TRPV4 antagonist suppresses retinal ganglion cell apoptosis by regulating the activation of CaMKII and TNF-α expression in a chronic ocular hypertension rat model.

Glaucoma is characterized by a progressive loss of retinal ganglion cells (RGCs), leading to irreversible visual function impairment. Sustained increase in intraocular pressure represents a major risk factor for glaucoma, yet the underlying mechanisms of RGC apoptosis induced by intraocular pressure remains unclear. This study aims to investigate the role of TRPV4 in RGC apoptosis in a rat model of chronic ocular hypertension (COH) and the underlying molecular mechanism. In the COH rat models, we evaluated the visual function, retinal pathological changes and RGC apoptosis. TRPV4 expression and downstream signaling molecules were also detected. We found that RGC density decreased and RGC apoptosis was induced in COH eyes compared with control eyes. TRPV4 expression increased significantly in response to elevated IOP. TRPV4 inhibition by the TRPV4 antagonist HC-067047 (HC-067) suppressed RGC apoptosis and protected visual function. HC-067 treatment upregulated the phosphorylation of CaMKII in both control and COH eyes. Finally, HC-067 treatment suppressed the production of TNF-α induced by ocular hypertension. The TRPV4 antagonist HC-067 might suppress RGC apoptosis by regulating the activation of CaMKII and inhibiting the production of TNF-α in the COH model. This indicated that TRPV4 antagonists may be a potential and novel therapeutic strategy for glaucoma.

Integrative metagenomic and metabolomic analyses reveal the potential of gut microbiota to exacerbate acute pancreatitis.

Early dysbiosis in the gut microbiota may contribute to the severity of acute pancreatitis (AP), however, a comprehensive understanding of the gut microbiome, potential pathobionts, and host metabolome in individuals with AP remains elusive. Hence, we employed fecal whole-metagenome shotgun sequencing in 82 AP patients and 115 matched healthy controls, complemented by untargeted serum metabolome and lipidome profiling in a subset of participants. Analyses of the gut microbiome in AP patients revealed reduced diversity, disrupted microbial functions, and altered abundance of 77 species, influenced by both etiology and severity. AP-enriched species, mostly potential pathobionts, correlated positively with host liver function and serum lipid indicators. Conversely, many AP-depleted species were short-chain fatty acid producers. Gut microflora changes were accompanied by shifts in the serum metabolome and lipidome. Specifically, certain gut species, like enriched Bilophila wadsworthia and depleted Bifidobacterium spp., appeared to contribute to elevated triglyceride levels in biliary or hyperlipidemic AP patients. Through culturing and whole-genome sequencing of bacterial isolates, we identified virulence factors and clinically relevant antibiotic resistance in patient-derived strains, suggesting a predisposition to opportunistic infections. Finally, our study demonstrated that gavage of specific pathobionts could exacerbate pancreatitis in a caerulein-treated mouse model. In conclusion, our comprehensive analysis sheds light on the gut microbiome and serum metabolome in AP, elucidating the role of pathobionts in disease progression. These insights offer valuable perspectives for etiologic diagnosis, prevention, and intervention in AP and related conditions.

Control of metal-support interaction for tunable CO hydrogenation performance over Ru/TiO2 nanocatalysts.

The catalytic behavior of CO hydrogenation can be modulated by metal-support interactions, while the role of the support remains elusive. Herein, we demonstrate that the presence of strong metal-support interactions (SMSI) depends strongly on the crystal phase of TiO2 (rutile or anatase) and the treatment conditions for the TiO2 support, which could critically control the activity and selectivity of Ru-based nanocatalysts for CO hydrogenation. High CO conversion and olefin selectivity were observed for Ru/rutile-TiO2 (Ru/r-TiO2), while catalysts supported by anatase (a-TiO2) showed almost no activity. Characterization confirmed that the SMSI effect could be neglected for Ru/r-TiO2, while it is dominant on Ru/a-TiO2 after reduction at 300 °C, resulting in the coverage of Ru nanoparticles by TiOx overlayers. Such SMSI could be suppressed by H2 treatment of the a-TiO2 support and the catalytic activity of the as-obtained Ru/a-TiO2(H2) can be greatly elevated from almost inactive to >50% CO conversion with >60% olefin selectivity. Further results indicated that the surface reducibility of the TiO2 support determines the SMSI state and catalytic performance of Ru/TiO2 in the CO hydrogenation reaction. This work offers an effective strategy to design efficient catalysts for the FTO reaction by regulating the crystal phase of the support.

Prognostic Value of Immunohistochemistry-based Subtyping Before and After Neoadjuvant Chemotherapy in Patients with Triple-negative Breast Cancer.

To assess the predictive and prognostic value of a subtyping method based on immunohistochemistry in patients with triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC). This study included patients with TNBC treated with anthracycline- and taxane-based NAC and curative surgery. Immunohistochemical (IHC) subtyping was performed using core needle biopsy specimens before NAC (pre-NAC) and residual tumors after NAC (post-NAC). Logistic regression was performed to identify predictive biomarkers of pathological complete response (pCR). Invasive disease-free survival (iDFS), distant disease-free survival (DDFS), and overall survival (OS) were assessed using the log-rank test and Cox proportional hazards regression. A total of 230 patients were followed up for a median of 59 months. Clinical lymph node status and the pre-NAC subtype were independent predictors of pCR (P=0.006 and 0.005, respectively). The pre-NAC subtype was an independent prognostic factor for long-term survival (iDFS: P < 0.001, DDFS: P=0.010, and OS: P=0.044). Among patients with residual disease (RD) after NAC, approximately 45% of tumors changed their IHC subtype. Furthermore, the post-NAC subtype, but not the pre-NAC subtype, was strongly associated with the survival of patients with RD (iDFS: P < 0.001, DDFS: P=0.005, and OS: P=0.006). The IHC subtype predicted response to NAC and long-term survival in patients with early TNBC. In patients with RD, almost 45% of the tumors changed subtype after NAC. The IHC subtype should be considered when planning additional therapies pre- and post-NAC.

NLRP14 deficiency causes female infertility with oocyte maturation defects and early embryonic arrest by impairing cytoplasmic UHRF1 abundance.

Oocyte maturation is vital to attain full competence required for fertilization and embryogenesis. NLRP14 is preferentially expressed in mammalian oocytes and early embryos. Yet, the role and molecular mechanism of NLRP14 in oocyte maturation and early embryogenesis are poorly understood, and whether NLRP14 deficiency accounts for human infertility is unknown. Here, we found that maternal loss of Nlrp14 resulted in sterility with oocyte maturation defects and early embryonic arrest (EEA). Nlrp14 ablation compromised oocyte competence due to impaired cytoplasmic and nuclear maturation. Importantly, we revealed that NLRP14 maintained cytoplasmic UHRF1 abundance by protecting it from proteasome-dependent degradation and anchoring it from nuclear translocation in the oocyte. Furthermore, we identified compound heterozygous NLRP14 variants in women affected by infertility with EEA, which interrupted the NLRP14-UHRF1 interaction and decreased UHRF1 levels. Our data demonstrate NLRP14 as a cytoplasm-specific regulator of UHRF1 during oocyte maturation, providing insights into genetic diagnosis for female infertility.

Symbionts in Hodgkinia-free cicadas and their implications for co-evolution between endosymbionts and host insects.

IMPORTANCE: Obligate symbionts in sap-sucking hemipterans are harbored in either the same or different organs, which provide a unique perspective for uncovering complicated insect-microbe symbiosis. Here, we investigated the distribution of symbionts in adults of 10 Hodgkinia-free cicada species of 2 tribes (Sonatini and Polyneurini) and the co-phylogeny between 65 cicada species and related symbionts (Sulcia and YLSs). We revealed that YLSs commonly colonize the bacteriome sheath besides the fat bodies in these two tribes, which is different with that in most other Hodgkinia-free cicadas. Co-phylogeny analyses between cicadas and symbionts suggest that genetic variation of Sulcia occurred in Sonatini and some other cicada lineages and more independent replacement events in the loss of Hodgkinia/acquisition of YLS in Cicadidae. Our results provide new information on the complex relationships between auchenorrhynchans and related symbionts.

Homozygous missense variant in MEIOSIN causes premature ovarian insufficiency.

STUDY QUESTION: Are variants of genes involved in meiosis initiation responsible for premature ovarian insufficiency (POI)? SUMMARY ANSWER: A MEIOSIN variant participates in the pathogenesis of human POI by impairing meiosis due to insufficient transcriptional activation of essential meiotic genes. WHAT IS KNOWN ALREADY: Meiosis is the key event for the establishment of the ovarian reserve, and several gene defects impairing meiotic homologous recombination have been found to contribute to the pathogenesis of POI. Although STRA8 and MEIOISN variants have been found to associate with POI in a recent study, the condition of other meiosis initiation genes is unknown and direct evidence of variants participating in the pathogenesis of POI is still lacking. STUDY DESIGN, SIZE, DURATION: This was a retrospective genetic study. An in-house whole exome sequencing (WES) database of 1030 idiopathic POI patients was screened for variations of meiosis initiation genes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Homozygous or compound heterozygous variations of genes involved in meiosis initiation were screened in the in-house WES database. The pathogenicity of the variation was verified by in vitro experiments, including protein structure prediction and dual-luciferase reporter assay. The effect of the variant on ovarian function and meiosis was demonstrated through histological analyses in a point mutation mouse model. MAIN RESULTS AND THE ROLE OF CHANCE: One homozygous variant in MEIOSIN (c.1735C>T, p.R579W) and one in STRA8 (c.258 + 1G>A), which initiates meiosis via the retinoic acid-dependent pathway, were identified in a patient with idiopathic POI respectively. The STRA8 variation has been reported in the recently published work. For the MEIOSIN variation, the dual-luciferase reporter assay revealed that the variant adversely affected the transcriptional function of MEIOSIN in upregulating meiotic genes. Furthermore, knock-in mice with the homologous mutation confirmed that the variation impacted the meiotic prophase I program and accelerated oocyte depletion. Moreover, the variant p.R579W localizing in the high-mobility group (HMG) box domain disrupted the nuclear localization of the MEIOSIN protein but was dispensable for the cell-cycle switch of oocytes, suggesting a unique role of the MEIOSIN HMG box domain in meiosis initiation. LIMITATIONS, REASONS FOR CAUTION: Further studies are needed to explore the role of other meiosis initiation genes in the pathogenesis of POI. WIDER IMPLICATIONS OF THE FINDINGS: The MEIOSIN variant was verified to cause POI by impaired transcriptional regulation of meiotic genes and was inherited by a recessive mode. The function of HMG box domain in MEIOSIN protein was also expanded by this study. Although causative variations in meiotic initiation genes are rare in POI, our study confirmed the pathogenicity of a MEIOSIN variant and elucidated another mechanism of human infertility. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Key Research & Developmental Program of China (2022YFC2703800, 2022YFC2703000), National Natural Science Foundation for Distinguished Young Scholars (82125014), National Natural Science Foundation of China (32070847, 32170867, 82071609), Basic Science Center Program of NSFC (31988101), Natural Science Foundation of Shandong Province for Grand Basic Projects (ZR2021ZD33), Natural Science Foundation of Shandong Province for Excellent Young Scholars (ZR2022YQ69), Taishan Scholars Program for Young Experts of Shandong Province (tsqn202211371), and Qilu Young Scholars Program of Shandong University. The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Volatile fatty acids bio-production using extracellular polymeric substances disengaged from sludge for carbon source recycling.

Excessive waste-activated sludge (WAS) and insufficient carbon source (CS) for biological nitrogen removal (BNR) often coexist in municipal sewage treatment. Although the production of volatile fatty acids (VFAs) from WAS has been recognized as a promising solution, the development is limited by low VFAs production efficiency and dewatering deterioration of sludge. This study extracted the extracellular polymeric substances (EPS) from sludge by low-temperature thermal-hydrolysis (LTH) and high-speed hydro-cyclone (HSHC) pretreatment and recovered it for high-quality VFAs bio-production in thermophilic fermentation. Microbial mechanism analysis disclosed that interspecific interaction networks composed of functional flora, which accumulate VFAs by bio-converting EPS primarily and supplemented by EPS synthesis, guaranteed the efficient bio-production of VFAs. This process scheme shows promise in providing alternative denitrification CSs and avoiding deterioration of sludge dewaterability.

Dynamic Translational Landscape Revealed by Genome-Wide Ribosome Profiling under Drought and Heat Stress in Potato.

The yield and quality of potatoes, an important staple crop, are seriously threatened by high temperature and drought stress. In order to deal with this adverse environment, plants have evolved a series of response mechanisms. However, the molecular mechanism of potato's response to environmental changes at the translational level is still unclear. In this study, we performed transcriptome- and ribosome-profiling assays with potato seedlings growing under normal, drought, and high-temperature conditions to reveal the dynamic translational landscapes for the first time. The translational efficiency was significantly affected by drought and heat stress in potato. A relatively high correlation (0.88 and 0.82 for drought and heat stress, respectively) of the fold changes of gene expression was observed between the transcriptional level and translational level globally based on the ribosome-profiling and RNA-seq data. However, only 41.58% and 27.69% of the different expressed genes were shared by transcription and translation in drought and heat stress, respectively, suggesting that the transcription or translation process can be changed independently. In total, the translational efficiency of 151 (83 and 68 for drought and heat, respectively) genes was significantly changed. In addition, sequence features, including GC content, sequence length, and normalized minimal free energy, significantly affected the translational efficiencies of genes. In addition, 28,490 upstream open reading frames (uORFs) were detected on 6463 genes, with an average of 4.4 uORFs per gene and a median length of 100 bp. These uORFs significantly affected the translational efficiency of downstream major open reading frames (mORFs). These results provide new information and directions for analyzing the molecular regulatory network of potato seedlings in response to drought and heat stress.

Type 1 interferon signature in peripheral blood mononuclear cells and monocytes of idiopathic inflammatory myopathy patients with different myositis-specific autoantibodies.

Background: Myositis-specific autoantibodies (MSAs) are clinically used to diagnose and define idiopathic inflammatory myopathy (IIM) subsets. However, the underlying pathogenic mechanisms of patients with different MSAs remain unclear. Methods: A total of 158 Chinese patients with IIM and 167 gender- and age-matched healthy controls (HCs) were enrolled. Transcriptome sequencing (RNA-Seq) was performed with peripheral blood mononuclear cells (PBMCs), followed by the identification of differentially expressed genes (DEGs) and analysis of gene set enrichment analysis, immune cell infiltration, and WGCNA. Monocyte subsets and related cytokines/chemokines were quantified. The expressions of interferon (IFN)-related genes were validated using qRT-PCR and Western blot in both PBMCs and monocytes. We also performed correlation analysis and ROC analysis to explore the potential clinical significance of the IFN-related genes. Results: There were 1,364 genes altered in patients with IIM, including 952 upregulated and 412 downregulated genes. The type I interferon (IFN-I) pathway was remarkably activated in patients with IIM. Compared with patients with other MSAs, IFN-I signatures were significantly activated in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibodies. In total, 1,288 hub genes associated with IIM onset were identified using WGCNA, including 29 key DEGs associated with IFN signaling. The patients had more CD14brightCD16- classical, CD14brightCD16+ intermediate, and fewer CD14dimCD16+ non-classical monocyte subsets. Plasma cytokines like IL-6 and TNF and chemokines including CCL3 and MCPs increased. The validation of IFN-I-related gene expressions was consistent with the findings from RNA-Seq. The IFN-related genes were correlated with laboratory parameters and helpful for IIM diagnosis. Conclusion: Gene expressions were remarkably altered in the PBMCs of IIM patients. Anti-MDA5+ IIM patients had a more pronounced activated IFN signature than others. Monocytes exhibited a proinflammatory feature and contributed to the IFN signature of IIM patients.

Impact of body mass index in therapeutic response for HER2 positive breast cancer treated with neoadjuvant targeted therapy: a multi-center study and meta-analysis.

While overweight/obesity has become a major public health issue worldwide, any association between body mass index (BMI) and therapeutic response in neoadjuvant targeted therapy treated HER2 positive breast cancer patients remain unclear. The information from a total of four-hundred and ninety-one neoadjuvant targeted therapy treated HER2 positive breast cancer patients from four institutions were retrospectively collected. Univariate and multivariate logistic analysis was developed to determine the association between BMI and therapeutic response. A meta-analysis of published literature was then conducted to confirm the effect of overweight/obesity on pCR for patients treated with neoadjuvant targeted therapy. Restricted cubic spline (RCS) adjusted for confounding factors demonstrated a decrease pCR with increasing BMI (OR = 0.937, P = 0.045). Patients were then categorized into under/normal weight (n = 299) and overweight/obesity (n = 192). Overweight/obese patients were independently associated with a poor therapeutic response. In the subgroup analysis, a significant negative impact of overweight/obesity on pCR can be observed both in single-targeted (OR = 0.556; P = 0.02) and dual-targeted (OR = 0.392; P = 0.021) populations. Six eligible studies involving 984 neoadjuvant targeted therapy treated HER2 positive breast cancer patients were included in the meta-analysis. The meta-analysis also demonstrated that overweight/obesity was significantly associated with a poor response to neoadjuvant anti-HER2 therapy (OR = 0.68; P = 0.007). Our result show that overweight and obese HER2 positive breast cancer patients are less likely to achieve pCR after neoadjuvant targeted therapy.

Effects of alkaline biochar on nitrogen transformation with fertilizer in agricultural soil.

The loss and negative impacts of nitrogen from fertilized soils remain a global challenge in agricultural field. Ammonium nitrogen (NH4+-N) and nitrate nitrogen (NO3--N) leaching, together with volatile ammonia loss are the main pathways of nitrogen loss. To improve nitrogen availability, alkaline biochar with improved adsorption capacities is a promising soil amendment. This study was objected to investigate the effects of alkaline biochar (ABC, pH 8.68) on nitrogen mitigation, the effects on nitrogen loss, and the interactions among the mixed soils (biochar, nitrogen fertilizer, and soil) under both pot and field experiments. From pot experiments, ABC addition resulted in the poor reservation of NH4+-N which converted to volatile NH3 under higher alkaline environments, mainly occurring in the first 3 days. But after, NO3--N could be largely retained in surface soil by ABC addition. The reservation of NO3--N by ABC offsets the loss of volatile NH3, and ABC ultimately showed positive reservations of nitrogen with fertilization. In the field experiment, the addition of urea inhibitor (UI) addition could inhibit the volatile NH3 loss caused by ABC mainly in the first week. The long-term operation demonstrated that ABC supported persistent effectiveness in reducing N loss, while UI treatment temporarily delayed the N loss through inhibition of fertilizer hydrolysis. Therefore, the addition of both ABC and UI contributed to reserve soil N in layers (0-50 cm) suitable for crop growth thus improving crops growth.

High leukocyte mitochondrial DNA copy number contributes to poor prognosis in breast cancer patients.

BACKGROUND: Compelling evidence has indicated a significant association between leukocyte mitochondrial DNA copy number (mtDNAcn) and prognosis of several malignancies in a cancer-specific manner. However, whether leukocyte mtDNAcn can predict the clinical outcome of breast cancer (BC) patients has not been well investigated. METHODS: The mtDNA copy number of peripheral blood leukocytes from 661 BC patients was measured using a Multiplex AccuCopy™Kit based on a multiplex fluorescence competitive PCR principle. Kaplan-Meier curves and Cox proportional hazards regression model were applied to investigate the association of mtDNAcn with invasive disease-free survival (iDFS), distant disease-free survival (DDFS), breast cancer special survival (BCSS), and overall survival (OS) of patients. The possible mtDNAcn-environment interactions were also evaluated by the Cox proportional hazard regression models. RESULTS: BC patients with higher leukocyte mtDNA-CN exhibited a significantly worse iDFS than those with lower leukocyte mtDNAcn (5-year iDFS: fully-adjusted model: HR = 1.433[95%CI 1.038-1.978], P = 0.028). Interaction analyses showed that mtDNAcn was significantly associated with hormone receptor status (adjusted p for interaction: 5-year BCSS: 0.028, 5-year OS: 0.022), so further analysis was mainly in the HR subgroup. Multivariate Cox regression analysis demonstrated that mtDNAcn was an independent prognostic factor for both BCSS and OS in HR-positive patients (HR+: 5-year BCSS: adjusted HR (aHR) = 2.340[95% CI 1.163-4.708], P = 0.017 and 5-year OS: aHR = 2.446 [95% CI 1.218-4.913], P = 0.011). CONCLUSIONS: For the first time, our study demonstrated that leukocyte mtDNA copy number might influence the outcome of early-stage breast cancer patients depending on intrinsic tumor subtypes in Chinese women.

Improved lithium ion storage performance of Ti3C2Tx MXene@S composite with carboxymethyl cellulose binder.

MXenes are regarded as promising electrode materials for lithium-ion batteries owing to their high electrical conductivity and two-dimensional structure but suffer from low intrinsic specific capacities. In this study, we fabricate sulphur-doped multilayer Ti3C2Tx MXenes via calcination and annealing using sublimed sulphur as the sulphur source. After sulphur doping, the interlayer spacing of Ti3C2Tx increases, which is favourable for Li-ion insertion. The Ti3C2Tx MXene@S composite exhibits excellent electrochemical performance. A high reversible specific capacity of 393.8 mAh g-1 at a current density of 100 mA g-1 after 100 cycles is obtained. Additionally, a negative fading phenomenon is observed when the specific capacity increases to 858.9 mAh g-1 after 2550 cycles at 1 A g-1 and to 322.2 mA h g-1 after 3600 cycles at 5 A g-1 from the initial 267.3 mAh g-1. We systematically investigate the effects of two different binders (polyvinylidene difluoride and carboxymethyl cellulose, hereinafter abbreviated as PVDF and CMC, respectively) on the electrochemical performance of the Ti3C2Tx MXene@S composite and discovered that the electrode using the CMC binder exhibits better lithium-ion storage performance than that using the PVDF binder, which is attributed to the lower charge transfer resistance, higher ion diffusivity, and enhanced adhesion force.

A customized control and readout device for vector magnetometers based on nitrogen-vacancy centers.

A customized control and readout device, which is developed to perform real-time measurement for vector magnetometers based on nitrogen-vacancy centers, is presented in this paper. A dual-channel analog-to-digital-converter chip, which has a 25 MSa/s sampling rate and a 16 bits amplitude resolution, is integrated for analog signal acquisition. The data processing and the system control are realized using a Xilinx Kirtex-7 field-programmable-gate-array chip. Eight independent lock-in modules, a four-channel proportional-integral-derivative controller, a reference generator, and a vector field reconstruction module are integrated with the Kirtex-7 device in order to perform the real-time vector magnetic field measurement. The device has a bright future to be applied in practical applications.

The TH 22-mediated IL-22 deficiency associated with premature ovarian insufficiency.

RESEARCH QUESTION: Is deficiency of IL-22 associated with premature ovarian insufficiency (POI)? DESIGN: Levels of IL-22 and IL-22BP, IL-22-producing T cells, and IL22RA1/IL10R2 expression were measured and compared among 29 patients with POI, 42 with precursor stage of POI (pre-POI) and 46 control women. Correlation of serum IL-22 and IL-22+ CD4+ T subsets with ovarian reserve markers were further analyzed. RESULTS: IL-22 levels in serum significantly differed among control women and patients with pre-POI and POI, with the lowest concentrations in POI group (p = .019). Significant reduction of peripheral CD4+ IL-22+ T cells was observed in patients with POI (p = .010), which mainly contributed by decrease of CD4+ IL-22+ IL-17- TH 22 cells (p = .012) but not TH 17 cells (p = .125). Levels of serum IL-22 and IL-22-producing CD4+ T subsets were significantly correlated with ovarian reserve markers, including AMH, bilateral AFC, follicle-stimulating hormone (FSH), and E2 (p < .05). The specific receptor IL22RA1 expression was marginally reduced in granulosa cells from patients with pre-POI (p = .051). No difference of IL-22BP was observed either in serum (p = .216) or follicular fluid (p = .856) among groups. CONCLUSIONS: Our study first demonstrated the significant association between TH 22-mediated IL-22 deficiency and ovarian insufficiency, which provide new insights into the autoimmune disturbance and opens new avenues for exogenous IL-22 administration as potential intervention of POI.

Air-stabilized pore structure engineering of antimony-based anode by electrospinning for potassium ion batteries.

Due to the large ionic radius and associated slow reaction kinetics of potassium ions, it is a major challenge to find suitable anode materials for potassium-ion batteries. Herein, we design porous antimony-based nanofibres via a simple, low-cost and large scalable method to promote the electrochemical performance of potassium-ion batteries. Unlike those traditionally treated in inert atmospheres, using the different decomposition processes of polyacrylonitrile and polyvinylpyrrolidone in air, we obtain antimony trioxide embedded in porous carbon nanofibres (Sb2O3@PCN). The porous structure can promote the permeation of electrolyte into electrode materials and increase the active sites of the redox reaction. The porous carbonaceous fibre skeleton structure establishes a fast ion transport channel and enhances the kinetic performance. In a concentrated 5 M potassium bis(fluorosulfonyl)-imide/dimethyl carbonate electrolyte, Sb2O3@PCN exhibits a stable discharge specific capacity of 437.3 mAh g-1 at a current density of 100 mA g-1 after 50 cycles, which is much higher than that treated in a N2 atmosphere (247.5 mAh g-1). This method provides a new approach for the preparation of efficient potassium-ion battery electrode materials.

An artificial bone filling material of poly l-lactic acid/collagen/nano-hydroxyapatite microspheres: Preparation and collagen regulation on the property.

Artificial bone materials are in great need due to a lot of bone injuries. Herein, collagen/nano-hydroxyapatite (Col/nHA, C-H) composite nanospheres were obtained by in-situ mineralization, and poly L-lactic acid/collagen/nano-hydroxyapatite (PLLA/Col/nHA, P-C-H) was further prepared by high-speed shear emulsification method. The interfacial properties and structure between PLLA and nHA are regulated by the adhesive property of Col. The morphology, structure and properties of P-C-H microsphere were characterized in detail by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Brunauer-Emmett-Teller (BET) and simulated degradation of PBS in vitro. The results show that C-H is uniformly distributed in P-C-H microspheres, and a mesoporous material with a "pomegranate" structure and a particle size of 5-30 µm is self-assembled based on C-H multiple composite microspheres. It is beneficial to the sustained-release degradation of P-C-H and the retention/release of Ca2+. The 60-day PBS degradation shows that PLLA delays the degradation of nHA, making the degradation rate of P-C-H basically consist with the human bone healing cycle. The co-culture of P-C-H with MC3T3-E1 cells shows that P-C-H has high biocompatibility and no cytotoxicity. The cell viability is higher than 100 % in 72 h, indicating P-C-H has a proliferation effect on cell growth. Alkaline phosphatase and quantitative real-time PCR test show a positive promotion of P-C-H in cell proliferation and differentiation. The multi-layered P-C-H microspheres have an application potential in bone tissue engineering.

Fitness training of athletes in freestyle skiing / Treinamento de aptidão física de atletas em esqui de estilo livre / Entrenamiento de aptitud física de atletas en esquí de estilo libre

ABSTRACT Introduction: Physical training is essential to physical fitness in freestyle skiers. The domain of stability in the technical movements is a determinant of the competition, always constantly improving. Objective: Develop a physical training program adapted to freestyle skiing. Methods: Twelve freestyle skiers were selected as volunteers for the experiment. This paper compares athletes' physical qualities and individual abilities before and after physical training. Through recent research, the athletes' physical condition was comprehensively evaluated to test the effectiveness of their physical training. results: Freestyle skiers showed good anaerobic fitness. A relationship was found between the maximum number of thrusts, the degree of spin in the air, the maximum power duration, and the power decay rate (P<0.05). In the body balance test, the lower limbs showed deficiencies in anteroposterior mobility, while bipodal balance showed no significantly statistical differences (P>0.05). Conclusion: This paper systematically studies body composition, the center of gravity strength, anaerobic capacity, and balance in freestyle skiers. The results provide a good assessment of the effect of fitness training on freestyle ski athletes. These results have particular guiding significance for formulating and implementing training programs focused on the sport. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: O treinamento físico é parte essencial da aptidão física em esquiadores de estilo livre. O domínio da estabilidade nos movimentos técnicos é determinante sobre as competições, estando sempre em constante aprimoramento. Objetivo: Elaborar um programa de treinamento físico adaptado ao esporte do esqui de estilo livre. Métodos: Selecionou-se 12 esquiadores de estilo livre como voluntários ao experimento. Este artigo compara as qualidades físicas e habilidades individuais dos atletas antes e depois do treinamento físico. Através de pesquisas recentes, avaliou-se de forma abrangente a condição física dos atletas para testar a eficácia de seu treinamento físico. Resultados: Os esquiadores de estilo livre apresentaram uma boa praticabilidade anaeróbica. Foi encontrada uma relação particular entre o número máximo de propulsões e o grau de giro no ar, a duração máxima da potência e a taxa de decaimento da potência (P<0,05). No teste de equilíbrio corporal, os membros inferiores apresentaram deficiências de mobilidade anteroposterior, enquanto o equilíbrio bipodal não apresentou diferenças significativamente estatísticas (P>0,05). Conclusão: Este artigo fornece um estudo sistemático da composição corporal, força do centro gravitacional, capacidade anaeróbica e equilíbrio em esquiadores de estilo livre. Os resultados proporcionam uma boa avaliação do efeito de treinamento de aptidão física nos atletas de esqui de estilo livre. Estes resultados têm um significado orientador particular para a formulação e implementação de programas de treinamento focados na modalidade. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: El entrenamiento físico es una parte esencial de la aptitud física en los esquiadores de estilo libre. El dominio de la estabilidad en los movimientos técnicos es determinante sobre las competiciones, estando siempre en constante mejora. Objetivo: Desarrollar un programa de entrenamiento físico adaptado al deporte del esquí de estilo libre. Métodos: Se seleccionaron doce esquiadores de estilo libre como voluntarios para el experimento. Este artículo compara las cualidades físicas y las capacidades individuales de los atletas antes y después del entrenamiento físico. Mediante una investigación reciente, se evaluó exhaustivamente la condición física de los atletas para comprobar la eficacia de su entrenamiento físico. Resultados: Los esquiadores de estilo libre mostraron una buena aptitud anaeróbica. Se encontró una relación particular entre el número máximo de empujes y el grado de giro en el aire, la duración de la potencia máxima y la tasa de disminución de la potencia (P<0,05). En la prueba de equilibrio corporal, los miembros inferiores mostraron deficiencias en la movilidad anteroposterior, mientras que el equilibrio bipodal no mostró diferencias estadísticas significativas (P>0,05). Conclusión: Este artículo proporciona un estudio sistemático de la composición corporal, la fuerza gravitatoria central, la capacidad anaeróbica y el equilibrio en esquiadores de estilo libre. Los resultados proporcionan una buena evaluación del efecto del entrenamiento físico en los atletas de esquí de estilo libre. Estos resultados tienen una especial importancia orientativa para la formulación y aplicación de programas de entrenamiento centrados en este deporte. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Clinical application of artificial neural network (ANN) modeling to predict BRCA1/2 germline deleterious variants in Chinese bilateral primary breast cancer patients.

BACKGROUND: Bilateral breast cancer (BBC), as well as ovarian cancer, are significantly associated with germline deleterious variants in BRCA1/2, while BRCA1/2 germline deleterious variants carriers can exquisitely benefit from poly (ADP-ribose) polymerase (PARP) inhibitors. However, formal genetic testing could not be carried out for all patients due to extensive use of healthcare resources, which in turn results in high medical costs. To date, existing BRCA1/2 deleterious variants prediction models have been developed in women of European or other descent who are quite genetically different from Asian population. Therefore, there is an urgent clinical need for tools to predict the frequency of BRCA1/2 deleterious variants in Asian BBC patients balancing the increased demand for and cost of cancer genetics services. METHODS: The entire coding region of BRCA1/2 was screened for the presence of germline deleterious variants by the next generation sequencing in 123 Chinese BBC patients. Chi-square test, univariate and multivariate logistic regression were used to assess the relationship between BRCA1/2 germline deleterious variants and clinicopathological characteristics. The R software was utilized to develop artificial neural network (ANN) and nomogram modeling for BRCA1/2 germline deleterious variants prediction. RESULTS: Among 123 BBC patients, we identified a total of 20 deleterious variants in BRCA1 (8; 6.5%) and BRCA2 (12; 9.8%). c.5485del in BRCA1 is novel frameshift deleterious variant. Deleterious variants carriers were younger at first diagnosis (P = 0.0003), with longer interval between two tumors (P = 0.015), at least one medullary carcinoma (P = 0.001), and more likely to be hormone receptor negative (P = 0.006) and HER2 negative (P = 0.001). Area under the receiver operating characteristic curve was 0.903 in ANN and 0.828 in nomogram modeling individually (P = 0.02). CONCLUSION: This study shows the spectrum of the BRCA1/2 germline deleterious variants in Chinese BBC patients and indicates that the ANN can accurately predict BRCA deleterious variants than conventional statistical linear approach, which confirms the BRCA1/2 deleterious variants carriers at the lowest costs without adding any additional examinations.