Ferrous Sulfate-Mediated Control of Phytophthora capsici Pathogenesis and Its Impact on Pepper Plant.

Phytophthora capsici, a destructive fungal pathogen, poses a severe threat to pepper (Capsicum annuum L.) crops worldwide, causing blights that can result in substantial yield losses. Traditional control methods often come with environmental concerns or entail substantial time investments. In this research, we investigate an alternative approach involving ferrous sulfate (FeSO4) application to combat P. capsici and promote pepper growth. We found that FeSO4 effectively inhibits the growth of P. capsici in a dose-dependent manner, disrupting mycelial development and diminishing pathogenicity. Importantly, FeSO4 treatment enhances the biomass and resistance of pepper plants, mitigating P. capsici-induced damage. Microbiome analysis demonstrates that FeSO4 significantly influences soil microbial communities, particularly fungi, within the pepper root. Metabolomics data reveal extensive alterations in the redox metabolic processes of P. capsici under FeSO4 treatment, leading to compromised cell membrane permeability and oxidative stress in the pathogen. Our study presents FeSO4 as a promising and cost-effective solution for controlling P. capsici in pepper cultivation while simultaneously promoting plant growth. These findings contribute to a deeper understanding of the intricate interactions between iron, pathogen control, and plant health, offering a potential tool for sustainable pepper production.

Comparative analysis of whole genomes and transcriptomes of Microsporum canis from invasive dermatophytosis and tinea capitis.

ABSTRACTGenomes of strains of the zoophilic dermatophyte Microsporum canis from invasive (disseminated and subcutaneous) and noninvasive (tinea capitis) infections were compared. Especially the disseminated strain showed significant syntenic rearrangements, including multiple translocations and inversions, and numerous SNPs and Indels in comparison to the noninvasive strain. In transcriptome analysis, both invasive strains were enriched for GO pathways related to components of the membrane, iron binding and heme binding, which possibly enables them to invade deeper into dermis and blood vessels. At 37 °C, invasive strains showed gene expression enriched for DNA replication, mismatch repair, N-glycan biosynthesis and ribosome biogenesis. The invasive strains were slightly less susceptible to multiple antifungal agents suggesting that acquired elevated drug resistance might be involved in the refractory disease courses. Patient with disseminated infection failed to respond to a combined antifungal treatment with itraconazole, terbinafine, fluconazole and posaconazole.

Effects of omega-3 supplementation on glucose and lipid metabolism in patients with gestational diabetes: A meta-analysis of randomized controlled trials.

AIM: We assessed whether omega-3 supplementation could improve glucose and lipid metabolism, insulin resistance, and inflammatory factors in individuals with gestational diabetes mellitus (GDM). METHODS: In this meta-study, we used a random-effects or fixed-effects meta-analysis model to analyze the mean differences (MD) and corresponding 95 % confidence intervals (CI) before and after omega-3 and placebo supplementation, thus evaluating the effects of omega-3 on glucose and lipid metabolism, insulin resistance, and inflammatory factors. RESULTS: Six randomized controlled trials (331 participants) were included in the meta-analysis. The levels of fasting plasma glucose (FPG) (WMD = -0.25 mmol/L; 95 % CI: -0.38, -0.12), fasting insulin (WMD = -17.13 pmol/L; 95 % CI: -27.95, -6.30), and homeostasis model of assessment-insulin resistance (WMD = -0.51; 95 % CI: -0.89, -0.12) were lower in the omega-3 group compared to their levels in the placebo group. The results of the analysis of lipid metabolism showed that triglycerides (WMD = -0.18 mmol/L; 95 % CI: -0.29, -0.08) and very low-density lipoprotein cholesterol (WMD = -0.1 mmol/L; 95 % CI: -0.16, -0.03) decreased in the omega-3 group, while high-density lipoproteins (WMD = 0.06 mmol/L; 95 % CI: 0.02, 0.10) increased. Compared to the placebo group, inflammatory factor serum C-reactive protein (SMD = -0.68 mmol/L; 95 % CI: -0.96, -0.39) decreased in the omega-3 group. CONCLUSION: Omega-3 supplementation can decrease the levels of FPG and inflammatory factors, enhance blood lipid metabolism, and reduce insulin resistance in patients with GDM.

Triptolide-mediated downregulation of FLIPS in hepatoma cells occurs at the post-transcriptional level independently of proteasome-mediated pathways.

Cellular c-FLIP prevents apoptosis mediated by death receptor through inhibiting activation of caspase-8. Therefore, when c-FLIP is downregulated or eliminated, caspase-8 activation is promoted, and death receptor ligand-induced apoptosis is activated. It was reported that triptolide (TPL) sensitized tumor cells to TNF-α-induced apoptosis by blocking TNF-α-induced activation of NF-κB and transcription of c-IAP1 and c-IAP2. However, the effect of TPL on basal c-FLIP expression was not understood. In this study, we found that the combination of TNF-α and TPL accelerated apoptosis in human hepatocellular carcinoma cells and TNF-α-induced elevated as well as basal level of FLIPS protein were downregulated by TPL. Additionally, we demonstrated that the basal level of FLIPS in Huh7 cells was continuously downregulated following the incubation of TPL and downregulated more when dosage of TPL for treatment was increased. Subsequently, we showed that TPL reduced FLIPS level in a transcription- and degradation-independent mechanism. Our findings suggest that TPL induces loss of FLIPS at the post-transcriptional level independently of proteasome-mediated pathway, an additional mechanism of TPL sensitizing cancer cells to TNF-α-induced apoptosis.

To explore association between gamma-glutamyl transferase and type 2 diabetes using a real-world study and mendelian randomization analysis.

Aim: The association between gamma-glutamyl transferase (GGT) and type 2 diabetes mellitus (T2DM) is controversial. In this study, we investigated the association between GGT and the risk of T2DM using real-world data, Mendelian randomization (MR) analysis, and literature mining. Methods: A cross-sectional study enrolled 3,048 participants (>40 years) from a community in Northeastern China was conducted. A generalized additive model was used to examine the relation between GGT and T2DM. A two-sample MR was performed to investigate the causal effect of GGT (61,089 individuals, mostly of European ancestry) on T2DM (29,193 cases and 182,573 controls of European ancestry). Results: GGT was related to glucose metabolism indicators, such as fasting plasma glucose and glycosylated hemoglobin (P < 0.05). The odds ratios (ORs) [95% confidence interval (95% CI), P] for T2DM across the GGT categories (14-16, 17-20, 21-25, 26-35, ≥36) were 1.14 [(0.88-1.47), P = 0.330], 1.55 [(1.22-1.98), P < 0.001], 1.87 [(1.47-2.28), P < 0.001], 1.97 [(1.55-2.52), P < 0.001], and 2.29 [(1.78-2.94), P < 0.001] versus GGT ≤ 13 category after adjusting for potential confounding factors. A generalized additive model identified a non-linear correlation between GGT and T2DM and indicated that the risk of T2DM almost levelled out when GGT exceeded 34 IU/L. The MR analysis showed that the odds of having T2DM for a one-time increase in genetically determined GGT was 0.998 [(0.995-1.002), P = 0.34]. Conclusions: Our analysis of observational study suggested that GGT, its increment, within a certain range, is indicative of the development of T2DM. However, MR analysis provided no evidence that GGT is a linear causal factor of T2DM. Further investigation is required to determine if GGT exerts a non-linear causal effect on T2DM.

Inhibition of BTK improved APAP-induced liver injury via suppressing proinflammatory macrophages activation by restoring mitochondrion function.

BACKGROUND: Acetaminophen (APAP) overdose can cause severe liver injury and APAP-induced liver injury (AILI) is one of the leading causes of acute liver failure (ALF). Bruton's tyrosine kinase (BTK) is a key tyrosine kinase in immune responses, which plays an important role in many inflammatory diseases. However, its effect on AILI is still not clear. Here, we aimed to assess the effect of BTK on AILI and explore its underlying mechanism. METHODS: In our study, western blot and immunohistochemistry were used to detect the expression of BTK in AILI. The C57BL/6 mice were used to check the protective effect of BTK inhibition on AILI and the activation of BTK was confirmed in mice macrophages treated with APAP. Immunofluorescence, immunohistochemistry, oxygen consumption rate (OCR) detection, polymerase chain reaction (PCR), flow cytometry and western blot were used to determine the role of BTK in mitochondrial dynamics and function of macrophages and the underlying mechanisms in AILI. RESULTS: Our results showed that BTK upregulated in AILI. BTK inhibition protected mice from AILI and BTK was activated in mice macrophages in response to APAP. Mechanically, BTK inhibition promoted mitochondrial fusion and restored mitochondrial function through phospholipase C gamma 2 (PLCγ2)-reactive oxygen species (ROS)-Optic Atrophy 1(OPA1) pathway in macrophages and finally suppressed the release of proinflammatory cytokines. CONCLUSIONS: In conclusion, we found that BTK inhibition protected mice from AILI by restoring the mitochondrial function of macrophages through the improvement of the mitochondrial dynamic imbalance via PLCγ2-ROS-OPA1 signaling pathway, which indicated that BTK might be a potential therapeutic target of AILI.

A 20-Year Antifungal Susceptibility Surveillance (From 1999 to 2019) for Aspergillus spp. and Proposed Epidemiological Cutoff Values for Aspergillus fumigatus and Aspergillus flavus: A Study in a Tertiary Hospital in China.

The emergence of resistant Aspergillus spp. is increasing worldwide. Long-term susceptibility surveillance for clinically isolated Aspergillus spp. strains is warranted for understanding the dynamic change in susceptibility and monitoring the emergence of resistance. Additionally, neither clinical breakpoints (CBPs) nor epidemiological cutoff values (ECVs) for Aspergillus spp. in China have been established. In this study, we performed a 20-year antifungal susceptibility surveillance for 706 isolates of Aspergillus spp. in a clinical laboratory at Peking University First Hospital from 1999 to 2019; and in vitro antifungal susceptibility to triazoles, caspofungin, and amphotericin B was determined by the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method. It was observed that Aspergillus fumigatus was the most common species, followed by Aspergillus flavus and Aspergillus terreus. Forty isolates (5.7%), including A. fumigatus, A. flavus, A. terreus, Aspergillus niger, and Aspergillus nidulans, were classified as non-wild type (non-WT). Importantly, multidrug resistance was observed among A. flavus, A. terreus, and A. niger isolates. Cyp51A mutations were characterized for 19 non-WT A. fumigatus isolates, and TR34/L98H/S297T/F495I was the most prevalent mutation during the 20-year surveillance period. The overall resistance trend of A. fumigatus increased over 20 years in China. Furthermore, based on ECV establishment principles, proposed ECVs for A. fumigatus and A. flavus were established using gathered minimum inhibitory concentration (MIC)/minimum effective concentration (MEC) data. Consequently, all the proposed ECVs were identical to the CLSI ECVs, with the exception of itraconazole against A. flavus, resulting in a decrease in the non-WT rate from 6.0 to 0.6%.

Three-dimensional mapping of neurofibrillary tangle burden in the human medial temporal lobe.

Tau protein neurofibrillary tangles are closely linked to neuronal/synaptic loss and cognitive decline in Alzheimer's disease and related dementias. Our knowledge of the pattern of neurofibrillary tangle progression in the human brain, critical to the development of imaging biomarkers and interpretation of in vivo imaging studies in Alzheimer's disease, is based on conventional two-dimensional histology studies that only sample the brain sparsely. To address this limitation, ex vivo MRI and dense serial histological imaging in 18 human medial temporal lobe specimens (age 75.3 ± 11.4 years, range 45 to 93) were used to construct three-dimensional quantitative maps of neurofibrillary tangle burden in the medial temporal lobe at individual and group levels. Group-level maps were obtained in the space of an in vivo brain template, and neurofibrillary tangles were measured in specific anatomical regions defined in this template. Three-dimensional maps of neurofibrillary tangle burden revealed significant variation along the anterior-posterior axis. While early neurofibrillary tangle pathology is thought to be confined to the transentorhinal region, we found similar levels of burden in this region and other medial temporal lobe subregions, including amygdala, temporopolar cortex, and subiculum/cornu ammonis 1 hippocampal subfields. Overall, the three-dimensional maps of neurofibrillary tangle burden presented here provide more complete information about the distribution of this neurodegenerative pathology in the region of the cortex where it first emerges in Alzheimer's disease, and may help inform the field about the patterns of pathology spread, as well as support development and validation of neuroimaging biomarkers.

Molecular genotyping of Candida albicans isolated from different sites may trace the etiological infection routes: Observation in China.

BACKGROUND: Invasive candidiasis is a growing concern worldwide, especially in immunocompromised patients, including ICU patients. OBJECTIVES: As Candida albicans is the leading cause of candidaemia, it is important to investigate the evolution of C. albicans in patients with candidaemia. METHODS: We analysed 238 strains of C. albicans isolated from different body sites. Antifungal susceptibility testing, CAI loci genotyping and multilocus sequence typing (MLST) of all isolates were performed. The relationships among the total isolates that differed in sequence at only one of the seven housekeeping gene loci were analysed using eBURST. RESULTS: Multilocus sequence typing analysis in 238 isolates by combining seven housekeeping alleles revealed 175 diploid sequence types, in which 84 were newly identified. eBURST analysis for these data recognised 19 clonal complexes (CCs) and 79 singletons. Besides, seventy-three CAI genotypes were identified. Blood isolates showed maximum genotypes (49), and the dominant genotypes were CAI 17-21 and CAI 21-21. Oral isolates possessed 25 CAI genotypes, and the dominant genotypes were CAI 17-21 and CAI 21-21 as well. Since isolates with CAI allele numbers <30 showed easier transmission, CAI 17-21 and CAI 21-21 were the most frequently transmitted. Finally, the CAI genotypes were classified into six groups. CONCLUSIONS: This work revealed the oral and blood strains isolated from the patients with candidaemia in ICU shared the identical dominant CAI genotypes. Our data expanded the C. albicans MLST database and helped with understanding the evolution and spread of invasive candidiasis.

AMPK-mTOR-ULK1-mediated autophagy protects carbon tetrachloride-induced acute hepatic failure by inhibiting p21 in rats.

Autophagy is a lysosomal-dependent degradation pathway in eukaryotic cells. Recent studies have reported that autophagy can facilitate the activation of hepatic stellate cells (HSCs) and fibrogenesis of the liver during long-term carbon tetrachloride (CCl4) exposure. However, little is known about the role of autophagy in CCl4-induced acute hepatic failure (AHF). This study aimed to identify whether modulation of autophagy can affect CCl4-induced AHF and evaluate the upstream signaling pathways mediated by CCl4-induced autophagy in rats. The accumulation of specific punctate distribution of endogenous LC3-II, increased expression of LC3-II, Atg5, and Atg7 genes/proteins, and decreased expression of p62 gene were observed after acute liver injury was induced by CCl4 in rats, indicating that CCl4 resulted in a high level of autophagy. Moreover, loss of autophagic function by using chloroquine (CQ, an autophagic inhibitor) aggravated liver function, leading to increased expression of p21 (a cyclin-dependent kinase inhibitor) in CCl4-treated rats. Furthermore, the AMPK-mTORC1-ULK1 axis was found to serve a function in CCl4-induced autophagy. These results reveal that AMPK-mTORC1-ULK1 signaling-induced autophagy has a protective role in CCl4-induced hepatotoxicity by inhibiting the p21 pathway. This study suggests a useful strategy aimed at ameliorating CCl4-induced acute hepatotoxicity by autophagy.

Enhanced handover mechanism using mobility prediction in wireless networks.

The rapid increase in the usage of the mobile internet has led to a great expansion of cellular data networks in order to provide better quality of service. However, the cost to expand the cellular network is high. One of the solutions to provide affordable wireless connectivity is the deployment of a WiFi access point to offload users' data usage. Nevertheless, the frequent and inefficient handover process between the WiFi AP and cellular network, especially when the mobile device is on the go, may degrade the network performance. Mobile devices do not have the intelligence to select the optimal network to enhance the quality of service (QoS). This paper presents an enhanced handover mechanism using mobility prediction (eHMP) to assist mobile devices in the handover process so that users can experience seamless connectivity. eHMP is tested in two wireless architectures, homogeneous and heterogeneous networks. The network performance significantly improved when eHMP is used in a homogeneous network, where the network throughput increases by 106% and the rate of retransmission decreases by 85%. When eHMP is used in a heterogeneous network, the network throughput increases by 55% and the retransmission rate decreases by 75%. The findings presented in this paper reveal that mobility prediction coupled with the multipath protocol can improve the QoS for mobile devices. These results will contribute to a better understanding of how the network service provider can offload traffic to the WiFi network without experiencing performance degradation.

Characterization of hippocampal subfields using ex vivo MRI and histology data: Lessons for in vivo segmentation.

Hippocampal subfield segmentation on in vivo MRI is of great interest for cognition, aging, and disease research. Extant subfield segmentation protocols have been based on neuroanatomical references, but these references often give limited information on anatomical variability. Moreover, there is generally a mismatch between the orientation of the histological sections and the often anisotropic coronal sections on in vivo MRI. To address these issues, we provide a detailed description of hippocampal anatomy using a postmortem dataset containing nine specimens of subjects with and without dementia, which underwent a 9.4 T MRI and histological processing. Postmortem MRI matched the typical orientation of in vivo images and segmentations were generated in MRI space, based on the registered annotated histological sections. We focus on the following topics: the order of appearance of subfields, the location of subfields relative to macroanatomical features, the location of subfields in the uncus and tail and the composition of the dark band, a hypointense layer visible in T2-weighted MRI. Our main findings are that: (a) there is a consistent order of appearance of subfields in the hippocampal head, (b) the composition of subfields is not consistent in the anterior uncus, but more consistent in the posterior uncus, (c) the dark band consists only of the CA-stratum lacunosum moleculare, not the strata moleculare of the dentate gyrus, (d) the subiculum/CA1 border is located at the middle of the width of the hippocampus in the body in coronal plane, but moves in a medial direction from anterior to posterior, and (e) the variable location and composition of subfields in the hippocampal tail can be brought back to a body-like appearance when reslicing the MRI scan following the curvature of the tail. Our findings and this publicly available dataset will hopefully improve anatomical accuracy of future hippocampal subfield segmentation protocols.

Global Screening of Genomic and Transcriptomic Factors Associated with Phenotype Differences between Multidrug-Resistant and -Susceptible Candida haemulonii Strains.

Candida haemulonii, a close relative of Candida auris, is an emerging pathogen which frequently shows multidrug resistance especially to triazoles, the most used antifungal drugs. The mechanisms of drug resistance in C. haemulonii, however, are largely unknown. Here, we sequenced and annotated the genomes of two reference strains from the C. haemulonii complex, compared the phenotypes, genomes, and transcriptomes of a triazole-susceptible and two triazole-resistant C. haemulonii strains, and identified triazole susceptibility, morphology, fitness, and the major genetic and gene expression differences between the strains. A multidrug efflux gene, CDR1, was recurrently found to be upregulated for expression in triazole-resistant strains. Blocking the activity of Cdr1 increased the susceptibility to triazoles strikingly. Comparative transcriptome analysis also demonstrated impaired cell wall integrity, filamentous growth, and iron homeostasis in triazole-resistant strains. Finally, we also identified a zinc-binding MHR family transcription regulator gene that mutated in triazole-resistant strains spontaneously, contributing to the changes of morphology and, possibly, cell wall integrity between the strains. The study provided important clues for future studies exploring the mechanisms of multidrug resistance and related phenotypic differences of C. haemulonii strains.IMPORTANCE A comprehensive, multi-omic survey was performed to disclose the genetic backgrounds and differences between multidrug-resistant and -susceptible C. haemulonii strains. Genes were identified with mutations or significant expression differences in multidrug-resistant compared to multidrug-susceptible strains, which were mainly involved in multidrug resistance, stress fitness, and morphology. The Cdr1-encoding gene, C. haemulonii 2486 (CH_2486), was expressed at a significantly increased level in multidrug-resistant strains. Functional inhibition experiments further implicated potential roles of CH_2486 in drug resistance. A gene spontaneously mutated in resistant strains, CH_4347, was experimentally validated to influence the morphology of spores, possibly by controlling cell wall integrity.

Screening the in vitro susceptibility of posaconazole in clinical isolates of Candida spp. and Aspergillus spp. and analyzing the sequence of ERG11 or CYP51A in non-wild-type isolates from China.

The present study was to determine the in vitro activity of posaconazole (POS) against 385 Candida and 268 Aspergillus clinical isolates from China. We found that POS was active against 85.5% Candida and 94.4% Aspergillus isolates. Non-wild-type (non-WT) phenotype was found in a subset of Candida albicans (15.4%), Candida tropicalis (11.9%), Aspergillus fumigatus (4.1%), and Aspergillus flavus (17.4%) isolates. Cross-resistance to POS and other triazoles was seen. Gene sequencing showed that 4 C. albicans, 1 C. tropicalis, and 9 A. fumigatus isolates with cross-resistance to POS and other triazoles had mutations in ERG11 or CYP51A. In conclusion, POS has potent in vitro activity against most of Candida and Aspergillus isolates from China. Non-WT phenotype and those with cross-resistance to POS and other triazoles exist, frequently driven by mutations of ERG11 in Candida spp. and CYP51A in Aspergillus spp.

Evaluation of the novel nanoparticle material - CdSe quantum dots on Chlorella pyrenoidosa and Scenedesmus obliquus: Concentration-time-dependent responses.

Quantum dots (QDs), as a kind of novel nanomaterial, have the extensive applications in various fields, inevitably leading to increasing risks for the ecological environment. The mobilization of cadmium including metal smelting and subsequent machining for multifarious applications has caused the release of cadmium element into the environment. In this study, we evaluated the potential toxicity of a novel nanoparticle material CdSe QDs, using two green algae Chlorella pyrenoidosa and Scenedesmus obliquus. The impact of CdSe QDs and cadmium ions on algae and the sensitivity of the two algae on target compounds were also considered and compared. Our results showed the algal growth rates and chlorophyll content decreased with increasing exposure concentrations and durations. Moreover, the glutathione levels were decreased while the activities of superoxide dismutase increased, exhibiting their pivotal functions in defeating toxic stress. The increment of malondialdehyde levels revealed that the stresses of CdSe QDs and cadmium ions were contributed to the occurrence of oxidative damage. Our study also indicated that the impact of CdSe QDs was stronger than that of cadmium nitrate and the algal response was also species-specific. In addition, the TEM photographs of the algal ultrastructure showed the presence of surface attachment and uptake of QDs.

Genome-Wide Analysis, Expression Profile, and Characterization of the Acid Invertase Gene Family in Pepper.

Catalytic decomposition of sucrose by acid invertases (AINVs) under acidic conditions plays an important role in the development of sink organs in plants. To reveal the function of AINVs in the development of pepper fruits, nine AINV genes of pepper were identified. Protein sequencing and phylogenetic analysis revealed that the CaAINV family may be divided into cell wall invertases (CaCWINV1⁻7) and vacuolar invertases (CaVINV1⁻2). CaAINVs contain conserved regions and protein structures typical of the AINVs in other plants. Gene expression profiling indicated that CaCWINV2 and CaVINV1 were highly expressed in reproductive organs but differed in expression pattern. CaCWINV2 was mainly expressed in buds and flowers, while CaVINV1 was expressed in developmental stages, such as the post-breaker stage. Furthermore, invertase activity of CaCWINV2 and CaVINV1 was identified via functional complementation in an invertase-deficient yeast. Optimum pH for CaCWINV2 and CaVINV1 was found to be 4.0 and 4.5, respectively. Gene expression and enzymatic activity of CaCWINV2 and CaVINV1 indicate that these AINV enzymes may be pivotal for sucrose hydrolysis in the reproductive organs of pepper.

HBV Facilitated Hepatocellular Carcinoma Cells Proliferation by Up-Regulating Angiogenin Expression Through IL-6.

BACKGROUND/AIMS: Patients with hepatitis B virus (HBV) infection are at a high risk of developing hepatocellular carcinoma (HCC). In this study, we aim to investigate the roles of HBV on angiogenin (ANG), as well as the effects on cell proliferation in presence of ANG down-regulation. METHODS: Serum ANG was determined by ELISA. The expression of ANG mRNA and protein in HCC cell lines with or without HBV/HBx were determined. Western blot and ELISA were conducted to determine the effects of HBV/HBx on IL-6 expression. The role of IL-6 on ANG was evaluated by IL-6 recombinant protein or IL-6 neutralizing antibody. Immunofluorescence staining was used to detect the nuclear translocation of ANG. MTT was performed to evaluate the relative inhibition ratio. RESULT: In vivo experiments showed elevation of serum ANG in patients infected with HBV. In vitro experiments showed HBV and HBx contributed to the transcription and translation of ANG. ANG expression showed increase after IL-6 stimulation, and ANG protein decreased in the presence of IL-6 blocking with its antibody. HBV promoted nuclear translocation of ANG. Inhibiting ANG expression or blocking of nuclear transfer of ANG attenuated the 45S rRNA synthesis and cell proliferation. CONCLUSION: HBV and HBx protein can increase the level of ANG through IL-6. HBV and HBx contributed to the nuclear translocation of ANG. Cell proliferation was inhibited after inhibiting the expression or nuclear transfer of ANG.

The Influence of B and T Lymphocyte Attenuator Genetic Variants on Susceptibility to Chronic Hepatitis B Virus Infection.

BACKGROUND/AIMS: B and T lymphocyte attenuator (BTLA) is an immune inhibitory receptor involved in the pathogenesis of chronic viral infections. Little is known about the effects of BTLA gene polymorphisms on chronic hepatitis B virus (HBV) infections. In this study, we investigated whether the polymorphisms of BTLA are associated with the progression of chronic HBV infection. METHODS: A total of 382 chronic HBV carriers and 170 healthy individuals in the same region were recruited for this study. The chronic HBV carriers were divided into three groups: asymptomatic HBV carriers (ASC), moderate chronic hepatitis B group (MCHB), and severe chronic hepatitis B group (SCHB). Two BTLA functional single nucleotide polymorphisms (SNPs; rs76844316 and rs9288952) were genotyped by polymerase chain reaction and sequenced directly. RESULTS: The results showed that the frequency of the G allele of rs76844316 was significantly lower in the SCHB group than in the other three groups. Subjects bearing at least one G allele (TG or GG genotype) at rs76844316 had decreased susceptibility to severe chronic hepatitis B compared with those bearing the TT genotype. Haplotype analysis of the two SNPs revealed that the frequency of the G-G haplotype was significantly lower in SCHB patients than in controls. Moreover, in the SCHB group, patients carrying the G allele of rs76844316 tended to have lower ALT levels than those without it. CONCLUSION: Our findings suggest that the genetic variants of rs76844316 in BTLA influence the susceptibility to severe chronic hepatitis B and might play a protective role against the progression of chronic hepatitis B.

Characterizing the human hippocampus in aging and Alzheimer's disease using a computational atlas derived from ex vivo MRI and histology.

Although the hippocampus is one of the most studied structures in the human brain, limited quantitative data exist on its 3D organization, anatomical variability, and effects of disease on its subregions. Histological studies provide restricted reference information due to their 2D nature. In this paper, high-resolution (∼200 × 200 × 200 µm3) ex vivo MRI scans of 31 human hippocampal specimens are combined using a groupwise diffeomorphic registration approach into a 3D probabilistic atlas that captures average anatomy and anatomic variability of hippocampal subfields. Serial histological imaging in 9 of the 31 specimens was used to label hippocampal subfields in the atlas based on cytoarchitecture. Specimens were obtained from autopsies in patients with a clinical diagnosis of Alzheimer's disease (AD; 9 subjects, 13 hemispheres), of other dementia (nine subjects, nine hemispheres), and in subjects without dementia (seven subjects, nine hemispheres), and morphometric analysis was performed in atlas space to measure effects of age and AD on hippocampal subfields. Disproportional involvement of the cornu ammonis (CA) 1 subfield and stratum radiatum lacunosum moleculare was found in AD, with lesser involvement of the dentate gyrus and CA2/3 subfields. An association with age was found for the dentate gyrus and, to a lesser extent, for CA1. Three-dimensional patterns of variability and disease and aging effects discovered via the ex vivo hippocampus atlas provide information highly relevant to the active field of in vivo hippocampal subfield imaging.

Genome-Wide Identification, Expression, and Functional Analysis of the Alkaline/Neutral Invertase Gene Family in Pepper.

Alkaline/neutral invertase (NINV) proteins irreversibly cleave sucrose into fructose and glucose, and play important roles in carbohydrate metabolism and plant development. To investigate the role of NINVs in the development of pepper fruits, seven NINV genes (CaNINV1-7) were identified. Phylogenetic analysis revealed that the CaNINV family could be divided into α and ß groups. CaNINV1-6 had typical conserved regions and similar protein structures to the NINVs of other plants, while CaNINV7 lacked amino acid sequences at the C-terminus and N-terminus ends. An expression analysis of the CaNINV genes in different tissues demonstrated that CaNINV5 is the dominant NINV in all the examined tissues (root, stem, leaf, bud, flower, and developmental pepper fruits stage). Notably, the expression of CaNINV5 was found to gradually increase at the pre-breaker stages, followed by a decrease at the breaker stages, while it maintained a low level at the post-breaker stages. Furthermore, the invertase activity of CaNINV5 was identified by functional complementation of the invertase-deficient yeast strain SEY2102, and the optimum pH of CaNINV5 was found to be ~7.5. The gene expression and enzymatic activity of CaNINV5 suggest that it might be the main NINV enzyme for hydrolysis of sucrose during pepper fruit development.