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Abstract Background Patients-derived xenograft (PDX) model have been widely used for tumor biological and pathological studies. However, the metabolic similarity of PDX tumor to the primary cancer (PC) is still unknown. Methods In present study, we established PDX model by engrafting primary tumor of pancreatic ductal adenocarcinoma (PDAC), and then compared the tumor metabolomics of PC, the first generation of PDX tumor (PDXG1), and the third generation of PDX tumor (PDXG3) by using 1H NMR spectroscopy. Then, we assessed the differences in response to chemotherapy between PDXG1 and PDXG3 and corresponding metabolomic differences in drug-resistant tumor tissues. To evaluate the metabolomic similarity of PDX to PC, we also compared the metabolomic difference of cell-derived xenograft (CDX) vs. PC and PDX vs. PC. Results After engraftment, PDXG1 tumor had a low level of lactate, pyruvate, citrate and multiple amino acids (AAs) compared with PC. Metabolite sets enrichment and metabolic pathway analyses implied that glycolysis metabolisms were suppressed in PDXG1 tumor, and tricarboxylic acid cycle (TCA)-associated anaplerosis pathways, such as amino acids metabolisms, were enhanced. Then, after multiple passages of PDX, the altered glycolysis and TCA-associated anaplerosis pathways were partially recovered. Although no significant difference was observed in the response of PDXG1 and PDXG3 to chemotherapy, the difference in glycolysis and amino acids metabolism between PDXG1 and PDXG3 could still be maintained. In addition, the metabolomic difference between PC and CDX models were much larger than that of PDX model and PC, indicating that PDX model still retain more metabolic characteristics of primary tumor which is more suitable for tumor-associated metabolism research. Conclusions Compared with primary tumor, PDX models have obvious difference in metabolomic level. These findings can help us design in vivo tumor metabolomics research legitimately and analyze the underlying mechanism of tumor metabolic biology thoughtfully.

Abstract Background Double-balloon enteroscopy (DBE) is a standard method for diagnosing and treating small bowel disease. However, DBE may yield false-negative results due to oversight or inexperience. We aim to develop a computer-aided diagnostic (CAD) system for the automatic detection and classification of small bowel abnormalities in DBE. Design and methods A total of 5201 images were collected from Renmin Hospital of Wuhan University to construct a detection model for localizing lesions during DBE, and 3021 images were collected to construct a classification model for classifying lesions into four classes, protruding lesion, diverticulum, erosion & ulcer and angioectasia. The performance of the two models was evaluated using 1318 normal images and 915 abnormal images and 65 videos from independent patients and then compared with that of 8 endoscopists. The standard answer was the expert consensus. Results For the image test set, the detection model achieved a sensitivity of 92% (843/915) and an area under the curve (AUC) of 0.947, and the classification model achieved an accuracy of 86%. For the video test set, the accuracy of the system was significantly better than that of the endoscopists (85% vs. 77 ± 6%, p

BackgroundExtensive research has been conducted on the correlation between adipose tissue and the risk of malignant lymphoma. Despite numerous observational studies exploring this connection, uncertainty remains regarding a causal relationship between adipose tissue and malignant lymphoma.MethodsThe increase or decrease in adipose tissue was represented by the height of BMI. The BMI and malignant lymphoma genome-wide association studies (GWAS) used a summary dataset from the OPEN GWAS website. Single-nucleotide polymorphisms (SNPs) that met the criteria of P 0.8 were identified, while palindromic and outlier SNPs were excluded. Mendelian randomization (MR) analysis used five methods, including inverse-variance weighted (IVW) model, weighted median (WM), MR-Egger, simple mode, and weighted mode. Sensitivity assessments included Cochran’s Q test, MR-Egger intercept test, and leave-one-out analysis. Participants randomly selected by the National Center for Health Statistics (NHANSE) and newly diagnosed HL patients at Fujian Medical University Union Hospital were used for external validation.ResultsThe results of the MR analysis strongly supported the causal link between BMI and Hodgkin’s lymphoma (HL). The research demonstrated that individuals with lower BMI face a significantly increased risk of developing HL, with a 91.65% higher risk (ORIVW = 0.0835, 95% CI 0.0147 – 0.4733, P = 0.005). No signs of horizontal or directional pleiotropy were observed in the MR studies. The validation results aligned with the results from the MR analysis (OR = 0.871, 95% CI 0.826 – 0.918, P< 0.001). And there was no causal relationship between BMI and non-Hodgkin’s lymphoma (NHL).ConclusionsThe MR analysis study demonstrated a direct correlation between lower BMI and HL. This suggested that a decrease in adipose tissue increases the risk of developing HL. Nevertheless, further research is essential to grasp the underlying mechanism of this causal association comprehensively.

Abstract Background Lifestyle change plays a crucial role in the prevention and treatment of metabolic dysfunction-associated steatotic liver disease (MASLD). In recent years, diet soft drinks that emphasize “zero sugar and zero calories” have become all the rage, but whether diet soft drink consumption is associated with MASLD is not clear. Methods This study included data from the National Health and Nutrition Examination Surveys (NHANES) in 2003–2006. The assessment of MASLD status primarily relied on the Fatty Liver Index (FLI). Weighted multiple Logistic regression models were constructed to evaluate the association between diet soft drink consumption and MASLD. Additionally, mediation analysis was performed to examine the mediating effect of body mass index (BMI). Results A total of 2,378 participants were included in the study, among which 1,089 individuals had MASLD, and the weighted prevalence rate was 43.64%. After adjusting for variables related to demographic, lifestyle, and metabolic syndrome, excessive diet soft drink consumption (the “always” frequency) remained significantly associated with the occurrence of MASLD (OR = 1.98, 95%CI = 1.36–2.89, P = 0.003). It was estimated that 84.7% of the total association between diet soft drink consumption and MASLD was mediated by BMI (P

Recent studies confirmed that pyroptosis is involved in the progression of pulmonary hypertension (PH), which could promote pulmonary artery remodeling. Urolithin A (UA), an intestinal flora metabolite of ellagitannins (ETs) and ellagic acid (EA), has been proven to possess inhibitory effects on pyroptosis under various pathological conditions. However, its role on PH remained undetermined. To investigate the potential of UA in mitigating PH, mice were exposed to hypoxia (10% oxygen, 4 weeks) to induce PH, with or without UA treatment. Moreover, in vitro experiments were carried out to further uncover the underlying mechanisms. The in vivo treatment of UA suppressed the progression of PH via alleviating pulmonary remodeling. Pyroptosis-related genes were markedly upregulated in mice models of PH and reversed after the administration of UA. In accordance with that, UA treatment significantly inhibited hypoxia-induced pulmonary arterial smooth muscle cell (PASMC) pyroptosis via the AMPK/NF-κB/NLRP3 pathway. Our results revealed that UA treatment effectively mitigated PH progression through inhibiting PASMC pyroptosis, which represents an innovative therapeutic approach for PH.

Bone marrow-derived CD34-positive (CD34+) endothelial progenitor cells (EPCs) has unique functions in the mechanism of compensatory lung growth (CLG). The content of this study is mainly to describe the effect of microRNA (miR)-155 in the mechanisms of EPCs and CLG. Our study found that transfection of miR-155 mimic could promote EPC proliferation, migration and tube formation, while transfection of miR-155 inhibitor had the opposite effect. It was also found that transfection of pc-JARID2 inhibited EPC proliferation, migration and tube formation, while transfection of si-JARID2 had the opposite effect. miR-155 can target and negatively regulate JARID2 expression. Overexpression of JARID2 weakened the promoting effects of miR-155 mimic on EPC proliferation, migration, and tubular formation, while silencing JARID2 weakened the inhibitory effects of miR-155 inhibitors on EPC proliferation, migration, and tubular formation. Transplantation of EPCs transfected with miR-155 mimic into the left lung model effectively increased lung volume, total alveolar number, diaphragm surface area, and lung endothelial cell number, while transplantation of EPCs co-transfected with miR-155 mimic and pc-JARID2 reversed this phenomenon. Overall, we found that miR-155 activates CD34+ EPC by targeting negative regulation of JARID2 and promotes CLG.

Recently, several novel medications, such as Ustekinumab, Infliximab, and Vedolizumab, have emerged as potential options for inflammatory bowel disease(IBD) management. Despite achieving some effects in clinical applications, these therapies are still plagued by inadequate response rates and adverse side effects. With rapid progress in immunological research, therapeutic vaccines are gaining traction as an alternative. These vaccines aim to activate the body’s immune system to generate specific antibodies, thereby offering a potential avenue for treating IBD. The efficacy and safety of vaccines, coupled with their potential to mitigate the financial and healthcare burden associated with disease treatment, render therapeutic vaccines a more favorable approach for managing patients with IBD. In this review, we critically examine the existing literature pertaining to therapeutic vaccines for IBD, aiming to offer researchers a comprehensive understanding of their applications and prospects and stimulate novel vaccine development by presenting innovative ideas in this field.

Herein, network pharmacology was used to identify the active components in Ilex kudingcha and common hypertension-related targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted, and molecular docking was performed to verify molecular dynamic simulations. Six active components in Ilex kudingcha were identified; furthermore, 123 target genes common to hypertension were identified. Topological analysis revealed the strongly associated proteins, with RELA, AKT1, JUN, TP53, TNF, and MAPK1 being the predicted targets of the studied traditional Chinese medicine. In addition, GO enrichment analysis revealed significant enrichment of biological processes such as oxidative stress, epithelial cell proliferation, cellular response to chemical stress, response to xenobiotic stimulus, and wound healing. Furthermore, KEGG enrichment analysis revealed that the genes were particularly enriched in lipid and atherosclerosis, fluid shear stress and atherosclerosis, and other pathways. Molecular docking revealed that the key components in Ilex kudingcha exhibited good binding potential to the target genes RELA, AKT1, JUN, TP53, TNF, and IL-6. Our study results suggest that Ilex kudingcha plays a role in hypertension treatment by exerting hypolipidemic, anti-inflammatory, and antioxidant effects and inhibiting the transcription of atherosclerosis-related genes.

The linking of ethacrynic acid with ethylenediamine and 1,4-butanediamine gave EDEA and BDEA, respectively, as membrane-permeable divalent pro-inhibitors of glutathione S-transferase (GST). Their divalent glutathione conjugates showed subnanomolar inhibition and divalence-binding to GSTmu (GSTM) (PDB: 5HWL) at ∼0.35 min−1. In cisplatin-resistant SK-OV-3, COC1, SGC7901 and A549 cells, GSTM activities probed by 15 nM BDEA or EDEA revealed 5-fold and 1.0-fold increases in cisplatin-resistant SK-OV-3 and COC1 cells, respectively, in comparison with the susceptible parental cells. Being tolerable by HEK293 and LO2 cells, BDEA at 0.2 μM sensitised resistant SK-OV-3 and COC1 cells by ∼3- and ∼5-folds, respectively, released cytochrome c and increased apoptosis; EDEA at 1.0 μM sensitised resistant SK-OV-3 and A549 cells by ∼5- and ∼7-fold, respectively. EDEA at 1.7 μg/g sensitised resistant SK-OV-3 cells to cisplatin at 3.3 μg/g in nude mouse xenograft model. BDEA and EDEA are promising leads for probing cellular GSTM and sensitising cisplatin-resistant ovarian cancers.

BackgroundEndoplasmic reticulum stress (ERS) is a critical factor in the development of ulcerative colitis (UC); however, the underlying molecular mechanisms remain unclear. This study aims to identify pivotal molecular mechanisms related to ERS in UC pathogenesis and provide novel therapeutic targets for UC.MethodsColon tissue gene expression profiles and clinical information of UC patients and healthy controls were obtained from the Gene Expression Omnibus (GEO) database, and the ERS-related gene set was downloaded from GeneCards for analysis. Weighted gene co-expression network analysis (WGCNA) and differential expression analysis were utilized to identify pivotal modules and genes associated with UC. A consensus clustering algorithm was used to classify UC patients. The CIBERSORT algorithm was employed to evaluate the immune cell infiltration. Gene Set Variation Analysis (GSVA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to explore potential biological mechanisms. The external sets were used to validate and identify the relationship of ERS-related genes with biologics. Small molecule compounds were predicted using the Connectivity Map (CMap) database. Molecular docking was performed to simulate the binding conformation of small molecule compounds and key targets.ResultsThe study identified 915 differentially expressed genes (DEGs) and 11 ERS-related genes (ERSRGs) from the colonic mucosa of UC patients and healthy controls, and these genes had good diagnostic value and were highly correlated. Five potential small-molecule drugs sharing tubulin inhibitors were identified, including albendazole, fenbendazole, flubendazole, griseofulvin, and noscapine, among which noscapine exhibited the highest correlation with a high binding affinity to the targets. Active UC and 10 ERSRGs were associated with a large number of immune cells, and ERS was also associated with colon mucosal invasion of active UC. Significant differences in gene expression patterns and immune cell infiltration abundance were observed among ERS-related subtypes.ConclusionThe results suggest that ERS plays a vital role in UC pathogenesis, and noscapine may be a promising therapeutic agent for UC by affecting ERS.

A humanoid robot is an advanced representation of robot techniques. It can move like a human and possesses the ability to use human tools. Sensing and intelligent control technologies have increased the intelligence of humanoid robots. However, the dexterity of a humanoid robot is still far from that of a human. Herein, a bending sensor is introduced to detect human motion, which can thus be digitized to enable a humanoid robot to learn to be more dexterous. This bending sensor is fabricated of carbon fiber with a cascade structure, resulting in excellent characteristics, including a quantitative detection capability, high gauge factor, low hysteresis, long‐term durability, and high‐frequency response. Thus, the bending sensor can recognize both the large‐scale motion of joint bending and subtle motion of muscle contraction. Fourteen bending sensors corresponding to the 14 knuckles of the human hand can accurately recognize and digitize hand gestures. These multichannel sensors are combined with nine additional bending sensors to comprehensively digitize the grasping process of the upper limb and recognize the grasping of objects with different sizes and weights. These successful applications demonstrate that the bending sensor can open a path toward learning human behavior for a humanoid robot.

AimsWe conducted bibliometric and visualization analyses to evaluate the current research status, hotspots, and trends related to the human microbiota markers in colorectal cancer screening.MethodsThe related studies were acquired from the Web of Science Core Collection (WoSCC) database on 5 January 2023. Analyses of the co-occurrence and cooperation relationships between the cited authors, institutions, countries/regions, cited journals, cited articles, and keywords in the studies were carried out using CiteSpace 5.8.R3 software and the Online Analysis platform of Literature Metrology. Additionally, relevant knowledge graphs were drawn to perform visualization analyses; a keywords cluster analysis and a burst analysis were also conducted.ResultsAfter analyzing 700 relevant articles, this bibliometric analysis found that the annual publications showed an increasing trend from 1992 to 2022. Yu Jun from the Chinese University of Hong Kong had the highest cumulative number of publications, whereas Shanghai Jiao Tong University was the most productive institution. China and the USA have contributed the largest number of studies. The keywords frequency analysis demonstrated that “colorectal cancer,” “gut microbiota,” “Fusobacterium nucleatum,” “risk,” and “microbiota” were the most frequent keywords, and the keywords cluster analysis found that the current hotspots were as follows: (a) the precancerous lesions of colorectal cancer (CRC) that need to be screened, such as inflammatory bowel disease (IBD) and advanced adenoma, (b) the gut-derived microbiome for CRC screening, and (c) the early detection of CRC. The burst analysis further showed that the combination of microbiomics with metabolomics might be the future research trend in the field of CRC screening.ConclusionThe findings of the current bibliometric analysis firstly provide an insight into the current research status, hotspots, and future trends in the field of CRC screening based on the microbiome; the research in this field is becoming more in-depth and diversified. Some human microbiota markers, especially “Fusobacterium nucleatum,” are promising biomarkers in CRC screening, and a future hotspot might be the combined analysis of microbiomics and metabolomics for CRC risk screening.

Mites have been a persistent infectious disease affecting both humans and animals since ancient times. In veterinary clinics, the primary approach for treating and managing mite infestations has long been the use of chemical acaricides. However, the widespread use of these chemicals has resulted in significant problems, including drug resistance, drug residues, and environmental pollution, limiting their effectiveness. To address these challenges, researchers have shifted their focus towards natural products that have shown promise both in the laboratory and real-world settings against mite infestations. Natural products have a wide variety of chemical structures and biological activities, including acaricidal properties. This article offers a comprehensive review of the acaricidal capabilities and mechanisms of action of natural products like plant extracts, natural compounds, algae, and microbial metabolites against common animal mites.

The variation in aerodynamic parameters during the process of a variable sweepback hybrid aerial underwater vehicle (HAUV) affects flight stability. During the air–water trans-media locomotion, there are medium mutations and solid–liquid gas coupling phenomena, resulting in the complex dynamic process of HAUV. To ensure stable control during the trans-media process of a variable sweepback vehicle, this study proposes a neural-network-based adaptive dynamic surface control method for aircraft flight-path angle. This method aims to establish an effective control model for the entire process of air to media transition, in response to the characteristics of uncertainty and external disturbances in the process of variable backsweeping in the air and media transition. By utilizing the multibody dynamics method, the dynamic equations for variable-swept vehicles are established and transformed into a rigorous feedback system with model uncertainty. The adaptive dynamic surface method in this paper introduces a first-order filter, which overcomes the “differential explosion” problem in traditional backstepping control design through differential filtering; the unknown parameters present in the model are estimated online through adaptive laws, and the uncertain parts of the system are overcome through nonlinear damping items. By analyzing Lyapunov stability, the semi-global stability of the required closed-loop system can be obtained, and adjusting the controller parameters can make the tracking error infinitely small. Numerical simulations are conducted to illustrate the tracking control of flight-path angles for different plunge-diving angle rates and strategy of ingress. The results show that HAUV with variable-swept configuration with different strategy has a great effect on the stability of plunge-diving locomotion; the designed controller can effectively track the target trajectory and has a certain degree of robustness and adaptability.

The development of hybrid unmanned aerial underwater vehicles (HAUVs) compatible with the advantages of the aerial vehicles and the underwater vehicles is of great significance. This paper presents the first study on a new HAUV layout using four rotors to realize the medium crossing motion of a transverse slender body similar to the fuselage of a missile or a submarine, that is, the hybrid aerial underwater quadrotor (HAUQ). Then, a robust control strategy is proposed for the take-off HAUQ on the water in the presence of unknown disturbances and complex model dynamic uncertainties. As a semi-submersible HAUQ rises straight from the water, the inside of the slender fuselage placed horizontally is filled with water. The center of the mass, the moment of inertia, and the arm of the force of the HAUQ will change rapidly in the take-off phase from the water because of the rapid nonuniform change in mass caused by the passive fast drainage. It is difficult to establish an accurate mathematical model of the complex dynamic changes caused by the multi-media dynamics, the fast changing buoyancy, and the added mass crossing the air–water surface. Therefore, an uncertain kinematic and dynamic model is established through the passive, fast, nonuniform change and the complex dynamics are considered as the unknown terms, and the external disturbances of gust and other factors are assumed as the bounded disturbance input. A robust design approach is introduced to deal with the fast time-varying mass disturbance based on the input-to-state stability (ISS) theorem. The complex dynamics are estimated using the basis function and the unknown weight parameters, and the adaptive laws are adopted for the on-line estimation of the unknown weight parameters. Considering the residual disturbance of the uncertain nonlinear system as a total disturbance term, a disturbance observer is introduced for disturbance observation. The numerical simulation shows the feasibility and robustness of the proposed algorithm.

Aims: This study aimed to analyze the related research on the influence of dietary patterns on IBD carried out over the past 30 years to obtain the context of the research field and to provide a scientific basis and guidance for the prevention and treatment of IBD. Methods: The literature on the effects of dietary patterns on inflammatory bowel disease published over the past three decades was retrieved from the Web of Science Core Collection (WoSCC) database. CiteSpace, VOSviewer, the R software (version 4.3.0) bibliometrix package, the OALM platform, and other tools were used for the analyses. Results: The growth of scientific papers related to this topic can be divided into two stages: before and after 2006. Overall, the growth of the relevant literature was in line with Price’s literature growth curve. Subrata Ghosh and Antonio Gasbarrini are the authors with the highest academic influence in the field, and Lee D.’s research results are widely recognized by researchers in this field. Among the 72 countries involved in the study, the United States contributed the most, while China developed rapidly with regard to research being carried out in this area. From a regional perspective, countries and institutions in North America, Europe, and East Asia have made the most significant contributions to this field and have the closest cooperation. Among the 1074 articles included in the study, the most influential ones tended to consider the mechanism of the effect of dietary patterns on IBD from the perspective of the microbiome. Multiple tools were used for keyword analysis and mutual verification. The results showed that NF-κB, the Mediterranean diet, fatty acids, fecal microbiota, etc., are the focus and trends of current research. Conclusions: A Mediterranean-like dietary pattern may be a good dietary habit for IBD patients. Carbohydrates, fatty acids, and inulin-type fructans are closely related to IBD. Fatty acid, gut microbiota, NF-κB, oxidative stress, and endoplasmic reticulum stress are the hot topics in the study of the effects of dietary patterns on IBD and will be emerging research trends.

In this paper, the problems of system design, dynamic modeling, and trajectory tracking control of coaxial hybrid aerial underwater vehicles (HAUVs) with time-varying model parameters and composite marine environment disturbances are investigated. It is clear that a stable transition between different media remains a challenge in the practical implementation of amphibious tasks. For HAUVs, accurate dynamic modeling to describe complex dynamic variations during vehicle takeoff from underwater to air is a huge challenge. Meanwhile, due to the rapid changes in model parameters and the external environment, vehicles are likely to fall into the sea during the cross-domain process. An integrated continuous dynamic model considering hydrodynamic changes is established by introducing a linear switching coefficient during the process of trans-medium motion. A nonsingular fast terminal sliding-mode control (NFTSMC) algorithm combined with adaptive technology is used to design the position and attitude of the controller. With no previous knowledge of external interferences and lumped uncertainties of the HAUV, the adaptive NFTSMC (ANFTSMC) algorithm achieves the control objectives; at the same time, the inherent chattering problems of sliding mode control (SMC) are weakened. The finite-time stability of the global system is proven strictly using a series of mathematical derivations based on Lyapunov theory. The effect of the controller applied is analyzed through a series of simulations with representative working conditions. The results show that the proposed ANFTSMC can realize a “seamless” air–water trans-medium process, which proves the superiority and robustness of the proposed control algorithm.

Streptococcus agalactiae is a significant pathogen that can affect both human beings and animals. The extensive current use of antibiotics has resulted in antibiotic resistance. In our previous research, we found that zinc oxide quantum dots (ZnO QDs) had inhibitory effects on antibiotic-resistant microorganisms. In this study, a strain of Streptococcus agalactiaeWJYT1 with a broad antibiotic-resistant spectrum was isolated and identified from Lama glama at Sichuan Agricultural University Teaching Animal Hospital. The genome for the resistance and virulence genes was analyzed. Additionally, the antibacterial effects and anti-virulence mechanism of ZnO QDs for S. agalactiaeWJYT1 were investigated. The results showed that the genome of S. agalactiaeWJYT1 is 1,943,955 bp, containing 22 resistance genes and 95 virulence genes. ZnO QDs have a good antibacterial effect against S. agalactiaeWJYT1 by reducing bacterial growth and decreasing the expression of virulence genes, including bibA, hylB, sip, and cip, which provides a novel potential treatment for S. agalactiae.

Litchi leaf diseases and pests can lead to issues such as a decreased Litchi yield, reduced fruit quality, and decreased farmer income. In this study, we aimed to explore a real-time and accurate method for identifying Litchi leaf diseases and pests. We selected three different orchards for field investigation and identified five common Litchi leaf diseases and pests (Litchi leaf mite, Litchi sooty mold, Litchi anthracnose, Mayetiola sp., and Litchi algal spot) as our research objects. Finally, we proposed an improved fully convolutional one-stage object detection (FCOS) network for Litchi leaf disease and pest detection, called FCOS for Litch (FCOS-FL). The proposed method employs G-GhostNet-3.2 as the backbone network to achieve a model that is lightweight. The central moment pooling attention (CMPA) mechanism is introduced to enhance the features of Litchi leaf diseases and pests. In addition, the center sampling and center loss of the model are improved by utilizing the width and height information of the real target, which effectively improves the model’s generalization performance. We propose an improved localization loss function to enhance the localization accuracy of the model in object detection. According to the characteristics of Litchi small target diseases and pests, the network structure was redesigned to improve the detection effect of small targets. FCOS-FL has a detection accuracy of 91.3% (intersection over union (IoU) = 0.5) in the images of five types of Litchi leaf diseases and pests, a detection rate of 62.0/ms, and a model parameter size of 17.65 M. Among them, the detection accuracy of Mayetiola sp. and Litchi algal spot, which are difficult to detect, reached 93.2% and 92%, respectively. The FCOS-FL model can rapidly and accurately detect five common diseases and pests in Litchi leaf. The research outcome is suitable for deployment on embedded devices with limited resources such as mobile terminals, and can contribute to achieving real-time and precise identification of Litchi leaf diseases and pests, providing technical support for Litchi leaf diseases’ and pests’ prevention and control.

At present, there is little research on the impact of small hydropower stations on aquatic biodiversity. In order to investigate whether the existence of small hydropower stations has a significant impact on the aquatic biodiversity of their watersheds, we conducted a systematic study on the abundance of plankton, benthic animal, fish and microorganism in the watersheds of 15 small hydropower stations in Qionglai City. The results showed that 59 species of phytoplankton from 3 divisions, 16 species of zooplankton from 4 categories, 25 species of benthic animal from 3 phyla and 30 species of fish were found in the study basin. The analysis of the physical and chemical indicators of water bodies and the distribution characteristics of aquatic organisms found that the operation of small diversion-type power stations in Qionglai City changed part of the aquatic habitat in the basin, with a greater impact on the activities of large aquatic animals (fish) and a smaller impact on plankton and microorganism, and the intensity of the impact was shown as fish > benthic animal > plankton > microorganism. The small hydropower stations in this study have an impact but not significant on the aquatic biodiversity in the Baimo and Wenjing River in the Qionglai City, and this study provides a data reference for the comprehensive assessment of the environmental impact of small hydropower stations.

This paper studies the consensus tracking control for a class of uncertain high-order nonlinear multi-agent systems under an undirected leader-following architecture. A novel distributed finite-time adaptive control framework is proposed based on the barrier function. The distributed cascaded high-gain observers are introduced to solve the problem of robust consensus tracking with unmeasured intermediate states in multi-agent systems based on the proposed control framework. The proposed control schemes guarantee the finite-time consensus of multi-agent systems, which is proven by the finite-time Lyapunov stability and singular perturbation theory. In conclusion, numerical simulations verify the proposed control protocols’ effectiveness, and their performance advantages are shown by comparing them with another existing method.

To determine the origin of oscillatory potentials (OPs), binocular electroretinogram (ERG) recordings were performed under light and dark adaptation on adult healthy C57BL/6J mice. In the experimental group, 1 μL of PBS was injected into the left eye, while the right eye was injected with 1 μL of PBS containing different agents: APB, GABA, Bicuculline, TPMPA, Glutamate, DNQX, Glycine, Strychnine, or HEPES. The OP response depends on the type of photoreceptors involved, showing their maximum response amplitude in the ERG induced by mixed rod/cone stimulation. The oscillatory components of the OPs were affected by the injected agents, with some drugs inducing the complete abolition of oscillations (APB, GABA, Glutamate, or DNQX), whereas other drugs merely reduced the oscillatory amplitudes (Bicuculline, Glycine, Strychnine, or HEPES) or did not even affect the oscillations (TPMPA). Assuming that rod bipolar cells (RBC) express metabotropic Glutamate receptors, GABAA, GABAC, and Glycine receptors and that they release glutamate mainly on Glycinergic AII amacrine cells and GABAergic A17 amacrine cells, which are differently affected by the mentioned drugs, we propose that RBC-AII/A17 reciprocal synapses are responsible for the OP generation in the ERG recordings in the mice. We conclude that the reciprocal synapses between RBC and AII/A17 are the basis of the ERG OP oscillations of the light response, and this fact must be taken into consideration in any ERG test that shows a decrease in the OPs’ amplitude.

Background: To reduce the high incidence and mortality of gastric cancer (GC), we aimed to develop deep learning-based models to assist in predicting the diagnosis and overall survival (OS) of GC patients using pathological images. Methods: 2333 hematoxylin and eosin-stained pathological pictures of 1037 GC patients were collected from two cohorts to develop our algorithms, Renmin Hospital of Wuhan University (RHWU) and the Cancer Genome Atlas (TCGA). Additionally, we gained 175 digital pictures of 91 GC patients from National Human Genetic Resources Sharing Service Platform (NHGRP), served as the independent external validation set. Two models were developed using artificial intelligence (AI), one named GastroMIL for diagnosing GC, and the other named MIL-GC for predicting outcome of GC. Findings: The discriminatory power of GastroMIL achieved accuracy 0.920 in the external validation set, superior to that of the junior pathologist and comparable to that of expert pathologists. In the prognostic model, C-indices for survival prediction of internal and external validation sets were 0.671 and 0.657, respectively. Moreover, the risk score output by MIL-GC in the external validation set was proved to be a strong predictor of OS both in the univariate (HR = 2.414, P

Background: Recent studies have suggested that soluble suppression of tumorigenicity-2 (sST2), an inflammation-related protein receptor, is associated with atherosclerotic diseases. This study aimed to investigate the potential predictive value of sST2 on plaque vulnerability by assessing whether elevated serum levels of sST2 are associated with vulnerable plaque features in patients with non-ST-elevation acute coronary syndrome (ACS).Methods: A total of 120 patients with non-ST-elevation ACS (167 lesions) were prospectively enrolled and evaluated by standard coronary computed tomography angiography (CCTA) and coronary angiography in this study. Serum sST2 levels were measured by ELISA (Presage® ST2 Assay Kit, Critical Diagnostics), and semiautomated software (QAngioCT, Medis) was used to quantify coronary plaques.Results: The included patients were divided into 4 groups by serum sST2 level quartiles. Volumetric analysis of the whole lesion revealed that patients with higher sST2 levels had a larger absolute necrotic core (NC) volume (Quartile 4 vs. Quartile 1, 86.16 ± 59.71 vs. 45.10 ± 45.80 mm3, P = 0.001; Quartile 4 vs. Quartile 2, 86.16 ± 59.71 vs. 50.22 ± 42.56 mm3, P = 0.002) and a higher NC percentage (Quartile 4 vs. Quartile 1, 35.16 ± 9.82 vs. 23.21 ± 16.18%, P < 0.001; Quartile 4 vs. Quartile 2, 35.16 ± 9.82% vs. 22.50 ± 14.03%, P < 0.001; Quartile 4 vs. Quartile 3, 35.16 ± 9.82% vs. 25.04 ± 14.48%, P < 0.001). Correlation analysis revealed that serum sST2 levels were positively correlated with the NC (r = 0.323, P < 0.001) but negatively correlated with dense calcium (r = −0.208, P = 0.007). Furthermore, among those with plaque calcification, patients with spotty calcification exhibited higher serum sST2 levels than those with large calcification (26.06 ± 16.54 vs. 17.55 ± 7.65 ng/mL, P = 0.002). No significant differences in plaque components at the level of the minimal lumen area (MLA) were found among the groups.Conclusions: Serum sST2 levels were correlated with different coronary plaque components in patients with non-ST-elevation ACS. A higher serum level of sST2 was correlated with plaque vulnerability.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT04797819.

The immersed boundary method has been widely used for simulating flows over complex geometries. However, its accuracy in predicting the statistics of near-wall turbulence has not been fully tested. In this work, we evaluate the capability of the curvilinear immersed boundary (CURVIB) method in predicting near-wall velocity and pressure fluctuations in turbulent channel flows. Simulation results show that quantities including the time-averaged streamwise velocity, the rms (root-mean-square) of velocity fluctuations, the rms of vorticity fluctuations, the shear stresses, and the correlation coefficients of u′ and v′ computed from the CURVIB simulations are in good agreement with those from the body-fitted simulations. More importantly, it is found that the time-averaged pressure, the rms and wavenumber-frequency spectra of pressure fluctuations computed using the CURVIB method agree well with the body-fitted results.

Plant-based natural products represent an alternative to chemical compounds for the control of mites in veterinary medicine. Here, the essential oil of Elsholtzia densa (E. densa) Benth was extracted using hydrodistillation at a rate of 1.2%. The chemical composition of the essential oil was determined by gas chromatography-mass spectrometry (GC-MS) analysis. The GC-MS analysis indicated that the principal compounds in the volatile oil of the sample were 4-Pyridinol (28.16%) and thymol (26.58%). The acaricidal activity of E. densa oil against Sarcoptes scabiei (S. scabiei) was tested in vitro. Toxicity test data were analysed using a complementary log-log (CLL) model. The E. densa oil was prepared in five concentrations by dilution with liquid paraffin (1, 2, 4, 8 and 16 mg/ml) and exhibited strong toxicity against S. scabiei with LT50 values of 16.637, 5.075, 2.884, 1.184 and 0.760 h, respectively. The LC50 values were 7.678, 4.623, 2.543, 1.502, 1.298 and 0.981 mg/ml for S. scabiei at 1, 2, 4, 8, 16 and 24 h, respectively. Compared to the control, the essential oil showed significant effects against S. scabiei in vitro. At 16 mg/ml, E. densa oil was found to kill all mites within a 16-h period. The results indicate that E. densa oil possesses potential acaricidal activity in vitro and may be exploited as a novel drug for the effective control of S. scabiei.

Data in this article are associated with the research article “Ampholytic ion-exchange materials coated with small zwitterion for high-efficacy purification of ionizable soluble biomacromolecules” (Rao et al., 2018) [1]. This article provided data on how to design ampholytic ion-exchange material (AIEM) for the purification of ionizable soluble biomacromolecules for both high activity yields and favorable homogeneity, with two uricases as protein models and a plasmid as DNA model. Data were made publicly available for further analyses.

Through genome-wide association studies (GWAS), multiple inherited predispositions to acute lymphoblastic leukemia (ALL) have been identified in children. Most recently, a novel susceptibility locus at ERG was localized, exhibiting Hispanic-specific manner. In this study, we conducted a replication study to in all-age Chinese patients (N = 451), not only validating the novel ERG locus, but also systematically determining the impact of age on association status of the top GWAS signals. We found that single nucleotide polymorphisms at ARID5B, IKZF1, CEBPE, PIP4K2A were only significantly associated with ALL susceptibility in childhood patients with no BCR-ABL fusion, while GATA3 signal exhibited its significance in adults no matter carrying BCR-ABL fusion or not. Moreover, the novel ERG SNP can be validated in pediatric patients without both BCR-ABL and ETV6-RUNX1 fusion. Our finding suggests the modifying effects of age on genetic predisposition to ALL, and highlights the impact of ERG SNP in Chinese patients.

A small proportion of patients with acute lymphoblastic leukemia (ALL) may experience severe leukopenia after treating with 6-mercaptopurine (6MP), which can be largely explained by germline variants in TPMT and NUDT15. However, a minority of patients who suffered such adverse drug reaction have NUDT15wt/wtTPMTwt/wt genotype, indicating that other genetic factors may take part in. In this study, we genotyped 539 exon-located nonsilent pharmacogenetic variants in genes involved in phase I/II of drug metabolism in 173 pediatric patients with ALL and conducted association screening for 6MP-induced leukopenia. Besides NUDT15 (rs116855232, P = 6.4 × 10−11) and TPMT (rs1142345, P = 0.003), a novel variant was identified in CYP2A7 gene (i.e., rs73032311, P = 0.0007), which is independent of NUDT15/TPMT variant. In addition, a variant (i.e., rs4680) in COMT is significantly associated with 6MP-induced hepatotoxicity (P = 0.007). In conclusion, variants in CYP2A7 and COMT may be considered as novel potential pharmacogenetic markers for 6MP-induced toxicities, but additional independent validations with large sample size and investigations on related mechanisms are further needed.

Signet-ring cell carcinoma (SRCC) is a unique type of gastric cancer with no prognostic features. Here, the authors report a CLDN18-ARHGAP26/6 gene fusion in patients with a high signet-ring cell content, poor survival outcomes, and who experience no benefit from platinum/fluoropyrimidines-based chemotherapy.

Data in this article are associated with the research article “Highthroughput estimation of specific activities of enzyme/mutants in cell lysates through immunoturbidimetric assay of proteins” (Yang et al., 2017) [1]. This article provided data on how to develop an immunoturbidimetric assay (ITA) of enzyme/mutants as proteins in cell lysates in high-throughput (HTP) mode together with HTP assay of their activities to derive their specific activities in cell lysates for comparison, with Pseudomonas aeruginosa arylsulfatase (PAAS) and Bacillus fastidious uricase (BFU) plus their mutants as models. Data were made publicly available for further analyses.

Some discrepancies have been observed in the diagnostic efficacy of multifocal visual evoked potential (mfVEP) when evaluating visual field defects in glaucoma patients. Therefore, we evaluated the diagnostic precision of the mfVEP in glaucoma to find its best diagnostic indicator. A systematic review and meta-analysis of quantitative studies published up to 1 April 2021 was performed. The methodological quality of the included articles was assessed. Publication bias analysis and heterogeneity tests were performed. The sensitivity, specificity and diagnostic odds ratio were calculated. The area under the curve (AUC) was calculated using the summary of receiver operating characteristics curve. Six studies with a total of 241 patients were included according to the inclusion and exclusion criteria. The AUC was 0.98. There was no evidence of publication bias or threshold effect. The pooled sensitivity and pooled specificity of the mfVEP amplitude for detection of visual field defects in all studies was 0.93 and 0.89, respectively. The positive and negative likelihood ratios of mfVEP amplitude were 6.56 and 0.08, respectively. The amplitude of mfVEP showed a good diagnostic precision in the prediction of visual field defects. Interocular mfVEP amplitude analysis can be a good diagnostic indicator for visual field study.

Between the cornea and the posterior pole of the eye, there is a transepithelial potential capable of being registered through an electrooculogram (EOG). It is questionable whether electrooculographic responses are similar in both eyes despite ocular dominance in human beings. We studied the effect of different electrooculographic stimulation parameters, in terms of directionality, linear and angular velocity, contrast, and state of adaptation to light/dark, that may induce possible interocular differences in visual function. The study was carried out with electroencephalography-type surface electrodes placed in the medial, lateral, superior, and inferior positions of both human eyes to record the eye movements. We found a greater amplitude of the EOG response in the left eye than to the right eye for light bars moving from right to left (p < 0.01; t-test). The EOG response amplitude was similar in both eyes for light bars moving in vertical directions, but greater than horizontal or rotational stimuli. We conclude that vertical stimuli should be used for EOG functional evaluation of eye movements, since horizontal stimuli generate significant interocular differences.

Eleven tropical cyclones that landed in Guangdong Province since 2012 and experienced strengthening or weakening over the offshore area were studied. Since the structure of the tropical cyclone boundary layer significantly influences the variation of the intensity of the cyclone, continuous observations of the wind profile radar at a coastal radar station in Guangdong Province were combined with aircraft observation data of the No. 1604 “Nida” cyclone to analyse the variations in the distributions of the radial wind, tangential wind, and angular momentum in the typhoon boundary layer and the similarities and differences between the boundary layers of the 11 tropical cyclones during the strengthening or weakening of their intensities. The analysis results show that the presence of the supergradient wind and the enhancement effect of the radial inflow play important roles in enhancing the intensity of a tropical cyclone. The observations indicate that when the tangential wind velocity in the maximum wind velocity radius reaches the velocity of the supergradient wind and when the radial inflow either gradually increases towards the centre of the tropical cyclone or gradually covers the entire boundary layer, the angular momentum tends to be shifted towards the centre. At this time, the maximum radial inflow, maximum tangential wind, and maximum angular momentum are in the same height range in the vertical direction. When a strong radial outflow occurs in the boundary layer of a tropical cyclone or the area with maximum wind velocity is located in the air outflow, the angular momentum cannot easily be transported towards the centre of the typhoon. Therefore, the spatial configuration of the three physical quantities will determine future changes in the intensity of tropical cyclones. The scope of the results presented here is limited to the 11 selected cases and suggests extending the analysis to more data.

Germline variants of PIP4K2A impact susceptibility of acute lymphoblastic leukemia (ALL) through inducing its overexpression. Although limited reports suggested the oncogenic role of PIP4K2A in cancers, regulatory network and prognostic effect of this gene remains poorly understood in tumorigenesis and leukemogenesis. In this study, we conducted genome-wide gene expression association analyses in pediatric B-ALL cohorts to discover expression associated genes and pathways, which is followed by the bioinformatics analyses to investigate the prognostic role of PIP4K2A and its related genes in multiple cancer types. 214 candidates were identified to be significantly associated with PIP4K2A expression in ALL patients, with known cancer-related genes rankings the top (e.g., RAC2, RBL2, and TFDP1). These candidates do not only tend to be clustered in the same types of leukemia, but can also separate the patients into novel molecular subtypes. PIP4K2A is noticed to be frequently overexpressed in multiple other types of leukemia and solid cancers from cancer cohorts including TCGA, and associated with its candidates in subtype-specific and cancer-specific manners. Interestingly, the association status varied in tumors compared to their matched normal tissues. Moreover, PIP4K2A and its related candidates exhibit stage-independent prognostic effects in multiple cancers, mostly with its lower expression significantly associated with longer overall survival (p < 0.05). Our findings reveal the transcriptional regulatory network of PIP4K2A in leukemia, and suggest its potentially important role on molecular subtypes of multiple cancers and subsequent treatment outcomes.

A rare severe case of the coinfection of cerebral falciparum malaria and dengue is reported in this paper. The patient was a 50 yr old male in the north of China, who returned from Uganda not long ago and suffered unconsciousness after fever for 4 d before the falciparum malaria and dengue infection was diagnosed via blood smear microscopy, RT-PCR and serology, although the antimalarial and symptomatic treatment was carried out, ultimately the patients died of septic shock because of multiple organ dysfunctions. This case report showed such a coinfection was prone to cause severe acute consequence. The timely diagnosis and delicate treatment are crucial for prognosis of patients

Like DIP-STR markers (deletion/insertion polymorphism-short tandem repeat combinations), SNP-STR markers (single nucleotide polymorphism-STR combinations) are also valuable in forensic DNA mixture analysis. In this study, eight SNP-STRs were selected, and a stable and sensitive multiplex polymerase chain reaction (PCR) assay was developed for amplifying these SNP-STRs and the Amelogenin gender marker according to the principle of amplification refractory mutation system (ARMS). This novel multiplex set allows detection of the minor DNA contributor in a DNA mixture of any gender and cellular origin with high resolution (beyond a DNA ratio of 1:20). In addition, SNP-STR haplotype frequencies were estimated based on a survey of 350 unrelated individuals from Chinese Han population, and the combined power of discrimination (PD) and power of exclusion (PE) of the eight SNP-STRs were calculated as 0.99999999965 and 0.9996, which were obviously higher than that of the eight STR loci: 0.9999999954 and 0.9989 respectively. The results indicated that the SNP-STR compound markers have higher application value in forensic identification compared to standard autosomal STRs, especially in the analysis of imbalanced DNA mixtures.

Abstract Adherens junctions-associated protein 1 (AJAP1) is an integral membrane protein that is thought to function as a tumor suppressor in various malignancies. Downregulation of AJAP1 mRNA levels may predict recurrence in hepatocellular carcinoma (HCC) patients, but the underlying molecular mechanism is unknown. This was addressed in the present study by examining the role of AJAP1 in HCC cell proliferation, migration, and invasion in vitro as well as in human specimens and mouse xenograft model. We found that AJAP1 expression was reduced in HCC cells and human HCC tissue, which was associated with metastasis. AJAP1 overexpression inhibited HCC progression and metastasis, while its silencing had the opposite effect both in vitro and in vivo. Furthermore, AJAP1 blocked epithelial–to–mesenchymal transition by interacting with β-catenin and inhibiting its nuclear translocation, which suppressed zinc finger E-box binding homeobox 1 (ZEB1) transcription. These results indicate that AJAP1 inhibits HCC metastasis, and is thus a potential therapeutic target for HCC treatment.

Military named entity recognition (MNER) is one of the key technologies in military information extraction. Traditional methods for the MNER task rely on cumbersome feature engineering and specialized domain knowledge. In order to solve this problem, we propose a method employing a bidirectional long short-term memory (BiLSTM) neural network with a self-attention mechanism to identify the military entities automatically. We obtain distributed vector representations of the military corpus by unsupervised learning and the BiLSTM model combined with the self-attention mechanism is adopted to capture contextual information fully carried by the character vector sequence. The experimental results show that the self-attention mechanism can improve effectively the performance of MNER task. The F-score of the military documents and network military texts identification was 90.15% and 89.34%, respectively, which was better than other models.

The silico-ferrite of calcium and aluminum (SFCA) is a significant crystalline phase that bonds in high basicity sinter. Al2O3 and SiO2 play an important role in the formation of SFCA in the Fe2O3⁻CaO⁻SiO2⁻Al2O3 system, but the effect mechanism of Al2O3 and SiO2 on the formation of SFCA is unclear. To investigate this effect, sintering experiments were carried out with different temperatures and different times. It was found that the reaction of Al2O3 with CaFe2O4 (CF) as an initial product was easier to form during the calcium iron aluminum oxide (CFA) than that of SiO2 with CF to form SFC. This was due to the former directly forming to CFA while the latter initially formed Ca2SiO4 (C2S) and Ca2.5Fe15.5O25, and then SFC. It was also observed that when Al2O3 and SiO2 existed simultaneously, the Al2O3 initially reacted with CF to form CFA at 1100 °C, while the SiO2 participated in the formation of SFCA at 1150 °C without the formation of SFC. Moreover, it was understood that these were different effects in that the Al2O3 promoted the transformation from the orthorhombic crystal system to the triclinic crystal system, while the SiO2 dissolved into CFA to form the SFCA phase when Al2O3 existed.

For enzymatic analysis to quantify a substrate or enzyme, kinetic analysis of reaction curve can be integrated with a proper classical approach. For their integration, they should have consistent slopes and intercepts of linear response and an overlapped region of analyte quantities measurable under optimized conditions. To quantify a substrate after optimizations of tool enzyme activity and reaction duration, the equilibrium method works when the reaction is completed within the reaction duration; otherwise, kinetic analysis of reaction curve applies providing at least seven data with sufficient consumption of substrate. To quantify an enzyme after optimizations of initial substrate concentration and reaction duration, the classical initial rate method works when an estimated initial rate locates within the linear range; otherwise, kinetic analysis of reaction curve applies after the conversion of the quantification index with optimized parameters. This integration strategy has ideal linear ranges and practical efficiency for quantifying an enzyme at moderate substrate levels and for quantifying a substrate at moderate cost on tool enzyme; it has promise to simultaneous assays of multiple enzymes in one reaction vessel each time and ,thus, potential applications to concurrently quantify multiple serum enzymes, screen inhibitors against multiple enzyme targets, and detect multiple serum components by enzymeimmunoassay.