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Understanding flower developmental processes is a prerequisite for improving flowering 'plants' production. Adonis amurensis is a fascinating spring ephemeral plant that develops its flower organs underground. Nevertheless, knowledge of the molecular mechanisms driving this particular process is scarce. Herein, we examined transcriptional changes during underground flower differentiation in A. amurensis and unveiled key differently regulated genes and pathways. High-throughput RNA sequencing of meristems at different flower developmental stages, including flower primordium (FP), sepal stage (SE), perianth primordium (PE), stamen stage (ST), and pistil stage (PI), identified 303,234 unigenes that showed 44.79% similarity with sequences in Aquilegia coerulea. Correlations, principal component, and differentially expressed genes (DEGs) analyses revealed that few molecular changes occurred during the transition from PE to ST. Many DEGs exhibited stage-specific regulations. Transcription factor (TF) and phytohormone family genes are critical regulators of the floral differentiation process in A. amurensis. The most differentially regulated TFs were MADS, FAR1, MYBs, AP2/ERF, B3, C2H2, and LOBs. We filtered out 186 candidate genes for future functional studies, including 18 flowering/circadian-related, 32 phytohormone-related, and TF family genes. Our findings deepen our understanding of the underground flower differentiation process and offer critical resources to dissect its regulatory network in A. amurensis. These findings establish a foundational platform for researchers dedicated to exploring the unique phenotypic characteristics of this specific flowering modality and delving into the intricate molecular mechanisms underpinning its regulation and expression., (© 2024. The Author(s).)

Background: The population with latent tuberculosis infection (LTBI) represents a potential pool of patients with active tuberculosis (ATB). T-SPOT.TB is an important test tool for screening LTBI. Owing to the large population of LTBI patients in China, it is necessary to identify a high-risk group for LTBI and enlarge tuberculosis preventive treatment (TPT) to reduce the incidence of ATB., Methods: Hospitalized patients with positive T-SPOT.TB results were recruited from January 2013 to December 2016. Patients with ATB were excluded. Basic information was collected and the development of ATBs was examined during follow-up. The life-table method was used to calculate cumulative incidence rates. Potential risk factors were analyzed through Cox regression analysis., Results: A total of 1680 patients with LTBI were recruited in the follow-up cohort, and 377 (22.44%) patients dropped out. With a median follow-up time of 81 months [interquartile range (IQR):61-93], 19 of 1303 patients with LTBI developed ATB. The 1-year incidence of ATB was 614 per 100,000 individuals [95%confidence interval (95% CI):584-644]. Over 5-year period, the cumulative incidence of ATB was 1496 per 100,000 [95% CI:1430-1570], and the incidence density was 240 per 100,000 person-years[95% CI:144-375]. In the Cox regression model, exposure of pulmonary tuberculosis (PTB) [adjusted hazard ratio (aHR)=10.557, 95% CI:2.273-49.031], maximum daily dosage of glucocorticoids (GCs)≥ 50 mg/d (aHR=2.948, 95% CI:1.122-7.748), leflunomide (LEF) treatment (aHR=8.572, 95% CI:2.222 -33.070), anemia (aHR=2.565, 95% CI:1.015-6.479) and T-SPOT.TB level≥300SFCs/10 6 PBMCs (aHR=4.195, 95% CI:1.365-12.892) were independent risk factors for ATB development in LTBI patients., Conclusion: The incidence of ATB is significantly higher in hospitalized patients with LTBI than in the general population. The exposure history of PTB, maximum daily dosage of GCs≥ 50 mg/day, LEF treatment, anemia, and T-SPOT.TB level≥300SFCs/10 6 PBMCs, were the risk factors of tuberculosis reactivation. Hospitalized LTBI patients with the above factors may need TPT., Competing Interests: The authors declare no conflicts of interest in this work., (© 2024 Liu et al.)

Objective: The aim of this study was to investigate the clinical traits and consequences of systemic lupus erythematosus (SLE) complicated by active cytomegalovirus (CMV) infection., Methods: This retrospective review involved the examination of medical records for patients diagnosed with SLE who had an active CMV infection at the time of their discharge from Peking Union Medical College Hospital between June 2016 and December 2022. The consistency between plasma CMV deoxyribonucleic acid (DNA) viral load and pp65 antigenemia was analyzed using the chi-square test. Related factors for CMV disease in SLE complicated by active CMV infection patients were analyzed by univariate analysis and multivariable stepwise logistic regression. Cox hazards regression analysis was used to determine predictors for all-cause mortality and CMV recurrence within 3 months., Results: A total of 206 patients were enrolled in this study. Of the 123 patients who were detected with both plasma CMV DNA viral load and pp65 antigenemia within an interval not exceeding 72 h, the consistency between plasma CMV DNA viral load and pp65 antigenemia was not good (Kappa = -0.304, p < 0.001). Plasma CMV DNA viral load ≥ 1,600 copies/mL [odds ratio (OR) 4.411, 95% CI 1.871-10.402, p = 0.001], current glucocorticoids dose (equivalent to prednisolone) ≥60 mg/d (OR 2.155, 95% CI 1.071-4.334, p = 0.031), and elevated alanine transaminase (OR 3.409, 95% CI 1.563-7.435, p = 0.002) were significant clinical clues indicating CMV disease in SLE. Multivariable Cox hazards regression analysis showed that CMV organ involvement [hazard ratio (HR) 47.222, 95% CI 5.621-396.689, p < 0.001], SLE multi-system involvement (HR 1.794, 95% CI 1.029-3.128, p = 0.039), and elevated hypersensitive C-reactive protein (hsCRP) (HR 5.767, 95% CI 1.190-27.943, p = 0.030) were independent risk factors for 3-month all-cause mortality. CMV organ involvement (HR 3.404, 95% CI 1.074-10.793, p = 0.037) was an independent risk factor for CMV recurrence within 3 months., Conclusion: In SLE patients, plasma CMV DNA viral load seemed to have a higher value in the diagnosis of CMV disease; patients with CMV organ involvement, SLE multi-system involvement, and elevated hsCRP might have a higher risk of 3-month all-cause mortality; and patients with CMV organ involvement might have a higher risk of CMV recurrence within 3 months., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Zhang, Liu, Liu, Zhao, Zhou, Ruan, Shi and Liu.)

The relation between perceived general stress and problematic mobile phone use (PMPU) has been well established. With the outbreak of the coronavirus disease (COVID-19), the present study was designed to examine the association between perceived stress of COVID-19 as a kind of event-related stress and PMPU, and the mechanisms underlying this relation. Participants were 724 adolescents ranging from 12 to 16 years old ( M  = 13.28, SD  = 1.05) who completed four online questionnaires addressing perceived stress of COVID-19, search for meaning in life, escapism motivation, and PMPU. The results revealed that escapism motivation mediated the relationship between perceived stress of COVID-19 and PMPU. In addition, search for meaning in life played a moderating role between perceived stress of COVID-19 and escapism motivation. These findings extend the literature by addressing how and under what conditions perceived stress of COVID-19 can contribute to PMPU. We discussed the implications for developing targeted intervention programs aimed at reducing PMPU among adolescents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jiang and Zhang.)

Background: More efficient and convenient diagnostic method is a desperate need to reduce the burden of tuberculosis (TB). This study explores the multiple cytokines secretion based on QuantiFERON-TB Gold Plus (QFT-Plus), and screens for optimal cytokines with diagnostic potential to differentiate TB infection status., Methods: Twenty active tuberculosis (ATB) patients, fifteen patients with latent TB infection (LTBI), ten patients with previous TB and ten healthy controls (HC) were enrolled. Whole blood samples were collected and stimulated by QFT-Plus TB1 and TB2 antigens. The levels of IFN-γ, TNF-α, IL-2, IL-6, IL-5, IL-10, IP-10, IL-1Ra, CXCL-1 and MCP-1 in supernatant were measured by Luminex bead-based multiplex assays. The receiver operating characteristic curve was used to evaluate the diagnostic accuracy of cytokine for distinguishing different TB infection status., Results: After stimulation with QFT-Plus TB1 and TB2 antigens, the levels of all cytokines, except IL-5 in TB2 tube, in ATB group were significantly higher than that in HC group. The levels of IL-1Ra concurrently showed the equally highest AUC for distinguishing TB infection from HC, followed by the levels of IP-10 in both TB1 tube and TB2 tube. Moreover, IP-10 levels displayed the largest AUC for distinguishing ATB patients from non-ATB patients. Meanwhile, the levels of IP-10 also demonstrated the largest AUC in both TB1 tube and TB2 tube for distinguishing ATB patients from LTBI., Conclusions: In addition to conventional detection of IFN-γ, measuring IP-10 and IL-1Ra based on QFT-Plus may have the more tremendous potential to discriminate different TB infection status., (© 2024. The Author(s).)

Competing Interests: The authors declare that they have no conflict of interest.

Competing Interests: The authors declare that they have no conflict of interest.

Competing Interests: The authors declare that they have no conflict of interest.

Introduction: Active tuberculosis (ATB), instigated by Mycobacterium tuberculosis (M.tb), rises as a primary instigator of morbidity and mortality within the realm of infectious illnesses. A significant portion of M.tb infections maintain an asymptomatic nature, recognizably termed as latent tuberculosis infections (LTBI). The complexities inherent to its diagnosis significantly hamper the initiatives aimed at its control and eventual eradication., Methodology: Utilizing the Gene Expression Omnibus (GEO), we procured two dedicated microarray datasets, labeled GSE39940 and GSE37250. The technique of weighted correlation network analysis was employed to discern the co-expression modules from the differentially expressed genes derived from the first dataset, GSE39940. Consequently, a pyroptosis-related module was garnered, facilitating the identification of a pyroptosis-related signature (PRS) diagnostic model through the application of a neural network algorithm. With the aid of Single Sample Gene Set Enrichment Analysis (ssGSEA), we further examined the immune cells engaged in the pyroptosis process in the context of active ATB. Lastly, dataset GSE37250 played a crucial role as a validating cohort, aimed at evaluating the diagnostic prowess of our model., Results: In executing the Weighted Gene Co-expression Network Analysis (WGCNA), a total of nine discrete co-expression modules were lucidly elucidated. Module 1 demonstrated a potent correlation with pyroptosis. A predictive diagnostic paradigm comprising three pyroptosis-related signatures, specifically AIM2, CASP8, and NAIP, was devised accordingly. The established PRS model exhibited outstanding accuracy across both cohorts, with the area under the curve (AUC) being respectively articulated as 0.946 and 0.787., Conclusion: The present research succeeded in identifying the pyroptosis-related signature within the pathogenetic framework of ATB. Furthermore, we developed a diagnostic model which exuded a remarkable potential for efficient and accurate diagnosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Zhang, Wu, Liu, Li and Chen.)

Introduction: The role of submucosal injection during cold snare polypectomy (CSP) remains uncertain. In this study, we investigated the impact of submucosal saline injection during CSP for colorectal polyps sized 3-9 mm., Methods: This was a multicenter randomized controlled trial conducted in 6 Chinese centers between July and September 2020 (ChiCTR2000034423). Patients with nonpedunculated colorectal polyps sized 3-9 mm were randomized in a 1:1 ratio to either CSP with submucosal injection (SI-CSP) or conventional CSP (C-CSP). The primary outcome was the incomplete resection rate (IRR). Secondary outcomes included procedure time, intraprocedural bleeding, delayed bleeding, and perforation., Results: One hundred fifty patients with 234 polyps in the SI-CSP group and 150 patients with 216 polyps in the C-CSP group were included in the analysis. The IRR was not decreased in the SI-CSP group compared with that in the C-CSP group (1.7% vs 1.4%, P = 1.000). The median procedure time in the SI-CSP group was significantly longer than that in the C-CSP group (108 seconds vs 48 seconds, P < 0.001). The incidences of intraprocedural bleeding and delayed bleeding were not significantly different between the 2 groups ( P = 0.531 and P = 0.250, respectively). There was no perforation in either group., Discussion: Submucosal saline injection during CSP for colorectal polyps sized 3-9 mm did not decrease the IRR or reduce adverse events but prolonged the procedure time., (Copyright © 2023 by The American College of Gastroenterology.)

Silicosis is an irreversible chronic pulmonary disease caused by long-term inhalation and deposition of silica particles, which is currently incurable. The exhaustion of airway epithelial stem cells plays a pathogenetic role in silicosis. In present study, we investigated therapeutic effects and potential mechanism of human embryonic stem cell (hESC)-derived MSC-likes immune and matrix regulatory cells (IMRCs) (hESC-MSC-IMRCs), a type of manufacturable MSCs for clinical application in silicosis mice. Our results showed that the transplantation of hESC-MSC-IMRCs led the alleviation of silica-induced silicosis in mice, accompanied by inhibiting epithelia-mesenchymal transition (EMT), activating B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi1) signaling and airway epithelial cell regeneration. In consistence, the secretome of hESC-MSC-IMRC exhibited abilities to restore the potency and plasticity of primary human bronchial epithelial cells (HBECs) proliferation and differentiation following the SiO 2 -induced HBECs injury. Mechanistically, the secretome resolved the SiO 2 -induced HBECs injury through the activation of BMI1 signaling and restoration of airway basal cell proliferation and differentiation. Moreover, the activation of BMI1 significantly enhanced the capacity of HBEC proliferation and differentiation to multiple airway epithelial cell types in organoids. Cytokine array revealed that DKK1, VEGF, uPAR, IL-8, Serpin E1, MCP-1 and Tsp-1 were the main factors in the hESC-MSC-IMRC secretome. These results demonstrated a potential therapeutic effect of hESC-MSC-IMRCs and their secretome for silicosis, in part through a mechanism by activating Bmi1 signaling to revert the exhaustion of airway epithelial stem cells, subsequentially enhance the potency and plasticity of lung epithelial stem cells., (© 2023 Wiley Periodicals LLC.)

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, with high morbidity and mortality worldwide. Although the dysregulation of BARX1 expression has been shown to be associated with malignant cancers, including NSCLC, the underlying mechanism remains elusive. In this study, we identified BARX1 as a common differentially expressed gene in lung squamous cell carcinoma and adenocarcinoma. Importantly, we uncovered a novel mechanism behind the regulation of BARX1, in which ZFP36 interacted with 3'UTR of BARX1 mRNA to mediate its destabilization. Loss of ZFP36 led to the upregulation of BARX1, which further promoted the proliferation, migration and invasion of NSCLC cells. In addition, the knockdown of BARX1 inhibited tumorigenicity in mouse xenograft. We demonstrated that BARX1 promoted the malignant phenotypes by transactivating a set of master oncogenes involved in the cell cycle, DNA synthesis and metastasis. Overall, our study provides insights into the mechanism of BARX1 actions in NSCLC and aids a better understanding of NSCLC pathogenesis., (© 2023. The Author(s).)

The objectives of this study were to screen for latent tuberculosis infection (LTBI) among patients with systemic lupus erythematosus (SLE) using the T-SPOT.TB assay and to identify factors affecting the assay results. SLE patients were enrolled from 13 tertiary hospitals in eastern, central, and western China from September 2014 to March 2016 and were screened using the T-SPOT.TB assay to detect LTBI. Basic information about the subjects was collected, including gender, age, body mass index (BMI), course of disease, evidence of previous tuberculosis, Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, and the use of glucocorticoids and immunosuppressants. Univariate analysis and multivariable logistic regression were performed to identify factors affecting the results of the T-SPOT.TB assay. In all, 2,229 SLE patients were screened using the T-SPOT.TB assay, of whom 334 patients tested positive, yielding a positivity rate of 15% (95% confidence interval [CI], 13.5% to 16.5%). The positivity rate was higher in male than female patients and had an increasing trend with age. Multivariable logistic regression analysis showed that patients over 40 (odds ratio [OR], 1.65; 95% CI, 1.29 to 2.10) and with evidence of previous tuberculosis (OR, 4.43; 95% CI, 2.81 to 6.99) were more likely to have positive T-SPOT.TB results, while patients with a SLEDAI-2K score of ≥10 (OR, 0.61; 95% CI, 0.43 to 0.88), a glucocorticoid dose of ≥60 mg/d (OR, 0.62; 95% CI, 0.39 to 0.98), leflunomide (LEF) treatment (OR, 0.51; 95% CI, 0.29 to 0.88), or tacrolimus (FK506) treatment (OR, 0.40; 95% CI, 0.16 to 1.00) were more likely to have negative T-SPOT.TB results. The frequencies of CFP-10-specific gamma interferon (IFN-γ)-secreting T cells were significantly lower in SLE patients with severe disease activity or high-dose glucocorticoids ( P  < 0.05). The positivity rate of the T-SPOT.TB assay was 15% among SLE patients. Severe, active SLE disease and the use of high-dose glucocorticoids and some types of immunosuppressants are likely to result in negative T-SPOT.TB results. For SLE patients with the above conditions, diagnosing LTBI based on a positive T-SPOT.TB result may lead to underestimation of the prevalence. IMPORTANCE The burden of tuberculosis and systemic lupus erythematosus in China ranks among the top three in the world. Therefore, active screening for LTBI and preventive intervention in SLE patients are of great significance in China. In view of the lack of relevant data in a large sample, we conducted a multicenter, cross-sectional study using T-SPOT.TB as a screening method for LTBI, to investigate the prevalence of LTBI and analyze the factors affecting the results of the T-SPOT.TB assay in SLE patients. Our study showed that the overall positivity rate of the T-SPOT.TB assay in SLE patients was 15.0%, which was lower than the estimated LTBI prevalence in the general population in China (~20%). For SLE patients with severe, active disease, high-dose glucocorticoids, and some types of immunosuppressants, a diagnosis of LTBI based on only positive T-SPOT.TB results may lead to underestimation of the prevalence., Competing Interests: The authors declare no conflict of interest.

Objectives: Both burdens of tuberculosis (TB) and systemic lupus erythematosus (SLE) in China are ranked as top three in the world. SLE patients are at high risk for TB, but so far, there are no guidelines for TB prevention and management targeting this population in China. This study aims to investigate the incidence of active tuberculosis (ATB) and to explore the risk factors for developing ATB in SLE patients, and to provide evidence for TB prevention and management for SLE patients in China., Methods: A multi-center prospective cohort study was conducted. SLE patients were enrolled from clinics and wards of 13 tertiary hospitals in Eastern, Middle, and Western China from September 2014 to March 2016. Baseline demographic features, TB infection status, clinical information, and laboratory data were collected. ATB development was examined during follow-up visits. Kaplan-Meier method was applied to plot survival curves, and Log-rank test was used to evaluate differences. Cox proportional-hazards model was used to explore the risk factors for ATB development., Results: With a median follow-up time of 58 months [interquartile range (IQR): 55-62], 16 out of 1361 SLE patients developed ATB. The 1-year incidence of ATB was 368 [95% confidence interval (CI): 46-691] per 100,000. Over a 5-year period, the cumulative incidence of ATB was 1141 [95% CI: 564-1718] per 100,000, and the incidence density was 245 per 100,000 person-years. Cox regression models were constructed with maximum daily dose of glucocorticoids (GCs) as a continuous variable and a categorical variable, respectively. In model 1, maximum daily dose of GCs (pills per day) [adjusted hazard ratio (aHR)=1.16, 95%CI: 1.04-1.30, p=0.010] and TB infection (aHR=8.52, 95%CI: 3.17-22.92, p<0.001) were independent risk factors for ATB development. In model 2, maximum daily dose of GCs≥30 mg/d (aHR =4.81, 95%CI: 1.09-22.21, P=0.038) and TB infection (aHR=8.55, 95%CI: 3.18-23.00, p<0.001] were independent risk factors for ATB development., Conclusions: SLE patients had a higher incidence of ATB compared to the general population. The risk of developing ATB was even higher with increased daily dose of GCs or in a status of TB infection, in which case TB preventive treatment should be considered., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Zou, Jiang, Xie, Liu, Yang, Cao, Li, Sun, Zhang, Zhao, Zeng, Shi and Liu.)

Effective wound sealing is key to prevent postoperative complications arising from gastric endoscopic submucosal dissection (ESD). Accurate delivery of the adhesive to wet and dynamic tissues and rapid action of the adhesive onsite should be considered for endoscopic operation. A hybrid dry powder (HDP) strategy, characterized by decoupling of powder gelation and tissue adhesion, for rapid sealing of wet tissues is presented. HDPs carrying oppositely charged polyelectrolytes become a hydrogel layer over the target tissue by absorbing the surrounding water and forming strong electrostatic interactions between heterogeneous components. Strong adhesion is realized through hydrogen bonding between the adhesive component, poly(acrylic acid), and the tissue. Wet tissue adhesion can be achieved in a few seconds (adhesion strength of ∼30 kPa to porcine skin). Notably, the HDP-assembled hydrogel can maintain a low swelling rate and resist degradation in acidic aqueous environments (pH 1). Furthermore, HDPs can be delivered to target tissues by spraying via an endoscope. The results of in vivo experiments indicate that healing of gastric ESD perforations by sealing with the powder-assembled hydrogel is as effective as that by sealing with clips. This strategy is expected to facilitate the development of fast-acting hydrogel-based adhesives for endoscopic operation.

Poly(lactic acid) (PLA) microneedles have been explored extensively, but the current regular fabrication strategy, such as thermoforming, is inefficient and poorly conformable. In addition, PLA needs to be modified as the application of microneedle arrays made of pure PLA is limited because of their easy tip fracture and poor skin adhesion. For this purpose, in this article, we reported a facile and scalable strategy to fabricate the microneedle arrays of the blend of PLA matrix and poly(p-dioxanone) (PPDO) dispersed phase with complementary mechanical properties through microinjection molding technology. The results showed that the PPDO dispersed phase could be in situ fibrillated under the effect of the strong shear stress field generated in micro-injection molding. These in situ fibrillated PPDO dispersed phases could hence induce the formation of the shish-kebab structures in the PLA matrix. Particularly for PLA/PPDO (90/10) blend, there are the densest and most perfect shish-kebab structures formed. The above microscopic structure evolution could be also advantageous to the enhancement in the mechanical properties of microparts of PLA/PPDO blend (tensile microparts and microneedle arrays), e.g., the elongation at break of the blend is almost double that of pure PLA while still maintaining the high stiffness (Young's modulus of 2.7 GPa) and the high strength (tensile strength of 68.3 MPa) in the tensile test, and relative to pure PLA, there is 100% or more increase in the load and displacement of microneedle in the compression test. This could open up new spaces for expanding the industrial application of the fabricated microneedle arrays.

Premature ovarian insufficiency (POI) is a complex disease which causes amenorrhea, hypergonadotropism and infertility in patients no more than 40 years old. Recently, several studies have reported that exosomes have the potential to protect ovarian function using a POI-like mouse model induced by chemotherapy drugs. In this study, the therapeutic potential of exosomes derived from human pluripotent stem cell-mesenchymal stem cells (hiMSC exosomes) was evaluated through a cyclophosphamide (CTX)-induced POI-like mouse model. POI-like pathological changes in mice were determined by serum sex-hormones levels and the available number of ovarian follicles. The expression levels of cellular proliferation proteins and apoptosis-related proteins in mouse ovarian granulosa cells were measured using immunofluorescence, immunohistochemistry and Western blotting. Notably, a positive effect on the preservation of ovarian function was evidenced, since the loss of follicles in the POI-like mouse ovaries was slowed. Additionally, hiMSC exosomes not only restored the levels of serum sex hormones, but also significantly promoted the proliferation of granulosa cells and inhibited cell apoptosis. The current study suggests that the administration of hiMSC exosomes in the ovaries can preserve female-mouse fertility.

Objective: To establish an acute kidney injury (AKI) prediction model in patients after cardiac surgery by extreme gradient boosting (XGBoost) machine learning model, and to explore the risk and protective factors for AKI in patients after cardiac surgery., Methods: All patients who underwent cardiac surgery in Medical Information Mart for Intensive Care-III (MIMIC-III) database were enrolled, and they were divided into AKI group and non-AKI group according to whether AKI developed within 14 days after cardiac surgery. Their clinical characteristics were compared. Based on five-fold cross-validation, XGBoost and Logistic regression were used to establish the prediction model of AKI after cardiac surgery. And the area under the receiver operator characteristic curve (AUC) of the models was compared. The output model of XGBoost was interpreted by Shapley additive explanations (SHAP)., Results: A total of 6 912 patients were included, of which 5 681 (82.2%) developed AKI within 14 days after the operation, and 1 231 (17.8%) did not. Compared with the non-AKI group, the main characteristics of AKI group included older age [years: 68.0 (59.0, 76.0) vs. 62.0 (52.0, 71.0)], higher incidence of emergency admission and complicated with obesity and diabetes (52.4% vs. 47.8%, 9.0% vs. 4.0%, 32.0% vs. 22.2%), lower respiratory rate [RR; bpm: times/min: 17.0 (14.0, 20.0) vs. 19.0 (15.0, 22.0)], lower heart rate [HR; bpm: 80.0 (67.0, 89.0) vs. 82.0 (71.5, 93.0)], higher blood pressure [mmHg (1 mmHg ≈ 0.133 kPa): 80.0 (70.7, 90.0) vs. 78.0 (70.0, 88.0)], higher hemoglobin (Hb), blood glucose, blood K + level and serum creatinine [SCr; Hb (g/L): 122.0 (109.0, 136.0) vs. 120.0 (106.0, 135.0), blood glucose (mmol/L): 7.3 (6.1, 8.9) vs. 6.8 (5.7, 8.5), blood K + level (mmol/L): 4.2 (3.9, 4.7) vs. 4.2 (3.8, 4.6), SCr (μmol/L): 88.4 (70.7, 106.1) vs. 79.6 (70.7, 97.2)], lower albumin (ALB) and triacylglycerol [TG; ALB (g/L): 38.0 (35.0, 41.0) vs. 39.0 (37.0, 42.0), TG (mmol/L): 1.4 (1.0, 2.0) vs. 1.5 (1.0, 2.2)] as well as higher incidence of multiple organ dysfunction syndrome (MODS) and sepsis (30.6% vs. 16.2%, 3.3% vs. 1.9%), with significant differences (all P < 0.05). In the output model of Logistic regression, important predictors were lactic acid [Lac; odds ratio (OR) = 1.062, 95% confidence interval (95%CI) was 1.030-1.100, P = 0.005], obesity (OR = 2.234, 95%CI was 1.900-2.640, P < 0.001), male (OR = 0.858, 95%CI was 0.794-0.928, P = 0.049), diabetes (OR = 1.820, 95%CI was 1.680-1.980, P < 0.001) and emergency admission (OR = 1.278, 95%CI was 1.190-1.380, P < 0.001). Receiver operator characteristic curve (ROC curve) analysis showed that the AUC of the Logistic regression model for predicting AKI after cardiac surgery was 0.62 (95%CI was 0.61-0.67). After optimizing the XGBoost model parameters by grid search combined with five-fold cross-validation, the model was trained well with no overfitting or overfitting. ROC analysis showed that the AUC of XGBoost model for predicting AKI after cardiac surgery was 0.77 (95%CI was 0.75-0.80), which was significantly higher than that of Logistic regression model (P < 0.01). After SHAP treatment, in the output model of XGBoost, age and ALB were the most important predictors of the final outcome, where age was the risk factor (average |SHAP value| was 0.434), and ALB was the protective factor (average |SHAP value| was 0.221)., Conclusions: Age is an important risk factor for AKI after cardiac surgery, and ALB is a protective factor. The performance of machine learning in predicting cardiac and vascular surgery-associated AKI is better than the traditional Logistic regression. XGBoost can analyze the more complex relationship between variables and outcomes, and can predict the risk of postoperative AKI more accurately and individually.

Introduction: The detailed association between albumin levels and mortality has not been studied in critically ill children. The aim of this study was to reveal an association between albumin levels in detail and mortality in critically ill children., Materials and Methods: We retrospectively collected data from children admitted to four pediatric intensive care units (PICUs) in China between January 2015 and October 2020. Restricted cubic spline curves based on logistic regression models were generated to evaluate the detailed associations between serum albumin levels and PICU mortality. Threshold effect analysis was performed using two piecewise regression models., Results: The study included 9,123 children. The overall mortality was 5.3%. The detailed association between serum albumin levels and the risk of mortality followed a U-shape. The risk of mortality decreased with increasing serum albumin levels (OR = 0.919; 95% CI: 0.886, 0.954) in children with serum albumin levels < 43.2 g/L and increased with increasing serum albumin levels (OR = 1.174; 95% CI: 1.044, 1.316) in children with serum albumin levels ≥ 43.2 g/L., Conclusion: There was a U-shaped association between serum albumin levels and mortality in critically ill children in the PICU., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Zhang, Wei, Feng, Yang, Zhang, Lu, Gui, Zhou, Yang, Zhou, Zhou, Wang, Chen and Ji.)

To improve the quality characteristics of noodles and enrich nutritional value, Tremella fuciformis (TF) powder was incorporated into noodles. Tremella fuciformis (TF) is an edible fungus with rich nutritional value, and TF gel has good viscosity properties. This paper explored the effect of TF on noodle quality, and compared the difference between TF and three hydrocolloids: sodium alginate (SA), guar gum (GG) and xanthan gum (XG). The results showed that TF could significantly (p < 0.05) increase the hardness, adhesiveness and chewiness of noodles, and showed a decreasing trend for additions greater than 3%. The addition of 3% TF enhanced storage modulus (G′), loss modulus (G″) and elasticity of dough. The addition of 3% TF also increased α-helix and β-sheet content, and degradation temperature in noodles. Meanwhile, it elevated the deeply bound water content and retarded water mobility. In addition, the content of slowly digestible starch and resistant starch in the noodles increased with the addition of 3% TF. It was found that the effect of 3% TF on the above data was not different from the effects of the three hydrocolloids (respectively, their optimal additions), and improved the quality characteristics of the noodles. The results provide guidance for the application of TF and the development of a new natural hydrocolloid and nutritionally fortified noodles.

S. chinensis is a typical monoecious plant, and the number and development of female flowers determines the yield of S. chinensis . Due to a lack of genetic information, the molecular mechanism of sex differentiation in S. chinensis remains unclear. In this study, the combination of scanning electron microscopy (SEM) and RNA sequencing (RNA-seq) was used to understand the way of sex differentiation of S. chinensis and to mine the related genes of sex determination. The result shows the development of male and female S. chinensis flowers was completed at the same time, the unisexual S. chinensis flowers did not undergo a transition stage between sexes, and sex may have been determined at an early stage in flower development. The results of the gene function analysis of the plant hormone signaling pathway and sucrose metabolism pathway suggest that auxin and JA could be the key hormones for sex differentiation in S. chinensis , and sucrose may promote pollen maturation at the later stage of male flower development. Two AGAMOUS ( GAG ) genes, 10 AGAMOUS-like MADS-box (AGLs) genes, and the MYB, NAC, WRKY, bHLH, and Trihelix transcription factor families may play important roles in sex determination in S. chinensis . Taken together, the present findings provide valuable genetic information on flower development and sex determination in S. chinensis .

Objective: This study aimed to compare the accuracy of QuantiFERON-TB Gold Plus (QFT-Plus) and T-SPOT.TB for diagnosing active tuberculosis (ATB) in febrile patients, to explore influencing factors of positive results and to verify the potential value of QFT-Plus in the identification of ATB and latent tuberculosis infection (LTBI)., Methods: A total of 240 febrile patients with ATB (n = 80) and non-ATB (n = 160) were recruited to assess the accuracy of QFT-Plus and T-SPOT.TB for diagnosing ATB. Multivariable logistic regression was used to analyze the influencing factors of positive results., Results: The proportion of indeterminate results (ITRS) in QFT-Plus and T-SPOT.TB were 3.3% and 0%, respectively. The consistency between the results of the QFT-Plus and T-SPOT.TB was substantial. The area under the receiver operating characteristic curve (AUROC) of the QFT-Plus and T-SPOT.TB for diagnosing ATB was 0.792 and 0.849 (p = 0.070), respectively. The sensitivity of differentiating ATB from non-ATB was 92.2% in QFT-Plus versus 95.0% in T-SPOT.TB. The influencing factors of T-SPOT.TB positive result were male (odds ratio (OR) = 2.33, 95% confidence interval (CI) 1.27-4.26, p = 0.006), evidence of previous TB (OR 11.36, 95% CI 4.62-27.94, p < 0.001), while male (OR = 3.17, 95% CI 1.73-5.84, p < 0.001), evidence of previous TB (OR = 7.58, 95% CI 3.60-15.98, p <0.001), and use of immunosuppressant (OR = 0.49, 95% CI 0.260.94, p = 0.030) were influencing factors for QFT-Plus positive result. There was no significant difference in QFT-Plus in differentiating ATB from LTBI in febrile patients., Conclusion: There was no significant difference between QFT-Plus and T-SPOT.TB for diagnosing ATB in febrile patients. QFT-Plus is prone to ITRS. The influencing factors including males, evidence of the previous TB, and use of immunosuppressant should be considered when interpreting positive results., (© 2022 The Authors. Journal of Evidence-Based Medicine published by Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.)

Background: The non-invasive preoperative diagnosis of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) is vital for precise surgical decision-making and patient prognosis. Herein, we aimed to develop an MVI prediction model with valid performance and clinical interpretability., Methods: A total of 2160 patients with HCC without macroscopic invasion who underwent hepatectomy for the first time in West China Hospital from January 2015 to June 2019 were retrospectively included, and randomly divided into training and a validation cohort at a ratio of 8:2. Preoperative demographic features, imaging characteristics, and laboratory indexes of the patients were collected. Five machine learning algorithms were used: logistic regression, random forest, support vector machine, extreme gradient boosting (XGBoost), and multilayer perception. Performance was evaluated using the area under the receiver operating characteristic curve (AUC). We also determined the Shapley Additive exPlanation value to explain the influence of each feature on the MVI prediction model., Results: The top six important preoperative factors associated with MVI were the maximum image diameter, protein induced by vitamin K absence or antagonist-II, α-fetoprotein level, satellite nodules, alanine aminotransferase (AST)/aspartate aminotransferase (ALT) ratio, and AST level, according to the XGBoost model. The XGBoost model for preoperative prediction of MVI exhibited a better AUC (0.8, 95% confidence interval: 0.74-0.83) than the other prediction models. Furthermore, to facilitate use of the model in clinical settings, we developed a user-friendly online calculator for MVI risk prediction based on the XGBoost model., Conclusions: The XGBoost model achieved outstanding performance for non-invasive preoperative prediction of MVI based on big data. Moreover, the MVI risk calculator would assist clinicians in conveniently determining the optimal therapeutic remedy and ameliorating the prognosis of patients with HCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Zhang, Xin, Zhang, You, Bai, Zhou and Ying.)

Background: Acute kidney injury (AKI) is a serve and harmful syndrome in the intensive care unit. Comparing to the patients with AKI stage 1/2, the patients with AKI stage 3 have higher in-hospital mortality and risk of progression to chronic kidney disease. The purpose of this study is to develop a prediction model that predict whether patients with AKI stage 1/2 will progress to AKI stage 3., Methods: Patients with AKI stage 1/2, when they were first diagnosed with AKI in the Medical Information Mart for Intensive Care, were included. We used the Logistic regression and machine learning extreme gradient boosting (XGBoost) to build two models which can predict patients who will progress to AKI stage 3. Established models were evaluated by cross-validation, receiver operating characteristic curve, and precision-recall curves., Results: We included 25,711 patients, of whom 2130 (8.3%) progressed to AKI stage 3. Creatinine, multiple organ failure syndromes were the most important in AKI progression prediction. The XGBoost model has a better performance than the Logistic regression model on predicting AKI stage 3 progression. Thus, we build a software based on our data which can predict AKI progression in real time., Conclusions: The XGboost model can better identify patients with AKI progression than Logistic regression model. Machine learning techniques may improve predictive modeling in medical research., (© 2022. The Author(s).)

Erythronium japonicum Decne (Liliaceae) flowers in early spring after overwintering. Its sexual reproduction process includes an underground development process of floral organs, but the underlying molecular mechanisms are obscure. The present study is aimed at exploring the transcriptional changes and key genes involved at underground floral developmental stages, including flower primordium differentiation, perianth differentiation, stamen differentiation, and pistil differentiation in E. japonicum . Multistage high-quality transcriptomic data resulted in identifying putative candidate genes for underground floral differentiation in E. japonicum. A total of 174,408 unigenes were identified, 28,508 of which were differentially expressed genes (DEGs) at different floral developmental stages, while only 44 genes were identified with conserved regulation between different stages. Further annotation of DEGs resulted in the identification of 270 DEGs specific to floral differentiation. In addition, ELF3 , PHD , cullin 1 , SE14 , ZSWIM3 , GIGNATEA , and SERPIN B were identified as potential candidate genes involved in the regulation of floral differentiation. Besides, we explored transcription factors with differential regulation at different developmental stages and identified bHLH , FAR1 , mTERF , MYB-related , NAC , Tify , and WRKY TFs for their potential involvement in the underground floral differentiation process. Together, these results laid the foundation for future molecular works to improve our understanding of the underground floral differentiation process and its genetic regulation in E. japonicum., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Hongtao Wang et al.)

Background: Differential diagnosis of active tuberculosis (ATB) and latent tuberculosis infection (LTBI) has been a challenge for clinicians in high TB burden countries. The purpose of this study was to improve the accuracy of differential diagnosis of ATB and LTBI by using fluorescent immunospot (FluoroSpot) assay to detect specific Th1 cell immune responses. The novel mycobacterium tuberculosis (MTB) latency-associated antigens Rv1733c and synthetic long peptides derived from Rv1733c (Rv1733c SLP) were used based on virulence factors early secreting antigen target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10)., Methods: Fifty-seven ATB cases, including 20 pathogen-confirmed ATB and 37 clinically diagnosed ATB, and 36 LTBI cases, were enrolled between January and December 2017. FluoroSpot assay was used to detect the interferon γ (IFN-γ) and interleukin 2 (IL-2) secreted by the specific T cells after being stimulated with MTB virulence factors ESAT-6 and CFP-10, MTB latency-associated antigens Rv1733c and Rv1733c SLP. The receiver operating characteristic (ROC) curve was used to define the best cutoff value of latency-associated antigens in the use of differentiating ATB and LTBI. The sensitivity, specificity, predictive value, and likelihood ratio of ESAT-6 and CFP-10-FluoroSpot combined with latency-associated antigen in the differential diagnosis of ATB and LTBI were also calculated., Results: Following the stimulation with Rv1733c and Rv1733c SLP, the frequency of single IL-2-secreting T cells stimulated by Rv1733c SLP had the largest area under the ROC curve, which was 0.766. With a cutoff value of 1 (spot-forming cells [SFCs]/2.5 × 105 peripheral blood mononuclear cells) for frequency, the sensitivity and specificity of distinguishing ATB from LTBI were 72.2% and 73.7%, respectively. ESAT-6 and CFP-10-FluoroSpot detected the frequency and proportion of single IFN-γ-secreting T cells; the sensitivity and specificity of distinguishing ATB from LTBI were 82.5% and 66.7%, respectively. Combined with the frequency of single IL-2-secreting T cells stimulated by Rv1733c SLP on the basis of ESAT-6 and CFP-10-FluoroSpot, the sensitivity and specificity increased to 84.2% and 83.3%, respectively., Conclusion: Rv1733c SLP, combined with ESAT-6 and CFP-10, might be used as a candidate antigen for T cell-based tuberculosis diagnostic tests to differentiate ATB from LTBI., (Copyright © 2021 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Background: The differential diagnosis of active tuberculosis (ATB) and latent tuberculosis infection (LTBI) remains challenging in clinical practice. We aimed to evaluate the diagnostic accuracy of the IFN-γ/TNF-α FluoroSpot assay for differentiating ATB from LTBI., Methods: We conducted a pilot study of case-control design, using the FluoroSpot assay to simultaneously detect IFN-γ and TNF-α secretion at the single-cell level. The frequencies of antigen-specific single TNF-α-, total TNF-α-, single IFN-γ-, total IFN-γ- and dual IFN-γ/TNF-α-secreting T cells were detected. The optimal cutoffs value of frequencies for differentiating ATB from LTBI were determined according to receiver operating characteristic curve analysis. The sensitivity, specificity, predictive values (PV) and likelihood ratios (LR) of the FluoroSpot assay were calculated., Results: Thirty patients diagnosed microbiologically with ATB, 36 healthcare workers with LTBI and 36 healthy controls were enrolled. After stimulated by ESAT-6 or CFP-10 peptides, the median frequencies of single TNF-α-, total TNF-α-, single IFN-γ-, total IFN-γ- and dual IFN-γ/TNF-α-secreting T cells in ATB patients were all significantly higher than those in LTBI and HC groups (P < 0.01). The frequencies of total IFN-γ-secreting T cells detected by FluoroSpot assay correlated significantly with those of T-SPOT.TB (r = 0.910 for ESAT-6, P < 0.001, r = 0.845 for CFP-10, P < 0.001). After stimulated by ESAT-6 peptides, with total TNF-α-secreting T cells frequencies at a cut off value of 21 iSFCs/250,000 PBMCs, the sensitivity, specificity, PLR, NLR, PPV, NPV of IFN-γ/TNF-α FluoroSpot assay in differentiating ATB from LTBI were 96.7% (95%CI, 82.8-99.9%), 94.3% (95%CI, 80.8-99.3%), 16.92 (95%CI, 4.40-65.08), 0.04 (95%CI, 0.01-0.24), 93.6% (95%CI,78.6-99.2%) and 97.1% (95%CI, 84.7-99.9%), respectively. With the frequencies of total TNF-α- and total IFN-γ-secreting T cells stimulated by ESAT-6 peptides combined, the specificity was increased to 97.1%, and the positive likelihood ratio to 31.5. The combination with CFP-10 might not improve the diagnostic accuracy of the ESAT-6 for differentiating ATB from LTBI., Conclusions: IFN-γ/TNF-α FluoroSpot assay might have potential to help differentiate ATB from LTBI, but the findings need to be further verified by cross-sectional or prospective cohort studies.

As a momentous post-transcriptional regulator, microRNAs (miRNAs) are attracting more and more attention. The classical miRNAs regulated mechanism shows it binds to the targets' 3'UTR thus play the role in post-transcription. Meanwhile, single miRNA can target multiple genes, so those should compete to bind that miRNA. Vice versa, single gene can sponge mass of miRNAs as well. Thus the competitive endogenous RNAs (ceRNAs) hypothesis was put forward in 2011. The ceRNA hypothesis has made huge achievements, in particular in non-coding genes, which including long non-coding RNAs (lncRNAs), circle RNAs (circRNAs) and pseudogenes, even viral transcripts. It also contributed greatly to epigenetics development. However, an increasing number of controversies have occurred with applause. Based on this situation, this review introduces something in detail about the ceRNAs hypothesis achieved in lncRNAs, circRNAs, pseudogenes and viral transcripts, respectively. Meanwhile, it also covers controversy of the ceRNAs hypothesis.

SMARCA2, an evolutionarily conserved catalytic ATPase subunit of SWI/SNF complexes, has been implicated in development and diseases; however, its role in mammalian ovarian function and female fertility is unknown. Here, we identified and characterized the 3'-UTR of the porcine SMARCA2 gene and identified a novel adenylate number variation. Notably, this mutation was significantly associated with sow litter size traits and SMARCA2 levels, due to its influence on the stability of SMARCA2 mRNA in ovarian granulosa cells (GCs). Immunohistochemistry and functional analysis showed that SMARCA2 is involved in the regulation of follicular atresia by inhibiting GC apoptosis. In addition, miR-29c, a pro-apoptotic factor, was identified as a functional miRNA that targets SMARCA2 in GCs and mediates regulation of SMARCA2 expression via the NORFA -SMAD4 axis. Although a potential miR-29c-responsive element was identified within NORFA , negative regulation of miR-29c expression by NORFA was not due to activity as a competing endogenous RNA. In conclusion, our findings demonstrate that SMARCA2 is a candidate gene for sow litter size traits, because it regulates follicular atresia and GC apoptosis. Additionally, we have defined a novel candidate pathway for sow fertility, the NORFA -TGFBR2-SMAD4-miR-29c-SMARCA2 pathway.This article has an associated First Person interview with the first author of the paper., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Currently available Interferon-γ release assay cannot reliably differentiate active TB (ATB) from non-active TB (non-ATB). This study aimed to evaluate the diagnostic accuracy of the IFN-γ/IL-2 FluoroSpot assay, which can simultaneously detect IFN-γ and IL-2 secretion, for differentiating ATB from non-ATB. 191 suspected ATB patients with positive T-SPOT.TB results were consecutively recruited. 64 (33.5%) participants had ATB, including 22 (34.4%) microbiologically or histologically confirmed TB and 42 (65.6%) clinically diagnosed TB. 119 (62.3%) cases were non-ATB and 8 (4.2%) were clinically indeterminate. After being stimulated with ESAT-6 and CFP-10 antigens, the median frequency and proportion of IFN-γ + IL-2 - T cells were significantly higher in the ATB group than the non-ATB group (P < .001). The areas under the ROC curves of IFN-γ + IL-2 - T cells were larger than those of total IFN-γ + T cells (0.788 vs. 0.739, p = .323). With a cutoff value of 25 SFCs/250,000 PBMCs for frequency, sensitivity and specificity of this assay were 73.4% and 69.8% respectively. When combining the frequency and proportions of IFN-γ + IL-2 - T cells, the sensitivity and specificity were increased to 95.3% in parallel testing and 83.2% in serial testing respectively. In conclusion, IFN-γ/IL-2 FluoroSpot assay is conducive for the diagnosis of ATB in patients with positive T-SPOT.TB results., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The mechanism of adipocyte regulation specifically in muscle and the influence of muscle tissue on intramuscular fat deposition are unknown. Our previous studies have shown that myostatin, a myokine, is involved in inhibiting the differentiation of preadipocytes and may be a potential regulator that affects the deposition of intramuscular fat. Myostatin inhibited adipogenesis by downregulating the expression of glucocorticoid receptor (GR) in porcine preadipocytes. However, the mechanism of regulation is not yet clear. In this study, we demonstrate microRNA (miR-124-3p) mediates regulation of GR by myostatin. We found that miR-124-3p can target GR 3'-UTR and negatively regulate GR expression. We demonstrate that overexpression of miR-124-3p can reduce differentiation of 3T3-L1 cells by inhibiting GR, and vice versa. The expression of miR-124-3p was upregulated in 3T3-L1 cells treated with myostatin. Further study revealed that myostatin also promotes the expression of SMAD4 and its transfer and localization to the nucleus. The activated myostatin/SMAD4 signal promotes the expression of miR-124-3p by SMAD4 binding to the promoter region of miR-124-3p. When myostatin or SMAD4 activity is inhibited, the upregulation of miR-124-3p is also inhibited. All of these findings suggested that myostatin could inhibit adipogenic differentiation of 3T3-L1 cells by activating miR-124-3p to inhibit GR. These data may provide an explanation for how myostatin signaling affects intramuscular fat deposition in a tissue-specific manner.

In obesity and diabetes, intramuscular fat (IMF) content correlates markedly with insulin sensitivity, which makes IMF manipulation an area of therapeutic interest. Melatonin, an important circadian rhythm-regulating hormone, reportedly regulates fat deposition, but its effects on different types of adipose vary. Little is known about the role of melatonin in IMF deposition. Here, using intramuscular preadipocytes in pigs, we investigated to determine whether melatonin affects or regulates IMF deposition. We found that melatonin greatly inhibited porcine intramuscular preadipocyte proliferation. Although melatonin administration significantly upregulated the expression of adipogenic genes, smaller lipid droplets were formed in intramuscular adipocytes. Additional investigation demonstrated that melatonin promoted lipolysis of IMF by activating protein kinase A and the signaling of ERK1/2. Moreover, melatonin increased thermogenesis in intramuscular adipocytes by enhancing mitochondrial biogenesis and mitochondrial respiration. A mouse model, in which untreated controls were compared with mice that received 3 weeks of melatonin treatment, verified the effect of melatonin on IMF deposition. In conclusion, melatonin reduces IMF deposition by upregulating lipolysis and mitochondrial bioactivities. These data establish a link between melatonin signaling and lipid metabolism in mammalian models and suggest the potential for melatonin administration to treat or prevent obesity and related diseases., (Copyright © 2019 Liu et al.)

Objective s To investigate the positive rate of different hepatitis B virus (HBV) serological markers, and the demographic factors related to HBV infection.Methods We enrolled all patients tested for HBV serological markers, such as HBV surface antigen (HBsAg), HBV surface antibody (HBsAb), hepatitis B e antigen (HBeAg), hepatitis B e antibody (HBeAb), HBV core antibody (HBcAb), and HBV-DNA from July 2008 to July 2009 in Peking Union Medical College Hospital. The positive rate of each HBV serological marker was calculated according to gender, age, and de- partment, respectively. The positive rates of HBV-DNA among patients with positive HBsAg were also analyzed.Results Among 27 409 samples included, 2681 (9.8%) were HBsAg positive. When patients were divided into 9 age groups, the age-specific positive rate of HBsAg was 1.2%, 9.6%, 12.3%, 10.9%, 10.3%, 9.7%, 8.0%, 5.8%, and 4.3%, respectively. The positive rate of HBsAg in non-surgical department, surgical department, and health examination center was 16.2%,5.8%,and 4.7%, respectively. The positive rate of HBsAg of males (13.3%) was higher than that of females (7.3%, P=0.000). Among the 2681 HBsAg (+) patients, 1230 (45.9%) had HBV-DNA test, of whom 564 (45.9%) were positive. Patients with HBsAg (+), HBeAg (+), and HBcAg (+) result usually had high positive rate of HBV-DNA Results (71.8%, P=0.000).Conclusions Among this group of patients in our hospital, the positive rate of HBsAg was relatively high. Age group of 20-29, males, and patients in non-surgical departments were factors associated with high positive rate of HBsAg.

MicroRNAs (miRNAs) are important modulators of skeletal muscle development in multiple mammalian species, but their role in skeletal muscle growth in castrated male pigs has not been well studied. The aim of the present study was to determine the role of miRNAs in longissimus dorsi muscle under castration. Our results showed that castration caused a significant decrease in serum testosterone levels as well as carcass lean mass, but led to an increase in carcass fat mass. Moreover, miRNA expression profiles in skeletal muscle were significantly altered by castration, and seven differentially expressed miRNAs were discovered. More importantly, functional analysis suggested that these differentially expressed miRNAs and their targets are involved in the regulation of skeletal muscle contractile function and fat metabolism. Taken together, these results demonstrate altered miRNA expression in skeletal muscle of castrated male pigs, and suggest a potential mechanism underlying the effects of castration on porcine skeletal muscle growth., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Differential privacy has recently emerged in private statistical data release as one of the strongest privacy guarantees. Releasing synthetic data that mimic original data with Differential privacy provides a promising way for privacy preserving data sharing and analytics while providing a rigorous privacy guarantee. However, to this date there is no open-source tools that allow users to generate differentially private synthetic data, in particular, for high dimensional and large domain data. Most of the existing techniques that generate differentially private histograms or synthetic data only work well for single dimensional or low-dimensional histograms. They become problematic for high dimensional and large domain data due to increased perturbation error and computation complexity. We propose DPSynthesizer, a toolkit for differentially private data synthesization. The core of DPSynthesizer is DPCopula designed for high-dimensional and large-domain data. DPCopula computes a differentially private copula function from which synthetic data can be sampled. Copula functions are used to describe the dependence between multivariate random vectors and allow us to build the multivariate joint distribution using one-dimensional marginal distributions. DPSynthesizer also implements a set of state-of-the-art methods for building differentially private histograms, suitable for low-dimensional data, from which synthetic data can be generated. We will demonstrate the system using DPCopula as well as other methods with various data sets and show the feasibility, utility, and efficiency of various methods.

Objective: To evaluate the diagnostic efficiency of a T-cell interferon-γ release assay based on recombinant Mycobacterium tuberculosis (MTB) 11kD protein for diagnosing tuberculosis., Methods: This prospective study enrolled inpatients with suspected tuberculosis at PUMCH to examine the diagnostic sensitivity, specificity, predictive value (PV) and likelihood ratio (LR) of T-cell interferon-γ release assays based on recombinant MTB-11kD protein, early antigenic target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10) peptides (T-SPOT. TB). Test results were compared with final clinical and microbiological diagnoses., Results: Among 151 inpatients with suspected tuberculosis, 33 (21.9%) were microbiologically or clinically diagnosed as tuberculosis and 107 (70.9%) ruled out. And the remaining 11 (7.3%) patients were clinically indeterminate. The sensitivities of recombinant MTB-11kD-ELISPOT assay and T-SPOT. TB were 60.6%and 81.8%respectively (P = 0.057).Whereas, the specificity of recombinant MTB-11kD-ELISPOT assay was significantly higher than that of T-SPOT. TB (84.1%vs 72.9%, P = 0.046). The parallel testing increased the sensitivity to 84.9% and serial testing increased the specificity to 86.9%., Conclusion: The recombinant MTB-11kD-ELISPOT assay is more specific than T-SPOT. TB. And its combination with T-SPOT. TB may improve the diagnostic efficiency for tuberculosis.

Lung cancer is one of the main causes of cancer death worldwide. The cortactin gene, CTTN, may play a pivotal role in the proliferation and invasion of tumors. A microRNA (miR-182) was cloned and used to study the expression of CTTN and its regulatory effects on the proliferation and invasion of the lung cancer cell line, A549. Cortactin protein and CTTN mRNA expression decreased in A549 cells that were transfected with the miR-182 expression plasmid. A cell proliferation assay indicated that miR-182 expression affected cell cycle regulation and suppressed proliferation of lung cancer cells in vitro. In addition, xenograft experiments confirmed the suppression of tumor growth in vivo, which was due to the promotion of apoptosis. In conclusion, endogenous mature miR-182 expression may have an important role in the pathogenesis of lung cancer through its interference with the target gene CTTN by epigenetic modification.

Pancreatic and duodenal homeobox factor 1 (PDX-1) maintains β-cell function and differentiation via direct regulation of multiple islet cell genes. However, the molecular mechanisms involved in this process remain unknown. Here, we show that PDX-1 plays an important role in the induction of CD44+/CD105+ human amniotic fluid cells (HuAFCs) into functional pancreatic β-cell-like cells in vitro. CD44+/CD105+ HuAFCs were transfected with either siRNA targeting PDX-1 (siRNA-PDX-1) or mock plasmid (siRNA-MOCK). Following induction, siRNA-MOCK-transfected cells differentiated into β-cell-like cells that expressed multiple islet cell markers and produced insulin and C-peptide in a glucose-regulated manner. However, siRNA-PDX-1-transfected cells did not fully differentiate into β-cell-like cells. Further, we observed epigenetic changes at the PDX-1 gene locus in induced CD44(+)/CD105(+) HuAFCs. Therefore, CD44+/CD105+ HuAFCs could be a source of human pancreatic β-cell-like cells with potential uses in cell replacement therapy for diabetes.

Cytochrome c oxidase (COX) plays important roles in oxidative phosphorylation regulation and oxygen sensing transfer. In the present study, single-nucleotide polymorphisms (SNPs) in three mitochondrially coded subunit genes of COX were identified with the technique of single-strand conformation polymorphism in Tibet Chicken and four lowland chicken breeds-Dongxiang Chicken, Silky Chicken, Hubbard ISA White broiler, and Leghorn layer. In total, 14 SNPs were identified in the three genes of COX of the five chicken breeds, and 13 haplotypes were defined for the 14 SNPs. This work will afford reference for the further study on the association of COX with the adaptation to hypoxia.

We introduced the method of computer simulation in the studies of gravitational physiology. Based on work of Melchior (1994), we developed a mathematical model that can be used to stimulate cardiovascular responses to orthostatic stress (lower body negative pressure, LBNP). The model includes 7 sub-models: the redistribution of blood, the filling of left ventricle, left ventricle working, peripheral circulation, control of heart rate (HR), control of peripheral resistance and control of venous tone. Then we simulated the changes of blood pressure (BP) and heart rate during lower body negative pressure, and the results agreed well with the results of our human experiment. By using the developed model, we also simulated the effects of hypovolemia on the BP, HR and shock index during orthostatic stress. The simulation results indicate that the cardiovascular responses to orthostatic stress change significantly when the decrease of blood volume is more than 15% of the total blood volume. However, if the amount of the decrease of blood volume is less than 5% of the total blood volume, HR and BP could be maintained in normal range by the regulation of baroreflex during LBNP. Our simulation results suggest that hypovolemia may be the main cause of orthostatic intolerance induced by weightlessness.