In Situ Electropolymerizing Toward EP-CoP/Cu Tandem Catalyst for Enhanced Electrochemical CO2-to-Ethylene Conversion.

Electrochemical CO2 reduction has garnered significant interest in the conversion of sustainable energy to valuable fuels and chemicals. Cu-based bimetallic catalysts play a crucial role in enhancing *CO concentration on Cu sites for efficient C─C coupling reactions, particularly for C2 product generation. To enhance Cu's electronic structure and direct its selectivity toward C2 products, a novel strategy is proposed involving the in situ electropolymerization of a nano-thickness cobalt porphyrin polymeric network (EP-CoP) onto a copper electrode, resulting in the creation of a highly effective EP-CoP/Cu tandem catalyst. The even distribution of EP-CoP facilitates the initial reduction of CO2 to *CO intermediates, which then transition to Cu sites for efficient C─C coupling. DFT calculations confirm that the *CO enrichment from Co sites boosts *CO coverage on Cu sites, promoting C─C coupling for C2+ product formation. The EP-CoP/Cu gas diffusion electrode achieves an impressive current density of 726 mA cm-2 at -0.9 V versus reversible hydrogen electrode (RHE), with a 76.8% Faraday efficiency for total C2+ conversion and 43% for ethylene, demonstrating exceptional long-term stability in flow cells. These findings mark a significant step forward in developing a tandem catalyst system for the effective electrochemical production of ethylene.

Proanthocyanidins inhibited colorectal cancer stem cell characteristics through Wnt/ß-catenin signaling.

BACKGROUND: Cancer stem cells (CSCs) play a key role in tumor cell growth, drug resistance, recurrence, and metastasis. Proanthocyanidins (PC) is widely existed in plants and endowed with powerful antioxidant and anti-aging effects. Interestingly, recent studies have found that PC exhibits the inhibitory effect on tumor growth. However, the role of PC in CSCs of colorectal cancer (CRC) and molecular mechanism remain unclear. METHODS: CCK-8, colony, and tumorsphere formation assay were used to evaluate cancer cell viability and stemness, respectively. Western blotting was used to detect the protein expression. Tumor xenograft experiments were employed to examine the tumorigenicity of CRC cells in nude mice. RESULTS: PC decreased the proliferation of CRC cells (HT29 and HCT-116), and improved the sensitivity of CRC cells to oxaliplatin (L-OHP), as well as inhibited tumor growth in nude mice. Further studies showed that PC also down-regulated CSCs surface molecular and stemness transcriptional factors, while suppressed the formations of tumorspheres and cell colony in CRC. In addition, PC-impaired proteins expressions of p-GSK3ß, ß-catenin and DVL1-3. LiCl, an activator of the Wnt/ß-catenin signaling, rescued PC-induced downregulation of CSCs markers, and reduction of tumorspheres and cell colony formation abilities in CRC cells. Furthermore, the effects of PC on inhibiting cell proliferation and enhancing L-OHP sensitivity were impaired by LiCl. CONCLUSIONS: PC exerted an inhibitory effect on CSCs via Wnt/ß-catenin in CRC, and may be a potential new class of natural drug for CRC treatment.

Combining hyperspectral imaging techniques with deep learning to aid in early pathological diagnosis of melanoma.

BACKGROUND: Cutaneous melanoma, an exceedingly aggressive form of skin cancer, holds the top rank in both malignancy and mortality among skin cancers. In early stages, distinguishing malignant melanomas from benign pigmented nevi pathologically becomes a significant challenge due to their indistinguishable traits. Traditional skin histological examination techniques, largely reliant on light microscopic imagery, offer constrained information and yield low-contrast results, underscoring the necessity for swift and effective early diagnostic methodologies. As a non-contact, non-ionizing, and label-free imaging tool, hyperspectral imaging offers potential in assisting pathologists with identification procedures sans contrast agents. METHODS: This investigation leverages hyperspectral cameras to ascertain the optical properties and to capture the spectral features of malignant melanoma and pigmented nevus tissues, intending to facilitate early pathological diagnostic applications. We further enhance the diagnostic process by integrating transfer learning with deep convolutional networks to classify melanomas and pigmented nevi in hyperspectral pathology images. The study encompasses pathological sections from 50 melanoma and 50 pigmented nevus patients. To accurately represent the spectral variances between different tissues, we employed reflectance calibration, highlighting that the most distinctive spectral differences emerged within the 500-675 nm band range. RESULTS: The classification accuracy of pigmented tumors and pigmented nevi was 89% for one-dimensional sample data and 98% for two-dimensional sample data. CONCLUSIONS: Our findings have the potential to expedite pathological diagnoses, enhance diagnostic precision, and offer novel research perspectives in differentiating melanoma and nevus.

Dihydroartemisinin inhibited stem cell-like properties and enhanced oxaliplatin sensitivity of colorectal cancer via AKT/mTOR signaling.

Colorectal cancer (CRC) is a common tumor with high morbidity and mortality. The use of oxaliplatin (L-OHP) as a first-line treatment for CRC is limited due to chemoresistance. Growing evidence have revealed that the existence of cancer stem-like cells (CSLCs) is one of the important reasons for drug resistance and recurrence of cancers. Dihydroartemisinin (DHA), a derivative of artemisinin, has showed anticancer effects on a variety of malignancies, in addition to its antimalarial effects. However, the effect and mechanism of DHA on CSLCs and chemosensitivity in CRC cells remains unclear. In this study, we found that DHA inhibited cell viability in HCT116 and SW620 cells. Moreover, DHA decreased cell clonogenicity, and improved L-OHP sensitivity. Furthermore, DHA treatment attenuated tumor sphere formation, and the expressions of stem cell surface marker (CD133 and CD44) and stemness-associated transcription factor (Nanog, c-Myc, and OCT4). Mechanistically, the present findings showed that DHA inhibited of AKT/mTOR signaling pathway. The activation of AKT/mTOR signaling reversed DHA-decreased cell viability, clonogenicity, L-OHP resistance, tumor sphere, and expressions of stemness-associated protein in CRC. The inhibitory effect of DHA on tumorigenicity of CRC cells has also been demonstrated in BALB/c nude mice. In conclusion, this study revealed that DHA inhibited CSLCs properties in CRC via AKT/mTOR signaling, suggesting that DHA may be used as a potential therapeutic agent for CRC.

Circ_0084188 Regulates the progression of colorectal cancer through the miR-769-5p/KIF20A axis.

BACKGROUND: Colorectal cancer (CRC) is one of the major gastrointestinal malignancies threatening human health. More and more studies indicate that circular RNAs (circRNAs) are important regulatory factors of CRC, but the mechanism is still indistinct. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect the expression of circ_0084188, microRNA-769-5p (miR-769-5p), and kinesin family member 20A (KIF20A) in CRC tissues. Kaplan-Meier curve was used to analyze the relationship between circ_0084188 expression and the survival rate of CRC patients. Cell proliferation, viability, apoptosis, migration, and invasion were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, wound-healing, and transwell assays, respectively. The relationship between miR-769-5p and circ_0084188 or KIF20A was detected by a dual-luciferase reporter and RNA pull-down. The effect of circ_0084188 on tumor growth was verified by xenograft studies in vivo. RESULTS: Circ_0084188 and KIF20A were upregulated and miR-769-5p was downregulated in CRC. Circ_0084188 knockdown repressed the proliferation, migration, and invasion of CRC cells, as well as enhanced apoptosis in vitro. Mechanistically, circ_0084188 targeted miR-769-5p, and the reduction of miR-769-5p reversed the effects of circ_0084188 knockdown on cell functional behaviors. KLF20A was a direct miR-769-5p target, and circ_0084188 acted as a sponge for miR-769-5p to regulate the KIF20A level. Moreover, miR-769-5p regulated the functional behaviors of CRC cells by targeting KIF20A. In addition, circ_0084188 knockdown confined the growth of xenograft tumors in vivo. CONCLUSION: Circ_0084188 upregulated the expression of KIF20A to promote the tumorigenesis of CRC through miR-769-5p, providing a new therapeutic target for CRC.

N6-methyladenosine-mediated LDHA induction potentiates chemoresistance of colorectal cancer cells through metabolic reprogramming.

Background: Chemoresistance to 5-fluorouracil (5-FU) is a major barrier to influence the treatment efficiency of colorectal cancer (CRC) patients, while the precise molecular mechanisms underlying 5-FU resistance remain to be fully elucidated. Methods: The metabolic profiles including ATP generation, glucose consumption, lactate generation, and oxygen consumption rate (OCR) in 5-FU resistant CRC cells were compared with those in their parental cells. Subsequently, a series of in vitro and in vivo experiments were carried out to investigate the mechanisms responsible for metabolic reprogramming of 5-FU resistant CRC cells. Results: We found that 5-FU resistant CRC cells showed increased levels of ATP generation, glucose consumption, lactate generation, and OCR as compared with those in their parental cells. Further, increased levels of mRNA N6-methyladenosine (m6A) and methyltransferase-like 3 (METTL3) were observed in 5-FU resistant CRC cells. Inhibition or knockdown of METTL3 can suppress glycolysis and restore chemosensitivity of 5-FU resistant CRC cells. Mechanistically, METTL3 enhances the expression of LDHA, which catalyzes the conversion of pyruvate to lactate, to trigger glycolysis and 5-FU resistance. METTL3 can increase the transcription of LDHA via stabilizing mRNA of hypoxia-inducible factor (HIF-1α), further, METTL3 also triggers the translation of LDHA mRNA via methylation of its CDS region and recruitment of YTH domain-containing family protein 1 (YTHDF1). Targeted inhibition of METTL3/LDHA axis can significantly increase the in vitro and in vivo 5-FU sensitivity of CRC cells. Conclusion: Our study indicates that METTL3/LDHA axis-induced glucose metabolism is a potential therapy target to overcome 5-FU resistance in CRC cells.

Ring finger protein 128 promotes, rather than inhibits, colorectal cancer progression by regulating the Hippo signaling pathway.

Background: Colorectal cancer is a common malignancy of the gastrointestinal tract, and its incidence and mortality rates have increased in recent years. RNF128 is an E3 ubiquitin ligase that plays an important role as a suppressor gene or oncogene in various cancers, but its mechanism in colorectal cancer is not yet clear. The aim of this study was to investigate the role and mechanism of RNF128 in colorectal cancer. Methods: The expression of RNF128 in colorectal cancer tissues was assessed by immunohistochemistry and western blotting. The proliferation ability of colorectal cancer cells was measured by colony formation assay and CCK-8 assay, the migration and invasion ability of colorectal cancer cells was measured by wound healing assay and transwell assay, and the protein expression levels of the Hippo signaling pathway and its target gene were examined by western blotting. Immunoprecipitation was used to assess the interaction of RNF128 with MST. In vivo, a xenograft tumor model was used to detect the effect of RNF128 on tumor growth. Results: At the tissue level, the expression level of RNF128 was significantly higher in colorectal cancer tissues than in adjacent normal tissues. In LoVo cells and HCT116 cells, the proliferation, migration and invasion abilities were significantly reduced with RNF128 knockdown. At the protein level, knockdown of RNF128 resulted in significant activation of the Hippo signaling pathway. In vivo experiments, the volume and weight of xenograft tumors in nude mice were significantly decreased compared with those in the normal control group with RNF128 knockdown. Conclusion: RNF128 promotes the malignant behaviors of colorectal cancer cells by inhibiting the Hippo signaling pathway, which may provide a new target for colorectal cancer prevention and treatment.

Identification of circRNA circ-CSPP1 as a potent driver of colorectal cancer by directly targeting the miR-431/LASP1 axis.

Colorectal cancer (CRC) is the third most common malignancy worldwide. Circular RNAs (circRNAs) have been implicated in cancer biology. The purpose of the current work is to investigate the precise parts of circRNA centrosome and spindle pole-associated protein 1 (circ-CSPP1) in the progression of CRC. Our data showed that circ-CSPP1 was significantly overexpressed in CRC tissues and cells. The knockdown of circ-CSPP1 attenuated cell proliferation, migration, invasion and promoted apoptosis in vitro and weakened tumor growth in vivo. circ-CSPP1 directly targeted miR-431, and circ-CSPP1 knockdown modulated CRC cell progression in vitro via upregulating miR-431. Moreover, LIM and SH3 protein 1 (LASP1) was a functional target of miR-431 in modulating CRC cell malignant progression. Furthermore, circ-CSPP1 in CRC cells functioned as a posttranscriptional regulator on LASP1 expression by targeting miR-431. Our present study identified the oncogenic role of circ-CSPP1 in CRC partially by the modulation of the miR-431/LASP1 axis, providing evidence for circ-CSPP1 as a promising biomarker for CRC management.

Meta-analysis on current status, efficacy, and safety of laparoscopic and robotic ventral mesh rectopexy for rectal prolapse treatment: can robotic surgery become the gold standard?

PURPOSE: Robotic-assisted surgery and robotic-assisted ventral mesh rectopexy are gaining attention in the treatment of rectal prolapse and increased positive findings are proposed. The objective of this meta-analysis was to investigate whether robotic-assisted ventral mesh rectopexy is comparable with the conventional laparoscopic approach surgery. METHODS: Five major databases (PubMed, Sciencedirect, Web of Science, Embase, and Cochrane Library) were searched for eligible studies. Observational studies of the effect and safety of robotic-assisted and laparoscopic approaches on ventral mesh rectopexy were included. Odd ratios (OR) and weight mean difference (WMD) were used for dichotomous data and continuous data analysis. Clinical outcomes, functional outcomes, and cost-effectiveness data were extracted for meta-analysis. RESULTS: Compared to the laparoscopic approach, a significant shorter length of hospital stay (LOS), lesser intraoperative blood loss, and lower post-operative complication rate of RVMR group were observed. However, operation time of RVMR was significant increased. The expense of RVMR was higher than LVMR; mean Wexner scores and fecal incontinence were lower in RVMR group while there were no statistical differences. CONCLUSION: The result of the current analysis revealed that the robotic-assisted ventral mesh rectopexy is effective and feasible in the treatment of rectal prolapse. However, long-term follow-up and results are needed for the promotion of this approach. There is a long way for robotic-assisted surgery to become a gold standard in rectal surgery.

Wnt/catenin ß1/microRNA 183 predicts recurrence and prognosis of patients with colorectal cancer.

The present study assessed the association between the Wnt/catenin ß1 (CTNNB1)/microRNA (miR)183 signaling pathway and the recurrence and prognosis of colorectal cancer. The expression of Wnt, CTNNB1 and miR183 in primary colorectal cancer tissue was increased compared with that in the paracarcinoma tissue. Disease-free survival and overall survival were decreased in patients with colorectal cancer and increased miR183 expression compared with those in patients with colorectal cancer and decreased miR183 expression. The human colorectal cancer cell line HCT-116 was treated with 5 µM inhibitor of Wnt response (IWR-2) for 24 h to inhibit Wnt protein expression. Downregulating Wnt and CTNNB1 expression inhibited the viability of, and induced cell death and caspase 3 protein expression in, HCT-116 cells. The expression of BCL2 associated X protein and miR183 was increased, and cyclin D1 protein expression was suppressed, by the downregulation of Wnt and CTNNB1 expression in HCT-116 cells. Collectively, the results of the present study suggested that the Wnt/CTNNB1/miR183 signaling pathway may represent a promising biomarker for the recurrence and prognosis of colorectal cancer.

[Long-term outcome of tension-free hernioplasty for inguinal hernia complicated with liver cirrhosis and ascites].

OBJECTIVE: To review tension-free repairing for the patients with inguinal hernia complicated with cirrhosis and ascites. METHODS: Tension-free herniorrhaphy was performed in 16 cases with inguinal hernia complicated with cirrhosis and ascites from November 1999 to November 2003. The laboratory data before and after the operation were compared and analyzed in this group. RESULTS: Of the patients, 13 cases were male and 3 were female, the mean age was (64 ± 12) years (range, 37 - 85 years). The liver function was classified as A degree in 4 case, B degree in 10 cases and C degree in 2 patients by using Child score. The operation was successfully carried out in all patients without complications and post-operative hepatoencephalopathy. There was no significant change in the plasma total protein, bilirubin, prothrombin activity and international normalized ratio (INR) after the operation. And the levels of albumin, globulin and white blood cell count changed remarkably after the operation (all P < 0.05). Plasma albumin level was obviously effected by the operation and treatment (P = 0.006). The mean follow-up time was 72.5 months (57 - 102 months). No recurrence occurred during the follow-up. There was no patient died in 30 days after the operation. Seven cases (43.8%) died in the later period of follow-up. CONCLUSIONS: The tension-free repairing is feasible for the inguinal hernia complicated with cirrhosis and ascites. More attention should be paid to the level of plasma albumin and it should be corrected in time. The liver cirrhosis and its complications will progress after the operation with a poor prognosis.