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Head and neck squamous cell carcinoma (HNSC) is the sixth most common cancer worldwide, and new cases are anticipated to reach 1.08 million in 2030. Our study aimed to identify the competing endogenous RNAs (ceRNAs) involved in HNSC tumorigenesis.First, a pan-cancer correlation analysis was conducted on the expression and survival conditions of sideroflexin (The pan-cancer analysis suggested thatBy performing ceRNA analysis, our study demonstrated that MIR193HG-miR-29c-3p

Objective To investigate the influence of different volume of interest (VOI) delineation strategies on machine learning-based predictive models for discrimination between low and high nuclear grade clear cell renal cell carcinoma (ccRCC) on dynamic contrast-enhanced CT. Methods This study retrospectively collected 177 patients with pathologically proven ccRCC (124 low-grade; 53 high-grade). Tumor VOI was manually segmented, followed by artificially introducing uncertainties as: (i) contour-focused VOI, (ii) margin erosion of 2 or 4 mm, and (iii) margin dilation (2, 4, or 6 mm) inclusive of perirenal fat, peritumoral renal parenchyma, or both. Radiomics features were extracted from four-phase CT images (unenhanced phase (UP), corticomedullary phase (CMP), nephrographic phase (NP), excretory phase (EP)). Different combinations of four-phasic features for each VOI delineation strategy were used to build 176 classification models. The best VOI delineation strategy and superior CT phase were identified and the top-ranked features were analyzed. Results Features extracted from UP and EP outperformed features from other single/combined phase(s). Shape features and first-order statistics features exhibited superior discrimination. The best performance (ACC 81%, SEN 67%, SPE 87%, AUC 0.87) was achieved with radiomics features extracted from UP and EP based on contour-focused VOI. Conclusion Shape and first-order features extracted from UP + EP images are better feature representations. Contour-focused VOI erosion by 2 mm or dilation by 4 mm within peritumor renal parenchyma exerts limited impact on discriminative performance. It provides a reference for segmentation tolerance in radiomics-based modeling for ccRCC nuclear grading. Key points • Lesion delineation uncertainties are tolerated within a VOI erosion range of 2 mm or dilation range of 4 mm within peritumor renal parenchyma for radiomics-based ccRCC nuclear grading. • Radiomics features extracted from unenhanced phase and excretory phase are superior to other single/combined phase(s) at differentiating high vs low nuclear grade ccRCC. • Shape features and first-order statistics features showed superior discriminative capability compared to texture features.

An efficient and simple approach for stereoselective synthesis of β-Kdo C-glycosides was described, which relies on easily available peracetylated anomeric acetate or anomeric 2-pyridyl sulfide to couple with carbonyl compounds via SmI2-mediated Reformatsky reactions. The utility of this methodology is exemplified by the streamlined synthesis of a practical β-Kdo C-glycoside with an anomeric aminopropyl linker to conjugate with other biomolecules for further biological studies.

Developing novel activatable photosensitizers with excellent plasma membrane targeting ability is urgently needed for smart photodynamic therapy (PDT). Herein, a tumor acidity-activatable photosensitizer combined with a two-step bioorthogonal pretargeting strategy to anchor photosensitizers on the plasma membrane for effective PDT is developed. Briefly, artificial receptors are first anchored on the cell plasma membrane using cell-labeling agents (Az-NPs) via the enhanced permeability and retention effect to achieve the tumor cell labeling. Then, pH-sensitive nanoparticles (S-NPs) modified with dibenzocyclooctyne (DBCO) and chlorin e6 (Ce6) accumulate in tumor tissue and disassemble upon protonation of their tertiary amines in response to the acidic tumor environment, exposing the contained DBCO and Ce6. The selective, highly specific click reactions between DBCO and azide groups enable Ce6 to be anchored on the tumor cell surface. Upon laser irradiation, the cell membrane is severely damaged by the cytotoxic reactive oxygen species, resulting in remarkable cellular apoptosis. Taken together, the membrane-localized PDT by our bioorthogonal pretargeting strategy to anchor activatable photosensitizers on the plasma membrane provides a simple but effective method for enhancing the therapeutic efficacy of photosensitizers in anticancer therapy.

The codelivery of drugs at specific optimal ratios to cancer cells is vital for combination chemotherapy. However, most of the current strategies are unable to coordinate the loading and release of drug combinations to acquire precise and controllable synergistic ratios. In this work, we designed an innovative dual-drug backboned and reduction-sensitive polyprodrug PEG-P(MTO-ss-CUR) containing the anticancer drugs mitoxantrone (MTO) and curcumin (CUR) at an optimal synergistic ratio to reverse drug resistance. Due to synchronous drug activation and polymer backbone degradation, drug release at the predefined ratio with a synergistic anticancer effect was demonstrated by in vitro and in vivo experiments. Therefore, the dual-drug delivery system developed in this work provides a novel and efficient strategy for combination chemotherapy.

BackgroundFew reports have been conducted to comparing surgical results and safety evaluations between the different types of infections in geriatric patients with thoracolumbar infections. The aim of this study is to investigate the safety and efficacy of surgical treatment for thoracolumbar infections in elderly patients.Methods21 patients with pyogenic spondylodiscitis (PS) and 26 patients with tuberculous spondylodiscitis (TS) were enrolled in the study. All patients were treated using one-stage posterior debridement, decompression, and pedicle screw fixation. Comparison of operative safety parameters between the two groups. Clinical efficacy was evaluated using visual analogue scale (VAS) score, the American Spinal Injury Association (ASIA) grade, the short form (SF)-36 survey and Oswestry disability index (ODI) to determine patient quality of life pre- and post-operatively. Results Hospitalisation and intensive care unit duration in the PS group were significantly shorter than in the TS group (PConclusionOne-stage posterior debridement, decompression, interbody fusion, and internal fixation can be considered a safe and effective method of treating spinal infections in the elderly. This method can improve nerve function, reconstruct spinal stability, and enhance the quality of life of elderly patients. Both PS and TS who underwent surgery achieve similar clinical and radiological results.

BackgroundFew reports have been conducted to comparing surgical results and safety evaluations between the different types of infections in geriatric patients with thoracolumbar infections. The aim of this study is to investigate the safety and efficacy of surgical treatment for thoracolumbar infections in elderly patients.Methods21 patients with pyogenic spondylodiscitis (PS) and 26 patients with tuberculous spondylodiscitis (TS) were enrolled in the study. All patients were treated using one-stage posterior debridement, decompression, and pedicle screw fixation. Comparison of operative safety parameters between the two groups. Clinical efficacy was evaluated using visual analogue scale (VAS) score, the American Spinal Injury Association (ASIA) grade, the short form (SF)-36 survey and Oswestry disability index (ODI) to determine patient quality of life pre- and post-operatively. Results Hospitalisation and intensive care unit duration in the PS group were significantly shorter than in the TS group (PConclusionOne-stage posterior debridement, decompression, interbody fusion, and internal fixation can be considered a safe and effective method of treating spinal infections in the elderly. This method can improve nerve function, reconstruct spinal stability, and enhance the quality of life of elderly patients. Both PS and TS who underwent surgery achieve similar clinical and radiological results.

The study’s objectives were to examine the effects of electrofusion on rabbit somatic cell nuclear transfer (SCNT) embryos, and to test melatonin as a protective agent against electrofusion damage to SCNT embryos. The levels of reactive oxygen species (ROS), the epigenetic state (H3K9me3), and the content of endoplasmic reticulum (ER) stress-associated transcripts (IRE-1 and CHOP) were measured. Melatonin was added during the preimplantation development period. The total blastocyst cell numbers were counted, and the fragmentation rate and apoptotic index were determined and used to assess embryonic development. Electrofusion increased (1) ROS levels at the 1-, 2-, 4-, and 8-cell stages; (2) H3K9me3 levels at the 2-, 4-, and 8-cell stage; and (3) the expression of IRE-1 and CHOP at the 8-cell, 16-cell, morula, and blastocyst stages. The treatment of SCNT embryos with melatonin significantly reduced the level of ROS and H3K9me3, and the expression levels of IRE-1 and CHOP. This treatment also significantly reduced the fragmentation rate and apoptotic index of blastocysts and increased their total cell number. In conclusion, the electrofusion of rabbit SCNT embryos induced oxidative stress, disturbed the epigenetic state, and caused ER stress, while melatonin reduced this damage. Our findings are of signal importance for improving the efficiency of SCNT and for optimizing the application of electrical stimulation in other biomedical areas.

(1) To evaluate the diagnostic performance of radiomics in differentiating high-grade glioma from brain metastasis and how to improve the model. (2) To assess the methodological quality of radiomics studies and explore ways of embracing the clinical application of radiomics.Studies using radiomics to differentiate high-grade glioma from brain metastasis published by 26 July 2021 were systematically reviewed. Methodological quality and risk of bias were assessed using the Radiomics Quality Score (RQS) system and Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool, respectively. Pooled sensitivity and specificity of the radiomics model were also calculated.Seventeen studies combining 1,717 patients were included in the systematic review, of which 10 studies without data leakage suspicion were employed for the quantitative statistical analysis. The average RQS was 5.13 (14.25% of total), with substantial or almost perfect inter-rater agreements. The inclusion of clinical features in the radiomics model was only reported in one study, as was the case for publicly available algorithm code. The pooled sensitivity and specificity were 84% (95% CI, 80-88%) and 84% (95% CI, 81-87%), respectively. The performances of feature extraction from the volume of interest (VOI) or (semi) automatic segmentation in the radiomics models were superior to those of protocols employing region of interest (ROI) or manual segmentation.Radiomics can accurately differentiate high-grade glioma from brain metastasis. The adoption of standardized workflow to avoid potential data leakage as well as the integration of clinical features and radiomics are advised to consider in future studies.• The pooled sensitivity and specificity of radiomics for differentiating high-grade gliomas from brain metastasis were 84% and 84%, respectively. • Avoiding potential data leakage by adopting an intensive and standardized workflow is essential to improve the quality and generalizability of the radiomics model. • The application of radiomics in combination with clinical features in differentiating high-grade gliomas from brain metastasis needs further validation.

Asymmetric functionalization of the C(sp

Simple Summary Glioblastoma multiforme (GBM) and solitary brain metastasis (SBM) are common brain tumors in adults. The two tumors often pose a diagnostic dilemma owing to their similar features on conventional magnetic resonance imaging (MRI). Ability to discriminate the two tumors is critical as it informs clinical treatment strategies. This pilot study attempts to employ the machine learning technique to identify GBM and SBM by fusing radiomics features of multiple MRI sequences and multiple models. A multiparametric MR-based RadioFusionOmics (RFO) model was developed and has demonstrated promising prediction accuracy for the identifications of GBM and SBM. Abstract This study aimed to evaluate the diagnostic potential of a novel RFO model in differentiating GBM and SBM with multiparametric MR sequences collected from 244 (131 GBM and 113 SBM) patients. Three basic volume of interests (VOIs) were delineated on the conventional axial MR images (T1WI, T2WI, T2_FLAIR, and CE_T1WI), including volumetric non-enhanced tumor (nET), enhanced tumor (ET), and peritumoral edema (pTE). Using the RFO model, radiomics features extracted from different multiparametric MRI sequence(s) and VOI(s) were fused and the best sequence and VOI, or possible combinations, were determined. A multi-disciplinary team (MDT)-like fusion was performed to integrate predictions from the high-performing models for the final discrimination of GBM vs. SBM. Image features extracted from the volumetric ET (VOIET) had dominant predictive performances over features from other VOI combinations. Fusion of VOIET features from the T1WI and T2_FLAIR sequences via the RFO model achieved a discrimination accuracy of AUC = 0.925, accuracy = 0.855, sensitivity = 0.856, and specificity = 0.853, on the independent testing cohort 1, and AUC = 0.859, accuracy = 0.836, sensitivity = 0.708, and specificity = 0.919 on the independent testing cohort 2, which significantly outperformed three experienced radiologists (p = 0.03, 0.01, 0.02, and 0.01, and p = 0.02, 0.01, 0.45, and 0.02, respectively) and the MDT-decision result of three experienced experts (p = 0.03, 0.02, 0.03, and 0.02, and p = 0.03, 0.02, 0.44, and 0.03, respectively).

Photodynamic therapy (PDT) is a promising non-invasive and selective cancer treatment. However, its efficacy is curtailed by tumor hypoxia and high levels of glutathione (GSH) in the tumor and addressing both limitations simultaneously remain challenging. Here, an all-in-one nanoplatform was designed using a GSH-responsive nitric oxide (NO) nano-prodrug that synchronously depletes GSH and relieves hypoxia in tumors, enhancing PDT efficacy. The nano-prodrug PEG-PAMAM-PA/SNO was prepared by integrating the GSH-sensitive NO and pheophorbide A (PA) prodrugs N-acetyl-d-penicillamine thiolactone and PAMAM-PA into polyethylene glycol (PEG), and the NP

As a promising new form of non-apoptotic regulated cell death, ferroptosis has potential as an effective supplement to apoptosis-based cancer treatments. However, high intracellular glutathione (GSH) levels and insufficient hydrogen peroxide (H2O2) in the tumor limit the efficacy of ferroptosis. Here, we designed a theranostic nanoplatform, named FCS/GCS, by incorporating amphiphilic polymer skeletal (P-SS-D), cinnamaldehyde prodrug (CA-OH) and iron ions (Fe3+)/gadolinium ions (Gd3+) via chelation reactions between Fe3+/Gd3+ and polyphenols. When delivered in the tumor microenvironment with high GSH level, the nanoparticles are depolymerized by the poly(disulfide) backbone of P-SS-D. The activated CA consumes the GSH and elevates intracellular H2O2, followed by a high level of Fenton reaction to generate abundant •OH levels. The generation of reactive oxygen species (ROS) further accelerates CA activation. The GSH consumption by disulfide, CA and Fe3+, downregulates GPX4 and generates •OH, which accelerate lipid peroxides (LPO) accumulation and consequently enhances ferroptosis. Additionally, the released Gd3+ may serve as a contrast agent for tumor-specific T1-weighted magnetic resonance imaging (MRI). Thus, the rationally designed FCS/GCS system is a promising strategy for effective MRI-based visual ferroptosis therapy. Statement of significance : Ferroptosis is a new form of non-apoptotic regulated cell death and has potential as an effective supplement to apoptosis-based cancer treatment. However, the efficiency of ferroptosis is limited by excessive glutathione level and insufficient hydrogen peroxide level in tumor site. In this study, we fabricate a theranostic nanoplatform (FCS/GCS) to amplify oxidation stress in tumor site for effective ferroptosis-based cancer treatment, and tumor specific magnetic resonance imaging is introduced for supervision. Our nanoplatform may provide a promising strategy for MRI-based visual ferroptosis therapy with high specificity and efficiency.

Tirofiban is a highly selective nonpeptide antagonist of glycoprotein IIb/IIIa receptor, which reversibly inhibits platelet aggregation. It remains uncertain whether intravenous tirofiban is effective to improve functional outcomes for patients with large vessel occlusion ischemic stroke undergoing endovascular thrombectomy.To assess the efficacy and adverse events of intravenous tirofiban before endovascular thrombectomy for acute ischemic stroke secondary to large vessel occlusion.This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 55 hospitals in China, enrolling 948 patients with stroke and proximal intracranial large vessel occlusion presenting within 24 hours of time last known well. Recruitment took place between October 10, 2018, and October 31, 2021, with final follow-up on January 15, 2022.Participants received intravenous tirofiban (n = 463) or placebo (n = 485) prior to endovascular thrombectomy.The primary outcome was disability level at 90 days as measured by overall distribution of the modified Rankin Scale scores from 0 (no symptoms) to 6 (death). The primary safety outcome was the incidence of symptomatic intracranial hemorrhage within 48 hours.Among 948 patients randomized (mean age, 67 years; 391 [41.2%] women), 948 (100%) completed the trial. The median (IQR) 90-day modified Rankin Scale score in the tirofiban group vs placebo group was 3 (1-4) vs 3 (1-4). The adjusted common odds ratio for a lower level of disability with tirofiban vs placebo was 1.08 (95% CI, 0.86-1.36). Incidence of symptomatic intracranial hemorrhage was 9.7% in the tirofiban group vs 6.4% in the placebo group (difference, 3.3% [95% CI, -0.2% to 6.8%]).Among patients with large vessel occlusion acute ischemic stroke undergoing endovascular thrombectomy, treatment with intravenous tirofiban, compared with placebo, before endovascular therapy resulted in no significant difference in disability severity at 90 days. The findings do not support use of intravenous tirofiban before endovascular thrombectomy for acute ischemic stroke.Chinese Clinical Trial Registry Identifier: ChiCTR-IOR-17014167.

Shengsheng Lai,1,* Lei Sun,2,* Jialiang Wu,3 Ruili Wei,4 Shiwei Luo,4 Wenshuang Ding,5 Xilong Liu,6 Ruimeng Yang,4 Xin Zhen2 1School of Medical Equipment, Guangdong Food and Drug Vocational College, Guangzhou, Guangdong, 510520, People’s Republic of China; 2School of Biomedical Engineering, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 3Department of Radiology, The University of Hong Kong Shenzhen Hospital, Shenzhen, Guangdong, 518000, People’s Republic of China; 4Department of Radiology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510180, People’s Republic of China; 5Department of Pathology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510180, People’s Republic of China; 6Department of Radiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ruimeng YangDepartment of Radiology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510180, People’s Republic of ChinaTel +86-20-81048873Email eyruimengyang@scut.edu.cnXin ZhenSchool of Biomedical Engineering, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of ChinaTel +86-20-62789323Email xinzhen@smu.edu.cnObjective: To investigate the predictive performance of different machine learning models for the discrimination of low and high nuclear grade clear cell renal cell carcinoma (ccRCC) by using multiphase computed tomography (CT)-based radiomic features.Materials and Methods: A total of 137 consecutive patients with pathologically proven ccRCC (including 96 low-grade [grade 1 or 2] and 41 high-grade [grade 3 or 4] ccRCC) from January 2011 to January 2019 were enrolled in this retrospective study. Target region of interest (ROI) delineation followed by texture extraction was performed on a representative slice with the largest section of the tumor on the four-phase (unenhanced phase [UP], corticomedullary phase [CMP], nephrographic phase [NP] and excretory phase [EP]) CT images. Fifteen concatenations of the four-phase features were fed into 176 classification models (built with 8 classifiers and 22 feature selection methods), the classification performances of the 2640 resultant discriminative models were compared, and the top-ranked features were analyzed.Results: Image features extracted from the unenhanced phase (UP) CT images demonstrated a dominant classification performance over features from the other three phases. The discriminative model “Bagging + CMIM” achieved the highest classification AUC of 0.75. The top-ranked features from the UP included one shape-based feature and five first-order statistical features.Conclusion: Image features extracted from the UP are more effective than other CT phases in differentiating low and high nuclear grade ccRCC based on machine learning–based classification modeling.Keywords: clear cell renal cell carcinoma, Fuhrman nuclear grade, computed tomography, machine learning, classification

Embryo culture conditions are crucial as they can affect embryo quality and even offspring. Oviductal extracellular vesicles (EVs) long been considered a major factor influencing interactions between the oviduct and embryos, and thus its absence is associated with inferior embryonic development in in vitro culture. Herein, we demonstrated that melatonin is present in oviduct fluids and oviduct fluid‐derived EVs. Addition of either EVs (1.87 × 1011 particles/mL) or melatonin (340 ng/mL) led to a significant downregulation of reactive oxygen species (ROS) and 5‐methylcytosine (5‐mC), as well as an increase in the blastocyst rate of embryos, which was inhibited by the addition of luzindole—a melatonin receptor agonist. A combination of EVs (1.87 × 1010 particles/mL) and melatonin (at 34.3 pg/mL) led to the same results as well as a significant decrease in the apoptosis index and increase in the inner cell mass (ICM)/trophectoderm (TE) index. These results suggest that an EV‐melatonin treatment benefits embryonic development. Our findings provide insights into the role of EVs and melatonin during cell communication and provide new evidence of the communication between embryos and maternal oviduct.

SummaryRabbits play an important role in people’s lives due to their high nutritional value and high-quality hair that can be used as raw material for textiles. Furthermore, rabbits are an important animal model for human disease, as genome-edited animals are particularly valuable for studying gene functions and pathogenesis. Somatic cell nuclear transfer (SCNT) is an important technique for producing genome-edited animals and it has great value in saving endangered species and in clone stem cell therapy. However, the low efficiency of SCNT limits its application, with the selection of suitable rabbit oocytes being crucial to its success. In the present study, we collected oocytes from ovarian follicles and stained them with 26 μM brilliant cresyl blue (BCB). We then matured the oocytes in vitro and used them for SCNT. Comparison of the BCB-positive oocytes with BCB-negative oocytes and the control group showed that the BCB-positive group had a significantly higher maturation rate (81.4% vs. 48.9% and 65.3% for the negative and control groups, respectively), cleavage rate (86.6% vs. 67.9% and 77.9%), blastocyst rate (30.5% vs. 12.8% and 19.6%), total number of blastocysts (90±7.5 vs. 65.3±6.3 and 67.5±5.7), and inner cell mass (ICM)/ trophectoderm (TE) index (42.3±4.2 vs. 30.2±2.1 and 33.9±5.1) (PPin vitro, indicating that BCB staining is a reliable method for selecting oocytes to enhance the efficiency of SCNT.

Chinese historical documents recorded plenty of information related with climate change and grain harvest, which are helpful to explore the impacts of extreme drought/flood on crops and the implications on adaptation for agriculture to more extreme climate probability in the context of global warming. Here, we used the reconstructed extreme drought/flood chronologies and reconstructed grain harvest series derived from historical documents to investigate the connection between the occurrences of extreme drought/flood in eastern China and poor harvest during 801–1910. The results showed that more extreme droughts occurred in 801–870, 1031–1230, 1481–1530 and 1581–1650 over whole eastern China. On regional scale, more extreme droughts occurred in 1031–1100, 1441–1490, 1601–1650 and 1831–1880 in North China, 801–870, 1031–1120, 1161–1220 and 1471–1530 in Jianghuai, 991–1040, 1091–1150, 1171–1230, 1411–1470 and 1481–1530 in Jiangnan. The grain harvest was poor in periods of 801–940, 1251–1650 and 1841 to 1910, but bumper in periods of 951–1250 and 1651–1840 approximately. For entire period of 801–1910, more occurrence of extreme drought in any sub–region of eastern China could significantly reduce harvest in the long term average, but the connection between harvest and extreme flood seemed to be much weaker. The co–occurrence of extreme drought and extreme flood in different sub–regions in the same year had a greater impact on harvest yield. However, the connection between the occurrence of poor harvest and regional extreme drought was weak in the warm epoch of 920–1300 but strong in the cold epoch of 1310–1880, which implicated warm climate might weaken the impact of extreme drought on poor harvest during historical times.

With the rapid development of global tourism, identifying the vulnerability of tourism-based social-ecological systems (SESs) has become an important topic in sustainable development research. This study aimed to quantitatively evaluate the vulnerability, spatiotemporal evolution characteristics, and influencing factors of tourism-based SESs in the counties of the Three Gorges Reservoir Area (TGRA). A comprehensive evaluation system containing 46 indicators was constructed using a model that combines a social–economic–ecological model and a pressure–state–response model (SEE-PSR). The entropy and composite index methods were used to calculate the vulnerability values of the indicators, and Geodetector was used to explore the factors influencing system vulnerability in the whole study area. The results showed the following: (1) The mean value of the composite vulnerability index of the TGRA from 2010 to 2018 was 0.4849, indicating a moderate vulnerability state. The system vulnerability of the study area gradually decreased from moderately high to moderately low. (2) There were obvious differences in the spatiotemporal evolution of vulnerability in different counties, high and moderately high vulnerability continued to decrease, moderately low and low vulnerability increased, and moderate vulnerability showed a trend of increasing and then decreasing. Meanwhile, the relative differences in vulnerability among counties were small but gradually increasing. (3) System vulnerability was mainly caused by the social subsystem. Six factors, including the growth rate of the number of tourists and the amount of fiscal expenditure, were more likely to contribute to system vulnerability than other factors. The interaction types were mainly nonlinear enhancement types, supplemented by two-factor enhancement. This study presents an approach for evaluating the vulnerability of tourist destinations and constructing an evaluation index system. In this way, it has reference value for reducing regional vulnerability and promoting sustainable development.

Purpose This study assesses the clinical value of dual-energy computed tomography (DECT) in the early diagnosis of intracranial hemorrhage and evaluates the risk of hemorrhagic transformation in patients with acute ischemic stroke (AIS) after mechanical thrombectomy. Methods Patients with AIS who have undergone thrombectomy with Solitaire stent and DECT within one hour after surgery were prospectively enrolled. Linear mixed energy images, virtual non-contrast (VNC) image, and iodine overlay map (IOM) were obtained. Routine CT scan was performed 24 h postoperatively. The sensitivity, specificity, positive and negative predictive values, and accuracy of DECT in the early diagnosis of intracranial hemorrhage was evaluated. The iodine concentration of intracranial lesions was measured by IOM with the follow-up results taken as reference. Receiver operating characteristic (ROC) analysis was performed to obtain the threshold of hemorrhagic transformation and increased bleeding. Results Among the 44 patients enrolled in this study, 25 (56.8 %) were diagnosed with simple extravasation of iodinated contrast agent, and 19 (43.2 %) showed intracranial hemorrhage in DECT. Compared with the follow-up CT 24 h after surgery, early diagnosis of postoperative intracranial hemorrhage using DECT demonstrated a sensitivity of 90.5 %, specificity of 100 %, positive predictive rate of 100 %, negative predictive rate of 92.0 %, and accuracy of 95.5 %. Among the 86 intracranial lesions that underwent iodine concentration measurement, 19 were diagnosed with hemorrhagic transformation or increased bleeding, and 67 were diagnosed without the aforementioned conditions. The sensitivity and specificity for differentiating the two groups were 73.7 % and 92.5 %, respectively, with a cut-off value of 2.7 mg/mL. Conclusion DECT is clinically valuable in early diagnosis and prediction of intracranial hemorrhage after mechanical thrombectomy in AIS patients.

In recent years, the stimuli-responsive delivery of drugs based on diselenide-bridged polymeric nanocomposites have gathered significant attention from researchers towards augmented anticancer therapy, owing to the unique dual reactive oxygen species (ROS) as well as glutathione (GSH) redox-responsive diselenide bonds. Despite their success in delivery of diverse therapeutics, the fabrication of such diselenide-bridged polymeric nanocomposites with high performance efficiency is often limited due to the relatively high sensitivity of diselenide bonds to various stimuli such as light, temperature, and both oxidation and reduction. In an attempt to address these attributes, herein, we demonstrate the fabrication of indocyanine green (ICG)-loaded diselenide-containing polymeric nanoparticles using the supercritical fluid (SCF)-assisted rapid and facile synthesis approach for ROS/GSH-responsive drug delivery platform towards augmented anticancer therapy. Initially, the diselenide-containing poly (ethylene glycol)-poly(e-caprolactone)-poly(ethylene glycol) block copolymers (PSe) are synthesized based on stannous octoate initiated ring-opening polymerization and subsequent esterification with carboxylic acid-functionalized polyethylene glycol (PEG-COOH). Further, the ICG molecules are loaded into the copolymer nanocomposites via the incorporation of coprecipitation interactions between PSe and ICG through the convenient and highly effective SCF technology. These nanocomposites afforded high drug loading (up to 48.5%) and encapsulation efficiency (up to 85.1%), along with uniform distribution and desired photo-stability. Finally, various photodynamic therapy (PDT)-related experiments both in vitro and in vivo have shown that the fabricated ROS-responsive drug delivery system based on ICG and PSe is capable of devastating tumor cells.

Treated dentin matrix (TDM) as a kind of scaffolding material has been proved odontogenic induction ability on dental-derived stem cells. Given the limited resources of dental stem cells, it is necessary to seek new seed cell which easily obtained. Jaw bone marrow mesenchymal stem cell (JBMMSC) as non-dental-derived stem cell relates to the development of teeth and jaws which suggest us JBMMSCs could act as a new seed cell for tooth tissue engineering. To assess the odontogenic and osteogenic potential of JBMMSCs, cells were induced by TDM extraction in vitro and combined with TDM in vivo. Results were analyzed by PCR, Western Blotting and histology. PCR and Western Blotting showed odontogenic and osteogenic makers were significantly enhanced in varying degrees after induced by TDM extraction in vitro. In vivo, JBMMSCs expressed both odontogenic and osteogenic-related protein, and the latter showed stronger positive expression. Furthermore, histological examination of the harvested grafts was observed the formation of bone-like tissue. Therefore, osteogenic differentiation ability of JBMMSCs were enhanced significantly after being inducted by TDM which illustrates that non-odontogenic derived stem cells are still promising seed cells in tooth root tissue engineering.

Inter-disciplinary talents with one professional skill and proficient in English are the type of talents most lacking in the Chinese market and most desired by enterprises. This paper presents a definition for the “profession + English” inter-disciplinary talents, and analyzes the demand of this type of talents by the society. On this basis, factors affecting the training of this type of inter-disciplinary talents are analyzed, and methods to realize this training mode are discussed from five aspects.

The role of water and stereoselectivity in the direct syn-aldol reaction involving 3-pentanone and 4-nitrobenzaldehyde catalyzed by amino acid derivatives on water has been investigated by density functional theory. Calculations indicate that the formation of intermediate enamine is the rate determining step via a three-step process with activation enthalpies of 50 kcal/mol in the gas phase and 21 kcal/mol in the presence of water. The subsequent nucleophilic addition of enamine to aldehyde is relatively easier with activation enthalpies below 10 kcal/mol both in the gas phase and in the presence of water. The diastereoselective formation of syn- and anti-aldol products results from the preferential formation of Z-enamine to E-enamine, kinetically and thermodynamically. The enantioselectivity of both syn- and anti-products is controlled by the steric repulsive interactions between the amino alcohol moiety of catalyst and the phenyl ring of aldehyde. Calculations show that water molecule can act as a proton shuttle in the proton-transport catalytic processes. The water-assisted proton-transfer is very efficient to reduce the activation barriers via protonation and deprotonation in the formation of C-N and C-C bonds, dehydration, and β-elimination processes by inhibiting the generation of zwitterionic transition states. The theoretical discoveries indicate that in the present proton-transport assistance, the amino alcohol moiety of the catalyst plays a critical role as hydrogen bond donor to anchor substrates with carbonyl group close to the amine or enamine moiety so that the water molecule can bridge the NH of amine and the oxygen of carbonyl by hydrogen bonding interaction around the reactive site to activate the reactants and promote the reaction effectively.

Interface evaluations of four high-performance concrete overlays cast on top of one type of normal concrete substrate were made by a new direct shear test method. Two different surface preparations such as mechanical abrasion and chemical etching were followed to manufacture 64 overlay–substrate bi-layer specimens. This paper discusses the material properties and fabrication and evaluations of bi-layer specimens. Results show that successful interface bond characterization was possible through this direct shear apparatus. The test method seems to be suitable for screening and selection of various overlays for their compatibility with substrate concrete. However, some modification in the tool is needed for assessing the high-bond capacity interface. Effects of bonding slurry also needs further study.

As synthesis by combinatorial chemistry and high throughput screening have become well-established strategies in the drug discovery process, chemists face increased challenges in managing large amounts of data and using these data to design more diverse and focused libraries. As synthesis is an intuitive and empirical process, however, the classical approaches to computer-assisted synthesis planning do not fully satisfy the needs of the synthetic chemist. We describe a novel computational technique for extracting reaction data and building a generic reaction knowledge base (GRKB) to provide chemists with useful and well-organized knowledge. The method consists of three key steps: (1) the automatic recognition of reaction centers, (2) the definition of a hierarchy of reaction patterns, and (3) the organization of the generic reaction knowledge. Significant reaction knowledge has been discovered via mining a subset of the InfoChem Reaction database. A frame system has been constructed to store and retrieve the GRKB. Applications of this GRKB to synthesis planning are illustrated.

This work presents a new spectral data compression-rebuilding technique to translate the full IR spectral data into compact codes based on the analysis and comprehension encoding approach. This method has been successfully applied to a sample set of 505 IR spectra randomly picked from 100 000 spectra. The results show that the compression ratio reaches 12.7:1 under a very weak curve distortion. The choice of the number and shape of the basis functions is flexible. The IR spectra can be compressed in a fixed data size in fulfilling the distortion criteria. The data after compression have no significance in the sense of IR spectra. To recover the original spectra, a specific algorithm must be applied. So the method can be used as a cryptic tool. Furthermore, the method can be applied to the compression of other complex curve by utilizing some of proper basis functions.