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Background and Aims: Data on the safety and effectiveness of tenofovir alafenamide (TAF) plus peginterferon-alpha (Peg-IFN-α) in children with chronic hepatitis B (CHB) are lacking. The current study aimed to present the characteristics of four pediatric CHB patients who obtained a functional cure by using TAF and Peg-IFN-α. Methods: In this case series study initiated in May 2019, ten children who had no clinical symptoms or signs received response-guided (HBV DNA undetectable, hepatitis B e antigen [HBeAg] loss or seroconversion, and hepatitis B surface antigen [HBsAg] loss or seroconversion) and functional cure-targeted (HBsAg loss or seroconversion) TAF (25 mg/d, orally) plus Peg-IFN-α-2b (180 µg/1.73m2, subcutaneously, once weekly) in combination (9/10) or sequential (1/10) therapy. The safety and effectiveness of these treatments were monitored. Results: As of April 2024, four out of ten children obtained a functional cure after a mean of 31.5 months of treatment, and the other six children are still undergoing treatment. These four cured children, aged 2, 4, 8, and 6 years, were all HBeAg-positive and had alanine aminotransferase levels of 80, 47, 114, and 40 U/L; HBV DNA levels of 71200000, 93000000, 8220, and 96700000 IU/mL; and HBsAg levels of 39442.8, 15431.2, 22, and 33013.1 IU/mL, respectively. During treatment, all the children (10/10) experienced mild or moderate adverse events, including flu-like symptoms, anorexia, fatigue, and cytopenia. Notably, growth retardation (8/10) was the most significant adverse event; and it occurred in three cured children (3/4) treated with combination therapy and was present to a low degree in the other cured child (1/4) treated with sequential therapy. Fortunately, all three cured children recovered to or exceeded the normal growth levels at 9 months posttreatment. Conclusions: TAF plus Peg-IFN-α-2b therapy is potentially safe and effective for pediatric CHB patients, which may provide important insights for future clinical practice and study designs targeting functional cures for children with CHB. [ABSTRACT FROM AUTHOR]

In this work, carbon nitride (C3N4) powder was oxidized by the Hummers oxidation method, and oxidized carbon nitride (O‐C3N4) was obtained. Epoxy (EP) was modified with O‐C3N4, and then carbon fiber fabric/epoxy (CF/EP) composites were prepared by hand‐pasting molding. The O‐C3N4 greatly improves the wettability of EP resin, enhances the interface properties of CF/EP composites, and makes the composites have better mechanical properties. The interlaminar shear strength (ILSS) is increased from 51.75 to 59.68 MPa, the tensile strength is increased from 564.54 to 635.39 MPa, the bending strength is increased from 809.64 to 938.81 MPa, and the impact strength is increased from 73.48 to 84.84 kJ/m2. Meanwhile, the dynamic mechanical properties of composites are also significantly improved. The energy storage modulus is increased from 14.9 to 21.4 GPa, with an increase of 43.6%. Highlights: Developing carbon fiber composites is conducive to industrial applications.O‐C3N4 effectively improves the mechanical properties of the composite.O‐C3N4 has the advantages of simple synthesis, low costs, and light color.O‐C3N4 is rich in oxygen‐containing functional groups. [ABSTRACT FROM AUTHOR]

Background Few safety and effectiveness results have been published regarding the administration of tenofovir alafenamide fumarate (TAF) during pregnancy for the prevention of mother-to-child transmission (MTCT) of hepatitis B virus (HBV). Methods In this multicenter prospective observational study, pregnant women with HBV DNA levels higher than 200 000 IU/mL who received TAF or tenofovir disoproxil fumarate (TDF) from gestational weeks 24–35 to delivery were 1:1 enrolled and followed until postpartum month 6. Infants received immunoprophylaxis. The primary endpoint was the safety of mothers and infants. The secondary endpoint was the hepatitis B surface antigen (HBsAg)-positive rate at 7 months for infants. Results In total, 116 and 116 mothers were enrolled, and 117 and 116 infants were born, in the TAF and TDF groups, respectively. TAF was well tolerated during a mean treatment duration of 11.0 weeks. The most common maternal adverse event was nausea (19.0%). One (0.9%), 3 (2.6%), and 9 (7.8%) mothers had abnormal alanine aminotransferase levels at delivery and at postpartum months 3 and 6, respectively. The TDF group had safety profiles that were comparable to those of the TAF group. No infants had birth defects in either group. The infants' physical and neurological development at birth and at 7 months in the TAF group were comparable with those in the TDF group. The HBsAg positive rate was 0% at 7 months in all 233 infants. Conclusions Antiviral prophylaxis with TAF was determined to be generally safe for both mothers and infants and reduced the MTCT rate to 0%. [ABSTRACT FROM AUTHOR]

Background None of the current guidelines recommend antiviral therapy for inactive hepatitis B virus (HBV) carriers (IHCs). Methods In this real-world, multicenter, nonrandomized study, 32 participants meeting the inclusion criteria were enrolled 1:1 for treatment with peginterferon α-2b or monitoring without treatment based on participant preference. The expected treatment duration was 48 weeks. The primary end point was hepatitis B surface antigen (HBsAg) loss. The HBV vaccine could be injected after HBsAg loss. Results All patients had HBsAg levels of <20 IU/mL. The mean baseline HBsAg levels were 6.6 IU/mL and 5.8 IU/mL in the treated and untreated groups, respectively. Fifteen (93.8%) participants achieved HBsAg loss, 5 obtained HBsAg seroconversion after undergoing a mean of 19.7 weeks of therapy in the treated group, and no one in the follow-up group achieved HBsAg loss during a mean follow-up time of 12.6 months (P <.0001). Generally, the therapy was well tolerated. Nine of 11 individuals who exhibited HBsAg loss benefited from receiving the HBV vaccine. Conclusions This study provides justification for further studies of short-course peginterferon α-2b for the functional cure of IHCs with low HBsAg levels. Additionally, HBV vaccine injection is beneficial after interferon-induced HBsAg loss. [ABSTRACT FROM AUTHOR]

Interleukin (IL)‐17A is pro‐inflammatory cytokine which has been identified as a noninvasive marker of the pathogenesis of non‐alcoholic steatohepatitis (NASH). However, the underlying role of IL‐17A in NASH progression remains unclear. This study was designed to investigate the biological function and molecular mechanism of IL‐17A in the induction of NASH. The results showed that IL‐17A was highly expressed in high‐fat diet (HFD)‐induced NASH mouse model. Intravenous injection of IL‐17A exacerbated steatohepatitis process via promoting hepatocyte apoptosis. Furthermore, IL‐17A‐induced apoptosis was mediated by ERK1/2/p65 signaling pathway. In conclusion, we demonstrated that IL‐17A‐mediated ERK1/2/p65 signaling pathway was a promising target for the treatment of NASH. © 2018 IUBMB Life, 71(3):302–309, 2019 [ABSTRACT FROM AUTHOR]

Background: The medicinal plant, Catharanthus roseus (C. roseus), accumulates a wide range of terpenoid indole alkaloids (TIAs). Ethylene (ET) and methyl-jasmonate (MeJA) were previously reported as effective elicitors for the production of various valuable secondary metabolites of C. roseus, while a few ET or MeJA induced transcriptomic research is yet reported on this species. In this study, the de-novo transcriptome assembly of C. roseus is performed by using the next-generation sequencing technology. Results: The result shows that phenolic biosynthesis genes respond specifically to ET in leaves, monoterpenoid biosynthesis genes respond specifically to MeJA in roots. By screening the database, 23 ATP-binding cassette (ABC) transporter partial sequences are identified in C. roseus. On this basis, more than 80 key genes that encode key enzymes (namely TIA pathway, transcriptional factor (TF) and candidate ABC transporter) of alkaloid synthesis in TIA biosynthetic pathways are chosen to explore the integrative responses to ET and MeJA at the transcriptional level. Our data indicated that TIA accumulation is strictly regulated by the TF ethylene responsive factor (ERF) and bHLH iridoid synthesis 1 (BIS1). The heatmap, combined with principal component analysis (PCA) of C. roseus, shows that ERF co-expression with ABC2 and ABC8 specific expression in roots affect the root-specific accumulation of vinblastine in C. roseus. On the contrast, BIS1 activities follow a similar pattern of ABC3 and CrTPT2 specific expression in leaves, which affects the leaf-specific accumulation of vindoline in C. roseus. Conclusions: Results presented above illustrate that ethylene has a stronger effect than MeJA on TIA induction at both transcriptional and metabolite level. Furthermore, meta-analysis reveals that ERF and BIS1 form a positive feedback loop connecting two ABC transporters respectively and are actively involved in TIAs responding to ET and MeJA in C. roseus. [ABSTRACT FROM AUTHOR]

Japanese dodder ( Cuscuta japonica) is a flowering, parasitic weed that causes major yield losses on crop and forest production. In the present field study, the influence of Cuscuta on the growth and secondary metabolite of its host medicinal shrub Madagascar periwinkle ( Catharanthus roseus) was investigated. Vegetative and reproductive growth of the host plant Catharanthus was measured at intervals from 0 to 60 days after inoculation (DAI), and content of three alkaloids, naturally produced by the host, in the host and parasite were measured by HPLC at intervals from 15 to 45 DAI. Dodder infection significantly inhibited biomass accumulation and reproductive growth of Catharanthus, and aerial parts of the host died by 60 DAI. Levels of alkaloids vinblastine, vindoline and catharanthine in the inoculated Catharanthus were lower than in uninoculated control plants, both in immature leaf and in mature leaf, except the alkaloids contents were elevated in host immature leaf compared with uninoculated control plants immature leaf at 15 days. The host plant thus actively responded to dodder infection by accumulating alkaloids acts as a defense molecule at 15 DAI. The alkaloids produced by host plants accumulated in dodder at 15-45 DAI, and the alkaloid content in dodder reached a maximum at 45 DAI. The alkaloids transported from host to parasite act as a sink, the high content of alkaloids in dodder be cytotoxic and accelerated the onset of senescence. [ABSTRACT FROM AUTHOR]

We selected different concentrations of ethephon, to stress C. roseus. We used qRT-PCR and HPLC followed by PCA to obtain comprehensive profiling of the vinblastine biosynthesis in response to ethephon. Based on our findings, the results showed that the high concentration of ethephon had a positive effect at both transcriptional and metabolite level. Meanwhile, there was a remarkable decrease of hydrogen peroxide content and a promoted peroxidase activity in leaves. The loading plot combination with correlation analysis suggested that CrPrx1 could be regarded as a positive regulator and interacts with ethylene response factor (ERF) to play a key role in vinblastine content and peroxidase (POD) activity. This study provides the foundation for a better understanding of the regulation and accumulation of vinblastine in response to ethephon. [ABSTRACT FROM AUTHOR]

Many plants in the family Apocynaceae have been used for medicinal purposes.Catharanthus roseusandVinca minorare the most important medicinal plants that belong to the Apocynaceae family. A procedure is reported for the determination of the bioactive alkaloids tabersonine, serpentine, vindoline, catharanthine, tryptamine, and vincamine in Apocynaceae plants (C. roseusandV. minor) by liquid chromatography electrospray ionization tandem mass spectrometry. Quantitation was performed from positive multiple reactions at 161.4 → 144.2, 349.4 → 263.0, 457.6 → 188.0, 337.5 → 168.3, 337.4 → 144.2, 355.4 → 337.2, and 854.5 → 286.4 for tryptamine, serpentine, vindoline, tabersonine, catharanthine, vincamine, and paclitaxel (the internal standard), respectively. The optimized method was employed for the determination of the active alkaloids in the leaves ofC. roseusandV. minorby liquid chromatography–tandem mass spectrometry. [ABSTRACT FROM PUBLISHER]

Research on transcriptional regulation of terpenoid indole alkaloid (TIA) biosynthesis of the medicinal plant, Catharanthus roseus, has largely been focused on gene function and not clustering analysis of multiple genes at the transcript level. Here, more than ten key genes encoding key enzyme of alkaloid synthesis in TIA biosynthetic pathways were chosen to investigate the integrative responses to exogenous elicitor ethylene and copper (Cu) at both transcriptional and metabolic levels. The ethylene-induced gene transcripts in leaves and roots, respectively, were subjected to principal component analysis (PCA) and the results showed the overall expression of TIA pathway genes indicated as the Q value followed a standard normal distribution after ethylene treatments. Peak gene expression was at 15-30 μM of ethephon, and the pre-mature leaf had a higher Q value than the immature or mature leaf and root. Treatment with elicitor Cu found that Cu up-regulated overall TIA gene expression more in roots than in leaves. The combined effects of Cu and ethephon on TIA gene expression were stronger than their separate effects. It has been documented that TIA gene expression is tightly regulated by the transcriptional factor (TF) ethylene responsive factor (ERF) and mitogen-activated protein kinase (MAPK) cascade. The loading plot combination with correlation analysis for the genes of C. roseus showed that expression of the MPK gene correlated with strictosidine synthase ( STR) and strictosidine b- d-glucosidase( SGD). In addition, ERF expression correlated with expression of secologanin synthase ( SLS) and tryptophan decarboxylase ( TDC), specifically in roots, whereas MPK and myelocytomatosis oncogene ( MYC) correlated with STR and SGD genes. In conclusion, the ERF regulates the upstream pathway genes in response to heavy metal Cu mainly in C. roseus roots, while the MPK mainly participates in regulating the STR gene in response to ethylene in pre-mature leaf. Interestingly, the change in TIA accumulation does not correlate with expression of the associated genes. Our previous research found significant accumulation of vinblastine in response to high concentration of ethylene and Cu suggesting the involvement of posttranscriptional and posttranslational mechanisms in a spatial and temporal manner. In this study, meta-analysis reveals ERF and MPK form a positive feedback loop connecting two pathways actively involved in response of TIA pathway genes to ethylene and copper in C. roseus. [ABSTRACT FROM AUTHOR]