Search

Abstract Background Due to its unique anatomical characteristics, supracondylar fractures of the humerus are often difficult to achieve firm fixation with internal fixation equipment, resulting in delayed functional exercise, often leaving cubitus varus deformity, elbow stiffness, contractures, and other complications. Here, we report an adult patient with a supracondylar fracture of the humerus who underwent internal fixation through an anterior median incision in the humerus with our self-developed anterior anatomical locking plate of the distal humerus. Case presentation A 29-year-old male patient of Chinese ethnicity with trauma-induced right supracondylar fracture of the humerus and multiple soft tissue contusions, without nerve damage, blood vessel damage, or other injuries, underwent an internal incision in our hospital using a new anatomical locking plate for the anterior distal humerus fixed treatment. During the 16-month follow-up period, the patient’s elbow range of motion was almost completely restored, functional scores were excellent, and there were no minor or major postoperative complications. Conclusion In this study, we propose a surgical reconstruction strategy for adult patients with supracondylar humeral fractures. Through the anterior median incision of the humerus, open reduction and internal fixation were performed with an anatomic locking plate on the anterior side of the distal humerus to restore and fix the structure of the distal humerus, and satisfactory clinical results were achieved in our case.

Abstract Background Chicken coccidiosis is a protozoan disease that leads to considerable economic losses in the poultry industry. Live oocyst vaccination is currently the most effective measure for the prevention of coccidiosis. However, it provides limited protection with several drawbacks, such as poor immunological protection and potential reversion to virulence. Therefore, the development of effective and safe vaccines against chicken coccidiosis is still urgently needed. Methods In this study, a novel oral vaccine against Eimeria tenella was developed by constructing a recombinant Lactobacillus plantarum (NC8) strain expressing the E. tenella RON2 protein. We administered recombinant L. plantarum orally at 3, 4 and 5 days of age and again at 17, 18 and 19 days of age. Meanwhile, each chick in the commercial vaccine group was immunized with 3 × 102 live oocysts of coccidia. A total of 5 × 104 sporulated oocysts of E. tenella were inoculated in each chicken at 30 days. Then, the immunoprotection effect was evaluated after E. tenella infection. Results The results showed that the proportion of CD4+ and CD8+ T cells, the proliferative ability of spleen lymphocytes, inflammatory cytokine levels and specific antibody titers of chicks immunized with recombinant L. plantarum were significantly increased (P

ABSTRACT E3 ubiquitin ligase (E3) plays a vital role in regulating inflammatory responses by mediating ubiquitination. Previous studies have shown that ankyrin repeat and SOCS box-containing protein 3 (ASB3) is involved in immunomodulatory functions associated with cancer. However, the impact of ASB3 on the dynamic interplay of microbiota and inflammatory responses in inflammatory bowel disease (IBD) is unclear. Here, we systematically identify the E3 ligase ASB3 as a facilitative regulator in the development and progression of IBD. We observed that ASB3 exhibited significant upregulation in the lesions of patients with IBD. ASB3−/− mice are resistant to dextran sodium sulfate-induced colitis. IκBα phosphorylation levels and production of proinflammatory factors IL-1β, IL-6, and TNF-α were reduced in the colonic tissues of ASB3−/− mice compared to WT mice. This colitis-resistant phenotype was suppressed after coprophagic microbial transfer and reversed after combined antibiotics removed the gut commensal microbiome. Mechanistically, ASB3 specifically catalyzes K48-linked polyubiquitination of TRAF6 in intestinal epithelial cells. In contrast, in ASB3-deficient organoids, the integrity of the TRAF6 protein is shielded, consequently decelerating the onset of intestinal inflammation. ASB3 is associated with dysregulation of the colitis microbiota and promotes proinflammatory factors’ production by disrupting TRAF6 stability. Strategies to limit the protein level of ASB3 in intestinal epithelial cells may help in the treatment of colitis.IMPORTANCEUbiquitination is a key process that controls protein stability. We determined the ubiquitination of TRAF6 by ASB3 in intestinal epithelial cells during colonic inflammation. Inflammatory bowel disease patients exhibit upregulated ASB3 expression at focal sites, supporting the involvement of degradation of TRAF6, which promotes TLR-Myd88/TRIF-independent NF-κB aberrant activation and intestinal microbiota imbalance. Sustained inflammatory signaling in intestinal epithelial cells and dysregulated protective probiotic immune responses mediated by ASB3 collectively contribute to the exacerbation of inflammatory bowel disease. These findings provide insights into the pathogenesis of inflammatory bowel disease and suggest a novel mechanism by which ASB3 increases the risk of colitis. Our results suggest that future inhibition of ASB3 in intestinal epithelial cells may be a novel clinical strategy.

Ti and its alloys have been widely applied in various fields of national economy due to their excellent combinations of specific mechanical properties and outstanding corrosion behavior. Among Ti alloys, Ti–1Al–8V–5Fe (Ti-185) alloy is a metastable and low-cost β-Ti alloy, and owns extremely outstanding mechanical performance. In the paper, to overcome the issue of β flecks associated with Fe segregation in conventional ingot metallurgy process, Ti-185 alloy was prepared by electrostatic levitation (ESL) technique at various supercoolings, and its solidification behavior and dendrite growth were systematically analyzed. Moreover, the thermophysical parameters of liquid Ti-185 alloy were tested, and the microstructure, hardness and compressive property were compared to that of cast ingot. Results shown that the maximum supercooling of 311 K in the liquid Ti-185 alloy can be achieved, and a noticeable recalescence phenomenon appears during ESL process. The density and the ratio of specific heat to emissivity of liquid Ti-185 alloy increases linearly with temperature decreasing. Once the crystal nucleus is formed, the nonfacted interface will advance promptly. Moreover, the dendritic growth velocity (v) exhibits an exponential relationship with the supercooling (ΔT), and can be depicted as the equation of v = 1.59·ΔT1.65 mm s−1. Additionally, at a supercooling of 229 K or above, single crystal can be formed using ESL technique. Furthermore, the microhardness, elastic modulus and compressive strength of as-levitated Ti-185 alloy are hardly affected by the supercooling, but the plasticity of as-levitated sample is obviously higher than that of as-cast one.

Rabies, caused by the Rabies virus (RABV), is a highly fatal zoonotic disease. Existing rabies vaccines have demonstrated good immune efficacy, but the complexity of immunization procedures and high cost has impeded the elimination of RABV, particularly in the post-COVID-19 era. There is a pressing need for safer and more effective rabies vaccines that streamline vaccination protocols and reduce expense. To meet this need, we have developed a potential rabies vaccine candidate called ALVAC-RABV-VLP, utilizing CRISPR/Cas9 gene editing technology. This vaccine employs a canarypox virus vector (ALVAC) to generate RABV virus-like particles (VLPs). In mice, a single dose of ALVAC-RABV-VLP effectively activated dendritic cells (DCs), follicular helper T cells (Tfh), and the germinal centre (GC)/plasma cell axis, resulting in durable and effective humoral immune responses. The survival rate of mice challenged with lethal RABV was 100%. Similarly, in dogs and cats, a single immunization with ALVAC-RABV-VLP elicited a stronger and longer-lasting antibody response. ALVAC-RABV-VLP induced superior cellular and humoral immunity in both mice and beagles compared to the commercial inactivated rabies vaccine. In conclusion, ALVAC-RABV-VLP induced robust protective immune responses in mice, dogs and cats, offering a novel, cost-effective, efficient, and promising approach for herd prevention of rabies.

Owing to its ability to provide more accurate and detailed battlefield situational information, fine-grained detection research on soldier targets is of significant importance for military decision-making and firepower threat assessment. To address the issues of low detection accuracy and inaccurate classification in the fine-grained detection of soldier targets, we propose a fine-gain soldier target detection model based on the improved YOLOv8 (You Only Look Once v8). First, we developed a multi-branch feature fusion module to effectively fuse multi-scale feature information and used a dynamic deformable attention mechanism to help the detection model focus on key areas in deep-level features. Second, we proposed a decoupled lightweight dynamic head to extract the position and category information of soldier targets separately, effectively solving the problem of misclassification of soldier targets’ attack actions under different poses. Finally, we used the Inner Minimum Points Distance Intersection over Union (Inner-MPDIoU) to further improve the convergence speed and accuracy of the network model. The proposed improvements are evaluated through comparative experiments conducted in published twenty-six test groups, and the effectiveness of the proposed method is demonstrated. Compared with the original model, our method achieved a detection precision of 78.9%, a 6.91% improvement; the mAP@50 (mean Average Precision at 50) was 79.6%, a 3.51% increase; and an mAP@50-95 of 63.8%, a gain of 5.28%. The proposed method achieves high precision and recall while reducing the computational complexity of the model, thereby enhancing its efficiency and robustness for fine-grained soldier target detection.

In urban warfare and rescue scenarios, the localization of soldiers in staircase environments presents substantial challenges. Addressing this issue, this study introduces the “Target Localization in Staircase Environments-Proximal Policy Optimization” module, which combines object detection with reinforcement learning algorithms. Utilizing a bespoke dataset, “Soldier-Staircase for Tracked Robots”, and design standards tailored for swing-arm tracked robots, the module meets the requirements for autonomous precise localization in staircase environments. A series of experiments conducted in simulated environments verify the module’s efficacy in autonomously and accurately localizing soldier targets in staircase environments, laying the groundwork for further research into the application of reinforcement learning in autonomous robot control.

The importance of the loss function in object detection algorithms based on deep learning has grown significantly technological progress. The accuracy of object detection is significantly affected by bounding box regression, which is a crucial factor. Since the introduction of the Intersection over Union (IoU) loss in 2016, many improvements have been proposed based on this loss function. These studies considered various geometric factors related to bounding boxes, and constructed penalty terms to address this issue. This paper summarizes these functions and introduces a new Fused IoU (FIoU) loss function that leads to superior performance. The FIoU loss function not only solves the problem of gradient vanishing during the backpropagation process of the IoU loss function but also solves the problem of some IoU-based loss functions degenerating into IoU loss functions under certain conditions. In addition, in the simulation experiments, the FIoU loss function resulted in faster convergence speed. In our ablation experiments across different datasets and algorithms, our aim was to compare the mAP metrics under different loss functions. On the test set of the Pascal VOC dataset, employing the Faster R-CNN algorithm, FIoU demonstrated improvements of 1.1% and 1.7% over GIoU and Smooth $\ell _{1}$ , respectively. With the YOLOX algorithm, FIoU outperformed GIoU and IoU by 1.0% and 0.8%. Utilizing the YOLOv7 algorithm, we evaluated seven loss functions, achieving optimal results with FIoU. On the validation set of the MS-COCO 2017 dataset, using YOLOv7 and YOLOv8, FIoU exhibited gains of 0.4%, 0.2%, 0.2% over EIoU, DIoU, GIoU, and 0.3%, 0.5%, 0.3% over EIoU, DIoU, GIoU, respectively.

Abstract Vaccination is still the most promising strategy for combating influenza virus pandemics. However, the highly variable characteristics of influenza virus make it difficult to develop antibody-based universal vaccines, until now. Lung tissue-resident memory T cells (TRM), which actively survey tissues for signs of infection and react rapidly to eliminate infected cells without the need for a systemic immune reaction, have recently drawn increasing attention towards the development of a universal influenza vaccine. We previously designed a sequential immunization strategy based on orally administered Salmonella vectored vaccine candidates. To further improve our vaccine design, in this study, we used two different dendritic cell (DC)-targeting strategies, including a single chain variable fragment (scFv) targeting the surface marker DC-CD11c and DC targeting peptide 3 (DCpep3). Oral immunization with Salmonella harboring plasmid pYL230 (S230), which displayed scFv-CD11c on the bacterial surface, induced dramatic production of spleen effector memory T cells (TEM). On the other hand, intranasal boost immunization using purified DCpep3-decorated 3M2e-ferritin nanoparticles in mice orally immunized twice with S230 (S230inDC) significantly stimulated the differentiation of lung CD11b+ DCs, increased intracellular IL-17 production in lung CD4+ T cells and elevated chemokine production in lung sections, such as CXCL13 and CXCL15, as determined by RNAseq and qRT‒PCR assays, resulting in significantly increased percentages of lung TRMs, which could provide efficient protection against influenza virus challenge. The dual DC targeting strategy, together with the sequential immunization approach described in this study, provides us with a novel “prime and pull” strategy for addressing the production of protective TRM cells in vaccine design.

Abstract Surgical site infections (SSI) are major post‐operative complications following surgery. Reducing SSI is a global urgency as they account for huge pecuniary, physiological, and emotional burdens for patients. Antibiotic resistance is the main challenge for surgeons dealing with SSIs. Aggregation‐induced emission photosensitisers (AIE PS) with their distinct optical characteristics, biocompatibility, low toxicity, and target specificity, hold the potential for the treatment of SSI. Herein, a synergetic strategy combining plasma polymerization and AIE PS is adopted to develop coatings that can eradicate SSI‐causing bacteria. These coatings can preferentially kill Gram‐negative and Gram‐positive bacteria over mammalian cells after triggered by light irradiation. The cell viability and immunostaining studies confirmed their biocompatibility on mammalian cells. The antibacterial mechanistic studies explored their ability to generate reactive oxygen species (ROS), which is crucial for overcoming antibiotic resistance. Thus, this study opens an avenue toward antibacterial coatings to decrease the prevalence of SSI.

ABSTRACTCanine distemper virus (CDV) poses a severe threat to both domesticated and wild animals, including multiple carnivores. With the continued expansion of its host range, there is an urgent need for the development of a safer and more effective vaccine. In this study, we developed subunit vaccines based on a bacterium-like particle (BLP) delivery platform containing BLPs-F and BLPs-H, which display the CDV F and H glycoprotein antigens, respectively, using the antigen-protein anchor fusions produced by a recombinant baculovirus insect cell expression system. The combination of BLPs-F and BLPs-H (CDV-BLPs), formulated with colloidal manganese salt [Mn jelly (MnJ)] adjuvant, triggered robust CDV-specific antibody responses and a substantial increase in the number of interferon gamma (IFN-γ)-secreting CD4+ and CD8+ T cells in mice. Dogs immunized intramuscularly with this vaccine not only produced CDV-specific IgG but also displayed elevated concentrations of IFN-γ and interleukin 6 in their serum, along with an increase of the CD3+CD4+ and CD3+CD8+ T cell subsets. Consequently, this heightened immune response provided effective protection against disease development and reduced viral shedding levels following challenge with a virulent strain. These findings suggest that this BLP-based subunit vaccine has the potential to become a novel canine distemper vaccine.IMPORTANCEMany sensitive species require a safe and effective distemper vaccine. Non-replicating vaccines are preferred. We constructed subunit particles displaying canine distemper virus (CDV) antigens based on a bacterium-like particle (BLP) delivery platform. The CDV-BLPs formulated with theMn jelly adjuvant induced robust humoral and cell-mediated immune responses to CDV in mice and dogs, thereby providing effective protection against a virulent virus challenge. This work is an important step in developing a CDV subunit vaccine.

ABSTRACTArbuscular mycorrhizal fungi (AMF) could establish symbiosis with plant roots, which enhances plant resistance to various stresses, including drought stress and salt stress. Besides AMF, chemical stimulants such as trehalose (Tre) can also play an important role in helping plants alleviate damage of adversity. However, the mechanism of the effect of AMF combined with chemicals on plant stress resistance is unclear. The objective of this study was to explore the synergistic effects of Claroideoglomus etunicatum AMF and exogenous Tre on the antioxidant system, osmoregulation, and resistance-protective substance in plants in response to salt stress. Tomato seedlings were inoculated with Claroideoglomus etunicatum and combined with exogenous Tre in a greenhouse aseptic soil cultivation experiment. We measured the arbuscular mycorrhizal symbiont development, organic matter content, and antioxidant enzyme activity in tomato seedlings. Both AMF and Tre improved the synthesis of chlorophyll content in tomato seedlings; regulated the osmotic substance including soluble sugars, soluble protein, and proline of plants; and increased the activity of superoxide dismutase, peroxidase, and catalase. The combination of AMF and Tre also reduced the accumulation of malondialdehyde and alleviated the damage of harmful substances to plant cells in tomato seedlings. We studied the effects of AMF combined with extraneous Tre on salt tolerance in tomato seedlings, and the results showed that the synergistic treatment of AMF and Tre was more efficient than the effects of AMF inoculation or Tre spraying separately by regulating host substance synthesis, osmosis, and antioxidant enzymes. Our results indicated that the synergistic effects of AMF and Tre increased the plant adaptability against salt damage by enhancing cell osmotic protection and cell antioxidant capacity.IMPORTANCEAMF improve the plant adaptability to salt resistance by increasing mineral absorption and reducing the damage of saline soil. Trehalose plays an important role in plant response to salt damage by regulating osmotic pressure. Together, the use of AMF and trehalose in tomato seedlings proved efficient in regulating host substance synthesis, osmosis, and antioxidant enzymes. These synergistic effects significantly improved seedling adaptability to salt stress by enhancing cell osmotic protection and cell antioxidant capacity, ultimately reducing losses to crops grown on land where salinization has occurred.

CO2 capture and storage technology is favorable for the reduction of CO2 emissions. In recent years, a great number of research achievements have been obtained on CO2 geological storage from nano scale to oil/gas reservoir scale, but most studies only focus on the flow behaviors in single-dimension porous media. Besides, the physical experiment method is influenced by many uncertain factors and consumes a lot of time and cost. In order to deeply understand the flow behaviors in the process of CO2 geological storage in microscopic view and increase the volume of CO2 geological storage, this paper established 2D and 3D models by using VOF (Volume of Fluid) method which can track the dynamic change of two-phase interface, to numerically simulate supercritical CO2-brine two-phase flow. Then, the distribution characteristics of CO2 clusters and the variation laws of CO2 saturation under different wettability, capillary number and viscosity ratio conditions were compared, and the intrinsic mechanisms of CO2 storage at pore scale were revealed. And the following research results were obtained. First, with the increase of rock wettability to CO2, the sweep range of CO2 enlarged, and the disconnection frequency of CO2 clusters deceased, and thus the volume of CO2 storage increased. Second, with the increase of capillary number, the displacement mode transformed from capillary fingering to stable displacement, and thus the volume of CO2 storage increased. Third, as the viscosity of injected supercritical CO2 gradually approached that of brine, the flow resistance between two-phase fluids decreased, promoting the ''lubricating effect''. As a result, the flow capacity of CO2 phase was improved, and thus the volume of CO2 storage was increased. Fourth, the influence degrees of wettability, capillary number and viscosity ratio on CO2 saturation were different in multi-dimensional porous media models. In conclusion, the CO2-brine two-phase flow simulation based on VOF method revealed the flow mechanisms in the process of CO2 geological storage at pore scale, which is of guiding significance to the development of CCUS technology and provides theoretical guidance and technical support for the study of CO2 geological storage in a larger scale.

Abstract Objective To analyze the motion characteristics of lumbar facet joints and to observe the effect of weight-bearing on lumbar facet joints in the sitting position. Methods Ten normal subjects (5 males and 5 females) were recruited and scanned by CT, and their lumbar 3D models were reconstructed by software. The images of flexion and extension of lumbar facet joints in the sitting position were collected without weight-bearing and weight-bearing 10 kg, and the 2D model was constructed by software. The 2D-3D model was matched to restore the flexion and extension motion changes of the subjects’ lumbar spine in the sitting position. Coordinates were established in the middle of the vertebral body and copied to the facet joints. Measure and record the lumbar facet joint movement distance through coordinate system. The relevant data of facet joints were collected. Results In the L3/4 segment, after weight loading, the displacement of the left facet joint in the X axis became larger, while that in the Y axis and Z axis decreased. The displacement of the right facet joint in the X axis and Y axis increased, and the Z axis displacement decreased. The rotation angle of the bilateral facet joints also decreased. In the L4/5 segment, after loading, the displacements of the X, Y, and Z axis displacements of both sides increase, while the rotation angles of α and β increase, while the rotation angle of γ decreases. In the L5/S1 segment, the displacements of the X, Y, and Z axes on the left side decrease. The displacement of the X and Y axes on the right side decreases, while the displacement on the Z axis increases. The rotation angles of α and γ increase, and the rotation angle of the β axis decreases. Conclusion When sitting, the flexion and extension distance and rotational displacement of lumbar facet joints are not affected by weight-bearing. In addition, there is asymmetry in the movement of the left and right facet joints, and weight bearing has no effect on the asymmetry of the motion.

Doxorubicin, a potent chemotherapeutic agent used extensively in cancer treatment, displays complex pharmacokinetic behavior, especially across various formulations. With a rising incidence of cancer cases in cats, understanding the drug’s pharmacokinetics in feline subjects remains a critical yet unexplored area. Hence, this study investigated the pharmacokinetic profile of doxorubicin after slow intravenous administration of doxorubicin hydrochloride (DOX·HCl) or doxorubicin hydrochloride pegylated liposome (DOX·HCl-PLI) in twelve cats at a single dose of 20 mg/m2. Blood samples collected at pretreatment time (0 h) and over 192 h were analyzed using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). The obtained pharmacokinetic parameters of doxorubicin revealed significant differences between the two formulations and were as follows: elimination half-life (T1/2λz) of 5.00 ± 3.20 h (DOX·HCl) and 17.62 ± 8.13 h (DOX·HCl-PLI), area under the concentration/time curve from 0 to last point (AUClast) of 0.67 ± 0.12 μg hr./mL (DOX·HCl) and 783.09 ± 267.29 μg hr./mL (DOX·HCl-PLI), and total body clearance (CL_obs) of 27098.58 ± 5205.19 mL/h/m2 (DOX·HCl) and 28.65 ± 11.09 mL/h/m2 (DOX·HCl-PLI). Additionally, differences were also detected in the apparent volume of distribution (Vz_obs) with 178.56 ± 71.89 L/m2 (DOX·HCl) and 0.64 ± 0.20 L/m2 (DOX·HCl-PLI), and the maximum plasma concentration (Cmax) with 2.25 ± 0.30 μg/mL (DOX·HCl) and 24.02 ± 5.45 μg/mL (DOX·HCl-PLI). Notably, low concentration of doxorubicinol, the metabolite of doxorubicin, was detected in plasma after administration of DOX·HCl, with even less present when DOX·HCl-PLI was administered. This investigation provides valuable insights into the distinct pharmacokinetic behaviors of DOX·HCl and DOX·HCl-PLI in cats, contributing essential groundwork for future studies and potential clinical applications in feline oncology.

Eucalyptus pellita has the characteristics of rapid growth and high resistance. However, there is little research on molecular breeding of E. pellita, which is essential to shortening breeding life and selecting quality varieties. Therefore, a crucial step before selective breeding can be carried out to increase the wood quality of E. pellita is identifying genetic diversity and population structure using single nucleotide polymorphism (SNP) markers. In this study, the genetic diversity of 1st generation 196 E. pellita families from 23 geographically defined was assessed using 1,677,732 SNP markers identified by whole genome resequencing. SNP annotation showed that the ratio of non-synonymous to synonymous coding mutations was 0.83. Principal component analysis (PCA), phylogenetic tree, and population structure analysis permitted the families to be categorized into three groups, one of which (G2) contains most of the Indonesian (IDN) and Papua New Guinea (PNG) families. Genetic relationship analysis showed that IDN was closely related to PNG. Genetic diversity analysis showed that He, PIC, I, and H mean values were 0.2502, 0.2027, 0.3815, and 0.2680, respectively. PCA analysis classified various provenances in QLD into two categories (G1 and G3). The genetic diversity of G3 was higher than that of G2. The results of genetic differentiation (Fst) showed that PNG region was divided into two groups (PNG1 and PNG2), the Fst (0.172) between QLD and PNG2 region was higher than QLD and PNG1, and the Fst (0.024) between IDN and PNG1 is smaller than IDN and PNG2. A Mantel test revealed a positive correlation between the genetic and geographic distance of E. pellita. This study has a certain reference value for genetic identification, germplasm preservation, and breeding of E. pellita. Also, it provides a basis for subsequent association analysis to explore excellent alleles and introduction.

Background: Cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) is an immunosuppressive checkpoint that is involved in the development and metastasis of cancers. Several studies revealed that CTLA-4 rs231775A/G polymorphism may be associated with the risk of cancer in some populations, but the conclusions of these studies are not consistent. Methods: We conducted a pooled analysis with eligible studies to explore the association between the CTLA-4 rs231775 variant and cancer risk. Additionally, we used in silico tools to evaluated the expression of CTLA-4 on urinary system cancer. Moreover, we adopted the enzyme-linked immunosorbent assay (ELISA), and Gene Set Enrichment Analysis (GSEA) to investigate the effects of CTLA-4 on bladder cancer (BLCA). Results: In total, 92 case-control studies involving 29,987 patients with cancer and 36,484 healthy individuals (controls) were included in the pooled analysis. In the stratified analysis based on cancer type, the rs231775 A/G polymorphism was associated with increased bladder cancer risk in the heterozygote contrast model (OR = 1.23, 95% CI = 1.01–1.51, P = 0.040). The race-stratified analysis revealed that East Asians with the GG genotype had a 12% lower risk of developing cancer than those with the GA + AA genotype (95% CI = 0.81–0.95, P = 0.001). The in silico analysis showed that CTLA-4 expression was augmented in patients with BLCA. The ELISA results revealed that CTLA-4 expression was reduced in patients with BLCA carrying the AA genotype. Several signaling pathways, including cytokine-cytokine receptor interactions and T-cell receptor signaling, were associated with CTLA-4 expression. Conclusion: The CTLA-4 rs231775 A/G polymorphism is associated with cancer risk in East Asian population. This polymorphism is especially associated with BLCA.

Abstract Epidemiological studies have confirmed salt sensitivity as a crucial risk factor for the development of hypertension. However, few studies have investigated the association between salt sensitivity of blood pressure (SSBP) and hypertension in Chinese Tibetan population. Therefore, we conducted a cross‐sectional study based on a Tibetan population to evaluate the association between SSBP and the risk of hypertension. Seven hundred and eighty‐four participants with hypertension and 645 participants without hypertension were included from five villages in Tibetan Autonomous Region of Gannan during 2013–2014. The assessment of salt sensitivity (SS) and non‐salt sensitivity (NSS) was performed according to mean arterial pressure (MAP) changes by the modified Sullivan's acute oral saline load and diuresis shrinkage test (MSAOSL‐DST). Logistic regression models and restricted cubic models were used to examine the association between SSBP and hypertension. There were 554 (70.5%) salt‐sensitive participants with hypertension and 412 (63.9%) salt‐sensitive participants without hypertension in this study. Compared with individuals with NSS, individuals with SS had a significantly increased risk of hypertension, and the multiple‐adjusted odds ratios were 2.582 with 95% confidence interval of 1.357–4.912. Furthermore, a significant linear trend was found between MAP changes and hypertension. Subgroup analyses showed significant and stronger associations between SSBP and the risk of hypertension in the older (age ≥ 55 years old), males and participants who took exercise less than 1 time per week. Our results suggest that SS is associated with an increased risk of hypertension in Tibetan population, indicating a need for clinicians dealing with SSBP to decrease the risk of hypertension.

In the process of geothermal tailwater reinjection of sandstone, the problem of plugging has been seriously restricting the continuous development of geothermal reinjection for many years, and the problems of plugging are complex and changeable. The plugging in the process of reinjection can be divided into physical plugging, chemical plugging, microbial plugging and gas plugging. Given these four types of blocking, according to the mechanism characteristics of the blocking caused by them, this paper puts forward corresponding blocking prevention measures and solves the current blocking problems by filtering, adding a scale inhibitor, intermittent reinjection, adding chlorine dioxide and regular lifting. In addition, the existing reinjection process and the equipment flow are relatively simple and cannot achieve the goal of efficient reinjection. Therefore, a complete set of reinjection processes is designed to ensure the efficient reinjection of sandstone geothermal tailwater. HIGHLIGHT Through theoretical analysis and simulation experiments, the prevention and control measures for various types of plugging are proposed, which lay a theoretical foundation for the high efficiency of geothermal tailwater.; The innovation lies in the design of a set of the special process flow for the geothermal reinjection of sandstone.;

Canine distemper virus (CDV) can cause fatal infections in giant pandas. Vaccination is crucial to prevent CDV infection in giant pandas. In this study, two bacterium-like particle vaccines F3-GEM and H4-GEM displaying the trimeric F protein or tetrameric H protein of CDV were constructed based on the Gram-positive enhanced-matrix protein anchor (GEM-PA) surface display system. Electron microscopy and Western blot results revealed that the F or H protein was successfully anchored on the surface of GEM particles. Furthermore, one more bacterium-like particle vaccine F3 and H4-GEM was also designed, a mixture consisting of F3-GEM and H4-GEM at a ratio of 1:1. To evaluate the effect of the three vaccines, mice were immunized with F3-GEM, H4-GEM or F3 and H4-GEM. It was found that the level of IgG-specific antibodies and neutralizing antibodies in the F3 and H4-GEM group was higher than the other two groups. Additionally, F3 and H4-GEM also increased the secretion of Th1-related and Th2-related cytokines. Moreover, F3 and H4-GEM induce IgG and neutralizing antibodies’ response in dogs. Conclusions: In summary, F3 and H4-GEM can provoke better immune responses to CDV in mice and dogs. The bacterium-like particle vaccine F3 and H4-GEM might be a potential vaccine candidate for giant pandas against CDV infection.

There is growing concern regarding cadmium (Cd) exposure through rice consumption. Compared with alternate wetting and drying (AWD), continuous flooding (CF) is usually considered as an effective approach for reducing Cd enrichment in rice but increases the risk of pollution from arsenic (As). In this study, the field trial was conducted to investigate remediation effects of two water management (CF and AWD) techniques on Cd pollution in rice in typical japonica rice cultivation areas with varied soil pH levels. The results indicate that soil pH was a crucial factor in regulating CF-mediated Cd/As accumulation and migration in rice plants, and grains at all stages of rice growth. In acidic fields, compared with AWD, the use of CF reduced the accumulation of Cd in plants during the tillering stage; CF during the milk stage promotes the risk of contamination of Cd in rice grains and any form of As in plants and inhibits the content of any forms of As in grains. During the mature stage, CF reduced the levels of Cd in the plants and grains while promoting the accumulation of As(V) and total As(T-As) in plants and As(III) in grains. In alkaline fields, compared with AWD, CF during the tillering stage promoted the accumulation of various forms of As in plants. During the milk stage, CF increased and decreased the Cd content in plants and grains, respectively, and reduced the accumulation of T-As in plants and As(III) in grains; during the mature stage, CF promoted the accumulation of Cd in plants and grains, induced the accumulation of T-As plants, and inhibited the accumulation of any form of As in grains. From the perspective of food safety, the impact of CF conditions on the accumulation of Cd and As in rice from acidic fields exhibited a pattern of reduction in Cd and increase in As during the maturity period, as compared to that on the AWD. Conversely, CF increased the Cd risk while simultaneously reducing the As accumulation in rice grains to a safe level in alkaline fields. CF is not recommended as a remediation strategy for Cd pollution in rice in low Cd pollution areas, but it can be considered as a potential strategy for As pollution remediation in rice in alkaline fields with low Cd pollution.

In the quest to curtail the spread of healthcare-associated infections, this work showcases the fabrication of a cutting-edge antibacterial textile coating armoured with aggregation-induced emission photosensitisers (AIE PS) to prevent bacterial colonisation on textiles. The adopted methodology includes a multi-step process using plasma polymerisation and subsequent integration of AIE PS on their surface. The antibacterial effectiveness of the coating was tested against Pseudomonas aeruginosa and Staphylococcus aureus after light irradiation for 1 h. Furthermore, antibacterial mechanistic studies revealed their ability to generate reactive oxygen species that can damage bacterial cell membrane integrity. The results of this investigation can be used to develop ground-breaking explanations for infection deterrence, principally in situations where hospital fabrics play a critical part in the transmission of diseases. The antibacterial coating for textiles developed in this study holds great promise as an efficient strategy to promote public health and reduce the danger of bacterial diseases through regular contact with fabrics.

SYAUP-491 is a novel alkyl sulfonamide. In this study, in vivo and in vitro tests were performed along with a proteomic analysis to determine the effects and underlying mechanisms of the antibacterial activity of SYAUP-491 against the causative agent of bacterial leaf blight in rice. The antibacterial test results suggested that SYAUP-491 exhibited significant activities against Xanthomonas oryzae pv. oryzae (Xoo) in vitro and in vivo. The minimal EC50 values reached 6.96 μg/mL and the curative activity reached 74.1%. Detailed studies demonstrated that SYAUP-491 altered membrane permeability and caused morphological changes. Based on proteomics results, SYAUP-491 might inhibit bacterial protein synthesis. SYAUP-491 may disrupt and alter cell membrane permeability and could further act on ribosomes in the bacterial body. Given the above results, SYAUP-491 could serve as a new lead compound in the research of antibacterial control of plant pathogenic bacterial disease.

An important part of geothermal development is the re-injection of waste geothermal fluids into the reservoir, which can extend the life of the geothermal resource. However, the difficulty of recharge and the clogging problem in the recharge process are still a worldwide problem that restricts the sustainable development and utilization of sandstone geothermal reservoirs. The main factor affecting the recharge effect is physical clogging. In this paper, a series of simulation experiments were conducted to study the physical clogging in the recharge process of sandstone thermal storage in the Lubei area, which conclude that the degree of clogging is related to the particle size and concentration of suspended matter. At a certain particle size, the clogging is most serious when the experimental suspended matter concentration gradient is up to 140 mg/L. In addition, particle migration in clogging is related to the recharge flow rate, and the critical flow rate is 0.75–2 mL/min, which is experimentally derived, and it is recommended that the recharge rate should be controlled below 0.75 mL/min during the actual recharge. This paper provides a scientific basis for the efficient recharge of geothermal tailwater through the study of the clogging mechanism. HIGHLIGHTS The mechanism of action of sandstone thermal storage recharge blockage is studied by theoretical analysis and simulation experiments.; The action process of suspension blockage and the mechanical characteristics of particle transport were studied.; A variation law of clogging is experimentally derived.; A solid foundation is laid for the efficient recharge of sandstone thermal storage.;

Abstract Objective To analyse and compare the biomechanical differences between 3D-printed prostheses, titanium mesh cages and poorly matched titanium mesh cages in total en bloc spondylectomy (TES). Methods The finite element model of T10-L2 for healthy adults was modified to make three models after T12 total spondylectomy. These models were a 3D-printed prosthesis, titanium mesh cage and prosthesis-endplate mismatched titanium mesh cage for reconstruction. The range of motion (ROM), stress distribution of the endplate and internal fixation system of three models in flexion and extension, lateral bending and axial rotation were simulated and analysed by ABAQUS. Result In flexion, due to the support of the anterior prosthesis, the fixation system showed the maximum fixation strength. The fixation strength of the 3D-printed prosthesis model was 26.73 N·m /°, that of the TMC support model was 27.20 N·m /°, and that of the poorly matched TMC model was 24.16 N·m /°. In flexion, the L1 upper endplate stress of the poorly matched TMC model was 35.5% and 49.6% higher than that of the TMC and 3D-printed prosthesis, respectively. It was 17% and 28.1% higher in extension, 39.3% and 42.5% higher in lateral bending, and 82.9% and 91.2% higher in axial rotation, respectively. The lower endplate of T11 showed a similar trend, but the magnitude of the stress change was reduced. In the stress analysis of the 3D-printed prosthesis and TMC, it was found that the maximum stress was in flexion and axial rotation, followed by left and right bending, and the least stress was in extension. However, the mismatched TMC withstood the maximum von Mises stress of 418.7 MPa (almost twice as much as the buckling state) in rotation, 3 times and 5.83 times in extension, and 1.29 and 2.85 times in lateral bending, respectively. Conclusion Different prostheses with good endplate matching after total spondylectomy can obtain effective postoperative stable support, and the reduction in contact area caused by mismatch will affect the biomechanical properties and increase the probability of internal fixation failure.

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) in foods has been associated with severe infections in humans and animals worldwide. In the present study, the molecular characteristics of livestock-associated MRSA (LA-MRSA) and human-associated MRSA (hMRSA) isolates obtained in China, as well as MRSA isolates obtained from raw milk in 2018, were investigated. In total, 343 (20.38%; 343/1,683) S. aureus isolates were obtained from 1,683 raw milk samples from 100 dairy farms in 11 provinces across China. Among these, 49 (2.91%; 49/1,683) were mecA-positive MRSA. All LA-MRSA isolates were resistant to penicillin and highly resistant to erythromycin, sulfisoxazole, and clindamycin. Bioinformatic analysis the 49 genomes of LA-MRSA and 71 previously published hMRSA genomes isolated from Chinese individuals in 2018 indicated that blaZ, erm, ant(6)-Ia, aph(3′)-III, tet(K), cat, and aph(2″)-Ia were more prevalent in MRSA from raw milk (P

ABSTRACT The influenza virus continues to pose a great threat to public health due to the frequent variations in RNA viruses. Vaccines targeting conserved epitopes, such as the extracellular domain of the transmembrane protein M2 (M2e), a nucleoprotein, and the stem region of hemagglutinin proteins, have been developed, but more efficient strategies, such as nanoparticle-based vaccines, are still urgently needed. However, the labor-intensive in vitro purification of nanoparticles is still necessary, which could hinder the application of nanoparticles in the veterinary field in the future. To overcome this limitation, we used regulated lysis Salmonella as an oral vector with which to deliver three copies of M2e (3M2e-H1N1)-ferritin nanoparticles in situ and evaluated the immune response. Then, sequential immunization using Salmonella-delivered nanoparticles followed by an intranasal boost with purified nanoparticles was performed to further improve the efficiency. Compared with 3M2e monomer administration, Salmonella-delivered in situ nanoparticles significantly increased the cellular immune response. Additionally, the results of sequential immunization showed that the intranasal boost with purified nanoparticles dramatically stimulated the activation of lung CD11b dendritic cells (DCs) and elevated the levels of effector memory T (TEM) cells in both spleen and lung tissues as well as those of CD4 and CD8 tissue-resident memory T (TRM) cells in the lungs. The increased production of mucosal IgG and IgA antibody titers was also observed, resulting in further improvements to protection against a virus challenge, compared with the pure oral immunization group. Salmonella-delivered in situ nanoparticles efficiently increased the cellular immune response, compared with the monomer, and sequential immunization further improved the systemic immune response, as shown by the activation of DCs, the production of TEM cells and TRM cells, and the mucosal immune response, thereby providing us with a novel strategy by which to apply nanoparticle-based vaccines in the future. IMPORTANCE Salmonella-delivered in situ nanoparticle platforms may provide novel nanoparticle vaccines for oral administration, which would be beneficial for veterinary applications. The combination of administering Salmonella-vectored, self-assembled nanoparticles and an intranasal boost with purified nanoparticles significantly increased the production of effector memory T cells and lung resident memory T cells, thereby providing partial protection against an influenza virus challenge. This novel strategy could open a novel avenue for the application of nanoparticle vaccines for veterinary purposes.

Abstract African swine fever virus (ASFV) is an important pathogen causing acute infectious disease in domestic pigs and wild boars that seriously endangers the global swine industry. As ASFV is structurally complex and encodes a large number of functional proteins, no effective vaccine has been developed to date. Thus, dissecting the mechanisms of immune escape induced by ASFV proteins is crucial. A previous study showed that the ASFV-encoded protein is an important factor in host immunity. In this study, we identified a negative regulator, MGF505-3R, that significantly downregulated cGAS/STING- and poly (dG:dC)-mediated IFN-β and interferon stimulation response element (ISRE) reporter activity and suppressed IFNB1 and IFIT2 mRNA levels. In addition, TBK1, IRF3 and IκBα phosphorylation levels were also inhibited. Mechanistically, MGF505-3R interacted with cGAS/TBK1/IRF3 and targeted TBK1 for degradation, thereby disrupting the cGAS-STING-mediated IFN-β signaling pathway, which appears to be highly correlated with autophagy. Knockdown MGF505-3R expression enhanced IFN-β and IL-1β production. Taken together, our study revealed a negative regulatory mechanism involving the MGF505-3R-cGAS-STING axis and provided insights into an evasion strategy employed by ASFV that involves autophagy and innate signaling pathways.

Summary: Porcine reproductive and respiratory syndrome (PRRS) is an epidemic animal infectious disease worldwide. In our previous research it was suggested that matrine could inhibit PRRSV infection both in vitro and in vivo, but the antiviral mechanisms are still undecided. Network pharmacology can well solve the difficult problem of “multiple targets, multiple pathways” in the research of TCM action targets. The results of network pharmacology indicated that matrine exerts its anti-PRRSV effect by targeting HSPA8 and HSP90AB1. The results of real-time fluorescent quantitative PCR and western blot showed that infection with PRRSV induced a significant increase in the expression of HSPA8 and HSP90AB1 whereas matrine treatment could significantly reverse it, and the number of viruses of PRRSV also decreased. In this study, the method of network pharmacology was used to explore HSPA8 and HSP90AB1 which were the potential targets of matrine against PRRSV on Marc-145 cells.

Abstract Background Buserelin is a luteinizing hormone releasing hormone (LHRH) agonist used for the treatment of hormone-dependent diseases in males and females. However, the pharmacokinetics of buserelin in pigs and cows are not fully understood. This study was designed to develop a sensitive method to determine the concentration of buserelin in blood plasma and to investigate the pharmacokinetic parameters after intramuscular (i.m.) administration in pigs and cows. Results A sensitive and rapid stability method based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed. The pharmacokinetic parameters of buserelin after i.m. administration were studied in five pigs and five cows at a single dose of 1 mg per pig and 3 mg per cow. The plasma kinetics were analyzed by WinNonlin 8.1.0 software using a non-compartmental model. The mean concentration area under the curve (AUC0-t) was 25.02 ± 6.93 h × ng/mL for pigs and 5.63 ± 1.86 h × ng/mL for cows. The maximum plasma concentration (Cmax) and time to reach the maximum concentration (tmax) were 10.99 ± 2.04 ng/mL and 0.57 ± 0.18 h for pigs and 2.68 ± 0.36 ng/mL and 1.05 ± 0.27 h for cows, respectively. The apparent volume of distribution (Vz) in pigs and cows was 80.49 ± 43.88 L and 839.88 ± 174.77 L, respectively. The elimination half-time (t1/2), and clearance (CL) were 1.29 ± 0.40 h and 41.15 ± 11.18 L/h for pigs and 1.13 ± 0.3 h and 545.04 ± 166.40 L/h for cows, respectively. No adverse effects were observed in any of the animals. Conclusion This study extends previous studies describing the pharmacokinetics of buserelin following i.m. administration in pigs and cows. Further studies investigating other factors were needed to establish therapeutic protocol in pigs and cows and to extrapolate these parameters to others economic animals.

Abstract The type I interferon (IFN-I) signaling pathway is an important part of the innate immune response and plays a vital role in controlling and eliminating pathogens. African swine fever virus (ASFV) encodes various proteins to evade the host’s natural immunity. However, the molecular mechanism by which the ASFV-encoded proteins inhibit interferon production remains poorly understood. In the present study, ASFV MGF360-11L inhibited cGAS, STING, TBK1, IKKε, IRF7 and IRF3-5D mediated activation of the IFN-β and ISRE promoters, accompanied by decreases in IFN-β, ISG15 and ISG56 mRNA expression. ASFV MGF360-11L interacted with TBK1 and IRF7, degrading TBK1 and IRF7 through the cysteine, ubiquitin–proteasome and autophagy pathways. Moreover, ASFV MGF360-11L also inhibited the phosphorylation of TBK1 and IRF3 stimulated by cGAS-STING overexpression. Truncation mutation analysis revealed that aa 167-353 of ASFV MGF360-11L could inhibit cGAS-STING-mediated activation of the IFN-β and ISRE promoters. Finally, the results indicated that ASFV MGF360-11L plays a significant role in inhibiting IL-1β, IL-6 and IFN-β production in PAM cells (PAMs) infected with ASFV. In short, these results demonstrated that ASFV MGF360-11L was involved in regulating IFN-I expression by negatively regulating the cGAS signaling pathway. In summary, this study preliminarily clarified the molecular mechanism by which the ASFV MGF360-11L protein antagonizes IFN-I-mediated antiviral activity, which will help to provide new strategies for the treatment and prevention of ASF.

Military target detection technology is the foundation and key to perceive and analyze the battlefield situation, and it is also the premise of target tracking technology. Aiming at the task of military target detection, the detection performance of traditional detection algorithms is poor in complex environment. We realized automatic detection of military targets in complex environment through deep learning. In this research, we improved the components of YOLOv3 and proposed a novel military target detection algorithm (YOLO-G). We have built a military target dataset composed of armed men with different weapons, which provides a test environment for various object detection algorithms. In the YOLOv3 network structure, by introducing the lightweight convolutional neural network GhostNet as the feature extraction network, the accuracy and speed of military target detection are improved. Then, the attention mechanism based on the coordinate attention block is introduced to enhance the representation ability of target features, suppress interference and improve the detection accuracy. Finally, the loss function of the target detector is redesigned by using DIOU loss function and Focal loss function, which further improves the detection accuracy of our detection model for military targets. We tested YOLO-G on the military target dataset. Experimental results show that our method improves the mAP by 2.9% and the detection speed by 25.9 frames/s compared with the original YOLOv3 algorithm, and the size of the proposed model is reduced to 1/6 of that of YOLOv3. In addition, we also compared our method with several state-of-the-art object detection algorithms. The results show that YOLO-G also has superior detection performance, and the mAP index obtained by our method is 1.2% higher than that of the latest YOLOv5 on the premise of meeting the application requirements. The improved network model can provide effective auxiliary technical support for battlefield situation generation and analysis.

Osteoarthritis (OA) causes joint pain, stiffness, and dysfunction in middle-aged and older adults; however, its pathogenesis remains unclear. Circular RNAs (circRNAs) are differentially expressed in patients with OA and participate in a multigene, multitarget regulatory network. CircRNAs are involved in the development of OA through inflammatory responses, including proliferation, apoptosis, autophagy, differentiation, oxidative stress, and mechanical stress. Most circRNAs are used as intracellular miRNA sponges in chondrocytes, endplate chondrocytes, mesenchymal stem cells, synoviocytes, and macrophages to promote the progression of OA. However, a small portion of circRNAs participates in the pathogenesis of OA by intracellular mechanisms, such as protein binding, methylation, or intercellular exosome pathways. In this sense, circRNAs might serve as potential novel biomarkers and therapeutic targets for OA.

Abstract Introduction Steroid-induced osteonecrosis of the femoral head (ONFH) is a disease of the bone. Metabolism and genetic factors are generally considered to play an important role. The purpose of this study was to investigate the relationship between single-nucleotide polymorphisms (SNPs) in MIR17HG and MIR155HG and the risk of steroid-induced ONFH in the population of northern China. Methods A total of 199 steroid-induced ONFH patients and 506 healthy controls were recruited for the study. Four SNPs of MIR17HG and seven SNPs of MIR155HG were genotyped by Sequenom MassARRAY. ORs and 95% CIs were used to evaluate the relationship between these SNPs and steroid-induced ONFH. Results In the codominant model, patients with the MIR17HG SNPs (rs7318578) AA genotype had an increased risk of steroid-induced ONFH (OR = 1.79, p = 0.039); in the recessive model, patients with the MIR17HG SNP (rs7318578) AA genotype had an increased risk of steroid-induced ONFH (OR = 1.78, p = 0.032). Stratified analysis showed that a MIR17HG SNP (rs7318578) and the MIR155HG SNPs (rs77218221, rs11911469, rs34904192 and rs4143370) were closely related to different unornamented phenotypes of steroid-induced ONFH. Analysis of the clinical indicators revealed significant differences in high-density lipoprotein (HDL-C) levels between the ONFH group and the control group (p = 0.005). In the MIR17HG SNP (rs75267932), patients with different genotypes had different levels of triglyceride (TG). The MIR155HG SNPs (rs77699734, rs1893650, and rs34904192) showed differences in triglyceride (TG), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) levels in patients with different genotypes. Conclusion Our results confirm that MIR17HG and MIR155HG gene mutations are associated with steroid-induced ONFH susceptibility in the population of northern China, providing new evidence for the early detection and prevention of ONFH.

This paper aims to find a fertilization method that better matches the growth characteristics of vegetables and reduces the soil and environmental problems caused by unreasonable fertilization methods, in view of the strong buffering of the clayey black soil in the north and the mismatch between the amount of chemical fertilizer applied and the growth characteristics of vegetables during cultivation. In this experiment, Lactuca sativa L. (Lactuca sativa) was studied in a randomized complete block design in greenhouse and five different fertilizer application methods were arranged: exponential fertilization (EF), linear fertilization (LF), average fertilization (AF), one-time fertilization (OF), and no fertilization as a control group (CG). The effects of different fertilization methods on soil nutrients, agronomic traits of Lactuca sativa growth, and related quality were investigated, and the pattern of effects of different fertilization methods on growth and soil nutrients was obtained. The results of the experiment showed that the exponential fertilization method gradually took advantage as the growth time extended. The plant height (PLH), leaf length (LL), leaf width (LW), yield, soluble protein (SP), soluble sugar (SS), vitamin C (VC), and elemental nitrogen (EN) and potassium (EK) of Lactuca sativa were significantly improved under the exponential fertilization method compared with other fertilization methods, by 29.9 cm, 51.5 cm, 5.96 cm, 22, 2.32 kg/m2, 0.23%, 0.44%, 3.93%, 94.66 mg/kg, 1.58 g/kg, and 1.94 g/kg, respectively. The alkali-hydrolyzed nitrogen (SAN), available phosphorus (SAP), and available potassium (SAK) in the soil after fertilization were 139.69 mg/kg, 50.23 mg/kg, and 180.30 mg/kg, respectively. The above results showed that the exponential fertilization method not only improved the quality of Lactuca sativa and thus the quality of the crop growth traits, but also changed the soil nutrients favorably after fertilization, which is of some importance for the protection of black soils.

Abstract Background Dysregulation of the OPG/RANK/RANKL signalling pathway is a key step in the occurrence of steroid-induced osteonecrosis of the femoral head (ONFH). This study aims to understand the degree of methylation of the OPG, RANK, and RANKL genes in steroid-related ONFH. Methods A case-control study was designed, including 50 patients (25 males and 25 females) and 50 matched controls. The European Molecular Biology Open Software Suite (EMBOSS) was used to predict the existence and location of CpG islands in the OPG, RANK, and RANKL genes. The Agena MassARRAY platform was used to detect the methylation status of the above genes in the blood of subjects. The relationship between the methylation level of CpG sites in each gene and steroid-related ONFH was analysed by the chi-square test, logistic regression analysis, and other statistical methods. Results In the CpG islands of the OPG, RANK, and RANKL genes in patients with steroid-related ONFH, several CpG sites with high methylation rates and high methylation levels were found. Some hypermethylated CpG sites increase the risk of steroid-related ONFH. In addition, a few hypermethylated CpG sites have predictive value for the early diagnosis of steroid-related ONFH. Conclusion Methylation of certain sites in the OPG/RANK/RANKL signalling pathway increases the risk of steroid-related ONFH. Some hypermethylated CpG sites may be used as early prediction and diagnostic targets for steroid-related ONFH.

The pharmacokinetic profiles and bioequivalence of two cyclosporine oral solutions were investigated in cats. Twenty-four cats were randomly allocated to two equally sized treatment groups in a randomized four-cycle, and dual-sequence cross-over design. Test and reference articles were orally administered in a single dose of 7 mg/kg Bodyweight. Serial blood samples were collected, and blood cyclosporine concentration was determined by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). No significant differences were present in the major pharmacokinetic parameters (Cmax, AUC0−last,) between the two formulations. The blood profiles of cyclosporine following the administration of both formulations were similar. The findings of the study suggested that the two articles were bioequivalent for cyclosporine oral solution.

This study proposed an artificial intelligence (AI) approach for rapid, automatic detection of gasoline samples from different ignitable liquid samples based on their Raman spectra. The system integrated Raman spectroscopy, Raman signal transform, and transfer learning with a convolutional neural network (CNN). A hand-held Raman spectrometer was utilized to collect the learning dataset, including 180 gasoline spectra and 170 non-gasoline spectra from 17 various types of liquid samples. Continuous wavelet transform (CWT) was adopted to transform Raman spectra into image representations to facilitate transfer learning using a pre-trained CNN for image recognition. This approach streamlined AI model training, performance verification, and assessment. Experimental results showed that the CNN model could achieve 100% classification performance in precision, sensitivity, specificity, F1 score, and accuracy. The established AI model could be adopted for the Raman spectrum collected by different accessories, such as using the point-and-shoot attachment of liquid samples in glass vials. The experimental results suggested that CWT processing of Raman scattering signals enabled effective CNN transfer learning. The study demonstrated that CWT could be applied for Raman spectra processing to develop edge AI in forensic field testing of physical evidence.

Abstract Background Canine distemper virus (CDV) is an enveloped negative-strand RNA virus that exhibits a high mutation rate and continuously expands the range of hosts. Notably, CDV has infected giant panda with spill over from viral reservoirs in canines. Giant pandas (Ailuropoda melanoleuca), especially captive pandas, are known to be susceptible to natural infection with CDV. The high fatality rate of CDV poses a serious threat to the safety of the giant panda population. However, vaccines or drugs for canine distemper in giant pandas have not been developed to date. Therefore, a rapid test that can achieve accurate onsite detection of CDV is important to enable the timely implementation of control measures. In this study, we established a nucleic acid visualization assay for targeting the CDV N gene by using combines reverse transcription recombinase polymerase amplification with a closed vertical flow visualization strip (RT-RPA-VF). Results The RT-RPA-VF assay does not require sophisticated equipment, and it was determined to provide rapid detection at 35 °C for 30 min, while the limit of detection was 5 × 101 copies/μl RNA transcripts and 100.5 TCID50 ml− 1 viruses. The results showed that the assay was high specific to CDV and had no cross-reactivity with other viruses infecting the giant panda. Compared with RT-qPCR, RT-RPA-VF assay had a sensitivity of 100% and a specificity of 100% in 29 clinical samples. The coincidence rate between RT-RPA-VF and RT-qPCR was 100% (kappa = 1), indicating that the RT-RPA-VF assay possessed good diagnostic performance on clinical samples. Conclusions The RT-RPA-VF provides a novel alternative for the simple, sensitive, and specific identification of CDV and showed great potential for point of care diagnostics for captive and wild giant panda.

Abstract Background and purpose Alcohol-induced osteonecrosis of the femoral head (ONFH) is a complex and heterogeneous disease. Genetic factors and epigenetic modifications are one of the pathogenesis of the disease. However, the influence of epigenetic factors on the disease has not been systematically studied. Our research aims to determine the methylation changes of alcohol-induced ONFH. Methods An analytical cross-sectional study of a Chinese male population (50 alcohol-induced ONFH patients and 50 controls). The EpiTYPER of the Sequenom MassARRAY platform was used to detect the DNA methylation status of 132 cytosine-phosphate-guanine (CpG) sites in the OPG/RANKL/RANK gene promoter region. Results In the whole study group, the chi-square test was used to analyze the methylation rate between the two groups, and six CpG sites were found to be different, among which OPG1_CpG_2, OPG3_CpG_4, RANK1_CpG_6, RANK3_CpG_10, RANKL2_CpG_21, and RANKL2_CpG_46 in the case group were higher than those in the control group, while OPG4_CpG_2 was lower than that in the control group. The results showed that in patients with alcohol-induced ONFH, 146 CpG sites were examined for differences in methylation levels compared with healthy controls, 32 of which were not detected, and 23 of the remaining 114 sites showed differences in methylation levels compared with alcohol-induced ONFH patients. Receiver operator characteristic (ROC) curve analysis demonstrated the methylation levels of OPG/RANKL/RANK could efficiently predict the existence of alcohol-induced ONFH. Conclusion Our study of Chinese men suggests that several CpG sites in the OPG/RANKL/RANK gene in peripheral blood leukocytes of patients with alcohol-induced ONFH are in an abnormal methylation state (hypermethylation tended to be more frequent).

Abstract Background This study compared the biomechanics of artificial pedicle fixation in spine reconstruction with a 3-dimensional (3D)-printed prosthesis after total en bloc spondylectomy (TES) by finite element analysis. Methods A thoracolumbar (T10–L2) finite element model was developed and validated. Two models of T12 TES were established in combination with different fixation methods: Model A consisted of long-segment posterior fixation (T10/11, L1/2) + 3D-printed prosthesis; and Model B consisted of Model A + two artificial pedicle fixation screws. The models were evaluated with an applied of 7.5 N·m and axial force of 200 N. We recorded and analyzed the following: (1) stiffness of the two fixation systems, (2) hardware stress in the two fixation systems, and (3) stress on the endplate adjacent to the 3D-printed prosthesis. Results The fixation strength of Model B was enhanced by the screws in the artificial pedicle, which was mainly manifested as an improvement in rotational stability. The stress transmission of the artificial pedicle fixation screws reduced the stress on the posterior rods and endplate adjacent to the 3D-printed prosthesis in all directions of motion, especially in rotation. Conclusions After TES, the posterior long-segment fixation combined with the anterior 3D printed prosthesis could maintain postoperative spinal stability, but adding artificial pedicle fixation increased the stability of the fixation system and reduced the risk of prosthesis subsidence and instrumentation failure.

Macrolide antibiotics are important drugs to combat infections. The pharmacokinetics (PK) of these drugs are essential for the determination of their optimal dose regimens, which affect antimicrobial pharmacodynamics and treatment success. For most drugs, the measurement of their concentrations in plasma/serum is the surrogate for drug concentrations in target tissues for therapy. However, for macrolides, simple reliance on total or free drug concentrations in serum/plasma might be misleading. The macrolide antibiotic concentrations of serum/plasma, interstitial fluid (ISF), and target tissue itself usually yield very different PK results. In fact, the PK of a macrolide antibiotic based on serum/plasma concentrations alone is not an ideal predictor for the in vivo efficacy against respiratory pathogens. Instead, the PK based on drug concentrations at the site of infection or ISF provide much more clinically relevant information than serum/plasma concentrations. This review aims to summarize and compare/discuss the use of drug concentrations of serum/plasma, airway ISF, and tissues for computing the PK of macrolides. A better understanding of the PK of macrolide antibiotics based on airway ISF concentrations will help optimize the antibacterial dose regimen as well as minimizing toxicity and the emergence of drug resistance in clinical practice.

Abstract Chinese chestnut (Castanea mollissima Blume) seed kernels (CCSK) with high quality and quantity of starch has emerged as a potential raw material for food industry, but the molecular regulatory mechanism of starch accumulation in developing CCSK is still unclear. In this study, we firstly analyzed the fruit development, starch accumulation, and microscopic observation of dynamic accumulation of starch granules of developing CCSK from 10 days after flowering (DAF) to 100 DAF, of which six representative CCSK samples (50–100 DAF) were selected for transcriptome sequencing analysis. Approximately 40 million valid reads were obtained, with an average length of 124.95 bp, which were searched against a reference genome, returning 38,146 unigenes (mean size = 1164.19 bp). Using the DESeq method, 1968, 1573, 1187, 1274, and 1494 differentially expressed unigenes were identified at 60:50, 70:60, 80:70, 90:80 and 100:90 DAF, respectively. The relationship between the unigene transcriptional profiles and starch dynamic patterns in developing CCSK was comparatively analyzed, and the specific unigenes encoding for metabolic enzymes (SUSY2, PGM, PGI, GPT, NTT, AGP3, AGP2, GBSS1, SS1, SBE1, SBE2.1, SBE2.2, ISA1, ISA2, ISA3, and PHO) were characterized to be involved potentially in the biosynthesis of G-1-P, ADPG, and starch. Finally, the temporal transcript profiles of genes encoding key enzymes (susy2, pgi2, gpt1, agp2, agp3, gbss1, ss1, sbe1, sbe2.1, sbe2.2, isa1, isa2, isa3, and pho) were validated by quantitative real-time PCR (qRT-PCR). Our findings could help to reveal the molecular regulatory mechanism of starch accumulation in developing CCSK and may also provide potential candidate genes for increasing starch content in Chinese chestnut or other starchy crops.

Improvements in plant growth can bring great benefits to the forest industry. Eucalyptus urophylla is an important plantation species worldwide, and given that ploidy increases are often associated with plant phenotype changes, it was reasoned that its polyploidization may have good prospects and great significance toward its cultivation. In this study, the zygotic development period of E. urophylla was observed through paraffin sections, and a correlation between the development time of flower buds after pollination and the zygotic development period was established. On this basis, it was determined that the 25th day after pollination was the appropriate time for a high temperature to induce zygotic chromosome doubling. Then tetraploid E. urophylla was successfully obtained for the first time through zygotic chromosome doubling induced by high temperature, and the appropriate conditions were treating flower branches at 44°C for 6 h. The characterization of tetraploid E. urophylla was performed. Chromosome duplication brought about slower growing trees with thicker leaves, larger cells, higher net photosynthetic rates, and a higher content of certain secondary metabolites. Additionally, the molecular mechanisms for the variation in the tetraploid’s characteristics were studied. The qRT-PCR results showed that genes mediating the tetraploid characteristics showed the same change trend as those of the characteristics, which verified that tetraploid trait variation was mainly caused by gene expression changes. Furthermore, although the tetraploid had no growth advantage compared with the diploid, it can provide important germplasm resources for future breeding, especially for the creation of triploids.

The objectives of this study were to elucidate absorption, tissue distribution, excretion, and metabolism of vitacoxib, a novel selective cyclooxygenase-2 inhibitor, in Wistar rats. Vitacoxib was detected in most tissues within 15 min, suggesting that it was well distributed. Moreover, it could cross the intestinal barrier. Vitacoxib was mainly eliminated as two metabolites. Nine proposed metabolites of vitacoxib were found in the plasma, bile, urine, and feces of rats. Two main metabolites, 4-(4-chloro-1-(5-(methyl-sulfonyl) pyridin-2-yl)-1H-imidazol-5-yl) phenyl methanol (M1) and 4-(4-chloro-1-(5-(methyl-sulfonyl) pyridin-2-yl)-1H-imidazol-5-yl) benzoic acid (M2), were identified in rat feces and urine. Further, the authentic standards of M1 and M2 were synthesized to confirm their structures. The carboxylic acid derivative was the major metabolite of vitacoxib excreted in the urine and feces. Hydroxylation of the aromatic methyl group of vitacoxib and additional oxidation of the hydroxymethyl metabolite to a carboxylic acid metabolite were the proposed metabolic pathways. Vitacoxib displayed a high AUClast (4895.73 ± 604.34 ng·h/ml), long half-life (4.25 ± 0.30 h), slow absorption (Tmax, 5.00 ± 2.00 h), and wide tissue distribution in rats. Our findings provide significant information for the further development and investigation of vitacoxib as an effective nonsteroidal anti-inflammatory agent, and highly its potential for use future in a clinical setting.

Klebsiella pneumoniae complex is an increasingly important bacterial pathogen that is capable of causing severe organs and life-threatening disease. This study aimed to investigate the multidrug resistance, phylogroups, molecular characterization, and hypervirulence-associated determinants of the complex, which were isolated from clinical diseased dogs and cats. A total of 35 K. pneumoniae complex (2.3%; 95% confidence interval, 1.6–3.2) isolates were identified from 1,500 samples, all of which were collected randomly from veterinary hospitals in the 12 regions across China. Antimicrobial susceptibility testing showed that isolates were extremely resistant to amoxicillin–clavulanate (82.9%) and trimethoprim–sulfamethoxazole (77.1%). The rate of multidrug-resistant reached an astonishing 82.9% and found a carbapenemase-producing strain carrying IncX3-blaNDM−5 derived a cat from Zhejiang. The prevalence rates of extended-spectrum β-lactamase gene blaCTX−M and plasmid-mediated quinolone resistance gene aac(6')Ib-cr were 51.4% and 45.7%, respectively. The resistance gene aph(3')-Ia of isolates from cats was more significantly (p < 0.05) prevalent than that from dogs. Likewise, K. pneumoniae complex harbored hypervirulence-associated genes ybt (11.4%), iuc (5.7%), and iroB (2.9%). Three (8.6%) of the 35 isolates were determined as hypermucoviscous by the string test. Lipopolysaccharide serotype O1v2 had the highest percentage of 25.7%, but capsular serotypes presented diversity distribution among the isolates. The core–genome phylogenetic tree demonstrated most of the isolates belonged to the KpI phylogroup (91.4%). Multilocus sequence typing analysis identified 25 different STs; ST15 and ST37 were the most abundant accounting for isolates, followed by ST307, ST656, ST1408, and ST4566. In addition, the prevalence of IncFIB-type plasmid for cat isolates was significantly higher (p < 0.05) than that for dogs. Sequences of IncX3 in blaNDM−5-positive strain contained regions showing >99% nucleotide sequence identity to the reference plasmid pNDM-MGR194 from the human.

Abstract Background Gene polymorphism has an important influence on RETN gene expression level, and the increased level of resistin encoded in RETN will lead to metabolic disorder, especially lipid metabolism. Moreover, steroid-induced osteonecrosis of the femoral head (steroid-induced ONFH) is closely related to lipid metabolism level, so this study is intended to explore the relationship of RETN polymorphisms with susceptibility to steroid-induced ONFH in the Chinese Han population. Methods In this case-control study, eight single-nucleotide polymorphisms (SNPs) of RETN were genotyped by the Agena MassARRAY system in 199 steroid-induced ONFH patients and 200 healthy controls. The relationship between RETN polymorphisms and steroid-induced ONFH risk was assessed using genetic models and haplotype analyses. Odds ratio (OR) and 95% confidence intervals (CIs) were obtained by logistic regression adjusted for age. Results We found significant differences in the distribution of HDL-C, TG/HDL-C, and LDL-C/HDL-C between the patients and the control group (p

A feline panleukopenia virus (FPV), Giant panda/CD/2018, was isolated from a captive giant panda with mild diarrhea in 2018 in Chengdu, China, and further identified via indirect immunofluorescence assay (IFA), transmission electron microscopy (TEM) observation, and genetic analysis. Phylogenetic analysis based on the complete VP2 nucleotide sequences showed that it shared high homology with Chinese FPV isolates and grouped within FPV cluster 1. One unique substitution Gly(G)299Glu(E) in the capsid protein VP2 was first identified with Giant panda/CD/2018. The presence of the G299E substitution is notable as it is located on the top region of the interconnecting surface loop 3, which may be involved in controlling the host range and antigenicity of FPV. These findings first demonstrate that FPV with natural point mutation G299E in the VP2 gene is prevalent in giant panda and suggest that etiological surveillance and vaccination among all giant pandas are urgently needed to protect this endangered species against FPV infection.

The quantitative, accurate and efficient acquisition of tree phenotypes is the basis for forest “gene-phenotype-environment” studies. It also offers significant support for clarifying the genetic control mechanisms of tree traits. The application of unmanned aerial vehicle (UAV) remote sensing technology to the collection of phenotypic traits at an individual tree level quantitatively analyses tree phenology and directionally evaluates tree growth, as well as accelerating the process of forest genetics and breeding. In this study, with the help of high-resolution, high-overlap, multispectral images obtained by an UAV, combined with digital elevation models (DEMs) extracted from point clouds acquired by a backpack LiDAR, a high-throughput tree structure and spectral phenotypic traits extraction and a genetic selection were conducted in a trial of Eucalyptus clones in the State-owned Dongmen Forest Farm in the Guangxi Zhuang Autonomous Region. Firstly, we validated the accuracy of extracting the phenotypic parameters of individual tree growth based on aerial stereo photogrammetry point clouds. Secondly, on this basis, the repeatability of the tree growth traits and vegetation indices (VIs), the genetic correlation coefficients between the traits were calculated. Finally, the eucalypt clones were ranked by integrating a selection index of traits, and the superior genotypes were selected and their genetic gain predicted. The results showed a high accuracy of the tree height (H) extracted from the digital aerial photogrammetry (DAP) point cloud based on UAV images (R2 = 0.91, and RMSE = 0.56 m), and the accuracy of estimating the diameter at breast height (DBH) was R2 = 0.71, and RMSE = 0.75 cm. All the extracted traits were significantly different within the tree species and among the clones. Except for the crown width (CW), the clonal repeatability (Rc) of the traits were all above 0.9, and the individual repeatability values (Ri) were all above 0.5. The genetic correlation coefficient between the tree growth traits and VIs fluctuated from 0.3 to 0.5, while the best clones were EA14-15, EA14-09, EC184, and EC183 when the selection proportion was 10%. The purpose of this study was to construct a technical framework for phenotypic traits extraction and genetic analysis of trees based on unmanned aerial stereo photography point clouds and high-resolution multispectral images, while also exploring the application potential of this approach in the selective breeding of eucalypt clones.

Zearalenone(ZEA) is a kind of mycotoxin widely existing in nature, its toxic effects can lead to the reproductive disorders in humans and animals. The aim of this study was to investigate the mechanism of scutellarin against ovarian granulosa cell(GCs) injury induced by ZEA based on network pharmacology, molecular docking method. The results show that 293 drug targets of scutellarin were found from PhamMapper database, and 583 disease targets were selected from Genecards database. Finally, 57 scutellarin targets were obtained for the repair of GCs injury with gene intersection. The protein-protein interaction(PPI), gene ontology(GO) and kyoto encyclopedia of genes and genomes(KEGG) analysis indicated that MAPK signaling pathway was most likely activated by scutellarin. Scutellarin with JNK or Caspase-3 had minimal and negative free binding energy in molecular docking analysis, indicating that they might be the acting targets of scutellarin. Cell viability was significantly decreased in ZEA treated cells. However, GCs viability, the level of estradiol(E2) and progesterone(P4) were significantly increased with addition of scutellarin to ZEA treated cells. Western blot analysis showed that scutellarin significantly reduced the expression of JNK, c-jun and Cleaved-caspasee-3 in GCs compared with ZEA treatment. In conclusion, scutellarin could alleviate the ovarian GCs injury by down-regulating the expression of JNK, c-jun and Cleaved-caspase-3 through the activation of MAPK/JNK signaling pathway. Our results will provide a theoretical foundation for the treatment of reproductive disorders with scutellarin.