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Toxoplasma gondii is an opportunistic and pathogenic obligate intracellular parasitic protozoan that is widespread worldwide and can infect most warm-blooded animals, seriously endangering human health and affecting livestock production. Toxoplasmosis caused by T. gondii infection has different clinical manifestations, which are mainly determined by the virulence of T. gondii and host differences. Among the manifestations of this condition, abortion, stillbirth, and fetal malformation can occur if a woman is infected with T. gondii in early pregnancy. Here, we discuss how the T. gondii rhoptry protein affects host pregnancy outcomes and speculate on the related signaling pathways involved. The effects of rhoptry proteins of T. gondii on the placental barrier are complex. Rhoptry proteins not only regulate interferon-regulated genes (IRGs) to ensure the survival of parasites in activated cells but also promote the spread of worms in tissues and the invasive ability of the parasites. The functions of these rhoptry proteins and the associated signaling pathways highlight relevant mechanisms by which Toxoplasma crosses the placental barrier and influences fetal development and will guide future studies to uncover the complexity of the host-pathogen interactions.
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Placenta , Proteínas Protozoarias , Transducción de Señal , Toxoplasma , Toxoplasmosis , Femenino , Placenta/parasitología , Embarazo , Toxoplasma/fisiología , Animales , Humanos , Toxoplasmosis/parasitología , Complicaciones Parasitarias del Embarazo/parasitologíaRESUMEN
One of the common illnesses that affect women's physical and mental health is urinary tract infection (UTI). The disappointing results of empirical anti-infective treatment and the lengthy time required for urine bacterial culture are two issues. Antibiotic misuse is common, especially in females who experience recurrent UTI (rUTI). This leads to a higher prevalence of antibiotic resistance in the microorganisms that cause the infection. Antibiotic therapy will face major challenges in the future, prompting clinicians to update their practices. New testing techniques are making the potential association between the urogenital microbiota and UTIs increasingly apparent. Monitoring changes in female urinary tract (UT) microbiota, as well as metabolites, may be useful in exploring newer preventive treatments for UTIs. This review focuses on advances in urogenital microbiology and organismal metabolites relevant to the identification and handling of UTIs in an attempt to provide novel methods for the identification and management of infections of the UT. Particular attention is paid to the microbiota and metabolites in the patient's urine in relation to their role in supporting host health.
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Infecciones Urinarias , Sistema Urinario , Femenino , Humanos , Infecciones Urinarias/etiología , Antibacterianos/uso terapéutico , Sistema Urogenital , UrinálisisRESUMEN
Cells are the smallest units that make up living organisms, which constantly undergo the processes of proliferation, differentiation, senescence and death. Dead cells need to be removed in time to maintain the homeostasis of the organism and keep it healthy. This process is called efferocytosis. If the process fails, this may cause different types of diseases. More and more evidence suggests that a faulty efferocytosis process is closely related to the pathological processes of respiratory diseases. In this review, we will first introduce the process and the related mechanisms of efferocytosis of the macrophage. Secondly, we will propose some methods that can regulate the function of efferocytosis at different stages of the process. Next, we will discuss the role of efferocytosis in different lung diseases and the related treatment approaches. Finally, we will summarize the drugs that have been applied in clinical practice that can act upon efferocytosis, in order to provide new ideas for the treatment of lung diseases.
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Enfermedades Pulmonares , Trastornos Respiratorios , Humanos , Apoptosis/fisiología , Fagocitosis/fisiología , Macrófagos , Fagocitos/fisiologíaRESUMEN
We demonstrate the construction of heterojunction arrays for boosting solar water splitting by combining in situ guided growth of heterointerfaces and energy band tuning. By directly growing an ultrathin Fe2WO6 layer on a preformed WO3 nanosheet array in full coverage, a uniform and dense array of intimately contacted WO3/Fe2WO6 heterojunction was created. The heterojunction array shows not only a largely broadened visible light absorption range but also a built-in interface polarization to accelerate hole transfer from WO3 to Fe2WO6. Meanwhile, fine-tuning to match energy levels at the heterojunction was achieved by doping WO3 with Fe (Fe-WO3), leading to improved electrical conductivity and reduced charge recombination. Photoanodes based on such heterojunction arrays have shown significantly enhanced photoelectrochemical (PEC) water splitting performance, clearly arising from the above-mentioned efforts. Furthermore, by decorating FeOOH/NiOOH cocatalysts on the heterojunction arrays in tandem, the surface water oxidation kinetics was considerably accelerated, and the resulting Fe-WO3/Fe2WO6/FeOOH/NiOOH photoanode achieved a photocurrent density of 2.78 mA/cm2 at 1.23 V vs reversible hydrogen electrode. This work highlights the benefits of in situ construction of heterojunction arrays for enhancing the PEC performance.
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A cocatalyst is normally deposited on a photoabsorbing semiconductor (PAS) for photoelectrochemical (PEC) water splitting, but with drawbacks of limited loading, reduced light absorption, and tendency of charge recombination. To tackle these problems, a scheme of three-dimensional (3D) decoupling cocatalysts from the PAS with a pore-spanning crisscross conducting polymer host is proposed in this work. To demonstrate the concept, a facile method was developed for the in situ cogrowth of FeO x nanoparticles and conducting polymer (CP) network in various PAS with different microstructures such as a TiO2 nanorod array, WO3 nanosheet array, and planar TiO2 nanoparticle film, generating the bespoke photoanodes. The as-synthesized photoanodes exhibited a significantly enhanced PEC water splitting performance, which is clearly shown to arise from the improved light utilization, increased catalytic active sites, enhanced charge separation, and decreased electrochemical impedance of the photoelectrode. This 3D decoupling strategy is expected to open a promising direction for designing efficient PEC cells.
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Despite the many attempts to build ultrathin 2D-2D heterojunctions via wet chemical methods, the resulting composite materials reported to date suffer from poor interfacial bonding and/or complexity of the synthetic protocols. Encouraged by the structural compatibility of Bi2WO6 and Bi2O2S, both of which are 2D semiconductors sharing a rather similar structural unit of a [Bi2O2]2+ slice in their crystal structures, we have successfully fabricated an ultrathin nanosheet with a tightly bonded 2D-2D heterojunction between the two components by facilely joining the [Bi2O2]2+ and [S]2- slices using a simple two-step hydrothermal method. Such a Bi2WO6-Bi2O2S 2D-2D heterojunction has a five-alternating-layer (Bi2O2S-Bi2WO6-Bi2O2S-Bi2WO6-Bi2O2S) sandwich structure and a thickness down to ca. 5 nm and was obtained by simply growing the Bi2O2S layer in situ on the surface of monolayer Bi2WO6 nanosheets. The judicious combination of Bi2WO6 and Bi2O2S through a 2D-2D heterojunction not only extended light absorption in the visible range but also significantly enhanced photo(electro)chemical water splitting efficiencies in comparison to the bare Bi2WO6 nanosheets alone due to the close-bonding-promoted interfacial charge separation. Our findings provide a viable methodology to build a host of nanomaterials with closely bonded 2D nanosheets, which can be used as photocatalysts and electrocatalysts, among others.
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Purpose: Inhaled corticosteroids, including budesonide (BUD), are widely employed for the treatment of asthma. However, the frequent use of corticosteroids is associated with numerous adverse effects and poses challenges to ongoing drug therapy and patient adherence. Budesonide liposomal nanoparticles (BUD-LNPs) were developed to improve the bioavailability of the drug and thereby improve the effectiveness of asthma treatment. Methods: BUD-LNPs were prepared via thin-film hydration, and the characterizations, stability, and in vitro release of BUD-LNPs were studied. In vitro cellular uptake was observed by laser-scanning confocal microscope (LSCM) and flow cytometry. And the in vitro anti-inflammatory activity of BUD-LNPs was evaluated by measuring the expression of pro-inflammatory cytokines in activated macrophages. Besides, the accumulation time in the lung of drugs delivered via liposomal carriers and free drugs was compared in vivo. And the in vivo therapeutic efficacy of BUD-LNPs was assessed in OVA-induced asthmatic mice. Finally, in vivo biosafety assessment was performed. Results: The particle size, PDI, and zeta potential of BUD-LNPs were 127.63±1.33 nm, 0.27±0.02, and 3.33±0.13 mV, respectively. BUD-LNPs exhibited excellent biosafety and anti-inflammatory activity in vitro. Furthermore, compared with the free drugs, the utilization of liposomal nano-vehicles for drugs delivery could effectively extend the duration of drugs accumulation in the pulmonary system. Additionally, treatment with BUD-LNPs alleviated airway hyperresponsiveness, reduced airway mucus secretion, and mitigated pulmonary inflammation in OVA-induced asthmatic mice. And the BUD-LNPs demonstrated superior therapeutic efficacy compared to free BUD. Conclusion: BUD-LNPs was successfully prepared with excellent stability and sustained release for 24 h in vitro. The data of anti-inflammatory activity, asthma therapeutic effects and safety studies indicated that drug delivery mediated by liposomal nano-vehicles was a feasible and desirable strategy for medical strategy and showed great promise in the clinical therapy of asthma.
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Asma , Budesonida , Ratones , Humanos , Animales , Budesonida/farmacología , Ovalbúmina/farmacología , Asma/inducido químicamente , Asma/tratamiento farmacológico , Pulmón , Antiinflamatorios/farmacología , Corticoesteroides/metabolismo , Corticoesteroides/farmacología , Corticoesteroides/uso terapéutico , Liposomas/farmacologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Qing-Wei-Zhi-Tong Micro-pills (QWZT) is herbal compound used in the treatment of GU, whose functions include clearing the stomach and fire, softening the liver and relieving pain. However, its mechanistic profile on host intestinal microbiota and metabolism has not been determined. AIM OF THE STUDY: The present study aimed to observe the healing effect of QWZT on acetic acid-induced gastric ulcer in a rat model and to preliminarily elucidate its possible therapeutic mechanism from the perspective of host intestinal microbiota and metabolism. MATERIALS AND METHODS: The Wistar male rats (7 weeks old; weight 180-200 g) were randomly divided into normal control group (NC), acetic acid-induced gastric ulcer group (GU), and QWZT treatment group (High dose: 1250 mg/kg/day, Middle dose: 625 mg/kg/day, Low dose: 312.5 mg/kg/day) of 6 rats each. An acetic acid-induced gastric ulcer rat model was constructed based on anatomical surgery. QWZT (High dose, Middle dose, and Low dose) was used to treat gastric ulcer rats for 7 days by gavage. At the end of treatment, the body weight, macroscopic condition of gastric tissue ulcers, pathological changes (HE staining), inflammatory factors, oxidative stress factors, and endocrine factors were assessed in each group of rats. Fresh feces and serum from each group of rats were collected for microbiome and metabolome analysis on the machine, respectively. Drug-disease common targets and functional pathways were captured based on network pharmacology. The complex network of Herbs-Targets-Pathways-Metabolites-Microbiota interactions was constructed. Ultimately, Fecal Microbiota Transplantation (FMT) evaluated the contribution of gut microbiota in disease. RESULTS: QWZT increased the abundance of beneficial bacteria (Bacteroides, Alloprevotella, Rikenellaceae_RC9_gut_group, Lactobacillus, Lachnospiraceae_NK4A136_group, Parabacteroides, etc.), reduced the abundance of harmful bacteria (Micromonospora, Geobacter, Nocardioides, and Arenimonas, etc.), reduced the levels of inflammatory mediators (12,13-EpOME, 9,10-Epoxyoctadecenoic acid, SM(d18:1/16:0) and Leukotriene A4, etc.), restored host metabolic disorders (Linoleic acid metabolism, Glycerophospholipid metabolism, and Arachidonic acid metabolism), and regulated the level of cytokines (IL-6, TNF-a, SOD, MDA, PEG-2 and NO), ultimately exerting an anti-ulcer effect. Apart from that, FMT improved acetic acid-induced gastric ulcers in rats. CONCLUSION: QWZT improved acetic acid-induced gastric ulcers in rats by remodeling intestinal microbiota and regulating host metabolism. This work may promote the process of developing and utilizing clinical applications of QWZT.
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Microbioma Gastrointestinal , Úlcera Gástrica , Masculino , Ratas , Animales , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Ratas Wistar , Metaboloma , Ácido AcéticoRESUMEN
Toxoplasma gondii, a widespread obligate intracellular parasite, can infect almost all warm-blooded animals, including humans. The cellular barrier of the central nervous system (CNS) is generally able to protect the brain parenchyma from infectious damage. However, T. gondii typically causes latent brain infections in humans and other vertebrates. Here, we discuss how T. gondii rhoptry proteins (ROPs) affect signaling pathways in host cells and speculate how this might affect the outcome of Toxoplasma encephalitis.
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Four novel corrosion inhibitors (1, 2, 3 and 4) integrating different tetraphenylethylene (TPE) cations and thiocyanate (SCN-) anions were developed. Weight-loss and electrochemical measurements were employed to assess their protective properties toward carbon steel in 0.5 M H2SO4, revealing them as effective corrosion inhibitors in the order of 3 > 4 > 2 > 1, with the inhibition efficiencies of 2, 3 and 4 all exceeding 97%. The inhibitory effect could be attributed to hard and soft acids and bases theory and the synergistic effect of the charged ingredients. The efficiency trend of the corrosion inhibition, as well as inhibition mechanism, was verified by multi-scaled theoretical simulations combined with grand canonical Monte Carlo and molecular dynamic methods.
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N6-methyladenosine (m6A) is the most abundant internal modification on mammalian messenger RNA. It is installed by a writer complex and can be reversed by erasers such as the fat mass and obesity-associated protein FTO. Despite extensive research, the primary physiological substrates of FTO in mammalian tissues and development remain elusive. Here, we show that FTO mediates m6A demethylation of long-interspersed element-1 (LINE1) RNA in mouse embryonic stem cells (mESCs), regulating LINE1 RNA abundance and the local chromatin state, which in turn modulates the transcription of LINE1-containing genes. FTO-mediated LINE1 RNA m6A demethylation also plays regulatory roles in shaping chromatin state and gene expression during mouse oocyte and embryonic development. Our results suggest broad effects of LINE1 RNA m6A demethylation by FTO in mammals.
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Adenosina/análogos & derivados , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato , Cromatina , Regulación del Desarrollo de la Expresión Génica , Elementos de Nucleótido Esparcido Largo , Células Madre Embrionarias de Ratones , Oocitos , ARN Mensajero , Adenosina/metabolismo , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/metabolismo , Animales , Cromatina/metabolismo , Desmetilación , Elementos de Nucleótido Esparcido Largo/genética , Ratones , Células Madre Embrionarias de Ratones/metabolismo , Oocitos/crecimiento & desarrollo , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
We report an anomalous photoinduced reconstructing and dark self-healing process on Bi2O2S nanoplates by monitoring the time profile of open-circuit potential (OCP). When the light was switched on and off on the nanoplates, we observed pronounced and repeatable decrement-recovery cycles of the OCP signal, which are inexplicable by a rapid electron-hole separation-recombination process only as in a conventional semiconductor. It is proposed that upon irradiation, accumulation of photogenerated holes at the electrode surface caused oxidation of the S layers of Bi2O2S nanoplates into certain intermediates, which, when the light was turned off, were then reduced back to the original state by the electron back flow. Raman scattering spectroscopy provided te S-S vibrational signature of the intermediate, evidencing the hole oxidative dimerization of the S2- species and the inverse reductive S-S dissociation process. The photophysics and photochemistry of semiconductor nanoplates reported here may inspire the development of energy devices, switches, and memristors.
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A complete photoelectrochemical (PEC) water splitting system requires a photocathode and a photoanode to host water oxidation and reduction reactions, respectively. It is thus important to search for efficient photoelectrodes capable of full water splitting. Herein, we report on an exploratory study of a new photoelectrode family of Zn xPbO y-ZnPbO3 and Zn2PbO4-similarly synthesized by a simple and economical method and shown to be a promising photocathode (p-type semiconductor) and photoanode (n-type semiconductor), respectively. From PEC measurements, the bare ZnPbO3 photocathode achieved a photocurrent density of -0.94 mA/cm2 at 0 V versus reversible hydrogen electrode (RHE), whereas the pristine Zn2PbO4 photoanode delivered a photocurrent density of 0.51 mA/cm2 at 1.23 V versus RHE. By depositing suitable cocatalysts onto the photoelectrodes established above, we also demonstrated unassisted overall PEC water splitting, a rare case, if any, wherein a single material system is compositionally engineered for either of the photoelectrodes.
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It is still a challenging issue to design earth-abundant electrocatalysts with low cost, high activity and long-term stability for the hydrogen evolution reaction (HER) based on water splitting in alkaline solutions. Here, we report a facile synthetic route for a three-dimensional, porous Ni/Ni3S2 nano-network on carbon cloth for the efficient catalysis of HER. This unique structure exposes a high proportion of Ni/Ni3S2 hetero-interfaces to the electrolyte, creating a synergetic effect between Ni and Ni3S2 that enhances HER. The synergetic effect at the interface was verified by DFT calculation and involves the interface-assisted heterolytic splitting of H2O into OH- and H+ and the subsequent expeditious H2-forming reaction caused by weakened binding between Ni and H induced by the neighboring Ni3S2. The resulting porous network shows high HER activity in alkaline media, reaching 10 mA cm-2 at 95 mV with a Tafel slope of 66 mV dec-1. This value is much smaller than that of nickel metal, which is currently used in industry.
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Rechargeable Zn-air battery is an ideal type of energy storage device due to its high energy and power density, high safety, and economic viability. Its large-scale application rests upon the availability of active, durable, low-cost electrocatalysts for the oxygen reduction reaction (ORR) in the discharge process and oxygen evolution reaction (OER) in the charge process. Herein we developed a novel ORR/OER bifunctional electrocatalyst for rechargeable Zn-air batteries based on the codoping and hybridization strategies. The B/N-codoped mesoporous nanocarbon supported Co(II)1-xCo(0)x/3Mn(III)2x/3S nanoparticles exhibit a superior OER performance compared to that of IrO2 catalyst and comparable Zn-air battery performance to that of the Pt-based battery. The rechargeable Zn-air battery shows high discharge peak power density (over 250 mW cm(-2)) and current density (180 mA cm(-2) at 1 V), specific capacity (â¼550 mAh g(-1)), small charge-discharge voltage gap of â¼0.72 V at 20 mA cm(-2) and even higher stability than the Pt-based battery. The advanced performance of the bifunctional catalysts highlights the beneficial role of the simultaneous formation of Mn(III) and Co(0) as well as the dispersed hybridization with the codoped nanocarbon support.