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Exosomes derived from mesenchymal stem cells (MSCs) have been confirmed to enhance cell proliferation and improve tissue repair. Exosomes release their contents into the cytoplasmic solution of the recipient cell to mediate cell expression, which is the main pathway through which exosomes exert therapeutic effects. The corresponding process of exosome internalization mainly occurs in the early stage of treatment. However, the therapeutic effect of exosomes in the early stage remains to be further studied. We report that the three-dimensional cell traction force can intuitively reflect the ability of exosomes to enhance the cytoskeleton and cell contractility of recipient cells, serving as an effective method to characterize the therapeutic effect of exosomes. Compared with traditional biochemical methods, we can visualize the early therapeutic effect of exosomes in real time without damage by quantifying the cell traction force. Through quantitative analysis of traction forces, we found that endometrial stromal cells exhibit short-term cell roundness accompanied by greater traction force during the early stage of exosome therapy. Further experiments revealed that exosomes enhance the traction force and cytoskeleton by regulating the Rac1/RhoA signaling pathway, thereby promoting cell proliferation. This work provides an effective method for rapidly quantifying the therapeutic effects of exosomes and studying the underlying mechanisms involved.
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Solid-state spin systems with nitrogen-vacancy (NV) centers in diamonds constitute an increasingly popular platform for quantum sensing. However, most existing platforms designed with ensemble NV centers exhibit a sensitivity that is significantly less than the theoretical maximum. This low sensitivity limits the expansion of the experimental results and application areas. In this study, the sensitivity is improved by increasing the pumping depth of the excitation beam to increase the number of particles involved in spin polarization at a given laser intensity. Compared with the proposed Airy beam with a long focal depth (25.46 λ) and the widely utilized Gauss beam pumping ensemble NV centers, the spin resonance factor fSR can be improved by 10.02%. This sensitivity-optimized approach enhances the functionality of sensors with NV centers.
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Background: Quantitative detection of glucose-6-phosphate dehydrogenase (G6PD) is commonly done to screen for G6PD deficiency. However, current reference intervals (RIs) of G6PD are unsuitable for evaluating G6PD-activity levels with local populations or associating G6PD variants with hemolysis risk to aid clinical decision-making. We explored appropriate RIs and clinical decision limits (CDLs) for G6PD activity in individuals from Guangzhou, China. Methods: We enrolled 5,852 unrelated individuals between 2020 and 2022 and screened their samples in quantitative assays for G6PD activity. We conducted further investigations, including G6PD genotyping, thalassemia genotyping, follow-up analysis, and statistical analysis, for different groups. Results: In Guangzhou, the RIs for the G6PD activities were 11.20-20.04 U/g Hb in male and 12.29-23.16 U/g Hb in female. The adjusted male median and normal male median (NMM) values were 15.47 U/g Hb and 15.51 U/g Hb, respectively. A threshold of 45% of the NMM could be used as a CDL to estimate the probability of G6PD variants. Our results revealed high hemolysis-risk CDLs (male: <10% of the NMM, female: <30% of the NMM), medium hemolysis-risk CDLs (male: 10%-45% of the NMM, female: 30%-79% of the NMM), and low hemolysis-risk CDLs (male: ≥ 45% of the NMM, female: ≥ 79% of the NMM). Conclusions: Collectively, our findings contribute to a more accurate evaluation of G6PD-activity levels within the local population and provide valuable insights for clinical decision-making. Specifically, identifying threshold values for G6PD variants and hemolysis risk enables improved prediction and management of G6PD deficiency, ultimately enhancing patient care and treatment outcomes.
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Objective: To analyze the CT and MR features of Primary hepatic neuroendocrine neoplasms (PHNENs) in order to enhance the diagnostic accuracy of this disease. Methods: A retrospective analysis was conducted on patients diagnosed with hepatic neuroendocrine neoplasms, excluding other sites of origin through general examination and postoperative follow-up. The CT and MR signs were analyzed according to the 2018 version of Liver Imaging Reporting and Data System (LI-RADS), along with causes of misdiagnosis. Results: Twelve patients, including 6 males and 6 females, were enrolled in this study. There was no significant increase in liver tumor markers among all cases. Most masses were multiple (9/12), exhibiting low attenuation on pre-contrast CT scans, T1-hypointense signal, T2-hyperintense signal, and restricted diffusion. The majority of these masses (7/10) demonstrated similar rim arterial phase hyper-enhancement as well as peripheral "washout" during venous portal phase and delayed phase imaging. Three cases had incomplete capsules while one case had a complete capsule. Cyst/necrosis was observed in 7 out of all cases following administration of contrast agent, with 5 mainly distributed in the periphery. All masses lacked fat, calcification, vascular or bile duct tumor thrombus formation. Conclusion: The imaging findings associated with PHNENs possess certain specificity, often presenting as multiple masses within the liver accompanied by peripheral cyst/necrosis, similar rim arterial phase hyper-enhancement during venous portal phase and delayed phase imaging.
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BACKGROUND: TG103, a glucagon-like peptide-1 analog, is being investigated as an option for weight management. We aimed to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of TG103 injection in participants who are overweight or obese without diabetes. METHODS: In this randomized, double-blind, placebo-controlled, multiple-dose phase 1b study, participants aged 18-75 years with a body-mass index (BMI) ≥ 26.0 kg/m2 and body weight ≥ 60 kg were enrolled from three centers in China. The study included three cohorts, and in each cohort, eligible participants were randomly assigned (3:1) to one of three once-weekly subcutaneous TG103 groups (15.0, 22.5 and 30.0 mg) or matched placebo, without lifestyle interventions. In each cohort, the doses of TG103 were escalated in 1-week intervals to the desired dose over 1 to 4 weeks. Then participants were treated at the target dose until week 12 and then followed up for 2 weeks. The primary endpoint was safety and tolerability assessed by the incidence and severity of adverse events (AEs) from baseline to the end of the follow-up period. Secondary endpoints included pharmacokinetic and pharmacodynamic profiles of TG103 and the occurrence of anti-drug antibodies to TG103. RESULTS: A total of 147 participants were screened, and 48 participants were randomly assigned to TG103 (15.0, 22.5 and 30.0 mg groups, n = 12 per group) or placebo (n = 12). The mean (standard deviation, SD) age of the participants was 33.9 (10.0) years; the mean bodyweight was 81.65 (10.50) kg, and the mean BMI was 29.8 (2.5) kg/m2. A total of 466 AEs occurred in 45 of the 48 participants, with 35 (97.2%) in the TG103 group and 10 (83.3%) in the pooled placebo group. Most AEs were grade 1 or 2 in severity, and there were no serious adverse events (SAEs), AEs leading to death, or AEs leading to discontinuation of treatment. The steady-state exposure of TG103 increased with increasing dose and was proportional to Cmax,ss, AUCss, AUC0-t and AUC0-inf. The mean values of Cmax,ss ranged from 951 to 1690 ng/mL, AUC0-t ranged from 150 to 321 µg*h/mL, and AUC0-inf ranged from 159 to 340 µg*h/mL. TG103 had a half-life of 110-116 h, with a median Tmax of 36-48 h. After treatment for 12 weeks, the mean (SD) values of weight loss from baseline in the TG103 15.0 mg, 22.5 mg and 30.0 mg groups were 5.65 (3.30) kg, 5.35 (3.39) kg and 5.13 (2.56) kg, respectively, and that in the placebo group was 1.37 (2.13) kg. The least square mean percent weight loss from baseline to D85 in all the TG103 groups was more than 5% with p < 0.05 for all comparisons with placebo. CONCLUSIONS: In this trial, all three doses of once-weekly TG103 were well tolerated with an acceptable safety profile. TG103 demonstrated preliminary 12-week body weight loss without lifestyle interventions, thus showing great potential for the treatment of overweight and obesity. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04855292. Registered on April 22, 2021.
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Obesidad , Sobrepeso , Humanos , Persona de Mediana Edad , Masculino , Adulto , Femenino , Método Doble Ciego , Obesidad/tratamiento farmacológico , Sobrepeso/tratamiento farmacológico , Anciano , Adulto Joven , Adolescente , China , Placebos/administración & dosificación , Inyecciones Subcutáneas , Péptido 1 Similar al GlucagónRESUMEN
BACKGROUND: Some patients with cancer-administered anti-cancer drugs may develop renal lesions with low-level enhancement on follow-up abdominal computed tomography (CT). OBJECTIVE: To explore the clinical significance of renal lesions with low-level enhancement on CT after exposure to anti-cancer drugs. METHODS: Medical records of patients with cancer who developed renal lesions on CT after exposure to anti-cancer drugs were retrospectively reviewed. Renal lesions were scored according to the extent of involvement, CT attenuation values of lesions and normal parenchyma were measured on precontrast CT and three phases of contrast-enhanced CT, and changes in serum creatinine (SCr) from one week before exposure to drugs to one week before and after the appearance of renal lesions were recorded. RESULTS: This study included 54 patients (86 lesions). Lesions were slightly lower density on pre-contrast CT, and less enhancing than normal renal parenchyma, especially in the delayed phase. Lesions were wedge-shaped, and involved the renal pyramid and associated renal cortex, as well as, were single or multiple, and occurred in the unilateral or bilateral kidneys. There were patchy and cord-like shadows of increased density in adjacent perirenal adipose tissue. During follow-up, lesions disappeared in 15 patients and persisted in 39 patients without significant progression. There were significant differences in renal lesions and normal renal parenchyma CT attenuation values in each phase of contrast-enhanced CT. Change in SCr level was significantly positively correlated with lesion score. CONCLUSION: Renal lesions with low-level enhancement on CT suggest early drug-induced kidney injury. These findings will inform clinical decision-making.
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The utilization of functional cling films presents a promising approach to alleviate post-harvest spoilage caused by microbial activity, oxidative metabolism, and moisture loss in agricultural products. To overcome the environmental problems of conventional packaging materials, in this study, we developed functional fruit and vegetable cling films based on glycidyltrimethylammonium chloride and rosemarinic acid cross-linked gelatin (RQ-GEL). The results indicate that the prepared RQ-GEL film possesses excellent UV light barrier properties and mechanical performance. RQ-GEL inhibited S. aureus and E. coli by 93.79% and 92.04%, respectively. DPPH and ABTS free radical scavenging activities were as high as 87.69% and 84.6%. In the cherry tomato preservation experiment, when compared to uncovered samples, the RQ-GEL group had a 29.77% reduction in weight loss and a significant 26.92% reduction in hardness. Meanwhile, the RQ-GEL group delays the decline of fruit total soluble solids and titratable acidity content, and prolongs the preservation period of cherry tomatoes. Hence, RQ-GEL cling film is poised to emerge as a promising packaging material for the post-harvest preservation of agricultural products.
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OBJECTIVES: Age and sex characteristics are evident in cephalometric radiographs (CRs), yet their accurate estimation remains challenging due to the complexity of these images. This study aimed to harness deep learning to automate age and sex estimation from CRs, potentially simplifying their interpretation. STUDY DESIGN: We compared the performance of 4 deep learning models (SVM, R-net, VGG16-SingleTask, and our proposed VGG16-MultiTask) in estimating age and sex from the testing dataset, utilizing a VGG16-based multitask deep learning model on 4,557 CRs. Gradient-weighted class activation mapping (Grad-CAM) was incorporated to identify sex. Performance was assessed using mean absolute error (MAE), specificity, sensitivity, F1 score, and the area under the curve (AUC) in receiver operating characteristic analysis. RESULTS: The VGG16-MultiTask model outperformed the others, with the lowest MAE (0.864±1.602) and highest sensitivity (0.85), specificity (0.88), F1 score (0.863), and AUC (0.93), demonstrating superior efficacy and robust performance. CONCLUSIONS: The VGG multitask model demonstrates significant potential in enhancing age and sex estimation from cephalometric analysis, underscoring the role of AI in improving biomedical interpretations.
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Cefalometría , Redes Neurales de la Computación , Determinación del Sexo por el Esqueleto , Humanos , Masculino , Femenino , Determinación del Sexo por el Esqueleto/métodos , Adolescente , Sensibilidad y Especificidad , Determinación de la Edad por el Esqueleto/métodos , Niño , Adulto , Aprendizaje ProfundoRESUMEN
Osteosclerosis in multiple myeloma (MM) is typically associated with rare POEMS syndrome, characterized by polyneuropathy (P), organomegaly (O), endocrinopathy (E), M-protein (M), and skin changes (S). However, osteosclerosis in multiple myeloma (MM) without POEMS syndrome, defined as non-POEMS Osteosclerotic MM, is exceedingly rare. We report a 70-year-old man with rib pain, remarkably high bone mineral density and diffuse osteosclerosis. The diagnosis of non-POEMS osteosclerotic MM was confirmed by biopsy and aspiration of bone marrow through surgery. A literature review spanning from 1990 identified 12 cases of similar non-POEMS osteosclerotic MM, including 5 males and 7 females with a mean age of 59.7 ± 10.6 years. The non-POEMS osteosclerotic MM can be divided into two subtypes, the osteosclerotic lesion subtype and the diffuse osteosclerosis subtype. Absence of polyneuropathy and organomegaly are the main factors that differentiate non-POEMS osteosclerotic MM from POEMS. A hyperactive osteoblastic process might be the etiology of diffuse osteosclerosis. Further research is needed to understand its etiology and pathophysiology.
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Plague, as an ancient zoonotic disease caused by Yersinia pestis, has brought great disasters. The natural plague focus of Marmota himalayana in the Qinghai-Tibet Plateau is the largest, which has been constantly active and the leading source of human plague in China for decades. Understanding the population genetics of M. himalayana and relating that information to the biogeographic distribution of Yersinia pestis and plague outbreaks are greatly beneficial for the knowledge of plague spillover and arecrucial for pandemic prevention. In the present research, we assessed the population genetics of M. himalayana. We carried out a comparative study of plague outbreaks and the population genetics of M. himalayana on the Qinghai-Tibet Plateau. We found that M. himalayana populations are divided into two main clusters located in the south and north of the Qinghai-Tibet Plateau. Fourteen DFR genomovars of Y. pestis were found and exhibited a significant region-specific distribution. Additionally, the increased genetic diversity of plague hosts is positively associated with human plague outbreaks. This insight gained can improve our understanding of biodiversity for pathogen spillover and provide municipally directed targets for One Health surveillance development, which will be an informative next step toward increased monitoring of M. himalayana dynamics.
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Marmota , Yersinia pestis , Animales , Humanos , Tibet/epidemiología , China/epidemiología , Brotes de Enfermedades , Yersinia pestis/genética , Variación GenéticaRESUMEN
PURPOSE: Although many studies have investigated the association between psoriasis and chronic obstructive pulmonary disease (COPD), the causal relationship between psoriasis and COPD is still unknown. METHODS: We employed bidirectional Mendelian randomization to investigate the causal relationship between psoriasis and COPD. Genetic instruments for exposure were selected from two distinct genome-wide association study databases. Single nucleotide polymorphisms associated with exposures at the genome-wide significance level (p < 5 × 10^-8 ) and exhibiting low linkage disequilibrium (r^2 < 0.001) were chosen as instrumental variables. Causality was assessed using multiple MR methods, including Inverse-Variance Weighted (IVW), MR-Egger, Weighted Median, Simple Mode, and Weighted Mode. A significance level of p < 0.05 was considered statistically significant. Heterogeneity was examined using Cochran's Q test, and MR-Egger regression was employed to detect pleiotropy. The robustness and reliability of the results were further evaluated through leave-one-out analysis. RESULTS: We found a positive causal association between psoriasis and COPD [IVW: odds ratio (OR): 1.0006; p = 0.0056]. Heterogeneity and pleiotropy have not been discovered, so the results of the study are reliable. In the reverse analysis, no causal association between CPOD and psoriasis was found. CONCLUSION: Our findings revealed that psoriasis was associated with an elevated risk of COPD. However, no causal association between COPD and psoriasis was identified in our study.
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Psoriasis , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Reproducibilidad de los Resultados , Psoriasis/epidemiología , Psoriasis/genética , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/genéticaRESUMEN
The rotes of attempted and completed suicide among adolescents are increasing globally. Social support can help decrease the risk of adolescent suicide, but this aspect has been rarely studied in China. The present study aimed to use the Delphi methodology to establish a set of guidelines for the development of social support resources, with the goal of collectively reducing suicide risks among adolescents in Shanghai. We commenced the study in April 2021, established a research team, searched the keywords using Web of Science from 2016 to 2021 and ultimately designed a pre-evaluation index. Next, following Donabedian's Structure-Process-Outcome model, the research developed a questionnaire comprising 3 level-1, 12 level-2, and 73 level-3 indicators. Ten experts were enlisted to conduct three rounds of e-mail inquiries in order to finalize the indicator system, resulting in 2 level-1, 11 level-2, and 52 level-3 indicators, as well as expert consensus. Our findings indicate that the social support systems should include parents, schools, psychiatric hospitals, social organizations, and government departments, with the government sector being the most important ((M = 9.4). Furthermore, our study revealed that school counselors and psychologists play similar roles to psychiatrists within the interdisciplinary team (M ± S = 9.2 ± 1.1). As per the expert consensus, social support systems should strengthen government-led and interdisciplinary collaboration, prioritize suicide prevention in schools and encourage greater involvement from social organizations.
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Aripiprazole modulates functional connectivity (FC) between several brain regions in first-episode schizophrenia patients, contributing to improvement in clinical symptoms. However, the effects of aripiprazole on abnormal connections among extensive brain networks in schizophrenia patients remain unclear. We aimed to investigate the effects of 12 weeks of aripiprazole treatment on the FC of large-scale brain networks. Forty-five first-episode drug-naïve schizophrenia patients and 45 healthy controls were recruited for this longitudinal study. Resting-state functional magnetic resonance imaging (fMRI) data were collected at baseline and after 12 weeks of aripiprazole treatment. The patients were classified into those in response (SCHr group) and non-response (SCHnr group) according to the improvement of clinical symptoms after 12-weeks treatment. The FC were evaluated for seven large-scale brain networks. In addition, correlation analysis was performed to investigate associations between changes FC of large-scale brain networks and clinical symptoms. Before aripiprazole treatment, schizophrenia patients showed decreased FC of extensive brain networks compared to healthy controls. The 12-week aripiprazole treatment significantly prevented the constantly decreased FC of subcortical network, default mode network and other brain networks in patients with SCHr, in association with the improvement of clinical symptoms. Taken together, these findings have revealed the effects of aripiprazole on FC in large-scale networks in schizophrenia patients, which could provide new insight on interpreting symptom improvement in SCH.
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Esquizofrenia , Humanos , Esquizofrenia/diagnóstico por imagen , Esquizofrenia/tratamiento farmacológico , Aripiprazol/farmacología , Estudios Longitudinales , Imagen por Resonancia Magnética , Encéfalo , Mapeo Encefálico , Vías Nerviosas/diagnóstico por imagenRESUMEN
The escalating accumulation of plastic waste in ecosystems poses a significant health concern to soil environment, yet the environmental effects of plastics remains largely unexplored. Biodegradable plastics could offer a viable alternative to conventional persistent plastics, but our understanding of their potential benefits or detrimental effects on the decomposition of plant debris by soil biomass is limited. In this study, we conducted a year-long field experiment to examine the environmental response and impact on plant debris decomposition in the presence of varying quantities of persistent versus biodegradable plastics. Our findings indicate that the decomposition rate decreased by 2.8-4.9% for persistent plastics, while it increased by 1.3-4.2% for biodegradable plastics. Persistent plastics primarily induced adverse effects, including a reduction in soil nutrients, microbial diversity, bioturbation, enzyme activity, easily decomposable carbon, and microbial biomass carbon in plant debris. In contrast, biodegradable plastics resulted in beneficial effects such as an increase in enzyme activity, microbial biomass carbon, and easily decomposable carbon. We also observed that the decomposition rate of plant residues and nutrient release are closely associated with changes in the organic carbon chemical structure induced by different plastic film fragments. A significant shift in alkoxy carbon content facilitated the release of nutrients and soluble carbon, while modifications in carboxyl and aromatic carbon content hindered their release. Overall, our study reveals over one year that biodegradable plastics primarily induce positive effects on the decomposition of soil organic matter.
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Plásticos Biodegradables , Suelo , Suelo/química , Ecosistema , Compuestos Orgánicos , Carbono , Plásticos/químicaRESUMEN
Helical-conical optical beams (HCOBs) have attracted considerable interest due to their peculiar optical features. Their characteristic helical light intensity distribution has exerted unprecedented advantages in many fields, but multiple combinations of HCOBs have not been reported due to the limitations of algorithms and light field modulation techniques. We propose and experimentally demonstrate arbitrary combinations of multiple HCOBs in free space to construct hybrid HCOB arrays. The similarity between the experimental results and the numerical simulation results is 94.22%. The initial orientation of the HCOBs is flexibly tuned by the rotation factor ß, and the optical pen is used to combine the HCOBs. This approach allows multiple parameters in the array to be precisely tuned, including the type, number, and position of HCOBs, adding more design flexibility. The constructed HCOB arrays have a higher degree of modulation freedom and may find applications in fields where dynamic control is in high demand, including optical tweezers, biological cell sorting, and multiparticle manipulation.
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CRISPR (clustered regularly interspaced short palindromic repeats) and CRISPR-associated protein (Cas) have gained extensive applications in bioassays. However, CRISPR-based detection platforms are often hampered by limited analytical sensitivity, while nucleic acid-based amplification strategies are usually indispensable for additional signal enhancement with potential risks of amplification leakages. To address these challenges, an amplification-free CRISPR-based bioassay of aflatoxin B1 (AFB1) was proposed by applying single nanoparticle counting. Single-particle mode inductively coupled plasma mass spectrometry (Sp-ICPMS) has been regarded as a sensitive tool for nanoparticle counting since one nanoparticle can generate considerable signals above backgrounds. With AFB1, activator strands were introduced to initiate the trans-cleavage of CRISPR/Cas12a for cutting the nanoparticles-tagged-magnetic beads, which were transduced to nanoparticle count signals after separation. Finally, a pico-mole level limit-of-detections (LODs) with moderate selectivity was achieved. Certified reference materials (CRMs) analysis and recovery tests were conducted with promising results. To our best knowledge, this is the first report of the single particle counting-based CRISPR/Cas12a biosensing study.
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Técnicas Biosensibles , Nanopartículas , Aflatoxina B1 , Sistemas CRISPR-Cas , Bioensayo , CertificaciónRESUMEN
BACKGROUND: Polycystic ovary syndrome (PCOS) is a common chronic condition in women of child-bearing age. There is currently no effective treatment, so early and long-term management is essential. However, there are many problems in the practice of disease management in women with PCOS that make it difficult to achieve good outcomes. OBJECTIVE: To explore women's experience of PCOS management and identify the relevant facilitators and barriers to management. SEARCH STRATEGY: A structured search was undertaken in five bibliographic databases (MEDLINE, Web of Science, CINAHL, Embase, PubMed, and Cochrane) from the date of establishment of the database up to December 2022. SELECTION CRITERIA: All qualitative and mixed-methods studies available in English describing the experience of PCOS management from the patients' perspective were included. DATA COLLECTION AND ANALYSIS: The Joanna Briggs Institute Qualitative Assessment and Review Instrument was used to appraise study quality. The evidence was synthesized using a pragmatic meta-aggregative approach guided by the capability, opportunity, and motivation model of behavior (COM-B). MAIN RESULTS: A total of 13 studies were included with 85 equivocal findings and 12 credible findings. The findings were meta-aggregated into three themes: (1) capability of women with PCOS, including patients' attitudes toward disease and management, knowledge, and skills of the disease; (2) opportunities in PCOS management, including information about PCOS, diagnostic delay, disease characteristics, disease management plan, and logistical and environmental problems; and (3) motivation in PCOS management, including impact of symptoms, perceived needs, support and feedback, and unpleasant medical experience. CONCLUSIONS: This study identifies facilitators and barriers to PCOS management from the patient perspective, which can guide the design and implementation of PCOS management programs for patients. This study also provides information for future research into how the COM-B theory can be incorporated into specific management plans to promote patient action.
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Síndrome del Ovario Poliquístico , Humanos , Femenino , Síndrome del Ovario Poliquístico/diagnóstico , Síndrome del Ovario Poliquístico/terapia , Diagnóstico Tardío , MotivaciónRESUMEN
An aggregation induced emission based compound ((E)-4-((2-hydroxy-5-methoxybenzylidene)amino)benzoic acid) was synthesized through facile Schiff base condensation and characterized by various spectral techniques. The as-prepared compound represented a typical aggregation induced emission behavior in aqueous solution and exploited as a turn-off fluorescent sensor for Fe3+ detection in THF-H2O system (3:7, v/v) with high sensitivity and selectivity. The mechanism of the fluorescence quenching was intensively studied, which was attributed to both dynamic quenching and inner filter effect. The fluorescence probe displayed a highly broad dynamic response range (0.5-500 µM) for selective detection of Fe3+ with a limit of detection of 0.079 µM. The proposed method was successfully employed for detection and quantification of Fe3+ in human urine samples and proved to have potential for practical applications in biological field.
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G protein-coupled receptors (GPCRs) are versatile and vital proteins involved in a wide array of physiological processes and responses, such as sensory perception (e.g., vision, taste, and smell), immune response, hormone regulation, and neurotransmission. Their diverse and essential roles in the body make them a significant focus for pharmaceutical research and drug development. Currently, approximately 35% of marketed drugs directly target GPCRs, underscoring their prominence as therapeutic targets. Recent advances in structural biology have substantially deepened our understanding of GPCR activation mechanisms and interactions with G-protein and arrestin signaling pathways. This review offers an in-depth exploration of both traditional and recent methods in GPCR structure analysis. It presents structure-based insights into ligand recognition and receptor activation mechanisms and delves deeper into the mechanisms of canonical and noncanonical signaling pathways downstream of GPCRs. Furthermore, it highlights recent advancements in GPCR-related drug discovery and development. Particular emphasis is placed on GPCR selective drugs, allosteric and biased signaling, polyphamarcology, and antibody drugs. Our goal is to provide researchers with a thorough and updated understanding of GPCR structure determination, signaling pathway investigation, and drug development. This foundation aims to propel forward-thinking therapeutic approaches that target GPCRs, drawing upon the latest insights into GPCR ligand selectivity, activation, and biased signaling mechanisms.
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As the third largest global food crop, potato plays an important role in ensuring food security. However, it is particularly sensitive to high temperatures, which seriously inhibits its growth and development, thereby reducing yield and quality and severely limiting its planting area. Therefore, rapid, and high-throughput screening for high-temperature response genes is highly significant for analyzing potato high-temperature tolerance molecular mechanisms and cultivating new high-temperature-tolerant potato varieties. We screened genes that respond to high temperature by constructing a potato cDNA yeast library. After high-temperature treatment at 39 °C, the yeast library was subjected to high-throughput sequencing, and a total of 1931 heat resistance candidate genes were screened. Through GO and KEGG analysis, we found they were mainly enriched in "photosynthesis" and "response to stimuli" pathways. Subsequently, 12 randomly selected genes were validated under high temperature, drought, and salt stress using qRT-PCR. All genes were responsive to high temperature, and most were also induced by drought and salt stress. Among them, five genes ectopically expressed in yeast enhance yeast's tolerance to high temperatures. We provide numerous candidate genes for potato response to high temperature stress, laying the foundation for subsequent analysis of the molecular mechanism of potato response to high temperature.