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1.
J Colloid Interface Sci ; 674: 745-752, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38955006

RESUMO

The exploration of novel electrochemiluminescence (ECL) luminophores with excellent ECL properties is a current research hotspot in the ECL field. Herein, a novel high-efficiency Ru-complex-free ECL emitter PyTS-Zr-BTB-MOL has been prepared by using porous ultrathin Zr-BTB metal-organic layer (MOL) as carrier to coordinatively graft the cheap and easily available polycyclic aromatic hydrocarbon (PAH) derivative luminophore PyTS whose ECL performance has never been investigated. Gratifyingly, the ECL intensity and efficiency of PyTS-Zr-BTB-MOL were markedly enhanced compared to both PyTS monomers and PyTS aggregates. The main reason was that the distance between pyrene rings was greatly expanded after the PyTS grafting on the Zr6 clusters of Zr-BTB-MOL, which overcame the aggregation-caused quenching (ACQ) effect of PyTS and thus enhanced the ECL emission. Meanwhile, the porous nanosheet structure of PyTS-Zr-BTB-MOL could distinctly increase the exposure of PyTS luminophores and shorten the diffusion paths of coreactants and electrons/ions, which effectively promoted the electrochemical excitation of more PyTS luminophores and thus achieved a further ECL enhancement. In light of the remarkable ECL property of PyTS-Zr-BTB-MOL, it was employed as an ECL indicator to build a novel high-sensitivity ECL biosensor for microRNA-21 determination, possessing a satisfactory response range (100 aM to 100 pM) and an ultralow detection limit (10.4 aM). Overall, this work demonstrated that using MOLs to coordinatively graft the PAH derivative luminophores to eliminate the ACQ effect and increase the utilization rate of the luminophores is a promising and efficient strategy to develop high-performance Ru-complex-free ECL materials for assembling ultrasensitive ECL biosensing platforms.

2.
Mol Cell ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38955180

RESUMO

During implantation, embryos undergo an unpolarized-to-polarized transition to initiate postimplantation morphogenesis. However, the underlying molecular mechanism is unknown. Here, we identify a transient transcriptional activation governing embryonic morphogenesis and pluripotency transition during implantation. In naive pluripotent embryonic stem cells (ESCs), which represent preimplantation embryos, we find that the microprocessor component DGCR8 can recognize stem-loop structures within nascent mRNAs to sequester transcriptional coactivator FLII to suppress transcription directly. When mESCs exit from naive pluripotency, the ERK/RSK/P70S6K pathway rapidly activates, leading to FLII phosphorylation and disruption of DGCR8/FLII interaction. Phosphorylated FLII can bind to transcription factor JUN, activating cell migration-related genes to establish poised pluripotency akin to implanting embryos. Resequestration of FLII by DGCR8 drives poised ESCs into formative pluripotency. In summary, we identify a DGCR8/FLII/JUN-mediated transient transcriptional activation mechanism. Disruption of this mechanism inhibits naive-poised-formative pluripotency transition and the corresponding unpolarized-to-polarized transition during embryo implantation, which are conserved in mice and humans.

4.
Blood Press Monit ; 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38958504

RESUMO

OBJECTIVES: To determine the independent effect of high-sensitivity C-reactive protein (hs-CRP) and the combined effects of hs-CRP and other traditional risk factors on microalbuminuria in hypertensive patients during the 3-year follow-up period. METHODS AND RESULTS: Baseline hs-CRP levels and other risk factors were measured in 280 adults in 2007. In the third year of examination, 199 patients (mean age 62.5 ±â€…9.5, men 59.3%) were approached for the measurement of microalbuminuria. The subjects were classified into two groups by the median of baseline hs-CRP. Compared to the patients with baseline hs-CRP below the median group (n = 99, 50%), the group with baseline hs-CRP above the median (n = 100, 50%) had higher urinary albumin-to-creatinine ratio (ACR) (P = 0.007) at the end of follow-up period. ACR at the end of follow-up period was significantly correlated with baseline diabetes (ß = 0.342; P < 0.001), baseline SBP (ß = 0.148; P = 0.02), and baseline log-transformed hs-CRP (ß = 0.169; P = 0.01), while adversely correlated with baseline estimated glomerular filtration rate (eGFR) (ß = -0.163; P = 0.02) in multivariate stepwise linear analysis. In addition, ACR change during follow-up period was significantly correlated with baseline diabetes (ß = 0.359; P < 0.001) and baseline log-transformed hs-CRP (ß = 0.190; P = 0.004) in multivariate stepwise linear analysis. The combined effects of baseline hs-CRP and conventional risk factors, such as male sex, diabetes, smoking status, hyperlipidemia, hyperuricemia, and mildly reduced eGFR had a greater risk for microalbuminuria progression. There was no difference in eGFR changes during the follow-up period between two groups. CONCLUSION: Our findings offer a new piece of evidence on the predictive value of baseline hs-CRP for microalbuminuria progression in essential hypertensive patients, and highlight those who combined with traditional cardiovascular risk factors had a greater risk for developing microalbuminuria.

5.
Mol Neurobiol ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958889

RESUMO

As a risk factor for Alzheimer's disease (AD), studies have demonstrated that long-term high-fat diet (HFD) could accelerate the deposition of amyloid beta (Aß) in the brain. The glymphatic system plays a critical role in Aß clearance from the brain. However, studies investigating the effects of long-term HFD on glymphatic function have reported paradoxical outcomes, and whether glymphatic dysfunction is involved in the disturbance of Aß clearance in long-term HFD-fed mice has not been determined. In the present study, we injected fluorescently labeled Aß into the hippocampus and found that Aß clearance was decreased in HFD-fed mice. We found that long-term HFD-fed mice had decreased glymphatic function by injecting fluorescent tracers into the cisterna magna and corpus striatum. In long-term HFD-fed mice, aquaporin-4 (AQP4) polarization in the cortex was disrupted, and glymphatic clearance activity was positively correlated with the AQP4 polarization index. In HFD-fed mice, the disturbance of Aß clearance from the hippocampus was exacerbated by TGN-020, a specific inhibitor of AQP4, whereas TGN-073, an enhancer of AQP4, ameliorated it. These findings suggest that long-term HFD disrupts Aß clearance by inhibiting AQP4-mediated glymphatic function. The underlying mechanism may involve the disruption of AQP4 polarization.

7.
J Hepatocell Carcinoma ; 11: 1207-1219, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38946843

RESUMO

Purpose: To observe and assess the efficacy and safety of donafenib combined with transarterial chemoembolization (TACE) to treat unresectable hepatocellular carcinoma (HCC). Patients and Methods: This prospective, single-arm, single-center, phase II clinical study enrolled 36 patients with initial unresectable HCC who had not undergone any systemic treatment. The patients received donafenib plus TACE (n = 26) or donafenib plus TACE plus programmed death receptor 1 inhibitors (n = 10). The primary endpoint was short-term efficacy, with secondary endpoints including progression-free survival (PFS), time to response (TTR), disease control rate (DCR), and adverse events. The tumor feeding artery diameter was also measured. Results: Efficacy evaluation of all 36 patients revealed 6 cases of complete response, 19 of partial response, 8 of stable disease, and 3 of progressive disease. Six (16.7%) patients successfully underwent conversion surgery, all achieving R0 resection, and 2 (5.6%) achieved a complete pathological response. The objective response rate (ORR) was 69.4% and the DCR was 91.7%. The median PFS was 10.7 months, the median overall survival was not reached, and the median TTR was 1.4 months. The median survival rates at 6, 12, and 18 months were 85.0%, 77.6%, and 71.3%, respectively. The median PFS rates at 6, 12, and 18 months were 65.3%, 45.6%, and 34.2%, respectively. Treatment-related adverse events (TRAEs) occurred in all 25 subjects, including 4 (11.3%) grade 3 TRAEs. No grade 4 or 5 TRAEs occurred. The tumor feeding artery diameter was significantly decreased following treatment (P = 0.036). Multivariable analysis revealed the sum of baseline target lesion diameters, best tumor response, and combined immunotherapy as independent predictors of PFS. Conclusion: TACE plus donafenib reduced the tumor feeding artery diameter in patients with unresectable HCC. The safety profile was good, and a high ORR was achieved.

8.
Front Microbiol ; 15: 1407760, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38946896

RESUMO

Introduction: Salinization damages soil system health and influences microbial communities structure and function. The response of microbial functions involved in the nutrient cycle to soil salinization is a valuable scientific question. However, our knowledge of the microbial metabolism functions in salinized soil and their response to salinity in arid desert environments is inadequate. Methods: Here, we applied metagenomics technology to investigate the response of microbial carbon (C), nitrogen (N), phosphorus (P), and sulfur (S) cycling and the key genes to salinity, and discuss the effects of edaphic variables on microbial functions. Results: We found that carbon fixation dominated the carbon cycle. Nitrogen fixation, denitrification, assimilatory nitrate reduction (ANRA), and nitrogen degradation were commonly identified as the most abundant processes in the nitrogen cycle. Organic phosphorus dissolution and phosphorus absorption/transport were the most enriched P metabolic functions, while sulfur metabolism was dominated by assimilatory sulfate reduction (ASR), organic sulfur transformation, and linkages between inorganic and organic sulfur transformation. Increasing salinity inhibited carbon degradation, nitrogen fixation, nitrogen degradation, anammox, ANRA, phosphorus absorption and transport, and the majority of processes in sulfur metabolism. However, some of the metabolic pathway and key genes showed a positive response to salinization, such as carbon fixation (facA, pccA, korAB), denitrification (narG, nirK, norBC, nosZ), ANRA (nasA, nirA), and organic phosphorus dissolution processes (pstABCS, phnCD, ugpAB). High salinity reduced the network complexity in the soil communities. Even so, the saline microbial community presented highly cooperative interactions. The soil water content had significantly correlations with C metabolic genes. The SOC, N, and P contents were significantly correlated with C, N, P, and S network complexity and functional genes. AP, NH4+, and NO3- directly promote carbon fixation, denitrification, nitrogen degradation, organic P solubilization and mineralization, P uptake and transport, ASR, and organic sulfur transformation processes. Conclusion: Soil salinity in arid region inhibited multiple metabolic functions, but prompted the function of carbon fixation, denitrification, ANRA, and organic phosphorus dissolution. Soil salinity was the most important factor driving microbial functions, and nutrient availability also played important roles in regulating nutrient cycling.

9.
ACS Omega ; 9(25): 27369-27396, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38947842

RESUMO

MCL-1, an antiapoptotic member of the BCL-2 family, is dysregulated and overexpressed in various tumors. In tumors with MCL-1 overexpression, selective inhibitors of MCL-1 are expected to overcome the drug resistance caused by BCL-2 inhibitors currently used in clinical treatment. Here, we employed docking-based virtual screening to identify an active hit, LC126, with binding affinity around 10 µM for MCL-1 and BCL-2. Under the guidance of structure-based design, we obtained a few selective inhibitors of MCL-1 after three rounds of structural optimization. The representative compound GQN-B37-E exhibited binding affinity for MCL-1 at the submicromolar range (K i = 0.6 µM) without apparent binding to BCL-2 or BCL-XL. 15N-heteronuclear single-quantum coherence NMR spectra suggested that this compound binds to the BH3-domain-binding pocket in the MCL-1 surface. Cellular assays revealed that GQN-B37-Me, the precursor of GQN-B37-E, is effective particularly on leukemia cells (such as H929 and MV-4-11) to induce caspase-dependent apoptosis. Its interaction with MCL-1 in cells was confirmed by coimmunoprecipitation. Administration of GQN-B37-Me to MV-4-11 xenograft mice at 50 mg/kg every 2 days for 20 days led to 43% tumor growth inhibition. GQN-B37-Me also exhibited reasonable in vitro stability in GSH and liver microsomes from several species. This new class of MCL-1 inhibitor may have potential to be further developed into a preclinical candidate for treating leukemia.

10.
Haematologica ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38961734

RESUMO

Generation of mammalian red blood cells requires the expulsion of polarized nuclei late in terminal erythroid differentiation. However, the mechanisms by which spherical erythroblasts determine the direction of nuclear polarization and maintain asymmetry during nuclear expulsion are poorly understood. Given the analogy of erythroblast enucleation to asymmetric cell division and the key role of Aurora kinases in mitosis, we sought to investigate the function of Aurora kinases in erythroblast enucleation. We found that AURKA (Aurora kinase A) is abundantly expressed in orthochromatic erythroblasts. Intriguingly, high-resolution confocal microscopy analyses revealed that AURKA co-localized with the centrosome on the side of the nucleus opposite its membrane contact point during polarization and subsequently translocated to the anterior end of the protrusive nucleus upon nuclear exit. Mechanistically, AURKA regulated centrosome maturation and localization via interaction with i-tubulin to provide polarization orientation for the nucleus. Furthermore, we identified ECT2 (epithelial cell transforming 2), a guanine nucleotide exchange factor, as a new interacting protein and ubiquitination substrate of AURKA. After forming the nuclear protrusion, AURKA translocated to the anterior end of the protrusive nucleus to directly degrade ECT2, which is partly dependent on kinase activity of AURKA. Moreover, knockdown of ECT2 rescued impaired enucleation caused by AURKA inhibition. Our findings have uncovered a previously unrecognized role of Aurora kinases in the establishment of nuclear polarization and eventual nuclear extrusion and provide new mechanistic insights into erythroblast enucleation.

11.
Elife ; 132024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38959062

RESUMO

Bacterial exonuclease III (ExoIII), widely acknowledged for specifically targeting double-stranded DNA (dsDNA), has been documented as a DNA repair-associated nuclease with apurinic/apyrimidinic (AP)-endonuclease and 3'→5' exonuclease activities. Due to these enzymatic properties, ExoIII has been broadly applied in molecular biosensors. Here, we demonstrate that ExoIII (Escherichia coli) possesses highly active enzymatic activities on ssDNA. By using a range of ssDNA fluorescence-quenching reporters and fluorophore-labeled probes coupled with mass spectrometry analysis, we found ExoIII cleaved the ssDNA at 5'-bond of phosphodiester from 3' to 5' end by both exonuclease and endonuclease activities. Additional point mutation analysis identified the critical residues for the ssDNase action of ExoIII and suggested the activity shared the same active center with the dsDNA-targeted activities of ExoIII. Notably, ExoIII could also digest the dsDNA structures containing 3'-end ssDNA. Considering most ExoIII-assisted molecular biosensors require the involvement of single-stranded DNA (ssDNA) or nucleic acid aptamer containing ssDNA, the activity will lead to low efficiency or false positive outcome. Our study revealed the multi-enzymatic activity and the underlying molecular mechanism of ExoIII on ssDNA, illuminating novel insights for understanding its biological roles in DNA repair and the rational design of ExoIII-ssDNA involved diagnostics.


Assuntos
DNA de Cadeia Simples , Escherichia coli , Exodesoxirribonucleases , Exodesoxirribonucleases/metabolismo , Exodesoxirribonucleases/genética , DNA de Cadeia Simples/metabolismo , DNA de Cadeia Simples/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Escherichia coli/enzimologia , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética
12.
Food Chem ; 458: 140233, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38964093

RESUMO

To analyze the effect of various drying treatments (microwave drying (MD), hot air drying (HAD), vacuum drying (VD), and vacuum freeze drying (VFD)) on taste compounds in Penaeus vannamei, relevant indicators such as free amino acids, 5'-nucleotides, and organic acids were performed. Multidimensional infrared spectroscopy (MM-IR) results found that there were notable variations in taste properties of P. vannamei. There were 18 autocorrelation peaks in 3400-900 cm-1 were screened using second-derivative infrared spectroscopy (SD-IR) and two-dimensional correlation infrared spectroscopy (2DCOS-IR). Variations in functional groups were the major contributors to taste profiles. The TAV of glutamic acid (Glu), guanine (GMP), and inosinemonphosphate (IMP) were greater than one and had notable impacts on taste profiles. VD had the highest equivalent umami value, followed by VFD, HAD, and MD. This study may provide a theoretical guide for the production of dried P. vannamei products on an industrial scale.

13.
J Colloid Interface Sci ; 675: 64-73, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38964125

RESUMO

Artificial colloidal motors capable of converting various external energy into mechanical motion, have emerged as attractive photosensitizer (PS) nanocarriers with good deliverability for photodynamic therapy. However, photoactivated 3O2-to-1O2 transformation as the most crucial energy transfer of the photodynamic process itself is still challenging to convert into autonomous transport. Herein, we report on PS-loaded thiophane-containing semiconducting conjugated polymer (SCP)-based polymer colloidal motors with asymmetric geometry for photodynamic-regulated propulsion in the liquid. The asymmetrical presence of the SCP phases within the colloidal motors would lead to significant differences in the 3O2-to-1O2 transformation and 1O2 release manners between asymmetrical polymer phases, spontaneously creating asymmetrical osmotic pressure gradients across the nanoparticles for powering the self-propelled motion under photodynamic regulation. This photoactivated energy-converting behavior can be also combined with the photothermal conversion of the SCP phases to create two energy gradients exerting diffusiophoretic/thermophoretic force on the colloidal motors for achieving multimode synergistic propulsion. This unique motile feature endows the light-driven PS nanocarriers with good permeability against various physiological barriers in the tumor microenvironment for enhancing antitumor efficacy, showing great potential in phototherapy.

14.
Artif Intell Med ; 154: 102926, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38964193

RESUMO

Pathological myopia (PM) is the leading ocular disease for impaired vision worldwide. Clinically, the characteristics of pathology distribution in PM are global-local on the fundus image, which plays a significant role in assisting clinicians in diagnosing PM. However, most existing deep neural networks focused on designing complex architectures but rarely explored the pathology distribution prior of PM. To tackle this issue, we propose an efficient pyramid channel attention (EPCA) module, which fully leverages the potential of the clinical pathology prior of PM with pyramid pooling and multi-scale context fusion. Then, we construct EPCA-Net for automatic PM recognition based on fundus images by stacking a sequence of EPCA modules. Moreover, motivated by the recent pretraining-and-finetuning paradigm, we attempt to adapt pre-trained natural image models for PM recognition by freezing them and treating the EPCA and other attention modules as adapters. In addition, we construct a PM recognition benchmark termed PM-fundus by collecting fundus images of PM from publicly available datasets. The comprehensive experiments demonstrate the superiority of EPCA-Net over state-of-the-art methods in the PM recognition task. For example, EPCA-Net achieves 97.56% accuracy and outperforms ViT by 2.85% accuracy on the PM-fundus dataset. The results also show that our method based on the pretraining-and-finetuning paradigm achieves competitive performance through comparisons to part of previous methods based on traditional fine-tuning paradigm with fewer tunable parameters, which has the potential to leverage more natural image foundation models to address the PM recognition task in limited medical data regime.

15.
China CDC Wkly ; 6(26): 619-623, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38966310

RESUMO

What is already known about this topic?: Since May 2022, a global outbreak of mpox has emerged in more than 100 non-endemic countries. As of December 2023, over 90,000 cases had been reported. The outbreak has predominantly affected men who have sex with men (MSM), with sexual contact identified as the principal mode of transmission. What is added by this report?: Since June 2023, China has faced an occurrence of mpox, predominantly affecting the MSM population. Approximately 90% of those affected reported engaging in homosexual behavior within 21 days prior to symptom onset, a trend that aligns with the global outbreak pattern. The prompt identification of cases, diligent tracing of close contacts, and the implementation of appropriate management strategies have successfully mitigated the spread of mpox virus in China. What are the implications for public health practice?: We propose that mpox is transmitted locally within China. Drawing from our experiences in controlling the virus spread, it is crucial to investigate and formulate effective surveillance and educational strategies. Importantly, we must encourage high-risk populations to promptly seek medical care upon the onset of symptoms.

16.
Front Nutr ; 11: 1403497, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38966420

RESUMO

Introduction: Resistant starch (RS) has garnered attention for its health benefits, including modulating the gut microbiota and promoting the production of short-chain fatty acids (SCFAs). Methods: This study investigates structural changes of type 3 resistant starch from Canna edulis (CE) during in vitro simulated digestion and explores its health-relevant properties using healthy individuals' fecal microbiota. Results: CE, prepared with a RS content of 59.38%, underwent a comprehensive analysis employing X-ray diffraction (XRD), fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). During simulated digestion, XRD analysis demonstrated a significant rise in CE's relative crystallinity from 38.92 to 49.34%. SEM illustrated the transition of CE from a smooth to a rough surface, a notable morphological shift. Post-digestion, CE was introduced into microbial fermentation. Notably, propionic acid and valeric acid levels significantly increased compared to the control group. Furthere more, beneficial Bifidobacterium proliferated while pathogenic Escherichia-Shigella was suppressed. When comparing CE to the well-known functional food fructo-oligosaccharide (FOS), CE showed a specific ability to support the growth of Bifidobacterium and stimulate the production of short-chain fatty acids (SCFAs) without causing lactic acid accumulation. Discussion: CE demonstrates potential as a functional health food, with implications for gut health enhancement and SCFAs production.

17.
Drug Alcohol Depend Rep ; 11: 100246, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38966567

RESUMO

Background: Few studies have investigated changes in brain structure and function associated with recovery from cocaine use disorder (CUD), and fewer still have identified brain changes associated with specific CUD treatments, which could inform treatment development and optimization. Methods: In this longitudinal study, T1-weighted magnetic resonance imaging scans were acquired from 41 methadone-maintained individuals with CUD (15 women) at the beginning of and after 12 weeks of outpatient treatment. As part of a larger randomized controlled trial, these participants were randomly assigned to receive (or not) computer-based training for cognitive behavioral therapy (CBT4CBT), and galantamine (or placebo). Results: Irrespective of treatment condition, whole-brain voxel-based morphometry analyses revealed a significant decrease in right caudate body, bilateral cerebellum, and right middle temporal gyrus gray matter volume (GMV) at post-treatment relative to the start of treatment. Subsequent region of interest analyses found that greater reductions in right caudate and bilateral cerebellar GMV were associated with higher relative and absolute levels of cocaine use during treatment, respectively. Participants who completed more CBT4CBT modules had a greater reduction in right middle temporal gyrus GMV. Conclusions: These results extend previous findings regarding changes in caudate and cerebellar GMV as a function of cocaine use and provide the first evidence of a change in brain structure as a function of engagement in digital CBT for addiction. These data suggest a novel potential mechanism underlying how CBT4CBT and CBT more broadly may exert therapeutic effects on substance-use-related behaviors through brain regions implicated in semantic knowledge.

18.
Front Public Health ; 12: 1386500, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38966703

RESUMO

Background: The aim of this study was to classify distinct subgroups of adolescents based on the severity levels of their mobile phone addiction and to investigate how these groups differed in terms of their psychosocial characteristics. We surveyed a total of 2,230 adolescents using three different questionnaires to assess the severity of their mobile phone addiction, stress, anxiety, depression, psychological resilience, and personality. Latent class analysis was employed to identify the subgroups, and we utilized Receiver Operating Characteristic (ROC) curves and multinomial logistic regression for statistical analysis. All data analyses were conducted using SPSS 26.0 and Mplus 8.5. Methods: We classified the subjects into subgroups based on their mobile phone addiction severity, and the results revealed a clear pattern with a three-class model based on the likelihood level of mobile phone addiction (p < 0.05). We examined common trends in psychosocial traits such as age, grade at school, parental education level, anxiety levels, and resilience. ROC analysis of sensitivity versus 1-specificity for various mobile phone addiction index (MPAI) scores yielded an area under the curve (AUC) of 0.893 (95% CI, 0.879 to 0.905, p < 0.001). We also determined diagnostic value indices for potential cutoff points ranging from 8 to 40. The optimal cutoff value for MPAI was found to be >14, which corresponded to the maximum Youden index (Youden index = 0.751). Results: The latent classification process in this research confirmed the existence of three distinct mobile phone user groups. We also examined the psychosocial characteristics that varied in relation to the severity levels of addiction. Conclusion: This study provides valuable insights into the categorization of adolescents based on the severity of mobile phone addiction and sheds light on the psychosocial characteristics associated with different addiction levels. These findings are expected to enhance our understanding of mobile phone addiction traits and stimulate further research in this area.


Assuntos
Comportamento Aditivo , Telefone Celular , Análise de Classes Latentes , Resiliência Psicológica , Humanos , Adolescente , Masculino , Feminino , China , Comportamento Aditivo/psicologia , Telefone Celular/estatística & dados numéricos , Inquéritos e Questionários , Ansiedade/psicologia , Depressão/psicologia , Depressão/epidemiologia , Estresse Psicológico/psicologia , Comportamento do Adolescente/psicologia , Curva ROC
19.
Cancer Lett ; : 217101, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38969156

RESUMO

The tumor microenvironment (TME) consists of tumor cells, non-tumor cells, extracellular matrix, and signaling molecules, which can contribute to tumor initiation, progression, and therapy resistance. In response to starvation, hypoxia, and drug treatments, tumor cells undergo a variety of deleterious endogenous stresses, such as hypoxia, DNA damage, and oxidative stress. In this context, to survive the difficult situation, tumor cells evolve multiple conserved adaptive responses, including metabolic reprogramming, DNA damage checkpoints, homologous recombination, up-regulated antioxidant pathways, and activated unfolded protein responses. In the last decades, the protein O-GlcNAcylation has emerged as a crucial causative link between glucose metabolism and tumor progression. Here, we discuss the relevant pathways that regulate the above responses. These pathways are adaptive adjustments induced by endogenous stresses in cells. In addition, we systematically discuss the role of O-GlcNAcylation-regulated stress-induced adaptive response pathways (SARPs) in TME remodeling, tumor progression, and treatment resistance. We also emphasize targeting O-GlcNAcylation through compounds that modulate OGT or OGA activity to inhibit tumor progression. It seems that targeting O-GlcNAcylated proteins to intervene in TME may be a novel approach to improve tumor prognosis.

20.
Br J Cancer ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38969866

RESUMO

BACKGROUND: Invadopodia facilitate cancer cell extravasation, but the molecular mechanism whereby invadopodia-specific proteases such as MT1-MMP are called to invadopodia is unclear. METHODS: Mass spectrometry and immunoprecipitation were used to identify interactors of MT1-MMP in metastatic breast cancer cells. After identification, siRNA and small molecule inhibitors were used to assess the effect these interactors had on cellular invasiveness. The chicken embryo chorioallantoic membrane (CAM) model was used to assess extravasation and invadopodia formation in vivo. RESULTS: In metastatic breast cancer cells, MT1-MMP was found to associate with plectin, a cytolinker and scaffolding protein. Complex formation between plectin and MT1-MMP launches invadopodia formation, a subtype we termed iplectin (i = invadopodial). iPlectin delivers MT1-MMP to invadopodia and is indispensable for regulating cell surface levels of the enzyme. Genetic depletion of plectin with siRNA reduced invadopodia formation and cell invasion in vitro. In vivo extravasation efficiency assays and intravital imaging revealed iplectin to be a key contributor to invadopodia ultrastructure and essential for extravasation. Pharmacologic inhibition of plectin using the small molecule Plecstatin-1 (PST-1) abrogated MT1-MMP delivery to invadopodia and extravasation efficiency. CONCLUSIONS: Anti-metastasis therapeutic approaches that target invadopodia are possible by disrupting interactions between MT1-MMP and iplectin. CLINICAL TRIAL REGISTRATION NUMBER: NCT04608357.

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