Identification of m6A/m5C-related lncRNA signature for prediction of prognosis and immunotherapy efficacy in esophageal squamous cell carcinoma.

N6-methyladenosine (m6A) and 5-methylcytosine (m5C) RNA modifications have garnered significant attention in the field of epigenetic research due to their close association with human cancers. This study we focus on elucidating the expression patterns of m6A/m5C-related long non-coding RNAs (lncRNAs) in esophageal squamous cell carcinoma (ESCC) and assessing their prognostic significance and therapeutic potential. Transcriptomic profiles of ESCC were derived from public resources. m6A/m5C-related lncRNAs were obtained from TCGA using Spearman's correlations analysis. The m6A/m5C-lncRNAs prognostic signature was selected to construct a RiskScore model for survival prediction, and their correlation with the immune microenvironment and immunotherapy response was analyzed. A total of 606 m6A/m5C-lncRNAs were screened, and ESCC cases in the TCGA cohort were stratified into three clusters, which showed significantly distinct in various clinical features and immune landscapes. A RiskScore model comprising ten m6A/m5C-lncRNAs prognostic signature were constructed and displayed good independent prediction ability in validation datasets. Patients in the low-RiskScore group had a better prognosis, a higher abundance of immune cells (CD4 + T cell, CD4 + naive T cell, class-switched memory B cell, and Treg), and enhanced expression of most immune checkpoint genes. Importantly, patients with low-RiskScore were more cline benefit from immune checkpoint inhibitor treatment (P < 0.05). Our findings underscore the potential of RiskScore system comprising ten m6A/m5C-related lncRNAs as effective biomarkers for predicting survival outcomes, characterizing the immune landscape, and assessing response to immunotherapy in ESCC.

Orexin-A attenuated motion sickness through modulating neural activity in hypothalamus nuclei.

BACKGROUND AND PURPOSE: We evaluated the hypothesis that central orexin application could counteract motion sickness responses through regulating neural activity in target brain areas. EXPERIMENTAL APPROACH: Thec effects of intracerebroventricular (i.c.v.) injection of orexin-A and SB-334867 (OX1 antagonist) on motion sickness-induced anorexia, nausea-like behaviour (conditioned gaping), hypoactivity and hypothermia were investigated in rats subjected to Ferris wheel-like rotation. Orexin-A responsive brain areas were identified using Fos immunolabelling and were verified via motion sickness responses after intranucleus injection of orexin-A, SB-334867 and TCS-OX2-29 (OX2 antagonist). The efficacy of intranasal application of orexin-A versus scopolamine on motion sickness symptoms in cats was also investigated. KEY RESULTS: Orexin-A (i.c.v.) dose-dependently attenuated motion sickness-related behavioural responses and hypothermia. Fos expression was inhibited in the ventral part of the dorsomedial hypothalamus (DMV) and the paraventricular nucleus (PVN), but was enhanced in the ventral part of the premammillary nucleus ventral part (PMV) by orexin-A (20 µg) in rotated animals. Motion sickness responses were differentially inhibited by orexin-A injection into the DMV (anorexia and hypoactivity), the PVN (conditioned gaping) and the PMV (hypothermia). SB-334867 and TCS-OX2-29 (i.c.v. and intranucleus injection) inhibited behavioural and thermal effects of orexin-A. Orexin-A (60 µg·kg-1) and scopolamine inhibited rotation-induced emesis and non-retching/vomiting symptoms, while orexin-A also attenuated anorexia with mild salivation in motion sickness cats. CONCLUSION AND IMPLICATIONS: Orexin-A might relieve motion sickness through acting on OX1 and OX2 receptors in various hypothalamus nuclei. Intranasal orexin-A could be a potential strategy against motion sickness.

Subtle alterations of vestibulomotor functioning in conductive hearing loss.

Introduction: Conductive hearing loss (CHL) attenuates the ability to transmit air conducted sounds to the ear. In humans, severe hearing loss is often accompanied by alterations to other neural systems, such as the vestibular system; however, the inter-relations are not well understood. The overall goal of this study was to assess vestibular-related functioning proxies in a rat CHL model. Methods: Male Sprague-Dawley rats (N=134, 250g, 2months old) were used in a CHL model which produced a >20dB threshold shift induced by tympanic membrane puncture. Auditory brainstem response (ABRs) recordings were used to determine threshold depth at different times before and after CHL. ABR threshold depths were assessed both manually and by an automated ABR machine learning algorithm. Vestibular-related functioning proxy assessment was performed using the rotarod, balance beam, elevator vertical motion (EVM) and Ferris-wheel rotation (FWR) assays. Results: The Pre-CHL (control) threshold depth was 27.92dB±11.58dB compared to the Post-CHL threshold depth of 50.69dB±13.98dB (mean±SD) across the frequencies tested. The automated ABR machine learning algorithm determined the following threshold depths: Pre-CHL=24.3dB, Post-CHL same day=56dB, Post-CHL 7 days=41.16dB, and Post-CHL 1 month=32.5dB across the frequencies assessed (1, 2, 4, 8, 16, and 32kHz). Rotarod assessment of motor function was not significantly different between pre and post-CHL (~1week) rats for time duration (sec) or speed (RPM), albeit the former had a small effect size difference. Balance beam time to transverse was significantly longer for post-CHL rats, likely indicating a change in motor coordination. Further, failure to cross was only noted for CHL rats. The defection count was significantly reduced for CHL rats compared to control rats following FWR, but not EVM. The total distance traveled during open-field examination after EVM was significantly different between control and CHL rats, but not for FWR. The EVM is associated with linear acceleration (acting in the vertical plane: up-down) stimulating the saccule, while the FWR is associated with angular acceleration (centrifugal rotation about a circular axis) stimulating both otolith organs and semicircular canals; therefore, the difference in results could reflect the specific vestibular-organ functional role. Discussion: Less movement (EVM) and increase time to transverse (balance beam) may be associated with anxiety and alterations to defecation patterns (FWR) may result from autonomic disturbances due to the impact of hearing loss. In this regard, vestibulomotor deficits resulting in changes in balance and motion could be attributed to comodulation of auditory and vestibular functioning. Future studies should manipulate vestibular functioning directly in rats with CHL.

Extracranial-Intracranial Bypass and Risk of Stroke and Death in Patients With Symptomatic Artery Occlusion: The CMOSS Randomized Clinical Trial.

Importance: Prior trials of extracranial-intracranial (EC-IC) bypass surgery showed no benefit for stroke prevention in patients with atherosclerotic occlusion of the internal carotid artery (ICA) or middle cerebral artery (MCA), but there have been subsequent improvements in surgical techniques and patient selection. Objective: To evaluate EC-IC bypass surgery in symptomatic patients with atherosclerotic occlusion of the ICA or MCA, using refined patient and operator selection. Design, Setting, and Participants: This was a randomized, open-label, outcome assessor-blinded trial conducted at 13 centers in China. A total of 324 patients with ICA or MCA occlusion with transient ischemic attack or nondisabling ischemic stroke attributed to hemodynamic insufficiency based on computed tomography perfusion imaging were recruited between June 2013 and March 2018 (final follow-up: March 18, 2020). Interventions: EC-IC bypass surgery plus medical therapy (surgical group; n = 161) or medical therapy alone (medical group; n = 163). Medical therapy included antiplatelet therapy and stroke risk factor control. Main Outcomes and Measures: The primary outcome was a composite of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years after randomization. There were 9 secondary outcomes, including any stroke or death within 2 years and fatal stroke within 2 years. Results: Among 330 patients who were enrolled, 324 patients were confirmed eligible (median age, 52.7 years; 257 men [79.3%]) and 309 (95.4%) completed the trial. For the surgical group vs medical group, no significant difference was found for the composite primary outcome (8.6% [13/151] vs 12.3% [19/155]; incidence difference, -3.6% [95% CI, -10.1% to 2.9%]; hazard ratio [HR], 0.71 [95% CI, 0.33-1.54]; P = .39). The 30-day risk of stroke or death was 6.2% (10/161) in the surgical group and 1.8% (3/163) in the medical group, and the risk of ipsilateral ischemic stroke beyond 30 days through 2 years was 2.0% (3/151) and 10.3% (16/155), respectively. Of the 9 prespecified secondary end points, none showed a significant difference including any stroke or death within 2 years (9.9% [15/152] vs 15.3% [24/157]; incidence difference, -5.4% [95% CI, -12.5% to 1.7%]; HR, 0.69 [95% CI, 0.34-1.39]; P = .30) and fatal stroke within 2 years (2.0% [3/150] vs 0% [0/153]; incidence difference, 1.9% [95% CI, -0.2% to 4.0%]; P = .08). Conclusions and Relevance: Among patients with symptomatic ICA or MCA occlusion and hemodynamic insufficiency, the addition of bypass surgery to medical therapy did not significantly change the risk of the composite outcome of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years. Trial Registration: ClinicalTrials.gov Identifier: NCT01758614.

Impact of qualifying artery on the efficacy of stenting plus medical therapy versus medical therapy alone in patients with symptomatic intracranial stenosis: a post-hoc analysis of the CASSISS trial.

BACKGROUND: A recent trial failed to show any benefit of stenting plus medical therapy over medical therapy alone in patients with symptomatic intracranial stenosis. We aimed to examine whether the symptomatic qualifying artery modifies the effect of stenting plus medical therapy. METHODS: This is a post-hoc analysis of the CASSISS trial that included patients with symptomatic intracranial stenosis, randomly assigned to undergo stenting plus medical therapy or medical therapy alone; 358/380 patients were included. Multivariable logistic regression analysis was used with an interaction term to estimate the altered treatment effect by the qualifying artery. The primary outcome was a composite of stroke or death within 30 days or stroke in the qualifying artery territory beyond 30 days through 1 year. The five secondary outcomes included stroke or death related to the qualifying artery territory at 2 and 3 years. RESULTS: No significant treatment allocation-by-stenosis site interaction was observed (Pinteraction=0.435). Compared with medical therapy alone, the adjusted ORs for stenting plus medical therapy were 2.73 (95% CI 0.42 to 17.65) for internal carotid artery stenosis, 1.20 (95% CI 0.29 to 4.99) for M1 stenosis, 0.23 (95% CI 0.02 to 2.31) for vertebral artery stenosis, and 1.33 (95% CI 0.34 to 5.28) for basilar artery stenosis. Of the five secondary outcomes, none showed a significant treatment allocation-by-stenosis site interaction including stroke in the qualifying artery territory at 2 years (Pinteraction=0.659) and 3 years (Pinteraction=0.493). CONCLUSIONS: Among patients with transient ischemic attacks or ischemic stroke due to severe intracranial atherosclerotic stenosis, there was no evidence that the symptomatic qualifying artery could determine the addition of stenting to medical therapy.

New Role of D-Cycloserine: Shorten Adaptation Process and Extend Maintenance Time of Motion Sickness.

INTRODUCTION: The aim of the study was to investigate the role of D-cycloserine (DCS) in the adaptation process and maintenance of motion sickness (MS). METHODS: In experiment 1, 120 SD rats were used to study the promoting effect of DCS on the adaptation process of MS in rats. They were randomly divided into four groups, DCS-rotation (DCS-Rot), DCS-static, saline-rotation (Sal-Rot), and saline-static, and further divided into three subgroups according to the adaptation time (4 days, 7 days, and 10 days) in each group. After being given DCS (0.5 mg/kg) or 0.9% saline, they were rotated or kept static according to the group. Their fecal granules, total distance, and total activity of spontaneous activity were recorded and analyzed. In experiment 2, other 120 rats were used. The experimental grouping and specific experimental method were the same as experiment 1. According to the grouping of the adaptive maintenance duration, the animals of 14 days, 17 days, and 21 days groups were measured on the corresponding date of the changes in the animals' exploratory behavior. RESULTS: In experiment 1, the fecal granules, total distance, and total activity of spontaneous activity of Sal-Rot returned to the control level on 9 days, and the DCS-Rot group returned to the control level on 6 days, indicating that DCS could shorten the adaptation time of MS rats from 9 days to 6 days. In experiment 2, the Sal-Rot could not maintain the adaptive state after 14 days' absence from the seasickness environment. The fecal granules of DCS-Rot increased significantly, and total distance and total activity of spontaneous activity of DCS-Rot decreased significantly from 17 days. These illustrate that DCS can prolong the adaptive maintenance time from within 14 days to 17 days in MS rats. CONCLUSION: 0.5 mg/kg DCS injected intraperitoneally can shorten the MS adaptation process and extend the maintenance time of adaptation of SD rats.

PbrBZR1 interacts with PbrARI2.3 to mediate brassinosteroid-regulated pollen tube growth during self-incompatibility signaling in pear.

S-RNase-mediated self-incompatibility (SI) prevents self-fertilization and promotes outbreeding to ensure genetic diversity in many flowering plants, including pear (Pyrus sp.). Brassinosteroids (BRs) have well-documented functions in cell elongation, but their molecular mechanisms in pollen tube growth, especially in the SI response, remain elusive. Here, exogenously applied brassinolide (BL), an active BR, countered incompatible pollen tube growth inhibition during the SI response in pear. Antisense repression of BRASSINAZOLE-RESISTANT1 (PbrBZR1), a critical component of BR signaling, blocked the positive effect of BL on pollen tube elongation. Further analyses revealed that PbrBZR1 binds to the promoter of EXPANSIN-LIKE A3 (PbrEXLA3) to activate its expression. PbrEXLA3 encodes an expansin that promotes pollen tube elongation in pear. The stability of dephosphorylated PbrBZR1 was substantially reduced in incompatible pollen tubes, where it is targeted by ARIADNE2.3 (PbrARI2.3), an E3 ubiquitin ligase that is strongly expressed in pollen. Our results show that during the SI response, PbrARI2.3 accumulates and negatively regulates pollen tube growth by accelerating the degradation of PbrBZR1 via the 26S proteasome pathway. Together, our results show that an ubiquitin-mediated modification participates in BR signaling in pollen and reveal the molecular mechanism by which BRs regulate S-RNase-based SI.

Elucidation of the GAUT gene family in eight Rosaceae species and function analysis of PbrGAUT22 in pear pollen tube growth.

MAIN CONCLUSION: The phylogenetic relationship and evolutionary history of the GAUT gene family were identified in 8 Rosaseae species. PbrGAUT22 was involved in controlling pollen tube growth by regulating the content of pectins. In plants, galacturonosyltransferases (GAUTs) were involved in homogalacturonan biosynthesis and functioned in maintaining pollen tube cell wall integrity. However, the feature and evolutionary history of the GAUT gene family in Rosaceae species and candidates in pear pollen tube growth remain unclear. Here, we identified 190 GAUT genes in 8 Rosaceae species, including Chinese white pear (Pyrus bretschneideri), European pear (Pyrus communis), apple (Malus × domestica), peach (Prunus persica), Japanese apricot (Prunus mume), sweet cherry (Prunus avium), woodland strawberry (Fragaria vesca) and black raspberry (Rubus occidentalis). Members in GAUT gene family were divided into 4 subfamilies according to the phylogenetic and structural analysis. Whole-genome duplication events and dispersed duplicates drove the expansion of the GAUT gene family. Among 23 pollen-expressed PbrGAUT genes in pear, PbrGAUT22 showed increased expression level during 1-6 h post-cultured pollen tubes. PbrGAUT22 was localized to the cytoplasm and plasma membrane. Knockdown of PbrGAUT22 expression in pollen tubes caused the decrease of pectin content and inhibited pear pollen tubes growth. Taken together, we investigated the identification and evolution of the GAUT gene family in Rosaceae species, and found that PbrGAUT22 played an essential role in the synthesis of pectin and the growth of pear pollen tubes.

Intensive blood pressure control after endovascular thrombectomy for acute ischaemic stroke (ENCHANTED2/MT): a multicentre, open-label, blinded-endpoint, randomised controlled trial.

BACKGROUND: The optimum systolic blood pressure after endovascular thrombectomy for acute ischaemic stroke is uncertain. We aimed to compare the safety and efficacy of blood pressure lowering treatment according to more intensive versus less intensive treatment targets in patients with elevated blood pressure after reperfusion with endovascular treatment. METHODS: We conducted an open-label, blinded-endpoint, randomised controlled trial at 44 tertiary-level hospitals in China. Eligible patients (aged ≥18 years) had persistently elevated systolic blood pressure (≥140 mm Hg for >10 min) following successful reperfusion with endovascular thrombectomy for acute ischaemic stroke from any intracranial large-vessel occlusion. Patients were randomly assigned (1:1, by a central, web-based program with a minimisation algorithm) to more intensive treatment (systolic blood pressure target <120 mm Hg) or less intensive treatment (target 140-180 mm Hg) to be achieved within 1 h and sustained for 72 h. The primary efficacy outcome was functional recovery, assessed according to the distribution in scores on the modified Rankin scale (range 0 [no symptoms] to 6 [death]) at 90 days. Analyses were done according to the modified intention-to-treat principle. Efficacy analyses were performed with proportional odds logistic regression with adjustment for treatment allocation as a fixed effect, site as a random effect, and baseline prognostic factors, and included all randomly assigned patients who provided consent and had available data for the primary outcome. The safety analysis included all randomly assigned patients. The treatment effects were expressed as odds ratios (ORs). This trial is registered at ClinicalTrials.gov, NCT04140110, and the Chinese Clinical Trial Registry, 1900027785; recruitment has stopped at all participating centres. FINDINGS: Between July 20, 2020, and March 7, 2022, 821 patients were randomly assigned. The trial was stopped after review of the outcome data on June 22, 2022, due to persistent efficacy and safety concerns. 407 participants were assigned to the more intensive treatment group and 409 to the less intensive treatment group, of whom 404 patients in the more intensive treatment group and 406 patients in the less intensive treatment group had primary outcome data available. The likelihood of poor functional outcome was greater in the more intensive treatment group than the less intensive treatment group (common OR 1·37 [95% CI 1·07-1·76]). Compared with the less intensive treatment group, the more intensive treatment group had more early neurological deterioration (common OR 1·53 [95% 1·18-1·97]) and major disability at 90 days (OR 2·07 [95% CI 1·47-2·93]) but there were no significant differences in symptomatic intracerebral haemorrhage. There were no significant differences in serious adverse events or mortality between groups. INTERPRETATION: Intensive control of systolic blood pressure to lower than 120 mm Hg should be avoided to prevent compromising the functional recovery of patients who have received endovascular thrombectomy for acute ischaemic stroke due to intracranial large-vessel occlusion. FUNDING: The Shanghai Hospital Development Center; National Health and Medical Research Council of Australia; Medical Research Futures Fund of Australia; China Stroke Prevention; Shanghai Changhai Hospital, Science and Technology Commission of Shanghai Municipality; Takeda China; Hasten Biopharmaceutic; Genesis Medtech; Penumbra.

Effect of Stenting Plus Medical Therapy vs Medical Therapy Alone on Risk of Stroke and Death in Patients With Symptomatic Intracranial Stenosis: The CASSISS Randomized Clinical Trial.

Importance: Prior randomized trials have generally shown harm or no benefit of stenting added to medical therapy for patients with symptomatic severe intracranial atherosclerotic stenosis, but it remains uncertain as to whether refined patient selection and more experienced surgeons might result in improved outcomes. Objective: To compare stenting plus medical therapy vs medical therapy alone in patients with symptomatic severe intracranial atherosclerotic stenosis. Design, Setting, and Participants: Multicenter, open-label, randomized, outcome assessor-blinded trial conducted at 8 centers in China. A total of 380 patients with transient ischemic attack or nondisabling, nonperforator (defined as nonbrainstem or non-basal ganglia end artery) territory ischemic stroke attributed to severe intracranial stenosis (70%-99%) and beyond a duration of 3 weeks from the latest ischemic symptom onset were recruited between March 5, 2014, and November 10, 2016, and followed up for 3 years (final follow-up: November 10, 2019). Interventions: Medical therapy plus stenting (n = 176) or medical therapy alone (n = 182). Medical therapy included dual-antiplatelet therapy for 90 days (single antiplatelet therapy thereafter) and stroke risk factor control. Main Outcomes and Measures: The primary outcome was a composite of stroke or death within 30 days or stroke in the qualifying artery territory beyond 30 days through 1 year. There were 5 secondary outcomes, including stroke in the qualifying artery territory at 2 years and 3 years as well as mortality at 3 years. Results: Among 380 patients who were randomized, 358 were confirmed eligible (mean age, 56.3 years; 263 male [73.5%]) and 343 (95.8%) completed the trial. For the stenting plus medical therapy group vs medical therapy alone, no significant difference was found for the primary outcome of risk of stroke or death (8.0% [14/176] vs 7.2% [13/181]; difference, 0.4% [95% CI, -5.0% to 5.9%]; hazard ratio, 1.10 [95% CI, 0.52-2.35]; P = .82). Of the 5 prespecified secondary end points, none showed a significant difference including stroke in the qualifying artery territory at 2 years (9.9% [17/171] vs 9.0% [16/178]; difference, 0.7% [95% CI, -5.4% to 6.7%]; hazard ratio, 1.10 [95% CI, 0.56-2.16]; P = .80) and 3 years (11.3% [19/168] vs 11.2% [19/170]; difference, -0.2% [95% CI, -7.0% to 6.5%]; hazard ratio, 1.00 [95% CI, 0.53-1.90]; P > .99). Mortality at 3 years was 4.4% (7/160) in the stenting plus medical therapy group vs 1.3% (2/159) in the medical therapy alone group (difference, 3.2% [95% CI, -0.5% to 6.9%]; hazard ratio, 3.75 [95% CI, 0.77-18.13]; P = .08). Conclusions and Relevance: Among patients with transient ischemic attack or ischemic stroke due to symptomatic severe intracranial atherosclerotic stenosis, the addition of percutaneous transluminal angioplasty and stenting to medical therapy, compared with medical therapy alone, resulted in no significant difference in the risk of stroke or death within 30 days or stroke in the qualifying artery territory beyond 30 days through 1 year. The findings do not support the addition of percutaneous transluminal angioplasty and stenting to medical therapy for the treatment of patients with symptomatic severe intracranial atherosclerotic stenosis. Trial Registration: ClinicalTrials.gov Identifier: NCT01763320.

Stroboscopic lighting with intensity synchronized to rotation velocity alleviates motion sickness gastrointestinal symptoms and motor disorders in rats.

Motion sickness (MS) is caused by mismatch between conflicted motion perception produced by motion challenges and expected "internal model" of integrated motion sensory pattern formed under normal condition in the brain. Stroboscopic light could reduce MS nausea symptom via increasing fixation ability for gaze stabilization to reduce visuo-vestibular confliction triggered by distorted vision during locomotion. This study tried to clarify whether MS induced by passive motion could be alleviated by stroboscopic light with emitting rate and intensity synchronized to acceleration-deceleration phase of motion. We observed synchronized and unsynchronized stroboscopic light (SSL: 6 cycle/min; uSSL: 2, 4, and 8 cycle/min) on MS-related gastrointestinal symptoms (conditioned gaping and defecation responses), motor disorders (hypoactivity and balance disturbance), and central Fos protein expression in rats receiving Ferris wheel-like rotation (6 cycle/min). The effects of color temperature and peak light intensity were also examined. We found that SSL (6 cycle/min) significantly reduced rotation-induced conditioned gaping and defecation responses and alleviated rotation-induced decline in spontaneous locomotion activity and disruption in balance beam performance. The efficacy of SSL against MS behavioral responses was affected by peak light intensity but not color temperature. The uSSL (4 and 8 cycle/min) only released defecation but less efficiently than SSL, while uSSL (2 cycle/min) showed no beneficial effect in MS animals. SSL but not uSSL inhibited Fos protein expression in the caudal vestibular nucleus, the nucleus of solitary tract, the parabrachial nucleus, the central nucleus of amygdala, and the paraventricular nucleus of hypothalamus, while uSSL (4 and 8 cycle/min) only decreased Fos expression in the paraventricular nucleus of hypothalamus. These results suggested that stroboscopic light synchronized to motion pattern might alleviate MS gastrointestinal symptoms and motor disorders and inhibit vestibular-autonomic pathways. Our study supports the utilization of motion-synchronous stroboscopic light as a potential countermeasure against MS under abnormal motion condition in future.

Cellulose accumulation mediated by PbrCSLD5, a cellulose synthase-like protein, results in cessation of pollen tube growth in Pyrus bretschneideri.

Cellulose, a key component of the cell wall, plays an important role in maintaining the growth of pollen tubes. However, the molecular mechanism of cellulose participating in the cessation of pear pollen tube growth remains unclear. Here, we reported that at 15 h post-cultured (HPC), the slow-growth pear pollen tubes showed thickened cell walls and cellulose accumulation in the inner wall. Transcriptome data and quantitative real-time PCR analysis showed that PbrCSLD5, a cellulose synthesis-like gene, was highly expressed in the 15 HPC pear pollen tubes. Knockdown of PbrCSLD5 caused a decrease in cellulose content in pear pollen tubes. Moreover, PbrCSLD5 overexpression in Arabidopsis resulted in the accumulation of cellulose and disruption of normal pollen tube growth. Transcription factor PbrMADS52 was found to bind to the promoter of PbrCSLD5 and enhanced its expression. Our results suggested that the PbrMADS52-PbrCSLD5 signaling pathway led to increased cellulose content in the pear pollen tube cell wall, thereby inhibiting pollen tube growth. These results provided new insights into the regulation of pollen tube growth.

Global simulation of fine resolution land use/cover change and estimation of aboveground biomass carbon under the shared socioeconomic pathways.

Land use change driven by human activities plays a critical role in the terrestrial carbon budget through habitat loss and vegetation change. Despite the projections of the global population and economic growth under the framework of the Shared Socioeconomic Pathways (SSPs), little is known of land use/cover change (LUCC) at a fine spatial resolution and how carbon pools respond to LUCC under different SSPs. This study projected the future global LUCC with 1 km spatial resolution and a 10-year time step from 2010 to 2100 and then explored its direct impacts on aboveground biomass carbon (AGB) under SSPs. Scenario SSP3 yields the highest global cropland expansion, among which approximately 48% and 46% is expected to be located in the current forest land and grassland, respectively. Scenario SSP1 has the largest forest expansion and is mainly converted from grassland (54%) and cropland (30%). Due to the spatial change in land use/cover, global AGB loss is expected to reach approximately 3.422 Pg C in 2100 under scenario SSP3 and increases by approximately 0.587 Pg C under scenario SSP1. Africa is expected to lose 30% of AGB under the scenario SSP3. Aboveground biomass in Asia will fix 0.774 Pg C to reverse the AGB loss in 2100 under scenario SSP1. The global carbon loss estimated by the land use products with 10 km and 25 km resolution are less than that with 1 km by 1.5% (ranging from -11.2% in Africa to +34.0% in Oceania) and 2.9% (ranging from -11.8% in Africa to +24.0% in Oceania), respectively. These findings suggest that sufficient spatial details in the existing SSP scenario projections could reduce the uncertainties of AGB assessment, and reasonable land use development and management is a key measure to mitigate the negative impacts of LUCC on the biomass carbon pool.

Safety of endovascular therapy for symptomatic intracranial artery stenosis: a national prospective registry.

INTRODUCTION: The safety outcomes of endovascular therapy for intracranial artery stenosis in a real-world stetting are largely unknown. The Clinical Registration Trial of Intracranial Stenting for Patients with Symptomatic Intracranial Artery Stenosis (CRTICAS) was a prospective, multicentre, real-world registry designed to assess these outcomes and the impact of centre experience. METHODS: 1140 severe, symptomatic intracranial arterial stenosis (ICAS) patients treated with endovascular therapy were included from 26 centres, further divided into three groups according to the annual centre volume of intracranial angioplasty and stent placement procedures over 2 years: (1) high volume for ≥25 cases/year; (2) moderate volume for 10-25 cases/year and (3) low volume for <10 cases/year. RESULTS: The rate of 30-day stroke, transient ischaemic attack or death was 9.7% (111), with 5.4%, 21.1% and 9.7% in high-volume, moderate-volume and low-volume centres, respectively (p<0.05). Multivariable logistic regression confirmed high-volume centres had a significantly lower primary endpoint compared with moderate-volume centres (OR=0.187, 95% CI: 0.056 to 0.627; p≤0.0001), while moderate-volume and low-volume centres showed no significant difference (p=0.8456). CONCLUSION: Compared with the preceding randomised controlled trials, this real-world, prospective, multicentre registry shows a lower complication rate of endovascular treatment for symptomatic ICAS. Non-uniform utilisation in endovascular technology, institutional experience and patient selection in different volumes of centres may have an impact on overall safety of this treatment.

Efficacy and Safety of a Novel Thrombectomy Device in Patients With Acute Ischemic Stroke: A Randomized Controlled Trial.

Purpose: The Tonbridge stent is a novel retriever with several design improvements which aim to achieve promising flow reperfusion in the treatment of acute ischemic stroke (AIS). We conducted a randomized controlled, multicenter, non-inferiority trial to compare the safety and efficacy of the Tonbridge stent with the Solitaire FR. Methods: AIS patients aged 18-85 years with large vessel occlusion in anterior circulation who could undergo puncture within 6 h of symptom onset were included. Randomization was performed on a 1:1 ratio to thrombectomy with either the Tonbridge stent or the Solitaire FR. The primary efficacy endpoint was successful reperfusion using a modified thrombolysis in cerebral infarction score (mTICI) of 2b/3. Safety outcomes were symptomatic intracranial hemorrhage (sICH) within 24 ± 6 h and all-cause mortality within 90 days. A clinically relevant non-inferiority margin of 12% was chosen as the acceptable difference between groups. Secondary endpoints included time from groin puncture to reperfusion, National Institutes of Health Stroke Scale (NIHSS) score at 24 h and at 7 days, and a modified Rankin Scale (mRS) score of 0-2 at 90 days. Results: A total of 220 patients were enrolled; 104 patients underwent thrombectomy with the Tonbridge stent and 104 were treated with the Solitaire FR. In all test group patients, the Tonbridge was used as a single retriever without rescuing by other thrombectomy devices. Angioplasty with balloon and/or stent was performed in 26 patients in the Tonbridge group and 16 patients in the Solitaire group (p = 0.084). Before angioplasty, 86.5% of those in the Tonbridge group and 81.7% of those in the Solitaire group reached successful reperfusion (p = 0.343). Finally, more patients in the Tonbridge group achieved successful reperfusion (92.3 vs. 84.6%, 95% CI of difference value 0.9-16.7%, p < 0.0001). There were no significant differences on sICH within 24 ± 6 h between the two groups. All-cause mortality within 90 days was 13.5% in the Tonbridge group and 16.3% in the Solitaire group (p = 0.559). We noted no significant differences between groups on the NIHSS at either 24 h or 7 days and the mRS of 0-2 at 90 days. Conclusion: The trial indicated that the Tonbridge stent was non-inferior to the Solitaire FR within 6 h of symptom onset in cases of large vessel occlusion stroke. Clinical Trial Registration:ClinicalTrials.gov, number: NCT03210623.

Sea Voyage Training and Motion Sickness Effects on Working Ability and Life Quality After Landing.

BACKGROUND: The effects of seasickness on working performance during motion exposure have been reported, while the aftereffects on working ability and life quality decline (WLD) still remain unclarified.METHODS: Two cohorts of healthy male Chinese subjects received either a single (SSV) or repeated (RSV) sea voyage training program on different vessels. A seasickness incidence (SSI) questionnaire was administered to assess the prevalence of seasickness symptoms (vomiting, nausea, other, or no symptoms). A WLD questionnaire was used to survey the general feeling of WLD (severe, moderate, slight, and none) by a 4-point score as well as the incidence rate (IR) of specific WLD items within 24 h after landing.RESULTS: The RSV cohort had lower overall IR of WLD than the SSV cohort (54.64% vs. 63.78%, N 657 for both cohorts). The landing ship trainees in both cohorts showed higher general WLD score and higher IRs of physical fatigue, sleep disorder, and spontaneous locomotion decrement than those trained on the small vessels. Subjects with vomiting or nausea had higher general WLD score and higher IRs of concentration distraction, physical fatigue, anorexia, and spontaneous locomotion decrement than those with no symptoms. Higher IRs of firing accuracy decline (SSV: 21.35% vs. 7.13%, 9.14%; RSV: 22.11% vs. 9.28%, 5.27%), equipment operation disturbance (SSV: 16.85% vs. 3.57%, 6.85%; RSV: 20.47% vs. 7.85%, 7.03%) were also observed in the vomiting subjects than those with other symptoms and no symptoms.DISCUSSION: Significant WLD after landing was associated with transportation types, seasickness severity, and habituation during sea voyage training.Qi R-R, Xiao S-F, Su Y, Mao Y-Q, Pan L-L, Li C-H, Lu Y-L, Wang J-Q, Cai Y-L. Sea voyage training and motion sickness effects on working ability and life quality after landing. Aerosp Med Hum Perform. 2021; 92(2):9298.

Identifying early gastric cancer under magnifying narrow-band images with deep learning: a multicenter study.

BACKGROUND AND AIMS: Narrow-band imaging with magnifying endoscopy (ME-NBI) has shown advantages in the diagnosis of early gastric cancer (EGC). However, proficiency in diagnostic algorithms requires substantial expertise and experience. In this study, we aimed to develop a computer-aided diagnostic model for EGM (EGCM) to analyze and assist in the diagnosis of EGC under ME-NBI. METHODS: A total of 1777 ME-NBI images from 295 cases were collected from 3 centers. These cases were randomly divided into a training cohort (n = 170), an internal test cohort (ITC, n = 73), and an external test cohort (ETC, n = 52). EGCM based on VGG-19 architecture (Visual Geometry Group [VGG], Oxford University, Oxford, UK) with a single fully connected 2-classification layer was developed through fine-tuning and validated on all cohorts. Furthermore, we compared the model with 8 endoscopists with varying experience. Primary comparison measures included accuracy, area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: EGCM acquired AUCs of .808 in the ITC and .813 in the ETC. Moreover, EGCM achieved similar predictive performance as the senior endoscopists (accuracy: .770 vs .755, P = .355; sensitivity: .792 vs .767, P = .183; specificity: .745 vs .742, P = .931) but better than the junior endoscopists (accuracy: .770 vs .728, P < .05). After referring to the results of EGCM, the average diagnostic ability of the endoscopists was significantly improved in terms of accuracy, sensitivity, PPV, and NPV (P < .05). CONCLUSIONS: EGCM exhibited comparable performance with senior endoscopists in the diagnosis of EGC and showed the potential value in aiding and improving the diagnosis of EGC by endoscopists.

Profiling of cybersickness and balance disturbance induced by virtual ship motion immersion combined with galvanic vestibular stimulation.

Profile of cybersickness and balance disturbance induced by virtual ship motion alone and in combination with galvanic vestibular stimulation (GVS) remained unclear. Subjects were exposed to a ship deck vision scene under simulated Degree 5 or 3 sea condition using a head-mounted virtual reality display with or without GVS. Virtual ship motion at Degree 5 induced significant cybersickness with symptom profile: nausea syndrome > central (headache and dizziness) > peripheral (cold sweating) > increased salivation. During a single session of virtual ship motion exposure, GVS aggravated balance disturbance but did not affect most cybersickness symptoms except cold sweating. Repeated exposure induced cybersickness habituation which was delayed by GVS, while the temporal change of balance disturbance was unaffected. These results suggested that vestibular inputs play different roles in cybersickness and balance disturbance during virtual reality exposure. GVS might not serve as a potential countermeasure against cybersickness induced by virtual ship motion.

Treatment with Minocycline Suppresses Microglia Activation and Reverses Neural Stem Cells Loss after Simulated Microgravity.

The present study aimed to investigate the effect of microglia on simulated microgravity-induced hippocampal neurogenesis reduction and the possible mechanism underlying. Adult rats were treated with tail suspension for different times and the changes of neural stem cells (NSCs) were examined by immunohistochemistry. Then, minocycline was used to inhibit the activation of microglia, and the numbers of microglia and NSCs were detected after microgravity. Additionally, liquid protein chip analysis was applied to detect proinflammatory factors in hippocampus in order to find out the cytokines responsible for microglia activation after microgravity. The results revealed that microgravity increased the numbers of Iba1+ cells and decreased the numbers of BrdU+ and DCX+ cells in hippocampus but did not affect the ratio of NeuN+/BrdU+ cells to the total number of BrdU+ cells. After treated with minocycline, activated microglia were suppressed and the reduction of NSCs induced by microgravity recovered. Besides, compared with the control, higher concentrations of INF-γ and TNF-α were detected in the rats treated with microgravity. Our study provides the first evidence that microglia-mediated inflammation plays an important part in microgravity-induced neurogenesis reduction in hippocampus, and INF-γ and TNF-α secreted by microglia might be the key factors in this process.

Assessing the Autonomic and Behavioral Effects of Passive Motion in Rats using Elevator Vertical Motion and Ferris-Wheel Rotation.

The overall goal of this study is to assess the autonomic and behavioral effects of passive motion in rodents using the elevator vertical motion and Ferris-wheel rotation devices. These assays can help confirm the integrity and normal functioning of the autonomic nervous system. They are coupled to quantitative measures based on defecation counting, open-field examination, and balance beam crossing. The advantages of these assays are their simplicity, reproducibility, and quantitative behavioral measures. The limitations of these assays are that the autonomic reactions could be epiphenomena of non-vestibular disorders and that a functioning vestibular system is required. Examination of disorders such as motion sickness will be greatly aided by the detailed procedures of these assays.