Cytoplasmic Escape of Mitochondrial DNA Mediated by Mfn2 Downregulation Promotes Microglial Activation via cGas-Sting Axis in Spinal Cord Injury.

Neuroinflammation is associated with poor outcomes in patients with spinal cord injury (SCI). Recent studies have demonstrated that stimulator of interferon genes (Sting) plays a key role in inflammatory diseases. However, the role of Sting in SCI remains unclear. In the present study, it is found that increased Sting expression is mainly derived from activated microglia after SCI. Interestingly, knockout of Sting in microglia can improve the recovery of neurological function after SCI. Microglial Sting knockout restrains the polarization of microglia toward the M1 phenotype and alleviates neuronal death. Furthermore, it is found that the downregulation of mitofusin 2 (Mfn2) expression in microglial cells leads to an imbalance in mitochondrial fusion and division, inducing the release of mitochondrial DNA (mtDNA), which mediates the activation of the cGas-Sting signaling pathway and aggravates inflammatory response damage after SCI. A biomimetic microglial nanoparticle strategy to deliver MASM7 (named MSNs-MASM7@MI) is established. In vitro, MSNs-MASM7@MI showed no biological toxicity and effectively delivered MASM7. In vivo, MSNs-MASM7@MI improves nerve function after SCI. The study provides evidence that cGas-Sting signaling senses Mfn2-dependent mtDNA release and that its activation may play a key role in SCI. These findings provide new perspectives and potential therapeutic targets for SCI treatment.

Research on the effect of environmental regulation to the green water resource efficiency in China-based on the perspectives of high pressure and low suction.

Environmental regulation with spatial spillover effect is an important way to accelerate the transformation and upgrading of modern water resources structure, and then achieve sustainable development of China's water resources. How does environmental regulation affect the GWRE to alleviate or solve China's water shortage? In this paper, the GWRE is measured based on panel data from 31 provinces in China from 2000-2020, and the impact of high pressure (low suction) and heterogeneity on GWRE by environmental regulations is explored. The results revealed that the high pressure of environmental regulation significantly promoted the improvement of GWRE, but the improvement effect of low suction power was not significant. Similar conclusions are drawn under the tests of population size-economic distance and population size-technology distance. The high pressure of market-type and autonomous-type environmental regulation has a significant effect on GWRE, while the improvement effect of command-type environmental regulation is weak. The high pressure of environmental regulation in the eastern, central, western, and northeastern regions has a decreasing effect on GWRE. It is recommended to break the principle of GDP performance appraisal, establish and improve the "green performance" evaluation system, adopt regional differentiated environmental regulation policies, and establish a modern green water resources industrial structure system.

Anthocyanin metabolism and its differential regulation in purple tea (Camellia sinensis).

Tea plants (Camellia sinensis) typically contain high-flavonoid phytochemicals like catechins. Recently, new tea cultivars with unique purple-colored leaves have gained attention. These purple tea cultivars are enriched with anthocyanin, which provides an interesting perspective for studying the metabolic flux of the flavonoid pathway. An increasing number of studies are focusing on the leaf color formation of purple tea and this review aims to summarize the latest progress made on the composition and accumulation of anthocyanins in tea plants. In addition, the regulation mechanism in its synthesis will be discussed and a hypothetical regulation model for leaf color transformation during growth will be proposed. Some novel insights are presented to facilitate future in-depth studies of purple tea to provide a theoretical basis for targeted breeding programs in leaf color.

Shading-Dependent Greening Process of the Leaves in the Light-Sensitive Albino Tea Plant 'Huangjinya': Possible Involvement of the Light-Harvesting Complex II Subunit of Photosystem II in the Phenotypic Characteristic.

The light-sensitive albino tea plant can produce pale-yellow shoots with high levels of amino acids which are suitable to process high-quality tea. In order to understand the mechanism of the albino phenotype formation, the changes in the physio-chemical characteristics, chloroplast ultrastructure, chlorophyll-binding proteins, and the relevant gene expression were comprehensively investigated in the leaves of the light-sensitive albino cultivar 'Huangjinya' ('HJY') during short-term shading treatment. In the content of photosynthetic pigments, the ultrastructure of the chloroplast, and parameters of the photosynthesis in the leaves of 'HJY' could be gradually normalized along with the extension of the shading time, resulting in the leaf color transformed from pale yellow to green. BN-PAGE and SDS-PAGE revealed that function restoration of the photosynthetic apparatus was attributed to the proper formation of the pigment-protein complexes on the thylakoid membrane that benefited from the increased levels of the LHCII subunits in the shaded leaves of 'HJY', indicating the low level of LHCII subunits, especially the lack of the Lhcb1 might be responsible for the albino phenotype of the 'HJY' under natural light condition. The deficiency of the Lhcb1 was mainly subject to the strongly suppressed expression of the Lhcb1.x which might be modulated by the chloroplast retrograde signaling pathway GUN1 (GENOMES UNCOUPLED 1)-PTM (PHD type transcription factor with transmembrane domains)-ABI4 (ABSCISIC ACID INSENSITIVE 4).

Anticarcinogenic potentials of tea catechins.

Catechins are a cluster of polyphenolic bioactive components in green tea. Anticarcinogenic effects of tea catechins have been reported since the 1980s, but it has been controversial. The present paper reviews the advances in studies on the anticarcinogenic activities of tea and catechins, including epidemiological evidence and anticarcinogenic mechanism. Tea catechins showed antagonistic effects on many cancers, such as gynecological cancers, digestive tract cancers, incident glioma, liver and gallbladder cancers, lung cancer, etc. The mechanism underlying the anticarcinogenic effects of catechins involves in inhibiting the proliferation and growth of cancer cells, scavenging free radicals, suppressing metastasis of cancer cells, improving immunity, interacting with other anticancer drugs, and regulating signaling pathways. The inconsistent results and their causes are also discussed in this paper.

Management for lumbar spinal stenosis: Protocol for a network meta-analysis and systematic review.

INTRODUCTION: Lumbar spinal stenosis (LSS) is caused by structural changes of the spine, which lead to several severe symptoms, including back pain, leg pain, numbness and tingling in the legs, as well as reduced physical function. However, there is little evidence suggesting whether a patient with LSS should be treated with surgery. If surgery is recommended, which type of surgery benefits the patient most? To answer these questions, we will conduct a network meta-analysis and a systematic review to compare surgical and nonsurgical interventions in terms of efficacy as well as safety in adult patients with LSS. METHODS AND ANALYSIS: We will search the PubMed, Cochrane library, and EMBASE databases for articles published prior to October 10, 2019. We will search for randomized controlled trials assessing surgical and nonsurgical interventions for adult patients with degenerative LSS without any language restrictions. The primary outcome measures will be pain and disability. The secondary outcomes will include adverse events (number of events or number of people with each type of adverse event), reoperations, complications, blood loss and operation time. We will obtain the full texts of the potentially relevant studies and independently assess them. The quality of evidence will be evaluated according to the Grading of Recommendations Assessment, Development and Evaluation framework. A random-effects network meta-analysis will be performed to analyze all the evidence under the frequentist framework, and the ranking results will be presented. We will generate plots depicting the network geometry using Stata. The network meta-analysis will be performed according to the Bayesian framework. Ethics and dissemination Ethics approval is not required. The research will be published in a peer-reviewed journal.

SiBaoChongCao exhibited anti-fatigue activities and ameliorated cancer cachexia in mice.

SiBaoChongCao (SBCC) is a functional food product containing fermentation of Acremonium terricola belonging to the Cordyceps genus. SBCC at 1 and 2 g kg-1 for 20 days exhibited anti-fatigue activities such as increasing exhaustive swimming and running time of mice and increasing the strength of muscle. The increased muscle endurance in SBCC-treated mice might be related to enhancement of muscle cell growth and differentiation and improvement of muscle response to exercise training, as shown by an increase in muscle cross-sectional area and elevation of MHC, MyoD, MyoG and PGC-1α levels. And, SBCC at 1.5 g kg-1 could ameliorate cancer-related cachexia such as ameliorating decrease in body temperature and inhibiting fat tissue atrophy. The anti-cachexia effects of SBCC might be related to inhibition of inflammatory cytokine IL-6 secretion and suppression of over-lipolysis and lipid over-utilization through inhibiting the activation of AMPK and p38 MAPK and down-regulating the level of UCP1.

Ginsenoside Rh2 enhances the antitumor immunological response of a melanoma mice model.

The treatment of malignant tumors following surgery is important in preventing relapse. Among all the post-surgery treatments, immunomodulators have demonstrated satisfactory effects on preventing recurrence according to recent studies. Ginsenoside is a compound isolated from panax ginseng, which is a famous traditional Chinese medicine. Ginsenoside aids in killing tumor cells through numerous processes, including the antitumor processes of ginsenoside Rh2 and Rg1, and also affects the inflammatory processes of the immune system. However, the role that ginsenoside serves in antitumor immunological activity remains to be elucidated. Therefore, the present study aimed to analyze the effect of ginsenoside Rh2 on the antitumor immunological response. With a melanoma mice model, ginsenoside Rh2 was demonstrated to inhibit tumor growth and improved the survival time of the mice. Ginsenoside Rh2 enhanced T-lymphocyte infiltration in the tumor and triggered cytotoxicity in spleen lymphocytes. In addition, the immunological response triggered by ginsenoside Rh2 could be transferred to other mice. In conclusion, the present study provides evidence that ginsenoside Rh2 treatment enhanced the antitumor immunological response, which may be a potential therapy for melanoma.

miR-15a and miR-16-1 downregulate CCND1 and induce apoptosis and cell cycle arrest in osteosarcoma.

Osteosarcoma, the most common primary tumor of the bones, causes many deaths due to its rapid proliferation and drug resistance. Recent studies have shown that cyclin D1 plays a key regulatory role during cell proliferation, and non-coding microRNAs (miRNAs) act as crucial modulators of cyclin D1 (CCND1). The aim of the current study was to determine the role of miRNAs in controlling CCND1 expression and inducing cell apoptosis. CCND1 has been found to be a target of miR-15a and miR-16-1 through analysis of complementary sequences between microRNAs and CCND1 mRNA. The upregulation of miR-15a and miR-16-1 in the cell line SOSP-9607 induces apoptosis and cell cycle arrest. Osteosarcoma cells transfected with miR-15a and miR-16-1 show slower proliferation curves. Moreover, the transcription of CCND1 is suppressed by miR-15a and miR-16-1 via direct binding to the CCND1 3'-untranslated region (3'-UTR). The data presented here demonstrate that the CCND1 contributes to osteosarcoma cell proliferation, suggesting that repression of CCND1 by miR-15a and miR-16-1 could be used for osteosarcoma therapy.

Point-of-care test of heart-type fatty acid-binding protein for the diagnosis of early acute myocardial infarction.

AIM: To investigate the efficacies of point-of-care test of heart-type fatty-acid binding protein (H-FABP) and its combinations with the conventional biomarkers in the diagnosis of early acute myocardial infarction (AMI). METHODS: 227 patients suspected of AMI were consecutively recruited in two centers. Biomarkers including H-FABP, myoglobin (MYO), creatine kinase-myocardial band (CK-MB) and cardiac troponin T (cTnT) were determined simultaneously at admission. AMI was defined according to the universal definition of myocardial infarction. Chi-Square test was adopted for the analysis. RESULTS: In patients presenting within 12 h of symptom onset, the sensitivity of H-FABP[93.0% (95% CI: 86.6%-96.9%)] was significantly higher than that of initial CK-MB [67.5% (95% CI: 58.1%-76.0%), P<0.0001], cTnT [69.3% (95%CI: 60.0%-77.6%), P<0.0001] and MYO [68.6% (95% CI: 54.1%-80.9%), P<0.05]. The negative predictive value of H-FABP [92.8% (95%CI: 86.3%-96.8%)] was significantly higher than that of initial CK-MB [74.7% (95% CI: 66.8%-81.5%), P<0.001] and cTnT [75.9% (95% CI: 68.1%-82.6%), P<0.001]. The sensitivity of H-FABP+cTnT combination [94.7% (95% CI: 88.9%-98.0%)] was significantly higher than that of admission cTnT [69.3% (95% CI: 60.0%-77.6%), P<0.0001], CK-MB+cTnT [75.4% (95% CI: 66.5%-83.0%), P<0.0001] and MYO+CK-MB+cTnT [74.5% (95% CI: 60.4%-85.7%), P<0.05]. The negative predictive value of H-FABP+cTnT [94.5% (95% CI: 88.4%-98.0%] was significantly higher than that of initial cTnT [75.9% (95% CI: 68.1%-82.6%), P<0.001] and CK-MB+cTnT [79.1% (95% CI: 71.2%-85.6%), P<0.001]. Subgroup analysis showed that the superiorities of both the sensitivities and the negative predictive values of H-FABP and H-FABP+cTnT combination occurred only in patients who presented within 6 h of the symptom onset. CONCLUSION: Point-of-care test of H-FABP can be used as a valuable biomarker to detect or exclude an early-stage AMI. Combining H-FABP and cTnT provides the best performance for early AMI diagnosis.

[Effects of cadmium on rice seed germination].

With 319 rice varieties as test objects, this paper studied the effects of cadmium on their seed germination. The results showed that after treated with 10 mg x L(-1) of Cd2+, seed germination rate was less affected, but root growth was restrained evidently. Cadmium had more serious impact on root than on sprout. Different rice varieties had different germination responses to Cd2+, with the sequence of conventional rice (Japonica rice) > hybrid rice (Indianica rice) > conventional rice (Indianica rice). The root length and number of two-line sterilities were restrained more strongly than those of three-line sterilities. Based on their responses to Cd2+, the test 319 varieties were clustered into 3 types, i.e., endurant type, medium type, and sensitive type.

Study on the supramolecular systems of 5-(2-hydroxy phenyl)-10,15,20-tris (4-methoxy phenyl) porphyrin with cyclodextrins.

In neutral phosphate buffer solutions of pH 7.4, the inclusive complexation of 5-(2-hydroxy phenyl)-10,15,20-tris(4-methoxy phenyl) porphyrin (o-HTPP) with alpha-cyclodextrin (alpha-CD), beta-CD, heptakis (2,3,6-tri-O-methyl)-beta-CD (TM-beta-CD), SBE-beta-CD, HP-beta-CD and gamma-CD has been examined by means of UV-vis and fluorescence spectroscopy. The formation of inclusion complexes has been confirmed on the base of changes of spectroscopy properties. The o-HTPP forms 1:2 inclusion complexes with TM-beta-CD and 1:1 inclusion complexes with the other five cyclodextrins. The formation constants (K) of o-HTPP for the formation of the inclusion complexes have been estimated from the absorbance and fluorescence intensity changes in neutral phosphate buffer solutions. The K value (2.89x10(7)), which is the formation constant for the formation of the 1:2 inclusion supramolecular, is nearly 10(4) times than those of the 1:1 inclusion complexes. Compared to the other five cyclodextrins, the strongest inclusion ability of TM-beta-CD can be explained that the hydrogen bond plays significant role in the inclusion process. UV-vis experiments also showed that the cavity of TM-beta-CD causes the transform of the state of o-HTPP. In addition (1)H NMR data and 2D-ROSEY NMR spectra support the inclusion conformation of the o-HTPP-CD supramolecular system, indicating the interaction mechanism of inclusion processes.