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Yeasts are pivotal brewing microbes that are associated with the flavor and quality of Chinese baijiu, yet research on dominant yeasts in strong-flavor baijiu brewing remains limited. In this study, Saccharomyces cerevisiae, Pichia kudriavzevii, and Kazachstania bulderi were identified as predominated yeasts in strong-flavor baijiu. Each strain showed distinct characteristics in ethanol resistance, thermal tolerance, and lactic acid tolerance, severally. S. cerevisiae FJ1-2 excelled in ethanol and ethyl ester production, P. kudriavzevii FJ1-1 in ethyl acetate, and K. bulderi FJ1-3 in lactic acid generation. Subsequently, the reinforced Fuqu of each yeast were severally prepared for application in baijiu brewing to verify their functions. Results revealed that the relative abundance of fortified yeast in each group rose. Pichia, Kazachstania, and Saccharomyces emerged as the core microbe for each group, respectively, by co-occurrence network analysis, influencing the microbiota to regulate flavor substances. In short, P. kudriavzevii FJ1-1 enhanced ethyl acetate. K. bulderi FJ1-3 improved ethyl caproate production and decreased levels of ethyl acetate and higher alcohols by modulating yeast community between Pichia and Saccharomyces. This is a systematic endeavor to study the functions of yeasts of strong-flavor baijiu, providing a solid basis for improving baijiu quality.
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PURPOSE: The aim of this study was to observe the influence of differential nutritional status on bone age (BA) change according to body mass index (BMI) and analyze the risk of advanced bone age in children with overweight and obesity. METHODS: In total 23,305 children from Beijing were included in this cross-sectional study. Childhood overweight and obesity were defined according to the China and World Health Organization growth criteria. The data were analyzed by the R coding platform version 4.3.0. RESULTS: Under the Chinese criteria, 29%, 15%, and 4% of boys with overweight; 33%, 33%, and 3% of boys with obesity; 39%, 25%, and 2% of girls with overweight; and 37%, 42% and 1% of girls with obesity had advanced, significantly advanced and delayed BA, respectively. After adjustment, overweight (odds ratio, 95% confidence interval, P under the Chinese criteria: 2.52, 2.30-2.75, <0.001 and 4.54, 4.06-5.09, <0.001) and obesity (4.31, 3.85-4.82, <0.001 and 14.01, 12.39-15.85, <0.001) were risk factors for both advanced BA and significantly advanced BA. CONCLUSIONS: Different nutritional statuses lead to differences in children's BA development. Children with overweight and obesity have higher rates of advanced BA under two growth criteria, and girls have more advances in BA than boys do. Overweight and obesity are risk factors for advanced BA.
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Glioblastoma (GBM) presents significant challenges due to its invasive nature and genetic heterogeneity. In this study, we investigated the impact of Small VCP/P97-Interacting Protein (SVIP) on GBM progression. Our results revealed elevated expression of Insulin-like Growth Factor Binding Protein 2 (IGFBP-2) and STIP1 homology and U-box containing protein 1 (STUB1), coupled with reduced SVIP levels in GBM samples. Notably, high IGFBP-2 expression correlated with poor prognosis. Mechanistically, SVIP competitively inhibited STUB1, selectively binding to VCP/p97, thereby reducing PTEN degradation. This SVIP-mediated regulation exerted influence on the PTEN/PI3K/AKT/mTOR pathway, leading to the suppression of GBM progression. Co-localization experiments demonstrated that SVIP hindered PTEN ubiquitination and degradation by outcompeting STUB1 for VCP/p97 binding. Moreover, SVIP overexpression resulted in reduced activation of AKT/mTOR signaling and facilitated autophagy. In vivo experiments using a GBM xenograft model substantiated the tumor-suppressive effects of SVIP, evident by suppressed tumor growth, decreased IGFBP-2 expression, and improved survival rates. Collectively, our findings underscore the functional significance of SVIP in GBM progression. By inhibiting STUB1 and stabilizing PTEN, SVIP modulates the expression of IGFBP-2 and attenuates the activation of the PI3K/AKT/mTOR pathway, thereby emerging as a promising therapeutic target for GBM treatment.
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Brain metastases (BMs) and high-grade gliomas (HGGs) are the most common and aggressive types of malignant brain tumors in adults, with often poor prognosis and short survival. As their clinical symptoms and image appearances on conventional magnetic resonance imaging (MRI) can be astonishingly similar, their accurate differentiation based solely on clinical and radiological information can be very challenging, particularly for "cancer of unknown primary", where no systemic malignancy is known or found. Non-invasive multiparametric MRI and radiomics offer the potential to identify these distinct biological properties, aiding in the characterization and differentiation of HGGs and BMs. However, there is a scarcity of publicly available multi-origin brain tumor imaging data for tumor characterization. In this paper, we introduce a multi-center, multi-origin brain tumor MRI (MOTUM) imaging dataset obtained from 67 patients: 29 with high-grade gliomas, 20 with lung metastases, 10 with breast metastases, 2 with gastric metastasis, 4 with ovarian metastasis, and 2 with melanoma metastasis. This dataset includes anonymized DICOM files alongside processed FLAIR, T1-weighted, contrast-enhanced T1-weighted, T2-weighted sequences images, segmentation masks of two tumor regions, and clinical data. Our data-sharing initiative is to support the benchmarking of automated tumor segmentation, multi-modal machine learning, and disease differentiation of multi-origin brain tumors in a multi-center setting.
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Neoplasias Encefálicas , Glioma , Imagen por Resonancia Magnética , Humanos , Neoplasias Encefálicas/diagnóstico por imagen , Glioma/diagnóstico por imagen , Glioma/patología , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Neoplasias Ováricas/diagnóstico por imagen , Neoplasias Ováricas/patología , Melanoma/diagnóstico por imagen , Melanoma/patologíaRESUMEN
BACKGROUND: In assessing the clinical utility and safety of 3.0 T intraoperative magnetic resonance imaging (iMRI) combined with multimodality functional MRI (fMRI) guidance in the resection of functional area gliomas, we conducted a study. METHOD: Among 120 patients with newly diagnosed functional area gliomas who underwent surgical treatment, 60 were included in each group: the integrated group with iMRI and fMRI and the conventional navigation group. Between-group comparisons were made for the extent of resection (EOR), preoperative and postoperative activities of daily living based on the Karnofsky performance status, surgery duration, and postoperative intracranial infection rate. RESULTS: Compared to the conventional navigation group, the integrated navigation group with iMRI and fMRI exhibited significant improvements in tumor resection (complete resection rate: 85.0% vs. 60.0%, P = 0.006) and postoperative life self-care ability scores (Karnofsky score) (median ± interquartile range: 90 ± 25 vs. 80 ± 30, P = 0.013). Additionally, although the integrated navigation group with iMRI and fMRI required significantly longer surgeries than the conventional navigation group (mean ± standard deviation: 411.42 ± 126.4 min vs. 295.97 ± 96.48 min, P<0.0001), there was no significant between-group difference in the overall incidence of postoperative intracranial infection (16.7% vs. 18.3%, P = 0.624). CONCLUSION: The combination of 3.0 T iMRI with multimodal fMRI guidance enables effective tumor resection with minimal neurological damage.
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Neoplasias Encefálicas , Glioma , Imagen por Resonancia Magnética , Humanos , Masculino , Femenino , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/diagnóstico por imagen , Glioma/cirugía , Glioma/diagnóstico por imagen , Persona de Mediana Edad , Imagen por Resonancia Magnética/métodos , Adulto , Anciano , Estudios Retrospectivos , Cirugía Asistida por Computador/métodos , Neuronavegación/métodos , Resultado del Tratamiento , Monitoreo Intraoperatorio/métodos , Procedimientos Neuroquirúrgicos/métodosRESUMEN
The levels-of-processing (LOP) framework, proposing that deep processing yields superior retention, has provided an important paradigm for memory research and a practical means of improving learning. However, the available levels-of-processing literature focuses on immediate memory performance. It is assumed within the LOP framework that deep processing will lead to slower forgetting than will shallow processing. However, it is unclear whether, or how, the initial level of processing affects the forgetting slopes over longer retention intervals. The present three experiments were designed to explore whether items encoded at qualitatively different LOP are forgotten at different rates. In the first two experiments, depth of processing was manipulated within-participants at encoding under deep and shallow conditions (semantic vs. rhyme judgement in Experiment 1; semantic vs. consonant-vowel pattern decision in Experiment 2). Recognition accuracy (d prime) was measured between-participants immediately after learning and at 30-min, 2-h, and 24-h delays. The third experiment employed a between-participants design, contrasting the rates of forgetting following semantic and phonological (rhyme) processing at immediate, 30-min, 2-h, and 6-h delays. Results from the three experiments consistently demonstrated a large effect size of levels of processing on immediate performance and a medium-to-large level effect size on delayed recognition, but crucially no LOP × delay group interaction. Analysis of the retention curves revealed no significant differences between the slopes of forgetting for deep and shallow processing. These results suggest that the rates of forgetting are independent of the qualitatively distinct encoding operations manipulated by levels of processing.
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Background: Policy makers and researchers are tasked with exploring ways to strengthen primary health care (PHC) to address the growing burden of non-communicable diseases (NCDs). This study aims to use a co-design approach (i.e., meaningful involvement of research end users in study planning and design) to develop PHC interventions to improve the management of hypertension and type 2 diabetes (T2DM) in four study sites in China. Methods: The study adopted a three-step co-design approach, including (1) a two-round Delphi panel with health system and NCD professionals to identify prioritised health system challenges, (2) three co-design workshops (in each study site) with local health administrators, PHC providers, and residents with hypertension and/or T2DM, respectively, to develop interventions and identify factors influencing implementation, and (3) another round of co-design workshops with local health administrators to summarise findings and reach consensus. Qualitative synthesis was conducted to analyse results from the workshops. Findings: Thirteen experts were involved in the two-round Delphi panel, which identified three prioritised health system challenges, including limited capacities of PHC providers, suboptimal service quality and evaluation mechanisms, and unreliable health information systems. The co-design workshops involved 116 local stakeholders in 16 sessions (four in each site), and developed three groups of interventions to address the challenges: (1) empowering PHC providers through on-the-job training for capacity building; (2) empowering patient communities through health education on healthy lifestyles and NCD self-management; and (3) empowering health administrators through local health data monitoring and strengthening governance for local PHC programs. Site-specific interventions were also considered to cater for different local contexts. Several recommendations were further identified for the implementation of these interventions, emphasising the importance of local customisation, community participation, and cross-sectoral collaborations. Interpretation: By engaging multiple stakeholders in priority setting and solution generation, this study summarised several key areas for change in health workforce, service delivery, and health information. Future research should examine the effectiveness and implementation of these interventions to improve NCD management in PHC in China. Funding: This study is funded by National Health and Medical Research Council (NHMRC) Global Alliance for Chronic Diseases funding (APP1169757) and National Natural Science Foundation of China (72074065). Shangzhi Xiong is supported by University of New South Wales tuition fee scholarship.
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OBJECTIVES: Health technology assessment (HTA) is increasingly crucial in medicine price negotiations in China, yet previous appraisals revealed national discrepancies on key economic evaluation issues: willingness-to-pay threshold, pricing models for multi-indication medicines, and comparator selection principles. This study aimed to collect expert opinions on these issues for future HTA evaluations. METHODS: A nationwide anonymous web-based survey encompassing experts across academia, HTA, consultancy/contract research organization/industry, service provider, and payer. In 2023, a generic invitation containing a web link to the questionnaire was disseminated via WeChat using convenience and snowball sampling. Agreement rates for questionnaire views were analyzed using descriptive statistics. The relationship between participants' responses and demographics was examined using appropriate logistic models. RESULTS: A total of 303 responses were received from experts in 34 cities. Key expert views include a suggested base willingness-to-pay threshold ranging from 0.5 to 1.5 times gross domestic product (52.1% agreement); elevated thresholds for childhood diseases, rare diseases, end-of-life diseases, and first-in-class medicines (>78.0% agreement); a single pricing model for multi-indication medicines (60.4% agreement); consideration of multiple medicines as comparators (79.9% agreement); and avoiding the use of centrally procured medicines as comparators for medicines with a time to market of less than 3 years (71.0% agreement). Participants who are service provider had lower odds of selecting higher thresholds (odds ratio 0.26; P < .01) than responders from consultancy/contract research organization/industry. CONCLUSIONS: Expert views indicate the need for substantial changes in China's current HTA methods, highlighting the need for increased investment in HTA processes and expertise cultivation.
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Glioma is the most common malignant tumor of the central nervous system, with EZH2 playing a crucial regulatory role. This study further explores the abnormal expression of EZH2 and its mechanisms in regulating glioma progression. Additionally, it was found that IHMT-337 can potentially be a therapeutic agent for glioma. The prognosis, expression, and localization of EZH2 were determined using bioinformatics, IHC staining, Western blot (WB) analysis, and immunofluorescence (IF) localization. The effects of EZH2 on cell function were assessed using CCK-8 assays, Transwell assays, and wound healing assays. Public databases and RT-qPCR were utilized to identify downstream targets. The mechanisms regulating these downstream targets were elucidated using MS-PCR and WB analysis. The efficacy of IHMT-337 was demonstrated through IC50 measurements, WB analysis, and RT-qPCR. The effects of IHMT-337 on glioma cells in vitro were evaluated using Transwell assays, EdU incorporation assays, and flow cytometry. The potential of IHMT-337 as a treatment for glioma was assessed using a blood-brain barrier (BBB) model and an orthotopic glioma model. Our research confirms significantly elevated EZH2 expression in gliomas, correlating with patient prognosis. EZH2 facilitates glioma proliferation, migration, and invasion alongside promoting SLC12A5 DNA methylation. By regulating SLC12A5 expression, EZH2 activates the WNK1-OSR1-NKCC1 pathway, enhancing its interaction with ERM to promote glioma migration. IHMT-337 targets EZH2 in vitro to inhibit WNK1 activation, thereby suppressing glioma cell migration. Additionally, it inhibits cell proliferation and arrests the cell cycle. IHMT-337 has the potential to cross the BBB and has successfully inhibited glioma progression in vivo. This study expands our understanding of the EZH2-SLC12A5 axis in gliomas, laying a new foundation for the clinical translation of IHMT-337 and offering new insights for precision glioma therapy.
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Proliferación Celular , Proteína Potenciadora del Homólogo Zeste 2 , Glioma , Glioma/metabolismo , Glioma/genética , Glioma/patología , Glioma/tratamiento farmacológico , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Proteína Potenciadora del Homólogo Zeste 2/genética , Humanos , Animales , Línea Celular Tumoral , Ratones , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Regulación Neoplásica de la Expresión Génica , Movimiento Celular , Transducción de Señal , Ensayos Antitumor por Modelo de Xenoinjerto , PronósticoRESUMEN
BACKGROUND: Early detection of patients at risk of falling is crucial. This study was designed to develop and internally validate a novel risk score to classify patients at risk of falls. METHODS: A total of 334 older people from a fall clinic in a medical center were selected. Least absolute shrinkage and selection operator (LASSO) regression was used to minimize the potential concatenation of variables measured from the same patient and the overfitting of variables. A logistic regression model for 1-year fall prediction was developed for the entire dataset using newly identified relevant variables. Model performance was evaluated using the bootstrap method, which included measures of overall predictive performance, discrimination, and calibration. To streamline the assessment process, a scoring system for predicting 1-year fall risk was created. RESULTS: We developed a new model for predicting 1-year falls, which included the FRQ-Q1, FRQ-Q3, and single-leg standing time (left foot). After internal validation, the model showed good discrimination (C statistic, 0.803 [95% CI 0.749-0.857]) and overall accuracy (Brier score, 0.146). Compared to another model that used the total FRQ score instead, the new model showed better continuous net reclassification improvement (NRI) [0.468 (0.314-0.622), P < 0.01], categorical NRI [0.507 (0.291-0.724), P < 0.01; cutoff: 0.200-0.800], and integrated discrimination [0.205 (0.147-0.262), P < 0.01]. The variables in the new model were subsequently incorporated into a risk score. The discriminatory ability of the scoring system was similar (C statistic, 0.809; 95% CI, 0.756-0.861; optimism-corrected C statistic, 0.808) to that of the logistic regression model at internal bootstrap validation. CONCLUSIONS: This study resulted in the development and internal verification of a scoring system to classify 334 patients at risk for falls. The newly developed score demonstrated greater accuracy in predicting falls in elderly people than did the Timed Up and Go test and the 30-Second Chair Sit-Stand test. Additionally, the scale demonstrated superior clinical validity for identifying fall risk.
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Accidentes por Caídas , Vida Independiente , Humanos , Accidentes por Caídas/prevención & control , Femenino , Masculino , Anciano , Anciano de 80 o más Años , Medición de Riesgo/métodos , Evaluación Geriátrica/métodos , Valor Predictivo de las Pruebas , Factores de RiesgoRESUMEN
Background: Boron neutron capture therapy (BNCT) stands out as a propitious anti-cancer modality. 18F-boronophenylalanine positron emission tomography (BPA-PET) holds the potential to ascertain the concentration of BPA within the tumor, enabling meticulous treatment planning and outcome evaluation. However, no studies have been conducted on comparing the outcomes of those treated with BNCT to those who did not undergo this therapy. This study endeavors to analyze the correlation between BPA-PET and BNCT in the context of malignant brain tumors, and assess the survival outcomes following BNCT. Methods: A cohort study was performed on patients who underwent BPA-PET between February 2017 and April 2022 in our hospital. Patients were stratified into two groups: those subjected to BNCT (Group 1) and those not (Group 2). The tumor to normal tissue (T/N) ratio derived from BPA-PET was set at 2.5. The findings were scrutinized based on clinical follow-up. Student's t-test and Chi-squared test were employed to discern differences between the groups. A cumulative survival curve was constructed employing the Kaplan-Meier method. Differences were considered statistically significant at P<0.05. Results: In total, 116 patients with T/N ratios obtained from BPA-PET were enrolled. BNCT was administered to 58 patients, while mortality was observed in 100 patients. The median overall survival (OS) for the two groups was 8.5 and 6.0 months, respectively. The cumulative OS exhibited no significant discrepancy between the two groups, nor in their T/N ratios. Within Group 1, 44 out of 58 (75.9%) patients exhibited T/N ratios exceeding 2.5. Excluding 3 patients who expired within 3 months, 55 out of 58 patients were evaluated for response after BNCT. The objective response rate (ORR) was 30.9%. Patients achieving ORR displayed substantially higher survival rates compared to those without (median OS 13.5 vs. 8.3 months, P=0.0021), particularly when T/N ratio exceeded 2.5 (median OS 14.8 vs. 9.0 months, P=0.0199). Conclusions: BNCT does not appear indispensable for prolonging the survival of patients afflicted with malignant brain tumors. Nevertheless, it proves advantageous when ORR is attained, a condition closely linked to the values of T/N ratio derived from BPA-PET.
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BACKGROUND: Radium-223 dichloride (Ra-223) prolongs overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) with symptomatic bone metastases. However, there is considerable variation in outcomes among individuals. We aimed to evaluate the prognostic determinants associated with patient survival following National Health Insurance (NHI) reimbursement for Ra-223 therapy in Taiwan. METHODS: Patients with mCRPC who underwent Ra-223 treatment at Taipei Veterans General Hospital were retrospectively enrolled. Each intravenous Ra-223 dose was administered at 55 kBq/kg at 4-week intervals. Clinical outcomes were obtained from medical records; potential prognostic factors for survival were assessed. Kaplan-Meier analysis was used to generate cumulative survival curves; between-group differences were evaluated using the Chi-squared test. Statistical significance was set at p < 0.05. RESULTS: Seventy-six patients underwent Ra-223 therapy; 62 patients received NHI reimbursement and the remainder self-paid. Fifty patients (65.8%) completed six cycles of treatment; 26 (34.2%) received 1 to 5 cycles. Mortality occurred in 47 patients. Factors significantly associated with survival included ≤five bone metastases ( p = 0.0018), baseline prostate-specific antigen (PSA) ≤36 ng/mL ( p = 0.0004), baseline alkaline phosphate (ALP) <115 U/L ( p = 0.0007), and baseline hemoglobin (Hb) >12 g/dL ( p = 0.0029). Patients who completed six cycles of treatment achieved significantly higher OS compared to those who did not ( p < 0.0001). There has been a 4.4-fold increase in the number of patients since reimbursement began; there was no significant difference in OS between patients who received NHI reimbursement and those who self-paid. CONCLUSION: Administration of Ra-223 demonstrates considerable potential to extend the survival of patients with mCRPC. Survival outcomes may be influenced by various prognostic factors. However, no significant difference in OS was observed subsequent to reimbursement of Ra-223 therapy for mCRPC through the NHI system in Taiwan.
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Programas Nacionales de Salud , Neoplasias de la Próstata Resistentes a la Castración , Radio (Elemento) , Humanos , Masculino , Radio (Elemento)/uso terapéutico , Anciano , Neoplasias de la Próstata Resistentes a la Castración/radioterapia , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Neoplasias de la Próstata Resistentes a la Castración/patología , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Estudios Retrospectivos , Persona de Mediana Edad , Anciano de 80 o más Años , Taiwán , Neoplasias Óseas/secundario , Neoplasias Óseas/radioterapia , Neoplasias Óseas/mortalidad , Radioisótopos/uso terapéuticoRESUMEN
The extracellular superoxide dismutases (ecSODs) secreted by Microplitis bicoloratus reduce the reactive oxygen species (ROS) stimulated by the Microplitis bicoloratus bracovirus. Here, we demonstrate that the bacterial transferase hexapeptide (hexapep) motif and bacterial-immunoglobulin-like (BIg-like) domain of ecSODs bind to the cell membrane and transiently open hemichannels, facilitating ROS reductions. RNAi-mediated ecSOD silencing in vivo elevated ROS in host hemocytes, impairing parasitoid larva development. In vitro, the ecSOD-monopolymer needed to be membrane bound to open hemichannels. Furthermore, the hexapep motif in the beta-sandwich of ecSOD49 and ecSOD58, and BIg-like domain in the signal peptides of ecSOD67 were required for cell membrane binding. Hexapep motif and BIg-like domain deletions induced ecSODs loss of adhesion and ROS reduction failure. The hexapep motif and BIg-like domain mediated ecSOD binding via upregulating innexins and stabilizing the opened hemichannels. Our findings reveal a mechanism through which ecSOD reduces ROS, which may aid in developing anti-redox therapy.
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BACKGROUND: Chickens are one of the most widely farmed animals worldwide and play a crucial role in meat and egg production. Gut microbiota is essential for chickens' health, disease, growth, and egg production. However, native chickens such as Jianghan chickens have better meat and egg production quality than centralized chickens, their intestinal microbial diversity is richer, and the potential gut microbial resources may bring health benefits to the host. RESULTS: The bacterial species composition in the gut microbiota of Jianghan chickens is similar to that of other chicken breeds, with Phocaeicola and Bacteroides being the most abundant bacterial genera. The LEfSe analysis revealed significant differences in species composition and functional profiles between samples from Jingzhou and the other three groups. Functional annotation indicated that the gut microbiota of Jianghan chickens were dominated by metabolic genes, with the highest number of genes related to carbohydrate metabolism. Several antibiotic resistance genes (ARGs) were found, and the composition of ARGs was similar to that of factory-farmed chickens, suggesting that antibiotics were widely present in the gut microbiota of Jianghan chickens. The resistance genes of Jianghan chickens are mainly carried by microorganisms of the Bacteroidota and Bacillota phylum. In addition, more than 829 isolates were selected from the microbiota of Jianghan chickens. Following three rounds of acid and bile tolerance experiments performed on all the isolated strains, it was determined that six strains of Pediococcus acidilactici exhibited consistent tolerance. Further experiments confirmed that three of these strains (A4, B9, and C2) held substantial probiotic potential, with P. acidilactici B9 displaying the highest probiotic potential. CONCLUSIONS: This study elucidates the composition of the intestinal microbiota and functional gene repertoire in Jianghan chickens. Despite the absence of antibiotic supplementation, the intestinal microbial community of Jianghan chickens still demonstrates a profile of antibiotic resistance genes similar to that of intensively reared chickens, suggesting resistance genes are prevalent in free-ranging poultry. Moreover, Jianghan and intensively reared chickens host major resistance genes differently, an aspect seldom explored between free-range and pastured chickens. Furthermore, among the 829 isolates, three strains of P. acidilatici exhibited strong probiotic potential. These findings provide insights into the unique gut microbiota of Jianghan chickens and highlight potential probiotic strains offering benefits to the host. Video Abstract.
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Microbioma Gastrointestinal , Probióticos , Animales , Pollos/microbiología , Microbioma Gastrointestinal/genética , Metagenoma , Pediococcus/genética , Antibacterianos/farmacología , Bacteroidetes/genéticaRESUMEN
BACKGROUND: Peripheral nerve injury (PNI) presents a significant clinical challenge, leading to enduring sensory-motor impairments. While mesenchymal stem cell (MSC)-based therapy holds promise for PNI treatment, enhancing its neurotrophic effects remains crucial. Platelet-rich plasma-derived exosomes (PRP-Exo), rich in bioactive molecules for intercellular communication, offer potential for modulating cellular biological activity. METHODS: PRP-Exo was isolated, and its impact on MSC viability was evaluated. The effects of PRP-Exo-treated MSCs (MSCPExo) on Schwann cells (SCs) from injured sciatic nerves and human umbilical vein endothelial cells (HUVECs) were assessed. Furthermore, the conditioned medium from MSCPExo (MSCPExo-CM) was analyzed using a cytokine array and validated through ELISA and Western blot. RESULTS: PRP-Exo enhanced MSC viability. Coculturing MSCPExo with SCs ameliorated apoptosis and promoted SC proliferation following PNI. Similarly, MSCPExo-CM exhibited pro-proliferative, migratory, and angiogenic effects. Cytokine array analysis identified 440 proteins in the MSCPExo secretome, with 155 showing upregulation and 6 showing downregulation, many demonstrating potent pro-regenerative properties. ELISA confirmed the enrichment of several angiotrophic and neurotrophic factors. Additionally, Western blot analysis revealed the activation of the PI3K/Akt signaling pathway in MSCPExo. CONCLUSION: Preconditioning MSCs with PRP-Exo enhanced the paracrine function, particularly augmenting neurotrophic and pro-angiogenic secretions, demonstrating an improved potential for neural repair.
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Exosomas , Células Madre Mesenquimatosas , Plasma Rico en Plaquetas , Humanos , Exosomas/metabolismo , Células Endoteliales , Fosfatidilinositol 3-Quinasas/metabolismo , Citocinas/metabolismo , Regeneración NerviosaRESUMEN
Peripheral nerve injury (PNI) remains a severe clinical problem with debilitating consequences. Mesenchymal stem cell (MSC)-based therapy is promising, but the problems of poor engraftment and insufficient neurotrophic effects need to be overcome. Herein, we isolated platelet-rich plasma-derived exosomes (PRP-Exos), which contain abundant bioactive molecules, and investigated their potential to increase the regenerative capacity of MSCs. We observed that PRP-Exos significantly increased MSC proliferation, viability, and mobility, decreased MSC apoptosis under stress, maintained MSC stemness, and attenuated MSC senescence. In vivo, PRP-Exo-treated MSCs (pExo-MSCs) exhibited an increased retention rate and heightened therapeutic efficacy, as indicated by increased axonal regeneration, remyelination, and recovery of neurological function in a PNI model. In vitro, pExo-MSCs coculture promoted Schwann cell proliferation and dorsal root ganglion axon growth. Moreover, the increased neurotrophic behaviour of pExo-MSCs was mediated by trophic factors, particularly glia-derived neurotrophic factor (GDNF), and PRP-Exos activated the PI3K/Akt signalling pathway in MSCs, leading to the observed phenotypes. These findings demonstrate that PRP-Exos may be novel agents for increasing the ability of MSCs to promote neural repair and regeneration in patients with PNI.
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Exosomas , Células Madre Mesenquimatosas , Traumatismos de los Nervios Periféricos , Plasma Rico en Plaquetas , Humanos , Exosomas/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Regeneración Nerviosa , Traumatismos de los Nervios Periféricos/terapiaRESUMEN
A simplified inoculum agent, only comprising Bacillus subtilis and Aspergillus niger, was utilized for industrial-scale cow-manure composting to investigate its impact on composting performance and microbiome. Inoculants elevated the average and peak temperatures by up to 7 and 10 °C, respectively, during the thermophilic stage, reduced organic matter content, and raised germination index. Inoculation also extended the period of composting above 50 °C from 12 to 26 days. Sequencing unveiled significant shifts in microbial diversity, composition, and function. Aspergillus thrived during the mesophilic phase, potentially initiating composting, whereas Bacillus, Lysinibacillus, and Clostridium were enriched during the thermophilic stage. Metagenomic sequencing revealed an increased abundance of carbohydrate-active enzymes and glycometabolism-related genes responsible for lignocellulose degradation and heat generation after inoculation. These enriched microbes and functional genes contributed to organic matter degradation and temperature maintenance during thermophilic stage, expediting composting. This suggests the effectiveness of this simplified inoculum in industrial-level cow-manure composting.
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Bacillus , Compostaje , Microbiota , Animales , Femenino , Bovinos , Estiércol , Suelo , Microbiota/genéticaRESUMEN
Parasitoid wasps control pests via a precise attack leading to the death of the pest. However, parasitoid larvae exhibit self-protection strategies against bracovirus-induced reactive oxygen species impairment. This has a detrimental effect on pest control. Here, we report a strategy for simulating Microplitis bicoloratus bracovirus using Mix-T dsRNA targeting 14 genes associated with transcription, translation, cell-cell communication, and humoral signaling pathways in the host, and from wasp extracellular superoxide dismutases. We implemented either one-time feeding to the younger instar larvae or spraying once on the corn leaves, to effectively control the invading pest Spodoptera frugiperda. This highlights the conserved principle of "biological pest control," as elucidated by the triple interaction of parasitoid-bracovirus-host in a cooperation strategy of bracovirus against its pest host.