Thorough investigations using Raman spectra of solid methane (CH4) were conducted using moissanite anvil cells in the range of 1−43 GPa at room temperature to identify high-pressure phases. Two novel phases that are distinguishable from previously reported phases were uncovered. One, with a narrow pressure range of 1 GPa centered at around 12.5 GPa and another, with a range of 3 GPa centered around 40.5 GPa. Our results do not support the existence of a phase transformation around 25 GPa. The high quality Raman spectra, obtained by using single crystal samples, narrow the boundaries of seven methane phases at pressures up to 43.2 GPa.
Recent studies on water retention behaviour of biochar amended soil rarely considers the effect of pyrolysis temperature and also feedstock type into account. It is well known that pyrolysis temperature and feedstock type influences the physical and chemical properties of biochar due to stagewise decomposition of structure and chemical bonds. Further, soil density, which is in a loose state (in agricultural applications) and dense (in geo-environmental engineering applications) can also influence water retention behaviour of biochar amended soils. The major objective of this study is to investigate the water retention properties of soil amended with three different biochars in both loose and dense state. The biochars, i.e. water hyacinth biochar (WHB), chicken manure biochar (CMB) and wood biochar (WB) were produced in-house at different pyrolysis temperature. After then, biochars at 5% and 10% (w/w%) were amended to the soil. Water retention behaviour (soil suction and gravimetric water content) was studied under drying and wetting cycle simulated by varying relative humidity (RH, 50–90%). Results show that 10% WHB produced at 300 °C were found to possess highest water retention. CMB is found to possess higher water retention than WB for 10% amendment ratio. In general, the addition of three biochars (at both 300 °C and 600 °C) at 10% (w/w) significantly improved the water retention at all suction ranges in both loose and dense compaction state as compared to that of the bare soil. The adsorption (wetting) and desorption (drying) capacity of biochar amended soils is constant at corresponding RH.
Background: Neoadjuvant chemotherapy (NAC) and neoadjuvant chemoradiotherapy (NACR) are the standard treatments for esophageal squamous cell carcinoma (ESCC). However, the 5-year overall survival (OS) rate is still far from satisfactory. In recent years, immune checkpoint inhibitors (ICIs) have shown promising results in the treatment of ESCC. More than 20 phase II clinical trials have been launched to explore combinations of ICIs in the neoadjuvant setting for ESCC. Based on our phase II clinical trial, a two-arm phase III trial was launched in Henan Cancer Hospital. ICIs combined with NAC may usher in a new era and may benefit locally advanced, resectable ESCC patients.Methods: A two-arm phase III trial was launched in April 2020 in Henan Cancer Hospital. Patient recruitment will be completed within 18 months. The primary endpoint is event-free survival (EFS).The secondary endpoints include pathologic complete response (pCR), disease-free survival (DFS) rate, overall response rate (ORR), R0 resection rate, major pathologic response (MPR), adverse events (AEs), complication rate and quality of life (QOL). A biobank of pretreatment, resected tumor tissue and paired blood samples will be built for translational research in the future.Discussion: This RCT directly compares NAC with neoadjuvant toripalimab plus chemotherapy in terms of EFS for locally advanced ESCC. The results may usher in a new era of resectable ESCC treatment.
Esophageal squamous cell carcinoma (ESCC) occurs with highest frequency in China with over 90% mortality, highlighting the need for early detection and improved treatment strategies. We aimed to identify ESCC cancer predisposition gene(s). Our study included 4,517 individuals. The discovery phase using whole‐exome sequencing (WES) included 186 familial ESCC patients from high‐risk China. Targeted gene sequencing validation of 598 genes included 3,289 Henan and 1,228 moderate‐risk Hong Kong Chinese. A WES approach identified BRCA2 loss‐of‐function (LOF) mutations in 3.23% (6/186) familial ESCC patients compared to 0.21% (9/4300) in the ExAC East Asians (odds ratio [OR] = 15.89, p = 2.48 × 10−10). BRCA2 LOF mutation frequency in the combined Henan cohort has significantly higher prevalence (OR = 10.55, p = 0.0035). Results were independently validated in an ESCC Hong Kong cohort (OR = 10.64, p = 0.022). One Hong Kong pedigree was identified to carry a BRCA2 LOF mutation. BRCA2 inactivation in ESCC was via germline LOF mutations and wild‐type somatic allelic loss via loss of heterozygosity. Gene‐based association analysis, including LOF mutations and rare deleterious missense variants defined with combined annotation dependent depletion score ≥30, confirmed the genetic predisposition role of BRCA2 (OR = 9.50, p = 3.44 × 10−5), and provided new evidence for potential association of ESCC risk with DNA repair genes (POLQ and MSH2), inflammation (TTC39B) and angiogenesis (KDR). Our findings are the first to provide compelling evidence of the role of BRCA2 in ESCC genetic susceptibility in Chinese, suggesting defective homologous recombination is an underlying cause in ESCC pathogenesis, which is amenable to therapeutic options based on synthetic lethality approaches such as targeting BRCA2 with PARP1 inhibitors in ESCC.
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