Human umbilical cord-derived mesenchymal stem cell transplantation supplemented with curcumin improves the outcomes of ischemic stroke via AKT/GSK-3ß/ß-TrCP/Nrf2 axis.

BACKGROUND: Human umbilical cord-derived mesenchymal stem cell (hUC-MSC) engraftment is a promising therapy for acute ischemic stroke (AIS). However, the harsh ischemic microenvironment limits the therapeutic efficacy of hUC-MSC therapy. Curcumin is an anti-inflammatory agent that could improve inflammatory microenvironment. However, whether it enhances the neuroprotective efficacy of hUC-MSC transplantation is still unknown. In the present study, we investigated the therapeutic efficacy and the possible mechanism of combined curcumin and hUC-MSC treatment in AIS. METHODS: Middle cerebral artery occlusion (MCAO) mice and oxygen glucose deprivation (OGD) microglia were administrated hUC-MSCs with or without curcumin. Neurological deficits assessment, brain water content and TTC were used to assess the therapeutic effects of combined treatment. To elucidate the mechanism, MCAO mice and OGD microglia were treated with AKT inhibitor MK2206, GSK3ß activator sodium nitroprusside (SNP), GSK3ß inhibitor TDZD-8 and Nrf2 gene knockout were used. Immunofluorescence, flow cytometric analysis, WB and RT-PCR were used to evaluate the microglia polarization and the expression of typical oxidative mediators, inflammatory cytokines and the AKT/GSK-3ß/ß-TrCP/Nrf2 pathway protein. RESULTS: Compared with the solo hUC-MSC-grafted or curcumin groups, combined curcumin-hUC-MSC therapy significantly improved the functional performance outcomes, diminished the infarct volumes and the cerebral edema. The combined treatment promoted anti-inflammatory microglia polarization via Nrf2 pathway and decreased the expression of ROS, oxidative mediators and pro-inflammatory cytokines, while elevating the expression of the anti-inflammatory cytokines. Nrf2 knockout abolished the antioxidant stress and anti-inflammation effects mediated with combined treatment. Moreover, the combined treatment enhanced the phosphorylation of AKT and GSK3ß, inhibited the ß-TrCP nucleus translocation, accompanied with Nrf2 activation in the nucleus. AKT inhibitor MK2206 activated GSK3ß and ß-TrCP and suppressed Nrf2 phosphorylation in nucleus, whereas MK2206 with the GSK3ß inhibitor TDZD-8 reversed these phenomena. Furthermore, combined treatment followed by GSK3ß inhibition with TDZD-8 restricted ß-TrCP nucleus accumulation, which facilitated Nrf2 expression. CONCLUSIONS: We have demonstrated that combined curcumin-hUC-MSC therapy exerts anti-inflammation and antioxidant stress efficacy mediated by anti-inflammatory microglia polarization via AKT/GSK-3ß/ß-TrCP/Nrf2 axis and an improved neurological function after AIS.

MitoQ attenuates brain damage by polarizing microglia towards the M2 phenotype through inhibition of the NLRP3 inflammasome after ICH.

Microglial phenotype plays an important role in secondary injury after intracerebral haemorrhage (ICH), with M1 microglia promoting inflammatory injury and M2 microglia inhibiting neuroinflammation and promoting haematoma absorption. However, there is no effective intervention for regulating the phenotypic transformation of microglia after ICH. This study aimed to elucidate the protective effect of MitoQ, a selective mitochondrial ROS antioxidant, against microglial M1 state polarization and secondary brain injury. The in vivo data showed that MitoQ attenuated neurological deficits and decreased inflammation, oedema and haematoma volume after ICH. In addition, MitoQ decreased the expression of M1 markers and increased the expression of M2 markers both in vivo and in vitro after ICH. Mechanistically, MitoQ blocked overproduction of mitochondrial ROS and activation of the NLRP3 inflammasome in FeCl2-treated microglia. Moreover, NLRP3 siRNA shifted FeCl2-treated microglia from the M1 to the M2 cells, revealing that MitoQ-induce polarization states may be mediated by the mitochondrial ROS/NLRP-3 pathway. In summary, MitoQ alleviates secondary brain injury and accelerates haematoma resolution by shifting microglia towards the M2 phenotype after ICH.

Male sterile 305 Mutation Leads the Misregulation of Anther Cuticle Formation by Disrupting Lipid Metabolism in Maize.

The anther cuticle, which is mainly composed of lipid polymers, functions as physical barriers to protect genetic material intact; however, the mechanism of lipid biosynthesis in maize (Zea mays. L.) anther remains unclear. Herein, we report a male sterile mutant, male sterile 305 (ms305), in maize. It was shown that the mutant displayed a defective anther tapetum development and premature microspore degradation. Three pathways that are associated with the development of male sterile, including phenylpropanoid biosynthesis, biosynthesis of secondary metabolites, as well as cutin, suberine, and wax biosynthesis, were identified by transcriptome analysis. Gas chromatography-mass spectrometry disclosed that the content of cutin in ms305 anther was significantly lower than that of fertile siblings during the abortion stage, so did the total fatty acids, which indicated that ms305 mutation might lead to blocked synthesis of cutin and fatty acids in anther. Lipidome analysis uncovered that the content of phosphatidylcholine, phosphatidylserine, diacylglycerol, monogalactosyldiacylglycerol, and digalactosyldiacylglycerol in ms305 anther was significantly lower when compared with its fertile siblings, which suggested that ms305 mutation disrupted lipid synthesis. In conclusion, our findings indicated that ms305 might affect anther cuticle and microspore development by regulating the temporal progression of the lipidome in maize.

Curcumin attenuates blood-brain barrier disruption after subarachnoid hemorrhage in mice.

BACKGROUND: Early brain injury, one of the most important mechanisms underlying subarachnoid hemorrhage (SAH), comprises edema formation and blood-brain barrier (BBB) disruption. Curcumin, an active extract from the rhizomes of Curcuma longa, alleviates neuroinflammation by as yet unknown neuroprotective mechanisms. In this study, we examined whether curcumin treatment ameliorates SAH-induced brain edema and BBB permeability changes, as well as the mechanisms underlying this phenomenon. METHODS: We induced SAH in mice via endovascular perforation, administered curcumin 15 min after surgery and evaluated neurologic scores, brain water content, Evans blue extravasation, Western blot assay results, and immunohistochemical analysis results 24 h after surgery. RESULTS: Curcumin significantly improved neurologic scores and reduced brain water content in treated mice compared with SAH mice. Furthermore, curcumin decreased Evans blue extravasation, matrix metallopeptidase-9 expression, and the number of Iba-1-positive microglia in treated mice compared with SAH mice. At last, curcumin treatment increased the expression of the tight junction proteins zonula occludens-1 and occludin in treated mice compared with vehicle-treated and sample SAH mice. CONCLUSIONS: We demonstrated that curcumin inhibits microglial activation and matrix metallopeptidase-9 expression, thereby reducing brain edema and attenuating post-SAH BBB disruption in mice.

[Potato Spectrum and the Digital Image Feature Parameters on the Response of the Nitrogen Level and Its Application].

In order to know the potatoes nitrogen situation rapidly and accurately, promoting the efficient use of nitrogen fertilizer on the potatoes. Using the feature of portable hyperspectral spectrometer, digital cameras and SPAD-502 chlorophyll meter to abtain the potato digital indicators, leaf spectral and SPAD. Analysing the change status of digital indicators, leaf spectral index, SPAD and production of potatoes under different nitrogen levels in two key periods. Analysing the correlation between canopy image, leaf spectral and SPAD and production, with SPAD as auxiliary validation index, nitrogen fertilizer efficiency evaluation of yield to make sure potato canopy image under the most economic nitrogen application levels and leaf spectral's critical value to explore the methods of nitrogen nutrition diagnosis quickly and simply. The results show: (1)With nitrogen levels increased, potato tuber formation stage and tuber bulking stage leaf spectral reflectance is the emergence of the "red shift" phenomenon, and the red edge parameters REP, Lwidth, FD_Max increased, Lo decreased. (2)With the nitrogen levels increased, potatoes tuber formation stage and tuber bulking stage digital indicators G/B, (G-B)/(R+G+B) decreased gradually, B/(R+G+B) increased gradually. (3) with the increase of nitrogen application rate SPAD is increased.It is obvious low nitrogen levels increase production with nitrogen increased. It is not obvious the high level of nitrogen stimulation effect. Potato canopy image, leaf spectral and red edge parameters have good correlation with SPAD value and productions, establishing the index evaluation of nitrogen nutrition abundance or lack of quantitative standard of potatoes. Indicating digital image and spectrum technology to nitrogen nutrition diagnosis of potatoes is feasible, provide research ideas and technical support for the potato accurate monitoring of nitrogen nutrition.

Valproic Acid Arrests Proliferation but Promotes Neuronal Differentiation of Adult Spinal NSPCs from SCI Rats.

Although the adult spinal cord contains a population of multipotent neural stem/precursor cells (NSPCs) exhibiting the potential to replace neurons, endogenous neurogenesis is very limited after spinal cord injury (SCI) because the activated NSPCs primarily differentiate into astrocytes rather than neurons. Valproic acid (VPA), a histone deacetylase inhibitor, exerts multiple pharmacological effects including fate regulation of stem cells. In this study, we cultured adult spinal NSPCs from chronic compressive SCI rats and treated with VPA. In spite of inhibiting the proliferation and arresting in the G0/G1 phase of NSPCs, VPA markedly promoted neuronal differentiation (ß-tubulin III(+) cells) as well as decreased astrocytic differentiation (GFAP(+) cells). Cell cycle regulator p21(Cip/WAF1) and proneural genes Ngn2 and NeuroD1 were increased in the two processes respectively. In vivo, to minimize the possible inhibitory effects of VPA to the proliferation of NSPCs as well as avoid other neuroprotections of VPA in acute phase of SCI, we carried out a delayed intraperitoneal injection of VPA (150 mg/kg/12 h) to SCI rats from day 15 to day 22 after injury. Both of the newborn neuron marker doublecortin and the mature neuron marker neuron-specific nuclear protein were significantly enhanced after VPA treatment in the epicenter and adjacent segments of the injured spinal cord. Although the impaired corticospinal tracks had not significantly improved, Basso-Beattie-Bresnahan scores in VPA treatment group were better than control. Our study provide the first evidence that administration of VPA enhances the neurogenic potential of NSPCs after SCI and reveal the therapeutic value of delayed treatment of VPA to SCI.

Curcumin improves neural function after spinal cord injury by the joint inhibition of the intracellular and extracellular components of glial scar.

BACKGROUND: Spinal cord injury (SCI) is characterized by a high rate of disability and imposes a heavy burden on society and patients. SCI can activate glial cells and lead to swelling, hyperplasty, and reactive gliosis, which can severely reduce the space for nerve growth. Glial cells can secrete a large amount of extracellular inhibitory components, thus altering the microenvironment of axon growth. Both these factors seriously impede nerve regeneration. In the present study, we investigate whether curcumin (cur), a phytochemical compound with potent anti-inflammatory effect, plays a role in the repair of SCI. MATERIALS AND METHODS: We established a rat model of SCI and treated the animals with different concentrations of cur. Using behavioral assessment, immunohistochemistry, real-time polymerase chain reaction, Western blotting, and enzyme-linked immunosorbent assay, we detected the intracellular and extracellular components of glial scar and related cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, nuclear factor (NF)-κb, transforming growth factor (TGF)-ß1, TGF-ß2, and sex determining region Y-box (SOX)-9. RESULTS: We found that cur inhibited the expression of proinflammatory cytokines, such as TNF-α, IL-1ß, and NF-κb; reduced the expression of the intracellular components glial fibrillary acidic protein through anti-inflammation; and suppressed the reactive gliosis. Also, cur inhibited the generation of TGF-ß1, TGF-ß2, and SOX-9; decreased the deposition of chondroitin sulfate proteoglycan by inhibiting the transforming growth factors and transcription factor; and improved the microenvironment for nerve growth. Through the joint inhibition of the intracellular and extracellular components of glial scar, cur significantly reduced glial scar volume and improved the Basso, Beattie, and Bresnahan locomotor rating and axon growth. CONCLUSIONS: Our data support a role for curcumin in promoting neural function recovery after SCI by the joint inhibition of the intracellular and extracellular components of glial scar, providing an important strategy for treating SCI.

Hyperbaric oxygen therapy ameliorates acute brain injury after porcine intracerebral hemorrhage at high altitude.

INTRODUCTION: Intracerebral hemorrhage (ICH) at high altitude is not well understood to date. This study investigates the effects of high altitude on ICH, and examines the acute neuroprotection of hyperbaric oxygen (HBO) therapy against high-altitude ICH. METHODS: Minipigs were placed in a hypobaric chamber for 72 h before the operation. ICH was induced by an infusion of autologous arterial blood (3 ml) into the right basal ganglia. Animals in the high-altitude ICH group received HBO therapy (2.5 ATA for 60 min) 30 min after ICH. Blood gas, blood glucose and brain tissue oxygen partial pressure (PbtO2) were monitored continuously for animals from all groups, as were microdialysis products including glucose, lactate, pyruvate and glutamate in perihematomal tissue from 3 to 12 h post-ICH. RESULTS: High-altitude ICH animals showed significantly lower PbtO2, higher lactate/pyruvate ratio (LPR) and glutamate levels than low-altitude ICH animals. More severe neurological deficits, brain edema and neuronal damage were also observed in high-altitude ICH. After HBO therapy, PbtO2 was significantly increased and LPR and glutamate levels were significantly decreased. Brain edema, neurological deficits and neuronal damage were also ameliorated. CONCLUSIONS: The data suggested a more serious disturbance of tissue oxygenation and cerebral metabolism in the acute stage after ICH at high altitude. Early HBO treatment reduced acute brain injury, perhaps through a mechanism involving the amelioration of the derangement of cerebral oxygenation and metabolism following high-altitude ICH.

Curcumin attenuates acute inflammatory injury by inhibiting the TLR4/MyD88/NF-κB signaling pathway in experimental traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) initiates a neuroinflammatory cascade that contributes to substantial neuronal damage and behavioral impairment, and Toll-like receptor 4 (TLR4) is an important mediator of thiscascade. In the current study, we tested the hypothesis that curcumin, a phytochemical compound with potent anti-inflammatory properties that is extracted from the rhizome Curcuma longa, alleviates acute inflammatory injury mediated by TLR4 following TBI. METHODS: Neurological function, brain water content and cytokine levels were tested in TLR4⁻/⁻ mice subjected to weight-drop contusion injury. Wild-type (WT) mice were injected intraperitoneally with different concentrations of curcumin or vehicle 15 minutes after TBI. At 24 hours post-injury, the activation of microglia/macrophages and TLR4 was detected by immunohistochemistry; neuronal apoptosis was measured by FJB and TUNEL staining; cytokines were assayed by ELISA; and TLR4, MyD88 and NF-κB levels were measured by Western blotting. In vitro, a co-culture system comprised of microglia and neurons was treated with curcumin following lipopolysaccharide (LPS) stimulation. TLR4 expression and morphological activation in microglia and morphological damage to neurons were detected by immunohistochemistry 24 hours post-stimulation. RESULTS: The protein expression of TLR4 in pericontusional tissue reached a maximum at 24 hours post-TBI. Compared with WT mice, TLR4⁻/⁻ mice showed attenuated functional impairment, brain edema and cytokine release post-TBI. In addition to improvement in the above aspects, 100 mg/kg curcumin treatment post-TBI significantly reduced the number of TLR4-positive microglia/macrophages as well as inflammatory mediator release and neuronal apoptosis in WT mice. Furthermore, Western blot analysis indicated that the levels of TLR4 and its known downstream effectors (MyD88, and NF-κB) were also decreased after curcumin treatment. Similar outcomes were observed in the microglia and neuron co-culture following treatment with curcumin after LPS stimulation. LPS increased TLR4 immunoreactivity and morphological activation in microglia and increased neuronal apoptosis, whereas curcumin normalized this upregulation. The increased protein levels of TLR4, MyD88 and NF-κB in microglia were attenuated by curcumin treatment. CONCLUSIONS: Our results suggest that post-injury, curcumin administration may improve patient outcome by reducing acute activation of microglia/macrophages and neuronal apoptosis through a mechanism involving the TLR4/MyD88/NF-κB signaling pathway in microglia/macrophages in TBI.

Curcumin increased the differentiation rate of neurons in neural stem cells via wnt signaling in vitro study.

BACKGROUND: The objective of the present study was to clarify the relationship between the neuroprotective effects of curcumin and the classical wnt signaling pathway. METHOD: Using Sprague-Dawley rats at a gestational age of 14.5 d, we isolated neural stem cells from the anterior two-thirds of the fetal rat brain. The neural stem cells were passaged three times using the half media replacement method and identified using cellular immunofluorescence. After passaging for three generations, we cultured cells in media without basic fibroblast growth factor and epidermal growth factor. Then we treated cells in five different ways, including a blank control group, a group treated with IWR1 (10 µmol/L), a group treated with curcumin (500 nmol/L), a group treated with IWR1 + curcumin, and a group treated with dimethyl sulfoxide (10 µmol/L). We then measured the protein and RNA expression levels for wnt3a and ß-catenin using Western blotting and Reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Western-blotting: after the third generation of cells had been treated for 72 h, we observed that wnt3a and ß-catenin expression was significantly increased in the group receiving 500 nmol/L curcumin but not in the other groups. Furthermore, cells in the IWR1-treated group showed decreased wnt3a and ß-catenin expression, and wnt3a and ß-catenin was also decreased in the IWR1 + 500 nmol/L curcumin group. No obvious change was observed in the dimethyl sulfoxide group. RT-PCR: RT-PCR showed similar changes to those observed with the Western blotting experiments. CONCLUSIONS: Our study suggests that curcumin can activate the wnt signaling pathway, which provides evidence that curcumin exhibits a neuroprotective effect through the classical wnt signaling pathway.

Optimization of high-pressure ultrasonic-assisted simultaneous extraction of six major constituents from Ligusticum chuanxiong rhizome using response surface methodology.

High-pressure ultrasound-assisted extraction technology was applied to extract ferulic acid, senkyunolide I, senkyunolide H, senkyunolide A, ligustilide and levistolide A from Ligusticum chuanxiong rhizomes. Seven independent variables, including solvent type, pressure, particle size, liquid-to-solid ratio, extraction temperature, ultrasound power, and extraction time were examined. Response Surface Methodology (RSM) using a Central Composite Design (CCD) was employed to optimize the experimental conditions (extraction temperature, ultrasonic power, and extraction time) on the basis of the results of single factor tests for the extraction of these six major components in L. chuanxiong rhizomes. The experimental data were fitted to a second-order polynomial equation using multiple regression analysis and were also examined using appropriate statistical methods. The best extraction conditions were as follows: extraction solvent: 40% ethanol; pressure: 10 MPa; particle size: 80 mesh; liquid-to-solid ratio: 100:1; extraction temperature: 70 °C; ultrasonic power, 180 W; and extraction time, 74 min.

[Quantitative determination of 5 active ingredients in different harvest periods of Ligusticum chuanxiong by HPLC].

A simple and quick method is described for the determination of ferulic acid, senkyunolide I, senkyunolide H, senkyunolide A and ligustilide in rhizomes of Ligusticum chuanxiong. The 5 active ingredients in the sample was extracted using 40% ethanol and analyzed by reversed-phase high performance liquid chromatography (HPLC). Chromatography separation was performed using Agilent 1100 series HPLC system with a Symmetry C18 column and gradient elution with a mixture of three solvents : solvent A, acetonitrile, solvent B, methanol and solvent C, 1% aqueous acetic acid, 0 min to 5 min A: B: C 20: 40: 40, 5 min to 30 min A: B: C 60 to 100 : 0 : 40 to 0. The effluent was monitored using a VWD detector set at 321 nm (0-4.3 min) and 275 nm (4.31-30 min). The flow rate was set at 1 mL x min(-1) and the injection volume was 10 microL. The column temperature was maintained at 35 degrees C. The calibration curve was linear (r > or = 0.99) over the tested ranges. The average recovery was 94.44%-103.1% (n = 6). The method has been successfully applied to the analysis in different harvest periods of L. chuanxiong samples. In this paper, single-factor randomized block design to study the 5 components content of L. chuanxiong on ten collecting stages. For the L. chuanxiong collected from April 15th to May 30rd, the content of 5 ingredients increased primarily, and then decreased. Determine the appropriate harvest time has important significance to the promotion of the quality of L. chuanxiong.

Experimental high-altitude intracerebral hemorrhage in minipigs: histology, behavior, and intracranial pressure in a double-injection model.

BACKGROUND: Specific pathophysiological mechanism in intracerebral hemorrhage (ICH) at high altitude is unclear, and at present, there is no relevant and suitable animal model. METHODS: A hypobaric chamber was used to simulate an altitude of 4,000 m. Autologous arterial blood (3 ml) was slowly infused into the right basal ganglia of minipigs by a double-injection method for producing ICH. RESULTS: The intracranial pressure and neurological score of the high-altitude group were significantly higher than those of the low-altitude (plain) group. The brain water contents and pathological lesions of perihematoma tissue were more severe in the high-altitude group. CONCLUSIONS: The injury resulting from ICH at high altitude was more severe than that in the plain group. This model was able to produce controllable and reproducible hematomas and visible neurological deficits, which may be useful for future studies of the pathophysiology and functional rehabilitation of high-altitude ICH disease.

Bibliometric analysis of tumor necrosis factor in post-stroke neuroinflammation from 2003 to 2021.

Objective: Tumor necrosis factor (TNF), a crucial cytokine, has important research value in post-stroke neuroinflammation (PSN). We analyzed the studies that have been conducted in this area and used bibliometric methods to predict research hotspots and identify trends regarding TNF in PSN. Methods: Publications were accessed at the Science Citation Index Expanded 1975-2021 (SCI expanded), Web of Science Core Collection (WoSCC), on May 1, 2022. Additionally, software such as CiteSpace and VOSviewer were utilized for bibliometric analyses. Results: In total, 1391 original articles and reviews on TNF in PSN published from 2003 to 2021 were identified. An upward trend was observed in the number of publications on TNF in PSN. These publications were primarily from 57 countries and 1446 institutions, led by China and the United States with China leading the number of publications (NP) and the US with the number of citations (NC). The League of European Research Universities (LERU) and Journal of Neuroinflammation, respectively were the most prolific branches and journals. Zhang, John H. published the most papers and Finsen, Bente had the most cited papers. One paper by Kettenmann, H. published in 2011 reached the highest level of Global Citation Score (GCS). The keyword co-occurrence and reference co-citation analyses suggest that poststroke therapy and potential mechanistic pathways are important topics related to PSN in recent years. Reference burst detection suggests new burst hotspots after 2015, focusing on pathway modulation and discovery of therapeutic targets, suggesting a substantial development in the study of TNF in PSN research. Conclusion: The present bibliometric analysis shows a continuous trend of increasing literature related to TNF in PSN, and shows that TNF plays an important role in PSN involves multiple immune mechanisms and may contribute as a potential target for neuroprotective therapeutics after stroke. Prior to 2011, most of the research was focused on discovering the specific role of TNF in PSN, and in recent years studies have mainly targeted the exploration of the signaling pathways. Future research prospects may lie in finding key therapeutic targets in pathway of TNF in PSN.

Cultivar differences in carbon and nitrogen accumulation, balance, and grain yield in maize.

The balance of carbon (C) and nitrogen (N) metabolism influences plant growth and development as well as yield. A two-year field experiment was conducted in a hilly region in southwest China in 2019-2020 to investigate the correlation between the accumulation and balance of C and N, as well as the grain yield of maize cultivars with contrasting N efficiencies. Using Zhenghong 311 (ZH 311) and Xianyu 508 (XY 508) as research sources, the differences in C and N accumulation and balance in maize cultivars with contrasting N efficiencies were compared to analyze the correlation between the accumulation and balance of C and N with grain yield. According to the results, the ZH 311 cultivar had higher C and N accumulation in each stage and grain yield than the XY 508 cultivar, while the C/N ratio in each stage and organ was significantly lower in ZH 311 than in XY 508, with the greatest difference occurring in the silking stage and leaf, indicating that the N-efficient cultivar ZH 311 had evident advantages in accumulation and balance of C and N and grain yield than the N-inefficient cultivar XY 508. Moreover, the C and N accumulation and grain yield increased significantly with N application, while the C/N ratio in each stage and organ decreased significantly with N application, but the differences between ZH 311 and XY 508 increased first and then decreased with the increase of N level, the optimum N level when obtaining the highest grain yield of ZH 311 (273.21 kg ha-1) was significantly lower than that of XY 508 (355.88 kg ha-1). Furthermore, grain yield was positively correlated with C (R 2 = 0.9251) and N (R 2 = 0.9033) accumulation, affected by pre-anthesis N (R 2 = 0.9198) and post-anthesis C (R 2 = 0.8632) accumulation, and negatively correlated with the C/N ratio (R 2 = 0.7664), with the highest correlation between grain yield and the C/N ratio in silking stage (R 2 = 0.7984) and leaf (R 2 = 0.7616). In conclusion, the N-efficient cultivar ZH 311 could better coordinate the C and N balance of the plant, especially the C and N balance in the silking stage and leaf, promote photosynthetic product storage and transport, prolong the leaf function period, and make the pre-anthesis and post-anthesis C and N accumulation of ZH 311 significantly higher than those of XY 508, allowing higher grain yields.

Case Report: Diffuse Cerebral Microbleeds in Cerebral Autosomal Recessive Arteriopathy With Subcortical Infarcts and Leukoencephalopathy.

Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a hereditary cerebral small vascular disease caused by a homozygous mutation in the high-temperature requirement A serine peptidase 1 (HTRA1) gene. Cerebral microbleeds (CMBs) are increasingly being recognized as neuroimaging findings occurring with cerebrovascular disease and have different etiologies. Mild to moderate CMBs are not unusual in CARASIL, and they are observed to affect cortical and subcortical structures; in contrast, diffuse CMBs, especially in the cerebellum, are rare. In this case, we report a novel mutation of HTRA1 in a 43-year-old woman whose imaging indicated multiple CMBs in all lobes, brain stem, and cerebellum. The amount and location of CMBs vary in CARASIL cases, and the potential cause is not fully understood. This study revealed that specific imaging findings of this patient may be related to a new genetic mutation.

Adenosine A2A Receptor Suppressed Astrocyte-Mediated Inflammation Through the Inhibition of STAT3/YKL-40 Axis in Mice With Chronic Cerebral Hypoperfusion-induced White Matter Lesions.

White matter lesions are an important pathological manifestation of cerebral small vessel disease, with inflammation playing a pivotal role in their development. The adenosine A2a receptor (ADORA2A) is known to inhibit the inflammation mediated by microglia, but its effect on astrocytes is unknown. Additionally, although the level of YKL-40 (expressed mainly in astrocytes) has been shown to be elevated in the model of white matter lesions induced by chronic cerebral hypoperfusion, the specific regulatory mechanism involved is not clear. In this study, we established in vivo and in vitro chronic cerebral hypoperfusion models to explore whether the ADORA2A regulated astrocyte-mediated inflammation through STAT3/YKL-40 axis and using immunohistochemical, western blotting, ELISA, PCR, and other techniques to verify the effect of astrocytes ADORA2A on the white matter injury. The in vivo experiments showed that activation of the ADORA2A decreased the expression of both STAT3 and YKL-40 in the astrocytes and alleviated the white matter injury, whereas its inhibition had the opposite effects. Similarly, ADORA2A inhibition significantly increased the expression of STAT3 and YKL-40 in astrocytes in vitro, with more proinflammatory cytokines being released by astrocytes. STAT3 inhibition enhanced the inhibitory effect of ADORA2A on YKL-40 synthesis, whereas its activation reversed the phenomenon. These results suggest that the activation of ADORA2A in astrocytes can inhibit the inflammation mediated by the STAT3/YKL-40 axis and thereby reduce white matter injury in cerebral small vessel disease.

Corrigendum: Adenosine A2A Receptor Suppressed Astrocyte-Mediated Inflammation through the Inhibition of STAT3/YKL-40 Axis in Mice with Chronic Cerebral Hypoperfusion-Induced White Matter Lesions.

[This corrects the article DOI: 10.3389/fimmu.2022.841290.].

Targeted Treatment of Ischemic Stroke by Bioactive Nanoparticle-Derived Reactive Oxygen Species Responsive and Inflammation-Resolving Nanotherapies.

Stroke is a primary cause of death and disability worldwide, while effective and safe drugs remain to be developed for its clinical treatment. Herein, we report bioactive nanoparticle-derived multifunctional nanotherapies for ischemic stroke, which are engineered from a pharmacologically active oligosaccharide material (termed as TPCD) prepared by covalently conjugating a radical-scavenging compound (Tempol) and a hydrogen-peroxide-eliminating moiety of phenylboronic acid pinacol ester (PBAP) on ß-cyclodextrin. Of note, combined functional moieties of Tempol and PBAP on ß-cyclodextrin contribute to antioxidative and anti-inflammatory activities of TPCD. Cellularly, TPCD nanoparticles (i.e., TPCD NPs) reduced oxygen-glucose deprivation-induced overproduction of oxidative mediators, increased antioxidant enzyme expression, and suppressed microglial-mediated inflammation, thereby inhibiting neuronal apoptosis. After intravenous (i.v.) delivery, TPCD NPs could efficiently accumulate at the cerebral ischemic injury site of mice with middle cerebral artery occlusion (MCAO), showing considerable distribution in cells relevant to the pathogenesis of stroke. Therapeutically, TPCD NPs significantly decreased infarct volume and accelerated recovery of neurological function in MCAO mice. Mechanistically, efficacy of TPCD NPs is achieved by its antioxidative, anti-inflammatory, and antiapoptotic effects. Furthermore, TPCD NPs can function as a reactive oxygen species labile nanovehicle to efficiently load and triggerably release an inflammation-resolving peptide Ac2-26, giving rise to an inflammation-resolving nanotherapy (i.e., ATPCD NP). Compared to TPCD NP, ATPCD NP demonstrated notably enhanced in vivo efficacies, largely resulting from its additional inflammation-resolving activity. Consequently, TPCD NP-derived nanomedicines can be further developed as promising targeted therapies for stroke and other inflammation-associated cerebrovascular diseases.

[Authentification of Radix Cyathule and its adulterants based on SCAR markers].

Chuanniuxi (Radix Cyathule) is one of the most important geo-herb in Sichuan province, which adulterants are Hongniuxi (Cyathula capitata) and Huainiuxi (Achyranthes bidentata). In this paper Chuanniuxi and its adulterants were identified by SCAR markers. Nineteen populations from Tianquan, Baoxin, Huili and Jinkouhe were collected and their RAPD fingerprints were established. Based on the RAPD patterns, two polymorphic bands F300 and F500 were selected, recycled, cloned and sequenced. According to the sequences two pairs of sequence characterized amplified regions (SCAR) primers were designed and used to amplify all materials to prove the efficiency of identification of the different populations. Chuanniuxi and Huiniuxi could be distinguished by the primer SC-320, Chuanniuxi and Hongniuxi could be distinguished by the primer SC-495. Combining the two SCAR markers, Chuanniuxi, Hongniuxi and huainiuxi could be identified effectively and quickly.