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Growth-regulating factors (GRFs) are plant-specific transcription factors that contain two highly conserved QLQ and WRC domains, which control a range of biological functions, including leaf growth, floral organ development, and phytohormone signaling. However, knowledge of the evolutionary patterns and driving forces of GRFs in Gramineae crops is limited and poorly characterized. In this study, a total of 96 GRFs were identified from eight crops of Brachypodium distachyon, Hordeum vulgare, Oryza sativa L. ssp. indica, Oryza rufipogon, Oryza sativa L. ssp. japonica, Setaria italic, Sorghum bicolor and Zea mays. Based on their protein sequences, the GRFs were classified into three groups. Evolutionary analysis indicated that the whole-genome or segmental duplication plays an essential role in the GRFs expansion, and the GRFs were negatively selected during the evolution of Gramineae crops. The GRFs protein function as transcriptional activators with distinctive structural motifs in different groups. In addition, the expression of GRFs was induced under multiple hormonal stress, including IAA, BR, GA3, 6BA, ABA, and MeJ treatments. Specifically, OjGRF11 was significantly induced by IAA at 6 h after phytohormone treatment. Transgenic experiments showed that roots overexpressing OjGRF11 were more sensitive to IAA and affect root elongation. This study will broaden our insights into the origin and evolution of the GRF family in Gramineae crops and will facilitate further research on GRF function.

ObjectiveTo compare the efficacy of Percutaneous mechanical thrombectomy (PMT) and Catheter directed thrombolysis (CDT) in the treatment of patients with moderate and high-risk ape and explore the clinical application value of biomarkers in the treatment of moderate and high-risk ape.MethodA total of 84 patients with ape were selected from the Department of vascular surgery of the Second Affiliated Hospital of Shandong First Medical University and the Department of vascular surgery of Shanghai Ninth People's Hospital Affiliated with Shanghai Jiao Tong University School of Medicine. According to the relevant guidelines, they were divided into high-risk and medium-risk groups, including PMT groups (35 cases) and CDT groups (49 cases). To detect the changes of serum B-type brain natriuretic peptide (BNP),Troponin I (TnI) and plasma D-dimer/fibrinogen ratio (DFR) levels in different risk stratification before and after PMT and CDT, the correlation and diagnostic value of each index, and compare the thrombus clearance rate, pulmonary artery pressure, average dosage of urokinase, effective thrombolytic time, average hospitalization time and complications of PMT and CDT.ResultUnder different treatment methods and risk stratification, there was no statistically significant difference in the clinical data of patients at general baseline;The preoperative BNP, TnI and DFR levels of PMT and CDT in the middle and high risk stratification were significantly lower than those in the other groups (P P P ConclusionSerum BNP, TnI and plasma DFR levels can reflect the risk stratification and better clinical diagnostic value of ape,PMT and CDT are used to treat high-risk ape. For hospitals with medical conditions, PMT is more worthy of clinical recommendation.

Background: Combination of Polygonum capitatum Buch.-Ham. ex D. Don extract (PCE) and ciprofloxacin (CIP) was commonly prescribed in the treatment of urinary tract infections. Their pharmacokinetic herb-drug interactions (HDIs) were focused in this study to assess potential impact on the safety and effectiveness.Methods: A randomized, three-period, crossover trial was designed to study the pharmacokinetic HDI between PCE and CIP in healthy humans. Their pharmacokinetic- and tissue distribution-based HDIs were also evaluated in rats. Gallic acid (GA) and protocatechuic acid (PCA) were chosen as PK-markers of PCE in humans and rats. Potential drug interaction mechanisms were revealed by assessing the effects of PCE on the activity and expression of multiple transporters, including OAT1/3, OCT2, MDR1, and BCRP.Results: Concurrent use of PCE substantially reduced circulating CIP (approximately 40%–50%) in humans and rats, while CIP hardly changed circulating GA and PCA. PCE significantly increased the tissue distribution of CIP in the prostate and testis of rats, but decreased in liver and lungs. Meanwhile, CIP significantly increased the tissue distribution of GA or PCA in the prostate and testis of rats, but decreased in kidney and heart. In the transporter-mediated in vitro HDI, GA and PCA presented inhibitory effects on OAT1/3 and inductive effects on MDR1 and BCRP.Conclusion: Multiple transporter-mediated HDI contributes to effects of PCE on the reduced systemic exposure and altered tissue distribution of CIP. More attention should be paid on the potential for PCE-perpetrated interactions.

ObjectiveIn this study, we aimed to explore the alterations in gut microbiota composition and cytokine responses related to disease progression, severity, and outcomes in patients with hypertensive intracerebral hemorrhage (ICH).MethodsFecal microbiota communities of 64 patients with ICH, 46 coronary heart disease controls, and 23 healthy controls were measured by sequencing the V3-V4 region of the 16S ribosomal RNA (16S rRNA) gene. Serum concentrations of a broad spectrum of cytokines were examined by liquid chips and ELISA. Relationships between clinical phenotypes, microbiotas, and cytokine responses were analyzed in the group with ICH and stroke-associated pneumonia (SAP), the major complication of ICH.ResultsIn comparison with the control groups, the gut microbiota of the patients with ICH had increased microbial richness and diversity, an expanded spectrum of facultative anaerobes and opportunistic pathogens, and depletion of anaerobes. Enterococcus enrichment and Prevotella depletion were more significant in the ICH group and were associated with the severity and functional outcome of ICH. Furthermore, Enterococcus enrichment and Prevotella depletion were also noted in the SAP group in contrast to the non-SAP group. Enterococci were also promising factors in the prognosis of ICH. The onset of ICH induced massive, rapid activation of the peripheral immune system. There were 12 cytokines (Eotaxin, GM-CSF, IL-8, IL-9, IL-10, IL-12p70, IL-15, IL-23, IL-1RA, IP-10, RANTES, and TNF-α) changed significantly with prolongation of ICH, and the Th2 responses correlated with the 90-day outcomes. Cytokines TNF-α, IP-10, IL-1RA, IL-8, IL-18, and MIP-1β in SAP group significantly differed from non-SAP group. Among these cytokines, only IP-10 levels decreased in the SAP group. Enterococcus was positively associated with IL-1RA and negatively associated with IP-10, while Prevotella was inversely associated in both the ICH and SAP groups.ConclusionThis study revealed that gut dysbiosis with enriched Enterococcus and depleted Prevotella increased the risk of ICH and subsequently SAP. The altered gut microbiota composition and serum cytokine profiles are potential biomarkers that reflect the inciting physiologic insult/stress involved with ICH.

BackgroundTo evaluate the outcomes of percutaneous mechanical thrombectomy (PMT) with Rotarex catheter in patients with acute lower limb ischemia (ALI) caused by aorto-iliac occlusion.Materials and MethodsData of patients with ALI caused by aorto-iliac occlusion in our institutions from January 2010 and April 2020 were reviewed. The primary end point was limb salvage rate. The secondary end points included technical success rate, survival rate, complications after the operation and during the follow-up.ResultsA total of 85 patients with ALI was diagnosed with aorto-iliac occlusion. Thirty-eight patients were treated by PMT with Rotarex catheter and enrolled in present study. Twenty-four were male (63.2%), and 14 were female (36.8%). The mean age was 66 years (range 28–83). All 38 patients were treated with PMT, with additional catheter directed thrombolysis (2/38, 5.3%), balloon angioplasty (8/38, 21.1%) and stent deployment (7/38, 18.4%). The mean procedure time was 123 ± 31 min. Seven patients (18.4%) underwent continuous renal replacement therapy. Two patients received major amputations (above the knee) and 2 patients died for renal insufficiency and heart failure during the hospital stay. Thirty-day survival rate was 94.7% and limb salvage was 94.4%. The mean follow-up time was 14.0 months (8–22 months). There was no major amputation and target artery occlusion occurred during the follow-up period.ConclusionPMT with Rotarex catheter could be new option for acute aorto-iliac occlusion, leading to safe and effective results.

CuS nanoparticles (NPs) as an effective near-infrared absorption agent have been widely applied in the photothermal therapy (PTT) of cancer. However, little is known about the application of CuS NP-based PTT in alleviating arterial inflammation and restenosis, which affects the long-term prognosis of endovascular treatment. In this study, CuS NPs were synthesized and used as PTT nanoplatform for ameliorating arterial inflammation induced by mechanical injury of endovascular treatment. The macrophages possess powerful phagocytosis toward CuS NPs is evidenced by intracellular transmission electron microscopic imaging. As illustrated from Cell Counting Kit-8 assay and calcein AM/PI staining, an efficient depletion of macrophages by CuS NPs coculture combined with the irradiation with a 915-nm near-infrared laser was achieved. The endarterium injury/inflammation model was established by insertion of a 29G needle (BD Insulin Syringe Ultra-Fine®) to the left common carotid artery of an apolipoprotein E knockout mouse to mimic endarterium damage after endovascular treatment. Local injection of CuS NPs around the left common carotid artery followed by irradiation with a 915-nm INR laser significantly depleted infiltrated macrophages and alleviated arterial stenosis. This work emphasizes the role of CuS NPs as a PTT agent in post-injury remodeling of the arterial wall and provides an attractive target macrophage that can be depleted to alleviate arterial restenosis.

Trichophyton rubrum is a common dermatophyte of the skin. The aim of this experiment was to explore the role of nitric oxide (NO) in the inhibition of T. rubrum growth induced by 420-nm intense pulsed light (IPL). This study found that nitric oxide synthase (NOS) and NO levels were increased, whereas asymmetric dimethylarginine (ADMA) level, keratinase activity, and fungal viability were decreased after IPL treatment compared with the control condition in vitro. Moreover, micromorphology was damaged by IPL treatment. Fungal viability was increased, and the damage to the fungal structure was reduced after pretreatment with an NOS inhibitor (L-NMMA) compared with IPL treatment alone. Compared with IPL alone, pretreatment with L-NMMA decreased NOS expression and NO level and increased keratinase activity. We found that 420-nm IPL treatment can inhibit the growth of T. rubrum by regulating NO in vitro.

Objectives: To evaluate the effect of intense pulsed light (IPL) on Trichophyton rubrum and investigate its mechanism of action.Methods: The viability of fungi treated with IPL alone and with IPL combined with an NADPH oxidase inhibitor (DPI) pretreatment was determined by MTT assays. The reactive oxygen species (ROS) were quantified with a DCFH-DA fluorescent probe. Malondialdehyde (MDA) content and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were determined by commercial kits. The transcription of the Nox gene was quantified using quantitative real-time PCR (qRT-PCR) analysis, and micromorphology was observed using scanning electron microscopy (SEM). In addition, fungal keratinase activity was detected by measuring dye release from keratin azure.Results: The growth declined with statistical significance after 6 h of treatment (P < 0.001). The ROS and MDA content increased after IPL treatment, whereas the SOD and GSH-Px activity decreased. Nox gene expression was upregulated, and the micromorphology was damaged. Keratinase activity decreased. Fungi that received DPI pretreatment exhibited contrasting outcomes.Conclusion: We found that 420-nm IPL significantly inhibited the growth and pathogenicity of T. rubrum in vitro. A suggested mechanism involves Nox as a factor that mediates 420-nm IPL-induced oxidative damage of T. rubrum.

Warfarin is used as anticoagulant and Compound Danshen prescription (CDP) is able to promote blood circulation. The combination might produce a synergic effect for patients of coronary heart diseases (CHDs) with atrial fibrillation (AF). Whether the combination increases the bleeding risk of warfarin is unclear, so the effects of Compound Danshen dripping pill (CDDP) on the pharmacokinetics (PK) and pharmacodynamics (PD) profiles of warfarin was investigated in patients. The dose and blood concentrations of warfarin, the four indicators of blood coagulation, prothrombin time, activated partial thromboplatin time, thrombin time, fibrinogen, and international normalized ratio value were compared when with and without CDDP treatment. The population PK (PPK) and PPK-PD models were established to assess patient demographics, genetic polymorphisms and CDDP as covariates. And the Seattle Angina Questionnaire was used to evaluate clinical efficacy, and the bleeding risk of combination was analyzed. The results indicated that CDDP had little influence on PK and PD profiles of warfarin in most patients and the combination of CCDP and warfarin would be a promising alternative regime for CHD with AF patients. The study was registered on China Clinical Trial Registry with number ChiCTR-ONRC-13003523.