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1.
Nanoscale ; 16(41): 19276-19283, 2024 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-39354809

RESUMO

Two-dimensional multiferroic materials that exhibit both ferroelectricity and ferromagnetism provide a new platform for the discovery and regulation of magnetic skyrmions. In this study, we utilize first-principles calculations and Monte Carlo simulations to explore the properties and regulation of magnetic skyrmions in a novel multiferroic monolayer, MnOBr. MnOBr exhibits skyrmions without the need for an external magnetic field. Upon applying an external magnetic field, we found the disappearance of labyrinth domains and the formation of a periodic arrangement of the skyrmion lattice. By employing machine learning techniques, we depict a phase diagram of MnOBr under varying magnetic fields and biaxial strain, which provides a detailed depiction of phase transitions of spin textures in monolayer MnOBr. Furthermore, in MnOBr/CdClBr heterostructures, we demonstrate that the creation and annihilation of magnetic skyrmions can be controlled by switching the polarization direction of the Janus CdClBr. These findings show potential applications of MnOBr as a 2D magnetic skyrmion material in spintronic devices.

2.
Neurol Sci ; 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39356377

RESUMO

BACKGROUND: Idiopathic extracranial internal carotid artery vasospasm (IEICAV) is characterized by spontaneous, recurrent, and reversible vasoconstriction of the cervical internal carotid artery (ICA). The etiology remains elusive, and no effective treatment has been established. The present study presents a case of recurrent IEICAV with migraine-like symptoms and conduct a systematic review on IEICAV. METHODS: A retrospective analysis was conducted on a case involving medical history, radiological data, treatment, and outcomes. A systematic review of published IEICAV cases was conducted through database searching in PubMed, Embase, and Web of Science from inception until May 2024. RESULTS: A 22-year-old female with recurrent headaches, blurred vision, and aphasia was diagnosed with bilateral IEICAV through angiography. Magnetic resonance imaging demonstrated a novel cerebral infarction during a prolonged episode. Treatment with topiramate successfully controlled recurrence in a 5-month follow-up. The systematic review included 36 IEICAV cases reported by literature. Bilateral involvement of extracranial ICAs was observed in 25 (69.4%) cases. Cerebral infarction was identified in 31 (88.9%) cases. Despite various treatment attempts including vasodilators, antiplatelet, anticoagulants, glucocorticoids, and other medical or surgical intervention, the recurrent rate increased in 5 (13.9%) cases, decreased in 10 (27.8%) cases, and remained unchanged in 4 (11.1%) cases. CONCLUSIONS: The elusive mechanism of IEICAV brings great difficulty into managing recurrence. Preventing IEICAV-related infarction related to secondary factors like hypoperfusion may be crucial for maintaining life quality. Further research is essential for advancing treatment strategies and a case-by-case approach is needed in identifying and eliminating possible triggers for vasospastic episodes.

3.
BMC Complement Med Ther ; 24(1): 349, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39358731

RESUMO

BACKGROUND: Post-stroke cognitive impairment (PSCI) not only increases patient mortality and disability, but also adversely affects motor function and the ability to perform routine daily activities. Current therapeutic approaches for, PSCI lack specificity, primarily relying on and medication and traditional cognitive therapy supplemented by a limited array of tools. Both transcranial direct current stimulation (tDCS) and virtual reality (VR) training have demonstrated efficacy in improving cognitive performance among PSCI patients. Previous findings across various conditions suggest that implementing a therapeutic protocol combining tDCS and VR (tDCS - VR) may yield superior in isolation. Despite this, to our knowledge, no clinical investigation combining tDCS and VR for PSCI rehabilitation has been conducted. Thus, the purpose of this study is to explore the effects of tDCS - VR on PSCI rehabilitation. METHODS: This 4-week, single-center randomized clinical trial protocol will recruit 200 patients who were randomly assigned to one of four groups: Group A (tDCS + VR), Group B (tDCS + sham VR), Group C (sham tDCS + VR), Group D (sham tDCS + sham VR). All four groups will receive conventional cognitive rehabilitation training. The primary outcome measurement utilizes the Mini-Mental State Examination (MMSE). Secondary outcome measures include the Montreal Cognitive Assessment, Frontal Assessment Battery, Clock Drawing Test, Digital Span Test, Logic Memory Test, and Modified Barthel Index. Additionally, S-YYZ-01 apparatus for diagnosis and treating language disorders assesses subjects' speech function. Pre- and post-four-week intervention assessments are conducted for all outcome measures. Functional near-infrared spectroscopy (fNIRS) is employed to observe changes in oxygenated hemoglobin (HbO), deoxy-hemoglobin (HbR), and total hemoglobin (HbT) in the cerebral cortex. DISCUSSION: Our hypothesis posits that the tDCS - VR therapy, in opposed to individual tDCS or VR interventions, could enhance cognitive function, speech ability and daily living skills in PSCI patients while concurrently augmenting frontal cortical activity. This randomized study aims to provide a robust theoretical foundation supported by scientific evidence for the practical implementation of the tDCS - VR combination as a secure and efficient PSCI rehabilitation approach. TRIAL REGISTRATION: Chictr.org.cn Identifier: ChiCTR2300070580. Registered on 17th April 2023.


Assuntos
Disfunção Cognitiva , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Estimulação Transcraniana por Corrente Contínua , Realidade Virtual , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Disfunção Cognitiva/terapia , Disfunção Cognitiva/etiologia , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/complicações , Feminino , Masculino , Terapia de Exposição à Realidade Virtual/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Idoso , Pessoa de Meia-Idade , Adulto , Terapia Combinada
5.
Int Immunopharmacol ; 143(Pt 1): 113236, 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39378654

RESUMO

INTRODUCTION: Immunogenic cell death (ICD) is a unique cell death triggered by chemotherapy. However, studies elucidating the potential therapeutic role of ICD and the underlying mechanism in diabetic nephropathy (DN) are limited. METHODS: WGCNA was conducted on the human kidney biopsy data linked to DN, analyzing gene sets associated with ICD. Gene Set Enrichment Analysis and Gene Set Variation Analysis were utilized to examine the discrepancy in biological function. We used Gene Ontology, the Kyoto Encyclopedia of Genes and Genomes, and the GeneMANIA database to investigate the function of the signature genes. An analysis using the receiver operating characteristic (ROC) was conducted to validate the diagnostic value of hub genes. Additionally, immune infiltration-related analyses were also performed. In conclusion, we examined the association between the glomerular filtration rate, serum creatinine, and hub genes. Hub genes were validated by immunohistochemistry using db/db mice kidneys. RESULTS: WGCNA revealed that the targets in the turquoise unit (1674 genes) exhibited the highest positive correlation with ICD. Furthermore, 4222 statistically significant DEGs were identified when comparing the DN and healthy control groups. Significantly, the KEGG pathway enrichment analysis indicated a connection between ICD and the nuclear factor-kappa B signaling pathway and the synthesis of cytokines (tumor necrosis factor superfamily). ROC analysis revealed that 16 hub genes exhibited strong discriminatory potential as biomarkers for DN. Therefore, immunohistochemical validation, with the potential involvement of chemokines (CCL11, CCR2, CCR7, CX3CR1, CXCL10, CXCL12, and CXCR5) and immune cells (CD3G, CD5, and CD247) may be crucial for the diagnosis and therapy of DN. CONCLUSIONS: DKK3, NR4A1, NR4A2, VEGFA, and DUSP1 may be associated with the development of DN. The pathogenesis of DN may specifically involve chemokines (CCL11, CCR2, CCR7, CX3CR1, CXCL10, CXCL12, and CXCR5) and immune cells (CD3G, CD5, and CD247), with LCP2 playing a significant role.

6.
Front Med (Lausanne) ; 11: 1419356, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39219789

RESUMO

The genus Salmonella consists of Gram-negative bacteria with various serotypes. It commonly causes bacterial infections that affect the intestines. Infection can occur in humans and animals through the ingestion of contaminated food or water, or through contact with infected animals or environments. Complications commonly include intestinal hemorrhage and perforation, though vertebral osteomyelitis is rarely observed. Therefore, in patients with spinal cord abscesses, The genus Salmonella is typically not considered a likely pathogen, especially in the absence of typical symptoms. In this case, the limited information provided by traditional cultivation methods, particularly under the influence of antibiotics. However, next-generation sequencing (NGS) unexpectedly detected Salmonella, which assisted in formulating the final treatment plan. This underscores the role and clinical value of NGS in pathogen identification.

7.
BMC Cardiovasc Disord ; 24(1): 510, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39327565

RESUMO

OBJECTIVE: This study investigated the relationship of serum homocysteine (Hcy) and cystatin C (Cys C) levels with the prognosis of patients with heart failure with preserved ejection fraction (HFpEF). METHODS: A total of 178 patients with HFpEF who were admitted to our hospital between December 2019 and November 2020 were included. Patients were grouped based on their serum Hcy and Cys C levels: high Hcy level, normal Hcy level, high Cys C level, and normal Cys C level. Cardiac function, ventricular remodeling indices, and prognosis were compared among patients in these groups. Additionally, the predictive value of serum Hcy and Cys C levels for adverse cardiovascular events in HFpEF patients was analyzed. RESULTS: Patients' mean age in the high Hcy level, normal Hcy level, high Cys C level, and normal Cys C level groups was 69.21 ± 4.17,67.74 ± 4.28,69.95 ± 4.98, and 67.06 ± 4.13 years old, respectively. The high Hcy level group exhibited a lower proportion of class II cardiac function according to the New York Heart Association (NYHA) classification and a higher proportion of class IV cardiac function than the normal Hcy level group, with statistically significant differences. Similarly, the high Cys C level group had a lower proportion of class II cardiac function and a higher proportion of class IV cardiac function compared with the normal Cys C level group, with statistically significant differences. Left ventricular end-diastolic internal diameter (LVEDD), left ventricular end-systolic internal diameter (LVESD), and left ventricular mass index (LVMI) were significantly higher in both the high Hcy level and high Cys C level groups compared with the normal group, with statistically significant differences. The rates of all-cause mortality and class I endpoint events were significantly higher in the high Hcy level and high Cys C level groups than in the normal group. Multifactorial logistic regression analysis demonstrated that adverse cardiovascular events were significantly associated with cardiac function class, LVEDD, LVESD, LVMI, Hcy, and Cys C in patients with HFpEF. The area under the curve (AUC) values for Hcy and Cys C, determined using receiver operating characteristic (ROC) curve analysis, were 0.778 (optimal critical value, 25.38) and 0.681 (optimal critical value, 1.56), respectively, for predicting adverse cardiovascular events. Both Hcy and Cys C serum levels were positively correlated with LVEDD, LVESD, LVMI, and NYHA classification. CONCLUSION: Serum levels of Hcy and Cys C were closely associated with cardiac function, ventricular remodeling indices, and prognosis in patients with HFpEF. These levels may serve as valuable indices for assessing HFpEF patients' health status and prognosis, providing important insights into their potential role as biomarkers for HFpEF management and prognosis.


Assuntos
Biomarcadores , Cistatina C , Insuficiência Cardíaca , Homocisteína , Valor Preditivo dos Testes , Volume Sistólico , Função Ventricular Esquerda , Humanos , Homocisteína/sangue , Cistatina C/sangue , Masculino , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Biomarcadores/sangue , Idoso , Prognóstico , Pessoa de Meia-Idade , Medição de Risco , Estudos Retrospectivos , Remodelação Ventricular , Fatores de Risco
8.
BMC Neurol ; 24(1): 328, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39243002

RESUMO

BACKGROUND: Intracranial artery stenosis (ICAS) and cerebral small vessel disease (CSVD) are associated with a heavy socioeconomic burden; however, their longitudinal changes remain controversial. METHODS: We conducted a longitudinal analysis on 756 participants of Shunyi Cohort who underwent both baseline and follow-up brain magnetic resonance imaging (MRI) and MR angiography in order to investigate the risk factors for ICAS and CSVD progression in community population. Incident ICAS was defined as new stenosis occurring in at least one artery or increased severity of the original artery stenosis. CSVD markers included lacunes, cerebral microbleeds (CMB), and white matter hyperintensities (WMH). RESULTS: After 5.58 ± 0.49 years of follow-up, 8.5% of the 756 participants (53.7 ± 8.0 years old, 65.1% women) had incident ICAS. Body mass index (BMI) (OR = 1.09, 95% CI = 1.01-1.17, p = 0.035) and diabetes mellitus (OR = 2.67, 95% CI = 1.44-4.93, p = 0.002) were independent risk factors for incident ICAS. Hypertension was an independent risk factor for incident lacunes (OR = 2.12, 95% CI = 1.20-3.77, p = 0.010) and CMB (OR = 2.32, 95% CI = 1.22-4.41, p = 0.011), while WMH progression was primarily affected by BMI (ß = 0.108, SE = 0.006, p = 0.002). A higher LDL cholesterol level was found to independently protect against WMH progression (ß = -0.076, SE = 0.027, p = 0.019). CONCLUSIONS: Modifiable risk factor profiles exhibit different in patients with ICAS and CSVD progression. Controlling BMI and diabetes mellitus may help to prevent incident ICAS, and antihypertensive therapy may conduce to mitigate lacunes and CMB progression. LDL cholesterol may play an inverse role in large arteries and small vessels.


Assuntos
Doenças de Pequenos Vasos Cerebrais , Progressão da Doença , Humanos , Masculino , Doenças de Pequenos Vasos Cerebrais/epidemiologia , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Estudos Longitudinais , Imageamento por Ressonância Magnética/métodos , Constrição Patológica/epidemiologia , Adulto , Idoso , Hipertensão/epidemiologia , Hipertensão/complicações
9.
Mol Neurobiol ; 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39325100

RESUMO

The genetic transcription profile and underlying molecular mechanisms of ischemic stroke (IS) remain elusive. To address this issue, four mRNA and one miRNA expression profile of rats with middle cerebral artery occlusion (MCAO) were acquired from the Gene Expression Omnibus (GEO) database. A total of 780 differentially expressed genes (DEGs) and 56 miRNAs (DEMs) were screened. Gene set and functional enrichment analysis revealed that a substantial number of immune-inflammation-related pathways were abnormally activated in IS. Through weighted gene co-expression network analysis, the turquoise module was identified as meaningful. By taking the intersection of the turquoise module genes, DEM-target genes, and all DEGs, 354 genes were subsequently obtained as key IS-related genes. Among them, six characteristic genes were identified using the least absolute shrinkage and selection operator. After validation with three external datasets, transforming growth factor beta 1 (Tgfb1) was selected as the hub gene. This finding was further confirmed by gene expression pattern analysis in both the MCAO model rats and clinical IS patients. Moreover, the expression of the hub genes exhibited a negative correlation with the modified Rankin scale score (P < 0.05). Collectively, these results expand our knowledge of the genetic profile and molecular mechanisms involved in IS and suggest that the Tgfb1 gene is a potential biomarker of this disease.

10.
Stroke ; 55(10): 2431-2438, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39315825

RESUMO

BACKGROUND: Branch atheromatous disease (BAD)-related stroke has emerged as a meaningful subtype of ischemic stroke yet remained understudied. We aimed to investigate the demographic, clinical, therapeutic, and prognostic characteristics of BAD-related stroke. METHODS: The BAD-study was a nationwide, multicenter, prospective, observational cohort study in 20 Chinese hospitals from June 2021 to June 2023, enrolling patients aged 18 to 80 years with BAD-related stroke within 72 hours of onset. Eligible single subcortical infarct in the territory of lenticulostriate artery and paramedian pontine artery was included. Clinical, laboratory, and treatment data were collected at baseline. The primary outcome was a proportion of good outcomes (modified Rankin Scale score, 0-2) at 90 days. Main secondary outcomes included early neurological deterioration (END), cerebrovascular event, major bleeding, and excellent outcome (modified Rankin Scale score, 0-1) during 90-day follow-up. RESULTS: We finally enrolled 476 patients, with a median age of 60 (interquartile range, 53-68) years, and 70.2% were male. The median National Institutes of Health Stroke Scale score was 3 (interquartile range, 2-6) at enrollment. Involvement of the lenticulostriate artery was more common than the paramedian pontine artery (60.7% versus 39.3%). END occurred in 14.7% of patients, with a median time from onset of 38 (interquartile range, 22-62) hours. The rates of good and excellent outcomes were 86.5% and 72%, respectively. Its 90-day stroke recurrence rate was 1.9%. Acute-phase therapy (from onset to 7 days of enrollment) showed heterogeneity and was not associated with prognosis. Multivariable logistic regression analysis identified the National Institutes of Health Stroke Scale score ≥4 at admission and END as negative predictors and extracranial artery stenosis as a positive predictor of good outcomes. Age ≥60 years, National Institutes of Health Stroke Scale score ≥4 at admission, and END were negative predictors of excellent outcomes. CONCLUSIONS: With distinct demographic, clinical, and prognostic characteristics, along with a high incidence of END and a low risk of stroke recurrence, BAD-related stroke could be categorized as a separate disease entity. Moreover, its acute-phase treatment strategies were undetermined, awaiting further high-quality studies.


Assuntos
AVC Isquêmico , Imageamento por Ressonância Magnética , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Estudos Prospectivos , Prognóstico , AVC Isquêmico/diagnóstico por imagem , Adulto , Idoso de 80 Anos ou mais , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/epidemiologia
11.
J Stroke Cerebrovasc Dis ; 33(11): 107982, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39233284

RESUMO

BACKGROUND: The relationship between rare variants in Ring finger protein 213 (RNF213) and intracranial atherosclerosis (ICAS) remained unelucidated. Using whole-exome sequencing (WES) and high-resolution magnetic resonance imaging (HR-MRI), this study aimed at investigating the association between rare RNF213 variants and ICAS within a Chinese community-dwelling population. METHODS: The present study included 821 participants from Shunyi cohort. Genetic data of rare RNF213 variants were acquired by WES and were categorized by functional domains. Intracranial and extracranial atherosclerosis were assessed by brain HR-MRI and carotid ultrasound, respectively. Logistic regression and generalized linear regression were applied to evaluate the effects of rare RNF213 variants on atherosclerosis. Stratification by age were conducted with 50 years old set as the cutoff value. RESULTS: Ninety-five participants were identified as carriers of rare RNF213 variants. Carotid plaques were observed in 367 (44.7 %) participants, while ICAS was identified in 306 (37.3 %). Rare variants of RNF213 was not associated with ECAS. Employing HR-MRI, both the presence of rare variants (ß = 0.150, P = 0.025) and numerical count of variants (ß = 0.182, P = 0.003) were significantly correlated with ICAS within the group of age ≤50 years. Both variant existence (ß = 0.154, P = 0.014) and variant count (ß = 0.188, P = 0.003) were significantly associated with plaques in middle cerebral arteries within younger subgroup, rather than basilar arteries. Furthermore, a significant association was observed between variants that located outside the N-arm domain and ICAS in the younger subgroup (OR = 2.522, P = 0.030). Statistical results remained robust after adjusted for age, gender, and cardiovascular risk factors. CONCLUSIONS: Rare variants of RNF213 is associated with age-related ICAS in general Chinese population, highlighting the potential role of RNF213 as a genetic contributor to early-onset ICAS.


Assuntos
Adenosina Trifosfatases , Idade de Início , Predisposição Genética para Doença , Arteriosclerose Intracraniana , Fenótipo , Ubiquitina-Proteína Ligases , Humanos , Ubiquitina-Proteína Ligases/genética , Masculino , Pessoa de Meia-Idade , Feminino , Arteriosclerose Intracraniana/genética , Arteriosclerose Intracraniana/diagnóstico por imagem , Arteriosclerose Intracraniana/etnologia , China/epidemiologia , Adulto , Fatores de Risco , Adenosina Trifosfatases/genética , Estudos de Associação Genética , Sequenciamento do Exoma , Medição de Risco , Idoso , Placa Aterosclerótica/genética , Povo Asiático/genética , Imageamento por Ressonância Magnética , Doenças das Artérias Carótidas/genética , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/etnologia , População do Leste Asiático
12.
J Stroke Cerebrovasc Dis ; 33(11): 107955, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39179190

RESUMO

OBJECTIVES: Intracranial arterial dolichoectasia (IADE) is characterized by the dilation, elongation, and tortuosity of intracranial arteries. We aimed to investigate the association between variations of the Circle of Willis (COW) and IADE in the general population, as well as estimate the genetic correlation between COW variations and IADE. METHODS: A total of 981 individuals from a population-based cohort were included. Brain magnetic resonance angiography was performed to assess COW variants and measure the diameters of intracranial arteries. IADE was defined as a total intracranial volume-adjusted diameter ≥ 2 standard deviations. Logistic regression models were used to analyze the association between COW variations and IADE. The heritability and genetic correlation were estimated using genome-wide complex trait analysis (GCTA) based on single nucleotide polymorphism (SNP) array data. RESULTS: The prevalence of IADE was 6.2 %. Hypoplastic/absent A1 segments were associated with an increase in contralateral ICA diameter (ß ± SE, 0.279 ± 0.049; p = 0.001) and a decrease in ipsilateral ICA diameter (ß ± SE, -0.300 ± 0.050; p = 0.001). Fetal-type posterior cerebral artery (FTP) was associated with a larger ICA diameter (ß ± SE, 0.326 ± 0.048; p = 0.001) and a smaller BA diameter (ß ± SE, -0.662 ± 0.043; p = 0.001). FTP revealed a positive genetic correlation with ICA dilation (rG = 0.259 ± 0.175; p = 0.0009) and a negative genetic correlation with BA dilation (rG = -0.192 ± 0.153, p = 0.015). CONCLUSIONS: There was an association between COW variations and larger intracranial arterial diameters in the general population. Genetic factors may play a role in the development of intracranial arterial dilation and the formation of COW variants.


Assuntos
Círculo Arterial do Cérebro , Predisposição Genética para Doença , Angiografia por Ressonância Magnética , Fenótipo , Polimorfismo de Nucleotídeo Único , Humanos , Círculo Arterial do Cérebro/anormalidades , Círculo Arterial do Cérebro/diagnóstico por imagem , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Fatores de Risco , Prevalência , Idoso , Angiografia Cerebral , Estudo de Associação Genômica Ampla , Dilatação Patológica , Medição de Risco , Hereditariedade , Estudos de Associação Genética , Herança Multifatorial
13.
Eur J Immunol ; : e2451078, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39175123

RESUMO

As cytoplasmic protein complexes that are pivotal for innate immunity, inflammasomes act primarily through the detection of pathogen- or danger-associated molecular patterns. Nucleotide oligomerisation domain-like receptor family and caspase activation recruitment domain-containing protein 4 (NLRC4) inflammasomes identify and eliminate intracellular pathogens, a process contingent on the ligand-recognition capabilities of neuronal apoptosis inhibitory proteins (NAIPs). Upon detection of specific molecules indicative of intracellular infection, NAIPs discern distinct pathogenic components and subsequently transmit signals to NLRC4, thus initiating their activation and triggering an inflammatory response. However, the mechanisms underlying NLRC4 inflammasome remain unclear. In this study, we elucidated the critical role of ATG16L2 in activating the NLRC4 inflammasome. ATG16L2-deficient macrophages exhibited reduced NLRC4 inflammasome activation, characterised by decreased oligomerisation of apoptosis-associated speck-like protein containing a CARD and attenuated cleavage of Pro-caspase-1, Pro-IL-1ß and gasdermin D. Co-immunoprecipitation assays revealed an interaction between ATG16L2 and NAIPs. Furthermore, ATG16L2 enhanced the association between NAIPs and NLRC4 by binding to NAIPs. For ATG16L2-knockout mice infected with Salmonella typhimurium, pathogen clearance and survival rates markedly decreased. Collectively, our findings suggest that ATG16L2 is a significant modulator of the innate immune system, influencing the activity of the NLRC4 inflammasome and the host's defensive response to intracellular pathogens.

14.
ACS Omega ; 9(32): 35113-35130, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39157120

RESUMO

The micropore structure of tight sandstone affects the efficiency of CO2 displacement of crude oil. As the pressure changes, the oil displacement efficiency (E d) in segments with different pore radii changes, and the asphaltene precipitation in the pores causes alterations in the pore structure and wettability, which constrain E d. Ten samples of tight sandstone from the Yanchang Formation in the Ordos Basin were selected for this study. A variety of methods, including X-ray diffraction (XRD), casting thin sections (CTS), scanning electron microscopy (SEM), high-pressure mercury intrusion (HPMI), CT scanning, and nuclear magnetic resonance (NMR) combined with CO2 displacement, were used to study the efficiency of crude oil utilization and the amount of asphaltene deposited at different pore-throat radii, and then the impacts of pressure, pore structure, and wettability changes on E d were discussed. The findings indicate that samples have three types: macropore-fine throats (MF), medium pore-tiny throats (MT), and small pore-microthroats (SM). The MT exhibits a favorable configuration. The pore-throat radius of each sample can be divided into two segments, namely, large pore segments (PL) and small pore segments (PS), and the PL has a significant E d. The E d of the MF-type PS is constrained by pressure. The E d of PL is significantly affected by the pressure sensitivity for the MT, while the E d of PL for the SM structure is more affected by pressure. Changes in wettability and the precipitation of asphaltene are the results of the reaction between crude oil and CO2. In the MF, asphaltene precipitates from the PL, while in the MT and SM, asphaltene precipitates both from the PL and PS. The amount of asphaltene precipitation strongly affects the E d in PS. The oil wettability increases more obviously with better pore-throat configurations. This study offers a reference and foundational understanding for evaluating CO2 displacement in tight sandstone reservoirs.

15.
Stroke ; 55(9): 2264-2273, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39114924

RESUMO

BACKGROUND: Cerebral small vessel disease (CSVD) is a group of neurological disorders that affect the small blood vessels within the brain, for which no effective treatments are currently available. We conducted a Mendelian randomization (MR) study to identify candidate therapeutic genes for CSVD. METHODS: We retrieved genome-wide association study data from 6 recently conducted, extensive investigations focusing on CSVD magnetic resonance imaging markers and performed a 2-sample MR analysis to assess the potential causal effects of gene expression and protein level within druggable genes on CSVD in blood and brain tissues. Colocalization analyses and repeat studies were undertaken to verify the relationship. Additionally, mediation analysis was conducted to explore the potential mechanisms involving druggable genes and known risk factors for CSVD. Finally, phenome-wide MR analyses were applied to evaluate the potential adverse effects related to the identified druggable genes for CSVD treatment. RESULTS: Overall, 5 druggable genes consistently showed associations with CSVD in MR analyses across both the discovery and validation cohorts. Notably, the ALDH2 and KLHL24 genes were identified as associated with CSVD in both blood and brain tissues, whereas the genes ADRB1, BTN3A2, and EFEMP1 were exclusively detected in brain tissue. Moreover, mediation analysis elucidated the proportion of the total effects mediated by CSVD risk factors through candidate druggable genes, which ranged from 5.5% to 18.5%, and offered potential explanations for the observed results. A comprehensive phenome-wide MR analysis further emphasized both the therapeutic benefits and potential side effects of targeting these candidate druggable genes. CONCLUSIONS: This study provides genetic evidence supporting the potential therapeutic benefits of targeting druggable genes for treating CSVD, which will be useful for prioritizing CSVD drug development.


Assuntos
Doenças de Pequenos Vasos Cerebrais , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Doenças de Pequenos Vasos Cerebrais/genética , Humanos , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem
16.
Thromb J ; 22(1): 73, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39118154

RESUMO

BACKGROUND: Exposure to a high-altitude environment is a risk factor for cerebral venous thrombosis (CVT) probably due to hypercoagulability. The study aims to explore the unique characteristics of CVT patients in high-altitude areas of China by comparing them with those in plain areas. METHODS: We retrospectively included consecutive patients with CVT admitted to Tibet Autonomous Region People's Hospital (altitude 3650 m) and Peking Union Medical College Hospital (altitude 43.5 m) between January 2015 and December 2023. Patients from the plateau and the plain were considered two independent groups in this study. The risk factors, clinical and radiological presentations, treatment, and outcomes were analyzed and compared between the two groups. RESULTS: A total of 169 patients with CVT were included in the study, 48 patients from plateau and 121 patients from plain. The median age was 27 and 34 years old, and women accounted for 66.7% and 54.5% respectively. Headache (91.7% vs. 71.1%, P = 0.004), altered consciousness (31.3% vs. 16.5%, P = 0.033), hemorrhage (41.7% vs. 19.0%, P = 0.002), and venous infarction (50.0% vs. 25.6%, P = 0.002) on imaging were more common in patients from plateau than those from plain. Pregnancy or puerperium was significantly more common in highland patients (25% vs. 5.8%, P < 0.001). The levels of D-Dimer (1.7 vs. 0.8 mg/L FEU, P = 0.01), fibrinogen (3.7 vs. 3.0 g/L, P < 0.001), hemoglobin (157 vs. 129 g/L, P = 0.01), white blood cells (9.6 vs. 7.5*1012/L, P < 0.001) and highly sensitive C-reactive protein (20.2 vs. 3.2 mg/L, P = 0.005) were remarkably higher in highland patients. The percentage of receiving anticoagulant therapy was lower in high-altitude patients (70.8% vs. 93.4%, P < 0.001). Favorable outcome at follow-up was observed in 81.4% of highland patients and 90.7% of lowland patients, with a median follow-up time of 330 days and 703 days respectively. CONCLUSIONS: The more severe clinical and imaging manifestations along with prominent inflammatory and hypercoagulable states were observed in plateau CVT patients, probably due to exposure to the hypoxic environment at high altitude. Pregnancy or puerperium were more common in highland patients. The overall prognosis of CVT patients from both groups were favorable.

17.
Sci Total Environ ; 951: 175759, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39182769

RESUMO

Biological treatment of food waste (FW) by black soldier fly larvae (BSFL) is considered as an effective management strategy. The composition and concentrations of nutrients in FW change during its storage and transport period, which potentially affect the FW conversion and BSFL growth. The present study systematically investigated the effect of different storage times (i.e., 0-15 d) on FW characteristics and its substantial influence on the BSFL growth. Results showed that the highest larvae weight of 282 mg and the shortest growth time of 14 days were achieved at the group of FW stored for 15 days, but shorter storage time (i.e., 2-7 d) had adverse effect on BSFL growth. Short storage time (i.e., 2-4 d) improved protein content of BSFL biomass and prolonged storage time (i.e., 7-10 d) led to the accumulation of fat content. The changes of substrate characteristics and indigenous microorganisms via FW storage time were the main reasons for BSFL growth difference. Lactic acid (LA) accumulation (i.e., 19.84 g/L) in FW storage for 7 days significantly limited the BSFL growth, leading to lowest larvae weight. Both the substrate and BSFL gut contained same bacterial communities (e.g., Klebsiella and Proteus), which exhibited similar change trend with the prolonged storage time. The transfer of Clostridioides from substrate to BSFL gut promoted nutrients digestion and intestinal flora balance with the FW stored for 15 days. Pathogens (e.g., Acinetobacter) in BSFL gut feeding with FW storage time of 7 days led to the decreased digestive function, consistent with the lowest larvae weight. Overall, shorter storage time (i.e., 2-7 d) inhibited the BSFL digestive function and growth performance, while the balance of the substrate nutrients and intestinal flora promoted the BSFL growth when using the FW stored for 15 days.


Assuntos
Microbioma Gastrointestinal , Larva , Valor Nutritivo , Animais , Larva/crescimento & desenvolvimento , Simuliidae/crescimento & desenvolvimento , Dípteros/crescimento & desenvolvimento , Perda e Desperdício de Alimentos
18.
Front Plant Sci ; 15: 1420649, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38947943

RESUMO

Introduction: Targeted herbicide application refers to precise application of herbicides in weed-infested areas according to the location and density of farmland weeds. At present, targeted herbicide application in wheat fields generally faces problems including the low herbicide adhesion rate, leading to omission and excessive loss of herbicides. Methods: To solve these problems, changes in the impact force of herbicide and the weed leaves in the operation process of a spraying system were studied from the interaction between weeds and herbicides applied. A dynamic model of weed leaves was established. On this basis, the research indicated that the herbicide adhesion rate is highest under spraying pressure of 0.4 MPa and flow rate of 0.011 kg/s when the spray height is 300 mm. To study the dynamic deformation of weed leaves and the distribution of liquid herbicides in the external flow field under weed-herbicide interaction, a dynamic simulation model of herbicide application was built using the finite element method. Results and Discussion: The results show that when the spray height is 300 mm, the maximum weed leaf deformation index (LDI) is 0.43 and the velocity in the external flow field is 0 m/s under spraying pressure of 0.4 MPa and flow rate of 0.011 kg/s. This finding indicates that the herbicide is not splashed elsewhere and the turbulence intensity in the weed area is 2%, implying steady flow of the herbicide, most of which can be retained on weed leaves. Field test results of application quality of the herbicide show that the maximum LDI is 0.41 and the coverage of the herbicide in the sheltered area below the leaves is 19.02% when the spraying pressure is 0.4 MPa, flow rate is 0.011 kg/s, and spray height is 300 mm. This solves the problem of a low rate of utilization of herbicides because the herbicide passes through weed plants, and achieves the precision herbicide application in wheat fields.

20.
Hum Brain Mapp ; 45(11): e26790, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39037119

RESUMO

Brain glymphatic dysfunction is critical in neurodegenerative processes. While animal studies have provided substantial insights, understandings in humans remains limited. Recent attention has focused on the non-invasive evaluation of brain glymphatic function. However, its association with brain parenchymal lesions in large-scale population remains under-investigated. In this cross-sectional analysis of 1030 participants (57.14 ± 9.34 years, 37.18% males) from the Shunyi cohort, we developed an automated pipeline to calculate diffusion-weighted image analysis along the perivascular space (ALPS), with a lower ALPS value indicating worse glymphatic function. The automated ALPS showed high consistency with the manual calculation of this index (ICC = 0.81, 95% CI: 0.662-0.898). We found that those with older age and male sex had lower automated ALPS values (ß = -0.051, SE = 0.004, p < .001, per 10 years, and ß = -0.036, SE = 0.008, p < .001, respectively). White matter hyperintensity (ß = -2.458, SE = 0.175, p < .001) and presence of lacunes (OR = 0.004, 95% CI < 0.002-0.016, p < .001) were significantly correlated with decreased ALPS. The brain parenchymal and hippocampal fractions were significantly associated with decreased ALPS (ß = 0.067, SE = 0.007, p < .001 and ß = 0.040, SE = 0.014, p = .006, respectively) independent of white matter hyperintensity. Our research implies that the automated ALPS index is potentially a valuable imaging marker for the glymphatic system, deepening our understanding of glymphatic dysfunction.


Assuntos
Imagem de Difusão por Ressonância Magnética , Sistema Glinfático , Humanos , Masculino , Feminino , Sistema Glinfático/diagnóstico por imagem , Sistema Glinfático/patologia , Sistema Glinfático/fisiopatologia , Pessoa de Meia-Idade , Estudos Transversais , Idoso , Imagem de Difusão por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Processamento de Imagem Assistida por Computador/métodos , Adulto , Estudos de Coortes
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