MtPIN4 plays critical roles in amino acid biosynthesis and metabolism of seed in Medicago truncatula.

The regulation of seed development is critical for determining crop yield. Auxins are vital phytohormones that play roles in various aspects of plant growth and development. However, its role in amino acid biosynthesis and metabolism in seeds is not fully understood. In this study, we identified a mutant with small seeds through forward genetic screening in Medicago truncatula. The mutated gene encodes MtPIN4, an ortholog of PIN1. Using molecular approaches and integrative omics analyses, we discovered that auxin and amino acid content significantly decreased in mtpin4 seeds, highlighting the role of MtPIN4-mediated auxin distribution in amino acid biosynthesis and metabolism. Furthermore, genetic analysis revealed that the three orthologs of PIN1 have specific and overlapping functions in various developmental processes in M. truncatula. Our findings emphasize the significance of MtPIN4 in seed development and offer insights into the molecular mechanisms governing the regulation of seed size in crops. This knowledge could be applied to enhance crop quality by targeted manipulation of seed protein regulatory pathways.

Impact of stent retriever size on clinical outcomes in the RECO registry.

Objective: In the RECO study, we investigated the impact of the operator's choice of stent retriever size on patients with internal carotid artery (ICA) occlusion. Methods: Data from the RECO Registry, a prospective multicentre study, were utilized. Patients who underwent mechanical thrombectomy (MT) were divided according to the size of the stent into the RECO 4 × 20 group, the RECO 5 × 30 group and the RECO 6 × 30 group. The outcome measures assessed in the study were the 3-month modified Rankin Scale (mRS) score, occurrence of any intracranial haemorrhage (aICH), workflow timing, recanalization success rate, number of attempts, and all-cause mortality within a 3-month period. Results: Analysis was conducted on a total of 89 patients with ICA occlusion. RECO 4 × 20, 5 × 30, and 6 × 30 stent retrievers were used in 19 (21.3%), 52 (58.4%), and 18 (20.2%) patients, respectively. The demographic and baseline characteristics showed considerable similarity across the three groups. The puncture-to-recanalization time of the RECO 6 × 30 group [56.5 min (IQR, 41.5-80.8)] was significantly shorter than that of the RECO 4 × 20 group [110 min (IQR, 47-135)]. In 10 out of 18 patients (55.6%), the RECO 6 × 30 stent retriever achieved reperfusion (modified Thrombolysis in Cerebral Infarction [mTICI] score 2b-3) after the initial attempt, surpassing the rates of 31.6% in the RECO 4 × 20 group and 32.7% in the RECO 5 × 30 group. In the RECO 4 × 20 group, the median number of passes was 2 (IQR, 1-3); in the RECO 5 × 30 group, it was 2 (IQR, 1-3); and in the RECO 6 × 30 groups, it was 1 (IQR, 1-2.5). There were no statistically significant differences observed among the three groups concerning aICH or good outcomes (mRS score 0-2). Conclusion: Our study demonstrated the practical implications of stent-retriever size selection in the context of the MT for ICA occlusion. The routine use of a RECO 6 × 30 stent retriever holds the potential for early revascularization in clinical practice. The significant reduction in the puncture-to-reperfusion time and the greater first-pass effect associated with this stent size underscore its efficiency in treating ICA occlusion.

Rewiring of a KNOXI regulatory network mediated by UFO underlies the compound leaf development in Medicago truncatula.

Class I KNOTTED-like homeobox (KNOXI) genes are parts of the regulatory network that control the evolutionary diversification of leaf morphology. Their specific spatiotemporal expression patterns in developing leaves correlate with the degrees of leaf complexity between simple-leafed and compound-leafed species. However, KNOXI genes are not involved in compound leaf formation in several legume species. Here, we identify a pathway for dual repression of MtKNOXI function in Medicago truncatula. PINNATE-LIKE PENTAFOLIATA1 (PINNA1) represses the expression of MtKNOXI, while PINNA1 interacts with MtKNOXI and sequesters it to the cytoplasm. Further investigations reveal that UNUSUAL FLORAL ORGANS (MtUFO) is the direct target of MtKNOXI, and mediates the transition from trifoliate to pinnate-like pentafoliate leaves. These data suggest a new layer of regulation for morphological diversity in compound-leafed species, in which the conserved regulators of floral development, MtUFO, and leaf development, MtKNOXI, are involved in variation of pinnate-like compound leaves in M. truncatula.

Exclusively Posterior Circulation Stroke Caused by Internal Carotid Artery Thrombosis.

A fetal posterior cerebral artery (FPCA) is an anatomic variant in which the posterior cerebral artery (PCA) is an embryological derivative of the internal carotid artery (ICA). Patients with FPCA may experience posterior circulation stroke (PCS) after a thrombotic event in the ICA system, while exclusively PCS caused by thrombosis of the ICA has rarely been reported. We report a patient with FPCA and summarize 3 types of exclusively PCS caused by FPCA due to thrombotic events in the ICA system. Type A: the thrombus involves the opening of the FPCA and obstructs the blood flow of the entire ICA. The contralateral ICA compensates the ipsilateral middle cerebral artery (MCA) and anterior cerebral artery (ACA) through the anterior communicating artery (ACOM). Type B: the thrombus involves the opening of the FPCA but does not block the blood flow of the entire ICA, which still perfuses the ipsilateral ACA and MCA. Type C: the thrombus only involves the FPCA and not the ipsilateral ICA. Patients with types A and B may obtain a good prognosis through endovascular treatment (EVT), while the benefits of this procedure in type C patients are unclear.

PPR-DYW Protein EMP17 Is Required for Mitochondrial RNA Editing, Complex III Biogenesis, and Seed Development in Maize.

The conversion of cytidines to uridines (C-to-U) at specific sites in mitochondrial and plastid transcripts is a post-transcriptional processing event that is important to the expression of organellar genes. Pentatricopeptide repeat (PPR) proteins are involved in this process. In this study, we report the function of a previously uncharacterized PPR-DYW protein, Empty pericarp17 (EMP17), in the C-to-U editing and kernel development in maize. EMP17 is targeted to mitochondria. The loss-function of EMP17 arrests maize kernel development, abolishes the editing at ccmF C -799 and nad2-677 sites, and reduces the editing at ccmF C -906 and -966 sites. The absence of editing causes amino acid residue changes in CcmFC-267 (Ser to Pro) and Nad2-226 (Phe to Ser), respectively. As CcmFC functions in cytochrome c (Cytc) maturation, the amount of Cytc and Cytc 1 protein is drastically reduced in emp17, suggesting that the CcmFC-267 (Ser to Pro) change impairs the CcmFC function. As a result, the assembly of complex III is strikingly decreased in emp17. In contrast, the assembly of complex I appears less affected, suggesting that the Nad2-226 (Phe to Ser) change may have less impact on Nad2 function. Together, these results indicate that EMP17 is required for the C-to-U editing at several sites in mitochondrial transcripts, complex III biogenesis, and seed development in maize.

Developmental Analysis of the GATA Factor HANABA TARANU Mutants in Medicago truncatula Reveals Their Roles in Nodule Formation.

Formation of nodules on legume roots results from symbiosis with rhizobial bacteria. Here, we identified two GATA transcription factors, MtHAN1 and MtHAN2, in Medicago truncatula, which are the homologs of HANABA TARANU (HAN) and HANABA TARANU LIKE in Arabidopsis thaliana. Our analysis revealed that MtHAN1 and MtHAN2 are expressed in roots and shoots including the root tip and nodule apex. We further show that MtHAN1 and MtHAN2 localize to the nucleus where they interact and that single and double loss-of-function mutants of MtHAN1 and MtHAN2 did not show any obvious phenotype in flower development, suggesting their role is different than their closest Arabidopsis homologues. Investigation of their symbiotic phenotypes revealed that the mthan1 mthan2 double mutant develop twice as many nodules as wild type, revealing a novel biological role for GATA transcription factors. We found that HAN1/2 transcript levels respond to nitrate treatment like their Arabidopsis counterparts. Global gene transcriptional analysis by RNA sequencing revealed different expression genes enriched for several pathways important for nodule development including flavonoid biosynthesis and phytohormones. In addition, further studies suggest that MtHAN1 and MtHAN2 are required for the expression of several nodule-specific cysteine-rich genes, which they may activate directly, and many peptidase and peptidase inhibitor genes. This work expands our knowledge of the functions of MtHANs in plants by revealing an unexpected role in legume nodulation.

MtPIN1 and MtPIN3 Play Dual Roles in Regulation of Shade Avoidance Response under Different Environments in Medicago truncatula.

Polar auxin transport mediated by PIN-FORMED (PIN) proteins is critical for plant growth and development. As an environmental cue, shade stimulates hypocotyls, petiole, and stem elongation by inducing auxin synthesis and asymmetric distributions, which is modulated by PIN3,4,7 in Arabidopsis. Here, we characterize the MtPIN1 and MtPIN3, which are the orthologs of PIN3,4,7, in model legume species Medicago truncatula. Under the low Red:Far-Red (R:FR) ratio light, the expression of MtPIN1 and MtPIN3 is induced, and shadeavoidance response is disrupted in mtpin1 mtpin3 double mutant, indicating that MtPIN1 and MtPIN3 have a conserved function in shade response. Surprisingly, under the normal growth condition, mtpin1 mtpin3 displayed the constitutive shade avoidance responses, such as the elongated petiole, smaller leaf, and increased auxin and chlorophyll content. Therefore, MtPIN1 and MtPIN3 play dual roles in regulation of shadeavoidance response under different environments. Furthermore, these data suggest that PIN3,4,7 and its orthologs have evolved conserved and specific functions among species.

Effect of butylphthalide on new cerebral microbleeds in patients with acute ischemic stroke.

BACKGROUND: To evaluate the effect of dl-3-N-butylphthalide (NBP) on new cerebral microbleeds (CMBs) in patients with acute ischemic stroke (AIS). METHODS: We will prospectively enroll patients with AIS admitted to the stroke center of Jingjiang People's Hospital. Qualified participants will be randomly assigned to either the NBP group (NBP injection) or the control group (NBP injection placebo) in a ratio of 1:1. Patients will complete the brain magnetic resonance imaging within 48 hours and 14 days after stroke onset to observe the CMBs through susceptibility weighted imaging, and evaluate whether the use of NBP will affect the new CMBs in AIS patients. SPSS 20.0 will be used for statistical analyses. RESULT: We will provide practical and targeted results assessing the safety of NBP for AIS patients, to provide reference for clinical use of NBP. CONCLUSION: The stronger evidence about the effect of NBP on new CMBs in AIS patients will be provided for clinicians.

A right eye amaurosis patient with congenital absence of the internal carotid artery: A care compliant case report.

RATIONALE: Absence or hypoplasia of the internal carotid artery (ICA) are rare developmental anomalies. Usually, patients with ICA agenesis are asymptomatic due to collateral circulation, but they may present with seizures, headache, or transient ischemic attack. We report a patient with right ICA absence in whom "paroxysmal right eye amaurosis" was the main symptom. PATIENT CONCERNS: A 76-year-old male patient suffered from "paroxysmal right eye amaurosis for 3 years". Three years prior, the patient had suffered sudden one-minute right eye amaurosis without any obvious cause. The attack reoccurred 1-2 times/year until one week before admission when he experienced two sudden right eye amaurosis. DIAGNOSIS: Congenital absence of the right ICA was diagnosed. In this patient with congenital absence of the right ICA, the ipsilateral anterior cerebral artery (ACA) was compensated by the anterior communicating artery (ACOM), and the ipsilateral middle cerebral artery (MCA) emerged from the carotid siphon of the contralateral ICA. INTERVENTIONS: The patient was given antiplatelet treatment consisting of aspirin and atorvastatin after admission and instructed to maintain the treatment after discharge. OUTCOMES: No symptom onset was observed during follow-up. LESSONS: Here, we report the patient's clinical manifestations and imaging findings and analyze the cause of the condition to provide a clinical reference for the study of congenital absence of the ICA.

A comparison of sotagliflozin therapy for diabetes mellitus between week 24 with week 52 : A protocol for mixed treatment comparisons meta-analysis.

BACKGROUND: According to the centers for disease control and prevention, 14% of American adults have diabetes - 10% know it, and more than 4% go undiagnosed. Sotagliflozin is a new type of diabetes drug This study is to compare the efficacy of Sotagliflozin therapy for Diabetes Mellitus (DM) between week 24 with week 52. METHODS AND ANALYSIS: Through to October 2019, Web of Science, PubMed Database, Cochrane Library, EMBASE, Clinical Trials and CNKI will be searched to identify randomized controlled trials (RCTs) exploring SOTA therapy for DM. Strict screening and quality evaluation will be performed on the obtained literature independently by 2 researchers; outcome indexes will be extracted. The bias risk of the included studies will be evaluated based on Cochrane assessment tool. Meta-analysis will be performed on the data using Revman 5.3 software. We will provide practical and targeted results assessing the lost efficacy of SOTA therapy for DM from week 24 to week 52, to provide reference for clinicians. ETHICS AND DISSEMINATION: The stronger evidence about the lost efficacy of SOTA for DM from week 24 to week 52 will be provided for clinicians. TRIAL REGISTRATION NUMBER: PROSPERO CRD42019133027. STRENGTHS AND LIMITATIONS OF THIS STUDY: Whether the efficacy of SOTA could last for a long time is still inconclusive, high quality research is still lacking, and this study attempts to explore this issue; The efficacy of SOTA at different times will be compared by direct comparisons and indirect comparisons, this can lead to more accurate and reliable results; The quality of the included literatures are uneven, and some data might be estimated by calculation, which may affect the quality of this study.

Braden scale for assessing pneumonia after acute ischaemic stroke.

BACKGROUND: The prevention of pneumonia is critical for patients with acute ischaemic stroke (AIS). The six subscales in the Braden Scale seem to be related to the occurrence of pneumonia. We aimed to evaluate the feasibility of using the Braden Scale to predict the occurrence of pneumonia after AIS. METHODS: We studied a series of consecutive patients with AIS who were admitted to the hospital. The cohort was subdivided into pneumonia and no pneumonia groups. The scores on the Braden Scale, demographic characteristics and clinical characteristics were obtained and analysed by statistical comparisons between the two groups. We investigated the predictive validity of the Braden Scale by receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 414 patients with AIS were included in this study. Of those 414 patients, 57 (13.8%) patients fulfilled the criteria for post-stroke pneumonia. There were significant differences in age and histories of chronic obstructive pulmonary disease (COPD), dysphagia and Glasgow Coma Scale (GCS) score between the two groups, and the National Institutes of Health Stroke Scale (NIHSS) score in the pneumonia group was significantly higher than that in the no pneumonia group (P < 0.01). The mean score on the Braden Scale in the pneumonia group was significantly lower than that in the no pneumonia group (P < 0.01). The six subscale scores on the Braden Scale were all significantly different between the two groups. The area under the curve (AUC) for the Braden Scale for the prediction of pneumonia after AIS was 0.883 (95% CI = 0.828-0.937). With 18 points as the cutoff point, the sensitivity was 83.2%, and the specificity was 84.2%. CONCLUSION: The Braden Scale with 18 points as the cutoff point is likely a valid clinical grading scale for predicting pneumonia after AIS at presentation. Further studies on the association of the Braden Scale score with stroke outcomes are needed.

Empty Pericarp21 encodes a novel PPR-DYW protein that is required for mitochondrial RNA editing at multiple sites, complexes I and V biogenesis, and seed development in maize.

C-to-U editing is an important event in post-transcriptional RNA processing, which converts a specific cytidine (C)-to-uridine (U) in transcripts of mitochondria and plastids. Typically, the pentatricopeptide repeat (PPR) protein, which specifies the target C residue by binding to its upstream sequence, is involved in the editing of one or a few sites. Here we report a novel PPR-DYW protein EMP21 that is associated with editing of 81 sites in maize. EMP21 is localized in mitochondria and loss of the EMP21 function severely inhibits the embryogenesis and endosperm development in maize. From a scan of 35 mitochondrial transcripts produced by the Emp21 loss-of-function mutant, the C-to-U editing was found to be abolished at five sites (nad7-77, atp1-1292, atp8-437, nad3-275 and rps4-870), while reduced at 76 sites in 21 transcripts. In most cases, the failure to editing resulted in the translation of an incorrect residue. In consequence, the mutant became deficient with respect to the assembly and activity of mitochondrial complexes I and V. As six of the decreased editing sites in emp21 overlap with the affected editing sites in emp5-1, and the editing efficiency at rpl16-458 showed a substantial reduction in the emp21-1 emp5-4 double mutant compared with the emp21-1 and emp5-4 single mutants, we explored their interaction. A yeast two hybrid assay suggested that EMP21 does not interact with EMP5, but both EMP21 and EMP5 interact with ZmMORF8. Together, these results indicate that EMP21 is a novel PPR-DYW protein required for the editing of ~17% of mitochondrial target Cs, and the editing process may involve an interaction between EMP21 and ZmMORF8 (and probably other proteins).

Interhospital transfer on intravenous thrombolysis in patients with acute ischemic stroke in three chinese municipal stroke centers.

We included acute ischemic stroke (AIS) patients who received recombinant tissue plasminogen activator (rt-PA) at three stroke centers via either interhospital transfer or direct presentation and compared the clinical outcomes and time metrics to analyze the impact of interhospital transfer on intravenous thrombolysis (IVT). We retrospectively enrolled patients with AIS admitted to three stroke centers from October 1, 2016, to June 1, 2018. Patients treated with rt-PA were classified into the transfer and direct groups. We collected the patients' general information and time points. Statistical analyses were conducted to examine differences in the clinical outcomes and time metrics between the two groups. A total of 326 patients were enrolled, including 84 patients in the transfer group and 242 in the direct group. The transfer group had a longer onset-to-door time (OTD) (124.5 ± 50.6 min versus 83.2 ± 47.2 min, P < 0.01) but a shorter door-to-needle time (DNT) (53.0 ± 26.3 min versus 81.5 ± 31.1 min, P < 0.01), and the stroke onset-to-needle time was 177.4 ± 51.0 min versus 164.7 ± 53.3 min (P = 0.057). Compared with the direct group, the transfer group achieved similar modified Rankin scale (mRS) 0-2 outcomes (59.5% versus 58.7%, P = 0.768). Interhospital transfer was not an independent risk factor associated with a poor outcome at 90 days. In three Chinese municipal stroke centers, patients with an AIS referral have a longer OTD but a shorter DNT. DNTs of municipal hospitals were far longer than the current international standard, and their improvement is an important task.

CYP2C19 polymorphism and antiplatelet effects of clopidogrel in Chinese stroke patients.

Recently published data indicate that CYP2C19*2 allele is the major determinant of metabolic bioactivation of clopidogrel and thereby variability of antiplatelet effect of clopidogrel in white or black patients undergoing elective coronary stent placement. The conclusion may not be fully generalized or extrapolated to the Chinese people due to significantly higher frequencies of the CYP2C19*2 or *3 variant alleles. We sought to investigate whether the CYP2C19*2 or *3 alleles affects platelet reactivity of clopidogrel in Chinese stroke patients. The study included 183 consecutive Chinese stroke patients after loading with clopidogrel 300 mg. Platelet function was assessed by adenosine diphosphate-induced (ADP 20 micromol/L) platelet aggregation and by light transmittance aggregometry (LTA) after seven 75-mg maintenance doses of clopidogrel before discharge. CYP2C19*2 or *3 genotypes were determined by time-of-flight mass spectrometer (MALDI/TOF-MS). In those patients who were carriers of 1 mutant allele (mutant heterozygotes, CYP2C19*1/*2 or *1/*3), ADP-induced maximum platelet aggregation (MPA) were significantly different compared with wild-type homozygous patients [37.2% (IQR, 19.6 to 50.5%) versus 23.6% (IQR, 14.0 to 35.4%), respectively; P=0.002]. In addition, in the patients who were carriers of 2 mutant allele (mutant homozygotes, CYP2C19*2/*2, *2/*3 or *3/*3,), MPA were also significantly different compared with wildtype homozygous patients [35.7% (IQR, 21.0 to 78.1%) versus 23.6% (IQR, 14.0 to 35.4%, respectively; P = 0.039]. By multivariable linear regression, CYP2C19*2 or *3 loss-of-function alleles were independently associated with ADP-induced MPA measurements (partial R2 = 0.138, P = 0.001). CYP2C19*2 or *3 allele does link to increased MPA and clopidogrel response.