Z-scheme Al2SeTe/GaSe and Al2SeTe/InS van der Waals heterostructures for photocatalytic water splitting.

Designing Z-scheme van der Waals (vdW) heterostructured photocatalysts is a promising strategy for developing highly efficient overall water splitting. Herein, by employing density functional theory calculations, we systematically investigated the stability, electronic structures, photocatalytic and optical properties of Al2SeTe, GaSe, and InS monolayers and their corresponding vdW heterostructures. Interestingly, electronic structures show that all vdW heterostructures have direct band gaps, which is conducive to the transition of electrons from the valence band to the conduction band. Notably, Al2TeSe/GaSe and Al2TeSe/InS vdW heterostructures possess large overpotentials for Z-scheme photocatalytic water splitting, as proved by the results of band edge positions and band structure bending. Moreover, these vdW heterostructures exhibit good optical absorption in ultraviolet and visible light regions. We believe that our findings will open a new avenue for the modulation and development of Al2TeSe/GaSe and Al2TeSe/InS vdW heterostructures for photocatalytic water splitting.

A novel TRIM22 gene polymorphism promotes the response to PegIFNα therapy through cytokine-cytokine receptor interaction signaling pathway in chronic hepatitis B.

IMPORTANCE: Pegylated interferon alfa (PegIFNα) has limited efficacy in the treatment of chronic hepatitis B (CHB). Although many biomarkers related to hepatitis B virus (HBV) have been proposed to stratify patients, the response rate to PegIFNα is still unsatisfactory. Herein, our data suggest that the single-nucleotide polymorphism (SNP) rs10838543 in TRIM22 potentiates a positive clinical response to PegIFNα treatment in patients with hepatitis B e antigen-positive CHB by increasing the levels of IFNL1, CCL3, and CCL5. These observations can help guide treatment decisions for patients with CHB to improve the response rate to PegIFNα.

Dynamic monitoring of TGW6 by selective autophagy during grain development in rice.

Crop yield must increase to achieve food security in the face of a growing population and environmental deterioration. Grain size is a prime breeding target for improving grain yield and quality in crop. Here, we report that autophagy emerges as an important regulatory pathway contributing to grain size and quality in rice. Mutations of rice Autophagy-related 9b (OsATG9b) or OsATG13a causes smaller grains and increase of chalkiness, whereas overexpression of either promotes grain size and quality. We also demonstrate that THOUSAND-GRAIN WEIGHT 6 (TGW6), a superior allele that regulates grain size and quality in the rice variety Kasalath, interacts with OsATG8 via the canonical Atg8-interacting motif (AIM), and then is recruited to the autophagosome for selective degradation. In consistent, alteration of either OsATG9b or OsATG13a expression results in reciprocal modulation of TGW6 abundance during grain growth. Genetic analyses confirmed that knockout of TGW6 in either osatg9b or osatg13a mutants can partially rescue their grain size defects, indicating that TGW6 is one of the substrates for autophagy to regulate grain development. We therefore propose a potential framework for autophagy in contributing to grain size and quality in crops.

miR-548c-3p targets TRIM22 to attenuate the Peg-IFN-α therapeutic efficacy in HBeAg-positive patients with chronic hepatitis B.

Chronic hepatitis B (CHB) patients treated with interferon shows encouraging results. However, its clinical efficacy is limited by significant individual differences in treatment responses. We identified an interferon-inducible effector, TRIM22, as the likely causal target of such differential responses. We found that TRIM22 was highly expressed in interferon-responsive patients and negatively correlated with HBV DNA and HBeAg serum levels. Stable cells overexpressing TRIM22 carried significantly less HBsAg, HBeAg, and HBV DNA, and cells with knocked-down TRIM22 by shRNA displayed higher levels of these markers than controls. Integrated bioinformatics analysis and subsequent experiments revealed that TRIM22 overexpression significantly increased the supernatant levels of IL-1ß and IL-8, two important cytokines of NOD2/NF-κB pathway involved in interferon-induced antiviral activities. We identified three candidate microRNAs binding to 3'UTR of TRIM22 at various locations through typical imperfect paring using the TargetScan program. MiR-548c-3p appeared to be highly expressed, while the TRIM22 level was low in the suboptimal response group of CHB patients. The Luciferase reporter assay revealed an interaction between miR-548c-3p and the 3'UTR of TRIM22, leading to a controlled suppression of TRIM22 endogenous expression. This resulted in interferon's substantially weakened therapeutic efficacy, as indicated by the elevation of the serum levels of HBsAg, HBeAg and HBV DNA in miR-548c-3p-transfected HepAD38 cells. Our study demonstrated that a particular miR-548c-3p is the key negative regulator of TRIM22 in CHB patients with a weak response to interferon treatment, providing a novel marker and target in interferon-α therapy evaluation.

Metabolome and transcriptome analysis of terpene synthase genes and their putative role in floral aroma production in Litchi chinensis.

Volatile organic compounds (VOCs) are essential traits of flowers since they attract pollinators, aid in seed distribution, protect the plant from internal and external stimuli, and are involved in plant-plant and plant-environment interactions. Apart from their role in plants, VOCs are used in pharmaceuticals, fragrances, cosmetics, and flavorings. Litchi (Litchi chinensis Sonn.) is a popular fruit due to its enticing red appearance, exotic taste, and high nutritional qualities. Litchi flowers bloom as inflorescences primarily on the shoot terminals. There are three distinct flower types, two male and one female, all of which are produced on the same panicle and rely on insect pollination. Herein, we used a comprehensive metabolomic approach to examine the volatile profile of litchi fruit (green pericarp, yellow pericarp, and red pericarp) as well as male and female flowers (bud stage, half open and full bloom). From a quantitative examination of the volatiles in L. chinensis, a total of 19, 22, and 21 VOCs were discovered from female flowers, male flowers, and fruits, with the majority of them belonging to sesquiterpenes. Multivariate analysis revealed that the volatile profiles of fruits differ from those of male and female flowers. Three VOCs were unique to male flowers and ten to the fruit, while eight VOCs were shared by both male and female flowers and eleven by both male and female flowers and the fruit. Furthermore, for the first time, we identified and comprehensively studied the TERPENE SYNTHASE genes (TPS) using the litchi genome and transcriptome database, which revealed 38 TPS genes unevenly distributed across the 15 chromosomes. A phylogenetic study showed that LcTPS were grouped into TPS-b, TPS-c, TPS-e, TPS-f, and TPS-g subfamilies, with TPS-b having the most genes. The conserved motifs (RRX8 W, NSE/DTE, and DDXX D) were studied in LcTPSs, and significant variation between subfamilies was discovered. Furthermore, after integrating the metabolome and transcriptome datasets, several VOCs were shown to be development-specific and highly linked with distinct LcTPS genes, making them promising biomarkers. Interestingly, LcTPS17/20/23/24/31 were associated with monoterpene edges, while the rest were connected to sesquiterpene edges, indicating their probable participation in the aroma biosynthesis mechanism of certain compounds.

Hypocomplementemia in primary Sjogren's syndrome: association with serological, clinical features, and outcome.

OBJECTIVE: The aim of the present study was to assess the clinical characteristic of hypocomplementemia (HC) in primary Sjogren's syndrome (pSS), and to address possible risk factors and the prognosis associated with HC in pSS patients. METHODS: pSS patients with HC in Hebei General Hospital from September 2016 to March 2019 were retrospectively analyzed and compared to those with normocomplementemia (NC). Logistic regression analysis was used to detect risk factors. RESULTS: Of the 333 patients with pSS, 84 patients (25.23%) were presented with HC at diagnosis. The presence of hyper-IgG and anti-Ro52 antibodies was significantly more common in patients with HC. In addition to systemic involvement, pSS patients with HC had more hematological, renal, and nervous system involvement, and received more immunosuppressant treatments than NC group (p < 0.05). ESSDAI score was significantly higher in patients with HC (p < 0.05). Multivariate logistic analysis indicated that leukopenia (OR = 2.23) and hyper-IgG (OR = 2.13) were independent risk factors for pSS with HC. In addition, profound CD16/CD56+ NK-cell lymphopenia was found in pSS-HC patients. More pSS patients developed SLE in the HC group than NC group (4.76% vs. 0.80%, p = 0.04) during the follow-up. CONCLUSION: HC was not an uncommon manifestation of pSS and had an independent association with the main clinical and immunological features. Patients with pSS-HC had an increased possibility to develop SLE that required more positive treatment with glucocorticoids and immunosuppressants. KEY POINTS: • Hypocomplementemia had an independent association with the main clinical and immunological features in primary Sjogren's syndrome patients. • ESSDAI score was significantly higher in patients with hypocomplementemia. • The pSS patients with hypocomplementemia had an increased possibility to develop SLE.

Interstitial lung disease in Primary Sjögren's syndrome.

BACKGROUND: Interstitial lung disease (ILD) may cause life-threatening complications of primary Sjogren's syndrome (pSS), and has a poor prognosis in terms of survival and quality of life. To date, few studies have investigated the risk factors for ILD detected by high-resolution computed tomography (HRCT) in pSS patients with or without respiratory symptoms. METHODS: Data of 333 patients with newly diagnosed pSS were retrospectively analysed. Interstitial lung disease involvement was defined as typical abnormalities on HRCT and/or pulmonary function tests. Multivariate regression model was used to evaluate the association between interstitial lung disease and pSS characteristics. RESULTS: Sixty-six patients (19.82%) were diagnosed with pSS-ILD. Ground glass opacities (87.88%) and septal/sub pleural lines (81.82%) were most frequent. Based on pulmonary high-resolution computed tomography, patients were divided into nonspecific (n = 42), usual (n = 20), lymphocytic interstitial pneumonia (n = 3) and cryptogenic organising pneumonia (n = 1) groups. There was a strong association between erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP) and the HRCT-score. Pulmonary function tests revealed impaired diffusion capacity for carbon monoxide and total lung capacity, and coexistence of small airway lesions in pSS-interstitial lung disease. On logistic regression analysis, age, Raynaud's phenomenon, lymphopenia, cough, dyspnoea and rampant dental caries were risk factors associated with pSS-interstitial lung disease. CONCLUSIONS: Interstitial lung disease involvement in pSS is a common clinical occurrence. The clinical manifestation is nonspecific and variable; Raynaud's phenomenon and lymphopenia may predict its onset. pSS patients with advanced age, dry cough and dyspnoea should be systematically evaluated for ILD involvement and managed according to their symptoms.

ATG8-Interacting Motif: Evolution and Function in Selective Autophagy of Targeting Biological Processes.

Autophagy is an evolutionarily conserved vacuolar process functioning in the degradation of cellular components for reuse. In plants, autophagy is generally activated upon stress and its regulation is executed by numbers of AuTophaGy-related genes (ATGs), of which the ATG8 plays a dual role in both biogenesis of autophagosomes and recruitment of ATG8-interacting motif (AIM) anchored selective autophagy receptors (SARs). Such motif is either termed as AIM or ubiquitin-interacting motif (UIM), corresponding to the LC3-interacting region (LIR)/AIM docking site (LDS) or the UIM docking site (UDS) of ATG8, respectively. To date, dozens of AIM or UIM containing SARs have been characterized. However, the knowledge of these motifs is still obscured. In this review, we intend to summarize the current understanding of SAR proteins and discuss the conservation and diversification of the AIMs/UIMs, expectantly providing new insights into the evolution of them in various biological processes in plants.

Harmony but Not Uniformity: Role of Strigolactone in Plants.

Strigolactones (SLs) represent an important new plant hormone class marked by their multifunctional roles in plants and rhizosphere interactions, which stimulate hyphal branching in arbuscular mycorrhizal fungi (AMF) and seed germination of root parasitic plants. SLs have been broadly implicated in regulating root growth, shoot architecture, leaf senescence, nodulation, and legume-symbionts interaction, as well as a response to various external stimuli, such as abiotic and biotic stresses. These functional properties of SLs enable the genetic engineering of crop plants to improve crop yield and productivity. In this review, the conservation and divergence of SL pathways and its biological processes in multiple plant species have been extensively discussed with a particular emphasis on its interactions with other different phytohormones. These interactions may shed further light on the regulatory networks underlying plant growth, development, and stress responses, ultimately providing certain strategies for promoting crop yield and productivity with the challenges of global climate and environmental changes.

Conserved and Diversified Mechanism of Autophagy between Plants and Animals upon Various Stresses.

Autophagy is a highly conserved degradation mechanism in eukaryotes, executing the breakdown of unwanted cell components and subsequent recycling of cellular material for stress relief through vacuole-dependence in plants and yeast while it is lysosome-dependent in animal manner. Upon stress, different types of autophagy are stimulated to operate certain biological processes by employing specific selective autophagy receptors (SARs), which hijack the cargo proteins or organelles to the autophagy machinery for subsequent destruction in the vacuole/lysosome. Despite recent advances in autophagy, the conserved and diversified mechanism of autophagy in response to various stresses between plants and animals still remain a mystery. In this review, we intend to summarize and discuss the characterization of the SARs and their corresponding processes, expectantly advancing the scope and perspective of the evolutionary fate of autophagy between plants and animals.

Computational Study of Novel Semiconducting Sc2CT2 (T = F, Cl, Br) MXenes for Visible-Light Photocatalytic Water Splitting.

Seeking candidate photocatalysts for photocatalytic water splitting, via visible light, is of great interest and importance. In this study, we have comprehensively explored the crystal structures, electronic properties, and optical absorbance of two-dimensional (2D) Sc2CT2 (T = F, Cl, Br) MXenes and their corresponding photocatalytic water splitting, under the visible-light region, by first-principles calculations. Herein, we have proposed that 2D Sc2CT2 MXenes can be fabricated from their layered bulk compounds, alternatively to the traditional chemical etching method. Creatively, we proposed Sc2CT2 (T = F, Br) as new materials; the band edge alignments of Sc2CF2 can be tuned to meet the water redox potentials at pH = 8.0. It is highlighted that Sc2CF2 shows outstanding optical spectra harvested under visible-light wavelength regions, and efficient separation of photo-induced electrons and holes in different zones. These present results provide eloquent evidence and open a new door on the photocatalysis applications of such novel semiconducting MXenes.

Tai Chi exercise improves age-associated decline in cerebrovascular function: a cross-sectional study.

BACKGROUND: Tai Chi exercise has been reported to enhance physical and mental health in the older adults; however, the mechanism remains elusive. TRIAL DESIGN: We recruited 289 older adults practicing Tai Chi for over 3 years, together with 277 age-matched older and 102 young adults as controls. 168 Tai Chi practitioners were successfully matched to 168 older controls aged 60-69 based on a propensity score for statistics. METHODS: Cerebrovascular function was evaluated by measuring the hemodynamics of the carotid artery. Spearman correlation was performed to validate the age-associated physiological parameters. RESULTS: Cerebrovascular function in older adults significantly degenerated compared with the young, and was substantially correlated with age. Compared with the older control group, Tai Chi practitioners showed significant improvements in CVHI (cerebral vascular hemodynamics indices) Score (P = 0.002), mean blood flow velocity (P = 0.014), maximal blood flow velocity (P = 0.04) and minimum blood flow velocity (P < 0.001), whereas the age-related increases in pulse wave velocity (P = 0.022), characteristic impedance (P = 0.021) and peripheral resistance (P = 0.044) were lowered. CONCLUSIONS: These data demonstrate a rejuvenation role of Tai Chi in improving the age-related decline of the cerebrovascular function. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR1900025187).

Bigu-Style Fasting Affects Metabolic Health by Modulating Taurine, Glucose, and Cholesterol Homeostasis in Healthy Young Adults.

BACKGROUND: Dynamic orchestration of metabolic pathways during continuous fasting remains unclear. OBJECTIVE: We investigated the physiological effects of Bigu-style fasting and underlying metabolic reprogramming in healthy adults. METHODS: We conducted a 5-d Bigu trial in 43 healthy subjects [age 23.2 ± 2.4 y; BMI (in kg/m2) 22.52 ± 1.79]. Physiological indicators and body composition were monitored daily during fasting day 1 (F1D) to F5D and after 10-d refeeding postfasting (R10D) and R30D. Blood samples were collected in the morning. Risk factors associated with inflammation, aging, cardiovascular diseases, malnutrition, and organ dysfunction were evaluated by biochemical measurements. Untargeted plasma metabolomics and gut microbial profiling were performed using plasma and fecal samples. Data were analyzed by repeated measures ANOVA with Greenhouse-Geisser correction. Correlation analyses for metabolite modules and taurine were analyzed by Spearman's rank and Pearson tests, respectively. RESULTS: Heart rate was accelerated throughout the fasting period. Risk factors associated with inflammation and cardiovascular diseases were significantly lowered during or after Bigu (P < 0.05). Body composition measurement detected an overconsumption of fat starting from F3D till 1 mo after refeeding. Metabolomics unveiled a coupling between gluconeogenesis and cholesterol biosynthesis beyond F3D. Plasma taurine significantly increased at F3D by 31%-46% followed by a reduction to basal level at F5D (P < 0.001), a pattern inversely correlated with changes in glucose and de novo synthesized cholesterol (r = -0.407 and -0.296, respectively; P < 0.001). Gut microbial profiling showed an enrichment of taurine-utilizing bacteria at F5D, which was completely recovered at R10D. CONCLUSIONS: Our data demonstrate that 5-d Bigu is potentially beneficial to health in young adults. A starvation threshold of 3-d fasting is necessary for maintaining glucose and cholesterol homeostasis via a taurine-microbiota regulatory loop. Our findings provide novel insights into the physiological and metabolic responses of the human body to continuous Bigu-style fasting. This trial was registered at http://www.chictr.org.cn as ChiCTR1900022917.

Clinical features and risk factors of Raynaud's phenomenon in primary Sjögren's syndrome.

OBJECTIVE: The aim at the current study was to investigate the clinical characteristics and risk factors of Raynaud's phenomenon (RP) in patients with primary Sjögren's syndrome (pSS). METHODS: Retrospective analysis of the medical records of 333 new-onset pSS patients was performed. Demographic, clinical, and serological data were compared between individuals with and without RP. Logistic regression analysis was used to identify risk factors. RESULTS: RP was present in 11.41% of the pSS patients. pSS-RP patients were younger (49.74±14.56 years vs. 54.46±13.20 years, p=0.04) and exhibited higher disease activity (11 [5.75-15] vs. 7 [4-12], p=0.03) than those without. The prevalence of lung involvement was significantly higher in pSS patients with RP (60.53% vs. 17.29%; p<0.001). A significantly higher proportion of patients with pSS-RP tested positive about antinuclear (ANA), anti-RNP, and anti-centromere antibodies (ACA) compared to those without (p=0.003, <0.001, and 0.01, respectively). Multivariate analysis identified lung involvement (odds ratio [OR]=8.81, 95% confidence interval [CI] 2.02-38.47; p=0.04), anti-RNP positive status (OR=79.41, 95% CI 12.57-501.78; p<0.0001), as well as ACA (OR=13.17, 95% CI 2.60-66.72; p=0.002) as prognostic factors for pSS-RP. CONCLUSION: The presence of RP defined a subset of pSS with a unique phenotype, manifesting as increased lung involvement and a higher frequency of anti-RNP antibodies and ACA, as well as greater disease activity. These results suggest that RP has clinical and prognostic value of pSS patients. Further prospective studies with a larger number of subjects are warranted to confirm our findings and assess the prognostic and treatment implications of RP in pSS patients. Key Points • Raynaud's phenomenon (RP) was present in 38 (11.41%) of 333 patients with primary Sjögren's syndrome (pSS), with patients with RP exhibiting a younger age and higher disease activity. • The presence of RP indicates a subset of pSS with a unique phenotype, with manifestations including increased lung involvement and a higher frequency of anti-RNP antibodies and anti-centromere antibodies. • Patients with pSS and RP need close follow-up and long-term observation (including assessment of microangiopathy), with specific attention paid to the possible development of clinical features of systemic sclerosis.

Autophagy Dances with Phytohormones upon Multiple Stresses.

Autophagy is an evolutionarily conserved process for turning over unwanted cellular components, thus promoting nutrient recycling and maintaining cellular homeostasis, which eventually enables plants to survive unfavorable growth conditions. In addition to plant growth and development, previous studies have demonstrated that autophagy is involved in the responses to various environmental challenges through interplaying with multiple phytohormones, including abscisic acid (ABA), jasmonic acid (JA), and salicylic acid (SA). In this review, we summarize the advances made in their synergistic interactions in response to multiple abiotic and biotic stresses; we also discuss the remaining issues and perspectives regarding their crosstalk.

Synergistic Interaction of Phytohormones in Determining Leaf Angle in Crops.

Leaf angle (LA), defined as the angle between the plant stem and leaf adaxial side of the blade, generally shapes the plant architecture into a loosen or dense structure, and thus influences the light interception and competition between neighboring plants in natural settings, ultimately contributing to the crop yield and productivity. It has been elucidated that brassinosteroid (BR) plays a dominant role in determining LA, and other phytohormones also positively or negatively participate in regulating LA. Accumulating evidences have revealed that these phytohormones interact with each other in modulating various biological processes. However, the comprehensive discussion of how the phytohormones and their interaction involved in shaping LA is relatively lack. Here, we intend to summarize the advances in the LA regulation mediated by the phytohormones and their crosstalk in different plant species, mainly in rice and maize, hopefully providing further insights into the genetic manipulation of LA trait in crop breeding and improvement in regarding to overcoming the challenge from the continuous demands for food under limited arable land area.

Autophagy in Plant: A New Orchestrator in the Regulation of the Phytohormones Homeostasis.

Autophagy is a highly evolutionarily-conserved catabolic process facilitating the development and survival of organisms which have undergone favorable and/or stressful conditions, in particular the plant. Accumulating evidence has implicated that autophagy is involved in growth and development, as well as responses to various stresses in plant. Similarly, phytohormones also play a pivotal role in the response to various stresses in addition to the plant growth and development. However, the relationship between autophagy and phytohormones still remains poorly understood. Here, we review advances in the crosstalk between them upon various environmental stimuli. We also discuss how autophagy coordinates the phytohormones to regulate plant growth and development. We propose that unraveling the regulatory role(s) of autophagy in modulating the homeostasis of phytohormones would benefit crop breeding and improvement under variable environments, in particular under suboptimal conditions.

Constitutive expression of REL1 confers the rice response to drought stress and abscisic acid.

Leaf rolling is one of the most significant symptoms of drought stress in plant. Previously, we identified a dominant negative mutant, termed rolled and erect 1 (hereafter referred to rel1-D), regulating leaf rolling and erectness in rice. However, the role of REL1 in drought response is still poorly understood. Here, our results indicated that rel1-D displayed higher tolerance to drought relative to wild type, and the activity of superoxide dismutase (SOD) and drought responsive genes were significantly up-regulated in rel1-D. Moreover, our results revealed that rel1-D was hypersensitive to ABA and the expression of ABA associated genes was significantly increased in rel1-D, suggesting that REL1 likely coordinates ABA to regulate drought response. Using the RNA-seq approach, we identified a large group of differentially expressed genes that regulate stimuli and stresses response. Consistently, we also found that constitutive expression of REL1 alters the expression of biotic and abiotic stress responsive genes by the isobaric tags for relative and absolute quantification (iTRAQ) analysis. Integrative analysis demonstrated that 8 genes/proteins identified by both RNA-seq and iTRAQ would be the potential targets in term of the REL1-mediated leaf morphology. Together, we proposed that leaf rolling and drought tolerance of rel1-D under normal condition might be caused by the endogenously perturbed homeostasis derived from continuous stressful dynamics.

Baicalin's Therapeutic Time Window of Neuroprotection during Transient Focal Cerebral Ischemia and Its Antioxidative Effects In Vitro and In Vivo.

We investigated the effects of baicalin on an ischemia-reperfusion-induced brain injury model in rats and its antioxidative activities in vitro and in vivo. An ischemia-reperfusion injury of the brain via a middle cerebral artery occlusion (MCAO) was induced in rats. Baicalin was injected at different time points (0, 2, 4, and 6 h) after the MCAO was induced. Baicalin can improve neurological function and significantly decrease brain infarction within a time window of 4 h. Moreover, baicalin was able to reduce cell apoptosis and had the strong antioxidative effect of reducing reactive oxygen species production and malondialdehyde generation. In contrast, baicalin interfered with superoxide dismutase and nicotinamide adenine dinucleotide 2'-phosphate oxidase activities. Moreover, baicalin also exhibited strong neuroprotective effects against H2O2-mediated injury and improved the SOD activity of neurons. Furthermore, baicalin demonstrated good scavenging of hydroxyl radicals, superoxide anions, and DPPH radicals and exerted an additional effect of inhibiting xanthine oxidase. Baicalin showed beneficial effects against MCAO-induced injury within a 4 h time window, and its antioxidative effects both in vitro and in vivo may partly elucidate its mechanism of action.

Refined Qingkailing Protects MCAO Mice from Endoplasmic Reticulum Stress-Induced Apoptosis with a Broad Time Window.

In the current study, we are investigating effect of refined QKL on ischemia-reperfusion-induced brain injury in mice. Methods. Mice were employed to induce ischemia-reperfusion injury of brain by middle cerebral artery occlusion (MCAO). RQKL solution was administered with different doses (0, 1.5, 3, and 6 mL/kg body weight) at the same time of onset of ischemia, and with the dose of 1.5 mL/kg at different time points (0, 1.5, 3, 6, and 9 h after MCAO). Neurological function and brain infarction were examined and cell apoptosis and ROS at prefrontal cortex were evaluated 24 h after MCAO, and western blot and intracellular calcium were also researched, respectively. Results. RQKL of all doses can improve neurological function and decrease brain infarction, and it performed significant effect in 0, 1.5, 3, and 6 h groups. Moreover, RQKL was able to reduce apoptotic process by reduction of caspase-3 expression, or restraint of eIF2a phosphorylation and caspase-12 activation. It was also able to reduce ROS and modulate intracellular calcium in the brain. Conclusion. RQKL can prevent ischemic-induced brain injury with a time window of 6 h, and its mechanism might be related to suppress ER stress-mediated apoptotic signaling.