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1.
Front Plant Sci ; 15: 1337560, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38988636

RESUMEN

Over the years, thrips have transitioned from a minor nuisance to a major problem, significantly impacting the yield and quality of cotton. Unmanned aerial vehicles (UAVs) for plant protection have emerged as an effective alternative to traditional pesticide spraying equipment. UAVs offer advantages such as avoiding crop damage and enhancing pesticide deposition on the plants and have become the primary choice for pesticide application in cotton fields. In this study, a 2-year field experiment found that the thrips population in a cotton field in Xinjiang, China, exhibited gradual growth during the early flowering phase, peaking in late July. The thrips population gradually shifted from the lower canopy to the upper canopy as the cotton flowers opened layer by layer. From 09:00 to 11:00 (GMT+8) and 19:00 to 21:00 (GMT+8), thrips mainly flew outside the flowers, while from 17:00 to 19:00 (GMT+8), they mostly inhabited the inner whorls of flowers. The insecticides 10% cyantraniliprole oil dispersion and 10% spinetoram suspension concentrate, sprayed by UAV, had the best control effect on thrips, with 80.51% and 79.22% control effect after 7 days of spraying, respectively. The optimal spraying time for 10% cyantraniliprole oil dispersion was 19:00 (GMT+8), and the control effect on thrips reached 91.16% at 7 days of spraying. During the cotton flowering period, thrips inhabited flowers in the evening and flew outside during the day. The best control effect on thrips was achieved with UAV-sprayed 10% cyantraniliprole oil dispersion at 19:00 (GMT+8).

2.
J Hazard Mater ; 476: 135145, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38991638

RESUMEN

Increasing frequency and intensity of cyanobacterial blooms in water sources is a growing global issue. Algicides are usually implemented in summer or autumn when blooms break out, however, the blooms will form again when algicide's concentration declines to a certain extent. Preventing the recovery and growth of cyanobacteria in early spring may be conducive to abatement of the blooms in summer or autumn. In this study solid sodium percarbonate (SPC) was used as an algicide to suppress recovery and growth of Pseudanabaena sp., a common odour-producing cyanobacterium, in early spring (12 °C). Results showed that 3.0 and 6.0 mg/L SPC were able to kill most of the algal cells after 12 h treatment at 12 °C, and the residual cells gradually died during the re-cultivation period at 25 °C. As a control, although SPC also caused most of algal cells to lyse at 25 °C, regrowth of cells was found during the period of re-cultivation at 25 °C. Transcriptomic analysis revealed that the dysregulated genes were strongly associated with translation and photosynthesis after SPC treatment. All differentially expressed unigenes related to translation and photosynthesis were down-regulated after SPC oxidation at 12 °C, whereas key genes associated with translation and photosynthesis were upregulated after SPC treatment at 25 °C.

3.
Int Wound J ; 21(7): e14965, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38994878

RESUMEN

Although potential risk factors for sternal wound infection (SWI) have been extensively studied, the onset time of SWI and different risk factors for superficial and deep SWI were rarely reported. This nested case-control study aims to compare the onset time and contributors between superficial and deep SWI. Consecutive adult patients who underwent cardiac surgery through median sternotomy in a single center from January 2011 to January 2021 constituted the cohort. The case group was those who developed SWI as defined by CDC and controls were matched 6:1 per case. Kaplan-Meier analysis, LASSO and univariate and multivariate Cox regressions were performed. A simple nomogram was established for clinical prediction of the risk of SWI. The incidence of SWI was 1.1% (61 out of 5471) in our cohort. Totally 366 controls were matched to 61 cases. 26.2% (16 of 61) SWI cases were deep SWI. The median onset time of SWI was 35 days. DSWI had a longer latency than SSWI (median time 46 days vs. 32 days, p = 0.032). Kaplan-Meier analyses showed different time-to-SWI between patients with and without DM (p = 0.0011) or MI (p = 0.0019). Multivariate Cox regression showed that BMI (HR = 1.083, 95% CI: 1.012-1.116, p = 0.022), DM (HR = 2.041, 95% CI: 1.094-3.805, p = 0.025) and MI (HR = 2.332, 95% CI: 1.193-4.557, p = 0.013) were independent risk factors for SWI. Superficial SWI was only associated with BMI (HR = 1.089, 95% CI: 1.01-1.175, p = 0.027), while deep SWI was associated with DM (HR = 3.271, 95% CI: 1.036-10.325, p = 0.043) and surgery time (HR = 1.004, 95% CI: 1.001-1.008, p = 0.027). The nomogram for SWI prediction had an AUC of 0.67, good fitness and clinical effectiveness as shown by the calibration curve and decision curve analyses. BMI, DM and MI were independent risk factors for SWI. DSWI had a longer latency and different risk factors compared to SSWI. The nomogram showed a fair performance and good effectiveness for the clinical prediction of SWI.


Asunto(s)
Esternotomía , Infección de la Herida Quirúrgica , Humanos , Masculino , Estudios de Casos y Controles , Esternotomía/efectos adversos , Femenino , Factores de Riesgo , Persona de Mediana Edad , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Anciano , Factores de Tiempo , Incidencia , Esternón/cirugía , Procedimientos Quirúrgicos Cardíacos/efectos adversos
4.
Cancer ; 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39012906

RESUMEN

BACKGROUND: Understanding the impact of clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) on solid tumor risk and mortality can shed light on novel cancer pathways. METHODS: The authors analyzed whole genome sequencing data from the Trans-Omics for Precision Medicine Women's Health Initiative study (n = 10,866). They investigated the presence of CHIP and mCA and their association with the development and mortality of breast, lung, and colorectal cancers. RESULTS: CHIP was associated with higher risk of breast (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.03-1.64; p = .02) but not colorectal (p = .77) or lung cancer (p = .32). CHIP carriers who developed colorectal cancer also had a greater risk for advanced-stage (p = .01), but this was not seen in breast or lung cancer. CHIP was associated with increased colorectal cancer mortality both with (HR, 3.99; 95% CI, 2.41-6.62; p < .001) and without adjustment (HR, 2.50; 95% CI, 1.32-4.72; p = .004) for advanced-stage and a borderline higher breast cancer mortality (HR, 1.53; 95% CI, 0.98-2.41; p = .06). Conversely, mCA (cell fraction [CF] >3%) did not correlate with cancer risk. With higher CFs (mCA >5%), autosomal mCA was associated with increased breast cancer risk (HR, 1.39; 95% CI, 1.06-1.83; p = .01). There was no association of mCA (>3%) with breast, colorectal, or lung mortality except higher colon cancer mortality (HR, 2.19; 95% CI, 1.11-4.3; p = .02) with mCA >5%. CONCLUSIONS: CHIP and mCA (CF >5%) were associated with higher breast cancer risk and colorectal cancer mortality individually. These data could inform on novel pathways that impact cancer risk and lead to better risk stratification.

5.
ACS Appl Mater Interfaces ; 16(25): 32445-32455, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38870411

RESUMEN

Flexible sensors are of great interest due to their potential applications in human physiological signal monitoring, wearable devices, and healthcare. However, sensor devices employed for cardiovascular testing are normally bulky and expensive, which hamper wearability and point-of-care use. Herein, we report a simple method for preparing multifunctional flexible sensors using hydrazine hydrate (N2H4·H2O) as the reducing agent, graphene as the active material, and polyethylene (PE) tape as the encapsulation material. The flexible sensor produced with this method has a low detection limit of 100 mg, a fast response and recovery time of 40 and 20 ms, and shows no performance degradation even after up to 30,000 motion cycles. The sensors we have developed are capable of monitoring the pulse with relative accuracy, which presents an opportunity to replace bulky devices and normalize cardiovascular testing in the future. In order to further broaden the application field, the sensor is installed as a sensor array to recognize objects of different weights and shapes, showing that the sensor has excellent application potential in wearable artificial intelligence.


Asunto(s)
Grafito , Dispositivos Electrónicos Vestibles , Grafito/química , Humanos , Monitoreo Fisiológico/instrumentación , Monitoreo Fisiológico/métodos , Hidrazinas/química , Pulso Arterial , Polietileno/química , Técnicas Biosensibles/instrumentación
6.
medRxiv ; 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38699360

RESUMEN

Mosaic loss of Y (mLOY) is the most common somatic chromosomal alteration detected in human blood. The presence of mLOY is associated with altered blood cell counts and increased risk of Alzheimer's disease, solid tumors, and other age-related diseases. We sought to gain a better understanding of genetic drivers and associated phenotypes of mLOY through analyses of whole genome sequencing of a large set of genetically diverse males from the Trans-Omics for Precision Medicine (TOPMed) program. This approach enabled us to identify differences in mLOY frequencies across populations defined by genetic similarity, revealing a higher frequency of mLOY in the European American (EA) ancestry group compared to those of Hispanic American (HA), African American (AA), and East Asian (EAS) ancestry. Further, we identified two genes ( CFHR1 and LRP6 ) that harbor multiple rare, putatively deleterious variants associated with mLOY susceptibility, show that subsets of human hematopoietic stem cells are enriched for activity of mLOY susceptibility variants, and that certain alleles on chromosome Y are more likely to be lost than others.

7.
Front Public Health ; 12: 1347693, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38813407

RESUMEN

Aims: In the year 2021, human brucellosis ranked fifth in terms of the number of cases among all statutorily notifiable infectious diseases in China, thus remaining a significant concern for public health. This study aims to provide insights into the financial burden of human brucellosis by examining hospital stays and associated costs for affected individuals. Methods: In this retrospective study, we gathered updated data from 467 inpatient cases primarily diagnosed with human brucellosis at eight major tertiary hospitals in Beijing, China, spanning from 2013 to 2023. To comprehensively explore the economic impact on individuals, we not only analyzed the duration of hospital stays and total costs but also examined various charge types, including drug, lab test, medical imaging, medical treatment, surgical procedures, medical supplies and consumables, inpatient bed care, nursing services, and other services costs. Statistical analysis was employed to compare differences among gender, age, ethnicity, type of health insurance, condition at admission, comorbidity index, the performance of surgery, and the site of infection. Results: Both the length of stay and total cost exhibited significant variations among insurance, surgery, and infection site groups. Utilization categories demonstrated significant differences between patients who underwent surgery and those who did not, as well as across different infection sites. Furthermore, multiple linear regression analysis revealed that the condition at admission, Elixhauser comorbidity index, infection site, and surgery influenced both hospital stay and total cost. In addition, age and insurance type were associated with total costs. Conclusion: By delving into various utilization categories, we have addressed a significant gap in the literature. Our findings provide valuable insights for optimizing the allocation and management of health resources based on the influencing factors identified in this study.


Asunto(s)
Brucelosis , Tiempo de Internación , Humanos , Femenino , Masculino , Tiempo de Internación/economía , Tiempo de Internación/estadística & datos numéricos , Estudios Retrospectivos , Brucelosis/economía , Brucelosis/diagnóstico , Brucelosis/epidemiología , Persona de Mediana Edad , Adulto , Beijing , Anciano , Pacientes Internos/estadística & datos numéricos , Adolescente , Adulto Joven , Costos de la Atención en Salud/estadística & datos numéricos , China/epidemiología
8.
Cell Stem Cell ; 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38772378

RESUMEN

Cell-based ex vivo gene therapy in solid organs, especially the liver, has proven technically challenging. Here, we report a feasible strategy for the clinical application of hepatocyte therapy. We first generated high-quality autologous hepatocytes through the large-scale expansion of patient-derived hepatocytes. Moreover, the proliferating patient-derived hepatocytes, together with the AAV2.7m8 variant identified through screening, enabled CRISPR-Cas9-mediated targeted integration efficiently, achieving functional correction of pathogenic mutations in FAH or OTC. Importantly, these edited hepatocytes repopulated the injured mouse liver at high repopulation levels and underwent maturation, successfully treating mice with tyrosinemia following transplantation. Our study combines ex vivo large-scale cell expansion and gene editing in patient-derived transplantable hepatocytes, which holds potential for treating human liver diseases.

10.
BMC Microbiol ; 24(1): 97, 2024 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-38521894

RESUMEN

BACKGROUND: Primary nephrotic syndrome (PNS) is a common glomerular disease in children. Clostridium butyricum (C. butyricum), a probiotic producing butyric acid, exerts effective in regulating inflammation. This study was designed to elucidate the effect of C. butyricum on PNS inflammation through the gut-kidney axis. METHOD: BALB/c mice were randomly divided into 4 groups: normal control group (CON), C. butyricum control group (CON+C. butyricum), PNS model group (PNS), and PNS with C. butyricum group (PNS+C. butyricum). The PNS model was established by a single injection of doxorubicin hydrochloride (DOX) through the tail vein. After 1 week of modeling, the mice were treated with C. butyricum for 6 weeks. At the end of the experiment, the mice were euthanized and associated indications were investigated. RESULTS: Since the successful modeling of the PNS, the 24 h urine protein, blood urea nitrogen (BUN), serum creatinine (SCr), urine urea nitrogen (UUN), urine creatinine (UCr), lipopolysaccharides (LPS), pro-inflammatory interleukin (IL)-6, IL-17A were increased, the kidney pathological damage was aggravated, while a reduction of body weights of the mice and the anti-inflammatory IL-10 significantly reduced. However, these abnormalities could be dramatically reversed by C. butyricum treatment. The crucial Th17/Tregs axis in PNS inflammation also was proved to be effectively regulated by C. butyricum treatment. This probiotic intervention notably affected the expression levels of signal transducer and activator of transcription 3 (STAT3), Heme oxygenase-1 (HO-1) protein, and retinoic acid-related orphan receptor gamma t (RORγt). 16S rRNA sequencing showed that C. butyricum could regulate the composition of the intestinal microbial community and found Proteobacteria was more abundant in urine microorganisms in mice with PNS. Short-chain fatty acids (SCFAs) were measured and showed that C. butyricum treatment increased the contents of acetic acid, propionic acid, butyric acid in feces, acetic acid, and valeric acid in urine. Correlation analysis showed that there was a closely complicated correlation among inflammatory indicators, metabolic indicators, microbiota, and associated metabolic SCFAs in the gut-kidney axis. CONCLUSION: C. butyricum regulates Th17/Tregs balance via the gut-kidney axis to suppress the immune inflammatory response in mice with PNS, which may potentially contribute to a safe and inexpensive therapeutic agent for PNS.


Asunto(s)
Clostridium butyricum , Síndrome Nefrótico , Humanos , Niño , Ratones , Animales , ARN Ribosómico 16S , Inflamación , Riñón , Ácidos Grasos Volátiles , Butiratos , Interleucina-6 , Acetatos
11.
World J Gastrointest Surg ; 16(2): 438-450, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38463372

RESUMEN

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR), a composite inflammatory biomarker, is associated with the prognosis in patients with colorectal tumors. However, whether the NLR can be used as a predictor of symptomatic postoperative anastomotic leakage (AL) in elderly patients with colon cancer is unclear. AIM: To assess the role of the NLR in predicting the occurrence of symptomatic AL after surgery in elderly patients with colon cancer. METHODS: Data from elderly colon cancer patients who underwent elective radical colectomy with anastomosis at three centers between 2018 and 2022 were retrospectively analyzed. Receiver operating characteristic curve analysis was performed to determine the best predictive cutoff value for the NLR. Twenty-two covariates were matched using a 1:1 propensity score matching method, and univariate and multivariate logistic regression analyses were used to determine risk factors for the development of postoperative AL. RESULTS: Of the 577 patients included, 36 (6.2%) had symptomatic AL. The optimal cutoff value of the NLR for predicting AL was 2.66. After propensity score matching, the incidence of AL was significantly greater in the ≥ 2.66 NLR subgroup than in the < 2.66 NLR subgroup (11.5% vs 2.5%; P = 0.012). Univariate logistic regression analysis revealed statistically significant correlations between blood transfusion intraoperatively and within 2 d postoperatively, preoperative albumin concentration, preoperative prognostic nutritional index, and preoperative NLR and AL occurrence (P < 0.05); multivariate logistic regression analysis revealed that an NLR ≥ 2.66 [odds ratio (OR) = 5.51; 95% confidence interval (CI): 1.50-20.26; P = 0.010] and blood transfusion intraoperatively and within 2 d postoperatively (OR = 2.52; 95%CI: 0.88-7.25; P = 0.049) were risk factors for the occurrence of symptomatic AL. CONCLUSION: A preoperative NLR ≥ 2.66 and blood transfusion intraoperatively and within 2 d postoperatively are associated with a higher incidence of postoperative symptomatic AL in elderly patients with colon cancer. The preoperative NLR has predictive value for postoperative symptomatic AL after elective surgery in elderly patients with colon cancer.

12.
Pol J Microbiol ; 73(1): 59-68, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38437464

RESUMEN

This study aimed to investigate the disparities between metagenomic next-generation sequencing (mNGS) and conventional culture results in patients with bronchiectasis. Additionally, we sought to investigate the correlation between the clinical characteristics of patients and their microbiome profiles. The overarching goal was to enhance the effective management and treatment of bronchiectasis patients, providing a theoretical foundation for healthcare professionals. A retrospective survey was conducted on 67 bronchiectasis patients admitted to The First Hospital of Jiaxing from October 2019 to March 2023. Clinical baseline information, inflammatory indicators, and pathogen detection reports, including mNGS, conventional blood culture, bronchoalveolar lavage fluid (BALF) culture, and sputum culture results, were collected. By comparing the results of mNGS and conventional culture, the differences in pathogen detection rate and pathogen types were explored, and the diagnostic performance of mNGS compared to conventional culture was evaluated. Based on the various pathogens detected by mNGS, the association between clinical characteristics of bronchiectasis patients and mNGS microbiota results was analyzed. The number and types of pathogens detected by mNGS were significantly larger than those detected by conventional culture. The diagnostic efficacy of mNGS was significantly superior to conventional culture for all types of pathogens, particularly in viral detection (p < 0.01). Regarding pathogen detection rate, the bacteria with the highest detection rate were Pseudomonas aeruginosa (17/58) and Haemophilus influenzae (11/58); the fungus with the highest detection rate was Aspergillus fumigatus (10/21), and the virus with the highest detection rate was human herpes virus 4 (4/11). Differences were observed between the positive and negative groups for P. aeruginosa in terms of common scoring systems for bronchiectasis and whether the main symptom of bronchiectasis manifested as thick sputum (p < 0.05). Significant distinctions were also noted between the positive and negative groups for A. fumigatus regarding Reiff score, neutrophil percentage, bronchiectasis etiology, and alterations in treatment plans following mNGS results reporting (p < 0.05). Notably, 70% of patients with positive A. fumigatus infection opted to change their treatment plans. The correlation study between clinical characteristics of bronchiectasis patients and mNGS microbiological results revealed that bacteria, such as P. aeruginosa, and fungi, such as A. fumigatus, were associated with specific clinical features of patients. This underscored the significance of mNGS in guiding personalized treatment approaches. mNGS could identify multiple pathogens in different types of bronchiectasis samples and was a rapid and effective diagnostic tool for pathogen identification. Its use was recommended for diagnosing the causes of infections in bronchiectasis patients.


Asunto(s)
Aspergilosis , Bronquiectasia , Microbiota , Humanos , Estudios Retrospectivos , Microbiota/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Bronquiectasia/diagnóstico
13.
Int J Biol Macromol ; 265(Pt 2): 131100, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38521308

RESUMEN

Selenylation modification has been widely developed to improve the biological effects of natural polysaccharides. In this study, a purified new polysaccharide (MSP-4) was isolated from Morchella Sextelata, and selenized into SeMSP-4 using the HNO3-Na2SeO3 method. The selenium (Se) content of SeMSP-4 was 101.81 ± 9.90 mg/kg, and the molecular weight of SeMSP-4 was 1.23 × 105 Da. The FT-IR, XRD and AFM results showed that MSP-4 was successfully combined with the Se element. The structure characters of SeMSP-4 were analyzed by methylation analysis combined with 1D and 2D NMR spectroscopy. And, the radical scavenging test revealed that SeMSP-4 exhibited higher antioxidant capacities in vitro than MSP-4. The cytotoxicity analysis indicated that SeMSP-4 could dose-dependently inhibit the proliferation of HepG2 and HeLa cells, but did not show a cytotoxic effect on normal cells (HEK293). Furthermore, SeMSP-4 stimulation significantly increased the macrophage viability and enhanced NO production in macrophage cells. This study suggested that SeMSP-4 could be utilized as a potential selenium source with antioxidant, antitumor, and immunostimulatory activities.


Asunto(s)
Antioxidantes , Ascomicetos , Selenio , Humanos , Antioxidantes/farmacología , Antioxidantes/química , Selenio/farmacología , Selenio/química , Células HeLa , Células HEK293 , Espectroscopía Infrarroja por Transformada de Fourier , Polisacáridos/farmacología , Polisacáridos/química
14.
Transl Oncol ; 44: 101937, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38547613

RESUMEN

BACKGROUND: Soft tissue sarcoma, a malignant tumor arising from mesenchymal tissues with poor prognosis. 5'-Nucleotidase Domain Containing 2 (NT5DC2) is a novel oncogene, and the precise involvement of NT5DC2 in soft tissue sarcoma were still undefined. Hence, our study aims to investigate NT5DC2 functions in soft tissue sarcoma progression. METHODS: The tumor immune single-cell hub 2 (TISCH2) website, The Cancer Genome Atlas (TCGA) pan-cancer or sarcoma and Gene Expression Omnibus (GEO, GSE21122) databases were applied to visualize the NT5DC2 status in the sarcoma databases. The NT5DC2 protein expression in sarcoma tissues in our hospital was detected by using immunohistochemistry (IHC) and analyzed the associations between NT5DC2 expression and clinicopathological parameters. Real-time quantitative polymerase chain reaction (RT-qPCR), colony formation, 5-ethynyl-2'-deoxyuridine (EdU) assay, wound healing, transwell, flow cytometry and xenograft model were used to elucidate the effects of NT5DC2 downregulated by lentivirus in sarcoma cell. RESULTS: The TISCH2 website detection found that NT5DC2 expression is enriched in malignant cells in sarcoma single-cell database. Furthermore, the TCGA-sarcoma database indicated that NT5DC2 expression correlates with metastasis, positive margin status, prognosis, and diagnostic value. Additionally, IHC staining showed that 40 % of soft tissue sarcoma patients present high expression of NT5DC2, and NT5DC2 upregulation is closely associated with poor prognosis. Functional verification analysis further revealed that downregulating NT5DC2 expression can suppress sarcoma progression through the ECM-receptor interaction pathway. CONCLUSION: Low expression of NT5DC2 predicts a favorable prognosis in soft tissue sarcoma, and downregulated NT5DC2 expression can suppress sarcoma cell progression through the ECM-receptor interaction pathway.

15.
bioRxiv ; 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38496419

RESUMEN

Amniogenesis, a process critical for continuation of healthy pregnancy, is triggered in a collection of pluripotent epiblast cells as the human embryo implants. Previous studies have established that BMP signaling is a major driver of this lineage specifying process, but the downstream BMP-dependent transcriptional networks that lead to successful amniogenesis remain to be identified. This is, in part, due to the current lack of a robust and reproducible model system that enables mechanistic investigations exclusively into amniogenesis. Here, we developed an improved model of early amnion specification, using a human pluripotent stem cell-based platform in which the activation of BMP signaling is controlled and synchronous. Uniform amniogenesis is seen within 48 hours after BMP activation, and the resulting cells share transcriptomic characteristics with amnion cells of a gastrulating human embryo. Using detailed time-course transcriptomic analyses, we established a previously uncharacterized BMP-dependent amniotic transcriptional cascade, and identified markers that represent five distinct stages of amnion fate specification; the expression of selected markers was validated in early post-implantation macaque embryos. Moreover, a cohort of factors that could potentially control specific stages of amniogenesis was identified, including the transcription factor TFAP2A. Functionally, we determined that, once amniogenesis is triggered by the BMP pathway, TFAP2A controls the progression of amniogenesis. This work presents a temporally resolved transcriptomic resource for several previously uncharacterized amniogenesis states and demonstrates a critical intermediate role for TFAP2A during amnion fate specification.

16.
Clin Transl Med ; 14(2): e1586, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38372422

RESUMEN

BACKGROUND: Osteosarcoma (OSA) presents a clinical challenge and has a low 5-year survival rate. Currently, the lack of advanced stratification models makes personalized therapy difficult. This study aims to identify novel biomarkers to stratify high-risk OSA patients and guide treatment. METHODS: We combined 10 machine-learning algorithms into 101 combinations, from which the optimal model was established for predicting overall survival based on transcriptomic profiles for 254 samples. Alterations in transcriptomic, genomic and epigenomic landscapes were assessed to elucidate mechanisms driving poor prognosis. Single-cell RNA sequencing (scRNA-seq) unveiled genes overexpressed in OSA cells as potential therapeutic targets, one of which was validated via tissue staining, knockdown and pharmacological inhibition. We characterized changes in multiple phenotypes, including proliferation, colony formation, migration, invasion, apoptosis, chemosensitivity and in vivo tumourigenicity. RNA-seq and Western blotting elucidated the impact of squalene epoxidase (SQLE) suppression on signalling pathways. RESULTS: The artificial intelligence-derived prognostic index (AIDPI), generated by our model, was an independent prognostic biomarker, outperforming clinicopathological factors and previously published signatures. Incorporating the AIDPI with clinical factors into a nomogram improved predictive accuracy. For user convenience, both the model and nomogram are accessible online. Patients in the high-AIDPI group exhibited chemoresistance, coupled with overexpression of MYC and SQLE, increased mTORC1 signalling, disrupted PI3K-Akt signalling, and diminished immune infiltration. ScRNA-seq revealed high expression of MYC and SQLE in OSA cells. Elevated SQLE expression correlated with chemoresistance and worse outcomes in OSA patients. Therapeutically, silencing SQLE suppressed OSA malignancy and enhanced chemosensitivity, mediated by cholesterol depletion and suppression of the FAK/PI3K/Akt/mTOR pathway. Furthermore, the SQLE-specific inhibitor FR194738 demonstrated anti-OSA effects in vivo and exhibited synergistic effects with chemotherapeutic agents. CONCLUSIONS: AIDPI is a robust biomarker for identifying the high-risk subset of OSA patients. The SQLE protein emerges as a metabolic vulnerability in these patients, providing a target with translational potential.


Asunto(s)
Neoplasias Óseas , Osteosarcoma , Escualeno-Monooxigenasa , Humanos , Inteligencia Artificial , Biomarcadores , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/genética , Fosfatidilinositol 3-Quinasas , Pronóstico , Proteínas Proto-Oncogénicas c-akt , Escualeno-Monooxigenasa/genética , Escualeno-Monooxigenasa/metabolismo
17.
Eur J Neurosci ; 59(10): 2563-2576, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38379501

RESUMEN

Parkinson's disease (PD), being the second largest neurodegenerative disease, poses challenges in early detection, resulting in a lack of timely treatment options to effectively manage the disease. By the time clinical diagnosis becomes possible, more than 60% of dopamine neurons in the substantia nigra (SN) of patients have already degenerated. Therefore, early diagnosis or identification of warning signs is crucial for the prompt and timely beginning of the treatment. However, conducting invasive or complex diagnostic procedures on asymptomatic patients can be challenging, making routine blood tests a more feasible approach in such cases. Numerous studies have been conducted over an extended period to search for effective diagnostic biomarkers in blood samples. However, thus far, no highly effective biomarkers have been confirmed. Besides classical proteins like α-synuclein (α-syn), phosphorylated α-syn and oligomeric α-syn, other molecules involved in disease progression should also be given equal attention. In this review, we will not only discuss proposed biomarkers that are currently under investigation but also delve into the mechanisms underlying the disease, focusing on processes such as α-syn misfolding, intercellular transmission and the crossing of the blood-brain barrier (BBB). Our aim is to provide an updated overview of molecules based on these processes that may potentially serve as blood biomarkers.


Asunto(s)
Biomarcadores , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/sangre , Enfermedad de Parkinson/diagnóstico , Biomarcadores/sangre , alfa-Sinucleína/sangre , Barrera Hematoencefálica/metabolismo
18.
Am J Respir Cell Mol Biol ; 70(5): 364-378, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38300138

RESUMEN

Various infections trigger a storm of proinflammatory cytokines in which IL-6 acts as a major contributor and leads to diffuse alveolar damage in patients. However, the metabolic regulatory mechanisms of IL-6 in lung injury remain unclear. Polyriboinosinic-polyribocytidylic acid [poly(I:C)] activates pattern recognition receptors involved in viral sensing and is widely used in alternative animal models of RNA virus-infected lung injury. In this study, intratracheal instillation of poly(I:C) with or without an IL-6-neutralizing antibody model was combined with metabonomics, transcriptomics, and so forth to explore the underlying molecular mechanisms of IL-6-exacerbated lung injury. We found that poly(I:C) increased the IL-6 concentration, and the upregulated IL-6 further induced lung ferroptosis, especially in alveolar epithelial type II cells. Meanwhile, lung regeneration was impaired. Mechanistically, metabolomic analysis showed that poly(I:C) significantly decreased glycolytic metabolites and increased bile acid intermediate metabolites that inhibited the bile acid nuclear receptor farnesoid X receptor (FXR), which could be reversed by IL-6-neutralizing antibody. In the ferroptosis microenvironment, IL-6 receptor monoclonal antibody tocilizumab increased FXR expression and subsequently increased the Yes-associated protein (YAP) concentration by enhancing PKM2 in A549 cells. FXR agonist GW4064 and liquiritin, a potential natural herbal ingredient as an FXR regulator, significantly attenuated lung tissue inflammation and ferroptosis while promoting pulmonary regeneration. Together, the findings of the present study provide the evidence that IL-6 promotes ferroptosis and impairs regeneration of alveolar epithelial type II cells during poly(I:C)-induced murine lung injury by regulating the FXR-PKM2-YAP axis. Targeting FXR represents a promising therapeutic strategy for IL-6-associated inflammatory lung injury.


Asunto(s)
Ferroptosis , Interleucina-6 , Pulmón , Poli I-C , Receptores Citoplasmáticos y Nucleares , Ferroptosis/efectos de los fármacos , Animales , Poli I-C/farmacología , Interleucina-6/metabolismo , Ratones , Receptores Citoplasmáticos y Nucleares/metabolismo , Pulmón/patología , Pulmón/metabolismo , Pulmón/efectos de los fármacos , Ratones Endogámicos C57BL , Masculino , Lesión Pulmonar/metabolismo , Lesión Pulmonar/patología , Lesión Pulmonar/tratamiento farmacológico , Humanos , Transducción de Señal/efectos de los fármacos
20.
Biomimetics (Basel) ; 9(1)2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38275458

RESUMEN

The routine use of prosthetic hands significantly enhances amputees' daily lives, yet it often introduces cognitive load and reduces reaction speed. To address this issue, we introduce a wearable semi-autonomous hierarchical control framework tailored for amputees. Drawing inspiration from the visual processing stream in humans, a fully autonomous bionic controller is integrated into the prosthetic hand control system to offload cognitive burden, complemented by a Human-in-the-Loop (HIL) control method. In the ventral-stream phase, the controller integrates multi-modal information from the user's hand-eye coordination and biological instincts to analyze the user's movement intention and manipulate primitive switches in the variable domain of view. Transitioning to the dorsal-stream phase, precise force control is attained through the HIL control strategy, combining feedback from the prosthetic hand's sensors and the user's electromyographic (EMG) signals. The effectiveness of the proposed interface is demonstrated by the experimental results. Our approach presents a more effective method of interaction between a robotic control system and the human.

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