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Abstract Background Zhushao Granules (ZSG) had exhibited beneficial effects in the treatment of ulcerative colitis (UC) as an effective herbal prescription in Traditional Chinese Medicine. However, the underlying anti-inflammatory mechanism of ZSG remains unclear. This study aimed to decipher the mechanism of ZSG against UC combining network pharmacology and animal-based experiments. Methods Network pharmacology was employed to identify active components and therapeutic targets of ZSG against UC. The protein–protein interaction (PPI) network was constructed among the therapeutic targets using the STRING database, and GO and pathway analyses were carried out using DAVID. Then, the “herb-component-target-pathway” network based on therapeutic targets was established and the topological parameters were subsequently calculated to identify hub active components, targets and pathways by Cytoscape. Finally, the therapeutic function and the special pathway of ZSG against UC were validated using a TNBS-induced UC model in BABL/c mice. Results Ninety-four active components of ZSG and 460 potential targets were acquired from the Encyclopedia of Traditional Chinese Medicine and Tradition Chinese Medicine Systems Pharmacology Database and Analysis Platform. 884 potential targets of UC were obtained from OMIM and HINT. Sixty-two overlapping potential targets were identified as therapeutic targets of ZSG against UC. PPI network filtered out 61 therapeutic targets. GO and pathway analyses extracted 48, 25, and 98 terms corresponding to biological processes, molecular functions and Reactome pathways, respectively. Enrichment analysis suggested that the therapeutic targets were mainly involved in immune regulation, especially RIP-mediated NF-κB activation via ZBP1. Topological analysis of the “herb-component-target-pathway” network recognized 9 hub components, 20 hub targets and 18 hub pathways. The animal-based experiments revealed that ZSG ameliorated symptoms and histological changes in TNBS-induced colitis by significantly inhibiting the ZBP1/RIP/NF-κB pathway. Conclusions ZSG might alleviate the mucosal damage and ameliorate colitis via targeting ZBP1/RIP/NF-κB pathway, which laid the theoretical foundation for the clinical application and further study of ZSG and provided new insights into UC treatment.

The Lower Silurian Longmaxi Formation is a major horizon for shale gas development in the Changning block in Sichuan Basin. In this study, the fracture features in the Longmaxi Formation in the Changning block were investigated through outcrop observation, core description, inclusion testing, and Fullbore Formation MicroImage logging. The results showed that tectogenetic shear fractures dominated the Longmaxi Formation, with maximum principal stress in the SSW, NW, and NE directions. According to fracture features and stress analysis, three phases of faults were generated by tectonic movements after the buried depth reached a maximum in the study area: phase 1 nearly EW-trending faults formed in the middle-late Yanshanian, phase 2 NE-trending faults formed from the end of the Yanshanian to the early Himalayan, and phase 3 NW-trending faults formed from the middle Himalayan to the present. According to the regression analysis of the tested shale gas production and faults, the faults with a throw of > 200 m could have a great effect on gas production, and high-yield wells were generally located over 1 km away from faults. Based on the dissection of tectonic styles and typical wells drilled in the Changning block, three shale gas accumulation models were established: wide gentle syncline + internal smalxl fault, subdued anticline + large fault, and slope + internal fault. The study reveals the mechanism of fault influence on shale gas accumulation in the Longmaxi Formation in the Changning block and provides a reference for efficient shale gas production in the Sichuan Basin.

BackgroundCardiovascular disease (CVD) is a major global health issue, with approximately 70% of cases linked to modifiable risk factors. Digital health solutions offer potential for CVD prevention; yet, their effectiveness in covering the full range of prevention strategies is uncertain. ObjectiveThis study aimed to synthesize current literature on digital solutions for CVD prevention, identify the key components of effective digital interventions, and highlight critical research gaps to inform the development of sustainable strategies for CVD prevention. MethodsFollowing PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we conducted a comprehensive search in Web of Science, Scopus, and PubMed to identify original English-language studies published between January 2000 and May 2024 that examined primary or secondary CVD prevention through digital solutions. The exclusion criteria included: telephone-only interventions, abstract-only publications, methodology-focused studies without primary data, studies without participants or specific groups, and studies with no follow-up period. The literature search used the string with terms like “digital health,” “mHealth,” “mobile health,” “text message,” “short message service,” “SMS,” “prevention,” “prevent,” “cardiovascular disease,” “CVD,” etc. Study bias was assessed using the RoB 2 (Cochrane Collaboration) and the ROBINS-I tool (Cochrane Collaboration). Data on prevention components, prevention types, study design, population, intervention, follow-up duration, personnel, and delivery settings were extracted. ResultsA total of 2871 studies were identified through the search. After excluding ineligible studies, 30 studies remained, including 24 randomized controlled trials. The reviewed digital solutions for CVD prevention focused on baseline assessment (29/30, 97%), physical activity counseling (18/30, 60%), tobacco cessation (14/30, 47%), blood pressure management (13/30, 43%), and medication adherence (10/30, 33%). The technologies used were categorized into 3 types, smartphones and wearables (16/30, 53%), email and SMS communications (12/30, 40%), and websites or web portals (3/30, 10%). The majority of the study outcomes addressed blood pressure (14/30, 47%), exercise capacity (12/30, 40%), weight (12/30, 40%), and lipid profile (11/30, 37%), while fewer focused on nicotine dependence (9/30, 30%), medication use (8/30, 27%), quality of life (7/30, 23%), dietary habits (5/30, 17%), intervention adherence (4/30, 13%), waist circumference (4/30, 13%), and blood glucose levels (2/30, 7%). ConclusionsDigital solutions can address challenges in traditional CVD prevention by improving preventive behaviors and monitoring health indicators. However, most evaluated interventions have focused on medication use, quality of life, dietary habits, adherence, and waist circumference. Further studies are needed to assess the long-term impact of more comprehensive interventions on key cardiovascular outcomes.

Oncolytic viruses have emerged as a highly promising modality for cancer treatment due to their ability to replicate specifically within tumors, carry therapeutic genes, and modulate the immunosuppressive tumor microenvironment through various mechanisms. Additionally, they show potential synergy with immune checkpoint inhibitors. A study report indicates that from 2000 to 2020, 49.5% of oncolytic viruses were administered intratumorally and 35% intravenously during clinical trials. However, both administration methods face significant challenges, particularly with intravenous delivery, which encounters issues such as non-specific tissue uptake, neutralizing antibody responses, and antiviral effects mediated by various immune cells. Despite extensive research into the antiviral roles of CD8+ T cells and NK cells in oncolytic virus therapy, neutrophils—constituting approximately 50% to 70% of human peripheral blood leukocytes—have received relatively little attention. Neutrophils are the most abundant leukocyte subset in peripheral circulation, known for their phagocytic activity. Beyond their traditional roles in bacterial and fungal infections, emerging literature suggests that neutrophils also play a critical role in the body’s antiviral responses. Given the gaps in understanding the role of neutrophils in oncolytic virus therapy, this article reviews current literature on this topic. It aims to provide a theoretical foundation for developing oncolytic virus-based cancer therapies and enhancing their anti-tumor efficacy in future clinical treatments.

In recent years, significant progress has been made in China in the field of deep-sea large yellow croaker (Larimichthys crocea) farming. Compared with the traditional inshore aquaculture model, deep-sea culture of large yellow croaker enjoys a wider growing space with better water quality, thus enhancing fish quality. However, deep-sea aquaculture also faces challenges such as typhoons and strong currents, which often lead to prolonged starvation in fish. Therefore, in order to further promote the technological advancement of large yellow croaker in the field of deep-sea aquaculture, this experiment aimed to investigate the effects of varying starvation durations on the feeding rhythm and physiological state of large yellow croaker. With an initial body mass of 122.62 ± 11.08 g and a body length of (17.9 ± 1.04) cm as the samples, the experiment was divided into five groups, which were starved for 0 d (S0), 2 d (S2), 4 d (S4), 8 d (S8), and 16 d (S16) before resumption of feeding. The results were as follows: under starvation stress for 8 consecutive days, the total duration of feeding gradually decreased in large yellow croaker, but increased at starvation up to 16 days. Each replicate group had 50 large yellow croakers as test subjects, for a total of 750 large yellow croakers. Analyzing the linear regression equations of S0 with S2, S4, S8, and S16 groups, it was found that the trend of rate of change in feeding duration was consistent with the total duration of feeding, i.e., it decreased during 8 days and increased at 16 days. It indicated that the rate of feeding of large yellow croaker was accelerated within 8 days of starvation, while the rate of feeding was slowed down at 16 days of starvation. Furthermore, the blood glucose concentration of large yellow croaker decreased significantly after 8 days of starvation, while it rebounded significantly in the S16 group. Meanwhile, large areas of fatty degeneration were observed in the liver on the 8th day of starvation, followed by extensive hepatocyte necrosis on the 16th day. After resumption of feeding, there was some recovery within 4 days, but hepatocytes were still extensively edematous in the S8 and S16 groups. Meanwhile, the expression of inflammatory factor genes such as IL-1β, IL-10 and TNF-α in the liver increased with the prolongation of starvation time, in which both S8 and S16 groups in the liver were significantly different from the S0 group, and after resumption of feeding, the IL-1β and TNF-α genes of the S8 and S16 groups were significantly different from those of the normal feeding group (p < 0.05), while there was no differentiation for the IL-10 gene. Therefore, based on the results of this study, it is recommended to limit the duration of starvation in the large yellow croaker to no more than 8 days.

Phytoremediation is a sustainable way to clean contaminated urban soil, but selecting the right plants and designing communities is crucial. This study focuses on the vegetation in a disused steel plant in Chongqing, China, abandoned for nearly two decades. The goal is to reveal the plant community and succession patterns to inform the restoration of brownfield sites. This study combined the sample line and plot to investigate the vegetation and its growth environment in the Steel Plant. Information was recorded, including plant species, quantity, distribution, soil nutrients, humidity, and light. Cluster analysis categorized plant community types, and redundancy analysis examined the link between environmental conditions and plant types. The study found that: 1) There are 65 plant species (including 13 native trees) in the steel plant’s brownfield area, with Broussonetia papyrifera, Pteris vittata, and Debregeasia orientalis being the most abundant. The plants inside the plant were divided into seven groups based on species composition. 2) Soil moisture showed a significant positive correlation (Pearson index of 0.628) with plant survival, followed by a notable correlation with light intensity. 3) Environmental conditions partly influenced plant species composition and abundance variations. 4) 11 hyper-accumulating plant species were identified, focusing on three: the As hyper-accumulator Pteris vittata and the Cd hyper-accumulators Solanum nigrum and Debregeasia orientalis. The findings of this research will offer valuable insights for applying phytoremediation techniques in addressing contamination issues in brownfields within steel plants.

Key Clinical Message Traumatic posterior atlantoaxial dislocation combined with Jefferson fracture and odontoid process fracture with vertebral artery injury is rare. The management of such injury raises controversial issues and is still open to debate. A 74‐year‐old Chinese male presented with sustained neck pain and stiffness after falling from height. The patient was neurologically intact. Preoperative radiographs demonstrated a Jefferson burst fracture with a posterior dislocation of the atlantoaxial joints and odontoid process Anderson and D'alonzo type II fracture. A computed tomography angiography (CTA) showed an occluded left vertebral artery. Coil embolization in the proximal portion of the occluded vertebral artery was performed to prevent further cerebral infarction due to distal embolization of the thrombus. Then a second stage occipito‐cervical fusion was performed to reconstruct cervical spine stability. A systematic screening of blunt trauma vertebral artery injuries through CTA is required when dealing with upper cervical fracture. For cases with vertebral artery occlusion secondary to cervical spine injury, endovascular treatment preceding cervical spine surgery is a feasible and a safe treatment.

Flow velocity is a key environmental factor that affects the behavioral strategies and physiological homeostasis of fish. To study the effects of flow velocity on the behavioral changes and blood physiology of the yellow croaker, the behavioral patterns of yellow croakers in response to flow velocity stress were obtained by analyzing changes in tail wagging frequency and amplitude. Differences in blood glucose, lactate, and cortisol were compared to determine their appropriate flow rate ranges. The juvenile stage of the large yellow croaker is crucial, as environmental changes can affect the physiology of fish. Therefore, juvenile yellow croakers were selected as the experimental subjects for this study. Twenty-four healthy and uniformly sized large yellow croakers with body weights of (90.26 ± 9.91) g and body lengths of (19.91 ± 0.69) cm were randomly assigned to one control group and three experimental groups, with five fish in each group. The experimental group was set with three flow rates, namely 1 bl/s (20 cm/s), 2 bl/s (40 cm/s), and 3 bl/s (60 cm/s), with a flow rate stress duration of 1 h. The results showed that: (1) Under different flow velocities, the fish exhibited different tail wagging patterns. At low flow velocities, their tail fins exhibited a “C”-shaped swing, while at high flow velocities, their bodies exhibited an “S”-shaped swing. (2) Oscillation frequency and amplitude both increased with increasing flow velocity. At a flow velocity of 2 bl/s, the oscillation frequency significantly increased. When the flow velocity reached 3 bl/s, the oscillation amplitude significantly increased (p < 0.05). (3) Blood physiology showed significant changes with increased flow rate, and blood glucose content continuously decreased with increased flow rate, significantly decreasing at a flow rate of 2 bl/s (p < 0.05). Lactic acid and cortisol both increased with increasing flow rate, and significantly increased at a flow rate of 3 bl/s (p < 0.05). In summary, under high-flow velocity stress, significant changes occurred in the behavior and physiology of large yellow croakers, which were consistent with physiological changes in the blood. A flow rate higher than 2 bl/s can lead to intense swimming behavior, decreased blood sugar concentration, and increased lactate accumulation and stress levels. Therefore, the short-term tolerance of yellow croakers is 2 bl/s, and a flow rate of 1 bl/s is more suitable.

Background The only clinically approved drug that reduces doxorubicin cardiotoxicity is dexrazoxane, but its application is limited due to the risk of secondary malignancies. So, exploring alternative effective molecules to attenuate its cardiotoxicity is crucial. Colchicine is a safe and well‐tolerated drug that helps reduce the production of reactive oxygen species. High doses of colchicine have been reported to block the fusion of autophagosomes and lysosomes in cancer cells. However, the impact of colchicine on the autophagy activity within cardiomyocytes remains inadequately elucidated. Recent studies have highlighted the beneficial effects of colchicine on patients with pericarditis, postprocedural atrial fibrillation, and coronary artery disease. It remains ambiguous how colchicine regulates autophagic flux in doxorubicin‐induced heart failure. Methods and Results Doxorubicin was administered to establish models of heart failure both in vivo and in vitro. Prior studies have reported that doxorubicin impeded the breakdown of autophagic vacuoles, resulting in damaged mitochondria and the accumulation of reactive oxygen species. Following the administration of a low dose of colchicine (0.1 mg/kg, daily), significant improvements were observed in heart function (left ventricular ejection fraction: doxorubicin group versus treatment group=43.75%±3.614% versus 57.07%±2.968%, P=0.0373). In terms of mechanism, a low dose of colchicine facilitated the degradation of autolysosomes, thereby mitigating doxorubicin‐induced cardiotoxicity. Conclusions Our research has shown that a low dose of colchicine is pivotal in restoring the autophagy activity, thereby attenuating the cardiotoxicity induced by doxorubicin. Consequently, colchicine emerges as a promising therapeutic candidate to improve doxorubicin cardiotoxicity.

Abstract Approximately 20% of aged captive giant pandas (Ailuropoda melanoleuca) have cataracts that impair their quality of life. To identify potential biomarkers of cataract formation, we carried out a quantitative proteomics analysis of 10 giant pandas to find proteins differing in abundance between healthy and cataract-bearing animals. We identified almost 150 proteins exceeding our threshold for differential abundance, most of which were associated with GO categories related to extracellular localization. The most significant differential abundance was associated with components of the proteasome and other proteins with a role in proteolysis or its regulation, most of which were depleted in pandas with cataracts. Other modulated proteins included components of the extracellular matrix or cytoskeleton, as well as associated signaling proteins and regulators, but we did not find any differentially expressed transcription factors. These results indicate that the formation of cataracts involves a complex post-transcriptional network of signaling inside and outside lens cells to drive stress responses as a means to address the accumulation of protein aggregates triggered by oxidative damage. The modulated proteins also indicate that it should be possible to predict the onset of cataracts in captive pandas by taking blood samples and testing them for the presence or absence of specific protein markers.

At present, the potato’s mechanized harvesting rate in hilly and mountainous areas is very low. The reasons for this are that in heavy soil, the separation of potato rhizomes from soil or vines is not sufficient, harvesting machinery is seriously damaged by the potato epidermis, and the harvested potato is easily buried in soil, resulting in a missed harvest. In this paper, a two-stage cleaning potato harvester with wave-type and roller-group-type separating mechanisms was designed, and its overall structure and working principle are introduced in detail. The new cleaning mechanism can increase the effective separating length and effective contact area of the potato–soil mixture so as to achieve the purpose of removing clay and heavy soil. The main separator uses a structure that combines offset waves with opposite waves and a staggered arrangement of large–small diameter straight bars. The secondary separator adopts a device combining left-hand and right-hand separating rollers. The discrete element model of the whole machine was established, and the results of the theoretical analysis were verified by simulation. The key factors affecting the harvest quality were analyzed by variance analysis and response surface analysis, and the field experiment was carried out with the rate of clean potatoes, damaged potatoes, and peeled potatoes harvested as the indexes. The field experiments showed that the machine achieved a rate of photos on or out of the earth of 98.87%, a damaged potato rate of 0.91%, and a peeled potato rate of 1.13%. The research results provide theoretical support and a technical reference for the design and optimization of potato harvesters, as well as the improvement of the potato–soil separating efficiency and harvest quality.

Simultaneous Localization and Mapping (SLAM) is one of the key technologies with which to address the autonomous navigation of mobile robots, utilizing environmental features to determine a robot’s position and create a map of its surroundings. Currently, visual SLAM algorithms typically yield precise and dependable outcomes in static environments, and many algorithms opt to filter out the feature points in dynamic regions. However, when there is an increase in the number of dynamic objects within the camera’s view, this approach might result in decreased accuracy or tracking failures. Therefore, this study proposes a solution called YPL-SLAM based on ORB-SLAM2. The solution adds a target recognition and region segmentation module to determine the dynamic region, potential dynamic region, and static region; determines the state of the potential dynamic region using the RANSAC method with polar geometric constraints; and removes the dynamic feature points. It then extracts the line features of the non-dynamic region and finally performs the point–line fusion optimization process using a weighted fusion strategy, considering the image dynamic score and the number of successful feature point–line matches, thus ensuring the system’s robustness and accuracy. A large number of experiments have been conducted using the publicly available TUM dataset to compare YPL-SLAM with globally leading SLAM algorithms. The results demonstrate that the new algorithm surpasses ORB-SLAM2 in terms of accuracy (with a maximum improvement of 96.1%) while also exhibiting a significantly enhanced operating speed compared to Dyna-SLAM.

This paper aims to assess the effects of various laser cutting parameters on the surface roughness of 2 mm thick titanium–zirconium amorphous alloy sheets. With multiple linear regression, a mathematical model was proposed to predict the maximum height of surface Sz as a function of two laser cutting parameters: cutting speed and assist gas pressure. The adequacy of the proposed model was evaluated using the analysis of variance method. Scanning electron microscopy was then used to observe the surface topography of the material following laser cutting under different conditions. It was found that for a fixed laser power, cutting speed dominates the parameter that determines the maximum height of surface roughness.

Abstract Blood vessels play a role in osteogenesis and osteoporosis; however, the role of vascular metabolism in these processes remains unclear. The present study finds that ovariectomized mice exhibit reduced blood vessel density in the bone and reduced expression of the endothelial glycolytic regulator pyruvate kinase M2 (PKM2). Endothelial cell (EC)‐specific deletion of Pkm2 impairs osteogenesis and worsens osteoporosis in mice. This is attributed to the impaired ability of bone mesenchymal stem cells (BMSCs) to differentiate into osteoblasts. Mechanistically, EC‐specific deletion of Pkm2 reduces serum lactate levels secreted by ECs, which affect histone lactylation in BMSCs. Using joint CUT&Tag and RNA sequencing analyses, collagen type I alpha 2 chain (COL1A2), cartilage oligomeric matrix protein (COMP), ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), and transcription factor 7 like 2 (TCF7L2) as osteogenic genes regulated by histone H3K18la lactylation are identified. PKM2 overexpression in ECs, lactate addition, and exercise restore the phenotype of endothelial PKM2‐deficient mice. Furthermore, serum metabolomics indicate that patients with osteoporosis have relatively low lactate levels. Additionally, histone lactylation and related osteogenic genes of BMSCs are downregulated in patients with osteoporosis. In conclusion, glycolysis in ECs fuels BMSC differentiation into osteoblasts through histone lactylation, and exercise partially ameliorates osteoporosis by increasing serum lactate levels.

To address the problems of low bright rates and high rates of potato injuries, a left and right-hand rotation combination of potato–soil separation devices was developed. Its overall structure and working principle were introduced. A Texture Analyzer and pressure sensor were used to measure the force threshold of different varieties of potatoes. A discrete element model of separation rollers and potatoes was established. The collision characteristics of potatoes were analyzed using the device inclination angle, rotational speed, and the center distance of the separation rollers as test factors. A field trial was carried out to optimize the best combination of factors by taking the rate of injured potatoes, bright potatoes, and skin-breaking rate as the test indexes. The force threshold for skin-breaking injury in potatoes was found to be 190–195 N. When the inclination angle of the device was 6°, the rotation speed of the separation roller was 100 r/min, and the distance between the centers of the separation rollers was 79 mm. The rate of injury was 1.25%, the rate of bright potatoes was 99.01%, and the rate of skin-breaking was 1.58%. When the inclination angle of the device was 8°, the rotational speed of the separating roller was 80 r/min, and the center distance of the separating roller was 79 mm, the rate of injured potato was 1.43%, the rate of bright potato was 98.64%, and the rate of broken skin was 1.77%. This paper offers an optimized reference for the effectual removal of sticky soil.

Structural coloration - i.e. colors arising from light interference in microstructures - is a good resource for several applications but usually involves elaborate fabrication techniques. Here, the authors achieve controllable coloration using silica particles embedded in a rearrangeable polymer network.

Glioblastoma (GBM) is the most common primary malignant tumor in the brain, accounting for 51.4% of all primary brain tumors. GBM has a highly immunosuppressive tumor microenvironment (TME) and, as such, responses to immunotherapeutic strategies are poor. Vaccinia virus (VV) is an oncolytic virus that has shown tremendous therapeutic effect in various tumor types. In addition to its directly lytic effect on tumor cells, it has an ability to enhance immune cell infiltration into the TME allowing for improved immune control over the tumor. Here, we used a new generation of VV expressing the therapeutic payload interleukin-21 to treat murine GL261 glioma models. After both intratumoral and intravenous delivery, virus treatment induced remodeling of the TME to promote a robust anti-tumor immune response that resulted in control over tumor growth and long-term survival in both subcutaneous and orthotopic mouse models. Treatment efficacy was significantly improved in combination with systemic α-PD1 therapy, which is ineffective as a standalone treatment but synergizes with oncolytic VV to enhance therapeutic outcomes. Importantly, this study also revealed the upregulation of stem cell memory T cell populations after the virus treatment that exert strong and durable anti-tumor activity.

Dynamic analysis of a functionally-graded (FG) cylindrical micro shell is investigated in this work. Effect of small parameter in micro scale is included in fundamental relations based on modified couple stress theory (MCST). For more precise analyzing the structure, third-order shear deformation theory (TSDT) is employed as kinematic relations. The shell is made from FG materials, using power function law. A solution procedure based on an analytical method is developed for special boundary condition. The numerical results are computed in graphical form to seek how changes of main parameters of the study such as micro parameter, in-homogeneity index and some geometric values change the free vibration responses. As an important output of this paper, it is concluded that an increase in micro parameter leads to increase of natural frequency. Furthermore, increase of in-homogeneous index yields more soft structure and then decrease of natural frequency.

Background: Enterocytozoon bieneusi is a common enteric pathogen reported in human and many animals. But there are few reports of E. bieneusi in nonhuman primates (NHPs). The aim of this study was to examine the prevalence and molecular characterization of E. bieneusi in NHPs from Northern and Central China. Results: A total of 299 specimens of NHPs were collected. The overall prevalence rate of E. bieneusi was 9.4% (28/299) in NHPs by ribosomal internal transcribed spacer (ITS) amplification, including 10.0% (16/160) in captive NHPs and 8.6% (12/139) in wild NHPs. In captive NHPs, the infection rate was 9.1% in male, 11.5% in female. Infection rate in juvenile ITS (6.7%) was higher than in the adult ITS (5.6%). In different regions, infection rate in Hubei (14.7%) was higher than in Henan (7.6%) and Beijing (7.9%). Five genotypes were found, including 4 known genotypes (D, HND-Ⅰ, EbpC, SHW2) and a novel genotype named NHP1. Genotype D (8/28) and NHP1 (8/28) were the most prevalent, followed by EbpC (6/28), SHW2 (4/28), and HND-Ⅰ (2/28). All the 5 genotypes belonged to zoonotic Group1. Conclusion: These findings could deepen our understanding of E. bieneusi prevalence and genotype distribution in NHPs in China. Our study shows that NHPs may be the reservoir of zoonotic E. bieneusi and might present a potential serious threat.

Abstract Noninvasive genetic sampling greatly facilitates studies on the genetics, ecology, and conservation of threatened species. Species identification is often a prerequisite for noninvasive sampling‐based biological studies. Due to the low quantity and quality of genomic DNA from noninvasive samples, high‐performance short‐target PCR primers are necessary for DNA barcoding applications. The order Carnivora is characterized by an elusive habit and threatened status. In this study, we developed three pairs of short‐target primers for identifying Carnivora species. The COI279 primer pair was suitable for samples with better DNA quality. The COI157a and COI157b primer pairs performed well for noninvasive samples and reduced the interference of nuclear mitochondrial pseudogenes (numts). COI157a could effectively identify samples from Felidae, Canidae, Viverridae, and Hyaenidae, while COI157b could be applied to samples from Ursidae, Ailuridae, Mustelidae, Procyonidae, and Herpestidae. These short‐target primers will facilitate noninvasive biological studies and efforts to conserve Carnivora species.

Abstract The development of multidrug resistance (MDR) during cancer chemotherapy is a major challenge in current cancer treatment strategies. Numerous molecular mechanisms, including increased drug efflux, evasion of drug-induced apoptosis, and activation of DNA repair mechanisms, can drive chemotherapy resistance. Here we have identified the major vault protein (MVP) and the B-cell lymphoma-2 (BCL2) gene as two potential factors driving MDR in esophageal squamous cell carcinoma (ESCC). We have designed a novel and versatile self-assembling nanoparticle (NP) platform on a multifunctional carboxymethyl chitosan base to simultaneously deliver Adriamycin, and siRNAs targeting MVP and BCL2 (CEAMB NPs), thus reducing drug efflux and promoting apoptosis of esophageal cancer cells. To achieve effective delivery to tumor tissues and inhibit tumor growth in vivo, carboxymethyl chitosan was engineered to contain multiple histidines for enhanced cytosol delivery, cholesterol for improved self-assembly, and epidermal growth factor receptor (EGFR) antibodies to target cancer cells. Our results indicate that these nanoparticles are efficiently synthesized with the desired chemical composition to self-assemble into cargo-containing NPs. Furthermore, we have shown that the synthesized NPs will successfully inhibit cancer cells growth and tumor development when delivered to cultured ESCC cells or to in vivo mouse xenograft models. Our engineered NPs offer a potential novel platform in treating various types of chemotherapy-resistant tumors. Graphical Abstract

Abstract Active localization of a stationary target is one key issue in applications of bistatic sonar based on bistatic range (BR) measurement. However, the complex underwater environment makes achieving the synchronization between the transmitted station and the received station difficult. For solving the synchronization problem, this study relies on mobile bistatic sonar to acquire measurement information at multiple time steps. After that, the target location and clock bias are jointly estimated by solving a non‐linear least square problem. To this end, a recursive scheme is proposed to optimise the measurement cost and reduce the impact of the initial value to achieve accurate estimation by taking full advantage of the redundant measurement information. Orthogonal transformation is used to ensure computational efficiency and numerical reliability. The Cramer–Rao Lower Bound (CRLB) is also derived as a lower bound on the error in estimating the target position and clock bias. Simulation results show that the proposed method achieves the CRLB performance and optimises the measurement cost over the small error region under Gaussian noise.

In this paper, a model to predict the residual shear capacity of RAC beams with corroded stirrups was established, and the simulation analysis was conducted on recycled concrete beams with different corrosion level using ANSYS. The reliability of the finite element analysis model was verified by comparing the finite element results with experimental results.

Most scholars believe that transgression events can contribute positively to organic matter enrichment and shale gas sweet spot development, while whether or not regression events are conducive to shale gas sweet spot development remains to be further discussed. Variations in organic carbon content (TOC), and major and trace elements at the Rhuddanian–Aeronian stage in the Luzhou area, the southern margin of Sichuan Basin, were analyzed in this paper. We discuss differences in paleoenvironment organic matter enrichment and shale sweet spot development during transgression and regression. A transgressive system tract (TST) occurred during the early Rhuddanian stage, while early highstand system tracts (Ehst-1 and Ehst-2) occurred during the late Rhuddanian stage and Aeronian stage, and a late highstand system tract (LHST) developed during the late Aeronian stage. A rise in sea level during the TST in the upper Yangtze resulted in an anoxic environment, where a continuous upwelling current brought about a large number of nutrients in the seawater, significantly increasing paleoproductivity. Strong tectonic subsidence, weak chemical weathering, and a rising sea level together led to a low terrigenous debris supply in the catchment area. Therefore, paleoproductivity and redox conditions were the primary controlling factors of organic matter enrichment at the TST stage, with a clastic supply of secondary importance. With the advance of the Guangxi orogeny, the organic matter enrichment at the EHST-1, EHST-2, and LHST stages was mainly controlled by redox conditions and debris supply. A comparison of the key physical parameters and geochemical indicators of shale reservoirs from these four system tracts suggests that two shale sweet spot types (type I and II) were developed during the Rhuddanian–Aeronian stage, occurring in the TST and EHST-2 stages. High TOC and high microcrystalline quartz content are key to developing type I sweet spots, while enhanced anoxic conditions in the bottom water caused by ephemeral, small-scale sea level rises are the main determinant of class II sweet spots in the later EHST stage.

The giant panda, Ailuropoda melanoleuca, serves as a flagship species for biodiversity conservation, embodying the intersection of ecological, evolutionary, and anthropogenic forces shaping the natural world. Hematological parameters serve as crucial indicators for assessing the physiological status of animals. However, our understanding of blood parameters and hemorheology in captive giant pandas under non-anesthetic conditions is limited. In this study, from September 2018 to August 2020, we collected blood samples from captive giant pandas under non-anesthetic conditions. Twelve captive giant pandas, ranging in age from 2 to 28 years, were divided into three groups based on their age, and the variations in basic blood parameters and hemorheological parameters across four seasons were analyzed. This provided baseline data for future blood sample comparisons in non-anesthetized captive giant pandas. Additionally, we observed seasonal changes in hematological morphology, hemorheology, and serum enzymes. Moreover, seasonality had a regulatory effect on hemorheological parameters and negatively impacted blood viscosity. Age influenced changes in serum enzymes, serum protein content, and serum metabolites, indicating differences in overall metabolic processes among giant pandas of different age groups. Whether factors such as season and climate contribute to environmental stress in captive giant pandas requires further investigation. The findings of this study may help to protect the stability of the giant panda population better and provide a reference for the medical care of captive giant pandas.

The fish pump is an important piece of power equipment for aquaculture, especially for deep-sea engineering vessels and cage culture. Fish pump research focuses on reducing fish body damage, improving survival rates, and increasing fish lifting efficiency. The research object in this paper is a new type of vacuum fish pump, with the aim of improving the hydraulic performance of the vacuum fish pump and reducing the damage to the fish body. The dependent variables include the dynamic change process of the flow state and flow field under diachronic conditions, the fluid simulation analysis of the vacuum pump body and the flow channel structure, the inlet flow rate of the fish pump, the negative pressure of the pipeline, and the impact force of the water flow on the inner wall of the tank. The independent variables include the operating conditions of the pump body and the fish pump. The Latin hypercube sampling method is used to extract 167 sets of calculation models for the independent variables, and multi-objective optimization is performed based on the NSGA-II algorithm for the hydrodynamic performance of the fish pump. On the basis of ensuring the fish body damage rate, the structural parameters of the vacuum fish pump with the optimal hydrodynamic performance under 167 sets of parameter values were obtained. The optimized parameters were then entered into the solver again, and the results showed that, in the optimal structural parameters under certain conditions, the direction of the incident water flow in the vacuum fish pump tank is close to the upper end of the tank body, which will reduce the speed of the fish-water mixed flow when entering the tank, thereby reducing the collision damage to the fish body. Currently, the water flow velocity at the water inlet is about 2.5 m/s, and the negative pressure value distribution gradient between the tank body and the water inlet pipeline is quite consistent, which can achieve good fish suction and fish lifting effects.

Abstract Background Prairie grass (Bromus catharticus) is a typical cool-season forage crop with high biomass production and fast growth rate during winter and spring. However, its genetic research and breeding has remained stagnant due to limited available genomic resources. The aim of this study was to generate large-scale genomic data using high-throughput transcriptome sequencing, and perform a preliminary validation of EST-SSR markers of B. catharticus. Results Eleven tissue samples including seeds, leaves, and stems were collected from a new high-yield strain of prairie grass BCS1103. A total of 257,773 unigenes were obtained, of which 193,082 (74.90%) were annotated. Comparison analysis between tissues identified 1803, 3030, and 1570 genes specifically and highly expressed in seed, leaf, and stem, respectively. A total of 37,288 EST-SSRs were identified from unigene sequences, and more than 80,000 primer pairs were designed. We synthesized 420 primer pairs and selected 52 ones with high polymorphisms to estimate genetic diversity and population structure in 24 B. catharticus accessions worldwide. Despite low diversity indicated by an average genetic distance of 0.364, the accessions from South America and Asia and wild accessions showed higher genetic diversity. Moreover, South American accessions showed a pure ancestry, while Asian accessions demonstrated mixed internal relationships, which indicated a different probability of gene flow. Phylogenetic analysis clustered the studied accessions into four clades, being consistent with phenotypic clustering results. Finally, Mantel analysis suggested the total phenotypic variation was mostly contributed by genetic component. Stem diameter, plant height, leaf width, and biomass yield were significantly correlated with genetic data (r > 0.6, P

Widely distributed in the alpine sandy grassland in east Qinghai-Tibet Plateau (QTP), Kengyilia melanthera is considered as an ideal pioneer grass for the restoration of degraded and desertification grassland in the region. Under the special ecological and climatic conditions in the northwest Sichuan plateau located in east QTP, it is of great significance to optimize the amount of nitrogen fertilizer for the seed production of this species. The impact of nitrogen (N) fertilizer application on seed yield and quality of K. melanthera ‘Aba’, the only domesticated variety in the Kengyilia genus of Poaceae, was investigated based on two-year field experiments in the northwestern Sichuan plateau. The results showed that with the increase of N fertilizer application, the number of tillers, number of fertile tillers, 1,000-seed weight and seed yield of this species increased likewise. The optimum N fertilizer rate deduced in the present study was 180 kg·hm−2, where the number of fertile tillers 1,000-seed weight and seed yield reached the peak values. Interestingly, the standard germination rate, germination energy, accelerated aging germination rate, dehydrogenase and acid phosphatase activity of seeds were not affected by the increasing the input of N fertilizer. The comprehensive evaluation of membership function showed that the optimal N fertilizer treatment was 180 kg·hm−2 both for 2016 and 2017. This study provided a certain practical suggestion for the improvement of seed production of K. melanthera in the northwest Sichuan plateau.

Abstract Cataracts are a common cause of visual impairment and blindness in mammals. They are usually associated with aging, but approximately one third of cases have a significant genetic component. Cataracts are increasingly prevalent among aging populations of captive giant pandas (Ailuropoda melanoleuca) and it is therefore important to identify genetic determinants that influence the likelihood of cataract development in order to distinguish between congenital and age-related disease. Here we screened for cataract-related genetic effects using a functional candidate gene approach combined with bioinformatics to identify the underlying genetic defect in a giant panda with congenital cataracts. We identified a missense mutation in exon 10 of the HSF4 gene encoding heat shock transcription factor 4. The mutation causes the amino acid substitution R377W in a highly conserved segment of the protein between the isoform-specific and downstream hydrophobic regions. Predictive modeling revealed that the substitution is likely to increase the hydrophobicity of the protein and disrupt interactions with spatially adjacent amino acid side chains. The mutation was not found in 13 unaffected unrelated animals but was found in an unrelated animal also diagnosed with senile congenital cataract. The novel missense mutation in the HSF4 gene therefore provides a potential new genetic determinant that could help to predict the risk of cataracts in giant pandas.

Abstract Background Aberrant activation of the Wnt/β-catenin signaling pathway is one of the most frequent abnormalities in human cancer, including colorectal cancer (CRC). Previous studies revealed pivotal functions of WNT family members in colorectal cancer, as well as their prognostic values. Nevertheless, the prognostic role and mechanisms underlying WNT7b in colorectal cancer development remains unclear. Methods In this study, WNT7b expression was measured by immunohistochemical staining of 100 cases of surgically resected human colorectal cancerous tissues as well as matched adjacent normal tissues constructed as tissue microarrays. In vitro studies, we attempted to substantiate the WNT7b expressional pattern previously found in immunohistochemistry staining. We used the colorectal cancer cell-line HCT116 and normal colorectal cell-line FHC for immunofluorescence staining and nuclear/cytoplasmic separated western blotting. We measured epithelial–mesenchymal transition (EMT) markers and migration capacity of HCT116 in the context of WNT7b knocked-down using short interfering RNA. Finally, clinical and prognostic values of WNT7b activation levels were examined. Results WNT7b was expressed in the nucleus in adjacent normal tissues. In CRC tissues, nuclear expression of WNT7b was similar; however, membrane and cytoplasmic expression was strikingly enhanced. Consistently, in vitro analysis confirmed the same expression pattern of WNT7b. Compared with FHC cells, HCT116 cells displayed higher levels of WNT7b membrane and cytoplasmic enrichment, as well as higher migration capacity with a sensitized EMT process. Either partial knockdown of WNT7b or blockade of the Wnt/β-catenin signaling pathway reversed EMT process and inhibited the migration of HCT116 cells. Finally, elevated secretion levels of WNT7b were significantly associated with lymphatic and remote metastasis and predicted worse prognosis in the CRC cohort. Conclusion In summary, we demonstrated that the activation of WNT7b autocrine probably contributes to CRC metastasis by triggering EMT process through the Wnt/β-catenin signaling pathway. High levels of WNT7b autocrine secretion predicts poor outcome in patients with CRC. This molecule is a promising candidate for clinical CRC treatments.

Abstract Background Cataracts are defects of the lens that cause progressive visual impairment and ultimately blindness in many vertebrate species. Most cataracts are age-related, but up to one third have an underlying genetic cause. Cataracts are common in captive zoo animals, but it is often unclear whether these are congenital or acquired (age-related) lesions. Results Here we used a functional candidate gene screening approach to identify mutations associated with cataracts in a captive giant panda (Ailuropoda melanoleuca). We screened 11 genes often associated with human cataracts and identified a novel missense mutation (c.686G > A) in the MIP gene encoding major intrinsic protein. This is expressed in the lens and normally accumulates in the plasma membrane of lens fiber cells, where it plays an important role in fluid transport and cell adhesion. The mutation causes the replacement of serine with asparagine (p.S229N) in the C-terminal tail of the protein, and modeling predicts that the mutation induces conformational changes that may interfere with lens permeability and cell–cell interactions. Conclusion The c.686G > A mutation was found in a captive giant panda with a unilateral cataract but not in 18 controls from diverse regions in China, suggesting it is most likely a genuine disease-associated mutation rather than a single-nucleotide polymorphism. The mutation could therefore serve as a new genetic marker to predict the risk of congenital cataracts in captive giant pandas.

This study aimed to investigate the effects of different water velocities on the growth performance, blood physiology, and digestive capacity of coral trout (Plectropomus leopardus) in a Recirculating aquaculture system (RAS). One hundred and twenty healthy, uniformly sized coral trout (body mass (92.01 ± 8.04) g; body length (15.40 ± 0.65) cm) were randomly assigned to three flow velocity groups (1 bl/s, 2 bl/s, and 2.5 bl/s) and one control group (0 bl/s). The results show that the weight gain rate (WGR) and specific growth rate (SGR) of coral trout in the 2.5 bl/s water flow velocity group were significantly lower than those in the control group and 1 bl/s water flow velocity group (p < 0.05), while their feed coefficient (FC) values were significantly higher than those of the control group and 1 bl/s water flow velocity group (p < 0.05). The blood glucose (GLU) concentration of coral trout in the 2 bl/s water flow velocity group and the 2.5 bl/s water flow velocity group significantly decreased compared to those in the control group (p < 0.05), while the lactic acid (LD) concentration increased. As the cortisol (COR) concentration and lipase (LPS) enzyme activity of coral trout did not significantly change (p > 0.05), the α- AMS enzyme activity significantly decreased (p < 0.05). Under 2.5 bl/s water flow velocity, the intestinal structure of coral trout changed, and the number of goblet cells decreased. High-water flow velocities affect the physiological homeostasis and intestinal digestion of coral trout, resulting in a decrease in their growth performance, indicating that coral trout is more sensitive to high-water flow velocities. In actual RAS aquaculture, the flow rate should be controlled within 1 bl/s.

Background Blood pressure and tissue perfusion are controlled in part by the level of intrinsic (myogenic) arterial tone. However, many of the molecular determinants of this response are unknown. We previously found that mice with targeted disruption of the gene encoding the angiotensin II type 1a receptor (AT1AR) (Agtr1a), the major murine angiotensin II type 1 receptor (AT1R) isoform, showed reduced myogenic tone; however, uncontrolled genetic events (in this case, gene ablation) can lead to phenotypes that are difficult or impossible to interpret. Methods and Results We tested the mechanosensitive function of AT1R using tamoxifen‐inducible smooth muscle‐specific AT1aR knockout (smooth muscle‐Agtr1a−/−) mice and studied downstream signaling cascades mediated by Gq/11 and/or β‐arrestins. FR900359, Sar1Ile4Ile8‐angiotensin II (SII), TRV120027 and TRV120055 were used as selective Gq/11 inhibitor and biased agonists to activate noncanonical β‐arrestin and canonical Gq/11 signaling of the AT1R, respectively. Myogenic and Ang II‐induced constrictions were diminished in the perfused renal vasculature, mesenteric and cerebral arteries of smooth muscle‐Agtr1a−/− mice. Similar effects were observed in arteries of global mutant Agtr1a−/− but not Agtr1b−/− mice. FR900359 decreased myogenic tone and angiotensin II‐induced constrictions whereas selective biased targeting of AT1R‐β‐arrestin signaling pathways had no effects. Conclusions This study demonstrates that myogenic arterial constriction requires Gq/11‐dependent signaling pathways of mechanoactivated AT1R but not G protein‐independent, noncanonical pathways in smooth muscle cells.

Rhesus macaques (Macaca mulatta) are the most widely distributed species of Old World monkey and are frequently used as animal models to study human health and disease. Their gastrointestinal microbial community likely plays a major role in their physiology, ecology and evolution. Herein, we compared the fecal microbiome and antibiotic resistance genes in 15 free-ranging and 81 zoo-captive rhesus macaques sampled from two zoos in China, using both 16S amplicon sequencing and whole genome shotgun DNA sequencing approaches. Our data revealed similar levels of microbial diversity/richness among the three groups, although the composition of each group differed significantly and were particularly marked between the two zoo-captive and one wild groups. Zoo-captive animals also demonstrated a greater abundance and diversity of antibiotic genes. Through whole genome shotgun sequencing we also identified a mammalian (simian) associated adenovirus. Overall, this study provides a comprehensive analysis of resistomes and microbiomes in zoo-captive and free-ranging monkeys, revealing that semi-captive wildlife might harbor a higher diversity of antimicrobial resistant genes.

Formation water is produced during gas well production, which can seriously affect gas well productivity, especially in deep and ultradeep tight sandstone gas reservoirs. In this paper, we have studied the formation water production and geochemical properties of the ultradeep tight sandstone gas reservoir in the Cretaceous Bashijiqike Formation of the DK gas field in the Kuqa Depression. The results indicate that the formation water can be classified as condensate water, gas-water transition zone water, mixed water, and isolated formation water, all of which are acidic and of CaCl2 type, with increasing salinity or chloride ion content. Sodium/chloride ratio (ρNa+/ρCl-), metamorphic coefficient (ρ(Cl--Na+)/ρ(Mg2+)), desulfurization coefficient (100×ρSO42−/ρCl−), and trace elements concentration parameters show that the formation water was formed in a closed and reductive environment and experienced strong water-rock interaction. The formation water may have been influenced by early seawater, but it is not significant and is more likely to have been influenced by water seepage from the overlying gypsum strata. The Sr, H, and O isotopes reveal that the different types of formation water have good homology and are not affected by atmospheric precipitation, which is propitious to the preservation of natural gas.

Corynebacterium glutamicum is one of the important industrial microorganisms for production of amino acids and other value-added compounds. Most expression vectors used in C. glutamicum are based on inducible promoter (Ptac or Ptrc) activated by isopropyl-β-D-thiogalactopyranoside (IPTG). However, these vectors seem unsuitable for large-scale industrial production due to the high cost and toxicity of IPTG. Myo-inositol is an ideal inducer because of its non-toxicity and lower price. In this study, a myo-inositol-inducible expression vector pMI-4, derived from the expression vector pXMJ19, was constructed. Besides the original chloramphenicol resistance gene cat, multiple cloning sites, and rrnB terminator, the pMI-4 (6,643 bp) contains the iolRq cassette and the myo-inositol-inducible promoter PiolT1. The pMI-4 could stably replicate in the C. glutamicum host. Meanwhile, the non-myo-inositol degradation host strain C. glutamicumΔiolGΔoxiCΔoxiDΔoxiE for maintaining the pMI-4 was developed. Overexpression of hemAM and hemL using pMI-4 resulted in a significant accumulation of 5-aminolevulinic acid, indicating its potential application in metabolic engineering and industrial fermentation.

Multiple-replicon resistance plasmids have become important carriers of resistance genes in Gram-negative bacteria, and the evolution of multiple-replicon plasmids is still not clear. Here, 56 isolates of Klebsiella isolated from different wild animals and environments between 2018 and 2020 were identified by phenotyping via the micro-broth dilution method and were sequenced and analyzed for bacterial genome-wide association study. Our results revealed that the isolates from non-human sources showed more extensive drug resistance and especially strong resistance to ampicillin (up to 80.36%). The isolates from Malayan pangolin were particularly highly resistant to cephalosporins, chloramphenicol, levofloxacin, and sulfamethoxazole. Genomic analysis showed that the resistance plasmids in these isolates carried many antibiotic resistance genes. Further analysis of 69 plasmids demonstrated that 28 plasmids were multiple-replicon plasmids, mainly carrying beta-lactamase genes such as blaCTX–M–15, blaCTX–M–14, blaCTX–M–55, blaOXA–1, and blaTEM–1. The analysis of plasmids carried by different isolates showed that Klebsiella pneumoniae might be an important multiple-replicon plasmid host. Plasmid skeleton and structure analyses showed that a multiple-replicon plasmid was formed by the fusion of two or more single plasmids, conferring strong adaptability to the antibiotic environment and continuously increasing the ability of drug-resistant isolates to spread around the world. In conclusion, multiple-replicon plasmids are better able to carry resistance genes than non-multiple-replicon plasmids, which may be an important mechanism underlying bacterial responses to environments with high-antibiotic pressure. This phenomenon will be highly significant for exploring bacterial resistance gene transmission and diffusion mechanisms in the future.

Stem-like cells of various origins showed therapeutic effect to improve the recovery of spinal cord injuryWe, the Editors and Publisher of the journal Artificial Cells, Nanomedicine, and Biotechnology, have retracted the following article:Jian Kang, Chenglin Zhang, Zhongzheng Zhi, Yingjie Wang, Jingdong Liu, Furong Wu & Guanghui Xu (2020) Stem-like cells of various origins showed therapeutic effect to improve the recovery of spinal cord injury, Artificial Cells, Nanomedicine, and Biotechnology, 48:1, 627–638, DOI: 10.1080/21691401.2020.1725031Following publication of this article, concerns about the scientific integrity of the article were brought to the Publisher and Editor’s attention.Whilst the authors were fully cooperative with the investigation and able to answer some questions, they were unable to provide the original western blot data.In addition, concerns remain about the methods used for the animal experiments. As these concerns directly impact the reported results and conclusions, the Editor and Publisher have agreed to retract the article to ensure correction of the scholarly record. The corresponding author has been informed. The authors do not agree with the retraction.We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Abstract Background Accurate identification of potential interactions between drugs and protein targets is a critical step to accelerate drug discovery. Despite many relative experimental researches have been done in the past decades, detecting drug-target interactions (DTIs) remains to be extremely resource-intensive and time-consuming. Therefore, many computational approaches have been developed for predicting drug-target associations on a large scale. Results In this paper, we proposed an deep learning-based method to predict DTIs only using the information of drug structures and protein sequences. The final results showed that our method can achieve good performance with the accuracies up to 92.0%, 90.0%, 92.0% and 90.7% for the target families of enzymes, ion channels, GPCRs and nuclear receptors of our created dataset, respectively. Another dataset derived from DrugBank was used to further assess the generalization of the model, which yielded an accuracy of 0.9015 and an AUC value of 0.9557. Conclusion It was elucidated that our model shows improved performance in comparison with other state-of-the-art computational methods on the common benchmark datasets. Experimental results demonstrated that our model successfully extracted more nuanced yet useful features, and therefore can be used as a practical tool to discover new drugs. Availability http://deeplearner.ahu.edu.cn/web/CnnDTI.htm.

Abstract Background The mammalian major histocompatibility complex (MHC) harbours clusters of genes associated with the immunological defence of animals against infectious pathogens. At present, no complete MHC physical map is available for any of the wild ruminant species in the world. Results The high-density physical map is composed of two contigs of 47 overlapping bacterial artificial chromosome (BAC) clones, with an average of 115 Kb for each BAC, covering the entire addax MHC genome. The first contig has 40 overlapping BAC clones covering an approximately 2.9 Mb region of MHC class I, class III, and class IIa, and the second contig has 7 BAC clones covering an approximately 500 Kb genomic region that harbours MHC class IIb. The relative position of each BAC corresponding to the MHC sequence was determined by comparative mapping using PCR screening of the BAC library of 192,000 clones, and the order of BACs was determined by DNA fingerprinting. The overlaps of neighboring BACs were cross-verified by both BAC-end sequencing and co-amplification of identical PCR fragments within the overlapped region, with their identities further confirmed by DNA sequencing. Conclusions We report here the successful construction of a high-quality physical map for the addax MHC region using BACs and comparative mapping. The addax MHC physical map we constructed showed one gap of approximately 18 Mb formed by an ancient autosomal inversion that divided the MHC class II into IIa and IIb. The autosomal inversion provides compelling evidence that the MHC organizations in all of the ruminant species are relatively conserved.

Kengyilia melanthera is one of the most important forages, and has received significant attention as a desirable ecological pioneer grass for conserving grasslands and mitigating degradation pressure in a region. It is widely distributed in the alpine sandy meadow zone of the Eastern Qinghai–Tibet Plateau (QTP). Therefore, determining the optimal harvest time of this species is critical. A two-year field experiment (2016–2017) was utilized in this study to evaluate the impact of eight harvest times on the seed yield and quality of K. melanthera ‘Aba’. The results show that the fresh weight (FW), dry weight (DW), seed yield (SY), thousand-grain weight (TGW), accelerated aging germination percentage (AAGP), and dehydrogenase activity (DA) of seeds increased with the extension of harvest time in two trial years, while the water content (WC) of seeds decreased. In both trial years, the germination percentage (GEP), germination potential (GP), and acid phosphatase activity (APA) of seeds increased initially and then decreased with the extension of harvest time. The comprehensive evaluation of the membership function and hierarchical clustering revealed that the 30th day after peak anthesis was the optimal harvest time for both 2016 and 2017. During this time, FW, DW, SY, TGW, AAGP, DA, WC, GEP, GP, and APA reached their optimal value, with 0.815 g, 0.518 g, 1773.67 kg·hm−2, 143.81%, 66%, 16.23 µg·mL−1, 36.01%, 87%, 85%, and 2.50 nmol·min−1 in 2016 and 0.805 g, 0.515 g, 1847.42 kg·hm−2, 133.96%, 65%, 16.52 µg·mL−1, 36.04%, 86.5%, 83.5%, and 2.55 nmol·min−1 in 2017, respectively. This study uncovers several high-efficiency and long-term technological solutions for cultivating high yields and quality production of K. melanthera in East QTP.

To maximize the utilization of ocean resources, shorten the return period of investment and directly supply energy to the fishing cage, this paper performs a preliminary study for a state-of-the-art concept integrating a floating offshore wind turbine with a fishing cage. An octagonal semisubmersible rigid fishing cage with a slack catenary mooring system is designed to match the NREL 5 MW offshore baseline wind turbine. Combined with the blade pitch controller, fully coupled aero-hydro-elastic-servo-mooring simulations are performed through FAST and AQWA to explore the dynamic performance of the integrated system. Free decay conditions, uniform wind with irregular and regular waves, and turbulent wind with irregular waves are tested. The results showed that the integrated system works normally at the operating conditions and exhibits different dynamic characteristics for various scenarios. Additionally, the study on the influence of mooring line length indicates that the increasing line length can significantly affect the cage surge motion and the maximum and mean values of the upwind line tension at fairlead. Specifically, the maximum surge motion with a 924-m-long line is 404.8% larger than that with an 880-m-long line. When the line length increases by 5%, the maximum and mean line tensions decrease by 45.7% and 47.7%, respectively, while when the line length increases by 10%, the maximum and mean line tension decrease by 52.9% and 54.2%, respectively. It should be noted that the main purpose of this work is to conduct a preliminary study on this integrated system, aiming to provide an idea for the conceptual design, modeling and simulation analysis of this integrated system.

Neural stem cell (NSC) damage has been reported in patients with Alzheimer’s disease. Intracellular Aβ plays a vital role in NSC damage. Heparan sulfate proteoglycans are potent mediators of Aβ enrichment in the brain. We hypothesized the heparan sulfate proteoglycan glypican 4 (Gpc4) regulates Aβ internalization by NSCs. We evaluated Gpc4 expression in NSCs from P0–P2 generations using immunofluorescence. Adenovirus and lentivirus were used to regulate Gpc4 expression in NSCs and APP/PS1 mice, respectively. Co-immunoprecipitation was used to determine the relationship between Gpc4, Aβ, and low-density lipoprotein receptor-related protein 1 (LRP1). Intracellular Aβ concentrations were detected using enzyme-linked immunosorbent assay and immunofluorescence. The role of Gpc4/LRP1 on toxic/physical Aβ-induced effects was evaluated using the JC-1 kit, terminal deoxynucleotidyl transferase dUPT nick end labeling, and western blotting. Gpc4 was stably expressed in NSCs, neurons, and astrocytes. Gpc4 was upregulated by Aβ in NSCs and regulated Aβ internalization. Gpc4 attenuation reduced Aβ uptake; Gpc4 overexpression increased Aβ uptake. Gpc4 regulated Aβ internalization through LRP1 and contributed to Aβ internalization and toxic/physical concentrations of Aβ-induced mitochondrial membrane potential and cell apoptosis, partly via LRP1. Therefore, Gpc4 is a key regulator of Aβ enrichment in NSCs. Inhibiting Gpc4 rescued the Aβ-induced toxic effect and attenuated the nontoxic Aβ enrichment into intracellular toxic concentrations. Gpc4 contributed to Aβ internalization and toxic/physical concentrations of Aβ-induced mitochondrial membrane potential damage and cell apoptosis, partly via LRP1. These findings suggest a potential role of Gpc4 in treating Alzheimer’s disease at an early stage, by targeting NSCs.

Fluorescent sensors that respond to environmental conditions (temperature, pressure, and pH) have attracted widespread attention in recent years. Generally, traditional solid-state fluorescent materials tend to suffer from aggregation-induced quenching (ACQ) and difficulty of film forming, limiting their extensive applications. Therefore, researchers are focusing more and more attention on fluorescent sensors with aggregation-induced emission (AIE) effects. Herein, the article reports an AIE molecule (TPEBZMZ) containing tetraphenylethylene (TPE) and benzimidazole fragments. The fluorescence properties of TPEBZMZ in solution and aggregation states have been investigated, and the luminescence performance and aggregation structures of solid-state TPEBZMZ after force and acid treatments have been explored. The results show obvious AIE and fluorescent sensing properties of TPEBZMZ, presenting force- and acid-induced discolorations. Moreover, the TPEBZMZ-based fluorescent nanofibrous film is fabricated by electrospinning the solution of TPEBZMZ blended with polylactic acid (PLA), which shows a good nanofiber film structure and exhibits reversible acid-induced discoloration property, even with only 0.5 wt% TPEBZMZ. This work provides a simple strategy to achieve stimulus-responsive fluorescent film.

Gyrostigma rhinocerontis (Diptera: Oestridae) is a rare obligate intestinal parasite of both white and black rhinoceroses, which can induce severe myiasis, cause secondary infection, and lead to enormous economic and scientific loss. Antennae are the main sensory organs of G. rhinocerontis, which may have evolved a series of specialized adaptive structures to facilitate the exploitation of their hosts. Here, we thoroughly examine the antennae of G. rhinocerontis via light and scanning electron microscopy. Only microtrichia and chaetic sensilla were observed on the scape and pedicel, and the latter is enlarged, half-enveloping the postpedicel. Four types of sensilla (trichoid sensilla, basiconic sensilla, coeloconic sensilla, and clavate sensilla) and sensory pits are detected on the postpedicel. A set of coeloconic sensilla and a chaetic sensillum are located on the arista. Distribution, type, size, and ultrastructure of antennal sensilla are presented. The antennae of G. rhinocerontis are the largest among Oestridae species, with the most sensilla and the most sensory pits. These antennal characteristics could be correlated to their adaptation for more sensitive and accurate olfactory organs, used to locate their rare and endangered hosts. Accordingly, this morphological evidence supports that the host is an important driving factor in the diversity of antennal morphology in the bot flies.

Due to its drug resistant nature, β-lactamase represents a serious challenge for public health. Extended-spectrum β-lactamase (ESBL) producing Klebsiella pneumoniae clones are increasingly reported worldwide. Little is known about the prevalence and biological characteristics of drug-resistant strains in zoos. During routine surveillance at the Zhengzhou Zoo of China, we found Klebsiella pneumoniae isolate in healthy Red Kangaroos (Macropus Rufus) with severe MDR. The Klebsiella pneumoniae were especially resistant to Cefuroxime Sodium (MIC, > 64 μg/mL), Ceftriaxone (MIC, >8 μg/mL) and Cefepime (MIC, >64 μg/mL), and belonged to ST290. Subsequently, whole genome sequencing (WGS) showed that the Chrome Chr-M297-1 harbored blaDHA–3, blaSHV–1, blaCTX–M–14, fosA5, dfrA3, sul3, etc., and pM297-1.1 [222,864 bp, IncFIB(K)], which carried nine antimicrobial genes including blaCTX–M–14, blaTEM–191, aph(3″)-Ib, aph(6)-Id and qnrS1, etc., and pM297-1.2 [225,763 bp, IncFII(K)] carried 22 antimicrobial genes including blaTEM–1, blaCTX–M–3, aph(3′)-Ia, aac(3)-IIa, aac(6′)-Ib-cr, aadA16, qnrB2, qnrS1, qacEΔ1, mphA, sul1, and dfrA27, etc. A traceability analysis then revealed that these two plasmids were highly similar to those recovered from human clinical samples in some southern cities in Sichuan Province, China (>99%), suggesting that these plasmids are spreading in China. Furthermore, two plasmids harboring conjugal transfer genes facilitated the transmission of antimicrobial genes by conjugation with E. coli J53. Our research shows that the transmission and adaptation of Klebsiella pneumoniae producing ESBLs is occurring in zoo environments, suggesting that zoos may be becoming important potential reservoirs for clinically important drug-resistant genes. It is therefore necessary to monitor the emergence and spread of drug-resistant gene strains in captive wild animals held in zoo environments.

Salt stress negatively affects plant growth and crop productivity. As an ideal model pathway of salt tolerance in glycophyte. To better understand the molecular mechanisms of salt-response in glycophyte, 466 of 15,768 Arabidopsis thaliana proteins with the GO term of biological with known genetic background, Arabidopsis thaliana has been widely applied to disclose the process ‘response to salt stress’ were retrieved from UniPort and analyzed by bioinformatics tools of PANTHER, DAVID, KEGG, Cytoscape and STRING. Our results not only indicated the involvement of salt-responsive proteins in various pathways and interaction networks, but also demonstrated the more complicated cross-tolerances to both abiotic stresses (osmosis, water deprivation, abscisic acid, cold, heat, light and wounding) and biotic stresses (bacterium and fungus) and multiple subcellular locations of these salt-responsive proteins. Furthermore, protein activities of superoxide dismutase (SOD) and peroxidase (POD) in Arabidopsis thaliana were determined under salt, cold and osmotic stresses, which validated the hypothesis of cross-tolerance to multiple stresses. Our work will greatly improve the current knowledge of salt tolerance mechanism in glycophytes and provide potential salt-responsive candidates for promoting plant growth and increasing crop output.

Abstract Background In the assisted reproduction, the infertile molecules of spermatozoa from normozoospermic men who underwent the unexplained failure of in vitro fertilization (IVF) due to the lack of sperm binding to the normal zona pellucida, and then achieved pregnancy with the rescue intracytoplasmic sperm injection (R-ICSI) remain unclear. More works are still necessary to explore this male infertile mechanism. Methods Normozoospermicmen with the IVF pregnancy and normozoospermic men with the R-ICSI pregnancy after the conventional IVF failure were collected. iTRAQ-based proteomic approach were performed to reveal the new infertile causes between the IVF pregnancy men and the R-ICSI pregnancy men. To validate the confidence of proteome data, the individual samples were analyzed by western blot and immunofluorescence. Further, the spontaneous acrosome reactions were measured to evaluate the sperm quality. Results Compared with IVF pregnancy group, 56 sperm proteins were differentially expressed in the R-ICSI pregnancy group. Bioinformatic analyses (PANTHER, DAVID, PubMed and STRING) indicated these altered sperm proteins were involved in various molecular functions: reproduction, chromosome organization, and sperm-oocyte interaction. Moreover, the confidence of proteome data was confirmed by western blot and immunofluorescence using the individual samples, which were consistent with our proteomic data. Additionally, an increased rate of the spontaneous acrosome reaction rate was found in the R-ICSI pregnancy group. Conclusions The sealtered sperm proteins and the increased spontaneous acrosome reaction rate might account for this unexplained male infertility in the R-ICSI pregnancy patients. The present proteomic results will throw light on the better understanding of the unexplained infertile mechanisms underlying these normozoospermic man who achieved R-ICSI pregnancy after IVF failure.

Abstract Background Malaria parasites and related haemosporidian parasites are widespread and may cause severe diseases in birds. These pathogens should be considered in projects aiming breeding of birds for purposes of sustained ex situ conservation. Cranes are the ‘flagship species’ for health assessment of wetland ecosystems, and the majority of species are endangered. Malaria parasites and other haemosporidians have been reported in cranes, but the host-parasite relationships remain insufficiently understood. Morbidity of cranes due to malaria has been reported in Beijing Zoo. This study report prevalence, diversity and distribution of malaria parasites and related haemosporidians in cranes in Beijing Zoo and suggest simple measures to protect vulnerable individuals. Methods In all, 123 cranes (62 adults and 61 juveniles) belonging to 10 species were examined using PCR-based testing and microscopic examination of blood samples collected in 2007–2014. All birds were maintained in open-air aviaries, except for 19 chicks that were raised in a greenhouse with the aim to protect them from bites of blood-sucking insects. Bayesian phylogenetic analysis was used to identify the closely related avian haemosporidian parasites. Results Species of Plasmodium (5 lineages), Haemoproteus (1) and Leucocytozoon (2) were reported. Malaria parasites predominated (83% of all reported infections). The overall prevalence of haemosporidians in juveniles was approximately seven-fold higher than in adults, indicating high susceptibility of chicks and local transmission. Juvenile and adult birds hosted different lineages of Plasmodium, indicating that chicks got infection from non-parent birds. Plasmodium relictum (pSGS1) was the most prevalent malaria parasite. Mortality was not reported in adults, but 53% of infected chicks died, with reports of co-infection with Plasmodium and Leucocytozoon species. All chicks maintained in the greenhouse were non-infected and survived. Species of Leucocytozoon were undetectable by commonly used PCR protocol, but readily visible in blood films. Conclusion Crane chicks often die due to malaria and Leucocytozoon infections, which they likely gain from wild free-living birds in Beijing Zoo. Molecular diagnostics of crane Leucocytozoon parasites needs improvement. Because the reported infections are mainly chick diseases, the authors recommend maintaining of juvenile birds in vector-free facilities until the age of approximately 6 months before they are placed in open-air aviaries.