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1.
Cell ; 157(6): 1339-1352, 2014 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-24906151

RESUMO

Adipose tissue hypoxia and inflammation have been causally implicated in obesity-induced insulin resistance. Here, we report that, early in the course of high-fat diet (HFD) feeding and obesity, adipocyte respiration becomes uncoupled, leading to increased oxygen consumption and a state of relative adipocyte hypoxia. These events are sufficient to trigger HIF-1α induction, setting off the chronic adipose tissue inflammatory response characteristic of obesity. At the molecular level, these events involve saturated fatty acid stimulation of the adenine nucleotide translocase 2 (ANT2), an inner mitochondrial membrane protein, which leads to the uncoupled respiratory state. Genetic or pharmacologic inhibition of either ANT2 or HIF-1α can prevent or reverse these pathophysiologic events, restoring a state of insulin sensitivity and glucose tolerance. These results reveal the sequential series of events in obesity-induced inflammation and insulin resistance.


Assuntos
Adipócitos/metabolismo , Dieta Hiperlipídica , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Resistência à Insulina , Obesidade/metabolismo , Oxigênio/metabolismo , Translocador 2 do Nucleotídeo Adenina/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Hipóxia Celular , Ácidos Graxos/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Inflamação/metabolismo , Ácido Láctico/metabolismo , Camundongos , Camundongos Knockout , Óxido Nítrico/metabolismo
2.
Cell ; 147(4): 815-26, 2011 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-22078880

RESUMO

Insulin resistance, tissue inflammation, and adipose tissue dysfunction are features of obesity and Type 2 diabetes. We generated adipocyte-specific Nuclear Receptor Corepressor (NCoR) knockout (AKO) mice to investigate the function of NCoR in adipocyte biology, glucose and insulin homeostasis. Despite increased obesity, glucose tolerance was improved in AKO mice, and clamp studies demonstrated enhanced insulin sensitivity in liver, muscle, and fat. Adipose tissue macrophage infiltration and inflammation were also decreased. PPARγ response genes were upregulated in adipose tissue from AKO mice and CDK5-mediated PPARγ ser-273 phosphorylation was reduced, creating a constitutively active PPARγ state. This identifies NCoR as an adaptor protein that enhances the ability of CDK5 to associate with and phosphorylate PPARγ. The dominant function of adipocyte NCoR is to transrepress PPARγ and promote PPARγ ser-273 phosphorylation, such that NCoR deletion leads to adipogenesis, reduced inflammation, and enhanced systemic insulin sensitivity, phenocopying the TZD-treated state.


Assuntos
Adipócitos/metabolismo , Proteínas Correpressoras/genética , Diabetes Mellitus Tipo 2/metabolismo , Resistência à Insulina , Correpressor 1 de Receptor Nuclear/metabolismo , PPAR gama/metabolismo , Animais , Diabetes Mellitus Tipo 2/patologia , Dieta Hiperlipídica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , PPAR gama/antagonistas & inibidores , Fosforilação , Tiazolidinedionas
3.
J Neurosci ; 44(21)2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38565292

RESUMO

Glucagon-like peptide-1 (GLP-1) and its analogs are widely used for diabetes treatment. The paraventricular nucleus (PVN) is crucial for regulating cardiovascular activity. This study aims to determine the roles of GLP-1 and its receptors (GLP-1R) in the PVN in regulating sympathetic outflow and blood pressure. Experiments were carried out in male normotensive rats and spontaneously hypertensive rats (SHR). Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded. GLP-1 and GLP-1R expressions were present in the PVN. PVN microinjection of GLP-1R agonist recombinant human GLP-1 (rhGLP-1) or EX-4 increased RSNA and MAP, which were prevented by GLP-1R antagonist exendin 9-39 (EX9-39) or GLP-1R antagonist 1, superoxide scavenger tempol, antioxidant N-acetylcysteine, NADPH oxidase (NOX) inhibitor apocynin, adenylyl cyclase (AC) inhibitor SQ22536 or protein kinase A (PKA) inhibitor H89. PVN microinjection of rhGLP-1 increased superoxide production, NADPH oxidase activity, cAMP level, AC, and PKA activity, which were prevented by SQ22536 or H89. GLP-1 and GLP-1R were upregulated in the PVN of SHR. PVN microinjection of GLP-1 agonist increased RSNA and MAP in both WKY and SHR, but GLP-1 antagonists caused greater effects in reducing RSNA and MAP in SHR than in WKY. The increased superoxide production and NADPH oxidase activity in the PVN of SHR were augmented by GLP-1R agonists but attenuated by GLP-1R antagonists. These results indicate that activation of GLP-1R in the PVN increased sympathetic outflow and blood pressure via cAMP-PKA-mediated NADPH oxidase activation and subsequent superoxide production. GLP-1 and GLP-1R upregulation in the PVN partially contributes to sympathetic overactivity and hypertension.


Assuntos
Peptídeo 1 Semelhante ao Glucagon , Receptor do Peptídeo Semelhante ao Glucagon 1 , Hipertensão , Núcleo Hipotalâmico Paraventricular , Ratos Endogâmicos SHR , Sistema Nervoso Simpático , Animais , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/metabolismo , Masculino , Hipertensão/fisiopatologia , Hipertensão/metabolismo , Ratos , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/fisiologia , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/antagonistas & inibidores , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Ratos Endogâmicos WKY , Ratos Sprague-Dawley
4.
PLoS Pathog ; 19(7): e1011491, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37399210

RESUMO

Coxiella burnetii is a Gram-negative intracellular pathogen that causes the debilitating disease Q fever, which affects both animals and humans. The only available human vaccine, Q-Vax, is effective but has a high risk of severe adverse reactions, limiting its use as a countermeasure to contain outbreaks. Therefore, it is essential to identify new drug targets to treat this infection. Macrophage infectivity potentiator (Mip) proteins catalyse the folding of proline-containing proteins through their peptidyl prolyl cis-trans isomerase (PPIase) activity and have been shown to play an important role in the virulence of several pathogenic bacteria. To date the role of the Mip protein in C. burnetii pathogenesis has not been investigated. This study demonstrates that CbMip is likely to be an essential protein in C. burnetii. The pipecolic acid derived compounds, SF235 and AN296, which have shown utility in targeting other Mip proteins from pathogenic bacteria, demonstrate inhibitory activities against CbMip. These compounds were found to significantly inhibit intracellular replication of C. burnetii in both HeLa and THP-1 cells. Furthermore, SF235 and AN296 were also found to exhibit antibiotic properties against both the virulent (Phase I) and avirulent (Phase II) forms of C. burnetii Nine Mile Strain in axenic culture. Comparative proteomics, in the presence of AN296, revealed alterations in stress responses with H2O2 sensitivity assays validating that Mip inhibition increases the sensitivity of C. burnetii to oxidative stress. In addition, SF235 and AN296 were effective in vivo and significantly improved the survival of Galleria mellonella infected with C. burnetii. These results suggest that unlike in other bacteria, Mip in C. burnetii is required for replication and that the development of more potent inhibitors against CbMip is warranted and offer potential as novel therapeutics against this pathogen.


Assuntos
Coxiella burnetii , Febre Q , Animais , Humanos , Peptidilprolil Isomerase/metabolismo , Proteínas de Bactérias/metabolismo , Peróxido de Hidrogênio/metabolismo , Bactérias/metabolismo , Macrófagos/metabolismo
5.
J Mol Cell Cardiol ; 195: 24-35, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39002608

RESUMO

Pulmonary hypertension (PH) is characterized by excessive proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs), in which inflammatory signaling caused by activation of the NF-κB pathway plays an important role. A20 is an important negative regulator of the NF-κB pathway, and zinc promotes the expression of A20 and exerts a protective effect against various diseases (e.g. COVID19) by inhibiting the inflammatory signaling. The role of A20 and intracellular zinc signaling in PH has been explored, but the extracellular zinc signaling is not well understood, and whether zinc has protective effects on PH is still elusive. Using inductively coupled plasma mass spectrometry (ICP-MS), we studied the alteration of trace elements during the progression of monocrotaline (MCT)-induced PH and found that serum zinc concentration was decreased with the onset of PH accompanied by abnormalities of other three elements, including copper, chromium, and magnesium. Zinc chloride injection with the dosage of 5 mg/kg intraperitoneally partially corrected this abnormality and inhibited the progression of PH. Zinc supplementation induced the expression of A20 in lung tissue and reduce the inflammatory responses. In vitro, zinc supplementation time-dependently upregulated the expression of A20 in PASMCs, therefore correcting the excessive proliferation and migration of cells caused by hypoxia. Using genetically encoded-FRET based zinc probe, we found that these effects of zinc ions are not achieved by entering cells, but most likely by activating cell surface zinc receptor (ZnR/GPR39). These results provide the first evidence of the effectiveness of zinc supplementation in the treatment of PH.


Assuntos
Hipertensão Pulmonar , Monocrotalina , Miócitos de Músculo Liso , Proteína 3 Induzida por Fator de Necrose Tumoral alfa , Regulação para Cima , Zinco , Animais , Monocrotalina/toxicidade , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/tratamento farmacológico , Zinco/metabolismo , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/metabolismo , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/genética , Ratos , Masculino , Regulação para Cima/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ratos Sprague-Dawley , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Artéria Pulmonar/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , Pulmão/efeitos dos fármacos
6.
J Proteome Res ; 23(5): 1713-1724, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38648079

RESUMO

Non-small-cell lung cancer (NSCLC), a common malignant tumor, requires deeper pathogenesis investigation. Autophagy is an evolutionarily conserved lysosomal degradation process that is frequently blocked during cancer progression. It is an urgent need to determine the novel autophagy-associated regulators in NSCLC. Here, we found that pirin was upregulated in NSCLC, and its expression was positively correlated with poor prognosis. Overexpression of pirin inhibited autophagy and promoted NSCLC proliferation. We then performed data-independent acquisition-based quantitative proteomics to identify the differentially expressed proteins (DEPs) in pirin-overexpression (OE) or pirin-knockdown (KD) cells. Among the pirin-regulated DEPs, ornithine decarboxylase 1 (ODC1) was downregulated in pirin-KD cells while upregulated along with pirin overexpression. ODC1 depletion reversed the pirin-induced autophagy inhibition and pro-proliferation effect in A549 and H460 cells. Immunohistochemistry showed that ODC1 was highly expressed in NSCLC cancer tissues and positively related with pirin. Notably, NSCLC patients with pirinhigh/ODC1high had a higher risk in terms of overall survival. In summary, we identified pirin and ODC1 as a novel cluster of prognostic biomarkers for NSCLC and highlighted the potential oncogenic role of the pirin/ODC1/autophagy axis in this cancer type. Targeting this pathway represents a possible therapeutic approach to treat NSCLC.


Assuntos
Autofagia , Carcinoma Pulmonar de Células não Pequenas , Proliferação de Células , Progressão da Doença , Neoplasias Pulmonares , Ornitina Descarboxilase , Feminino , Humanos , Masculino , Células A549 , Autofagia/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Ornitina Descarboxilase/metabolismo , Ornitina Descarboxilase/genética , Prognóstico , Regulação para Cima
7.
Am J Physiol Renal Physiol ; 327(5): F885-F898, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39298550

RESUMO

Renal denervation (RDN) has been used for treating resistant hypertension. A few recent studies have shown vagal innervation of kidneys causing confusion. This study aimed to provide anatomical and functional evidence for renal autonomic innervation. Experiments were performed in male Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Pseudorabies virus (PRV) in the paraventricular nucleus and rostral ventrolateral medulla was prevented by bilateral RDN, but not subdiaphragmatic vagotomy. PRV did not appear in the dorsal motor nucleus of the vagus and nucleus tractus solitarii 72 h after renal injection of PRV. Adrenergic fibers were approximately seven times more than cholinergic fibers in the main renal artery (MRA) and its first (1RA) and second grade (2RA) branches. Adrenergic fibers in 1RA were more than those in MRA and 2RA. Tyrosine hydroxylase immunoreactivity in these arteries was higher in SHR than in WKY. Norepinephrine (NE) increased and α-receptor antagonist reduced vascular ring tension of renal arteries. The effect of NE was greater in 1RA and 2RA than in MRA, which was prevented by α-receptor antagonist. Acetylcholine (ACh) or blockage of ß-receptors, M receptors, or N receptors had no significant effects on vascular ring tension and the effect of NE. Renal blood flow was reduced by electrical stimulation of renal nerves but not affected by stimulation of the subdiaphragmatic vagus. These results provide anatomical and functional evidence that kidneys are innervated and renal blood flow is regulated by renal sympathetic nerves rather than the vagus. Renal vasoconstriction is regulated by NE and adrenergic fibers rather than ACh or cholinergic fibers in WKY and SHR.NEW & NOTEWORTHY Kidneys are innervated by renal nerves rather than the vagus. Adrenergic fibers in renal arteries are about seven times more than cholinergic fibers. Renal vasoconstriction is regulated by norepinephrine and adrenergic fibers rather than acetylcholine or cholinergic fibers. Renal blood flow is regulated by renal sympathetic nerves and is not affected by the vagus. These findings provide anatomical and functional evidence for renal autonomic innervation in normotensive and hypertensive rats.


Assuntos
Hipertensão , Rim , Norepinefrina , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Artéria Renal , Animais , Masculino , Rim/inervação , Rim/irrigação sanguínea , Hipertensão/fisiopatologia , Hipertensão/metabolismo , Artéria Renal/inervação , Norepinefrina/metabolismo , Vasoconstrição , Ratos , Sistema Nervoso Autônomo/metabolismo , Sistema Nervoso Autônomo/fisiopatologia , Pressão Sanguínea , Fibras Adrenérgicas/metabolismo , Modelos Animais de Doenças , Herpesvirus Suídeo 1 , Nervo Vago/cirurgia , Fibras Colinérgicas/metabolismo
8.
Eur J Neurosci ; 60(5): 4830-4842, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39044301

RESUMO

Chemerin is an adipokine that contributes to metabolism regulation. Nucleus tractus solitarius (NTS) is the first relay station in the brain for accepting various visceral afferent activities for regulating cardiovascular activity. However, the roles of chemerin in the NTS in regulating sympathetic activity and blood pressure are almost unknown. This study aimed to determine the role and potential mechanism of chemerin in the NTS in modulating sympathetic outflow and blood pressure. Bilateral NTS microinjections were performed in anaesthetized adult male Sprague-Dawley rats. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) were continuously recorded. Chemerin and its receptor chemokine-like receptor 1 (CMKLR1) were highly expressed in caudal NTS (cNTS). Microinjection of chemerin-9 to the cNTS increased RSNA, MAP and HR, which were prevented by CMKLR1 antagonist α-NETA, superoxide scavenger tempol or N-acetyl cysteine, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors diphenyleneiodonium or apocynin. Chemerin-9 increased superoxide production and NADPH oxidase activity in the cNTS. The increased superoxide production induced by chemerin-9 was inhibited by α-NETA. The effects of cNTS microinjection of chemerin-9 on the RSNA, MAP and HR were attenuated by the pretreatment with paraventricular nucleus (PVN) microinjection of NMDA receptor antagonist MK-801 rather than AMPA/kainate receptor antagonist CNQX. These results indicate that chemerin-9 in the NTS increases sympathetic outflow, blood pressure and HR via CMKLR1-mediated NADPH oxidase activation and subsequent superoxide production in anaesthetized normotensive rats. Glutamatergic inputs in the PVN are needed for the chemerin-9-induced responses.


Assuntos
Pressão Sanguínea , Quimiocinas , Ratos Sprague-Dawley , Núcleo Solitário , Sistema Nervoso Simpático , Animais , Núcleo Solitário/efeitos dos fármacos , Núcleo Solitário/fisiologia , Núcleo Solitário/metabolismo , Masculino , Quimiocinas/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Sistema Nervoso Simpático/fisiologia , Sistema Nervoso Simpático/efeitos dos fármacos , Ratos , Receptores de Quimiocinas/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/administração & dosagem , NADPH Oxidases/metabolismo , Superóxidos/metabolismo
9.
Small ; 20(2): e2305321, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37658493

RESUMO

2D MXene-Ti3 C2 Tx holds great promise in various electronic applications, especially for electromagnetic interference (EMI) shielding devices and supercapacitors. Ti3 C2 Tx synthesis typically involves the use of hazardous fluorine-containing chemicals that can result in the formation of inert fluoride functional groups on the surface of Ti3 C2 Tx , severely degrading its properties and posing a threat to the performance of electron transfer among electrical devices. Herein, a supercritical carbon dioxide-based ternary solution (scCO2 /DMSO/HCl) to produce fluoride-free Ti3 C2 Tx in mild conditions (via 0.5 m HCl, 20 MPa, 32 °C) is reported. The fluorine-free Ti3 C2 Tx films electrode presents an excellent gravimetric capacitance of 320 F g-1 at 2 mV s-1 in 1 m H2 SO4 . Besides, it is demonstrated that fluorine-free Ti3 C2 Tx films exhibit outstanding EMI shielding efficiency of 53.12 dB at 2.5 µm thickness. The findings offer a mild and practical approach to producing fluoride-free Ti3 C2 Tx and open opportunities for exploring MXenes' potential applications in various fields.

10.
Mol Pharm ; 21(11): 5864-5879, 2024 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-39378327

RESUMO

Despite the advancements in cancer therapy, delivering active pharmaceutical ingredients (APIs) using nanoparticles remains challenging due to the failed conveyance of the required drug payload, poor targeting ability, and poor biodistribution, hampering their clinical translation. Recently, the appropriate design of materials with intrinsic therapeutic functionalities has garnered enormous interest in the development of various intelligent therapeutic nanoplatforms. In this study, we demonstrate the fabrication of transition metal (molybdenum, Mo)-doped manganese dioxide (MnO2) nanoarchitectures, exhibiting diagnostic (magnetic resonance imaging, MRI) and therapeutic (chemodynamic therapy, CDT) functionalities. The facile hydrothermal approach-assisted Mo-doped MnO2 flower-like nanostructures offered tailorable morphologies in altered dimensions, precise therapeutic effects, exceptional biocompatibility, and biodegradability in the tumor microenvironment. The resultant defects due to doped Mo species exhibited peroxidase and oxidase activities, improving glutathione (GSH) oxidation. The two sets of variable valence metal ion pairs (Mn2+/Mn4+ and Mo5+/Mo6+) and their interplay could substantially improve the Fenton-like reaction and generate toxic hydroxyl radicals (•OH), thus achieving CDT-assisted antitumor effects. As inherent T1-MRI agents, these MnO2 nanoparticles displayed excellent MRI efficacy in vitro. Together, we believe that these conformational Mo-doped MnO2 nanoarchitectures with two pairs of variable valence states could potentiate drugless therapy in pharmaceutics.


Assuntos
Imageamento por Ressonância Magnética , Compostos de Manganês , Molibdênio , Óxidos , Nanomedicina Teranóstica , Molibdênio/química , Óxidos/química , Compostos de Manganês/química , Humanos , Nanomedicina Teranóstica/métodos , Camundongos , Animais , Imageamento por Ressonância Magnética/métodos , Linhagem Celular Tumoral , Neoplasias/tratamento farmacológico , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Nanopartículas/química , Manganês/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem , Microambiente Tumoral/efeitos dos fármacos , Nanoestruturas/química , Distribuição Tecidual
11.
Langmuir ; 40(26): 13550-13561, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38902967

RESUMO

There has been a growing emphasis on facile preparation of binary heterogeneous composite materials. Leveraging the eco-friendly efficiency of supercritical CO2 technology, we achieved precise control over the influencing factors of mass transfer, enabling the accurate modulation of the resulting product morphology and properties. In the current study, CuxO/ZrOy composite materials were prepared using this technology and calcined to obtain electrode materials for the detection of cysteine (Cys). Essential comprehensive characterization techniques were employed to elucidate the heterojunction. The resulting electrode demonstrated a linear response to Cys within a concentration range of 0.5 nM to 1 µM, featuring a high sensitivity of 1035 µA·cm-2·µM-1 and a low detection limit of 97.3 nM. Thus, establishing a novel avenue for nonenzyme-based electrochemical sensors tailored for biologically active Cys detection through the implementation of a heterogeneous structure.

12.
Eur J Clin Microbiol Infect Dis ; 43(5): 1031-1036, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38472521

RESUMO

PURPOSE: We aimed to show the increasing incidence of invasive fungal infections due to Volvariella Volvacea in patients with immunosuppression. METHODS: We present a case of an invasive fungal infection caused by Volvariella volvacea, and summarize the clinical and pathological features based on this case and a review of the literature. RESULTS: A total of seven patients with IFIs due to Volvariella Volvacea have been reported in the literature. The majority of cases have been obtained between 2019 and 2022. Including our case, they all had acquired immunosuppression. The lung and brain were the most commonly affected organs. All eight of these patients received antifungal therapy, but five still died one to seven months after occurrences of IFIs. CONCLUSION: The incidence of invasive fungal infections due to Volvariella Volvacea is increasing in recent years. It mainly occurred in patients with immunosuppression, especially in patients with malignant hematological cancers, and increased mortality.


Assuntos
Antifúngicos , Infecções Fúngicas Invasivas , Volvariella , Humanos , Volvariella/genética , Infecções Fúngicas Invasivas/epidemiologia , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/microbiologia , Infecções Fúngicas Invasivas/mortalidade , Incidência , Masculino , Antifúngicos/uso terapêutico , Hospedeiro Imunocomprometido , Pessoa de Meia-Idade , Feminino , Idoso
13.
Mol Biol Rep ; 51(1): 80, 2024 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-38183537

RESUMO

BACKGROUND: Continuous exposure to UVB is the main extrinsic cause of skin photodamage, which is associated with oxidative stress, DNA damage, apoptosis and degradation of collagen. Rapamycin, a mechanistic target inhibitor of rapamycin complex 1 (mTORC1), has been shown to play a crucial role anti-tumor and aging retardation, but its mechanism of action in UVB-induced photodamage still remains unknown. In this study, we investigated the role of rapamycin and Hspb2 (also known as Hsp27) in UVB-induced photodamage in mice. METHODS AND RESULTS: We constructed skin acute photodamage models on the ears of WT and Hspb2 KO mice, respectively, and administered rapamycin treatment. Histological results showed that knockout of the hspb2 exacerbated the skin damage, as evidenced by thickening of the epidermis, breakage and disruption of collagen fibers and reduction in their number, which is reversed by rapamycin treatment. In addition, hspb2 knockout promoted UVB-induced apoptosis and reduced autophagy levels, with a significant increase in p53 levels and Bax/Bcl-2 ratio, a reduction in LC3II/I ratio and an increase in p62 levels in the KO mice compared to those in WT mice after the same dose of UVB irradiation. Rapamycin was also found to inhibit collagen degradation induced by hspb2 knockdown through activation of the TGF-ß/Smad signaling pathway. CONCLUSIONS: Rapamycin can alleviate skin photodamage from Hspb2 knockout to some extent. It may be a potential therapeutic drug for skin photodamage. In this study, we investigated the role of rapamycin and Hspb2 in UVB-induced photodamage in mice. Histological results showed that knockout of the hspb2 exacerbated the skin damage, as evidenced by thickening of the epidermis, breakage and disruption of collagen fibers and reduction in their number, which is reversed by rapamycin treatment. In addition, hspb2 knockout promoted UVB-induced apoptosis and reduced autophagy levels. Rapamycin was also found to inhibit collagen degradation induced by hspb2 knockdown through activation of the TGF-ß/Smad signaling pathway. We conclude that rapamycin and Hspb2 exert a synergistic protective effect in skin photodamage.


Assuntos
Apoptose , Epiderme , Animais , Camundongos , Autofagia , Alvo Mecanístico do Complexo 1 de Rapamicina , Colágeno , Fator de Crescimento Transformador beta , Proteínas de Choque Térmico HSP27/genética
14.
Environ Res ; 258: 119460, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38906451

RESUMO

To investigate the inhibitory effects of various transition metal ions on nitrogen removal and their underlying mechanisms, the single and combined effects of Cu2+ Ni2+ and Zn2+ on Heterotrophic nitrification-aerobic denitrification (HN-AD) bacteria Acinetobacter sp. TAC-1 were studied in a batch experiment system. The results revealed that increasing concentrations of Cu2+ and Ni2+ had a detrimental effect on the removal of ammonium nitrogen (NH4+-N) and total nitrogen (TN). Specifically, Cu2+ concentration of 10 mg/L, the TN degradation rate was 55.09%, compared to 77.60% in the control group. Cu2+ exhibited a pronounced inhibitory effect. In contrast, Zn2+ showed no apparent inhibitory effect on NH4+-N removal and even enhanced TN removal at lower concentrations. However, when the mixed ion concentration of Zn2++Ni2+ exceeded 5 mg/L, the removal rates of NH4+-N and TN were significantly reduced. Moreover, transition metal ions did not significantly impact the removal rates of chemical oxygen demand (COD). The inhibition model fitting results indicated that the inhibition sequence was Cu2+ > Zn2+ > Ni2+. Transcriptome analysis demonstrated that metal ions influence TAC-1 activity by modulating the expression of pivotal genes, including zinc ABC transporter substrate binding protein (znuA), ribosomal protein (rpsM), and chromosome replication initiation protein (dnaA) and DNA replication of TAC-1 under metal ion stress, leading to disruptions in transcription, translation, and cell membrane structure. Finally, a conceptual model was proposed by us to summarize the inhibition mechanism and possible response strategies of TAC-1 bacteria under metal ion stress, and to address the lack of understanding regarding the influence mechanism of TAC-1 on nitrogen removal in wastewater co-polluted by metal and ammonia nitrogen. The results provided practical guidance for the management of transition metal and ammonia nitrogen co-polluted water bodies, as well as the removal of high nitrogen.


Assuntos
Desnitrificação , Nitrificação , Acinetobacter/metabolismo , Acinetobacter/genética , Processos Heterotróficos , Aerobiose , Elementos de Transição/metabolismo , Nitrogênio/metabolismo , Poluentes Químicos da Água/metabolismo
15.
J Chem Phys ; 161(13)2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39356062

RESUMO

The electric dipole polarizabilities and the tune-out wavelengths for the n3S1 (n = 2, 3) states of Be2+ are determined through the application of the relativistic full-configuration-interaction approach. Our calculations directly integrate the mass shift operator into the Dirac-Coulomb-Breit Hamiltonian and further assess the quantum electrodynamics (QED) correction to the dynamic dipole polarizabilities using perturbation theory. The results reveal that the static electric dipole polarizability of the 23S1 and 33S1 states, as well as the 93 nm tune-out wavelength of the 23S1 state and the 238 nm tune-out wavelength of the 33S1 state, exhibits a high sensitivity to QED correction, which exceeds 80 ppm, providing a sensitive test for atomic structure theory.

16.
Luminescence ; 39(5): e4763, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38761029

RESUMO

The development of optical optics for low-location road lighting is a challenging problem in providing high luminance and uniformity of illumination and meeting many other specific requirements. This study proposes an optical design method of low-location illumination based on an asymmetric double freeform surface lens. The ray emitted from the light source is refracted and reflected through the different surface types to the corresponding area of the receiving surface. In the design example, the road has dual-side mounted luminaires and a width of 6 m, and a height of 0.8 m. Simulation results indicate that, compared with conventional high-pole streetlights, the luminance uniformity had increased from 0.60 to 0.66, the illuminance uniformity had improved from 0.75 to 0.86, and the glare had been reduced.


Assuntos
Iluminação , Propriedades de Superfície , Luz , Desenho de Equipamento
17.
J Clin Ultrasound ; 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39223774

RESUMO

We present a case study highlighting prenatal ultrasound findings in monozygotic twins with chromosome 17q12 deletion syndrome. Fetus A exhibited bilateral fetal pyelectasis and talipes equinovarus, while fetus B showed hyperechogenic kidneys. Despite sharing the same de novo variant, the twins displayed distinct clinical phenotypes, suggesting the presence of non-genetic factors influencing the phenotypic variability of this syndrome. This case represents the first documented instance of prenatally identified identical twins affected by 17q12 deletion syndrome.

18.
Small ; 19(8): e2205315, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36470676

RESUMO

In recent years, the rapid development of modern society is calling for advanced energy storage to meet the growing demands of energy supply and generation. As one of the most promising energy storage systems, secondary batteries are attracting much attention. The electrolyte is an important part of the secondary battery, and its composition is closely related to the electrochemical performance of the secondary batteries. Lithium-ion battery electrolyte is mainly composed of solvents, additives, and lithium salts, which are prepared according to specific proportions under certain conditions and according to the needs of characteristics. This review analyzes the advantages and current problems of the liquid electrolytes in lithium-ion batteries (LIBs) from the mechanism of action and failure mechanism, summarizes the research progress of solvents, lithium salts, and additives, analyzes the future trends and requirements of lithium-ion battery electrolytes, and points out the emerging opportunities in advanced lithium-ion battery electrolytes development.

19.
Small ; 19(34): e2301952, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37086138

RESUMO

Converting ubiquitous ambient low-grade thermal energy into electricity is of great significance for tackling the fossil energy shortage and environmental crisis but poses a considerable challenge. Here, a novel thermal-driven triboelectric nanogenerator (TD-TENG) is developed, which utilizes a bimetallic beam with a bi-stable dynamic feature to induce continuous mechanical oscillations, and the mechanical motion is then converted into electric power using a contact-separation TENG. The thermal process inside the device is systematically investigated and effective thermal management is conducted accordingly. After optimization, the TD-TENG can produce a power density of 323.9 mW m-2 at 59.5 °C, obtaining the highest record of TENG-based thermal energy harvesters. Besides, the first prototype of TENG-based solar thermal harvester is successfully demonstrated, with a power density of 364.4 mW m-2 . Moreover, the TD-TENG can harvest and dissipate the heat at the same time, exhibiting great potential in over-heated electronics protection as well as architectural energy conservation. Most importantly, the operation temperature range of the TD-TENG is tunable by adjusting the bimetal parameters, allowing the device a wide and flexible working thermal gradient. These unique properties validate the TD-TENG is a simple, feasible, cost-effective, and high-efficient low-grade thermal energy harvester.

20.
Small ; 19(52): e2304781, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37635095

RESUMO

Metal oxides with diverse compositions and structures have garnered considerable interest from researchers in various reactions, which benefits from transmission electron microscopy (TEM) in determining their morphologies, phase, structural and chemical information. Recent breakthroughs have made liquid-phase TEM a promising imaging platform for tracking the dynamic structure, morphology, and composition evolution of metal oxides in solution under work conditions. Herein, this review introduces the recent advances in liquid cells, especially closed liquid cell chips. Subsequently, the recent progress including particle growth, phase transformation, self-assembly, core-shell nanostructure growth, and chemical etching are introduced. With the late technical advances in TEM and liquid cells, liquid-phase TEM is used to characterize many fundamental processes of metal oxides for CO2 reduction and water-splitting reactions. Finally, the outlook and challenges in this research field are discussed. It is believed this compilation inspires and stimulates more efforts in developing and utilizing in situ liquid-phase TEM for metal oxides at the atomic scale for different applications.

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