Laparoscopic ileocecal-sparing vs traditional right hemicolectomy for cancer of the hepatic flexure or proximal transverse colon: a dual-center propensity score-matched study.

Background: Traditional right hemicolectomy (TRH) is the standard treatment for patients with nonmetastatic right colon cancer. However, the ileocecum, a vital organ with mechanical and immune functions, is removed in these patients regardless of the tumor location. This study aimed to evaluate the technical and oncological safety of laparoscopic ileocecal-sparing right hemicolectomy (LISH). Method: Patients who underwent LISH at two tertiary medical centers were matched 1:2 with patients who underwent TRH by propensity score matching based on sex, age, body mass index, tumor location, and disease stage. Data on surgical and perioperative outcomes were collected. Oncological safety was evaluated in a specimen-oriented manner. Lymph nodes (LNs) near the ileocolic artery (ICA) were examined independently in the LISH group. Disease outcomes were recorded for patients who completed one year of follow-up. Results: In all, 34 patients in the LISH group and 68 patients in the TRH group were matched. LISH added 8 minutes to the dissection of LNs around the ileocolic vessels (groups 201/201d, 202, and 203 LNs), without affecting the total operation time, blood loss, or perioperative adverse event rate. Compared with TRH, LISH had a comparable lymphadenectomy quality, specimen quality, and safety margin while preserving a more functional bowel. The LISH group had no cases of LN metastasis near the ICA. No difference was detected in the recurrence rate at the 1-year follow-up time point between the two groups. Conclusion: In this dual-center study, LISH presented comparable surgical and oncological safety for patients with hepatic flexure or proximal transverse colon cancer.

A New Dy(III) Complex: Fluorescence Performances, Loading with Resveratrol-Hydrogels Against Skin Aging and Molecular Docking.

In the present research, novel lanthanide coordination compounds [DyL(PhCOO)(CH3OH)](ClO4)2·(CH3OH)2 (1) were characterized by the compression of 2,6-diformyl-4-methyl-phenol (dmp) and 1,3-diamino-2-propanol using benzoate as the secondary ligand, where L indicates the deprotonated macrocyclic ligand. Through the high structural rigidity driven by the coordination of the macrocyclic ligand formed by condensation in methanol solution and sodium benzoate with Dy(ClO4)3·6H2O, compound 1 exhibits outstanding cyan-emitting fluorescence performance and potential applications as a fluorescent material. Additionally, hyaluronic acid (HA)/ carboxymethyl chitosan (CMCS) hydrogels were prepared with loaded resveratrol metal-organic complexes according to the synthetic chemical approach. In biological study, we evaluated the effect of hydrogels on oxidative stress on human dermal fibroblasts. Examined by molecular docking simulation, the results showed that the binding interactions were from the phenol group, the carboxyl group and also the "-N=" group, indicating Dy metal complex has excellent biological capability.

Hepatic steatosis predicts metachronous liver metastasis in colorectal cancer patients: a nested case-control study and systematic review.

Nearly twenty-five percent of colorectal cancer (CRC) patients develop metachronous colorectal liver metastasis (CRLM) after curative surgery. Hepatosteatosis is the most prevalent liver condition worldwide, but its impact on the incidence of metachronous CRLM is understudied. In the present study, we aimed to investigate the predictive value of hepatic steatosis on the development of metachronous CRLM. First, a nested case-control study was conducted, enrolling stage I to III CRC patients in the National Colorectal Cancer Cohort (NCRCC) database. Metachronous CRLM patients and recurrence-free patients were matched via propensity-score matching. Fatty liver was identified based on treatment-naïve CT scans and the degree of hepatic fibrosis was scored. Multivariable analysis was conducted to investigate the association between fatty liver and metachronous CRLM. In our database, a total of 414 patients were included. Metachronous CRLM patients had considerably higher rates of hepatic steatosis (30.9% versus 15.9%, P<0.001) and highly fibrotic liver (11.6% versus 2.9%, P=0.001) compared to recurrence-free patients. Multivariable analysis showed that fatty liver (odds ratios [OR]=1.99, 95% confidence interval [CI] 1.19-3.30, P=0.008) and fibrotic liver (OR=4.27, 95% CI 1.54-11.81, P=0.005) were associated with high risk of metachronous CRLM. Further, a systematic literature review was performed to assess available evidence on the association between hepatosteatosis and development of metachronous CRLM. In the systematic review, 1815 patients were pooled from eligible studies, and hepatic steatosis remained a significant risk factor for metachronous CRLM (OR=1.90, 95% CI 1.35-2.66, P<0.001, I2=25.3%). In conclusion, our data suggest that patients with a steatotic liver and a high fibrosis score at CRC diagnosis have elevated risk of developing metachronous CRLM.

Circulation immune cell landscape in canonical pathogenesis of colorectal adenocarcinoma by CyTOF analysis.

Current studies on the immune microenvironment of colorectal cancer (CRC) were mostly limited to the tissue level, lacking relevant studies in the peripheral blood, and failed to describe its alterations in the whole process of adenocarcinoma formation, especially of adenoma carcinogenesis. Here, we constructed a large-scale population cohort and used the CyTOF to explore the changes of various immune cell subsets in peripheral blood of CRC. We found monocytes and basophils cells were significantly higher in adenocarcinoma patients. Compared with early-stage CRC, effector CD4+T cells and naive B cells were higher in patients with lymph node metastasis, whereas the basophils were lower. We also performed random forest algorithm and found monocytes play the key role in carcinogenesis. Our study draws a peripheral blood immune cell landscape of the occurrence and development of CRC at the single-cell level and provides a reference for other researchers.

Comparative Analysis of Thiophene-Based Interlayer Cations for Enhanced Performance in 2D Ruddlesden-Popper Perovskite Solar Cells.

2D Ruddlesden-Popper (RP) perovskites have appeared as a promising prospective material owing to their tunable optoelectronic peculiarities and structural stability. The choice of interlayer cations greatly influences the performance of the 2D RP perovskites. In this study, through theoretical calculations and experimental investigation, we demonstrate the intrinsic and device performance differences between two perovskites based on cations of thiophenemethylamine (TMA) and thiopheneethylamine (TEA). Using density functional theory (DFT) calculations, it exposes that as compared to (TMA)2PbI4, (TEA)2PbI4 exhibits more pronounced distortion of [PbI6]4- units and possesses a wider band gap and larger effective mass. The experimental results on the TMA- and TEA-based 2D perovskites further show that when TEA is used as the interlayer cation, the crystallization process tends to form more low-n phases, which hinder charge transfer and decrease light harvesting. On the other hand, when TMA is used as the interlayer cation, excessive low-n phases are not observed, and the thin film exhibits excellent quality with significantly improved electron mobility. The (TMA)2(FA)n-1PbnI3n+1 (n = 5) perovskite device shows a remarkable conversion efficiency of 16.56%, much higher than that of TEA-based devices (PCE = 2.58%). Moreover, the unencapsulated devices based on TMA were able to maintain 88% of their initial efficiency even after being exposed to the environment (RT, RH = 30 ± 5%) for a duration of 1080 h. These findings provide important insights into the differences between thiophene-based cations and the selection of organic interlayer cations for 2D RP perovskite solar cells.

Lower rate of mpox vaccination hesitancy and medical consultation among Chinese men who have sex with men living with HIV in comparison with those living without HIV: A national observational study.

This anonymous cross-sectional study aimed to investigate the relationships between HIV infection and mpox-related focus issues among Chinese men who have sex with men (MSM). This study involved in 27 MSM social organizations and was conducted from July 31 to August 4, 2023. Mpox vaccination hesitancy was defined as the proportion of participants who expressed unwillingness to receive self-funded and free vaccines. Logistic regression models were employed to estimate odds ratios (OR) and 95% confidence interval (95%CI). Of 7196 MSMs, the prevalence of mpox differed between people living with HIV (PLWH) (1.04%, 20/1920) and people living without HIV (PLWoH) (0.55%, 29/5276) (P = .037). However, after adjusting for all covariates, there was no significant association between HIV status and mpox (aOR = 1.17; 95%CI = 0.58, 2.39; P = .658). Furthermore, the crude rates of vaccination hesitation (PLWoH: 5.91%, PLWH: 4.11%; P = .004) and consultation hesitation (PLWoH: 16.22%, PLWH: 10.78%; P < .001) were both lower in the PLWH. Compared with PLWoH, PLWH had lower odds ratios of vaccination hesitation (aOR = 0.70; 95%CI = 0.53, 0.92; P = .011) and consultation hesitation (aOR = 0.74; 95%CI = 0.60, 0.90; P = .003) among MSM. The estimate of association between HIV status and consultation hesitation was even smaller among MSM who reported hepatitis C infection or uncertainty (aOR = 0.30; 95%CI = 0.15, 0.56), compared with those without hepatitis C (aOR = 0.73; 95%CI = 0.60, 0.89) (P for interaction = .037). MSM living with HIV in China demonstrated a greater willingness to accept mpox vaccination and medical consultation. In the future, it is recommended that medical institutions establish good medical environment to control the mpox epidemic, especially for PLWH.

The prevalence of mpox and its association with sexual behavior among Chinese men who have sex with men in early August 2023.

Study investigating mpox infection and its association with sexual behavior among men who have sex with men (MSM) in China was lacking. This observational survey aimed to provide evidence on detail characteristics of mpox cases and sexual behavior, then analyze their relationship among MSM in China to help formulate prevention and control policies. An anonymous cross-sectional study was conducted in 27 MSM social organizations across 21 provinces, municipalities, and autonomous regions from July 31 to August 4, 2023. A safe sexual behavior index was constructed based on three risky sexual behaviors in the last month, including condomless anal intercourse, commercial sex and group sex. High safe sexual behavior indicated that the participant engaged in none of the three, and low safe sexual behavior indicated that they engaged in all three behaviors; otherwise, moderate safe sexual behavior was indicated. Among 7538 MSM, the prevalence of mpox was 0.73% (55/7538). The proportion of high safe sexual behavior was 79.64% (6003/7538). The crude prevalence of mpox was lower in the high safe sexual behavior group (0.35%, 21/6003), compared with the low (12.12%, 8/66) and moderate safe (1.78%, 26/1469) sexual behavior group. In the multivariable-adjusted analysis, after adjusting for all covariates, compared with low safe sexual behavior group, moderate safe sexual behavior group (aOR = 0.21; 95% CI = 0.08, 0.54) and high safe sexual behavior group (aOR = 0.04; 95% CI = 0.02, 0.12) both had lower risk of mpox. Of three sexual behaviors, MSM who reported no commercial sex had the lowest risk of mpox (aOR = 0.23; 95% CI = 0.13, 0.41), compared with those who reported commercial sex in the last month. The other two safe sexual behaviors both were associated with lower risk of mpox (no group sex vs. group sex: aOR = 0.15; 95% CI = 0.08, 0.28; no condomless anal intercourse vs. condomless anal intercourse: aOR = 0.23; 95% CI = 0.13, 0.41). The prevalence of mpox virus infection was nearly 1% among MSM in China. Strengthening mpox surveillance, emphasizing safe sexual behavior in health education are essential for the control of mpox among MSM in China.

Bandgap lowering in mixed alloys of Cs3Bi2-xSbxBr9 perovskite powders.

Lead-free metal halide perovskites have received widespread attention due to their composition of minimal hazardous components, excellent air stability, and long carrier lifetimes. However, the majority of the lead-free metal halide perovskites, such as Cs3Bi2Br9, have wide bandgaps, which limits their photoelectric in solar cells and optoelectronic devices. To address this issue, attempts have been made to adjust the bandgap through material alloying. Based on a solution approach, a pure phase of Cs3Bi2-xSbxBr9 crystals has been synthesized, with the alloying parameter x changing over the full range of composition. It is found that the mixed alloy has a smaller bandgap than pure Bi-based and Sb-based perovskites, with the smallest bandgap of 2.22 eV near x = 1, and there is a phenomenon of bandgap bowing throughout the alloying process. The electronic structure of Cs3Bi2-xSbxBr9 has been investigated using DFT calculations and the bandgap bowing of Cs3Bi2-xSbxBr9 is deduced to be related to the type-II band alignment between the Cs3Bi2Br9 and Cs3Sb2Br9. Owing to the mismatch of s and p orbital energies of Bi and Sb, the mixed alloy has a smaller bandgap. Our work demonstrated a method for achieving bandgap reduction and explained the phenomenon of bandgap bowing by pairing materials into type-II band alignment, which may also be found in other lead-free metal perovskites.

Mpox Vaccination Hesitancy and Its Associated Factors among Men Who Have Sex with Men in China: A National Observational Study.

More than 400 confirmed mpox cases have been reported in China. The mpox vaccination is crucial to mitigate mpox transmission, especially for at-risk populations. This study aimed to determine mpox vaccination hesitancy and its associated factors in Chinese men who have sex with men (MSM). This nationwide cross-sectional study was conducted among 7538 Chinese MSM in 27 MSM social organizations from 21 provinces, municipalities, and autonomous regions of China from 31 July to 4 August 2023. Of them, the rate of mpox vaccination hesitancy was 5.59% (421/7538). The most common reason for mpox vaccination hesitation was concerns of safety and side effects (62.71%, 264/421), followed by concerns of privacy (38.24%, 161/421), thoughts of impossible infection (37.53%, 158/421), no effectiveness in preventing reinfection (30.88%, 130/421), and no worry about infection (12.35%, 52/421). Regarding the concerning characteristics of the vaccines, concerns of vaccine safety ranked first (71.74%, 5408/7538), followed by vaccine effectiveness (14.05%, 1059/7538), vaccine costs (7.35%, 554/7538), and the continuity of vaccine effectiveness (3.91%, 295/7538). The highest odds ratio of mpox vaccination hesitation was seen in MSM who were infected with mpox virus (aOR = 2.38; 95%CI = 1.08, 5.23), followed by those aged ≥60 years (aOR = 2.25; 95%CI = 1.31, 3.88), those who were unemployed (aOR = 1.66; 95%CI = 1.25, 2.19), and those who had an education level of postgraduate and above (aOR = 1.55; 95%CI = 1.01, 2.37). However, MSM who had a higher level of mpox-related knowledge (moderate: aOR = 0.53; 95%CI = 0.36, 0.77; high: aOR = 0.30; 95%CI = 0.23, 0.40) had a lower odds ratio of mpox vaccination hesitation. MSM in China had low hesitancy toward mpox vaccination. The safety and effectiveness of the vaccine and privacy were important aspects of hesitancy. Health education on mpox-related knowledge should be encouraged to promote future vaccination plans.

A New Type of Endometrial Cancer Models in Mice Revealing the Functional Roles of Genetic Drivers and Exploring their Susceptibilities.

Endometrial cancer (EC) is the most common female reproductive tract cancer and its incidence has been continuously increasing in recent years. The underlying mechanisms of EC tumorigenesis remain unclear, and efficient target therapies are lacking, for both of which feasible endometrial cancer animal models are essential but currently limited. Here, an organoid and genome editing-based strategy to generate primary, orthotopic, and driver-defined ECs in mice is reported. These models faithfully recapitulate the molecular and pathohistological characteristics of human diseases. The authors names these models and similar models for other cancers as organoid-initiated precision cancer models (OPCMs). Importantly, this approach can conveniently introduce any driver mutation or a combination of driver mutations. Using these models,it is shown that the mutations in Pik3ca and Pik3r1 cooperate with Pten loss to promote endometrial adenocarcinoma in mice. In contrast, the Kras G12D mutati led to endometrial squamous cell carcinoma. Then, tumor organoids are derived from these mouse EC models and performed high-throughput drug screening and validation. The results reveal distinct vulnerabilities of ECs with different mutations. Taken together, this study develops a multiplexing approach to model EC in mice and demonstrates its value for understanding the pathology of and exploring the potential treatments for this malignancy.

Bidirectional Mendelian Randomisation Analysis Provides Evidence for the Causal Involvement of Dysregulation of CXCL9, CCL11 and CASP8 in the Pathogenesis of Ulcerative Colitis.

BACKGROUND AND AIMS: Systemic inflammation is well recognised to be associated with ulcerative colitis [UC], but whether these effects are causal or consequential remains unclear. We aimed to define potential causal relationship of cytokine dysregulation with different tiers of evidence. METHODS: We first synthesised serum proteomic profiling data from two multicentred observational studies, in which a panel of systemic inflammatory proteins was analysed to examine their associations with UC risk. To further dissect observed associations, we then performed a bidirectional two-sample Mendelian randomisation [TSMR] analysis from both forward and reverse directions using five genome-wide association study [GWAS] summary level data for serum proteomic profiles and the largest GWAS of 28 738 European-ancestry individuals for UC risk. RESULTS: Pooled analysis of serum proteomic data identified 14 proteins to be associated with the risk of UC. Forward MR analysis using only cis-acting protein quantitative trait loci [cis-pQTLs] or trans-pQTLs further validated causal associations of two chemokines and the increased risk of UC: C-X-C motif chemokine ligand 9 [CXCL9] [OR 1.45, 95% CI 1.08, 1.95, p = 0.012] and C-C motif chemokine ligand 11 [CCL11] [OR 1.14, 95% CI 1.09, 1.18, p = 3.89 × 10-10]. Using both cis- and trans-acting pQTLs, an association of caspase-8 [CASP8] [OR 1.04, 95% CI 1.03, 1.05, p = 7.63 × 10-19] was additionally identified. Reverse MR did not find any influence of genetic predisposition to UC on any of these three inflammation proteins. CONCLUSION: Pre-existing elevated levels of CXCL9, CCL11 and CASP8 may play a role in the pathogenesis of UC.

Acquired semi-squamatization during chemotherapy suggests differentiation as a therapeutic strategy for bladder cancer.

Cisplatin-based chemotherapy remains the primary treatment for unresectable and metastatic muscle-invasive bladder cancers (MIBCs). However, tumors frequently develop chemoresistance. Here, we established a primary and orthotopic MIBC mouse model with gene-edited organoids to recapitulate the full course of chemotherapy in patients. We found that partial squamous differentiation, called semi-squamatization, is associated with acquired chemoresistance in both mice and human MIBCs. Multi-omics analyses showed that cathepsin H (CTSH) is correlated with chemoresistance and semi-squamatization. Cathepsin inhibition by E64 treatment induces full squamous differentiation and pyroptosis, and thus specifically restrains chemoresistant MIBCs. Mechanistically, E64 treatment activates the tumor necrosis factor pathway, which is required for the terminal differentiation and pyroptosis of chemoresistant MIBC cells. Our study revealed that semi-squamatization is a type of lineage plasticity associated with chemoresistance, suggesting that differentiation via targeting of CTSH is a potential therapeutic strategy for the treatment of chemoresistant MIBCs.

Tumor-associated macrophages are shaped by intratumoral high potassium via Kir2.1.

The tumor microenvironment (TME) is a unique niche governed by constant crosstalk within and across all intratumoral cellular compartments. In particular, intratumoral high potassium (K+) has shown immune-suppressive potency on T cells. However, as a pan-cancer characteristic associated with local necrosis, the impact of this ionic disturbance on innate immunity is unknown. Here, we reveal that intratumoral high K+ suppresses the anti-tumor capacity of tumor-associated macrophages (TAMs). We identify the inwardly rectifying K+ channel Kir2.1 as a central modulator of TAM functional polarization in high K+ TME, and its conditional depletion repolarizes TAMs toward an anti-tumor state, sequentially boosting local anti-tumor immunity. Kir2.1 deficiency disturbs the electrochemically dependent glutamine uptake, engendering TAM metabolic reprogramming from oxidative phosphorylation toward glycolysis. Kir2.1 blockade attenuates both murine tumor- and patient-derived xenograft growth. Collectively, our findings reveal Kir2.1 as a determinant and potential therapeutic target for regaining the anti-tumor capacity of TAMs within ionic-imbalanced TME.

KMT2C deficiency promotes small cell lung cancer metastasis through DNMT3A-mediated epigenetic reprogramming.

Small cell lung cancer (SCLC) is notorious for its early and frequent metastases, which contribute to it as a recalcitrant malignancy. To understand the molecular mechanisms underlying SCLC metastasis, we generated SCLC mouse models with orthotopically transplanted genome-edited lung organoids and performed multiomics analyses. We found that a deficiency of KMT2C, a histone H3 lysine 4 methyltransferase frequently mutated in extensive-stage SCLC, promoted multiple-organ metastases in mice. Metastatic and KMT2C-deficient SCLC displayed both histone and DNA hypomethylation. Mechanistically, KMT2C directly regulated the expression of DNMT3A, a de novo DNA methyltransferase, through histone methylation. Forced DNMT3A expression restrained metastasis of KMT2C-deficient SCLC through repressing metastasis-promoting MEIS/HOX genes. Further, S-(5'-adenosyl)-L-methionine, the common cofactor of histone and DNA methyltransferases, inhibited SCLC metastasis. Thus, our study revealed a concerted epigenetic reprogramming of KMT2C- and DNMT3A-mediated histone and DNA hypomethylation underlying SCLC metastasis, which suggested a potential epigenetic therapeutic vulnerability.

Identifying a confused cell identity for esophageal squamous cell carcinoma.

The cell identity of malignant cells and how they acquire it are fundamental for our understanding of cancer. Here, we report that esophageal squamous cell carcinoma (ESCC) cells display molecular features equally similar but distinct to all three types of normal esophageal epithelial cells, which we term as confused cell identity (CCI). CCI is an independent prognostic marker associated with poor prognosis in ESCC. Further, we identify tropomyosin 4 (TPM4) as a critical CCI gene that promotes the aggressiveness of ESCC in vitro and in vivo. And TPM4 creates CCI through activating the Jak/STAT-SOX2 pathway. Thus, our study suggests an unrecognized feature of ESCC cells, which might be of value for clinic prognosis and potential interference.

The growth pattern of liver metastases on MRI predicts early recurrence in patients with colorectal cancer: a multicenter study.

OBJECTIVES: The multicenter study aimed to explore the relationship between the growth pattern of liver metastases on preoperative MRI and early recurrence in patients with colorectal cancer liver metastases (CRCLM) after surgery. METHODS: A total of 348 CRCLM patients from 3 independent centers were enrolled, including 130 patients with 339 liver metastases in the primary cohort and 218 patients in validation cohorts. Referring to the gross classification of hepatocellular carcinoma (HCC), the growth pattern of each liver metastasis on MRI was classified into four types: rough, smooth, focal extranodular protuberant (FEP), and nodular confluent (NC). Disease-free survival (DFS) curve was constructed using the Kaplan-Meier method. RESULTS: In primary cohort, 42 (12.4%) of the 339 liver metastases were rough type, 237 (69.9%) were smooth type, 29 (8.6%) were FEP type, and 31 (9.1%) were NC type. Those patients with FEP- and/or NC-type liver metastases had shorter DFS than those without such metastases (p < 0.05). However, there were no significant differences in DFS between patients with rough- and smooth-type liver metastases and those without such metastases. The patients with FEP- and/or NC-type liver metastases also had shorter DFS than those without such metastases in two external validation cohorts. In addition, 40.5% of high-risk-type (FEP and NC) liver metastases converted to low-risk types (rough and smooth) after neoadjuvant chemotherapy. CONCLUSION: The FEP- and NC-type liver metastases were associated with early recurrence, which may facilitate the clinical treatment of CRCLM patients. KEY POINTS: • In the primary cohort, patients with FEP- and NC-type metastases had shorter disease-free survival (DFS) and a higher intrahepatic recurrence rate than patients without such metastases in the liver. • In the primary cohort, there were no significant differences in DFS or intrahepatic recurrence rate between patients with rough- and smooth-type metastases and those without such metastases in the liver. • High-risk patients had shorter DFS and a higher intrahepatic recurrence rate than low-risk patients in primary and external validation cohorts.

Tumor enhancement ratio on preoperative abdominal contrast-enhanced CT scan for predicting recurrence risk in stage II colon cancer.

PURPOSE: The identification of high recurrence risk stage II colon cancer patients was critical to adjuvant chemotherapy decision. However, current definition of high-risk features remains inadequate. This study aimed to construct a model for predicting recurrence risk based on tumor enhancement ratio (TER) on abdominal contrast-enhanced CT scan. METHOD: 282 stage II colon cancer patients were included and randomly divided into training and validation sets in the ratio of 7:3. TER was calculated using maximum tumor attenuation value in contrast-enhanced CT scan divided by the minimum. Kaplan-Meier survival analyses were adopted to evaluate the prognostic value of variables. A model based on TER was built to predict recurrence risk through the LASSO Cox model. The recurrence risk score of patients was calculated based on this model. RESULTS: The optimal cut-off value of TER was 1.83 derived from the time-dependent ROC (tdROC) curve. Patients with high-TER showed increasingly poorer disease-free survival (DFS) in both training (p < 0.001) and validation (p < 0.001) sets. A model was built based on TER demonstrated satisfactory performance to recurrence risk prediction (C-index: 0.784 in the training set and 0.725 in the validation set). Patients were regrouped into modified high-risk and non-high risk according to recurrence risk score (cut-off value: 1.75) and a significant DFS difference was observed (training set: p < 0.001; validation set: p < 0.001). CONCLUSION: TER can serve as a high-risk feature of stage II colon cancer. And a model based on TER provided a new approach to assess recurrence risk of stage II disease.

Zinc Oxide Nanoparticles Prime a Protective Immune Response in Galleria mellonella to Defend Against Candida albicans.

Purpose: Zinc oxide nanoparticles (ZnO-NPs) have exerted antimicrobial properties. However, there is insufficient evaluation regarding the in vivo antifungal activity of ZnO-NPs. This study aimed to investigate the efficacy and mechanism of ZnO-NPs in controlling Candida albicans in the invertebrate Galleria mellonella. Methods: Galleria mellonella larvae were injected with different doses of ZnO-NPs to determine their in vivo toxicity. Non-toxic doses of ZnO-NPs were chosen for prophylactic injection in G. mellonella followed by C. albicans infection. Then the direct in vitro antifungal effect of ZnO-NPs against C. albicans was evaluated. In addition, the mode of action of ZnO-NPs was assessed in larvae through different assays: quantification of hemocyte density, morphology observation of hemocytes, characterization of hemocyte aggregation and phagocytosis, and measurement of hemolymph phenoloxidase (PO) activity. Results: Zinc oxide nanoparticles were non-toxic to the larvae at relatively low concentrations (≤20 mg/kg). ZnO-NP pretreatment significantly prolonged the survival of C. albicans-infected larvae and decreased the fungal dissemination and burden in the C. albicans-infected larvae. This observation was more related to the activation of host defense rather than their fungicidal capacities. Specifically, ZnO-NP treatment increased hemocyte density, promoted hemocyte aggregation, enhanced hemocyte phagocytosis, and activated PO activity in larvae. Conclusion: Prophylactic treatment with lower concentrations of ZnO-NPs protects G. mellonella from C. albicans infection. The innate immune response primed by ZnO-NPs may be part of the reason for the protective effects. This study provides new evidence of the capacity of ZnO-NPs in enhancing host immunity and predicts that ZnO-NPs will be attractive for further anti-infection applications.

Constructing the ceRNA Regulatory Network and Combining Immune Cells to Evaluate Prognosis of Colon Cancer Patients.

Objective: This study was conducted in order to construct a competitive endogenous RNA (ceRNA) network to screen RNA that plays an important role in colon cancer and to construct a model to predict the prognosis of patients. Methods: The gene expression data of colon cancer were downloaded from the TCGA database. The difference was analyzed by the R software and the ceRNA network was constructed. The survival-related RNA was screened out by combining with clinical information, and the prognosis model was established by lasso regression. CIBERSORT was used to analyze the infiltration of immune cells in colon cancer, and the differential expression of immune cells related to survival was screened out by combining clinical information. The correlation between RNA and immune cells was analyzed by lasso regression. PCR was used to verify the expression of seven RNAs in colon cancer patients with different prognoses. Results: Two hundred and fifteen lncRNAs, 357 miRNAs, and 2,955 mRNAs were differentially expressed in colon cancer. The constructed ceRNA network contains 18 lncRNAs, 42 miRNAs, and 168 mRNAs, of which 18 RNAs are significantly related to survival. Through lasso analysis, we selected seven optimal RNA construction models. The AUC value of the model was greater than 0.7, and there was a significant difference in the survival rate between the high- and low-risk groups. Two kinds of immune cells related to the prognosis of patients were screened out. The results showed that the expression of seven RNA markers in colon cancer patients with different prognoses was basically consistent with the model analysis. Conclusion: We have established the regulatory network of ceRNA in colon cancer, screened out seven core RNAs and two kinds of immune cells, and constructed a comprehensive prognosis model of colon cancer patients.