RESUMEN
Although a combination of immunoprophylaxis and antiviral therapy can effectively prevent mother-to-child transmission (MTCT) of hepatitis B virus (HBV), a considerable number of infants born to highly viremic mothers still develop occult HBV infection (OBI). To uncover the virological factor and risk predictor for OBI in infants, we found that the diversity and complexity of maternal HBV quasispecies in the case group were lower than those in the control group. Mutations with significant differences between the two groups were most enriched in the NTCPbd and PreC regions. Genetic distance at the amino-acid level of the PreC region, especially the combination of three amino-acid mutations in the PreC region, could strongly predict the risk of OBI in infants. HBV quasispecies in OBI infants were highly complex, and the non-synonymous substitutions were mainly found in the RT and HBsAg regions. The sK47E (rtQ55R) and sP49L mutations in OBI infants might contribute to OBI through inhibiting the production of HBV DNA and HBsAg, respectively. This study found the potential virological factors and risk predictors for OBI in infants born to highly viremic mothers, which might be helpful for controlling OBI in infants.
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ADN Viral , Virus de la Hepatitis B , Hepatitis B , Transmisión Vertical de Enfermedad Infecciosa , Mutación , Cuasiespecies , Viremia , Humanos , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/clasificación , Virus de la Hepatitis B/aislamiento & purificación , Femenino , Cuasiespecies/genética , Hepatitis B/virología , Hepatitis B/transmisión , ADN Viral/genética , Lactante , Embarazo , Adulto , Antígenos de Superficie de la Hepatitis B/genética , Antígenos de Superficie de la Hepatitis B/sangre , Recién Nacido , Complicaciones Infecciosas del Embarazo/virología , Masculino , Madres , GenotipoRESUMEN
BACKGROUND: The long-term protective effect of hepatitis B vaccine (HepB), the incidence of hepatitis B virus (HBV) vaccine breakthrough infections (VBIs), and whether a booster HepB is necessary remain to be clarified in children born to mothers with chronic HBV infection. METHODS: Based on a long-term follow-up prospective cohort of 1177 hepatitis B surface antigen (HBsAg)-positive mothers and their paired infants which was established from 2009 to 2011, total 454 children with immunoprophylaxis success as determined by postvaccination serologic testing (PVST) at 7 months old were included in this study. Among the 454 children, 246 never had a booster HepB, and 208 children received a booster HepB from 1 to 5 years of age. Multivariate logistic regression analysis was used to analyse the risk factors for HBV VBIs. RESULTS: The hepatitis B surface antibody (anti-HBs) levels declined sharply from 7 months to 2 years old, and the anti-HBs seronegative rate in the children increased significantly from 2 years old. A total of 31 (6.83%) of the 454 children experienced VBIs, of which 7 had overt and 7 had occult HBV infections. Notably, 14 (45.16%) of the 31 children with VBIs were diagnosed at 2 years old, and all of them had anti-HBs positivity (> 10 mIU/mL) at 1 year old. Maternal hepatitis B e antigen (HBeAg) positivity, higher HBV DNA and HBsAg levels, lower initial infant anti-HBs levels and not receiving a booster HepB were independent risk factors for VBIs. The incidence of VBIs was significantly lower in children with a booster HepB than in nonboosted children (0.50 vs. 11.90%, P < 0.001), and none of the boosted children developed overt or occult HBV infection. The anti-HBs levels of 76.67% for the children with VBIs in the nonboosted group indicated positivity before VBIs was detected. CONCLUSIONS: After the primary full immunization with HepB, children born to mothers with chronic HBV infection, especially the children with maternal HBeAg positivity, high HBV DNA levels, high HBsAg levels and/or low initial infant anti-HBs levels, were at a high risk of VBIs, and a booster HepB for these children before 2 years old, instead of when their anti-HBs level is < 10 mIU/mL, could reduce the incidence of VBIs.
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Vacunas contra Hepatitis B , Hepatitis B Crónica , Humanos , Niño , Lactante , Preescolar , Antígenos de Superficie de la Hepatitis B , Antígenos e de la Hepatitis B , ADN Viral , Estudios Prospectivos , Anticuerpos contra la Hepatitis B , Hepatitis B Crónica/epidemiología , Hepatitis B Crónica/prevención & control , Hepatitis B Crónica/tratamiento farmacológico , Complicaciones Posoperatorias/tratamiento farmacológicoRESUMEN
Although characterization of the baseline oral microbiota has been discussed, the current literature seems insufficient to draw a definitive conclusion on the interactions between the microbes themselves or with the host. This study focuses on the spatial and temporal characteristics of the oral microbial ecosystem in a mouse model and its crosstalk with host immune cells in homeostasis. The V3V4 regions of the 16S rRNA gene of 20 samples from four niches (tongue, buccal mucosa, keratinized gingiva and hard palate) and 10 samples from two life stages (adult and old) were analysed. Flow cytometry (FCM) was used to investigate the resident immune cells. The niche-specialist and age-related communities, characterized based on the microbiota structure, interspecies communications, microbial functions and interactions with immune cells, were addressed. The phylum Firmicutes was the major component in the oral community. The microbial community profiles at the genus level showed that the relative abundances of the genera Bacteroides, Lactobacillus and Porphyromonas were enriched in the gingiva. The abundance of the genera Streptococcus, Faecalibaculum and Veillonella was increased in palatal samples, while the abundance of Neisseria and Bradyrhizobium was enriched in buccal samples. The genera Corynebacterium, Stenotrophomonas, Streptococcus and Fusobacterium were proportionally enriched in old samples, while Prevotella and Lacobacillus were enriched in adult samples. Network analysis showed that the genus Lactobacillus performed as a central node in the buccal module, while in the gingiva module, the central nodes were Nesterenkonia and Hydrogenophilus. FCM showed that the proportion of Th1 cells in the tongue samples (38.18â% [27.03-49.34â%]) (mean [range]) was the highest. The proportion of γδT cells in the buccal mucosa (25.82â% [22.1-29.54â%]) and gingiva (20.42â% [18.31-22.53â%]) samples was higher (P<0.01) than those in the palate (14.18â% [11.69-16.67â%]) and tongue (9.38â% [5.38-13.37â%] samples. The proportion of Th2 (31.3â% [16.16-46.44â%]), Th17 (27.06â% [15.76-38.36â%]) and Treg (29.74â% [15.71-43.77â%]) cells in the old samples was higher than that in the adult samples (P<0.01). Further analysis of the interplays between the microbiomes and immune cells indicated that Th1 cells in the adult group, nd Th2, Th17 and Treg cells in the old group were the main immune factors strongly associated with the oral microbiota. For example, Th2, Th17 and Treg cells showed a significantly positive correlation with age-related microorganisms such as Sphingomonas, Streptococcus and Acinetobacter, while Th1 cells showed a negative correlation. Another positive correlation occurred between Th1 cells and several commensal microbiomes such as Lactobacillus, Jeotgalicoccus and Sporosarcina. Th2, Th17 and Treg cells showed the opposite trend. Together, our findings identify the niche-specialist and age-related characteristics of the oral microbial ecosystem and the potential associations between the microbiomes and the mucosal immune cells, providing critical insights into mucosal microbiology.
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Microbiota , Animales , Firmicutes/genética , Homeostasis , Lactobacillus/genética , Ratones , Microbiota/genética , ARN Ribosómico 16S/genética , Streptococcus/genéticaRESUMEN
Background: The existence of hepatic cancer stem cells (CSCs) contributes to chemotherapy resistance and cancer recurrence after treatment or surgery. However, very little is known about the hepatitis B virus (HBV) replication and its relationship with the stemness of hepatocellular carcinoma (HCC) in HBV-related HCC patients. Methods: We collected tumor tissues (T), matched adjacent non-tumor tissues (NT), and distal non-tumor tissues (FNT) from 55 HCC patients for analysis. Results: We found HBV DNA levels were higher in T samples than NT and FNT samples, but HBV pgRNA and total RNA expressed lower in T samples. HBV pgRNA and total RNA correlate to HBV DNA among the T, NT, and FNT samples. Further evidence for HBV replication in T samples was provided by HBV S, reverse transcriptase, and X genes sequencing, showing that HBV sequences and genotypes differed between T and matched NT and FNT samples. HBV pgRNA and total RNA showed more frequent significant correlations with CSC markers in NT samples in HBsAg-positive patients. The markers CD133 and OCT4 expressed higher in FNT samples, and HBV replication marker of pgRNA levels was significantly positively correlated to these two markers only in FNT samples. The detection of pgRNA and OCT4 in FNT was correlated to the recurrence of HCC in the resection of HCC patients. Analysis of HBV receptor, sodium taurocholate co-transporting polypeptide (NTCP), showed that NTCP was correlated negatively to CSC markers in T samples, except for the CD44. Conclusion: HBV replication may present in HCC with a weak transcriptomic signature. Moreover, the expression level of HBV pgRNA in distal non-tumor tissues is a sensitive marker for HBV replication and prognosis, which is associated with CSC-related markers especially with OCT4 in distal non-tumor tissues and recurrence of HCC in HBV-related HCC patients.
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BACKGROUND: Previous works have observed that younger infants with chronic hepatitis B virus (HBV) infection are more responsive to antiviral treatment. However, the underlying mechanism remains unclear. In this study, the dynamic changes of HBV quasispecies in infants with immunoprophylaxis failure were investigated to provide virological explanations for clinical management on infantile antiviral therapy. METHODS: Thirteen 7-month-old infants with immunoprophylaxis failure and their mothers were enrolled from a prospective cohort, and 8 of them were followed up to 3 years old. The sequences of HBV quasispecies were analyzed by the full-length genome clone-based sequencing, and compared among mothers and their infants at different ages. RESULTS: The results revealed that the complexity, mutation frequency and genetic distance of HBV quasispecies decreased significantly at full-length, partial open reading frames and regulatory regions of HBV genome at nucleotide level in 7-month-old infants comparing with their mothers, whereas increased significantly to near the maternal level when infants grew up to 3 years old. Furthermore, similar changes were also found in Core, PreS2, RT and P regions of HBV genome at amino acid level, especially for potential NAs-resistant mutants in RT region and immune-escape mutants in Core and PreS2 regions. CONCLUSIONS: This study uncovered the evolution of HBV quasispecies in infancy after mother-to-child transmission, which may provide the virological evidence for explaning that younger children are more responsive to antiviral therapy.
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Hepatitis B Crónica , Hepatitis B , Niño , Estudios de Cohortes , ADN Viral , Femenino , Hepatitis B/prevención & control , Virus de la Hepatitis B/genética , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Lactante , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Estudios Prospectivos , CuasiespeciesRESUMEN
OBJECTIVES: To describe a new sonographic feature of the C-sign for prenatal diagnosis of jejunal atresia and evaluate its role in prenatal jejunal atresia, particularly preceding bowel dilatation and polyhydramnios. METHODS: This was a retrospective study from a tertiary maternal hospital. Patients with prenatal sonographic examination and confirmed small bowel atresia postdelivery were included. All sonographic images were reviewed by two senior sonographers. Comparison of sonographic images between prenatal jejunal and ileal atresia using the C-sign resembles the shape of the entire duodenum and other traditional sonographic features. The control group without bowel atresia was assessed for the presence of the C-sign. RESULTS: The C-sign and combined bowel dilatation with polyhydramnios were more frequent in jejunal atresia than ileal atresia, but the C-sign can be used to detect jejunal atresia earlier. The C-sign can be more likely to diagnose jejunal atresia in persisting bowel dilatation and polyhydramnios. The C-sign was not reported in any of the control fetuses. CONCLUSION: The C-sign is a new sonographic feature that can be used to improve the prenatal accuracy and early detection of jejunal atresia. However, further prospective validation is needed.
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Atresia Intestinal , Femenino , Humanos , Atresia Intestinal/diagnóstico por imagen , Yeyuno/diagnóstico por imagen , Embarazo , Estudios Retrospectivos , Ultrasonografía , Ultrasonografía PrenatalRESUMEN
Corn starch (CS), potato starch (PtS), and pea starch (PS) were modified by ultrasonic frequency (codes as UFCS, UFPtS and UFPS), and changes in aggregation structure, digestibility and rheology were investigated. For UFCS, the apparent amylose content and gelatinization enthalpy (∆H) decreased, while the R1047/1022 values and relative crystallinity (RC) increased under lower ultrasonic frequencies (20 kHz and 25 kHz). For UFPtS, the apparent amylose content, R1047/1022 values and RC increased, while the ∆H decreased under a higher ultrasonic frequency (28 kHz). For UFPS, the apparent amylose content, R1047/1022 values, RC, ∆H decreased at 20 kHz, 25 kHz and 28 kHz. Cracks were observed on the surface of UFCS, UFPtS and UFPS. These aggregation structure changes increased the resistant starch content to 31.11% (20 kHz) and 26.45% (25 kHz) for UFCS and to 39.68% (28 kHz) for UFPtS, but decreased the resistant starch content to 18.46% (28 kHz) for UFPS. Consistency coefficient, storage modulus, and loss modulus of UFCS, UFPtS and UFPS increased, while the flow behavior index and damping factor decreased. Results indicated that CS, PtS and PS had diverse digestion and rheology behaviors after ultrasonic frequency modification, which fulfilled different demands in starch-based products.
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Digestión , Pisum sativum/química , Reología , Solanum tuberosum/química , Almidón/química , Ultrasonido , Zea mays/química , Amilosa/análisis , Módulo de Elasticidad , Hidrólisis , Cinética , Tamaño de la Partícula , Espectroscopía Infrarroja por Transformada de Fourier , Almidón/ultraestructura , TemperaturaRESUMEN
Ultrasound was widely used in starch modification, whereas there was no review focusing on the effects of different ultrasonic treatments on A-, B- and C-type starches. In this study, the effects of ultrasonic power (UP, 100-600 W) and ultrasonic time (UT, 5-35 min) on structural, digestibility and rheology of corn starch (CS), potato starch (PtS), and pea starch (PS) were investigated. As a result, UP and UT decreased the apparent amylose content of CS and PS, while increased the apparent amylose content of PtS. UP and UT enhanced R1047/1022 values of CS, whereas those of PtS and PS were decreased. Moreover, UP and UT decreased the gelatinization enthalpy of CS, PtS and PS. In vitro digestion revealed that UP and UT decreased the resistant starch content of PtS and PS, but increased the resistant starch content of CS. Rheological tests indicated that UP and UT decreased the flow behavior index of CS, PtS and PS pastes, and caused an increase in storage modulus and loss modulus. Results revealed that ultrasonic treatment represented a promising technology to obtain CS, PtS and PS with tailored digestibility and rheology, which allowed the texture and glycemic response of starch-based products to be adjusted.
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Pisum sativum/química , Solanum tuberosum/química , Almidón/química , Zea mays/química , Rastreo Diferencial de Calorimetría , Reología , Espectroscopía Infrarroja por Transformada de Fourier , Ondas UltrasónicasRESUMEN
The effect of sonication temperature on the structures and digestion behaviour of corn starch (CS, A-type), potato starch (PtS, B-type), and pea starch (PS, C-type) was investigated. For CS, sonication temperature resulted in a rough surface, decreased apparent amylose content, gelatinization enthalpy and gelatinization degree, increased short-range orders, long-range orders, retrogradation degree and resistant starch content. For PtS, sonication temperature led to a coarser surface with scratches, increased apparent amylose content and gelatinization degree, decreased short-range orders, long-range orders, gelatinization enthalpy, retrogradation degree, and resistant starch content. For PS, sonication temperature showed partial disintegration on surface, increased gelatinization degree, decreased apparent amylose content, short-range orders, long-range orders, gelatinization enthalpy, retrogradation degree and resistant starch content. This study suggested that starch digestion features could be controlled by the crystalline pattern of starch used and the extent of sonication temperature, and thus were of value for rational control of starch digestion features.
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Pisum sativum/química , Solanum tuberosum/química , Almidón/química , Almidón/farmacocinética , Zea mays/química , Amilosa/análisis , Amilosa/química , Digestión , Gelatina/química , Sonicación , TemperaturaRESUMEN
As a high-risk factor of perinatal HBV transmission, the potential role of maternal hepatitis B e antigen (HBeAg) to guide antiviral prophylaxis has not yet been fully reported. This large prospective cohort study enrolled 1177 hepatitis B surface antigen (HBsAg)-positive pregnant women without antiviral treatment and their newborns. HBeAg, HBsAg, and viral load in maternal serum collected before delivery were measured. All the newborns were given standard passive-active immunoprophylaxis within 12â h after birth, and post-vaccination serologic testing was performed at 7 (±7d) months of age. The results revealed that 20 of the 1177 infants (1.70%) were immunoprophylaxis failure, and all their mothers were HBeAg positive. Maternal quantitative HBeAg was positively correlated with viral load (r = 0.83; P < .0001) and quantitative HBsAg (r = 0.68; P < .0001). The area under the receiver operating characteristic curve (AUC) for predicting immunoprophylaxis failure by maternal HBeAg was comparable to that by maternal viral load (0.871 vs 0.893; P = .441) and HBsAg (0.871 vs 0.871; P = .965). The optimal cutoff value of maternal quantitative HBeAg to predict perinatal infection was 2.21 log10 PEI U/mL, and the sensitivity and specificity was 100.0% and 74.5%, respectively. According to maternal viral load >2 × 105 IU/mL, the sensitivity and specificity of maternal qualitative HBeAg to identify the risk of HBV MTCT for pregnant women and determine the necessity for antiviral prophylaxis was 95.5% and 92.6%, respectively. This study showed that maternal HBeAg can be a surrogate marker of HBV DNA for monitoring and evaluating whether antiviral prophylaxis is necessary for preventing perinatal HBV transmission.
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Antígenos de Superficie de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis B/prevención & control , Hepatitis B/virología , Complicaciones Infecciosas del Embarazo/virología , Adolescente , Adulto , Antivirales/uso terapéutico , Área Bajo la Curva , China/epidemiología , ADN Viral , Femenino , Hepatitis B/epidemiología , Hepatitis B/transmisión , Virus de la Hepatitis B/genética , Humanos , Inmunización Pasiva , Inmunoterapia Activa , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Filogenia , Embarazo , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Pruebas Serológicas , Carga Viral , Adulto JovenRESUMEN
Objectives: In view of the concern expressed about the current references, new references for fetal biparietal diameter and head circumference should be constructed for contemporary local populations.Methods: We conducted a retrospective cross-sectional study in two hospitals in Guangdong, Southern China. Fetal biparietal diameter and head circumference percentiles regression were fitted using Cole's LMS method. The BPD and HC data were then transformed into Z-scores that were calculated using two series of reference equations obtained from two methods: Cole's LMS method and the original "mean and SD method." Each Z-score distribution was presented as the mean and standard deviation. Finally, the sensitivity and specificity of each reference for identifying fetuses <2.5th or >97.5th percentile (based on the observed distribution of Z-scores) were calculated. The misclassified number and Youden's index were listed.Results: A total of 17,974 biparietal diameter and 18,269 head circumference measurements were chosen to establish a reference chart. The LMS method could fit the local population better than the "mean and SD method" as it had a lower number of misclassified fetuses and a higher Youden's index.Conclusion: The Cole's LMS method was able to construct a satisfied reference range of fetal head sizes in Southern China.
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Feto , Ultrasonografía Prenatal , China , Estudios Transversales , Femenino , Edad Gestacional , Humanos , Embarazo , Valores de Referencia , Estudios RetrospectivosRESUMEN
Chemically modified starch (RS4) was commercially available as a food ingredient, however, there was a lack of knowledge on how ultrasonic treatment (non-thermal technology) modulated the enzymatic resistance of RS4. In this study, structural change of RS4 during ultrasonic treatment and its resulting digestibility was investigated. Results from scanning electron microscopy, particle size analysis, chemical composition analysis, X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopy showed that ultrasonic treatment remained the granule morphology, increased the apparent amylose content, reduced the particle size, destroyed the crystalline structure, decreased the helical orders, but enhanced the short-range molecular orders of ultrasonic-processed RS4. In vitro digestibility analysis showed that the total content of rapidly digestible starch and slowly digestible starch was increased, whereas the content of resistant starch was decreased. Overall, ultrasonic treatment substantially reduced the enzymatic resistance of RS4, indicating that RS4 was not stability against the non-thermal processing technology of ultrasonic treatment.
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Digestión , Sonicación/métodos , Almidón/metabolismo , Rastreo Diferencial de Calorimetría , Conformación de Carbohidratos , Técnicas In Vitro , Espectroscopía Infrarroja por Transformada de Fourier , Almidón/química , Difracción de Rayos XRESUMEN
Occult hepatitis B virus (HBV) infection (OBI) has been observed among infants born to hepatitis B surface antigen (HBsAg)-positive mothers despite successful immunoprophylaxis. This study enrolled 549 infants [349 infants received a 10µg/dose of hepatitis B vaccine (HepB), and 200 infants received 20µg/dose HepB] born to HBsAg-positive mothers with HBV DNA load >6log10IU/mL. The anti-HBs levels in the 10µg group were significantly lower than that in the 20µg group both at 7 [652.48 (564.05-754.82) vs. 1541.72 (1268.69-1873.51) mIU/mL, P<0.001] and 12 months old [257.44 (220.29-300.88) vs. 1073.41 (839.27-1372.78) mIU/mL, P<0.001]. The OBI incidence in the 10µg group was significantly higher than that in the 20µg group at both 7 [21.55% (25/116) vs. 7.56% (9/119), P=0.002] and 12 months old [17.07% (14/82) vs. 6.90% (6/87), P=0.041]. OBI incidence in infants with anti-HBs levels <100mIU/mL was higher than that of those with anti-HBs ≥100mIU/mL [35.71% (5/14) vs. 13.12% (29/221), P=0.036]. This study showed that increasing the immunisation dose from 10µg to 20µg significantly improved anti-HBs levels and decreased OBI incidence in infants with a high maternal viral load. We recommend 20µg HepB to treat this high-risk population.
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Infecciones Asintomáticas/epidemiología , Anticuerpos contra la Hepatitis B/sangre , Vacunas contra Hepatitis B/inmunología , Virus de la Hepatitis B/inmunología , Hepatitis B/prevención & control , Antígenos de Superficie de la Hepatitis B/análisis , Vacunas contra Hepatitis B/administración & dosificación , Antígenos e de la Hepatitis B/análisis , Humanos , Lactante , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa/estadística & datos numéricos , Estudios Prospectivos , Vacunación , Carga ViralRESUMEN
OBJECTIVE: This study was performed to explore the correlation between the characteristics of hepatitis B virus (HBV) quasispecies in HBV-infected pregnant women and the risk of immunoprophylaxis failure for their infants. DESIGN: In this prospective nested case-control study, the characteristics of HBV quasispecies in mothers whose infants were immunoprophylaxis success (control group) and those whose infants were immunoprophylaxis failure (case group) were analysed by the clone-based sequencing of full-length HBV genome and next-generation sequencing (NGS) of "a" determinant region, and were compared between the two groups. RESULTS: The quasispecies characteristics including mutant frequency, Shannon entropy and mean genetic distance at amino acid level of "a" determinant region were significantly lower in case group than that in control group, using the full-length HBV genome clone-based sequencing assay. These results were confirmed by NGS assay. Notably, we discovered that the differences were also significant at nucleotide level by NGS assay. Furthermore, the risk of immunoprophylaxis failure could be predicted by analysing the three HBV quasispecies characteristics either at nucleotide level or at amino acid level of "a" determinant region, and the corresponding predictive values were tentatively set up. CONCLUSIONS: HBV quasispecies with a more complex mutant spectrum in "a" determinant region might be more vulnerable to extinct through mother-to-child-transmission (MTCT). More importantly, analysing HBV quasispecies characteristics in pregnant women with high HBV DNA load might be helpful to predict the high-risk population of immunoprophylaxis failure, and consequently provide accurate intervention against MTCT of HBV.
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Antígenos e de la Hepatitis B/inmunología , Virus de la Hepatitis B/patogenicidad , Hepatitis B/transmisión , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Complicaciones Infecciosas del Embarazo/prevención & control , Adulto , Estudios de Casos y Controles , ADN Viral/inmunología , Femenino , Virus de la Hepatitis B/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Inmunización/métodos , Embarazo , Complicaciones Infecciosas del Embarazo/genética , Prevención Primaria/métodos , Estudios Prospectivos , Cuasiespecies/genética , Valores de Referencia , Sensibilidad y Especificidad , Carga Viral/genéticaRESUMEN
Viruses could rapidly diversify into variants, which has long been known to facilitate viral adaption in the host. Recent studies showed that cooperation among variants and wild-type (WT) also increased viral fitness. Here, a mutant of sC69∗ in small hepatitis B surface protein (SHBs) that resulted in premature stop was investigated and the frequency of sC69∗ was 4.37% (19/435), most of which coexisted with the WT (78.95%, 15/19), indicating mixed viral populations. Functional studies showed that sC69∗ mutant was associated with lower viral spread, but could be rescued by coexisting with the WT. The sC69∗ mutant showed to attenuate host innate immune response during infection and poly (I:C) treatment such as IL29, ISG15, and RIG-I (p < 0.05). The lower immune response was not caused by the lower replication of sC69∗ mutant. Our data provide information that sC69∗ coexisting with the WT might facilitate the fitness and persistence of the viral quasispecies in the host.
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The maintenance of terminally differentiated cells, especially hepatocytes, in vitro has proven challenging. Here we demonstrated the long-term in vitro maintenance of primary human hepatocytes (PHHs) by modulating cell signaling pathways with a combination of five chemicals (5C). 5C-cultured PHHs showed global gene expression profiles and hepatocyte-specific functions resembling those of freshly isolated counterparts. Furthermore, these cells efficiently recapitulated the entire course of hepatitis B virus (HBV) infection over 4 weeks with the production of infectious viral particles and formation of HBV covalently closed circular DNA. Our study demonstrates that, with a chemical approach, functional maintenance of PHHs supports long-term HBV infection in vitro, providing an efficient platform for investigating HBV cell biology and antiviral drug screening.
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Virus de la Hepatitis B/crecimiento & desarrollo , Hepatocitos/fisiología , Hepatocitos/virología , Cultivo Primario de Células/métodos , Cultivo de Virus/métodos , Antivirales/aislamiento & purificación , Antivirales/farmacología , ADN Circular/biosíntesis , ADN Circular/aislamiento & purificación , ADN Viral/biosíntesis , ADN Viral/aislamiento & purificación , Evaluación Preclínica de Medicamentos , Virus de la Hepatitis B/efectos de los fármacos , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Humanos , Transcriptoma , Virión/efectos de los fármacos , Virión/crecimiento & desarrolloRESUMEN
Cassava is the third largest food crop of the world and has strong ability of drought tolerance. In order to evaluate the molecular diversity and to discover novel alleles for drought tolerance in cassava germplasms, we examined a total of 107 abiotic stress related expressed sequence tags-simple sequence repeat (EST-SSR) markers in 134 cassava genotypes coming from planting regions worldwide and performed drought related marker-traits association mapping. As results, we successfully amplified 98 of 107 markers in 97 polymorphic loci and 279 alleles, with 2.87 alleles per locus, gene diversity of 0.48 and polymorphic information content (PIC) of 0.41 on average. The genetic coefficient between every two lines was 0.37 on average, ranging from 0.21 to 0.82. According to our population structure analysis, these samples could be divided into three sub-populations showing obvious gene flow between them. We also performed water stress experiments using 100-day old cassava plants in two years and calculated the drought tolerance coefficients (DTCs) and used them as phenotypes for marker-trait association mapping. We found that 53 markers were significantly associated with these drought-related traits, with a contribution rate for trait variation of 8.60% on average, ranging between 2.66 and 28.09%. Twenty-four of these 53 associated genes showed differential transcription or protein levels which were confirmed by qRT-PCR under drought stress when compared to the control conditions in cassava. Twelve of twenty-four genes were the same differential expression patterns in omics data and results of qRT-PCR. Out of 33 marker-traits combinations on 24 loci, 34 were positive and 53 negative alleles according to their phenotypic effects and we also obtained the typical materials which carried these elite alleles. We also found 23 positive average allele effects while 10 loci were negative according to their allele effects (AAEs). Our results on molecular diversity, locus association and differential expression under drought can prove beneficial to select excellent materials through marker assisted selection and for functional genes research in the future.
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Sequías , Etiquetas de Secuencia Expresada , Repeticiones de Microsatélite/genética , Alelos , Biomarcadores , Mapeo Cromosómico , Variación Genética/genética , Genotipo , Manihot/química , Fenotipo , Polimorfismo de Nucleótido Simple/genética , Sitios de Carácter Cuantitativo/genéticaRESUMEN
The 2-fold interpenetrated 3D framework 1 can be solvent-induced to noninterpenetrated framework 1' in a reversible single crystal-single crystal transformation fashion. In addition, 1' represents the first catalyst based on triazole to catalyze the aerobic homocoupling of various substituted arylboronic acids.