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Abstract Background The low live birth rate and difficult decision-making of the in vitro fertilization (IVF) treatment regimen bring great trouble to patients and clinicians. Based on the retrospective clinical data of patients undergoing the IVF cycle, this study aims to establish classification models for predicting live birth outcome (LBO) with machine learning methods. Methods The historical data of a total of 1405 patients undergoing IVF cycle were first collected and then analyzed by univariate and multivariate analysis. The statistically significant factors were identified and taken as input to build the artificial neural network (ANN) model and supporting vector machine (SVM) model for predicting the LBO. By comparing the model performance, the one with better results was selected as the final prediction model and applied in real clinical applications. Results Univariate and multivariate analysis shows that 7 factors were closely related to the LBO (with P

Abstract Disc cutters are essential for full-section hard-rock tunnel boring machines. The performance of these devices directly affects tunnel engineering costs and duration. This paper proposes a sinusoidal variable cross-section (VCS) cutter ring and design method and establishes a digital model. Rock-like materials are simulated with a finite element model, and the model validity is verified via rock simulation mechanics tests. A disc cutter rolling rock simulation model for a linear cutting machine is also established, and simulation tests are performed for single- and three-cutter rolling using sinusoidal VCSs and constant cross-section (CCS) cutter models, respectively. The stress and energy changes for the cutters and rock-like material damage area were compared via simulation, confirming that some sinusoidal VCS cutter rings do less work on rock-like materials and cause larger crushing areas under the same engineering parameters; therefore, these cutter rings have smaller specific energies. The sinusoidal VCS cutter ring performance is 7% greater than that of CCS on average under single-cutter simulation, and the intermediate cutter performance of the intermediate cutter is 9% greater than that of CCS on average under three-cutter simulation. Thus, sinusoidal VCS cutter rings offer improved rock damage performance, and further research and application of this technology will improve the working efficiency of tunnel boring machines.

BackgroundAdrenocortical carcinoma (ACC) is a rare malignant tumor that occurs in the adrenal cortex. It has a high degree of malignancy and comparatively poor overall prognosis. Surgery is the standard curative therapy for localized ACC patients. The combination regimen of etoposide, doxorubicin, cisplatin (EDP) plus mitotane has been considered as the standardized chemotherapy regimen for advanced ACC. However, new effective regimens are emerging for specific conditions in metastatic ACC.Case presentationWe report a case of a 66-year-old man diagnosed with metastatic ACC who had a large left adrenal mass (110 mm × 87 mm) and multiple metastases in both lungs. The patient was treated with EP and sintilimab for six cycles; anlotinib was introduced after the third cycle. Follow-ups after the second to fourth cycles found significantly reduced lung metastases with all imaging examinations indicating partial response (PR) status. The patient received maintenance therapy thereafter with sintilimab plus anlotinib. Until recently, the patient’s lung metastases and the left adrenal gland area mass (39mm × 29mm) have disappeared, and no disease progression has been observed. The progression-free survival of this patient has been extended to approximately 31 months, in sharp contrast to a median survival time of 12 months for majority of advanced ACC. The main adverse events during treatment were appetite loss and grade I myelosuppression and revealed only grade I hypertension and grade I hypothyroidism.ConclusionThis case highlights the remarkable response of our patient’s ACC to treatment with a novel combination of EP and sintilimab combined with anlotinib. Our findings suggest a safe and more effective combination therapeutic option for patients with adrenocortical carcinoma.

Context: Ultrasound (US) is the most economical and widely used method for detecting lesions in parathyroid regions. Identifying typically parathyroid adenomas as hypoechoic nodules with clear margins. However, 10 % of lesions exhibit atypical features, such as the dual concentric sign, and the cognition of them still needs to be improved. Objective: To promote understanding of clinical and histopathological features for parathyroid lesions with the dual concentric echo sign and to investigate its pathogenesis and methods for distinguishing from cervical lymph nodes to improve US diagnostic accuracy. Methods: Retrospectively, patients were categorized into three groups: Group 1, with 36 patients showing parathyroid lesions with dual concentric echo signs; Group 2, with 40 patients displaying classic hypoechoic parathyroid lesions; and Group 3, comprising 36 patients with identified lymph nodes, which were all examined from January 2018 to December 2019. The clinical data on demographics, clinical symptoms, serum levels, histopathologic findings, and US image characteristics were thoroughly reviewed. Results: According to the clinical data, no significant differences in demographics or lesion sizes were observed in Group 1 and Group 2 (p > 0.05). No significant variances were noted in biochemical markers, including PTH, T-25OHD, and ALP. However, a notable difference was identified in adjusted serum calcium levels, which were significantly lower in Group 1 compared to Group 2 (p

Objective The association of appendicular skeletal muscle mass (ASM), grip strength and fat-to-muscle ratio (FMR) and the progression of metabolic dysfunction-associated steatotic liver disease (MASLD) are not well known.Materials and methods This study included participants older than 40 years who underwent bioelectrical impedance assessment in Prevalence of Metabolic Diseases and Risk Factors in Shunde (SPEED-Shunde). We measured grip strength with an electronic grip strength metre. ASM and grip strength were adjusted by dividing body mass index (BMI). FMR was calculated as total fat mass to total muscle mass. Liver steatosis and liver fibrosis were evaluated by vibration-controlled transient elastography. Multifactorial logistic regression was used to analyse the relationship between ASM, grip strength, FMR, and MASLD or MASLD-associated liver fibrosis. We performed subgroup analyses according to sex, age and BMI. Interaction tests and linear trend tests were also conducted.Results This study included a total of 3277 participants. FMR was positively associated with MASLD (OR: 1.89, 95% CI: 1.66–2.15) and MASLD-associated liver fibrosis (OR: 1.70, 95% CI: 1.22–2.37). While ASM/BMI (OR: 0.59, 95% CI: 0.52–0.67) or grip strength/BMI (OR: 0.72, 95% CI: 0.66–0.78) were negatively associated with MASLD. Interactions were observed between ASM/BMI and age, grip strength and sex in MASLD, as well as FMR and MASLD-associated liver fibrosis.Conclusion In a middle-to-elderly aged population, FMR was positively associated with the risk of MASLD and MASLD-associated liver fibrosis, and muscle mass and grip strength were negatively associated with MASLD, rather than MASLD-associated liver fibrosis.

Background The expression and function of coexpression genes of M1 macrophage in cervical cancer have not been identified. And the CXCL9-expressing tumour-associated macrophage has been poorly reported in cervical cancer.Methods To clarify the regulatory gene network of M1 macrophage in cervical cancer, we downloaded gene expression profiles of cervical cancer patients in TCGA database to identify M1 macrophage coexpression genes. Then we constructed the protein–protein interaction networks by STRING database and performed functional enrichment analysis to investigate the biological effects of the coexpression genes. Next, we used multiple bioinformatics databases and experiments to overall investigate coexpression gene CXCL9, including western blot assay and immunohistochemistry assay, GeneMANIA, Kaplan-Meier Plotter, Xenashiny, TISCH2, ACLBI, HPA, TISIDB, GSCA and cBioPortal databases.Results There were 77 positive coexpression genes and 5 negative coexpression genes in M1 macrophage. The coexpression genes in M1 macrophage participated in the production and function of chemokines and chemokine receptors. Especially, CXCL9 was positively correlated with M1 macrophage infiltration levels in cervical cancer. CXCL9 expression would significantly decrease and high CXCL9 levels were linked to good prognosis in the cervical cancer tumour patients, it manifestly expressed in blood immune cells, and was positively related to immune checkpoints. CXCL9 amplification was the most common type of mutation. The CXCL9 gene interaction network could regulate immune-related signalling pathways, and CXCL9 amplification was the most common mutation type in cervical cancer. Meanwhile, CXCL9 may had clinical significance for the drug response in cervical cancer, possibly mediating resistance to chemotherapy and targeted drug therapy.Conclusion Our findings may provide new insight into the M1 macrophage coexpression gene network and molecular mechanisms in cervical cancer, and indicated that M1 macrophage association gene CXCL9 may serve as a good prognostic gene and a potential therapeutic target for cervical cancer therapies.

A critical event in the pathogenesis of kidney fibrosis is the transition of macrophages into myofibroblasts (MMT). Exosomes play an important role in crosstalk among cells in the kidney and the development of renal fibrosis. However, the role of myofibroblast-derived exosomes in the process of MMT and renal fibrosis progression remains unknown. Here, we examined the role of myofibroblast-derived exosomes in MMT and kidney fibrogenesis. In vitro, transforming growth factor-β1 stimulated the differentiation of kidney fibroblasts into myofibroblasts and promoted exosome release from myofibroblasts. RAW264.7 cells were treated with exosomes derived from myofibroblasts. We found purified exosomes from myofibroblasts trigger the MMT. By contrast, inhibition of exosome production with GW4869 or exosome depletion from the conditioned media abolished the ability of myofibroblasts to induce MMT. Mice treatment with myofibroblast-derived exosomes (Myo-Exo) exhibited severe fibrotic lesion and more abundant MMT cells in kidneys with folic acid (FA) injury, which was negated by TANK-banding kinase-1 inhibitor. Furthermore, suppression of exosome production reduced collagen deposition, extracellular matrix protein accumulation, and MMT in FA nephropathy. Collectively, Myo-Exo enhances the MMT and kidney fibrosis. Blockade of exosomes mediated myofibroblasts–macrophages communication may provide a novel therapeutic target for kidney fibrosis.

Background: Adipokines and inflammatory cytokines (ADICs) play important roles in type 2 diabetes mellitus (T2DM). This study aimed to compare the changes of ADIC levels (ΔADICs) in patients with newly diagnosed T2DM treated with different antihyperglycemic agents, and further investigate the impact of these changes on metabolic indices, β-cell function and insulin resistance (IR). Methods: Four hundred and sixteen patients with newly diagnosed T2DM from 25 centers in China randomly received 48-week intervention with exenatide, insulin or pioglitazone. Anthropometric and laboratory data, indices of β-cell function and IR, and levels of AIDCs, including interleukin-1 beta (IL-1β), interferon-gamma (IFN-γ), leptin, and fibroblast growth factor 21 (FGF21) were detected at baseline and the end of the study. Results: In total, 281 participants (68 % male, age: 50.3 ± 9.4 years) completed the study. After 48- week treatment, IL-1β and IFN-γ were significantly decreased with exenatide treatment (P

Taxonomic uncertainties of rare species often hinder effective prioritization for conservation. One such taxonomic uncertainty is the 90-year-old enigma of Fagus chienii. F. chienii was previously only known from the type specimens collected in 1935 in Pingwu County of Sichuan Province, China, and has long been thought to be on the verge of extinction. However, morphological similarities to closely related Fagus species have led many to question the taxonomic status of F. chienii. To clarify this taxonomic uncertainty, we used the newly collected samples to reconstruct a molecular phylogeny of Chinese Fagus species against the phylogenetic backbone of the whole genus using seven nuclear genes. In addition, we examined nine morphological characters to determine whether F. chienii is morphologically distinct from its putatively closest relatives (F. hayatae, F. longipetiolata, and F. lucida). Both morphological and phylogenetic analyses indicated that F. chienii is conspecific with F. hayatae. We recommended that F. chienii should not be treated as a separate species in conservation management. However, conservation strategies such as in situ protection and ex situ germplasm preservation should be adopted to prevent the peculiar “F. chienii” population from extinction.

Objective: Since coronary artery lesions (CALs) are the most severe complication of Kawasaki disease (KD), clinically speaking, early prediction of CALs is crucial. The authors aimed to investigate the predictive value of C-reactive protein (CRP) in predicting CALs in KD patients. Methods: KD patients were divided into the CALs group and the non-CALs group. The clinical and laboratory parameters were collected and compared. Multivariate logistic regression analysis was used to determine the independent risk factors of CALs. The receiver operating characteristic curve was applied to determine the optimal cut-off value. Results: 851 KD patients who met the inclusion criteria were studied, including 206 in the CALs group and 645 in the non-CALs group. Children in the CALs group had significantly higher CRP levels than the non-CALs group (p

The issue of aircraft icing poses a substantial threat to flight safety. In order to investigate more efficient anti-icing and de-icing technologies, a comparative analysis was conducted on the de-icing characteristics of three types of actuator materials under varying conditions. Initially, experimental research was undertaken to analyze the temperature traits of three actuators under ice-free conditions. Three power densities were chosen for the experiment: 0.170 W/cm2, 0.727 W/cm2, and 1.427 W/cm2. The research findings revealed distinct characteristics: plasma actuators and resistance wire actuators exhibited a strip-like high-temperature region during operation, with well-defined boundaries between the high-temperature and low-temperature zones, whereas ceramic-based semiconductor actuators showcased a uniform high-temperature region. As energy consumption rose, the thermal equilibrium temperatures of all three types tended to converge, with resistance wire actuators operating at 1.427 W/cm2, showing the highest temperature rise rate at that power density. Subsequently, experimental research was carried out on the de-icing performance of three actuators under icing conditions at a specific power density. Following 120 s of de-icing, the ice layer covering the surface of the plasma actuator completely melted, forming a cavity. Conversely, the ice layer on the ceramic-based semiconductor actuator remained partially intact in a strip shape. Ice deposits were still visible on the surface of the resistance wire actuator. This observation highlights the remarkable de-icing speed of the plasma actuator. The propulsive force of plasma generated on the fluid inside the ice layer enhances heat transfer efficiency, thereby accelerating the de-icing process of the plasma actuator at the same power density. The analysis of the de-icing performance of these three novel types of actuators establishes a robust groundwork for exploring more effective aircraft de-icing methods. Furthermore, it furnishes theoretical underpinning for the advancement of composite anti-icing and de-icing strategies.

With shared routes of transmission, HBV and HCV co-infection are estimated to occur more in subjects with HIV. This study aimed to characterize and describe the prevalence of HBV and HCV co-infections in a cohort of newly diagnosed HIV+ subjects living in China. We conducted a cross-sectional study among newly diagnosed HIV+ subjects aged 18–100 who participated in surveys on the national HIV molecular epidemiology in 2015 and 2023. (The epidemiological table survey is located in the national database alongside serologic testing). The chi-square test was used to identify changes in infections between the studying populations in 2015 and 2023, and conditional logistic regression models were fit to identify risk factors for each co-infection. Among the 11,024 newly diagnosed HIV+ subjects who were surveyed (n = 4501 in 2015; n = 6523 in 2023), the prevalence of HBV, HCV, and HBV/HCV in 2023 was lower than that in 2015, respectively. No decrease was observed in HCV co-infection in men who had sex with men (MSM) in North China, Northeast China, and East China. Increasing recognition among those at high risk of heterosexual transmission and those with low educational backgrounds is paramount to the prevention and control of HIV/HBV/HCV infections.

BackgroundEnhanced imaging techniques have the overwhelming advantages of being noninvasive and sensitive enough to evaluate the microcirculation of lesions, thus making them accurate in the diagnosis of hepatic lesions. Unfortunately, there is very little research on and knowledge of the imaging features of a rare cancerous condition: hepatic angiosarcoma (HA).Case summaryIn this study, we retrospectively collected the data of six patients who underwent both contrast-enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CECT), and subsequently obtained a definitive histopathologic diagnosis of HA. We described the imaging appearances of HA by comparing CEUS and CECT images. Furthermore, we analyzed these imaging characteristics from the perspective of histopathology and tumorigenesis. The study included the largest number (six) of histopathologically confirmed HA patients who had received CEUS examinations to date.ConclusionBy offering readers comprehensive knowledge of contrast imaging, especially CEUS, in the diagnosis of HA, our study may reduce misdiagnosis and further improve treatment options.

Glucagon-like peptide 1 receptor agonist exenatide (exendin-4) has potential protective capabilities against diabetic kidney disease (DKD). However, the underlying mechanism has not been fully elucidated. The expression of thioredoxin-interacting protein (Txnip) is upregulated during DKD progression by histone acetylation. Sirtuin 1 (SIRT1) is a deacetylase and is decreased in DKD, which indicates that it may regulate Txnip in this disease. Here, we used whole-body heterozygous Sirt1 knockout (Sirt1+/-) and kidney-specific Sirt1 knockout (KSK) mice to investigate whether SIRT1 regulates Txnip via histone deacetylation in DKD and exenatide-alleviated DKD. Exenatide substantially improved renal pathological damage, decreased the albumin-to-creatinine ratio (ACR), upregulated SIRT1 expression, and downregulated Txnip expression in kidneys of high-fat diet-treated C57BL/6J mice. However, these effects diminished in Sirt1+/- and KSK mice under exenatide treatment. The downregulation of Txnip expression by exendin-4 in high-glucose-treated SV40 MES13 cells was hampered during Sirt1 knockdown. These results demonstrate that kidney SIRT1 is indispensable in exenatide-improved DKD and downregulation of Txnip expression. Exendin-4 mechanistically downregulated Txnip histone 3 lysine 9 acetylation (H3K9ac) in a SIRT1-dependent manner and decreased spliced X-box binding protein 1 (XBP1s) recruitment to the Txnip promoter. These findings provide epigenetic evidence elucidating the specific mechanism for exenatide-mediated DKD alleviation and highlight the importance of Txnip as a promising therapeutic target for DKD.

Wang, Liang, Huang et al. evaluate associations between mitochondrial DNA copy number (mtDNA-CN) and HbA1c and weight loss in patients with type 2 diabetes treated with metformin or acarbose, as part of the MARCH study. They find that patients with higher mtDNA-CN lost more weight on metformin, but did not see the same with acarbose.

Objective: To assess the concordance of tumour grade in specimens obtained from diagnostic cystoscopic biopsy and transurethral resection of bladder tumour (TURBT) and explore the risk factors of upgrading. Methods: The medical records of 205 outpatients who underwent diagnostic cystoscopic biopsy before initial TURBT were retrospectively reviewed. Comparative analysis of the tumour grade of biopsy and operation specimens was performed. Tumour grade changing from low-grade to high-grade with or without variant histology was defined as upgrading. Logistic regression analyses were performed to identify the risk factors of upgrading. Results: For the 205 patients, the concordance of tumour grade between specimens obtained from biopsy and operation was 0.639. The concordance for patients who were preoperatively diagnosed with low-grade and high-grade was 0.504 and 0.912, respectively. Univariate and multivariate logistic regression analyses showed that older age, tumour multifocality, high neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and low lymphocyte-to-monocyte ratio (LMR) were significantly associated with upgrading (odds ratio ranging from 0.412 to 4.364). The area under the curve of the different multivariate models was improved from 0.752 to 0.821, and decision curve analysis demonstrated a high net benefit when NLR, LMR, and PLR were added. Conclusion: Diagnostic cystoscopic biopsy may not accurately represent the true grade of primary bladder cancer, especially for outpatients with low-grade bladder cancer. Moreover, older age, tumour multifocality, high NLR, PLR, and low LMR are risk factors of upgrading, and systemic inflammatory markers improve the predictive ability.

Discus fish, Symphysodon spp., have a unique parental care strategy where the fry feed on their parents’ skin mucus after hatching. Here, lipidomics was employed to compare the skin mucus lipid profiles of male or female discus fish during parental and non-parental care. By multivariate statistical analysis, clear separations were found between parental and non-parental female and between parental and non-parental male discus. In the comparison between female discus in the parental and non-parental stages, a total of 107 differentially expressed lipids (DELs) were observed, of which 23 showed increased levels during parental care. For male discus, a total of 108 DELs were found, of which 46 displayed increased levels during parental care. The main DELs were phosphatidyl ethanolamine and phosphatidylinositol, mainly involved in arachidonic acid and sphingolipid metabolism pathways. Further, by comparing parental male and female discus, we found 47 DELs involved in the glycerophospholipid metabolism pathway. Diglyceride showed a higher concentration in the skin mucus of parental females, while phospholipids showed a higher level in that of parental males. Our results revealed changes in the skin mucus lipid profiles of discus fish during parental care, as well as sex-dependent differences between parental fish.

The double-wedge configuration is a typical characteristic shape of the rudder surface of high-speed aircraft. The impact of the shock wave/boundary layer interaction and the shock wave/shock wave interaction resulting from the double wedge on aircraft aerodynamics cannot be ignored. The aerodynamic performance of the aircraft would be seriously affected. Accordingly, to reduce the wave drag, and to relieve the thermal load and pressure load, flow control is required for the shock wave/shock wave interaction and the shock wave/boundary layer interaction induced by the double-wedge configuration. In this paper, double-wedge shock wave/shock wave interaction is controlled by a high-energy surface arc discharge array and observed by high-speed schlieren flow field measurement at Mach 8. The 30-channel discharge array is set on the primary wedge plane, and actuation is generated. Hypersonic V shock wave/shock wave interaction is effectively controlled by the shock wave array induced by the high-energy surface arc discharge array, which makes the shock wave/shock wave interaction structure disappear or intermittent. The potential control mechanism is to reduce strong shock wave interaction by transforming the type of shock wave interaction. Therefore, the ability of plasma array actuation to control complex shock wave/shock wave interaction is verified, which provides a new method for hypersonic shock wave/shock wave interaction control.

Enkianthus calophyllus was once treated as a synonym of E. serrulatus. However, field observations indicate that E. calophyllus is distinct from E. serrulatus but resembles E. perulatus in flowers, leaves, fruits and seeds. Hence, a taxonomic revision of these species was conducted based on morphological comparisons of flowers, leaves, fruits and seeds, as well as molecular analyses of nuclear ribosomal internal transcribed spacer (nrITS) and six plastid DNA markers (psbA-trnH, rpl32-trnL, trnL-trnF, rps16-trnQ, psbJ-petA and matK). The morphological and molecular results reject the synonymization of E. calophyllus with E. serrulatus, and instead show it to be placed in a clade with E. perulatus. Based on molecular evidence and a reassessment of the morphology we synonymize E. calophyllus with the older name E. perulatus.

Background: Personal protective equipment (PPE)-related occupational dermatosis (PROD) represents a significant occupational burden to health care workers (HCWs), and understanding its epidemiology is imperative in formulating mitigation strategies. Objectives: To determine the prevalence of PROD in HCWs, characterize its manifestations, identify its risk factors, and evaluate behavioral modifications of HCW. Methods: A cross-sectional study using an online questionnaire was conducted from July to September 2020. HCWs who had direct contact with COVID-19 patients for a minimum of 2 weeks cumulatively were invited to participate. Results: The prevalence of PROD among 416 valid respondents was 73.8% (307/416), with face masks being the most common cause (93.8% [n = 288]). The most common PROD associated with face masks, protective eyewear, hairnets, gowns, and gloves were acne (71.5% [206/288]), pressure-related injuries (70.7% [99/140]), scalp itch (53.3% [16/30]), itch/rash (78.8% [26/33]), and xerosis (75.0% [27/36]), respectively. Exposure to PPE beyond an hour increased the odds of PROD by 4.8-fold. The majority of HCWs made behavioral modifications to mitigate PROD. Conclusions: We underscore evidence-based recommendations for HCWs to be (1) scheduled hourly breaks from PPE wear, (2) fitted to various PPE models, (3) screened for preexisting dermatoses before deployment, and (4) educated on mitigation strategies and avenues for help should they encounter PROD.

Background: Intraoperative hypotension (IOH) is a common side effect of non-cardiac surgery that might induce poor postoperative outcomes. The relationship between the IOH and severe postoperative complications is still unclear. Thus, we summarized the existing literature to evaluate whether IOH contributes to developing severe postoperative complications during non-cardiac surgery. Methods: We conducted a comprehensive search of PubMed, Embase, Cochrane Library, Web of Science, and the CBM from inception to 15 September 2022. The primary outcomes were 30-day mortality, acute kidney injury (AKI), major adverse cardiac events (myocardial injury or myocardial infarction), postoperative cognitive dysfunction (POCD), and postoperative delirium (POD). Secondary outcomes included surgical-site infection (SSI), stroke, and 1-year mortality. Results: 72 studies (3 randomized; 69 non-randomized) were included in this study. Low-quality evidence showed IOH resulted in an increased risk of 30-day mortality (OR, 1.85; 95% CI, 1.30–2.64; P

Summary: Protein post-translational modifications (PTMs) participate in important bioactive regulatory processes and therefore can help elucidate the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Here, we investigate the involvement of PTMs in ketogenic diet (KD)-improved fatty liver by multi-omics and reveal a core target of lysine malonylation, acetyl-coenzyme A (CoA) carboxylase 1 (ACC1). ACC1 protein levels and Lys1523 malonylation are significantly decreased by KD. A malonylation-mimic mutant of ACC1 increases its enzyme activity and stability to promote hepatic steatosis, whereas the malonylation-null mutant upregulates the ubiquitination degradation of ACC1. A customized Lys1523ACC1 malonylation antibody confirms the increased malonylation of ACC1 in the NAFLD samples. Overall, the lysine malonylation of ACC1 is attenuated by KD in NAFLD and plays an important role in promoting hepatic steatosis. Malonylation is critical for ACC1 activity and stability, highlighting the anti-malonylation effect of ACC1 as a potential strategy for treating NAFLD.

Compression corner shock wave/boundary layer interaction (SWBLI) is a typical shock wave/boundary layer interaction (SWBLI) problem in supersonic/hypersonic flows. In previous studies, the separation flow is usually caused by a single shock wave. However, in the actual aircraft surface configuration, two-stage compression or even multistage compression will produce more complex SWBLI problems. The multi-channel shock structure makes the flow field structure more complicated and also puts forward higher requirements for the flow control scheme. In order to explore a flow control method for the double compression corner shock wave/boundary layer interaction problem, an experimental study is carried out to control the double compression corner shock wave/boundary layer interaction with a high-energy flow pulsed arc discharge array under the condition that the incoming flow velocity Ma 6.0 has both noise flow fields and quiet flow fields. The results show that when UDC = 0.5 kV actuation is applied, the influence range of the hot gas mass flow direction is about 65 mm, which can weaken the shock wave intensity to a certain extent. When UDC = 1 kV actuation is applied, the influence range of the hot gas mass flow direction extends to 85 mm, and the actuation has a significant control effect on the flow field. Through spatio-temporal evolution analysis and spatial gradient threshold processing of high-speed schlieren images of actuated flow fields, the feasibility of controlling the hypersonic double compression corner shock wave/boundary layer interaction by using a high-energy flow pulsed arc discharge array is verified. The control law of a high-energy flow pulsed arc discharge array acting on the double compression corner shock wave/boundary layer interaction is revealed.

Abstract Prostate cancer (PCa) growth and progression are uniquely dependent on androgens, making the androgen receptor pathway a prime target for therapy; however, cancer progression to androgen independence leads to treatment failure and poor prognosis. In recent years, alternative therapeutic pathways for PCa have been extensively explored, such as the PTEN/PI3K/AKT pathway, cell cycle, and DNA repair. In the present study, we discovered that RASAL2, a RAS-GTPase-activating protein, acted as an oncogene to regulate cancer cell proliferation and the cell cycle and contributed to tumorigenesis via the PI3K/AKT/cyclin D1 pathway. First, RASAL2 expression was higher in PCa tumour and metastatic lymph node tissues than in matched adjacent nontumor tissues and was associated with higher PCa tumour stage, Gleason score and poorer prognosis. Mechanistically, we found that RASAL2 promoted tumour cell proliferation, the transition from G1 to S phase in vitro and tumour growth in vivo. Furthermore, we demonstrated that RASAL2 facilitated phosphorylation of AKT, which in turn increased the expression of cyclin D1 encoded by the CCND1 gene. In addition, there was a positive correlation between the expression of RASAL2 and cyclin D1 in subcutaneous xenografts and clinical specimens. Taken together, these findings indicate that RASAL2 plays an oncogenic role in prostate cancer and may promote PCa tumorigenesis through PI3K/AKT signalling and cyclin D1 expression.

Abstract Background Patatin-like phospholipase domain containing 3 (PNPLA3) is the main nonalcoholic fatty liver disease (NAFLD) susceptibility. Its expression is regulated tightly by nutritional and energy status, but the mechanism of epigenetic regulation of PNPLA3 gene by nutritional dietary factors has not been reported. Here, we investigated the effect and mechanism of Sirtuin 1 (SIRT1) regulated H3K9 deacetylation on PNPLA3 transcriptional expression in vivo and in vitro. Methods Mouse models of fasting/re-feeding transition and nonalcoholic fatty liver induced by high Sucrose diet were constructed; and HepG2 cells were treated with serum- and glucose-free medium or exposed to high glucose and high insulin, to generate fasting and high-glucose-induced lipid deposition cell states. Enrichment levels of histone H3K9 acetylation and sterol responsive element binding protein-1c (SREBP-1c) at the PNPLA3 promoter were observed by ChIP-qPCR. PNPLA3 gene expression was detected by real-time PCR; SIRT1 protein expression was detected by western blot. And lipid deposition was detected by Oil Red O. Results H3K9ac levels at SRE regions of PNPLA3 promoter were found to be decreased in mice during fasting and increase during refeeding, and increased in mice with NAFLD induced by high-sucrose diet. The change pattern of PNPLA3 promoter H3K9Ac physiologically (fasting/refeeding) and pathologically was consistent with that of PNPLA3 gene expression, but opposite to that of SIRT1 protein expression. In HepG2 cells, overexpression of SIRT1 inhibited high-glucose induced hyper-acetylation of H3K9 at PNPLA3 promoter, and silent expression of SIRT1 suppressed fasting-induced hypo-acetylation of H3K9. Overexpression of SIRT1 prevented basal and SREBP-1c-driven PNPLA3 gene expression and also prevented the endogenous binding of SREBP-1c to PNPLA3. Conclusions We first preliminarily revealed SIRT1 may regulate PNPLA3 gene expression by affecting SREBP-1-driven transcription via acetylation modification of H3K9.

Abstract Hypersonic boundary layer transition is a hot yet challenging problem restricting the development and breakthrough of hypersonic aerodynamics. In recent years, despite great progress made by wind tunnel experiment, transition mechanism and transition prediction, only partial knowledge has been gained so far. In this paper, firstly, the specific scenarios of hypersonic boundary layer transition control are clarified. Secondly, the experimental research progress and mechanism of passive control and active control methods under different hypersonic transition control demands are summarized, with their advantages and disadvantages being analyzed separately. Plasma actuation is easy to produce controllable broadband aerodynamic actuation, which has potential in the field of boundary layer transition control. Hence, the following part of the paper focuses on plasma flow control. The feasibility of plasma actuation to control the hypersonic boundary layer transition is demonstrated and the research ideas are presented. Finally, hypersonic boundary layer transition control methods are summarized and the direction of future research is prospected.

BackgroundRecent studies have shown that red blood cell distribution width (RDW) has emerged as a novel predictor of cardiovascular diseases. We aim to investigate the association between RDW and the risk of coronary artery lesions (CALs) in pediatric patients with Kawasaki disease (KD).MethodsKD patients were classified as the CALs group (patients with CALs) and non-CALs group (patients without CALs). Differences among the groups were analyzed by Mann-Whitney U-test and Chi-square analysis. The independent risk factors of CALs were identified by multivariate logistic regression analysis, followed by receiver operating characteristic (ROC) curve analysis to calculate the optimal cut-off value.ResultsThe red blood cell distribution width (RDW) and C-reactive protein were significantly higher in the CALs group than those in the non-CALs group (p 13.86%, with a sensitivity of 75.79% and specificity of 92.81% (AUC = 0.869, 95% CI = 0.844–0.892; p 13.86%) may be used as novel biomarkers for early predicting CALs in KD patients during the acute phase.

Background. Patatin-like phospholipase domain-containing 3 (PNPLA3) is a major susceptibility gene for nonalcoholic fatty liver disease (NAFLD), and its rs738409 (I148M) polymorphism is associated with the occurrence and progression of NAFLD. Endoplasmic reticulum (ER) stress-related hepatocyte lipoapoptosis contributes to the progress of NAFLD. PNPLA3 is also known as a member of the calcium-independent phospholipase A2ε family, which can hydrolyze fatty acids to generate lysophosphatidylcholine (LPC) that induces ER stress-related hepatocyte lipoapoptosis. Whether the PNPLA3 risk genotype 148M/M is involved in more severe ER stress-associated lipoapoptosis is unclear. Methods. A PNPLA3148I knock-in HepG2 cell model was constructed based on HepG2 expressing PNPLA3 148M/M using the Cas9/sgRNA system. PNPLA3 148M/M, I/M, and I/I cells were treated with 0.3 mM palmitic acid (PA) for 24 h to induce lipid deposition. Cellular lipid deposition was detected by oil red staining. Apoptosis was observed by TUNEL. LPC was determined by ELISA, and the expression of PNPLA3, the ER stress marker Bip, molecules involved in the ER stress PERK/elF-2a pathway, and its downstream C/EBP homologous protein (CHOP)-mediated apoptotic pathway were detected by western blot. Results. The results showed no difference in PNPLA3 basal expression and basal hepatocyte lipid content between the three genotypes of cells. Lipid deposition and apoptosis were more severe in PNPLA3 148M/M and 148I/M cells than in I/I cells after PA treatment. PA-induced upregulation of protein expression of Bip, ER stress-responsive PERK pathway molecules p-PERK, p-eIF2α, CHOP, and CHOP-associated apoptotic molecules PUMA and Bax were more pronounced in PNPLA3 148M/M cells than in PNPLA3 148I/I cells. The basal LPC levels and the PA-treated increase of LPC levels in the cell culture supernatants did not differ between the three genotypic cells. Conclusion. PNPLA3 148M/M cells were more susceptible to PA-induced lipid deposition and ER stress-related apoptosis than 148I/I cells, and the proapoptotic susceptibility of PNPLA3 148M/M is independent of LPC.

To test variance homogeneity, various likelihood-ratio based tests such as the Bartlett's test have been proposed. The null distributions of these tests were generally derived asymptotically or approximately. We re-examine the restrictive maximum likelihood ratio (RELR) statistic, and suggest a Monte Carlo algorithm to compute its exact null distribution, and so its p-value. It is much easier to implement than most existing methods. Simulation studies indicate that the proposed procedure is also superior to its competitors in terms of type I error and powers. We analyse an environmental dataset for an illustration.

Abstract Background The broad continuum between tropical and temperate floras in Eastern Asia (EAS) are thought to be one of the main factors responsible for a prominent species diversity anomaly of temperate plants between EAS and eastern North America (ENS). However, how the broad continuum and niche evolution between tropical and temperate floras in EAS contributes to lineage divergence and species diversity remains largely unknown. Results Population genetic structure, demography, and determinants of genetic structure [i.e., isolation-by-distance (IBD), isolation-by-resistance (IBR), and isolation-by-environment (IBE)] of Machilus thunbergii Sieb. et Zucc. (Lauraceae) were evaluated by examining sequence variation of ten low-copy nuclear genes across 43 populations in southeast China. Climatic niche difference and potential distributions across four periods (Current, mid-Holocene, the last glacial maximum, the last interglacial) of two genetic clusters were determined by niche modelling. North and south clusters of populations in M. thunbergii were revealed and their demarcation line corresponds well with the northern boundary of tropical zone in China of Zhu & Wan. The divergence time between the clusters and demographic expansion of M. thunbergii occurred after the mid-Pleistocene climate transition (MPT, 0.8–1.2 Ma). Migration rates between clusters were asymmetrical, being much greater from north to south than the reverse. Significant effects of IBE, but non-significant effects of IBD and IBR on population genetic divergence were detected. The two clusters have different ecological niches and require different temperature regimes. Conclusions The north-south genetic differentiation may be common across the temperate-tropical boundary in southeast China. Divergent selection under different temperature regimes (possibly above and below freezing temperature in winter) could account for this divergence pattern. The broad continuum between tropical and temperate floras in EAS may have provided ample opportunities for tropical plant lineages to acquire freezing tolerance and to colonize the temperate regions during the late-Cenozoic global cooling. Our findings shed deeper insights into the high temperate plant species diversity in EAS.

Background Both type 1 diabetes mellitus (T1DM) and metabolic syndrome (MetS) are associated with an elevated risk of morbidity and mortality yet with increasing heterogeneity. This study primarily aimed to evaluate the prevalence of MetS among adult patients with T1DM in China and investigate its associated risk factors, and relationship with microvascular complications. Methods We included adult patients who had been enrolled in the Guangdong T1DM Translational Medicine Study conducted from June 2010 to June 2015. MetS was defined according to the updated National Cholesterol Education Program criterion. Logistic regression models were used to estimate the odds ratio (OR) for the association between MetS and the risk of diabetic kidney disease (DKD) and diabetic retinopathy (DR). Results Among the 569 eligible patients enrolled, the prevalence of MetS was 15.1%. While female gender, longer diabetes duration, higher body mass index, and glycosylated hemoglobin A1c (HbA1c) were risk factors associated with MetS (OR, 2.86, 1.04, 1.14, and 1.23, respectively), received nutrition therapy education was a protective factor (OR, 0.46). After adjustment for gender, age, diabetes duration, HbA1c, socioeconomic and lifestyle variables, MetS status was associated with an increased risk of DKD and DR (OR, 2.14 and 3.72, respectively; both P

ABSTRACT As the fourth most common gynecological cancer, cervical cancer has resulted in more than 300,000 deaths worldwide in 2020. The expression of the human papillomavirus (HPV) oncogenes E6 and E7 is significantly involved in the initiation and progression of cervical neoplasia. Additionally, the composition of the vaginal microbiome was also closely associated with the ability of HPV to induce cervical cancer. However, the relationship between the expression of HPV E6/E7 oncogene and the composition of the vaginal microbiome has not been clearly explored. In our present study, to investigate the relationship between the HPV E6/E7 oncogene and vaginal microbiome, cervical swabs from 115 patients were collected, and their vaginal microbiomes were analyzed by using metagenomics sequencing. Along with the progression of cervical lesions, the diversity of cervical flora increased gradually, and the abundance of Lactobacillus decreased. Compared with the HPV group, the prevalence of HPV E6/E7 and oncogene expression level were significantly upregulated in cervical intraepithelial neoplasia (CIN) and cervical cancer (CC) groups. Additionally, a positive correlation between the expression of the HPV oncogene and the genera Sneathia, Salmonella, Leptotrichia, Pseudomonas, and Roseovarius in the HPV group was observed. In the CIN group, the enrichment of the genera Sneathia and Megasphaera was weakly linked with HPV oncogene overexpression. In the CC group, a strong association between the overabundance of the genera Peptostreptococcus and Enterococcus and the high expression of HPV oncogene was also found. The increased diversity of the vaginal microbiota and the decreased Lactobacillus abundance were significantly associated with the severity of cervical disease, and the expression of the HPV oncogene could also be regulated by certain pathogens in different stages of cervical lesions. IMPORTANCE The main findings of this study were that we clarified the associations of the different bacterial species with the expression of human papillomavirus (HPV) oncogenes at different stages of cervical cancer. Along with the severity of cervical lesions, the abundance of the genus and species of Lactobacillus obviously declined, while the aerobic and anaerobic bacteria, as well as the prevalence and expression of HPV E6/E7 oncogene, were increased dramatically.

The thread measurement methods based on machine vision are easily disturbed by the environment(e.g. dust,iron filings, oil stains, etc.), resulting in inaccurate measurement results. This paper improves the R2 Unet model by adding the Attention mechanism, and proposes an external thread measurement method based on AA R2 Unet and hidden Markov model(HMM). Firstly, to overcome the interference of dust, iron filings et al, the AA R2 Unet model was designed to identify and extract the external threads. Secondly, the feature information on gradient direction of thread edge points is calculated, HMM was used to classify the thread edge points so that the threaded parts can be placed at any angle during the measurement. Finally, the method with the gathered dataset was evaluated. The results show that the segmentation accuracy of the thread edge extraction method based on AA R2 Unet is 95.92%, the classification accuracy of thread edge points based on HMM is above 86% and the comprehensive measurement error is within 0.01 mm.

Renal fibrosis commonly occurs in the process of chronic kidney diseases. Here, we explored the role of Jumonji domain containing 3 (Jmjd3)/interferon regulatory factor 4 (IRF4) axis in activation of myeloid fibroblasts and transition of M2 macrophages into myofibroblasts transition (M2MMT) in kidney fibrosis. In mice, Jmjd3 and IRF4 were highly induced in interstitial cells of kidneys with folic acid or obstructive injury. Jmjd3 deletion in myeloid cells or Jmjd3 inhibitor reduced the levels of IRF4 in injured kidneys. Myeloid Jmjd3 depletion impaired bone marrow-derived fibroblasts activation and M2MMT in folic acid or obstructive nephropathy, resulting in reduction of extracellular matrix (ECM) proteins expression, myofibroblasts formation and renal fibrosis progression. Pharmacological inhibition of Jmjd3 also prevented myeloid fibroblasts activation, M2MMT, and kidney fibrosis development in folic acid nephropathy. Furthermore, IRF4 disruption inhibited myeloid myofibroblasts accumulation, M2MMT, ECM proteins accumulation, and showed milder fibrotic response in obstructed kidneys. Bone marrow transplantation experiment showed that wild-type mice received IRF4-/- bone marrow cells presented less myeloid fibroblasts activation in injured kidneys and exhibited much less kidney fibrosis after unilateral ureteral obstruction. Myeloid Jmjd3 deletion or Jmjd3 inhibitor attenuated expressions of IRF4, α-smooth muscle actin and fibronectin and impeded M2MMT in cultured monocytes exposed to IL-4. Conversely, overexpression IRF4 abrogated the effect of myeloid Jmjd3 deletion on M2MMT. Thus, Jmjd3/IRF4 signaling has a crucial role in myeloid fibroblasts activation, M2 macrophages to myofibroblasts transition, extracellular matrix protein deposition, and kidney fibrosis progression.

Endoplasmic reticulum (ER) is the principal organelle for protein synthesis, such as hepatokines and transmembrane proteins, and is critical for maintaining physiological function. Dysfunction of ER is associated with metabolic disorders. However, the role of ER homeostasis as well as hepatokines in the progression of non-alcoholic fatty liver disease (NAFLD) remains to be elucidated. Here we comprehensively analyzed the RNA-seq profiles of liver biopsies from 206 NAFLD patients and 10 controls from dataset GSE135251. The co-expression modules were constructed based on weighted gene co-expression network analysis and six co-expression modules were identified, of which brown module stood out to be significantly associated with fibrosis stage and NAFLD activity score (NAS). Subsequently, cytoscape with cytoHubba plugin was applied to identify hub genes in the brown module. GO and KEGG enrichment analysis of the top 20 hub genes were performed and showed the involvement of extracellular matrix formation, collagen synthesis and decomposition, etc. Further, the expression of the top 20 hub genes were found to be a consistent increasing trend as the fibrosis stages and NAS increased, which have been validated both in HFD fed and HFHC fed mice. Among these genes, THY1, PTGDS, TMPRSS3, SPON1, COL1A2, RHBDF1, COL3A1, COL5A1, COL1A1 and IGFBP7 performed well in distinguishing fibrosis stage, while COL1A2, COL3A1, THY1, RHBDF1 and COL1A2 exhibited good capacity to discriminate NAS. Besides, RHBDF1, COL3A1, QSOX1, STING1, COL5A1, IGFBP7, COL4A2, COL1A1, FKBP10 and COL1A2 also showed a strong power in the diagnosis of NAFLD. In addition, COL1A1, COL1A2, COL3A1, COL8A2, IGFBP7, PGF, PTGDS, SPON1, THY1 and TIMP1 were identified as secretome genes from the top 20 hub genes. Of them, circulated THY1 and collagen III level were validated to be significantly elevated in the MCD diet-induced mice. Thus, we provided a systemic view on understanding the pathological roles and mechanisms of ER as well as secretome in NAFLD progression. THY1, COL1A1, COL1A2, COL3A1 and RHBDF1 could be served as candidate biomarkers to evaluate the progression of NAFLD.

Renal fibrosis is an important pathological biomarker of chronic kidney disease (CKD). Stimulator of interferon genes/TANK binding kinase 1 (STING/TBK1) axis has been identified as the main regulator of innate immune response and closely related to fibrotic disorder. However, the role of STING/TBK1 signaling pathway in kidney fibrosis is still unknown. In this study, we investigated the effect of pharmacological inhibition of STING/TBK1 signaling on renal fibrosis induced by folic acid (FA). In mice, TBK1 was significantly activated in interstitial cells of FA-injured kidneys, which was markedly inhibited by H-151 (a STING inhibitor) treatment. Specifically, pharmacological inhibition of STING impaired bone marrow-derived fibroblasts activation and macrophage to myofibroblast transition in folic acid nephropathy, leading to reduction of extracellular matrix proteins expression, myofibroblasts formation and development of renal fibrosis. Furthermore, pharmacological inhibition of TBK1 by GSK8612 reduced myeloid myofibroblasts accumulation and impeded macrophage to myofibroblast differentiation, resulting in less deposition of extracellular matrix protein and less severe fibrotic lesion in FA-injured kidneys. In cultured mouse bone marrow-derived monocytes, TGF-β1 activated STING/TBK1 signaling. This was abolished by STING or TBK1 inhibitor administration. In addition, GSK8612 treatment decreased levels of α-smooth muscle actin and extracellular matrix proteins and prevents bone marrow-derived macrophages to myofibroblasts transition in vitro. Collectively, our results revealed that STING/TBK1 signaling has a critical role in bone marrow-derived fibroblast activation, macrophages to myofibroblasts transition, and kidney fibrosis progression.

Crosswinds will lead to large-scale flow separation in the nacelle inlets, which seriously affects the flight safety of the aircraft; there is an urgent need to develop flow control measures. As a plasma flow control method, the application of surface dielectric barrier discharge in the field of nacelle inlet separation control is of great significance for improving the intake quality. Based on the characteristic law of the baseline flow field, the flow control effect of the nacelle inlet separation flow field experiments with NS-DBD, and the influence of the actuation frequency on the flow control is discussed. A comparative experimental study of NS-DBD and AC-DBD is carried out. Finally, the flow control mechanisms for both are discussed. The results show that under the condition that the flow velocity of the wind tunnel is 35 m/s and the crosswind angle is 10°, the average total pressure loss coefficient and distortion index decrease by 29.62% and 44.14% by NS-DBD actuation. At the same time, exists an inherent optimal coupling frequency in NS-DBD, and the control effect of NS-DBD is better than that of AC-DBD. NS-DBD mainly through shock waves and induced vortices, while AC-DBD mainly through the induced generation of near-wall jets to reduce the inverse pressure gradient and improve nacelle flow separation.

Abstract Hypoxia inducible factor-1α (HIF-1α) up-regulates the expression of programmed death ligand-1 (PD-L1) in some extracranial malignancies. However, whether it could increase PD-L1 expression in intracranial tumor is still unknown. Here, we explored the relationship between HIF-1α and PD-L1 expression in glioma, and investigated their clinical significance. In glioma patients, HIF-1α and PD-L1 were overexpressed in high grade glioma tissues and were significantly associated with poor survival. In glioma cells, PD-L1 expression was induced under hypoxia condition, and the enhanced PD-L1 expression was abrogated by either HIF-1α knock-down or HIF-1α inhibitor treatment. Furthermore, ChIP-qPCR analysis showed the direct binding of HIF-1α to PD-L1 proximal promoter region, providing evidence that HIF-1α up-regulates PD-L1 in glioma. In glioma murine model, the combination treatment with HIF-1α inhibitor and anti-PD-L1 antibody caused a more pronounced suppressive effect on tumor growth compared to either monotherapy. Immunologically, the combination treatment improved both dendritic cell (DC) and CD8+ T cell activation. Overall, our results demonstrated that positive correlation between PD-L1 and HIF-1α in glioma, and provide an alternative strategy, inhibiting HIF-1α, as combination therapies with immunotherapies to advance glioma treatment.

Abstract Aims/Introduction Given that mutations related to maturity‐onset diabetes of the young (MODY) are rarely found in Chinese populations, we aim to characterize the mutation spectrum of MODY pedigrees. Materials and Methods Maturity‐onset diabetes of the young candidate gene‐ or exome‐targeted capture sequencing was carried out in 76 probands from unrelated families fulfilling the clinical diagnostic criteria for MODY. MAF

Prostate lymphoma (PL) is rarely observed and may be concurrently presented with prostate adenocarcinoma. Moreover, the appearance of PL on conventional imaging is similar with prostate adenocarcinoma. Thus, most of PL is diagnosed through prostate biopsy, or accidentally found in the specimens of surgery. Prostate-specific membrane antigen (PSMA) PET/CT has improved the management of prostate adenocarcinoma. While, the question regarding whether it benefits the discovery of the characteristics of PL is unknown. A 32-year-old man presented with worsening dysuria for 1 month, and the prostate-specific antigen (PSA) concentration was normal. While the pelvic MRI showed a mass in the prostate and multiple enlarged lymph nodes in the bilateral inguinal area. Then, the diagnosis of prostate adenocarcinoma was considered, but the serum PSA was normal and he was younger than most patients. So, 18F-PSMA PET/CT was then performed to further reveal the characteristics of the lesion and guide biopsy. However, there was no abnormal PSMA uptake in the lesion of the prostate and lymph nodes of the pelvic cavity and bilateral inguinal area. These lesions presented with increased glucose metabolism on fluorodeoxyglucose (FDG) PET/CT, and the prostate biopsy was then performed. PL was confirmed based on the results of the histopathologic examination, and the patient subsequently received systemic chemotherapy plus radiotherapy. Fortunately, the symptoms and the lesions completely disappeared after radiotherapy. The clinical symptoms of PL are atypical, and PL and adenocarcinoma may be concurrently presented. Moreover, distinguishing PL from prostate adenocarcinoma based on the appearance of conventional imaging is difficult. As opposed to prostate adenocarcinoma, a high FDG-avidity and low PSMA uptake by lymphoma either in the prostate or metastases are seen. So, PSMA PET/CT combined with FDG PET/CT can non-invasively identify the characteristics and origin of PL.

Underdeveloped reading comprehension skills can limit academic success; a particular challenge for English language learners (ELLs). The current study investigated whether a web-based text structure strategy, delivered via the Intelligent Tutoring of Structure Strategy (ITSS) program to adult Chinese ELLs, improved students' use of reading strategies and/or overall reading comprehension. Using a quasi-experimental nonequivalent control group design, 207 adult Chinese ELLs from four classes were assigned to intervention or control groups. The intervention group utilized the ITSS to support their English reading instruction, whereas the control group was exposed to only traditional instruction. Our results indicate that the ITSS intervention had a statistically significant positive effect on adult Chinese ELLs' reading comprehension ([beta] = 3.07, p < 0.001) with Cohen's d = 0.43, as measured by the College English Test--4 (CET-4). Furthermore, we found that Chinese ELLs reported using more higher-order reading strategies (p < 0.01) after the intervention and there was no significant change of reported reading strategy usage for the control group from pretest and post-test. However, the current study did not provide evidence that the change in use of reading strategies mediated the relationship between the intervention/control condition and Chinese ELLs' reading comprehension.

Introduction Advancing renal fibrosis is the common histopathological feature of chronic obstructive nephropathy, representing the final pathway of nearly all chronic and progressive nephropathies. Increasing evidences suggest that circular RNAs (circRNAs) are crucial regulatory molecules present at virtually every level of the cellular pathophysiological process. Nonetheless, there are a few evidences for the role of circRNAs in renal fibrosis induced by obstructive nephropathy. Aims We performed RNA-seq analysis to analyze the expression profiles of circRNAs in the obstructed kidneys to identify the potential circRNAs and their network. Methods With silk ligated the left ureter to establish a mice unilateral ureteral obstruction (UUO) model. Renal tissue circRNAs were obtained and were screened by a circRNA microarray. The circRNA-miRNA-mRNA regulatory network and the target genes were visualized using Cytoscape software. Results The microarray results showed that 5454 and 2935 circRNAs were detected in the control and UUO group, respectively. There were 605 circRNAs up-regulated and 745 circRNAs down-regulated in the obstructive kidneys. The top 5 up-regulated and down-regulated circRNAs were chosen for predicting the circRNA/miRNA/target mRNAs triple network. The GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis showed that these circRNAs and the triple network were enriched in the process of apoptosis, p53 signaling pathway, cell growth and cell death, which might participate in the pathogenesis of obstructive nephrology. Conclusion Our results show that the dis-regulated circRNAs might play crucial roles in the pathogenesis of obstructive nephropathy, which proceeds to identify novel therapeutic targets for chronic kidney disease.

Background: Obesity is associated with the development and progression of c hronic kidney disease. Emerging evidence suggests that glucagon-like p eptide-1 receptor agonist could reduce renal damage and albuminuria. Sirtuin 1 (S IRT1) was considered as a crucial regulator in metabolism-related kidney disease. He rein, the role of SIRT1 in liraglutide-ameliorated high-fat diet (HFD)-induced kidney injury was illustrated. Methods: Male C57BL/6 mice were fed HFD for 20 weeks to induce kidney injury that was then treated with liraglutide for 8 weeks to estimate its prote ctive effect on the kidney. Also, the mechanism of the drug in SV40 MES 13 (SV40) mouse mes angial cells was elucidated. Results: Liraglutide treatment ameliorated HFD-induced metabolic disorders, including hyperglycemia, increasing body weight, and insulin resistance. In addition, kidney weight, urine albumin-to-creatinine, and kidney morphological changes such as vacuolated tubules, glomerulomegaly, thickened glomerular basement membrane, and tubulointerstitial fibrosis were also significantly ameliorated. Furthermore, apoptotic cells and apoptosis markers were downregulated in the kidney of liraglutide-treated mice. In addition, the expression of SIRT1 protein was upregula ted, whereas thioredoxin-interacting protein (TXNIP), which serves as a mediator of oxid ative stress and apoptosis in metabolism disease, was downregulated by liraglutide. In SV4 0 cells, the effect of liraglutide on reversing the upregulation of cleaved caspase-3 induced by high glucose (30 mM) was hampered when SIRT1 was knocked down; also, the dow nregulation of TXNIP by liraglutide was blocked. Conclusions: Liraglutide might have a beneficial effect on metabolism-relate d kidney damage by inhibiting apoptosis via activation of SIRT1 and supp ression of TXNIP pathway.

Abstract Background The benefit of axillary lymph node dissection (ALND) in breast cancer patients with one or two positive sentinel lymph nodes (SLNs) remains inconclusive. The purpose of this study was to identify risk factors independently associated with axillary lymph node (ALN) metastasis. Methods We retrospectively analyzed data from 389 Chinese breast cancer patients with one or two positive SLNs who underwent ALND. Univariate and multivariate logistic regression analyses were performed to identify ALN metastasis-associated risk factors. Results Among the 389 patients, 174 (44.7%) had ALN metastasis, while 215 (55.3%) showed no evidence of ALN metastasis. Univariate analysis revealed significant differences in age (

With the development of NK cell-directed therapeutic strategies, the actual effect of NK cells on the cellular SIV DNA levels of the virus in SIV-infected macaques in vivo remains unclear. In this study, five chronically SIVmac239-infected, treatment-naïve rhesus macaques were euthanized, and the blood, spleen, pararectal/paracolonic lymph nodes (PaLNs), and axillary lymph nodes (ALNs) were collected. The distributional, phenotypic, and functional profiles of NK cells were detected by flow cytometry. The highest frequency of NK cells was found in PBMC, followed by the spleen, while only 0~0.5% were found in LNs. Peripheral NK cells also exhibited higher cytotoxic potential (CD56− CD16+ NK subsets) and IFN-γ-producing capacity but low PD-1 and Tim-3 levels than those in the spleen and LNs. Our results demonstrated a significant positive correlation between the frequency of NK cells and the ratios of cellular SIV DNA/RNA in HLADR− CD4+ T cells (r = 0.6806, p < 0.001) in SIV-infected macaques, despite no discrepancies in the cellular SIV DNA or RNA levels that were found among the blood, spleen, and LNs. These findings showed a profile of NK cell frequencies and NK cytotoxicity levels in different immune organs from chronically SIVmac239-infected, treatment-naïve rhesus macaques. It was suggested that NK cell frequencies could be closely related to SIV DNA/RNA levels, which could affect the transcriptional activity of SIV proviruses. However, the cytotoxicity effect of NK cells on the latent SIV viral load in LNs could be limited due to the sparse abundance of NK cells in LNs. The development of NK cell-directed treatment approaches aiming for HIV clearance remains challenging.

It has been a long time that the relationship between serum calcium levels and Alzheimer’s disease (AD) remains unclear. Until recently, observational studies have evaluated the association between serum calcium levels and the risk of AD, however, reported inconsistent findings. Meanwhile, a Mendelian randomization (MR) study had been conducted to test the causal association between serum calcium levels and AD risk, however, only selected 6 serum calcium SNPs as the instrumental variables. Hence, these findings should be further verified using additional more genetic variants and large-scale genome-wide association study (GWAS) dataset to increase the statistical power. Here, we conduct an updated MR analysis of the causal association between serum calcium levels and the risk of AD using a two-stage design. In discovery stage, we conducted a MR analysis using 14 SNPs from serum calcium GWAS dataset (N = 61,079), and AD GWAS dataset (N = 63,926, 21,982 cases, 41,944 cognitively normal controls). All four MR methods including IVW, weighted median, MR-Egger, and MR-PRESSO showed a reduced trend of AD risk with the increased serum calcium levels. In the replication stage, we performed a MR analysis using 166 SNPs from serum calcium GWAS dataset (N = 305,349), and AD GWAS dataset (N = 63,926, 21,982 cases, 41,944 cognitively normal controls). Only the weighted median indicated that genetically increased serum calcium level was associated with the reduced risk of AD. Hence, additional studies are required to investigate these findings.

Objectively evaluating different lines of evidence within a formalized framework is the most efficient and theoretically grounded approach for defining robust species hypotheses. Asteropyrum Drumm. et Hutch. is a small genus of perennial herb containing two species, A. cavaleriei and A. peltatum. The distinction of these two species mainly lies in the shape and size of leaf blades. However, these characters have been considered labile and could not differentiate the two species reliably. In this study, we investigated the variation of the leaf blades of 28 populations across the whole range of Asteropyrum using the landmark-based geometric morphometrics (GMM), sought genetic gaps within this genus using DNA barcoding, phylogenetic reconstruction and population genetic methods, and compared the predicted ecological niches of the two species. The results showed that the leaf form (shape and size) was overlapped between the two species; barcode gap was not detected within the genus Asteropyrum; and little ecological and geographical differentiation was found between the two taxa. Two genetic clusters detected by population genetic analysis did not match the two morphospecies. The results suggest that there are no distinct boundaries between the two species of Asteropyrum in terms of morphology, genetics and ecology and this present classification should be abandoned. We anticipate that range-wide population genomic studies would properly delineate the species boundaries and help to understand the evolution and speciation within Asteropyrum.

Metformin is the first-line anti-diabetic drug for type 2 diabetes. It has been found to significantly reduce liver aminotransferase in nonalcoholic fatty liver disease (NAFLD). However, whether metformin improves NAFLD progression remains controversial. Sirtuin 1 (SIRT1), an NAD+-dependent deacetylase, plays a vital role in hepatic steatosis and inflammation. Here, we investigated the effect of metformin on steatohepatitis and the role of SIRT1 in diet-induced obese (DIO) mice. The results showed that metformin significantly reduced body weight and fat mass of DIO mice. In addition, metformin also alleviated adiposity and hepatic steatosis, and greatly upregulated uncoupling protein 1 (UCP1) expression in adipose tissues of DIO mice. Unexpectedly, the effects of metformin on reducing body weight and alleviating hepatic steatosis were not impaired in Sirt1 heterozygous knockout (Sirt1+/−) mice. However, SIRT1-deficiency remarkably impaired the effects of metformin on lowering serum transaminases levels, downregulating the mRNA expression of proinflammatory factors, and increasing the protein level of hepatic Cholesterol 25-Hydroxylase (CH25H), a cholesterol hydroxylase in cholesterol catabolism. In summary, we demonstrated that metformin alleviates steatohepatitis in a SIRT1-dependent manner, and modulation of M1 polarization and cholesterol metabolism may be the underlying mechanism.

The accurate classification of crop pests and diseases is essential for their prevention and control. However, datasets of pest and disease images collected in the field usually exhibit long-tailed distributions with heavy category imbalance, posing great challenges for a deep recognition and classification model. This paper proposes a novel convolutional rebalancing network to classify rice pests and diseases from image datasets collected in the field. To improve the classification performance, the proposed network includes a convolutional rebalancing module, an image augmentation module, and a feature fusion module. In the convolutional rebalancing module, instance-balanced sampling is used to extract features of the images in the rice pest and disease dataset, while reversed sampling is used to improve feature extraction of the categories with fewer images in the dataset. Building on the convolutional rebalancing module, we design an image augmentation module to augment the training data effectively. To further enhance the classification performance, a feature fusion module fuses the image features learned by the convolutional rebalancing module and ensures that the feature extraction of the imbalanced dataset is more comprehensive. Extensive experiments in the large-scale imbalanced dataset of rice pests and diseases (18,391 images), publicly available plant image datasets (Flavia, Swedish Leaf, and UCI Leaf) and pest image datasets (SMALL and IP102) verify the robustness of the proposed network, and the results demonstrate its superior performance over state-of-the-art methods, with an accuracy of 97.58% on rice pest and disease image dataset. We conclude that the proposed network can provide an important tool for the intelligent control of rice pests and diseases in the field.