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The bone marrow adjusts blood cell production to meet physiological demands in response to insults. The spatial organization of normal and stress responses are unknown owing to the lack of methods to visualize most steps of blood production. Here we develop strategies to image multipotent haematopoiesis, erythropoiesis and lymphopoiesis in mice. We combine these with imaging of myelopoiesis1 to define the anatomy of normal and stress haematopoiesis. In the steady state, across the skeleton, single stem cells and multipotent progenitors distribute through the marrow enriched near megakaryocytes. Lineage-committed progenitors are recruited to blood vessels, where they contribute to lineage-specific microanatomical structures composed of progenitors and immature cells, which function as the production sites for each major blood lineage. This overall anatomy is resilient to insults, as it was maintained after haemorrhage, systemic bacterial infection and granulocyte colony-stimulating factor (G-CSF) treatment, and during ageing. Production sites enable haematopoietic plasticity as they differentially and selectively modulate their numbers and output in response to insults. We found that stress responses are variable across the skeleton: the tibia and the sternum respond in opposite ways to G-CSF, and the skull does not increase erythropoiesis after haemorrhage. Our studies enable in situ analyses of haematopoiesis, define the anatomy of normal and stress responses, identify discrete microanatomical production sites that confer plasticity to haematopoiesis, and uncover unprecedented heterogeneity of stress responses across the skeleton.
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Hematopoyesis , Células Madre Hematopoyéticas , Estrés Fisiológico , Animales , Femenino , Masculino , Ratones , Envejecimiento/fisiología , Infecciones Bacterianas/patología , Infecciones Bacterianas/fisiopatología , Vasos Sanguíneos/citología , Linaje de la Célula , Eritropoyesis , Factor Estimulante de Colonias de Granulocitos/metabolismo , Hematopoyesis/fisiología , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/metabolismo , Hemorragia/patología , Hemorragia/fisiopatología , Linfopoyesis , Megacariocitos/citología , Células Madre Multipotentes/citología , Células Madre Multipotentes/metabolismo , Mielopoyesis , Cráneo/irrigación sanguínea , Cráneo/patología , Cráneo/fisiopatología , Esternón/irrigación sanguínea , Esternón/citología , Esternón/metabolismo , Estrés Fisiológico/fisiología , Tibia/irrigación sanguínea , Tibia/citología , Tibia/metabolismoRESUMEN
Brown adipose tissue (BAT) is the main site of nonshivering thermogenesis which plays an important role in thermogenesis and energy metabolism. However, the regulatory factors that inhibit BAT activity remain largely unknown. Here, cardiotrophin-like cytokine factor 1 (CLCF1) is identified as a negative regulator of thermogenesis in BAT. Adenovirus-mediated overexpression of CLCF1 in BAT greatly impairs the thermogenic capacity of BAT and reduces the metabolic rate. Consistently, BAT-specific ablation of CLCF1 enhances the BAT function and energy expenditure under both thermoneutral and cold conditions. Mechanistically, adenylate cyclase 3 (ADCY3) is identified as a downstream target of CLCF1 to mediate its role in regulating thermogenesis. Furthermore, CLCF1 is identified to negatively regulate the PERK-ATF4 signaling axis to modulate the transcriptional activity of ADCY3, which activates the PKA substrate phosphorylation. Moreover, CLCF1 deletion in BAT protects the mice against diet-induced obesity by promoting BAT activation and further attenuating impaired glucose and lipid metabolism. Therefore, our results reveal the essential role of CLCF1 in regulating BAT thermogenesis and suggest that inhibiting CLCF1 signaling might be a potential therapeutic strategy for improving obesity-related metabolic disorders.
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Tejido Adiposo Pardo , Metabolismo Energético , Animales , Ratones , Adenoviridae , Interleucinas , Obesidad/genética , Termogénesis/genéticaRESUMEN
One of the prevalent chronic inflammatory disorders of the nasal mucosa, allergic rhinitis (AR) has become more widespread in recent years. Acupuncture pterygopalatine ganglion (aPPG) is an emerging alternative therapy that is used to treat AR, but the molecular mechanisms underlying its anti-inflammatory effects are unclear. This work methodically demonstrated the multi-target mechanisms of aPPG in treating AR based on bioinformatics/topology using techniques including text mining, bioinformatics, and network topology, among others. A total of 16 active biomarkers and 108 protein targets related to aPPG treatment of AR were obtained. A total of 345 Gene Ontology terms related to aPPG of AR were identified, and 135 pathways were screened based on Kyoto Encyclopedia of Genes and Genomes analysis. Our study revealed for the first time the multi-targeted mechanism of action of aPPG in the treatment of AR. In animal experiments, aPPG ameliorated rhinitis symptoms in OVA-induced AR rats; decreased serum immunoglobulin E, OVA-sIgE, and substance P levels; elevated serum neuropeptide Y levels; and modulated serum Th1/Th2/Treg/Th17 cytokine expression by a mechanism that may be related to the inhibition of activation of the TLR4/NF-κB/NLRP3 signaling pathway. In vivo animal experiments once again validated the results of the bioinformatics analysis. This study revealed a possible multi-target mechanism of action between aPPG and AR, provided new insights into the potential pathogenesis of AR, and proved that aPPG was a promising complementary alternative therapy for the treatment of AR.
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Terapia por Acupuntura , Biología Computacional , Rinitis Alérgica , Rinitis Alérgica/terapia , Rinitis Alérgica/metabolismo , Animales , Biología Computacional/métodos , Ratas , Ganglios Parasimpáticos/metabolismo , Masculino , Humanos , Mapas de Interacción de Proteínas , Citocinas/metabolismoRESUMEN
An outbreak of coronavirus disease 2019 (COVID-19)1-3, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)4, has spread globally. Countermeasures are needed to treat and prevent further dissemination of the virus. Here we report the isolation of two specific human monoclonal antibodies (termed CA1 and CB6) from a patient convalescing from COVID-19. CA1 and CB6 demonstrated potent SARS-CoV-2-specific neutralization activity in vitro. In addition, CB6 inhibited infection with SARS-CoV-2 in rhesus monkeys in both prophylactic and treatment settings. We also performed structural studies, which revealed that CB6 recognizes an epitope that overlaps with angiotensin-converting enzyme 2 (ACE2)-binding sites in the SARS-CoV-2 receptor-binding domain, and thereby interferes with virus-receptor interactions by both steric hindrance and direct competition for interface residues. Our results suggest that CB6 deserves further study as a candidate for translation to the clinic.
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Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Betacoronavirus/inmunología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Neumonía Viral/inmunología , Neumonía Viral/virología , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/inmunología , Enzima Convertidora de Angiotensina 2 , Animales , Anticuerpos Neutralizantes/química , Anticuerpos Neutralizantes/farmacología , Anticuerpos Antivirales/química , Anticuerpos Antivirales/farmacología , Betacoronavirus/química , Unión Competitiva , COVID-19 , Línea Celular , Chlorocebus aethiops , Cristalización , Cristalografía por Rayos X , Femenino , Humanos , Técnicas In Vitro , Macaca mulatta/inmunología , Macaca mulatta/virología , Masculino , Modelos Moleculares , Pruebas de Neutralización , Pandemias , Peptidil-Dipeptidasa A/química , Peptidil-Dipeptidasa A/metabolismo , Unión Proteica/efectos de los fármacos , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus/antagonistas & inhibidores , Glicoproteína de la Espiga del Coronavirus/metabolismo , Células Vero , Carga Viral/inmunologíaRESUMEN
The molecular clock that generates daily rhythms of behavior and physiology consists of interlocked transcription-translation feedback loops. In Drosophila, the primary feedback loop involving the CLOCK-CYCLE transcriptional activators and the PERIOD-TIMELESS transcriptional repressors is interlocked with a secondary loop involving VRILLE (VRI) and PAR DOMAIN PROTEIN 1 (PDP1), a repressor and activator of Clock transcription, respectively. Whereas extensive studies have found numerous transcriptional, translational, and posttranslational modulators of the primary loop, relatively little is known about the secondary loop. In this study, using male and female flies as well as cultured cells, we demonstrate that TARANIS (TARA), a Drosophila homolog of the TRIP-Br/SERTAD family of transcriptional coregulators, functions with VRI and PDP1 to modulate the circadian period and rhythm strength. Knocking down tara reduces rhythm amplitude and can shorten the period length, while overexpressing TARA lengthens the circadian period. Additionally, tara mutants exhibit reduced rhythmicity and lower expression of the PDF neuropeptide. We find that TARA can form a physical complex with VRI and PDP1, enhancing their repressor and activator functions, respectively. The conserved SERTA domain of TARA is required to regulate the transcriptional activity of VRI and PDP1, and its deletion leads to reduced locomotor rhythmicity. Consistent with TARA's role in enhancing VRI and PDP1 activity, overexpressing tara has a similar effect on the circadian period and rhythm strength as simultaneously overexpressing vri and Pdp1 Together, our results suggest that TARA modulates circadian behavior by enhancing the transcriptional activity of VRI and PDP1.
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Proteínas de Drosophila , Drosophila , Animales , Masculino , Femenino , Drosophila/fisiología , Retroalimentación , Proteínas de Drosophila/metabolismo , Ritmo Circadiano/genética , Proteínas CLOCK/genética , Drosophila melanogaster/metabolismoRESUMEN
Xanthomonas citri pv. citri (Xcc) causes the devastating citrus canker disease. Xcc is known to have been introduced into Florida, USA in at least three different events in 1915, 1986 and 1995 with the first two claimed to be eradicated. It was questioned whether the Xcc introduction in 1986 has been successfully eradicated. Furthermore, it is unknown how Xcc has spread throughout the citrus groves in Florida. In this study, we investigated the population structure of Xcc to address these questions. We sequenced the whole genome of 343 Xcc strains collected from Florida groves between 1997 and 2016. Our analysis revealed two distinct clusters of Xcc. Our data strongly indicate that the claimed eradication of the 1986 Xcc introduction was not successful and Xcc strains from 1986 introduction were present in samples from at least 8 counties collected after 1994. Importantly, our data revealed that the Cluster 2 strains, which are present in all 20 citrus-producing counties sampled in Florida, originated from the Xcc introduction event in the Miami area in 1995. Our data suggest that Polk County is the epicenter of the dispersal of Cluster 2 Xcc strains, which is consistent with the fact that three major hurricanes passed through Polk County in 2004. As copper-based products have been extensively used to control citrus canker, we also investigated whether Xcc strains have developed resistance to copper. Notably, none of the 343 strains contained known copper resistance genes. Twenty randomly selected Xcc strains displayed sensitivity to copper. Overall, this study provides valuable insights into the introduction, eradication, spread, and copper resistance of Xcc in Florida.
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Citrus , Xanthomonas , Cobre , Filogenia , Xanthomonas/genética , Enfermedades de las Plantas/genéticaRESUMEN
Pre-existing psychiatric disorders were linked to an increased susceptibility to COVID-19 during the initial outbreak of the pandemic, while evidence during Omicron prevalence is lacking. Leveraging data from two prospective cohorts in China, we identified incident Omicron infections between January 2023 and April 2023. Participants with a self-reported history or self-rated symptoms of depression or anxiety before the Omicron pandemic were considered the exposed group, whereas the others were considered unexposed. We employed multivariate logistic regression models to examine the association of pre-existing depression or anxiety with the risk of any or severe Omicron infection indexed by medical interventions or severe symptoms. Further, we stratified the analyses by polygenic risk scores (PRSs) for COVID-19 and repeated the analyses using the UK Biobank data. We included 10,802 individuals from the Chinese cohorts (mean age = 51.1 years, 45.6% male), among whom 7841 (72.6%) were identified as cases of Omicron infection. No association was found between any pre-existing depression or anxiety and the overall risk of Omicron infection (odds ratio [OR] =1.04, 95% confidence interval [CI] 0.95-1.14). However, positive associations were noted for severe Omicron infection, either as infections requiring medical interventions (1.26, 1.02-1.54) or with severe symptoms (≥3: 1.73, 1.51-1.97). We obtained comparable estimates when stratified by COVID-19 PRS level. Additionally, using clustering method, we identified eight distinct symptom patterns and found associations between pre-existing depression or anxiety and the patterns characterized by multiple or complex severe symptoms including cough and taste and smell decline (ORs = 1.42-2.35). The results of the UK Biobank analyses corroborated findings of the Chinese cohorts. In conclusion, pre-existing depression and anxiety was not associated with the risk of Omicron infection overall but an elevated risk of severe Omicron infection, supporting the continued efforts on monitoring and possible early intervention in this high-risk population during Omicron prevalence.
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In mammalian cells, histone deacetylase (HDAC) and Sirtuin (SIRT) are two families responsible for removing acetyl groups from acetylated proteins. Here, we describe protein deacetylation coupled with deacetylimination as a function of lysyl oxidase (LOX) family members. LOX-like 3 (Loxl3) associates with Stat3 in the nucleus to deacetylate and deacetyliminate Stat3 on multiple acetyl-lysine sites. Surprisingly, Loxl3 N-terminal scavenger receptor cysteine-rich (SRCR) repeats, rather than the C-terminal oxidase catalytic domain, represent the major deacetylase/deacetyliminase activity. Loxl3-mediated deacetylation/deacetylimination disrupts Stat3 dimerization, abolishes Stat3 transcription activity, and restricts cell proliferation. In Loxl3-/- mice, Stat3 is constitutively acetylated and naive CD4+ T cells are potentiated in Th17/Treg cell differentiation. When overexpressed, the SRCR repeats from other LOX family members can catalyze protein deacetylation/deacetylimination. Thus, our findings delineate a hitherto-unknown mechanism of protein deacetylation and deacetylimination catalyzed by lysyl oxidases.
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Aminoácido Oxidorreductasas/metabolismo , Linfocitos T CD4-Positivos/enzimología , Colitis/enzimología , Procesamiento Proteico-Postraduccional , Factor de Transcripción STAT3/metabolismo , Acetilación , Aminoácido Oxidorreductasas/deficiencia , Aminoácido Oxidorreductasas/genética , Animales , Linfocitos T CD4-Positivos/inmunología , Catálisis , Diferenciación Celular , Núcleo Celular/enzimología , Proliferación Celular , Colitis/genética , Colitis/inmunología , Modelos Animales de Enfermedad , Genotipo , Células HEK293 , Células HeLa , Humanos , Células MCF-7 , Ratones Endogámicos C57BL , Ratones Noqueados , Fenotipo , Dominios Proteicos , Multimerización de Proteína , Interferencia de ARN , Factor de Transcripción STAT3/genética , Linfocitos T Reguladores/enzimología , Linfocitos T Reguladores/inmunología , Células Th17/enzimología , Células Th17/inmunología , Transcripción Genética , TransfecciónRESUMEN
BACKGROUND AND AIMS: Variants in ZFYVE19 underlie a disorder characterised by progressive portal fibrosis, portal hypertension and eventual liver decompensation. We aim to create an animal model to elucidate the pathogenic mechanism. METHODS: Zfyve19 knockout (Zfyve19-/- ) mice were generated and exposed to different liver toxins. Their livers were characterised at the tissue, cellular and molecular levels. Findings were compared with those in wild-type mice and in ZFYVE19-deficient patients. ZFYVE19 knockout and knockdown retinal pigment epithelial-1 cells and mouse embryonic fibroblasts were generated to study cell division and cell death. RESULTS: The Zfyve19-/- mice were normal overall, particularly with respect to hepatobiliary features. However, when challenged with α-naphthyl isothiocyanate, Zfyve19-/- mice developed changes resembling those in ZFYVE19-deficient patients, including elevated serum liver injury markers, increased numbers of bile duct profiles with abnormal cholangiocyte polarity and biliary fibrosis. Failure of cell division, centriole and cilia abnormalities, and increased cell death were observed in knockdown/knockout cells. Increased cell death and altered mRNA expression of cell death-related signalling pathways was demonstrated in livers from Zfyve19-/- mice and patients. Transforming growth factor-ß (TGF-ß) and Janus kinase-Signal Transducer and Activator of Transcription 3 (JAK-STAT3) signalling pathways were upregulated in vivo, as were chemokines such as C-X-C motif ligands 1, 10 and 12. CONCLUSIONS: Our findings demonstrated that ZFYVE19 deficiency is a ciliopathy with novel histological features. Failure of cell division with ciliary abnormalities and cell death activates macrophages and may thus lead to biliary fibrosis via TGF-ß pathway in the disease.
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Muerte Celular , Ciliopatías , Ratones Noqueados , Animales , Humanos , Ratones , Muerte Celular/genética , División Celular/genética , Cilios/patología , Cilios/genética , Cilios/metabolismo , Ciliopatías/genética , Ciliopatías/patología , Modelos Animales de Enfermedad , Hígado/patología , Hígado/metabolismo , Transducción de Señal/genéticaRESUMEN
The imaginary Poynting momentum (IPM) of light has been captivated as an unusual origin of optical forces. However, the IPM force is predicted only for dipolar magnetoelectric particles that are hardly used in optical manipulation experiments. Here, we report a whole family of high-order IPM forces for not only magnetoelectric but also generic Mie particles, assisted with their excited higher multipoles within. Such optomechanical manifestations derive from a nonlocal contribution of the IPM to the optical force, which can be remarkable even when the incident IPM is small. We observe the high-order optomechanics in a structured light beam, which, despite carrying no angular momentum, is able to set normal microparticles into continuous rotation. Our results provide unambiguous evidence of the ponderomotive nature of the IPM, expand the classification of optical forces, and open new possibilities for levitated optomechanics and micromanipulations.
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Mosquito-borne flaviviruses (MBFs) adapt to a dual-host transmission circle between mosquitoes and vertebrates. Dual-host affiliated insect-specific flaviviruses (dISFs), discovered from mosquitoes, are phylogenetically similar to MBFs but do not infect vertebrates. Thus, dISFMBF chimeras could be an ideal model to study the dual-host adaptation of MBFs. Using the pseudoinfectious reporter virus particle and reverse genetics systems, we found dISFs entered vertebrate cells as efficiently as the MBFs but failed to initiate replication. Exchange of the untranslational regions (UTRs) of Donggang virus (DONV), a dISF, with those from Zika virus (ZIKV) rescued DONV replication in vertebrate cells, and critical secondary RNA structures were further mapped. Essential UTR-binding host factors were screened for ZIKV replication in vertebrate cells, displaying different binding patterns. Therefore, our data demonstrate a post-entry cross-species transmission mechanism of MBFs, while UTR-host interaction is critical for dual-host adaptation.
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Culicidae , Flavivirus , Infección por el Virus Zika , Virus Zika , Animales , Adaptación al Huésped , Mosquitos Vectores , Replicación ViralRESUMEN
Many studies have indicated that tumor growth factor-beta (TGF-ß) signaling mediates radiation-induced bystander effects (RIBEs). The primary cilium (PC) coordinates several signaling pathways including TGF-ß signaling to regulate diverse cellular processes. But whether the PC participates in TGF-ß induced RIBEs remains unclear. The cellular levels of TGF-ß1 were detected by western blot analysis and the secretion of TGF-ß1 was measured by ELISA kit. The ciliogenesis was altered by CytoD treatment, STIL siRNA transfection, IFT88 siRNA transfection, or KIF3a siRNA transfection, separately, and was detected by western blot analysis and immunofluorescence staining. G0 /G1 phase cells were arrested by serum starvation and S phase cells were induced by double thymidine block. The TGF-ß1 signaling was interfered by LY2109761, a TGF-ß receptor 1 (TßR1) inhibitor, or TGF-ß1 neutral antibody. The DNA damages were induced by TGF-ß1 or radiated conditional medium (RCM) from irradiated cells and were reflected by p21 expression, 53BP1 foci, and γH2AX foci. Compared with unirradiated control, both A549 and Beas-2B cells expressed and secreted more TGF-ß1 after carbon ion beam or X-ray irradiation. RCM collected from irradiated cells or TGF-ß1 treatment caused an increase of DNA damage in cocultured unirradiated Beas-2B cells while blockage of TGF-ß signaling by TßR1 inhibitor or TGF-ß1 neutral antibody alleviates this phenomenon. IFT88 siRNA or KIF3a siRNA impaired PC formation resulted in an aggravated DNA damage in bystander cells, while elevated PC formation by CytoD or STIL siRNA resulted in a decrease of DNA damage. Furthermore, TGF-ß1 induced more DNA damages in S phases cells which showed lower PC formation rate and less DNA damages in G0 /G1 phase cells which showed higher PC formation rate. This study demonstrates the particular role of primary cilia during RCM induced DNA damages through TGF-ß1 signaling restriction and thereby provides a functional link between primary cilia and RIBEs.
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Efecto Espectador , Factor de Crecimiento Transformador beta1 , Efecto Espectador/genética , Efecto Espectador/efectos de la radiación , Cilios/metabolismo , ADN , ARN Interferente Pequeño/genética , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Humanos , Línea Celular TumoralRESUMEN
BACKGROUND: Interferon-gamma release assays (IGRA) are widely used for diagnosis of latent tuberculosis infection. However, with repeat testing, IGRA transformation (conversion or reversion) may be detected and is challenging to interpret. We reviewed the frequency of and risk factors for IGRA transformation. METHODS: We screened public databases for studies of human participants that reported the frequency of IGRA transformation. We extracted study and subject characteristics, details of IGRA testing and results. We calculated the pooled frequency of IGRA transformation (and transient transformation) and examined associated risk factors. RESULTS: The pooled frequency of IGRA conversion or reversion from 244 studies was estimated at 7.3% (95% CI 6.1-8.5%) or 22.8% (20.1-25.7%), respectively. Transient conversion or reversion were estimated at 46.0% (35.7-56.4%) or 19.6% (9.2-31.7%) of conversion or reversion events respectively. Indeterminate results seldom reverted to positive (1.2% [0.1-3.5%]). IGRA results in the borderline positive or negative range were associated with increased risk of conversion or reversion (pooled OR: conversion, 4.15 [3.00-5.30]; reversion, 4.06 [3.07-5.06]). BCG vaccination was associated with decreased risk of conversion (0.70, 0.56-0.84), cigarette smoking with decreased risk of reversion (0.44, 0.06-0.82), and female sex with decreased risk of either conversion or reversion (conversion, 0.66 [0.58-0.75]; reversion, 0.46 [0.31-0.61]). CONCLUSIONS: IGRA conversion is less common than reversion, and frequently transient. Research is needed to determine whether individuals with reversion would benefit from tuberculosis preventive treatment. Re-testing of people with indeterminate results is probably not indicated, since indeterminate results seldom revert to positive.
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Zinc-iodine batteries are one of the most intriguing types of batteries that offer high energy density and low toxicity. However, the low intrinsic conductivity of iodine, together with high polyiodide solubility in aqueous electrolytes limits the development of high-areal-capacity zinc-iodine batteries with high stability, especially at low current densities. Herein, we proposed a hydrophobic polyiodide ionic liquid as a zinc-ion battery cathode, which successfully activates the iodine redox process by offering 4 orders of magnitude higher intrinsic electrical conductivity and remarkably lower solubility that suppressed the polyiodide shuttle in a dual-plating zinc-iodine cell. By the molecular engineering of the chemical structure of the polyiodide ionic liquid, the electronic conductivity can reach 3.4 × 10-3 S cm-1 with a high Coulombic efficiency of 98.2%. The areal capacity of the zinc-iodine battery can achieve 5.04 mAh cm-2 and stably operate at 3.12 mAh cm-2 for over 990 h. Besides, a laser-scribing designed flexible dual-plating-type microbattery based on a polyiodide ionic liquid cathode also exhibits stable cycling in both a single cell and 4 × 4 integrated cell, which can operate with the polarity-switching model with high stability.
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Cholestatic liver diseases (CLD) are characterized by impaired normal bile flow, culminating in excessive accumulation of toxic bile acids. The majority of patients with CLD ultimately progress to liver cirrhosis and hepatic failure, necessitating liver transplantation due to the lack of effective treatment. Recent investigations have underscored the pivotal role of the gut microbiota-bile acid axis in the progression of hepatic fibrosis via various pathways. The obstruction of bile drainage can induce gut microbiota dysbiosis and disrupt the intestinal mucosal barrier, leading to bacteria translocation. The microbial translocation activates the immune response and promotes liver fibrosis progression. The identification of therapeutic targets for modulating the gut microbiota-bile acid axis represents a promising strategy to ameliorate or perhaps reverse liver fibrosis in CLD. This review focuses on the mechanisms in the gut microbiota-bile acids axis in CLD and highlights potential therapeutic targets, aiming to lay a foundation for innovative treatment approaches.
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Ácidos y Sales Biliares , Colestasis , Disbiosis , Microbioma Gastrointestinal , Humanos , Ácidos y Sales Biliares/metabolismo , Animales , Colestasis/metabolismo , Colestasis/microbiología , Hepatopatías/metabolismo , Hepatopatías/microbiología , Hepatopatías/etiología , Cirrosis Hepática/metabolismo , Cirrosis Hepática/microbiologíaRESUMEN
Glycerol tributyrate as a low-density lipoprotein plays a crucial role in drug development and food safety. In this work, a novel high-stability fiber optic sensor for glyceryl tributyrate based on the poly(acrylic acid) (PAA) and chitosan (CS) composite hydrogel embedding method is first proposed. Compared with traditional functionalization, the lipase in a polymer network structure used in this article can not only avoid chemical reactions that cause damage to the enzyme structure but also avoid the instability of ionic bonds and physical adsorption. Therefore, the PAA/CS hydrogel method proposed in this article can effectively retain enzyme structure. First, the impact of different layers (one to five layers) of PAA/CS on pH sensing performance was explored, and it was determined that layers 1-3 could be used for subsequent sensing experiments. Within the linear detection range of 0.5-10 mM, the detection sensitivities of the one to three layers of the biosensor are divided into 0.65, 0.95, and 1.51 nm/mM, respectively, with the three layers having the best effect. When the number of coating layers is three, the detection limit of the sensor is 0.47 mM, meeting the millimole level detection standard for anticancer requirement. Furthermore, the stability and selectivity of the sensor (in the presence of hemoglobin, urea, cholesterol, acetylcholine, and glucose) were analyzed. The three-layer sensor is used for sample detection. At concentrations of 1-10 mM, the absolute value of the recovery percentage (%) is 82-99%, which can accurately detect samples. The sensor proposed in this paper has the advantages of low sample consumption, high sensitivity, simple structure, and label-free measurement. The enzyme-embedding method provides a new route for rapid and reliable glyceryl tributyrate detection, which has potential applications in food safety as well as the development of anticancer drugs.
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Resinas Acrílicas , Quitosano , Fibras Ópticas , Resonancia por Plasmón de Superficie , Resinas Acrílicas/química , Quitosano/química , Hidrogeles/química , Límite de Detección , Lipasa/química , Lipasa/metabolismo , Técnicas Biosensibles/métodosRESUMEN
Aphrocallistes vastus lectin (AVL) is a Ca2+ dependent C-type lectin produced by sponges. Previous studies have demonstrated that oncolytic vaccinia virus harboring AVL (oncoVV-AVL) effectively triggers cell death in various tumors. However, the effects of oncoVV-AVL on human ovarian cancer (OV) remain unknown. This study aims to investigate the mechanism-of-action of oncoVV-AVL in human OV cell lines and in tumor-bearing nude mice. We found that oncoVV-AVL could directly induce apoptosis and autophagy in ovarian cancer cells. Additionally, our results showed that oncoVV-AVL increased the serum levels of mouse IFN-γ (mIFN-γ), leading to the activation of M1-polarized macrophages. Conversely, NADPH, a reducing agent by providing reducing equivalents, reduced the production of mIFN-γ, and suppressed M1-polarization of macrophage. Based on these findings, we propose that oncoVV-AVL not only contributes to direct cytolysis, but also enhances host immune response by promoting ROS levels.
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Traditional electromagnetic absorbing materials (EWAMs) are usually single functions and can easily affect their performance in diverse application scenarios. Effective integration of EWAMs into multiple function components is a valuable strategy to achieve maximum absorption and multifunction performance while maintaining their indispensable physical and chemical properties. In this work, the polyoxometalates (POMs) serving as "guests" are embedded within the Co-MOFs to construct 3d/4d-bimetallic based crystalline precursors of dielectric/magnetic synergistic system. The proper pyrolysis temperature induced the homogeneously distributed metallic Co and MoCx hetero-units into carbon matrix with modified porous defect engineering to enhance electromagnetic wave (EW). Owing to the brilliant synergistic effect of polarization, magnetic loss, and impedance matching, the superior RLmin of -47.72 dB at 11.76 GHz at the thickness of 2.0 mm and a wide adequate absorption bandwidth (EAB) of 4.58 GHz (7.44-12.02 GHz) covered the whole X-band at the thickness of 2.5 mm for η-MoC/Co@NC-800 are observed. More importantly, the resulting MoCx hybrid polyimide (MCP) aerogel exhibits desirable properties such as structural robustness, nonflammability, excellent thermal insulation, and self-cleaning capabilities that are comparable to those of commercially available products. This work offers inspiration and strategy for creating multipurpose microwave absorbers with intricate structural designs.
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Enantiomers (opposite chiral molecules) usually exhibit different effects when interacting with chiral agents, thus the identification and separation of enantiomers are of importance in pharmaceuticals and agrochemicals. Here an optical approach is proposed to enantioselective trapping of multiple pairs of enantiomers by a focused hybrid polarized beam. Numerical results indicate that such a focused beam shows multiple local optical chirality of opposite signs in the focal plane, and can trap the corresponding enantiomers near the extreme value of optical chirality density according to the handedness of enantiomers. The number and positions of trapped enantiomers can be changed by altering the value and sign of polarization orders of hybrid polarized beams, respectively. The key to realizing enantioselective optical trapping of enantiomers is that the chiral optical force exerted on enantiomers in this focused field is stronger than the achiral optical force. The results provide insight into the optical identification and separation of multiple pairs of enantiomers and will find applications in chiral detection and sensing.
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Lithium (Li) metal batteries are deemed as promising next-generation power solutions but are hindered by the uncontrolled dendrite growth and infinite volume change of Li anodes. The extensively studied 3D scaffolds as solutions generally lead to undesired "top-growth" of Li due to their high electrical conductivity and the lack of ion-transporting pathways. Here, by reducing electrical conductivity and increasing the ionic conductivity of the scaffold, the deposition spot of Li to the bottom of the scaffold can be regulated, thus resulting in a safe bottom-up plating mode of the Li and dendrite-free Li deposition. The resulting symmetrical cells with these scaffolds, despite with a limited pre-plated Li capacity of 5 mAh cm-2, exhibit ultra-stable Li plating/stripping for over 1 year (11 000 h) at a high current density of 3 mA cm-2 and a high areal capacity of 3 mAh cm-2. Moreover, the full cells with these scaffolds further demonstrate high cycling stability under challenging conditions, including high cathode loading of 21.6 mg cm-2, low negative-to-positive ratio of 1.6, and limited electrolyte-to-capacity ratio of 4.2 g Ah-1.