RESUMEN
Secondary injury following spinal cord injury is primarily characterized by a complex inflammatory response, with resident microglia and infiltrating macrophages playing pivotal roles. While previous studies have grouped these two cell types together based on similarities in structure and function, an increasing number of studies have demonstrated that microglia and macrophages exhibit differences in structure and function and have different effects on disease processes. In this study, we used single-cell RNA sequencing and spatial transcriptomics to identify the distinct evolutionary paths of microglia and macrophages following spinal cord injury. Our results showed that microglia were activated to a pro-inflammatory phenotype immediately after spinal cord injury, gradually transforming to an anti-inflammatory steady state phenotype as the disease progressed. Regarding macrophages, our findings highlighted abundant communication with other cells, including fibroblasts and neurons. Both pro-inflammatory and neuroprotective effects of macrophages were also identified; the pro-inflammatory effect may be related to integrin ß2 (Itgb2) and the neuroprotective effect may be related to the oncostatin M pathway. These findings were validated by in vivo experiments. This research underscores differences in the cellular dynamics of microglia and macrophages following spinal cord injury, and may offer new perspectives on inflammatory mechanisms and potential therapeutic targets.
RESUMEN
Memristive systems have potential applications in nonvolatile memories and even unexplored functionalities in electronics. However, progress has been delayed by difficulties in the controllability of memory behaviors and the dependence on material conductivity. Considering this, a new depletion-region width modulation model is proposed to realize and explain memory characteristics. The coexistence of memristive and memcapacitive behaviors is demonstrated in p-CuAlO2/n-ZnO, p+-Si/n-ZnO and p-NiO/n-ZnO heterostructure devices. A high external electric field induces the migration of oxygen ions and electrons/holes between the p-type and n-type semiconductor layers. It can regulate the oxygen vacancy concentration of the n-type side and cation vacancy concentration of the p-type side, changing the depletion-region width and modulating device conductivity and capacitance. Several essential synaptic functions were accurately imitated, including spike-timing-dependent plasticity (STDP) and "learning-experience" behaviors. This work provides new opportunities in fabricating a memristor and memcapacitor based on a PN heterostructure for synaptic simulation.
RESUMEN
We demonstrate a lithium (Li) imbued TiOx iontronic device that exhibits synapse-like short-term plasticity behavior without requiring a forming process beforehand or a compliance current during switching. A solid-state electrolyte lithium phosphorus oxynitride (LiPON) behaves as the ion source, and the embedding and releasing of Li ions inside the cathodic like TiOx renders volatile conductance responses from the device and offers a natural platform for hardware simulating neuron functionalities. Besides, these devices possess high uniformity and great endurance as no conductive filaments are present. Different short-term pulse-based phenomena, including paired pulse facilitation, post-tetanic potentiation, and spike rate-dependent plasticity, were observed with self-relaxation characteristics. Based on the voltage excitation period, the time scale of the volatile memory can be tuned. Temperature measurement reveals the ion displacement-induced conductance channels become frozen below 220 K. In addition, the volatile analog devices can be configured into nonvolatile memory units with multibit storage capabilities after an electroforming process. Therefore, on the same platform, we can configure volatile units as nonlinear dynamic reservoirs for performing neuromorphic training and the nonvolatile units as the weight storage layer. We proceed to use voice recognition as an example with the tunable time constant relationship and obtain 94.4% accuracy with a minimal training data set. Thus, this iontronic platform can effectively process and update temporal information for reservoir and neuromorphic computing paradigms.
RESUMEN
Body weight (BW) is an important economic trait in chickens. The hypothalamus serves as a central regulator of appetite and energy balance, and extensive research has demonstrated its pivotal role in regulating BW. However, the molecular network of the hypothalamus regulating BW traits in chickens needs to be further illuminated. In the present study, 200 1-day-old male 817 broilers were reared to 50 d of age, and BW were recorded. 20 birds with the lowest BW were classified as the low body weight group (L-BWG), and 20 birds with the highest BW were classified as the high body weight group (H-BWG). 18 hypothalamic tissue samples were collected, including 5 from the L-BWG, 5 from the H-BWG, and 8 from the middle weight range, and were analyzed using RNA-seq and weighted gene co-expression network analysis (WGCNA). Among the 18 RNA-seq samples, 5 samples from the L-BWG and 5 from the H-BWG were selected for differential expression gene analysis. Compared with the L-BWG, 195 and 1,241 genes were upregulated and downregulated in the H-BWG, respectively. The WGCNA analysis classified all co-expressed genes in the hypothalamus of 817 broilers into 20 modules. Among these modules, the pink module was identified as significantly negatively (r = -0.81, P = 4×10-5) associated with BW. Furthermore, several genes, including Wnt family member 6 (WNT6), growth differentiation factor 11 (GDF11), bone morphogenetic protein 4 (BMP4), and erb-b2 receptor tyrosine kinase 4 (ERBB4), involved in "regulation of developmental process" and "response to growth factor," were identified as hub genes that contribute to the regulation of BW. These results provide valuable information for further understanding of the gene expression and regulation affecting BW traits and will contribute to the molecular breeding of chickens in the future.
RESUMEN
Trans-activating transcriptional activator (TAT), a cell-penetrating peptide, has been extensively used for facilitating cellular uptake and nuclear targeting of drug delivery systems. However, the positively charged TAT peptide usually strongly interacts with serum components and undergoes substantial phagocytosis by the reticuloendothelial system, causing a short blood circulation in vivo. In this work, an acid-active tumor targeting nanoplatform DA-TAT-PECL was developed to effectively inhibit the nonspecific interactions of TAT in the bloodstream. 2,3-dimethylmaleic anhydride (DA) was first used to convert the TAT's amines to carboxylic acid, the resulting DA-TAT was further conjugated to poly(ethylene glycol)-poly(ε-caprolactone) (PEG-PCL, PECL) to get DA-TAT-PECL. After self-assembly into polymeric micelles, they were capable of circulating in the physiological condition for a long time and promoting cell penetration upon accumulation at the tumor site and de-shielding the DA group. Moreover, camptothecin (CPT) was used as the anticancer drug and modified into a dimer (CPT)2-ss-Mal, in which two CPT molecules were connected by a reduction-labile maleimide thioether bond. The Förster resonance energy transfer (FRET) signal between CPT and maleimide thioether bond was monitored to visualize the drug release process and effective targeted delivery of antitumor drugs was demonstrated. This pH/reduction dual-responsive micelle system provides a new platform for high fidelity cancer therapy.
RESUMEN
[This corrects the article DOI: 10.1371/journal.pone.0125429.].
RESUMEN
A new phthalide derivative named paramlyktone (1) and a new arborinane-type triterpenoid named paramyrpenoid (2), together with ten previously described trichothecenes derivatives (3-12) were isolated and identified from a rhizospheric soil-derived Paramyrothecium sp. KMU22107 associated with Delphinium yunnanense. Their structural elucidation was achieved by the comprehensive analysis of spectroscopic data and comparison with literature values. Notably, paramyrpenoid (2) was the first example of an arborinane-type triterpenoid with a double bond at Δ12(13) and an additional methyl motif at C-8. This was the first report of arborinane-type triterpenoids from a fungus belonging to Paramyrothecium genus. In pharmacological studies, paramyrpenoid (2) demonstrated significant cytotoxic activity against the HL-60, SW480, A-549, MDA-MB-231 and SMMC-7721 cell lines, with IC50 values from 2.0 to 16.1 µM. Compounds 1 and 2 were also evaluated for anti-inflammatory, anti-acetylcholinesterase (AChE), and protein tyrosine phosphatase 1B (PTP1B) inhibitory activities in vitro.
RESUMEN
African swine fever (ASF) is a highly contagious and severe hemorrhagic disease caused by the African swine fever virus (ASFV). The continuous spread of ASFV affects the safety of the global meat supply; therefore, the establishment of sensitive and specific detection methods for ASFV has become an important hot spot in food safety. Herein, we developed a flexible magnetoelastic (ME) biosensor based on PDMS/FeSiB/QDs composite films for the detection of ASFV P72 protein. Based on the high luminescence performance of CsPbBr3 quantum dots and the excellent magnetoelastic effect of FeSiB, flexible ME biosensors convert stress signals generated by antibody-antigen-specific binding into optical and electromagnetic signals. The nanostructures covalently linked by quantum dots and PDMS provide biomodification sites for ASFV P72 antibodies, simplifying the functionalization modification process compared to the case of conventional biosensors. The deformation of the PDMS film is amplified, and the conversion of surface stress signals to electrical signals is enhanced by exposing the biosensor to a uniform magnetic field. The experimental results proved that the flexible ME biosensor has a wide linear range of 10 ng mL-1-100 µg mL-1, and the detection limit is as low as 0.079 ng mL-1. Moreover, the flexible ME biosensor also shows good stability, sensitivity and specificity, confirming the potential for early disease screening.
Asunto(s)
Virus de la Fiebre Porcina Africana , Técnicas Biosensibles , Dimetilpolisiloxanos , Puntos Cuánticos , Técnicas Biosensibles/métodos , Virus de la Fiebre Porcina Africana/aislamiento & purificación , Dimetilpolisiloxanos/química , Puntos Cuánticos/química , Animales , Proteínas Virales/química , Porcinos , Elasticidad , Límite de DetecciónRESUMEN
Microstructural engineering is regarded as a promising option for fabricating high-performance carbon anodes. Hence, a facile solvothermal-assisted low-temperature calcination strategy was employed to modulate the microstructure of semicoke-derived carbon anodes. Owing to the effective pseudo-graphite phase modulation, the modified carbon anode exhibited a significant increase in capacity, cycling stability and ion kinetics in both lithium-ion batteries and sodium-ion batteries. Kinetic analysis and in-situ X-ray diffraction confirmed the "adsorption and intercalation" energy storage mechanism of the obtained carbon electrodes. In addition, by investigating the energy storage mechanism, we found that increasing the pseudo-graphite phase proportion played different roles in lithium and sodium ions storage. For lithium-ion storage, the pseudo-graphitic phase preferentially promotes lithium-ion transport kinetics. Conversely, during sodium-ion storage, this particular structure markedly augments the embedding capacity of sodium. Theoretical calculations demonstrate that different patterns of variation in the activation energy with the carbon layer spacing of lithium/sodium intercalation compounds lead to differences in performance enhancement. This study not only offers a low-cost approach for preparing carbon anodes enriched with a pseudo-graphitic phase, but also provides new insight into the discrepancy between lithium ion and sodium ion storage.
RESUMEN
Photosensitizer-based phototherapies, including photodynamic therapy (PDT) and photothermal therapy (PTT), offer safe treatment modalities for tumor ablation with spatiotemporal precision. After photons are absorbed, PDT creates localized chemical damage by generating reactive oxygen species (ROS), while PTT induces localized thermal damage. However, PDT still faces hypoxic tumor challenges, while PTT encounters issues related to heat resistance and potential overheating. The combination of PDT and PTT shows great potential as an effective anticancer strategy. By targeting lysosomes with carefully designed phototherapeutic reagents for combined phototherapy, rapid dysfunction and cell death in cancer cells can be induced, showing promise for cancer treatment. Herein, two α-α-linked bisBODIPYs with tetraphenylethene (TPE) moieties are designed and synthesized. These TPE-substituted bisBODIPYs expand the absorption into NIR range (λmaxabs/λmaxem â¼ 740/810 nm) and confer aggregation-induced emission (AIE) activity (λmaxem â¼ 912 nm). Moreover, these bisBODIPYs self-assemble with surfactant F-127 into nanoparticles (NPs), which efficiently generate ROS (1O2 and â¢OH) in both solution and cellular environments and demonstrate superior photothermal conversion efficiencies (η â¼ 68.3%) along with exceptional photothermal stability. More importantly, these NPs showed lysosomal targeting and remarkable tumor ablation in cellular and murine models, indicating their potential in precision tumor therapy.
Asunto(s)
Lisosomas , Nanopartículas , Fármacos Fotosensibilizantes , Lisosomas/metabolismo , Lisosomas/efectos de los fármacos , Humanos , Animales , Ratones , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Nanopartículas/química , Rayos Infrarrojos , Fotoquimioterapia , Estilbenos/química , Estilbenos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Fototerapia , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Ratones Endogámicos BALB C , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Neoplasias/patología , Ratones DesnudosRESUMEN
Controlling the structure and chemistry of solid electrolyte interphase (SEI) underpins the stability of electrolyte-electrode interface, and is crucial for advancing rechargeable lithium metal batteries (LMBs). Here, we utilized photo-controlled copolymerization to achieve the on-demand synthesis of fluorosulfonyl fluoropolymers as unprecedented artificial SEI layers on Li metal anodes. This work not only enables instant formation of a hybrid polymer-inorganic interphase that consists of a polymer-enriched top layer and a LiF-fortified bottom layer, originating from a single polymeric component, but also imparts various desirable physical properties (e.g., good mechanical strength and flexibility, high ion conductivity, low overpotential) to SEI via a single-to-divergent strategy. Model reactions and structural characterizations supported the formation of a divergent fluorinated interphase, which furnished prolonged stabilization of Li deposition, high coulombic efficiency and improved cycling behavior in electrochemical experiments. This work highlights the great potential of exploring reactive polymers as versatile coatings to stabilize Li metal anodes, providing a promising avenue to solve electrode-electrolyte interfacial problems for LMBs.
RESUMEN
Hypoxic pulmonary hypertension (HPH) is a serious and life-threatening chronic cardiopulmonary disease characterized by progressive elevation of pulmonary artery pressure and pulmonary vascular remodeling. Mesenchymal stem cell- derived exosomes (MSC-Exos) can relieve HPH by reversing pulmonary vascular remodeling. The HPH model was established in healthy male Sprague-Dawley (SD) rats aged 6 to 8 weeks. The rats were placed in a room with oxygen concentration of (10 ± 1) % for 8 hours a day over 28 days, were then injected intravenously with MSC-Exos (100 ug protein/kg) or equal-volume phosphate buffer saline (PBS) once a day over 1 week. Right ventricular systolic pressure (RVSP), right ventricular hypertrophy index (RVHI) and pulmonary vascular remodeling were observed after anesthesia. In addition, platelet-derived growth factor BB (PDGF-BB) was used to stimulate rat pulmonary artery smooth muscle cells (PASMCs) to construct HPH pathological cell models. The results showed that MSC-Exos could not only reduce the elevation of RVSP, right ventricular hypertrophy and the degree of pulmonary vascular remodeling in HPH rats, but also reduce the proliferation, migration and apoptosis resistance of PASMCs. Finally, GSE53408 and GSE113439 datasets were analyzed and showed that the expression of Hsp90aa1 and pERK/ERK were significantly increased in HPH, also could be inhibited by MSC-Exos. Meanwhile, inhibition of Hsp90aa1 also reduced PASMCs migration and pERK/ERK protein level. In conclusion, MSC-Exos alleviated HPH by suppressing PASMCs proliferation, migration and apoptosis resistance through inhibiting the Hsp90aa1/ERK/pERK pathway.
Asunto(s)
Exosomas , Proteínas HSP90 de Choque Térmico , Hipertensión Pulmonar , Sistema de Señalización de MAP Quinasas , Células Madre Mesenquimatosas , Ratas Sprague-Dawley , Animales , Exosomas/metabolismo , Exosomas/trasplante , Masculino , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/terapia , Células Madre Mesenquimatosas/metabolismo , Ratas , Proteínas HSP90 de Choque Térmico/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , Hipoxia/metabolismo , Hipoxia/terapia , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/fisiologíaRESUMEN
Controlled radical copolymerizations present attractive avenues to obtain polymers with complicated compositions and sequences. In this work, we report the development of a visible-light-driven organocatalyzed controlled copolymerization of fluoroalkenes and acyclic N-vinylamides for the first time. The approach enables the on-demand synthesis of a broad scope of amide-functionalized main-chain fluoropolymers via novel fluorinated thiocarbamates, facilitating regulations over chemical compositions and alternating fractions by rationally selecting comonomer pairs and ratios. This method allows temporally controlled chain-growth by external light, and maintains high chain-end fidelity that promotes facile preparation of block sequences. Notably, the obtained F/N hybrid polymers, upon hydrolysis, afford free amino-substituted fluoropolymers versatile for post modifications toward various functionalities (e.g., amide, sulfonamide, carbamide, thiocarbamide). We further demonstrate the in situ formation of polymer networks with desirable properties as protective layers on lithium metal anodes, presenting a promising avenue for advancing lithium metal batteries.
RESUMEN
PURPOSE: This scoping review aimed to understand the advances in radiomics in esophagogastric junction (EGJ) cancer and assess the current status of radiomics in EGJ cancer. METHODS: We conducted systematic searches of PubMed, Embase, and Web of Science databases from January 18, 2012, to January 15, 2023, to identify radiomics articles related to EGJ cancer. Two researchers independently screened the literature, extracted data, and assessed the quality of the studies using the Radiomics Quality Score (RQS) and the METhodological RadiomICs Score (METRICS) tool, respectively. RESULTS: A total of 120 articles were retrieved from the three databases, and after screening, only six papers met the inclusion criteria. These studies investigated the role of radiomics in differentiating adenocarcinoma from squamous carcinoma, diagnosing T-stage, evaluating HER2 overexpression, predicting response to neoadjuvant therapy, and prognosis in EGJ cancer. The median score percentage of RQS was 34.7% (range from 22.2% to 38.9%). The median score percentage of METRICS was 71.2% (range from 58.2% to 84.9%). CONCLUSION: Although there is a considerable difference between the RQS and METRICS scores of the included literature, we believe that the research value of radiomics in EGJ cancer has been revealed. In the future, while actively exploring more diagnostic, prognostic, and biological correlation studies in EGJ cancer, greater emphasis should be placed on the standardization and clinical application of radiomics.
Asunto(s)
Neoplasias Esofágicas , Unión Esofagogástrica , Neoplasias Gástricas , Humanos , Unión Esofagogástrica/diagnóstico por imagen , Neoplasias Esofágicas/diagnóstico por imagen , Neoplasias Gástricas/diagnóstico por imagen , Pronóstico , RadiómicaRESUMEN
Carcass appearance is important economic trait, which affects customers in making purchase decisions. Both density and diameter of feather follicles are two important indicators of carcass appearance. However, the regulatory network and key genes be involved in feather follicle development remain poorly understood. To identify key genes and modules that involved in feather follicle development in chickens, 16 transcriptome datasets of Wannan chickens skin tissue (3 birds at the E9, E11, and E14, respectively, and 7 birds at the 12W) were used for weighted gene co-expression network analysis (WGCNA) analysis, and 12 skin tissue samples (3 birds for each stage) were selected for DEGs analysis. A total of 5,025, 2,337, and 10,623 DEGs were identified in 3 comparison groups, including the E9 vs. E11, the E11 vs. E14, and the E14 vs. 12W. Additionally, 31 co-expression gene modules were identified by WGCNA and the dark-orange, cyan, and blue module were found to be significantly associated with feather follicle development (p < 0.01). In total, 92,898 and 8,448 hub genes were obtained in the dark-orange, cyan, and blue modules, respectively. We focused on the cyan and blue modules, as 6 and 336 hub genes of these modules were identified to overlap with the DEGs of the three comparison groups, respectively. The 6 overlapped genes such as LAMC2, COL6A3, and COL6A2 etc., were over-represented in 12 categories such as focal adhesion and ECM-receptor interaction signaling pathway. Among the 336 genes that overlapped between the blue module and different DEGs comparison groups several genes including WNT7A and WNT9B were enriched in Wnt and ECM-receptor interaction signaling pathway. These results suggested that the LAMC2, COL6A3, COL6A2, WNT7A, and WNT9B genes may play a crucial role in the regulation of feather follicle development in Wannan chickens. Our results provided a reference for the molecular regulatory network and key genes in the development of feather follicles and contribute to molecular breeding for carcass appearance traits in chickens.
Asunto(s)
Pollos , Plumas , Redes Reguladoras de Genes , Animales , Pollos/genética , Pollos/fisiología , Pollos/crecimiento & desarrollo , Transcriptoma , Perfilación de la Expresión Génica/veterinaria , Proteínas Aviares/genética , Proteínas Aviares/metabolismoRESUMEN
Endogenous retroviruses (ERVs) are related to long terminal repeat (LTR) retrotransposons, comprising gene sequences of exogenous retroviruses integrated into the host genome and inherited according to Mendelian law. They are considered to have contributed greatly to the evolution of host genome structure and function. We previously characterized HERV-K HML-9 in the human genome. However, the biological function of this type of element in the genome of the chimpanzee, which is the closest living relative of humans, largely remains elusive. Therefore, the current study aims to characterize HML-9 in the chimpanzee genome and to compare the results with those in the human genome. Firstly, we report the distribution and genetic structural characterization of the 26 proviral elements and 38 solo LTR elements of HML-9 in the chimpanzee genome. The results showed that the distribution of these elements displayed a non-random integration pattern, and only six elements maintained a relatively complete structure. Then, we analyze their phylogeny and reveal that the identified elements all cluster together with HML-9 references and with those identified in the human genome. The HML-9 integration time was estimated based on the 2-LTR approach, and the results showed that HML-9 elements were integrated into the chimpanzee genome between 14 and 36 million years ago and into the human genome between 18 and 49 mya. In addition, conserved motifs, cis-regulatory regions, and enriched PBS sequence features in the chimpanzee genome were predicted based on bioinformatics. The results show that pathways significantly enriched for ERV LTR-regulated genes found in the chimpanzee genome are closely associated with disease development, including neurological and neurodevelopmental psychiatric disorders. In summary, the identification, characterization, and genomics of HML-9 presented here not only contribute to our understanding of the role of ERVs in primate evolution but also to our understanding of their biofunctional significance.
Asunto(s)
Retrovirus Endógenos , Evolución Molecular , Genoma , Pan troglodytes , Filogenia , Secuencias Repetidas Terminales , Animales , Retrovirus Endógenos/genética , Humanos , Genoma Humano , Provirus/genética , Integración Viral , RetroelementosRESUMEN
BACKGROUND: Liver cancer is typified by a complex inflammatory tumor microenvironment, where an array of cytokines and stromal cells orchestrate a milieu that significantly influences tumorigenesis. Interleukin-17A (IL-17A), a pivotal pro-inflammatory cytokine predominantly secreted by Th17 cells, is known to play a substantial role in the etiology and progression of liver cancer. However, the precise mechanism by which IL-17A engages with hepatic stellate cells (HSCs) to facilitate the development of hepatocellular carcinoma (HCC) remains to be fully elucidated. This investigation seeks to unravel the interplay between IL-17A and HSCs in the context of HCC. METHODS: An HCC model was established in male Sprague-Dawley rats using diethylnitrosamine to explore the roles of IL-17A and HSCs in HCC pathogenesis. In vivo overexpression of Il17a was achieved using adeno-associated virus. A suite of molecular techniques, including RT-qPCR, enzyme-linked immunosorbent assays, Western blotting, cell counting kit-8 assays and colony formation assays, was employed for in vitro analyses. RESULTS: The study findings indicate that IL-17A is a key mediator in HCC promotion, primarily through the activation of hepatic progenitor cells (HPCs). This pro-tumorigenic influence appears to be mediated by HSCs, rather than through a direct effect on HPCs. Notably, IL-17A-induced expression of fibroblast activation protein (FAP) in HSCs emerged as a critical factor in HCC progression. Silencing Fap in IL-17A-stimulated HSCs was observed to reverse the HCC-promoting effects of HSCs. CONCLUSIONS: The collective evidence from this study implicates the IL-17A/FAP signaling axis within HSCs as a contributor to HCC development by enhancing HPC activation. These findings bolster the potential of IL-17A as a diagnostic and preventative target for HCC, offering new avenues for therapeutic intervention.
Asunto(s)
Carcinoma Hepatocelular , Células Estrelladas Hepáticas , Interleucina-17 , Neoplasias Hepáticas , Animales , Humanos , Masculino , Ratas , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Modelos Animales de Enfermedad , Endopeptidasas/metabolismo , Endopeptidasas/genética , Regulación Neoplásica de la Expresión Génica , Células Estrelladas Hepáticas/metabolismo , Interleucina-17/metabolismo , Interleucina-17/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Ratas Sprague-Dawley , Microambiente TumoralRESUMEN
Spurs, which mainly appear in roosters, are protrusions near the tarsometatarsus on both sides of the calves of chickens, and are connected to the tarsometatarsus by a bony core. As a male-biased morphological characteristic, the diameter and length of spurs vary significantly between different individuals, mainly related to genetics and age. As a specific behavior of hens, egg-laying also varies greatly between individuals in terms of traits such as age at first egg (AFE), egg weight (EW), and so on. At present, there are few studies on chicken spurs. In this study, we investigated the inheritance pattern of the spur trait in roosters with different phenotypes and the correlations between spur length, body weight at 18 weeks of age (BW18), shank length at 18 weeks of age (SL18), and the egg-laying trait in hens (both hens and roosters were from the same population and were grouped according to their family). These traits related to egg production included AFE, body weight at first egg (BWA), and first egg weight (FEW). We estimated genetic parameters based on pedigree and phenotype data, and used variance analysis to calculate broad-sense heritability for correcting the parameter estimation results. The results showed that the heritability of male left and right spurs ranged from 0.6 to 0.7. There were significant positive correlations between left and right spur length, BW18, SL18, and BWA, as well as between left and right spur length and AFE. We selected 35 males with the longest spurs and 35 males with the shortest spurs in the population, and pooled them into two sets to obtain the pooled genome sequencing data. After genome-wide association and genome divergency analysis by FST, allele frequency differences (AFDs), and XPEHH methods, we identified 7 overlapping genes (CENPE, FAT1, FAM149A, MANBA, NFKB1, SORBS2, UBE2D3) and 14 peak genes (SAMD12, TSPAN5, ENSGALG00000050071, ENSGALG00000053133, ENSGALG00000050348, CNTN5, TRPC6, ENSGALG00000047655,TMSB4X, LIX1, CKB, NEBL, PRTFDC1, MLLT10) related to left and right spur length through genome-wide selection signature analysis and a genome-wide association approach. Our results identified candidate genes associated with chicken spurs, which helps to understand the genetic mechanism of this trait and carry out subsequent research around it.
RESUMEN
The degradation of cyanobacterial blooms releases hazardous contaminants such as microcystin-LR (MC-LR) and nitrite, which may collectively exert toxicity on various bodily systems. To evaluate their individual and combined toxicity in the kidney, mice were subjected to different concentrations of MC-LR and/or nitrite over a 6-month period in this study. The results revealed that combined exposure to MC-LR and nitrite exacerbated renal pathological alterations and dysfunction compared to exposure to either compound alone. Specifically, the protein and mRNA expression of kidney injury biomarkers, such as kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL), were notably increased in combined exposure group. Concurrently, co-exposure to MC-LR and nitrite remarkedly upregulated levels of proinflammatory cytokines TNF-α, IL-6 and IL-1ß, while decreasing the anti-inflammatory cytokine IL-10. Notably, MC-LR and nitrite exhibited synergistic effects on the upregulation of renal IL-1ß levels. Moreover, MC-LR combined with nitrite not only elevated mRNA levels of proinflammatory cytokines but also increased protein levels of pyroptosis biomarkers such as IL-1ß, Gasdermin D (GSDMD), and Cleaved-GSDMD. Mechanistic investigations revealed that co-exposure to MC-LR and nitrite promoted pyroptosis both in vivo and in vitro, possibly through the activation of the TLR4/NLRP3/GSDMD pathway. Pretreatment with TLR4 inhibitor and NLRP3 inhibitor effectively suppressed pyroptosis induced by the co-exposure of these two toxins in HEK293T cells. These findings provide compelling evidence that MC-LR combined with nitrite synergistically induces pyroptosis in the kidney by activating the TLR4/NLRP3/GSDMD pathway. Overall, this study significantly enhances our comprehension of how environmental toxins interact and induce harm to the kidneys, offering promising avenues for identifying therapeutic targets to alleviate their toxic effects on renal health.