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Abstract Atrial fibrillation is the most common arrhythmia in adults. The interplay between epicardial adipose tissue and atrial fibrillation has garnered significant scientific interest. Recently, the combined approach of radiofrequency ablation and left atrial appendage occlusion has become a widely adopted strategy for managing non-valvular atrial fibrillation patients at high risk of thrombus formation. This study aims to assess the prognostic significance of epicardial adipose tissue volume in patients undergoing radiofrequency ablation in conjunction with left atrial appendage occlusion. This study results indicate that in patients undergoing the one-stop procedure, which comprises catheter radiofrequency ablation and percutaneous left atrial appendage occlusion, epicardial adipose tissue volume is significantly associated with AF recurrence post-strategy. Higher EATV predicts AF recurrence (HR = 1.17, 95%CI1.047-1.192, P = 0.001) and thromboembolism (P = 0.002) following the one-stop procedure. Epicardial adipose tissue volume serves as a significant predictor of atrial fibrillation recurrence following the one-stop procedure (area under the curve 0.648, 95%CI0.571-0.725, P = 0.002, sensitivity 0.88, specificity 0.50).

With water resource shortages becoming a global concern, water conservation is one of the key factors in the sustainable development of watershed ecosystems. However, previous studies of water conservation have focused on annual mean water conservation, which does not reflect changes in water conservation on shorter time scales. Shorter time scales have more significant responses than longer timescales. An annual scale reflects the supply function of the water culverts, whereas a shorter time scale reflects the function of stagnant flood replenishment. Thus, we analyzed the annual, monthly, and daily changes in water conservation in the Zengjiang River Basin, an important water source area and ecological barrier in Guangzhou, from 1959 to 2018. The WEP-L distributed hydrological model and water-balance equations were used to explore the supply, regulation, and peak reduction and replenishment of the water conservation dryness functions. The results indicate that the annual mean water conservation in the Zengjiang River Basin was 685.7 mm from 1959 to 2018, with a non-significant decreasing rate (-1.30 mm/a) during this period. This decreasing trend indicates that the water supply capacity of the basin decreased, which is not conducive to the water security of the basin and downstream areas. Therefore, relevant policies should be formulated and measures should be taken to improve the water conservation capacity of the basin. The multi-year average monthly water conservation in the Zengjiang River Basin was positive in January‒September and negative in October‒December, with non-significant increases in water conservation in January, March, June, November, and December, and non-significant decreases in the other months. The trend ranged from -0.04 to -0.67 mm/a during the entire study period. Water conservation changes in the Zengjiang River Basin during pre-flood, post-flood, and dry-water periods indicate that the basin's ability to regulate water conservation runoff weakened. The maximum 1-day, 3-day, 5-day, and 7-day periods in the Zengjiang River Basin were positive, whereas the minimum 1-day, 3-day, 5-day, and 7-day periods were negative. Except for the minimum 5-day and 7-day periods, the other six daily extreme water conservation indicators exhibited non-significant increasing trends. The maximum water conservation values indicate that the peak reduction capacity increased, while the minimum water conservation values indicate that the capacity to replenish depletion decreased in 1- and 3-day periods and increased in 5- and 7-day periods. Spatially, the annual water conservation trend was low in the southeastern and northern parts of the basin, and high in the southwestern part of the basin. Annual, monthly, and daily water conservation levels in the Zengjiang River Basin from 1959 to 2018 embodied its supply, regulation, peak reduction, and replenishment of depletion functions, respectively. The correlation coefficients between water conservation and precipitation were significantly higher than those between evapotranspiration and surface runoff, thereby indicating that precipitation was the most important factor influencing water conservation. The findings of this study reveal multi-temporal evolutionary processes and functional differences in water conservation and provide a scientific basis for ecological protection and construction.

Abstract Background Emerging evidence indicates the pivotal involvement of circular RNAs (circRNAs) in cancer initiation and progression. Understanding the functions and underlying mechanisms of circRNAs in tumor development holds promise for uncovering novel diagnostic indicators and therapeutic targets. In this study, our focus was to elucidate the function and regulatory mechanism of hsa-circ-0003764 in hepatocellular carcinoma (HCC). Methods A newly discovered hsa-circ-0003764 (circPTPN12) was identified from the circbase database. QRT-PCR analysis was utilized to assess the expression levels of hsa-circ-0003764 in both HCC tissues and cells. We conducted in vitro and in vivo experiments to examine the impact of circPTPN12 on the proliferation and apoptosis of HCC cells. Additionally, RNA-sequencing, RNA immunoprecipitation, biotin-coupled probe pull-down assays, and FISH were employed to confirm and establish the relationship between hsa-circ-0003764, PDLIM2, OTUD6B, P65, and ESRP1. Results In HCC, the downregulation of circPTPN12 was associated with an unfavorable prognosis. CircPTPN12 exhibited suppressive effects on the proliferation of HCC cells both in vitro and in vivo. Mechanistically, RNA sequencing assays unveiled the NF-κB signaling pathway as a targeted pathway of circPTPN12. Functionally, circPTPN12 was found to interact with the PDZ domain of PDLIM2, facilitating the ubiquitination of P65. Furthermore, circPTPN12 bolstered the assembly of the PDLIM2/OTUD6B complex by promoting the deubiquitination of PDLIM2. ESRP1 was identified to bind to pre-PTPN12, thereby fostering the generation of circPTPN12. Conclusions Collectively, our findings indicate the involvement of circPTPN12 in modulating PDLIM2 function, influencing HCC progression. The identified ESRP1/circPTPN12/PDLIM2/NF-κB axis shows promise as a novel therapeutic target in the context of HCC. Graphical Abstract

BackgroundSarcopenia is a significant predictor of perioperative adverse outcomes for a variety of malignancies and has significant negative effects on surgical and oncology outcomes. The development of sarcopenia is mainly attributed to aging, inactivity, poor nutrition, and decreased testosterone levels, which suggest a poor prognosis after surgery. Therefore, the primary objective of this systematic review and meta-analysis was to determine the effect of sarcopenia on postoperative survival in patients with oral squamous cell carcinoma.MethodsWe systematically searched databases including PubMed, Embase, Cochrane Library, Medline and Web of Science from inception to 12 July 2023, to determine the prognostic value of sarcopenia in oral squamous cell carcinoma. The primary outcome was three-year survival, and secondary outcomes were one-year survival, five-year survival, infection and pneumonia within 30 days postoperatively. Original studies comparing postoperative outcomes in patients with sarcopenia and non-sarcopenia for oral squamous cell carcinoma curative therapy were met the eligibility criteria. We used Endnote X9 for the screening process and used RevMan 5.4.1 for our meta-analysis, all results in this study were performed using a random-effects model. QUIPS (Quality in Prognosis Studies) tools and GRADE (Grading of Recommendations, Assessment, Development and Evaluations) were used for risk of bias and quality of evidence assessment.ResultTen original studies with 50611 patients met the inclusion criteria. Meta-analysis showed that patients with sarcopenia reduced three-year OS after surgery (OR = 0.73, 95% CI = 0.66-0.81, P < 0.00001). The one-year OS (OR = 0.71, 95% CI = 0.67-0.75, P < 0.00001) and five-year OS (OR = 0.60, 95% CI = 0.45-0.79, P = 0.0003) decreased significantly. Patients with sarcopenia had significantly increased 30-day postoperative mortality and an also increased risk of pneumonia (OR = 1.36, 95% CI = 1.24-1.49, P < 0.00001) and surgical site infection (OR = 2.49, 95% CI = 1.06-5.84, P = 0.04).ConclusionSarcopenia is associated with reduced survival in patients after curative resection. Meanwhile, 30-day mortality, postoperative pneumonia and surgical site infection were significantly higher than those in nonsarcopenic patients. Sarcopenia as an extremely important factor of postoperative adverse outcomes in OSCC patients need special attention.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023444424.

Abstract Background Endotracheal intubation is often associated with postoperative complications such as sore throat discomfort and hoarseness, reducing patient satisfaction and prolonging hospital stays. Laryngeal mask airway (LMA) plays a critical role in reducing airway complications related to endotracheal intubation. This meta-analysis was performed to determine the efficacy and safety of LMA in video-assisted thoracic surgery (VATS). Methods The PubMed, Embase, Cochrane Library, Medline and Web of Science databases were searched for eligible studies from inception until October 5, 2023. Cochrane’s tool (RoB 2) was used to evaluate the possibility biases of RCTs. We performed sensitivity analysis and subgroup analysis to assess the robustness of the results. Results Seven articles were included in this meta-analysis. Compared with endotracheal intubation, there was no significant difference in the postoperative hospital stay (SMD = -0.47, 95% CI = -0.98–0.03, P = 0.06), intraoperative minimum SpO2 (SMD = 0.00, 95% CI = -0.49–0.49, P = 1.00), hypoxemia (RR = 1.00, 95% CI = 0.26–3.89, P = 1.00), intraoperative highest PetCO2 (SMD = 0.51, 95% CI = -0.12–1.15, P = 0.11), surgical field satisfaction (RR = 1.01, 95% CI = 0.98–1.03, P = 0.61), anesthesia time (SMD = -0.10, 95% CI = -0.30–0.10, P = 0.31), operation time (SMD = 0.06, 95% CI = -0.13–0.24, P = 0.55) and blood loss (SMD =- 0.13, 95% CI = -0.33–0.07, P = 0.21) in LMA group. However, LMA was associated with a lower incidence of throat discomfort (RR = 0.28, 95% CI = 0.17–0.48, P

Abstract Introduction Postoperative nausea and vomiting (PONV) is one of the most common adverse events following orthognathic surgery. It’s a distressing feeling for patients and continues to be the cause of postoperative complications such as bleeding, delayed healing, and wound infection. This scoping review aims to identify effective PONV prophylaxis strategies during orthognathic surgery that have emerged in the past 15 years. Methods We searched Pubmed, Cochrane Controlled Register of Trials, and Embase from 2008 to May 2023. Studies meeting the following criteria were eligible for inclusion: (1) recruited patients undergo any orthognathic surgery; (2) evaluated any pharmacologic or non-pharmacologic method to prevent PONV. Studies meeting the following criteria were excluded: (1) case series, review papers, or retrospective studies; (2) did not report our prespecified outcomes. Results Twenty-one studies were included in this review. Pharmacological methods for PONV prevention include ondansetron and dexamethasone (3 studies), peripheral nerve block technique (4 studies), dexmedetomidine (1 study), pregabalin (2 studies), nefopam (2 studies), remifentanil (1 study), propofol (2 studies), and penehyclidine (1 study). Non-pharmacologic methods include capsicum plaster (1 study), throat packs (2 studies) and gastric aspiration (2 studies). Conclusions Based on current evidence, we conclude that prophylactic antiemetics like dexamethasone, ondansetron, and penehyclidine are the first defense against PONV. Multimodal analgesia with nerve block techniques and non-opioid analgesics should be considered due to their notable opioid-sparing and PONV preventive effect. For the non-pharmacological methods, throat packs are not recommended for routine use because of their poor effect and serious complications. More prospective RCTs are required to confirm whether gastric aspiration can prevent PONV effectively for patients undergoing orthognathic surgery.

Abstract Background and objectives Colorectal mucinous adenocarcinoma (MAC) is a particular pathological type that has yet to be thoroughly studied. This study aims to investigate the characteristics of colorectal MAC-related genes in colorectal cancer (CRC), explore the role of MAC-related genes in accurately classifying CRC, and further construct a prognostic signature. Methods CRC samples were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). MAC-related differentially expressed genes (DEGs) were analyzed in TCGA samples. Based on colorectal MAC-related genes, TCGA CRC samples were molecularly typed by the non-negative matrix factorization (NMF). According to the molecular subtype characteristics, the RiskScore signature was constructed through univariate Cox, the least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses. Clinical significance in CRC of the RiskScore signature was analyzed. A nomogram was further built based on the RiskScore signature. Results From the colorectal MAC-related genes, three distinct molecular subtypes were identified. A RiskScore signature composed of six CRC subtype-related genes (CALB1, MMP1, HOXC6, ZIC2, SFTA2, and HYAL1) was constructed. Patients with high-RiskScores had the worse prognoses. RiskScores led to differences in gene mutation characteristics, antitumor drug sensitivity, and tumor microenvironment of CRC. A nomogram based on the signature was developed to predict the one-, three-, and five-year survival of CRC patients. Conclusion MAC-related genes were able to classify CRC. A RiskScore signature based on the colorectal MAC-related molecular subtype was constructed, which had important clinical significance for guiding the accurate stratification of CRC patients.

Background Cardiovascular disease is a major chronic disease that seriously endangers human health, and remains a public health problem to be solved in China and even globally. Objective To explore the epidemic characteristics and disease burden of cardiovascular diseases in China from 1990 to 2019, forecast the incidence of cardiovascular diseases in China from 2020 to 2050, and provide a reference for the formulation of relevant prevention and treatment strategies of cardiovascular diseases. Methods The 2019 Global Burden of Disease Study (GBD 2019) database was searched to extract and analyze relevant data on cardiovascular disease burden and risk factors in China and globally from 1990 to 2019. The prevalence of cardiovascular diseases was quantified by using the publicly available incidence, prevalence, mortality, and corresponding age-standardized rate (referred to as standardized rate) based on GBD 2019 database, and the burden of diseases was quantified by years lived with disability (YLD), years of life lost (YLL) and disability adjusted life year (DALY), and the ARIMA model was constructed to predict the incidence of cardiovascular diseases in China from 2020 to 2050. Results Compared with 1990, the incidence, prevalence and mortality of cardiovascular diseases in China showed an increasing trend by year up to 2019, in which the incidence, prevalence and mortality increased by 93.75%, 99.75% and 57.39%, respectively. The standardized incidence and prevalence of females were higher than those of males, while the standardized mortality was lower than that of males (P

The emotional expression of body movement, which is an aspect of emotional communication between humans, has not been considered enough in the field of human–robot interactions (HRIs). This paper explores human perceptions of the emotional expressions of humanoid robot body movements to study the emotional design of the bodily expressions of robots and the characteristics of the human perception of these emotional body movements. Six categories of emotional behaviors, including happiness, anger, sadness, surprise, fear, and disgust, were designed by imitating human emotional body movements, and they were implemented on a Yanshee robot. A total of 135 participants were recruited for questionnaires and eye-tracking measurements. Statistical methods, including K-means clustering, repeated analysis of variance (ANOVA), Friedman’s ANOVA, and Spearman’s correlation test, were used to analyze the data. According to the statistical results of emotional categories, intensities, and arousals perceived by humans, a guide to grading the designed robot’s bodily expressions of emotion is created. By combining this guide with certain objective analyses, such as fixation and trajectory of eye movements, the characteristics of human perception, including the perceived differences between happiness and negative emotions and the trends of eye movements for different emotional categories, are described. This study not only illustrates subjective and objective evidence that humans can perceive robot bodily expressions of emotions through only vision but also provides helpful guidance for designing appropriate emotional bodily expressions in HRIs.

Student dropout prediction (SDP) in educational research has gained prominence for its role in analyzing student learning behaviors through time series models. Traditional methods often focus singularly on either prediction accuracy or earliness, leading to sub-optimal interventions for at-risk students. This issue underlines the necessity for methods that effectively manage the trade-off between accuracy and earliness. Recognizing the limitations of existing methods, this study introduces a novel approach leveraging multi-objective reinforcement learning (MORL) to optimize the trade-off between prediction accuracy and earliness in SDP tasks. By framing SDP as a partial sequence classification problem, we model it through a multiple-objective Markov decision process (MOMDP), incorporating a vectorized reward function that maintains the distinctiveness of each objective, thereby preventing information loss and enabling more nuanced optimization strategies. Furthermore, we introduce an advanced envelope Q-learning technique to foster a comprehensive exploration of the solution space, aiming to identify Pareto-optimal strategies that accommodate a broader spectrum of preferences. The efficacy of our model has been rigorously validated through comprehensive evaluations on real-world MOOC datasets. These evaluations have demonstrated our model’s superiority, outperforming existing methods in achieving optimal trade-off between accuracy and earliness, thus marking a significant advancement in the field of SDP.

The current method of electricity stealing has changed from simple to high-tech. In this paper, combined with HPLC communication technology and measurement equipment, a three-layer progressive analysis model is established. The model fully exploits the advantages of HPLC in deepening application functions. Based on the edge computing resources and processing capabilities of the current electricity consumption information acquisition system, it realizes the identification of electricity theft behavior, the evaluation of user suspicion, the forensics of electricity theft, and the minute-level dispatch response to meet the actual power theft on site.

Interaction errors are hard to avoid in the process of human–robot interaction (HRI). User emotions toward interaction errors could further affect the user’s attitudes to robots and experiences of HRI and so on. In this regard, the present study explores the effects of different factors on user emotions when interaction errors occur in HRI. There is sparse research directly studying this perspective. In so doing, three factors, including robot feedback, passive and active contexts, and previous user emotions, were considered. Two stages of online surveys with 465 participants were implemented to explore attitudes to robots and the self-reporting of emotions in active and passive HRI. Then, a Yanshee robot was selected as the experimental platform, and 61 participants were recruited for a real human–robot empirical study based on the two surveys. According to the results of statistical analysis, we conclude some design guides can cope with scenarios of interaction errors. For example, feedback and previous emotions have impacts on user emotions after encountering interaction errors, but contexts do not. There are no interactive effects between the three factors. The approach to reduce negative emotions in the cases of interaction errors in HRI, such as providing irrelevant feedback and so on, is also illustrated in the contributions.

Yu-Syuan Wei,1 Yu-Liang Chen,2 Wei-Yun Li,1 Ya-Yi Yang,3 Sung-Jan Lin,4– 6 Ching-Ho Wu,7 Jiue-In Yang,8 Tse-En Wang,1 Jiashing Yu,2 Pei-Shiue Tsai1,3,4 1Graduate Institute of Veterinary Medicine, National Taiwan University, Taipei, 10617, Taiwan; 2Department of Chemical Engineering, College of Engineering, National Taiwan University, Taipei, 106, Taiwan; 3Department of Veterinary Medicine, National Taiwan University, Taipei, 10617, Taiwan; 4Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, 10617, Taiwan; 5Department of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, 10051, Taiwan; 6Department of Dermatology, National Taiwan University Hospital and College of Medicine, Taipei, 10002, Taiwan; 7Graduate Institute of Veterinary Clinical Science, School of Veterinary Medicine, National Taiwan University, Taipei, 10617, Taiwan; 8Department of Plant Pathology and Microbiology, National Taiwan University, Taipei, 10617, TaiwanCorrespondence: Jiashing Yu, Department of Chemical Engineering, College of Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Daan District, Taipei, 10617, Taiwan, Tel +886 2 33669477, Email jiayu@ntu.edu.tw Pei-Shiue Tsai, Department and Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Daan District, Taipei, 10617, Taiwan, Tel +886 2 33661290, Fax +886 2 23661475, Email psjasontsai@ntu.edu.twIntroduction: Cisplatin, a commonly used anticancer compound, exhibits severe off-target organ toxicity. Due to its wide application in cancer treatment, the reduction of its damage to normal tissue is an imminent clinical need. Cisplatin-induced testicular oxidative stress and damage lead to male sub- or infertility. Despite earlier studies showing that the natural polyphenol extracts honokiol serve as the free radical scavenger that reduces the accumulation of intracellular free radicals, whether honokiol exhibits direct effects on the testis and sperm is unclear. Thus, the aim of the current study is to investigate the direct effects of honokiol on testicular recovery and sperm physiology.Methods: We encapsulated this polyphenol antioxidation compound into liposome-based nanoparticles (nHNK) and gave intraperitoneally to mice at a dosage of 5 mg/kg body mass every other day for consecutive 6 weeks.Results: We showed that nHNK promotes MDC1-53bp1-associated non-homologous DNA double-strand break repair signaling pathway that minimizes cisplatin-induced DNA damage. This positive effect restores spermatogenesis and allows the restructuring of the multi-spermatogenic layers in the testis. By reducing mitochondrial oxidative damage, nHNK also protects sperm mitochondrial structure and maintains both testicular and sperm ATP production. By a yet-to-identify mechanism, nHNK restores sperm calcium influx at the sperm midpiece and tail, which is essential for sperm hypermotility and their interaction with the oocyte.Discussion: Taken together, the nanoparticulated antioxidant counteracts cisplatin-induced male fertility defects and benefits patients undertaking cisplatin-based chemotherapy. These data may allow the reintroduction of cisplatin for systemic applications in patients at clinics with reduced testicular toxicity.Keywords: nanomedicine, antioxidant, cisplatin, reproduction, DNA repair, polyphenol

Abstract Background The clinical presentation of adult-onset immunodeficiency with anti-interferon (IFN)-γ autoantibodies with intracellular pathogens can be highly variable, which can lead to misdiagnosis during the early stage of disease. Case presentation We report a complex case of a 54-year-old Chinese male who was human immunodeficiency virus-negative. He had a presence of anti-IFN-γ autoantibodies and suffered from various intracellular pathogenic infections. The patient was admitted to our hospital for the first time in July 2016 with severe pneumonia, and he experienced multiple pneumonia infections between 2017 and 2019. In March 2019, the patient was hospitalized due to pulmonary lesions and multiple-bone destruction. During hospitalization, the patient was confirmed to have disseminated Talaromyces marneffei infection and was successfully treated with antifungal therapy for 1 year. In June 2021, Mycobacterium kansasii infection was detected by positive culture and progressive bone destruction. A high concentration of anti-IFN-γ antibodies was observed in the patient’s serum. In addition, Listeria monocytogenes was isolated by blood culture, and the presence of L. monocytogenes in cerebrospinal fluid was confirmed by next-generation sequencing. Following anti-non-tuberculous mycobacteria (NTM) therapy and anti-bacterial therapy, the patient’s symptoms, pulmonary lesions, and bone destruction gradually improved. Conclusions Although the clinical presentation of adult-onset immunodeficiency with anti-IFN-γ autoantibodies can be highly variable, the diagnosis should be considered if patients suffer from unexplained repeated bacterial or opportunistic infections. Conventional and advanced molecular testing should be used, as needed, for microbiological diagnoses among this special immunodeficient population.

Alkaloid enantiomers have different physiological and pharmacological effects, and different chiral compositions have a large impact on cigarette sensory and use safety. Studying the effects of different configurations of alkaloid enantiomers on cigarette sensory is important for the development of tobacco products, but the chiral separation of alkaloid enantiomers has become the core problem. Here, the application of a C18 column coupled with a polysaccharide-based chiral column to separate and detect four pairs of alkaloid enantiomers in tobacco and cigarette smoke of different brands was investigated. Results showed that the tandem technology of the two columns enabled the baseline separation of four pairs of alkaloid enantiomers. The resolution of enantiomers of alkaloids in different tobacco samples differed in content and ratio, showing different chiral distribution characteristics. According to the different distribution characteristics of alkaloid enantiomers, tobacco samples of different brands can be distinguished and real cigarettes can be identified.

Abstract This study aims to give a new perspective to the biomarkers in the lung adenocarcinoma (LUAD) brain metastasis, pathways involved and potential therapeutics. We performed a comprehensive single-cell level transcriptomic analysis on one LUAD patient with circulating tumor cells (CTCs), primary tumor tissue and metastatic tumor tissue using scRNA-seq approach to identify metastasis related biomarkers. Further scRNA-seq were performed on 7 patients to validate the cancer metastatic hallmark. with single cells collected from either metastatic or primary LUAD tissues. Pathological and functional studies were also performed to evidence the critical role of RAC1 in the LUAD metastasis. Hallmark gene was verified based on immunohistochemistry staining, cytological experiment, survival information from The Cancer Genome Atlas (TCGA), and staining results from Human Protein Atlas (HPA) databases. PCA analysis revealed that CTCs were in the intermediate place between the metastatic group and primary group. In the unsupervised clustering analysis CTCs were closer to one of the metastatic tumor cells, implying heterogeneity of the metastatic tumor and origin of the CTCs were from metastatic site. Transitional phase related gene analysis identified RAC1 was enriched in metastatic tumor tissue (MTT) preferred gene set functioning as regulated cell death and apoptosis as well as promoted macromolecule organization. Compared with normal tissue, expression levels of RAC1 increased significantly in LUAD tissue based on HPA database. High expression of RAC1 predicts worse prognosis and higher-risk. EMT analysis identified the propensity of mesenchymal state in primary cells while epithelial signals were higher in the metastatic site. Functional clustering and pathway analyses suggested genes in RAC1 highly expressed cells played critical roles in adhesion, ECM and VEGF signaling pathways. Inhibition of RAC1 attenuates the proliferation, invasiveness and migration ability of lung cancer cells. Besides, through MRI T2WI results, we proved that RAC1 can promote brain metastasis in the RAC1-overexpressed H1975 cell burden nude mouse model. RAC1 and its mechanisms might promote drug design against LUAD brain metastasis.

Accurate and reliable pose estimation of boom-type roadheaders is the key to the forming quality of the tunneling face in coal mines, which is of great importance to improve tunneling efficiency and ensure the safety of coal mine production. The multi-laser-beam target-based visual localization method is an effective way to realize accurate and reliable pose estimation of a roadheader body. However, the complex background interference in coal mines brings great challenges to the stable and accurate segmentation and extraction of laser beam features, which has become the main problem faced by the long-distance visual positioning method of underground equipment. In this paper, a semantic segmentation network for underground laser beams in coal mines, RCEAU-Net, is proposed based on U-Net. The network introduces residual connections in the convolution of the encoder and decoder parts, which effectively fuses the underlying feature information and improves the gradient circulation performance of the network. At the same time, by introducing cascade multi-scale convolution in the skipping connection section, which compensates for the lack of contextual semantic information in U-Net and improves the segmentation effect of the network model on tiny laser beams at long distance. Finally, the introduction of an efficient multi-scale attention module with cross-spatial learning in the encoder enhances the feature extraction capability of the network. Furthermore, the laser beam target dataset (LBTD) is constructed based on laser beam target images collected from several coal mines, and the proposed RCEAU-Net model is then tested and verified. The experimental results show that, compared with the original U-Net, RCEAU-Net can ensure the real-time performance of laser beam segmentation while increasing the Accuracy by 0.19%, Precision by 2.53%, Recall by 22.01%, and Intersection and Union Ratio by 8.48%, which can meet the requirements of multi-laser-beam feature segmentation and extraction under complex backgrounds in coal mines, so as to further ensure the accuracy and stability of long-distance visual positioning for boom-type roadheaders and ensure the safe production in the working face.

Background: Both obstructive sleep apnea (OSA) and non-alcoholic fatty liver disease (NAFLD) are prevalent within obese individuals. We aimed to investigate the effects of intermittent hypoxia (IH), a clinical feature of OSA, on hepatic expression of fatty acid translocase (CD36) in relation to liver injury in lean and diet-induced obese mice. Methods: Four-week-old male C57BL/6J mice were randomized to standard diet (SD) or high fat (HF) diet groups. At 13-week-old, all mice were exposed to either air or IH (IH30; thirty hypoxic episodes per hour) for four weeks. We assessed liver injury through lipid profile, oxidative and inflammatory stress, histological scoring and hepatic CD36 expression. Results: In lean mice, IH elevated serum and hepatic triglyceride and free fatty acid (FFA) levels, in line with upregulation of hepatic CD36 expression and myeloperoxidase (MPO)-positive cells in support of inflammatory infiltrates along with increase in serum malondialdehyde (MDA), C-X-C motif chemokine ligand 1(CXCL-1) and monocyte chemoattractant protein-1 (MCP-1). In diet-induced obese mice, an increase in hepatic alanine transaminase (ALT) activity, serum and hepatic levels of lipid parameters and inflammatory markers, serum MDA level, hepatic expressions of CD36 and α-smooth muscle actin (α-SMA), and MPO-positive cells was observed. IH potentiated hepatic ALT activity, serum CXCL-1 and hepatic interleukin-6 (IL-6), in line with inflammatory infiltrates, but paradoxically, reduced hepatic FFA level and hepatic CD36 expression, compared to obese mice without IH exposure. However, IH further augmented diet-induced liver steatosis and fibrosis as shown by histological scores. Conclusion: This study contributes to support that IH featuring OSA may lead to liver injury via differential regulation of hepatic CD36 expression in lean and diet-induced obese mice.

In the power system with a high proportion of new energy access, the original electric vehicle charging operation mode of the distribution network will change, and the acceptance capacity of electric vehicles also needs to be re-evaluated. In this paper, an evaluation method for the acceptance capacity of electric vehicles is proposed for the distribution network with photovoltaic power generation system installed. Considering the random variation characteristics of the output of the photovoltaic power generation system, seasonal periodicity, and the influence of weather factors, an evaluation model is established. It uses the particle swarm optimization algorithm to calculate the number of electric vehicles that the photovoltaic power generation system can accept, and to analyze the acceptance capacity of the distribution network for electric vehicles. The method utilizes the photovoltaic output to fill the electric vehicle charging demand, and can realize the mutual consumption of the electric vehicle charging and the photovoltaic output.

With the widespread application of electric vehicles, the constant-power charging method that users can charge immediately makes the charging period of the vehicle coincide with the peak period of regular electricity consumption of the distribution network, which will cause the phenomenon of ”peak-on-peak” of the basic load of the power grid. In this paper, a variable power regulation charging optimization strategy is proposed, which takes the charging power and charging state of the electric vehicle in each period as the optimization variables, and uses the particle swarm algorithm to solve the charging strategy. Taking an office area as an example, the results show that the acceptance capacity is significantly improved when the variable power charging strategy is adopted.

Estimating structural connectivity from diffusion-weighted magnetic resonance imaging is a challenging task, partly due to the presence of false-positive connections and the misestimation of connection weights. Building on previous efforts, the MICCAI-CDMRI Diffusion-Simulated Connectivity (DiSCo) challenge was carried out to evaluate state-of-the-art connectivity methods using novel large-scale numerical phantoms. The diffusion signal for the phantoms was obtained from Monte Carlo simulations. The results of the challenge suggest that methods selected by the 14 teams participating in the challenge can provide high correlations between estimated and ground-truth connectivity weights, in complex numerical environments. Additionally, the methods used by the participating teams were able to accurately identify the binary connectivity of the numerical dataset. However, specific false positive and false negative connections were consistently estimated across all methods. Although the challenge dataset doesn’t capture the complexity of a real brain, it provided unique data with known macrostructure and microstructure ground-truth properties to facilitate the development of connectivity estimation methods.

Abstract Exploiting the spin degree of freedom to store and manipulate information provides a paradigm for future microelectronics. The development of van der Waals (vdW) heterostructures has created a fascinating platform for exploring spintronic properties in the two-dimensional (2D) limit. Transition-metal dichalcogenides such as tungsten diselenide (WSe2) have electronic band structures that are ideal for hosting many exotic spin–orbit phenomena. Here, we report the spin-filtering effect in all-vdW heterostructures with WSe2 barrier. Combining 2D-perpendicular magnetic anisotropy Fe3GeTe2 (FGT) with different thicknesses of WSe2, the FGT/WSe2/FGT spin valve shows distinct charge and spin transport behavior. Moreover, the negative magnetoresistance (−4.3%) could be inverted into positive magnetoresistance (up to +25.8%) with decreasing the WSe2 thickness. Furthermore, we proposed a spin-filtering model based on Δ-symmetry electrons tunneling to explain the crossover from negative to positive MR signal through ab initio calculation. These experimental and theoretical results illustrate the rich potential of the families of TMDC materials to control spin currents in 2D spintronic devices.

The zenith C-band frequency modulation continuous wave(C-FMCW) radar has good detection capability with high temporary-spatial resolution and large dynamic range. The Doppler spectral density data of two squall lines precipitation cases at Longmen of Guangdong are utilized to retrieve the air vertical velocity (Va) in clouds and droplet size distribution (DSD). The empirical relation method (checking relationship between mean particle falling velocity (Vt) and reflectivity factor) and the small-particle-trace method are explored to retrieve the air vertical velocity in clouds. And then the droplet size distribution is retrieved from the translated Doppler spectral density by a velocity-diameter relation. The retrieved DSD of two squall lines are then compared and validated with the observation of K-band micro rain radar and second-generation Parsivel disdrometer. The retrieved Va by the empirical relation method is slightly smaller for strong monomer than that by the small-particle-trace method and slightly larger for weak convective precipitation, but Vt is the opposite. The absolute value of Vt negative velocity by the empirical relation method and the small-particle-trace method corresponds to the moment of large particles and heavy rain observed by Parsivel disdrometer, indicating that Va of two methods is basically reliable. The comparison in DSD retrieval show that the number of small droplets observed by radar is higher, but Parsivel disdrometer may underestimate it. The results of the empirical relation method are closer to micro rain radar and Parsivel disdrometer when rain rate is below 1 mm·h-1. The medium droplets obtained by radar retrieval are consistent with Parsivel disdrometer measurements, but the concentration of large droplets is low when rain rate is stronger than 10 mm·h-1. The retrieval results of both methods are close to Parsivel disdrometer and micro rain radar when rain rate is between 1 mm·h-1 and 10 mm·h-1. The strong convection makes droplets rupture severer in the peak area of heavy precipitation in the squall line, resulting in smaller mass-weighted mean diameter (Dm) and larger generalized intercept parameter Nw of the empirical relation method and the small-particle-trace method retrieval. For weak convective precipitation at the back of the squall line, the value of empirical relation method is quite close to Parsivel disdrometer. Under different rain rate, μ value of C-FMCW radar is less than 10 and the fluctuation is smaller, indicating that the results of C-FMCW radar is even more reliable than Parsivel disdrometer and micro rain radar.

Objective To observe the effect of auricular acupoint sticking and pressing therapy on preventing postoperative nausea and vomiting in patients undergoing thoracolumbar surgery under general anesthesia. Methods To retrospectively analysis the clinical data of 126 patients who underwent posterior thoracolumbar surgery under general anesthesia, including 37 patients who underwent auricular point sticking and pressing 24 hours before surgery (group A), 48 patients who underwent auricular point sticking and pressing after surgery(group B) and 41 patients without auricular acupoint sticking and pressing therapy after operation (group C). Incidence of postoperative nausea and vomiting and PONV scores were recorded at 8 h, 24 h and 48 h after operation. Results Among the three groups of patients, group A had the lowest incidence of postoperative nausea and vomiting, and the lowest PONV score. The incidence of PONV at 48h after operation was 35. 13%, which was significantly lower than that in the group C(P

Abstract. Severe asthma is “asthma which requires treatment with high dose inhaled corticosteroids (ICS) plus a second controller (and/or systemic corticosteroids) to prevent it from becoming ‘uncontrolled’ or which remains ‘uncontrolled’ despite this therapy.” The state of control was defined by symptoms, exacerbations and the degree of airflow obstruction. Therefore, for the diagnosis of severe asthma, it is important to have evidence for a diagnosis of asthma with an assessment of its severity, followed by a review of comorbidities, risk factors, triggers and an assessment of whether treatment is commensurate with severity, whether the prescribed treatments have been adhered to and whether inhaled therapy has been properly administered. Phenotyping of severe asthma has been introduced with the definition of a severe eosinophilic asthma phenotype characterized by recurrent exacerbations despite being on high dose ICS and sometimes oral corticosteroids, with a high blood eosinophil count and a raised level of nitric oxide in exhaled breath. This phenotype has been associated with a Type-2 (T2) inflammatory profile with expression of interleukin (IL)-4, IL-5, and IL-13. Molecular phenotyping has also revealed non-T2 inflammatory phenotypes such as Type-1 or Type-17 driven phenotypes. Antibody treatments targeted at the T2 targets such as anti-IL5, anti-IL5Rα, and anti-IL4Rα antibodies are now available for treating severe eosinophilic asthma, in addition to anti-immunoglobulin E antibody for severe allergic asthma. No targeted treatments are currently available for non-T2 inflammatory phenotypes. Long-term azithromycin and bronchial thermoplasty may be considered. The future lies with molecular phenotyping of the airway inflammatory process to refine asthma endotypes for precision medicine.

Carbapenem resistance presents a major challenge for the global public health network, as clinical infections caused by carbapenem-resistant organisms (CRO) are frequently associated with significant morbidity and mortality. Ceftazidime–avibactam (CAZ–AVI) is a novel cephalosporin/β-lactamase inhibitor combination offering an important advance in the treatment of CRO infections. CAZ–AVI has been reported to inhibit the activities of Ambler classes A, C, and some class D enzymes. However, bacterial resistance has been emerging shortly after the introduction of this combination in clinical use, with an increasing trend. Understanding these resistance mechanisms is crucial for guiding the development of novel treatments and aiding in the prediction of underlying resistance mechanisms. This review aims to systematically summarize the epidemiology of CAZ–AVI-resistant strains and recently identified resistance mechanisms of CAZ–AVI, with a focus on the production of β-lactamase variants, the hyperexpression of β-lactamases, reduced permeability, and overexpressed efflux pumps. The various mechanisms of CAZ–AVI resistance that have emerged within a short timescale emphasize the need to optimize the use of current agents, as well as the necessity for the surveillance of CAZ–AVI-resistant pathogens.

Abstract Background Emerging mite-borne pathogens and associated disease burdens in recent decades are raising serious public health concerns, yet their distributions and ecology remain under-investigated. We aim to describe the geographical distributions of blood-sucking mites and mite-borne agents and to assess their ecological niches in China. Methods We mapped 549 species of blood-sucking mites belonging to 100 genera at the county level and eight mite-associated agents detected from 36 species of blood-sucking mites in China during 1978–2020. Impacts of climatic and environmental factors on the ecology of 21 predominant vector mites and a leading pathogen, Orientia tsutsugamushi, were assessed using boosted regression tree (BRT) models, and model-predicted risks were mapped. We also estimated the model-predicted number, area and population size of affected counties for each of the 21 mite species in China. Results Laelaps echidninus is the leading mite species that potentially affects 744 million people, followed by La. jettmari (517 million) and Eulaelaps stabularis (452 million). Leptotrombidium scutellare is the mite species harboring the highest variety of mite-borne agents including four Rickettsia species and two viruses, followed by Eu. stabularis (2 agents), L. palpale (2) and La. echidninus (2). The top two agents that parasitize the largest number of mite species are O. tsutsugamushi (28 species) and hantavirus (8). Mammalian richness, annual mean temperature and precipitation of the driest quarter jointly determine the ecology of the mites, forming four clusters of major mite species with distinct geographic distributions. High-risk areas of O. tsutsugamushi are mainly distributed in southern and eastern coastal provinces where 71.5 million people live. Conclusions Ecological niches of major mite species and mite-borne pathogens are much more extensive than what have been observed, necessitating expansion of current filed surveillance. Graphic Abstract

The purpose of this study is to predict sarcopenia by analyzing the composition of the gut microbiota.

Abstract. Acinetobacter baumannii is a frequent cause of nosocomial infections. Here we report an intermittent outbreak caused by the emerging carbapenem-resistant A. baumannii (CRAB) clone ST457 and assess the effectiveness of patient screening for outbreak control. CRAB isolates were collected from 74 patients admitted to the respiratory intensive care unit of a tertiary hospital between May 2018 and March 2019. Fourteen CRAB isolates were assigned to ST457, and 13 belonged to an outbreak clone, as determined by phylogenomic analysis. Strict patient screening was started at the respiratory intensive care unit on May 2019, through which a ST457-positive patient transferred from the intensive care unit was detected. No positive patients were detected within 3 months onwards. The results of this study highlight the importance of rigorous infection prevention and control measures, combined with patient screening, in controlling the CRAB outbreak.

Abstract Circular RNAs (circRNAs), continuous loops of single-stranded RNA, regulate gene expression during the development of various cancers. However, the function of circRNAs in hepatocellular carcinoma (HCC) is rarely discussed. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the mRNA levels of circ_0011385, miR-361-3p, and STC2 in 96 pairs of HCC tissues (tumor tissues and adjacent normal tissues), HCC cell lines, and L02 (human normal liver cell line) cells. The relationships between circ_0011385 expression and clinical features of HCC were evaluated. Functional experiments in vitro or in vivo were used to evaluate the biological function of circ_0011385. Bioinformatics analysis was performed to predict miRNAs and mRNAs sponged by circ_0011385. RNA immunoprecipitation (RIP) and dual-luciferase reporter gene assays were used to elucidate the interactions among circ_0011385, miR-361-3p, and STC2 (stanniocalcin 2). ChIP and dual-luciferase reporter gene assays were used to identify the upstream regulator of circ_0011385. High expression of circ_0011385 was observed in HCC tissues and cell lines and was significantly associated with tumor size, TNM stage, and prognosis. In addition, inhibition of circ_0011385 expression prevented the proliferation of HCC cells in vitro and in vivo. Circ_0011385 sponged miR-361-3p, thereby regulating the mRNA expression of STC2. In addition, the transcription of circ_0011385 was regulated by SP3. Circ_0011385 knockdown suppressed cell proliferation and tumor activity in HCC. Circ_0011385 may therefore serve as a new biomarker in the diagnosis and treatment of HCC.

Objective: Evaluation of the safety of WS series cooling agents for cigarettes. Methods: In this paper, pyrolysis-gas chromatography-mass spectrometry （Py-GC/MS） and thermogravimetric （TG） methods were used to study the pyrolysis behavior and content distribution of WS series cooling agents in tobacco under different atmospheres. Results: Through TG/DSC analysis, WS-3, WS-5, and WS-23 had only one obvious thermal weight loss stage, and the maximum weight loss rates occurred at 251.8, 281.6, and 206.5 ℃, respectively. The three cooling agents all showed sharp endothermic peaks before weight loss, and a phase transition process of melting occurred. It was speculated that it may be the transformation of crystal form or the dissolution of crystal. Under the atmosphere of 9% oxygen-containing nitrogen-oxygen mixture simulating cigarette combustion, the cracking products and quantities of the three cooling agents increased with the increase of temperature. In comparison, WS-3 and WS-23 were more stable, with less thermal cracking products, while WS-5 was less stable, the heat required for crystal transformation was the lowest and the heat required for complete weight loss was the least, and the thermal cracking products were relatively more. The thermal cracking results of the three cooling agents were mainly prototype transfer, and the normalized percentage content of the peak area of prototype transfer was above 99%. Conclusion: The three cooling agents, WS-3, WS-5, and WS-23, do not appear in the list of HPHCs or SVHC under heating conditions, and can be completely pyrolyzed before 350 ℃, they are all suitable as additives for heating cigarettes.

Since the first outbreak in the 19th century influenza virus has remained emergent owing to the huge pandemic potential. Only the pandemic of 1918 caused more deaths than any war in world history. Although two types of influenza– A (IAV) and B (IBV) cause epidemics annually, influenza A deserves more attention as its nature is much wilier. IAVs have a large animal reservoir and cause the infection manifestation not only in the human population but in poultry and domestic pigs as well. This many-sided characteristic of IAV along with the segmented genome gives rise to the antigenic drift and shift that allows evolving the new strains and new subtypes, respectively. As a result, the immune system of the body is unable to recognize them. Importantly, several highly pathogenic avian IAVs have already caused sporadic human infections with a high fatality rate (~60%). The current review discusses the promising strategy of using a potentially universal IAV mRNA vaccine based on conserved elements for humans, poultry, and pigs. This will better aid in averting the outbreaks in different susceptible species, thus, reduce the adverse impact on agriculture, and economics, and ultimately, prevent deadly pandemics in the human population.

Introduction: The combination of different agents used for procedural sedation allows a greater range of desirable effects while minimizing side effects. The ketamine-dexmedetomidine combination (ketadex) and ketamine-propofol combination (ketofol) are successful examples. The purpose of this meta-analysis was to compare the safety and efficacy of ketadex with ketofol used for procedural sedation in pediatric patients. Methods: We searched Pubmed, Cochrane Controlled Register of Trials, and Embase from inception to June 2022. Studies were independently evaluated for inclusion criteria and exclusion criteria by two reviewers. Outcome measures for safety comparison were the incidence of hypotension, bradycardia, respiratory depression, nausea, vomiting, and agitation; Outcome measure for efficacy comparison was clinicians' satisfaction. In addition, we compared the recovery time of ketadex and ketofol. Results: Nine studies were included in this meta-analysis. Compared with ketofol, ketadex sedation in pediatric patients had lower risk of respiratory depression (RR: 0.51, 95% CI: 0.34–0.76, P = 0.0009). However, ketadex displayed significant effect on recovery time (MD: 8.38 min, 95% CI: 7.55–9.22 min, P < 0.00001). Ketadex had similar incidence of hypotension (RR: 0.95, 95% CI: 0.33–2.67, P = 0.92) and bradycardia (RR: 1.80, 95% CI: 0.64–5.06, P = 0.26) compared to those with ketofol. Clinicians' satisfaction rate of ketadex and ketofol were both high (RR: 0.93, 95% CI: 0.69–1.25, P = 0.62). Also, no significant difference was observed between ketadex and ketofol on the incidence of nausea, vomiting, and agitation. Conclusions: Both ketadex and ketofol can provide effective sedation and maintain stable hemodynamics. In consideration of good safety profile in respiratory problems, we suggest ketadex is a better option for procedural sedation in pediatric patients.

Measurement(s) Distribution Technology Type(s) digital curation • Geographic Information System Factor Type(s) genus • species • province • city • county • GPS Sample Characteristic - Organism mite • Acari Sample Characteristic - Location China Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.14459055

BACKGROUND Hydride generation-atomic fluorescence spectroscopy (HG-AFS) is highly sensitive for the determination of trace selenium in geological samples. However, the complex matrix increases the analysis difficulty, especially owing to interference caused by organic carbon, complicated complexes, and coexisting ions in samples rich in organic matter and sulfides. Therefore, sample pretreatment is important. The use of conventional thiol cotton fiber (TCF) to enrich and separate selenium often leads to unstable recovery and premature saturation of the TCF when dealing with samples rich in organic matter and sulfides. OBJECTIVES To establish a method suitable for the determination of trace selenium in geological samples rich in organic matter and sulfides. METHODS For samples rich in organic matter, a double TCF column (mTCF=0.15g) was used to carry out adsorption twice. The recovery for high-sulfur geological samples could be increased either by increasing the amount of TCF (mTCF ≤ 0.2g) or reducing the sample amount. RESULTS The measurement results for the reference materials and actual samples showed that the optimized method satisfied the analysis requirements as selenium recoveries of >95.1% and >95.5% were achieved for the organic-rich and sulfide samples, respectively. Microwave digestion can effectively avoid the loss of selenium during digestion; the measured selenium content was consistent with that reported in the literature. CONCLUSIONS The improved method is suitable for geological samples rich in organic matter and sulfides, which can be used to determine trace selenium (ng/g to μg/g levels) in geological samples.

Auricularia polytricha possesses hypolipidemic effects and decreases lipid accumulation, leading to potential food additives for functional food processing. In this research, we explored the potential effects of A. polytricha noodles on hyperlipidemia and gut microbiota dysbiosis, and elucidated their possible regulatory mechanisms on lipid metabolism in high-fat diet (HFD) mice. A. polytricha noodles treatment significantly (P

Abstract Background Drought is one of the major environmental stresses resulting in a huge reduction in crop growth and biomass production. Pearl millet (Pennisetum glaucum L.) has excellent drought tolerance, and it could be used as a model plant to study drought resistance. The root is a very crucial part of plant that plays important roles in plant growth and development, which makes it a focus of research. Results In this study, we explored the mechanism of drought tolerance of pearl millet by comparing physiological and transcriptomic data under normal condition and drought treatment at three time points (1 h, 3 h and 7 h) in the root during the seedling stage. The relative electrical conductivity went up from 1 h to 7 h in both control and drought treatment groups while the content of malondialdehyde decreased. A total of 2004, 1538 and 605 differentially expressed genes were found at 1 h, 3 h and 7 h respectively and 12 genes showed up-regulation at all time points. Some of these differentially expressed genes were significantly enriched into ‘metabolic processes’, ‘MAPK signaling pathway’ and ‘plant hormone signal transduction’ such as the ABA signal transduction pathway in GO and KEGG enrichment analysis. Conclusions Pearl millet was found to have a quick drought response, which may occur before 1 h that contributes to its tolerance against drought stress. These results can provide a theoretical basis to enhance the drought resistance in other plant species.

Objective To explore the characteristics of 18F⁃fluoro⁃2⁃deoxy⁃D⁃glucose (18F⁃FDG) PET in Creutzfeldt⁃Jakob disease (CJD). Methods and Results The manifestations of 18F⁃FDG PET of 8 cases confirmed as CJD were analyzed retrospectively from August 2018 to January 2020. Five patients were male and 3 were female, with a mean age of (49.63±13.19) years. There were 7 sporadic CJD (sCJD) patients and one genetic CJD (gCJD) patient. All 8 patients were characterized by rapid progressive dementia. DWI hyperintensity in brain MRI were observed in all 8 patients. 18F⁃FDG PET analysis revealed frontal, parietal and temporal regions hypometabolism in all 8 cases. Occipital region hypometabolism was observed in 7 cases (7/8). For subcortical regions, hypometabolism were identified in thalamus (5/8), basal ganglia (3/8), brainstem (3/8) and cerebellum (3/8). Compared with the DWI hyperintensities, there were 40 hyperintense on DWI in the 50 cortical regions that were hypometabolic on 18F⁃FDG PET, especially in the frontal lobe. For subcortical regions, there were only 9 hyperintense on DWI in the 25 regions that were hypometabolic on 18F⁃FDG PET, especially the basal ganglia region. The brain stem and cerebellum hypometabolic regions showed no hyperintense on DWI. Conclusions The higher sensitivity of 18F⁃FDG PET is conducive to the differential diagnosis of CJD, especially in patients with rapid progression. 18F⁃FDG PET hypometabolism may indicate severe focal neurological impairment. The diagnosis of CJD should be considered for patients with rapidly progressive dementia accompanied with obvious symptoms of extra pyramidal system or cerebellum, cortical hypometabolism in 18F⁃FDG PET, and without obvious DWI hyperintensity.

KRAS gene mutation is widespread in tumors and plays an important role in various malignancies. Targeting KRAS mutations is regarded as the “holy grail” of targeted cancer therapies. Recently, multiple strategies, including covalent binding strategy, targeted protein degradation strategy, targeting protein and protein interaction strategy, salt bridge strategy, and multivalent strategy, have been adopted to develop KRAS direct inhibitors for anti-cancer therapy. Various KRAS-directed inhibitors have been developed, including the FDA-approved drugs sotorasib and adagrasib, KRAS-G12D inhibitor MRTX1133, and KRAS-G12V inhibitor JAB-23000, etc. The different strategies greatly promote the development of KRAS inhibitors. Herein, the strategies are summarized, which would shed light on the drug discovery for both KRAS and other “undruggable” targets.

Abstract Growing evidence demonstrates that MicroRNAs (miRNAs) play an essential role in contributing to tumor development and progression. However, the underlying role and mechanisms of miR-23b-5p in hepatocellular carcinoma (HCC) formation remain unclear. Our study showed that miR-23b-5p was downregulated in the HCC tissues and cell lines, and lower expression of miR-23b-5p was associated with more severe tumor size and poorer survival. Gain- or loss-of-function assays demonstrated that miR-23b-5p induced G0/G1 cell cycle arrest and inhibited cell proliferation both in vitro and in vivo. qRT-PCR, western blot and luciferase assays verified that Mammalian transcription factor Forkhead Box M1 (FOXM1), upregulated in HCC specimens, was negatively correlated with miR-23b-5p expression and acted as a direct downstream target of miR-23b-5p. In addition, miR-23b-5p could regulate cyclin D1 and c-MYC expression by directly targeting FOXM1. Further study revealed that restoration of FOXM1 neutralized the cell cycle arrest and cell proliferation inhibition caused by miR-23b-5p. Taken together, our findings suggest that miR-23b-5p acted as a tumor suppressor role in HCC progression by targeting FOXM1 and may serve as a potential novel biomarker for HCC diagnosis and prognosis.

Abstract Malignant T-cell-amplified sequence 1 (Mct-1) has been reported as an oncogene in multiple malignant diseases. However, the function of Mct-1 in hepatocellular carcinoma (HCC) and the molecular mechanisms underlying tumor progression have not been explored. In this study, Mct-1 expression levels in HCC tissues and cells were detected by quantitative real-time PCR and western blotting. Mct-1 shRNAs and overexpression vector were transfected into HCC cells to downregulate or upregulate Mct-1 expression. In vitro and in vivo assays were performed to investigate the function of Mct-1 in cell proliferation and apoptosis. RNA sequencing analysis (RNA-seq) was performed to explore differences in gene expression when silenced Mct-1 expression. Mct-1 was upregulated in HCC specimens and cell lines, and higher expression of Mct-1 was predictive of poor survival. Overexpression of Mct-1 was shown to promote cell proliferation and repress cell apoptosis both in vitro and in vivo. The results of RNA-seq indicated that knockdown of Mct-1 suppressed Yap expression, while the results of the luciferase assay also revealed that Mct-1 increases the activity of the Yap promoter. Restoration of Yap expression in Mct-1 knockdown cells partially recovered the promotion of cell proliferation and inhibition of apoptosis. Collectively, these results indicate that Mct-1 acts as a tumor promoter gene in HCC progression by up-regulating Yap expression and, thus, could serve a novel potential diagnostic and prognostic biomarker for HCC.

The scientific prediction of the TBM penetration rate is of great significance to the selection of hydraulic tunnel construction methods, construction schedule and cost estimation. In view of the high nonlinearity, fuzziness and complexity of TBM excavation process, and in order to improve the prediction accuracy and computational efficiency, the partial least squares regression (PLSR) has been applied to extract the principal components of the influencing parameters. Then the deep neural network (DNN) is employed to train and forecast the TBM penetration rate. A prediction model of TBM penetration rate based on the coupled method of PLSR and DNN is proposed. Based on the measured data of the double-shield TBM construction of a water conveyance tunnel in the Lanzhou water source construction project, six impact parameters including the rock uniaxial compressive strength, rock uniaxial tensile strength, cutter head thrust, cutter head speed, rock mass integrity coefficient and rock Cerchar abrasiveness index are selected to verify the prediction reasonability of the model. The fitting and prediction accuracy of the different prediction methods are compared and analyzed. The research results show that the PLSR can effectively overcome the problem of multiple collinearity between the independent variables. The extracted principal components are trained as the input layer of the DNN, which simplifies the structure of the neural network. The PLSR-DNN coupled model effectively avoids the over-fitting and inadequate fitting problems. It has the characteristics of fast convergence, stable solution and high fitting accuracy. The average relative fitting error of the PLSR-DNN prediction model is 2.96%, and the average relative prediction error is 3.27%. The fitting accuracy and prediction accuracy of the PLSR-DNN prediction model is significantly higher than those of PLSR model alone, BP neural network model and SVR model, respectively.