Gustative Roussy Immune Score is a Predictor for Major Pathological Response in Rectal Cancer: A Result from the Preoperative Intraarterial Chemoembolization Combined with Radiotherapy (PCAR) Study.

Despite the emergence of various treatment strategies for rectal cancer based on neoadjuvant chemoradiotherapy, there is currently a lack of reliable biomarkers to determine which patients will respond well to neoadjuvant chemoradiotherapy. Through collecting hematological and biochemical parameters data of patients prior to receiving neoadjuvant chemoradiotherapy, we evaluated the predictive value of systemic inflammatory indices for pathological response and prognosis in rectal cancer patients. We found that baseline GRIm-Score was an independent predictor for MPR in rectal cancer patients. However, no association was observed between several commonly systemic inflammation indices and long-term outcome.

Negative prognostic impact of Co-mutations in TGFß and TP53 pathways in surgically resected rectal tumors following neoadjuvant chemoradiotherapy.

BACKGROUND: Preoperative neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) is a common approach for treating patients with locally advanced rectal cancer. Nevertheless, the mutational profile and its prognostic impact in surgically resected tumor specimens after nCRT remains to be clarified. METHODS: The comprehensive analysis of mutational landscape was retrospectively conducted by target regions sequencing approach that covered 150 tumor-related genes. Univariate and multivariate logistic regression and Cox regression was used to examine the association of mutation status in genes and pathways with pathological response and prognosis. Data from Memorial Sloan Kettering Cancer Center (MSK) cohort was used for comparison with our results. RESULTS: The top five commonly mutated genes in resected rectal tumor tissue samples following nCRT were TP53 (42%), APC (31%), KRAS (27%), PIK3CA (14%) and FBXW7 (11%). Mutations in the WNT pathway, which was mainly represented by APC mutation, were found to be significantly associated with tumor regression grade (TRG) 3. In our cohort, co-mutations in the receptor tyrosine kinase (RTK)/RAS and WNT pathways were found to be independently associated with reduced risk of recurrent and significantly associated with longer disease-free survival (DFS). In both our cohort and the MSK cohort, co-mutations in the TGF-ß and TP53 pathways were significantly associated with worse DFS. CONCLUSIONS: Resected rectal tumor samples from patients without complete pathological response can be appropriately used to detect mutations. Co-mutations in the TGF-ß and TP53 pathways may provide more prognostic information beyond commonly used clinical factors.

Correction: Critical role of hydrogen bonding between microcrystalline cellulose and g-C3N4 enables highly efficient photocatalysis.

Correction for 'Critical role of hydrogen bonding between microcrystalline cellulose and g-C3N4 enables highly efficient photocatalysis' by Zhaoqiang Wang et al., Chem. Commun., 2024, 60, 204-207, https://doi.org/10.1039/D3CC04800D.

Activate the endogenous Cu2+ switch for Zn(DDC)2 liposomes conversion: Providing a safer and less toxic alternative in cancer therapy.

The ancient anti-alcohol drug disulfiram (DSF) has gained widespread attention for its highly effective anti-tumor effects in cancer treatment. Our previous studies have developed liposome of Cu (DDC)2 to overcome the limitations, like the poor water solubility. However, Cu (DDC)2 liposomes still have shown difficulties in severe hemolytic reactions at high doses and systemic toxicity, which have limited their clinical use. Therefore, this study aims to exploratively investigate the feasibility of using DSF or DDC in combination also can chelate Zn2+ to form zinc diethyldithiocarbamate (Zn (DDC)2). Furthermore, this study prepared stable and homogeneous Zn (DDC)2 liposomes, which were able to be released in the tumor microenvironment (TME). The released Zn (DDC)2 was converted to Cu (DDC)2 with the help of endogenous Cu2+-switch enriched in the TME, which has a higher stability constant compared with Zn (DDC)2. In other words, the Cu2+-switch is activated at the tumor site, completing the conversion of the less cytotoxic Zn (DDC)2 to the more cytotoxic Cu (DDC)2 for effective tumor therapy so that the Zn (DDC)2 liposomes in vivo achieved the comparable therapeutic efficacy and provided a safer alternative to Cu (DDC)2 liposomes in cancer therapy.

Recent Advances in LDH/g-C3N4 Heterojunction Photocatalysts for Organic Pollutant Removal.

Environmental pollution has been decreased by using photocatalytic technology in conjunction with solar energy. An efficient method to obtain highly efficient photocatalysts is to build heterojunction photocatalysts by combining graphitic carbon nitride (g-C3N4) with layered double hydroxides (LDHs). In this review, recent developments in LDH/g-C3N4 heterojunctions and their applications for organic pollutant removal are systematically exhibited. The advantages of LDH/g-C3N4 heterojunction are first summarized to provide some overall understanding of them. Then, a variety of approaches to successfully assembling LDH and g-C3N4 are simply illustrated. Last but not least, certain unmet research needs for the LDH/g-C3N4 heterojunction are suggested. This review can provide some new insights for the development of high-performance LDH/g-C3N4 heterojunction photocatalysts. It is indisputable that the LDH/g-C3N4 heterojunctions can serve as high-performance photocatalysts to make new progress in organic pollutant removal.

Critical role of hydrogen bonding between microcrystalline cellulose and g-C3N4 enables highly efficient photocatalysis.

Developing a highly efficient photocatalyst for energy and environmental applications is urgently required. Herein, graphitic carbon nitride (CN) coupled with microcrystalline cellulose (MCC) (denoted as MCC-X/CN) shows excellent photocatalytic performance for tetracycline (TC) degradation and H2 evolution. And the optimized MCC-0.05/CN shows an improved TC degradation rate (Kapp = 0.019 min-1) and H2 evolution rate (642.71 µmol g-1 h-1), which are 1.9 and 22 times higher than those of pure CN, respectively. This improvement primarily results from hydrogen bonding (H-bonding) between CN and MCC, which enables excellent charge separation and migration, leading to the outstanding photoelectrochemical properties of MCC-0.05/CN.

Analysis of variation characteristics, transport paths, and influencing factors of atmospheric NO2 pollution in Western Europe.

Climate change and air pollution are one of the global environmental problems. It is significant to grasp the air pollution situation of Western Europe in recent 10 years for its or the global pollution control. Based on the OMI tropospheric nitrogen dioxide (NO2) column density data, the spatial and temporal distribution characteristics, variation trend, transmission path, and influencing factors of NO2 in 15 countries in Western Europe from 2011 to 2022 are discussed in this paper. Meanwhile, the annual average spatial and temporal distribution in 2023 is predicted by the random forest (RF) model. The results showed that (1) the 12-year spatial distribution map showed an increasing trend from southwest to northeast, with the border area of the Netherlands and Germany and Milan as two high-value areas, and the overall trend over time was that the high-concentration area gradually shrank, the low-concentration area gradually expanded, and the annual average concentration gradually decreased. (2) The inter-month trend presents a "U" shape, with the mean NO2 pollution ranking in winter > autumn > spring > summer. (3) Natural factors are one of the reasons affecting NO2; for instance, NO2 pollution has a strong positive correlation with the lifted index, relative humidity, and wind speed and a moderately strong negative correlation with precipitable water and air temperature. (4) Exogenous atmospheric transport is another important factor affecting the change of NO2 pollution in Western Europe. The HYSPLIT model is used to analyze the backward trajectory of Milan, Italy, and Nijmegen, Netherlands, in the four seasons of 2022. Both are mainly influenced by westerly airflows, and therefore, the transport effect in the atmosphere brings air pollutants from westerly regions in the atmosphere.

Ginsenoside Rg1 Epigenetically Modulates Smad7 Expression in Liver Fibrosis via MicroRNA-152.

Background: Ginsenoside Rg1, a bioactive component of Ginseng, has demonstrated anti-inflammatory, anti-cancer, and hepatoprotective effects. It is known that the epithelial-mesenchymal transition (EMT) plays a key role in the activation of hepatic stellate cells (HSCs). Recently, Rg1 has been shown to reverse liver fibrosis by suppressing EMT, although the mechanism of Rg1-mediated anti-fibrosis effects is still largely unclear. Interestingly, Smad7, a negative regulator of the transforming growth factor ß (TGF-ß) pathway, is often methylated during liver fibrosis. Whether Smad7 methylation plays a vital role in the effects of Rg1 on liver fibrosis remains unclear. Methods: Anti-fibrosis effects were examined after Rg1 processing in vivo and in vitro. Smad7 expression, Smad7 methylation, and microRNA-152 (miR-152) levels were also analyzed. Results: Rg1 significantly reduced the liver fibrosis caused by carbon tetrachloride, and reduced collagen deposition was also observed. Rg1 also contributed to the suppression of collagenation and HSC reproduction in vitro. Rg1 caused EMT inactivation, reducing Desmin and increasing E-cadherin levels. Notably, the effect of Rg1 on HSC activation was mediated by the TGF-ß pathway. Rg1 induced Smad7 expression and demethylation. The over-expression of DNA methyltransferase 1 (DNMT1) blocked the Rg1-mediated inhibition of Smad7 methylation, and miR-152 targeted DNMT1. Further experiments suggested that Rg1 repressed Smad7 methylation via miR-152-mediated DNMT1 inhibition. MiR-152 inhibition reversed the Rg1-induced promotion of Smad7 expression and demethylation. In addition, miR-152 silencing led to the inhibition of the Rg1-induced EMT inactivation. Conclusion: Rg1 inhibits HSC activation by epigenetically modulating Smad7 expression and at least by partly inhibiting EMT.

20(S)- Protopanaxadiol suppresses hepatic stellate cell activation via WIF1 demethylation-mediated inactivation of the Wnt/ß-catenin pathway.

Background: 20(S)-protopanaxadiol (PPD), one of the main components of ginseng, has anti-inflammatory, anti-estrogenic, and anti-tumor activities. It is known that activated hepatic stellate cells (HSCs) are the primary producers of extracellular matrix (ECM) in the liver, and the Wnt/ß-catenin pathway participates in the activation of HSCs. We aimed to explore whether PPD inhibits liver fibrosis is associated with the Wnt/ß-catenin pathway inactivation. Methods: The anti-fibrotic roles of PPD were examined both in vitro and in vivo. We also examined the levels of Wnt inhibitory factor 1 (WIF1), DNA methyltransferase 1 (DNMT1) and WIF1 methylation. Results: PPD obviously ameliorated liver fibrosis in carbon tetrachloride (CCl4)-treated mice and reduced collagen deposition. PPD also suppressed the activation and proliferation of primary HSCs. Notably, PPD inhibited the Wnt/ß-catenin pathway, reduced TCF activity, and increased P-ß-catenin and GSK-3ß levels. Interestingly, WIF1 was found to mediate the inactivation of the Wnt/ß-catenin pathway in PPD-treated HSCs. WIF1 silencing suppressed the inhibitory effects of PPD on HSC activation and also restored α-SMA and type I collagen levels. The downregulation of WIF1 expression was associated with the methylation of its promoter. PPD induced WIF1 demethylation and restored WIF1 expression. Further experiments confirmed that DNMT1 overexpression blocked the effects of PPD on WIF1 expression and demethylation and enhanced HSC activation. Conclusion: PPD up-regulates WIF1 levels and impairs Wnt/ß-catenin pathway activation via the down-regulation of DNMT1-mediated WIF1 methylation, leading to HSC inactivation. Therefore, PPD may be a promising therapeutic drug for patients with liver fibrosis.

Regional transarterial chemoembolization combined with chemoradiotherapy for locally advanced rectal cancer: a retrospective study of a new combination.

Objectives: Locally advanced rectal cancer (LARC) has a high risk of distant metastasis (DM). Currently, many treatment courses of LARC have arisen, but patients' DM status has not significantly improved. This study was designed to compare the effect between preoperative regional transarterial chemoembolization combined with neoadjuvant chemoradiotherapy and standard neoadjuvant therapy on preventing DM in patients with LARC. Methods: A total of 81 LARC patients between July 2013 and May 2018 were enrolled in this retrospective study. Among them, 44 patients received preoperative regional transarterial chemoembolization combined with concurrent chemoradiotherapy (the interventional group), and 37 patients received only neoadjuvant chemoradiotherapy (the control group). The baseline data; preoperative toxicities; postoperative DM rate within 1, 2, and 3 years; and postoperative complications were compared between the two groups. Results: All patients successfully completed their treatments. There were no significant differences between the two groups in age, gender, tumor size, distance between the tumor and anal verge, CEA level, lymphovascular invasion, or tumor stage before treatment. The pathological T staging post-treatment in the interventional group was significantly reduced compared to that of the control group (p = 0.025). There were no significant differences between groups in DM rates within 1 and 2 years after surgery. In terms of DM rate within 3 years after surgery, the interventional group was significantly lower than that of the control group (9.1% vs. 29.7%, p = 0.036). Conclusion: Preoperative regional transarterial chemoembolization combined with concurrent chemoradiotherapy may play an important role in reducing postoperative DM in LARC.