A High Visceral to Skeletal Muscle Area Ratio on Cross sectional Imaging is Associated with Failure of Standard Ustekinumab Doses, a Multicentre study.

BACKGROUND: Anti-IL12/23 agents have shown greater durability in response compared with anti-TNFα agents. Data on the association between body composition or body mass index (BMI) and Ustekinumab's (Ust) therapeutic response is limited. We aimed to evaluate the impact of body composition on time to failing standard doses of Ust in Crohn's disease (CD) patients. METHOD: Adult CD patients aged ≥16 yrs. from two tertiary centres were studied retrospectively. Included patients had abdominal imaging within 6 months of Ust induction and were followed up until 30th April 2022. An experienced abdominal radiologist blinded to the clinical information measured the area of visceral fat (VFA), skeletal muscle area (SMA) at the mid L3 vertebral level, with values corrected for height2 to derive respective indices (VFI, SMI) and the VFI:SMI ratio. RESULTS: 99 patients met inclusion criteria. The mean age at Ust induction was 46.6 (±1.6) years. The median BMI (IQR) was 26.5 (22.6, 30.8). 24 patients (24.2%) did not respond or lost response to standard doses of Ust over the follow up duration. A younger age ((HR: 0.96, 95%CI: 0.94-0.99, P=0.01) and a VFI:SMI ratio >1.6 (HR: 4.65, 95%CI: 1.73-12.45, P= 0.002), were both associated with a shorter time failing Ust at standard doses on multivariate analysis. BMI notably, had no association with the primary outcome. CONCLUSION: A high VFI: SMI ratio is associated with an increased risk of failing standard doses of Ust. Body composition measurements derived from cross sectional imaging at the start of Ust therapy is a useful indicator for therapeutic durability.

Identification and validation of potential diagnostic signature and immune cell infiltration for HIRI based on cuproptosis-related genes through bioinformatics analysis and machine learning.

Background and aims: Cuproptosis has emerged as a significant contributor in the progression of various diseases. This study aimed to assess the potential impact of cuproptosis-related genes (CRGs) on the development of hepatic ischemia and reperfusion injury (HIRI). Methods: The datasets related to HIRI were sourced from the Gene Expression Omnibus database. The comparative analysis of differential gene expression involving CRGs was performed between HIRI and normal liver samples. Correlation analysis, function enrichment analyses, and protein-protein interactions were employed to understand the interactions and roles of these genes. Machine learning techniques were used to identify hub genes. Additionally, differences in immune cell infiltration between HIRI patients and controls were analyzed. Quantitative real-time PCR and western blotting were used to verify the expression of the hub genes. Results: Seventy-five HIRI and 80 control samples from three databases were included in the bioinformatics analysis. Three hub CRGs (NLRP3, ATP7B and NFE2L2) were identified using three machine learning models. Diagnostic accuracy was assessed using a receiver operating characteristic (ROC) curve for the hub genes, which yielded an area under the ROC curve (AUC) of 0.832. Remarkably, in the validation datasets GSE15480 and GSE228782, the three hub genes had AUC reached 0.904. Additional analyses, including nomograms, decision curves, and calibration curves, supported their predictive power for diagnosis. Enrichment analyses indicated the involvement of these genes in multiple pathways associated with HIRI progression. Comparative assessments using CIBERSORT and gene set enrichment analysis suggested elevated expression of these hub genes in activated dendritic cells, neutrophils, activated CD4 memory T cells, and activated mast cells in HIRI samples versus controls. A ceRNA network underscored a complex regulatory interplay among genes. The genes mRNA and protein levels were also verified in HIRI-affected mouse liver tissues. Conclusion: Our findings have provided a comprehensive understanding of the association between cuproptosis and HIRI, establishing a promising diagnostic pattern and identifying latent therapeutic targets for HIRI treatment. Additionally, our study offers novel insights to delve deeper into the underlying mechanisms of HIRI.

Identification of a pathogenic SMCHD1 variant in a Chinese patient with bosma arhinia microphthalmia syndrome: a case report.

BACKGROUND: Bosma arhinia microphthalmia syndrome (BAMS; MIM603457) is a rare genetic disorder, predominantly autosomal dominant. It is a multi-system developmental disorder characterized by severe hypoplasia of the nose and eyes, and reproductive system defects. BAMS is extremely rare in the world and no cases have been reported in Chinese population so far. Pathogenic variants in the SMCHD1 gene (MIM614982) cause BAMS, while the underlying molecular mechanisms requires further investigation. CASE PRESENTATION: In this study, a Chinese girl who has suffered from congenital absence of nose and microphthalmia was enrolled and subsequently submitted to a comprehensive clinical and genetic evaluation. Whole-exome sequencing (WES) was employed to identify the genetic entity of thisgirl. A heterozygous pathogenic variant, NM_015295, c.1025G > C; p. (Trp342Ser) of SMCHD1 was identified. By performing very detailed physical and genetic examinations, the patient was diagnosed as BAMS. CONCLUSION: This report is the first description of a variant in SMCHD1 in a Chinese patient affected with BAMS.Our study not only furnished valuable genetic data for counseling of BAMS, but also confirmed the diagnosis of BAMS, which may help the management and prognosis for this patient.

Identification of potent pan-ephrin receptor kinase inhibitors using DNA-encoded chemistry technology.

EPH receptors (EPHs), the largest family of tyrosine kinases, phosphorylate downstream substrates upon binding of ephrin cell surface-associated ligands. In a large cohort of endometriotic lesions from individuals with endometriosis, we found that EPHA2 and EPHA4 expressions are increased in endometriotic lesions relative to normal eutopic endometrium. Because signaling through EPHs is associated with increased cell migration and invasion, we hypothesized that chemical inhibition of EPHA2/4 could have therapeutic value. We screened DNA-encoded chemical libraries (DECL) to rapidly identify EPHA2/4 kinase inhibitors. Hit compound, CDD-2693, exhibited picomolar/nanomolar kinase activity against EPHA2 (Ki: 4.0 nM) and EPHA4 (Ki: 0.81 nM). Kinome profiling revealed that CDD-2693 bound to most EPH family and SRC family kinases. Using NanoBRET target engagement assays, CDD-2693 had nanomolar activity versus EPHA2 (IC50: 461 nM) and EPHA4 (IC50: 40 nM) but was a micromolar inhibitor of SRC, YES, and FGR. Chemical optimization produced CDD-3167, having picomolar biochemical activity toward EPHA2 (Ki: 0.13 nM) and EPHA4 (Ki: 0.38 nM) with excellent cell-based potency EPHA2 (IC50: 8.0 nM) and EPHA4 (IC50: 2.3 nM). Moreover, CDD-3167 maintained superior off-target cellular selectivity. In 12Z endometriotic epithelial cells, CDD-2693 and CDD-3167 significantly decreased EFNA5 (ligand) induced phosphorylation of EPHA2/4, decreased 12Z cell viability, and decreased IL-1ß-mediated expression of prostaglandin synthase 2 (PTGS2). CDD-2693 and CDD-3167 decreased expansion of primary endometrial epithelial organoids from patients with endometriosis and decreased Ewing's sarcoma viability. Thus, using DECL, we identified potent pan-EPH inhibitors that show specificity and activity in cellular models of endometriosis and cancer.

Visual Pathway Recovery Post Pituitary Adenoma Surgery: Insights from Retinal Structure, Vascular Density, and Neural Conduction Analysis.

INTRODUCTION: This study investigates how surgery for pituitary adenoma (PA) affects the visual pathway, examining changes in the retina, blood vessel density, and nerve function. Since PAs often impair vision as a result of their location near visual structures, this research is key to understanding and improving vision recovery after surgery. METHODS: Our study is based on a retrospective analysis of the historical data of 28 patients diagnosed with pituitary adenomas. We conducted assessments by reviewing preoperative and postoperative imaging records. These included optical coherence tomography (OCT) for retinal structure analysis, diffusion tensor imaging (DTI) for neural transmission evaluation, and optical coherence tomography angiography for assessing blood vessel density. These tools allowed for a detailed understanding of the structural and functional changes within the visual pathway following PA surgery. RESULTS: OCT findings show postoperative changes in the eye: thinning in average and nasal circumpapillary retinal nerve fiber layer, thickening in macular central 1 mm inner plexus layer, ganglion cell complex, and nasal retinal nerve fiber layer. DTI reveals increased fractional anisotropy (FA) in the left optic chiasm and posterior optic nerve, decreased mid-segment optic nerve FA, and increased apparent diffusion coefficient (ADC) in the right optic chiasm and nerve segments. Early postoperative reduction in radial peripapillary capillaries plexus density is noted. Preoperative ganglion cell layer (GCL) thickness correlates with postoperative visual radiation FA and ADC values, especially in the inferior quadrant. A negative correlation exists between preoperative GCL thickness and postoperative visual field mean defect values, particularly on the temporal side and superior inner ring. All changes are statistically significant (P < 0.05). CONCLUSIONS: The study finds that surgery for PA has varied effects on vision. Early post surgery, there are changes in the retina and nerve signals. Macular GCL thickness before surgery might predict early visual recovery, influencing future research and treatment for vision issues related to PA.

Flexible, biodegradable ultrasonic wireless electrotherapy device based on highly self-aligned piezoelectric biofilms.

Biodegradable piezoelectric devices hold great promise in on-demand transient bioelectronics. Existing piezoelectric biomaterials, however, remain obstacles to the development of such devices due to difficulties in large-scale crystal orientation alignment and weak piezoelectricity. Here, we present a strategy for the synthesis of optimally orientated, self-aligned piezoelectric γ-glycine/polyvinyl alcohol (γ-glycine/PVA) films via an ultrasound-assisted process, guided by density functional theory. The first-principles calculations reveal that the negative piezoelectric effect of γ-glycine originates from the stretching and compression of glycine molecules induced by hydrogen bonding interactions. The synthetic γ-glycine/PVA films exhibit a piezoelectricity of 10.4 picocoulombs per newton and an ultrahigh piezoelectric voltage coefficient of 324 × 10-3 volt meters per newton. The biofilms are further developed into flexible, bioresorbable, wireless piezo-ultrasound electrotherapy devices, which are demonstrated to shorten wound healing by ~40% and self-degrade in preclinical wound models. These encouraging results offer reliable approaches for engineering piezoelectric biofilms and developing transient bioelectronics.

Association Between Dietary Factors and Chronic Sinusitis Among Korean Individuals: Insights From a Large Population-Based Study in Asia.

Objective: Population-based studies on chronic sinusitis have predominantly focused on Europe and the Americas, but research on chronic sinusitis within large Asian populations remains scarce. This study aims to explore the link between dietary factors and chronic sinusitis among ethnic Koreans in Asia. Design: A cross-sectional study. Setting: Data were collected from the Korean National Health and Nutrition Examination Survey (KNHANES) in 2012. Participants: Participants in the study were included based on a doctor's diagnosis of chronic sinusitis, as determined through the ear, nose, and throat examination questionnaires. Results: Adolescents [adjusted P value (aP) < .001, adjusted odds ratio (aOR) = 1.881, 95% confidence interval (CI) = 1.380-2.564] and individuals with college and higher education (aP = .042, aOR = 1.298, 95% CI = 1.009-1.669) were more likely to develop chronic rhinosinusitis. In addition, levels of dietary fat [P = .001, interquartile range (IQR) = 34.085] and energy intake (P = .004, IQR = 981.106) were associated with an increased risk of chronic sinusitis. Moreover, high dietary inflammatory index (aP < .001, aOR = 0.547, 95% CI = 0.415-0.721), and high intake of fried pork chops (aP = .028, aOR = 1.335, 95% CI = 1.033-1.777), bread (aP = .024, aOR = 1.364, 95% CI = 1.042-1.786), and rice (aP = .021, aOR = 1.382, 95% CI = 1.051-1.818) were risk factors for chronic sinusitis, while cucumber consumption (aP < .001, aOR = 0.547, 95% CI = 0.415-0.721) was a protective factor for chronic sinusitis. Conclusion: This study revealed a significant correlation between diet and development of chronic sinusitis. These findings suggest that promoting an anti-inflammatory dietary pattern and providing guidance on healthy eating habits could help reduce the incidence of chronic sinusitis and enhance its management.

Reversible male contraception by targeted inhibition of serine/threonine kinase 33.

Men or mice with homozygous serine/threonine kinase 33 (STK33) mutations are sterile owing to defective sperm morphology and motility. To chemically evaluate STK33 for male contraception with STK33-specific inhibitors, we screened our multibillion-compound collection of DNA-encoded chemical libraries, uncovered potent STK33-specific inhibitors, determined the STK33 kinase domain structure bound with a truncated hit CDD-2211, and generated an optimized hit CDD-2807 that demonstrates nanomolar cellular potency (half-maximal inhibitory concentration = 9.2 nanomolar) and favorable metabolic stability. In mice, CDD-2807 exhibited no toxicity, efficiently crossed the blood-testis barrier, did not accumulate in brain, and induced a reversible contraceptive effect that phenocopied genetic STK33 perturbations without altering testis size. Thus, STK33 is a chemically validated, nonhormonal contraceptive target, and CDD-2807 is an effective tool compound.

Ultra-high piezoelectric properties and ultra-high Curie temperature of Li/Ce-doped La2Ti2O7 ceramics.

The demand for ultra-high-temperature piezoelectric sensors in industrial applications has witnessed a rapid upsurge. In this study, the piezoelectric properties of La2Ti2O7 (LTO) piezoelectric ceramics with a perovskite-like layered structure were enhanced by doping with Li/Ce ions. It was found that a remarkable 300% enhancement in the piezoelectric constant (d33) value was achieved in Li/Ce-doped LTO ceramics compared to their pristine counterparts, reaching 6.4 pC N-1 at room temperature with an ultra-high Curie temperature of 1408 °C. After annealing at 500 °C, the d33 value of the samples can be further improved to 7.4 pC N-1. Moreover, temperature-dependent resistivity measurements indicate that even at 1000 °C, the ceramics exhibit a high resistivity of 8.9 × 105 Ω cm. By combining X-ray diffraction, Raman spectra, transmission electron microscopy and piezoresponse force microscopy data, the enhanced piezoelectricity of the ceramics is attributed to local heterogeneity induced by Li/Ce doping. Our results unequivocally demonstrate the suitability of modified LTO ceramics for ultra-high-temperature piezoelectric applications.

Lymph node metastasis prediction and biological pathway associations underlying DCE-MRI deep learning radiomics in invasive breast cancer.

BACKGROUND: The relationship between the biological pathways related to deep learning radiomics (DLR) and lymph node metastasis (LNM) of breast cancer is still poorly understood. This study explored the value of DLR based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in LNM of invasive breast cancer. It also analyzed the biological significance of DLR phenotype based on genomics. METHODS: Two cohorts from the Cancer Imaging Archive project were used, one as the training cohort (TCGA-Breast, n = 88) and one as the validation cohort (Breast-MRI-NACT Pilot, n = 57). Radiomics and deep learning features were extracted from preoperative DCE-MRI. After dual selection by principal components analysis (PCA) and relief methods, radiomics and deep learning models for predicting LNM were constructed by the random forest (RF) method. A post-fusion strategy was used to construct the DLR nomograms (DLRNs) for predicting LNM. The performance of the models was evaluated using the receiver operating characteristic (ROC) curve and Delong test. In the training cohort, transcriptome data were downloaded from the UCSC Xena online database, and biological pathways related to the DLR phenotypes were identified. Finally, hub genes were identified to obtain DLR gene expression (RadDeepGene) scores. RESULTS: DLRNs were based on area under curve (AUC) evaluation (training cohort, AUC = 0.98; validation cohort, AUC = 0.87), which were higher than single radiomics models or GoogLeNet models. The Delong test (radiomics model, P = 0.04; GoogLeNet model, P = 0.01) also validated the above results in the training cohorts, but they were not statistically significant in the validation cohort. The GoogLeNet phenotypes were related to multiple classical tumor signaling pathways, characterizing the biological significance of immune response, signal transduction, and cell death. In all, 20 genes related to GoogLeNet phenotypes were identified, and the RadDeepGene score represented a high risk of LNM (odd ratio = 164.00, P < 0.001). CONCLUSIONS: DLRNs combining radiomics and deep learning features of DCE-MRI images improved the preoperative prediction of LNM in breast cancer, and the potential biological characteristics of DLRN were identified through genomics.

CYP3A Mediates an Unusual C(sp2)-C(sp3) Bond Cleavage via Ipso-Addition of Oxygen in Drug Metabolism.

Mammalian cytochrome P450 drug-metabolizing enzymes rarely cleave carbon-carbon (C-C) bonds and the mechanisms of such cleavages are largely unknown. We identified two unusual cleavages of non-polar, unstrained C(sp2)-C(sp3) bonds in the FDA-approved tyrosine kinase inhibitor pexidartinib that are mediated by CYP3A4/5, the major human phase I drug metabolizing enzymes. Using a synthetic ketone, we rule out the Baeyer-Villiger oxidation mechanism that is commonly invoked to address P450-mediated C-C bond cleavages. Our studies in 18O2 and H2 18O enriched systems reveal two unusual distinct mechanisms of C-C bond cleavage: one bond is cleaved by CYP3A-mediated ipso-addition of oxygen to a C(sp2) site of N-protected pyridin-2-amines, and the other occurs by a pseudo-retro-aldol reaction after hydroxylation of a C(sp3) site. This is the first report of CYP3A-mediated C-C bond cleavage in drug metabolism via ipso-addition of oxygen mediated mechanism. CYP3A-mediated ipso-addition is also implicated in the regioselective C-C cleavages of several pexidartinib analogs. The regiospecificity of CYP3A-catalyzed oxygen ipso-addition under environmentally friendly conditions may be attractive and inspire biomimetic or P450-engineering methods to address the challenging task of C-C bond cleavages.

Physiology education in China: the current situation and changes over the past 3 decades.

OBJECTIVE: As an experimental biological science, physiology has been taught as an integral component of medical curricula for a long time in China. The teaching effectiveness of physiology courses will directly affect students' learning of other medical disciplines. The purpose of this study is to investigate the current situation and changes in physiology teaching over 30 years in Chinese medical schools. METHODS: National survey was conducted online on the platform SoJump via WeChat and the web. The head of the physiology department in medical school was asked to indicate the information of physiology education from three periods: 1991-2000, 2001-2010, and 2011-2020. The responses of 80 leaders of the Department of Physiology from mainland Chinese medical schools were included in the study for analysis. RESULTS: The survey showed that the class hours, both of theory and practice, had been decreased. During the past 20 years, the total number of physiology teachers, the number of physiology teachers who had been educated in medical schools, and the number of technicians had been reduced, whereas teachers with doctor's degrees had been increased. In addition to traditional didactic teaching, new teaching approaches, including problem-based learning/case-based learning/team-based learning, integrated curriculum and formative evaluation systems, had been employed, mostly for more than 5 years, in some medical schools. CONCLUSION: The present study has provided historical data regarding the current status of physiology education in China and that in the past thirty years by showing that physiology education in China has developed quickly,even it faces many challenges.

General Anesthesia Exposure in Infancy and Childhood: A 10-year Bibliometric Analysis.

PURPOSE: Heated discussions have divided health care providers and policymakers on the risks versus benefits of general anesthesia in pediatric populations. We conducted this study to provide a comprehensive bibliometric analysis of general anesthesia in this specific population over the past decade. DESIGN: We summarized and quantitatively analyzed the studies related to general anesthesia in children and infants over the past decade. METHODS: Using the Web of Science Core Collection as the data source, we analyzed the literature using CiteSpace software, focusing on authors, countries, institutions, keywords, and references to identify hotspots and predict research trends. FINDINGS: A total of 2,364 publications on pediatric anesthesia were included in the analysis. The number of related publications and citations steadily increased from 2013 to 2022. The United States was the leading country in terms of output, and University of Toronto was the primary contributing institution. Co-citation analysis revealed that over the past decade research has mainly focused on the long-term adverse effects of general anesthesia on neurodevelopment and acute perioperative crisis events. Keyword analysis identified infant sedation and drug selection and compatibility as promising areas for development. In addition, improving the quality of perioperative anesthesia will be a major research focus in the future. CONCLUSIONS: Recent research in pediatric anesthesia has focused on mitigating the adverse effects of general anesthesia in infants and young children and studying the pharmacological compatibility of anesthetics. Our study results would assist researchers and clinicians in understanding the current research status and optimizing clinical practice in this field.

Increased gene dosage of RFWD2 causes autistic-like behaviors and aberrant synaptic formation and function in mice.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions, communication deficits and repetitive behaviors. A study of autistic human subjects has identified RFWD2 as a susceptibility gene for autism, and autistic patients have 3 copies of the RFWD2 gene. The role of RFWD2 as an E3 ligase in neuronal functions, and its contribution to the pathophysiology of ASD, remain unknown. We generated RFWD2 knockin mice to model the human autistic condition of high gene dosage of RFWD2. We found that heterozygous knockin (Rfwd2+/-) male mice exhibited the core symptoms of autism. Rfwd2+/- male mice showed deficits in social interaction and communication, increased repetitive and anxiety-like behavior, and spatial memory deficits, whereas Rfwd2+/- female mice showed subtle deficits in social communication and spatial memory but were normal in anxiety-like, repetitive, and social behaviors. These autistic-like behaviors in males were accompanied by a reduction in dendritic spine density and abnormal synaptic function on layer II/III pyramidal neurons in the prelimbic area of the medial prefrontal cortex (mPFC), as well as decreased expression of synaptic proteins. Impaired social behaviors in Rfwd2+/- male mice were rescued by the expression of ETV5, one of the major substrates of RFWD2, in the mPFC. These findings indicate an important role of RFWD2 in the pathogenesis of autism.

Design and construction of a refrigerator-cooled adiabatic calorimeter for heat capacity measurement in liquid helium temperature region.

Heat capacity is a fundamental thermodynamic property of a substance. Although heat capacity values and related thermodynamic functions are available for many materials, low-temperature heat capacity measurements, especially for novel materials, can still provide valuable insights for research in physics, chemistry, thermodynamics, and other fields. Reliable low-temperature heat capacity data are typically measured using classical adiabatic calorimeters, which use liquid helium as the refrigerant to provide a cryogenic environment for heat capacity measurements. However, liquid helium is not only expensive but also not easy to obtain, which greatly limits the application of adiabatic calorimetry. In this work, an accurate adiabatic calorimeter equipped with a Gifford-MacMahon refrigerator was designed and constructed for measuring the heat capacity of condensed matter in the temperature range from 4 to 100 K. The Gifford-MacMahon refrigerator was utilized to provide a stable liquid helium-free cryogenic environment. A simple mechanical thermal switch assembly was designed to facilitate switching between the refrigeration mode and the adiabatic measurement mode of the calorimeter. Based on the measurement results of standard reference materials, the optimized repeatability and accuracy of heat capacity measurements were determined to be within 0.8% and 1.5%, respectively. The heat capacity of α-Fe2O3 nanoparticles was also investigated with this device. Furthermore, this adiabatic calorimeter only requires electricity to operate in the liquid helium temperature range, which may significantly advance the research on low-temperature heat capacity based on adiabatic calorimetry.

Functional oral status and oral health-related quality of life in community-dwelling older adults in Singapore.

OBJECTIVES: The objectives were to investigate the association between oral functional status (defined by the number of functional teeth and functional occluding units [FOUs]) on oral health-related quality of life (OHRQoL). It also aimed to determine if dentures could compensate for the loss of FOUs in terms of OHRQoL in community-dwelling older adults in Singapore. METHODS: Community-dwelling older adults, aged 60 years and above, were recruited from a community-based oral health functional screening programme from 1 May 2018 to 31 December 2019. During the screening, an Oral Health Impact Profile-14 (OHIP-14) questionnaire and oral examination were administered. Statistical analysis was performed using the chi-square test, univariate logistic regression and multivariate predictive modelling. RESULTS: Data from 1037 participants were analysed (52% female; mean age 71.5 (SD 7.15)). The mean OHIP-14 score was 4.5 ± 7.2. The OHIP-14 scores were significantly associated with the number of functional teeth and the number of FOUs (p < .001). Having at least 20 functional teeth or 10 FOUs was associated with a significantly lower OHIP-14 score. Those with no FOUs had higher OHIP-14 scores compared to those with at least 10 FOUs, even in the presence of a satisfactory denture. CONCLUSION: Maintaining at least 20 functional teeth or 10 FOUs was associated with better OHRQoL among community-dwelling older adults in Singapore. Dentures may have limited compensatory ability in terms of replacing natural functional occlusal units and maintaining OHRQoL.

The origin of different bending stiffness between double-stranded RNA and DNA revealed by magnetic tweezers and simulations.

The subtle differences in the chemical structures of double-stranded (ds) RNA and DNA lead to significant variations in their biological roles and medical implications, largely due to their distinct biophysical properties, such as bending stiffness. Although it is well known that A-form dsRNA is stiffer than B-form dsDNA under physiological salt conditions, the underlying cause of this difference remains unclear. In this study, we employ high-precision magnetic-tweezer experiments along with molecular dynamics simulations and reveal that the relative bending stiffness between dsRNA and dsDNA is primarily determined by the structure- and salt-concentration-dependent ion distribution around their helical structures. At near-physiological salt conditions, dsRNA shows a sparser ion distribution surrounding its phosphate groups compared to dsDNA, causing its greater stiffness. However, at very high monovalent salt concentrations, phosphate groups in both dsRNA and dsDNA become fully neutralized by excess ions, resulting in a similar intrinsic bending persistence length of approximately 39 nm. This similarity in intrinsic bending stiffness of dsRNA and dsDNA is coupled to the analogous fluctuations in their total groove widths and further coupled to the similar fluctuation of base-pair inclination, despite their distinct A-form and B-form helical structures.

Timing of Caffeine Ingestion Does Not Improve Three-Point Shooting Accuracy in College Basketball Players.

This study investigated the effects of the timing of caffeine (3 mg/kg body mass) ingestion on three-point shooting accuracy and other performance parameters during a basketball exercise simulation test (BEST). Eighteen college basketball players (mean ± SD: age = 24.4 ± 1.5 years, height = 181.7 ± 9.5 cm, body mass = 80.9 ± 13.2 kg) underwent one familiarization trial and three main conditions in a randomized order: (a) placebo (maltodextrin) and placebo, (b) caffeine and placebo, and (c) placebo and caffeine. Participants ingested either the placebo or caffeine pill 75 and 15 min before performing four quarters of the BEST and a three-point shooting protocol. During each quarter, participants completed 16 rounds of the BEST and ten three-point shots. Vertical jump height, 6 m sprint timing, BEST completion timing, three-point shooting accuracy, heart rate, rate of perceived exertion, blood glucose, blood lactate, and psychological measures pertaining to performance were measured. The BEST completion timing differed among conditions (placebo and placebo = 26.4 ± 2.0 s, caffeine and placebo = 25.8 ± 2.0 s, placebo and caffeine = 25.9 ± 2.1 s; p = .031) but not three-point shooting accuracy (placebo and placebo = 12.33 ± 4.10; caffeine and placebo = 12.61 ± 2.81; placebo and caffeine = 11.67 ± 3.77; p = .648), vertical jump height, or sprint times. Manipulating ingestion timing of caffeine did not improve three-point shooting accuracy, vertical jump height, or 6 m sprint timings, but caffeine can improve performance times during simulated basketball exercise irrespective of ingestion timing.