Association Between Vitamin B12 Intake and Mortality in Patients with Colorectal Cancer: The US National Health and Nutrition Examination Survey, 1999-2018.

Vitamin B12 plays a role in DNA methylation, influencing the 1-carbon cycle; However, its effect on colorectal cancer (CRC) mortality remains uncertain. This study assessed the relationship between vitamin B12 intake and all-cause and cancer-specific mortality among CRC patients. We analyzed data from the NHANES from 1999 to 2018, using multivariable Cox regression, competing risk model, Kaplan-Meier survival curves, and stratified analysis with interaction effects. The studied involved 4,554 cancer patients (mean age 65.8 years, 47.6% males). Results from multivariate Cox regression indicated that each additional 1 mcg/day of dietary vitamin B12 independently increased the risk of all-cause (HR, 1.07; 95% CI: 1.04-1.09, p < 0.001) and cancer-specific mortality (HR, 1.04; 95% CI, 1.02-1.06; p < 0.001). Kaplan-Meier curves indicated a higher risk of all-cause mortality with increased vitamin B12 intake (Log rank p = 0.01). Subgroup analysis suggested that higher vitamin B12 intake correlated with increased all-cause mortality risk, especially in individuals with higher protein (HR, 1.04; 95% CI, 1.02-1.06; p = 0.019) or carbohydrate intake (HR, 1.03; 95% CI, 1.01-1.05; p = 0.04). Thus, higher vitamin B12 intake correlates with increased all-cause and cancer-specific mortality in CRC patients, particularly those with higher protein or carbohydrate intake.

Clinicopathologic and endoscopic features of sessile serrated lesions and conventional adenomas: a large inpatient population-based study in China.

Objectives: Sessile serrated lesions (SSLs) are precursors of sporadic colorectal cancer (CRC) and have distinct characteristics compared with conventional adenomas (CAs). Several lifestyle and environmental factors may play critical roles in the development of advanced lesions. Our aim is to describe the features of SSLs and CAs and further explore risk factors for advanced lesions. Methods: This is an observational study that collected demographic, endoscopic, and histological data from the China-Japan Friendship Hospital among the inpatient population with pathologically reported as SSL or CA between 2015 and 2022. We analyzed the clinicopathology and endoscopic differences between SSL alone, CA alone, and synchronous SSL+CA groups, and identified risk factors using multiple regression analysis. Results: A total of 9236 polyps from 6598 patients were included in the cohort. Patients with SSL+CA were more likely to be older (p=0.008), while individuals with SSL alone had a higher proportion of early-onset polyps (p<0.001), and SSLs were more common in advanced polyps than CAs (p<0.001). A greater proportion of advanced polyps in the SSL and CA groups were diagnosed as Yamada III, Yamada IV, and laterally spreading tumor (p=0.002, p<0.001, respectively), and multiple SSLs and CAs were more represented in nonadvanced polyps than in advanced polyps. In multiple regression analysis, older patients were more likely to develop advanced SSLs (aOR 1.05, 95% CI 1.02-1.09, p=0.005). Conclusion: SSLs and CAs have diverse demographic, endoscopic, and histological characteristics, and their advanced lesions share different risk factors, which advances the understanding of the etiology and progression of SSLs.

Electrochemical reductive removal of trichloroacetic acids by a three-dimensional binderless carbon nanotubes/ CoP/Co foam electrode: Performance and mechanism.

Numerous chlorinated disinfection by-products (DBPs) are produced during the chlorination disinfection of water. Among them, chloroacetic acids (CAAs) are of great concern due to their potential human carcinogenicity. In this study, effective electrocatalytic dechlorination of trichloroacetic acids (TCAA), a typical CAAs, was achieved in the electrochemical system with the three-dimensional (3D) self-supported CoP on cobalt foam modified by carbon nanotubes (CNT/CoP/CF) as the cathode. At a 10 mA cm-2 current density, 74.5% of TCAA (500 µg L-1) was converted into AA within 100 min. In-situ growth of CoP increased the effective electrochemical surface area of the electrode. Electrodeposited CNT promoted electron transfer from the electrode surface to TCAA. Therefore, the production of surface-adsorbed atomic hydrogen (H*) on CNT/CoP/CF was improved, further resulting in excellent electrochemical dechlorination of TCAA. The dechlorination pathway of TCAA proceeded into acetic acids via direct electronic transfer and H*-mediated reduction on CNT/CoP/CF electrode. Additionally, the electroreduction efficiency of CNT/CoP/CF for TCAA exceeded 81.22% even after 20 cycles. The highly efficient TCAA reduction performance (96.57%) in actual water revealed the potential applicability of CNT/CoP/CF in the complex water matrix. This study demonstrated that the CNT/CoP/CF is a promising non-noble metal cathode to remove chlorinated DBPs in practice.

AAV-Mediated Gene Therapy Restores Hearing in Patients with DFNB9 Deafness.

Mutations in OTOFERLIN (OTOF) lead to the autosomal recessive deafness 9 (DFNB9). The efficacy of adeno-associated virus (AAV)-mediated OTOF gene replacement therapy is extensively validated in Otof-deficient mice. However, the clinical safety and efficacy of AAV-OTOF is not reported. Here, AAV-OTOF is generated using good manufacturing practice and validated its efficacy and safety in mouse and non-human primates in order to determine the optimal injection dose, volume, and administration route for clinical trials. Subsequently, AAV-OTOF is delivered into one cochlea of a 5-year-old deaf patient and into the bilateral cochleae of an 8-year-old deaf patient with OTOF mutations. Obvious hearing improvement is detected by the auditory brainstem response (ABR) and the pure-tone audiometry (PTA) in these two patients. Hearing in the injected ear of the 5-year-old patient can be restored to the normal range at 1 month after AAV-OTOF injection, while the 8-year-old patient can hear the conversational sounds. Most importantly, the 5-year-old patient can hear and recognize speech only through the AAV-OTOF-injected ear. This study is the first to demonstrate the safety and efficacy of AAV-OTOF in patients, expands and optimizes current OTOF-related gene therapy and provides valuable information for further application of gene therapies for deafness.

Effects of Adjuvant Chemotherapy on Early-onset Stage II Colon Cancer at Different Tumor Sites.

OBJECTIVES: Left-sided colon cancer (LSCC) and right-sided colon cancer (RSCC) have shown distinct clinical and prognostic features. We investigated the effect of adjuvant chemotherapy (ACT) on cause-specific survival (CSS) in patients with stage II LSCC and RSCC. METHODS: Using the Surveillance, Epidemiology and End Results (SEER) database, a cohort of patients with stage II colon cancer, aged between 20 and 49 years was identified. Both Cox proportional hazards regression and Kaplan-Meier survival analysis as well as propensity score matching were used. RESULTS: Overall, 5633 patients were eligible. Patients with RSCC were more likely to be male, black, and younger, with a poor grade and histologic type, and were more likely to have more regional nodes examined and larger tumor size. After propensity score matching, CSS was significantly superior in patients with RSCC compared to those with LSCC (Hazard Ratio (HR): 0.80, 95% CI: 0.68-0.95, P =0.01). However, no survival benefit was observed for patients with LSCC after ACT (HR: 1.10, 95% CI: 0.90-1.35, P =0.35), and surprisingly, ACT was found to do more harm than good in patients with RSCC (HR: 1.31, 95% CI: 1.05-1.63, P =0.02). Even among patients with high-risk features such as T4 stage and regional nodes examined<12 in both groups, ACT still did not improve CSS except for T4 stage LSCC (HR: 0.65, 95% CI: 0.44-0.97, P =0.02). CONCLUSIONS: The results of this analysis indicate that the prognosis of RSCC is better than that of LSCC in stage II colon cancer, and ACT did not improve CSS in patients with either LSCC or RSCC. Even in patients with parts of high-risk features, ACT still did not improve CSS, except for T4 stage LSCC.

Leukocyte immunoglobulin-like receptor B2 overexpression as a promising therapeutic target and noninvasive screening biomarker for colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) has become the second most deadly malignancy in the world, and the exploration of screening markers and precise therapeutic targets is urgent. Our previous research identified leukocyte immunoglobulin-like receptor B2 (LILRB2) protein as a characteristic protein of CRC, but the association between LILRB2 expression and clinicopathological features, the internal mechanism related to CRC progression, and screening diagnostic efficacy are not clear. Therefore, we hypothesized that LILRB2 is significantly highly expressed in CRC tissues, correlated with advanced stage and a poor prognosis, and could be used as a therapeutic target and potential screening biomarker for CRC. AIM: To explore whether LILRB2 can be used as a potential therapeutic target and noninvasive screening biomarker for CRC. METHODS: Patients who underwent radical surgery for CRC at China-Japan Friendship Hospital between February 2021 and October 2022 were included. Cancer and paracancerous tissues were collected to verify LILRB2 expression, and the association between LILRB2 expression and clinicopathological features was analysed. Serum was collected from CRC patients, adenoma patients and healthy controls during the same period to assess the diagnostic value of LILRB2 as a noninvasive screening biomarker, and its diagnostic value was further compared with that of the traditional markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). RESULTS: A total of 58 CRC patients were included, and LILRB2 protein was significantly overexpressed in cancer tissues compared with paracancerous tissues (P < 0.001). Angiopoietin-like protein 2 (ANGPTL2) protein, as the ligand of LILRB2, was synergistically overexpressed in CRC tissues (P < 0.001), and overexpression of LILRB2 and ANGPTL2 protein was significantly correlated with poor to moderate differentiation, vascular involvement, lymph node metastasis, distant metastasis, advanced tumor-node-metastasis stage and a poor prognosis (P < 0.05), which suggested that LILRB2 and ANGPTL2 are closely associated with CRC progression. In addition, serum LILRB2 concentrations increased stepwise in healthy individuals, adenoma patients and CRC patients with statistically significant differences. The sensitivity of serum LILRB2 for the diagnosis of CRC was 89.74%, the specificity was 88.89%, the area under the curve was 0.95, and the diagnostic efficacy was better than that of conventional CEA and CA19-9. CONCLUSION: LILRB2 protein can be used as a potential novel therapeutic target and noninvasive screening biomarker for CRC, which is beneficial for early screening and precise treatment.

Regulation of M1/M2 Polarization in LPS-Stimulated Macrophages by 1,25(OH)2D3.

Objective: This study aims to investigate the impact of 1,25(OH)2D3 on the polarization of LPS-stimulated macrophages and the underlying regulatory mechanisms. Methods: Primary macrophages were isolated and identified using immunofluorescence assays to detect macrophage biomarker expression levels. RT-PCR was employed to measure the expression of Arginase 1 (Arg-1), Interleukin-10 (IL-10), Inducible isoform of nitric oxide synthase (iNOS), and Tumor necrosis factor-α (TNF-α) in macrophages treated with various strategies. Western blotting assessed the protein expression levels of AKT1, p-AKT1, NF-κB p65, p-NF-κB p65, STAT3, and p-STAT3 in LPS-stimulated macrophages exposed to different concentrations of 1,25(OH)2D3. Results: As the LPS concentration increased from 0 to 0.5 mg/L, Arg-1, IL-10, iNOS, and TNF-α expression levels significantly increased. However, at LPS concentrations ranging from 1 mg/L to 10 mg/L, the expression of Arg-1, IL-10, iNOS, and TNF-α displayed a trend from increase to decline. The highest M2 polarization (Arg-1 and IL-10) was observed in macrophages stimulated with 0.5 mg/L LPS among the lower concentrations, while the highest M1 polarization (iNOS and TNF-α) was observed in macrophages stimulated with 5 mg/L LPS among the higher concentrations. Subsequent experiments utilized 0.5 mg/L and 5 mg/L LPS as incubation concentrations. Under LPS stimulation, iNOS was significantly upregulated, surpassing the expression level of IL-10, a marker of M2 macrophages. The introduction of 1,25(OH)2D3 facilitated M2 polarization, with 50 nM as the incubation concentration of 1,25(OH)2D3. Furthermore, 1,25(OH)2D3 reversed the elevated expression of p-AKT1, p-NF-κB p65, and p-STAT3 in macrophages stimulated with 5 mg/L LPS. Conclusions: 1,25(OH)2D3 effectively regulates the M1/M2 polarization in LPS-stimulated macrophages.

B-seco Limonoids with anti-inflammatory activity from Tetradium fraxinifolium (Hook.) T.G.Hartley.

Fraxinifolines A-F (1-6), six new B-seco limonoids, together with four known A,D-di-seco ones, were isolated from the twigs with leaves of Tetradium fraxinifolium. Their structures with absolute configurations were elucidated on the basis of analysis of MS, NMR, single-crystal X-ray diffraction and biogenetic pathway. An anti-inflammatory bioassay in vitro showed limonoids 1-3 had significant immunosuppressive effect against the production of pro-inflammatory cytokines (IL-1ß and/or TNF-α) in lipopolysaccharide (LPS)-stimulated RAW264.7 cells.

Radiographic and α-fetoprotein response predict pathologic complete response to immunotherapy plus a TKI in hepatocellular carcinoma: a multicenter study.

BACKGROUND: Pathologic complete response (pCR) following preoperative systemic therapy is associated with improved outcomes after subsequent liver transplant/resection in hepatocellular carcinoma (HCC). However, the relationship between radiographic and histopathological response remains unclear. METHODS: We retrospectively examined patients with initially unresectable HCC who received tyrosine kinase inhibitor (TKI) plus anti-programmed death 1 (PD-1) therapy before undergoing liver resection between March 2019 and September 2021 across 7 hospitals in China. Radiographic response was evaluated using mRECIST. A pCR was defined as no viable tumor cells in resected samples. RESULTS: We included 35 eligible patients, of whom 15 (42.9%) achieved pCR after systemic therapy. After a median follow-up of 13.2 months, tumors recurred in 8 non-pCR and 1 pCR patient. Before resection, there were 6 complete responses, 24 partial responses, 4 stable disease cases, and 1 progressive disease case, per mRECIST. Predicting pCR by radiographic response yielded an area under the receiver operating characteristic curve (AUC) of 0.727 (95% CI: 0.558-0.902), with an optimal cutoff value of 80% reduction in the enhanced area in MRI (called major radiographic response), which had a 66.7% sensitivity, 85.0% specificity, and a 77.1% diagnostic accuracy. When radiographic response was combined with α-fetoprotein response, the AUC was 0.926 (95% CI: 0.785-0.999); the optimal cutoff value was 0.446, which had a 91.7% sensitivity, 84.6%, specificity, and an 88.0% diagnostic accuracy. CONCLUSIONS: In patients with unresectable HCC receiving combined TKI/anti-PD 1 therapy, major radiographic response alone or combined with α-fetoprotein response may predict pCR.

Qingre Xingyu recipe exerts inhibiting effects on ulcerative colitis development by inhibiting TNFα/NLRP3/Caspase-1/IL-1ß pathway and macrophage M1 polarization.

As a chronic inflammatory bowel disease, ulcerative colitis (UC) imposes a significant burden on public healthcare worldwide due to its increasing morbidity. Chinese medicines are regarded as potent therapeutic agents for UC treatment with minimal side effects. In the present study, we sought to determine the novel role of a traditional medicine Qingre Xingyu (QRXY) recipe in the development of UC and aimed to contribute to the currently available knowledge about UC by exploring the downstream mechanism of QRXY recipe in UC. Mouse models of UC were established by injections with dextran sulphate sodium (DSS), where the expression of tumor necrosis factor-alpha (TNFα), NLR family pyrin domain containing 3 (NLRP3), and interleukin-1ß (IL-1ß) was determined followed by an analysis of their interactions. The DSS-treated NLRP3 knockout (-/-) Caco-2 cell model was successfully constructed. The in vitro and in vivo effects of the QRXY recipe on UC were investigated with the determination of disease activity index (DAI), histopathological scores, transepithelial electrical resistance, FITC-dextran, as well as cell proliferation and apoptosis. In vivo and in vitro experiments indicated that the QRXY recipe reduced the degree of intestinal mucosal injury of UC mice and functional damage of DSS-induced Caco-2 cells by inhibition of the TNFα/NLRP3/caspase-1/IL-1ß pathway and M1 polarization of macrophages, and TNFα overexpression or NLRP3 knockdown could counterweigh the therapeutic effects of QRXY recipe. To conclude, our study elicited that QRXY inhibited the expression of TNFα and inactivated the NLRP3/Caspase-1/IL-1ß pathway, thereby alleviating intestinal mucosal injury and relieving UC in mice.

Age-stratified proteomic characteristics and identification of promising precise clinical treatment targets of colorectal cancer.

Colorectal cancer (CRC) is an extremely lethal disease worldwide. However, the underlying pathogenesis remains unclear. This study aimed to reveal the distinct characteristics of age-stratified CRC at the protein level and explore precise treatment targets. Patients who underwent surgical removal with pathologically confirmed CRC at China-Japan Friendship Hospital from January 2020 to October 2021 were recruited, cancer and para-carcinoma tissues (> 5 cm) were detected by mass spectrometry. Ninety-six clinical samples were collected and divided into three groups according to age: young (≤ 50 years), middle-aged (51-69 years), and old (≥ 70 years). Quantitative proteomic analysis was performed, as well as comprehensive bioinformatic analysis based on the Human Protein Atlas, Clinical Proteomic Tumor Analysis Consortium and Connectivity Map databases. The numbers of upregulated and downregulated proteins were 1315 and 560 in the young group, 757 and 311 in the old group, and 1052 and 468 in the middle-aged group, respectively. Bioinformatic analysis showed that these differentially expressed proteins had different molecular functions and participated in extensive signaling pathways. We also revealed ADH1B, ARRDC1, GATM, GTF2H4, MGME1, and LILRB2 as possible cancer-promoting molecules, which might serve as potential prognostic biomarkers and precise therapeutic targets for CRC. SIGNIFICANCE: This study comprehensively characterized the proteomic profiles of age-stratified colorectal cancer patients, focusing on the differentially expressed proteins between cancer and paracancerous tissues in different age groups, in an effort to find corresponding potential prognostic biomarkers and therapeutic targets. In addition, this study provides potentially valuable clinical small molecule inhibitory agents.

Exposed Zinc Sites on Hybrid ZnIn2 S4 @CdS Nanocages for Efficient Regioselective Photocatalytic Epoxide Alcoholysis.

Photocatalytic epoxide alcoholysis through C-O bond cleavage and formation has emerged as an alternative to synthesizing anti-tumoral pharmaceuticals and fine chemicals. However, the lack of crucial evidence to interpret the interaction between reactants and photocatalyst surface makes it challenging for photocatalytic epoxide alcoholysis with both high activity and regioselectivity. In this work, we report the hierarchical ZnIn2 S4 @CdS photocatalyst for epoxide alcoholysis with high regioselectivity nearly 100 %. Mechanistic studies unveil that the precise activation switch on exposed Zn acid sites for C-O bond polarization and cleavage has a critical significance for achieving efficient photocatalytic performance. Furthermore, the establishment of Z-scheme heterojunction facilitates the interface charge separation and transfer. Remarkably, the underlying regioselective photocatalytic reaction pathway has been distinctly revealed.

Interlayer Structure and Chemistry Engineering of MXene-Based Anode for Effective Capture of Chloride Anions in Asymmetric Capacitive Deionization.

Negatively charged surfaces and readily oxidizabile characteristics fundamentally restrict the use of MXene building blocks as anodes for anion intercalation. Herein, by embedding bacterial cellulose nanofibers with conformal polypyrrole coating (BC@PPy) and populating them between MXene (Ti3C2Tx) interlayers, we enable the fabricated MXene/BC@PPy (MBP) composite films to be highly efficient anodes for Cl--capturing in asymmetric capacitive deionization (CDI) systems. Performance gains are realized due to the surface electronegativity of MXene nanosheets becoming compensated by positively charged BC@PPy nanofibers, alleviating electrostatic repulsion, thus realizing reversible Cl- intercalation. More crucially, the anodization voltage of MBP is effectively enhanced as a result of the increase of the Ti valence state in MXene nanosheets with the addition of the BC@PPy spacer. Furthermore, BC@PPy nanopillars effectively enlarge the interlayer space for facile Cl- de-/intercalation, improve the vertical electron transfer between loosely deposited MXene nanosheets, and perform as additional active materials for Cl--capturing. Consequently, the MBP anode exhibits a promising desalination capacity of up to 17.56 mg g-1 at 1.2 V with a high capacity retention of 94.6% after 30 cycles in an asymmetric CDI system. This work offers a simple and effective strategy to unlock the application potential of MXene building blocks as anodes for Cl--capturing in electrochemical desalination.

Effectiveness and safety of lenvatinib plus anti-programmed death-1 antibodies in patients with hepatocellular carcinoma: A real-world cohort study.

OBJECTIVE: Lenvatinib plus anti-programmed death-1 (anti-PD-1) antibody combinations have shown potent anti-tumor effect in phase I/II trials in advanced or unresectable hepatocellular carcinoma (HCC), but real-world data are limited. METHODS: To investigate the effectiveness and safety of lenvatinib plus anti-PD-1 antibodies in a real-world cohort, we retrospectively evaluated 210 patients with unresectable or advanced HCC treated with these regimens between October 2018 and February 2022. RESULTS: The objective response rate and disease control rate per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 were 28.1% and 75.2%. Median overall survival (OS) and progression-free survival (PFS) in the overall cohort were 17.2 and 8.4 months, respectively. Median OS and PFS of patients receiving first-line treatment reached 18.9 and 9.6 months. Median OS was significantly longer in patients with Child-Pugh class A versus B (18.8 vs. 5.9 months, respectively), as was median PFS (9.1 vs. 4.4 months). Patients with albumin-bilirubin (ALBI) grade 1 versus grade 2/3 also had significantly greater median OS (23.5 vs. 13.4 months). Treatment-related adverse events (AEs) occurred in 79.5% of patients. Patients with ALBI grade 2/3 had a higher rate of grade 3/4 AEs than patients with ALBI grade 1 (57.5% vs. 38.5%). CONCLUSION: Lenvatinib combined with anti-PD-1 antibody therapy was effective in patients with sufficient liver function reserve. Further study is needed to improve therapeutic efficacy and AE management in patients with Child-Pugh class B or ALBI grade 2/3.

Prediction of inlet SO2 concentration of wet flue gas desulfurization (WFGD) by operation parameters of coal-fired boiler.

Circulating fluidized bed (CFB) boilers with wet flue gas desulfurization (WFGD) system is a popular technology for SO2 removal in the coal-fired thermal power plant. However, the long response time of continues emission monitoring system (CEMS) and the hardness of continuously monitoring the coal properties leads to the difficulties for controlling WFGD. It is important to build a model that is adaptable to the fluctuation of load and coal properties, which can obtain the SO2 concentration ahead CEMS, without relying on coal properties. In this paper, a prediction model of inlet SO2 concentration of WFGD considering the delay between the features and target based on long-short term memory (LSTM) network with auto regression feature is established. The SO2 concentration can be obtained 90 s earlier than CEMS. The model shows good adaptability to the fluctuation of SO2 concentration and coal properties. The root-mean-squared error (RMSE) and R squared (R2) of the model are 30.11 mg/m3 and 0.986, respectively. Meanwhile, a real-time prediction system is built on the 220 t/h unit. A field test for long-term operation has been conducted. The prediction system is able to continuously and accurately predict the inlet SO2 concentration of the WFGD, which can provide the operators with an accurate reference for the control of WFGD.

An integrated approach for quantifying source apportionment and source-oriented health risk of heavy metals in soils near an old industrial area.

Soil contamination of heavy metals (HMs) caused by the long-term industrial activities has become a major environmental issue due to its adverse effects on human health and ecosystem. In this paper, 50 soil samples were analyzed to evaluate the contamination characteristics, source apportionment and source-oriented health risk of HMs in soils near an old industrial area in NE China by applying an integrated approach of Pearson correlation analysis, Positive matrix factorization (PMF) model and Monte Carlo simulation. The results showed that the mean concentrations of all HMs greatly exceeded the soil background values (SBV), and the surface soils in the study area were heavily polluted with HMs, displaying a very high ecological risk. The toxic HMs emitted from the bullet production were identified as the primary source of HMs contamination in soils, with a contribution rate of 33.3%. The human health risk assessment (HHRA) suggested that the Hazard quotient (HQ) values of all HMs for children and adults are within the acceptable risk level (HQ < 1). The carcinogenic risk (CR) values of HMs for children and adults significantly exceeded the acceptable threshold of 1E-6 with a basic trend: As > Pb > Cr > Co > Ni, indicating a high cancer risk. For source-oriented health risk, the CR of four pollution sources for children and adults shows a same trend: Factor 4 > Factor 3 > Factor 2 > Factor 1. Among those, the source of HMs pollution from bullet production is the largest contributor to cancer risk, and As and Pb are the most important HMs pollutants that cause cancer risk to humans. The present study sheds some light on the contamination characteristics, source apportionment and source-health risk assessment of HMs in industrially contaminated soils, which helps improve the management of environmental risk control, prevention and remediation.

Discovery of Small-Molecule Autophagy Inhibitors by Disrupting the Protein-Protein Interactions Involving Autophagy-Related 5.

One possible strategy for modulating autophagy is to disrupt the critical protein-protein interactions (PPIs) formed during this process. Our attention is on the autophagy-related 12 (ATG12)-autophagy-related 5 (ATG5)-autophagy-related 16-like 1 (ATG16L1) heterotrimer complex, which is responsible for ATG8 translocation from ATG3 to phosphatidylethanolamine. In this work, we discovered a compound with an (E)-3-(2-furanylmethylene)-2-pyrrolidinone core moiety (T1742) that blocked the ATG5-ATG16L1 and ATG5-TECAIR interactions in the in vitro binding assay (IC50 = 1-2 µM) and also exhibited autophagy inhibition in cellular assays. The possible binding mode of T1742 to ATG5 was predicted through molecular modeling, and a batch of derivatives sharing essentially the same core moiety were synthesized and tested. The outcomes of the in vitro binding assay and the flow cytometry assay of those newly synthesized compounds were generally consistent. This work has validated our central hypothesis that small-molecule inhibitors of the PPIs involving ATG5 can tune down autophagy effectively, and their pharmaceutical potential may be further explored.

Promising Clinical Applications of Hydrogels Associated With Precise Cancer Treatment: A Review.

Gastrointestinal cancer is one of the most malignant tumors with high morbidity and mortality, especially colorectal cancer, which has become the second leading cause of cancer-related deaths worldwide. Targeted drug treatment and precise endoscopic resection can significantly improve the overall survival rate and greatly extend the life span. Promising biomedical applications of hydrogels would represent hopeful therapeutic alternatives for patients with different kinds of diseases, particularly providing precise therapy for cancer patients. Although the intersection field of material science and biomedical science has made tremendous advances, major challenges remain. In this review, the application of hydrogel-based technology in cancer precision medicine is the focus of attention, which is the development trend of multidisciplinary cooperation in the future. First, we provide the current clinical landscape of hydrogel applications, and then we highlight precision oncology, including personalized drug treatment and accurate endoscopic intervention. Finally, we discuss major challenges for their clinical translation that have not yet been overcome and future perspectives on cancer precision medicine.