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Gaining insight into the underlying mechanisms driving nanoindentation-induced behavior in tungsten is essential for comprehending its mechanical properties. Although the plasticity of conventional pure tungsten under nanocontact conditions is well understood, these theoretical constructs may become inadequate when applied to irradiated tungsten due to the interplay between helium bubbles and dislocations. Here, we employed an integrated approach, combining crystal defect theories, molecular dynamics simulations, and machine learning, to explore the initiation and progression of dislocations in tungsten containing helium bubbles during nanoindentation, focusing on elucidating the impact of helium bubbles. In contrast to the typical dislocation nucleation in pure tungsten, the presence of helium bubbles mitigates local shear strain, thereby hindering dislocation nucleation and propagation, leading to a reduction of indentation force. Additionally, we conducted a comparative analysis between samples with and without helium bubbles, examining factors such as atomic displacement, strain localization parameters, dislocation line length, and stress component distribution. More importantly, a significant outcome of our study is the establishment of a relationship between the consistent alteration in the shape of helium bubbles and their size during micro-scale nanoindentation, achieved through machine learning techniques. Our findings reveal that the area occupied by helium bubbles post-nanoindentation is inversely correlated with indentation depth and directly linked to helium bubble size. These discoveries represent a notable advancement in understanding the effects of irradiation to a certain degree.

The interaction between irradiation defects and dislocations could lead to macroscopic hardening and embrittlement. In this study, molecular dynamics (MD) and machine learning were conducted to study three-dimensional void- and Cu-cluster-induced kinetics models under interaction with dislocations in body-centered cubic Fe-based alloys. MD Results show that dislocation climb and shear are two types of interaction mechanism based on the defect size. Combined MD results and machine learning, it was found that the dislocation length increased linearly with an increase in the size of the defects after the interaction. In addition, the number of atoms in the Cu-rich cluster and the reduced number of vacancies in the voids had a square relationship with the defect size where 0.85D2 is for Cu-rich cluster and 0.50D2 is for void. Furthermore, atomic-scale three-dimensional irradiation-induced defect kinetics models were developed and incorporated into the crystal plasticity finite element model (CPFEM). We also analyzed the contributions of various defects to the increase in the yield stress during CPFEM simulation. Compared with DBH model, the prediction of MD data-driven CPFEM matches better with the experimental data. Cluster contributed the most to hardening with low obstacle strength due to the higher number density compared with dislocation loops and voids. The loops also contributed to hardening; however, their contribution was smaller than that of the clusters. Although the number density and size of voids were minimized, they may have contributed because of the high obstacle strengths. This work can indeed deepen the understanding of irradiation effect in Fe-based alloys.

Objective: To investigate the characteristics of three-dimensional distribution of subchondral fracture lines on the surface of the osteonecrosis femoral head, and to discuss the underlying mechanisms that contribute to its collapse. Methods: We retrospectively analyzed computed tomography (CT) images from 75 patients (comprising a total of 77 femoral heads) diagnosed with Association Research Circulation Osseous (ARCO) stage IIIA or IIIB femoral head necrosis. The three-dimensional structures of both the femoral head and the subchondral fracture line were reconstructed and subsequently fitted into normal femoral head model. A heat map of fracture line was generated to visualize its spatial distribution across the femoral heads surface.to observe its distribution. In addition to that, the femoral head was partitioned into four zones, and the frequency of each fracture line traversing different zones was calculated and analysed. Results: Highest and lowest density of subchondral fracture lines was demonstrated in anterolateral and posterolateral zone respectively. and most sparse in posterolateral. Furthermore, the three-dimensional heat map of fracture lines highlighted their most frequent occurrence in the anterolateral area, particularly near the junction of the femoral head and neck. One fracture line may pass through multiple areas, passage frequencies for fracture lines was observed in zones I, II, III and IV for 66 times (85.7 %), 52 times (67.5 %), 25 times (32.5 %) and 46 times (59.7 %), respectively, with a significant difference between zone I and other zones (P

In this work we study the effects of different factors of dislocation loop on its obstacle strength when interacting with an edge dislocation. At first, the interaction model for dislocation and dislocation loop is established and the full and partial absorption mechanism is obtained. Then, the effect of temperature, size and burgers vector of dislocation loop are investigated. The relation between the obstacle strength and irradiation dose has been established, which bridges the irradiation source and microscale properties. Except that, the obstacle strength of C, Cr, Ni, Mn, Mo and P decorated dislocation loop is studied. Results show that the obstacle strength for dislocation loop decorated by alloy element decreases in the sequence of Cr, Ni, Mn, C, P and Mo, which could be used to help parameterize and validate crystal plasticity finite element model and therein integrated constitutive laws to enable accounting for irradiation-induced chemical segregation effects.

Irradiation defects are known to impede the dislocation motion in irradiated reactor pressure vessel (RPV) steels. However, consistent experimental studies of the respective irradiation defects and relevant theoretical studies of the interaction mechanism and hardening model are still lacking. In this study, the microstructure and irradiation-induced hardening of RPV steels are investigated using transmission electron microscopy (TEM)/energy-dispersive X-ray spectrometry (EDS) and molecular dynamics (MD) simulations. In A508-Ⅲ steel, 9R, twinned fcc, and other typical Cu-rich cluster structures are observed using TEM after the irradiation experiment. Based on the experimental results, MD simulations are performed to study the interactions between the dislocations and Cu clusters or voids. A mechanism diagram of the interaction mechanism coupling the effects of temperature and defect size is shown for both the Cu clusters and voids. A relevant hardening model is proposed based on the MD data, which is further discussed in relation to the macroscopic mechanical properties. Furthermore, the irradiation-induced hardening of the RPV steel is successfully predicted, which further demonstrates the reliability of the proposed unified hardening model.

Gastrointestinal cancer is among the most common cancers worldwide. Immune checkpoint inhibitor-based cancer immunotherapy has become an innovative approach in cancer treatment; however, its efficacy in gastrointestinal cancer is limited by the absence of infiltration of immune cells within the tumor microenvironment. Therefore, it is therefore urgent to develop a novel therapeutic drug to enhance immunotherapy. In this study, we describe a previously unreported potentiating effect of Icariside I (ICA I, GH01), the main bioactive compound isolated from the Epimedium species, on anti-tumor immune responses. Mechanistically, molecular docking and SPR assay result show that ICA I binding with TRPV4. ICA I induced intracellular Ca2+ increasing and mitochondrial DNA release by targeting TRPV4, which triggered cytosolic ox-mitoDNA release. Importantly, these intracellular ox-mitoDNA fragments were taken up by immune cells in the tumor microenvironment, which amplified the immune response. Moreover, our study shows the remarkable efficacy of sequential administration of ICA I and anti-α-PD-1 mAb in advanced tumors and provides a strong scientific rationale for recommending such a combination therapy for clinical trials. ICA I enhanced the anti-tumor effects with PD-1 inhibitors by regulating the TRPV4/Ca2+/Ox-mitoDNA/cGAS/STING axis. We expect that these findings will be translated into clinical therapies, which will benefit more patients with cancer in the near future.

Background: Non-invasive prenatal tests (NIPT) are used to screen for trisomy 21, 18, and 13. This study investigated NIPT performance and the clinical significance of its results. Methods: Pregnant women (n = 282,911) participating in a free NIPT (April 2018–December 2021) were screened for common trisomies, and the results were retrospectively analyzed. NIPT performance was evaluated by its positive predictive value (PPV), sensitivity, and specificity. Results were analyzed using number, percentage, and chi-squared/t-test analyses. Results: After NIPT screening, patients with common trisomies (n = 746) included 457 with T21, 160 with T18, and 129 with T13. Seven false negative cases were identified. High PPV (86.81 %, 56.81 %, 18.18 %), sensitivity (99.25 %, 98.33 %, 100.00 %), and specificity (99.98 %, 99.98 %, 99.97 %) values were detected for trisomy 21, 18, and 13, respectively. The PPVs of common trisomies were significantly different between pregnant women older than 35 (85.53 %, 136/159) and those aged 35 or younger (58.90 %, 311/528) (χ2 = 125.02, P = 2.20e-16). As the NIPT uptake increased from 2018 to 2021, live-born birth defect incidence decreased. Conclusion: NIPT performed well in screening for T21, T18, and T13. Our discoveries offer an important and useful guideline in laboratory and clinical genetic counseling.

With the discovery of evidence that many endocrine-disrupting chemicals (EDCs) in the environment influence human health, their toxic effects and mechanisms have become a hot topic of research. However, investigations into their endocrine-disrupting toxicity under combined binary exposure, especially the molecular mechanism of combined effects, have rarely been documented. In this study, two typical EDCs, perfluorooctanoic acid (PFOA) and 4-hydroxybenzophenone (4-HBP), were selected to examine their combined effects and molecular mechanism on MCF-7 cell proliferation at environmentally relevant exposure concentrations. We have successfully established a model to evaluate the binary combined toxic effects of endocrine disruptors, presenting combined effects in a simple and direct way. Results indicated that the combined effect changed from additive to synergistic from 1.25 × 10−8 M to 4 × 10−7 M. Metabolomics analyses suggested that exposure to PFOA and 4-HBP caused significant alterations in purine metabolism, arginine, and proline metabolism and had superimposed influences on metabolism. Enhanced combined effects were observed in glycine, serine, and threonine metabolic pathways compared to exposure to PFOS and 4-HBP alone. Additionally, the differentially expressed genes (DEGs) are primarily involved in Biological Processes, especially protein targeting the endoplasmic reticulum, and significantly impact the oxidative phosphorylation and thermogenesis-related KEGG pathway. By integrating metabolome and transcriptome analyses, PFOA and 4-HBP regulate purine metabolism, the TCA cycle, and endoplasmic reticulum protein synthesis in MCF-7 cells via mTORC1, which provides genetic material, protein, and energy for cell proliferation. Furthermore, molecular docking confirmed the ability of PFOA and 4-HBP to stably bind the estrogen receptor, indicating that they have different binding pockets. Collectively, these findings will offer new insights into understanding the mechanisms by which EDCs produce combined toxicity.

Background: The benefit of injection laryngoplasty (IL) on voice for unilateral vocal fold paralysis (UVFP) is supported increasingly in literatures, yet less is known for swallowing. Also, prevalence of patient-reported dysphagia is substantially higher than instrumental studies. This prospective study focused on swallowing outcomes, with predetermined flexible endoscopic evaluation of swallowing (FEES) protocol that simulates daily life situation. Methods: Adult patients with UVFP and aspiration receiving IL were recruited. Voice outcome measurements, as well as swallowing outcomes including Eating Assessment Tool (EAT-10) and FEES, which challenged patients with different fluid volumes: 10 mL, 20 mL, and 90 mL cup sipping were evaluated. Results: Significant improvements were demonstrated in all voice outcomes. Significant changes were also presented inEAT-10 (P

Background/objective: The literature has discussed the potential for nurturing, integrating, and optimizing physical literacy to thereby enhance quality of life. Progression could be made through the disposition of acquiring movements and engaging in physical activity, but data supporting such an argument remains limited. This cross-sectional study attempted to empirically investigate these two variables by assessing the levels of motivation and satisfaction among university students in Taiwan. The hypothesis posited a positive correlation between physical literacy and quality of life, with the mediating effects of motivation and satisfaction taken into consideration. Methods: By applying the time segregation method, participants were asked to complete a set of questionnaires at the beginning and the end of the first semester during the 2021 – 2022 academic year. The initial phase involved gathering demographic information and assessing the perceived physical literacy score. The scores for motivation, satisfaction, and quality of life were measured in the subsequent phase. SmartPLS version 3.3 was used to conduct data analysis. After ratifying the model's goodness-of-fit, partial least squares structural equation modeling was used to test the hypotheses in the research model. Results: A total of 388 students (male n = 320, female n = 68; mean age: 18.5 years) participated in this study. Moderate explanatory power was found in the relationships of perceived physical literacy to physical education satisfaction (β PPLI → PES = 0.137, t = 6.439, R2 = 0.642) and motivation (β PPLIA → SIMS = 0.511, t = 32.701, R2 = 0.607). Results then indicated that motivation is the mediator of the relationship between physical literacy and physical education satisfaction (β PPLI → SIMS → PES = 0.373, t = 4.015). Furthermore, this satisfaction mediated the relationship between physical literacy and quality of life (β PPLI → PES → QoLS = 0.070, t = 4.47). Conclusion: This study connected theoretical knowledge regarding physical literacy with practice, suggesting that ongoing physical education may nurture the habit of lifelong participation in physical activity, thus further improving quality of life.

In managing unique complexities associated with Chinese medicinal quality assessment, metabolomics serves as an innovative tool. This study proposes an analytical approach to assess differing qualities of Scrophularia ningpoensis （S. ningpoensis）Hemsl by identifying potential biomarker metabolites and their activity with the corresponding secondary metabolites. The methodology includes four steps; first, a GC-MS based metabolomics exploration of the Scrophularia ningpoensis Hemsl. Second, a multivariate statistical analysis (PCA, PLS-DA, OPLS-DA) for quality assessment and biomarker identification. Third, the application of ROC analysis and pathway analysis based on identified biomarkers. Finally, validation of the associated active ingredients by HPLC. The analysis showed distinct metabolite profiles across varying grades of S. ningpoensis Hemsl, establishing a grading dependency relationship. Select biomarkers (gluconic Acid, d-xylulose, sucrose, etc.) demonstrated robust grading performances. Further, the Pentose Phosphate Pathway, deemed as most influential in grading, was tied to the synthesis of key constituents (iridoids, phenylpropanoids). HPLC validation tests affirm a decreasing trend in harpagoside and cinnamic acid levels between first and third-grade samples. In conclusion, this GC-MS based metabolomics combined HPLC method offers a sound approach to assess and distinguish quality variations in S. ningpoensis Hemsl samples.

Kelp, the brown alga distributed in coastal areas all over the world, is also an important medicine food homology product in China. However, the levels and profiles of persistent organic pollutants (POPs) in kelp have not been thoroughly investigated to date. Polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and emerging bromine flame retardants (eBFRs) were evaluated in 41 kelp samples from the main kelp producing areas in China. The concentrations of total PCBs, PBDEs and eBFRs were in the range of 0.321–4.24 ng/g dry weight (dw), 0.255–25.5 ng/g dw and 3.00 × 10−3-47.2 ng/g dw in kelp, respectively. The pollutant pattern was dominated by decabromodiphenyl ethane (DBDPE, 13.0 ± 11.7 ng/g dw) followed in decreasing order by BDE-209 (2.74 ± 4.09 ng/g dw), CB-11 (1.32 ± 1.06 ng/g dw). The tested results showed that kelp could reflect the pollution status of PCBs, PBDEs and eBFRs, indicating the suitability of kelp as a biomonitor of these harmful substances. Finally, the data obtained was used to evaluate human non-cancer and cancer risks of PCBs and PBDEs via kelp consumption for Chinese. Though the calculated risk indices were considered acceptable according to the international standards even in the worst scenarios, the POPs levels in kelp should be monitored continuously as a good environmental indicator.

In this work, a new pyrylium derivatization-assisted liquid chromatography-mass spectrometry (LC-MS) method was developed for metabolite profiling of the glutathione anabolic pathway (GAP) in cancer tissues and cells. The pyrylium salt of 6,7-dimethoxy-3-methyl isochromenylium tetrafluoroborate (DMMIC) was used to label the amino group of metabolites, and a reductant of dithiothreitol (DTT) was employed to stabilize the thiol group. By combining DMMIC derivatization with LC-MS, it was feasible to quantify the 13 main metabolites on the GAP in complex biological samples, which had good linearity (R2 = 0.9981−0.9999), precision (interday precision of 1.6%–19.0% and intraday precision of 1.4%–19.8%) and accuracy (83.4%–115.7%). Moreover, the recovery assessments in tissues (82.5%–107.3%) and in cells (98.1%–118.9%) with GSH-13C2, 15N, and Cys-15N demonstrated the reliability of the method in detecting tissues and cells. Following a methodological evaluation, the method was applied successfully to investigate difference in the GAP between the carcinoma and para-carcinoma tissues of esophageal squamous cell carcinoma (ESCC) and the effect of p-hydroxycinnamaldehyde (CMSP) on the GAP in KYSE-150 esophageal cancer cells. The results demonstrate that the developed method provides a promising new tool to elucidate the roles of GAP in physiological and pathological processes, which can contribute to research on drugs and diseases.

A thermal-mechanical control process (TMCP) followed by tempering at 600 °C was applied to produce 420 MPa grade high strength low alloy (HSLA) steel heavy plates. The microstructure and mechanical properties through the thickness were analyzed using various techniques including optical microscopy (OM), scanning electron microscopy (SEM), transmission electron microscopy (TEM), electron back-scattered diffraction (EBSD), tensile and impact tests. Microscopy analyses showed that a fine-grained structure with an average grain size of 6–10 μm could be obtained by TMCP. After subsequent tempering, the microstructure near the surface of the plate was dominated by bainite, while the microstructure of the core was mainly characterized by aggregated carbides and ferrite. In addition, the density of high-angle grain boundaries (HAGB) on the surface was significantly higher than that in the core. Tensile tests showed a decrease in both yield and tensile strengths from 530.1 and 626.9 MPa on the surface to 384.3 and 496.7 MPa in the core, respectively. The contribution of different strengthening mechanisms to the variations in strengths along the thickness was clarified. In addition, the deformation of ferrite and the initiation of micro-voids during tensile tests were also analyzed.

The challenges commonly associated with conventional high pressure die casting (HPDC) have led to increased interest in semi-solid metal (SSM) forming processes. In the present study, semi-solid slurries of A356 alloy prepared by the Swirled Enthalpy Equilibration Device (SEED) process were used for manufacturing components with complex shape by using a high pressure die casting machine. The segregation phenomenon and the effect of heat treatment on the microstructure evolution and mechanical properties were investigated. The results showed that the alloy consists of primary spherical α-Al grains, secondary solidified α-Al grains, eutectic Si, iron-rich intermetallic phases and low porosities. The microstructural investigations revealed that the eutectic Si particles underwent fragmentation, spheroidization and coarsening with increasing solution temperature. Furthermore, the solution treatment results in the dissolution of the π-Al8FeMg3Si6 phase and the growth of the β-Al5FeSi phase. The hardening peaks at 170 °C could be obtained with ageing for 5 h. Due to both solution and precipitation strengthenings, the yield strength, ultimate tensile strength and hardness of A356 alloy after heat treatment increase significantly compared to those in the as-rheocast state: they reach 266 MPa, 343 MPa and 110 HV0.2, respectively. The analysis of fracture surfaces of rheo-HPDC samples in both the as-rheocast and the heat-treated states revealed a mixed mechanism of dimples and quasi-cleavage. The microstructure inside the part was found to be quasi-homogeneous while the segregation phenomenon in different zones of the part is affected by die geometry during the filling process. The results imply that the SEED-HPDC process has the potential to be industrialized by implementing appropriate heat treatments for producing complex components with good mechanical properties.

This work elucidates the photoelectrochemical (PEC) sensing of melatonin employing graphene oxide nanoribbons (GONRs) synthesized through a microwave-assisted method. GONRs served as electrocatalysts for screen-printed carbon electrodes (SPCE) to facilitate melatonin detection. We incorporated both a light-emitting diode (LED) and a solar simulator as light sources for PEC evaluations. Cyclic voltammetry revealed that the faradaic currents corresponding to melatonin oxidation on GONRs-modified SPCE were amplified under both LED and simulated solar light irradiation. Notably, the GONR (150 W) registered the most pronounced enhancement in the photo-assisted faradaic current and the highest conversion efficiency. Employing the solar simulator, certain thermal factor ratios concerning conversion efficiencies surpassed 50.0% at light intensities of both 80 mW/cm2 and 100 mW/cm2. Conversely, with the LED source, the thermal contribution remained below 15.0% of the total PEC faradaic current. We posit that obtaining conversion efficiencies devoid of thermal influences is pivotal for deepening our comprehension of PEC biosensing mechanisms.

Androgen receptor (AR) signaling is essential in prostate cancer treatment. For many years, androgen deprivation therapy (ADT) has been primarily applied to manage advanced prostate cancer. However, most individuals with metastatic hormone-sensitive prostate cancer (mHSPC) administered ADT alone are at risk of developing metastatic castration-resistant prostate cancer (mCRPC) in less than two years. New approaches employing novel AR inhibitors (ARi) as intensified upfront systemic treatment in mHSPC have recently demonstrated substantial benefits in delaying disease progression and prolonging overall survival. Administration of novel ARi has become the new standard of care in mHSPC. The new landscape simultaneously makes treatment choice more challenging. This review provides comprehensive data on molecular structure, pharmaceutical properties, and efficacy and safety profiles reported by pivotal clinical trials. We also discuss future directions with ongoing Phase III trials of novel ARi in mHSPC. Considering these biological and clinical insights, this review aimed to provide a comprehensive understanding of differences in the development and applications of novel ARi for mHSPC, which may be helpful in designing strategies for first-line treatment choices.

Purpose: Mineralocorticoid receptor antagonists are the first-line treatment for bilateral adrenal hyperplasia (BAH) with primary aldosteronism (PA), while unilateral adrenalectomy is the standard treatment for aldosterone-producing adenoma (APA). In this study, we investigated the outcomes of patients with BAH after unilateral adrenalectomy and compared them with those of patients with APA. Methods: From January 2010 to November 2018, 102 patients with a diagnosis of PA confirmed by adrenal vein sampling (AVS) and available NP-59 scans were enrolled. All patients underwent unilateral adrenalectomy based on the lateralization test results. We prospectively collected the clinical parameters over 12 months and compared the outcomes of BAH and APA. Results: A total of 102 patients were enrolled in this study: 20 (19.6%) had BAH and 82 (80.4%) had APA. Significant improvements in serum aldosterone-renin ratio (ARR), potassium level, and reduction of antihypertensive drugs were observed in both groups at 12 months after surgery (all p

Background/purpose: A challenge that arises with periodontal regeneration surgery has been associated with the future development of periodontal regeneration membrane to prevent gingiva and fibroblasts invade the wound and allow alveolar bone successfully regenerated. Materials and methods: Chitosan (CS) has the advantages of non-toxicity, biodegradation, biocompatibility, and has been widely used in wound dressings. A flexible film was made using polyvinyl alcohol (PVA) blending CS based thermosensitive hydrogel. Results: The proposed 2% PVA/CS hydrogel has the highest swelling ratio about 720% after 60 min incubation and keeps its area after 10 min incubation for surgery suture. The elastic modulus of 0%, 1%, 2%, and 4% PVA/CS hydrogel were 7.75 ± 1.96, 0.91 ± 0.16, 0.75 ± 0.21, and 0.37 ± 0.06 MPa, respectively. The maximum strain of 2% PVA/CS hydrogel was 101.00 ± 28.03 (%). After 8 weeks biodegradation, the remain weight of 2% PVA/CS hydrogel was 71.36 ± 0.79 (%). Conclusion: In vitro cytotoxicity tests were performed and demonstrated PVA/CS hydrogel significantly improving cell proliferation. This study realized a promising flexible film for periodontal regeneration membrane that can prevent the rapid growth of fibroblasts to invade the wound and be used for periodontal regeneration surgery.

As unsafe food production poses global health threats, especially in developing countries, food safety detection always significantly impacts all fields of the food industry, such as production, processing, transportation, storage, and consumption. Many classical food safety detecting methods have been widely used to provide accurate, sensitive, and reliable analytical characteristics, while they rely on clean laboratories, bulky setups, trained personnel, and long-time detection. Because of those conditions, they are not suitable for on-site food safety detecting applications. To solve this problem, various food safety detecting approaches relying on field-portable devices and field-operable techniques have been designed and successfully used, indicating that they are potentially ideal solutions for on-site applications. This review summarizes the progress on on-site food safety detecting approaches and applications for various risk factors, including bacteria, parasites, viruses, toxins, pesticide and veterinary drug residues, illegal food additives, restricted food ingredients, and heavy metals. It outlines recent advances in field-portable devices and field-operable techniques that provide conditions for on-site food safety detection. Recommended on-site food safety detecting approaches for different food safety risk factors are comprehensively suggested considering detecting feasibility, accuracy, and speed. These approaches reveal an attractive and promising route for future practical food safety detecting applications with the merits of portable devices, simple user-friendly operation, and rapid on-site detection. This review further addresses current challenges, and finally discusses future trends and strategies that could be employed in on-site food safety detection.

Introduction: Lots of research has revealed that vascular dementia (VD), which is closely related to the metabolic disorders of intestinal microbiota, can be treated through traditional Chinese drug by regulating the brain-gut-microbiome axis. However, the specific interaction between VD and intestinal microflora, as well as the mechanism of Wuzang Wenyang Huayu Tang (WWHT) in treating VD by regulating the brain-gut-microbiome axi remains unknown on the whole and needs to be further studied. Objectives: To explore the effect of WWHT on the learning and memory ability of rats with VD based on brain-gut-microbiome axis. Methods: In this study, taking the specific pathogen-free (SPF) SD rats as the subjects, a vascular dementia rat model was created by using the two-vessel occlusion model (2-VO). The subjects were divided into six groups, namely control group, sham group, VD model group, the piracetam group, the WWHT group, and the WWHT combined with piracetam (WCP) group. After 22 days of the gavage administration method, the Morris water maze experiment was adopted to determine the learning and memory abilities of each group through the water maze, observe the effects of hematoxylin and eosin (HE) staining and transmission electron microscopy in the hippocampal area of each group, and analyze the relevant proteins in the whole brain by Western Blot (WB). In addition, the feces of each group were collected and analyzed by fecal metabolomics combined with 16S rRNA gene sequencing to explore the interaction between VD and intestinal microbiota. Results: Through Morris water maze experiment, it was found that the learning and memory ability of VD rats in WWHT, piracetam and WCP groups was improved. The morphology of hippocampal neuron cells were improved in the WWHT group and the number of hippocampal neuron cells were increased in the VD rats by HE. By observing the ultrastructure of hippocampal cells, it can be found that the VD model group showed cell membrane edema and large organelle lysis. The ultrastructure of the hippocampus of all the administered groups was improved. In terms of the effect on the expression levels of related proteins in the whole brain of rats, compared with the VD model group, the expression levels of Caspase-3 protein decreased in all groups after drug administration. The protein expression levels of APG5L/ATG5, Beclin-1 and LC3A/B were upregulated, indicating that the drug administration group could regulate cellular autophagy in the whole brain to further protect brain tissue. Fecal metabolite profiles revealed 27 different metabolites related to VD. These metabolites are mainly involved in related metabolic pathways, such as vitamin B metabolism, purine metabolism, pyrimidine metabolism, and histidine metabolism. Further analysis of the gut microbiota by 16S rRNA gene sequencing data showed that WWHT-treated VD rats were different in gut microbiota composition. Discussion: Through the effect of brain-gut-microbiome axis, WWHT regulates the metabolism of vitamin B6 and tryptophan in VD rats, which can improve the intestinal microbiota of VD rats and regulate autophagy in the brain to improve cell morphology in the hippocampus, thus increasing the number of hippocampal cells to protect hippocampal neuron cells2510100, and finally improving the learning and memory ability of VD rats.

Alkali-treated titanium and its alloys (with or without heat treatment) have been paid more attention in the biomaterial field for the formation of a nanoporous layer that can induce apatite deposition and improve bone-implant integration. In this work, a hierarchical micro-nano structure was fabricated by alkali treatment and subsequent induction heating at different temperatures. The surface morphology, phase composition, microstructure, and elemental binding state were investigated using scanning electron microscopy (SEM), X-ray diffractometer (XRD), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS), respectively. As the induction heating temperature increases, the porous structure of the outmost sodium titanate layer is maintained with increased anatase TiO2 and decreased wetting angle from 21.8° to 11.8°. At a relatively high temperature (700 °C), the composite layer is composed of a porous sodium titanate layer with a thickness of around 1 μm and a titanium oxide layer of about 2 μm thickness with nanopores. Importantly, the amorphous structure with the oxygen vacancy that exists on the sample surface is conducive to apatite deposition. The assessment of the in-vitro bioactivity performed in 1.5 simulated body fluid shows that the ability to induce apatite deposition increases with the increasing induction heating temperature from 500 to 700 °C. These results are helpful to understand the microstructure of the alkali and induction heating treated titanium that may be responsible for its bioactivity.

Zinc (Zn) and its alloys are considered as promising biodegradable metals due to its suitable degradability and important physiological functions. However, in the process of degradation, excessive release of Zn ions (Zn2+) will significantly affect the cytocompatibility and antibacterial properties. Surface modification technology can not only control the corrosion behavior of biodegradable metals but also improve its biocompatibility and antibacterial properties according to clinical requirements. In this study, an in-situ hopeite (HP, Zn3(PO4)2·4H2O) coating was prepared on Zn alloy by phosphate chemical conversion (PCC) method using Zn2+ provided by self-corrosion of the substrates. And the effect of phosphating time on the microstructure, phase composition, corrosion resistance, and wettability of HP coatings was investigated. The results showed that a complete HP coating was formed on the Zn alloy after reaction for 1 min, even if Zn2+ were supplied by self-corrosion without an additional Zn source. It also revealed that the reaction time had a marked impact on the morphologies and microstructures of the HP coating. The electrochemical test results proved that the prepared HP coatings had obvious protection on the Zn alloy and could regulate the corrosion rate of the substrate. Meanwhile, the Zn alloy modified by the PCC method also possessed excellent hydrophilicity. These primary findings might support new opportunities in the exploration of controllable coatings on biomedical Zn alloys.

Core-shell microspheres have attracted widespread attention in the field of drug delivery due to their special morphology and excellent surface properties. However, the preparation of the core–shell microspheres composed of hydroxyapatite (HA) have been rarely reported. In this paper, porous HA core–shell microspheres were prepared through a one-step hydrothermal method by using sodium trimetaphosphate (STMP) as the phosphorus source. SEM and TEM observations showed that the prepared porous HA core–shell microspheres were composed of a porous shell and a solid core, with a gap between the core and the shell. These microspheres bear uniform size and identical structure. With the increase of the hydrothermal time, the solid microspheres transformed to porous core–shell microspheres with the simultaneous transformation of their phase from amorphous calcium phosphate (ACP) to HA. The possible formation mechanism is proposed, providing inspiration for the design of porous HA core–shell microspheres and their potential biological applications.

Objective: Decision aids have been developed to help prospective parents make informed, shared decisions about medical tests, but these options are rapidly changing. This study aimed to identify and evaluate publicly available decision aids written in English for prospective parents seeking prenatal test information. Methods: A systematic review process was followed using 3 sources: known decision aid repositories, fetal medicine organisations and Google. The search, screening process, quality assessment, and data extraction was performed by two independent researchers. The quality assessment of the decision aids was based on the International Patient Decision Aids Standards (IPDAS v.4.0). Results: We identified 13 decision aids, which varied in the screening and diagnostic tests that they discussed. No decision aid met all the IPDAS v.4.0. criteria and no decision aid reported updated risk of miscarriage for amniocentesis and chorionic villus sampling (CVS). There was a lack of decision aids for some common decisions in the prenatal context. Conclusion: We identified outdated content in current prenatal decision aids. The findings will inform healthcare professionals of the quality of current prenatal decision aids, which may facilitate their patients’ informed decision-making about prenatal tests. Innovation: Considerations for improving future decision aids are outlined.

Background: Maternal Toxoplasma gondii (T. gondii) infection during pregnancy has been associated with various mental illnesses in the offspring. Ginsenoside Rh2 (GRh2) is a major bioactive compound obtained from ginseng that has an anti-T. gondii effect and attenuates microglial activation through toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway. GRh2 also alleviated tumor-associated or lipopolysaccharide-induced depression. However, the effects and potential mechanisms of GRh2 on depression-like behavior in mouse offspring caused by maternal T. gondii infection during pregnancy have not been investigated. Methods: We examined GRh2 effects on the depression-like behavior in mouse offspring, caused by maternal T. gondii infection during pregnancy, by measuring depression-like behaviors and assaying parameters at the neuronal and molecular level. Results: We showed that GRh2 significantly improved behavioral measures: sucrose consumption, forced swim time and tail suspended immobility time of their offspring. These corresponded with increased tissue concentrations of 5-hydroxytryptamine and dopamine, and attenuated indoleamine 2,3-dioxygenase or enhanced tyrosine hydroxylase expression in the prefrontal cortex. GRh2 ameliorated neuronal damage in the prefrontal cortex. Molecular docking results revealed that GRh2 binds strongly to both TLR4 and high mobility group box 1 (HMGB1). Conclusion: This study demonstrated that GRh2 ameliorated the depression-like behavior in mouse offspring of maternal T. gondii infection during pregnancy by attenuating the excessive activation of microglia and neuroinflammation through the HMGB1/TLR4/NF-κB signaling pathway. It suggests that GRh2 could be considered a potential therapy in preventing and treating psychiatric disorders in the offspring mice of mothers with prenatal exposure to T. gondii infection.

Purpose: In advanced or high-grade prostate cancer (PCa), prostate-specific antigen (PSA) is usually elevated, however, some patients may present with low initial PSA (iPSA) levels. The objective of this study was to evaluate whether different iPSA levels were associated with dissimilar clinical outcomes among men with high-grade PCa and advanced disease after robot-assisted laparoscopic radical prostatectomy (RaLRP). Methods: This study enrolled 69 PCa patients with initial Gleason score ≥8 and pathologic T-stage ≥3a from April 2012 to December 2018. Patients were stratified into 3 groups based on iPSA levels at diagnosis:

The effect of nano-scaled Si3N4 particles on the microstructure, mechanical and electrochemical behavior of hopeite (Zn3(PO4)2·4H2O) conversion coating on pure titanium was investigated. Different concentrations of nanoparticles were dispersed into the phosphating bath to incorporate the process of coating deposition. The XRD results demonstrated that nano-Si3N4 were doped into the coatings without any decomposition or reaction with the hopeite phase. A finer and denser microstructure of the composite coating could be obtained at the addition of 0.5 g/L Si3N4 in comparison with the pure hopeite coating. Moreover, the composite coating presented a higher bonding strength and corrosion resistance related to the refinement of microstructure and filling of the embedded nanoparticles. It is suggested that the incorporation of nano-Si3N4 particles in conversion coating is a promising approach for performance optimization.

Objective: Fatigue, a painful and unpleasant subjective experience, is common in perimenopausal women. Therefore, an effective tool to evaluate the fatigue-precipitating factor is important for perimenopausal women prone to fatigue syndrome. Materials and methods: This study was surveyed by short-term perimenopausal fatigue scale. The enrollment period was from November 2019 to January 2020. The subjects were perimenopausal women prone to perimenopausal fatigue. The differences between the fatigue-precipitating factors and the degrees of fatigue and disturbance were determined by one-way ANOVA and t test. Results: A total of 220 perimenopausal women with mean age of 51.3 years were included. Among these, 64.1% did not have a habit of regular exercise and 55.5% had chronic diseases. Fatigue syndrome was found in 64.1% of subjects, who were mainly presented by shoulder and neck pain and sleep problems. There were significant differences between “perimenopausal fatigue” and “duration” (p

Atrazine (ATZ) is a widely used herbicide worldwide and is a long-suspected endocrine-disrupting chemical. However, most endocrine-disrupting toxicity studies on ATZ have been based on animal models and those investigating inner mechanisms have only focused on a few genes. Therefore, the possible link between ATZ and endocrine-disrupting toxicity is still unclear. In this study, multi-omics and molecular biology techniques were used to elucidate the possible molecular mechanisms underlying the effect of ATZ exposure on MCF-7 proliferation at environmentally relevant concentrations. Our study is the first report on ATZ-induced one carbon pool by folate metabolic disorder in MCF-7 cells. A concentration of 1 μM ATZ yielded the highest cell viability and was selected for further mechanistic studies. A total of 34 significantly changed metabolites were identified based on metabolomic analysis, including vitamins, amino acids, fatty acids, and corresponding derivatives. Folate and pyridoxal have potential as biomarkers of ATZ exposure. One carbon pool by folate metabolic pathway was identified based on metabolic pathway analysis of the significantly altered pathways. Moreover, FTCD and MTHFD related to this pathway were further identified based on transcriptomic analysis and protein assays. Folate and different forms of 5,6,7,8-tetrahydrofolate, which participate in purine synthesis and associate with methyl groups (SOPC, arachidonic acid, and L-tryptophan) in one carbon pool by the folate metabolic pathway, potentially promote MCF-7 cell proliferation. These findings on the key metabolites and regulation of the related differentially expressed genes in folate metabolism will shed light on the mechanism of MCF-7 cell proliferation after ATZ exposure. Overall, this study provides new insights into the mechanistic understanding of toxicity caused by endocrine-disrupting chemicals.

Particulate matter (PM) contributes to air pollution and primarily originates from unregulated industrial emissions and seasonal natural dust emissions. Fucoxanthin (Fx) is a marine natural pigment from brown macroalgae that has been shown to have various beneficial effects on health. However, the effects of Fx on PM-induced toxicities in cells and animals have not been assessed. In this study, we investigated the anti-inflammatory potential of the Fx-rich fraction (FxRF) of Sargassum fusiformis against PM-mediated inflammatory responses. The FxRF composition was analyzed by rapid-resolution liquid chromatography mass spectrometry. Fx and other main pigments were identified. FxRF attenuated the production of inflammatory components, including prostaglandin E2 (PGE2), cyclooxygenase-2, interleukin (IL)-1β, and IL-6 from PM-exposed HaCaT keratinocytes. PM exposure also reduced the levels of nitric oxide (NO), tumor necrosis factor-α, inducible nitric oxide synthase (iNOS), and PGE2 in PM-exposed RAW264.7 macrophages. Additionally, the culture medium from PM-exposed HaCaT cells induced upregulation of NO, iNOS, PGE2, and pro-inflammatory cytokines in RAW264.7 macrophages. FxRF also significantly decreased the expression levels of factors involved in inflammatory responses, such as NO, reactive oxygen species, and cell death, in PM-exposed zebrafish embryos. These results demonstrated the potential protective effects of FxRF against PM-induced inflammation both in vitro and in a zebrafish model.

Background/Purpose: The inflammatory milieu has been firmly established to affect cancer progression. However, the connection between natural killer (NK) cells and prostate cancer (PCa) has not been elucidated. Methods: Prospective data on NK cell activity (NKA) and NK cell subset distribution patterns were evaluated from 51 patients treated with robot-assisted laparoscopic radical prostatectomy. Whole-blood samples were collected from patients preoperatively and 4–6 weeks postoperatively. The samples were subjected to NKA tests, NK cell number counts, determination of the NKG2D (activating receptor of NK cells), NKG2A (inhibiting receptor), and other surface markers. All the analyses were compared to the clinicopathological characteristics of patients. NKA was estimated by measuring interferon-γ (IFN-γ) levels after stimulation of the peripheral blood with PROMOCA™, which specifically stimulates the release of IFN-γ from NK cells. Results: NKA was lower in patients with PCa than in healthy participants (484.66 vs. 1550 pg/mL). A paired comparison revealed significantly higher NKA postoperatively than preoperatively (1054 vs. 484.66 pg/mL; p = 0.011). Patients with negative surgical margins exhibited significantly higher postoperative NKA and NKA ratio (postoperative NKA/preoperative NKA) than those with positive margins (557 vs. 1921 pg/mL, p

Obese sarcopenia is associated with palmitic acid (PA), an abundant circulating saturated fatty acid. This study examined a non-cytotoxic concentration of PA to provide mechanistic insights into PA-impaired skeletal myogenesis and potential medicinal and dietary interventions through edible brown seaweed, Ishige okamurae (IO). C2C12 cells were examined for myogenic markers, adipogenic factors, and regenerative capacity through growth regulators against PA interference to assess IO and purified diphloroethohydoxycarmalol (DPHC) as potential treatments. Both IO and DPHC improved myogenic marker (myogenin, MyoD, and MyHC) levels. PA down-regulated myogenic markers while improving adipogenic factors (PPARγ, c/EBPα, A-FABP), DPHC significantly arbitrated the negative effects. DPHC treatment also improved phosphorylation of the growth regulatory PI3K/Akt/mTOR axis over the adverse effects of PA. The results of this study suggested regulatory mechanisms through which the bioactive components IO and DPHC based on the sustainable utilization of I. okamurae inhibited the PA-induced impairment of skeletal myogenesis.

A novel coating method of transforming scholzite (SZ, CaZn2(PO4)2·2H2O) into hydroxyapatite (HA, Ca10(PO4)6(OH)2) coating on the surface of titanium (Ti) has been presented. It deposited a primary SZ coating through a phosphate chemical conversion (PCC) technology, and then transformed it to the HA coating via calcium (Ca) chelating. FE-SEM and XRD results proved that a nanostructured HA coating with a cauliflower-like shape and without zinc (Zn) element doping could be obtained from the primary petal-like SZ coating. It suggests that SZ may act as a simple and effective intermediate for HA precipitation. The electrochemical impedance spectroscopy (EIS) test was employed to evaluate the corrosion behavior of the coated samples in simulated body fluid (SBF). The results showed that the HA-coated sample obtained by Ca chelating post-treatment exhibited improved barrier performance compared with the primary SZ-coated one.

Purpose: The purpose of this study was to assess the amount of variance in the coping strategies of patients with brain tumors that could be accounted for by resilience. Methods: This cross-sectional survey involved 95 patients who had experienced surgical, chemotherapy, or radiotherapy therapies for their brain tumors at least 1 month before data collection. The investigator collected data using the scales of the Ways of Coping Checklist-Revised and Resilience Scale. Data were analyzed using descriptive statistics, t tests, analysis of variance, Pearson product–moment correlation, and hierarchical multiple regression. Results: The results revealed that resilience was significantly positively associated with patients' problem-focused coping (r = .65, p

Summary: CD4 T cells are essential for immunity to tuberculosis because they produce cytokines, including interferon-γ. Whether CD4 T cells act as “helper” cells to promote optimal CD8 T cell responses during Mycobacterium tuberculosis is unknown. Using two independent models, we show that CD4 T cell help enhances CD8 effector functions and prevents CD8 T cell exhaustion. We demonstrate synergy between CD4 and CD8 T cells in promoting the survival of infected mice. Purified helped, but not helpless, CD8 T cells efficiently restrict intracellular bacterial growth in vitro. Thus, CD4 T cell help plays an essential role in generating protective CD8 T cell responses against M. tuberculosis infection in vitro and in vivo. We infer vaccines that elicit both CD4 and CD8 T cells are more likely to be successful than vaccines that elicit only CD4 or CD8 T cells.

Abnormalities in angiogenesis that are associated with diabetes may contribute to vascular complications and result in disabilities and death. Furthermore, an imbalance in angiogenesis in different tissues, including the retina and kidney, can play a role in the pathogenesis of diabetic microvascular complications. Phlorotannins, such as phloroglucinol (PG) and dieckol (DK), which are found in Ecklonia cava exhibit antioxidant and anti-inflammatory activities that improve endothelial function in hypertension. However, reports on the effects of these compounds on diabetes-induced angiogenesis in vivo and in vitro are scarce. In this study, we assessed the antiangiogenic effects of PG and DK on endothelial cells treated with a high concentration of glucose to mimic angiogenesis. In addition, we sought to determine the effects of these compounds on cell proliferation, cell migration, and capillary formation. In silico docking of PG and DK into VEGFR-2 revealed their potential as therapeutic agents against angiogenesis. Further, both compounds were identified to inhibit the formation of the retinal vessel in transgenic zebrafish (flk:EGFP) embryos under high glucose conditions. These findings suggested that PG and DK derived from E. cava are potential inhibitors of angiogenesis in diabetic vascular complications and could, therefore, be used to develop angiogenic agents.

Background: Pleural fibrosis is defined as excessive depositions of matrix components that result in pleural tissue architecture destruction and dysfunction. In severe cases, the progression of pleural fibrosis leads to lung entrapment, resulting in dyspnea and respiratory failure. However, the mechanism of pleural fibrosis is poorly understood. Methods: miR-4739 levels were detected by miRNA array and real-time PCR. Real-time PCR, western blotting and immunofluorescence were used to identify the expression profile of indicators related to fibrosis. Target gene of miR-4739 and promoter activity assay was measured by using dual-luciferase reporter assay system. In vivo, pleural fibrosis was evaluated by Masson staining and miR-4739 level was detected by In situ hybridization histochemistry. Findings: We found that bleomycin induced up-regulation of miR-4739 in pleural mesothelial cells (PMCs). Over-regulated miR-4739 mediated mesothelial-mesenchymal transition and increased collagen-I synthesis in PMCs. Investigation on the clinical specimens revealed that high levels of miR-4739 and low levels of bone morphogenetic protein 7 (BMP-7) associated with pleural fibrosis in patients. Then we next identified that miR-4739 targeted and down-regulated BMP-7 which further resulted in unbalance between Smad1/5/9 and Smad2/3 signaling. Lastly, in vivo studies revealed that miR-4739 over-expression induced pleural fibrosis, and exogenous BMP-7 prevented pleural fibrosis in mice. Interpretation: Our data indicated that miR-4739 targets BMP-7 which mediates pleural fibrosis. The miR-4739/BMP-7 axis is a promising therapeutic target for the disease. Fund: The National Natural Science Foundation of China. Keywords: Pleural fibrosis, Pleural mesothelial cells (PMCs), miR-4739, BMP-7, Mesothelial-mesenchymal transition (MMT)

Background/Purpose: Prostate specific antigen (PSA) with low specificity that causes unnecessary prostate biopsies increases clinical morbidities, psychological stress, and medical expenses. We aimed to test the accuracy and cutoff value of Prostate Health Index (PHI) in men for prostate cancer detection. Methods: We prospectively enrolled 213 men who underwent prostate biopsy with PSA≦10 ng/ml or abnormal findings on digital rectal examination. Total PSA (tPSA), free PSA (fPSA) and p2PSA levels were measured by serum samples before prostate biopsy. PHI was calculated as (p2PSA/fPSA) × √tPSA. Multivariable logistic regression analyses were used to predict the risk of cancer and detect clinically significant prostate cancer. Results: 33 (27.0%) patients were confirmed with the diagnoses of prostate cancer by prostate biopsy. The levels of p2PSA, %p2PSA, and PHI showed statistically significant differences between prostate cancer patients and non-cancer patients. %p2PSA and PHI had the highest area under the receiver operating characteristic curve (AUC) of 0.723 and 0.772 (both p

In this work, we study how to minimize the average system delay in a cloud computing center with heterogeneous servers, where each server may have a different average service rate. We consider M ∕ M i ∕ C ∕ K with a single server threshold and double congestion thresholds. The analytical models and performance measures are derived for the systems considered. The effect of the average arrival rate on performance measures is studied. It is shown that M ∕ M i ∕ C ∕ K with a single server threshold and double congestion thresholds outperforms M ∕ M i ∕ C ∕ K in terms of the average system delay. Finally, a computer simulation is written to verify the accuracy of the analytical results. Keywords: Average arrival rate, Average system delay, Cloud computing center, Heterogeneous server

The health crisis caused by the new coronavirus (SARS-CoV-2) exposes latent social tensions arising from the process of globalization. The battle for the history of the responsibility for the crisis opens new fronts in which, thanks to social media, the public seems to be actively engaged. The first case of coronavirus in Brazil was confirmed in February, followed by a rapid increase in cases, news, and discourses on social media. Against this background, this article examines the following research question: what themes and sentiments are evoked in tweets posted in Portuguese linking the COVID-19 pandemic to China? We conducted a time series study of tweets posted during the period 19 March to April 3, 2020, retrieving 1.6 million tweets. The data was filtered in three stages and thematic and sentiment analysis was performed across the data set. The findings show that the most frequently occurring themes were the “Chinese virus”, “virus from China”, use of chloroquine, cure, the press and quality of information, dictatorship, China, Bolsonaro, and communism. The content of the tweets on these themes clearly reveals user sentiment, with a predominance of negative sentiments (fear, sadness and anger) and low proportion of sentiments in the category trust. The themes and sentiments evoked in the tweets reveal elements that characterize the current context of political polarization in Brazil and its effects on Twitter users’ understanding of the COVID-19 pandemic.

Background: UPEC can internalize clonally in prostate to form biofilm-like intracellular bacterial communities (IBCs) for recurrent or chronic infection. We previously indicated that the exposure of prostate cells to testosterone could suppress UPEC invasion and their persistent survival within cells by effectively inhibiting the JAK/STAT1 signaling pathway. However, the regulatory mechanism by which testosterone affects UPEC-induced prostatitis via STAT3, another latent transcription factor signaling pathway is still unclear. The present study aimed to clarify the role of STAT3 in the process of UPEC-induced inflammation and colonization in prostate epithelial cells. Methods: The effects of testosterone-mediated inhibition were compared between the prostatitis by different UPEC strains (CFT073 and J96) through the specific GFP-UPEC-infected prostate cell model. Fluorescence microscopy was used for UPEC IBCs detection and quantifying, and Flow cytometry, RT-PCR and western blotting were used for analyzing related gene and protein expressions. Pretreatment of JAK and STAT3 inhibitors were also applied to verify the regulation of transduction pathway in testosterone-mediated anti-UPEC infection. Results: This study revealed that testosterone effectively suppresses UPEC infection and IBC formation in prostate cells through the JAK/STAT3 pathway. The results show that CFT073 and J96 UPEC infection rates and colony numbers were dose-dependently reduced in RWPE-1 cells pretreated with 5 and 20 μg/mL testosterone at 0 and 24 h post-infection. Further, testosterone reduced the amounts of UPEC infecting and surviving within the prostate cells, as well as suppressed the size of IBCs formed. We demonstrated that pretreating testosterone effectively inhibited UPEC infection along with dose-dependent suppression of STAT3 and the phosphorylated-STAT3 expression in prostate cells, especially in 24 h J96 UPEC infected groups. The STAT inhibitor, SOCS3 also up-regulated at the same time. In addition, we pretreated the JAK1 or STAT3 inhibitor with testosterone to block the signaling transduction before CFT073 and J96 UPEC infection, and found the significant restoring in both the sizes of IBCs and bacterial numbers in RWPE-1 cells. Therefore, our results suggest that the suppression of STAT3 by testosterone treatment attenuate UPEC growing within IBCs and interfere with their infection to prostate cells. Conclusions: Overall, our study demonstrates that testosterone suppresses the initial infection of prostate epithelial cells by UPEC and reduces the survival of UPEC within IBCs after infection. These results indicate a critical role for STAT3 in facilitating UPEC infection and persistence, and its participation in driving testosterone-suppressive responses in prostate epithelial cells. In conclusion, this study suggests that testosterone may be beneficial in treating clinically recurrent UPEC infections and, thus, the persistent recurrence of prostatic inflammation.

Agropyron cristatum, a wild relative of common wheat (Triticum aestivum L.), provides many desirable genetic resources for wheat improvement, such as tolerance to cold, drought, and disease. To transfer and utilize these desirable genes, in this study, two wheat-A. cristatum derivatives II-13 and II-23 were identified and analyzed. We found that the number of root tip cell chromosomes was 44 in both II-13 and II-23, but there were four and six P genome chromosomes in II-13 and II-23, respectively, based on genomic in situ hybridization (GISH). The chromosome configurations of II-13 and II-23 were both 2n=22II by the meiotic analysis of pollen mother cells (PMCs) at metaphase I, indicating that there were two and three pairs of P chromosomes in II-13 and II-23, respectively. Notably, wheat chromosome 7D was absent in derivative line II-13 while II-23 lacked chromosomes 4B and 7A based on SSR analysis combining fluorescence in situ hybridization (FISH) analysis with pAs1 and pSc119.2 as probes. Chromosomes 2P and 7P were detected in both II-13 and II-23. Another pair of P genome chromosomes in II-23 was determined to be 4P based on expressed-sequences tags-sequence tagged sites (EST-STS) markers specific to A. cristatum and FISH with probes pAcTRT1 and pAcpCR2. Overall, these results suggest that II-13 was a 7P (7D) substitution line with one pair of additional 2P chromosomes and II-23 was a multiple 4P (4B), 7P (7A) substitution line with one pair of additional 2P chromosomes. Moreover, we obtained six alien disomic addition lines and five alien disomic substitution lines by backcrossing. These new materials will allow desirable genes from A. cristatum to be used in common wheat.

Accumulated genetic evidences indicate that the contactin associated protein-like (CNTNAP) family is implicated in autism spectrum disorders (ASD). In this study, we identified genetic mutations in the CNTNAP3 gene from Chinese Han ASD cohorts and Simons Simplex Collections. We found that CNTNAP3 interacted with synaptic adhesion proteins Neuroligin1 and Neuroligin2, as well as scaffolding proteins PSD95 and Gephyrin. Significantly, we found that CNTNAP3 played an opposite role in controlling the development of excitatory and inhibitory synapses in vitro and in vivo, in which ASD mutants exhibited loss-of-function effects. In this study, we showed that the male Cntnap3-null mice exhibited deficits in social interaction， spatial learning and prominent repetitive behaviors. These evidences elucidate the pivotal role of CNTNAP3 in synapse development and social behaviors, providing mechanistic insights into ASD.

Accumulating evidence suggests that modulating the gut microbiota may be a potential method for treating alcohol dependence. Galacto-oligosaccharides (GOS) are a traditional prebiotic that positively affects the host’s gut microbiota. In this study, using a rat model of chronic alcohol dependence, we analysed the impact of GOS on possible alterations in the gut microbiota and intestinal permeability. Through 16S rRNA sequencing, we found that GOS markedly changed the gut microbiota composition and resolved microbiome dysbiosis induced by chronic alcohol consumption. Moreover, compared with alcohol dependence, GOS supplementation after alcohol detoxification downregulated alcohol withdrawal scores and decreased diamine oxidase (DAO), D-lactate and lipopolysaccharide (LPS) serum concentrations. GOS treatment also altered the short-chain fatty acid (SCFA) concentration in colonic contents and alleviated mucosal damage. Our findings suggested that GOS supplementation can repair gut microbiota dysbiosis, restore normal intestinal permeability and eliminate excess endotoxins from peripheral blood. Additionally, GOS is a potentially useful prebiotic for auxiliary therapy for alcohol addiction.

Founder parents have contributed significantly to the improvement of wheat breeding and production. In order to investigate the genetic characteristics of founder parents and widely planted cultivars, Mazhamai (M), Biyumai (B) and six sibling lines (BM1–6) derived from the cross M×B were phenotyped for eight yield-related traits over multiple years and locations and genotyped using the the wheat 90K single nucleotide polymorphism (SNP) assay. BM4 has been used as a founder parent, and BM1 has been widely planted, whereas BM2, 3, 5, and 6 have not been used extensively for breeding or planting in China. Phenotypic comparisons revealed that BM4 and BM1 displayed a better overall performance than the other sibling lines. BM1 showed higher thousand-grain weight than BM4, whereas BM4 exhibited lower coefficient of variation for most of the yield-related traits across different years and locations, indicating that BM4 was widely adaptable and more stable in different environments. SNP analysis revealed that BM4 and BM1 inherited similar proportions of the M genome but are dissimilar to BM2, 3, 5, and 6. Both BM1 and BM4 have specific alleles that differ from the other BM lines, and most of these alleles are concentrated in specific chromosomal regions that are found to associate with favorable QTLs, these SNPs and their surrounding regions may carry the genetic determinants important for the superior performance of the two lines. But BM4 has more genetic diversity than BM1 with more specific alleles and pleiotropic regions, indicating that the genome of BM4 may be more complex than the other sibling lines and has more favorable gene resources. Our results provide valuable information that can be used to select elite parents for wheat and self-pollinating crop breeding.

Background/Purpose: Fluoride and epigallocatechin gallate (EGCG) have been proven to prevent dental caries. The purpose of this study was to evaluate the effects of fluoride and EGCG on soft-drink-induced dental erosion in vitro. Methods: Forty enamel and dentin specimens were prepared from extracted human teeth. The specimens were divided into 4 groups and treated separately with distilled water (as control), 0.5 M sodium fluoride (NF), 400 μM EGCG (EG), and a solution containing 0.5 M NaF and 400 μM EGCG (FG). Cyclic erosive treatment was performed according to the experimental procedures. The specimens were analyzed using laser scanning confocal microscopy, scanning electron microscopy, and a microhardness tester. The data were analyzed using ANOVA and Bonferroni's post hoc test. The significance level was set at 5%. Results: The amount of substance loss was lower in the NF and EG groups than in the control group (p

Grain number per spike (GNPS) is a major factor in wheat yield breeding. A new wheat germplasm Pubing 3504 shows superior features in spike traits. To elucidate the genetic basis of spike and yield related traits in Pubing 3504, 282 F2:3 families were generated from the cross Pubing 3504×Jing 4839, and seven spike and yield related traits, including GNPS, spike length (SL), kernel number per spikelet (KPS), spikelet number per spike (SNS), thousand-grain weight (TGW), spike number per plant (SNP), and plant height (HT) were investigated. Correlation analysis indicated significant positive correlations between GNPS and spike-related traits, including KPS, SNS, and SL, especially KPS. A genetic map was constructed using 190 polymorphic simple sequence repeat (SSR), expressed sequence tag (EST)-SSR, and sequence-tagged-site (STS) markers. For the seven traits measured, a total of 37 quantitative trait loci (QTLs) in a single-environment analysis and 25 QTLs in a joint-environment analysis were detected. Additive effects of 70.3% (in a single environment) and 57.6% (in a joint environment) of the QTLs were positively contributed by Pubing 3504 alleles. Five important genomic regions on chromosomes 1A, 4A, 4B, 2D, and 4D could be stably detected in different environments. Among these regions, the marker interval Xmag834–Xbarc83 on the short arm of chromosome 1A was a novel important genomic region that included QTLs controlling GNPS, KPS, SNS, TGW, and SNP with stable environmental repeatability. This genomic region can improve the spike trait and may play a key role in improving wheat yield in the future. We deduced that this genomic region was vital to the high GNPS of Pubing 3504.

Background/Objective: To analyze the preoperative factors associated with the need for secondary surgery following primary urethroplasty. Methods: This study utilized a subset of the National Health Insurance Research Database, which includes the data on all paid medical benefit claims from 1997 to 2007, for 1 million beneficiaries in 2005. We analyzed the claims data for all patients with hypospadias who had undergone primary urethroplasty. The characteristics of the patients, surgeons, and hospitals associated with surgical outcomes were analyzed to investigate possible associations with the need for secondary surgery. Results: Among 52,705 live male newborn babies, 218 were diagnosed with hypospadias, of whom 89 received repair surgery. A total of 75 (84.3%) male newborn babies received single hypospadias surgery, and 14 (15.7%) underwent more than two surgical procedures. Univariate analysis demonstrated that the type of hypospadias and the surgeon caseload volume were significantly associated with the need for additional hypospadias surgery (p = 0.02 and p = 0.03, respectively). In multivariate analysis, the type of hypospadias (distal vs. proximal, odds ratio, 0.25; p = 0.03) and the surgeon caseload volume (high vs. low, odds ratio, 0.04; p = 0.05) were significantly correlated with secondary operation. Conclusion: The type of hypospadias and the surgeon caseload volume were significantly associated with the need for secondary hypospadias surgery. The findings of this study provide important information on the outcomes of hypospadias repair for parents and specialists.