Long non-coding RNA MALAT1 regulates cell proliferation and apoptosis via miR-135b-5p/GPNMB axis in Parkinson's disease cell model.

BACKGROUNDS: Parkinson's disease (PD) is a common age-related neurodegenerative disorder worldwide. This research aimed to investigate the effects and mechanism underlying long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in PD. METHODS: SK-N-SH and SK-N-BE cells were treated with MPP+ to establish the MPP+-stimulated cell model of PD, and MALAT1 expression was determined. Then, the effects of MALAT1 depletion on cell proliferation and apoptosis were determined in the MPP+-stimulated cell model of PD. Besides, the correlations between microRNA-135b-5p (miR-135b-5p) and MALAT1 or glycoprotein nonmetastatic melanoma protein B (GPNMB) in MPP+-stimulated cell model of PD were explored. RESULTS: MALAT1 was increasingly expressed and downregulation of MALAT1 promoted cell proliferation while inhibited apoptosis in MPP+-stimulated cells. Besides, miR-135b-5p was a target of MALAT1 and directly targeted to GPNMB. Further investigation indicated that suppression of MALAT1 regulated cell proliferation and apoptosis by miR-135b-5p/GPNMB axis. CONCLUSION: Our findings reveal that MALAT1/miR-135b-5p/GPNMB axis regulated cell proliferation and apoptosis in MPP+-stimulated cell model of PD, providing a potential biomarker and therapeutic target for PD.

Simulation Study on Temperature Control Performance of Lithium-Ion Battery Fires by Fine Water Mist in Energy Storage Stations.

The combustion of lithium-ion batteries is characterized by fast ignition, prolonged duration, high combustion temperature, release of significant energy, and generation of a large number of toxic gases. Fine water mist has characteristics such as a high fire extinguishing efficiency and environmental friendliness. In order to thoroughly investigate the temperature control effect of fine water mist on lithium-ion battery fires. This study employs numerical simulation methods, utilizing PyroSim software to simulate the fire process in lithium-ion battery energy storage compartments. First, we focus on the variation patterns of flame, changes in combustion temperature, and heat release rate over time at environmental temperatures of 10, 25, and 35 °C. Subsequently, the suppression of flame, reduction in temperature, and changes in heat release rate are simulated for water mist in lithium-ion battery fires. The simulation results indicate that the environmental temperature has a considerable impact on the flame but a lesser effect on the heat release rate. Fine water mist effectively impedes the spread of thermal runaway between internal battery core cells, leading to a reduction in the flame size and a significant decrease in the maximum temperature and heat release rate. The numerical simulation results can provide scientific guidance for the prevention and control of fires in lithium-ion battery energy storage compartments.

Targeting C21orf58 is a Novel Treatment Strategy of Hepatocellular Carcinoma by Disrupting the Formation of JAK2/C21orf58/STAT3 Complex.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Functionally uncharacterized genes are an attractive repository to explore candidate oncogenes. It is demonstrated that C21orf58 displays an oncogenic role in promoting cell growth, tumorigenesis and sorafenib resistance of HCC cells by abnormal activation of STAT3 signaling. Mechanistically, a novel manner to regulate STAT3 signaling that adaptor C21orf58 forms a ternary complex is reveal with N-terminal domain of STAT3 and SH2 domain of JAK2, by which C21orf58 overactivates wild-type STAT3 by facilitating its phosphorylation mediated by JAK2, and hyper-activates of constitutively mutated STAT3 due to preferred binding with C21orf58 and JAK2. Moreover, it is validated that inhibition of C21orf58 with drug alminoprofen, selected by virtual screening, could effectively repress the viability and tumorigenesis of HCC cells. Therefore, it is identified that C21orf58 functions as an oncogenic adaptor, reveal a novel regulatory mechanism of JAK2/STAT3 signaling, explain the cause of abnormal activity of activated mutants of STAT3, and explore the attractive therapeutic potential by targeting C21orf58 in HCC.

Endovascular Therapy for Basilar Artery Occlusion in Sudden Onset to Maximal Deficit Ischemic Events.

BACKGROUND: The presence of sudden onset to maximal deficit (SOTMD) in patients with acute basilar artery occlusion often results in more severe outcomes. However, the effect of endovascular therapy on SOTMD and whether the outcome is affected by onset-to-puncture time remain unclear. METHODS AND RESULTS: This retrospective analysis was conducted using data from the prospective BASILAR (Endovascular Treatment for Acute Basilar Artery Occlusion Study Registry). Consecutive patients with basilar artery occlusion receiving endovascular therapy were dichotomized into SOTMD and non-SOTMD cohorts. The primary outcomes included a favorable outcome (modified Rankin scale 0-3), recanalization, and mortality at 90 days. The outcomes of patients with SOTMD were analyzed using multivariable logistic regression. In the multivariate analysis, a favorable outcome was similar between the two cohorts (odds ratio [OR], 0.88 [95% CI, 0.58-1.34]; P=0.5), although the mortality of patients with SOTMD was higher than that of patients with non-SOTMD (OR, 1.67 [95% CI, 1.14-2.44]; P=0.008). The probability of mortality increased from 40.0% at 1 hour to 70.0% at 6 hours in the SOTMD cohort, and favorable outcomes of patients with non-SOTMD declined from 38.0% at 1 hour to 18.0% at 8 hours. CONCLUSIONS: No significant difference was observed in favorable outcomes between the SOTMD and non-SOTMD groups, although mortality was higher in the SOTMD cohort. The patients with SOTMD had a stronger time dependence for endovascular therapy in terms of mortality, while the time dependency regarding favorable outcome in the NSOTMD group was even higher. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1800014759.

Prominent Vessel Signs After Endovascular Thrombectomy Corelates with Unexplained Neurological Deterioration and is a More Reliable Imaging Predictor of Prognosis in Anterior Large Vessel Occlusion Stroke.

OBJECTIVE: Fifty percent of patients who undergo endovascular thrombectomy (EVT) for large-vessel occlusion exhibit unfavorable outcomes. The primary factor is attributed to persistent brain impairment even after successful EVT. The prominent vessel sign (PVS) on magnetic resonance susceptibility-weighted imaging reflects the territory of dysmetabolism and may facilitate an expeditious assessment for prognostication. We aimed to examine the relationship between PVS after EVT and the occurrence of early neurological deterioration (END) and 3-month outcomes. METHODS: Patients who underwent EVT and multimodal magnetic resonance imaging were included. END was defined as an increase of ≥2 in the National Institutes of Health Stroke Scale within 72 hours after EVT. Symptomatic intracranial hemorrhage, malignant edema, and surgical complications were defined as definite END, whereas the other symptoms were categorized as unexplained END (ux-END). The PVS-Alberta Stroke Program Early CT Score (ASPECTS) score was used to evaluate the asymmetric cerebral venous signal on the susceptibility-weighted imaging sequences semiquantitatively. RESULTS: A total of 116 eligible patients were included, 18 (15.5%) of whom presented with ux-END. The 72 hour National Institutes of Health Stroke Scale was strongly correlated with diffusion-weighted imaging infarct volume and PVS-ASPECTS and was significantly higher in the ux-END group (16 ± 6 vs. 5 ± 4, P = 0.001). The PVS-ASPECTS score was significantly associated with poor outcomes (odds ratio 2.551, 95% confidence interval (CI) 1.722-3.780, P＜0.001), and PVS-ASPECTS (area under the curve 0.884, 95% CI 0.815-0.953, P < 0.001) was superior to diffusion-weighted imaging infarct volume (area under the cure 0.720, 95% CI 0.620-0.820, P = 0.001) in predicting 3-month poor outcome. At the optimal cut-off of 2, the PVS-ASPECT predicted poor outcomes with a sensitivity of 89.7% and a specificity of 78.2%. CONCLUSIONS: PVS 72 hours after EVT correlated with ux-END. The PVS-ASPECTS is a more reliable predictor of stroke prognosis and provides valuable information regarding post-EVT management.

First-pass effect in patients with acute basilar artery occlusions undergoing stent retriever thrombectomy.

OBJECTIVE: First-pass effect (FPE), defined as successful reperfusion (modified Thrombolysis in Cerebral Infarction score 2b-3) with a single stent retriever attempt without salvage treatment, has not been fully identified in patients with acute basilar artery occlusion (BAO). The authors' aim was to assess the impact of FPE on efficacy and safety for patients with BAO. METHODS: The authors included data from the Acute Basilar Artery Occlusion Study (BASILAR) about patients who underwent mechanical thrombectomy within 24 hours after symptom onset and compared the clinical outcomes of patients who achieved FPE with those who did not. In addition, the authors further compared outcomes between patients with FPE and those with final successful reperfusion achieved with salvage treatment. The primary clinical outcome was favorable outcome (modified Rankin Scale score ≤ 3). RESULTS: Among 471 enrolled patients, FPE was achieved in 83 (17.6%) who underwent acute BAO thrombectomy. FPE was strongly associated with favorable outcome (adjusted OR 2.84, 95% CI 1.56-5.16, p = 0.001), lower rate of mortality (28.9% of FPE patients vs 48.2% of non-FPE patients, p = 0.001), and shorter median time from groin puncture to recanalization (65 minutes vs 110 minutes, p < 0.001). Occlusion site of the distal basilar artery, cardioembolism, and undetermined etiology were positive predictors of FPE, whereas baseline National Institutes of Health Stroke Scale score was a negative predictor. Compared with final successful reperfusion, FPE also contributed independently to favorable outcomes (adjusted OR 2.25, 95% CI 1.23-4.10, p = 0.008). CONCLUSIONS: FPE was associated with 90-day favorable outcome in patients with acute BAO who underwent stent retriever thrombectomy within 24 hours. Clinical trial registration no.: ChiCTR1800014759 (www.chictr.org.cn).

Numerical Simulation of Fire in Underground Commercial Street.

In this study, while aiming at the prevention of fire accidents in underground commercial streets, an underground commercial street is selected as a research object, and the building fire is numerically simulated using the PyroSim software. Fire simulation scenarios are divided according to different fire zones by analyzing the temperature, carbon monoxide (CO) concentration, and visibility in the smoke layer inside a building. The available safe evacuation time is calculated according to the critical fire hazard judgment conditions. We found that the time when the flue gas temperature and CO concentration reached the critical value in the fire site was longer than the time when the visibility reached the critical value reducing or even avoiding the spread of smoke from the fire area to the evacuation stairs can provide effective help for crowd evacuation. Finally, the safety of the building is evaluated, and fire prevention countermeasures are defined based on the actual situation and fire numerical simulation results to reduce fire incidence, casualties, and economic losses.

Neutrophil-to-lymphocyte ratio predicts parenchymal hematoma after mechanical thrombectomy in basilar artery occlusion.

Background: parenchymal hematoma (PH) is a severe complication of endovascular treatment (EVT) for acute basilar artery occlusion (ABAO). This study aimed to evaluate the incidence and predictors of PH after EVT for ABAO. Methods: Using data from the Endovascular Treatment for Acute Basilar Artery Occlusion Study, we enrolled patients treated with mechanical thrombectomy from the BASILAR registry. PH was assessed in accordance with the Heidelberg Bleeding Classification. Logistic regression was used to identify predictors of PH. Results: A total of 639 patients were included. Forty-eight patients (7.5%) were diagnosed with PH within 48 h of EVT. Ninety-day mortality was higher in patients with PH compared with those without (81.3 vs. 42.8%, P < 0.001). Favorable neurological outcomes (modified Rankin scale score, 0-3) rates was lower in patients with PH compared with those without (6.3 vs. 34.5%, P < 0.001). With a multivariate analysis, hypertension [odds ratio (OR) = 2.30, 95% confidence interval (CI) 1.04-5.08], pre-treatment National Institutes of Health Stroke Score (NIHSS, >25; OR = 3.04, 95% CI 1.43-6.45), and Neutrophil-to-lymphocyte ratio (NLR, >10; OR = 1.88, 95% CI 1.02-3.48) were associated with PH after EVT. Conclusions: PH occurred at a rate of 7.5% after EVT in patients with ABAO. Hypertension, higher baseline NIHSS, and higher NLR value increase the risk of PH after EVT for ABAO.

Hyperdense Artery Sign and Clinical Outcomes After Endovascular Treatment in Acute Basilar Artery Occlusion.

Background: This study aimed to investigate the association between the hyperdense basilar artery sign (HBAS) on non-enhanced computed tomography (CT) and clinical outcomes in patients with acute basilar artery occlusion (BAO) who underwent endovascular treatment (EVT). Methods: Eligible patients who underwent EVT due to acute BAO between January 2014 and May 2019 were divided into two groups based on HBAS. HBAS was assessed by two neuroradiologists using five grades on nonenhanced CT. The primary outcome was a favorable functional outcome (defined as a modified Rankin Scale [mRS] of 0-3) at 90 days. Secondary outcomes included successful recanalization and mortality within 90 days. Results: Among 829 patients with BAO as assessed with CT angiography, magnetic resonance angiography, or digital subtraction angiography, 643 patients were treated with EVT. Of these, 51.32% (330/643) had HBAS. Patients with HBAS were older and had more severe neurological deficits and a higher frequency of atrial fibrillation than those without HBAS. There was no significant difference in favorable outcome (adjusted odds ratio [aOR]: 1.354, 95% confidence interval [CI]: 0.906-2.024; p = 0.14), successful recanalization (aOR: 0.926, 95% CI: 0.616--1.393; p = 0.71), and mortality (aOR: 1.193, 95% CI: 0.839-1.695; p = 0.33) between patients with or without HBAS. Subgroup analysis showed that the HBAS predicted a favorable outcome in patients aged <60 years (aOR: 2.574, 95% CI: 1.234-5.368; p = 0.01) and patients with vertebral artery-V4 segment occlusion (aOR: 3.738, 95% CI: 1.212-11.530; p = 0.02). In patients with HBAS, the baseline National Institutes of Health Stroke Scale (NIHSS) score, posterior circulation-Acute Stroke Prognosis Early Computed Tomography Score (pc-ASPECTS), and stent retriever were associated with successful recanalization. Conclusions: Our study did not find a significant association between HBAS and favorable outcomes and successful recanalization in patients with BAO who underwent EVT. Moreover, large prospective studies are warranted to further investigate this relationship.

Long non-coding RNA MALAT1 regulates cell proliferation and apoptosis via miR-135b-5p/GPNMB axis in Parkinson's disease cell model

BACKGROUNDS: Parkinson's disease (PD) is a common age-related neurodegenerative disorder worldwide. This research aimed to investigate the effects and mechanism underlying long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in PD. METHODS: SK-N-SH and SK-N-BE cells were treated with MPP+ to establish the MPP+-stimulated cell model of PD, and MALAT1 expression was determined. Then, the effects of MALAT1 depletion on cell proliferation and apoptosis were determined in the MPP+-stimulated cell model of PD. Besides, the correlations between microRNA-135b-5p (miR-135b-5p) and MALAT1 or glycoprotein nonmetastatic melanoma protein B (GPNMB) in MPP+-stimulated cell model of PD were explored. RESULTS: MALAT1 was increasingly expressed and downregulation of MALAT1 promoted cell proliferation while inhibited apoptosis in MPP+-stimulated cells. Besides, miR-135b-5p was a target of MALAT1 and directly targeted to GPNMB. Further investigation indicated that suppression of MALAT1 regulated cell proliferation and apoptosis by miR-135b-5p/GPNMB axis. CONCLUSION: Our findings reveal that MALAT1/miR-135b-5p/GPNMB axis regulated cell proliferation and apoptosis in MPP+-stimulated cell model of PD, providing a potential biomarker and therapeutic target for PD.

Anti-thyroid antibodies and cerebrospinal fluid findings in neuromyelitis optica spectrum disorders.

OBJECTIVE: To determine the differences of thyroid diseases and ATAbs in multiple sclerosis (MS) and NMOSDs, and to assess the independent impact factors of longitudinally extensive transverse myelitis (LETM) in NMOSDs. RESULTS: Anti-thyroid peroxidase antibodies-positive (TPOAb(+)) and anti-thyroglobulin antibodies-positive (TGAb(+)) were most frequent in NMOSDs. LETM and lesions ≥6 vertebral segments were more frequent in TPOAb(+) NMOSDs than in TPOAb-negative (TPOAb(-)) NMOSDs. TGAb(+) NMOSDs with LETM were significantly more frequent than TGAb-negative (TGAb(-)) NMOSDs. TPOAb(+) and cerebrospinal fluid (CSF) abnormalities were independently associated with LETM. CONCLUSIONS: Our findings demonstrate that ATAbs and thyroid diseases are significantly different in MS and NMOSD patients and CSs. TPOAb(+) and CSF abnormalities may be possible predictors of the severity of spinal cord lesions.

Clinical and laboratory factors in the differential diagnosis of tuberculous and cryptococcal meningitis in adult HIV-negative patients.

Objective It is difficult to make the differential diagnosis between tuberculous meningitis (TBM) and cryptococcal meningitis (CM) when the smear is negative. The objective of this study was to create a diagnostic rule for differentiating TBM from CM in adult HIV-negative patients based on clinical and laboratory features. Methods The clinical and laboratory data of 219 adult HIV-negative patients satisfying the diagnostic criteria for tuberculous (n=100) and cryptococcal (n=119) meningitis hospitalized at the Third Affiliated Hospital of Sun Yat-Sen University during the period 2000-2009 were retrospectively analyzed. Features found to be independently predictive of tuberculous meningitis were modeled using a multivariate logistic regression to create a diagnostic rule. The performance of the diagnostic rule was assessed using a prospective test data method. Results Six factors were found to be predictive of a diagnosis of tuberculous meningitis: gender, mental disorders, vision and/or hearing damage, proteins in the cerebrospinal fluid, the total cerebrospinal fluid white cell count and the coexistence of tuberculosis in peripheral organs. The diagnostic rule developed using these features exhibited 78.0% sensitivity, 95.2% specificity, 92.9% positive predictive value and 84.4% negative predictive value. The corresponding values for the diagnostic rule were 70.0% and 88.0% using prospective test data. Conclusion Clinical and laboratory features can be helpful in the differential diagnosis of tuberculous meningitis and cryptococcal meningitis in adult HIV-negative patients.

Characteristic linear lesions and longitudinally extensive spinal cord lesions in Chinese patients with neuromyelitis optica.

OBJECTIVE: To investigate the characteristics of the linear lesions and longitudinally extensive spinal cord (LESC) lesions in Chinese patients with neuromyelitis optica (NMO). METHODS: The medical records and magnetic resonance imaging (MRI) scans of 29 patients with NMO were reviewed. The frequencies and distributions of linear and LESC lesions were compared against those displayed by 22 multiple sclerosis (MS) patients. Furthermore, the association of lesions with aquaporin-4 IgG (AQP4-IgG) antibody was investigated. RESULTS: The NMO patients had significantly more linear lesions than MS patients (48.3 vs 0%, p<0.001). In the NMO group, linear lesions were found in the medulla in 34.5% (10/29) of patients, across the medullospinal region in 10.3% (3/29) and in the spinal cord in 13.8% (4/29). LESC lesions can be seen more frequently in NMO than MS (72.4 vs 22.7%, p<0.001). In 93.1% (27/29) of the NMO cases, the axial section of the spinal MRI showed lesions on the central gray matter only, whilst the spinal lesions in MS were usually located in the peripheral white matter (72.7%, 16/22). The AQP4-IgG antibody was found to be associated with both linear and LESC lesions in NMO cases. CONCLUSIONS: High frequency of linear lesions and LESC lesions were found in Chinese patients with NMO and linear lesions were correlated with AQP4-IgG antibody.