Nanoreactor based on single-atom nanoenzymes promotes ferroptosis for cancer immunotherapy.

Immunotherapy is a promising mainstream approach in anti-tumor therapy. It boasts advantages such as durable responses and lower side effects. However, there are still some limitations to be addressed. Current cancer immunotherapy has shown low response rates due to inadequate immunogenicity of certain tumor cells. To address these challenges, an acid-specific nanoreactor was developed, designed to induce immunogenicity by triggering ferroptosis in tumor cells. The nanoreactor integrates glucose oxidase (GOx) with a single-atom nanoenzyme (SAE), which exhibits high peroxidase (POD)-like activity in the acidic tumor microenvironment (TME). This specific acid-sensitivity transforms endogenous hydrogen peroxide (H2O2) into cytotoxic hydroxyl radicals (•OH). GOx enhances the POD-like SAE activity in the nanoreactor by metabolizing glucose in tumor cells, producing gluconic acid and H2O2. This nanoreactor induces high levels of oxidative stress within tumor cells through the synergistic action of SAE and GOx, leading to depletion of GSH and subsequently triggering ferroptosis. The resulting nanoreactor-induced ferroptosis leads to immunogenic cell death (ICD) and significantly recruits T lymphocyte infiltration in tumor tissues. This study was designed with the concept of triggering ferroptosis-dependent ICD mechanism in bladder cancer cells, and developed an acid-specific nanoreactor to enhance the immunotherapy efficacy for bladder cancer, which introduces a novel approach for immunotherapy of bladder cancer.

Clinical and survival outcomes of colectomy for transverse colon cancer in elderly patients.

It remains controversial whether elderly patients with transverse colon cancer present worse prognoses. Our study utilized evidence from multi-center databases to evaluate the perioperative and oncology outcomes of radical resection of colon cancer in elderly and nonelderly patients. In this study, we analyzed 416 patients with transverse colon cancer who underwent radical surgery from January 2004 to May 2017, including 151 elderly (aged ≥ 65 years) and 265 nonelderly (aged < 65 years) patients. We retrospectively compared the perioperative and oncological outcomes between these 2 groups. The median follow-up in the elderly and nonelderly groups was 52 and 64 months, respectively. There were no significant differences in the overall survival (OS) (P = .300) and disease-free survival (DFS) (P = .380) between the elderly and nonelderly groups. However, the elderly group had longer hospital stays (P < .001), a higher complication rate (P = .027), and fewer lymph nodes harvested (P = .002). The N classification and differentiation were significantly associated with OS based on univariate analysis, and the N classification was an independent prognostic factor for OS based on multivariate analysis (P < .05). Similarly, the N classification and differentiation were significantly correlated with the DFS based on univariate analysis. However, multivariate analysis indicated that the N classification was an independent prognostic factor for DFS (P < .05). In conclusion, the survival and surgical outcomes in elderly patients were similar to nonelderly patients. The N classification was an independent factor for OS and DFS. Even though elderly patients with transverse colon cancer present a higher surgical risk than nonelderly patients, performing radical resection in elderly patients can be an appropriate choice for treatment.

Continuous Modulation of Electrocatalytic Oxygen Reduction Activities of Single-Atom Catalysts through p-n Junction Rectification.

Fine-tuning single-atom catalysts (SACs) to surpass their activity limit remains challenging at their atomic scale. Herein, we exploit p-type semiconducting character of SACs having a metal center coordinated to nitrogen donors (MeNx ) and rectify their local charge density by an n-type semiconductor support. With iron phthalocyanine (FePc) as a model SAC, introducing an n-type gallium monosulfide that features a low work function generates a space-charged region across the junction interface, and causes distortion of the FeN4 moiety and spin-state transition in the FeII center. This catalyst shows an over two-fold higher specific oxygen-reduction activity than that of pristine FePc. We further employ three other n-type metal chalcogenides of varying work function as supports, and discover a linear correlation between the activities of the supported FeN4 and the rectification degrees, which clearly indicates that SACs can be continuously tuned by this rectification strategy.

Estradiol Ameliorates Acute Kidney Ischemia-Reperfusion Injury by Inhibiting the TGF-ßRI-SMAD Pathway.

Renal ischemia-reperfusion injury (IRI) is less extensive in females than males in both animals and humans; however, this protection diminishes after menopause, suggesting that estrogen plays a pivotal role in IRI, but the underlying mechanism remains largely unknown. Our study found that 45 min of warm ischemia was sufficient to induce significant pathological changes without causing death in model animals. Compared with male rats, female rats exhibited less extensive apoptosis, kidney injury, and fibrosis; these effects were worsened in ovariectomized (OVX) rats and ameliorated upon estradiol (E2) supplementation. Furthermore, the levels of TGF-ßRI, but not TGF-ßRII or TGF-ß1, were significantly increased in OVX rats, accompanied by phosphorylated SMAD2/3 activation. Interestingly, the alteration trend of the nuclear ERα level was opposite that of TGF-ßRI. Furthermore, dual luciferase reporter and chromatin immunoprecipitation assays showed that ERα could bind to the promoter region of TGF-ßRI and negatively regulate its mRNA expression. Moreover, an in vitro study using NRK-52E cells showed that ERα knockdown blocked E2-mediated protection, while TGF-ßRI knockdown protected cells against hypoxic insult. The findings of this study suggest that renal IRI is closely related to the TGF-ßRI-SMAD pathway in females and that E2 exert its protective effect via the ERα-mediated transcriptional inhibition of TGF-ßRI expression.

Laparoscopic versus open radical resection for transverse colon cancer: evidence from multi-center databases.

BACKGROUND: The role of laparoscopic approach is still a controversy for transverse colon cancer. Our investigation aimed to evaluate the perioperative and oncologic outcomes of laparoscopic versus open radical resection for transverse colon cancer based on evidence from multi-center databases. METHODS: 416 patients with transverse colon cancer undergoing radical surgery were analyzed including 181 laparoscopic resections and 235 open resections from January 2004 to May 2017 based on multi-center databases. Perioperative and oncologic outcomes were compared. RESULTS: No statistical differences regarding the baseline characteristics were observed between the two groups except the procedure type. Compared with open approach, laparoscopic approach was associated with statistically longer operation time (209.96 vs. 173.31 min, P = 0.002), significantly shorter time to soft food intake (4.73 vs. 6.01 days, P = 0.034), and shorter postoperative hospitalization (12.05 vs. 14.44 days, P = 0.001). In terms of oncologic outcomes, laparoscopic resection was correlated with statistically more lymph node retrieval (13.52 vs. 15.91, P = 0.002) and similar 5-year overall survival (91.2% vs. 89.1%, P = 0.356) and disease-free survival (89.6% vs. 86.0%, P = 0.873), compared with open resection. CONCLUSIONS: For patients with transverse colon cancer, laparoscopic approach can achieve several short-term advantages without decreasing long-term oncologic survival.

MXene Surface Terminations Enable Strong Metal-Support Interactions for Efficient Methanol Oxidation on Palladium.

Efficient catalysis of the methanol oxidation reaction (MOR) greatly determines the widespread implementation of direct methanol fuel cells. Exploring a suitable support for noble metal catalysts with regard to decreasing the mass loading and optimizing the MOR activity remains a key challenge. Herein, we achieve an over 60% activity enhancement of a palladium (Pd) catalyst by introducing a two-dimensional Ti3C2Tx MXene as the support compared to a commercial Pd/C catalyst. Not only are more catalytically active Pd sites exposed on the Pd/MXene catalyst while maintaining a low mass loading, but the introduction of the MXene support also significantly alters the surface electronic structure of Pd. Specifically, spectroscopy and density functional theory (DFT) computations indicate that sufficiently electronegative terminations of the Ti3C2Tx MXene surface can induce strong metal-support interactions (SMSI) with the Pd catalyst, leading to optimal methanol adsorption. This MXene-supported Pd catalyst exhibits a much higher MOR current density (12.4 mA cm-2) than that of commercial Pd/C (7.6 mA cm-2). Our work largely optimizes the intrinsic activity of a Pd catalyst by the utilization of MXene surface terminations, and the crucial SMSI effects revealed herein open a rational avenue to the design of more efficient noble metal catalysts for MOR.

Prognostic and clinicopathological significance of CapG in various cancers: Evidence from a meta-analysis.

BACKGROUND: The gelsolin-like actin-capping protein (CapG) is an actin-binding protein in the gelsolin superfamily. Increasing evidence indicates that CapG is highly expressed in various types of cancer. However, the role of CapG in malignant tumors is still controversial. Therefore, we conducted a meta-analysis to assess the prognostic value and clinicopathological significance of CapG in malignant tumors. METHOD: We searched for eligible studies in the PubMed, Web of Science, Embase, and Cochrane databases. Stata SE12.0 software was used for quantitative meta-analysis. The hazard ratios (HRs) and odds ratios (ORs) with 95% CI were pooled to assess the relationship between CapG expression and overall survival (OS), as well as clinicopathological parameters. RESULTS: Sixteen studies with a total of 1987 cancer patients were included in this meta-analysis. The results showed that higher CapG expression was statistically correlated with shorter OS (HR 1.70, 95% CI 1.43-1.97, P < 0.001), positive lymph node metastasis (OR 1.91, 95% CI 1.19-3.09, P =  0.008), advanced TNM stage (OR 1.87, 95% CI 1.17-3.00, P = 0.009), advanced T-primary stage (OR 2.54, 95% CI 1.08-6.00, P =  0.033) and male sex (OR 1.77, 95% CI 1.23-2.56, P =  0.002). However, no significant correlation was observed between increased CapG expression and advanced age, larger tumor size, differentiation, or advanced histopathologic grading (P > 0.05). CONCLUSIONS: High CapG expression is associated with a poor prognosis and worse clinicopathological parameters in various cancers. CapG is a potential prognostic biomarker and a possible clinicopathological predictive factor for various cancers.

Prognostic and clinicopathological significance of kinesin family member C1 in various cancers: A meta-analysis.

BACKGROUND: Kinesin family member C1 (KIFC1), a C-type kinesin motor protein, plays important roles in centrosome assembly and intracellular transport. Numerous studies have focused on the prognostic value of KIFC1 in malignant tumors and the relationship between KIFC1 expression and clinicopathological traits of cancer patients, but the studies remain controversial. And no meta-analysis has yet shown the association between KIFC1 and various cancers. METHODS: Systematic retrieval was carried out within several databases, including PubMed, Embase, Web of Science, Wanfang and China National Knowledge Infrastructure (CNKI). In addition, hazard ratios (HR) and relative risks (RR) with 95% confidence intervals (CIs) were calculated to examine the risk or hazard correlation by Stata SE15.1. RESULTS: Eleven studies with the overall 2424 participants were included in this research. High KIFC1 expression was remarkably correlated with worse OS (HR = 1.33, 95% CI = 1.07-1.60) and poorer relapse-free survival (HR = 2.28, 95% CI = 1.75-2.80). In subgroup analysis, high KIFC1 expression was a negative predictor for OS in patients with ovarian cancer (P < .001), breast cancer (P < .001), hepatocellular carcinoma (P < .001), and non-small cell lung cancer (P < .001), but not for esophageal squamous cell carcinoma (P = .246). Moreover, high levels of KIFC1 were related with positive lymph node metastasis (RR = 1.23, 95% CI = 1.01-1.50, P = .041) and advanced tumor node metastasis (TNM) stage (RR = 1.55, 95% CI = 1.27-1.89, P < .001). CONCLUSIONS: KIFC1 overexpression indicates poor prognosis and more serious clinicopathological characteristics in kinds of malignancies. Thus, we conclude that KIFC1 could be a target for clinical diagnosis and treatment of various cancers.

Prognostic and clinicopathological significance of Cks1 in cancer: Evidence from a meta-analysis.

BACKGROUND: Cyclin-dependent kinase subunit 1 (Cks1), as a highly conserved regulatory protein, has pleiotropic roles in cell cycle progression. As research progresses, increasingly more statistics show that Cks1 may be involved in the occurrence, development, and prognosis of a variety of tumors but the conclusions remain controversial. In addition, there has been no meta-analysis demonstrating the correlation between Cks1 and cancer. Therefore, this meta-analysis was performed to determine the prognostic and clinicopathological significance of Cks1 in various cancers. METHODS: Systematic computer literature retrieval was conducted on the Web of Science, Embase, PubMed, CNKI, and Wanfang databases. Stata SE12.0 software was used in the quantitative meta-analysis. The hazard ratio (HR) and relative risk (RR) were pooled to assess the relationship between Cks1 expression and overall survival (OS), disease-free survival (DFS), and clinicopathological parameters. RESULTS: Nineteen studies were included, totaling 2,224 participants. High expression of Cks1 was significantly correlated with worse OS (HR, 2.62; 95% confidence interval [CI], 2.18-3.14; p < 0.001) and poorer DFS (HR, 2.73; 95% CI, 1.83-4.08; p < 0.001). In addition, high expression of Cks1 was related to lymph node metastasis (RR, 1.59; 95% CI, 1.22-2.07; p = 0.001) and advanced T stage (RR, 1.14; 95% CI, 1.04-1.25; p = 0.005). CONCLUSIONS: High Cks1 expression predicted poorer prognosis and worse clinicopathological parameters in various cancers. Increased Cks1 could be a significant prognostic biomarker for poor survival in patients with various cancers.

The Marriage of the FeN4 Moiety and MXene Boosts Oxygen Reduction Catalysis: Fe 3d Electron Delocalization Matters.

Iron-nitrogen-carbon (Fe-N-C) is hitherto considered as one of the most satisfactory alternatives to platinum for the oxygen reduction reaction (ORR). Major efforts currently are devoted to the identification and maximization of carbon-enclosed FeN4 moieties, which act as catalytically active centers. However, fine-tuning of their intrinsic ORR activity remains a huge challenge. Herein, a twofold activity improvement of pristine Fe-N-C through introducing Ti3 C2 Tx MXene as a support is realized. A series of spectroscopy and magnetic measurements reveal that the marriage of FeN4 moiety and MXene can induce remarkable Fe 3d electron delocalization and spin-state transition of Fe(II) ions. The lower local electron density and higher spin state of the Fe(II) centers greatly favor the Fe d z 2 electron transfer, and lead to an easier oxygen adsorption and reduction on active FeN4 sites, and thus an enhanced ORR activity. The optimized catalyst shows a two- and fivefold higher specific ORR activity than those of pristine catalyst and Pt/C, respectively, even exceeding most Fe-N-C catalysts ever reported. This work opens up a new pathway in the rational design of Fe-N-C catalysts, and reflects the critical influence of Fe 3d electron states in FeN4 moiety supported on MXene in ORR catalysis.

MoB/g-C3 N4 Interface Materials as a Schottky Catalyst to Boost Hydrogen Evolution.

Proton adsorption on metallic catalysts is a prerequisite for efficient hydrogen evolution reaction (HER). However, tuning proton adsorption without perturbing metallicity remains a challenge. A Schottky catalyst based on metal-semiconductor junction principles is presented. With metallic MoB, the introduction of n-type semiconductive g-C3 N4 induces a vigorous charge transfer across the MoB/g-C3 N4 Schottky junction, and increases the local electron density in MoB surface, confirmed by multiple spectroscopic techniques. This Schottky catalyst exhibits a superior HER activity with a low Tafel slope of 46 mV dec-1 and a high exchange current density of 17 µA cm-2 , which is far better than that of pristine MoB. First-principle calculations reveal that the Schottky contact dramatically lowers the kinetic barriers of both proton adsorption and reduction coordinates, therefore benefiting surface hydrogen generation.