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1.
Accid Anal Prev ; 206: 107695, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38972258

RESUMEN

Rear-end (RE) crashes are notably prevalent and pose a substantial risk on freeways. This paper explores the correlation between speed difference among the following and leading vehicles (Δν) and RE crash risk. Three joint models, comprising both uncorrelated and correlated joint random-parameters bivariate probit (RPBP) approaches (statistical methods) and a cross-stitch multilayer perceptron (CS-MLP) network (a data-driven method), were estimated and compared against three separate models: Support Vector Machines (SVM), eXtreme Gradient Boosting (XGBoost), and MLP networks (all data-driven methods). Data on 15,980 two-vehicle RE crashes were collected over a two-year period, from January 1, 2021, to December 31, 2022, considering two possible levels of injury severity: no injury and injury/fatality for both drivers of following and leading vehicles. The comparative performance analysis demonstrates the superior predictive capability of the CS-MLP network over the uncorrelated/correlated joint RPBP model, SVM, XGBoost, and MLP networks in terms of recall, F-1 Score, and AUC. Significantly, numerous shared variables influence the injury severity outcomes for the following and leading vehicles across both statistical and data-driven approaches. Among these factors, the following vehicle (a truck) and the leading vehicle (a passenger car) demonstrate contrasting effects on the injury severity outcomes for both vehicles. Furthermore, the SHapley Additive exPlanations (SHAP) values from the CS-MLP network visually show the relationship between Δν and injury severity, revealing non-linear trends unlike the average effects shown by statistical methods. They indicate that the least injury outcomes for both following and leading vehicles occurs at a Δν of 0 to 10 mph, matching observed patterns in RE crash data. Additionally, a marked variation in the trend of SHAP values for the two vehicles is noted as the speed difference increases. Therefore, the findings affirm the superior performance of joint model development and substantiate the non-linear impacts of speed difference on injury outcomes. The adoption of dynamic speed control measures is recommended to mitigate the injury outcomes involved in two-vehicle RE crashes.

2.
Plant Cell ; 2024 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-38943676

RESUMEN

The cell wall shapes plant cell morphogenesis and affects the plasticity of organ growth. However, the way in which cell wall establishment is regulated by ethylene remains largely elusive. Here, by analyzing cell wall patterns, cell wall composition and gene expression in rice (Oryza sativa, L.) roots, we found that ethylene induces cell wall thickening and the expression of cell wall synthesis-related genes, including CELLULOSE SYNTHASE-LIKE C1, 2, 7, 9, 10 (OsCSLC1, 2, 7, 9, 10) and CELLULOSE SYNTHASE A3, 4, 7, 9 (OsCESA3, 4, 7, 9). Overexpression and mutant analyses revealed that OsCSLC2 and its homologs function in ethylene-mediated induction of xyloglucan biosynthesis mainly in the cell wall of root epidermal cells. Moreover, OsCESA-catalyzed cellulose deposition in the cell wall was enhanced by ethylene. OsCSLC-mediated xyloglucan biosynthesis likely plays an important role in restricting cell wall extension and cell elongation during the ethylene response in rice roots. Genetically, OsCSLC2 acts downstream of ETHYLENE-INSENSITIVE3-LIKE1 (OsEIL1)-mediated ethylene signaling, and OsCSLC1, 2, 7, 9 are directly activated by OsEIL1. Furthermore, the auxin signaling pathway is synergistically involved in these regulatory processes. These findings link plant hormone signaling with cell wall establishment, broadening our understanding of root growth plasticity in rice and other crops.

3.
Nanoscale ; 16(26): 12368-12379, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38873708

RESUMEN

The oxygen evolution reaction (OER) is crucial for applications such as water splitting and rechargeable metal-air batteries. Recent research has focused on improving the activity and stability of OER electrocatalysts through various strategies including structural innovation, heteroatom doping, and conductivity enhancement. Among these, defect engineering has proved particularly effective, allowing precise modulation of the materials' electronic structure at the atomic level. This review addresses defect-rich materials that exhibit superior electrochemical properties for OER applications, with a particular focus on developments from the past five years. The discussion starts with an overview of the OER catalytic mechanism and then delves into the types of defects, synthesis methods, and their impact on electrochemical performance. This review concludes with insights into the rational design and synthesis of advanced electrocatalysts, aiming to improve efficiency and extend operational longevity. The objective is to highlight approaches for creating high-performance OER electrocatalysts that outperform noble-metal based systems in both activity and stability.

4.
Front Psychol ; 15: 1364382, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38836239

RESUMEN

Part-set cuing facilitation and impairment effects are rarely found in spatial memory, which is a challenge to the theories of part-set cuing effects based on lexical stimulus. This study aims to investigate whether there part-set cuing facilitation and impairment effects are present in spatial memory by constructing two types of memory scenes with high and low degrees of interitem associations, achieved by manipulating the presentation of miniatures. This study examined the effects of different part-set cues on free recall, recognition, and reconstruction tasks. The results of two experiments revealed that matrix cues impaired the performance of three recall tasks in memory scenes with a high degree of interitem associations, and scene cues facilitated the reconstruction performance (Experiment 1). Conversely, in memory scenes with a low degree of interitem associations, the impairment effect of matrix cues was not observed in the three recall tasks, but scene cues still facilitated the reconstruction performance (Experiment 2). These findings supported the retrieval strategy disruption hypothesis, the two-mechanism and the multi-mechanism accounts, demonstrating the significance of interitem associations in spatial memory. Furthermore, the results provided direct evidence for the importance of the encoding-retrieval strategy matching principle in spatial memory tasks.

5.
Artículo en Inglés | MEDLINE | ID: mdl-38875459

RESUMEN

Rosa roxburghii (R. roxburghii) is a unique, edible, medicinal fruit rich in vitamin C found in Southwest China. Triadimefon (TDF) is a triazole fungicide that is widely used to control powdery mildew in R. roxburghii. To assess the safety of TDF in R. roxburghii, an LC-MS/MS method was developed for the simultaneous quantification of TDF and its major metabolite, triadimenol (TDN) in R. roxburghii. Both TDF and TDN showed high correlation coefficients (>0.999) for the solvent- and matrix-matched calibrations. The recovery rates of TDF and TDN in R. roxburghii ranged from 90.18% to 100.42%, with a relative standard deviation (RSD) of 1.25%-9.22%. The limit of quantification (LOQ) was 0.01 mg·kg-1. The half-life of TDF in R. roxburghii was between 2.74 and 3.07 days, with terminal residues ranging from < LOQ to 1.84 mg·kg-1. Recommended maximum residue limits (MRLs) and safe pre-harvest intervals (PHIs) for TDF in R. roxburghii were 0.5 mg·kg-1 and 21 days, respectively. This study provides essential data for TDF's safe and judicious use in R. roxburghii production.

6.
Materials (Basel) ; 17(11)2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38893993

RESUMEN

GH4169 alloy/Inconel 718 is extensively utilized in aerospace manufacturing due to its excellent high temperature mechanical properties. Micro-structuring on the workpiece surface can enhance its properties further. Through-mask electrochemical micromachining (TMEMM) is a promising and potential processing method for nickel-based superalloys. It can effectively solve the problem that traditional processing methods are difficult to achieve large-scale, high-precision and efficiency processing of surface micro-structure. This study explores the feasibility of electrochemical machining (ECM) for GH4169 using roll-print mask electrochemical machining with a linear cathode. Electrochemical dissolution characteristics of GH4169 alloy were analyzed in various electrolyte solutions and concentrations. Key parameters including cathode sizes, applied voltage and corrosion time were studied in the roll-print mask electrochemical machining. A qualitative model for micro-pit formation on GH4169 was established. Optimal parameters were determined through experiments: 300 µm mask hole and cathode size, 10 wt% NaNO3 electrolyte, 12 V voltage, 6 s corrosion time. The results demonstrate that the micro-pits with a diameter of 402.3 µm, depth of 92.8 µm and etch factor (EF) of 1.81 show an excellent profile and localization.

7.
Cancer Imaging ; 24(1): 75, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38886866

RESUMEN

OBJECTIVE: The aim of our study is to find a better way to identify a group of papillary thyroid carcinoma (PTC) with more aggressive behaviors and to provide a prediction model for lymph node metastasis to assist in clinic practice. METHODS: Targeted sequencing of DNA/RNA was used to detect genetic alterations. Gene expression level was measured by quantitative real-time PCR, western blotting or immunohistochemistry. CCK8, transwell assay and flow cytometry were used to investigate the effects of concomitant gene alterations in PTC. LASSO-logistics regression algorithm was used to construct a nomogram model integrating radiomic features, mutated genes and clinical characteristics. RESULTS: 172 high-risk variants and 7 fusion types were detected. The mutation frequencies in BRAF, TERT, RET, ATM and GGT1 were significantly higher in cancer tissues than benign nodules. Gene fusions were detected in 16 samples (2 at the DNA level and 14 at the RNA level). ATM mutation (ATMMUT) was frequently accompanied by BRAFMUT, TERTMUT or gene fusions. ATMMUT alone or ATM co-mutations were significantly positively correlated with lymph node metastasis. Accordingly, ATM knock-down PTC cells bearing BRAFV600E, KRASG12R or CCDC6-RET had higher proliferative ability and more aggressive potency than cells without ATM knock-down in vitro. Furthermore, combining gene alterations and clinical features significantly improved the predictive efficacy for lymph node metastasis of radiomic features, from 71.5 to 87.0%. CONCLUSIONS: Targeted sequencing of comprehensive genetic alterations in PTC has high prognostic value. These alterations, in combination with clinical and radiomic features, may aid in predicting invasive PTC with higher accuracy.


Asunto(s)
Metástasis Linfática , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Humanos , Metástasis Linfática/diagnóstico por imagen , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/patología , Cáncer Papilar Tiroideo/diagnóstico por imagen , Masculino , Femenino , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/diagnóstico por imagen , Persona de Mediana Edad , Mutación , Adulto , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas de la Ataxia Telangiectasia Mutada/genética , Nomogramas , Biomarcadores de Tumor/genética , Telomerasa/genética , Radiómica
8.
Nat Med ; 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38839897

RESUMEN

Gene therapy is a promising approach for hereditary deafness. We recently showed that unilateral AAV1-hOTOF gene therapy with dual adeno-associated virus (AAV) serotype 1 carrying human OTOF transgene is safe and associated with functional improvements in patients with autosomal recessive deafness 9 (DFNB9). The protocol was subsequently amended and approved to allow bilateral gene therapy administration. Here we report an interim analysis of the single-arm trial investigating the safety and efficacy of binaural therapy in five pediatric patients with DFNB9. The primary endpoint was dose-limiting toxicity at 6 weeks, and the secondary endpoint included safety (adverse events) and efficacy (auditory function and speech perception). No dose-limiting toxicity or serious adverse event occurred. A total of 36 adverse events occurred. The most common adverse events were increased lymphocyte counts (6 out of 36) and increased cholesterol levels (6 out of 36). All patients had bilateral hearing restoration. The average auditory brainstem response threshold in the right (left) ear was >95 dB (>95 dB) in all patients at baseline, and the average auditory brainstem response threshold in the right (left) ear was restored to 58 dB (58 dB) in patient 1, 75 dB (85 dB) in patient 2, 55 dB (50 dB) in patient 3 at 26 weeks, and 75 dB (78 dB) in patient 4 and 63 dB (63 dB) in patient 5 at 13 weeks. The speech perception and the capability of sound source localization were restored in all five patients. These results provide preliminary insights on the safety and efficacy of binaural AAV gene therapy for hereditary deafness. The trial is ongoing with longer follow-up to confirm the safety and efficacy findings. Chinese Clinical Trial Registry registration: ChiCTR2200063181 .

9.
Mikrochim Acta ; 191(7): 370, 2024 06 05.
Artículo en Inglés | MEDLINE | ID: mdl-38837084

RESUMEN

The development of an ultrasensitive and precise measurement of a breast cancer biomarker (cancer antigen 15-3; CA15-3) in complex human serum is essential for the early diagnosis of cancer in groups of healthy populations and the treatment of patients. However, currently available testing technologies suffer from insufficient sensitivity toward CA15-3, which severely limits early large-scale screening of breast cancer patients. We report a versatile electrochemical immunoassay method based on atomically cobalt-dispersed nitrogen-doped carbon (Co-NC)-modified disposable screen-printed carbon electrode (SPCE) with alkaline phosphatase (ALP) and its metabolite, ascorbic acid 2-phosphate (AAP), as the electrochemical labeling and redox signaling unit for sensitive detection of low-abundance CA15-3. During electrochemical detection by differential pulse voltammetry (DPV), it was found that the Co-NC-SPCE electrode did not have a current signal response to the AAP substrate; however, it had an extremely favorable response current to ascorbic acid (AA). Based on the above principle, the target CA15-3-triggered immunoassay enriched ALP-catalyzed AAP produces a large amount of AA, resulting in a significant change in the system current signal, thereby realizing the highly sensitive detection of CA15-3. Under the optimal AAP substrate concentration and ALP catalysis time, the Co-NC-SPCE-based electrochemical immunoassay demonstrated a good DPV current for CA15-3 in the assay interval of 1.0 mU/mL to 10,000 mU/mL, with a calculated limit of detection of 0.38 mU/mL. Since Co-NC-SPCE has an excellent DPV current response to AA and employs split-type scheme, the constructed electrochemical immunoassay has the merits of high preciseness and anti-interference, and its clinical diagnostic results are comparable to those of commercial kits.


Asunto(s)
Ácido Ascórbico , Biomarcadores de Tumor , Neoplasias de la Mama , Carbono , Cobalto , Técnicas Electroquímicas , Mucina-1 , Nitrógeno , Humanos , Inmunoensayo/métodos , Neoplasias de la Mama/sangre , Mucina-1/sangre , Biomarcadores de Tumor/sangre , Técnicas Electroquímicas/métodos , Carbono/química , Nitrógeno/química , Cobalto/química , Ácido Ascórbico/química , Ácido Ascórbico/sangre , Ácido Ascórbico/análogos & derivados , Femenino , Límite de Detección , Fosfatasa Alcalina/sangre , Fosfatasa Alcalina/química , Electrodos , Técnicas Biosensibles/métodos
10.
Theranostics ; 14(8): 3317-3338, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38855188

RESUMEN

Metastasis is one of the key factors of treatment failure in late-stage colorectal cancer (CRC). Metastatic CRC frequently develops resistance to chemotherapeutic agents. This study aimed to identify the novel regulators from "hidden" proteins encoded by long noncoding RNAs (lncRNAs) involved in tumor metastasis and chemoresistance. Methods: CRISPR/Cas9 library functional screening was employed to identify the critical suppressor of cancer metastasis in highly invasive CRC models. Western blotting, immunofluorescence staining, invasion, migration, wound healing, WST-1, colony formation, gain- and loss-of-function experiments, in vivo experimental metastasis models, multiplex immunohistochemical staining, immunohistochemistry, qRT-PCR, and RT-PCR were used to assess the functional and clinical significance of FOXP3, PRDM16-DT, HNRNPA2B1, and L-CHEK2. RNA-sequencing, co-immunoprecipitation, qRT-PCR, RT-PCR, RNA affinity purification, RNA immunoprecipitation, MeRIP-quantitative PCR, fluorescence in situ hybridization, chromatin immunoprecipitation and luciferase reporter assay were performed to gain mechanistic insights into the role of PRDM16-DT in cancer metastasis and chemoresistance. An oxaliplatin-resistant CRC cell line was established by in vivo selection. WST-1, colony formation, invasion, migration, Biacore technology, gain- and loss-of-function experiments and an in vivo experimental metastasis model were used to determine the function and mechanism of cimicifugoside H-1 in CRC. Results: The novel protein PRDM16-DT, encoded by LINC00982, was identified as a cancer metastasis and chemoresistance suppressor. The down-regulated level of PRDM16-DT was positively associated with malignant phenotypes and poor prognosis of CRC patients. Transcriptionally regulated by FOXP3, PRDM16-DT directly interacted with HNRNPA2B1 and competitively decreased HNRNPA2B1 binding to exon 9 of CHEK2, resulting in the formation of long CHEK2 (L-CHEK2), subsequently promoting E-cadherin secretion. PRDM16-DT-induced E-cadherin secretion inhibited fibroblast activation, which in turn suppressed CRC metastasis by decreasing MMP9 secretion. Cimicifugoside H-1, a natural compound, can bind to LEU89, HIS91, and LEU92 of FOXP3 and significantly upregulated PRDM16-DT expression to repress CRC metastasis and reverse oxaliplatin resistance. Conclusions: lncRNA LINC00982 can express a new protein PRDM16-DT to function as a novel regulator in cancer metastasis and drug resistance of CRC. Cimicifugoside H-1 can act on the upstream of the PRDM16-DT signaling pathway to alleviate cancer chemoresistance.


Asunto(s)
Neoplasias Colorrectales , Proteínas de Unión al ADN , Resistencia a Antineoplásicos , Regulación Neoplásica de la Expresión Génica , Metástasis de la Neoplasia , ARN Largo no Codificante , Factores de Transcripción , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Humanos , Resistencia a Antineoplásicos/genética , Animales , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Ratones , Línea Celular Tumoral , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Ribonucleoproteína Heterogénea-Nuclear Grupo A-B/metabolismo , Ribonucleoproteína Heterogénea-Nuclear Grupo A-B/genética , Oxaliplatino/farmacología , Oxaliplatino/uso terapéutico , Empalme del ARN/genética , Movimiento Celular/efectos de los fármacos , Ratones Desnudos , Ratones Endogámicos BALB C
11.
Stem Cell Res ; 79: 103479, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38908299

RESUMEN

Diamond-Blackfan anemia syndrome (DBAS) is an inherited bone marrow failure disorder that typically presents in infancy as hypoplastic anemia and developmental abnormalities in approximately 50% of cases. DBAS is caused by haploinsufficiency in one of 24 ribosomal protein genes, with RPS19 mutations accounting for 25% of cases. We generated iPSC lines from two patients with different heterozygous RPS19 mutations (c.191T > C and c.184C > T) and isogenic lines in which the mutations were corrected by Cas9-mediated homology directed repair.

12.
Fundam Res ; 4(1): 103-112, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38933835

RESUMEN

Oceanic uptake and storage of anthropogenic CO2 (CANT) are regulated by ocean circulation and ventilation. To decipher the storage and redistribution of CANT in the western North Pacific, where a major CANT sink develops, we investigated the water column carbonate system, dissolved inorganic radiocarbon and ancillary parameters in May and August 2018, spanning the Kuroshio Extension (KE, 35-39 °N), Kuroshio Recirculation (KR, 27-35 °N) and subtropical (21-27 °N) zones. Water column CANT inventories were estimated to be 40.5 ± 1.1 mol m-2 in the KR zone and 37.2 ± 0.9 mol m-2 in the subtropical zone. In comparison with historical data obtained in 2005, relatively high rates of increase of the CANT inventory of 1.05 ± 0.20 and 1.03 ± 0.12 mol m-2 yr-1 in the recent decade were obtained in the KR and subtropical zones, respectively. Our water-mass-based analyses suggest that formation and transport of subtropical mode water dominate the deep penetration, storage, and redistribution of CANT in those two regions. In the KE zone, however, both the water column CANT inventory and the decadal CANT accumulation rate were small and uncertain owing to the dynamic hydrology, where the naturally uplifting isopycnal surfaces make CANT penetration relatively shallow. The findings of this study improve the understanding of the spatiotemporal variations of CANT distribution, storage, and transport in the western North Pacific.

13.
Biomed Environ Sci ; 37(4): 354-366, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38727158

RESUMEN

Objective: This study investigated the impact of occupational mercury (Hg) exposure on human gene transcription and expression, and its potential biological mechanisms. Methods: Differentially expressed genes related to Hg exposure were identified and validated using gene expression microarray analysis and extended validation. Hg-exposed cell models and PTEN low-expression models were established in vitro using 293T cells. PTEN gene expression was assessed using qRT-PCR, and Western blotting was used to measure PTEN, AKT, and PI3K protein levels. IL-6 expression was determined by ELISA. Results: Combined findings from gene expression microarray analysis, bioinformatics, and population expansion validation indicated significant downregulation of the PTEN gene in the high-concentration Hg exposure group. In the Hg-exposed cell model (25 and 10 µmol/L), a significant decrease in PTEN expression was observed, accompanied by a significant increase in PI3K, AKT, and IL-6 expression. Similarly, a low-expression cell model demonstrated that PTEN gene knockdown led to a significant decrease in PTEN protein expression and a substantial increase in PI3K, AKT, and IL-6 levels. Conclusion: This is the first study to report that Hg exposure downregulates the PTEN gene, activates the PI3K/AKT regulatory pathway, and increases the expression of inflammatory factors, ultimately resulting in kidney inflammation.


Asunto(s)
Inflamación , Mercurio , Fosfohidrolasa PTEN , Humanos , Regulación hacia Abajo , Células HEK293 , Inflamación/inducido químicamente , Inflamación/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-6/sangre , Mercurio/toxicidad , Exposición Profesional/efectos adversos , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Transducción de Señal/efectos de los fármacos
14.
Aging (Albany NY) ; 16(10): 8880-8897, 2024 05 17.
Artículo en Inglés | MEDLINE | ID: mdl-38761176

RESUMEN

OBJECTIVE: This inquiry endeavors to delineate the influence of PDIA3 on tumor-associated macrophages within the realm of colorectal malignancies, whilst elucidating the intrinsic biochemical pathways. METHOD: Leveraging bioinformatics, we scrutinized the symbiosis between PDIA3, STAT3, and CD274. A xenograft model in immunodeficient murine served to assess PDIA3's impact on colorectal carcinogenesis. Further, Western blot analysis quantified the protein expression of PDIA3, p-STAT3, PD-1, XBP-1, assorted enzymes, and IL-6. Moreover, in vitro assays gauged SW480 cellular dynamics inclusive of migration, invasive potential, and proliferation. RESULTS: Bioinformatics exploration exposed PDIA3's elevated presence in diverse cancers, with a marked expression in colorectal cancer, as per TCGA and GEO repositories. Correlative studies showed PDIA3 positively aligning with STAT3 and CD274, the latter also associated with monocyte-derived macrophages. Comparative analysis of colorectal neoplasms and normal colon samples unveiled heightened levels of PDIA3 markers which, when overexpressed in SW480 cells, escalated tumorigenicity and oncogenic behaviors, with a noted decrease upon PD-1 monoclonal antibody intervention. CONCLUSIONS: PDIA3 augments the M2 polarization of tumor-associated macrophages via modulation of the STAT3/PD-1 cascade, thus invigorating the tumorous proliferation and dissemination in colorectal cancer. Such revelations position PDIA3 as an auspicious target for PD-1 blockade therapeutics, offering a promising foundation for rectifying colorectal carcinoma.


Asunto(s)
Neoplasias Colorrectales , Receptor de Muerte Celular Programada 1 , Proteína Disulfuro Isomerasas , Factor de Transcripción STAT3 , Transducción de Señal , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/genética , Humanos , Animales , Ratones , Proteína Disulfuro Isomerasas/metabolismo , Proteína Disulfuro Isomerasas/genética , Receptor de Muerte Celular Programada 1/metabolismo , Receptor de Muerte Celular Programada 1/genética , Línea Celular Tumoral , Progresión de la Enfermedad , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/inmunología , Proliferación Celular , Macrófagos/metabolismo
15.
Phytomedicine ; 130: 155733, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-38759314

RESUMEN

BACKGROUND: The proinflammatory response induced by macrophages plays a crucial role in the development of sepsis and the resulting multiorgan dysfunction. Identifying new regulatory targets for macrophage homeostasis and devising effective treatment strategies remains a significant challenge in contemporary research. PURPOSE: This study aims to identify new regulatory targets for macrophage homeostasis and develop effective strategies for treating sepsis. STUDY DESIGN AND METHODS: Macrophage infiltration in septic patients and in lungs, kidneys, and brains of caecum ligation and puncture (CLP)-induced septic mice was observed using CIBERSORT and immunofluorescence (IF). Upon integrating the MSigDB database and GSE65682 dataset, differently expressed macrophage-associated genes (DEMAGs) were identified. Critical DEMAGs were confirmed through machine learning. The protein level of the critical DEMAG was detected in PBMCs of septic patients, RAW264.7 cells, and mice lungs, kidneys, and brains using ELISA, western blot, immunohistochemistry, and IF. siRNA was applied to investigate the effect of the critical DEMAG in RAW264.7 cells. A natural product library was screened to find a compound targeting the critical DEMAG protein. The binding of compounds and proteins was analyzed through molecular docking, molecular dynamics simulations, CETSA, and MST analysis. The therapeutic efficacy of the compounds against sepsis was then evaluated through in vitro and in vivo experiments. RESULTS: Macrophage infiltration was inversely correlated with survival in septic patients. The critical differentially expressed molecule RasGRP1 was frequently observed in the PBMCs of septic patients, LPS-induced RAW264.7 cells, and the lungs, kidneys, and brains of septic mice. Silencing RasGRP1 alleviated proinflammatory response and oxidative stress in LPS-treated RAW264.7 cells. Catechin Hydrate (CH) was identified as an inhibitor of RasGRP1, capable of maintaining macrophage homeostasis and mitigating lung, kidney, and brain damage during sepsis. CONCLUSION: This study demonstrates that RasGRP1, a novel activator of macrophage proinflammatory responses, plays a crucial role in the excessive inflammation and oxidative stress associated with sepsis. CH shows potential for treating sepsis by inhibiting RasGRP1.


Asunto(s)
Catequina , Factores de Intercambio de Guanina Nucleótido , Macrófagos , Sepsis , Animales , Sepsis/tratamiento farmacológico , Ratones , Humanos , Células RAW 264.7 , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Factores de Intercambio de Guanina Nucleótido/metabolismo , Catequina/farmacología , Insuficiencia Multiorgánica/tratamiento farmacológico , Simulación del Acoplamiento Molecular , Riñón/efectos de los fármacos , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Pulmón/efectos de los fármacos
16.
PeerJ ; 12: e17381, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38726379

RESUMEN

Background: Escherichia coli is an important intestinal flora, of which pathogenic E. coli is capable of causing many enteric and extra-intestinal diseases. Antibiotics are essential for the treatment of bacterial infections caused by pathogenic E. coli; however, with the widespread use of antibiotics, drug resistance in E. coli has become particularly serious, posing a global threat to human, animal, and environmental health. While the drug resistance and pathogenicity of E. coli carried by tigers and leopards in captivity have been studied intensively in recent years, there is an extreme lack of information on E. coli in these top predators in the wild environment. Methods: Whole genome sequencing data of 32 E. coli strains collected from the feces of wild Amur tiger (Panthera tigris altaica, n = 24) and North China leopard (Panthera pardus japonensis, n = 8) were analyzed in this article. The multi-locus sequence types, serotypes, virulence and resistance genotypes, plasmid replicon types, and core genomic SNPs phylogeny of these isolates were studied. Additionally, antimicrobial susceptibility testing (AST) was performed on these E. coli isolates. Results: Among the E. coli isolates studied, 18 different sequence types were identified, with ST939 (21.9%), ST10 (15.6%), and ST3246 (9.4%) being the most prevalent. A total of 111 virulence genes were detected, averaging about 54 virulence genes per sample. They contribute to invasion, adherence, immune evasion, efflux pump, toxin, motility, stress adaption, and other virulence-related functions of E. coli. Sixty-eight AMR genes and point mutations were identified. Among the detected resistance genes, those belonging to the efflux pump family were the most abundant. Thirty-two E. coli isolates showed the highest rate of resistance to tetracycline (14/32; 43.8%), followed by imipenem (4/32; 12.5%), ciprofloxacin (3/32; 9.4%), doxycycline (2/32; 6.3%), and norfloxacin (1/32; 3.1%). Conclusions: Our results suggest that E. coli isolates carried by wild Amur tigers and North China leopards have potential pathogenicity and drug resistance.


Asunto(s)
Escherichia coli , Heces , Panthera , Tigres , Secuenciación Completa del Genoma , Animales , Tigres/microbiología , Escherichia coli/genética , Escherichia coli/efectos de los fármacos , Escherichia coli/patogenicidad , Escherichia coli/aislamiento & purificación , Panthera/microbiología , Heces/microbiología , Infecciones por Escherichia coli/veterinaria , Infecciones por Escherichia coli/microbiología , Filogenia , Antibacterianos/farmacología , Genoma Bacteriano/genética , Pruebas de Sensibilidad Microbiana , China , Virulencia/genética , Farmacorresistencia Bacteriana/genética , Polimorfismo de Nucleótido Simple/genética , Tipificación de Secuencias Multilocus
17.
Nat Commun ; 15(1): 4270, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38769299

RESUMEN

Néel spin-orbit torque allows a charge current pulse to efficiently manipulate the Néel vector in antiferromagnets, which offers a unique opportunity for ultrahigh density information storage with high speed. However, the reciprocal process of Néel spin-orbit torque, the generation of ultrafast charge current in antiferromagnets has not been demonstrated. Here, we show the experimental observation of charge current generation in antiferromagnetic metallic Mn2Au thin films using ultrafast optical excitation. The ultrafast laser pulse excites antiferromagnetic magnons, resulting in instantaneous non-equilibrium spin polarization at the antiferromagnetic spin sublattices with broken spatial symmetry. Then the charge current is generated directly via spin-orbit fields at the two sublattices, which is termed as the reciprocal phenomenon of Néel spin-orbit torque, and the associated THz emission can be detected at room temperature. Besides the fundamental significance on the Onsager reciprocity, the observed magnonic charge current generation in antiferromagnet would advance the development of antiferromagnetic THz emitter.

18.
Sci Rep ; 14(1): 12281, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38811638

RESUMEN

A large number of economic forests, especially apple orchards (AOs) in the Loess Plateau region of China, have been planted to develop the local economy and increase the income of farmers. The two main constraints preventing AOs on the Loess Plateau from developing sustainably and producing a high and steady yield are soil moisture content (SMC) and soil organic carbon (SOC). Nevertheless, little is currently known about the contributions of roots to these changes in the soil profile and the temporal modes of the SMC-SOC coupled effects. In our research, we analyzed the dynamic changes in SMC and SOC in AOs of various years in northern Shaanxi Province, as well as the coupled relationship between the two, and attempted to describe the function of roots in these changes. Research have shown: (1) As the age of the AOs increased, the SMC continued to decline throughout the 0-500 cm profile, especially at depths of 100-500 cm. SMC depletion mainly occurred in AOs aged 20 years (30.02%/year) and 30 years (31.18%/year). (2) Compared with abandoned land (AL), all the AOs except for the 6-year-old AO showed a carbon sequestration effect, and the carbon sequestration effect increased with age. The carbon sequestration rate of the 12-year-old AO was the highest and then decreased with age. Both surface and deeper soils showed better carbon sequestration, with a large amount of SOC being sequestered in deeper soil layers (> 100 cm). (3) The coupled effects of SMC and SOC varied with age and depth. The SMC in the deeper layers was significantly negatively correlated with SOC. Root dry weight density (RDWD) was significantly negatively correlated with SMC and significantly positively correlated with SOC. Path analysis suggested that SMC directly affects SOC at different soil depths, and regulates SOC by affecting RDWD, but these effects are significantly different at different depths. Therefore, we propose that management of AO should focus on the moisture deficit and carbon sequestration capabilities of deeper soils to ensure the sustainability of water use in AOs and the stability of agricultural carbon sequestration on the Loess Plateau.

19.
Mol Ther Nucleic Acids ; 35(2): 102207, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38800558
20.
Analyst ; 149(13): 3585-3595, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38767148

RESUMEN

The main protease of SARS-CoV-2 (SARS-CoV-2 Mpro) plays a critical role in the replication and life cycle of the virus. Currently, how to screen SARS-CoV-2 Mpro inhibitors from complex traditional Chinese medicine (TCM) is the bottleneck for exploring the pharmacodynamic substances of TCM against SARS-CoV-2. In this study, a simple, cost-effective, rapid, and selective fluorescent sensor (TPE-S-TLG sensor) was designed with an AIE (aggregation-induced emission) probe (TPE-Ph-In) and the SARS-CoV-2 Mpro substrate (S-TLG). The TPE-S-TLG sensor was characterized using UV-Vis absorption spectroscopy, fluorescence spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM), zeta potential, and Fourier transform infrared (FTIR) spectroscopy techniques. The limit of detection of this method to detect SARS-CoV-2 Mpro was measured to be 5 ng mL-1. Furthermore, the TPE-S-TLG sensor was also successfully applied to screen Mpro inhibitors from Xuebijing injection using the separation and collection of the HPLC-fully automatic partial fraction collector (HPLC-FC). Six active compounds, including protocatechualdehyde, chlorogenic acid, hydroxysafflower yellow A, caffeic acid, isoquercetin, and pentagalloylglucose, were identified using UHPLC-Q-TOF/MS that could achieve 90% of the Mpro inhibition rate for the Xuebijing injection. Accordingly, the strategy can be broadly applied in the detection of disease-related proteases as well as screening active substances from TCM.


Asunto(s)
Proteasas 3C de Coronavirus , Colorantes Fluorescentes , Medicina Tradicional China , SARS-CoV-2 , Espectrometría de Fluorescencia , SARS-CoV-2/aislamiento & purificación , SARS-CoV-2/efectos de los fármacos , Proteasas 3C de Coronavirus/antagonistas & inhibidores , Proteasas 3C de Coronavirus/metabolismo , Humanos , Colorantes Fluorescentes/química , Espectrometría de Fluorescencia/métodos , Antivirales/farmacología , Antivirales/análisis , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/análisis , COVID-19/virología , COVID-19/diagnóstico , Límite de Detección , Tratamiento Farmacológico de COVID-19
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