Two-Dimensional Spin-Crossover Molecular Solid Solutions with Tunable Transition Temperatures across 90 K.

Spin-crossover (SCO) materials exhibit remarkable potential as bistable switches in molecular devices. However, the spin transition temperatures (Tc) of known compounds are unable to cover the entire ambient temperature spectrum, largely limiting their practical utility. This study reports an exemplary two-dimensional SCO solid solution system, [FeIII(H0.5LCl)2-2x(H0.5LF)2x]·H2O (H0.5LX = 5-X-2-hydroxybenzylidene-hydrazinecarbothioamide, X = F or Cl, x = 0 to 1), in which the adjacent layers are adhered via hydrogen bonding. Notably, the Tc of this system can be fine-tuned across 90 K (227-316 K) in a linear manner by modulating the fraction x of the LF ligand. Elevating x results in strengthened hydrogen bonding between adjacent layers, which leads to enhanced intermolecular interactions between adjacent SCO molecules. Single-crystal diffraction analysis and periodic density functional theory calculations revealed that such a special kind of alteration in interlayer interactions strengthens the FeIIIN2O2S2 ligand field and corresponding SCO energy barrier, consequently resulting in increased Tc. This work provides a new pathway for tuning the Tc of SCO materials through delicate manipulation of molecular interactions, which could expand the application of bistable molecular solids to a much wider temperature regime.

A high-fidelity long-read sequencing-based approach enables accurate and effective genetic diagnosis of spinal muscular atrophy.

BACKGROUND: We aimed to develop a high-fidelity long-read sequencing (LRS)-based approach to detect SMN gene variants in one step. It is challenging for conventional step-wise methods to simultaneously detect all kinds of variations between homologous SMN1 and SMN2. METHODS: In this study, LRS was developed to analyze copy numbers (CNs), full sequences, and structure of SMN1 and SMN2. The results were compared with those from the step-wise methods in 202 samples from 67 families. RESULTS: LRS achieved 100% (202/202) and 99.5% (201/202) accuracy for SMN1 and SMN2 CNs, respectively. It corrected SMN1 CNs from MLPA, which was caused by SNVs/indels that located in probe-binding region. LRS identified 23 SNVs/indels distributing throughout SMN1, including c.22dup and c.884A > T in trans-configuration, and a de novo variant c.41_42delinsC for the first time. LRS also identified a SMN2 variant c.346A > G. Moreover, it successfully determined Alu-mediated 8978-bp deletion encompassing exon 2a-5 and 1415-bp deletion disrupting exon 1, and the exact breakpoints of large deletions. Through haplotype-based pedigree trio analysis, LRS identified SMN1 2 + 0 carriers, and determined the distribution of SMN1 and SMN2 on two chromosomes. CONCLUSIONS: LRS represents a more comprehensive and accurate diagnosis approach that is beneficial to early treatment and effective management of SMA.

Physical exercise ameliorates age-related deterioration of skeletal muscle and mortality by activating Pten-related pathways in Drosophila on a high-salt diet.

The phosphatase and tensin congeners (Pten) gene affects cell growth, cell proliferation, and rearrangement of connections, and it is closely related to cellular senescence, but it remains unclear the role of muscle-Pten gene in exercise against age-related deterioration in skeletal muscle and mortality induced by a high-salt diet (HSD). In here, overexpression and knockdown of muscle Pten gene were constructed by building MhcGAL4 /PtenUAS-overexpression and MhcGAL4 /PtenUAS-RNAi system in flies, and flies were given exercise training and a HSD for 2 weeks. The results showed that muscle Pten knockdown significantly reduced the climbing speed, climbing endurance, GPX activity, and the expression of Pten, Sirt1, PGC-1α genes, and it significantly increased the expression of Akt and ROS level, and impaired myofibril and mitochondria of aged skeletal muscle. Pten knockdown prevented exercise from countering the HSD-induced age-related deterioration of skeletal muscle. Pten overexpression has the opposite effect on skeletal muscle aging when compared to it knockdown, and it promoted exercise against HSD-induced age-related deterioration of skeletal muscle. Pten overexpression significantly increased lifespan, but its knockdown significantly decreased lifespan of flies. Thus, current results confirmed that differential expression of muscle Pten gene played an important role in regulating skeletal muscle aging and lifespan, and it also affected the adaptability of aging skeletal muscle to physical exercise since it determined the activity of muscle Pten/Akt pathway and Pten/Sirt1/PGC-1α pathway.

On-board measurements of OC/EC ratio, mixing state, and light absorption of ship-emitted particles.

Carbonaceous aerosols play important roles in environmental impacts and climate effects. The characteristics of ship-emitted carbonaceous aerosols keep unclear under the latest global low sulfur fuel oil policy. This study selected four ocean-going vessels burning low sulfur fuel oils for on-board exhaust testing. The emission factors of ship carbonaceous aerosols were obtained under different engine types (main and auxiliary engines), fuel types, and engine loads. Our results showed that fuel and engine types were both important factors affecting carbonaceous aerosol emissions for ship engines. The emission factors of OC and EC from main engines were 1.18 ± 0.62 and 0.06 ± 0.04 g/kg burning heavy fuel oil (HFO), while 0.52 ± 0.35 and 0.04 ± 0.03 g/kg burning marine gas oil (MGO), respectively. The OC/EC ratios of ship-emitted particles were within a large range of 2 to 23. The OC/EC ratios from the main engines were significantly higher than those from the auxiliary engines by a factor of 6.3. The result of chemical mixing states of ship-emitted particles observed by a single particle mass spectrometer (SPAMS) showed that OC and EC were internally mixed and existed as the ECOC-bonded forms in single particles. The measured light absorption of ship-emitted particles with higher OC/EC ratios showed an evident short-wave absorption enhancement based on the aethalometer AE-33. Our results implied that ship-emitted carbonaceous aerosols (especially with high OC/EC ratios) could not be uniformly treated regarding the optical properties to more precisely estimate their potential environmental impacts and climate effects in model systems in the future.

Role of muscle FOXO gene in exercise against the skeletal muscle and cardiac age-related defects and mortality caused by high-salt intake in Drosophila.

FOXO has long been associated with aging, exercise, and tissue homeostasis, but it remains unclear what the role is of the muscle FOXO gene in E against high-salt intake(HSI)-induced age-related defects of the skeletal muscle, heart, and mortality. In this research, overexpression and RNAi of the FOXO gene in the skeletal and heart muscle of Drosophila were constructed by building Mhc-GAL4/FOXO-UAS-overexpression and Mhc-GAL4/FOXO-UAS-RNAi system. The skeletal muscle and heart function, the balance of oxidation and antioxidant, and mitochondrial homeostasis were measured. The results showed that exercise reversed the age-related decline in climbing ability and downregulation of muscle FOXO expression induced by HSI. Muscle-specific FOXO-RNAi (FOXO-RNAi) and -overexpression (FOXO-OE) promoted or slowed the age-related decline in climbing ability, heart function, and skeletal muscle and heart structure damage, which was accompanied by the inhibition or activation of FOXO/PGC-1α/SDH and FOXO/SOD pathway activity, and oxidative stress (ROS) increased or decreased in both skeletal muscle and heart. The protective effect of exercise on the skeletal muscle and heart was blocked by FOXO-RNAi in aged HSI flies. FOXO-OE prolonged its lifespan, but it did not resist the HSI-induced lifespan shortening. Exercise did not improve HSI-induced lifespan shortening in FOXO-RNAi flies. Therefore, current results confirmed that the muscle FOXO gene played a vital role in exercise against age-related defects of the skeletal muscle and heart induced by HSI because it determined the activity of muscle FOXO/SOD and FOXO/PGC-1α/SDH pathways. The muscle FOXO gene also played an important role in exercise against HSI-induced mortality in aging flies.

Muscle FOXO-Specific Overexpression and Endurance Exercise Protect Skeletal Muscle and Heart from Defects Caused by a High-Fat Diet in Young Drosophila.

BACKGROUND: Obesity appears to significantly reduce physical activity, but it remains unclear whether this is related to obesity-induced damage to skeletal muscle (SM) and heart muscle (HM). Endurance exercise (EE) reduces obesity-induced defects in SM and HM, but its molecular mechanism is poorly understood. METHODS: The UAS/GAL4 system was used to construct the regulation of SM-specific FOXO gene expression in Drosophila, and the transgenic drosophila was subjected to EE and high-fat diet (HFD) intervention. RESULTS: The structure and function of SM and HM were impaired by a HFD and muscle-FOXO-specific RNAi (MFSR), including reduced climbing speed and climbing endurance, reduced fractional shortening of the heart, damaged myofibrils, and reduced mitochondria in HM. Besides, a HFD and MFSR increased triglyceride level and malondialdehyde level, decreased the Sirt1 and FOXO protein level, and reduced carnitine palmityl transferase I, superoxide dismutase, and catalase activity level, and they dow-regulated FOXO and bmm expression level in SM and HM. On the contrary, both muscle FOXO-specific overexpression (MFSO) and EE prevented abnormal changes of SM and HM in function, structure, or physiology caused by HFD and MFSR. Besides, EE also prevented defects of SM and HM induced by MFSR. CONCLUSIONS: Current findings confirmed MFSO and EE protected SM and heart from defects caused by a HFD via enhancing FOXO-realated antioxidant pathways and lipid catabolism. FOXO played a vital role in regulating HFD-induced defects in SM and HM, but FOXO was not a key regulatory gene of EE against damages in SM and HM. The mechanism was related to activity of Sirt1/FOXO/SOD (superoxide dismutase), CAT (catalase) pathways and lipid catabolism in SM and HM.

Activation of cardiac Nmnat/NAD+/SIR2 pathways mediates endurance exercise resistance to lipotoxic cardiomyopathy in aging Drosophila.

Endurance exercise is an important way to resist and treat high-fat diet (HFD)-induced lipotoxic cardiomyopathy, but the underlying molecular mechanisms are poorly understood. Here, we used Drosophila to identify whether cardiac Nmnat/NAD+/SIR2 pathway activation mediates endurance exercise-induced resistance to lipotoxic cardiomyopathy. The results showed that endurance exercise activated the cardiac Nmnat/NAD+/SIR2/FOXO pathway and the Nmnat/NAD+/SIR2/PGC-1α pathway, including up-regulating cardiac Nmnat, SIR2, FOXO and PGC-1α expression, superoxide dismutase (SOD) activity and NAD+ levels, and it prevented HFD-induced or cardiac Nmnat knockdown-induced cardiac lipid accumulation, malondialdehyde (MDA) content and fibrillation increase, and fractional shortening decrease. Cardiac Nmnat overexpression also activated heart Nmnat/NAD+/SIR2 pathways and resisted HFD-induced cardiac malfunction, but it could not protect against HFD-induced lifespan reduction and locomotor impairment. Exercise improved lifespan and mobility in cardiac Nmnat knockdown flies. Therefore, the current results confirm that cardiac Nmnat/NAD+/SIR2 pathways are important antagonists of HFD-induced lipotoxic cardiomyopathy. Cardiac Nmnat/NAD+/SIR2 pathway activation is an important underlying molecular mechanism by which endurance exercise and cardiac Nmnat overexpression give protection against lipotoxic cardiomyopathy in Drosophila.

Physical exercise prevents age-related heart dysfunction induced by high-salt intake and heart salt-specific overexpression in Drosophila.

A long-term high-salt intake (HSI) seems to accelerate cardiac aging and age-related diseases, but the molecular mechanism is still not entirely clear. Exercise is an effective way to delay cardiac aging. However, it remains unclear whether long-term exercise (LTE) can protect heart from aging induced by high-salt stress. In this study, heart CG2196(salt) specific overexpression (HSSO) and RNAi (HSSR) was constructed by using the UAS/hand-Gal4 system in Drosophila. Flies were given exercise and a high-salt diet intervention from 1 to 5 weeks of age. Results showed that HSSR and LTE remarkably prevented heart from accelerated age-related defects caused by HSI and HSSO, and these defects included a marked increase in heart period, arrhythmia index, malondialdehyde (MDA) level, salt expression, and dTOR expression, and a marked decrease in fractional shortening, SOD activity level, dFOXO expression, PGC-1α expression, and the number of mitochondria and myofibrils. The combination of HSSR and LTE could better protect the aging heart from the damage of HSI. Therefore, current evidences suggested that LTE resisted HSI-induced heart presenility via blocking CG2196(salt)/TOR/oxidative stress and activating dFOXO/PGC-1α. LTE also reversed heart presenility induced by cardiac-salt overexpression via activating dFOXO/PGC-1α and blocking TOR/oxidative stress.

A warm-up performed with proper-weight sandbags on the leg improves the speed and RPE performance of 100 m sprint in collegiate male sprinters.

BACKGROUND: Muscle performance can be notably improved following a preloading maximal or near maximal stimulus due to the induction of postactivation potentiation, but the success of a preloading exercise in generating a postactivation potentiation response depends on the balance between fatigue and potentiation. However, the optimal warm-up strategy for sprint runners before a match may be not well established until now. METHODS: Fifteen well-trained male sprint runners performed four different warm-up protocols: warm-up with 0% body mass; warm-up with 2% body mass; warm-up with 4% body mass; warm-up with 8% body mass. The weight-bearing sandbag was tied about 3~5 cm above each ankle joint. During the 100-meter test, the time and rating of perceived exertion (RPE) in the first 30 meters, time in the first 60 meters, and time in the 100 meters were recorded, respectively. Two-high-speed digital video cameras were separately set in the sagittal planes on the left side of a line drawn at a distance of 30 m and 60 m from the start line to record the sprint motion. RESULTS: A warm-up performed with a sandbag weighted 4% of body mass could significantly improve the time and the RPE score of 100 m sprint by improving average velocity, stride frequency, average stride length, and average accelerated velocity during the sections of 0~30 m, 30~60 m and 60~100 m. This positive effect was better than that of 2% body-weigh effect. However, a warm-up performed with a sandbag weighted 8% of body mass had no significant influence on the performance of a 100 m sprint. CONCLUSIONS: Current results indicated that a warm-up performed with proper-weight(4% body mass) sandbags on the leg was beneficial to the improvement of 100 m sprint performance, and the mechanism might be that it effectively activated the main muscles and neuromuscular regulation of running and produced a better postactivation potentiation.

Endurance exercise protects aging Drosophila from high-salt diet (HSD)-induced climbing capacity decline and lifespan decrease by enhancing antioxidant capacity.

A high-salt diet (HSD) is a major cause of many chronic and age-related defects such as myocardial hypertrophy, locomotor impairment and mortality. Exercise training can efficiently prevent and treat many chronic and age-related diseases. However, it remains unclear whether endurance exercise can resist HSD-induced impairment of climbing capacity and longevity in aging individuals. In our study, flies were given exercise training and fed a HSD from 1-week old to 5-weeks old. Overexpression or knockdown of salt and dFOXO were built by UAS/Gal4 system. The results showed that a HSD, salt gene overexpression and dFOXO knockdown significantly reduced climbing endurance, climbing index, survival, dFOXO expression and SOD activity level, and increased malondialdehyde level in aging flies. Inversely, in a HSD aging flies, endurance exercise and dFOXO overexpression significantly increased their climbing ability, lifespan and antioxidant capacity, but they did not significantly change the salt gene expression. Overall, current results indicated that a HSD accelerated the age-related decline of climbing capacity and mortality via upregulating salt expression and inhibiting the dFOXO/SOD pathway. Increased dFOXO/SOD pathway activity played a key role in mediating endurance exercise resistance to the low salt tolerance-induced impairment of climbing capacity and longevity in aging DrosophilaThis article has an associated First Person interview with the first author of the paper.

Synthesis of nanoparticle-assembled Zn3(VO4)2 porous networks via a facile coprecipitation method for high-rate and long-life lithium-ion storage.

A simple coprecipitation route followed by a calcination process was developed to prepare 2D hierarchical Zn3(VO4)2 porous networks formed by the crosslinkage of monolayered nanoparticles. As a promising anode for lithium ion batteries, the electrochemical performance of Zn3(VO4)2 was investigated. At a current density of 1.0 A g-1, the Zn3(VO4)2 porous networks could register a high reversible discharge capacity of 773 mA h g-1 and the capacity retention was 94% after 700 cycles. Moreover, a remarkable reversible discharge capacity of 445 mA h g-1 was achieved at a current density of 5 A g-1 after 1200 cycles. Even at a higher current density of 10.0 A g-1, a high reversible capacity of 527 mA h g-1 could be delivered, which still remained at 163 mA h g-1 after 1200 cycles. This superior performance is attributed to the unique 2D porous networks with a stable structure. This work shows a new avenue for facile, cheap, green, and mass production of zinc vanadate oxides with 2D porous hierarchical networks for next-generation energy conversion and storage devices.

Endurance exercise resistance to lipotoxic cardiomyopathy is associated with cardiac NAD+/dSIR2/PGC-1α pathway activation in old Drosophila.

Lipotoxic cardiomyopathy is caused by excessive lipid accumulation in myocardial cells and it is a form of cardiac dysfunction. Cardiac PGC-1α overexpression prevents lipotoxic cardiomyopathy induced by a high-fat diet (HFD). The level of NAD+ and Sir2 expression upregulate the transcriptional activity of PGC-1α. Exercise improves cardiac NAD+ level and PGC-1α activity. However, the relationship between exercise, NAD+/dSIR2/PGC-1α pathway and lipotoxic cardiomyopathy remains unknown. In this study, flies were fed a HFD and exercised. The heart dSir2 gene was specifically expressed or knocked down by UAS/hand-Gal4 system. The results showed that either a HFD or dSir2 knockdown remarkably increased cardiac TG level and d FAS expression, reduced heart fractional shortening and diastolic diameter, increased arrhythmia index, and decreased heart NAD+ level, dSIR2 protein, dSir2 and PGC-1α expression levels. Contrarily, either exercise or dSir2 overexpression remarkably reduced heart TG level, dFAS expression and arrhythmia index, and notably increased heart fractional shortening, diastolic diameter, NAD+ level, dSIR2 level, and heart dSir2 and PGC-1α expression. Therefore, we declared that exercise training could improve lipotoxic cardiomyopathy induced by a HFD or cardiac dSir2 knockdown in old Drosophila The NAD+/dSIR2/PGC-1α pathway activation was an important molecular mechanism of exercise resistance against lipotoxic cardiomyopathy.

The activation of cardiac dSir2-related pathways mediates physical exercise resistance to heart aging in old Drosophila.

Cardiac aging is majorly characterized by increased diastolic dysfunction, lipid accumulation, oxidative stress, and contractility debility. The Sir2/Sirt1 gene overexpression delays cell aging and reduces obesity and oxidative stress. Exercise improves heart function and delays heart aging. However, it remains unclear whether exercise delaying heart aging is related to cardiac Sir2/Sirt1-related pathways. In this study, cardiac dSir2 overexpression or knockdown was regulated using the UAS/hand-Gal4 system in Drosophila. Flies underwent exercise interventions from 4 weeks to 5 weeks old. Results showed that either cardiac dSir2 overexpression or exercise remarkably increased the cardiac period, systolic interval, diastolic interval, fractional shortening, SOD activity, dSIR2 protein, Foxo, dSir2, Nmnat, and bmm expression levels in the aging flies; they also notably reduced the cardiac triacylglycerol level, malonaldehyde level, and the diastolic dysfunction index. Either cardiac dSir2 knockdown or aging had almost opposite effects on the heart as those of cardiac dSir2 overexpression. Therefore, we claim that cardiac dSir2 overexpression or knockdown delayed or promoted heart aging by reducing or increasing age-related oxidative stress, lipid accumulation, diastolic dysfunction, and contractility debility. The activation of cardiac dSir2/Foxo/SOD and dSir2/Foxo/bmm pathways may be two important molecular mechanisms through which exercise works against heart aging in Drosophila.

Transcriptional Activator GmrA, Encoded in Genomic Island OI-29, Controls the Motility of Enterohemorrhagic Escherichia coli O157:H7.

Enterohemorrhagic Escherichia coli O157:H7 is a major human enteric pathogen capable of causing large outbreaks of severe infections that induce bloody diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome. Its genome contains 177 unique O islands (OIs) including those carrying the main virulence elements, Shiga toxin-converting phages (OI-45 and OI-93) and locus for enterocyte effacement (OI-148). However, many of these islands harbor only genes of unknown function. Here, we demonstrate that OI-29 encodes a newly discovered transcriptional activator, Z0639 (named GmrA), that is required for motility and flagellar synthesis in O157:H7. GmrA directly binds to the promoter of fliA, an RNA polymerase sigma factor, and thereby regulates flagellar genes controlled by FliA. Expression of gmrA is maximal under host conditions (37°C, neutral pH, and physiological osmolarity), and in the presence of host epithelial cells, indicative of a role of this gene in infection by promoting motility. Finally, GmrA was found to be a widespread regulator of bacterial motility and flagellar synthesis in different pathotypes of E. coli. Our work largely enriches our understanding of bacterial motility control, and provides another example of regulators acquired laterally that mediate flagellar synthesis.

Structure and genetics of a glycerol 2-phosphate-containing O-specific polysaccharide of Escherichia coli O33.

An O-specific polysaccharide was isolated by mild acid degradation of the lipopolysaccharide of Escherichia coli O33 followed by gel-permeation chromatography on Sephadex G-50. The polysaccharide was found to contain glycerol 2-phosphate (Gro-2-P), and the following structure of its tetrasaccharide repeat was established by sugar analysis, dephosphorylation, and 1D and 2D 1H and 13C NMR spectroscopy: The O33-antigen gene cluster was analyzed and found to be essentially consistent with the O-polysaccharide structure.

Endurance exercise prevents high-fat-diet induced heart and mobility premature aging and dsir2 expression decline in aging Drosophila.

High-Fat-Diet (HFD)-induced obesity is a major contributor to heart and mobility premature aging and mortality in both Drosophila and humans. The dSir2 genes are closely related to aging, but there are few directed reports showing that whether HFD could inhibit the expression dSir2 genes. Endurance exercise can prevent fat accumulation and reverse HFD-induced cardiac dysfunction. Endurance also delays age-relate functional decline. It is unclear whether lifetime endurance exercise can combat lifetime HFD-induced heart and mobility premature aging, and relieve the harmful HFD-induced influence on the dSir2 gene and lifespan yet. In this study, flies are fed a HFD and trained from when they are 1 week old until they are 5 weeks old. Then, triacylglycerol levels, climbing index, cardiac function, lifespan, and dSir2 mRNA expressions are measured. We show that endurance exercise improves climbing capacity, cardiac contraction, and dSir2 expression, and it reduces body and heart triacylglycerol levels, heart fibrillation, and mortality in both HFD and aging flies. So, lifelong endurance exercise delays HFD-induced accelerated age-related locomotor impairment, cardiac dysfunction, death, and dSir2 expression decline, and prevents HFD-induced premature aging in Drosophila.

WITHDRAWN: Regular exercise protects aging Drosophila from high-fat-diet-induced locomotor impairment, cardiac dysfunction, lifespan shortening, and Nmnat and dSir2 expression decline.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.