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1.
Front Neurosci ; 18: 1181670, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38737099

RESUMO

Given its high morbidity, disability, and mortality rates, ischemic stroke (IS) is a severe disease posing a substantial public health threat. Although early thrombolytic therapy is effective in IS treatment, the limited time frame for its administration presents a formidable challenge. Upon occurrence, IS triggers an ischemic cascade response, inducing the brain to generate endogenous protective mechanisms against excitotoxicity and inflammation, among other pathological processes. Stroke patients often experience limited recovery stages. As a result, activating their innate self-protective capacity [endogenous brain protection (EBP)] is essential for neurological function recovery. Acupuncture has exhibited clinical efficacy in cerebral ischemic stroke (CIS) treatment by promoting the human body's self-preservation and "Zheng Qi" (a term in traditional Chinese medicine (TCM) describing positive capabilities such as self-immunity, self-recovery, and disease prevention). According to research, acupuncture can modulate astrocyte activity, decrease oxidative stress (OS), and protect neurons by inhibiting excitotoxicity, inflammation, and apoptosis via activating endogenous protective mechanisms within the brain. Furthermore, acupuncture was found to modulate microglia transformation, thereby reducing inflammation and autoimmune responses, as well as promoting blood flow restoration by regulating the vasculature or the blood-brain barrier (BBB). However, the precise mechanism underlying these processes remains unclear. Consequently, this review aims to shed light on the potential acupuncture-induced endogenous neuroprotective mechanisms by critically examining experimental evidence on the preventive and therapeutic effects exerted by acupuncture on CIS. This review offers a theoretical foundation for acupuncture-based stroke treatment.

2.
BMC Cancer ; 24(1): 549, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38693523

RESUMO

BACKGROUND: Accurate assessment of axillary status after neoadjuvant therapy for breast cancer patients with axillary lymph node metastasis is important for the selection of appropriate subsequent axillary treatment decisions. Our objectives were to accurately predict whether the breast cancer patients with axillary lymph node metastases could achieve axillary pathological complete response (pCR). METHODS: We collected imaging data to extract longitudinal CT image features before and after neoadjuvant chemotherapy (NAC), analyzed the correlation between radiomics and clinicopathological features, and developed models to predict whether patients with axillary lymph node metastasis can achieve axillary pCR after NAC. The clinical utility of the models was determined via decision curve analysis (DCA). Subgroup analyses were also performed. Then, a nomogram was developed based on the model with the best predictive efficiency and clinical utility and was validated using the calibration plots. RESULTS: A total of 549 breast cancer patients with metastasized axillary lymph nodes were enrolled in this study. 42 independent radiomics features were selected from LASSO regression to construct a logistic regression model with clinicopathological features (LR radiomics-clinical combined model). The AUC of the LR radiomics-clinical combined model prediction performance was 0.861 in the training set and 0.891 in the testing set. For the HR + /HER2 - , HER2 + , and Triple negative subtype, the LR radiomics-clinical combined model yields the best prediction AUCs of 0.756, 0.812, and 0.928 in training sets, and AUCs of 0.757, 0.777 and 0.838 in testing sets, respectively. CONCLUSIONS: The combination of radiomics features and clinicopathological characteristics can effectively predict axillary pCR status in NAC breast cancer patients.


Assuntos
Axila , Neoplasias da Mama , Linfonodos , Metástase Linfática , Terapia Neoadjuvante , Nomogramas , Tomografia Computadorizada por Raios X , Humanos , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Metástase Linfática/diagnóstico por imagem , Pessoa de Meia-Idade , Linfonodos/patologia , Linfonodos/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Terapia Neoadjuvante/métodos , Adulto , Idoso , Estudos Retrospectivos , Radiômica
3.
Nat Commun ; 15(1): 2995, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38582773

RESUMO

Improving the kinetics and selectivity of CO2/CO electroreduction to valuable multi-carbon products is a challenge for science and is a requirement for practical relevance. Here we develop a thiol-modified surface ligand strategy that promotes electrochemical CO-to-acetate. We explore a picture wherein nucleophilic interaction between the lone pairs of sulfur and the empty orbitals of reaction intermediates contributes to making the acetate pathway more energetically accessible. Density functional theory calculations and Raman spectroscopy suggest a mechanism where the nucleophilic interaction increases the sp2 hybridization of CO(ad), facilitating the rate-determining step, CO* to (CHO)*. We find that the ligands stabilize the (HOOC-CH2)* intermediate, a key intermediate in the acetate pathway. In-situ Raman spectroscopy shows shifts in C-O, Cu-C, and C-S vibrational frequencies that agree with a picture of surface ligand-intermediate interactions. A Faradaic efficiency of 70% is obtained on optimized thiol-capped Cu catalysts, with onset potentials 100 mV lower than in the case of reference Cu catalysts.

4.
Orthop Surg ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658320

RESUMO

OBJECTIVE: Bone marrow mesenchymal stem cells (BMSCs) show significant potential for osteogenic differentiation. However, the underlying mechanisms of osteogenic capability in osteoporosis-derived BMSCs (OP-BMSCs) remain unclear. This study aims to explore the impact of YTHDF3 (YTH N6-methyladenosine RNA binding protein 3) on the osteogenic traits of OP-BMSCs and identify potential therapeutic targets to boost their bone formation ability. METHODS: We examined microarray datasets (GSE35956 and GSE35958) from the Gene Expression Omnibus (GEO) to identify potential m6A regulators in osteoporosis (OP). Employing differential, protein interaction, and machine learning analyses, we pinpointed critical hub genes linked to OP. We further probed the relationship between these genes and OP using single-cell analysis, immune infiltration assessment, and Mendelian randomization. Our in vivo and in vitro experiments validated the expression and functionality of the key hub gene. RESULTS: Differential analysis revealed seven key hub genes related to OP, with YTHDF3 as a central player, supported by protein interaction analysis and machine learning methodologies. Subsequent single-cell, immune infiltration, and Mendelian randomization studies consistently validated YTHDF3's significant link to osteoporosis. YTHDF3 levels are significantly reduced in femoral head tissue from postmenopausal osteoporosis (PMOP) patients and femoral bone tissue from PMOP mice. Additionally, silencing YTHDF3 in OP-BMSCs substantially impedes their proliferation and differentiation. CONCLUSION: YTHDF3 may be implicated in the pathogenesis of OP by regulating the proliferation and osteogenic differentiation of OP-BMSCs.

5.
Knee Surg Sports Traumatol Arthrosc ; 32(5): 1113-1122, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38469920

RESUMO

PURPOSE: This study aimed to assess the relationship between the geometric features of tibial eminence and susceptibility to noncontact anterior cruciate ligament (ACL) injuries. METHODS: Patients with unilateral noncontact knee injuries between 2015 and 2021 were consecutively enroled in this study. Based on knee magnetic resonance imaging (MRI) and arthroscopic visualisation, patients were categorised into the case group (ACL rupture) and control group (ACL intact). Using MRI, the geometric features of tibial eminence were characterised by measuring the sagittal slopes, depth of concavity and coronal slopes of the inclined surfaces of the tibial spines. Univariate and multivariate logistic regressions were conducted to explore independent associations between quantified geometric indices of tibial eminence and the risk of noncontact ACL injuries. RESULTS: This study included 187 cases and 199 controls. A decreased sagittal slope of the medial tibial spine (MTSSS) (combined group: odds ratio [OR]: 0.87 [0.82, 0.92], p < 0.001; females: OR: 0.88 [0.80, 0.98], p = 0.020; males: OR: 0.87 [0.81, 0.93], p < 0.001) and an increased depth of concavity in the lateral tibial spine (LTSD) (combined group: OR: 1.51 [1.24, 1.85], p < 0.001; females: OR: 1.65 [1.12, 2.43], p = 0.012; males: OR: 1.44 [1.11, 1.89], p = 0.007) were independent risk factors for noncontact ACL injuries. Moreover, a steeper coronal slope of the inclined surface of the medial tibial spine was a significant predictor of noncontact ACL injuries for males (MTSCS: OR: 1.04 [1.01, 1.08], p = 0.015) but not for females. CONCLUSION: Geometric features of tibial eminence, particularly a decreased MTSSS and an increased LTSD, were identified as independent risk factors for noncontact ACL injuries. These findings will help clinicians identify individuals at high risk of ACL injury and facilitate the development of targeted prevention strategies. LEVEL OF EVIDENCE: Level III.


Assuntos
Lesões do Ligamento Cruzado Anterior , Imageamento por Ressonância Magnética , Tíbia , Humanos , Feminino , Masculino , Fatores de Risco , Tíbia/diagnóstico por imagem , Adulto , Adulto Jovem , Estudos de Casos e Controles , Artroscopia , Adolescente
6.
J Am Chem Soc ; 146(12): 8641-8649, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38470826

RESUMO

Renewable-energy-powered electrosynthesis has the potential to contribute to decarbonizing the production of propylene glycol, a chemical that is used currently in the manufacture of polyesters and antifreeze and has a high carbon intensity. Unfortunately, to date, the electrooxidation of propylene under ambient conditions has suffered from a wide product distribution, leading to a low faradic efficiency toward the desired propylene glycol. We undertook mechanistic investigations and found that the reconstruction of Pd to PdO occurs, followed by hydroxide formation under anodic bias. The formation of this metastable hydroxide layer arrests the progressive dissolution of Pd in a locally acidic environment, increases the activity, and steers the reaction pathway toward propylene glycol. Rh-doped Pd further improves propylene glycol selectivity. Density functional theory (DFT) suggests that the Rh dopant lowers the energy associated with the production of the final intermediate in propylene glycol formation and renders the desorption step spontaneous, a concept consistent with experimental studies. We report a 75% faradic efficiency toward propylene glycol maintained over 100 h of operation.

7.
Environ Toxicol ; 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38400521

RESUMO

Lung cancer is one of the most common malignant tumors in the world. In approximately 30%-40% of lung cancer patients, bone metastases ensues with osteolytic destruction. Worse still, intractable pain, pathological fracture, and nerve compression caused by bone metastases are currently the bottleneck of research, diagnosis, and treatment of lung cancer. Therefore, the present study aims at investigating the effectiveness of a new composite material made of calcium phosphate cement (CPC) and Endostar on repairing bone defects in vitro and in vivo. As indicated in results, the mechanical properties of CPC+Endostar and CPC+PLGA+Endostar do not differ from those of pure CPC. The PLGA-embedded Endostar slow-release microspheres were designed and prepared, and were combined with CPC. Poly (lactic-co-glycolic acid (PLGA) is a biodegradable polymer material in vivo, so the effect on its mechanical properties is negligible. CPC+Endostar and CPC+PLGA+Endostar have been proved to inhibit cell proliferation, promote apoptosis and block cell cycle in G2 phase; the expression levels of osteoclast-related genes CXCL2, TGF-ß1, IGF-1, IL-6, and RANKL were significantly decreased while osteogenic ability and alkaline phosphatase activity observably enhanced. In vivo studies have revealed that the expression levels of TRAP, RANKL, and Caspase3 in CPC+PLGA+ENDO-treated tumor tissues after 3 weeks were higher than those in other groups with the prolongation of animal treatment time, while the expression levels of OPN and BCL2 were lower than those in other groups. In hematoxylin and eosin and TUNEL staining, 3 weeks of CPC+PLGA+ENDO-treatment yielded higher tissue necrosis and apoptosis than other groups; computed tomography and magnetic resonance imaging results showed the posterior edge bone damage reduced as a result of the CPC+PLGA+ENDO grafting in vertebral pedicle. Overall, the feasibility and reliability of CPC-loaded Endostar in the treatment of bone metastasis in lung cancer were investigated in this study, so as to promote the basic research and treatment of bone metastasis in lung cancer and other malignant tumors.

8.
Adv Mater ; : e2312778, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38421936

RESUMO

Hydrogenation of biomass-derived chemicals is of interest for the production of biofuels and valorized chemicals. Thermochemical processes for biomass reduction typically employ hydrogen as the reductant at elevated temperatures and pressures. Here, the authors investigate the direct electrified reduction of 5-hydroxymethylfurfural (HMF) to a precursor to bio-polymers, 2,5-bis(hydroxymethyl)furan (BHMF). Noting a limited current density in prior reports of this transformation, a hybrid catalyst consisting of ternary metal nanodendrites mixed with a cationic ionomer, the latter purposed to increase local pH and facilitate surface proton diffusion, is investigated. This approach, when implemented using Ga-doped Ag-Cu electrocatalysts designed for p-d orbital hybridization, steered selectivity to BHMF, achieving a faradaic efficiency (FE) of 58% at 100 mA cm-2 and a production rate of 1 mmol cm-2 h-1, the latter a doubling in rate compared to the best prior reports.

9.
Zhen Ci Yan Jiu ; 49(1): 71-78, 2024 Jan 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38239141

RESUMO

Acupuncture has a positive effect in the treatment of ischemic stroke (IS). A number of studies have confirmed that the role of acupuncture in the treatment of IS, which is closely related to its functions of regulating mitochondrial functions. In the present article, we review the mechanisms of acupuncture underlying improvement of mitochondria in the treatment of IS from 4 aspects: 1) protecting mitochondrial structure integrity, 2) regulative effect on mitochondrial functional activities, including regulating energy metabolism, reducing oxidative stress, suppressing calcium overload, and regulating mitochondrial membrane potential changes, 3) regulating mitochondrial quality control system, including promoting mitochondrial biosynthesis, regulating mitochondrial dynamics and apoptosis, and 4) regula-ting mitochondria-related apoptosis pathways. All of these may provide a theoretical basis for acupuncture in the treatment of IS and a reference for further research.


Assuntos
Terapia por Acupuntura , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/metabolismo , Mitocôndrias/genética , Mitocôndrias/metabolismo , Neurônios/metabolismo , Estresse Oxidativo , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/terapia
10.
Biomedicines ; 12(1)2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38255219

RESUMO

BACKGROUND: The pivotal roles of long noncoding RNAs (lncRNAs) in the realm of cancer biology, inclusive of bladder cancer (BCa), have been substantiated through various studies. Remarkably, RNA methylation, especially m6A modification, has demonstrated its influence on both coding and noncoding RNAs. Nonetheless, the explicit impact of RNA methylation on lncRNAs and its subsequent contribution to the progression of BCa remains to be elucidated. METHODS: In the present investigation, we scrutinized the expression and m6A methylation status of LINC01106, employing quantitative real-time PCR (qRT-PCR) and methylated RNA immunoprecipitation (MeRIP)-qPCR. To decipher the regulatory mechanism underpinning LINC01106, we utilized RNA immunoprecipitation (RIP)-qPCR, methylated RNA immunoprecipitation (MeRIP) assays, and bioinformatic analysis. Furthermore, the CRISPR/dCas13b-METTL3-METTL14 system was implemented to probe the function of LINC01106. RESULTS: The findings of our study indicated that LINC01106 is under expressed and exhibits diminished m6A methylation levels in BCa tissues when compared those of normal controls. A diminished expression of LINC01106 was associated with a less favorable prognosis in BCa patients. Intriguingly, CRISPR-mediated hypermethylation of LINC01106, facilitated by dCas13b-M3-M14, abolished the malignant phenotype of the BCa cells, an effect that could be inverted by Disabled-1 (DAB1) knockdown. From a mechanistic standpoint, we identified an m6A modification site on LINC01106 and highlighted YTHDC1 as a potential reader protein implicated in this process. Additionally, a positive correlation between DAB1 and LINC01106 expression was observed, with miR-3148 potentially acting as a mediator in this relationship. CONCLUSIONS: In summary, our research unveils a suppressive regulatory role of the LINC01106/miR-3148/DAB1 axis in the progression of BCa and underscores the YTHDC1-mediated m6A modification mechanism in regards to LINC01106. These revelations propose a new therapeutic target for the management of BCa.

11.
Clin Nutr ; 43(1): 211-217, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38086258

RESUMO

PURPOSE: Current evidence on the association of serum vitamin D with mortality in postmenopausal women is limited and inconsistent. Therefore, the purpose of this study was to examine the relationship between serum vitamin D and mortality in postmenopausal women. METHODS: In this study, we used data from the NHANES (2001-2018) and conducted a multivariate Cox regression model to examine associations between serum vitamin D and all-cause mortality, cardiovascular mortality (CVD), and cancer mortality. RESULTS: In a median follow-up period of 8.3 years, 1905 deaths of all causes were reported, 601 were due to CVD, and 385 deaths were due to cancer. After multivariable adjustment, higher serum vitamin D levels were significantly associated with a reduced risk of death. Compared to participants with lower vitamin D levels (<25 nmol/L), those with higher vitamin D levels (≥75.0 nmol/L) had a lower risk of all-cause mortality (hazard ratio 0.60, 95 % confidence interval 0.49 to 0.74), a lower risk of cardiovascular mortality (0.51, 0.35 to 0.74), and a lower risk of cancer mortality (0.43, 0.28 to 0.67). Moreover, we observed an L-shaped dose-response relationship of serum vitamin D levels with all-cause mortality, and cancer mortality, with this inflexion point being 55.9 nmol/L, and 51.2 nmol/L, respectively. CONCLUSIONS: Higher concentrations of serum vitamin D substantially correlated with a reduction in mortality risk from all-cause, CVD, and cancer in postmenopausal women. These results imply that upholding adequate vitamin D levels may help prevent premature death in postmenopausal women.


Assuntos
Doenças Cardiovasculares , Neoplasias , Deficiência de Vitamina D , Humanos , Feminino , Vitamina D , Pós-Menopausa , Inquéritos Nutricionais , Vitaminas , Neoplasias/complicações
12.
Nat Nanotechnol ; 19(3): 311-318, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37996517

RESUMO

The electrochemical reduction of CO2 in acidic conditions enables high single-pass carbon efficiency. However, the competing hydrogen evolution reaction reduces selectivity in the electrochemical reduction of CO2, a reaction in which the formation of CO, and its ensuing coupling, are each essential to achieving multicarbon (C2+) product formation. These two reactions rely on distinct catalyst properties that are difficult to achieve in a single catalyst. Here we report decoupling the CO2-to-C2+ reaction into two steps, CO2-to-CO and CO-to-C2+, by deploying two distinct catalyst layers operating in tandem to achieve the desired transformation. The first catalyst, atomically dispersed cobalt phthalocyanine, reduces CO2 to CO with high selectivity. This process increases local CO availability to enhance the C-C coupling step implemented on the second catalyst layer, which is a Cu nanocatalyst with a Cu-ionomer interface. The optimized tandem electrodes achieve 61% C2H4 Faradaic efficiency and 82% C2+ Faradaic efficiency at 800 mA cm-2 at 25 °C. When optimized for single-pass utilization, the system reaches a single-pass carbon efficiency of 90 ± 3%, simultaneous with 55 ± 3% C2H4 Faradaic efficiency and a total C2+ Faradaic efficiency of 76 ± 2%, at 800 mA cm-2 with a CO2 flow rate of 2 ml min-1.

13.
ACS Omega ; 8(47): 44485-44496, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38046301

RESUMO

Steam huff-n-puff in horizontal wells often had limitations, such as uneven steam injection and low reservoir utilization. To improve steam injection efficiency, a new method for designing a supersonic nozzle was proposed based on the principles of aerodynamics and thermodynamics. The nozzle featured a tapering section, a throat, and a diverging section. The best geometric shape of the tapering section was the Witoszynski curve. A set of nozzle size designs were established, and the size parameters were optimized. The results showed that the nozzle could inject steam into the formation at supersonic speed and it had the characteristics of constant flow rate and uniform development of the steam chamber. According to the steam Reynolds number and the good aggregation distribution characteristics of the size design model, three sequential nozzles of 3.0, 5.0, and 6.5 mm were formed based on the throat. When the throat diameter was 5.0 mm, the tapering length was 4.3 mm, the diverging length was 5.5 mm, the throat length was 3.0 mm, the inlet diameter was 9.8 mm, and the outlet diameter was 6.2 mm. Numerical simulations indicated that the pressure drop loss during steam huff-n-puff injection in horizontal wells was within 10%. It was of great significance to establish the nozzle size design model of the steam injection effect of horizontal wells.

14.
Eur J Med Res ; 28(1): 589, 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38093387

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most prevalent forms of cancer and poses a threat to the health and survival of humans. Mitochondrial ribosomal protein L48 (MRPL48) belongs to the mitochondrial ribosomal protein family, which participates in energy production. Studies have shown that MRPL48 can predict osteosarcoma incidence and prognosis, as well as promotes colorectal cancer progression. However, the role of MRPL48 in HCC remains unknown. METHODS: TCGA, GEO, HCCDB, CPTAC, SMART, UALCAN, Kaplan-Meier plotter, cBioPortal, and MethSurv were performed for bioinformatics purposes. Quantitative RT-PCR, immunoblotting, and functional studies were conducted to validate the methodology in vitro. RESULTS: MRPL48 was greatly overexpressed in HCC tissues, compared with healthy tissue, which was subsequently demonstrated in vitro as well. The survival and regression analyses showed that MRPL48 expression is of significant clinical prognostic value in HCC. The ROC curve and nomogram analysis indicated that MRPL48 is a powerful predictor of HCC. MRPL48 methylation was adversely associated with the expression of MRPL48, and patients with a low level of methylation had poorer overall survival than those with a high level of methylation. GSEA showed that the expression of the MRPL48 was correlated with Resolution of Sister Chromatid Cohesion, Mitotic Prometaphase, Retinoblastoma Gene in Cancer, RHO Gtpases Activate Formins, Mitotic Metaphase and Anaphase, and Cell Cycle Checkpoints. An analysis of immune cell infiltration showed a significant association between MRPL48 and immune cell infiltration subsets, which impacted the survival of HCC patients. Additionally, MRPL48 knockdown reduced HCC cell proliferation, migration, and invasion in vitro. CONCLUSIONS: We demonstrated that MRPL48 expression may be associated with HCC development and prognosis. These findings may open up new research directions and opportunities for the development of HCC treatments.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Prognóstico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Biomarcadores , Proteínas Ribossômicas
15.
World J Gastrointest Surg ; 15(11): 2639-2645, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38111759

RESUMO

BACKGROUND: Isolated gallbladder injury (GI) (IGI) directly induced by abdominal trauma is rare. Symptoms, indications, and imaging examinations of IGI are frequently non-specific, posing tremendous diagnostic challenges, which are simple to overlook and may have severe implications. Improving doctors' understanding of gallbladder injury (GI) facilitates early detection and decreases the likelihood of severe consequences, including death. CASE SUMMARY: We report a case of IGI caused by blunt violence (after falling from three meters with the umbilicus as the stress point) and performed laparoscopic repair of the gallbladder rupture, which helps clinicians understand IGI and reduce the severe consequences of delayed diagnosis. Through extensive medical history and dynamic abdominal ultrasound evaluation, doctors can identify GI early and begin surgery, thereby decreasing the devastating repercussions of delayed diagnosis. CONCLUSION: This article aims to improve clinicians' understanding of IGI and propose a method for the diagnosis and treatment of GI.

16.
Sci Rep ; 13(1): 17134, 2023 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-37816883

RESUMO

Psoriasis, which is one of the most common skin diseases, involves an array of complex immune constituents including T cells, dendritic cells and monocytes. Particularly, the cytokine IL17A, primarily generated by TH17 cells, assumes a crucial function in the etiology of psoriasis. In this study, a comprehensive investigation utilizing bulk RNA analysis, single-cell RNA sequencing, and spatial transcriptomics was employed to elucidate the underlying mechanisms of psoriasis. Our study revealed that there is an overlap between the genes that are differentially expressed in psoriasis patients receiving three anti-IL17A monoclonal antibody drugs and the genes that are differentially expressed in lesion versus non-lesion samples in these patients. Further analysis using single-cell and spatial data from psoriasis samples confirmed the expression of hub genes that had low expressions in psoriasis tissue but were up-regulated after anti-IL17A treatments. These genes were found to be associated with the treatment effects of brodalumab and methotrexate, but not adalimumab, etanercept, and ustekinumab. Additionally, these genes were predominantly expressed in fibroblasts. In our study, fibroblasts were categorized into five clusters. Notably, hub genes exhibited predominant expression in cluster 3 fibroblasts, which were primarily engaged in the regulation of the extracellular matrix and were predominantly located in the reticular dermis. Subsequent analysis unveiled that cluster 3 fibroblasts also established communication with epithelial cells and monocytes via the ANGPTL-SDC4 ligand-receptor configuration, and their regulation was governed by the transcription factor TWIST1. Conversely, cluster 4 fibroblasts, responsible for vascular endothelial regulation, were predominantly distributed in the papillary dermis. Cluster 4 predominantly engaged in interactions with endothelial cells via MDK signals and was governed by the distinctive transcription factor, ERG. By means of an integrated analysis encompassing bulk transcriptomics, single-cell RNA sequencing, and spatial transcriptomics, we have discerned genes and clusters of fibroblasts that potentially contribute to the pathogenesis of psoriasis.


Assuntos
Psoríase , Transcriptoma , Humanos , Células Endoteliais/metabolismo , Psoríase/metabolismo , Fatores de Transcrição/genética , Fibroblastos/metabolismo
17.
Osteoporos Int ; 34(12): 2101-2110, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37666910

RESUMO

This cross-sectional study investigated the relationship between composite dietary antioxidant index (CDAI) and individual dietary antioxidant intakes, including vitamins A, C, and E, zinc, selenium, and carotenoids, and bone mineral density (BMD) in the US population aged 20 years older. We found a positive correlation between CDAI and femoral BMD. Moreover, higher intakes of vitamin C, vitamin E, selenium, zinc, and carotenoids were associated with higher femoral BMD. INTRODUCTION: While individual dietary antioxidants have shown beneficial effects on bone metabolism, the diverse and potentially interacting nature of dietary components may limit the accuracy of evaluating their impact on bone health. Thus, this study aims to investigate the association between CDAI and BMD. Additionally, we explore the relationship between the intake of individual components of the CDAI and BMD. METHODS: The CDAI is a novel index evaluating total dietary antioxidant intake, considering vitamins A, C, and E, zinc, selenium, and carotenoids. A cross-sectional analysis was conducted using data from participants aged ≥ 20 in the National Health and Nutrition Examination Survey (2005-2010, 2013-2014, and 2017-2018). We utilized multivariate linear regression models to examine the relationship between CDAI, individual dietary antioxidants, including vitamins A, C, and E, zinc, selenium, carotenoids, and femoral BMD. RESULTS: The final analysis included 10,584 participants with a mean age of 50.73 ± 16.65 years. After multivariate adjustment, the second to fourth quartiles of CDAI (- 2.00-0.04, 0.04-2.54, and 2.54-70.78) exhibited higher femoral BMD compared to the first quartile of CADI (- 7.34 to - 2.00). Multiple regression analysis revealed that higher intakes of vitamin C, vitamin E, selenium, zinc, and carotenoids were associated with higher femoral BMD. CONCLUSIONS: CDAI serves as a comprehensive tool for evaluating the overall antioxidant capacity of antioxidants in diets. Additionally, our study shows a positive correlation between CDAI and BMD, which indicates that the combined intake of dietary antioxidants may help reduce the risk of osteoporosis in adults.


Assuntos
Antioxidantes , Selênio , Adulto , Humanos , Pessoa de Meia-Idade , Idoso , Densidade Óssea , Inquéritos Nutricionais , Estudos Transversais , Vitaminas , Ácido Ascórbico , Dieta , Vitamina E , Vitamina A , Carotenoides , Zinco
18.
Angew Chem Int Ed Engl ; 62(42): e202310970, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37644643

RESUMO

The large-scale applicability of Zn-metal anodes is severely impeded by the issues such as the dendrite growth, complicated hydrogen evolution, and uncontrollable passivation reaction. Herein, a negatively charged carboxylated double-network hydrogel electrolyte (Gelatin/Sodium alginate-acetate, denoted as Gel/SA-acetate) has been developed to stabilize the interfacial electrochemistry, which restructures a type of Zn2+ ion solvent sheath optimized via a chain-liquid synergistic effect. New hydrogen bonds are reconstructed with water molecules by the zincophilic functional groups, and directional migration of hydrated Zn2+ ions is therefore induced. Concomitantly, the robust chemical bonding of such hydrogel layers to the Zn slab exhibits a desirable anti-catalytic effect, thereby greatly diminishing the water activity and eliminating side reactions. Subsequently, a symmetric cell using the Gel/SA-acetate electrolyte demonstrates a reversible plating/stripping performance for 1580 h, and an asymmetric cell reaches a state-of-the-art runtime of 5600 h with a high average Coulombic efficiency of 99.9 %. The resultant zinc ion hybrid capacitors deliver exceptional properties including the capacity retention of 98.5 % over 15000 cycles, energy density of 236.8 Wh kg-1 , and high mechanical adaptability. This work is expected to pave a new avenue for the development of novel hydrogel electrolytes towards safe and stable Zn anodes.

19.
Small ; 19(45): e2302629, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37431237

RESUMO

Tailor-made carbonaceous-based cathodes with zincophilicity and hydrophilicity are highly desirable for Zn-ion storage applications, but it remains a great challenge to achieve both advantages in the synthesis. In this work, a template electrospinning strategy is developed to synthesize nitrogen and phosphorous co-doped hollow porous carbon nanofibers (N, P-HPCNFs), which deliver a high capacity of 230.7 mAh g-1 at 0.2 A g-1 , superior rate capability of 131.0 mAh g-1 at 20 A g-1 , and a maximum energy density of 196.10 Wh kg-1 at the power density of 155.53 W kg-1 . Density functional theory calculations (DFT) reveal that the introduced P dopants regulate the distribution of local charge density of carbon materials and therefore facilitate the adsorption of Zn ions due to the increased electronegativity of pyridinic-N. Ab initio molecular dynamics (AIMD) simulations indicate that the doped P species induce a series of polar sites and create a hydrophilic microenvironment, which decreases the impedance between the electrode and the electrolyte and therefore accelerates the reaction kinetics. The marriage of ex situ/in situ experimental analyses and theoretical simulations uncovers the origin of the enhanced zincophilicity and hydrophilicity of N, P-HPCNFs for energy storage, which accounts for the faster ion migration and electrochemical processes.

20.
Endocrine ; 82(1): 190-200, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37450217

RESUMO

PURPOSE: This study aimed to develop and validate a simple primary osteoporosis screening tool (POST) based on adults aged 50 years and older. METHODS: This study included participants aged ≥50 from the National Health and Nutrition Examination Survey. Osteoporosis was defined according to bone mineral density values. The POST was developed based on methods from previous studies. Moreover, we plotted the receiver operating characteristic curves to calculate the area under the curve (AUC) and determine the optimal cut-off value according to the weighted Youden index. In addition, we compared the performances in identifying individuals with osteoporosis between the POST and the Osteoporosis Self-assessment Tool (OST). Finally, we also assessed the performance of the POST in the Chinese population. RESULTS: Finally, a total of 6665 individuals were included in this study. The AUC values of the POST for identifying individuals with osteoporosis in the development cohort and the validation cohort were 0.81 (95% CI: 0.79-0.83) and 0.81 (95% CI: 0.77-0.84), respectively. Moreover, a POST-score ≥7 was determined as the threshold to identify individuals with osteoporosis, in which the sensitivity was greater than 90%. In addition, the POST showed significantly higher sensitivity than the OST. Finally, the POST showed an AUC of 0.75 (95% CI: 0.65-0.85) among 94 Chinese subjects aged ≥50 years old. CONCLUSIONS: POST is a convenient and effective tool for osteoporosis screening among adults aged 50 years and over, which might provide new methodological support for future osteoporosis screening.


Assuntos
Osteoporose , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Sensibilidade e Especificidade , Inquéritos Nutricionais , Absorciometria de Fóton , Osteoporose/diagnóstico , Osteoporose/epidemiologia , Densidade Óssea , Programas de Rastreamento/métodos , Curva ROC , Medição de Risco/métodos
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