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1.
Sci China Life Sci ; 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38561483

RESUMO

A common approach in therapeutic protein development involves employing synthetic ligands with multivalency, enabling sophisticated control of signal transduction. Leveraging the emerging concept of liquid-liquid phase separation (LLPS) and its ability to organize cell surface receptors into functional compartments, we herein have designed modular ligands with phase-separation modalities to engineer programmable interreceptor communications and precise control of signal pathways, thus inducing the rapid, potent, and specific apoptosis of tumor cells. Despite their simplicity, these "triggers", named phase-separated Tumor Killers (hereafter referred to as psTK), are sufficient to yield interreceptor clustering of death receptors (represented by DR5) and tumor-associated receptors, with notable features: LLPS-mediated robust high-order organization, well-choreographed conditional activation, and broad-spectrum capacity to potently induce apoptosis in tumor cells. The development of novel therapeutic proteins with phase-separation modalities showcases the power of spatially reorganizing signal transduction. This approach facilitates the diversification of cell fate and holds promising potential for targeted therapies against challenging tumors.

2.
Medicine (Baltimore) ; 103(14): e37633, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38579084

RESUMO

BACKGROUND: The quality control circle (QCC) model has achieved good results in clinical applications in many hospitals in China and has gained popularity. This study aims to explore the application of QCC activities on early ambulation after cesarean section. METHODS: A QCC management group was established following standardized methods and techniques. The theme of the group was identified as "to enhance the implementation rate of the patient early ambulation after the cesarean section" through a matrix graph. The early ambulation rates after surgery of patients who received cesarean section were compared before and after QCC managements. RESULTS: Our data suggested that the early ambulation rates after cesarean section increased from 37.5% to 81.25% after applying QCC management. The biggest factor influencing the ambulation activities 24 ±â€…4 hours after the surgery was patients and family members do not cooperate. In addition, outstanding improvements in terms of nurses' sense of responsibility and self-confidence, communication and teamwork capacity in the problem-solving process were observed after the establishment of QCC. CONCLUSION: The application of QCC management had not only increase the early ambulation rates after cesarean section but also improved the quality of nursery care in general.


Assuntos
Cesárea , Deambulação Precoce , Humanos , Gravidez , Feminino , Hospitais , Controle de Qualidade , China
3.
Math Biosci Eng ; 21(3): 3944-3966, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38549314

RESUMO

We proposed a novel decision-making method, the large-scale group consensus multi-attribute decision-making method based on probabilistic dual hesitant fuzzy sets, to address the challenge of large-scale group multi-attribute decision-making in fuzzy environments. This method concurrently accounted for the membership and non-membership degrees of decision-making experts in fuzzy environments and the corresponding probabilistic value to quantify expert decision information. Furthermore, it applied to complex scenarios involving groups of 20 or more decision-making experts. We delineated five major steps of the method, elaborating on the specific models and algorithms used in each phase. We began by constructing a probabilistic dual hesitant fuzzy information evaluation matrix and determining attribute weights. The following steps involved classifying large-scale decision-making expert groups and selecting the optimal classification scheme based on effectiveness assessment criteria. A global consensus degree threshold was established, followed by implementing a consensus-reaching model to synchronize opinions within the same class of expert groups. Decision information was integrated within and between classes using an information integration model, leading to a comprehensive decision matrix. Decision outcomes for the objects were then determined through a ranking method. The method's effectiveness and superiority were validated through a case study on urban emergency capability assessment, and its advantages were further emphasized in comparative analyses with other methods.

4.
Sci Total Environ ; 926: 171942, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38527553

RESUMO

Wastewater reclaim in industrial parks can effectively reduce the dependence on external water resources, few literatures evaluated the reclaim system from perspectives of economy, technology, and environmental impact. It is very popular across China that a constructed wetland is linked with a wastewater plant and then discharged the tailwater into surface waters, based on current situation, pilot experiment, and other available techniques, six scenarios for wastewater reclaim system were designed for Shanghai Chemical Industrial Park. Using life cycle assessment, it was found that in scenario of pilot experiment, most environmental impact was derived from wastewater plant and ultra filtration - reverse osmosis, in which ultra filtration - reverse osmosis accounted >20 % for POCP, AP, and EP, Wastewater plant accounted >86 % for ADP, ODP. It was showed that electricity and sludge were most important parameters affecting LCA, when electricity consumption was reduced by 20 %, total standardized environmental impact would be changed in the range of 1.40 %-1.65 %, the most significant change was HTP (6.12 %-6.32 %) when 20 % up and downward change in sludge amount, followed by MAETP (5.27 %-5.36 %). A multi-criteria decision-making analysis was conducted on all the scenarios based on environmental impact, life cycle cost, technical efficiency, it was showed that the scenario designed for pilot experiment was the best available technique, which was consisted of wastewater plant, hybrid constructed wetland, ultra-filtration and reverse osmosis, and reused as desalted water. A wastewater reclaim plant is suggested from the result of this paper. It was believed that this study could provide references for construction of wastewater reclaim system in industrial parks of the world.

5.
J Nanobiotechnology ; 22(1): 103, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38468261

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) is a prevalent inflammatory autoimmune disease characterised by persistent inflammation and joint damage with elevated levels of reactive oxygen species (ROS). Current treatment modalities for RA have significant limitations, including poor bioavailability, severe side effects, and inadequate targeting of inflamed joints. Herein, we synthesised cerium/manganese oxide nanoparticles (NPs) as efficient drug carriers with antioxidant and catalytic-like functions that can eliminate ROS to facilitate the polarization of macrophages phenotype from M1 to M2 and alleviate inflammation. Methotrexate (MTX), a first-line RA medication, was loaded into the NPs, which were further modified with bovine serum albumin (BSA) and integrated into dissolving hyaluronic acid-based microneedles (MNs) for transdermal delivery. RESULT: This innovative approach significantly enhanced drug delivery efficiency, reduced RA inflammation, and successfully modulated macrophage polarization toward an anti-inflammatory phenotype. CONCLUSION: This research not only presents a promising drug delivery strategy for RA but also contributes broadly to the field of immune disease treatment by offering an advanced approach for macrophage phenotypic reprogramming.


Assuntos
Artrite Reumatoide , Cério , Compostos de Manganês , Nanopartículas , Óxidos , Humanos , Manganês/farmacologia , Espécies Reativas de Oxigênio/farmacologia , Artrite Reumatoide/tratamento farmacológico , Macrófagos , Inflamação , Cério/farmacologia
6.
J Pept Sci ; : e3572, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38396336

RESUMO

Hairy tofu is a famous Chinese snack that is made from soybeans and rich in various nutrients. In order to further explore the antioxidant peptides of hairy tofu hydrolysates, seven proteases were used to hydrolyze hairy tofu. The results of in vitro radical scavenging activity showed that hairy tofu hydrolysates obtained by pancreatin exhibited the highest antioxidant activity. After Sephadex G-25 gel filtration and reversed-phase high-performance liquid chromatography (RP-HPLC), 97 peptides were identified in the most antioxidant fraction using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Among them, nine peptides were synthesized and their antioxidant activities were assessed using a H2 O2 -induced oxidative 293T cell model. Finally, four peptides (QCESHK, LAWNEGR, NLQGENEWDQK, and FTEMWR) at concentrations of < 50 µg/ml significantly decreased the malondialdehyde content compared with the model group, displaying in vivo antioxidant activity and low cytotoxicity. Overall, this research provided the choice of using hairy tofu peptides as antioxidant products in the pharmaceutical and food industries.

7.
Sci Total Environ ; 916: 170196, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38246376

RESUMO

In this study, hydrochar (HCR) was used to alleviate high ammonia inhibition to the anaerobic digestion (AD) of waste activated sludge (WAS) and to elucidate the inner microorganism mechanism. After HCR addition, the cumulative methane yield increased by 73.6 % and 35.6 % under ammonia inhibition levels of 3000 and 6000 mg/L, respectively. Metagenomic analysis showed that HCR enriched the diversity of hydrogenotrophic methanotrophs, and the relative abundances of functional microorganisms with electron transfer capabilities (Geobacteraceae bacterium etc.) were 1.5-7.8 times higher than those without HCR addition. Metabolomics analysis implied that metabolites related to fatty acid degradation, such as glutaric acid and hexadecanal, were downregulated (2.9-15.7 %) under ammonia inhibition conditions and that HCR regulates metabolites in the methane metabolic pathway. Moreover, HCR changed the methanogenic pathway from hydrogenotrophic methanogenesis to multiple pathways under ammonia inhibition conditions, especially methanolic and methylotrophic methanogenesis, which facilitated the methane yield. This study provides valuable information for understanding the inner microbial mechanism of HCR addition on alleviating high ammonia inhibition to AD of WAS, and gives basic knowledge for the application of AD of WAS under ammonia inhibition conditions.


Assuntos
Amônia , Esgotos , Esgotos/microbiologia , Anaerobiose , Reatores Biológicos/microbiologia , Metano , Nitrogênio
8.
J Adv Res ; 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38065407

RESUMO

INTRODUCTION: The proportion of animal based foods in daily diet of consumers is constantly increasing, with chicken being highly favored due to its high protein and low fat characteristics. The consumption of chicken around the world is steadily increasing. Intramuscular fat (IMF) is a key indicator affecting meat quality. OBJECT: High IMF content can contribute to improve the quality of chicken meat. The regulatory mechanism of IMF deposition in chicken is poorly understood, so its complete elucidation is essential to improve chicken meat quality. METHOD: Here, we performed whole genome resequencing on 516 yellow feather chickens and single-cell RNA sequencing on 3 63-day-old female JXY chickens. In addition, transcriptome sequencing techniques were also performed on breast muscle tissue of JXY chickens at different developmental stages. And 13C isotope tracing technique was applied. RESULTS: In this study, a large-scale genetic analysis of an IMF-selected population and a control population identified fatty acid synthase (FASN) as a key gene for improving IMF content. Also, contrary to conventional view, de novo lipogenesis (DNL) was deemed to be an important contributor to IMF deposition. As expected, further analyses by isotope tracing and other techniques, confirmed that DNL mainly occurs in myocytes, contributing about 40% of the total fatty acids through the regulation of FASN, using the available FAs as substrates. Additionally, we also identified a relevant causal mutation in the FASN gene with effects on FA composition. CONCLUSION: These findings contribute to the understanding of fat metabolism in muscle tissue of poultry, and provide the feasible strategy for the production of high-quality chicken meat.

9.
J Thorac Dis ; 15(10): 5494-5506, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37969306

RESUMO

Background: Tuberculosis (TB) remains a significant global health emergency caused by Mycobacterium tuberculosis (Mtb). The epidemiology, transmission, genotypes, mutational patterns, and clinical consequences of TB have been extensively studied worldwide, however, there is a lack of information regarding the epidemiology and mutational patterns of Mtb in Pakistan, specifically concerning the prevalence of multi-drug resistant TB (MDR-TB). Methods: This study aimed to investigate the incidence of Mtb and associated mutational patterns using the line probe assay (LPA). Previous studies have reported a high frequency of mutations in the rpoB, inhA, and katG genes, which are associated with resistance to rifampicin (RIF) and isoniazid (INH). Therefore, the current study utilized LPA to detect mutations in the rpoB, katG, and inhA genes to identify multi-drug resistant Mtb. Results: LPA analysis of a large pool of Mtb isolates, including samples from 241 sputum-positive patients, revealed that 34.85% of isolates were identified as MDR-TB, consistent with reports from various regions worldwide. The most prevalent mutations observed were rpoB S531L and inhA promoter C15T, which were associated with resistance to RIF and INH, respectively. Conclusions: This study highlights the effectiveness of GenoType MTBDRplus and MTBDRsl assays as valuable tools for TB management. These assays enable rapid detection of resistance to RIF, INH, and fluoroquinolones (FQs) in Mtb clinical isolates, surpassing the limitations of solid and liquid media-based methods. The findings contribute to our understanding of MDR-TB epidemiology and provide insights into the genetic profiles of Mtb in Pakistan, which are essential for effective TB control strategies.

10.
Food Res Int ; 174(Pt 1): 113637, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37986482

RESUMO

Foods differing in fat content can be distinguished through olfaction alone. The mechanisms underlying the ability of humans to discriminate between foods differing in fat content through olfaction are underexplored. In this study, beef and pork samples were prepared (raw and roasted) with low (muscle tissue; raw: 2-5%; roasted: 5%), medium (muscle tissue with lard; raw: 25-30%; roasted: 36-44%), and high (lard; raw: 40-42%; roasted: 69-70%) fat content. Olfactory triangle discrimination tests and ranking tests were performed to explore whether humans can discriminate and rank fat content of the samples through orthonasal olfaction. Headspace-Solid Phase Micro Extraction-Gas Chromatography-Mass Spectrometry (SPME-GC-MS) was used to characterize the volatile compound composition of the headspace of samples differing in fat content. Partial least-squares regression and partial least squares-discriminant analysis were performed to determine the volatile compounds that were responsible for olfactory fat content discrimination. We found that fat content in both raw and roasted samples can be distinguished through orthonasal olfaction. Perceived odor differences did not always contribute to olfactory identification of fat content. Roasted beef and pork meats with higher fat content had more abundant fatty acids, aldehydes, and ketones. Phthalic acid, isobutyl 2-ropylpentyl ester, and carbon disulfide facilitated the olfactory discrimination of fat content in raw pork and beef samples. 2-Methyl-propanal, benzaldehyde, 1-hydroxy-2-propanone, 2,3-pentanedione, 2,5-octanedione, and 2-butanone contributed to odor differences of roasted beef samples differing in fat content. We conclude that beef and pork samples differing in fat content differ in volatile compound composition of the headspace, and that these differences facilitate discrimination between samples differing in fat content based on olfaction alone.


Assuntos
Carne de Porco , Carne Vermelha , Humanos , Animais , Bovinos , Suínos , Carne de Porco/análise , Olfato , Carne Vermelha/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Ácidos Graxos/análise
11.
Org Lett ; 25(48): 8739-8744, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38014913

RESUMO

A nickel-catalyzed chemoselective asymmetric transfer hydrogenation of α,ß-unsaturated ketimines using ethanol as a hydrogen donor under mild conditions that avoid using high-pressure hydrogen gas was developed. With this catalyst, C1-selective deuterated chiral allylic amines were efficiently synthesized using only stoichiometric 2-propanol-d8. Mechanism studies demonstrated the formation of a nickel hydride intermediate.

12.
Front Bioeng Biotechnol ; 11: 1278601, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38026887

RESUMO

Sansanmycins represent a family of uridyl peptide antibiotics with antimicrobial activity specifically against Mycobacterium tuberculosis (including drug-resistant M. tuberculosis) and Pseudomonas aeruginosa. They target translocase I (MraY) to inhibit bacterial cell wall assembly. Given the unique mechanism of action, sansanmycin has emerged as a potential lead compound for developing new anti-tuberculosis drugs, while the 5'-aminouridine moiety plays a crucial role in the pharmacophore of sansanmycin. For expanding the structural diversity of the 5'-aminouridine moiety of sansanmycin through biosynthetic methods, we firstly demonstrated that SsaM and SsaK are responsible for the biosynthesis of the 5'-aminouridine moiety of sansanmycin in vivo. Using the ssaK deletion mutant (SS/KKO), we efficiently obtained a series of new analogues with modified 5'-aminouridine moieties through mutational biosynthesis. Based on molecular networking analysis of MS/MS, twenty-two new analogues (SS-KK-1 to -13 and SS-KK-A to -I) were identified. Among them, four new analogues (SS-KK-1 to -3 and SS-KK-C) were purified and bioassayed. SS-KK-2 showed better antibacterial activity against E. coli ΔtolC than the parent compound sansanmycin A. SS-KK-3 showed the same anti-TB activity as sansanmycin A against M. tuberculosis H37Rv as well as clinically isolated, drug-sensitive and multidrug-resistant M. tuberculosis strains. Furthermore, SS-KK-3 exhibited significantly improved structural stability compared to sansanmycin A. The results suggested that mutasynthesis is an effective and practical strategy for expanding the structural diversity of 5'-aminouridine moiety in sansanmycin.

13.
Water Sci Technol ; 88(8): 2081-2107, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37906460

RESUMO

Thermal desalination evaporation of high-salt wastewater has been widely used in industry because of the proposed concept of 'zero liquid discharge'. However, due to the high content of Ca2+ and Mg2+ in high-salt wastewater, the heat exchanger, as the main treatment equipment, suffers from serious scaling problems. This review presents descaling and scale inhibition technologies of high-salt wastewater. The advantages and disadvantages of various technologies are summarized and analyzed to provide theoretical support for the research of descaling and anti-scaling of heat exchangers with high-salt wastewater. In future industrial development, the synergistic application of electromagnetic water treatment technology and scale inhibitors can significantly improve the anti-scaling effect, which can reach over 95% stably. Furthermore, the addition of a physical field can also expand the application range of scale inhibitors.


Assuntos
Águas Residuárias , Purificação da Água , Temperatura Alta , Cloreto de Sódio
14.
Elife ; 122023 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-37697742

RESUMO

Profound congenital sensorineural hearing loss (SNHL) prevents children from developing spoken language. Cochlear implantation and auditory brainstem implantation can provide partial hearing sensation, but language development outcomes can vary, particularly for patients with inner ear malformations and/or cochlear nerve deficiency (IEM&CND). Currently, the peripheral auditory structure is evaluated through visual inspection of clinical imaging, but this method is insufficient for surgical planning and prognosis. The central auditory pathway is also challenging to examine in vivo due to its delicate subcortical structures. Previous attempts to locate subcortical auditory nuclei using fMRI responses to sounds are not applicable to patients with profound hearing loss as no auditory brainstem responses can be detected in these individuals, making it impossible to capture corresponding blood oxygen signals in fMRI. In this study, we developed a new pipeline for mapping the auditory pathway using structural and diffusional MRI. We used a fixel-based approach to investigate the structural development of the auditory-language network for profound SNHL children with normal peripheral structure and those with IEM&CND under 6 years old. Our findings indicate that the language pathway is more sensitive to peripheral auditory condition than the central auditory pathway, highlighting the importance of early intervention for profound SNHL children to provide timely speech inputs. We also propose a comprehensive pre-surgical evaluation extending from the cochlea to the auditory-language network, showing significant correlations between age, gender, Cn.VIII median contrast value, and the language network with post-implant qualitative outcomes.


Assuntos
Perda Auditiva Neurossensorial , Humanos , Criança , Perda Auditiva Neurossensorial/diagnóstico por imagem , Idioma , Audição , Cóclea , Nervo Coclear/diagnóstico por imagem
15.
Sensors (Basel) ; 23(17)2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37687925

RESUMO

Accurate prediction of solar irradiance holds significant value for renewable energy usage and power grid management. However, traditional forecasting methods often overlook the time dependence of solar irradiance sequences and the varying importance of different influencing factors. To address this issue, this study proposes a dual-path information fusion and twin attention-driven solar irradiance forecasting model. The proposed framework comprises three components: a residual attention temporal convolution block (RACB), a dual-path information fusion module (DIFM), and a twin self-attention module (TSAM). These components collectively enhance the performance of multi-step solar irradiance forecasting. First, the RACB is designed to enable the network to adaptively learn important features while suppressing irrelevant ones. Second, the DIFM is implemented to reinforce the model's robustness against input data variations and integrate multi-scale features. Lastly, the TSAM is introduced to extract long-term temporal dependencies from the sequence and facilitate multi-step prediction. In the solar irradiance forecasting experiments, the proposed model is compared with six benchmark models across four datasets. In the one-step predictions, the average performance metrics RMSE, MAE, and MAPE of the four datasets decreased within the ranges of 0.463-2.390 W/m2, 0.439-2.005 W/m2, and 1.3-9.2%, respectively. Additionally, the average R2 value across the four datasets increased by 0.008 to 0.059. The experimental results indicate that the model proposed in this study exhibits enhanced accuracy and robustness in predictive performance, making it a reliable alternative for solar irradiance forecasting.

16.
ISA Trans ; 142: 289-298, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37574419

RESUMO

This paper proposes an event-based adaptive tracking control scheme for the n-link robotic systems in the presence of unknown backlash-like hysteresis (BLH) and deferred position constraints. By combining a transformation error with an asymmetric Lyapunov function, the devised control tactic achieves that the position constraints of robotic systems are not violated after user pre-specified time. In contrast to the results of robotic systems with position constraints, this paper removes a common assumption condition generated by the conventional barrier Lyapunov function method. Then, the adverse effect of unknown BLH can be offset by the Nussbaum function. Meanwhile, an event-triggered mechanism is designed to economize on the network bandwidth resources. Finally, based on the Lyapunov theory, an event-based adaptive tracking control tactic is proposed to ensure that all the signals of robotic systems are bounded under unknown BLH and deferred position constraints. Some simulation results proof that the devised control scheme is valid.

17.
iScience ; 26(9): 107509, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37636035

RESUMO

Long-term exposure to hyperoxia can leading to the bronchopulmonary dysplasia (BPD). The progression of BPD is primarily driven by the apoptosis of alveolar epithelial cells, and the regulation of autophagy has an impact on apoptosis. This study aims to investigate the therapeutic potential and underlying mechanism of an autophagy-promoting peptide (Tat-P) in ameliorating BPD. In vitro experiments demonstrated that Tat-P promoted autophagy and partially prevented apoptosis caused by exposure to hyperoxia. Further investigation into the mechanism revealed that Tat-P competitively binds to GAPR1, displacing the Beclin1 protein and thereby inhibiting the apoptosis. In vivo experiments conducted on Sprague-Dawley pups exposed to high oxygen levels demonstrated that Tat-P promoted autophagy and reduced apoptosis in lung tissues and ameliorated BPD-related phenotypes. Our findings elucidate the underlying mechanisms and effects of Tat-P in enhancing autophagy and preventing apoptosis. This study presents an approach for the prevention and treatment of BPD.

18.
JBMR Plus ; 7(8): e10777, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37614298

RESUMO

Preptin is derived from the cleavage of the E-peptide of pro-insulin-like growth factor (IGF)-II and is an insulin secretagogue. Observational studies have linked elevated circulating preptin to metabolic dysfunction in humans; however, a causal role for preptin in metabolic dysfunction has not been established. Additionally, preptin can promote osteoblast proliferation and differentiation, suggesting a link with skeletal health. We previously described a global preptin knockout (KO) model. In this study, we sought to uncover the impact of preptin KO in mice on the response to a moderately high-fat diet (HFD) and low-fat diet (LFD). HFD groups had higher weight and fat mass gain, lower trabecular and cortical bone volume and fracture load, and higher liver triglycerides. In males, preptin deficiency led to lower blood glucose than wild-type (WT) mice under LFD conditions. This was accompanied by differences in bone microarchitecture, including lower trabecular bone volume fraction, trabecular number, and lower cortical thickness. These differences were absent in female mice, although KO females had a HFD-driven increase in fat mass and liver triglycerides that was absent in WT mice. Female WT mice had increased glucose-stimulated insulin secretion under HFD conditions that was absent in female KO mice. Overall, preptin may have a detrimental impact on metabolism and a positive impact on bone health in male mice and may protect against liver fat storage in females while enabling islet compensation under HFD conditions. When we consider that serum preptin levels are elevated in humans of both sexes in pathological states in which insulin levels are elevated, the impact of preptin on comorbidity risk needs to be better understood. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

19.
Heliyon ; 9(8): e18708, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37554782

RESUMO

Background: Ovarian serous cystadenocarcinoma (OSC) is the most prevalent histological subtype of ovarian cancer (OV) and presents a serious threat to women's health. Anoikis is an essential component of metastasis, and tumor cells can get beyond it to become viable. The impact of anoikis on OSC, however, has only been the topic of a few studies. Methods: The mRNA sequencing and clinical information of OSC came from The Cancer Genome Atlas Target Genotype-Tissue Expression (TCGA TARGET GTEx) dataset. Anoikis-related genes (ARGs) were collected by Harmonizome and GeneCards websites. Centered on these ARGs, we used unsupervised consensus clustering to explore potential tumor typing and filtered hub ARGs to create a model of predictive signature for OSC patients. Furthermore, we presented clinical specialists with a novel nomogram based on ARGs, revealing the underlying clinical relevance of this signature. Finally, we explored the immune microenvironment among various risk groups. Results: We identified 24 ARGs associated with the prognosis of OSC and classified OSC patients into three subtypes, and the subtype with the best prognosis was more enriched in immune-related pathways. Seven ARGs (ARHGEF7, NOTCH4, CASP2, SKP2, PAK4, LCK, CCDC80) were chosen to establish a risk model and a nomogram that can provide practical clinical decision support. Risk scores were found to be an independent and significant prognostic factor in OSC patients. The CIBERSORTx result revealed an inflammatory microenvironment is different for risk groups, and the proportion of immune infiltrates of Macrophages M1 is negatively correlated with risk score (rs = -0.21, P < 0.05). Ultimately, quantitative reverse transcription polymerase chain reaction (RT-PCR) was utilized to validate the expression of the seven pivotal ARGs. Conclusion: In this study, based on seven ARGs, a risk model and nomogram established can be used for risk stratification and prediction of survival outcomes in patients with OSC, providing a reliable reference for individualized therapy of OSC patients.

20.
Int J Gen Med ; 16: 2897-2921, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37457751

RESUMO

Background: Endometriosis, a common gynecological condition, can cause symptoms such as dysmenorrhea, infertility, and abnormal bleeding, which can negatively affect a woman's quality of life. In the current study, the pathophysiological mechanisms of endometriosis are unknown, but this study suggests that endometriosis is associated with dysregulation of the autoimmune system. This study identify hub genes involved in the prevalence, identification and diagnostic value of endometriosis and autoimmune diseases, and explore the central genes and immune infiltrates, the diagnosis of endometriosis provides a new sight of thinking about diagnosis and treatment. Methods and Results: The relevant datasets for endometriosis GSE141549, GSE7305 and autoimmune disease-related genes (AIDGs) were downloaded from online database. Using the "limma" package and WGCNA to screen out the autoimmune disease related genes and endometriosis related genes, the autoimmune disease gene-related differential genes (AID-DEGs) progressive GO, KEGG enrichment analysis, and then using the protein interaction network and Cytoscape software to select hub genes (CXCL12, PECAM1, NGF, CTGF, WNT5A), using the "pROC" package to analyze the hub genes for the diagnostic value of endometriosis. The difference in the importance of hub genes for the diagnosis of endometriosis was analyzed by machine learning random forest, and the combined diagnostic value of hub genes was analyzed by using the Support Vector Machine (SVM) algorithm. The eutopic (EU) and ectopic endometrium (EC) immune microenvironment of endometriosis was evaluated using CIBERSORT, the correlation of hub genes to the immune microenvironment was analyzed. Conclusion: The hub genes associated with AIDGs are differentially expressed in EC and EU of endometriosis and possess important value for the diagnosis of endometriosis. The hub genes have a very important impact on the immune microenvironment of endometriosis, which is important for exploring the connection between endometriosis and autoimmune diseases and provides a new insight for the subsequent study of immunotherapy and diagnosis of endometriosis.

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