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1.
Nat Immunol ; 21(11): 1430-1443, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32839607

RESUMO

Macrophages demonstrate remarkable plasticity that is essential for host defense and tissue repair. The tissue niche imprints macrophage identity, phenotype and function. The role of vascular endothelial signals in tailoring the phenotype and function of tissue macrophages remains unknown. The lung is a highly vascularized organ and replete with a large population of resident macrophages. We found that, in response to inflammatory injury, lung endothelial cells release the Wnt signaling modulator Rspondin3, which activates ß-catenin signaling in lung interstitial macrophages and increases mitochondrial respiration by glutaminolysis. The generated tricarboxylic acid cycle intermediate α-ketoglutarate, in turn, serves as the cofactor for the epigenetic regulator TET2 to catalyze DNA hydroxymethylation. Notably, endothelial-specific deletion of Rspondin3 prevented the formation of anti-inflammatory interstitial macrophages in endotoxemic mice and induced unchecked severe inflammatory injury. Thus, the angiocrine-metabolic-epigenetic signaling axis specified by the endothelium is essential for reprogramming interstitial macrophages and dampening inflammatory injury.


Assuntos
Reprogramação Celular , Metabolismo Energético , Epigênese Genética , Inflamação/etiologia , Inflamação/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Trombospondinas/genética , Animais , Biomarcadores , Reprogramação Celular/genética , Reprogramação Celular/imunologia , Modelos Animais de Doenças , Suscetibilidade a Doenças , Imunofluorescência , Inflamação/patologia , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Trombospondinas/metabolismo
2.
Immunity ; 52(3): 475-486.e5, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32164878

RESUMO

Cytosolic DNA acts as a universal danger-associated molecular pattern (DAMP) signal; however, the mechanisms of self-DNA release into the cytosol and its role in inflammatory tissue injury are not well understood. We found that the internalized bacterial endotoxin lipopolysaccharide (LPS) activated the pore-forming protein Gasdermin D, which formed mitochondrial pores and induced mitochondrial DNA (mtDNA) release into the cytosol of endothelial cells. mtDNA was recognized by the DNA sensor cGAS and generated the second messenger cGAMP, which suppressed endothelial cell proliferation by downregulating YAP1 signaling. This indicated that the surviving endothelial cells in the penumbrium of the inflammatory injury were compromised in their regenerative capacity. In an experimental model of inflammatory lung injury, deletion of cGas in mice restored endothelial regeneration. The results suggest that targeting the endothelial Gasdermin D activated cGAS-YAP signaling pathway could serve as a potential strategy for restoring endothelial function after inflammatory injury.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas de Ciclo Celular/genética , Proliferação de Células/genética , DNA Mitocondrial/genética , Células Endoteliais/metabolismo , Inflamação/genética , Nucleotidiltransferases/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Proteínas de Ciclo Celular/metabolismo , Células Cultivadas , Citosol/metabolismo , DNA Mitocondrial/metabolismo , Células Endoteliais/citologia , Células HEK293 , Humanos , Inflamação/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Nucleotídeos Cíclicos/metabolismo , Nucleotidiltransferases/metabolismo , Proteínas de Ligação a Fosfato/genética , Proteínas de Ligação a Fosfato/metabolismo , Transdução de Sinais , Proteínas de Sinalização YAP
3.
Proc Natl Acad Sci U S A ; 121(42): e2406936121, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39388269

RESUMO

Kirsten rat sarcoma virus (KRAS) mutation is associated with malignant tumor transformation and drug resistance. However, the development of clinically effective targeted therapies for KRAS-mutant cancer has proven to be a formidable challenge. Here, we report that tripartite motif-containing protein 21 (TRIM21) functions as a target of extracellular signal-regulated kinase 2 (ERK2) in KRAS-mutant colorectal cancer (CRC), contributing to regorafenib therapy resistance. Mechanistically, TRIM21 directly interacts with and ubiquitinates v-myc avian myelocytomatosis viral oncogene homolog (c-Myc) at lysine 148 (K148) via K63-linkage, enabling c-Myc to be targeted to the autophagy machinery for degradation, ultimately resulting in the downregulation of enolase 2 expression and inhibition of glycolysis. However, mutant KRAS (KRAS/MT)-driven mitogen-activated protein kinase (MAPK) signaling leads to the phosphorylation of TRIM21 (p-TRIM21) at Threonine 396 (T396) by ERK2, disrupting the interaction between TRIM21 and c-Myc and thereby preventing c-Myc from targeting autophagy for degradation. This enhances glycolysis and contributes to regorafenib resistance. Clinically, high p-TRIM21 (T396) is associated with an unfavorable prognosis. Targeting TRIM21 to disrupt KRAS/MT-driven phosphorylation using the antidepressant vilazodone shows potential for enhancing the efficacy of regorafenib in treating KRAS-mutant CRC in preclinical models. These findings are instrumental for KRAS-mutant CRC treatment aiming at activating TRIM21-mediated selective autophagic degradation of c-Myc.


Assuntos
Autofagia , Neoplasias Colorretais , Compostos de Fenilureia , Proteínas Proto-Oncogênicas c-myc , Proteínas Proto-Oncogênicas p21(ras) , Piridinas , Ribonucleoproteínas , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Humanos , Autofagia/efeitos dos fármacos , Compostos de Fenilureia/farmacologia , Animais , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Piridinas/farmacologia , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Camundongos , Ribonucleoproteínas/metabolismo , Ribonucleoproteínas/genética , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Ensaios Antitumorais Modelo de Xenoenxerto , Proteólise/efeitos dos fármacos , Mutação , Camundongos Nus
4.
Plant J ; 117(2): 464-482, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37872890

RESUMO

Rhodiola L. is a genus that has undergone rapid radiation in the mid-Miocene and may represent a typic case of adaptive radiation. Many species of Rhodiola have also been widely used as an important adaptogen in traditional medicines for centuries. However, a lack of high-quality chromosome-level genomes hinders in-depth study of its evolution and biosynthetic pathway of secondary metabolites. Here, we assembled two chromosome-level genomes for two Rhodiola species with different chromosome number and sexual system. The assembled genome size of R. chrysanthemifolia (2n = 14; hermaphrodite) and R. kirilowii (2n = 22; dioecious) were of 402.67 and 653.62 Mb, respectively, with approximately 57.60% and 69.22% of transposable elements (TEs). The size difference between the two genomes was mostly due to proliferation of long terminal repeat-retrotransposons (LTR-RTs) in the R. kirilowii genome. Comparative genomic analysis revealed possible gene families responsible for high-altitude adaptation of Rhodiola, including a homolog of plant cysteine oxidase 2 gene of Arabidopsis thaliana (AtPCO2), which is part of the core molecular reaction to hypoxia and contributes to the stability of Group VII ethylene response factors (ERF-VII). We found extensive chromosome fusion/fission events and structural variations between the two genomes, which might have facilitated the initial rapid radiation of Rhodiola. We also identified candidate genes in the biosynthetic pathway of salidroside. Overall, our results provide important insights into genome evolution in plant rapid radiations, and possible roles of chromosome fusion/fission and structure variation played in rapid speciation.


Assuntos
Glucosídeos , Fenóis , Rhodiola , Rhodiola/genética , Rhodiola/metabolismo , Vias Biossintéticas , Tamanho do Genoma , Cromossomos , Evolução Molecular
5.
Am J Physiol Cell Physiol ; 326(2): C362-C381, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38105756

RESUMO

Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, and metastasis and immunosuppression are responsible for the poor prognosis of OSCC. Previous studies have shown that poly(ADP-ribose) polymerase (PARP)1 plays a key role in the pathogenesis of OSCC. Therefore, PARP1 may serve as an important research target for the potential treatment of OSCC. Here, we aimed to investigate the role of PARP1 in the tumorigenesis of OSCC and elucidate the key molecular mechanisms of its upstream and downstream regulation in vivo and in vitro. In human OSCC tissues and cells, Toll-like receptor (TLR)9 and PD-L1 were highly expressed and PARP1 was lowly expressed. Suppression of TLR9 remarkably repressed CAL27 and SCC9 cell proliferation, migration, and invasion. After coculture, we found that low expression of TLR9 inhibited PD-L1 expression and immune escape. In addition, TLR9 regulated PD-L1 expression through the PARP1/STAT3 pathway. PARP1 mediated the effects of TLR9 on OSCC cell proliferation, migration, and invasion and immune escape. Additionally, in vivo experiments further verified that TLR9 promoted tumor growth and immune escape by inhibiting PARP1. Collectively, TLR9 activation induced immunosuppression and tumorigenesis via PARP1/PD-L1 signaling pathway in OSCC, providing important insights for subsequent in-depth exploration of the mechanism of OSCC.NEW & NOTEWORTHY In this research, we took PARP1 as the key target to explore its regulatory effect on oral squamous cell carcinoma (OSCC). The key molecular mechanisms involved in its upstream and downstream regulation were elucidated in OSCC cell lines in vitro and tumor-bearing mice in vivo, combined with clinical OSCC tissues.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Animais , Camundongos , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Receptor Toll-Like 9/genética , Receptor Toll-Like 9/metabolismo , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Transdução de Sinais , Carcinogênese/genética , Transformação Celular Neoplásica , Terapia de Imunossupressão , Linhagem Celular Tumoral , Proliferação de Células , Poli(ADP-Ribose) Polimerase-1/genética , Poli(ADP-Ribose) Polimerase-1/metabolismo
6.
Int J Cancer ; 154(11): 1979-1986, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38353428

RESUMO

Bilateral diffuse metastatic lung adenocarcinoma (BLDM-LUAD) is a special imaging pattern of lung adenocarcinoma (LUAD). We retrospectively assessed survival outcomes and co-mutation characteristics of BLDM-LUAD patients harboring epidermal growth factor receptor (EGFR) mutations who were treated with EGFR-yrosine kinase inhibitors (TKIs). From May 2016 to May 2021, among 458 patients who submitted samples for next generation sequencing (NGS) detection in 1125 patients with non-small-cell lung cancer (NSCLC), and 44 patients were diagnosed as BLDM-LUAD. In order to analyze the survival outcomes of BLDM-LUAD patients harboring EGFR mutations who were treated with EGFR-TKIs, the factors age, gender, smoking history, hydrothorax, site of EGFR mutations and EGFR-TKIs treatment were adjusted using propensity score-matching (PSM). The Kaplan-Meier survival curves and log-rank test were used to analyze progression-free survival (PFS) and overall survival (OS). The co-mutation characteristics of BLDM-LUAD patients harboring EGFR mutations were analyzed by NGS panels. 64 patients with advanced lung adenocarcinoma harboring EGFR mutations and first-line treatment of EGFR-TKIs were successfully matched. BLDM-LUAD (n = 32) have significantly longer median PFS than control group (n = 32) (mPFS: 14 vs 6.2 months; p = .002) and insignificantly longer median OS than control group (mOS: 45 vs 25 months; p = .052). The patients with BLDM-LUAD have the higher frequency of EGFR mutation than control group (84.1% vs 62.0%) before PSM. The co-mutation genes kirsten rat sarcoma viral oncogene homolog (KRAS) (9.4%), ataxia telangiectasia-mutated (ATM) (7.4%) and mesenchymal-epithelial transition (MET) (3.1%) only appeared in the control group after PSM. The BLDM-LUAD harboring EGFR mutations was associated with a favorable prognosis to EGFR-TKI.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Neoplasias Pulmonares , Humanos , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Mutação , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos
7.
Crit Rev Eukaryot Gene Expr ; 34(2): 33-43, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38073440

RESUMO

Cervical cancer is a common malignancy among women worldwide. Long non-coding RNAs (lncRNAs) are frequently involved in the pathogenesis of cervical cancer. Therefore, the present study aimed to investigate the potentials of lncRNA799 in cervical cancer. mRNA and protein expression were detected by reverse transcription-quantitative polymerase chain reaction and Western blot analysis, respectively. Cellular functions were assessed using CCK-8, wound healing and transwell analysis. The binding potential of zinc finger E-box-binding homeobox 1 (ZEB1) on the promoter of lncRNA799 was predicted utilizing the JASPAR database, and was then verified by luciferase and chromatin immunoprecipitation (ChIP) assays. Furthermore, the gene interactions were assessed using RNA immunoprecipitation and co-immunoprecipitation assays. The results demonstrated that lncRNA799 was upregulated in cervical cancer cells. However, lncRNA799 deficiency suppressed the proliferation and epithelial-mesenchymal transition of cervical cancer cells. Furthermore, lncRNA799 could interact with eukaryotic translation initiation factor 4A3 to maintain the mRNA stability of transducin (ß)-like 1 X-linked receptor 1 (TBL1XR1) and promote the interaction between ZEB1 and TBL1XR1. Additionally, the results showed that ZEB1 could transcriptionally activate lncRNA799. Taken together, the present study suggested that the lncRNA799/TBL1XR1/ZEB1 axis could form a positive feedback loop in cervical cancer and could be, therefore, considered as a potential therapeutic strategy for cervical cancer.


Assuntos
MicroRNAs , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , MicroRNAs/genética , Retroalimentação , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Proteínas Repressoras/genética , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo
8.
Cancer ; 130(S17): 3054-3066, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39092590

RESUMO

Antibody-drug conjugates (ADCs) have demonstrated effectiveness in treating various cancers, particularly exhibiting specificity in targeting human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Recent advancements in phase 3 clinical trials have broadened current understanding of ADCs, especially trastuzumab deruxtecan, in treating other HER2-expressing malignancies. This expansion of knowledge has led to the US Food and Drug Administration's approval of trastuzumab deruxtecan for HER2-positive and HER2-low breast cancer, HER2-positive gastric cancer, and HER2-mutant nonsmall cell lung cancer. Concurrent with the increasing use of ADCs in oncology, there is growing concern among health care professionals regarding the rise in the incidence of interstitial lung disease or pneumonitis (ILD/p), which is associated with anti-HER2 ADC therapy. Studies on anti-HER2 ADCs have reported varying ILD/p mortality rates. Consequently, it is crucial to establish guidelines for the diagnosis and management of ILD/p in patients receiving anti-HER2 ADC therapy. To this end, a panel of Chinese experts was convened to formulate a strategic approach for the identification and management of ILD/p in patients treated with anti-HER2 ADC therapy. This report presents the expert panel's opinions and recommendations, which are intended to guide the management of ILD/p induced by anti-HER2 ADC therapy in clinical practice.


Assuntos
Imunoconjugados , Doenças Pulmonares Intersticiais , Receptor ErbB-2 , Humanos , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/induzido quimicamente , China , Imunoconjugados/uso terapêutico , Imunoconjugados/efeitos adversos , Pneumonia/tratamento farmacológico , Feminino , Consenso , Trastuzumab/uso terapêutico , Trastuzumab/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Camptotecina/análogos & derivados
9.
Small ; 20(27): e2310359, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38385806

RESUMO

Electrowetting displays (EWDs) based on microfluidics are highly sought after in the fields of electronic devices, smart homes, and information communication. However, the power supply of the EWD systems for visually engaging multi-color displays remains a big challenge. Herein, self-powered colorful dynamic display systems are developed by integrating the triboelectric nanogenerator (TENG) with the EWD device. The TENG is designed with a nanotube-patterned surface and can generate open-circuit voltages ranging from 30 to 295 V by controlling the contact area. The wetting property of the micro-droplet exhibits a response to the applied voltage, enabling the triboelectricity-triggered electrowetting-on-dielectric. Driven by the voltage of 160 V, the monochromatic EWD exhibits bright color switching from magenta to transparent with a pixel aperture ratio of 78%, and the recovery process can be rapidly completed. Furthermore, the self-powered colorful dynamic EWD system can be achieved. By selectively applying the voltage to the pixels in the three monochromatic layers that constitute the colorful EWD, the wetting properties of the fluids can be controlled, allowing for colorful dynamic display. This work contributes to the advancement of color display technology for portable and wearable electronic ink displays, indoor and outdoor sports equipment, and information communication.

10.
J Synchrotron Radiat ; 31(Pt 5): 1010-1018, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39042579

RESUMO

The damage threshold of an Au-coated flat mirror, one of the reflective optics installed on the FEL-2 beamline of the Dalian Coherent Light Source, China, upon far-UV free-electron laser irradiation is evaluated. The surface of the coating is characterized by profilometer and optical microscope. A theoretical approach of the phenomenon is also presented, by application of conventional single-pulse damage threshold calculations, a one-dimensional thermal diffusion model, as well as finite-element analysis with ANSYS.

11.
Appl Environ Microbiol ; 90(8): e0069324, 2024 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-39058040

RESUMO

Symbiotic microorganisms that reside on the host skin serve as the primary defense against pathogens in vertebrates. Specifically, the skin microbiome of bats may play a crucial role in providing resistance against Pseudogymnoascus destructans (Pd), the pathogen causing white-nose syndrome. However, the epidermis symbiotic microbiome and its specific role in resisting Pd in highly resistant bats in Asia are still not well understood. In this study, we collected and characterized skin microbiota samples of 19 Myotis pilosus in China and explored the differences between Pd-positive and negative individuals. We identified inhibitory effects of these bacteria through cultivation methods. Our results revealed that the Simpson diversity index of the skin microbiota for positive individuals was significantly lower than that of negative individuals, and the relative abundance of Pseudomonas was significantly higher in positive bats. Regardless of whether individuals were positive or negative for Pd, the relative abundance of potentially antifungal genera in skin microbiota was high. Moreover, we successfully isolated 165 microbes from bat skin and 41 isolates from positive individuals able to inhibit Pd growth compared to only 12 isolates from negative individuals. A total of 10 genera of Pd-inhibiting bacteria were screened, among which the genera Algoriella, Glutamicibacter, and Psychrobacter were newly discovered as Pd-inhibiting genera. These Pd-inhibiting bacteria metabolized a variety of volatile compounds, including dimethyl trisulfide, dimethyl disulfide, propylene sulfide, 2-undecanone, and 2-nonanone, which were able to completely inhibit Pd growth at low concentrations.IMPORTANCERecently, white-nose syndrome has caused the deaths of millions of hibernating bats, even threatening some with regional extinction. Bats in China with high resistance to Pseudogymnoascus destructans can provide a powerful reference for studying the management of white-nose syndrome and understanding the bats against the pathogen's intrinsic mechanisms. This study sheds light on the crucial role of host symbiotic skin microorganisms in resistance to pathogenic fungi and highlights the potential for harnessing natural defense mechanisms for the prevention and treatment of white-nose syndrome. In addition, this may also provide promising candidates for the development of bioinsecticides and fungicides that offer new avenues for addressing fungal diseases in wildlife and agricultural environments.


Assuntos
Ascomicetos , Bactérias , Quirópteros , Hibernação , Microbiota , Pele , Quirópteros/microbiologia , Animais , Pele/microbiologia , Ascomicetos/isolamento & purificação , Ascomicetos/fisiologia , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética , China , Simbiose
12.
BMC Microbiol ; 24(1): 160, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724904

RESUMO

BACKGROUND: Antibiotic-associated diarrhea (AAD) refers to symptoms of diarrhea that cannot be explained by other causes after the use of antibiotics. AAD is thought to be caused by a disruption of intestinal ecology due to antibiotics. Fecal Microbiota Transplantation (FMT) is a treatment method that involves transferring microbial communities from the feces of healthy individuals into the patient's gut. METHOD: We selected 23 AAD patients who received FMT treatment in our department. Before FMT, we documented patients' bowel movement frequency, abdominal symptoms, routine blood tests, and inflammatory markers, and collected fecal samples for 16S rRNA sequencing to observe changes in the intestinal microbiota. Patients' treatment outcomes were followed up 1 month and 3 months after FMT. RESULTS: Out of the 23 AAD patients, 19 showed a clinical response to FMT with alleviation of abdominal symptoms. Among them, 82.61% (19/23) experienced relief from diarrhea, 65% (13/20) from abdominal pain, 77.78% (14/18) from abdominal distension, and 57.14% (4/7) from bloody stools within 1 month after FMT. Inflammatory markers IL-8 and CRP significantly decreased after FMT, but there were no noticeable changes in WBC, IL-6, and TNF-α before and after transplantation. After FMT, the abundance of Bacteroides and Faecalibacterium increased in patients' fecal samples, while the abundance of Escherichia-Shigella and Veillonella decreased. CONCLUSION: FMT has a certain therapeutic effect on AAD, and can alleviate abdominal symptoms and change the intestinal microbiota of patients.


Assuntos
Antibacterianos , Diarreia , Transplante de Microbiota Fecal , Fezes , Microbioma Gastrointestinal , RNA Ribossômico 16S , Humanos , Diarreia/microbiologia , Diarreia/terapia , Transplante de Microbiota Fecal/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Antibacterianos/efeitos adversos , Fezes/microbiologia , Adulto , RNA Ribossômico 16S/genética , Idoso , Resultado do Tratamento , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética
13.
Inorg Chem ; 63(38): 17478-17487, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39229693

RESUMO

Metalo hydrogen-bonded organic frameworks (MHOFs) have received growing interest in designing crystalline functional materials. However, reports on bifunctional MHOFs showing magnetic and proton-conductive properties are extremely limited and their design is challenging. Herein, we investigated the magnetic and proton-conductive properties of two sulfonated CoHOF and MnHOF, {M(H2O)2(abs)2}n (M = Co2+ and Mn2+, Habs = 4-aminoazobenzene-4'-sulfonic anion), constructed by coordination chains. The supramolecular frameworks sustained by H bonds between -SO3- and coordinated water show directional ladder-type H bonds with hydrophilic nanochannels, leading to high proton conduction with exceptionally high conductivity around 10-2 S cm-1 at 100 °C under 97% relative humidity. In particular, the maximum σ value of CoHOF, 2.11 × 10-2 S cm-1, recorded the highest value among the reported proton-conducting materials showing slow magnetic relaxation. Meanwhile, the molecular structure of organosulfonate enables the magnetic isolation of high-spin Co2+ and Mn2+ centers in the frameworks. Magnetic measurements indicated that the MHOFs show field-induced single-ion magnet (SIM) properties, making these compounds rare magnetic-proton-conductive MHOFs. The work provides not only two unique MHOFs with SIM behavior and high proton conduction performance but also avenues for designing stable bifunctional MHOFs via a coordination chain approach.

14.
BMC Infect Dis ; 24(1): 173, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326761

RESUMO

BACKGROUND: Sepsis not only causes inflammation, but also damages the heart and increases the risk of death. The glycolytic pathway plays a crucial role in the pathogenesis of sepsis-induced cardiac injury. This study aims to investigate the value of bisphosphoglycerate mutase (BPGM), an intermediate in the glycolytic pathway, in evaluating cardiac injury in septic patients and predicting poor prognosis in sepsis. METHODS: This prospective study included 85 patients with sepsis. Serum BPGM was measured at the time of enrollment, and the patients were divided into a BPGM-positive group (n = 35) and a BPGM-negative group (n = 50) according to their serum BPGM levels. Baseline clinical and echocardiographic parameters, and clinical outcomes were analyzed and compared between the two groups. Kaplan-Meier analysis was used to compare the 28-day survival rate between BPGM-negative and BPGM-positive patients. Multivariate logistic regression analysis was conducted to explore the independent risk factors for 28-day mortality in septic patients. The predictive value of serum BPGM for sepsis-induced myocardial injury and poor prognosis in sepsis was evaluated using receiver operating characteristic (ROC)curve analysis. RESULT: The serum level of BPGM was significantly higher in patients who died within 28 days compared to survivors (p < 0.001). Kaplan-Meier analysis showed that serum BPGM-positive sepsis patients had a significantly shorter 28-day survival time (p < 0.001). Multivariate logistic regression analysis showed that serum BPGM (OR = 9.853, 95%CI 1.844-52.655, p = 0.007) and left ventricular ejection fraction-simpson(LVEF-S) (OR = 0.032, 95% CI 0.002-0.43, p = 0.009) were independent risk factors for 28-day mortality in sepsis patients. Furthermore, BPGM levels was negatively correlated with LVEF-S (p = 0.005) and positively correlated with the myocardial performance (Tei) index (p < 0.001) in sepsis patients. ROC curve analysis showed that serum BPGM was a good predictor of septic myocardial injury and 28-day mortality in sepsis patients. CONCLUSION: The level of BPGM in the serum of sepsis patients can serve as a monitoring indicator for myocardial injury, with its high level indicating the occurrence of secondary myocardial injury events and adverse outcomes in sepsis patients.


Assuntos
Cardiomiopatias , Sepse , Humanos , Bisfosfoglicerato Mutase , Volume Sistólico , Estudos Prospectivos , Função Ventricular Esquerda , Prognóstico , Estudos de Coortes , Curva ROC , Estudos Retrospectivos
15.
Acta Pharmacol Sin ; 45(6): 1142-1159, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38409216

RESUMO

Alzheimer's disease (AD), a progressive neurodegenerative disorder, is the most common cause of dementia in elderly people and substantially affects patient quality of life. Oxidative stress is considered a key factor in the development of AD. Nrf2 plays a vital role in maintaining redox homeostasis and regulating neuroinflammatory responses in AD. Previous studies show that potassium 2-(1-hydroxypentyl)-benzoate (PHPB) exerts neuroprotective effects against cognitive impairment in a variety of dementia animal models such as APP/PS1 transgenic mice. In this study we investigated whether PHPB ameriorated the progression of AD by reducing oxidative stress (OS) damage. Both 5- and 13-month-old APP/PS1 mice were administered PHPB (100 mg·kg-1·d-1, i.g.) for 10 weeks. After the cognition assessment, the mice were euthanized, and the left hemisphere of the brain was harvested for analyses. We showed that 5-month-old APP/PS1 mice already exhibited impaired performance in the step-down test, and knockdown of Nrf2 gene only slightly increased the impairment, while knockdown of Nrf2 gene in 13-month-old APP/PS1 mice resulted in greatly worse performance. PHPB administration significantly ameliorated the cognition impairments and enhanced antioxidative capacity in APP/PS1 mice. In addition, PHPB administration significantly increased the p-AKT/AKT and p-GSK3ß/GSK3ß ratios and the expression levels of Nrf2, HO-1 and NQO-1 in APP/PS1 mice, but these changes were abolished by knockdown of Nrf2 gene. In SK-N-SH APPwt cells and primary mouse neurons, PHPB (10 µM) significantly increased the p-AKT/AKT and p-GSK3ß/GSK3ß ratios and the level of Nrf2, which were blocked by knockdown of Nrf2 gene. In summary, this study demonstrates that PHPB exerts a protective effect via the Akt/GSK3ß/Nrf2 pathway and it might be a promising neuroprotective agent for the treatment of AD.


Assuntos
Doença de Alzheimer , Modelos Animais de Doenças , Transtornos da Memória , Camundongos Transgênicos , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Transdução de Sinais , Animais , Fator 2 Relacionado a NF-E2/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Camundongos , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Masculino , Humanos , Camundongos Endogâmicos C57BL
16.
Surg Endosc ; 38(8): 4731-4744, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39009728

RESUMO

BACKGROUND: The advancement of laparoscopic technology has broadened the application of laparoscopic pancreaticoduodenectomy (LPD) for treating pancreatic head and ampullary tumors. Despite its benefits, postoperative pancreatic fistula (POPF) and postpancreatectomy hemorrhage (PPH) remain significant complications. Ligamentum teres hepatis wrapping around the gastroduodenal artery (GDA) stump show limitations in reducing POPF and PPH. METHODS: This study retrospectively analyzed patients undergoing LPD from January 2016 to October 2023, We compared the effectiveness of the two-parts wrapping (the ligamentum teres hepatis wrapping of the gastroduodenal artery stump and the omentum flap wrapping of the pancreatojejunal anastomosis) and ligamentum teres hepatis wrapping around the gastroduodenal artery (GDA) in reducing postoperative pancreatic fistula (POPF) and postpancreatectomy hemorrhage (PPH), using propensity score matching for the analysis. RESULTS: A total of 172 patients were analyzed, showing that the two-parts wrapping group significantly reduced the rates of overall and severe complications, POPF, and PPH compared to ligamentum teres hepatis wrapping around the GDA group. Specifically, the study found lower rates of grade B/C POPF and no instances of PPH in the two-parts wrapping group, alongside shorter postoperative hospital stays and drainage removal times. These benefits were particularly notable in patients with soft pancreatic textures and pancreatic duct diameters of < 3 mm. CONCLUSION: The two-parts wrapping technique significantly reduce the risks of POPF and PPH in LPD, offering a promising approach for patients with soft pancreas and pancreatic duct diameter of < 3 mm.


Assuntos
Laparoscopia , Fístula Pancreática , Pancreaticoduodenectomia , Complicações Pós-Operatórias , Humanos , Pancreaticoduodenectomia/métodos , Pancreaticoduodenectomia/efeitos adversos , Masculino , Feminino , Estudos Retrospectivos , Laparoscopia/métodos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Idoso , Fístula Pancreática/prevenção & controle , Fístula Pancreática/etiologia , Hemorragia Pós-Operatória/prevenção & controle , Hemorragia Pós-Operatória/etiologia , Neoplasias Pancreáticas/cirurgia , Resultado do Tratamento , Retalhos Cirúrgicos
17.
BMC Public Health ; 24(1): 908, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38539176

RESUMO

BACKGROUND: As the internet develops and 5G technology becomes increasingly prominent, the internet has become a major source of health-related information. Increasingly, people use the internet to find health-related information, and digital health literacy is now a set of essential capabilities to improve their health in the digital era. However, little is known about the factors that influencing digital health literacy. This study aimed to assess digital health literacy scores and identify its influencing factors among internet users in China. Additionally, this study explored the participant's actual skills using an additional set of performance-based items from the Digital Health Literacy Instrument (DHLI). METHODS: An online cross-sectional study was conducted in August 2022. Participants aged ≥18 years were recruited to complete the survey. Data were collected using the Chinese revised version of the DHLI, the self-reported internet use questionnaire, and the sociodemographic questionnaire. We conducted multivariate linear regression analyses to explore the relationships among the sociodemographic variables, behavior of internet use, and the digital health literacy scores. RESULTS: In total, 702 participants completed the survey. The mean DHLI score was 2.69 ± 0.61. Multivariate linear regression analyses showed that the age groups 35-49 (ß = - 0.08, P = 0.033), 50-64 (ß = - 0.161, P < 0.001), and ≥ 65 (ß = - 0.138, P < 0.001) were negatively associated with DHL scores. However, education level, including bachelor's or associate degree (ß = 0.255, P = 0.002) and master's degree and above (ß = 0.256, P < 0.001), frequency of health-related Internet usage (ß = 0.192, P < 0.001), the number of digital devices used (ß = 0.129, P = 0.001), and OHISB (ß = 0.103, P = 0.006) showed a positive relationship with DHL scores. CONCLUSIONS: The study findings demonstrate that age, educational levels, number of technological devices used, and greater use of the web for health information were independently associated with DHL scores. Healthcare providers should consider providing training programs tailored to specific sociodemographic factors to improve the ability that find and use accurate information online to meet digital health services, which contributes to enhance their self-management and reduce health disparities.


Assuntos
Letramento em Saúde , Telemedicina , Humanos , Adolescente , Adulto , Saúde Digital , Estudos Transversais , Inquéritos e Questionários , Internet , China
18.
J Asian Nat Prod Res ; 26(2): 228-236, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38193237

RESUMO

A novel [1, 2, 4]triazolo[5,1-b]quinazoline fluorescent probe (VIi) for Fe3+ was developed, featuring with rapid response (< 5 s) and specific selectivity to Fe3+, low detection limit (1.3 × 10-5 M), as well as the ability to resist interference of chelating agent (e.g. EDTA). VIi-based fluorescent test paper can quickly recognize Fe3+ under irradiation at the wavelength of 365 nm. The fluorescence probe VIi has potential application prospects for the detection of Fe3+ in real circumstance.


Assuntos
Corantes Fluorescentes , Quinazolinas , Espectrometria de Fluorescência , Íons
19.
Int Orthop ; 2024 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-39340642

RESUMO

PURPOSE: To evaluate the influence of patellar morphology on functional outcomes and patellofemoral joint alignment after unicompartmental knee arthroplasty (UKA). METHODS: This study retrospectively analyzed the clinical and imaging data of 207 patients with osteoarthritis of the unicompartment of the knee who underwent UKA between September 2020 and April 2023. Patients were divided into three groups according to the Wiberg classification: group W1 (I, n = 47), group W2 (II, n = 117), and group W3 (III, n = 43). Knee function was assessed using the Hospital for Specialty Surgery (HSS) knee score and Feller patellar score, and the incidence of anterior knee pain after surgery was recorded and compared. Imaging parameters such as patellar tilt angle (PTA), lateral patellofemoral angle (LPA) and Insall-Salvati ratio (ISR) were measured to assess patellofemoral joint alignment. RESULTS: The HSS scores of the three groups were not statistically different; the postoperative Feller scores of the group W3 differed significantly from those of the other two groups. The incidence of early postoperative anterior knee pain was higher in the group W3 than in the other two groups. The difference between preoperative PTA, postoperative PTA and preoperative LPA in the group W3 and the other two groups was statistically significant. CONCLUSION: Patients with Wiberg III patellae exhibited worse patellar scores, as well as more anterior knee pain and patellar tilt postoperatively. This finding highlights the need for individualized treatment to the Wiberg III patella during UKA to enhance surgical outcomes.

20.
Int Orthop ; 48(10): 2579-2588, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38691141

RESUMO

BACKGROUND: Patients with dysplasia of the hip (DDH) have different degrees of bone defects above and outside the acetabulum, and anatomically reconstructing the acetabular centre of rotation is difficult in primary total hip arthroplasty (THA). METHODS: From April 2012 to December 2022, 64 patients (64 hips) with DDH treated with THA with structural bone graft in the superolateral acetabulum were selected. The Oxford hip score(OHS), Barthel index (BI), leg length discrepancy, Wibegr central edge-angle(CE), gluteus medius muscle strength, vertical and horizontal distance of the hip rotation center, coverage rate of the bone graft and complications were used to evaluate the clinical effectiveness of the patients. RESULTS: All patients were followed up for an average of 7.3±1.9 years. The OHS improved significantly after the operation (P<0.001). The postoperative BI was significantly greater than that before operation (P<0.001). The postoperative leg length discrepancy was significantly lower than that before the operation (P<0.001). Postoperative bedside photography revealed that the height and horizontal distance to the hip rotation center were significantly lower after surgery than before surgery (P<0.001). The postoperative CE was significantly greater than that before surgery (P<0.001). No acetabular component loosening or bone graft resorption was found during the postoperative imaging examination. CONCLUSIONS: The use of biological acetabular cup combined with structural bone graft in the superolateral acetabulum in THA for DDH can obtain satisfactory medium and long-term clinical and radiological results.


Assuntos
Acetábulo , Artroplastia de Quadril , Transplante Ósseo , Humanos , Feminino , Masculino , Artroplastia de Quadril/métodos , Transplante Ósseo/métodos , Pessoa de Meia-Idade , Acetábulo/cirurgia , Resultado do Tratamento , Adulto , Idoso , Seguimentos , Articulação do Quadril/cirurgia , Articulação do Quadril/fisiopatologia , Articulação do Quadril/diagnóstico por imagem , Estudos Retrospectivos , Desigualdade de Membros Inferiores/cirurgia , Desigualdade de Membros Inferiores/etiologia
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