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This study employed a precipitation method to synthesize zinc oxide@quaternised chitosan nanoparticles (ZnO@QAC NPs) containing different concentrations of zinc oxide, namely ZnO@QAC-2, ZnO@QAC-4, and ZnO@QAC-6. Subsequently, these nanoparticles were incorporated into matrices consisting of gelatine (Gn) and polyvinyl alcohol (PVA) separately, which were prepared by casting to form a biodegradable film. We assessed the physicochemical properties of ZnO@QAC NPs and physicochemical characteristics, antioxidant properties, antimicrobial activity and grape preservation efficacy of the film. Compared to the control group, the films showed a reduction in water vapor permeability by >9.38 %, an increase in tensile strength by over 51.95 %, over 70 % scavenging of ABTS free radicals, and good biocompatibility. Additionally, the antimicrobial activity of the films containing ZnO@QAC-6 increased by 37.6 %. In the grape preservation experiment, the weight loss of grapes wrapped in ZnO@QAC-2 film was reduced by 40.13 % on day 15 compared to unwrapped grapes. These results demonstrate that ZnO@QAC/PVA/Gn films have considerable potential for food packaging applications.
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Professor Svante Pääbo, Director of the Max Planck Institute for Evolutionary Anthropology, won the Nobel Prize in Physiology or Medicine in 2022 for his discoveries in ancient hominine genomes and human evolution. His pioneering work in sequencing and interpreting the paleo genomes of Neanderthals and Denisovans, as well as their relationship with the modern human genome, was groundbreaking in terms of our understanding of human origins. Nowadays, we can even use commercial kits to easily detect the proportion of Neanderthal genes in our own genomes. Recently, NSR conducted an interview with Professor Pääbo to learn about his interesting work chasing the ancient genomes and reconstructing human evolutionary and migration history from the DNA evidence, as well as his perspective on paleo genome studies and his advice to young researchers: follow your interests and be ready to try some crazy things.
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BACKGROUND: Abdominal perfusion pressure (APP) is a salient feature in the design of a prognostic model for patients with intra-abdominal hypertension (IAH). However, incomplete data significantly limits the size of the beneficiary patient population in clinical practice. Using advanced artificial intelligence methods, we developed a robust mortality prediction model with APP from incomplete data. METHODS: We retrospectively evaluated the patients with IAH from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Incomplete data were filled in using generative adversarial imputation nets (GAIN). Lastly, demographic, clinical, and laboratory findings were combined to build a 7-day mortality prediction model. RESULTS: We included 1354 patients in this study, of which 63 features were extracted. Data imputation with GAIN achieved the best performance. Patients with an APP< 60 mmHg had significantly higher all-cause mortality within 7 to 90 days. The difference remained significant in long-term survival even after propensity score matching (PSM) eliminated other mortality risks between groups. Lastly, the built machine learning model for 7-day modality prediction achieved the best results with an AUC of 0.80 in patients with confirmed IAH outperforming the other four traditional clinical scoring systems. CONCLUSIONS: APP reduction is an important survival predictor affecting the survival prognosis of patients with IAH. We constructed a robust model to predict the 7-day mortality probability of patients with IAH, which is superior to the commonly used clinical scoring systems.
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BACKGROUND: The challenges posed by an aging society are increasingly recognized, particularly regarding the potential impacts of high-fat diets and the trend toward younger ages of disease onset. The purpose of this study was to clarify the relationships between the prevalence of stroke in the general US population and PhenoAge (PA) and PhenoAgeAccel (PAA). METHODS: Key methods included a correlation heatmap to explore linear relationships between some of the variables and weighted multivariable logistic regression to assess associations between PA, PAA, and stroke. Restricted cubic spline (RCS) analysis was used to investigate nonlinear relationships and dose-response effects. The ability of the PAA to predict stroke risk was assessed by a nomogram model and a receiver operating characteristic curve. RESULTS: After adjusting for confounding variables, both continuous and categorical PA and PAA were significantly associated with stroke prevalence. RCS analysis revealed a significant nonlinear relationship between PA and stroke prevalence. Further subgroup RCS analysis indicated that maintaining PA below 31.6 could provide greater benefits across all races and genders, specifically for individuals aged 40-80 years and those who are overweight or obese. CONCLUSION: This study highlights the importance of stroke prevention in overweight and obese populations. Monitoring intermediary factors such as high-density lipoprotein cholesterol and waist circumference may reduce stroke risk. Additionally, PA and PAA may serve as novel markers for stroke, offering new directions for health management in an aging society.
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Artificial intelligence (AI) tools are changing the way we do science. AlphaFold basically solved the conundrum of protein structure prediction; DeepMD greatly improved the efficiency and accuracy of molecular simulations; and the emerging large language models such as ChatGPT are opening up more possibilities for scientific applications. In this panel, five experts from China and the US discussed the concept, development, bottlenecks and opportunities of AI for Science (AI4S), as well as their understanding of the relationship between AI and science. Roberto Car Professor at Department of Chemistry, Princeton University, USA Weinan E Professor at School of Mathematical Sciences, Peking University, China; AI for Science Institute, Beijing, China David Srolovitz Professor at Department of Mechanical Engineering, University of Hong Kong, China Han Wang Professor at the Institute of Applied Physics and Computational Mathematics, Chinese Academy of Sciences, China Linfeng Zhang (Chair) Chief scientific officer of DP Technology, China; AI for Science Institute, Beijing, China.
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Introduction. Pre-existing fluoroquinolones (FQs) resistance is a major threat in treating multidrug-resistant (MDR) tuberculosis. Sitafloxacin (Sfx) is a new broad-spectrum FQ.Hypothesis. Sfx is more active against drug-resistant Mycobacterium tuberculosis (Mtb) isolates.Aim. To determine whether there is cross-resistance between Sfx and ofloxacin (Ofx), levofloxacin (Lfx) and moxifloxacin (Mfx) in MDR Mtb.Methods. A total of 106 clinical Mtb isolates, including 23 pan-susceptible and 83 MDR strains, were analysed for Sfx, Lfx and Mfx resistance using MIC assay. The isolates were also subjected to whole-genome sequencing to analyse drug-resistant genes.Results. Sfx exhibited the most robust inhibition activity against Mtb clinical isolates, with a MIC50 of 0.0313 µg ml-1 and MIC90 of 0.125 µg ml-1, which was lower than that of Mfx (MIC50 = 0.0625 µg ml-1, MIC90 = 1 µg ml-1) and Lfx (MIC50 = 0.125 µg ml-1, MIC90 = 2 µg ml-1). We determined the tentative epidemiological cut-off values as 0.5 µg ml-1 for Sfx. Also, 8.43% (7/83), 43.37% (36/83), 42.17% (35/83) and 51.81% (43/83) MDR strains were resistant to Sfx, Mfx, Lfx and Ofx, respectively. Cross-resistance between Ofx, Lfx and Mfx was 80.43% (37/46). Only 15.22% (7/46) of the pre-existing FQs resistance isolates were resistant to Sfx. Among the 30 isolates with mutations in gyrA or gyrB, 5 (16.67%) were Sfx resistant. The combination of Sfx and rifampicin could exert partial synergistic effects, and no antagonism between Sfx and six clinically important anti-Mtb antibiotics was evident.Conclusion. Sfx exhibited superior activity against MDR isolates comparing to Lfx and Mfx, and could potentially overcome the majority pre-existing FQs resistance in Mtb strains.
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Antituberculosos , Farmacorresistencia Bacteriana Múltiple , Fluoroquinolonas , Levofloxacino , Pruebas de Sensibilidad Microbiana , Moxifloxacino , Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Fluoroquinolonas/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Moxifloxacino/farmacología , Levofloxacino/farmacología , Humanos , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Antituberculosos/farmacología , Secuenciación Completa del GenomaRESUMEN
OBJECTIVE: Post-stroke depression (PSD) is a common neurological and psychiatric sequelae following a stroke, often surpassing the primary effects of the stroke due to its strong correlation with high mortality rates. In recent years, non-pharmacological therapy has garnered significant attention as a supplementary treatment for PSD, becoming widely adopted in clinical practice. However, the efficacy of specific intervention strategies remains unclear. This study aimed to conduct a network meta-analysis (NMA) of published studies to compare the efficacy of different non-pharmacological therapies for treating PSD. METHOD: We systematically searched five databases from inception through March 2024 to identify randomized controlled trials (RCTs) evaluating non-pharmacological therapies for the treatment of PSD. We considered individual intervention and intervention class. Intervention classes included traditional Chinese medicine (TCM), non-invasive electrotherapy stimulation (NIES), psychotherapy (PT), exercise therapy, hyperbaric oxygen, and combined interventions. The NMA was conducted using R and Stata software, following a frequency-based methodology. Assessment of methodological quality and risk of bias was conducted using the Risk of Bias assessment tool 2.0. Therapies were ranked using the P-score, and box-plots visualization, meta-regression, and sensitivity analysis, were performed to assess transitivity, heterogeneity, and consistency, respectively. RESULTS: The NMA included 43 studies with a total of 3138 participants. Random-effects models revealed significant efficacy for acupuncture (ACUP) (P-score = 0.92; pooled standardized mean difference (95% CI): -3.12 (-4.63 to -1.60)) and transcranial direct current stimulation (P-score = 0.85; -2.78 (-5.06 to -0.49)) compared to the treatment as usual (TAU) group. In categorical comparisons, TCM_PT (P-score = 0.82; -1.91 (-3.54 to -0.28)), TCM (P-score = 0.79; -1.65 (-2.33 to -0.97)), and NIES (P-score = 0.74; -1.54 (-2.62 to -0.46)) showed significant differences compared to TAU group. Furthermore, our results indicated no significant difference between PT and the control groups. However, Confidence in Network Meta-Analysis results indicated very low overall evidence grade. CONCLUSION: Limited evidence suggests that ACUP may be the most effective non-pharmacological therapy for improving PSD, and TCM_PT is the best intervention class. However, the evidence quality is very low, underscoring the need for additional high-quality RCTs to validate these findings, particularly given the limited number of RCTs available for each therapy.
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Dr. Xiankang Dou () was appointed the President of the National Natural Science Foundation of China (NSFC) in April 2023. As a distinguished researcher specializing in studying the middle and upper atmosphere of earth, Dr. Dou had served as the President of Wuhan University during 2016 to 2022 and was elected an academician of the Chinese Academy of Sciences (CAS) in 2017. At his new post in NSFC, Dr. Dou's first priorities include curtailing personal favors in the review process (often known as 'say hello' with an intent to lobby), reforming the scoring and renewing mechanisms for the National Science Fund for Distinguished Young Scholars (DYS), opening the channel for DYS applications to researchers from Hong Kong and Macau, extending the age limit of female scientists for applying for DYS, and initiating funding programs for outstanding doctoral and undergraduate students. Recently, National Science Review (NSR) had an interview with Dr. Dou. He believes only through reform and experimentation can NSFC make steady progress in its efforts to support research of basic science and applied basic science in China and to cultivate promising scholars.
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BACKGROUND: Acute myocardial infarction (AMI) is one of the most severe cardiovascular diseases and is associated with a high risk of in-hospital mortality. However, the current deep learning models for in-hospital mortality prediction lack interpretability. OBJECTIVE: This study aims to establish an explainable deep learning model to provide individualized in-hospital mortality prediction and risk factor assessment for patients with AMI. METHODS: In this retrospective multicenter study, we used data for consecutive patients hospitalized with AMI from the Chongqing University Central Hospital between July 2016 and December 2022 and the Electronic Intensive Care Unit Collaborative Research Database. These patients were randomly divided into training (7668/10,955, 70%) and internal test (3287/10,955, 30%) data sets. In addition, data of patients with AMI from the Medical Information Mart for Intensive Care database were used for external validation. Deep learning models were used to predict in-hospital mortality in patients with AMI, and they were compared with linear and tree-based models. The Shapley Additive Explanations method was used to explain the model with the highest area under the receiver operating characteristic curve in both the internal test and external validation data sets to quantify and visualize the features that drive predictions. RESULTS: A total of 10,955 patients with AMI who were admitted to Chongqing University Central Hospital or included in the Electronic Intensive Care Unit Collaborative Research Database were randomly divided into a training data set of 7668 (70%) patients and an internal test data set of 3287 (30%) patients. A total of 9355 patients from the Medical Information Mart for Intensive Care database were included for independent external validation. In-hospital mortality occurred in 8.74% (670/7668), 8.73% (287/3287), and 9.12% (853/9355) of the patients in the training, internal test, and external validation cohorts, respectively. The Self-Attention and Intersample Attention Transformer model performed best in both the internal test data set and the external validation data set among the 9 prediction models, with the highest area under the receiver operating characteristic curve of 0.86 (95% CI 0.84-0.88) and 0.85 (95% CI 0.84-0.87), respectively. Older age, high heart rate, and low body temperature were the 3 most important predictors of increased mortality, according to the explanations of the Self-Attention and Intersample Attention Transformer model. CONCLUSIONS: The explainable deep learning model that we developed could provide estimates of mortality and visual contribution of the features to the prediction for a patient with AMI. The explanations suggested that older age, unstable vital signs, and metabolic disorders may increase the risk of mortality in patients with AMI.
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Aprendizaje Profundo , Mortalidad Hospitalaria , Infarto del Miocardio , Humanos , Infarto del Miocardio/mortalidad , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Algoritmos , Factores de Riesgo , Curva ROCRESUMEN
Trophoblast stem cells (TSCs) can be chemically converted from embryonic stem cells (ESCs) in vitro. Although several transcription factors (TFs) have been recognized as essential for TSC formation, it remains unclear how differentiation cues link elimination of stemness with the establishment of TSC identity. Here, we show that PRDM14, a critical pluripotent circuitry component, is reduced during the formation of TSCs. The reduction is further shown to be due to the activation of Wnt/ß-catenin signaling. The extinction of PRDM14 results in the erasure of H3K27me3 marks and chromatin opening in the gene loci of TSC TFs, including GATA3 and TFAP2C, which enables their expression and thus the initiation of the TSC formation process. Accordingly, PRDM14 reduction is proposed here as a critical event that couples elimination of stemness with the initiation of TSC formation. The present study provides novel insights into how induction signals initiate TSC formation.
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Diferenciación Celular , Proteínas de Unión al ADN , Factores de Transcripción , Trofoblastos , Vía de Señalización Wnt , Trofoblastos/metabolismo , Trofoblastos/citología , Animales , Ratones , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Diferenciación Celular/genética , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Factor de Transcripción GATA3/metabolismo , Factor de Transcripción GATA3/genética , Factor de Transcripción AP-2/metabolismo , Factor de Transcripción AP-2/genética , Células Madre/metabolismo , Células Madre/citología , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Histonas/metabolismo , Histonas/genéticaRESUMEN
Postmenopausal osteoporosis (PMOP) is a common kind of osteoporosis that is associated with excessive osteocyte death and bone loss. Previous studies have shown that TNF-α-induced osteocyte necroptosis might exert a stronger effect on PMOP than apoptosis, and TLR4 can also induce cell necroptosis, as confirmed by recent studies. However, little is known about the relationship between TNF-α-induced osteocyte necroptosis and TLR4. In the present study, we showed that TNF-α increased the expression of TLR4, which promoted osteocyte necroptosis in PMOP. In patients with PMOP, TLR4 was highly expressed at skeletal sites where exists osteocyte necroptosis, and high TLR4 expression is correlated with enhanced TNF-α expression. Osteocytes exhibited robust TLR4 expression upon exposure to necroptotic osteocytes in vivo and in vitro. Western blotting and immunofluorescence analyses demonstrated that TNF-α upregulated TLR4 expression in vitro, which might further promote osteocyte necroptosis. Furthermore, inhibition of TLR4 by TAK-242 in vitro effectively blocked osteocyte necroptosis induced by TNF-α. Collectively, these results suggest a novel TLR4-mediated process of osteocyte necroptosis, which might increase osteocyte death and bone loss in the process of PMOP.
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Osteocitos , Osteoporosis Posmenopáusica , Receptor Toll-Like 4 , Factor de Necrosis Tumoral alfa , Femenino , Humanos , Necroptosis , Osteocitos/metabolismo , Osteoporosis Posmenopáusica/metabolismo , Receptor Toll-Like 4/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Therapeutic cancer vaccines fail to produce satisfactory outcomes against solid tumors since vaccine-induced anti-tumor immunity is significantly hampered by immunosuppression. Generating an in situ cancer vaccine targeting immunological cold tumor microenvironment (TME) appears attractive. Here, a type of free-field based whole-body ultrasound (US)-driven nanovaccines are constructed, named G5-CHC-R, by conjugating the sonosensitizer, Chenghai chlorin (CHC) and the immunomodulator, resiquimod (R848) on top of a super small-sized dendrimeric nanoscaffold. Once entering tumors, R848 can be cleaved from a hypoxia-sensitive linker, thus modifying the TME via converting macrophage phenotypes. The animals bearing orthotopic pancreatic cancer with intestinal metastasis and breast cancer with lung metastasis are treated with G5-CHC-R under a free-field based whole-body US system. Benefit from the deep penetration capacity and highly spatiotemporal selectiveness, G5-CHC-R triggered by US represented a superior alternative for noninvasive irradiation of deep-seated tumors and magnification of local immune responses via driving mass release of tumor antigens and "cold-warm-hot" three-state transformation of TME. In addition to irradiating primary tumors, a robust adaptive anti-tumor immunity is potentiated, leading to successful induction of systemic tumor suppression. The sono-nanovaccines with good biocompatibility posed wide applicability to a broad spectrum of tumors, revealing immeasurable potential for translational research in oncology.
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Vacunas contra el Cáncer , Neoplasias , Animales , Nanovacunas , Ultrasonografía , Inmunidad Adaptativa , Adyuvantes Inmunológicos , Neoplasias/diagnóstico por imagen , Neoplasias/terapiaRESUMEN
BACKGROUND: Preeclampsia is a serious disease of pregnancy that lacks early diagnosis methods or effective treatment, except delivery. Dysregulated uterine immune cells and spiral arteries are implicated in preeclampsia, but the mechanistic link remains unclear. METHODS: Single-cell RNA sequencing and spatial transcriptomics were used to identify immune cell subsets associated with preeclampsia. Cell-based studies and animal models including conditional knockout mice and a new preeclampsia mouse model induced by recombinant mouse galectin-9 were applied to validate the pathogenic role of a CD11chigh subpopulation of decidual macrophages (dMφ) and to determine its underlying regulatory mechanisms in preeclampsia. A retrospective preeclampsia cohort study was performed to determine the value of circulating galectin-9 in predicting preeclampsia. RESULTS: We discovered a distinct CD11chigh dMφ subset that inhibits spiral artery remodeling in preeclampsia. The proinflammatory CD11chigh dMφ exhibits perivascular enrichment in the decidua from patients with preeclampsia. We also showed that trophoblast-derived galectin-9 activates CD11chigh dMφ by means of CD44 binding to suppress spiral artery remodeling. In 3 independent preeclampsia mouse models, placental and plasma galectin-9 levels were elevated. Galectin-9 administration in mice induces preeclampsia-like phenotypes with increased CD11chigh dMφ and defective spiral arteries, whereas galectin-9 blockade or macrophage-specific CD44 deletion prevents such phenotypes. In pregnant women, increased circulating galectin-9 levels in the first trimester and at 16 to 20 gestational weeks can predict subsequent preeclampsia onset. CONCLUSIONS: These findings highlight a key role of a distinct perivascular inflammatory CD11chigh dMφ subpopulation in the pathogenesis of preeclampsia. CD11chigh dMφ activated by increased galectin-9 from trophoblasts suppresses uterine spiral artery remodeling, contributing to preeclampsia. Increased circulating galectin-9 may be a biomarker for preeclampsia prediction and intervention.
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Decidua , Galectinas , Macrófagos , Preeclampsia , Remodelación Vascular , Preeclampsia/metabolismo , Preeclampsia/inmunología , Embarazo , Femenino , Animales , Galectinas/metabolismo , Macrófagos/metabolismo , Macrófagos/inmunología , Macrófagos/patología , Ratones , Humanos , Decidua/metabolismo , Decidua/patología , Ratones Noqueados , Útero/metabolismo , Útero/irrigación sanguínea , Modelos Animales de Enfermedad , Receptores de Hialuranos/metabolismo , Receptores de Hialuranos/genética , Estudios Retrospectivos , Ratones Endogámicos C57BL , Antígenos CD11RESUMEN
BACKGROUND: Investigating the underlying molecular mechanisms responsible for endometrial dysfunction in women with PCOS is essential, particularly focusing on the role of hyperinsulinemia. METHODS: We explored the role of insulin in the decidualization process using a synthetic decidualization assay. To dissect the effects of PI3K/AKT-NR4A signaling, we employed small interfering RNAs (siRNAs) targeting the NR4A genes and inhibitors of the PI3K/AKT pathway. We also investigated the disruption of AKT-NR4A1 signaling in the endometrium of PCOS female rats induced with dehydroepiandrosterone (DHEA). Quantitative real-time PCR (qRT-PCR) and Western blot (WB) analyses were utilized to evaluate gene expression regulation. RESULTS: Insulin was found to suppress the expression of decidualization markers in human endometrial stromal cells (hESC) in a dose-dependent manner, concurrently triggering an inappropriate activation of the PI3K/AKT pathway. Members of the NR4A family, as downstream effectors in the PI3K/AKT pathway, were implicated in the insulin-induced disruptions during the decidualization process. Moreover, the endometrium of PCOS models showed significantly elevated levels of phosphorylated (Ser473) AKT, with a corresponding reduction in Nr4a1 protein. CONCLUSIONS: Our research demonstrates that insulin negatively regulates decidualization in hESC via the PI3K/AKT-NR4A pathway. In vivo analysis revealed a significant dysregulation of the AKT-NR4A1 pathway in the endometrium of PCOS rats. These findings offer novel insights into the pathogenesis of infertility and endometrial disorders associated with hyperinsulinemia in PCOS.
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Hiperinsulinismo , Infertilidad , Síndrome del Ovario Poliquístico , Animales , Femenino , Humanos , Ratas , Endometrio/metabolismo , Hiperinsulinismo/metabolismo , Hiperinsulinismo/patología , Insulina/metabolismo , Miembro 1 del Grupo A de la Subfamilia 4 de Receptores Nucleares , Fosfatidilinositol 3-Quinasas/metabolismo , Síndrome del Ovario Poliquístico/patología , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
Here we report the Assessment Report on Invasive Alien Species and their Control released by IPBES, and the status of IAS in China.
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Tire wear particles (TWPs) have caused increasing concerns due to their detrimental effects on the soil ecosystem. However, the role of weathering in altering the toxicity of TWP to soil organisms is poorly understood. In this study, the toxicity of original and photoaged TWP was compared using earthworms (Eisenia fetida) as soil model organisms. The obtained results indicated that photoaging of TWP resulted in an increase of environmentally persistent free radicals (EPFRs) from 3.69 × 1017 to 5.20 × 1017 spin/g. Meanwhile, photoaged TWP induced the changes of toxic endpoint in E. fetide, i.e., the increase of the weight loss and death ratio from 0.0425 to 0.0756 g/worm and 23.3 to 50% compared to original TWP under a 10% concentration, respectively. Analyses of transcriptomics, antioxidant enzyme activity, and histopathology demonstrated that the enhanced toxicity was mainly due to oxidative damage, which was induced by disruption in the antioxidant defense system. Free-radical quenching and correlation analysis further suggested that the excessive production of ex vivo reactive oxygen species, induced by EPFRs, led to the exhaustion of the antioxidant defense system. Overall, this work provides new insights into the potential hazard of the weathered TWP in a soil environment and has significant implications for the recycling and proper disposal of spent tire particles.
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Oligoquetos , Contaminantes del Suelo , Animales , Antioxidantes/farmacología , Ecosistema , Contaminantes del Suelo/toxicidad , Estrés Oxidativo , Especies Reactivas de Oxígeno/farmacología , SueloRESUMEN
OBJECTIVE: To investigate the effect of interferon-γ (IFN-γ) on the immune microenvironment and the polarity of tumor-associated macrophages (TAMs) in stage IA non-small cell lung cancer (NSCLC) and its mechanisms. METHODS: Human non-small cell lung cancer A549 cells were treated with a series of IFN-γ concentrations (0, 50, 100, 150, 200, 250, and 300 ng/mL). Tumor tissues from patients with stage IA NSCLC were cultured using the air-liquid interface culture technique to establish a tumor microenvironment (TME) organ model. The NSCLC model was constructed by subcutaneously embedding small tumor pieces into the back of nonobese diabetic severe combined immune deficiency (NOD SCID) mice. The size and weight of the tumors were recorded, and the tumor volume was calculated. CCK-8 assays were used to investigate cell proliferation, flow cytometry and TUNEL staining were used to evaluate cell apoptosis, colony formation was investigated by cloning experiments, and cell invasion and migration were evaluated by Transwell assays and scratch tests. The expression of apoptosis-related proteins (Bax, Bcl-2 and C-caspase 3), M2 polarization-related markers (CD163, CD206 and IDO1), and marker proteins of cytotoxic T cells and helper T cells (CD8 and CD4) was detected by Western blot. The expression of Ki-67 and IDO1 was detected by immunohistochemistry, and the levels of IL-6, IL-10, IL-13 and TNF-α were measured by ELISA. The expression of CD68 was measured by RTâqPCR, and the phagocytosis of TAMs was evaluated by a Cell Trace CFSE kit and cell probe staining. RESULTS: The proliferation activity of A549 cells increased with increasing IFN-γ concentration and peaked when the concentration reached 200 ng/mL, and the proliferation activity of A549 cells was suppressed thereafter. After treatment with 200 ng/mL IFN-γ, the apoptosis rate of cells decreased, the number of cell colonies increased, the invasion and migration of cells were promoted, the expression of Bax and C-caspase 3 was downregulated, and the expression of Bcl-2 was upregulated in cells and the TME model. In the TME model, CD163, CD206, IDO1 and Ki-67 were upregulated, CD8 and CD4 were downregulated, apoptosis was reduced, the levels of IL-6 and TNF-α were decreased, and the levels of IL-10 and IL-13 were increased. IL-4 induced TAMs to express CD163 and CD206, reduced the levels of IL-6 and TNF-α, increased the levels of IL-10 and IL-13, and weakened the phagocytic function of TAMs. IFN-γ treatment further enhanced the effect of IL-4 and enhanced the viability of A549 cells. IDO1 decreased the viability of T cells and NK cells, while suppressing the effect of IFN-γ. In mice, compared with NSCLC mice, the tumor volume and weight of the IFN-γ group were increased, the expression of CD163, CD206, IDO1, Ki-67 and Bcl-2 in tumor tissue was upregulated, the expression of Bax and C-caspase 3 was downregulated, and apoptosis was reduced. The levels of IL-6 and TNF-α were decreased, and the levels of IL-10 and IL-13 were increased in the serum of mice. CONCLUSION: In stage IA NSCLC, a low concentration of IFN-γ promotes the polarization of TAMs to the M2 phenotype in the TME model by upregulating the expression of IDO1, promoting the viability of cancer cells, inhibiting the viability of T cells and NK cells, and thus establishing an immune microenvironment conducive to tumor progression.
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Carcinoma de Pulmón de Células no Pequeñas , Interferón gamma , Neoplasias Pulmonares , Microambiente Tumoral , Animales , Humanos , Ratones , Proteína X Asociada a bcl-2 , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Caspasa 3 , Interferón gamma/farmacología , Interleucina-10 , Interleucina-13 , Interleucina-4 , Interleucina-6 , Antígeno Ki-67 , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/metabolismo , Ratones SCID , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunología , Factor de Necrosis Tumoral alfaRESUMEN
Non-coding RNA (ncRNA) has been a very active research area over the past 30 years. From small ncRNA - the discovery of RNA interference won the lead researchers the Nobel Prize, to long ncRNA (lncRNA), which has attracted much attention in recent years, various ncRNAs participate in all kinds of biological processes and show a variety of biomedical application prospects. Recently, National Science Review (NSR) interviewed Ling-Ling Chen, a professor at the Center for Excellence in Molecular Cell Science (CEMCS) of the Chinese Academy of Sciences (CAS), deputy director of the State Key Laboratory of Molecular Biology and director of the CAS Key Laboratory of RNA Science and Engineering, to talk about the magic world of RNA. Ling-Ling Chen and her team have been studying ncRNA for more than 10 years, and have witnessed and promoted the development of this field. They discovered unconventional lncRNAs without polyadenylated (polyA) tails or N7-methylguanosine (m7G) caps, including sno-lncRNAs (small nucleolar lncRNAs), SPAs (5' snoRNA capped and 3' polyadenylated RNAs) and circRNAs (circular RNAs), and have made remarkable progress clarifying the biogenetic mechanisms and functions of these RNAs and exploring their biomedical application. Chen said: 'I am 45 years old. I hope I will not stagnate here, but make new discoveries.'
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Endogenous signals, namely nitric oxide (NO) and electrons, play a crucial role in regulating cell fate as well as the vascular and neuronal systems. Unfortunately, utilizing NO and electrical stimulation in clinical settings can be challenging due to NO's short half-life and the invasive electrodes required for electrical stimulation. Additionally, there is a lack of tools to spatiotemporally control gas release and electrical stimulation. To address these issues, an "electromagnetic messenger" approach that employs on-demand high-frequency magnetic field (HFMF) to trigger NO release and electrical stimulation for restoring brain function in cases of traumatic brain injury is introduced. The system comprises a NO donor (poly(S-nitrosoglutathione), pGSNO)-conjugated on a gold yarn-dynamos (GY) and embedded in an implantable silk in a microneedle. When subjected to HFMF, conductive GY induces eddy currents that stimulate the release of NO from pGSNO. This process significantly enhances neural stem cell (NSC) synapses' differentiation and growth. The combined strategy of using NO and electrical stimulation to inhibit inflammation, angiogenesis, and neuronal interrogation in traumatic brain injury is demonstrated in vivo.
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Lesiones Traumáticas del Encéfalo , Células-Madre Neurales , Humanos , Óxido Nítrico , Oro , Neuronas/fisiología , Lesiones Traumáticas del Encéfalo/terapiaRESUMEN
Chemistry is a basis for almost all science and engineering disciplines, and needs to be well mastered by both researchers and students. But in the eyes of many Chinese students and their parents, chemistry is not an initial choice because first, it seems to be less important than mathematics and physics, and second, chemistry-majored students usually cannot get high salaries after graduation, and may encounter safety risks when conducting chemical experiments. How can we encourage students in learning chemistry? How can we improve higher chemistry education so that students can truly grasp the basic chemical principles, increase their chemical skills and apply the learnt knowledge in their future careers? Here in this panel discussion, six experts in higher chemistry education try to give their observations and opinions on these issues. Yadong Li President at Anhui Normal University; inorganic chemist. Yan Li Professor at College of Chemistry and Molecular Engineering, Peking University. Jian Pei Professor at College of Chemistry and Molecular Engineering, Peking University. Zhenfeng Xi Professor at College of Chemistry and Molecular Engineering, Peking University. Song Gao (Chair) President at Sun Yat-sen University; inorganic chemist. Lan-Sun Zheng (Chair) Professor at College of Chemistry and Chemical Engineering, Xiamen University.