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Despite neoadjuvant/conversion chemotherapy, the prognosis of cT4a/bN+ gastric cancer is poor. Immune checkpoint inhibitors (ICIs) and antiangiogenic agents have shown activity in late-stage gastric cancer, but their efficacy in the neoadjuvant/conversion setting is unclear. In this single-armed, phase II, exploratory trial (NCT03878472), we evaluate the efficacy of a combination of ICI (camrelizumab), antiangiogenesis (apatinib), and chemotherapy (S-1 ± oxaliplatin) for neoadjuvant/conversion treatment of cT4a/bN+ gastric cancer. The primary endpoints are pathological responses and their potential biomarkers. Secondary endpoints include safety, objective response, progression-free survival, and overall survival. Complete and major pathological response rates are 15.8% and 26.3%. Pathological responses correlate significantly with microsatellite instability status, PD-L1 expression, and tumor mutational burden. In addition, multi-omics examination reveals several putative biomarkers for pathological responses, including RREB1 and SSPO mutation, immune-related signatures, and a peripheral T cell expansion score. Multi-omics also demonstrates dynamic changes in dominant tumor subclones, immune microenvironments, and T cell receptor repertoires during neoadjuvant immunotherapy. The toxicity and post-surgery complications are limited. These data support further validation of ICI- and antiangiogenesis-based neoadjuvant/conversion therapy in large randomized trials and provide candidate biomarkers. Immune checkpoint inhibitors and antiangiogenic agents have shown some activity in patients with late-stage gastric cancer. Here the authors report the results of a phase II trial of neoadjuvant anti-PD1 (camrelizumab), antiangiogenic agent (apatinib), and chemotherapy (S-1 ± Oxaliplatin) in stage T4a/bN + M0 gastric cancer patients. [ABSTRACT FROM AUTHOR]

Background: Ankle-brachial index (ABI) is a simple, non-invasive and easy-to-obtain measure for the evaluation of atherosclerotic peripheral arterial disease (PAD). This study aimed to investigate the relationships between body fluid volumes, body composition, body fat distribution and ABI at a population perspective. Results: Using the US National Health and Nutrition Examination Survey Data (NHANES) during 1999–2000, 2001–2002, and 2003–2004, adults ≥ 40 years old were eligible for inclusion. Univariate and multivariable linear and logistic regression analyses were performed to determine the associations between ABI, body fluid volume and body composition assessed by bioelectrical impedance analysis (BIA), and body fat distribution assessed by dual-energy X-ray absorptiometry (DEXA). After exclusion, the final analytic sample contained 1535 participants who were representative of totally 28,572,458 subjects in the US. After adjustments for relevant confounders, estimated fat mass was significantly and inversely associated with ABI (beta: − 0.0009, 95% CI = − 0.0015, − 0.0003). Total percent fat (beta: − 0.0024, 95% CI = − 0.0033, − 0.0014), trunk percent fat (beta: − 0.0016, 95% CI = − 0.0023, − 0.0009), and percent fat at the four limbs were also significantly and inversely associated with ABI (p < 0.001). In addition, subjects with higher estimated fat mass, total percent fat, trunk percent fat and higher percent fat at the four limbs were all significantly more likely to have abnormal ABI < 0.9. No significant association between parameters of body fluid volume and abnormal ABI was observed. Conclusions: Estimated fat mass, total percent fat, trunk percent fat and percent fat at the four limbs were significantly and inversely associated with ABI. Subjects with abnormal ABI are more likely to have higher total percent fat, trunk percent fat and the limb fat. These findings fill the knowledge gap on the relationships between atherosclerosis and body fat distribution. Further well-designed prospective studies are needed to confirm the present findings. [ABSTRACT FROM AUTHOR]

Via the solvothermal reaction between Zn(II) or Mn(II) salts and 5-(3,4-dicarboxylphenoxy)nicotinic acid (H3L) ligand, a trifunctional N,O-building block having three diverse kinds of functional groups (O-ether, N-pyridyl and COOH), two new coordination polymers (CPs) could be generated, and their chemical formulae respectively are {[Mn3(L)2(H2O)2]·4H2O} (1) and {[Zn(HL)]·NMP} (2). The complex 2 based on Zn(II) possesses high efficiency of fluorescence quenching for the nitrophenol (2,4,6-trinitrophenol, TNP; 4-nitrophenol, 4-NP; 3-nitrophenol, 3-NP; 2-nitrophenol, 2-NP) in the aqueous solution. Furthermore, the treatment activity of compounds on the atherosclerosis was assessed, and relevant mechanism was investigated. First of all, the ELISA assay was used to measure the content of the inflammatory cytokines released into the plasma. Besides, the levels of the NF-κb signaling pathway in the vascular endothelial cells were measured with real time RT-PCR. The hemolysis test was conducted in this research to measure the biocompatibility of the new compound. [ABSTRACT FROM AUTHOR]

In this work, reduced graphene oxide decorated with well-distributed TiO2 nanoparticles is fabricated through one-step hydrothermal reaction to modify CNTs@S cathode as a barrier layer. Its three-dimensional interconnected layered structure can restrain the migration of polysulfides, as well as promote electrical and ionic conduction. The uniformly distributed TiO2 nanoparticles on reduced graphene oxide surface also anchor the lithium polysulfides through chemical interaction, which benefits the cycle stability of the sulfur-containing cathode. As a result, the sulfur-containing cathode with the barrier layer reaches an initial reversible specific capacity of 1090.4 mAh g−1 at 0.2C, with the capacity retention of 93.1% after 150 cycles and the coulombic efficiency above 99%. [ABSTRACT FROM AUTHOR]

A three-dimensional (3D) network structure Si/C anode with large pores is fabricated by using gelatin-PVA as carbon source. Silicon particles are embedded in the 3D network carbon skeleton. Gaussian calculation and FTIR test are employed to analyze the role of molecules interaction in forming the 3D network structure. The modified Si/C anode exhibits a reversible capacity of 830 mA h g after 100 cycles at 400 mA g, and a capacity of 810 mA h g at 1.6 A g and 521 mA h g at 3.2 A g. The 3D network structure with large pores benefits the electrolyte penetration, and the carbon coating layer avoids the direct contact of silicon particles with the electrolyte. The carbon layer can also help buffer the volume expansion of silicon, which is good to the cycling stability. All these aspects contribute to the enhanced electrochemical performance of the Si anode. [ABSTRACT FROM AUTHOR]

The liver and gallbladder are among the most important internal organs derived from the endoderm, yet the development of the liver and gallbladder in the early embryonic stages is not fully understood. Using a transgenic Foxa2eGFP reporter mouse line, we performed single-cell full-length mRNA sequencing on endodermal and hepatic cells isolated from ten embryonic stages, ranging from E7.5 to E15.5. We identified the embryonic liver developmental trajectory from gut endoderm to hepatoblasts and characterized the transcriptome of the hepatic lineage. More importantly, we identified liver primordium as the nascent hepatic progenitors with both gut and liver features and documented dynamic gene expression during the epithelial-hepatic transition (EHT) at the stage of liver specification during E9.5–11.5. We found six groups of genes switched on or off in the EHT process, including diverse transcripitional regulators that had not been previously known to be expressed during EHT. Moreover, we identified and revealed transcriptional profiling of gallbladder primordium at E9.5. The present data provides a high-resolution resource and critical insights for understanding the liver and gallbladder development. The authors report a single cell-resolution gene expression atlas for the developing mouse liver and gallbladder using a transgenic Foxa2eGFP mouse line. By tracing the development of cells from gut endoderm to hepatoblasts they identify key transcriptional changes during liver specification. [ABSTRACT FROM AUTHOR]