Immunotherapy of microsatellite stable colorectal cancer: resistance mechanisms and treatment strategies.

In recent years, immunotherapy strategies based on immune checkpoint inhibitors have yielded good efficacy in colorectal cancer (CRC)especially in colorectal cancer with microsatellite instability-high. However, microsatellite-stable (MSS) CRCs account for about 85% of CRCs and are resistant to immunotherapy. Previous studies have shown that compared with MSS CRC, high microsatellite instability CRC possesses a higher frequency of mutations and can generate more neoantigens. Therefore, improving the sensitivity of immunotherapy to MSS CRC is a hot topic which is crucial for the treatment of MSS CRC. This review aims to discuss the factors contributing to MSS CRC insensitivity to immunotherapy and explored potential solutions to overcome immunotherapy resistance.

Two-Dimensional Nonbenzenoid Heteroacene Crystals Synthesized via In-Situ Embedding of Ladder Bipyrazinylenes on Au(111).

Precisely introducing topological defects is an important strategy in nanographene crystal engineering because defects can tune π-electronic structures and control molecular assemblies. The synergistic control of the synthesis and assembly of nanographenes by embedding the topological defects to afford two-dimensional (2D) crystals on surfaces is still a great challenge. By in-situ embedding ladder bipyrazinylene (LBPy) into acene, the narrowest nanographene with zigzag edges, we have achieved the precise preparation of 2D nonbenzenoid heteroacene crystals on Au(111). Through intramolecular electrocyclization of o-diisocyanides and Au adatom-directed [2+2] cycloaddition, the nonbenzenoid heteroacene products are produced with high chemoselectivity, and lead to the molecular 2D assembly via LBPy-derived interlocking hydrogen bonds. Using bond-resolved scanning tunneling microscopy, we determined the atomic structures of the nonbenzenoid heteroacene product and diverse organometallic intermediates. The tunneling spectroscopy measurements revealed the electronic structure of the nonbenzenoid heteroacene, which is supported by density functional theory (DFT) calculations. The observed distinct organometallic intermediates during progression annealing combined with DFT calculations demonstrated that LBPy formation proceeds via electrocyclization of o-diisocyanides, trapping of heteroarynes by Au adatoms, and stepwise elimination of Au adatoms.

Risk on assessment of 15 REEs and mixtures by DGT in Songhua River system sediments of China's largest old industrial base.

Rare earth elements (REEs) are increasingly used in the high-tech sectors in the world and are therefore called burgeoning contaminants. As diffusive gradients in thin films (DGT) can be used to assess the bioavailability of inorganic matters, in this paper, we evaluated, for the first time, the ecotoxicology risks of REEs and their mixtures in river sediments of China's old industrial base by DGT. During our research, taking the Songhua River system (SRS) as an example, we detected its surficial sediments, of which the DGT-labile concentration of REEs (∑REEs) was 2.07-8.76 µg/L. As for the single toxicity, the risk quotient (RQ) values of Y at all sites were significantly greater than 1; while the values of Nd and Pr in some upstream reaches were all significantly greater than the threshold (1), indicating that these adverse effects of single REEs were not neglected. In terms of the combined toxicity of REEs mixtures, we carried out an assessment of the risks of probabilistic ecotoxicology, which showed that the SRS superficial sediments had a low probability of toxicity to aquatic organisms (0.54%).

Advances and challenges in the prevention and treatment of COVID-19.

Since the end of 2019, a new type of coronavirus pneumonia (COVID-19) caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has been spreading rapidly throughout the world. Previously, there were two outbreaks of severe coronavirus caused by different coronaviruses worldwide, namely Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). This article introduced the origin, virological characteristics and epidemiological overview of SARS-CoV-2, reviewed the currently known drugs that may prevent and treat coronavirus, explained the characteristics of the new coronavirus and provided novel information for the prevention and treatment of COVID-19.

Distribution, Multi-Index Assessment, and Sources of Heavy Metals in Surface Sediments of Zhelin Bay, a Typical Mariculture Area in Southern China.

The occurrence, multi-index assessment, and sources of heavy metals in surface sediments of Zhelin Bay were investigated. Average heavy metal concentrations (mg/kg) were 81.89 (Cr), 770.76 (Mn), 16.81 (Co), 62.25 (Ni), 96.30 (Cu), 162.04 (Zn), and 73.40 (Pb), with the concentrations of studied seven heavy metals being significantly higher than their corresponding background values. Geo-accumulation index (Igeo) and pollution load index (PLI) were implemented to assess degree of heavy metal contamination. The Igeo and PLI indicated that Cr, Mn, Co, Zn, and Pb were slightly polluted, and Cu and Ni were moderately polluted in the region. Potential ecological risk index (RI) and mean possible effect level (PEL) quotient were conducted to assess ecological risk. The RI and mean PEL quotient demonstrated that surface sediments of Zhelin Bay were slight ecological risks and exhibited a 21% probability of toxicity. Principal component analysis (PCA) combined with the correlation analysis (CA) and hierarchical cluster analysis (HAC) revealed that the heavy metal contamination in Zhelin Bay might originate from three type sources.

Multi-index assessment of heavy metal contamination in surface sediments of the Pearl River estuary intertidal zone.

Surface sediments from 21 stations within the Pearl River estuary (PRE) intertidal zone were sampled for heavy metal contamination analysis. Average heavy metal concentrations (mg/kg) in the PRE intertidal zone were 118.5 (Cr), 860.4 (Mn), 19.5 (Co), 72.5 (Ni), 128.1 (Cu), 198.5 (Zn), and 73.0 (Pb), with the concentrations of Mn, Co, Ni, Cu, and Zn being significantly higher than their corresponding background values. The enrichment factor (EF) and geo-accumulation index (Igeo) reveal the same contamination status, with Pb, Ni, Co, Mn, and Cu showing slight to moderate contamination. Overall, the combined heavy metal concentration in the PRE intertidal surface sediments had a 24.7 % probability of toxic effects on aquatic biota based on the joint probabilistic risk (JPR) approach. Principal component analysis (PCA) coupled with the correlation analysis (CA) revealed that the heavy metal contamination in the PRE intertidal zone might originate from natural and anthropogenic sources.