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1.
Rev Sci Instrum ; 95(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38597747

RESUMO

Substation electrical equipment generates a massive number of infrared images during operation. However, the overall quality of the infrared images is low and it lacks image detail information. When using traditional target detection algorithms for detection, feature extraction poses great difficulties. Therefore, to address this problem, this paper proposes a target detection algorithm based on the improved faster region-based convolutional neural network (Faster R-CNN). It achieves the correct identification of different types of electrical equipment in infrared images. First, the algorithm improves the backbone network of Faster R-CNN for feature extraction. An InResNet structure is proposed to replace the residual block structure of the original ResNet-34 network, which enhances the richness of feature extraction. Second, the rectified linear unit activation function in the original feature extraction network is replaced by the exponential linear unit activation function, and group normalization is used instead of batch normalization as the network normalization method. Then, the dense connection structure is introduced into the ResNet-34 network, and the whole network is called residual dense connection network. Finally, the improved Faster R-CNN is compared to the original Faster R-CNN, a single-shot multibox detector, and you only look once v3 plus spatial pyramid pooling. The experimental results show that the improved algorithm has the highest mean average precision and average recall for most of the substation electrical equipment in infrared images. Moreover, from the confidence level of the detected electrical equipment and the accuracy of the prediction box, the improved Faster R-CNN has the best performance.

2.
Nat Prod Res ; : 1-7, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38629157

RESUMO

Icariin is the most bioactive ingredient of Epimedium L. and a quality marker of Herba Epimedii. Conventional methods for production of Icariin are known to be inefficient, resulting in low yields and significant environmental pollution. This study aimed to develop a sustainable and effective biphasic enzymatic hydrolysis system for the efficient conversion of epimedin C to icariin. The biphasic system was created using butyl acetate and phosphate buffer (pH 4.5) at a ratio of 3:1 (V/V) along with α-L-rhamnosidase/epimedin C (2 U/1 mg) at 50 °C for 12 h. Consequently, 98.21% of epimedin C was hydrolysed to icariin, with 95.62% of the product being transferred to the organic phase. Even after four cycles of use, the conversion ratio remained high at 75.28%. Furthermore, this novel strategy was also used for the conversion of Epimedium brevicornu Maxim. extracts. The biphasic system represents a sustainable and effective method for icariin production, offering potential benefits for industrial applications.

3.
Adv Healthc Mater ; : e2400747, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38652737

RESUMO

The efficient delivery of therapeutic proteins to tumor sites is a promising cancer treatment modality. Hydrogen-bonded organic frameworks (HOFs) have been successfully used for the protective encapsulation of proteins; however, easy precipitation and lack of controlled release of existing HOFs limit their further application for protein delivery in vivo. In this study, a hypoxia-responsive HOF, self-assembled from azobenzenedicarboxylate/polyethylene glycol-conjugated azobenzenedicarboxylate and tetrakis(4-amidiniumphenyl)methane through charge-assisted hydrogen-bonding, is developed for systemic protein delivery to tumor cells. The newly generated HOF platform efficiently encapsulates representative cytochrome C, demonstrating good dispersibility under physiological conditions. Moreover, it can respond to overexpressed reductases in the cytoplasm under hypoxic conditions, inducing fast intracellular protein release to exert therapeutic effects. The strategy presented herein can be applied to other therapeutic proteins and can be expanded to encompass more intrinsic tumor microenvironment stimuli. This offers a novel avenue for utilizing HOFs in protein-based cancer therapy. This article is protected by copyright. All rights reserved.

4.
J Hazard Mater ; 470: 134182, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38583202

RESUMO

Establishing an economic and sustained Fenton oxidation system to enhance sludge dewaterability and carbamazepine (CBZ) removal rate is a crucial path to simultaneously achieve sludge reduction and harmless. Leveraging the principles akin to "tea making", we harnessed tea waste to continually release tea polyphenols (TP), thus effectively maintaining high level of oxidation efficiency through the sustained Fenton reaction. The results illustrated that the incorporation of tea waste yielded more favorable outcomes in terms of water content reduction and CBZ removal compared to direct TP addition within the Fe(III)/hydrogen peroxide (H2O2) system. Concomitantly, this process mainly generated hydroxyl radical (•OH) via three oxidation pathways, effectively altering the properties of extracellular polymeric substances (EPS) and promoting the degradation of CBZ from the sludge mixture. The interval addition of Fe(III) and H2O2 heightened extracellular oxidation efficacy, promoting the desorption and removal of CBZ. The degradation of EPS prompted the transformation of bound water to free water, while the formation of larger channels drove the discharge of water. This work achieved the concept of treating waste with waste through using tea waste to treat sludge, meanwhile, can provide ideas for subsequent sludge harmless disposal.


Assuntos
Carbamazepina , Peróxido de Hidrogênio , Ferro , Oxirredução , Esgotos , Chá , Poluentes Químicos da Água , Carbamazepina/química , Peróxido de Hidrogênio/química , Chá/química , Esgotos/química , Ferro/química , Poluentes Químicos da Água/química , Matriz Extracelular de Substâncias Poliméricas/química , Matriz Extracelular de Substâncias Poliméricas/metabolismo , Eliminação de Resíduos Líquidos/métodos , Compostos Férricos/química , Polifenóis/química
7.
Br J Haematol ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632670

RESUMO

Splenectomy is an effective treatment for immune thrombocytopenia (ITP). The effect of COVID-19 vaccination on splenectomized patients with ITP during the COVID-19 pandemic has not been reported. Therefore, this study aimed to investigate the effect of COVID-19 vaccination on clinical outcomes in these patients. This was a longitudinal study of splenectomized patients with ITP. A total of 191 splenectomized patients were included in this study. After a median follow-up of 114 months, 146 (76.4%) patients had a sustained response to splenectomy. During COVID-19 infection, vaccinated patients showed a lower risk of severe infections (odds ratio [OR], 0.13; 95% confidence interval [CI]: 0.05-0.36; p < 0.001), hospitalization (OR, 0.13; 95% CI, 0.04-0.48; p = 0.002), and ITP exacerbation (OR, 0.16; 95% CI, 0.04-0.67; p = 0.012). These findings indicate that COVID-19 vaccination plays a protective role in splenectomized patients with ITP.

8.
World J Gastrointest Oncol ; 16(4): 1268-1280, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38660670

RESUMO

BACKGROUND: Immunotherapy for advanced gastric cancer has attracted widespread attention in recent years. However, the adverse reactions of immunotherapy and its relationship with patient prognosis still need further study. In order to determine the association between adverse reaction factors and prognosis, the aim of this study was to conduct a systematic prognostic analysis. By comprehensively evaluating the clinical data of patients with advanced gastric cancer treated by immunotherapy, a nomogram model will be established to predict the survival status of patients more accurately. AIM: To explore the characteristics and predictors of immune-related adverse reactions (irAEs) in advanced gastric cancer patients receiving immunotherapy with programmed death protein-1 (PD-1) inhibitors and to analyze the correlation between irAEs and patient prognosis. METHODS: A total of 140 patients with advanced gastric cancer who were treated with PD-1 inhibitors in our hospital from June 2021 to October 2023 were selected. Patients were divided into the irAEs group and the non-irAEs group according to whether or not irAEs occurred. Clinical features, manifestations, and prognosis of irAEs in the two groups were collected and analyzed. A multivariate logistic regression model was used to analyze the related factors affecting the occurrence of irAEs, and the prediction model of irAEs was established. The receiver operating characteristic (ROC) curve was used to evaluate the ability of different indicators to predict irAEs. A Kaplan-Meier survival curve was used to analyze the correlation between irAEs and prognosis. The Cox proportional risk model was used to analyze the related factors affecting the prognosis of patients. RESULTS: A total of 132 patients were followed up, of whom 63 (47.7%) developed irAEs. We looked at the two groups' clinical features and found that the two groups were statistically different in age ≥ 65 years, Ki-67 index, white blood cell count, neutrophil count, and regulatory T cell (Treg) count (all P < 0.05). Multivariate logistic regression analysis showed that Treg count was a protective factor affecting irAEs occurrence (P = 0.030). The ROC curve indicated that Treg + Ki-67 + age (≥ 65 years) combined could predict irAEs well (area under the curve = 0.753, 95% confidence interval: 0.623-0.848, P = 0.001). Results of the Kaplan-Meier survival curve showed that progression-free survival (PFS) was longer in the irAEs group than in the non-irAEs group (P = 0.001). Cox proportional hazard regression analysis suggested that the occurrence of irAEs was an independent factor for PFS (P = 0.006). CONCLUSION: The number of Treg cells is a separate factor that affects irAEs in advanced gastric cancer patients receiving PD-1 inhibitor immunotherapy. irAEs can affect the patients' PFS and result in longer PFS. Treg + Ki-67 + age (≥ 65 years old) combined can better predict the occurrence of adverse reactions.

9.
J Adv Res ; 2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38626873

RESUMO

INTRODUCTION: Obesity-induced bone loss affects the life quality of patients all over the world. Irisin, one of the myokines, plays an essential role in bone and fat metabolism. OBJECTIVE: Investigate the effects of irisin on bone metabolism via adipocytes in the bone marrow microenvironment. METHODS: In this study, we fed fibronectin type III domain-containing protein 5 (FNDC5, the precursor protein of irisin) knockout mice (FNDC5-/-) with a high-fat diet (HFD) for 10 weeks. The quality of bone mass was assessed by micro-CT analysis, histological staining, and dynamic bone formation. In vitro, the lipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was assayed by Oil Red O staining, and the osteogenic differentiation was assayed by alkaline phosphatase staining. Meanwhile, the gene expression in the BMSC-differentiated adipocytes by RNA sequence and the involved pathway of irisin were determined by western blot and qRT-PCR were performed. RESULTS: The FNDC5-/- mice fed with a HFD showed an increased body weight, fat content of the bone marrow and bone, and a decreased bone formation compared with those with a standard diet (SD). In vitro, irisin inhibited the differentiation of BMSCs into adipocytes and alleviated the inhibition of osteogenesis derived from BMSCs by the adipocyte supernatant. RNA sequence and blocking experiment showed that irisin reduced the production of interleukin 6 (IL-6) in adipocytes through downregulating the TLR4/MyD88/NF-κB pathway. Immunofluorescence staining of bone marrow further confirmed an increased IL-6 expression in the FNDC5-/- mice fed with HFD compared with those fed with SD, which suffered serious bone loss. CONCLUSION: Irisin downregulates activation of the TLR4/MyD88/NF-κB pathway, thereby reducing IL-6 production in adipocytes to enhance the osteogenesis of BMSCs. Thus, the rescue of osteogenesis of BMSCs, initially inhibited by IL-6, is a potential therapeutic target to mitigate obesity-induced osteoporosis.

10.
Sex Med ; 12(1): qfae008, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38487305

RESUMO

Background: Aildenafil citrate is a potent and selective inhibitor of cyclic guanosine monophosphate-specific phosphodiesterase type 5, developed for the treatment of erectile dysfunction (ED). Aim: This study aimed to assess the pharmacokinetics, safety, and tolerability of aildenafil citrate tablets after multiple doses in healthy Chinese males. Methods: Twenty participants were divided into 2 groups, 10 participants each. Participants were administered multiple doses of aildenafil citrate tablets at 30 and 60 mg. Outcomes: The safety evaluation was based on clinical symptoms and adverse events. Concentrations of aildenafil and its key metabolites (M1, M5, and M12) in human serum were measured by liquid chromatography-tandem mass spectrometry. Results: Pharmacokinetic analysis showed rapid absorption and elimination of aildenafil, with a median time to maximum serum concentration of 1 hour and mean terminal half-lives of 2.75 and 3.26 hours in the respective dose groups. The mean maximum concentration was proportional to the aildenafil dose in the range of 30 to 60 mg, although the area under the curve was not proportional for serum concentration vs time 0 to the last measurable time point (24 hours). Multiple doses of aildenafil were well tolerated, with 60.0% of men experiencing treatment-emergent adverse events, notably myalgia and fatigue, particularly in the 60-mg group. Clinical Implications: Aildenafil citrate tablets demonstrated favorable tolerability with once-daily administration over the clinical dose range. The occurrence of myalgia and fatigue was more prevalent in the 60-mg group. From a pharmacokinetic perspective, optimal administration of aildenafil citrate tablets appears to be 1 hour before sexual intercourse in men with ED. Strengths and Limitations: This study presents robust safety and pharmacokinetic data at expected therapeutic doses, unaffected by clinical factors. The efficacy of aildenafil citrate tablets warrants further validation in individuals with ED. Conclusion: Aildenafil citrate tablets exhibited good tolerability in healthy Chinese males following multiple doses at 30 and 60 mg. The 60-mg group showed an increased incidence of myalgia and fatigue, suggesting the need for heightened clinical vigilance. The mean maximum concentration, but not the area under the curve, displayed dose proportionality within the 30- to 60-mg dose range, and no significant drug accumulation was observed with repeated daily administration. Clinical Trial Registration: CTR20192473 (http://www.chinadrugtrials.org.cn).

11.
J Vasc Surg Venous Lymphat Disord ; : 101862, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38428502

RESUMO

OBJECTIVE: This study aimed to characterize radiographic characteristics on computed tomography venography and risk factors of inferior vena cava thrombosis (IVCT) in situ after retrievable vena cava filter (VCF) placement. METHODS: Between September 2018 and June 2023, a single-center retrospective cohort study was conducted in patients with or without IVCT in situ following VCF placement. Patient baseline demographics, presentation of lower extremity deep vein thrombosis (LEDVT), thrombus characteristics, concurrent pulmonary embolism, comorbidities and risk factors for LEDVT, and IVC and VCF-related information were collected and analysed. Univariable analysis followed by multivariable analysis was performed to evaluate the odds ratio (OR) with a 95% confidence interval (CI). RESULTS: One hundred and seventeen eligible patients were included, regionally isolated filling-defect surrounding the support pillars of VCF and contacting IVC wall on computed tomography venography images were identified, clots were more frequently found on the minor axis or anterior wall of IVC. Univariable analyses suggested that the incidence of IVCT in situ (31.6%, 37/117) was closely associated with age (P = .001), thrombus limb (left (P = .001) and bilateral side (P = .001)), hypertension (P = .008), filter shapes (P < .001), short IVC diameter (P = .009) or magnification percentage (P = .004), and long IVC diameter (P = .006). Multivariable analyses suggested that bilateral side LEDVT (OR, 4.92; 95% CI, 1.56-15.51; P = .007) and increased short IVC magnification percentage (OR, 1.01; 95% CI, 1.00-1.03; P = .013) statistically significant increase the IVCT in situ risk, whereas increased age (OR, 0.96; 95% CI, 0.94-0.99; P = .013) and short IVC diameter (OR, 0.87; 95% CI, 0.77-0.98; P = .026) were associated with decreased odds against IVCT in situ. CONCLUSIONS: IVCT in situ represents regionally isolated filling-defect at points of filter contact with IVC wall. Bilateral side LEDVT and increased short IVC magnification percentage may be potential risk factors impacting the occurrence of IVCT in situ, while increased age and short IVC diameter may decrease the incidence of IVCT in situ and seem to be protective factor against IVCT in situ emergence.

12.
Acad Radiol ; 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38480075

RESUMO

RATIONALE AND OBJECTIVES: This study aimed to investigate the relationship between minimum inferior vena cava (IVC) diameter magnification percentage and in-situ IVC thrombosis (iIVCT) after inferior vena cava filter (IVCF) placement in lower extremity deep vein thrombosis (LEDVT). METHODS: This was a single center retrospective study. Study sample consisted of patients with LEDVT who received computed tomography venography of IVC both before and after IVCF placement between January 2019 and October 2023. A propensity score matching (PSM) was also used in covariates including age, hypertension, and thrombus limbs. Multivariate Cox regression analyses were performed to mitigate the impact of selection bias and control for potential confounding variables. The incremental changes associated with minimum IVC diameter magnification percentage and iIVCT were evaluated with restricted cubic spines (RCS). RESULTS: 113 LEDVT patients (age 58.8 ± 17.8 years, 57.5% male) were included. Multivariate Cox regression analyses revealed a significant positive association between the minimum IVC diameter magnification percentage and the incidence of iIVCT after adjusting for the age, hypertension, and thrombus limbs (adjusted hazard risk [HR] = 1.02, 95% CI, 1.01 to 1.02, p < .001), suggesting minimum IVC diameter magnification percentage was an independent risk factor for iIVCT. Moreover, after using PSM, the association remained significant (HR=1.01, 95% CI, 1.01 to 1.02, p < .001). RCS analysis showed a non-linear dose-response association (s-shaped fitting curve) between minimum IVC diameter magnification percentage and iIVCT risk (nonlinear p = .041). The fitting curve indicated a threshold effect (overall p = .005), with a smaller magnification percentage being negatively associated with the incidence of iIVCT, presenting continuously decreasing HR at levels of magnification percentage < 37.3%. CONCLUSION: A decreasing minimum IVC diameter magnification percentage is consistently associated with a decreasing risk of iIVCT following IVCF placement when the percentage is < 37.3%, indicating that it is a protective factor against iIVCT incidence. WHAT THIS PAPER ADDS?: This single-center retrospective study, which designed to investigate the relationship between minimum inferior vena cava diameter magnification percentage and in-situ inferior vena cava thrombosis (iIVCT) following inferior vena cava filter (IVCF) placement in lower extremity deep vein thrombosis in 113 patients, demonstrated that decreasing minimum IVC diameter magnification percentage is consistently associated with a decreasing risk of iIVCT following IVCF placement when the percentage is < 37.3%, indicating that it is a protective factor against iIVCT incidence.

13.
Biomaterials ; 306: 122475, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38306733

RESUMO

Although tumor-infiltrating T lymphocytes (TIL-Ts) play a crucial role in solid tumor immunotherapy, their clinical application has been limited because of the immunosuppressive microenvironment. Herein, we developed an injectable hydrogel microsphere-integrated training court (MS-ITC) to inspire the function of TIL-Ts and amplify TIL-Ts, through grafting with anti-CD3 and anti-CD28 antibodies and bovine serum albumin nanoparticles encapsulated with IL-7 and IL-15. MS-ITC provided the T-cell receptor and co-stimulatory signals required for TIL-Ts activation and IL-7/IL-15 signals for TIL-Ts expansion. Afterward, the MS-ITC was injected locally into the osteosarcoma tumor tissue in mice. MS-ITC suppressed the growth of primary osteosarcoma by more than 95 %, accompanied with primed and expanded TIL-Ts in the tumor tissues, compromising significantly increased CD8+ T and memory T cells, thereby enhancing the anti-tumor effect. Together, this work provides an injectable hydrogel microsphere-integrated training platform capable of inspiring TIL-Ts potential for a range of solid tumor immunotherapy.


Assuntos
Interleucina-15 , Neoplasias , Animais , Camundongos , Hidrogéis , Interleucina-7 , Microesferas , Citotoxicidade Imunológica , Linfócitos do Interstício Tumoral , Linfócitos T , Interleucina-2/farmacologia , Ativação Linfocitária , Microambiente Tumoral
14.
Bioorg Med Chem Lett ; 102: 129675, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38417632

RESUMO

NLRP3 is an intracellular sensor protein that detects a broad range of danger signals and environmental insults. Its activation results in a protective pro-inflammatory response designed to impair pathogens and repair tissue damage via the formation of the NLRP3 inflammasome. Assembly of the NLRP3 inflammasome leads to caspase 1-dependent secretory release of the pro-inflammatory cytokines IL-1ß and IL-18 as well as to gasdermin d-mediated pyroptotic cell death. Herein, we describe the discovery of a novel indazole series of high affinity, reversible inhibitors of NLRP3 activation through screening of DNA-encoded libraries and the potent lead compound 3 (BAL-0028, IC50 = 25 nM) that was identified directly from the screen. SPR studies showed that compound 3 binds tightly (KD range 104-123 nM) to the NACHT domain of NLRP3. A CADD analysis of the interaction of compound 3 with the NLRP3 NACHT domain proposes a binding site that is distinct from those of ADP and MCC950 and includes specific site interactions. We anticipate that compound 3 (BAL-0028) and other members of this novel indazole class of neutral inhibitors will demonstrate significantly different physical, biochemical, and biological properties compared to NLRP3 inhibitors previously identified.


Assuntos
Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Sulfonamidas , Citocinas/metabolismo , Interleucina-1beta/metabolismo , Caspase 1 , DNA
15.
Psychiatry Res ; 334: 115816, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38412712

RESUMO

Non-suicidal self-injury (NSSI) is a significant public health problem, but there is no consistent evidence of its risk factors. One possibility is that there are subtypes NSSI that have different risk factors and clinical symptoms. In this review we evaluated the evidence of subtypes to determine if there were consistent subtypes of NSSI that emerged across studies. Four databases (Medline; Embase; PsycINFO; Web of Science) were searched to identify studies that used data-driven approaches and were published before November 9, 2022. There were 21 studies with 23 unique samples for review. Most of the included studies used NSSI symptoms or personal characteristics as the subtyping indicators, revealing 2-5 subtypes of NSSI. Variations in subtyping indicators, sample characteristics, and statistical methods may have contributed to the inconsistent number and characteristics of subtypes across studies. A new conceptual framework is proposed to integrate these diverse findings, highlighting the important roles of NSSI function and psychological pain in differentiating NSSI subtypes. This framework sheds light on the differences among self-injurers and offers insights for future endeavors to address the complexities of NSSI.


Assuntos
Comportamento Autodestrutivo , Humanos , Comportamento Autodestrutivo/psicologia , Fatores de Risco , Gerenciamento de Dados , Bases de Dados Factuais
16.
J Agric Food Chem ; 72(6): 2935-2942, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38317284

RESUMO

Sclerotinia stem rot (SSR) caused by the phytopathogenic fungus Sclerotinia sclerotiorum has led to serious losses in the yields of oilseed rape and other crops every year. Here, we designed and synthesized a series of carboxamide derivatives containing a diphenyl ether skeleton by adopting the scaffold splicing strategy. From the results of the mycelium growth inhibition experiment, inhibition rates of compounds 4j and 4i showed more than 80% to control S. sclerotiorum at a dose of 50 µg/mL, which is close to that of the positive control (flubeneteram, 95%). Then, the results of a structure-activity relationship study showed that the benzyl scaffold was very important for antifungal activity and that introducing a halogen atom on the benzyl ring would improve antifungal activity. Furthermore, the results of an in vitro activity test suggested that these novel compounds can inhibit the activity of succinate dehydrogenase (SDH), and the binding mode of 4j with SDH was basically similar to that of the flutolanil derivative. Morphological observation of mycelium revealed that compound 4j could cause a damage on the mycelial morphology and cell structure of S. sclerotiorum, resulting in inhibition of the growth of mycelia. Furthermore, in vivo antifungal activity assessment of 4j displayed a good control of S. sclerotiorum (>97%) with a result similar to that of the positive control at a concentration of 200 mg/L. Thus, the diphenyl ether carboxamide skeleton is a new starting point for the discovery of new SDH inhibitors and is worthy of further development.


Assuntos
Ascomicetos , Brassica napus , Fungicidas Industriais , Antifúngicos/farmacologia , Ascomicetos/metabolismo , Relação Estrutura-Atividade , Brassica napus/metabolismo , Succinato Desidrogenase/metabolismo , Fungicidas Industriais/farmacologia , Fungicidas Industriais/química
17.
Int J Biol Macromol ; 261(Pt 2): 129862, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38309409

RESUMO

Osteoarthritis is a long-term degenerative condition of the joints that is characterized by the breakdown of cartilage and inflammation of the synovial membrane. The presence of an inflammatory microenvironment and the degradation of the extracellular matrix produced by chondrocytes leads to the aggravation of cartilage injury, hindering the treatment of osteoarthritis. A promising approach to address this issue is to apply a combined strategy that is sensitive to the specific conditions in osteoarthritic joints and possesses properties that can reduce inflammation and promote cartilage healing. Here, inspired by the structure of chocolate-covered peanuts, we developed an injectable, environment-responsive bilayer hydrogel microsphere using microfluidics technology. The microsphere applied chondroitin sulfate methacryloyl (ChsMA) as its core and was coated with a methacryloyl gelatin (GelMA) shell that was loaded with celecoxib (CLX) liposomes (ChsMA+CLX@Lipo@GelMA). CLX was released from the liposomes when the GelMA shell rapidly degraded in response to the osteoarthritic microenvironment and suppressed the generation of inflammatory agents, demonstrating a beneficial impact of the outer shell in reducing inflammation. While the inner methacryloyl microsphere core degraded, chondroitin sulfate was released to promote chondrocyte anabolism and facilitate cartilage repair. Thus, the synthesized bilayer hydrogel microspheres hold great potential for treating osteoarthritis.


Assuntos
Hidrogéis , Osteoartrite , Humanos , Hidrogéis/química , Gelatina/química , Sulfatos de Condroitina , Microesferas , Lipossomos , Osteoartrite/tratamento farmacológico , Inflamação
18.
Chin Med ; 19(1): 21, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38310315

RESUMO

Traditional Chinese medicine (TCM) has been widely used for several centuries for metabolic diseases, including non-alcoholic fatty liver disease (NAFLD). At present, NAFLD has become the most prevalent form of chronic liver disease worldwide and can progress to non-alcoholic steatohepatitis (NASH), cirrhosis, and even hepatocellular carcinoma. However, there is still a lack of effective treatment strategies in Western medicine. The development of NAFLD is driven by multiple mechanisms, including genetic factors, insulin resistance, lipotoxicity, mitochondrial dysfunction, endoplasmic reticulum stress, inflammation, gut microbiota dysbiosis, and adipose tissue dysfunction. Currently, certain drugs, including insulin sensitizers, statins, vitamin E, ursodeoxycholic acid and betaine, are proven to be beneficial for the clinical treatment of NAFLD. Due to its complex pathogenesis, personalized medicine that integrates various mechanisms may provide better benefits to patients with NAFLD. The holistic view and syndrome differentiation of TCM have advantages in treating NAFLD, which are similar to the principles of personalized medicine. In TCM, NAFLD is primarily classified into five types based on clinical experience. It is located in the liver and is closely related to spleen and kidney functions. However, due to the multi-component characteristics of traditional Chinese medicine, its application in the treatment of NAFLD has been considerably limited. In this review, we summarize the advances in the pathogenesis and treatment of NAFLD, drawn from both the Western medicine and TCM perspectives. We highlight that Chinese and Western medicine have complementary advantages and should receive increased attention in the prevention and treatment of NAFLD.

19.
Int Ophthalmol ; 44(1): 20, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38324035

RESUMO

PURPOSE: Death-to-preservation time (DTP) is a commonly reported, but infrequently studied, measure of efficiency for the corneal tissue procurement process and is a key screening component for corneal tissue suitability for transplantation. It is unknown whether demographic factors such as race, age, or gender may affect DTP. METHODS: This retrospective cross-sectional study included all deceased-donor eye tissue collected by CorneaGen Eye Banks between June 1, 2012 and June 30, 2016. Exposure variables of race, age, and gender were independently analyzed with the outcome variable, DTP, using three simple linear regression analyzes. Associations were then confirmed by a multiple linear regression analysis within a single model. RESULTS: A total of 24,138 unique donors were identified from 48,207 donor eyes. Simple linear regression analysis showed that relative to White donors, Black and Hispanic donors were associated with a 2.40 h (95% CI 2.07-2.74 h, p < 0.001) and 2.48 h (95% CI 2.15-2.80 h, p < 0.001) longer mean DTP, respectively. DTP decreased with increasing age, at a rate of 30 min per every 10 years (95% CI 27-33 min, p < 0.001). Male donors were associated with a 35 min (95% CI 26-44 min, p < 0.001) longer DTP relative to female donors. A multiple linear regression confirmed the results of the three simple linear regressions. CONCLUSIONS: In a large cohort of corneal donors, non-White race, younger age, and male gender were associated with longer DTP.


Assuntos
Córnea , Doadores de Tecidos , Humanos , Feminino , Masculino , Criança , Estudos Transversais , Estudos Retrospectivos , Demografia
20.
Environ Sci Atmos ; 4(2): 265-274, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38371605

RESUMO

Aerosols formed and grown by gas-to-particle processes are a major contributor to smog and haze in megacities, despite the competition between growth and loss rates. Rapid growth rates from ammonium nitrate formation have the potential to sustain particle number in typical urban polluted conditions. This process requires supersaturation of gas-phase ammonia and nitric acid with respect to ammonium nitrate saturation ratios. Urban environments are inhomogeneous. In the troposphere, vertical mixing is fast, and aerosols may experience rapidly changing temperatures. In areas close to sources of pollution, gas-phase concentrations can also be highly variable. In this work we present results from nucleation experiments at -10 °C and 5 °C in the CLOUD chamber at CERN. We verify, using a kinetic model, how long supersaturation is likely to be sustained under urban conditions with temperature and concentration inhomogeneities, and the impact it may have on the particle size distribution. We show that rapid and strong temperature changes of 1 °C min-1 are needed to cause rapid growth of nanoparticles through ammonium nitrate formation. Furthermore, inhomogeneous emissions of ammonia in cities may also cause rapid growth of particles.

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