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We aimed to assess the value of dose distribution-based dosiomics and planning computed tomography-based radiomics to predict radiation-induced temporal lobe injury (TLI) and guide individualized intensity modulated radiation therapy.A total of 5599 nasopharyngeal carcinoma patients were enrolled, including 2503, 1072, 988, and 1036 patients in the training, validation, prospective test, and external test cohorts, respectively. The concordance index (C-index) was used to compare the performance of the radiomics and dosiomics models with that of the quantitative analyses of normal tissue effects in the clinic and Wen's models. The predicted TLI-free survival rates of redesigned simulated plans with the same dose-volume histogram but different dose distributions for same patient in a cohort of 30 randomly selected patients were compared by the Wilcoxon matched-pairs signed-rank test.The radiomics and dosiomics signatures were constructed based on 30 selected computed tomography features and 10 selected dose distribution features, respectively, which were important predictors of TLI-free survival (all P.001). However, the radiomics signature had a low C-index. The dosiomics risk model combining the dosiomics signature, DThe dosiomics risk model was superior to traditional models in predicting the risk of TLI. This is a promising approach to precisely predict radiation-induced toxicities and guide individualized intensity modulated radiation therapy.

Hereditary uterine cancer (UC) is traditionally associated with pathogenic/likely pathogenic germline variants (PGVs) in Lynch syndrome genes or PTEN; however, growing evidence supports a role for other genes that may reveal new clinical management options. In this study we assessed the prevalence and potential clinical impact of PGVs identified in UC patients referred for comprehensive germline genetic testing that combined testing for Lynch syndrome, PTEN, and other cancer predisposition genes.Prevalence of PGVs in patients referred to a single clinical lab for germline genetic testing with an indication of uterine or endometrial cancer were retrospectively assessed and compared by syndrome type, patient age at testing, and self-reported ancestry. Potential clinical actionability of PGVs was based on established guidelines for clinical management, targeted therapies, and clinical trial eligibility.PGVs were detected in 13.6% of the cohort (880/6490). PGVs were most frequently observed in Lynch syndrome genes (60.4%) and PTEN (1.5%), with 38.1% in another cancer predisposition gene (i.e., CHEK2, BRCA1/BRCA2). PGV prevalence was similar for patients50 years and those ≥50 years (15.1% vs 13.2%). Nearly all PGVs (97.2%) were associated with guideline-recommended management, including cascade testing; 60.5% were associated with FDA-approved therapies; and 35.2% were associated with clinical trials.Focusing germline testing on Lynch syndrome genes and PTEN and limiting testing to patients50 years of age at diagnosis may overlook a substantial proportion of UC patients who harbor actionable PGVs. Universal comprehensive genetic testing of UC patients could benefit many patients and at-risk family members.

Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in mammals is a multifunctional protein. In this study, PCSK9 of marine fish Epinephelus coioides was characterized. The full-length cDNA of E. coioides PCSK9 was 2458 bp in length containing 185 bp 5' UTR, 263 bp 3' UTR and 2010 bp open reading frame (ORF) encoding 669 amino acids with the predicted molecular weight of 71 kDa and the theoretical PI of 6.6. Similar to other members of PCSK9 family, E. coioides PCSK9 has three conserved domains: Inhibitor_ I9 super family, Peptidases_ S8_ PCSK9_ Proteinase K_ like, and PCSK9_ C-CRD super family. E. coioides PCSK9 mRNA could be detected in all the tissues examined by real-time quantitative PCR, with the highest expression in the brain, followed by skin, trunk kidney, head kidney, intestine, blood, liver, spleen, gill, muscle and heart. E. coioides PCSK9 was distributed in both the cytoplasm and nucleus. The expression of E. coioides PCSK9 was significantly upregulated during Singapore grouper iridovirus (SGIV) infection. Upregulated PCSK9 could significantly affect the activities of nuclear factor kappaB (NF-κB) promoter, SGIV-induced apoptosis, and the expressions of the key SGIV genes (ICP18, LITAT, MCP, and VP19) and the E. coioides proinflammatory factors (IL-6, IL-1β, IL-8, and TNF-α). The results illustrated that E. coioides PCSK9 might be involved in the pathogen infection by regulating the innate immune response.

The efficiency of photocatalytic solar hydrogen evolution closely depends on the charge separation and the effective use of visible light. In this work, a highly efficient photocatalyst SiO/ZnCdS/NiS was synthesized through the self-assembly (ZnCdS loading to SiO) and photo-deposition method (NiS loading to ZnCdS). The synergistic effect of SiO and NiS NPs can effectively promote photoelectron generation and separation, thereby enhancing photocatalytic performance. The hydrogen production activity of the efficient photocatalyst was as high as 8.4 mmol gh under visible light (λ > 420 nm), 8.4 times of SiO/ZnCdS, 4.4 times of ZnCdS/NiS and 2.6 times of SiO/ZnCdS/Pt. DFT calculations indicate that NiS, as a catalytic center, is beneficial for electron accumulation and further improves the hydrogen evolution. Meanwhile, loading of NiS to ZnCdS also improves the water adsorption capacity of photocatalyst, which is conducive to photocatalytic water decomposition., This work was supported by the National Natural Science Foundation of China (21976111), Shandong Provincial Natural Science Foundation (ZR2019MB052).

The clinical utility of Dixon water-fat separation coronary MR angiography (CMRA) with compressed sensing (CS) reconstruction has not been determined in a patient population. This study was designed to evaluate the performance of 3.0 T non-contrast-enhanced Dixon water-fat separation CS whole-heart CMRA sequence in vitro and in vivo.In vitro phantom MRI, we compared key parameters of the SENSE and CS images. And in this prospective in vivo study, from November 2019 to October 2020, 94 participants were recruited for 3.0 T non-contrast-enhanced Dixon water-fat separation CS whole-heart CMRA. The accuracy of CMRA for detecting a ≥ 50% reduction in diameter was determined using X-ray coronary angiography (CA) as the reference method.Compared with SENSE, CS with an appropriate acceleration factor offers both higher SNR/CNR (p0.05) and a shortened acquisition. Fifty-eight patients successfully completed the CMRA and CA. The sensitivity, specificity, positive predictive values, negative predictive values, and accuracy of 3.0 T non-contrast-enhanced Dixon water-fat separation CS whole-heart CMRA according to a patient-based analysis were 96.4%, 66.7%, 73.0%, 95.2% and 81.0%, respectively. The area under the receiver-operator characteristic (ROC) curve (AUC) of 3.0 T non-contrast-enhanced Dixon water-fat separation CS whole-heart CMRA for detecting significant coronary artery stenosis is 0.908, 0.895, and 0.904 in patient-, vessel-, and segment-based analyses respectively.3.0 T non-contrast-enhanced Dixon water-fat separation whole-heart CMRA using appropriate CS is a promising noninvasive and radiation-free technique to detect clinically significant coronary stenosis on patients with suspected CAD.

Recently, the highly ordered J-aggregates of organic dyes with intriguing optical properties have received considerable attention in biomedical applications. Herein, binary metal ions Mn(II)/Fe(III) are used to induce the formation of indocyanine green (ICG) J-aggregates. Further, the sheet-like J-aggregates are able to act as "carriers" for loading hydrophobic chemotherapeutic gambogic acid (GA), realizing the effect of "killing two birds with one stone" for both treatment and delivery. The as-designed nanoassembly is formed spontaneously in aqueous environment

To develop and validate a radiomics nomogram for differentiating between malignant pulmonary nodules and benign nodules.56 benign and 51 malignant nodules from 96 patients were analyzed using manual segmentation of the T2-fBLADE-TSE, while the nodules signal intensity (SIlesion), lesion muscle ratio (LMR) and nodule size were all measured and recorded. The maximum relevance and minimum redundancy (mRMR) and the least absolute shrinkage and selection operator (LASSO) were used to select nonzero coefficients and develop the model in pulmonary nodules diagnosis. The radiomics nomogram was also developed. The clinical prediction value was determined by the decision curve analysis (DCA).The nodule size, SIlesion and LMR of the benign group were 1.78 ± 0.57 cm, 227.50 ± 81.39 and 2.40 ± 1.27 respectively, in contrast to the 2.00 ± 0.64 cm, 232.87 ± 82.21 and 2.17 ± 0.91, respectively, in the malignant group (P = 0.09, 0.60 and 0.579). A total of 13 radiomics features were retained. The Rad-score of the benign nodules group was lower than that of the malignant nodules group (P0.0010.049, trainingtest set). The AUC of radiomics signature for nodules diagnosis was 0.82 (95% CI, 0.73-0.91) in the training set and 0.71 (95% CI, 0.51-0.90) in the test set. A nomogram, consisting of 13 radiomics features and nodule size, produced good prediction in the training set (AUC, 0.82; 95% CI, 0.73-0.91), which was significantly better than that of T2-based quantitative parameters (AUC, 0.62; 95% CI, 0.50-0.75, P = 0.003). In the test set, the performance of radiomics nomogram (AUC, 0.70; 95% CI, 0.51-0.90) was also better than that of T2-based quantitative parameters (AUC, 0.46; 95% CI, 0.25-0.67) (P = 0.145). The DCA showed that radiomics nomogram and T2-based quantitative parameter had overall net benefits, while the performance of nomogram was better.We constructed and validated a T2-fBLADE-TSE-based radiomics nomogram that can help to differentiate between malignant pulmonary nodules and benign nodules.

The popularity of smartphones and the advent of GPS positioning and wireless communication technologies in the recent decade have facilitated large-scale implementations of dynamic ridepooling services, such as Uber Pool, Lyft Line, and Didi Pinche. As in such services trips usually start before the appearance of pooling partners, knowing the probability of getting matching with another order (i.e., matching probability), the expected detour distance, and the expected shared distance before the start of each trip is essential for passengers to evaluate their willingness to pool and for ridepooling platforms to offer attractive discounts. In this paper, assuming that every ridepooling passenger shares vehicle space with at most one another during the entire trip, and ridepooling orders in each (origin-destination) OD pair appear following a Poisson process with a given rate, we propose a mathematical modeling approach to predict the matching probability, the expected ride distance, and the expected shared distance of each order under a first-come-first-serve strategy in dynamic ridepooling service. The method defines unmatched passengers at different locations along the exclusive-riding path of each OD pair into different seeker- and taker-states, formulates the complex interdependency of the matching probabilities, matching rates and arrival rates of (unmatched) passengers in different states into a system of nonlinear equations, and generates the matching probabilities and expected ride/shared distances of all OD pairs simultaneously. Under the same first-come-first-serve strategy, we simulated the occurrence, movements and state transitions of ridepooling orders based on a 30*30 grid network and the real network of Haikou City in China. In comparison with simulation results, we show that the method proposed in this paper can generate fairly satisfactory predictions under diverse matching conditions and demand intensities.

Detrimental tumor microenvironment (TME) relies on distorted tumor vasculature for further tumor expansion. Vascular normalization therapy partly improves TME through vessel repairing, while these therapies enter an unbreakable Mobius ring due to each attempt hindered by pro-angiogenic factors from TME, leading to limited duration and extent of vascular normalization. Here, we developed a nanosystem including FLG and MAR/MPA nanodrugs to regulate both tumor vasculature and TME. FLG nanodrugs were constructed by connecting VEGF/VEGFR2 inhibitory low molecular weight heparin and gambogic acid with F3 peptide decoration for directly regulating on vascular endothelial cells and inducing vascular normalization. Meanwhile, MAR/MPA nanodrugs encapsulating CCL5/CCR5 blocker maraviroc were designed to restrict cytokine functions of angiogenesis and TME deterioration, contributing to vasculature repairing and TME reconstruction. Our results demonstrated this combined nanosystem synergistically induced vascular normalization window lasting 9 days and restored vascular permeability and oxygen supply in Panc-1 tumor. Furthermore, in melanoma, our nanosystem achieved immune improvements with increased infiltration of CD4+ and CD8+T cells in a remodeled TME. The two nanodrugs assisting each other in terms of both vascular repairing and TME improvements successfully reversed the vicious crosstalk to a positive one, achieving overall TME remodeling and promoting therapeutic efficiency.