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Bovine tuberculosis (bTB), primarily caused by Mycobacterium bovis (M. bovis), is a globally zoonotic disease with significant economic impacts. Plasma exosomes have been extensively used for investigating disease processes and exploring biomarkers. While mass spectrometry (MS)-based proteomic analysis of plasma exosomes has been employed for human tuberculosis (TB) studies, it has not yet been applied to bTB. Therefore, a comprehensive proteomic overview of plasma exosomes from M. bovis-infected cows is essential. In this study, we presented an extensive proteomic analysis of plasma exosomes from 89 M. bovis-infected cows across three farms, using data dependent acquisition (DDA) mode. Our analysis encompasses 239,894 spectra, 6,011 peptides and 835 proteins. The proteomic overview revealed both consistencies and differences among individual cows, supplements 595 proteins to the bovine exosome library, and enriches tuberculosis and related pathways. Additionally, six pathways were validated as immune response pathways, and three proteins (CATHL1, H1-1, and LCN2) were identified as potential indicators of bTB. This study is the first to investigate the exosome proteome of plasma from cows infected with M. bovis, providing a valuable dataset for exploring candidate bTB markers and understanding the mechanisms of host defense against M. bovis.
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BACKGROUND: With aging, white adipose tissue (WAT) undergoes distribution change and browning inhibition, which could be attenuated by exercise. Adipokine chemerin exerts roles in the above changes of WAT, and our previous studies demonstrated the effect of decreased chemerin on exercise-induced improvement of glucose and lipid metabolism in high fat diet (HFD) feeding male mice, so this study is to clarify whether chemerin's effects on glucose and lipid metabolism are associated with the distribution and browning of WAT. METHODS: After diet and exercise interventions, body weight and adipose tissue contents in different depots of male mice were weighed, body composition and energy metabolism parameters were determined by Echo MRI Body Composition Analyzer and metabolic cage, respectively. The levels of serum adiponectin and leptin were detected by ELISA, and the protein levels of PGC-1α, UCP1, adiponectin and leptin in WAT were measured by Western blot. RESULTS: Chemerin knockout exacerbated HFD-induced weight gain, upregulated the increases of visceral and subcutaneous WAT (vWAT and sWAT, especial in sWAT), and inhibited WAT browning, but improved blood lipid. Exercise reduced the body weight and WAT distribution, increased sWAT browning and further improved blood lipid in aged HFD male mice, which were abrogated by chemerin knockout. Detrimental alterations of leptin, adiponectin and adiponectin/leptin ratio were discovered in the serum and WAT of aged HFD chemerin(-/-) mice; and exercise-induced beneficial changes in these adipokines were blocked by chemerin knockout. CONCLUSION: Chemerin influences blood lipid of aged male mice under HFD and exercise states through regulating the distribution and browning of WAT, which might be related to the changes of adiponectin, leptin and adiponectin/leptin ratio.
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Adiponectina , Tejido Adiposo Pardo , Tejido Adiposo Blanco , Quimiocinas , Dieta Alta en Grasa , Leptina , Ratones Noqueados , Condicionamiento Físico Animal , Animales , Masculino , Tejido Adiposo Blanco/metabolismo , Condicionamiento Físico Animal/fisiología , Quimiocinas/metabolismo , Quimiocinas/sangre , Ratones , Leptina/sangre , Leptina/metabolismo , Adiponectina/metabolismo , Adiponectina/sangre , Tejido Adiposo Pardo/metabolismo , Envejecimiento/metabolismo , Envejecimiento/fisiología , Lípidos/sangre , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Ratones Endogámicos C57BL , Metabolismo de los Lípidos/fisiología , Peso Corporal/fisiología , Metabolismo Energético/fisiología , Proteína Desacopladora 1/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismoRESUMEN
The practical application of aqueous zinc-ion batteries (ZIBs) indeed faces challenges primarily attributed to the inherent side reactions and dendrite growth associated with the Zn anode. In the present work, N-Methylmethanesulfonamide (NMS) is introduced to optimize the transfer, desolvation, and reduction of Zn2+, achieving highly stable and reversible Zn plating/stripping. The NMS molecule can substitute one H2O molecule in the solvation structure of hydrated Zn2+ and be preferentially chemisorbed on the Zn surface to protect Zn anode against corrosion and hydrogen evolution reaction (HER), thereby suppressing byproducts formation. Additionally, a robust N-rich organic and inorganic (ZnS and ZnCO3) hybrid solid electrolyte interphase is in situ generated on Zn anode due to the decomposition of NMS, resulting in enhanced Zn2+ transport kinetics and uniform Zn2+ deposition. Consequently, aqueous cells with the NMS achieve a long lifespan of 2300 h at 1 mA cm-2 and 1 mAh cm-2, high cumulative plated capacity of 3.25 Ah cm-2, and excellent reversibility with an average coulombic efficiency (CE) of 99.7% over 800 cycles.
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Multidrug-resistant (MDR) bacteria pose serious threats to public health due to the lack of effective and biocompatible drugs to kill MDR bacteria. Photodynamic antibacterial therapy has been widely studied due to its low induction of resistance. However, photosensitizers that can efficiently generate reactive oxygen species (ROS) through both type I and type II mechanisms and that have the capability of multiple modes of action are rarely reported. Addressing this issue, we developed a near-infrared-emitting triphenylamine indole iodoethane (TTII) and its silver(I) self-assembled (TTIIS) aggregation-induced emission (AIE) photosensitizer for multimode bacterial infection therapy. TTII can efficiently produce both Type I ROS â¢OH and Type II ROS 1O2. Interestingly, the Ag(I)-π interaction contributed in TTIIS efficiency promotion of the generation of 1O2. Moreover, by releasing Ag+, TTIIS enabled photodynamic-Ag(I) dual-mode sterilization. As a result, TTIIS achieved an effective enhancement of antibacterial activity, with a 1-2-fold boost against multidrug-resistant Escherichia coli (MDR E. coli). Both TTII and TTIIS at a concentration as low as 0.55 µg mL-1 can kill more than 98% of methicillin resistant Staphylococcus aureus (MRSA) on MRSA-infected full-thickness defect wounds of a mouse, and both TTII and TTIIS were effective in eliminating the bacteria and promoting wound healing.
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Antibacterianos , Farmacorresistencia Bacteriana Múltiple , Escherichia coli , Fármacos Fotosensibilizantes , Especies Reactivas de Oxígeno , Plata , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Plata/química , Plata/farmacología , Animales , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Ratones , Antibacterianos/farmacología , Antibacterianos/química , Escherichia coli/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Fotoquimioterapia , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacosRESUMEN
The adipokine chemerin contributes to exercise-induced improvements in glucose and lipid metabolism; however, the underlying mechanism remains unclear. We aimed to confirm the impact of reduced chemerin expression on exercise-induced improvement in glycolipid metabolism in male diabetic (DM) mice through exogenous chemerin administration. Furthermore, the underlying mechanism of chemerin involved in changes in muscle mitochondria function mediated by androgen/androgen receptor (AR) was explored by generating adipose-specific and global chemerin knockout (adipo-chemerin-/- and chemerin-/-) mice. DM mice were categorized into the DM, exercised DM (EDM), and EDM + chemerin supplementation groups. Adipo-chemerin-/- and chemerin-/- mice were classified in the sedentary or exercised groups and fed either a normal or high-fat diet. Exercise mice underwent a 6-wk aerobic exercise regimen. The serum testosterone and chemerin levels, glycolipid metabolism indices, mitochondrial function, and protein levels involved in mitochondrial biogenesis and dynamics were measured. Notably, exogenous chemerin reversed exercise-induced improvements in glycolipid metabolism, AR protein levels, mitochondrial biogenesis, and mitochondrial fusion in DM mice. Moreover, adipose-specific chemerin knockout improved glycolipid metabolism, enhanced exercise-induced increases in testosterone and AR levels in exercised mice, and alleviated the detrimental effects of a high-fat diet on mitochondrial morphology, biogenesis, and dynamics. Finally, similar improvements in glucose metabolism (but not lipid metabolism), mitochondrial function, and mitochondrial dynamics were observed in chemerin-/- mice. In conclusion, decreased chemerin levels affect exercise-induced improvements in glycolipid metabolism in male mice by increasing mitochondrial number and function, likely through changes in androgen/AR signaling.NEW & NOTEWORTHY Decreased chemerin levels affect exercise-induced improvements in glycolipid metabolism in male mice by increasing mitochondrial number and function, which is likely mediated by androgen/androgen receptor expression. This study is the first to report the regulatory mechanism of chemerin in muscle mitochondria.
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Quimiocinas , Glucosa , Metabolismo de los Lípidos , Ratones Noqueados , Receptores Androgénicos , Animales , Quimiocinas/metabolismo , Masculino , Ratones , Metabolismo de los Lípidos/fisiología , Metabolismo de los Lípidos/genética , Receptores Androgénicos/metabolismo , Receptores Androgénicos/genética , Glucosa/metabolismo , Dieta Alta en Grasa , Diabetes Mellitus Experimental/metabolismo , Péptidos y Proteínas de Señalización Intercelular/genética , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Condicionamiento Físico Animal/fisiología , Ratones Endogámicos C57BL , Mitocondrias Musculares/metabolismo , Mitocondrias/metabolismo , Andrógenos/metabolismo , Andrógenos/farmacología , Músculo Esquelético/metabolismoRESUMEN
Piezoelectric poly(vinylidene fluoride) (PVDF) and its copolymer, poly(vinylidene fluoride-co-trifluoroethylene) (P(VDF-TrFE)), have attracted considerable attention due to their potential in flexible, biocompatible energy harvesting and sensing devices. However, their limited piezoelectric performance hinders their widespread application. Inspired by the concept of morphotropic phase boundary (MPB) prevalent in high-performance piezoelectric ceramics, we successfully constructed MPB in the piezoelectric polymer P(VDF-TrFE) through size-dependent interface effects. We provided direct structural evidence using atomic force microscopy-infrared spectroscopy (AFM-IR) and significantly improved the piezoelectric performance of P(VDF-TrFE). The emergence of MPB is attributed to the interface effect induced by electrostatic interactions between ZnO fillers and the -CH2, -CF2, and -CHF groups in P(VDF-TrFE). This interaction drives a concomitant competition between the all-trans ß phase (normal ferroelectric) and the 3/1 helical phase (relaxor), resulting in enhanced piezoelectric responses in the transition region. By coupling the MPB effect with a porous structure, we developed a piezoelectric nanogenerator (PENG) that surpasses the electrical output limitation of current P(VDF-TrFE)-based PENGs. The fabricated PENG exhibits superior piezoelectric outputs (6.9 µW/cm2), impressive pressure sensitivity (2.3038 V/kPa), ultrafast response time (4.3 ms), and recovery time (46.4 ms)ânotably, without the need for additional poling treatment. In practical applications, the constructed PENG can efficiently generate characteristic signals in response to various human movements and harvest biomechanical energy. This work offers insight into utilizing interface-induced MPB and proposes a simple, scalable approach for developing high-performance self-polarized piezoelectric polymer films for self-powered sensing systems toward human-machine interaction.
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Hydraulic fracturing technology is the main method to develop low-permeability reservoirs. Fracture conductivity is not only the basis of fracture optimization design but also one of the key parameters to determine the effect of hydraulic fracturing. However, current methods of calculating fracture conductivity require a lot of time and labor cost. This research proposes a fracture conductivity prediction model based on machine learning. The main controlling factors of fracture conductivity are determined using the Pearson coefficient method and gray correlation analysis. Example application shows that the R2 values of the BP neural network model based on a genetic algorithm for predicting the fracture conductivity of block A and block B are 0.981 and 0.975, respectively, indicating that the machine learning model can accurately predict fracture conductivity.
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The current research on fracture conductivity ignores the placement of the proppant in fractures and relies on single-fracture conductivity testing and calculation, which cannot represent the overall conductivity of complex fracture systems. This research proposes a calculation method for the long-term conductivity of complex fractures based on proppant placement. This method considers fracture morphology, proppant placement, proppant embedment, and deformation under high closing pressure. The research results show that fracture conductivity decreases with increasing time, which can be divided into three stages: the embedding stage, the creep stage, and the stabilization stage. The long-term conductivity of the main fracture is higher than that of the branching fracture. With increasing closing pressure, the conductivities of both the main fracture and the branching fracture decrease. This is because increasing closure stress accelerates proppant embedment and creep, compressing the fluid flow space and further reducing fracture conductivity. Fracture conductivity is related to the placement of the proppant and sand concentration. Increasing the sand ratio can significantly increase the placement of the proppant in the main fracture and branching fractures, thereby improving fracture conductivity. Increasing the fracturing fluid viscosity can increase its proppant migration capacity. The proppant does not easily settle prematurely in high-viscosity fracturing fluid and can enter more into branching fractures, thereby improving their conductivity.
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Browning of white adipose tissue (WAT) is a focus of research in type 2 diabetes mellitus (T2DM) and metabolism, which may be a potential molecular mechanism for high-intensity interval training (HIIT) to improve T2DM. In this study, male C57BL/6J wild-type mice were subjected to an 8-week HIIT regimen following T2DM induction through a high-fat diet (HFD) combined with streptozotocin (STZ) injection. We found that HIIT improved glucose metabolism, body weight, and fat mass in T2DM mice. HIIT also decreased adipocyte size and induced browning of WAT. Our data revealed a decrease in TNFα and an increase in IL-10 with HIIT, although the expression of chemokines MCP-1 and CXCL14 was increased. We observed increased pan-macrophage infiltration induced by HIIT, along with a simultaneous decrease in the expression of M1 macrophage markers (iNOS and CD11c) and an increase in M2 macrophage markers (Arg1 and CD206), suggesting that HIIT promotes M2 macrophage polarization. Additionally, HIIT upregulated the expression of Slit3 and neurotrophic factors (BDNF and NGF). The expression of the sympathetic marker tyrosine hydroxylase (TH) and the nerve growth marker GAP43 was also increased, demonstrating the promotion of sympathetic nerve growth and density by HIIT. Notably, we observed macrophages co-localizing with TH, and HIIT induced the accumulation of M2 macrophages around sympathetic nerves, suggesting a potential association between M2 macrophages and increased density of sympathetic nerves. In conclusion, HIIT induces adipose tissue browning and improves glucose metabolism in T2DM mice by enhancing M2 macrophage polarization and promoting sympathetic nerve growth and density.
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Diabetes Mellitus Tipo 2 , Entrenamiento de Intervalos de Alta Intensidad , Masculino , Animales , Ratones , Diabetes Mellitus Tipo 2/metabolismo , Ratones Endogámicos C57BL , Tejido Adiposo/metabolismo , Macrófagos/metabolismo , Tejido Adiposo Blanco/metabolismo , Glucosa/metabolismo , Proteínas de la Membrana/metabolismoRESUMEN
Active pulmonary tuberculosis (PTB) poses challenges in rapid diagnosis within complex clinical conditions. Given the close association between neutrophils and tuberculosis, we explored differentially expressed long non-coding RNAs (lncRNAs) in neutrophils as potential molecular markers for diagnosing active PTB. We employed a gene microarray to screen for lncRNA alterations in neutrophil samples from three patients with active PTB and three healthy controls. The results revealed differential expression of 1457 lncRNAs between the two groups, with 916 lncRNAs upregulated and 541 lncRNAs down-regulated in tuberculosis patients. Subsequent validation tests demonstrated down-regulation of lncRNA ZNF100-6:2 in patients with active PTB, which was restored following anti-tuberculosis treatment. Our findings further indicated a high diagnostic potential for lncRNA ZNF100-6:2, as evidenced by an area under the receiver operating characteristic (ROC) curve of 0.9796 (95% confidence interval: 0.9479 to 1.000; P < 0.0001). This study proposes lncRNA ZNF100-6:2 as a promising and novel diagnostic biomarker for active PTB.
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ARN Largo no Codificante , Tuberculosis Pulmonar , Tuberculosis , Humanos , Biomarcadores , Neutrófilos , ARN Largo no Codificante/genética , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/genéticaRESUMEN
In this study, we synthesized a coumarin-hemicyanine-based deep red fluorescent dye that exhibits an intramolecular charge transfer (ICT). The probe had a large Stokes shift of 287 nm and a large molar absorption coefficient (ε = 7.5 × 105 L·mol-1·cm-1) and is best described as a deep red luminescent fluorescent probe with λem = 667 nm. The color of probe W changed significantly when it encountered cyanide ions (CN-). The absorption peak (585 nm) decreased gradually, and the absorption peak (428 nm) increased gradually, so that cyanide (CN-) could be identified by the naked eye. Moreover, an obvious fluorescence change was evident before and after the reaction under irradiation using 365 nm UV light. The maximum emission peak (667 nm) decreased gradually, whilst the emission peak (495 nm) increased gradually, which allowed for the proportional fluorescence detection of cyanide (CN-). Using fluorescence spectrometry, the fluorescent probe W could linearly detect CN- over the concentration range of 1-9 µM (R2 = 9913, RSD = 0.534) with a detection limit of 0.24 µM. Using UV-Vis spectrophotometry, the linear detection range for CN- was found to be 1-27 µM (R2 = 0.99583, RSD = 0.675) with a detection limit of 0.13 µM. The sensing mechanism was confirmed by 1H NMR spectroscopic titrations, 13C NMR spectroscopy, X-ray crystallographic analysis and HRMS. The recognition and detection of CN- by probe W was characterized by a rapid response, high selectivity, and high sensitivity. Therefore, this probe provides a convenient, effective and economical method for synthesizing and detecting cyanide efficiently and sensitively.
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Cianuros , Colorantes Fluorescentes , Cianuros/química , Colorantes Fluorescentes/química , Carbocianinas , Cumarinas/química , Espectrometría de Fluorescencia/métodosRESUMEN
The electrochemical properties of vanadium-based materials as cathode materials for aqueous zinc ion batteries are still restricted by low conductivity, sluggish reaction kinetics, and poor structural stability. Herein, the [VO6] octahedron, as the basic unit of vanadium-oxide layer of ammonium vanadates (NH4V4O10, denoted as NVO), is incorporated by F atoms to regulate the coordinated environment of vanadium. Density functional theory (DFT) calculations and experimental results show that both physicochemical and electrochemical properties of NVO are improved by F-doping. The enhanced electronic conductivity accelerates the electron transfer and the expanded interlayer spacing expedites the diffusion kinetics of zinc ions. As a result, the F-doped NVO (F-NVO) electrode shows a high discharge capacity (465 mAh g-1 at 0.1 A g-1), good rate capability (260 mAh g-1 at 5 A g-1), and long-term cycling stability (88% capacity retention over 2000 cycles at 4 A g-1). The reaction kinetics and energy storage mechanism of F-NVO are further validated by in situ and ex situ characterizations.
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Bacterial infections typically invade the living tissue of wounds, thereby aggravating the inflammatory response, delaying wound healing, or causing further complications. In this paper, the antibacterial hydrogel (PNVBA) with antifreezing and antidrying properties was prepared by a two-step method using N-isopropylacrylamide (NIPAM), 1-butyl-3-vinylimidazolium bromide (VBIMBr), and 3-acrylamidophenylboronic acid (AAPBA). PNVBA hydrogels exhibited a high adsorption capacity of 280 mg·g-1 for bovine serum albumin (BSA) and can adhere to the surface of different materials through ion-dipole or hydrogen-bonding interactions. Meanwhile, the PNVBA hydrogels exhibited high viscoelasticity and good adhesion after freezing at -20 °C or heating at 70 °C for 24 h with a sterilizing rate of up to 98% against multidrug-resistant (MDR) Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA). Moreover, a survival rate of up to 90% after incubation with L929 cells over 24 h was observed. Therefore, this inherent antibacterial hydrogel can be used as an excellent alternative material for wound dressings.
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Hidrogeles , Staphylococcus aureus Resistente a Meticilina , Hidrogeles/farmacología , Vendajes , Antibacterianos/farmacología , Escherichia coli , Polímeros/farmacologíaRESUMEN
Piezoelectric poly(vinylidene fluoride) (PVDF) and its copolymers have been widely investigated for applications in wearable electric devices and sensing systems, owing to their intrinsic piezoelectricity and superior flexibility. However, their weak piezoelectricity poses major challenges for practical applications. To overcome these challenges, we propose a two-step synthesis approach to fabricate sandwich-structured piezoelectric films (BaTiO3@PDA/PVDF/BaTiO3@PDA) with significantly enhanced ferroelectric and piezoelectric properties. As compared to pristine PVDF films or conventional 0-3 composite films, a maximum polarization (Pmax) of 11.24 µC/cm2, a remanent polarization (Pr) of 5.83 µC/cm2, and an enhanced piezoelectric coefficient (d33 â¼ 14.6 pC/N) were achieved. Simulation and experimental results have demonstrated that the sandwich structure enhances the ability of composite films to withstand higher poling electric fields in comparison with 0-3 composites. The sandwich-structured piezoelectric films are further integrated into a wireless sensor system with a high force sensitivity of 288 mV/N, demonstrating great potential for movement monitoring applications. This facile approach shows great promise for the large-scale production of composite films with remarkable flexibility, ferroelectricity, and piezoelectricity for wearable sensing devices.
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Glucagon-like peptide-1 (GLP-1), secreted by intestinal L-cells, plays a pivotal role in the modulation of ß-cell insulin secretion in a glucose-dependent manner, concurrently promoting ß-cell survival and ß-cell mass. Notably, GLP-1 has emerged as an effective second-line treatment for type 2 diabetes mellitus, gaining further prominence for its pronounced impact on body weight reduction, positioning it as a potent antiobesity agent. However, the mechanism by which GLP-1 improves obesity remains unclear. Some reports suggest that this mechanism may be associated with the regulation of adipokine synthesis within adipose tissue. Chemerin, a multifunctional adipokine and chemokine, has been identified as a pivotal player in adipocyte differentiation and the propagation of systemic inflammation, a hallmark of obesity. This review provides a comprehensive overview of the mechanisms by which GLP-1 and chemerin play crucial roles in obesity and obesity-related diseases. It discusses well-established aspects, such as their effects on food intake and glycolipid metabolism, as well as recent insights, including their influence on macrophage polarization and adipose tissue thermogenesis. GLP-1 has been shown to increase the population of anti-inflammatory M2 macrophages, promote brown adipose tissue thermogenesis, and induce the browning of white adipose tissue. In contrast, chemerin exhibits opposite effects in these processes. In addition, recent research findings have demonstrated the promising potential of GLP-1-based therapies in directly or indirectly regulating chemerin expression. In an intriguing reciprocal relationship, chemerin has also been newly identified as a negative regulator of GLP-1 in vivo. This review delineates the intricate interplay between GLP-1 and chemerin, unraveling their mutual inhibitory interactions. To the best of our knowledge, no previous reviews have focused on this specific topic, making this review particularly valuable in expanding our understanding of the endocrine mechanisms of obesity and providing potential strategies for the treatment of obesity and related diseases.
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Diabetes Mellitus Tipo 2 , Péptido 1 Similar al Glucagón , Humanos , Péptido 1 Similar al Glucagón/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Tejido Adiposo Pardo/metabolismo , Adipoquinas/metabolismoRESUMEN
The global incidence of dengue fever has gradually increased in recent years, posing a serious threat to human health. In the absence of specific anti-dengue drugs, understanding the interaction of Dengue virus (DENV) with the host is essential for the development of effective therapeutic measures. Autophagy is often activated during DENV infection to promote viral replication, but the mechanism of how DENV's own proteins induce autophagy has not been clarified. In this study, we first preliminarily identified DENV-2 NS1 as the most likely viral protein for DENV-2-induced autophagy with the help of molecular docking techniques. Further experimental results confirmed that DENV-2 NS1 regulates DENV-2 infection of HUVEC-induced autophagy through the AMPK/ERK/mTOR signaling pathway. Mechanistically, DENV-2 NS1 mainly interacted with AMPK by means of its Wing structural domain, and NS1 bound to all three structural domains on the AMPKα subunit. Finally, the experimental results showed that DENV-2 NS1 promoted the interaction between LKB1 and AMPKα1 and thus activated AMPK by both increasing the expression of LKB1 and binding LKB1. In conclusion, the results of this study revealed that DENV-2 NS1 protein served as a platform for the interaction between AMPK and LKB1 after DENV-2 infection with HUVEC, and pulled AMPK and LKB1 together to form a complex. LKB1 to form a complex, promoting LKB1 action on the kinase structural domain of AMPKα1, which in turn promotes phosphorylation of the Thr172 site on the AMPK kinase structural domain and activates AMPK, thereby positively regulating the AMPK/ERK/mTOR signaling pathway and inducing autophagy. The present discovery improves our understanding of DENV-2-induced host autophagy and contributes to the development of anti-dengue drugs.
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Virus del Dengue , Dengue , Humanos , Proteínas Quinasas Activadas por AMP/metabolismo , Autofagia , Virus del Dengue/fisiología , Simulación del Acoplamiento Molecular , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Proteínas no Estructurales Virales/metabolismoRESUMEN
Triboelectric nanogenerators (TENGs) are promising for a variety of applications that require a reliable output performance and stability. In this work, by utilizing the synergistic effect of lithium chloride (LiCl) and MXene, poly(vinyl alcohol) (PVA) based composite films with humidity-sensitive properties were prepared and employed as a friction layer to achieve self-powered TENGs with enhanced output performance under high humidity. The composite material demonstrates exceptional and stable output performance in the humidity range of 30-95% while exhibiting a strong linear correlation with increasing relative humidity (RH). At 95% RH, its short-circuit current increases up to 31.91 µA, which is three times the output of the TENG fabricated by PVA and PTFE (P-TENG). The rich hydroxyl group in PVA, the strong hygroscopicity of LiCl, and the microcapacitor network provided by MXene nanosheets significantly improve the water absorption capacity and surface roughness of the composite material, resulting in an excellent triboelectric output of TENG. Short-circuit current of the TENG in a wide range of RH (from 50% to 98%) responds very sensitively to humidity fluctuations in the environment and superior adsorption-desorption performance as humidity decreases. Furthermore, TENG regarded as a power supply in high humidity conditions was realized and it can light up 240 LEDs instantaneously with the transfer charge density of TENG reaching 194.37 µC m-2. This technology presents an effective method for stable energy harvesting and self-powered sensing in fog, the ocean, and other high-humidity environments.
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Anions play an indispensable role in the balance and regulation of the ecological environment and human health; however, excess anions can cause serious ecological and environment problems. Therefore, the detection and removal of excess anions in aqueous solution is not only a technological problem but also crucial for environmental protection. Herein, a set of water-soluble pyrene-based cationic fluorophores were synthesized, which exhibit high sensitivity for the detection of the anions BF4-, PF6-, and ClO4- via electrostatic interactions. Such fluorescent probes exhibit "turn-on" emission characteristics even at low concentrations of anions due to anion-π+ interactions. Moreover, these fluorescence probes act as efficient precipitating agents for the removal of the BF4-, PF6-, and ClO4- anions from an aqueous environment. This work opens up new avenues for future research on pyrene-based fluorophores as turn-on fluorescence probes for anion detection and as excellent precipitating agents in environmental settings.
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PURPOSE: To predict prognosis in HIV-negative cryptococcal meningitis (CM) patients by developing and validating a machine learning (ML) model. METHODS: This study involved 523 HIV-negative CM patients diagnosed between January 1, 1998, and August 31, 2022, by neurologists from 3 tertiary Chinese centers. Prognosis was evaluated at 10 weeks after the initiation of antifungal therapy. RESULTS: The final prediction model for HIV-negative CM patients comprised 8 variables: Cerebrospinal fluid (CSF) cryptococcal count, CSF white blood cell (WBC), altered mental status, hearing impairment, CSF chloride levels, CSF opening pressure (OP), aspartate aminotransferase levels at admission, and decreased rate of CSF cryptococcal count within 2 weeks after admission. The areas under the curve (AUCs) in the internal, temporal, and external validation sets were 0.87 (95% CI 0.794-0.944), 0.92 (95% CI 0.795-1.000), and 0.86 (95% CI 0.744-0.975), respectively. An artificial intelligence (AI) model was trained to detect and count cryptococci, and the mean average precision (mAP) was 0.993. CONCLUSION: A ML model for predicting prognosis in HIV-negative CM patients was built and validated, and the model might provide a reference for personalized treatment of HIV-negative CM patients. The change in the CSF cryptococcal count in the early phase of HIV-negative CM treatment can reflect the prognosis of the disease. In addition, utilizing AI to detect and count CSF cryptococci in HIV-negative CM patients can eliminate the interference of human factors in detecting cryptococci in CSF samples and reduce the workload of the examiner.
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Cryptococcus , Infecciones por VIH , Meningitis Criptocócica , Humanos , Meningitis Criptocócica/diagnóstico , Meningitis Criptocócica/tratamiento farmacológico , Inteligencia Artificial , Pronóstico , Aprendizaje Automático , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológicoRESUMEN
Background: Triple-negative breast cancer (TNBC) is an aggressive cancer that affects about 13/100,000 women yearly. Patients with TNBC are often resistant to endocrine and molecular targeted therapy, making clinical treatment challenging. Researches indicate that tumor microenvironment (TME) is related to prognosis in many cancers. Therefore, we aim to identify TME immune-related biomarkers to enhance the prognosis and immunotherapy efficacy in patients with TNBC. Methods: The bulk mRNA transcriptome data and clinical information of the (GSE58812) and (GSE25055) datasets were downloaded from the Gene Expression Omnibus (GEO) database, and the ESTIMATE algorithm was used to calculate the ImmuneScore, StromalScore, and ESTIMATEScore. Patients were divided into low and high groups according to the quartiles of ImmuneScore, StromalScore, and the median of ESTIMATEScore to filter differential expression genes (DEGs), respectively. The DEGs were then evaluated using univariate and multivariate Cox regression to identify TME-related genes and its association with survival rate for the construction of a TMErisk model with three biomarkers. Then Gene Expression Profiling Interactive Analysis (GEPIA) and The Cancer Genome Atlas (TCGA) data were used to compare the gene expression in cancer and normal tissues. xCell analysis calculated the proportion of tumor-infiltrating immune cells in low and high expression of ATPase Secretory Pathway Ca2+ Transporting 2 (ATP2C2). In addition, samples from 20 TNBC patients admitted to our institution were used for immunohistochemical (IHC) examination. Results: Three immune-related DEGs were identified, including prolyl 3-hydroxylase 2 (P3H2), sodium voltage-gated channel beta subunit 3 (SCN3B), and ATP2C2 and a TMErisk model was constructed and validated. However, only ATP2C2 was selected for further analysis. ATP2C2 mRNA level of TNBC patients was higher than that of normal breast tissue. Survival analysis showed that patients with high expression of ATP2C2 had a bad prognosis. xCell analysis demonstrated that the expression of ATP2C2 was associated with 16 kinds of tumor-infiltrating immune cells. Protein expression of ATP2C2 in TNBC tissues was higher compared to paired normal tissues in IHC. Conclusions: This study constructed and validated a TMErisk model that can effectively predict 3- and 5-year survival rate for TNBC patients. TNBC patients with lower expression of ATP2C2 had a good prognosis.