An indel introduced by Neanderthal introgression, rs3835124:ATTTATT > ATT, might contribute to prostate cancer risk by regulating PDK1 expression.

INTRODUCTION: Prostate cancer is one of the most common cancer types in males and rs12621278:A > G has been suggested to be associated with this disease by previous genome-wide association studies. One thousand genomes project data analysis indicated that rs12621278:A > G is within two long-core haplotypes. However, the origin, causal variant(s), and molecular function of these haplotypes were remaining unclear. MATERIALS AND METHODS: Population genetics analysis and functional genomics work was performed for this locus. RESULTS: Phylogeny analysis verified that the rare haplotype is derived from Neanderthal introgression. Genome annotation suggested that three genetic variants in the core haplotypes, rs116108611:G > A, rs139972066:AAAAAAAA > AAAAAAAAA, and rs3835124:ATTTATT > ATT, are located in functional regions. Luciferase assay indicated that rs139972066:AAAAAAAA > AAAAAAAAA and rs116108611:G > A are not able to alter ITGA6 (integrin alpha 6) and ITGA6 antisense RNA 1 expression, respectively. In contrast, rs3835124:ATTTATT > ATT can significantly influence PDK1 (pyruvate dehydrogenase kinase 1) expression, which was verified by expression quantitative trait locus analysis. This genetic variant can alter transcription factor cut like homeobox 1 interaction efficiency. The introgressed haplotype was observed to be subject to positive selection in East Asian populations. The molecular function of the haplotype suggested that Neanderthal should be with lower PDK1 expression and further different energy homeostasis from modern human. CONCLUSION: This study provided new insight into the contribution of Neanderthal introgression to human phenotypes.

Meroterpenoids from Marine Sponge Hyrtios sp. and Their Anticancer Activity against Human Colorectal Cancer Cells.

Two new meroterpenoids, hyrtamide A (1) and hyrfarnediol A (2), along with two known ones, 3-farnesyl-4-hydroxybenzoic acid methyl ester (3) and dictyoceratin C (4), were isolated from a South China Sea sponge Hyrtios sp. Their structures were elucidated by NMR and MS data. Compounds 2-4 exhibited weak cytotoxicity against human colorectal cancer cells (HCT-116), showing IC50 values of 41.6, 45.0, and 37.3 µM, respectively. Furthermore, compounds 3 and 4 significantly suppressed the invasion of HCT-116 cells while also downregulating the expression of vascular endothelial growth factor receptor 1 (VEGFR-1) and vimentin proteins, which are key markers associated with angiogenesis and epithelial-mesenchymal transition (EMT). Our findings suggest that compounds 3 and 4 may exert their anti-invasive effects on tumor cells by inhibiting the expression of VEGFR-1 and impeding the process of EMT.

Effect of CPB glucose levels on inflammatory response after pediatric cardiac surgery.

BACKGROUND: Systemic inflammatory response syndrome (SIRS) is a common complication after cardiac surgery. There are no definite optimal glycemic threshold for pediatric patients receiving open-heart surgery with CPB. The study aimed to investigate the optimal cardiopulmonary bypass (CPB) glucose in patients undergoing cardiac surgery. METHODS: We enrolled children with congenital heart disease who underwent surgical repair between June 2012 and December 2020. We included only patients who underwent cardiac surgery with CPB. The primary outcome was severe SIRS. A two-piece-wise regression model was applied to examine threshold effect of CPB glucose on severe SIRS. RESULTS: A total of 7350 patients were enrolled in the present study, of whom 3895 (52.99%) are female. After potential confounders were adjusted, non-linear relationship was detected between CPB glucose and severe SIRS, whose turning point was 8.1. With CPB glucose < 8.1 mmol/L, the estimated dose-response curve was consistent with a horizontal line. However, the prevalence of severe SIRS increased with increasing glucose up to the turning point (Glucose > 8.1 mmol/L); the odds ratio (OR) of the Glucose was 1.35 (95% CI 1.21, 1.50). CONCLUSIONS: The present study indicates the association of CPB glucose with inflammatory response after pediatric cardiac surgery. The patients might have the best outcomes with the optimal CPB glucose no more than 8.1 mmol/L.

Association of LDL to HDL ratio with new-onset atrial fibrillation after on-pump coronary artery bypass graft surgery.

OBJECTIVE: This study aims to analyze the association between preoperative LDL/HDL ratio and new-onset atrial fibrillation (AF) after on-pump coronary artery bypass grafting (on-pump CABG), evaluate the clinic value of preoperative LDL/HDL ratio to identify postoperative rhythm. METHODS: A retrospective study of consecutive patients (n = 2052) who underwent on-pump CABG at TEDA International Cardiovascular Hospital (Tianjin, China), from June 1, 2020, to December 30, 2021, was conducted. The association between preoperative LDL/HDL and new-onset POAF was analyzed by Lowess curve and univariate logistic regression. The receiver operating characteristic curve (ROC) and area under the curve (AUC) were used to evaluate the identification capacity of preoperative LDL/HDL level for new-onset POAF. RESULTS: In studied populations, the incidence of new-onset POAF was about 29.24%. The lowess curve showed that the association between preoperative LDL/HDL ratio and POAF after on-pump CABG was similar to a linear relationship. With the increasement of preoperative LDL/HDL ratio, the incidence of POAF increased simultaneously. ROC analysis showed that preoperative LDL/HDL ratio could identify postoperative arrhythmia after on-pump CABG (AUC = 0.569,95% CI = 0.529-0.608, P = 0.006) among female patients, the best preoperative LDL/HDL ratio cutoff of 2.11, which was considered a predictive factor of incident POAF, showed a sensitivity of 83.60% (95% CI = 0.775-0.886) and a specificity of 30.02% (95% CI = 0.257-0.346). CONCLUSION: Preoperative LDL/HDL ratio is associated with new-onset POAF, but there is a difference in different sex. Preoperative LDL/HDL level can help to identify postoperative rhythm in females.

Factors influencing the functional status of aortic valve in ovine models supported by continuous-flow left ventricular assist device.

OBJECTIVES: An acute animal experiment was performed to observe factors influencing the functional status of the aortic valve functional status after continuous-flow left ventricular assist device (CF-LVAD) implantation in an ovine model, and a physiologic predictive model was established. METHODS: A CF-LVAD model was established in Small Tail Han sheep. The initial heart rate (HR) was set to 60 beats/min, and grouping was performed at an interval of 20 beats/min. In all groups, the pump speed was started from 2000 rpm and was gradually increased by 50-100 rpm. A multi-channel physiological recorder recorded the HR, aortic pressure, central venous pressure, and left ventricular systolic pressure (LVSP). A double-channel ultrasonic flowmeter was used to obtain real-time artificial vascular blood flow (ABF). A color Doppler ultrasound device was applied to assess the aortic valve functional status. Multivariate dichotomous logistic regression was used to screen significant variables for predicting the functional status of the aortic valve. RESULTS: Observational studies showed that ABF and the risk of aortic valve closure (AVC) were positively correlated with pump speed at the same HR. Meanwhile, the mean arterial pressure (MAP) was unaltered or slightly increased with increased pump speed. When the pump speed was constant, an increase in HR was associated with a decrease in the size of the aortic valve opening. This phenomenon was accompanied by an initial transient increase in the ABF and MAP, which subsequently decreased. Statistical analysis showed that the AVC was associated with increased pump speed (OR = 1.02, 95% CI = 1.01-1.04, p = 0.001), decreased LVSP (OR = 0.95, 95% CI = 0.91-0.98, p = 0.003), and decreased pulse pressure (OR = 0.82, 95% CI = 0.68-0.96, p = 0.026). ABF or MAP was negatively associated with the risk of AVC (OR < 1). The prediction model of AVC after CF-LVAD implantation exhibited good differentiation (AUC = 0.973, 95% CI = 0.978-0.995) and calibration performance (Hosmer-Lemeshow χ2  = 9.834, p = 0.277 > 0.05). CONCLUSIONS: The pump speed, LVSP, ABF, MAP, and pulse pressure are significant predictors of the risk of AVC. Predictive models built from these predictors yielded good performance in differentiating aortic valve opening and closure after CF-LVAD implantation.

Differential expression of the Hsf family in cassava under biotic and abiotic stresses.

Heat shock transcription factors (Hsfs) are important regulators of biotic and abiotic stress responses in plants. Currently, the Hsf gene family is not well understood in cassava, an important tropical crop. In the present study, 32 MeHsf genes were identified from the cassava genome database, which were divided into three types based on functional domain and motif distribution analyses. Analysis of the differential expression of the genes belonging to the Hsf family in cassava was carried out based on published cassava transcriptome data from tissues/organs (leaf blade, leaf midvein, lateral buds, organized embryogenic structures, friable embryogenic callus, fibrous roots, storage roots, stem, petiole, shoot apical meristem, and root apical meristem) under abiotic stress (cold, drought) or biotic stress (mealybugs. cassava brown streak disease, cassava bacterial blight). The results show the expression diversity of cassava Hsfs genes in various tissues/organs. The transcript levels of MeHsfB3a, MeHsfA6a, MeHsfA2a, and MeHsfA9b were upregulated by abiotic and biotic stresses, such as cold, drought, cassava bacterial blight, cassava brown streak disease, and mealybugs, indicating their potential roles in mediating the response of cassava plants to environment stresses. Further interaction network and co-expression analyses suggests that Hsf genes may interact with Hsp70 family members to resist environmental stresses in cassava. These results provide valuable information for future studies of the functional characterization of the MeHsf gene family.

Apple ring rot-responsive putative microRNAs revealed by high-throughput sequencing in Malus × domestica Borkh.

MicroRNAs (miRNAs) are small non-coding RNAs, which silence target mRNA via cleavage or translational inhibition to function in regulating gene expression. MiRNAs act as important regulators of plant development and stress response. For understanding the role of miRNAs responsive to apple ring rot stress, we identified disease-responsive miRNAs using high-throughput sequencing in Malus × domestica Borkh.. Four small RNA libraries were constructed from two control strains in M. domestica, crabapple (CKHu) and Fuji Naga-fu No. 6 (CKFu), and two disease stress strains, crabapple (DSHu) and Fuji Naga-fu No. 6 (DSFu). A total of 59 miRNA families were identified and five miRNAs might be responsive to apple ring rot infection and validated via qRT-PCR. Furthermore, we predicted 76 target genes which were regulated by conserved miRNAs potentially. Our study demonstrated that miRNAs was responsive to apple ring rot infection and may have important implications on apple disease resistance.

rs2736098, a synonymous polymorphism, is associated with carcinogenesis and cell count in multiple tissue types by regulating TERT expression.

rs2736098 is a synonymous polymorphism in TERT (telomerase reverse transcriptase), an enzyme involved in tumor onset of multiple tissues, and should play no roles in carcinogenesis. However, a search in cancer somatic mutation database indicated that the mutation frequency at rs2736098 is much higher than the average one for TERT. Moreover, there are significant H3K4me1 and H3K27Ac signals, two universal histone modifications for active enhancers, surrounding rs2736098. Therefore, we hypothesized that rs2736098 might be within an enhancer region, regulate TERT expression and influence cancer risk. Through luciferase assay, it was verified that the enhancer activity of rs2736098C allele is significantly higher than that of T in multiple tissues. Transfection of plasmids containing TERT coding region with two different alleles indicated that rs2736098C allele can induce a significantly higher TERT expression than T. By chromatin immunoprecipitation, it was observed that the fragment spanning rs2736098 can interact with USF1 (upstream transcription factor 1). The two alleles of rs2736098 present evidently different binding affinity with nuclear proteins. Database and literature search indicated that rs2736098 is significantly associated with carcinogenesis in multiple tissues and count of multiple cell types. All these facts indicated that rs2736098 is also an oncogenic polymorphism and plays important role in cell proliferation.

Comparison of in-hospital outcomes after coronary artery bypass graft surgery in elders and younger patients: a multicenter retrospective study.

OBJECTIVES: We aimed to identify in-hospital outcomes in young (≤ 65 years) and old (> 65 years) patients after coronary artery bypass grafting (CABG) by analyzing the effect of age on adverse events after on-pump or off-pump CABG. METHODS: Patients older than 65 years were defined as older patients and others were defined as younger patients. The qualitative data were compared by chi-square or Fisher's exact tests. The quantitative data were compared by the two-sample independent t-test or Mann-Whitney U test. Multifactor binary logistic regression was used to control for confounders and to investigate the effect of age on dichotomous outcome variables such as death. RESULTS: In the on-pump CABG population, the postoperative in-hospital mortality, the incidence of postoperative symptomatic cerebral infarction (POSCI) and postoperative atrial fibrillation (POAF) was higher in older patients than in younger patients (P value < 0.05), and age > 65 years was associated with postoperative in-hospital mortality (OR = 2.370, P value = 0.031), POSCI (OR = 5.033, P value = 0.013), and POAF (OR = 1.499, P value < 0.001). In the off-pump CABG population, the incidence of POAF was higher in older patients than in younger patients (P value < 0.05), and age > 65 years was associated with POAF (OR = 1.392, P value = 0.011). CONCLUSION: In-hospital outcomes after CABG are strongly influenced by age. In on-pump CABG, the risk of postoperative death, POSCI, and POAF was higher in older patients, and in off-pump CABG, the risk of POAF was higher in older patients.

A prediction model for new-onset atrial fibrillation following coronary artery bypass graft surgery: A multicenter retrospective study.

Objective: Developing and assessing a risk prediction model of postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG), and aims to provide a reference for the prediction and prevention. Design: A retrospective case-control study. Setting: Three major urban teaching and university hospitals and tertiary referral centers. Participants: consecutive patients undergoing CABG. Interventions: The study was retrospective and no interventions were administered to patients. Measurements and main results: In the study, the overall new-onset POAF prevalence was approximately 28%. A prediction model for POAF with nine significant indicators was developed, and identified new predictors of POAF: left ventricular end diastolic diameter (LVEDD), intraoperative defibrillation, and intraoperative temporary pacing lead implantation. The model had good discrimination in both the derivation and validation cohorts, with the area under the receiver operating characteristic curves (AUCs) of 0.621 (95% CI = 0.602-0.640) and 0.616 (95% CI = 0.579-0.651), respectively, and showed good calibration. Compared with CHA2DS2-VASc, HATCH score, and the prediction model of POAF after CABG developed based on a small sample of clinical data from a single center in China, the model in this study had better discrimination. Conclusion: We have developed and validated a new prediction model of POAF after CABG using multicenter data that can be used in the clinic for early identification of high-risk patients of POAF, and to help effectively prevent POAF in postoperative patients.

Myo1b promotes tumor progression and angiogenesis by inhibiting autophagic degradation of HIF-1α in colorectal cancer.

Myosin 1b (Myo1b) is an important single-headed membrane-associated motor of class I myosins that participate in many critical physiological and pathological processes. Mounting evidence suggests that the dysregulation of Myo1b expression has been extensively investigated in the development and progression of several tumors. However, the functional mechanism of Myo1b in CRC angiogenesis and autophagy progression remains unclear. Herein, we found that the expression of Myo1b was upregulated in CRC tissues and its high expression was correlated with worse survival. The overexpression of Myo1b promoted the proliferation, migration and invasion of CRC cells. Conversely, silencing of Myo1b suppressed tumor progression both in vitro and in vivo. Further studies indicated that Myo1b inhibited the autophagosome-lysosome fusion and potentiated the VEGF secretion of CRC cells to promote angiogenesis. Mechanistically, Myo1b blocked the autophagic degradation of HIF-1α and then led to the accumulation of HIF-1α, thus enhancing VEGF secretion and then promoting tumor angiogenesis in CRC. Together, our study provided novel insights into the role of Myo1b in CRC progression and revealed that it might be a feasible predictive biomarker and promising therapeutic target for CRC patients.

IL-7-Treated Periodontal Ligament Cells Regulate Local Immune Homeostasis by Modulating Treg/Th17 Cell Polarization.

Both interleukin (IL)-7 and human periodontal ligament cells (hPDLCs) have immunomodulatory properties. However, their combined effect on CD4+T cells has never been studied. In this study, we aimed to investigate the effect of conditioned medium of hPDLCs treated with rhIL-7 on the differentiation of CD4+T cells into regulatory T cells/T helper 17 cells (Treg/Th17 cells) and observe the effect of IL-7 on the immunomodulatory properties of PDLCs. After hPDLCs were treated with different concentrations of rhIL-7 for 24 h, the collected supernatants were used to incubate CD4+T cells for 3 days. A gamma-secretase inhibitor (DAPT) was used to suppress the activation of the Notch1 signaling pathway. Cell proliferation, apoptosis, and necrosis were determined using the cell counting kit-8 (CCK-8) and flow cytometry (FCM). The expressions of forkhead box P3 (Foxp3) in CD4+T cells and transforming growth factor (TGF-ß) and IL-6 in the supernatants were determined by ELISA. Reverse transcription-quantitative PCR (RT-qPCR), and the Western blot (WB) determined the mRNA levels and protein expression of various target factors. FCM was used to detect the mean fluorescence intensity of PD-L1 in hPDLCs and to analyze the differentiation of Treg/Th17 cells. Our results showed that IL-7 promoted proliferation and inhibited apoptosis in hPDLCs, promoted the expression of TGF-ß, PD-L1, Notch1, Jagged1, and Hes1, and inhibited the levels of hypoxia-inducible factor (HIF)-1α and TCF7, whereas the addition of DAPT effectively reversed these effects. Importantly, we found that the conditioned medium of hPDLCs treated with rhIL-7 promoted the polarization of CD4+T cells into Treg cells but had no significant effect on the differentiation of Th17 cells. Our study indicated that treatment of PDLCs with IL-7 can promote the polarization of CD4+T cells into Treg cells by modulating the expression of inflammatory factors and signaling molecules through activating the Notch1 signaling pathway, thus participating in the regulation of immune homeostasis in the periodontal microenvironment.

The role of atria in ventricular fibrillation after continuous-flow left ventricular assist device implantation in ovine model.

Objectives: This study attempted to explore the hemodynamics and potential mechanisms driving pulmonary circulation in status of ventricular fibrillation (VF) following continuous-flow left ventricular assist device (CF-LVAD) implantation. Methods: An ovine CF-LVAD model was built in small-tailed Han sheep, with the pump speed set as 2,400 rpm. VF was induced following ventricular tachycardia using a temporary pacemaker probe to stimulate the right and left ventricular free walls. The central venous pressure (CVP), pump flow (PF), pulmonary artery flow (PAF) and other major indicators were observed and recorded after VF. Results: Low-flow systemic and pulmonary circulation could be sustained for 60 min under VF with sinus atrial rhythm after CF-LVAD implantation. The CVP gradually increased. The mean PF declined from 1.80 to 1.20 L/min, and the mean PAF decreased from 1.62 L/min to 0.87 L/min. Under VF with atrial fibrillation, the systemic and pulmonary circulation couldn't be sustained. The CVP jumped from the 5 mmHg baseline to 12 mmHg, the mean PF rapidly decreased from 3.45 L/min to 0.79 L/min, and the PAF declined from 3.94 L/min to 0.77 L/min. Conclusion: The atrial rhythm and function might be essential for the circulation maintenance in patients with VF after CF-LVAD implantation.

[Improvement of the Dewaterability of Excess Activated Sludge with Mixed Yeasts by Degrading Extracellular Polymeric Substances].

The dewaterability of excess sludge directly affects the efficiency and cost of sludge disposal, and improving sludge dewaterability is a crucial way to reduce sludge volume. This study proposes a method to improve the dewaterability of residual sludge by using mixed yeast strains to degrade extracellular polymeric substances (EPS) in activated sludge. Firstly, the mixed cells of three yeast strains were injected into the sterilized EPS solution to investigate the degradation efficiency of EPS components. Secondly, the mixed yeast cells were supplied into the residual sludge, which was aerated for several hours while the sludge dewaterability was evaluated. The results showed that the degradation efficiencies of yeast to proteins, polysaccharides, and nucleic acids in EPS were evident, and reductions of (60.43±2.73)%, (18.94±2.39)%, and (48.30±3.37)% were achieved, respectively, within 72 hours' oscillating cultivation. The capillary suction time (CST) of the sludge decreased by (17.19±1.16)% after aeration, with 1.5 g mixed yeast wet cells added into 2 L excess sludge, (7.03±1.35)% more than that of the control test after 24 hours. Meanwhile, the total amount of EPS in sludge decreased by (17.46±3.91)% more than that in the control sludge, indicating that the yeast can improve the sludge dewaterability in-situ by degrading EPS in sludge.

Prognostic factors of trans-ethmosphenoid optic canal decompression for indirect traumatic optic neuropathy.

AIM: To investigate a possible correlation between visual acuity (VA) prognosis and the presence at baseline of various orbital and ocular signs in patients affected by indirect traumatic optic neuropathy (ITON). METHODS: From July 1st, 2012 to July 1st, 2015, 224 adults diagnosed with ITON who underwent endoscopic trans-ethmosphenoid optic canal decompression (ETOCD) were reviewed. Visual outcome before and after treatment were taken into comparison. RESULTS: Accompanied older in age, longer time to medical treatment and existence of optic canal fracture (OCF) were the independent predictors for poor postoperative VA and lower improvement degree of visual acuity (IDVA), while worse preoperative VA was predictive factor for poor postoperative VA only. Mean value of IDVA in patients with OCF was 0.19±0.30. Mean value of IDVA in patients without OCF was 0.29±0.35. IDVA in cases without OCF was significant higher than those with OCF (t=2.272, P<0.05). CONCLUSION: Patients suffered from ITON without OCF before ETOCD have better surgical outcome than those with OCF. Older in age, longer time to medical treatment and existence of OCF are independent factors for poor VA prognosis and lower IDVA. Preoperative VA is independent factor for VA prognosis only.

Enhanced performance of polyimide hybrid membranes for benzene separation by incorporating three-dimensional silver-graphene oxide.

Graphene oxide-Ag nanoparticle composites were prepared through impregnation reduction using different reactants. Transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy analyses were performed to characterize differences in the morphologies of three different Ag-GO composites. Scanning electron microscopy, transmission electron microscopy, and differential scanning calorimetry analyses were also applied to evaluate the morphology and thermal stability of the hybrid membranes. Swelling-sorption and pervaporation experiments of benzene and cyclohexane were conducted to evaluate the separation performance of hybrid membranes containing different Ag-GO composites. Results demonstrated that small Ag nanoparticles generated through impregnation reduction using Ag(NH3)2(+) and PEG were homogeneously distributed in the hybrid membranes because of moderate reduction rate. The polymide (PI) hybrid membrane exhibited high separation performance. Increase in Ag content in the Ag-GO samples led to the formation of Ag particles on the GO surface; these particles enhanced the separation performance of the hybrid membranes. When Ag-GO samples with 15 mass percent added, the hybrid membrane showed the highest separation performance and its maximum separation factor in the pervaporation experiments reached 35. It is more than three times higher than that of the GO/PI hybrid membrane. Moreover, large Ag particles were formed and aggregated during the preparation and polymerization of Ag-GO samples with high Ag contents; these particles reduced the separation performance of the hybrid membranes.