ABSTRACT Introduction: New-onset postoperative atrial fibrillation (POAF) is a common complication following coronary artery bypass grafting (CABG) surgery. Objective: To explore predictive factors and potential mechanisms of new-onset POAF in isolated off-pump CABG patients. Methods: Retrospective observational case-control study of 233 patients undergoing isolated off-pump CABG surgery between August 2018 and July 2020 at the Department of Thoracic and Cardiovascular Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School. Associations between predictor variables and new-onset POAF were identified. The main outcome was new-onset POAF after CABG surgery. Results: A total of 75 (32.19%) patients developed new-onset POAF after CABG surgery. The new-onset POAF patients had advanced age, higher baseline systolic blood pressure, more preoperative use of diuretic drug, more transfusion of blood products, atrial dilation and postoperative positive inotropic drug treatment. Nineteen variates entered the multivariable logistic regression model with a Hosmer-Lemeshow test score of 7.565 (P=0.477). Postoperative left atrial enlargement, postoperative drainage in the first 24 hours and total length of hospital stay were statistically significant, while postoperative right atrial enlargement (OR and 95% CI, 7.797 [0.200, 304.294], P=0.272) and left atrial enlargement (3.524 [1.141, 10.886], P=0.029) assessed by echocardiography had the largest OR value. Conclusion: Atrial enlargement is strongly associated with new-onset POAF in patients with isolated off-pump CABG, thus it highlights the advantage of echocardiography as a useful tool for predicting new-onset POAF. Careful monitoring and timely intervention should be considered for these patients.

Abstract Background Alpha-kinase 1 (ALPK1) is a master regulator in inflammation and has been proved to promote renal fibrosis by promoting the production of IL-1β in diabetic nephropathy (DN) mice. Pyroptosis is involved in high glucose (HG)-induced tubular cells injury, characterized by activation of Gasdermin D (GSDMD) and the release of IL-1β and IL-18, resulting in inflammatory injury in DN. It is reasonable to assume that ALPK1 is involved in pyroptosis-related tubular injury in DN. However, the mechanism remains poorly defined. Methods Immunohistochemistry (IHC) staining was performed to detect the expression of pyroptosis- and fibrosis-related proteins in renal sections of DN patients and DN mice. DN models were induced through injection of streptozotocin combined with a high-fat diet. Protein levels of ALPK1, NF-κB, Caspase-1, GSDMD, IL-1β, IL-18 and α-SMA were detected by Western blot. HK-2 cells treated with high-glucose (HG) served as an in vitro model. ALPK1 small interfering RNA (siRNA) was transfected into HK-2 cells to down-regulate ALPK1. The pyroptosis rates were determined by flow cytometry. The concentrations of IL-1β and IL-18 were evaluated by ELISA kits. Immunofluorescence staining was used to observe translocation of NF-κB and GSDMD. Results The heat map of differentially expressed genes showed that ALPK1, Caspase-1 and GSDMD were upregulated in the DN group. The expression levels of ALPK1, Caspase-1, GSDMD and CD68 were increased in renal biopsy tissues of DN patients by IHC. ALPK1expression and CD68+ macrophages were positively correlated with tubular injury in DN patients. Western blot analysis showed increased expressions of ALPK1, phospho-NF-κB P65, GSDMD-NT, and IL-1β in renal tissues of DN mice and HK-2 cells, accompanied with increased renal fibrosis-related proteins (FN, α-SMA) and macrophages infiltration in interstitial areas. Inhibition of ALPK1 attenuated HG-induced upregulation expressions of NF-κB, pyroptosis-related proteins Caspase-1, GSDMD-NT, IL-1β, IL-18, α-SMA, and pyroptosis level in HK-2 cells. Also, the intensity and nuclear translocation of NF-κB and membranous translocation of GSDMD were ameliorated in HG-treated HK-2 cells after treatment with ALPK1 siRNA. Conclusions Our data suggest that ALPK1/NF-κB pathway initiated canonical caspase-1-GSDMD pyroptosis pathway, resulting in tubular injury and interstitial inflammation of DN.

Abstract Background Ischemia-reperfusion (IR) induces increased release of extracellular vesicles in the heart and exacerbates myocardial IR injury. We have previously shown that propofol attenuates hypoxia/reoxygenation (HR)-induced injury in human umbilical vein endothelial cells (HUVECs) and that microvesicles derived from propofol-treated HUVECs inhibit oxidative stress in endothelial cells. However, the role of microvesicles derived from propofol post-treated HUVECs ((HR + P)-EMVs) in IR-injured cardiomyocytes is unclear. In this study, we aimed to investigate the role of (HR + P)-EMVs in cardiac IR injury compared to microvesicles derived from hypoxic/reoxygenated HUVECs (HR-EMVs) and to elucidate the underlying mechanisms. Methods Hypoxia/reoxygenation (HR) models of HUVECs and AC16 cells and a mouse cardiac IR model were established. Microvesicles from HR-injured HUVECs, DMSO post-treated HUVECs and propofol post-treated HUVECs were extracted by ultra-high speed centrifugation, respectively. The above EMVs were co-cultured with HR-injured AC16 cells or injected intracardially into IR mice. Flow cytometry and immunofluorescence were used to determine the levels of oxidative stress and apoptosis in cardiomyocytes. Apoptosis related proteins were detected by Western blot. Echocardiography for cardiac function and Evans blue-TTC staining for myocardial infarct size. Expression of lncCCT4-2 in EMVs and AC16 cells was analysed by whole transcriptome sequencing of EMVs and RT-qPCR. The molecular mechanism of inhibition of myocardial injury by (HR + P)-EMVs was elucidated by lentiviral knockdown of lncCCT4-2, plasmid overexpression or knockdown of CCT4, and actinomycin D assay. Results In vitro and in vivo experiments confirmed that HR-EMVs exacerbated oxidative stress and apoptosis in IR-injured cardiomyocytes, leading to increased infarct size and worsened cardiac function. Notably, (HR + P)-EMVs induced significantly less oxidative stress and apoptosis in IR-injured cardiomyocytes compared to HR-EMVs. Mechanistically, RNA sequencing of EMVs and RT-qPCR showed that lncCCT4-2 was significantly upregulated in (HR + P)-EMVs and cardiomyocytes co-cultured with (HR + P)-EMVs. Reduction of lncCCT4-2 in (HR + P)-EMVs enhanced oxidative stress and apoptosis in IR-injured cardiomyocytes. Furthermore, the anti-apoptotic activity of lncCCT4-2 from (HR + P)-EMVs was achieved by increasing the stability of CCT4 mRNA and promoting the expression of CCT4 protein in cardiomyocytes. Conclusions Our study showed that (HR + P)-EMVs uptake by IR-injured cardiomyocytes upregulated lncCCT4-2 in cardiomyocytes and promoted CCT4 expression, thereby inhibiting HR-EMVs induced oxidative stress and apoptosis. Highlights Microvesicles from hypoxic/reoxygenated HUVECs (HR-EMVs) exacerbated oxidative stress and apoptosis in IR-injured cardiomyocytes. Microvesicles from propofol post-treated HUVECs ((HR + P)-EMVs) induced diminished oxidative stress and apoptosis in IR-injured cardiomyocytes compared with microvesicles from hypoxic/reoxygenated HUVECs (HR-EMVs). lncCCT4-2 was significantly highly expressed in (HR + P)-EMVs and cardiomyocytes co-cultured with (HR + P)-EMVs, and reduction of lncCCT4-2 in (HR + P)-EMVs enhanced oxidative stress and apoptosis in IR-injured cardiomyocytes. lncCCT4-2 inhibited HR-EMVs induced oxidative stress and apoptosis in HR-injured AC16 cells by increasing the stability of CCT4 mRNA and promoting the expression of CCT4 protein in AC16 cells.

Abstract Paeonia ostii is the representative of oil-utilized peony, its roots (PR) and leaves (PL) are discarded as by-products, resulting in a waste of resources. The exploration of extraction process of active ingredients from PR/PL is beneficial to the comprehensive utilization. In this work, the optimum process of Ultrasound-Assisted Extraction (UAEo) of total flavonoids content (TFC) from PR and PL was determined by single factor and response surface methodology. The results showed that UAEo was 80 min, 1:5 g/mL, 250 W, 33.83 mg Rutin/g dw for PR and 60 min, 1:10 g/mL, 250 W, 25.85 mg Rutin/g dw for PL. Then, Homogenization-Assisted Extraction (HAE), Homogenization-Ultrasound-Assisted Extraction (HUAEo) and Ultrasound-Homogenization-Assisted Extraction (UHAEo) were further analyzed. The highest PR(PL)-TFC by HUAEo at homogenization 5 min was 49.58 ± 0.25 mg/g with an increase of 46.6% (33.02 ± 0.04 mg/g with an increase of 27.7%). The highest PR/PL-total phenolic content by the HUAEo reached 77.84 ± 0.52 mg/g dw and 146.62 ± 2.77 mg/g dw for homogenization 3 min. However, there was no significant difference between HUAEo and UHAEo. In conclusion, the TFC increased with the extension of HAE time, and the combined extraction was higher yield than the single extraction.

Abstract Pain is a significant problem worldwide that affects the quality of life of patients. Dezocine is a non-addictive analgesic drug with kappa-opioid antagonist activity and has been successfully used to alleviate of postoperative pain. In addition, dezocine has an analgesic effect similar to that of morphine, alleviating moderate to severe pain. Rap guanine nucleotide exchange factor 3 (RAPGEF3) is a guanine nucleotide exchange factor for GTPases Rap1 and Rap2, which could enhance the activity of Rap1 to promote cell adhesion and axon regeneration, as well as promote neurite extension by interacting with nerve growth factors. Here, we first observed that overexpression of RAPGEF3 increased cell viability, as shown by a CCK-8 assay, and recovered brain function in rats. The expression of inflammation-related factors at the mRNA level was detected using qPCR, and the concentration of these factors in a cultured cell medium and rat serum samples were decreased as shown by ELISA after RAPGEF3 overexpression. Through western blotting, we further found that pro-inflammatory proteins were decreased, and these effects might be mediated by inhibition of the Ras/p-38 MAPK signaling pathway. Taken together, we speculated that RAPGEF3overexpression enhances the therapeutic effect of dezocine on neuropathic pain by inhibiting the inflammatory response through inhibition of the Ras/p-38 MAPK signaling pathway.

Abstract A large number of cracks occur in concrete structure after projectile penetration. The study of crack distribution and propagation process is the basis of damage assessment, structural repair and high dynamic fracture mechanism. In this paper, wire saw cutting, X-ray computed tomography (X-CT) and mechanical property testing of damaged concrete were carried out on deep penetration targets. According to X-CT images of radial core samples in target and the mechanical properties of damaged concrete, the crack distribution in the target was divided into a plastic damage zone and a brittle damage zone, and the microcracks only existed in the plastic damage zone. The initial growth process of three-dimensional cracks was obtained by X-CT images of axial core samples in target, that is, the cracks in the pure mortar target gradually developed from the radial direction to the tangential direction, and the target containing coarse aggregate directly formed tangential cracks. The propagation progress of cracks was obtained through the target section, that is, the tangential cracks bent in the pure mortar target, and were relatively straight in the target containing coarse aggregate. A crack propagation model was established, and the tangential crack formula and the crack propagation velocity were obtained.

Abstract Response surface methodology (RSM) was used to optimize the ultrasound-assisted extraction parameters of perilla protein isolate (PPI), which has functional properties. A central composite experimental design was applied to investigate the effects of three factors (ultrasonic power, extraction time, and liquid-to-solid ratio) on six responses: protein yield, water solubility index (WSI), water absorption capacity (WAC), oil holding capacity (OHC), emulsifying activity (EA), and foaming ability (FA). Based on the RSM results, the optimum conditions were an ultrasonic power of 206 W, and extraction time of 32.4 min, and a liquid-to-solid ratio of 10.34:1. Under these conditions, PPI had high protein yield (26.1%) and functional properties (55.2% WSI, 3.6% WAC, 1.76 g/g OHC, 60.25 m2/g EA, 63.2% FA). Differential scanning calorimetry revealed that PPI was slightly denatured at 75.16 °C, and the amount of heat required to induce this denaturation was 0.03 J/g. SDS-PAGE presented protein bands that ranged from 14.4 to 66.2 kDa. Based on its functional properties, PPI can be used in the food industry.

Abstract Deep penetration experiments were performed on five types of concrete with different coarse aggregate content. The projectile diameter was 29.9 mm, the initial velocity was 647 m/s, and the volume fraction of the coarse aggregate was between 0% and 59.0%. The damage laws and damage mechanism of the target were analyzed. The pure mortar target had the smallest radial crack origin diameter and crater depth. Too high of the coarse aggregate content led to the formation of many voids, which led to the disappearance of radial cracks, crater surface bypassing the coarse aggregate and a large reduction of crater diameter. The influence laws and mechanism of the coarse aggregate on the penetration depth were also analyzed. The increase of volume fraction of coarse aggregate was beneficial to reducing penetration depth and the increase of voids volume fraction was opposite. The penetration depth was the lowest when the volume fraction of the coarse aggregate reached the maximum and no voids formed. By modifying the static resistance stress in the Forrestal penetration formula, a penetration depth model considering the volume fractions of the coarse aggregate and voids was established. The predicted results were in good agreement with the experimental results.

Abstract Response surface methodology (RSM) was used to optimize ultrasound-assisted aqueous enzymatic extraction (UAAEE) conditions for perilla seed oil. Under the optimum conditions—which were a liquid-to-solid ratio of 4.4:1, a hydrolysis time of 2.66 h, a hydrolysis temperature of 50.87 °C and an ultrasound treatment time of 24.74 min—an oil yield of 31.34% was obtained. Comparisons of the physicochemical characteristics of oil obtained using UAAEE with those of oil obtained by solvent extraction (SE oil) and cold pressing extraction (CPE oil) revealed similar refractive indices and saponification values, but UAAEE oil had a higher iodine value and better stability against oxidation, with a low peroxide value. UAAEE oil contained higher levels of beneficial α-linolenic acid and phenolics than SE oil or CPE oil, and it also had superior efficiency in scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals.

ABSTRACT Hydroxydihydrobovolide (HDB) was for the first time isolated from Portulaca oleracea L. and then its cytotoxicity against SH-SYTY cells was studied. Moreover, a rapid and sensitive ultra-high performance liquid chromatographic (UHPLC) method with bergapten as internal standard (IS) was developed and validated to investigate the pharmacokinetics of HDB in rats after intravenous and oral administrations of extract (POE). The UHPLC analysis was performed on a Diamonsil C18 analytical column, using acetonitrile-water (35:65, v/v) as the mobile phase with UV detection at 220 nm. The calibration curve was linear over the range of 0.2-25 µg/mL in rat plasma. The average extraction recovery was from 90.1 to 98.9%, and the relative standard deviations (RSDs) of the intra- and inter-day precisions were less than 4.7 and 4.1%, respectively. The results showed that 50 µM HDB had significant cytotoxicity on the SH-SY5Y cells, which was rapidly distributed with a Tmax of 11 min after oral administration and presented a low absolute bioavailability, 4.12%.

OBJECTIVES: Pathological complete response has shown a better prognosis for patients with locally advanced rectal cancer after preoperative chemoradiotherapy. However, correlations between post-chemoradiotherapy clinical factors and pathologic complete response are not well confirmed. The aim of the current study was to identify post-chemoradiotherapy clinical factors that could serve as indicators of pathologic complete response in locally advanced rectal cancer. METHODS: This study retrospectively analyzed 544 consecutive patients with locally advanced rectal cancer treated at Sun Yat-sen University Cancer Center from December 2003 to June 2014. All patients received preoperative chemoradiotherapy followed by surgery. Univariate and multivariate regression analyses were performed to identify post-chemoradiotherapy clinical factors that are significant indicators of pathologic complete response. RESULTS: In this study, 126 of 544 patients (23.2%) achieved pathological complete response. In multivariate analyses, increased pathological complete response rate was significantly associated with the following factors: post-chemoradiotherapy clinical T stage 0-2 (odds ratio=2.098, 95% confidence interval=1.023-4.304, p=0.043), post-chemoradiotherapy clinical N stage 0 (odds ratio=2.011, 95% confidence interval=1.264-3.201, p=0.003), interval from completion of preoperative chemoradiotherapy to surgery of >7 weeks (odds ratio=1.795, 95% confidence interval=1.151-2.801, p=0.010) and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml (odds ratio=1.579, 95% confidence interval=1.026-2.432, p=0.038). CONCLUSIONS: Post-chemoradiotherapy clinical T stage 0-2, post-chemoradiotherapy clinical N stage 0, interval from completion of chemoradiotherapy to surgery of >7 weeks and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml were independent clinical indicators for pathological complete response. These findings demonstrate that post-chemoradiotherapy clinical factors could be valuable for post-operative assessment of pathological complete response.

OBJECTIVES: This study aimed to evaluate the safety and efficacy of a new nickel-titanium shape memory alloy compression anastomosis ring, NiTi CAR 27, in constructing an anastomosis for colorectal cancer resection compared with conventional staples. METHODS: In total, 234 consecutive patients diagnosed with colorectal cancer receiving sigmoidectomy and anterior resection for end-to-end anastomosis from May 2010 to June 2012 were retrospectively analyzed. The postoperative clinical parameters, postoperative complications and 3-year overall survival in 77 patients using a NiTi CAR 27 compression ring (CAR group) and 157 patients with conventional circular staplers (STA group) were compared. RESULTS: There were no statistically significant differences between the patients in the two groups in terms of general demographics and tumor features. A clinically apparent anastomotic leak occurred in 2 patients (2.6%) in the CAR group and in 5 patients (3.2%) in the STA group (p=0.804). These eight patients received a temporary diverting ileostomy. One patient (1.3%) in the CAR group was diagnosed with anastomotic stricture through an electronic colonoscopy after 3 months postoperatively. The incidence of postoperative intestinal obstruction was comparable between the two groups (p=0.192). With a median follow-up duration of 39.6 months, the 3-year overall survival rate was 83.1% in the CAR group and 89.0% in the STA group (p=0.152). CONCLUSIONS: NiTi CAR 27 is safe and effective for colorectal end-to-end anastomosis. Its use is equivalent to that of the conventional circular staplers. This study suggests that NiTi CAR 27 may be a beneficial alternative in colorectal anastomosis in Chinese colorectal cancer patients.

The reaction mechanism between azacyclopropenylidene and azacyclopropane has been systematically investigated employing the second-order Møller-Plesset perturbation theory (MP2) method to better understand the azacyclopropenylidene reactivity with three-membered ring compound azacyclopropane. Geometry optimization, vibrational analysis, and energy property for the involved stationary points on the potential energy surface have been calculated. For the first step of this reaction, azacyclopropenylidene can insert into azacyclopropane at its C-N bond to form a spiro intermediate IM. Through the ring-opened step at C-C bond of azacyclopropenylidene fragment, IM can transfer to product P1, which is named as pathway (1). On the other hand, through the H-transferred step and subsequent ring-opened step at C-N bond of azacyclopropenylidene fragment, IM can turn into product P2, which is named as pathway (2). From the thermodynamics viewpoint, the P2 is the dominating product. From the kinetic viewpoint, the pathway (1) of formation to P1 is primary.

The mechanism of addition reaction between the singlet carbene and glycine has been investigated at the B3LYP/6-311+G* level of theory, including geometry optimization and vibrational analysis for the involved stationary points on the potential energy surface. Computational results suggest that there are two reaction pathways (1) and (2) during the addition process. In the pathway (1), carbene attacks the C=O bond from the H¹C¹C² side of glycine to form an intermediate (IM1), which is a barrier-free exothermic reaction. Then, IM1 isomerizes to a product (Pro1) via a transition state (TS1) with a potential barrier of 25.7 kJ/mol. Similarly, in the pathway (2), carbene attacks the C=O bond from the H²C¹C² side of glycine to form an intermediate IM2. Subsequently, IM2 isomerizes to Pro2 via TS2, where the Pro2 and Pro1 are enantiomers actually. The calculated potential barrier of 51.3 kJ/mol is higher than that of the pathway (1). Correspondingly, the reaction energy for the both pathways is -258.5 kJ/mol. Additionally, the atoms in molecules (AIM) theory has also been performed to characterize the bonding interaction and structural features for the addition reaction.

Zhikong scallop Chlamys farreri (Jones et Preston) is an economically important species in China. Understanding its immune system would be of great help in controlling diseases. In the present study, an important immunity-related gene, the Lipopolysaccharide and Beta-1,3-glucan Binding Protein (LGBP) gene, was located on C. farreri chromosomes by mapping several lgbp-containing BAC clones through fluorescence in situ hybridization (FISH). Through the localization of various BAC clones, it was shown that only one locus of this gene existed in the genome of C. farreri, and that this was located on the long arm of a pair of homologous chromosomes. Molecular markers, consisting of eight single nucleotide polymorphism (SNPs) markers and one insertion-deletion (indel), were developed from the LGBP gene. Indel marker testing in an F1 family revealed slightly distorted segregation (p = 0.0472). These markers can be used to map the LGBP gene to the linkage map and assign the linkage group to the corresponding chromosome. Segregation distortion of the indel marker indicated genes with deleterious alleles might exist in the surrounding region of the LGBP gene.