INTAC endonuclease and phosphatase modules differentially regulate transcription by RNA polymerase II.

Gene expression in metazoans is controlled by promoter-proximal pausing of RNA polymerase II, which can undergo productive elongation or promoter-proximal termination. Integrator-PP2A (INTAC) plays a crucial role in determining the fate of paused polymerases, but the underlying mechanisms remain unclear. Here, we establish a rapid degradation system to dissect the functions of INTAC RNA endonuclease and phosphatase modules. We find that both catalytic modules function at most if not all active promoters and enhancers, yet differentially affect polymerase fate. The endonuclease module induces promoter-proximal termination, with its disruption leading to accumulation of elongation-incompetent polymerases and downregulation of highly expressed genes, while elongation-competent polymerases accumulate at lowly expressed genes and non-coding elements, leading to their upregulation. The phosphatase module primarily prevents the release of paused polymerases and limits transcriptional activation, especially for highly paused genes. Thus, both INTAC catalytic modules have unexpectedly general yet distinct roles in dynamic transcriptional control.

R-loop-dependent promoter-proximal termination ensures genome stability.

The proper regulation of transcription is essential for maintaining genome integrity and executing other downstream cellular functions1,2. Here we identify a stable association between the genome-stability regulator sensor of single-stranded DNA (SOSS)3 and the transcription regulator Integrator-PP2A (INTAC)4-6. Through SSB1-mediated recognition of single-stranded DNA, SOSS-INTAC stimulates promoter-proximal termination of transcription and attenuates R-loops associated with paused RNA polymerase II to prevent R-loop-induced genome instability. SOSS-INTAC-dependent attenuation of R-loops is enhanced by the ability of SSB1 to form liquid-like condensates. Deletion of NABP2 (encoding SSB1) or introduction of cancer-associated mutations into its intrinsically disordered region leads to a pervasive accumulation of R-loops, highlighting a genome surveillance function of SOSS-INTAC that enables timely termination of transcription at promoters to constrain R-loop accumulation and ensure genome stability.

SPT5 stabilizes RNA polymerase II, orchestrates transcription cycles, and maintains the enhancer landscape.

Transcription progression is governed by multitasking regulators including SPT5, an evolutionarily conserved factor implicated in virtually all transcriptional steps from enhancer activation to termination. Here we utilize a rapid degradation system and reveal crucial functions of SPT5 in maintaining cellular and chromatin RNA polymerase II (Pol II) levels. Rapid SPT5 depletion causes a pronounced reduction of paused Pol II at promoters and enhancers, distinct from negative elongation factor (NELF) degradation resulting in short-distance paused Pol II redistribution. Most genes exhibit downregulation, but not upregulation, accompanied by greatly impaired transcription activation, altered chromatin landscape at enhancers, and severe Pol II processivity defects at gene bodies. Phosphorylation of an SPT5 linker at serine 666 potentiates pause release and is antagonized by Integrator-PP2A (INTAC) targeting SPT5 and Pol II, while phosphorylation of the SPT5 C-terminal region links to 3' end termination. Our findings position SPT5 as an essential positive regulator of global transcription.

The water lily genome and the early evolution of flowering plants.

Water lilies belong to the angiosperm order Nymphaeales. Amborellales, Nymphaeales and Austrobaileyales together form the so-called ANA-grade of angiosperms, which are extant representatives of lineages that diverged the earliest from the lineage leading to the extant mesangiosperms1-3. Here we report the 409-megabase genome sequence of the blue-petal water lily (Nymphaea colorata). Our phylogenomic analyses support Amborellales and Nymphaeales as successive sister lineages to all other extant angiosperms. The N. colorata genome and 19 other water lily transcriptomes reveal a Nymphaealean whole-genome duplication event, which is shared by Nymphaeaceae and possibly Cabombaceae. Among the genes retained from this whole-genome duplication are homologues of genes that regulate flowering transition and flower development. The broad expression of homologues of floral ABCE genes in N. colorata might support a similarly broadly active ancestral ABCE model of floral organ determination in early angiosperms. Water lilies have evolved attractive floral scents and colours, which are features shared with mesangiosperms, and we identified their putative biosynthetic genes in N. colorata. The chemical compounds and biosynthetic genes behind floral scents suggest that they have evolved in parallel to those in mesangiosperms. Because of its unique phylogenetic position, the N. colorata genome sheds light on the early evolution of angiosperms.

Evaluation of ankle brachial index, serum miR-103 and LP-PLA2 in the prognosis of acute ischemic stroke.

Objective: To explore the prognostic value of ankle brachial index (ABI), serum microribonucleic acid-103 (miR-103), and lipoprotein associated phospholipase A2 (LP-PLA2) indicators in patients with acute ischemic stroke (AIS). Methods: A retrospective analysis was conducted using the medical records of 202 patients with AIS admitted to the First Affiliated Hospital of Hebei North University from June 2019 to December 2022. Patients were divided into two groups based on their prognosis: the Poor-group (n=72) and the Good-group (n=130). Levels of ABI, serum miR-103, and LP-PLA2 indicators were compared between the two groups. Multivariate logistic regression analysis was used to analyze the independent risk factors for the poor prognosis in patients with AIS, and the receiver operating characteristic (ROC) curve was used to evaluate the predictive ability of ABI, serum miR-103, and LP-PLA2 levels on the prognosis of AIS. Results: Seventy two patients had a poor prognosis (35.6%) and 130 had a good prognosis (64.4%). The Poor-group had a higher proportion of elderly patients, patients with a history of diabetes and hypertension, abnormal ABI, and elevations in serum miR-103 and LP-PLA2 compared to the Good-group (P<0.05). Multivariate logistic regression analysis showed that abnormal ABI, and high levels of serum miR-103 and LP-PLA2 were independent risk factors for the poor prognosis. ROC curve provided a combined AUC of 0.862, which was higher than that of the individual ABI, serum miR-103, and LP-PLA2 curves, with values of 0.625, 0.749, and 0.696, respectively (P<0.05). Conclusions: Abnormal ABI, and high serum miR-103 and LP-PLA2 levels are independent risk factors for poor prognosis in AIS patients. They can be used as important indicators for predicting the prognosis of AIS.

Longitudinal variation of circulating Inc-ITSN1-2: A novel biomarker reflecting disease severity, inflammation, recurrence, and death risk in acute ischemic stroke patients.

BACKGROUND: Long noncoding RNA intersectin 1-2 (lnc-ITSN1-2) regulates inflammation and neuronal apoptosis; meanwhile, the latter two factors participate in the pathogenesis of acute ischemic stroke (AIS). Therefore, this study detected lnc-ITSN1-2 at multiple time points, aiming to explore its longitudinal variation and clinical value in the management of AIS patients. METHODS: The current study enrolled 102 AIS patients, then detected their lnc-ITSN1-2 in peripheral blood mononuclear cell (PBMC) at baseline (D0), day (D)1, D3, D7, month (M)1, M3, M6, and year (Y)1 after admission using RT-qPCR. Additionally, lnc-ITSN1-2 in PBMC of 50 controls was also detected. RESULTS: Lnc-ITSN1-2 was up-regulated in AIS patients than that in controls (p < 0.001). Lnc-ITSN1-2 positively associated with NIHSS score, TNF-α, and IL-17A (all p < 0.050) but was not linked with IL-6 (p = 0.093) in AIS patients. Notably, lnc-ITSN1-2 was gradually increased from D0 to D3; while it switched to decrease from D3 to Y1 in AIS patients. Lnc-ITSN1-2 disclosed similar longitudinal variation during 1 year in non-recurrent (p < 0.001), recurrent (p = 0.001), and survived patients (p < 0.001), while the variation of lnc-ITSN1-2 in died patients was not obvious (p = 0.132). More importantly, lnc-ITSN1-2 at D0, D3, D7, M1, M3, M6, and Y1 was higher in recurrent AIS patients than that in non-recurrent AIS patients (all p < 0.050); moreover, lnc-ITSN1-2 at D3, D7, M1, M3, and M6 was up-regulated in died AIS patients than AIS survivors (all p < 0.050). CONCLUSION: The dynamic variation of Inc-ITSN1-2 could serve as a biomarker reflecting disease severity, inflammatory cytokines, recurrence, and death risk in AIS patients.

The role of blood lnc-ZFAS1 in acute ischemic stroke: correlation with neurological impairment, inflammation, and survival profiles.

BACKGROUND: Long non-coding RNA zinc finger antisense 1 (lnc-ZFAS1) has been reported to inhibit neuronal damage in acute ischemic stroke (AIS). However, the role of lnc-ZFAS1 in AIS patients remains unclear. Therefore, we assessed the relationship of lnc-ZFAS1 with neurological impairment, inflammation, and prognosis in AIS patients. METHODS: Totally, 241 AIS patients and 120 controls were enrolled. lnc-ZFAS1 in peripheral blood mononuclear cells was evaluated using reverse transcription-quantitative polymerase chain reaction. Besides, a 3-year follow-up was conducted to assess recurrence-free survival (RFS) and overall survival (OS) in AIS patients. RESULTS: lnc-ZFAS1 was reduced in AIS patients compared to that in controls (Z = -10.693, p < 0.001). In AIS patients, lnc-ZFAS1 was negatively correlated with National Institutes of Health Stroke Scale score (rs  = -0.335, p < 0.001), C-reactive protein (rs  = -0.284, p < 0.001), tumor necrosis factor-alpha (rs  = -0.293, p < 0.001), interleukin-1ß (rs  = -0.149, p = 0.021), and interleukin-6 (rs  = -0.161, p = 0.012), but not underlying diseases (all p > 0.05). Besides, lnc-ZFAS1 was divided into high and low levels based on the median expression in AIS patients. Indeed, high lnc-ZFAS1 predicted better RFS (χ2  = 6.222, p = 0.013); the 1-year, 2-year, and 3-year RFS rates were 94.2%, 88.3%, and 85.5%, respectively, in patients with high lnc-ZFAS1, then 87.5%, 79.2%, and 71.6%, respectively, in those with low lnc-ZFAS1. However, lnc-ZFAS1 was not correlated with OS (χ2  = 1.404, p = 0.236); the 1-year, 2-year, and 3-year OS rates were 98.3%, 95.8%, and 94.0%, respectively, in patients with high lnc-ZFAS1, then 96.7%, 93.9%, and 89.6%, respectively, in those with low lnc-ZFAS1. CONCLUSION: Lower lnc-ZFAS1 expression is connected with increased neurological impairment and inflammation as well as worse RFS in AIS patients.

A high-quality Brassica napus genome reveals expansion of transposable elements, subgenome evolution and disease resistance.

Rapeseed (Brassica napus L.) is a recent allotetraploid crop, which is well known for its high oil production. Here, we report a high-quality genome assembly of a typical semi-winter rapeseed cultivar, 'Zhongshuang11' (hereafter 'ZS11'), using a combination of single-molecule sequencing and chromosome conformation capture (Hi-C) techniques. Most of the high-confidence sequences (93.1%) were anchored to the individual chromosomes with a total of 19 centromeres identified, matching the exact chromosome count of B. napus. The repeat sequences in the A and C subgenomes in B. napus expanded significantly from 500 000 years ago, especially over the last 100 000 years. These young and recently amplified LTR-RTs showed dispersed chromosomal distribution but significantly preferentially clustered into centromeric regions. We exhaustively annotated the nucleotide-binding leucine-rich repeat (NLR) gene repertoire, yielding a total of 597 NLR genes in B. napus genome and 17.4% of which are paired (head-to-head arrangement). Based on the resequencing data of 991 B. napus accessions, we have identified 18 759 245 single nucleotide polymorphisms (SNPs) and detected a large number of genomic regions under selective sweep among the three major ecotype groups (winter, semi-winter and spring) in B. napus. We found 49 NLR genes and five NLR gene pairs colocated in selective sweep regions with different ecotypes, suggesting a rapid diversification of NLR genes during the domestication of B. napus. The high quality of our B. napus 'ZS11' genome assembly could serve as an important resource for the study of rapeseed genomics and reveal the genetic variations associated with important agronomic traits.

How long is the interval over which trial-to-trial effects on Fitts' Law task can operate?

Fitts' Law is a well-studied principle in psychology which holds that movement time (MT) varies with the size and distance of a target across a wide range of tasks. In a recent study, the authors demonstrated that performance on a current trial in a Fitts' Law paradigm is affected by what happens during the previous trial (Tang et al. in Psychon Bull Rev 25(5):1833-1839, 2018). The aim of the present study was to explore how long this trial-to-trial transfer might last and whether or not the transfer would occur between the left and right hands. A series of experiments was carried out using discrete trials, a paradigm in which the current authors and others have previously established that Fitts' Law operates (Fitts and Peterson in J Exp Psychol 67(2):103-112, 1964; Tang et al. 2018). Three inter-trial intervals (3 s, 4 s, and 5 s) were used in separate testing sessions, the order of which was counterbalanced across participants. In addition, trial-to-trial transfer was tested within a single hand and between hands. The results demonstrate that transfer from one trial to the next could bridge 4 s when either the right or the left hand was used and would disappear by 5 s. Moreover, the effect transferred between the two hands. The endpoint accuracy of the current trial was not affected by the previous trial. These findings suggest that the trial-to-trial effect reduces over time and that the transfer of sensorimotor memory or the task set is independent of the particular hand used.

Genome Data of Fusarium oxysporum f. sp. cubense Race 1 and Tropical Race 4 Isolates Using Long-Read Sequencing.

Fusarium wilt of banana is caused by the soilborne fungal pathogen Fusarium oxysporum f. sp. cubense. We generated two chromosome-level assemblies of F. oxysporum f. sp. cubense race 1 and tropical race 4 strains using single-molecule real-time sequencing. The F. oxysporum f. sp. cubense race 1 and tropical race 4 assemblies had 35 and 29 contigs with contig N50 lengths of 2.08 and 4.28 Mb, respectively. These two new references genomes represent a greater than 100-fold improvement over the contig N50 statistics of the previous short-read-based F. oxysporum f. sp. cubense assemblies. The two high-quality assemblies reported here will be a valuable resource for the comparative analysis of F. oxysporum f. sp. cubense races at the pathogenic level.

[A review on behavior and brain imaging research of human visually-guided action].

Bipedalism (using only two legs for walking) and having the capability to use tools have long been considered characteristic features that differentiate human beings from animals. Being able to walk upright freed up human hands, allowing us to reach, grasp, carry food, make and use tools, which greatly increased the survivability of our ancestors. Hand actions not only involve muscles and joints to execute actions but also require computations in the brain to analyze the visual environment and select the appropriate action, as well as formulate the action before execution and correct it in real-time during execution. Here, we review the behavioral and brain imaging research of human hand actions from a perspective of cognitive neuroscience. The review includes the research contents and methods of visually-guided action, existing theories, current debates, new evidence of existing theories, and the applications of action research in robotics and artificial intelligence.

Effects of alteplase and aspirin on functional outcomes in patients with acute ischemic stroke and mild non-disabling neurological deficit.

Investigate the effect of Alteplase and Aspirin on the functional outcomes of patients with acute ischemic stroke with mild non-disabling neurological deficit. In this single-center, randomized controlled study, we selected 60 patients with acute ischemic stroke with mild non-disabling neurological deficit admitted to our hospital from January 2021 to January 2022, and randomly divided them into the study group (n = 30) and the control group (n = 30), the control group was given the Aspirin treatment, the study group was given the Alteplase treatment, and the changes in neurological recovery, daily living ability, exercise ability, balance ability, cognitive function, and short-term prognosis outcomes were observed in these 2 groups. The factors influencing the short-term outcome of Alteplase therapy in patients with acute ischemic stroke were analyzed. The National Institutes of Health Neurological Deficit Score (NIHSS) scores at T1 and T2 of the study group were lower than those in the control group, but the scores of Barthel indicators (BI), Fugl-Meyer Motor Assessment Scale (FMA), Berg Balance Scale (BBS) and Montreal Cognitive Assessment Scale (MoCA) of the study group were higher than those in the control group, and the difference was statistically significant (P < .05). The short-term prognostic outcomes of these 2 groups were not significantly different (P > .05). The effect of the use of Alteplase or Aspirin on short-term functional outcomes in patients with acute ischemic stroke and mild non-disabling neurological deficit is not much different.

Relationship between serum HIF-1α and VEGF levels and prognosis in patients with acute cerebral infarction combined with cerebral-cardiac syndrome.

Objective: This research was conducted to discuss the recent prognosis of patients with acute cerebral infarction (ACI) combined with cerebral-cardiac syndrome (CCS). Method: Eighty-seven patients with ACI were selected, which were divided into the ACI group (52 patients) and the CCS group (35 patients) according to whether the CCS was combined, and another 30 health controls were selected as the control group. Serum hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) levels of subjects in each group at the 1st day, the 3rd day, and the 7th day after admission were measured by enzyme-linked immunosorbent assay. After discharge for 30 days, the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS) score were utilized to evaluate the prognosis of patients. The role of serum HIF-1α and VEGF levels in the prognosis of ACI combined with CCS patients was assessed by receiver operating characteristic curve and the binary logistic regression analysis. Results: Higher serum HIF-1α and VEGF levels were observed in the CCS and ACI groups versus the control group, and the levels of which were even higher in the CCS group in comparison to the ACI group. According to the prognosis of the NIHSS score, fasting blood glucose (FBG), Acute Physiology and Chronic Health Evaluation II score, creatine kinase-MB (CK-MB), and HIF-1α and VEGF levels at the 7th day of admission were higher while Glasgow coma scale (GCS) score was lower in the poor prognosis group than those in the good prognosis group, and the area under the curve (AUC) of serum HIF-1α and VEGF levels was 0.895 (95% confident interval [CI], 0.786-1.000), and 0.855 (95% CI, 0.731-0.980). According to the prognosis of the mRS score, FBG, CK-MB, and HIF-1α and VEGF levels at the 7th day of admission were higher while GCS score was lower in the poor prognosis group than those in the good prognosis group, and the AUC of serum HIF-1α and VEGF levels was 0.850 (95% CI, 0.722-0.979) and 0.901 (95% CI, 0.798-1.000). The results of the binary logistic regression analysis revealed that HIF-1α and VEGF levels may be independent risk factors influencing the prognosis of ACI combined with CCS. Conclusion: Serum HIF-1α and VEGF have a good predictive value for assessing the recent prognosis of patients with ACI combined with CCS, which could be independent risk factors influencing the prognosis of disease.

The pleiotropic roles of SPT5 in transcription.

Initially discovered by genetic screens in budding yeast, SPT5 and its partner SPT4 form a stable complex known as DSIF in metazoa, which plays pleiotropic roles in multiple steps of transcription. SPT5 is the most conserved transcription elongation factor, being found in all three domains of life; however, its structure has evolved to include new domains and associated posttranslational modifications. These gained features have expanded transcriptional functions of SPT5, likely to meet the demand for increasingly complex regulation of transcription in higher organisms. This review discusses the pleiotropic roles of SPT5 in transcription, including RNA polymerase II (Pol II) stabilization, enhancer activation, Pol II pausing and its release, elongation, and termination, with a focus on the most recent progress of SPT5 functions in regulating metazoan transcription.

Improving the Use of Blockchain Technology in Stroke Care Information Management Systems.

Blockchain is a new and popular technology in the digital age. Blockchain technology is referred to as decentralised and distributed digital ledgers, which are called blocks. These blocks are linked together with the cryptographic hashes and are used to record transactions between many computers. No single block can be altered without altering the related blocks. Modification of individual block data is impossible because each block contains information from the previous block. This is the unique strength of blockchain. Timestamps and hashes are some of the important terms when blockchains are considered. Data security is guaranteed with this advanced technology. Blockchain technology finds its application in the healthcare industry with many advantages in a queue. Medical data can be transferred safely and securely for fool-proof management of the medicine supply chain, which helps in healthcare research. Blockchains are used to securely encrypt a patient's information in the event of an outbreak of a pandemic disease. A stroke is referred to as a brain attack, also called cerebral infarction. A cerebral infarction is a sudden stoppage of blood flow in the blood vessels connected to the brain. This study focused on evaluating the application of blockchain technology in Stroke Nursing Information Management Systems. This emerging technology is already in use in the healthcare industry. The patient's data is kept decentralized, transparent, and mainly incorruptible, thus keeping it secured and sharing of data is quick.

Magnetic Resonance Images, Pathological Features of Thrombus, and Expression of NLRP Inflammasome in Patients with Acute Ischemic Stroke.

The aim of this study was to investigate imaging features of magnetic resonance imaging (MRI), pathological features of thrombus, and expression of nucleotide-binding oligomerization domain-like receptors protein 3 (NLRP3) inflammasome in acute ischemic stroke (AIS). Their relationship with the prognosis of patients was also explored. Sixty patients with AIS admitted to the hospital were selected as the observation group, and 20 healthy objects were in the control group. The shape of the thrombus was observed by MRI, pathological features of the thrombus were observed under hematoxylin-eosin (HE) staining, and the levels of NLRP3 inflammasome and inflammatory factors in serum were detected. The MRI-T2 weighted imaging (T2WI) signal ratio and plaque enhancement rate in the observation group were higher than those in the control group significantly (P < 0.05). In the observation group, the red/mixed thrombus in 6-12 h and 24 h were also much higher than that in 6 h (P < 0.05). The levels of NLRP3, interleukin-1ß (IL-1ß), interleukin-18 (IL-18), and tumor necrosis factor-α (TNF-α) in the observation group were higher than those in the control group in 6 h, 6-12 h, and 24 h (P < 0.05), and those reached the highest levels in 24 h. The ratio of fibrins/platelets in the cardiogenic thrombus reached (63.8 ± 15.6) %, which was significantly higher than that in the large-artery atherosclerotic thrombus (49.5 ± 14.2) %, P < 0.05. The ratio of red blood cells (RBCs) in the large atherosclerotic thrombus was (30.7 ± 14.3) %, considerably lower than (42.9 ± 15.2) %, P < 0.05. The prognosis of patients with the fibrin/platelet-rich thrombus was highly lower than that with the RBC-rich thrombus (P < 0.05). The levels with poor prognosis were higher than those with good prognosis (P < 0.05). MRI could be used to assist in the assessment of brain conditions in patients with AIS. NLRP3 inflammasome was involved in the inflammatory response of AIS and can be used for predicting the poor prognosis, having a certain clinical application value. In addition, different types of thrombi also laid a certain impact on prognosis.

Application of Integrated Emergency Care Model Based on Failure Modes and Effects Analysis in Patients With Ischemic Stroke.

Purpose: To explore the application value of an integrated emergency care model based on failure modes and effects analysis (FMEA) in patients with acute ischemic stroke (AIS). Methods: According to the convenience sampling method, 100 patients with AIS who visited the emergency department in our hospital from October 2018 to March 2019 were randomly selected as the control group and received routine emergency care mode intervention. Another 100 AIS patients who visited the emergency department from April to October 2019 were selected as the intervention group and received the integrated emergency care model based on FMEA. The total time spent from admission to completion of each emergency procedure [total time spent from admission to emergency physician reception (T0-1), total time spent from admission to stroke team reception (T0-2), total time spent from admission to imaging report out (T0-3), total time spent from admission to laboratory report out (T0-4), and total time spent from admission to intravenous thrombolysis (T0-5)] was recorded for both groups. The clinical outcome indicators (vascular recanalization rate, symptomatic intracerebral hemorrhage incidence, mortality rate) were observed for both groups. The National Institutes of Health Stroke Scale (NIHSS) score and Barthel score were evaluated for both groups after the intervention. The treatment satisfaction rate of the patients was investigated for both groups. Results: The total time of T0-1, T0-2, T0-3, T0-4, T0-5 in the intervention group (0.55 ± 0.15, 1.23 ± 0.30, 21.24 ± 3.01, 33.30 ± 5.28, 44.19 ± 7.02) min was shorter than that of the control group (1.22 ± 0.28, 4.01 ± 1.06, 34.12 ± 4.44, 72.48 ± 8.27, 80.31 ± 9.22) min (P < 0.05). The vascular recanalization rate in the intervention group (23.00%) was higher than that in the control group (12.00%) (P < 0.05). There was no statistical significance in the symptomatic intracerebral hemorrhage incidence and mortality rate in the two groups (P > 0.05). After intervention, the NIHSS score of the intervention group (2.95 ± 0.91) was lower than that of the control group (6.10 ± 2.02), and the Barthel score (77.58 ± 7.33) was higher than that of the control group (53.34 ± 5.12) (P < 0.05). The treatment satisfaction rate in the intervention group (95.00%) was higher than that of the control group (86.00%) (P < 0.05). Conclusion: Through FMEA, the failure mode that affects the emergency time of AIS patients is effectively analyzed and the targeted optimization process is proposed, which are important to enhance the efficiency and success rate of resuscitation of medical and nursing staff and improve the prognosis and life ability of patients.

Construction of a Health Management Model for Early Identification of Ischaemic Stroke in Cloud Computing.

Knowledge discovery and cloud computing can help early identification of ischaemic stroke and provide intelligent, humane, and preventive healthcare services for patients at high risk of stroke. This study proposes constructing a health management model for early identification and warning of ischaemic stroke based on IoT and cloud computing, and discusses its connotation, constructive ideas, and research content so as to provide reference for its health management in order to develop and implement countermeasures and to compare the awareness of early stroke symptoms and first aid knowledge among stroke patients and their families before and after the activity. The rate of awareness of early symptoms and first aid among stroke patients and their families increased from 36% to 78%, and the difference was statistically significant (P < 0.05) before and after the activity.

Endovascular treatment vs drug therapy alone in patients with mild ischemic stroke and large infarct cores.

BACKGROUND: Treatment decision making is strictly associated with the outcomes in patients with ischemic stroke who show a large core infarct. Medical care alone may result in suboptimal treatment efficacy, and endovascular treatment may be accompanied by safety issues. Whether endovascular treatment is superior to medical care is not well investigated in the clinical studies. AIM: To investigate the efficacy of endovascular treatment and drug therapy alone in mild ischemic stroke patients with large infarct cores. METHODS: Fifty patients with mild ischemic stroke and 50 patients with acute ischemic stroke caused by anterior large vessel occlusion were selected at the First Affiliated Hospital of Hebei North University between January 2021 and December 2021. Patients were divided into an endovascular therapy group and a drug therapy group according to different treatment methods. In the endovascular therapy group, there were 28 patients with minor stroke and 22 patients with large infarct cores. The drug therapy group had 22 patients with minor stroke and 28 patients with large infarct cores. The National Institutes of Health Stroke Scale (NIHSS) scores were collected and compared between the two groups immediately after the operation and 24 h and 7 d after the operation. The modified Rankin scale (mRS) and/or activity of daily living were assessed at hospital discharge. RESULTS: There was no significant difference in NIHSS scores between the two groups before the operation (P > 0.05). NIHSS scores were lower in the endovascular therapy group than in the drug therapy group at 24 h and 7 d after the operation and at hospital discharge (all P < 0.05). The incidence of early neurologic deterioration was significantly lower in the endovascular therapy group than in the drug therapy group (P < 0.05). At hospital discharge, the mRS score was lower in the endovascular treatment group than in the drug therapy group, and the activity of daily living score was better in the endovascular treatment group than in the drug therapy group (all P < 0.05). During a follow-up of 3 mo, 17 patients (34.0%) had good prognosis (mRS ≤ 2), 33 patients (66.0%) had poor prognosis (mRS > 2), and 11 patients (22.0%) died. In the medical treatment group, 16 patients (mRS ≤ 2) had good prognosis (32.0%), 34 patients (mRS > 2) had poor prognosis (68.0%), and 14 patients (28.0%) died. There was no significant difference in prognosis and mortality between the two groups (P > 0.05). CONCLUSION: Endovascular therapy can improve NIHSS score and mRS score in patients with mild ischemic stroke and large infarct cores. It is suitable for clinical application.

RPAP2 regulates a transcription initiation checkpoint by inhibiting assembly of pre-initiation complex.

RNA polymerase II (Pol II)-mediated transcription in metazoans requires precise regulation. RNA Pol II-associated protein 2 (RPAP2) was previously identified to transport Pol II from cytoplasm to nucleus and dephosphorylates Pol II C-terminal domain (CTD). Here, we show that RPAP2 binds hypo-/hyper-phosphorylated Pol II with undetectable phosphatase activity. The structure of RPAP2-Pol II shows mutually exclusive assembly of RPAP2-Pol II and pre-initiation complex (PIC) due to three steric clashes. RPAP2 prevents and disrupts Pol II-TFIIF interaction and impairs in vitro transcription initiation, suggesting a function in inhibiting PIC assembly. Loss of RPAP2 in cells leads to global accumulation of TFIIF and Pol II at promoters, indicating a critical role of RPAP2 in inhibiting PIC assembly independent of its putative phosphatase activity. Our study indicates that RPAP2 functions as a gatekeeper to inhibit PIC assembly and transcription initiation and suggests a transcription checkpoint.