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Most aggregation-induced emission (AIE) luminogens exhibit high brightness, excellent photostability, and good biocompatibility, but these AIE-active agents, which kill two birds with one stone to result in applications in both stimulated emission depletion (STED) super-resolution imaging and photodynamic therapy (PDT), have not been reported yet but are urgently needed. To meet the requirements of STED nanoscopy and PDT, D-A-π-A-D type DTPABT-HP is designed by tuning conjugated π spacers. It exhibits red-shifted emission, high PLQY of 32.04%, and impressive 1O2 generation (9.24 fold compared to RB) in nanoparticles (NPs). Then, DTPABT-HP NPs are applied in cell imaging via STED nanoscopy, especially visualizing the dynamic changes of lysosomes in the PDT process at ultrahigh resolution. After that, in vivo PDT was also conducted by DTPABT-HP NPs, resulting in significantly inhibited tumor growth, with an inhibition rate of 86%. The work here is beneficial to the design of multifunctional agents and the deep understanding of their phototheranostic mechanism in biological research.
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Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotosensibilizantes/uso terapéutico , Diagnóstico por Imagen , Neoplasias/tratamiento farmacológico , Fotoquimioterapia/métodosRESUMEN
BACKGROUND: The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) serves as a novel composite lipid indicator for atherosclerosis. However, the association between NHHR and mortality in patients with diabetes or prediabetes remains unclear. Consequently, the objective of this study was to investigate the relationship between NHHR and both all-cause and cardiovascular mortality in US adults with diabetes or prediabetes. METHODS: This study included 12,578 adult participants with diabetes or prediabetes from the US National Health and Nutrition Examination Survey (1999-2018). Mortality outcomes were ascertained by linking to the National Death Index (NDI) record up to December 31, 2019. We employed a weighted multivariate Cox proportional hazards model and restricted cubic splines to assess the associations between NHHR and all-cause and cardiovascular mortality. A segmented Cox proportional hazards model was used for evaluating threshold effects. Furthermore, a competing risks analysis was performed to explore the relationship between NHHR and cardiovascular mortality. RESULTS: During a median follow-up period of 8.08 years, 2403 participants encountered all-cause mortality, with 662 of them specifically succumbing to cardiovascular mortality. The restricted cubic splines revealed a U-shaped association between NHHR and all-cause mortality, while an L-shaped association was observed for cardiovascular mortality. The analysis of threshold effects revealed that the inflection points for NHHR and all-cause and cardiovascular mortality were 2.72 and 2.83, respectively. Specifically, when the baseline NHHR was below the inflection points, a negative correlation was observed between NHHR and both all-cause mortality (HR: 0.76, 95% CI: 0.68-0.85) and cardiovascular mortality (HR: 0.70, 95% CI: 0.57-0.85). Conversely, when the baseline NHHR exceeded the inflection points, a positive correlation was observed between NHHR and both all-cause mortality (HR: 1.11, 95% CI: 1.06-1.16) and cardiovascular mortality (HR: 1.08, 95% CI: 1.00-1.16). CONCLUSIONS: Among US adults with diabetes or prediabetes, a U-shaped association was observed between NHHR and all-cause mortality, whereas an L-shaped association was identified with cardiovascular mortality. The inflection points for all-cause and cardiovascular mortality were 2.72 and 2.83, respectively.
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Enfermedades Cardiovasculares , Diabetes Mellitus , Encuestas Nutricionales , Estado Prediabético , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estado Prediabético/sangre , Estado Prediabético/mortalidad , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/sangre , Adulto , Estados Unidos/epidemiología , Diabetes Mellitus/mortalidad , Diabetes Mellitus/sangre , HDL-Colesterol/sangre , Anciano , Modelos de Riesgos Proporcionales , Causas de MuerteRESUMEN
Light-emitting electrochemical cells (LECs) are kind of easily fabricated and low-cost light-emitting devices that can efficiently convert electric power to light energy. Compared with blue and green LECs, the performance of deep-red LECs is limited by the high non-radiative rate of emitters in long-wavelength region. While various organic emitters with deep-red emission have been developed to construct high-performance LECs, including polymers, metal complexes, and organic luminous molecules (OLMs), but this is seldom summarized. Therefore, we overview the recent advances of organic emitters with emission at the deep-red region for LECs, and specifically highlight the molecular design approach and electrochemiluminescence performance. We hope that this review can act as a reference for further research in designing high-performance deep-red LECs.
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In this paper, ultra-sensitive and highly selective Hg2+ detection in aqueous solutions was studied by free-standing silicon nanowire (SiNW) sensors. The all-around surface of SiNW arrays was functionalized with (3-Mercaptopropyl)trimethoxysilane serving as Hg2+ sensitive layer. Due to effective electrostatic control provided by the free-standing structure, a detection limit as low as 1 ppt was obtained. A linear relationship (R 2 = 0.9838) between log(CHg2+ ) and a device current change from 1 ppt to 5 ppm was observed. Furthermore, the developed SiNW sensor exhibited great selectivity for Hg2+ over other heavy metal ions, including Cd2+. Given the extraordinary ability for real-time Hg2+ detection, the small size and low cost of the SiNW device, it is expected to be a potential candidate in field detection of environmentally toxic mercury.
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A direct, rapid, highly sensitive and specific biosensor for detection of cancer biomarkers is desirable in early diagnosis and prognosis of cancer. However, the existing methods of detecting cancer biomarkers suffer from poor sensitivity as well as the requirement of enzymatic labeling or nanoparticle conjugations. Here, we proposed a two-channel PDMS microfluidic integrated CMOS-compatible silicon nanowire (SiNW) field-effect transistor arrays with potentially single use for label-free and ultrasensitive electrical detection of cancer biomarkers. The integrated nanowire arrays showed not only ultrahigh sensitivity of cytokeratin 19 fragment (CYFRA21-1) and prostate specific antigen (PSA) with detection to at least 1 fg/mL in buffer solution but also highly selectivity of discrimination from other similar cancer biomarkers. In addition, this method was used to detect both CYFRA21-1 and PSA real samples as low as 10 fg/mL in undiluted human serums. With its excellent properties and miniaturization, the integrated SiNW-FET device opens up great opportunities for a point-of-care test (POCT) for quick screening and early diagnosis of cancer and other complex diseases.
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Antígenos de Neoplasias/análisis , Biomarcadores de Tumor/análisis , Calicreínas/análisis , Queratina-19/análisis , Técnicas Analíticas Microfluídicas , Nanocables/química , Neoplasias/química , Antígeno Prostático Específico/análisis , Silicio/química , Humanos , Técnicas Analíticas Microfluídicas/instrumentación , Neoplasias/diagnósticoRESUMEN
MicroRNAs (miRNAs) have been regarded as promising biomarkers for the diagnosis and prognosis of early-stage cancer as their expression levels are associated with different types of human cancers. However, it is a challenge to produce low-cost miRNA sensors, as well as retain a high sensitivity, both of which are essential factors that must be considered in fabricating nanoscale biosensors and in future biomedical applications. To address such challenges, we develop a complementary metal oxide semiconductor (CMOS)-compatible SiNW-FET biosensor fabricated by an anisotropic wet etching technology with self-limitation which provides a much lower manufacturing cost and an ultrahigh sensitivity. This nanosensor shows a rapid (< 1 minute) detection of miR-21 and miR-205, with a low limit of detection (LOD) of 1 zeptomole (ca. 600 copies), as well as an excellent discrimination for single-nucleotide mismatched sequences of tumor-associated miRNAs. To investigate its applicability in real settings, we have detected miRNAs in total RNA extracted from lung cancer cells as well as human serum samples using the nanosensors, which demonstrates their potential use in identifying clinical samples for early diagnosis of cancer.
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Neoplasias Pulmonares/diagnóstico , MicroARNs/análisis , MicroARNs/genética , Nanocables/química , Silicio/química , Transistores Electrónicos , Disparidad de Par Base/genética , Secuencia de Bases , Biomarcadores de Tumor/análisis , Técnicas Biosensibles/instrumentación , Conductividad Eléctrica , Diseño de Equipo , Análisis de Falla de Equipo , Humanos , Neoplasias Pulmonares/genética , Datos de Secuencia Molecular , Nanocables/ultraestructura , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Análisis de Secuencia de ARN/métodos , Coloración y Etiquetado , Células Tumorales CultivadasRESUMEN
Silicon nanowire field-effect transistors (SiNW-FETs) have recently emerged as a type of powerful nanoelectronic biosensors due to their ultrahigh sensitivity, selectivity, label-free and real-time detection capabilities. Here, we present a protocol as well as guidelines for detecting DNA with complementary metal oxide semiconductor (CMOS) compatible SiNW-FET sensors. SiNWs with high surface-to-volume ratio and controllable sizes were fabricated with an anisotropic self-stop etching technique. Probe DNA molecules specific for the target DNA were covalently modified onto the surface of the SiNWs. The SiNW-FET nanosensors exhibited an ultrahigh sensitivity for detecting the target DNA as low as 1 fM and good selectivity for discrimination from one-base mismatched DNA.
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Técnicas Biosensibles/métodos , ADN/química , Nanocables/química , Silicio/química , ADN/aislamiento & purificación , Sondas de ADN , Semiconductores , Transistores ElectrónicosRESUMEN
Herein, we describe a novel approach for rapid, label-free and specific DNA detection by applying rolling circle amplification (RCA) based on silicon nanowire field-effect transistor (SiNW-FET) for the first time. Highly responsive SiNWs were fabricated with a complementary metal oxide semiconductor (CMOS) compatible anisotropic self-stop etching technique which eliminated the need for hybrid method. The probe DNA was immobilized on the surface of SiNW, followed by sandwich hybridization with the perfectly matched target DNA and RCA primer that acted as a primer to hybridize the RCA template. The RCA reaction created a long single-stranded DNA (ssDNA) product and thus enhanced the electronic responses of SiNW significantly. The signal-to-noise ratio (SNR) as a figure-of-merit was analyzed to estimate the signal enhancement and possible detection limit. The nanosensor showed highly sensitive concentration-dependent conductance change in response to specific target DNA sequences. Because of the binding of an abundance of repeated sequences of RCA products, the SNR of >20 for 1 fM DNA detection was achieved, implying a detection floor of 50 aM. This RCA-based SiNW biosensor also discriminated perfectly matched target DNA from one-base mismatched DNA with high selectivity due to the substantially reduced nonspecific binding onto the SiNW surface through RCA. The combination of SiNW FET sensor with RCA will increase diagnostic capacity and the ability of laboratories to detect unexpected viruses, making it a potential tool for early diagnosis of gene-related diseases.
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Técnicas Biosensibles/métodos , ADN de Cadena Simple/aislamiento & purificación , Nanocables/química , Virus/aislamiento & purificación , Replicación del ADN , ADN de Cadena Simple/química , Relación Señal-Ruido , Silicio/química , Virus/genéticaRESUMEN
Transition metal dichalcogenides (TMDCs), which are representative of two-dimensional (2D) semiconductors, have attracted tremendous attention over the last two decades. TMDCs are regarded as potential candidates in modern nano- and optoelectronic applications due to their unique crystal structures and outstanding electronic and optoelectronic properties. For practical use, 2D semiconductors need to be fabricated with diverse morphologies for integration into electronic devices and to perform different functionalities. Controlled patterning synthesis with programmable geometries is therefore highly desired. We review state-of-the-art strategies for the patterned growth of atomic layer TMDCs and their heterostructures, including additive manufacturing and subtractive manufacturing for patterning single TMDC materials and the introduction of other low-dimensional nanomaterials as growth templates or hetero-atoms for element conversion in patterning TMDC heterostructures. The optoelectronic and electronic applications of the as-grown monolayer TMDC patterns are introduced. Future challenges and the prospects for the patterned growth of 2D semiconductors are discussed based on present achievements.
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Technology for spatial multi-omics aids the discovery of new insights into cellular functions and disease mechanisms. Here we report the development and applicability of multi-omics in situ pairwise sequencing (MiP-seq), a method for the simultaneous detection of DNAs, RNAs, proteins and biomolecules at subcellular resolution. Compared with other in situ sequencing methods, MiP-seq enhances decoding capacity and reduces sequencing and imaging costs while maintaining the efficacy of detection of gene mutations, allele-specific expression and RNA modifications. MiP-seq can be integrated with in vivo calcium imaging and Raman imaging, which enabled us to generate a spatial multi-omics atlas of mouse brain tissues and to correlate gene expression with neuronal activity and cellular biochemical fingerprints. We also report a sequential dilution strategy for resolving optically crowded signals during in situ sequencing. High-throughput in situ pairwise sequencing may facilitate the multidimensional analysis of molecular and functional maps of tissues.
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Secuenciación de Nucleótidos de Alto Rendimiento , Animales , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Ratones , Encéfalo/metabolismo , Calcio/metabolismo , Genómica/métodos , MultiómicaRESUMEN
Silicon nanowire (SiNW) field effect transistors (FETs) have emerged as powerful sensors for ultrasensitive, direct electrical readout, and label-free biological/chemical detection. The sensing mechanism of SiNW-FET can be understood in terms of the change in charge density at the SiNW surface after hybridization. So far, there have been limited systematic studies on fundamental factors related to device sensitivity to further make clear the overall effect on sensing sensitivity. Here, we present an analytical result for our triangle cross-section wire for predicting the sensitivity of nanowire surface-charge sensors. It was confirmed through sensing experiments that the back-gated SiNW-FET sensor had the highest percentage current response in the subthreshold regime and the sensor performance could be optimized in low buffer ionic strength and at moderate probe concentration. The optimized SiNW-FET nanosensor revealed ultrahigh sensitivity for rapid and reliable detection of target DNA with a detection limit of 0.1 fM and high specificity for single-nucleotide polymorphism discrimination. In our work, enhanced sensing of biological species by optimization of operating parameters and fundamental understanding for SiNW FET detection limit was obtained.
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Técnicas Biosensibles/instrumentación , Nanocables , Ácidos Nucleicos/análisis , Transistores Electrónicos , Sondas de ADN/química , Sondas de ADN/genética , Nanotecnología , Hibridación de Ácido Nucleico , Concentración Osmolar , Silicio , Electricidad EstáticaRESUMEN
Background: Depression is an independent factor to predict the hospitalization and mortality in the chronic HF patients. Citalopram is known as an effective drug for depression treatment. Currently, there is no specific recommendation in the HF guidelines for the treatment of psychological comorbidity. In recent years, many studies have shown that the citalopram may be safe in treating of chronic HF with depression. Objective: To evaluate the efficacy and safety of the citalopram in the treatment of elderly chronic HF combined with depression. Methods: PubMed, EMBASE, Cochrane, Web of Science, CNKI, VIP, CBM, and Wanfang were searched from their inception to May 2022. In the treatment of elderly chronic HF combined with depression, randomized controlled studies of the citalopram were included. Independent screening and extraction of data information were conducted by two researchers, and the quality was assessed by the Cochrane bias risk assessment tool. Review manager 5.4.1 was employed for statistical analysis. Results: The results of meta-analysis prove that the citalopram treatment for depressed patients with chronic HF has a benefit for HAMD-24 (MD: -8.51, 95% CI: -10.15 to -6.88) and LVEF (MD: 2.42, 95% CI: 0.51 to 4.33). Moreover, the score of GDS decreases, and NT-proBNP (MD: -537.78, 95% CI: -718.03 to -357.54) is improved. However, the comparison with the control group indicates that there is no good effect on HAMD-17 (MD: -5.14, 95% CI: -11.60 to 1.32), MADRS (MD: -1.57, 95% CI: -3.47 to 0.32) and LVEDD (MD: -1.45, 95% CI: -3.65 to -0.76). No obvious adverse drug reactions were observed. Conclusion: Citalopram treatment for depressed patients with chronic HF has a positive effect on LVEF and NT-proBNP. It can alleviate HAMD-24 and GDS, but the relative benefits for LVEDD, HAMD-17 and MADRS still need to be verified.Systematic Review Registration: PROSPERO [CRD42021289917].
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Background: The development of distant metastasis (DM) results in poor prognosis of breast cancer (BC) patients, however, it is difficult to predict the risk of distant metastasis. Methods: Differentially expressed genes (DEGs) were screened out using GSE184717 and GSE183947. GSE20685 were randomly assigned to the training and the internal validation cohort. A signature was developed according to the results of univariate and multivariate Cox regression analysis, which was validated by using internal and external (GSE6532) validation cohort. Gene set enrichment analysis (GSEA) was used for functional analysis. Finally, a nomogram was constructed and calibration curves and concordance index (C-index) were compiled to determine predictive and discriminatory capacity. The clinical benefit of this nomogram was revealed by decision curve analysis (DCA). Finally, we explored the relationships between candidate genes and immune cell infiltration, and the possible mechanism. Results: A signature containing CD74 and TSPAN7 was developed according to the results of univariate and multivariate Cox regression analysis, which was validated by using internal and external (GSE6532) validation cohort. Mechanistically, the signature reflect the overall level of immune infiltration in tissues, especially myeloid immune cells. The expression of CD74 and TSPAN7 is heterogeneous, and the overexpression is positively correlated with the infiltration of myeloid immune cells. CD74 is mainly derived from myeloid immune cells and do not affect the proportion of CD8+T cells. Low expression levels of TSPAN7 is mainly caused by methylation modification in BC cells. This signature could act as an independent predictive factor in patients with BC (p = 0.01, HR = 0.63), and it has been validated in internal (p = 0.023, HR = 0.58) and external (p = 0.0065, HR = 0.67) cohort. Finally, we constructed an individualized prediction nomogram based on our signature. The model showed good discrimination in training, internal and external cohort, with a C-index of 0.742, 0.801, 0.695 respectively, and good calibration. DCA demonstrated that the prediction nomogram was clinically useful. Conclusion: A new immune infiltration related signature developed for predicting metastatic risk will improve the treatment and management of BC patients.
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Multifunctional metallacycles with solid-state emission are highly important in cancer therapy. Here, an aggregation-induced emission (AIE)-active metallacycle of DTPABT-MC-R is developed with efficient emission in the NIR region in the solid state (PLQYs = 4.92%). DTPABT-MC-R-based nanoparticles also display excellent photo-stability, and impressive photosensitive characteristics (ROS efficiency = 10.74%), finally leading to applications in cellular imaging and photodynamic therapy (PDT).
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Dermatitis Fototóxica , Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológicoRESUMEN
We herein report the design of a novel semiconducting silicon nanowire field-effect transistor (SiNW-FET) biosensor array for ultrasensitive label-free and real-time detection of nucleic acids. Highly responsive SiNWs with narrow sizes and high surface-to-volume-ratios were "top-down" fabricated with a complementary metal oxide semiconductor compatible anisotropic self-stop etching technique. When SiNWs were covalently modified with DNA probes, the nanosensor showed highly sensitive concentration-dependent conductance change in response to specific target DNA sequences. This SiNW-FET nanosensor revealed ultrahigh sensitivity for rapid and reliable detection of 1 fM of target DNA and high specificity single-nucleotide polymorphism discrimination. As a proof-of-concept for multiplex detection with this small-size and mass producible sensor array, we demonstrated simultaneous selective detection of two pathogenic strain virus DNA sequences (H1N1 and H5N1) of avian influenza.
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Técnicas Biosensibles/métodos , Nanocables/química , Ácidos Nucleicos/análisis , Silicio/química , Anisotropía , ADN Viral/química , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H5N1 del Virus de la Influenza A/genética , Nanopartículas del Metal/química , Modelos Químicos , Óxidos/química , Reproducibilidad de los Resultados , SemiconductoresRESUMEN
Piezoelectric cantilever beams are commonly utilized to harvest energy from environmental vibrations due to their simple structures. This paper optimizes a single crystal trapezoidal hollow structure piezoelectric cantilever beam vibration energy harvester with a copper substrate to achieve high energy density at a low frequency. Finite element analysis (FEA) is adopted to optimize the size of the copper substrate at first, and the piezoelectric energy harvester (PEH) is further optimized with a trapezoidal hollow structure under the optimal size of the copper substrate. The developed PEH with a trapezoidal hollow structure (La = 20 mm, Lb = 15 mm, and Lh = 40 mm), with a copper substrate of 80 mm × 33 mm × 0.2 mm, can obtain the best output performance. Under the condition of 1 g acceleration, the resonance frequency and peak voltage output were 23.29 Hz and 40.4 V, respectively. Compared with the unhollowed PEH, the developed trapezoidal hollow structure PEH can reduce its resonant frequency by 12.18% and increase output voltage by 34.67%, while also supplying a power density of 7.24 mW/cm3. This study verified the feasibility of the optimized design through simulation and experimental comparison.
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As the development of wireless communication devices tends to be highly integrated, the miniaturization of very low frequency (VLF) antenna units has always been an unresolved issue. Here, a novel VLF mechanical communication antenna using magnetoelectric (ME) laminates with bending-mode structure is realized. ME laminates combines magnetostrictive Metglas amorphous ribbons and piezoelectric 0.7Pb(Mg1/3Nb2/3)O3-0.3PbTiO3single crystal plates. From the simulation, we confirmed that the ME laminates can reduce the resonance peak from 18 kHz to 7.5 kHz by bending-mode structure. Experiment results show the resonance frequency can be farther reduced to 6.3 kHz by clamping one end of the ME antenna. The ME laminate exhibits a giant converse ME coefficient of 6 Oe cm V-1at 6.3 kHz. The magnetic flux density generated by the ME antenna has been tested along with distance ranging from 0 to 60 cm and it is estimated that a 1 fT flux could be detected around 100 m with an excitation power of 10 mW.
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BACKGROUND: The control of diseases related to atrial fibrillation (AF) may reduce the occurrence of AF, delay progression, and reduce complications, which is beneficial to the prevention and treatment of AF. An increasing number of studies have shown that AF is associated with depression. However, to date, there has not been a bibliometric analysis to examine this field systematically. Our study aimed to visualize the publications to determine the hotspots and frontiers in research on AF and depression and provide guidance and reference for further study. METHODS: Publications about AF and depression between 2001 and 2021 were retrieved from the Web of Science Core Collection (WOSCC) database. CiteSpace 5.8. R1, VOSviewer 1.6.16, and Excel 2019 software tools were used to conduct this bibliometric study. RESULTS: In total, 159 articles and reviews were analyzed. The number of publications has been increased sharply since 2018. David D. McManus had the largest number of publications. The most prolific country was the USA with 54 publications but the centrality was <0.1. The most prolific institution was Northeastern University. Three clusters were formed based on keywords: The first cluster was composed of atrial fibrillation, depression, anxiety, symptoms, ablation, and quality of life, et al. The second cluster were risk, prevalence, mortality, heart failure, association, et al. While the third cluster included anticoagulation, impact, stroke, management, warfarin, et al. After 2019, stroke and prediction are the keywords with strongest citation bursts. CONCLUSION: Research on AF and depression is in its infancy. Cooperation and exchanges between countries and institutions must be strengthened in the future. The effect of depression on prevalence and mortality in AF, depression on ablation in AF, and impact of depression on anticoagulation treatment in AF have been the focus of current research. Stroke prevention (including anticoagulant therapy) is the research frontier, which may still be the focus of research in the future.
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BACKGROUND: Hypoxia-induced pulmonary hypertension (HPH) is one of the fatal pathologies developed under hypobaric hypoxia and eventually leads to right ventricular (RV) remodeling and RV failure. Clinically, the mortality rate of RV failure caused by HPH is high and lacks effective drugs. Xinyang Tablet (XYT), a traditional Chinese medicine exhibits significant efficacy in the treatment of congestive heart failure and cardiac dysfunction. However, the effects of XYT on chronic hypoxia-induced RV failure are not clear. METHODS: The content of XYT was analyzed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS). Sprague-Dawley (SD) rats were housed in a hypobaric chamber (equal to the parameter in altitude 5500 m) for 21 days to obtain the RV remodeling model. Electrocardiogram (ECG) and hemodynamic parameters were measured by iWorx Acquisition & Analysis System. Pathological morphological changes in the RV and pulmonary vessels were observed by H&E staining and Masson's trichrome staining. Myocardial apoptosis was tested by TUNEL assay. Protein expression levels of TNF-α, IL-6, Bax, Bcl-2, and caspase-3 in the RV and H9c2 cells were detected by western blot. Meanwhile, H9c2 cells were induced by CoCl2 to establish a hypoxia injury model to verify the protective effect and mechanisms of XYT. A CCK-8 assay was performed to determine the viability of H9c2 cells. CoCl2-induced apoptosis was detected by Annexin-FITC/PI flow cytometry and Hoechst 33,258 staining. RESULTS: XYT remarkably improved RV hemodynamic disorder and ECG parameters. XYT attenuated hypoxia-induced pathological injury in RV and pulmonary vessels. We also observed that XYT treatment decreased the expression levels of TNF-α, IL-6, Bax/Bcl-2 ratio, and the numbers of myocardial apoptosis in RV. In H9c2 myocardial hypoxia model, XYT protected H9c2 cells against Cobalt chloride (CoCl2)-induced apoptosis. We also found that XYT could antagonize CoCl2-induced apoptosis through upregulating Bcl-2, inhibiting Bax and caspase-3 expression. CONCLUSIONS: We concluded that XYT improved hypoxia-induced RV remodeling and protected against cardiac injury by inhibiting apoptosis pathway in vivo and vitro models, which may be a promising therapeutic strategy for clinical management of hypoxia-induced cardiac injury.
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The nervous and immune systems are closely entwined to maintain the immune balance in health and disease. Here, we showed that LPS can activate suprarenal and celiac ganglia (SrG-CG) neurons and upregulate NPY expression in rats. Single-cell sequencing analysis revealed that knockdown of the NPY gene in SrG-CG altered the proliferation and activation of splenic lymphocytes. In a neuron and splenocyte coculture system and in vivo experiments, neuronal NPY in SrG-CG attenuated the splenic immune response. Notably, we demonstrated that neuronal NPF in Drosophila exerted a conservative immunomodulatory effect. Moreover, numerous SNPs in NPY and its receptors were significantly associated with human autoimmune diseases, which was further supported by the autoimmune disease patients and mouse model experiments. Together, we demonstrated that NPY is an ancient language for nervous-immune system crosstalk and might be utilized to alleviate inflammatory storms during infection and to modulate immune balance in autoimmune diseases.