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Abstract Proper development of the placenta, the transient support organ forms after embryo implantation, is essential for a successful pregnancy. However, the regulation of trophoblast invasion, which is most important during placentation, remains largely unknown. Here, rats, mice, and pigs are used as biomedical models, used scRNA‐seq to comparatively elucidate the regulatory mechanism of placental trophoblast invasion, and verified it using a human preeclampsia disease model combined with scStereo‐seq. A dual‐featured type of immune‐featured trophoblast (iTrophoblast) is unexpectedly discovered. Interestingly, iTrophoblast only exists in invasive placentas and regulates trophoblast invasion during placentation. In a normally developing placenta, iTrophoblast gradually transforms from an immature state into a functional mature state as it develops. Whereas in the developmentally abnormal preeclamptic placenta, disordered iTrophoblast transformation leads to the accumulation of immature iTrophoblasts, thereby disrupting trophoblast invasion and ultimately leading to the progression of preeclampsia.

Abstract Background Yanghe Pingchuan decoction (YPD) has been used for asthma treatment for many years in China. We sought to understand the mechanism of YPD, and find more potential targets for YPD-based treatment of asthma. Methods An ovalbumin-induced asthma model in rats was created. Staining (hematoxylin and eosin, Masson) was used to evaluate the treatment effect of YPD. RNA-sequencing was carried out to analyze global gene expression, and differentially expressed genes (DEGs) were identified. Analysis of the functional enrichment of genes was done using the Gene Ontology database (GO). Analysis of signaling-pathway enrichment of genes was done using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Real-time reverse transcription-quantitative polymerase chain reaction was undertaken to measure expression of DEGs. Results Pathology showed that YPD had an improvement effect on rats with asthma. RNA-sequencing showed that YPD led to upregulated and downregulated expression of many genes. The YPD-based control of asthma pathogenesis may be related to calcium ion (Ca2+) binding, inorganic cation transmembrane transporter activity, microtubule motor activity, and control of canonical signaling (e.g., peroxisome proliferator-activated receptor, calcium, cyclic adenosine monophosphate). Enrichment analyses suggested that asthma pathogenesis may be related to Ca2 + binding and contraction of vascular smooth muscle. A validation experiment showed that YPD could reduce the Ca2 + concentration by inhibiting the Angiopoietin-II (Ang-II)/Phospholipase (PLA)/calmodulin (CaM0 signaling axis. Conclusion Control of asthma pathogenesis by YPD may be related to inhibition of the Ang-II/PLA/CaM signaling axis, reduction of the Ca2+ concentration, and relaxation of airway smooth muscle (ASM).

The roof breaking movement of steeply inclined and ultra-thick coal seam mining is complex, and the evolution law of stress and energy is special. Under the influence of deep ‘three highs and one disturbance’, the prevention and control of rock burst is not optimistic. Based on the experience of rock burst prevention and control in horizontal section mining of steeply inclined and ultra-thick coal seam after the rock burst accident in a mine in 2016, the experience of rock burst prevention and control in steeply inclined and ultra-thick coal seam in the past seven years is introduced in detail from the mechanism of rock burst in horizontal section mining of steeply inclined and ultra-thick coal seam, the comprehensive prevention and control of gas outburst and rock burst and the management of rock burst. In terms of the mechanism of rock burst, the inclined cantilever beam model of roof strata is established, the evolution process of fracture instability of roof and floor overburden structure is revealed, and the ‘clamping theory’ of rock burst in steeply inclined and ultra-thick coal seam is put forward. In terms of comprehensive prevention and control of gas outburst and rock burst, based on the theory of strength weakening and rock burst reduction of rock burst disaster control and disaster relief technology, combined with the original outburst prevention measures system, this paper puts forward the measures that can prevent and benefit the outburst prevention, forms a mine gas/carbon dioxide outburst/rock burst ‘integrated control’ technology system, and establishes a rock burst prevention and control system suitable for the horizontal section mining of steeply inclined thick coal seam in a mine. The intensity of gas outburst prevention and control is verified by the amount of drilling cuttings and the value of gas absorption and desorption. At the same time, the distribution of microseismic events and the total frequency and energy of each energy level are compared in the working face with pressure relief measures. The effectiveness of the control effect of the pressure relief scheme is demonstrated. In terms of rock burst management, a “six-in-one” comprehensive prevention and control framework has been formed, including prediction and evaluation, monitoring and early warning, treatment and prevention, effect test, safety protection and education and training. Based on the “Coal Mine Safety Regulations” and “Detailed Rules for Prevention and Control of Coal Mine Rock Burst” and other provisions, the Q/YJMD-FC 0104-2022“Yaojie Coal and Electricity Group Co., Ltd. Coal Mine Rock Burst Prevention and Control Part IV: Technical Specification for Prevention and Control of Rock Burst” was formulated.

Abstract Background One of the most critical periods for the loss of pig embryos is the 12th day of gestation when implantation begins. Recent studies have shown that non-coding RNAs (ncRNAs) play important regulatory roles during pregnancy. Circular RNAs (circRNAs) are a kind of ubiquitously expressed ncRNAs that can directly regulate the binding proteins or regulate the expression of target genes by adsorbing micro RNAs (miRNA). Results We used the Illumina Novaseq6,000 technology to analyze the circRNA expression profile in the endometrium of three Erhualian (EH12) and three Yorkshire (YK12) pigs on day 12 of gestation. Overall, a total of 22,108 circRNAs were identified. Of these, 4051 circRNAs were specific to EH12 and 5889 circRNAs were specific to YK12, indicating a high level of breed specificity. Further analysis showed that there were 641 significant differentially expressed circRNAs (SDEcircRNAs) in EH12 compared with YK12 (FDR

Abstract Background 2-Pyrone-4,6-dicarboxylic acid (PDC), a chemically stable pseudoaromatic dicarboxylic acid, represents a promising building block for the manufacture of biodegradable polyesters. Microbial production of PDC has been extensively investigated, but low titers and yields have limited industrial applications. Results In this study, a multi-step biosynthesis strategy for the microbial production of PDC was demonstrated using engineered Escherichia coli whole-cell biocatalysts. The PDC biosynthetic pathway was first divided into three synthetic modules, namely the 3-dehydroshikimic acid (DHS) module, the protocatechuic acid (PCA) module and the PDC module. Several effective enzymes, including 3-dehydroshikimate dehydratase for the PCA module as well as protocatechuate 4,5-dioxygenase and 4-carboxy-2-hydroxymuconate-6-semialdehyde dehydrogenase for the PDC module were isolated and characterized. Then, the highly efficient whole-cell bioconversion systems for producing PCA and PDC were constructed and optimized, respectively. Finally, the efficient multi-step biosynthesis of PDC from glucose was achieved by smoothly integrating the above three biosynthetic modules, resulting in a final titer of 49.18 g/L with an overall 27.2% molar yield, which represented the highest titer for PDC production from glucose reported to date. Conclusions This study lays the foundation for the microbial production of PDC, including one-step de novo biosynthesis from glucose as well as the microbial transformation of monoaromatics.

LncRNA OIP5-AS1 has a common gene imbalance in various cancers and tumours, which plays an important role in regulating its biological function. However, there are few studies on lncRNA OIP5-AS1 in rheumatoid arthritis (RA). The purpose of the present study was to investigate the role of lncRNA OIP5-AS1 in the pathogenesis of RA. In the present study, we established an adjuvant arthritis (AA) rat model to obtain primary fibroblast-like synoviocytes (FLSs);The subcellular localisation of lncRNA OIP5-AS1 was detected by fluorescence in situ hybridisation (FISH) assay; Cell proliferation of FLSs was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay;IL-1β, IL-6 and TNF-α concentrations were measured by enzyme-linked immunosorbent assay (ELISA);Quantitative real-time PCR (qRT-PCR), Western blots(WB) and immunofluorescence were used to detect the expression of lncRNA OIP5-AS1/miR-410-3p/wnt7b signal axis and Wnt/β-catenin signal pathway related indicators in FLSs. FISH assay confirmed the presence of lncRNA OIP5-AS1 in the cytoplasm, suggesting that it acts as a competing endogenous RNA (ceRNA). qRT-PCR showed that the expression of lncRNA OIP5-AS1 was upregulated in FLSs, while the expression of miR-410-3p was downregulated in FLSs. We also found that lncRNA OIP5-AS1 knockdown inhibited the proliferation and inflammation of FLSs. Moreover, the expression of Wnt7b, the downstream target gene of miR-410-3p, and the activation of the Wnt/β-catenin signalling pathway were also inhibited by lncRNA OIP5-AS1 knockdown. These results suggested that lncRNA OIP5-AS1 promotes the activation of the Wnt/β-catenin signalling pathway by regulating the miR-410-3p/Wnt7b signalling axis, thereby participating in the occurrence and development of RA.

Background: Yanghe Pingchuan Granule (YPG) is a patented Chinese medicine developed independently by the Anhui Provincial Hospital of Traditional Chinese Medicine. For many years, it has been used for the treatment of asthma with remarkable clinical effects. However, the composition of YPG is complex, and its potential active ingredients and mechanism of action for the treatment of asthma are unknown. Materials and methods: In this study, we investigated the potential mechanism of action of YPG in the treatment of asthma through a combination of bioinformatics and in vivo experimental validation. We searched for active compounds in YPG and asthma targets from multiple databases and obtained common targets. Subsequently, a protein-protein interaction (PPI) network for compound disease was constructed using the protein interaction database for Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Finally, hematoxylin and eosin (H&E) staining, Masson staining, enzyme-linked immunosorbent assay (ELISA) analysis, immunofluorescence (IF) experiments, and Western blot (WB) experiments were performed to verify the possible mechanism of action of YPG for asthma treatment. Results: We obtained 72 active ingredients and 318 drug target genes that overlap with asthma. Serine/threonine-protein kinase (AKT1), tumor protein p53 (TP53), tumor necrosis factor (TNF), interleukin (IL)-6, IL-1β, vascular endothelial growth factor-A (VEGFA), prostaglandin-endoperoxide synthase 2 (PTGS2), caspase-3 (CASP3), mitogen-activated protein kinase 3 (MAPK3) and epidermal growth factor receptor (EGFR) were the most relevant genes in the PPI network. KEGG analysis showed a high number of genes enriched for the nuclear factor kappa-B (NF-κB) signaling pathway. Animal experiments confirmed that YPG reduced inflammatory cell infiltration and down-regulated the expression of ovalbumin-induced inflammatory factors. Furthermore, YPG treatment decreased the protein expression of NFĸB1, nuclear factor kappa B kinase subunit beta (IKBKB), vascular endothelial growth factor (VEGF), and vascular endothelial growth factor receptor 2 (VEGFR2) in lung tissue. Conclusion: YPG has a positive effect on asthma by interfering with multiple targets. Furthermore, YPG may significantly inhibit the follicle-induced inflammatory response through the NF-ĸB signaling pathway.

In this study, the function of a non-ribosomal peptide synthetase-like (NRPS-like) encoding gene AOL_s00188g306 (g306) was investigated to reveal the association between NRPS and nematocidal activity in the nematode-trapping fungus Arthrobotrys oligospora. Sequence analysis indicated that the encoded product of g306 is an adenylation domain of non-ribosomal peptide synthetases and extended short-chain dehydrogenase/reductase domain-containing proteins, and displays a wide substrate spectrum. The Δg306 mutants were more sensitive to chemical stressors than the wild type. Disruption of g306 impeded the nematocidal efficiency of A. oligospora. Metabolomics analysis showed that secondary metabolite biosynthesis and lipid metabolism were altered in the mutants. The phenotypic changes in the mutants can be attributed to the down-regulation of various metabolites, including fatty acyls, prenol lipids, steroidsand steroid derivative, and amino acid derivatives, identified in the present study. This study investigated the association between the non-ribosomal polypeptide-encoding gene g306 and nematicidal activity in A. oligospora, providing a reference for resolving the predation mechanism of nematode-trapping fungus.

In recent years, the synergy between artificial intelligence and turbulence big data has given rise to a new data-driven paradigm in turbulence research. Data-driven turbulence modeling has emerged as one of the forefront directions in fluid mechanics. Most existing studies focus on feature construction, selection, and the development of modeling frameworks, often overlooking the practical deployment and application of trained models. This paper examines the entire process from model construction to real-world deployment, using data-driven turbulence modeling for high Reynolds number flows over complex three-dimensional configurations as a case study. Key stages include data generation, input-output feature construction, model training, model compilation and optimization, deployment, and validation. We successfully implemented the entire workflow in a heterogeneous supercomputing environment and, through mixed programming techniques, integrated the resulting turbulence model into the Platform for Hybrid Engineering Simulation of Flows (PHengLEI) open-source software framework. This allowed for mixed-precision simulations, with the main equations solved in double precision and the turbulence model in half precision. The new computational framework was validated through large-scale parallel numerical simulations on grids with tens of millions of elements for three-dimensional complex configurations. The results highlight the efficiency of our model deployment, with overall computational efficiency improving by 13.35% and the turbulence model’s solution speed increasing by approximately 3.9 times. The accuracy of the computations was also confirmed, with the average relative error in the lift and drag coefficients calculated by the data-driven turbulence model within 3%. Across various computing nodes, the relative error in the computed aerodynamic coefficients remained within 1%, demonstrating the framework’s scalability. Notably, our contributions have been incorporated as a case study in the latest PHengLEI open-source project ^5 .

Ferroptosis is a newly discovered form of non-apoptotic regulatory cell death driven by iron-dependent lipid peroxidation. Ferroptosis significantly differs from other forms of cell death in terms of biochemistry, genetics, and morphology. Ferroptosis affects many metabolic processes in the body, resulting in disruption of homeostasis, and is related to many types of lung disease. Although current research on ferroptosis remains in the early stage, existing studies have confirmed that ferroptosis is regulated by a variety of genes, mainly involving changes in genes involved in iron homeostasis and lipid peroxidation metabolism. Furthermore, the mechanism of ferroptosis is complex. This review summarizes the confirmed mechanisms that can cause ferroptosis, including activation of glutathione peroxidase 4, synthesis of glutathione, accumulation of reactive oxygen species, and the influence of ferrous ions and p53 proteins. In recent years, the mechanism of ferroptosis in the occurrence and development of many diseases has been studied; the occurrence of ferroptosis will produce an inflammatory storm, and most of the inducing factors and pathological manifestations of lung diseases are also inflammatory reactions. Therefore, we believe that the association between ferroptosis and lung disease deserves further study. This article aims to help readers to better understand the mechanism of ferroptosis, provide new ideas and targets for the treatment of lung diseases, and point out the direction for the development of new targeted drugs for the clinical treatment of lung diseases.

Respiration monitoring is a promising alternative to medical diagnosis of several diseases. However, current techniques of respiration monitoring often require expensive and cumbersome devices which greatly limit their medical applications. Here, we present a fully integrated wearable device consisting of a flexible LCP-copper interdigital electrode, a sensing layer and a wireless electrochemical analysis system. The developed humidity sensor exhibits a high sensitivity, a good repeatability and a rapid response/recover time. The long-term stability is over 30 days at different relative humidity. By integrating the flexible humidity sensor with miniaturized electrochemical analysis system (0.8 cm × 1.8 cm), response current concerning respiration can be wirelessly transmitted to App-assisted smartphone in real time. Furthermore, the fabricated humidity sensor can realize skin moisture monitoring in a touch-less way. The large-scale production of miniaturized flexible sensor (4 mm × 6 mm) has significantly contributed to commercial deployment.

Intestinal microenvironment dysbiosis is one of the major causes of diseases, such as obesity, diabetes, inflammatory bowel disease, and colon cancer. Microbiota-based strategies have excellent clinical potential in the treatment of repetitive and refractory diseases; however, the underlying regulatory mechanisms remain elusive. Identification of the internal regulatory mechanism of the gut microbiome and the interaction mechanisms involving bacteria-host is essential to achieve precise control of the gut microbiome and obtain effective clinical data. Gut bacteria-derived extracellular vesicles (GBEVs) are lipid bilayer nanoparticles secreted by the gut microbiota and are considered key players in bacteria-bacteria and bacteria-host communication. This review focusses on the role of GBEVs in gut microbiota interactions and bacteria-host communication, and the potential clinical applications of GBEVs.

Taohong siwu decoction (THSWD) has been shown to have a therapeutic effect on ischemic strokes (IS). However, it is not clear to us whether THSWD reduces deoxyribonucleic acid (DNA) damage after stroke and reduces the inflammatory response caused by the damage. Therefore, we constructed an IS model (I/R) in rats and performed oxygen-glucose deprivation/reoxygenation (OGD/R) on BV2 cells. Then ELISA, immunofluorescence staining, immunohistochemistry staining, and RT-qPCR were performed to detect the expressions of absent in melanoma 2 (AIM2), NLRC4, and Caspase-1 inflammasomes and other inflammatory factors. Experimental stroke causes DNA damage, and we found that the aforementioned inflammasomes as well as inflammatory factors were significantly inhibited after treatment with THSWD by comparing the model group with the model administration group. In addition, we examined the expression of AIM2, NLRC4, and Caspase-1 in BV2 cells of OGD/R and found that the expression of the aforementioned inflammasomes was significantly decreased in OGD/R by administration of THSWD-containing serum. Our data suggest that THSWD can reduced DNA damage after stroke as well as the inflammatory response caused by the damage.

Background The detection rate of bilateral multiple pulmonary nodules (BMPNs) is increasing due to widespread use of chest computed tomography (CT) screening. However, there is no consensus on the treatment options for BMPNs and whether simultaneous bilateral pulmonary resection is safe remains controversial. The purpose of this study was to evaluate the feasibility and safety of simultaneous bilateral pulmonary resection for BMPNs. Methods A total of 16 consecutive patients with BMPNs who underwent simultaneous bilateral pulmonary resection in Beijing Hospital from June 2013 to July 2020 were enrolled in this study. Clinical characteristics, imaging and pathological features, and perioperative outcomes were retrospectively reviewed. Results There were 10 males and six females included in the study with a mean age of 61.9 (range: 39–78) years. A total of 35 nodules were resected in 16 patients including 12 patients with bilateral primary lung cancer, three patients with primary lung cancer on one side and a benign nodule on the contralateral side, and one patient with bilateral benign nodules. All patients underwent bilateral pulmonary resection via single‐utility port video‐assisted thoracoscopic surgery (VATS). Nine, four, two, and one patients underwent lobectomy with contralateral segmentectomy or wedge resection, segmentectomy with contralateral wedge resection, bilateral segmentectomy and bilateral wedge resection, respectively. All operations were accomplished successfully without intraoperative blood transfusion, conversion to thoracotomy, major complication and postoperative 90‐day death. The mean operation time was 220.1 ± 65.6 minutes, median thoracic drainage duration was four days (range: 2–8 days), mean pleural drainage was 1387.5 ± 694.7 mL, and median postoperative hospital stay was seven days (range: 5–18 days). There were three cases (18.8%) of minor complications, including one case of pulmonary air leakage, one case of atrial fibrillation, and one case of poor healing of surgical site. A total of 50% (8/16) of the patients had severe postoperative pain and required additional analgesia. Conclusions For selected patients, simultaneous bilateral pulmonary resection via single‐utility port VATS is a safe and feasible minimally invasive procedure for BMPNs. Adequate postoperative analgesia via a multimodal analgesia strategy should be used to prevent postoperative pain. Key points Significant findings of the study The incidence of major complication after minimally invasive bilateral pulmonary resection is low for patients with good pulmonary function, but there is a relatively high incidence of minor complications and pain at the surgical site. Adequate postoperative analgesia via multimodal analgesia strategy should be used to prevent postoperative pain. What this study adds For the treatment of bilateral multiple pulmonary nodules, simultaneous bilateral pulmonary resection via single‐utility port video‐assisted thoracoscopic surgery is safe and feasible for selected patients.

In the process of high-efficiency milling of titanium alloys, cutting vibration causes the frequent changes in the contact relationship between the flank face of the cutter tooth and the workpiece. The instantaneous friction speed, friction force and energy consumption of the milling cutter thus change continuously, resulting in the difficulty to precisely control the wear and life of milling cutter. This has become a bottleneck of restricting the further improvement of the cutting performance of high energy efficiency milling cutter. In this work, the model of instantaneous friction velocity and friction energy consumption of the flank face of the cutter tooth under vibration are developed. The distribution and evolution of instantaneous friction speed and friction energy consumption are studied. The proposed models are verified by high-efficiency milling experiments. The results show that the average relative error of the proposed model is 10.05%, by using this model, the influences of the cutting vibration on instantaneous friction energy consumption and friction wear boundaries could be effectively unveiled. The proposed model also could accurately describe the distribution and evolution of the above-mentioned parameters.

The mechanism of action of Naoluo Xintong decoction (NLXTD) for the treatment of ischemic stroke (IS) is unknown. We used network analysis and molecular docking techniques to verify the potential mechanism of action of NLXTD in treating IS. The main active components of NLXTD were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and IS targets were collected from the Online Mendelian Inheritance in Man (OMIM), GeneCards, and Drugbank databases; their intersection was taken. In addition, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed and used to build protein-protein interaction networks. AutoDock Vina software was used for molecular docking, and animal experiments were conducted to verify the results. Hematoxylin and eosin staining was used to observe the brain morphology of rats in each group, and real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression level of relative mRNA in the brain tissue of rats. Western blot was used to detect the expression level of relative protein in the brain tissue of rats. Network analysis and molecular docking results showed that CASP3, NOS3, VEGFA, TNF, PTGS2, and TP53 are important potential targets for NLXTD in the treatment of IS. RT-qPCR and western blot results showed that NLXTD inhibited the expression of CASP3, TNF, PTGS2, and TP53 and promoted the expression of VEGFA and NOS3. NLXTD treats IS by modulating pathways and targets associated with inflammation and apoptosis in a multicomponent, multitarget manner.

Background and objective Interstitial lung disease (ILD) is a group of diffuse lung diseases that mainly involve the interstitial and alveolar cavities and result in loss of alveolar-capillary functional units, leading to restrictive ventilatory dysfunction and diffusion impairment. There was an increased incidence of lung cancer on the basis of ILD, and perioperative risk of patients with lung cancer combined with ILD (LC-ILD) was significantly increased. The aim of this study is to summarize the safety and experience of surgical treatment of LC-ILD. Methods A retrospective analysis was performed on 23 patients with LC-ILD who underwent pneumonectomy in Beijing Hospital from January 2012 to December 2019, and their clinical manifestations, image feature, pathology, surgical safety, perioperative complications and treatment experience were summarized. Results A total of 23 patients were included in this study, including 20 males (87.0%) with an average age of (69.1±7.8) years, and 19 cases (82.6%) were smokers. Of the ILD types, 14 cases (60.9%) were idiopathic pulmonary fibrosis, 7 cases (30.4%) were idiopathic nonspecific interstitial pneumonia, and 2 (8.7%) were interstitial lung disease associated with connective tissue diseases. The pathology of lung cancer included adenocarcinoma (30.4%, 7/23), small cell carcinoma (30.4%, 7/23), squamous cell carcinoma (26.1%, 6/23), small cell carcinoma mixed with squamous cell carcinoma (4.3%, 1/23) and large cell neuroendocrine carcinoma (8.7%, 2/23). Surgical approaches included video assisted thoracoscopy (69.6%, 16/23) and anterolateral thoracotomy (30.4%, 7/23), with lobectomy (52.2%, 12/23), double lobectomy (4.3%, 1/23), and sublobectomy (39.1%, 9/23). There were 11 cases (47.8%) of postoperative complications, including 8 cases (34.8%) of pulmonary complications, 4 cases (17.4%) of acute exacerbation of ILD (AE-ILD), 6 cases (26.1%) of atrial fibrillation, and 1 case (4.3%) of acute left ventricular dysfunction. The 90-day mortality is 8.7% (2/23) and the cause of death was acute exacerbation of ILD. Conclusion Most of LC-ILD were elderly patients with multiple comorbidities and decreased pulmonary function, leading to significantly increased surgical risk. The ILD should be fully evaluated and controlled before surgery, intraoperative trauma should be minimized, and special attention should be paid to pulmonary complications and AE-ILD after surgery. Postoperative AE-ILD has a poor prognosis and glucocorticoids may be effective. Early diagnosis and treatment is the key to treatment of AE-ILD.

Abstract Phytases are widely utilized in feed industry to increase the utilization of phosphorus, minerals, and amino acids for improvement of animal and human nutrition. At present, all known β-propeller phytases (BPP) have been generated from bacteria, particularly Bacillus. In this work we report for the first time a new fungal-derived BPP phytase. We identified a phytase highly differentially expressed only in the parasitic stage of a nematophagous fungus, Arhtrobotrys oliogospora, during the development of the 3D traps. We found that this phytase was homologous to the known bacterial BPP phytase, thus we referred the new phytase to Aophytase. The heterologous expression of codon-optimized Aophytase gene in Pichia pastoris was successfully investigated to yield recombinant Aophytase (r-Aophytase) with high specific enzyme activity of 74.71 U/mg, much higher than those of recombinant BPP phytases derived bacteria. The kinetic parameters of the r-Aophytase, the optimum pH and temperature, as well as the effects of surfactant, EDTA and different ions on its enzyme activity were further investigated. The potential utilization of r-Aophytase in feed processing was finally explored. We found that the optimal pH value was about 7.5, and the optimal temperature was 50 °C.; r-Aophytase significantly increased the release of inorganic phosphorus from soybean meal, and improved the release of soluble minerals from the durum wheat flour and finger millet flour. The findings indicate its potential utilization in the feed processing to ameliorate nutritional value of cereals and animal feed in the future.

Backgroud and objective Thymectomy plays an important role in patients with myasthenia gravis (MG) and video-assisted thoracoscopic (VATS) extended thymectomy has been widely used in recent years. The traditional thoracoscopic procedure requires three intercostal incisions. Our study improved the surgical approach and operation method by using single-utility port thoracoscopy. The aim of this study was to evaluate the effect of single-utility port VATS extended thymectomy for MG. Methods A retrospective analysis was performed in 45 patients with MG who underwent single-utility port VATS extended thymectomy in Beijing Hospital from July 2017 to December 2018. The safety and effectiveness of this surgical approach were summarized. Results All operations were accomplished successfully, without conversion to thoracotomy, requirement of additional incisions or postoperative death. The mean operation time was (141.3±39.2) min; the mean intraoperative blood loss was (64.2±45.5) mL; the median thoracic drainage duration was 3 days (range 2 days to 8 days); the mean pleural drainage was (890.4±439.1) mL, and the median postoperative hospital stay was 6 days (range 3 days to 91 days). There were 13 cases (28.9%) with postoperative complications, including 5 cases (11.1%) with myasthenia crisis, 6 cases (13.3%) with pulmonary complications, 4 cases (8.9%) with poor incision healing, 4 cases (8.9%) with atrial fibrillation, and 1 case (2.2%) with delayed pericardial hemorrhage. The median follow-up time was 18.5 months (range 12.5 months to 29.2 months). According to the effect of 1 year after surgery, 1 case (2.2%) showed pharmacologic remission; 18 cases (40.0%) showed minimal manifestations; 23 cases (51.1%) got improvement; 1 case (2.2%) showed no changs and 2 cases (4.4%) were worse. Conclusion Single-utility port VATS extended thymectomy is a safe and feasible minimally invasive procedure for MG. During the perioperative period, special attention should be paid to prevent myasthenic crisis, pulmonary complications, and incision complications.

Nematode-trapping fungus (NTF) is a crucial predator of nematodes, which can capture nematodes by developing specific trapping devices. However, there is limited understanding of the role and mechanism of cell surface proteins attached to the surface of mycelia or trapping cells. Here, the effects of a putative GPI-anchored protein-encoding gene Aog185 on the growth and nematode-trapping efficiency of A. oligospora were investigated. Compared to the wild-type (WT) strain, the ΔAog185 mutant grew more slowly, exhibited a 20% decrease in conidiation, delayed conidial germination, generated fewer traps, attenuated nematode trapping efficiency, and was more sensitive to chemical stressors. Transcriptomic analysis indicated that a large number of transmembrane transport-related genes were differentially expressed between the WT and ΔAog185 mutant strains. Aog185 deletion could damage the intrinsic components of the membrane and cytoskeleton. Specifically, knockout of Aog185 disrupted transmembrane transport homeostasis during the phagocytosis, cell autophagy, and oxidative phosphorylation processes, which were associated with the fusion of cells and organelle membranes, transport of ions and substrates, and energy metabolism. Hence, the putative GPI-anchored protein-encoding gene Aog185 may contribute to the lifestyle switch of NTF and nematode capture, and the effect of Aog185 gene on cell transmembrane transport is considered key to this process. Our findings provide new insights into the mechanism of Aog185 gene during the process of nematode trapping by NTF.

Bronchial asthma (BA) is a chronic inflammatory disease of the airway. Previous research has shown that Yanghe Pingchuan granules (YPGs) exert a precise therapeutic effect on BA. In our previous work, we showed that YPGs improved inflammation of the airways in rat models of BA. Other studies have shown that the pathogenesis of BA is closely related to pyroptosis and that the TOLL-like receptor pathway plays a key role in the mediation of pyroptosis. Therefore, in the present study, we established a rat model of BA by applying the concept of pyroptosis and used the TLR4/NF-κB/NRLP3 signaling pathway as the target and YPGs as the treatment method. We evaluated the effects of YPGs on airway inflammation and pyroptosis in the model rats by HE staining, Masson’s staining, AP-PAS staining, western blotting, and real-time quantitative PCR. The results showed that Yanghe Pingchuan granules could significantly improve the inflammatory response of bronchial tissue in BA rats, reduce the content of inflammatory factors IL-1β and IL-18, and inhibit the expression of pyroptosis factor. Meanwhile, YPG can block the TLR4/NF-κB signaling pathway. These findings suggest that YPG may be an effective drug for the treatment of BA by blocking the TLR4/NF-κB signaling pathway and inhibiting pyroptosis.

In higher fungi, lysine is biosynthesized via the α-aminoadipate (AAA) pathway, which differs from plants, bacteria, and lower fungi. The differences offer a unique opportunity to develop a molecular regulatory strategy for the biological control of plant parasitic nematodes, based on nematode-trapping fungi. In this study, in the nematode-trapping fungus model Arthrobotrys oligospora, we characterized the core gene in the AAA pathway, encoding α-aminoadipate reductase (Aoaar), via sequence analyses and through comparing the growth, and biochemical and global metabolic profiles of the wild-type and Aoaar knockout strains. Aoaar not only has α-aminoadipic acid reductase activity, which serves fungal L-lysine biosynthesis, but it also is a core gene of the non-ribosomal peptides biosynthetic gene cluster. Compared with WT, the growth rate, conidial production, number of predation rings formed, and nematode feeding rate of the ΔAoaar strain were decreased by 40–60%, 36%, 32%, and 52%, respectively. Amino acid metabolism, the biosynthesis of peptides and analogues, phenylpropanoid and polyketide biosynthesis, and lipid metabolism and carbon metabolism were metabolically reprogrammed in the ΔAoaar strains. The disruption of Aoaar perturbed the biosynthesis of intermediates in the lysine metabolism pathway, then reprogrammed amino acid and amino acid-related secondary metabolism, and finally, it impeded the growth and nematocidal ability of A. oligospora. This study provides an important reference for uncovering the role of amino acid-related primary and secondary metabolism in nematode capture by nematode-trapping fungi, and confirms the feasibility of Aoarr as a molecular target to regulate nematode-trapping fungi to biocontrol nematodes.

BackgroundTao Hong Si Wu Decoction (THSWD) is a well-known traditional Chinese medicine used clinically alone or combined with drugs to treat breast cancer. However, there has been no study to date on the underlying mechanisms of its therapeutic effects.ObjectivesTo explore the potential mechanism of THSWD for the treatment of breast cancer using network pharmacology and experimental research.MethodsThe active ingredients of THSWD were screened according to Lipinski’s rule of five based on the 107 ingredients of THSWD identified by UPLC-Q-TOF-MSE. The targets of THSWD and breast cancer from multiple databases were collected, and a Compound-Target-Pathway network based on protein-protein interaction (PPI) was constructed. Gene ontology (GO) analysis and KEGG pathway analysis were performed via the DAVID server. Molecular docking studies verified the selected key ingredients and key targets. The results of network pharmacology were verified by in vitro experiments. Including the effects of THSWD drug-containing rat serum (THSWD serum) on cell proliferation, and on the targets HRAS, MAPK1, AKT1, GRB2, and MAPK14 were assayed by RT-qPCR and Western blot assays.ResultsIn total, 27 active ingredients including 8 core components, were obtained from 107 ingredients and 218 THSWD target genes for the treatment of breast cancer were identified. THSWD is active in the treatment of breast cancer by targeting Ras, FoxO, PI3K-Akt and other signaling pathways. MCF-7 and MDA-MB-231 cell proliferation was inhibited by THSWD serum in a time and concentration dependent manner. THSWD could regulated the RNA and protein expression of core targets HRAS, MAPK1, AKT1, GRB2, and MAPK14 for treatment of breast cancer.ConclusionThe results of network pharmacology study showed that THSWD is active against breast cancer by intervening with multiple targets and pathways. Luteolin, kaempferol, senkyunolide E, and other 8 compounds may be the core active ingredients of THSWD in the treatment of breast cancer. THSWD treatment of breast cancer may be related to targeting Ras, FoxO, PI3K-Akt, and other signal pathways associated with the core targets HRAS, MAPK1, AKT1, GRB2, and MAPK14.

Background and objective DNA polymerase β is one of the key enzymes for DNA repair and it was reported that about 30 percent of different types of cancers carried mutations in its coding gene Polb. However, it is still controversial whether it is true or false because of the small sample size in these studies. In current study, we performed genetic screening of promoter and coding regions of Polb gene in 69 Chinese lung cancer patients using Sanger sequencing method, so as to elucidate real mutation frequency of Polb mutations in Chinese Han population. Methods Salting out extraction method was used to get the genome DNAs from tumor and normal matched tissues of 69 lung cancer patients. The promoter and 14 coding regions of Polb gene were then amplified using these DNAs as the template. After purification, amplicons were sequenced and aligned to the wild type Polb gene in NCBI database, in order to find out the mutated sites of Polb gene in Chinese lung cancer patients. Results In this study, we totally found only 5 mutated sites in Polb gene. In detail, 3 mutations (-196G>T, -188_-187insCGCCC, -168C>A) were located in the promoter region; 2 mutations (587C>G, 612A>T) were found in coding regions. Specially, mutations of -188_-187insCGCCC and 587C>G (resulting to the amino acid substitution of Thr to Ser at position 196) had never been reported by other groups before. However, all these 5 mutated sites could be detected in both tumor and matched normal tissues, which inferred that they are not lung tumor specific mutations. Conclusion No lung tumor specific mutations of Polb gene could be found in Chinese lung cancer patients and Polb gene mutation might not be a molecular marker for Chinese lung cancer patients.

Operational safety in the airport is the focus of the aviation industry. Target recognition under low visibility plays an essential role in arranging the circulation of objects in the airport field, identifying unpredictable obstacles in time, and monitoring aviation operation and ensuring its safety and efficiency. From the perspective of transfer learning, this paper will explore the identification of all targets (mainly including aircraft, humans, ground vehicles, hangars, and birds) in the airport field under low-visibility conditions (caused by bad weather such as fog, rain, and snow). First, a variety of deep transfer learning networks are used to identify well-visible airport targets. The experimental results show that GoogLeNet is more effective, with a recognition rate of more than 90.84%. However, the recognition rates of this method are greatly reduced under the condition of low visibility; some are even less than 10%. Therefore, the low-visibility image is processed with 11 different fog removals and vision enhancement algorithms, and then, the GoogLeNet deep neural network algorithm is used to identify the image. Finally, the target recognition rate can be significantly improved to more than 60%. According to the results, the dark channel algorithm has the best image defogging enhancement effect, and the GoogLeNet deep neural network has the highest target recognition rate.

Abstract In this paper, we consider the Dirichlet boundary value problem to singular semilinear subelliptic equation on the Heisenberg group − Δ H u = 1 u γ + f ( u ) , γ > 0 . $$-\Delta_{\mathbb{H}}u=\frac{1}{u^{\gamma}}+f(u), \quad \gamma>0. $$ We prove the positivity and continuity up to the boundary for the weak solutions. We also conclude monotonicity of cylindrical solutions to the problem based on a study of the equation − Δ H u 0 = 1 u 0 γ $-\Delta_{\mathbb {H}}u_{0}=\frac{1}{u_{0}^{\gamma}}$ . The main technique is a generalization of the moving plane method to the Heisenberg group.

Abstract Background Congenital infection of Toxoplasma gondii is an important factor causing birth defects. The neural stem cells (NSCs) are found to be one of the target cells for the parasite during development of the brain. As a key virulence factor of the parasite that hijacks host cellular functions, ROP18 has been demonstrated to mediate the inhibition of host innate and adaptive immune responses through specific binding different host immunity related molecules. However, its pathogenic actions in NSCs remain elusive. Results In the present study, ROP18 recombinant adenovirus (Ad-ROP18) was constructed and used to infect C17.2 NSCs. After 3d- or 5d–culture in differentiation medium, the differentiation of C17.2 NSCs and the activity of the Wnt/β-catenin signaling pathway were detected. The results showed that the protein level of βIII-tubulin, a marker of neurons, in the Ad-ROP18-transfected C17.2 NSCs was significantly decreased, indicating that the differentiation of C17.2 NSCs was inhibited by the ROP18. The β-catenin level in the Ad-ROP18-transfected C17.2 NSCs was found to be lower than that in the Ad group. Also, neurogenin1 (Ngn1) and neurogenin2 (Ngn2) were downregulated significantly (P

In order to explore the knowledge base, research hotspot, development status, and future research direction of healthcare research based on information theory and complex science, a total of 3031 literature data samples from the core collection of Web of Science from 2003 to 2019 were selected for bibliometric analysis. HistCite, CiteSpace, Excel, and other analytical tools were used to deeply analyze and visualize the temporal distribution, spatial distribution, knowledge evolution, literature co-citation, and research hotspots of this field. This paper reveals the current development of healthcare research field based on information theory and science of complexity, analyzes and discusses the research hotspots and future development that trends in this field, and provides important knowledge support for researchers in this field for further relevant research.

Abstract Background Toxoplasma gondii, an obligate intracellular pathogen, has a strong affinity for the nervous system. TgCtwh3, a representative Chinese 1 Toxoplasma strain prevalent in China, has the polymorphic features of the effectors ROP16I/III with type I and GRA15II with type II Toxoplasma strains. The interaction of this atypical strain with host cells remains extremely elusive. Methods Using a transwell system, neural stem cells C17.2 were co-cultured with the tachyzoites of TgCtwh3 or standard type I RH strain. The apoptosis levels of C17.2 cells and the expression levels of related proteins in the endoplasmic reticulum stress (ERS)-mediated pathway were detected by flow cytometry and Western blotting. Results The apoptosis level of C17.2 cells co-cultured with TgCtwh3 had a significant increase compared to the negative control group; however, the apoptosis level in the TgCtwh3 group was significantly lower than that in the RH co-culture group. Western blotting analyses reveal that, after the C17.2 cells were co-cultured with TgCtwh3 and RH tachyzoites, the expression levels of caspase-12, CHOP and p-JNK in the cells increased significantly when compared to the control groups. After the pretreatment of Z-ATAD-FMK, an inhibitor of caspase-12, the apoptosis level of the C17.2 cells co-cultured with TgCtwh3 or RH tachyzoites had an apparent decline, and correspondingly, the expression levels of those related proteins were notably decreased. Conclusions Our findings suggest that TgCtwh3 may induce the apoptosis of the C17.2 cells by up-regulation of caspase-12, CHOP, and p-JNK, which are associated with ERS signaling pathways. This work contributes to better understanding the possible mechanism of brain pathology induced by T. gondii Chinese 1 isolates prevalent in China, and also reveals the potential value of ERS inhibitors to treat such related diseases in the future.

A single layer filtration system was developed to investigate the filtration and regeneration performance of diesel particle filter (DPF). The particle layer thickness was directly measured online to analyze the different filtration stages. The influence of particle property on particle layer stage performance was also investigated. The results indicate that the filtration velocity can greatly affect the deep bed filtration stage, and the deposited particle layer can be compressed even in very low filtration velocity and higher filtration velocity trends to form denser particle layer. Optimizing the pore structure can effectively shorten the deep bed filtration stage and reduce the pressure drop eventually. An empirical function was proposed to relate the pore structure and the initial increment rate of pressure drop, which presented that reducing the pore size distribution range (3σ) can result in low DPF filtration pressure drop. The filtration stage could be further divided into four stages, and the value of particle layer thickness ranging within 15~20 μm has been found to be critical number for the shift from the transient stage to the cake filtration stage. Particle with large primary diameter and BET surface was beneficial to form loose particle layer.

In this study, the regulation of abscisic acid (ABA) on cell growth and lipid biosynthesis was investigated under salt-induced stress in Chlorella pyrenoidosa. It is found that as suffering from only salt stress, although the lipid content of single cell was improved, the inhibitory effects of stress on cell proliferation was visible. When the algal cells were exposed to salt stress and ABA conditions, lipid productivity was increased (45.35 mg L-1 d-1) by 1.17-fold compared to that of control cells (20.91 mg L-1 d-1), and the inhibition to cell growth was relieved. Transcriptomic analysis revealed that after adding ABA, these genes involved in antioxidant activity, jasmonic acid (JA) biosynthesis, and lipid biosynthesis were upregulated. Subsequently, we observed that the levels of glutathione, total antioxidant capacity, trehalose, and JA were elevated and the levels of reactive oxygen species were reduced. This study presents an effective approach to improve lipid production in algal cells, a new mechanism on that ABA alleviates intracellular oxidative stress through JA signaling pathway was elaborated. [ABSTRACT FROM AUTHOR]