Artemisinin counteracts Edwardsiella tarda-induced liver inflammation and metabolic changes in juvenile fat greenling Hexagrammos otakii.

Emerging evidence suggests that artemisinin (ART) can modulate pathogen-induced immune responses and metabolic dysregulation. However, whether this modulation is associated with metabolic pathways related to oxidative stress and inflammation remains unclear. The aim of this study was to investigate the antioxidant and anti-inflammatory effects on the ART-fed juvenile fat greenling Hexagrammos otakii and the associated metabolic pathways in response to ART administration using an integrated biochemical and metabolomic approach. Biochemical analysis and histological examination showed that ART significantly increased body weight gain and improved tissue structure. ART effectively attenuated reactive oxygen species (ROS), malondialdehyde (MDA) and inflammatory responses (NFκB, TNF-α, IL-6, and MCP-1) in the Edwardsiella tarda-induced H. otakii model. Liver metabolomics analysis revealed that twenty-nine metabolites were up-regulated and twenty-one metabolites were down-regulated after ART administration compared to those in pathogen-induced fish. Pathway analysis indicated that ART alleviated the E. tarda-induced inflammation and oxidative stress through two major pathways, namely lipid metabolism and amino acid metabolism. Taken together, ART showed great potential as a natural feed additive against pathogen-induced oxidative stress and inflammation.

Use of Immunohistochemical p53 Mutant-Phenotype in Diagnosis of High-Grade Dysplasia of Esophageal Squamous Epithelia.

BACKGROUND: Mild cellular atypia of esophageal squamous epithelial dysplasia has a risk of progressing to cancer that poses great confusion for pathological diagnosis. There is no research on the diagnosis and differential diagnosis of esophageal squamous dysplasia by the expression of immunohistochemical (IHC) p53. The study aims to conduct a graded diagnosis of esophageal squamous epithelial hyperplasia by combining p53 expressions and microscopic histomorphological characteristics. METHODS: The study was conducted from January 2021 to January 2022 and included a total of 208 cases including 262 specimens with atypical hyperplasia or dysplasia of squamous epithelia discovered by esophageal mucosal biopsy. HE staining was used to grade the epithelial hyperplasia degree, and all cases underwent p53 IHC evaluation. RESULTS: Benign lesions: we did not find any p53 IHC mutant-phenotype (0/12 cases) in 12 cases of esophagitis. We found 10 cases (10/80 cases) of p53 IHC mutant-phenotype in 80 cases of low-grade dysplasia, and 158 cases (158/170 cases) of p53 IHC mutant-phenotype of high-grade lesions in 170 cases of high-grade dysplasia and early cancer based on the χ2 test results. We found statistically significant differences in p53 IHC mutant-phenotype between the high-grade squamous epithelial lesions and benign lesions. The sensitivity and specificity of p53 in detecting high-grade squamous epithelial lesions were 92.9% and 89.1%, respectively. The positive predictive value was 94.0%, and the negative predictive value was 87.2%. CONCLUSION: In this study, we found that p53 IHC had high sensitivity and specificity in detecting high-grade esophageal squamous epithelial lesions. Therefore, it has potential to be used as a routine item in pathological detection for auxiliary risk stratification of esophageal squamous epithelial lesions.

SNS-023 sensitizes hepatocellular carcinoma to sorafenib by inducing degradation of cancer drivers SIX1 and RPS16.

Hepatocellular carcinoma (HCC) remains challenging due to the lack of efficient therapy. Promoting degradation of certain cancer drivers has become an innovative therapy. The nuclear transcription factor sine oculis homeobox 1 (SIX1) is a key driver for the progression of HCC. Here, we explored the molecular mechanisms of ubiquitination of SIX1 and whether targeting SIX1 degradation might represent a potential strategy for HCC therapy. Through detecting the ubiquitination level of SIX1 in clinical HCC tissues and analyzing TCGA and GEPIA databases, we found that ubiquitin specific peptidase 1 (USP1), a deubiquitinating enzyme, contributed to the lower ubiquitination and high protein level of SIX1 in HCC tissues. In HepG2 and Hep3B cells, activation of EGFR-AKT signaling pathway promoted the expression of USP1 and the stability of its substrates, including SIX1 and ribosomal protein S16 (RPS16). In contrast, suppression of EGFR with gefitinib or knockdown of USP1 restrained EGF-elevated levels of SIX1 and RPS16. We further revealed that SNS-023 (formerly known as BMS-387032) induced degradation of SIX1 and RPS16, whereas this process was reversed by reactivation of EGFR-AKT pathway or overexpression of USP1. Consequently, inactivation of the EGFR-AKT-USP1 axis with SNS-032 led to cell cycle arrest, apoptosis, and suppression of cell proliferation and migration in HCC. Moreover, we showed that sorafenib combined with SNS-032 or gefitinib synergistically inhibited the growth of Hep3B xenografts in vivo. Overall, we identify that both SIX1 and RPS16 are crucial substrates for the EGFR-AKT-USP1 axis-driven growth of HCC, suggesting a potential anti-HCC strategy from a novel perspective.

Designed Fabrication of Phloretin-Loaded Propylene Glycol Binary Ethosomes: Stability, Skin Permeability and Antioxidant Activity.

Binary ethosome vesicles have been developed as flexible lipid vesicles for the enhanced physicochemical stability and skin delivery of drugs. This work aimed to prepare phloretin-loaded propylene glycol ethosomes (PHL-PGEs) to improve their stability, skin permeability and antioxidant activity. PHL-PGEs were prepared via the ethanol injection method and optimized using different weight ratios of ethanol to propylene glycol (PG). When the ethanol/PG mass ratio changed from 10:0 to 0:10, the encapsulation efficiency and stability of ethosomes increased. At a PHL concentration of 1mg/mL, the EE% was 89.42 ± 2.42 and the DL% was 4.21 ± 0.04, which exhibited their highest values. The encapsulation of the PHL in the PHL-PGEs was strengthened via XRD analysis and FTIR analysis. The results of the in vitro percutaneous permeability test demonstrated that the combined use of ethanol and PG exhibited a notable enhancement in skin permeability, and the skin retention of PHL-PGEs was 1.06 times that of PHL-ethosomes (PHL-Es) and 2.24 times that of the PHL solution. An in vitro antioxidant activity study indicated that solubility and antioxidant activity was potentiated via the nanoencapsulation of phloretin. Therefore, these results confirm the potential of this nanocarrier to enhance physicochemical stability, skin permeability and antioxidant activity.

Ras inhibitor farnesylthiosalicylic acid conjugated with IR783 dye exhibits improved tumor-targeting and altered anti-breast cancer mechanisms in mice.

Ras has long been viewed as a promising target for cancer therapy. Farnesylthiosalicylic acid (FTS), as the only Ras inhibitor has ever entered phase II clinical trials, has yielded disappointing results due to its strong hydrophobicity, poor tumor-targeting capacity, and low therapeutic efficiency. Thus, enhancing hydrophilicity and tumor-targeting capacity of FTS for improving its therapeutic efficacy is of great significance. In this study we conjugated FTS with a cancer-targeting small molecule dye IR783 and characterized the anticancer properties of the conjugate FTS-IR783. We showed that IR783 conjugation greatly improved the hydrophilicity, tumor-targeting and therapeutic potential of FTS. After a single oral administration in Balb/c mice, the relative bioavailability of FTS-IR783 was increased by 90.7% compared with FTS. We demonstrated that organic anion transporting polypeptide (OATP) and endocytosis synergistically drove the uptake of the FTS-IR783 conjugate in breast cancer MDA-MB-231 cells, resulting in superior tumor-targeting ability of the conjugate both in vitro and in vivo. We further revealed that FTS-IR783 conjugate could bind with and directly activate AMPK rather than affecting Ras, and subsequently regulate the TSC2/mTOR signaling pathway, thus achieving 2-10-fold increased anti-cancer therapeutic efficacy against 6 human breast cancer cell lines compared to FTS both in vivo and in vitro. Overall, our data highlights a promising approach for the modification of the anti-tumor drug FTS using IR783 and makes it possible to return FTS back to the clinic with a better efficacy.

Exosomes derived from stem cells from the apical papilla alleviate inflammation in rat pulpitis by upregulating regulatory T cells.

AIM: To evaluate the effects of exosomes derived from stem cells from the apical papilla (SCAP-Exos) in rats with experimentally induced pulpitis and the effects of SCAP-Exos on the conversion of regulatory T cells (Tregs) and methylation status of the Foxp3 locus in Tregs in vitro. METHODOLOGY: SCAP-Exos were isolated and identified using transmission electron microscopy, western blotting, and nanoparticle tracking analysis. Lipopolysaccharide was used to experimentally induced pulpitis in rats, and the effects of SCAP-Exos on the rats with pulpitis were detected using haematoxylin-eosin staining and immunofluorescence staining. CD4+ CD25- T cells were treated with different doses of SCAP-Exos, and flow cytometric analysis was used to assess the effects of SCAP-Exos on Treg proliferation and conversion. An enzyme-linked immunosorbent assay (ELISA) was used to evaluate the expression of interleukin 10 (IL-10). MethylTarget® technology was used to measure the methylation level of the Foxp3 locus in T cells. The expression levels of ten-eleven-translocation (Tet) 1, Tet2, and Tet3 in T cells were detected by real-time PCR and western blotting. RESULTS: SCAP-Exos had an elliptical vesicle-like structure with a diameter of approximately 143.7 nm and expressed the exosomal markers Alix and CD9. SCAP-Exo administration increased Treg accumulation in the inflamed dental pulp and alleviated inflammation in the dental pulp in vivo. SCAP-Exos promoted Treg conversion in vitro. Mechanistically, SCAP-Exos promoted Tet2-mediated Foxp3 demethylation to maintain the stable expression of Foxp3. CONCLUSIONS: SCAP-Exos promoted Treg conversion and effectively alleviated inflammation in the dental pulp of rats. This study shows that SCAP-Exos can regulate the local immune microenvironment to favour tissue regeneration, thus providing a potential novel strategy utilising SCAP-Exos as a cell-free approach to treat early inflammation of dental pulp in immature permanent teeth in the clinic.

The rapid identification of chemical constituents in Fufang Xiling Jiedu capsule, a modern Chinese medicine, by ultra-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry and data mining strategy.

Fufang Xiling Jiedu capsule is an effective Chinese medicine widely used for the treatment of cold and influenza. However, its chemical constituents had not been determined, which entailed a huge obstacle to further pharmacological studies, clinical-safe medication administration, and quality evaluation. To identify the chemical constituents in Fufang Xiling Jiedu capsule, an efficient and systematic approach using ultra-high-performance liquid chromatography coupled with a quadrupole time-of-flight mass spectrometry in conjunction with a data mining strategy was adopted in this study. As a result, 145 compounds were qualitatively identified, including 26 phenolic acids, 46 flavonoids, 39 triterpenes, and 34 other compounds, among which 6 were potentially new and 144 were being reported from Fufang Xiling Jiedu capsule for the first time. This research not only provides useful information for quality control of Fufang Xiling Jiedu capsule and its involved single herbs but also serve as basis data for further study of Fufang Xiling Jiedu capsule in vivo. Moreover, it provides a reference for the characterization of the chemical constituents of other Chinese medicine preparations.

Evaluation of conditioned medium from placenta-derived mesenchymal stem cells as a storage medium for avulsed teeth: An in vitro study.

BACKGROUND/AIM: The viability of periodontal ligament cells on the root surface is a major factor that influences the healing of replanted teeth. A suitable storage medium is necessary to preserve avulsed teeth before replantation. Conditioned medium from placenta-derived mesenchymal stem cells (PMSC-CM) contains a variety of growth factors. The aim of this study was to evaluate the effectiveness of PMSC-CM as a storage medium to maintain the cell viability of avulsed teeth. MATERIAL AND METHODS: Extracted premolars from healthy humans were randomly stored in Hank's balanced salt solution (HBSS) and PMSC-CM for 6, 12 and 24 hours, respectively, at room temperature, and then the ratio of apoptosis of the periodontal ligament (PDL) cells was identified by flow cytometry. Human periodontal ligament stem cells (PDLSCs) were incubated with HBSS and PMSC-CM, respectively, for 6, 12, 24 and 48 hours in 5% CO2 at 37°C. Then, the cell viability of PDLSCs was determined using the cell counting kit-8 (CCK-8) and a cell cycle assay was performed. RESULTS: The apoptosis rate of PDL cells in PMSC-CM was significantly lower than that in HBSS at 24 hours (P < .001), while the two groups showed similar cell apoptosis rates at 6 and 12 hours (P > .05). The cell proliferation of PDLSCs treated with PMSC-CM significantly increased compared with the HBSS group (P < .05). The cell cycle assay revealed that the PDLSCs treated with HBSS were arrested at the G1 phase, while there was no difference between the PMSC-CM group and the control group (P > .05). CONCLUSIONS: Compared with HBSS, PMSC-CM showed better inhibition of apoptosis of PDL cells and promoted the proliferation of PDLSCs. Thus, PMSC-CM could be a promising storage medium for avulsed teeth.

Avian Influenza Virus Detection Rates in Poultry and Environment at Live Poultry Markets, Guangdong, China.

We report the use of environmental samples to assess avian influenza virus activity in chickens at live poultry markets in China. Results of environmental and chicken samples correlate moderately well. However, collection of multiple environmental samples from holding, processing, and selling areas is recommended to detect viruses expected to have low prevalence.

Genetic diversity and ex situ conservation of Loropetalum subcordatum, an endangered species endemic to China.

BACKGROUND: Loropetalum subcordatum is an endangered species endemic to China that is characterized by narrow distribution, small population size, and delayed fertilization. However, the genetic diversity of the entire extant natural and ex situ populations has not been assessed to date. In this study, we evaluated the genetic diversity and structure of six natural populations and a single ex situ population (the only known ex situ population of L. subcordatum) using sequence-related amplified polymorphism data. RESULTS: In total, 553 reliable DNA bands, of which 359 (63.28%) were polymorphic, were amplified by polymerase chain reaction with combinations of 15 primers. Low average gene diversity within populations and high genetic differentiation were detected in L. subcordatum. A Mantel test demonstrated that there was a positive correlation between genetic and geographic distances, indicating that significant genetic divergence was likely the result of geographic isolation among natural populations. Furthermore, based on genetic structure patterns, populations of L. subcordatum were divided into three clusters. Group 1 was composed of specimens from Libo, Guizhou Province (GZ) and Huanjiang, Guangxi Zhuang Autonomous Region (GX). Group 2 was composed of Mt. Wuguishan, Guangdong Province (GD). Group 3 was composed of three populations in Hong Kong Special Administrative Region. Additionally, clonal reproduction probably existed in GD population. According to the genetic information analysis and field survey, the ex situ population did not match its source population (GD) in terms of genetics, and its habitat was different from the original natural habitat. We observed that a few individual GD seeds were needed to improve ZS ex situ in the future. CONCLUSIONS: Compared to previous SRAP-based studies of endangered plants, L. subcordatum had extremely low average gene diversity within populations and high genetic differentiation among populations. At present, the unique ex situ population has not been successful due to non-representative samples being taken, a smaller population size, and man-made changes in habitat. Potential strategies are suggested to improve the conservation of this species.

A molecular phylogeny of Aeridinae (Orchidaceae: Epidendroideae) inferred from multiple nuclear and chloroplast regions.

The subtribe Aeridinae, which contains approximately 90 genera, is one of the most diverse and taxonomically puzzling groups in Orchidaceae. In the present study, the phylogenetic relationships of Aeridinae were reconstructed utilizing five DNA sequences (ITS, atpI-H, matK, psbA-trnH, and trnL-F) from 211 taxa in 74 genera. The results of the phylogenetic analyses indicate that Aeridinae is monophyletic and that the subtribe can primarily be grouped into 10 clades: (1) Saccolabium clade, (2) Chiloschista clade, (3) Phalaenopsis clade, (4) Thrixspermum clade, (5) Vanda clade, (6) Aerides clade, (7) Trichoglottis clade, (8) Abdominea clade, (9) Gastrochilus clade, and (10) Cleisostoma clade. In our examination, most genera of Aeridinae were well-supported as monophyletic, and several genera, namely, Pteroceras, Cleisostoma, Vandopsis, Diploprora, Malleola, and Robiquetia, were found to be polyphyletic as currently circumscribed. In addition, several classifications of intra-genera, such as the subgenus Codonosepalum of Taeniophyllum and the section Gastrochilus of Gastrochilus, were also revealed to be paraphyletic. Due to the many questions raised by our phylogenies, the present study may serve as a reference for future taxonomic studies of Aeridinae.

Cloning and expression analysis of a novel high-mobility group box 2 homologue from Lampetra japonica.

High-mobility group box 2 (HMGB2) is a nonhistone architectural protein that plays important roles in many biological processes. In this study, we cloned a homologue of the HMGB2 from the lymphocyte-like cells of Lampetra japonica (L. japonica). Sequence analysis reveals that L. japonica HMGB2 contains two highly conserved motifs and shares more than 70 % identity with the homologues from other vertebrate species. Subsequently, Lj-HMGB2 was subcloned into the pET-28a(+) and pIRES2 AcGFP1-Nuc vector and expressed in Rosetta blue (DE3) and Hela cell lines, respectively. The recombinant L. japonica HMGB2 (rLj-HMGB2) with apparent molecular mass of 22 kDa was further purified by His-Bind affinity chromatography. Real-time quantitative PCR indicates that the expression level of Lj-HMGB2 was particularly up-regulated in intestines after challenged with lipopolysaccharide, while up-regulated in lymphocyte-like cells and heart after challenged with concanavalin A in vivo. In addition, rLj-HMGB2 could induce the generation of proinflammatory mediators in the activated human acute monocytic leukemia cell line (THP1), which suggested that Lj-HMGB2 may participate in the immune response of the lampreys.

SIAH2 is specifically expressed during cervical carcinogenesis, and closely relates to the abnormal proliferation of cervical epithelial cells.

Background: Cervical cancer is one of the most common malignancies in women worldwide. As a RING type ubiquitin ligase, SIAH2 has been reported to promote the progression of a variety of tumors by interacting with and targeting multiple chaperones and substrates. The aim of this study was to further identify the role and the related molecular mechanisms involved of SIAH2 in cervical carcinogenesis. Methods and results: Cellular assays in vitro showed that knockdown of SIAH2 inhibited the proliferation, migration and invasion of human cervical cancer cells C33A and SiHa, induced apoptosis, and increased the sensitivity to cisplatin treatment. Knockdown of SIAH2 also inhibited the epithelial-mesenchymal transition and activation of the Akt/mTOR signaling pathway in cervical cancer cells, which were detected by Western blot. Mechanistically, SIAH2, as a ubiquitin ligase, induced the ubiquitination degradation of GSK3ß degradation by using coIP. The results of complementation experiments further demonstrated that GSK3ß overexpression rescued the increase of cell proliferation and invasion caused by SIAH2 overexpression. Specific expression of SIAH2 appeared in precancerous and cervical cancer tissues compared to inflammatory cervical lesions tissues using immunohistochemical staining. The more SIAH2 was expressed as the degree of cancer progressed. SIAH2 was significantly highly expressed in cervical cancer tissues (44/55, 80 %) compared with precancerous tissues (18/69, 26.1 %). Moreover, the expression level of SIAH2 in cervical cancer tissues was significantly correlated with the degree of cancer differentiation, and cervical cancer tissues with higher SIAH2 expression levels were less differentiated. Conclusion: Targeting SIAH2 may be beneficial to the treatment of cervical cancer.

Synthesis, characterization, and efficacy evaluation of a PH-responsive Fe-MOF@GO composite drug delivery system for the treating colorectal cancer.

Luteolin is a potent anti-colorectal cancer chemical. However, its effectiveness is hindered by its poor solubility in water and fat, and it is easy to degrade by gastrointestinal enzymes. In this study, a nano-composite carrier, NH2-MIL-101(Fe)@GO (MG), based on aminated MIL-101(Fe) and graphene oxide (GO) was developed and evaluated. This carrier co-delivered luteolin and matrine, while marine was used to balance the pH for the nano-preparation. The loading capacities for luteolin and matrine were approximately 9.8% and 14.1%, respectively. Luteolin's release at pH = 5 was significantly higher than at pH = 7.4, indicating it had an acidic pH response release characteristic. Compared to MOF and GO alone, MG and NH2-MIL-101(Fe)@GO@Drugs (MGD) enhanced anti-cancer activity by inhibiting tumor cell migration, increasing ROS generation, and upregulating the expression of Caspase-3 and Caspase-9. In conclusion, this study contributes new ideas and methods to the treatment strategy of multi-component anti-colorectal cancer therapy. It also advances drug delivery systems and supports the development of more effective and targeted treatment approaches for colorectal cancer.

Enhanced immunity against SARS-CoV-2 in returning Chinese individuals.

Global COVID-19 vaccination programs effectively contained the fast spread of SARS-CoV-2. Characterizing the immunity status of returned populations will favor understanding the achievement of herd immunity and long-term management of COVID-19 in China. Individuals were recruited from 7 quarantine stations in Guangzhou, China. Blood and throat swab specimens were collected from participants, and their immunity status was determined through competitive ELISA, microneutralization assay and enzyme-linked FluoroSpot assay. A total of 272 subjects were involved in the questionnaire survey, of whom 235 (86.4%) were returning Chinese individuals and 37 (13.6%) were foreigners. Blood and throat swab specimens were collected from 108 returning Chinese individuals. Neutralizing antibodies against SARS-CoV-2 were detected in ~90% of returning Chinese individuals, either in the primary or the homologous and heterologous booster vaccination group. The serum NAb titers were significantly decreased against SARS-CoV-2 Omicron BA.5, BF.7, BQ.1 and XBB.1 compared with the prototype virus. However, memory T-cell responses, including specific IFN-γ and IL-2 responses, were not different in either group. Smoking, alcohol consumption, SARS-CoV-2 infection, COVID-19 vaccination, and the time interval between last vaccination and sampling were independent influencing factors for NAb titers against prototype SARS-CoV-2 and variants of concern. The vaccine dose was the unique common influencing factor for Omicron subvariants. Enhanced immunity against SARS-CoV-2 was established in returning Chinese individuals who were exposed to reinfection and vaccination. Domestic residents will benefit from booster homologous or heterologous COVID-19 vaccination after reopening of China, which is also useful against breakthrough infection.

Clinical study of NFNC in the treatment of acute exacerbation chronic obstructive pulmonary disease patients with respiratory failure.

BACKGROUND: Most patients with acute exacerbation chronic obstructive pulmonary disease (AECOPD) have respiratory failure that necessitates active correction and the improvement of oxygenation is particularly important during treatment. High flow nasal cannula (HFNC) oxygen therapy is a non-invasive respiratory aid that is widely used in the clinic that improves oxygenation state, reduces dead space ventilation and breathing effort, protects the loss of cilia in the airways, and improves patient comfort. AIM: To compare HFNC and non-invasive positive pressure ventilation in the treatment of patients with AECOPD. METHODS: Eighty AECOPD patients were included in the study. The patients were in the intensive care department of our hospital from October 2019 to October 2021. The patients were divided into the control and treatment groups according to the different treatment methods with 40 patients in each group. Differences in patient comfort, blood gas analysis and infection indices were analyzed between the two groups. RESULTS: After treatment, symptoms including nasal, throat and chest discomfort were significantly lower in the treatment group compared to the control group on the 3rd and 5th days (P < 0.05). Before treatment, the PaO2, PaO2/FiO2, PaCO2, and SaO2 in the two groups of patients were not significantly different (P > 0.05). After treatment, the same indicators were significantly improved in both patient groups but had improved more in the treatment group compared to the control group (P < 0.05). After treatment, the white blood cell count, and the levels of C-reactive protein and calcitonin in patients in the treatment group were significantly higher compared to patients in the control group (P < 0.05). CONCLUSION: HFNC treatment can improve the ventilation of AECOPD patients whilst also improving patient comfort, and reducing complications. HFNC is a clinically valuable technique for the treatment of AECOPD.

Ethanol mediates the interaction between Caenorhabditis elegans and the nematophagous fungus Purpureocillium lavendulum.

Accurately recognizing pathogens by the host is vital for initiating appropriate immune response against infecting microorganisms. Caenorhabditis elegans has no known receptor to recognize pathogen-associated molecular pattern. However, recent studies showed that nematodes have a strong specificity for transcriptomes infected by different pathogens, indicating that they can identify different pathogenic microorganisms. However, the mechanism(s) for such specificity remains largely unknown. In this study, we showed that the nematophagous fungus Purpureocillium lavendulum can infect the intestinal tract of the nematode C. elegans and the infection led to the accumulation of reactive oxygen species (ROS) in the infected intestinal tract, which suppressed fungal growth. Co-transcriptional analysis revealed that fungal genes related to anaerobic respiration and ethanol production were up-regulated during infection. Meanwhile, the ethanol dehydrogenase Sodh-1 in C. elegans was also up-regulated. Together, these results suggested that the infecting fungi encounter hypoxia stress in the nematode gut and that ethanol may play a role in the host-pathogen interaction. Ethanol production in vitro during fungal cultivation in hypoxia conditions was confirmed by gas chromatography-mass spectrometry. Direct treatment of C. elegans with ethanol elevated the sodh-1 expression and ROS accumulation while repressing a series of immunity genes that were also repressed during fungal infection. Mutation of sodh-1 in C. elegans blocked ROS accumulation and increased the nematode's susceptibility to fungal infection. Our study revealed a new recognition and antifungal mechanism in C. elegans. The novel mechanism of ethanol-mediated interaction between the fungus and nematode provides new insights into fungal pathogenesis and for developing alternative biocontrol of pathogenic nematodes by nematophagous fungi. IMPORTANCE Nematodes are among the most abundant animals on our planet. Many of them are parasites in animals and plants and cause human and animal health problems as well as agricultural losses. Studying the interaction of nematodes and their microbial pathogens is of great importance for the biocontrol of animal and plant parasitic nematodes. In this study, we found that the model nematode Caenorhabditis elegans can recognize its fungal pathogen, the nematophagous fungus Purpureocillium lavendulum, through fungal-produced ethanol. Then the nematode elevated the reactive oxygen species production in the gut to inhibit fungal growth in an ethanol dehydrogenase-dependent manner. With this mechanism, novel biocontrol strategies may be developed targeting the ethanol receptor or metabolic pathway of nematodes. Meanwhile, as a volatile organic compound, ethanol should be taken seriously as a vector molecule in the microbial-host interaction in nature.

[Value of soluble transferrin receptor in the diagnosis of iron deficiency in children].

OBJECTIVE: To study the prevalence of iron deficiency in children between 6 months and 7 years and to study the diagnostic value of soluble transferrin receptor (sTfR) for iron deficiency in the children. METHODS: A total of 502 healthy children between 6 months and 7 years from Hangzhou City of Zhejiang Province were enrolled. Serum sTfR, serum ferritin (SF), serum iron (SI), total iron blinding capacity (TIBC), zinc protoporphyrin (ZPP), Hb, MCV and CRP levels were measured. RESULTS: The prevalence rate of iron deficiency was 19.5% in children at ages of 6 months to 7 years. The prevalence rate of iron deficiency was the highest in infants (≤1 year old; 34.7%), followed by in toddlers (1-3 years old; 19.4%) and preschoolers (3-7 years old; 14.0%). The mean serum sTfR level in infants (2.02±0.73 mg/L) was significantly higher than that in toddlers (1.68±0.40 mg/L) and preschoolers (1.67±0.29 mg/L) (P<0.05).The best cut-off value of serum sTfR for the diagnosis of iron deficiency was 2.02 mg/L in infants (sensitivity: 70.3%, specificity: 82.2%). The best cut-off value was 1.85 mg/L in toddlers (sensitivity: 71.7%; specificity: 86.4%), and that was 1.85 mg/L in preschoolers (sensitivity: 77.8%; specificity: 88.6%). Serum sTfR was correlated with SF (r=0.107, P<0.05), TIBC (r=0.276, P<0.01), TS (r=-0.139, P<0.05), ZPP (r=0.175, P<0.01) and MCV (r=-0.140, P<0.01). CONCLUSIONS: Iron deficiency is more prevalent in infants ≤1 year old. The mean serum level and the cut-off value of sTfR in infants are higher than in toddlers and preschoolers. Serum sTfR is an effective index for the diagnosis of iron deficiency in children, especially in infants≤ 1 year old.

Adenovirus infection in children hospitalized with pneumonia in Guangzhou, China.

BACKGROUND: HAdV infection can cause a variety of diseases. Although infections with HAdVs often are mild, life-threatening respiratory disease can occur. Pneumonia is one of the more serious types of HAdV-induced respiratory disease in children. In this study, we determined the prevalence and genotype of HAdVs among children hospitalized with pneumonia in Guangzhou, China. METHODS: Nasopharyngeal swabs (NPSs) were collected from children hospitalized with pneumonia in Guangzhou, China, from January 2013 to June 2019. HAdVs were detected by real-time polymerase chain reaction assay, and hexon, fiber, and penton gene were amplified and used for phylogenetic analysis. Epidemiological data were analyzed using SPSS16.0 software. RESULTS AND CONCLUSIONS: A total of 1778 children hospitalized with pneumonia were enrolled. The overall HAdV detection rate was 3.26%. And the yearly detection rate varied from around 2.5% in 2013-2017 to around 6% in 2018-2019. Children >5 years had the highest HAdV infection rate. 92.86% of HAdV sequences obtained in this study were belonged to species B, and no recombination was observed. HAdV-B7 and HAdV-B3 were the common types detected in the study period, with the predominant HAdV genotype shifted from HAdV-B3 in 2015-2016 to HAdV-B7 in 2017-2018. The discrepancies in HAdV detection rates in different study period and changes of HAdV predominant types over time highlighted the importance of continued surveillance.

Interleukin 18 and interleukin 18 binding protein in patients with idiopathic thrombocytopenic purpura.

To evaluate the balance of interleukin IL18 and its endogenous antagonist IL18 binding protein (IL18BP) in patients with idiopathic thrombocytopenic purpura (ITP), plasma IL18, IL18BP, interferon gamma (IFNG) and IL4 levels, as well as platelet counts were measured in patients with active ITP (n = 23), ITP in remission (n = 21) and in healthy subjects (n = 24) by enzyme linked immunosorbent assay (ELISA). Using real-time quantitative polymerase chain reaction, the mRNA expression of IL18, IL18BP, IFNG, IL4, T-box (TBX21) and GATA-binding protein 3(GATA3) were studied in all subjects. The results showed that IL18 and IFNG protein and mRNA levels were significantly increased in patients with active ITP than in control subjects, but that IL18BP were not significantly elevated in ITP patients, which resulted in an elevated ratio of IL18/IL18BP in patients with active disease. During remission stages, the levels of these cytokines were comparable to those of healthy controls. The elevated levels of IL18/IL18BP in plasma during active stages of disease suggest a possible role in the pathogenesis and course of ITP.