3987.0 USD) for ACTH than oral prednisolone, suggesting caregiver or parents need to spend at least 122 185 INR for one in five children on ACTH to be ES free compared with prednisolone. Significance This analysis suggests ACTH was more cost‐effective than oral prednisolone for managing IESS from the Indian patient's perspective. ACTH was also a cost‐effective option for short‐term quality of life outcomes. Plain Language Summary This study looked at two first‐line treatment options, that is, ACTH and oral prednisolone, for infantile epileptic spasms syndrome (IESS) at a referral pediatric center in North India. We found that ACTH was more effective than oral prednisolone for epileptic spasm cessation and improved health‐related quality of life in the short term. Although ACTH costs more, it was found to be a cost‐effective option. These findings can help families and clinicians make better treatment choices based on both health benefits and costs.