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Yin-shan Jin,&ast; Yuan-qing Cui,&ast; Yan-ping Xu,&ast; Jie Chen, Xue-bao Zhang, Xiong Wang Department of Reproductive Medicine, Yantai Yuhuangding Hospital, Yantai, 264000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiong Wang, Department of Reproductive Medicine, Yantai Yuhuangding Hospital, No. 20, Yuhuangding East Road, Yantai, 264000, People’s Republic of China, Email wangxiong01903@163.comIntroduction: Varicocele is a dilatation of the internal spermatic vein and it is generally recognized as one cause of male infertility. This study aimed to analyze the roles of activating transcription factor 6 (ATF-6) in experimental varicocele-induced epididymal epithelial cells.Methods: Experimental left varicocele was established in rats through partial left renal vein ligation. At 8 weeks after surgery, the left epididymal damage was observed using H&E and TUNEL staining. The expressions of neutral α-glucosidase (NAG), ATF-6, tumor necrosis factor (TNF)-α, and phospho-nuclear factor (p-NF)-κB p65 (S536) in the left epididymis were measured by immunohistochemistry. ATF-6 silence in rat epididymal epithelial cells was established by ATF-6 siRNA transfection. The cells were treated with hypoxia for 24 h, and cell viability was measured by CCK-8, levels of NAG, TNF-α, and interleukin (IL)-8 in cells were measured by ELISA, levels of p-NF-κB p65 (S536)/NF-κB p65 protein in cells were measured by Western blotting.Results: The results showed that the experimental left varicocele induced hypertrophy and apoptosis of epididymal epithelial cells (p< 0.05), and decreased the expressions of NAG in the epididymal epithelial cells compared with the sham-operated control rats (p< 0.01). Meanwhile, the expressions of ATF-6, TNF-α, and p-NF-κB p65 (S536) were increased in the epididymal epithelial cells after the experimental left varicocele compared with the sham-operated control rats (p< 0.05). In the hypoxia-treated cells, ATF-6 silence increased the cell viability and decreased the levels of TNF-α, IL-8, and p-NF-κB p65 (S536) compared with the control cells (p< 0.05).Discussion: The ATF-6 pathway was activated in a rat’s left varicocele-induced epididymal damage. Inhibition of the ATF-6 pathway might be a possible novel therapeutic approach for left varicocele-induced epididymal damage.Keywords: epididymal neutral α-glucosidase, hypoxia, left varicocele, nuclear factor-kappa B p65, NF-κB p65

Tissue repair and regeneration present significant clinical challenges. Despite the array of treatments currently available in this domain, the urgent demand for innovative therapies persists, with the goal of enhancing patient quality of life. Recently, the application of botulinum neurotoxin type A (BoNT/A) has expanded within the realm of tissue repair and regeneration. This review critically examines the utilization of BoNT/A, specifically focusing on its vascular effects, potential in nerve regeneration, and contributions to bone healing. This analysis not only offers fresh insights into the diverse mechanisms of action of BoNT/A but also explores additional therapeutic possibilities for patients., Competing Interests: Declaration of Competing Interest ☒ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Li-Ping Chen reports financial support was provided by Hebei Medical Application Technology Tracking Project. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Purpose: Vibrio vulnificus (V. Vulnificus) infection is characterized by rapid onset, aggressive progression, and challenging treatment. Bacterial resistance poses a significant challenge for clinical anti-infection treatment and is thus the subject of research. Enhancing host infection tolerance represents a novel infection prevention strategy to improve patient survival. Our team initially identified cytochrome P4501A1 (CYP1A1) as an important target owing to its negative modulation of the body's infection tolerance. This study explored the superior effects of the CYP1A1 inhibitor bergamottin compared to antibiotic combination therapy on the survival of mice infected with multidrug-resistant V. Vulnificus and the protection of their vital organs., Methods: An increasing concentration gradient method was used to induce multidrug-resistant V. Vulnificus development. We established a lethal infection model in C57BL/6J male mice and evaluated the effect of bergamottin on mouse survival. A mild infection model was established in C57BL/6J male mice, and the serum levels of creatinine, urea nitrogen, aspartate aminotransferase, and alanine aminotransferase were determined using enzyme-linked immunosorbent assay to evaluate the effect of bergamottin on liver and kidney function. The morphological changes induced in the presence of bergamottin in mouse organs were evaluated by hematoxylin and eosin staining of liver and kidney tissues. The bacterial growth curve and organ load determination were used to evaluate whether bergamottin has a direct antibacterial effect on multidrug-resistant V. Vulnificus. Quantification of inflammatory factors in serum by enzyme-linked immunosorbent assay and the expression levels of inflammatory factors in liver and kidney tissues by real-time quantitative polymerase chain reaction were performed to evaluate the effect of bergamottin on inflammatory factor levels. Western blot analysis of IκBα, phosphorylated IκBα, p65, and phosphorylated p65 protein expression in liver and kidney tissues and in human hepatocellular carcinomas-2 and human kidney-2 cell lines was used to evaluate the effect of bergamottin on the nuclear factor kappa-B signaling pathway. One-way ANOVA and Kaplan-Meier analysis were used for statistical analysis., Results: In mice infected with multidrug-resistant V. Vulnificus, bergamottin prolonged survival (p = 0.014), reduced the serum creatinine (p = 0.002), urea nitrogen (p = 0.030), aspartate aminotransferase (p = 0.029), and alanine aminotransferase (p = 0.003) levels, and protected the cellular morphology of liver and kidney tissues. Bergamottin inhibited interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α expression in serum (IL-1β: p = 0.010, IL-6: p = 0.029, TNF-α: p = 0.025) and inhibited the protein expression of the inflammatory factors IL-1β, IL-6, TNF-α in liver (IL-1β: p = 0.010, IL-6: p = 0.011, TNF-α: p = 0.037) and kidney (IL-1β: p = 0.016, IL-6: p = 0.011, TNF-α: p = 0.008) tissues. Bergamottin did not affect the proliferation of multidrug-resistant V. Vulnificus or the bacterial load in the mouse peritoneal lavage fluid (p = 0.225), liver (p = 0.186), or kidney (p = 0.637)., Conclusion: Bergamottin enhances the tolerance of mice to multidrug-resistant V. Vulnificus infection. This study can serve as a reference and guide the development of novel clinical treatment strategies for V. Vulnificus., (Copyright © 2024 Chinese Medical Association. Production and hosting by Elsevier B.V. All rights reserved.)

The peroxisome is a versatile organelle that performs diverse metabolic functions. PEX3, a critical regulator of the peroxisome, participates in various biological processes associated with the peroxisome. Whether PEX3 is involved in peroxisome-related redox homeostasis and myocardial regenerative repair remains elusive. We investigate that cardiomyocyte-specific PEX3 knockout (Pex3-KO) results in an imbalance of redox homeostasis and disrupts the endogenous proliferation/development at different times and spatial locations. Using Pex3-KO mice and myocardium-targeted intervention approaches, the effects of PEX3 on myocardial regenerative repair during both physiological and pathological stages are explored. Mechanistically, lipid metabolomics reveals that PEX3 promotes myocardial regenerative repair by affecting plasmalogen metabolism. Further, we find that PEX3-regulated plasmalogen activates the AKT/GSK3β signaling pathway via the plasma membrane localization of ITGB3. Our study indicates that PEX3 may represent a novel therapeutic target for myocardial regenerative repair following injury., (© 2024. The Author(s).)

Aim: To explore the value of radiomics for predicting the expression of programmed death ligand 1 (PD-L1) in non-small-cell lung cancer (NSCLC) based on multiparameter spectral computed tomography (CT) images., Materials and Methods: A total of 220 patients with NSCLC were enrolled retrospectively and divided into the training (n=176) and testing (n=44) cohorts. The radiomics features were extracted from the conventional CT images, mono-energy 40 keV images, iodine density (ID) maps, Z-effective maps, and electron density maps. The logistic regression (LR) and support vector machine (SVM) algorithms were employed to build models based on radiomics signatures. The prediction abilities were qualified by the area under the curve (AUC) obtained from the receiver operating characteristic (ROC) curve. Internal validation was performed on the independent testing dataset., Results: The combined model for PD-L1 ≥1%, which consisted of the radiomics score (rad-score; p<0.0001), white blood cell (WBC; p=0.027) counts, and air bronchogram (p=0.003), reached the highest performance with the AUCs of 0.873 and 0.917 in the training and testing dataset, respectively, which was better than the radiomics model with the AUCs of 0.842 and 0.886. The combined model for PD-L1 ≥50%, which consisted of rad-score (p<0.0001) and WBC counts (p=0.027), achieved the highest performance in the training and testing dataset with AUCs of 0.932 and 0.903, respectively, which was better than the radiomics model with AUCs of 0.920 and 0.892, respectively., Conclusion: The radiomics model based on the multiparameter images of spectral CT can predict the expression level of PD-L1 in NSCLC. The combined model can obtain higher prediction efficiency and serves as a promising method for immunotherapy selection., (Copyright © 2024 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate the efficacy and safety of acute stent implantation during endovascular treatment for patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis. Methods: A retrospective analysis was carried out on 46 patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis who received endovascular treatment at the Strategic Support Force Medical Center from January 2015 to August 2022. Twenty-seven patients underwent balloon angioplasty alone and 19 patients underwent acute stent implantation. The baseline characteristics, modified thrombolysis in cerebral infarction (mTICI) score of the responsible vessels, modified Rankin scale (mRS) score 90 days after operation, incidence of symptomatic intracranial hemorrhage and mortality of the two groups were evaluated. Results: The proportion of effective recanalization of the offending vessels (mTICI≥2b) in the acute stenting group was slightly higher than that in the balloon angioplasty group (16/19 vs. 81.5%), but the difference was not statistically significant ( P >0.05). Besides, there was no significant difference in the median of mRS between the acute stenting group [3.0(0, 4.0)] and the balloon angioplasty group [4.0(1.0, 5.0)] 90 days after operation ( P >0.05). In terms of safety, the incidence of symptomatic intracranial hemorrhage and mortality were comparable between the two groups ( P >0.05). Conclusions: The effect of acute stent implantation during endovascular treatment for patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis is not inferior to that of balloon angioplasty, and it does not increase the risk of intracranial bleeding complications.

Key Message: Cathepsin B plays an important role that degrades the Rubisco large subunit RbcL in freezing stress. Programmed cell death (PCD) has been well documented in both development and in response to environmental stresses in plants, however, PCD induced by freezing stress and its molecular mechanisms remain poorly understood. In the present study, we characterized freezing-induced PCD and explored its mechanisms in Arabidopsis. PCD induced by freezing stress was similar to that induced by other stresses and senescence in Arabidopsis plants with cold acclimation. Inhibitor treatment assays and immunoblotting indicated that cathepsin B mainly contributed to increased caspase-3-like activity during freezing-induced PCD. Cathepsin B was involved in freezing-induced PCD and degraded the large subunit, RbcL, of Rubisco. Our results demonstrate an essential regulatory mechanism of cathepsin B for Rubisco degradation in freezing-induced PCD, improving our understanding of freezing-induced cell death and nitrogen and carbohydrate remobilisation in plants., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Based on peripheral blood lymphocyte subsets and common laboratory test indexes, this study aimed to construct a predictive scoring system for intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD)., Methods: Children hospitalized in Tianjin Children's Hospital from January 2021 to March 2023 were included in the study (185 cases of IVIG-sensitive KD and 41 cases of IVIG -resistant KD). Forty-six healthy children matched for age and gender were selected as controls. The relative percentage and absolute counts of peripheral lymphocyte subsets were measured by flow cytometry. Multivariate logistic regression was used to identify the predictive factors for IVIG-resistant KD and to construct a predictive scoring system for predicting IVIG-resistant KD., Results: The multivariate logistic regression analysis showed that CD4 + T cell absolute count, natural killer cell absolute count, serum sodium level, globulin level, and total bilirubin level were identified as predictive factors for IVIG-resistant KD ( P <0.05). The predictive scoring system based on these factors achieved a sensitivity of 70.7% and a specificity of 83.8% in predicting IVIG-resistant KD., Conclusions: Peripheral blood lymphocyte subsets can serve as predictive indicators for IVIG-resistant KD in children. The introduction of this indicator and the establishment of a scoring system based on it can provide a higher accuracy in predicting IVIG-resistant KD in children.

Background: Gestational diabetes mellitus (GDM) can lead to excessive pregnancy weight gain (PWG), abnormal glucolipid metabolism, and delayed lactation. Therefore, it is necessary to provide appropriate and effective interventions for pregnant women with GDM., Aim: To clarify the effects of individualized nutrition interventions on PWG, glucolipid metabolism, and lactation in pregnant women with GDM., Methods: The study population consisted of 410 pregnant women with GDM who received treatment at the Northern Jiangsu People's Hospital of Jiangsu Province and Yangzhou Maternal and Child Health Hospital between December 2020 and December 2022, including 200 who received routine in-terventions [control (Con) group] and 210 who received individualized nutrition interventions [research (Res) group]. Data on PWG, glucolipid metabolism [total cholesterol, (TC); triglycerides (TGs); fasting blood glucose (FPG); glycosylated hemoglobin (HbA1c)], lactation time, perinatal complications (cesarean section, premature rupture of membranes, postpartum hemorrhage, and pregnancy-induced hypertension), and neonatal adverse events (premature infants, fetal macrosomia, hypo-glycemia, and respiratory distress syndrome) were collected for comparative analysis., Results: The data revealed markedly lower PWG in the Res group vs the Con group, as well as markedly reduced TG, TC, FPG and HbA1c levels after the intervention that were lower than those in the Con group. In addition, obviously earlier lactation and statistically lower incidences of perinatal complications and neonatal adverse events were observed in the Res group., Conclusion: Individualized nutrition interventions can reduce PWG in pregnant women with GDM, improve their glucolipid metabolism, and promote early lactation, which deserves clinical promotion., Competing Interests: Conflict-of-interest statement: The authors declare no competing interests., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To explore the risk factors of malnutrition in infants with congenital heart disease within one year after surgery. Methods: This retrospective cohort study selected 502 infants with congenital heart disease who underwent surgical treatment in Guangzhou Women and Children's Medical Center from February 2018 to January 2019. Their basic information and clinical data were analyzed, and their nutrition status after the surgery was followed up by questionnaire survey. Weight-for-age Z score (WAZ)≤-2 one year after operation was defined as malnutrition group, and WAZ>-2 was non-malnutrition group. The perioperative indicators and complementary food advancement were compared between the two groups by chi-square test, t -test, and Kruskal-Wallis test. The risk factors of malnutrition were analyzed by Logistic regression. Results: A total of 502 infants were selected, including 301 males and 201 females, with the age of 4.1 (2.0, 6.8) months. There were 90 cases in malnutrition group and 412 cases in non-malnutrition group. The body length and weight at birth in the malnutrition group were lower than those in the non-malnutrition group ((47.8±3.8) vs. (49.3±2.5) cm, (2.7±0.6) vs. (3.0±0.5) kg, both P <0.001). The proportion of paternal high school education or above and the proportion of family per capita income of 5 000 yuan or above in the malnutrition group were lower than those in the non-malnutrition group ((18.9% (17/90) vs. 30.8% (127/412), 18.9% (17/90) vs. 33.7% (139/412), both P <0.05). Compared to the non-malnutrition group, the proportion of complex congenital heart disease in the malnutrition group was higher (62.2% (56/90) vs. 47.3% (195/412), P <0.05). The postoperative mechanical ventilation time, postoperative intensive care unit (ICU) stay time, postoperative hospital stay, total length of ICU stay and total hospital stay in the malnutrition group were significantly longer than those in non-malnutrition group (all P <0.05). The proportion of egg and fish supplementation over 2 times/week within one year after the surgery was also lower in the malnutrition group (both P <0.05). Logistic regression analysis showed that mother's weight at delivery ( OR =0.95,95% CI 0.91-0.99), the pre-operative WAZ≤-2 ( OR =6.04, 95% CI 3.13-11.65), the complexity of the cardiac disease ( OR =2.23, 95% CI 1.22-4.06), the hospital stay after the surgery over 14 days ( OR =2.61, 95% CI 1.30-5.26), the types of complementary food<4 ( OR =2.57, 95% CI 1.39-4.76), and the frequency of meat and fish<2 times/week ( OR =2.11, 95% CI 1.13-3.93) were the risk factors associated with malnutrition within one year after the surgery. Conclusion: Mother's weight at delivery pre-operative nutritional status, complexity of cardiac disease, postoperative hospital stay, types of daily supplements and frequency of fish are risk factors associated with malnutrition within one year after surgery in children with congenital heart disease.

Background: The incidence rate of acute pancreatitis (AP), which is a pathophysiological process with complex etiology, is increasing globally. miR-125b-5p, a bidirectional regulatory miRNA, is speculated to exhibit anti-tumor activity. However, exosome-derived miR-125b-5p in AP has not been reported., Aim: To elucidate the molecular mechanism of exosome-derived miR-125b-5p promoting AP exacerbation from the perspective of the interaction between immune cells and acinar cells., Methods: Exosomes derived from AR42J cells were isolated and extracted in active and inactive states by an exosome extraction kit, and were verified via transmission electron microscopy, nanoparticle tracking analysis, and western blotting. RNA sequencing assay technology was used to screen differentially expressed miRNAs in active and inactive AR42J cell lines, and bioinformatics analysis was used to predict downstream target genes of miR-125b-5p. The expression level of miR-125b-5p and insulin-like growth factor 2 (IGF2) in the activated AR42J cell line and AP pancreatic tissue were detected by quantitative real-time polymerase chain reaction and western blots. The changes in the pancreatic inflammatory response in a rat AP model were detected by histopathological methods. Western Blot was used to detect the expression of IGF2, PI3K/AKT signaling pathway proteins, and apoptosis and necrosis related proteins., Results: miR-125b-5p expression was upregulated in the activated AR42J cell line and AP pancreatic tissue, while that of IGF2 was downregulated. In vitro experiments confirmed that miR-125b-5p could promote the death of activated AR42J cells by inducing cell cycle arrest and apoptosis. In addition, miR-125b-5p was found to act on macrophages to promote M1 type polarization and inhibit M2 type polarization, resulting in a massive release of inflammatory factors and reactive oxygen species accumulation. Further research found that miR-125b-5p could inhibit the expression of IGF2 in the PI3K/AKT signaling pathway. Additionally, in vivo experiments revealed that miR-125b-5p can promote the progression of AP in a rat model., Conclusion: miR-125b-5p acts on IGF2 in the PI3K/AKT signaling pathway and promotes M1 type polarization and inhibits M2 type polarization of macrophage by inhibiting IGF2 expression, resulting in a large release of pro-inflammatory factors and an inflammatory cascade amplification effect, thus aggravating AP., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To analyze the follow-up and clinical effect of multidisciplinary treatment on the children with spinal muscular atrophy (SMA). Methods: The clinical data including nutritional status, respiratory function, bone health and motor function of 45 children with SMA who received multidisciplinary management 1-year follow-up in the Children's Hospital, Zhejiang University School of Medicine from July 2019 to October 2021 were retrospectively collected. Comparisons before and after management were performed using paired-samples t -test or Wilcoxon rank-sum test, etc. Results: The age of 45 patients (25 boys and 20 girls) was 50.4 (33.6, 84.0) months at the enrollment, with 6 cases of type 1, 22 cases of type 2, and 17 cases of type 3 respectively. After the multidisciplinary management, the cases of SMA patients with malnutrition decreased from 22 to 12 ( P =0.030), the level of vitamin D were significantly increased ((45±17) vs. (48±14) nmol/L, t =-4.13, P <0.001). There was no significant difference in the forced vital capacity %pred, the forced expiratory volume at 1 second %pred, and the peak expiratory flow %pred ((76±19)% and (76±21)%, (81±18)% and (79±18)%, (81±21)% and (78±17)%; t =-0.24, 1.36, 1.21; all P >0.05). The Cobbs angle of scoliosis also improved significantly (8.0°(0°, 13.0°) vs. 10.0°(0°, 18.5°), Z =-3.01, P =0.003). The Hammersmith functional motor scale expanded scores of children with SMA type 2 and type 3 both showed significant elevation (11.0 (8.0, 18.0) vs. 11.0 (5.0, 18.5) scores, 44.0 (36.5, 53.0) vs. 44.0 (34.0, 51.5) scores, Z =2.44, 3.11, P =0.015, 0.002). Conclusion: Multidisciplinary management is beneficial for delaying the progression of the multi-system impairments of SMA patients, such as malnutrition, restrictive ventilation dysfunction and scoliosis.

Objective: The purpose of this study was to evaluate the prognosis of patients with anomalous left coronary artery originating from pulmonary artery with varying cardiac function after surgical correction., Methods: This was a single-center retrospective cohort study including 51 patients with anomalous left coronary artery originating from pulmonary artery, all of whom underwent surgery at our center., Results: All 5 deaths occurred in the pre-operative low cardiac function group ( n = 39). After corrected by body surface area, parameters such as left coronary artery, right coronary artery, left atrial diameter, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, and main pulmonary artery diameter, were lower in patients in the normal cardiac function group than in the low cardiac function group. The rate of collateral circulation formation was higher in the normal cardiac function group. The proportion of changes of T wave was higher in the low cardiac function group ( P = 0.005), and the duration of vasoactive drugs (dopamine, milrinone, epinephrine, nitroglycerin.) was longer in the low cardiac function group. Left ventricular end-diastolic diameter, left ventricular end-systolic diameter, main pulmonary artery diameter, and left atrial diameter were smaller than those pre-operatively ( P < 0.05). Left ventricular ejection fraction was higher than that pre-operatively ( P = 0.003). The degree of mitral regurgitation in the low cardiac function group was reduced post-operatively ( P < 0.001)., Conclusion: There was a significant difference between the pre-operative baseline data of the low cardiac function group and the normal cardiac function group. After surgical repair, cardiac function gradually returned to normal in the low cardiac function group. The low cardiac function group required vasoactive drugs for a longer period of time. The left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left atrial diameter, and main pulmonary artery diameter decreased and gradually returned to normal after surgery. The degree of mitral regurgitation in the low cardiac function group was reduced after surgery., 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 Xia, Tao, Ma, Cui, Zou, Li, Li, Li, Zhang and Chen.)

Zeolite SAPO-34 has been widely used in the industry because of its special pore structure and wide distribution of acid sites in the pore channel. However, traditional SAPO-34 with a small pore size suffers from carbon deposition and deactivation in catalytic reactions, and its inability to catalytically convert bulky organic molecules limits its industrial application. Meanwhile, impurities of SAPO-5, which have weak acidity leading to rapid catalyst deactivation, appear in SAPO-34 zeolite. Therefore, it is of great significance to synthesize SAPO-34 zeolite with a mesoporous pore structure, which can significantly improve the transfer of molecules in zeolites. In this paper, SAPO-34 zeolite with a hierarchical pore structure was synthesized, and its hydrodesulfurization performance for 4,6-dimethyldibenzothiophene (4,6-DMDBT) was studied in a fixed bed reactor. The characteristic results show that BET-specific surface area, micropore volume, and mesoporous volume of synthesized SAPO-34 are 754 m 2  g -1 , 0.25, and 0.23 cm 3  g -1 respectively, and the pore size is mainly concentrated at 4 nm. The catalytic conversion of 4,6-DMDMT with Co- and Mo-supported SAPO-34 is about 83%, which is much higher than the catalytic performance of Al 2 O 3 ., 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 Wang, Cui, Ding, Xiang, Yu and Li.)

This study is aimed at exploring the potential role of GSDMC in kidney renal clear cell carcinoma (KIRC). We analyzed the expression of GSDMC in 33 types of cancers in TCGA database. The results showed that the expression of GSDMC was upregulated in most cancers. We found a significant association between high expression of GSDMC and shortened patient overall survival, progression-free survival, and disease-specific survival. In vitro experiments have shown that the expression of GSDMC was significantly elevated in KIRC cell lines. Moreover, decreased expression of GSDMC was significantly associated with decreased cell proliferation. In summary, we believe that this study provides valuable data supporting future clinical treatment., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021 Yun-Qian Cui et al.)

UCEC is one of the three common malignant tumors of the female reproductive tract. According to reports, the cure rate of early UCEC can reach 95%. Therefore, the development of prognostic markers will help UCEC patients to find the disease earlier and develop treatment earlier. The ALDH family was first discovered to be the essential gene of the ethanol metabolism pathway in the body. Recent studies have shown that ALDH can participate in the regulation of cancer. In our research, we explored the expression of the ALDH family in 33 cancers. It was found that ALDH2 was abnormally expressed in UCEC. Besides, in vivo and in vitro experiments were conducted to explore the effect of ALDH2 expression on the proliferation of UCEC cell lines. Meanwhile, the change of its expression is not due to gene mutations, but is regulated by miR-135-3p. At the same time, the impact of ALDH2 changes on the survival of UCEC patients is deeply discussed. Finally, a nomogram for predicting survival was constructed, with a C-index of 0.798 and AUC of 0.764. This study suggests that ALDH2 may play a crucial role in UCEC progression and has the potential as a prognostic biomarker of UCEC.

The potential effects of engineered nanoparticles (NPs) on metal bioaccumulation in aquatic organisms have been the focus of increasing research attention. However, while NPs typically aggregate, the role of aggregation in NP-mediated metal bioaccumulation is largely unknown. The present study investigated the effects of polyacrylate-coated TiO 2 (anatase) NPs (AnaNPs) on Cd bioaccumulation in zebrafish. The Ca concentration in the experimental medium was manipulated to regulate AnaNP aggregation. At the low Ca concentration, the AnaNPs were well-dispersed and there was little bioaccumulation. Under this condition, Cd bioaccumulation was mainly via the uptake of free ions (Route 1), with only a minor contribution from NP-Cd complexes (Route 2). Therefore, AnaNPs decreased Cd bioaccumulation, as their inductive carrier effect could not offset the inhibition induced by the decrease in the free Cd ion concentration as a result of NP adsorption. At the high Ca concentration, the AnaNPs aggregated and their bioaccumulation increased. Accordingly, Cd bioaccumulation was equally accounted for by Routes 1 and 2 but the overall amount of Cd remained unchanged because the inductive effect of the AnaNPs offset their inhibitory effect. Thus, during risk evaluations of NPs, the contribution of aggregation to metal bioaccumulation should be considered., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: The postoperative risk factors for electroencephalogram(EEG) abnormalities after paediatric cardiopulmonary bypass (CPB) remain to be identified. We investigated the characteristics of EEG abnormalities and risk factors in routine clinical management post-CPB., Methods: EEG and cerebral oxygen saturation (ScO2) were monitored in 96 patients (aged 3 days, 37 months, median 5 months) for 72 h post-CPB. Clinical measurements included 4-hourly arterial and central venous pressure, arterial blood gases, doses of inotropic and vasoactive drugs, daily C-reactive protein (CRP) and NT-proB-type Natriuretic Peptide (NT-proBNP). Demographics, STAT categories and outcomes (duration of mechanical ventilation,CICU stay) were recorded. Un., Results: Seizures occurred in 20 patients (20.8%) beginning at 0-48 hand lasting 10 min-31 h; background abnormalities occurred in 67 (69.8%) beginning at 0-8 h and lasting 4-48 h. Patients with EEG abnormalities had worse outcomes. In univariable regression, seizures positively correlated with STAT categories, CPB time, temperature, blood pressure, central venous pressure, NT-proBNP, CRP, lactate and epinephrine, negatively with ScO2 and PaCO2 (P < 0.001 for lactate and epinephrine, P < 0.1 for the remaining). The degree of background abnormalities positively correlated with STAT categories, CPB time, operative time, central venous pressure, milrinone, negatively with blood pressure (P = 0.0003-0.087); it negatively correlated with lower dose of epinephrine (P < 0.001) and positively with higher dose (P = 0.03l). In multivariable regression, seizures positively correlated with epinephrine, lactate and temperature; the background abnormality correlations remain significant except for milrinone and operative time (P < 0.001 for epinephrine, P < 0.05 for the remaining)., Conclusions: Numerous perioperative risk factors are associated with EEG abnormalities post-CPB. The most significant and consistent risk factor is epinephrine., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries (PA/VSD/MAPCAs) is complex and diverse that has led to a variety of treatment strategies. Experience has been largely obtained in the advanced countries. The clinical diversity is greater in China. We evaluated our surgical approaches and outcomes of these patients. Methods: We reviewed 127 patients undergoing varied surgeries in our center in 2010-2019. Results: Thirty patients underwent single-stage complete repair by unifocalizing MAPCAs and VSD closure (aged 3.9-131.4 months, median 22) with 3 (10%) early deaths. Ninety-seven underwent the first-stage rehabilitation strategy including systemic-to-pulmonary shunt in 29 (aged 0.5-144 month, median 8), and palliative RV-PA conduit in 68 (aged 2.2-209.6 months, median 14) with 5 (5.2%) early deaths. Eight-one patients (63.8%) eventually achieved complete repair with a median right/left ventricular (RV/LV) pressure ratio of 0.7 (ranged 0.4-1.0). Fourteen patients (11.0%) accepted palliation as final destination. Survival for the entire cohort was 89.5, 85.2, and 76.1% at 1, 5, and 10 years, respectively. Survival for those undergoing complete repair was 88.2 and 76.6% at 1 and 5 year, respectively. RV/LV pressure ratio ≥0.8 was risk factor for mortality (HR10.3, p = 0.003). Conclusions: Our cohort, the largest from China, had distinctive clinical features with substantially wider age range and higher RV/LV pressure ratio. Using the combined approaches tailored to individual patients, complete repair was achieved in 64% of patients. The early and intermediate outcomes are acceptable compared to many of the previous reports., 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 © 2021 Zou, Ma, Cui, Wang, Li, Li and Chen.)

Background: Nutrition therapies in children with congenital heart disease (CHD) after cardiopulmonary bypass (CPB) is crucial, but energy and protein requirements remain undefined. We assessed energy and protein requirements, with nitrogen kinetics and clinical outcomes, in infants with complex CHD following CPB., Methods: Infants were randomized to control (1.3 g/kg/d), moderate protein (MP, 2.5 g/kg/d), or high protein (HP, 4 g/kg/d) groups. Resting energy expenditure (REE) was measured 6 hours post-CPB and then at 24-hour intervals, using indirect calorimetry to formulate energy intakes. Enteral formula feeding was initiated 6 hours post-CPB and continued for 5 days. Nitrogen balance (NB); urea nitrogen waste and nitrogen retention; serum prealbumin level; and hepatic, renal, and cardiac function were measured daily. Mid-upper arm circumference and triceps skinfold were measured preoperatively and 5 days after CPB. Adverse outcomes (bacterial infection, reintubation, and cardiac intensive care unit (CICU) stay > 8 days) were recorded., Results: REE was not different across the 3 groups (P = .37). It declined from 62 ± 6 to 57 ± 7 kcal/kg/d over 5 days post-CPB (P = .02). NB and nitrogen retention became positive by day 3 in the HP group but remained negative in the other 2 groups (P = .045-.003), despite higher urea nitrogen waste in the HP group (P < .0001). The HP group had a greater increase in serum prealbumin level and anthropometric measures (P = .009-.03). Other measures were not significantly different across the 3 groups., Conclusions: In infants with complex CHD in the first 5 days post-CPB, protein and energy intakes of ≈4 g/kg/d and 60 kcal/kg/d, respectively, led to improved nutrition outcomes without increased adverse events., (© 2020 American Society for Parenteral and Enteral Nutrition.)

Chitosan/g-C 3 N 4 /TiO 2 (CS/CNT) nanofibers were fabricated by electrospinning technique for Cr(VI) removal through the adsorption and photocatalytic processes. The effects of crucial factors in the adsorption process including contact time (0-1440 min), pH (1-7), initial concentration of Cr(VI) (20-800 mg/L) were investigated. The photocatalytic experiment was executed in a photochemical reactor with an 800 W xenon lamp to simulate visible light. In adsorption process, at pH = 2, the adsorption capacities of chitosan (CS) nanofibers, CS/CNT 10:1 (CS : g-C 3 N 4 /TiO 2 = 10:1) nanofibers and CS/CNT 5:1 nanofibers were 20.8, 165.3 and 68.9 mg/g, respectively, suggesting the addition of g-C 3 N 4 /TiO 2 (CNT) could notably enhance the acid resistance of CS and widen its practical application. Under visible-light irradiation, the removal efficiency of Cr(VI) using CS/CNT nanofibers was appreciably improved, which was about 50 % higher than that of pure adsorption, indicating that the CS/CNT nanofibers exhibited the effective synergistic effect of adsorption and photocatalysis., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: Subbranches of Y-chromosome haplogroup C2a-L1373 are founding paternal lineages in northern Asia and Native American populations. Our objective was to investigate C2a-L1373 differentiation in northern Asia and its implications for Native American origins., Materials and Methods: Sequences of rare subbranches (n = 43) and ancient individuals (n = 37) of C2a-L1373 (including P39 and MPB373), were used to construct phylogenetic trees with age estimation by BEAST software., Results: C2a-L1373 expanded rapidly approximately 17.7,000-14.3,000 years ago (kya) after the last glacial maximum (LGM), generating numerous sublineages which became founding paternal lineages of modern northern Asian and Native American populations (C2a-P39 and C2a-MPB373). The divergence pattern supports possible initiation of differentiation in low latitude regions of northern Asia and northward diffusion after the LGM. There is a substantial gap between the divergence times of C2a-MPB373 (approximately 22.4 or 17.7 kya) and C2a-P39 (approximately 14.3 kya), indicating two possible migration waves., Discussion: We discussed the decreasing time interval of "Beringian standstill" (2.5 ky or smaller) and its reduced significance. We also discussed the multiple possibilities for the peopling of the Americas: the "Long-term Beringian standstill model," the "Short-term Beringian standstill model," and the "Multiple waves of migration model." Our results support the argument from ancient DNA analyses that the direct ancestor group of Native Americans is an admixture of "Ancient Northern Siberians" and Paleolithic communities from the Amur region, which appeared during the post-LGM era, rather than ancient populations in greater Beringia, or an adjacent region, before the LGM., (© 2020 Wiley Periodicals LLC.)

Introduction: Pulmonary embolism (PE) is a potentially fatal complication and its morbidity together with fatalness will further increase when in patients with malignant tumors. Fast and accurate early diagnosis of PE thus seems considerably important., Objective: To explore the risk factors of lung cancer complicated with PE., Materials and Methods: A retrospective cohort study consisted of 40 lung cancer patients with PE (PE group) and 60 lung cancer patients without PE (non-PE group) were analyzed., Results: The white blood cell (WBC) count, D-dimer and low-density lipoprotein (LDL) were higher in PE group than those in non-PE group (P < 0.05), whereas the arterial partial pressure of oxygen (PaO 2 ) in PE group was lower than that in non-PE group (P < 0.05). Carcinoembryonic antigen (CEA) level between two groups also exhibited statistical difference (P < 0.05). Those lung adenocarcinoma patients with stages III and IV tumor, coupled with deep venous thrombosis (DVT), having experienced bevacizumab treatment or platinum-based chemotherapy more likely suffered from PE (P < 0.05). The multivariate analysis revealed that high D-dimer, chemotherapy, DVT, stages III to IV, adenocarcinoma were independent risk factors associated with PE (P < 0.05). The overall survival time of patients in case group was significantly shorter than that in the control group with a median survival duration being 10.5 months (95%CI, 8.95-12.05) and 16.8 months (95%CI, 14.62-18.98), respectively, (P < 0.01)., Conclusions: High D-dimer, chemotherapy, DVT, stages III to IV and adenocarcinoma might have a positive correlation with PE, meanwhile, PE always predicted a poor prognosis in lung cancer patients., (© 2020 John Wiley & Sons Ltd.)

Background: There are conflicting results regarding whether corticosteroids have better efficacy than placebo in acute respiratory distress syndrome (ARDS) patients. Therefore, we aim to further evaluate the efficacy and safety of corticosteroids in adult ARDS patients., Methods: The databases, including Medline, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, were searched from their inception to May 2, 2020. Randomized controlled trials (RCTs) and observational cohort studies were selected to assess the use of corticosteroids in adult ARDS patients. The quality of the results was judged by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The inverse-variance method with random or fixed effects modeling was used to compute pooled odds ratio ( OR ), standardized mean difference ( SMD ), and their 95% confidence interval ( CI )., Results: Eight eligible RCTs and six cohort studies were included. The use of corticosteroids was associated with reduced mortality ( OR 0.57, 95% CI 0.43-0.76, I 2=35.1%, P =0.148) in ARDS patients, and the result was confirmed in the included cohort studies ( OR 0.51, 95% CI 0.27-0.95, I 2=66.7%, P =0.010). The subgroup analysis stratified by the initiation time and duration of corticosteroid use showed that early ARDS and prolonged corticosteroid use had significant survival benefits in the RCTs. The low-dose corticosteroid use was also associated with significantly more ventilator-free days and a reduced rate of new infections in ARDS patients., Conclusions: The low-dose corticosteroid therapy may be safe and reduce mortality, especially in patients with prolonged treatment and early ARDS., Competing Interests: Conflicts of interest: The authors have no conflicts of interest to disclose., (Copyright: © World Journal of Emergency Medicine.)

Nasal chondromesenchymal hamartoma (NCMH) is a rare destructive benign neoplasm that predominantly develops in infants and young children. The lesion is usually located in the nasal cavity, often in the adjacent paranasal sinuses and orbital region and especially in the ethmoid sinus. Because the imaging characteristics of NCMH often mimic the features of malignant tumors, it is clinically important to study the radiographic appearance of this disease. Therefore, we herein present the computed tomography and magnetic resonance imaging findings of NCMH occurring in a 7-year-old girl. The mass was resected via an endoscopic surgical approach and definitively diagnosed as NCMH based on histologic and immunohistochemical analysis. However, signs of tumor recurrence manifested 45 months after surgery. NCMH can be locally aggressive with an expansive and destructive radiographic appearance, which highly implies a malignant neoplasm. Hence, an accurate diagnosis is essential to avoid potentially harmful therapies, and detailed computed tomography or magnetic resonance imaging should be performed prior to surgery. Selective arterial embolization is also an important part of preoperative management because the degree of enhancement may not be adequate to determine the blood supply of the tumor. Moreover, complete radical excision cannot guarantee that the lesion will not recur.

Background: Pancreatic stellate cells (PSCs) activation plays a critical role in the development of chronic pancreatitis. Previous studies confirmed that thromboxane A2 receptor (TxA2r) was overexpressed in activated PSCs in rats. The purpose of this study was to investigate the role of TxA2r in the activation of PSCs induced by 8-epi-prostaglandin F2α (8-epi-PGF2α)., Methods: TxA2r expression in both quiescent and activated PSCs was detected by immunocytochemistry and immunoblot assay. Isolated PSCs were treated with 8-epi-PGF2α (10, 10, 10 mol/L) for 48 h, and SQ29548 (10, 10, and 10 mol/L), a TxA2r-specific antagonist for 48 h, respectively, to identify the drug concentration with the best biological effect and the least cytotoxicity. Then isolated PSCs were treated with SQ29548 (10 mol/L) for 2 h, followed by 10 mol/L 8-epi-PGF2α for 48 h. Real-time polymerase chain reaction was performed to detect the messenger RNA (mRNA) levels of α-smooth muscle actin (α-SMA) and collagen I. Comparisons between the groups were performed using Student's t test., Results: TxA2r was up-regulated in activated PSCs in vitro compared with quiescent PSCs (all P < 0.001). Compared with the control group, different concentrations of 8-epi-PGF2α significantly increased mRNA levels of α-SMA (10 mol/L: 2.23 ± 0.18 vs. 1.00 ± 0.07, t = 10.70, P < 0.001; 10 mol/L: 2.91 ± 0.29 vs. 1.01 ± 0.08, t = 10.83, P < 0.001; 10 mol/L, 1.67 ± 0.07 vs. 1.00 ± 0.08, t = 11.40, P < 0.001) and collagen I (10 mol/L: 2.68 ± 0.09 vs. 1.00 ± 0.07, t = 24.94, P < 0.001; 10 mol/L: 2.12 ± 0.29 vs. 1.01 ± 0.12, t = 6.08, P < 0.001; 10 mol/L: 1.46 ± 0.15 vs. 1.00 ± 0.05, t = 4.93, P = 0.008). However, different concentrations of SQ29548 all significantly reduced the expression of collagen I (10 mol/L: 0.55 ± 0.07 vs. 1.00 ± 0.07, t = 10.47, P < 0.001; 10 mol/L: 0.56 ± 0.10 vs. 1.00 ± 0.07, t = 6.185, P < 0.001; 10 mol/L: 0.27 ± 0.04 vs. 1.00 ± 0.07, t = 15.41, P < 0.001) and α-SMA (10 mol/L: 0.06 ± 0.01 vs. 1.00 ± 0.11, t = 15.17, P < 0.001; 10 mol/L: 0.28 ± 0.03 vs. 1.00 ± 0.11, t = 11.29, P < 0.001; 10 mol/L: 0.14 ± 0.04 vs. 1.00 ± 0.11, t = 12.86, P < 0.001). After being treated with SQ29548 (10 mol/L) and then 8-epi-PGF2α (10 mol/L), the mRNA levels of α-SMA (0.20 ± 0.08 vs. 1.00 ± 0.00, t = 17.46, P < 0.001) and collagen I (0.69 ± 0.13 vs. 1.00 ± 0.00, t = 4.20, P = 0.014) in PSCs were significantly lower than those of the control group., Conclusions: The results show that 8-epi-PGF2α promoted PSCs activation, while SQ29548 inhibited PSCs activation induced by 8-epi-PGF2α. The result indicated that TxA2r plays an important role during PSC activation and collagen synthesis induced by 8-epi-PGF2αin vitro. This receptor may provide a potential target for more effective antioxidant therapy for pancreatic fibrosis.

Objective: To set up a prediction scoring system for the hypoxemia in infants with Pierre Robin sequence after weaning and evaluate its clinical value. Methods: Data of consecutive patients from November 2016 to June 2019, who underwent mandibular distraction osteogenesis in Guangzhou Women and Children's Medical Center, were retrospectively analyzed ( n= 148). All the cases were divided into two groups according to the appearance of hypoxemia after weaning. They were randomly divided into the derivation cohorc (2/3, n= 100) and the validation cohort (1/3, n= 48). Single factor and multiple logistic regression analysis were used to select the independent risk factors related to hypoxemia and establish a prediction model. A prediction scoring system was developed in accordance with assigning of the value of each variable β in the model. Internal verification of scoring system by validation population. Data of consecutive patients from July 2019 to November 2019, who underwent mandibular distraction osteogenesis, were prospectively analyzed ( n= 26). The diagnostic accuracy were conducted to evaluate the clinical value of the scoring system. Results: The logistic regression demonstrated that age at operation, pulmonary infection and the length of distraction less than 5 mm at weaning were the independent risk factors for hypoxemia. The P value of logistic regression model in Hosmer and Lemeshow goodness of fit test was 0.848, and a prediction scoring system was established accordingly. The area under the ROC curve of the scoring system was 0.890, and the optimum critical value was 53. The sensitivity, specificity, accuracy of the model were 78.6%(11/14),86.1%(74/86), 85.0%(85/100) respectively. The predictive effectiveness of the scoring system in the retrospective validation population was similar to that in the modeling population. 26 patients were included in the prospective analysis. The area under ROC curve of the scoring system was 0.870. The sensitivity, specificity and accuracy were 80.0%(5/6),95.0%(20/21), 96.1%(25/26) respectively. Conclusion: The prediction scoring system established in the study are efficacious for the hypoxemia in infants with Pierre Robin sequence after weaning.

The widespread use of nanoparticles (NPs) has drawn considerable attention because of their potential toxicity and the environmental consequences thereof. However, the effects of the exposure route and life stage of an organism on the bioaccumulation and toxicity of NPs are largely unknown. In the present study, we investigated the accumulation kinetics (uptake, assimilation, and efflux) and tissue distribution of waterborne and dietary hematite NPs (HemNPs) during three life stages (embryo, larva, and adult) of the zebrafish Danio rerio. For all zebrafish life stages, the waterborne accumulation of well-dispersed HemNPs increased linearly with exposure time but decreased after reaching a maximum. The increase in HemNPs accumulation followed the order embryo > larva > adult. Compared with the waterborne route, the dietary accumulation of HemNPs in larval and adult zebrafish fluctuated, reaching a maximum after each food refreshment and then decreasing until the next food addition. Similar to waterborne exposure, adult fish accumulated less dietary HemNPs than did larvae. Nevertheless, dietary HemNPs mostly accumulated in the intestinal tract, with smaller amounts in the truncus, head, and gills, as compared with their waterborne counterparts. Moreover, in the gonad no dietary HemNPs were detected whereas accumulation via waterborne HemNPs was significant. Despite the low assimilation efficiency of dietary HemNPs, biodynamic modeling showed that the diet was the main source of particle accumulation in zebrafish. Thus, both the life stage and the exposure route should be considered in evaluations of the environmental risks of NPs., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

As the world faces water shortage and pollution crises, the development of novel visible light photocatalysts to purify water resources is urgently needed. Over the past decades, most of the reported photocatalysts have been in powder or granular forms, creating separation and recycling difficulties. To overcome these challenges, a flexible and recyclable heterostructured TiO 2 /polyvinylidene fluoride/graphitic carbon nitride (TiO 2 /PVDF/g-C 3 N 4 ) composite was developed by combining electrospinning, sintering and hydrothermal methods. In the composite, PVDF was used as a support template for removing and separating the photocatalyst from solution. Compared with pure TiO 2 , the TiO 2 /PVDF/g-C 3 N 4 composite exhibited the extended light capture range of TiO 2 into the visible light region. The photogenerated carriers were efficiently transferred and separated at the contact interface between TiO 2 and g-C 3 N 4 under visible light irradiation, which consequently increased the photocatalytic activity of the photocatalyst. In addition, the flexible composites exhibited excellent self-cleaning properties, and the dye on the photocatalysts was completely degraded by the as-prepared materials. Based on the intrinsic low cost, recyclability, absorption of visible light, facile synthesis, self-cleaning properties and good photocatalytic performances of the composite, the photocatalyst is expected to be used for water treatment.

Domestic Bactrian camel ( Camelus bactrianus ) used to be one of the most important livestock species in Chinese history, as well as the major transport carrier on the ancient Silk Road. However, archeological studies on Chinese C. bactrianus are still limited, and molecular biology research on this species is mainly focused on modern specimens. In this study, we retrieved the complete mitochondrial genome from a C. bactrianus specimen, which was excavated from northwestern China and dated at 1290-1180 cal. years before present (yBP). Phylogenetic analyses using 18 mitochondrial genomes indicated that the C. bactrianus clade was divided into two maternal lineages. The majority of samples originating from Iran to Japan and Mongolia belong to subclade A1, while our sample together with two Mongolian individuals formed the much smaller subclade A2. Furthermore, the divergence time of these two maternal lineages was estimated as 165 Kya (95% credibility interval 117-222 Kya), this might indicate that several different evolutionary lineages were incorporated into the domestic gene pool during the initial domestication process. Bayesian skyline plot (BSP) analysis suggest a slow increase in female effective population size of C. bactrianus from 5000 years ago, which corresponds to the beginning of domestication of C. bactrianus. The present study also revealed that there were extensive exchanges of genetic information among C. bactrianus populations in regions along the Silk Road.

Background: The intraflagellar transport protein 140 homolog (IFT140) is involved in the process of intraflagellar transport (IFT), a process that is essential for the formation and maintenance of most eukaryotic cilia and flagella. Variants IFT140 have been reported to account for ciliopathy but association with male fertility has never been described in humans. Here we report the identification of two novel variants of IFT140 which caused spermatogenic dysfunction and male infertility., Methods: Whole-exome sequencing was performed in a 27-year-old infertile man presented with severe oligozoospermia, asthenozoospermia, and teratozoospermia (OAT) without other physical abnormality. Sanger sequencing was used to verify gene variants in the patient, his healthy brother, and their parents. Morphology and protein expression in the patient's sperm were examined by transmission electron microscopy (TEM) and immunofluorescence staining. Function of gene variants was predicted by online databases., Results: Compound heterozygous variants of IFT140: exon16: c.1837G > A: p.Asp613Asn and exon31: c.4247G > A: p.Ser1416Asn were identified in the patient, both of which showed autosomal recessive inheritance in his family, and had extremely low allele frequency in the population. Morphological abnormalities of the head, nucleus, and tails and the absence of IFT140 from the neck and mid-piece of the patient's spermatozoa were observed. Mutation Taster database predicted a high probability of damage-causing by both variations., Conclusion: This study for the first time reported IFT140 variants that cause infertility in humans., (© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

CuS nanoflowers were loaded on anatase TiO 2 /polyvinylidene fluoride (PVDF) fibers by hydrothermal treated electrospun tetrabutyl orthotitanate (TBOT)/PVDF fibers at low temperature. The results indicated that the amount of copper source and sulfur source determined the crystallization and morphology of the resultant products. It was found that the composite of CuS narrowed the band gap energy of TiO 2 and enhanced the separation efficiency of the photogenerated electron-hole pairs of TiO 2 . The photocatalytic reaction rate of CuS/TiO 2 /PVDF fibers to rhodamine B was 3 times higher than that of TiO 2 /PVDF fibers under visible light irradiation. Besides, owing to the preparation process was carried out at low temperature, the flexibility of CuS/TiO 2 /PVDF fibers was ensured. In addition, the self-cleaning performance of the dye droplets on the resultant product surface was demonstrated under visible light. Meanwhile, the resultant product can automatically remove dust on the surface of the material under the rolling condition of droplets due to its hydrophobicity. Therefore, the as-prepared CuS/TiO 2 /PVDF fibers can not only degrade the contaminated compounds, but also depress the maintenance cost owing to its self-cleaning performance, which means a very practical application prospect.

Many studies have shown that (5R)-5-hydroxytriptolide is the optimal modified analogue of triptolide, possessing comparable immunosuppressive activity but much lower cytotoxicity than triptolide. Whether (5R)-5-hydroxytriptolide has preventive effects on neuroinflammation is unclear. This study was designed to pretreat primary astrocytes from the brains of neonatal Sprague-Dawley rats with 20, 100 and 500 nM (5R)-5-hydroxytriptolide for 1 hour before establishing an in vitro neuroinflammation model with 1.0 μg/mL lipopolysaccharide for 24 hours. The generation of nitric oxide was detected by Griess reagents. Astrocyte marker glial fibrillary acidic protein was measured by immunohistochemical staining. The levels of tumor necrosis factor-α and interleukin-1β in the culture supernatant were assayed by enzyme linked immunosorbent assay. Nuclear factor-κB/p65 expression was examined by immunofluorescence staining. The phosphorylation of inhibitor of nuclear factor IκB-α and the location of nuclear factor-κB/P65 were determined using western blot assay. Our data revealed that (5R)-5-hydroxytriptolide inhibited the generation of nitric oxide, tumor necrosis factor-α and interleukin-1β from primary astrocytes activated by lipopolysaccharide, decreased the positive reaction intensity of glial fibrillary acidic protein, reduced the expression of tumor necrosis factor alpha and interleukin-1β in culture supernatant, inhibited the phosphorylation of IκB-α and the translocation of nuclear factor-κB/P65 to the nucleus. These results have confirmed that (5R)-5-hydroxytriptolide inhibits lipopolysaccharide-induced glial inflammatory response and provides cytological experimental data for (5R)-5-hydroxytriptolide in the treatment of neurodegenerative diseases., Competing Interests: None

Using artificial water, the simultaneous partial nitrification, ANAMMOX (anaerobic ammonium oxidation), and denitrification (SNAD) granular sludge process was started in a sequencing batch reactor (SBR), and then the ammonia concentration in the influent was reduced gradually. After stable operation for a period of time under the low ammonia concentration, sewage treated by a pre-precipitation process was used as a substrate to investigate the performance and stability of the SNAD granular sludge process. The results show that after the SNAD process was successfully started, the ammonia removal rate was greater than 98%, and total the nitrogen removal rate was about 89%. As the influent ammonia concentration decreased, the nitride-oxidizing bacteria (NOB) activity was increased and the total nitrogen removal rate gradually decreased to 75%. When the pre-precipitated domestic sewage (NH 4 + -N 52-63 mg·L -1 , COD 99-123 mg·L -1 ) was used as the inflow, the average effluent removal rate of the total effluent was 73.2%, the effluent COD concentration was below 35 mg·L -1 , and the maximum effluent ammonia nitrogen and total nitrogen concentration were 0.7 mg·L -1 and 12.8 mg·L -1 . The ammonia and total nitrogen concentration in the continuous 30 day effluent reached the 1A level of the integrated discharge standard of water pollutants for municipal wastewater treatment, indicating that the removal of organics and nitrogen from domestic sewage was achieved efficiently and synchronously.

To study the effect of the startup strategies on the simultaneous partial nitrification, ANAMMOX, and denitrification (SNAD) granular sludge processes, these processes were initiated by starting the completely autotrophic nitrogen removal over nitrite (CANON) process and anaerobic ammonia oxidation-denitrification (SAD) process at 12.7℃ and 18.3℃, respectively. The results show that the ammonia nitrogen was almost completely removed and the total nitrogen removal rate reached 86.7% after the R1 reactor was successfully started. When the ammonia concentration was low, the total nitrogen removal rate in the effluent decreased to 75.3%, the total nitrogen concentration in the effluent was~10 mg·L -1 , and excessive proliferation of the NOB was observed. The total nitrogen concentration in the effluent exceeded the 1A level of the integrated discharge standard of water pollutants applied in Beijing City. After the R2 reactor was successfully started, the effluent contained almost no ammonia nitrogen and the total nitrogen removal rate was~89.1%, that is, slightly higher than that of the R1 reactor. When the ammonia concentration was low, the concentration of ammonia nitrogen in effluent was less than 1.0 mg·L -1 and the total nitrogen concentration in the effluent was less than 6 mg·L -1 . The concentrations of ammonia nitrogen and total nitrogen in the effluent reached the 1A level of the integrated discharge standard of water pollutants applied in Beijing City. First, the startup of the SAD process gradually eliminated the NOB from the system through anaerobic operation in the initial stage of the startup, maintained the stability of the system, provided a good basis for the subsequent aeration to start the SNAD process, maintained the stable operation of the reactor, and the long-term discharge of total nitrogen reached the standard.

Objective:   To investigate the influences of long non-coding ribonucleic acid (lncRNA) small nucleolar RNA host gene 20 (SNHG20) on proliferation and apoptosis of glioma cells, and further explore the mechanism of SNHG20 in the incidence and development of glioma., Patients and Methods: A total of 80 cases of glioma specimens and 80 cases of para-carcinoma specimens were collected, and the expression level of SNHG20 was detected via reverse transcription-polymerase chain reaction (RT-PCR). The human glioma U118 and U251 cell lines with the stable knockout of SNHG20 were constructed using the small-interfering RNA (siRNA). The influence of SNHG20 on proliferation of human glioma cells was detected via cell counting kit-8 (CCK-8), and the protein expression levels of apoptosis-related genes, B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax), were also detected. The apoptosis level of glioma cells was detected in blank control group and SNHG20 siRNA group using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) technique. At the same time, the expression levels of proteins related to the phosphatase and tensin homolog deleted on chromosome ten/phosphatidylinositol 3-hydroxy kinase/protein kinase B (PTEN/PI3K/AKT) signaling pathway were detected via Western blotting., Results: The expression level of SNHG20 messenger RNA (mRNA) in glioma tissues was significantly higher than that in para-carcinoma tissues (p<0.05). After the inhibition of siRNA on SNHG20, the proliferation of U118 and U251 cells was significantly inhibited, and the expression of Bax was significantly up-regulated, while that of Bcl-2 was down-regulated. The TUNEL results showed that the number of apoptotic cells in SNHG20 siRNA group was about 12 times that in control group (p<0.05). After SNHG20 knockout, the protein expressions in the PTEN/PI3K/AKT signaling pathway were inhibited (p<0.05)., Conclusions: Inhibiting the SNHG20 expression in glioma cells can increase the apoptosis of glioma cells, and the mechanism may be related to the SNHG20-mediated PTEN/PI3K/AKT signaling pathway.

Congenital heart disease (CHD) is 1 of the most common congenital malformations, and considerable numbers of infants and young children with CHD undergo cardiopulmonary bypass surgery. It has been increasingly realized that perioperative nutrition support plays an important role in improving clinical outcomes. The purpose of this review, by searching PubMed, was to examine the nutrition conditions in perioperative children with CHD and the main problems in nutrition management in the cardiac intensive care unit (CICU), based on which future directions were proposed. We found that preoperative poor nutrition status is common. This limited reserve of energy and protein is further compounded by the complex metabolic alterations with hypermetabolism, hypercatabolism, and hypoanabolism in the early postoperative course. Knowledge about energy and protein metabolism and requirements in children after cardiopulmonary bypass remains very limited. The current nutrition recommendations in the CICU are based on little evidence. Insufficient energy and protein supply to meet demands remains a norm in the immediate postoperative period. The commonly used predictive equations do not provide accurate estimate of energy requirement in individual patients during the highly dynamic postoperative course. Indirect calorimetry can provide the best estimate of energy requirements for children with CHD in the CICU. Measurement of nitrogen balance is the recommended method to determine the minimal protein requirement. During the early postoperative period, daily measurements of resting energy expenditure using indirect calorimetry and nitrogen balance in each individual child are essential to optimize energy and protein supply to meet requirements., (© 2018 American Society for Parenteral and Enteral Nutrition.)

We carried out density functional theory simulations to examine the stability and CO oxidation activity of single Cu atoms supported on CeO 2 (111). Both the strong binding energy and high activation energy for Cu single atom diffusion indicate a high stability of the Cu 1 /CeO 2 single-atom catalyst. Electronic structure analysis verifies the formation of Cu + cation due to electron transfer. The frequency analysis further corroborates that the experimentally observed IR bands around 2114-2130 cm -1 of CO adsorption at the boundary of Cu/CeO 2 correspond to Cu + -carbonyl species. Cu 1 /CeO 2 single-atom catalyst displays a promising catalytic activity for CO oxidation via Mars van Krevelen mechanism., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To survey the conduction and evaluate the effectiveness of extracorporeal membrane oxygenation (ECMO) therapy in pediatric intensive care unit (PICU) in China mainland. Methods: In a questionnaire-based survey, we retrospectively reviewed the application of ECMO in children's hospital and general hospital in China mainland to summarize and analyze the categories of diseases and prognosis of children treated with ECMO therapy. Results: By December 31, 2017, a total of 23 hospitals using ECMO, including 22 tertiary referral hospitals and 1 secondary hospital, among which 16 were children's hospitals and 7 were general hospitals. Thirty-seven ECMO equipment was available. A total of 518 patients treated with ECMO, within whom 323 (62.4%) successfully weaned from ECMO and 262 (50.6%) survived to discharge. Among 375 pediatric patients, 233 (62.1%) were successfully weaned from ECMO and 186 (49.6%) survived to discharge. Among 143 newborn patients, 90 (62.9%) successfully weaned from ECMO, 76 (53.1%) survived to discharge. ECMO was applied in veno-arterial (VA) mode to 501 (96.7%) patients, veno-venous (VV) mode to 14 (2.7%) patients, and VV-VA conversion mode to 3 (0.6%) patients. Sixty-nine patients required extracorporeal cardiopulmonary resuscitation (ECPR), including 20 newborn patients (29.0%) and 38 pediatric patients (71.0%), who were all with cardiovascular disease. Neonatal respiratory distress syndrome (26/61), persistent pulmonary hypertension of the newborn (PPHN) (12/61), and meconium aspiration syndrome (MAS) (11/61) are the most common pulmonary diseases in newborn patients; among whom, infants with PPHN had highest survival rate (10/12), followed by MAS (9/11). Among newborn patients with cardiovascular diseases, those who admitted were after surgery for congenital cardiac disease were the most common (54/82), while those with septic shock had the highest survival rate (2/3). In pediatric pulmonary diseases, acute respiratory distress syndrome was the most common (42/93), while plastic bronchitis was with the highest survival rate (4/4), followed by viral pneumonia (13/16). Among pediatric cardiovascular diseases, congenital cardiac defect was the most common (124/282), while fulminant myocarditis had the highest survival rate (54/77). Conclusion: The application of ECMO as a rescue therapy for children with severe cardiopulmonary failure has dramatically developed in China mainland.

Outside the municipal waste water treatment plant(WWTP) which located in Mentougou District, Beijing, the effluent of the anoxic/oxic(A/O) phosphorus removal process served as the substrate to operate a completely autotrophic nitrogen removal over nitrite(CANON) filter reactor.. After the reactor was successfully activated, glucose was added to the influent as the organic carbon source. The simultaneous partial nitrification, anaerobic ammonium oxidation (ANAMMOX), and denitrification (SNAD) process was started to study the effect of SNAD filter on sewage treatment. The results showed that from 119 d to 128 d, the ammonia removal rate of the CANON process was more than 95%, and the maximum total nitrogen concentration in the effluent was 13.0 mg·L -1 . Total nitrogen concentration surpassed the 1A level of the Integrated Discharge Standard of Water Pollutants applied in Beijing City. The SNAD process was started by adding glucose to the influent at 129 d. The total nitrogen removal rate of this process was about 85% at 133-187 d, and the total nitrogen concentration in the effluent was 5.5-7.3 mg·L -1 . The filter plugged up at 195 d, and backwash was utilized at 196 d. During the subsequent 30 d, the total nitrogen removal rate of the reactor was greater than 85%, and the total nitrogen concentration in the effluent remained at 6.2-7.2 mg·L -1 . Compared with the CANON process, the SNAD process improved the total nitrogen removal rate and reduced the total nitrogen concentration of the effluent by 6 mg·L -1 . The ammonia and total nitrogen concentrations in effluent satisfied the 1A level of the Integrated Discharge Standard of Water Pollutants.

Objective: To evalute the clinical outcomes of intracytoplasmic sperm injection(ICSI) for infertility male with severe asthenospermia induced by multiple morphological anomalies of the flagella (MMAF). Methods: The clinical data of 15 patient with MMAF were retrospectively analyzed, who underwent ICSI treatment using hyponotic swelling test the "live" sperm in the Department of Reproductive Medicine of Yantai Yuhuangding Hospital from January 2011 to December 2016. Another 30 obstructive azoospermia (OA)patients are matched strictly who also accepted ICSI in the same treatment time. The two groups were compared in the couples'age, the body mass index(BMI), the duration of infertility, the retrieved oocytes, the number of ICSI oocytes, and the rates of fertilization, cleavage, transferrable embryos, good embryos, embryos implanted, clinical pregncncy, early abortion, singleton and twins. Results: After 27 cycles of ICSI, all of the MMAF patients achieved clinical pregnancy, including 11 cases of live birth, 2 cases of spontaneous abortion, and 2 cases of pregnancy maintenance. There were no significant difference between MMAF and OA groups in the couples'age and BMI, or the numbers of retrieved oocytes and ICSI oocytes( P >0.05), but the differences in the infertility duration had statistical meaning( P <0.001). No statistical differences were observed among groups in ICSI fertility rate(92.0% vs 91.6%), clesvage rate(95.4% vs 96.5%), high-quality embryonic rate(56.5% vs 57.5%), good blastocyst rate(23/61 vs 35/94), embryo implantation rate(20/48 vs 35/75), early abortion rate(4/19 vs 8/36), clinical pregncncy rate(15/27 vs 28/50), singleton rate (10/13 vs 20/25)and twinning rate(3/13 vs 5/25)( P >0.05). Conclusions: MMAF may not affect ICSI treatment outcomes, but genetic defects can be transmitted through ICSI. The affected couples should be informed of the necessity of prenatal genetic diagnosis before embryo implantation and the inevitable vertical transmission of genetic problems to the offspring.

The aim of the present study was to investigate the protective effect of granulocyte colony-stimulating factor (G-CSF) on acute ischemic cerebral injury, and its mechanism through the impact of G-CSF on early growth response-1 (Egr-1) and vascular endothelial growth factor (VEGF) expressions. Male Sprague-Dawley (SD) rats were divided them into three groups, i.e., the sham, model and G-CSF groups to measure the effect of G-CSF on the volume of cerebral infarction and level of lactate dehydrogenase (LDH) in rats. Hematoxylin and eosin (H&E) staining method was performed for histopathological examination. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis were used to detect the mRNA and protein expressions of Egr-1 and VEGF in different groups. Furthermore, Statistical Product and Service Solutions (SPSS) 17.0 software was applied to detect the differences in the expression of Egr-1 and VEGF between the two groups. Compared with the sham group, we found that the volume of cerebral infarction and LDH content in the model group were significantly elevated. By contrast, in the model group, those indicators in the G-CSF group were obviously decreased. H&E staining results also showed that G-CSF could decrease the necrotic area in cerebral infarction and the incidence of inflammation, and sustain the integrity of the molecular structure. Immunofluorescence staining results revealed that the protein expressions of Egr-1 and VEGF in the model group were all significantly decreased, while those in the G-CSF group were remarkably elevated. RT-PCR and western blot analysis revealed that the mRNA and protein expressions of Egr-1 and VEGF in the model group were decreased obviously, but those in the G-CSF group were elevated significantly, and the differences between the two groups showed statistical significance (P<0.05). G-CSF manifests a significant protective effect on the acute ischemic cerebral injury, which may be realized through its effect on the expressions of Egr-1 and VEGF.

Oligoasthenoteratozoospermia (OAT) is characterized as low sperm count, decreased sperm motility and structural abnormalities of the sperm head in the same patient. However, very few studies reported the genetic alterations associated with OAT. Here we report a 38-year-old patient with OAT from a consanguineous family, with 2-6 million/mL sperm density, 2.1-3.8% normal sperm morphology and immotile sperm. Whole-exome sequencing (WES) identified homozygous variant c.1259A>G:p.Y420C in the TDRD6 gene. TDRD6 is a testis-specific expressed protein that was localized to the chromatoid bodies in germ cells and played an important role in the nonsense-mediated decay pathway. This rare variant co-segregated with the OAT phenotype in this family. Bioinformatic analysis also suggested the variant a pathogenic mutation. Two intracytoplasmic sperm injection (ICSI) cycles were carried out in the patient's wife, but she did not become pregnant after embryo transfer. So the mutations in TDRD6 may be associated with human male infertility and early embryonic lethality., (Copyright © 2018. Published by Elsevier B.V.)

Britannin (Bri), isolated from Inula aucheriana, is a sesquiterpene lactone (SL), a class of secondary metabolites. Previous studies have suggested the anti-cancer potential of Bri; however, the molecular mechanism remains elusive. The present study investigated the effects of Bri on liver cancer progression. Our findings indicated that Bri significantly suppressed the growth of liver cancer cell lines. Mechanistic researches revealed that Bri induced apoptosis through the extrinsic and intrinsic apoptotic pathways, as evidenced by the increase of Caspase-8, -9 and -3 cleavages. In addition, Bri-triggered autophagy in liver cancer cells, supported by the up-regulation of light chain 3 (LC3) II, p62, autophagy-related 5 (ATG5) and Beclin 1, as well as the occurrence of autophagic vacuoles. Importantly, Bri increased AMPK activation, while decreased the activity of its down-streaming signal, mTOR. Of note, suppression of AMP-activated protein kinase (AMPK) activation using its inhibitor, Compound C, could inhibit both apoptosis and autophagy induced by Bri. Furthermore, Bri was found to induce reactive oxygen species (ROS) generation in hepatic cancer cells. Notably, reducing ROS production by its scavenger, N-acetyl cysteine (NAC), could down-regulate p-AMPK levels, while up-regulate the phosphorylated mechanistic target of rapamycin (p-mTOR) expressions, accompanied with the restored cell viability, as well as the reduced apoptosis and autophagy in Bri-treated liver cancer cells. Finally, Bri inhibited the tumor growth in vivo without side effects. In conclusion, our study illustrated that Bri could induce apoptosis and autophagy by activating AMPK regulated by ROS in liver cancer cells, supplying molecular bases for developing Bri into an effective candidate against liver cancer., (Copyright © 2017. Published by Elsevier Inc.)