Metastasis-related recurrence often occurs in hepatocellular carcinoma (HCC) patients who receive curative therapies. At present, it is challenging to identify patients with high risk of recurrence, ...which would warrant additional therapies. In this study, we sought to analyze a recently developed metastasis-related gene signature for its utility in predicting HCC survival, using 2 independent cohorts consisting of a total of 386 patients who received radical resection. Cohort 1 contained 247 predominantly HBV-positive cases analyzed with an Affymetrix platform, whereas cohort 2 contained 139 cases with mixed etiology analyzed with the NCI Oligo Set microarray platform. We employed a survival risk prediction algorithm with training, test, and independent cross-validation strategies and found that the gene signature is predictive of overall and disease-free survival. Importantly, risk was significantly predicted independently of clinical characteristics and microarray platform. In addition, survival prediction was successful in patients with early disease, such as small (<5 cm in diameter) and solitary tumors, and the signature predicted particularly well for early recurrence risk (<2 years), especially when combined with serum alpha fetoprotein or tumor staging. In conclusion, we have shown in 2 independent cohorts with mixed etiologies and ethnicity that the metastasis gene signature is a useful tool to predict HCC outcome, suggesting the general utility of this classifier. We recommend the use of this classifier as a molecular diagnostic test to assess the risk that an HCC patient will develop tumor relapse within 2 years after surgical resection, particularly for those with early-stage tumors and solitary presentation.
Ni-based composite coatings reinforced by TiBX/TiXNiY/TiC with different Ti6Al4V contents were precipitated on a 35CrMoV substrate via laser cladding. The phase composition, elemental distribution, ...and precipitated phases of the coatings were characterised using X-ray diffraction, energy dispersive X-ray spectroscopy, scanning electron microscopy, and transmission electron microscopy. The mechanical and tribological properties of the cladding layer were also characterised. The results showed that the coating contained TiB2, TiC, TiB, Ni3Ti, and NiTi2 phases with uniform elemental distribution and grain refinement. A schematic of the growth model and precipitation sequence of the reinforced phases was generated. The microstructure, elemental segregation, hardness, and friction behaviour of the cladding layer were significantly influenced by the addition of Ti6Al4V. The optimal microstructure and best mechanical properties were obtained by the addition of 4 wt% Ti6Al4V, with that coating possessing a hardness, average friction coefficient, and wear volume of 770.8 HV1, 0.180 and 6132 um3, respectively.
Designing bifunctional oxygen electrocatalysts with high activity, lasting stability, and low-cost for rechargeable zinc-air batteries (RZABs) is a tough challenge. Herein, an advanced ...electrocatalyst is prepared by anchoring atomically dispersed Co atoms on N-doped graphene-like hierarchically porous carbon nanosheets (SA-Co-N
4
-GCs) and thereby forming Co-N
4
-C architecture. Its unique structure with excellent conductivity, large surface area, and three dimensional (3D) interconnected hierarchically porous architecture exposes not only more Co-N
4
active sites to accelerate the kinetics of both oxygen reduction reaction (ORR) and oxygen evolution reaction (OER), but also provides an efficient charge/mass transport environment to reduce diffusion barrier. Consequently, SA-Co-N
4
-GCs exhibits excellent ORR/OER bifunctional activities and durability, surpassing noble-metal catalysts. Liquid RZABs using SA-Co-N
4
-GCs cathodes display a high open-circuit voltage of 1.51 V, a remarkable power density of 149.3 mW·cm
−2
, as well as excellent stability and rechargeability with faint increase in polarization even at a large depth of charge—discharge cycle with 16 h per cycle over an entire 600 h long-term test. Moreover, flexible quasi-solid-state RZABs with SA-Co-N
4
-GCs cathodes also deliver a considerable power density of 124.5 mW·cm
−2
, which is even higher than that of liquid batteries using noble-metal catalysts. This work has thrown new insight into development of high-performance and low-cost electrocatalysts for energy conversion and storage.
A novel method for the glycosylation of selenoglycosides activated by iodosylbenzene was developed. The glycosylation reaction conditions were mild, fast, and efficient, with a high tolerance to ...diverse protecting groups and a wide substrate scope, which is advantageous for synthesizing complex glycosides. In addition, selenoglycosides were shown to be orthogonal to thioglycosides under the promotion of iodosylbenzene. Notably, a high yield of the poorly reactive glucuronidation reaction product was obtained by acetyl-protected selenoglycoside. Finally, the orthogonal one-pot synthesis of β-(1→6) oligoglucans demonstrated the usefulness of this method in oligosaccharide synthesis.
A series of derivatives of salidroside with mirror isomer glucose and different phenyl moieties were synthesized by Schmidt glycosylation in satisfactory yields, and their antioxidant and ...anti-inflammatory activities were evaluated by using LPS-induced RAW264.7 cells. One of the synthesized derivatives ʟ-Sal-4, bearing ʟ-glycosyl and -OMe modification at the phenyl ring, exhibited high activity in inhibiting the production of pro-inflammatory cytokines and oxidative stress biomarker MDA as well as in enhancing the activity of SOD enzyme, compared with the natural product and its corresponding ᴅ-enantiomer. Further proteomic analysis suggested that ʟ-Sal-4 exerted its anti-inflammatory activity through metabolic reprogramming. The in vitro activity showed that ʟ-Sal-4 is a potent antioxidant and anti-inflammatory agent. Our finding indicated that the ʟ-glucose-derived salidroside might be a promising lead compound in the development of salidroside derivatives as therapeutic agents.
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•A series of derivatives of salidroside with mirror isomer glucose were synthesized.•ʟ-Sal-4 exhibited high activity in both anti-inflammatory and antioxidant assays.•ʟ-Sal-4 exerted its anti-inflammatory activity through metabolic reprogramming.
3‐Deoxy‐d‐manno‐oct‐2‐ulosonic acid (Kdo) is an eight‐carbon monosaccharide found widely in bacterial lipopolysaccharides (LPSs) and capsule polysaccharides (CPSs). We developed an indirect method ...for the stereoselective synthesis of α‐Kdo glycosides with a C3‐p‐tolylthio‐substituted Kdo phosphite donor. The presence of the p‐tolylthio group enhanced the reactivity, suppressed the formation of elimination by‐products (2,3‐enes), and provided complete α‐stereocontrol. A variety of Kdo α‐glycosides were synthesized by our method in excellent yields (up to 98 %). After glycosylation, the p‐tolylthio group can be efficiently removed by free‐radical reduction. Subsequently, the orthogonality of the phosphite donor and thioglycoside donor was demonstrated by the one‐pot synthesis of a trisaccharide in Helicobacter pylori and Neisseria meningitidis LPS. Moreover, an efficient total synthesis route to the challenging 4,5‐branched Kdo trisaccharide in LPSs from several A. baumannii strains was highlighted. To demonstrate the high reactivity of our approach further, the highly crowded 4,5,7,8‐branched Kdo pentasaccharide was synthesized as a model molecule for the first time. Additionally, the reaction mechanism was investigated by DFT calculations.
A modified donor has been developed for the glycosylation of 3‐deoxy‐d‐manno‐2‐octulosonic acid (Kdo). The high reactivity and wide substrate scope of the donor enabled the synthesis of a range of Kdo‐containing glycosides with complete α‐stereoselectivity without the formation of 2,3‐ene by‐products. Several natural oligosaccharides were synthesized by a stepwise or one‐pot process, including a highly branched Kdo pentasaccharide.
Ventricular septal defect (VSD), one of the most common types of congenital heart disease (CHD), results from a combination of environmental and genetic factors. Recent studies demonstrated that ...microRNAs (miRNAs) are involved in development of CHD. This study was to characterize the expression of miRNAs that might be involved in the development or reflect the consequences of VSD.
MiRNA microarray analysis and reverse transcription-polymerase chain reaction (RT-PCR) were employed to determine the miRNA expression profile from 3 patients with VSD and 3 VSD-free controls. 3 target gene databases were employed to predict the target genes of differentially expressed miRNAs. miRNAs that were generally consensus across the three databases were selected and then independently validated using real time PCR in plasma samples from 20 VSD patients and 15 VSD-free controls. Target genes of validated 8 miRNAs were predicted using bioinformatic methods.
36 differentially expressed miRNAs were found in the patients with VSD and the VSD-free controls. Compared with VSD-free controls, expression of 15 miRNAs were up-regulated and 21 miRNAs were downregulated in the VSD group. 15 miRNAs were selected based on database analysis results and expression levels of 8 miRNAs were validated. The results of the real time PCR were consistent with those of the microarray analysis. Gene ontology analysis indicated that the top target genes were mainly related to cardiac right ventricle morphogenesis. NOTCH1, HAND1, ZFPM2, and GATA3 were predicted as targets of hsa-let-7e-5p, hsa-miR-222-3p and hsa-miR-433.
We report for the first time the circulating miRNA profile for patients with VSD and showed that 7 miRNAs were downregulated and 1 upregulated when matched to VSD-free controls. Analysis revealed target genes involved in cardiac development were probably regulated by these miRNAs.
Esophageal cancer (EC) is an aggressive neoplasm of the gastrointestinal tract that is usually treated with a combination of chemotherapy, radiotherapy (RT), and/or surgery, according to disease ...status. Despite the availability of multimodal therapeutic strategies, local recurrence is frequently observed. However, there is no standard treatment or promising therapeutic approach for local recurrence or metastatic esophageal carcinoma after the RT. This study tended to investigate the efficacy and safety of sintilimab maintenance after concurrent chemoradiotherapy (CCRT) for local/regional recurrent esophageal squamous carcinoma.
This study was a single-arm, phase Ib/II trial conducted in a single site in China. Patients previously radically treated (surgery or CCRT), histologically confirmed, local or regional recurrence esophageal squamous carcinoma, qualified for the study design, were treated with 25-28 times radiotherapy plus raltitrexed once every 3 weeks for up to two cycles. Patients who have not progressed after CCRT received sintilimab as maintenance once every 3 weeks up to 1 year. Primary endpoints were overall survival (OS) and safety. Secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR).
Between September 2019 and March 2022, in a total of 36 enrolled patients, 34 pts completed CCRT. Three patients excluded due to violation of the exclusion criteria (1 pt) and consent withdrawal (2 pts). Finally, 33 pts were included in the final analysis, in which 3 pts had disease progression, and the remaining 30 entered maintenance therapy with sintilimab. The median follow-up time was 12.3 months. Median OS was 20.6 months (95%CI 10.5-NA) and the 1-year OS rate was 64%. Median PFS was 11.5 months (95%CI 5.29-21.3) and the 1-year PFS rate was 43.6%. The ORR was 63.6% (95%CI 44.6-77.8), including 2 cases of CR and 19 cases of PR. The DCR was 19.9%, the median DOR was 19.5 months, and the median TTR was 2.4 months. The rate of any grade TRAEs was 96.7%; ≥Grade 3 TRAE was 23.4%. The incidence of immune-related AE was 60%, most of which were grade 1-2, and only one case of thyroid-stimulating hormone increased was irAE with grade 3 or above.
Sintilimab has shown promising clinical efficacy and a manageable safety profile as maintenance therapy after CCRT for local/regional recurrent esophageal squamous carcinoma. In addition, further confirmation from a large-scale real-world study is still needed.
The purpose of the present study was to investigate risk factors for esophageal fistula (EF) in patients with recurrent esophageal cancer receiving re-radiotherapy with or without chemotherapy.
We ...reviewed retrospectively the clinical characters and dosimetric parameters of 96 patients with recurrent esophageal cancer treated with re-radiotherapy in Cancer Hospital Affiliated to Shandong First Medical University between August 2014 and January 2021.Univariate and multivariate logistic regression analyses were provided to determine the risk factors of EF induced by re-radiotherapy.
The median time interval between two radiotherapy was 23.35 months (range, 4.30 to 238.10 months). EF occurred in 19 patients (19.79%). In univariate analysis, age, T stage, the biologically equivalent dose in the re-radiotherapy, total biologically equivalent dose, hyperfractionated radiotherapy, ulcerative esophageal cancer, the length of tumor and the maximum thickness of tumor had a correlation with the prevalence of EF. In addition, age (HR = 0.170, 95%CI 0.030-0.951, p = 0.044), T stage (HR = 8.369, 95%CI 1.729-40.522, p = 0.008), ulcerative esophageal cancer (HR = 5.810, 95%CI 1.316-25.650, p = 0.020) and the maximum thickness of tumor (HR = 1.314, 95%CI 1.098-1.572, p = 0.003) were risk factors of EF in multivariate logistic regression analysis.
The incidence of EF was significantly increased in patients with recurrent esophageal cancer who underwent re-radiotherapy. This study revealed that age, T stage, ulcerative esophageal cancer and the maximum thickness of the tumor were risk factors associated with EF. In clinical work, patients with risk factors for EF ought to be highly concerned and individualized treatment plans should be taken to reduce the occurrence of EF.
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