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Owing to the Fermi pinning effect arose in the metal electrodes deposition process, metal-semiconductor contact is always independent on the work function, which challenges the next-generation optoelectronic devices. In this work, a metal-assisted transfer approach is developed to transfer Bi2 O2 Se nanosheets onto the pre-deposited metal electrodes, benefiting to the tunable metal-semiconductor contact. The success in Bi2 O2 Se nanosheets transfer is contributed to the stronger van der Waals adhesion of metal electrodes than that of growth substrates. With the pre-deposited asymmetric electrodes, the self-powered near-infrared photodetectors are realized, demonstrating low dark current of 0.04 pA, high Ilight /Idark ratio of 380, fast rise and decay times of 4 and 6 ms, respectively, under the illumination of 1310 nm laser. By pre-depositing the metal electrodes on polyimide and glass, high-performance flexible and omnidirectional self-powered near-infrared photodetectors are achieved successfully. This study opens up new opportunities for low-dimensional semiconductors in next-generation high-performance optoelectronic devices.
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The intricate processes that govern the interactions between peripatetic immune cells and distal renal injury in obesity are not fully understood. Employing transcriptomic analysis of circulating extracellular vesicles (EVs), a marked amplification of small RNA (miR-3960) is discerned within CD3-CD19+ B cells. This RNA is found to be preferentially augmented in kidney tissues, contrasting with its subdued expression in other organs. By synthesizing dual-luciferase reporter assay with co-immunoprecipitation analysis, it is pinpointed that miR-3960 specifically targets the nuclear gene TRMT5, a pivotal actor in the methylation of mitochondrial tRNA. This liaison instigates aberrations in the post-transcriptional modifications of mitochondrial tRNA, engendering deficiencies within the electron respiratory chain, primarily attributable to the diminution of the mitochondrial bioenergetic compound (NDUFA7) complex I. Such perturbations lead to a compromised mitochondrial respiratory capacity in renal tubular cells, thereby exacerbating tubular injury. In contrast, EV blockade or miR-3960 depletion markedly alleviates renal tubular injury in obesity. This investigation unveils a hitherto unexplored pathway by which obesity-induced circulating immune cells remotely manipulate mitochondrial metabolism in target organs. The strategic targeting of obese EVs or infiltrative immune cells and their specifically secreted RNAs emerges as a promising therapeutic avenue to forestall obesity-related renal afflictions.
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BACKGROUND: Klebsiella pneumonia, a Gram-negative bacterium belonging to the genus Enterobacter, causes many human and livestock diseases. Notably, infected goats may develop pneumonia, septicemia, which can lead to occasional death, resulting in great economic losses in goat-farming industry. However, there are little systematic methods for detection of goat Klebsiella pneumoniae in livestock production. RESULTS: In this study, we developed a Klebsiella pneumoniae goat polyclonal antibody and established an indirect ELISA method to detect the Klebsiella pneumoniae. After screening and optimizing the conditions for detection, we determined the optimal working dilutions of the coated-bacterial antigen, the polyclonal antibody, and the enzyme-labeled secondary antibody that were 1:800 (2.99 × 107 CFU/ml), 1:6400, and 1:5000, respectively. The optimal condition of coating and blocking were both 4 °C for 12 h. The optimal dilution buffers of bacterial antigen, the antibodies, and the blocking buffer were 0.05 mol/L carbonate buffer, 1% BSA phosphate buffer, and 1.5% BSA carbonate buffer, respectively. The cut-off value was determined to be 0.28, and the analytical sensitivity was 1:800 (dilution of a positive sample). Furthermore, there was no cross-reaction between the coated antigen and goat serum positive for antibodies against other bacteria, indicating that indirect ELISA could detect Klebsiella pneumoniae specifically in most cases. The average coefficients of variation of intra-assay and inter-assay were 4.37 and 5.17% indicating favorable reproducibility of indirect ELISA. In the detection of clinical veterinary samples, the positive rate of indirect ELISA was 6.74%, higher than that of conventional agglutination assays. CONCLUSIONS: Taken together, we successfully established an indirect ELISA method for detecting antibodies against Klebsiella pneumoniae in goats, which can be applied in production.
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Anticorpos Antibacterianos/sangue , Infecções por Klebsiella/veterinária , Klebsiella pneumoniae/imunologia , Animais , Ensaio de Imunoadsorção Enzimática/métodos , Ensaio de Imunoadsorção Enzimática/veterinária , Doenças das Cabras/diagnóstico , Doenças das Cabras/microbiologia , Cabras , Infecções por Klebsiella/diagnóstico , Infecções por Klebsiella/imunologia , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: This study purposed to design and establish a nomogram to predict the risk of having heart failure with preserved ejection fraction. METHOD: The clinical data of 1031 patients diagnosed with heart failure (HF) in the First Affiliated Hospital of Jinan University from January 2018 to December 2022 were retrospectively analyzed, among which 618 patients were diagnosed with heart failure with preserved ejection fraction (HFpEF). Patients were randomly divided into a training set (70%, n = 722) and a validation set (30%, n = 309). The prediction model of HFpEF was established by using clinical characteristic data parameters, and the risk of having HFpEF was predicted by using a nomogram. Single-factor analysis was used to select independent risk factors (P < 0.05), and then binary logistic regression was used to screen predictive variables (P < 0.05). The discrimination ability of the model was evaluated by the ROC curve and calculating the area under the curve (AUC). In addition, the predictive ability of the established nomogram was evaluated using calibration curves and the Hosmer-Lemeshow goodness of fit test (HL test), and the clinical net benefit was evaluated using decision curve analysis (DCA). RESULTS: The results of binary logistic regression analysis showed that age, gender, hypertension, coronary heart disease, glycosylated hemoglobin, serum creatinine, E/e' septal, relative wall thickness (RWT), left ventricular mass index (LVMI) and pulmonary hypertension (PH) were independent influencing factors for the risk of having HFpEF (P < 0.05). Based on the results of logistic regression analysis, a nomogram was established and calibration curves were made. The prediction model showed that the AUC of the training dataset was 0.876 (95%CI, 0.851-0.902), and 0.837 (95%CI, 0.791-0.883) in the validation set. According to the calibration curves and HL test, the nomogram shows good calibration, and DCA shows that our model is clinically useful. CONCLUSION: A nomogram prediction model was constructed to predict the patient's risk of having HFpEF. This prediction model indicated that the combination of creatinine, E/e', RWT, LVMI and PH may be valuable in the diagnosis of HFpEF.
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Insuficiência Cardíaca , Nomogramas , Volume Sistólico , Humanos , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Masculino , Feminino , Volume Sistólico/fisiologia , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Medição de Risco/métodos , Valor Preditivo dos Testes , Fatores de RiscoRESUMO
Background: Tuberculosis (TB) persists as a global health challenge, with its treatment hampered by the side effects of long-term combination drug therapies and the growing issue of drug resistance. Therefore, the development of novel therapeutic strategies is critical. This study focuses on the role of immune checkpoint molecules (ICs) and functions of CD8+ T cells in the search for new potential targets against TB. Methods: We conducted differential expression genes analysis and CD8+ T cell functional gene analysis on 92 TB samples and 61 healthy individual (HI) samples from TB database GSE83456, which contains data on 34,603 genes. The GSE54992 dataset was used to validated the findings. Additionally, a cluster analysis on single-cell data from primates infected with mycobacterium tuberculosis and those vaccinated with BCG was performed. Results: The overexpression of LAG-3 gene was found as a potentially important characteristic of both pulmonary TB (PTB) and extrapulmonary TB (EPTB). Further correlation analysis showed that LAG-3 gene was correlated with GZMB, perforin, IL-2 and IL-12. A significant temporal and spatial variation in LAG-3 expression was observed in T cells and macrophages during TB infection and after BCG vaccination. Conclusion: LAG-3 was overexpressed in TB samples. Targeting LAG-3 may represent a potential therapeutic target for tuberculosis.
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Antígenos CD , Linfócitos T CD8-Positivos , Proteína do Gene 3 de Ativação de Linfócitos , Mycobacterium tuberculosis , Tuberculose , Humanos , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/genética , Linfócitos T CD8-Positivos/imunologia , Tuberculose/imunologia , Tuberculose/microbiologia , Animais , Antígenos CD/genética , Vacina BCG/imunologia , Macrófagos/imunologia , Macrófagos/microbiologia , Interleucina-2/metabolismo , Interleucina-2/genética , Perfilação da Expressão Gênica , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/microbiologia , Interleucina-12/genética , Interleucina-12/metabolismo , Perforina/genética , Perforina/metabolismo , MasculinoRESUMO
Immune Checkpoint Inhibitors (ICIs) therapy has advanced significantly in treating malignant tumors, though most 'cold' tumors show no response. This resistance mainly arises from the varied immune evasion mechanisms. Hence, understanding the transformation from 'cold' to 'hot' tumors is essential in developing effective cancer treatments. Furthermore, tumor immune profiling is critical, requiring a range of diagnostic techniques and biomarkers for evaluation. The success of immunotherapy relies on T cells' ability to recognize and eliminate tumor cells. In 'cold' tumors, the absence of T cell infiltration leads to the ineffectiveness of ICI therapy. Addressing these challenges, especially the impairment in T cell activation and homing, is crucial to enhance ICI therapy's efficacy. Concurrently, strategies to convert 'cold' tumors into 'hot' ones, including boosting T cell infiltration and adoptive therapies such as T cell-recruiting bispecific antibodies and Chimeric Antigen Receptor (CAR) T cells, are under extensive exploration. Thus, identifying key factors that impact tumor T cell infiltration is vital for creating effective treatments targeting 'cold' tumors.
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Anticorpos Biespecíficos , Neoplasias , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias/tratamento farmacológico , Linfócitos T , Imunoterapia/métodosRESUMO
Realizing omnidirectional self-powered photodetectors is central to advancing next-generation portable and smart photodetector systems. However, the traditional omnidirectional photodetector is typically achieved by integrating complex hemispherical microlens on multiple photodetectors, which makes the detection system cumbersome and restricts its application in the portable field. Here, facile and high-performance flexible omnidirectional self-powered photodetectors are achieved by solution-processed two-dimensional (2D) layered PbI2 nanoplates on transparent conducting substrates. Characterization of PbI2 nanoplates microstructural/compositional and their photodetection properties have been systematically characterized. Under the irradiation of a 405 nm laser, the photodetectors exhibit an impressively low dark current of 10-13 A, a high light on/off ratio up to 106, and a fast rise/decay response time of 2/3 ms. Importantly, when light irradiates the photodetector at 5°, it can still maintain high photodetection properties, realizing almost 360° omnidirectional self-powered photodetection. What is more, these self-powered photodetectors exhibit robust omnidirectional photoresponse stability of flexibility even after bending for 1200 cycles. Thus, this work broadens the applicability of 2D layered nanoplates for further extending its applications in advanced optoelectronic devices.
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Based on social cognitive theory, we studied the relationship between coaches' paternalistic leadership (PL) and youth athletes' organizational citizenship behavior (OCB) and the mediation effect of athletes' trust in coaches, in China. This age-specific research was conducted among more than 2,000 Chinese youth soccer players. Overall, 758 youth soccer players, aged 13-18 years, completed a self-report questionnaire. The results showed that the three dimensions of the coaches' PL have different relationships with OCB, and the differences were due to differences in athletes' ages. Additionally, we verified the mediation role of trust. Our research conclusions are of great significance to the study of Chinese youth soccer as in-depth research can provide a deeper and more precise understanding of the relationship between PL and the OCB of Chinese youth soccer players. This study expands the literature on social cognitive theory and sheds light on the relationship between coach leadership and athlete OCB by providing extensive evidence.
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Intestinal mucosa is the largest immune organ in animals, and its immune function is directly related to the resistance against various diseases. Taishan Pinus massoniana pollen polysaccharides (TPPPS) have been recognized as an effective vaccine adjuvant and potential immune enhancer against viral infections. However, little is known about their direct immune-enhancing activity on intestinal mucosa. In this study, we extracted the polysaccharides from Taishan masson pine pollen to investigate its promotive effect on intestinal mucosal immunity. A total of 120 1-day-old chickens were divided into 4 groups and inoculated with PBS or 3 different doses of TPPPS (10 mg/mL, 20 mg/mL, and 40 mg/mL), respectively. Feces, intestinal specimens, and serum samples were collected from the chickens at 7, 14, and 21 d after inoculation. The antibodies in serum, mucosal secretion of IgA, structure of intestinal villi, and expressions of cytokine genes and mucosal immune-related genes in the chickens were all significantly improved by TPPPS treatments. At 21 d after inoculation following the challenge of Newcastle disease virus, the chickens inoculated with 20 and 40 mg/mL TPPPS exhibited decreased weight loss and reduced intestinal pathologic damage and viral loads in the intestine. In summary, our results demonstrate that TPPPS can enhance mucosal immunity and promote intestinal villi development. This study has established the foundation for the development of novel immune-enhancing agent with immune-regulatory effects on intestinal mucosa.
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Galinhas/imunologia , Imunidade nas Mucosas/efeitos dos fármacos , Mucosa Intestinal/imunologia , Pinus , Pólen/química , Polissacarídeos/farmacologia , Animais , Citocinas/análise , Imunoglobulina A Secretora/análise , Imunoglobulina G/sangue , Distribuição Aleatória , Organismos Livres de Patógenos EspecíficosRESUMO
The objective was to identify the active fractions of polysaccharide against replication of ALV-J and elucidate their structure activity relationship. The optimal extraction conditions were extracting temperature 90â, pH 9 and the ratio of liquid to solid 30:1. Under these conditions, extraction yield of total polysaccharide was 6.5 % ± 0.19 %. Total polysaccharide was then purified by DEAE-52 cellulose and Sephadex G-200 gel. Three fractions, PPP-1, PPP-2, and PPP-3, were identified with molecular weight of 463.70, 99.41, and 26.97 kDa, respectively. Three polysaccharide fractions were all composed of 10 monosaccharides in different proportions. Compared with PPP-1, which was mainly composed of glucose, PPP-2 and PPP-3 contained a higher proportion of galactose, glucuronic acid and galacturonic acid. The Congo red assay indicated that the PPP-2 may have a triple helical structure, while PPP-1 and PPP-3 were absent. In vitro assay showed that there was no significant cytotoxicity among the polysaccharide fractions under the concentration of 800 µg mL-1 (P > 0.05). The antiviral test showed that PPP-2 had the strongest activity, indicating PPP-2 was the major antiviral component. The structure-activity relationship showed that the antiviral activities of polysaccharide fractions were affected by their monosaccharide composition, molecular weight, and triple helical structure, which was a result of a combination of multiple molecular structural factors. These results showed that the PPP-2 could be exploited as a valued product for replacing synthetic antiviral drugs, and provided support for future applications of polysaccharide from Pinus massoniana pollen as a useful source for antiviral agent.
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Antivirais/farmacologia , Vírus da Leucose Aviária/efeitos dos fármacos , Leucose Aviária/tratamento farmacológico , Pinus/química , Polissacarídeos/farmacologia , Replicação Viral/efeitos dos fármacos , Animais , Antivirais/química , Antivirais/isolamento & purificação , Leucose Aviária/virologia , Vírus da Leucose Aviária/fisiologia , Linhagem Celular , Embrião de Galinha , Monossacarídeos/química , Monossacarídeos/isolamento & purificação , Monossacarídeos/farmacologia , Pólen/química , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
The stability of the intestinal microenvironment is the basis for maintaining the normal physiological activities of the intestine. On the contrary, disordered dynamic processes lead to chronic inflammation and disease pathology. Pinus massoniana pollen polysaccharide (PPPS), isolated from Taishan Pinus massoniana pollen, has been reported with extensive biological activities, including immune regulation. However, the role of PPPS in the intestinal microenvironment and intestinal diseases is still unknown. In this work, we initiated our investigation by using 16S rRNA high-throughput sequencing technology to assess the effect of PPPS on gut microbiota in mice. The result showed that PPPS regulated the composition of gut microbiota in mice and increased the proportion of probiotics. Subsequently, we established immunosuppressive mice using cyclophosphamide (CTX) and found that PPPS regulated the immunosuppressive state of lymphocytes in Peyer's patches (PPs). Moreover, PPPS also regulated systemic immunity by acting on intestinal PPs. PPPS alleviated lipopolysaccharide (LPS) -induced Caco2 cell damage, indicating that PPPS has the ability to reduce the damage and effectively improve the barrier dysfunction in Caco2 cells. In addition, PPPS alleviated colonic injury and relieved colitis symptoms in dextran sodium sulfate (DSS)-induced colitis mice. Overall, our findings indicate that PPPS shows a practical regulatory effect in the intestinal microenvironment, which provides an essential theoretical basis for us to develop the potential application value of PPPS further.
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Colite/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Pinus/imunologia , Pólen/imunologia , Polissacarídeos/imunologia , Polissacarídeos/farmacologia , Animais , Colite/imunologia , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
The H9N2 subtype avian influenza virus (AIV) is one of the most prevalent AIV subtypes that can be found throughout most countries. Currently, due to the neglect of low pathogenic avian influenza virus (LPAIV) and monotonous control technique, an expanding H9N2 virus epizootic have been arisen and causes great economic losses in the poultry industry. Therefore, novel anti-influenza drugs are necessary for the prevention and control of H9N2 AIV. Our previous studies have found that Taishan Pinus massoniana pollen polysaccharides (TPPPS) have antiviral effects, but whether they can inhibit the H9N2 AIV remains unclear. Here, we further investigated the effects of TPPPS on the H9N2 virus and its underlying mechanisms of action. We found that TPPPS significantly inhibited the replication of the H9N2 virus in a dose-dependent manner, especially during the period of virus adsorption in vitro. Transmission electron microscopy demonstrated that TPPPS reduce infection by interfering with virus entry into host cells rather than by interacting with the H9N2 virus particles. A fluorescence quantitative PCR (qPCR) assay and an animal experiment were performed to evaluate the anti-viral effect of TPPPS in vivo. As expected, the lungs of chickens treated with TPPPS had fewer lesions and lower virus contents compared with the PBS group. In addition, pre-treatment with TPPPS clearly enhanced host disease resistance and delayed infection by the H9N2 virus. Taken together, our results reveal that TPPPS suppress H9N2 virus replication both in vitro and in vivo and therefore shows promising as an anti-AIV agent.
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Antivirais/uso terapêutico , Vírus da Influenza A Subtipo H9N2/efeitos dos fármacos , Pinus/química , Pólen/química , Polissacarídeos/uso terapêutico , Administração Oral , Animais , Anticorpos Antivirais/sangue , Galinhas/virologia , Cães , Influenza Aviária/tratamento farmacológico , Influenza Aviária/prevenção & controle , Células Madin Darby de Rim Canino , Doenças das Aves Domésticas/tratamento farmacológico , Doenças das Aves Domésticas/prevenção & controle , Doenças das Aves Domésticas/virologia , Carga Viral , Internalização do Vírus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacosRESUMO
H9N2 subtype low pathogenicity avian influenza virus (LPAIV) is distributed worldwide and causes enormous economic losses in the poultry industry. Despite immunization of almost all chickens with inactivated vaccines, the disease still remains widespread. We speculated that improving mucosal or cellular immune responses could contribute to improved control of H9N2 viruses. In this study, we constructed a novel Lactococcus lactis (L. lactis) strain expressing a recombinant fusion protein consisting of the M1 and HA2 proteins derived from an antigenically conserved endemic H9N2 virus strain. The M1-HA2 fusion protein was cloned downstream of a gene encoding a secretory peptide, and we subsequently confirmed that the fusion protein was secreted from L. lactis by Western blotting. We assessed the immunogenicity and protective effects of this recombinant L. lactis strain. Eighty 1-day-old chickens were divided into four groups, and the experimental groups were orally vaccinated twice with the recombinant L. lactis strain. Fecal and intestinal samples, sera, and bronchoalveolar lavage fluid were collected at 7, 14, and 21 days post-vaccination (dpv). Chickens vaccinated with the recombinant L. lactis strain showed significantly increased levels of serum antibodies, T cell-mediated immune responses, and mucosal secretory IgA (SIgA). Following challenge with H9N2 virus at 21 dpv, chickens vaccinated with the recombinant L. lactis strain showed decreased weight loss, lower viral titers in the lung, and reduced lung pathological damage. In summary, our results demonstrated that a recombinant L. lactis strain expressing an H9N2 M1-HA2 fusion protein could induce protective mucosal and systemic immunity. This oral vaccine is H9N2 virus-specific and represents a significant design improvement compared with previous studies. Our study provides a theoretical basis for improving mucosal immune responses to prevent and control H9N2 virus infection.