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The pore-fracture structure of deep coal reservoir is of great significance to the evaluation and exploration of deep coalbed methane resource potential. this work takes the 5 coal and rock samples from the DJ57 Benxi Formation in Daning-Jixian Block, east margin of Ordos Basin are selected as the research object. On the basis of coal rock and coal quality parameter testing, gas adsorption method, high pressure mercury injection method and micron CT scanning and other testing methods are adopted to conduct full-scale quantitative characterization of nano-scale pore and micron scale cracks in the pore and fissure structure of coal reservoir, and comprehensively evaluate the pore and fissure structure characteristics of different scales. Combined with permeability and methane isothermal adsorption experiments, the influence of micro-porosity and fissure on the occurrence and migration of coalbed methane in deep coal reservoirs was discussed. The results show that the multi-scale quantitative characterization of deep coal reservoir pores and fractures is based on a variety of pore characterization methods, and the pore and fracture volume distribution type is mainly U-shaped, showing a bimodal coexistence of micro-pores and micro-fractures, mainly concentrated in in 0.3-1.5 nm and > 100 μm. Among them, micropores (10 μm) accounted for 80.18%,6.70%,1.65% and 11.47% of the total pore crack volume, respectively. With the development of micropores, the adsorbed gas tends to increase, and micropores can provide a large number of adsorption sites for deep coalbed methane adsorption and occurrence. With the development of micro-fractures, the free gas volume tends to increase. Micro-fractures can provide a large amount of storage space and provide space conditions for deep coalbed methane enrichment. In addition, microcracks are interconnected in three-dimensional space, forming a network structure with strong connectivity. With the development of micro-fractures, the permeability of coal reservoir increases, and micro-fractures enhance the seepage capacity of coalbed methane. The adsorption capacity and development potential of deep coalbed methane are controlled by the development characteristics of nano-scale pores and micro-scale fractures respectively.

Abstract Background Due to the essential role of calcium in vital biological functions, diet low in calcium (DLC) is associated with various diseases. However, there is a lack of study about the current prevalence and health burden due to DLC using reliable data sources. Methods We used data from the Global Burden of Disease study 2019 (GBD 2019) to estimate the prevalence and health burden of DLC in 204 countries from 1990 to 2019, by age, sex, and sociodemographic index (SDI). The estimates were produced in DisMod-MR 2.1, a Bayesian meta-regression tool. Summary exposure value (SEV) was used to show the prevalence of DLC, while diseases adjusted life year (DALY) was used to represent the disease burden. The disease burden was estimated for DLC-induced colorectal cancer. Spearman Rank Order correlation was used for correlation analysis, and estimated annual percentage (EAPC) was used to reflect the temporal trends. Results From 1990 to 2019, the global prevalence of DLC decreased (EAPC of SEV, −0.47; 95% CI, −0.5 to −0.43), but have increased in Oceania region and in many countries, such as United Arab Emirates, New Zealand, Japan, and France. The global DALYs associated with low in calcium were estimated to be 3.14 million (95% uncertainty interval (UI), 2.25–4.26 million) in 2019, with an age standardized rate of 38.2 (95% UI, 27.2–51.8) per 100,000. Unlike the prevalence, the global age standardized DALY rates has remained unchanged (EAPC, −0.03; 95% CI, −0.12 to 0.07), but has increased in over 80 of the 204 countries, located mainly in Asia, Africa, and South America. In all years and regions, the age standardized SEV and DALY rates were higher in male people than that in female people. The prevalence (rho = −0.823; P

Abstract Background Danggui Sini decoction (DSD), a traditional Chinese medicine formula, has the function of nourishing blood, warming meridians, and unblocking collaterals. Our clinical and animal studies had shown that DSD can effectively protect against oxaliplatin (OXA)-induced peripheral neuropathy (OIPN), but the detailed mechanisms remain uncertain. Multiple studies have confirmed that gut microbiota plays a crucial role in the development of OIPN. In this study, the potential mechanism of protective effect of DSD against OIPN by regulating gut microbiota was investigated. Methods The neuroprotective effects of DSD against OIPN were examined on a rat model of OIPN by determining mechanical allodynia, biological features of dorsal root ganglia (DRG) as well as proinflammatory indicators. Gut microbiota dysbiosis was characterized using 16S rDNA gene sequencing and metabolism disorders were evaluated using untargeted and targeted metabolomics. Moreover the gut microbiota mediated mechanisms were validated by antibiotic intervention and fecal microbiota transplantation. Results DSD treatment significantly alleviated OIPN symptoms by relieving mechanical allodynia, preserving DRG integrity and reducing proinflammatory indicators lipopolysaccharide (LPS), IL-6 and TNF-α. Besides, DSD restored OXA induced intestinal barrier disruption, gut microbiota dysbiosis as well as systemic metabolic disorders. Correlation analysis revealed that DSD increased bacterial genera such as Faecalibaculum, Allobaculum, Dubosiella and Rhodospirillales_unclassified were closely associated with neuroinflammation related metabolites, including positively with short-chain fatty acids (SCFAs) and sphingomyelin (d18:1/16:0), and negatively with pi-methylimidazoleacetic acid, l-glutamine and homovanillic acid. Meanwhile, antibiotic intervention apparently relieved OIPN symptoms. Furthermore, fecal microbiota transplantation further confirmed the mediated effects of gut microbiota. Conclusion DSD alleviates OIPN by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.

Abstract To evaluate the current incidence of pulmonary hemorrhage and the potential factors contributing to its increased risk after percutaneous CT-guided pulmonary nodule biopsy and to summarize the technical recommendations for its treatment. In this observational study, patient data were collected from ten medical centers from April 2021 to April 2022. The incidence of pulmonary hemorrhage was as follows: grade 0, 36.1% (214/593); grade 1, 36.8% (218/593); grade 2, 18.9% (112/593); grade 3, 3.5% (21/593); and grade 4, 4.7% (28/593). High-grade hemorrhage (HGH) occurred in 27.2% (161/593) of the patients. The use of preoperative breathing exercises (PBE, p =0.000), semiautomatic cutting needles (SCN, p = 0.004), immediate contrast enhancement (ICE, p =0.021), and the coaxial technique (CoT, p = 0.000) were found to be protective factors for HGH. A greater length of puncture (p =0.021), the presence of hilar nodules (p = 0.001), the presence of intermediate nodules (p = 0.026), a main pulmonary artery diameter (mPAD) larger than 29 mm (p = 0.015), and a small nodule size (p = 0.014) were risk factors for high-grade hemorrhage. The area under the curve (AUC) was 0.783. These findings contribute to a deeper understanding of the risks associated with percutaneous CT-guided pulmonary nodule biopsy and provide valuable insights for developing strategies to minimize pulmonary hemorrhage.

Abstract Electrostatic generators show great potential for powering widely distributed electronic devices in Internet of Things (IoT) applications. However, a critical issue limiting such generators is their high impedance mismatch when coupled to electronics, which results in very low energy utilization efficiency. Here, we present a high-performance energy management unit (EMU) based on a spark-switch tube and a buck converter with an RF inductor. By optimizing the elements and parameters of the EMU, a maximum direct current output power of 79.2 mW m-2 rps-1 was reached for a rotary electret generator with the EMU, achieving 1.2 times greater power output than without the EMU. Furthermore, the maximum power of the contact-separated triboelectric nanogenerator with an EMU is 1.5 times that without the EMU. This excellent performance is attributed to the various optimizations, including utilizing an ultralow-loss spark-switch tube with a proper breakdown voltage, adding a matched input capacitor to enhance available charge, and incorporating an RF inductor to facilitate the high-speed energy transfer process. Based on this extremely efficient EMU, a compact self-powered wireless temperature sensor node was demonstrated to acquire and transmit data every 3.5 s under a slight wind speed of 0.5 m/s. This work greatly promotes the utilization of electrostatic nanogenerators in practical applications, particularly in IoT nodes.

Abstract Solar panels often suffer from dust accumulation, significantly reducing their output, especially in desert regions where many of the world's largest solar plants are located. Here, an autonomous dust removal system for solar panels, powered by a wind‐driven rotary electret generator is proposed. The generator applies a high voltage between one solar panel's output electrode and an upper mesh electrode to generate a strong electrostatic field. It is discovered that dust particles on the insulative glass cover of the panel can be charged under the high electrical field, assisted by adsorbed water, even in low‐humidity environments. The charged particles are subsequently repelled from the solar panel with the significant Coulomb force. Two panels covered with sand dust are cleaned in only 6.6 min by a 15 cm diameter rotary electret generator at 1.6 m s−1 wind speed. Experimental results manifest that the system can work effectively in a wide range of environmental conditions, and doesn't impact the panel performance for long‐term operation. This autonomous system, with its high dust removal efficiency, simplicity, and low cost, holds great potential in practical applications.

Gentiana szechenyii Kanitz. and Gentiana veitchiorum Hemsl. are two wild medicinal plants widely used in Tibetan medicine. In recent decades, their wild populations have declined rapidly due to persistent over-harvesting of their flowers. Because their flowers are small and dense, it is difficult to rely on manual counting under wild conditions. The combination of deep learning and unmanned aerial vehicle remote sensing (UAVRS) is a new method for plant surveys. We trained 12 of the most advanced or widely used YOLO models on a custom dataset to achieve quantitative detection of both plant flowers in UAVRS images. The accuracy, precision and recall of G. szechenyii Flower (GSF) detection can reach 97.00%, 90.40% and 95.40%, respectively (based on YOLOv7). Similarly, those of G. veitchiorum Flower (GVF) detection can reach 93.40%, 91.30% and 90.60%, respectively (based on YOLOv5n), and the highest mAP can reach 94.90% (based on YOLOv5m). Based on the detection results, it is calculated that the total yield of dried GSF and GVF that can be harvested as medicinal materials in study area ranges from 1.88 to 2.10 g·m−2 and 4.42–4.62 g·m−2, respectively. The results show that deep learning and UAVRS can be used for quantitative detection of GSF and GVF, which is helpful for further research and protection of these two plants.

Abstract Post-embolization syndrome (PES) is a frequent complication after receiving transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC), but only a few studies have focused on the factors influencing PES in those patients. In this study, the impact factors of PES were explored and a nomogram was constructed to predict the occurrence of PES in HCC patients with TACE. This was a retrospective cohort study of HCC patients who underwent TACE obtained from the third affiliated Hospital of Kunming Medical University between January 1, 2020, and September 1, 2022. T‑test and Chi‑square test were used to search for factors influencing PES occurrence, and then the nomogram was further established based on multivariable logistic regression analysis. Validation of the predictive nomogram was also evaluated by calibration curve, concordance index (C-index), and receiver operating characteristic (ROC) curves. The enrolled patients (n = 258) were randomly assigned to the primary cohort (n = 180) and validation cohort (n = 78) in a 7:3 ratio. Among 180 patients in the primary cohort, 106 (58.89%) experienced PES. TACE types (P = 0.015), embolization degree (P = 0.008), and tumor number (P = 0.026) were identified as predictors by the logistic regression analysis and were used to develop the predictive nomogram. The internally validated and externally validated C-indexes were 0.713 and 0.703, respectively. The calibration curves presented good consistency between actual and predictive survival. Types of embolic agents, embolization degree, and tumor number were found to be the predictors of PES after TACE. The nomogram could reliably predict PES in HCC patients with TACE. This predictive model might be considered for clinical practice.

Abstract Pneumonia is a highly lethal disease, and research on its treatment and early screening tools has received extensive attention from researchers. Due to the maturity and cost reduction of chest X-ray technology, and with the development of artificial intelligence technology, pneumonia identification based on deep learning and chest X-ray has attracted attention from all over the world. Although the feature extraction capability of deep learning is strong, existing deep learning object detection frameworks are based on pre-defined anchors, which require a lot of tuning and experience to guarantee their excellent results in the face of new applications or data. To avoid the influence of anchor settings in pneumonia detection, this paper proposes an anchor-free object detection framework and RSNA dataset based on pneumonia detection. First, a data enhancement scheme is used to preprocess the chest X-ray images; second, an anchor-free object detection framework is used for pneumonia detection, which contains a feature pyramid, two-branch detection head, and focal loss. The average precision of 51.5 obtained by Intersection over Union (IoU) calculation shows that the pneumonia detection results obtained in this paper can surpass the existing classical object detection framework, providing an idea for future research and exploration.

Abstract In face-to-face communication, multimodal cues such as prosody, gestures, and mouth movements can play a crucial role in language processing. While several studies have addressed how these cues contribute to native (L1) language processing, their impact on non-native (L2) comprehension is largely unknown. Comprehension of naturalistic language by L2 comprehenders may be supported by the presence of (at least some) multimodal cues, as these provide correlated and convergent information that may aid linguistic processing. However, it is also the case that multimodal cues may be less used by L2 comprehenders because linguistic processing is more demanding than for L1 comprehenders, leaving more limited resources for the processing of multimodal cues. In this study, we investigated how L2 comprehenders use multimodal cues in naturalistic stimuli (while participants watched videos of a speaker), as measured by electrophysiological responses (N400) to words, and whether there are differences between L1 and L2 comprehenders. We found that prosody, gestures, and informative mouth movements each reduced the N400 in L2, indexing easier comprehension. Nevertheless, L2 participants showed weaker effects for each cue compared to L1 comprehenders, with the exception of meaningful gestures and informative mouth movements. These results show that L2 comprehenders focus on specific multimodal cues – meaningful gestures that support meaningful interpretation and mouth movements that enhance the acoustic signal – while using multimodal cues to a lesser extent than L1 comprehenders overall.

Abstract To better characterize the heterogeneity of transitional shale pore structure and understand its impact on shale gas enrichment, fine characterization of the pore structure of different shale lithofacies was performed by field‐emission scanning electron microscopy, high‐pressure mercury injection, low‐temperature N2 adsorption, and low‐pressure CO2 adsorption. Fractal theory was used to obtain the fractal dimension of the shale pores at different scales and reveal the relationships among the pore structural characteristics, mineral composition, total organic carbon content, and fractal dimension of the shale and their geological significance. The results showed that organic pores, intergranular pores, intragranular pores, and microcracks were generally developed in the transitional shale samples from the study area; elliptic or irregular organic pores were mainly developed in the argillaceous shale lithofacies and siliceous shale lithofacies, and wedge‐shaped or irregular intragranular pores were mainly developed in the calcareous shale lithofacies. The pore size distribution showed a multipeak pattern, and mesopores were the main contributors to the total pore volume (PV), while micropores and macropores contributed little to the total PV. The PV and specific surface area of the siliceous shale were lower than those of the argillaceous shale but higher than those of the calcareous shale, indicating that the change in lithofacies had a significant effect on the shale pores. The common influence of clay minerals, quartz content, and total organic carbon content results in strong heterogeneity and complex pore structure characteristics of shale reservoirs. The pores in the transitional shale from the study area had obvious multiscale fractal characteristics, and the fractal dimension characteristics of different lithofacies and pores at different scales were different, which reflected that the pore structure of the shale had strong heterogeneity. The heterogeneity of the shale pores mainly originated from the macropores and mesopores, while the heterogeneity of micropores was relatively low. The heterogeneity of the pore development and structure at different scales was controlled by the mineral composition matter and organic matter abundance to varying degrees.

Abstract Objects Colorectal cancer (CRC) is one of the most common cancers in the world. Approximately two-thirds of patients with CRC will develop colorectal cancer liver metastases (CRLM) at some point in time. In this study, we aimed to construct a prognostic model of CRLM and its competing endogenous RNA (ceRNA) network. Methods RNA-seq of CRC, CRLM and normal samples were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database. Limma was used to obtain differential expression genes (DEGs) between CRLM and CRC from sequencing data and GSE22834, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses were performed, respectively. Univariate Cox regression analysis and lasso Cox regression models were performed to screen prognostic gene features and construct prognostic models. Functional enrichment, estimation of stromal and immune cells in malignant tumor tissues using expression data (ESTIMATE) algorithm, single-sample gene set enrichment analysis, and ceRNA network construction were applied to explore potential mechanisms. Results An 8-gene prognostic model was constructed by screening 112 DEGs from TCGA and GSE22834. CRC patients in the TCGA and GSE29621 cohorts were stratified into either a high-risk group or a low-risk group. Patients with CRC in the high-risk group had a significantly poorer prognosis compared to in the low-risk group. The risk score was identified as an independent predictor of prognosis. Functional analysis revealed that the risk score was closly correlated with various immune cells and immune-related signaling pathways. And a prognostic gene-associated ceRNA network was constructed that obtained 3 prognosis gene, 14 microRNAs (miRNAs) and 7 long noncoding RNAs (lncRNAs). Conclusions In conclusion, a prognostic model for CRLM identification was proposed, which could independently identify high-risk patients with low survival, suggesting a relationship between local immune status and prognosis of CRLM. Moreover, the key prognostic genes-related ceRNA network were established for the CRC investigation. Based on the differentially expressed genes between CRLM and CRC, the prognosis model of CRC patients was constructed.

Abstract Background The objective response rate of microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) patients with first-line anti-programmed cell death protein-1 (PD-1) monotherapy is only 40–45%. Single-cell RNA sequencing (scRNA-seq) enables unbiased analysis of the full variety of cells comprising the tumor microenvironment. Thus, we used scRNA-seq to assess differences among microenvironment components between therapy-resistant and therapy-sensitive groups in MSI-H/mismatch repair-deficient (dMMR) mCRC. Resistance-related cell types and genes identified by this analysis were subsequently verified in clinical samples and mouse models to further reveal the molecular mechanism of anti-PD-1 resistance in MSI-H or dMMR mCRC. Methods The response of primary and metastatic lesions to first-line anti-PD-1 monotherapy was evaluated by radiology. Cells from primary lesions of patients with MSI-H/dMMR mCRC were analyzed using scRNA-seq. To identify the marker genes in each cluster, distinct cell clusters were identified and subjected to subcluster analysis. Then, a protein‒protein interaction network was constructed to identify key genes. Immunohistochemistry and immunofluorescence were applied to verify key genes and cell marker molecules in clinical samples. Immunohistochemistry, quantitative real-time PCR, and western blotting were performed to examine the expression of IL-1β and MMP9. Moreover, quantitative analysis and sorting of myeloid-derived suppressor cells (MDSCs) and CD8+ T cells were performed using flow cytometry. Results Tumor responses in 23 patients with MSI-H/dMMR mCRC were evaluated by radiology. The objective response rate was 43.48%, and the disease control rate was 69.57%. ScRNA-seq analysis showed that, compared with the treatment-resistant group, the treatment-sensitive group accumulated more CD8+ T cells. Experiments with both clinical samples and mice indicated that infiltration of IL-1β-driven MDSCs and inactivation of CD8+ T cells contribute to anti-PD-1 resistance in MSI-H/dMMR CRC. Conclusions CD8+ T cells and IL-1β were identified as the cell type and gene, respectively, with the highest correlation with anti-PD-1 resistance. Infiltration of IL-1β-driven MDSCs was a significant factor in anti-PD-1 resistance in CRC. IL-1β antagonists are expected to be developed as a new treatment for anti-PD-1 inhibitor resistance.

Abstract Background The identification and enumeration of medicinal plants at high elevations is an important part of accurate yield calculations. However, the current assessment of medicinal plant reserves continues to rely on field sampling surveys, which are cumbersome and time-consuming. Recently, unmanned aerial vehicle (UAV) remote sensing and deep learning (DL) have provided ultrahigh-resolution imagery and high-accuracy object recognition techniques, respectively, providing an excellent opportunity to improve the current manual surveying of plants. However, accurate segmentation of individual plants from drone images remains a significant challenge due to the large variation in size, geometry, and distribution of medicinal plants. Results In this study, we proposed a new pipeline for wild medicinal plant detection and yield assessment based on UAV and DL that was specifically designed for detecting wild medicinal plants in an orthomosaic. We used a drone to collect panoramic images of Lamioplomis rotata Kudo (LR) in high-altitude areas. Then, we annotated and cropped these images into equally sized sub-images and used a DL model Mask R-CNN for object detection and segmentation of LR. Finally, on the basis of the segmentation results, we accurately counted the number and yield of LRs. The results showed that the Mask R-CNN model based on the ResNet-101 backbone network was superior to ResNet-50 in all evaluation indicators. The average identification precision of LR by Mask R-CNN based on the ResNet-101 backbone network was 89.34%, while that of ResNet-50 was 88.32%. The cross-validation results showed that the average accuracy of ResNet-101 was 78.73%, while that of ResNet-50 was 71.25%. According to the orthomosaic, the average number and yield of LR in the two sample sites were 19,376 plants and 57.93 kg and 19,129 plants and 73.5 kg respectively. Conclusions The combination of DL and UAV remote sensing reveals significant promise in medicinal plant detection, counting, and yield prediction, which will benefit the monitoring of their populations for conservation assessment and management, among other applications.

Path planning for quadcopters has been proven to be one kind of NP-hard problem with huge search space and tiny feasible solution range. Metaheuristic algorithms are widely used in such types of problems for their flexibility and effectiveness. Nevertheless, most of them cannot meet the needs in terms of efficiency and suffer from the limitations of premature convergence and local minima. This paper proposes a novel algorithm named Heuristic Hybrid Particle Swarm Optimization (HHPSO) to address the path planning problem. On the heuristic side, we use the control points of cubic b-splines as variables instead of waypoints and establish some heuristic rules during algorithm initialization to generate higher-quality particles. On the hybrid side, we introduce an iteration-varying penalty term to shrink the search range gradually, a Cauchy mutation operator to improve the exploration ability, and an injection operator to prevent population homogenization. Numerical simulations, physical model-based simulations, and a real-world experiment demonstrate the proposed algorithm’s superiority, effectiveness and robustness.

Nephrotic syndrome (NS) is a relatively rare and serious presentation of IgA nephropathy (IgAN) (NS-IgAN). Previous research has suggested that the pathogenesis of NS-IgAN may involve circulating immune imbalance and kidney injury; however, this has yet to be fully elucidated. To investigate the cellular and molecular status of NS-IgAN, we performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) and kidney cells from pediatric patients diagnosed with NS-IgAN by renal biopsy. Consistently, the proportion of intermediate monocytes (IMs) in NS-IgAN patients was higher than in healthy controls. Furthermore, flow cytometry confirmed that IMs were significantly increased in pediatric patients with NS. The characteristic expression of VSIG4 and MHC class II molecules and an increase in oxidative phosphorylation may be important features of IMs in NS-IgAN. Notably, we found that the expression level of CCR2 was significantly increased in the CMs, IMs, and NCMs of patients with NS-IgAN. This may be related to kidney injury. Regulatory T cells (Tregs) are classified into two subsets of cells: Treg1 (CCR7high, TCF7high, and HLA-DRlow) and Treg2 (CCR7low, TCF7low, and HLA-DRhigh). We found that the levels of Treg2 cells expressed significant levels of CCR4 and GATA3, which may be related to the recovery of kidney injury. The state of NS in patients was closely related to podocyte injury. The expression levels of CCL2, PRSS23, and genes related to epithelial-mesenchymal transition were significantly increased in podocytes from NS-IgAN patients. These represent key features of podocyte injury. Our analysis suggests that PTGDS is significantly downregulated following injury and may represent a new marker for podocytes. In this study, we systematically analyzed molecular events in the circulatory system and kidney tissue of pediatric patients with NS-IgAN, which provides new insights for targeted therapy in the future.

Background: Dementia has become one of the leading causes of death across the world. Aims: The aim of this study was to investigate the incidence, prevalence, and mortality of dementia in China between 2010 and 2020, and to investigate any geographical, age, and sex differences in the prevalence and incidence of dementia. Methods: Five databases were searched. The Joanna Briggs Institute (JBI) critical appraisal tool was used to assess the quality of the included studies. A random-effects meta-analysis was performed to estimate the pooled prevalence of dementia. Subgroup analysis was based on the type of dementia. The incidence and mortality of dementia were synthesized qualitatively. Results: A total of 19 studies were included. The meta-analysis showed that the prevalence of dementia was 6% (95%CI 5%, 8%), the prevalence of Alzheimer’s disease (AD) was 5% (95%CI 4%, 6%), and the prevalence of vascular dementia (VaD) was 1% (95%CI 0%, 2%). The subgroup analysis showed that the prevalence rates of dementia in rural (6%, 95%CI 4%, 8%) and urban areas were similar (6%, 95%CI 4%, 8%). Deaths due to dementia increased over time. Conclusion: The prevalence, incidence, and mortality of dementia increased with age and over time. Applying consistent criteria to the diagnosis of cognitive impairment and dementia is necessary to help with disease monitoring. Promoting dementia knowledge and awareness at the community level is necessary.

Abstract This study revisits the question of “whether firms are doing well by doing good?”. We examine shareholders-sponsored corporate socially responsible (CSR) proposals related to Environmental, Social, and Governance (ESG) that are voted to pass or fail by a small margin. The adoption of those “close call” proposals is regarded as equivalent to a random assignment of CSR policies and, therefore, provides a quasi-experimental setting to capture the causal influence of CSR on firm performance. We apply the regression discontinuity design (RDD) and find that CSR proposals’ passage leads to a significant positive abnormal return on the voting day. The results are robust with both parametric and nonparametric approaches of RDD and different polynomial orders. However, we fail to identify a significant change in financial performance in the long-term. One possible reason is that passing a CSR proposal could be symbolic, rather than substantial.

Path planning algorithms are widely used in various motion planning tasks, such as robot motion and autonomous driving.So far, many excellent path planning algorithms have been proposed for applications in different fields.For a specific task environment, choosing the appropriate path planning algorithm can plan a better path that satisfies the constraints more efficiently.Based on the results of swarm intelligence, the adaptability and path planning efficiency of rapidly-exploring random tree (RRT) path planning algorithm and its variants RRT-Star path planning algorithm and RRT-Star-Smart path planning algorithm under different task environments were studied.Using genetic programming algorithm as a framework to design a system, which could automatically analyze the map features of the current environment and combine the characteristics of RRT path planning algorithm and its variants to generate new path planning algorithms that were more suitable for the current environment.The generated path planning algorithm can efficiently plan a feasible path from the starting point to the target point.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide. In China, most HCC patients are diagnosed with advanced disease and in these cases surgery is challenging. Conversion therapy can be used to change unresectable HCC into resectable disease and is a potential breakthrough treatment strategy. The resection rate for unresectable advanced HCC has recently improved as a growing number of patients have benefited from conversion therapy. While conversion therapy is at an early stage of development, progress in patient selection, optimum treatment methods, and the timing of surgery have the potential to deliver significant benefits. In this article, we review the current evidence and clinical experience of conversion therapy in HCC. General conversion modalities such as systemic treatments (systemic chemotherapy, targeted therapy, or immunotherapy), locoregional therapy (transarterial chemoembolization, hepatic arterial infusion chemotherapy, or selective internal radiation therapy), and combination therapy were summarized. We also discuss the current challenges of conversion therapy and provide identify areas for future research to improve the development of conversion therapy in advanced HCC.

Background: Colorectal cancer (CRC) is the third most common cancer and one of the leading causes of death worldwide. Seriously threatens human life and health. Previous studies have identified that inhibin βA (INHBA) could induce tumorgenesis and progression of CRC through the regulation of the TGF-β/Smad signal axis. The abnormal expression of INHBA is related to the poor prognosis of patients. The aim of this study was to identify the molecular mechanism of HNF1A-AS1 and miR-214 regulating INHBA and carcinogenesis through bioinformatics combined with experiments. Methods: The expression of HNF1A-AS1, miRNA-214-5p, INHBA in pan-cancer and CRC were investigated in the Cancer Genome Atlas (TCGA). The correlation between HNF1A-AS1 and immune-related genes or miRNAs was explored via the Gene Expression Profiling Interactive Analysis (GEPIA) and volcano plots, respectively. The association between HNF1A-AS1 and differentially expressed miRNAs was constructed by TargetScan. The miRDB, miRWalk, and TargetScan databases were utilized to predict the target genes of hsa-miR-214. The expression of INHBA in tissues and cell lines of CRC was examined by RT-qPCR and western blot assay. Results: The INHBA and HNF1A-AS1 expressions were increased in Colon adenocarcinoma (COAD) and Rectum adenocarcinoma (READ) of the TCGA database. Hsa-miR-214 was relatively less expressed in CRC tissues compared with para-cancer tissues. The expression of HNF1A-AS1 was negatively correlated with hsa-miR-214. INHBA was one of the target genes of hsa-miR-214 based on miRDB, miRWalk, and TargetScan databases. The specific binding sites of INHBA-3’UTR and miR-214-5p were identified by starBase. The expression level of INHBA was positively correlated with the T stage of tumor and negatively correlated with overall survival (OS) and disease-free survival (DFS) in CRC patients. The results of RT-qPCR and western blot indicated that the expression of INHBA in tissues and cell lines in CRC was higher than those in para-carcinoma tissues and normal colon cell lines, respectively. Conclusions: These findings suggested that HNF1A-AS1 and miRNA-214-5p were key upstream non-coding RNAs of INHBA. The HNF1A-AS1/miR-214/INHBA signal axis plays a significant role in the tumorgenesis and progression of CRC. By interfering with HNF1A-AS1 and INHBA genes on HT29 and SW480 cells, it was found that HNF1A-AS1 and INHBA genes may be important target genes in CRC.

Abstract Background Multiple myeloma (MM) is a complex disease affected by many factors. The recognition of miRNA networks is helpful for specific detection and personalised treatment. Methods mRNA expression profiles were obtained from GSE39754 and GSE87830, and differentially expressed mRNAs (DEmRs) between MM and controls were identified. The intersection of the two sets of DEmRs in GSE39754 and GSE87830 was identified as common mRNAs, and enrichment analysis was subsequently performed. Moreover, we analysed differentially expressed miRNAs (DEmiRs) between MM and controls in GSE87830. A regulatory network of target mRNAs related to the overall survival of MM patients was then constructed. Results In this study, a total of 356 common mRNAs were identified that were significantly enriched in neutrophil-mediated immunity, Th17 cell differentiation and PI3K-Akt signalling pathways. Moreover, we identified 103 DEmiRs and predicted 91 differentially expressed mRNAs as target mRNAs. Cox regression analysis was used to screen 14 target mRNAs that significantly affected the survival of MM patients. In the constructed integrated regulatory network, HIF1A and THBS1 were found to participate in Th17 cell differentiation and PI3K-Akt signalling pathways. Conclusion These findings improve the understanding of the regulatory mechanisms of MM. Genes that are part of integrated regulatory networks may represent candidate targets for MM treatment.

BackgroundThe incidence of kidney, bladder, and prostate cancer ranked ninth, sixth, and third in male cancers respectively, meanwhile, the incidence of testicular cancer also increased gradually in the past 30 years.ObjectiveTo study and present estimates of the incidence, mortality, and disability of kidney, bladder, prostate, and testicular cancer by location and age from 1990 to 2019 and reveal the mortality risk factors of them.MaterialsThe Global Burden of Diseases Study 2019 was used to obtain data for this research. The prediction of cancer mortality and incidence was based on mortality-to-incidence ratios (MIRs). The MIR data was processed by logistic regression and adjusted by Gaussian process regression. The association between the socio-demographic index and the incidence or disease burden was determined by Spearman's rank order correlation.ResultsGlobally in 2019, there were 371,700 kidney cancer cases with an age-standardized incidence rate (ASIR) of 4.6 per 100,000, 524,300 bladder cancer cases, with an ASIR of 6.5 per 100,000, 1,410,500 prostate cancer cases with an ASIR of 4.6 per 100,000 and 109,300 testicular cancer incident cases with an ASIR of 1.4 per 100,000, the ASIR of these four cancers increased by 29.1, 4, 22, and 45.5% respectively. The incidence rate of the four cancers and the burden of kidney cancer were positively correlated with the socio-demographic index (SDI), regions with a higher SDI faced more of a burden attributable to these four cancers. High body-mass index has surpassed smoking to be the leading risk factor in the past thirty years for kidney cancer mortality. Smoking remained the leading risk factor for cancer-related mortality for bladder cancer and prostate cancer and the only risk factor for prostate cancer. However, the contribution of high fasting plasma glucose to bladder cancer mortality has been increasing.ConclusionThe incidence of bladder, kidney, prostate, and testicular cancer is ever-increasing. High-income regions face a greater burden attributable to the four cancers. In addition to smoking, metabolic risk factors may need more attention.

Peripheral blood immune cells have different molecular characteristics at different stages of the whole lifespan. Knowledge of circulating immune cell types and states from children to centenarians remains incomplete. We profiled peripheral blood mononuclear cells (PBMCs) of multiple age groups with single-cell RNA sequencing (scRNA-seq), involving the age ranges of 1-12 (G1), 20-30(G2), 30-60(G3), 60-80(G4), and >110 years (G5). The proportion and states of myeloid cells change significantly from G1 to G2. We identified a novel CD8+CCR7+GZMB+ cytotoxic T cell subtype specific in G1, expressing naive and cytotoxic genes, and validated by flow cytometry. CD8+ T cells showed significant changes in the early stage (G1 to G2), while CD4+ T cells changed in the late stage (G4 to G5). Moreover, the intercellular crosstalk among PBMCs in G1 is very dynamic. Susceptibility genes for a variety of autoimmune diseases (AIDs) have different cell-specific expression localization, and the expression of susceptibility genes for AIDs changes with age. Notably, the CD3+ undefined T cells clearly expressed susceptibility genes for multiple AIDs, especially in G3. ETS1 and FLI1, susceptibility genes associated with systemic lupus erythematosus, were differentially expressed in CD4+ and CD8+ effector cells in G1 and G3. These results provided a valuable basis for future research on the unique immune system of the whole lifespan and AIDs.

To achieve an accurate and comprehensive characterization of the multiscale pore–fracture characteristics of Permian coal in the Jingbian Block, Ordos Basin, a combination of scanning electron microscopy (SEM), X-ray computed tomography (CT), and nuclear magnetic resonance (NMR) techniques was utilized. With these experiments, the mineral composition, pore size distribution (PSD), porosity, and connectivity of pores in coal samples were characterized through qualitative and quantitative methods. The results show that the SEM experiments enabled qualitative identification of pores and mineral types. The coal samples primarily contained gas pores, cell pores, intercrystalline pores, and moldic pores, and clay minerals were the predominant fracture fillings. The 3D reconstruction of the CT experiments shows that the pores and fractures generally expand horizontally, while the minerals show obvious bedding expansion characteristics. Moreover, the estimation of full-size porosity in coal samples can be achieved by combining CT and NMR experiments. The full-size porosity of samples G11-5-1, G11-5-6, G11-5-9, and G11-5-11 was 8.93%, 9.11%, 10.45%, and 11.63%, respectively. The connectivity differences are primarily determined by the throat development degree and the connected pore–fracture count. Samples with more connected pores and larger throat radii exhibit excellent connectivity.

ObjectiveTo explore the efficacy and safety of single-agent programmed cell death protein-1 (PD-1) inhibitor in the neoadjuvant treatment of patients with mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) locally advanced colorectal cancer (LACRC) through single-center large⁃sample analysis based on real⁃world data in China.MethodsThis study was a retrospective, single-center, case series study. 33 colorectal cancer (CRC) patients with clinical stage of T3~4N0~2M0 treated in Yunnan Cancer Hospital from June 2019 to June 2021 were analyzed retrospectively. Among them, 32 patients were dMMR or MSI-H or both dMMR and MSI-H, and one patient was both dMMR and microsatellite stability (MSS) (excluded in the final analysis). All 32 patients received neoadjuvant immunotherapy (nIT) with single-agent PD⁃1 inhibitor.ResultsAmong the 32 patients, 8 (25%) were locally advanced rectal cancer (LARC) and 24 (75%) were locally advanced colon cancer (LACC); 4 (12.55%) were stage II and 28 (87.5%) were stage III. The median number of cycles of 32 patients with dMMR/MSI-H LACRC receiving nIT with single-agent PD-1 blockade was 6 (4~10), and the median number of cycles to achieve partial response (PR) was 3 (2~4). Among them, three LARC patients achieved clinical complete response (cCR) and adopted the watch-and-wait (W&W) strategy. The objective response rate (ORR) of the other 29 patients with radical surgery was 100% (29/29), the pathological response rate was 100% (29/29), the rate of major pathological response (MPR) was 86.2% (25/29), and the rate of pathological complete response (pCR) was 75.9% (22/29). The incidence of immune-related adverse events (irAEs) in 32 patients during nIT was 37.5% (12/32), while the incidence of irAEs in 22 patients with operation during adjuvant immunotherapy was 27.3% (6/22), all of which were grade 1~2. No grade 3 or above irAEs were occured. The median time from the last nIT to surgery was 27 (16~42) days. There were no delayed radical resection due to irAEs in these patients. All 29 patients achieved R0 resection. The incidence of surgical-related adverse events (srAEs) in perioperative period was 10.3% (3/29).ConclusionsNeoadjuvant monoimmunotherapy with PD-1 inhibitor has favorable ORR and pCR rate, and relatively low incidences of irAEs and srAEs for patients with dMMR/MSI-H LACRC, suggesting that this nIT regimen of single-agent PD-1 inhibitor is significantly effective and sufficiently safe.

Abstract Background COVID-19 has resulted in high mortality worldwide. Information regarding cardiac markers for precise risk-stratification is limited. We aim to discover sensitive and reliable early-warning biomarkers for optimizing management and improving the prognosis of COVID-19 patients. Methods A total of 2954 consecutive COVID-19 patients who were receiving treatment from the Wuhan Huoshenshan Hospital in China from February 4 to April 10 were included in this retrospective cohort. Serum levels of cardiac markers were collected after admission. Coronary artery disease diagnosis and survival status were recorded. Single-cell RNA-sequencing and bulk RNA-sequencing from different cohorts of non-COVID-19 were performed to analyze SARS-CoV-2 receptor expression. Results Among 2954 COVID-19 patients in the analysis, the median age was 60 years (50–68 years), 1461 (49.5%) were female, and 1515 (51.3%) were severe/critical. Compared to mild/moderate (1439, 48.7%) patients, severe/critical patients showed significantly higher levels of cardiac markers within the first week after admission. In severe/critical COVID-19 patients, those with abnormal serum levels of BNP (42 [24.6%] vs 7 [1.1%]), hs-TNI (38 [48.1%] vs 6 [1.0%]), α- HBDH (55 [10.4%] vs 2 [0.2%]), CK-MB (45 [36.3%] vs 12 [0.9%]), and LDH (56 [12.5%] vs 1 [0.1%]) had a significantly higher mortality rate compared to patients with normal levels. The same trend was observed in the ICU admission rate. Severe/critical COVID-19 patients with pre-existing coronary artery disease (165/1,155 [10.9%]) had more cases of BNP (52 [46.5%] vs 119 [16.5%]), hs-TNI (24 [26.7%] vs 9.6 [%], α- HBDH (86 [55.5%] vs 443 [34.4%]), CK-MB (27 [17.4%] vs 97 [7.5%]), and LDH (65 [41.9%] vs 382 [29.7%]), when compared with those without coronary artery disease. There was enhanced SARS-CoV-2 receptor expression in coronary artery disease compared with healthy controls. From regression analysis, patients with five elevated cardiac markers were at a higher risk of death (hazards ratio 3.4 [95% CI 2.4–4.8]). Conclusions COVID-19 patients with pre-existing coronary artery disease represented a higher abnormal percentage of cardiac markers, accompanied by high mortality and ICU admission rate. BNP together with hs-TNI, α- HBDH, CK-MB and LDH act as a prognostic biomarker in COVID-19 patients with or without pre-existing coronary artery disease.

The effects of Danggui Sini decoction on peripheral neuropathy in oxaliplatin-induced peripheral is established. The results indicated that Danggui Sini decoction treatment significantly reduced the current amplitude of dorsal root ganglia cells undergoing agonists stimuli compared to the model-dorsal root ganglia group (P Danggui Sini decoction treatment significantly inhibited the inflammatory response of dorsal root ganglia cells compared to the model-dorsal root ganglia group (P Danggui Sini decoction treatment significantly enhanced the amounts of Nissl bodies in dorsal root ganglia cells compared to the Model-dorsal root ganglia group (P Danggui Sini decoction treatment improved ultra-microstructures of dorsal root ganglia cells. In conclusion, Danggui Sini decoction protected against neurotoxicity of oxaliplatin-induced peripheral neuropathy in rats by suppressing inflammatory lesions, improving ultra-microstructures, and enhancing amounts of Nissl bodies.

Patients with locally advanced colorectal cancer (LACRC) have a high risk of recurrence and metastasis, although neoadjuvant therapy may provide some benefit. However, patients with high microsatellite instability/deficient mismatch repair (MSI-H/dMMR) LACRC receive little benefit from neoadjuvant chemoradiotherapy (nCRT) or neoadjuvant chemotherapy (nCT). The 2015 KEYNOTE-016 trial identified MSI-H/dMMR as a biomarker indicative of immunotherapy efficacy, and pointed to the potential use of immune checkpoint inhibitors (ICIs). In 2017, the FDA approved two ICIs (pembrolizumab and nivolumab) for treatment of MSI-H/dMMR metastatic CRC (mCRC). In 2018, the CheckMate-142 trial demonstrated successful treatment of mCRC based on “double immunity” provided by nivolumab with ipilimumab, a regimen that may become a standard first-line treatment for MSI-H mCRC. In 2018, the FDA approved nivolumab alone or with ipilimumab for patients who progressed to MSI-H/dMMR mCRC after standard chemotherapy. The FDA then approved pembrolizumab alone as a first-line treatment for patients with MSI-H/dMMR CRC that was unresectable or metastatic. There is now interest in using these drugs in neoadjuvant immunotherapy (nIT) for patients with MSI-H/dMMR non-mCRC. In 2020, the NICHE trial marked the start of using nIT for CRC. This novel treatment of MSI-H/dMMR LACRC may change the approaches used for neoadjuvant therapy of other cancers. Our review of immunotherapy for CRC covers diagnosis and treatment, clinical prognostic characteristics, the mechanism of nIT, analysis of completed prospective and retrospective studies, and ongoing clinical trials, and the clinical practice of using nIT for MSI-H/dMMR LACRC. Our team also proposes a new organ-preservation strategy for patients with MSI-H/dMMR low LARC.

Introduction: Lenvatinib is the first-line treatment for advanced hepatocellular carcinoma (HCC). We aimed to compare the clinical outcomes of lenvatinib plus drug-eluting beads transarterial chemoembolization (DEB-TACE) versus lenvatinib alone in real-world practice. Methods: This retrospective analysis included 142 consecutive patients who received lenvatinib plus DEB-TACE and 69 patients who received lenvatinib alone as first-line treatment from 15 Chinese academic centers from Nov 2018 to Nov 2019. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) evaluated by mRECIST criteria, and safety profiles were compared between the two groups. Results: The median OS and PFS were significantly longer in the combined therapy group than in the monotherapy group in whole cohort (median OS, 15.9 vs 8.6 months, p=0.0022; median PFS, 8.6 vs 4.4 months, p

Abstract Background Shilajit is a commonly used Tibetan medicine, and its water extract is mainly used for various heat-related syndrome, especially that of stomach, liver and kidney. Shilajit is found to exudate from rocks of cliff at an altitude of 2000–4000 m as a water-soluble mixture of black paste and animal feces of Trodocterus spp. or Ochotona spp. Because it is difficult to reach the exudation points so as to explain the its formation process, the source of Shilajit still remains unclear and controversial, which severely impedes its safety and efficacy in clinical application. Methods In this work, a series of investigations as rock flakes identification, porosity determination, rock mineral analysis, scanning electron microscopy (SEM), and energy dispersive spectrometer (EDS) have been carried out to clarify the source of Shilajit, including the storage condition and exudation process of its organic matter, and to investigate the geological structure of the exudation points as well as physical and chemical characteristics of the mother rocks. Results The Shilajit exudation points were mainly distributed on the steep cliffs, where there were cavities and sections that could not be eroded by rainwater. The fundamental structure of the exudation points was determined by the rock’s bedding planes, joints, fracture surfaces and faults, and developed into micro-topography later. The exudation points were distributed in the Triassic strata and scattered in the Early Mesozoic granitoids. The lithologic features were mainly slate, carbonaceous slate and sandy slate etc. The background rocks were characterized by intergranular pores, dissolved pore, joint and fracture development. Organic matter was widely distributed in these pores and fissures, which had condition for storage and exudation of organic matter. Conclusions Shilajit mainly distributed on sunny steep slopes and cliffs with a slope of 60° or above at altitude of 2000–4000 m. The lithology character of the Shilajit exudation area were mainly various metamorphic rocks of sedimentary rocks that were rich in organic carbon. The organic matter in Shilajit was found to flow out naturally from rocks along pore, structural plane and even accumulate on the surface of rock as a result of storage environment change caused by rock tectonic action.

Erlian Basin is a Mesozoic oil and gas-bearing basin in northeast of China. The extension rate, extension direction, and stratum thickness of this rift basin have a clear control on its shape and extension. In this study, we design three sandbox models of the Erlian Basin to represent the effects of changing these three factors. The extension rate controls the timing of secondary fault formation inside the rift basin; a high extension rate promotes faster deformation inside the rift. The extension direction controls the strike of the fault inside the rift; a greater angle between the extension direction and the normal direction of the strike of the rift favors rapid evolution of internal secondary faults. The stratum thickness represents the control of sedimentation on the rift basin; the thinner the brittle layer, the wider the rift. The simulation results also show that the extension direction is the major factor controlling tectonic deformation in the basin. Stratum thickness and extension rate are secondary controlling factors. Additionally, according to geometric and kinematic similarities between typical Mesozoic rift basins in eastern and adjacent areas of China, we suggest that southeastward extension is a possible kinematic mechanism for basin formation.

Dynamic detection, as one of the core tenets in tumor diagnosis, relies on specific recognition, rapid reaction, and significant signal output. Circulating tumor cells that carry the most complete information of neoplastic lesions are analytes of interest for sensor designer. To overcome the deficiencies in the use of antibodies, some antibody-like structures were used to integrate chemosensors, such as molecularly imprinted polymers (MIPs) and aptamer conjugates that may perform specific detection of analytes. The sensors inherited from such structurally stable molecular recognition materials have the advantage of being cost-effective, rapid-to-fabricate and easy-to-use, whilst exhibiting specificity comparable to antibody-based kits. Moreover, the fabricated sensors may automatically perform quantitative analysis via digital and microfluidic devices, facilitating advances in wearable sensors, meanwhile bringing new opportunities and challenges. Although most MIPs-based sensors for tumor diagnosis to date have not been practically used in hospitals, with no doubt, material innovation and artificial intelligence development are the driving forces to push the process forward. At the same time, the challenges and opportunities of these sensors moving forward to intelligent and implantable devices are discussed.

Radiofrequency ablation (RFA) is one of the safe and effective treatments of colorectal cancer with liver metastasis, which has the advantages of minimally invasive, fewer complications, short hospitalization time and repeatable operation. A special case with advanced transverse colon carcinoma was treated by RFA in our center. All the procedures were performed, which were recommended by the guideline. An intestinal perforation occurred on the second day after the RFA, then surgeon performed emergency surgery, unfortunately, anastomotic leakage occurred on the 21st day after the operation, yet after conservative medical treatment, the patient achieved remission of symptoms and discharged from the hospital. Rare complications occurred after RFA in the treatment of colorectal cancer with liver metastasis are unpredictable, which could affect the efficacy of RFA and performance status of patients. Further investigation of the mechanism of these complications is warranted urgently, which might offer more effective methods against these rare complications.

The identification of asymptomatic, non-severe presymptomatic, and severe presymptomatic coronavirus disease 2019 (COVID-19) in patients may help optimize risk-stratified clinical management and improve prognosis. This single-center case series from Wuhan Huoshenshan Hospital, China, included 2,980 patients with COVID-19 who were hospitalized between February 4, 2020 and April 10, 2020. Patients were diagnosed as asymptomatic (n = 39), presymptomatic (n = 34), and symptomatic (n = 2,907) upon admission. This study provided an overview of asymptomatic, presymptomatic, and symptomatic COVID-19 patients, including detection, demographics, clinical characteristics, and outcomes. Upon admission, there was no significant difference in clinical symptoms and CT image between asymptomatic and presymptomatic patients for diagnosis reference. The mean area under the receiver operating characteristic curve (AUC) of the differential diagnosis model to discriminate presymptomatic patients from asymptomatic patients was 0.89 (95% CI, 0.81-0.98). Importantly, the severe and non-severe presymptomatic patients can be further stratified (AUC = 0.82). In conclusion, the two-step risk-stratification model based on 10 laboratory indicators can distinguish among asymptomatic, severe presymptomatic, and non-severe presymptomatic COVID-19 patients on admission. Moreover, single-cell data analyses revealed that the CD8+T cell exhaustion correlated to the progression of COVID-19.

Abstract Background This research provides the first evidence of CDK5 in ccRCC prognosis and correlation with different p21 expression in overall survival (OS) analysis. Methods The data from both of The Cancer Genome Atlas (TCGA) and Gene Expression of Normal and Tumor Tissue (GENT) were analyzed for determining the expression of CDK5 in kidney cancer. Tissue microarray that made by using 150 ccRCC samples was used in immunohistochemistry (IHC) analysis. A validation of OS cohort was extracted from Oncomine database. Results The CDK5 expression was significantly lower in cancer tissue compared with normal in TCGA (p

Abstract. Background:. A correct thyroid function reference range is important for the accurate diagnosis of thyroid disease during pregnancy. However, there is no consensus on whether thyroid function reference ranges in Chinese population should follow the America Thyroid Association (ATA) guidelines. This study aimed to establish a thyroid function reference range more suited to the Chinese population by evaluating the current thyroid function reference range in pregnant Chinese women and comparing it to the ATA guidelines. Methods:. A total of 52,027 pregnant women were enrolled from January 2013 to December 2016. Thyroid stimulating hormone (TSH), free thyroxine (FT4), and thyroid peroxidase antibody (TPOAb) levels were tested during the first and third trimesters of pregnancy. Reference ranges of TSH and FT4 were established from the 2.5th and 97.5th percentiles of the TPOAb-negative population of women. The Mann-Whitney U test was used to compare thyroid hormones between the TPOAb-positive and TPOAb-negative groups. Results:. We obtained that the TSH reference ranges were 0.03 to 3.52 mU/L and 0.39 to 3.67 mU/L, and the FT4 reference ranges were 11.7 to 19.7 pmol/L and 9.1 to 14.4 pmol/L, in the first and third trimester, respectively. If we used the 2011 ATA criteria about 7.0% and 4.0% pregnant women would be over diagnosed in first and third trimester, respectively, compared with local population thyroid hormone reference. When we compared our local criteria with the new 2017 ATA criteria, about 1.2% and 0.8% pregnant women would have a missed diagnosis in first and third trimester, respectively. Conclusions:. Based on our data, which is in line with the current ATA guidelines, a population-based thyroid function reference range would be the first choice for diagnosis of thyroid disease during pregnancy in China. In case such population-based thyroid function reference ranges are unavailable in the east of China, our reference ranges can be adopted, if the same assay is used. Trial Registration:. www.chictr.org.cn (No. ChiCTR1800014394).

BackgroundCoronavirus disease 2019 (COVID-19) has rapidly spread worldwide. Systematic analysis of lung cancer survivors at molecular and clinical levels is warranted to understand the disease course and clinical characteristics.MethodsA single-center, retrospective cohort study was conducted in 65 patients with COVID-19 from Wuhan Huoshenshan Hospital, of which 13 patients were diagnosed with lung cancer. The study was conducted from February 4 to April 11, 2020.ResultsDuring the course of treatment, lung cancer survivors infected with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) had shorter median time from symptom onset to hospitalization (P = 0.016) and longer clinical symptom remission time (P = 0.020) than non-cancer individuals. No differences were observed among indicators such as time from symptom onset to hospitalization and symptom remission time between medium-term and short-term survivors. The expression of ACE2 (P = 0.013) and TMPRSS2 (P

Ursodeoxycholic acid (UDCA) is a first-line clinical drug for the treatment of liver diseases. U12, a derivative of UDCA, showed effective anti-hepatoma activities in previous works. However, the low polarity and large doses limited the druglikeness of U12. In this study, the structural modification and optimization of U12 were further investigated and twelve U12 derivatives were synthesized by substitution, esterification and amidation reactions. The evaluation of the cytotoxicity of synthetic derivatives against hepatoma cell lines (HepG2) indicated that U12-I, U12a-d and U12h showed more effective cytotoxic effects on the growth of HepG2 cells than U12, and the preliminary structure–activity relationship was discussed. Among them, U12a exhibited the most potent anti-hepatocellular carcinoma activity. Mechanism studies indicated that U12a inhibited HepG2 cell proliferation by arresting the G0/G1 phase, and suppressed the activation of the PI3K/AKT/mTOR pathway. Further studies showed that U12a induced HepG2 cells apoptosis through activating the caspase signaling pathway. Furthermore, U12a evidently inhibits the growth of HepG2-derived tumor xenografts in vivo without observable adverse effects. Thus, U12a might be considered as a promising candidate for the treatment of hepatocellular carcinoma.

Background/Aims: The placenta has been suggested to play a crucial role in the pathology of gestational diabetes mellitus (GDM). Placenta-specific microRNAs (miRNAs) and the corresponding targeting genes involved in the pathology of GDM still remain to be elucidated. We aimed to identify the dysregulated miRNAs and the corresponding mRNA targets through an integrated miRNA and mRNA transcriptomic profiles analysis and investigate the role of differentially expressed miR-138-5p/TBL1X in GDM. Methods: RNA sequencing (RNA-seq) was performed in 16 placentas from GDM and control group. Differentially expressed mRNAs and miRNAs in GDM were validated by quantitative PCR (qPCR). The wound healing assay and transwell migration assay were used to analyze cell migration ability. The cell proliferation was determined by CCK8 assay. Luciferase assay was used to confirm the direct binding of the targeted TBL1X with miR-138-5p. Results: Totally, 281 mRNAs and 32 miRNAs were found to be differentially expressed in the GDM placentas. The biological relationships of the miRNA/mRNA pairs were related to cellular development and function and organ morphology. Among the aberrantly expressed molecules, we selected miR-138-5p from the bioinformatics analysis and found that miR-138-5p significantly inhibited the migration and proliferation of trophoblasts (HTR-8/SVneo) by targeting the 3’-UTR of TBL1X. Furthermore, the aberrant expression of miR-138-5p and TBL1X was significantly correlated with the weight of the placenta. Conclusion: We present the first integrative analysis of miRNA and mRNA expression profiles in GDM placenta and uncover a more detailed role for miR-138-5p, as well as its target TBL1X in the pathology of GDM.

As the key equipment in deep ocean mining, the slurry pump suffers from wear and blocking problems. In this paper, high-speed photography technique is applied to track the movement rule of single particle of the coarse particle solid–liquid two-phase flow in a double blade slurry pump. The influences of particle diameter and particle density on the pass-through and collision characteristics of particles are analyzed as well. The results show that the average of the passing pump time first decreases and then increases when the particle diameter increases. The average of the passing pump time decreases by 22.7%, when the particle density increases from 1.09 g/cm3 to 1.75 g/cm3. Besides, the particle density has great influence on the location where the particle hits the tongue. Most particles of 1.09 g/cm3 hit the tongue on the left side, while collision location of particles of 1.75 g/cm3 is mainly on the top and at the right side of the tongue. The research can provide a basis for the optimization design of slurry pump in deep ocean mining system.

A Correction to this paper has been published: https://doi.org/10.1038/s41419-021-03678-9

Carcinoembryonic antigen (CEA) is an important broad-spectrum tumor marker. For CEA detection, a novel type of metal–organic framework (MOF) was prepared by grafting CEA aptamer-incorporated DNA tetrahedral (TDN) nanostructures into PCN-222 (Fe)-based MOF (referred as CEAapt-TDN-MOF colloid nanorods). The synthesized CEAapt-TDN-MOF is a very stable detection system due to the vertex phosphorylated TDN structure at the interface, possessing a one-year shelf-life. Moreover, it exhibits a significant horseradish peroxidase mimicking activity due to the iron porphyrin ring, which leads to a colorimetric reaction upon binding toward antibody-captured CEA. Using this method, we successfully achieved the highly specific and ultra-sensitive detection of CEA with a limit of detection as low as 3.3 pg/mL. In addition, this method can detect and analyze the target proteins in clinical serum samples, effectively identify the difference between normal individuals and patients with colon cancer, and provide a new method for the clinical diagnosis of tumors, demonstrating a great application potential.

A novel sorbent based on the ZrO2 nanoparticles and poly(diallyldimethylammonium chloride)-modified graphene oxide aerogel-grafted stainless steel mesh (ZrO2/PDDA-GOA-SSM) was used for the extraction and detection of organophosphorus pesticides (OPPs). Firstly, the PDDA and GO composite was grafted onto the surface of SSM and then freeze-dried to obtain the aerogel, which efficiently reduced the accumulation of graphene nanosheets. It integrated the advanced properties of GOA with a thin coating and the three-dimensional structural geometry of SSM. The modification of ZrO2 nanoparticles brought a selective adsorption for OPPs due to the combination of the phosphate group as a Lewis base and ZrO2 nanoparticles with the Lewis acid site. The ZrO2/PDDA-GOA-SSM was packed into the solid-phase extraction (SPE) cartridge to extract OPPs. According to the investigation of different factors, the extraction recovery was mainly affected by the hydrophilic-hydrophobic properties of analytes. Effective extraction and elution parameters such as sample volume, sample pH, rate of sample loading, eluent, and eluent volume, were also investigated and discussed. Under the optimal conditions, the linearity of phoxim and fenitrothion was in the range of 1.0–200 μg L−1, and the linearity of temephos was in the range of 2.5–200 μg L−1. The limits of detection were ranged from 0.2 to 1.0 μg L−1. This established method was successfully applied to detect OPPs in two vegetables. There was no OPP detected in real samples, and results showed that the matrix effects were in the range of 46.5%–90.1%. This indicates that the ZrO2/PDDA-GOA-SSM-SPE-HPLC method could effectively extract and detect OPPs in vegetables.

In this work, two typical fluorescent sensors were generated by exploiting molecularly imprinted polymeric hydrogels (MIPGs) for zearalenone (ZON) and glucuronic acid (GA) detection, via the analyte’s self-fluorescence property and receptor’s fluorescence effect, respectively. Though significant advances have been achieved on MIPG-fluorescent sensors endowed with superior stability over natural receptor-sensors, there is an increasing demand for developing sensing devices with cost-effective, easy-to-use, portable advantages in terms of commercialization. Zooming in on the commercial potential of MIPG-fluorescent sensors, the MIPG_ZON is synthesized using zearalanone (an analogue of ZON) as template, which exhibits good detection performance even in corn samples with a limit of detection of 1.6 μM. In parallel, fluorescein-incorporated MIPG_GA is obtained and directly used for cancer cell imaging, with significant specificity and selectivity. Last but not least, our consolidated application results unfold new opportunities for MIPG-fluorescent sensors for environmentally and medicinally important analytes detection.

We analyzed the tectonic evolution characteristics, sedimentary environment, geochemical characteristics, petrological characteristics, and gas-bearing properties of three mudstone sections of the Lower Paleozoic in Ningwu Basin, NE China, and determined the geologic characteristics and resource potential of the transitional facies shale gas. Geochemical analysis of the organic carbon content, kerogen macerals, and vitrinite reflectance of the shale samples showed that the total organic content was generally over 2.0%, the main organic type was type III, and the vitrinite reflectance values (Ro) were between 1.20 and 1.90%. Thus, the mudstones are good shale gas source rocks. The thickness of the three mudstone sections was approximately 30–70 m, and the average porosity was 3.10%. The pore types were diverse with good reservoir capacity. The shale gas resources of the Carboniferous-Permian transitional facies estimated by the volumetric method were approximately 2798.97 × 10 8 –4643.09 × 10 8 m 3 . Through a comparison with shales in SW China, where shale gas has been successfully exploited, we determined the preferred criteria for favorable shale gas areas, as well as favorable areas for shale gas enrichment.

Wilms’ tumor is associated with a high treatment success rate, but there is still a risk of recurrence. Cisplatin, which is one of the chemotherapeutic agents used for its treatment, is associated with a very high rate of resistance. Par-4 (prostate apoptosis response 4) is a tumor suppressor, which is capable of sensitizing tumor cells to chemotherapy. Therefore, the aim of this study was to determine whether combined treatment with Par-4 and cisplatin is effective for inhibiting growth of Wilms’ tumor. Wilms’ tumor and control cell samples were collected and analyzed by immunofluorescence assay and immunohistochemistry. Total proteins extracted from cultured cells were analyzed using western blotting and flow cytometry. In addition, a mouse xenograft model was established. We discovered significantly low expression of Par-4 in the tumor tissue, which was positively correlated with high expression of GRP78 (glucose-regulated protein 78). In addition, we found that ectopic Par-4 co-localized with cell surface GRP78 and induced high expression of the endoplasmic reticulum proteins ATF4 and BAX, which activated the endoplasmic reticulum apoptosis pathway. Moreover, treatment with ectopic Par-4 and cisplatin suppressed xenograft growth in nude mice. In conclusion, our results showed that Par-4 overexpression and cisplatin had a synergistic effect on SK-NEP-1 cells, as a result of which cell growth was inhibited and cellular apoptosis was induced. Thus, in vitro and in vivo upregulation of Par-4 expression is indispensable for the trafficking of GRP78 to the cell membrane and subsequent apoptosis of cancer cells.

Many studies have indicated that the expression of interleukin-21 (IL-21) is associated with the pathogenesis of certain liver diseases. However, in alternative animal models of liver diseases, it remains unknown whether the tree shrew could be utilized to analyze the relationship between IL-21 and liver diseases. Here, the phylogenetic tree, sequence alignment and protein structure model of tree shrew and human IL-21 were analyzed using bioinformatics software. A pEGFP-N3/tsIL-21 eukaryotic expression vector of tree shrew IL-21 (tsIL-21) was constructed, and IL-21 expression by the vector-transfected Huh7 cells was evaluated using the newly established quantitative real-time PCR and immunologic protocols for assessing human IL-21. The cytokine profiles were also evaluated in tree shrew spleen lymphocytes induced by recombinant human IL-21 or concanavalin A. It was found that the coding sequence (CDS) of tsIL-21 amplified from spleen lymphocytes belonged to the predicted sequence. The tsIL-21 was closely clustered with primate IL-21 rather than rodent IL-21, and it had an alignment of 83.33% with the human IL-21 nucleotide sequence and 69.93% with the amino acid sequence. The profiles of secondary structure, hydrophobicity and surface charge of tsIL-21 were also similar with those of human IL-21. The tsIL-21 expressed by the vector-transfected Huh7 cells could be identified by their different sources of antibodies against human IL-21, which were all dose-dependent. Recombinant human IL-21 could induce the change of the cytokine profiles of tree shrew spleen lymphocytes, which showed a higher expression of IL-10 and IFN-γ rather than IL-2, IL-4, IL-17, TNF-a and IL-21 during the five-day stimulation. These results indicate that tsIL-21 has a high degree of homology, structural similarity and immunological cross-reactivity with human IL-21 and also confirm the accuracy of this predicted tsIL-21CDS. The protocols utilized in this study will lead to the experimental feasibility of further IL-21-related studies in vivo.