Seven-chain adaptive immune receptor repertoire analysis in rheumatoid arthritis reveals novel features associated with disease and clinically relevant phenotypes.

BACKGROUND: In rheumatoid arthritis (RA), the activation of T and B cell clones specific for self-antigens leads to the chronic inflammation of the synovium. Here, we perform an in-depth quantitative analysis of the seven chains that comprise the adaptive immune receptor repertoire (AIRR) in RA. RESULTS: In comparison to controls, we show that RA patients have multiple and strong differences in the B cell receptor repertoire including reduced diversity as well as altered isotype, chain, and segment frequencies. We demonstrate that therapeutic tumor necrosis factor inhibition partially restores this alteration but find a profound difference in the underlying biochemical reactivities between responders and non-responders. Combining the AIRR with HLA typing, we identify the specific T cell receptor repertoire associated with disease risk variants. Integrating these features, we further develop a molecular classifier that shows the utility of the AIRR as a diagnostic tool. CONCLUSIONS: Simultaneous sequencing of the seven chains of the human AIRR reveals novel features associated with the disease and clinically relevant phenotypes, including response to therapy. These findings show the unique potential of AIRR to address precision medicine in immune-related diseases.

Aging-Accelerated Mouse Prone 8 (SAMP8) Mice Experiment and Network Pharmacological Analysis of Aged Liupao Tea Aqueous Extract in Delaying the Decline Changes of the Body.

Aging and metabolic disorders feedback and promote each other and are closely related to the occurrence and development of cardiovascular disease, type 2 diabetes, neurodegeneration and other degenerative diseases. Liupao tea is a geographical indication product of Chinese dark tea, with a "red, concentrated, aged and mellow" flavor quality. In this study, the aqueous extract of aged Liupao tea (ALPT) administered by continuous gavage significantly inhibited the increase of visceral fat and damage to the intestinal-liver-microbial axis in high-fat modeling of SAMP8 (P8+HFD) mice. Its potential mechanism is that ALPT significantly inhibited the inflammation and aggregation formation pathway caused by P8+HFD, increased the abundance of short-chain fatty acid producing bacteria Alistipes, Alloprevotella and Bacteroides, and had a calorie restriction effect. The results of the whole target metabolome network pharmacological analysis showed that there were 139 potential active components in the ALPT aqueous extract, and the core targets of their actions were SRC, TP53, AKT1, MAPK3, VEGFA, EP300, EGFR, HSP90AA1, CASP3, etc. These target genes were mainly enriched in cancer, neurodegenerative diseases, glucose and lipid metabolism and other pathways of degenerative changes. Molecular docking further verified the reliability of network pharmacology. The above results indicate that Liupao tea can effectively delay the body's degenerative changes through various mechanisms and multi-target effects. This study revealed that dark tea such as Liupao tea has significant drinking value in a modern and aging society.

Hydrogen-bond-driven self-assembly of chemiluminophore affording long-lasting in vivo imaging.

Developing chemiluminescence probe with a slow kinetic profile, even a constant emission within analytical time, would improve the analytical sensitivity, but still remains challenging. This work reports a novel strategy to afford long-lasting in vivo imaging by developing a self-assembled chemiluminophore HPQCL-Cl via the introduction of the hydrogen-bond-driven self-assembled dye HPQ to Schaap's dioxetane. Compared with classical chemiluminophore HCL, self-assembled HPQCL-Cl was isolated from the physiological environment, thereby lowering its deprotonation and prolonging its half-life. Based on HPQCL-Cl, the long-lasting in vivo imaging of 9L-lacz tumor was achieved by developing a ß-gal-responsive probe. Its signals remained constant (<5% change) for about 20 min, which may provide a wide time window for the determination of ß-gal. This probe also showed high tumor-to-normal tissue ratio throughout tumor resection, highlighting its potential in image-guided clinical surgery.

Higher maternal thyroid resistance indices were associated with increased neonatal thyroid-stimulating hormone- analyses based on the Huizhou mother-infant cohort.

Objectives: This study aimed to explore the relationship of maternal thyroid function and thyroid resistance parameters with neonatal thyroid-stimulating hormone (TSH). Methods: This work was a longitudinal study. Singleton pregnant women without a history of thyroid disorders were recruited in their first prenatal visit from October 2018 to June 2020. Maternal thyroid markers including TSH, free triiodothyronine (FT3), free thyroxine (FT4), and neonatal TSH were tested in the clinical laboratory of the hospital by electrochemiluminescence immunoassay. Thyroid resistance indices including Thyroid Feedback Quantile-based Index (TFQI), TSH index (TSHI), and thyrotroph T4 resistance index (TT4RI) were estimated in accordance with maternal FT4 and TSH levels. Multivariable linear and logistic regression was applied to explore the associations of maternal thyroid indices with infantile TSH level. Results: A total of 3,210 mothers and 2,991 newborns with valid TSH data were included for analysis. Multivariable linear regression indicated that maternal thyroid variables were significantly and positively associated with neonatal TSH levels with standardized coefficients of 0.085 for TSH, 0.102 for FT3, 0.100 for FT4, 0.076 for TSHI, 0.087 for TFQI, and 0.089 for TT4RI (all P < 0.001). Compared with the lowest quartile, the highest quartile of TSHI [odds ratio (OR) = 1.590, 95% CI: 0.928-2.724; Ptrend = 0.025], TFQI (OR = 1.746, 95% CI: 1.005-3.034; Ptrend = 0.016), and TT4RI (OR = 1.730, 95% CI: 1.021-2.934; Ptrend = 0.030) were significantly associated with an increased risk of elevated neonatal TSH (>5 mIU/L) in a dose-response manner. Conclusion: The longitudinal data demonstrated that maternal thyroid resistance indices and thyroid hormones in the first half of gestation were positively associated with neonatal TSH levels. The findings offered an additionally practical recommendation to improve the current screening algorithms for congenital hypothyroidism.

Intrapleural interleukin-2-expressing oncolytic virotherapy enhances acute antitumor effects and T-cell receptor diversity in malignant pleural disease.

OBJECTIVE: The mainstay of treatment for patients with malignant pleural disease is fluid drainage and systemic therapy. A tumor-specific oncolytic virus or T-cell-activating interleukin-2 immunotherapy may provide an opportunity for local control. We previously developed a vaccinia virus-expressing interleukin-2, an oncolytic virus that mediated tumor regression in preclinical peritoneal tumor models with expansion of tumor-infiltrating lymphocytes. We evaluated the antitumor efficacy and immune modulatory effects of vaccinia virus-expressing interleukin-2 in malignant pleural disease. METHODS: A murine model of malignant pleural disease was established with percutaneous intrapleural deposition of the Lewis lung carcinoma cell line and monitored with bioluminescent imaging. After intrapleural or systemic administration of vaccinia viruses (vaccinia virus yellow fluorescent protein control, vaccinia virus-expressing interleukin-2), systemic anti-programmed cell death-1 antibody, or combination therapy (vaccinia virus-expressing interleukin-2 and anti-programmed cell death-1), tumor mass, immune cell infiltration, T-cell receptor diversity, and survival were assessed. RESULTS: Intrapleural vaccinia virus resulted in significant tumor regression compared with phosphate-buffered saline control (P < .05). Inclusion of the interleukin-2 transgene further increased intratumoral CD8+ T cells (P < .01) and programmed cell death-1 expression on CD8+ tumor-infiltrating lymphocytes (P < .001). Intrapleural vaccinia virus-expressing interleukin-2 was superior to systemic vaccinia virus-expressing interleukin-2, with reduced tumor burden (P < .0001) and improved survival (P < .05). Intrapleural vaccinia virus-expressing interleukin-2 alone or combined treatment with systemic anti-programmed cell death-1 reduced tumor burden (P < .01), improved survival (P < .01), and increased intratumoral αß T-cell receptor diversity (P < .05) compared with systemic anti-programmed cell death-1 monotherapy. CONCLUSIONS: Intrapleural vaccinia virus-expressing interleukin-2 reduced tumor burden and enhanced survival in a murine malignant pleural disease model. Increased CD8+ tumor-infiltrating lymphocytes and αß T-cell receptor diversity are associated with enhanced response. Clinical trials will enable assessment of intrapleural vaccinia virus-expressing interleukin-2 therapy in patients with malignant pleural disease.

UV illumination-enhanced ultrasensitive ammonia gas sensor based on (001)TiO2/MXene heterostructure for food spoilage detection.

Ammonia has been used as an important marker to indicate the extent of food spoilage. However, current gas sensors for ammonia suffer from either insufficient sensitivity and selectivity or unsatisfactory levels of automation, impeding their practical application for on-site and real-time monitoring of food quality. To overcome these limitations, we propose here the design of a sensing material by in-situ growing (001)TiO2 onto a two-dimensional transition-metal carbide (Ti3C2Tx, MXene). In this design, TiO2 with a highly active (001) crystal plane provides efficient photogeneration under UV irradiation, while Ti3C2Tx can store holes through Schottky junction formed at the interface with TiO2, which greatly promotes the separation of electron-hole pairs, thereby enhancing ammonia sensing performance. By further introducing UV light for electron excitation, the (001)TiO2/Ti3C2Tx based sensor shows 34 times higher sensitivity for ammonia (30 ppm) than that of Ti3C2Tx. The density functional theory further revealed that the (001) plane of TiO2 and Ti3C2Tx composite configuration exhibited the highest adsorption affinity towards ammonia. Finally, an integrated circuit alarm system including near-field communication and a micro-controller system was designed to detect the decay process of fresh pork, fish, and shrimp. We believe such a sensing technology holds great promise in food quality monitoring.

Room-Temperature Benzene Sensing with Au-Doped ZnO Nanorods/Exfoliated WSe2 Nanosheets and Density Functional Theory Simulations.

A gold-doped zinc oxide (Au-ZnO)/exfoliated tungsten diselenide (exfoliated WSe2) nanocomposite-based gas sensor toward benzene with high sensing properties was demonstrated. Epoxy resin was used as the matrix of the Au-ZnO/exfoliated WSe2 nanocomposite sensor. The straw-shaped Au-ZnO was synthesized by the hydrothermal method, and WSe2 nanosheets (NSs) were prepared via hydrothermal and liquid-phase exfoliation methods. The properties of Au-ZnO/exfoliated WSe2 nanoheterostructures constructed by self-assembly technology have been confirmed via a series of characterization methods. The benzene-sensing performances of sensors were tested at 25 °C. Compared with Au-ZnO, WSe2, and their composites, the Au-ZnO/exfoliated WSe2 sensor has a significant performance improvement, including a higher response and linear fit degree, better selectivity and repeatability, and faster detection rate. The significantly enhanced sensing properties of the Au-ZnO/exfoliated WSe2 sensor can be ascribed to the doping of Au nanoparticles, the increase in the specific surface area and adsorption sites of NSs after exfoliation, and the cooperative interface combination of the ZnO/WSe2 heterojunction. Furthermore, the sensitivity mechanism of the composite sensor to benzene was explored by density functional theory simulations.

Systemic Immune-Inflammation Index Predicts 3-Month Functional Outcome in Acute Ischemic Stroke Patients Treated with Intravenous Thrombolysis.

BACKGROUND AND PURPOSE: Systemic immune-inflammation index (SII), a novel inflammation index derived from counts of circulating platelets, neutrophils and lymphocytes, has been studied in developing incident cancer. However, the clinical value of SII in acute ischemic stroke (AIS) patients had not been further investigated. Therefore, we aimed to explore the association between SII and severity of stroke as well as 3-month outcome of AIS patients. METHODS: A total of 216 AIS patients receiving intravenous thrombolysis (IVT) and 875 healthy controls (HCs) were retrospectively recruited. Blood samples were collected within 24h after admission. Severity of stroke was assessed by the National Institute of Health stroke scale (NIHSS) scores on admission and poor 3-month functional outcome was defined as Modified Rankin Scale (mRS) > 2. RESULTS: SII levels in AIS patients were higher than in HCs. The cut-off value of SII is 545.14×109/L. Patients with SII > 545.14×109/L had higher NIHSS scores (median: 5 vs 9, p < 0.001), a positive correlation between SII and NIHSS was observed (rs = 0.305, p < 0.001). Multivariate logistic regression analyses showed that high SII was one of the independent risk factors for poor prognosis at 3 months of AIS patients (OR = 3.953, 95% CI = 1.702-9.179, p = 0.001). The addition of SII to the conventional prognostic model improved the reclassification (but not discrimination) of the functional outcome (net reclassification index 39.3%, p = 0.007). CONCLUSION: SII is correlated with stroke severity at admission and can be a novel prognostic biomarker for AIS patients treated with IVT.

Research progress on the potential delaying skin aging effect and mechanism of tea for oral and external use.

Skin aging is characterized by the gradual loss of elasticity, the formation of wrinkles and various color spots, the degradation of extracellular matrix proteins, and the structural changes of the dermis. With the increasingly prominent problems of environmental pollution, social pressure, ozone layer thinning and food safety, skin problems have become more and more complex. The skin can reflect the overall health of the body. Skincare products for external use alone cannot fundamentally solve skin problems; it needs to improve the overall health of the body. Based on the literature review in recent 20 years, this paper systematically reviewed the potential delaying effect of tea and its active ingredients on skin aging by oral and external use. Tea is the second-largest health drink after water. It is rich in tea polyphenols, l-theanine, tea pigments, caffeine, tea saponins, tea polysaccharides and other secondary metabolites. Tea and its active substances have whitening, nourishing, anti-wrinkle, removing spots and other skincare effects. Its mechanism of action is ultraviolet absorption, antioxidant, anti-inflammatory, inhibition of extracellular matrix aging, inhibiting the accumulation of melanin and toxic oxidation products, balancing intestinal and skin microorganisms, and improving mood and sleep, among other effects. At present, tea elements skincare products are deeply loved by consumers. This paper provides a scientific theoretical basis for tea-assisted beauty and the high-end application of tea in skincare products.

A human monoclonal antibody blocks malaria transmission and defines a highly conserved neutralizing epitope on gametes.

Malaria elimination requires tools that interrupt parasite transmission. Here, we characterize B cell receptor responses among Malian adults vaccinated against the first domain of the cysteine-rich 230 kDa gamete surface protein Pfs230, a key protein in sexual stage development of P. falciparum parasites. Among nine Pfs230 human monoclonal antibodies (mAbs) that we generated, one potently blocks transmission to mosquitoes in a complement-dependent manner and reacts to the gamete surface; the other eight show only low or no blocking activity. The structure of the transmission-blocking mAb in complex with vaccine antigen reveals a large discontinuous conformational epitope, specific to domain 1 of Pfs230 and comprising six structural elements in the protein. The epitope is conserved, suggesting the transmission-blocking mAb is broadly functional. This study provides a rational basis to improve malaria vaccines and develop therapeutic antibodies for malaria elimination.

Long noncoding RNA WDFY3-AS2 suppresses tumor progression by acting as a competing endogenous RNA of microRNA-18a in ovarian cancer.

Ovarian cancer (OC) is a fatal cancer in women, mainly due to its aggressive nature and poor survival rate. The lncRNA-miRNA-mRNA (long noncoding RNA-microRNA-messenger RNA) interaction is promising biomarkers for the improving prognosis of OC. Therefore, we explored the regulatory mechanism of WDFY3-AS2/miR-18a/RORA axis involved in the biological activities of OC cells. Microarray analysis predicted differentially expressed lncRNA, miRNA, and mRNA related to OC, followed by investigating the relationship among them. The expression patterns of the identified lncRNA WDFY3-AS2, miR-18a, and RORA were measured in OC tissue and cells. Gain- and loss-of-function experiments were performed to characterize the effect of lncRNA WDFY3-AS2 on OC cells, as well as the involvement of miR-18a and RAR related orphan receptor A (RORA). The in vitro assays were validated by in vivo experiments. According to bioinformatics analysis, WDFY3-AS2 was speculated to affect OC by sponging miR-18a and modulating RORA. WDFY3-AS2 and RORA were underexpressed in OC, while miR-18a was highly expressed. Notably, WDFY3-AS2 acts as a competing endogenous RNA to sponge miR-18a and upregulate RORA. Upon overexpressing WDFY3-AS2 or inhibiting miR-18a, RORA expression was increased, thereby the OC cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition (EMT) were suppressed, accompanied by enhanced apoptosis. In vivo experiments confirmed that the tumor growth was reduced in response to overexpressed WDFY3-AS2 or inhibited miR-18a. Taken together, the lncRNA WDFY3-AS2/miR-18a axis regulates the tumor progression of OC by targeting RORA, providing new insights for prevention and control of OC.

LncRNA-CTS promotes metastasis and epithelial-to-mesenchymal transition through regulating miR-505/ZEB2 axis in cervical cancer.

Cervical carcinoma (CC) is the second most common cancer in females. In order to improve current anti-metastasis strategies for CC, it is important to improve our understanding of the mechanisms involved in epithelial-to-mesenchymal transition (EMT). This study aimed to elucidate the potential role of a novel long non-coding RNA (lncRNA)-CTS and the mechanisms underlying EMT in CC. The expression levels of lncRNA-CTS and miR-505 were detected using quantitative reverse transcriptase polymerase chain reaction in CC specimens and cells (HeLa, SiHa, Ca-Ski, C-33A, and HT-3). Further experiments including wound scratch and transwell invasion assays, Western blotting, immunofluorescence, and luciferase assays were used to investigate the function of lncRNA-CTS/miR-505/ZEB2 in vitro. In addition, a tumor xenograft model was used to assess the effect of lncRNA-CTS in vivo. The expression levels of lncRNA-CTS and miR-505 were correlated with the metastasis-associated clinicopathological features of CC patients. Moreover, lncRNA-CTS was associated with a poor prognosis in CC patients. In vitro and in vivo experiments, along with gain- and loss-of-function studies, showed that lncRNA-CTS enhanced cell migration, invasion, and the transforming growth factor (TGF)-ß1-induced-EMT process. Data also showed that lncRNA-CTS could function as a competing endogenous RNA for miR-505 in CC cells. Further investigations disclosed that ZEB2 was demonstrated as a downstream target of miR-505, and subsequently exerted its metastatic effects via the lncRNA-CTS/miR-505/ZEB2 axis in CC cells. Finally, lncRNA-CTS activated the SMAD/TGF pathway via miR-505 in CC cells. Collectively, our results demonstrate the importance of the lncRNA-CTS/miR-505/ZEB2 axis in CC. LncRNA-CTS can predispose CC patients to metastases and may represent a promising therapeutic target for CC.

High throughput sequencing of T-cell receptor repertoire using dry blood spots.

BACKGROUND: Immunology research, particularly next generation sequencing (NGS) of the immune T-cell receptor ß (TCRß) repertoire, has advanced progression in several fields, including treatment of various cancers and autoimmune diseases. This study aimed to identify the TCR repertoires from dry blood spots (DBS), a method that will help collecting real-world data for biomarker applications. METHODS: Finger-prick blood was collected onto a Whatman filter card. RNA was extracted from DBS of the filter card, and fully automated multiplex PCR was performed to generate a TCRß chain library for next generation sequencing (NGS) analysis of unique CDR3s (uCDR3). RESULTS: We demonstrated that the dominant clonotypes from the DBS results recapitulated those found in whole blood. According to the statistical analysis and laboratory confirmation, 40 of 2-mm punch disks from the filter cards were enough to detect the shared top clones and have strong correlation in the uCDR3 discovery with whole blood. uCDR3 discovery was neither affected by storage temperatures (room temperature versus - 20 °C) nor storage durations (1, 14, and 28 days) when compared to whole blood. About 74-90% of top 50 uCDR3 clones of whole blood could also be detected from DBS. A low rate of clonotype sharing, 0.03-1.5%, was found among different individuals. CONCLUSIONS: The DBS-based TCR repertoire profiling method is minimally invasive, provides convenient sampling, and incorporates fully automated library preparation. The system is sensitive to low RNA input, and the results are highly correlated with whole blood uCDR3 discovery allowing study scale-up to better understand the relationship and mutual influences between the immune and diseases.

Belimumab promotes negative selection of activated autoreactive B cells in systemic lupus erythematosus patients.

Belimumab has therapeutic benefit in active systemic lupus erythematosus (SLE), especially in patients with high-titer anti-dsDNA antibodies. We asked whether the profound B cell loss in belimumab-treated SLE patients is accompanied by shifts in the immunoglobulin repertoire. We enrolled 15 patients who had been continuously treated with belimumab for more than 7 years, 17 matched controls, and 5 patients who were studied before and after drug initiation. VH genes of sort-purified mature B cells and plasmablasts were subjected to next-generation sequencing. We found that B cell-activating factor (BAFF) regulates the transitional B cell checkpoint, with conservation of transitional 1 (T1) cells and approximately 90% loss of T3 and naive B cells after chronic belimumab treatment. Class-switched memory B cells, B1 B cells, and plasmablasts were also substantially depleted. Next-generation sequencing revealed no redistribution of VH, DH, or JH family usage and no effect of belimumab on representation of the autoreactive VH4-34 gene or CDR3 composition in unmutated IgM sequences, suggesting a minimal effect on selection of the naive B cell repertoire. Interestingly, a significantly greater loss of VH4-34 was observed among mutated IgM and plasmablast sequences in chronic belimumab-treated subjects than in controls, suggesting that belimumab promotes negative selection of activated autoreactive B cells.

Effect of nitrite exposure on the antioxidant enzymes and glutathione system in the liver of bighead carp, Aristichthys nobilis.

Nitrite (NO2-) can cause oxidative stress in aquatic animal when it accumulates in the organism, resulting in different toxic effects on fish. In the present study, we investigated the effects of nitrite exposure on the antioxidant enzymes and glutathione system in the liver of Bighead carp (Aristichthys nobilis). Fish [Initial average weight: (180.05 ±â€¯0.092) g] were exposed to 48.634 mg/L nitrite for 96 h, and a subsequent 96 h for the recovery test. Fish livers were collected to assay antioxidant enzymes activity, hepatic structure and expression of genes after 0 h, 6 h, 12 h, 24 h, 48 h, 72 h, 96 h of exposure and12 h, 24 h, 48 h, 72 h, 96 h of recovery. The results showed that the activity of glutathione peroxidase (GSH-Px), glutathione S-transferase (GST), and glutathione reductase (GR) increased significantly in the early stages of nitrite exposure. The study also showed that nitrite significantly up-regulated the mRNA levels of glutathione peroxidase (GSH-Px), glutathione S-transferase (GST), and glutathione reductase (GR) after 6, 48, and 72 h of exposure respectively. Nitrite also increased the formation of malondialdehyde (MDA), oxidized glutathione (GSSG), and the activity of catalase (CAT). Nitrite was observed to reduce the activity of superoxide dismutase (SOD) and the level of glutathione (GSH). In the recovery test, GSH and the GSSG recovered but did not return to pre-stress levels. The results suggested that the glutathione system played important roles in nitrite-induced oxidative stress in fish. The bighead carp responds to oxidative stress by enhancing the activity of GSH-Px, GST, GR and up-regulating the expression level of GSH-Px, GST, GR, a whilst simultaneously maintaining the dynamic balance of GSH/GSSG. CAT was also indispensable. They could reduce the degree of lipid peroxidation, and ultimately protect the body from oxidative damage.

Nickel-catalyzed cross-coupling of ß-carbonyl alkenyl pivalates with arylzinc chlorides.

The nickel-catalyzed cross-coupling reaction of ß-carbonyl alkenyl pivalates with arylzinc reagents generates 3-aryl-substituted α,ß-unsaturated carbonyl compounds via C-O bond cleavage. The reaction features mild reaction conditions, a wide scope of substrates, and good functional group tolerance.

Regulation mechanism of oxidative stress induced by high glucose through PI3K/Akt/Nrf2 pathway in juvenile blunt snout bream (Megalobrama amblycephala).

This study was conducted to investigate the effects of oral administration of a high concentration of glucose on the respiratory burst, antioxidant status, and hepatic gene expression of heme oxygenase-1 (ho1) and PI3K/Akt/Nrf2-related signaling molecules in juvenile blunt snout bream (Megalobrama amblycephala). Blunt snout bream juveniles with an initial body weight of 19.94 ± 0.58 g were orally fed with a high concentration of glucose (3 g/kg body weight). The results indicated that plasma glucose exhibited a biphasic response. Acute and persistent hyperglycemia due to the oral glucose administration significantly reduced (P < 0.05) the white blood cell count, red blood cell count, and hemoglobin content and caused oxidative stress (significantly increased alanine aminotransferase, aspartate transaminase, alkaline phosphatase, and glucose levels) and early apoptosis of hepatocytes in the fish. Hepatic superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activities increased rapidly (P < 0.05) as protection from oxidative stress and were downregulated (P < 0.05) because of persistent hyperglycemia. Blood respiratory burst was significantly reduced (P < 0.05) because of hyperglycemia and showed a trend that was opposite to that of plasma glucose. Slight upregulation of nrf2 mRNA and antioxidants acts as a compensative protection mechanism, and the downregulated PI3K/Akt pathway blocked this function of Nrf2. In conclusion, the PI3K/Akt pathway and Nrf2 mediated the antioxidative mechanism independently in the blunt snout bream juveniles subjected to the oral administration of a high glucose concentration.

Stigma of HIV Testing on Online HIV Forums: Self-Stigma and the Unspoken.

Most studies examining HIV-related content in web forums have revolved around the most frequently used terms in HIV-related messages and topics, as well as the supportive nature of those messages. The current study explored barriers that prevent individuals from seeking HIV testing (specifically stigma). The current study analyzed a total of 210 threads and 319 posts, yielding 13 threads that revealed how individuals self-stigmatize and expressed how the fear of being diagnosed prevented them from seeking HIV testing. Results suggest that forums or online communities may perpetuate subculture values that deviate from mainstream values. Another important finding is that there is a lack of HIV testing information in forums for adolescents, which may contribute to the trend of young individuals engaging in risky sexual behaviors not getting tested in a timely fashion. [Journal of Psychosocial Nursing and Mental Health Services, 55(12), 34-43.].

Dietary arginine affects the insulin signaling pathway, glucose metabolism and lipogenesis in juvenile blunt snout bream Megalobrama amblycephala.

This study evaluated the mechanisms governing insulin resistance, glucose metabolism and lipogenesis in juvenile fish fed with graded levels of dietary arginine. The results showed that, compared with the control group (0.87%), 2.31% dietary arginine level resulted in the upregulation of the relative gene expression of IRS-1, PI3K and Akt in the insulin signaling pathway, while 2.70% dietary arginine level led to inhibition of these genes. 1.62% dietary arginine level upregulated glycolysis by increasing GK mRNA level; 2.70% dietary arginine level upregulated gluconeogenesis and resulted in high plasma glucose content by increasing PEPCK and G6P mRNA level. Furthermore, 2.70% dietary arginine level significantly lowered GLUT2 and increased PK mRNA levels. 1.62% dietary arginine level significantly upregulated ACC, FAS and G6PDH mRNA levels in the fat synthesis pathway and resulted in high plasma TG content. These results indicate that 1.62% dietary arginine level improves glycolysis and fatty acid synthesis in juvenile blunt snout bream. However, 2.70% dietary arginine level results in high plasma glucose, which could lead to negative feedback of insulin resistance, including inhibition of IRS-1 mRNA levels and activation of gluconeogenesis-related gene expression. This mechanism seems to be different from mammals at the molecular level.