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1.
Nanomicro Lett ; 16(1): 268, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39136800

RESUMO

The eye, a complex organ isolated from the systemic circulation, presents significant drug delivery challenges owing to its protective mechanisms, such as the blood-retinal barrier and corneal impermeability. Conventional drug administration methods often fail to sustain therapeutic levels and may compromise patient safety and compliance. Polysaccharide-based microneedles (PSMNs) have emerged as a transformative solution for ophthalmic drug delivery. However, a comprehensive review of PSMNs in ophthalmology has not been published to date. In this review, we critically examine the synergy between polysaccharide chemistry and microneedle technology for enhancing ocular drug delivery. We provide a thorough analysis of PSMNs, summarizing the design principles, fabrication processes, and challenges addressed during fabrication, including improving patient comfort and compliance. We also describe recent advances and the performance of various PSMNs in both research and clinical scenarios. Finally, we review the current regulatory frameworks and market barriers that are relevant to the clinical and commercial advancement of PSMNs and provide a final perspective on this research area.

2.
Proc Natl Acad Sci U S A ; 121(34): e2407285121, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39133859

RESUMO

Discovering and engineering herbicide-resistant genes is a crucial challenge in crop breeding. This study focuses on the 4-hydroxyphenylpyruvate dioxygenase Inhibitor Sensitive 1-Like (HSL) protein, prevalent in higher plants and exhibiting weak catalytic activity against many ß-triketone herbicides (ß-THs). The crystal structures of maize HSL1A complexed with ß-THs were elucidated, identifying four essential herbicide-binding residues and explaining the weak activity of HSL1A against the herbicides. Utilizing an artificial evolution approach, we developed a series of rice HSL1 mutants targeting the four residues. Then, these mutants were systematically evaluated, identifying the M10 variant as the most effective in modifying ß-THs. The initial active conformation of substrate binding in HSL1 was also revealed from these mutants. Furthermore, overexpression of M10 in rice significantly enhanced resistance to ß-THs, resulting in a notable 32-fold increase in resistance to methyl-benquitrione. In conclusion, the artificially evolved M10 gene shows great potential for the development of herbicide-resistant crops.


Assuntos
Resistência a Herbicidas , Herbicidas , Oryza , Proteínas de Plantas , Oryza/genética , Oryza/metabolismo , Resistência a Herbicidas/genética , Herbicidas/farmacologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Melhoramento Vegetal/métodos , Plantas Geneticamente Modificadas/genética , Mutação
3.
Int J Ophthalmol ; 17(8): 1431-1436, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39156785

RESUMO

AIM: To describe the surgical procedure of fusiform penetrating keratoplasty (FPK) using multiple trephines of different sizes for treating patients with severe infectious keratitis. METHODS: Fourteen eyes underwent FPK, and 15 eyes received conventional penetrating keratoplasty (PK) were included in the study. The best-corrected visual acuity (BCVA), refractive outcomes, endothelial cell density, and postoperative complications were recorded. RESULTS: The FPK group was followed for an average of 15.3±2.1mo, whereas the PK group was followed for 16.1±1.9mo. The corneal ulcers were elliptical-shaped in all 14 eyes in the FPK group. The mean BCVA (logMAR, 0.26±0.13) showed no statistically significant differences from that in the PK group (logMAR, 0.21±0.12, P>0.05) at 1y after surgery. But the mean curvature, mean astigmatism, and mean spherical equivalent in the FPK group were lower than those in the PK group (P<0.05). Peripheral anterior synechia was observed in one patient in the FPK group, whereas 6 patients in the PK group. Suture loosening and neovascularization were observed in 4 and 5 eyes in the PK group, respectively. No graft immune rejection or elevation of intraocular pressure was observed in the two groups. CONCLUSION: For patients with elliptical-shaped corneas or corneal ulcers, FPK can avoid disrupting of corneal limbus, reduce the risk of postoperative complications, and can result in satisfactory visual quality.

4.
Environ Sci Technol ; 58(31): 13636-13647, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-38961559

RESUMO

Emerging data suggest a close correlation between ambient fine particle (AFP) exposure and eye disorders and pinpoint potential threats of AFPs to eye health in humans. However, the possible passage (including direct intrusion) and the interactions of AFPs with the eye microenvironment in addition to morphological and physiological injuries remain elusive. To this end, the likely transport of AFPs into the eyes via blood-ocular barrier (BOB) in humans and animals was investigated herein. Exogenous particles were recognized inside human eyes with detailed structural and chemical fingerprints. Importantly, comparable AFPs were found in sera with constant structural and chemical fingerprints, hinting at the translocation pathway from blood circulation into the eye. Furthermore, we found that the particle concentrations in human eyes from patients with diabetic retinopathy were much higher than those from patients with no fundus pathological changes (i.e., myopia), indicating that the damaged BOB increased the possibility of particle entrance. Our diseased animal model further corroborated these findings. Collectively, our results offer a new piece of evidence on the intrusion of exogenous particles into human eyes and provide an explanation for AFP-induced eye disorders, with substantially increased risk in susceptible individuals with BOB injuries.


Assuntos
Material Particulado , Humanos , Animais , Olho/patologia , Masculino
5.
Opt Lett ; 49(14): 4006-4009, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39008763

RESUMO

We achieved an ultrahigh Q surface lattice resonance (SLR) using a conventional U-shaped split ring resonator (U-SRR) array. Numerical results confirmed by semi-analytical analysis show that with the transmission resonance amplitude up to 0.8, the Q-factor of the SLR can still surpass 104. The physical mechanisms of the ultrahigh Q-factor were also investigated. Besides the radiation suppression provided by conventional SLR, the unique geometry of the U-SRR can further offer dual radiation suppression mechanisms: reduction of the dipole moment and excitation of the in-plane quadrupole. We expect that the proposed ultrahigh Q SLR platform will be explored for more flexible and advanced nanoscale devices.

6.
Insects ; 15(7)2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-39057196

RESUMO

This study addresses the challenges in plant pest and disease prediction within the context of smart agriculture, highlighting the need for efficient data processing techniques. In response to the limitations of existing models, which are characterized by slow training speeds and a low prediction accuracy, we introduce an innovative prediction method that integrates gene expression programming (GEP) with support vector machines (SVM). Our approach, the gene expression programming-support vector machine (GEP-SVM) model, begins with encoding and fitness function determination, progressing through cycles of selection, crossover, mutation, and the application of a convergence criterion. This method uniquely employs individual gene values as parameters for SVM, optimizing them through a grid search technique to refine genetic parameters. We tested this model using historical data on wheat blossom midges in Shaanxi Province, spanning from 1933 to 2010, and compared its performance against traditional methods, such as GEP, SVM, naive Bayes, K-nearest neighbor, and BP neural networks. Our findings reveal that the GEP-SVM model achieves a leading back-generation accuracy rate of 90.83%, demonstrating superior generalization and fitting capabilities. These results not only enhance the computational efficiency of pest and disease prediction in agriculture but also provide a scientific foundation for future predictive endeavors, contributing significantly to the optimization of agricultural production strategies.

7.
Toxics ; 12(7)2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39058167

RESUMO

In this study, we investigated whether rutaecarpine could aggravate acetaminophen-induced acute liver damage in vivo and in vitro. CCK-8 and apoptosis assays were performed to verify the cytotoxicity of acetaminophen to L02 cells with or without rutaecarpine. The expression levels of the target proteins and genes were determined using Western blotting and qRT-PCR. The liver pathological changes were evaluated with hematoxylin and eosin staining, while the aspartate aminotransferase (AST) and alanine aminotransferase (AST) levels in plasma were measured to assess the liver damage. Our results revealed that pretreatment of the cell and mice with rutaecarpine significantly aggravated the acetaminophen-induced liver damage. Mechanistically, rutaecarpine induces the CYP1A2 protein, which accelerates the metabolism of acetaminophen to produce a toxic intermediate, N-acetyl-p-benzoquinone imine (NAPQI), leading to severe liver inflammation. Rutaecarpine exacerbated the liver damage by upregulating CYP1A2 and proinflammatory factors. These findings highlight the importance of carefully considering the dosage of rutaecarpine when combined with acetaminophen in drug design and preclinical trials.

8.
J Am Chem Soc ; 146(31): 21903-21912, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39046794

RESUMO

In photoelectrochemical (PEC) cells, selective oxidation of organic substrates coupled with hydrogen evolution represents a promising approach for value-added chemical production and solar energy conversion. In this study, we report on PEC epoxidation of alkenes at a ruthenium dye-sensitized photoanode in a CH3CN/H2O mixed solvent with LiBr as a mediator and water as the oxygen source. The dye-sensitized photoanode was found to exhibit significant advantages in the simultaneous improvement of charge separation and suppression of charge recombination. First, LiBr as a redox mediator plays a critical role in charge separation, leading to an excellent excited electron injection efficiency of 95% and a high dye regeneration efficiency of 87%. Second, the predominant charge recombination pathway on the dye-sensitized photoanode is efficiently blocked by the reaction between alkene and the in situ generated bromine oxidant. As a result, the current system achieved a remarkable photocurrent density of over 4 mA cm-2 with a record-high incident photo-to-current efficiency (IPCE) of 51% and extraordinary selectivity of up to 99% for the epoxidation of a wide range of alkenes. Meanwhile, nearly 100% Faradaic efficiency for hydrogen evolution was obtained. The performance shown here exceeds that obtained by metal oxide-based semiconductor photoanodes under comparable conditions, demonstrating the great potential of dye-sensitized photoelectrodes for organic synthesis owing to their diversity and tunability.

9.
Sci Rep ; 14(1): 17553, 2024 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-39080459

RESUMO

Osteoarthritis (OA) is a chronic disease due to the deterioration of cartilage structure and function, involving the progressive degradation of the cartilage extracellular matrix. Cathepsins, lysosomal cysteine proteases, play pivotal roles in various biological and pathological processes, particularly in protein degradation. Excess cathepsins levels are reported to contribute to the development of OA. However, the causal relationship between the cathepsin family and knee and hip OA remains uncertain. Therefore, this study utilized bidirectional Mendelian Randomization (MR) analyses to explore this causal association. Our results indicated that elevated serum levels of cathepsin O increase the overall risk of knee OA, while increased serum levels of cathepsin H enhance the risk of hip OA. Conversely, the reverse MR analyses did not reveal a reverse causal relationship between them. In summary, OA in different anatomical locations may genetically result from pathological elevations in different serum cathepsin isoforms, which could be utilized as diagnostic and therapeutic targets in clinical practice.


Assuntos
Catepsinas , Análise da Randomização Mendeliana , Osteoartrite do Quadril , Osteoartrite do Joelho , Humanos , Osteoartrite do Quadril/genética , Osteoartrite do Quadril/sangue , Osteoartrite do Quadril/diagnóstico , Catepsinas/sangue , Catepsinas/genética , Osteoartrite do Joelho/genética , Osteoartrite do Joelho/sangue , Osteoartrite do Joelho/diagnóstico , Predisposição Genética para Doença , Feminino , Masculino , Polimorfismo de Nucleotídeo Único , Biomarcadores/sangue
10.
J Pediatr Endocrinol Metab ; 37(8): 734-740, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39026465

RESUMO

OBJECTIVES: Pseudohypoparathyroidism (PHP) comprises a cluster of heterogeneous diseases characterized by hypocalcemia and hyperphosphatemia due to parathyroid hormone (PTH) resistance. PHP type 1B (PHP1B) is caused by heterozygous maternal deletions within GNAS or STX16. STX16 exon 2-6 deletion is commonly observed in autosomal dominant (AD)-PHP1B, while sporadic PHP1B commonly results from methylation abnormalities of maternal differentially methylated regions and remains unclear at the molecular level. CASE PRESENTATION: A 39-year-old male patient with PHP1B, who had his first seizure at 15 years of age, presented to our hospital. The methylation-specific multiplex ligation-dependent probe amplification results showed a half-reduced copy number of STX16 exon 5-7 and loss of methylation at GNAS exon A/B. His mother also had a half-reduced copy number of STX16 exon 5-7 but with normal methylation of GNAS. His father has a normal copy number of STX16 and normal methylation of GNAS. CONCLUSIONS: For the recognition and early diagnosis of this kind of disease, here we report the clinical symptoms, auxiliary examinations, genetic testing characteristics, and treatment of the patient.


Assuntos
Éxons , Pseudo-Hipoparatireoidismo , Sintaxina 16 , Humanos , Masculino , Pseudo-Hipoparatireoidismo/genética , Pseudo-Hipoparatireoidismo/complicações , Adulto , Sintaxina 16/genética , Éxons/genética , Deleção de Sequência , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Prognóstico , Cromograninas/genética
11.
Molecules ; 29(11)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38893484

RESUMO

To better assess the practical value and avoid potential risks of the traditionally medicinal and edible basidiomycete Schizophyllum commune, which may arise from undescribed metabolites, a combination of elicitors was introduced for the first time to discover products from cryptic and low-expressed gene clusters under laboratory cultivation. Treating S. commune NJFU21 with the combination of five elicitors led to the upregulated production of a class of unusual linear diterpene-derived variants, including eleven new ones (1-11), along with three known ones (12-14). The structures and stereochemistry were determined by 1D and 2D NMR, HRESIMS, ECD, OR and VCD calculations. Notably, the elongation terminus of all the diterpenes was decorated by an unusual butenedioic acid moiety. Compound 1 was a rare monocyclic diterpene, while 2-6 possessed a tetrahydrofuran moiety. The truncated metabolites 4, 5 and 13 belong to the trinorditerpenes. All the diterpenes displayed approximately 70% scavenging of hydroxyl radicals at 50 µM and null cytotoxic activity at 10 µM. In addition, compound 1 exhibited potent antifungal activity against the plant pathogenic fungi Colletotrichum camelliae, with MIC values of 8 µg/mL. Our findings indicated that this class of diterpenes could provide valuable protectants for cosmetic ingredients and the lead compounds for agricultural fungicide development.


Assuntos
Diterpenos , Schizophyllum , Diterpenos/farmacologia , Diterpenos/química , Diterpenos/metabolismo , Schizophyllum/metabolismo , Schizophyllum/genética , Estrutura Molecular , Regulação para Cima/efeitos dos fármacos , Humanos
12.
Front Public Health ; 12: 1352176, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38846603

RESUMO

Objective: To analyze the epidemiological characteristics and wound healing conditions of common unintentional skin lacerations in children. Methods: A retrospective analysis was conducted on data from 1,107 children, aged 0-12 years, with skin lacerations who received emergency treatment at Qilu Hospital of Shandong University from January 1, 2019, to December 30, 2022. Data on age, injury site, time from injury to suturing, and wound healing conditions were statistically analyzed. Results: Among the 1,107 cases, 714 (64.5%) were male and 393 (35.5%) were female, with a male-to-female ratio of 1.8:1; median age was 5 years (IQR, 3-7). Infants and toddlers (0-3 years old) constituted the highest proportion, accounting for 36.3% (402 cases). The number of children aged over 3 years gradually decreased with increasing age. In younger children, the most common injuries were to the forehead, scalp, and lower jaw; in school-aged children, the proportion of limb and trunk injuries significantly increased. Age (OR, 1.34; 95% CI, 1.23-1.46), outdoor injuries (OR, 2.21; 95% CI, 1.18-4.16), lower limb injuries (OR, 5.35; 95% CI, 2.86-10.00), and wound length greater than 3 cm (OR, 10.65; 95% CI, 5.02-22.60) were significant risk factors for poor wound healing. The risk of poor wound healing increased by 34% for each additional year of age. Conclusion: In children, the common sites of unintentional skin lacerations show distinct age and gender distribution characteristics. Older age, outdoor injuries, longer wound lengths, and lower limb injuries are independent risk factors for poor wound healing.


Assuntos
Lacerações , Cicatrização , Humanos , Masculino , Feminino , Pré-Escolar , Lactente , Estudos Retrospectivos , Criança , China/epidemiologia , Lacerações/epidemiologia , Recém-Nascido , Fatores de Risco , Lesões Acidentais/epidemiologia , Ferimentos e Lesões/epidemiologia
13.
Huan Jing Ke Xue ; 45(6): 3186-3195, 2024 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-38897742

RESUMO

This study primarily focused on the regional disparities in both water quality criteria and ecological risks attributed to cadmium presence within the surface waters of the Yangtze River Basin. In the initial phase, the long-term water quality criteria for cadmium were recalibrated in accordance with the guidelines outlined in China's "Water Quality Criteria for Freshwater Aquatic Organisms-Cadmium," accounting for the prevalent hardness distribution within the Yangtze River Basin's surface water. Subsequently, a more refined revision was undertaken considering the specific characteristics of the species residing within the Yangtze River Basin. This undertaking led to a comprehensive interpretation of the regional variations in both the distribution of long-term water quality criteria values and the risk quotient distribution of cadmium throughout the Yangtze River Basin. The incorporation of hardness and species-specific attributes resulted in a revised range of long-term water quality criteria for cadmium across different urban locales within the Yangtze River Basin. Notably, the recalibrated values ranged from 0.08 µg·L-1 as the lowest threshold to 0.75 µg·L-1 as the upper limit, signifying a tenfold differentiation. Correspondingly, the urban average annual risk quotient associated with cadmium exposure demonstrated a variation from 0.035 to 1.12, marking a significant 32-fold discrepancy between the lowest and highest values. It is essential to highlight that regions of paramount importance, such as the confluence area connecting the upper and middle stretches of the Yangtze River Basin and the intricate Dongting Lake system, exhibited noteworthy ecological risks attributed to cadmium presence. Consequently, further in-depth investigations into these critical regions are imperative for a comprehensive understanding of the associated risks.

14.
Sci Rep ; 14(1): 14650, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918414

RESUMO

An air spring (AS) for ships must have the structural strength of its bellows enhanced considerably to ensure its reliability under high internal pressure and strong impact. In this case, the stiffness of the bellows gradually dominates the overall stiffness of the AS. Nevertheless, the parameterization calculation of stiffness for an AS mainly focuses on its pneumatic stiffness. The bellows stiffness is normally analyzed by virtue of equivalent simplification or numeric simulation. There is not an effective parameterization calculation model for the stiffness of the bellows, making it difficult to achieve the structural optimization design of the bellows. In this paper, the shell theory was borrowed to build a mechanical model for the bellows. Subsequently, the state vector of the bellows was solved by precision integration and boundary condition. Iteration was conducted to identify the complex coupling relationship between the vector of the bellows and other parameters. On this basis, the parameterization calculation method was introduced for the stiffness of the bellows to obtain the vertical and horizontal stiffness of the AS. After that, a dual-membrane low-stiffness structure was designed to analyze the dominating factors affecting the strength and stiffness of the AS, which highlighted the way to the low-stiffness optimization design of high-strength ASs. In the end, three prototypes and one optimized prototype were tested to verify the correctness of the parameterization design model for stiffness as well as the effectiveness of the structural optimization design.

15.
Zhongguo Gu Shang ; 37(6): 5765-82, 2024 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-38910380

RESUMO

OBJECTIVE: To explore clinical effect of single small incision with honeycomb titanium plate in treating acute acromioclavicular dislocation. METHODS: The clinical data of 40 patients with acute acromioclavicular dislocation admitted from December 2019 to December 2021 were retrospectively analyzed and divided into two groups according to different surgical methods. Among them, 20 patients were fixed with single small incision with honeycomb titanium plate (titanium plate group), including 11 males and 9 females, aged from 23 to 65 years old with an average of (47.40±12.58) years old;12 patients on the left side, 8 patients on the right side;11 patients with type Ⅲ, 3 patients with type Ⅳ, and 6 patients with type Ⅴ according to Rockwood classification. Twenty patients were fixed with clavicular hook plate (clavicular hook group), including 8 males and 12 females, aged from 24 to 65 years old with an average of (48.40±12.08) years old;12 patients on the left side, 8 patients on the right side;10 patients with type Ⅲ, 2 patients with type Ⅳ, and 8 patients with type Ⅴ according to Rockwood classification. Operative time, incision length, intraoperative blood loss, hospital stay, visual analogue scale (VAS) and Constant-Murley score of shoulder joint function were compared between two groups. Anteroposterior radiographs of the affected shoulder joint were recorded before, immediately and 6 months after surgery, and the coracoclavicular distance was measured and compared. RESULTS: Both groups of patients were successfully completed operation without serious complications. All patients were followed up for 6 to 15 months with an average of (11.9±4.8) months. There were no incisional infection, internal plant fracture or failure, bone tunnel fracture and other complications occurred. The incision length of titanium plate group (35.90±3.14) mm was significantly shorter than that of clavicular hook group (49.30±3.79) mm (P<0.05). There were no significant difference in operative time, intraoperative blood loss and hospital stay between two groups (P>0.05). At 1 and 3 months after operation, VAS of titanium plate group was lower than that of clavicular hook group (P<0.05). Connstant-Murley scores in titanium plate group at 1, 3 and 6 months after operation were (86.80±1.36), (91.60±2.32) and (94.90±2.22), respectively;and in clavicular hook group were (78.45±5.47), (85.55±2.01) and (90.25±1.92), which were higher than that of clavicular hook group (P<0.05). There was no significant difference in coracoclavicular distance between two groups immediately and 6 months after operation(P>0.05). CONCLUSION: For the treatment of acute acromioclavicular joint dislocation, single small incision combined with honeycomb titanium plate have advantages of shorter incision, fast recovery of shoulder joint function without the second operation, and has good satisfaction of patient.


Assuntos
Articulação Acromioclavicular , Placas Ósseas , Titânio , Humanos , Masculino , Articulação Acromioclavicular/cirurgia , Articulação Acromioclavicular/lesões , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Estudos Retrospectivos , Luxações Articulares/cirurgia , Adulto Jovem , Fixação Interna de Fraturas/métodos
17.
Entropy (Basel) ; 26(5)2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38785654

RESUMO

We proposed and verified a scheme of chaos synchronization for integrated five-section semiconductor lasers with matching parameters. The simulation results demonstrated that the integrated five-section semiconductor laser could generate a chaotic signal within a large parameter range of the driving currents of five sections. Subsequently, chaos synchronization between two integrated five-section semiconductor lasers with matched parameters was realized by using a common noise signal as a driver. Moreover, it was found that the synchronization was sensitive to the current mismatch in all five sections, indicating that the driving currents of the five sections could be used as keys of chaotic optical communication. Therefore, this synchronization scheme provides a candidate to increase the dimension of key space and enhances the security of the system.

18.
Front Public Health ; 12: 1398340, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38799676

RESUMO

Active mobility, such as cycling and walking, is assuming a growing significance in the daily lives of urban residents in China due to its positive impact on health and the environment. The impact of the COVID-19 epidemic has elicited significant changes in behaviors, perceptions, and intellectual viewpoints in this domain, potentially altering residents' physical activities in the long-term. This scoping review seeks to delve into the multi-dimensional influence of the epidemic on active mobility in urban China. A thorough investigation of English and Chinese studies up to January 2024 was conducted, drawing from articles in Web of Science and the Chinese National Knowledge Infrastructure. Only empirical studies providing knowledge into this subject were selected in the review, which comprised 20 studies in total. This review indicates that the influence of COVID-19 on active urban mobility in China has exhibited contradictory outcomes in terms of behavior. Besides, the experiences during the epidemic have significantly shaped citizens' attitudes and understanding of active mobility. The repercussions of the epidemic and the ensuing restrictions exacerbate the existing challenges faced by women, particularly those who are married, the older adult, and individuals with low incomes. The results exhibit both resemblances and idiosyncrasies when juxtaposed with prior research conducted in different nations. This analysis also offers valuable insights for improving active mobility across individual, organizational, and socio-political realms. The current state of empirical understanding in this field underscores the need for further research endeavors employing diverse methodological approaches and increased emphasis on the transformations anticipated in the post-epidemic era.


Assuntos
COVID-19 , População Urbana , Humanos , COVID-19/epidemiologia , China/epidemiologia , População Urbana/estatística & dados numéricos , Exercício Físico , Caminhada/estatística & dados numéricos , SARS-CoV-2 , Feminino , Masculino
19.
Artigo em Inglês | MEDLINE | ID: mdl-38670447

RESUMO

As a major mental health disorder, symptoms of schizophrenia (SCZ) include delusions, reduced motivation, hallucinations, reduced motivation and a variety of cognitive disabilities. Many of these symptoms are now known to be associated with abnormal regulation of the immune system. Low blood levels of cytokines and chemokines have been suggested to be one of the underlying causes of SCZ. However, their biological roles at different stages of SCZ remain unclear. Our objective was to investigate expression patterns of cytokines and chemokines at different stages of onset and relapse in SCZ patients and to conduct an analysis of their relationship to disease progression. We also aimed to identify immune features associated with different disease trajectories in patients with SCZ. Gene set enrichment analysis (GSEA) was used to interrogate the GSE27383 dataset and identify key genes associated with inflammation. These results led us to recruit 36 healthy controls, 40 patients with first-episode psychosis (FEP), and 39 patients with SCZ relapse. Meso Scale Discovery technology was used to independently validate serum levels of 35 cytokines and chemokines. This was followed by a meta-analysis to gain a more comprehensive understanding of the role of interleukin-8 (IL-8/CXCL8) in SCZ. Analysis of the GSE27383 database revealed 3596 genes with distinct expression patterns. A significant portion of these genes were identified as inflammation-related and showed remarkable enrichment in three key pathways: IL-17, cytokine-cytokine receptor, and AGE-RAGE signaling in diabetic complications. We observed co-expression of CXCL8 and IL-16 within these three pathways. In a subsequent analysis of independently validated samples, a notable discrepancy was detected in the inflammatory status between individuals experiencing FEP and those in relapse. In particular, expression of CXCL8 demonstrated superior predictive capability in FEP and relapsed patients. Notably, results of the meta-analysis confirmed that Chinese and European populations were consistent with the overall results (Z = 4.60, P < 0.001; Z = 3.70, P < 0.001). However, in the American subgroup, there was no significant difference in CXCL8 levels between patients with SCZ compared to healthy controls (Z = 1.09, P = 0.277). Our findings suggest that the inflammatory response in patients with SCZ differs across the different stages, with CXCL8 emerging as a potential predictive factor. Collectively, our data suggest that CXCL8 has the potential to serve as a significant immunological signature of SCZ subtypes. Trial registration: The clinical registration number for this trial is ChiCTR2100045240 (Registration Date: 2021/04/09).


Assuntos
Interleucina-8 , Recidiva , Esquizofrenia , Humanos , Esquizofrenia/sangue , Esquizofrenia/genética , Interleucina-8/sangue , Adulto , Feminino , Masculino , Adulto Jovem , Citocinas/sangue , Citocinas/genética
20.
Am J Transplant ; 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38648890

RESUMO

The activation of innate immunity following transplantation has been identified as a crucial factor in allograft inflammation and rejection. However, the role of cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)/stimulator of interferon genes (STING) signaling-mediated innate immunity in the pathogenesis of allograft rejection remains unclear. Utilizing a well-established murine model of corneal transplantation, we demonstrated increased expression of cGAS and STING in rejected-corneal allografts compared with syngeneic (Syn) and normal (Nor) corneas, along with significant activation of the cGAS/STING pathway, as evidenced by the enhanced phosphorylation of TANK-binding kinase 1and interferon regulatory factor 3. Pharmacological and genetic inhibition of cGAS/STING signaling markedly delayed corneal transplantation rejection, resulting in prolonged survival time and reduced inflammatory infiltration. Furthermore, we observed an increase in the formation of neutrophil extracellular traps (NETs) in rejected allografts, and the inhibition of NET formation through targeting peptidylarginine deiminase 4 and DNase I treatment significantly alleviated immune rejection and reduced cGAS/STING signaling activity. Conversely, subconjunctival injection of NETs accelerated corneal transplantation rejection and enhanced the activation of the cGAS/STING pathway. Collectively, these findings demonstrate that NETs contribute to the exacerbation of allograft rejection via cGAS/STING signaling, highlighting the targeting of the NETs/cGAS/STING signaling pathway as a potential strategy for prolonging allograft survival.

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