A generalizable framework to comprehensively predict epigenome, chromatin organization, and transcriptome.

Many deep learning approaches have been proposed to predict epigenetic profiles, chromatin organization, and transcription activity. While these approaches achieve satisfactory performance in predicting one modality from another, the learned representations are not generalizable across predictive tasks or across cell types. In this paper, we propose a deep learning approach named EPCOT which employs a pre-training and fine-tuning framework, and is able to accurately and comprehensively predict multiple modalities including epigenome, chromatin organization, transcriptome, and enhancer activity for new cell types, by only requiring cell-type specific chromatin accessibility profiles. Many of these predicted modalities, such as Micro-C and ChIA-PET, are quite expensive to get in practice, and the in silico prediction from EPCOT should be quite helpful. Furthermore, this pre-training and fine-tuning framework allows EPCOT to identify generic representations generalizable across different predictive tasks. Interpreting EPCOT models also provides biological insights including mapping between different genomic modalities, identifying TF sequence binding patterns, and analyzing cell-type specific TF impacts on enhancer activity.

Dual active sites over Cu-ZnO-ZrO2 catalysts for carbon dioxide hydrogenation to methanol.

CO2 hydrogenation to methanol is a significant approach to tackle the problem of global warming and simultaneously meet the demand for the portable fuel. Cu-ZnO catalysts with various kinds of promoters have received wide attention. However, the role of promoter and the form of active sites in CO2 hydrogenation are still in debate. Here, various molar ratios of ZrO2 were added into the Cu-ZnO catalysts to tune the distributions of Cu0 and Cu+ species. A volcano-like trend between the ratio of Cu+/ (Cu+ + Cu0) and the amount of ZrO2 is presented, among which the CuZn10Zr (the molar ratio of ZrO2 is 10%) catalyst reaches the highest value. Correspondingly, the maximum value of space-time yield to methanol with 0.65 gMeOH/(gcat·hr) is obtained on CuZn10Zr at reaction conditions of 220°C and 3 MPa. Detailed characterizations demonstrate that dual active sites are proposed during CO2 hydrogenation over CuZn10Zr catalyst. The exposed Cu0 takes participate in the activation of H2, while on the Cu+ species, the intermediate of formate from the co-adsorption of CO2 and H2 prefers to be further hydrogenated to CH3OH than decomposing into the by-product of CO, yielding a high selectivity of methanol.

Neoadjuvant immunotherapy improves outcomes for resectable gastroesophageal junction cancer: A systematic review and meta-analysis.

BACKGROUND: In recent years, neoadjuvant immunotherapy (NAIT) has developed rapidly in patients with gastroesophageal junction cancer (GEJC). The suggested neoadjuvant treatment regimens for patients with GEJC may vary in light of the efficacy and safety results. METHODS: A search of the Cochrane Library, PubMed, Embase, and Web of Science was completed to locate studies examining the safety and effectiveness of NAIT for resectable GEJC. We analyzed the effect sizes (ES) and 95% confidence intervals (CI) in addition to subgroups and heterogeneity. Meta-analyses were performed using Stata BE17 software. RESULTS: For these meta-analyses, 753 patients were chosen from 21 studies. The effectiveness of NAIT was assessed using the pathological complete response (pCR), major pathological response (MPR), and nodal downstage to ypN0 rate. The MPR, pCR, and nodal downstage to ypN0 rate values in NAIT were noticeably higher (MPR: ES = 0.45; 95% CI: 0.36-0.54; pCR: ES = 0.26; 95% CI: 0.21-0.32; nodal downstage to ypN0 rate: ES = 0.60; 95% CI: 0.48-0.72) than those of neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) (MPR < 30%; pCR: ES = 3%-17%; nodal downstage to ypN0 rate: ES = 21%-29%). Safety was assessed using the treatment-related adverse events (trAEs) incidence rate, surgical delay rate, surgical complications incidence rate, and surgical resection rate. In conclusion, the incidence of trAEs, incidence of surgical complications, and surgical delay rate had ES values of 0.66, 0.48, and 0.09, respectively. These rates were comparable to those from nCT or nCRT (95% CI: 0.60-0.70; 0.15-0.51; and 0, respectively). The reported resection rates of 85%-95% with nCT or nCRT were comparable to the mean surgical resection rate of 90%. CONCLUSION: NAIT is an effective treatment for resectable GEJC; additionally, the level of NAIT toxicity is acceptable. The long-term effects of NAIT require further study.

Efficient electrotransformation of Rhodococcus ruber YYL with abundant extracellular polymeric substances via a cell wall-weakening strategy.

Rhodococcus spp. have broad potential applications related to the degradation of organic contaminants and the transformation or synthesis of useful compounds. However, some Gram-positive bacteria are difficult to manipulate genetically due to low transformation efficiency. In this study, we investigated the effects of chemicals including glycine, isonicotinic acid hydrazide (INH), Tween 80 and penicillin G, as well as cell growth status, competent cell concentration, electroporation field strength, electroporation time and heat shock time, on the electrotransformation efficiency of the tetrahydrofuran-degrading bacterium Rhodococcus ruber YYL with low transformation efficiency. The highest electrotransformation efficiency was 1.60 × 106 CFU/µg DNA after parameter optimization. GmhD (D-glycero-D-manno-heptose 1-phosphate guanosyltransferase) gene, which is important in the biosynthesis of lipopolysaccharide, was deleted via the optimized electrotransformation method. Compared with wild-type strain, YYL ΔgmhD showed extremely high electrotransformation efficiency because the surface of it had no mushroom-like extracellular polymeric substances (EPS). In addition, the results showed that cell wall-weakening reagents might cause some translucent substances like EPS, to detach from the cells, increasing the electrotransformation efficiency of strain YYL. We propose that these results could provide a new strategy for unique bacteria that are rich in EPS, for which genetic manipulation systems are difficult to establish.

Generalized reactivity descriptor of defective carbon catalysts for acetylene hydrochlorination: the ratio of sp2 : sp3 hybridization.

The golden section point in carbon catalysts for acetylene hydrochlorination has been determined. The surface sp2 : sp3 ratio of two types of carbon catalysts, including nanodiamond- and graphite-oriented carbons, both have a volcano relationship with the catalytic performance for acetylene hydrochlorination, and the optimized ratios are both around 32-35%.

Thiamine-Mediated Cooperation Between Auxotrophic Rhodococcus ruber ZM07 and Escherichia coli K12 Drives Efficient Tetrahydrofuran Degradation.

Tetrahydrofuran (THF) is a universal solvent widely used in the synthesis of chemicals and pharmaceuticals. As a refractory organic contaminant, it can only be degraded by a small group of microbes. In this study, a thiamine auxotrophic THF-degrading bacterium, Rhodococcus ruber ZM07, was isolated from an enrichment culture H-1. It was cocultured with Escherichia coli K12 (which cannot degrade THF but can produce thiamine) and/or Escherichia coli K12ΔthiE (which can neither degrade THF nor produce thiamine) with or without exogenous thiamine. This study aims to understand the interaction mechanisms between ZM07 and K12. We found that K12 accounted for 30% of the total when cocultured and transferred with ZM07 in thiamine-free systems; in addition, in the three-strain (ZM07, K12, and K12ΔthiE) cocultured system without thiamine, K12ΔthiE disappeared in the 8th transfer, while K12 could still stably exist (the relative abundance remained at approximately 30%). The growth of K12 was significantly inhibited in the thiamine-rich system. Its proportion was almost below 4% after the fourth transfer in both the two-strain (ZM07 and K12) and three-strain (ZM07, K12, and K12ΔthiE) systems; K12ΔthiE's percentage was higher than K12's in the three-strain (ZM07, K12, and K12ΔthiE) cocultured system with exogenous thiamine, and both represented only a small proportion (less than 1% by the fourth transfer). The results of the coculture of K12 and K12ΔthiE in thiamine-free medium indicated that intraspecific competition between them may be one of the main reasons for the extinction of K12ΔthiE in the three-strain (ZM07, K12, and K12ΔthiE) system without exogenous thiamine. Furthermore, we found that ZM07 could cooperate with K12 through extracellular metabolites exchanges without physical contact. This study provides novel insight into how microbes cooperate and compete with one another during THF degradation.

Defective graphene@diamond hybrid nanocarbon material as an effective and stable metal-free catalyst for acetylene hydrochlorination.

A defective nanodiamond-graphene material (ND@G) exhibits superior catalytic activity in acetylene hydrochlorination with an acetylene conversion of 50%, selectivity to vinyl chloride of up to 99.5% at 220 °C, and a C2H2 gas hourly space velocity of 300 h-1, which is the first example of a metal-free catalyst with comparable performance to that of the 0.25% Au/C catalyst.

Wheat flour-derived N-doped mesoporous carbon extrudate as superior metal-free catalysts for acetylene hydrochlorination.

N-Doped mesoporous carbon extrudate with a major quaternary N species has been successfully prepared through direct carbonization of wheat flour/gluten with silica, which is a cheap and convenient method for scale-up production approach. The obtained carbon extrudate metal-free catalyst enables highly efficient production of vinyl chloride monomer through acetylene hydrochlorination, with a superior catalytic performance and excellent stability (>85% conversion and vinyl chloride selectivity over 99% at 220 °C).