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INTRODUCTION: Plant bacterial diseases take an incalculable toll on global food security. The indiscriminate use of chemical synthetic pesticide not only facilitates pathogen resistance of pathogenic bacteria, but also poses a major threat to human health and environmental protection. Therefore, it is of great economic value and scientific significance to develop a new antibacterial drug with environmental friendliness and unique mechanism of action. OBJECTIVES: To design and synthesize formononetin derivatives based on natural products, evaluate their in vitro and in vivo antibacterial activities and elucidate the mechanisms involved. METHODS: The synthesis was carried out by classical active group splicing method. The antibacterial activities were evaluated using turbidimetry and pot experiments. The antibacterial mechanism was further investigated using scanning electron microscopy (SEM), virulence factors, defense enzymes activities, proteomics and metabolomics. RESULTS: 40 formononetin derivatives containing benzyl piperidine were designed and synthesized. The antibacterial results demonstrated that H32 exhibited the most potent inhibitory effect against Xanthomonas oryzae pv. Oryzae (Xoo) with the EC50 of 0.07 µg/mL, while H6 displayed the highest inhibitory activity against Xanthomonas axonopodis pv. Citri (Xac) with the EC50 of 0.24 µg/mL. Furthermore, the control efficacy of H32 against rice bacterial leaf blight (BLB) and H6 against citrus canker (CC) was validated through pot experiments. SEM, virulence factors and host enzyme activities assay indicated that H32 could not only reduce the virulence of Xoo, but also activate the activities of defense enzymes and improve the disease resistance of host plants. The proteomics and metabolomics analysis demonstrated that H32 could inhibit the synthesis of branched-chain amino acids, make Xoo cells in a starvation state, inhibit its proliferation, weaken its virulence and reduce its colonization and infection of host cells. CONCLUSION: Formononetin derivatives containing benzyl piperidine could be used as potentially effective inhibitors against Xanthomonas spp.

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Prostate cancer (PCa) exhibits significant geoethnic disparities as reflected by distinct variations in the cancer genome and disease progression. Here, we perform a comprehensive proteogenomic characterization of localized high-risk PCa utilizing paired tumors and nearby tissues from 125 Chinese male patients, with the primary objectives of identifying potential biomarkers, unraveling critical oncogenic events and delineating molecular subtypes with poor prognosis. Our integrated analysis highlights the utility of GOLM1 as a noninvasive serum biomarker. Phosphoproteomics analysis reveals the crucial role of Ser331 phosphorylation on FOXA1 in regulating FOXA1-AR-dependent cistrome. Notably, our proteomic profiling identifies three distinct subtypes, with metabolic immune-desert tumors (S-III) emerging as a particularly aggressive subtype linked to poor prognosis and BCAT2 catabolism-driven PCa progression. In summary, our study provides a comprehensive resource detailing the unique proteomic and phosphoproteomic characteristics of PCa molecular pathogenesis and offering valuable insights for the development of diagnostic and therapeutic strategies.

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OBJECTIVE: Five cases of giant cell tumor of bone (GCTB) in the head and neck region were reported, with a main focus on the radiological findings to identify common characteristics for the diagnosis of GCTB in these sites. MATERIALS AND METHODS: Five consecutive patients diagnosed with GCTB were retrospectively selected. Radiological features on conventional and advanced MR sequences and CT were analyzed. HE staining and immunohistochemical examination were performed using antibodies against p63 and CD68. RESULTS: The common clinical features were local mass (3/5), tinnitus (3/5) and headache (2/5). Radiologically, all the cases were well-circumscribed osteolytic lesion, majority of cases demonstrated an expansile growth pattern and "soap bubble" appearance on CT (4/5). On MRI, the tumors showed predominantly hypointensity both on T1WI and T2WI, and no evidence of restricted diffusion on DWI. Intratumoral hemorrhage (2/5), cystic alternation (2/5) and very low signal on T2WI in the periphery region of the tumor (4/5) was found. Fluid-fluid level was noted in one case, which was eventually verified to be GCTB with secondary aneurysmal bone cyst (ABC). With contrast agent, all the cases showed striking (3/5) or mild to intermediate (2/5) enhancement. CONCLUSIONS: Although the above described radiological findings are not specific for GCTB in head and neck region, a well-defined osteolytic lesion in the bones of head and neck region with "soap bubble" appearance on CT and hypointensity on T2WI with very low signal in the peripheral region of the tumor on MRI highly suggest GCTB for patient ages 20 to 40.

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PURPOSE: To describe clinical features, risk factors, and outcomes of patients with perineal and perianal rhabdomyosarcoma. METHODS: The records of 51 patients (38 perineal and 13 perianal) enrolled on Children's Oncology Group clinical trials between 1997 and 2012 were reviewed. RESULTS: At presentation, 53% were female, 65% were older than 10 years of age, 76% were alveolar histology, 76% were more than 5 cm, 84% were invasive, 65% were regional node positive by imaging, 49% were metastatic, only 16% were grossly resected upfront, and 25% of patients had a delayed excision. At a median follow-up of 6.13 years, estimated 5-year event-free survival (EFS) was 38% [22.17%-53.38%], and overall survival (OS) was 42% [26.66%-58.21%]. The rates of local, regional, and distant failure were 15.6%, 13.7%, 43.1%, respectively; all failures ultimately died. By univariate analysis, only age more than 10 years negatively impacted 5-year EFS (p = .023) and OS (p = .09), and IRS Group also impacted OS (p = .043). In Cox proportional hazards model, neither of these variables were significant after adjusting for other factors. CONCLUSION: Patients with perineal and perianal rhabdomyosarcoma have a poor overall prognosis, probably related to poor patient and disease characteristics at presentation.

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A series of flavonol derivatives containing piperazine and quinoxaline had been designed and synthesized. The biological activity test results showed that some of the target compounds had good antifungal activity against various fungi. N5 had the best antifungal activity against Phomopsis sp (P.s.) and Phytophthora capsica (P.c.). The half maximal effective concentration (EC50) was 12.9 and 25.8 µg/mL against P.s. and P.c., respectively, which were better than azoxystrobin (Az, 25.4 and 71.1 µg/mL). In addition, the protective and curative activities of N5 against kiwifruit were 85.9 and 67.0% at 200 µg/mL in vivo, which were better than that of Az (65.9 and 57.0%). The protective and curative activities against chili leaves were 80.6 and 66.5% at 200 µg/mL, which were better than that of Az (77.6 and 60.0%). The scanning electron microscopy (SEM) experiment showed that the action of N5 caused the mycelium to bend and fold, changed its morphology and caused damaged to the mycelium. Through the measurement of relative conductivity, leakage of cytoplasmic contents and determination of malondialdehyde (MDA) content indicated that N5 could damage the integrity of pathogenic fungal cell membranes, change the permeability of cell membranes, and affect the normal growth of mycelium.

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OBJECTIVES: To assess the efficacy and safety of preoperative neoadjuvant everolimus in renal angiomyolipomas (AML) patients with or without Tuberous Sclerosis Complex (TSC). MATERIALS AND METHODS: This multi-institutional retrospective study enrolled renal AML patients who underwent partial nephrectomy (PN) or total nephrectomy after receiving at least 1 month of pre-operative everolimus. Imaging evaluations were collected before and after treatment, along with demographic, surgical, and follow-up information. The primary outcome was tumor volume reduction of ≥25%, with additional outcomes including recurrence, perioperative outcomes, renal function, and safety. RESULTS: From January 2015 to July 2022, 68 renal AML patients were studied-41 with TSC and 27 without. During everolimus treatment, 61.0% (25/41) of TSC patients and 44.4% (12/27) of non-TSC patients achieved tumor reduction of ≥25%. Additionally, 41.5% (17/41) of TSC patients and 18.5% (5/27) of non-TSC patients achieved a ≥ 50% reduction. Three TSC patients and 1 non-TSC patient discontinued treatment due to side-effects. Most patients (92.7% TSC, 85.2% non-TSC) underwent PN. After everolimus treatment, the necessary total nephrectomy decreased to 41.2% (7/17) from baseline. Postoperatively, 1 grade 3 and 3 grade 2 complications occurred, with no grade 4 or 5 complications. After a median follow-up of 24 months, only 1 TSC patient recurred with a diameter >3 cm. Retrospective nature is the major limitation of this study. CONCLUSION: Everolimus was effective and well-tolerated in neoadjuvant treatment for renal AML, especially in TSC patients. This neoadjuvant combination strategy of everolimus and PN could effectively controls recurrence and preserves renal function.

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Targeted delivery systems combined with the stimuli-responsive release of drug molecules hold noteworthy promise for precision medicine, enabling treatments with enhanced effectiveness and reduced adverse effects. An ideal drug delivery platform with versatile targeting moieties, the capability of combinational payloads, and simple preparation is highly desirable. Herein, we developed pH-sensitive fluorescent self-assembled complexes (SACs) of a galactose-functionalized G-quadruplex (G4) and a coumarin carboxamidine derivative as a targeted delivery platform through the nanoprecipitation method. These SACs selectively targeted hepatocellular carcinoma (HepG2) cells in fluorescence imaging after a short incubation and exerted specific anticancer effects in an appropriate dose range. Co-delivery of 1 µM prodrug floxuridine oligomers and 16 µg/mL SACs (minimal hemolytic effect) significantly reduced the cytotoxicity of the nucleoside anticancer drug on normal cells (NIH/3T3), kept up to 70% alive after 72-h incubation, and improved anticancer efficacy compared to SACs alone. This strategy can be extended to ratiometric multidrug delivery through self-assembly for targeted combinational therapy.

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PURPOSE: Patients with rhabdomyosarcoma with metastatic disease have a poor prognosis despite therapy intensification. The aim of this study was to investigate the efficacy of whole lung irradiation (WLI) in patients with rhabdomyosarcoma and lung metastases. METHODS: Patients with rhabdomyosarcoma with lung metastases enrolled on four Children's Oncology Group protocols (D9802, D9803, ARST08P1, ARST0431) were retrospectively reviewed. Event-free survival (EFS) and overall survival (OS) were compared between patients who received and did not receive WLI. RESULTS: In 143 patients with rhabdomyosarcoma with lung metastases, 65 patients (45.5%) received WLI and 78 patients (54.5%) did not receive WLI despite protocol requirements. The 5-year EFS was 38.3% (95% CI, 24.8 to 51.8) in patients who received WLI and 25.2% (95% CI, 13.8 to 36.6) in patients who did not receive WLI (P = .0496). The 5-year OS was 45.5% (95% CI, 31.8 to 59.3) in patients who received WLI and 32.4% (95% CI, 20.4 to 44.4) in patients who did not receive WLI (P = .08). In exploratory subgroup analyses, the benefit of WLI on EFS and OS was significant in patients 10 years and older. Other clinical factors associated with EFS on univariable analysis included age, histology FOXO1 fusion status, number of metastatic sites, location of metastatic sites, and Oberlin Score. CONCLUSION: WLI is associated with improved EFS in patients with rhabdomyosarcoma with lung metastases. These results highlight the potential importance of WLI and need for more stringent protocol compliance for administering WLI.

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Microplastics are heterogeneously distributed in soils. However, it is unknown whether soil microplastic heterogeneity affects plant growth and root foraging responses and whether such effects vary with plant species and microplastic types. We grew each of seven herbaceous species (Platycodon grandiflorus, Trifolium repens, Portulaca oleracea, Medicago sativa, Taraxacum mongolicum, Perilla frutescenst, and Paspalum notatum) in heterogeneous soil (patches without microplastics and patches with 0.2 % microplastics) and homogeneous soil (patches with 0.1 % microplastics). Three microplastic types were tested: polypropylene (PP), polyacrylonitrile (PAN), and polyester (PET). P. frutescens showed no response to soil microplastic heterogeneity. For P. grandiflora, microplastic heterogeneity tended to decrease its biomass (total, shoot and root) when the microplastic was PAN and also shoot biomass when it was PET, but had no effect when it was PP. For T. repens, microplastic heterogeneity promoted biomass when PAN was used, decreased total and root biomass when PET was used, but showed no effect when PP was used. Microplastic heterogeneity increased biomass of P. oleracea and decreased that of M. sativa when PET was used, but had no effect when PP or PAN was used. For T. mongolicum, microplastic heterogeneity reduced biomass when the microplastic was PAN, tended to increase total and root biomass when it was PP, but showed no effect when it was PET. For P. notatum, microplastic heterogeneity increased biomass when the microplastic was PP, decreased it when PET was used, but had no effect when PAN was used. However, biomass of none of the seven species showed root foraging responses at the patch level. Therefore, soil microplastic heterogeneity can influence plant growth, but such effects depend on species and microplastic types and are not associated with root foraging. Our findings highlight the roles of soil microplastic heterogeneity, which may influence species interactions and community structure and productivity.

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Curcumin, extracted from Zingiberaceae and Araceae rhizomes, is clinically used for its anti-inflammatory, antibacterial, antioxidant, and anti-cancer properties. Its safety and potential make it a promising base for designing enhanced derivatives. The focus now is on optimizing curcumin and synthesizing more potent 1,4-pentadien-3-ones, which have anti-cancer activities. In the realm of triple-negative breast cancer (TNBC), an aggressive and invasive form with high metastatic potential, the need for innovative treatments is acute. The challenges posed by chemotherapy resistance, recurrence, and TNBC's heterogeneity have emphasized the necessity for novel therapeutic approaches. Our strategy involved the integration of a quinoxaline ring into 1,4-pentadien-3-one, followed by subsequent modifications. In this study, N17 demonstrated the ability to induce cell death and effectively suppress cell proliferation in breast cancer cells. These observed anti-cancer effects were attributed to the inhibition of p-AKT(S473), a key regulator implicated in both cell apoptosis and the modulation of epithelial-mesenchymal transition process in breast cancer cells. Furthermore, our investigation indicated N17 achieves its inhibitory effects on p-AKT(S473) by specifically targeting the CSNK1G3 protein. Remarkably, N17 not only impedes the EMT process but also triggers apoptosis through the CSNK1G3/AKT signaling axis. These findings provide the critical role of CSNK1G3 as an anti-cancer regulator in TNBC, establishing N17 as a pharmacological intervention with immense promise for treating cancer metastasis.

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Cancer immunotherapy has emerged as a promising approach to cancer treatment in recent years. The physical and chemical properties of nanocarriers are critical factors that regulate the immune activation of antigen-presenting cells (APCs) in the tumor microenvironment (TME). Herein, we extensively investigated the behavior of liposome nanoparticles (Lipo-NPs) with different elasticities, focusing on their interaction with immune cells and their transport mechanisms from tumors to tumor-draining lymph nodes (tdLNs). Successfully preparing Lipo-NPs with distinct elastic properties, their varied behaviors were observed, concerning immune cell interaction. Soft Lipo-NPs exhibited an affinity to cell membranes, while those with medium elasticity facilitated the cargo delivery to macrophages through membrane fusion. Conversely, hard Lipo-NPs enter macrophages via classical cellular uptake pathways. Additionally, it was noted that softer Lipo-NPs displayed superior transport to tdLNs in vivo, attributed to their deformable nature with lower elasticity. As a result, the medium elastic Lipo-NPs with agonists (cGAMP), by activating the STING pathway and enhancing transport to tdLNs, promoted abundant infiltration of tumor-infiltrating lymphocytes (TILs), leading to notable antitumor effects and extended survival in a melanoma mouse model. Furthermore, this study highlighted the potential synergistic effect of medium elasticity Lipo-NPs with immune checkpoint blockade (ICB) therapy in preventing tumor immune evasion. These findings hold promise for guiding immune-targeted delivery systems in cancer immunotherapy, particularly in vaccine design for tdLNs targeting and eradicating metastasis within tdLNs.

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Tumor cell-derived extracellular vesicles (TEVs) contain numerous cellular molecules and are considered potential biomarkers for non-invasive liquid biopsy. However, due to the low abundance of TEVs secreted by tumor cells and their phenotypic heterogeneity, there is a lack of sensitive and specific methods to quantify TEVs. Here, we developed a dual-aptamer proximity ligation-coupled hybridization chain reaction (HCR) method for tracing TEVs, exploiting CRISPR to achieve highly sensitive detection. Taking advantage of the high binding affinity of aptamers, the two aptamers (AptEpCAM, AptHER2) exhibited the high selectivity for TEVs recognition. HCR generated long-repeated sequence containing multiple crRNA targetable barcodes, and the signals were further amplified by CRISPR upon recognizing the HCR sequences, thereby enhancing the sensitivity. Under optimal conditions, the developed method demonstrated a favorable linear relationship in the range of 2 × 103-107 particles/µL, with a limit of detection (LOD) of 3.3 × 102 particles/µL. We directly applied our assay to clinical plasma analysis, achieving 100 % accuracy in cancer diagnosis, thus demonstrating the potential clinical applications of TEVs. Due to its simplicity and rapidity, excellent sensitivity and specificity, this method has broad applications in clinical medicine.

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OBJECTIVE: This study employed a randomized controlled trial to assess the efficacy of virtual-reality (VR) simulators and physical model simulators on colonoscopy training to explore the optimal and evidence-based simulation training. DESIGN: Forty participants were divided into 2 groups and randomized as dyads: the VR simulator group and the physical model simulator group. All the participants performed a baseline test through porcine colonoscopy. After a 6 h simulation training, each participant underwent a post-test on a pig after bowel preparation, and the procedures were video-recorded. Both the baseline test and the post-test were blindly assessed by 2 experienced assistant director physicians based on the GAGES-C scoring system. SETTING: Simulation center, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai. PARTICIPANTS: Forty surgical residents without colonoscopy experience. RESULTS: Both the VR simulator group and the physical model simulator group improved significantly over the baseline test. The VR simulator group performed significantly better than the physical model simulator group, p=0.042. The participants in both groups expressed a high level of simulator satisfaction. CONCLUSIONS: Novice residents can benefit from both VR simulators and physical model simulators. The VR simulator was shown to be more effective for colonoscopy training. VR simulators were more recommended for novices conducting basic colonoscopy training.

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Uracil-DNA glycosylase (UDG), an enzyme for repairing uracil-containing DNA damage, is crucial for maintaining genomic stability. Simple and fast quantification of UDG activity is essential for biological assay and clinical diagnosis, since its aberrant level is associated with DNA damage and various diseases. Herein, we developed a fully integrated "sample in-signal out" distance-based paper analytical device (dPAD) for visual quantification of UDG using a flow-controlled uracil-rich DNA hydrogel (URDH). The uracil base sites contained in the DNA hydrogel are mis-incorporated with dUTP by rolling circle amplification (RCA), which simplifies the preparation process of the functionalized hydrogel. In the presence of UDG, the uracil in URDH can be recognized and removed to induce the permeability change of URDH, resulting in the visible distance signal along the paper channel. Using dPAD, as low as 6.4 × 10-4 U/mL of UDG (within 80 min) is visually identified without any instruments and complicated operations. This integrated dPAD is advantageous for its simplicity, cost effectiveness, and ease of use. We envision that it has the great potential for point-of-care testing (POCT) in DNA damage testing, personalized healthcare assessment, and biomedical applications.

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Abrocitinib is a selective Janus kinase 1 inhibitor approved for the treatment of atopic dermatitis. It is metabolized primarily by cytochrome P450 (CYP) 2C19 (approximately 53%) and CYP2C9 (approximately 30%), which form 2 active metabolites. The pharmacologic activity of abrocitinib is attributable to the unbound exposures of abrocitinib and those metabolites with active moiety area under the plasma concentration-time curve (AUC) considered the best measure of the total pharmacological effect. The effect of CYP2C19 and/or CYP2C9 genotypes on abrocitinib and active moiety exposures were evaluated using a meta-analysis of the noncompartmental estimates of exposure pooled from 10 clinical studies. A linear mixed-effects model was developed on the basis of the power model to evaluate the effect of CYP2C19 and/or CYP2C9 genotypes on exposure (i.e., abrocitinib AUC and peak plasma concentration, active moiety AUC and peak plasma concentration). The genotypes were evaluated individually and as a combined phenotype effect. When evaluating the poor metabolizers of CYP2C19 or CYP2C9 individually, the estimated increases were 44.9% and 42.0% in active moiety AUC, respectively. The combined phenotype models showed a 0.6% decrease, and 25.1% and 10.5% increases in the active moiety AUC for "elevated," "mixed," and "reduced" metabolizers, respectively. Overall, the active moiety exposures did not appear to be affected to a clinically meaningful extent by different genotypes of CYP2C19 and/or CYP2C9.

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Introduction: The infertile patient's knowledge, attitude, and practice (KAP) toward embryo transfer may affect treatment outcomes and the mental health of women who underwent in vitro fertilization-embryo transfer (IVF-ET). This study aimed to investigate the KAP of embryo transfer among women who underwent IVF-ET. Methods: This cross-sectional study was conducted on women who underwent IVF-ET at our Hospital between May 2023 and November 2023, using a self-designed questionnaire. Results: A total of 614 valid questionnaires were finally included. The mean KAP scores were 19.46 ± 5.06 (possible range: 0 28), 39.41 ± 5.20 (possible range: 12-60), and 48.02 ± 6.75 (possible range: 0-60), respectively. The structural equation model demonstrated that knowledge has a direct effect on attitude (ß = 0.27, p < 0.001) and attitude has a direct effect on practice (ß = 0.55, p < 0.001) and anxiety (ß = 0.59, p < 0.001). Moreover, multivariable linear regression analysis showed that anxiety score [coefficient = 0.09, 95% confidence interval (CI): 0.03-0.16, p = 0.003], BMI (coefficient = 0.09, 95%CI: 0.03-0.16, p = 0.003), education (coefficient = 5.65-6.17, 95%CI: 1.09-10.7, p < 0.05), monthly per capita income (coefficient = 1.20-1.96, 95% CI: 0.21-3.07, p = 0.05), reasons for IVF (coefficient = -1.33-1.19, 95% CI: -2.49-0.09, p < 0.05), and more than 5 years of infertility (coefficient = -1.12, 95% CI: -2.11-0.13, p = 0.026) were independently associated with sufficient knowledge. Knowledge (coefficient = 0.19, 95% CI: 0.12-0.26, p < 0.001), anxiety (coefficient = 0.39, 95% CI: 0.34-0.45, p < 0.001), monthly per capita household income >10,000 (coefficient = 1.52, 95% CI: 0.61-2.43, p < 0.001), and three or more cycles of embryo transfer (coefficient = -2.69, 95% CI: -3.94-1.43, p < 0.001) were independently associated with active attitude. Furthermore, attitude (coefficient = 0.21, 95% CI: 0.11-0.30, p < 0.001) and anxiety (coefficient = 0.57, 95% CI: 0.49-0.65, p < 0.001) were independently associated with proactive practice. Discussion: Women who underwent IVF-ET had inadequate knowledge and negative attitudes but proactive practice toward embryo transfer, which were affected by anxiety, income, and reasons for IVF. It is necessary to strengthen the continuous improvement of patient education to improve the management of embryo transfer.

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Cucumber is an important vegetable crop that has high nutritional and economic value and is thus favored by consumers worldwide. Exploring an accurate and fast technique for measuring the morphological traits of cucumber fruit could be helpful for improving its breeding efficiency and further refining the development models for pepo fruits. At present, several sets of measurement schemes and standards have been proposed and applied for the characterization of cucumber fruits; however, these manual methods are time-consuming and inefficient. Therefore, in this paper, we propose a cucumber fruit morphological trait identification framework and software called CucumberAI, which combines image processing techniques with deep learning models to efficiently identify up to 51 cucumber features, including 32 newly defined parameters. The proposed tool introduces an algorithm for performing cucumber contour extraction and fruit segmentation based on image processing techniques. The identification framework comprises 6 deep learning models that combine fruit feature recognition rules with MobileNetV2 to construct a decision tree for fruit shape recognition. Additionally, the framework employs U-Net segmentation models for fruit stripe and endocarp segmentation, a MobileNetV2 model for carpel classification, a ResNet50 model for stripe classification and a YOLOv5 model for tumor identification. The relationships between the image-based manual and algorithmic traits are highly correlated, and validation tests were conducted to perform correlation analyses of fruit surface smoothness and roughness, and a fruit appearance cluster analysis was also performed. In brief, CucumberAI offers an efficient approach for extracting and analyzing cucumber phenotypes and provides valuable information for future cucumber genetic improvements.

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Due to the absence of a gold standard for threshold selection, brain networks constructed with inappropriate thresholds risk topological degradation or contain noise connections. Therefore, graph neural networks (GNNs) exhibit weak robustness and overfitting problems when identifying brain networks. Furthermore, existing studies have predominantly focused on strongly coupled connections, neglecting substantial evidence from other intricate systems that highlight the value of weakly coupled connections. Consequently, the potential of weakly coupled brain networks remains untapped. In this study, we pioneeringly construct weakly coupled brain networks and validate their values in emotion identification tasks. Subsequently, we propose a sparse adaptive gated GNN (SAGN) that can simultaneously perceive the valuable topology of dual-view (i.e., strongly coupled and weakly coupled) brain networks. The SAGN contains a sparse adaptive global receptive field. Moreover, SAGN employs a gated mechanism with feature enhancement and adaptive noise suppression capabilities. To address the lack of inductive bias and the large capacity of SAGN, a graph regularization term built with prior topology of dual-view brain networks is introduced to enhance generalization. Besides a public dataset (SEED), we also built a custom dataset (MuSer) with 60 subjects to evaluate weakly coupled brain networks' value and validate the SAGN's performance. Experiments demonstrate that brain physiological patterns associated with different emotional states are separable and rooted in weakly coupled brain networks. In addition, SAGN exhibits excellent generalization and robustness in identifying brain networks.

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The capsular polysaccharide (CPS) is a major virulence factor of the pathogenic Acinetobacter baumannii and a promising target for vaccine development. However, the synthesis of the 1,2-cis-2-amino-2-deoxyglycoside core of CPS remains challenging to date. Here we develop a highly α-selective ZnI2-mediated 1,2-cis 2-azido-2-deoxy chemical glycosylation strategy using 2-azido-2-deoxy glucosyl donors equipped with various 4,6-O-tethered groups. Among them the tetraisopropyldisiloxane (TIPDS)-protected 2-azido-2-deoxy-d-glucosyl donor afforded predominantly α-glycoside (α : ß = >20 : 1) in maximum yield. This novel approach applies to a wide acceptor substrate scope, including various aliphatic alcohols, sugar alcohols, and natural products. We demonstrated the versatility and effectiveness of this strategy by the synthesis of A. baumannii K48 capsular pentasaccharide repeating fragments, employing the developed reaction as the key step for constructing the 1,2-cis 2-azido-2-deoxy glycosidic linkage. The reaction mechanism was explored with combined experimental variable-temperature NMR (VT-NMR) studies and mass spectroscopy (MS) analysis, and theoretical density functional theory calculations, which suggested the formation of covalent α-C1GlcN-iodide intermediate in equilibrium with separated oxocarbenium-counter ion pair, followed by an SN1-like α-nucleophilic attack most likely from separated ion pairs by the ZnI2-activated acceptor complex under the influence of the 2-azido gauche effect.

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BACKGROUND: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Despite bone metastases being present in 5% of patients at diagnosis, there are limited studies examining these outcomes. We sought to define the prognostic factors, clinical courses, and outcomes of children treated on Children's Oncology Group (COG) clinical trials with RMS metastatic to bone at diagnosis. METHODS: We performed a retrospective analysis of patients diagnosed with bone metastatic RMS enrolled on COG RMS clinical trials (D9802, D9803, ARST0431, or ARST08P1) between 1997 and 2013. RESULTS: RMS metastatic to bone was identified in 154 patients at a median age of 14.9 years at diagnosis. Fifty-eight percent of patients were male, 90% had metastases at additional sites, 74% had alveolar histology, and extremity was the most common primary site (31%). Eighty-six percent of patients (n = 133) received radiation therapy. The 3- and 5-year event-free survival (EFS) was 15.4% and 14.5%, respectively. The 3- and 5-year overall survival (OS) was 30.4% and 18.0%, respectively. We identified alveolar histology, FOXO1 fusion presence, unfavorable primary location, higher Oberlin score, and lack of radiation as poor prognostic characteristics for both EFS and OS in univariate analysis. Lack of radiation was not significant when excluding patients with events prior to 20 weeks. CONCLUSIONS: This study is the largest analysis of patients with bone metastatic RMS, and defines the poor overall outcomes and negative prognostic factors for these patients. They may be eligible for therapy deintensification for improved quality of life or pursuit of novel treatments/approaches, which are desperately needed.

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