Modulation of host lipid metabolism by virus infection leads to exoskeleton damage in shrimp.

The arthropod exoskeleton provides protection and support and is vital for survival and adaption. The integrity and mechanical properties of the exoskeleton are often impaired after pathogenic infection; however, the detailed mechanism by which infection affects the exoskeleton remains largely unknown. Here, we report that the damage to the shrimp exoskeleton is caused by modulation of host lipid profiles after infection with white spot syndrome virus (WSSV). WSSV infection disrupts the mechanical performance of the exoskeleton by inducing the expression of a chitinase (Chi2) in the sub-cuticle epidermis and decreasing the cuticle chitin content. The induction of Chi2 expression is mediated by a nuclear receptor that can be activated by certain enriched long-chain saturated fatty acids after infection. The damage to the exoskeleton, an aftereffect of the induction of host lipogenesis by WSSV, significantly impairs the motor ability of shrimp. Blocking the WSSV-caused lipogenesis restored the mechanical performance of the cuticle and improved the motor ability of infected shrimp. Therefore, this study reveals a mechanism by which WSSV infection modulates shrimp internal metabolism resulting in phenotypic impairment, and provides new insights into the interactions between the arthropod host and virus.

NFKBIZ regulates NFκB signaling pathway to mediate tumorigenesis and metastasis of hepatocellular carcinoma by direct interaction with TRIM16.

Hepatocellular carcinoma (HCC) is a malignant tumor with high incidence and mortality rates. NFKBIZ, a member of the nuclear factor kappa B inhibitory family, is closely related to tumor progression. However, the precise role of NFKBIZ in HCC remains unclear. To explore this, we conducted a series of experiments from clinic to cells. Western blot and qPCR revealed a significant downregulation of NFKBIZ in human HCC tissues. Clinical character analysis showed that the patients with lower NFKBIZ expression had poorer prognosis and higher clinical stage. By using CCK-8, wound healing, transwell invasion and migration assay, we discovered that NFKBIZ expression was reversely associated with the proliferation, invasion, and migration ability of HCC cells in vitro. Additionally, the results obtained from xenograft assay and lung metastasis models showed that NFKBIZ overexpression inhibited the growth and metastasis of HCC cells in vivo. Western blot and immunofluorescence assay further revealed that NFKBIZ mediated HCC cell growth and migration by regulating NFκB signaling transduction. Finally, flow cytometry, protein degradation assay and Co-immunoprecipitation indicated that TRIM16 can enhance NFKBIZ ubiquitination by direct interactions at its K48 site, which may thereby alleviate HCC cell apoptosis to induce the insensitivity to sorafenib. In conclusion, our study demonstrated that NFKBIZ regulated HCC tumorigenesis and metastasis by mediating NFκB signal transduction and TRIM16/NFKBIZ/NFκB axis may be the underlying mechanism of sorafenib insensitivity in HCC.

Regulator of G-protein signaling 14 protects the liver from ischemia-reperfusion injury by suppressing TGF-ß-activated kinase 1 activation.

BACKGROUND AND AIMS: Hepatic ischemia-reperfusion injury (IRI) is a common complication of hepatectomy and liver transplantation. However, the mechanisms underlying hepatic IRI have not been fully elucidated. Regulator of G-protein signaling 14 (RGS14) is a multifunctional scaffolding protein that integrates the G-protein and mitogen-activated protein kinase (MAPK) signaling pathways. However, the role of RGS14 in hepatic IRI remains unclear. APPROACH AND RESULTS: We found that RGS14 expression increased in mice subjected to hepatic ischemia-reperfusion (IR) surgery and during hypoxia reoxygenation in hepatocytes. We constructed global RGS14 knockout (RGS14-KO) and hepatocyte-specific RGS14 transgenic (RGS14-TG) mice to establish 70% hepatic IRI models. Histological hematoxylin and eosin staining, levels of alanine aminotransferase and aspartate aminotransferase, expression of inflammatory factors, and apoptosis were used to assess liver damage and function in these models. We found that RGS14 deficiency significantly aggravated IR-induced liver injury and activated hepatic inflammatory responses and apoptosis in vivo and in vitro. Conversely, RGS14 overexpression exerted the opposite effect of the RGS14-deficient models. Phosphorylation of TGF-ß-activated kinase 1 (TAK1) and its downstream effectors c-Jun N-terminal kinase (JNK) and p38 increased in the liver tissues of RGS14-KO mice but was repressed in those of RGS14-TG mice. Furthermore, inhibition of TAK1 phosphorylation rescued the effect of RGS14 deficiency on JNK and p38 activation, thus blocking the inflammatory responses and apoptosis. CONCLUSIONS: RGS14 plays a protective role in hepatic IR by inhibiting activation of the TAK1-JNK/p38 signaling pathway. This may be a potential therapeutic strategy for reducing incidences of hepatic IRI in the future.

E3 ubiquitin ligase ring finger protein 5 protects against hepatic ischemia reperfusion injury by mediating phosphoglycerate mutase family member 5 ubiquitination.

BACKGROUND AND AIMS: Hepatic ischemia-reperfusion (HIR) injury, a common clinical complication of liver transplantation and resection, affects patient prognosis. Ring finger protein 5 (RNF5) is an E3 ubiquitin ligase that plays important roles in endoplasmic reticulum stress, unfolded protein reactions, and inflammatory responses; however, its role in HIR is unclear. APPROACH AND RESULTS: RNF5 expression was significantly down-regulated during HIR in mice and hepatocytes. Subsequently, RNF5 knockdown and overexpression of cell lines were subjected to hypoxia-reoxygenation challenge. Results showed that RNF5 knockdown significantly increased hepatocyte inflammation and apoptosis, whereas RNF5 overexpression had the opposite effect. Furthermore, hepatocyte-specific RNF5 knockout and transgenic mice were established and subjected to HIR, and RNF5 deficiency markedly aggravated liver damage and cell apoptosis and activated hepatic inflammatory responses, whereas hepatic RNF5 transgenic mice had the opposite effect compared with RNF5 knockout mice. Mechanistically, RNF5 interacted with phosphoglycerate mutase family member 5 (PGAM5) and mediated the degradation of PGAM5 through K48-linked ubiquitination, thereby inhibiting the activation of apoptosis-regulating kinase 1 (ASK1) and its downstream c-Jun N-terminal kinase (JNK)/p38. This eventually suppresses the inflammatory response and cell apoptosis in HIR. CONCLUSIONS: We revealed that RNF5 protected against HIR through its interaction with PGAM5 to inhibit the activation of ASK1 and the downstream JNK/p38 signaling cascade. Our findings indicate that the RNF5-PGAM5 axis may be a promising therapeutic target for HIR.

Impact of Al2O3 doping on Bi active center photobleaching in Bi/Er-codoped fibers.

In this Letter, the impact of Al2O3 doping on the Bi active center (BAC) photobleaching is investigated in Bi/Er-codoped fibers (BEDFs). By measuring the evolution of emission attributed to the BAC associated with silica (BAC-Si) at ∼1400nm, the linear relationship between the ratio of unbleached/bleached part (γUB/γB) and 830 nm irradiation intensity (P830) was revealed in the log-log plot. The experimental results demonstrate that Al2O3 doping or its induced defects could be one key factor exaggerating the BAC photobleaching in BEDFs.

Thermally aggravated photo-bleaching of BAC-Al in bismuth/erbium co-doped optical fiber.

The thermal effect upon the photo-bleaching of bismuth/erbium co-doped optical fiber (BEDF) containing Al has been investigated. The photo-bleaching effects of aluminum related bismuth active center (BAC-Al) in BEDF are studied from room temperature (RT) up to 350°C under the irradiation of a 980 nm laser. No visible bleaching of the luminescence associated with BAC-Al was observed at RT, but significant bleaching appeared at higher temperatures above 150°C under the same irradiation power. The underlying mechanism of significant thermal aggravation of photo-bleaching is discussed, and its impact needs to be considered in the design and application of optical amplifiers and lasers using Al-doped BEDF.

Seroprevalence of diphtheria and pertussis immunoglobulin G among children with pneumonia in Ji'nan, China.

BACKGROUND: Vaccination is still one of the most important methods to control and prevent childhood infections including diphtheria and pertussis. This study evaluated the level of diphtheria (DT) and pertussis (PT)-related antibodies among children with pneumonia in Ji'nan, China. METHODS: A total of 484 sera of children from 1 day to 13 years of age were collected from 2014 to 2015 in Ji'nan. Children with recent history of pertussis were excluded from this study. Anti-DT and PT IgG concentrations were measured by ELISA (Euroimmun, Lübeck, Germany). RESULTS: Of the 484 subjects tested, the overall positivity rate of anti-DT IgG (≥0.1 IU/ml) was 48.97%, and the highest positivity rate of anti-DT IgG (68.55%) and proportion with long term protection (23.27%) were observed in children aged 6 m- < 3 y. For anti-PT IgG, 334 subjects (69.01%) had anti-PT IgG levels below the lower limit of detection (5 IU/ml). Even with detectable anti-PT antibodies, the majority (115/150, 76.67%) of them had antibody levels of 5- < 40 IU/ml. The highest proportion of subjects with detectable anti-PT IgG (≥5 IU/ml) was observed in children aged < 6 m (44.36%), then the proportion continually decreased to 15.0% at 3 y- < 6 y (χ2 = 24.05, p < 0.0001). The highest positivity rate (≥40 IU/ml) was only 8.27% in children aged < 6 m. Subjects with an anti-PT IgG ≥100 IU/ml were observed in all the groups and there were no significant differences in the proportions of subjects with a level ≥ 100 IU/ml among these age groups (χ2 = 2.572, p = 0.4624). A total of 5 subjects had anti-PT IgG ≥100 IU/ml (≥1 years post pertussis vaccination) which was considered to be indicative of a recent pertussis infection. CONCLUSIONS: We demonstrated low antibody levels and protection against pertussis in our study population. The anti-PT IgG maintained a low level throughout all age groups, and even no immune responses were observed after the basic immunization and booster. Our study supported the need to reevaluate the immune response of DTP vaccine which was used in Shandong province after 2010.

Photo-bleaching mechanism of the BAC-Si in bismuth/erbium co-doped optical fibers.

Photo-bleaching of the silica-related bismuth active center (BAC-Si) in bismuth/erbium co-doped optical fibers is investigated. By analyzing dynamic spectral characteristics of BAC-Si, the photo-bleaching of the BAC-Si is found to be linked to the escape of an excited electron from the bismuth site in the BAC-Si. This mechanism of BAC-Si bleaching linked to an escaping excited electron is further confirmed with both photo-bleaching experiments by different laser pump wavelengths and a potential energy model describing the loss of an excited electron. Additionally, the temperature effect on the photo-bleaching, which is in good agreement with the above findings, is observed and discussed.

Reversible photo-bleaching effect in a bismuth/erbium co-doped optical fiber under 830 nm irradiation.

We observed photo-bleaching in a bismuth/erbium co-doped optical fiber (BEDF) under 830 nm irradiation. As a result of the photo-bleaching, the absorption at 814 nm and the near-infrared luminescence at 1420 nm are decreased, indicating that the silicon-based bismuth active center (BAC-Si) in a BEDF is bleached in the process. We further found that the photo-bleaching is reversible under room temperature. This is the first time that the BAC-Si could be bleached under 830 nm irradiation, and the photo-bleaching is reversible. The underlying mechanism of the reversible photo-bleaching effect is discussed.

Discriminative strain and temperature measurement using Brillouin scattering and fluorescence in erbium-doped optical fiber.

We develop a novel discriminative sensing technique of strain and temperature using Brillouin scattering and fluorescence in an erbium-doped fiber (EDF). First, we show that the fluorescence intensity ratio (FIR), the ratio of the fluorescence intensities at two different wavelengths (1530 nm and 1565 nm in this experiment), is linearly dependent on temperature (with a coefficient of 5.6 × 10⁻4 /°C) but almost independent of strain. Then, by combined use of the FIR and the Brillouin frequency shift in an EDF, we experimentally demonstrate discriminative measurements of strain and temperature with four different sets of strain and temperature changes.

[Features of lung dysfunction in children with Mycoplasma pneumoniae pneumonia with different chest imaging findings].

OBJECTIVE: To explore the features of pulmonary dysfunction in children with Mycoplasma pneumoniae pneumonia (MPP) with different chest imaging findings. METHODS: The clinical data from 215 children with MPP were reviewed. These patients were grouped based on chest image findings (bronchopneumonia, n=125; lobar pneumonia, n=69; interstitial pneumonia, n=21). Lung function parameters including forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF), and the maximum mid-expiratory flow rate (MMEF 25%-75%) were compared between the groups. RESULTS: In the acute stage, patients with bronchopneumonia had significantly lower PEF values (measured value and measured value/predicted value) than the other two groups of patients, children with lobar pneumonia had a significant lower MMEF 25%-75% than other patients, and children with interstitial pneumonia had a significantly lower FVC. All patients experienced an improvement in lung function parameters except FEV1 of the lobar pneumonia group in the recovery stage. CONCLUSIONS: Various features of pulmonary dysfunction can be observed among children with MPP with different chest imaging findings. Patients with bronchopneumonia mainly exhibit large airway dysfunction. The ones with lobar pneumonia mainly suffer small airway dysfunction, and those with interstitial pneumonia demonstrate both airway obstruction and restrictive ventilatory dysfunction.

Astaxanthin Alleviates Autoimmune Hepatitis by Modulating CD8+ T Cells: Insights From Mass Cytometry and Single-Cell RNA Sequencing Analyses.

Astaxanthin (ASX) is an oxygen-containing non-vitamin A carotenoid pigment. However, the role of ASX in autoimmune hepatitis (AIH) remains unclear. In this study, a mouse model of AIH is established induced by concanavalin A (ConA). Mass cytometry and single-cell RNA sequencing (scRNA-seq) are used to analyze the potential role of ASX in regulating the immune microenvironment of AIH. ASX treatment effectively alleviated liver damage induced by ConA and downregulated pro-inflammatory cytokines production in mice. Mass cytometry and scRNA-seq analyses revealed a significant increase in the number of CD8+ T cells following ASX treatment. Functional markers of CD8+ T cells, such as CD69, MHC II, and PD-1, are significantly downregulated. Additionally, specific CD8+ T cell subclusters (subclusters 4, 13, 24, and 27) are identified, each displaying distinct changes in marker gene expression after ASX treatment. This finding suggests a modulation of CD8+ T cell function by ASX. Finally, the key transcription factors for four subclusters of CD8+ T cells are predicted and constructed a cell-to-cell communication network based on receptor-ligand interactions probability. In conclusion, ASX holds the potential to ameliorate liver damage by regulating the number and function of CD8+ T cells.

Pectolinarigenin attenuates hepatic ischemia/reperfusion injury via activation of the PI3K/AKT/Nrf2 signaling pathway.

Hepatic ischemia/reperfusion (I/R) injury is an unavoidable complication of liver hepatectomy, transplantation, and systemic shock. Pectolinarigenin (Pec) is a flavonoid with many biological activities, which include anti-inflammatory, anti-apoptotic, and antioxidant stress. This study explored whether Pec pretreatment could reduce hepatic I/R injury and the potential mechanisms at play. After pretreatment of mice and AML12 cells with Pec, I/R and hypoxia/reoxygenation (H/R) models were established. By examining markers related to liver injury, cell viability, oxidative stress, inflammatory response, and apoptosis, the effect of Pec on important processes involved in hepatic I/R injury was assessed. Protein levels associated with the PI3K/AKT/Nrf2 pathway were analyzed by relative quantification to investigate possible pathways through which Pec plays a role in the I/R process. Pec treatment corrected abnormal transaminase levels resulting from I/R injury, improved liver injury, and increased AML12 cell viability. Moreover, Pec treatment inhibited oxidative stress, inflammation and apoptosis and could activate the PI3K/AKT/Nrf2 pathway during I/R and H/R. Further studies found that LY294002 (PI3K inhibitor) suppressed the protective effect of Pec on hepatic I/R injury. In summary, our results show that Pec inhibits oxidative stress, inflammatory responses, and apoptosis, thereby attenuating I/R-induced liver injury and H/R-induced cell damage via activation of the PI3K/AKT/Nrf2 pathway.

Status of asthma control in children and the effect of parents' knowledge, attitude, and practice (KAP) in China: a multicenter study.

BACKGROUND: Asthma is the most common chronic respiratory disease seriously endangering the health of children. But disease awareness and self-management skills are relatively poor in children; parents play an important role in the control of childhood asthma. OBJECTIVE: To investigate the status of asthma control and severity of asthma in children and to identify impact factors. METHODS: We studied 1 tertiary hospital in each of the 29 provinces. A total of 2,960 parents with children with asthma who visited those hospitals were selected for the knowledge, attitude, and practice (KAP) questionnaire survey, and separated into the controlled asthma group and uncontrolled asthma group according to children's asthma conditions in the past 12 months. Multivariate analysis was carried out based on the answers to 28 tested factors. RESULTS: In the past 12 months, 66.0% of children with asthma had asthma attacks, 26.8% visited an emergency room, and 16.2% were hospitalized. The total cost for asthma was significantly higher in the uncontrolled group than controlled group (χ(2) = 23.14, P < .01). Twelve protective factors of asthma control were founded, such as older age of children, long disease course, high KAP scores of parents, compliance with using nasal steroids, and knowledge of "3 or more times recurrent wheezing suggesting asthma." The risk factors were eczema and family history of asthma. CONCLUSION: Children's asthma is poorly controlled. The cost of asthma is significantly higher in uncontrolled asthma than in controlled. The age of children, course of asthma, personal history of allergy, family history of asthma, parents' education level, and parents' KAP are factors that affect asthma control.

Two single nucleotide polymorphisms in TSLP gene are associated with asthma susceptibility in Chinese Han population.

BACKGROUND: Asthma is a chronic inflammatory disease of the airway that is mediated by T-helper 2(TH2) cells. Thymic stromal lymphopoietin (TSLP) can aggravate asthmatic lung inflammation by activating dendritic cells (DCs) to promote TH2 differentiation. TSLP promoter polymorphisms are associated with susceptibility to bronchial asthma in Japanese population. We sought to determine whether single nucleotide polymorphisms (SNPs) in TSLP gene are associated with asthma in Chinese Han population. OBJECTIVE: To analyze the polymorphism of the two SNPs Rs2289276 and Rs2289278 in TSLP gene and to evaluate the association between the two SNPs and asthma susceptibility in Chinese Han population by using case-control study. METHODS: five hundred and thirty one asthmatic patients and 540 age-sex matched normal controls were collected and DNA were extracted from peripheral blood, then the genotypes of SNPs Rs2289276 and Rs2289278 in TSLP gene were detected with polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP), genotype and allele frequencies were calculated and analyzed with Chi-square test. RESULTS: Frequencies of CC/CT/TT genotypes at Rs2289276 site were 0.4706/0.4392/0.0902 in the asthmatic patients and 0.5604/0.3800/0.0595 in the healthy controls. Frequencies of CC/CG/GG genotypes at Rs2289278 site were 0.6502/0.2966/0.0532 in the asthmatic patients and 0.5795/0.3428/0.0777 in the healthy controls. The genotype and allele frequencies of the two SNPs in asthma patients were significantly different from those in the healthy controls. Rs2289278 C allele was correlated with decreased FEV(1): FVC (P ≤ .05). CONCLUSIONS: TSLP variants are significantly associated with bronchial asthma. TSLP might be a new therapeutic target molecule for asthma.

[Th1/Th2 immune response in bronchoalveolar lavage fluid in children with severe Mycoplasma pneumoniae pneumonia].

OBJECTIVE: To study the status of Th1/Th2 immune response and the value of the detection of cytokines in bronchoalveolar lavage fluids (BALF) by examining the levels of IFN-γ and IL-4 in BALF and serum in children with severe Mycoplasma pneumonia (MPP). METHODS: The levels of IFN-γ and IL-4 in BALF and serum were measured using ELISA in 25 children with severe MPP, 25 children with mild MPP and 25 children with foreign body in bronchus. RESULTS: The levels of IL-4 and IFN-γ and the IL-4/IFN-γ ratio in BALF in children with severe MPP were significantly higher than those in children with foreign body in bronchus (P<0.01 or P<0.05). The serum levels of IL-4 and the IL-4/IFN-γ ratio in children with severe MPP were significantly higher than those in children with foreign body in bronchus (P<0.01) or with mild MPP (P<0.05). The levels of IL-4 and the IL-4/IFN-γ ratio in BALF were significantly higher than in serum (P<0.05). CONCLUSIONS: The data suggest that the imbalance of Th1/Th2 exists in children with severe MPP and it seems to represent a predominant Th2-like cytokine response. The detection of cytokines in BALF appears to be more sensitive than in serum and may be of value in the diagnosis and therapy of MPP.

Recent Advances in Costimulatory Blockade to Induce Immune Tolerance in Liver Transplantation.

Liver transplantation is an effective therapy for end-stage liver disease. However, most postoperative patients must take immunosuppressive drugs to prevent organ rejection. Interestingly, some transplant recipients have normal liver function and do not experience organ rejection after the withdrawal of immunosuppressive agents. This phenomenon, called immune tolerance, is the ultimate goal in clinical transplantation. Costimulatory molecules play important roles in T cell-mediated immune responses and the maintenance of T cell tolerance. Blocking costimulatory pathways can alter T cell responses and prolong graft survival. Better understanding of the roles of costimulatory molecules has facilitated the use of costimulatory blockade to effectively induce immune tolerance in animal transplantation models. In this article, we review the state of the art in costimulatory pathway blockade for the induction of immune tolerance in transplantation and its potential application prospects for liver transplantation.

Association between Body Mass Index Status and Childhood Asthma Control.

Background: The association between body mass index (BMI) status and childhood asthma control is not well understood. The aim of this study was to explore the association between BMI status and childhood asthma control. Methods: Two hundred forty-two children, aged 6-11 years, with asthma were included. The outcome variables were asthma control levels assessed by the Chinese version of the childhood asthma control test (C-ACT), asthma-related hospitalizations or emergency department (ED) visits in the past 12 months, and forced expiratory volume in 1 second (FEV1) as a percentage of the predicted value. The associations between BMI status (underweight, overweight, or obese, relative to normal weight) and the three outcome variables were estimated by ordinal logistic regression, binary logistic regression, and multiple linear regression analyses. Results: No significant association was found between BMI status and asthma control levels assessed by C-ACT, and between BMI status and asthma-related hospitalizations or ED visits in the past 12 months, after adjustment for age, sex, father's education level, mother's education level, per capita family monthly income, medical insurance, passive smoking, allergic rhinitis, course of disease, and medication compliance. A significant association between underweight and FEV1 as a percentage of the predicted value was found after adjustment for the above covariates. However, no significant association between overweight or obese and FEV1 as a percentage of the predicted value was found. Conclusions: This study shows that BMI status may not be associated with childhood asthma control. Given the inconsistency in current evidence, more studies are needed in the future to investigate this association.

Atomically dispersed cobalt catalyst anchored on nitrogen-doped carbon nanosheets for lithium-oxygen batteries.

Developing single-site catalysts featuring maximum atom utilization efficiency is urgently desired to improve oxidation-reduction efficiency and cycling capability of lithium-oxygen batteries. Here, we report a green method to synthesize isolated cobalt atoms embedded ultrathin nitrogen-rich carbon as a dual-catalyst for lithium-oxygen batteries. The achieved electrode with maximized exposed atomic active sites is beneficial for tailoring formation/decomposition mechanisms of uniformly distributed nano-sized lithium peroxide during oxygen reduction/evolution reactions due to abundant cobalt-nitrogen coordinate catalytic sites, thus demonstrating greatly enhanced redox kinetics and efficiently ameliorated over-potentials. Critically, theoretical simulations disclose that rich cobalt-nitrogen moieties as the driving force centers can drastically enhance the intrinsic affinity of intermediate species and thus fundamentally tune the evolution mechanism of the size and distribution of final lithium peroxide. In the lithium-oxygen battery, the electrode affords remarkably decreased charge/discharge polarization (0.40 V) and long-term cyclability (260 cycles at 400 mA g-1).

Synthesis of MnO2-CuO-Fe2O3/CNTs catalysts: low-temperature SCR activity and formation mechanism.

MnO2-CuO-Fe2O3/CNTs catalysts, as a low-dimensional material, were fabricated by a mild redox strategy and used in denitration reactions. A formation mechanism of the catalysts was proposed. NO conversions of 4% MnO2-CuO-Fe2O3/CNTs catalyst of 43.1-87.9% at 80-180 °C were achieved, which was ascribed to the generation of amorphous MnO2, CuO and Fe2O3, and a high surface-oxygen (Os) content.