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Irinotecan (CPT11) chemotherapy-induced diarrhea affects a substantial cancer population due to β-glucuronidase (Gus) converting 10-O-glucuronyl-7-ethyl-10-hydroxycamptothecin (SN38G) to toxic 7-ethyl-10-hydroxycamptothecin (SN38). Existing interventions primarily address inflammation and Gus enzyme inhibition, neglecting epithelial repair and Gus-expressing bacteria. Herein, we discovered that dehydrodiisoeugenol (DDIE), isolated from nutmeg, alleviates CPT11-induced intestinal mucositis alongside a synergistic antitumor effect with CPT11 by improving weight loss, colon shortening, epithelial barrier dysfunction, goblet cells and intestinal stem cells (ISCs) loss, and wound-healing. The anti-mucositis effect of DDIE is gut microbiota-dependent. Analysis of microbiome profiling data from clinical patients and CPT11-induced mucositis mice reveals a strong correlation between CPT11 chemotoxicity and Gus-expressing bacteria, particularly Enterococcus faecalis (E. faecalis). DDIE counters CPT11-induced augmentation of E. faecalis, leading to decreased intestinal Gus and SN38 levels. The Partial Least Squares Path Model (PLS-PM) algorithm initially links E. faecalis to dysregulated epithelial renovation. This is further validated in a 3D intestinal organoid model, in which both SN38 and E. faecalis hinder the formation and differentiation of organoids. Interestingly, colonization of E. faecalis exacerbates CPT11-induced mucositis and disturbs epithelial differentiation. Our study unveils a microbiota-driven, epithelial reconstruction-mediated action of DDIE against mucositis, proposing the ‘Gus bacteria–host–irinotecan axis’ as a promising target for mitigating CPT11 chemotoxicity.

Abstract Native core microbiomes represent a unique opportunity to support food provision and plant-based industries. Yet, these microbiomes are often neglected when developing synthetic communities (SynComs) to support plant health and growth. Here, we study the contribution of native core, native non-core and non-native microorganisms to support plant production. We construct four alternative SynComs based on the excellent growth promoting ability of individual stain and paired non-antagonistic action. One of microbiome based SynCom (SC2) shows a high niche breadth and low average variation degree in-vitro interaction. The promoting-growth effect of SC2 can be transferred to non-sterile environment, attributing to the colonization of native core microorganisms and the improvement of rhizosphere promoting-growth function including nitrogen fixation, IAA production, and dissolved phosphorus. Further, microbial fertilizer based on SC2 and composite carrier (rapeseed cake fertilizer + rice husk carbon) increase the net biomass of plant by 129%. Our results highlight the fundamental importance of native core microorganisms to boost plant production.

Abstract Obesity is a global issue that warrants the identification of more effective therapeutic targets and a better understanding of the pivotal molecular pathogenesis. Annexin A1 (ANXA1) is known to inhibit phospholipase A2, exhibiting anti-inflammatory activity. However, the specific effects of ANXA1 in obesity and the underlying mechanisms of action remain unclear. Our study reveals that ANXA1 levels are elevated in the adipose tissue of individuals with obesity. Whole-body or adipocyte-specific ANXA1 deletion aggravates obesity and metabolic disorders. ANXA1 levels are higher in stromal vascular fractions (SVFs) than in mature adipocytes. Further investigation into the role of ANXA1 in SVFs reveals that ANXA1 overexpression induces lower numbers of mature adipocytes, while ANXA1-knockout SVFs exhibit the opposite effect. This suggests that ANXA1 plays an important role in adipogenesis. Mechanistically, ANXA1 competes with MYC binding protein 2 (MYCBP2) for interaction with PDZ and LIM domain 7 (PDLIM7). This exposes the MYCBP2-binding site, allowing it to bind more readily to the SMAD family member 4 (SMAD4) and promoting its ubiquitination and degradation. SMAD4 degradation downregulates peroxisome proliferator-activated receptor gamma (PPARγ) transcription and reduces adipogenesis. Treatment with Ac2-26, an active peptide derived from ANXA1, inhibits both adipogenesis and obesity through the mechanism. In conclusion, the molecular mechanism of ANXA1 inhibiting adipogenesis was first uncovered in our study, which is a potential target for obesity prevention and treatment.

The dual demands for energy saving and high-quality indoor environment present new challenge for building heating. A new evaluation index CEUC (Comprehensive Energy Utilization Coefficient) that can simultaneously evaluate the energy efficiency and thermal comfort performance is proposed in this article. CEUC is calculated using thermal comfort index PMV (Predicted Mean Vote) and PPD (Predicted Percent Dissatisfied). It takes only the heat entering human activity zone as effective utilized heat, and radiation heat is considered. Two typical heating terminals -air conditioner and floor radiant heating are selected to verify CEUC. Data show that the air supply speed of convective heating has greater impact on CEUC than that of the temperature. In practice, lower air supply temperature should be set as much as possible, and air supply angle should be less than30°. Taking CEUC as the optimization goal, the optimal wind speed for air conditioner in the room model established in this article is 4–5 m/s, and the optimal temperature for floor radiation heating is around 38 °C. The accuracy of CEUC is verified from the perspectives of energy utilization efficiency and thermal comfort.

Abstract Maturing immunometabolic research empowers immune regulation novel approaches. Progressive metabolic adaptation of tumor cells permits a thriving tumor microenvironment (TME) in which immune cells always lose the initial killing capacity, which remains an unsolved dilemma even with the development of immune checkpoint therapies. In recent years, many studies on tumor immunometabolism have been reported. The development of immunometabolism may facilitate anti-tumor immunotherapy from the recurrent crosstalk between metabolism and immunity. Here, we discuss clinical studies of the core signaling pathways of immunometabolism and their inhibitors or agonists, as well as the specific functions of these pathways in regulating immunity and metabolism, and discuss some of the identified immunometabolic checkpoints. Understanding the comprehensive advances in immunometabolism helps to revise the status quo of cancer treatment. An overview of the new landscape of immunometabolism. The PI3K pathway promotes anabolism and inhibits catabolism. The LKB1 pathway inhibits anabolism and promotes catabolism. Overactivation of PI3K/AKT/mTOR pathway and IDO, IL4I1, ACAT, Sirt2, and MTHFD2 promote immunosuppression of TME formation, as evidenced by increased Treg and decreased T-cell proliferation. The LKBI-AMPK pathway promotes the differentiation of naive T cells to effector T cells and memory T cells and promotes anti-tumor immunity in DCs.

The approach of directly combining clustering method and reinforcement learning (RL) will lead to encounter the issue where states may have different state transition processes under the same action, resulting in poor policy performance. To address this challenge with multi-dimensional continuous observation data, an improved reinforcement learning method based on unsupervised learning is proposed with a novel framework. Instead of dimensionality reduction methods, unsupervised clustering is employed to indirectly capture the underlying structure of the data. First, the proposed framework incorporates multi-dimensional information, including the current observation data, the next observation data and reward information, during the clustering process, leading to a more accurate and comprehensive low-dimensional discrete representation of the observation data while retaining preserving transition of Markov decision process. Second, by compressing the observation data into a well-defined state space, the resulting cluster labels serve as the low-dimensional discrete label-states for reinforcement learning to generate more effective and robust policies. Comparative analysis with state-of-the-art RL methods demonstrates that the improved RL methods base on framework achieves higher rewards, indicating its superior performance. Furthermore, the framework exhibits computational efficiency, as evidenced by its reasonable time complexity. This structural innovation allows for better exploration and exploitation of the transition, leading to improved policy performance in engineering applications.

This paper addresses the problem of multi-source survey data sharing in power system engineering by proposing two improved methods: a survey data sharing method combined with differential privacy and a permission change method based on attribute encryption. The survey data sharing method integrated with differential privacy achieves effective cross-professional and cross-departmental data sharing while ensuring data security by introducing multi-discriminator architecture and dynamic noise adjustment. To reduce the computational and communication overhead when user permissions change during survey data sharing, the attribute encryption-based permission change method supports dynamic changes in user permissions. The effectiveness of the proposed methods has been validated through targeted experiments in different scenarios. The work in this thesis provides a new solution for dynamic sharing of survey data in power network engineering. It contributes to the digital transformation of power network projects.

Purpose – This study aims to improve the availability of regenerative braking for urban metro vehicles by introducing a sensorless operational temperature estimation method for the braking resistor (BR) onboard the vehicle, which overcomes the vulnerability of having conventional temperature sensor. Design/methodology/approach – In this study, the energy model based sensorless estimation method is developed. By analyzing the structure and the convection dissipation process of the BR onboard the vehicle, the energy-based operational temperature model of the BR and its cooling domain is established. By adopting Newton's law of cooling and the law of conservation of energy, the energy and temperature dynamic of the BR can be stated. To minimize the use of all kinds of sensors (including both thermal and electrical), a novel regenerative braking power calculation method is proposed, which involves only the voltage of DC traction network and the duty cycle of the chopping circuit; both of them are available for the traction control unit (TCU) of the vehicle. By utilizing a real-time iterative calculation and updating the parameter of the energy model, the operational temperature of the BR can be obtained and monitored in a sensorless manner. Findings – In this study, a sensorless estimation/monitoring method of the operational temperature of BR is proposed. The results show that it is possible to utilize the existing electrical sensors that is mandatory for the traction unit’s operation to estimate the operational temperature of BR, instead of adding dedicated thermal sensors. The results also validate the effectiveness of the proposal is acceptable for the engineering practical. Originality/value – The proposal of this study provides novel concepts for the sensorless operational temperature monitoring of BR onboard rolling stocks. The proposed method only involves quasi-global electrical variable and the internal control signal within the TCU.

Abstract We previously reported initial clinical results of post-transcriptional gene silencing of BCL11A expression (NCT 03282656) reversing the fetal to adult hemoglobin switch. A goal of this approach is to increase fetal hemoglobin (HbF) expression while coordinately reducing sickle hemoglobin (HbS) expression. The resulting combinatorial effect should prove effective in inhibiting HbS polymerization at lower physiologic oxygen values thereby mitigating disease complications. Here we report results of exploratory single-cell analysis of patients in which BCL11A is targeted molecularly and compare results with cells of patients treated with hydroxyurea (HU), the current standard of care. We use single-cell assays to assess HbF, HbS, oxygen saturation, and hemoglobin polymer content in RBCs for nine gene therapy trial subjects (BCLshmiR, median HbF% = 27.9) and compare them to 10 HU-treated subjects demonstrating high and comparable levels of HbF (HU High Responders, median HbF% = 27.0). All BCL11A patients achieved the primary endpoint for NCT 03282656, which was defined by an absolute neutrophil count greater than or equal to 0.5 × 109 cells/L for three consecutive days, achieved within 7 weeks following infusion. Flow cytometric assessment of single-RBC HbF and HbS shows fewer RBCs with high HbS% that would be most susceptible to sickling in BCLshmiR vs. HU High Responders: median 42% of RBCs with HbS%>70% in BCLshmiR vs. 61% in HU High Responders (p = 0.004). BCLshmiR subjects also demonstrate more RBCs resistant to HbS polymerization at lower physiologic oxygen tension: median 32% vs. 25% in HU High Responders (p = 0.006). Gene therapy-induced BCL11A down-regulation reverses the fetal-to-adult hemoglobin switch and induces RBCs with higher HbF%, lower HbS%, and greater resistance to deoxygenation-induced polymerization in clinical trial subjects compared with a cohort of highly responsive hydroxyurea-treated subjects.

Contrast-induced acute kidney injury (CI-AKI) is a growingly common kidney problem caused by medical procedures involving contrast media (CM), especially in older patients with existing health issues. It is crucial to pinpoint potential biomarkers for the early detection of CI-AKI. Previously, we observed that iodixanol affects glucose, choline, and glutathione metabolism in endothelial cells under laboratory conditions. In this study, we used 1H NMR-based metabolomics to examine the metabolic changes in the blood plasma of elderly patients with cardiovascular disease (CVD) before and after receiving iodixanol. We identified altered metabolites in plasma 24 and 48 h after iodixanol injection compared to levels before injection. Notably, metabolites such as glucose, unsaturated fatty acids (UFA), low-density lipoprotein (LDL)/very low-density lipoprotein (VLDL), pyruvate, choline, and glycine showed potential as biomarkers at 24 h post-injection compared to levels before injection. Similarly, glucose, pyruvate, lactate, choline, and glycine in plasma could serve as potential biomarkers at 48 h post-injection. Iodixanol notably affected pathways related to glycolysis, fatty acid breakdown, and amino acid metabolism according to our metabolic pathway analysis. The altered levels of specific metabolites in plasma could be indicative of CM-induced kidney injury. Overall, this research aids in understanding the physiological mechanisms involved and in identifying early biomarkers and prevention strategies for CI-AKI.

Abstract Background The TNM staging system cannot accurately predict the prognosis of postoperative gastric signet ring cell carcinoma (GSRC) given its unique biological behavior, epidemiological features, and various prognostic factors. Therefore, a reliable postoperative prognostic evaluation system for GSRC is required. This study aimed to establish a nomogram to predict the overall survival (OS) rate of postoperative patients with GSRC and validate it in the real world. Methods Clinical data of postoperative patients with GSRC from 2002 to 2014 were collected from the Surveillance, Epidemiology, and End Results database and randomly assigned to training and internal validation sets at a 7:3 ratio. The external validation set used data from 124 postoperative patients with GSRC who were admitted to the Affiliated Tumor Hospital of Harbin Medical University between 2002 and 2014. The independent risk factors affecting OS were screened using univariate and multivariate analyses to construct a nomogram. The performance of the model was evaluated using the C-index, receiver operating characteristic curve (ROC), calibration curve, decision analysis (DCA) curve, and adjuvant chemotherapy decision analysis. Results Univariate/multivariate analysis indicated that age, stage, T, M, regional nodes optimized (RNE), and lymph node metastasis rate (LNMR) were independent risk factors affecting prognosis. The C-indices of the training, internal validation, and external validation sets are 0.741, 0.741, and 0.786, respectively. The ROC curves for the first, third, and fifth years in three sets had higher areas under the curves, (training set, 0.782, 0.864, 0.883; internal validation set, 0.781, 0.863, 0.877; external validation set, 0.819, 0.863, 0.835). The calibration curve showed high consistency between the nomogram-predicted 1-, 3-, and 5-year OS and the actual OS in the three queues. The DCA curve indicated that applying the nomogram enhanced the net clinical benefits. The nomogram effectively distinguished patients in each subgroup into high- and low-risk groups. Adjuvant chemotherapy can significantly improve OS in high-risk group (P = 0.034), while the presence or absence of adjuvant chemotherapy in low-risk group has no significant impact on OS (P = 0.192). Conclusions The nomogram can effectively predict the OS of patients with GSRC and may help doctors make personalized prognostic judgments and clinical treatment decisions.

Abstract Purpose The present study aimed to explore the anticancer activity of hirsuteine (HST), an indole alkaloid from the traditional Chinese herbal medicine Uncaria rhynchophylla, against colorectal cancer (CRC) and the underlining mechanism. Methods MTT, colony formation, flow cytometry and MDC staining were conducted to confirm the antiproliferative effect of HST on human CRC cells harboring different p53 status. Protein expressions were evaluated by the Western blot analysis. p53 protein half-life and the interaction between p53 and MDM2 were investigated using cycloheximide (CHX)-chase assay and Co-immunoprecipitation (Co-IP), respectively. Transcriptional activity of p53 was examined by qRT-PCR and Chromatin immunoprecipitation (ChIP). Xenograft tumor in nude mice was created to evaluate in vivo anticancer effect of HST against CRC. Results HST inhibited cell growth, arrested cell cycle and induced autophagy, showing efficient anticancer effects on CRC cells independent of p53 status. In HCT-8 cells, HST prolonged wtp53 half-life, and upregulated mRNA level of p21, suggesting that HST activated the p53 pathway through enhancement of wtp53 stability and transcriptional activity. Meanwhile in SW620 cells, HST induced MDM2-mediated proteasomal degradation of mutp53R273H, increased the DNA-binding ability of mutp53R273H at the p21 promoter, and upregulated mRNA levels of p21 and MDM2, demonstrating the depletion of mutp53R273H and restoration of its wild-type-like properties by HST. p53 knockdown by siRNA significantly impaired the growth inhibition of HST on HCT-8 and SW620 cells. Moreover, HST showed anticancer effects in xenograft tumors, accompanied with an opposite regulation of wtp53 and mutp53 R273H in mechanism. Conclusion This study revealed the anticancer efficacy of HST against CRC via opposite modulation of wtp53 and mutp53 R273H, indicating the potential of HST to be a CRC drug candidate targeting p53 signaling.

The rice production system in China is facing challenges, including declining soil fertility and a stagnant rice yield. This study aimed to test whether integrating the return of straw to fields with less power puddling could simultaneously enhance soil fertility and rice yields. Therefore, field experiments were conducted in Heilongjiang Province, a key rice-growing region in China, from 2017 to 2021, using three different planting methods: control group (CK), straw return (SR) and straw return integrated with less power puddling (SR + LP). The results showed that small soil aggregates (particle diameter < 0.25 mm) and soil bulk density were significantly decreased when straw return was integrated with less power puddling. These changes contributed to the preservation of soil structure. Simultaneously, this approach significantly increased soil ammonium nitrogen content from 9.9 to 10.9 mg kg−1, organic matter content from 35.0 to 36.2 g kg−1, available nitrogen content from 140.5 to 147.0 mg kg−1 and available potassium content from 128.6 to 136.8 mg kg−1 at mature stage on average. Consequently, the post-heading stored assimilates accumulation of rice was increased from 6.12 to 6.43 t ha−1, and the nitrogen, phosphorus and potassium accumulation of rice were increased by 7.85 kg ha−1, 1.13 kg ha−1 and 5.68 kg ha−1, respectively. These changes ultimately resulted in a higher 1000 g weight and filled grain rate, providing the foundation for higher yields (an increase from 9.31 t ha−1 to 9.55 t ha−1). Furthermore, this approach also increased the net income for farmers by USD 14 t ha−1. In summary, this study demonstrates that integrating straw return with less power puddling can enhance soil’s nutrient supply and retention capacity. This enhancement may boost the absorption and transportation of nutrients, ultimately establishing the groundwork for higher yields and economic benefits by enhancing the 1000 g weight and filled grain rate. Future research should delve deeper into its applicability across different ecosystems and investigate the yield-increasing mechanisms.

ABSTRACT Avibacterium paragallinarum is the pathogen involved in infectious coryza (IC), an acute infectious upper respiratory disease in chickens. The prevalence of IC has increased in China in recent years. There is a lack of reliable and effective procedures for gene manipulation, which has limited the research on the bacterial genetics and pathogenesis of A. paragallinarum. Natural transformation has been developed as a method of gene manipulation in Pasteurellaceae by the introduction of foreign genes or DNA fragments into bacterial cells, but there has been no report on natural transformation in A. paragallinarum. In this study, we analyzed the existence of homologous genetic factors and competence proteins underlying natural transformation in A. paragallinarum and established a method for transformation in it. Through bioinformatics analysis, we identified 16 homologs of Haemophilus influenzae competence proteins in A. paragallinarum. We found that the uptake signal sequence (USS) was overrepresented in the genome of A. paragallinarum (1,537 to 1,641 copies of the core sequence ACCGCACTT). We then constructed a plasmid, pEA-KU, that carries the USS and a plasmid, pEA-K, without the USS. These plasmids can be transferred via natural transformation into naturally competent strains of A. paragallinarum. Significantly, the plasmid that carries USS showed a higher transformation efficiency. In summary, our results demonstrate that A. paragallinarum has the ability to undergo natural transformation. These findings should prove to be a valuable tool for gene manipulation in A. paragallinarum. IMPORTANCE Natural transformation is an important mechanism for bacteria to acquire exogenous DNA molecules during the process of evolution. Additionally, it can also be used as a method to introduce foreign genes into bacteria under laboratory conditions. Natural transformation does not require equipment such as an electroporation apparatus. It is easy to perform and is similar to gene transfer under natural conditions. However, there have been no reports on natural transformation in Avibacterium paragallinarum. In this study, we analyzed the presence of homologous genetic factors and competence proteins underlying natural transformation in A. paragallinarum. Our results indicate that natural competence could be induced in A. paragallinarum serovars A, B, and C. Furthermore, the method that we established to transform plasmids into naturally competent A. paragallinarum strains was stable and efficient.

To improve the performance of anti-jamming communication in dynamic and adversarial jamming environment, an improved anti-jamming method is proposed based on deep reinforcement learning and feature engineering. Different from the existing studies that use computer vision of deep learning based on the infinite state of spectrum waterfall, the proposed method relays on analyzing spectrum differences between adjacent time slots which contains information and features of jamming patterns. First, anti-jamming strategy is trained by countering the jammer which carries out a random jamming patterns switching strategy. Second, an improved state space is introduced by containing historical spectrum of communication and jamming signal between adjacent time slots, which can help an anti-jamming agent effectively extract the features of jamming patterns to reduce computational complexity. In addition, an improved reward function based on channel switch cost is improved for considering propagation characteristics which may cause communication performance lost. Taking advantage of both feature engineering and deep reinforcement learning, an improved anti-jamming method is proposed to improve reliable anti-jamming performance. Compared with the traditional CNN-based deep reinforcement learning anti-jamming method, simulation results show that the improved method can obtain better performance and lower computational complexity.

Abstract Industrial parks contribute greatly to China’s economic development while emitting huge air pollutants. It is necessary to study the characteristics of air pollutant emissions in industrial parks. In this study, emission inventories for 11 industrial parks were established. Meanwhile, the source emission and spatial distribution characteristics of the industrial park were analyzed. The cluster analysis was used to classify these parks into “4Hs”, “Mixed” and “4Ls” parks. “4Hs”, “Mixed” and “4Ls” represent that the levels of energy intensity, economic proportion of energy-intensive industries, coal proportion and pollution performance value are high, medium and low in turn. Then three emission reduction measures were set up to estimate the emission reduction potential and environmental impacts. The results show that: (1) the emissions of SO2, NOx, CO, PM10, PM2.5, VOCs and NH3 of 11 industrial parks in 2017 were 11.2, 23.1, 30.8, 8.3, 3.5, 5.1, and 1.1 kt, respectively. (2) Power plants were the largest source of SO2 and NOx emissions, and industrial processes were the largest emission source of CO, PM10, PM2.5, VOCs and NH3. (3) “4Hs” parks with traditional energy-intensive industries as the leading industries should be the emphasis of air pollutant emission reduction. (4) Through the optimal emission reduction measures, SO2, NOx, PM10, PM2.5 and VOCs were reduced by 81, 46, 51, 46 and 77%, respectively. Environmental impact reductions include 1.6 kt SO2eq acidified gas emissions, 1.4 kt PO4 3−eq eutrophication substances, 4.2 kt PM10eq atmospheric particulate emissions, 7.0 kt 1,4-DCEeq human toxic substances, and 5.2 kt PM2.5 eq breathing Inorganic. This study is helpful to understand the characteristics of air pollutants emissions in industrial parks and promotes the proposal and implementation of air pollutant emissions reduction strategies.

Purpose: Osteoarthritis (OA) is a common degenerative disease, which still lacks specific therapeutic drugs. Synovitis is one of the most important pathological process in OA. Therefore, we aim to identify and analyze the hub genes and their related networks of OA synovium with bioinformatics tools to provide theoretical basis for potential drugs.Materials and methods: Two datasets were obtained from GEO. DEGs and hub genes of OA synovial tissue were screened through Gene Ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment as well as protein—protein interaction (PPI) network analysis. Subsequently, the correlation between expression of hub genes and ferroptosis or pyroptosis was analyzed. CeRNA regulatory network was constructed after predicting the upstream miRNAs and lncRNAs. The validation of hub genes was undertook through RT-qPCR and ELISA. Finally, potential drugs targeting pathways and hub genes were identified, followed by the validation of the effect of two potential drugs on OA.Results: A total of 161 commom DEGs were obtained, of which 8 genes were finally identified as hub genes through GO and KEGG enrichment analysis as well as PPI network analysis. Eight genes related to ferroptosis and pyroptosis respectively were significantly correlated to the expression of hub genes. 24 miRNAs and 69 lncRNAs were identified to construct the ceRNA regulatory network. The validation of EGR1, JUN, MYC, FOSL1, and FOSL2 met the trend of bioinformatics analysis. Etanercept and Iguratimod reduced the secretion of MMP-13 and ADAMTS5 of fibroblast-like synoviocyte.Conclusion: EGR1, JUN, MYC, FOSL1, and FOSL2 were identified as hub genes in the development of OA after series of bioinformatics analysis and validation. Etanercept and Iguratimod seemed to have opportunities to be novel drugs for OA.

Abstract Chlamydia spp. are prevalent zoonotic pathogens that infect a wide variety of host species. Chlamydia abortus (C. abortus) infection in yaks has been reported in Gansu and Qinghai province, China. However, no data about C. abortus infection are available in yaks in Tibet, China. A total of 938 serum samples was collected from yaks in Tibet, China and specific antibodies against C. abortus were detected by the enzyme-linked immunosorbent assay (ELISA). The results showed that the overall seroprevalence of C. abortus in yaks was 104/938 (11.1 %, 95 % confidence interval [CI] 9.1–13.1). The prevalence in female and male yaks was 59/556 (10.6 %, 95 % CI 8.0-13.2) and 45/382 (11.8 %, 95 % CI 8.5–15.0), respectively with no significant difference (p > 0.05). The seroprevalence of antibodies to C. abortus in yaks ranged from 8.0 to 18.2 % among the six different areas, and the difference was also without statistical significance (p > 0.05). The prevalence among different age groups ranged from 7.0 to 15.9 %, with a higher prevalence among 1 to 2 years age category. The results demonstrate the presence of C. abortus infection in yaks in Tibet and may pose a risk for the general yak populations in addition to its potential impact on public health and the local Tibetan economy. To our knowledge, this is the first seroprevalence survey of C. abortus in yaks in Tibet, China.

Mixed-matrix membranes (MMMs) have received much attention due to their processable advantages of polymer and high permeability and/or selectivity of porous metal-organic frameworks (MOFs) fillers. However, the interfacial defects caused by poor interaction between MOFs with polymers and the agglomeration phenomenon caused by uneven dispersion of MOFs are common problems in mixed-matrix membranes. Currently, the priming protocol is one of solutions to the above problems, but it cannot precisely regulate the dispersion of particles and the interfacial compatibility between two phases. Herein, covalent grafting of polyimide 6FDA-Durene onto the surface of UiO-66-NH2 can mitigate the aggregation of fillers inside the polymeric matrices and improve the interfacial interaction between two phases, thus significantly improving the CO2/CH4 separation performance on the as-synthesized MMMs. The explored gas transport mechanism indicated that the improved separation was due to the raise of solubility selectivity. Furthermore, the stronger covalent bond between fillers and polyimide than physical interaction of priming protocol also endows the improved anti-plasticization phenomenon for CO2/CH4 separation.

PurposeRecently, long noncoding RNA LINC01134 has been shown to reduce cell viability and apoptosis via the antioxidant stress pathway, thereby enhancing OXA resistance in hepatocellular carcinoma. However, the association of LINC01134 with ferroptosis and the underlying molecular mechanisms remain to be elucidated.MethodsBioinformatics analysis was employed to screen lncRNAs positively correlated with GPX4 and poor clinical prognosis. And Western blot and RT-PCR analysis in HCC cells confirmed the effect of LINC01134 on GPX4 expression. In addition, LINC01134 siRNA was transfected in HCC cells to detect the changes in cell viability, ROS, lipid peroxidation, MDA levels and GSH/GSSG levels. CCK-8, colony formation and apoptosis assays were performed to determine the effect of LINC01134 on cell death. The effect of LINC01134 and OXA on Nrf2 transcriptional binding to GPX4 was analyzed using dual luciferase reporter assay and CHIP. The expression of GPX4 and Nrf2 in HCC tissues was detected by FISH and IHC.ResultsLINC01134 is a novel lncRNA positively correlated with GPx4 and associated with poor clinical prognosis. Silenced LINC01134 conferred OXA sensitivity by enhancing total ROS, lipid ROS, MDA levels and decreasing GSH/GSSG ratio. Mechanistically, LINC01134 and OXA could promote Nrf2 recruitment to the GPX4 promoter region to exert transcriptional regulation of GPX4. Clinically, LINC01134 was positively correlated with GPX4 or Nrf2, demonstrating the clinical significance of LINC01134, Nrf2 and GPX4 in OXA resistance of HCC.ConclusionsWe identified LINC01134/Nrf2/GPX4 as a novel and critical axis to regulate HCC growth and progression. Targeting GPX4, knocking down LINC01134 or Nrf2 could be a potential therapeutic strategy for HCC.

Riemerella anatipestifer (R. anatipestifer) is a multidrug-resistant bacterium and an important pathogen responsible for major economic losses in the duck industry. Our previous study revealed that the efflux pump is an important resistance mechanism of R. anatipestifer. Bioinformatics analysis indicated that the GE296_RS02355 gene (denoted here as RanQ), a putative small multidrug resistance (SMR)-type efflux pump, is highly conserved in R. anatipestifer strains and important for the multidrug resistance. In the present study, we characterized the GE296_RS02355 gene in R. anatipestifer strain LZ-01. First, the deletion strain RA-LZ01ΔGE296_RS02355 and complemented strain RA-LZ01cΔGE296_RS02355 were constructed. When compared with that of the wild-type (WT) strain RA-LZ01, the mutant strain ΔRanQ showed no significant influence on bacterial growth, virulence, invasion and adhesion, morphology biofilm formation ability, and glucose metabolism. In addition, the ΔRanQ mutant strain did not alter the drug resistance phenotype of the WT strain RA-LZ01 and displayed enhanced sensitivity toward structurally related quaternary ammonium compounds, such as benzalkonium chloride and methyl viologen, which show high efflux specificity and selectivity. This study may help elucidate the unprecedented biological functions of the SMR-type efflux pump in R. anatipestifer. Thus, if this determinant is horizontally transferred, it could cause the spread of quaternary ammonium compound resistance among bacterial species.

As two commonly used fungicides, carbendazim and tebuconazole are widely found in the environment and in foods. Studies have reported that these fungicides can induce hepatic oxidative stress and other health risks. Nevertheless, the influences of exposure to carbendazim and tebuconazole at their acceptable daily intake (ADI) doses on hepatic oxidative stress, and the residual distributions in mice remain unclear. To fill these gaps, ICR (CD-1) mice were exposed to carbendazim and tebuconazole at their ADI doses by oral administration for 4 weeks in this study. The results showed that tebuconazole accumulated primarily in the epididymal fat of mice (16.84 μg/kg), whereas no significant residues of carbendazim in the tissues were observed. In addition, exposure to ADI doses of tebuconazole significantly reduced liver coefficients and induced hepatic oxidative stress in mice, including elevating the levels of glutathione and malonaldehyde. However, no significant impacts were observed on the hepatic redox homeostasis in mice after exposure to carbendazim at its ADI dose. The results could be helpful for understanding the exposure risks of carbendazim and tebuconazole in terms of low doses and long term.

ABSTRACT: Infectious coryza (IC) is an acute infectious upper respiratory disease in chickens. Recently, the prevalence of IC has increased in China. In this study, to clarify the pathogenic mechanism and innate immune response of Avibacterium paragallinarum (A. paragallinarum), an infection experiment with A. paragallinarum was conducted. Our results showed that the whole course of IC was approximately 7 d. The clinical signs score was highest at 3 dpi and decreased from 5 dpi. A large amount of mucus and exudates was found in the infraorbital sinuses and nasal cavity. The A. paragallinarum contents in blood remained the highest, reaching 9.16 × 105 CFU/g at 5 dpi, which indicated that A. paragallinarum could rapidly invade the host, replicate in the blood and cause bacteremia. A. paragallinarum targets the upper respiratory tract. The infiltration of inflammatory cells, macrophages, and heterophilic granulocytes was only observed in the nasal cavity and infraorbital sinus. The Tlr4 and Nod1 pathways were activated and induced proinflammatory responses in chickens after infection with A. paragallinarum. The expression of Il1β and Il6 in the nasal cavity was significantly higher than that in the spleen, and it was consistent with the gross lesions and pathological changes. In particular, the expression of Il6 increased 229.07-fold at 1 dpi in the nasal cavity and increased 3.12-fold in the spleen. The high level of proinflammatory cytokines in the nasal cavity at an early stage of infection may be the main factor related to acute upper respiratory inflammation in chickens. These findings provide a reference for the occurrence and development of diseases mediated by A. paragallinarum.

There is no doubt that antimicrobial resistance (AMR) is a global threat to public health and safety, regardless of whether it’s caused by people or natural transmission. This study aimed to investigate the genetic characteristics and variations of tigecycline-resistant Gram-negative isolates from herbivores in northwest China. In this study, a total of 300 samples were collected from various provinces in northwest China, and 11 strains (3.67%) of tigecycline-resistant bacteria were obtained. In addition, bacterial identification and antibiotic susceptibility testing against 14 antibiotics were performed. All isolates were multiple drug-resistant (MDR) and resistant to more than three kinds of antibiotics. Using an Illumina MiSeq platform, 11 tigecycline-resistant isolates were sequenced using whole genome sequencing (WGS). The assembled draft genomes were annotated, and then sequences were blasted against the AMR gene database and virulence factor database. Several resistance genes mediating drug resistance were detected by WGS, including fluoroquinolone resistance genes (gyrA_S83L, gyrA_D87N, S83L, parC_S80I, and gyrB_S463A), fosfomycin resistance genes (GlpT_E448K and UhpT_E350Q), beta-lactam resistance genes (FtsI_D350N and S357N), and the tigecycline resistance gene (tetR N/A). Furthermore, there were five kinds of chromosomally encoded genetic systems that confer MDR (MarR_Y137H, G103S, MarR_N/A, SoxR_N/A, SoxS_N/A, AcrR N/A, and MexZ_K127E). A comprehensive analysis of MDR strains derived from WGS was used to detect variable antimicrobial resistance genes and their precise mechanisms of resistance. In addition, we found a novel ST type of Escherichia coli (ST13667) and a newly discovered point mutation (K127E) in the MexZ gene of Pseudomonas aeruginosa. WGS plays a crucial role in AMR control, prevention strategies, as well as multifaceted intervention strategies.

Background: The management of gastric cancer (GC) still lacks tumor markers with high specificity and sensitivity. The goal of current research is to find effective diagnostic and prognostic markers and to clarify their related mechanisms.Methods: In this study, we integrated GC DNA methylation data from publicly available datasets obtained from TCGA and GEO databases, and applied random forest and LASSO analysis methods to screen reliable differential methylation sites (DMSs) for GC diagnosis. We constructed a diagnostic model of GC by logistic analysis and conducted verification and clinical correlation analysis. We screened credible prognostic DMSs through univariate Cox and LASSO analyses and verified a prognostic model of GC by multivariate Cox analysis. Independent prognostic and biological function analyses were performed for the prognostic risk score. We performed TP53 correlation analysis, mutation and prognosis analysis on eleven-DNA methylation driver gene (DMG), and constructed a multifactor regulatory network of key genes.Results: The five-DMS diagnostic model distinguished GC from normal samples, and diagnostic risk value was significantly correlated with grade and tumor location. The prediction accuracy of the eleven-DMS prognostic model was verified in both the training and validation datasets, indicating its certain potential for GC survival prediction. The survival rate of the high-risk group was significantly lower than that of the low-risk group. The prognostic risk score was an independent risk factor for the prognosis of GC, which was significantly correlated with N stage and tumor location, positively correlated with the VIM gene, and negatively correlated with the CDH1 gene. The expression of CHRNB2 decreased significantly in the TP53 mutation group of gastric cancer patients, and there were significant differences in CCDC69, RASSF2, CHRNB2, ARMC9, and RPN1 between the TP53 mutation group and the TP53 non-mutation group of gastric cancer patients. In addition, CEP290, UBXN8, KDM4A, RPN1 had high frequency mutations and the function of eleven-DMG mutation related genes in GC patients is widely enriched in multiple pathways.Conclusion: Combined, the five-DMS diagnostic and eleven-DMS prognostic GC models are important tools for accurate and individualized treatment. The study provides direction for exploring potential markers of GC.

In order to improve the flight quality of UAV, study the hardware-in-the-loop simulation application of UAV control, and form a set of universal UAV flight control law design and hardware-in-the-loop simulation method, the Z-shaped aircraft with complex aerodynamic characteristics is studied. The Z-shaped aircraft can be folded in the direction of the fuselage for easy storage and transportation. According to the shape parameters of Z-shaped aircraft, the aerodynamic data are obtained. On this basis, the longitudinal linear model is established by using the principle of small disturbance linearization. The longitudinal static stability of the model is studied by adding disturbance pulses. The transfer function of each link is selected, the pitch control loop is established, the PID parameters are adjusted, the longitudinal control law is designed, and simulation is conducted by using Simulink and hardware-in-the-loop simulator. The simulation results show that UAV has good static stability, reasonable selection of PID control parameters, small system overshoot and short adjustment time, which can improve the flight quality of UAV. Hardware-in-the-loop simulation can more truly and intuitively reflect the advantages of UAV attitude. The modeling and simulation methods have certain universality and can be applied to other fixed-wing UAVs.

After application, pesticides remained in the field may contaminate water resources through surface runoff and leaching, posing a threat to aquatic ecosystem. In the current study, the accumulation, translocation, distribution and removal of four triazine pesticides (simazine, atrazine, terbuthylazine and metribuzin) by free floating aquatic plant Eichhornia crassipes (E. crassipes) in water-sediment microcosm were investigated and the removal mechanisms were explored. E. crassipes was exposed to an initial concentration of 50 μg·L−1 and the pesticide levels in water, sediment, roots and shoots of E. crassipes were monitored during 30 days. The results demonstrated that E. crassipes was capable of accumulating triazine pesticides with the bio-concentration factor (BCF) ranging from 0.8 to 18.4. Triazine pesticides were mainly stored in roots, and root accumulation and translocation amount depend on the hydrophobicity of the pesticides. The removal of the pesticides in water were significantly accelerated by the presence of E. crassipes, with the removal efficiency ranging from 66% to 79% after 30 days of treatment. Though phytoaccumulation only constituted 2–18% of the total spiked pesticides in the microcosm, E. crassipes played a vital role in removing simazine, atrazine and metribuzin. However, microbial degradation in sediment was the main pathway for the removal of terbuthylazine in the microcosm. This study demonstrated the potential application of E. crassipes to accelerate removal of contaminants from aquatic environment.

To mitigate environmental pressure, many studies have calculated the CO2 emissions of a sector from the perspectives of production and consumption. However, determining a sector's CO2 reduction tasks based on these two indicators may underestimate the contribution of that sector to CO2 reductions in the entire economic system. The total CO2 emission reduction in the entire economic system cannot be regarded as a simple sum of CO2 emission reductions in various sectors. The situation that the reduction of CO2 emissions in one sector can promote the reduction of CO2 emissions in other sectors through a series of chain reactions in the industrial chain needs to be considered. Therefore, the purpose of this paper is to develop new indicators to assess the impact of sectoral CO2 reduction in the industrial chain, that is, when CO2 emissions are reduced in one sector, how much it promotes to the reductions in other sectors. We take China as a case and gain additional insights that are not available from existing indicators. The results reveal when the CO2 emissions of the Electricity and hot water production and supply sector change by 10%, its PCIC-CE and CCIC-CE are 4.13% and 3.83%, respectively. This indicate that the direct reduction of CO2 emissions in the sector has an additional impact on the CO2 emissions of the entire economic system. Hence, the new environmental indicators proposed in this paper can complement the existing indicators and guide sector-level environmental pressure mitigation strategies from a holistic perspective.

BackgroundThe SET and MYND domain-containing (SMYD) gene family comprises a set of genes encoding lysine methyltransferases. This study aimed to clarify the relationship between the expression levels of SMYD family members and the prognosis and immune infiltration of malignant tumors of the digestive system.MethodsThe Oncomine, Ualcan, Kaplan–Meier Plotter, cBioPortal, Metascape, and TIMER databases and tools were used to analyze the correlation of SMYD family mRNA expression, clinical stage, TP53 mutation status, prognostic value, gene mutation, and immune infiltration in patients with esophageal carcinoma (ESCA), liver hepatocellular carcinoma (LIHC), and stomach adenocarcinoma (STAD).ResultsIn ESCA, the mRNA expression of SMYD2/3/4/5 was significantly correlated with the incidence rate, that of SMYD2/3 with the clinical stage, that of SMYD2/3/4/5 with TP53 mutation status, that of SMYD2/4/5 with overall survival (OS), and that of SMYD1/2/3/4 with relapse-free survival (RFS). In LIHC, the mRNA expression of SMYD1/2/3/4/5 was significantly correlated with the incidence rate, that of SMYD2/4/5 with the clinical stage, that of SMYD3/5 with TP53 mutation status, that of SMYD2/3/4/5 with OS, and that of SMYD3/5 with RFS. In STAD, the mRNA expression of SMYD2/3/4/5 was significantly correlated with the incidence rate, that of SMYD1/4 with the clinical stage, that of SMYD1/2/3/5 with TP53 mutation status, that of SMYD1/3/4 with OS, and that of SMYD1/3 with RFS. Furthermore, the function of SMYD family mutation-related genes in ESCA, LIHC, and STAD patients was mainly related to pathways, such as mitochondrial gene expression, mitochondrial matrix, and mitochondrial translation. The expression of SMYD family genes was significantly correlated with the infiltration of six immune cell types and eight types of immune check sites.ConclusionSMYD family genes are differentially expressed and frequently mutated in malignant tumors of the digestive system (ESCA, LIHC, and gastric cancer). They are potential markers for prognostic prediction and have important significance in immunity and targeted therapy.

Magnesium (Mg) plays a crucial role in rice yield. Heilongjiang Province is the main rice-producing region of China, playing an important role in guaranteeing China's and the world's grain security. However, rarely Mg fertilization is applied in this province. Soil Mg status of main rice-producing areas in Heilongjiang Province was investigated and Mg fertilizer experiments were conducted aiming to provide fertilizer recommendation in this region. A total of 358 soil samples from the 0–20 cm and 20–40 cm soil layer from the main rice-producing areas of Heilongjiang Province were collected to analyze soil exchangeable Mg (ex-Mg) and relative chemical properties. Meanwhile, field experiments of soil and foliar Mg application were performed in 2017–2019 to identify the effect of this nutrient on rice yield. The results showed that the ex-Mg concentration in the 0–20 cm and 20–40 cm soil layer was 282 mg kg−1 and 243 mg kg−1, respectively. Moreover, ex-Mg ranged on the abundant and exceptionally abundant level accounted for 75% in 0–20 cm and 55.3% in 20–40 cm. The ex-Mg concentration in the upper soil layer was higher than in the lower soil layer and varied depending on regions, which the west part of Heilongjiang Province showed the highest concentration in both soil layers. Correlation analysis showed that there had a significant (P < 0.05) linear relationship between ex-Mg and pH, CEC, ex-K, Ca, K/Mg, and Ca/Mg. Meanwhile, the results of path coefficients demonstrated that pH, CEC, and Ca/Mg had the most direct effect on ex-Mg concentration among these above factors. Soil Mg application had little effect on rice yield, which might be related to the soil Mg concentration and availability, and root uptake activity. Foliar Mg application increased rice yield by 8.45% (P < 0.05) compared to without Mg treatment, increased 1,000-grain weight by 2.62% (P < 0.05), and spikelet number per panicle by 4.19% (P < 0.05). In general, the paddy soil ex-Mg concentration in Heilongjiang Province was abundant. Soil-applied Mg played little role in rice yield in ex-Mg abundant regions, while foliar application increased rice yields significantly via increasing 1,000-grain weight and spikelet number per panicle.

Monomeric C-reactive protein (mCRP) is now accepted as having a key role in modulating inflammation and in particular, has been strongly associated with atherosclerotic arterial plaque progression and instability and neuroinflammation after stroke where a build-up of the mCRP protein within the brain parenchyma appears to be connected to vascular damage, neurodegenerative pathophysiology and possibly Alzheimer's Disease (AD) and dementia. Here, using immunohistochemical analysis, we wanted to confirm mCRP localization and overall distribution within a cohort of AD patients showing evidence of previous infarction and then focus on its co-localization with inflammatory active regions in order to provide further evidence of its functional and direct impact. We showed that mCRP was particularly seen in large amounts within brain vessels of all sizes and that the immediate micro-environment surrounding these had become laden with mCRP positive cells and extra cellular matrix. This suggested possible leakage and transport into the local tissue. The mCRP-positive regions were almost always associated with neurodegenerative, damaged tissue as hallmarked by co-positivity with pTau and β-amyloid staining. Where this occurred, cells with the morphology of neurons, macrophages and glia, as well as smaller microvessels became mCRP-positive in regions staining for the inflammatory markers CD68 (macrophage), interleukin-1 beta (IL-1β) and nuclear factor kappa B (NFκB), showing evidence of a perpetuation of inflammation. Positive staining for mCRP was seen even in distant hypothalamic regions. In conclusion, brain injury or inflammatory neurodegenerative processes are strongly associated with mCRP localization within the tissue and given our knowledge of its biological properties, it is likely that this protein plays a direct role in promoting tissue damage and supporting progression of AD after injury.

Infectious coryza (IC) is an acute respiratory disease caused by Avibacterium paragallinarum (Av. paragallinarum). In recent years, there have been frequent outbreaks of IC in chickens vaccinated with an inactivated vaccine, causing huge losses to the poultry industry. In this study, the protective efficacy of the trivalent inactivated IC vaccine (PT Medion Farma Jaya) against the field isolates of three serovars of Av. paragallinarum was verified. After vaccination, the hemagglutination inhibition antibody titers in double-vaccinated groups (A2, B2, and C2) were higher than those in single-vaccinated groups (A1, B1, and C1). The highest antibody titer was 213.1 at 3 weeks after the booster vaccination in group A2. Consistent with the trend in hemagglutination inhibition antibody titers, the protective efficacy of double vaccination was better than that of single vaccination. The clinical symptoms and pathological changes were alleviated, or the bacterial shedding was significantly reduced with double vaccination after challenge with field isolates of three serovars (p < 0.05). In particular, the chickens with double vaccination showed no clinical symptoms, pathological changes, or bacterial shedding after challenge by the serovar C strain. There was no significant difference in body weight and egg production between the double-vaccinated groups and the negative control group (p > 0.05). Therefore, we recommend that the commercial IC vaccine should be double-vaccinated in clinical applications.

Endothelial dysfunction is involved in the pathophysiological processes of contrast media (CM)–induced acute kidney injury (CI-AKI) after vascular angiography or intervention. Previous study found that apolipoprotein A-I (apoA-I) mimetic peptide, D-4F, alleviates endothelial impairments via upregulating heme oxygenase-1 (HO-1) expression and scavenging excessively generated reactive oxygen species (ROS). However, whether D-4F could ameliorate oxidative injuries in endothelial cells through suppressing ROS production remains unclear. In this study, a representative nonionic iodinated CM, iodixanol, was chosen for the in vitro and in vivo studies. Endothelial cell viability was assayed using micrographs, lactate dehydrogenase (LDH) activity, and cell counting kit-8 (CCK-8). Apoptosis was detected using flow cytometry analysis and caspase-3 activation. Endothelial inflammation was tested using monocyte adhesion assay and adhesion molecule expression. ROS production was detected by measuring the formation of lipid peroxidation malondialdehyde (MDA) through the thiobarbituric acid reactive substance (TBARS) assay. Peroxynitrite (ONOO⁻) formation was tested using the 3-nitrotyrosine ELISA kit. Iodixanol impaired cell viability, promoted vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1) expression, and induced cell apoptosis in human umbilical vein endothelial cells (HUVECs). However, D-4F mitigated these injuries. Furthermore, iodixanol induced the phosphorylation of protein kinase C (PKC) beta II, p47, Rac1, and endothelial nitric oxide synthase (eNOS) at Thr495, which elicited ROS release and ONOO⁻ generation. D-4F inhibited NADPH oxidase (NOX) activation, ROS production, and ONOO⁻ formation via the AMP-activated protein kinase (AMPK)/PKC pathway. Additionally, after an intravascular injection of iodixanol in Sprague Dawley rats, iodixanol induced a remarkable inflammatory response in arterial endothelial cells, although significant apoptosis and morphological changes were not observed. D-4F alleviated the vessel inflammation resulting from iodixanol in vivo. Collectively, besides scavenging ROS, D-4F could also suppress ROS production and ONOO⁻ formation through the AMPK/PKC pathway, which ameliorated oxidative injuries in endothelial cells. Hence, D-4F might serve as a potential agent in preventing CI-AKI.

Antibiotics are currently extensively used in human medicine, animal farming, agriculture and aquaculture, and their residue has become a global environmental problem. However, the effects of antibiotic on other pollutants in aquatic environment are still poorly understood. In this study, the influences of norfloxacin on the residue, degradation and distribution of the herbicides (simazine, atrazine, terbuthylazine, acetochlor and metolachlor) and the enantioselectivity of acetochlor in sediment and water-sediment microcosm system were investigated. Sediment was spiked with norfloxacin and water was contaminated by herbicides to simulate environmental pollution. The amounts of herbicides in water and sediment samples were analyzed within 30 days of cultivation. The results showed that norfloxacin could significantly inhibit the dissipation, lengthen the half-lives and enhance the residues of herbicides in sediment. Take simazine as an example, its half-life significantly increased from 16.1 days to 19.3 days and its residual percentage grew from 24.2% to 30.4% when sediment was contaminated with 5 mg·kg−1 norfloxacin. However, only acetochlor degradation was significantly inhibited by norfloxacin in water-sediment microcosm and the distribution of the herbicides were not affected. Enantioselective degradation of acetochlor was observed both in control and norfloxacin-treated water-sediment system, with R-acetochlor preferential elimination, suggesting the co-existence of norfloxacin had very limited influence on the enantioselectivity. The findings indicated that co-contamination with norfloxacin could increase the persistence of herbicides in aquatic environment, thus increasing the environmental risks to aquatic organisms.

Abstract Background Disruption of the gut microbiota homeostasis may induce low-grade inflammation leading to obesity-associated diseases. A major protective mechanism is to use the multi-layered mucus structures to keep a safe distance between gut epithelial cells and microbiota. To investigate whether pesticides would induce insulin resistance/obesity through interfering with mucus-bacterial interactions, we conducted a study to determine how long-term exposure to chlorpyrifos affected C57Bl/6 and CD-1 (ICR) mice fed high- or normal-fat diets. To further investigate the effects of chlorpyrifos-altered microbiota, antibiotic treatment and microbiota transplantation experiments were conducted. Results The results showed that chlorpyrifos caused broken integrity of the gut barrier, leading to increased lipopolysaccharide entry into the body and finally low-grade inflammation, while genetic background and diet pattern have limited influence on the chlorpyrifos-induced results. Moreover, the mice given chlorpyrifos-altered microbiota had gained more fat and lower insulin sensitivity. Conclusions Our results suggest that widespread use of pesticides may contribute to the worldwide epidemic of inflammation-related diseases.

Abstract Background Antibiotics are commonly used worldwide, and pesticide is a kind of xenobiotic to which humans are frequently exposed. The interactive impact of antibiotics on pesticides has rarely been studied. We aim to investigate the effects of antibiotics on the pesticide exposure risk and whether gut microbiota altered by antibiotics has an influence on pesticide bioavailability. Furthermore, we explored the mechanisms of gut microbiota affecting the fate of pesticides in the host. Results The oral bioavailability of triazine herbicides significantly increased in the rats treated with ampicillin or antibiotic cocktails. The antibiotic-altered gut microbiota directly influenced the increased pesticide bioavailability through downregulating hepatic metabolic enzyme gene expression and upregulating intestinal absorption-related proteins. Conclusions Antibiotics could increase the pesticide bioavailability and thereby may increase the pesticide exposure risk. The antibiotic-altered gut microbiota that could alter the hepatic metabolic enzyme gene expression and intestinal absorption-related proteome was a critical cause of the increased bioavailability. This study revealed an undiscovered potential health impact of antibiotics and reminded people to consider the co-exposed xenobiotics when taking antibiotics.

Infectious coryza is an acute infectious respiratory disease in chickens that is caused by Avibacterium paragallinarum (A. paragallinarum). Infectious coryza has major economic effects due to decreased egg production in growing birds and slowed growth in broilers. In this study, we isolated and identified 40 strains of A. paragallinarum from chickens that showed typical clinical signs of coryza in part of China from 2019 to 2020. Using a hemagglutination-inhibition test, 11 isolates were identified as serovar A, 10 isolates were identified as serovar B, and 19 isolates were identified as serovar C. Antimicrobial sensitivity tests showed that high minimum inhibitory concentration (MIC) values were encountered for compounds sulfamethoxine sodium and oxytetracycline hydrochloride. Especially, of the 40 A. paragallinarum isolates, 30% had an MIC value of compound sulfamethoxine sodium of 64 μg/mL, 10% of 128 μg/mL, and 15% of 256 μg/mL. For oxytetracycline hydrochloride, 85% of isolates showed MIC values of 64 μg/mL or more. Excitingly, the MIC values of β-lactamase (amoxicillin, ampicillin, and ceftiofur) were low, with 77.5%, 70%, and 92.5% of isolates having an MIC value of ≤1 μg/mL, respectively. Our results may provide a reference for the treatment of infectious coryza.

Localization capability is a challenging task in global navigation satellite system-degraded or denied environments. Alternatively, today’s smartphones have an increased number of integrated sensors that can act as terminals for indoor personal positioning solutions such as pedestrian dead reckoning (PDR). However, magnetic interference, poor sensor measurements, and diverse handling of smartphone quickly decrease the performance for indoor PDR. This paper proposes a comprehensive and novel pedestrian indoor positioning solution in which heading estimation is improved by using simplified magnetometer calibration, by calculating projected acceleration along the moving direction using frequency-domain features and by applying direction constrains to indoor accessible paths. Moreover, compared with an ordinary particle filter (OPF) and a Kalman filter, this paper proposes a multidimensional particle filter (MPF) algorithm, namely MPF, which includes high-dimensional variables such as position, heading, step length parameters, motion label, lifetime, number of current particles, and factor. An MPF can handle more uncertain parameters than the OPF. Therefore, positioning with an MPF can achieve lower errors using low-quality sensors, mitigate interference introduced from surrounding environments, and reduce heading ambiguities due to different modes of carrying a smartphone. Consequently, field tests show that the proposed algorithm obtains robust performance for heading estimation and positioning.

Intravenous injection is a standard procedure for delivering human stem cells and therapeutic agents. Currently, genetically modified severe combined immunodeficiency (SCID) mice are used for engraftment studies using human cells. SCID neonates have better integration and survivability of human cells compared to adult SCID mice, as their immune system will not be developed in the first few days after birth. However, intravenous injections in neonates are difficult. This protocol describes a reliable and reproducible method for injecting cells into the facial vein of P3/P4 (3 or 4 days post-birth) SCID neonates to study their engraftment. The injection was safe and well tolerated by the pups. Post-injection analysis revealed the distribution of tagged cells in different organs. Results suggest that this new method can serve as a pre-analysis for transplantation studies using human stem cells before in vivo animal model testing. Method name: Facial vein injection in P3/P4 pups, Keywords: Neonates, Facial vein, Intravenous injection, Stem cells, Delivery

Neurological disorders are big public health challenges that are afflicting hundreds of millions of people around the world. Although many conventional pharmacological therapies have been tested in patients, their therapeutic efficacies to alleviate their symptoms and slow down the course of the diseases are usually limited. Cell therapy has attracted the interest of many researchers in the last several decades and has brought new hope for treating neurological disorders. Moreover, numerous studies have shown promising results. However, none of the studies has led to a promising therapy for patients with neurological disorders, despite the ongoing and completed clinical trials. There are many factors that may affect the outcome of cell therapy for neurological disorders due to the complexity of the nervous system, especially cell types for transplantation and the specific disease for treatment. This paper provides a review of the various cell types from humans that may be clinically used for neurological disorders, based on their characteristics and current progress in related studies.

Background: The prevalence of obesity has raised global concerns. Environmental pollutants are one of the main causes of obesity. Many studies have demonstrated that dietary fiber could reduce obesity induced by high-fat diets, but whether environmental pollutant-induced obesity can be reversed is still unknown. Objectives: This study aimed to investigate the effects of pectin on obesity induced by a typical environmental pollutant p,p'-dichlorodiphenyldichloroethylene (p,p′-DDE) and explore the underlying mechanism by which pectin reversed p,p′-DDE-induced obesity. Methods: p,p′-DDE was used to induce obesity in C57BL/6J mice and pectin was supplied during and after cessation of p,p'-DDE exposure. Body and fat weight gain, plasma lipid profile and insulin resistance of mice were assessed. Gut microbiota composition and the levels of short-chain fatty acids (SCFAs) as well as the receptor proteins and hormones in the SCFAs-related signaling pathway were analyzed. Moreover, p,p′-DDE levels in various tissues of mice were detected. Results: Pectin supplementation reversed body and fat weight gain, dyslipidemia, hyperglycemia and insulin resistance in p,p′-DDE-exposed mice. Furthermore, pectin apparently altered the p,p′-DDE-induced microbial composition and then promoted the levels of SCFAs in colonic feces as well as the expression of G-protein coupled receptors and the concentration of hormone peptide YY (PYY) and glucagon like peptide-1 (GLP-1). Pectin treatment also significantly reduced p,p′-DDE accumulation in mice tissues during p,p′-DDE exposure but did not change p,p′-DDE metabolism after termination of p,p′-DDE exposure. Conclusions: Pectin had a good effect on reducing p,p′-DDE-induced obesity through regulating gut microbiota and provided a potential strategy for the treatment of environmental pollutant-caused health problems. Keywords: p,p′-DDE, Obesity, Pectin, Gut microbiota

Apolipoprotein A-I (apoA-I) mimetic peptide, D-4F, exhibits anti-atherogenic effects similar to high-density lipoprotein (HDL). However, it remains elusive whether D-4F and HDL share similar molecular mechanisms underlying anti-atherogenic effects and endothelial cell protections. We here compared the metabolic changes in endothelial cells induced by D-4F and HDL against oxidized low-density lipoprotein (ox-LDL), which may be of benefit to understanding the protective mechanisms of HDL and D-4F. Functional assays, including wound healing, transwell migration, and tube formation, were used to evaluate the pro-angiogenic effects of HDL and D-4F. NMR-based metabolomic analysis was employed to explore the protective mechanisms underlying HDL and D-4F. Partial least-squares discriminant analysis (PLS-DA) was performed to assess metabolic profiles, and orthogonal PLS-DA (OPLS-DA) was carried out to identify characteristic metabolites. Moreover, significantly altered metabolic pathways were also analyzed. We found that ox-LDL impaired the migration and tube formation of endothelial cells. Metabolomic analysis showed that ox-LDL triggered oxidative stress, impaired glycolysis, and enhanced glycerophospholipid metabolism. Both HDL and D-4F improved the migration and angiogenesis of endothelial cells, alleviated oxidative stress, and ameliorated disordered glycolysis impaired by ox-LDL. Strikingly, HDL partially attenuated the disturbed glycerophospholipid metabolism, whereas D-4F did not show this effect. In summary, although D-4F shared the similar protective effects with HDL on the migration and angiogenesis of endothelial cells, it could not deduce the molecular mechanisms of HDL completely. Nevertheless, D-4F possesses the potentiality to be exploited as clinically applicable agent for endothelial cell protection and cardiovascular disease treatment.

Endothelial dysfunction plays key roles in the pathological process of contrast media (CM)-induced acute kidney injury (CI-AKI) in patients undergoing vascular angiography or intervention treatment. Previously, we have demonstrated that an apolipoprotein A-I (apoA-I) mimetic peptide, D-4F, inhibits oxidative stress and improves endothelial dysfunction caused by CM through the AMPK/PKC pathway. However, it is unclear whether CM induce metabolic impairments in endothelial cells and whether D-4F ameliorates these metabolic impairments. In this work, we evaluated vitalities of human umbilical vein endothelial cells (HUVECs) treated with iodixanol and D-4F and performed nuclear magnetic resonance (NMR)-based metabolomic analysis to assess iodixanol-induced metabolic impairments in HUVECs, and to address the metabolic mechanisms underlying the protective effects of D-4F for ameliorating these metabolic impairments. Our results showed that iodixanol treatment distinctly impaired the vitality of HUVECs, and greatly disordered the metabolic pathways related to energy production and oxidative stress. Iodixanol activated glucose metabolism and the TCA cycle but inhibited choline metabolism and glutathione metabolism. Significantly, D-4F pretreatment could improve the iodixanol-impaired vitality of HUVECs and ameliorate the iodixanol-induced impairments in several metabolic pathways including glycolysis, TCA cycle and choline metabolism in HUVECs. Moreover, D-4F upregulated the glutathione level and hence enhanced antioxidative capacity and increased the levels of tyrosine and nicotinamide adenine dinucleotide in HUVECs. These results provided the mechanistic understanding of CM-induced endothelial impairments and the protective effects of D-4F for improving endothelial cell dysfunction. This work is beneficial to further exploring D-4F as a potential pharmacological agent for preventing CM-induced endothelial impairment and acute kidney injury.

Objective: We have previously shown that monomeric-C-reactive protein is deposited in significant quantities within the brain parenchyma after stroke. Since we have recently identified a possible role of this protein in supporting neurodegeneration and aberrant vascular development we identified a small group of post-mortem brain samples from individuals who had Alzheimer’s disease and evidence of tissue infarction/ micro-infarction on histological examination. Material and Method: We used immunohistochemistry staining to identify the monomeric-C-reactive protein expressed in the infarcted brain tissues. Results: We showed that monomeric-C-reactive protein deposition was highest in those regions affected by stroke or vascular disruption, and that within those same areas, there was more interaction and co-localization between major classical proteins of neurodegeneration (β-amyloid and tau). Conclusion: We hypothesise that vascular disruption and concomitant release of monomeric-C-reactive protein within the brain tissue could exacerbate ongoing neurological damage via stimulation of neuro-inflammation and from direct consequences of its action on both neuronal and vascular cells.

The thermal characteristics of Paulownia sawdust (PS), bamboo sawdust (BS), rice lemma (RL), and corncob (CC) in an oxidizing atmosphere were investigated using thermogravimetric analysis. The results indicated that the reaction of biomass oxidative decomposition took place in two main phases: devolatilization and char oxidation. Among various types of biomass, BS was found to possess the highest oxidative decomposition reactivity followed by PS, CC, and RL. Additionally, an increase in heating rate led to a significant improvement of the reactivity. The kinetic modeling of the oxidation reaction with the direct fitting method using the DRPM model showed a satisfied match with the experimental data, and the activation energy of biomass during the devolatilization process was higher than that of the char oxidation process. The activation energy of devolatilization was in the range of 80.7 to 133.8 kJ/mol, while that value of char oxidation fluctuated between 41.7 and 67.5 kJ/mol. In addition, with an increase in the heating rate, a marked compensation effect between the activation energy and pre-exponential factors was observed.

Objectives: In this study, we examined the possibility of using targeted antibodies and the potential of small molecular therapeutics (acetylcholine, nicotine and tacrine) to block the pro-inflammatory and adhesion-related properties of monomeric C-reactive protein (mCRP).Methods: We used three established models (platelet aggregation assay, endothelial leucocyte binding assay and monocyte inflammation via ELISA and Western blotting) to assess the potential of these therapeutics.Results: The results of this study showed that monocyte induced inflammation (raised tumor necrosis factor-alpha-TNF-α) induced by mCRP was significantly blocked in the presence of acetylcholine and nicotine, whilst tacrine and targeted antibodies (clones 8C10 and 3H12) had less of or no significant effects. Western blotting confirmed the ability of acetylcholine to inhibit mCRP-induced cell signaling phosphorylation of extracellular signal regulated kinase 1/2 (ERK1/2), p38 and nuclear factor-kappa B (NF-κB). There was no evidence of direct binding between small molecules and mCRP. mCRP also induced endothelial cell-monocyte adhesion in a dose dependent fashion, however, both acetylcholine and nicotine as well as targeting antibodies notably inhibited adhesion. Finally, we investigated their effects on mCRP-induced platelet aggregation. All three small molecules significantly attenuated platelet aggregation as did the antibody 8C10, although 3H12 had a weaker effect.Discussion: Acetylcholine and to a lesser extent nicotine show potential for therapeutic inhibition of mCRP-induced inflammation and cell and platelet adhesion. These results highlight the potential of targeted antibodies and small molecule therapeutics to inhibit the binding of mCRP by prevention of membrane interaction and subsequent activation of cellular cascade systems, which produce the pro-inflammatory effects associated with mCRP.

Circulating C-reactive protein (CRP) is a key acute-phase protein and one of the main clinical biomarkers for inflammation and infection. CRP is an important upstream mediator of inflammation and is associated with the onset of a number of important disease states including cardiovascular disease and neurodegenerative disorders such as Alzheimer’s disease. This pentraxin exerts pro-inflammatory properties via dissociation of the pentamer (pCRP) to a monomeric form (mCRP). This dissociation is induced by binding of pCRP to cell surface phosphocholine residues exposed by the action of phospholipase A2 (PLA2). Given the association of CRP with the onset of a range of serious disease states this CRP dissociation process is a tempting drug target for the development of novel small-molecule therapeutics. This review will discuss potential targets for chemotherapeutic intervention elucidated during studies of CRP-mediated inflammation and provide an up-to-date summary of the development of small molecules, not only targeted directly at inhibiting conversion of pCRP to mCRP, but also those developed for activity against PLA2, given the key role of this enzyme in the activation of CRP.

The tail-sitter Vertical Takeoff and Landing (VTOL) Unmanned Aerial Vehicle(UAV), flying in a fixed-wing model, overcomes many shortcomings of traditional fixed-wing UAVs, and inherits the advantage of high overall efficiency, which means it has great development potential and very broad application prospects. The attitude of tail-sitter VTOL UAV shows a wide change range in its takeoff and landing stages, and when the attitude sensor changes more than 90 degrees in pitch direction, the Euler angles converted by the Quaternions will have singular points, which means gimbal deadlock appears. From the solution algorithm, this paper provides a method of changing the order of rotation to avoid the appearance of singular points. The results show that this method can be well applied to the attitude solution of the VTOL UAV.