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1.
Nature ; 577(7792): 636-640, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31959986

RESUMO

Dualities are mathematical mappings that reveal links between apparently unrelated systems in virtually every branch of physics1-8. Systems mapped onto themselves by a duality transformation are called self-dual and exhibit remarkable properties, as exemplified by the scale invariance of an Ising magnet at the critical point. Here we show how dualities can enhance the symmetries of a dynamical matrix (or Hamiltonian), enabling the design of metamaterials with emergent properties that escape a standard group theory analysis. As an illustration, we consider twisted kagome lattices9-15, reconfigurable mechanical structures that change shape by means of a collapse mechanism9. We observe that pairs of distinct configurations along the mechanism exhibit the same vibrational spectrum and related elastic moduli. We show that these puzzling properties arise from a duality between pairs of configurations on either side of a mechanical critical point. The critical point corresponds to a self-dual structure with isotropic elasticity even in the absence of spatial symmetries and a twofold-degenerate spectrum over the entire Brillouin zone. The spectral degeneracy originates from a version of Kramers' theorem16,17 in which fermionic time-reversal invariance is replaced by a hidden symmetry emerging at the self-dual point. The normal modes of the self-dual systems exhibit non-Abelian geometric phases18,19 that affect the semiclassical propagation of wavepackets20, leading to non-commuting mechanical responses. Our results hold promise for holonomic computation21 and mechanical spintronics by allowing on-the-fly manipulation of synthetic spins carried by phonons.

2.
Circulation ; 147(18): 1369-1381, 2023 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-36870065

RESUMO

BACKGROUND: Computed tomography-derived fractional flow reserve (CT-FFR) using on-site machine learning enables identification of both the presence of coronary artery disease and vessel-specific ischemia. However, it is unclear whether on-site CT-FFR improves clinical or economic outcomes when compared with the standard of care in patients with stable coronary artery disease. METHODS: In total, 1216 patients with stable coronary artery disease and an intermediate stenosis of 30% to 90% on coronary computed tomographic angiography were randomized to an on-site CT-FFR care pathway using machine learning or to standard care in 6 Chinese medical centers. The primary end point was the proportion of patients undergoing invasive coronary angiography without obstructive coronary artery disease or with obstructive disease who did not undergo intervention within 90 days. Secondary end points included major adverse cardiovascular events, quality of life, symptoms of angina, and medical expenditure at 1 year. RESULTS: Baseline characteristics were similar in both groups, with 72.4% (881/1216) having either typical or atypical anginal symptoms. A total of 421 of 608 patients (69.2%) in the CT-FFR care group and 483 of 608 patients (79.4%) in the standard care group underwent invasive coronary angiography. Compared with standard care, the proportion of patients undergoing invasive coronary angiography without obstructive coronary artery disease or with obstructive disease not undergoing intervention was significantly reduced in the CT-FFR care group (28.3% [119/421] versus 46.2% [223/483]; P<0.001). Overall, more patients underwent revascularization in the CT-FFR care group than in the standard care group (49.7% [302/608] versus 42.8% [260/608]; P=0.02), but major adverse cardiovascular events at 1 year did not differ (hazard ratio, 0.88 [95% CI, 0.59-1.30]). Quality of life and symptoms improved similarly during follow-up in both groups, and there was a trend towards lower costs in the CT-FFR care group (difference, -¥4233 [95% CI, -¥8165 to ¥973]; P=0.07). CONCLUSIONS: On-site CT-FFR using machine learning reduced the proportion of patients with stable coronary artery disease undergoing invasive coronary angiography without obstructive disease or requiring intervention within 90 days, but increased revascularization overall without improving symptoms or quality of life, or reducing major adverse cardiovascular events. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03901326.


Assuntos
Doença da Artéria Coronariana , Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico , Humanos , Doença da Artéria Coronariana/diagnóstico , Qualidade de Vida , Angiografia Coronária/métodos , Tomografia Computadorizada por Raios X , Angiografia por Tomografia Computadorizada/métodos , Angina Pectoris , Valor Preditivo dos Testes
3.
Small ; 20(29): e2310664, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38342707

RESUMO

Establishing effective charge transfer channels between two semiconductors is key to improving photocatalytic activity. However, controlling hetero-structures in situ and designing binding modes pose significant challenges. Herein, hydrolytic SnCl2·2H2O is selected as the metal source and loaded in situ onto a layered carbon nitriden supramolecular precursor. A composite photocatalyst, S4-Sn-N2, with electron pathways of SnS2 and tubular carbon nitriden (TCN) is prepared through pyrolysis and vulcanization processes. The contact interface of SnS2-TCN is increased significantly, promoting the formation of S4-Sn-N2 micro-structure in a Z-scheme charge transfer channel. This structure accelerates the separation and transport of photogenerated carriers, maintains the stronger redox ability, and improves the stability of SnS2 in this series of heterojunctions. Therefore, the catalyst demonstrated exceptional photocatalytic hydrogen production efficiency, achieving a reaction rate of 86.4 µmol h-1, which is 3.15 times greater than that of bare TCN.

4.
J Autoimmun ; 148: 103289, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39059058

RESUMO

Patients with primary biliary cholangitis (PBC) commonly experience extrahepatic rheumatic diseases. However, the epidemiologic and genetic associations as well as causal relationship between PBC and these extrahepatic conditions remain undetermined. In this study, we first conducted systematic review and meta-analyses by analyzing 73 studies comprising 334,963 participants across 17 countries and found strong phenotypic associations between PBC and rheumatic diseases. Next, we utilized large-scale genome-wide association study summary data to define the shared genetic architecture between PBC and rheumatic diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and Sjögren's syndrome (SS). We observed significant genetic correlations between PBC and each of the four rheumatic diseases. Pleiotropy and heritability enrichment analysis suggested the involvement of humoral immunity and interferon-associated processes for the comorbidity. Of note, we identified four variants shared between PBC and RA (rs80200208), SLE (rs9843053), and SSc (rs27524, rs3873182) using cross-trait meta-analysis. Additionally, several pleotropic loci for PBC and rheumatic diseases were found to share causal variants with gut microbes possessing immunoregulatory functions. Finally, Mendelian randomization revealed consistent evidence for a causal effect of PBC on RA, SLE, SSc, and SS, but no or inconsistent evidence for a causal effect of extrahepatic rheumatic diseases on PBC. Our study reveals a profound genetic overlap and causal relationships between PBC and extrahepatic rheumatic diseases, thus providing insights into shared biological mechanisms and novel therapeutic interventions.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38830044

RESUMO

OBJECTIVES: This study aimed to investigate the value of a deep learning (DL) model based on greyscale ultrasound (US) images for precise assessment and accurate diagnosis of primary Sjögren's syndrome (pSS). METHODS: This was a multicentre prospective analysis. All pSS patients were diagnosed according to 2016 ACR/EULAR criteria. 72 pSS patients and 72 sex- and age-matched healthy controls recruited between January 2022 and April 2023, together with 41 patients and 41 healthy controls recruited from June 2023 to February 2024 were used for DL model development and validation, respectively. DL model was constructed based on the ResNet 50, input with preprocessed all participants' bilateral submandibular glands (SMGs), parotid glands (PGs), and lacrimal glands (LGs) greyscale US images. Diagnostic performance of the model was compared with two radiologists. The accuracy of prediction and identification performance of DL model were evaluated by calibration curve. RESULTS: 864 and 164 greyscale US images of SMGs, PGs, and LGs were collected for development and validation of the model. The AUCs of DL model in the SMG, PG, and LG were 0.92, 0.93, 0.91 in the model cohort, and were 0.90, 0.88, 0.87 in the validation cohort respectively, outperforming both radiologists. Calibration curves showed the prediction probability of DL model were consistent with the actual probability in both model cohort and validation cohort. CONCLUSION: DL model based on greyscale US images showed diagnostic potential in the precise assessment of pSS patients in the SMG, PG, and LG, outperforming conventional radiologist evaluation.

6.
Cardiovasc Diabetol ; 23(1): 270, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39044255

RESUMO

BACKGROUND: A significant percentage of patients with acute coronary syndrome (ACS) without standard modifiable cardiovascular risk factors (SMuRFs) are being identified. Nonetheless, the prognostic influence of the TyG index on adverse events in this type of patient remains unexplored. The aim of this study was to assess the prognostic value of the TyG index among ACS patients without SMuRFs for predicting adverse outcomes. METHODS: This study involved 1140 consecutive patients who were diagnosed with ACS without SMuRFs at Beijing Anzhen Hospital between May 2018 and December 2020 and underwent coronary angiography. Each patient was followed up for a period of 35 to 66 months after discharge. The objective of this study was to examine major adverse cardiac and cerebrovascular events (MACCE), which included all-cause mortality, non-fatal myocardial infarction, non-fatal ischemic stroke, as well as ischemia-driven revascularization. RESULTS: During the median follow-up period of 48.3 months, 220 (19.3%) MACCE events occurred. The average age of the participants was 59.55 ± 10.98 years, and the average TyG index was 8.67 ± 0.53. In the fully adjusted model, when considering the TyG index as either a continuous/categorical variable, significant associations with adverse outcomes were observed. Specifically, for each 1 standard deviation increase in the TyG index within the highest TyG index group, there was a hazard ratio (HR) of 1.245 (95% confidence interval CI 1.030, 1.504) for MACCE and 1.303 (95% CI 1.026, 1.653) for ischemia-driven revascularization (both P < 0.05), when the TyG index was analyzed as a continuous variable. Similarly, when the TyG index was examined as a categorical variable, the HR (95% CI) for MACCE in the highest TyG index group was 1.693 (95% CI 1.051, 2.727) (P < 0.05) in the fully adjusted model, while the HR (95% CI) for ischemia-driven revascularization was 1.855 (95% CI 0.998, 3.449) (P = 0.051). Additionally, the TyG index was found to be associated with a poor prognosis among the subgroup. CONCLUSION: The TyG index is correlated with poor prognosis in patients with ACS without SMuRFs, suggesting that it may be an independent predictive factor of adverse events among these individuals.


Assuntos
Síndrome Coronariana Aguda , Biomarcadores , Glicemia , Valor Preditivo dos Testes , Triglicerídeos , Humanos , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/mortalidade , Síndrome Coronariana Aguda/diagnóstico , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Medição de Risco , Prognóstico , Biomarcadores/sangue , Triglicerídeos/sangue , Fatores de Tempo , Pequim/epidemiologia , Glicemia/metabolismo , Fatores de Risco de Doenças Cardíacas , Estudos Retrospectivos , Angiografia Coronária
7.
Cardiovasc Diabetol ; 23(1): 267, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39039597

RESUMO

BACKGROUND: Sodium-Glucose Cotransporter-2 Inhibitor (SGLT2i) is a novel oral drug for treating type 2 diabetes mellitus (T2DM) with demonstrated cardiovascular benefits. Previous studies in apolipoprotein E knockout mice have shown that SGLT2i is associated with attenuated progression of atherosclerosis. However, whether this effect extends to T2DM patients with coronary atherosclerosis in real-world settings remains unknown. METHODS: In this longitudinal cohort study using coronary computed tomography angiography (CCTA), T2DM patients who underwent ≥ 2 CCTA examinations at our center between 2019 and 2022 were screened. Eligible patients had multiple study plaques, defined as non-obstructive stenosis at baseline and not intervened during serial CCTAs. Exclusion criteria included a CCTA time interval < 12 months, prior SGLT2i treatment, or initiation/discontinuation of SGLT2i during serial CCTAs. Plaque volume (PV) and percent atheroma volume (PAV) were measured for each study plaque using CCTA plaque analysis software. Patients and plaques were categorized based on SGLT2i therapy and compared using a 1:1 propensity score matching (PSM) analysis. RESULTS: The study included 236 patients (mean age 60.5 ± 9.5 years; 69.1% male) with 435 study plaques (diameter stenosis ≥ 50%, 31.7%). Following SGLT2i treatment for a median duration of 14.6 (interquartile range: 13.0, 20.0) months, overall, non-calcified, and low-attenuation PV and PAV were significantly decreased, while calcified PV and PAV were increased (all p < 0.001). Meanwhile, reductions in overall PV, non-calcified PV, overall PAV, and non-calcified PAV were significantly greater in SGLT2i-treated compared to non-SGLT2i-treated plaques (all p < 0.001). PSM analysis showed that SGLT2i treatment was associated with higher reductions in overall PV (- 11.77 mm3 vs. 4.33 mm3, p = 0.005), non-calcified PV (- 16.96 mm3 vs. - 1.81 mm3, p = 0.017), overall PAV (- 2.83% vs. 3.36%, p < 0.001), and non-calcified PAV (- 4.60% vs. 0.70%, p = 0.003). These findings remained consistent when assessing annual changes in overall and compositional PV and PAV. Multivariate regression models demonstrated that SGLT2i therapy was associated with attenuated progression of overall or non-calcified PV or PAV, even after adjusting for cardiovascular risk factors, medications, and baseline overall or non-calcified PV or PAV, respectively (all p < 0.05). The effect of SGLT2i on attenuating non-calcified plaque progression was consistent across subgroups (all p for interaction > 0.05). CONCLUSIONS: In this longitudinal CCTA cohort of T2DM patients, SGLT2i therapy markedly regressed coronary overall PV and PAV, mainly result from a significant reduction in non-calcified plaque.


Assuntos
Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana , Diabetes Mellitus Tipo 2 , Placa Aterosclerótica , Valor Preditivo dos Testes , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Masculino , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Feminino , Pessoa de Meia-Idade , Estudos Longitudinais , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/diagnóstico , Idoso , Resultado do Tratamento , Fatores de Tempo , Estudos Retrospectivos , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/efeitos dos fármacos
8.
Eur J Clin Invest ; 54(2): e14100, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37776036

RESUMO

BACKGROUND: Systemic immune-inflammation index (SII) is a novel inflammatory marker based on neutrophils, platelets and lymphocytes counts, which has potential prognostic value among coronary artery disease (CAD) patients as described by some observational studies. We aimed to provide higher-certainty evidence to verify the association of SII with poor outcomes of CAD patients. METHODS: PubMed, Web of Science, Embase, Ovid and Scopus were searched to find relevant literature exploring the prognostic value of SII among CAD patients. Hazard ratios (HRs) with 95% confidence intervals (CIs) extracted from the literature included were pooled with the fixed-effect or random-effect model. Sensitivity analyses and subgroup analyses were conducted to detect the source of heterogeneity and evaluate the stability of results. RESULTS: A total of nine studies with 15,832 participants were included. The quantitative synthesis including eight studies with 15,657 participants showed that the high SII was related to the major adverse cardiovascular event in CAD patients (HR with 95% CI: 2.36 [1.67, 3.33]). After eliminating heterogeneity and adjusting for publication bias, the above result was still robust (HR with 95% CI: 1.67 [1.32, 2.12]). Additionally, we also demonstrated the prognostic values of SII for all-cause death, cardiovascular death, myocardial infarction and stroke. CONCLUSION: Higher SII has prognostic values for adverse outcomes in CAD patients.


Assuntos
Doença da Artéria Coronariana , Infarto do Miocárdio , Humanos , Prognóstico , Plaquetas , Inflamação
9.
Rev Cardiovasc Med ; 25(3): 88, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-39076953

RESUMO

Background: Deferred stenting has been recognized as beneficial for patients with acute ST-segment elevation myocardial infarction (STEMI) accompanied by a high thrombus burden. Nevertheless, its efficacy and safety specifically in geriatric STEMI patients remain to be elucidated. This study aims to bridge this knowledge gap and assess the potential advantages of deferred stenting in an older patient cohort. Methods: In this study, 208 geriatric patients (aged ≥ 80 years) with STEMI and a high thrombus burden in the infarct-related artery (IRA) were enrolled. They were categorized into two groups: the deferred stenting group, where stent implantation was conducted after 7-8 days of continuous antithrombotic therapy, and the immediate stenting group, where stent implantation was performed immediately. Results: In the deferred stenting group, the stents used were significantly larger in diameter and shorter in length compared to those in the immediate stenting group (p < 0.05). This group also exhibited a lower incidence of distal embolism in the IRA, and higher rates of the thrombolysis in myocardial infarction (TIMI) blood flow grade 3 and myocardial blush grade 3 (p < 0.05). Additionally, the left ventricular ejection fractions at the 1-year follow-up were significantly higher in the deferred stenting group than in the immediate stenting group (p < 0.05). The rate of the major adverse cardiac events in the deferred stenting group was significantly lower than in the immediate stenting groups (p < 0.05). Conclusions: Deferred stenting for geriatric patients with STEMI and high thrombus burden demonstrates significant clinical benefits. This approach not only reduces the incidence of distal embolism in the IRA, but also enhances myocardial tissue perfusion and preserves cardiac ejection function. Moreover, deferred stenting has proven to be safe in this patient population, indicating its potential as a preferred treatment strategy in such cases.

10.
Opt Lett ; 49(9): 2213-2216, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691682

RESUMO

Optical vortex (OV) modulation is a powerful technique for enhancing the intrinsic degrees-of-freedom in structured light applications. Particularly, the lattices involving multiple OVs have garnered significant academic interest owing to their wide applicability in optical tweezers and condensed matter physics. However, all OVs in a lattice possess the same order, which cannot be modulated individually, limiting its versatile application. Herein, we propose, to our knowledge, a novel concept, called the hot-swap method, to design a switchable hybrid-order OV lattice, in which each OV is easily replaced by arbitrary orders. We experimentally generated the switchable hybrid-order OV lattice and studied its characteristics, including interferograms, retrieved phase, energy flow, and orbital angular momentum. Furthermore, the significant advantages of the switchable hybrid-order OV lattice are demonstrated through the independent manipulation of multiple yeast cells. This study provides a novel scheme for accurate control and modulation of OV lattices, which greatly facilitates the diverse applications of optical manipulation and particle trapping and control.

11.
BMC Gastroenterol ; 24(1): 72, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355421

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is gradually becoming a huge threat to public health. With complex working characteristics, female nurses had been found with high risk of NAFLD. To develop and validate a prediction model to predict the prevalence of NAFLD based on demographic characteristics, work situation, daily lifestyle and laboratory tests in female nurses. METHODS: This study was a part of the Chinese Nurse Cohort Study (The National Nurse Health Study, NNHS), and data were extracted from the first-year follow data collected from 1st June to 1st September 2021 by questionnaires and physical examination records in a comprehensive tertiary hospital. The questionnaires included demographic characteristics, work situation and daily lifestyle. Logistic regression and a nomogram were used to develop and validate the prediction model. RESULTS: A total of 824 female nurses were included in this study. Living situation, smoking history, monthly night shift, daily sleep time, ALT/AST, FBG, TG, HDL-C, UA, BMI, TBil and Ca were independent risk factors for NAFLD occurance. A prediction model for predicting the prevalence of NAFLD among female nurses was developed and verified in this study. CONCLUSION: Living situation, smoking history, monthly night shift, daily sleep time, ALT/AST, FBG, TG, UA, BMI and Ca were independent predictors, while HDL-C and Tbil were independent protective indicators of NAFLD occurance. The prediction model and nomogram could be applied to predict the prevalence of NAFLD among female nurses, which could be used in health improvement. TRIAL REGISTRATION: This study was a part of the Chinese Nurse Cohort Study (The National Nurse Health Study, NNHS), which was a ambispective cohort study contained past data and registered at Clinicaltrials.gov ( https://clinicaltrials.gov/ct2/show/NCT04572347 ) and the China Cohort Consortium ( http://chinacohort.bjmu.edu.cn/project/102/ ).


Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Feminino , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Estudos de Coortes , Prevalência , Fatores de Risco , Internet , China/epidemiologia
12.
BMC Cardiovasc Disord ; 24(1): 360, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39009987

RESUMO

BACKGROUND: The atherogenic index of plasma (AIP) is considered an independent risk factor for coronary artery disease (CAD). The present study investigated whether AIP correlates with the formation of coronary collateral circulation (CCC) in CAD patients with chronic total occlusion (CTO). METHODS: This retrospective study included 1093 CAD patients with CTO confirmed by coronary angiography from January 2020 to December 2020 at Beijing Anzhen Hospital. Based on the Rentrop scoring system, the patients were divided into the good CCC group and the poor CCC group. AIP was calculated by log (triglyceride/high-density lipoprotein cholesterol). Meanwhile, the study population was further divided into four groups according to the quartiles of AIP. RESULTS: Patients in the poor CCC group exhibited significantly higher AIP compared to those in the good CCC group (0.31 ± 0.27 vs. 0.14 ± 0.24, p < 0.001). Multivariate logistic regression analysis revealed an independent association between AIP and poor CCC, regardless of whether AIP was treated as a continuous or categorical variable (p < 0.001), after adjusting for confounding factors. Besides, this association remained consistent across most subgroups. The incorporation of AIP into the baseline model significantly enhanced the accuracy of identifying poor CCC [area under the curve (AUC): baseline model, 0.661 vs. baseline model + AIP, 0.721, p for comparison < 0.001]. CONCLUSIONS: Elevated AIP is independently associated with an increased risk of poor CCC in CAD patients with CTO, and AIP may improve the ability to identify poor CCC in clinical practice.


Assuntos
Biomarcadores , Circulação Colateral , Angiografia Coronária , Circulação Coronária , Oclusão Coronária , Humanos , Masculino , Oclusão Coronária/fisiopatologia , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/sangue , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Doença Crônica , Biomarcadores/sangue , Medição de Risco , Doença da Artéria Coronariana/fisiopatologia , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico , Valor Preditivo dos Testes , Triglicerídeos/sangue , HDL-Colesterol/sangue , Fatores de Risco , Prognóstico
13.
Acta Pharmacol Sin ; 45(2): 378-390, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37798352

RESUMO

Reinforced cellular responses to endoplasmic reticulum (ER) stress are caused by a variety of pathological conditions including cancers. Human rhomboid family-1 protein (RHBDF1), a multiple transmembrane protein located mainly on the ER, has been shown to promote cancer development, while the binding immunoglobulin protein (BiP) is a key regulator of cellular unfolded protein response (UPR) for the maintenance of ER protein homeostasis. In this study, we investigated the role of RHBDF1 in maintaining ER protein homeostasis in breast cancer cells. We showed that deleting or silencing RHBDF1 in breast cancer cell lines MCF-7 and MDA-MB-231 caused marked aggregation of unfolded proteins in proximity to the ER. We demonstrated that RHBDF1 directly interacted with BiP, and this interaction had a stabilizing effect on the BiP protein. Based on the primary structural motifs of RHBDF1 involved in BiP binding, we found a pentapeptide (PE5) targeted BiP and inhibited BiP ATPase activity. SPR assay revealed a binding affinity of PE5 toward BiP (Kd = 57.7 µM). PE5 (50, 100, 200 µM) dose-dependently promoted ER protein aggregation and ER stress-mediated cell apoptosis in MCF-7 and MDA-MB-231 cells. In mouse 4T1 breast cancer xenograft model, injection of PE5 (10 mg/kg, s.c., every 2 days for 2 weeks) significantly inhibited the tumor growth with markedly increased ER stress and apoptosis-related proteins in tumor tissues. Our results suggest that the ability of RHBDF1 to maintain BiP protein stability is critical to ER protein homeostasis in breast cancer cells, and that the pentapeptide PE5 may serve as a scaffold for the development of a new class of anti-BiP inhibitors.


Assuntos
Neoplasias da Mama , Proteínas de Transporte , Humanos , Animais , Camundongos , Feminino , Proteínas de Transporte/metabolismo , Neoplasias da Mama/tratamento farmacológico , Estresse do Retículo Endoplasmático , Apoptose , Resposta a Proteínas não Dobradas , Proteínas Reguladoras de Apoptose/metabolismo , Imunoglobulinas/metabolismo , Proteínas de Membrana/metabolismo
14.
Appl Microbiol Biotechnol ; 108(1): 278, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38558151

RESUMO

The production of succinic acid from corn stover is a promising and sustainable route; however, during the pretreatment stage, byproducts such as organic acids, furan-based compounds, and phenolic compounds generated from corn stover inhibit the microbial fermentation process. Selecting strains that are resistant to stress and utilizing nondetoxified corn stover hydrolysate as a feedstock for succinic acid production could be effective. In this study, A. succinogenes CICC11014 was selected as the original strain, and the stress-resistant strain A. succinogenes M4 was obtained by atmospheric and room temperature plasma (ARTP) mutagenesis and further screening. Compared to the original strain, A. succinogenes M4 exhibited a twofold increase in stress resistance and a 113% increase in succinic acid production when hydrolysate was used as the substrate. By conducting whole-genome resequencing of A. succinogenes M4 and comparing it with the original strain, four nonsynonymous gene mutations and two upstream regions with base losses were identified. KEY POINTS: • A high-stress-resistant strain A. succinogenes M4 was obtained by ARTP mutation •  The production of succinic acid increased by 113% • The mutated genes of A. succinogenes M4 were detected and analyzed.


Assuntos
Actinobacillus , Zea mays , Zea mays/química , Ácido Succínico , Melhoramento Vegetal , Fermentação , Mutação
15.
Lipids Health Dis ; 23(1): 131, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38704561

RESUMO

BACKGROUND: In the past few years, circulating complement C1q involvement in atherosclerosis has garnered growing research interest in addition to the emerging recognition of the novel lipid marker named atherogenic index of plasma (AIP). Nevertheless, among patients experiencing low-density lipoprotein cholesterol (LDL-C) levels less than 1.8mmol/L, the interplay between C1q combined with the AIP for coronary artery disease (CAD) is ambiguous. METHODS: Patients were stratified into a non-CAD and CAD group according to their coronary angiography. The association between C1q in conjunction with the AIP and CAD was explored using restricted cubic spline analyses and logistic regression models. To assess how it predicted, a receiver operating characteristic analysis was undertaken. RESULTS: A total of 7270 patients comprised 1476 non-CAD patients and 5794 patients diagnosed with CAD were analyzed. A comparison of the two groups showed that the C1q levels were notably higher compared to the CAD group, while AIP exhibited an inverse trend. Across quartiles of C1q, the AIP demonstrated a decline with increasing C1q levels, and significant differences were observed between the groups. A correlation analysis underscored a notable negative correlation between the two variables. Univariate and multivariate logistic regression analyses revealed significant associations between CAD and the C1q quartile groups/AIP. Furthermore, compared with the Q4 group, a decrease in the C1q levels corresponded to an escalation in CAD risk, with the odds ratio rising from 1.661 to 2.314. CONCLUSIONS: In conclusion, there appears to be a notable positive correlation between the combination of C1q with the AIP and CAD.


Assuntos
LDL-Colesterol , Complemento C1q , Doença da Artéria Coronariana , Humanos , Complemento C1q/metabolismo , Masculino , Doença da Artéria Coronariana/sangue , Feminino , Pessoa de Meia-Idade , Idoso , LDL-Colesterol/sangue , Angiografia Coronária , Biomarcadores/sangue , Curva ROC , Modelos Logísticos , Aterosclerose/sangue , Fatores de Risco
16.
Artigo em Inglês | MEDLINE | ID: mdl-38607208

RESUMO

Objective: Investigate the Correlation Between the Severity of Coronary Artery Disease and Retinal Artery Disease, and assess the Efficacy of Angiotensin-Converting Enzyme Inhibitors (ACEIs) Application. Methods: One hundred patients diagnosed with primary hypertension at our hospital were chosen for the study. All patients underwent dual-source 64-layer spiral CT coronary angiography and fundus photography examination. Based on the extent of coronary artery stenosis, the patients were divided into Group A, Group B, Group C, and Group D. Results: In comparison with patients in Group A, individuals in Groups B, C, and D exhibited a notable increase in the severity of retinal artery stenosis and arteriovenous crossing signs (P < .05). Furthermore, the severity of retinal artery stenosis and arteriovenous crossing signs demonstrated an incremental trend with the severity of coronary artery stenosis (P < .05). The arteriovenous crossing sign exhibited a sensitivity of 47.87%, the specificity of 89.21%, positive predictive value of 89.76%, and the negative predictive value of 46.53% for predicting coronary artery stenosis. After treatment, the blood pressure levels of the patients, both systolic (SBP) and diastolic blood pressure (DBP) levels significantly decreased compared to before treatment. Conclusion: A significant positive correlation was observed between the severity of coronary artery lesions and retinal artery lesions. Assessing alterations in retinal blood vessels in hypertensive patients can effectively indicate the extent of coronary artery stenosis indirectly. Concerning medication, the antihypertensive drug captopril demonstrated the potential to alleviate the severity of coronary artery and retinal artery lesions in hypertensive patients. However, specific treatment methods should be tailored to individual patient circumstances.

17.
Nano Lett ; 23(8): 3385-3393, 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37052258

RESUMO

Lead halide perovskite nanocrystals (LHP NCs) are regarded as promising emitters for next-generation ultrahigh-definition displays due to their high color purity and wide color gamut. Recently, the external quantum efficiency (EQE) of LHP NC based light-emitting diodes (PNC LEDs) has been rapidly improved to a level required by practical applications. However, the poor operational stability of the device, caused by halide ion migration at the grain boundary of LHP NC thin films, remains a great challenge. Herein, we report a resurfacing strategy via pseudohalogen ions to mitigate detrimental halide ion migration, aiming to stabilize PNC LEDs. We employ a thiocyanate solution processed post-treatment method to efficiently resurface CsPbBr3 NCs and demonstrate that the thiocyanate ions can effectively inhibit bromide ion migration in LHP NC thin films. Owing to thiocyanate resurfacing, we fabricated LEDs with a high EQE of 17.3%, a maximum brightness of 48000 cd m-2, and an excellent operation half-life time.

18.
J Environ Sci (China) ; 144: 76-86, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38802240

RESUMO

In this study, high temperature thermotolerant nitrifying bacteria (TNB) and high temperature thermotolerant sulfide oxidizing bacteria (TSOB) were obtained from compost samples and inoculated into sewage sludge (SS) compost. The effects of inoculation on physical and chemical parameters, ammonia and hydrogen sulfide release, nitrogen form and sulfur compound content change and physical-chemical properties during nitrogen and sulfur conversion were studied. The results showed that inoculation of TNB and TSOB increased the temperature, pH, OM degradation, C/N ratio and germination index (GI) of compost. Compared with the control treatment (CK), the addition of inoculants reduced the release of NH3 and H2S, and transformed them into nitrogen and sulfur compounds, the hydrolysis of polymeric ferrous sulfate was promoted, resulting in relatively high content of sulfite and sulfate. At the same time, the physical and chemical properties of SS have a strong correlation with nitrogen and sulfur compounds.


Assuntos
Compostagem , Nitrificação , Nitrogênio , Esgotos , Enxofre , Esgotos/microbiologia , Nitrogênio/metabolismo , Enxofre/metabolismo , Compostagem/métodos , Oxirredução , Eliminação de Resíduos Líquidos/métodos , Bactérias/metabolismo
19.
Angew Chem Int Ed Engl ; 63(29): e202404978, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38697945

RESUMO

Integrating aggregation-induced emission (AIE) into thermally activated delayed fluorescence (TADF) emitters holds great promise for the advancement of highly efficient organic light emitting diodes (OLEDs). Despite recent advancements, a thorough comprehension of the underlying mechanisms remains imperative for the practical application of such materials. In this work, we introduce a novel approach aimed at modulating the TADF process by manipulating dynamic processes in excited states through aggregation effect. Our findings reveal that aggregation not only enhances both prompt and delayed fluorescence simultaneously but also imposes constraints on molecular reorientation. This constraint reinforces spin-orbit coupling and reduces the energy gap between singlets and triplets. These insights deepen our understanding of the fundamental mechanisms governing the aggregation effect on TADF materials and provide valuable guidance for the design of high-efficiency photoluminescent materials.

20.
Anal Chem ; 95(4): 2504-2512, 2023 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-36651128

RESUMO

The establishment and application of a generalizable three-dimensional (3D) tumor device for high-throughput screening plays an important role in drug discovery and cancer therapeutics. In this study, we introduce a facile microplatform for considerable 3D tumor generation and combinatorial drug screening evaluation. High fidelity of chip fabrication was achieved depending on the simple and well-improved microcontact printing. We demonstrated the high stability and repeatability of the established tumor-on-a-chip system for controllable and massive production of 3D tumors with high size uniformity. Importantly, we accomplished the screening-like chemotherapy investigation involving individual and combinatorial drugs and validated the high accessibility and applicability of the system in 3D tumor-based manipulation and analysis on a large scale. This achievement in tumor-on-a-chip has potential applications in plenty of biomedical fields such as tumor biology, pharmacology, and tissue microengineering. It offers an insight into the development of the popularized microplatform with easy-to-fabricate and easy-to-operate properties for cancer exploration and therapy.


Assuntos
Neoplasias , Humanos , Avaliação Pré-Clínica de Medicamentos/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Ensaios de Triagem em Larga Escala , Descoberta de Drogas , Impressão Tridimensional
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