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In China, most SARS-CoV-2-infected individuals had been vaccinated with inactivated vaccines. However, little is known about their immune resistances to the previous variants of concerns (VOCs) and the current Omicron sublineages. Here, we collected convalescent serum samples from SARS-CoV-2-infected individuals during the ancestral, Delta, and Omicron BA.1 waves, and evaluated their cross-neutralizing antibodies (nAbs) against the previous VOCs and the current Omicron sublineages using VSV-based pseudoviruses. In the convalescents who had been unvaccinated and vaccinated with two doses of inactivated vaccines, we found infections from either the ancestral or the Delta strain elicited moderate cross-nAbs to previous VOCs, but very few cross-nAbs to the Omicron sublineages, including BA.1, BA.2, BA.3, and BA.4/5. The individuals who had been vaccinated with two doses of inactivated vaccines before Omicron BA.1 infection had moderate nAbs to Omicron BA.1, but weak cross-nAbs to the other Omicron sublineages. While three doses of inactivated vaccines followed Omicron BA.1 infection induced elevated and still weak cross-nAbs to other Omicron sublineages. Our results indicate that the Omicron sublineages show significant immune escape in the previously SARS-CoV-2-infected individuals and thus highlights the importance of vaccine boosters in this population.
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COVID-19 , SARS-CoV-2 , Humanos , Vacunas de Productos Inactivados , Sueroterapia para COVID-19 , Anticuerpos Neutralizantes , Anticuerpos AntiviralesRESUMEN
High-order assemblies of amelogenin, the major protein in enamel protein matrix, are believed to act as the template for enamel mineral formation. The Leucine-rich amelogenin (LRAP) is a natural splice-variant of amelogenin, a functional protein in vivo, containing conserved domains of amelogenin. In this work, we showed LRAP aggregates hierarchically into assemblies with various sizes including scattered beads, beads-on-a-string and gel-like precipitations in the presence of both calcium and phosphate ions. Solid-state NMR combined with X-ray diffraction and microscopic techniques, was applied to give a picture of LRAP self-assemblies at the atomic level. Our results, for the first time, confirmed LRAP assemblies with different sizes all contained a consistent rigid segment with ß-sheet secondary structure (residues 12-27) and the ß-sheet segment would further assemble into amyloid-like structures.
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Amelogenina/química , Proteínas Amiloidogénicas/química , Leucina/química , Espectroscopía de Resonancia Magnética/métodos , Proteínas Recombinantes/química , Amelogenina/genética , Amelogenina/metabolismo , Proteínas Amiloidogénicas/genética , Proteínas Amiloidogénicas/metabolismo , Animales , Calcio/química , Calcio/metabolismo , Concentración de Iones de Hidrógeno , Leucina/metabolismo , Ratones , Microscopía de Fuerza Atómica , Microscopía Electrónica de Transmisión , Fosfatos/química , Fosfatos/metabolismo , Estructura Secundaria de Proteína , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/ultraestructura , Difracción de Rayos X/métodosRESUMEN
OBJECTIVES: There is conflicting data regarding the response of older people with HIV (PWH) to antiretroviral therapy (ART). The objective of this study was to evaluate the long-term immunological and virological responses, changes in regimen, and adverse drug reactions (ADRs) in older participants (50+ years) compared with younger (18-34âyears) and middle-aged (35-49âyears) PWH. METHODS: A retrospective review of medical records was conducted on 1622 participants who received ART in Yunnan Province, China, from 2010 to 2019. The study compared CD4+ T-cell counts, CD4+/CD8+ ratio, and relative numbers between different groups using the Kruskal-Wallis test. Cox proportional hazards regression models were used to identify variables associated with the occurrence of immune reconstitution insufficiency. The rates of immune reconstitution, incidence of ADRs, and rates of treatment change were analyzed using the chi-squared test or Fisher's exact test. RESULTS: Over 95% achieved viral load 200âcopies/ml or less, with no age-related difference. However, older participants exhibited significantly lower CD4+ T-cell counts and CD4+/CD8+ recovery post-ART (Pâ<â0.001), with only 32.21% achieving immune reconstitution (compared with young: 52.16%, middle-aged: 39.29%, Pâ<â0.001) at the end of follow-up. Middle-aged and elderly participants changed ART regimens more because of ADRs, especially bone marrow suppression and renal dysfunction. CONCLUSION: Although the virological response was consistent across age groups, older individuals showed poorer immune responses and higher susceptibility to side effects. This underscores the need for tailored interventions and comprehensive management for older patients with HIV.
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Fármacos Anti-VIH , Infecciones por VIH , Persona de Mediana Edad , Anciano , Humanos , Infecciones por VIH/tratamiento farmacológico , Fármacos Anti-VIH/efectos adversos , China , Resultado del Tratamiento , Recuento de Linfocito CD4 , Carga ViralRESUMEN
HIV-1CRF08_BC is the most prevalent epidemic subtype among heterosexual (HET) and intravenous drug users (IDUs) in Kunming, Yunnan. Using the pol region of gene sequences derived from molecular epidemiological surveys, we developed a molecular transmission network for the purpose of analyzing its epidemiological characteristics, assessing its epidemiological trends, identifying its potential transmission relationships, and developing targeted interventions. HyPhy 2.2.4 was used to calculate pairwise genetic distances between sequences; GraphPad-Prism 8.0 was employed to determine the standard genetic distance; and Cytoscope 3.7.2 was applied to visualize the network. We used the network analysis tools to investigate network characteristics and the Molecular Complex Detection (MCODE) tool to observe the growth of the network. We utilized a logistic regression model to examine the factors influencing clustering and a zero-inflated Poisson model to investigate the factors influencing potential transmission links. At the standard genetic distance threshold of 0.008, 406 out of 858 study participants were clustered in 132 dissemination networks with a total network linkage of 868, and the number of links per sequence ranged from 1 to 19. The MCODE analysis identified three significant modular clusters in the networks, with network scores ranging from 4.9 to 7. In models of logistic regression, HET, middle-aged and elderly individuals, and residents of northern and southeastern Kunming were more likely to enter the transmission network. According to the zero-inflated Poisson model, age, transmission category, sampling year, marital status, and CD4+ T level had a significant effect on the size of links. The molecular clusters in Kunming's molecular transmission network are specific and aggregate to a certain extent. HIV-1 molecular network analysis provided information on local transmission characteristics, and these findings helped to determine the priority of transmission-reduction interventions.
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OBJECTIVE: To investigate genomic variations of two Chinese Yersinia pestis isolates that were isolated from different plague foci obtained from vaccine strain EV76 from the Yunnan province of China. METHODS: A microarray containing 12 000 probes covering the entire genome of seven Yersinia pestis and two Yersinia pseudotuberculosis strains, was used. PCR assays were performed to confirm microarray results. RESULTS: The gene variations detected included the absence of five genes related to the synthesis of betaine in both EV76 and another sequenced attenuated strain, KIM D27. Several genes related to phage-related membrane proteins were found to be absent in the Antiqua biovar Yunnan strain, 485, which was isolated from a rodent plague foci. CONCLUSION: These findings provide initial insight into the distinct strains isolated from natural foci, within their genomic context, including Yunnan Y. pestis strains. This information will be used therefore to establish subsequent comparisons of these sequences with published complete genomes of other strains.
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Hibridación Genómica Comparativa/métodos , Yersinia pestis/genética , China , Genoma Bacteriano/genética , Reacción en Cadena de la PolimerasaRESUMEN
The killing effect of different concentrations of garlic extract solution on Schistosoma japonicum cercariae and Oncomelania snails was observed under dissecting microscope. Mice were infected by cercariae through the abdominal skin daubed by garlic solution or by deionized water as control. The results showed that the cercariae were killed in (77.33 +/- 25.01) s in average, it needed (73.00 +/- 1.73)- (299.67 +/- 18.96) s under the garlic solution concentrations of 50.00%-0.79% respectively, while the cercariae kept alive in 600 s in the control. The snails were killed in 1 d by 100% garlic solution but no death in the control in 2 d. No mouse daubed with different concentrations of garlic solution was found infected by schistosomes while 100% of the control mice got infected. It is concluded that the garlic shows satisfactory effect in killing cercariae and Oncomelania snails, and may prevent schistosome infection by daubing the skin.
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Cercarias/efectos de los fármacos , Ajo/química , Extractos Vegetales/farmacología , Schistosoma japonicum/efectos de los fármacos , Caracoles/efectos de los fármacos , Animales , Ratones , Esquistosomiasis JapónicaRESUMEN
BACKGROUND: Yunnan has the highest rates of HIV in China. Other treatable sexually transmitted infections (STIs) are associated with accelerated HIV transmission and poor ART outcomes, but are only diagnosed by syndromic algorithms. METHODS: We recruited 406 HIV-positive participants for a cross-sectional study (204 ART-naive and 202 receiving ART). Blood samples and first-voided urine samples were collected. Real-time polymerase chain reaction methods were used for diagnosing Chlamydia trachomatis (CT), Neisseria gonorrhea (NG) and Mycoplasma genitalium (MG). Syphilis and herpes simplex virus type 2 (HSV-2) tests were also performed. RESULTS: Among the 406 participants, the overall prevalence of STIs was 47.0% and 45.1% in ART-naive individuals and 49.0% in individuals receiving ART, respectively. The testing frequencies were 11.6% (11.8% vs. 11.4%), 33.2% (29.4% vs. 37.1%), 3.2% (3.4% vs. 3.0%), 2.0% (3.4% vs. 0.5%) and 4.7% (6.4% vs. 3.0%) for active syphilis, HSV-2, CT, NG and MG, respectively. The percentage of multiple infections in both groups was 10.8% (22/204) in ART-naive participants and 9.9% (20/202) in participants receiving ART. Female sex, an age between 18 and 35 years, ever injecting drugs, homosexual or bisexual status, HIV/HBV coinfection, and not receiving ART were identified as risk factors. Self-reported asymptomatic patients were not eliminated from having a laboratory-diagnosed STI. CONCLUSIONS: The STI prevalence was 47.0% (45.1% vs. 49.0%), and HSV-2, syphilis and MG were the most common STIs in HIV-infected individuals. We found a high prevalence (6.4%) of MG in ART-naive individuals. HIV-positive individuals tend to neglect or hide their genital tract discomfort; thus, we suggest strengthening STI joint screening and treatment services among HIV-infected individuals regardless of whether they describe genital tract discomfort.
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Infecciones por VIH/epidemiología , Tamizaje Masivo/métodos , Medición de Riesgo/métodos , Enfermedades de Transmisión Sexual/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , China/epidemiología , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
Latent reservoir persistence remains a major obstacle for curing human immunodeficiency virus type 1 (HIV-1) infection. Thus, strategies for the elimination of latent HIV-1 are urgently needed. As a bromodomain and extra-terminal (BET) inhibitor, BMS-986158 has been used in clinical trials for advanced solid tumors and hematological malignancies. Here, we found that BMS-986158 reactivated latent HIV-1 in three types of HIV-1 latency cells in vitro, and in combination antiretroviral therapy (cART)-treated patient-derived peripheral blood mononuclear cells ex vivo, without influencing global immune cell activation. BMS-986158 reactivated latent HIV-1 by increasing phosphorylation of CDK9 at Thr186 and promoting recruitment of CDK9 and RNA polymerase II to the HIV-1 long terminal repeat in J-Lat cells. Furthermore, BMS-986158 exerted strong synergism in reactivating latent HIV-1 when combined with prostratin and vorinostat and enhanced the antiviral activity of anti-HIV-1 drugs. Finally, BMS-986158 showed antiviral activity in an HIV-1 acute infection model, possibly by arresting the cell cycle in infected cells. Thus, these results suggest that BMS-986158 is a potential candidate for AIDS/HIV-1 therapy.
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The continuously arising of SARS-CoV-2 variants has been posting a great threat to public health safety globally, from B.1.17 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.617.2 (Delta) to B.1.1.529 (Omicron). The emerging or re-emerging of the SARS-CoV-2 variants of concern is calling for the constant monitoring of their epidemics, pathogenicity and immune escape. In this study, we aimed to characterize replication and pathogenicity of the Alpha and Delta variant strains isolated from patients infected in Laos. The amino acid mutations within the spike fragment of the isolates were determined via sequencing. The more efficient replication of the Alpha and Delta isolates was documented than the prototyped SARS-CoV-2 in Calu-3 and Caco-2 âcells, while such features were not observed in Huh-7, Vero E6 and HPA-3 âcells. We utilized both animal models of human ACE2 (hACE2) transgenic mice and hamsters to evaluate the pathogenesis of the isolates. The Alpha and Delta can replicate well in multiple organs and cause moderate to severe lung pathology in these animals. In conclusion, the spike protein of the isolated Alpha and Delta variant strains was characterized, and the replication and pathogenicity of the strains in the cells and animal models were also evaluated.
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COVID-19 , SARS-CoV-2 , Animales , Cricetinae , Humanos , Ratones , Enzima Convertidora de Angiotensina 2 , Células CACO-2 , COVID-19/virología , Ratones Transgénicos , SARS-CoV-2/patogenicidad , Glicoproteína de la Espiga del Coronavirus , VirulenciaRESUMEN
The emerging SARS-CoV-2 variants, commonly with many mutations in S1 subunit of spike (S) protein are weakening the efficacy of the current vaccines and antibody therapeutics. This calls for the variant-proof SARS-CoV-2 vaccines targeting the more conserved regions in S protein. Here, we designed a recombinant subunit vaccine, HR121, targeting the conserved HR1 domain in S2 subunit of S protein. HR121 consisting of HR1-linker1-HR2-linker2-HR1, is conformationally and functionally analogous to the HR1 domain present in the fusion intermediate conformation of S2 subunit. Immunization with HR121 in rabbits and rhesus macaques elicited highly potent cross-neutralizing antibodies against SARS-CoV-2 and its variants, particularly Omicron sublineages. Vaccination with HR121 achieved near-full protections against prototype SARS-CoV-2 infection in hACE2 transgenic mice, Syrian golden hamsters and rhesus macaques, and effective protection against Omicron BA.2 infection in Syrian golden hamsters. This study demonstrates that HR121 is a promising candidate of variant-proof SARS-CoV-2 vaccine with a novel conserved target in the S2 subunit for application against current and future SARS-CoV-2 variants.
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Vacunas contra la COVID-19 , COVID-19 , Animales , Cricetinae , Ratones , Humanos , Conejos , SARS-CoV-2 , Macaca mulatta , Mesocricetus , Glicoproteína de la Espiga del Coronavirus/genética , COVID-19/prevención & control , Anticuerpos Neutralizantes , Ratones Transgénicos , Anticuerpos AntiviralesRESUMEN
The succinate-acetate permease (SatP) is an anion channel with six transmembrane domains. It forms different oligomers, especially hexamers in the detergent as well as in the membrane. Solid-state NMR studies of SatP were carried out successfully on SatP complexes by reconstructing the protein into liposomes or retaining the protein in the native membrane of E. coli., where it was expressed. The comparison of 13C-13C 2D correlation spectra between the two samples showed great similarity, opening the possibility to further study the acetate transport mechanism of SatP in its native membrane environment. Solid-state NMR studies also revealed small chemical shift differences of SatP in the two different membrane systems, indicating the importance of the lipid environment in determining the membrane protein structures and dynamics. Combining different 2D SSNMR spectra, chemical shift assignments were made on some sites, consistent with the helical structures in the transmembrane domains. In the end, we pointed out the limitation in the sensitivity for membrane proteins with such a size, and also indicated possible ways to overcome it.
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RIPK3 amyloid complex plays crucial roles during TNF-induced necroptosis and in response to immune defense in both human and mouse. Here, we have structurally characterized mouse RIPK3 homogeneous self-assembly using solid-state NMR, revealing a well-ordered N-shaped amyloid core structure featured with 3 parallel in-register ß-sheets. This structure differs from previously published human RIPK1/RIPK3 hetero-amyloid complex structure, which adopted a serpentine fold. Functional studies indicate both RIPK1-RIPK3 binding and RIPK3 amyloid formation are essential but not sufficient for TNF-induced necroptosis. The structural integrity of RIPK3 fibril with three ß-strands is necessary for signaling. Molecular dynamics simulations with a mouse RIPK1/RIPK3 model indicate that the hetero-amyloid is less stable when adopting the RIPK3 fibril conformation, suggesting a structural transformation of RIPK3 from RIPK1-RIPK3 binding to RIPK3 amyloid formation. This structural transformation would provide the missing link connecting RIPK1-RIPK3 binding to RIPK3 homo-oligomer formation in the signal transduction.
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Amiloide/metabolismo , Amiloide/ultraestructura , Necroptosis/fisiología , Proteína Serina-Treonina Quinasas de Interacción con Receptores/química , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Animales , Benzotiazoles , Supervivencia Celular , Drosophila , Herpesviridae , Humanos , Ratones , Simulación de Dinámica Molecular , Necroptosis/genética , Conformación Proteica , Ratas , Proteína Serina-Treonina Quinasas de Interacción con Receptores/genética , Alineación de Secuencia , Análisis de Secuencia de Proteína , Transducción de SeñalRESUMEN
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) continue to impact countries worldwide. At present, inadequate diagnosis and unreliable evaluation systems hinder the implementation and development of effective prevention and treatment strategies. Here, we conducted a horizontal and longitudinal study comparing the detection rates of SARS-CoV-2 nucleic acid in different types of samples collected from COVID-19 patients and SARS-CoV-2-infected monkeys. We also detected anti-SARS-CoV-2 antibodies in the above clinical and animal model samples to identify a reliable approach for the accurate diagnosis of SARS-CoV-2 infection. Results showed that, regardless of clinical symptoms, the highest detection levels of viral nucleic acid were found in sputum and tracheal brush samples, resulting in a high and stable diagnosis rate. Anti-SARS-CoV-2 immunoglobulin M (IgM) and G (IgG) antibodies were not detected in 6.90% of COVID-19 patients. Furthermore, integration of nucleic acid detection results from the various sample types did not improve the diagnosis rate. Moreover, dynamic changes in SARS-CoV-2 viral load were more obvious in sputum and tracheal brushes than in nasal and throat swabs. Thus, SARS-CoV-2 nucleic acid detection in sputum and tracheal brushes was the least affected by infection route, disease progression, and individual differences. Therefore, SARS-CoV-2 nucleic acid detection using lower respiratory tract samples alone is reliable for COVID-19 diagnosis and study.
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Prueba de COVID-19/veterinaria , COVID-19/diagnóstico , SARS-CoV-2/genética , Animales , Anticuerpos Antivirales , Modelos Animales de Enfermedad , Haplorrinos , Humanos , Estudios Longitudinales , Faringe/virología , Valor Predictivo de las Pruebas , SARS-CoV-2/inmunología , Manejo de Especímenes , Esputo/virologíaRESUMEN
Understanding the processes of immune regulation in patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial for improving treatment. Here, we performed longitudinal whole-transcriptome RNA sequencing on peripheral blood mononuclear cell (PBMC) samples from 18 patients with coronavirus disease 2019 (COVID-19) during their treatment, convalescence, and rehabilitation. After analyzing the regulatory networks of differentially expressed messenger RNAs (mRNAs), microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) between the different clinical stages, we found that humoral immunity and type I interferon response were significantly downregulated, while robust T-cell activation and differentiation at the whole transcriptome level constituted the main events that occurred during recovery from COVID-19. The formation of this T cell immune response might be driven by the activation of activating protein-1 (AP-1) related signaling pathway and was weakly affected by other clinical features. These findings uncovered the dynamic pattern of immune responses and indicated the key role of T cell immunity in the creation of immune protection against this disease.
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COVID-19/genética , Inmunidad Humoral/genética , Linfocitos T/metabolismo , Transcriptoma/genética , COVID-19/epidemiología , COVID-19/patología , Femenino , Humanos , Inmunidad Humoral/inmunología , Leucocitos Mononucleares/metabolismo , Masculino , MicroARNs , ARN Largo no Codificante/genética , RNA-Seq , SARS-CoV-2/genética , SARS-CoV-2/patogenicidad , Linfocitos T/inmunología , Linfocitos T/patología , Factor de Transcripción AP-1/genéticaRESUMEN
BACKGROUND: Ninety-one rodent plague epidemics have occurred in Lianghe county, Yunnan Province, China, between 1990 and 2006. This study aimed to identify predictors for the presence and abundance of small mammals in households of villages endemic for rodent plague in Lianghe county. RESULTS: Rattus flavipectus and Suncus murinus were the two species captured in 110 households. Keeping cats decreased the number of captures of R. flavipectus by one to two thirds and the chance of reported small mammal sightings in houses by 60 to 80%. Food availability was associated with fewer captures. Keeping food in sacks decreased the small mammal captures, especially of S. murinus 4- to 8-fold. Vegetables grown around house and maize grown in the village reduced the captures of S. murinus and R. flavipectus by 73 and 45%, respectively. An outside toilet and garbage piles near the house each reduced R. flavipectus captures by 39 and 37%, respectively, while raising dogs and the presence of communal latrines in the village increased R. flavipectus captures by 76 and 110% but were without detectable effect on small mammal sightings. Location adjacent to other houses increased captures 2-fold but reduced the chance of sightings to about half. In addition, raising ducks increased the chance of sighting small mammals 2.7-fold. Even after adjusting for these variables, households of the Dai had higher captures than those of the Han and other ethnic groups. CONCLUSION: Both species captures were reduced by availability of species-specific foods in the environment, whereas other predictors for capture of the two species differed. Other than the beneficial effect of cats, there were also discrepancies between the effects on small mammal captures and those on sightings. These differences should be considered during the implementation and interpretation of small mammal surveys.
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Reservorios de Enfermedades , Enfermedades Endémicas , Peste/epidemiología , Animales , Gatos , China/epidemiología , Perros , Eulipotyphla , Vivienda , Humanos , Peste/prevención & control , Peste/transmisión , Dinámica Poblacional , Ratas , Población RuralRESUMEN
@#Abstract: Objective To analyze the distribution characteristics of the main pathogens of HIV/AIDS patients with wound infections and provide basis for clinical diagnosis and treatment. Methods The clinical data of 294 patients with positive secretions or pus specimens from 2016 to 2020 were analyzed retrospectively. Results A total of 357 strains of pathogenic bacteria were isolated from 294 cases, of which 123 strains of Gram-negative bacilli (G-b), accounting for 34.5%, were mainly Escherichia coli (15.4%), Klebsiella pneumoniae (3.9%), and Pseudomonas aeruginosa (3.6%); Gram-positive bacilli (G+b) 14 strains, accounting for 3.9%; 108 Gram-positive cocci (G+c), accounting for 30.3%, of which 44 strains were coagulase-positive Staphylococcus aureus (12.3%), Coagulase-negative staphylococci were mainly Staphylococcus epidermidis (4.2%) and Staphylococcus hemolyticus (2.8%); 37 strains of fungi, accounting for 10.4%, were mainly Candida albicans (5.9%); 75 strains of Mycobacterium, accounting for 21.0%, including 41 strains of Mycobacterium tuberculosis (11.5%) and 34 strains of non-tuberculosis mycobacteria (9.5%). 52 of the 294 HIV/AIDS patients had mixed infections, accounting for 17.7%. There was significant difference in the distribution of G+c, G-b, mycobacteria and mixed infection among different specimen sources (P<0.05), and there was significant difference in the distribution of mycobacteria among different CD4+T lymphocyte counts (P<0.05). There was significant difference in the level of CD4+T lymphocytes between patients of different ages (P<0.05), and there was significant difference in the level of CD4+T lymphocytes from postoperative incision and other parts (P<0.05). Conclusions Patients with HIV/AIDS are prone to combined wound infections with various pathogenic bacteria. We should strengthen the research on wound infection in HIV/AIDS patients, and timely send patients with a low number of CD4+T lymphocytes for secretion or pus culture, so as to carry out targeted treatment and improve the prognosis of patients.
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Results from the third nationwide cluster sampling survey on the epidemiology of schistosomiasis in the People's Republic of China, conducted by the Ministry of Health in 2004, are presented. A stratified cluster random sampling technique was used, and 239 villages were selected in 7 provinces where Schistosoma japonicum remains endemic. A total of 250,987 residents 6-65 years of age were included in the survey. Estimated prevalence rates in the provinces of Hunan, Hubei, Jiangxi, Anhui, Yunnan, Sichuan, and Jiangsu were 4.2%, 3.8%, 3.1%, 2.2%, 1.7%, 0.9%, and 0.3%, respectively. The highest prevalence rates were in the lake and marshland region (3.8%) and the lowest rates were in the plain region with waterway networks (0.06%). Extrapolation to all residents in schistosome-endemic areas indicated 726,112 infections. This indicates a reduction of 16.1% compared with a nationwide survey conducted in 1995. However, human infection rates increased by 3.9% in settings where transmission is ongoing.
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Enfermedades Endémicas/estadística & datos numéricos , Esquistosomiasis Japónica/epidemiología , Adolescente , Adulto , Anciano , Animales , Niño , China/epidemiología , Análisis por Conglomerados , Enfermedades Endémicas/prevención & control , Humanos , Persona de Mediana Edad , Prevalencia , MuestreoRESUMEN
Alzheimer's disease (AD) has become the most common neurodegenerative disease. The deposition of amyloid fibrils in the brain is one of the characteristics of AD. The fibrils are composed of amyloid-ß peptide (Aß). Aß is produced through a series event of protease cleavage of a transmembrane protein called ß-amyloid precursor protein (APP) which is commonly expressed in the brain. The production of Aß and its propensity to aggregation to form oligomers and fibrils are believed to initiate a sequence of events that lead to AD dementia. The production of Aß is influenced by the transmembrane domain (TM) structure of APP. The structure variety of different Aß assemblies including oligomers and fibrils may result in different neurotoxicity to the brain. Therefore, enormous work has been carried out to study the structure of APP TM and various Aß assemblies. Solid-state NMR has advantages in studying immobile protein structures with large molecular weight. In this review, solid-state NMR structure of APP TM and different Aß assemblies will be discussed, especially various Aß amyloid fibril structures. This structural information greatly enhanced our understanding in AD, providing fundamental knowledge that will help in finding a treatment for AD.