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Abstract Methotrexate is a widely used drug in clinical practice for the treatment of collagen vascular diseases and malignant tumors. It has good anti-inflammatory and anti-proliferative effects, but the cytotoxicity of methotrexate can cause various adverse reactions in patients. Studies have shown that the sensitivity and tolerance of different individuals to methotrexate is different. There are many reasons for this difference. Among them, genetic polymorphism is one of the main factors that cause individual differences. This article provides an overview of the genetic polymorphisms of key proteins involved in methotrexate metabolism and transport, such as MTHFR, FPGS, γ-GGH, ABC transporter, OATPs, SLC, TS and DHFR, are related to their efficacy and adverse reactions. The aim is to clarify the impact of genetic polymorphisms on the efficacy and adverse effects of methotrexate at the pharmacogenomic level, in order to provide a basis for the clinical application of methotrexate.

IntroductionThe potato (Solanum tuberosum L.), one of the most vital food crops worldwide, is sensitive to salinity. Brassinosteroids (BRs) are crucial in tolerance to various abiotic stresses. The constitutive photomorphogenesis and dwarf (CPD) gene encodes C-3 oxidase, which is a rate-limiting enzyme that controls the synthesis of BRs.MethodsIn this study, we used StCPD gene overexpression (T) and un-transgenic (NT) plants obtained from our former research to illustrate adaptive resistance to salt stress at levels of phenotype; cell ultrastructure, physiology, and biochemistry; hormone; and transcription.ResultsResults showed the accumulation of 2,4-epibrassionolide (EBL) in T potatoes. We found that under high salt situations, the changed Na+/K+ transporter gene expression was linked with the prevalent ionic responses in T plants, which led to lower concentrations of K+ and higher concentrations of Na+ in leaves. Furthermore, RNA-sequencing (RNA-seq) data elucidated that gene expressions in NT and T plants were significantly changed with 200-mM NaCl treatment for 24 h and 48 h, compared with the 0-h treatment. Functional enrichment analysis suggested that most of the differentially expressed genes (DEGs) were related to the regulation of BR-related gene expression, pigment metabolism process, light and action, and plant hormone signal transduction.DiscussionThese findings suggested that StCPD gene overexpression can alleviate the damage caused by salt stress and enhance the salt resistance of potato plantlets. Our study provides an essential reference for further research on BR regulation of plant molecular mechanisms in potatoes with stress tolerance.

Peanut pod shape is a heritable trait which affects the market acceptance of in-shell peanut products. In order to determine the genetic control of pod shape, six component traits of pod shape (pod length, pod width, pod length/width ratio, pod roundness, beak degree and constriction degree) were measured using an image-based phenotyping method. A recombinant inbred line (RIL) population consisting of 181 lines was phenotyped across three environments. Continuous distributions and transgressive segregations were demonstrated in all measured traits and environments. Significant correlations were found among most component traits with broad-sense heritability ranging from 0.87 to 0.95. Quantitative trait locus (QTL) analysis yielded 26 additive QTLs explaining 3.79 to 52.37% phenotypic variations. A novel, stable and major QTL region conditioning multiple shape features was detected on chromosome 2, which spans a 10.81-Mb genomic region with 543 putative genes. Bioinformatics analysis revealed several candidate genes in this region. In addition, 73 pairs of epistatic interactions involving 92 loci were identified for six component traits explaining 0.94–6.45% phenotypic variations. These results provide new genetic loci to facilitate genomics-assisted breeding of peanut pod shape.

Plants are vulnerable to many abiotic stresses, resulting in reduced plant productivity. Its adaptation to unfavorable environments relies on transmitting external stress signals into internal signaling pathways. A series of stress response mechanisms have been developed. Among them, brassinosteroids (BRs) are a class of steroid hormones that are widely involved in plant growth, development, and stress response. Via genetics, proteomics, and genomics studies, the major components of signaling and signaling pathways through a series of phosphorylation cascade reactions have been identified in model plants such as Arabidopsis. Numerous studies have shown that BRs play important roles in plant responses to drought, temperature, salt, heavy metals, and other environmental stresses. The application of BRs to improve plant stress resistance has become the focus of research in recent years, especially the regulation of stress via endogenous BRs. Therefore, this paper systematically summarizes the research progress related to endogenous BR levels and provides an overview of BR biosynthesis and the signaling pathway, as well as the function of endogenous BRs in the response to abiotic stresses.

Abstract Background As the nonalcoholic fatty liver disease (NAFLD) epidemic matures, understanding how metabolic changes in NAFLD development vary over the age distribution is important to guide precise prevention. We aimed to clarify metabolic trends in age-specific NAFLD incidence. Methods We conducted a 4-year longitudinal retrospective cohort study enrolling 10,240 consecutive healthy individuals who received annual physical examination during 2012–2019. Baseline and dynamic changes in metabolism and hepatic steatosis determined with ultrasound were collected and analyzed stratified by age into the following groups: 20–34, 35–49, 50–64, and over 65 years. Results Overall, 1701 incident NAFLD participants (16.6%) were identified. Adjusted Cox regression analysis showed that the baseline and increased body mass index were the main risk factors for NAFLD in people ≤ 65 years old. Baseline high-density lipoprotein (HR = 0.56; 95% CI 0.39–0.78) was a protective factor for newly onset NAFLD in the 50-to-64-year-old group, while baseline SBP (HR = 1.03; 95% CI 1.01–1.05), baseline uric acid (HR = 1.04; 95% CI 1.01–1.07), triglyceride increase (HR = 4.76; 95% CI 3.69–6.14), fasting blood glucose increase (HR = 1.32; 95% CI 1.06–1.65) were independently associated with incident NAFLD in over-65-year-old group. Conclusions NAFLD incidence attributable to potentially metabolic risk factors varied substantially across age groups in a cohort of Chinese people. The adoption of age targeted metabolic prevention strategies might reduce the burden of NAFLD.

Abstract Foodborne Listeria monocytogenes poses serious threats to public health. Fast and sensitive detection of the pathogen at the point of contamination is thus crucial to halt the spread of bacteria‐related diseases. Herein, we report for the first time a fluorescent film sensor to detect the biomarker of L. monocytogenes, 3‐hydroxy‐2‐butanone. The sensor demonstrated unprecedented sensing performance for the analyte with a detection limit lower than 0.05 mg/m3, response time less than 1 s, full reversibility, and excellent selectivity. Further study showed that the sensor can be used to monitor the growth of L. monocytogenes with much‐improved sensitivity. The superior performance of the sensor is ascribed to the specific binding, efficient charge transfer emission, and porous adlayer structure of the specially designed sensing fluorophore‐based film. Our work paves the way to develop a portable detector to meet the needs for on‐site and real‐time detection of foodborne pathogens.

BackgroundFor patients with symptomatic intracranial and vertebral artery stenosis who receive endovascular treatment, in-stent restenosis (ISR) is associated with the recurrence of ischemic stroke. This study evaluated a drug-eluting stent (DES) vs. bare metal stent (BMS) for the treatment of symptomatic intracranial and vertebral artery stenosis.MethodsThe trial was a multicenter, 1:1 randomized, prospective feasibility clinical trial with 10 participating centers in China from March 2014 to October 2015. Eligible patients had symptomatic intracranial and vertebral artery stenosis (70%−99%) and had medical drug treatment failure. The primary endpoint was the rate of in-stent restenosis at 180 days of randomization. The secondary endpoint was a composite of the following two outcomes: (1) ischemic stroke or transient cerebral ischemia (TIA) in the same territory as the presenting event (distal to the target lesion) between 30 days and 1 year after randomization and (2) successful stent implantation. The safety outcome was the presence of stroke in any territory and death within 30 days of randomization or adverse events. Group t-tests or Wilcoxon rank-sum tests were used for the intergroup comparison of quantitative data according to the data distribution. The chi-square test or exact probability method was used for the classification data. The Wilcoxon rank-sum test or CMH test was used for the categorical data.ResultsWe enrolled 188 patients at 10 medical centers in China (92 assigned to the DES group and 96 to the BMS group). The mean age of the 188 study participants was 61.6 years (range, 38–75 years); 152 participants (80.9%) were male. There were 28 patients (43.8%) with an ISR at 180 days in the BMS group and 10 patients (14.5%) in the DES group [risk difference, 29.3% (95% CI, 14.5%−44.0%); P = 0.001]. The percent of patients with ischemic stroke or TIA in the same territory between 30 days and 1 year was 5.2% (5/96) in the BMS group and 2.2% (2/92) in the DES group [risk difference, 3.0%; (95% CI, −2.3% to 8.2%); P = 0.354]. The percent of patients with successful stent implantation was 99.0% (95/96) in the BMS group and 97.8% (90/92) in the DES group [risk difference, 1.1%; (95% CI, −1.7% to 3.9%); P = 0.584]. In total, five patients (5.2%) in the BMS group and three patients (3.3%) in the DES group [risk difference, 1.9%; (95% CI, −2.3% to 6.1%); P = 0.721] had stroke in any territory and death within the 30-day follow-up. Total adverse events occurred 167 times in 72 patients (75.0%) in the BMS group compared with 114 times in 59 patients (64.1%) in the DES group [risk difference, 10.9%; (95% CI, −0.1% to 21.7%); P = 0.115].ConclusionsAmong patients with symptomatic intracranial arterial stenosis and vertebral artery stenosis, the use of a drug-eluting stent compared with a bare metal stent resulted in a decreased risk of ISR, similar successful stent implantation, and similar adverse events. These findings support the use of a drug-eluting stent for patients with symptomatic intracranial arterial stenosis and vertebral artery stenosis.Clinical Trial Registrationhttp://www.chictr.org.cn/showproj.aspx?proj=148272, identifier: ChiCTR2200055925.

Objective: Rare disease. Background: Myelin oligodendrocyte glycoprotein (MOG)-associated disease (MOGAD) is a recently described inflammatory demyelinating disease of the central nervous system (CNS), which needs to be distinguished from aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG+NMOSD) and multiple sclerosis (MS). Case Report: A 42-year-old woman presenting with loss of vision due to optic neuritis was admitted to the Naval Medical Center in October 2022. She had optic disc edema, blurred visual margins, optic disc pallor, and deficient visual field in both eyes. Cranial magnetic resonance imaging (MRI) showed bilateral optic nerve thickening, tortuosity, and swelling, especially on the right side. Orbital MRI T2 sequence showed the typical "double track sign" change. The titers of MOG-IgG in CSF and serum were 1: 1 (+) and 1: 32 (+) separately, so MOGAD was diagnosed. The primary treatment was intravenous methylprednisolone for 2 weeks, after which the blurred vision improved and MRI showed the optic nerve lesions disappeared. She was discharged and oral corticosteroids were tapered gradually, and 1 month later, the symptom had vanished without recurrence, cranial MRI was normal, and MOG-IgG in CSF and serum were negative. Low-dose oral corticosteroids were continued for 6 months, with no relapse and normal cranial MRI, so we stopped corticosteroid therapy. At 1-year follow-up, the symptoms had not recurred. Conclusions: A 42-year-old woman presented with loss of vision due to optic neuritis and positive antibody testing for MOG. MOGAD was diagnosed, and timely immunotherapy was effective. [ABSTRACT FROM AUTHOR]

Abstract Environmentally sensitive fluorescent probes (including AIEgens) play pivotal roles in numerous biological studies. Many of these functional materials are developed based on the twisted intramolecular charge transfer (TICT) mechanism. However, the TICT tendency of dialkylated amino groups in biocompatible main‐stream fluorophores (i.e., coumarins and rhodamines) is weak, limiting their sensitivities. Herein, by replacing dialkylated amino donors with an N‐methylpyrrole group to enhance TICT, a simple and general method to engineer highly environmentally sensitive fluorescent probes is reported. This method yields a platter of colorful fluorescent probes that demonstrates outstanding polarity and viscosity sensitivity with large turn‐on ratios (up to 191 times for polarity and 14 times for viscosity), as well as distinct aggregation‐induced emission (AIE) characteristics. The utilities of these probes in both wash‐free bioimaging and protein detections are also successfully demonstrated. It is expected that this molecular design strategy will inspire the creation of many environmentally sensitive probes.

Objective To analyze the causes and possible influence factors of endovascular recanalization failure of chronic internal carotid artery occlusion (CICAO). Methods One hundred and three patients with CICAO underwent endovascular recanalization in Department of Interventional Neurology in Beijing Tiantan Hospital, Capital Medical University were selected from December 2012 to December 2019. The factors possibly related to failure (including sex, age, underlying disease, time from occlusionto recanalization, the shape of the stump and the position of the reflux) were analyzed. Univariate and multivariate Logistic regression analysis were used to screen for influence factors related to the failure of recanalization. Results In 103cases,there were33 patients who failed in recanalization, the failurerate was 32.04%. One case (0.97%) occurred subarachnoid hemorrhage which induced severe headache during operation. Logistic regression analysis showed thatthe stump ofthe occluded ICA was non⁃pointed (OR= 3.037, 95%CI: 1.245-7.406; P=0.015) and the reflux position of the distal ICA was above the cavernous sinus (C4-C6 segment; OR =3.118, 95%CI: 1.206-8.061, P =0.019) were the risk factors for failure of successful rate after endovascular recanalization of CICAO. Of the 33 failure cases, 27 cases (81.82%) were due to guide wires failed to pass through the occlusion segment, which mainly occurred in C4-C5 segment (14 cases, 42.42%) and C1 segment (11 cases, 33.33%); other 6 cases (18.18%) were due to dissection which mainly occurred in C4-C5 segment (5 cases, 15.15%). Conclusions Endovascular recanalization of CICAO is relatively safe and feasible. The stump condition and the position of distal reflux of the occlud ed ICA are the key in judging the difficulty of recanalization. DOI：10.3969/j.issn.1672⁃6731.2020.06.005

Acute progressive large vessel occlusive stroke (APLVO) is a special kind of acute ischemic stroke with large vessel occlusion (AIS⁃LVO). Adequate medical history inquiry, detailed imaging analysis and appropriate individualized treatment can lead to better therapeutic effect for APLVO patients. This article reviews the pathophysiological mechanism, clinical features, classification and treatment strategy of APLVO, which different from other causes of ischemic stroke. DOI：10.3969/j.issn.1672⁃6731.2020.05.004

Objective To screen the risk factors related to unfavorable prognosis and evaluate the predictive effect of four imaging scoring systems on the unfavorable prognosis in the patients with acute basilar artery occlusion (BAO) after endovascular thrombectomy. Methods From March 2012 to August 2018, a total of 57 patients with acute BAO were treated with endovascular thrombectomy, preoperative DWI Posterior Circulation Alberta Stroke Program Early CT Score (pc ⁃ ASPECTS), DWI Brain Stem Score (BSS), Posterior Circulation CTA (pc ⁃ CTA) and Basilar Artery CTA (BATMAN) were used. Thrombolysis in Cerebral Infarction (TICI) was used to evaluate the incidence of vascular recanalization. The incidence of symptomatic intracranial hemorrhage (sICH) was recorded within 36 h. The prognosis was evaluated by modified Rankin Scale (mRS) at 3 months. Univariate and multivariate backward Logistic regression analysis were used to screen the risk factors related to the unfavoriable prognosis in the patients with acute BAO after endovascular thrombectomy. Receiver operating characteristic curve (ROC) was used to calculate the area under the curve (AUC), and evaluate the predictive value of DWI pc ⁃ ASPECTS, DWI BSS, pc ⁃ CTA and BATMAN scores for prognosis. Results In 57 patients, 53 patients (92.98% ) had successful recanalization, 2 (3.51%) had partial recanalization, 2 (3.51%) had no recanalization, 3 (5.26%) had sICH, 22 (38.60%) had good prognosis, 35 (61.40%) had poor prognosis, and 14 (24.56%) died. After univariate and multivariate backward Logistic regression analysis, higher NIHSS score on admission ( OR = 0.879, 95% CI: 0.783-0.986; P = 0.028), higher DWI BSS score ( OR = 0.348, 95% CI: 0.177-0.683; P = 0.002) and lower BATMAN score ( OR = 1.549, 95% CI: 1.019-2.353; P = 0.040) were risk factors for unfavorable prognosis of patients with acute BAO after endovascular thrombectomy. ROC analysis of the four radiographic scoring systems showed that the AUC of DWI pc ⁃ ASPECTS, DWI BSS, pc ⁃ CTA and BATMAN score were 0.787 (95% CI: 0.658-0.884, P = 0.000), 0.861 (95% CI: 0.744-0.938, P = 0.000), 0.634 (95% CI: 0.496-0.757, P = 0.091) and 0.698 (95% CI: 0.562-0.813, P = 0.012), respectively. Conclusions Higher NIHSS score on admission, higher DWI BSS score and lower BATMAN score are risk factors for unfavorable prognosis of acute BAO treated with endovascular thrombectomy. DOI：10.3969/j.issn.1672⁃6731.2020.05.006

Five randomized control clinical trials of N Engl J Med showed the efficacy of endovascular treatment (EVT) of acute ischemic stroke with large vessel occlusion (AIS ⁃ LVO) of anterior circulation. The "spring" of mechanical thrombectomy is coming. The international guideline changed and the treatment of AIS ⁃ LVO have been entering a new era. Mechanical thrombectomy became the one of milestones in the treatment of ischemic cerebrovascular events. The year of 2020 is the five years' anniversary since the "spring" of thrombectomy. What have we learned and where are we heading? To mark this anniversary year, this review takes you through the evolution of EVT from its tough beginnings to a way through the dark. DOI：10.3969/j.issn.1672⁃6731.2020.05.002

Objective To evaluate whether patients with acute basilar artery occlusion (BAO) tandem lesion could affect the clinical outcome after receiving endovascular treatment (EVT) in a high ⁃ volume stroke center. Methods A total of 187 consecutive patients with acute BAO receiving EVT from January 2012 to July 2018 were recruited in this study. The patients were categorized into 2 groups with (25 cases) or without (162 cases) tandem lesion. Preoperative Posterior Circulation Alberta Stroke Program Early CT Score (pc ⁃ ASPECTS) and Pons ⁃ Midbrairn Index (PMI) were used to evaluate the cerebral infarction range, and Post ⁃ Traffic Score and American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) grading were used to evaluate the posterior circulation collateral compensation after actue BAO. The main prognostic indicators were immediate postoperative vascular recanalization rate, functional independence and prognosis 90 d after treatment, and the main safety endpoints were intracranial hemorrhage (ICH) and symptomatic intracranial hemorrhage (sICH) incidence 7 d after surgery and mortality 90 d after treatment. Results In tandem group, the lesions were mainly located at the beginning of the basilar artery (including the intracranial segment of the vertebral artery) and at the distal end ( P = 0.000), and the proportion of intracranial arterial stenosis was lower ( P = 0.000). Among the 25 patients with tandem lesion, 21 took the Dirty ⁃ road route and 4 took the Clean ⁃ road route. The proportion of stent thrombectomy ( P = 0.030) and intraoperative intravenous injection of tirofibana ( P = 0.028) was lower, the proportion of stent implantation was higher ( P = 0.005), the proportion of vascular recanalization after treatment was lower ( P = 0.001), and the mortality rate was higher 90 d after treatment ( P = 0.002). Univariate and multivariate Logistic regression analysis showed that acute BAO tandem lesion had a lower immediate vascular recanalization rate ( OR = 0.050, 95% CI: 0.010-0.530; P = 0.012) and a higher mortality 90 d after treatment (OR = 17.320, 95% CI: 2.700-111.040; P = 0.003). Conclusions Tandem lesion seems to be associated with low rate of recanalization and high rate of mortality in patients with acute BAO. DOI：10.3969/j.issn.1672⁃6731.2020.05.005

Platelet glycoprotein (GP) Ⅱ b/Ⅲ a receptor is the final common pathway of platelet aggregation and thrombosis, which can specifically and rapidly inhibit platelet aggregation. In recent years, more and more evidences support that tirofiban, a GP Ⅱ b/Ⅲ a receptor antagonist, can be used as a treatment option for thromboembolic diseases, but its application experience in clinical practice is still relatively insufficient. In order to apply tirofiban more reasonably and normatively in clinical practice, the Chinese Stroke Society organized a writing committee of well ⁃ known experts in the field of neurological intervention in China, and wrote the consensus of experts on the clinical application of tirofiban in atherosclerotic cerebrovascular diseases. It provides clinical experience and guidance for the application of tirofiban in the field of cerebrovascular disease, and guarantees the safe and effective use of drugs in medical behaviors. DOI：10.3969/j.issn.1672⁃6731.2020.05.003

Objective: Inflammatory cytokines are increased during one-lung ventilation in patients undergoing lung resection, and this increase can be fatal. Propofol and sevoflurane are the main anesthetics used for these patients. Unfortunately, there is no consensus on the best choice of an anesthetic agent concerning an inflammatory response in patients undergoing lung resection. This meta-analysis aimed to compare the effects of propofol and sevoflurane on the inflammatory response in patients undergoing lung resection.Methods: We searched electronic databases to identify randomized controlled trials comparing the effects of different anesthetics (sevoflurane vs. propofol) on the inflammatory response. The primary outcome concerned the concentration of systemic inflammatory cytokines. The secondary outcomes concerned the concentrations of inflammatory cytokines in the bronchoalveolar lavage (BAL) fluid from the dependent and independent lung. Random effects analysis of the meta-analyses were performed to synthesize the evidence and to assess the concentrations of inflammatory factors in the sevoflurane and propofol groups.Results: Eight trials involving 488 participants undergoing lung resection with one-lung ventilation were included. There was no significant difference in the concentrations of systemic interleukin (IL)-6, IL-10, or tumor necrosis factor α between the sevoflurane and propofol groups. Compared with the propofol group, BAL levels of IL-6 in the dependent ventilated lung were decreased in the sevoflurane group (three trials, 256 participants; standardized mean difference [SMD], −0.51; 95% confidence interval [CI], −0.90 to −0.11; p = 0.01; I2 = 46%). The BAL levels of IL-6 in the independent ventilated lung were also decreased by sevoflurane (four trials, 362 participants; SMD, −0.70; 95% [CI], −0.93 to −0.47; p < 0.00001; I2 = 0%).Conclusions: There was no difference in the systemic inflammatory response between the sevoflurane and propofol groups. However, compared with propofol, sevoflurane can reduce the local alveolar inflammatory response. Additional research is necessary to confirm whether the inflammatory response is direct or indirect.

The diagnosis and treatment of chronic large vessel occlusion is in its infancy period. At present, few studies reported some successful cases, but on the whole, the opening of large vessel occlusion is in a state of exploration in terms of preoperative evaluation, patient selection, technical methods and also evidence⁃based medicine. With improvement of the experience of multi⁃disciplinary doctors, as well as the updating and iteration of nerve⁃interventional materials, the level of diagnosis and treatment of large vessel occlusion is constantly improving. We focus on the current situation and problems of endovascular treatment of chronic macrovascular occlusion in order to provide valuable experience for the future development of this work. DOI: 10.3969/j.issn.1672⁃6731.2020.06.002

Highbush blueberry is a small berry fruit tree belonging to the family Ericaceae and genus Vaccinium, which fruit has high nutritional value. High-throughput sequencing technology was applied in this study to sequence and assemble the whole chloroplast genome of the southern highbush blueberry variety sharpblue. The results of the study showed that the circular genome of sharpblue is 170,737 bp in length, and the GC content of the genome was 36.8%. The complete chloroplast genome of sharpblue has consisted of two inverted repeat regions (IRs), a large single-copy region (LSC, 31, 076 bp), and a small single-copy region (SSC, 3, 044 bp). The chloroplast genome contained a total of 144 functional genes, including 100 mRNA genes, eight rRNA genes, and 36 tRNA genes. In addition, V. corymbosum and V. oldhamii were clustered into one group in this phylogenetic analysis which indicated that they have a close evolutionary relationship. The findings of this investigation are a significant reference source for the phylogeny and evolutionary origin of the Ericaceae family.

Background: For patients with symptomatic intracranial artery stenosis (sICAS), endovascular treatment has been shown to be feasible and safe in recent studies. However, in-stent restenosis (ISR) risks the recurrence of ischemic stroke. We attempt to elucidate the risk factors for ISR.Methods: We retrospectively analyzed 97 patients with sICAS from a prospective registry trial that included 20 centers from September 2013 to January 2015. Cases were classified into the ISR≥ 50% group or the ISR < 50% group. The baseline characteristics and long-term follow-up were compared between the two groups. Binary logistic regression analyses were identified as an association between ISR and endovascular technique factors.Results: According to whether ISR was detected by CT angiography, 97 patients were divided into the ISR group (n = 24) and the non-ISR group (n = 73). The admission baseline features and lesion angiography characteristics were similar, while plasma hs-CRP (mg/L) was higher in the ISR≥ 50% group at admission (8.2 ± 11.4 vs. 2.8 ± 4.1, p = 0.032). Binary logistic regression analysis identified the longer stents (adjusted OR 0.816, 95% CI 0.699–0.953; p = 0.010), balloon-mounted stents (adjusted OR 5.748, 95% CI 1.533–21.546; p = 0.009), and local anesthesia (adjusted OR 6.000, 95% CI 1.693–21.262; p = 0.006) as predictors of ISR at the 1-year follow-up.Conclusions: The longer stents, balloon-mounted stents implanted in the intracranial vertebral or basilar artery, and local anesthesia were significantly associated with in-stent restenosis. Further studies are required to identify accurate biomarkers or image markers associated with ISR in ICAS patients.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT01968122.

BackgroundM10 is a derivative of Myricetin by adding a hydrophilic glycosylation group. Our previous study revealed that M10 by oral administration prevented colitis-associated colonic cancer (CAC) through attenuating endoplasmic reticulum stress in mice. In current study, we evaluated the inhibitory effects of M10 on ulcerative colitis in mice model, the mechanism of M10 in preventing colitis was further investigated.MethodsMice model of ulcerative colitis was induced by continuous oral dextran sodium sulfate (DSS). M10 was given gavage once a day for 12 consecutive weeks. Disease activity index (DAI) was recorded by analyzing the symptoms of colitis. Intestinal barrier was analyzed by the Immunofluorescence staining assay. The structure of microvilli of intestinal epithelial cells was analyzed under Transmission electron microscopy (TEM). TEM assay was also performed to determine the formation of necroptosis in the colonic epithelium with ulcerative colitis. We performed Western blotting assay to analyze the IL-6 and NF-κB pathways, as well as the cytokine cascades related to TNF-α signaling pathway during necroptosis.ResultsM10 by oral administration demonstrated a prevention of ulcerative colitis, showing a significant decrease of DAI as compared to the model mice. Pathological analysis indicated that M10 attenuated the degree of colonic inflammation in colonic tissues. M10 restored the structures of intestinal barrier damaged by DSS. M10 prevented the activation of the IL-6 and NF-κB signaling pathways in the inflamed colonic epithelium. Further, M10 prevented necroptosis in the inflamed colonic mucosal cells through down-regulating the TNF-α pathway. Importantly, M10 demonstrated higher activities in preventing ulcerative colitis than Myricetin and control drug Mesalazine.ConclusionsMyricetin derivative M10 prevents chronic ulcerative colitis through inhibiting necroptosis. M10 could be developed as a promising drug for the treatment of chronic ulcerative colitis.

For efficient plant reproduction, seed dormancy delays seed germination until the environment is suitable for the next generation growth and development. The phytohormone abscisic acid (ABA) plays important role in the induction and maintenance of seed dormancy. Previous studies have identified that WRKY transcription factors can regulate ABA signaling pathway. Here, we identified an Oswrky29 mutant with enhanced dormancy in a screen of T-DNA insertion population. OsWRKY29 is a member of WRKY transcription factor family which located in the nuclear. The genetic analyses showed that both knockout and RNAi lines of OsWRKY29 had enhanced seed dormancy whereas its overexpression lines displayed reduced seed dormancy. When treated with ABA, OsWRKY29 knockout and RNAi lines showed greater sensitivity than its overexpression lines. In addition, the expression levels of ABA positive response factors OsVP1 and OsABF1 were higher in the OsWRKY29 mutants but were lower in its overexpression lines. Further assays showed that OsWRKY29 could bind to the promoters of OsABF1 and OsVP1 to inhibit their expression. In summary, we identified a new ABA signaling repressor OsWRKY29 that represses seed dormancy by directly downregulating the expression of OsABF1 and OsVP1.

Abstract Posttraumatic stress disorder (PTSD) is a chronic impairment disorder that occurs after exposure to traumatic events. This disorder can result in a disturbance to individual and family functioning, causing significant medical, financial, and social problems. This study is a selective review of literature aiming to provide a general outlook of the current understanding of PTSD. There are several diagnostic guidelines for PTSD, with the most recent editions of the DSM-5 and ICD-11 being best accepted. Generally, PTSD is diagnosed according to several clusters of symptoms occurring after exposure to extreme stressors. Its pathogenesis is multifactorial, including the activation of the hypothalamic–pituitary–adrenal (HPA) axis, immune response, or even genetic discrepancy. The morphological alternation of subcortical brain structures may also correlate with PTSD symptoms. Prevention and treatment methods for PTSD vary from psychological interventions to pharmacological medications. Overall, the findings of pertinent studies are difficult to generalize because of heterogeneous patient groups, different traumatic events, diagnostic criteria, and study designs. Future investigations are needed to determine which guideline or inspection method is the best for early diagnosis and which strategies might prevent the development of PTSD.

Sensitive and rapid identification of illicit drugs in a non-contact mode remains a challenge. Here, the authors report three film-based fluorescent sensors showing remarkable sensitivity, selectivity and response speed to six widely abused illicit drugs in vapor phase.

Pueraria thomsonii is a leguminous plant with high root yield and starch content. It is also a medicinal material in the Chinese pharmacopeia. However, the raw materials of P. thomsonii are often confused with some non-medicinal Pueraria plants. To enrich the genetic resources of P. thomsonii and guide its molecular identification, the complete chloroplast genome was sequenced and reported. The total genome of P. thomsonii is 153,434 bp in length. consisting of two inverted repeat regions (IRS, 25,640 bp each) separated by a large single-copy (LSC, 84,155 bp) and a small single-copy region (SSC, 17,999 bp). The overall GC content is 35.41%. It contains 130 genes, including 85 protein coding genes, 8 rRNA genes and 37 tRNA genes. Phylogenetic analysis showed that P. thomsonii could be distinguished from other plants and closely related to the legume Pachyrhizus erosus. This study enriches the genetic information of P. thomsonii and contributes to the screening of excellent germplasm.