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How to predict animals' heat-avoidance behaviors is critical since behavior stands the first line for animals dealing with frequent heat events under ongoing climate warming. However, the discrepancy between the scarcity of research on heat-avoidance behaviors and the commonness of eco-physiological data for thermal tolerance and for thermal sensitivity such as the temperature-dependent survival time makes it difficult to link physiological thermal traits to heat-avoidance behavior. Aphids usually suck plant sap on a fixed site on the host plants at moderate temperatures, but they will leave and seek cooler feeding sites under stressful temperatures. Here we take the cereal aphid assemblages comprising different species with various development stages as a model system. We tested the hypotheses that heat tolerance (critical thermal maximum, CTmax) or heat sensitivity (temperature-dependent declining rate of survival time, similarly hereinafter) would associate with the temperature at which aphid activate heat-avoidance behavior. Specifically, we hypothesized the aphids with less heat tolerance or greater heat sensitivity would take a lower heat risk by leaving the host plant earlier. By mimicking the linear increase in ambient temperature during the daytime, we measured the CTmax and the heat-avoidance temperature (HAT, at which aphids leave the host plant to find cooler places) to understand their heat tolerance and heat-avoidance behavior. Then, we tested the survival time of aphids at different temperatures and calculated the slope of survival time declining with temperature to assess their heat sensitivity (HS). Finally, we examined the relationships between CTmax and HAT and between HS and HAT to understand if the heat-avoidance behavior associates with heat tolerance or with heat sensitivity. The results showed that HS and HAT had a strong correlation, with more heat sensitive individuals displayed lower HAT. By contrast, CTmax and HAT had a weak correlation. Our results thus provide evidence that heat sensitivity is a more reliable indicator than thermal tolerance linking with the heat-avoidance behavior in the aphid assemblages. Most existing studies use the indexes related to thermal tolerance to predict warming impacts. Our findings highlight the urgency to incorporate thermal sensitivity when predicting animal responses to climate change.
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Áfidos , Termotolerancia , Animales , Áfidos/fisiología , Reacción de Prevención , Calor , Conducta AnimalRESUMEN
Neuronal intranuclear inclusion disease (NIID) is a slowly progressing neurodegenerative disease characterized by eosinophilic intranuclear inclusions in the nervous system and multiple visceral organs. The clinical manifestation of NIID varies widely, and both familial and sporadic cases have been reported. Here we have performed genetic linkage analysis and mapped the disease locus to 1p13.3-q23.1; however, whole-exome sequencing revealed no potential disease-causing mutations. We then performed long-read genome sequencing and identified a large GGC repeat expansion within human-specific NOTCH2NLC. Expanded GGC repeats as the cause of NIID was further confirmed in an additional three NIID-affected families as well as five sporadic NIID-affected case subjects. Moreover, given the clinical heterogeneity of NIID, we examined the size of the GGC repeat among 456 families with a variety of neurological conditions with the known pathogenic genes excluded. Surprisingly, GGC repeat expansion was observed in two Alzheimer disease (AD)-affected families and three parkinsonism-affected families, implicating that the GGC repeat expansions in NOTCH2NLC could also contribute to the pathogenesis of both AD and PD. Therefore, we suggest defining a term NIID-related disorders (NIIDRD), which will include NIID and other related neurodegenerative diseases caused by the expanded GGC repeat within human-specific NOTCH2NLC.
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Cuerpos de Inclusión Intranucleares/patología , Enfermedades Neurodegenerativas/patología , Receptores Notch/genética , Expansión de Repetición de Trinucleótido/genética , Adulto , Anciano , Femenino , Humanos , Cuerpos de Inclusión Intranucleares/genética , Masculino , Persona de Mediana Edad , Enfermedades Neurodegenerativas/genética , Linaje , Secuenciación del ExomaRESUMEN
BACKGROUND: Oxidative stress is an important pathogenic factor in influenza A virus infection. It has been found that reactive oxygen species induced by the H9N2 influenza virus is associated with viral replication. However, the mechanisms involved remain to be elucidated. METHODS: In this study, the role of autophagy was investigated in H9N2 influenza virus-induced oxidative stress and viral replication in A549 cells. Autophagy induced by H9N2 was inhibited by an autophagy inhibitor or RNA interference, the autophagy level, viral replication and the presence of oxidative stress were detected by western blot, TCID50 assay, and Real-time PCR. Then autophagy and oxidative stress were regulated, and viral replication was determined. At last, the Akt/TSC2/mTOR signaling pathways was detected by western blot. RESULTS: Autophagy was induced by the H9N2 influenza virus and the inhibition of autophagy reduced the viral titer and the expression of nucleoprotein and matrix protein. The blockage of autophagy suppressed the H9N2 virus-induced increase in the presence of oxidative stress, as evidenced by decreased reactive oxygen species production and malonaldehyde generation, and increased superoxide dismutase 1 levels. The changes in the viral titer and NP mRNA level caused by the antioxidant, N-acetyl-cysteine (NAC), and the oxidizing agent, H2O2, confirmed the involvement of oxidative stress in the control of viral replication. NAC plus transfection with Atg5 siRNA significantly reduced the viral titer and oxidative stress compared with NAC treatment alone, which confirmed that autophagy was involved in the replication of H9N2 influenza virus by regulating oxidative stress. Our data also revealed that autophagy was induced by the H9N2 influenza virus through the Akt/TSC2/mTOR pathway. The activation of Akt or the inhibition of TSC2 suppressed the H9N2 virus-induced increase in the level of LC3-II, restored the decrease in the expression of phospho-pAkt, phospho-mTOR and phospho-pS6 caused by H9N2 infection, suppressed the H9N2-induced increase in the presence of oxidative stress, and resulted in a decrease in the viral titer. CONCLUSION: Autophagy is involved in H9N2 virus replication by regulating oxidative stress via the Akt/TSC2/mTOR signaling pathway. Thus, autophagy maybe a target which may be used to improve antiviral therapeutics.
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Células Epiteliales Alveolares/virología , Autofagia/genética , Regulación de la Expresión Génica , Subtipo H9N2 del Virus de la Influenza A/fisiología , Infecciones por Orthomyxoviridae/veterinaria , Estrés Oxidativo/genética , Replicación Viral , Células A549 , Animales , Humanos , Subtipo H9N2 del Virus de la Influenza A/patogenicidad , Transducción de Señal , PorcinosRESUMEN
Breast cancer has become the most common cancer for women in China.Lack of effective therapeutic targets,triple negative breast cancer(TNBC)has poorer prognosis compared with other subtypes of breast cancer.Tumor infiltrating lymphocytes(TILs)are a group of heterogeneous lymphocytes around the tumor,which are believed as immunoreactive products of host immune response to tumor antigens.At present,there have been reports on the predictive effect of TILs on the prognosis of breast cancer,and the available studies focus mainly on TNBC.This article briefly reviews the recent progress of tumor infiltrating lymphocytes in immunotherapy of TNBC.
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Neoplasias de la Mama Triple Negativas , Biomarcadores de Tumor , China , Femenino , Humanos , Inmunoterapia , Linfocitos Infiltrantes de Tumor , Pronóstico , Neoplasias de la Mama Triple Negativas/terapiaRESUMEN
BACKGROUND: The locus for familial cortical myoclonic tremor with epilepsy (FCMTE) has long been mapped to 8q24 in linkage studies, but the causative mutations remain unclear. Recently, expansions of intronic TTTCA and TTTTA repeat motifs within SAMD12 were found to be involved in the pathogenesis of FCMTE in Japanese pedigrees. We aim to identify the causative mutations of FCMTE in Chinese pedigrees. METHODS: We performed genetic linkage analysis by microsatellite markers in a five-generation Chinese pedigree with 55 members. We also used array-comparative genomic hybridisation (CGH) and next-generation sequencing (NGS) technologies (whole-exome sequencing, capture region deep sequencing and whole-genome sequencing) to identify the causative mutations in the disease locus. Recently, we used low-coverage (~10×) long-read genome sequencing (LRS) on the PacBio Sequel and Oxford Nanopore platforms to identify the causative mutations, and used repeat-primed PCR for validation of the repeat expansions. RESULTS: Linkage analysis mapped the disease locus to 8q23.3-24.23. Array-CGH and NGS failed to identify causative mutations in this locus. LRS identified the intronic TTTCA and TTTTA repeat expansions in SAMD12 as the causative mutations, thus corroborating the recently published results in Japanese pedigrees. CONCLUSIONS: We identified the pentanucleotide repeat expansion in SAMD12 as the causative mutation in Chinese FCMTE pedigrees. Our study also suggested that LRS is an effective tool for molecular diagnosis of genetic disorders, especially for neurological diseases that cannot be positively diagnosed by conventional clinical microarray and NGS technologies.
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Estudios de Asociación Genética , Intrones , Proteínas del Tejido Nervioso/genética , Linaje , Fenotipo , Secuencias Repetidas en Tándem , Adulto , Hibridación Genómica Comparativa , Epilepsias Mioclónicas/diagnóstico , Epilepsias Mioclónicas/genética , Femenino , Estudios de Asociación Genética/métodos , Humanos , Masculino , Análisis de Secuencia de ADN , Secuenciación del Exoma , Secuenciación Completa del GenomaRESUMEN
In this work, a sensitive and efficient method was established and validated for qualitative and quantitative analysis of major bioactive constituents in Dazhu Hongjingtian capsule by liquid chromatography tandem mass spectrometry. A total of 32 compounds were tentatively identified using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Furthermore, 12 constituents, namely gallic acid, 3,4-dihydroxybenzoic acid, salidroside, p-coumaric acid-4-O-ß-d-glucopyranoside, bergeninum, 4-hydroxybenzoic acid, 4-hydroxyphenylacetic acid, syringate, 6''-O-galloylsalidroside, rhodiosin, rhodionin and kaempferol-7-O-α-l-rhamnoside, were simultaneously quantified by the developed ultra-performance liquid chromatography coupled with a triple quadrupole mass spectrometry method in 9 min. All of them were analyzed on an Agilent ZorBax SB-C18 column (3.0 × 100 mm, 1.8 µm) with linear gradient elution of methanol-0.1% formic acid water. The proposed method was applied to analyze three batches of samples with acceptable linearity (R, 0.9979-0.9997), precision (RSD, 1.3-4.7%), repeatability (RSD, 1.7-4.9%), stability (RSD, 2.2-4.9%) and recovery (RSD, 0.6-4.4%) of the 12 compounds. As a result, the analytical method possessing high throughput and sensitivity is suitable for the quality control of Dazhu Hongjingtian capsule.
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Cromatografía Liquida/métodos , Medicamentos Herbarios Chinos/química , Espectrometría de Masas en Tándem/métodos , Estándares de Referencia , Reproducibilidad de los ResultadosRESUMEN
The extracting technology of salidroside, tyrosol, crenulatin and gallic acid from Rhodiolae Crenulatae Radix et Rhizoma was optimized. With extraction rate of salidroside, tyrosol, crenulatin and gallic acid as indexes, orthogonal test was used to evaluate effect of 4 factors on extracting technology, including concentration of solvent, the dosage of solvent, duration of extraction, and frequency of extraction. The results showed that, the best extracting technology was to extract in 70% alcohol with 8 times the weight of herbal medicine for 2 times, with 3 hours once. High extraction rate of salidroside, tyrosol, crenulatin and gallic acid were obtained with the present technology. The extracting technology was stable and feasible with high extraction rate of four compounds from Rhodiolae Crenulatae Radix et Rhizoma, it was suitable for industrial production.
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Fraccionamiento Químico/métodos , Química Farmacéutica/métodos , Cumarinas/aislamiento & purificación , Medicamentos Herbarios Chinos/aislamiento & purificación , Ácido Gálico/aislamiento & purificación , Glucósidos/aislamiento & purificación , Fenoles/aislamiento & purificación , Alcohol Feniletílico/análogos & derivados , Rizoma/química , Rhodiola/química , Alcohol Feniletílico/aislamiento & purificaciónRESUMEN
Tyrosol, crenulatin and salidroside are the main active constituents of Rhodiola crenulata, with extensive pharmacological activities. In the study, grams of high purity tyrosol, crenulatin and salidroside were simultaneously separated from R. crenulata by the first time. Firstly, R. crenulata was extracted by 70% alcohol. Then, with the yields of three compounds as the index, the macroporous resin was optimized. At last, grams of high purity tyrosol, crenulatin and salidroside were isolated by D-101 macroporousresin, purified by column chromatography. Detected by HPLC, the purity of three compounds were higher than 98%. This method has the advantages of simple process and operation, less dosage of organic solvent, highly yield and reproducibility, suitable for the simultaneously preparation of tyrosol, crenulatin and salidroside.
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Fraccionamiento Químico/métodos , Cumarinas/aislamiento & purificación , Medicamentos Herbarios Chinos/aislamiento & purificación , Glucósidos/aislamiento & purificación , Fenoles/aislamiento & purificación , Alcohol Feniletílico/análogos & derivados , Rhodiola/química , Química Farmacéutica , Cromatografía Líquida de Alta Presión , Cumarinas/análisis , Medicamentos Herbarios Chinos/análisis , Glucósidos/análisis , Fenoles/análisis , Alcohol Feniletílico/análisis , Alcohol Feniletílico/aislamiento & purificaciónRESUMEN
OBJECTIVE: To study the anti-complementary phenolic acids from Lonicera japonica. METHOD: The anti-complementary activity-directed isolation was carried out with the hemolysis test as guide. All isolation was evaluated for their in vitro anti-complementary activities. The structures were identified by various spectroscopic data including ESI-MS, 1H-NMR, 13C-NMR data. RESULT: Fourteen compounds were isolated from the EtOAc fraction of L. japonica extracts, including 8 phenolic acids: 5-O-caffeoylquinic acid (1), chlorogenic (2), 4-O-caffeoylquinic acid (3), 3,5-di-O-caffeoylquinic acid (4), 4,5-di-O-caffeoylquinic acid (5), 3,4-di-O-caffeoylquinic acid (6), caffeic acid (7) and methyl caffeate acid (8); 3 iridoids: secologanoside (9), sweroside (10) and secoxyloganin (11); and 3 flavonoids: luteolin (12), quercetin (13) and kaempferol (14). Compounds 1-9 and 11-14 showed anti-complementary activity in different extents and 3,5-di-O-caffeoylquinic acid (4) exhibited the most significant activity against the classical pathway. CONCLUSION: Compound 14 is obtained from this plant for the first time, phenolic acids are the main anti-complementary constituents of L. japonica and 3,5-di-O-caffeoylquinic acid(4) is a potential complement inhibitor with strong activity, which worthy to be studied further in the future.
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Inactivadores del Complemento/aislamiento & purificación , Hidroxibenzoatos/aislamiento & purificación , Lonicera/química , Inactivadores del Complemento/química , Inactivadores del Complemento/farmacología , Hidroxibenzoatos/química , Hidroxibenzoatos/farmacologíaRESUMEN
1,2,3,4,6-penta-O-galloyl-D-glucose (PGG) is one of the main active compounds of Guizhi Fuling capsule. Molecularly imprinted polymers (MIP) have high affinity toward template molecules synthesized by molecularly imprinted technology for its specific combined sites, which can overcome the shortcoming of traditional separation methods, such as complex operation, low efficiency, using large quantity of solvent and environmental pollution. In this paper, surface molecularly imprinted polymer (SMIP) was prepared by surface imprinting with PGG as the template molecule. Its adsorption capacity was measured by the scatchard equation. The separation of PGG from Guizhi Fuling capsule at preparatived scale was achieved with molecularly imprinted polymer as stationary phase and the purity was 90.2% by HPLC. This method can be used to prepare PGG from Guizhi Fuling capsule with large capacity and is easy to operate. It provides a new method for efficient separation and purification for other natural products.
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Medicamentos Herbarios Chinos/química , Taninos Hidrolizables/aislamiento & purificación , Polímeros/química , Adsorción , Cápsulas/química , Cromatografía Líquida de Alta Presión , Taninos Hidrolizables/química , Impresión Molecular , Polímeros/síntesis químicaRESUMEN
OBJECTIVE: To explore the effect of the hospital-community-home (HCH) linkage management mode in patients with type 2 diabetic nephropathy (DN). METHOD: A total of 80 patients with type 2 DN hospitalised in the Department of Nephrology of our hospital between July 2021 and June 2022 were recruited and subsequently divided into the observation group and the control group using the random number table method, with 40 patients in each group. The control group received routine health education and discharge guidance. The HCH linkage management model was implemented for the observation group based on routine care. The improvements in compliance behaviour, biochemical parameters of renal function, blood glucose level and self-management ability were compared before the intervention and at 3 and 6 months after the intervention. RESULTS: After the intervention, the scores for compliance behaviour of the observation group were better than those of the control group, with a statistically significant difference (P < 0.05). The biochemical indicators of renal function and blood glucose level were significantly lower in the observation group compared with in the control group, with a statistically significant difference (P < 0.05). After the intervention, the observation group showed a great improvement in self-management ability and cognition of the disease, with significant differences (P < 0.05). CONCLUSION: The HCH linkage management mode can improve the compliance behaviour of patients with type 2 DN, effectively improve the renal function and blood sugar level of patients, enhance the self-management ability and cognition of the disease and delay the development of the disease.
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Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Humanos , Nefropatías Diabéticas/terapia , Glucemia , Cooperación del Paciente , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/terapia , HospitalesRESUMEN
OBJECTIVE: Mammography is the principle imaging modality used for early diagnosis of breast cancer in Western countries. It has not been well-established whether this Western diagnostic modality is adoptable for Chinese women. The aim of this study was to evaluate the respective accuracy of the common diagnostic tools for breast cancer including history-taking, physical examination, ultrasound and mammography. METHODS: Clinical presentation and investigations for consecutive patients undergoing history-taking, physical examination, ultrasound, mammography and pathological assessment at Peking Union Medical College Hospital were prospectively recorded between April 2010 and September 2011. Breast cancer high-risk factors acquired by history-taking were input into the risk assessment model established previously by Eleventh Five Year Key Programs for Science and Technology Development of China (Grant No. 2006BAI02A09) and classified into low-, medium-, high- and extremely high-risk groups. The low- and medium-risk groups were defined as test negative, while the high- and extremely high-risk groups were defined as test positive. Each mammogram and ultrasound was reported prospectively using a five-point reporting scale of the American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS). Clinical data were compared with pathological findings. Sensitivity, specificity, positive predictive value (PRV), negative predictive value (NPV) and accuracy of respective diagnostic methods were calculated and compared. The patients were divided into two groups, above and below 50 years of age for subgroup analysis. RESULTS: A total of 1468 patients (1475 breast lesions) constituted the study population. The median age was 44 (range 13 - 92) years. Five hundred and fifty-one patients were diagnosed as breast cancer. The median age at diagnosis was 51 years and breast cancer peaked in the age group of 40 - 60 years. The sensitivity of risk assessment model, physical examination, ultrasound and mammogram was 47.5%, 86.2%, 89.8% and 79.3%, respectively; specificity was 68.8%, 83.3%, 81.0% and 88.7%, respectively; PRV was 47.6%, 75.5%, 73.8% and 80.8%, respectively; NPV was 68.8%, 91.0%, 93.0% and 87.8%, respectively; and accuracy was 60.9%, 84.4%, 84.3% and 85.2%, respectively. Further subgroup analysis demonstrated that age is an important factor influencing the sensitivity and specificity of physical examination, ultrasound and mammography. CONCLUSIONS: Ultrasound is more sensitive than mammography for early diagnosis of breast cancer in Chinese women and should be routinely used as a first-line diagnostic tool. Only a single diagnostic method is not enough sometimes and combined examination is needed for some high-risk populations.
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Neoplasias de la Mama/diagnóstico , Carcinoma Ductal de Mama/diagnóstico , Detección Precoz del Cáncer/métodos , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Enfermedades de la Mama/diagnóstico , Enfermedades de la Mama/diagnóstico por imagen , Neoplasias de la Mama/diagnóstico por imagen , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/diagnóstico por imagen , Carcinoma Ductal de Mama/diagnóstico por imagen , China , Femenino , Humanos , Mamografía , Anamnesis , Persona de Mediana Edad , Examen Físico , Estudios Prospectivos , Medición de Riesgo , Sensibilidad y Especificidad , Ultrasonografía Mamaria , Adulto JovenRESUMEN
To explore the association of polymorphism in the serotonin transporter gene and the susceptibility to alcohol dependence in Yunnan Han population, PCR and DNA sequencing techniques were used to detect 5-HTT-linked promoter region (5-HTTLPR). One hundred and eighteen alcohol dependent patients as case group and 214 normal people as control group were employed in this study. Significant differences in genotype frequencies were present between case group and control group of 5-HTTLPR (P<0.05). The proportion of L/L and L/S genotype was significantly smaller in case group than that was in control group (OR=0.581, P=0.026). No significant association was observed in allelic frequencies, which differed in different ethnic groups. In conclusion, 5-HTTLPR polymorphism may be associated with alcohol dependent patients, and the genotype L/L or L/S may be a genetic factor that is responsible for decreasing susceptibility of alcohol dependence in Yunnan Han population.
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Alcoholismo/genética , Predisposición Genética a la Enfermedad , Polimorfismo Genético , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genética , Adulto , Anciano , China/etnología , Humanos , Persona de Mediana Edad , Regiones Promotoras GenéticasRESUMEN
BACKGROUND: Hypertensive intracerebral hemorrhage is a common critical disease of the nervous system, comprising one fifth of all acute cerebrovascular diseases and has a high disability and mortality rate. It severely affects the patients' quality of life. AIM: To analyze the short-term effect and long-term prognosis of neuroendoscopic minimally invasive surgery for hypertensive intracerebral hemorrhage. METHODS: From March 2018 to May 2020, 118 patients with hypertensive intracerebral hemorrhage were enrolled in our study and divided into a control group and observation group according to the surgical plan. The control group used a hard-channel minimally invasive puncture and drainage procedure. The observation group underwent minimally invasive neuroendoscopic surgery. The changes in the levels of serum P substances (SP), inflammatory factors [tumor necrosis factor-α, interleukin-6 (IL-6), IL-10], and the National Hospital Stroke Scale (NIHSS) and Barthel index scores were recorded. Surgery related indicators and prognosis were compared between the two groups. RESULTS: The operation time (105.26 ± 28.35) of the observation group was min longer than that of the control group, and the volume of intraoperative bleeding was 45.36 ± 10.17 mL more than that of the control group. The hematoma clearance rates were 88.58% ± 4.69% and 94.47% ± 4.02% higher than those of the control group at 48 h and 72 h, respectively. Good prognosis rate (86.44%) was higher in the observation group than in the control group, and complication rate (5.08%) was not significantly different from that of the control group (P > 0.05).The SP level and Barthel index score of the two groups increased (P < 0.05) and the inflammatory factors and NIHSS score decreased (P < 0.05). The cytokine levels, NIHSS score, and Barthel index score were better in the observation group than in the control group (P < 0.05). CONCLUSION: Neuroendoscopic minimally invasive surgery is more complicated than hard channel minimally invasive puncture drainage in the treatment of hypertensive intracerebral hemorrhage; however, hematoma clearance is more thorough, and the short-term effect and long-term prognosis are better than hard channel minimally invasive puncture drainage.
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Animal studies implicate meningeal lymphatic dysfunction in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease (PD). However, there is no direct evidence in humans to support this role1-5. In this study, we used dynamic contrast-enhanced magnetic resonance imaging to assess meningeal lymphatic flow in cognitively normal controls and patients with idiopathic PD (iPD) or atypical Parkinsonian (AP) disorders. We found that patients with iPD exhibited significantly reduced flow through the meningeal lymphatic vessels (mLVs) along the superior sagittal sinus and sigmoid sinus, as well as a notable delay in deep cervical lymph node perfusion, compared to patients with AP. There was no significant difference in the size (cross-sectional area) of mLVs in patients with iPD or AP versus controls. In mice injected with α-synuclein (α-syn) preformed fibrils, we showed that the emergence of α-syn pathology was followed by delayed meningeal lymphatic drainage, loss of tight junctions among meningeal lymphatic endothelial cells and increased inflammation of the meninges. Finally, blocking flow through the mLVs in mice treated with α-syn preformed fibrils increased α-syn pathology and exacerbated motor and memory deficits. These results suggest that meningeal lymphatic drainage dysfunction aggravates α-syn pathology and contributes to the progression of PD.
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Drenaje , Vasos Linfáticos/fisiopatología , Meninges/fisiopatología , Enfermedad de Parkinson/fisiopatología , Progresión de la Enfermedad , Humanos , Imagen por Resonancia Magnética , Meninges/diagnóstico por imagen , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/terapia , alfa-Sinucleína/metabolismoRESUMEN
Due to the refractory and partial sensitive treatments to malignant cancers, immunotherapy has increasingly become a hotspot in effective anti-tumor research. However, at present, existing animal models could not accurately describe the interaction between human tissue and tumor cells for preclinical trials. Furthermore, it is a tough obstacle to reconstitute the immune system and microenvironment in a mouse model identical to humans due to species differences. In the establishment of the humanized mouse model, the co-transplantation of human immunocytes with/without tissues and tumor cells is the key breakthrough to solve this problem. The compelling progress has been investigated in the preclinical drug test for diverse tumor types. This review mainly summarized the development of immunodeficient mice, and the construction and practicability of the humanized mouse model. Furthermore, the investigators also highlight the pros and cons, and recent progress in immunotherapy research for advanced utility of human cancer diseases.
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H9N2 avian influenza viruses (AIVs) can cross species barriers and expand from birds tomammals and humans. It usually leads to economic loss for breeding farms and poses a serious threat to human health.This study investigated the molecular characteristics of H9N2 AIV isolated from a racing pigeon and its pathogenesis in BALB/c mice and pigeons. Phylogenetic analysis indicated that the H9N2 virus belonged to the Ck/BJ/94-like lineage, and acquired multiple specific amino acid substitutions that might contribute to viral transmission from birds to mammals and humans. A pathogenesis study showed that both mice and pigeons infected with H9N2 virus showed clinical signs and mortality. The H9N2 viruses efficiently replicated in mice and pigeons. In our study, high levels of viral shedding were detected in pigeons, but the infection was not transmitted to co-housed pigeons. Histopathological examination revealed the presence of inflammatory responses in the infected mice and pigeons. Immunohistochemical analysis showed the presence of H9N2 virus in multiple organs of the infected mice and pigeons. Moreover, the infected mice and pigeons demonstrated significant cytokine/chemokine production. Our results showed that the H9N2 virus can infect mice and pigeons, and can not be transmitted between pigeons through direct contact.
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Columbidae/virología , Genoma Viral , Subtipo H9N2 del Virus de la Influenza A/genética , Subtipo H9N2 del Virus de la Influenza A/patogenicidad , Gripe Aviar/virología , Sustitución de Aminoácidos , Animales , Quimiocinas/inmunología , Citocinas/inmunología , Femenino , Subtipo H9N2 del Virus de la Influenza A/aislamiento & purificación , Gripe Aviar/transmisión , Ratones , Ratones Endogámicos BALB C , Mutación , Filogenia , Organismos Libres de Patógenos Específicos , Replicación Viral , Esparcimiento de VirusRESUMEN
α-Synucleinopathies are characterized by autonomic dysfunction and motor impairments. In the pure autonomic failure (PAF), α-synuclein (α-Syn) pathology is confined within the autonomic nervous system with no motor features, but mouse models recapitulating PAF without motor dysfunction are lacking. Here, we show that in TgM83+/- mice, inoculation of α-Syn preformed fibrils (PFFs) into the stellate and celiac ganglia induces spreading of α-Syn pathology only through the autonomic pathway to both the central nervous system (CNS) and the autonomic innervation of peripheral organs bidirectionally. In parallel, the mice develop autonomic dysfunction, featured by orthostatic hypotension, constipation, hypohidrosis and hyposmia, without motor dysfunction. Thus, we have generated a mouse model of pure autonomic dysfunction caused by α-Syn pathology. This model may help define the mechanistic link between transmission of pathological α-Syn and the cardinal features of autonomic dysfunction in α-synucleinopathy.
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Ganglios Autónomos/fisiopatología , Insuficiencia Autonómica Pura/patología , Sinucleinopatías/patología , alfa-Sinucleína/metabolismo , Animales , Técnicas de Observación Conductual , Modelos Animales de Enfermedad , Ganglios Autónomos/patología , Humanos , Masculino , Ratones , Ratones Transgénicos , Mutación , Agregado de Proteínas , Insuficiencia Autonómica Pura/genética , Insuficiencia Autonómica Pura/fisiopatología , Sinucleinopatías/genética , Sinucleinopatías/fisiopatología , alfa-Sinucleína/administración & dosificación , alfa-Sinucleína/genéticaRESUMEN
Influenza A virus usually leads to economic loss to breeding farms and pose a serious threat to human health. Virus infecting tissues directly and influenza virus-induced excessive production of inflammatory factors play the key role in pathogenesis of the disease, but the mechanism is not well clarified. Here, the role of autophagy was investigated in H9N2 influenza virus-triggered inflammation. The results showed that autophagy was induced by H9N2 virus in A549 cells and in mice. Inhibiting autophagy by an autophagy inhibitor (3-methyladenine, 3-MA) or knockdown of Atg5(autophagy-related gene) by Atg5 siRNA significantly suppressed H9N2 virus replication, H9N2 virus-triggered inflammatory cytokines and chemokines, including IL-1ß, TNF-α, IL-8, and CCL5 in vitro and in vivo, and suppressed H9N2 virus-triggered acute lung injury as indicated as accumulative mortality of mice, inflammatory cellular infiltrate and interstitial edema, thickening of the alveolar walls in mice lung tissues, increased inflammatory cytokines and chemokines, increased W/D ratio in mice. Moreover, autophagy mediated inflammatory responses through Akt-mTOR, NF-κB and MAPKs signaling pathways. Our data showed that autophagy was essential in H9N2 influenza virus-triggered inflammatory responses, and autophagy could be target to treat influenza virus-caused lung inflammation.
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Lesión Pulmonar Aguda/inmunología , Proteína 5 Relacionada con la Autofagia/metabolismo , Autofagia/genética , Subtipo H9N2 del Virus de la Influenza A/fisiología , Gripe Humana/inmunología , Infecciones por Orthomyxoviridae/inmunología , Células A549 , Animales , Proteína 5 Relacionada con la Autofagia/genética , Citocinas/metabolismo , Humanos , Mediadores de Inflamación/metabolismo , Ratones , Ratones Endogámicos BALB C , ARN Interferente Pequeño/genética , Transducción de SeñalRESUMEN
We have demonstrated a novel way to form thickness-controllable polyelectrolyte-film/nanoparticle patterns by using a plasma etching technique to form, first, a patterned self-assembled monolayer surface, followed by layer-by-layer assembly of polyelectrolyte-films/nanoparticles. Octadecyltrimethoxysilane (ODS) and (3-aminopropyl)triethoxysilane (APTES) self-assembled monolayers (SAMs) were used for polyelectrolyte-film and nanoparticle patterning, respectively. The resolution of the proposed patterning method can easily reach approximately 2.5â µm. The height of the groove structure was tunable from approximately 2.5 to 150â nm. The suspended lipid membrane across the grooves was fabricated by incubating the patterned polyelectrolyte groove arrays in solutions of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) giant unilamellar vesicles (GUVs). The method demonstrated here reveals a new path to create patterned 2D or 3D structures.