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Abstract We assessed the effect of GBT1118, a sickle hemoglobin polymerization inhibitor on bone loss in humanized sickle cell disease (SCD) mice. Healthy control (Ctrl) 4-months-old female and male mice were fed Vehicle-chow for 2-months, while SCD mice were fed Vehicle-chow or GBT1118-chow. By micro-CT, GBT1118 significantly increased femur metaphyseal trabecular thickness (Tb.Th) and tissue mineral density (TMD), and significantly decreased trabecular spacing in female SCD mice. In SCD male mice, there was significant reduction in epiphyseal trabecular bone volume fraction (BV/TV), Tb.Th and TMD and GBT1118 significantly increased BV/TV and TMD but not Tb.Th. A significant decrease in cortical area fraction in SCD female mice was rescued by GBT1118 but not SCD males. Markedly decreased mineralized femur trabeculae in SCD females and males was partially rescued by GBT1118. Bone histomorphometry of femurs demonstrated significantly decreased bone formation parameters and increased bone resorption parameters in SCD mice of both sex that were rescued by GBT1118. Significant alteration in bone and hypoxia related genes of SCD mice of both sexes were differentially modulated by GBT1118. We conclude that "a sickle hemoglobin polymerization inhibitor" might be efficacious in improving some parameters of SCD bone loss.

BackgroundMild cognitive impairment (MCI) is commonly defined as a transitional subclinical state between normal aging and dementia. A growing body of research indicates that health behaviors may play a protective role against cognitive decline and could potentially slow down the progression from MCI to dementia. The aim of this study is to conduct a bibliometric analysis of literature focusing on health behaviors and MCI to summarize the factors and evidence regarding the influence of health behaviors on MCI.MethodsThe study performed a bibliometric analysis by retrieving publications from the Science Citation Index and Social Sciences Citation Index sub-databases within the Web of Science Core Collection. Utilizing VOSviewer and CiteSpace software, a total of 2,843 eligible articles underwent co-citation, co-keywords, and clustering analyses. This methodology aimed to investigate the current status, trends, major research questions, and potential future directions within the research domain.ResultsThe bibliometric analysis indicates that research on healthy behaviors in individuals with MCI originated in 2002 and experienced rapid growth in 2014, reflecting the increasing global interest in this area. The United States emerged as the primary contributor, accounting for more than one-third of the total scientific output with 982 articles. Journals that published the most articles on MCI-related health behaviors included “Journal of Alzheimer’s Disease,” “Neurobiology of Aging,” “Frontiers in Aging Neuroscience,” and other geriatrics-related journals. High-impact papers identified by VOSviewer predominantly cover concepts related to MCI, such as diagnostic criteria, assessment, and multifactorial interventions. Co-occurrence keyword analysis highlights five research hotspots in health behavior associated with MCI: exercise, diet, risk factors and preventive measures for dementia, cognitive decline-related biomarkers, and clinical trials.ConclusionThis study provides a comprehensive review of literature on health behavior in individuals with MCI, emphasizing influential documents and journals. It outlines research trends and key focal points, offering valuable insights for researchers to comprehend significant contributions and steer future studies.

To meet the practical demand of wearable/portable electronics, developing high-efficiency and durable multifunctional catalyst and in-situ assembling catalysts into electrodes with flexible features are urgently needed but challenging. Herein, we report a simple route to fabricate bendable multifunctional electrodes by in-situ carbonization of metal ion absorbed polyaniline precursor. Alloy nanoparticles encapsulated in graphite layer are uniformly distributed in the N-doping carbon nanorod skeleton. Profiting from the favorable free-standing structure and the cooperative effect of metallic nanoparticles, graphitic layer and N doped-carbon architecture, the trifunctional electrodes exhibit prominent activities and stability toward HER, OER and ORR. Notably, due to the protection of carbon layer, the electrocatalysts show the reversible catalytic HER/OER properties. The overall water splitting device can continuously work for 12 h under frequent exchanges of cathode and anode. Importantly, the bendable metal air batteries fabricated by self-supported electrode not only displays the outstanding battery performance, achieving a decent peak power density (125 mW cm−2) and exhibiting favorable charge-discharge durability of 22 h, but also holds superb flexible stability. Specially, a lightweight self-driven water splitting unit is demonstrated with stable hydrogen production.

Abstract Bone loss is common in sickle cell disease (SCD), but the molecular mechanisms is unclear. Serum insulin-like growth factor 1 (IGF1) was low in SCD subjects and SCD mice. To determine if decreased IGF1 associated with low bone mass in SCD is due to reduced SCFA production by gut microbiota, we performed reciprocal fecal microbiota transplantation (FMT) between healthy control (Ctrl) and SCD mice. uCT and histomorphometry analysis of femur showed decreased bone volume/total volume (BV/TV), trabecular number (Tb.N), osteoblast surface/bone surface (Ob.S/BS), mineralizing surface/ bone surface (MS/BS), inter-label thickness (Ir.L.Th) in SCD mice were significantly improved after receiving Ctrl feces. Bone formation genes Alp, Col1, Runx2, and Dmp1 from SCD mice were significantly decreased and were rescued after FMT from Ctrl feces. Transplantation of Ctrl feces increased the butyrate, valerate, and propionate levels in cecal content of SCD mice. Decreased G-coupled protein receptors 41 and 43 (GPR41 and GPR43) mRNA in tibia and lower IGF1 in bone and serum of SCD mice were partially restored after FMT from Ctrl feces. These data indicate that the healthy gut microbiota of Ctrl mice is protective for SCD bone loss through regulating IGF1 in response to impaired bacterial metabolites SCFAs.

Abstract We have used Basic Fibroblast Growth Factor (FGF2) transgenic mice as experimental models for human X-linked hypophosphatemia (XLH)-related degenerative osteoarthritis (OA) to investigate the pathogenesis of the disease and to test potential pharmacotherapies for treatment. This study tested the efficacy of BJG398, a small molecule fibroblast growth factor receptor tyrosine kinase (FGFRTK) inhibitor, to rescue the knee joint osteoarthritis phenotype in High Molecular Weight fibroblast growth factor 2 transgenic (HMWTgFGF2) mice. BJG398 was administered in vivo to 8-month-old female HMWTgFGF2 mice for six weeks. Histomorphometry, immunohistochemistry and micro-CT were used to examine the knee joints in BGJ398-treated and control mice. We assessed: Fibroblast Growth Factor 23 (FGF23) expression and FGFR1 activity; Matrix metalloproteinase 13 (MMP13) and Aggrecanase2 (ADAMTS5) expression; then signaling by SMAD1/5/8-pSMAD6, pERK1/2 and Runt-related transcription factor 2 (RUNX2). Using PrimePCR arrays, we identified a contributing role for major target genes in the TGFB/BMP2 signaling pathway that were regulated by BGJ398. BGJ398 inhibited HMWFGF2/FGF23-induced increase in bone morphogenic protein receptor-1, bone morphogenic protein-2 and 4 and Serine peptidase inhibitor, clade E, member 1. The results from Micro-CT and histology show BGJ398 treatment rescued the OA changes in subchondral bone and knee articular cartilage of HMWTgFGF2 mice. The gene expression and signal transduction results provide convincing evidence that HMWFGF2 generates OA through FGFRTK with characteristic downstream signaling that defines OA, namely: increased FGF23-FGFR1 activity with BMP-BMPR, activation of pSMAD1/5/8-RUNX2 and pERK signaling pathways, then upregulation of MMP13 and ADAMTS5 to degrade matrix. BGJ398 treatment effectively reversed these OA molecular phenotypes, providing further evidence that the OA generated by HMWFGF2 in the transgenic mice is FGFR-mediated and phenocopies the OA found in the Hyp mouse homolog of XLH with a spontaneous mutation in the Phex (phosphate regulating endopeptidase on the X chromosome) gene and human XLH-OA. Overall, the results obtained here explain how the pleotropic effects of FGF2 emanate from the different functions of HMW protein isoforms for cartilage and bone homeostasis, and the pathogenesis of XLH-degenerative osteoarthropathy. BGJ398 inhibits HMWFGF2-induced osteoarthritis via multiple mechanisms. These results provided important scientific evidence for the potential application of BGJ398 as a therapeutic agent for osteoarthritis in XLH.

Ethanol abuse is a major public issue globally and withdrawal of ethanol after chronic exposure contributes to the development of behavioural changes. The present study evaluates vanillin effect against the ethanol withdrawal syndrome (EWS) and the associated anxiety. Rats were exposed to ethanol for 21 days at 7.2% concentration maximum with drinking water in a modified liquid diet. Vanillin at doses of 100 and 200 mg/kg were administered 30 min prior to ethanol withdrawal, and behavioural changes were observed at 1st, 2nd, 4th, 6th and 12th h of ethanol withdrawal. Moreover, the locomotor activity was assessed using the astrophotometer and level of anxiety by the elevated plus maze. The level of neurotransmitters and mRNA expression of corticotropin-releasing factor (CRF) and corticotropin releasing factor receptor 1 (CRFR1) were estimated in brain tissue of vanillin treated EWS rats. There was a significant improvement in the ethanol withdrawal behaviour in the vanillin treated group compared to EWS rats. The locomotor activity and level of anxiety was observed to be reduced significantly (p < 0.01) in the vanillin treated group compared to EWS rats. Treatment with vanillin ameliorates the altered level of g-aminobutyric acid (GABA), dopamine and glutamate and level of corticosterone in ethanol withdrawal rats. mRNA expression of CRF and CRFR1 was reduced significantly (p < 0.01) in brain tissue of the vanillin treated group compared to the EWS group of rats. In conclusion, data reveal that treatment with vanillin shows a beneficial effect against EWS and ethanol withdrawal associated anxiety by regulating CRF/CRFR1 expression.

Direct-seeded rice (Oryza sativa) (DSR) is gaining increasing acceptance worldwide because it saves both time and labor. A covering treatment is a simple method to improve early plant growth under direct-seeding conditions. Herein, field experiments were conducted to study the effects of different powdered organic covering materials, i.e., organic fertilizer, seedling substrate, nutrient soil A, and nutrient soil B. In addition, the effects of different covering thicknesses were studied, including 5, 10, 15, and 20 mm, on the germination and early growth of DSR varieties. The two rice varieties Wufengyou 286 and Zhongjiazao 17 were used for this study. The seedling substrate at 15 mm and nutrient soil A at 5 mm covering thickness significantly increased the rate of germination of Wufengyou 286 by 43.93% and 40.26%, respectively, compared to the control treatment. Organic fertilizer, seedling substrate, and nutrient soil A at covering thicknesses of 5 mm significantly increased the germination rate by 42.57%, 38.62%, and 40.10%, respectively, compared to the control. Notably, all the treatments increased the emergence rate, with Wufengyou 286 exhibiting the most pronounced effect. The seedling substrate at 10 mm covering thickness significantly increased the rate of emergence of Wufengyou286 by 15.42% compared to the control. Similarly, the seedling substrate at 10 mm covering thickness gave the best results by increasing the rate of emergence of Zhongjiazao 17 by 10.85% compared to the control. On average, the rate of emergence of Wufengyou 286 and Zhongjiazao 17 under the experimental treatment increased by 11.81% and 6.45%, respectively, compared to the control. The appropriate cover treatment enhanced the early growth of DSR by improving its morphological attributes, such as plant height and dry weight, and regulating the physio-biochemical responses, such as the production of antioxidants and photosynthetic pigments. The seedling growth rate of both varieties decreased as the thickness increased. This study elucidated the effects of different covering materials on the early growth of DSR, which can further guide their actual production.

Abstract Background Acute kidney injury (AKI) is a frequent and serious complication in patients with primary nephrotic syndrome (PNS). We aimed to evaluate the influencing factors of AKI in patients with PNS, to provide implications for the clinical management and nursing care of patients with PNS. Methods PNS patients who were treated in the Department of Nephrology in our hospital from January 1, 2020 to July 31, 2021 were included. The clinical characteristics and pathological type of PNS patients were evaluated. Pearson correlation and Logistic regression analysis were performed to analyze the related risk factors of AKI in patients with PNS. Results A total of 328 patients with PNS were included, the incidence of AKI in PNS patients was 28.05%. Pearson correlation analysis showed that diabetes(r = 0.688), pulmonary infection (r = 0.614), albumin (r = 0.779), serum creatinine (r = 0.617), uric acid (r = 0.522), blood urea nitrogen (r = 0.616), renal tubular casts (r = 0.707) were correlated with AKI in PNS patients (all P

As a highly productive rice, ratoon rice is widely planted worldwide, but the rolling of rice stubble in mechanical harvesting severely limits its total yield; based on this, some scholars have proposed rolled rice stubble righting machines. However, limited by the uncertainty of the field environment, the machine’s localization accuracy of the target needs to be improved. To address this problem, real-time detection of rolled rice stubble rows is a prerequisite. Therefore, this paper introduces a deep learning method for the first time to achieve this. To this end, we presented a novel approach to improve a model that is used for the simplification of Mask R-CNN, which does not require any modules to be added or replaced on the original model. Firstly, two branches in the second stage were deleted, and the region proposals output from the stage was used directly as the mask generation region, and segmentation performance was substantially improved after a simple optimization of the region proposals. Further, the contribution of the feature map was counted, and the backbone network was simplified accordingly. The resulting SMR-RS model was still able to perform instance segmentation and has better segmentation performance than Mask R-CNN and other state-of-the-art models while significantly reducing the average image processing time and hardware consumption.

Abstract Acid mine drainage (AMD) has caused serious and long-lasting damage to the environment in many countries. Preventing AMD formation at the source is considered the most direct and effective method of remediation. Carbide slag, an industrial waste, is a potential AMD treatment material due to its strong alkalinity. However, applying carbide slag at the source carries difficulties due to its rapid release of alkalinity. This is the first attempt to mix carbide slag with bentonite to prepare sustained-alkalinity-release particles for source control of AMD. The size of Ca(OH)2 crystallites is decreased from 267 to 211 nm, and the reduced part forms calcium silicate hydrate gel (C–S–H) between the carbide slag and bentonite. C–S–H encapsulated on the surface of the carbide slag, increasing the mechanical strength of the particles, and achieving slow release of alkalinity. The suggested optimum preparation conditions for the particles are as follows: bentonite-to-carbide slag mass ratio of 3:7, Na2CO3 dose of 10 wt%, and calcination temperature of 500 °C for 1 h. The particles can remove 105 mg/g Cu2+ within 12 h, and the loss rate is only 7.4%. The alkalinity release time of the particles is 4 times greater than that of carbide slag.

Metal/oxide interface is of fundamental significance to heterogeneous catalysis. Here, the authors construct a nanometer Pd/Bi2O3 interface by grafting Pd clusters onto Bi2O3 clusters and demonstrate its essential roles in the low-temperature semi-hydrogenation of acetylene.

Surface modification has been one of most effective methods to improve the electrochemical performance of lithium rich layered oxides. In this paper, the Li1.2Mn0.56Ni0.16Co0.08O2 microspheres are prepared by urea assisted combustion route, and then coated with proper amount of CaF2. XRD and SEM results show surface modification has not changed the structure of Li1.2Mn0.56Ni0.16Co0.08O2, and a uniform coating layer can be obtained. As lithium ion battery cathode, the optimal CaF2 (i.e, 2wt%) coated sample presents a high initial discharge capacity of 223 mAh·g-1 with Coulombic efficiency of 80.5% at 0.1C, which is much better than that of pristine sample. Also, a high discharge capacity of 119 mAh·g-1 can be obtained for CaF2 coated sample at 5C. The improved electrochemical performance may be attributed the formation of fast Li ion conductor on the surface supported by EIS study.

Morphing wings with the ability of shape changing may enlarge the flight envelop of air vehicles. This is particularly important for small-scale aircrafts demanding maneuverability and adaptability in dynamic environments. However, to design a shape-changing mechanism suitable for small drones is very challenging due to extreme requirements raised by dimensional constraint, actuating limits, and weight restriction in Micro Air Vehicles (MAVs). A novel design method of morphing wings is proposed for small-scale aircrafts in this paper. The morphing wing is composed of a heterogeneous architecture, including three components: a longitudinal spar with pneumatic actuators, chordwise stiffening ribs with cable-driven metastructures, and a compliant skin. Through employing both pneumatic networks with hyperelastic behavior and modified pantographic metastructures with tunable stiffness, structural deformation along both spanwise and chordwise. Mechanical behaviors of this morphing wing were investigated thoroughly by theorical analysis, numerical verification, and experimental validation. Theorical predictions agree well with the results of 3D Finite Element Method (FEM). With optimal design determined through design of experiment (DOE) and FEM, prototyped morphing wings were fabricated accordingly. The aerodynamic performance was examined by a wind tunnel test with a Particle Image Velocimetry (PIV) instrument. Results demonstrate the efficiency and capacity of this morphing wing to adjust aerodynamic layout of aircraft in a low-speed airflow environment. This proposed design provides a promising solution applicable to small-scale aircrafts with morphing wings.

Zeolites have attracted attention and have been applied as haemostatic agents; however, there are issues associated with released zeolite powder. Here, the authors report on the growth of zeolites on cotton fibres with high stability and haemostatic ability.

Oxidative stress is a common phenomenon in aquaculture, which can be induced by nutritional or environmental factors. Generally, oxidative stress causes poor growth performance, metabolic dysregulation, and even the death of aquatic animals. To identify a nutritional intervention strategy, high-fat diet (HFD) feeding (Experiment I) and acute ammonia nitrogen challenge (Experiment II) tests were carried out. In Experiment I, HFD feeding significantly decreased the growth performance concomitantly with excessive fat deposition in the liver and abdomen. The addition of 4-PBA in the diet improved the excessive fat accumulation. The activities of antioxidative enzymes were suppressed, and the levels of lipid and protein peroxidation were increased, indicating that HFD feeding induced oxidative stress. The endoplasmic reticulum stress (ERs) related genes were downregulated in the HFD group. Under a transmission electron microscope (TEM), more swollen and dilated ER lumen could be observed. These results indicated that the HFD induced ERs activation. Although 4-PBA acted as a potent ERs inhibitor, as evidenced by the alleviated alterations of ERs molecules and the ER ultrastructure, the oxidative stress was also attenuated by 4-PBA. In Experiment II, dietary 4-PBA improved the tolerance to the acute ammonia nitrogen challenge, as lower mortality and serum aminotransferase activity was found. Further results showed that 4-PBA decreased the peroxidation content and attenuated ERs, thus confirming the correlation between oxidative stress and ERs. Our findings showed that dietary 4-PBA supplementation can attenuate oxidative stress induced by a HFD or acute ammonia challenge; the mechanism is related to its potent inhibition effect for ERs.

The mechanisms of the anabolic effect of parathyroid hormone (PTH) in bone are not fully defined. The bone anabolic effects of PTH require fibroblast growth factor 2 (FGF2) as well as Wnt signaling and FGF2 modulates Wnt signaling in osteoblasts. In vivo PTH administration differentially modulated Wnt signaling in bones of wild type (WT) and in mice that Fgf2 was knocked out (Fgf2KO). PTH increased Wnt10b mRNA and protein in WT but not in KO mice. Wnt antagonist SOST mRNA and protein was significantly higher in KO group. However, PTH decreased Sost mRNA significantly in WT as well as in Fgf2KO mice, but to a lesser extent in Fgf2KO. Dickhopf 2 (DKK2) is critical for osteoblast mineralization. PTH increased Dkk2 mRNA in WT mice but the response was impaired in Fgf2KO mice. PTH significantly increased Lrp5 mRNA and phosphorylation of Lrp6 in WT but the increase was markedly attenuated in Fgf2KO mice. PTH increased β-catenin expression and Wnt/β-catenin transcriptional activity significantly in WT but not in Fgf2KO mice. These data suggest that the impaired bone anabolic response to PTH in Fgf2KO mice is partially mediated by attenuated Wnt signaling. Keywords: PTH, FGF2, Wnt signaling, Bone

Bone loss is a common complication in individuals with sickle cell disease (SCD). The mechanism(s) of bone loss in SCD subjects has not been fully investigated, and there are no targeted therapies to prevent or treat compromised bone health in this population. Recent studies showed that depletion of gut microbiota with antibiotics significantly reduced the number of aged neutrophils, thereby dramatically improved the inflammation-related organ damages in SCD mice. Since neutrophils, abundantly present in bone marrow (BM), regulate bone cells, and BM neutrophils, induced by inflammatory cytokines, are associated with a low number of osteoblasts (OBs), we hypothesize that neutrophil aging in the BM of SCD mice impairs OB function. Flow cytometry analysis showed BM neutrophil aging was significantly increased in SCD mice that was reduced with antibiotic treatment. In vitro co-culture of calvarial OBs from control (Ctrl) mice with BM neutrophils from Ctrl or SCD mice showed that BM neutrophils from SCD mice inhibit OB function but was rescued when neutrophils were from antibiotic-treated SCD mice. In summary, there is an accumulation of aged neutrophils in BM from SCD mice that may contribute to impaired OB function, and antibiotic treatment is able to partially rescue impaired OB function by decreasing neutrophil aging in the BM of SCD mice. Keywords: Sickle cell disease, Bone marrow, Neutrophil aging, Osteoblasts, Antibiotics

Aldehyde dehydrogenase 2 (ALDH2) polymorphisms are related to both stroke risk and alcohol consumption. However, the influence of ALDH2 polymorphisms and alcohol consumption on cognitive impairment after ischemic stroke remains unknown, as do the possible mechanisms. We enrolled 180 Han Chinese ischemic stroke patients from four community health centers in Bengbu, China. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA), and two different MoCA cutoff scores were used to define cognitive impairment in ischemic stroke patients. The ALDH2 genotypes were determined using polymerase chain reaction and direct sequencing. To assess the associations of ALDH2 polymorphisms and alcohol consumption with cognitive impairment after ischemic stroke, we performed binary logistic regression analysis with odds ratios. We revealed that individuals with the ALDH2 wild-type genotype were more likely to have high MoCA scores than those with the mutant and heterozygous types (p=0.034). In addition, using two MoCA cutoff scores, the percentage of moderate to excessive alcohol consumption in the cognitive impairment group was higher than that in the nonimpairment group (p=0.001). The levels of 4-hydroxy-2-nonenal (p=0.001) and swallowing function (p=0.001) were also higher in the cognitive impairment group than in the nonimpairment group. Moreover, after adjusting for other potential risk factors, ALDH2 polymorphisms and alcohol consumption had a significant synergistic effect on cognitive impairment (p=0.022). Specifically, the ALDH2∗2 mutant allele and higher alcohol consumption were associated with cognitive impairment and swallowing ability after ischemic stroke. Targeting ALDH2 may be a useful biomarker for cognitive rehabilitation following ischemic stroke.

Selective oxidation of methane to methanol has been often considered as a “holy grail” reaction in catalysis. Herein, we systematically investigate the effect of solution pH and Pd-to-Au ratio of AuPdx colloid on the catalytic performance of methane oxidation. It is revealed that these two parameters can determine the amount of H2O2 participated in the reaction, which is linearly related to the productivity of oxygenates. A high catalytic performance in methane activation requires a high utilization of H2O2 to generate more ·OH. The optimal pH is 3.0 and the optimal Pd-to-Au ratio is between 0.1 to 0.7.

Summary: Cisplatin-based neoadjuvant chemotherapy has been shown to improve survival in patients with squamous cell carcinoma (SCC), but clinical biomarkers to predict chemosensitivity remain elusive. Here, we show the long noncoding RNA (lncRNA) LINC01011, which we termed cisplatin-sensitivity-associated lncRNA (CISAL), controls mitochondrial fission and cisplatin sensitivity by inhibiting BRCA1 transcription in tongue SCC (TSCC) models. Mechanistically, we found CISAL directly binds the BRCA1 promoter and forms an RNA-DNA triplex structure, sequestering BRCA1 transcription factor-GABPA away from the downstream regulatory binding region. Importantly, the clinical relevance of these findings is suggested by the significant association of CISAL and BRCA1 expression levels in TSCC tumors with neoadjuvant chemosensitivity and overall survival. We propose a new model where lncRNAs are tethered at gene promoter by RNA-DNA triplex formation, spatially sequestering transcription factors away from DNA-binding sites. Our study uncovers the potential of CISAL-BRCA1 signaling as a potential target to predict or improve chemosensitivity. : Biological Sciences; Molecular Biology; Cell Biology; Cancer Subject Areas: Biological Sciences, Molecular Biology, Cell Biology, Cancer

Tripterygium wilfordii Hook F. (TWHF) is a Chinese traditional medicine with cardiac toxicities. However, the mechanism of acute cardiac toxicity is not very clear. By using patch clamp techniques, we found that 0.05 mg/ml and 0.1 mg/ml of the aqueous crude extract of TWHF inhibit 21.4 ± 1.6% and 86.7 ± 5.7% (n = 5) of hERG current Amplitudes (IhERG) respectively. We further found that Celastrol, one of main components of TWHF, inhibits hERG with an IC50 of 0.83 μM. Additional mutagenesis studies show that mutations of T623A, S624A and F656A significantly alter the inhibition and S624A has the strongest effect, supported by our docking model. Our data suggest that inhibition of hERG channel activity by Celastrol contributed to TWHF cardiotoxicity.

Microbial-derived natural products are important in both the pharmaceutical industry and academic research. As the metabolic potential of original producer especially Streptomyces is often limited by slow growth rate, complicated cultivation profile, and unfeasible genetic manipulation, so exploring a Streptomyces as a super industrial chassis is valuable and urgent. Streptomyces sp. FR-008 is a fast-growing microorganism and can also produce a considerable amount of macrolide candicidin via modular polyketide synthase. In this study, we evaluated Streptomyces sp. FR-008 as a potential industrial-production chassis. First, PacBio sequencing and transcriptome analyses indicated that the Streptomyces sp. FR-008 genome size is 7.26 Mb, which represents one of the smallest of currently sequenced Streptomyces genomes. In addition, we simplified the conjugation procedure without heat-shock and pre-germination treatments but with high conjugation efficiency, suggesting it is inherently capable of accepting heterologous DNA. In addition, a series of promoters selected from literatures was assessed based on GusA activity in Streptomyces sp. FR-008. Compared with the common used promoter ermE*-p, the strength of these promoters comprise a library with a constitutive range of 60–860%, thus providing the useful regulatory elements for future genetic engineering purpose. In order to minimum the genome, we also target deleted three endogenous polyketide synthase (PKS) gene clusters to generate a mutant LQ3. LQ3 is thus an “updated” version of Streptomyces sp. FR-008, producing fewer secondary metabolites profiles than Streptomyces sp. FR-008. We believe this work could facilitate further development of Streptomyces sp. FR-008 for use in biotechnological applications.

In this paper, dynamic compression tests are developed to investigate the dynamic compression mechanical properties of the aluminum honeycomb structures at different strain rates, especially at the high strain rates. The difficulties at the high strain rates exist due to the large deformation, the low wave resistance and the size effect of the honeycomb structures. The Split Hopkinson Pressure Bar (SPHB) test method is carried out and special measures such as the adoption of waveform shaper, the size optimization of the impact bar and the specimen, and employment of the semiconductor strain gauge, etc. are taken to overcome the difficulties. It is discovered that the dynamic compression mechanical properties possess a stress hardening effect at a high strain rate from 1.3 × 103 s−1 to 2.0 × 103 s−1, but then a stress softening effect at a high strain rate of 4.6 × 103 s−1. It is also discovered that the yield strength and the average plateau stress at the strain rate of 2.0 × 103 s−1 is higher than that at the strain rate of 1.3 × 103 s−1. However, the yield strength and the average plateau stress at the strain rate of 4.6 × 103 s−1 is lower than that at the strain rate of 2.0 × 103 s−1 and 1.3 × 103 s−1, but higher than that at a quasi-static state. This indicates that the aluminum honeycomb structure is sensitive to the strain rate. Additionally, the damage mode of the aluminum honeycomb structure is plastic buckling, collapse and folding of the cell wall, which is carried out using dynamic compression tests. The folding length of the cell wall at a higher strain rate is found to be longer than that at a lower strain rate. The test results can also be used as the stress−strain curves of the honeycomb constitutive model at the high strain rates to carry out the numerical simulation of high-speed impact.

Quikclot has been used many years for treating external hemorrhage in the battle field. In this study, the hemostatic performance of NZG-JY (natural zeolite granules from Jinyun, China) was evaluated and compared with Quikclot in a lethal rabbit model of complex groin injury. Fifty-six anesthetized rabbits were randomized to three different groups: (1) NZG-JY (n = 19); (2) Quikclot (n = 19); and (3) medical gauze (n = 18). Survival was recorded three hours after the application of the hemostatic agents. The wound healing properties of the survived animals (n = 4 for each group) were observed a week later. The clotting efficiency is 100% for the animals in the NZG-JY and the Quikclot group, while only 5.6% in the gauze group. The mortality in the NZG-JY group (21.0%) is significantly less than that in the Quikclot group (52.6%) and the gauze group (66.7%). A good healing property was achieved in all animals that survived in the NZG-JY group, while three quarters of the animals in the Quikclot group had serious necrotic tissue. NZG-JY significantly decreases the mortality in a lethal rabbit model of complex groin injury and demonstrates good healing properties.

Background: To investigate the effect of using intrauterine devices (IUDs) during the fertile window on women′s reproductive system health. Materials and Methods: 2,744 postmenopausal women in the Minhang District, Shanghai, China were enrolled. In the IUDs group there were 2,253 women; in the tubal ligation group there were 202 women and there were 289 women in the control group. We selected subjects according to the cases number in different hospital by using step sampling, and, in addition, collected the sociological data and information of the previously used contraceptives by the subjects, which included whether the contraceptives were used appropriately and the effect they had. Kolmogorov-Smirnov test, Levene′s test, and logistic regression analysis were used to analyze the data. Results: The prevalence rate of benign reproductive system conditions was significantly different among them (P < 0.05). Further comparison revealed, the rate in Group 1 was significantly lower than that in Group 2 and Group 3 (P < 0.05, respectively). Results of logistic regression analysis show that the risk factors for development of such conditions lie in the women′s pregnancy history [odds ratio (OR) = 3.85], reproductive history (OR = 0.5), the use of IUD in fertile window (OR = 0.4), tubal ligation (OR = 1.74), birth control time (OR = 0.9), contraceptive failure history (OR = 1.7), and history of family planning procedures (OR = 1.73). Conclusion: IUDs, maybe, can effectively reduce the risk of getting benign reproductive conditions in postmenopausal females.