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BACKGROUND & AIMS: The mechanisms underlying the regulation of hepatocyte non-receptor tyrosine kinases in metabolic dysfunction-associated steatohepatitis (MASH) remain largely unclear. METHODS: Hepatocyte-specific overexpression or deletion and anti-protein tyrosine kinase 2 beta (PYK2) or anti-TRAF6-binding protein (T6BP) crosslinking were utilised to study fatty liver protection by T6BP. P-PTC, a peptide-proteolysis targeting chimaera, degrades PYK2 to block MASH progression. RESULTS: Since PYK2 activation is promoter signalling in steatohepatitis development, we find that T6BP is a novel and critical suppressor of PYK2 that reduces hepatic lipid accumulation, pro-inflammatory factor release, and pro-fibrosis production by ubiquitin ligase CBL to degrade PYK2. Mechanistic evidence suggests that T6BP directly targets PYK2 and prevents its N-terminal FERM domain-triggered dimerization, disrupting downstream PYK2-JNK signalling hyperactivation. Additionally, T6BP favourably recruits CBL, a particular E3 ubiquitin ligase targeting PYK2, to form a complex and degrade PYK2. T6BP (F1), a core fragment of T6BP, directly blocks N-terminal FERM domain-associated dimerization of PYK2, followed by T6BP-recruiting CBL-mediated PYK2 degradation in a typical T6BP-dependent manner when the tiny fragment is specifically expressed using thyroxine binding globulin (TBG)-ground vectors. This inhibits the progression of MASH, metabolic dysfunction-associated steatotic liver disease (MASLD)-related HCC (MASH-HCC), and metabolic syndrome in dietary rodent models. First-ever peptide-proteolysis targeting chimaera (P-PTC) based on the core segment of T6BP as a ligand for targeted recruitment of CBL targeting metabolic disorders like MASH has been devised and validated in animal models. CONCLUSIONS: Our study revealed a previously unknown mechanism: identification of T6BP as a key eliminator of fatty liver strongly contributes to the development of promising therapeutic targets, and the discovery of crucial fragments of T6BP-based pharmacon that interrupt PYK2 dimerization are novel and viable treatments for fatty liver and its advanced symptoms and complications. IMPACT AND IMPLICATIONS: Excessive high-energy diet ingestion is critical in driving steatohepatitis via regulation of hepatocyte non-receptor tyrosine kinases. The mechanisms under lying the regulation of hepatocyte PYK2 in metabolic dysfunction-associated steatohepatitis (MASH) remain largely unclear. Here, we found that T6BP as a critical fatty liver eliminator has a significant impact on the development of promising therapeutic targets. Additionally, vital T6BP-based pharmacon fragments that impede PYK2 dimerization have been found, offering new and effective treatments for advanced fatty liver symptoms and complications.

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African swine fever virus (ASFV), a highly contagious pathogen characterized by a complex structure and a variety of immunosuppression proteins, causes hemorrhagic, acute, and aggressive infectious disease that severely injures the pork products and industry. However, there is no effective vaccine or treatment. The main reasons are not only the complex mechanisms that lead to immunosuppression but also the unknown functions of various proteins. This review summarizes the interaction between ASFV and the host immune system, along with the involvement of virulence-related genes and proteins, as well as the corresponding molecular mechanism of immunosuppression of ASFV, encompassing pathways such as cGAS-STING, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), Janus Kinase (JAK) and JAK Signal Transducers and Activators of Transcription (STAT), apoptosis, and other modulation. The aim is to summarize the dynamic process during ASFV infection and entry into the host cell, provide a rational insight into development of a vaccine, and provide a better clear knowledge of how ASFV impacts the host.

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White matter injury (WMI) subsequent to subarachnoid hemorrhage (SAH) frequently leads to an unfavorable patient prognosis. Previous studies have indicated that microglial M1 polarization following SAH results in the accumulation of amyloid precursor protein (APP) and degradation of myelin basic protein (MBP), thereby catalyzing the exacerbation of WMI. Consequently, transitioning microglial polarization towards the M2 phenotype (neuroprotective state) represents a potential therapeutic approach for reversing WMI. The SIRT2 gene is pivotal in neurological disorders such as neurodegeneration and ischemic stroke. However, its function and underlying mechanisms in SAH, particularly how it influences microglial function to ameliorate WMI, remain unclear. Our investigations revealed that in post-SAH, there was a temporal increase in SIRT2 expression, predominantly in the cerebral corpus callosum area, with notable colocalization with microglia. However, following the administration of the SIRT2 inhibitor AK-7, a shift in microglial polarization towards the M2 phenotype and an improvement in both short-term and long-term neuronal functions in rats were observed. Mechanistically, CO-IP experiments confirmed that SIRT2 can interact with the receptor tyrosine kinase Axl within the TAM receptor family and act as a deacetylase to regulate the deacetylation of Axl. Concurrently, the inhibition of SIRT2 by AK-7 can lead to increased expression of Axl and activation of the anti-inflammatory pathway PI3K/Akt signaling pathway, which regulates microglial M2 polarization and consequently reduces WMI. However, when Axl expression was inhibited by the injection of the shAxl virus into the lateral ventricles, the downstream signaling pathways were significantly suppressed. Rescue experiments also confirmed that the neuroprotective effects of AK-7 can be reversed by PI3K inhibitors. These data suggest that SIRT2 influences WMI by affecting microglial polarization through the Axl/PI3K/AKT pathway, and that AK-7 could serve as an effective therapeutic drug for improving neurological functions in SAH patients.

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Flexible integration spurs diverse applications in metal-organic frameworks (MOFs). However, current configurations suffer from the trade-off between MOF loadings and mechanical compliance. We report a wrinkled configuration of MOF thin films. We established an interfacial synthesis confined and controlled by a polymer topcoat and achieved multiple Turing motifs in the wrinkled thin films. These films have complete MOF surface coverage and exhibit strain tolerance up to 53.2%. The enhanced mechanical properties allow film transfer onto various substrates. We obtained membranes with large H2/CO2 selectivity (41.2) and high H2 permeance (8.46 × 103 gas permeation units), showcasing negligible defects after transfer. We also achieved soft humidity sensors on delicate electrodes by avoiding exposure to harsh MOF synthesis conditions. These results highlight the potential of wrinkled MOF thin films for plug-and-play integration.

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In the field of robot grasping detection, due to uncertain factors such as different shapes, distinct colors, diverse materials, and various poses, robot grasping has become very challenging. This article introduces a integrated robotic system designed to address the challenge of grasping numerous unknown objects within a scene from a set of α -channel images. We propose a lightweight and object-independent pixel-level generative adaptive residual depthwise separable convolutional neural network (GARDSCN) with an inference speed of around 28 ms, which can be applied to real-time grasping detection. It can effectively deal with the grasping detection of unknown objects with different shapes and poses in various scenes and overcome the limitations of current robot grasping technology. The proposed network achieves 98.88 % grasp detection accuracy on the Cornell dataset and 95.23 % on the Jacquard dataset. To further verify the validity, the grasping experiment is conducted on a physical robot Kinova Gen2, and the grasp success rate is 96.67 % in the single-object scene and 94.10 % in the multiobject cluttered scene.

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AIM: To identify an optimized strategy for the large-scale production of nanovesicles (NVs) that preserve the biological properties of exosomes (EXOs) for use in periodontal regeneration. MATERIALS AND METHODS: NVs from dental follicle stem cells (DFSCs) were prepared through extrusion, and EXOs from DFSCs were isolated. The yield of both extruded NVs (eNVs) and EXOs were quantified through protein concentration and particle number analyses. Their pro-migration, pro-proliferation and pro-osteogenesis capacities were compared subsequently in vitro. Additionally, proteomics analysis was conducted. To further evaluate the periodontal regeneration potential of eNVs and EXOs, they were incorporated into collagen sponges and transplanted into periodontal defects in rats. In vivo imaging and H&E staining were utilized to verify their biodistribution and safety. Micro-Computed Tomography analysis and histological staining were performed to examine the regeneration of periodontal tissues. RESULTS: The yield of eNVs was nearly 40 times higher than that of EXOs. Interestingly, in vitro experiments indicated that the pro-migration and pro-proliferation abilities of eNVs were superior, and the pro-osteogenesis potential was comparable to EXOs. More importantly, eNVs exhibited periodontal regenerative potential similar to that of EXOs. CONCLUSIONS: Extrusion has proven to be an efficient method for generating numerous eNVs with the potential to replace EXOs in periodontal regeneration.

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The process of grain refinement during welding significantly influences both the final microstructure and performance of the weld joint. In the present work, merits of acoustic addition in the conventional Frictions Stir Welding (FSW) process were evaluated for joining dissimilar Al/Mg alloys. To capture the near "in situ" structure around the exit hole, an "emergency stop" followed by rapid cooling using liquid nitrogen was employed. Electron Backscatter Diffraction analysis was utilized to characterize and examine the evolution of grain microstructure within the aluminum matrix as the material flowed around the exit hole. The findings reveal that two mechanisms, continuous dynamic recrystallization (CDRX) and geometric dynamic recrystallization (GDRX), jointly or alternatively influence the grain evolution process. In conventional FSW, CDRX initially governs grain evolution, transitioning to GDRX as material deformation strain and temperature increase. Subsequently, as material deposition commences, CDRX reasserts dominance. Conversely, in acoustic addition, ultrasonic vibration accelerates GDRX, promoting its predominance by enhancing material flow and dislocation movements. Even during the material deposition, GDRX remains the dominant mechanism.

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BACKGROUND: A substantial proportion of patients with metastatic clear cell renal cell carcinoma (ccRCC) cannot derive benefit from immune checkpoint inhibitor (ICI) plus anti-angiogenic agent combination therapy, making identification of predictive biomarkers an urgent need. The members of pleckstrin homology-like domain family A (PHLDA) play critical roles in multiple cancers, whereas their roles in ccRCC remain unknown. METHODS: Transcriptomic, clinical, genetic alteration and DNA methylation data were obtained for integrated analyses from TCGA database. RNA sequencing was performed on 117 primary tumors and 79 normal kidney tissues from our center. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis, gene set enrichment analysis were performed to explore transcriptomic features. Data from three randomized controlled trials (RCT), including CheckMate025, IMmotion151, JAVELIN101, were obtained for validation. RESULTS: Members of PHLDA family were dysregulated in pan-cancer. Elevated PHLDA2 expression was associated with adverse clinicopathologic parameters and worse prognosis in ccRCC. Aberrant DNA hypomethylation contributed to up-regulation of PHLDA2. An immunosuppressive microenvironment featured by high infiltrates of Tregs and cancer-associated fibroblasts, was observed in ccRCC with higher PHLDA2 expression. Utilizing data from three RCTs, the association of elevated PHLDA2 expression with poor therapeutic efficacy of ICI plus anti-angiogenic combination therapy was confirmed. CONCLUSIONS: Our study revealed that elevated PHLDA2 expression regulated by DNA hypomethylation was correlated with poor prognosis and immunosuppressive microenvironment, and highlighted the role of PHLDA2 as a robust biomarker for predicting therapeutic efficacy of ICI plus anti-angiogenic agent combination therapy in ccRCC, which expand the dimension of precision medicine.

Asunto(s)

Carcinoma de Células Renales , Epigénesis Genética , Inhibidores de Puntos de Control Inmunológico , Neoplasias Renales , Proteínas Nucleares , Microambiente Tumoral , Femenino , Humanos , Masculino , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/patología , Metilación de ADN , Regulación Neoplásica de la Expresión Génica , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Renales/genética , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Pronóstico , Microambiente Tumoral/genética

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Background: The incidence of cardiac arrest (CA) during percutaneous coronary intervention (PCI) is relatively rare. However, when it does occur, the mortality rate is extremely high. Extracorporeal cardiopulmonary resuscitation (ECPR) has shown promising survival rates for in-hospital cardiac arrests (IHCA), with low-flow time being an independent prognostic factor for CA. However, there is no definitive answer on how to reduce low-flow time. Methods: This retrospective study, conducted at a single center, included 39 patients who underwent ECPR during PCI between January 2016 and December 2022. The patients were divided into two cohorts based on whether standby extracorporeal membrane oxygenation (ECMO) was utilized during PCI: standby ECPR (SBE) (n = 13) and extemporaneous ECPR (EE) (n = 26). We compared the 30-day mortality rates between these two cohorts and investigated factors associated with survival. Results: Compared to the EE cohort, the SBE cohort showed significantly lower low-flow time (P < 0.01), ECMO operation time (P < 0.01), and a lower incidence of acute kidney injury (AKI) (P = 0.017), as well as peak lactate (P < 0.01). Stand-by ECMO was associated with improved 30-day survival (p = 0.036), while prolonged low-flow time (p = 0.004) and a higher SYNTAX II score (p = 0.062) predicted death at 30 days. Conclusions: Standby ECMO can provide significant benefits for patients who undergo ECPR for CA during PCI. It is a viable option for high-risk PCI cases and may enhance the overall prognosis. The low-flow time remains a critical determinant of survival.

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The Cajal body, a nuclear condensate, is crucial for ribonucleoprotein assembly, including small nuclear RNPs (snRNPs). While Coilin has been identified as an integral component of Cajal bodies, its exact function remains unclear. Moreover, no Coilin ortholog has been found in unicellular organisms to date. This study unveils Mug174 (Meiosis-upregulated gene 174) as the Coilin ortholog in the fission yeast Schizosaccharomyces pombe. Mug174 forms phase-separated condensates in vitro and is often associated with the nucleolus and the cleavage body in vivo. The generation of Mug174 foci relies on the trimethylguanosine (TMG) synthase Tgs1. Moreover, Mug174 interacts with Tgs1 and U snRNAs. Deletion of the mug174+ gene in S. pombe causes diverse pleiotropic phenotypes, encompassing defects in vegetative growth, meiosis, pre-mRNA splicing, TMG capping of U snRNAs, and chromosome segregation. In addition, we identified weak homology between Mug174 and human Coilin. Notably, human Coilin expressed in fission yeast colocalizes with Mug174. Critically, Mug174 is indispensable for the maintenance of and transition from cellular quiescence. These findings highlight the Coilin ortholog in fission yeast and suggest that the Cajal body is implicated in cellular quiescence, thereby preventing human diseases.

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Cuerpos Enrollados , Proteínas Nucleares , Proteínas de Schizosaccharomyces pombe , Schizosaccharomyces , Schizosaccharomyces/genética , Schizosaccharomyces/metabolismo , Cuerpos Enrollados/metabolismo , Proteínas de Schizosaccharomyces pombe/metabolismo , Proteínas de Schizosaccharomyces pombe/genética , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Humanos , Nucléolo Celular/metabolismo , Nucléolo Celular/genética , Meiosis/genética , Empalme del ARN , ARN Nuclear Pequeño/metabolismo , ARN Nuclear Pequeño/genética , Hidroliasas/metabolismo , Hidroliasas/genética , Núcleo Celular/metabolismo , Metiltransferasas

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OBJECTIVE: This study aims to elucidate the significance of VNN2 expression in peripheral blood monocytes and its clinical relevance in primary Sjögren's syndrome (pSS). METHODS: We investigated VNN2 expression by analyzing single-cell RNA sequencing (scRNA-seq) data from peripheral blood mononuclear cells. Flow cytometry was used to detect and compare VNN2 expression in total monocytes, classical monocytes (cMo), intermediate monocytes (iMo) and non-classical monocytes (ncMo). Additionally, we examined the expression of HLA, ICAM1, CD62L, ITGAM, S100A8, S100A9, CCR2, CCR6, CX3CR1 and CXCR3 in VNN2+ and VNN2- cells. We analyzed the correlation between VNN2 expression and clinical indicators and assessed the clinical utility of VNN2+ monocytes in pSS diagnosis using receiver operating characteristic curves. RESULTS: We observed high VNN2 expression in monocytes, with significantly higher levels in CD14++ monocytes compared to ncMo. VNN2+ monocytes exhibited decreased expression of HLA and CD62L and increased expression of ICAM1, ITGAM, S100A8, S100A9, CCR2, CCR6, CX3CR1 and CXCR3 compared to VNN2- monocytes. Although scRNA-seq data showed that VNN2 mRNA was upregulated, cell surface expression of VNN2 was decreased in monocytes from pSS patients compared to healthy controls. The reduced levels of VNN2+ monocyte subpopulations in pSS patients were negatively correlated with anti-ribosome antibody levels and positively correlated with complement 4 levels. Detection of VNN2 expression in monocytes can aid in the auxiliary diagnosis of pSS. CONCLUSION: Monocytes expressing cell surface VNN2 are significantly reduced in pSS patients. This suggests a potential role for VNN2 in pSS development and its potential use as a diagnostic marker for pSS.

Asunto(s)

Monocitos , Síndrome de Sjögren , Humanos , Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/inmunología , Síndrome de Sjögren/sangre , Síndrome de Sjögren/metabolismo , Monocitos/metabolismo , Monocitos/inmunología , Femenino , Masculino , Persona de Mediana Edad , Biomarcadores , Adulto , Anciano

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BACKGROUND: This study aimed to summarize the occurrence of immune-related adverse events (irAEs) and further evaluate their association with clinical outcomes in patients with advanced renal cell carcinoma (RCC) and urothelial carcinoma (UC) treated with immune checkpoint inhibitors (ICIs). METHODS: A comprehensive search of PubMed, Embase, and the Cochrane Library up to December 2023 was conducted to identify eligible studies. The details of irAEs and data regarding their correlation with clinical outcomes were extracted. R software was used for meta-analysis. RESULTS: A total of 27 studies involving 6148 patients with RCC or UC were included. The pooled overall incidence for any-grade and grade ≥ 3 irAEs was 44.2 % (95 % CI: 38.1 %-50.5 %) and 15.7 % (95 % CI: 11.4 %-21.1 %), respectively. Compared to those without any irAEs, patients with irAEs showed improved PFS (HR = 0.44, 95 % CI: 0.35-0.56, p < 0.01) and OS (HR = 0.47, 95 % CI: 0.42-0.51, p < 0.01), as well as higher ORR (OR = 3.59, 95 % CI: 3.01-4.29, p < 0.01) and DCR (OR = 4.23, 95 % CI: 3.06-5.84, p < 0.01). Subgroup analysis indicated that clinical outcome improvements were associated with the occurrence of irAEs, regardless of tumor type or ICI agent. Notably, patients with cutaneous irAEs, thyroid dysfunction, and grade ≤ 2 irAEs had a higher probability to achieve better survival benefits from ICI-based therapy, while pulmonary irAEs and grade ≥ 3 irAEs seemed to have a negative impact on OS. Additionally, systemic glucocorticoids administration did not affect survival outcomes. CONCLUSION: Our findings suggest that the occurrence of irAEs could be considered as a potential prognostic factor for predicting the efficacy of ICIs in patients with advanced RCC and UC.

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Carcinoma de Células Renales , Inhibidores de Puntos de Control Inmunológico , Neoplasias Renales , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/inmunología , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Neoplasias Renales/inmunología , Incidencia , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/inmunología , Neoplasias Urológicas/tratamiento farmacológico , Neoplasias Urológicas/inmunología , Neoplasias Urológicas/patología

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Herein, Nitrogen-doped graphyne/porous g-C3N4 composites are firstly in-situ synthesized via the ultrasound vibration of CaC2, triazine, and porous g-C3N4 in absolute ethanol. A variety of characterizations are performed to investigate the morphology, microstructure, composition, and electrical/optical features of the obtained composites, such as transmission electron microscopy, scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectra, X-ray photoelectron spectroscopy, and so forth. It is found that N-doped graphyne with flexible folds lamellar structure is intimately attached to flake g-C3N4 in the as-prepared composites. An enlargement of 1.68 and 1.44 folds for the photocatalytic degradation of levofloxacin, rhodamine B, Methylene blue, and Tetracycline is realized by N-doped graphyne/g-C3N4 in comparison with that of pristine g-C3N4, respectively. In addition, the highest NH3 production rate attains 1.71 mmol⋅gcat-1⋅h-1 for N-doped graphyne/g-C3N4, which is 5.89 times larger than that of g-C3N4 (0.29 mmol⋅gcat-1⋅h-1). The improved mechanism of photocatalysis including higher photo-response and carrier separation rate is verified by transient photo-current, transient photo-potential, Mott-Schottky plots, Tafel plots, electrochemical impedance spectroscopy, turn-over frequency, photoluminescence spectra, and UV-vis diffuse absorption spectra, etc. Overall, the current study shows that N-doped graphyne synthesized from CaC2 and triazine is a useful decoration to modulate the photocatalytic features of g-C3N4, which can also be widely extended for in-situ modification of other photocatalysts.

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The III-V nanowire (NW) structure is a good candidate for developing photodetectors. However, high-density surface states caused by the large surface-to-volume ratio severely limit their performance, which is difficult to solve in conventional ways. Here, a robust surface passivation method, using a thin layer of ZnO capping, is developed for promoting NW photodetector performance. 11 cycles of ZnO, grown on pure zinc blende high-quality GaAs NWs by atomic layer deposition, significantly alleviates the undesirable effect of the surface states, without noticeable degradation in NW morphology. An average 20-fold increase in micro-photoluminescence intensity is observed for passivated NWs, which leads to the development of detectors with high responsivity, specific detectivity, and optical gain of 9.46 × 105 A W-1, 3.93 × 1014 Jones, and 2.2 × 108 %, respectively, under low-intensity 532 nm illumination. Passivated NW detectors outperform their counterparts treated by conventional methods, so far as we know, which shows the potential and effectiveness of thin ZnO surface passivation on NW devices.

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BACKGROUND: TFE3-rearranged renal cell carcinoma (TFE3-rRCC) is a rare but highly heterogeneous renal cell carcinoma (RCC) entity, of which the clinical treatment landscape is largely undefined. This study aims to evaluate and compare the efficacy of different systemic treatments and further explore the molecular correlates. METHODS: Thirty-eight patients with metastatic TFE3-rRCC were enrolled. Main outcomes included progression-free survival (PFS), overall survival, objective response rate (ORR) and disease control rate. RNA sequencing was performed on 32 tumors. RESULTS: Patients receiving first-line immune checkpoint inhibitor (ICI) based combination therapy achieved longer PFS than those treated without ICI (median PFS: 11.5 vs. 5.1 months, P = 0.098). After stratification of fusion partners, the superior efficacy of first-line ICI based combination therapy was predominantly observed in ASPSCR1-TFE3 rRCC (median PFS: not reached vs. 6.5 months, P = 0.01; ORR: 67.5% vs. 10.0%, P = 0.019), but almost not in non-ASPSCR1-TFE3 rRCC. Transcriptomic data revealed enrichment of ECM and collagen-related signaling in ASPSCR1-TFE3 rRCC, which might interfere with the potential efficacy of anti-angiogenic monotherapy. Whereas angiogenesis and immune activities were exclusively enriched in ASPSCR1-TFE3 rRCC and promised the better clinical outcomes with ICI plus tyrosine kinase inhibitor combination therapy. CONCLUSIONS: The current study represents the largest cohort comparing treatment outcomes and investigating molecular correlates of metastatic TFE3-rRCC based on fusion partner stratification. ICI based combination therapy could serve as an effective first-line treatment option for metastatic ASPSCR1-TFE3 rRCC patients. Regarding with other fusion subtypes, further investigations should be performed to explore the molecular mechanisms to propose pointed therapeutic strategy accordingly.

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Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Carcinoma de Células Renales , Inhibidores de Puntos de Control Inmunológico , Neoplasias Renales , Proteínas de Fusión Oncogénica , Humanos , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/mortalidad , Femenino , Masculino , Persona de Mediana Edad , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Neoplasias Renales/patología , Neoplasias Renales/mortalidad , Anciano , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Proteínas de Fusión Oncogénica/genética , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Reordenamiento Génico , Biomarcadores de Tumor/genética , Resultado del Tratamiento , Pronóstico , Péptidos y Proteínas de Señalización Intracelular/genética

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Agricultural socialized service is gradually emerging as a new stimulus for enhancing the agricultural production environment. However, their precise impact on improving the agricultural ecological environment and promoting the green development of agriculture remains incompletely understood. Therefore, leveraging panel data spanning from 2003 to 2020 across 31 provinces in China, this study utilizes the bidirectional fixed effect model, moderating effect model, and spatial Durbin model to systematically assess the influence of agricultural socialized services on agricultural green development and its spatial ramifications. The findings show that (I) agricultural socialized services significantly contribute to promoting agricultural green development, particularly in regions with lower aging demographics. (II) The application of the spatial Durbin model reveals that this promotional effect does not exhibit significant spatial spillover effect. (III) The role of agricultural socialized services in fostering agricultural green development can be significantly enhanced by advancements in land transfer, agricultural technological innovations, and the improvement of rural human capital. In conclusion, the study provides a set of policy recommendations that include government financial support, facilitating land transfer, improving rural education and technical training, and promoting green production technologies to effectively promote agricultural green development.

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Agricultura , Agricultura/métodos , Humanos , China , Población Rural , Conservación de los Recursos Naturales

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Members of the vanin gene family include VNN1, VNN2 and VNN3 in humans. Although the functions of vanins have been widely examined in myeloid cells, their expression and functions have not been clarified in T lymphocytes. This study aimed to elucidate the significance of Vanin-2 (VNN2) on human peripheral blood T lymphocytes and study its expression in systemic lupus erythematosus (SLE). The differential expression of Vanins was analysed by bioinformatics. VNN2 expressions in peripheral blood T cell subsets were analysed by single-cell RNA sequencing data and flow cytometry. Changes of VNN2 expression before and after T cell activation were further clarified by western blot. The function of VNN2+ cells was studied by granzyme B and perforin detection. Changes in VNN2+ proportions in T cell subsets of SLE patients were further analysed. In the present study, only VNN2 among vanins showed distinguishable expression in T cells. VNN2+ percentages were higher in CD8+ T cells than in CD4+ T cells. VNN2+ T cells were with a higher memory T cell composition. VNN2 expression was significantly increased after T cell stimulation. VNN2+ T cells had higher levels of granzyme B and perforin secretion than VNN2- T cells. Clinically, VNN2+ percentages in T cells of SLE patients were upregulated. Together, these data suggested that VNN2 is expressed in peripheral blood T cells characterized more granzyme B and perforin secretion, and increased VNN2+ T cells in SLE patients could reflect altered T cell functions in vivo.

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Natural deep eutectic solvents (NADESs), as emerging green solvents, can efficiently extract natural products from natural resources. However, studies on the extraction of phenolic compounds from celtuce (Lactuca sativa var. augustana) leaves (CLs) by NADESs are still lacking. This study screened the NADES L-proline-lactic acid (Pr-LA), combined it with ultrasound-assisted extraction (UAE) to extract phenolic compounds from CLs, and conducted a comparative study on the extraction effect with traditional extraction solvents. Both SEM and FT-IR confirmed that Pr-LA can enhance the degree of fragmentation of cell structures and improve the extraction rate of phenolic compounds. Molecular dynamics simulation results show that Pr-LA can improve the solubility of phenolic compounds and has stronger hydrogen bonds and van der Waals interactions with phenolic compounds. Single-factor and Box-Behnken experiments optimized the process parameters for the extraction of phenolic compounds from CLs. The second-order kinetic model describes the extraction process of phenolic compounds from CLs under optimal process parameters and provides theoretical guidance for actual industrial production. This study not only provides an efficient and green method for extracting phenolic compounds from CLs but also clarifies the mechanism of improved extraction efficiency, which provides a basis for research on the NADES extraction mechanism.

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Disolventes Eutécticos Profundos , Lactuca , Fenoles , Hojas de la Planta , Fenoles/química , Fenoles/aislamiento & purificación , Hojas de la Planta/química , Lactuca/química , Disolventes Eutécticos Profundos/química , Extractos Vegetales/química , Ondas Ultrasónicas , Espectroscopía Infrarroja por Transformada de Fourier , Simulación de Dinámica Molecular , Solventes/química

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The whole-genome sequence of an African swine fever virus (ASFV) strain (HuB/HH/2019) isolated from Hubei, China, was highly similar to that of the Georgia 2007/1 strain ASFV. After infection with strong strains, domestic pigs show typical symptoms of infection, including fever, depression, reddening of the skin, hemorrhagic swelling of various tissues, and dysfunction. The earliest detoxification occurred in pharyngeal swabs at 4 days post-infection. The viral load in the blood was extremely high, and ASFV was detected in multiple tissues, with the highest viral loads in the spleen and lungs. An imbalance between pro- and anti-inflammatory factors in the serum leads to an excessive inflammatory response in the body. Immune factor expression is suppressed without effectively eliciting an immune defense. Antibodies against p30 were not detected in acutely dead domestic pigs. Sequencing of the peripheral blood mononuclear cell transcriptome revealed elevated transcription of genes associated with immunity, defense, and stress. The massive reduction in lymphocyte counts in the blood collapses the body's immune system. An excessive inflammatory response with a massive reduction in the lymphocyte count may be an important cause of mortality in domestic pigs. These two reasons have inspired researchers to reduce excessive inflammatory responses and stimulate effective immune responses for future vaccine development.

Asunto(s)

Virus de la Fiebre Porcina Africana , Fiebre Porcina Africana , Animales , Porcinos , Fiebre Porcina Africana/virología , Fiebre Porcina Africana/inmunología , Virus de la Fiebre Porcina Africana/inmunología , Virus de la Fiebre Porcina Africana/genética , Citocinas , Linfocitos/inmunología , Linfocitos/metabolismo , Genotipo , Carga Viral , Sus scrofa , Recuento de Linfocitos