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AimTo investigate the interactions between the graft-to-recipient weight ratio (GWRWR) and other risk factors responsible for inferior allograft outcomes.MethodsA total of 362 patients who received liver transplantation (LT) were enrolled. Indicators such as graft/recipient weight and other prognostic factors were collected. Comparisons of indicators and survival analysis were performed in groups categorized by the GWRWR. Interactions of large-for-size grafts (LFSGs) with graft macrosteatosis (MaS) were evaluated in terms of relative excess risk caused by interaction (RERI) and attributable proportion (AP). Cytoscape visualized the role of LFSGs in the risk profile for poor prognosis.ResultsBased on the GWRWR, LT cases can be categorized into three subgroups, standard (1%–2.5%), optimal (2.5%–3.0%), and inferior prognosis (>3.0%). Survival analysis confirmed clear separations in cases categorized by the above-defined limits on the GWRWR (P 3.0%) caused inferior outcomes, while grafts sized within (2.5%–3.0%) had optimal post-transplant prognosis. MaS increased the risk of poor prognosis by exerting positive synergistic effects on LFSGs.

BackgroundPatients with gallstone disease (GSD) often have highly co-occurrence with metabolic syndrome (MetS) and Nonalcoholic fatty liver disease (NAFLD) both associated with insulin resistance (IR). Meanwhile, highly prevalence of NAFLD was found in patients who received cholecystectomy. However, the associations of GSD with MetS, NAFLD is inconsistent in the published literature. And risk of cholecystectomy on NAFLD is unclear.MethodsWe searched the Medline EMBASE and WOS databases for literature that met our study topic. To be specific, studies with focus on associations between GSD and MetS/NAFLD, and risk evaluation on cholecystectomy and NAFLD incidence were enrolled for further analysis. The random effect model was used to calculate the combined relative ratio (RR) and odds ratio (OR)and 95% confidence interval (CI).ResultsSeven and six papers with focus on connections between GSD and NAFLD/MetS prevalence. Correspondingly, seven papers with focus on risk of cholecystectomy on NAFLD occurrence were also enrolled into meta-analysis. After pooling the results from individual study, patients with GSD had higher risk of MetS (OR:1.45, 95%CI: 1.23-1.67, I2 = 41.1%, P=0.165). Risk of GSD was increased by 52% in NAFLD patients (pooled OR:1.52, 95%CI:1.24-1.80). And about 32% of increment on NAFLD prevalence was observed in patients with GSD (pooled OR: 1.32, 95%CI:1.14-1.50). With regard to individual MetS components, patients with higher systolic blood pressure were more prone to develop GSD, with combined SMD of 0.29 (96%CI: 0.24-0.34, P

Two novel discrete organoplatinum(II) metallacycles are prepared by means of coordination-driven self-assembly of a 90° organoplatinum(II) acceptor, cis-(PEt3)2Pt(OTf)2, with two donors, a pyridyl donor, 9,10-di(4-pyridylvinyl)anthracene, and one of two dicarboxylate ligands. Both metallacycles display aggregation-induced emission as well as solvatochromism. More interestingly, both metallacycles exhibit near-infrared fluorescent emission in the solid state and can be used to detect ammonia gas. [ABSTRACT FROM AUTHOR]

As a Ca2+-permeable cationic channel, canonical transient receptor potential 5 channel (TRPC5) has been known to be involved in various functions of cells. Although TRPC5 is abundantly expressed in vascular endothelium, it remains unknown whether TRPC5 plays a role in regulating endothelial senescence. In the present study, we investigated the involvement of TRPC5 in the senescence of mouse aortic endothelial cells (MAECs). Meanwhile, the regulatory role of TRPC5 in the endothelial dysfunction in aged mice was also studied. Results showed that the endothelium-dependent relaxations were significantly promoted but the endothelium-dependent contractions were markedly attenuated in aortic rings from aged mice with TRPC5 gene knocked out compared with those from aged C57BL/6J mice. Meanwhile, the nuclear telomerase activity and nitric oxide generation were notably enhanced but the reactive oxygen species production was significantly inhibited in aged mice or in hydrogen peroxide-induced senescent MAECs lacking the TRPC5 gene. In addition, by performing the senescence-associated β-galactosidase staining the oxidative stress-induced premature senescence was markedly depressed in MAECs with TRPC5 gene deficient. Expressions of endothelial nitric oxide synthase and silent information regulator protein 1 (SIRT1) were significantly up-regulated but those of P53 and P21 were markedly down-regulated both in aged mice and in hydrogen peroxide-treated MAECs in the absence of the TRPC5 gene. These results of our study uncover novel functions of TRPC5 in regulating vascular aging. [ABSTRACT FROM AUTHOR]

Objective To explore the mechanism of miR-223-3p regulating the occurrence and development of liver cancer cells by targeting FAT1 gene. Methods Bioinformatics analysis was used to analyze the differentially expressed genes in liver cancer tissue chips. Forty-eight cases of liver cancer tissues and corresponding adjacent tissues were selected, and qRT-PCR was used to detect the expression of miR-223-3p and FAT1mRNA in tissues. Wound healing assay was used to detect the migration ability of liver cancer cells. Transwell assay was used to detect cells invasion ability. Dual-luciferase assay was used to detect the targeting relationship between miR-223-3p and FAT1. Western blot was used to detect the protein expression of EMT-related markers, E-cadherin and Vimentin. Results FAT1 was highly expressed in liver cancer tissues and cells, while miR-223-3p was lowly expressed. Silencing FAT1 could inhibite the proliferation, migration, invasion and EMT of liver cancer cells. miR-223-3p targeted down-regulated the expression of FAT1, and inhibited the proliferation, migration, invasion and EMT of liver cancer cells by targeting FAT1. Conclusion miR-223-3p regulates the occurrence and development of liver cancer cells by targeted down-regulating the expression of FAT1.

Background: Low-grade glioma (LGG) is considered a fatal disease for young adults, with overall survival widely ranging from 1 to 15 years depending on histopathologic and molecular subtypes. As a novel type of programmed cell death, ferroptosis was reported to be involved in tumorigenesis and development, which has been intensively studied in recent years.Methods: For the discovery cohort, data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) were used to identify the differentially expressed and prognostic ferroptosis-related genes (FRGs). The least absolute shrinkage and selection operator (LASSO) and multivariate Cox were used to establish a prognostic signature with the above-selected FRGs. Then, the signature was developed and validated in TCGA and Chinese Glioma Genome Atlas (CGGA) databases. By combining clinicopathological features and the FRG signature, a nomogram was established to predict individuals’ one-, three-, and five-year survival probability, and its predictive performance was evaluated by Harrell’s concordance index (C-index) and calibration curves. Enrichment analysis was performed to explore the signaling pathways regulated by the signature.Results: A novel risk signature contains seven FRGs that were constructed and were used to divide patients into two groups. Kaplan–Meier (K−M) survival curve and receiver-operating characteristic (ROC) curve analyses confirmed the prognostic performance of the risk model, followed by external validation based on data from the CGGA. The nomogram based on the risk signature and clinical traits was validated to perform well for predicting the survival rate of LGG. Finally, functional analysis revealed that the immune statuses were different between the two risk groups, which might help explain the underlying mechanisms of ferroptosis in LGG.Conclusion: In conclusion, this study constructed a novel and robust seven-FRG signature and established a prognostic nomogram for LGG survival prediction.

In this paper, 6061-T6 aluminum alloy and 30CrMnSiA steel are bonded by inertia radial friction welding (IRFW). The formation mechanism of the aluminum/steel friction welded joints and the effect of the welding parameters on the mechanical properties are investigated through the microstructure, microzone composition, and mechanical property analysis. The results show that no visible intermetallic compound layers (IMCs) are detected on the aluminum/steel welding interface, which may be due to Si element aggregating in the welding interface and then forming a Al−Fe−Si phase, preventing the formation and growth of an Al−Fe IMCs. Eventually, a micron ultrathin interface reaction layer composed of Al0.7Fe3Si0.3, FeAl, and Fe3Al phases is formed at the aluminum/steel welding interface. The maximum average shear strength of the joint is 176 MPa. The shear fracture is a typical ductile fracture. Properly reducing the friction speed and increasing the upsetting pressure can improve the bonding strength of aluminum/steel joints.

Background: Donor age affects allograft quality and the prognosis of recipients after liver transplantation (LT). Clinicians have assessed the quality of grafts from older donors based on their appearance and texture, with no reliable quantitative evidence. Our study aimed to assess the quantitative impact of donor age on post-transplant outcomes and its safety threshold for LT, based on the published literature.Methods: Relevant studies were retrieved from the Embase, PubMed, and ISI Web of Science databases. Pooled dichotomous relative risks (RRs) were calculated using metan. Continuous RRs were calculated using a two-stage random-effects model.Results: Eleven studies including 30,691 LT cases were included for further analysis. For categorical comparison, the RR of death within the first post-transplant year was significantly higher among patients who received grafts from older donors. Similarly, the RR of graft failure (GF) was increased within the 3 years after transplantation. For continuous comparison, advanced donor age affected transplant outcomes in a linear manner (P > 0.05). A 10-year increment in donor age was associated with RRs 1.10, 1.12, 1.15, 1.10, and 1.08 for 90-day, 180-day, 1-year, 3-year, and 5-year patient mortality and 1.08, 1.06, 1.10, 1.11, and 1.12, for 90-day, 180-day, 1-year, 2-year, and 3-year GF, respectively (all P < 0.05). A spline model showed that transplants using grafts from donors 0.05). The risk of GF was increased in subgroups with fewer LT cases, longer cold ischemic time, fewer male donors, and recipients with viral hepatitis (P < 0.05).Conclusion: Donor age might affect post-LT outcomes in a dose-dependent manner. The safety threshold for donor age in terms of GF should be lowered to 43 years as an early warning for the guarantee of satisfactory outcomes. Clinicians should weigh the benefits against the risks carefully for patients receiving grafts from older donors. Further studies are warranted to investigate the mechanisms responsible for the relationship between donor age and graft quality.

Ammonia has been of concern for its high toxicity to aquatic species and frequent detection in waters worldwide. This study calculated the national aquatic life criteria for ammonia in China. The temporal and spatial distributions were investigated and the multi-tier ecological risks were assessed for ammonia and un-ionized ammonia (NH3) during 2014–2018 based on a total of 18989 ammonia monitoring data from 110 monitoring sites in seven river basins. The sensitivity comparison of different species taxa to ammonia showed that Perciformes fish should be listed as a priority protected species in the derivation of ammonia criteria. The participation of introduced aquaculture species have no significant impact on the final criteria values (t-test, p > 0.05). The final criterion maximum concentration (CMC) and criterion continuous concentration (CCC) were 10.24 and 3.31 mg/L for ammonia (pH 7.0 and 20 °C). The interannual variation showed that decreasing trends were observed for ammonia and NH3 pollutions in the past five years. However, the increasing trends were observed for ammonia in Liao River basin, for NH3 in Yangtze River and Pearl River basins (2014–2018). The significant seasonal and geographical differences of ammonia and NH3 pollution were found. Moreover, the pollutions of ammonia and NH3 in some monitoring points of Huai River, Yellow River and Songhua River basins at the provincial borders were significant. The result of ecological risk assessment showed that the average exceedance probability for 5% affected species by NH3 in long-term exposure was 28.96% in the past five years.

Background: Novel immunotherapy is one of the options for advanced biliary tract cancer (BTC) patients who are traditionally intolerant to chemotherapy. However, clinical evidence for single immunotherapy with pembrolizumab or nivolumab is limited. The present study assessed the safety and efficiency of the anti-PD-1 antibody, camrelizumab, as monotherapy in patients with unresectable or recurrent BTC. Methods: A retrospective evaluation was conducted among 4 patients with BTC, including 2 with intrahepatic cholangiocellular carcinoma (ICC), one with extrahepatic bile duct cancer, and one with gallbladder cancer. The patients with unresectable or recurrent BTC were refractory or intolerant to gemcitabine plus cisplatin treatment regimens and received at least one intravenous dose (3 mg/kg) of camrelizumab monotherapy every 3 weeks. Gene sequencing analysis was also performed for biomarker screening. Patient reaction was evaluated according to modified response evaluation criteria in solid tumor (RECIST) version 1.1, progression-free survival (PFS), and toxicity. Results: In this cohort, 1 patient with recurrent ICC had a positive response to treatment, with a substantial tumor size reduction in liver and lung metastases verified using a radiological test after receiving 3 cycles of camrelizumab. The PFS was 4.9 months. The remaining 3 patients showed no response to treatment and experienced disease progression. RNA sequence analysis didn’t found high expression on genes that related to PD-L1, microsatellite instability, tumor mutation burden, and DNA mismatch repair in these patients. Grade 3 treatment-related adverse event was observed in 1 patient. Conclusions: Anti-PD-1 antibody camrelizumab had a manageable safety profile in patients with advanced BTC. This initial assessment of camrelizumab monotherapy provides effective evidence for patients with refractory BTC in biomarker-unselected patients.

BackgroundOur previous study revealled amplified hazardous effects of macrosteatosis (MaS) on graft failure (GF) in recipients with severe liver damage in short post-operative days, with vague mechanism inside.AimWe aimed to uncover the molecular mechanism of donor MaS on GF, and construct the predictive model to monitor post-transplant prognosis based on “omics” perspective.MethodsUltra-performance liquid chromatography coupled to mass spectrometry metabolomic analysis was performed in allograft tissues from 82 patients with initial poor function (IPF) from multi-liver transplant (LT) centers. Pathway analysis was performed by on-line toolkit Metaboanalyst (v 3.0). Predictive model was constructed based on combinative metabonomic and clinical data extracted by stepwised cox proportional analysis.ResultsPrinciple component analysis (PCA) analysis revealled stratification on metabolic feature in organs classified by MaS status. Differential metabolits both associated with MaS and GF were significantly enriched on pathway of glycerophospholipid metabolism (P < 0.05). Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) involved in glycerophospholipid metabolism was significantly decreased in cases with MaS donors and GF (P < 0.05). Better prediction was observed on graft survival by combinative model (area under the curve = 0.91) and confirmed by internal validation.ConclusionMetabonomic features of allografts can be clearly distinguished by MaS status in patients with IPF. Dysfunction on glycerophospholipid metabolism was culprit to link donor MaS and final GF. Decrement on PC and PE exerted the fatal effects of MaS on organ failure. Metabonomic data might help for monitoring long-term graft survival after LT.

A novel strategy of dual steric hindrance, which was obtained by Janus modification of gold nanoparticles (Au NPs) and volume exclusion of DNA, was adopted to prepare mono-DNA-modified Au NPs. The yield of mono-DNA-functionalized Au NPs significantly improved from 44 to 70% in the reaction between Au NPs and thiolated DNA. Furthermore, the specificity of mono-DNA-functionalized Au NPs was enhanced from 57 to 95%. The as-prepared Au NPs without postsynthetic treatment showed good controllability in self-assembly fabrication of complex nanostructures. [ABSTRACT FROM AUTHOR]

Stereoselective total synthesis of natural product crisamicin A ( 1) was accomplished for the first time via the Pd/TMTU-catalyzed alkoxycarbonylative annulation to generate a unique cis-pyran-fused lactone, an intermolecular Diels−Alder reaction to construct the pyranonaphthoquinone unit, and a novel Pd−thiourea pincer complex-catalyzed homocoupling of functionalized naphthoquinones. [ABSTRACT FROM AUTHOR]

Abstract We performed integrative network analyses to identify targets that can be used for effectively treating liver diseases with minimal side effects. We first generated co‐expression networks (CNs) for 46 human tissues and liver cancer to explore the functional relationships between genes and examined the overlap between functional and physical interactions. Since increased de novo lipogenesis is a characteristic of nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC), we investigated the liver‐specific genes co‐expressed with fatty acid synthase (FASN). CN analyses predicted that inhibition of these liver‐specific genes decreases FASN expression. Experiments in human cancer cell lines, mouse liver samples, and primary human hepatocytes validated our predictions by demonstrating functional relationships between these liver genes, and showing that their inhibition decreases cell growth and liver fat content. In conclusion, we identified liver‐specific genes linked to NAFLD pathogenesis, such as pyruvate kinase liver and red blood cell (PKLR), or to HCC pathogenesis, such as PKLR, patatin‐like phospholipase domain containing 3 (PNPLA3), and proprotein convertase subtilisin/kexin type 9 (PCSK9), all of which are potential targets for drug development.

Background: Currently, 30% macrovesicular steatosis (MaS) content is usually assigned empirically as the boundary between “use” and “refuse” a donor liver for liver transplantation (LT); however, this cut-off is questionable due to the lack of systemic evidence of the efficiency relative to prognosis prediction. Clinicians have tried to identify the threshold for optimized utilization of marginal steatotic allografts, but controversy exists among different studies.Aim: Our study aimed to systematically determine an acceptable donor MaS content cut-off without incurring extra risk in liver transplantation, using meta-analysis.Methods: The relevant literature reporting the relationship between MaS content and post-transplant mortality/morbidity was searched and retrieved in Pubmed, Embase, and ISI Web of Science.Results: Nine studies were enrolled into the final analysis. A categorical comparison revealed that patients who received allografts with moderate steatosis (MaS content >30%) had significantly higher risks of graft failure/dysfunction, but not of mortality. Dose-response analysis showed that donor MaS content affected the graft failure/dysfunction in a non-linear relationship. Risks associated with MaS content in terms of poorer outcomes were independent of other risk covariates for liver transplantation. A non-significant increase in risk of inferior post-transplant outcomes was observed in patients who received allografts with a MaS content

Background/Aims: Hepatocellular carcinoma (HCC) is a lethal disease with nearly equal morbidity and mortality. Thus, the discovery and application of more useful predictive biomarkers for improving therapeutic effects and prediction of clinical outcomes is of crucial significance. Methods: A total of 475 HBV-related HCC patients were enrolled. Ataxin 7 (ATXN7) single nucleotide polymorphisms (SNPs) were genotyped by Sanger DNA sequencing after PCR amplification. The associations between ATXN7 SNPs and mRNA expression with the prognosis of HBV-related HCC were analyzed. Results: In all, rs3774729 was significantly associated with overall survival (OS) of HBV-related HCC (P = 0.013, HR = 0.66, 95% CI: 0.48-0.94). And patients with the AA genotype and a high level of serum alpha fetoprotein (AFP) had significantly worse OS when compared to patients with AG/GG genotypes and a low level of AFP (adjusted P = 0.007, adjusted HR = 1.83, 95% CI = 1.18-2.82). Furthermore, low expression of ATXN7 was significantly associated with poor recurrence-free survival (RFS) and OS (P = 0.007, HR = 2.38, 95% CI = 1.27-4.45 and P = 0.025, HR = 1.75, 95% CI = 1.18-2.62). Conclusion: ATXN7 may be a potential predictor of post-operative prognosis of HBV-related HCC.

Surpervoxels are becoming increasingly popular in many point cloud processing applications. However, few methods have been devised specifically for generating compact supervoxels from unstructured three-dimensional (3D) point clouds. In this study, we aimed to generate high quality over-segmentation of point clouds. We propose a merge-swap optimization framework that solves any supervoxel generation problem formulated in energy minimization. In particular, we tailored an energy function that explicitly encourages regular and compact supervoxels with adaptive size control considering local geometric information of point clouds. We also provide two acceleration techniques to reduce the computational overhead. The performance of the proposed merge-swap optimization approach is superior to that of previous work in terms of thorough optimization, computational efficiency, and practical applicability to incorporating control of other properties of supervoxels. The experiments show that our approach produces supervoxels with better segmentation quality than two state-of-the-art methods on three public datasets.

Previous studies revealed the potential significance of circulating adiponectin levels with respect to the diagnosis and prediction of metabolic syndrome, but uncertainty has been noted across different cohorts. Systematic evaluation was performed for diagnostic accuracy and predictivity of adiponectin variation for metabolic syndrome in enrolled studies including 1,248 and 6,020 subjects, respectively. Adiponectin can identify metabolic syndrome with moderate accuracy (area under the curve = 0.81, 95% CI: 0.77–0.84). Heterogeneity analysis revealed that an increasing index of insulin resistance was independently associated with improving the performance of adiponectin upon metabolic syndrome diagnosis (ratio of diagnostic odds ratio = 3.89, 95% CI: 1.13–13.9). In addition, reductions in adiponectin were associated with increasing metabolic syndrome incidence in a linear dose-response manner. The risk of hypoadiponectinemia with metabolic syndrome was especially increased in men (P < 0.05). Further Mendelian randomization analysis identified that the amplified risk could be attributed to increased susceptibility (up to 7%) to insulin resistance compared with women. In conclusion, adiponectin measurement might have potential benefits in the detection of metabolic syndrome. Factors that affect insulin resistance should be considered for adjustment in future assessments.

The release of a Cys probe from the cavity of a water-soluble pillar[5]arene can be realized in an acidic microenvironment. [ABSTRACT FROM AUTHOR]

A pillar[5]arene with mono(ethylene oxide) substituents could form a highly stable [2]pseudorotaxane with a rigid guest both in solution and in the solid state. [ABSTRACT FROM AUTHOR]

The bioavailability and toxicity of metals to aquatic organisms are highly dependent on water quality parameters in freshwaters. The biotic ligand model (BLM) for copper is an approach to generate the water quality criteria (WQC) with water chemistry in the ambient environment. However, few studies were carried out on the WQCs for copper based on the BLM approach in China. In the present study, the toxicity for copper to native Chinese aquatic organisms was conducted and the published toxicity data with water quality parameters to Chinese aquatic species were collected to derive the WQCs for copper by the BLM approach. The BLM-based WQCs (the criterion maximum criteria (CMC) and the criterion continuous concentration (CCC)) for copper in the freshwater for the nation and in the Taihu Lake were obtained. The CMC and CCC values for copper in China were derived to be 1.391 μg/L and 0.495 μg/L, respectively, and the CMC and CCC in the Taihu Lake were 32.194 μg/L and 9.697 μg/L. The high concentration of dissolved organic carbon might be a main reason which resulted in the higher WQC values in the Taihu Lake. The WQC of copper in the freshwater would provide a scientific foundation for water quality standards and the environment risk assessment in China.

OBJECTIVE: Controversy exists in using alanine aminotransferase (ALT) activity for predicting long-term survival. Therefore, this research study investigated the association between ALT activity and mortality through a systematic review and meta-analysis of previous prospective studies. METHODS: Electronic literature databases, including PubMed, Embase, and the Institute for Scientific Information (ISI), were searched for relevant prospective observational studies (published before Dec 30, 2013) on the association between baseline ALT activity and ensuing all-cause/disease-specific mortality. Information on nationality, sample size, participant characteristics, follow-up duration, comparison, outcome assessment, hazard ratios (HRs) and adjusted covariates was extracted. Pooled HRs and corresponding 95% confidence intervals (CIs) were separately calculated for categorical risk estimates (highest vs. lowest ALT categories) and continuous risk estimates (per 5 U/l of ALT increment) in subgroups separated by age (