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Abnormally high follicle-stimulating hormone (FSH) has been reported to associate with cardiovascular diseases in prostate cancer patients with specific androgen deprivation therapy and in menopausal women. All of the cardiovascular diseases were involved in atherosclerosis. However, the pathogenic mechanism of FSH-associated atherosclerosis remains uncertain. Apolipoprotein E–deficient mice were chosen to develop atherosclerosis, of which the plaques were analyzed with administration of short- and long-term FSH imitating androgen deprivation therapy–induced and menopausal FSH elevation. The study showed that short- and long-term exposure of FSH significantly accelerated atherosclerosis progression in apolipoprotein E–deficient mice, manifested as strikingly increased plaques in the aorta and its roots, increased macrophage content, reduced fibrin, and an enlarged necrotic core, suggesting a decrease in plaque stability. Furthermore, expression profiles from the Gene Expression Omnibus GSE21545 dataset revealed that macrophage inflammation was tightly associated with FSH-induced atherosclerotic progression. The human monocyte cell line THP-1 was induced by PMA and worked as a macrophage model to detect inflammatory factors and cellular functions. FSH remarkably promoted the expression of IL-1β in macrophages and strikingly increased the chemotactic migratory capacity of macrophages toward MCP-1, but the promigratory capacity of FSH was attenuated in foam cells. Overall, we revealed that FSH significantly promoted the inflammatory response and migration of macrophages, thereby provoking atherosclerosis development.

Studying the insertion process of cochlear implant (CI) electrode array (EA) is important to ensure successful, sufficient, and safe implantation. A three-dimensional finite element (FE) model was developed to simulate the insertion process. The cochlear structures were reconstructed from an average statistical shape model (SSM) of human cochlea. The electrode is simplified as a long and tapered beam of homogeneous elastic materials, contacting and interacting with the stiff cochlear structures. A quasi-static insertion simulation was conducted, the insertion force and the contact pressure between the electrode and the cochlear wall, were calculated to evaluate the smoothness of insertion and the risk of potential cochlear trauma. Based on this model, different EA designs were analyzed, including the Young's modulus, the straight or bended shape, the normal or a more tapped section size. The influence of the insertion angle was also discussed. Our simulations indicate that reducing the EA Young's modulus, tapering and pre-bending are effective ways to ensure safe and successful EA implantation. This model is beneficial for optimizing EA designs and is potentially useful for designing patient-specific CI surgery.

BackgroundThe increased risk of cardiovascular events in patients prescribed macrolides has been subject to debate for decades.MethodsMedline, EMBASE databases and ClinicalTrials.gov were searched from inception until August 31, 2022 for studies investigating the link between macrolides and cardiovascular risk. A meta-analysis was performed using a random-effects model.ResultsA total of 80 studies involving 39,374,874 patients were included. No association was found between macrolides and all-cause death. However, compared with the non-macrolide group, macrolides were associated with a significantly increased risk of ventricular arrhythmia or sudden cardiac death (VA or SCD) (azithromycin, relative ratio [RR]: 1.53; 95% confidence interval [CI]: 1.19 to 1.97; clarithromycin, RR: 1.52; 95% CI: 1.07 to 2.16). Besides, administration of macrolides was associated with a higher risk of cardiovascular disease (CVD) death (azithromycin, RR: 1.63; 95% CI: 1.17 to 2.27) and a slightly increased risk of myocardial infarction (MI) (azithromycin, RR: 1.08; 95% CI: 1.02 to 1.15). Interestingly, no association was observed between roxithromycin and adverse cardiac outcomes. Increased risk of VA or SCD was observed for recent or current use of macrolides, MI for former use, and CVD death for current use.ConclusionAdministration of macrolide antibiotics and timing of macrolide use are associated with increased risk for SCD or VTA and cardiovascular death, but not all-cause death.

Objective The purpose of this study was to investigate the value of left atrial (LA) volume and strain by 4D auto left atrial quantification (LAQ) for differentiating pre- and post-capillary pulmonary hypertension (PH), and compare the discriminative ability with echocardiographic pulmonary to left atrial global strain ratio (ePLAGS). Methods A total of ninety-eight subjects screened for intermediate to high probability of PH were prospectively enrolled in this study. Clinical history and laboratory data of all the patients were collected. All the patients underwent comprehensive transthoracic echocardiography and then LA volume and strain were measured by dedicated commercial software specially designed for LA 4D analysis. Results According to pulmonary arterial wedge pressure, the participants were divided into two groups: pre-capillary PH Group (n=39, age 53±24 year) and post-capillary PH Group (n=59, age 57 ± 18 year). LAVImax, LAVImin and LAVIpreA significantly increased, while LASr and LAScd obviously decreased in post-capillary PH group when comparing with pre-capillary PH group. Multivariate logistic regression analysis showed LAVImax (OR: 1.40; 95% CI, 1.05–1.87; P = 0.021) and LAScd (OR: 1.76; 95% CI, 1.18–2.49; P = 0.004) were powerful independent predictors for detecting post-capillary PH. The ROC analysis indicated that LAVImax (AUC=0.82, p < 0.001) and LAScd (AUC=0.78, p Conclusions LAVImax and LAScd measured by 4D auto LAQ were powerful parameters for distinguishing pre-capillary PH from post-capillary PH.

Background The underlying mechanism of neurosyphilis was not fully understood. Purpose To assess gray matter (GM) microstructure in patients with early-stage neurosyphilis without overt conventional magnetic resonance imaging (MRI) abnormality using voxel-based morphometry (VBM) and surface-based morphometry (SBM) analyses. Material and Methods Three-dimensional high-resolution T1-weighted imaging data from 19 individuals with neurosyphilis and 19 healthy controls were analyzed. A battery of neuropsychological tests was performed before each MRI examination. The differences of GM volume and cerebral cortical morphological data between the two groups were compared. The correlations between MRI metrics and neuropsychology/laboratory tests in the patient group were investigated. Results Regional decreased GM volumes in patients with neurosyphilis were found in the left frontal cortices (Rolandic operculum, middle frontal, and precentral) and bilateral temporal/occipital cortices (bilateral middle temporal, left lingual, and right middle occipital) ( P Conclusion Early-stage neurosyphilis without conventional MRI abnormality presented regional GM volume reduction and cortical morphological changes, which might be related to cognitive impairment and intra-cranial infection. VBM and SBM analyses might be useful for understanding the underlying neural trait of neurosyphilis.

Amorphous InGaN films were deposited on p-Si(100) substrates using a self-refited pulsed laser deposition system with double laser light paths and two-component target. The effects of laser energy on the microstructure, electrical and photovoltaic performances of InGaN films as well as n-InGaN/p-Si heterojunction solar cells were investigated. The results show that all the films are rich in Ga and poor in In, and the (In + Ga)/N atomic ratios are greater than 1. As the laser energy increases, In composition increases gradually and reaches to a maximum of 4.6 at.%. The PL spectra indicates that the band gap of the films decrease with the increase of laser energy. Meanwhile, the resistivity of InGaN film is decreased in two orders of magnitude due to the increasing of carrier concentration. Under the illumination of AM 1.5G solar simulator, the maximum power conversion efficiency of amorphous n-InGaN/p-Si heterojunction solar cells is 0.73% with an open circuit voltage of 2.41 V and short current density of 0.69 mA/cm2 at the laser energy of 175 mJ/pulse.

Object detection is one of the main tasks in computer vision and has made great progress in recent years. However, the performance of target detectors is significantly dropped by the differences between existing datasets and application scenarios, leading to the so‐called domain shift problem. To address such an issue, a novel co‐teaching based pseudo label refinery framework for cross‐domain object detection is developed, which cooperates with two models to select data from target domain for each other. This strategy can effectively purify the predicted pseudo labels and resist noisy labels. Specifically, the framework consists of two encoders (i.e. structure encoder and global encoder), two classifiers and one discriminator, in which structure encoder is used to extract structural features that are not disturbed by colour, and the global encoder is used to extract the complete discriminant features. The two encoders are each followed by a classifier. In training, the structure and global encoder with labelled source samples are first trained, so that it has the initial recognition ability. Then the samples assigned are used with pseudo labels by the classifier following the structure encoder to fine‐tune the global encoder which pre‐trained on the labelled source domain and obtain the refined labels for the target data. With the refined labels, the structure encoder is further optimised on the target domain. During this process, the proposal is to cross use the two classifiers to promote the mutual transfer of complementary capabilities of the two encoders. Moreover, a novel residual channel attention block (RCA) embedded with salient features is designed to pay more attention to the target regions. Extensive experiments demonstrate that the developed framework can generate clean labels for unlabelled target data and boost the performance of cross domain object detection. The code is available at http://www.msp‐lab.cn:1436/msp/cbplr‐master.

The discovery and in-depth study of non-biocatalytic applications of active biomolecules are essential for the development of biomimicry. Here, the effect of intermolecular hydrogen-bonding traction on the CO

To establish an optimized model of bone marrow suppression induced by cytarabine (Ara-C) in C57BL/6 mice and preliminarily explore the mechanism of myelosuppression based on the cycle and apoptosis of BMNC.C57BL/6 mice were intraperitoneally injected with Ara-C 50, 100 and 200 mg/kg for 7 days, respectively. The survival rate and body weight of C57BL/6 mice were monitored. The number of peripheral blood cells and bone marrow nucleated cells (BMNC) was detected, and the morphology of bone marrow, thymus and spleen were measured on the 7th, 14th and 21st day of the experiment. The cycle and apoptosis of BMNC were also detected by flow cytometry.Ara-C 200 mg/kg caused 46.7% mortality in mice, and other doses had no significant effect on mortality. All doses of Ara-C induced bone marrow suppression in mice, as shown by a decrease in the number of peripheral blood cells (WBC, Neu, RBC, PLT) and BMNC (P0.05), decrease in bone marrow hyperplasia, accompanied by immunosuppression and compensatory hematopoiesis of the spleen, and the above manifestations and duration were dose-dependent. Among them, the myelosuppression caused by Ara-C 50 mg/kg recovered quickly, and caused by Ara-C 200 mg/kg was too severe. The result of flow cytometry showed that Ara-C could cause S and GAra-C can induce myelosuppression in mice with a dose-dependent severity and duration, and the model of myelosuppression with Ara-C 100 mg/kg is more optimized. The mechanism is related to the inhibition of BMNC proliferation and the promotion of apoptosis.阿糖胞苷诱发C57BL/6小鼠骨髓抑制的模型建立及其机制研究.建立阿糖胞苷（Ara-C）诱发C57BL/6小鼠骨髓抑制的优化模型，并从细胞周期和凋亡角度初步探讨Ara-C诱发骨髓抑制的机制.C57BL/6小鼠分别用Ara-C 50、100和200 mg/kg连续腹腔注射7 d后，监测小鼠生存率和体重变化，于实验7、14和21 d分别检测外周血象、骨髓有核细胞（BMNC）数量，HE染色观察骨髓、胸腺和脾形态，同时采用流式细胞术检测BMNC周期和凋亡.Ara-C 200 mg/kg造成小鼠的死亡率为46.7%，其他剂量对小鼠死亡率无明显影响。3个不同剂量的Ara-C均可诱发小鼠出现骨髓抑制，表现为外周血细胞（WBC、Neu、RBC、PLT）数下降和BMNC数量减少（P＜0.05），骨髓增生下降，伴随脾脏代偿造血和免疫抑制，以上表现与持续时间呈剂量依赖性，其中Ara-C 50 mg/kg组骨髓抑制恢复较快，200 mg/kg组骨髓抑制严重且恢复慢。流式细胞术检测结果显示，Ara-C可造成BMNC的S期和GAra-C可诱发小鼠出现骨髓抑制，严重程度与持续时间呈剂量依赖性，以Ara-C 100 mg/kg造成骨髓抑制的模型更为优化，其机制与Ara-C抑制BMNC增殖和促进凋亡相关.

PurposeTo assess the association between sarcopenia and the risk of early biliary infection (EBI) after percutaneous transhepatic biliary stent (PTBS) placement in patients with inoperable biliary tract cancer (BTC).Patients and methodsIn this single center, retrospective observational study, patients diagnosed with inoperable BTC undergoing PTBS placement between January 2013 and July 2021 were enrolled. Preoperative sarcopenia was defined based on skeletal muscle mass measured by computed tomography images on the level of third lumbar vertebra within one month before PTBS placement. Patients were divided into two groups in accordance with the status of sarcopenia. Univariate and further multivariate logistic analyses were performed to determine predictors for EBI. Stratified and interactive analyses were conducted to investigate the stability of results. Further receiver operating characteristic curve was performed to determine the predictive value of sarcopenia on EBI after PTBS placement.ResultsTotally, 134 patients were included in this retrospective study, with 45 (33.6%) patients characterized as sarcopenia. The incidence rate of EBI was 26.9% (36/134). Multivariate analyses demonstrated that sarcopenia [Odds ratio (OR), 2.75; 95%CI: 1.11–6.77; P=0.028], obstruction length (OR, 1.04; 95%CI: 1.00–1.08; P=0.030) and diabetes (OR, 2.46; 95%CI: 1.01–5.96; P=0.047) were significant predictors of EBI. There were no significant interactions in different subgroups (P for interaction > 0.05). Moreover, the areas under the curves (AUC) revealed that the combined index containing sarcopenia, obstruction length, and diabetes showed the better predictive value (AUC= 0.723) than either one alone.ConclusionSarcopenia increased the risk of EBI in patients with inoperable BTC after PTBS placement. Preoperative assessment of sarcopenia may aid in risk stratification. Patients with sarcopenia should be given intensive monitoring.

Genotyping of folate metabolism genes is of great importance in disease diagnosis and prevention. However, most current detection methods used for folate metabolism gene genotyping are based on sequencing and chips, which suffer from a high cost and laborious and time-consuming procedures. Herein, we reported a multiplex asymmetric PCR-HRM strategy for identifying genotypes of folate metabolism genes in a single tube. The proposed multiplex PCR-HRM assay has been successfully applied to identify the genotypes of folate metabolism genes, methylene tetrahydrofolate reductase (C677T, A1298C) and methionine synthase reductase A66G, on 1 μL of genomic DNA (gDNA) samples directly released from blood specimens, and the genotyping results were 100% consistent with the results of sequencing. The assay allows us to accurately detect the genotypes of gDNA with the detection limit down to 1 ng, which meets the clinical requirement. What is more, the capacity of resistance to aerosol pollution of the multiplex asymmetric PCR-HRM biosensing was first addressed and has been evaluated as it can withstand contamination of roughly 12.5-25% interfering nucleic acids. Because of the advantages of multiplex detection, high accuracy, and resistance to aerosol pollution and having no open tube procedure, this approach would pave the way for establishing a fast and cost-effective platform for folate metabolism gene genotyping and other SNP genotyping in clinical diagnostics.

Background and objectiveCoronary artery bypass grafting (CABG) is the reference standard intervention in coronary artery disease (CAD) patients with three-vessel disease (3VD). We aimed to evaluate the predictive value of left ventricular (LV) dyssynchrony for short-term adverse outcomes in patients with 3VD undergoing CABG with preserved or mildly reduced LV ejection fraction (LVEF).Materials and methodsThis study involved ninety-five 3VD patients with preserved or mildly reduced LVEF undergoing scheduled on-pump CABG. The pre-operative diameters and volumes of LV and LVEF were obtained by two-dimensional echocardiography. LV dyssynchrony parameters were acquired by real-time three-dimensional echocardiography (RT-3DE) and analyzed by HeartModel quantification software. And the perfusion index of LV was obtained by contrast echocardiography. The clinical endpoints of short-term adverse outcomes comprised 30-day mortality and/or composite outcomes of postoperative complications. Univariate and multivariate logistic regression analyses were used to identify risk factors for the occurrence of post-CABG short-term adverse outcomes.ResultsShort-term adverse outcomes occurred in 12 (12.6%) patients. These patients had higher LV dyssynchrony parameters obtained through RT-3DE. The standard deviation (SD) of the time to minimum systolic volume (Tmsv) corrected by heart rate over 16 segments (Tmsv16-SD%) [odds ratio (OR), 1.362; 95% confidence interval (CI) (1.090–1.702); P = 0.006], one of the LV dyssynchrony parameters, was independently associated with short-term adverse outcomes. Patients with poor synchronization tended to spend more time in the intensive care unit (ICU) and hospital after surgery.ConclusionPre-operative LV dyssynchrony parameter Tmsv16-SD% obtained through RT-3DE could be a useful additional predictor of postoperative short-term adverse outcomes in 3VD patients with preserved or mildly reduced LVEF undergoing CABG.

This study aims to investigate the effect of atractylenolide Ⅲ(ATL-Ⅲ) on hydrogen peroxide(H_2O_2)-induced endoplasmic reticulum stress and apoptosis of H9 c2 cells via the ROS/GRP78/caspase-12 signaling pathway.The binding activity of ATL-Ⅲ to GRP78 was determined by molecular docking.The result showed that ATL-Ⅲ had a good binding activity to GRP78, and the binding activity of ATL-Ⅲ was stronger than that of its specific inhibitor.The endoplasmic reticulum stress model of H9 c2 was established by H_2O_2(100 μmol·L~(-1)) treatment.Five groups were designed: blank control group, model group, and ATL-Ⅲ(15, 30, and 60 μmol·L~(-1)) groups.Apoptosis was detected by Hoechst/PI double staining and flow cytometry.The levels of superoxide dismutase(SOD), malondialdehyde(MDA), and lactate dehydrogenase(LDH) were measured by colorimetry.The levels of reactive oxygen species(ROS) and calcium(Ca~(2+)) in cytoplasm were determined by the fluorescence probe DCFH-DA and the calcium fluorescence probe Flou-4, respectively.The protein levels of GRP78, caspase-12, and caspase-3 were determined by Western blot, and the mRNA levels of GRP78 and caspase-12 by RT-qPCR.N-acetyl-L-cysteine(NAC) and 4-phenylbutyric acid(4-PBA) were respectively used to inhibit ROS and GRP78, and then the mechanism of ATL-Ⅲ in protecting the cells from endoplasmic reticulum stress induced by H_2O_2 were deduced.ATL-Ⅲ(15, 30, and 60 μmol·L~(-1)) decreased the apoptosis rate and ROS, MDA, and LDH levels(Plt;0.01), increased the SOD activity(Plt;0.01), and down-regulated the protein levels of GRP78, caspase-12, and caspase-3 and the mRNA levels of GRP78 and caspase-12(Plt;0.05).The addition of NAC decreased the apoptosis rate and ROS, MDA, GRP78, caspase-12, and caspase-3 levels(Plt;0.01), while it elevated the SOD level(Plt;0.01).The addition of 4-PBA also decreased the apoptosis rate and the levels of GRP78, caspase-12, caspase-3, and Ca~(2+)(Plt;0.01).The effect of inhibitors were consistent with that of ATL-Ⅲ.In conclusion, ATL-Ⅲ can protect H9 c2 cardiomyocytes by regulating ROS/GRP78/caspase-12 signaling pathway to inhibit H_2O_2-induced endoplasmic reticulum stress and apoptosis.

LATERAL ORGAN BOUNDARIES DOMAIN (LBD) genes encode plant-specific transcription factors that participate in regulating various developmental processes. In this study, we genetically characterized PagLBD3 encoding an important regulator of secondary growth in poplar (Populus alba × Populus glandulosa). Overexpression of PagLBD3 increased stem secondary growth in Populus with a significantly higher rate of cambial cell differentiation into phloem, while dominant repression of PagLBD3 significantly decreased the rate of cambial cell differentiation into phloem. Furthermore, we identified 1756 PagLBD3 genome-wide putative direct target genes (DTGs) through RNA sequencing (RNA-seq)-coupled DNA affinity purification followed by sequencing (DAP-seq) assays. Gene Ontology analysis revealed that genes regulated by PagLBD3 were enriched in biological pathways regulating meristem development, xylem development, and auxin transport. Several central regulator genes for vascular development, including PHLOEM INTERCALATED WITH XYLEM (PXY), WUSCHEL RELATED HOMEOBOX4 (WOX4), Secondary Wall-Associated NAC Domain 1s (SND1-B2), and Vascular-Related NAC-Domain 6s (VND6-B1), were identified as PagLBD3 DTGs. Together, our results indicate that PagLBD3 and its DTGs form a complex transcriptional network to modulate cambium activity and phloem/xylem differentiation.

Aberrant expression of microRNA-497 (miR-497) is associated with tumor progression, but the molecular mechanisms in tumorigenesis remain largely unknown. Here, we report that miR-497 expression is downregulated in esophageal squamous cell carcinoma (ESCC) clinical samples. Consistently, upregulation of miR-497 inhibits ESCC cell malignant properties and tumor growth in vivo. Importantly, we uncovered that miR-497 upregulation suppressed ESCC cell growth and tumor growth by inhibiting Smurf2. Mechanistically, we showed that Smurf2 was a target of miR-497, and mediated YY1 expression to elevate HIF2α expression, thereby enhancing the malignancy of ESCC cells. Together, our study uncovered the role of the miR-497-mediated Smurf2/YY1/HIF2α axis in tumor growth and metastasis, which might provide potential therapeutic targets for human ESCC.

ZnO nanowires (ZnO NWs) were synthesized by hydrothermal method on Si (100) substrates, in which an insulating MgO layer deposited using sol–gel method was inserted between the seed layer and Si substrate. The effects of MgO layer on the microstructure, luminescence and electrical properties of ZnO NWs as well as n-ZnO NWs/p-Si heterojunction LEDs were investigated. With the insertion of MgO layer, well-aligned ZnO NWs with good crystalline quality are obtained, which can be attributed to the smooth seed layer with homogeneous globular particles. The electroluminescence spectra of n-ZnO NWs/MgO/p-Si heterojunction LEDs exhibit a broad emission band from near ultraviolet to yellow-green region. n-ZnO NWs/MgO/p-Si heterojunction also shows an enhanced ultraviolet photoluminescence efficiency, and its defect-related visible emission is greatly suppressed compared with that of n-ZnO NWs/p-Si heterojunction. The current–voltage curves of both heterojunction LEDs present a typical rectifying behavior, but the rectification ratio increases almost 5 times by inserting MgO layer, which is ascribed to a reduction in the leakage current under reverse bias voltage.

It is well-known that effective charge transfer within the catalyst structure is critical to the improvement of the performance of catalytic reaction. Herein, we reported three functionalized polyo...

Fear of progression (FoP) is a prevalent psychological strain for cancer patients associated with poor quality of life and psychological morbidity. However, little evidence exists on FoP in children with cancer. Our study aimed to determine prevalence and correlates of FoP of cancer in children. From December 2018 to March 2019, cancer patients from Children’s Hospital in Chongqing, Southwest China, were recruited. A Chinese version of Fear of Progression Questionnaire-Short Form (FoP-Q-SF) was adopted to assess children’ FoP. Descriptive statistics (percentages, median, and interquartile range), non-parametric tests, and multiple regression analyses were performed on these data. Prevalence of high-level FoP was 43.75% among these 102 children. Multiple regression analysis showed that reproductive system tumors (beta = 0.315, t = 3.235 95% CI [3.171, 13.334]), and level of psychological care needs (beta = −0.370, t = −3.793 95% CI [−5.396, −1.680]) were independent predictors of FoP. Regression model explained 27.10% of all included variables (adjusted R square = 27.10%). As with adults with cancer, children with cancer also have FoP. More attention should be paid to FoP in children with reproductive tumors and in children who need psychological support. More access to psychological support should be offered to reduce FoP and to improve their quality of life.