RESUMEN

Graphene aerogels hold huge promise for the development of high-performance pressure sensors for future human-machine interfaces due to their ordered microstructure and conductive network. However, their application is hindered by the limited strain sensing range caused by the intrinsic stiffness of the porous microstructure. Herein, an anisotropic cross-linked chitosan and reduced graphene oxide (CCS-rGO) aerogel metamaterial is realized by reconfiguring the microstructure from a honeycomb to a buckling structure at the dedicated cross-section plane. The reconfigured CCS-rGO aerogel shows directional hyperelasticity with extraordinary durability (no obvious structural damage after 20 000 cycles at a directional compressive strain of ≤0.7). The CCS-rGO aerogel pressure sensor exhibits an ultrahigh sensitivity of 121.45 kPa-1, an unprecedented sensing range, and robust mechanical and electrical performance. The aerogel sensors are demonstrated to monitor human motions, control robotic hands, and even integrate into a flexible keyboard to play music, which opens a wide application potential in future human-machine interfaces.

RESUMEN

The fundamental pathophysiological mechanism in the progression of chronic heart failure following acute myocardial infarction (AMI) is ventricular remodeling, in which innate and adaptive immunity both play critical roles. Myeloid-derived suppressor cells (MDSCs) have been demonstrated to function in a range of pathological conditions, such as infections, inflammation, autoimmune diseases, and tumors. However, it is unclear how MDSCs contribute to cardiac remodeling following AMI. This study aimed to identify the function and underlying mechanism of MDSCs in controlling cardiac remodeling following AMI. Following AMI in mice, MDSCs frequencies changed dynamically, considerably increased on day 7 in blood, spleens, lymph nodes and hearts, and decreased afterwards. Consistently, mice with AMI displayed enhanced cardiac function on day 14 post-AMI, reduced infract size and higher survival rates on day 28 post-AMI following the adoptive transfer of MDSCs. Furthermore, MDSCs inhibited the inflammatory response by decreasing pro-inflammatory cytokine (TNF-α, IL-17, Cxcl-1, and Cxcl-2) expression, up-regulating anti-inflammatory cytokine (TGF-ß1, IL-10, IL-4, and IL-13) expression, reducing CD3+ T cell infiltration in the infarcted heart and enhancing M2 macrophage polarization. Mechanistically, MDSCs improved the release of anti-inflammatory factors (TGF-ß1 and IL-10) and decreased the injury of LPS-induced cardiomyocytes in vitro in a manner dependent on cell-cell contact. Importantly, blockade of IL-10 partially abolished the cardioprotective role of MDSCs. This study found that MDSCs contributed to the restoration of cardiac function and alleviation of adverse cardiac remodeling after AMI possibly by inhibiting inflammation.

RESUMEN

Temporal proteomics data sets are often confounded by the challenges of missing values. These missing data points, in a time-series context, can lead to fluctuations in measurements or the omission of critical events, thus hindering the ability to fully comprehend the underlying biomedical processes. We introduce a Data Multiple Imputation (DMI) pipeline designed to address this challenge in temporal data set turnover rate quantifications, enabling robust downstream analysis to gain novel discoveries. To demonstrate its utility and generalizability, we applied this pipeline to two use cases: a murine cardiac temporal proteomics data set and a human plasma temporal proteomics data set, both aimed at examining protein turnover rates. This DMI pipeline significantly enhanced the detection of protein turnover rate in both data sets, and furthermore, the imputed data sets captured new representation of proteins, leading to an augmented view of biological pathways, protein complex dynamics, as well as biomarker-disease associations. Importantly, DMI exhibited superior performance in benchmark data sets compared to single imputation methods (DSI). In summary, we have demonstrated that this DMI pipeline is effective at overcoming challenges introduced by missing values in temporal proteome dynamics studies.

Asunto(s)

Proteoma , Proteómica , Humanos , Proteoma/análisis , Proteoma/metabolismo , Proteómica/métodos , Animales , Ratones , Estudios Longitudinales , Interpretación Estadística de Datos

RESUMEN

Secreted by natural killer cells and cytotoxic T lymphocytes, Granzyme B is involved in regulating the adaptive immune response in vertebrates and plays a pivotal role in resisting virus invasion and removing pathogens. Although it had been extensively studied in mammals, the involvement of Granzyme B in adaptive immune response of early vertebrates remained elusive. In this study, we investigated the Granzyme B in Oreochromis niloticus (OnGrB), found that its function domain was conserved. Additionally, OnGrB was widely expressed in various tissues and could respond to T-cell activation in vitro at the transcriptional level. Furthermore, we prepared the recombinant OnGrB (rOnGrB) as an immunogen to develop a mouse anti-OnGrB monoclonal antibody (mAb). Using this anti-OnGrB mAb as a tool, we explored the expression of OnGrB in the adaptive immune response of tilapia. Our findings revealed that T cell was a significant source of OnGrB production, the expression of OnGrB at the protein level and the proportion of OnGrB + T cells increased after both T cell activation in vitro and infection with Edwardsiella piscicida in vivo. More importantly, our findings also preliminarily illuminated that p65 could regulate the transcriptional activity of OnGrB. These results indicated that OnGrB was involved in the adaptive immunity of tilapia and played a critical role in T cell function in teleost. Our study provided theoretical support and new perspectives for understanding adaptive immunity in teleost.

Asunto(s)

Cíclidos , Edwardsiella , Infecciones por Enterobacteriaceae , Enfermedades de los Peces , Proteínas de Peces , Granzimas , Linfocitos T , Animales , Granzimas/genética , Granzimas/inmunología , Granzimas/metabolismo , Enfermedades de los Peces/inmunología , Proteínas de Peces/genética , Proteínas de Peces/inmunología , Cíclidos/inmunología , Cíclidos/genética , Edwardsiella/inmunología , Edwardsiella/fisiología , Infecciones por Enterobacteriaceae/inmunología , Infecciones por Enterobacteriaceae/veterinaria , Linfocitos T/inmunología , Inmunidad Adaptativa , Regulación de la Expresión Génica/inmunología , Secuencia de Aminoácidos , Alineación de Secuencia/veterinaria , Filogenia , Perfilación de la Expresión Génica/veterinaria

RESUMEN

As one of subunits for interleukin-2 receptor (IL-2R), CD122 can bind to IL-2 and then activate downstream signal transduction to participate in adaptive immune response. Although CD122 has been identified and investigated from several teleost species, studies on its function at T-cell level are still scarce for lack of specific antibodies. In this study, a typical CD122 in Nile tilapia (Oreochromis niloticus) was characterized by bioinformatics analysis, cloned to produce retrovirus infected NIH/3T3 cells for mouse immunization. After cell fusion and screening, we successfully developed a mouse anti-tilapia CD122 monoclonal antibody (mAb), which could specifically recognize CD122 and identify CD122-producing T cells of tilapia. Using the mAb to detect, CD122 was found to widely distribute in immune-related tissues, and significantly elevate post Edwardsiella piscicida infection or T-cell activation. More importantly, the expansion of CD122+ T cells and up-regulation of CD122 occurred both in total T cells and T-cell subsets during T-cell activation upon in vitro stimulation or in vivo infection. These results indicate that CD122 can be used as a T-cell activation marker in tilapia. Notably, CD122 mAb blocking blunted the activation of MAPK/Erk and mTORC1 pathways, and inhibited T-cell proliferation, suggesting a critical role of CD122 in ensuring proper proliferation of tilapia T cells. Therefore, this study enriches the knowledge of T-cell responses in fish and provides new evidence for understanding the evolution of lymphocyte-mediated adaptive immunity.

Asunto(s)

Cíclidos , Enfermedades de los Peces , Proteínas de Peces , Subunidad beta del Receptor de Interleucina-2 , Linfocitos T , Animales , Cíclidos/inmunología , Enfermedades de los Peces/inmunología , Proteínas de Peces/genética , Proteínas de Peces/inmunología , Linfocitos T/inmunología , Subunidad beta del Receptor de Interleucina-2/inmunología , Subunidad beta del Receptor de Interleucina-2/genética , Activación de Linfocitos , Infecciones por Enterobacteriaceae/inmunología , Infecciones por Enterobacteriaceae/veterinaria , Proliferación Celular/efectos de los fármacos , Filogenia , Ratones , Secuencia de Aminoácidos , Alineación de Secuencia/veterinaria , Biomarcadores

RESUMEN

Background: Different restoration materials have different optical characteristics that influence the intraoral scanner's (IOS) image accuracy. The purpose of this in-vitro investigation was to investigate how composite translucency affected the accuracy of IOS. Material and Methods: GC G-aenial Universal Injectable JE composite plates were used for the study at 3 thicknesses (1-2-3mm). A lab scanner (3Shape E1) obtained 1 reference scan, whereas IOS (Trios3) was used to conduct 10 experimental scans per group. After 3D superimposition, deviation values were used to assess the accuracy (trueness and precision) outcomes for the corresponding groups. Using an LS170 V2.0 colorimeter, the translucency parameter (TP) of the plates was determined from L*a*b* values of CIELAB color space. Results: The composite translucency resulted in a decrease in the scale of digital impressions. The 1mm group had the largest scale reduction (0.02mm) significantly, followed by the 2mm and 3mm groups (0.01mm). No difference was found in mean precision. The colorimeter detects the L*a*b* values and showed that 1mm composite plate expressed the highest TP value, then 2mm and 3mm groups (28.90, 14.26 and 6.49 respectively). The thinner composite, the higher translucency and TP were highly positively correlated to IOS trueness of composite plates. Conclusions: Composite translucency has an impact on optical impression accuracy. In correlation, the optical impression becomes less accurate the more translucent the composite is. This implies that in the digital process, the dentist should specify the appropriate optical properties of composite materials concerning both their mechanical and aesthetic qualities. Key words:Accuracy, translucency, resin composite, digital dentistry, intraoral-scanner.

RESUMEN

Purpose: This study aims to evaluate the predictive efficacy of the C-reactive protein/albumin ratio (CAR), a cost-effective, easily accessible, and reproducible biomarker obtained from standard blood tests, in forecasting acute kidney injury (AKI) among patients undergoing acute pancreatitis (AP). Considering that changes in the CAR are associated with AKI incidence in AP cases, this work aims to explore whether CAR can be used as the innovative, inflammation-based diagnostic marker for AKI in AP patients. Methods: The current retrospective cohort study consecutively enrolled AP patients admitted to First College of Clinical Medical Science of China Three Gorges University during the period from January 2019 to October 2023. Data were extracted systematically in electronic medical records from these hospitalized individuals, including baseline demographic and clinical characteristics. To ascertain the association of the CAR level with the development of AKI, we carried out multivariate logistic regression, adjusting for potential confounders. These confounders were initially identified through univariate regression. Furthermore, the potential effect modifiers in the relationship between CAR and AKI occurrence were explored by stratified logistic regression. Results: Totally, 1514 AP were recruited, including 257 (16.9%) with AKI. CAR was positively correlated with AKI. When adjusting for potential confounders, the AKI risk in patients in the upper CAR tertile (2.628-22.994) increased by 83% relative to those in lower tertile (0.05-0.289) (OR 1.83, 95% CI 1.13-2.96, P = 0.013). The AKI risk tended to increase according to the increasing CAR tertile (P for trend = 0.013). No significant interactions were observed among subgroups based on age, sex, BMI, admission to ICU, hypertension, DM, chronic obstructive pulmonary disease, severity of AP, etiology of AP, demand for CRRT, mechanical ventilation, and blood transfusion (all P > 0.05). Conclusion: A higher CAR is significantly related to the higher AKI incidence in AP patients in the Chinese population.

RESUMEN

INTRODUCTION: Trigeminal neuralgia (TN), marked by chronic pain from neural damage, is closely associated with inflammation. The role of OTULIN, a key regulator in inflammation and autophagy, is not fully understood in TN. The regulatory mechanism of OTULIN, a key protein involved in modulating inflammatory responses and autophagy processes, remains incompletely elucidated, particularly in the context of TN and neuroinflammation. METHODS: An infraorbital nerve ligation-induced rat model of TN was used. OTULIN's expression was modulated using adenovirus vectors and short hairpin RNA. The impact on pain and inflammatory responses was assessed via quantitative real-time polymerase chain reaction, western blot, immunofluorescence, and transcriptomic analysis. RESULTS: Enhanced OTULIN expression significantly increased head withdrawal thresholds and reduced pain sensitivity and neuroinflammatory markers in the model. Conversely, silencing OTULIN exacerbated pain and inflammation. Transcriptomic data revealed OTULINs influence on both inflammatory and autophagy pathways, specifically in suppressing NLR family pyrin domain containing 3 (NLRP3) inflammasome and promoting autophagy. In vitro experiments demonstrated OTULIN's inhibition of inflammatory markers in microglia and neurons. CONCLUSION: OTULIN is crucial in modulating TN, reducing neuropathic pain and neuroinflammation by activating the autophagy pathway and inhibiting the NLRP3 inflammasome.

Asunto(s)

Enfermedades Neuroinflamatorias , Ratas Sprague-Dawley , Neuralgia del Trigémino , Animales , Neuralgia del Trigémino/metabolismo , Ratas , Enfermedades Neuroinflamatorias/metabolismo , Masculino , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Autofagia/fisiología , Microglía/metabolismo , Inflamación/metabolismo

RESUMEN

Polymer-matrix composites have been widely used in the manufacture of seals, bearings, electrical insulators, and self-lubricating films as engineering applications move toward lighter weight, higher strength, and corrosion resistance. However, the high-speed shear effect of the friction pairs in relative motion leads to localized heating of the polymer surface, resulting in deformation or softening of the device. Herein, acer mono maple and canna leaves were used as templates to construct polymer-matrix sulfonated polyether-etherketone/polytetrafluoro-wax (SPEEK/PFW) composites with a surface-textured structure. As the bionic texture reduces the level of direct contact between the friction pairs, the frictional thermosoftening of SPEEK occurs in the localized areas of the bumps and leads to the release of PFW stored in textures, resulting in the formation of a soft polymer sliding layer in the worn area and greatly enhancing the frictional stability. By investigation of the tribological properties of textured SPEEK/PFW composites under different loads and sliding speeds, the mechanisms from surface wear to matrix softening and spontaneous construction of a slipping layer are summarized. The results of scanning electron microscopy and three-dimensional profilometer characterization of the wear scars show the surface state of SPEEK/PFW after friction, revealing the friction-thermotropic deformation of the surface texture. The results of this study not only improve our understanding of the frictional heat-induced surface self-lubrication mechanism of textured polymer composites but also provide a reference for the development of multiphase hybrid polymer-matrix composites with excellent self-lubrication properties.

RESUMEN

OBJECTIVES: To establish a reliable ultrasound (US) method of evaluating dynamic extrusion of lateral meniscus in healthy population, and to investigate the pattern of dynamic meniscus extrusion (ME) in lateral meniscus under loading conditions. METHODS: The lateral ME was examined via US method in unloaded, double-leg standing, and single-leg standing positions. Two different US measurement methods were compared to the magnetic resonance imaging (MRI) results to determine the optimal measurement methods. The US results obtained by different researchers were tested for interobserver consistency and the results obtained by the same researcher on two separate days were tested for intraobserver consistency. The patterns of dynamic extrusion were compared between medial and lateral sides. RESULTS: A total of healthy 44 volunteers were included in the study, with 86 knees assessed by US, and 25 knees evaluated by MRI. The US evaluation of dynamic lateral ME demonstrated excellent interobserver and intraobserver reliability. The US measurements using method A were consistent with the MRI results with no significant difference (P = .861, intraclass correlation coefficient [ICC] = 0.868), while method B underestimated the lateral ME compared to MRI (P = .001, ICC = 0.649). Lateral ME decreased slightly from unloaded (1.0 ± 0.8 mm) to single-leg standing position (0.8 ± 0.8 mm), whereas medial ME increased significantly in both double-leg and single-leg standing positions (2.4 ± 0.7 mm, 2.6 ± 0.7 mm). CONCLUSION: A novel US evaluation method of lateral ME was established with reliable and accurate results compared to the MRI. Lateral ME in healthy populations decreased slightly as the loadings increased, which was different from the pattern of dynamic extrusion in medial meniscus.

Asunto(s)

Meniscos Tibiales , Ultrasonografía , Humanos , Masculino , Femenino , Ultrasonografía/métodos , Adulto , Reproducibilidad de los Resultados , Meniscos Tibiales/diagnóstico por imagen , Valores de Referencia , Adulto Joven , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Variaciones Dependientes del Observador , Voluntarios Sanos

RESUMEN

The transforming growth factor beta-activated kinase 1 (TAK1)/c-Jun N-terminal kinase (JNK) axis is an essential MAPK upstream mediator and regulates immune signaling pathways. However, whether the TAK1/JNK axis harnesses the strength in regulation of signal transduction in early vertebrate adaptive immunity is unclear. In this study, by modeling on Nile tilapia (Oreochromis niloticus), we investigated the potential regulatory function of TAK1/JNK axis on lymphocyte-mediated adaptive immune response. Both OnTAK1 and OnJNK exhibited highly conserved sequences and structures relative to their counterparts in other vertebrates. Their mRNA was widely expressed in the immune-associated tissues, while phosphorylation levels in splenic lymphocytes were significantly enhanced on the 4th day post-infection by Edwardsiella piscicida. In addition, OnTAK1 and OnJNK were significantly up-regulated in transcriptional level after activation of lymphocytes in vitro by phorbol 12-myristate 13-acetate plus ionomycin (P + I) or PHA, accompanied by a predominant increase in phosphorylation level. More importantly, inhibition of OnTAK1 activity by specific inhibitor NG25 led to a significant decrease in the phosphorylation level of OnJNK. Furthermore, blocking the activity of OnJNK with specific inhibitor SP600125 resulted in a marked reduction in the expression of T-cell activation markers including IFN-γ, CD122, IL-2, and CD44 during PHA-induced T-cell activation. In summary, these findings indicated that the conserved TAK1/JNK axis in Nile tilapia was involved in adaptive immune responses by regulating the activation of lymphocytes. This study enriched the current knowledge of adaptive immunity in teleost and provided a new perspective for understanding the regulatory mechanism of fish immunity.

Asunto(s)

Inmunidad Adaptativa , Cíclidos , Enfermedades de los Peces , Proteínas de Peces , Activación de Linfocitos , Quinasas Quinasa Quinasa PAM , Animales , Cíclidos/inmunología , Cíclidos/genética , Proteínas de Peces/genética , Proteínas de Peces/inmunología , Enfermedades de los Peces/inmunología , Quinasas Quinasa Quinasa PAM/genética , Quinasas Quinasa Quinasa PAM/inmunología , Infecciones por Enterobacteriaceae/inmunología , Infecciones por Enterobacteriaceae/veterinaria , Edwardsiella/inmunología , Edwardsiella/fisiología , Regulación de la Expresión Génica/inmunología , Transducción de Señal/inmunología , Perfilación de la Expresión Génica/veterinaria , Filogenia , Alineación de Secuencia/veterinaria , Secuencia de Aminoácidos

RESUMEN

BACKGROUND: Diabetic wounds present significant challenges, specifically in terms of bacterial infection and delayed healing. Therefore, it is crucial to address local bacterial issues and promote accelerated wound healing. In this investigation, we utilized electrospinning to fabricate microgel/nanofiber membranes encapsulating MXene-encapsulated microgels and chitosan/gelatin polymers. RESULTS: The film dressing facilitates programmed photothermal therapy (PPT) and mild photothermal therapy (MPTT) under near-infrared (NIR), showcasing swift and extensive antibacterial and biofilm-disrupting capabilities. The PPT effect achieves prompt sterilization within 5 min at 52 °C and disperses mature biofilm within 10 min. Concurrently, by adjusting the NIR power to induce local mild heating (42 °C), the dressing stimulates fibroblast proliferation and migration, significantly enhancing vascularization. Moreover, in vivo experimentation successfully validates the film dressing, underscoring its immense potential in addressing the intricacies of diabetic wounds. CONCLUSIONS: The MXene microgel-loaded nanofiber dressing employs temperature-coordinated photothermal therapy, effectively amalgamating the advantageous features of high-temperature sterilization and low-temperature promotion of wound healing. It exhibits rapid, broad-spectrum antibacterial and biofilm-disrupting capabilities, exceptional biocompatibility, and noteworthy effects on promoting cell proliferation and vascularization. These results affirm the efficacy of our nanofiber dressing, highlighting its significant potential in addressing the challenge of diabetic wounds struggling to heal due to infection.

Asunto(s)

Antibacterianos , Vendajes , Nanofibras , Terapia Fototérmica , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Nanofibras/química , Terapia Fototérmica/métodos , Animales , Antibacterianos/farmacología , Antibacterianos/química , Ratones , Biopelículas/efectos de los fármacos , Quitosano/química , Masculino , Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Experimental/complicaciones , Temperatura , Ratas , Rayos Infrarrojos , Proliferación Celular/efectos de los fármacos , Ratas Sprague-Dawley , Humanos , Infección de Heridas/terapia

RESUMEN

The proficient handling of diabetic wounds, a rising issue coinciding with the global escalation of diabetes cases, poses significant clinical difficulties. A range of biofunctional dressings have been engineered and produced to expedite the healing process of diabetic wounds. This study proposes a multifunctional hydrogel dressing for diabetic wound healing, which is composed of Polyvinyl Alcohol (PVA) and N1-(4-boronobenzyl)-N3-(4-boronophenyl)-N1, N1, N3, N3-teramethylpropane-1, 3-diaminium (TSPBA), and a dual-drug loaded Gelatin methacryloyl (GM) microgel. The GM microgel is loaded with sodium fusidate (SF) and nanoliposomes (LP) that contain metformin hydrochloride (MH). Notably, adhesive and self-healing properties the hydrogel enhance their therapeutic potential and ease of application. In vitro assessments indicate that SF-infused hydrogel can eliminate more than 98% of bacteria within 24 h and maintain a sustained release over 15 days. Additionally, MH incorporated within the hydrogel has demonstrated effective glucose level regulation for a duration exceeding 15 days. The hydrogel demonstrates a sustained ability to neutralize ROS throughout the entire healing process, predominantly by electron donation and sequestration. This multifunctional hydrogel dressing, which integrated biological functions of efficient bactericidal activity against both MSSA and MRSA strains, blood glucose modulation, and control of active oxygen levels, has successfully promoted the healing of diabetic wounds in rats in 14 days. The hydrogel dressing exhibited significant effectiveness in facilitating the healing process of diabetic wounds, highlighting its considerable promise for clinical translation.

Asunto(s)

Antibacterianos , Vendajes , Hidrogeles , Alcohol Polivinílico , Especies Reactivas de Oxígeno , Cicatrización de Heridas , Animales , Cicatrización de Heridas/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología , Especies Reactivas de Oxígeno/metabolismo , Ratas , Antibacterianos/farmacología , Antibacterianos/química , Alcohol Polivinílico/química , Masculino , Hiperglucemia/tratamiento farmacológico , Diabetes Mellitus Experimental/complicaciones , Ratas Sprague-Dawley , Gelatina/química , Metformina/farmacología , Metformina/química , Liposomas/química , Staphylococcus aureus/efectos de los fármacos , Metacrilatos/química , Metacrilatos/farmacología , Adhesivos/química , Adhesivos/farmacología , Inyecciones

RESUMEN

Grooming, as an evolutionarily conserved repetitive behavior, is common in various animals, including humans, and serves essential functions including, but not limited to, hygiene maintenance, thermoregulation, de-arousal, stress reduction, and social behaviors. In rodents, grooming involves a patterned and sequenced structure, known as the syntactic chain with four phases that comprise repeated stereotyped movements happening in a cephalocaudal progression style, beginning from the nose to the face, to the head, and finally ending with body licking. The context-dependent occurrence of grooming behavior indicates its adaptive significance. This review briefly summarizes the neural substrates responsible for rodent grooming behavior and explores its relevance in rodent models of neuropsychiatric disorders and neurodegenerative diseases with aberrant grooming phenotypes. We further emphasize the utility of rodent grooming as a reliable measure of repetitive behavior in neuropsychiatric models, holding promise for translational psychiatry. Herein, we mainly focus on rodent self-grooming. Allogrooming (grooming being applied on one animal by its conspecifics via licking or carefully nibbling) and heterogrooming (a form of grooming behavior directing towards another animal, which occurs in other contexts, such as maternal, sexual, aggressive, or social behaviors) are not covered due to space constraints.

RESUMEN

Inherited non-hemolytic anemia is a group of rare bone marrow disorders characterized by erythroid defects. Although concerted efforts have been made to explore the underlying pathogenetic mechanisms of these diseases, the understanding of the causative mutations are still incomplete. Here we identify in a diseased pedigree that a gain-of-function mutation in toll-like receptor 8 (TLR8) is implicated in inherited non-hemolytic anemia. TLR8 is expressed in erythroid lineage and erythropoiesis is impaired by TLR8 activation whereas enhanced by TLR8 inhibition from erythroid progenitor stage. Mechanistically, TLR8 activation blocks annexin A2 (ANXA2)-mediated plasma membrane localization of STAT5 and disrupts EPO signaling in HuDEP2 cells. TLR8 inhibition improves erythropoiesis in RPS19+/- HuDEP2 cells and CD34+ cells from healthy donors and inherited non-hemolytic anemic patients. Collectively, we identify a gene implicated in inherited anemia and a previously undescribed role for TLR8 in erythropoiesis, which could potentially be explored for therapeutic benefit in inherited anemia.

Asunto(s)

Anemia , Eritropoyesis , Receptor Toll-Like 8 , Humanos , Eritropoyesis/genética , Receptor Toll-Like 8/metabolismo , Receptor Toll-Like 8/genética , Femenino , Anemia/genética , Masculino , Linaje , Eritropoyetina/metabolismo , Eritropoyetina/genética , Adulto , Transducción de Señal , Mutación , Células Eritroides/metabolismo , Animales , Células Precursoras Eritroides/metabolismo

RESUMEN

The Yangtze finless porpoise (YFP, Neophocaena asiaeorientalis asiaeorientalis) is the only freshwater cetacean found in China. However, per- and polyfluoroalkyl substances (PFASs) risks in YFPs remain unclear. In this study, legacy PFASs, their precursors and alternatives, were determined in YFP muscles (n = 32), liver (n = 29), kidney (n = 24), skin (n = 5), and blubbers (n = 25) collected from Poyang Lake (PL) and Yangtze River (YR) between 2017 and 2023. Perfluorooctane sulfonic acid (PFOS) was the predominant PFAS in all YFP tissues, with a median hepatic concentration of 1700 ng/g wet weight, which is higher than that in other finless porpoises worldwide. PFOS, chlorinated polyfluorinated ether sulfonates (Cl-PFESAs), and perfluoroalkane sulfonamides concentrations in YFP livers from PL were significantly higher than those from YR (p < 0.05); however, the opposite was observed for hexafluoropropylene oxide acids. Biomagnification and trophic magnification factors (BMF and TMF, respectively) of most PFASs in the YFP food web were > 1. Perfluoroheptane sulfonic acid had the highest BMF value (99), followed by 6:2 Cl-PFESA (94) and PFOS (81). The TMFmuscle and TMFliver values of the total PFASs were 3.4 and 6.6, respectively, and were significantly positively correlated with the fluorinated carbon chain length (p < 0.01). In addition, up to 62 % of the hazard quotients for 6:2 Cl-PFESA were > 1, which was higher than that of PFOS (48 %), suggesting a high hepatotoxicity of 6:2 Cl-PFESA to YFPs. Bioaccumulation and biotoxicity of legacy and emerging alternatives in aquatic organisms continue to be a concern, especially for underscoring the vulnerability of the long-lived and endangered species.

Asunto(s)

Fluorocarburos , Marsopas , Contaminantes Químicos del Agua , Animales , Marsopas/metabolismo , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidad , Medición de Riesgo , China , Fluorocarburos/análisis , Fluorocarburos/toxicidad , Monitoreo del Ambiente , Hígado/metabolismo , Cadena Alimentaria , Ríos/química , Lagos , Riñón/efectos de los fármacos , Riñón/metabolismo , Ácidos Alcanesulfónicos/análisis

RESUMEN

Chlorella has a variety of biological activities, and it is worth further exploring its pharmacological effects. In this study, we investigated the antioxidant and anti-ageing activities of Chlorella polysaccharide extract (CPE). Further studies revealed that CPE exhibited anti-ageing, and antioxidant activities in vivo, including an extended Caenorhabditis elegans stress resistance, decreased deposition of lipofuscin, and reduced effects of amyloid ß protein on mobility, decreased levels of reactive oxygen species and increased activity of antioxidant enzymes. Moreover, it dramatically increased the expression of anti-stress and longevity genes and reduced the expression of ageing-related genes; therefore, it was hypothesised that the mechanism of the age-delaying effect of CPE was related to the insulin signalling pathway. In summary, CPE could delay ageing and provide a new avenue for the application and development of CPE.

RESUMEN

Generation of hematopoietic stem and progenitor cells (HSPCs) ex vivo and in vivo, especially the generation of safe therapeutic HSPCs, still remains inefficient. In this study, we have identified compound BF170 hydrochloride as a previously unreported pro-hematopoiesis molecule, using the differentiation assays of primary zebrafish blastomere cell culture and mouse embryoid bodies (EBs), and we demonstrate that BF170 hydrochloride promoted definitive hematopoiesis in vivo. During zebrafish definitive hematopoiesis, BF170 hydrochloride increases blood flow, expands hemogenic endothelium (HE) cells and promotes HSPC emergence. Mechanistically, the primary cilia-Ca2+-Notch/NO signaling pathway, which is downstream of the blood flow, mediated the effects of BF170 hydrochloride on HSPC induction in vivo. Our findings, for the first time, reveal that BF170 hydrochloride is a compound that enhances HSPC induction and may be applied to the ex vivo expansion of HSPCs.

Asunto(s)

Diferenciación Celular , Hematopoyesis , Células Madre Hematopoyéticas , Pez Cebra , Animales , Células Madre Hematopoyéticas/efectos de los fármacos , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/metabolismo , Ratones , Diferenciación Celular/efectos de los fármacos , Hematopoyesis/efectos de los fármacos , Receptores Notch/metabolismo , Transducción de Señal/efectos de los fármacos , Cuerpos Embrioides/citología , Cuerpos Embrioides/efectos de los fármacos , Cuerpos Embrioides/metabolismo , Cilios/metabolismo , Cilios/efectos de los fármacos , Blastómeros/citología , Blastómeros/metabolismo , Blastómeros/efectos de los fármacos , Células Cultivadas

RESUMEN

BACKGROUND: Digenetic trematodes, including blood flukes, intestinal flukes, liver flukes, lung flukes, and pancreatic flukes, are highly diverse and distributed widely. They affect at least 200 million people worldwide, so better understanding of their global distribution and prevalence are crucial for controlling and preventing human trematodiosis. Hence, this scoping review aims to conduct a comprehensive investigation on the spatio-temporal distribution and epidemiology of some important zoonotic digenetic trematodes. METHODS: We conducted a scoping review by searching PubMed, Web of Science, Google Scholar, China National Knowledge Infrastructure, and Wanfang databases for articles, reviews, and case reports of zoonotic digenetic trematodes, without any restrictions on the year of publication. We followed the inclusion and exclusion criteria to identify relevant studies. And relevant information of the identified studies were collected and summarized. RESULTS: We identified a total of 470 articles that met the inclusion criteria and were included in the review finally. Our analysis revealed the prevalence and global distribution of species in Schistosoma, Echinostoma, Isthmiophora, Echinochasmus, Paragonimus, Opisthorchiidae, Fasciolidae, Heterophyidae, and Eurytrema. Although some flukes are distributed worldwide, developing countries in Asia and Africa are still the most prevalent areas. Furthermore, there were some overlaps between the distribution of zoonotic digenetic trematodes from the same genus, and the prevalence of some zoonotic digenetic trematodes was not entirely consistent with their global distribution. The temporal disparities in zoonotic digenetic trematodes may attribute to the environmental changes. The gaps in our knowledge of the epidemiology and control of zoonotic digenetic trematodes indicate the need for large cohort studies in most countries. CONCLUSIONS: This review provides important insights into the prevalence and global distribution of some zoonotic digenetic trematodes, firstly reveals spatio-temporal disparities in these digenetic trematodes. Countries with higher prevalence rate could be potential sources of transmitting diseases to other areas and are threat for possible outbreaks in the future. Therefore, continued global efforts to control and prevent human trematodiosis, and more international collaborations are necessary in the future.

Asunto(s)

Trematodos , Infecciones por Trematodos , Zoonosis , Animales , Zoonosis/epidemiología , Zoonosis/parasitología , Zoonosis/transmisión , Infecciones por Trematodos/epidemiología , Infecciones por Trematodos/parasitología , Humanos , Prevalencia , Salud Global