Comprehensive characterization of ß-alanine metabolism-related genes in HCC identified a novel prognostic signature related to clinical outcomes.

Hepatocellular carcinoma (HCC) stands out as the most prevalent type of liver cancer and a significant contributor to cancer-related fatalities globally. Metabolic reprogramming, particularly in glucose, lipid, and amino acid metabolism, plays a crucial role in HCC progression. However, the functions of ß-alanine metabolism-related genes (ßAMRGs) in HCC remain understudied. Therefore, a comprehensive evaluation of ßAMRGs is required, specifically in HCC. Initially, we explored the pan-cancer landscape of ßAMRGs, integrating expression profiles, prognostic values, mutations, and methylation levels. Subsequently, scRNA sequencing results indicated that hepatocytes had the highest scores of ß-alanine metabolism. In the process of hepatocyte carcinogenesis, metabolic pathways were further activated. Using ßAMRGs scores and expression profiles, we classified HCC patients into three subtypes and examined their prognosis and immune microenvironments. Cluster 3, characterized by the highest ßAMRGs scores, displayed the best prognosis, reinforcing ß-alanine's significant contribution to HCC pathophysiology. Notably, immune microenvironment, metabolism, and cell death modes significantly varied among the ß-alanine subtypes. We developed and validated a novel prognostic panel based on ßAMRGs and constructed a nomogram incorporating risk degree and clinicopathological characteristics. Among the model genes, EHHADH has been identified as a protective protein in HCC. Its expression was notably downregulated in tumors and exhibited a close correlation with factors such as tumor staging, grading, and prognosis. Immunohistochemical experiments, conducted using HCC tissue microarrays, substantiated the validation of its expression levels. In conclusion, this study uncovers ß-alanine's significant role in HCC for the first time, suggesting new research targets and directions for diagnosis and treatment.

Pan-Cancer Analysis Shows that KIFC2 is a Potential Prognostic and Immunotherapeutic Biomarker for Multiple Cancer Types Including Bladder Cancer.

KIFC2 plays an important role in prostate cancer progression and chemotherapy resistance, but the mechanism of its involvement in other malignancies remains unclear. Therefore, this study aimed to analyze and validate the mechanism of effect of KIFC2 in multiple tumors. Bioinformatic analysis was performed in conjunction with multiple databases (The Cancer Genome Atlas, Genotype-Tissue Expression Project, Human Protein Atlas, etc.) to fully explore the potential role of KIFC2 within individual tumors and to analyze the correlation with major research components such as prognosis, mutations, and the tumor microenvironment. The expression of KIFC2 demonstrates a significant correlation with the prognosis, clinical phenotype, tumor mutational burden, microsatellite instability, and tumor microenvironment across various malignancies and is associated with the modulation of diverse functional and signaling pathways. The differences in the expression of KIFC2 in the bladder cancer tissues (14 pairs) were statistically significant. The pan-cancer analysis in this study revealed the multifunctionality of KIFC2 in a variety of tumors, indicating a possible prognostic predictor and potential therapeutic target for tumors.

The Molecular Characteristics and Therapeutic Implications of O-Glycan Synthesis in Pancreatic Cancer by Integrating Transcriptome and Single-Cell Data.

BACKGROUND: Glycans constitute the primary components of proteins that regulate key carcinogenic processes in cancer progression. This study investigated the significance of O-glycan synthesis in the pathogenesis, outcome, and therapy of pancreatic cancer (PC). METHODS: Transcriptomic data and clinical prognostic information of PC were acquired via TCGA and GEO databases. CSA database was used to obtain single-cell data of PC. The O-glycan biosynthesis signaling pathway and its related genes were acquired via the MSigDB platform. The nonnegative matrix factorization (NMF) clustering was utilized to construct the O-glycan biosynthesis-associated molecular subtypes in PC. The LASSO and Cox regression were utilized to build the prognostic prediction model. We utilized real-time quantitative PCR (qRT-PCR) to verify the expressed levels of model genes. Single-cell analysis was utilized to investigate the levels of target genes and O-glycan biosynthesis signaling pathway in the PC tumour microenvironment. RESULTS: We obtained 30 genes related to O-glycan biosynthesis, among which 15 were associated with the prognosis of PC. All PC samples were grouped into two distinct molecular subtypes associated with O-glycan biosynthesis: OGRGcluster C1 and OGRGcluster C2, and compared to OGRGcluster C1. PCs in OGRGcluster C2 had a more advanced clinical stage and pathological grade, worse prognosis, and more active O-glycan biosynthesis function. Immune analysis indicated that naïve B cell, CD8+ T cell, memory-activated CD4+ T cell, and monocytes displayed remarkably higher infiltration levels in OGRGcluster C1 while resting NK cell, macrophages M0, resting dendritic cell, activated dendritic cell, and neutrophils exhibited markedly higher infiltration levels in OGRGcluster C2. OGRGcluster C1 exhibited higher sensitivities to drugs, such as cisplatin, irinotecan, KRAS(G12C) inhibitor-12, oxaliplatin, paclitaxel, and sorafenib. Besides, we built the O-glycan biosynthesis-related prognostic model (including SPRR1B, COL17A1, and ECT2) with a good prediction performance. SPRR1B, COL17A1, and ECT2 were remarkably highly expressed in PC tissues and linked to a poor outcome. Single-cell analysis revealed that Oglycan biosynthesis was observed only in PC, and consistent with this, the target genes were significantly enriched in PC. CONCLUSION: We first constructed molecular subtypes and prognostic models related to O-glycan biosynthesis in PC. It is clear that O-glycan biosynthesis is related to the development, prognosis, immune microenvironment, and treatment of PC. This provides new strategies for stratification, diagnosis, and treatment of PC patients.

Magnolol promotes the autophagy of esophageal carcinoma cells by upregulating HACE1 gene expression.

Esophagus cancer (EC) is one of the most aggressive malignant digestive system tumors and has a high clinical incidence worldwide. Magnolol, a natural compound, has anticancer effects on many cancers, including esophageal carcinoma, but the underlying mechanism has not been fully elucidated. Here, we first find that magnolol inhibits the proliferation of esophageal carcinoma cells and enhances their autophagy activity in a dose- and time-dependent manner. This study demonstrates that magnolol increases the protein levels of LC3 II, accompanied by increased HACE1 protein levels in both esophageal carcinoma cells and xenograft tumors. HACE1-knockout (KO) cell lines are generated, and the ablation of HACE1 eliminates the anti-proliferative and autophagy-inducing effects of magnolol on esophageal carcinoma cells. Additionally, our results show that magnolol primarily promotes HACE1 expression at the transcriptional level. Therefore, this study shows that magnolol primarily exerts its antitumor effect by activating HACE1-OPTN axis-mediated autophagy. It can be considered a promising therapeutic drug for esophageal carcinoma.

The potential of EZH2 expression to facilitate treatment choice in stage II colorectal adenocarcinoma.

BACKGROUND: The current selection criteria of patients with stage II colorectal carcinoma (CRC) suitable for adjuvant therapy are not satisfactory. Enhancer of zeste homolog 2 (EZH2) has been demonstrated to be over-expressed in CRC. However, data regarding the role of EZH2 in CRC survival remains controversial, and little is known about it in stage II CRC. Thus, we conducted this study to investigate the clinical significance of EZH2 expression in stage II CRC. METHODS: Cases with stage II CRC resected between 2015 and 2018 were retrospectively reviewed. EZH2 expression was analyzed by immunohistochemistry using tissue microarrays. The relationship between EZH2 expression and clinicopathological variables was analyzed. Survival curves were estimated by the Kaplan-Meier approach. RESULTS: We found high EZH2 expression in 134 of 221 analyzable stage II tumors (60.63%). No significant associations were observed between EZH2 expression and common clinicopathological factors. Survival analyses showed that cases receiving surgery alone had inferior overall survival (OS) than those receiving surgery and chemotherapy (P=0.0075) in stage II CRC with high EZH2 expression, however, metastasis-free survival (MFS) was similar between these two subgroups. Treatment choice had no impact on the survival of stage II CRC with low EZH2 expression. CONCLUSION: The OS of stage II CRC with high EZH2 expression improved more strikingly with surgery and adjuvant chemotherapy than with surgery alone, which suggests the potential of EZH2 expression as a biomarker to help identify a subgroup of early-stage CRC benefiting from surgery and adjuvant chemotherapy. More large-scale studies are warranted to corroborate this finding and to further evaluate the predictive nature of EZH2.

The potential causal relationship between various lifestyles and depression: a univariable and multivariable Mendelian randomization study.

Background: Previous studies have shown that lifestyle was associated with depression. Thus, the aim of this study was to examine the causality between multiple lifestyles and depression by Mendelian randomization (MR) analysis. Methods: The single-nucleotide polymorphisms (SNPs) of depression, alcoholic drinks per week, sleeplessness or insomnia, body mass index (BMI), mood swings, weekly usage of mobile phone in the last 3 months, beef intake, cooked vegetable intake, and "smoking status: never" were acquired from the Integrative Epidemiology Unit Open genome-wide association study database. Causal effects of eight exposure factors and depression were investigated using MR-Egger, weighted median, inverse variance weighted (IVW), simple mode, and weighted mode, and results were primarily referred to IVW. Subsequently, univariable MR (UVMR) analysis was performed on eight exposure factors and depression, separately. In addition, sensitivity analysis, including heterogeneity test, horizontal pleiotropy, and leave-one-out (LOO) methods, was conducted to evaluate the stability of MR results. Furthermore, multivariable MR (MVMR) analysis was carried out. Results: UVMR analysis revealed that all eight exposure factors were causally associated with depression; alcoholic drinks per week, sleeplessness or insomnia, BMI, mood swings, weekly usage of mobile phone in the last 3 months, and cooked vegetable intake were risk factors, and beef intake and "smoking status: never" were protection factors. Heterogeneity tests revealed no heterogeneity for alcoholic drinks per week, sleeplessness or insomnia, mood swings, weekly usage of mobile phone in the last 3 months, and cooked vegetable intake. Meanwhile, there was no horizontal pleiotropy in UVMR, and LOO analysis verified that univariable analysis results were reliable. Moreover, MVMR analysis indicated that mood swings and weekly usage of mobile phone in the last 3 months were risk factors, and beef intake was a protection factor for depression when multiple factors occurred at the same time. Conclusion: Alcoholic drinks per week, sleeplessness or insomnia, BMI, mood swings, weekly usage of mobile phone in the last 3 months, and cooked vegetable intake were risk factors, and beef intake and "smoking status: never" were protection factors. In addition, mood swings, weekly usage of mobile phone in the last 3 months, and beef intake had a direct effect on depression when multiple factors occurred simultaneously.

Simultaneous SERS Sensing of Cysteine and Homocysteine in Blood Based on the CBT-Cys Click Reaction: Toward Precisive Diagnosis of Schizophrenia.

At present, there is a lack of sufficiently specific laboratory diagnostic indicators for schizophrenia. Serum homocysteine (Hcy) levels have been found to be related to schizophrenia. Cysteine (Cys) is a demethylation product in the metabolism of Hcy, and they always coexist with highly similar structures in vivo. There are few reports on the use of Cys as a diagnostic biomarker for schizophrenia in collaboration with Hcy, mainly because the rapid, economical, accurate, and high-throughput simultaneous detection of Cys and Hcy in serum is highly challenging. Herein, a click reaction-based surface-enhanced Raman spectroscopy (SERS) sensor was developed for simultaneous and selective detection of Cys and Hcy. Through the efficient and specific CBT-Cys click reaction between the probe containing cyan benzothiazole and Cys/Hcy, the tiny methylene difference between the molecular structures of Cys and Hcy was converted into the difference between the ring skeletons of the corresponding products that could be identified by plasmonic silver nanoparticle enhanced molecular fingerprint spectroscopy to realize discriminative detection. Furthermore, the SERS sensor was successfully applied to the detection in related patient serum samples, and it was found that the combined analysis of Cys and Hcy can improve the diagnostic accuracy of schizophrenia compared to a single indicator.

Reprogramming of regulatory T cells in inflammatory tumor microenvironment: can it become immunotherapy turning point?

Overcoming the immunosuppressive tumor microenvironment and identifying widely used immunosuppressants with minimal side effects are two major challenges currently hampering cancer immunotherapy. Regulatory T cells (Tregs) are present in almost all cancer tissues and play an important role in preserving autoimmune tolerance and tissue homeostasis. The tumor inflammatory microenvironment causes the reprogramming of Tregs, resulting in the conversion of Tregs to immunosuppressive phenotypes. This process ultimately facilitates tumor immune escape or tumor progression. However, current systemic Treg depletion therapies may lead to severe autoimmune toxicity. Therefore, it is crucial to understand the mechanism of Treg reprogramming and develop immunotherapies that selectively target Tregs within tumors. This article provides a comprehensive review of the potential mechanisms involved in Treg cell reprogramming and explores the application of Treg cell immunotherapy. The interference with reprogramming pathways has shown promise in reducing the number of tumor-associated Tregs or impairing their function during immunotherapy, thereby improving anti-tumor immune responses. Furthermore, a deeper understanding of the mechanisms that drive Treg cell reprogramming could reveal new molecular targets for future treatments.

Mediating Effect of Tobacco Dependence on the Association Between Maternal Smoking During Pregnancy and Chronic Obstructive Pulmonary Disease: Case-Control Study.

BACKGROUND: Maternal smoking during pregnancy (MSDP) is a known risk factor for offspring developing chronic obstructive pulmonary disease (COPD), but the underlying mechanism remains unclear. OBJECTIVE: This study aimed to explore whether the increased COPD risk associated with MSDP could be attributed to tobacco dependence (TD). METHODS: This case-control study used data from the nationwide cross-sectional China Pulmonary Health study, with controls matched for age, sex, and smoking status. TD was defined as smoking within 30 minutes of waking, and the severity of TD was assessed using the Fagerstrom Test for Nicotine Dependence. COPD was diagnosed when the ratio of forced expiratory volume in 1 second to forced vital capacity was <0.7 in a postbronchodilator pulmonary function test according to the 2017 Global Initiative for Chronic Obstructive Lung Disease criteria. Logistic regression was used to examine the correlation between MSDP and COPD, adjusting for age, sex, BMI, educational attainment, place of residence, ethnic background, occupation, childhood passive smoking, residential fine particulate matter, history of childhood pneumonia or bronchitis, average annual household income, and medical history (coronary heart disease, hypertension, and diabetes). Mediation analysis examined TD as a potential mediator in the link between MSDP and COPD risk. The significance of the indirect effect was assessed through 1000 iterations of the "bootstrap" method. RESULTS: The study included 5943 participants (2991 with COPD and 2952 controls). Mothers of the COPD group had higher pregnancy smoking rates (COPD: n=305, 10.20%; controls: n=211, 7.10%; P<.001). TD was more prevalent in the COPD group (COPD: n=582, 40.40%; controls: n=478, 33.90%; P<.001). After adjusting for covariates, MSDP had a significant effect on COPD (ß=.097; P<.001). There was an association between MSDP and TD (ß=.074; P<.001) as well as between TD and COPD (ß=.048; P=.007). Mediation analysis of TD in the MSDP-COPD association showed significant direct and indirect effects (direct: ß=.094; P<.001 and indirect: ß=.004; P=.03). The indirect effect remains present in the smoking population (direct: ß=.120; P<.001 and indirect: ß=.002; P=.03). CONCLUSIONS: This study highlighted the potential association between MSDP and the risk of COPD in offspring, revealing the mediating role of TD in this association. These findings contribute to a deeper understanding of the impact of prenatal tobacco exposure on lung health, laying the groundwork for the development of relevant prevention and treatment strategies.

Oxygen-Independent Synchronized ROS Generation and Hypoxia Prodrug Activation with Z-Scheme Heterostructure Sonosensitizer.

Combination therapy has emerged as a promising approach for effective tumor treatment. However, the combination of sonodynamic therapy (SDT) and hypoxia-activated prodrugs (HAPs) has not been explored due to the contradictory requirement of oxygen (O2 ) for reactive oxygen species (ROS) generation and the necessity to avoid O2 for the activation of HAPs. In this study, this challenge is addressed by developing BiOCl-Au-Ag2 S Z-scheme heterostructure nanoparticles loaded with tirapazamine (TPZ) to achieve O2 -independent therapy. These nanoparticles demonstrate efficient electron-hole separation under ultrasound irradiation while maintaining a high redox potential. The generated holes react with water to efficiently produce hydroxyl radicals, while the electrons autonomously activate TPZ, negating the need for O2 . In vitro and in vivo assessments validate the effective tumor elimination by these Z-scheme nanoparticles without disrupting the hypoxic environment. This innovative design overcomes the limitations associated with O2 requirement in SDT and introduces a novel strategy for HAP activation and synergistic therapy between ROS and HAPs-based therapy.

Intelligent Size-Switchable Iron Carbide-Based Nanocapsules with Cascade Delivery Capacity for Hyperthermia-Enhanced Deep Tumor Ferroptosis.

The ferroptosis pathway is recognized as an essential strategy for tumor treatment. However, killing tumor cells in deep tumor regions with ferroptosis agents is still challenging because of distinct size requirements for intratumoral accumulation and deep tumor penetration. Herein, intelligent nanocapsules with size-switchable capability that responds to acid/hyperthermia stimulation to achieve deep tumor ferroptosis are developed. These nanocapsules are constructed using poly(lactic-co-glycolic) acid and Pluronic F127 as carrier materials, with Au-Fe2 C Janus nanoparticles serving as photothermal and ferroptosis agents, and sorafenib (SRF) as the ferroptosis enhancer. The PFP@Au-Fe2 C-SRF nanocapsules, designed with an appropriate size, exhibit superior intratumoral accumulation compared to free Au-Fe2 C nanoparticles, as evidenced by photoacoustic and magnetic resonance imaging. These nanocapsules can degrade within the acidic tumor microenvironment when subjected to laser irradiation, releasing free Au-Fe2 C nanoparticles. This enables them to penetrate deep into tumor regions and disrupt intracellular redox balance. Under the guidance of imaging, these PFP@Au-Fe2 C-SRF nanocapsules effectively inhibit tumor growth when exposed to laser irradiation, capitalizing on the synergistic photothermal and ferroptosis effects. This study presents an intelligent formulation based on iron carbide for achieving deep tumor ferroptosis through size-switchable cascade delivery, thereby advancing the comprehension of ferroptosis in the context of tumor theranostics.

A 4D Printed Adhesive, Thermo-Contractile, and Degradable Hydrogel for Diabetic Wound Healing.

Chronic wound healing remains a substantial clinical challenge. Current treatments are often either prohibitively expensive or insufficient in meeting the various requirements needed for effective diabetic wound healing. A 4D printing multifunctional hydrogel dressing is reported here, which aligns perfectly with wounds owning various complex shapes and depths, promoting both wound closure and tissue regeneration. The hydrogel is prepared via digital light process (DLP) 3D printing of the mixture containing N-isopropylacrylamide (NIPAm), curcumin-loaded Pluronic F127 micelles (Cur-PF127), and poly(ethylene glycol) diacrylate-dopamine (PEGDA575-Do), a degradable crosslinker. The use of PEGDA575-Do ensures tissue adhesion and degradability, and cur-PF127 serves as an antibacterial agent. Moreover, the thermo-responsive mainchains (i.e., polymerized NIPAm) enables the activation of wound contraction by body temperature. The features of the prepared hydrogel, including robust tissue adhesion, temperature-responsive contraction, effective hemostasis, spectral antibacterial, biocompatibility, biodegradability, and inflammation regulation, contribute to accelerating diabetic wound healing in Methicillin-resistant Staphylococcus aureus (MRSA)-infected full-thickness skin defect diabetic rat models and liver injury mouse models, highlighting the potential of this customizable, mechanobiological, and inflammation-regulatory dressing to expedite wound healing in various clinical settings.

Toxicity and chemical characterization of shale gas wastewater discharged to the receiving water: Evidence from toxicity identification evaluation.

Flowback and produced water (FPW) generated from shale gas extraction is a complex mixture consisting of injected drilling fluid, deep formation water, and byproducts of downhole reactions. Limited knowledge is available regarding the impact of discharged FPW on surface water in China. With the development of shale gas exploitation, this emphasizes an urgent need for comprehensive assessments and stringent regulations to ensure the safe disposal of shale gas extraction-related wastewater. Herein, we explored potential impacts of treated shale gas wastewater discharged into a local river in southwest China through toxicity identification evaluation (TIE). Results revealed that organics and particulates significantly contributed to the overall toxicity of the treated FPW wastewater. Through target and suspect chemical analyses, various categories of organic contaminants were detected, including alkanes, aromatic hydrocarbons, biocides, phenols, and phthalates. Furthermore, non-target analysis uncovered the presence of surfactant-related contaminants in tissues of exposed organisms, but their contribution to the observed toxicity was unclear due to the lack of effect data for these compounds. Higher toxicity was found at the discharge point compared with upstream sites; however, the toxicity was rapidly mitigated due to dilution in the receiving river, posing little impact on downstream areas. Our study highlighted the importance of monitoring toxicity and water quality of FPW effluent even though dilution could be a viable approach when the water volume in the discharge was small.

Effectiveness evaluation of autotransplanted teeth after performing extraoral endodontic surgery instead of conventional root canal therapy.

PURPOSE: The aim of this study was to examine the viability and efficacy of utilizing extraoral apicoectomy and retrograde filling in combination to seal the root canal system of mature molars without the need for root canal therapy (RCT) during the autotransplantation of teeth (ATT). MATERIALS AND METHODS: This study screened 27 patients who received ATT at the Department of Oral Surgery in the Hospital of Stomatology from 2019 to 2021. Extraoral apicoectomy and retrograde filling were performed, while RCT was temporarily not performed. The study analysed the periodontal status and masticatory function of transplanted teeth one to three years postoperation and used cone-beam computed tomography (CBCT) and periapical radiograph (PA) to evaluate the integrity of the periodontal space and intra/periapical inflammation. The potential predictors of survival/success were analysed statistically. We also conducted questionnaires and chewing efficiency tests. RESULTS: In this study, 27 TTs from 27 patients were found to be fully functional in terms of chewing ability. The overall survival rate was 100% (27/27), and the success rate was 70.4% (19/27). A total of 90.9% (20/22) of patients reported being satisfied or very satisfied with their TTs. Additionally, the chewing efficiency of the transplantation side was on average 82.0% of that of the healthy side, with a significant difference between the two sides (P < 0.05). None of the potential predictors were found to significantly affect the success or survival of the transplanted tooth (TT). CONCLUSION: The combination of extraoral apicoectomy and retrograde filling in TT showed promising outcomes, but further clinical cases and longer follow-up times are still required to validate the treatment plan.

Nomogram for predicting early complications after distal gastrectomy.

BACKGROUND: Reducing or preventing postoperative morbidity in patients with gastric cancer (GC) is particularly important in perioperative treatment plans. AIM: To identify risk factors for early postoperative complications of GC post-distal gastrectomy and to establish a nomogram prediction model. METHODS: This retrospective study included 131 patients with GC who underwent distal gastrectomy at the Second Hospital of Shandong University between January 2019 and February 2023. The factors influencing the development of complications after distal gastrectomy in these patients were evaluated using univariate and multivariate logistic regression analysis. Based on the results obtained, a predictive nomogram was established. The nomogram was validated using internal and external (n = 45) datasets. Its sensitivity and specificity were established by receiver operating characteristic curve analysis. Decision curve (DCA) analysis was used to determine its clinical benefit and ten-fold overfitting was used to establish its accuracy and stability. RESULTS: Multivariate logistic regression analysis showed that hypertension, diabetes, history of abdominal surgery, and perioperative blood transfusion were independent predictors of postoperative complications of distal gastrectomy. The modeling and validation sets showed that the area under the curve was 0.843 [95% confidence interval (CI): 0.746-0.940] and 0.877 (95%CI: 0.719-1.000), the sensitivity was 0.762 and 0.778, respectively, and the specificity was 0.809 and 0.944, respectively, indicating that the model had good sensitivity and specificity. The C-indexes of the modeling and validation datasets were 0.843 (95%CI: 0.746-0.940) and 0.877 (95%CI: 0.719-1.000), respectively. The calibration curve (Hosmer Lemeshow test: χ2 = 7.33) showed that the model had good consistency. The results of the DCA analysis indicated that this model offered good clinical benefits. The accuracy of 10-fold cross-validation was 0.878, indicating that the model had good accuracy and stability. CONCLUSION: The nomogram prediction model based on independent risk factors related to postoperative complications of distal gastrectomy can facilitate perioperative intervention for high-risk populations and reduce the incidence of postoperative complications.

Gut microbiome: decision-makers in the microenvironment of colorectal cancer.

Colorectal cancer (CRC) is a common malignancy of the gastrointestinal tract, accounting for the second most common cause of gastrointestinal tumors. As one of the intestinal barriers, gut bacteria form biofilm, participate in intestinal work, and form the living environment of intestinal cells. Metagenomic next-generation sequencing (mNGS) of the gut bacteria in a large number of CRC patients has been established, enabling specific microbial signatures to be associated with colorectal adenomato-carcinoma. Gut bacteria are involved in both benign precursor lesions (polyps), in situ growth and metastasis of CRC. Therefore, the term tumorigenic bacteria was proposed in 2018, such as Escherichia coli, Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis, etc. Meanwhile, bacteria toxins (such as cytolethal distending toxin (CDT), Colibactin (Clb), B. fragilis toxin) affect the tumor microenvironment and promote cancer occurrence and tumor immune escape. It is important to note that there are differences in the bacteria of different types of CRC. In this paper, the role of tumorigenic bacteria in the polyp-cancer transformation and the effects of their secreted toxins on the tumor microenvironment will be discussed, thereby further exploring new ideas for the prevention and treatment of CRC.

Oxidative stress and autophagy-mediated immune patterns and tumor microenvironment infiltration characterization in gastric cancer.

Recent years have seen a sharp rise in the amount of research on the connection between oxidative stress, autophagy, and cancer cells. However, the significant functions of oxidative stress and autophagy-related genes (OARGs) in gastric cancer (GC) are yet to be investigated integrally. Therefore, it will be a new and promising concept to search for novel OARG-related biomarkers to predict the prognosis and treatment response of GC. First, we assessed changes in prognosis and tumor microenvironment (TME) characteristics across the various oxidative stress and autophagy-related modification patterns based on a detailed analysis of 17 OARGs with prognostic significance of 808 GC samples. We identified three distinct OARG alteration patterns which displayed unique biological characteristics and immune cell infiltration features. Using principal component analysis methods, the OARGscore was developed to evaluate the OARG modification patterns of certain tumors. The negative connection between OARGscore and immune cells was statistically significant. Increased survival, a higher incidence of mutations, and a better response to immunotherapy were all predicted to be related to patients' high-OARGscore. In addition, the candidate chemotherapeutic drugs were predicted using the oncoPredict program. The low-OARGscore group was predicted to benefit more from Ribociclib, Alisertib, Niraparib, Epirubicin, Olaparib, and Axitinib, while patients in the high-OARGscore group were predicted to benefit more from Afatinib, Oxaliplatin, Paclitaxel, 5-Fluorouracil, Dabrafenib and Lapatinib. Our findings offer a specific method for predicting a patient's prognosis and susceptibility to immunotherapy, as well as a promising insight of oxidative stress and autophagy in GC.

Identifying endoplasmic reticulum stress-related molecular subtypes and prognostic model for predicting the immune landscape and therapy response in pancreatic cancer.

Endoplasmic reticulum stress (ERS) is caused by the accumulation of intracellular misfolded or unfolded proteins and is associated with cancer development. In this study, pan-cancer analysis revealed complex genetic variations, including copy number variation, methylation, and somatic mutations for ERS-related genes (ERGs) in 33 kinds of cancer. Consensus clustering divided pancreatic cancer (PC) patients from TCGA and GEO databases into two ERS-related subtypes: ERGcluster A and B. Compared with ERGcluster A, ERGcluster B had a more active ERS state and worse prognosis. Subsequently, the ERS-related prognostic model was established to quantify the ERS score for a single sample. The patient with a low ERS score had remarkably longer survival times. ssGSEA and CIBERSORT algorithms revealed that activated B cells and CD8+ T cells had higher infiltration in the low ERS score group, but higher infiltration of activated CD4+ T cells, activated dendritic cells, macrophages, and neutrophils in the high ERS score group. Drug sensitivity analysis indicated the low ERS score group had a better response to gemcitabine, paclitaxel, 5-fluorouracil, oxaliplatin, and irinotecan. RT-qPCR validated that MET, MUC16, and KRT7 in the model had higher expression levels in pancreatic tumour tissues. Single-cell analysis further revealed that MET, MUC16, and KRT7 were mainly expressed in cancer cells in PC tumour microenvironment. In all, we first constructed the ERS-related molecular subtypes and prognostic model in PC. Our research highlighted the vital role of ERS in PC and contributed to further research on molecular mechanisms and novel therapeutic strategies for PC in the future.

A Nanozymatic-Mediated Smartphone Colorimetric Sensing Platform for the Detection of Dimethyl Phthalate (DMP) and Dibutyl Phthalate (DBP).

Plasticizers are a type of toxic substance that may remain in food, posing significant health risks including carcinogenic, teratogenic, mutagenic, and other adverse effects. In this study, a novel strategy was employed by combining Pt@Au nanozymes with high catalytic properties to created two catalytic signal probes, designated as Pt@Au@Ab1 and Pt@Au@Ab2, specifically designed for the detection of dimethyl phthalate (DMP) and dibutyl phthalate (DBP). These catalytic signal probes served as the foundation for the development of a colorimetric immunoassay, enabling the simultaneous detection of both DMP and DBP. The colorimetric immunoassay is capable of detecting DMP in the range of 0.5-100 µg/L with a limit of detection as low as 0.1 µg/L and DBP in the range of 1-32 µg/L with a low limit of detection of 0.5 µg/L. The developed immunoassay can be used for the determination of the DMP and DBP in baijiu and plastic bottled drinks. The recovery rate is in the range of 96.4% and 100.5% and the coefficient of variation is between 1.0% and 7.2%. This innovative colorimetric immunoassay offers a robust tool for the simultaneous quantification of DMP and DBP in real samples.

Impact of shale gas wastewater discharge on the trace elements of the receiving river in the Sichuan Basin, China.

The potential contamination of shale gas wastewater generated from hydraulic fracturing to water resources is of growing concern, yet minimum attention has been paid to the impact of shale gas wastewater on the trace elements of the receiving waters. In this study, we analyzed the levels of 50 trace elements of a river that receives effluent from a shale gas wastewater treatment facility in the Sichuan Basin, China. Sixteen trace elements were detected in the surface water sample from the effluent discharge site, all of which were of higher concentrations than the upstream background level. Among the 16 shale gas wastewater-related elements, Sr, Ba, and Li were of elevated levels in the downstream water samples (24.9-44.2%, 5.0-8.0 times, and 17.8-22.8 times higher than the upstream background level, respectively). Shale gas wastewater effluent may be related to the accumulation of Sr, Ba, Li, and Cs in riverbed sediments near and/or downstream of the effluent discharge site and may lead to elevated pollution level of Sr and Li in downstream sediments. The ecological risk of the riverbed sediments was of medium to high level, with Cd contributing to the most risk, while shale gas wastewater-related elements are of low potential risk throughout the river. Our results suggested that shale gas wastewater effluent discharge had limited impacts on the trace elements of the receiving river within two years.