Suppression of MyD88-dependent signaling alleviates neuropathic pain induced by peripheral nerve injury in the rat

Abstract Background MyD88 is the adaptor protein of MyD88-dependent signaling pathway of TLRs and IL-1 receptor and regulates innate immune response. However, it was not clear whether and how MyD88 and related signaling pathways in the dorsal root ganglion (DRG) and spinal dorsal horn (SDH) are involved in neuropathic pain. Methods Chronic constriction injury (CCI) was used to induce neuropathic pain in the rat. The expression of MyD88, TRIF, IBA1, and GFAP was detected with immunofluorescent staining and Western blot. The expression of interleukin-1 beta (IL-1β), high mobility group box 1 (HMGB1), NF-κB-p65, phosphorylated NF-κB-p65, ERK, phosphorylated ERK, and tumor necrosis factor-alpha (TNF-α) was detected with Western blot. Pain-related behavioral effects of MyD88 homodimerization inhibitory peptide (MIP) were accessed up to 3 weeks after intrathecal administration. Results Peripheral nerve injury significantly increased the protein level of MyD88 in the DRG and SDH, but had no effect on TRIF. MyD88 was found partly distributed in the nociceptive neurons in the DRGs and the astrocytes and microglia in the SDH. HMGB1 and IL-1β were also found upregulated in nociceptive pathways of CCI rats. Intrathecal application of MIP significantly alleviated mechanical and thermal hyperalgesia in the CCI rats and also reversed CCI-induced upregulation of MyD88 in both DRG and SDH. Further investigation revealed that suppression of MyD88 protein reduced the release of TNF-α and glial activation in the SDH in the CCI rats. Conclusions MyD88-dependent TIR pathway in the DRG and SDH may play a role in CCI-induced neuropathic pain. MyD88 might serve as a potential therapeutic target for neuropathic pain

Fibrinogen-to-prealbumin ratio: A new prognostic marker of resectable pancreatic cancer

BackgroundThe fibrinogen-to-prealbumin ratio (FPR), a novel immune-nutritional biomarker, has been reported to be associated with prognosis in several types of cancer, but the role of FPR in the prognosis of resectable pancreatic cancer has not been elucidated.MethodsA total of 263 patients with resectable pancreatic cancer were enrolled in this study and were randomly divided into a training cohort (n = 146) and a validation cohort (n = 117). Receiver operating characteristic curve (ROC) was used to calculate the cut-off values of immune-nutritional markers. The least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression were performed in the training cohort to identify the independent risk factors, based on which the nomogram was established. The performance of the nomogram was evaluated and validation by the training and validation cohort, respectively.ResultsThe optimal cutoff value for FPR was 0.29. Multivariate analysis revealed that FPR, controlling nutritional status (CONUT), carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), and tumor node metastasis (TNM) stage were independent predictors of overall survival (OS). The nomogram was established by involving the five factors above. The C-index of the training cohort and validation cohort were 0.703 (95% CI: 0.0.646-0.761) and 0.728 (95% CI: 0.671-0.784). Decision curve analysis and time-dependent AUC showed that the nomogram had better predictive and discriminative ability than the conventional TNM stage.ConclusionFPR is a feasible biomarker for predicting prognosis in patients with resectable pancreatic cancer. The nomogram based on FPR is a useful tool for clinicians in making individualized treatment strategies and survival predictions

The complete reference genome for grapevine (Vitis vinifera L.) genetics and breeding

Grapevine is one of the most economically important crops worldwide. However, the previous versions of the grapevine reference genome consisted of thousands of fragments with missing centromeres and telomeres, which limited the accessibility of the repetitive sequences, the centromeric and telomeric regions, and the inheritance of important agronomic traits in these regions. Here, we assembled a telomere-to-telomere (T2T) gap-free reference genome for the pinot noir cultivar (PN40024) using the PacBio HiFi long reads. The T2T reference genome (PN_T2T) was 69 Mb longer with 9026 more genes identified than the 12X.v2 version (Canaguier et al., 2017). We annotated 67% repetitive sequences, 19 centromeres and 36 telomeres, and incorporated gene annotations of previous versions into the PN_T2T. We detected a total of 377 gene clusters, which showed associations with complex traits, such as aroma and disease resistance. Even though the PN40024 sample had been selfed for nine generations, we still found nine genomic hotspots of heterozygous sites associated with biological processes, such as the oxidation-reduction process and protein phosphorylation. The fully annotated complete reference genome, therefore, provides important resources for grapevine genetics and breeding.This work was supported by the National Natural Science Fund for Excellent Young Scientists Fund Program (Overseas) to Yongfeng Zhou, the National Key Research and Development Program of China(grant2019YFA0906200), the Agricultural Science and Technology Innovation Program (CAAS-ZDRW202101), the Shenzhen Science and Technology Program (grant KQTD2016113010482651), the BMBF funded de.NBI Cloud within the German Network for Bioinformatics Infrastructure (de.NBI). We thank Bianca Frommer, Marie Lahaye, David Navarro-Payá, Marcela K. Tello-Ruiz and Kapeel Chougule for their help in analyzing the RNA-Seq data and in running the gene annotation pipeline. This study is also based upon work from COST Action CA17111 INTEGRAPE and form COST Innovators Grant IG17111 GRAPEDIA, supported by COST (European Cooperation in Science and Technology).ViticultureT2Tgap-fregene clustercentromeretelomerePublishe

Development of Metal Polishing Dust Monitoring System using the Internet of Things and Cloud Server

In order to increase the management efficiency and decrease the maintenance costs in the traditional dust monitoring system, a novel real-time remote monitoring system using the Internet of Things and cloud server is proposed in this paper. The system includes several sensor nodes, a sink node and Cloud Server. The high-precision dust probe, temperature and humidity sensors, water flow sensors and hydrogen transmitters are integrated together into a sensor node to access the metal polished environmental information. Then, the collected information is transmitted to sink-node using the 2.4G wireless network. The sink-node uploads data to the Cloud Server through the 4G network and TCP Socket. Based on the Browser/Server (B/S) model, a remote monitoring system is developed by using Tencent Cloud Server, C# language, and SQL database. As a result, the on-site metal polishing environmental information is obtained via the App and Web page

Development of Metal Polishing Dust Monitoring System using the Internet of Things and Cloud Server

In order to increase the management efficiency and decrease the maintenance costs in the traditional dust monitoring system, a novel real-time remote monitoring system using the Internet of Things and cloud server is proposed in this paper. The system includes several sensor nodes, a sink node and Cloud Server. The high-precision dust probe, temperature and humidity sensors, water flow sensors and hydrogen transmitters are integrated together into a sensor node to access the metal polished environmental information. Then, the collected information is transmitted to sink-node using the 2.4G wireless network. The sink-node uploads data to the Cloud Server through the 4G network and TCP Socket. Based on the Browser/Server (B/S) model, a remote monitoring system is developed by using Tencent Cloud Server, C# language, and SQL database. As a result, the on-site metal polishing environmental information is obtained via the App and Web page

A comprehensive model considering multiple types of occupant behavior for building energy performance prediction and simulation - taking a university campus as an example

Occupant behavior, encompassing occupant numbers and actions, significantly contributes to the uncertainty of building energy performance simulation. By characterizing the regularity of occupant behavior, it becomes feasible to evaluate its impact on building energy consumption and mitigate disparities between simulated and measured outcomes. This paper presents a comprehensive model that integrates two key aspects of occupant behavior to predict and simulate energy performance in campus buildings. The model introduces two distinct categories of equipment, namely environment-related equipment (e.g. lighting, air conditioning) and time-related equipment (e.g. water dispenser, printer), to account for the diverse factors that influence occupant behavior. The impact of occupant perception on the environment is considered to enhance simulation accuracy. Furthermore, this study compares the proposed model with models that consider only occupant number or occupant energy use behavior individually to assess its effectiveness in capturing the complexities of occupant behavior in energy performance simulations

Optimizing Tillage and Fertilization Patterns to Improve Soil Physical Properties, NUE and Economic Benefits of Wheat-Maize Crop Rotation Systems

Winter wheat and summer maize rotation is the main cropping pattern in the North China Plain (NCP). There are still problems with farmers’ production modes, including shallow tillage layers, single application of chemical fertilizer causing plow bottom layer thickening and soil pH decrease. A two-factor location experiment was conducted to investigate the effects of different tillage and fertilization patterns on the soil physical properties, soil organic carbon (SOC), nitrogen-use efficiency, and crop yield of wheat–maize rotation systems during the years 2018–2020. The different treatments were deep tillage + organic fertilizer (DTF), shallow tillage + organic fertilizer (STF), no tillage + organic fertilizer (NTF), deep tillage + nitrogen fertilizer (DT), shallow tillage + nitrogen fertilizer (ST), and no tillage + nitrogen fertilizer (NT). The results showed that STF treatment could effectively improve the physical properties of soil and, SOC content, and increase both the crop yield and revenue of farmers. In the STF treatment, soil water content was highest in the 0–20 cm layer (2018), which was 4.89–11.31% higher than that of the other treatments; additional organic fertilizer application reduced soil bulk and increased the proportion of <0.25 mm aggregates; SOC and soil total nitrogen (TN) content were highest in the 20–40 cm layer, (15.82–32.63% and 28.57–42.86%, respectively). The total yield of wheat–maize rotation for both years was the highest under STF treatment. The annual economic benefits under this treatment were 42,182.26 and 42,254.54 CNY ha−1, which were 1.02–12.94% and 2.29–9.87% higher than those of the other treatments. Therefore, the suggested planting method in the NCP is tillage of over 20 cm and additional organic fertilizer

Anlotinib Suppressed Ovarian Cancer Progression via Inducing G2/M Phase Arrest and Apoptosis

Ovarian cancer remains the most common gynecologic malignancy, because of its chemotherapy resistance and relapse. Anlotinib, a new oral multi-targeted tyrosine kinase inhibitor, has shown encouraging antitumor activity in several preclinical and clinical trials, while its effect on ovarian cancer has not been reported. In this study, we investigated the antitumor activity and underlying mechanism of anlotinib in ovarian cancer. Cell viability was analyzed by Cell Counting Kit-8 assay. Migration was measured by wound-healing assay. The cell cycle distribution and cell apoptosis rate were detected by flow cytometry. In vivo antitumor effect was analyzed in mouse ovarian carcinoma peritoneal metastasis model. We found that anlotinib inhibited the proliferation of ovarian cancer cells in a dose- and time- dependent manner by inducing G2/M phase arrest and apoptosis. Moreover, anlotinib upregulated the the phosphorylation of Histone H3, and expression of p21 protein in vitro. In addition, anlotinib inhibited the migration of ovarian cancer cells in vitro. Furthermore, anlotinib inhibited tumor growth by inhibiting cell proliferation and suppressing ovarian cancer angiogenesis in vivo. This study demonstrated the extraordinary anti-ovarian cancer effect of anlotinib, which may provide a promising therapeutic strategy for ovarian cancer

Chronic constriction injury-induced microRNA-146a-5p alleviates neuropathic pain through suppression of IRAK1/TRAF6 signaling pathway

Abstract Background microRNA-146a-5p (miRNA-146a-5p) is a key molecule in the negative regulation pathway of TLRs and IL-1 receptor (TIR) signaling. Our recent study demonstrated that MyD88-dependent signaling pathway of TIR in the dorsal root ganglion (DRG) and spinal dorsal horn (SDH) plays a role in peripheral nerve injury-induced neuropathic pain. However, it was not clear whether and how miRNA-146a-5p regulates the TIR pathway of DRG and SDH in the development of neuropathic pain. Methods The sciatic nerve chronic constriction injury (CCI) model of rat was used to induce chronic neuropathic pain. The levels and cellular distribution of miRNA-146a-5p were detected with quantitative real-time PCR (qPCR) and fluorescent in situ hybridization (FISH). The RNA level, protein level, and cellular distribution of IRAK1 and TRAF6 that is targeted by miRNA-146a-5p were detected with qPCR, western blot, and immunofluorescent. The pain-related behavioral effect of miRNA-146a-5p was accessed after intrathecal administration. Mechanical stimuli and radiant heat were used to evaluate mechanical allodynia and thermal hyperalgesia. Results We found that the level of miRNA-146a-5p significantly increased in L4-L6 DRGs and SDH after CCI surgery; meanwhile, the protein level of IRAK1 and TRAF6 in DRGs was significantly increased after CCI. Intrathecal injection of miR146a-5p agomir or miRNA-146a-5p antagomir regulates miRNA-146a-5p level of L4-L6 DRGs and SDH. We found that intrathecal injection of miR146a-5p agomir can alleviate mechanical and thermal hyperalgesia in CCI rats and reverse the upregulation of IRAK1 and TRAF6 of L4-L6 DRGs and SDH induced by CCI. We furthermore found that intrathecal injection of miRNA-146a-5p antagomir can exacerbate the mechanical and thermal pain-related behavior of CCI rats and meanwhile increase IRAK1 and TRAF6 of L4-L6 DRGs and SDH expression even further. Conclusions miRNA-146a-5p of DRG and SDH can modulate the development of CCI-induced neuropathic pain through inhibition of IRAK1 and TRAF6 in the TIR signaling pathway. Hence, miRNA-146a-5p may serve as a potential therapeutic target for neuropathic pain

Silicon application mitigated the adverse effects of salt stress and deficit irrigation on drip-irrigated greenhouse tomato

Tomato (Solanum lycopersicum L.) is an important vegetable crop around the world, and water scarcity and soil salinization are two major unfavorable factors limiting the fruit yield and quality of greenhouse tomato in arid and semi-arid regions. The application of exogenous silicon has been reported to enhance tomato yield under salt or drought stress, but its effect under combined salt-drought stress remains unclear. A two-season (autumn 2021 and spring 2022) experiment was conducted with three irrigation levels (I1, 90%−100% θf, where θf is the field capacity; I2, 70%−80% θf; I3, 50%−60% θf), two soil salinity levels (S0, 0.1%, g/g; S1, 0.4%, g/g) and two silicon application rates (T0, 0 mM; T1, 2.4 mM) to explore their combined effects on leaf silicon content, photosynthetic parameters, fruit yield, nutrient yield, crop water productivity (WP), nitrogen uptake and utilization, nutrient water productivity (NWP) and economic benefit of drip-irrigated greenhouse tomato. The results showed that deficit irrigation and salt stress exerted significant inhibiting effects on leaf silicon content, photosynthetic parameters, tomato yield, and water-nitrogen productivity, but the inhibition was alleviated by silicon application, which increased leaf silicon content by 67.0%, net photosynthetic rate (Pn) by 25.3%, fruit yield by 12.3%, WP by 11.9%, nutrient yield by 10.0% (titratable acids) - 27.4% (soluble sugars) and NWP by 9.2% (titratable acids) - 26.1% (soluble sugars) on average. The average fruit yield over the two growing seasons was 66.01, 54.29 and 44.31 t ha−1 under I1, I2 and I3, and the silicon application increased average leaf silicon content by 71.9%, 65.2% and 63.0%, Pn by 11.1%, 12.9% and 7.6%, and fruit yield by 12.8%, 16.2%, and 8.1% at the three irrigation levels, respectively. Plant nitrogen uptake (NU) and nitrogen partial factor productivity (NPFP) increased but nitrogen use efficiency (NUE) tended to decrease with the increasing irrigation level, while silicon application improved NUE by 3.9% and 2.2% and NPFP by 13.8% and 11.7% in the two growing seasons, respectively. Silicon application significantly increased net profit by 24.3% and 17.7% in autumn 2021 and spring 2022, respectively. According to the principal component analysis, I1T1S0 ranked first in both growing seasons. The correlation matrix showed that fruit yield was positively correlated with leaf silicon content, Pn, stomatal conductance, WP, NU, NUE, NPFP, nutrient yield and net profit, while it had negative correlation with NWP. In conclusion, exogenous silicon application can improve the fruit yield and nutrient yield of drip-irrigated greenhouse tomato by enhancing leaf silicon content and photosynthetic capability under drought-stressed and salt-affected conditions