Sitting knee-flexion angle does not influence endothelial-dependent vasodilation in laboratory or free-living conditions.

INTRODUCTION: Single bouts of prolonged bent-legged sitting attenuate popliteal endothelial-dependent vasodilation (as assessed via flow-mediated dilation [FMD]), which is partially attributed to arterial 'kinking'. However, the impact of knee-flexion angle on sitting-induced popliteal FMD is unknown. The objective of this study was to perform separate laboratory and free-living studies to test the hypotheses that: (1) popliteal FMD impairments would be graded between knee flexions at 90° (bent-legged sitting) > 45° > 0° (straight-legged sitting) following a 3-hour bout of sitting; and (2) more habitual time spent bent-legged sitting (< 45°) would be associated with lower FMD. METHODS: The laboratory study included eight young, healthy adults (24 ± 2 years; four women) who underwent two sitting bouts over 2 days with one leg positioned at a knee-flexion angle of 0° or 90° and the opposite leg at 45° knee flexion. Popliteal FMD was assessed at pre- and postsitting timepoints. RESULTS: Sitting-induced reductions in FMD were similar between all knee-flexion angles (all, p > 0.674). The free-living study included 35 young, healthy adults (23 ± 3 years; 16 women) who wore three activPAL monitors (torso, thigh, shin) to determine detailed sedentary postures. Time spent sedentary (624 ± 127 min/day), straight-legged sitting (112 ± 98 min/day), and bent-legged sitting (442 ± 106 min/day) were not related to relative FMD (5.3 ± 1.8%; all, p > 0.240). CONCLUSION: These findings suggest that knee-flexion angle-mediated arterial 'kinking' during sitting is not a major contributor toward sitting-induced popliteal endothelial-dependent vasodilatory dysfunction.

Effectiveness of contrast-enhanced duplex ultrasound for detecting renal artery stenosis: A systematic review.

PURPOSE: Contrast-enhanced duplex ultrasound (CEUS) might be a useful tool to diagnosing renal artery stenosis (RAS). We amalgamated and reviewed the evidence assessing the diagnostic accuracy of CEUS on detecting RAS compared to angiography. METHODS: This preregistered systematic review included studies that compared the presence of RAS via CEUS with angiography. Sources were searched in November 2022 and included Scopus, EMBASE, MEDLINE, CINAHL, and Academic Search Premier (n = 1717). The Quality Assessment of Diagnostic Studies 2 tool assessed study quality. Results are presented narratively. RESULTS: The studies included (n = 11) had a total of 447 unique participants (193 females) and average age of 56 ± 9 years. Five of eleven studies investigated CEUS using SonoVue contrast agent and reported an average accuracy (91% ± 2%), sensitivity (91% ± 3%), specificity (90% ± 5%), negative predictive value (86% ± 6%), and positive predictive value (94% ± 1%) with all values >80%. The accuracy of CEUS using other types of contrast agent (n = 6), including Levovsit (n = 3/6), Definity (n = 1/6), perfienapent emulsion (n = 1/6), and perfluorocarbon-exposed sonicated dextrose albumin (n = 1/6) was mixed. These studies detected an average accuracy of 91 ± 11% (n = 2/3% > 80%), sensitivity of 98% ± 4%, (n = 3/3% > 80%), and specificity of 86% ± 10% (n = 2/3% > 80%). Included studies had generally low risk of bias and applicability concerns except for unclear flow and timing (n = 7/11) and applicability of patient selection (n = 4/11). CONCLUSION: Despite being limited by the heterogeneity of included studies, our review indicates a high overall diagnostic accuracy for CEUS to detect RAS compared to angiography, with the largest evidence-base for SonoVue contrast. Radiologists and hospital decision makers should consider CEUS as an acceptable alternative to angiography.

A Dual Organic Solvent Zn-Ion Electrolyte Enables Highly Stable Zn Metal Batteries.

Aqueous zinc (Zn) batteries have been regarded as an alternative to lithium-ion batteries due to their high abundance, low cost, and higher intrinsic safety. However, the low Zn plating/stripping reversibility, Zn dendrite growth, and continuous water consumption have hindered the practical application of aqueous Zn anodes. Herein, a hydrous organic Zn-ion electrolyte based on a dual organic solvent, namely hydrated Zn(BF4)2 zinc salt dissolved in dimethyl carbonate (DMC) and vinyl carbonate (EC) solvents [denoted as Zn(BF4)2/DMC/EC], can address these problems, which not only inhibits the side reactions but also promotes uniform Zn plating/stripping through the formation of a stable solid state interface layer and Zn2+-EC/2DMC pairs. This electrolyte enables the Zn electrode to stably undergo >700 cycles at a rate of 1 mA cm-2 with a Coulombic efficiency of 99.71%. Moreover, the full cell paired with V2O5 also demonstrates excellent cycling stability without capacity decay at 1 A g-1 after 1600 cycles.

Is the Mutation Rate Lower in Genomic Regions of Stronger Selective Constraints?

A study of the plant Arabidopsis thaliana detected lower mutation rates in genomic regions where mutations are more likely to be deleterious, challenging the principle that mutagenesis is blind to its consequence. To examine the generality of this finding, we analyze large mutational data from baker's yeast and humans. The yeast data do not exhibit this trend, whereas the human data show an opposite trend that disappears upon the control of potential confounders. We find that the Arabidopsis study identified substantially more mutations than reported in the original data-generating studies and expected from Arabidopsis' mutation rate. These extra mutations are enriched in polynucleotide tracts and have relatively low sequencing qualities so are likely sequencing errors. Furthermore, the polynucleotide "mutations" can produce the purported mutational trend in Arabidopsis. Together, our results do not support lower mutagenesis of genomic regions of stronger selective constraints in the plant, fungal, and animal models examined.

Impact of exercise training on pulse wave velocity in healthy and clinical populations: a systematic review of systematic reviews.

Elevated pulse wave velocity (PWV) determined arterial stiffness is a prominent marker of cardiovascular disease (CVD) risk. Exercise training delays the progression of CVD, but existing reviews on the impact of training on PWV are conflicting. We synthesized the evidence on the effects of exercise training interventions on PWV. We searched Scopus, EMBASE, PubMed, CINAHL, and Academic Search Premier databases for systematic reviews including PWV, and examined the effects of exercise training on PWV. We screened 842 citations that resulted in 44 systematic reviews, including 22 meta-analyses [unique participants, n = 6,719 (3,390 females)]. Studies were conducted in general adults with/without disease(s) (n = 19, 8 meta-analyses), kidney disease (n = 9, 6 meta-analyses), increased CVD risk or CVD (n = 7, 5 meta-analyses), type 2 diabetes mellitus (n = 3, 2 meta-analyses), and other conditions (n = 6, 2 meta-analyses). In general adults, PWV was reduced by aerobic exercise (ß, -0.75 to -0.52 m/s) and low-to-moderate intensity resistance exercise training (ß, -0.34 m/s). Exercise training was beneficial for patients with kidney disease (ß, -1.13 to -0.56 m/s). Aerobic exercise improved PWV in adults with CVD or high CVD risk (ß, -0.70 to -0.42 m/s). Combined aerobic and resistance exercise training decreased carotid-femoral (CF) PWV in patients with CVD (ß, -1.15 m/s) and decreased brachial-ankle (BA) PWV in postmenopausal females (ß, -1.18 m/s). Neither aerobic nor combined training improved PWV in individuals with type 2 diabetes. The potential physiological mechanisms involved are discussed. Overall, the included systematic reviews and meta-analyses documented that exercise training was an effective strategy to improve PWV, but the optimal type of training varied between populations.

Genomic estimates of mutation and substitution rates contradict the evolutionary speed hypothesis of the latitudinal diversity gradient.

The latitudinal diversity gradient (LDG) refers to a decrease in biodiversity from the equator to the poles. The evolutionary speed hypothesis, backed by the metabolic theory of ecology, asserts that nucleotide mutation and substitution rates per site per year are higher and thereby speciation rates are higher at higher temperatures, generating the LDG. However, prior empirical investigations of the relationship between the temperature and mutation or substitution rate were based on a few genes and the results were mixed. We here revisit this relationship using genomic data. No significant correlation between the temperature and mutation rate is found in 13 prokaryotes or in 107 eukaryotes. An analysis of 234 diverse trios of bacterial taxa indicates that the synonymous substitution rate is not significantly associated with the growth temperature. The same data, however, reveal a significant negative association between the nonsynonymous substitution rate and temperature, which is explainable by a larger fraction of detrimental nonsynonymous mutations at higher temperatures due to a stronger demand for protein stability. We conclude that the evolutionary speed hypothesis of the LDG is unsupported by genomic data and advise that future mechanistic studies of the LDG should focus on other hypotheses.

Recent Progress on Fe-Based Single/Dual-Atom Catalysts for Zn-Air Batteries.

As one of the most competitive candidates for large-scale energy storage, zinc-air batteries (ZABs) have attracted great attention due to their high theoretical specific energy density, low toxicity, high abundance, and high safety. It is highly desirable but still remains a huge challenge, however, to achieve cheap and efficient electrocatalysts to promote their commercialization. Recently, Fe-based single-atom and dual-atom catalysts (SACs and DACs, respectively) have emerged as powerful candidates for ZABs derived from their maximum utilization of atoms, excellent catalytic performance, and low price. In this review, some fundamental concepts in the field of ZABs are presented and the recent progress on the reported Fe-based SACs and DACs is summarized, mainly focusing on the relationship between structure and performance at the atomic level, with the aim of providing helpful guidelines for future rational designs of efficient electrocatalysts with atomically dispersed active sites. Finally, the great advantages and future challenges in this field of ZABs are also discussed.

Higher Germline Mutagenesis of Genes with Stronger Testis Expressions Refutes the Transcriptional Scanning Hypothesis.

Why are more genes expressed in the testis than in any other organ in mammals? The recently proposed transcriptional scanning hypothesis posits that transcription alleviates mutagenesis through transcription-coupled repair so has been selected in the testis to modulate the germline mutation rate in a gene-specific manner. Here, we show that this hypothesis is theoretically untenable because the selection would be too weak to have an effect in mammals. Furthermore, the analysis purported to support the hypothesis did not control known confounding factors and inappropriately excluded genes with no observed de novo mutations. After remedying these problems, we find the human germline mutation rate of a gene to rise with its testis expression level. This trend also exists for inferred coding strand-originated mutations, suggesting that it arises from transcription-associated mutagenesis. Furthermore, the testis expression level of a gene robustly correlates with its overall expression in other organs, nullifying the need to explain the testis silencing of a minority of genes by adaptive germline mutagenesis. Taken together, our results demonstrate that human testis transcription increases the germline mutation rate, rejecting the transcriptional scanning hypothesis of extensive gene expressions in the mammalian testis.

Does aerobic fitness impact prolonged sitting-induced popliteal artery endothelial dysfunction?

PURPOSE: Acute prolonged bouts of sitting reduce popliteal artery blood flow and flow-mediated dilation (FMD). Individuals with higher aerobic fitness have enhanced popliteal FMD. Conflicting evidence regarding whether more aerobically fit individuals are protected from the negative impacts of sitting on popliteal endothelial function in male-dominated studies have been reported. We further explored the relationship between aerobic fitness and sitting-induced impairments in popliteal blood flow and FMD in a more sex-balanced cohort. METHODS: Relative peak oxygen consumption (V̇O2peak) was assessed using a cycling-based incremental test in 21 healthy adults (eight males; 23 ± 2 years; 23.9 ± 2.9 kg/m2). Popliteal blood flow and relative FMD (%) were measured via duplex ultrasonography before and after 3 h of uninterrupted sitting. Pearson correlations were performed separately between V̇O2peak versus pre-sitting and sitting-induced reductions in popliteal outcomes. RESULTS: Aerobic fitness (41.0 ± 9.7 ml/kg/min) was positively correlated with pre-sitting popliteal blood flow (65 ± 23 mL/min; R = 0.59, P = 0.005) and relative FMD (4.2 ± 1.5%; R = 0.49, P = 0.03). As expected, sitting reduced resting blood flow (19 ± 11 mL/min) and FMD (1.9 ± 0.7%) (both, P < 0.001). V̇O2peak was inversely related to sitting-induced declines in blood flow (Δ-46 ± 23 mL/min; R = - 0.71, P < 0.001) and FMD (Δ-2.4 ± 1.5%; R = - 0.51, P = 0.02). CONCLUSIONS: Although higher aerobic fitness was associated with more favorable popliteal endothelial-dependent vasodilator responses, it also corresponded with larger sitting-induced impairments in FMD. This suggests that being more aerobically fit does not protect against sitting-induced vascular endothelial dysfunction. As such, all young adults should minimize habitual prolonged sedentary bouts, regardless of their aerobic fitness level.

Evolution of the Yeast Recombination Landscape.

Meiotic recombination comprises crossovers and noncrossovers. Recombination, crossover in particular, shuffles mutations and impacts both the level of genetic polymorphism and the speed of adaptation. In many species, the recombination rate varies across the genome with hot and cold spots. The hotspot paradox hypothesis asserts that recombination hotspots are evolutionarily unstable due to self-destruction. However, the genomic landscape of double-strand breaks (DSBs), which initiate recombination, is evolutionarily conserved among divergent yeast species, casting doubt on the hotspot paradox hypothesis. Nonetheless, because only a subset of DSBs are associated with crossovers, the evolutionary conservation of the crossover landscape could differ from that of DSBs. Here, we investigate this possibility by generating a high-resolution recombination map of the budding yeast Saccharomyces paradoxus through whole-genome sequencing of 50 meiotic tetrads and by comparing this recombination map with that of S. cerevisiae. We observe a 40% lower recombination rate in S. paradoxus than in S. cerevisiae. Compared with the DSB landscape, the crossover landscape is even more conserved. Further analyses indicate that the elevated conservation of the crossover landscape is explained by a near-subtelomeric crossover preference in both yeasts, which we find to be attributable at least in part to crossover interference. We conclude that the yeast crossover landscape is highly conserved and that the evolutionary conservation of this landscape can differ from that of the DSB landscape.

Atomically Dispersed Molybdenum Catalysts for Efficient Ambient Nitrogen Fixation.

NH3 synthesis by the electrocatalytic N2 reduction reaction (NRR) under ambient conditions is an appealing alternative to the currently employed industrial method-the Haber-Bosch process-that requires high temperature and pressure. We report single Mo atoms anchored to nitrogen-doped porous carbon as a cost-effective catalyst for the NRR. Benefiting from the optimally high density of active sites and hierarchically porous carbon frameworks, this catalyst achieves a high NH3 yield rate (34.0±3.6 µg NH 3 h-1 mgcat. -1 ) and a high Faradaic efficiency (14.6±1.6 %) in 0.1 m KOH at room temperature. These values are considerably higher compared to previously reported non-precious-metal electrocatalysts. Moreover, this catalyst displays no obvious current drop during a 50 000 s NRR, and high activity and durability are achieved in 0.1 m HCl. The findings provide a promising lead for the design of efficient and robust single-atom non-precious-metal catalysts for the electrocatalytic NRR.

Direct Determination of the Mutation Rate in the Bumblebee Reveals Evidence for Weak Recombination-Associated Mutation and an Approximate Rate Constancy in Insects.

Accurate knowledge of the mutation rate provides a base line for inferring expected rates of evolution, for testing evolutionary hypotheses and for estimation of key parameters. Advances in sequencing technology now permit direct estimates of the mutation rate from sequencing of close relatives. Within insects there have been three prior such estimates, two in nonsocial insects (Drosophila: 2.8 × 10-9 per bp per haploid genome per generation; Heliconius: 2.9 × 10-9) and one in a social species, the honeybee (3.4 × 10-9). Might the honeybee's rate be ∼20% higher because it has an exceptionally high recombination rate and recombination may be directly or indirectly mutagenic? To address this possibility, we provide a direct estimate of the mutation rate in the bumblebee (Bombus terrestris), this being a close relative of the honeybee but with a much lower recombination rate. We confirm that the crossover rate of the bumblebee is indeed much lower than honeybees (8.7 cM/Mb vs. 37 cM/Mb). Importantly, we find no significant difference in the mutation rates: we estimate for bumblebees a rate of 3.6 × 10-9 per haploid genome per generation (95% confidence intervals 2.38 × 10-9 and 5.37 × 10-9) which is just 5% higher than the estimate that of honeybees. Both genomes have approximately one new mutation per haploid genome per generation. While we find evidence for a direct coupling between recombination and mutation (also seen in honeybees), the effect is so weak as to leave almost no footprint on any between-species differences. The similarity in mutation rates suggests an approximate constancy of the mutation rate in insects.

Highly Active, Durable Ultrathin MoTe2 Layers for the Electroreduction of CO2 to CH4.

The electroreduction of CO2 to CH4 is a highly desirable, challenging research topic. In this study, an electrocatalytic system comprising ultrathin MoTe2 layers and an ionic liquid electrolyte for the reduction of CO2 to methane is reported, efficiently affording methane with a faradaic efficiency of 83 ± 3% (similar to the best Cu-based catalysts reported thus far) and a durable activity of greater than 45 h at a relatively high current density of 25.6 mA cm-2 (-1.0 VRHE ). The results obtained can facilitate research on the design of other transition-metal dichalcogenide electrocatalysts for the reduction of CO2 to valuable fuels.

Potential-Cycling Synthesis of Single Platinum Atoms for Efficient Hydrogen Evolution in Neutral Media.

Single-atom catalysts (SACs) have exhibited high activities for the hydrogen evolution reaction (HER) electrocatalysis in acidic or alkaline media, when they are used with binders on cathodes. However, to date, no SACs have been reported for the HER electrocatalysis in neutral media. We demonstrate a potential-cycling method to synthesize a catalyst comprising single Pt atoms on CoP-based nanotube arrays supported by a Ni foam, termed PtSA-NT-NF. This binder-free catalyst is centimeter-scale and scalable. It is directly used as HER cathodes, whose performances at low and high current densities in phosphate buffer solutions (pH 7.2) are comparable to and better than, respectively, those of commercial Pt/C. The Pt mass activity of PtSA-NT-NF is 4 times of that of Pt/C, and its electrocatalytic stability is also better than that of Pt/C. This work provides a large-scale production strategy for binder-free Pt SAC electrodes for efficient HER in neutral media.

High genetic abundance of Rpi-blb2/Mi-1.2/Cami gene family in Solanaceae.

BACKGROUND: Three NBS-LRR genes, Rpi-blb2, Mi-1.2, and Cami, constitute a very special plant resistance gene family. These genes confer resistance against 4 distantly related pathogen species in 3 different Solanaceae hosts. To characterize this noted resistance, we conducted a series of studies on this gene family. RESULTS: First, homologs of this gene family were identified in the pepper, tomato and potato genomes. This revealed a large variation in copy number within this gene family among species and a great divergence was found both between and within species. To gain more information pertaining to gene resistance within this family, 121 LRR regions were cloned in 16 different wild/cultivated potato accessions. Again, frequent copy number variations and a high level of divergence between homolog were observed common among accessions. The divergence within species was so high that it reaches the level of divergence between species. Also, frequent frameshift mutations and abundant gene conversion events were identified in these LRR regions. CONCLUSIONS: Our findings suggest that this family harbors an unusually high level of genetic abundance, making it of particular interest. Together with other reported examples, our study also provides evidence that multi-resistance is a common trait in R gene families like this.

Great majority of recombination events in Arabidopsis are gene conversion events.

The evolutionary importance of meiosis may not solely be associated with allelic shuffling caused by crossing-over but also have to do with its more immediate effects such as gene conversion. Although estimates of the crossing-over rate are often well resolved, the gene conversion rate is much less clear. In Arabidopsis, for example, next-generation sequencing approaches suggest that the two rates are about the same, which contrasts with indirect measures, these suggesting an excess of gene conversion. Here, we provide analysis of this problem by sequencing 40 F(2) Arabidopsis plants and their parents. Small gene conversion tracts, with biased gene conversion content, represent over 90% (probably nearer 99%) of all recombination events. The rate of alteration of protein sequence caused by gene conversion is over 600 times that caused by mutation. Finally, our analysis reveals recombination hot spots and unexpectedly high recombination rates near centromeres. This may be responsible for the previously unexplained pattern of high genetic diversity near Arabidopsis centromeres.

A new era of mutation rate analyses: Concepts and methods.

The mutation rate is a pivotal biological characteristic, intricately governed by natural selection and historically garnering considerable attention. Recent advances in high-throughput sequencing and analytical methodologies have profoundly transformed our understanding in this domain, ushering in an unprecedented era of mutation rate research. This paper aims to provide a comprehensive overview of the key concepts and methodologies frequently employed in the study of mutation rates. It examines various types of mutations, explores the evolutionary dynamics and associated theories, and synthesizes both classical and contemporary hypotheses. Furthermore, this review comprehensively explores recent advances in understanding germline and somatic mutations in animals and offers an overview of experimental methodologies, mutational patterns, molecular mechanisms, and driving forces influencing variations in mutation rates across species and tissues. Finally, it proposes several potential research directions and pressing questions for future investigations.

A Single Bout of Prolonged Sitting Augments Very Short-Term Blood Pressure Variability.

BACKGROUND: More habitual time spent engaging in prolonged sedentary behaviours increases the risk of developing hypertension. Beat-by-beat systolic (SBPV) and diastolic blood pressure variability (DBPV) are more pronounced in persons with hypertension and may be an early manifestation of blood pressure dysregulation. We tested the hypothesis that a single bout of prolonged sitting augments very short-term SBPV and DBPV. The secondary aim was to explore sex differences in prolonged sitting-induced increases in SBPV and DBPV. METHODS: Thirty-three adults (22.9±1.9 years; 17 females) completed a single, 3-hr bout of prolonged sitting with beat-by-beat arterial pressure determined at baseline, 1.5-hr, and 3-hr via finger photoplethysmography. RESULTS: There were no sex differences observed for baseline brachial SBP (males: 122±10 mmHg; females: 111±9 mmHg), SBPV (males: 1.87±0.63 mmHg; females: 1.51±0.38 mmHg), DBP (males: 68±6 mmHg; females: 66±8 mmHg), or DBPV (males: 1.40±0.41 mmHg; females: 1.27±0.32 mmHg) (all, p>0.41). In the pooled sample, baseline SBPV (1.68±0.54 mmHg) remained unchanged after 1.5-hr (1.80±0.60 mmHg; p=0.59), but increased after 3.0-hr (1.84±0.52 mmHg; p=0.01). This post-sitting increase was driven by males (p=0.009), with no difference observed in females (p=1.00). Similarly, baseline DBPV (1.33±0.36 mmHg) was similar after 1.5-hr (1.42±0.41 mmHg; p=0.72) but was increased at 3-hr (1.50±0.34 mmHg; p=0.02). However, no sex differences in DBPV (all, p>0.07) were observed across the time points. CONCLUSIONS: In young, normotensive adults, a single bout of prolonged sitting augmented beat-by-beat blood pressure variability, which may provide a link between uninterrupted sitting and the development of blood pressure dysregulation.

High-Humidity-Tolerant Chloride Solid-State Electrolyte for All-Solid-State Lithium Batteries.

Halide solid-state electrolytes (SSEs) hold promise for the commercialization of all-solid-state lithium batteries (ASSLBs); however, the currently cost-effective zirconium-based chloride SSEs suffer from hygroscopic irreversibility, low ionic conductivity, and inadequate thermal stability. Herein, a novel indium-doped zirconium-based chloride is fabricated to satisfy the abovementioned requirements, achieving outstanding-performance ASSLBs at room temperature. Compared to the conventional Li2ZrCl6 and Li3InCl6 SSEs, the hc-Li2+xZr1-xInxCl6 (0.3 ≤ x ≤ 1) possesses higher ionic conductivity (up to 1.4 mS cm-1), and thermal stability (350 °C). At the same time, the hc-Li2.8Zr0.2In0.8Cl6 also shows obvious hygroscopic reversibility, where its recovery rate of the ionic conductivity is up to 82.5% after 24-h exposure in the 5% relative humidity followed by heat treatment. Theoretical calculation and experimental results reveal that those advantages are derived from the lattice expansion and the formation of Li3InCl6 ·2H2O hydrates, which can effectively reduce the migration energy barrier of Li ions and offer reversible hydration/dehydration pathway. Finally, an ASSLB, assembled with reheated-Li2.8Zr0.2In0.8Cl6 after humidity exposure, single-crystal LiNi0.8Mn0.1Co0.1O2 and Li-In alloy, exhibits capacity retention of 71% after 500 cycles under 1 C at 25 °C. This novel high-humidity-tolerant chloride electrolyte is expected to greatly carry forward the ASSLBs industrialization.