Mechanistic Insights Research Articles

Disruptive compensatory mechanisms in fibromyalgia syndrome and their association with pharmacological agents.

Fibromyalgia syndrome (FMS) is a chronic disorder characterized commonly by widespread musculoskeletal pain and fatigue, predominantly affecting women, with its complexity often leading to underdiagnosis and complicating treatment effectiveness. Transcranial magnetic stimulation (TMS) metrics are potential markers to optimize FMS treatments; however, evidence is limited. Our study aimed to explore the relationship between cortical excitability and inhibition, assessed through TMS markers, and clinical characteristics in patients with FMS. This presented cross-sectional study employed baseline data from a clinical trial with 108 FMS patients, mostly female (88.8%), and mean age of 47.3 years old (SD = 12.06). Our analysis showed that decreased short-intracortical inhibition (SICI) was associated with gabapentinoids use, nicotine history, and increased fatigue levels, suggesting its connection with compensatory mechanisms for non-painful FMS features. Increased motor intracortical facilitation (ICF) was linked with greater pain severity and shorter FMS duration, implying its relationship with a reorganization of sensorimotor pathways due to chronic pain. Additionally, higher resting motor threshold (rMT) was associated with less effective pain modulation (lower conditioned pain modulation [CPM]), indicating a disruption of pain compensatory mechanism. Given the role of SICI in indexing homeostatic brain mechanisms and its association with fatigue, a hallmark characteristic of FMS-induced behavioral changes, these results suggest that FMS likely has a deleterious effect on brain inhibitory function, thus providing a potential novel insight for FMS mechanisms. In addition, it seems that this compensatory mechanism's disruption is enhanced by pharmacological agents such as gabapentioids and nicotine.

Coarse-Graining the Recognition of a Glycolipid by the C-Type Lectin Mincle Receptor.

Macrophage inducible Ca2+-dependent lectin (Mincle) receptor recognizes Mycobacterium tuberculosis glycolipids to trigger an immune response. This host membrane receptor is thus a key player in the modulation of the immune response to infection by M. tuberculosis and has emerged as a promising target for the development of new vaccines against tuberculosis. The recent development of the Martini 3 force field for coarse-grained (CG) molecular modeling allows the study of interactions of soluble proteins with small ligands which was not typically modeled well with the previous Martini 2 model. Here, we present a refined approach detailing a protocol for modeling interactions between a glycolipid and its receptor at a CG level using the Martini 3 force field. Using this approach, we studied Mincle and identified critical parameters governing ligand recognition, such as loop flexibility and the regulation of hydrophobic groove formation by calcium ions. In addition, we assessed ligand affinity using free energy perturbation calculations. Our results offer mechanistic insight into the interactions between Mincle and glycolipids, providing a basis for the rational design of molecules targeting this type of membrane receptors.

Ionomer and Membrane Designs for Low-Temperature CO2 and CO Electrolysis.

Low-temperature electroreduction of CO2 and CO (CO(2)RR) into valuable chemicals and fuels offers a promising pathway to reduce greenhouse gas emissions and achieve carbon neutrality. Today's low-temperature CO(2)RR technology relies on the use of ionomers, polymers with ionized groups, primarily as catalyst layer (CL) additives. In the meantime, ionomers can assemble into ion-exchange membranes (IEMs), serving as important components of electrolyzers. According to the ion-exchange functions, ionomer additives are classified as cation-exchange ionomers (CEIs) and anion-exchange ionomers (AEIs); similarly, IEMs are divided into cation-exchange membranes (CEMs) and anion-exchange membranes (AEMs), as well as the multilayer polymer electrolytes (MPEs). Recent studies show that ionomer additives can regulate the catalytic microenvironment and thereby enhance performance towards desired products. This Review discusses the roles of ionomer additives and IEMs in CO2 and CO reduction reactions, highlighting the latest mechanistic insights and performance advances. It outlines challenges in designing ionomer additives and IEMs to improve product selectivity, energy efficiency (EE), and operational lifetime of CO(2)RR electrolyzers, while also providing perspectives on future research directions. The aim is to connect the current status of ionomer and membrane development with performance metrics analysis, offering insights for the advancement of commercially relevant low-temperature CO(2)RR electrolyzers.

Viral-bacterial co-infections screen in vitro reveals molecular processes affecting pathogen proliferation and host cell viability.

The broadening of accessible methodologies has enabled mechanistic insights into single-pathogen infections, yet the molecular mechanisms underlying co-infections remain largely elusive, despite their clinical frequency and relevance, generally exacerbating symptom severity and fatality. Here, we describe an unbiased in vitro screening of pairwise co-infections in a murine macrophage model, quantifying pathogen proliferation and host cell death in parallel over time. The screen revealed that the majority of interactions are antagonistic for both metrics, highlighting general patterns depending on the pathogen virulence strategy. We subsequently decipher two distinct molecular interaction points: Firstly, murine Adenovirus 3 modifies ASC-dependent inflammasome responses in murine macrophages, altering host cell death and cytokine production, thereby impacting secondary Salmonella infection. Secondly, murine Adenovirus 2 infection triggers upregulation of Mprip, a crucial mediator of phagocytosis, which in turn causes increased Yersinia uptake, specifically in virus pre-infected bone-marrow-derived macrophages. This work therefore encompasses both a first-of-its-kind systematic assessment of host-pathogen-pathogen interactions, and mechanistic insight into molecular mediators during co-infection.

AI-based modeling studies for dye removal using mixed biomass composites from algae and plant seeds: Isotherm, kinetics, and mechanistic insights

Biomass based remediation have emerged as a promising solution for the economic and sustainable pollutant removal from environment. In this study, novel mixed biomass derived from algae and manila tamarind seeds was synthesized and extensively characterized for application in dye adsorption. Mesoporous structure with pore diameter of 4.006 nm was observed from Brunauer-Emmett-Teller (BET) characterization. Best fit for isotherm was identified with Langmuir model indicating the monolayer nature of dye removal. Artificial intelligence (AI) based models – artificial neural network (ANN) and adaptive neuro fuzzy interference (ANFIS) system were employed for the prediction of dye removal under different conditions, a unique approach which has not been explored in previous studies based on mixed biomass adsorption. In addition, embedding particle swarm optimization (PSO) had a significant improvement in prediction of dye removal. For both Eriochrome black (EB) dye and Brilliant Orange (BO) dye adsorption employing mixed biomass, the ANN-PSO model yielded the best correlation of 0.9999 and 0.9994. For eriochrome black and brilliant orange dye, the maximum adsorption of 79.95 mg/g and 102.4 mg/g for the mixed biomass composite was noted, highlighting the adsorption efficiency of biomass. The uniqueness of the study lies in the integration of mixed biomass adsorption with AI driven modeling, providing a dual approach to enhance dye removal and adsorption efficiency. In addition, the regenerated mixed biomass can be reused for five consecutive cycles, highlighting its practical application, distinguishing from existing research that focused on single use biomass systems.

Calcium Hydroxylapatite in Regenerative Aesthetics: Mechanistic Insights and Mode of Action.

Calcium Hydroxylapatite-Carboxymethylcellulose (CaHA-CMC) is a widely used soft-tissue filler known for its compatibility with human tissue and for its effective volumizing properties. The biodegradable CaHA microspheres function as a scaffold for the formation of new tissue by stimulating a variety of cellular responses leading to the production of collagen, elastin, vasculature and proteoglycans and thereby enhancing skin quality. Despite the promising regenerative effects of CaHA-CMC, substantial gaps remain in understanding its precise underlying mechanisms, and addressing these gaps is crucial for optimizing its clinical applications. A literature search was conducted using PubMed, google scholar and web of science for key words including "calcium hydroxylapatite", " tissue regeneration", "macrophages", "fibroblasts" and "calcium". This review elucidates the novel mechanisms of CaHA-CMC action within aesthetic medicine, with a focus on the dynamic interactions between macrophages and fibroblasts. The key role of calcium ions as critical biocues in directing skin regeneration pathways is explored alongside an examination of the distinct physicochemical properties of CaHA-CMC. CaHA-CMC helps in tissue regeneration by providing calcium ions that act as key biological cues, promoting fibroblast activity and collagen production.

Emerging ZnO Semiconductors for Photocatalytic CO2 Reduction to Methanol.

Carbon recycling is poised to emerge as a prominent trend for mitigating severe climate change and meeting the rising demand for energy. Converting carbon dioxide (CO2) into green energy and valuable feedstocks through photocatalytic CO2 reduction (PCCR) offers a promising solution to global warming and energy needs. Among all semiconductors, zinc oxide (ZnO) has garnered considerable interest due to its ecofriendly nature, biocompatibility, abundance, exceptional semiconducting and optical properties, cost-effectiveness, easy synthesis, and durability. This review thoroughly discusses recent advances in mechanistic insights, fundamental principles, experimental parameters, and modulation of ZnO catalysts for direct PCCR to C1 products (methanol). Various ZnO modification techniques are explored, including atomic size regulation, synthesis strategies, morphology manipulation, doping with cocatalysts, defect engineering, incorporation of plasmonic metals, and single atom modulation to boost its photocatalytic performance. Additionally, the review highlights the importance of photoreactor design, reactor types, geometries, operating modes, and phases. Future research endeavors should prioritize the development of cost-effective catalyst immobilization methods for solid-liquid separation and catalyst recycling, while emphasizing the use of abundant and non-toxic materials to ensure environmental sustainability and economic viability. Finally, the review outlines key challenges and proposes novel directions for further enhancing ZnO-based photocatalytic CO2 conversion processes.

Base-excision repair pathway regulates transcription-replication conflicts in pancreatic ductal adenocarcinoma

Oncogenic mutations (such as in KRAS) can dysregulate transcription and replication, leading to transcription-replication conflicts (TRCs). Here, we demonstrate that TRCs are enriched in human pancreatic ductal adenocarcinoma (PDAC) compared to other common solid tumors or normal cells. Several orthogonal approaches demonstrated that TRCs are oncogene dependent. A small interfering RNA (siRNA) screen identified several factors in the base-excision repair (BER) pathway as main regulators of TRCs in PDAC cells. Inhibitors of BER pathway (methoxyamine and CRT) enhanced TRCs. Mechanistically, BER pathway inhibition severely altered RNA polymerase II (RNAPII) and R-loop dynamics at nascent DNA, causing RNAPII trapping and contributing to enhanced TRCs. The ensuing DNA damage activated the ATR-Chk1 pathway. Co-treatment with ATR inhibitor (VX970) and BER inhibitor (methoxyamine) at clinically relevant doses synergistically enhanced DNA damage and reduced cell proliferation in PDAC cells. The study provides mechanistic insights into the regulation of TRCs in PDAC by the BER pathway, which has biologic and therapeutic implications.

Can Foot Orthoses Benefit Symptomatic Runners? Mechanistic and Clinical Insights Through a Scoping Review.

Running is a widely practiced sport worldwide associated with a host of benefits on cardiovascular, metabolic, musculoskeletal, and mental health, but often leads to musculoskeletal overuse injuries. The prescription of a foot orthosis (FO) is common to manage musculoskeletal impairments during physical activity or functional tasks. Although FOs are frequently prescribed by clinicians for symptomatic populations of runners, the existing literature supporting the prescription of FOs in runners has predominantly focused on either uninjured individuals or a mix of uninjured and symptomatic populations. Thus, the effects of FOs on the treatment and/or prevention of overuse running injuries need to be investigated to guide future research and assist clinicians in their decision-making process. This scoping review aimed to evaluate the immediate and long-term effects of FOs on lower limb biomechanics, neuromuscular parameters, and pain and disability in symptomatic runners, and to identify factors that may influence the effects of FOs. Five databases (CINAHL, SPORTDiscus, MEDLINE, Embase, and Web of Science) were searched, resulting in 2536 studies. A total of 30 studies, published between 1992 and 2023 (730 symptomatic runners), were included following the removal of duplicates and the screening process. Wearing FOs while running is related to an immediate and a long-term decrease in pain and symptoms of overuse running injuries. Also, wearing FOs while running decreases eversion at the foot/ankle complex, leads to a more lateral plantar pressure at the heel and forefoot, and may change running motor control strategies. Finally, the effectiveness of FOs is influenced by its added features. This study provides recommendations for future research such as the need for standardized methods in describing FOs, considering participant characteristics such as foot morphology, and comparing different types of FOs. Also, this scoping review provides valuable insights for guiding the prescription and design of FOs, and suggests that integrating FOs into a comprehensive treatment plan may yield better results than standalone first-line treatments. Nonetheless, this scoping review highlights the need for future research to explore the optimal integration of FOs into injury-specific treatment plans.

A pathogen effector co-opts a host RabGAP protein to remodel pathogen interface and subvert defense-related secretion.

Pathogens have evolved sophisticated mechanisms to manipulate host cell membrane dynamics, a crucial adaptation to survive in hostile environments shaped by innate immune responses. Plant-derived membrane interfaces, engulfing invasive hyphal projections of fungal and oomycete pathogens, are prominent junctures dictating infection outcomes. Understanding how pathogens transform these host-pathogen interfaces to their advantage remains a key biological question. Here, we identified a conserved effector, secreted by plant pathogenic oomycetes, that co-opts a host Rab GTPase-activating protein (RabGAP), TOPGAP, to remodel the host-pathogen interface. The effector, PiE354, hijacks TOPGAP as a susceptibility factor to usurp its GAP activity on Rab8a, a key Rab GTPase crucial for defense-related secretion. By hijacking TOPGAP, PiE354 purges Rab8a from the plasma membrane, diverting Rab8a-mediated immune trafficking away from the pathogen interface. This mechanism signifies an uncanny evolutionary adaptation of a pathogen effector in co-opting a host regulatory component to subvert defense-related secretion, thereby providing unprecedented mechanistic insights into the reprogramming of host membrane dynamics by pathogens.

Visceral adiposity in postmenopausal women is associated with a pro-inflammatory gut microbiome and immunogenic metabolic endotoxemia.

Obesity, and in particular abdominal obesity, is associated with an increased risk of developing a variety of chronic diseases. Obesity, aging, and menopause are each associated with differential shifts in the gut microbiome. Obesity causes chronic low-grade inflammation due to increased lipopolysaccharide (LPS) levels which is termed "metabolic endotoxemia." We examined the association of visceral adiposity tissue (VAT) area, circulating endotoxemia markers, and the gut bacterial microbiome in a cohort of aged postmenopausal women. Fifty postmenopausal women (mean age 78.8 ± 5.3years) who had existing adipose measurements via dual x-ray absorptiometry (DXA) were selected from the extremes of VAT: n = 25 with low VAT area (45.6 ± 12.5 cm2) and n = 25 with high VAT area (177.5 ± 31.3 cm2). Dietary intake used to estimate the Healthy Eating Index (HEI) score was assessed with a food frequency questionnaire. Plasma LPS, LPS-binding protein (LBP), anti-LPS antibodies, anti-flagellin antibodies, and anti-lipoteichoic acid (LTA) antibodies were measured by ELISA. Metagenomic sequencing was performed on fecal DNA. Female C57BL/6 mice consuming a high-fat or low-fat diet were treated with 0.4mg/kg diet-derived fecal isolated LPS modeling metabolic endotoxemia, and metabolic outcomes were measured after 6weeks. Women in the high VAT group showed increased Proteobacteria abundance and a lower Firmicutes/Bacteroidetes ratio. Plasma LBP concentration was positively associated with VAT area. Plasma anti-LPS, anti-LTA, and anti-flagellin IgA antibodies were significantly correlated with adiposity measurements. Women with high VAT showed significantly elevated LPS-expressing bacteria compared to low VAT women. Gut bacterial species that showed significant associations with both adiposity and inflammation (anti-LPS IgA and LBP) were Proteobacteria (Escherichia coli, Shigella spp., and Klebsiella spp.) and Veillonella atypica. Healthy eating index (HEI) scores negatively correlated with % body fat and anti-LPS IgA antibodies levels. Preclinical murine model showed that high-fat diet-fed mice administered a low-fat diet fecal-derived LPS displayed reduced body weight, decreased % body fat, and improved glucose tolerance test parameters when compared with saline-injected or high-fat diet fecal-derived LPS-treated groups consuming a high-fat diet. Increased VAT in postmenopausal women is associated with elevated gut Proteobacteria abundance and immunogenic metabolic endotoxemia markers. Low-fat diet-derived fecal-isolated LPS improved metabolic parameters in high-fat diet-fed mice giving mechanistic insights into potential pro-health signaling mediated by under-acylated LPS isoforms. Video Abstract.

N-terminal domain homologs of the orange carotenoid protein increase quenching of cyanobacterial phycobilisomes.

Stress exerted by excess captured light energy in cyanobacteria is prevented by the photoprotective activity of the orange carotenoid protein (OCP). Under high light, the OCP converts from an orange, inactive form (OCPO) into the red form (OCPR) that binds to and quenches the phycobilisome (PBS). Structurally, the OCP consists of two domains: the N-terminal effector domain and a C-terminal regulatory domain. Structural analysis of the OCP-PBS complex showed that the N-terminal domains of an OCP dimer interact with the PBS core. These N-terminal OCP domains have single domain protein paralogs known as Helical Carotenoid Proteins (HCPs). Using phycobilisome quenching assays, we show that the HCP4 and HCP5 homologs efficiently quench PBS fluorescence in vitro, surpassing the quenching ability of the OCP. This is consistent with computational quantum mechanics/molecular mechanics results. Interestingly, when using a maximum quenching concentration of OCP with phycobilisomes, HCP5 addition further increases phycobilisome quenching. Our results provide mechanistic insight into the quenching capacity and roles of HCP4 and HCP5 in cyanobacteria, suggesting that they are more than simply functionally redundant to the OCP.

Mechanistic insights into allodynia in diabetic peripheral neuropathy.

Mechanistic insights into allodynia in diabetic peripheral neuropathy.

Enhanced emulsification properties of microalgae protein through gellan gum conjugation: Mechanistic insights and applications in curcumin encapsulation and delivery

The emulsification properties of microalgae protein (MP) are poor, especially under acidic and neutral conditions, which may limit the broad applications of MP in food processing. This study aims to explore the effects of gellan gum (GG) on the emulsification properties of MP. Firstly, MP-GG complexes were prepared and their structures characterized. Subsequently, MP-GG complexes stabilized emulsions were prepared and their stability evaluated. Finally, these emulsions were employed for the encapsulation and delivery of curcumin to evaluate their potential as an efficient nutrient delivery medium. Results indicated that MP-GG complexes were formed under various pH conditions, with pH 6 identified as optimal for complexes stability (zeta-potential value was −31 mV). UV–vis and fluorescence spectroscopy demonstrated that GG did not significantly alter the MP's structure but induced slight conformational changes, leading to the burial of some amino acid residues. Zeta potential measurements confirmed that MP-GG complexes were stabilized by strong electrostatic repulsions. The increase of GG content was conducive to providing more negative charge and promoting the dissolution and dispersion of the MP-GG complexes (MP: GG = 1: 1). Emulsions stabilized by MP-GG complexes exhibited smaller droplet sizes and improved stability compared to those stabilized by MP alone, especially at oil phase volume fractions of 60 % and 70 %. Rheological analysis indicated that GG enhanced emulsion stability by increasing viscosity, and higher oil phase volume fractions facilitated better MP-GG complexes adsorption on oil droplets, strengthening network structures of emulsions. During in vitro simulated gastrointestinal digestion, emulsions with a 70 % oil phase exhibited higher curcumin retention rate (31.09 %) and lower curcumin bioaccessibility (13.23 %) compared to those with a 60 % oil phase. This suggests that emulsions with higher oil phase volume fractions may be more suitable for colon-targeted curcumin delivery, with potential applications in promoting colon health. These findings confirm that the complexation of MP and GG was an effective way to improve the emulsification properties of MP. Emulsions stabilized by MP-GG complexes can serve as stable nutritional delivery systems for fat-soluble bioactive compounds.

Reduced microRNA-744 expression in mast cell-derived exosomes triggers epithelial cell ferroptosis in acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is a critical disorder characterized by immune-related damage to epithelial cells; however, its underlying mechanism remains elusive. This study investigated the effects of alterations in microRNA (miRNA) expression in mast cell-derived exosomes on human bronchial epithelial (HBE) cells and ARDS development in cellular and mouse models challenged with lipopolysaccharide. Lipopolysaccharide-treated mast cell-derived exosomes reduced glutathione peroxidase 4 (GPX4) expression and increased long-chain acyl-CoA synthetase 4 (ACSL4), 15-lipoxygenase (ALOX15), and inflammatory mediator levels in HBE cells. miRNA sequencing revealed a reduction in mast cell-derived exosomal miR-744 levels, which was associated with the regulation of ACSL4, ALOX15, and GPX4 expression. This downregulation of exosomal miR-744 expression reduced miR-744 levels and promoted ferroptosis in HBE cells, whereas the experimental upregulation of miR-744 reversed these adverse effects. Down-regulation of miR-744 induced the expression of markers for ferroptosis and inflammation in HBE cells and promoted pulmonary ferroptosis, inflammation, and injury in LPS-stimulated mice. In vivo, treatment with ACSL4, ALOX15, and GPX4 inhibitors mitigated these effects, and experimental miR-744 expression rescued the lipopolysaccharide-induced changes in HBE cells and mouse lungs. Notably, miR-744 levels were reduced in the plasma and exosomes of patients with ARDS. We concluded that decreased mast cell-derived exosomal miR-744 levels trigger epithelial cell ferroptosis, promoting lung inflammation and damage in ARDS. This study provides new mechanistic insights into the development and sustained pulmonary damage associated with ARDS and highlights potential therapeutic strategies.

Distinct contributions of microbial and plant residues to SOC during ecosystem primary succession in a Tibetan glacier foreland

Soil organic carbon (SOC) rapidly accumulates during ecosystem primary succession in glacier foreland. This makes it an ideal model for studying soil carbon sequestration and stabilization, which are urgently needed to mitigate climate change. Here, we investigated SOC dynamics in the Kuoqionggangri glacier foreland on the Tibetan Plateau. The study area along a deglaciation chronosequence of 170-year comprising three ecosystem succession stages, including barren ground, herb steppe, and legume steppe. We quantified amino sugars, lignin phenols, and relative expression of genes associated with carbon degradation to assess the contributions of microbial and plant residues to SOC, and used FT-ICR mass spectroscopy to analyze the composition of dissolved organic matter. We found that herbal plant colonization increased SOC by enhancing ecosystem gross primary productivity, while subsequent legumes development decreased SOC, due to increased ecosystem respiration from labile organic carbon inputs. Plant residues were a greater contributor to SOC than microbial residues in the vegetated soils, but they were susceptible to microbial degradation compared to the more persistent and continuously accumulating microbial residues. Our findings revealed the organic carbon accumulation and stabilization process in early soil development, which provides mechanism insights into carbon sequestration during ecosystem restoration under climate change.

Upgrading of nitrate to hydrazine through cascading electrocatalytic ammonia production with controllable N-N coupling.

Nitrogen oxides (NOx) play important roles in the nitrogen cycle system and serve as renewable nitrogen sources for the synthesis of value-added chemicals driven by clean electricity. However, it is challenging to achieve selective conversion of NOx to multi-nitrogen products (e.g., N2H4) via precise construction of a single N-N bond. Herein, we propose a strategy for NOx-to-N2H4 under ambient conditions, involving electrochemical NOx upgrading to NH3, followed by ketone-mediated NH3 to N2H4. It can achieve an impressive overall NOx-to-N2H4 selectivity of 88.7%. We elucidate mechanistic insights into the ketone-mediated N-N coupling process. Diphenyl ketone (DPK) emerges as an optimal mediator, facilitating controlled N-N coupling, owing to its steric and conjugation effects. The acetonitrile solvent stabilizes and activates key imine intermediates through hydrogen bonding. Experimental results reveal that Ph2CN* intermediates formed on WO3 catalysts acted as pivotal monomers to drive controlled N-N coupling with high selectivity, facilitated by lattice-oxygen-mediated dehydrogenation. Additionally, both WO3 catalysts and DPK mediators exhibit favorable reusability, offering promise for green N2H4 synthesis.

Translation of genome-wide association study: from genomic signals to biological insights

Since the turn of the 21st century, genome-wide association study (GWAS) have successfully identified genetic signals associated with a myriad of common complex traits and diseases. As we transition from establishing robust genetic associations with diverse phenotypes, the central challenge is now focused on characterizing the underlying functional mechanisms driving these signals. Previous GWAS efforts have revealed multiple variants, each conferring relatively subtle susceptibility, collectively contributing to the pathogenesis of various common diseases. Such variants can further exhibit associations with multiple other traits and differ across ancestries, plus disentangling causal variants from non-causal due to linkage disequilibrium complexities can lead to challenges in drawing direct biological conclusions. Combined with cellular context considerations, such challenges can reduce the capacity to definitively elucidate the biological significance of GWAS signals, limiting the potential to define mechanistic insights. This review will detail current and anticipated approaches for functional interpretation of GWAS signals, both in terms of characterizing the underlying causal variants and the corresponding effector genes.

Active Sites for CO2 Hydrogenation to Methanol: Mechanistic Insights and Reaction Control.

Catalytic CO2 conversion to methanol is a promising way to extenuate the adverse effects of CO2 emission, global warming and energy shortage. Understanding the fundamental features of CO2 activation and hydrogenation at the molecular level is essential for carbon utilization and sustainable chemical production in the current climate crisis. This review explores the recent advances in understanding the design of catalysts with desired active sites, including single-atom, dual-atom, interface, defects/vacancies and promoters/dopants. We focused on the design of various catalytic systems to enhance their catalytic performances by stabilizing active metal in a catalyst, identifying the unique structure of active species, and engineering coordination environments of active sites. Mechanistic insights provided by advanced operando and in situ spectroscopies were also discussed. Moreover, the review highlights the key factors affecting active sites and reaction mechanisms, such as local environments, oxidation states, and metal-support interactions. By integrating recent advancements and relating knowledge gaps this review aims to endow an inclusive overview of the field and guide future research toward more efficient and selective catalysts for CO2 hydrogenation to methanol.

Enhancing Aniline Condensation Reaction Efficiency Using Alkali and Rare Earth Element Modified USY Zeolite Catalyst: Synergistic Effects and Mechanistic Insights

Enhancing Aniline Condensation Reaction Efficiency Using Alkali and Rare Earth Element Modified USY Zeolite Catalyst: Synergistic Effects and Mechanistic Insights