ABSTRACT
Lung squamous cell carcinoma (LUSC) is one of the most common malignant tumors of the respiratory. Pyroptosis plays an essential role in cancer, but there is limited research investigating pyroptosis in LUSC. In this study, pyroptosis-related genes were observed to have extensive multiomics alterations in LUSC through analysis of the TCGA database. Utilizing machine learning for selection and verifying expression levels, GSDMC was chosen as the critical gene for further experiments. Our research found that GSDMC is overexpressed in LUSC tissues and cells, and is associated with poor prognosis. Knockdown of GSDMC in LUSC inhibits cell proliferation, invasion, metastasis, chemotherapeutic sensitivity, and reduced tumor formation in nude mice, accompanied by downregulation of proliferative and EMT-related protein expression. However, these effects were counteracted in cells where GSDMC is overexpressed. Mechanistically, the oncogenic role of GSDMC is primarily achieved through the activation of the AKT/mTOR pathway, and this effect can be significantly reversed by rapamycin. Finally, SMAD4's interaction with the promoter region of GSDMC results in the suppression of GSDMC expression. In summary, our study through bioinformatics and experimental approaches not only proves that SMAD4 regulates the protumorigenic role of GSDMC through transcriptional targeting, but also indicates the possibility of developing the SMAD4/GSDMC/AKT/mTOR signaling axis as a potential biomarker and treatment target for LUSC.
ABSTRACT
OBJECTIVES: To explore the association between tea, coffee, and caffeine consumption and the risk of female infertility. METHODS: We analyzed data from 2099 females aged 18 to 44 years, participating in the National Health and Nutrition Examination Survey (NHANES) 2013-2018. We used generalized linear models (GLM) and generalized additive model (GAM) to investigate the dose-response relationship between the tea, coffee, and caffeine consumption and infertility, adjusting for potential confounders. RESULTS: A non-linear relationship was detected between tea consumption and infertility and the inflection point was 2 cups/day. On the right side of the inflection point, we did not detect a significant association. However, on the left side, we found a negative relationship between tea consumption and infertility (OR: 0.73; 95% CI: 0.57 to 0.93; P = 0.0122). Meanwhile, our study found no significant association between coffee (0.96, 0.81 to 1.13, P = 0.6189) or caffeine consumption (1.15, 0.93 to 1.42, P = 0.2148) and female infertility. CONCLUSIONS: Tea consumption was non-linearly associated with infertility, whereas no significant associations were found between coffee, caffeine consumption and infertility.
Subject(s)
Caffeine , Coffee , Infertility, Female , Tea , Humans , Female , Tea/adverse effects , Coffee/adverse effects , Caffeine/adverse effects , Caffeine/administration & dosage , Adult , Cross-Sectional Studies , Infertility, Female/epidemiology , Young Adult , Adolescent , Nutrition Surveys , Risk FactorsABSTRACT
OBJECTIVES: To explore the relationship between different types of physical activity and female infertility. METHODS: This study analyzed data from 2,796 female participants aged 18-44 years in the United States, obtained from the National Health and Nutrition Examination Survey (NHANES) database spanning the years 2013 to 2020. Multiple logistic regression analyses and generalized linear models were used to explore the relationship between different types of physical activity and infertility after adjusting for potential confounding factors. RESULTS: We found a non-linear relationship between recreational activities and infertility with an inflection point of 5.83 h/week (moderate intensity), while work activities and traffic-related activities did not. On the left side of the inflection point, there was no significant association between recreational activity time and infertility (OR = 0.93, 95% CI: 0.86 to 1.02, P = 0.1146), but on the right side of the inflection point, there was a positive association between recreational activity time and the risk of infertility (OR = 1.04, 95% CI: 1.02 to 1.06, P = 0.0008). CONCLUSIONS: The relationship between different types of physical activity and female infertility varies. We acknowledge the potential influence of confounding variables on this relationship. However, we have already adjusted for these potential variables in our analysis. Therefore, our findings suggest that appropriate recreational activity programs are essential for promoting reproductive health in women of reproductive age. Nevertheless, it is important to note that the observed association does not imply causality. Given the limitations of cross-sectional studies, further prospective cohort studies are needed to explore the causal relationship while accounting for additional confounding factors.
Subject(s)
Exercise , Infertility, Female , Nutrition Surveys , Humans , Female , Adult , Infertility, Female/epidemiology , Infertility, Female/etiology , Exercise/physiology , Young Adult , Adolescent , United States/epidemiology , Cross-Sectional StudiesABSTRACT
Negative pressure wound therapy (NPWT) is effective in repairing serious skin injury. The dressing used in the NPWT is important for wound healing. In this paper, we develop biodegradable amphiphilic polyurethanes (PUs) and fabricate the PUs into sponges as wound dressings (Bi@e) with Janus pore architectures for NPWT. The Bi@e is adaptive to all the stages of the wound healing process. The Janus Bi@e sponge consists of two layers: the dense hydrophobic upper layer with small pores provides protection and support during negative pressure drainage, and the loose hydrophilic lower layer with large pores absorbs large amounts of wound exudate and maintains a moist environment. Additionally, antibacterial agent silver sulfadiazine (SSD) is loaded into the sponge against Escherichia coli and Staphylococcus aureus with a concentration of 0.50 wt%. The Janus sponge exhibits a super absorbent capacity of 19.53 times its own water weight and remarkable resistance to compression. In a rat skin defect model, the Janus Bi@e sponge not only prevents the conglutination between regenerative skin and dressing but also accelerates wound healing compared to commercially available NPWT dressing. The Janus Bi@e sponge is a promising dressing for the NPWT.
Subject(s)
Negative-Pressure Wound Therapy , Animals , Rats , Wound Healing , Bandages , Skin , SuppurationABSTRACT
Fish nocardiosis is a chronic disease mainly caused by Nocardia seriolae, which occurs in a variety of economically cultured freshwater and marine fish. Studies have shown that DNA vaccine is an effective treatment to protect fish from bacterial infection. In our previous experiment, an in vivo-induced gene of N. seriolae, encoding phosphoketolase (PK) family protein, was identified by in vivo-induced antigen technology. In the present study, the antigenic gene encoding PK family protein was analyzed by bioinformatics and further inserted into the eukaryotic expression vector pcDNA3.1-myc-his-A for DNA vaccine development. The immunological effects of pcDNA-PK DNA vaccine were assessed in hybrid snakehead (Channa maculata â × Channa argus â), showing induction in several serum enzyme activity parameters (including LZM, SOD, ACP and AKP), increasing in specific-antibody IgM levels, as well as up-regulation in six immune-related genes (CD4, CD8α, TNFα, IL-1ß, MHCIα and MHCIIα). Moreover, an immune-protection with a relative survival rate was provided at 53.82 % following artificial challenge with N. seriolae in vaccinated fish in comparison to the control group. In summary, these results indicate that pcDNA-PK DNA vaccine could boost strong immune responses in hybrid snakehead and show preferably protective efficacy against N. seriolae, which may be applied in aquaculture to control fish nocardiosis.
Subject(s)
Bacterial Vaccines , Fish Diseases , Nocardia Infections , Nocardia , Vaccines, DNA , Animals , Nocardia/immunology , Nocardia Infections/veterinary , Nocardia Infections/immunology , Nocardia Infections/prevention & control , Fish Diseases/immunology , Fish Diseases/prevention & control , Vaccines, DNA/immunology , Bacterial Vaccines/immunology , Aldehyde-Lyases/genetics , Aldehyde-Lyases/immunology , Fishes/immunology , Bacterial Proteins/immunology , Bacterial Proteins/geneticsABSTRACT
Nocardia seriolae has been identified as the causative agent of fish nocardiosis, resulting in serious economic losses in aquaculture. With an aim to screen potential candidates for vaccine development against N. seriolae, the in vivo-induced genes of N. seriolae in hybrid snakehead (Channa maculate â × Channa argus â) model were profiled via in vivo-induced antigen technology (IVIAT) in the present study, and 6 in vivo-induced genes were identified as follows: IS701 family transposase (is701), membrane protein insertase YidC (yidC), ergothioneine biosynthesis glutamate-cysteine ligase (egtA), molybdopterin respectively-dependent oxidoreductase (mol), phosphoketolase family protein (Ppl), hypothetical protein 6747 (hp6747). Additionally, the yidC was inserted into eukaryotic expression vector pcDNA3.1-myc-his-A to construct a DNA vaccine named as pcDNA-YidC to evaluate immunoprotection in hybrid snakehead after artificial challenge with N. serioale. Results showed that the transcription of yidC was detected in spleen, trunk kidney, muscle and liver in vaccinated fish, suggesting that this antigenic gene can be recombinantly expressed in fish. Meanwhile, indexes of humoral immunity were evaluated in the vaccinated fish through assessing specific-antibody IgM and serum enzyme activities, including lysozyme (LZM), superoxide dismutase (SOD), acid phosphatase (ACP) and alkaline phosphatase (AKP). Quantitative real-time PCR analysis indicated that pcDNA-YidC DNA vaccine could notably enhance the expression of immune-related genes (CD4ãCD8αãMHCIIαãTNFαãIL-1ß and MHCIα) in 4 tissues (spleen, trunk kidney, muscle and liver) of the vaccinated fish. Finally, an immuno-protection with a relative survival rate of 65.71 % was displayed in vaccinated fish in comparison to the control groups. Taken together, these results indicate that pcDNA-YidC DNA vaccine could boost strong immune responses in hybrid snakehead and show preferably protective efficacy against N. seriolae, indicating that IVIAT is a helpful strategy to screen the highly immunogenic antigens for vaccine development against fish nocardiosis.
Subject(s)
Fish Diseases , Nocardia Infections , Nocardia , Vaccines, DNA , Animals , FishesABSTRACT
BACKGROUND: Fractures of hands and feet are common in children, but relevant epidemiological studies are currently lacking. We aim to study the epidemiological characteristics of hand and foot fractures and growth plate injuries in children and provide a theoretical basis for their prevention, diagnosis, and treatment. METHODS: We retrospectively analyzed the data of children with hand and foot fractures who were hospitalized at Shenzhen Children's Hospital between July 2015 and December 2020. Data on demographic characteristics, fracture site, treatment method, etiology of injury, and accompanying injuries were collected. The children were divided into four age groups: infants, preschool children, school children, and adolescents. The fracture sites were classified as first-level (the first-fifth finger/toe, metacarpal, metatarsal, carpal, and tarsal) and second-level (the first-fifth: proximal phalanx, middle phalanx, distal phalanx, metacarpal, and metatarsal) sites. The changing trends in fracture locations and injury causes among children in each age group were analyzed. RESULTS: Overall, 1301 children (1561 fractures; 835 boys and 466 girls) were included. The largest number of fractures occurred in preschool children (n = 549, 42.20%), with the distal phalanx of the third finger being the most common site (n = 73, 15.57%). The number of fractures in adolescents was the lowest (n = 158, 12.14%), and the most common fracture site was the proximal phalanx of the fifth finger (n = 45, 29.61%). Of the 1561 fractures, 1143 occurred in the hands and 418 in the feet. The most and least common first-level fracture sites among hand fractures were the fifth (n = 300, 26.25%) and first (n = 138, 12.07%) fingers, respectively. The most and least common first-level foot fracture locations were the first (n = 83, 19.86%) and fourth (n = 26, 6.22%) toes, respectively. The most common first-level and second level etiologies were life related injuries (n = 1128, 86.70%) and clipping injuries (n = 428, 32.90%), respectively. The incidence of sports injuries gradually increased with age, accounting for the highest proportion in adolescents (26.58%). Hand and foot fractures had many accompanying injuries, with the top three being nail bed injuries (570 cases, 36.52%), growth plate injuries (296 cases, 18.96%), and distal severed fracture (167 cases, 10.70%). Among the 296 growth plate injuries, 246 occurred on the hands and 50 on the feet. CONCLUSIONS: In contrast to previous epidemiological studies on pediatric hand and foot fractures, we mapped the locations of these fractures, including proximal, shaft, distal, and epiphyseal plate injuries. We analyzed the changing trends in fracture sites and injury etiologies with age. Hand and foot fractures have many accompanying injuries that require attention during diagnosis and treatment. Doctors should formulate accident protection measures for children of different ages, strengthen safety education, and reduce the occurrence of accidental injuries.
Subject(s)
Foot Injuries , Fractures, Bone , Hand Injuries , Metacarpal Bones , Salter-Harris Fractures , Male , Child, Preschool , Infant , Female , Adolescent , Child , Humans , Retrospective Studies , Salter-Harris Fractures/complications , Fractures, Bone/epidemiology , Fractures, Bone/etiology , Fractures, Bone/diagnosis , Hand Injuries/epidemiology , Hand Injuries/etiology , Hand Injuries/therapy , Metacarpal Bones/injuries , Foot Injuries/epidemiology , Foot Injuries/etiology , Foot Injuries/therapyABSTRACT
Dopant-free hole transporting materials (HTMs) is significant to the stability of perovskite solar cells (PSCs). Here, we developed a novel star-shape arylamine HTM, termed Py-DB, with a pyrene core and carbon-carbon double bonds as the bridge units. Compared to the reference HTM (termed Py-C), the extension of the planar conjugation backbone endows Py-DB with typical intermolecular π-π stacking interactions and excellent solubility, resulting in improved hole mobility and film morphology. In addition, the lower HOMO energy level of the Py-DB HTM provides efficient hole extraction with reduced energy loss at the perovskite/HTM interface. Consequently, an impressive power conversion efficiency (PCE) of 24.33 % was achieved for dopant-free Py-DB-based PSCs, which is the highest PCE for dopant-free small molecular HTMs in n-i-p configured PSCs. The dopant-free Py-DB-based device also exhibits improved long-term stability, retaining over 90 % of its initial efficiency after 1000â h exposure to 25 % humidity at 60 °C. These findings provide valuable insights and approaches for the further development of dopant-free HTMs for efficient and reliable PSCs.
ABSTRACT
The CRISPR/Cas systems offer a programmable platform for nucleic acid detection, and CRISPR/Cas-based diagnostics (CRISPR-Dx) have demonstrated the ability to target nucleic acids with greater accuracy and flexibility. However, due to the configuration of the reporter and the underlying labeling mechanism, almost all reported CRISPR-Dx rely on a single-option readout, resulting in limitations in end-point result readouts. This is also associated with high reagent consumption and delays in diagnostic reports due to protocol differences. Herein, we report for the first time a rationally designed Cas12a-based multimodal universal reporter (CAMURE) with improved sensitivity that harnesses a dual-mode reporting system, facilitating options in end-point readouts. Through systematic configurations and optimizations, our novel universal reporter achieved a 10-fold sensitivity enhancement compared to the DETECTR reporter. Our unique and versatile reporter could be paired with various readouts, conveying the same diagnostic results. We applied our novel reporter for the detection of staphylococcal enterotoxin A due to its high implication in staphylococcal food poisoning. Integrated with loop-mediated isothermal amplification, our multimodal reporter achieved 10 CFU/mL sensitivity and excellent specificity using a real-time fluorimeter, in-tube fluorescence, and lateral flow strip readouts. We also propose, using artificially contaminated milk samples, a fast (2-5 min) Triton X-100 DNA extraction approach with a comparable yield to the commercial extraction kit. Our CAMURE could be leveraged to detect all gene-encoding SEs by simply reprogramming the guide RNA and could also be applied to the detection of other infections and disease biomarkers.
Subject(s)
CRISPR-Cas Systems , Nucleic Acids , CRISPR-Cas Systems/genetics , Biological Assay , Octoxynol , Nucleic Acid Amplification TechniquesABSTRACT
BACKGROUND: Studies have demonstrated that Sorting nexin 7 (SNX7) functions as an anti-apoptotic protein in liver tissue and plays a crucial role in the survival of hepatocytes during early embryonic development. However, its diagnostic and prognostic value as well as the predictive value of chemotherapy and immunotherapy have not been reported in hepatocellular carcinoma (HCC). METHODS: SNX7 mRNA expression and its diagnostic efficacy were examined in GEO datasets, and the findings were further confirmed in TCGA, ICGC cohorts, and cell lines. The protein level of SNX7 was determined using CPTAC and HPA databases, and the results were validated through immunohistochemistry (IHC). Survival analyses were performed in TCGA and ICGC cohorts, and the results were subsequently validated via Kaplan-Meier Plotter. The response to chemotherapy and immunotherapy was predicted via GDSC dataset and TIDE algorithm, respectively. R packages were employed to explore the relationship between SNX7 expression and immune infiltration, m6A modification, as well as the functional enrichment of differentially expressed genes (DEGs). RESULTS: The expression of SNX7 at both mRNA and protein levels was significantly upregulated in HCC tissues. SNX7 exhibited superior diagnostic efficacy compared to AFP alone for HCC detection, and combining it with AFP improved the diagnostic accuracy for HCC. High SNX7 was associated with unfavorable outcomes, including poor overall survival, disease-specific survival, progression-free survival, and advanced pathological stage, in patients with HCC, and SNX7 was identified as an independent risk factor for HCC. Moreover, elevated SNX7 expression was positively correlated with increased sensitivity to various chemotherapy drugs, including sorafenib, while it was associated with resistance to immunotherapy in HCC patients. Correlation analysis revealed a relationship between SNX7 and multiple m6A-related genes and various immune cells. Finally, enrichment analysis demonstrated strong associations of SNX7 with critical biological processes, such as cell cycle regulation, cellular senescence, cell adhesion, DNA replication, and mismatch repair pathway in HCC. CONCLUSIONS: Our study highlights the association of SNX7 with the immune microenvironment and its potential influence on HCC progression. SNX7 emerges as a promising novel biomarker for the diagnosis, prognosis, and prediction of response to chemotherapy and immunotherapy in patients with HCC.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Female , Pregnancy , Humans , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/genetics , alpha-Fetoproteins , Liver Neoplasms/diagnosis , Liver Neoplasms/drug therapy , Liver Neoplasms/genetics , Prognosis , Biomarkers , Immunotherapy , Tumor MicroenvironmentABSTRACT
The pathogenesis of inflammatory bowel diseases (IBDs) including ulcerative colitis (UC) and Crohn's disease is extremely cloudy. Maintaining the level of remission lesions in colitis is the default treatment attitude at present. Epithelial barrier restoration is considered as the same important strategy as colonic targeted drug delivery in UC treatment. In this paper, we developed a multilayer natural polysaccharide microsphere (pectin/chitosan/alginate) with pH and enzyme dual sensitivity to reduce the loss of medication in the upper digestive tract and preferentially adhere to exposed epithelial cells in colonic tissues by electrostatic forces for efficiently targeted UC treatment. Olsalazine as an inflammatory drug was efficiently loaded in the chitosan layer and realized a colonic pH-responsive drug release. Furthermore, the multilayer microspheres exhibited excellent capability in suppressing harmful flora and a bio-adhesion effect to extend the duration of local medicine. In the in vivo anti-colitis study, the downregulated levels of pro-inflammatory factors and the increase of tight junction protein indicated the excellent anti-inflammation effect of the olsalazine-loaded microspheres. In summary, these results showed that the multilayer natural polysaccharide microspheres could be a powerful candidate in the targeted drug delivery system for UC therapy.
Subject(s)
Chitosan , Colitis, Ulcerative , Humans , Colitis, Ulcerative/drug therapy , Chitosan/therapeutic use , Microspheres , Alginates , PectinsABSTRACT
Nocardia seriolae is the main pathogen of fish nocardiosis. In our previous study, alanine dehydrogenase was identified as a potential virulence factor of N. seriolae. On the basis of this fact, the alanine dehydrogenase gene of N. seriolae (NsAld) was knocked out to establish the strain ΔNsAld for vaccine development against fish nocardiosis in this study. The LD50 of strain ΔNsAld was 3.90 × 105 CFU/fish, higher than that of wild strain (5.28 × 104 CFU/fish) significantly (p < 0.05). When the strain ΔNsAld was used as a live vaccine to immunize hybrid snakehead (Channa maculata â × Channa argus â) at 2.47 × 105 CFU/fish by intraperitoneal injection, the non-specific immune indexes (LZM, CAT, AKP, ACP and SOD activities), specific antibody (IgM) titers and several immune-related genes (CD4, CD8α, IL-1ß, MHCIα, MHCIIα and TNFα) were up-regulated in different tissues, indicating that this vaccine could induce humoral and cell-mediated immune responses. Furthermore, the relative percentage survival (RPS) of ΔNsAld vaccine was calculated as 76.48% after wild N. seriolae challenge. All these results suggest that the strain ΔNsAld could be a potential candidate for live vaccine development to control fish nocardiosis in aquaculture.
Subject(s)
Fish Diseases , Nocardia Infections , Animals , Alanine Dehydrogenase/genetics , Gene Deletion , Nocardia Infections/prevention & control , Nocardia Infections/veterinary , Nocardia Infections/genetics , Fishes/genetics , Vaccine DevelopmentABSTRACT
The mucosal microbiome plays a role in regulating host health. The research conducted in humans and mice has governed and detailed the information on microbiome-host immunity interactions. Teleost fish, different from humans and mice, lives in and relies on the aquatic environment and is subjected to environmental variation. The growth of teleost mucosal microbiome studies, the majority in the gastrointestinal tract, has emphasized the essential role of the teleost microbiome in growth and health. However, research in the teleost external surface microbiome, as the skin microbiome, has just started. In this review, we examine the general findings in the colonization of the skin microbiome, how the skin microbiome is subjected to environmental change and the reciprocal regulation with the host immune system, and the current challenges that potential study models can address. The information collected from teleost skin microbiome-host immunity research would help future teleost culturing from the potential parasitic infestation and bacterial infection as foreseeing growing threats.
Subject(s)
Bacterial Infections , Microbiota , Humans , Animals , Mice , Skin , Mucous Membrane , Gastrointestinal TractABSTRACT
PURPOSE: Mutations in the ß-tubulin isotype, TUBB8, can cause female infertility. Although several mutations of TUBB8 have been reported, the full spectrum for guiding genetics counseling still needs to be further explored. Here, we sought to identify novel variants in TUBB8 and their phenotypic effects on microtubule network structure in vitro. METHODS: Whole-exome sequence analysis was performed in two families with infertility to detect pathogenic variants, with validation by Sanger sequencing. All gene variants and protein structures were predicted in silico. Cells were transfected with wild-type and mutants, and immunofluorescence analysis was performed to visualize microtubule network changes. RESULTS: We detected a novel compound heterozygous mutation, c.915_916delCC (p.Arg306Serfs*21) and c.82C > T (p.His28Tyr), and a benign heterozygous variant c.1286C > T (p.Thr429Met) in TUBB8 in the two families. Female patients with p.Arg306Serfs*21 and p.His28Tyr were infertile with early embryonic developmental arrest. The female patient with p.Thr429Met gave birth to a healthy baby in the second in vitro fertilization frozen embryo transfer cycle. The p.Arg306Serfs*21 mutation was predicted to cause large structural alteration in the TUBB8 protein and was confirmed to produce a truncated and trace protein by western blot analysis. Immunofluorescence analysis of transfected HeLa cells showed that p.Arg306Serfs*21 significantly disrupted microtubule structure. CONCLUSIONS: Our findings expand the known mutational spectrum of TUBB8 associated with early embryonic developmental arrest and female infertility.
Subject(s)
Infertility, Female , Oocytes , Humans , Female , Oocytes/metabolism , Infertility, Female/genetics , Infertility, Female/metabolism , HeLa Cells , Mutation/genetics , Microtubules/genetics , Tubulin/geneticsABSTRACT
In this paper, we report a multi-ring disk resonator with elliptic spokes for compensating the aniso-elasticity of (100) single crystal silicon. The structural coupling between each ring segments can be controlled by replacing the straight beam spokes with the elliptic spokes. The degeneration of two n = 2 wineglass modes could be realized by optimizing the design parameters of the elliptic spokes. The mode-matched resonator could be obtained when the design parameter, aspect ratio of the elliptic spokes was 25/27. The proposed principle was demonstrated by both numerical simulation and experiment. A frequency mismatch as small as 1330 ± 900 ppm could be experimentally demonstrated, which was much smaller than that of the conventional disk resonator, which achieved as high as 30,000 ppm.
ABSTRACT
Tartrate-resistant acid phosphatase type 5 (TRAP5) is an enzyme that is highly expressed in activated macrophages and osteoclasts and plays important biological functions in mammalian immune defense systems. In the study, we investigated the functions of tartrate-resistant acid phosphatase type 5b from Oreochromis niloticus (OnTRAP5b). The OnTRAP5b gene has an open reading frame of 975 bp, which encodes a mature peptide consisting of 302 amino acids with a molecular weight of 33.448 kDa. The OnTRAP5b protein contains a metallophosphatase domain with metal binding and active sites. Phylogenetic analysis revealed that OnTRAP5b is clustered with TRAP5b of teleost fish and shares a high amino acid sequence similarity with other TRAP5b in teleost fish (61.73-98.15%). Tissues expression analysis showed that OnTRAP5b was most abundant in the liver and was also widely expressed in other tissues. Upon challenge with Streptococcus agalactiae and Aeromonas hydrophila in vivo and in vitro, the expression of OnTRAP5b was significantly up-regulated. Additionally, the purified recombinant OnTRAP5b ((r)OnTRAP5) protein exhibited optimal phosphatase activity at pH 5.0 and an ideal temperature of 50 °C. The Vmax, Km, and kcat of purified (r)OnTRAP5b were found to be 0.484 µmol × min-1 × mg-1, 2.112 mM, and 0.27 s-1 with respect to pNPP as a substrate, respectively. Its phosphatase activity was differentially affected by metal ions (K+, Na+, Mg2+, Ca2+, Mn2+, Cu2+, Zn2+, and Fe3+) and inhibitors (sodium tartrate, sodium fluoride, and EDTA). Furthermore, (r)OnTRAP5b was found to promote the expression of inflammatory-related genes in head kidney macrophages and induce reactive oxygen expression and phagocytosis. Moreover, OnTRAP5b overexpression and knockdown had a significant effect on bacterial proliferation in vivo. When taken together, our findings suggest that OnTRAP5b plays a significant role in the immune response against bacterial infection in Nile tilapia.
Subject(s)
Cichlids , Fish Diseases , Streptococcal Infections , Animals , Cichlids/genetics , Cichlids/microbiology , Immunity, Innate/genetics , Tartrate-Resistant Acid Phosphatase/genetics , Tartrate-Resistant Acid Phosphatase/metabolism , Phylogeny , Fish Proteins/metabolism , Streptococcal Infections/veterinary , Streptococcus agalactiae/genetics , Gene Expression Regulation , Mammals/metabolismABSTRACT
This study seeks to empirically explore the relation between multilingual learning experiences and language aptitude. Through employing LLAMA aptitude test battery (Meara, 2005) and a probabilistic version of the serial reaction time (SRT) task (Kaufman et al., 2010), scores from 24 Chinese-English bilinguals and 24 Tibetan-Chinese-English trilinguals were analyzed with One-way Analyses of Variance (ANOVA). LLAMA-B, E, and F sub-tests measured explicit language aptitude, while LLAMA-D sub-test and SRT task measured implicit language aptitude, a cutting-edge that has gained sway in aptitude research. Qualitative and quantitative results showed that trilingual group performed better on the LLAMA-E sub-test than bilingual group, whereas bilingual group outperformed trilingual group on the SRT task. These findings suggested that trilinguals might possess higher explicit aptitude but lower implicit aptitude than bilinguals. Thus, prior language learning experiences might be positively (for explicit aptitude) or negatively (for implicit aptitude) correlated with language aptitude. Additionally, explicit aptitude and implicit aptitude might have a competitive relationship. Possible implications were discussed in this article.
Subject(s)
Aptitude , Multilingualism , Humans , East Asian People , Tibet , LanguageABSTRACT
Hole transport materials (HTMs) are a key component of perovskite solar cells (PSCs). The small molecular 2,2',7,7'-tetrakis(N,N-di-p-methoxyphenyl)-amine-9,9'-spirobifluorene (spiro-OMeTAD, termed "Spiro") is the most successful HTM used in PSCs, but its versatility is imperfect. To improve its performance, we developed a novel spiro-type HTM (termed "DP") by substituting four anisole units on Spiro with 4-methoxybiphenyl moieties. By extending the π-conjugation of Spiro in this way, the HOMO level of the HTM matches well with the perovskite valence band, enhancing hole mobility and increasing the glass transition temperature. DP-based PSC achieves high power conversion efficiencies (PCEs) of 25.24 % for small-area (0.06â cm2 ) devices and 21.86 % for modules (designated area of 27.56â cm2 ), along with the certified efficiency of 21.78 % on a designated area of 27.86â cm2 . The encapsulated DP-based devices maintain 95.1 % of the initial performance under ISOS-L-1 conditions after 2560â hours and 87 % at the ISOS-L-3 conditions over 600â hours.
ABSTRACT
Sexually transmitted Chlamydia trachomatis can ascend to the upper genital tract due to its resistance to innate immunity in the lower genital tract. C. trachomatis can activate the cGAS-STING signaling pathway in cultured cells via either cGAS or STING. This study was designed to evaluate the role of the cGAS-STING pathway in innate immunity against C. trachomatis in the mouse genital tract. Following intravaginal inoculation, C. trachomatis significantly declined by day 5 following a peak infection on day 3, while the mouse-adapted Chlamydia muridarum continued to rise for >1 week, indicating that C. trachomatis is susceptible to the innate immunity in the female mouse genital tract. This conclusion was supported by the observation of a similar shedding course in mice deficient in adaptive immunity. Thus, C. trachomatis can be used to evaluate innate immunity in the female genital tract. It was found that mice deficient in either cGAS or STING significantly increased the yields of live C. trachomatis bacteria on day 5, indicating an essential role of the cGAS-STING signaling pathway in innate immunity of the mouse genital tract. Comparison of live C. trachomatis bacteria recovered from different genital tissues revealed that the cGAS-STING-dependent immunity against C. trachomatis was restricted to the mouse lower genital tract regardless of whether C. trachomatis was inoculated intravaginally or transcervically. Thus, we have demonstrated an essential role of the cGAS-STING signaling pathway in innate immunity against chlamydial infection, laying a foundation for further illuminating the mechanisms of the innate immunity in the female lower genital tract.
Subject(s)
Chlamydia Infections , Chlamydia trachomatis , Animals , Chlamydia Infections/microbiology , Female , Genitalia, Female/microbiology , Mice , Nucleotidyltransferases/genetics , Signal TransductionABSTRACT
Intravaginal infection of mice with Chlamydia muridarum has been used for investigating the mechanisms of Chlamydia trachomatis-induced pathogenicity and immune responses. In the current study, the mouse model was used to evaluate the impact of interleukin-27 (IL-27) and its receptor signaling on the susceptibility of the female genital tract to chlamydial infection. Mice deficient in IL-27 developed significantly shortened courses of chlamydial infection in the female genital tract. The titers of live Chlamydia recovered from the genital tract of IL-27-deficient mice declined significantly by day 7 following intravaginal inoculation. These observations suggest that IL-27 may promote chlamydial infection in the female mouse genital tract. This conclusion was validated using IL-27 receptor (R)-deficient mice. Further, the reduction in chlamydial burden corelated with the increase in gamma interferon (IFN-γ) and IL-17 in the genital tract tissues of the IL-27R-deificent mice. However, depletion of IFN-γ but not IL-17 from the IL-27R-deificent mice significantly increased the chlamydial burden, indicating that IL-27 may mainly suppress IFN-γ-mediated immunity for promoting chlamydial infection. Finally, knockout of IL-27R from T cells alone was sufficient for significantly shortening the infectious shedding courses of Chlamydia in the mouse genital tract. The above-described results have demonstrated that Chlamydia can activate IL-27R signaling in Th1-like cells for promoting its infection in the female genital tract, suggesting that attenuating IL-27 signaling in T cells may be used for enhancing genital tract immunity against chlamydial infection.