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BACKGROUND: Arterial remodeling is a common pathophysiological change in the pathogenesis of cardiovascular diseases in which the phenotypic switch of vascular smooth muscle cells (VSMC) plays an important role. Recently, an increasing number of long non-coding RNAs(lncRNAs) have been shown to encode micropeptides that play biological roles and have great clinical transformation potential. However, the role of micropeptides encoded by lncRNAs in arterial remodeling has not been well studied and requires further exploration. METHODS AND RESULTS: Through bioinformatic analysis and experimental verification, we found that a new lncRNA, the mitochondrial function-related lncRNA (MFRL), encodes a 64-amino acid micropeptide, MFRLP. MFRL and MFRLP play important roles in the phenotypic switch of VSMC. Further experiments showed that MFRLP interacts with mitochondrial cytochrome b to reduce accumulation of reactive oxygen species, suppress mitophagy and inhibit the VSMC switch from contractile to synthetic phenotype. CONCLUSIONS: LncRNA MFRL encodes the micropeptide MFRLP, which interacts with mitochondrial cytochrome b to inhibit the VSMC switch from contractile to synthetic phenotype and improve arterial remodeling.
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BACKGROUND: Reportedly, the stress-hyperglycemia ratio (SHR) is closely associated with poor prognosis in patients with severe acute disease. However, the community-dwelling may also be in a state of stress due to environmental exposure. Our study aimed to explore the association between SHR and all-cause mortality in the community-dwelling population. METHODS: A total of 18 480 participants were included out of 82 091 from the NHANES 1999-2014 survey. The Kaplan-Meier survival analyses were used to assess the disparities in survival rates based on SHR, and the log-rank test was employed to investigate the distinctions between groups. The multivariate Cox regression analysis and restricted cubic spline (RCS) analysis were performed to assess the association of SHR with all-cause mortality. A subgroup analysis was also conducted. RESULTS: A total of 3188 deaths occurred during a median follow-up period of 11.0 (7.7; 15.4) years. The highest risk for all-cause mortality was observed when SHR≤ 0.843 or SHR ≥0.986 (log-rank p < .001). After adjusting for the confounding factors, compared with subjects in the second SHR quartile (Q2), participants in the highest (Q4, adjusted hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.28-1.73) and lowest quartiles (Q1, adjusted HR 1.37, 95% CI 1.16-1.60) have a higher probability of all-cause death. The RCS observed a dose-response U-shaped association between SHR and all-cause mortality. The U-shaped association between SHR and all-cause mortality was similar across subgroup analysis. CONCLUSIONS: The SHR was significantly associated with all-cause mortality in the community-dwelling population, and the relationship was U-shaped.
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Hiperglicemia , Vida Independente , Inquéritos Nutricionais , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Vida Independente/estatística & dados numéricos , Hiperglicemia/mortalidade , Hiperglicemia/sangue , Hiperglicemia/epidemiologia , Adulto , Idoso , Causas de Morte , Fatores de Risco , Mortalidade/tendências , Estresse Fisiológico , Estados Unidos/epidemiologia , Prognóstico , Estimativa de Kaplan-MeierRESUMO
A new species group of Lilioceris Reitter, 1913 is proposed and reviewed, the semipunctata group. It includes eleven species: L.atrilateralis Kimoto & Takizawa, 1973, L.consentanea (Lacordaire, 1845), L.dentifemoralis Long, 1988, L.discrepens (Baly, 1879), L.jianfenglingensis Long, 1988, L.latissima (Pic, 1932), L.lianzhouensis Long, 2000a, L.rondoni Kimoto & Gressitt, 1979, L.rufometallica (Pic, 1923), L.semipunctata (Fabricius, 1801), and L.yuae Long, 2000b. Liliocerisdiscrepens and L.rondoni were new records from China. Two synonyms are proposed: Liliocerisxinglongensis Long, 1988, syn. nov. of L.consentanea (Lacordaire, 1845), and Criocerisrufimembris Pic, 1921, syn. nov. of L.semipunctata. An identification key, descriptions, habitus photographs, geographic distributions, host plants and habitats (if available), are provided for these species.
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A negative correlation exists between attention and pain. The cognitive impairments linked to pain can significantly impede a patient's healing process and everyday tasks, particularly for individuals experiencing persistent pain. Furthermore, it has been demonstrated that diversion can effectively decrease pain levels in individuals. The focus of this review is to analyze clinical trials and fundamental investigations regarding alterations in focus and persistent discomfort. Moreover, we investigated the common neuroanatomy associated with attention and pain. Furthermore, we examined the impact of various neuromodulators on the transmission of pain and processes related to attention, while also considering the potential neural mechanisms that contribute to the co-occurrence of pain and attention deficits. Further investigation in this field will enhance our comprehension of patient symptoms and the underlying pathophysiology, ultimately resulting in more objective approaches to treatment.
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Brain extraction is an important prerequisite for the automated diagnosis of intracranial lesions and determines, to a certain extent, the accuracy of subsequent lesion identification, localization, and segmentation. To address the problem that the current traditional image segmentation methods are fast in extraction but poor in robustness, while the Full Convolutional Neural Network (FCN) is robust and accurate but relatively slow in extraction, this paper proposes an adaptive mask-based brain extraction method, namely AMBBEM, to achieve brain extraction better. The method first uses threshold segmentation, median filtering, and closed operations for segmentation, generates a mask for the first time, then combines the ResNet50 model, region growing algorithm, and image properties analysis to further segment the mask, and finally complete brain extraction by multiplying the original image and the mask. The algorithm was tested on 22 test sets containing different lesions, and the results showed MPA = 0.9963, MIoU = 0.9924, and MBF = 0.9914, which were equivalent to the extraction effect of the Deeplabv3+ model. However, the method can complete brain extraction of approximately 6.16 head CT images in 1 second, much faster than Deeplabv3+, U-net, and SegNet models. In summary, this method can achieve accurate brain extraction from head CT images more quickly, creating good conditions for subsequent brain volume measurement and feature extraction of intracranial lesions.
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Encéfalo , Cabeça , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Redes Neurais de Computação , Algoritmos , Processamento de Imagem Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodosRESUMO
Objective: To evaluate the prognostic value of the systemic immune-inflammatory index (SII) for predicting in-hospital major adverse cardiovascular events (MACEs) in patients with acute myocardial infarction (AMI) and establish a relevant nomogram. Methods: This study included 954 AMI patients. We examined three inflammatory factors (SII, platelet to lymphocyte ratio (PLR) and neutrophil to lymphocyte ratio (NLR)) to see which one predicts in-hospital MACEs better. The predictors were subsequently screened using bidirectional stepwise regression method, and a MACE nomogram was constructed via logistic regression analysis. The predictive value of the model was evaluated using the area under the curve (AUC), sensitivity and specificity. In addition, the clinical utility of the nomogram was evaluated using decision curve analysis. We also compared the nomogram with the Global Registry of Acute Coronary Events (GRACE) scoring system. Results: 334 (35.0%) patients had MACEs. The SII (AUC =0.684) had a greater predictive value for in-hospital MACEs in AMI patients than the PLR (AUC =0.597, P<0.001) or NLR (AUC=0.654, P=0.01). The area under the curve (AUC) of the SII-based multivariable model for predicting MACEs, which was based on the SII, Killip classification, left ventricular ejection fraction, age, urea nitrogen (BUN) concentration and electrocardiogram-based diagnosis, was 0.862 (95% CI: 0.833-0.891). Decision curve and calibration curve analysis revealed that SII-based multivariable model demonstrated a good fit and calibration and provided positive net benefits than the model without SII. The predictive value of the SII-based multivariable model was greater than that of the GRACE scoring system (P<0.001). Conclusion: SII is a promising, reliable biomarker for identifying AMI patients at high risk of in-hospital MACEs, and SII-based multivariable model may serve as a quick and easy tool to identify these patients.
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The Chinese species of Lilioceris are revised, and three new species are described from Tibet, China: Lilioceriszhentangensis Xu & Liang, sp. nov., Liliocerismedogensis Xu & Liang, sp. nov. and Lilioceriszayuensis Xu & Liang, sp. nov. Five species of Lilioceris are reported for China as new records: L.dromedarius (Baly, 1861), L.pulchella (Baly, 1859), L.semicostata (Jacoby, 1908), L.unicolor (Hope, 1831) and L.nepalensis Takizawa, 1989. Liliocerisseminigra (Jacoby, 1889) is proposed as a junior synonym of L.unicolor Hope, 1831. Redescriptions, habitus photographs, geographic distributions, host plants (if available) and habitats are provided for these species.
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Baculoviridae, a virus family characterized by a single large double stranded DNA, encompasses the majority of viral bioinsecticides, representing a highly promising and environmentally friendly pesticide approach to insect control. This study focuses on the characterization of a baculovirus isolated from larvae of Calliteara abietis (Erebidae, Lymantriidae) collected in Mongolian pinaceae forests. This new isolate was called Calliteara abietis nucleopolyhedrovirus (CaabNPV). CaabNPV exhibits an irregular polyhedron shape, and significant variation in the diameter of its occlusion bodies (OBs) was observed. Nucleotide distance calculations confirmed CaabNPV as a novel baculovirus. The CaabNPV genome spans 177,161 bp with a G+C content of 45.12% and harbors 150 potential open reading frames (ORFs), including 38 core genes. A comprehensive genomic analysis categorizes CaabNPV within Group II alphabaculovirus, revealing a close phylogenetic relationship with Alphabaculovirus orleucostigmae (OrleNPV). Additionally, repeat sequence analysis identified three highly repetitive sequences consisting of 112 bp repeat units, known as homologous regions (hrs). This research contributes valuable insights into CaabNPV's phylogenetic placement, genomic structure, and its potential applications in insect biocontrol.
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Mariposas , Nucleopoliedrovírus , Animais , Baculoviridae/genética , Filogenia , Genoma Viral , Análise de Sequência de DNA , Fases de Leitura AbertaRESUMO
AIMS: The lack of effective pharmacotherapies for aortic aneurysms (AA) is a persistent clinical challenge. Lipid metabolism plays an essential role in AA. However, the impact of lipid-lowering drugs on AA remains controversial. The study aimed to investigate the genetic association between lipid-lowering drugs and AA. METHODS AND RESULTS: Our research used publicly available data on genome-wide association studies (GWASs) and expression quantitative trait loci (eQTL) studies. Genetic instruments, specifically eQTLs related to drug-target genes and SNPs (single nucleotide polymorphisms) located near or within the drug-target loci associated with low-density lipoprotein cholesterol (LDL-C), have been served as proxies for lipid-lowering medications. Drug-Target Mendelian Randomization (MR) study is used to determine the causal association between lipid-lowering drugs and different types of AA. The MR analysis revealed that higher expression of HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase) was associated with increased risk of AA (OR = 1.58, 95% CI = 1.20-2.09, P = 1.20 × 10-03) and larger lumen size (aortic maximum area: OR = 1.28, 95% CI = 1.13-1.46, P = 1.48 × 10-04; aortic minimum area: OR = 1.26, 95% CI = 1.21-1.42, P = 1.78 × 10-04). PCSK9 (proprotein convertase subtilisin/kexin type 9) and CETP (cholesteryl ester transfer protein) show a suggestive relationship with AA (PCSK9: OR = 1.34, 95% CI = 1.10-1.63, P = 3.07 × 10-03; CETP: OR = 1.38, 95% CI = 1.06-1.80, P = 1.47 × 10-02). No evidence to support genetically mediated NPC1L1 (Niemann-Pick C1-Like 1) and LDLR (low-density lipoprotein cholesterol receptor) are associated with AA. CONCLUSION: This study provides causal evidence for the genetic association between lipid-lowering drugs and AA. Higher gene expression of HMGCR, PCSK9, and CETP increases AA risk. Furthermore, HMGCR inhibitors may link with smaller aortic lumen size.
KEY FINDINGS: High expression of HMGCR, PCSK9, and CETP was positively correlated with the risk of aortic aneurysms, highlighting that the corresponding lipid-lowering drugs may be preferred for preventing arterial aneurysms in high-risk individuals with dyslipidemia. We found that genetically predicted HMGCR inhibitors were positively associated with smaller aortic lumen size, which is the first time to support the causal association of gene HMGCR on the lumen size of aortic aneurysms.
This Mendelian randomization study used publicly available data involving over 1 million individuals to demonstrate the causal relationship between five target genes of LDL-C-lowering medicines and the risk of aortic aneurysms, and implied one lipid-lowering drug may link with the lumen size of aortic aneurysms.
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Proteínas de Transferência de Ésteres de Colesterol , Estudo de Associação Genômica Ampla , Hidroximetilglutaril-CoA Redutases , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Pró-Proteína Convertase 9 , Humanos , Proteínas de Transferência de Ésteres de Colesterol/genética , Pró-Proteína Convertase 9/genética , Hidroximetilglutaril-CoA Redutases/genética , Aneurisma Aórtico/genética , Aneurisma Aórtico/epidemiologia , Locos de Características Quantitativas , Hipolipemiantes/uso terapêutico , Fatores de Risco , Predisposição Genética para Doença , Medição de Risco , Fenótipo , Dislipidemias/genética , Dislipidemias/tratamento farmacológico , Dislipidemias/sangue , Dislipidemias/epidemiologia , Receptores de LDL/genética , Variantes Farmacogenômicos , LDL-Colesterol/sangue , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêuticoRESUMO
Insect legs play a crucial role in various modes of locomotion, including walking, jumping, swimming, and other forms of movement. The flexibility of their leg joints is critical in enabling various modes of locomotion. The frog-legged leaf beetle Sagra femorata possesses remarkably enlarged hind legs, which are considered to be a critical adaptation that enables the species to withstand external pressures. When confronted with external threats, S. femorata initiates a stress response by rapidly rotating its hind legs backward and upward to a specific angle, thereby potentially intimidating potential assailants. Based on video analysis, we identified 4 distinct phases of the hind leg rotation process in S. femorata, which were determined by the range of rotation angles (0°-168.77°). Utilizing micro-computed tomography (micro-CT) technology, we performed a 3-dimensional (3D) reconstruction and conducted relative positioning and volumetric analysis of the metacoxa and metatrochanter of S. femorata. Our analysis revealed that the metacoxa-trochanter joint is a "screw-nut" structure connected by 4 muscles, which regulate the rotation of the legs. Further testing using a 3D-printed model of the metacoxa-trochanter joint demonstrated its possession of a self-locking mechanism capable of securing the legs in specific positions to prevent excessive rotation and dislocation. It can be envisioned that this self-locking mechanism holds potential for application in bio-inspired robotics.
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Inflammation is a crucial pathophysiological mechanism in atherosclerosis (AS). This study aims to investigate the impact of sulfotransferase family 2b member 1 (SULT2B1) on the inflammatory response of macrophages and the progression of AS. Here, we reported that SULT2B1 expression increased with the progression of AS. In AS model mice, knockdown of Sult2b1 led to remission of AS and reduced inflammation levels. Further exploration of the downstream molecular mechanisms of SULT2B1 revealed that suppressing Sult2b1 in macrophages resulted in decreased levels of 25HC3S in the nucleus, elevated expression of Lxr, and increased the transcription of Lncgga3-204. In vivo, knockdown of Lncgga3-204 aggravated the inflammatory response and AS progression, while the simultaneous knockdown of both Sult2b1 and Lncgga3-204 exacerbated AS and the inflammatory response compared with knockdown of Sult2b1 alone. Increased binding of Lncgga3-204 to SMAD4 in response to oxidized-low density lipoprotein (ox-LDL) stimulation facilitated SMAD4 entry into the nucleus and regulated Smad7 transcription, which elevated SMAD7 expression, suppressed NF-κB entry into the nucleus, and ultimately attenuated the macrophage inflammatory response. Finally, we identified the presence of a single nucleotide polymorphism (SNP), rs2665580, in the SULT2B1 promoter region in monocytes from coronary artery disease (CAD) patients. The predominant GG/AG/AA genotypes were observed in the Asian population. Elevated SULT2B1 expression in monocytes with GG corresponded to elevated inflammatory factor levels and more unstable coronary plaques. To summarize, our study demonstrated that the critical role of SULT2B1/Lncgga3-204/SMAD4/NF-κB in AS progression. SULT2B1 serves as a novel biomarker indicating inflammatory status, thereby offering insights into potential therapeutic strategies for AS.
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Aterosclerose , Progressão da Doença , Inflamação , Macrófagos , Proteína Smad4 , Sulfotransferases , Aterosclerose/metabolismo , Aterosclerose/genética , Aterosclerose/patologia , Sulfotransferases/genética , Sulfotransferases/metabolismo , Animais , Camundongos , Macrófagos/metabolismo , Humanos , Inflamação/metabolismo , Inflamação/patologia , Proteína Smad4/metabolismo , Proteína Smad4/genética , Masculino , Camundongos Endogâmicos C57BL , FemininoRESUMO
BACKGROUND: Visceral adiposity index (VAI) and lipid accumulation product (LAP) are comprehensive indicators to evaluate visceral fat and determine the metabolic health of individuals. Carotenoids are a group of naturally occurring antioxidants associated with several diseases. The purpose of this investigation was to explore the association between serum carotenoid concentration and VAI or LAP. METHODS: The data were obtained from the National Health and Nutrition Examination Survey between 2001 and 2006. The levels of serum carotenoids were evaluated using high-performance liquid chromatography. Multivariate linear regression models were employed to investigate the relationship between levels of serum carotenoids and VAI or LAP. The potential non-linear relationship was determined using threshold effect analysis and fitted smoothing curves. Stratification analysis was performed to investigate the potential modifying factors. RESULTS: In total, 5,084 participants were included in this population-based investigation. In the multivariate linear regressions, compared to the lowest quartiles of serum carotenoids, the highest quartiles were significantly associated with VAI, and the effect size (ß) and 95% CI was - 0.98 (- 1.34, - 0.62) for α-carotene, - 1.39 (- 1.77, - 1.00) for ß-carotene, - 0.79 (- 1.18, - 0.41) for ß-cryptoxanthin, - 0.68 (- 0.96, - 0.39) for lutein/zeaxanthin, and - 0.88 (- 1.50, - 0.27) for trans-lycopene. Using piece-wise linear regression models, non-linear relationships were found between ß-carotene and trans-lycopene and VAI with an inflection point of 2.44 (log2-transformed, ug/dL) and 3.80 (log2-transformed, ug/dL), respectively. The results indicated that α-carotene, ß-cryptoxanthin, and lutein/zeaxanthin were linearly associated with VAI. An inverse association was also found between serum carotenoids and LAP after complete adjustments. CONCLUSION: This study revealed that several serum carotenoids were associated with VAI or LAP among the general American population. Further large prospective investigations are warranted to support this finding.
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Produto da Acumulação Lipídica , beta Caroteno , Humanos , Licopeno , Inquéritos Nutricionais , Estudos Transversais , Luteína , Zeaxantinas , beta-Criptoxantina , Adiposidade , Estudos Prospectivos , CarotenoidesRESUMO
BACKGROUND: Brain extraction is an essential prerequisite for the automated diagnosis of intracranial lesions and determines, to a certain extent, the accuracy of subsequent lesion recognition, location, and segmentation. Segmentation using a fully convolutional neural network (FCN) yields high accuracy but a relatively slow extraction speed. METHODS: This paper proposes an integrated algorithm, FABEM, to address the above issues. This method first uses threshold segmentation, closed operation, convolutional neural network (CNN), and image filling to generate a specific mask. Then, it detects the number of connected regions of the mask. If the number of connected regions equals 1, the extraction is done by directly multiplying with the original image. Otherwise, the mask was further segmented using the region growth method for original images with single-region brain distribution. Conversely, for images with multi-region brain distribution, Deeplabv3 + is used to adjust the mask. Finally, the mask is multiplied with the original image to complete the extraction. RESULTS: The algorithm and 5 FCN models were tested on 24 datasets containing different lesions, and the algorithm's performance showed MPA = 0.9968, MIoU = 0.9936, and MBF = 0.9963, comparable to the Deeplabv3+. Still, its extraction speed is much faster than the Deeplabv3+. It can complete the brain extraction of a head CT image in about 0.43 s, about 3.8 times that of the Deeplabv3+. CONCLUSION: Thus, this method can achieve accurate brain extraction from head CT images faster, creating a good basis for subsequent brain volume measurement and feature extraction of intracranial lesions.
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Algoritmos , Encéfalo , Humanos , Encéfalo/diagnóstico por imagem , Redes Neurais de Computação , Tomografia Computadorizada por Raios XRESUMO
Toll-like receptors (TLRs) recognize altered gut microbiota triggering an immune response. These responses play a critical role in the pathogenesis and treatment of inflammatory bowel disease (IBD). IBD is characterized by inflammation of the intestinal tracts as in Crohn's disease and ulcerative colitis. However, one challenge in determining the role of a specific TLR in IBD and its underlying mechanism is disparity. Variance in age, gender, race, and ethnicity shows a dramatic difference in the disease incidence, severity, and response to treatment. Delineating the role of TLRs in IBD relies on both a knockout mouse and a disease model. Here, we describe a detailed protocol on how to use nearly identical genetic backgrounds of TLR wild-type and knockout littermate mice in a dextran sodium sulfate (DSS)-induced colitis model.
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Colite Ulcerativa , Colite , Doença de Crohn , Doenças Inflamatórias Intestinais , Animais , Camundongos , Doenças Inflamatórias Intestinais/genética , Receptores Toll-Like/genética , Camundongos KnockoutRESUMO
The present contribution revises the genus Parena Motschulsky, 1860, a group of arboreal carabid beetles with 46 recognized species, distributed in Tropical Asia, Sub-Saharan Africa, and the north and east coastal Australasia. We re-evaluate the infrageneric taxonomy of the genus and redefine three subgenera: Parena s. str., Bothynoptera Schaum, 1863 and Crossoglossa Chaudoir, 1872, based on the morphological characters of external features, male genitalia and female ovipositors. Under these three subgenera, we define 14 species groups to contain all known species. Keys for the identification of all subgenera, species groups, and species are provided, along with diagnostic characters, included species, geographical distribution, brief discussion on monophyly and relationships for each subgenus and species group, ample species descriptions, distribution maps, habitus images, and genitalia illustrations. The previous alpha-taxonomy of the genus Parena is defective, and several species were described without genital morphological comparisons with their real adelphotaxon. Based on careful examination of a large amount of type materials, we propose 19 new synonyms: P. rufotestacea Jedlicka, 1934, as a junior synonym of P. cavipennis (Bates, 1873); P. perforata (Bates, 1873), P. nepalensis Kirschenhofer, 1994, and P. kunmingensis Kirschenhofer, 1996, as junior synonyms of P. dorsigera (Schaum, 1863); P. wrasei Kirschenhofer, 2006, as a junior synonym of P. kurosai Habu, 1967; P. nantouensis Kirschenhofer, 1996 and P. kataevi Kirschenhofer, 2006, as junior synonyms of P. tesari (Jedlicka, 1951); P. yunnana Kirschenhofer, 1994, as a junior synonym of P. shapingensis Xie & Yu, 1993; P. albomaculata Habu, 1979, as a junior synonym of P. malaisei (Andrewes, 1947); P. koreana Kirschenhofer, 1994, as a junior synonym of P. monostigma (Bates, 1873); P. phongsalyensis Kirschenhofer, 2011, as a junior synonym of P. quadrisignata Mateu, 1977; P. sellata (Heller, 1921), P. hastata (Heller, 1921), P. sellatoides (Jedlicka, 1940), P. fasciata var. unicolor Louwerens, 1949, and P. sumatrana Kirschenhofer, 2011, as junior synonyms of P. fasciata (Chaudoir, 1872); P. nigrolineata nipponensis Habu, 1964 and P. schillhammeri Kirschenhofer, 2006, as junior synonyms of P. nigrolineata (Chaudoir, 1852); and P. alluaudi Jeannel, 1949, as a junior synonym of P. madagascariensis (Alluaud, 1917). Furthermore, the specific status of P. scutata (Alluaud, 1917) is resurrected from synonym with P. plagiata Motschulsky, 1864. Parena sticta (Andrewes, 1947) is excluded from Parena and a new combination is suggested: Peliocypas stictus (Andrewes, 1947) comb. nov. A total of eight new species are described: P. (Crossoglossa) sciakyi sp. nov. (type locality: Guadalcanal, Solomon Islands), P. (Bothynoptera) heteronycha sp. nov. (type locality: Houaphan, Laos), P. (Bothynoptera) emarginata sp. nov. (type locality: Muli, Sichuan, China), P. (Bothynoptera) gonggaica sp. nov. (type locality: Hailuogou, Sichuan, China), P. (Bothynoptera) triguttata sp. nov. (type locality: Kangding, Sichuan, China), P. (Parena) picipes sp. nov. (type locality: Trus Madi, Borneo), P. (Parena) fulva sp. nov. (type locality: Dodoma, Tanzania), and P. (Parena) ruficornis sp. nov. (type locality: Lobaye, the Central African Republic). Several of these new species are very rare in collections, with four of them known from females only.
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Besouros , Masculino , Feminino , Animais , TanzâniaRESUMO
Ferroptosis, a newly identified iron-dependent form of cell death, has recently been implicated in the pathogenesis of Parkinson's disease (PD). Dl-3-n-butylphthalide (NBP) attenuates behavioral and cognitive deficits in animal models of PD. However, the potential of NBP to prevent dopaminergic neuron death by suppressing ferroptosis has rarely been explored. In this study, we aimed to investigate the effects of NBP on ferroptosis in erastin-induced dopaminergic neurons (MES23.5 cells) and the underlying mechanisms involved in these effects. Our results demonstrated that erastin significantly decreased viability of MES23.5 dopaminergic neurons in a dose-dependent manner, which was reversible by ferroptosis inhibitors. We further verified that NBP protected erastin-treated MES23.5 cells from death by inhibiting ferroptosis. Erastin increased the mitochondrial membrane density, caused lipid peroxidation, and decreased GPX4 expression in MES23.5 cells, which could be reversed by NBP preconditioning. NBP pretreatment suppressed erastin-induced labile iron accumulation and reactive oxygen species generation. Moreover, we demonstrated that erastin significantly reduced FTH expression, and pre-administration with NBP promoted Nrf2 translocation into the nucleus and increased the protein level of FTH. Additionally, the expression of LC3B-II in MES23.5 cells pretreated with NBP before administration of erastin was lower than that in cells treated with erastin alone. NBP reduced colocalization of FTH and autophagosomes in MES23.5 cells exposed to erastin. Finally, erastin gradually inhibited NCOA4 expression in a time-dependent manner, which was reversible by NBP pretreatment. Taken together, these results indicated that NBP suppressed ferroptosis via regulating FTH expression, which was achieved by promoting Nrf2 nuclear translocation and inhibiting NCOA4-mediated ferritinophagy. As such, NBP may be a promising therapeutic agent for the treatment of neurological diseases associated with ferroptosis.
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Ferroptose , Animais , Neurônios Dopaminérgicos/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Ferro/metabolismoRESUMO
OBJECTIVES: Blood flow into the side branch affects the calculation of coronary angiography-derived fractional flow reserve (FFR), called Angio-FFR. Neglecting or improperly compensating for the side branch flow may decrease the diagnostic accuracy of Angio-FFR. This study aims to evaluate the diagnostic accuracy of a novel Angio-FFR analysis that considers the side branch flow based on the bifurcation fractal law. METHODS: A one-dimensional reduced-order model based on the vessel segment was used to perform Angio-FFR analysis. The main epicardial coronary artery was divided into several segments according to the bifurcation nodes. Side branch flow was quantified using the bifurcation fractal law to correct the blood flow in each vessel segment. In order to verify the diagnostic performance of our Angio-FFR analysis, two other computational methods were taken as control groups: (i) FFR_s: FFR calculated by delineating the coronary artery tree to consider side branch flow, (ii) FFR_n: FFR calculated by just delineating the main epicardial coronary artery and neglecting the side branch flow. RESULTS: The analysis of 159 vessels from 119 patients showed that our Anio-FFR calculation method had comparable diagnostic accuracy to FFR_s and provided significantly higher diagnostic accuracy than that of FFR_n. In addition, using invasive FFR as a reference, the Pearson correlation coefficients of Angio-FFR and FFRs were 0.92 and 0.91, respectively, while that of FFR_n was only 0.85. CONCLUSIONS: Our Angio-FFR analysis has demonstrated good diagnostic performance in assessing the hemodynamic significance of coronary stenosis by using the bifurcation fractal law to compensate for side branch flow. CLINICAL RELEVANCE STATEMENT: Bifurcation fractal law can be used to compensate for side branch flow during the Angio-FFR calculation of the main epicardial vessel. Compensating for side branch flow can improve the ability of Angio-FFR to diagnose stenosis functional severity. KEY POINTS: ⢠The bifurcation fractal law could accurately estimate the blood flow from the proximal main vessel into the main branch, thus compensating for the side branch flow. ⢠Angiography-derived FFR based on the bifurcation fractal law is feasible to evaluate the target diseased coronary artery without delineating the side branch.
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Doença da Artéria Coronariana , Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico , Humanos , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Fractais , Angiografia Coronária/métodos , Hemodinâmica , Vasos Coronários/diagnóstico por imagem , Índice de Gravidade de Doença , Valor Preditivo dos TestesRESUMO
Cationic tuning for lanthanide (Ce3+/Pr3+)-activated inorganic phosphors with stable, efficient, and fast-decay 5d-4f emissions has emerged as an important strategy toward the continuing pursuit of superior scintillators. The in-depth understanding of the cationic effects on photo- and radioluminescence of lanthanides Ce3+ and Pr3+ centers is requisite for the rational cationic tuning. Here, we perform a systematic study on the structure and photo- and X-ray radioluminescence properties of K3RE(PO4)2:Ce3+/Pr3+ (RE = La, Gd, and Y) phosphors to elucidate the underlying cationic effects on their 4f-5d luminescence. By using the Rietveld refinements, low-temperature synchrotron-radiation vacuum ultraviolet-ultraviolet spectra, vibronic coupling analyses, and vacuum-referred binding energy schemes, the origins of lattice parameter evolutions, 5d excitation energies, 5d emission energies, and Stokes shifts as well as good emission thermal stabilities of K3RE(PO4)2:Ce3+ systems are revealed. In addition, the correlations of Pr3+ luminescence to Ce3+ in the same sites are also discussed. Finally, the X-ray excited luminescence manifests that the K3Gd(PO4)2:1%Ce3+ sample possesses a light yield of â¼10,217 photons/MeV, indicating its potentiality toward X-ray detection application. These results deepen the understanding of cationic effects on Ce3+ and Pr3+ 4f-5d luminescence and inspire the inorganic scintillator development.
RESUMO
BACKGROUND: Toll-like receptors (TLRs) are the key sensors of innate immunity for triggering immune responses against infections. TLRs are well known to be expressed and activated in innate immune cells, such as macrophage and dendritic cells, but we and others have found that some TLRs are also functional in epithelial cells. However, the role of an epithelial TLR in prostate cancer remains elusive. METHODS: TLR5 expression in messenger RNA and protein level in prostate cancer was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC). The activation of TLR5 signaling in epithelial cells was detected upon nuclear factor-κB activation by luciferase assay and western blot analysis, and proinflammatory cytokine activation by RT-qPCR. Distinguishing between the TLR5 and NLRC4 pathways, both recognizing flagellin, is determined by small interfering RNA and proinflammatory cytokine activation. The role of TLR5 in prostate cancer was analyzed by IHC and bioinformatics using a general and single-cell database. RESULTS: In the present study, we show that TLR5, among other TLRs, is exceedingly expressed in human prostate cancer cells. This cancer epithelial cell TLR5 functions to activate the TLR5 signaling pathway in human prostate cancer cells, as it does with innate immune cell TLR5. The bacterial protein flagellin induces a robust immune response in prostate cancer cells in a TLR5-dependent but NLRC4-independent manner. TLR5 is highly expressed in prostate cancer patient specimens, and high TLR5 expression in prostate cancer patients indicates a favorable prognosis. CONCLUSIONS: TLR5, as an innate immunity receptor, is a functional TLR in human prostate cancer epithelial cells. TLR5 plays an important role in prostate cancer development and is a new potential prognosis biomarker. TLR5 may represent a novel immunotherapy target against prostate cancer.
Assuntos
Neoplasias da Próstata , Receptor 5 Toll-Like , Masculino , Humanos , Receptor 5 Toll-Like/genética , Receptor 5 Toll-Like/metabolismo , Flagelina/genética , Flagelina/metabolismo , Regulação para Cima , Receptores Toll-Like/genética , Citocinas/metabolismo , Neoplasias da Próstata/genética , PrognósticoRESUMO
Atherosclerosis is one of the most common types of cardiovascular disease and is driven by lipid accumulation and chronic inflammation in the arteries, which leads to stenosis and thrombosis. Researchers have been working to design multifunctional nanomedicines with the ability to target, diagnose, and treat atherosclerosis, but recent studies have also identified that nanomaterials can cause atherosclerosis. Therefore, this review aims to outline the molecular mechanisms and physicochemical properties of nanomaterials that promote atherosclerosis. By analyzing the toxicological effects of nanomaterials on cells involved in the pathogenesis of atherosclerosis such as vascular endothelial cells, vascular smooth muscle cells and immune cells, we aim to provide new perspectives for the prevention and treatment of atherosclerosis, and raise awareness of nanotoxicology to advance the clinical translation and sustainable development of nanomaterials.