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Abstract Background A blood-based diagnostic test is a promising strategy for colorectal cancer (CRC). The MethyDT test (IColohunter), which detects methylation levels of NTMT1 and MAP3K14 -AS1, exhibited potential in discriminating CRC, but its clinical performance needs to be validated in large-scale populations. Methods A multicenter, double-blinded, cross-sectional study that enrolled 1194 participants was performed. Plasma samples were collected to detect methylation levels of NTMT1 and MAP3K14 -AS1 using quantitative methylation-specific PCR with the MethyDT test, and the accuracy was further evaluated by Sanger sequencing. Results The sensitivities of the MethyDT test for detecting CRC, early stages of CRC (I and II), advanced adenoma (AA), and high-grade intraepithelial neoplasia (HGIN) were 91.2% (95% confidence interval [CI], 88.4–94.0), 87.4% (95% CI, 82.5–92.2), 43.5% (95% CI, 35.7–51.4), and 72.7% (95% CI, 57.5–87.9), respectively. The specificities for participants with non-AA, interfering diseases (ID), and no evidence of disease (NED) were 85.0% (95% CI, 78.8–91.3), 93.7% (95% CI, 91.4–95.9) and 97.3% (95% CI, 90.5–99.7), respectively, and its overall specificity for all-controls was 92.4% (95% CI, 90.3–94.4). The consistency of the MethyDT test with pathology for CRC was high with a kappa value of 0.830 (95% CI, 0.795–0.865). Additionally, the MethyDT test was comparable to Sanger sequencing for detecting methylation with kappa values > 0.97. Conclusions The MethyDT test demonstrates excellent sensitivity and specificity for CRC and high consistency with Sanger sequencing for methylation, suggesting it may serve as a potential noninvasive diagnostic tool for the detection of CRC. Trial registration This clinical trial has been registered in ClinicalTrials.gov (NCT05508503).

Congenital muscular torticollis (CMT) is a more common childcare disease, which belongs to muscle-skeletal system diseases, and is more common in newborns. The disease is mainly due to congenital contracture due to chest locks, which leads to asymmetric head and neck. For such diseases, clear diagnosis and treatment in the early days is an important way to improve the prognosis of children. Compared with X-ray film, CT, and MRI, ultrasound examination has the advantages of low examination cost, short time, and no exposure to radiation during the examination. Moreover, ultrasound examination can provide an objective basis for the clinical diagnosis and prognosis evaluation of CMT children. This article reviews the latest research progress of conventional ultrasound, color Doppler ultrasound, and ultrasound elastography in the clinical diagnosis of CMT children and assisting in the formulation of treatment plans.

This paper presents the subsystem descriptions and testing of a small robotic platform intended to harvest strawberries that are grown on elevated beds in open field conditions. Agricultural robots can assist in the optimization of farm resources and help solve issues related to increasing farm costs and labor shortages. Monolithic, large size harvesters are already in development; however, they are susceptible to single-point-of-failure and lack the flexibility to adapt to varying field conditions and farm sizes. The proposed robotic harvester covers one row at a time and features a Delta arm configuration manipulator with a five-finger structure as the end-effector to individually pick strawberries. A deep neural network-based vision subsystem using a YOLOv4 model was adopted, which was configured to detect small objects and to locate and classify strawberries into five stages of maturity. During experiments on a commercial farm, the proposed platform, including vision, manipulation, and overbed navigation and control subsystems, achieved an overall success rate of 71.7% for five environment scenarios, with a minimum of 37.5% (the most complicated scenario) and a maximum of 94.0% (the easiest scenario). The average harvesting speed of the system was 7.5 s per strawberry.

ObjectiveAutonomous docking is the key to the cooperative operation of unmanned underwater vehicles (UUVs). However, due to environmental complexity and object characteristics, it is very difficult to achieve precise guidance and docking. In order to improve the accuracy and robustness of underwater docking, this study proposes a vision-guided docking scheme which encompasses vision processing and 3D trajectory tracking control. MethodsFirst, the overall vision-guided docking scheme is designed in combination with an analysis of task and object characteristics. Second, the YOLOv5 neural network is designed to complete the target detection of the underwater docking station, and the online measurement of the relative position and attitude relationship between the docking station and UUV is realized by an efficient perspective-n-point (EPnP) algorithm. Next, combined with the visual measurement results, an effective 3D robust trajectory tracking controller is designed on the basis of the 3D LOS guidance law, radial basis function neural network (RBFNN) and terminal sliding mode control (TSMC). Finally, the validity of the proposed scheme is verified through numerical simulation and a tank test. ResultsIn the tank test, the proposed vision-guided control algorithm can effectively complete the online detection and relative positioning of the underwater docking station, thereby achieving precise underwater docking. ConclusionThe results of this study show that the proposed vision-guided 3D trajectory tracking control scheme is reasonable and efficient, and can lay a good foundation for UUV docking.

Summary: Background: The causal associations of physical activity and sedentary behavior with the risk of gastrointestinal disease are unclear. We performed a Mendelian randomization analysis to examine these associations. Methods: Genetic instruments associated with leisure screen time (LST, an indicator of a sedentary lifestyle) and moderate-to-vigorous intensity physical activity (MVPA) at the genome-wide significance (P

Dysregulation of neurotransmitter metabolism in the central nervous system contributes to mood disorders such as depression, anxiety, and post–traumatic stress disorder. Monoamines and amino acids are important types of neurotransmitters. Our previous results have shown that disco-interacting protein 2 homolog A (Dip2a) knockout mice exhibit brain development disorders and abnormal amino acid metabolism in serum. This suggests that DIP2A is involved in the metabolism of amino acid–associated neurotransmitters. Therefore, we performed targeted neurotransmitter metabolomics analysis and found that Dip2a deficiency caused abnormal metabolism of tryptophan and thyroxine in the basolateral amygdala and medial prefrontal cortex. In addition, acute restraint stress induced a decrease in 5-hydroxytryptamine in the basolateral amygdala. Additionally, Dip2a was abundantly expressed in excitatory neurons of the basolateral amygdala, and deletion of Dip2a in these neurons resulted in hopelessness-like behavior in the tail suspension test. Altogether, these findings demonstrate that DIP2A in the basolateral amygdala may be involved in the regulation of stress susceptibility. This provides critical evidence implicating a role of DIP2A in affective disorders.

BackgroundHealth education about Helicobacter pylori (H. pylori) is one of the most effective methods to prevent H. pylori infection and standardize H. pylori eradication treatment. Short videos enable people to absorb and remember information more easily and are an important source of health education. This study aimed to assess the information quality of H. pylori-related videos on Chinese short video-sharing platforms.MethodsA total of 242 H. pylori-related videos from three Chinese short video-sharing platforms with the most users, TikTok, Bilibili, and Kwai, were retrieved. The Global Quality Score (GQS) and the modified DISCERN tool were used to assess the quality and content of videos, respectively. Additionally, comparative analyzes of videos based on different sources and common H. pylori issues were also conducted.ResultsThe median GQS score and DISCERN score was 2 for H. pylori-related videos analyzed in this study. Non-gastroenterologists posted the most H. pylori-related videos (136/242, 56.2%). Videos from gastroenterologists (51/242, 21.0%) had the highest GQS and DISCERN scores, with a median of 3. Few videos had content on family-based H. pylori infection control and management (5.8%), whether all H. pylori-positive patients need to undergo eradication treatment (27.7%), and the adverse effects of H. pylori eradication therapy (16.1%).ConclusionGenerally, the content and quality of the information in H. pylori-related videos were unsatisfactory, and the quality of the video correlated with the source of the video. Videos from gastroenterologists provided more correct guidance with higher-quality information on the prevention and treatment of H. pylori infection.

A plate-fin heat sink is usually used for the hot side of thermoelectric coolers. The plate-fin heat sink should be optimized to improve its heat dissipation capability and eventually elevate the thermoelectric cooler performance. In this paper, a heat dissipation model of the thermoelectric cooler hot side with a plate-fin sink is established, to explore the performances of the plate-fin sink with two types of fins (rectangular and V-type), two convective conditions (lateral and vertical) and three arrangements (single-row, double-row aligned, and double-row staggered). The results show that under vertical jet conditions, double-row aligned rectangular fins have the best heat dissipation capability for the thermoelectric cooler hot side. In order to optimize the fin geometry and maximize its overall performance, a multi-objective optimization of the fins was performed using a machine learning approach based on artificial neural networks (ANN) and non-dominated sorting genetic algorithm (NSGA-ІІ). The corresponding Pareto front is obtained and the technique for order preference by similarity to ideal solution (TOPSIS) method is applied to take the point. Compared with the base case at the same mass flow rate, the fins designed by this method resulted in a 23.3 % reduction in the mean temperature of the hot side.

Background China’s National Reimbursement Drug List (NRDL) has become the primary route for drug reimbursement in China. More recently, the authority has made pharmacoeconomic evaluation an integral part of the application for NRDL inclusion. The underlying financial conflict of interests (FCOI) of pharmacoeconomic evaluations, however, has the potential to influence evidence generated and thus subsequent decision-making yet remains poorly understood.Methods We searched for studies published between January 2012 and January 2022 on the 174 drugs added to the 2017–2020 NRDLs after successful negotiation. We categorised the study’s FCOI status into no funding, industry funding, non-profit funding and multiple fundings based on authors’ disclosure and assessed the reporting quality of included studies using the Consolidated Health Economic Evaluation Reporting Standards 2022 checklist. We compiled descriptive statistics of funding types and study outcomes using t-tests and χ2 tests and conducted multivariate regression analysis.Results We identified 378 records and our final sample included 92 pharmacoeconomic evaluations, among which 69.6% were conducted with at least one funding source. More than half (57.6%) of the evaluations reached favourable conclusions towards the intervention drug and 12.6% reached a dominant result of the intervention drug over the comparison from model simulation. The reporting quality of included studies ranged from 19 to 25 (on a scale of 28), with an average of 22.3. The statistical tests indicated that industry-funded studies were significantly more likely to conclude that the intervention therapy was economical (p

BackgroundLifestyle modification is the cornerstone of non-alcoholic fatty liver disease (NAFLD) prevention and treatment. Short video platforms can facilitate easier access to health information for patients, thereby influencing lifestyle changes. An increasing number of individuals rely on online platforms to acquire health-related information about NAFLD. However, the quality of information regarding NAFLD on these platforms remains unclear.ObjectiveThis study aimed to investigate the quality of information about NAFLD on TikTok.MethodsA total of 497 videos were retrieved from TikTok. The basic video information, including the video source, was extracted. Two independent raters evaluated the quality and reliability of the videos using the Global Quality Score system and a modified DISCERN tool. Propensity score matching (PSM) was used to compare video quality across sources.ResultsNAFLD-related videos on TikTok were divided into three groups according to the uploader: health professionals, medical institutions, and science bloggers. Overall, the quality of NAFLD videos on TikTok was not satisfactory. Before PSM, there were no significant differences in video quality or content between the three groups. After PSM, the quality of NAFLD videos from health professionals was significantly better than the videos created by other groups. Besides, the videos of health professionals outperformed those of medical institutions and science bloggers in terms of the definition of disease, risk factors, and treatment, but were inferior to those of medical institutions considering the symptoms and tests of NAFLD.ConclusionThe quality of NAFLD-related videos on TikTok needs improvement. Compared with videos created by science bloggers and medical institutions, videos from health professionals may provide accurate guidance on the treatment and prevention of NAFLD.

Abstract Background Patient-reported outcomes (PROs) can be obtained outside hospitals and are of great significance for evaluation of patients with chronic heart failure (CHF). The aim of this study was to establish a prediction model using PROs for out-of-hospital patients. Methods CHF-PRO were collected in 941 patients with CHF from a prospective cohort. Primary endpoints were all-cause mortality, HF hospitalization, and major adverse cardiovascular events (MACEs). To establish prognosis models during the two years follow-up, six machine learning methods were used, including logistic regression, random forest classifier, extreme gradient boosting (XGBoost), light gradient boosting machine, naive bayes, and multilayer perceptron. Models were established in four steps, namely, using general information as predictors, using four domains of CHF-PRO, using both of them and adjusting the parameters. The discrimination and calibration were then estimated. Further analyze were performed for the best model. The top prediction variables were further assessed. The Shapley additive explanations (SHAP) method was used to explain black boxes of the models. Moreover, a self-made web-based risk calculator was established to facilitate the clinical application. Results CHF-PRO showed strong prediction value and improved the performance of the models. Among the approaches, XGBoost of the parameter adjustment model had the highest prediction performance with an area under the curve of 0.754 (95% CI: 0.737 to 0.761) for death, 0.718 (95% CI: 0.717 to 0.721) for HF rehospitalization and 0.670 (95% CI: 0.595 to 0.710) for MACEs. The four domains of CHF-PRO, especially the physical domain, showed the most significant impact on the prediction of outcomes. Conclusion CHF-PRO showed strong prediction value in the models. The XGBoost models using variables based on CHF-PRO and the patient’s general information provide prognostic assessment for patients with CHF. The self-made web-based risk calculator can be conveniently used to predict the prognosis for patients after discharge. Clinical Trial Registration URL: http://www.chictr.org.cn/index.aspx ; Unique identifier: ChiCTR2100043337. Graphical abstract

Abstract No fully validated risk-stratification strategies have been established in China where colonoscopies resources are limited. We aimed to develop and validate a fecal immunochemical test (FIT)-based risk-stratification model for colorectal neoplasia (CN); 10,164 individuals were recruited from 175 centers nationwide and were randomly allocated to the derivation (n = 6776) or validation cohort (n = 3388). Multivariate logistic analyses were performed to develop the National Colorectal Polyp Care (NCPC) score, which formed the risk-stratification model along with FIT. The NCPC score was developed from eight independent predicting factors and divided into three levels: low risk (LR 0–14), intermediate risk (IR 15–17), and high risk (HR 18–28). Individuals with IR or HR of NCPC score or FIT+ were classified as increased-risk individuals in the risk-stratification model and were recommended for colonoscopy. The IR/HR of NCPC score showed a higher prevalence of CNs (21.8%/32.8% vs. 11.0%, P

BackgroundDietary management is considered a potential adjunctive treatment for inflammatory bowel disease (IBD). Short-video sharing platforms have enabled patients to obtain dietary advice more conveniently. However, accessing useful resources while avoiding misinformation is not an easy task for most patients. ObjectiveThis study aimed to evaluate the quality of the information in IBD diet–related videos on Chinese short-video sharing platforms. MethodsWe collected and extracted information from a total of 125 video samples related to the IBD diet on the 3 Chinese short-video sharing platforms with the most users: TikTok, Bilibili, and Kwai. Two independent physicians evaluated each video in terms of content comprehensiveness, quality (rated by Global Quality Score), and reliability (rated by a modified DISCERN tool). Finally, comparative analyses of the videos from different sources were conducted. ResultsThe videos were classified into 6 groups based on the identity of the uploaders, which included 3 kinds of medical professionals (ie, gastroenterologists, nongastroenterologists, and clinical nutritionists) and 3 types of non–medical professionals (ie, nonprofit organizations, individual science communicators, and IBD patients). The overall quality of the videos was poor. Further group comparisons demonstrated that videos from medical professionals were more instructive in terms of content comprehensiveness, quality, and reliability than those from non–medical professionals. Moreover, IBD diet–related recommendations from clinical nutritionists and gastroenterologists were of better quality than those from nongastroenterologists, while recommendations from nonprofit organizations did not seem to be superior to other groups of uploaders. ConclusionsThe overall quality of the information in IBD diet-related videos is unsatisfactory and varies significantly depending on the source. Videos from medical professionals, especially clinical nutritionists and gastroenterologists, may provide dietary guidance with higher quality for IBD patients.

Background and purpose: The latest RATIONALE-302 trial (NCT03430843) showed that tislelizumab therapy significantly improved overall survival benefits for patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) compared with traditional chemotherapy. This study aimed to compare the cost-effectiveness of tislelizumab versus chemotherapy as a second-line treatment for advanced or metastatic ESCC in China.Methods: A partitioned survival model was developed to predict patients’ lifetime quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) from the Chinese healthcare payers’ perspective. We extracted efficacy and safety data from the RATIONALE-302 trial and the local cost and resource use data from online databases and published studies. One-way sensitivity analysis (OWSA) and probabilistic sensitivity analysis (PSA) were performed to explore model uncertainty.Results: Compared with chemotherapy, tislelizumab generated a higher cost (US$ 10211.78 vs. US$ 7294.72) but yielded more QALY (0.78 vs. 0.51 QALYs). The ICER for tislelizumab was US$11073.85 per QALY gained. The PSA results indicated that the probability of tislelizumab being economical was 76% under a willingness-to-pay (WTP) threshold of 1.5 times per capita GDP ($17915) in China.Conclusion: Tislelizumab could be a promising cost-effective strategy as the second-line treatment for patients with ESCC compared with chemotherapy in the Chinese setting.

ABSTRACT Treatment of osteomyelitis is still challenging, as conventional antibiotic therapy is limited by the emergence of resistant strains and the formation of biofilms. Sonoantimicrobial chemotherapy (SACT) is a novel therapy of low-frequency and low-intensity ultrasound (LFLIU) combined with a sonosensitizer. Therefore, in our study, a sonosensitizer named emodin (EM) was proposed to be combined with LFLIU to relieve acute osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA) through antibacterial and antibiofilm effects. The efficiencies of different intensities of ultrasound, including single (S-LFLIU, 15 min) and multiple ultrasound (M-LFLIU, 3 times for 5 min at 4-h intervals), against bacteria and biofilms were compared, contributing to developing the best treatment regimen. Our results demonstrated that EM plus S-LFLIU or M-LFLIU (EM+S-LFLIU or EM+M-LFLIU) had significant combined bactericidal and antibiofilm effects, with EM+M-LFLIU in particular exhibiting superior antibiofilm performance. Furthermore, it was suggested that EM+M-LFLIU could produce a large amount of reactive oxygen species (ROS), destroy the integrity of the bacterial membrane and cell wall, and downregulate the expression of genes involved in oxidative stress, membrane wall synthesis, and bacterial virulence, as well as that of other related genes (agrB, pbp3, sgtB, gmk, zwf, and msrA). In vivo studies, micro-computed tomography (micro-CT), hematoxylin and eosin (H&E) staining, enzyme-linked immunosorbent assay (ELISA), and bacterial quantification of bone tissue indicated that EM+M-LFLIU could also relieve osteomyelitis due to MRSA infection. Our work proffers an original approach to bacterial osteomyelitis treatment that weakens drug-resistant bacteria and suppresses and degrades biofilm formation through SACT, which may provide new prospects for clinical treatment. IMPORTANCE Antibiotic therapy is the first choice for clinical treatment of osteomyelitis, but the formation of bacterial biofilms and the emergence of many drug-resistant strains also create an urgent need to find an alternative treatment to effectively eliminate the infection. Recently, LFLIU has come to be considered a safe and promising method of debridement and antibacterial therapy. In this study, we found that ultrasound and EM have a significant combined antibacterial effect in vivo and in vitro, which may play an antibacterial role by stimulating the production of ROS, destroying the bacterial cell wall, and inhibiting the expression of related genes. Our study expands the body of knowledge on the antibacterial effect of drugs—specifically emodin (EM)—through combined physiotherapy. If successfully integrated into clinical practice, these methods may reduce the burden of high concentrations of drugs needed to treat bacterial biofilms and avoid the growing resistance of bacteria to antibiotics.

ObjectiveDifferent forms of full coverage policy of essential medicines (FCPEMs) have been adopted worldwide to lower medication expenditure and improve adherence. This study aims to analyse the effect of FCPEMs on patients' medication adherence in Taizhou city, China.MethodsThis study was a quasi-experimental study and set treatment and control groups. We extracted Electronic Health Records (EHRs) for hypertension and diabetes 1 year before and after FCPEMs implementation and their medication adherence level assessed by physicians. We applied the propensity score matching (PSM) method to balance the bias between the two groups. Then, the descriptive analysis was used to compare the differences in the reported medication adherence. Using the Difference-In-Differences (DIDs) method, the fixed-effect model with the logistic regression was built to analyse the effects of FCPEMs.Results225,081 eligible patients were identified from the original database. In the baseline year, FCPEM covered 39,251 patients. After PSM, 6,587 patients in the treatment group and 10,672 patients in the control group remained. We found that the proportion of patients with high adherence in the treatment group increased by 9.1% (60.8 to 69.9%, P < 0.001) and that in the control group increased by 2.6% (62.5 to 65.2%, P < 0.001). The regression results showed that FCPEMs significantly increased patients' medication adherence (OR = 2.546, P < 0.001).ConclusionFCPEMs significantly improved medication adherence. Socially disadvantaged individuals might benefit more from continuing FCPEM efforts. Expanding the coverage of FCPEMs to other medicines commonly used in patients with chronic diseases may be a promising strategy to manage chronic diseases and promote patient outcomes.

Background and purpose: The TASTE trial indicated that patients with acute ischemic stroke (AIS) using edaravone dexborneol have a significantly higher proportion of 90-day good functional outcomes (mRS 0–1) than those using edaravone. This study compared the cost-effectiveness of the aforementioned interventions in treating AIS in the Chinese setting, aiming to inform treatment decisions in clinical practice.Methods: A model combining a decision tree and a Markov model was developed to assess the cost-effectiveness of edaravone dexborneol versus edaravone for AIS over a 30-year time horizon from the Chinese healthcare system’s perspective. Both efficacy and safety data were extracted from the TASTE study. Local costs and utilities were derived from publications and open-access databases; both cost and effectiveness were discounted at a rate of 5% per year. Sensitivity analyses were conducted to ensure robustness and identify the main drivers of the result.Results: Compared with edaravone, edaravone dexborneol for AIS was found to be cost-effective in the first year and highly cost-effective as the study time horizons extended. In the long term (30 years), edaravone dexborneol yielded a lifetime gain of 0.25 (0.07–0.45) quality-adjusted life years (QALYs) at an additional cost of CNY 2201.07 (-3,445.24–6,637.23), yielding an ICER of CNY 8823.41 per QALY gained under the willingness-to-pay (WTP) of 1.5 times per capita GDP (121,464 CNY). The result is robust in both deterministic and probabilistic sensitivity analysis (PSA) methods, with the advantage of the edaravone dexborneol strategy increasing over time. Specifically, the probability of edaravone dexborneol dominant dexborneol is 76.30%, 98.90%, and 99.50% over 1-, 5-, and 30-year time horizons.Conclusion: Both short- and long-term economic analyses suggest that edaravone dexborneol is highly likely to be a cost-effective alternative to treat AIS compared with edaravone in China.

Background: There has been growing evidence that the aberrantly expressed Homeobox-C 4 (HOXC4) plays crucial roles in the development of some cancer types. However, it remains unclear as far as its expression patterns and prognostic significance are concerned, as is tumor immunity.Methods: To investigate the expression levels and prognostic implications of HOXC4, multiple data sources were used in conjunction with quantitative real-time polymerase chain reaction (qRT-PCR) verification. Afterward, diverse immunological-related analyses, along with anti-cancer drug sensitivity, were performed in a number of cancer types. A further exploration of the underlying mechanisms of HOXC4 in tumorigenesis and immunity was carried out using the Gene Set Enrichment Analysis (GSEA) and the Gene Set Variation Analysis (GSVA).Results: Based on extensive database mining, HOXC4 was ubiquitously expressed across 21 tumor cell lines and significantly higher than that of normal tissues in 21 tumor types. The outcome of survival analysis including overall survival (OS), disease-free interval (DFI), disease-specific survival (DSS) and progression-free interval (PFI) revealed that upregulation of HOXC4 expression in several cancers was associated with worse prognosis. Additionally, HOXC4 was observed to correlate closely with colon adenocarcinoma (COAD), head and neck squamous cell carcinoma (HNSC), lower grade glioma (LGG), liver hepatocellular carcinoma (LIHC), rectum adenocarcinoma (READ), and thyroid carcinoma (THCA) in terms of tumor immune cells infiltration. As a result of our comprehensive pan-cancer study, we have identified a significant link between the expression of HOXC4 and the efficacy of immunotherapy-related treatments, together with anti-cancer drug sensitivity. As a final note, HOXC4 was found to modulate multiple signaling pathways involved in tumorigenesis and immunity.Conclusion: HOXC4 has been implicated in our study for the first time as an oncogene in cancers with a poor prognosis, potentially laying the groundwork for promising clinical biomarkers and immunotherapy approaches.

To address the search-and-docking problem in multi-stage prescribed performance switching (MPPS) scenarios, this paper presents a novel compound control method for three-dimensional (3D) underwater trajectory tracking control of unmanned underwater vehicles (UUVs) subjected to unknown disturbances. The proposed control framework can be divided into two parts: kinematics control and dynamics control. In the kinematics control loop, a novel parallel model predictive control (PMPC) law is proposed, which is composed of a soft-constrained model predictive controller (SMPC) and hard-constrained model predictive controller (HMPC), and utilizes a weight allocator to enable switching between soft and hard constraints based on task goals, thus achieving global optimal control in MPPS scenarios. In the dynamics control loop, a finite-time terminal sliding mode control (FTTSMC) method combining a finite-time radial basis function neural network adaptive disturbance observer (RBFNN-FTTSMC) is proposed to achieve disturbance estimation and fast convergence of velocity tracking errors. The simulation results demonstrate that the proposed PMPC-FTTSMC approach achieved an average improvement of 33% and 80% in the number of iterations compared with MPC with sliding mode control (MPC-SMC) and traditional MPC methods, respectively. Furthermore, the approach improved the speed of response by 35% and 44%, respectively, while accurately achieving disturbance observation and enhancing the system robustness.

Pancreatic adenosquamous carcinoma (ASPC) is a rare subtype of pancreatic cancer with lethal malignancy, and few studies have focused on the heterogeneity of ASPC. Here, we performed a single-cell sequencing procedure on pancreatic tumor tissue from an ASPC patient and a patient with high-grade intraductal papillary mucinous neoplasm (IPMN). Through the combined analysis of single-cell sequencing data from five pancreatic ductal adenocarcinoma (PDAC) patients, one IPMN patient, and one ASPC patient in a public database, we identified 11 main types of cells, including macrophages, B cells, cancer stem cells, ductal cells, fibroblasts, endo/stellate cells, neutrophils, acinar cells, T cells, natural killer (NK) cells, dendritic cells, and mast cells. Then, the different characteristics and differentiation paths of the immune microenvironment among IPMN, ASPC, and PDAC in macrophages, T cells, and cancer-associated fibroblasts (CAFs) were identified through multiple bioinformatics analyses. Two novel special cancer-associated fibroblasts were identified as nCAFs and imCAFs. Then, cancer cells in duct cells were identified using the infercnv software. Two ASPC-specific subgroups of cancer cells with squamous cell features were identified. Finally, the identified specific CAFs and cancer cells were mapped to TCGA-PAAD cohort through the cibersoftx software. All of these identified subgroups were calculated to have a significant prognostic value in pancreatic cancer patients. These findings will promote the clinical application of single-cell sequencing data of pancreatic cancer and deepen our understanding of ASPC.

Fibrinolytic enzymes are a kind of proteolytic enzymes that can hydrolyze fibrin and dissolve blood clots. They could be used as a therapeutic agent for treating thrombosis. It is important for the treatment of cardiovascular disease to find and develop new thrombolytic drugs. In order to explore new fibrinolytic enzymes, a strain named 214L-11 with protease and fibrinolytic enzyme activity, which was isolated from the Flaming Mountain of Xinjiang Province, was screened using the skimmed milk plate, the blood powder agarose plate and the fibrin plate methods. Phylogenetic analyses showed that strain 214L-11 shared the highest similarity with Streptomyces fumanus NBRC 13042T (98.88%), which indicated that it represented a potential novel species in the Streptomyces genus. The fibrinolytic enzyme produced by 214L-11 displayed thrombolytic and anticoagulant activities, and it could degrade a single specific protein in the thrombus, thereby destroying the thrombus structure. The fermentation medium optimized through response surface methodology was 15 g/L soluble starch, g/L KNO3 0.58, 0.43 g/L peptone, 0.01 g/L FeSO4·7H2O, 0.5 g/L MgSO4·7H2O, 0.2 g/L Mn2+, 0.5 g/L NaCl and 1 L distilled water, pH 8, and the maximum amount of fibrinolytic enzyme produced by strain 214L-11 in the optimal fermentation medium was 1255.3 FU/mL. Overall, the fibrinolytic enzyme-producing strain was screened from the Flaming Mountain of Xinjiang for the first time, which provided a basis for further research and the development of new efficient and safe hemolytic drugs.

In this work, bacterial community composition and actinobacteria resources were explored in extremely hot and hyper-arid areas of Flaming Mountain. This was achieved through a combination of PCR amplicon sequencing of bacterial 16S rRNA gene and cultivation-dependent isolation and characterization efforts. According to the high-throughput sequencing results and soil characteristics, 11 kinds of media were firstly designed to isolate actinobacteria, following the screening and identification of related strains. The results showed that a total of 2994 operational taxonomic units (OTUs) were obtained, involving 22 phyla, 77 orders and 121 genera. Among them, actinobacteria with the relative abundance of 8% ranked third, accounting for 33 genera and 47 species. A total of 132 strains distributed by eight families and 11 genera of actinobacteria were isolated from 11 media, of which six strains were potential new species. Furthermore, the functional characteristics of isolated strains were preliminarily evaluated. The results showed that the obtained strains generally had tolerance against heat, salt and alkali. Fifty-two strains had antibacterial activity, 69 strains could produce hydrolases, and 12.4% of the strains had quorum sensing inhibitory activity. The present study has laid a solid foundation for further understanding the bacterial diversity and exploiting actinobacteria resources in the Flaming Mountain area.

Precise canopy management is critical in vineyards for premium wine production because maximum crop load does not guarantee the best economic return for wine producers. The growers keep track of the number of grape bunches during the entire growing season for optimizing crop load per vine. Manual counting of grape bunches can be highly labor-intensive and error prone. Thus, an integrated, novel detection model, Swin-transformer-YOLOv5, was proposed for real-time wine grape bunch detection. The research was conducted on two varieties of Chardonnay and Merlot from July to September 2019. The performance of Swin-T-YOLOv5 was compared against commonly used detectors. All models were comprehensively tested under different conditions, including two weather conditions, two berry maturity stages, and three sunlight intensities. The proposed Swin-T-YOLOv5 outperformed others for grape bunch detection, with mean average precision (mAP) of up to 97% and F1-score of 0.89 on cloudy days. This mAP was ~44%, 18%, 14%, and 4% greater than Faster R-CNN, YOLOv3, YOLOv4, and YOLOv5, respectively. Swin-T-YOLOv5 achieved an R2 of 0.91 and RMSE of 2.4 (number of grape bunches) compared with the ground truth on Chardonnay. Swin-T-YOLOv5 can serve as a reliable digital tool to help growers perform precision canopy management in vineyards.