Commensal microbiota-derived metabolite agmatine triggers inflammation to promote colorectal tumorigenesis.

Colorectal cancer (CRC), a malignant tumor worldwide, is associated with gut microbiota. The influence of gut microbe-derived metabolites on CRC has attracted a lot of attention. However, the role of immunity mediated by commensal microbiota-derived metabolites in tumorigenesis of CRC is not intensively explored. Here we monitored the gut microbial dysbiosis in CRC mouse model (ApcMin/+ model) without dietary and pharmacological intervention, followed by characterized of metabolites enriched in CRC model mice. Profound changes of gut microbiome (bacteriome) were observed during intestinal disorders. Metabolomic profiling indicated that agmatine, derived from the gut bacteria i.e. Blautia, Odoribacter, Alistipes and Paraprevotella, could interact with Rnf128 to suppress the Rnf128-mediated ubiquitination of ß-catenin to further upregulate the downstream targets of ß-catenin including Cyclin D1, Lgr5, CD44 and C-myc, thus activating Wnt signaling. The activated Wnt signaling pathway promoted dysplasia of intestinal cells and inflammatory infiltration of lymphocytes via inducing the upregulation of pro-inflammatory cytokines (IL-6 and TNF-α) and downregulation of anti-inflammatory cytokine (IL-10), thereby contributing to colorectal carcinogenesis. Therefore, our study presented novel insights into the roles and mechanisms of gut microbiota in pathogenesis of CRC.

PAX1/JAM3 Methylation and HPV Viral Load in Women with Persistent HPV Infection.

The relationship of PAX1/JAM3 methylation as well as HPV viral load (VL) with cervical lesions has been reported, but their role in persistent HPV infection without cervical high-grade lesions has not been fully elucidated. A total of 231 females diagnosed with persistent HPV infection and pathologically confirmed absence of high-grade cervical lesions were selected from the Colposcopy Outpatient Clinic of Peking University People's Hospital, from March 2023 to December 2023. They were categorized into two groups based on the duration of HPV infection: the HPV persistent less than 3 years group and the more than 3 years group. PAX1/JAM3 methylation and HPV VL were determined by real-time PCR and BioPerfectus Multiplex Real-Time (BMRT)-HPV reports type-specific VL/10,000 cells, respectively. The average age of individuals with HPV infection lasting more than 3 years was higher compared to those with less than 3 years (48.9 vs. 45.1 years), with a statistically significant difference. Among the participants, 81.8% (189/231) had no previous screening. The methylation levels of JAM3 and PAX1 were significantly higher in individuals with HPV infection persisting for more than 3 years compared to those with less than 3 years, with a statistically significant difference (p < 0.05). There was a significant correlation between PAX1 and JAM3 methylation (p < 0.001), which could be used as cumulative evidence of HPV infection duration before the occurrence of precancerous lesions. The incidence of vaginal intraepithelial lesions was higher in individuals with HPV infection persisting for more than 3 years compared to those with less than 3 years, and HPV VL can be used as an indicative biomarker for concurrent cervical-vaginal lesions, especially for HPV other than 16/18 genotypes.

Methylated lncRNAs suppress apoptosis of gastric cancer stem cells via the lncRNA-miRNA/protein axis.

BACKGROUND: Long noncoding RNAs (lncRNAs) play essential roles in the tumorigenesis of gastric cancer. However, the influence of lncRNA methylation on gastric cancer stem cells (GCSCs) remains unclear. METHODS: The N6-methyladenosine (m6A) levels of lncRNAs in gastric cancer stem cells were detected by methylated RNA immunoprecipitation sequencing (MeRIP-seq), and the results were validated by MeRIP-quantitative polymerase chain reaction (qPCR). Specific sites of m6A modification on lncRNAs were detected by single-base elongation- and ligation-based qPCR amplification (SELECT). By constructing and transfecting the plasmid expressing methyltransferase-like 3 (METTL3) fused with catalytically inactivated Cas13 (dCas13b) and guide RNA targeting specific methylation sites of lncRNAs, we obtained gastric cancer stem cells with site-specific methylation of lncRNAs. Reverse transcription (RT)-qPCR and Western blot were used for detecting the stemness of treated gastric cancer stem cells. RESULTS: The site-specific methylation of PSMA3-AS1 and MIR22HG suppressed apoptosis and promoted stemness of GCSCs. LncRNA methylation enhanced the stability of PSMA3-AS1 and MIR22HG to suppress apoptosis of GCSCs via the PSMA3-AS1-miR-411-3p- or MIR22HG-miR-24-3p-SERTAD1 axis. Simultaneously, the methylated lncRNAs promoted the interaction between PSMA3-AS1 and the EEF1A1 protein or MIR22HG and the LRPPRC protein, stabilizing the proteins and leading to the suppression of apoptosis. The in vivo data revealed that the methylated PSMA3-AS1 and MIR22HG triggered tumorigenesis of GCSCs. CONCLUSIONS: Our study revealed the requirement for site-specific methylation of lncRNAs in the tumorigenesis of GCSCs, contributing novel insights into cancer development.

Bilateral Inferior Petrosal Sinus Sampling Without Lateralization Is Less Accurate for the Diagnosis of Cushing Disease.

Context: During bilateral inferior petrosal sinus sampling (BIPSS), the side-to-side adrenocorticotropic hormone (ACTH) ratio, referred to as sampling lateralization, was used to predict pituitary adenoma localization. Objective: To investigate the potential different diagnostic accuracy of BIPSS for differentiating Cushing disease (CD) and ectopic ACTH secretory syndrome (EAS) patients with low lateralization (inferior petrosal sinus [IPS]:IPS ≤ 1.4) and high lateralization (IPS:IPS > 1.4). Methods: This single-center retrospective study (2011-2021) included (all patients had BIPSS results and confirmed pathologic diagnoses) 220 consecutive CD patients (validation set), 30 EAS patients, and 40 of the CD patients who had digital subtraction angiography (DSA) videos (discovery set). Results: In the discovery set, the low-lateralization CD group (n = 11) had a higher median plasma ACTH concentration (62.2, IQR 44.7-181.0 ng/L) than the high-lateralization CD group (n = 29) (33.0, IQR 18.5-59.5, P = .013). Lower IPS to peripheral ratios were observed in the low-lateralization group during BIPSS, both before and after stimulation (P = .013 and P = .028). The sensitivity of BIPSS before stimulation in differentiating CD from EAS was lower in the low-lateralization group than the high-lateralization group (54.6% vs 93.1%, P = .003), as validated in the validation set. DSA videos revealed higher vascular area difference visible in the 2 sides of the pituitary in low lateralization (median 1.2 × 105 pixels, IQR 0.5-1.8) than the high-lateralization group (0.4 × 105 pixels, IQR 0.1-0.7, P = .008). The vascular area ratio of the 2 sides was also significantly higher in low (1.55, IQR 1.31-2.20) than high lateralization (1.19, IQR 1.07-1.35, P = .010). Conclusion: Our study suggested that low lateralization in CD patients may reduce the diagnostic sensitivity of BIPSS, which might be potentially associated with peripituitary vascular anatomy.

Incidence and analysis of intraoperative complications in femtosecond laser-assisted cataract surgery: a large-scale cohort study to establish the learning curve.

AIMS: To assess the safety of femtosecond laser-assisted cataract surgery (FLACS) based on surgical parameters and intraoperative complications analysis and to determine the length of the learning curve for FLACS. METHODS: A prospective consecutive cohort study was conducted on Chinese patients who underwent either FLACS (3289 cases) or contemporaneous conventional phacoemulsification cataract surgery (2130 cases). The laser group was divided into four subgroups in chronological order. We recorded intraoperative complication incidences and compared with surgical parameters between groups. Subgroup analysis was conducted to explore the learning curve of FLACS. RESULTS: The laser group had a 4.93% incidence of incomplete capsulotomies and a 1.22% incidence of anterior capsule tears. Subgroup analysis showed significant differences in 8 aspects between the first 250 cases (50 cases per surgeon) and the last 2539 cases, but only 2 aspects differed between the second 250 cases (50 cases per surgeon) and the last 2539 cases. There were no significant differences between the third 250 cases (50 cases per surgeon) and the last 2539 cases. CONCLUSIONS: The intraoperative complications of FLACS were reported, and the learning curve is associated with a significant reduction in the incidence of intraoperative complications. The length of the basic learning curve of FLACS is 100 cases, and the length of the advanced learning curve was 150 cases. This study demonstrated that FLACS is characterised by a relatively straightforward and secure operative technique.

Checkpoint CD24 function on tumor and immunotherapy.

CD24 is a protein found on the surface of cells that plays a crucial role in the proliferation, invasion, and spread of cancer cells. It adheres to cell membranes through glycosylphosphatidylinositol (GPI) and is associated with the prognosis and survival rate of cancer patients. CD24 interacts with the inhibitory receptor Siglec-10 that is present on immune cells like natural killer cells and macrophages, leading to the inhibition of natural killer cell cytotoxicity and macrophage-mediated phagocytosis. This interaction helps tumor cells escape immune detection and attack. Although the use of CD24 as a immune checkpoint receptor target for cancer immunotherapy is still in its early stages, clinical trials have shown promising results. Monoclonal antibodies targeting CD24 have been found to be well-tolerated and safe. Other preclinical studies are exploring the use of chimeric antigen receptor (CAR) T cells, antibody-drug conjugates, and gene therapy to target CD24 and enhance the immune response against tumors. In summary, this review focuses on the role of CD24 in the immune system and provides evidence for CD24 as a promising immune checkpoint for cancer immunotherapy.

Tumor microenvironment characteristics and prognostic role of m6A modification in lung squamous cell carcinoma.

Background: It has recently been determined that N6-methyladenosine (m6A) RNA methylation regulators have prominent effects on several cancers. However, the potential role of m6A modification in lung squamous cell carcinoma (LUSC) remains unclear. Methods: We evaluated the modification pattern of m6A and studied the biological function of m6A regulators in LUSC. Then, we constructed the m6Ascore to predict the prognosis of LUSC and analyzed the relationship between the m6Ascore and tumor mutation burden, immune cell infiltration, and immunotherapy. Result: In the unsupervised consensus cluster analysis, three different m6Aclusters were identified, which correspond to an immune activation state, a moderate immune activation state, and an immune tolerance state. Forty-two genes related to the m6A phenotype were used to construct the m6Ascore; subsequently, multiple validations of the m6Ascore were carried out to determine the relationship between the score and immune cell infiltration and response to CTLA-4/PD-1 inhibitor treatment. Further analysis revealed that the m6Ascore could effectively predict the prognosis of LUSC and that the m6A phenotype-related genes, FAM162A and LOM4, might be potential biomarkers. Conclusion: These findings highlight the potential role of m6A modification in the prognosis, TME, and immunotherapy of LUSC and have profound implications for developing more effective personalized treatment strategies for LUSC.

[Zhuyu Pills promote polarization of macrophages toward M2 phenotype to prevent atherosclerosis via PPARγ/NF-κB signaling pathway].

This article aims to investigate the effect of Zhuyu Pills on atherosclerosis and decipher the underlying mechanism. The mouse model of atherosclerosis was induced by a high-fat diet, and the total modeling period was 12 weeks. A total of 47 ApoE~(-/-) mice successfully modeled were randomized into 5 groups, including 10 in the model group, 9 in each of low-, medium-, and high-dose(130.54, 261.08 and 522.16 mg·kg~(-1)·d~(-1), respectively) Zhuyu Pills groups, and 10 in the atorvastatin calcium(10.40 mg·kg~(-1)·d~(-1)) group. In addition, 10 C57BL/6J mice were included as the normal group. The mice in the normal group and model group were administrated with an equal volume of sterile distilled water, and those in other groups with corresponding agents by gavage once a day for 12 weeks. At the end of drug intervention, the levels of total cholesterol(TC), triglyceride(TG), high-density lipoprotein cholesterol(HDL-C), and low-density lipoprotein cholesterol(LDL-C) were measured by the biochemical method. Hematoxylin-eosin(HE) staining was employed to observe the plaque distribution in the aortic region. The serum levels of pro-inflammatory cytokines tumor necrosis factor-α(TNF-α) and interleukin(IL)-6 in M1 macrophages and anti-inflammatory cytokines IL-13 and IL-4 in M2 macrophages were determined by enzyme-linked immunosorbent assay(ELISA). The expression levels of inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1) were examined by immunofluorescence. Real-time fluorescence quantitative polymerase chain reaction(real-time PCR) was employed to measure the mRNA levels of peroxisome proliferator-activated receptor γ(PPARγ), nuclear factor-κB(NF-κB), Arg-1, and iNOS in the aorta. Western blot was employed to determine the protein levels of PPARγ and NF-κB in the aorta. The results showed that compared with the normal group, the modeling elevated the TC, TG, and LDL-C levels, lowered the HDL-C level, caused large area thickening of the aortic intima, elevated the TNF-α and IL-6 levels, lowered the IL-4 and IL-13 levels, down-regulated the mRNA and protein levels of PPARγ and Arg-1, and up-regulated the mRNA and protein levels of iNOS and NF-κB in the aorta(P<0.01). Compared with the model group, low-, medium-, and high-dose Zhuyu Pills and atorvastatin calcium lowered the TC, TG, and LDL-C levels, elevated the HDL-C level, reduced the plaque area in a concentration-dependent manner, lowered the TNF-α and IL-6 levels, elevated the IL-4 and IL-13 levels, up-regulated the mRNA and protein levels of PPARγ and Arg-1, and down-regulated the mRNA and protein levels of NF-κB and iNOS in the aorta(P<0.05 or P<0.01). In conclusion, Zhuyu Pills may play an anti-atherosclerosis role by regulating PPARγ/NF-κB signaling pathway, inhibiting the polarization of macrophages toward the M1 phenotype, promoting the polarization of macrophages toward the M2 phenotype, and improving the inflammatory microenvironment of macrophages.

Comparison of instrumented and stand-alone lateral lumbar interbody fusion for lumbar degenerative disease: a systematic review and meta-analysis.

BACKGROUND: Both instrumented and stand-alone lateral lumbar interbody fusion (LLIF) have been widely used to treat lumbar degenerative disease. However, it remains controversial as whether posterior internal fixation is required when LLIF is performed. This meta-analysis aims to compare the radiographic and clinical results between instrumented and stand-alone LLIF. METHODS: PubMed, EMBASE and Cochrane Collaboration Library up to March 2023 were searched for studies that compared instrumented and stand-alone LLIF in the treatment of lumbar degenerative disease. The following outcomes were extracted for comparison: interbody fusion rate, cage subsidence rate, reoperation rate, restoration of disc height, segmental lordosis, lumbar lordosis, visual analog scale (VAS) scores of low-back and leg pain and Oswestry Disability Index (ODI) scores. RESULTS: 13 studies involving 1063 patients were included. The pooled results showed that instrumented LLIF had higher fusion rate (OR 2.09; 95% CI 1.16-3.75; P = 0.01), lower cage subsidence (OR 0.50; 95% CI 0.37-0.68; P < 0.001) and reoperation rate (OR 0.28; 95% CI 0.10-0.79; P = 0.02), and more restoration of disc height (MD 0.85; 95% CI 0.18-1.53; P = 0.01) than stand-alone LLIF. The ODI and VAS scores were similar between instrumented and stand-alone LLIF at the last follow-up. CONCLUSIONS: Based on this meta-analysis, instrumented LLIF is associated with higher rate of fusion, lower rate of cage subsidence and reoperation, and more restoration of disc height than stand-alone LLIF. For patients with high risk factors of cage subsidence, instrumented LLIF should be applied to reduce postoperative complications.

A biomimetic nanocarrier facilitates glucose consumption and reactive oxide species accumulation in enzyme therapy for colorectal cancer.

Glucose oxidase (GOx)-based enzyme therapeutics are potential alternatives for colorectal cancer (CRC) treatment via glucose consumption and accumulation of hydrogen peroxide (H2O2). Given that H2O2 can be eliminated by cytoprotective autophagy, autophagy inhibitors that can interrupt autolysosome-induced H2O2 elimination are promising combination drugs of GOx. Here, we developed a multifunctional biomimetic nanocarrier for effective co-delivery of an autophagy inhibitor-chloroquine phosphate (CQP) and GOx to exert their synergistic effect by irreversibly upregulating intracellular reactive oxygen species (ROS) levels. Poly (D, l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) were used to encapsulate both GOx and CQP using a W/O/W multi-emulsion method. Calcium phosphate (CaP) was used to "fix" CQP to GOx in the internal water phase, where it served as a pH-sensitive unit to facilitate intracellular drug release. Folic acid-modified red blood cell membranes (FR) were used to camouflage the GOx/CQP/CaP encapsulated PLGA NPs (referred to as PLGA/GCC@FR). In an AOM/DSS-induced CRC mouse model, PLGA/GCC@FR exhibited improved antitumor effects, in which the number of tumor nodes were only a quarter of that in the free drug combination group. The enhanced therapeutic effects of PLGA/GCC@FR were attributed to the prolonged tumor retention which was verified by both dynamic in vivo imaging and drug biodistribution. This multifunctional biomimetic nanocarrier facilitated combined enzyme therapeutics by depleting glucose and augmenting intracellular ROS levels in tumor cells, which exerted a synergistic inhibitory effect on tumor growth. Therefore, this study proposed a novel strategy for the enhancement of combined enzyme therapeutics, which provided a promising method for effective CRC treatment.

Validation of a one-step genomics-based molecular classifier for endometrial carcinoma in a large Chinese population.

OBJECTIVE: The aim of this study is to delineate the molecular classification features within Chinese endometrial cancer (EC) patients and to evaluate the concurrence between two widely employed methods for diagnosing EC molecular subtypes. METHODS: This retrospective observational cohort study encompassed 479 cases of EC for analysis. Utilizing next-generation sequencing (NGS) panels targeting POLE, TP53, and microsatellite instability (MSI) status, four subtypes [POLE ultramutated (POLE mut), MMR-deficient (MMRd), p53 abnormal (p53abn), and no specific molecular profile (NSMP)] were classified. Immunohistochemistry (IHC) was employed to ascertain the expression of p53 and MMR proteins. RESULTS: Among the 479 patients, the distribution of EC subtypes was as follows: 28 (5.85%) POLE mut, 67 (13.99%) MMRd, 60 (12.53%) p53abn, and 324 (67.64%) NSMP. When compared to published findings on EC subtypes in the Caucasian population, our real-world data on Chinese ECs revealed a notably higher proportion of NSMP/CNL (copy number low). The evaluation of MSI/MMR status through NGS-based and IHC-based methods displayed substantial concordance (Kappa = 0.91). Slight discordance between the two techniques in identifying p53 abnormalities (Kappa = 0.83) might stem from TP53 truncating mutations, cytoplasmic p53 expression, null TP53 mutants, and well-documented challenges in interpreting p53 IHC. CONCLUSIONS: Chinese ECs exhibit distinctive molecular attributes. For accurate molecular subtyping of Chinese ECs, additional molecular markers that align with the Chinese population's characteristics should be incorporated into existing classifiers. The study's outcomes underscore a strong agreement between NGS and IHC in TP53/p53 detection and MSI assessment.

CT-guided Percutaneous Microwave Ablation Combined with Local Radiotherapy or Chemotherapy of Malignant Pulmonary Tumors.

BACKGROUND AND OBJECTIVE: The study aimed to investigate the clinical efficacy of CT-guided microwave ablation (MWA) combined with 125I seed implantation or bronchial arterial infusion (BAI) chemotherapy in the treatment of malignant pulmonary tumors. METHODS: A total of 56 patients who underwent MWA, MWA combined with 125I particle implantation, or MWA combined with BAI chemotherapy for advanced lung cancer or metastatic lung cancer from January 2015 to June 2021 in Guangdong Provincial People's Hospital were enrolled. Among them, 21 patients were treated with MWA (MWA), 18 with MWA combined with 125I seed implantation (MWA+125I), and 17 with MWA combined with BAI chemotherapy (MWA+BAI). The short-term outcomes, complications, Eastern Cooperative Oncology Group (ECOG) performance score (Zubrod-ECOG-WHO, ZPS), survival, and factors related to survival were compared between the three groups. RESULTS: The response rate of the MWA group (9.52%) was significantly lower than that of the MWA+125I group (50.00%) and MWA+BAI chemotherapy group (47.06%), and the differences were statistically significant (p < 0.05). The incidence of complications in the MWA, MWA+125I, and MWA+BAI chemotherapy groups was 47.62%, 55.56%, and 52.94%, respectively, with no significant difference (p > 0.05). Three months after the treatment, the ZPS of the MWA+125I and MWA+BAI chemotherapy groups was significantly lower than before treatment and significantly lower than that of the MWA group in the same period; the differences were statistically significant (p < 0.05). The median survival time of the MWA+125I group was 18 (9.983, 26.017) months and that of the MWA+BAI chemotherapy group was 21 (0.465, 41.535) months, both of which were higher than that of the MWA group [11 (6.686, 15.314) months]; the differences were statistically significant (p < 0.05). Cox regression analysis was performed on the factors related to survival and revealed treatment mode as a protective factor [HR = 0.433, 95% CI = (0.191, 0.984), p = 0.046]. Other factors, such as gender, age, and tumor size, did not independently affect survival. CONCLUSION: CT-guided MWA combined with 125I seed implantation and MWA combined with BAI chemotherapy are safe and effective for the treatment of advanced lung cancer and metastatic lung cancer, and can control tumor progression and prolong survival time.

Clinical application of optical and electromagnetic navigation system in CT-guided radiofrequency ablation of lung metastases.

PURPOSE: To evaluate the clinical value of CT-guided radiofrequency ablation (RFA) in the diagnosis and treatment of pulmonary metastases under optical and electromagnetic navigation. METHODS: Data on CT-guided radiofrequency ablation treatment of 93 metastatic lung lesions in 70 patients were retrospectively analyzed. There were 46 males and 24 females with a median age of 60.0 years (16-85 years). All lesions were ≤3cm in diameter. 57 patients were treated with 17 G radiofrequency ablation needle puncture directly ablated the lesion without biopsy, and 13 patients were treated with 16 G coaxial needle biopsy followed by radiofrequency ablation. There were 25 cases in the optical navigation group, 25 in the electromagnetic navigation group, and 20 in the non-navigation group. The navigation group was performed by primary interventionalists with less than 5 years of experience, and the non-navigation group was performed by interventionalists with more than 5 years of experience. RESULT: All operations were successfully performed. There was no statistically significant difference in the overall distribution of follow-up results among the optical, electromagnetic, and no navigation groups. Complete ablation was achieved in 84 lesions (90.3%). 7 lesions showed incomplete ablation and were completely inactivated after repeat ablation. 2 lesions progressed locally, and one of them still had an increasing trend after repeat ablation. No serious complications occurred after the operation. CONCLUSIONS: Treatment with optical and electromagnetic navigation systems by less experienced operators has similar outcomes to traditional treatments without navigational systems performed by more experienced operators.

The comparison of pure uterine serous carcinoma and mixed tumor with serous component: a single-institution review of 91 cases.

BACKGROUND: Pure uterine serous carcinoma (p-USC) and mixed tumors with serous component (m-USC) are aggressive subtypes of endometrial cancer associated with high mortality rates. This retrospective study aimed to compare clinicopathologic features and outcomes of p-USC and m-USC in a single center. METHODS: This study retrospectively reviewed patients diagnosed with USC at Peking University People's Hospital between 2008 and 2022. T-tests and chi-square tests were used to compare clinicopathological characteristics between p-USC and m-USC. Kaplan-Meier survival curve and Cox regression analysis were used to analyze the impact of clinical and pathological variables on OS and PFS. RESULTS: Among the 91 patients who underwent surgery, 65.9% (n = 60) were p-USC, and 34.1% (n = 31) were m-USC. Patients with p-USC had earlier menopause (P = 0.0217), a lower rate of progesterone receptor(PR) expression (P < 0.001), and were more likely to have positive peritoneal cytology (P = 0.0464). After a median follow-up time of 40 months, 28 (46.7%) p-USC and 9 (29%) m-USC patients had progression disease, 18 (30%) and 8 (25.8%) patients died of their disease. 5-year PFSR were 51.2% and 75.3%, respectively, and 5-year OS rates were 66% and 67.4%. Kaplan-Meier survival analysis showed that p-USC was more likely to relapse than m-USC (P = 0.034), but there was no significant difference in OS. Cox regression analysis showed that lymph node metastasis and surgical approach were risk factors for OS, and myoinvasion depth ≥ 1/2 was an independent risk factor for PFS. CONCLUSIONS: p-USC was more likely to relapse than m-USC, but there was no significant difference in OS between the two subtypes.

Electrochemical/photoelectrochemical dual-mode aptasensor for sensitive aflatoxin B1 assay based on distance-modulation strategy using Au NPs/PCZIF-8-ZnO as sensing substrate.

Aflatoxin B1 (AFB1), a hepatotoxic and carcinogenic food contaminant, is commonly found in agricultural food. Herein, Au NPs anchored ZIF-8-derived porous carbon-ZnO (Au NPs/PCZIF-8-ZnO) was firstly synthesized to act as the sensing substrate. Then, a ratiometric electrochemical (EC) and "off-on" photoelectrochemical (PEC) dual-mode paper-based aptasensor was presented for AFB1 detection based on a distance-modulation sensing strategy. The independent signal transduction mechanisms and output mode not only broaden the dynamic detection range but also provide a self-verification to assay results, improving the sensitivity and reliability. The wide detection ranges of 0.1 pg/mL-100 ng/mL (EC mode) and 0.02 pg/mL-100 ng/mL (PEC mode) were obtained using dual-mode aptasensor, with detection limits of 36.7 and 9.3 fg/mL, respectively. The fabricated aptasensor exhibited excellent selectivity, reproducibility and stability. Furthermore, it exhibited good practicability for AFB1 assays in real samples, demonstrating great potential applications for food safety evaluation.

Combined Filtering Method for Offshore Oil and Gas Platform Point Cloud Data Based on KNN_PCF and Hy_WHF and Its Application in 3D Reconstruction.

With the increasing scale of deep-sea oil exploration and drilling platforms, the assessment, maintenance, and optimization of marine structures have become crucial. Traditional detection and manual measurement methods are inadequate for meeting these demands, but three-dimensional laser scanning technology offers a promising solution. However, the complexity of the marine environment, including waves and wind, often leads to problematic point cloud data characterized by noise points and redundancy. To address this challenge, this paper proposes a method that combines K-Nearest-Neighborhood filtering with a hyperbolic function-based weighted hybrid filtering. The experimental results demonstrate the exceptional performance of the algorithm in processing point cloud data from offshore oil and gas platforms. The method improves noise point filtering efficiency by approximately 11% and decreases the total error by 0.6 percentage points compared to existing technologies. Not only does this method accurately process anomalies in high-density areas-it also removes noise while preserving important details. Furthermore, the research method presented in this paper is particularly suited for processing large point cloud data in complex marine environments. It enhances data accuracy and optimizes the three-dimensional reconstruction of offshore oil and gas platforms, providing reliable dimensional information for land-based prefabrication of these platforms.

CircSCUBE3 Reduces the Anti-gastric Cancer Activity of Anti-PD-L1.

The progression of gastric cancer (GC) is closely related to tumor immune escape. The research, therefore, studied the impact of possible circRNAs on the immune escape of GC tumors and the underlying mechanisms. Here, to explore circRNAs that may affect GC, the differential circRNAs in six normal gastric mucosal tissues and six GC samples (GSM2005868-GSM2005879) were analyzed through the bioinformatics website circmine, and hsa_circ_0076092 (circSCUBE3) was identified as the research object. In vitro assays revealed the functions of circSCUBE3 and its downstream miRNA/mRNA axis in GC cells. The effect of circSCUBE3 against PD-1 anti-tumor activity was evaluated in vivo. The relationship between circSCUBE3 and miR-744-5p, miR-744-5p, and SLC7A5 was identified by RNA immunoprecipitation and dual-luciferase reporter experiments. The effect of SLC7A5 on GC immune escape by regulating PD-L1 expression was assessed by co-culture system and flow cytometry. CircSCUBE3 was up-regulated in human GC tissues and GC cell lines. circSCUBE3 was associated with poor prognosis in GC patients. Functional experiments reported that circSCUBE3 knockdown could suppress GC immune escape. Mechanistically, circSCUBE3 bound to miR-744-5p, which further targeted SLC7A5, and SLC7A5 can affect GC immune escape by regulating PD-L1. Furthermore, in vivo assay manifested that circSCUBE3 attenuated the anti-tumor effect of PD-L1. Our study revealed the importance of the circSCUBE3/miR-744-5p/SLC7A5 axis in GC immune escape and anti-PD-1 resistance.

The use of Clinicopathological, immunohistochemistry and molecular detection in the diagnosis of fumarate hydratase-deficient uterine leiomyomas.

BACKGROUND: Fumarate hydratase-deficient uterine leiomyomas (FH-dUL) are rare, accounting for only 0.4-1.6% of uterine leiomyomas. FH germline mutation gene is associated with hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCC). METHODS: In this study, we aim to investigate Clinicopathological features and FH mutation in FH-dUL. We performed a retrospective analysis of 300 cases of uterine leiomyoma, diagnosed from January 2017 to December 2021, within the archives of the Department of Pathology at Peking University People's Hospital. In our review of the immunohistochemical(IHC) staining was performed on 300 uSMTs to detect FH deficiency. RESULTS: We identified 21cases (21/300,7%) of FH-dUL. Nineteen cases (6.33%) displayed negative FH. Twenty-one cases (7%) displayed 2SC diffuse plasma and nuclear staining. The most common FH-d morphological features included staghorn vasculature ( 100%,21/21), alveolar-pattern oedema (71.43%, 15/21), scattered bizarre nuclei (23.81%, 5/21), eosinophilic cytoplasmic (rhabdoid) inclusions (47.62%, 10/21), significant eosinophilic nucleolus with peri-nucleolus hollowing (23.81%, 5/21), ovoid nuclei sometimes arranged in chains (9.52%, 2/21). DNA sequencing for the 21 cases was performed using Next Generation Sequencing (NGS). 6 cases were detected significant variations for the FH gene, 11 cases were detected FH gene mutation forvariants of uncertain significance (VUS), and 2 cases were detected a TP53 gene mutation. No related mutations were detected in the other two cases. CONCLUSIONS: FH-dUL is rare. The combination of predictive Clinicopathological evaluation,FH and 2SC IHC test, and molecular test were helpful for the screening of FH-dUL from uSMTs,or even the screening of HLRCC.

Ligation-Based High-Performance Mimetic Enzyme Sensing Platform for Nucleic Acid Detection.

G-quadruplex (G4)/hemin DNAzyme is a promising candidate to substitute horseradish peroxidase in biosensing systems, especially for the detection of nucleic acids. However, the relatively suboptimal catalytic capacity limits its potential applications. This makes it imperative to develop an ideal signal for the construction of highly sensitive biosensing platforms. Herein, we integrated a novel chimeric peptide-DNAzyme (CPDzyme) with the ligase chain reaction (LCR) for the cost-efficient and highly sensitive detection of nucleic acids. By employing microRNA (miRNA) and single-nucleotide polymorphism detection as the model, we designed a G4-forming sequence on the LCR probe with a terminally labeled amino group. Subsequently, asymmetric hemin with carboxylic arms allowed assembly with the LCR products and peptide to form CPDzyme, followed by the magnetic separation of the extraneous components and chemiluminescence detection. Compared with the conventional G4/hemin signaling-based method, the LCR-CPDzyme system demonstrated 3 orders of magnitude improved sensitivity, with accurate quantification of as low as 25 aM miRNA and differentiation of 0.1% of mutant DNA from the pool containing a large amount of wild-type DNA. The proposed LCR-CPDzyme strategy is a potentially powerful method for in vitro diagnostics and serves as a reference for the development of other ligation- or hybridization-based nucleic acid amplification assays.

RNA m6A methylation modulates airway inflammation in allergic asthma via PTX3-dependent macrophage homeostasis.

N6-methyladenosine (m6A), the most prevalent mRNA modification, has an important function in diverse biological processes. However, the involvement of m6A in allergic asthma and macrophage homeostasis remains largely unknown. Here we show that m6A methyltransferases METTL3 is expressed at a low level in monocyte-derived macrophages from childhood allergic asthma patients. Conditional knockout of Mettl3 in myeloid cells enhances Th2 cell response and aggravates allergic airway inflammation by facilitating M2 macrophage activation. Loss and gain functional studies confirm that METTL3 suppresses M2 macrophage activation partly through PI3K/AKT and JAK/STAT6 signaling. Mechanistically, m6A-sequencing shows that loss of METTL3 impairs the m6A-YTHDF3-dependent degradation of PTX3 mRNA, while higher PTX3 expression positively correlates with asthma severity through promoting M2 macrophage activation. Furthermore, the METTL3/YTHDF3-m6A/PTX3 interactions contribute to autophagy maturation in macrophages by modulating STX17 expression. Collectively, this study highlights the function of m6A in regulating macrophage homeostasis and identifies potential targets in controlling allergic asthma.