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Abstract The central nervous system has been implicated in the age-induced reduction in adipose tissue lipolysis. However, the underlying mechanisms remain unclear. Here, we show the expression of SLC7A14 is reduced in proopiomelanocortin (POMC) neurons of aged mice. Overexpression of SLC7A14 in POMC neurons alleviates the aging-reduced lipolysis, whereas SLC7A14 deletion mimics the age-induced lipolysis impairment. Metabolomics analysis reveals that POMC SLC7A14 increased taurochenodeoxycholic acid (TCDCA) content, which mediates the SLC7A14 knockout- or age-induced WAT lipolysis impairment. Furthermore, SLC7A14-increased TCDCA content is dependent on intestinal apical sodium-dependent bile acid transporter (ASBT), which is regulated by intestinal sympathetic afferent nerves. Finally, SLC7A14 regulates the intestinal sympathetic afferent nerves by inhibiting mTORC1 signaling through inhibiting TSC1 phosphorylation. Collectively, our study suggests the function for central SLC7A14 and an upstream mechanism for the mTORC1 signaling pathway. Moreover, our data provides insights into the brain–gut–adipose tissue crosstalk in age-induced lipolysis impairment.

Objective: To develop an artificial intelligence deep neural network (AI-DNN) algorithm to analyze 12-lead electrocardiogram (ECG) for detection of acute pulmonary embolism (PE) and PE categories. Patients and Methods: A cohort of patients seen between January 1, 1999, and December 31, 2020, from across the Mayo Clinic Enterprise with computed tomography pulmonary angiogram (CTPA) and ECG performed ±6 hours was identified. Natural language processing algorithms were applied to radiology reports to determine the diagnosis of acute PE, acute right ventricular strain pulmonary embolism (RVSPE), saddle pulmonary embolism (SADPE), or no PE. Diagnostic performance parameters of the AI-DNN reported were area under the receiver operating characteristics curve (AUROC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: A cohort of patients with CTPA report and ECG consisted of 79,894 patients including 7423 (9.3%) with acute PE, among whom 1138 patients had RVSPE or SADPE. Artificial intelligence deep neural network predicted acute PE with a modest accuracy of AUROC of 0.69 (95% CI, 0.68-0.71), sensitivity of 63.5%, specificity of 64.7%, PPV of 15.6%, and NPV of 94.5%. The AI-DNN prediction using the same algorithm for RVSPE or SADPE was higher (AUROC, 0.84; 95% CI, 0.81-0.86) with a sensitivity of 80.8%, specificity of 64.7.8%, PPV of 3.5%, and NPV of 99.5%. Conclusion: An AI-based analysis of 12-lead ECG shows modest detection power for acute PE in patients who underwent CTPA, with higher accuracy for high-risk PE. Moreover, with the high NPV, it has the clinical potential to exclude high-risk PE quickly and correctly.

Abstract Radiation‐induced heart disease (RIHD) is a heterogeneous, delayed, and potentially fatal adverse reaction to radiation that can damage all structures of the heart, including the pericardium, myocardium, coronary arteries, valves, and conduction system, leading to a series of diseases. Acute and chronic disease processes play a role in the development of RIHD, the onset times of which range from months to decades. However, the clinical manifestations of RIHD are usually insidious, overlap with several other diseases, and lack specificity. Cardiovascular imaging is essential for early diagnosis, follow‐up, and outcome assessment in patients with RIHD. This review first describes the pathogenesis and clinical manifestations of RIHD before providing an overview of the practical approaches and research advances in multimodal cardiovascular imaging in patients with RIHD, including echocardiography, cardiac magnetic resonance (CMR) and nuclear medicine, and cardiac computed tomography (CT). Then, the value of new cardiac imaging assessments for the early diagnosis of RIHD is described, particularly with relation to speckle‐tracking echocardiography, extracellular volume fraction assessment as a quantitative CMR technique, CMR myocardial strain assessment, positron emission tomography‐CT myocardial perfusion imaging, CT‐ECV, and CT strain assessment, amongst others. In addition, the advantages and disadvantages of each screening technique are compared with the aim of better guiding the follow‐up and diagnosis of subclinical RIHD and preventing cardiovascular events.

Abstract Objective Catalpol (CAT) has various pharmacological activities and plays a protective role in cerebral ischemia. It has been reported that CAT played a protective role in cerebral ischemia by upregulaing NRF1 expression. Bioinformatics analysis reveals that NRF1 can be used as a transcription factor to bind to the histone acetyltransferase KAT2A. However, the role of KAT2A in cerebral ischemia remains to be studied. Therefore, we aimed to investigate the role of CAT in cerebral ischemia and its related mechanism. Methods In vitro, a cell model of oxygen and glucose deprivation/reperfusion (OGD/R) was constructed, followed by evaluation of neuronal injury and the expression of METTL3, Beclin-1, NRF1, and KAT2A. In vivo, a MCAO rat model was prepared by means of focal cerebral ischemia, followed by assessment of neurological deficit and brain injury in MCAO rats. Neuronal autophagy was evaluated by observation of autophagosomes in neurons or brain tissues by TEM and detection of the expression of LC3 and p62. Results In vivo, CAT reduced the neurological function deficit and infarct volume, inhibited neuronal apoptosis in the cerebral cortex, and significantly improved neuronal injury and excessive autophagy in MCAO rats. In vitro, CAT restored OGD/R-inhibited cell viability, inhibited cell apoptosis, LDH release, and neuronal autophagy. Mechanistically, CAT upregulated NRF1, NRF1 activated METTL3 via KAT2A transcription, and METTL3 inhibited Beclin-1 via m6A modification. Conclusion CAT activated the NRF1/KAT2A/METTL3 axis and downregulated Beclin-1 expression, thus relieving neuronal injury and excessive autophagy after cerebral ischemia.

To overcome the strength-ductility conflict in particle reinforced aluminum matrix composites (PRAMCs), a novel dual configuration strategy of microstructure was proposed in this work. The dual configuration including both heterogeneous grain structure and hybrid reinforcements was obtained by powder metallurgy, which was designed as submicron-sized SiC particles (SiCsm)/Al and micron-sized SiC particles (SiCm)/2024Al components. Representative alternating coarse grain (CG) bands containing SiCm and ultra fine grain (UFG) bands with dispersed SiCsm were revealed in microstructural characterizations. Compared to corresponding homogeneous composites with the same fraction particles, the dual configuration composite achieved simultaneous enhancement in strength and ductility and remained a comparable Young’s modulus of 98GPa, which represented 442 MPa in yield strength, 590 MPa in ultimate strength and 8.7 % in fracture elongation. The extra strength provided by hetero-deformation induced (HDI) strengthening is a potential dominant strengthening mechanism. The intrinsic toughening mechanisms primarily contribute to HDI strain hardening and enhanced dislocation accumulation capacity, while the extrinsic toughening mechanisms presumably attribute to more uniform microcrack distribution and blunting effect of CG zones on cracks. Our work provides a feasible route including ball milling and powder assembly to preparate high-modulus aluminum matrix composites for strength-ductility balance design.

Many microbes accumulate energy storage molecules such as triglycerides (TAG) and starch during nutrient limitation. In eukaryotic green algae grown under nitrogen-limiting conditions, triglyceride accumulation is coupled with chlorosis and growth arrest. In this study, we show that reactive oxygen species (ROS) actively accumulate during nitrogen limitation in the microalga Chlorella sorokiniana. Accumulation of ROS is mediated by the downregulation of genes encoding ROS-quenching enzymes, such as superoxide dismutases, catalase, peroxiredoxin, and glutathione peroxidase-like, and by the upregulation of enzymes involved in generating ROS, such as NADPH oxidase, xanthine oxidase, and amine oxidases. The expression of genes involved in ascorbate and glutathione metabolism is also affected under this condition. ROS accumulation contributes to the degradation of monogalactosyl diacylglycerol (MGDG) and thylakoid membrane remodeling, leading to chlorosis. Quenching ROS under nitrogen limitation reduces the degradation of MGDG and the accumulation of TAG. This work shows that ROS accumulation, membrane remodeling, and TAG accumulation under nitrogen limitation are intricately linked in the microalga C. sorokiniana.

IntroductionNutritional deficiency occurs frequently during pregnancy and breastfeeding. Tryptophan (Trp), an essential amino acid which is critical for protein synthesis, serves as the precursor for serotonin, melatonin, and kynurenine (Kyn). The imbalance between serotonin and kynurenine pathways in Trp metabolism is closely related to inflammation and depression. This study assessed the effects of Trp deficiency on mouse early pregnancy.MethodsEmbryo implantation and decidualization were analyzed after female mice had been fed diets containing 0.2% Trp (for the control group), 0.062% Trp (for the low Trp group) and 0% Trp (for the Trp-free group) for two months. The uteri of the mice were collected on days 4, 5, and 8 of pregnancy for further analysis.ResultsOn day 8 of pregnancy, the number of implantation sites were found to be similar between the control and the low Trp groups. However, no implantation sites were detected in the Trp-free group. On day 5 of pregnancy, plane polarity- and decidualization-related molecules showed abnormal expression pattern in the Trp-free group. On day 4 of pregnancy, there was no significant difference in uterine receptivity molecules between the low-Trp group and the control group, but uterine receptivity was abnormal in the Trp-free group. At implantation sites of the Trp-free group, IDO and AHR levels were markedly elevated. This potentially increased levels of Kyn, 2-hydroxy estradiol, and 4-hydroxy estradiol to affect decidualization.ConclusionsTrp-free diet may impair decidualization via the IDO-KYN-AHR pathway.

Wheel polygons can significantly impair the operational quality, service life and ride comfort of railway systems and even threaten the safety of train operations. Timely detection of wheel polygons is of great benefit in formulating a reasonable wheel maintenance strategy. First, to investigate the vibration response of the locomotive under wheel polygon excitation, a locomotive–tack coupled dynamic model is established, taking into account the flexibility of the bogie frame, wheelset, sleeper and track structure. The effects of typical wheel polygons on the vibration behavior of the locomotive under different conditions were studied. Then, the simulation results were used to quantitatively analyze the correlation between the axle box acceleration (ABA) of the locomotive and the wheel-rail system P2 mode, the inherent modal of the wheelset, the vehicle speed, the order and the amplitude of the wheel polygons. Besides, a dataset with multiple working conditions was created from the simulation data and a quantitative wheel polygon detection model was constructed based on the deep learning algorithm. Finally, the effectiveness of the proposed detection method was verified using the real-world data of ABA and wheel polygons. The results show that the proposed method can quickly and accurately detect the dominant features of the wheel polygon, i.e. the wavelength and the corresponding roughness information.

Abstract Background Cisplatin (CDDP)-based chemotherapy is a standard first-line treatment for metastatic bladder cancer (BCa) patients, and chemoresistance remains a major challenge in clinical practice. Circular RNAs (circRNAs) have emerged as essential regulators in carcinogenesis and cancer progression. However, the role of circRNAs in mediating CDDP chemosensitivity has yet to be well elucidated in BCa. Methods CircSTX6 (hsa_circ_0007905) was identified by mining the public circRNA datasets and verified by Sanger sequencing, agarose gel electrophoresis, RNase R treatment and qRT-PCR assays. Then, function experiments were performed to evaluate the effects of circSTX6 on BCa metastasis. Luciferase reporter assay, RNA pull-down, RNA immunoprecipitation (RIP), RNA stability assay, Fluorescence in situ hybridization (FISH) and Immunofluorescence (IF) were conducted to evaluate the interaction among circSTX6, miR-515-3p, PABPC1 and SUZ12. Animal experiments were performed to explore the function of circSTX6 in tumor metastasis and CDDP sensitivity. Results We identified that circSTX6 was significantly upregulated in clinical samples and cells of BCa. Functionally, circSTX6 promoted cell migration and invasion both in vitro and in vivo. Mechanistically, circSTX6 could act as a miR-515-3p sponge and abolish its effect on SUZ12. Moreover, circSTX6 was confirmed to increase the stability of SUZ12 mRNA by interacting with a mRNA stabilizer PABPC1 and subsequently promote the expression of SUZ12. Importantly, silencing of circSTX6 improved the chemosensitivity of CDDP-resistant bladder cancer cells to CDDP. Furthermore, in vivo analysis supported that knockdown of circSTX6 attenuated CDDP resistance in BCa tumors. Conclusion These studies demonstrate that circSTX6 plays a pivotal role in BCa metastasis and chemoresistance, and has potential to serve as a therapeutic target for treatment of BCa.

Abstract Objective To explore the potential mechanism of Yougui Wan on deformed lumbar intervertebral disk structure in rats. Methods Thirty male Sprague–Dawley rats were randomly divided into 3 groups, with 10 rats in each group. The animals in the blank control group were healthy rats without specific treatment, and those in the model group and traditional Chinese medicine (TCM) group were used to establish the intervertebral disk degeneration (IDD) model by puncturing the annulus. Four weeks after modeling, rats in the TCM group were administered Yougui Wan by gavage for 2 consecutive weeks. Serum interleukin-6 (IL-10), macrophage migration inhibitory factor (MIF) and tumor necrosis factor alpha (TNF-α) levels were measured by ELISA, and the protein expression levels of collagen II and Notch1 in intervertebral disk tissues were examined by Western blotting. Apoptosis was detected by the TUNEL method. Results Compared with those in the blank group, IL-10, MIF and TNF-α levels in the model group and TCM group were increased (P

Full-length grouted bolts play a crucial role in geotechnical engineering thanks to their excellent stability. However, few studies have been concerned with the degrading performance of grouted rock bolts caused by extensive and continuous heat conduction from surrounding rocks in high-geothermal tunnels buried more than 100 m (temperature from 28 °C to 100 °C). To investigate the damage mechanism, we examined the time-varying behaviors of grouted rock bolts in both constant and variable temperature curing environments and their damage due to the coupling effects of high temperature and humidity through mechanical and micro-feature tests, including uniaxial compression test, pull-out test, computed tomography (CT) scans, X-ray diffraction (XRD) test, thermogravimetric analysis (TGA), etc., and further analyzed the relationship between grout properties and anchorage capability. In order to facilitate a rapid assessment and control of the anchorage performance of anchors in different conditions, results of the interface bond degradation tests were correlated to environment parameters based on the damage model of interfacial bond stress proposed. Accordingly, a thermal hazard classification criterion for anchorage design in high-geothermal tunnels was suggested. Based on the reported results, although high temperature accelerated the early-stage hydration reaction of grouting materials, it affected the distribution and quantity of hydration products by inhibiting hydration degree, thus causing mechanical damage to the anchorage system. There was a significant positive correlation between the strength of the grouting material and the anchoring force. Influenced by the changes in grout properties, three failure patterns of rock bolts typically existed. Applying a hot-wet curing regime results in less reduction in anchorage force compared to the hot-dry curing conditions. The findings of this study would contribute to the design and investigations of grouted rock bolts in high-geothermal tunnels.

Background: Pheochromocytoma-induced takotsubo syndrome (Pheo-TTS) significantly increases the risk of adverse events for inpatient. The early identification of risk factors at admission is crucial for effective risk stratification and minimizing complications in Pheo-TTS patients. Methods: We conducted a systematic review combined with hierarchical cluster and feature importance analysis of demographic, clinical and laboratory data upon admission, alongside in-hospital complication data for Pheo-TTS patients. We analyzed cases published in PubMed and Embase from 2 May 2006 to 27 April 2023. Results: Among 172 Pheo-TTS patients, cluster analysis identified two distinct groups: a chest pain dominant (CPD) group (n = 86) and a non-chest pain dominant (non-CPD) group (n = 86). The non-CPD group was characterized by a younger age (44.0 ± 15.2 vs. 52.4 ± 14.4, p < 0.001), a higher prevalence of neurological/psychiatric disorders (53.5% vs. 32.6%), and increased presentation of dyspnea (87.2% vs. 17.4%), pulmonary rales (59.3% vs. 8.1%), and tachycardia (77.9% vs. 30.2%). Additionally, they exhibited more atypical takotsubo syndrome (TTS) imaging phenotypes (55.8% vs. 36.5%, all p < 0.05). The non-CPD group experienced more than a 2-fold increase for in-hospital adverse events compared to the CPD group (70.9% vs. 30.2%, p < 0.001). After adjusting for confounding factors, the absence of chest pain (odds ratio [OR] = 0.407, 95% confidence interval [CI] 0.169–0.979, p = 0.045), the presence of abdominal symptoms (OR = 3.939, 95% CI 1.770–8.766, p = 0.001), pulmonary rales (OR = 4.348, 95% CI 1.857–10.179, p = 0.001), and atypical TTS imaging phenotype (OR = 3.397, 95% CI 1.534–7.525, p = 0.003) remained as independent predictors of in-hospital complications. Conclusions: Clinical manifestations and imaging features at admission help to predict in-hospital complications for Pheo-TTS patients.

The Chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing (CMTM) family, comprising nine members, is involved in the tumorigenesis and progression of various cancers. However, the expression profiles and clinical significance of CMTM family members in hepatocellular carcinoma (HCC) are not fully clarified. In this study, the RNA-sequencing and clinical data were downloaded from The Cancer Genome Atlas (TCGA) databases. The Kaplan–Meier method and the Cox proportional hazards regression analysis were used to evaluate the prognostic significance of CMTM family members. Single-sample gene set enrichment analysis (ssGSEA) and ESTIMATE algorithms were employed to explore the relationship between CMTM family genes and the tumor microenvironment in HCC. Finally, the prognostic CMTM family gene expression was further validated by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical (IHC) staining in clinical HCC tissue specimens. The results indicated that, compared with normal tissues, the expression of CKLF, CMTM1, CMTM3, CMTM4, CMTM7, and CMTM8 were significantly upregulated in HCC, while the expression of CMTM2, CMTM5, and CMTM6 were significantly downregulated in HCC. Univariate and multivariate Cox regression analysis demonstrated that CKLF was an independent prognostic biomarker for the overall survival (OS) of HCC patients. In HCC, the expression of CKLF was found to be correlated with immune cell infiltration, immune-related functions, and immune checkpoint genes. The qRT-PCR and IHC confirmed that CKLF was highly expressed in HCC. Overall, this research suggested that CKLF is involved in immune cell infiltration and may serve as a critical prognostic biomarker, which provides new light on the therapeutics for HCC.

Sensor faults are one of the most common faults that cause performance degradation or functional loss in permanent magnet traction drive systems (PMTDSs). To quickly diagnose faulty sensors, this paper proposes a real-time joint diagnosis method for multi-sensor faults based on structural analysis. Firstly, based on limited monitoring signals on board, a structured model of the system was established using the structural analysis method. The isolation and detectability of faulty sensors were analyzed using the Dulmage–Mendelsohn decomposition method. Secondly, the minimum collision set method was used to calculate the minimum overdetermined equation set, transforming the higher-order system model into multiple related subsystem models, thereby reducing modeling complexity and facilitating system implementation. Next, residual vectors were constructed based on multiple subsystem models, and fault detection and isolation strategies were designed using the correlation between each subsystem model and the relevant sensors. The validation results of the physical testing platform based on online fault data recordings showed that the proposed method could achieve rapid fault detection and the localization of multi-sensor faults in PMTDS and had a good application value.

At present, the research of business environment is limited to conducting surveys on specific groups or measuring data from official databases. The assessment of the business environment largely depends on public perception. Aiming to explore the public perception of business environment, this paper organically combines the big data text mining and sentiment analysis (SA). The results show that the combination of big data text mining and SA can reflect the theme characteristics, reduce the bias of sentiment and text analysis, and clearly show the public perception of the business environment. The empirical study found that the public perception of business environment depends on not only the four dimensions of business environment, but also the influence of public opinion that cannot be ignored. The public's low recognition of the business environment in Heilongjiang Province mainly includes backward economic development, serious brain drain, low government efficiency, imperfect policies, administrative law enforcement, regional climate and urban construction. In order to solve these problems, it is necessary to improve the high-standard market system to promote economic development, enhance the efficiency of government services, improve government policies, effectively enhance law enforcement, strengthen infrastructure construction and promote cultural innovation.

In order to develop continuously variable transmission (CVT) suited for electric vehicle (EV), a comparative analysis of the transmission used on EV is introduced in this paper. To solve the problems of traditional CVT used for EV, a newly designed electric CVT (ECVT) is proposed. The final drive ratio, speed ratio range of variator and hydraulic system of ECVT are redesigned for improving the transmission efficiency. Considering that the permanent magnet synchronization traction motor (PMSTM) of EV has an ideal driving characteristic (Constant torque at low speed, constant power at high speed) and wider high efficiency area compared with gasoline engine, the speed ratio control strategy of ECVT is studied again for improving the vehicle driving range and better meeting the requirements of driver. Finally, a simulation test system is fabricated for evaluating the battery energy consumption of an EV equipped with ECVT and single-speed transmission (SST) under constant speed and road drive cycle. The simulation results show that the ECVT proposed can extend the endurance mileage of EV at the speed of 20 to 90km/h, and improve the acceleration performance from 0 to 50km/h. The EV equipped with ECVT showed more advantages compared with SST in urban conditions.

Abstract Background As one of the major diagnostic criteria in Musculoskeletal Infection Society, the microbiological diagnosis of periprosthetic joint infection (PJI) performed by analyzing periprosthetic tissue culture is recommended. The goal of this study was to determine if methylene blue (MB) has antibacterial effects that might interfere with microbial culture in vitro. Methods Eight isolates of reference strains of Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hominis, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Streptococcus pyogenes, and Candida albicans were incubated appropriately on blood agar, China blue agar, or Sabouraud’s agar plates at 35 ℃. (Streptococci were cultured in a CO2-rich atmosphere.) Each bacterial suspension was formed by 50-fold dilution before the test MB was added. For each strain, bacterial suspension was divided into 3 groups (5 samples each) exposed either MB 0.1%, MB 0.05% or sterile non-bacteriostatic 0.45% saline. The antimicrobial property of MB was determined by measuring the bacterial density on agar plates incubated for 24 h and comparing it with controls unexposed to MB. Results Exposure to MB 0.1% or MB 0.05% negatively affected microbial viability in vitro. Of the diluted form of MB exposure, reference strains of S. hominis and A. baumannii resulted in fewer colony-forming units compared with the sterile saline control. MB concentration was significantly negatively correlated with CFU counts of S. hominis and A. baumannii strains. The antibacterial property of MB 0.1% or MB 0.05% appears to affect the ability to culture the organism in in vitro assays. Conclusion MB 0.1% or MB 0.05% has strong antimicrobial activities against some commonly encountered bacterial strains in PJI in vitro. To further evaluate its potential antibacterial usefulness in clinical applications, the next studies are needed to assess the ability of MB to affect the ability to culture the pathogens in vivo, especially in periprosthetic tissue.

Abstract Background This study aimed to investigate the effects of LINC00240/miR-155/Nrf2 axis on trophoblast function and macrophage polarization in the pathogenesis of preeclampsia. Methods Bindings between LINC00240, miR-155 and Nrf2 were validated by dual luciferase reporter assay or RNA-immunoprecipitation. Cell proliferation, migration, invasion, and pyroptosis were detected by CCK-8, clone formation, wound healing, Transwell system, and flow cytometry, respectively. Macrophage polarization was tested by flow cytometry. The expression levels of LINC00240, miR-155, Nrf2, and oxidative stress and pyroptosis-related markers in in vitro and in vivo preeclampsia models were analyzed by qPCR, western blot, or ELISA assays. Blood pressure, urine protein levels, liver and kidney damages, and trophoblast markers in placenta tissues were further studied in vivo. Results Placenta tissues from preeclampsia patients and animals showed decreased LINC00240 and Nrf2 and increased miR-155 expression levels, and the decreased M2 macrophage polarization. LINC00240 directly bound and inhibited expression of miR-155, which then inhibited oxidative stress-induced pyroptosis, promoting proliferation, migration and invasion abilities of trophoblasts, and M2 macrophage polarization. Inhibition of miR-155 led to increased Nrf2 expression and similar changes as LINC00240 overexpression in trophoblast function and macrophage polarization. Overexpression of LINC00240 in in vivo preeclampsia model decreased blood pressure, urine protein, liver and kidney damages, increased fetal weight and length, and induced trophoblast function and M2 macrophage polarization. Conclusion LINC00240 inhibited symptoms of preeclampsia through regulation on miR-155/Nrf2 axis, which suppressed oxidative stress-induced pyroptosis to improve trophoblast function and M2 macrophage polarization. LINC00240 could be a potential therapeutic target for preeclampsia.

Fluorescence in situ hybridization (FISH) is a powerful cytogenetic method used to precisely detect and localize nucleic acid sequences. This technique is proving to be an invaluable tool in medical diagnostics and has made significant contributions to biology and the life sciences. However, the number of cells is large and the nucleic acid sequences are disorganized in the FISH images taken using the microscope. Processing and analyzing images is a time-consuming and laborious task for researchers, as it can easily tire the human eyes and lead to errors in judgment. In recent years, deep learning has made significant progress in the field of medical imaging, especially the successful application of introducing the attention mechanism. The attention mechanism, as a key component of deep learning, improves the understanding and interpretation of medical images by giving different weights to different regions of the image, enabling the model to focus more on important features. To address the challenges in FISH image analysis, we combined medical imaging with deep learning to develop the SEAM-Unet++ automated cell contour segmentation algorithm with integrated attention mechanism. The significant advantage of this algorithm is that it improves the accuracy of cell contours in FISH images. Experiments have demonstrated that by introducing the attention mechanism, our method is able to segment cells that are adherent to each other more efficiently.

Abstract Purpose Our previous studies have suggested that the first trimester fasting plasma glucose (FPG) level is associated with gestational diabetes mellitus (GDM) and is a predictor of GDM. The aim of the present study was to provide valuable insights into the accuracy of the first trimester FPG level in the screening and diagnosis of GDM in southern China. Methods This retrospective study included pregnant women who had their first trimester FPG level recorded at 9–13+6 weeks and underwent screening for GDM using the 2-h 75 g oral glucose tolerance test (OGTT) between the 24th and 28th gestational weeks. Differences between the GDM and non-GDM groups were assessed by Student’s t test and the chi-squared test according to the nature of the variables. A restricted cubic spine was used to explore the relationship between the first trimester FPG level and the odds ratio (OR) of GDM in pregnant women. Cut-off values of first trimester FPG were determined using receiver operating characteristic (ROC) curves and the area under the curve (AUC), and 95% confidence intervals (CIs), the positive predictive value (PPV) and the negative predictive value (NPV) were calculated. Results The medical records of 28,030 pregnant women were analysed, and 4,669 (16.66%) of them were diagnosed with GDM. The average first trimester FPG level was 4.62 ± 0.37 mmol/L. The OR of GDM increased with increasing first trimester FPG levels and with a value of first trimester FPG of approximately 4.6 mmol/L, which was equal to 1 (Chi-Square = 665.79, P

Abstract Background The association between maternal obesity and preterm birth remains controversial and inconclusive, and the effects of gestational diabetes mellitus (GDM) and preeclampsia (PE) on the relationship between obesity and preterm birth have not been studied. We aimed to clarify the relationship between prepregnancy body mass index (BMI) and the phenotypes of preterm birth and evaluate the mediation effects of GDM and PE on the relationship between prepregnancy BMI and preterm birth. Methods We conducted a prospective cohort study of 43,056 women with live singleton births from 2017 through 2019. According to the WHO International Classification, BMI was classified as underweight (BMI

Abstract. Background:. Gestational weight gain (GWG) is associated with the risk of gestational diabetes mellitus (GDM). However, the effect of weight gain in different trimesters on the risk of GDM is unclear. This study aimed to evaluate the effect of GWG on GDM during different trimesters. Methods:. A birth cohort study was conducted from 2017 to 2020 in Shenzhen, China. In total, 51,205 participants were included comprising two models (early pregnancy model and middle pregnancy model). Gestational weight (kg) was measured at each prenatal clinical visit using a standardized weight scale. Logistic regression analysis was used to assess the risk of GDM. Interaction analysis and mediation effect analysis were performed in the middle pregnancy model. Results:. In the early pregnancy model, the risk of GDM was 0.858 times lower (95% confidence interval [CI]: 0.786, 0.937) with insufficient GWG (iGWG) and 1.201 times higher (95% CI: 1.097, 1.316) with excessive GWG after adjustment. In the middle pregnancy model, the risk of GDM associated with iGWG increased 1.595 times (95% CI: 1.418, 1.794) after adjustment; for excessive GWG, no significant difference was found (P = 0.223). Interaction analysis showed no interaction between GWG in early pregnancy (GWG-E) and GWG in middle pregnancy (GWG-M) (F = 1.268; P = 0.280). The mediation effect analysis indicated that GWG-M plays a partial mediating role, with an effect proportion of 14.9%. Conclusions:. eGWG-E and iGWG-M are associated with an increased risk of GDM. Strict control of weight gain in early pregnancy is needed, and sufficient nutrition should be provided in middle pregnancy.

Summary: The cellular and molecular actions of general anesthetics to induce anesthesia state and also cellular signaling changes for subsequent potential “long term” effects remain largely elusive. General anesthetics were reported to act on voltage-gated ion channels and ligand-gated ion channels. Here we used single-cell RNA-sequencing complemented with whole-cell patch clamp and calcium transient techniques to examine the gene transcriptome and ion channels profiling of sevoflurane and propofol, both commonly used clinically, on the human fetal prefrontal cortex (PFC) mixed cell cultures. Both propofol and sevoflurane at clinically relevant dose/concentration promoted “microgliosis” but only sevoflurane decreased microglia transcriptional similarity. Propofol and sevoflurane each extensively but transiently (

Background Limited data are available for postpartum hypertension prediction after preeclampsia. Methods and Results We examined the association between maternal serum chemerin levels in patients with preeclampsia and blood pressure (BP) levels after delivery in a prospective birth cohort of 15 041 singleton pregnant women. A total of 310 cases among 322 patients with preeclampsia (follow‐up rate, 96.3%) were followed up during a mean 2.8 years after delivery. Compared with matched uncomplicated controls (n=310), serum chemerin measured at ≈35 gestational weeks was significantly increased in preeclampsia (171.8±49.2 versus 140.2±53.5 ng/mL; P

Abstract Background The low incidence of primary mediastinal seminomas has precluded the development of clinical trials on mediastinal seminomas. We investigated the clinicopathologic characteristics, prognosis of patients with primary mediastinal seminomas as well as the efficiency of nonsurgical treatments compared with treatments containing surgery. Methods We retrospectively collected data on the clinicopathologic characteristics, treatments, toxicities, and survival of 27 patients from a single center between 2000 and 2018. Patients were divided into two groups according to whether they received operation. Survivals were assessed using the Kaplan–Meier method. Univariate analysis was performed using the log-rank test. Results The median age was 28 (13–63) years. The most common symptoms were chest pain (29.6%), cough (25.9%), and dyspnea (22.2%). There were 13 and 14 patients in surgery and non-surgery group. Patients in the non-surgical group were more likely to be with poor performance scores (100% vs. 76.9%) and disease invaded to adjacent structures (100% vs. 76.9%) especially great vessels (100% vs. 46.2%).The median follow-up period was 32.23 (2.7–198.2) months. There was no significant difference of overall survival (5-year 100% vs. 100%), cancer-specific survival (5-year 100% vs. 100%), local regional survival (5-year 91.7% vs. 90.0%, p = 0.948), distant metastasis survival (5-year 90.9% vs. 100.0%, p = 0.340) and progression-free survival (82.5% vs. 90.0%, p = 0.245) between patients with and without surgery. Conclusions Primary mediastinal seminoma was with favorable prognosis, even though frequently invasion into adjacent structures brings difficulties to surgery administration. Chemoradiotherapy is an alternative treatment with both efficacy and safety.

This paper proposes a modified model predictive control method with the virtual model (VM-MPC) to generate a virtual reference of the position loop. The dynamic deviation is introduced into the virtual reference as a position advance. Applying this virtual reference as the input of position controllers, the dynamic response is greatly improved without changing the gain of position controllers. Therefore, both the dynamic response and robustness of the position loop are improved when the response delay of the speed loop is uncertain. In order to reduce the influence of model mismatch on model predictive control, instead of the actual feedback, a virtual model feedback of the expected position response is used. With this approach, control parameters of VM-MPC are optimized offline to obtain the fast position response without overshoot. A model compensator is proposed to reduce the mismatch between the virtual model and the real system. The effectiveness and feasibility of the proposed method are verified by simulation and experiment results.

Summary: Lysosomal amino acid accumulation is implicated in several diseases, but its role in insulin resistance, the central mechanism to type 2 diabetes and many metabolic diseases, is unclear. In this study, we show the hepatic expression of lysosomal membrane protein solute carrier family 7 member 14 (SLC7A14) is increased in insulin-resistant mice. The promoting effect of SLC7A14 on insulin resistance is demonstrated by loss- and gain-of-function experiments. SLC7A14 is further demonstrated as a transporter resulting in the accumulation of lysosomal γ-aminobutyric acid (GABA), which induces insulin resistance via inhibiting mTOR complex 2 (mTORC2)’s activity. These results establish a causal link between lysosomal amino acids and insulin resistance and suggest that SLC7A14 inhibition may provide a therapeutic strategy in treating insulin resistance-related and GABA-related diseases and may provide insights into the upstream mechanisms for mTORC2, the master regulator in many important processes.

We completed a systematic review of Takotsubo syndrome (TTS) cases reported during the coronavirus disease 2019 (COVID-19) pandemic and performed clustering and feature importance analysis and statistical testing for independence on the demographic, clinical, and imaging parameters. Compared with the data before the COVID-19 pandemic, TTS was increasingly diagnosed in physical stress (mostly COVID-19 pneumonia)–triggered male patients without psychiatric/neurologic disorders, warranting further investigation to establish new reference criteria to improve diagnostic specificity. In clustering analysis, sex and inpatient mortality primarily contributed to the automated classification of the TTS. Both sex and inpatient mortality had essential correlations with COVID-19 infection/pneumonia. There is effect modification of sex on outcomes in patients with COVID-19 infection and TTS, with male patients having significantly worse inpatient mortality. Meanwhile, significantly more male patients with TTS were classified as high risk according to International Takotsubo Registry prognostic scores, suggesting that male COVID-19/TTS survivors will likely have worse long-term outcome.

Introduction Atherosclerosis is the leading cause of cardiovascular disease (CVD), which is one of the most common causes of morbidity and mortality worldwide. Lipid accumulation and inflammation play a crucial role in the pathogenesis of atherosclerosis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are an emerging lipid-lowering agent reported as a potential anti-inflammation effect in the prevention of CVD. However, the anti-inflammatory effect is still elusive. Therefore, a systematic review and meta-analysis is needed to analyse the anti-inflammatory effect of PCSK9 inhibitors on atherosclerosis in practice.Methods and analysis This protocol was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. We will include double-blind, randomised controlled trials that reported changes in the levels of inflammatory markers, with an intervention arm of PCSK9 inhibitors and a treatment duration of more than 2 weeks. The following databases will be mainly searched from 1 January 2003 to the formal search date: PubMed, Embase, Web of Science and the Cochrane Central Register of Controlled Trials. The primary aim is to assess the effect of PCSK9 inhibitors on inflammatory markers, including circulating inflammatory markers such as C-reactive protein, high-sensitivity C-reactive protein, white cell counts, IL-1β, IL-6 and TNF-α and local inflammatory markers such as the most diseased segment target-to-background ratio of the index vessel in adult patients with atherosclerosis. We will assess the quality of evidence, heterogeneity and report bias following the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions.Ethics and dissemination Due to the systematic review being based on published studies, no ethics approval is required. The study results will be presented at international conferences and published in a peer-reviewed journal.PROSPERO registration number CRD42022297710.

The resistant cells that proliferate after radiotherapy and chemotherapy are primarily tumor stem cells with high stem marker expression, and their presence is the primary cause of tumor dispersion. The Wnt signaling receptor Frizzled family receptor 7 (FZD7) is linked to the maintenance of stem cell features as well as cancer progression. Frizzled-7 (FZD7), a key receptor for Wnt/-catenin signaling, is overexpressed in TNBC, suggesting that it could be a viable target for cancer therapy. We employed bioinformatics to find the best-scoring peptide, chemically synthesized FZD7 epitope antigen, and binding toll-like receptor 7 agonists (T7). Under GMP conditions, peptides for vaccines were produced and purified (>95%). In vivo and vitro tests were used to assess tumor cell inhibition. In vitro, the FZD7-T7 vaccination can boost the maturity of BMDC cells considerably. In mice, the FZD7 - T7 vaccine elicited the greatest immunological response. Significant tumor development inhibition was seen in BALB/c mice treated with FZD7 - T7 in prevention experiments (P < 0.01). Multiple cytokines that promote cellular immune responses, such as interferon (IFN)-γ (P < 0.05), interleukin (IL)-12 (P < 0.05), and IL-2 (P < 0.01), were shown to be considerably elevated in mice inoculated with FZD7- T7. Furthermore, we evaluated safety concerns in terms of vaccine composition to aid in the creation of successful next-generation vaccines. In conclusion, the FZD7-T7 vaccine can activate the immune response in vivo and in vitro, and play a role in tumor suppression. Our findings reveal a unique tumor-suppressive role for the FZD7 peptide in TNBC.

The Datong and Xiaotong rivers are karst tributaries in the upper Yangtze River drainage and represent considerable habitat diversity that contributes to high fish diversity and rich fishery resources in the two rivers. During the few decades, fish resources have abruptly declined due to overfishing, water pollution and habitat degradation. In order to further strengthen conservation and restoration of fish resources and provide scientific support for fishery management in these rivers, the temporal and spatial dynamics of fish assemblage in the Datong and Xiaotong rivers were investigated in the present study. A total of 45 species were captured at 30 sample sites during four surveys conducted from March 2016 to January 2017. Species diversity and richness both increased from upstream to downstream in the two rivers. The fish assemblages significantly differed between river reaches, while did not differ in significantly between 4 months. The spatial variations in the abundance of Rhynchocypris oxycephalus, Zacco platypus, Triplophysa bleekeri, Sinogastromyzon szechuanensis, Platysmacheilus nudiventris, Sinibrama taeniatus, Saurogobio gymnocheilus, Pseudorasbora parva, Pseudobagrus truncates and Opsariichthys bidens were considered to contribute most to the spatial pattern of fish assemblages. The lack of a temporal pattern of the fish assemblage in the rivers might be attributed to ecological habits of short-distance migration and diversified mesohabitats with riffles and pools for fish spawning, feeding or overwintering within a very short river range. Our results suggest the spatio-temporal dynamics of fish assemblages is highly adapted to the habitat characteristics in the two karst rivers. We recommend that fish conservation of these tributaries be focused on the mesohabitats, particularly the many pools and riffles.

BackgroundActin-related protein 2/3 complex subunit 5 (ARPC5) is one of the members of actin-related protein 2/3 complex and plays an important role in cell migration and invasion. However, little is known about the expression pattern, prognosis value, and biological function of ARPC5 in pan-cancer. Thus, we focus on ARPC5 as cut point to explore a novel prognostic and immunological biomarker for cancers.MethodsThe public databases, including TCGA, GTEx, and UCEC, were used to analyze ARPC5 expression in pan-cancer. The Human Protein Atlas website was applied to obtain the expression of ARPC5 in different tissues, cell lines, and single-cell types. Univariate Cox regression analysis and Kaplan–Meier analysis were used to explore the prognosis value of ARPC5 in various cancers. Spearman’s correlation analysis was performed to investigate the association between ARPC5 expression and tumor microenvironment scores, immune cell infiltration, immune-related genes, TMB, MSI, RNA modification genes, DNA methyltransferases, and tumor stemness. Moreover, qPCR, Western blot, and immunohistochemistry were carried out to examine the differential expression of ARPC5 in HCC tissues and cell lines. CCK8, EdU, flow cytometry, wound-healing assays, and transwell assays were conducted to explore its role in tumor proliferation, apoptosis, migration, and invasion among HCC cells.ResultsARPC5 expression was upregulated in most cancer types and significantly associated with worse prognosis in KIRC, KIRP, LGG, and LIHC. mRNA expression of ARPC5 showed low tissue and cell specificity in normal tissues, cell lines, and single-cell types. ARPC5 expression was positively correlated with the tumor microenvironment scores, immune infiltrating cells, immune checkpoint–related genes in most cancers. ARPC5 in STAD and BRCA was positively associated with TMB, MSI, and neoantigens. We also discovered that ARPC5 was correlated with the expression of m1A-related genes, m5C-related genes, m6A-related genes, and DNA methyltransferases. In experiment analyses, we found that ARPC5 was significantly highly expressed in HCC tissues and HCC cells. Functionally, silencing ARPC5 dramatically decreased proliferation, migration, and invasion ability of HCC cells.ConclusionsARPC5 expression affects the prognosis of multiple tumors and is closely correlated to tumor immune infiltration and immunotherapy. Furthermore, ARPC5 may function as an oncogene and promote tumor progression in HCC.

Abstract Aims Acute pulmonary disorders are known physical triggers of takotsubo syndrome (TTS). This study aimed to investigate prevalence of acute pulmonary triggers in patients with TTS and their impact on outcomes. Methods and results Patients with TTS were enrolled from the International Takotsubo Registry and screened for triggering factors and comorbidities. Patients were categorized into three groups (acute pulmonary trigger, chronic lung disease, and no lung disease) to compare clinical characteristics and outcomes. Of the 1670 included patients with TTS, 123 (7%) were identified with an acute pulmonary trigger, and 194 (12%) had a known history of chronic lung disease. The incidence of cardiogenic shock was highest in patients with an acute pulmonary trigger compared with those with chronic lung disease or without lung disease (17% vs. 10% vs. 9%, P = 0.017). In‐hospital mortality was also higher in patients with an acute pulmonary trigger than in the other two groups, although not significantly (5.7% vs. 1.5% vs. 4.2%, P = 0.13). Survival analysis demonstrated that patients with an acute pulmonary trigger had the worst long‐term outcome (P = 0.002). The presence of an acute pulmonary trigger was independently associated with worse long‐term mortality (hazard ratio 2.12, 95% confidence interval 1.33–3.38; P = 0.002). Conclusions The present study demonstrates that TTS is related to acute pulmonary triggers in 7% of all TTS patients, which accounts for 21% of patients with physical triggers. The presence of acute pulmonary trigger is associated with a severe in‐hospital course and a worse long‐term outcome.

Background: Patients with non-valvular atrial fibrillation (NVAF) need prophylactically antithrombotic therapies to reduce the risk of stroke. We hypothesized that the prognostic benefits of prophylactic antithrombotic therapies outweighed the bleeding risk among very elderly (≥85 years old) patients. Methods: We analyzed clinical characteristics and outcomes of patients with NVAF in different age groups who had received different prophylactic antithrombotic therapies. We enrolled 3895 consecutive NVAF patients in the Macau Special Administrative Region (Macau SAR) of China from January 1, 2010, to December 31, 2018. Among 3524 patients [including 1252 (35.53%) very elderly patients] who completed the entire study, 2897 (82.21%) patients had a CHA2DS2-VASc score ≥ 2, 2274 (64.53%) had HAS-BLED score

Abstract Spatial transcriptomic and proteomic technologies have provided new opportunities to investigate cells in their native microenvironment. Here we present Giotto, a comprehensive and open-source toolbox for spatial data analysis and visualization. The analysis module provides end-to-end analysis by implementing a wide range of algorithms for characterizing tissue composition, spatial expression patterns, and cellular interactions. Furthermore, single-cell RNAseq data can be integrated for spatial cell-type enrichment analysis. The visualization module allows users to interactively visualize analysis outputs and imaging features. To demonstrate its general applicability, we apply Giotto to a wide range of datasets encompassing diverse technologies and platforms.

The phase-shifted full-bridge (PSFB) converter has been widely used in power supply modules due to its simple control and high output power. However, with the market’s increasing demand for higher power sources, the PSFB converter needs to face challenges in increasing its output power level. Compared to redesigning a larger power module or a larger single converter, it will be more cost-effective to achieve a higher power output by paralleling the existing converters. However, due to the manufacturing differences in circuit components, the output imbalance in parallel PSFB converter systems may damage the power modules. Thus, the influence of differences in circuit components is analyzed in this paper, and it is found that the leakage inductance and transformer ratio are the main factors resulting in errors in current sharing control. Consequently, a dynamic hybrid compensator (DHC) is proposed in this paper, that can significantly reduce the error in current sharing control via the compensation of the duty cycle of a slave module. Furthermore, the DHC is verified on an 800 W two-phase PSFB converter, which shows that even when the difference in components is as large as 20%, the proposed method can still reduce the error in current sharing control to less than 2% under both half and full load conditions.

Many microbes accumulate energy storage molecules such as triglycerides (TAG) and starch during nutrient limitation. In eukaryotic green algae grown under nitrogen-limiting conditions, triglyceride accumulation is coupled with chlorosis and growth arrest. In this study, we show that reactive oxygen species (ROS) actively accumulate during nitrogen limitation in the microalga Chlorella sorokiniana. Accumulation of ROS is mediated by the downregulation of genes encoding ROS-quenching enzymes, such as superoxide dismutases, catalase, peroxiredoxin, and glutathione peroxidase-like, and by the upregulation of enzymes involved in generating ROS, such as NADPH oxidase, xanthine oxidase, and amine oxidases. The expression of genes involved in ascorbate and glutathione metabolism is also affected under this condition. ROS accumulation contributes to the degradation of monogalactosyl diacylglycerol (MGDG) and thylakoid membrane remodeling, leading to chlorosis. Quenching ROS under nitrogen limitation reduces the degradation of MGDG and the accumulation of TAG. This work shows that ROS accumulation, membrane remodeling, and TAG accumulation under nitrogen limitation are intricately linked in the microalga C. sorokiniana. [ABSTRACT FROM AUTHOR]

Online parameter estimation of permanent magnet synchronous machines is critical for improving their control performance and operational reliability. This paper provides an overview of the recent achievements of online parameter estimation of PMSMs with examples. The critical issues in parameter estimation are firstly analysed, especially the rank-deficient issue and inverter nonlinearities. Then, the state-of-the-art online parameter estimation modelling techniques are reviewed and assessed. Finally, some typical applications and examples are outlined, e.g. estimation of mechanical parameters, improvement of sensored and sensorless control performance, thermal condition monitoring, and fault diagnosis, together with future research trends.

Nonideal switching characteristics of voltage source inverter (VSI) will result in distortions in both phase currents and reference voltages of a permanent magnet synchronous machine (PMSM) drive system, which will also consequently introduce ripples into the output speed and shaft torque, and result in a performance deterioration in the state observation control. To solve this issue, a method of directly extracting and compensating the nonlinear voltage disturbance due to VSI nonlinearity employed in PMSM drives is proposed in this paper. Firstly, the distorted voltage due to VSI nonlinearity is directly extracted via a harmonic separation scheme, which can be easily compensated by a proportional integral controller afterwards. Since both 6th harmonic and DC terms of dq-axis distorted voltages due to VSI nonlinearity are well compensated, the proposed method shows sufficiently good performance under both $i_{d}=0$ and maximum torque per ampere controls ( $i_{d} < 0$ ), as verified on two prototype PMSMs being salient pole and non-salient pole, respectively, both developed for a low-speed rotary actuator. In addition, the application of proposed method to state observation controls such as the model-based sensorless control and the deadbeat predictive current control, is finally investigated. Test results manifest that the proposed method can effectively improve the accuracy of observed rotor position/speed, and the ability of current tracking.

The triplet-based knowledge in large-scale knowledge bases is most likely lacking in structural logic and problematic of conducting knowledge hierarchy. In this paper, we introduce the concept of metaknowledge to knowledge engineering research for the purpose of structural knowledge construction. Therefore, the Metaknowledge Extraction Framework and Document Structure Tree model are presented to extract and organize metaknowledge elements (titles, authors, abstracts, sections, paragraphs, etc.), so that it is feasible to extract the structural knowledge from multi-modal documents. Experiment results have proved the effectiveness of metaknowledge elements extraction by our framework. Meanwhile, detailed examples are given to demonstrate what exactly metaknowledge is and how to generate it. At the end of this paper, we propose and analyze the task flow of metaknowledge applications and the associations between knowledge and metaknowledge.

Abstract Background A systematic review and meta-analysis was performed to compare the clinicopathological features and survival outcomes between sarcomatoid variant (SV)-urothelial carcinoma of the bladder (UCB) and conventional UCB (C-UCB). Methods A comprehensive search of PubMed, Embase, and Cochrane Library was performed. Endpoints included clinicopathological features and survival outcomes (overall survival [OS], cancer-specific survival [CSS], and progression-free survival [PFS]). The survival benefits of neoadjuvant chemotherapy (NAC) or adjuvant chemotherapy (AC) for SV-UCB also have been studied. Results A total of 8 observational studies were included. Patients with SV-UCB had a higher rate of ≥ stage pT3 (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.64–2.59; p

Carbon materials reinforced copper matrix composites with excellent mechanical properties, high thermal conductivity (TC) and suitable coefficient of thermal expansion (CTE) are expected to meet the urgent need for the thermal management materials with structural stability and efficient heat dissipation in civil and military fields. In this work, the tungsten-copper (W-Cu) composite coating was deposited on the graphite flakes (GFs) by the impregnation-reduction and ultrasonic-assisted electroless plating. Meanwhile, the W-Cu coated GFs reinforced Cu matrix composites (GFs(W-Cu)/Cu) were also prepared by the vacuum hot-pressing sintering. Based on the microstructure and surface analysis, the interfacial bonding has changed from the simple mechanical connection to the mechanical-metallurgical synergy. As for the three-point bending and uniaxial tensile tests, the largest in-plane, through-plane flexural strength and tensile strength of the GFs(W-Cu)/Cu composite can achieve the values of 189.6 ± 3.8, 172.3 ± 4.2 and 91.9 ± 2.6 MPa, respectively. Among the GFs(W-Cu)/Cu composites, the ultrahigh in-plane TC and lowest through-plane CTE can reach 929.8 ± 5.0 Wm−1K−1 and 6.3 ± 0.2 ppmK−1 respectively, and the better thermal response rate can be 0.67 °C·s−1. In conclusion, an effective way to develop the structural and functional integrated carbon-based thermal management materials can be provided.

BackgroundThis study determined the predictive value of CRMP4 promoter methylation in prostate tissues collected by core needle biopsies for a postoperative upgrade of Gleason Score (GS) to ≥8 in patients with low-risk PCa.MethodA retrospective analysis of the clinical data was conducted from 631 patients diagnosed with low-risk PCa by core needle biopsy at multiple centers and then underwent Radical Prostatectomy (RP) from 2014-2019. Specimens were collected by core needle biopsy to detect CRMP4 promoter methylation. The pathologic factors correlated with the postoperative GS upgrade to ≥8 were analyzed by logistic regression. The cut-off value for CRMP4 promoter methylation in the prostate tissues collected by core needle biopsy was estimated from the ROC curve in patients with a postoperative GS upgrade to ≥8.ResultMultivariate logistic regression showed that prostate volume, number of positive cores, and CRMP4 promoter methylation were predictive factors for a GS upgrade to ≥8 (OR: 0.94, 95% CI: 0.91-0.98, P=0.003; OR: 3.16, 95% CI: 1.81-5.53, P18.00%, the low-risk PCa patients were more likely to escalate to high-risk patients. The predictive sensitivity and specificity were 86.9% and 98.8%, respectively. The area under the ROC curve (AUC) was 0.929 (95% CI: 0.883-0.976; P18.0% and postoperative GS upgrade to ≥8 than in patients without an upgrade (P ≤ 0.002).ConclusionA CRMP4 promoter methylation rate >18.00% in prostate cancer tissues indicated that patients were more likely to escalate from low-to-high risk after undergoing an RP. We recommend determining CRMP4 promoter methylation before RP for low-risk PCa patients.

Abstract Background Spacer complications may affect final clinical outcome of the two-stage approach in periprosthetic joint infection (PJI) patients. This study aimed to investigate clinical outcomes and complications of augmented antibiotic-loaded cement spacer in PJI patients with acetabular bone defect. Methods Data on PJI patients with acetabular bone defect receiving two-stage revision from January 2009 to December 2016, in our hospital were retrospectively reviewed. Screw-cement-shell was used to improve the stability of the hip with acetabular wall defect. Handmade acetabular spacer could prevent femoral spacer entering into pelvis in patients with acetabular internal wall defect. A total of 26 patients (11 males and 15 females) were included in the current study. Their mean age was 46.7 ± 15.4 years old. Clinical outcomes and complications were measured. Results Twenty-one of total 26 hips (21/26, 80.8%) showed positive cultures and 15/26 (57.7%) samples were cultured with staphylococcus. Of enrolled patients, 5/26 (19.2%) developed mixed infection. There was one patient (3.8%) with spacer dislocation and two (7.7%) with spacer fracture. One patient developed acute PJI 5 years after the second-stage revision, so overall success rate among these patients was 96.2%. Differences in Paprosky classifications before the first and second stage did not reach significant level (p > 0.05). Hip Harris score was raised from 40.9 ± 14.0 to 81.2 ± 11.2 (p < 0.05). Conclusions Augmented antibiotic-loaded cement spacer could achieve satisfactory clinical outcomes in PJI patients with acetabular bone defect. It provided joint mobility, increased additional joint stability, and decreased iatrogenic bone defect caused by acetabular wear.

Aiming to suppress the influence of uncertain disturbances in the drive control of permanent magnet synchronous machines (PMSM), such as the parameter uncertainties and load disturbance, a robust anti-interference control for the angular position tracking control of a PMSM servo system has been proposed in this paper. During the position tracking, uncertain system disturbances being regarded as a lumped unknown term will be online observed by a nonlinear disturbance observer (NDOB), of which the influence will consequently be counteracted by a robust backstepping compensator (RBC). The asymptotical stability of proposed control scheme is analyzed and designed according to the Lyapunov stability criterion, and its convergence against the system uncertain disturbance is verified on a prototype PMSM servo platform and shows good performance in rotor angular position tracking and anti-interference.

Abstract Background Cultivated rice consists of two subspecies, Indica and Japonica, that exhibit well-characterized differences at the morphological and genetic levels. However, the differences between these subspecies at the transcriptome level remains largely unexamined. Here, we provide a comprehensive characterization of transcriptome divergence and cis-regulatory variation within rice using transcriptome data from 91 accessions from a rice diversity panel (RDP1). Results The transcriptomes of the two subspecies of rice are highly divergent. Japonica have significantly lower expression and genetic diversity relative to Indica, which is likely a consequence of a population bottleneck during Japonica domestication. We leveraged high-density genotypic data and transcript levels to identify cis-regulatory variants that may explain the genetic divergence between the subspecies. We identified significantly more eQTL that were specific to the Indica subspecies compared to Japonica, suggesting that the observed differences in expression and genetic variability also extends to cis-regulatory variation. Conclusions Using RNA sequencing data for 91diverse rice accessions and high-density genotypic data, we show that the two species are highly divergent with respect to gene expression levels, as well as the genetic regulation of expression. The data generated by this study provide, to date, the largest collection of genome-wide transcriptional levels for rice, and provides a community resource to accelerate functional genomic studies in rice.

Abstract Background The most convenient circulating tumor cells (CTCs) identification method is direct analysis of cells under bright field microscopy by which CTCs can be comprehensive studied based on morphology, phenotype or even cellular function. However, universal cell markers and a standard tumour cell map do not exist, thus limiting the clinical application of CTCs. Results This paper focuses on an automatic and convenient negative depletion strategy for circulating tumour cell identification under bright field microscopy. In this strategy, immune microparticles (IMPs) are applied to negatively label white blood cells rather than the tumour cells, such that tumour cells can be directly distinguished under brightfield of the microscopy. In this way, all of the heterogeneous tumour cells and their phenotype properties can be retained for further cancer-related studies. In addition, a wedge-shaped microfluidic chip is constructed for heterogeneous CTC pre-purification and enrichment by size, thus significantly decreasing the interference of haematological cells. Additionally, all cell treatments are processed automatically, and the tumour cells can be rapidly counted and distinguished via customized cell analytical software, showing high detection efficiency and automation. This IMPs based negative cell labelling strategy can also be combined with other classic cell identification methods, thus demonstrating its excellent compatibility. Conclusion This identification strategy features simple and harmless for tumour cells, as well as excellent accuracy and efficiency. And the low equipment demand and high automation level make it promise for extensive application in basic medical institutions.

Objective: Cancer stem cell is one of the important causes of tumorigenesis as well as a drug target in the treatment of malignant tumor. However, at present, there is no immune vaccine targeting these cells. Octamer-binding transcription factor 4 (OCT4), a marker of embryonic stem cells and germ cells, often highly expresses in the early stages of tumorigenesis and is therefore a good candidate for cancer vaccine development. Methods: To identify the optimal carrier and adjuvant combination, we chemically synthesized and linked three different OCT4 epitope antigens to a carrier protein, keyhole limpet hemocyanin (KLH), combined with Toll-like receptor 9 agonist (TLR9). Results: Immunization with OCT4-3 + TLR9 produced the strongest immune response in mice. In prevention assays, significant tumor growth inhibition was achieved in BABL/c mice treated with OCT4-3 + TLR9 (P < 0.01). Importantly, the results showed that cytotoxic T lymphocyte activity and the inhibition of tumor growth were enhanced in mice immunized with OCT4-3 combined with TLR9. Meanwhile, multiple cytokines [such as interferon (IFN)-γ (P < 0.05), interleukin (IL)-12 (P < 0.05), IL-2 (P < 0.01), and IL-6 (P < 0.05)] promoting cellular immune responses were shown to be greatly enhanced in mice immunized with OCT4-3 + TLR9. Moreover, we considered safety considerations in terms of the composition of the vaccines to help facilitate the development of effective next-generation vaccines. Conclusions: Collectively, these experiments demonstrated that combination therapy with TLR9 agonist induced a tumor-specific adaptive immune response, leading to the suppression of primary tumor growth in testis embryonic carcinoma.

Residual placenta is one of the common types of postpartum complications in clinical practice. Residual placenta is also the main and most common cause of late postpartum hemorrhage. This article proposes a spatial pyramid loop module, which solves the problem that the existing network structure cannot effectively extract the semantic information and category information in the image at the same time. The spatial pyramid structure is used to effectively extract the semantic information and category information. In addition, this article proposes to use cyclic convolutional network to realize the transfer function of information at different scales, and build it in the spatial pyramid structure to further strengthen the ability to extract semantic information and category information. This article proposes a feature fusion module to solve the impact of image classification network used in the base network in the existing network structure. The attention mechanism is used to achieve the effective fusion of high-dimensional features and low-dimensional features in the base network to reduce the influence of the base network, so as to better recover the recognition and prediction results. A semantic category loss function is proposed to supervise the categories of objects in images. This article builds it on the feature layer with the smallest scale, which not only increases the intermediate supervision to make the network fully converge, but also reduces the difficulty of extracting category information, and makes full use of the information transfer function of the cyclic convolutional network. This article introduces uncertainty information into the field of image segmentation to provide the accuracy of segmentation. For the purpose of uncertainty information, this article improves the network structure. At the same time for the image segmentation task, this article improves the Bayesian cross entropy loss function. The experiment verifies the necessity of improving the Bayesian crossover function in this article and the effectiveness of the conditional random field used in this article, and also verifies the effectiveness of the proposed semi-supervised learning method.