Genetic and clinical characteristics of genetic tumor syndromes in the central nervous system cancers: Implications for clinical practice.

Recognizing individuals with Genetic tumor syndromes (GTS) in the primary central nervous system (CNS) tumors is crucial for optimizing proper genetic counseling and improving therapeutics and clinical care. We retrospectively analyzed the GTS in a Chinese CNS tumor cohort and examined the molecular characteristics and their clinical significance for diagnostic and therapeutic purposes. Our study identified 34 categories of GTS in 258 patients with CNS tumors. The gene with the highest germline pathogenic or likely pathogenic mutation frequency was TP53, followed by MSH2, NF1, and BRCA2. The top five GTS in CNS tumors showed high genetic heterogeneity GTS analysis reclassifies CNS tumors as "NEC." 53.88% of patients diagnosed with GTS harbor potential precision oncology therapy target mutations. The results of our study deepen our understanding of CNS tumors, provide a reference direction for the future design of clinical trials, and further expect to improve disease entire process management in CNS tumors.

Detection and Anti-Detection with Microwave-Infrared Compatible Camouflage Using Asymmetric Composite Metasurface.

Detection and anti-detection with multispectral camouflage are of pivotal importance, while suffer from significant challenges due to the inherent contradiction between detection and anti-detection and conflict microwave and infrared (IR) stealth mechanisms. Here, a strategy is proposed to asymmetrically control transmitted microwave wavefront under radar-IR bi-stealth scheme using composite metasurface. It is engineered composed of infrared stealth layer (IRSL), microwave absorbing layer (MAL), and asymmetric microwave transmissive structure (AMTS) with polarization conversion from top to bottom. Therein, IR emissivity, microwave reflectivity, and transmissivity are simultaneously modulated by elaborately designing the filling ratio of ITO square patches on IRSL, which ensures both efficient microwave transmission and IR camouflage. Furthermore, full-polarized backward microwave stealth is achieved on MAL by transmitting and absorbing microwaves under x- and y- polarization, respectively, while forward wavefront is controlled by precise curvature phase compensation on AMTS according to ray-tracing technology. For verification, a proof-of-concept metadevice is numerically and experimentally characterized. Both results coincide well, demonstrating spiral detective wavefront manipulation under y-polarized forward wave excitation while effective reduction of radar cross section within 8-18 GHz and low IR emissivity (<0.3) for backward detection. This strategy provides a new paradigm for integration of detection and anti-detection with multispectral camouflage.

Predictive etiological classification of acute ischemic stroke through interpretable machine learning algorithms: a multicenter, prospective cohort study.

BACKGROUND: The prognosis, recurrence rates, and secondary prevention strategies varied significantly among different subtypes of acute ischemic stroke (AIS). Machine learning (ML) techniques can uncover intricate, non-linear relationships within medical data, enabling the identification of factors associated with etiological classification. However, there is currently a lack of research utilizing ML algorithms for predicting AIS etiology. OBJECTIVE: We aimed to use interpretable ML algorithms to develop AIS etiology prediction models, identify critical factors in etiology classification, and enhance existing clinical categorization. METHODS: This study involved patients with the Third China National Stroke Registry (CNSR-III). Nine models, which included Natural Gradient Boosting (NGBoost), Categorical Boosting (CatBoost), Extreme Gradient Boosting (XGBoost), Random Forest (RF), Light Gradient Boosting Machine (LGBM), Gradient Boosting Decision Tree (GBDT), Adaptive Boosting (AdaBoost), Support Vector Machine (SVM), and logistic regression (LR), were employed to predict large artery atherosclerosis (LAA), small vessel occlusion (SVO), and cardioembolism (CE) using an 80:20 randomly split training and test set. We designed an SFS-XGB with 10-fold cross-validation for feature selection. The primary evaluation metrics for the models included the area under the receiver operating characteristic curve (AUC) for discrimination and the Brier score (or calibration plots) for calibration. RESULTS: A total of 5,213 patients were included, comprising 2,471 (47.4%) with LAA, 2,153 (41.3%) with SVO, and 589 (11.3%) with CE. In both LAA and SVO models, the AUC values of the ML models were significantly higher than that of the LR model (P < 0.001). The optimal model for predicting SVO (AUC [RF model] = 0.932) outperformed the optimal LAA model (AUC [NGB model] = 0.917) and the optimal CE model (AUC [LGBM model] = 0.846). Each model displayed relatively satisfactory calibration. Further analysis showed that the optimal CE model could identify potential CE patients in the undetermined etiology (SUE) group, accounting for 1,900 out of 4,156 (45.7%). CONCLUSIONS: The ML algorithm effectively classified patients with LAA, SVO, and CE, demonstrating superior classification performance compared to the LR model. The optimal ML model can identify potential CE patients among SUE patients. These newly identified predictive factors may complement the existing etiological classification system, enabling clinicians to promptly categorize stroke patients' etiology and initiate optimal strategies for secondary prevention.

Solvothermal Preparation of Crystal Seeds and Anisotropy-Controlled Growth of Silver Nanoplates.

We synthesized silver nanoplates using the solvothermal method and, for the first time, placed them as crystal seeds in a water-based growth solution, thereby successfully achieving the large-scale production of silver nanoplates. The synthesis method enabled independent control of the lateral size and vertical size of the silver nanoplates. More specifically, the lateral size could be adjusted within the range of 565 nm-1.682 µm, while the vertical size was achieved by introducing Cl- as a capping agent and the vertical size was thickened from 18.28 to 40.41 nm.

Coastal erosion and flooding risk assessment based on grid scale: A case study of six coastal metropolitan areas.

Coastal areas, situated at the critical juncture of sea-land interaction, are confronted with significant challenges from coastal erosion and flooding. It is imperative to evaluate these risks and offer scientific guidance to foster regional sustainable development. This article developed a coastal risk assessment model based on grid scale, integrating both coastal exposure and socio-ecological environment. Fourteen indicators were selected, aiming to offer a systematic approach for estimating and comparing disaster risks in coastal areas. This risk assessment model was applied to Shanghai, New York, Sydney, San Francisco, Randstad, and Tokyo metropolitan areas. The results indicate: (1) Accounting for the protective role of habitat types like mangroves and the distance attenuation effect offered a more precise representation of hazard situation; (2) The integration of the Game Theory weighting method with both subjective Analytic Hierarchy Process and objective CRITIC weighting enhanced the scientific validity and rationality of the results by minimizing deviations between subjective and objective weights; (3) Shanghai exhibited the highest average hazard and vulnerability, San Francisco had the lowest average hazard and Sydney had the lowest average vulnerability; In terms of comprehensive risk, Shanghai possessed the highest average risk, while Sydney presented the lowest. The proposed model framework is designed to swiftly identify high-risk zones, providing detailed information references for local governments to devise efficacious risk management and prevention strategies.

Bifunctional Chiral Electrocatalysts Enable Enantioselective α-Alkylation of Aldehydes.

Herein, we describe an innovative approach to the asymmetric electrochemical α-alkylation of aldehydes facilitated by a newly designed bifunctional chiral electrocatalyst. The highly efficient bifunctional chiral electrocatalyst combines a chiral aminocatalyst with a redox mediator. It plays a dual role as a redox mediator for electrooxidation, while simultaneously providing remarkable asymmetric induction for the stereoselective α-alkylation of aldehydes. Additionally, this novel catalyst exhibits enhanced catalytic activity and excellent stereoselective control comparable to conventional catalytic systems. As a result, this strategy provides a new avenue for versatile asymmetric electrochemistry. The electrooxidation of diverse phenols enables the C-H/C-H oxidative α-alkylation of aldehydes in a highly chemo- and stereoselective fashion. Detailed mechanistic studies by control experiments and cyclic voltammetry analysis demonstrate possible reaction pathways and the origin of enantio-induction.

Visible Light-Induced Copper-Catalyzed Regio- and Stereoselective Difluoroalkylthiocyanation of Alkynes.

The first regio- and stereoselective difluoroalkylthiocyanation of alkynes with BrCF2R and KSCN has been disclosed under visible light-induced copper catalysis. The copper complex photosensitizer formed in situ not only promotes the generation of CF2-alkyl radicals but also facilitates the construction of C-SCN bonds, allowing the reaction to proceed smoothly without any additional photocatalysts or radical initiators. Moreover, the challenging internal alkynes can also be transformed to deliver CF2-derived tetrasubstituted olefins with potential applications in agricultural and medicinal chemistry.

The clinical efficacy and safety of different biliary drainage in malignant obstructive jaundice: a meta-analysis.

Background: Currently, percutaneous transhepatic cholangial drainage (PTCD) and endoscopic retrograde cholangiopancreatography (ERCP) are commonly employed in clinical practice to alleviate malignant obstructive jaundice (MOJ). Nevertheless, there lacks a consensus regarding the superiority of either method in terms of efficacy and safety. Aim: To conduct a systematic evaluation of the effectiveness and safety of PTCD and ERCP in treating MOJ, and to compare the therapeutic outcomes and safety profiles of these two procedures. Methods: CNKI, VIP, Wanfang, CBM, PubMed, Web of Science, Embase, The Cochrane Library, and other databases were searched for randomized controlled trials (RCTs) on the use of PTCD or ERCP for MOJ. The search period was from the establishment of the databases to July 2023. After quality assessment and data extraction from the included studies, Meta-analysis was performed using RevMan5.3 software. Results: A total of 21 RCTs involving 1,693 patients were included. Meta-analysis revealed that there was no significant difference in the surgical success rate between the two groups for patients with low biliary obstruction (P=0.81). For patients with high biliary obstruction, the surgical success rate of the PTCD group was higher than that of the ERCP group (P < 0.0001), and the overall surgical success rate of the PTCD group was also higher than that of the ERCP group (P = 0.008). For patients with low biliary obstruction, the rate of jaundice relief (P < 0.00001) and the clinical efficacy (P = 0.0005) were better in the ERCP group, while for patients with high biliary obstruction, the rate of jaundice relief (P < 0.00001) and the clinical efficacy (P = 0.003) were better in the PTCD group. There was no significant difference in the overall jaundice remission rate and clinical efficacy between the two groups (P = 0.77, 0.53). There was no significant difference in the reduction of ALT, TBIL, and DBIL before and after surgery and the incidence of postoperative complications between the two groups (P > 0.05). Conclusion: Both PTCD and ERCP can efficiently alleviate biliary obstruction and enhance liver function. ERCP is effective in treating low biliary obstruction, while PTCD is more advantageous in treating high biliary obstruction.

Transcriptomic and Metabolomic Analyses Reveal the Role of Phenylalanine Metabolism in the Maize Response to Stalk Rot Caused by Fusarium proliferatum.

Stalk rot is a prevalent disease of maize (Zea mays L.) that severely affects maize yield and quality worldwide. The ascomycete fungus Fusarium spp. is the most common pathogen of maize stalk rot. At present, the molecular mechanism of Fusarium proliferation during the maize stalk infection that causes maize stalk rot has rarely been reported. In this study, we investigated the response of maize to F. proliferatum infestation by analyzing the phenotypic, transcriptomic, and metabolomic data of inbred lines ZC17 (resistant) and CH72 (susceptible) with different levels of resistance to stalk rot. Physiological and phenotypic results showed that the infection CH72 was significantly more severe than ZC17 after inoculation. Transcriptome analysis showed that after inoculation, the number of differentially expressed genes (DEGs) was higher in CH72 than in ZC17. Nearly half of these DEGs showed the same expression trend in the two inbred lines. Functional annotation and enrichment analyses indicated that the major pathways enriched for DEGs and DEMs included the biosynthesis of plant secondary metabolites, phenylalanine metabolism, biosynthesis of plant hormones, and plant-pathogen interactions. The comprehensive analysis of transcriptome and metabolome data indicated that phenylalanine metabolism and the phenylalanine, tyrosine, and tryptophan biosynthesis pathways played a crucial role in maize resistance to F. proliferatum infection. In addition, a transcription factor (TF) analysis of the DEGs showed that several TF families, including MYB, bHLH, NAC, and WRKY, were significantly activated after inoculation, suggesting that these TFs play important roles in the molecular regulatory network of maize disease resistance. The findings of this study provide valuable insights into the molecular basis of the response of maize to Fusarium proliferatum infection and highlight the importance of combining multiple approaches, such as phenotyping, transcriptomics, and metabolomics, to gain a comprehensive understanding of plant-pathogen interactions.

A recurrence-predictive model based on eight genes and tumor mutational burden/microsatellite instability status in Stage II/III colorectal cancer.

BACKGROUND: Although adjuvant chemotherapy (ACT) is widely used to treat patients with Stage II/III colorectal cancer (CRC), administering ACT to specific patients remains a challenge. The decision to ACT requires an accurate assessment of recurrence risk and absolute treatment benefit. However, the traditional TNM staging system does not accurately assess a patient's individual risk of recurrence. METHODS: To identify recurrence risk-related genetic factors for Stage II/III CRC patients after radical surgery, we conducted an analysis of whole-exome sequencing of 47 patients with Stage II/III CRC who underwent radical surgery at five institutions. Patients were grouped into non-recurrence group (NR, n = 24, recurrence-free survival [RFS] > 5 years) and recurrence group (R, n = 23, RFS <2 years). The TCGA-COAD/READ cohort was employed as the validation dataset. RESULTS: A recurrence-predictive model (G8plus score) based on eight gene (CUL9, PCDHA12, HECTD3, DCX, SMARCA2, FAM193A, AATK, and SORCS2) mutations and tumor mutation burden/microsatellite instability (TMB/MSI) status was constructed, with 97.87% accuracy in our data and 100% negative predictive value in the TCGA-COAD/READ cohort. For the TCGA-COAD/READ cohort, the G8plus-high group had better RFS (HR = 0.22, p = 0.024); the G8plus-high tumors had significantly more infiltrated immune cell types, higher tertiary lymphoid structure signature scores, and higher immunological signature scores. The G8plus score was also a predict biomarker for immunotherapeutic in advanced CRC in the PUCH cohort. CONCLUSIONS: In conclusion, the G8plus score is a powerful biomarker for predicting the risk of recurrence in patients with stage II/III CRC. It can be used to stratify patients who benefit from ACT and immunotherapy.

Effects of microcystin on protein profile in hepatopancreas of Litopenaeus vannamei.

For intensive aquaculture in freshwater ponds, microcystin (MC-LR) generated from cyanobacterial blooms is one of the bottlenecks for the healthy and sustainable development of shrimp aquaculture industry. In this study, we measured the MC-LR content in the hepatopancreas and muscles of Litopenaeus vannamei stressed by MC-LR, and analyzed protein expression in the hepatopancreas using DIA high-throughput proteomics technology. The results showed that MC-LR content in the hepatopancreas and muscles reached the highest at 1 h after MC-LR injection, which was (6.12±0.45) µg·kg-1 and (5.00±0.19) µg·kg-1, respectively. Then, it decreased gra-dually, with that in the hepatopancreas being significantly higher than in muscles. We identified 820 differential expressed proteins, including 586 up-regulated and 234 down-regulated ones. Results of bioinformatics analysis showed that MC-LR stress significantly affected immune-related pathways such as lysosome, RIG-Ⅰ receptor signals and interleukin-2. It also altered energy metabolisms including citrate cycle, metabolism of starch and sucrose, and interconversion of pentose and glucoronate, which in turn led to the disorder of carbohydrate metabolism. In addition, MC-LR significantly upregulated 19 cytoskeleton-related blood shadow proteins and damaged the hepatopancreas cytoskeleton. It was concluded that MC-LR mainly affected the physiological processes associated with immunity, energy metabolism, and cytoskeleton in the hepatopancreas of L. vannamei.

Perineal defect reconstruction after surgery for advanced or locally recurrent rectal cancer involving organ resection: Multiple flaps combined with lining repair.

AIM: The aim of this study was to investigate the efficacy of multiple perineal perforator flaps in repairing deep perineal defects after pelvic exenteration for locally advanced or recurrent rectal cancer. METHOD: We investigated the outcomes of eight patients whose repairs involved a novel method of using an internal pudendal artery perforator (IPAP) flap combined with an inferior gluteal artery perforator (IGAP) flap. RESULTS: There were four male and four female patients with a mean age of 56 years (36-72 years). Bilateral IPAP flaps combined with bilateral IGAP flaps were used in five patients, unilateral IPAP flaps combined with bilateral IGAP flaps were used in two patients and bilateral IPAP flaps were used in one patient. There were no functional limitations in daily activities during the 6-month follow-up period. CONCLUSION: Our study showed that using multiple perineal perforator flaps combined with lining repair is feasible for repairing deep perineal defects in patients who have undergone rectal cancer surgery that includes pelvic exenteration.

E2F3 accelerates the stemness of colon cancer cells by activating the STAT3 pathway.

Introduction: Colon cancer is one of the most prevalent malignancies and causes of cancer-related deaths worldwide. Thus, further research is required to explicate the latent molecular mechanisms and look for novel biomarkers. E2F3 has been confirmed to be an oncogene in a variety of cancers. However, the particular regulation of E2F3 in colon cancer needs further investigation. Methods: The self-renewal ability was detected through a sphere formation assay. The tumorigenic ability was measured through nude mice in vivo assay. The protein expression of genes was examined through a Western blot. The expression of E2F3 in tumor tissues was detected through an IHC assay. The resistance to cisplatin was assessed through the CCK-8 assay. The cell migration and invasion abilities were measured after upregulating or suppressing E2F3 through the Transwell assay. Results: Results uncovered that E2F3 was upregulated in spheroid cells. In addition, E2F3 facilitates stemness in colon cancer. Moreover, E2F3 facilitated colon cancer cell migration and invasion. Finally, it was revealed that E2F3 affected the STAT3 pathway to modulate stemness in colon cancer. E2F3 served as a promoter regulator in colon cancer, aggravating tumorigenesis and stemness in colon cancer progression through the STAT3 pathway. Conclusion: E2F3 may be a useful biomarker for anticancer treatment in colon cancer.

Visible-Light-Induced Copper-Catalyzed Intermolecular Three-Component Difluoroalkyl Thiocyanidation of Alkenes.

In this report, we develop a new strategy for visible-light-induced, copper-catalyzed three-component difluoroalkyl thiocyanidation of alkenes to construct a series of important difluorothiocyanate compounds. The new approach can also be applied to perfluorothiocyanate compounds, even target molecules containing drug/natural product skeletons. Mechanistic studies provide that the copper complex plays a dual role, as both the photoredox catalyst for electron transfer and the cross-coupling catalyst for C-SCN bond formation.

Rectal cancer-derived exosomes activate the nuclear factor kappa B pathway and lung fibroblasts by delivering integrin beta-1.

Numerous studies have revealed the importance of tumor-derived exosomes in rectal cancer (RC). This study aims to explore the influence of tumor-derived exosomal integrin beta-1 (ITGB1) on lung fibroblasts in RC along with underlying mechanisms. Exosome morphology was observed using a transmission electron microscope. Protein levels of CD63, CD9, ITGB1, p-p65 and p65 were detected using Western blot. To determine ITGB1's mRNA expression, quantitative real-time polymerase chain reaction was used. Moreover, levels of interleukin (IL)-8, IL-1ß, and IL-6 in cell culture supernatant were measured via commercial ELISA kits. ITGB1 expression was increased in exosomes from RC cells. The ratio of p-p65/p65 as well as levels of interleukins in lung fibroblasts was raised by exosomes derived from RC cells, while was reduced after down-regulation of exosomal ITGB1. The increased ratio of p-p65/p65 as well as levels of pro-inflammatory cytokines caused by exosomes from RC cells was reversed by the addition of nuclear factor kappa B (NF-κB) inhibitor. We concluded that the knockdown of RC cells-derived exosomal ITGB1 repressed activation of lung fibroblasts and the NF-κB pathway in vitro.

Breviscapine regulates the proliferation, migration, invasion, and apoptosis of colorectal cancer cells via the PI3K/AKT pathway.

Colorectal cancer (CRC) is ranked as one of the most common malignancies with a high death rate. It has been discovered that breviscapine can alter the progression and development of various cancers. Nevertheless, the function and mechanisms of breviscapine in CRC progression have not yet been described. The cell proliferation capacity of HCT116 and SW480 cells was assessed using the CCK-8 and EdU assays. Cell apoptosis was tested through flow cytometry, and cell migration and invasion were examined using the transwell assay. Moreover, protein expression was examined through a western blot. Tumor weight and volume were assessed using the nude mice in vivo assay, and the Ki-67 protein expression was verified through the IHC assay. This study discovered that an increased dose of breviscapine (0, 12.5, 25, 50, 100, 200, and 400 µM) gradually reduced cell proliferation and increased apoptosis in CRC. Additionally, breviscapine restricted the migration and invasion CRC cells. Moreover, it was revealed that breviscapine inactivated the PI3K/AKT pathway and inhibited CRC progression. Finally, an in vivo assay demonstrated that breviscapine restrained tumor growth in vivo. It affected the CRC cells' proliferation, migration, invasion, and apoptosis through the PI3K/AKT pathway. This discovery may offer new insights into CRC treatment.

Copper-catalyzed radical-mediated intermolecular cyanomonofluoroalkylation of alkenes and alkynes.

A novel copper-catalyzed three-component reaction of monofluoroalkylation agents, alkenes and TMSCN is described. In addition, alkynes could also be compatible with the reaction system to obtain three-component products for the first time with moderate yield and excellent E/Z stereoselectivity. This reaction provides a facile method for the synthesis of cyanomonofluoroalkyl compounds, which may serve as potentially useful organic intermediates for further transformations. Preliminary mechanistic investigation indicated that monofluoroalkyl free radicals were involved in the cyanomonofluoroalkylation process.