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Adult hematopoietic stem and progenitor cells (HSPCs) reside in the bone marrow (BM) ensuring homeostasis of blood production and immune response throughout life. Sex differences in immunocompetence and mortality are well-documented in humans. However, whether HSPCs behave dimorphically between sexes during aging remains unknown. Here, we show that a significant expansion of BM-derived HSPCs occurs in the middle age of female but in the old age of male mice. We then show that a decline of HSPCs in male mice, as indicated by the expression levels of select hematopoietic genes, occurs much earlier in the aging process than that in female mice. Sex-mismatched heterochronic BM transplantations indicate that the middle-aged female BM microenvironment plays a pivotal role in sustaining hematopoietic gene expression during aging. Furthermore, a higher concentration of the pituitary sex hormone follicle-stimulating hormone (FSH) in the serum and a concomitant higher expression of its receptor on HSPCs in the middle-aged and old female mice than age-matched male mice, suggests that FSH may contribute to the sexual dimorphism in aging hematopoiesis. Our study reveals that HSPCs in the BM niches are possibly regulated in a sex-specific manner and influenced differently by sex hormones during aging hematopoiesis.

A linear programming model that selects the optimal cropping plan and feeds allocation for diets to minimize the whole dairy farm feed costs was developed. The model was virtually applied on 29 high-yielding Holstein-Friesian herds, confined, total mixed ration dairy farms. The average herd size was 313.2 ± 144.1 lactating cows and the average land size was 152.2 ± 92.5 ha. Farm characteristics such as herd structure, nutritional grouping strategies, feed consumption, cropping plan, intrinsic farm limitations (e.g., silage and hay storage availability, water for irrigation, manure storage) and on farm produced forage costs of production were collected from each farm for the year 2017. Actual feeding strategies, land availability, herd structure, crop production costs and yields, and milk and feed market prices for the year 2017 were used as model inputs. Through optimization, the feeding system was kept equal to the actual farm practice. The linear program formulated diets for each animal group to respect actual herd dry matter intake and fulfill actual consumption of crude protein, rumen-degradable and rumen-undegradable fractions of crude protein, net energy for lactation, neutral detergent fiber, acid detergent fiber, forage neutral detergent fiber, and nonfiber carbohydrate. Production levels and herd composition were considered to remain constant as the nutritional requirement would remain unchanged. The objective function was set to minimize the whole-farm feed costs including cash crop sales as income, and crop production costs and purchased feed costs as expenses. Optimization improved income over feed costs by reducing herd feed costs by 7.8 ± 6.4%, from baseline to optimized scenario, the improved was explained by lower feed costs per kilogram of milk produced due to a higher feed self-sufficiency and higher income from cash crop. In particular, the model suggested to maximize, starting from baseline to optimized scenario, the net energy for lactation (+8.5 ± 6.3%) and crude protein (+3.6 ± 3.1%) produced on farm, whereas total feed cost (€/100 kg of milk) was greater in the baseline (20.4 ± 2.3) than the optimized scenario (19.0 ± 1.9), resulting in a 6.7% feed cost reduction with a range between 0.49% and 21.6%. This meant €109 ± 96.9 greater net return per cow per year. The implementation of the proposed linear programming model for the optimal allocation of the nutritional resources and crops in a dairy herd has the potential to reduce feed cost of diets and improve the farm feed self-sufficiency.

Mesenchymal stem cell extracellular vesicles attenuate pulmonary hypertension, but their ability to reverse established disease in larger animal models and the duration and mechanism(s) of their effect are unknown. We sought to determine the efficacy and mechanism of mesenchymal stem cells’ extracellular vesicles in attenuating pulmonary hypertension in rats with Sugen/hypoxia-induced pulmonary hypertension. Male rats were treated with mesenchymal stem cell extracellular vesicles or an equal volume of saline vehicle by tail vein injection before or after subcutaneous injection of Sugen 5416 and exposure to 3 weeks of hypoxia. Pulmonary hypertension was assessed by right ventricular systolic pressure, right ventricular weight to left ventricle + septum weight, and muscularization of peripheral pulmonary vessels. Immunohistochemistry was used to measure macrophage activation state and recruitment to lung. Mesenchymal stem cell extracellular vesicles injected before or after induction of pulmonary hypertension normalized right ventricular pressure and reduced right ventricular hypertrophy and muscularization of peripheral pulmonary vessels. The effect was consistent over a range of doses and dosing intervals and was associated with lower numbers of lung macrophages, a higher ratio of alternatively to classically activated macrophages (M2/M1 = 2.00 ± 0.14 vs. 1.09 ± 0.11; P

A challenge for data sharing in systems neuroscience is the multitude of different data formats used. Neurodata Without Borders: Neurophysiology 2.0 (NWB:N) has emerged as a standardized data format for the storage of cellular-level data together with meta-data, stimulus information, and behavior. A key next step to facilitate NWB:N adoption is to provide easy to use processing pipelines to import/export data from/to NWB:N. Here, we present a NWB-formatted dataset of 1863 single neurons recorded from the medial temporal lobes of 59 human subjects undergoing intracranial monitoring while they performed a recognition memory task. We provide code to analyze and export/import stimuli, behavior, and electrophysiological recordings to/from NWB in both MATLAB and Python. The data files are NWB:N compliant, which affords interoperability between programming languages and operating systems. This combined data and code release is a case study for how to utilize NWB:N for human single-neuron recordings and enables easy re-use of this hard-to-obtain data for both teaching and research on the mechanisms of human memory., Measurement(s)medial temporal lobe • memory • amygdala • hippocampusTechnology Type(s)single-unit recordingFactor Type(s)confidence • remembered/forgotten • old/new • visual category • stimulus onset (visual)Sample Characteristic - OrganismHomo sapiens Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.11835801

The loss of skeletal muscle mass and function is a serious consequence of chronic diseases and aging. BST204 is a purified ginseng (the root of Panax ginseng) extract that has been processed using ginsenoside-[Formula: see text]-glucosidase and acid hydrolysis to enrich ginsenosides Rg3 and Rh2 from the crude ginseng. BST204 has a broad range of health benefits, but its effects and mechanism on muscle atrophy are currently unknown. In this study, we have examined the effects and underlying mechanisms of BST204 on myotube formation and myotube atrophy induced by tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]). BST204 promotes myogenic differentiation and multinucleated myotube formation through Akt activation. BST204 prevents myotube atrophy induced by TNF-[Formula: see text] through the activation of Akt/mTOR signaling and down-regulation of muscle-specific ubiquitin ligases, MuRF1, and Atrogin-1. Furthermore, BST204 treatment in atrophic myotubes suppresses mitochondrial reactive oxygen species (ROS) production and regulates mitochondrial transcription factors such as NRF1 and Tfam, through enhancing the activity and expression of peroxisome proliferator-activated receptor-[Formula: see text] coactivator1[Formula: see text] (PGC1[Formula: see text]). Collectively, our findings indicate that BST204 improves myotube formation and PGC1[Formula: see text]-mediated mitochondrial function, suggesting that BST204 is a potential therapeutic or neutraceutical remedy to intervene muscle weakness and atrophy.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is mediated by the entry receptor angiotensin-converting enzyme 2 (ACE2). Although attachment factors and coreceptors facilitating entry are extensively studied, cellular entry factors inhibiting viral entry are largely unknown. Using a surfaceome CRISPR activation screen, we identified human LRRC15 as an inhibitory attachment factor for SARS-CoV-2 entry. LRRC15 directly binds to the receptor-binding domain (RBD) of spike protein with a moderate affinity and inhibits spike-mediated entry. Analysis of human lung single-cell RNA sequencing dataset reveals that expression of LRRC15 is primarily detected in fibroblasts and particularly enriched in pathological fibroblasts in COVID-19 patients. ACE2 and LRRC15 are not coexpressed in the same cell types in the lung. Strikingly, expression of LRRC15 in ACE2-negative cells blocks spike-mediated viral entry in ACE2+ cell in trans, suggesting a protective role of LRRC15 in a physiological context. Therefore, LRRC15 represents an inhibitory attachment factor for SARS-CoV-2 that regulates viral entry in trans.

With the aim of improving the aerodynamic performance of axial turbomachinery, a new type of blade is designed using the equal–variable circulation method. Taking an axial flow fan as the research object, this article describes the development of a new type of turbomachinery by changing the design method and producing a blade with forward sweep. The aerodynamic performance of the fan is simulated and compared with the experimental data. The numerical results show that the equal circulation design method improves the aerodynamic performance of the blade roots, while the variable circulation design method enhances the aerodynamic performance of the blade tips. By adopting the equal–variable circulation design method, the total pressure of the experimental fan is increased by about 4%, while the efficiency remains unchanged. Forward-swept blades with an equal–variable circulation design also improve performance over the conventional blades by changing the center-of-gravity stacking line. At low flow rates, the efficiency of the experimental fan can be increased by 7.5%, and the working range of the flow is expanded. Under high flow rates, the restriction of the blade tip on the airflow is decreased and the fluidity is slightly reduced.

OBJECTIVE: To explore the role of miR-671-5p in regulating the migration and invasion of osteosarcoma and the underlying mechanisms. METHODS: The differentially expressed microRNAs (miRNAs) in osteosarcoma were screened in the NCBI online database, and the target proteins of these miRNAs were predicted and their functions were analyzed. Osteosarcoma cells were transfected with a plasmid overexpressing miR-671-5p, and the transfection efficiency was assessed using quantitative real-time PCR (qRT-PCR). The changes in the migration and invasion of the transfected cells were examined with Transwell assay, and the expressions of proteins related with epithelial-mesenchymal transition (EMT) were detected using Western blotting. Dual-luciferase reporter assay was performed to determine whether the 3'UTR of SMAD3 contained a targeted binding site of miR-671-5p. RESULTS: MiR-671-5p was significantly down-regulated in both osteosarcoma tissues and osteosarcoma cells (P < 0.05). The osteosarcoma cells overexpressing miR-671-5p showed significantly reduced migration and invasion abilities (P < 0.05) with obviously lowered expressions of EMT-related proteins (P < 0.05). SMAD3 was highly expressed in osteosarcoma cells (P < 0.05), and dual-luciferase reporter assay confirmed the presence of a targeted binding site between miR-671-5p and the 3'UTR of SMAD3 (P < 0.05). In osteosarcoma cells transfected with a SMAD3-overexpressing plasmid (P < 0.05), the high expression of SMAD3 significantly inhibited by miR-671-5p overexpression (P < 0.05). Transwell assay demonstrated that SMAD3 overexpression significantly promoted the migration and invasion of osteosarcoma cells (P < 0.05), and while miR-671-5p overexpression obviously reversed this effect (P < 0.05). CONCLUSION: MiR-671-5p can inhibit the invasion and migration of osteosarcoma cells by negatively regulating SMAD3.

SARS-CoV-2 infection is mediated by the entry receptor ACE2. Although attachment factors and co-receptors facilitating entry are extensively studied, cellular entry factors inhibiting viral entry are largely unknown. Using a surfaceome CRISPR activation screen, we identified human LRRC15 as an inhibitory receptor for SARS-CoV-2 entry. LRRC15 directly binds to the receptor-binding domain (RBD) of spike protein with a moderate affinity and inhibits spike-mediated entry. Analysis of human lung single cell RNA sequencing dataset reveals that expression of LRRC15 is primarily detected in fibroblasts and particularly enriched in pathological fibroblasts in COVID-19 patients. ACE2 and LRRC15 are not co-expressed in the same cell types in the lung. Strikingly, expression of LRRC15 in ACE2-negative cells blocks spike-mediated viral entry in ACE2+ cell in trans, suggesting a protective role of LRRC15 in a physiological context. Therefore, LRRC15 represents an inhibitory receptor for SARS-CoV-2 regulating viral entry in trans.

OBJECTIVE: To design novel antimicrobial peptides with high activity and low toxicity and evaluate their effect against Streptococcus mutans and other oral bacteria for prevention and treatment of dental caries. METHODS: We synthesized two antimicrobial peptides (KR-1 and KR-2) using Dhvar4 (a histatins5 mimic) as the template. The antimicrobial peptides with high activity and low toxicity were screened using minimal inhibitory concentration (MIC) test, hemolysis test, and CCK-8 assay. Streptococcus mutans biofilms cultured in 96-well plates were divided into experimental group (KR-1) and positive control group (CHX) and treated with concentration gradients (0.6×, 0.8×, 1× and 2× MICs) of KR-1 and CHX, respectively. Crystal violet staining was used for quantitative analysis of the changes of the biofilms after the treatments. The structural changes of the biofilms were observed with laser confocal microscopy after KR-1 treatment at 10 × MIC. The antimicrobial activity of KR-1 against oral Streptococcus was analyzed based on the time required for sterilization after KR-1 treatment. RESULTS: The MIC of KR-1 and KR-2 for S. mutans was 3.2 μmol/L and 12.8 μmol/L, respectively. Under the effective concentration, KR-1 and KR-2 resulted in hemolysis rates of 0.35% and 48.8% in rabbit red blood cells and lowered the survival rates of gingival fibroblasts to 88.7% and 21.94%, respectively. KR-1 treatment significantly reduced biofilm formation with a minimum biofilm inhibition concentration (MBIC(50)) lower than 1.92 μmol/L, and showed an even stronger antimicrobial than CHX at the concentration of 2.56 μmol/L (P=0.001). Confocal laser scanning microscopy revealed that the biofilm structure became loosened after KR-1 treatment, which was capable of killing about 90% of the bacteria within 5 min. CONCLUSION: The antimicrobial peptide KR-1 has a stronger antibacterial activity and a low toxicity with a good inhibitory effect against S. mutans biofilm.

Background Myelofibrosis (MF), a rare disorder characterized by bone marrow fibrosis, has been implicated as a cause of pulmonary hypertension (PH). To date, studies examining this association have not looked at the impact of PH on survival in MF. We examined the relationship between MF and PH by echocardiogram (echo) using a retrospective patient database and examined the influence of PH on overall survival. Patients and Methods In this single-center retrospective chart review, we identified 65 patients with biopsy-proven primary and secondary MF, 31 of whom underwent transthoracic echo. After accounting for chronic obstructive pulmonary disease and left-sided or valvular heart dysfunction, which excluded 6 patients, we identified 14 patients (56%) who had echo evidence of group 5 PH (ie, PH due to unclear or multifactorial mechanisms), 8 with primary MF and 6 with secondary MF. MF patients with PH trended toward being predominantly female, being older, and less often having constitutional symptoms compared to the non-PH cohort. Results There was no effect of the presence of PH on overall survival in the entire MF cohort or in any subgroup analyzed, including primary MF versus secondary MF and primary MF intermediate risk patients. Conclusion Given the high prevalence of MF-associated PH, there may be a larger role for routine echo screening in MF patients. Further, the underlying association between PH and MF may signify an endothelial plasticity or increased telomerase activity as part of the pathogenesis of MF.

Hydrogen has been considered as a potential candidate for the replacement of fossil fuels in future due to its renewability, abundance, ease in production, environmental friendliness and high energ...

SH2‐containing inositol‐5′‐phosphatase‐1 (SHIP‐1) controls the phosphatidylinositol‐3′‐kinase (PI3K) initiated signaling pathway by limiting cell membrane recruitment and activation of Akt. Despite the fact that many of the growth factors important to cartilage development and functions are able to activate the PI3K signal transduction pathway, little is known about the role of PI3K signaling in chondrocyte biology and its contribution to mammalian skeletogenesis. Here, we report that the lipid phosphatase SHIP‐1 regulates chondrocyte hypertrophy and skeletal development through its expression in osteochondroprogenitor cells. Global SHIP‐1 knockout led to accelerated chondrocyte hypertrophy and premature formation of the secondary ossification center in the bones of postnatal mice. Drastically higher vascularization and greater number of c‐kit + progenitors associated with sinusoids in the bone marrow also indicated more advanced chondrocyte hypertrophic differentiation in SHIP‐1 knockout mice than in wild‐type mice. In corroboration with the in vivo phenotype, SHIP‐1 deficient PDGFRα + Sca‐1 + osteochondroprogenitor cells exhibited rapid differentiation into hypertrophic chondrocytes under chondrogenic culture conditions in vitro. Furthermore, SHIP‐1 deficiency inhibited hypoxia‐induced cellular activation of Akt and extracellular‐signal‐regulated kinase (Erk) and suppressed hypoxia‐induced cell proliferation. These results suggest that SHIP‐1 is required for hypoxia‐induced growth signaling under physiological hypoxia in the bone marrow. In conclusion, the lipid phosphatase SHIP‐1 regulates skeletal development by modulating chondrogenesis and the hypoxia response of the osteochondroprogenitors during endochondral bone formation., In this study, we found that lipid phosphatase SH2‐containing inositol‐5′‐phosphatase‐1 (SHIP‐1) negatively regulates the hypertrophic process of growth plate chondrocytes. SHIP‐1 deficiency accelerates the formation of the secondary ossification center, and SHIP‐1 KO mice have elevated vascularization and more c‐kit + progenitor cells in the bone marrow compartment. SHIP‐1 is also required for hypoxia‐induced Akt/Erk activation and cell proliferation.

Novel tough bio-based polyesters poly(ethylene 2,5-thiophenedicarboxylate-co-1,4-cyclohexanedimethylene 2,5-thiophenedicarboxylate)s (PECTFs) were synthesized from 2,5-thiophenedicarboxylic acid (TDCA), 1,4-cyclohexanedimethanol (CHDM) and ethylene glycol (EG). The microstructure, thermal and mechanical properties were investigated. Poly(ethylene 2,5-thiophenedicarboxylate) (PETF) displayed the glass transition temperature (~64 °C) and tensile strength (~72 MPa) similar to poly(ethylene terephthalate) (PET). However, the nonlinear structure of TDCA resulted in an angle of 148° between carboxylic acid carbons and the S atom resulted in a permanent dipole, so the thiophene ring-flipping was hindered and the low elongation at break (~24%) was observed for PETF. The peak corresponding to the secondary relaxation shifted to lower temperature due to the incorporation of CHDM, which yielded ductile copolyesters with high elongation at break. When the CHDM content was equal to or higher than 29%, a high elongation at break (>160%) was observed.

During a nuclear emergency, an internal exposure detection device with on-site and rapid measurements should be developed to assess the level of internal exposure of people in radioactively contaminated areas. Based on MCNP simulations, this work designed a shielding structure of a NaI(Tl) type vehicle-mounted whole-body counter (VM-WBC) and it has good shielding performance against the background radiation. The mass of the shielding structure was less than 800 kg, and the minimum detectable activity (MDA) of 60Co and 137Cs obtained by simulation for a 10 min measurement was less than 50 Bq. And we also study its counting efficiency calibration by simulating radiation computing phantoms with Chinese and American reference physiological characteristics. Equations that fit counting efficiency, body build index, and photon energy were also developed. The relative efficiency deviation between the equation and the MCNP simulation was less than 5%.

Flow separation commonly affects the stability of turbomachines, especially under low-flowrate conditions. Compared with conventional blades, a forward-swept blade is more efficient at high flowrates. However, experiments and numerical simulations show that a forward-swept blade produces an unstable region under low flowrate. In this paper, the topological analysis is used to analyze the structure and size of flow separation in forward swept blades. Three-dimensional structure and formation mechanism of vortices in forward-swept blades are analyzed using the cross-section flow pattern method. For forward-swept blades, flow separation mainly occurs at the blade tip and corner, accompanied by clear velocity fluctuations, the break-up of shed vortices, and diffusion. With decreasing flowrate, the shedding vortices move forward and the speed of vortex annihilation gradually decreases. In addition, the number of singularities in the rotor passage increases with the decrease of flow rate, and the region affected by shedding vortex increases. The rotating direction of internal vortex in turbomachinery is fixed. The pressure surface, passage vortex, and concentrated shedding vortex were found to rotate clockwise, whereas the suction surface, corner vortex, and shedding vortex rotate in a counterclockwise direction.

Increased use and improved methodology of carbonate clumped isotope thermometry has greatly enhanced our ability to interrogate a suite of Earth‐system processes. However, interlaboratory discrepancies in quantifying carbonate clumped isotope (Δ47) measurements persist, and their specific sources remain unclear. To address interlaboratory differences, we first provide consensus values from the clumped isotope community for four carbonate standards relative to heated and equilibrated gases with 1,819 individual analyses from 10 laboratories. Then we analyzed the four carbonate standards along with three additional standards, spanning a broad range of δ47 and Δ47 values, for a total of 5,329 analyses on 25 individual mass spectrometers from 22 different laboratories. Treating three of the materials as known standards and the other four as unknowns, we find that the use of carbonate reference materials is a robust method for standardization that yields interlaboratory discrepancies entirely consistent with intralaboratory analytical uncertainties. Carbonate reference materials, along with measurement and data processing practices described herein, provide the carbonate clumped isotope community with a robust approach to achieve interlaboratory agreement as we continue to use and improve this powerful geochemical tool. We propose that carbonate clumped isotope data normalized to the carbonate reference materials described in this publication should be reported as Δ47 (I‐CDES) values for Intercarb‐Carbon Dioxide Equilibrium Scale., Key Points The exclusive use of carbonate reference materials is a robust method for the standardization of clumped isotope measurementsMeasurements using different acid temperatures, designs of preparation lines, and mass spectrometers are statistically indistinguishableWe propose new consensus values for a set of seven carbonate reference materials and updated guidelines to report clumped isotope measurements

International audience; Irradiation Assisted Stress Corrosion Cracking (IASCC) is a material degradation phenomenon affecting austenitic stainless steels used in nuclear Pressurized Water Reactors (PWR), leading to the initiation and propagation of intergranular cracks. Such phenomenon belongs to the broader class of InterGranular Stress Corrosion Cracking (IGSCC). A micromechanical analysis of IGSCC of an irradiated austenitic stainless steel is performed in this study to assess local cracking conditions. A 304L proton irradiated sample tested in PWR environment and showing intergranular cracking is investigated. Serial sectioning, Electron BackScatter Diffraction (EBSD) and a two-step misalignment procedure are performed to reconstruct the 3D microstructure over an extended volume, to assess statistically cracking criteria. A methodology is alsodeveloped to compute Grain Boundary (GB) normal orientations based on the EBSD measurements. The statistical analysis shows that cracking occurs preferentially for GB normals aligned with the mechanical loading axis, but also for low values of the Luster-Morris slip transmission parameter. Micromechanical simulations based on the reconstructed 3D microstructure, FFT-based solver and crystal plasticity constitutive equations modified to account for slip transmission at grain boundaries are finally performed. These simulations rationalize the correlation obtained experimentally into a single stress-based criterion. The actual strengths and weaknesses of such micromechanical approach are discussed.

Introduction: Pulmonary hypertension (PH) is a currently incurable disease with high morbidity and mortality. Treatment with extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) appeared to be effective and promising. Objective: We aimed at evaluating whether MSC-EVs could improve right ventricle (RV) and pulmonary artery (PA) functions in mice with PAH induced by monocrotaline (MCT). Methods: FVB mice (M/F – 6 weeks) received MCT injections 1x/week for 4 weeks (60mg/kg sc.) and were treated with MSCs-EVs 24 hours after each MCT injection (3x10 6 cells in 100μL PBS 1x, iv.). The experimental groups were: Control (vehicle-vehicle; n=9); MCT (MCT-vehicle; n=10); Control EVs (vehicle-EVs; n=8); MCT EVs (MCT-EVs; n=10); PA acceleration time (PAT), PA ejection time (PET) and tricuspid annular plane systolic excursion (TAPSE) were assessed by echocardiography 28 days after first MCT injection; Fulton index was used to calculate RV hypertrophy, and pulmonary vascular remodeling (WT/D) was assessed by histology. Results: PAT and PAT/PET were decreased by 22.6±5.7% and 15.6±4.9%, respectively, in MCT group compared to Control (p Conclusion: Treatment with MSC-EVs protects against the development of PH and improves PA and the RV function in MCT-treated mice.

Tricritical phenomenon appearing in multiple phases is a fundamental and attractive issue in condensed-matter physics. Monopnictide DySb, a candidate for potential magnetic topological semimetal with an antiferromagnetic ground state, has been found to possess complex and intriguing field-induced magnetic phase transitions. In this work, critical behaviors of single-crystal DySb are investigated systematically, which generate a series of critical exponents including $\ensuremath{\beta}=0.244(2)$, $\ensuremath{\gamma}=0.827(2)$, and $\ensuremath{\delta}=4.425(1)$ for $H\ensuremath{\parallel}[001]$. The deduced critical exponents verified by Widom law and scaling equations are close to a tricritical mean-field model, suggesting a field-induced tricritical phenomenon in DySb. Based on the universality principle, a detailed $H\text{\ensuremath{-}}T$ phase diagram around the phase transition is constructed for $H\ensuremath{\parallel}[001]$, in which a tricritical point is revealed at temperature and field of (7.5 K, 51.4 kOe) on intersected boundaries of antiferromagnetic, forced ferromagnetic, and paramagnetic phases. Moreover, a triple point is found at the intersection (9.2 K, 19.7 kOe) of paramagnetic and two kinds of antiferromagnetic states. Such a fascinating phase diagram is indicative of delicate competition and balance between multiple magnetic interactions in this system, and lays a solid foundation for future research in topological transition and criticality.

The micro-elimination strategy is an effective approach to rapidly reduce the incidence and mortality of specific populations infected with hepatitis C virus (HCV). This article combines the current status of hepatitis C prevention and treatment in Guizhou Province, and introduces the current domestic and foreign hepatitis C micro-elimination models. It is worth mentioning that the Guizhou Provincial Medical Quality Control Center for Infectious Diseases jointly formulated the "Guizhou Province Chronic Hepatitis C Health Education Standards" to improve the awareness of health care workers and patients about the disease, increase the screening rate, and increase the patients willingness to receive treatment and accomplish the World Health Organization's goal of eliminating hepatitis C threat by 2030.丙型肝炎微消除策略是为特定的丙型肝炎患者提供针对性服务，更迅速有效地降低丙型肝炎的发病率和病死率。现借鉴目前国内外丙型肝炎微消除模式，结合贵州省丙型肝炎防治的现状，联合当地感染性疾病医疗质量控制中心共同制定了该省慢性丙型肝炎健康教育规范，旨在提高医护人员、患者对疾病的认识，进一步提高丙型肝炎筛查率，增强患者治疗意愿，早日实现世界卫生组织2030年消除丙型肝炎公共卫生威胁的目标。.

Biophysically based computational models of nerve fibers are important tools for designing electrical stimulation therapies, investigating drugs that affect ion channels, and studying diseases that affect neurons. Although peripheral nerves are primarily composed of unmyelinated axons (i.e., C-fibers), most modeling efforts focused on myelinated axons. We implemented the single-compartment model of vagal afferents from Schild et al. (1994) (Schild JH, Clark JW, Hay M, Mendelowitz D, Andresen MC, Kunze DL. J Neurophysiol 71: 2338–2358, 1994) and extended the model into a multicompartment axon, presenting the first cable model of a C-fiber vagal afferent. We also implemented the updated parameters from the Schild and Kunze (1997) model (Schild JH, Kunze DL. J Neurophysiol 78: 3198–3209, 1997). We compared the responses of these novel models with those of three published models of unmyelinated axons (Rattay F, Aberham M. IEEE Trans Biomed Eng 40: 1201–1209, 1993; Sundt D, Gamper N, Jaffe DB. J Neurophysiol 114: 3140–3153, 2015; Tigerholm J, Petersson ME, Obreja O, Lampert A, Carr R, Schmelz M, Fransén E. J Neurophysiol 111: 1721–1735, 2014) and with experimental data from single-fiber recordings. Comparing the two models by Schild et al. (1994, 1997) revealed that differences in rest potential and action potential shape were driven by changes in maximum conductances rather than changes in sodium channel dynamics. Comparing the five model axons, the conduction speeds and strength-duration responses were largely within expected ranges, but none of the models captured the experimental threshold recovery cycle—including a complete absence of late subnormality in the models—and their action potential shapes varied dramatically. The Tigerholm et al. (2014) model best reproduced the experimental data, but these modeling efforts make clear that additional data are needed to parameterize and validate future models of autonomic C-fibers. NEW & NOTEWORTHY Peripheral nerves are primarily composed of unmyelinated axons, and there is growing interest in electrical stimulation of the autonomic nervous system to treat various diseases. We present the first cable model of an unmyelinated vagal nerve fiber and compare its ion channel isoforms and conduction responses with other published models of unmyelinated axons, establishing important tools for advancing modeling of autonomic nerves.

This study is aimed at analysing the endogenous metabolites profiling of patients with diabetic osteoporosis, so as to provide the reference for pathogenesis research of diabetic osteoporosis.The 1H-NMR metabolomics technology, combined with pattern recognition analysis and SIMCA-P 12.0 statistical analysis, were employed to identify the metabolites differences between diabetic patients with disordered bone metabolism (research group) and healthy volunteers (normal group) in this study.Compared with normal group, the results show that in research group, the levels of O-acetyl glycoprotein, proline, 1-methyl histidine, tricarboxylic acid cycle (TCA cycle) product (citric acid and α-ketoglutaric acid) decline, while the levels of branched chain amino acids (leucine, isoleucine, valine), glucose, choline, creatine, inositol, glutamine, aspartic acid, alanine, glycine, and citrulline increase.There are disordered metabolic pathways and imbalanced bone synthetic materials and regulatory substances in diabetic patients with bone metabolic abnormality. These metabolic abnormalities could be the specific indicators in early diagnosis of diabetic osteoporosis.

The dewetting dynamics of a supported bilayer polymer thin film on a solid substrate is investigated using grazing incidence x-ray photon correlation spectroscopy. We find that the top layer dewets via the spinodal mechanism. The kinetics of the dewetting is studied by monitoring the time evolution of the surface diffuse x-ray scattering intensity. We study the time evolution of fluctuations about the average surface structure by measuring the two-time x-ray intensity fluctuation correlation functions. Using these two-time correlation functions we quantify the crossover from early-time diffusive dynamics to hydrodynamics. The early diffusive regime satisfies dynamic universality. The two-time correlation functions also quantify the onset of hydrodynamic effects. The hydrodynamic regime is observed during the spinodal dewetting process as these interactions are not screened.

Aims Pulmonary arterial hypertension (PAH) is a fatal disease without a cure. Previously, we found that transcription factor RUNX1-dependent haematopoietic transformation of endothelial progenitor cells may contribute to the pathogenesis of PAH. However, the therapeutic potential of RUNX1 inhibition to reverse established PAH remains unknown. In the current study, we aimed to determine whether RUNX1 inhibition was sufficient to reverse Sugen/hypoxia (SuHx)-induced pulmonary hypertension (PH) in rats. We also aimed to demonstrate possible mechanisms involved. Methods and results We administered a small molecule specific RUNX1 inhibitor Ro5-3335 before, during, and after the development of SuHx-PH in rats to investigate its therapeutic potential. We quantified lung macrophage recruitment and activation in vivo and in vitro in the presence or absence of the RUNX1 inhibitor. We generated conditional VE-cadherin-CreERT2; ZsGreen mice for labelling adult endothelium and lineage tracing in the SuHx-PH model. We also generated conditional Cdh5-CreERT2; Runx1(flox/flox) mice to delete Runx1 gene in adult endothelium and LysM-Cre; Runx1(flox/flox) mice to delete Runx1 gene in cells of myeloid lineage, and then subjected these mice to SuHx-PH induction. RUNX1 inhibition in vivo effectively prevented the development, blocked the progression, and reversed established SuHx-induced PH in rats. RUNX1 inhibition significantly dampened lung macrophage recruitment and activation. Furthermore, lineage tracing with the inducible VE-cadherin-CreERT2; ZsGreen mice demonstrated that a RUNX1-dependent endothelial to haematopoietic transformation occurred during the development of SuHx-PH. Finally, tissue-specific deletion of Runx1 gene either in adult endothelium or in cells of myeloid lineage prevented the mice from developing SuHx-PH, suggesting that RUNX1 is required for the development of PH. Conclusion By blocking RUNX1-dependent endothelial to haematopoietic transformation and pulmonary macrophage recruitment and activation, targeting RUNX1 may be as a novel treatment modality for pulmonary arterial hypertension.