Experimental Research Articles

Evolutionary Analysis of the hnRNP Interactomes and Their Functions in Eukaryotes.

The heterogeneous nuclear ribonucleoproteins (hnRNPs) are central regulators of several fundamental biological processes across eukaryotes. hnRNPs have been implicated in transcriptional and post-transcriptional regulation, telomere maintenance, stem cell maintenance, among other processes in major model organisms. Though hnRNPs are known to be conserved in eukaryotes, the evolutionary conservation/diversification of their functions across species is yet to be understood. To this end, the present work employed computational analyses to identify potential hnRNP orthologs in eighty eukaryotic species, and their interactors. Subsequently, a comprehensive analysis of the biological processes influenced by hnRNP interactomes showed alternative splicing and splicing regulation to be commonly associated with most species, while a few processes were uniquely associated with particular species. Further studies of the clustering patterns of the top-ranking hub nodes of the hnRNP protein networks revealed a notable clustering pattern of hnRNP K orthologs from five species. Subsequent analysis of the genes with overrepresented hnRNP K target sites within their untranslated regions showed hnRNP K orthologs from humans and Ciona intestanilis to potentially target transcripts involved in membrane-related processes. Remarkably, the hnRNP K ortholog from Lottia gigantea was found to possibly regulate other RNA-binding proteins (RBPs), suggesting a regulatory cascade involving hnRNPs and other RBPs. Further experimental studies in this regard would be of scientific and clinical importance, owing to the druggability of several human hnRNPs.

Visseral Lipectomy Improves Metabolic Syndrome Parameters and Adipokines in a Rat Model of Metabolic Syndrome Induced by Monosodium Glutamate.

Metabolic syndrome (MetS) includes abdominal obesity, hypertension, insulin resistance, and dyslipidemia. Research has indicated that reducing excess visceral fat has positive effects on inflammation and insulin resistance. We examined whether visceral lipectomy modifies the effects of MetS parameters and adipocytokine levels. Each group included 15 newborn male rats: control+sham (C+S), metabolic syndrome+sham (MetS+S), and metabolic syndrome+visceral lipectomy (MetS+VL). On postnatal days 0, 2, 4, 6, 8, and 10, subcutaneous injections of monosodium glutamate (MSG) (4g/mg) were administered to induce MetS. The control group received saline injection. The rats underwent sham surgery or lipectomy on the 120th day of life. Two months post-surgery, tests were performed to check lipid and insulin levels as well as the Lee index, HOMA-IR, serum adiponectin (ADP), resistin, interleukin-6 (IL6), leptin, tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP) levels. These findings showed that the Lee index (p = 0.001), insulin resistance (p = 0.002), and hyperinsulinemia (p = 0.009) were significantly improved in the MetS+VL group compared to those in the MetS+S group. The lipid profile was unaffected by visceral lipectomy. Furthermore, visceral lipectomy normalized MetS-induced adipokine imbalance. The decrease in the Lee index and improvement in hyperinsulinemia suggest that visceral lipectomy may benefit impaired glucose metabolism. Although visceral lipectomy has no apparent effect on the lipid profile, positive effects on adipokine levels by reducing various inflammatory markers including resistin, IL6, leptin, TNF-α, and CRP. These findings indicate that visceral lipectomy may have therapeutic potential for MetS. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Determining optimal pretreatment in cardiac surgery: an experimental study.

Heart failure patients with reduced ejection fraction are currently treated with four drug combinations: angiotensin receptor/neprilysin inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 inhibitors, resulting in improved survival outcomes. Herein, we examined whether myocardial protection by esaxerenone or sacubitril/valsartan may present a counter-effect to the harm caused by cardioplegic arrest. Male Wistar rats fed a normal diet were orally administered esaxerenone (3mg/kg; Esax) or sacubitril/valsartan (68mg/kg; SaV) once a day for 2weeks from 6weeks of age. Age-matched, untreated male Wistar rats served as controls (Control). Isolated rat hearts were aerobically Langendorff-perfused and subjected to 2min of St Thomas' Hospital 2 cardioplegia (STH2) infusion and 28min of normothermic global ischemia followed by 60min of reperfusion. The recovery of function was measured during 60min of reperfusion. Additionally, troponin T levels were measured after reperfusion as myocardial injury. The final recovery of left ventricular developed pressure (presented as the percentage of preischemic value) in the Control, Esax, and SaV groups was 50.7 ± 6.2%, 68.5 ± 7.4%*, and 69.3 ± 14.3%*, respectively (*p < 0.05 vs. Control). Troponin T (ng per gram wet weight) levels in the Control, Esax, and SaV groups were 166.8 ± 78.1, 77.0 ± 14.6*, and 74.2 ± 36.6*, respectively (*p < 0.05 vs. Control). Oral administration of esaxerenone or sacubitril/valsartan to rats 2weeks prior to surgery enhanced the myocardial protection afforded by STH2 and may attenuate the myocardial injury caused by hyperkalemic cardioplegic arrest.

Theoretical and experimental study on the polarization-independent flanged nanowire array infrared absorber.

An infrared (IR) absorber is a crucial component for thermal detectors, requiring high absorptance over a broad wavelength range while maintaining low heat capacity for optimal performance. Most thermal detectors use a thin film IR absorber that is suspended in air, supported by a layer beneath it for mechanical stability. However, this support layer increases heat capacity without contributing to IR absorptance, thereby reducing the performance of thermal detectors. In this paper, we introduce a polarization-independent nanowire array absorber using flanged nanowires with a C-shaped cross-section. This C-shaped design provides mechanical stability, eliminating the need for a support layer. Although nanowire array is generally known to exhibit polarization characteristics, the unique structure of the proposed flanged nanowires enables them to achieve polarization-independent properties, resulting in high absorptance similar to that of film absorbers. We theoretically analyzed the polarization-independent characteristics of the flanged nanowires using an optical circuit model and optimized the flanged nanowire structure using finite-difference time-domain (FDTD) simulations. Finally, we experimentally demonstrated the polarization-independent characteristics of the flanged nanowires and confirmed their high absorptance comparable to that of film absorbers.

Machining Characteristics During Short Hole Drilling of Titanium Alloy Ti10V2Fe3Al

The single-phase titanium ß-alloy Ti10V2Fe3Al (Ti-1023) has been widely used in the aerospace industry due to its unique mechanical properties, which include high fatigue strength and fracture toughness, as well as high corrosion resistance. On the other hand, these unique properties significantly hinder the cutting processes of this material, especially those characterized by a closed machining process area, such as drilling. This paper is devoted to the study of the short hole drilling process of the above-mentioned titanium alloy using direct measurements and numerical modeling. Measurements of the cutting force components in the drilling process and determination of the resultant cutting force and total cutting power were performed. The macro- and microstructure of chips generated during drilling were analyzed, and the dependence of the chip compression ratio and the distance between neighboring segments of serrated chips on cutting speed and drill feed was determined. Experimental studies were supplemented by determining the temperature on the lateral clearance face of the drill’s outer cutting insert in dependence on the cutting modes. For the modeling of the drilling process using the finite element model, the parameters of the triad of component submodels of the numerical model were determined: the machined material model, the model of contact interaction between the tool and the machined material, and the fracture model of the machined material. The determination of these parameters was performed through the DOE sensitivity analysis. The target values for performing this analysis were the total cutting power and the distance between neighboring chip segments. The maximum deviation between the simulated and experimentally determined values of the resulting cutting force is no more than 25%. At the same time, the maximum deviation between the measured values of the temperature on the lateral clearance face of the drill’s outer cutting insert and the corresponding simulated values is 26.1%.

Effect of sintering temperature on color stability and translucency of various zirconia systems after immersion in coffee solution.

Achieving the aesthetic standards in tooth-colored restorative materials requires close attention to their color, translucency, and resistance to discoloration. This study aimed to evaluate the effect of sintering temperature on color stability and translucency in zirconia systems with low, high, and ultra-high translucencies. This experimental study was conducted on 60 zirconia disks with low, high and ultra-high translucencies (n = 20 per group), each group divided into subgroups to be sintered at either 1450°C or 1550°C (n = 10 per subgroup). Baseline color and translucency parameters were measured, the specimens were then immersed in coffee solution for 30 days, and the measurements were repeated post-immersion. Changes in color (ΔE) and translucency (ΔTP) were calculated via CIELAB formula and compared by using two-way ANOVA and Tukey's post hoc test (α = 0.05). Results of two-way ANOVA showed that the ΔE was significantly different among the three zirconia translucencies (P<0.001), but no significant difference was found between the two sintering temperatures (P = 0.712). Additionally, the interaction between zirconia type and sintering temperature was not statistically significant for ΔE (P = 0.264). The low-translucency group showed significantly greater ΔE than the high-translucency and ultra-high-translucency groups (P<0.05), while the high- and ultra-high-translucency groups were not significantly different in this regard (P>0.05). Regarding the ΔTP, two-way ANOVA showed that the difference was not statistically significant either among the three zirconia types (P = 0.4430) or between the two sintering temperatures (P = 0.4544). Nor was the interaction between zirconia type and sintering temperature statistically significant (P = 0.5505). It was concluded that sintering temperature had no effect on color and translucency changes after immersion in coffee. Whereas zirconia type significantly affected the color changes after immersion in coffee; with the higher-translucency zirconia types being significantly more color-stable than the low-translucency zirconia.

Meta-analysis of a Moderate-to-Vigorous Physical Activity Intervention for Academic Achievement in Children and Adolescents.

To analyze the intervention effect of moderate-to-vigorous physical activity (MVPA) on the academic performance of children and adolescents. Experimental studies on the effects of MVPA on the academic performance of children and adolescents were comprehensively searched in Web of Science, China Knowledge Network and other databases, and the Cochrane Risk of Bias Assessment Tool was used to assess the quality of the literature, and the Meta-analysis was performed by Review Manager 5.3. 1) A total of 11 high-quality literature were included, including 4552 subjects; 2) MVPA had a positive effect on the academic performance of children and adolescents (SMD=0.24; 95%CI:0.13, 0.35, P<0.0001), with differences in the effect of different subjects, and the mathematics has the best effect (SMD=0.23; 95%CI:0.11, 0.34, P≤0.0001), followed by reading (SMD=0.24; 95% CI:0.02, 0.46, P<0.05), and the comprehensive achievement intervention effect was not significant (SMD=0.33; 95% CI:-0.15, 0.80, P=0.18); 3) MVPA has the greatest impact on children aged 9-11 years (SMD=0.30; 95%CI:0.06, 0.54, P<0.05); 4) The optimal dose of intervention for MVPA is a long cycle of 30-60 minutes per session(SMD=0.34; 95%CI:0.12, 0.56, P<0.01), 2 times per week(SMD=0.28; 95%CI:0.2, 0.35, P<0.001); 5) The effect of literature publication bias detection was positive. 1) MVPA has a moderate effect on promoting academic achievement in children and adolescents, with younger age groups often benefiting more than older adolescents due to age-related cognitive plasticity; 2) MVPA has limited intervention effect on the performance of other subjects, which leads to the unsatisfactory effect of the intervention on the comprehensive performance; 3) Attention should be paid to the fine control of the intensity of the physical activity to guarantee individual MVPA participation to promote the academic achievement of children and adolescents; 4) Long-term participation, 30-60 minutes per session, 2-3 times per week of MVPA has been shown to be an effective intervention dose to enhance academic performance.

Performance, combustion and emission parameters of Scenedesmus obliquus methyl ester in single-cylinder CI engine: an experimental study

Performance, combustion and emission parameters of Scenedesmus obliquus methyl ester in single-cylinder CI engine: an experimental study

Citrate in autosomal dominant polycystic kidney disease: biomarker or therapeutic agent?

Purpose of review This review highlights the latest findings regarding hypocitraturia in autosomal dominant polycystic kidney disease (ADPKD), from both experimental and clinical studies, exploring the underlying pathophysiology and potential therapeutic approach. Recent findings Experimental studies have shown that the lodging of microcrystals in the tubules can trigger cyst formation and growth in polycystic kidney disease (PKD). ADPKD patients are prone to developing hypocitraturia in early stages, which could predispose to calcium microcrystal formation. Low urinary citrate excretion has been associated with a more rapid decline in eGFR and poorer renal survival in ADPKD patients. Animal studies employing citrate supplementation have shown promising effects on preserving the decline in estimated glomerular filtration rate (eGFR) and cyst growth. Summary Current knowledge suggests that urinary citrate could be incorporated into existing prognostic markers for disease progression and potential adjuvant therapy in ADPKD, but further clinical studies to support such hypothesis must be undertaken.

Pupil size and iris brightness interact to affect prosocial behaviour and affective responses

ABSTRACT Despite the tight link between the visibility of the iris and pupil, the perceived effects of these two have been studied largely in isolation. We demonstrate, across two experimental studies, that the effects of perceived pupil size are dependent on the visibility of the iris. In a first study, our participants donated more and had more positive impressions of portraits of non-human primates when these were manipulated to appear having larger pupils. Post-hoc inspection of our data suggested that the difference was greater for species with more conspicuous irises. In a second study, we concomitantly manipulated iris brightness and pupil size. Brighter irises and larger pupils elicited greater donations. Participants rated photographs with brighter irises as cuter, more attractive and friendlier, but only when they had dilated pupils. Our results have methodological implications for studies manipulating eye appearance, and help interpret results from previous studies.

Abstract A019: Identification and Genomic Analysis of miRNA-mRNA Binding Site SNPs in Hepatitis C Virus-Associated Hepatocellular Carcinoma

Abstract Hepatitis C virus (HCV) infection is a major risk factor for hepatocellular carcinoma (HCC), a leading cause of cancer-related deaths globally. MicroRNAs (miRNAs) play critical roles in gene regulation, and single nucleotide polymorphisms (SNPs) within miRNA binding sites can disrupt this regulation, potentially influencing HCC pathogenesis. The present study aims to identify and characterize SNPs within miRNA binding sites of genes associated with HCV- induced HCC (HCV-HCC). A comprehensive bioinformatics analysis workflow was devised. HCV-specific differentially expressed (DE) miRNAs and mRNAs were extracted from literature and databases. SNPs in the 3' UTRs of HCV-HCC genes were identified, and their impact on miRNA binding was predicted using PoymiRTS and TargetScan. RNAhybrid was used to estimate minimum folding energy (MFE) differences (ΔMFE) between mutant and wild types. Functional enrichment analysis was conducted to elucidate the biological processes affected by these SNPs. Our analysis revealed several significant alterations in miRNA-mRNA binding pairs due to SNPs within genes associated with HCV-HCC. For instance, among the downregulated genes in HCV-HCC, the SNP in CTSB (rs3088245; 193T&amp;gt;C) predicted to increase the stability of the miR-27b - CTSB duplex (ΔMFE: 1.4), suggesting enhanced binding and potentially improved repression of CTSB. Conversely, the SNP in EGR2 (rs61865883; 287 T&amp;gt;A) decreased the stability of the miR-140-5p - EGR2 mRNA interaction (ΔMFE: -1.9), suggesting a weaker binding affinity and potentially reduced repression of EGR2 expression. Considering the tumor suppressor role of EGR2, presence of this SNP is likely to reflect good prognosis. For the upregulated gene oncogene, XIAP, the SNP (rs6648556; 5892 T&amp;gt;C) is predicted to enhance the binding of miR- 200c (ΔMFE: 1.5), likely resulting in increased suppression of XIAP expression in patients carrying this SNP and improved prognosis. Our study emphasizes the importance of considering genetic variations in miRNA binding sites in the context of HCV-HCC. These SNPs may serve as genetic modifiers influencing disease susceptibility and progression. Further experimental studies are warranted to explore their potential as therapeutic agents and predictors of prognosis in HCV-HCC patients. Citation Format: Azeem M Butt, Anum Qamar, Shafiqa Siddique. Identification and Genomic Analysis of miRNA-mRNA Binding Site SNPs in Hepatitis C Virus-Associated Hepatocellular Carcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr A019.

Gender variability in palpation performance for temporomandibular disorders with three different methods: An experimental study.

Gender differences in pain reporting and prevalence have been demonstrated. As gender of examiner also affects reporting of pain on palpation, the aim of this study was to evaluate the effects of examiner gender on palpation performance using three different palpation methods. Examiners of both genders were instructed on the correct technique for each palpation method by either a female or male instructor. The target was to achieve a pressure of 100kPa, corresponding tothe 1kg of force for muscle palpation described in the diagnostic criteria for temporomandibular disorders (DC/TMD). All examiners performed traditional palpation with the index finger, palpation with a palpometer, and a novel bimanual palpation with visual feedback, in a randomized order. The examiner's gender, and its interaction with the gender of the instructor did not significantly affect magnitude, accuracy, or precision of the pressure applied. The method of palpation was the only factor that significantly impacted all metrics. The palpometer achieved the lowest palpation magnitude (mean pressure applied=113.7kPa, 95% CI: 109.8-117.6), the highest accuracy (absolute difference=15.7kPa, 95% CI: 12.3-19.1), and the highest precision (mean coefficient of variation=6.8, 95% CI: 6.0-7.6), followed by bimanual palpation and traditional palpation. The results suggest that gender differences in pain reporting in patients are not likely to be a result of the technical aspects associated with the gender of the examiner. Instead, these differences may be attributed to other factors, such as sociocultural influences.

Remarkably Boosted High‐Temperature Electrostatic Energy Storage of Polyetherimide Film Induced by TiO2@Au@AlOx@Au Core‐shell Nanofibers

AbstractPolymer dielectrics have broad applications in advanced electronics and power systems. However, they suffer from low energy density and poor breakdown performance at high temperatures, limiting their applications in high‐temperature environments. Herein, TiO2@Au@AlOx@Au nanofibers with double coulomb blockade nanolayers are obtained via a physical sputtering strategy to improve the high‐temperature energy storage performance of polyetherimide composites. Experimental studies and finite elemenet phase‐field simulations demonstrate that the double‐layer coulomb blockade effect and micro‐capacitor effect of Au nanoparticles synergistically enhance the breakdown strength and dielectric permittivity of polyetherimide composite at high temperatures. Notably, the composite exhibits ultra‐high discharged energy densities of 11.33 and 9.70 J cm−3 at 150 and 200 °C, respectively, along with high charge–discharge efficiencies of 93.4% and 84%, which far exceed that of the polymer nanocomposites reported so far. Furthermore, the composite exhibits excellent charge–discharge cycling performance (&gt;50000 cycles at 400 MV m−1) and high‐power density (1.16 MW cm−3) at 200 °C, making it an ideal candidate for high‐temperature capacitors. Hopefully, these nanofibers not only serve as excellent nanofillers for high‐temperature energy storage dielectric composites but also holds tremendous potential and inspirational significance for other applications such as electronics, biomedical fields, optics, and catalysis.

Unraveling the Synergistic Role of Kinks in Zig-Zag Ag2Se Nanorod Arrays for High Room-Temperature zT and Improved Mechanical Properties: Experimental and First-Principles Studies.

Flexible thermoelectric materials are usually fabricated by incorporating conducting or organic polymers; however, it remains a formidable task to achieve high thermoelectric properties comparable to those of their inorganic counterparts. Here, we present a high zT value of 1.29 ± 0.31 at room temperature in the hierarchical zig-zag Ag2Se nanorod arrays fabricated using the glancing angle deposition (GLAD) technique followed by a facile selenization process. The high zT value at 300 K is ascribed to the ultrahigh power factor of 3101 ± 252 μW/m-K2 and the reduced thermal conductivity of 0.72 ± 0.01 W/mK. Based on ab initio computational and experimental evidence, we reveal that kinked Ag2Se nanorod arrays consisting of rough interfaces modulate the lattice thermal conductivity up to 48.5% at room temperature. The modulation results from interchanging of phonon modes at kink points and enhanced scattering from a large number of rough interfaces. Further, benefiting from kinked hierarchy, a notable improvement in the mechanical performance is observed for zig-zag Ag2Se nanorods which is confirmed by nanoindentation measurements. The synergic improvement in thermoelectric and mechanical performance not only unravels a paradigm to harness thermoelectric heat but also offers deeper insights into tuning the mechanical properties of inorganic thermoelectric materials.

‘Crushing The Stress’: An Experimental Study on the Positive Impact of Casual Video Games in Indian Context

Research on Casual Video Gaming in the Indian context are focused on exploring the negative ramifications of gameplay such as addiction and sedentary lifestyle effects. With the rise of video game interventions and increased use of casual games for cognitive training and stress relief in applied settings, there is a need to analyze the positive ramifications of casual video games in India. In this research study, two positive benefits of casual games are looked at: stress relief and cognitive benefits. The research is a repeated measures experimental design study that aims to examine these positive effects in contrast to an assigned control task. 30 participants, between the ages of 18-28 years act as their own controls. The study analyzes the impact of popular American casual game, Bejeweled Classic on stress; measured through blood pressure, heart-rate and state anxiety; and reaction time through the Stroop Task. The data was analyzed using a paired sample t-test. Results did not support the first hypothesis that casual video games reduce stress. The second benefit, however, that of cognitive benefits of casual games, was found to be statistically significant by a p value of 0.01. The study is useful in contributing to the literature of Indian studies that examine positive ramifications of casual games.

Serum uric acid is independently associated with impaired nitroglycerine-induced vasodilation of the brachial artery in women.

Experimental and clinical studies have suggested atherosclerotic effects of uric acid (UA) on vascular smooth muscle cells (VSMCs). Nitroglycerine-induced vasodilation (NID), a control test for flow-mediated vasodilation, can be used as a possible marker of VSMC dysfunction. However, there is little information on the association between UA and NID. Therefore, we investigated the association between serum UA levels and NID according to sex. We measured NID of the brachial artery in 598 women (mean age: 66.2 ± 12.0 years) and 1008 men (mean age: 59.0 ± 18.0 years). In women, the mean serum UA level was 5.06 ± 1.24 mg/dL. Serum UA levels were negatively correlated with NID (p < 0.001), and NID significantly decreased with increasing serum UA levels (≤4.0 mg/dL, 13.4 ±6.4%; 4.0 to ≤5.0 mg/dL, 11.4 ± 5.3%; 5.0 to ≤6.0 mg/dL, 10.8 ± 5.7%; >6.0 mg/dL, 9.7 ± 5.7%; p < 0.001). The prevalence of VSMC dysfunction, defined as NID < 8.4%, the division points for the lowest and middle tertiles of NID in women, increased with increasing serum UA levels ( ≤ 4.0 mg/dL, 23.3%; 4.0 to ≤5.0 mg/dL, 30.9%; 5.0 to ≤6.0 mg/dL, 36.4%; >6.0 mg/dL, 44.6%; p < 0.001). Multiple logistic regression analysis showed a significant association between serum UA levels and VSMC dysfunction (odds ratio, 1.21; 95% confidence interval, 1.02─1.43; p = 0.03). There was no interaction between age (<50 or ≥50 years) and the effect of serum UA levels on VSMC dysfunction (p interaction = 0.88). In contrast, no association was observed between serum UA levels and NID in men. Serum UA levels were significantly associated with VSMC dysfunction as assessed by NID in women.

Novel perspectives on the link between obesity and cancer risk: from mechanisms to clinical implications.

Existing epidemiologic and clinical studies have demonstrated that obesity is associated with the risk of a variety of cancers. In recent years, an increasing number of experimental and clinical studies have unraveled the complex relationship between obesity and cancer risk and the underlying mechanisms. Obesity-induced abnormalities in immunity and biochemical metabolism, including chronic inflammation, hormonal disorders, dysregulation of adipokines, and microbial dysbiosis, may be important contributors to cancer development and progression. These contributors play different roles in cancer development and progression at different sites. Lifestyle changes, weight loss medications, and bariatric surgery are key approaches for weight-centered, obesity-related cancer prevention. Treatment of obesity-related inflammation and hormonal or metabolic dysregulation with medications has also shown promise in preventing obesity-related cancers. In this review, we summarize the mechanisms through which obesity affects the risk of cancer at different sites and explore intervention strategies for the prevention of obesity-associated cancers, concluding with unresolved questions and future directions regarding the link between obesity and cancer. The aim is to provide valuable theoretical foundations and insights for the in-depth exploration of the complex relationship between obesity and cancer risk and its clinical applications.

Nile Red Fluorescence: Where's the Twist?

Nile Red is a fluorescent dye used extensively in bioimaging due to its strong solvatochromism. The photophysics underpinning Nile Red's fluorescence has been disputed for decades, with some studies claiming that the dye fluoresces from two excited states and/or that the main emissive state is twisted and intramolecular charge-transfer (ICT) in character as opposed to planar ICT (PICT). To resolve these long-standing questions, a combined experimental and theoretical study was used to unravel the mechanism of Nile Red's fluorescence. Time-resolved fluorescence measurements indicated that Nile Red emission occurs from a single excited state. Theoretical calculations revealed no evidence for a low-lying TICT state, with the S1 minimum corresponding to a PICT state. Ultrafast pump-probe spectroscopic data contained no signatures associated with an additional excited state involved in the fluorescence decay of Nile Red. Collectively, these data in polar and nonpolar solvents refute dual fluorescence in Nile Red and definitively demonstrate that emission occurs from a PICT state.

Low-Spin Fe3+ Evoked by Multiple Defects with Optimal Intermediate Adsorption Attaining Unparalleled Performance in Water Oxidation.

Electrocatalytic water splitting is long constrained by the sluggish kinetics of anodic oxygen evolution reaction (OER), and rational spin-state manipulation holds great promise to break through this bottleneck. Low-spin Fe3+ (LS, t2g 5eg 0) species are identified as highly active sites for OER in theory, whereas it is still a formidable challenge to construct experimentally. Herein, a new strategy is demonstrated for the effective construction of LS Fe3+ in NiFe-layered double hydroxide (NiFe-LDH) by introducing multiple defects, which induce coordination unsaturation over Fe sites and thus enlarge their d orbital splitting energy. The as-obtained catalyst exhibits extraordinary OER performance with an ultra-low overpotential of 244 mV at the industrially required current density of 500 mA cm-2, which is 110 mV lower than that of the conventional NiFe-LDH with high-spin Fe3+ (HS, t2g 3eg 2) and superior to most previously reported NiFe-based catalysts. Comprehensive experimental and theoretical studies reveal that LS Fe3+ configuration effectively reduces the adsorption strength of the O* intermediate compared with that of the HS case, thereby altering the rate-determining step from (O* → OOH*) to (OH* → O*) of OER and lowering its reaction energy barrier. This work paves a new avenue for developing efficient spin-dependent electrocatalysts for OER and beyond.

Brain-wide alterations revealed by spatial transcriptomics and proteomics in COVID-19 infection.

Understanding the pathophysiology of neurological symptoms observed after severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection is essential to optimizing outcomes and therapeutics. To date, small sample sizes and narrow molecular profiling have limited the generalizability of findings. In this study, we profiled multiple cortical and subcortical regions in postmortem brains of patients with coronavirus disease 2019 (COVID-19) and controls with matched pulmonary pathology (total n = 42) using spatial transcriptomics, bulk gene expression and proteomics. We observed a multi-regional antiviral response without direct active SARS-CoV2 infection. We identified dysregulation of mitochondrial and synaptic pathways in deep-layer excitatory neurons and upregulation of neuroinflammation in glia, consistent across both mRNA and protein. Remarkably, these alterations overlapped substantially with changes in age-related neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. Our work, combining multiple experimental and analytical methods, demonstrates the brain-wide impact of severe acute/subacute COVID-19, involving both cortical and subcortical regions, shedding light on potential therapeutic targets within pathways typically associated with pathological aging and neurodegeneration.