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1.
PLoS Biol ; 21(12): e3002441, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38096144

RESUMO

Siphophages have a long, flexible, and noncontractile tail that connects to the capsid through a neck. The phage tail is essential for host cell recognition and virus-host cell interactions; moreover, it serves as a channel for genome delivery during infection. However, the in situ high-resolution structure of the neck-tail complex of siphophages remains unknown. Here, we present the structure of the siphophage lambda "wild type," the most widely used, laboratory-adapted fiberless mutant. The neck-tail complex comprises a channel formed by stacked 12-fold and hexameric rings and a 3-fold symmetrical tip. The interactions among DNA and a total of 246 tail protein molecules forming the tail and neck have been characterized. Structural comparisons of the tail tips, the most diversified region across the lambda and other long-tailed phages or tail-like machines, suggest that their tail tip contains conserved domains, which facilitate tail assembly, receptor binding, cell adsorption, and DNA retaining/releasing. These domains are distributed in different tail tip proteins in different phages or tail-like machines. The side tail fibers are not required for the phage particle to orient itself vertically to the surface of the host cell during attachment.


Assuntos
Bacteriófagos , Bacteriófagos/genética , Ligação Proteica , Proteínas do Capsídeo/metabolismo , DNA/metabolismo , Proteínas da Cauda Viral/genética , Proteínas da Cauda Viral/química , Proteínas da Cauda Viral/metabolismo
2.
Brief Bioinform ; 24(6)2023 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-37903415

RESUMO

The identification of viruses from negative staining transmission electron microscopy (TEM) images has mainly depended on experienced experts. Recent advances in artificial intelligence have enabled virus recognition using deep learning techniques. However, most of the existing methods only perform virus classification or semantic segmentation, and few studies have addressed the challenge of virus instance segmentation in TEM images. In this paper, we focus on the instance segmentation of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and other respiratory viruses and provide experts with more effective information about viruses. We propose an effective virus instance segmentation network based on the You Only Look At CoefficienTs backbone, which integrates the Swin Transformer, dense connections and the coordinate-spatial attention mechanism, to identify SARS-CoV-2, H1N1 influenza virus, respiratory syncytial virus, Herpes simplex virus-1, Human adenovirus type 5 and Vaccinia virus. We also provide a public TEM virus dataset and conduct extensive comparative experiments. Our method achieves a mean average precision score of 83.8 and F1 score of 0.920, outperforming other state-of-the-art instance segmentation algorithms. The proposed automated method provides virologists with an effective approach for recognizing and identifying SARS-CoV-2 and assisting in the diagnosis of viruses. Our dataset and code are accessible at https://github.com/xiaochiHNU/Virus-Instance-Segmentation-Transformer-Network.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A , Humanos , Inteligência Artificial , Algoritmos , SARS-CoV-2
3.
Proc Natl Acad Sci U S A ; 119(31): e2119439119, 2022 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-35895681

RESUMO

Archaeal viruses with a spindle-shaped virion are abundant and widespread in extremely diverse environments. However, efforts to obtain the high-resolution structure of a spindle-shaped virus have been unsuccessful. Here, we present the structure of SSV19, a spindle-shaped virus infecting the hyperthermophilic archaeon Sulfolobus sp. E11-6. Our near-atomic structure reveals an unusual sevenfold symmetrical virus tail consisting of the tailspike, nozzle, and adaptor proteins. The spindle-shaped capsid shell is formed by seven left-handed helical strands, constructed of the hydrophobic major capsid protein, emanating from the highly glycosylated tail assembly. Sliding between adjacent strands is responsible for the variation of a virion in size. Ultrathin sections of the SSV19-infected cells show that SSV19 virions adsorb to the host cell membrane through the tail after penetrating the S-layer. The tailspike harbors a putative endo-mannanase domain, which shares structural similarity to a Bacteroides thetaiotaomicro endo-mannanase. Molecules of glycerol dibiphytanyl glycerol tetraether lipid were observed in hydrophobic clefts between the tail and the capsid shell. The nozzle protein resembles the stem and clip domains of the portals of herpesviruses and bacteriophages, implying an evolutionary relationship among the archaeal, bacterial, and eukaryotic viruses.


Assuntos
Fuselloviridae , Sulfolobus , Proteínas do Capsídeo/química , Fuselloviridae/química , Fuselloviridae/genética , Fuselloviridae/isolamento & purificação , Genoma Viral , Glicerol , Sulfolobus/virologia , Vírion/química , Vírion/genética , Vírion/isolamento & purificação
4.
Immunol Cell Biol ; 102(4): 256-268, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38361210

RESUMO

We explored the frequency of CD14-CD10-CD45+HLA-DR-SSC++ neutrophils (CD10- neutrophils) in patients with non-Hodgkin's lymphoma (NHL), and their immunologic characteristics and clinical significance. Patients with NHL who were newly diagnosed (NDP; n = 33), in remission (RMP; n = 28) and relapsed (RLP; n = 29) were included, and 47 volunteers were recruited as healthy controls (HCs). The frequency of CD10- neutrophils in the peripheral blood from HC and patients with NHL was detected. CD10- and CD10+ neutrophils were sorted, and their cytology was analyzed. CD3+ T cells were also isolated and cultured with the autologous CD10- or CD10+ neutrophils, after which the proliferation and death rates of T cells were determined. The levels of arginase-1 (Arg-1) and reactive oxygen species (ROS) in CD10+ or CD10- neutrophils were examined. Few CD10- neutrophils were detected in HCs but were significantly elevated in patients with NHL, especially in NDP and RLP. In addition, CD10- neutrophils in NDP with advanced stage and high risk were markedly higher than those in NDP with limited stage and low risk. In RMP and RLP, the relapse-free survival and overall survival in patients with high CD10- neutrophils were shorter than those with low CD10- neutrophils. CD10- neutrophils from patients with NHL, which mainly consist of immature neutrophils, inhibit T-cell proliferation and facilitate T-cell death. Furthermore, a significant increase was observed in Arg-1 expression, along with an increase to a certain extent in ROS. CD10- neutrophils in patients with NHL have characteristics of myeloid-derived suppressor cells and may be related to disease progression and poor prognosis.


Assuntos
Linfoma não Hodgkin , Células Supressoras Mieloides , Humanos , Neutrófilos , Espécies Reativas de Oxigênio , Linfoma não Hodgkin/patologia , Antígenos HLA-DR/metabolismo , Progressão da Doença
5.
Bioconjug Chem ; 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38904455

RESUMO

Currently, clinical therapeutic strategies for nasopharyngeal carcinoma (NPC) confront insurmountable dilemmas in which surgical resection is incomplete and chemotherapy/radiotherapy has significant side effects. Phototherapy offers a maneuverable, effective, and noninvasive pattern for NPC therapy. Herein, we developed a lysosome-targeted and pH-responsive nanophototheranostic for near-infrared II (NIR-II) fluorescence imaging-guided photodynamic therapy (PDT) and photothermal therapy (PTT) of NPC. A lysosome-targeted S-D-A-D-S-type NIR-II phototheranostic molecule (IRFEM) is encapsulated within the acid-sensitive amphiphilic DSPE-Hyd-PEG2k to form IRFEM@DHP nanoparticles (NPs). The prepared IRFEM@DHP exhibits a good accumulation in the acidic lysosomes for facilitating the release of IRFEM, which could disrupt lysosomal function by generating an amount of heat and ROS under laser irradiation. Moreover, the guidelines of NIR-II fluorescence enhance the accuracy of PTT/PDT for NPC and avoid damage to normal tissues. Remarkably, IRFEM@DHP enable efficient antitumor effects both in vitro and in vivo, opening up a new avenue for precise NPC theranostics.

6.
Scand J Immunol ; 99(4): e13352, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-39008028

RESUMO

Chimeric antigen receptor T-cell (CAR-T) therapy has demonstrated remarkable efficacy in treating relapsed/refractory acute B-cell lymphoblastic leukaemia (R/R B-ALL). However, a subset of patients does not benefit from CAR-T therapy. Our study aims to identify predictive indicators and establish a model to evaluate the feasibility of CAR-T therapy. Fifty-five R/R B-ALL patients and 22 healthy donors were enrolled. Peripheral blood lymphocyte subsets were analysed using flow cytometry. Sensitivity, specificity, accuracy, positive and negative predictive values and receiver operating characteristic (ROC) areas under the curve (AUC) were determined to evaluate the predictive values of the indicators. We identified B lymphocyte, regulatory T cell (Treg) and peripheral blood minimal residual leukaemia cells (B-MRD) as indicators for predicting the success of CAR-T cell preparation with AUC 0.936, 0.857 and 0.914. Furthermore, a model based on CD3+ T count, CD4+ T/CD8+ T ratio, Treg and extramedullary diseases (EMD) was used to predict the response to CAR-T therapy with AUC of 0.938. Notably, a model based on CD4+ T/CD8+ T ratio, B, Treg and EMD were used in predicting the success of CAR-T therapy with AUC 0.966 [0.908-1.000], with specificity (92.59%) and sensitivity (91.67%). In the validated group, the predictive model predicted the success of CAR-T therapy with specificity (90.91%) and sensitivity (100%). We have identified several predictive indicators for CAR-T cell therapy success and a model has demonstrated robust predictive capacity for the success of CAR-T therapy. These results show great potential for guiding informed clinical decisions in the field of CAR-T cell therapy.


Assuntos
Imunoterapia Adotiva , Receptores de Antígenos Quiméricos , Humanos , Imunoterapia Adotiva/métodos , Masculino , Feminino , Adulto , Adolescente , Pessoa de Meia-Idade , Receptores de Antígenos Quiméricos/imunologia , Criança , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/imunologia , Adulto Jovem , Pré-Escolar , Resultado do Tratamento , Linfócitos T Reguladores/imunologia , Curva ROC , Recidiva
7.
Cell Commun Signal ; 22(1): 62, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263047

RESUMO

BACKGROUND: Previous research has reported that prenatal exposure to dexamethasone (PDE) results in organ dysplasia and increased disease susceptibility in offspring. This study aimed to investigate the epigenetic mechanism of metabolic syndrome induced by PDE in offspring. METHODS: Pregnant Wistar rats were administered dexamethasone, and their offspring's serum and liver tissues were analyzed. The hepatocyte differentiation model was established to unveil the molecular mechanism. Neonatal cord blood samples were collected to validate the phenomenon and mechanism. RESULTS: The findings demonstrated that PDE leads to insulin resistance and typical metabolic syndrome traits in adult offspring rats, which originated from fetal liver dysplasia. Additionally, PDE reduced serum corticosterone level and inhibited hepatic insulin-like growth factor 1 (IGF1) signaling in fetal rats. It further revealed that liver dysplasia and functional impairment induced by PDE persist after birth, driven by the continuous downregulation of serum corticosterone and hepatic IGF1 signaling. Both in vitro and in vivo experiments confirmed that low endogenous corticosterone reduces the histone 3 lysine 9 acetylation (H3K27ac) level of IGF1 and its expression by blocking glucocorticoid receptor α, special protein 1, and P300 into the nucleus, resulting in hepatocyte differentiation inhibition and liver dysplasia. Intriguingly, neonatal cord blood samples validated the link between reduced liver function in neonates induced by PDE and decreased serum cortisol and IGF1 levels. CONCLUSIONS: This study demonstrated that low endogenous glucocorticoid level under PDE lead to liver dysplasia by downregulating the H3K27ac level of IGF1 and its expression, ultimately contributing to metabolic syndrome in adult offspring.


Assuntos
Síndrome Metabólica , Feminino , Gravidez , Animais , Ratos , Ratos Wistar , Corticosterona , Epigênese Genética , Hiperplasia , Dexametasona
8.
BMC Vet Res ; 20(1): 167, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38689278

RESUMO

Arginine, which is metabolized into ornithine, proline, and nitric oxide, plays an important role in embryonic development. The present study was conducted to investigate the molecular mechanism of arginine in proliferation, differentiation, and physiological function of porcine trophoblast cells (pTr2) through metabolic pathways. The results showed that arginine significantly increased cell viability (P < 0.05). The addition of arginine had a quadratic tendency to increase the content of progesterone (P = 0.06) and protein synthesis rate (P = 0.03), in which the maximum protein synthesis rate was observed at 0.4 mM arginine. Arginine quadratically increased (P < 0.05) the intracellular contents of spermine, spermidine and putrescine, as well as linearly increased (P < 0.05) the intracellular content of NO in a dose-dependent manner. Arginine showed a quadratic tendency to increase the content of putrescine (P = 0.07) and a linear tendency to increase NO content (P = 0.09) in cell supernatant. Moreover, increasing arginine activated (P < 0.05) the mRNA expressions for ARG, ODC, iNOS and PCNA. Furthermore, inhibitors of arginine metabolism (L-NMMA and DFMO) both inhibited cell proliferation, while addition of its metabolites (NO and putrescine) promoted the cell proliferation and cell cycle, the mRNA expressions of PCNA, EGF and IGF-1, and increased (P < 0.05) cellular protein synthesis rate, as well as estradiol and hCG secretion (P < 0.05). In conclusion, our results suggested that arginine could promote cell proliferation and physiological function by regulating the metabolic pathway. Further studies showed that arginine and its metabolites modulate cell function mainly through ß-catenin and mTOR pathways.


Assuntos
Arginina , Diferenciação Celular , Proliferação de Células , Serina-Treonina Quinases TOR , Trofoblastos , beta Catenina , Animais , Arginina/farmacologia , Arginina/metabolismo , Trofoblastos/efeitos dos fármacos , Trofoblastos/metabolismo , Suínos , Proliferação de Células/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Diferenciação Celular/efeitos dos fármacos , beta Catenina/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Óxido Nítrico/metabolismo , Linhagem Celular
9.
Arch Toxicol ; 98(6): 1891-1908, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38522057

RESUMO

Dexamethasone is widely used in pregnant women at risk of preterm birth to reduce the occurrence of neonatal respiratory distress syndrome and subsequently reduce neonatal mortality. Studies have suggested that dexamethasone has developmental toxicity, but there is a notable absence of systematic investigations about its characteristics. In this study, we examined the effects of prenatal dexamethasone exposure (PDE) on mother/fetal mice at different doses (0.2, 0.4, or 0.8 mg/kg b.i.d), stages (gestational day 14-15 or 16-17) and courses (single- or double-course) based on the clinical practice. Results showed that PDE increased intrauterine growth retardation rate, and disordered the serum glucose, lipid and cholesterol metabolic phenotypes, and sex hormone level of mother/fetal mice. PDE was further discovered to interfere with the development of fetal lung, hippocampus and bone, inhibits steroid synthesis in adrenal and testis, and promotes steroid synthesis in the ovary and lipid synthesis in the liver, with significant effects observed at high dose, early stage and double course. The order of severity might be: ovary > lung > hippocampus/bone > others. Correlation analysis revealed that the decreased serum corticosterone and insulin-like growth factor 1 (IGF1) levels were closely related to PDE-induced low birth weight and abnormal multi-organ development in offspring. In conclusion, this study systematically confirmed PDE-induced multi-organ developmental toxicity, elucidated its characteristics, and proposed the potential "glucocorticoid (GC)-IGF1" axis programming mechanism. This research provided an experimental foundation for a comprehensive understanding of the effect and characteristics of dexamethasone on fetal multi-organ development, thereby guiding the application of "precision medicine" during pregnancy.


Assuntos
Dexametasona , Relação Dose-Resposta a Droga , Desenvolvimento Fetal , Animais , Feminino , Gravidez , Dexametasona/toxicidade , Dexametasona/administração & dosagem , Masculino , Desenvolvimento Fetal/efeitos dos fármacos , Camundongos , Retardo do Crescimento Fetal/induzido quimicamente , Fator de Crescimento Insulin-Like I/metabolismo , Glucocorticoides/toxicidade , Glucocorticoides/administração & dosagem , Exposição Materna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente
10.
Proc Natl Acad Sci U S A ; 118(37)2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34504014

RESUMO

Many tailed bacteriophages assemble ejection proteins and a portal-tail complex at a unique vertex of the capsid. The ejection proteins form a transenvelope channel extending the portal-tail channel for the delivery of genomic DNA in cell infection. Here, we report the structure of the mature bacteriophage T7, including the ejection proteins, as well as the structures of the full and empty T7 particles in complex with their cell receptor lipopolysaccharide. Our near-atomic-resolution reconstruction shows that the ejection proteins in the mature T7 assemble into a core, which comprises a fourfold gene product 16 (gp16) ring, an eightfold gp15 ring, and a putative eightfold gp14 ring. The gp15 and gp16 are mainly composed of helix bundles, and gp16 harbors a lytic transglycosylase domain for degrading the bacterial peptidoglycan layer. When interacting with the lipopolysaccharide, the T7 tail nozzle opens. Six copies of gp14 anchor to the tail nozzle, extending the nozzle across the lipopolysaccharide lipid bilayer. The structures of gp15 and gp16 in the mature T7 suggest that they should undergo remarkable conformational changes to form the transenvelope channel. Hydrophobic α-helices were observed in gp16 but not in gp15, suggesting that gp15 forms the channel in the hydrophilic periplasm and gp16 forms the channel in the cytoplasmic membrane.


Assuntos
Bacteriófago T7/metabolismo , Bacteriófago T7/ultraestrutura , Bacteriófago T7/genética , Capsídeo/metabolismo , Proteínas do Capsídeo/metabolismo , Membrana Celular/metabolismo , Microscopia Crioeletrônica/métodos , DNA Viral/genética , Bicamadas Lipídicas/metabolismo , Modelos Moleculares , Periplasma/metabolismo , Relação Estrutura-Atividade , Transdução Genética/métodos , Proteínas Virais/metabolismo
11.
Molecules ; 29(8)2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38675672

RESUMO

The deployment of Li-S batteries in the commercial sector faces obstacles due to their low electrical conductivity, slow redox reactions, quick fading of capacity, and reduced coulombic efficiency. These issues stem from the "shuttle effect" associated with lithium polysulfides (LiPSs). In this work, a haystack-like CeO2 derived from a cerium-based metal-organic framework (Ce-MOF) is obtained for the modification of a polypropylene separator. The carbon framework and CeO2 coexist in this haystack-like structure and contribute to a synergistic effect on the restriction of LiPSs shuttling. The carbon network enhances electron transfer in the conversion of LiPSs, improving the rate performance of the battery. Moreover, CeO2 enhances the redox kinetics of LiPSs, effectively reducing the "shuttle effect" in Li-S batteries. The Li-S battery with the optimized CeO2 modified separator shows an initial discharge capacity of 870.7 mAh/g at 2 C, maintaining excellent capacity over 500 cycles. This research offers insights into designing functional separators to mitigate the "shuttle effect" in Li-S batteries.

12.
Anal Chem ; 95(47): 17372-17383, 2023 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-37963241

RESUMO

The activable NIR-based phototheranostic nanoplatform (NP) is considered an efficient and reliable tumor treatment due to its strong targeting ability, flexible controllability, minimal side effects, and ideal therapeutic effect. This work describes the rational design of a second near-infrared (NIR-II) fluorescence imaging-guided organic phototheranostic NP (FTEP-TBFc NP). The molecular-engineered phototheranostic NP has a sensitive response to glutathione (GSH), generating hydrogen sulfide (H2S) gas, and delivering ferrocene molecules in the tumor microenvironment (TME). Under 808 nm irradiation, FTEP-TBFc could not only simultaneously generate fluorescence, heat, and singlet oxygen but also greatly enhance the generation of reactive oxygen species to improve chemodynamic therapy (CDT) and photodynamic therapy (PDT) at a biosafe laser power of 0.33 W/cm2. H2S inhibits the activity of catalase and cytochrome c oxidase (COX IV) to cause the enhancement of CDT and hypothermal photothermal therapy (HPTT). Moreover, the decreased intracellular GSH concentration further increases CDT's efficacy and downregulates glutathione peroxidase 4 (GPX4) for the accumulation of lipid hydroperoxides, thus causing the ferroptosis process. Collectively, FTEP-TBFc NPs show great potential as a versatile and efficient NP for specific tumor imaging-guided multimodal cancer therapy. This unique strategy provides new perspectives and methods for designing and applying activable biomedical phototheranostics.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Microambiente Tumoral , Fotoquimioterapia/métodos , Terapia Combinada , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Imagem Óptica , Linhagem Celular Tumoral , Nanomedicina Teranóstica/métodos
13.
Cancer Immunol Immunother ; 72(12): 4399-4414, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37932426

RESUMO

Increasing evidence suggests that mucosal-associated invariant T cells (MAITs) play a crucial role in anti-tumor responses against various cancers. In this study, we investigated the immune characteristics of MAIT cells in patients with acute myeloid leukemia (AML). Using multi-parameter flow cytometry, we performed phenotypic and functional analysis of MAITs in peripheral blood or bone marrow samples collected from 131 patients with AML including 99 newly diagnosed, 18 remission, and 14 relapsed cases, as well as 69 healthy controls. We found that MAITs exhibit signs of aging and exhaustion, particularly in CD8+ MAITs subset, at newly diagnosis. MAITs exhibit an effector memory or terminally differentiated phenotype. Frequency and number of MAITs reflect AML cell genetic features, tumor burden, disease status, and treatment responsiveness. Moreover, MAITs exhibit a highly activated or even exhausted state, as indicated by upregulation of PD-1. Furthermore, impaired production of Th1-type cytokines and increased secretion of Th17-type cytokines, granzyme B, and perforin were observed in MAITs from AML patients. Additionally, MAITs shifted toward producing cytokines that promote tumor progression, such as IL-8. Lower frequency of MAITs was associated with poorer overall survival (OS), and multivariate analysis revealed that MAITs frequency < 2.12% was an independent prognostic factor affecting OS. Collectively, our findings suggest that MAITs may play a role in immune deficiency in AML, emphasizing their potential importance in AML pathogenesis and treatment. These discoveries provide a theoretical basis for the development of novel immunotherapeutic strategies in AML.


Assuntos
Leucemia Mieloide Aguda , Células T Invariantes Associadas à Mucosa , Humanos , Prognóstico , Citocinas , Células Th17
14.
Small ; 19(26): e2207995, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36942859

RESUMO

Effectively interfering energy metabolism in tumor cells and simultaneously activating the in vivo immune system to perform immune attacks are meaningful for tumor treatment. However, precisely targeted therapy is still a huge challenge. Herein, a mitochondrial-targeting phototheranostic system, FE-T nanoparticles (FE-T NPs) are developed to damage mitochondria in tumor cells and change the tumor immunosuppressive microenvironment. FE-T NPs are engineered by encapsulating the near-infrared (NIR) absorbed photosensitizer IR-FE-TPP within amphiphilic copolymer DSPE-SS-PEG-COOH for high-performing with simultaneous mitochondrial-targeting, near-infrared II (NIR-II) fluorescence imaging, and synchronous photothermal therapy (PTT) /photodynamic therapy (PDT) /immune therapy (IMT). In tumor treatment, the disulfide in the copolymer can be cleaved by excess intracellular glutathione (GSH) to release IR-FE-TPP and accumulate in mitochondria. After 808 nm irradiation, the mitochondrial localization of FE-T NPs generated reactive oxygen species (ROS), and hyperthermia, leading to mitochondrial dysfunction, photoinductive apoptosis, and immunogenic cell death (ICD). Notably, in situ enhanced PDT/PTT in vivo via mitochondrial-targeting with FE-T NPs boosts highly efficient ICD toward excellent antitumor immune response. FE-T NPs provide an effective mitochondrial-targeting phototheranostic nanoplatform for imaging-guided tumor therapy.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Terapia Combinada , Fármacos Fotossensibilizantes , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Polímeros , Mitocôndrias , Fotoquimioterapia/métodos , Linhagem Celular Tumoral , Fototerapia/métodos , Microambiente Tumoral
15.
Cell Commun Signal ; 21(1): 84, 2023 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-37095518

RESUMO

BACKGROUND: Osteoporosis is a degenerative disease characterized by reduced bone mass, with low peak bone mass being the predominant manifestation during development and having an intrauterine origin. Pregnant women at risk of preterm delivery are commonly treated with dexamethasone to promote fetal lung development. However, pregnant dexamethasone exposure (PDE) can lead to reduced peak bone mass and susceptibility to osteoporosis in offspring. In this study, we aimed to investigate the mechanism of PDE-induced low peak bone mass in female offspring from the perspective of altered osteoclast developmental programming. METHODS: 0.2 mg/kg.d dexamethasone was injected subcutaneously into rats on gestation days (GDs) 9-20. Some pregnant rats were killed at GD20 to remove fetal rat long bones, the rest were delivered naturally, and some adult offspring rats were given ice water swimming stimulation for two weeks. RESULTS: The results showed that the fetal rat osteoclast development was inhibited in the PDE group compared with the control group. In contrast, the adult rat osteoclast function was hyperactivation with reduced peak bone mass. We further found that the promoter region methylation levels of lysyl oxidase (LOX) were decreased, the expression was increased, and the production of reactive oxygen species (ROS) was raised in PDE offspring rat long bone before and after birth. Combined in vivo and in vitro experiments, we confirmed that intrauterine dexamethasone promoted the expression and binding of the glucocorticoid receptor (GR) and estrogen receptor ß (ERß) in osteoclasts and mediated the decrease of LOX methylation level and increase of expression through upregulation of 10-11 translocator protein 3 (Tet3). CONCLUSIONS: Taken together, we confirm that dexamethasone causes osteoclast LOX hypomethylation and high expression through the GR/ERß/Tet3 pathway, leading to elevated ROS production and that this intrauterine epigenetic programming effect can be carried over to postnatal mediating hyperactivation in osteoclast and reduced peak bone mass in adult offspring. This study provides an experimental basis for elucidating the mechanism of osteoclast-mediated intrauterine programming of low peak bone mass in female offspring of PDE and for exploring its early targets for prevention and treatment. Video Abstract.


Assuntos
Dexametasona , Osteoporose , Humanos , Ratos , Gravidez , Animais , Feminino , Ratos Wistar , Osteoclastos , Proteína-Lisina 6-Oxidase , Receptor beta de Estrogênio , Espécies Reativas de Oxigênio
16.
Anesthesiology ; 138(4): 364-371, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36630143

RESUMO

BACKGROUND: Chlorhexidine generally has a good safety profile. However, allergic reactions are reported with increasing frequency. In China, it is rarely reported, and its characteristics are unknown. The purpose of this study was to summarize the experience of a Chinese allergy center with chlorhexidine allergy. METHODS: The authors retrospectively reviewed all patients who underwent chlorhexidine allergy testing in the Allergy Center of West China Hospital, Sichuan University (Chengdu, China), in the period February 2018 to May 2022 (n = 43 patients) and included the patients diagnosed with chlorhexidine allergy for analysis. RESULTS: Ten patients who were diagnosed by skin prick and serum-specific immunoglobulin E tests were included. They experienced a total of 30 allergic reactions to chlorhexidine (mean ± SD, 3.0 ± 1.3). Five patients experienced six allergic reactions (6 of 30, 20%) during general or local anesthesia, and they may have been exposed to chlorhexidine via different routes. Only one allergic reaction (1 of 30, 3%) was recorded with exposure via a mouthwash. The other 23 allergic reactions (23 of 30, 77%) were caused via a skin disinfectant; the route of exposure was IV cannulation in 22 allergic reactions (22 of 23, 96%) and broken skin in one allergic reaction (1 of 23, 4%). The symptoms included a quick onset and great severity. Two patients (2 of 10, 20%) had been accidentally re-exposed to chlorhexidine after diagnosis. CONCLUSIONS: This study conducted in China showed that the majority of reactions to chlorhexidine were attributed to skin disinfectants, and IV cannulation was the most common exposure route; in general, however, chlorhexidine allergy was easily overlooked. The potential allergenicity of chlorhexidine used for skin preparation before IV cannulation or should be considered in patients who develop allergic reactions perioperatively.


Assuntos
Hipersensibilidade a Drogas , Hipersensibilidade Imediata , Hipersensibilidade , Humanos , Clorexidina/efeitos adversos , Estudos Retrospectivos , Hipersensibilidade Imediata/induzido quimicamente , Hipersensibilidade Imediata/diagnóstico , Hipersensibilidade Imediata/epidemiologia , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/epidemiologia , Hipersensibilidade a Drogas/etiologia
17.
Contact Dermatitis ; 89(6): 496-500, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37750438

RESUMO

BACKGROUND: Furazolidone is a nitrofuran antimicrobial agent used in the treatment of bacterial and protozoal infections. Hypersensitivity to furazolidone is rarely reported and only eight cases have been documented in English since 1967. OBJECTIVES: To report a 24-year-old man who developed exanthematous drug eruptions in general and swelling sensation of the hands after first dose of oral administration of medicines for Helicobacter pylori infection 7 h later, who was finally confirmed with delayed-type IV allergic reaction to furazolidone by provocation tests. And to review the existing literature. METHODS: Thorough clinical examination, prick, intradermal, and patch tests, drug provocation tests were performed in the patient. RESULTS: Skin tests of all used drugs were negative. Drug provocation tests to furazolidone resulted to be positive. CONCLUSIONS: Clinicians should be aware that furazolidone may induce delayed-type allergic reactions; diagnostic approaches should be taken to identify the responsible drug when multiple medications were used concurrently.


Assuntos
Dermatite Alérgica de Contato , Hipersensibilidade a Drogas , Infecções por Helicobacter , Helicobacter pylori , Masculino , Humanos , Adulto Jovem , Adulto , Furazolidona , Infecções por Helicobacter/complicações , Dermatite Alérgica de Contato/complicações , Hipersensibilidade a Drogas/diagnóstico , Antibacterianos
18.
Molecules ; 28(9)2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37175314

RESUMO

The large-scale implementations of lithium iron phosphate (LFP) batteries for energy storage systems have been gaining attention around the world due to their quality of high technological maturity and flexible configuration. Unfortunately, the exponential production of LFP batteries is accompanied by an annual accumulation of spent batteries and a premature consumption of the lithium resource. Recycling souring critical battery materials such as Li2CO3 is essential to reduce the supply chain risk and achieve net carbon neutrality goals. During the recovery of Li2CO3, impurity removal is the most crucial step in the hydrometallurgy process of spent LiFePO4, which determines the purity of Li2CO3. By investigating and comparing the results of impurity elimination from the purified Li+-containing liquids with strong and weak alkalis under identical pH conditions, respectively, a strategy based on an alkali mixture has been proposed. The purified Li+-containing liquid was, thereafter, concentrated and sodium carbonate was added in order to precipitate Li2CO3. As a result, a high purity Li2CO3 (99.51%) of battery grade was obtained. LiFePO4 prepared with the recovered Li2CO3 and FePO4 as raw materials also displayed a comparative high capacity and stable cycle performance to the commercial product and further verified the electrochemical activity of the recovered materials.

19.
Asian Pac J Allergy Immunol ; 41(4): 336-339, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34246215

RESUMO

BACKGROUND: Chlorhexidine and clindamycin, especially the latter, rarely cause anaphylaxis. OBJECTIVE: To report a rare case of chlorhexidine- and clindamycin-induced anaphylaxis. METHODS: Case report. RESULTS: A 21-year-old female experienced anaphylaxis after receiving intravenous clindamycin after a left big toe fracture fixation operation; she also had a similar reaction after using a mouthwash. Therefore, we suspected the culprit might be chlorhexidine, and the skin prick and serum specific IgE test results confirmed our suspicion. Then the clindamycin provocation test verified that the patient also had hypersensitivity to clindamycin. However, the allergy tests for penicillin and cefuroxime were negative. CONCLUSIONS: Only four cases of clindamycin-induced anaphylaxis have been reported, and this is the first report of clindamycin-induced anaphylaxis verified by provocation test. The patient was given clindamycin because she was incorrectly labeled as having penicillin and cephalosporin allergies during the routine allergy test. It is essential to address this problem in China.


Assuntos
Anafilaxia , Hipersensibilidade a Drogas , Feminino , Humanos , Adulto Jovem , Adulto , Clorexidina/efeitos adversos , Clindamicina/efeitos adversos , Anafilaxia/induzido quimicamente , Anafilaxia/diagnóstico , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/etiologia , Penicilinas/efeitos adversos , Testes Cutâneos
20.
New Phytol ; 236(3): 958-973, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35872572

RESUMO

Suberin in roots acts as a physical barrier preventing water/mineral losses. In Arabidopsis, root suberization is regulated by abscisic acid (ABA) and ethylene in response to nutrient stresses. ABA also mediates coordination between microbiota and root endodermis in mineral nutrient homeostasis. However, it is not known whether this regulatory system is common to plants in general, and whether there are other key molecule(s) involved. We show that serotonin acts downstream of ABA in regulating suberization in rice and Arabidopsis and negatively regulates suberization in rice roots in response to salinity. We show that ABA represses transcription of the key gene (OsT5H) in serotonin biosynthesis, thus promoting root suberization in rice. Conversely, overexpression of OsT5H or supplementation with exogenous serotonin represses suberization and reduces tolerance to salt stress. These results identify an ABA-serotonin regulatory module controlling root suberization in rice and Arabidopsis, which is likely to represent a general mechanism as ABA and serotonin are ubiquitous in plants. These findings are of significant importance to breeding novel crop varieties that are resilient to abiotic stresses and developing strategies for production of suberin-rich roots to sequestrate more CO2 , helping to mitigate the effects of climate change.


Assuntos
Arabidopsis , Oryza , Ácido Abscísico/farmacologia , Arabidopsis/fisiologia , Dióxido de Carbono/farmacologia , Etilenos/farmacologia , Regulação da Expressão Gênica de Plantas , Oryza/fisiologia , Melhoramento Vegetal , Raízes de Plantas/fisiologia , Plantas Geneticamente Modificadas , Salinidade , Tolerância ao Sal , Serotonina/farmacologia , Estresse Fisiológico , Água/farmacologia
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