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Cracks are often exposed to mixed mode I/II loading because of the random direction of crack relative to the external load, causing rock failure in rock engineering. However, many mixed mode I/II fracture properties of rock with different loading angles (β) are still poorly understood. To investigate the influence of β on mixed mode I/II fracture behavior, cracked straight through Brazilian disc tests were performed on sandstone under various β at the loading rate of 0.2 kN/s. The results show that the effect of β on the peak load and crack propagation velocity is slight. The mode I stress intensity factor (SIF) decreases from positive to negative with increasing β, while mode II SIF first increases and then decreases as β exceeds approximately 30°. The mixed mode I/II fracture toughness increases linearly with increasing β. When β exceeds 60°, the crack initiation location shifts from the center of the semi-circular notch tip to the surface of preset crack. For non-tip cracking, the crack propagates toward the loading point in a direction approximately perpendicular to the preset crack. The threshold β for it decreases with increasing internal friction coefficient and relative crack length. Moreover, the mixed-mode fracture surface becomes smoother as the mode I component contribution drops. There are remarkable differences in the prediction of fracture initiation angles and SIFs of various rock types applying the generalized maximum tangential stress criterion. The findings of this study could help understand the mixed mode I/II fracture observed in rock engineering.

Sea level rise (SLR) and heavy precipitation events are increasing the frequency and extent of coastal flooding, which can trigger releases of toxic chemicals from hazardous sites, many of which are in low-income communities of color. We used regression models to estimate the association between facility flood risk and social vulnerability indicators in low-lying block groups in California. We applied dasymetric mapping techniques to refine facility boundaries and population estimates and probabilistic SLR projections to estimate facilities' future flood risk. We estimate that 423 facilities are at risk of flooding in 2100 under a high emissions scenario (RCP 8.5). One unit standard deviation increases in nonvoters, poverty rate, renters, residents of color, and linguistically isolated households were associated with a 1.5-2.2 times higher odds of the presence of an at-risk site within 1 km (ORs [95% CIs]: 2.2 [1.8, 2.8], 1.9 [1.5, 2.3], 1.7 [1.4, 1.9], 1.5 [1.2, 1.9], and 1.5 [1.2, 1.9], respectively). Among block groups near at least one at-risk site, the number of sites increased with poverty, proportion of renters and residents of color, and lower voter turnout. These results underscore the need for further research and disaster planning that addresses the differential hazards and health risks of SLR.

To conduct a Food Literacy Evaluation Questionnaire Chinese Version (FLEQ-Ch) through a cross-cultural validation of the original questionnaire.This was an observational, cross-sectional study undertaken in two phases: (1) translation and cross-culture adaptation, and (2) psychometric evaluation.A total of 509 residents in Yangzhou City, China were enrolled in this study.A translation and cross-cultural adaptation of the FLEQ in Chinese was developed. The psychometric characteristics of FLEQ-Ch were analyzed for internal consistency, content validity, construct validity and discriminant validity.The KMO value of the questionnaire was 0.901 and the approximate chi-square value of Bartlett's sphericity test was 8132.538. The ranges of the Cronbach's α coefficient and the test-retest coefficient of the total questionnaire and three dimensions were 0.869-0.955 and 0.941-0.952, respectively. The value of content validity index of the total questionnaire was 0.945. Construct validity: (1) Aggregation coefficient was between 0.828 and 0.955; (2) Discrimination coefficient was between 0.004 and 0.227; (3) Correlation coefficient between each factor was between 0.046 and 0.188; the correlation coefficient between each factor and the total questionnaire ranged from 0.419 to 0.788. Discriminant validity: the standardized factor loadings of all items on the corresponding factors were 0.75-0.96. The results of the model-fit indices showed RMSEA was 0.08 and GFI was 0.91.The FLEQ-Ch can effectively evaluate the food literacy of the general public in terms of foods planning and management, foods selection, and foods-making attitudes. It covers the four areas of food literacy, and shows good practicability and operability.

Climate change and urbanization are rapidly increasing human exposure to extreme ambient temperatures, yet few studies have examined temperature and mortality in Latin America. We conducted a nonlinear, distributed-lag, longitudinal analysis of daily ambient temperatures and mortality among 326 Latin American cities between 2002 and 2015. We observed 15,431,532 deaths among ≈2.9 billion person-years of risk. The excess death fraction of total deaths was 0.67% (95% confidence interval (CI) 0.58–0.74%) for heat-related deaths and 5.09% (95% CI 4.64–5.47%) for cold-related deaths. The relative risk of death was 1.057 (95% CI 1.046–1.067%) per 1 °C higher temperature during extreme heat and 1.034 (95% CI 1.028–1.040%) per 1 °C lower temperature during extreme cold. In Latin American cities, a substantial proportion of deaths is attributable to nonoptimal ambient temperatures. Marginal increases in observed hot temperatures are associated with steep increases in mortality risk. These risks were strongest among older adults and for cardiovascular and respiratory deaths.

Jia Wei,1 Xiaofeng Lu,2 Qin Liu,1 Yao Fu,3 Song Liu,4 Lin Li,3 Fangcen Liu,3 Xiangshan Fan,3 Ju Yang,1 Yang Yang,1 Yang Zhao,5 Wenxian Guan,2 Baorui Liu1 1The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, 210008, People’s Republic of China; 2Department of General Surgery, Drum Tower Hospital, Nanjing, 210008, People’s Republic of China; 3Department of Pathology, Drum Tower Hospital, Nanjing, 210008, People’s Republic of China; 4Department of Radiology, Drum Tower Hospital, Nanjing, 210008, People’s Republic of China; 5Department of Biostatistics, Nanjing Medical University, Nanjing, 210029, People’s Republic of ChinaCorrespondence: Baorui Liu, The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, 210008, People’s Republic of China, Tel +86 2583107081, Email baoruiliu@nju.edu.cnPurpose: Concurrent chemoradiotherapy (cCRT) is the mainstay therapy of locally advanced gastric (G) and gastroesophageal junction (GEJ) cancers with a poor prognosis. Programmed cell death receptor-1 (PD-1) inhibitor has been approved and recommended to treat ≥ 3 line G/GEJ patients. A significant clinical benefit of PD-1 inhibitors in addition to cCRT has been observed in locally advanced lung cancer. Sintilimab, a humanized IgG4 monoclonal antibody with high affinity and specificity for PD-1, has shown promising efficacy with an overall response rate of 85% in combination with chemotherapy in gastric cancer in a phase Ib study (NCT02937116).Patients and Methods: SHARED is a prospective, multicentre, single-arm Phase II trial in China, exploring the efficacy of sintilimab in combination with cCRT in locally advanced G/GEJ adenocarcinoma. According to a Simon optimal two-stage clinical design, 34 patients will be enrolled. All the eligible patients will receive one cycle of induction chemotherapy (S-1 plus nab-PTX) combined with sintilimab, followed by cCRT (radiotherapy plus nab-PTX) combined with sintilimab. Prior to the surgery, patients will receive another cycle of chemotherapy (S-1 plus nab-PTX) combined with sintilimab. In the adjuvant setting, all participants will be treated with 3 cycles of chemotherapy (S-1 plus nab-PTX) combined with sintilimab. The primary endpoint is the rate of pathological complete response (pCR). The secondary endpoints include disease-free survival (DFS), major pathological response (MPR), R0 resection rate, surgical AEs, overall survival (OS), event-free survival (EFS), and safety profile. Moreover, the prognostic value of tumor biomarkers and immune biomarkers will be explored.Conclusion: SHARED is designed to primally evaluate the efficacy and safety of sintilimab in combination with cCRT in locally advanced G/GEJ cancers and to prospectively validate the prognostic value of tumor biomarkers and immune biomarkers.Keywords: anti-PD-1, induction chemotherapy, chemoradiotherapy, immunotherapy

Air leakage caused by mining-induced fractures around the borehole and roadway greatly affects the effect of underground gas drainage. Therefore, the study of the air leakage model considering three-dimensional stress and coal elastic-plastic deformation is of great significance to prevent air leakage. In this work, a model of air leakage outside borehole in mining-disturbed coal seam including a fully coupled gas-air flow and coal mechanics model and a mining-induced damage permeability model was developed and verified. The model was used to study the gas-air migration law and air leakage mechanism during gas drainage, and the influence of key parameters including initial permeability and sealing depth on gas drainage effect was analyzed. The results show: (1) The model can be used to characterize the air leakage of pre-drainage boreholes in mining-disturbed coal seams. (2) The gas and air pressure in the severe mining disturbance area rapidly decreased and increased in a short time. (3) Increasing the initial permeability and sealing depth will promote the gas flow in the borehole in the early stage, but the gas concentration will be reduced. The research results provide a scientific theoretical basis for improving the gas drainage effect and ensuring mining safety.

Bone age assessment (BAA) from hand radiographs is crucial for diagnosing endocrinology disorders in adolescents and supplying therapeutic investigation. In practice, due to the conventional clinical assessment being a subjective estimation, the accuracy of BAA relies highly on the pediatrician's professionalism and experience. Recently, many deep learning methods have been proposed for the automatic estimation of bone age and had good results. However, these methods do not exploit sufficient discriminative information or require additional manual annotations of critical bone regions that are important biological identifiers in skeletal maturity, which may restrict the clinical application of these approaches. In this research, we propose a novel two-stage deep learning method for BAA without any manual region annotation, which consists of a cascaded critical bone region extraction network and a gender-assisted bone age estimation network. First, the cascaded critical bone region extraction network automatically and sequentially locates two discriminative bone regions via the visual heat maps. Second, in order to obtain an accurate BAA, the extracted critical bone regions are fed into the gender-assisted bone age estimation network. The results showed that the proposed method achieved a mean absolute error (MAE) of 5.45 months on the public dataset Radiological Society of North America (RSNA) and 3.34 months on our private dataset.

Hibiscus hamabo and Paliurus ramosissimus are Korea’s endangered flora species, are predominantly native to Jeju Island, with more limited native appearances on few of Korea’s southern islands. The differences between the northernmost area (Jeju) and Japan’s southwestern native habitat characteristics of H. hamabo and P. ramosissimus were investigated utilizing a B-B method. In the case of semi-mangrove plants on Jeju island, its native habitats are divided into the inlet and gulf areas. Over time as silt soil deposits took shape, Cnidium japonicum and Limonium tetragonum appeared along with H. hamabo in bay areas, while Vitex rotundifolia and Eurya emarginata appeared at bedrock sites that had poor soil conditions in gulf areas. P. ramosissimus appeared in three habitats: wetland type, seashore rock type, and costal roadside type. In wetland type, Cyclosorus interruptus and Persicaria japonica appeared with high contributions. In the seashore rock type, the woody and vines native to the coast, the Euonymus japonicus and the Lonicera japonica, are found. In the ruderal site beside the coastal road, Humulus scandens, Rosa multiiflora, and other annual plants appeared. Jeju’s habitat appeared to have a more limited natural propagation radius than found in Japan, and are vulnerable to damage by coastal development. Therefore, more preservations efforts are essential of H. hamabo and P. ramosissimus, which support the integrity of coastal ecosystems and contributes to carbon capture.

Individual tree structure mapping in cities is important for urban environmental studies. Despite mapping products for tree canopy cover and biomass are reported at multiple spatial scales using various approaches, spatially explicit mapping of individual trees and their three-dimensional structure is sparse. Here we produced an individual tree dataset including tree locations, height, crown area, crown volume, and biomass over the entire New York City, USA for 6,005,690 trees. Individual trees were detected and mapped from remotely sensed datasets along with their height and crown size information. Tree biomass in 296 field plots was measured and modelled using i-Tree Eco. Wall-to-wall tree biomass was mapped using relationships between field measurements and remotely sensed datasets and downscaled to individual trees. Validation using field-plot measurements indicated that our mapping products overestimated tree number, mean tree height and maximum tree height by 11.1%, 8.6%, and 5.3%, respectively. These overestimations were mainly due to the spatial and temporal mis-match between field measurements and remote sensing observations and uncertainties in tree segmentation algorithms. This dataset enables the evaluation of urban forest ecosystem services including regulating urban heat and promoting urban health, which can provide valuable insights for urban forest management and policy making.

Underground hydrogen storage (UHS) is a key strategy in the implementation of a large-scale hydrogen (H2) economy and promotion of renewable energy development/utilization. For UHS in water-wet saline aquifers, H2 displaces in-situ brine during injection; during well shut-in and H2 withdrawal, brine imbibes back into the flow paths where it displaces some H2. These processes are influenced by H2-brine transport physics, H2-brine-rock interactions and injection/withdrawal schemes, which, in turn, determine H2 storage capacities and injection/withdrawal efficiency. However, these effects are poorly understood. Therefore, this work focuses on the impact of relative permeability hysteresis (RPH), wettability, and H2 withdrawal rate on UHS performance in a saline aquifer. Furthermore, differences between UHS and CO2 geo-storage (CGS) are examined. The primary findings include: 1) RPH results in a smaller H2 withdrawal factor (H2-WF), but a larger H2 withdrawal purity (H2-WP); 2) H2-WF increases with rock hydrophobicity, while H2-WP is mostly insensitive to rock wettability; 3) under similar storage conditions, H2-WF and H2-WP are approximately 10% less than CO2-WF and CO2-WP. These insights demonstrate the significance of RPH and rock wettability on UHS performance and provides guidance on H2 injection/withdrawal scheme optimization. This study aids in the implementation of an industry-scale hydrogen economy.

With the continuous development of neural networks for computer vision tasks, more and more network architectures have achieved outstanding success. As one of the most advanced neural network architectures, DenseNet shortcuts all feature maps to solve the model depth problem. Although this network architecture has excellent accuracy with low parameters, it requires an excessive inference time. To solve this problem, HarDNet reduces the connections between the feature maps, making the remaining connections resemble harmonic waves. However, this compression method may result in a decrease in the model accuracy and an increase in the parameters and model size. This network architecture may reduce the memory access time, but its overall performance can still be improved. Therefore, we propose a new network architecture, ThreshNet, using a threshold mechanism to further optimize the connection method. Different numbers of connections for different convolution layers are discarded to accelerate the inference of the network. The proposed network has been evaluated with image classification using CIFAR 10 and SVHN datasets under platforms of NVIDIA RTX 3050 and Raspberry Pi 4. The experimental results show that, compared with HarDNet68, GhostNet, MobileNetV2, ShuffleNet, and EfficientNet, the inference time of the proposed ThreshNet79 is 5%, 9%, 10%, 18%, and 20% faster, respectively. The number of parameters of ThreshNet95 is 55% less than that of HarDNet85. The new model compression and model acceleration methods can speed up the inference time, enabling network models to operate on mobile devices., IEEE Access

Hepatocellular carcinoma (HCC) is among the leading causes of cancer incidence and death. Despite decades of research and development of new treatment options, the overall outcomes of patients with HCC continue to remain poor. There are areas of unmet need in risk prediction, early diagnosis, accurate prognostication, and individualized treatments for patients with HCC. Recent years have seen an explosive growth in the application of artificial intelligence (AI) technology in medical research, with the field of HCC being no exception. Among the various AI-based machine learning algorithms, deep learning algorithms are considered state-of-the-art techniques for handling and processing complex multimodal data ranging from routine clinical variables to high-resolution medical images. This article will provide a comprehensive review of the recently published studies that have applied deep learning for risk prediction, diagnosis, prognostication, and treatment planning for patients with HCC.

As shallow resources are increasingly depleted, the mechanics’ theory and testing technology of deep in-situ rock has become urgent. Traditional coring technologies obtain rock samples without retaining the in-situ environmental conditions, leading to distortion of the measured parameters. Herein, a coring and testing systems retaining in-situ geological conditions is presented: the coring system that obtains in-situ rock samples, and the transfer and testing system that stores and analyzes the rocks under a reconstructed environment. The ICP-Coring system mainly consists of the pressure controller, active insulated core reactor and insulation layer and sealing film. The ultimate bearing strength of 100 MPa for pressure-preservation, temperature control accuracy of 0.97% for temperature-retained are realized. CH4 and CO permeability of the optimized sealing film are as low as 3.85 and 0.33 ppm/min. The average tensile elongation of the film is 152.4% and the light transmittance is reduced to 0%. Additionally, the pressure and steady-state temperature accuracy for reconstructing the in-situ environment of transfer and storage system up to 1% and ±0.2 is achieved. The error recorded of the noncontact sensor ring made of low-density polymer is less than 6% than that of the contact test. The system can provide technical support for the deep in-situ rock mechanics research, improving deep resource acquisition capabilities and further clarifying deep-earth processes.

Efficient, safe, and environmentally friendly methods for the low-carbon utilization of coal are required to exploit this resource as a source of cleaner energy. Tar-rich coal can produce a high volume of oil and is abundant in western China. Currently, tar-rich coal is mostly combusted for power generation, which results in wastage of valuable oil resources and serious environmental pollution. Researchers have focused on achieving zero or near-zero carbon emissions while alleviating damage and pollution to geological formations when mining coal resources. In particular, the use of an intelligent unmanned automatic mining machine (UAMM) integrating microwave pyrolysis technology for the in situ mining and conversion of coal into oil and gas has been proposed. However, to date, studies on the microwave pyrolysis of tar-rich coal for the efficient extraction of oil are lacking. In this study, we outline the state-of-the-art developments in the microwave treatments of coal. The principles and advantages of microwave heating compared with traditional heating methods are discussed. Further, current research and applications of microwave-assisted coal processing are reviewed. We also discuss the challenges and future developments in the field of the microwave-based pyrolysis of coal. This report provides a reference for the application of microwave technology to in situ mining, pyrolysis, and conversion of tar-rich coal into liquid energy resources based on a UAMM.

The precision synthesis of helical bilayer nanographenes (NGs) with new topology is of substantial interest because of their exotic physicochemical properties. However, helical bilayer NGs bearing non-hexagonal rings remain synthetically challenging. Here we present the efficient synthesis of the first helical bilayer nonbenzenoid nanographene (HBNG1) from a tailor-made azulene-embedded precursor, which contains a novel [10]helicene backbone with two embedded heptagons. Single-crystal X-ray analysis reveals its highly twisted bilayer geometry with a record small interlayer distance of 3.2 Å among the reported helical bilayer NGs. Notably, the close interlayer distance between the two layers offers intramolecular through-space conjugation as revealed by in situ spectroelectrochemistry studies together with DFT simulations. Furthermore, the chiroptical properties of the P/M enantiomers of HBNG1 are also evaluated by circular dichroism and circularly polarized luminescence.

Transparent physical models of real rocks fabricated using three-dimensional (3D) printing technology are used in photoelastic experiments to quantify the evolution of the internal stress and deformation fields of rocks. Therefore, they are rendered as an emerging powerful technique to quantitatively reveal the intrinsic mechanisms of rock failure. The mechanical behavior of natural rocks exhibits a significant size effect; however, limited research has been conducted on whether transparent physical models observe similar size effects. In this study, to make the transparent printed models accurately demonstrate the mechanical behavior of natural rocks and reveal the internal mechanism of the size effect in rock mechanical behavior, the size effect in 3D printed models of fractured and porous rocks under uniaxial compressive loading was investigated. Transparent cylindrical models with different sizes that contained different fractured and porous structures were printed using the fracture and porous characteristics extracted from natural coal and sandstone. The variation in uniaxial compressive strength and elastic modulus of fractured and porous models for increasing model sizes were obtained through uniaxial compression experiments. Finally, the influence of internal discontinuous structural features, such as fractures and pores, on the size effect pertaining to the mechanical behavior of the model was analyzed and elaborated by comparing it with the mechanical properties of the continuous homogeneous model without fractures and pores. The findings provided support and reference to analyze the size effect of rock mechanical behavior and the effect of the internal discontinuous structure using 3D printed transparent models.

Whether oil emplacement and diagenetic sequences provoke, deteriorate, or have no effect on pore network evolution, as implied by recent tests and theoretical analysis, are critical factors in forecasting hydrocarbon exploration and development potentials. Therefore, a systematic investigation on the effect of oil emplacement of tight sandstones is conducted to study the importance of this behavior on the pore evolution path. This study evaluated the role played by oil emplacement and diagenesis in the pore network evolution of Upper Triassic tight sandstones in the Ordos Basin. To help provide a comprehensive understanding, we have used a multidisciplinary method including physical properties, casting thin section, scanning electron microscope, X-ray diffraction, fluorometric, and inclusion analysis. The results demonstrate that the sandstones could be divided into four groups based on new criteria: calcareous sandstone, high soft component sandstone, low soft component sandstone with continual oil emplacement, and low soft component sandstone with intermittent oil emplacement. The physical properties of those types of sandstones were gradually reduced. Quartz cement captured hydrocarbon, carbonate captured hydrocarbon, free hydrocarbon, and adsorbed hydrocarbon were the four main kinds of hydrocarbons. The maturity of those sandstones was decreased progressively, indicating that the formation time of those hydrocarbons was favorable to maturity. Four stages of oil emplacement happened, and large-scale emplacement mainly occurred in the late Jurassic and early Craterous. The evidence demonstrated that tight sandstones’ high porosity could be attributed to positive diagenetic contributions with a complex interplay of chemical compaction, early formed clays, and large-scale oil emplacement. This work would provide new sights for a better understanding of the tight oil accumulation modes, and the findings could be applied in the hydrocarbon exploration and development field.

In this study, the Liu–Murakami (LM) creep damage-coupled model was considered to evaluate the creep properties of martensitic stainless steel. The degree of creep damage was examined at two temperatures (565 ℃ and 593 ℃) to assess mechanically and thermally activated processes. A series of high applied stresses (applied stress/ultimate strength > 0.5) was considered for accelerated creep loadings. A full set of creep constants was determined by combining the Norton and LM models. Constitutive equations were used to quantitatively estimate experimental creep curves. The variation in creep constants was discussed based on stress sensitivity, such as stress triaxiality and applied stress, depending on the power of stress. The creep strain–time curves were successfully estimated. The comparison between the experimental and analytical results was in good agreement in the tertiary regime. In addition, the compensation of the two applied temperatures provides a supplementary explanation of the relationship between the ultimate strength and rupture time in terms of temperature sensitivity. The analytical results show that different applied stresses and temperatures could be compensated to characterize the creep behavior of the material. Thus, the creep strain–time and creep strain rate–certain rupture time curves were finally achieved. The analytical process in this study provides a laboratory-scale assessment of creep properties using the accelerated creep test and LM model.

BackgroundPancreatic ductal adenocarcinoma (PDAC) is a fatal malignancy with a low resection rate. Chemotherapy and radiotherapy (RT) are the main treatment approaches for patients with advanced pancreatic cancer, and neoadjuvant chemoradiotherapy is considered a promising strategy to increase the resection rate. Recently, immune checkpoint inhibitor (ICI) therapy has shown remarkable efficacy in several cancers. Therefore, the combination of ICI, chemotherapy, and concurrent radiotherapy is promising for patients with potentially resectable pancreatic cancer, mainly referring to locally advanced (LAPC) and borderline resectable pancreatic cancer (BRPC), to increase the chances of conversion to surgical resectability and prolong survival. This study aims to introduce the design of a clinical trial.MethodsThis is an open-label, single-arm, and single-center phase II trial. Patients with pathologically and radiographically confirmed LAPC or BRPC without prior anti-cancer treatment or severe morbidities will be enrolled. All patients will receive induction therapy and will be further evaluated by the Multiple Disciplinary Team (MDT) for the possibility of surgery. The induction therapy consists of up to four cycles of gemcitabine 1,000 mg/m2 and nab-paclitaxel 125 mg/m2via intravenous (IV) infusion on days 1 and 8, along with tislelizumab (a PD-1 monoclonal antibody) 200 mg administered through IV infusion on day 1 every 3 weeks, concurrently with stereotactic body radiation therapy (SBRT) during the third cycle of treatment. After surgery, patients without progression will receive another two to four cycles of adjuvant therapy with gemcitabine, nab-paclitaxel, and tislelizumab. The primary objectives are objective response rate (ORR) and the R0 resection rate. The secondary objectives are median overall survival (mOS), median progression free survival (mPFS), disease control rate (DCR), pathological grade of tumor tissue after therapy, and adverse reactions. Besides, we expect to explore the value of circulating tumor DNA (ctDNA) in predicting tumor response to induction therapy and survival outcome of patients.DiscussionThis is a protocol for a clinical trial that attempts to evaluate the safety and efficacy of the combination of anti-PD-1 antibody plus chemotherapy and radiotherapy as the induction therapy for LAPC and BRPC. The results of this phase II study will provide evidence for the clinical practice of this modality.Clinical Trial Registrationhttp://www.chictr.org.cn/edit.aspx?pid=53720&htm=4, identifier ChiCTR2000032955.

Nanographenes are inclined to assemble into stacked columnar structures that are stabilized by π-π interactions, whereas other supramolecular structures of nanographenes, such as prisms and cages, are rarely investigated. Herein, a diazananographene was synthesized, and then assembled with a coordination unit, thereby producing a triangular metallaprism. After adding C

Background: Accumulating evidence has revealed the important role of Cancer Stem Cells (CSCs) in driving tumor initiation and tumor relapse or metastasis. Therapeutic strategies that selectively target CSCs may be effective approaches to eliminate cancer. Salinomycin, an antitumor agent, was identified as a selective inhibitor of several types of CSCs. We previously reported that salinomycin inhibits the migration and invasiveness of Liver Cancer Stem Cells (LCSCs). Objective: This study was conducted to explore the role of salinomycin in suppressing the stemness properties of LCSCs and the mechanism. Methods: LCSCs were identified and enriched from MHCC97H cells. Salinomycin was used to treat LCSCs at the indicated concentrations. Sphere formation ability, chemotherapy resistance, expression of CSC surface markers, Young’s modulus and tumorigenicity of LCSCs were assessed to evaluate the effect of salionmycin on LCSCs. The expression of β-catenin was evaluated by western blotting. LiCl was used to activate the Wnt/β-catenin signaling pathway. Results: Salinomycin suppresses the stemness properties of LCSCs. Moreover, salinomycin could also inhibit the activation of Wnt/β-catenin signaling in LCSCs. Nevertheless, the stemness properties of LCSCs could be recovered when Wnt/β-catenin signaling was activated by LiCl. Further studies demonstrated that salinomycin also significantly reduces the tumorigenicity of LCSCs in vivo by suppressing the Wnt/β-catenin signaling pathway. Conclusion: Salinomycin could suppress stemness properties and induce differentiation of LCSCs through the Wnt/β-catenin signaling pathway, which provides evidence that salinomycin may serve as a potential drug for liver cancer therapy targeting LCSCs in the clinic.

BACKGROUND Consideration of the huge burden both of tuberculosis (TB) and diabetes mellitus (DM) in China as a major public health issue, research focused on the relationship between DM and TB was needed. METHODS An observational study was conducted (2015-2018) in regional representative TB and lung disease hospitals in China. All the adult patients newly diagnosed of pulmonary TB were consecutively recruited in this study. RESULTS A total of 1417 patients newly diagnosed pulmonary TB was recruited in this research, 312 (22.02%) of them had the history of type 2 DM. Majority of patients were with fatigue, loss of weight and mild anaemia in TB-DM group compared with TB-NDM group (58.3% vs 47.5%, p = .001; 8.21 ± 6.2 vs 5.74 ± 4.0 kg, p