Human umbilical cord mesenchymal stem cells-derived exosomal circDLGAP4 promotes angiogenesis after cerebral ischemia-reperfusion injury by regulating miR-320/KLF5 axis.

Accumulating evidence suggests that human umbilical cord mesenchymal stem cell-derived exosomes (hUC-MSCs-Exos) are a promising therapeutic strategy for cerebral ischemia-reperfusion injury (CIRI). However, the underlying mechanism remains unclear. hUC-MSCs-Exos were identified by electron microscopy, NTA, and Western blotting. In the hypoxia/reoxygenation (H/R) cell model, human brain microvascular endothelial cells (HBMECs) were cocultured with hUC-MSCs-Exos. Then, cell viability, migration, apoptosis, and tube formation were measured by MTT, flow cytometry, transwell, and tube formation assays. RT-qPCR and Western blotting were used to detect the changes in RNA and protein. RNA pull-down and dual luciferase reporter assays confirmed the relationship between circDLGAP4, miR-320, and KLF5. Ischemia-reperfusion (I/R) rat model was established for in vivo experiments. hUC-MSCs-Exos increased the expression levels of circDLGAP4 and KLF5 but decreased miR-320 in H/R-treated HBMECs by transferring exosomal circDLGAP4. Knockdown of circDLGAP4 in hUC-MSCs-Exos reversed the promoting effects of hUC-MSCs-Exos on cell viability, migration, and tube formation in H/R-treated HBMECs in vitro and also abolished the protective effects of hUC-MSCs-Exos on cerebrovascular injury in I/R rats. Mechanistically, exosomal circDLGAP4 negatively regulated miR-320 in HBMECs, which directly bound to KLF5. In addition, the downregulation of miR-320 could reverse the regulatory effect of exosomal shcircDLGAL5 in H/R-treated HBMECs by upregulating KLF5. hUC-MSCs-Exos-derived circDLGAP4 reduced cerebrovascular injury by regulating miR-320/KLF5 signaling. These results provide a stem cell-based approach to treat CIRI.

Exosomal circBBS2 inhibits ferroptosis by targeting miR-494 to activate SLC7A11 signaling in ischemic stroke.

Umbilical cord-mesenchymal stem cells (UC-MSCs)-derived exosomes have been considered as an effective treatment for ischemic stroke. CircRNA BBS2 (circBBS2) was demonstrated to be down-regulated in patients with ischemic stroke. However, the role of UC-MSCs-derived exosomal circBBS2 in ischemic stroke and potential mechanisms remain unclear. Hypoxia/reperfusion (H/R)-exposed SH-SY5Y cells and middle cerebral artery occlusion (MCAO)-treated rats were served as in vitro and in vivo models of ischemic stroke. Target gene expression was detected by qRT-PCR. Cell viability was assessed by MTT assay. Ferroptosis was determined by iron, MDA, GSH, and lipid ROS levels. Protein levels were measured by Western blotting. The target relationships among circBBS2, miR-494, and SLC7A11 were validated by RNA-pull down, RIP, and dual-luciferase reporter assays. TTC and HE staining were performed to evaluate cerebral infarction volume and neuropathological changes. circBBS2 was lowly expressed and ferroptosis was triggered in MCAO rats and H/R-stimulated SH-SY5Y cells. UC-MSCs-derived exosomes enhanced cell viability and restrained ferroptosis via increasing circBBS2 expression in SH-SY5Y cells. Mechanistically, circBBS2 sponged miR-494 to enhance the SLC7A11 level. Knockdown of miR-494 or SLC7A11 reversed the effects of silencing circBBS2 or miR-494 on ferroptosis of SH-SY5Y cells, respectively. Furthermore, UC-MSCs-derived exosomes attenuated ischemic stroke in rats via delivering circBBS2 to inhibit ferroptosis. UC-MSCs-derived exosomal circBBS2 enhanced SLC7A11 expression via sponging miR-494, therefore repressing ferroptosis and relieving ischemic stroke. Our findings shed light on a novel mechanism for UC-MSCs-derived exosomes in the treatment of ischemic stroke.

Unique association of anti-GABAA receptor encephalitis and myasthenia gravis in a patient with type A thymoma.

Association between anti-GABAAR encephalitis and myasthenia gravis is extremely rare with few reported cases. Herein, we report a case of a female patient diagnosed with anti-GABAAR encephalitis and thymoma at the first admission. She was administered glucocorticoids for long-term immunotherapy, and thymectomy with biopsy demonstrated a type A thymoma. After 4 months, the symptoms of encephalitis were relieved, but she then developed post-thymectomy myasthenia gravis with anti-AChR and anti-titin dual positivity. Antibodies to connective tissue (anti-ANA, anti-PCNA) and those characteristics of paraneoplastic syndrome (anti-Ma2/Ta) were also positive. She received oral glucocorticoids and tacrolimus as immunosuppressive therapy, and myasthenic symptoms were stable during a 2-year follow-up. Our case revealed that anti-GABAAR encephalitis and myasthenia gravis can appear in patient with type A thymoma at different periods, which alerts physicians to take long-term follow-up for anti-GABAAR encephalitis with thymoma, even after thymectomy. Concurrent positivity for more than one antibody after thymectomy is rarely observed, and their contribution to the clinical course and treatment decision remains to be further investigated.

Aerobic exercise improves cognitive impairment in mice with type 2 diabetes by regulating the MALAT1/miR-382-3p/BDNF signaling pathway in serum-exosomes.

BACKGROUND: It has been documented that aerobic exercise (AE) has a positive effect on improving cognitive function in type 2 diabetes (T2DM) patients. Here, we tried to explore how AE regulates the expression of long non-coding RNA in serum-exosomes (Exos), thereby affecting cognitive impairment in T2DM mice as well as its potential molecular mechanism. METHODS: T2DM mouse models were constructed, and serum-Exos were isolated for whole transcriptome sequencing to screen differentially expressed lncRNA and mRNA, followed by prediction of downstream target genes. The binding ability of miR-382-3p with a long non-coding RNA MALAT1 and brain-derived neurotrophic factor (BDNF) was explored. Then, primary mouse hippocampal neurons were collected for in vitro mechanism verification, as evidenced by the detection of hippocampal neurons' vitality, proliferation, and apoptosis capabilities, and insulin resistance. Finally, in vivo mechanism verification was performed to assess the effect of AE on insulin resistance and cognitive disorder. RESULTS: Transcriptome sequencing analysis showed that MALAT1 was lowly expressed and miR-382-3p was highly expressed in serum-Exos samples of T2DM mice. There were targeted binding sites between MALAT1 and miR-382-3p and between miR-382-3p and BDNF. In vitro experiments showed that MALAT1 upregulated BDNF expression by inhibiting miR-382-3p. Silencing MALAT1 or overexpressing miR-382-3p could reduce the expression of INSR, IRS-1, IRS-2, PI3K/AKT, and Ras/MAPK, inhibit neuronal proliferation, and promote apoptosis. In vivo experiments further confirmed that AE could increase the expression of MALAT1 in serum-Exos to competitively inhibit miR-382-3p and upregulate BDNF expression, thereby improving cognitive impairment in T2DM mice. CONCLUSION: AE may upregulate the expression of MALAT1 in serum-Exos to competitively inhibit miR-382-3p and upregulate BDNF expression, thus improving cognitive impairment in T2DM mice.

[Expression of Ephrin-B2 after focal cerebral ischemia in rats].

OBJECTIVE: To explore the expression profile of Ephrin-B2 in the ischemic penumbra after transient focal cerebral ischemia in rats, and to clarify the mechanism of Ephrin-B2 triggering angiogenesis. METHODS: Sprague-Dawley rats were randomly divided into a normal group, a sham operation group and ischemic-reperfusion 1, 3, 7, 14, and 28 d groups. Suture-occluded method was used to establish the focal middle cerebral artery occlusion model and the ischemic brain was reperfused 2 h after the occlusion. Western blot and quantitative real-time reverse-transcription polymerase chain reaction were used to detect the dynamic expression profile of Ephrin-B2 in the penumbra cortex. Double immunofluorescence was used to speculate the location and the co-expression of Ephrin-B2 in blood vessels, neurons and astrocytes. Microvessel density was quantified by the number of CD31+ cells. Rats were subjected to neurologic functional tests by modified neurological severity scores (mNSS) before sacrifice. RESULTS: Compared with the sham group, Ephrin-B2 protein and mRNA level of the penumbra cortex in the ischemic group increased 3 days (P<0.05) after the reperfusion, peaked at day 7 and 14 (P<0.01), and declined at day 28. Double immunofluorescence indicated that Ehprin-b2 was expressed in the neurons, blood vessels and astrocytes; mNSS peaked at day 7, and gradually declined at day 14. The microvessel density of penumbra cortex in the ischemic group increased 3 days (P<0.05) after the reperfusion, peaked at day 14 (P<0.01), and gradually declined at 48 h. CONCLUSION: Cerebral ischemia reperfusion induces the over-expression of Ephrin-B2, with a dynamic trend, suggesting that Ehprin-b2 may improve post-stroke functional recovery by enhancing angiogenesis and neurogenesis.

Antithrombin deficiency caused by SERPINC1 gene mutation in white matter lesions: A case report.

RATIONALE: White matter lesions (WMLs) are structural changes in the brain that manifest as demyelination in the central nervous system pathologically. Vasogenic WMLs are the most prevalent type, primarily associated with advanced age and cerebrovascular risk factors. Conversely, immunogenic WMLs, typified by multiple sclerosis (MS), are more frequently observed in younger patients. It is crucial to distinguish between these 2 etiologies. Furthermore, in cases where multiple individuals exhibit WMLs within 1 family, genetic testing may offer a significant diagnostic perspective. PATIENT CONCERNS: A 25-year-old male presented to the Department of Neurology with recurrent headaches. He was healthy previously and the neurological examination was negative. Brain magnetic resonance imaging (MRI) showed widespread white matter hyperintensity lesions surrounding the ventricles and subcortical regions on T2-weighted and T2 fluid-attenuated inversion recovery images, mimicking immunogenic disease-MS. DIAGNOSES: The patient was diagnosed with a patent foramen ovale, which could explain his headache syndrome. Genetic testing unveiled a previously unidentified missense mutation in the SERPINC1 gene in the patient and his father. The specific abnormal laboratory finding was a reduction in antithrombin III activity, and the decrease may serve as the underlying cause for the presence of multiple intracranial WMLs observed in both the patient and his father. INTERVENTIONS: The patient received percutaneous patent foramen ovale closure surgery and took antiplatelet drug recommended by cardiologists and was followed up for 1 month and 6 months after operation. OUTCOMES: While the lesions on MRI remain unchanging during follow-up, the patient reported a significant relief in headaches compared to the initial presentation. LESSONS: This case introduces a novel perspective on the etiology of cerebral WMLs, suggesting that hereditary antithrombin deficiency (ATD) could contribute to altered blood composition and may serve as an underlying cause in certain individuals with asymptomatic WMLs.

BMSC-derived exosomal miR-148b-3p attenuates OGD/R-induced HMC3 cell activation by targeting DLL4 and Notch1.

Bone mesenchymal stem cell (BMSC)-derived exosome (BMSC-Exo) could be a treatment method for ischemic injury. In ischemic cerebrovascular disease (IC), microglia is pivotal in neuronal damage and remodeling. This study explores the mechanisms of BMSC-Exo miR-148b-3p in regulating oxygen-glucose deprivation/reoxygenation (OGD/R)-induced human microglial clone 3 (HMC3) cell activation. Transmission electron microscopy (TEM) and qNano were used to assess BMSC-Exo features. The functions of BMSC-Exo miR-148 b-3p in OGD/R-induced HMC3 cell activation were explored via MTT assay, flow cytometry, scratch, transwell, and enzyme-linked immunosorbent assay (ELISA) assays. A dual-luciferase reporter assay was performed to determine the relationship between miR-148b-3p and Delta-like ligand 4(DDL4) or neurogenic locus notch homolog protein 1 (Notch1). OGD/R decreased miR-148b-3p expression in HMC3 cells. After BMSC-Exo treatment, miR-148b-3p expression was upregulated, cell viability and migration were inhibited, cell cycles remained in the G0/G1 phase, and proinflammatory cytokines were decreased in OGD/R-induced HMC3 cells. More importantly, BMSC-Exo miR-148b-3p could further strengthen BMSC-Exo effects. DDL4 and Notch1 are direct targets of miR-148b-3p, respectively. Moreover, the knockdown of DLL4 or Notch1 could inhibit OGD/R-induced HMC3 cell activation. BMSC-Exo miR-148b-3p inhibited OGD/R-induced HMC3 cell activation via inhibiting DLL4 and Notch1 expression, which provided a new strategy for treating cerebral ischemia.

Mapping the global research landscape and trends of autoimmune encephalitis: A bibliometric analysis.

Background: Autoimmune encephalitis (AE) is a neuroautoimmune disease featured by the presence of antibodies targeting neuronal surface, synaptic, or intracellular antigens. An increasing number of articles on its clinical manifestations, treatments, and prognosis have appeared in recent years. The objectives of this study were to summarize this growing body of literature and provide an overview of hotspots and trends in AE research using bibliometric analysis. Methods: We retrieved AE-related articles published between 1999 and 2022 from the Web of Science Core Collection. Using bibliometric websites and software, we analyzed the data of AE research, including details about countries, institutions, authors, references, journals, and keywords. Results: We analyzed 3348 articles, with an average of 32.83 citations per article and an H-index of 141. The USA (1091, 32.587%), China (531, 15.860%), Germany (447, 13.351%), England (266, 7.945%), and Japan (213, 6.362%) had the greatest numbers of publications. The top five institutions by numbers of publications were Oxford (143, 4.271%), the Udice French Research Universities (135, 4.032%), the University of Pennsylvania (135, 4.032%), l'Institut National de la Sante de la Recherche Medicale Inserm (113, 3.375%), and the University of Barcelona (110, 3.286%). The most productive authors were J. Dalmau (98, 2.927%), A. Vincent (65, 2.479%), H. Pruess (64, 1.912%), C. G. Bien (43, 1.284%), and F. Graus (43, 1.284%). "autoimmune encephalitis" was the most frequently used keyword (430), followed by "antibodies" (420), "NMDA receptor encephalitis" (383), and "limbic encephalitis" (368). In recent years, research hotspots have focused on the diagnosis and immunotherapy of NMDAR encephalitis and on limbic encephalitis. Conclusion: Developed Western countries have made significant contributions to this field. China has shown a steady increase in the number of publications in recent years, but the quality and influence of these articles warrant efforts at improvement. Future directions in AE research lie in two key areas: (i) the clinical manifestations, prevalence, and prognosis of AE (enabled by advances in diagnosis); and (ii) the efficacy and safety of targeted, individualized immunotherapy.

USP18 Stabilized FTO Protein to Activate Mitophagy in Ischemic Stroke Through Repressing m6A Modification of SIRT6.

Ischemic stroke (IS) is a dangerous cerebrovascular disorder with a significant incidence and death rate. Ubiquitin-specific peptidase 18 (USP18) has been proven to mitigate ischemic brain damage; however, its potential regulatory mechanisms remain unclear. In vivo and in vitro models of IS were established by middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R). Neurocyte injury was detected by MTT, LDH, ROS level, mitochondrial membrane potential (Δψm), and flow cytometry. Molecular expression was evaluated by qPCR, Western blotting, and immunofluorescence staining. Molecular mechanisms were determined by Co-IP, RIP, and MeRIP. IS injury was determined by neurological behavior score and TTC staining. Mitophagy was observed by TEM. USP18 and fat mass and obesity-associated protein (FTO) expression declined after OGD/R. Dysfunctional mitochondrial and apoptosis in OGD/R-stimulated neurocytes were eliminated by USP18/FTO overexpression via mitophagy activation. USP18-mediated de-ubiquitination was responsible for increasing FTO protein stability. Up-regulation of FTO protein restrained m6A modification of sirtuin6 (SIRT6) in a YTHDF2-dependent manner to enhance SIRT6 expression and subsequent activation of AMPK/PGC-1α/AKT signaling. FTO induced mitophagy to ameliorate nerve cell damage through SIRT6/AMPK/PGC-1α/AKT pathway. Finally, USP18/FTO overexpression relieved IS in rats via triggering SIRT6/AMPK/PGC-1α/AKT axis-mediated mitophagy. USP18 increased FTO protein stability to trigger SIRT6-induced mitophagy, thus mitigating IS. Our data unravel the novel neuroprotective mechanism of USP18 and suggest its potential as a promising treatment target for IS.

TNFSF4 gene polymorphism rs3861950 but not rs3850641 is associated with the risk of cerebral infarction in a Chinese population.

Tumor necrosis factor superfamily member 4 (TNFSF4) plays a key role in the process of atherosclerosis, a common risk factor for both myocardial and cerebral infarctions. Recent studies indicate that the single nucleotide polymorphism (SNP) rs3850641 in TNFSF4 is associated with higher risk of myocardial infarction, but little is known about the association between TNFSF4 variation and cerebral infarction (CI). A case-control study involving 385 CI patients and 385 age-matched, sex-matched non-CI controls was conducted in a Chinese population, only the most common subtype, atherosclerosis CI, was recruited. Two SNPs of TNFSF4, rs3850641 and rs3861950, were genotyped by the TaqMan SNP genotyping method, and verified partly by genomic DNA sequencing. The results revealed a significant allelic association between rs3861950 and CI (Odds ration = 1.733, 95 % confidence interval = 1.333-2.254, P = 0.000). Genotypic association analysis demonstrated that the CC genotype of rs3861950 confers susceptibility to CI (Odds ration = 2.896, 95 % confidence interval = 1.368-6.132), and it was associated with a significantly higher risk of ischemic stroke (Odds ration = 3.520, 95 % confidence interval = 1.546-8.015, P = 0.003) after adjusting for the other confirmed risk factors such as the history of hypertension, diabetes, CAD, smoking and alcohol drinking. While the odds ratio of the T allele to the C allele was 1.733 (95 % confidence interval: 1.333-2.254). However, there was no significant association between rs3850641 and CI (Odds ration = 1.288, 95 % confidence interval = 0.993-1.670, P = 0.056). TNFSF4 gene polymorphism rs3861950, but not rs3850641, is associated with the risk of atherosclerosis CI in a Chinese population.

Relationship between insulin-like growth factor-1 and cerebral small vessel disease and its mechanisms: advances in the field.

Insulin-like growth factor-1 (IGF-1) is an active polypeptide protein that closely resembles the structural sequence of insulin and is involved in a variety of metabolic processes in the body. Decreased IGF-1 circulation levels are associated with an increased risk of stroke and a poorer prognosis, but the relationship with cerebral small vessel disease (cSVD) is unclear. Some studies found that the level of IGF-1 in patients with cSVD was significantly reduced, but the clinical significance and underlying mechanisms are unknown. This article reviews the correlation between IGF-1 and cerebrovascular disease and explores the potential relationship and mechanism between IGF-1 and cSVD.

Biomarkers in cerebrospinal fluid for amyotrophic lateral sclerosis phenotypes.

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving both upper and lower motor neurons. The motor phenotypes of ALS are highly clinically heterogeneous, and the underlying mechanisms are poorly understood. METHODS: A comparative proteomic analysis was performed in the cerebrospinal fluid (CSF) of bulbar-onset (BO) and spinal-onset (SO) ALS patients and controls (n = 14). Five biomarker candidates were selected from a differentially regulated protein pool, and further validation was performed in a larger independent cohort (n = 92) using enzyme-linked immunosorbent assay (ELISA). RESULTS: A total of 1732 CSF proteins were identified, and 78 differentially expressed proteins were found among BO-ALS patients, SO-ALS patients, and controls. Five promising biomarker candidates were selected for further validation, and lipopolysaccharide-binding protein (LBP) and HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA) were validated. CSF LBP levels were increased in ALS patients compared with controls and higher in BO-ALS versus SO-ALS. The increased CSF LBP levels were correlated with the revised ALS Functional Scale (ALSFRS-R) score. CSF HLA-DRA levels were specifically elevated in BO-ALS patients, and there was no significant difference between SO-ALS patients and controls. Increased HLA-DRA expression was correlated with decreased survival. INTERPRETATION: Our data shows that elevated CSF LBP is a good biomarker for ALS and correlates with clinical severity, and increased HLA-DRA is a specific biomarker for BO-ALS and may predict short survival. It also suggests that the microglial pathway and HLA-II-related adaptive immunity may be differentially involved in ALS phenotypes and may be new therapeutic targets for ALS.

Energy restriction induced SIRT6 inhibits microglia activation and promotes angiogenesis in cerebral ischemia via transcriptional inhibition of TXNIP.

Energy restriction (ER) protects against cerebral ischemic injury, but the underlying mechanism remains largely unclear. Here, rats were fed ad libitum (AL) or on an alternate-day food deprivation intermittent fasting (IF) diet for 3 months, followed by middle cerebral artery occlusion (MCAO) surgery. The body weight, infarct volume, and neurological deficit score were accessed at the designated time points. ELISA, qRT-PCR, and Western blotting were used to determine cytokine secretion and the expression of SIRT6, TXNIP, and signaling molecules, respectively. Immunofluorescence evaluated microglial activation and angiogenesis in vivo. For in vitro study, oxygen-glucose deprivation/reoxygenation (OGD/R)-treated cell model was generated. MTT and tube formation assays were employed to determine cell viability and tube formation capability. ChIP assay detected chromatin occupancy of SIRT6 and SIRT6-mediated H3 deacetylation. We found that IF or ER mimetics ameliorated cerebral ischemic brain damage and microglial activation, and potentiated angiogenesis in vivo. ER mimetics or SIRT6 overexpression alleviated cerebral ischemia and reperfusion (I/R)-induced injury in vitro. SIRT6 suppressed TXNIP via deacetylation of H3K9ac and H3K56ac in HAPI cells and BMVECs. Downregulation of SIRT6 reversed ER mimetics-mediated protection during cerebral I/R in vitro. Our study demonstrated that ER-mediated upregulation of SIRT6 inhibited microglia activation and potentiated angiogenesis in cerebral ischemia via suppressing TXNIP.

Stroke-associated infection in patients with co-morbid diabetes mellitus is associated with in-hospital mortality.

Background and objective: The association between infection and acute ischemic stroke (AIS) with diabetes mellitus (DM) remains unknown. Therefore, this study aimed to explore the effect of infection on AIS with DM. Materials and methods: The data of patients with AIS and DM were extracted from the Chinese Stroke Center Alliance (CSCA) database from August 2015 to July 2019. The association between infections [pneumonia or urinary tract infection (UTI)] and in-hospital mortality was analyzed. Logistic regression models were used to identify the risk factors for in-hospital mortality of patients with infection. Results: In total, 1,77,923 AIS patients with DM were included in the study. The infection rate during hospitalization was 10.5%, and the mortality rate of infected patients was 3.4%. Stroke-associated infection was an independent risk factor for an early poor functional outcome [odds ratio (OR) = 2.26, 95% confidence interval (CI): 1.97-2.34, P < 0.0001] and in-hospital mortality in AIS patients with DM. The in-hospital mortality after infection was associated with age (OR = 1.02, 95% CI: 1.01-1.03, P < 0.0001), male (OR = 1.39, 95% CI: 1.13-1.71, P = 0.0018), reperfusion therapy (OR = 2.00, 95% CI: 1.56-2.56, P < 0.0001), and fasting plasma glucose at admission (OR = 1.05, 95% CI: 1.03-1.08, P < 0.0001). In contrast, antiplatelet drug therapy (OR = 0.63, 95% CI: 0.50-0.78, P < 0.0001) and hospital stay (OR = 0.96, 95% CI: 0.94-0.97, P < 0.0001) were independent protecting factors against in-hospital mortality of patients with infection. Conclusion: Infection is an independent risk factor of in-hospital mortality for patients with AIS and DM, and those patients require strengthening nursing management to prevent infection.

Multi-scale microstructure high-strength titanium alloy lattice structure manufactured via selective laser melting.

The tensile performance of Ti6Al4V alloy lattice structure was investigated. Firstly, a face center cubic unit cell with vertical struts (F2CCZ) lattice structure was designed. Then, the structures were fabricated by selective laser melting (SLM) with different aspect ratios. Subsequently, the SLM-ed alloys were subjected to double solution-aging to homogenize the microstructure and release residual stress. It is shown that there is only acicular α' martensite with high dislocation density in the SLM-ed alloy, while the heat-treated alloy has α and ß phases (there are multi-scale α laths and nano-scale ß particles), and the orientation relationship between the two phases is: [113]ß//[1210]α. The tensile strength of the HT-ed alloys presents a significant increase from 140 ± 18 MPa in the SLM-ed state to 229 ± 5.1 MPa with an aspect ratio of 4. It indicates that the special heat treatment regime can not only homogenize the microstructure of the SLM-ed alloy, but also improve the tensile strength.

[Negative association of FGA gene 128C/G polymorphism with cerebral infarction and its effect on plasma fibrinogen in Hunan Hans].

OBJECTIVE: To investigate the relationship of FGA gene 128C/G polymorphism and cerebral infarction (CI) and evaluate the effect of FGA-128C/G polymorphism on plasma fibrinogen in Hunan Hans. METHODS: FGA-128C/G polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing in 194 CI patients and 114 healthy controls. RESULTS: There were CG and CC genotypes in the FGA-128C/G locus. No GG genotype was observed in Hunan Hans. There was no significant difference in genotype and allele frequencies between the controls and CI group (P> 0.05), and statistically significant difference was not found in fibrinogen (Fg) level between the CG and CC genotypes (P>0.05). After analyzing blood plasma Fg using the influencing factor multiple regression analysis, it was shown that the Fg level had no relationship with the FGA-128C/G genotype, but it increased with age. And the Fg level in males was higher than that in females. CONCLUSION: There was FGA gene 128C/G polymorphism in the Hunan Han population. There was no association of this polymorphism with the increased Fg level of CI patient in the population. FGA-128C/G might not be the predisposing gene of CI in Hunan Han population. The age and sex were the major factors affecting the plasma Fg level in this population.

Could Sporadic Creutzfeldt-Jakob Disease Be Underdiagnosed in China? Experience From Four Cases.

Background: Creutzfeldt-Jakob Disease (CJD) is a rapidly progressive neurodegenerative disease caused by the misfolded version of the cellular prion protein. Here we report four cases of sporadic CJD (sCJD) and describe the diagnostic methods available in order avoid missed or delayed recognition of CJD in China. Case presentation: We report four patients diagnosed with sCJD between March 2018 and December 2019 at Xiangya Hospital and the Second Xiangya Hospital of Central South University. All patients were admitted to the hospital because of a progressive cognitive decline. Although their routine tests and biochemical indicators in the cerebrospinal fluid (CSF), as well as computed tomography (CT) imaging, did not reveal any apparent abnormalities, the presence of "cortical ribboning" was incidentally found on diffusion-weighted imaging (DWI). The patients were subsequently diagnosed with CJD based on positive testing for 14-3-3 protein in their CSF, and the presence of periodic sharp and slow wave complexes (PSWCs) on their electroencephalograms (EEG). Additionally, two of patients was confirmed pathological examination of cerebral biopsies demonstrating neuronal loss, gliosis, and spongiform changes. Conclusions: CJD is a rare disease and is easily misdiagnosed by clinician in China due to a lack of recognition and awareness of CJD. Based on our experience described in this report, enhanced vigilance for CJD is required for patients with rapidly progressive dementia in China and other developing countries. DWI, EEG and detection of 14-3-3 protein in CSF should be performed in order to achieve a timely diagnosis of CJD.

Influences of Low Intensity on Diode Parameters of CdTe Solar Cells.

This study deals with the CdS/CdTe solar cells under low illumination intensity, with cell #1 for the shunt resistance exceeding 100,000 Ω·cm2 and cell #2 for the shunt resistance above 1000 Ω·cm2. The diode parameter variations with the decline of the irradiance intensity are illustrated by dividing 0-100 mW/cm-2 into a number of small intensity ranges for J-V measurements and assuming the diode parameters to be constant within each range, the diode parameters of each range including the series resistance, the shunt resistance, the reverse saturation current density and the ideality factor are then extracted by employing an analytical approach. The mechanism of the cell performance deviations are also investigated by basic theories, reports and experiments. For cell #1 with higher Rsh corresponding to less traps, Rsh shows a upward tendency asthe irradiance declines, n and J0 exhibit a rise with the irradiance and keep nearly unchanged at the low irradiance values mainly due to recombination and carrier contributions, Rs shows a slight increase when the irradiance intensity goes down because of the resistance of CdTe absorption layer. For cell #2 with lower Rsh corresponding to more traps, with the decrease of the illumination intensity, Rsh increases sharply only for captured carrier reduction, Rs goes steadily up similarly, n and J0 exhibit a decline with the irradiance due to recombination shift. It should be pointed out that Rs varies much smoother than the traditional approximation of a reciprocal of differential at short circuit, and the distribution of Rsh is diverse, and an average Rsh of for each intensity range can reflect the variation trend.

Broadband High-Efficiency Grating Couplers for Perfectly Vertical Fiber-to-Chip Coupling Enhanced by Fabry-Perot-like Cavity.

We propose a broadband high-efficiency grating coupler for perfectly vertical fiber-to-chip coupling. The up-reflection is reduced, hence enhanced coupling efficiency is achieved with the help of a Fabry-Perot-like cavity composed of a silicon nitride reflector and the grating itself. With the theory of the Fabry-Perot cavity, the dimensional parameters of the coupler are investigated. With the optimized parameters, up-reflection in the C-band is reduced from 10.6% to 5%, resulting in an enhanced coupling efficiency of 80.3%, with a 1-dB bandwidth of 58 nm, which covers the entire C-band. The minimum feature size of the proposed structure is over 219 nm, which makes our design easy to fabricate through 248 nm deep-UV lithography, and lowers the fabrication cost. The proposed design has potential in efficient and fabrication-tolerant interfacing applications, between off-chip light sources and integrated chips that can be mass-produced.

Identification of expanded repeats in NOTCH2NLC in neurodegenerative dementias.

Recently, the (GGC)n repeat expansion in the NOTCH2NLC gene has been identified to be associated with neuronal intranuclear inclusion disease (NIID). Given the clinical overlap of dementia-dominant NIID with neurodegenerative dementia, we therefore hypothesized that the NOTCH2NLC repeat expansion might also contribute to these diseases. In the present study, repeat primed polymerase chain reaction (RP-PCR) and GC-rich PCR were conducted to detect the repeats of NOTCH2NLC in a cohort of 1004 patients with neurodegenerative dementias from mainland China. As a result, 4 sporadic patients were found to carry the NOTCH2NLC repeats expansion, totally accounting for 0.4% of all dementia individuals, and the accurate repeated sizes were 110, 133,120 and 76 respectively. Of 4 mutation carriers, three and one were clinically diagnosed Alzheimer's disease (AD) and frontotemporal dementia (FTD) respectively. In addition, 3 out of them revealed leukoencephalopathy in T2-Flair imaging. This study revealed that although rare, the NOTCH2NLC repeat expansions may be associated with AD or FTD-like phenotype as well as leukoencephalopathy.