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.

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.

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.

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.

Multifunctional Separator Enables High-Performance Sodium Metal Batteries in Carbonate-Based Electrolytes.

Sodium metal has become one of the most promising anodes for next-generation cheap and high-energy-density metal batteries; however, challenges caused by the uncontrollable sodium dendrite growth and fragile solid electrolyte interphase (SEI) restrict their large-scale practical applications in low-cost and wide-voltage-window carbonate electrolytes. Herein, a novel multifunctional separator with lightweight and high thinness is proposed, assembled by the cobalt-based metal-organic framework nanowires (Co-NWS), to replace the widely applied thick and heavy glass fiber separator. Benefitting from its abundant sodiophilic functional groups and densely stacked nanowires, Co-NWS not only exhibits outstanding electrolyte wettability and effectively induces uniform Na+ ion flux as a strong ion redistributor but also favors constructing the robust N,F-rich SEI layer. Satisfactorily, with 10 µL carbonate electrolyte, a Na|Co-NWS|Cu half-cell delivers stable cycling (over 260 cycles) with a high average Coulombic efficiency of 98%, and the symmetric cell shows a long cycle life of more than 500 h. Remarkably, the full cell shows a long-term life span (over 1500 cycles with 92% capacity retention) at high current density in the carbonate electrolyte. This work opens up a strategy for developing dendrite-free, low-cost, and long-life-span sodium metal batteries in carbonate-based electrolytes.

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.

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.

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.

Impact of Exercise Training Interventions on Flow-Mediated Dilation in Adults: An Umbrella Review.

BACKGROUND: Dysfunction of the endothelium is a key precursor of cardiovascular disease. Endothelial function, as assessed via the flow-mediated dilation test, is attenuated with chronic disease (e.g., type 2 diabetes mellitus, hypertension). Exercise training may mitigate this dysfunction and promote better vascular health. OBJECTIVE: The main objective of this umbrella review was to determine the impact of exercise training on flow-mediated dilation in healthy adults and those with chronic disease. METHODS: Studies were included if they conducted a systematic review and/or meta-analysis on flow-mediated dilation responses to exercise interventions in adults. Sources were searched in January 2022 and included Scopus, EMBASE, MEDLINE, CINAHL, and Academic Search Premier. National Institutes of Health quality assessment tools were used. The results were presented narratively. RESULTS: Twenty-seven systematic reviews, including 19 meta-analyses, (total: 5464 unique participants, 2181 reported unique female individuals) met the inclusion criteria. The average overall quality of included reviews was 8.8/11. The quality of studies within each included review varied from low to moderate using a variety of quality assessment scales. Reviews were conducted in healthy adults (n = 9, meta-analyses = 6), as well as those with type 2 diabetes (n = 5, meta-analyses = 4), cardiovascular conditions [i.e., conditions that impact the cardiovascular system, but excluding samples of only type 2 diabetes] (n = 11, meta-analyses = 7), and other chronic conditions (n = 2, meta-analyses = 2). Overall, the included reviews provided evidence that the type of training to optimally improve FMD may vary based on disease condition. Specifically, the evidence suggests that healthy adults benefitted most from higher intensity aerobic training and/or more frequent low-to-moderate resistance training. In addition, adults with type 2 diabetes benefitted most from low-intensity resistance or aerobic exercise training, whereas those with cardiovascular conditions should consider engaging in high-intensity aerobic training to improve endothelial function. CONCLUSIONS: This information may help guide the design of specific exercise programs or recommendations for adults with chronic conditions.

An acute bout of prolonged sitting blunts popliteal endothelium-independent dilation in young, healthy adults.

A single bout of prolonged uninterrupted sitting increases oxidative stress, reduces popliteal blood flow-induced shear stress, and diminishes endothelium-dependent, flow-mediated dilation (FMD). The FMD response is also influenced by the sensitivity of vascular smooth muscle cells to nitric oxide (i.e., endothelium-independent dilation), which is also attenuated by elevated oxidative stress. However, it is currently unknown whether prolonged sitting impacts popliteal endothelium-independent dilation responses, which may uncover a novel mechanism associated with sitting-induced vascular dysfunction. This study tested the hypothesis that prolonged sitting attenuates both popliteal FMD and endothelium-independent, nitroglycerin-mediated dilation responses (NMD, 0.4 mg sublingual dose). Popliteal blood flow (mL/min), relative FMD (%), and NMD (%) were assessed via duplex ultrasonography before and after a ∼3-h bout of sitting in 14 young, healthy adults (8♀; 22 ± 2 yr). Prolonged sitting attenuated resting blood flow (57 ± 23 to 32 ± 16 mL/min, P < 0.001), relative FMD (4.6 ± 2.8% to 2.2 ± 2.5%; P = 0.001), and NMD (7.3 ± 4.0% to 4.6 ± 3.0%; P = 0.002). These novel findings demonstrate that both endothelium-dependent and independent mechanisms contribute to the adverse vascular consequences associated with prolonged bouts of sitting.NEW & NOTEWORTHY We demonstrate that lower-limb vascular smooth muscle function is attenuated in young, healthy adults after an acute bout of prolonged sitting. These data indicate that prolonged sitting-induced vascular dysfunction involves both endothelium-dependent and -independent mechanisms.

2D Ag Ion-Loaded Anionic Nanosheets for Polymer-Based Film with Durable Antibacterial Activities.

Silver (Ag) has been demonstrated to have excellent performance to kill bacteria, fungi, and some viruses because it can release positively charged Ag ions with highly antibacterial and antifungal activities. However, effectively controlling the slow release of Ag ions is the key to preparing high-performance Ag-based antibacterial agents, which remains a challenge. In this work, we have developed a new Ag-based antibacterial agent composed of Ag ions loaded on 2D anionic 2D Sb3P2O14 3- nanosheets (denoted as Ag-Sb3P2O14). 2D anionic nanosheets not only adsorb a large amount of Ag ions but also control their slow release through electrostatic interaction between nanosheets and Ag ions. 2D Ag-Sb3P2O14 nanofillers enable excellent high antibacterial activities for the poly(vinylidene fluoride) (PVDF) film composites against microorganisms including Escherichia coli and Staphylococcus aureus. Moreover, the PVDF membrane with 5 wt % 2D Ag-Sb3P2O14 nanofillers can kill almost all bacterial after 50 times washing, demonstrating its excellent durable antibacterial activities. This work opens up a new and promising route to durable Ag-based antibacterial agents for polymer-based composites.

Corrigendum: brain microvascular endothelial cell-derived HMGB1 facilitates monocyte adhesion and transmigration to promote JEV neuroinvasion.

[This corrects the article DOI: 10.3389/fcimb.2021.701820.].

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.

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.

Corrigendum: Brain Microvascular Endothelial Cell-Derived HMGB1 Facilitates Monocyte Adhesion and Transmigration to Promote JEV Neuroinvasion.

[This corrects the article DOI: 10.3389/fcimb.2021.701820.].

Brain Microvascular Endothelial Cell-Derived HMGB1 Facilitates Monocyte Adhesion and Transmigration to Promote JEV Neuroinvasion.

Infection with Japanese encephalitis virus (JEV) induces high morbidity and mortality, including potentially permanent neurological sequelae. However, the mechanisms by which viruses cross the blood-brain barrier (BBB) and invade into the central nervous system (CNS) remain unclear. Here, we show that extracellular HMGB1 facilitates immune cell transmigration. Furthermore, the migration of immune cells into the CNS dramatically increases during JEV infection which may enhance viral clearance, but paradoxically expedite the onset of Japanese encephalitis (JE). In this study, brain microvascular endothelial cells (BMECs) were utilized for the detection of HMGB1 release, and leucocyte, adhesion, and the integrity of the BBB in vitro. Genetically modified JEV-expressing EGFP (EGFP-JEV) and the BBB model were established to trace JEV-infected immune cell transmigration, which mimics the process of viral neuroinfection. We find that JEV causes HMGB1 release from BMECs while increasing adhesion molecules. Recombinant HMGB1 enhances leukocyte-endothelium adhesion, facilitating JEV-infected monocyte transmigration across endothelia. Thus, JEV successfully utilizes infected monocytes to spread into the brain, expanding inside of the brain, and leading to the acceleration of JE onset, which was facilitated by HMGB1. HMGB1-promoted monocyte transmigration may represent the mechanism of JEV neuroinvasion, revealing potential therapeutic targets.