The prognostic significance and potential mechanism of DBF4 zinc finger in hepatocellular carcinoma.

DBF4 zinc finger (DBF4) is a critical component involved in DNA replication and cell proliferation. It acts as a positive regulator of the cell division cycle 7 kinase. In this study, our investigation encompassed the impact of DBF4 on hepatocellular carcinoma (HCC) progression and delved into the potential mechanisms. We utilized open-access databases like TCGA and GEO to analyze the association between DBF4 and 33 different tumor types. We also conducted immunohistochemistry experiments to validate the expression of DBF4 in HCC, STAD, COAD, READ, PAAD, and LGG. Furthermore, we employed lentiviral transduction to knockdown DBF4 in HLF and SMMC cells, as well as to overexpress DBF4 in Huh7 cells. Subsequently, we evaluated the impact of DBF4 on proliferation, migration, and invasion of hepatocellular carcinoma cells. RNA sequencing and KEGG pathway enrichment analysis were also conducted to identify potential pathways, which were further validated through WB experiments. Finally, pathway inhibitor was utilized in rescue experiments to confirm whether DBF4 exerts its effects on tumor cells via the implicated pathway. Our findings revealed that DBF4 exhibited significant expression levels in nearly all examined tumors, which were further substantiated by the results of immunohistochemistry analysis. High DBF4 expression was correlated with poor overall survival (OS), disease-specific survival (DSS), progression-free interval (PFI), disease-free interval (DFI), relapse-free interval (RFI) in majority of tumor types, particularly in patients with HCC. In vitro experiments demonstrated that inhibition of DBF4 impaired the proliferative, migratory, and invasive abilities of HCC cells, whereas overexpression of DBF4 promoted these phenotypes. Sequencing results indicated that DBF4 may induce these changes through the ERBB signaling pathway. Further experimental validation revealed that DBF4 activates the ERBB signaling pathway, leading to alterations in the JNK/STAT, MAPK, and PI3K/AKT signaling pathways, thereby impacting the proliferative, migratory, and invasive abilities of tumor cells. Lastly, treatment of Huh7 cells overexpressing DBF4 with the ERBB2 inhibitor dacomitinib demonstrated the ability of ERBB2 inhibition to reverse the promoting effect of DBF4 overexpression on the proliferative, migratory, and invasive abilities of HCC cells. DBF4 plays a pivotal oncogenic role in HCC by promoting the ERBB signaling pathway and activating its downstream PI3K/AKT, JNK/STAT3, and MAPK signaling pathways. DBF4 may serve as a prognostic biomarker for patients with HCC.

Pan-immune inflammation value as a prognostic biomarker for cancer patients treated with immune checkpoint inhibitors.

Background: Immune checkpoint inhibitors (ICIs) represent a paradigm shift in the development of cancer therapy. However, the improved efficacy of ICIs remains to be further investigated. We conducted a systematic review and meta-analysis to evaluate the pan-immunoinflammatory value (PIV) and PILE score used to predict response to ICI therapy. Methods: We searched selected databases for studies on pan-immune inflammation values and their association with outcomes of treatment with immune checkpoint inhibitors. We used hazard ratios (HRS) and 95% confidence intervals (CI) to summarize survival outcomes. All data analyses were performed using STATA 15.0. Results: 7 studies comprising 982 patients were included in the meta-analysis. The pooled results showed that higher PIV was significantly associated with shorter overall survival OS (HR = 1.895, 95%CI: 1.548-2.318) and progression-free survival (PFS) (HR = 1.582, 95%CI: 1.324-1.890). Subgroup analyses also confirmed the reliability of the results. Conclusions: High PIV and PILE metrics are associated with lower survival in cancer patients receiving ICIs.

Identification of a potential signature to predict the risk of postmenopausal osteoporosis.

BACKGROUND: Postmenopausal osteoporosis (PMOP) is related to the elevated risk of fracture in postmenopausal women. Thus, to effectively predict the occurrence of PMOP, we explored a novel gene signature for the prediction of PMOP risk. METHODS: The WGCNA analysis was conducted to identify the PMOP-related gene modules based on the data from GEO database (GSE56116 and GSE100609). The "limma" R package was applied for screening differentially expressed genes (DEGs) based on the data from GSE100609 dataset. Next, LASSO Cox algorithm were applied to identify valuable PMOP-related risk genes and construct a risk score model. GSEA was then conducted to analyze potential signaling pathways between high-risk (HR) score and low-risk (LR) score groups. RESULTS: A novel risk model with five PMOP-related risk genes (SCUBE3, TNNC1, SPON1, SEPT12 and ULBP1) was developed for predicting PMOP risk status. RT-qPCR and western blot assays validated that compared to postmenopausal non-osteoporosis (non-PMOP) patients, SCUBE3, ULBP1, SEPT12 levels were obviously elevated, and TNNC1 and SPON1 levels were reduced in blood samples from PMOP patients. Additionally, PMOP-related pathways such as MAPK signaling pathway, PI3K-Akt signaling pathway and HIF-1 signaling pathway were significantly activated in the HR-score group compared to the LR-score group. The circRNA-gene-miRNA and gene-transcription factor networks showed that 533 miRNAs, 13 circRNAs and 40 TFs might be involved in regulating the expression level of these five PMOP-related genes. CONCLUSION: Collectively, we developed a PMOP-related gene signature based on SCUBE3, TNNC1, SPON1, SEPT12 and ULBP1 genes, and higher risk score indicated higher risk suffering from PMOP.

Prognostic value of body composition on survival outcomes in melanoma patients receiving immunotherapy.

Objective: The influence of body composition on the effectiveness of immune checkpoint inhibitors (ICIs) in patients with melanoma is still uncertain in clinical practice. Therefore, the objective of this study was to examine the potential association between body composition and clinical outcomes in patients with melanoma undergoing ICIs treatment. Methods: A systematic literature search was performed across several databases, including PubMed, Embase, Cochrane Library and Google Scholar, to gather relevant studies. The primary outcomes of interest were overall survival (OS) and progression-free survival (PFS), assessed by hazard ratios (HR). Secondary outcomes, such as adverse events (AE), were evaluated using odds ratios (OR). Results: This meta-analysis comprised ten articles involving a total of 1,283 patients. Systemic analysis of all collected evidence revealed that body composition, including low skeletal muscle index (SMI) (OS: HR = 1.66, 95% CI = 1.13-2.43, p = 0.010; PFS: HR = 1.28, 95% CI = 1.06-1.55, p = 0.009), high subcutaneous adipose tissue density (SMD) (OS: HR = 1.93, 95% CI = 1.09-3.44, p = 0.025; PFS: HR = 1.31, 95% CI = 1.06-1.63, p = 0.012), and sarcopenia (OS: HR = 1.25, 95% CI = 1.03-1.51, p = 0.022; PFS: HR = 1.25, 95% CI = 1.03-1.51, p = 0.022), were significantly associated with OS and PFS in melanoma patients treated with ICIs. However, these markers did not show a significant association with treatment-related adverse events. Interestingly, no significant correlation was found between visceral fat index (VFI) (OS: HR = 0.71, 95% CI = 0.29-1.76, p = 0.462; PFS: HR = 0.98, 95% CI = 0.93-1.02, p = 0.274) and OS or PFS in melanoma patients under ICIs treatment. Conclusion: Body composition was found to be associated with decreased treatment response and lower long-term efficacy in patients with melanoma undergoing immune checkpoint inhibitor (ICI) therapy. However, it is important to note that body composition did not appear to contribute to increased incidence of adverse events in these patients.

Role of gonadally synthesized steroid hormones in the colorectal cancer microenvironment.

Objective: To understand the relationship between steroid hormones synthesized by the gonads and colorectal cancer as well as its tumor microenvironment, in the expectation of providing new ideas in order to detect and treat colorectal cancer. Methods: Through reviewing the relevant literature at home and abroad, we summarized that androgens promote the growth of colorectal cancer, and estrogens and progesterone help prevent bowel cancer from developing; these three hormones also have a relevant role in the cellular and other non-cellular components of the tumor microenvironment of colorectal cancer. Conclusion: The current literature suggests that androgens, estrogens, and progesterone are valuable in diagnosing and treating colorectal cancer, and that androgens promote the growth of colorectal cancer whereas estrogens and progesterone inhibit colorectal cancer, and that, in addition, the receptors associated with them are implicated in the modulation of a variety of cellular components of the microenvironment of colorectal cancer.

Low geriatric nutritional risk index as a poor prognostic biomarker for immune checkpoint inhibitor treatment in solid cancer.

Objective: In this investigation, we focused on the geriatric nutritional risk index (GNRI), a comprehensive metric that takes into account the patient's ideal weight, actual weight, and serum albumin levels to measure malnutrition. Our primary objective was to examine the predictive value of GNRI-defined malnutrition in determining the response to immunotherapy among cancer patients. Methods: Relevant articles for this study were systematically searched in PubMed, the Cochrane Library, EMBASE, and Google Scholar up to July 2023. Our analysis evaluated overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) as clinical outcomes. Results: This analysis comprised a total of eleven articles encompassing 1,417 patients. The pooled results revealed that cancer patients with low GNRI levels exhibited shorter OS (HR: 2.64, 95% CI: 2.08-3.36, p < 0.001) and PFS (HR: 1.87, 95% CI: 1.46-2.41, p < 0.001), and lower ORR (OR: 0.46, 95% CI: 0.33-0.65, p < 0.001) and DCR (OR: 0.42, 95% CI: 0.29-0.61, p < 0.001). Sensitivity analyses confirmed that the above results were stable. Egger's and Begg's tests revealed that there was no publication bias in the above results. Conclusion: Our results imply that the GNRI is a useful predictor of immunotherapy response in cancer patients.

High intramuscular adipose tissue content associated with prognosis and postoperative complications of cancers.

Sarcopenia has been considered an adverse prognostic factor in cancer patients. Intramuscular adipose tissue content, as a new marker of sarcopenia, can effectively reflect skeletal muscle quality. The aim of this study was performed to evaluate the association between high intramuscular adipose tissue content (IMAC) and survival outcomes and postoperative complications in cancer patients. Specific databases, including the Web of Science, Embase and Web of Science, were systematically searched to identify relevant articles evaluating the prognostic value of IMAC in cancer patients. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were utilized for comprehensive analysis. All data analyses were performed using STATA 12.0 software. A total of 25 studies from 24 articles including 5663 patients were enrolled in the study. Meta-analysis showed that high IMAC was associated with unfavourable overall survival (OS) (HR: 2.21, 95% CI: 1.70-2.86, P < 0.001), relapse-free survival (RFS) (HR: 1.51, 95% CI: 1.30-1.75, P < 0.001) and disease-specific survival (DSS) (HR: 1.64, 95% CI: 1.19-2.28, P = 0.003). Subgroup analysis revealed that high IMAC remained an adverse prognostic factor when stratified by different country, treatment methods, cancer type or analysis type. High IMAC had better predictive value for gallbladder carcinoma (GBC) (HR: 3.50, 95% CI: 1.98-6.17, P < 0.001), hepatocellular carcinoma (HCC) (HR: 1.84, 95% CI: 1.45-2.33, P < 0.001), pancreatic cancer (PC) (HR: 2.11, 95% CI: 1.67-2.66, P < 0.001) and colorectal cancer (CRC) (HR: 2.54, 95% CI: 1.27-5.10, P = 0.009). High IMAC was also identified as a significant risk factor for postoperative complications (OR: 2.05, 95% CI: 1.22-3.46, P = 0.007). High IMAC was associated with an adverse prognosis and an increased risk of postoperative complications in cancer patients. IMAC may be a good indicator of sarcopenia.

Photodynamic Therapy for Inflammatory and Cancerous Diseases of the Intestines: Molecular Mechanisms and Prospects for Application.

Photodynamic therapy (PDT) is a minimally invasive treatment that effectively targets cancer and inflammatory diseases. It has gained recognition for its efficacy, low toxicity, and potential for repeated use. Colorectal cancer (CRC) and inflammatory bowel diseases (IBD), including Crohn's disease (CD), and ulcerative colitis (UC), impose a significant burden on global intestinal health, with increasing incidence and prevalence rates. PDT shows promise as an emerging approach for gastrointestinal disease treatment, particularly IBD and CRC. Extensive preclinical research has demonstrated the safety and effectiveness of PDT for IBD and CRC, while clinical studies are currently underway. This review provides an overview of the underlying mechanisms responsible for the anti-inflammatory and anti-tumor effects of PDT, offering insights into the clinical application of PDT in IBD and CRC treatment. It is expected that this review will serve as a valuable reference for future research on PDT for CRC and IBD, contributing to advancements in the treatment of inflammatory and cancerous diseases of the intestines.

Prognostic value of controlling nutritional status on clinical and survival outcomes in cancer patients treated with immunotherapy.

Cancer is a leading cause of death globally. Immunotherapy has shown promise in treating various types of cancer, but its effectiveness varies among patients. The Controlling Nutritional Status (CONUT) score has been linked to the prognosis of different cancers. However, its predictive value for immunotherapy outcomes is not well understood. Our research represents the pioneering meta-study to examine the prognostic value of the CONUT score on cancer patients treated with an immune checkpoint inhibitor (ICI). A comprehensive literature search was conducted using various databases including PubMed, the Cochrane Library, EMBASE, and Google Scholar. The study was conducted until July 28, 2023. This analysis encompassed a comprehensive evaluation of various clinical outcomes, namely overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). 663 patients from 8 studies were included in this study. It showed that cancer patients with high CONUT score had poorer OS (HR: 1.94, 95% CI, 1.52-2.47, p < 0.001) and PFS (HR: 2.22, 95% CI, 1.48-3.31, p < 0.001), as well as worse ORR (OR: 0.46, 95% CI, 0.25-0.85, p = 0.013) and DCR (HR: 0.29, 95% CI, 0.14-0.59, p = 0.001). The CONUT score can predict the prognosis of tumor patients treated with ICIs.

Prognostic nutritional index as a prognostic biomarker for gastrointestinal cancer patients treated with immune checkpoint inhibitors.

Objective: Our study represents the first meta-analysis conducted to evaluate the prognostic utility of the baseline prognostic nutritional index (PNI) in patients with gastrointestinal cancer (GIC) who received immune checkpoint inhibitor (ICI) therapy. Methods: We searched PubMed, the Cochrane Library, EMBASE, and Google Scholar until April 23, 2023, to obtain relevant articles for this study. Our analysis examined several clinical outcomes, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Results: In this analysis, a total of 17 articles with 2883 patients were included. Our pooled results indicated that patients with high PNI levels had longer OS (HR: 0.530, 95% CI: 0.456-0.616, p < 0.001) and PFS (HR: 0.740, 95% CI: 0.649-0.844, p < 0.001), as well as higher ORR (OR: 1.622, 95% CI: 1.251-2.103, p < 0.004) and DCR (OR: 1.846, 95% CI: 1.428-2.388, p < 0.001). Subgroup analysis showed that PNI cutoff values of 40 to 45 showed greater predictive potential. Subgroup analysis also confirmed that the above findings still hold true in patients with esophageal cancer, gastric cancer, and hepatocellular carcinomas. Conclusion: The PNI were reliable predictors of outcomes in GIC patients treated with ICIs.

Effect of C7-T1 Extensional Posterior Transpedicle Osteotomy on Mobility and Quality of Life in Patients with Ankylosing Spondylitis Complicated with Lumbar Kyphosis and Related Factors.

Objective: To analyze the effect of C7-T1 extensional posterior transpedicular vertebral osteotomy (PSO) on mobility and quality of life in patients with ankylosing spondylitis (AS) and lumbar kyphosis. Methods: This study was conducted from February 2019 to February 2021 and a total of 38 patients with AS combined with kyphosis from Tianjin Union Medical Center, Tianjin, China, were selected for the study. After performing all preoperative examinations, all patients were treated with C7-T1 extensional posterior PSO osteotomy. The patients' operation and follow-up, pain degree as a Visual analogue scale (VAS) score and sagittal balance index changes before and after surgery, spinal function measured as; Bath Ankylosing Spondylitis Functional Index (BASFI) score and quality of life by Scoliosis Research Society-22 (SRS-22) score, were observed before and after surgery. Pearson correlation coefficient was used to analyze the correlation between patients' quality of life and BASFI score. Results: After surgery, the pain of the patients' back was significantly relieved, the patients' appearance and trunk balance function were significantly improved, and the symptoms related to nerve function were not significantly aggravated. No complications such as infection, internal fixation failure or spinal decompensation occurred in all patients. VAS score, kyphosis Cobb Angle and Sagittal Vertical Axis (SVA) of all patients showed P < .05 before and 1 year after surgery. BASFI score 1 year after surgery decreased significantly than that before surgery (P < .05). 1 year after surgery, body function, pain symptoms, self-image and psychological state of the patients were significantly improved, and the SRS-22 total score of the patients 1 year after surgery increased significantly than before surgery (P < 0.05). BASFI score was negatively correlated with SRS-22 score by Pearson correlation coefficient analysis (P < .05). Conclusion: C7-T1 extensional posterior PSO osteotomy has a good effect in the treatment of AS patients with lumbar kyphosis. The sagittal balance was well-restored with improvement in patients' quality of life after surgery, which makes C7-T1 osteotomy worthy of clinical application to treat patients suffering from AS combined with lumbar kyphosis.

Interaction between hydrophobic chitosan derivative and asphaltene in heavy oil to reduce viscosity of heavy oil.

The high viscosity of heavy oil made it difficult to exploit and transport heavy oil in pipeline. In this research, N-[(2-hydroxy-3-trimethylammonium) propyl] O-stearoyl chitosan tetraphenylboride (sc-CTS-st) was synthesized from chitosan, 2, 3-epoxy-propyl trimethyl ammonium chloride, sodium tetraphenylboron and stearyl chloride. sc-CTS-st contains long chain saturated aliphatic hydrocarbon, hydroxyl group and benzene ring, which could be dissolved in heavy oil fully and interacted with asphaltene. At 50 °C, the viscosity of heavy oil could be reduced to 13,800 mPa·s at most, with a viscosity reduction rate of 57.54 %. SEM and XRD showed that sc-CTS-st could affect the supramolecular accumulation structure of asphaltenes. Using FT-IR, sc-CTS-st could interact with asphaltene in the form of hydrogen bonds using the polar parts of the molecule, thereby weakening the self-association between asphaltene molecules. Molecular simulation was used to demonstrate the interaction mechanism between chitosan derivatives and asphaltenes. sc-CTS-st interacted with asphaltene through chemical bonding and influenced the self-association of asphaltene molecules. In addition, the non-polar portion of sc-CTS-st molecules could form a coating on the outside of the asphaltenes stacking structure, thus shielding or reducing the polarity of the stacking structure surface.

Investigating causal associations among gut microbiota, metabolites, and liver diseases: a Mendelian randomization study.

Objective: There is some evidence for an association between gut microbiota and nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), and viral hepatitis, but no studies have explored their causal relationship. Methods: Instrumental variables of the gut microbiota (N = 13266) and gut microbiota-derived metabolites (N = 7824) were acquired, and a Mendelian randomization study was performed to explore their influence on NAFLD (1483 European cases and 17,781 European controls), ALD (2513 European cases and 332,951 European controls), and viral hepatitis risk (1971 European cases and 340,528 European controls). The main method for examining causality is inverse variance weighting (IVW). Results: IVW results confirmed that Anaerotruncus (p = 0.0249), Intestinimonas (p = 0.0237), Lachnoclostridium (p = 0.0245), Lachnospiraceae NC2004 group (p = 0.0083), Olsenella (p = 0.0163), and Peptococcus (p = 0.0472) were protective factors for NAFLD, and Ruminococcus 1 (p = 0.0120) was detrimental for NAFLD. The higher abundance of three genera, Lachnospira (p = 0.0388), Desulfovibrio (p = 0.0252), and Ruminococcus torques group (p = 0.0364), was correlated with a lower risk of ALD, while Ruminococcaceae UCG 002 level was associated with a higher risk of ALD (p = 0.0371). The Alistipes (p = 0.0069) and Ruminococcaceae NK4A214 group (p = 0.0195) were related to a higher risk of viral hepatitis. Besides, alanine (p = 0.0076) and phenyllactate (p = 0.0100) were found to be negatively correlated with NAFLD, while stachydrine (Op = 0.0244) was found to be positively associated with NAFLD. The phenylacetate (p = 0.0353) and ursodeoxycholate (p = 0.0144) had a protective effect on ALD, while the threonate (p = 0.0370) exerted a detrimental influence on ALD. The IVW estimates of alanine (p = 0.0408) and cholate (p = 0.0293) showed their suggestive harmful effects against viral hepatitis, while threonate (p = 0.0401) displayed its suggestive protective effect against viral hepatitis. Conclusion: In conclusion, our research supported causal links between the gut microbiome and its metabolites and NAFLD, ALD, and viral hepatitis.

Construction of a T-cell exhaustion-related gene signature for predicting prognosis and immune response in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a heterogeneous malignancy with a rising prevalence worldwide. Immunotherapy has been shown to improve treatment outcomes for HCC. We aimed to construct a T-cell exhaustion-related gene prognostic model (TEXPM) for HCC and to elucidate the immunologic characteristics and advantages of immunotherapy in T-cell exhaustion-Related Gene-defined HCC groups. METHODS: Single-cell RNA sequencing data were used in conjunction with TCGA Differentially expressed genes (DEGs) to screen for T-cell exhaustion-Related Genes (TEXGs) for subsequent evaluation. Using univariate Cox regression analysis and LASSO regression analysis, five genes (FTL, GZMA, CD14, NPC2, and IER3) were subsequently selected for the construction of a TEXPM. Then, we evaluated the immunologic characteristics and advantages of immunotherapy in groups identified by TEXPM. RESULTS: The TEXPM was formed with FTL, GZMA, CD14, NPC2, and IER3. The results of the training and validation team studies were consistent, with the low TEXPM group surviving longer than the high TEXPM group (P < 0.001). Multivariate Cox regression analysis demonstrated that TEXPM (HR: 2.347, 95%CI: 1.844-2.987; HR: 2.172, 95% CI: 1.689-2.793) was an independent prognostic variable for HCC patients. The low-TEXPM group was linked to active immunity, less aggressive phenotypes, strong infiltration of CD8+ T cells, CD4 + T cells, and M1 macrophages, and a better response to ICI treatment. A high TEXPM group, on the other hand, was associated with suppressive immunity, more aggressive phenotypes, a significant infiltration of B cells, M0 macrophages, and M2 macrophages, and a reduced response to ICI treatment. FTL is an independent prognostic variable in HCC patients and the knockdown of FTL can affect the biological behavior of hepatocellular carcinoma cells. CONCLUSIONS: TEXPM is a promising prognostic biomarker connected to the immune system. Differentiating immunological and molecular features and predicting patient outcomes may be facilitated by TEXPM grouping. Furthermore, the expression of FTL was found to be an independent prognostic factor for HCC. Knockdown of FTL significantly inhibited proliferation, migration, and invasive activity in liver cancer cells.

Downregulation of Bmal1 Expression in Celiac Ganglia Protects against Hepatic Ischemia-Reperfusion Injury.

Hepatic ischemia-reperfusion injury (HIRI) significantly contributes to liver dysfunction following liver transplantation and hepatectomy. However, the role of the celiac ganglion (CG) in HIRI remains unclear. Adeno-associated virus was used to silence Bmal1 expression in the CG of twelve beagles that were randomly assigned to the Bmal1 knockdown group (KO-Bmal1) and the control group. After four weeks, a canine HIRI model was established, and CG, liver tissue, and serum samples were collected for analysis. The virus significantly downregulated Bmal1 expression in the CG. Immunofluorescence staining confirmed a lower proportion of c-fos+ and NGF+ neurons in TH+ cells in the KO-Bmal1 group than in the control group. The KO-Bmal1 group exhibited lower Suzuki scores and serum ALT and AST levels than the control group. Bmal1 knockdown significantly reduced liver fat reserve, hepatocyte apoptosis, and liver fibrosis, and it increased liver glycogen accumulation. We also observed that Bmal1 downregulation inhibited the hepatic neurotransmitter norepinephrine, neuropeptide Y levels, and sympathetic nerve activity in HIRI. Finally, we confirmed that decreased Bmal1 expression in CG reduces TNF-α, IL-1ß, and MDA levels and increases GSH levels in the liver. The downregulation of Bmal1 expression in CG suppresses neural activity and improves hepatocyte injury in the beagle model after HIRI.

Uridine Inhibits Hepatocellular Carcinoma Cell Development by Inducing Ferroptosis.

Uridine is a key metabolite used as a substrate for the production of DNA, RNA, and glucose, and it is mainly synthesized in the liver. Currently, it is not known whether uridine levels are altered in the tumor microenvironment of patients with hepatocellular carcinoma (HCC) and whether uridine can be a target for tumor therapy. In this study, the detection of genes associated with de novo uridine synthesis, carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, dihydroorotase (CAD) (n = 115), and dihydroorotate dehydrogenase (DHODH) (n = 115) in HCC tissues through tissue microarrays revealed that the expression of CAD and DHODH was higher in tumor compared with paraneoplastic tissues. Next, we collected tumor tissues from surgically resected HCC patients and the corresponding adjacent non-tumor tissues (n = 46) for LC-MS/MS assays. The results showed that the median and interquartile ranges of uridine content in non-tumor and tumor tissues were 640.36 (504.45-807.43) and 484.22 (311.91-626.73) nmol/g, respectively. These results suggest that uridine metabolism is disturbed in HCC patients. To further investigate whether uridine can be used as a tumor-therapeutic target, a series of high concentrations of uridine were incubated with HCC cells in vitro and in vivo. It was observed that uridine dose-dependently inhibited the proliferation, invasion, and migration of HCC cells by activating the ferroptosis pathway. Overall, these results reveal for the first time the range of uridine content in human HCC tissues and suggest that uridine may be a new target for HCC therapy.

Synergy of Single Atoms and Lewis Acid Sites for Efficient and Selective Lignin Disassembly into Monolignol Derivatives.

Lignin is the most abundant aromatic polymer from the natural and renewable lignocellulosic biomass resource. Developing highly efficient catalysts for lignin depolymerization to produce valuable monophenols with high yield and selectivity remains a desirable but challenging target in this field. Here, we design a synergistic catalyst combining atomically dispersed Mo centers and Al Lewis acid sites on a MgO substrate (Mo1Al/MgO) for the depolymerization of Eucalyptus lignin via the ß-aryl ether bond cleavage. A near-theoretical monophenol yield of 46% with an ultrahigh selectivity of 92% for coniferyl and sinapyl methyl ether, as well as good cycling durability, was achieved simultaneously by Mo1Al/MgO in an inert N2 atmosphere. First-principles calculations and control catalytic experiments confirmed the synergistic catalysis mechanism between Mo1-O5 single-atom centers and the neighboring Al Lewis acid sites with the participation of a methanol solvent. This study validates the feasibility of designing better-performing catalysts with synergistic multiactive sites for the efficient and selective disassembly of complex renewable biopolymers into highly value-added products with lower cost and greater security.

Effects of hormones on intestinal stem cells.

The maintenance of intestinal renewal and repair mainly depends on intestinal stem cells (ISCs), which can also contribute to the growth of intestinal tumours. Hormones, which are vital signalling agents in the body, have various effects on the growth and replacement of intestinal stem cells. This review summarises recent progress in the identification of hormones associated with intestinal stem cells. Several hormones, including thyroid hormone, glucagon-like peptide-2, androgens, insulin, leptin, growth hormone, corticotropin-releasing hormone and progastrin, promote the development of intestinal stem cells. However, somatostatin and melatonin are two hormones that prevent the proliferation of intestinal stem cells. Therefore, new therapeutic targets for the diagnosis and treatment of intestinal illnesses can be identified by examining the impact of hormones on intestinal stem cells.

Competitive Coordination-Oriented Monodispersed Cobalt Sites on a N-Rich Porous Carbon Microsphere Catalyst for High-Performance Zn-Air Batteries.

Metal/nitrogen-doped carbon single-atom catalysts (M-N-C SACs) show excellent catalytic performance with a maximum atom utilization and customizable tunable electronic structure. However, precisely modulating the M-Nx coordination in M-N-C SACs remains a grand challenge. Here, we used a N-rich nucleobase coordination self-assembly strategy to precisely regulate the dispersion of metal atoms by controlling the metal ratio. Meanwhile, the elimination of Zn during pyrolysis produced porous carbon microspheres with a specific surface area of up to 1151 m2 g-1, allowing maximum exposure of Co-N4 sites and facilitating charge transport in the oxygen reduction reaction (ORR) process. Thereby, the monodispersed cobalt sites (Co-N4) in N-rich (18.49 at%) porous carbon microspheres (CoSA/N-PCMS) displayed excellent ORR activity under alkaline conditions. Simultaneously, the Zn-air battery (ZAB) assembled with CoSA/N-PCMS outperformed Pt/C+RuO2-based ZABs in terms of power density and capacity, proving that they have good prospects for practical application.

The Use of Antibiotics During Immune Checkpoint Inhibitor Treatment Is Associated with Lower Survival in Advanced Esophagogastric Cancer.

OBJECTIVE: Immune checkpoint inhibitors (ICI) are effective in only a minority of patients with esophagogastric cancer (EGC). Here, we aimed to explore the impact of antibiotic use on outcomes in ICI-treated EGC patients. METHODS: Patients with advanced EGC treated with ICIs at our center were identified between 2017 and 2021. The impact of antibiotic use on overall survival (OS) and progression-free survival (PFS) was assessed by a log-rank test. Eligible articles were retrieved using PubMed, the Cochrane Library, EMBASE, and Google Scholar by December 17, 2022. Clinical outcomes were OS, PFS, and disease control rate (DCR). RESULTS: In our cohort, 85 EGC patients were recruited. The results showed that antibiotic use significantly shortens OS (HR: 1.91, 95% CI: 1.11-3.28, P = 0.020) and PFS (HR: 2.13, 95% CI: 1.21-3.74, P = 0.009) and reduces DCR (OR: 0.27, 95% CI: 0.10-0.720, P = 0.013) in EGC patients treated with ICIs. The meta-analysis results revealed that antibiotic use was significantly associated with worse OS (HR = 2.454, 95% CI: 1.608-3.748, P < 0.001), PFS (HR = 2.539, 95% CI: 1.455-4.432, P = 0.001), and lower DCR (OR = 0.246, 95% CI: 0.105-0.577, P = 0.001). No publication bias existed, and sensitivity analysis confirmed stable results. CONCLUSION: In patients with advanced EGC undergoing ICI, the use of antibiotics, such as cephalosporins, was associated with inferior survival rates.