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1.
Neural Netw ; 176: 106339, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38703420

RESUMO

Malaria is a significant health concern worldwide, particularly in Africa where its prevalence is still alarmingly high. Using artificial intelligence algorithms to diagnose cells with malaria provides great convenience for clinicians. In this paper, a densely connected convolutional dynamic learning network (DCDLN) is proposed for the diagnosis of malaria disease. Specifically, after data processing and partitioning of the dataset, the densely connected block is trained as a feature extractor. To classify the features extracted by the feature extractor, a classifier based on a dynamic learning network is proposed in this paper. Based on experimental results, the proposed DCDLN method demonstrates a diagnostic accuracy rate of 97.23%, surpassing the diagnostic performance than existing advanced methods on an open malaria cell dataset. This accurate diagnostic effect provides convincing evidence for clinicians to make a correct diagnosis. In addition, to validate the superiority and generalization capability of the DCDLN algorithm, we also applied the algorithm to the skin cancer and garbage classification datasets. DCDLN achieved good results on these datasets as well, demonstrating that the DCDLN algorithm possesses superiority and strong generalization performance.

2.
Aging Dis ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38739940

RESUMO

Programmed cell death is pivotal for several physiological processes, including immune defense. Further, it has been implicated in the pathogenesis of developmental disorders and the onset of numerous diseases. Multiple modes of programmed cell death, including apoptosis, pyroptosis, necroptosis, and ferroptosis, have been identified, each with their own unique characteristics and biological implications. In February 2023, Liu Xiaoguang and his team discovered "disulfidptosis," a novel pathway of programmed cell death. Their findings demonstrated that disulfidptosis is triggered in glucose-starved cells exhibiting high expression of a protein called SLC7A11. Furthermore, disulfidptosis is marked by a drastic imbalance in the NADPH/NADP+ ratio and the abnormal accumulation of disulfides like cystine. These changes ultimately lead to the destabilization of the F-actin network, causing cell death. Given that high SLC7A11 expression is a key feature of certain cancers, these findings indicate that disulfidptosis could serve as the basis of innovative anti-cancer therapies. Hence, this review delves into the discovery of disulfidptosis, its underlying molecular mechanisms and metabolic regulation, and its prospective applications in disease treatment.

3.
Signal Transduct Target Ther ; 9(1): 88, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38594257

RESUMO

G protein-coupled receptors (GPCRs), the largest family of human membrane proteins and an important class of drug targets, play a role in maintaining numerous physiological processes. Agonist or antagonist, orthosteric effects or allosteric effects, and biased signaling or balanced signaling, characterize the complexity of GPCR dynamic features. In this study, we first review the structural advancements, activation mechanisms, and functional diversity of GPCRs. We then focus on GPCR drug discovery by revealing the detailed drug-target interactions and the underlying mechanisms of orthosteric drugs approved by the US Food and Drug Administration in the past five years. Particularly, an up-to-date analysis is performed on available GPCR structures complexed with synthetic small-molecule allosteric modulators to elucidate key receptor-ligand interactions and allosteric mechanisms. Finally, we highlight how the widespread GPCR-druggable allosteric sites can guide structure- or mechanism-based drug design and propose prospects of designing bitopic ligands for the future therapeutic potential of targeting this receptor family.


Assuntos
Descoberta de Drogas , Receptores Acoplados a Proteínas G , Estados Unidos , Humanos , Receptores Acoplados a Proteínas G/química , Sítio Alostérico , Desenho de Fármacos , Ligantes
4.
Asian J Pharm Sci ; 19(2): 100908, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38623486

RESUMO

The disulfide bond plays a crucial role in the design of anti-tumor prodrugs due to its exceptional tumor-specific redox responsiveness. However, premature breaking of disulfide bonds is triggered by small amounts of reducing substances (e.g., ascorbic acid, glutathione, uric acid and tea polyphenols) in the systemic circulation. This may lead to toxicity, particularly in oral prodrugs that require more frequent and high-dose treatments. Fine-tuning the activation kinetics of these prodrugs is a promising prospect for more efficient on-target cancer therapies. In this study, disulfide, steric disulfide, and ester bonds were used to bridge cabazitaxel (CTX) to an intestinal lymph vessel-directed triglyceride (TG) module. Then, synthetic prodrugs were efficiently incorporated into self-nanoemulsifying drug delivery system (corn oil and Maisine CC were used as the oil phase and Cremophor EL as the surfactant). All three prodrugs had excellent gastric stability and intestinal permeability. The oral bioavailability of the disulfide bond-based prodrugs (CTX-(C)S-(C)S-TG and CTX-S-S-TG) was 11.5- and 19.1-fold higher than that of the CTX solution, respectively, demonstrating good oral delivery efficiency. However, the excessive reduction sensitivity of the disulfide bond resulted in lower plasma stability and safety of CTX-S-S-TG than that of CTX-(C)S-(C)S-TG. Moreover, introducing steric hindrance into disulfide bonds could also modulate drug release and cytotoxicity, significantly improving the anti-tumor activity even compared to that of intravenous CTX solution at half dosage while minimizing off-target adverse effects. Our findings provide insights into the design and fine-tuning of different disulfide bond-based linkers, which may help identify oral prodrugs with more potent therapeutic efficacy and safety for cancer therapy.

5.
J Imaging ; 10(3)2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38535150

RESUMO

While Siamese object tracking has witnessed significant advancements, its hard real-time behaviour on embedded devices remains inadequately addressed. In many application cases, an embedded implementation should not only have a minimal execution latency, but this latency should ideally also have zero variance, i.e., be predictable. This study aims to address this issue by meticulously analysing real-time predictability across different components of a deep-learning-based video object tracking system. Our detailed experiments not only indicate the superiority of Field-Programmable Gate Array (FPGA) implementations in terms of hard real-time behaviour but also unveil important time predictability bottlenecks. We introduce dedicated hardware accelerators for key processes, focusing on depth-wise cross-correlation and padding operations, utilizing high-level synthesis (HLS). Implemented on a KV260 board, our enhanced tracker exhibits not only a speed up, with a factor of 6.6, in mean execution time but also significant improvements in hard real-time predictability by yielding 11 times less latency variation as compared to our baseline. A subsequent analysis of power consumption reveals our approach's contribution to enhanced power efficiency. These advancements underscore the crucial role of hardware acceleration in realizing time-predictable object tracking on embedded systems, setting new standards for future hardware-software co-design endeavours in this domain.

6.
Water Res ; 255: 121523, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38554632

RESUMO

The paddy field is a hot area of biogeochemical process. The paddy water has a large capacity in photo-generation of reactive intermediates (RIs) due to abundant photosensitive dissolved organic matter (DOM), which is influenced by the spatial heterogeneity of paddy soils but rarely been explored. Our work presents the first investigation of the role of soil properties on photochemistry in paddy water. Soil organic matter (SOM), determined by the temperature, was the dominant factor for the photo-generation of RIs in paddy water of main rice producing areas. The RI concentrations generated with abundant SOM from cool regions are 0.05-8.71 times higher than those for the warm regions in China. The humic-like substance and aromatic-like compounds of DOM plays an essential role in RIs generation, which is abundant in paddy soils rich in SOM from Chinese cool regions. In addition, RIs can efficiently accelerate the photo-ammonification of urea and free amino acids by 15.2 %-164 %, leading to 0.13-0.17 mmol/L/d photo-produced ammonium after fertilization, which is preferentially absorbed by rice. The findings of this study will extend our knowledge of the geochemistry of global paddy field ecosystem. The potential role of RIs in nitrogen cycle should be highlighted in the agroecosystem.

7.
Neurol Sci ; 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38499889

RESUMO

BACKGROUND: Parkinson's disease (PD) is viewed as a progressively deteriorating neurodegenerative disorder, the exact etiology of which remains not fully deciphered to this date. The gut microbiota could play a crucial role in PD development by modulating the human immune system. OBJECTIVE: This study aims to explore the relationship between gut microbiota and PD, focusing on how immune characteristics may both directly and indirectly influence their interaction. METHODS: Utilizing cumulative data from genome-wide association studies (GWAS), our research conducted a two-sample Mendelian randomization (MR) analysis to clarify the association between the gut microbiome and PD. Additionally, by employing a two-step MR approach, we assessed the impact of gut microbiota on PD development via immune characteristics and quantified HLA-DR mediation effect on plasmacytoid dendritic cells (pDCs). RESULTS: We discovered significant associations between PD and microbiota, comprising one class, one order, two families, and two genera. Furthermore, we explored the extent to which HLA-DR on pDCs mediates the effect of Butyrivibrio gut microbiota on PD. CONCLUSION: Our study emphasizes the complex interactions between the gut microbiota, immune characteristics, and PD. The relationships and intermediary roles identified in our research provide important insights for developing potential therapies that target the gut microbiome to alleviate symptoms in PD patients.

8.
J Exerc Sci Fit ; 22(2): 159-167, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38464602

RESUMO

Objectives: Due to the character of the taekwondo, the adenosine triphosphate-phosphocreatine system provides the energy for each kick, the glycolytic system supports the repeated execution of kicks, and the aerobic system promotes recovery between these movements and the bout. Therefore, taekwondo athletes require high explosive power and anaerobic capacity in order to carry out sustained and powerful attacks. So, the purpose of this study is to compare the effects of APRE and VBRT on lower-limb explosive power and anaerobic capacity in college taekwondo players. Methods: A total of 30 taekwondo players completed an 8-week training intervention with autoregulatory progressive resistance exercise (APRE; n = 15) and velocity-based resistance training (VBRT; n = 15). Testing included the one-repetition maximum squat, countermovement jump (CMJ), taekwondo anaerobic intermittent kick test (TAIKT), and 30-s Wingate anaerobic test (WAnT). Results: (1) Intragroup comparisons revealed significant effects for one-repetition maximum squat, peak power of CMJ (CMJPP), relative peak power of CMJ (CMJRPP), and total number of TAIKT (TAIKTTN) in both the APRE and VBRT groups. The VBRT group exhibited small effect sizes for time at peak power of WAnT (WAnTPPT) and moderate effect sizes for peak power of WAnT (WAnTPP), relative peak power of WAnT (WAnTRPP), and fatigue index of TAIKT (TAIKTFI), whereas the APRE group exhibited small effect sizes for TAIKTFI. (2) Intergroup comparisons revealed no significant effects in any of the results. However, VBRT demonstrated a moderate advantage in WAnTPP and WAnTRPP, whereas APRE had a small advantage in CMJPP and CMJRPP. Conclusions: These findings suggest that APRE improved explosive power (CMJPP and CMJRPP) more, whereas VBRT improved anaerobic power output (WAnTPP and WAnTRPP) more. Both methods were found to have similar effects in improving the anaerobic endurance (WAnTPPT and TAIKTTN) and fatigue index (power drop of WAnT and TAIKTFI).

9.
Glob Chang Biol ; 30(1): e17138, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38273499

RESUMO

Water availability (WA) is a key factor influencing the carbon cycle of terrestrial ecosystems under climate warming, but its effects on gross primary production (EWA-GPP ) at multiple time scales are poorly understood. We used ensemble empirical mode decomposition (EEMD) and partial correlation analysis to assess the WA-GPP relationship (RWA-GPP ) at different time scales, and geographically weighted regression (GWR) to analyze their temporal dynamics from 1982 to 2018 with multiple GPP datasets, including near-infrared radiance of vegetation GPP, FLUXCOM GPP, and eddy covariance-light-use efficiency GPP. We found that the 3- and 7-year time scales dominated global WA variability (61.18% and 11.95%), followed by the 17- and 40-year time scales (7.28% and 8.23%). The long-term trend also influenced 10.83% of the regions, mainly in humid areas. We found consistent spatiotemporal patterns of the EWA-GPP and RWA-GPP with different source products: In high-latitude regions, RWA-GPP changed from negative to positive as the time scale increased, while the opposite occurred in mid-low latitudes. Forests had weak RWA-GPP at all time scales, shrublands showed negative RWA-GPP at long time scales, and grassland (GL) showed a positive RWA-GPP at short time scales. Globally, the EWA-GPP , whether positive or negative, enhanced significantly at 3-, 7-, and 17-year time scales. For arid and humid zones, the semi-arid and sub-humid zones experienced a faster increase in the positive EWA-GPP , whereas the humid zones experienced a faster increase in the negative EWA-GPP . At the ecosystem types, the positive EWA-GPP at a 3-year time scale increased faster in GL, deciduous broadleaf forest, and savanna (SA), whereas the negative EWA-GPP at other time scales increased faster in evergreen needleleaf forest, woody savannas, and SA. Our study reveals the complex and dynamic EWA-GPP at multiple time scales, which provides a new perspective for understanding the responses of terrestrial ecosystems to climate change.


Assuntos
Ecossistema , Água , Florestas , Ciclo do Carbono , Mudança Climática
10.
J Strength Cond Res ; 38(4): 656-670, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38048589

RESUMO

ABSTRACT: Zhang, M, Chen, L, Dai, J, Yang, Q, Huang, Z, He, J, Ji, H, Sun, J, and Li, D. Application of a new monitoring variable: Effects of power loss during squat training on strength gains and sports performance. J Strength Cond Res 38(4): 656-670, 2024-This study aimed to compare the effects of power loss (PL) autoregulated volume (PL10 and PL20) with standardized fixed-load (FL) prescription on strength, sports performance, and lean body mass (LBM). Thirty-five female basketball players from a sports college were randomly assigned to 3 experimental groups (PL10, n = 12; PL20, n = 12; and FL, n = 11, respectively) that performed a resistance training (RT) program with wave-like periodization for 10 weeks using the back squat exercise. Assessments performed before (Pre) and after (Post) intervention included assessed 1 repetition maximum (1RM), body composition, 20-m sprint (T20M), change of direction (COD), and jump performance, including countermovement jump with arm swing, maximum vertical jump, and reactive strength index. Three groups showed significant improvements in strength (effect size [ES]: PL10 = 2.98, PL20 = 3.14, and FL = 1.90; p < 0.001) and jump performance (ES: PL10 = 0.74, PL20 = 1.50, and FL = 0.50; p <0.05-0.001). However, PL10 and PL20 demonstrated different advantages in sports performance compared with FL (group × time interaction, p <0.05). Specifically, PL10 significantly improved COD performance (ES = -0.79 ∼ -0.53, p <0.01), whereas PL20 showed greater improvements in sprint (ES = -0.57, p <0.05) and jump performance (ES = 0.67-1.64, p <0.01-0.001). Moreover, PL10 resulted in similar gains to PL20 and beneficial improvements compared with FL in LBM, despite performing the least repetitions. Overall, the study indicates that power loss-based autoregulation induces greater gains in LBM and sports performance, as well as eliciting a higher efficiency dose response than standardized FL prescriptions, particularly for PL10. Therefore, incorporating PL monitoring in training programs is recommended, and further studies on power-based RT would be worthwhile.


Assuntos
Desempenho Atlético , Basquetebol , Treinamento Resistido , Humanos , Feminino , Força Muscular/fisiologia , Desempenho Atlético/fisiologia , Treinamento Resistido/métodos , Composição Corporal
11.
Nucleic Acids Res ; 52(D1): D376-D383, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37870448

RESUMO

Allosteric regulation, induced by perturbations at an allosteric site topographically distinct from the orthosteric site, is one of the most direct and efficient ways to fine-tune macromolecular function. The Allosteric Database (ASD; accessible online at http://mdl.shsmu.edu.cn/ASD) has been systematically developed since 2009 to provide comprehensive information on allosteric regulation. In recent years, allostery has seen sustained growth and wide-ranging applications in life sciences, from basic research to new therapeutics development, while also elucidating emerging obstacles across allosteric research stages. To overcome these challenges and maintain high-quality data center services, novel features were curated in the ASD2023 update: (i) 66 589 potential allosteric sites, covering > 80% of the human proteome and constituting the human allosteric pocketome; (ii) 748 allosteric protein-protein interaction (PPI) modulators with clear mechanisms, aiding protein machine studies and PPI-targeted drug discovery; (iii) 'Allosteric Hit-to-Lead,' a pioneering dataset providing panoramic views from 87 well-defined allosteric hits to 6565 leads and (iv) 456 dualsteric modulators for exploring the simultaneous regulation of allosteric and orthosteric sites. Meanwhile, ASD2023 maintains a significant growth of foundational allosteric data. Based on these efforts, the allosteric knowledgebase is progressively evolving towards an integrated landscape, facilitating advancements in allosteric target identification, mechanistic exploration and drug discovery.


Assuntos
Sítio Alostérico , Bases de Conhecimento , Humanos , Regulação Alostérica , Descoberta de Drogas , Ligantes , Proteoma , Mapas de Interação de Proteínas
12.
Neural Regen Res ; 19(8): 1696-1701, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38103234

RESUMO

Brain homeostasis refers to the normal working state of the brain in a certain period, which is important for overall health and normal life activities. Currently, there is a lack of effective treatment methods for the adverse consequences caused by brain homeostasis imbalance. Snapin is a protein that assists in the formation of neuronal synapses and plays a crucial role in the normal growth and development of synapses. Recently, many researchers have reported the association between snapin and neurologic and psychiatric disorders, demonstrating that snapin can improve brain homeostasis. Clinical manifestations of brain disease often involve imbalances in brain homeostasis and may lead to neurological and behavioral sequelae. This article aims to explore the role of snapin in restoring brain homeostasis after injury or diseases, highlighting its significance in maintaining brain homeostasis and treating brain diseases. Additionally, it comprehensively discusses the implications of snapin in other extracerebral diseases such as diabetes and viral infections, with the objective of determining the clinical potential of snapin in maintaining brain homeostasis.

13.
Patient Prefer Adherence ; 17: 3421-3433, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38111691

RESUMO

Purpose: We assess whether the sequential mediating effects of self-efficacy and depressive symptoms on the relationship between community efficacy for non-communicable disease management (COEN) and medication adherence and whether these relationships differed by sex and age. Patients and Methods: Overall, 662 individuals from 12 communities in China were interviewed twice 1 year apart. Serial mediation analysis examined whether the relationship between COEN and medication adherence was mediated by self-efficacy and depressive symptoms. Model invariance across sex and age groups was assessed using multi-group analysis. Results: Serial mediation analysis indicated that self-efficacy and depressive symptoms sequentially mediated relationship between COEN and medication adherence. Multi-group analysis by sex showed that the path from self-efficacy to medication adherence was significant only for females and from depressive symptoms to medication adherence was significant only for males. Conclusion: Interventions that enhance individual self-efficacy may be beneficial in decreasing depressive symptoms and improving medication adherence.

14.
Chem Soc Rev ; 52(24): 8651-8677, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-37990599

RESUMO

Traditionally, drugs are monovalent, targeting only one site on the protein surface. This includes orthosteric and allosteric drugs, which bind the protein at orthosteric and allosteric sites, respectively. Orthosteric drugs are good in potency, whereas allosteric drugs have better selectivity and are solutions to classically undruggable targets. However, it would be difficult to simultaneously reach high potency and selectivity when targeting only one site. Also, both kinds of monovalent drugs suffer from mutation-caused drug resistance. To overcome these obstacles, dualsteric modulators have been proposed in the past twenty years. Compared to orthosteric or allosteric drugs, dualsteric modulators are bivalent (or bitopic) with two pharmacophores. Each of the two pharmacophores bind the protein at the orthosteric and an allosteric site, which could bring the modulator with special properties beyond monovalent drugs. In this study, we comprehensively review the current development of dualsteric modulators. Our main effort reason and illustrate the aims to apply the dualsteric approach, including a "double win" of potency and selectivity, overcoming mutation-caused drug resistance, developments of function-biased modulators, and design of partial agonists. Moreover, the strengths of the dualsteric technique also led to its application outside pharmacy, including the design of highly sensitive fluorescent tracers and usage as molecular rulers. Besides, we also introduced drug targets, designing strategies, and validation methods of dualsteric modulators. Finally, we detail the conclusions and perspectives.


Assuntos
Ligantes , Sítio Alostérico , Mutação , Regulação Alostérica
15.
Front Immunol ; 14: 1236444, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37841237

RESUMO

Introduction: Lung squamous cell carcinoma (LUSC) is a unique subform of nonsmall cell lung cancer (NSCLC). The lack of specific driver genes as therapeutic targets leads to worse prognoses in patients with LUSC, even with chemotherapy, radiotherapy, or immune checkpoint inhibitors. Furthermore, research on the LUSC-specific prognosis genes is lacking. This study aimed to develop a comprehensive LUSC-specific differentially expressed genes (DEGs) signature for prognosis correlated with tumor progression, immune infiltration,and stem index. Methods: RNA sequencing data for LUSC and lung adenocarcinoma (LUAD) were extracted from The Cancer Genome Atlas (TCGA) data portal, and DEGs analyses were conducted in TCGA-LUSC and TCGA-LUAD cohorts to identify specific DEGs associated with LUSC. Functional analysis and protein-protein interaction network were performed to annotate the roles of LUSC-specific DEGs and select the top 100 LUSC-specific DEGs. Univariate Cox regression and least absolute shrinkage and selection operator regression analyses were performed to select prognosis-related DEGs. Results: Overall, 1,604 LUSC-specific DEGs were obtained, and a validated seven-gene signature was constructed comprising FGG, C3, FGA, JUN, CST3, CPSF4, and HIST1H2BH. FGG, C3, FGA, JUN, and CST3 were correlated with poor LUSC prognosis, whereas CPSF4 and HIST1H2BH were potential positive prognosis markers in patients with LUSC. Receiver operating characteristic analysis further confirmed that the genetic profile could accurately estimate the overall survival of LUSC patients. Analysis of immune infiltration demonstrated that the high risk (HR) LUSC patients exhibited accelerated tumor infiltration, relative to low risk (LR) LUSC patients. Molecular expressions of immune checkpoint genes differed significantly between the HR and LR cohorts. A ceRNA network containing 19 lncRNAs, 50 miRNAs, and 7 prognostic DEGs was constructed to demonstrate the prognostic value of novel biomarkers of LUSC-specific DEGs based on tumor progression, stemindex, and immune infiltration. In vitro experimental models confirmed that LUSC-specific DEG FGG expression was significantly higher in tumor cells and correlated with immune tumor progression, immune infiltration, and stem index. In vitro experimental models confirmed that LUSC-specific DEG FGG expression was significantly higher in tumor cells and correlated with immune tumor progression, immune infiltration, and stem index. Conclusion: Our study demonstrated the potential clinical implication of the 7- DEGs signature for prognosis prediction of LUSC patients based on tumor progression, immune infiltration, and stem index. And the FGG could be an independent prognostic biomarker of LUSC promoting cell proliferation, migration, invasion, THP-1 cell infiltration, and stem cell maintenance.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Prognóstico , Neoplasias Pulmonares/genética , Carcinoma de Células Escamosas/genética , Histonas , Pulmão
16.
Drug Discov Today ; 28(12): 103803, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37852356

RESUMO

G-protein-coupled receptors (GPCRs) are a family of cell surface proteins that can sense a variety of extracellular stimuli and mediate multiple signaling transduction pathways involved in human physiology. Recent advances in GPCR structural biology have revealed a relatively conserved intracellular allosteric site in multiple GPCRs, which can be utilized to modulate receptors from the inside. This novel intracellular site partially overlaps with the G-protein and ß-arrestin coupling sites, providing a novel avenue for biological intervention. Here, we review evidence available for GPCR structures complexed with intracellular small-molecule allosteric modulators, elucidating drug-target interactions and allosteric mechanisms. Moreover, we highlight the potential of intracellular allosteric modulators in achieving biased signaling, which provides insights into biased allosteric mechanisms.


Assuntos
Descoberta de Drogas , Receptores Acoplados a Proteínas G , Humanos , Sítio Alostérico , Regulação Alostérica , Ligantes , Receptores Acoplados a Proteínas G/metabolismo
17.
ACS Omega ; 8(34): 30888-30897, 2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37663496

RESUMO

Photo-cross-linkable hydrogels have recently gained increased interest in the field of biomedical applications. In this study, silk fibroin was derivatized with methacrylic anhydride (MA) to obtain silk fibroin methacryloyl (SFMA), forming hydrogel under UV light exposure in 1 min. The SFMA sol-gel transition did not involve significant structural change at the early stage. Then, the formation of the irreversible ß-sheet was confirmed after 24 h. The resulting SFMA hydrogel showed a homogeneous porous structure with pore sizes ranging from 400 to 700 µm, depending on the content. In addition, these hydrogels demonstrated a lower swelling capacity, higher rheological properties and compressive modulus, and slow degradation behavior at higher content, likely due to the higher degree of cross-linking. An experiment with cells indicated the good cell compatibility of these hydrogels, as revealed by Cell Counting Kit-8 (CCK-8) assays. As a tissue-engineered material, this photo-cross-linkable SFMA is expected to have a wide range of applications in the biomedical field.

18.
Artigo em Inglês | MEDLINE | ID: mdl-37667115

RESUMO

Maritime transport plays a crucial role in international trade. As the number and tonnage of ships continue to increase, traditional shipping routes are becoming progressively congested. The development of Arctic shipping routes has the potential to significantly improve trade efficiency and decrease reliance on traditional shipping routes. At the same time, the harsh navigation conditions in the Arctic pose a huge challenge to ships crossing the Arctic shipping routes. To address the above issues, this paper reviews the natural, navigational environment and unique navigational modes of ships in the Arctic shipping routes. Furthermore, the navigational risks caused by factors including low temperature, sea ice, poor visibility, communication, lack of infrastructure, lack of navigational experience, lack of historical data, high collision risk, and complex navigational environment are summarized and analyzed, providing a reference for researchers and policymakers to conduct research related to Arctic shipping routes.

19.
Front Neurosci ; 17: 1221990, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37600015

RESUMO

Background: Existing evidence on the association between sedentary behavior (SB) and cognitive function remains inconclusive. Therefore, this study investigated the association between SB and the risk of cognitive decline (CD) or mild cognitive impairment (MCI) in the elderly. Methods: A comprehensive search was independently conducted by two researchers (XC and GQ) in seven electronic databases, including Medline (via PubMed), China Biology Medicine, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang database, and VIP database for Chinese technical periodicals, covering studies published from the inception of database to June 2023. Studies that investigated the relationship between SB and the risk of CD or MCI in the elderly were included. The quality of the literature was assessed using the Newcastle-Ottawa Scale (NOS) and the Agency for Healthcare Research and Quality (AHRQ) assessment tools. The combined effect size analysis, subgroup analysis, and publication bias assessment were performed using STATA 14.0. Results: A total of 13 cross-sectional and 6 cohort studies involving 81,791 individuals were included, comprising 17 high-quality studies and 2 medium-quality studies. We found that SB was significantly associated with an increased risk of CD [odds ratio (OR) = 1.69, 95% confidence intervals (CI): 1.47-1.94] or MCI (OR = 1.34, 95% CI: 1.14-1.56) among the elderly. Subgroup analysis stratified according to comorbidity, lifestyle, family structure, publication year, and region showed statistical differences between groups, and the consistency of the results revealed the sources of the heterogeneity. Conclusion: This meta-analysis showed that SB is positively associated with the risk of CD or MCI in the elderly, providing a higher level of evidence for the promotion of healthy behaviors by clinicians and health policymakers. Due to the number and quality of the included articles, more high-quality longitudinal studies are needed to further confirm our findings.

20.
Heliyon ; 9(8): e18178, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37576293

RESUMO

Animals exhibit different extents of sexual dimorphism in a variety of phenotypes. Sex differences in longevity, one of the most complex life history traits, have also been reported. Although lifespan regulation has been studied extensively in the fruit fly, Drosophila melanogaster, the sex differences in lifespan have not been consistent in previous studies. To explore this issue, we revisited this question by examining the lifespan and stress resistance of both sexes among 15 inbred strains. We first found positive correlations between males and females from the same strain in terms of lifespan and resistance to starvation and desiccation stress. Although the lifespan difference between male and female flies varied greatly depending on the strain, males across all strains collectively had a longer lifespan. In contrast, females showed better resistance to starvation and desiccation stress. We also observed greater variation in lifespan and resistance to starvation and desiccation stress in females. Unexpectedly, there was no notable correlation observed between lifespan and the three types of stress resistance in either males or females. Overall, our study provides new data regarding sexual dimorphism in fly lifespan and stress resistance; this information may promote the investigation of mechanisms underlying longevity in future research.

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