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The effects of repeated freeze-thaw (F-T) treatments on the oxidation and degradation of muscle proteins from mirror carp (Cyprinus carpio L.) were investigated. The myofibrillar fragmentation index, trichloroacetic acid-soluble peptides, total volatile basic nitrogen, amino nitrogen, and carbonyl content of the samples significantly increased (P 0.05). However, the samples showed a significant reduction in the fragmentation index, myofibrillar protein (MP) solubility, and total sulfhydryl content after five F-T cycles (P 0.05). Moreover, the sodium dodecyl sulfate-polyacrylamide gel electrophoresis bands of the MP faded because of the oxidation and degradation of the protein with increasing F-T cycles. By the fifth F-T cycle, the α-helix and β-turn content significantly decreased by 10.41 % and 5.72 %, respectively (P 0.05), whereas the β-sheet and random coil content significantly rose by 7.66 % and 8.47 %, respectively (P 0.05). Furthermore, the intrinsic fluorescence of the MP showed a substantial decrease in intensity and a redshift. In summary, iterative F-T cycles destroyed the MP structure and caused the oxidation and degradation of muscle proteins from mirror carp.

Structural water molecules adsorbed on Au nanoparticles in the form of {OH−·H2O@Au NPs} were identified as catalytical-active sites of 4-nitrophenol reduction, which is extremely sensitive to the subtle changes in the surrounding microenvironment.

Ganoderma lucidum polysaccharide (GLPS) can inhibit hepatocellular carcinoma (HCC). But the mechanism of GLPS's effect is little known. This data showed that GLPS can regulate MAPK/NF-κB signaling responsible for M1 polarization in anti-HCC.

The palladium-catalyzed rearrangement of VCPs (dienyl or trienyl cyclopropanes) for the construction of functionalized cyclopentene units was reported in high yields and with excellent regioselectivities and enantioselectivities.

Obesity hypoventilation syndrome (OHS) is frequently misdiagnosed and undertreated, increasing the risk of perioperative complications. We aimed to determine the predictors of OHS and to develop and validate a novel nomogram and online calculator for identifying patients at risk of OHS in bariatric surgery candidates.We retrospectively analyzed the data of patients undergoing bariatric surgery between March 2017 and June 2020. Predictors were identified using univariate and multivariate analyses to establish the nomogram. The discriminative ability, calibration, and clinical value of the nomograms were tested using C-statistics, calibration plots, and decision curve analysis. The nomogram was internally validated using bootstrap resampling.A total of 577 patients were enrolled, and OHS was presented in 17.9% (103/577). Body mass index (BMI) (odds ratio [OR], 1.11; 95% confidence interval (CI), 1.04-1.18; p = 0.001), neck circumference (OR, 1.09; 95% CI, 1.01-1.18; p = 0.035), type 2 diabetes (T2D) (OR, 2.02; 95% CI, 1.17-3.45; p = 0.011), serum bicarbonate (OR, 1.47; 95% CI, 1.30-1.67; p 0.001), and C-reactive protein (CRP) (OR, 1.03; 95% CI, 1.01-1.06; p = 0.017) were independent risk factors for OHS and incorporated to develop the nomogram. The nomogram revealed good discrimination, with a C-index of 0.830 (95% CI: 0.784-0.876) (0.8227 through internal validation), and good calibration. Decision curve analysis further confirmed the nomogram's clinical usefulness.The novel nomogram and online calculator provided an excellent preoperative individualized prediction of OHS in patients undergoing bariatric surgery, hereby potentially assisting clinicians and surgeons in the early detection and intensive monitoring of OHS.

The objective of this study was to evaluate the value of tumor morphology, long-to-short diameter ratio (L/S), and ultrasound gray-scale ratio (UGSR) in the differential diagnosis of 3 parotid neoplasms.Preoperative ultrasound images of 17 patients with a malignant tumor (MT), 48 patients with pleomorphic adenoma (PA), and 39 patients with adenolymphoma (AL) were analyzed for imaging features and gray-scale histograms. Tumor morphology, L/S, and UGSR of MT, PA, and AL were compared. Receiver operating characteristic analysis of area under the curve (AUC), sensitivity, and specificity were used to measure the differential diagnostic efficacy of L/S, UGSR, and both combined with tumor morphology.Morphologic features, L/S, and UGSR differed significantly in various pairwise comparisons of the 3 tumor types. Acceptable discrimination was detected between MT and AL with UGSR alone (AUC = 0.771) and between PA and AL with L/S and UGSR combined (AUC = 0.741). The combination of tumor boundary with UGSR yielded excellent discrimination between MT and PA (AUC = 0.853) and between MT and AL (AUC = 0.885), with sensitivity and specificity values greater than 0.800.These ultrasound parameters, alone or in combination, can provide a method for accurate presurgical differential diagnosis of parotid tumors.

Regenerative medicine and tissue engineering have delivered new healing possibilities to the treatment of soft tissue defects, but the selection of seed cells is critical for treatment. Adipose-derived stem cells have perpetually been a preferred candidate for seed cells due to their wealthy sources, simple access, high plasticity, and powerful value-added capabilities. How to improve the efficiency of adipogenic differentiation is the key to the treatment. Pituitary adenylate cyclase-activating peptide, as a biologically active peptide secreted by the pituitary, is widely involved in regulating the body's sugar metabolism and lipid metabolism. However, the effects of MPAPO in ADSCs adipogenic differentiation remain unknown. Our results reveal that MPAPO treatment improves the adipogenic differentiation efficiency of ADSCs, including promoting the accumulation of lipid droplets and triglycerides, and the expression of adipocyte protein biomarkers PPARγ and C/EBPa. Additionally, the mechanism studies showed that the effective window of MPAPO-induced adipogenesis was the first 3 days during ADSCs differentiation. MPAPO selectively binds to the PAC1 receptor and promotes adipogenic differentiation of ADSCs by activating the ERK signaling pathway and elevating cell proliferation during postconfluent mitosis stage. Altogether, we demonstrate that MPAPO plays a crucial role in ADSCs adipogenesis, providing experimental basis and data for exploring therapeutic options in tissue defect repair.

Despite the great advancement in atroposelective synthesis in the past decades, the enantioselective synthesis of 2,2'-difluoro-1-biaryls is unprecedented. Herein, a palladium and chiral amino acid catalyzed atroposelective C-H olefination to construct the axially chiral 2,2'-difluoro-1-biaryls is reported. A variety of polyfluoro-substituted biaryls were forged under mild conditions in good yields with excellent enantioselectivity (up to 99% ee). The potential application was demonstrated by a gram-scale synthesis and synthetic transformations.

Salvianolic acid A (SAA) is one of bioactive polyphenol extracted from a Salvia miltiorrhiza (Danshen), which was widely used to treat cardiovascular disease in traditional Chinese medicine. SAA has been reported to be protective in cardiovascular disease and ischemia injury, with anti-inflammatory and antioxidative effect, but its role in acute lung injury (ALI) is still unknown. In this study, we sought to investigate the therapeutic effects of SAA in a murine model of lipopolysaccharide- (LPS-) induced ALI. The optimal dose of SAA was determined by comparing the attenuation of lung injury score after administration of SAA at three different doses (low, 5 mg/kg; medium, 10 mg/kg; and, high 15 mg/kg). Dexamethasone (DEX) was used as a positive control for SAA. Here, we showed that the therapeutic effect of SAA (10 mg/kg) against LPS-induced pathologic injury in the lungs was comparable to DEX. SAA and DEX attenuated the increased W/D ratio and the protein level, counts of total cells and neutrophils, and cytokine levels in the BALF of ALI mice similarly. The oxidative stress was also relieved by SAA and DEX according to the superoxide dismutase and malondialdehyde. NET level in the lungs was elevated in the injured lung while SAA and DEX reduced it significantly. LPS induced phosphorylation of Src, Raf, MEK, and ERK in the lungs, which was inhibited by SAA and DEX. NET level and phosphorylation level of Src/Raf/MEK/ERK pathway in the neutrophils from acute respiratory distress syndrome (ARDS) patients were also inhibited by SAA and DEX in vitro, but the YEEI peptide reversed the protective effect of SAA completely. The inhibition of NET release by SAA was also reversed by YEEI peptide in LPS-challenged neutrophils from healthy volunteers. Our data demonstrated that SAA ameliorated ALI via attenuating inflammation, oxidative stress, and neutrophil NETosis. The mechanism of such protective effect might involve the inhibition of Src activation.

The 3D printed porous titanium alloy scaffolds are beneficial to enhance angiogenesis, osteoblast adhesion, and promote osseointegration. However, titanium alloys are biologically inert, which makes the bond between the implant and bone tissue weak and prone to loosening. Inspired by the natural biological marine mussels, we designed four-claw-shaped mussel-derived bioactive peptides for the decoration of porous titanium alloy scaffolds: adhesion peptide-DOPA, anchoring peptide-RGD and osteogenic-inducing peptide-BMP-2. And the bifunctionalization of 3D-printed porous titanium alloy scaffolds was evaluated in vivo in a rabbit model of bone defect with excellent promotion of osseointegration and mechanical stability. Our results show that the in vivo osseointegration ability of the modified 3D printed porous titanium alloy test piece is significantly improved, and the bifunctional polypeptide coating group E has the strongest osseointegration ability. In conclusion, our experimental design partially solves the problems of stress shielding effect and biological inertness, and provides a convenient and feasible method for the clinical application of titanium alloy implants in biomedical implant materials.

The immunologic features involved in the immune-tolerant phase of chronic hepatitis B (CHB) virus (HBV) infection are unclear. The hepatitis B virus X (HBx) protein disrupts IFN-β induction by downregulating MAVS and may destroy subsequent HBV-specific adaptive immunity. We aimed to analyse the impacts of genetic variability of HBx in CHB patients on the immune-tolerant phase during long-term follow-up.Children with CHB in the immune-tolerant phase were recruited and followed longitudinally. HBx gene sequencing of infecting HBV strains was performed, and the effects of HBx mutations on the immune-tolerant phase were assessed. Restoration of the host immune response to end the immune-tolerant phase was investigated by immunoblotting, immunostaining, ELISA and reporter assays of MAVS/IFN-β signalling in liver cell lines, patient liver tissues and the HBV plasmid replication system.A total of 173 children (median age, 6.92 years) were recruited. Patients carrying HBx R87G, I127V and R87G + I127V double mutations exhibited higher cumulative incidences of immune-tolerant phase breakthrough (p = .011, p = .006 and p = .017 respectively). Cells transfected with HBx R87G and I127V mutants and pHBV1.3-B6.3 replicons containing the HBx R87G and I127V mutations exhibited statistically increased levels of IFN-β, especially under poly(I:C) stimulation or Flag-MAVS cotransfection. HA-HBx wild-type interacted with Flag-MAVS and enhanced its ubiquitination, but this ability was diminished in the R87G and I127V mutants.HBx suppresses IFN-β induction. R87G and I127V mutation restored IFN-β production by preventing MAVS degradation, contributing to curtailing the HBV immune-tolerant phase in CHB patients.

IntroductionAcute ischemic stroke (AIS) and lung adenocarcinoma (LUAD) are associated with some of the highest morbidity and mortality rates worldwide. Despite reports on their strong correlation, the causal relationship is not fully understood. The study aimed to identify and annotate the biological functions of hub genes with clinical diagnostic efficacy in AIS and LUAD.MethodsTranscriptome and single-cell datasets were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). We identified the differentially expressed genes (DEGs) upregulated in AIS and LUAD and found 372 genes intersecting both datasets. Hub genes were identified using protein-protein interaction (PPI) networks, and the diagnostic and prognostic utility of these hub genes was then investigated using receiver operating characteristic (ROC) curves, survival analysis, and univariable Cox proportional hazard regression. Single-cell analysis was used to detect whether the hub genes were expressed in tumor epithelial cells. The immune microenvironment of AIS and LUAD was assessed using the CIBERSORT algorithm. The protein expression of these hub genes was tracked using the Human Protein Atlas (HPA). We calculated the number of positive cells using the digital pathology software QuPath. Finally, we performed molecular docking after using the Enrichr database to predict possible medicines.ResultsWe identified the molecular mechanisms underlying hub genes in AIS and LUAD and found that CCNA2, CCNB1, CDKN2A, and CDK1 were highly expressed in AIS and LUAD tissue samples compared to controls. The hub genes were mainly involved in the following pathways: the cell cycle, cellular senescence, and the HIF-1 signaling pathway. Using immunohistochemical slices from the HPA database, we confirmed that these hub genes have a high diagnostic capability for AIS and LUAD. Further, their high expression is associated with poor prognosis. Finally, curcumin was tested as a potential medication using molecular docking modeling.DiscussionOur findings suggest that the hub genes we found in this study contribute to the development and progression of AIS and LUAD by altering the cellular senescence pathway. Thus, they may be promising markers for diagnosis and prognosis.

We synthesized and assembled a truncated cyanophage genome called Syn-P4-8, containing 18 genes for viral coat assembly proteins, and transferred it into a nonhost strain, Synechocystis sp. PCC 6803, to investigate interactions between Syn-P4-8 and Synechocystis PCC 6803. We found that coexpression of tail fiber and tail protein genes enhanced the salt tolerance of Synechocystis PCC 6803.

The development of new antifungal drugs is critical for solving the problem of antifungal resistance and expanding the limited variety of clinical antifungal drugs. Based on the modification of the pyrylium salt SM21, a new lead compound, xy12, was synthesized which was effective against Candida species both in vitro and in vivo .

Taking NVP-BEZ235 (BEZ235) as an example to screen drug response-related genes (DRRGs) and explore their potential value in triple-negative breast cancer (TNBC). Through high-throughput technique, multidimensional transcriptome expression data (mRNA, miRNA and lncRNA) of BEZ235-treated and -untreated MDA-MB-468 cell lines were obtained. Combined with transcriptome data of the MDA-MB-468 cells and TCGA-TNBC tissues, differential gene expression analysis and WGCNA were performed to identify DRRGs associated with tumor trait by simulating the drug response microenvironment (DRM) of BEZ235-treated patients. Based on DRRGs, we constructed a ceRNA network and verified the expression levels of three key molecules by RT-qPCR, which not only demonstrated the successful construction of a BEZ235-treated cell line model but also explained the antitumor mechanism of BEZ235. Four molecular subtypes related to the DRM with survival difference were proposed using cluster analysis, namely glycolysis subtype, proliferation depression subtype, immune-suppressed subtype, and immune-activated subtype. A novel prognostic signature consisting of four DRRGs was established by Lasso–Cox analysis, which exhibited outstanding performance in predicting overall survival compared with several excellent reported signatures. The high- and low-risk groups were characterized by enrichment of metabolism-related pathways and immune-related pathways, respectively. Of note, the low-risk group had a better response to immune checkpoint blockade. Besides, pRRophetic analysis found that patients in the low-risk group were more sensitive to methotrexate and cisplation, whereas more resistant to BEZ235, docetaxel and paclitaxel. In conclusion, the DRRGs exemplified by BEZ235 are potential biomarkers for TNBC molecular typing, prognosis prediction and targeted therapy. The novel DRRGs-guided strategy for predicting the subtype, survival and therapy efficacy, might be also applied to more cancers and drugs other than TNBC and BEZ235.

Background and purpose Tumor recurrence after liver transplantation (LT) impedes the curative chance for hepatocellular carcinoma (HCC) patients. This study aimed to develop a deep pathomics score (DPS) for predicting tumor recurrence after liver transplantation using deep learning. Patients and methods Two datasets of 380 HCC patients who underwent LT were enrolled. Residual convolutional neural networks were used to identify six histological structures of HCC. The individual risk score of each structure and DPS were derived by a modified DeepSurv network. Cox regression analysis and Concordance index were used to evaluate the prognostic significance. The cellular exploration of prognostic immune biomarkers was performed by quantitative and spatial proximity analysis according to three panels of 7-color immunofluorescence. Results The overall classification accuracy of HCC tissue was 97%. At the structural level, immune cells were the most significant tissue category for predicting post-LT recurrence (HR 1.907, 95% CI 1.490–2.440). The C-indices of DPS achieved 0.827 and 0.794 in the training and validation cohorts, respectively. Multivariate analysis for recurrence-free survival (RFS) showed that DPS (HR 4.795, 95% CI 3.017–7.619) was an independent risk factor. Patients in the high-risk subgroup had a shorter RFS, larger tumor diameter and a lower proportion of clear tumor borders. At the cellular level, a higher infiltration of intratumoral NK cells was negatively correlated with recurrence risk. Conclusions This study established an effective DPS. Immune cells were the most significant histological structure related to HCC recurrence. DPS performed well in post-LT recurrence prediction and the identification of clinicopathological features.

As a part of the Columbia supercontinent, the North China craton is an ideal object for studying the evolution of supercontinent assembly and the mechanism of orogenesis in the Paleoproterozoic. The Jiao-Liao-Ji belt, located in the eastern part of the North China craton, provides important clues for our understanding of Paleoproterozoic orogenic processes. A series of Paleoproterozoic granitic gneiss domes is preserved in the Liaodong segment of the Jiao-Liao-Ji belt. These domes are cored by the Liaoji granitic gneisses (emplaced at 2250−2150 Ma) and mantled by metamorphosed volcanic-sedimentary rocks (deposited at 2200−1940 Ma). Combining multiple lines of evidence from mesostructures and microstructures, kinematics, magnetic fabrics, and crystallographic fabrics, we suggest that the granitic gneiss domes reflect inhomogeneous shearing of the middle to lower crust during Paleoproterozoic orogenic processes. Intensive layer-paralleling shearing characterized subhorizontal flow during nearly E-W−oriented compression. As a hot orogen formed in the Paleoproterozoic, the orogenic deformation in the Jiao-Liao-Ji belt was characterized by extensive doming due to dominant subhorizontal flow and subsidiary vertical flow in the middle to lower crust.

The objective of this study was to analyze the protein profile and amino acid composition of perch essence processed by high-pressure extraction compared with mackerel, and milkfish. The inhibitory activities of three essences were determined against digestive enzymes relevant to the metabolic syndrome such as the angiotensin-converting enzyme (ACE), pancreatic lipase, α-amylase, and α-glucosidase. The results showed that perch essence exhibits the highest recovery by using the same extraction method for all three fish species. The amounts of all hydrolyzed amino acids, except histidine, were approximately double in perch compared with the other two fish. The perch essence contained the most abundant soluble protein and amino acids composition related to metabolic syndrome. In vitro anti-hypertensive, hypoglycemic, and anti-obesity potency of perch essence exhibited the highest among the three fishes. Although the amounts of free amino acids were similar in the three fish species, the molecular weight distribution from gel filtration chromatographic analysis indicated that perch essence contained 32.4% of peptides with a molecular weight of less than 2.3 kDa. This study suggested that naturally occurring bioactive peptides in perch essence might potentially serve as a good source of functional food supplements for metabolic syndrome.

BACKGROUND/PURPOSE This study aimed to explore the anatomical and physiological characteristics of patients with laryngopharyngeal reflux (LPR) symptoms, such as hoarseness, throat clearing, throat pain, globus, and chronic cough, with the novel high-resolution impedance manometry (HRIM). METHODS Consecutive patients exhibited at least one LPR symptom for ≥4 weeks after 2-month proton-pump inhibitor treatment were enrolled during November 2014 and March 2018 from single tertiary medical center. All patients completed validated symptom questionnaires, esophagogastroduodenoscopy, and HRIM. Healthy volunteers were also recruited for comparison of esophageal parameters on HRIM. RESULTS Eighty-nine LPR patients and 63 healthy volunteers were analyzed. Compared with healthy volunteers, LPR patients had significantly shorter upper and lower esophageal sphincters (UES and LES), a shorter intraabdominal esophagus (all P

Obesity is a world-wide problem, especially the child obesity, with the complication of various metabolic diseases. Child obesity can be developed as early as the age between 2 and 6. The expansion of fat mass in child age includes both hyperplasia and hypertrophy of adipose tissue, suggesting the importance of proliferation and adipogenesis of preadipocytes. The changed composition of gut microbiota is associated with obesity, revealing the roles of lipopolysaccharide (LPS) on manipulating adipose tissue development. Studies suggest that LPS enters the circulation and acts as a pro-inflammatory regulator to facilitate pathologies. Nevertheless, the underlying mechanisms behind LPS-modulated obesity are yet clearly elucidated. This study showed that LPS enhanced the expression of cyclooxygenase-2 (COX-2), an inflammatory regulator of obesity, in preadipocytes. Pretreating preadipocytes with the scavenger of reactive oxygen species (ROS) or the inhibitors of NADPH oxidase or p42/p44 MAPK markedly decreased LPS-stimulated gene expression of COX-2 together with the phosphorylation of p47