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1.
ACS Biomater Sci Eng ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38860704

RESUMO

Resorption and atrophy of the alveolar bone, as two consequences of osteoporosis that remarkably complicate the orthodontic and prosthodontic treatments, contribute to the differentiated biological features and force-induced response of jaw bone marrow-derived mesenchymal stem cells (JBMSCs) in elderly patients. We isolated and cultured JBMSCs from adolescent and adult patients and then simulated the loading of orthodontic tension stress by constructing an in vitro three-dimensional (3D) stress loading model. The decline in osteogenic differentiation of aged JBMSCs was reversed by tensile stress stimulation. It is interesting to note that tension stimulation had a stronger effect on the osteogenic differentiation of elderly JBMSCs compared to the young ones, indicating a possible mechanism of aging rescue. High-throughput sequencing of microRNA (miRNAs) was subsequently performed before and after tension stimulation in all JBMSCs, followed by the comprehensive comparison of mechanically responsive miRNAs in the 3D strain microenvironment. The results suggested a significant reduction in the expression of miR-210-3p and miR-214-3p triggered by the 3D strain microenvironment in old-JBMSCs. Bioinformatic analysis indicated that both miRNAs participate in the regulation of critical pathways of aging and cellular senescence. Taken together, this study demonstrated that the 3D strain microenvironment efficiently rescued the cellular senescence of old-JBMSCs via modulating specific miRNAs, which provides a novel strategy for coordinating periodontal bone loss and regeneration of the elderly.

2.
Acta Pharm Sin B ; 14(6): 2554-2566, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38828147

RESUMO

Oncolytic viruses (OVs), a group of replication-competent viruses that can selectively infect and kill cancer cells while leaving healthy cells intact, are emerging as promising living anticancer agents. Unlike traditional drugs composed of non-replicating compounds or biomolecules, the replicative nature of viruses confer unique pharmacokinetic properties that require further studies. Despite some pharmacokinetics studies of OVs, mechanistic insights into the connection between OV pharmacokinetics and antitumor efficacy remain vague. Here, we characterized the pharmacokinetic profile of oncolytic virus M1 (OVM) in immunocompetent mouse tumor models and identified the JAK‒STAT pathway as a key modulator of OVM pharmacokinetics. By suppressing the JAK‒STAT pathway, early OVM pharmacokinetics are ameliorated, leading to enhanced tumor-specific viral accumulation, increased AUC and Cmax, and improved antitumor efficacy. Rather than compromising antitumor immunity after JAK‒STAT inhibition, the improved pharmacokinetics of OVM promotes T cell recruitment and activation in the tumor microenvironment, providing an optimal opportunity for the therapeutic outcome of immune checkpoint blockade, such as anti-PD-L1. Taken together, this study advances our understanding of the pharmacokinetic-pharmacodynamic relationship in OV therapy.

3.
Biochem Pharmacol ; 225: 116327, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38823457

RESUMO

With the progressive aging of society, there is an increasing prevalence of age-related diseases that pose a threat to the elderly's quality of life. Adipose tissue, a vital energy reservoir with endocrine functions, is one of the most vulnerable tissues in aging, which in turn influences systematic aging process, including metabolic dysfunction. However, the underlying mechanism is still poorly understood. In this study, we found that NRG4, a novel adipokine, is obviously decreased in adipocyte tissues and serums during aging. Moreover, delivered recombinant NRG4 protein (rNRG4) into aged mice can ameliorate age-associated insulin resistance, glucose disorders and other metabolic disfunction. In addition, rNRG4 treatment alleviates age-associated hepatic steatosis and sarcopenia, accompanied with altered gene signatures. Together, these results indicate that NRG4 plays a key role in the aging process and is a therapeutic target for the treatment of age-associated metabolic dysfunction.


Assuntos
Adipócitos , Envelhecimento , Camundongos Endogâmicos C57BL , Neurregulinas , Animais , Camundongos , Neurregulinas/metabolismo , Neurregulinas/genética , Adipócitos/metabolismo , Adipócitos/efeitos dos fármacos , Envelhecimento/metabolismo , Masculino , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/metabolismo , Sarcopenia/metabolismo , Sarcopenia/prevenção & controle , Resistência à Insulina/fisiologia
4.
J Agric Food Chem ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38855973

RESUMO

Chronic atrophic gastritis (CAG) is characterized by the loss of gastric glandular cells, which are replaced by the intestinal-type epithelium and fibrous tissue. Ginsenoside Rg1 (Rg1) is the prevalent ginsenoside in ginseng, with a variety of biological activities, and is usually added to functional foods. As a novel form of programmed cell death (PCD), pyroptosis has received substantial attention in recent years. Despite the numerous beneficial effects, the curative impact of Rg1 on CAG and whether its putative mechanism is partially via inhibiting pyroptosis still remain unknown. To address this gap, we conducted a study to explore the mechanisms underlying the potential anti-CAG effect of Rg1. We constructed a CAG rat model using a multifactor comprehensive method. A cellular model was developed by using 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) combined with Nigericin as a stimulus applied to GES-1 cells. After Rg1 intervention, the levels of inflammatory indicators in the gastric tissue/cell supernatant were reduced. Rg1 relieved oxidative stress via reducing the myeloperoxidase (MPO) and malonaldehyde (MDA) levels in the gastric tissue and increasing the level of superoxide dismutase (SOD). Additionally, Rg1 improved MNNG+Nigericin-induced pyroptosis in the morphology and plasma membrane of the cells. Further research supported novel evidence for Rg1 in the regulation of the NF-κB/NLRP3/GSDMD pathway and the resulting pyroptosis underlying its therapeutic effect. Moreover, by overexpression and knockout of GSDMD in GES-1 cells, our findings suggested that GSDMD might serve as the key target in the effect of Rg1 on suppressing pyroptosis. All of these offer a potential theoretical foundation for applying Rg1 in ameliorating CAG.

5.
Front Pharmacol ; 15: 1368244, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38873427

RESUMO

Objective: The purpose of this study is to investigate the drug safety of three Transthyretin (TTR) inhibitors in the real world using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: This study extracted reports received by the FAERS database from the first quarter of 2018 to the third quarter of 2023 for descriptive analysis and disproportionality analysis. Safety signal mining was conducted at the Preferred Term (PT) level and the System Organ Class (SOC) level using reporting odds ratio (ROR). The characteristics of the time-to-onset curves were analyzed using the Weibull Shape Parameter (WSP). The cumulative incidence of TTR inhibitors was evaluated using the Kaplan-Meier method. Subgroup analyses were conducted based on whether the reporter was a medical professional. Results: A total of 3,459 reports of adverse events (AEs) caused by TTR inhibitors as the primary suspect (PS) drug were extracted. The top three reported AEs for patisiran were fatigue, asthenia, and fall, with the most unexpectedly strong association being nonspecific reaction. The top three reported AEs for vutrisiran were fall, pain in extremity and malaise, with the most unexpectedly strong association being subdural haematoma. The top three reported AEs for inotersen were platelet count decreased, blood creatinine increased, and fatigue, with the most unexpectedly strong association being blood albumin decreased. Vitamin A decreased, arthralgia, and dyspnea were the same AEs mentioned in the drug labels of all three drugs, while malaise and asthenia were the same unexpected significant signals. This study offers evidence of the variability in the onset time characteristics of AEs associated with TTR inhibitors, as well as evidence of differences in adverse event reporting between medical professionals and non-medical professionals. Conclusion: In summary, we compared the similarities and differences in drug safety of three TTR inhibitors in the real world using the FAERS database. The results indicate that not only do these three drugs share common AEs, but they also exhibit differences in drug safety profiles. This study contributes to enhancing the understanding of medical professionals regarding the safety of TTR inhibitors.

6.
Dev Cell ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38776924

RESUMO

A significant variation in chromatin accessibility is an epigenetic feature of leukemia. The cause of this variation in leukemia, however, remains elusive. Here, we identify SMARCA5, a core ATPase of the imitation switch (ISWI) chromatin remodeling complex, as being responsible for aberrant chromatin accessibility in leukemia cells. We find that SMARCA5 is required to maintain aberrant chromatin accessibility for leukemogenesis and then promotes transcriptional activation of AKR1B1, an aldo/keto reductase, by recruiting transcription co-activator DDX5 and transcription factor SP1. Higher levels of AKR1B1 are associated with a poor prognosis in leukemia patients and promote leukemogenesis by reprogramming fructose metabolism. Moreover, pharmacological inhibition of AKR1B1 has been shown to have significant therapeutic effects in leukemia mice and leukemia patient cells. Thus, our findings link the aberrant chromatin state mediated by SMARCA5 to AKR1B1-mediated endogenous fructose metabolism reprogramming and shed light on the essential role of AKR1B1 in leukemogenesis, which may provide therapeutic strategies for leukemia.

7.
J Asian Nat Prod Res ; : 1-10, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38753580

RESUMO

Nine jatrophane diterpenoids were isolated from the whole plant Euphorbia helioscopia, including two new ones, helioscopnins A (1) and B (2). Comprehensive spectroscopic data analysis and ECD calculations elucidated their structures, including absolute configurations. All compounds were evaluated for bioactivity towards autophagic flux by flow cytometry using HM mCherry-GFP-LC3 cells. Compounds 1, 3, 4, 5, 8, and 9 significantly increased autophagic flux.

8.
Heliyon ; 10(10): e31088, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38803913

RESUMO

Background: The impact of capsular closure vs non-closure in hip arthroscopy for femoracetabular impingement (FAI) was assessed by a meta-analysis. Methods: With the most recent search update occurring in August 2022, relevant studies were found by searching the Pubmed and EMBASE databases. A collection of studies was made that conducted hip arthroscopy for FAI. Review Manager 5.3 was used to carry out the meta-analysis. The dichotomous and continuous factors were compared using the odds ratios (OR) and mean differences (MD). A fixed-effect or random-effect model was chosen, depending on the degree of heterogeneity (I2). Forest plots were used to assess the results. A significance level of P < 0.05 was applied to the statistical analysis. Results: Ultimately, 15 studies were incorporated into the meta-analysis. The surgery time was longer for the capsular closure group (CC group) compared to the non-closure (NC group) group. (P < 0.001, SMD = 8.59, 95%CI [7.40, 9.77], I2 = 32 %). Following hip arthroscopy, the CC group's mHHS was superior to that of the NC group (P = 0.001, MD = 2.05, 95%CI [0.83, 3.27], I2 = 42 %), HOS-ADL (P < 0.001, MD = 4.29, 95%CI [3.08, 5.50], I2 = 0 %). The capsular closure group had a reduced rate of postoperative complications (P = 0.001, OR = 0.21, 95%CI [0.08, 0.54], I2 = 0 %) and conversion to THA (P = 0.01, OR = 0.42, 95%CI [0.21, 0.83], I2 = 0 %) following hip arthroscopy than the non-closure group. The revision rate, VAS, and postoperative HOS-SSS did not significantly differ between these two groups (P>0.05). Conclusion: The current meta-analysis found that the closed group had a lower complication rate and considerably greater mHHS and HOS-ADL following surgery compared to the non-closed capsule group. Whether this is related to the continuous progress of biomechanical and clinical research techniques deserves our attention. Level of evidence: Level IV, systematic review of Level I through Level III studies.

9.
World J Stem Cells ; 16(5): 525-537, 2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38817335

RESUMO

BACKGROUND: Acute kidney injury (AKI) is a common clinical syndrome with high morbidity and mortality rates. The use of pluripotent stem cells holds great promise for the treatment of AKI. Urine-derived stem cells (USCs) are a novel and versatile cell source in cell-based therapy and regenerative medicine that provide advantages of a noninvasive, simple, and low-cost approach and are induced with high multidifferentiation potential. Whether these cells could serve as a potential stem cell source for the treatment of AKI has not been determined. AIM: To investigate whether USCs can serve as a potential stem cell source to improve renal function and histological structure after experimental AKI. METHODS: Stem cell markers with multidifferentiation potential were isolated from human amniotic fluid. AKI severe combined immune deficiency (SCID) mice models were induced by means of an intramuscular injection with glycerol. USCs isolated from human-voided urine were administered via tail veins. The functional changes in the kidney were assessed by the levels of blood urea nitrogen and serum creatinine. The histologic changes were evaluated by hematoxylin and eosin staining and transferase dUTP nick-end labeling staining. Meanwhile, we compared the regenerative potential of USCs with bone marrow-derived mesenchymal stem cells (MSCs). RESULTS: Treatment with USCs significantly alleviated histological destruction and functional decline. The renal function was rapidly restored after intravenous injection of 5 × 105 human USCs into SCID mice with glycerol-induced AKI compared with injection of saline. Results from secretion assays conducted in vitro demonstrated that both stem cell varieties released a wide array of cytokines and growth factors. This suggests that a mixture of various mediators closely interacts with their biochemical functions. Two types of stem cells showed enhanced tubular cell proliferation and decreased tubular cell apoptosis, although USC treatment was not more effective than MSC treatment. We found that USC therapy significantly improved renal function and histological damage, inhibited inflammation and apoptosis processes in the kidney, and promoted tubular epithelial proliferation. CONCLUSION: Our study demonstrated the potential of USCs for the treatment of AKI, representing a new clinical therapeutic strategy.

10.
J Agric Food Chem ; 72(23): 13186-13195, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38814711

RESUMO

Ketopantoate hydroxymethyltransferase (KPHMT) plays a pivotal role in d-pantothenic acid biosynthesis. Most KPHMTs are homodecamers with low thermal stability, posing challenges for protein engineering and limiting output enhancement. Previously, a high-enzyme activity KPHMT mutant (K25A/E189S) from Corynebacterium glutamicum was screened as mother strain (M0). Building upon this strain, our study focused on interface engineering modifications, employing a multifaceted approach including integrating folding-free energy calculation, B-factor analysis, and conserved site analysis. Preliminary screening led to the selection of five mutants in the interface─E106S, E98T, E98N, S247I, and S247D─showing improved thermal stability, culminating in the double-site mutant M8 (M0-E98N/S247D). M8 exhibited a T1/2 value of 288.79 min at 50 °C, showing a 3.29-fold increase compared to M0. Meanwhile, the Tm value of M8 was elevated from 53.2 to 59.6 °C. Investigations of structural and molecular dynamics simulations revealed alterations in surface electrostatic charge distribution and the formation of increased hydrogen bonds between subunits, contributing to enhanced thermal stability. This investigation corroborates the efficacy of interface engineering modifications in bolstering KPHMT stability while showing its potential for positively impacting industrial d-pantothenic acid synthesis.


Assuntos
Proteínas de Bactérias , Corynebacterium glutamicum , Estabilidade Enzimática , Engenharia de Proteínas , Corynebacterium glutamicum/enzimologia , Corynebacterium glutamicum/genética , Corynebacterium glutamicum/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Simulação de Dinâmica Molecular , Cinética , Temperatura Alta
11.
Neurorehabil Neural Repair ; : 15459683241257519, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38812378

RESUMO

BACKGROUND: Intensive task-oriented training has shown promise in enhancing distal motor function among patients with chronic stroke. A personalized electromyography (EMG)-driven soft robotic hand was developed to assist task-oriented object-manipulation training effectively. Objective. To compare the effectiveness of task-oriented training using the EMG-driven soft robotic hand. METHODS: A single-blinded, randomized controlled trial was conducted with 34 chronic stroke survivors. The subjects were randomly assigned to the Hand Task (HT) group (n = 17) or the control (CON) group (n = 17). The HT group received 45 minutes of task-oriented training by manipulating small objects with the robotic hand for 20 sessions, while the CON group received 45 minutes of hand-functional exercises without objects using the same robot. Fugl-Meyer assessment (FMA-UE), Action Research Arm Test (ARAT), Modified Ashworth Score (MAS), Box and Block test (BBT), Maximum Grip Strength, and active range of motion (AROM) of fingers were assessed at baseline, after intervention, and 3 months follow-up. The muscle co-contraction index (CI) was analyzed to evaluate the session-by-session variation of upper limb EMG patterns. RESULTS: The HT group showed more significant improvement in FMA-UE (wrist/hand, shoulder/elbow) compared to the CON group (P < .05). At 3-month follow-up, the HT group demonstrated significant improvements in FMA-UE, ARAT, BBT, MAS (finger), and AROMs (P < .05). The HT group exhibited a more significant decrease in muscle co-contractions compared to the CON group (P < .05). CONCLUSIONS: EMG-driven task-oriented training with the personalized soft robotic hand was a practical approach to improving motor function and muscle coordination. CLINICAL TRIAL REGISTRY NAME: Soft Robotic Hand System for Stroke Rehabilitation. CLINICAL TRIAL REGISTRATION-URL: https://clinicaltrials.gov/. UNIQUE IDENTIFIER: NCT03286309.

12.
Front Psychol ; 15: 1377430, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38659689

RESUMO

Introduction: Physical exercise is considered a useful non-pharmacological adjunctive treatment for promoting recovery from substance use disorders (SUD). However, adherence to physical exercise treatments is low, and little is known about what factors are associated with the initiation and maintenance of physical exercise behaviors. The aim of this study was to explore the psychosocial factors underlying these behaviors in individuals with SUD using an integrated theoretical model based on the health action process approach (HAPA) and the theory of planned behavior (TPB). Methods: A total of 1,197 individuals with SUDs (aged 37.20 ± 8.62 years) were recruited from 10 compulsory isolation drug rehabilitation centers in Zhejiang Province via convenience sampling according to a set of inclusion criteria. Self-reported data were collected to assess task self-efficacy (TSE), maintenance self-efficacy (MSE), recovery self-efficacy (RSE), outcome expectations (OE), action planning (AP), coping planning (CP), social support (SS), subjective norms (SN), attitude behavior (AB), behavioral intention (BI), perceived behavioral control (PBC), risk perception (RP), exercise stage, and exercise behavior in this integrated model. ANOVA and structural equation modeling (SEM) were used to evaluate this model. Results: One-way ANOVA revealed that the majority of the moderating variables were significantly different in the exercise phase. Further SEM showed that the model fit the data and revealed several important relationships. TSE, RP, SS, AB, and SN were indirectly associated with physical exercise behavior in individuals with SUD through the BI in the SUD initiation stage. In addition, PBC was directly related to physical exercise behavior in individuals with SUD. In the maintenance stage, MSE, AP, CP and exercise behavior were significantly related. Moreover, AP and CP were mediators of BI and MSE. Conclusion: This study is the first attempt to integrate patterns of physical exercise behavior in individuals with SUD. The HAPA-TPB integration model provides a useful framework for identifying determinants of physical exercise behavioral intentions and behaviors in individuals with SUD and for explaining and predicting the initiation and maintenance of physical exercise behaviors in these individuals. Moreover, the model provides scientific guidance for the enhancement of physical exercise adherence in individuals with SUD.

13.
World J Clin Cases ; 12(12): 2086-2091, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38680270

RESUMO

BACKGROUND: Venous variations are uncommon and usually hard to identify, and basilic vein variation is particularly rare. Basilic vein variation usually presents without any clinical symptoms and is often regarded as a benign alteration. This case was a patient with congenital basilic vein variation encountered during surgery for an infusion port. CASE SUMMARY: We documented and analyzed an uncommon anatomical variation in the basilic vein encountered during arm port insertion. This peculiarity has hitherto remained undescribed in the literature. We offer remedial strategies for addressing this anomaly in the future and precautionary measures to circumvent its occurrence. We conducted a comprehensive review of analogous cases in the literature, offering pertinent therapeutic recommendations and solutions, with the aim of enhancing the efficacy and safety of future arm port implantations. CONCLUSION: Venous variation is rare and requires detailed intraoperative and postoperative examination to ensure accuracy, so as not to affect subsequent treatment.

14.
Int Immunopharmacol ; 132: 111968, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38579565

RESUMO

BACKGROUND: Ulcerative colitis (UC) is an inflammatory disease whose pathogenesis and mechanisms have not been fully described. The m6A methylation modification is a general mRNA modification in mammalian cells and is closely associated with the onset and progression of inflammatory bowel disease (IBD). Palmatine (PAL) is a biologically active alkaloid with anti-inflammatory and protective effects in animal models of colitis. Accordingly, we examined the role of PAL on colitis by regulating N6-methyladenosine (m6A) methylation. METHODS: A rat experimental colitis model was established by 5 % dextran sulfate sodium (DSS) in drinking water for seven days, then PAL treatment was administered for seven days. The colonic tissue pathology was assessed using hematoxylin-eosin (HE) and disease activity index (DAI). In in vitro studies, a human, spontaneously immortalized non-cancerous colon mucosal epithelial cell line (NCM460) was exposed to 2 % DSS and treated with PAL and cell viability was assayed using Cell Counting Kit-8 (CCK-8). The levels of tumor necrosis factor α (TNF-α), interleukin (IL)-1ß, IL-6, and IL-8 were detected by enzyme-linked immunosorbent assay (ELISA) kits. The level of Zonula occludens-1 (ZO-1) was dectected by immunofluorescence. Transepithelial electrical resistance (TEER) of cells was also assessed. The methyltransferase-like 3 (METTL3), METTL14, AlkB homologate 5 (ALKBH5), and fat mass and obesity-associated protein (FTO) expression levels were assessed by western blotting. The localized expression of m6A was measured by immunofluorescence. RESULTS: PAL significantly prevented bodyweight loss and shortening of the colon in experimental colitis rats, as well as decreasing the DAI and histological damage scores. Furthermore, PAL inhibited the levels of inflammatory factors (TNF-α, IL-6, IL-8, and IL-1ß) in both DSS treated rats and NCM460 cells. In addition, PAL enhanced the expression level of ZO-1, and increased the transepithelial electrical resistance to repaire intestinal barrier dysfunction. Colitis occurred due to decreased m6A levels, and the increased FTO expression led to a colitis phenotype. PAL markedly enhanced the METTL3 and METTL14 expression levels while decreasing ALKBH5 and FTO expression levels. CONCLUSIONS: The findings demonstrated that PAL improved DSS-induced experimental colitis. This effect was associated with inhibiting FTO expression and regulating m6A methylation.


Assuntos
Adenosina/análogos & derivados , Dioxigenase FTO Dependente de alfa-Cetoglutarato , Alcaloides de Berberina , Citocinas , Sulfato de Dextrana , Modelos Animais de Doenças , Ratos Sprague-Dawley , Animais , Humanos , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Masculino , Alcaloides de Berberina/farmacologia , Alcaloides de Berberina/uso terapêutico , Citocinas/metabolismo , Ratos , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Colite Ulcerativa/metabolismo , Linhagem Celular , Colo/patologia , Colo/efeitos dos fármacos , Colo/metabolismo , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Mucosa Intestinal/metabolismo
15.
Inorg Chem ; 63(19): 8764-8774, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38686432

RESUMO

In-based halide perovskites have attracted a lot of attention because of their unique broadband emission properties. Herein, a series of In-based hybrid perovskites of (H2MP)2InCl7·H2O (1), (H2EP)2InCl7·H2O (2), (H2MP)2InBr7·H2O (3), and (H2EP)2InBr7·H2O (4) were synthesized under the control of halogen ions and organic cations. 1, 2, and 4 exhibit obvious photoluminescence properties with peaks at 392, 442, and 652 nm, respectively. The effects of the different components on the crystal structure and photoluminescence properties are discussed by calculating the structural distortion of the [InX6]3- octahedron. The photoluminescence properties of 1 and 4 were significantly improved after Sb3+ doping with PLQY values of 57.12 and 41.53%. Finally, a white LED was successfully fabricated with the two doped compounds coated onto the 365 nm blue LED chip.

16.
Heliyon ; 10(7): e28467, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38560270

RESUMO

Endocannabinoids (eCBs) exert considerable influence over energy metabolism, lipid metabolism, and glucose metabolism within the human body. Among the most biologically active cannabinoids identified thus far are 2-arachidonoylglycerol (2-AG), arachidonoyl ethanolamide (AEA), 1-stearoylglycerol (1-SRG), and stearoyl ethanolamide (SEA), which are derived from arachidonic acid (AA) and stearic acid (SA). However, despite the unique in bioactivities exhibited by eCBs, their determination in plasma has been hindered by the lack of sensitive analytical methods. The aim of this study was to develop and validate a highly sensitive and rapid method using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for accurate measurement of AEA, SEA, 2-AG, 1-SRG, AA, and SA levels in human plasma samples. Sample preparation involved a protein precipitation method and a methyl tert-butyl ether liquid-liquid extraction method. Chromatographic separation was accomplished by utilizing an ACQUITY UPLC BEH C8 column with a mobile phase of acetonitrile containing 0.1% formic acid and water containing 0.1% formic acid, flowing at a rate of 0.35 mL/min. AA-d8, 2-AG-d5, and AEA-d8 were selected as deuterated internal standards. The analytes were determined with MRM in both positive and negative ion mode. The lower limit of quantification ranged from 0.1 to 400 ng/mL, and the correlation coefficient (R2) was >0.99. Inter-day and intra-day precision exhibited values of 0.55-13.29% and 0.62%-13.90%, respectively. Recovery and matrix effect were within the range of 77.7%-109.7%, and 90.0%-113.5%, respectively. Stability tests confirmed the acceptability of all analytes. To demonstrate the effectiveness of the approach, it was implemented to assess and compare plasma samples from healthy volunteers (n = 49) and individuals with non-alcoholic fatty liver disease (NAFLD) (n = 62). The study revealed significant differences in AEA, SEA, AA, and SA levels between the two groups.

17.
J Control Release ; 369: 591-603, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38582336

RESUMO

Ischemia stroke is one of the leading causes of death and disability worldwide. Owing to the limited delivery efficiency to the brain caused by the blood-brain barrier (BBB) and off-target effects of systemic treatment, it is crucial to develop an in situ drug delivery system to improve the therapeutic effect in ischemic stroke. Briefly, we report a multifunctional in situ hydrogel delivery system for the co-delivery of reactive oxygen species (ROS)-responsive nanoparticles loaded with atorvastatin calcium (DSPE-se-se-PEG@AC NPs) and ß-nerve growth factor (NGF), which is expected to remodel pathological microenvironment for improving cerebral ischemia injury. The in vitro results exhibited the multifunctional hydrogel scavenged oxygen-glucose deprivation (OGD)-induced free radical, rescued the mitochondrial function, and maintained the survival and function of neurons, hence reducing neuronal apoptosis and neuroinflammation, consequently relieving ischemia injury in hippocampal neurons cell line (HT22). In the rat ischemia stroke model, the hydrogel significantly minified cerebral infarction by regulating inflammatory response, saving apoptotic neurons, and promoting angiogenesis and neurogenesis. Besides, the hydrogel distinctly improved the rats' neurological deficits after cerebral ischemia injury over the long-term observation. In conclusion, the in-situ hydrogel platform has demonstrated promising therapeutic effects in both in vitro and in vivo studies, indicating its potential as a new and effective therapy.


Assuntos
Atorvastatina , Isquemia Encefálica , Hidrogéis , Ratos Sprague-Dawley , Animais , Hidrogéis/administração & dosagem , Isquemia Encefálica/tratamento farmacológico , Masculino , Atorvastatina/administração & dosagem , Atorvastatina/uso terapêutico , Atorvastatina/farmacologia , Linhagem Celular , Espécies Reativas de Oxigênio/metabolismo , Nanopartículas/administração & dosagem , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/metabolismo , Fator de Crescimento Neural/administração & dosagem , Camundongos , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Ratos , Apoptose/efeitos dos fármacos , Polietilenoglicóis/química , Polietilenoglicóis/administração & dosagem , Sistemas de Liberação de Medicamentos , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/patologia
18.
Nat Commun ; 15(1): 3486, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664428

RESUMO

Van der Waals (vdW) assembly of low-dimensional materials has proven the capability of creating structures with on-demand properties. It is predicted that the vdW encapsulation can induce a local high-pressure of a few GPa, which will strongly modify the structure and property of trapped materials. Here, we report on the structural collapse of carbon nanotubes (CNTs) induced by the vdW encapsulation. By simply covering CNTs with a hexagonal boron nitride flake, most of the CNTs (≈77%) convert from a tubular structure to a collapsed flat structure. Regardless of their original diameters, all the collapsed CNTs exhibit a uniform height of ≈0.7 nm, which is roughly the thickness of bilayer graphene. Such structural collapse is further confirmed by Raman spectroscopy, which shows a prominent broadening and blue shift in the Raman G-peak. The vdW encapsulation-induced collapse of CNTs is fully captured by molecular dynamics simulations of the local vdW pressure. Further near-field optical characterization reveals a metal-semiconductor transition in accompany with the CNT structural collapse. Our study provides not only a convenient approach to generate local high-pressure for fundamental research, but also a collapsed-CNT semiconductor for nanoelectronic applications.

19.
Environ Health ; 23(1): 38, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38609943

RESUMO

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are known environmental contaminants with immunosuppressive properties. Their connection to rheumatoid arthritis (RA), a condition influenced by the immune system, is not well studied. This research explores the association between PFAS exposure and RA prevalence. METHODS: This research utilized data from the NHANES, encompassing a sample of 10,496 adults from the 2003-2018 cycles, focusing on serum levels of several PFAS. The presence of RA was determined based on self-reports. This study used multivariable logistic regression to assess the relationship between individual PFAS and RA risk, adjusting for covariates to calculate odds ratios (ORs). The combined effects of PFAS mixtures were evaluated using BKMR, WQS regression, and quantile g-computation. Additionally, sex-specific associations were explored through stratified analysis. RESULTS: Higher serum PFOA (OR = 0.88, 95% CI: 0.79, 0.98), PFHxS (OR = 0.91, 95% CI: 0.83, 1.00), PFNA (OR = 0.87, 95% CI: 0.77, 0.98), and PFDA (OR = 0.89, 95% CI: 0.81, 0.99) concentration was related to lower odds of RA. Sex-specific analysis in single chemical models indicated the significant inverse associations were only evident in females. BKMR did not show an obvious pattern of RA estimates across PFAS mixture. The outcomes of sex-stratified quantile g-computation demonstrated that an increase in PFAS mixture was associated with a decreased odds of RA in females (OR: 0.76, 95% CI: 0.62, 0.92). We identified a significant interaction term of the WQS*sex in the 100 repeated hold out WQS analysis. Notably, a higher concentration of the PFAS mixture was significantly associated with reduced odds of RA in females (mean OR = 0.93, 95% CI: 0.88, 0.98). CONCLUSIONS: This study indicates potential sex-specific associations of exposure to various individual PFAS and their mixtures with RA. Notably, the observed inverse relationships were statistically significant in females but not in males. These findings contribute to the growing body of evidence indicating that PFAS may have immunosuppressive effects.


Assuntos
Artrite Reumatoide , Fluorocarbonos , Adulto , Feminino , Masculino , Humanos , Inquéritos Nutricionais , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/epidemiologia , Razão de Chances , Autorrelato
20.
Nature ; 628(8009): 758-764, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38538800

RESUMO

Van der Waals encapsulation of two-dimensional materials in hexagonal boron nitride (hBN) stacks is a promising way to create ultrahigh-performance electronic devices1-4. However, contemporary approaches for achieving van der Waals encapsulation, which involve artificial layer stacking using mechanical transfer techniques, are difficult to control, prone to contamination and unscalable. Here we report the transfer-free direct growth of high-quality graphene nanoribbons (GNRs) in hBN stacks. The as-grown embedded GNRs exhibit highly desirable features being ultralong (up to 0.25 mm), ultranarrow (<5 nm) and homochiral with zigzag edges. Our atomistic simulations show that the mechanism underlying the embedded growth involves ultralow GNR friction when sliding between AA'-stacked hBN layers. Using the grown structures, we demonstrate the transfer-free fabrication of embedded GNR field-effect devices that exhibit excellent performance at room temperature with mobilities of up to 4,600 cm2 V-1 s-1 and on-off ratios of up to 106. This paves the way for the bottom-up fabrication of high-performance electronic devices based on embedded layered materials.

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