Plexin-B2 Mediates Physiologic and Pathologic Functions of Angiogenin.

Angiogenin (ANG) is a secreted ribonuclease (RNase) with cell-type- and context-specific roles in growth, survival, and regeneration. Although these functions require receptor-mediated endocytosis and appropriate subcellular localization, the identity of the cell surface receptor remains undefined. Here, we show that plexin-B2 (PLXNB2) is the functional receptor for ANG in endothelial, cancer, neuronal, and normal hematopoietic and leukemic stem and progenitor cells. Mechanistically, PLXNB2 mediates intracellular RNA processing that contribute to cell growth, survival, and regenerative capabilities of ANG. Antibodies generated against the ANG-binding site on PLXNB2 restricts ANG activity in vitro and in vivo, resulting in inhibition of established xenograft tumors, ANG-induced neurogenesis and neuroprotection, levels of pro-self-renewal transcripts in hematopoietic and patient-derived leukemic stem and progenitor cells, and reduced progression of leukemia in vivo. PLXNB2 is therefore required for the physiological and pathological functions of ANG and has significant therapeutic potential in solid and hematopoietic cancers and neurodegenerative diseases.

Would the one-stage combined approach lead to better long-term neurological outcomes than the posterior approach alone in multilevel degenerative cervical myelopathy patients with T2-Weighted increased signal intensity? An 8-year follow-up results and propensity score matching analysis.

BACKGROUND: T2-weighted increased signal intensity (ISI) is commonly recognized as a sign of more severe spinal cord lesions, usually accompanied by worse neurological deficits and possibly worse postoperative neurological recovery. The combined approach could achieve better decompression and better neurological recovery for multilevel degenerative cervical myelopathy (MDCM). The choice of surgical approach for MDCM with intramedullary T2-weighted ISI remains disputed. This study aimed to compare the neurological outcomes of posterior and one-stage combined posteroanterior approaches for MDCM with T2-weighted ISI. METHODS: A total of 83 consecutive MDCM patients with confirmed ISI with at least three intervertebral segments operated between 2012 and 2014 were retrospectively enrolled. Preoperative demographic, radiological and clinical condition variables were collected, and neurological conditions were evaluated by the Japanese Orthopedic Assessment score (JOA) and Neck Disability Index (NDI). Propensity score matching analysis was conducted to produce pairs of patients with comparable preoperative conditions from the posterior-alone and combined groups. Both short-term and mid-term surgical outcomes were evaluated, including the JOA recovery rate (JOARR), NDI improvements, complications, and reoperations. RESULTS: A total of 83 patients were enrolled, of which 38 and 45 patients underwent posterior surgery alone and one-stage posteroanterior surgery, respectively. After propensity score matching, 38 pairs of comparable patients from the posterior and combined groups were matched. The matched groups presented similar preoperative clinical and radiological features and the mean follow-up duration were 111.6 ± 8.9 months. The preoperative JOA scores of the posterior and combined groups were 11.5 ± 2.2 and 11.1 ± 2.3, respectively (p = 0.613). The combined group presented with prolonged surgery duration(108.8 ± 28.0 and 186.1 ± 47.3 min, p = 0.028) and greater blood loss(276.3 ± 139.1 and 382.1 ± 283.1 ml, p<0.001). At short-term follow-up, the combined group presented a higher JOARR than the posterior group (posterior group: 50.7%±46.6%, combined group: 70.4%±20.3%, p = 0.024), while no significant difference in JOARR was observed between the groups at long-term follow-up (posterior group: 49.2%±48.5%, combined group: 59.6%±47.6%, p = 0.136). No significant difference was found in the overall complication and reoperation rates. CONCLUSIONS: For MDCM patients with ISI, both posterior and one-stage posteroanterior approaches could achieve considerable neurological alleviations in short-term and long-term follow-up. With greater surgical trauma, the combined group presented better short-term JOARR but did not show higher efficacy in long-term neurological function preservation in patients with comparable preoperative conditions.

The miR-302/367 cluster: Aging, inflammation, and cancer.

MicroRNAs (miRNAs) are a class of noncoding RNAs that occupy a significant role in biological processes as important regulators of intracellular homeostasis. First, we will discuss the biological genesis and functions of the miR-302/367 cluster, including miR-302a, miR-302b, miR-302c, miR-302d, and miR-367, as well as their roles in physiologically healthy tissues. The second section of this study reviews the progress of the miR-302/367 cluster in the treatment of cancer, inflammation, and diseases associated with aging. This cluster's aberrant expression in cells and/or tissues exhibits similar or different effects in various diseases through molecular mechanisms such as proliferation, apoptosis, cycling, drug resistance, and invasion. This article also discusses the upstream and downstream regulatory networks of miR-302/367 clusters and their related mechanisms. Particularly because studies on the upstream regulatory molecules of miR-302/367 clusters, which include age-related macular degeneration, myocardial infarction, and cancer, have become more prevalent in recent years. MiR-302/367 cluster can be an important therapeutic target and the use of miRNAs in combination with other molecular markers may improve diagnostic or therapeutic capabilities, providing unique insights and a more dynamic view of various diseases. It is noted that miRNAs can be an important bio-diagnostic target and offer a promising method for illness diagnosis, prevention, and treatment.

Predicting post-laminoplasty kyphosis in cervical spondylotic myelopathy patients without preoperative kyphosis: a retrospective study.

BACKGROUND: This study aimed to determine potential risk factors for post-laminoplasty kyphosis and the effect of postoperative kyphosis on neurologic function recovery. METHODS: A total of 266 patients with cervical spondylotic myelopathy (CSM) underwent traditional cervical laminoplasty with a minimum of a 12-month follow-up period. The patients were divided into non-kyphosis (NK group) and kyphosis (K group) groups based on the postoperative C2-7 Cobb angle. Clinical and radiological measurements were collected preoperatively and at the final follow-up. RESULTS: Of the 266 patients, 26 (9.77%) developed postoperative kyphosis at the final follow-up. The postoperative Japanese Orthopedic Association score did not differ significantly between the NK and K groups (P > 0.05). The postoperative numeric rating scale (NRS) also showed no significant difference between the NK and K groups; however, postoperative NRS improved better than the preoperative values in the NK group (P < 0.001). Multivariate analysis revealed that the preoperative C2-7 extension Cobb angle and C2-7 Cobb angle were independent predictors of post-laminoplasty kyphosis. Cut-off values for predicting postoperative kyphosis were a C2-7 extension Cobb angle of 18.00° and a C2-7 Cobb angle of 9.30°. CONCLUSIONS: Low preoperative C2-7 extension Cobb angle and C2-7 Cobb angle may be associated with post-laminoplasty kyphosis in CSM patients without preoperative kyphosis. The cut-off value of the C2-7 extension Cobb angle and C2-7 Cobb angle were 18.00° and 9.30°, respectively.

TFAP2A inhibits microRNA-126 expression at the transcriptional level and aggravates ischemic neuronal injury.

Neuronal injury induced by cerebral ischemia poses a serious health risk globally, and there is no effective clinical therapy. This study was performed to investigate the role of transcription factor AP-2 alpha (TFAP2A) in cerebral ischemia, and the underlying mechanisms, using an in-vitro model (PC-12 cells) of oxygen-glucose deprivation (OGD), and an in-vivo model (rat) of transient global cerebral ischemia (tGCI). The results for CCK-8 and Hoechst staining showed that silencing of TFAP2A enhanced the viability and decreased the rate of apoptosis of PC12 cells subjected to OGD. ChIP assays were performed to evaluate the binding of TFAP2A to the promoter region of microRNA (miR)-126, and we found that TFAP2A inhibits the expression of miR-126. Further mechanistic investigation revealed that miR-126 targets polo like kinase 2 (PLK2), and that overexpression of PLK2 activates the IκBα-NF-κB signaling pathway and suppresses the growth of PC12 cells subjected to OGD. For our in-vivo assay, we used TTC staining to analyze the infarction area in the brain tissues of rats, and Nissl staining to evaluate the number of surviving brain neurons. The pathological conditions associated with neuronal injury in rat brain tissues were assessed by staining the tissues with hematoxylin-eosin. Our results indicate that TFAP2A downregulates miR-126, and thereby upregulates PLK2 and activates the IκBα-NF-κB pathway, which increased neuronal injury following cerebral ischemia.

Correlations of C-Reactive Protein (CRP), Interleukin-6 (IL-6), and Insulin Resistance with Cerebral Infarction in Hypertensive Patients.

BACKGROUND The aim of this study was to investigate the correlations of C-reactive protein (CRP), interleukin-6 (IL-6), and insulin resistance (IR) with cerebral infarction in hypertensive patients. MATERIAL AND METHODS A total of 80 patients with cerebral infarction admitted to our hospital from March 2016 to November 2017 were selected and divided into 2 groups according to the diameter of cerebral infarction, namely, lacunar cerebral infarction group (n=40) and cerebral infarction group (n=40). The levels of high-sensitivity CRP (hs-CRP) and IL-6, homeostasis model assessment of IR (HOMA-IR) index and blood pressure level were compared between the 2 groups. The correlations of hs-CRP level, IL-6 level, and IR with the diameter of cerebral infarction, as well as the relationships of hs-CRP level and IR with the neurological function score after cerebral infarction were analyzed. RESULTS The levels of hs-CRP and IL-6 in the cerebral infarction group were significantly higher than those in the lacunar cerebral infarction group (P<0.05). The cerebral infarction group had a markedly higher HOMA-IR index than the lacunar cerebral infarction group (P<0.05), but it had remarkably decreased systolic blood pressure and diastolic blood pressure compared with those in the lacunar cerebral infarction group (P<0.05). There were positive correlations of hs-CRP level, IL-6 level, and IR with the diameter of cerebral infarction (P<0.05). The hs-CRP level and IR had positive correlations with the neurological function score after cerebral infarction (P<0.05). CONCLUSIONS In hypertensive patients complicated with cerebral infarction, the body's inflammatory factors, and IR are positively correlated with the diameter of cerebral infarction, as well as the neurological prognosis of the patients.

Salvianolic Acid C Attenuates LPS-Induced Inflammation and Apoptosis in Human Periodontal Ligament Stem Cells via Toll-Like Receptors 4 (TLR4)/Nuclear Factor kappa B (NF-κB) Pathway.

BACKGROUND Periodontitis is a chronic inflammatory disease that causes gingival detachment and disintegration of alveolar bone. Salvianolic acid C (SAC) is a polyphenol compound with anti-inflammatory and antioxidant activities that is isolated from Danshen, a traditional Chinese medicine made from the roots of Salvia miltiorrhiza Bunge. The aim of this study was to investigate the mechanisms of underlying its protective effects and its inhibition effect on inflammation and apoptosis in human periodontal ligament stem cells (hPDLSCs). MATERIAL AND METHODS LPS-induced hPDLSCs, as a model mimicking an inflammatory process of periodontitis in vivo, were established to investigate the therapeutic effect of SAC in periodontitis. The inflammatory cytokines secretion and oxidative stress status were measured by use of specific commercial test kits. The hPDLSCs viability was analyzed by Cell Counting Kit-8 assay. The cell apoptosis and cell cycle were assayed with flow cytometry. Expressions levels of proteins involved in apoptosis, osteogenic differentiation, and TLR4/NF-kappaB pathway were evaluated by Western blotting. Alkaline phosphatase (ALP) activity was detected by ALP assay kit and ALP staining. The mineralized nodules formation of hPDLSCs was checked by Alizarin Red S staining. RESULTS Our results showed that LPS induced increased levels of inflammatory cytokines and oxidative stress and mediated the phosphorylation and nuclear translocation of NF­kappaB p65 in hPDLSCs. SAC reversed the abnormal secretion of inflammatory cytokines and inhibited the TLR4/NF­kappaB activation induced by LPS. SAC also upregulated cell viability, ALP activity, and the ability of osteogenic differentiation. The anti-inflammation and TLR4/NF­kappaB inhibition effects of SAC were reversed by TLR4 overexpression. CONCLUSIONS Taken together, our results revealed that SAC effectively attenuates LPS-induced inflammation and apoptosis via the TLR4/NF-kappaB pathway and that SAC is effective in treating periodontitis.

Sub-chronic 90-day toxicity of neamine in SD rats and its anti-liver cancer activity in vitro and in vivo.

Neamine, an inhibitor of angiogenin (ANG), is a new investigative anticancer drug currently in preclinical stage. Here we report the 90-day sub-chronic toxicity of neamine in SD rats and its anti-liver cancer activity in vitro and in vivo. Neamine has a No Observed Adverse Effect Level (NOAEL) of 12 and 16mg·kg-1·d-1 for female and male rats, respectively. No mortality was found. The adverse effects included increased organ coefficients of spleen and kidney, increased BUN in both female and male rats at high dose, increased CR and decreased organ coefficients of heart and liver in male rats at high dose. All of which, except the kidney coefficient and BUN in males, returned to normal levels after 28-day recovery. Histopathological examination revealed vacuolar degeneration of glomerulus, degeneration of renal tubules and cast in the kidneys, which were also recovered except in males of high-dosing group. These results indicate that kidney is the most susceptible organ for neamine toxicity. Tissue microarray analysis validated that ANG is up-regulated in hepatocellular carcinoma accompanied by increased nuclear translocation, suggesting that ANG is a possible target for drug development in liver cancer treatment. Neamine blocked nuclear translocation of ANG in HUVEC and HepG2 cells, and inhibited ANG-stimulated cell proliferation without affecting basal level cell proliferation. Neamine also inhibited progression of HepG2 xenografts in athymic mice accompanied by decreased angiogenesis and cancer cell proliferation. These results suggest that neamine is a specific ANG inhibitor with low toxicity and high anti-liver cancer efficacy.

[Analysis of medical cost of atlantoaxial disorders in patients receiving innovated treatment technologies].

OBJECTIVE: To explore the effects of innovated technologies and products on improving outcomes and decreasing medical costs by analyzing a total and subtotal medical costs of patients with atlantoaxial disorders. METHODS: The medical costs of 1 489 patients with atlantoaxial disorders from Peking University Third Hospital from 2005 to 2014, who received innovated technologies and products treatment were retrospectively analyzed and compared.Descriptive analysis and ANOVA were used for statistical analysis, and SPSS 19.0 was used to analyze data. RESULTS: From 2005 to 2014, under the situation of a general increase in medical cost by 327%, the total medical costs were stable for patients who used innovated technologies and products for treatment, fluctuating from 20 851 in 2005 to 20 878 in 2014; however, the cases of operation increased year by year, from 88 in 2005 to 163 in 2014; the average length of stay decreased from 21 in 2005 to 10 in 2014; the total cases of transfusion were 22 from 2005 to 2014; the safety, stability and feasibility of the innovated technologies and products were illustrated through the decrease of average length of stay, the reduction of bleeding and the significance of outcomes. CONCLUSION: It is illustrated that the innovated technologies and products not only decrease patients' suffering and medical costs but also are safe, stable and feasible.

Ultrasensitive Detection of MicroRNA in Tumor Cells and Tissues via Continuous Assembly of DNA Probe.

Nucleic acids have been engineered to participate in a wide variety of tasks. Among them, the enzyme-free amplification modes, enzyme-free DNA circuits (EFDCs), and hybridization chain reactions (HCRs) have been widely applied in a series of studies of bioanalysis. We demonstrated here an ultrasensitive hairpin probe-based circulation for continuous assemble of DNA probe. This strategy improved the analyte stability-dependent amplification efficiency of EFDC and signal enhancement without being limited by the analyte's initial concentration, and it was used to produce a novel microRNA (miRNA) trace analysis assay with ultrasensitive amplification properties. Through the detection of standard miRNA substances, 1 amol-level sensitivity and satisfactory specificity were achieved. Compared with EFDCs and HCRs, the sensitivity of ultrasensitive hairpin probe-based circulation was higher by 3 or 4 orders of magnitude. Furthermore, the excellent performance of this platform was also demonstrated in the detection of miRNAs in tumor cells. The sensitivities for the detection of miRNAs in HepG2, A549 and MCF-7 tumor cells were 10, 10, and 100 cells, respectively. In addition, a high detection rate of 83% was achieved for tumor tissues. Thus, this ultrasensitive hairpin probe-based circulation possesses the potential to be a technological innovation in the field of tumor diagnosis.

Target-triggered enzyme-free amplification strategy for sensitive detection of microRNA in tumor cells and tissues.

MicroRNAs (miRNAs) participate in important processes of life course. Because of their characters of small sizes, vulnerable degradabilities, and sequences similarities, the existing detection technologies mostly contain enzymatic amplification reactions for acquisition of high sensitivities and specificities. However, specific reaction conditions and time-dependent enzyme activities are caused by the accession of enzymes. Herein, we designed a target-triggered enzyme-free amplification platform that is realized by circulatory interactions of two hairpin probes and the integrated electrochemiluminescence (ECL) signal giving-out component. Benefiting from outstanding performances of the enzyme-free amplification system and ECL, this strategy is provided with a simplified reaction process, high sensitivity, and operation under isothermal conditions. Through detection of the miRNA standard substance, the sensitivity of this platform reached 10 fmol, and a splendid specificity was achieved. We also analyzed three tumor cell lines (human lung adenocarcinoma, breast adenocarcinoma, and hepatocellular liver carcinoma cell lines) through this platform. The sensitivities of 10(3) cells, 10(4) cells, and 10(4) cells were, respectively, achieved. Furthermore, clinical tumor samples were tested, and 21 of 30 experimental samples gave out positive signals. Thus, this platform possesses potentials to be an innovation in miRNA detection methodology.

Aggregation-Induced Emission-Based Macrophage-Like Nanoparticles for Targeted Photothermal Therapy and Virus Transmission Blockage in Monkeypox.

The recent prevalence of monkeypox has led to the declaration of a Public Health Emergency of International Concern. Monkeypox lesions are typically ulcers or pustules (containing high titers of replication-competent virus) in the skin and mucous membranes, which allow monkeypox virus to transmit predominantly through intimate contact. Currently, effective clinical treatments for monkeypox are lacking, and strategies for blocking virus transmission are fraught with drawbacks. Herein, this work constructs a biomimetic nanotemplate (termed TBD@M NPs) with macrophage membranes as the coat and polymeric nanoparticles loading a versatile aggregation-induced emission featured photothermal molecule TPE-BT-DPTQ as the core. In a surrogate mouse model of monkeypox (vaccinia-virus-infected tail scarification model), intravenously injected TBD@M NPs show precise tracking and near-infrared region II fluorescence imaging of the lesions. Upon 808 nm laser irradiation, the virus is eliminated by the photothermal effect and the infected wound heals rapidly. More importantly, the inoculation of treated lesion tissue suspensions does not trigger tail infection or inflammatory activation in healthy mice, indicating successful blockage of virus transmission. This study demonstrates for the first time monkeypox theranostics using nanomedicine, and may bring a new insight into the development of a viable strategy for monkeypox management in clinical trials.

Photothermal therapy of tuberculosis using targeting pre-activated macrophage membrane-coated nanoparticles.

Conventional antibiotics used for treating tuberculosis (TB) suffer from drug resistance and multiple complications. Here we propose a lesion-pathogen dual-targeting strategy for the management of TB by coating Mycobacterium-stimulated macrophage membranes onto polymeric cores encapsulated with an aggregation-induced emission photothermal agent that is excitable with a 1,064 nm laser. The coated nanoparticles carry specific receptors for Mycobacterium tuberculosis, which enables them to target tuberculous granulomas and internal M. tuberculosis simultaneously. In a mouse model of TB, intravenously injected nanoparticles image individual granulomas in situ in the lungs via signal emission in the near-infrared region IIb, with an imaging resolution much higher than that of clinical computed tomography. With 1,064 nm laser irradiation from outside the thoracic cavity, the photothermal effect generated by these nanoparticles eradicates the targeted M. tuberculosis and alleviates pathological damage and excessive inflammation in the lungs, resulting in a better therapeutic efficacy compared with a combination of first-line antibiotics. This precise photothermal modality that uses dual-targeted imaging in the near-infrared region IIb demonstrates a theranostic strategy for TB management.

Ovarian stimulation leads to a severe implantation defect in mice.

The aim of the present study was to evaluate whether ovarian stimulation could induce embryo implantation dysfunction in mice and to explore the possible mechanisms involved. Ovarian stimulation was performed with intraperitoneal injections of 0, 2.5, 5.0, 7.5 and 10.0 IU pregnant mare serum gonadotrophin followed by the same dose of human chorionic gonadotrophin 48h later. A dose-dependent implantation defect in stimulated mice was demonstrated, which can be mainly explained by premature luteolysis and secondary endometrial changes induced by an imbalance in oestradiol and progesterone.

DS147 improves pregnancy in mice with embryo implantation dysfunction induced by controlled ovarian stimulation.

The study examined the effect of DS147, the bioactive component of the traditional herbal recipe Bangdeyun, on pregnancy in mice with embryo implantation dysfunction induced by controlled ovarian stimulation (COS), and the underlying mechanisms. Female mice were superovulated by intraperitoneal injection of 7.5 IU of pregnant mare serum gonadotropin (PMSG) followed by an additional injection of 7.5 IU hCG 48 h later to establish embryo implantation dysfunction (EID) model. Pregnant mice were randomly divided into normal control group, COS group and DS147-treated groups. The pregnancy rate and the average implantation site were obtained on pregnancy day 8 (PD8). The side effect of 200 mg/kg of DS147 on naturally pregnant mice was also observed. Further, the uterine and ovarian tissue samples were collected on PD5 for measuring their weights, observing the development of the endometrium and ovary, and detecting the endometrial expression of MMP-2, TIMP-2, CD34 and angiogenin (ANG). The female mice treated with DS147 at doses of 100 to 800 mg/kg showed a higher pregnancy rate than those in COS group, and the highest pregnancy rate of 83.3% occurred in the 200 mg/kg DS147-treated group. Moreover, no obvious side effect was found in mice treated with 200 mg/kg DS147 on PD8 and PD16. The ovarian and uterine weights, and the expression levels of MMP-2, ANG and CD34 were significantly increased in DS147-treated groups when compared with COS group. The TIMP-2 expression level was much lower in DS147-treated mice than in COS mice and the ratio of MMP-2/TIMP-2 was much higher in DS147-treated group than in COS group, and even higher than normal control group. In all, these findings suggest that DS147 may improve pregnancy in mice with COS-induced EID by promoting matrix degradation and angiogenesis, and improving the development of corpus luteum and endometrial decidualization around the implantation window.

Investigation of the Degradation Mechanism of SiC MOSFET Subjected to Multiple Stresses.

The performance requirements for power devices in airborne equipment are increasingly demanding, while environmental and working stresses are becoming more diverse. The degradation mechanisms of devices subjected to multiple stresses become more complex. Most proposed degradation mechanisms and models in current research only consider a single stress, making it difficult to describe the correlation between multiple stresses and the correlation of failures. Then, a multi-physical field coupling model based on COMSOL is proposed. The influence relationship between temperature, moisture, electrical load, and vibration during device operation is considered, and a three-dimensional finite element model is built to investigate the multi-stress degradation mechanism under multi-physical field coupling. The simulation results show that, compared with single-stress models, the proposed multi-stress coupled model can more accurately simulate the degradation process of SiC MOSFET. This provides references for improving the reliability design of power device packaging.

No-tillage with straw mulching promotes the utilization of soil nitrogen by rice under wheat-rice and oilseed rape-rice cropping systems.

Introduction: To investigate the effects of no-tillage with straw mulching on the absorption and utilization of soil nitrogen (N), fertilizer N, and straw N by rice under paddy-upland rotations. Methods: A field experiment with three cropping systems: fallow-rice rotation without straw mulching (FRN), wheat-rice rotation with wheat mulching in rice season (WRS), and oilseed rape-rice rotation with oilseed rape straw mulching in rice season (ORS) was conducted from 2015 to 2017, along with a mini-plot experiment with 15N-labeled urea and straws, which was conducted in 2017. Results: No-tillage with straw reduced rice N uptake up to 20 days after transplanting, the total amount of fertilizer N uptake of WRS and ORS rice plants was 46.33 and 61.67 kg/ha, respectively, which was 9.02 and 45.10% higher than that of FRN plants. Soil N was the main source for rice growth, followed by fertilizer N. Soil N uptake by WRS and ORS rice plants was 21.75 and 26.82% higher than that of FRN plants, accounting for 72.37 and 65.47%, respectively, of the total N accumulated in rice plants. Straw mulching increased the N utilization efficiency of tillering, panicle, and total fertilizer by 2.84-25.30%; however, base fertilizer was dependent on straw mulching. The total amount of N released from WRS and ORS straw mulching in the rice season was 34.97 and 24.82 kg/ha, respectively; however, only 3.04 and 4.82% of it was absorbed by the rice plants, accounting for only 0.62 and 0.66% of the total accumulated N. Discussion: No-tillage with straw mulching under paddy-upland rotations increased the N utilization of rice, especially for the absorption of soil N. These results provide theoretical information for the effective utilization of straw and rational N application practices in rice-based cropping systems.

Connective tissue disease-related interstitial lung disease is alleviated by tripterine through inhibition of the PI3K/Akt, apoptosis, and TNF-α signalling pathways.

Background: Interstitial lung disease (ILD) is the major cause of morbidity and mortality in patients with various rheumatic diseases. However, more interventions need to be sought. Tripterine, an extract of Tripterygium wilfordii Hook. F, has been widely studied for its powerful anti-inflammatory effect. However, its mechanism of action in treating connective tissue disease-related (CTD)-ILD remains unclear. Purpose: To investigate the mechanism of tripterine in CTD-ILD treatment by combining network pharmacology and an in vivo experiment. Methods: The related targets of tripterine were obtained after searching the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform, Comparative Toxicogenomics Database, GeneCards, Search Tool for Interacting Chemicals database, and SymMap database. Following this, Online Mendelian Inheritance in Man, GeneCards, Genebank, and DrugBank were used to screen the targets of CTD-ILD. A target-signalling pathway network was constructed using Cytoscape. Additionally, topological analysis was performed. Protein interaction analysis was performed using the STRING online analysis platform. Following this, Gene Ontology (GO) and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) signalling pathway enrichment analyses were performed. Subsequently, the molecular docking between tripterine and the core targets was verified. Finally, experimental verification was performed in bleomycin-induced model mice. Results: A total of 134 common targets and 10 core targets of tripterine, including signal transducer and activator of transcription 3, tumour necrosis factor (TNF), v-rel avian reticuloendotheliosis viral oncogene homolog A, protein kinase B (Akt) α (Akt1), mitogen-activated protein kinase (MAPK) 1, Jun transcription factor family, tumour protein 53, MAPK3, nuclear factor kappa B subunit 1, and caspase 8, were obtained. GO enrichment analysis revealed that, while treating CTD-ILD, tripterine was mainly involved in cytokine receptor binding, receptor-ligand activity, signal receptor activation, cytokine activity, protein ubiquitination, deoxyribonucleic acid transcriptase activity, etc. The KEGG pathway enrichment analysis revealed that the most significant signalling pathways were multiple viral infections and the phosphatidylinositol-3-kinase (PI3K)/Akt, TNF, and apoptosis signalling pathways. Molecular docking results revealed that tripterine had good docking activity with the core targets. Experimental studies also demonstrated that tripterine could inhibit the activation of PI3K/Akt, apoptosis, and TNF-α signalling pathways in lung tissue and significantly improve lung pathology and collagen deposition in the model mice. Conclusions: This study preliminarily revealed the potential molecular biological mechanism of tripterine while treating CTD-ILD might be related to inhibiting the PI3K/Akt, apoptosis, and TNF-α signalling pathways. Tripterygium wilfordii Hook. F. and its extract could be used clinically for treating CTD-ILD.

Trace Analysis of Emerging Virus: An Ultrasensitive ECL-Scan Imaging System for Viral Infectious Disease.

Emerging infectious diseases have brought a huge impact on human society in recent years. The outbreak of Zika virus (ZIKV) in the Americas resulted in a large number of babies born with microcephaly. More seriously, the Coronavirus Disease 2019 (COVID-19) was globally spread and caused immeasurable damages. Thus, the monitoring of highly pathogenic viruses is important to prevent and control emerging infectious diseases. Herein, a dendritic polymer probe-amplified ECL-scan imaging system was constructed to realize trace analysis of viral emerging infectious diseases. A dendritic polymer probe was employed as the efficient signal emitter component that could generate an amplified ECL signal on the integrated chip, and the signal was detected by a single-photon level charge coupled device-based ECL-scan imaging system. With this strategy, the ZIKV in a complex system of blood, urine, and saliva was detected. The results indicated that a high sensitivity of 50 copies and superior specificity were achieved. Furthermore, this strategy realized highly sensitive detection (10 copies) of the S and N protein gene sequence of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov2) and spiked pseudovirus samples. Thus, the dendritic polymer probe-amplified ECL-scan imaging system suitably met the strict clinical requirements for trace analysis of an emerging virus, and thus has the potential to serve as a paradigm for monitoring emerging infectious diseases.

Nitrogen Application Rate Affects the Accumulation of Carbohydrates in Functional Leaves and Grains to Improve Grain Filling and Reduce the Occurrence of Chalkiness.

Chalkiness, which is highly affected by nitrogen (N) management during grain filling, is critical in determining rice appearance quality and consumer acceptability. We investigated the effects of N application rates 75 (N1), 150 (N2), and 225 (N3) kg ha-1 on the source-sink carbohydrate accumulation and grain filling characteristics of two indica hybrid rice cultivars with different chalkiness levels in 2019 and 2020. We further explored the relationship between grain filling and formation of chalkiness in superior and inferior grains. In this study, carbohydrates in the functional leaves and grains of the two varieties, and grain filling parameters, could explain 66.2%, 68.0%, 88.7%, and 91.6% of the total variation of total chalky grain rate and whole chalkiness degree, respectively. They were primarily concentrated in the inferior grains. As the N fertilizer application rate increased, the chalky grain rate and chalkiness degree of both the superior and inferior grains decreased significantly. This interfered with the increase in total chalky grain rate and chalkiness. Moreover, the carbohydrate content in the functional leaves increased significantly in N2 and N3 compared with that in N1. The transfer of soluble sugar from the leaves to the grains decreased the soluble sugar and increased total starch contents, accelerated the development of grain length and width, increased grain water content, and effectively alleviated the contradiction between source and sink. These changes promoted the carbohydrate partition in superior and inferior grains, improved their average filling rate in the middle and later stages, optimized the uniformity of inferior grain fillings, and finally led to the overall reduction in rice chalkiness.