A New Nonlinear Photothermal Iterative Theory for Port-Wine Stain Detection.

The development of appropriate photothermal detection of skin diseases to meet complex clinical demands is an urgent challenge for the prevention and therapy of skin cancer. An extensive body of literature has ignored all high-order harmonics above the second order and their influences on low-order harmonics. In this paper, a new iterative numerical method is developed for solving the nonlinear thermal diffusion equation to improve nonlinear photothermal detection for the noninvasive assessment of the thickness of port-wine stain (PWS). First, based on the anatomical and structural properties of skin tissue of PWS, a nonlinear theoretical model for photothermal detection is established. Second, a corresponding nonlinear thermal diffusion equation is solved by using the new iterative numerical method and taking into account harmonics above the second-order and their effects on lower-order harmonics. Finally, the thickness and excitation light intensity of PWS samples are numerically simulated. The simulation results show that the numerical solution converges fasterand the physical meaning of the solution is clearerwith the new method than with the traditional perturbation method. The rate of change in each harmonic with the sample thickness for the new method is higher than that for the conventional perturbation method, suggesting that the proposed numerical method may provide greater detection sensitivity. The results of the study provide a theoretical basis for the clinical treatment of PWS.

Effects of microplastics on soil microbiome: The impacts of polymer type, shape, and concentration.

Increasing research has recognized that the ubiquitous presence of microplastics in terrestrial environments is undeniable, which potentially alters the soil ecosystem properties and processes. The fact that microplastics with diverse characteristics enter into the soil may induce distinct effects on soil ecosystems. Our knowledge of the impacts of microplastics with different polymers, shapes, and concentrations on soil bacterial communities is still limited. To address this, we examined the effects of spherical microplastics (150 µm) with different polymers (i.e., polyethylene (PE), polystyrene (PS), and polypropylene (PP)) and four shapes of PP microplastics (i.e., fiber, film, foam, and particle) at a constant concentration (1%, w/w) on the soil bacterial community in an agricultural soil over 60 days. Treatments with different concentrations (0.01-20%, w/w) of PP microplastic particles (150 µm) were also included. The bacterial communities in PE and PP treatments showed a similar pattern but separated from those in PS-treated soils, indicating the polymer backbone structure is an important factor modulating the soil bacterial responses. Fiber, foam, and film microplastics significantly affected the soil bacterial composition as compared to the particle. The community dissimilarity of soil bacteria was significantly (R2 = 0.592, p < 0.001) correlated with the changes of microplastic concentration. The random forest model identified that certain bacteria belonging to Patescibacteria were closely linked to microplastic contamination. Additionally, analysis of the predicted function further showed that microplastics with different characteristics caused distinct effects on microbial community function. Our findings suggested that the idiosyncrasies of microplastics should not be neglected when studying their effects on terrestrial ecosystems.

Enhanced serum interferon-lambda 1/interleukin-29 levels in patients with psoriasis vulgaris

Abstract Background: Interferon (IFN)-λ1, also named Interleukin (IL)-29, is a new member of the Type III IFN or IFN-λ family. IL-29 plays an important role in the pathogenesis of many types of autoimmune and inflammatory diseases. Objective: To study the role of IL-29 in the pathogenesis of psoriasis vulgaris. Methods: The authors detected the serum levels of IL-29 in forty-one patients with psoriasis vulgaris, twenty-three patients with atopic dermatitis and thirty-eight age and gender-matched controls by sandwich Enzyme-Linked Immunosorbent Assay (ELISA). The effects of IL-29 on the expression of cytokines, such as IL-6, IL-17, IL-8, IL-4, IL10, Interferon (IFN-γ) and Tumor Necrosis Factor-α (TNF-α), in PBMCs and HaCat cells were determined by real-time quantitative PCR. Results: Our data indicated that serum IL-29 levels were significantly elevated in patients with psoriasis vulgaris when compared with atopic dermatitis patients and the control group. Moreover, Serum levels of IL-29 were closely associated with the severity of psoriasis vulgaris. Furthermore, IL-29 up-regulated the mRNA expression levels of IL-6, IL-17 and TNF-α in PBMCs from psoriasis vulgaris patients. In addition, IL-29 enhanced the IL-6 and IL-8 expression from the HaCat cells. Conclusion: This study provides the first observations on the association of IL-29 and psoriasis vulgaris and showed elevated IL-29 serum levels. The authors suggest that IL-29 may play a role in the pathogenesis of psoriasis vulgaris.

A Highly Selective Supramolecule Array Membrane Made of Zero-Dimensional Molecules for Gas Separation.

We orderly assembled zero-dimensional 2-methylimidazole (mim) molecules into unprecedented supramolecule array membranes (SAMs) through solvent-free vapor processing, realizing the intermolecular spacing of mim at ca. 0.30 nm available as size-sieving channels for distinguishing the tiny difference between H2 (kinetic diameter: 0.289 nm) and CO2 (kinetic diameter: 0.33 nm). The highly oriented and dense membranes yield a separation factor above 3600 for equimolar H2 /CO2 mixtures, which is one order of magnitude higher than those of the state-of-the-art membranes defining 2017's upper bound for H2 /CO2 separation. These SAMs define a new benchmark for molecular sieve membranes and are of paramount importance to precombustion carbon capture. Given the range of supramolecules, we anticipate SAMs with variable intermolecular channels could be applied in diversified separations that are prevalent in chemical processes.

Morin Acts as a USP7 Inhibitor to Hold Back the Migration of Rheumatoid Arthritis Fibroblast-Like Synoviocytes in a "Prickle1-mTORC2" Dependent Manner.

INTRODUCTION: The aim of this study is to investigate the effect and detailed mechanisms of morin, an anti-arthritis compound widely distributed in foods of plant origin, on the pathological migration of fibroblast-like synoviocytes (FLS). METHODS AND RESULTS: The migration of FLS collected from arthritis rats and MH7A cells is induced by platelet-derived growth factor, and an arthritis model in rats is established by Freund's complete adjuvant. The results show that morin remarkably restrains FLS migration but slightly affects FLS apoptosis and proliferation. Moreover, in the progression of FLS migration, focal adhesion (FA) turnover is inhibited by morin via lowering the activation of Paxillin and focal adhesion kinase (FAK) and internalization of integrin ß1. Morin disrupts the formation of mTOR complex 2 (mTORC2) and the activation of AKT (S473) and PKCα (S657), and MHY1485 reverses morin-limited FLS migration. Of note, the protein stability of Prickle1, a binding factor of Rictor, is reduced by morin, and MG132 but not Baf A1 shows a repressive effect. Finally, the target protein is identified as ubiquitin-specific protease 7 (USP7) but not USP9X. USP7 overexpressing plasmid weakens morin-affected protein and ubiquitination of Prickle1, and mechanisms are confirmed in vivo by using an overexpressing plasmid and inhibitor. CONCLUSION: Morin restricts FLS migration and arthritis by intervening in "USP7-Prickle1-mTORC2" signaling and FA turnover.

Enhanced serum interferon-lambda 1 interleukin-29 levels in patients with psoriasis vulgaris.

BACKGROUND: Interferon (IFN)-λ1, also named Interleukin (IL)-29, is a new member of the Type III IFN or IFN-λ family. IL-29 plays an important role in the pathogenesis of many types of autoimmune and inflammatory diseases. OBJECTIVE: To study the role of IL-29 in the pathogenesis of psoriasis vulgaris. METHODS: The authors detected the serum levels of IL-29 in forty-one patients with psoriasis vulgaris, twenty-three patients with atopic dermatitis and thirty-eight age and gender-matched controls by sandwich Enzyme-Linked Immunosorbent Assay (ELISA). The effects of IL-29 on the expression of cytokines, such as IL-6, IL-17, IL-8, IL-4, IL10, Interferon (IFN-γ) and Tumor Necrosis Factor-α (TNF-α), in PBMCs and HaCat cells were determined by real-time quantitative PCR. RESULTS: Our data indicated that serum IL-29 levels were significantly elevated in patients with psoriasis vulgaris when compared with atopic dermatitis patients and the control group. Moreover, Serum levels of IL-29 were closely associated with the severity of psoriasis vulgaris. Furthermore, IL-29 up-regulated the mRNA expression levels of IL-6, IL-17 and TNF-α in PBMCs from psoriasis vulgaris patients. In addition, IL-29 enhanced the IL-6 and IL-8 expression from the HaCat cells. CONCLUSION: This study provides the first observations on the association of IL-29 and psoriasis vulgaris and showed elevated IL-29 serum levels. The authors suggest that IL-29 may play a role in the pathogenesis of psoriasis vulgaris.

The role of GLS1-mediated glutaminolysis/2-HG/H3K4me3 and GSH/ROS signals in Th17 responses counteracted by PPARγ agonists.

Background: Peroxisome proliferator-activated receptor gamma (PPARγ) has the ability to counter Th17 responses, but the full mechanisms remain elusive. Herein, we aimed to elucidate this process in view of cellular metabolism, especially glutaminolysis. Methods: MTT, CCK-8, Annexin V-FITC/PI staining or trypan blue exclusion assays were used to analyze cytotoxicity. Flow cytometry and Q-PCR assays were applied to determine Th17 responses. The detection of metabolite levels using commercial kits and rate-limiting enzyme expression using western blotting assays was performed to illustrate the metabolic activity. ChIP assays were used to examine H3K4me3 modifications. Mouse models of dextran sulfate sodium (DSS)-induced colitis and house dust mite (HDM)/lipopolysaccharide (LPS)-induced asthma were established to confirm the mechanisms studied in vitro. Results: The PPARγ agonists rosiglitazone and pioglitazone blocked glutaminolysis but not glycolysis under Th17-skewing conditions, as indicated by the detection of intracellular lactate and α-KG and the fluorescence ratios of BCECF-AM. The PPARγ agonists prevented the utilization of glutamine and thus directly limited Th17 responses even when Foxp3 was deficient. The mechanisms were ascribed to restricted conversion of glutamine to glutamate by reducing the expression of the rate-limiting enzyme GLS1, which was confirmed by GLS1 overexpression. Replenishment of α-KG and 2-HG but not succinate weakened the effects of PPARγ agonists, and α-KG-promoted Th17 responses were dampened by siIDH1/2. Inhibition of KDM5 but not KDM4/6 restrained the inhibitory effect of PPARγ agonists on IL-17A expression, and the H3K4me3 level in the promoter and CNS2 region of the il-17 gene locus down-regulated by PPARγ agonists was rescued by 2-HG and GLS1 overexpression. However, the limitation of PPARγ agonists on the mRNA expression of RORγt was unable to be stopped by 2-HG but was attributed to GSH/ROS signals subsequent to GLS1. The exact role of PPARγ was proved by GW9662 or PPARγ knockout, and the mechanisms for PPARγ-inhibited Th17 responses were further confirmed by GLS1 overexpression in vivo. Conclusion: PPARγ agonists repressed Th17 responses by counteracting GLS1-mediated glutaminolysis/2-HG/H3K4me3 and GSH/ROS signals, which is beneficial for Th17 cell-related immune dysregulation.

Downregulation of long non-coding RNA LOC101928477 correlates with tumor progression by regulating the epithelial-mesenchymal transition in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the deadliest malignancies. There is a growing body of evidence showing that long non-coding RNAs (lncRNAs) play critical roles in ESCC oncogenesis. The present study aimed to explore the role of LOC101928477, a newly discovered lncRNA, in the development and metastasis of ESCC. METHODS: In this study, real-time PCR, western blotting, cell counting kit-8 (CCK-8), flow cytometry, colony formation, wound healing, transwell migration/invasion assay, immunofluorescence, and immunohistochemistry were used. We also applied an in situ xenograft mouse model and a lung metastasis mouse model to verify our findings. RESULTS: We determined that LOC101928477 expression was inhibited in ESCC tissue and ESCC cell lines when compared with controls. Moreover, forced expression of LOC101928477 effectively inhibited ESCC cell proliferation, colony formation, migration, and invasion via suppression of epithelial-mesenchymal transition (EMT). Furthermore, LOC101928477 overexpression inhibited in situ tumor growth and lung metastasis in a mouse model. CONCLUSIONS: Together, our results suggested that LOC101928477 could be a novel suppressor gene involved in ESCC progression.

NFE2L2/KEAP1 Mutations Correlate with Higher Tumor Mutational Burden Value/PD-L1 Expression and Potentiate Improved Clinical Outcome with Immunotherapy.

BACKGROUND: Abnormalities in the KEPA1-NRF2 pathway have a role in cancer progression, metastasis, and resistance to chemo- and radiotherapies. Persistent activation of NRF2 associates with poor prognosis across different cancer types. However, the beneficial therapeutic strategy to harness this pathway in cancer remains unclear. This study aimed to investigate the clinical outcome with immunotherapy in NFE2L2/KEAP1 mutant population. MATERIALS AND METHODS: We investigated the correlation between NFE2L2/KEAP1 mutations and tumor mutational burden (TMB) and programmed death-ligand 1 (PD-L1) expression status to identify the therapeutic vulnerability. For this purpose, relevance analysis with TMB value was performed in 9,040 patients with cancer, and relevance analysis with PD-L1 expression was performed in 3,457 patients. The Memorial Sloan Kettering Cancer Center (MSKCC) database and real-world evidence were used to assess the immunotherapy response in NFE2L2/KEAP1 mutant subsets. RESULTS: NFE2L2/KEAP1 mutations occurred in various cancers, and the highest mutation incidences occurred in lung squamous cell carcinoma (LUSC) at 19.16% (NFE2L2) and 10.31% (KEAP1). We confirmed that higher TMB value and PD-L1 expression were associated with NFE2L2/KEAP1 mutations compared with wild-type, especially in non-small lung cancer. MSKCC database analysis showed the improved survival of patients with NFE2L2/KEAP1 mutant with immunotherapy compared with other treatments (median overall survival 22.52 VS 12.89, p = .0034). Real-world evidence further confirmed the efficacy of immunotherapy in the mutant population. CONCLUSION: Our study revealed that patients with NFE2L2/KEAP1 mutant could achieve improved outcomes from immunotherapy than the other treatments. These findings may broaden the application of immune checkpoint blockade to patients harboring NFE2L2/KEAP1 mutations. IMPLICATIONS FOR PRACTICE: NFE2L2/KEAP1 alterations occur frequently in multiple cancer types and are associated with poor prognosis; however, the efficacious strategy to inhibit this pathway in cancer is poorly understood. This study was designed to analyze the mutational characteristics of NFE2L2/KEAP1 alterations in 9,243 Chinese patients. The highest mutation incidences occurred in lung squamous cell carcinoma at 19.16% (NFE2L2) and 10.31% (KEAP1). Relevance analysis showed the NFE2L2/KEAP1 mutant subsets were associated with higher tumor mutational burden value and programmed death-ligand 1 expression. Clinical data further confirmed NFE2L2/KEAP1 mutations correlate with improved outcome with immunotherapy. These findings suggest the clinical application of immunotherapy in the NFE2L2/KEAP1 mutant population.

Effect of anti-inflammatory compounds or antibiotic administration on receiving performance and physiological responses of transported heifers.

The objectives of this experiment was to evaluate the effects of products with anti-inflammatory properties (yeast product [YEA; 20 g/heifer daily] or astragalus polysaccharide [APS; 20 g/heifer daily]) or an antibiotic (TUL, tulathromycin; 0.025 mL/kg body weight [BW]) on receiving performance and stress responses of transported heifers. Angus heifers (n = 80) were ranked by BW (315 ± 6 kg) and assigned to one of four treatments (five pens per treatment, four heifers per pen) 7 d before shipping 1,400 km (day -7): 1) fed a basal diet of ad libitum hay and concentrate supplement (CON) from day -7 to day 29; 2) YEA in supplemental concentrate from day -7 to day 7 (YEA); 3) APS in supplemental concentrate from day -7 to day 7 (APS); 4) administration of TUL at loading for shipping (day 0; TUL). Upon arrival at the receiving facility (day 1), heifers within each treatment were ranked by BW and assigned to 20 feedlot pens in the same manner as pre-transport. Daily dry matter intake (DMI) was recorded from day 1 to day 28. Full BW was recorded on days -7, -1, 0, 1, 28, and 29. Blood samples were collected on days -7, -1, 1, 4, 7, 14, and 28. Over the receiving period, average daily gain (ADG) and gain: feed did not differ (P ≥ 0.19) for YEA, APS, and TUL, which were greater (P ≤ 0.01) than CON. Average daily gain was also lower (P < 0.01) for CON vs. YEA, APS, and TUL from day -7 to day 28. During the first week of receiving, hay, concentrate, and total DMI were lower (P < 0.01) in CON than the YEA, APS, and TUL, but did not differ (P ≥ 0.13) among these three groups. Hay and total DMI were still lower (P < 0.01) in CON vs. TUL in the second week. Total DMI was greater (P = 0.01) for TUL vs. YEA, and greater (P < 0.01) for YEA vs. CON. Serum nonesterified fatty acid concentrations were greater (P ≤ 0.05) for CON and TUL vs. YEA and APS on day 1. Plasma cortisol concentrations were greater (P ≤ 0.05) for YEA and CON vs. APS and TUL on day 1. Serum tumor necrosis factor-α concentrations were lower (P ≤ 0.05) for APS vs. CON, YEA, and TUL on days 1 and 4. Plasma haptoglobin concentrations were greater (P ≤ 0.05) for CON vs. YEA, APS, and TUL on days 1 and 4, greater (P ≤ 0.05) for YEA, APS vs. TUL on day 1, and greater (P = 0.03) for YEA vs. TUL on day 4. Plasma ceruloplasmin concentrations were greater (P ≤ 0.05) for CON vs. YEA, APS and TUL vs. APS on days 1, 4, and 7. In conclusion, YEA, APS, and TUL modulated the physiological stress responses and alleviated the performance losses caused by long-distance transportation.

Household Transmission of Human Adenovirus Type 55 in Case of Fatal Acute Respiratory Disease.

We identified a case of fatal acute respiratory disease from household transmission of human adenovirus type 55 (HAdV-55) in Anhui Province, China. Computed tomography showed severe pneumonia. Comparative genomic analysis of HAdV-55 indicated the virus possibly originated in Shanxi Province, China. More attention should be paid to highly contagious HAdV-55.

Electrochemical N2 fixation by Cu-modified iron oxide dendrites.

The electrochemical nitrogen reduction reaction (NRR) under mild conditions is significantly challenging, due to the extremely high stability of dinitrogen (N2) molecules. The NRR pathway also confronts the competitive water reduction reaction that takes places universally in an aqueous solution. Herein, a Fe2O3/Cu catalyst is demonstrated as an efficient NRR electrocatalyst. The electronic interactions elevate the d-state electron center, enabling strong back-bonding for N2 molecules. The altering of d-electron distribution promotes the adsorption of N2, leading to a high catalytic activity. As a result, the Fe2O3/Cu catalyst exhibits an outstanding ammonia production rate of 15.66 µg·h-1·mgcat.-1 at -0.1 V versus reversible hydrogen electrode (RHE), a Faradaic efficiency of 24.4%, and a good electrochemical stability.

Molecular Characterization of Organics Removed by a Covalently Bound Inorganic-Organic Hybrid Coagulant for Advanced Treatment of Municipal Sewage.

Coagulation is an important process to remove organics from water. The molecular composition and structure of organic matter influence water quality in many ways, and the lack of information regarding the organics removed by different coagulants makes it challenging to optimize coagulation processes and ensure reclaimed water safety. In this paper, we investigated coagulation of secondary biological effluent from a municipal sewage treatment plant with different coagulants. We emphasized investigation of organics removal characteristics at the molecular level using Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS) coupled with electrospray ionization (ESI). We found that conventional coagulants can only partially remove condensed polycyclic aromatics and polyphenols with low H/C (H/C < 0.7) and highly unsaturated and phenolic compounds and aliphatic compounds with high O/C (O/C > 0.6). A new coagulant, CBHyC, had better removal efficiencies for all organics with different element compositions and molecular structures, especially organics that are resistant to conventional coagulants such as highly unsaturated and phenolic compounds and aliphatic compounds located in 0.3 < O/C < 0.8 and 1.0 < H/C < 2.0 regions and sulfur-containing compounds with higher O/C (e.g., anionic surfactants and their metabolites or coproducts). This study provides molecular insights into the organics removed by different coagulants and provides data supporting the possible optimization of advanced wastewater treatment processes.

Rapid Construction of a Replication-Competent Infectious Clone of Human Adenovirus Type 14 by Gibson Assembly.

In 1955, Human adenovirus type 14 (HAdV-B14p) was firstly identified in a military trainee diagnosed as acute respiratory disease (ARD) in the Netherlands. Fifty years later, a genomic variant, HAdV-B14p1, re-emerged in the U.S. and caused large and fatal ARD outbreaks. Subsequently, more and more ARD outbreaks occurred in Canada, the UK, Ireland, and China, in both military and civil settings. To generate a tool for the efficient characterization of this new genomic variant, a full-length infectious genomic clone of HAdV-B14 was successfully constructed using one-step Gibson Assembly method in this study. Firstly, the full genome of HAdV-B14p1 strain GZ01, the first HAdV-B14 isolate in China, was assembled into pBR322 plasmid by Gibson Assembly. The pBRAdV14 plasmid, generated by Gibson Assembly, was analyzed and verified by PCR, restriction enzymes digestion and the sequencing. Secondly, viruses were rescued from pBRAdV14-transfected A549 cells. The integrity of the rescued viruses was identified by restriction enzyme analysis. The complete sequence of the infectious clone was further sequenced. No mutation was found in the infectious clone during the construction when compared with the parental virus and pBR322 sequences. The direct immunofluorescence assay indicated the expression of the hexon protein. Finally, typical virions were observed; the one-step growth curves further showed that the DNA replication and viral reproduction efficiency of pBRAd14 derived viruses was similar with that of wild-type HAdV-B14 strain. The successful construction of the replication-competent infectious clone of pBRAdV14 facilitates the development of vaccine and antiviral drugs against HAdV-B14, as well as provides a novel strategy for rapid construction of infectious viral clones for other large-genome DNA viruses.

rs61991156 in miR-379 is associated with low capability of glycolysis of gastric cancer by enhanced regulation of PKM2.

BACKGROUND: Glycolysis is an important metabolic oncogenic change also play a pivot role in the Warburg effect. Glycolysis related gene PKM2 expressed differently individually. Presently, we sought to investigate the effect of single nucleotide polymorphism (SNP) at rs61991156 of miR-379 on gastric cancer (GC) proliferation and metabolism. METHODS: The genotype of rs61991156 in miR-379 was investigated by using real-time PCR. The glycolysis-related metabolites were determined by using GC-TOF-MS. The biological effects of rs61991156 in miR-379 was explored by in vitro studies. RESULTS: In this study, we found that rs61991156 in miR-379 was involved in the occurrence of GC by acting on the 3'UTR region of PKM2. The clinical data analysis revealed that A > G in rs187960998 was significantly associated with better differentiation, small tumor size, and non-metastasis. In vitro study further revealed that A > G SNP of miR-379 could decrease GC cell proliferation as well as the promoter activity and expression of PKM2. The glycolysis of the patients with miR-379 GG genotype was significantly lower than AG and AA genotype by metabolomics analysis. The patients with AA genotype have significantly lower PKM2 expression compared to the G carrier, while there is no significant expression difference in miR-379 expression. Patients with AA genotype have significantly shorter survival rate compared to the G carrier. CONCLUSION: rs61991156 in miR-379 was highly associated with a decreased risk, well differentiation and better post-surgery survival in Chinese population by inhibiting the expression of PKM2.

Comparative Genomic Analysis of Re-emergent Human Adenovirus Type 55 Pathogens Associated With Adult Severe Community-Acquired Pneumonia Reveals Conserved Genomes and Capsid Proteins.

Human adenovirus type 55 (HAdV-B55) is a recently identified acute respiratory disease (ARD) pathogen in HAdV species B with a recombinant genome between renal HAdV-B11 and respiratory HAdV-B14. Since HAdV-B55 first appeared in China school in 2006, no more ARD cases associated with it had been reported until 2011, when there was an outbreak of adult severe community-acquired pneumonia (CAP) in Beijing, China. Reported here is the bioinformatics analysis of the re-emergent HAdV-B55 responsible for this outbreak. Recombination and protein sequence analysis re-confirmed that this isolate (BJ01) was a recombinant virus with the capsid hexon gene from HAdV-B11. The selection pressures for the three capsid proteins, i.e., hexon, penton base, and fiber genes, were all negative, along with very low non-synonymous (dN) and synonymous (dS) substitutions/site (<0.0007). Phylogenetic analyses of the whole genome and the three major capsid genes of HAdV-B55 revealed the close phylogenetic relationship among all HAdV-B55 strains. Comparative genomic analysis of this re-emergent HAdV-B55 strain (BJ01; 2011) with the first HAdV-B55 strain (QS-DLL; 2006) showed the high genome identity (99.87%), including 10 single-nucleotide non-synonymous substitutions, 11 synonymous substitutions, 3 insertions, and one deletion in non-coding regions. The major non-synonymous substitutions (6 of 10) occurred in the protein pVI in its L3 region, which protein has different functions at various stages of an adenovirus infection, and may be associated with the population distribution of HAdV-B55 infection. No non-synonymous substitutions were found in the three major capsid proteins, which proteins are responsible for type-specific neutralizing antibodies. Comparative genomic analysis of the re-emergent HAdV-B55 strains associated with adult severe CAP revealed conserved genome and capsid proteins, providing the foundation for the development of effective vaccines against this pathogen. This study also facilitates the further investigation of HAdV-B55 epidemiology, molecular evolution, patterns of pathogen emergence and re-emergence, and the predication of genome recombination between adenoviruses.

Helicobacter pylori infection-induced H3Ser10 phosphorylation in stepwise gastric carcinogenesis and its clinical implications.

BACKGROUND: Our previous works have demonstrated that Helicobacter pylori (Hp) infection can alter histone H3 serine 10 phosphorylation status in gastric epithelial cells. However, whether Helicobacter pylori-induced histone H3 serine 10 phosphorylation participates in gastric carcinogenesis is unknown. We investigate the expression of histone H3 serine 10 phosphorylation in various stages of gastric disease and explore its clinical implication. MATERIALS AND METHODS: Stomach biopsy samples from 129 patients were collected and stained with histone H3 serine 10 phosphorylation, Ki67, and Helicobacter pylori by immunohistochemistry staining, expressed as labeling index. They were categorized into nonatrophic gastritis, chronic atrophic gastritis, intestinal metaplasia, low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia, and intestinal-type gastric cancer groups. Helicobacter pylori infection was determined by either 13 C-urea breath test or immunohistochemistry staining. RESULTS: In Helicobacter pylori-negative patients, labeling index of histone H3 serine 10 phosphorylation was gradually increased in nonatrophic gastritis, chronic atrophic gastritis, intestinal metaplasia groups, peaked at low-grade intraepithelial neoplasia, and declined in high-grade intraepithelial neoplasia and gastric cancer groups. In Helicobacter pylori-infected patients, labeling index of histone H3 serine 10 phosphorylation followed the similar pattern as above, with increased expression over the corresponding Helicobacter pylori-negative controls except in nonatrophic gastritis patient whose labeling index was decreased when compared with Helicobacter pylori-negative control. Labeling index of Ki67 in Helicobacter pylori-negative groups was higher in gastric cancer than chronic atrophic gastritis and low-grade intraepithelial neoplasia groups, and higher in intestinal metaplasia group compared with chronic atrophic gastritis group. In Helicobacter pylori-positive groups, Ki67 labeling index was increased stepwise from nonatrophic gastritis to gastric cancer except slightly decrease in chronic atrophic gastritis group. In addition, we noted that histone H3 serine 10 phosphorylation staining is accompanied with its location changes from gastric gland bottom expanded to whole gland as disease stage progress. CONCLUSIONS: These results indicate that stepwise gastric carcinogenesis is associated with altered histone H3 serine 10 phosphorylation, Helicobacter pylori infection enhances histone H3 serine 10 phosphorylation expression in these processes; it is also accompanied with histone H3 serine 10 phosphorylation location change from gland bottom staining expand to whole gland expression. The results suggest that epigenetic dysregulation may play important roles in Helicobacter pylori-induced gastric cancer.

Orally administered berberine ameliorates bleomycin-induced pulmonary fibrosis in mice through promoting activation of PPAR-γ and subsequent expression of HGF in colons.

Berberine has been demonstrated to alleviate renal interstitial, liver and myocardial fibrosis when administered orally despite its extremely low bioavailability. Here, we inspected effect of berberine on pulmonary fibrosis (PF) and explored underlying mechanisms on the basis of intestinal endocrine. The results showed that either oral or rectal administration of berberine exhibited marked alleviation of bleomycin-induced PF in mice. In contrast, anti-PF activity of berberine disappeared when given by an intravenous injection, implying that it functioned in a gut-dependent manner. Moreover, berberine promoted both mRNA and protein levels of HGF and PTEN in colons, but only their protein levels in lungs of PF mice. In addition, SU11274 but not BPV abolished the anti-PF effect of berberine. In vitro, berberine preferentially induced expression of HGF in fibroblast cells than epithelial, preadipocyte and endothelial cells. Similarly, rosiglitazone and 15dPGJ2 also enhanced expression of HGF in fibroblasts cells, and GW9662 and siPPAR-γ diminished induction of berberine on HGF expression. Berberine could enter into the cytoplasm, activate PPAR-γ directly and synergistically with 15dPGJ2, as shown by an up-regulation of CD36 and aP2 mRNA expression, nuclear translocation and DNA-binding activity of PPAR-γ both in vitro and in vivo. Additionally, GW9662 almost abolished anti-PF effect of berberine and induction of HGF expression in colons. In conclusion, oral administration of berberine displays anti-PF action probably in a colon-dependent manner, and mechanisms involve activation of PPAR-γ and resultant promotion of HGF expression in colonic fibroblasts. The up-regulated HGF arrives in lung tissues via blood circulation to palliate PF.

c-Abl regulates gastrointestinal muscularis propria homeostasis via ERKs.

The gastrointestinal tract is responsible for food digestion and absorption. The muscularis propria propels the foodstuff through the GI tract and defects in intestine motility may cause obstruction disorders. Our present genetic studies identified non-receptor tyrosine kinase c-Abl as an important regulator of the muscularis propria homeostasis and a risk factor for rectal prolapse. Mouse deficient for c-Abl showed defects in the muscularis propria of gastrointestinal tract and older c-Abl -/- mice developed megaesophagus and rectal prolapse. Inhibition of c-Abl with imatinib mesylate, an anti-CML drug, or ablation of c-Abl using Prx1-Cre, which marks smooth muscle cells, recapitulated most of the muscularis propria phenotypes. The pathogenesis of rectal prolapse was attributable to overproliferation of smooth muscle cells, which was caused by enhanced ERK1/2 activation. Administration of ERK inhibitor U0126 impeded the development of rectal prolapse in c-Abl deficient mice. These results reveal a role for c-Abl-regulated smooth muscle proliferation in the pathogenesis of rectal prolapse, and imply that long-term use of imatinib mesylate may cause gastrointestinal problems in patients while ERK inhibitor may be effective in treating rectal prolapse.