Associations of serum arginine acid with sarcopenia in Chinese eldely women.

BACKGROUND: The prevalence of sarcopenia is increasing in worldwide with accelerated aging process. The high dietary protein intakes are associated with improved muscle mass and strength especially in Asian countries. However, there are few researches on amino acid levels or mechanism exploration. We conducted a case-control study to explore the amino acid metabolic characteristics and potential mechanism of elderly women with sarcopenia using targeted amino acid metabolomics approach combined with an analysis of dietary intake. METHODS: For our case-control study, we recruited women (65-75 y) from a Shanghai community with 50 patients with sarcopenia and 50 healthy controls. The consensus updated by the Asian Working Group on Sarcopenia in 2019 was used to screening for sarcopenia and control groups. We collected fasting blood samples and evaluated dietary intake. We used the amino acid-targeted metabolomics by ultra performance liquid chromatography tandem mass spectrometry to identify metabolic differentials between the case and control groups and significantly enriched metabolic pathways. RESULTS: The case (sarcopenia) group had a lower intake of energy, protein, and high-quality protein (P < 0.05) compared to the control (healthy) group. We identified four differential amino acids: arginine (P < 0.001) and cystine (P = 0.003) were lower, and taurine (P = 0.001) were higher in the case group. CONCLUSION: Low levels of arginine in elderly women are associated with a higher risk of sarcopenia.

Theoretical Study of Dissolved Gas Molecules in Transformer Oil Adsorbed on Intrinsic and TM (Ta, V)-Doped MoTe2 Monolayer.

In this paper, CH4, C2H2, H2, and CO adsorbed on intrinsic MoTe2 monolayer and transition metal atom (Ta, V)-doped MoTe2 monolayer have been investigated with density functional theory based on first-principles study. The adsorption energy, geometries, band structures, and density of states of four gases (CH4, C2H2, H2, and CO) adsorbed on the MoTe2 and doped MoTe2 surfaces were analyzed. The results shown that the gas adsorption performance of transition metal atom (Ta, V)-doped MoTe2 monolayers is more superior than that of intrinsic MoTe2, and the adsorption energy and charge transfer of the adsorbed gases on the TM-MoTe2 monolayer are significantly increased in comparison with both sides. Among them, Ta-MoTe2 has the largest Eads value in the adsorbed CO system with a very small adsorption distance, as well as a more suitable recovery time of CO at room temperature, so Ta-MoTe2 can be a candidate material for CO detection. New atoms were introduced during the doping process, which increased the carrier density and carrier mobility of the material, thus improving the charge transfer at the surface of the material. which provides a direction for the gas-sensitive properties of metal Ta-modified MoTe2 materials.

Causal relationship between immune cell phenotypes and risk of biliary tract cancer: evidence from Mendelian randomization analysis.

Background: Biliary tract cancer stands as a prevalent illness, posing significant risks to human health, where immune cells are pivotal in both its development and recovery processes. Due to the diverse functionalities exhibited by different immune cell phenotypes within the organism, and the relatively limited research on their relationship with biliary tract cancer, this study employed Mendelian randomization (MR) to explore their potential association, thereby aiding in a better understanding of the causal link between immune cell phenotypes and biliary tract cancer. Methods: In this study, the causative association of 731 immunophenotype with biliary tract cancer was established using publicly accessible genome-wide association study (GWAS) genetic data through two-sample MR analysis. Sensitivity analyses assess horizontal pleiotropy and heterogeneity of the study findings. Results: Among the 731 immunophenotypes examined, a total of 26 immune cell phenotypes were found to exhibit positive results, indicating a significant association with the risk of biliary tract cancer. We confirmed that among these 26 types of immune cells, there are primarily 13 types of B cells; three types of classical dendritic cells (CDCs), including CD80 on myeloid DC, HLA DR on myeloid DC, and Myeloid DC %DC; one type of mature stage T cell,CD4RA on TD CD4+; six types of regulatory T cells; and three types of myeloid cells.

Analysis of optical properties and response mechanism of H2S fluorescent probe based on rhodamine derivatives.

H2S plays a crucial role in numerous physiological and pathological processes. In this project, a new fluorescent probe, SG-H2S, for the detection of H2S, was developed by introducing the recognition group 2,4-dinitrophenyl ether. The combination of rhodamine derivatives can produce both colorimetric reactions and fluorescence reactions. Compared with the current H2S probes, the main advantages of SG-H2S are its wide pH range (5-9), fast response (30 min), and high selectivity in competitive species (including biological mercaptan). The probe SG-H2S has low cytotoxicity and has been successfully applied to imaging in MCF-7 cells, HeLa cells, and BALB/c nude mice. We hope that SG-H2S will provide a vital method for the field of biology.

WTAP participates in neuronal damage by protein translation of NLRP3 in an m6A-YTHDF1-dependent manner after traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a common complication of acute and severe neurosurgery. Remodeling of N6-methyladenosine (m6A) stabilization may be an attractive treatment option for neurological dysfunction after TBI. In the present study, the authors explored the epigenetic methylation of RNA-mediated NLRP3 inflammasome activation after TBI. METHODS: Neurological dysfunction, histopathology, and associated molecules were examined in conditional knockout (CKO) WTAP [flox/flox, Camk2a-cre] , WTAP flox/flox , and pAAV-U6-shRNA-YTHDF1-transfected mice. Primary neurons were used in vitro to further explore the molecular mechanisms of action of WTAP/YTHDF1 following neural damage. RESULTS: The authors found that WTAP and m6A levels were upregulated at an early stage after TBI, and conditional deletion of WTAP in neurons did not affect neurological function but promoted functional recovery after TBI. Conditional deletion of WTAP in neurons suppressed neuroinflammation at the TBI early phase: WTAP could directly act on NLRP3 mRNA, regulate NLRP3 mRNA m6A level, and promote NLRP3 expression after neuronal injury. Further investigation found that YTH domain of YTHDF1 could directly bind to NLRP3 mRNA and regulate NLRP3 protein expression. YTHDF1 mutation or silencing improved neuronal injury, inhibited Caspase-1 activation, and decreased IL-1ß levels. This effect was mediated via suppression of NLRP3 protein translation, which also reversed the stimulative effect of WTAP overexpression on NLRP3 expression and inflammation. CONCLUSIONS: Our results indicate that WTAP participates in neuronal damage by protein translation of NLRP3 in an m6A-YTHDF1-dependent manner after TBI and that WTAP/m6A/YTHDF1 downregulation therapeutics is a viable and promising approach for preserving neuronal function after TBI, which can provide support for targeted drug development.

Monocytes release cystatin F dimer to associate with Aß and aggravate amyloid pathology and cognitive deficits in Alzheimer's disease.

BACKGROUND: Understanding the molecular mechanisms of Alzheimer's disease (AD) has important clinical implications for guiding therapy. Impaired amyloid beta (Aß) clearance is critical in the pathogenesis of sporadic AD, and blood monocytes play an important role in Aß clearance in the periphery. However, the mechanism underlying the defective phagocytosis of Aß by monocytes in AD remains unclear. METHODS: Initially, we collected whole blood samples from sporadic AD patients and isolated the monocytes for RNA sequencing analysis. By establishing APP/PS1 transgenic model mice with monocyte-specific cystatin F overexpression, we assessed the influence of monocyte-derived cystatin F on AD development. We further used a nondenaturing gel to identify the structure of the secreted cystatin F in plasma. Flow cytometry, enzyme-linked immunosorbent assays and laser scanning confocal microscopy were used to analyse the internalization of Aß by monocytes. Pull down assays, bimolecular fluorescence complementation assays and total internal reflection fluorescence microscopy were used to determine the interactions and potential interactional amino acids between the cystatin F protein and Aß. Finally, the cystatin F protein was purified and injected via the tail vein into 5XFAD mice to assess AD pathology. RESULTS: Our results demonstrated that the expression of the cystatin F protein was specifically increased in the monocytes of AD patients. Monocyte-derived cystatin F increased Aß deposition and exacerbated cognitive deficits in APP/PS1 mice. Furthermore, secreted cystatin F in the plasma of AD patients has a dimeric structure that is closely related to clinical signs of AD. Moreover, we noted that the cystatin F dimer blocks the phagocytosis of Aß by monocytes. Mechanistically, the cystatin F dimer physically interacts with Aß to inhibit its recognition and internalization by monocytes through certain amino acid interactions between the cystatin F dimer and Aß. We found that high levels of the cystatin F dimer protein in blood contributed to amyloid pathology and cognitive deficits as a risk factor in 5XFAD mice. CONCLUSIONS: Our findings highlight that the cystatin F dimer plays a crucial role in regulating Aß metabolism via its peripheral clearance pathway, providing us with a potential biomarker for diagnosis and potential target for therapeutic intervention.

High fidelity detection of miRNAs from complex physiological samples through electrochemical nanosensors empowered by proximity catalysis and magnetic separation.

Electrochemical detection of miRNA biomarkers in complex physiological samples holds great promise for accurate evaluation of tumor burden in the perioperative period, yet limited by reproducibility and bias issues. Here, nanosensors installed with hybrid probes that responsively release catalytic DNAzymes (G-quadruplexes/hemin) were developed to solve the fidelity challenge in an immobilization-free detection. miRNA targets triggered toehold-mediated strand displacement reactions on the sensor surface and resulted in amplified shedding of DNAzymes. Subsequently, the interference background was removed by Fe3O4 core-facilitated magnetic separation. Binding aptamers of the electrochemical reporter (dopamine) were tethered closely to the catalytic units for boosting H2O2-mediated oxidation through proximity catalysis. The one-to-many conversion by dual amplification from biological-chemical catalysis facilitated sufficient homogeneous sensing signals on electrodes. Thereby, the nanosensor exhibited a low detection limit (2.08 fM), and high reproducibility (relative standard deviation of 1.99%). Most importantly, smaller variations (RSD of 0.51-1.04%) of quantified miRNAs were observed for detection from cell lysates, multiplexed detection from unprocessed serum, and successful discrimination of small upregulations in lysates of tumor tissue samples. The nanosensor showed superior diagnostic performance with an area under curve (AUC) of 0.97 and 94% accuracy in classifying breast cancer patients and healthy donors. These findings demonstrated the synergy of signal amplification and interference removal in achieving high-fidelity miRNA detection for practical clinical applications.

The causal relationship between gut microbiota and biliary tract cancer: comprehensive bidirectional Mendelian randomization analysis.

Background: Growing evidence has shown that gut microbiome composition is associated with Biliary tract cancer (BTC), but the causality remains unknown. This study aimed to explore the causal relationship between gut microbiota and BTC, conduct an appraisal of the gut microbiome's utility in facilitating the early diagnosis of BTC. Methods: We acquired the summary data for Genome-wide Association Studies (GWAS) pertaining to BTC (418 cases and 159,201 controls) from the Biobank Japan (BBJ) database. Additionally, the GWAS summary data relevant to gut microbiota (N = 18,340) were sourced from the MiBioGen consortium. The primary methodology employed for the analysis consisted of Inverse Variance Weighting (IVW). Evaluations for sensitivity were carried out through the utilization of multiple statistical techniques, encompassing Cochrane's Q test, the MR-Egger intercept evaluation, the global test of MR-PRESSO, and a leave-one-out methodological analysis. Ultimately, a reverse Mendelian Randomization analysis was conducted to assess the potential for reciprocal causality. Results: The outcomes derived from IVW substantiated that the presence of Family Streptococcaceae (OR = 0.44, P = 0.034), Family Veillonellaceae (OR = 0.46, P = 0.018), and Genus Dorea (OR = 0.29, P = 0.041) exerted a protective influence against BTC. Conversely, Class Lentisphaeria (OR = 2.21, P = 0.017), Genus Lachnospiraceae FCS020 Group (OR = 2.30, P = 0.013), and Order Victivallales (OR = 2.21, P = 0.017) were associated with an adverse impact. To assess any reverse causal effect, we used BTC as the exposure and the gut microbiota as the outcome, and this analysis revealed associations between BTC and five different types of gut microbiota. The sensitivity analysis disclosed an absence of empirical indicators for either heterogeneity or pleiotropy. Conclusion: This investigation represents the inaugural identification of indicative data supporting either beneficial or detrimental causal relationships between gut microbiota and the risk of BTC, as determined through the utilization of MR methodologies. These outcomes could hold significance for the formulation of individualized therapeutic strategies aimed at BTC prevention and survival enhancement.

Effects of glycated serum protein, homocysteine, and cystatin-C levels on pregnancy outcomes in patients with gestational diabetes mellitus.

Objective: To explore the effects of serum glycated serum protein (GSP), homocysteine (Hcy) and cystatin-C (Cys-C) levels on pregnancy outcomes in patients with gestational diabetes mellitus (GDM). Methods: Retrospective selection of 247 pregnant women who underwent normal prenatal examinations in The Yan'an People's Hospital from January 2020 to May 2022 were included in this retrospective study. Among them, 119 were pregnant women with diabetes (GDM-group) and 128 were pregnant women with normal blood glucose (Normal-group). The levels of serum GSP, HCY, CYS-C, and incidence of adverse pregnancy outcomes were compared between the two groups. The clinical value of levels of serum GSP, Hcy, and Cys-C in predicting adverse pregnancy outcomes were analyzed. Results: Compared with the Normal-group, the overall incidence of adverse pregnancy outcomes, serum GSP, Hcy, and Cys-C levels in the GDM-group were significantly higher (p<0.05). Logistic regression analysis showed that the levels of GSP, Hcy, and Cys-C were independent risk factors for adverse pregnancy outcomes in the GDM-group (p<0.05). Receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) for diagnosing adverse pregnancy outcomes in pregnant women with GDM using serum GSP, Hcy, and CysC levels alone were 0.817, 0.843, and 0.775, respectively. The AUC of the three indicators combined was 0.921, indicating that this combination has a good predictive value for diagnosing adverse outcomes in GDM-complicated pregnancies. Conclusions: GDM is associated with a high risk of adverse pregnancy outcomes. Levels of serum GSP, Hcy, and Cys-C are higher in patients with GDM. The higher the levels of GSP, Hcy, and Cys-C, the greater the risk of adverse pregnancy outcomes. Combining these three indicators can effectively predict maternal pregnancy outcomes.

Causal relationship between gut microbiota and risk of esophageal cancer: evidence from Mendelian randomization study.

BACKGROUND: The causative implications remain ambiguous. Consequently, this study aims to evaluate the putative causal relationship between gut microbiota and Esophageal cancer (EC). METHODS: The genome-wide association study (GWAS) pertaining to the microbiome, derived from the MiBioGen consortium-which consolidates 18,340 samples across 24 population-based cohorts-was utilized as the exposure dataset. Employing the GWAS summary statistics specific to EC patients sourced from the GWAS Catalog and leveraging the two-sample Mendelian randomization (MR) methodology, the principal analytical method applied was the inverse variance weighted (IVW) technique. Cochran's Q statistic was utilized to discern heterogeneity inherent in the data set. Subsequently, a reverse MR analysis was executed. RESULTS: Findings derived from the IVW technique elucidated that the Family Porphyromonadaceae (P = 0.048) and Genus Candidatus Soleaferrea (P = 0.048) function as deterrents against EC development. In contrast, the Genus Catenibacterium (P = 0.044), Genus Eubacterium coprostanoligenes group (P = 0.038), Genus Marvinbryantia (P = 0.049), Genus Ruminococcaceae UCG010 (P = 0.034), Genus Ruminococcus1 (P = 0.047), and Genus Sutterella (P = 0.012) emerged as prospective risk contributors for EC. To assess reverse causal effect, we used EC as the exposure and the gut microbiota as the outcome, and this analysis revealed associations between EC and seven different types of gut microbiota. The robustness of the MR findings was substantiated through comprehensive heterogeneity and pleiotropy evaluations. CONCLUSIONS: This research identified certain microbial taxa as either protective or detrimental elements for EC, potentially offering valuable biomarkers for asymptomatic diagnosis and prospective therapeutic interventions for EC.

Mechanism of sturgeon intestinal inflammation induced by Yersinia ruckeri and the effect of florfenicol intervention.

The mechanism by which Y. ruckeri infection induces enteritis in Chinese sturgeon remains unclear, and the efficacy of drug prevention and control measures is not only poor but also plagued with numerous issues. We conducted transcriptomic and 16 S rRNA sequencing analyses to examine the differences in the intestinal tract of hybrid sturgeon before and after Y. ruckeri infection and florfenicol intervention. Our findings revealed that Y. ruckeri induced the expression of multiple inflammatory factors, including il1ß, il6, and various chemokines, as well as casp3, casp8, and multiple tumor necrosis factor family members, resulting in pathological injury to the body. Additionally, at the phylum level, the relative abundance of Firmicutes and Bacteroidota increased, while the abundance of Plesiomonas and Cetobacterium decreased at the genus level, altering the composition of the intestinal flora. Following florfenicol intervention, the expression of multiple apoptosis and inflammation-related genes was down-regulated, promoting tissue repair. However, the flora became further dysregulated, increasing the risk of infection. In conclusion, our analysis of the transcriptome and intestinal microbial composition demonstrated that Y. ruckeri induces intestinal pathological damage by triggering apoptosis and altering the composition of the intestinal microbiota. Florfenicol intervention can repair pathological damage, but it also exacerbates flora imbalance, leading to a higher risk of infection. These findings help elucidate the molecular mechanism of Y. ruckeri-induced enteritis in sturgeon and evaluate the therapeutic effect of drugs on intestinal inflammation in sturgeon.

Metabolic syndrome and risk of colorectal cancer: A Mendelian randomization study.

Background: Observational studies have previously demonstrated a significant relationship among both metabolic syndrome (Mets) and colorectal cancer (CRC). Whether there is a causal link remains controversial. Objective: To clarify whether Mets and their components have a causal effect on colorectal cancer, we have carried out a bidirectional Mendelian randomization analysis (MR). Methods: This study started from genome-wide association data for Mets and its 5 components (hypertension, waist circumference, fasting blood glucose, serum triglycerides, and serum high-density lipoprotein cholesterol) and colorectal cancer. Mendelian randomization (MR) techniques were used in the study to examine their associations. Results: After Benjamini-Hochberg multiple corrections, genetically predicted significant causal link exists between WC (waist circumference) and CRC. The OR was 1.35 (95 % CI: 1.08-1.69; p = 0.0096). Other Mets components (HBP, FBG, TG, HDL), on the other hand, found no evidence of a genetic link between CRC and Mets. In addition, MR results showed that CRC was not causally related to either Mets or the components. We get the same result in the validated dataset. Conclusion: According to the bidirectional MR investigation shows a significant causal relationship among obesity and CRC in the Mets component but no causal relationship in the opposite direction.

Impact of early heparin therapy on outcomes in patients with solid malignancy associated sepsis: a marginal structural model causal analyse.

Background: Previous studies documented that heparin can inhibit the invasion and metastasis of tumors, but its role on outcomes in patients with solid malignancy complicated sepsis remains unclear. Methods: A retrospective cohort study was conducted in critically ill patients with solid malignancy associated sepsis from the Medical Information Mart for Intensive Care (MIMIC)-IV database. The primary endpoint was intensive care unit (ICU) mortality, secondary outcomes were thrombosis and hospital mortality. Propensity score matching (PSM), marginal structural Cox model (MSCM), cox proportional hazards model, stratification analysis and E-value were used to account for baseline differences, time-varying confounding and unmeasured variables. Results: A total of 1,512 patients with solid malignancy complicated sepsis were enrolled, of which 683 in the heparin group with intensive care unit mortality, thrombosis rate and hospital mortality were 9.7%, 5.4%, 16.1%, and 829 in the non-heparin group with ICU mortality, thrombosis rate and hospital mortality were 14.6%, 12.5%, 22.6%. Similar results were observed on outcomes for patients with PSM (ICU mortality hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.41-0.92), thrombosis rate (HR 0.42, 95% confidence interval 0.26-0.68); hospital mortality HR 0.70, 95% CI 0.50-0.99). marginal structural Cox model further reinforced the efficacy of heparin in reducing ICU mortality (HR 0.48, 95% CI 0.34-0.68). Logistic regression and Cox regression model showed heparin use also markedly reduced thrombosis (HR 0.42; 95% CI 0.26-0.68; p < 0.001) and hospital mortality (HR 0.70; 95% CI 0.50-0.99; p = 0.043). Stratification analysis with the MSCM showed an effect only those with digestive system cancer (HR 0.33, 95% CI 0.16-0.69). Conclusion: Early heparin therapy improved outcomes in critically ill patients with solid malignancy complicated sepsis. These results are evident especially in those with digestive system cancer. A prospective randomized controlled study should be designed to further assess the relevant findings.

Static electric field (SEF) exposure promotes the proliferation of B lymphocytes.

With the rapid development of ultra-high voltage direct current (UHV DC) transmission technology, the intensity of electric fields in the surrounding environment of UHV DC transmission lines significantly increased, which raised public concerns about the potential health effects of electric fields. Previous studies have shown that the exposure of electromagnetic field was associated with cancer. B lymphocytes can produce autoantibodies and tumor growth factors through proliferation, which contributes to the development of cancer. Therefore, this study explored the effect and mechanism of static electric field (SEF) generated by DC transmission lines on the proliferation levels of B lymphocytes. Male mice were exposed to SEF. After the exposure of 7 and 14 days, the proliferation levels of B lymphocytes in the spleens of mice were measured, respectively. To validate biological effect discovered in animal experiments and elucidate the mechanism of the effect from the perspective of signaling pathways, lymphocytes were exposed to SEF. After the exposure of 24, 48 or 72 h, the proliferation levels of B lymphocytes, the expression levels of key proteins and cell cycle were determined. This study found that SEF exposure activated NF-κB pathway by stimulating ERK1/2 pathway and promoted B lymphocytes to enter S phase from G0/G1 phase. Meanwhile, SEF exposure also promoted B lymphocytes to enter G2 phase. Namely, SEF exposure significantly promoted the proliferation of B lymphocytes. This discovery provided theoretical and practical support for the prevention or application of negative or positive effects caused by SEF exposure and provided directions for future research.

Multiple forms of cell death: A focus on the PI3K/AKT pathway.

Cell death is a natural biological process that occurs in living organisms. Since 1963, extensive research has shed light on the occurrence, progress, and final outcome of cell death. According to different cell phenotypes, it is classified into different types, including apoptosis, pyroptosis, necroptosis, autophagy, ferroptosis, cuproptosis, and so on. However, regardless of the form of cell death, what we ultimately expect is the disappearance of abnormal cells, such as tumor cells, while normal cells survive. As a result, it is vital to investigate the details of cell death, including death triggers, potent regulators, and executioners. Although significant progress has been made in understanding molecular pathways of cell death, many aspects remain unclear because of the complex regulatory networks in cells. Among them, the phosphoinositide-3-kinase (PI3K)/protein kinase B(AKT) pathway is discovered to be a crucial regulator of the cell death process. AKT, as a proto-oncogene, has become a major focus of attention in the medical community due to its role in regulating a multiplicity of cellular functions counting metabolism, immunity, proliferation, survival, transcription, and protein synthesis. Here, we explored the connection between the PI3K/AKT pathway and cell death, aiming to enhance our comprehension of the mechanism underlying this process. Such knowledge may pave the way for the subsequent development of more effective disease treatments, such as finding suitable targets for drug intervention.

A harsh environment resistant robust Co(OH)2@stearic acid nanocellulose-based membrane for oil-water separation and wastewater purification.

Traditional membranes are inefficient in treating highly toxic organic pollutants and oily wastewater in harsh environments, which is difficult to meet the growing demand for green development. Herein, the Co(OH)2@stearic acid nanocellulose-based membrane was prepared by depositing Co(OH)2 on the nanocellulose-based membrane (NBM) through chemical soaking method, which enables efficient oil/water mixtures separation and degradation of pollutants by photocatalysis in harsh environments. The Co(OH)2@stearic acid nanocellulose-based membrane (Co(OH)2@stearic acid NBM) shows good photocatalytic degradation performance for methylene blue pollutants in harsh environment, and has significant degradation rate (93.66%). At the same time, the Co(OH)2@stearic acid NBM with superhydrophobicity and superoleophilicity also exhibits respectable oil/water mixtures separation performance (n-Hexane, dimethyl carbonate, chloroform and toluene) under harsh environment (strong acid/strong alkali), which has an excellent oil-water mixtures separation flux of 87 L·m-2·h-1 (n-Hexane/water) and oil-water mixture separation efficiency of over 93% (n-Hexane/water). In addition, this robust Co(OH)2@stearic acid NBM shows good self-cleaning and recycling performance. Even though seven oil-water separation tests have been carried out under harsh environment, it can still maintain respectable oil-water mixture separation rate and flux. The multifunctional membrane has excellent resistance to harsh environments, oil-water separation and pollutant degradation can be performed even in harsh environments, which provides a convenient way to treat sewage under harsh conditions efficiently and has great potential in practical application.

A prognostic model based on the COL1A1-network in gastric cancer.

BACKGROUND: Gastric cancer (GC) is one of the most common malignancies worldwide with a poor prognosis due to the lack of early detection and effective treatments. As a biomarker, collagen type I alpha 1 (COL1A1) is often dysregulated in some cancer types. However, the expression profile of COL1A1 and functional mechanism in GC is still unclear. METHODS: To screen for the different expression genes of GC vs. adjacent tissues, an RNA-seq dataset containing 30 clinical samples and multi-omics datasets of 478 samples were obtained from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, respectively. Then the functional enrichment analysis and survival analysis of dysregulated genes were performed. Furthermore, through constructing the protein-protein interactive network, the function mode of COL1A1 was studied. Finally, a prognostic model was built by least absolute shrinkage and selection operator (LASSO) Cox algorithm to assess the clinical value of COL1A1-network. RESULTS: Firstly, a total of 89 different expression genes (58 down-regulated and 31 up-regulated) that appeared simultaneously in both GEO and TCGA datasets were detected and enriched in some functions regarding the extracellular matrix. However, only 12 genes were significantly correlative with overall survival of GC patients. Among them, ASPN, COL1A1, COL12A1, FNDC1, INHBA and MMP12 could form a network that might activate the epithelial-mesenchymal transition (EMT) pathway. Meanwhile, a prognostic model containing ASPN and INHBA was able to divide GC patients into 2 groups with different risks and predict 5-years survival accurately (AUC = 0.732, 95% CI (0.619, 0.845)). CONCLUSION: COL1A1 is up-regulated in GC and may result in a poor prognosis with a higher mRNA level. Moreover, the COL1A1-network may promote malignant metastasis via EMT pathway activation and act as a prognostic marker.

Flower-like Nanozyme with Highly Porous Carbon Matrix Induces Robust Oxidative Storm against Drug-Resistant Cancer.

Reactive oxygen species (ROS) generators are sparking breakthroughs in sensitization and treatment of therapy-resistant tumors, yet the efficacy is drastically compromised by limited substrate concentrations, short lifetimes of free radicals, and restricted oxidative damage. Herein, a flower-like nanozyme with highly permeable leaflets accommodating catalytic metal sites was developed to address the challenges by boosting substrate and product accessibility. In the formation of a zeolite imidazole framework, cobalt ions promoted catalytic polymerization and deposition of polydopamine. The polymers acted as a stiffener for preventing framework collapse and maneuvering pore reopening during carbonization. The cobalt single-atom/cluster sites in the highly porous matrix generated peroxidase/oxidase-like activities with high catalytic efficiency (Kcat/Km) up to 6 orders of magnitude greater than that of conventional nano-/biozymes. Thereby, a robust ROS storm induced by selective catalysis led to rapid accumulation of oxidative damage and failure of antioxidant and antiapoptotic defense synchronization in drug-resistant cancer cells. By synergy of a redox homeostasis disrupter co-delivered, a significantly high antitumor efficiency was realized in vivo. This work offers a route to kinetically favorable ROS generators for advancing the treatment of therapy-resistant tumors.

Emerging glyco-risk prediction model to forecast response to immune checkpoint inhibitors in colorectal cancer.

BACKGROUND: Aberrant glycosylation is one of the most common post-translational modifications leading to heterogeneity in colorectal cancer (CRC). This study aims to construct a risk prediction model based on glycosyltransferase to forecast the response to immune checkpoint inhibitors in CRC patients. METHODS: Based on the TCGA dataset and glycosyltransferase genes, the NMF algorithm and WGCNA were used to identify molecular subtypes and co-expressed genes, respectively. Lasso and multivariate COX regression were used to identify prognostic glycosyltransferase genes and construct a glyco-risk prediction model in CRC patients. Univariate and multivariate Cox regression, Kaplan-Meier, and ROC curves were applied to further verify the prognostic performance of the model in CRC patients in the training and validation sets. We compared the responsiveness of immunotherapy and chemotherapy between the two groups. In vitro experiments and clinical specimens verified the specific function of the key glycosyltransferase genes in CRC. RESULTS: The CRC cohort was divided into two subtypes with prominent differences in survival based on the well-robust seven-gene glyco-risk prediction model (composed of ALG1L2, HAS1, PYGL, COLGALT2, B3GNT4, POFUT2, and GALNT7). The nomograms based on the risk model could predict the prognosis of CRC patients independently of other clinicopathologic characteristics. Our prediction model showed a better overall prediction performance than other models. Compared with the low-risk group, the high-risk CRC patients showed a lower immune infiltration state, but a higher TMB and a lower response to anti-PD-1, anti-PD-L1, and anti-CTLA-4 therapy. Clinical specimen validation showed an obvious difference in the expression of seven glycosyltransferase genes between the low- and high-risk groups. Significant reduction in POFUT2 expression in high-risk groups was associated with reduced N-glycans production. CONCLUSION: Our study constructed a robust glyco-risk prediction model that could provide direction for immunotherapy and chemotherapy in CRC patients, which could help clinicians make personalized treatment decisions.

The role of transient receptor potential channels in metastasis.

Metastasis is the hallmark of failed tumor treatment and is typically associated with death due to cancer. Transient receptor potential (TRP) channels affect changes in intracellular calcium concentrations and participate at every stage of metastasis. Further, they increase the migratory ability of tumor cells, promote angiogenesis, regulate immune function, and promote the growth of tumor cells through changes in gene expression and function. In this review, we explore the potential mechanisms of action of TRP channels, summarize their role in tumor metastasis, compile inhibitors of TRP channels relevant in tumors, and discuss current challenges in research on TRP channels involved in tumor metastasis.