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The elders in China's rural areas are facing challenges in maintaining agricultural production due to the outflow of rural laborers. The Transfer of land could alleviate the burden of land-based livelihoods for rural elders, but their decisions regarding land transfer are influenced by their social networks within the context of Chinese rural society. This study investigates how social networks impact the willingness of rural elders to transfer land. Using survey data from 782 rural elders in 32 villages across 11 provinces in China, this paper applies multilinear and binary logistic regression models. The results indicate that the willingness of rural elders to transfer land is affected by their social neteork: (1) Internal network scale, network heterogeneity, and frequency of external network relationships have a significantly positive influence on rural elders' willingness to transfer land, while frequency of internal network relationships has a significantly negative influence. (2) There are group differences in the above impacts, and these significant impacts occur only among male elderly individuals aged 60-69 years old or living in central and western regions. (3) Social networks primarily influence rural elders' willingness to transfer land through three mechanisms: information consultation, interpersonal trust, and material resource acquisition. A larger internal social network scale, higher heterogeneity within the network, and more frequent interactions with members of external networks lead to greater access to useful information, higher levels of trust in others, increased material resources availability, and an increased likelihood of transferring land. These findings can inform government policies aimed at improving practices related to land transfers and old age security for rural elders.
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Skeletal muscle aging in rats is a reduction in skeletal muscle mass caused by a decrease in the number or volume of skeletal muscle myofibers. Apoptosis has been recognized to play a key role in accelerating the process of skeletal muscle aging in rats. The thioredoxin (Trx) system is a widely expressed oxidoreductase system that controls the cellular reduction/oxidation state and has both potent anti-free radical damage and important pro-growth and apoptosis inhibitory functions. Previous studies have shown that exercise delays skeletal muscle aging. However, it is unclear whether exercise attenuates skeletal muscle aging via the Trx system. Therefore, the present study used the Trx system as an entry point to explore the effect of aerobic exercise to improve skeletal muscle aging in rats and its possible mechanisms, and to provide a theoretical basis for exercise to delay skeletal muscle aging in rats. It was shown that aerobic exercise in senescent rats resulted in increased gastrocnemius index, decreased body weight, increased endurance, decreased skeletal muscle cell apoptosis, increased activity and protein expression of the Trx system, and decreased expression of p38 and ASK1. Based on these findings, we conclude that 10 weeks of aerobic exercise may enhance the anti-apoptotic effect of Trx by up-regulating Trx and Trx reductase (TR) protein expression, which in turn increases Trx activity in rat skeletal muscle, and ultimately alleviates apoptosis in senescent skeletal muscle cells.
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Envejecimiento , Apoptosis , Músculo Esquelético , Condicionamiento Físico Animal , Tiorredoxinas , Animales , Músculo Esquelético/fisiología , Músculo Esquelético/metabolismo , Masculino , Tiorredoxinas/metabolismo , Condicionamiento Físico Animal/fisiología , Envejecimiento/fisiología , Ratas , MAP Quinasa Quinasa Quinasa 5/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Ratas Sprague-Dawley , Reductasa de Tiorredoxina-Disulfuro/metabolismo , Resistencia Física/fisiologíaRESUMEN
BACKGROUND: Previous studies have identified a diverse group of microbial taxa that differ between patients with multiple sclerosis (MS) and the healthy population. However, interpreting findings on MS-associated microbiota is challenging, as there is no true consensus. It is unclear whether there is gut microbiota commonly altered in MS across studies. METHODS: To answer this, we performed a meta-analysis based on the 16S rRNA gene sequencing data from seven geographically and technically diverse studies comprising a total of 524 adult subjects (257 MS and 267 healthy controls). Analysis was conducted for each individual study after reprocessing the data and also by combining all data together. The blocked Wilcoxon rank-sum test and linear mixed-effects regression were used to identify differences in microbial composition and diversity between MS and healthy controls. Network analysis was conducted to identify bacterial correlations. A leave-one-out sensitivity analysis was performed to ensure the robustness of the findings. RESULTS: The microbiome community structure was significantly different between studies. Re-analysis of data from individual studies revealed a lower relative abundance of Prevotella in MS across studies, compared to controls. Meta-analysis found that although alpha and beta diversity did not differ between MS and controls, a higher abundance of Actinomyces and a lower abundance of Faecalibacterium were reproducibly associated with MS. Additionally, network analysis revealed that the recognized negative Bacteroides-Prevotella correlation in controls was disrupted in patients with MS. CONCLUSIONS: Our meta-analysis identified common gut microbiota associated with MS across geographically and technically diverse studies.
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Microbioma Gastrointestinal , Esclerosis Múltiple , ARN Ribosómico 16S , Humanos , Esclerosis Múltiple/microbiología , Microbioma Gastrointestinal/genética , ARN Ribosómico 16S/genética , Bacterias/genética , Bacterias/clasificación , Adulto , Masculino , Femenino , Estudios de Casos y ControlesRESUMEN
Nonsense-mediated mRNA decay (NMD) is an important RNA quality control pathway. It aids in degrading harmful erroneous mRNA, thereby preserving a stable and healthy internal environment. In this study, we employed CRISPR/Cas9 and amiRNA technology to generate knock out or knock down mutants of realted genes in the rice NMD pathway. Through transcriptome sequencing and observing phenotype changes, the study explored the impact of NMD pathway defects on rice gene expression and alternative splicing. The results suggest that even partial defects will induce phenotypic changes such as plant height and pollen vitality to different degrees, showing necessity of NMD factors. Gene expression analysis reveals that most differentially expressed genes are upregulated in the mutants, with ko-upf1-like and kd-upf1 defects having a more significant impact than kd-upf2 and kd-upf3. Specifically, NMD pathway defects result in increased expression levels of rice defense response-related genes and decreased expression levels of secondary metabolism-related genes, with a wider range of affected genes observed in 60-day-old senescence mutants. Transcript analysis indicates that different NMD related genes defects alter hundreds of alternative splicing events, mostly enriched in genes involving alternative splicing regulatory pathways. Approximately half of these events are shared among different mutants, and a substantial number of affected transcripts show NMD target features. NMD could affect both the transcript abundance and their splicing subtypes to regulate the defense response and early-senescence associated pathways, which plays a vital role in rice growth and reproduction.
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Regulación de la Expresión Génica de las Plantas , Degradación de ARNm Mediada por Codón sin Sentido , Oryza , Fenotipo , Transcriptoma , Oryza/genética , Oryza/crecimiento & desarrollo , Oryza/metabolismo , Degradación de ARNm Mediada por Codón sin Sentido/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Empalme AlternativoRESUMEN
Basalt fiber (BF) with modification of iron (Fe-MBF) and calcium (Ca-MBF) were filled into constructed wetland-microbial fuel cell (CW-MFC) for innovative comparison of improved performance under perfluorooctanoic acid (PFOA) exposure. More enhancement on nitrogen and phosphorus removal was observed by Fe-MBF than Ca-MBF, with significant increase of ammonium (NH4+-N) removal by 3.36-5.66 % (p < 0.05) compared to control, even under PFOA stress. Markedly higher removal efficiency of PFOA by 4.76-8.75 % (p < 0.05) resulted from Fe-MBF, compared to Ca-MBF and control BF groups. Besides, superior electrochemical performance was found in Fe-MBF group, with maximum power density 28.65 % higher than control. Fe-MBF caused higher abundance of dominant microbes on electrodes ranged from phylum to family. Meanwhile, ammonia oxidizing bacteria like Nitrosomonas was more abundant in Fe-MBF group, which was positively correlated to NH4+-N and total nitrogen removal. Some other functional genera involved in denitrification and phosphorus-accumulation were enriched by Fe-MBF on electrodes and MBF carrier, including Dechloromonas, Candidatus_Competibacter, and Pseudomonas. Additionally, there were more biomarkers in Fe-MBF group, like Pseudarcobacter and Acidovorax, conducive to nitrogen and iron cycling. Most functional genes of nitrogen, carbon, and sulfur metabolisms were up-regulated with Fe-MBF filling, causing improvement on nitrogen removal.
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Bacterias , Fuentes de Energía Bioeléctrica , Fósforo , Humedales , Bacterias/metabolismo , Bacterias/genética , Fósforo/química , Nitrógeno , Contaminantes Químicos del Agua/toxicidad , Hierro/química , Caprilatos , Calcio/metabolismoRESUMEN
BACKGROUND: The role of miR-145-5p in non-small cell lung cancer (NSCLC) has been studied, however, the regulation of hBMSCs-derived exosomes (Exo) transmitted miR-145-5p in NSCLC was still unknown. This study aimed to investigate the role of hBMSCs-derived exosomes (Exo) in the progression of NSCLC. METHODS: The Exo was extracted from hBMSCs and added to A549 and H1299 cell culture, followed by the detection of cell proliferation, migration, and invasion. The correlation between the expression of miR-145-5p and SOX9, as well as their binding relationship was determined by correlation analysis, luciferase gene reporter assay and RNA pull-down assays. The in vivo animal model was established to further verify the impact of hBMSCs-Exo. RESULTS: It showed that miR-145-5p was downregulated and SOX9 was upregulated in NSCLC tissues. HBMSCs-derived Exo, and hBMSCs-Exo with overexpression of miR-145-5p could inhibit cell proliferation, migration, and invasion of both A549 and H1299 cells, and prevent against tumor progression in vivo. MiR-145-5p and SOX9 were found to be able to bind to each other, and a negative correlation were observed between the expression of them in NSCLC tissues. Furthermore, inhibition of SOX9 could reversed the suppressed role of miR-145-5p in vitro and in vivo. CONCLUSION: Therefore, HBMSCs-Exo effectively transmitted miR-145-5p, leading to the suppression of malignant development in NSCLC through the regulation of SOX9.
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Carcinoma de Pulmón de Células no Pequeñas , Movimiento Celular , Proliferación Celular , Exosomas , Neoplasias Pulmonares , Células Madre Mesenquimatosas , MicroARNs , Factor de Transcripción SOX9 , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Factor de Transcripción SOX9/metabolismo , Factor de Transcripción SOX9/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Animales , Exosomas/metabolismo , Exosomas/genética , Ratones , Proliferación Celular/genética , Células Madre Mesenquimatosas/metabolismo , Movimiento Celular/genética , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral , Masculino , Femenino , Células A549 , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Microplastics (MPs) are increasingly becoming recognized as worldwide environmental contaminants, exerting a substantial impact on the safety of city rivers. This study explored the abundance and characteristics of MPs in summer 2023, including June and August, representing plum rain and typhoon rain seasons. The Qinhuai River exhibits more spatial fluctuations in six sampling sites with average concentrations of 470 ± 119.56 items per L, and the abundance increases with the water flows in the river. Downstream had the highest MP abundance of 484 ± 121.34 items per L, which were positive with the concentration of suspended solids (SS). Transparent and green MPs were more even in the sampling sites, and the shapes of fragments were predominant in the summer. Interestingly, the proportion of fiber and small-sized (38-75 µm) microplastics was predominant in the plum rain seasons, while the percentage of large-sized (270-5000 µm) and polymers of PE occurred in the typhoon rain seasons. The index of hazard scores of plastic polymers (H) revealed that the studied river had a severe pollution level (IV), which was highly influenced by PVC and PC. Besides, the pollution load index PLI value of different rain seasons was slightly polluted (I), while the PLI in autumn rain seasons was relatively higher than that in other seasons due to the higher variance of MPs. Therefore, the ecological risk of microplastics of PVC and PC in the Qinhuai River during varying seasons should be seriously considered. Our research is expected to provide valuable assistance in improving the management of urban rivers.
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Monitoreo del Ambiente , Microplásticos , Ríos , Estaciones del Año , Contaminantes Químicos del Agua , China , Ríos/química , Microplásticos/análisis , Contaminantes Químicos del Agua/análisis , Medición de Riesgo , CiudadesRESUMEN
3D carbon-based porous sponges are recognized for significant potential in oil absorption and electromagnetic interference (EMI). However, their widespread application is hindered by a common compromise between high performance and affordability of mass production. Herein, a novel approach is introduced that involves laser-assisted micro-zone heating melt-blown spinning (LMHMS) to address this challenge by creating pitch-based submicron carbon fibers (PSCFs) sponge with 3D interconnected structures. These structures bestow the resulting sponge exceptional characteristics including low density (≈20 mg cm-3), high porosity (≈99%), remarkable compressibility (80% maximum strain), and superior conductivity (≈628 S m-1). The resultant PSCF sponges realize an oil/organic solvent sorption capacity over 56 g/g and possess remarkable regenerated ability. In addition to their effectiveness in cleaning up oil/organic solvent spills, they also demonstrated strong electromagnetic shielding capabilities, with a total shielding effectiveness (SE) exceeding 60 dB across the X-band GHz range. In virtue of extreme lightweight of ≈20 mg cm-3, the specific SE of the PSCF sponge reaches as high as ≈1466 dB cm3 g-1, surpassing the performance of numerous carbon-based porous structures. Thus, the unique blend of properties renders these sponges promising for transforming strategies in addressing oil/organic solvent contaminations and providing effective protection against EMI.
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Centromeres in most multicellular eukaryotes are composed of long arrays of repetitive DNA sequences. Interestingly, several transposable elements, including the well-known long terminal repeat centromeric retrotransposon of maize (CRM), were found to be enriched in functional centromeres marked by the centromeric histone H3 (CENH3). Here, we report a centromeric long interspersed nuclear element (LINE), Celine, in Populus species. Celine has colonized preferentially in the CENH3-associated chromatin of every poplar chromosome, with 84% of the Celine elements localized in the CENH3-binding domains. In contrast, only 51% of the CRM elements were bound to CENH3 domains in Populus trichocarpa. These results suggest different centromere targeting mechanisms employed by Celine and CRM elements. Nevertheless, the high target specificity seems to be detrimental to further amplification of the Celine elements, leading to a shorter life span and patchy distribution among plant species compared with the CRM elements. Using a phylogenetically guided approach, we were able to identify Celine-like LINE elements in tea plant (Camellia sinensis) and green ash tree (Fraxinus pennsylvanica). The centromeric localization of these Celine-like LINEs was confirmed in both species. We demonstrate that the centromere targeting property of Celine-like LINEs is of primitive origin and has been conserved among distantly related plant species.
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Centrómero , Cromosomas de las Plantas , Populus , Retroelementos , Populus/genética , Centrómero/genética , Centrómero/metabolismo , Cromosomas de las Plantas/genética , Retroelementos/genética , Elementos de Nucleótido Esparcido Largo/genética , Filogenia , Histonas/metabolismo , Histonas/genéticaRESUMEN
BACKGROUND: Infections are commonly seen in wounds. The overall infection rate is 1.8% to 4.2%. Improper infection management can lead to serious conditions and may progress to life-threatening sepsis. Because there is a need for assistance in predicting wound infection before obvious clinical symptoms, the measurement of cytokines in wound tissue fluids has attracted our attention for determining the overall status of wound infection. Our intent was to assess the potential biomarkers in the diagnosis of wound infection. METHODS: We collected 146 tissue fluids (acute: 59, chronic: 61, and normal: 26) for analysis of biomarkers using a human cytokine array. Serum C-reactive protein was also measured from 104 patients. The sensitivity and specificity of significant wound cytokines and serum C-reactive protein for the diagnosis of wound infection were evaluated. RESULTS: Among biomarkers examined, serum C-reactive protein and tissue C-reactive protein were highly expressed in acute infection wounds, whereas monocyte chemoattractant protein-1 was significantly expressed in chronic infection wounds. Because the expression of wound biomarkers varied in different types of wounds, relationships among them were studied. A high correlation between tissue C-reactive protein and interleukin-8 (R2 = 0.7) and a moderate correlation between systemic and local C-reactive protein (R2 = 0.47) were observed. In addition, tissue monocyte chemoattractant protein-1 had better sensitivity (74%) and specificity (65%) in the diagnosis of wound infection. Moreover, combined serum C-reactive protein with monocyte chemoattractant protein-1 examination provided a higher area under the curve in the receiver operator characteristic curve (0.75). CONCLUSION: We found that tissue monocyte chemoattractant protein-1 is a superior diagnostic marker for assistance with the diagnosis of wound infection.
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Biomarcadores , Proteína C-Reactiva , Quimiocina CCL2 , Sensibilidad y Especificidad , Humanos , Quimiocina CCL2/análisis , Quimiocina CCL2/metabolismo , Quimiocina CCL2/sangre , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Biomarcadores/metabolismo , Biomarcadores/análisis , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Infección de Heridas/diagnóstico , Infección de Heridas/metabolismo , Anciano de 80 o más Años , Interleucina-8/análisis , Interleucina-8/metabolismo , Curva ROC , Líquidos Corporales/química , Líquidos Corporales/metabolismoRESUMEN
Alzheimer's disease (AD) and osteoarthritis (OA) are both senile degenerative diseases. Clinical studies have found that OA patients have a significantly increased risk of AD in their later life. This study hypothesized that chronic aseptic inflammation might lead to AD in KOA patients. However, current research has not yet clarified the potential mechanism between AD and KOA. Therefore, this study intends to use KOA transcriptional profiling and single-cell sequencing analysis technology to explore the molecular mechanism of KOA affecting AD development, and screen potential molecular biomarkers and drugs for the prediction, diagnosis, and prognosis of AD in KOA patients. It was found that the higher the expression of TXNIP, MMP3, and MMP13, the higher the risk coefficient of AD was. In addition, the AUC of TXNIP, MMP3, and MMP13 were all greater than 0.70, which had good diagnostic significance for AD. Finally, through the virtual screening of core proteins in FDA drugs and molecular dynamics simulation, it was found that compound Cobicistat could be targeted to TXNIP, Itc could be targeted to MMP3, and Isavuconazonium could be targeted to MMP13. To sum up, TXNIP, MMP3, and MMP13 are prospective molecular markers in KOA with AD, which could be used to predict, diagnose, and prognosis.
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In this study, ferrous ion (Fe(II)) had the potential to promote ecological functions in constructed wetlands (CWs) under perfluorooctanoic acid (PFOA) stress. Concretely, Fe(II) at 30 mg/L and 20-30 mg/L even led to 11.37% increase of urease and 93.15-243.61% increase of nitrite oxidoreductase respectively compared to the control. Fe(II) promotion was also observed on Nitrosomonas, Nitrospira, Azospira, and Zoogloea by 1.00-6.50 folds, which might result from higher expression of nitrogen fixation and nitrite redox genes. These findings could be explanation for increase of ammonium removal by 7.47-8.75% with Fe(II) addition, and reduction of nitrate accumulation with 30 mg/L Fe(II). Meanwhile, both Fe(II) stimulation on PAOs like Dechloromonas, Rhodococcus, Mesorhizobium, and Methylobacterium by 1.58-2.00 folds, and improvement on chemical phosphorus removal contributed to higher total phosphorus removal efficiency under high-level PFOA exposure. Moreover, Fe(II) raised chlorophyll content and reduced the oxidative damage brought by PFOA, especially at lower dosage. Nevertheless, combination of Fe(II) and high-level PFOA caused inhibition on microbial alpha diversity, which could result in decline of PFOA removal (by 4.29-12.83%). Besides, decrease of genes related to nitrate reduction demonstrated that enhancement on denitrification was due to nitrite reduction to N2 pathways rather than the first step of denitrifying process.
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Caprilatos , Desnitrificación , Fluorocarburos , Hierro , Hierro/metabolismo , Nitratos/metabolismo , Nitritos , Eliminación de Residuos Líquidos , Humedales , Fósforo , Compuestos Ferrosos , NitrógenoRESUMEN
Castration-resistant prostate cancer (CRPC) is an aggressive disease with poor prognosis, and there is an urgent need for more effective therapeutic targets to address this challenge. Here, we showed that dihydroorotate dehydrogenase (DHODH), an enzyme crucial in the pyrimidine biosynthesis pathway, is a promising therapeutic target for CRPC. The transcript levels of DHODH were significantly elevated in prostate tumors and were negatively correlated with the prognosis of patients with prostate cancer. DHODH inhibition effectively suppressed CRPC progression by blocking cell cycle progression and inducing apoptosis. Notably, treatment with DHODH inhibitor BAY2402234 activated androgen biosynthesis signaling in CRPC cells. However, the combination treatment with BAY2402234 and abiraterone decreased intratumoral testosterone levels and induced apoptosis, which inhibited the growth of CWR22Rv1 xenograft tumors and patient-derived xenograft organoids. Taken together, these results establish DHODH as a key player in CRPC and as a potential therapeutic target for advanced prostate cancer.
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Androstenos , Apoptosis , Dihidroorotato Deshidrogenasa , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH , Neoplasias de la Próstata Resistentes a la Castración , Ensayos Antitumor por Modelo de Xenoinjerto , Masculino , Humanos , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Animales , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/antagonistas & inhibidores , Ratones , Androstenos/farmacología , Androstenos/uso terapéutico , Línea Celular Tumoral , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacosRESUMEN
Emerging evidence suggests a beneficial role of rhizobacteria in ameliorating plant disease resistance in an environment-friendly way. In this study, we characterize a rhizobacterium, Bacillus cereus NJ01, that enhances bacterial pathogen resistance in rice and Arabidopsis. Transcriptome analyses show that root inoculation of NJ01 induces the expression of salicylic acid (SA)- and abscisic acid (ABA)-related genes in Arabidopsis leaves. Genetic evidence showed that EDS1, PAD4, and WRKY18 are required for B. cereus NJ01-induced bacterial resistance. An EDS1-PAD4 complex interacts with WRKY18 and enhances its DNA binding activity. WRKY18 directly binds to the W box in the promoter region of the SA biosynthesis gene ICS1 and ABA biosynthesis genes NCED3 and NCED5 and contributes to the NJ01-induced bacterial resistance. Taken together, our findings indicate a role of the EDS1/PAD4-WRKY18 complex in rhizobacteria-induced disease resistance.
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Ácido Abscísico , Proteínas de Arabidopsis , Arabidopsis , Bacillus cereus , Proteínas de Unión al ADN , Enfermedades de las Plantas , Ácido Salicílico , Bacillus cereus/genética , Ácido Abscísico/metabolismo , Arabidopsis/inmunología , Arabidopsis/microbiología , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/inmunología , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Ácido Salicílico/metabolismo , Regulación de la Expresión Génica de las Plantas , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Oryza/microbiología , Oryza/inmunología , Oryza/genética , Resistencia a la Enfermedad/genética , Resistencia a la Enfermedad/inmunología , Inmunidad de la PlantaRESUMEN
The plastic waste issue has posed a series of formidable challenges for the ecological environment and human health. While conventional recycling strategies often lead to plastic down-cycling, the electrochemical strategy of recovering valuable monomers enables an ideal, circular plastic economy. Here a corrosion synthesized single atom Pt1/Ni(OH)2 electrocatalyst with part-per-million noble Pt loading for highly efficient and selective upcycling of polyethylene terephthalate (PET) into valuable chemicals (potassium diformate and terephthalic acid) and green hydrogen is reported. Electro-oxidation of PET hydrolysate, ethylene glycol (EG), to formate is processed with high Faraday efficiency (FE) and selectivity (>90%) at the current density close to 1000 mA cm-2 (1.444 V vs RHE). The in situ spectroscopy and density functional theory calculations provide insights into the mechanism and the understanding of the high efficiency. Remarkably, the electro-oxidation of EG at the ampere-level current density is also successfully illustrated by using a membrane-electrode assembly with high FEs to formate integrated with hydrogen production for 500 h of continuous operation. This process allows valuable chemical production at high space-time yield and is highly profitable (588-700 $ ton-1 PET), showing an industrial perspective on single-atom catalysis of electrochemical plastic upcycling.
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Background: Treatment options remain rather limited for extensive disease small cell lung cancer (ED-SCLC) patients in second or further-line setting. Methods: The phase 2 investigator-initiated non-randomized study enrolled patients who had disease progression on at least one line of platinum-based chemotherapy. Participants received intravenous sintilimab 200 mg on day one and oral daily anlotinib 12 mg on days 1-14 once every three weeks per cycle. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety. This study is registered with ClinicalTrials.gov (NCT04055792). Findings: Forty-two patients were enrolled between August 29, 2019 and December 26, 2021 at Henan Cancer Hospital in China. 37 patients were evaluable for efficacy. The median follow-up was 24.8 months (IQR: 16.9-28.2). The median PFS was 6.1 months (95% CI: 5.0-7.3). The OS was 12.7 months (95% CI: 7.1-18.2). The ORR was 56.8% (21/37, 95% CI: 40.0-73.5) and the DCR was 89.2% (33/37, 95% CI: 78.7-99.7). Forty patients (40/42, 95%) had at least one treatment-related adverse event (TRAE). Immune-related adverse events (irAEs) were reported in 39 patients (39/42, 93%), while grade 3 or higher irAEs occurred in 11 patients (11/42, 26%). The most frequent irAEs were hypothyroidism (16/42, 38%), elevated gamma-glutamyl transpeptidase (15/42, 36%) and elevated creatine kinase MB (15/42, 36%). The most frequent grade 3 or higher irAEs were elevated gamma-glutamyl transpeptidase (5/42, 12%) and increased aspartate aminotransferase (3/42, 7%). Interpretation: Sintilimab plus anlotinib demonstrated promising antitumor activities as second or further-line therapy for ED-SCLC and had manageable toxicities. The findings support further randomized controlled trials of this combination regimen for ED-SCLC. Funding: Henan Province Health and Youth Subject Leader Training Project, Henan Health Science and Technology Innovation Talents, ZHONGYUAN QIANREN JIHUA, Henan International Joint Laboratory of drug resistance and reversal of targeted therapy for lung cancer, Tumor Research Fund of Anti-Angiogenesis Targeted Therapy of China Anti-Cancer Association.
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RATIONALE AND OBJECTIVES: The purpose of this study is to delineate cross-sectional associations between qualitative and quantitative measures of the infrapatellar fat pad (IPFP) and knee symptoms, structure, kinematics, and kinetics in older adults. METHODS: Ninety eligible subjects (90 knees, mean age 54.0 years, 68.9% female) were examined at our center. We used T2-weighted fat-suppressed magnetic resonance imaging (MRI) to evaluate signal intensity alteration, maximum sagittal area, and depth of the IPFP. Symptomatic osteoarthritis (SOA) was a pain subscale score greater than 0 on the Western Ontario McMaster Osteoarthritis Index. A Kellgren-Lawrence grade ≥ 2 identified incident radiographic osteoarthritis (iROA). Three-dimensional gait data were employed to analyze knee joint kinematics and kinetics. Correlation and regression analyzes assessed associations between IPFP measurements and SOA, iROA, kinematics, and kinetics. RESULTS: There were strong and positive associations between IPFP signal intensity alteration and both SOA and iROA in multivariable regression analyzes [OR (95% CI): 2.849 (1.440 to 5.636), 2.356 (1.236 to 4.492), respectively]. Conversely, a significant negative correlation was observed between IPFP maximum area and flexion angle [B (95%CI): - 1.557 (-2.549 to -0.564)]. Moreover, adjusting for covariates did not reveal any significant correlation between IPFP parameters and other indicators (P > 0.05, respectively). CONCLUSION: IPFP signal intensity alteration and area were associated with knee clinical symptoms, structural abnormalities, and flexion angle in adults over 40, respectively. These findings suggest that IPFP may be a crucial imaging biomarker in early and middle knee osteoarthritis.
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Tejido Adiposo , Articulación de la Rodilla , Imagen por Resonancia Magnética , Osteoartritis de la Rodilla , Humanos , Femenino , Masculino , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/fisiopatología , Persona de Mediana Edad , Fenómenos Biomecánicos , Tejido Adiposo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Estudios Transversales , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/fisiopatología , Anciano , Artralgia/diagnóstico por imagen , Artralgia/fisiopatología , Cinética , Rótula/diagnóstico por imagen , Rótula/fisiopatologíaRESUMEN
OBJECTIVE: To analyze the factors associated with EGFR-mutated lung cancer with leptomeningeal metastasis (LM) in the real world that affects the prognosis of patients. MATERIALS AND METHODS: The clinical data of 123 patients with advanced EGFR mutated lung cancer combined with LM treated at Henan Cancer Hospital and confirmed by histology between January 2016 and December 2020 were retrospectively collected, and all patients were followed up until September 2021. Analyze the median overall survival (mOS) time of patients with clinical characteristics and treatment factors to explore the factors influencing the prognosis of lung cancer patients with LM. RESULTS: A total of 123 patients with EGFR-mutated lung cancer and LM were included in this study. Overall, patients with exon 19 deletion (19del) in the classical mutation of the EGFR gene had a prolonged mOS compared to patients with exon 21 L858R mutation (21L858R) (30.1 months vs. 26.0 months); patients with primary LM (mOS 21.2 months) had a significantly shorter mOS than those with secondary LM (mOS 28.3 months); mOS was also significantly shorter in patients with combined brain metastases (mOS of 25.4 months) than in patients without combined brain metastases (mOS of 33.4 months); Patients treated with tyrosine kinase inhibitors (TKI) combined with antiangiogenic therapy (bevacizumab) experienced delayed onset of LM (mOS1: 19.4 months vs. 13.9 months), and prolonged survival after LM compared with those treated with EGFR-TKI alone (mOS2: 14.5 months vs. 10.0 months); There is no survival benefit to the patients treated with EGFR-TKI combined with chemotherapy compared to the patients treated with EGFR-TKI alone. CONCLUSION: Among NSCLC-LM patients with EGFR mutation, receiving EGFR-TKI combined with antiangiogenic therapy may result in a better survival benefit. The factors of primary LM, combined brain metastasis may be prognostic factors for poor OS.
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Receptores ErbB , Neoplasias Pulmonares , Mutación , Humanos , Masculino , Estudios Retrospectivos , Receptores ErbB/genética , Femenino , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Persona de Mediana Edad , Pronóstico , Mutación/genética , Anciano , Adulto , Tasa de Supervivencia , Neoplasias Meníngeas/secundario , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinomatosis Meníngea/secundario , Carcinomatosis Meníngea/genética , Carcinomatosis Meníngea/tratamiento farmacológico , Estudios de Seguimiento , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/genética , Anciano de 80 o más Años , Inhibidores de Proteínas Quinasas/uso terapéuticoRESUMEN
Two-dimensional van der Waals heterostructures (2D vdWhs) are of significant interest due to their intriguing physical properties critically defined by the constituent monolayers and their interlayer coupling. Synthetic access to 2D vdWhs based on chemically tunable monolayer organic 2D materials remains challenging. Herein, the fabrication of a novel organic-inorganic bilayer vdWh by combining π-conjugated 2D coordination polymer (2DCP, i.e., Cu3BHT, BHT = benzenehexathiol) with graphene is reported. Monolayer Cu3BHT with detectable µm2-scale uniformity and atomic flatness is synthesized using on-water surface chemistry. A combination of diffraction and imaging techniques enables the determination of the crystal structure of monolayer Cu3BHT with atomic precision. Leveraging the strong interlayer coupling, Cu3BHT-graphene vdWh exhibits highly efficient photoinduced interlayer charge separation with a net electron transfer efficiency of up to 34% from Cu3BHT to graphene, superior to those of reported bilayer 2D vdWhs and molecular-graphene vdWhs. This study unveils the potential for developing novel 2DCP-based vdWhs with intriguing physical properties.