Cancer Stemness Online: A Resource for Investigating Cancer Stemness and Associations with Immune Response.

Cancer progression involves the gradual loss of a differentiated phenotype and the acquisition of progenitor and stem-cell-like features, which are potential culprits of immunotherapy resistance. Although the state-of-art predictive computational methods have facilitated the prediction of cancer stemness, currently there is no efficient resource that can meet various usage requirements. Here, we present the Cancer Stemness Online, an integrated resource for efficiently scoring cancer stemness potential at the bulk and single-cell levels. The resource integrates 8 robust predictive algorithms as well as 27 signature gene sets associated with cancer stemness for predicting stemness scores. Downstream analyses were performed from five different aspects, including identifying the signature genes of cancer stemness, exploring the associations with cancer hallmarks, cellular states, the immune response, and communication with immune cells; investigating the contributions to patient survival; and performing a robustness analysis of cancer stemness among different methods. Moreover, the pre-calculated cancer stemness atlas for more than 40 cancer types can be accessed by users. Both the tables and diverse visualizations of the analytical results are available for download. Together, Cancer Stemness Online is a powerful resource for scoring cancer stemness and expanding the downstream functional interpretation, including immune response as well as cancer hallmarks. Cancer Stemness Online is freely accessible at http://bio-bigdata.hrbmu.edu.cn/CancerStemnessOnline.

CanCellVar: A database for single-cell variants map in human cancer.

Numerous variants, including both single-nucleotide variants (SNVs) in DNA and A>G RNA edits in mRNA as essential drivers of cellular proliferation and tumorigenesis, are commonly associated with cancer progression and growth. Thus, mining and summarizing single-cell variants will provide a refined and higher-resolution view of cancer and further contribute to precision medicine. Here, we established a database, CanCellVar, which aims to provide and visualize the comprehensive atlas of single-cell variants in tumor microenvironment. The current CanCellVar identified ∼3 million variants (∼1.4 million SNVs and ∼1.4 million A>G RNA edits) involved in 2,754,531 cells of 5 major cell types across 37 cancer types. CanCellVar provides the basic annotation information as well as cellular and molecular function properties of variants. In addition, the clinical relevance of variants can be obtained including tumor grade, treatment, metastasis, and others. Several flexible tools were also developed to aid retrieval and to analyze cell-cell interactions, gene expression, cell-development trajectories, regulation, and molecular structure affected by variants. Collectively, CanCellVar will serve as a valuable resource for investigating the functions and characteristics of single-cell variations and their roles in human tumor evolution and treatment.

Highly Effective Pyroelectric Catalysis for Simultaneous Tumor-Targeted Dynamic Therapy and Gentle Photothermal Therapy by Oxygen-Vacancy-Rich CeO2-BaTiO3 Nanorods.

Pyroelectric nanostructures can effectively generate temperature-mediated reactive oxygen species (ROS) through the pyroelectric effect, providing promise for treating hypoxic tumors; and therefore, the synergistic application of photothermal therapy (PTT) and pyroelectric dynamic therapy (PEDT) presents an intriguing approach for cancer therapy. However, this method still faces challenges in improving pyroelectric catalysis and achieving precise tumor localization. In this study, a nano-heterojunction based on CeO2-BaTiO3 nanorods (IR1061@PCBNR) is reported, which exhibits highly effective pyroelectric catalysis for simultaneous tumor-targeted dynamic therapy and gentle photothermal therapy through the utilization of the rich oxygen vacancies. The oxygen vacancies create active sites that facilitate the migration of pyroelectrically-induced charge carriers, improving charge separation and ROS generation. IR1061@PCBNR also demonstrates high tumor penetration; while, minimizing damage to normal cells. This precise nanomedicine strategy holds great potential for advancing dynamic cancer therapies by overcoming the limitations of conventional approaches.

The death risk of pediatric patients with cancer-related sepsis requiring continuous renal replacement therapy: a retrospective cohort study.

OBJECTIVE: To assess the outcome of patients with cancer-related sepsis requiring continuous renal replacement therapy (CRRT) in a single-center pediatric intensive care unit (PICU). METHOD: Children with sepsis who necessitate CRRT from January 2017 to December 2021 were enrolled. The patients with leukemia/lymphoma or solid tumors were defined as underlying cancer. Multivariate logistic regression analysis was performed to identify the death risk factors in patients with cancer-related sepsis. RESULTS: A total of 146 patients were qualified for inclusion. Forty-six (31.5%) patients with cancer-related sepsis and 100 (68.5%) non-cancer-related sepsis. The overall PICU mortality was 28.1% (41/146), and mortality was significantly higher in cancer-related sepsis patients compared with non-cancer patients (41.3% vs. 22.0%, p = 0.016). Need mechanical ventilation, p-SOFA, acute liver failure, higher fluid overload at CRRT initiation, hypoalbuminemia, and high inotropic support were associated with PICU mortality in cancer-related sepsis patients. Moreover, levels of IL-6, total bilirubin, creatinine, blood urea nitrogen, and international normalized ratio were significantly higher in non-survivors than survivors. In multivariate logistic regression analysis, pediatric sequential organ failure assessment (p-SOFA) score (OR:1.805 [95%CI: 1.047-3.113]) and serum albumin level (OR: 0.758 [95%CI: 0.581 -0.988]) were death risk factors in cancer-related sepsis receiving CRRT, and the AUC of combined index of p-SOFA and albumin was 0.852 (95% CI: 0.730-0.974). CONCLUSION: The overall PICU mortality is high in cancer-related sepsis necessitating CRRT. Higher p-SOFA and lower albumin were independent risk factors for PICU mortality.

Isoflurane Preconditioning Alleviates Hypoxia/Reoxygenation-Induced Cardiomyocyte Injury by Inhibiting miR-195-3p Expression.

To investigate the role of microRNA-195-3p (miR-195-3p) in hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury. AC16 human cardiomyocyte cells were cultured and pretreated with different concentrations of isoflurane (ISO) (1%, 2%, and 3%), followed by 6 h each of hypoxia and reoxygenation to construct H/R cell models. The optimum ISO concentration was assessed based on the cell viability. miR-195-3p expression was regulated by in vitro cell transfection. Cell viability was determined by MTT assay, and apoptosis was evaluated by flow cytometry. The levels of myocardial injury and inflammation were determined by enzyme-linked immunosorbent assay. Compared with the control group, the cell viability of the H/R group had significantly decreased and that of ISO pretreatment had increased in a dose-dependent manner. Therefore, we selected a 2% ISO concentration for pretreatment. MiR-195-3p expression had significantly increased in the H/R group and decreased after 2% ISO pretreatment. Additionally, the number of apoptotic cells and the levels of lactate dehydrogenase, creatine kinase-myoglobin binding, cardiac troponin I, interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α had increased significantly. ISO preconditioning inhibited H/R-induced AC16 cell damage, whereas miR-195-3p overexpression reversed the protective effects of ISO on cardiomyocytes. The expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was reduced in the H/R-induced AC16 cells, and PTEN is a downstream target gene of miR-195-3p. Preconditioning with 2% ISO plays a protective role in H/R-induced AC16 cell damage by inhibiting miR-195-3p expression.

The Role of mRNA Alternative Splicing in Macrophages Infected with Mycobacterium tuberculosis: A Field Needing to Be Discovered.

Mycobacterium tuberculosis (Mtb) is one of the major causes of human death. In its battle with humans, Mtb has fully adapted to its host and developed ways to evade the immune system. At the same time, the human immune system has developed ways to respond to Mtb. The immune system responds to viral and bacterial infections through a variety of mechanisms, one of which is alternative splicing. In this study, we summarized the overall changes in alternative splicing of the transcriptome after macrophages were infected with Mtb. We found that after infection with Mtb, cells undergo changes, including (1) directly reducing the expression of splicing factors, which affects the regulation of gene expression, (2) altering the original function of proteins through splicing, which can involve gene truncation or changes in protein domains, and (3) expressing unique isoforms that may contribute to the identification and development of tuberculosis biomarkers. Moreover, alternative splicing regulation of immune-related genes, such as IL-4, IL-7, IL-7R, and IL-12R, may be an important factor affecting the activation or dormancy state of Mtb. These will help to fully understand the immune response to Mtb infection, which is crucial for the development of tuberculosis biomarkers and new drug targets.

Association between brominated flame retardants and risk of endocrine-related cancer: A systematic review and meta-analysis.

BACKGROUND: The incidence of endocrine-related cancer, which includes tumors in major endocrine glands such as the breast, thyroid, pituitary, and prostate, has been increasing year by year. Various studies have indicated that brominated flame retardants (BFRs) are neurotoxic, endocrine-toxic, reproductive-toxic, and even carcinogenic. However, the epidemiological relationship between BFR exposure and endocrine-related cancer risk remains unclear. METHODS: We searched the PubMed, Google Scholar, and Web of Science databases for articles evaluating the association between BFR exposure and endocrine-related cancer risk. The odds ratio (OR) and its corresponding 95% confidence interval (95% CI) were used to assess the association. Statistical heterogeneity among studies was assessed with the Q-test and I2 statistics. Begg's test was performed to evaluate the publication bias. RESULTS: We collected 15 studies, including 6 nested case-control and 9 case-control studies, with 3468 cases and 4187 controls. These studies assessed the risk of breast cancer, thyroid cancer, and endocrine-related cancers in relation to BFR levels. Our findings indicate a significant association between BFR exposure in adipose tissue and an increased risk of breast cancer. However, this association was not observed for thyroid cancer. Generally, BFR exposure appears to elevate the risk of endocrine-related cancers, with a notable increase in risk linked to higher levels of BDE-28, a specific polybrominated diphenyl ether congener. CONCLUSIONS: In conclusion, although this meta-analysis has several limitations, our results suggest that BFR exposure is a significant risk factor for breast cancer, and low-brominated BDE-28 exposure could significantly increase the risk of endocrine-related cancers. Further research is essential to clarify the potential causal relationships between BFRs and endocrine-related cancers, and their carcinogenic mechanisms.

Redox-dependent Cd2+ inhibition of BK-type Ca2+-activated K+ channels.

Large-conductance Ca2+-activated K+ channels (BK channels) are formed by Slo1 subunits as a homotetramer. Besides Ca2+, other divalent cations, such as Cd2+, also activate BK channels when applied intracellularly by shifting the conductance-voltage relation to more negative voltages. However, we found that if the inside-out patch containing BK channels was treated with solution containing reducing agents such as dithiothreitol (DTT), then subsequent Cd2+ application completely inhibited BK currents. The DTT-dependent Cd2+ inhibition could be reversed by treating the patch with solutions containing H2O2, suggesting that a redox reaction regulates the Cd2+ inhibition of BK channels. Similar DTT-dependent Cd2+ inhibition was also observed in a mutant BK channel, Core-MT, in which the cytosolic domain of the channel is deleted, and in the proton-activated Slo3 channels but not observed in the voltage-gated Shaker K+ channels. A possible mechanism for the DTT-dependent Cd2+ inhibition is that DTT treatment breaks one or more disulfide bonds between cysteine pairs in the BK channel protein and the freed thiol groups coordinate with Cd2+ to form an ion bridge that blocks the channel or locks the channel at the closed state. However, surprisingly, none of the mutations of all cysteine residues in Slo1 affect the DTT-dependent Cd2+ inhibition. These results are puzzling, with an apparent contradiction: on one hand, a redox reaction seems to regulate Cd2+ inhibition of the channel, but on the other hand, no cysteine residue in the Slo1 subunit seems to be involved in such inhibition.

Association between NTCP hepatic expression and inflammation/fibrosis as well as gender-specific differences in chronic HBV-infected patients.

To investigate the relationship between the expression of hepatitis B virus (HBV) functional receptor sodium taurocholate cotransporting polypeptide (NTCP) with disease progression and gender-specific differences in chronic HBV-infected patients. Liver samples were collected from chronic HBV-infected patients who underwent percutaneous liver biopsy or liver surgery. HBV DNA levels and the mRNA and protein expression levels of NTCP in liver tissues were determined. The relationship between NTCP expression and HBV DNA levels, inflammatory activity, fibrosis, and gender-specific differences were analyzed. A total of 94 chronic HBV-infected patients were included. Compared with patients with a METAVIR score of A0-1 or F0-1, patients with score of A2 or F2/F3 had a relatively higher level of NTCP expression. NTCP levels were positively correlated with HBV DNA levels. The inflammatory activity scores and fibrosis scores of women <50 years were significantly lower than those of women ≥50 years and age-matched males. In patients with score A0-2 or F0-3, women <50 years have lower NTCP expression level compared to women ≥50 years and age-matched males. NTCP can promote the disease progression by affecting the viral load of HBV. The NTCP expression difference may be why male and postmenopausal women are more prone to disease progression than reproductive women.

Exposure to disinfection by-products and risk of cancer: A systematic review and dose-response meta-analysis.

Disinfection by-products (DBPs), including trihalomethanes (THMs) and haloacetic acids (HAAs), have attracted attention due to their carcinogenic properties, leading to varying conclusions. This meta-analysis aimed to evaluate the dose-response relationship and the dose-dependent effect of DBPs on cancer risk. We performed a selective search in PubMed, Web of Science, and Embase databases for articles published up to September 15th, 2023. Our meta-analysis eventually included 25 articles, encompassing 8 cohort studies with 6038,525 participants and 10,668 cases, and 17 case-control studies with 10,847 cases and 20,702 controls. We observed a positive correlation between increased cancer risk and higher concentrations of total trihalomethanes (TTHM) in water, longer exposure durations, and higher cumulative TTHM intake. These associations showed a linear trend, with relative risks (RRs) and 95 % confidence intervals (CIs) being 1.02 (1.01-1.03), 1.04 (1.02-1.06), and 1.02 (1.00-1.03), respectively. Gender-specific analyses revealed slightly U-shaped relationships in both males and females, with males exhibiting higher risks. The threshold dose for TTHM in relation to cancer risk was determined to be 55 µg/L for females and 40 µg/L for males. A linear association was also identified between bladder cancer risk and TTHM exposure, with an RR and 95 % CI of 1.08 (1.05-1.11). Positive linear associations were observed between cancer risk and exposure to chloroform, bromodichloromethane (BDCM), and HAA5, with RRs and 95 % CIs of 1.02 (1.01-1.03), 1.33 (1.18-1.50), and 1.07 (1.03-1.12), respectively. Positive dose-dependent effects were noted for brominated THMs above 35 µg/L and chloroform above 75 µg/L. While heterogeneity was observed in the studies for quantitative synthesis, no publication bias was detected. Exposure to TTHM, chloroform, BDCM, or HAA5 may contribute to carcinogenesis, and the risk of cancer appears to be dose-dependent on DBP exposure levels. A cumulative effect is suggested by the positive correlation between TTHM exposure and cancer risk. Bladder cancer and endocrine-related cancers show dose-dependent and positive associations with TTHM exposure. Males may be more susceptible to TTHM compared to females.

SORC: an integrated spatial omics resource in cancer.

The interactions between tumor cells and the microenvironment play pivotal roles in the initiation, progression and metastasis of cancer. The advent of spatial transcriptomics data offers an opportunity to unravel the intricate dynamics of cellular states and cell-cell interactions in cancer. Herein, we have developed an integrated spatial omics resource in cancer (SORC, http://bio-bigdata.hrbmu.edu.cn/SORC), which interactively visualizes and analyzes the spatial transcriptomics data in cancer. We manually curated currently available spatial transcriptomics datasets for 17 types of cancer, comprising 722 899 spots across 269 slices. Furthermore, we matched reference single-cell RNA sequencing data in the majority of spatial transcriptomics datasets, involving 334 379 cells and 46 distinct cell types. SORC offers five major analytical modules that address the primary requirements of spatial transcriptomics analysis, including slice annotation, identification of spatially variable genes, co-occurrence of immune cells and tumor cells, functional analysis and cell-cell communications. All these spatial transcriptomics data and in-depth analyses have been integrated into easy-to-browse and explore pages, visualized through intuitive tables and various image formats. In summary, SORC serves as a valuable resource for providing an unprecedented spatially resolved cellular map of cancer and identifying specific genes and functional pathways to enhance our understanding of the tumor microenvironment.

Coumarins from Jinhua Finger Citron: Separation by Liquid-Liquid Chromatography and Potential Antitumor Activity.

In this paper, liquid-liquid chromatography was introduced for the first time for the separation of fingered citron (Citrus medica L. var. sarcodactylis Swingle). The fingered citron cultivated in Jinhua is of significant industrial and medicinal value, with several major coumarin compounds detected in its extract. Therefore, further separation for higher purity was of necessity. A preparative liquid-liquid chromatographic method was developed by combining two elution modes (isocratic and step-gradient) with selection according to different polarities of the target sample. Five coumarin derivatives-5,7-dimethoxycoumarin (52.6 mg, 99.6%), phellopterin (4.9 mg, 97.1%), 5-prenyloxy-7-methoxycoumarin (6.7 mg, 98.7%), 6-hydroxy-7-methoxycoumarin (7.1 mg, 82.2%), and byakangelicol (10.5 mg, 90.1%)-with similar structures and properties were isolated on a large scale from 100 mg of petroleum ether (PE) extract and 100 mg of ethyl acetate (EA) extract in Jinhua fingered citron. The productivity was much improved. The anti-growth activity of the isolated coumarins was evaluated against three cancer cell lines (HeLa, A549, and MCF7) with an MTT assay. The coumarins demonstrated potential anti-tumor activity on the HeLa cell line, with 5,7-dimethoxycoumarin in particular exhibiting the best anti-growth activity (IC50 = 10.57 ± 0.24 µM) by inhibiting proliferation. It inhibited colony formation and reduced the size of the tumor sphere in a concentration-dependent manner. The main mechanism was confirmed as inducing apoptosis. This work was informative for further studies aimed at exploring new natural-product-based antitumor agents.

Fluid Supplementation Through Weakened Zonules via Side-Port Incision to Maintain Intraocular Pressure in High Myopic Eyes.

INTRODUCTION: During phacoemulsification, the infusion pressure can cause the liquefied vitreous fluid to escape through the ciliary fiber interspace in highly myopic eyes, leading to reduced vitreous cavity pressure similar to vitrectomized eyes. This study assessed the probability of low intraocular pressure (IOP) in high myopic eyes with different axial length (AL) group undergoing cataract surgery, as well as the impact of balanced salt solution (BSS) supplementation and the optimal IOP value for such supplementation. METHODS: The control group consisted of cataract eyes with normal AL (group 1: 22 mm ≤ AL < 24.5 mm), while cataract eyes with high axial myopia were categorized into three groups (group 2: 26 mm ≤ AL < 28 mm, group 3: 28 mm ≤ AL < 30 mm, group 4: AL ≥ 30 mm). IOP was measured using the iCare pro tonometer intraoperatively. BSS supplementation was performed to raise IOP in cases of low IOP, before intraocular lens (IOL) implantation and before the end of surgery. The probability of low IOP was calculated, and the IOP before and after supplementation were compared. RESULTS: Ninety-five eyes were included. The total probability of low IOP in groups 2, 3, and 4 was 56.52, 62.50, and 70.83%, respectively, significantly higher than that in group 1 (16.67%). Similarly, the probability of low IOP before IOL implantation was significantly higher in groups 2, 3, 4 (43.48, 41.67, and 62.50%) compared to group 1 (4.17%, P < 0.05). The IOP before and after the first BSS supplementation in three high myopia groups were statistically significant (P < 0.05), increasing from 12.10 mmHg (range, 6.0-24.9 mmHg) to 16.60 mmHg (range, 10.2-34.4 mmHg). After the second BSS supplementation before the end of surgery, the IOP of high myopia groups increased from 12.60 mmHg (range, 7.0-25.3 mmHg) to 14.60 mmHg (range, 9.8-25.3 mmHg). CONCLUSIONS: The condition of highly myopic eyes seems more likely to develop low IOP during cataract surgery. There is an observed correlation: as AL increases, the total probability of low IOP rises. In patients with IOP < 9.5 mmHg intraoperatively, fluid supplementation via a side-port incision can effectively raise IOP to about 16 mmHg before IOL implantation and about 14 mmHg after incision sealing, facilitating smoother IOL implantation and reducing the risk of postoperative low IOP. TRIAL REGISTRATION: NCT, NCT05201677. Registered 23 November 2021-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT05201677 .

ATF4 knockdown in macrophage impairs glycolysis and mediates immune tolerance by targeting HK2 and HIF-1α ubiquitination in sepsis.

Strengthened glycolysis is crucial for the macrophage pro-inflammatory response during sepsis. Activating transcription factor 4 (ATF4) plays an important role in regulating glucose and lipid metabolic homeostasis in hepatocytes and adipocytes. However, its immunometabolic role in macrophage during sepsis remains largely unknown. In the present study, we found that the expression of ATF4 in peripheral blood mononuclear cells (PBMCs) was increased and associated with glucose metabolism in septic patients. Atf4 knockdown specifically decreased LPS-induced spleen macrophages and serum pro-inflammatory cytokines levels in mice. Moreover, Atf4 knockdown partially blocked LPS-induced pro-inflammatory cytokines, lactate accumulation and glycolytic capacity in RAW264.7. Mechanically, ATF4 binds to the promoter region of hexokinase II (HK2), and interacts with hypoxia inducible factor-1α (HIF-1α) and stabilizes HIF-1α through ubiquitination modification in response to LPS. Furthermore, ATF4-HIF-1α-HK2-glycolysis axis launches pro-inflammatory response in macrophage depending on the activation of mammalian target of rapamycin (mTOR). Importantly, Atf4 overexpression improves the decreased level of pro-inflammatory cytokines and lactate secretion and HK2 expression in LPS-induced tolerant macrophages. In conclusion, we propose a novel function of ATF4 as a crucial glycolytic activator contributing to pro-inflammatory response and improving immune tolerant in macrophage involved in sepsis. So, ATF4 could be a potential new target for immunotherapy of sepsis.

A global database for modeling tumor-immune cell communication.

Communications between tumor cells and surrounding immune cells help shape the tumor immunity continuum. Recent breakthroughs in high-throughput technologies as well as computational algorithms had reported many important tumor-immune cell (TIC) communications, which were scattered in thousands of published studies and impeded systematical characterization of the TIC communications across cancer. Here, a comprehensive database, TICCom, was developed to model TIC communications, containing 739 experimentally-validated or manually-curated interactions collected from more than 3,000 literatures as well as 4,537,709 predicted interactions inferred via six computational algorithms by reanalyzing 32 scRNA-seq datasets and bulk RNA-seq data across 25 cancer types. The communications between tumor cells and 14 types of immune cells were characterized, and the involved ligand-receptor interactions were further integrated. 14190 human and 3650 mouse integrated ligand-receptor interactions with supplemented corresponding function information were also stored in the TICCom database. Our database would serve as a valuable resource for investigating TIC communications.

Effect of metastasectomy on the outcome of patients with ovarian metastasis of colorectal cancer: A systematic review and meta-analysis.

PURPOSE: Patients with ovarian metastasis of colorectal cancer (CROM) usually have poor prognosis. Metastasectomy is controversial in patients with CROM. This study aims to evaluate the prognostic value of ovarian metastasectomy and other factors in CROM patients. METHODS: We searched literature up to November 1, 2021 in MEDLINE (PubMed), Embase, Cochrane Library, and Clinicaltrials.gov. Retrospective studies were assessed if survival outcome of CROM patients was reported. Results were pooled in a random-effects model and reported as hazard ratios (HRs) with 95% confidence intervals (CI). Sensitivity was analyzed. RESULTS: Among 2497 studies screened, 15 studies with 997 patients, published between 2000 and 2021, were included. Longer overall survival (OS) was correlated with ovarian metastasectomy (pooled HR = 0.44, 95% CI: 0.34-0.58, P < 0.05) and R0 resection (pooled HR = 0.26, 95% CI: 0.16-0.41, P < 0.05). Longer disease-specific survival (DSS) was associated with systematic chemotherapy (pooled HR = 0.26, 95% CI: 0.15-0.45, P < 0.0001). Shorter OS was associated with extraovarian metastases (pooled HR = 3.00, 95% CI 1.68-5.36, P < 0.05) and bilateral OM (pooled HR = 1.66, 95% CI: 1.09-2.51, P < 0.05). No significant difference in OS was observed among patients with systematic chemotherapy (pooled HR = 0.68, 95% CI: 0.35-1.31, P > 0.05). CONCLUSION: Metastasectomy achieving R0 resection can significantly prolong OS and DSS of CROM patients as a reasonable treatment modality. Primary tumor resection and systematic chemotherapy can improve patients' outcomes. REGISTRATION NUMBER: CRD42022299185 (http://www.crd.york.ac.uk/PROSPERO).

Identification of a prognostic signature and ENTR1 as a prognostic biomarker for colorectal mucinous adenocarcinoma.

Background: Mucinous adenocarcinoma (MAC) is a unique clinicopathological colorectal cancer (CRC) type that has been recognized as a separate entity from non-mucinous adenocarcinoma (NMAC), with distinct clinical, pathologic, and molecular characteristics. We aimed to construct prognostic signatures and identifying candidate biomarkers for patients with MAC. Methods: Differential expression analysis, weighted correlation network analysis (WGCNA), and least absolute shrinkage and selection operator (LASSO)-Cox regression model were used to identify hub genes and construct a prognostic signature based on RNA sequencing data from TCGA datasets. The Kaplan-Meier survival curve, gene set enrichment analysis (GSEA), cell stemness, and immune infiltration were analyzed. Biomarker expression in MAC and corresponding normal tissues from patients operated in 2020 was validated using immunohistochemistry. Results: We constructed a prognostic signature based on ten hub genes. Patients in the high-risk group had significantly worse overall survival (OS) than patients in the low-risk group (p < 0.0001). We also found that ENTR1 was closely associated with OS (p = 0.016). ENTR1 expression was significantly positively correlated with cell stemness of MAC (p < 0.0001) and CD8+ T cell infiltration (p = 0.01), whereas it was negatively associated with stromal scores (p = 0.03). Finally, the higher expression of ENTR1 in MAC tissues than in normal tissues was validated. Conclusion: We established the first MAC prognostic signature, and determined that ENTR1 could serve as a prognostic marker for MAC.

Radioimmunotherapy in colorectal cancer treatment: present and future.

Colorectal cancer (CRC) is a deadly form of cancer worldwide. Patients with locally advanced rectal cancer and metastatic CRC have a poor long-term prognosis, and rational and effective treatment remains a major challenge. Common treatments include multi-modal combinations of surgery, radiotherapy, and chemotherapy; however, recurrence and metastasis rates remain high. The combination of radiotherapy and immunotherapy (radioimmunotherapy [RIT]) may offer new solutions to this problem, but its prospects remain uncertain. This review aimed to summarize the current applications of radiotherapy and immunotherapy, elaborate on the underlying mechanisms, and systematically review the preliminary results of RIT-related clinical trials for CRC. Studies have identified several key predictors of RIT efficacy. Summarily, rational RIT regimens can improve the outcomes of some patients with CRC, but current study designs have limitations. Further studies on RIT should focus on including larger sample sizes and optimizing the combination therapy regimen based on underlying influencing factors.

A selective fluorescent probe for hydrogen sulfide from a series of flavone derivatives and intracellular imaging.

In this work, through the orthogonal design of two fluorophores and two recognition groups, a series of fluorescent probes were developed from the flavone derivatives for hydrogen sulfide (H2S). The probe FlaN-DN stood out from the primarily screening on the selectivity and response intensities. It could respond to H2S with both the chromogenic and fluorescent signals. Among the recent reported probes for the H2S detection, FlaN-DN indicated the most highlighted advantages including the rapid response (within 200 s) and the high response multiplication (over 100 folds). FlaN-DN was sensitive to the pH condition, thus could be applied to distinguish the cancer micro-environment. Moreover, FlaN-DN suggested practical capabilities including a wide linear range (0-400 µM), a relatively high sensitivity (limit of detection 0.13 µM), and high selectivity towards H2S. As a low cytotoxic probe, FlaN-DN achieved the imaging in living HeLa cells. FlaN-DN could detect the endogenous generation H2S and visualize the dose-dependent responses to the exogenous H2S level. This work provided a typical case of natural-sourced derivatives as functional implements, which might inspire the future investigations.