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1.
Methods Mol Biol ; 2852: 47-64, 2025.
Artículo en Inglés | MEDLINE | ID: mdl-39235736

RESUMEN

Electrochemical approaches, along with miniaturization of electrodes, are increasingly being employed to detect and quantify nucleic acid biomarkers. Miniaturization of the electrodes is achieved through the use of screen-printed electrodes (SPEs), which consist of one to a few dozen sets of electrodes, or by utilizing printed circuit boards. Electrode materials used in SPEs include glassy carbon (Chiang H-C, Wang Y, Zhang Q, Levon K, Biosensors (Basel) 9:2-11, 2019), platinum, carbon, and graphene (Cheng FF, He TT, Miao HT, Shi JJ, Jiang LP, Zhu JJ, ACS Appl Mater Interfaces 7:2979-2985, 2015). There are numerous modifications to the electrode surfaces as well (Cheng FF, He TT, Miao HT, Shi JJ, Jiang LP, Zhu JJ, ACS Appl Mater Interfaces 7:2979-2985, 2015). These approaches offer distinct advantages, primarily due to their demonstrated superior limit of detection without amplification. Using the SPEs and potentiostats, we can detect cells, proteins, DNA, and RNA concentrations in the nanomolar (nM) to attomolar (aM) range. The focus of this chapter is to describe the basic approach adopted for the use of SPEs for nucleic acid measurement.


Asunto(s)
Técnicas Biosensibles , Técnicas Electroquímicas , Electrodos , Grafito , Grafito/química , Técnicas Electroquímicas/métodos , Técnicas Electroquímicas/instrumentación , Técnicas Biosensibles/métodos , Técnicas Biosensibles/instrumentación , Ácidos Nucleicos/análisis , Humanos , ADN/análisis
2.
Eat Weight Disord ; 29(1): 57, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39231917

RESUMEN

PURPOSE: Emerging research evidence suggests positive relationships between higher screen time and eating disorders. However, few studies have examined the prospective associations between screen use and eating disorder symptoms in early adolescents and how problematic screen use may contribute to symptom development. METHODS: We analyzed prospective cohort data from the Adolescent Brain Cognitive Development (ABCD) Study (N = 10,246, 2016-2020, ages 9-14). Logistic regression analyses were used to estimate the longitudinal associations between baseline self-reported screen time and eating disorder symptoms in year two. Logistic regression analyses were also used to estimate cross-sectional associations between problematic screen use in year two (either problematic social media or mobile phone use) and eating disorder symptoms in year two. Eating disorder symptoms based on the Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS-5) included fear of weight gain, self-worth tied to weight, engaging in compensatory behaviors, binge eating, and distress with binge eating. RESULTS: Each additional hour of total screen time and social media use was associated with higher odds of fear of weight gain, self-worth tied to weight, compensatory behaviors to prevent weight gain, binge eating, and distress with binge eating two years later (odds ratio [OR] 1.05-1.55). Both problematic social media and mobile phone use were associated with higher odds of all eating disorder symptoms (OR 1.26-1.82). CONCLUSIONS: Findings suggest greater total screen time, social media use, and problematic screen use are associated with more eating disorder symptoms in early adolescence. Clinicians should consider assessing for problem screen use and, when high, screen for disordered eating. LEVEL OF EVIDENCE: Level III: Evidence obtained from well-designed cohort or case-control analytic studies.


Asunto(s)
Trastornos de Alimentación y de la Ingestión de Alimentos , Tiempo de Pantalla , Medios de Comunicación Sociales , Humanos , Adolescente , Trastornos de Alimentación y de la Ingestión de Alimentos/diagnóstico , Trastornos de Alimentación y de la Ingestión de Alimentos/psicología , Masculino , Femenino , Niño , Estudios Prospectivos , Estudios Transversales , Conducta del Adolescente/psicología
3.
Front Hum Neurosci ; 18: 1337851, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39253069

RESUMEN

Introduction: Alzheimer's disease and related dementias (ADRD) represent a substantial global public health challenge with multifaceted impacts on individuals, families, and healthcare systems. Brief cognitive screening tools such as the Mini-Cog© can help improve recognition of ADRD in clinical practice, but widespread adoption continues to lag. We compared the Digital Clock and Recall (DCR), a next-generation process-driven adaptation of the Mini-Cog, with the original paper-and-pencil version in a well-characterized clinical trial sample. Methods: DCR was administered to 828 participants in the Bio-Hermes-001 clinical trial (age median ± SD = 72 ± 6.7, IQR = 11; 58% female) independently classified as cognitively unimpaired (n = 364) or as having mild cognitive impairment (MCI, n = 274) or dementia likely due to AD (DLAD, n = 190). MCI and DLAD cohorts were combined into a single impaired group for analysis. Two experienced neuropsychologists rated verbal recall accuracy and digitally drawn clocks using the original Mini-Cog scoring rules. Inter-rater reliability of Mini-Cog scores was computed for a subset of the data (n = 508) and concordance between Mini-Cog rule-based and DCR scoring was calculated. Results: Inter-rater reliability of Mini-Cog scoring was good to excellent, but Rater 2's scores were significantly higher than Rater 1's due to variation in clock scores (p < 0.0001). Mini-Cog and DCR scores were significantly correlated (τ B = 0.71, p < 0.0001). However, using a Mini-Cog cut score of 4, the DCR identified more cases of cognitive impairment (n = 47; χ 2 = 13.26, p < 0.0005) and Mini-Cog missed significantly more cases of cognitive impairment (n = 87). In addition, the DCR correctly classified significantly more cognitively impaired cases missed by the Mini-Cog (n = 44) than vice versa (n = 4; χ 2 = 21.69, p < 0.0001). Discussion: Our findings demonstrate higher sensitivity of the DCR, an automated, process-driven, and process-based digital adaptation of the Mini-Cog. Digital metrics capture clock drawing dynamics and increase detection of diagnosed cognitive impairment in a clinical trial cohort of older individuals.

4.
Laryngoscope ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39263883

RESUMEN

This article, accompanied by technical notes and video, presents a case of an 85-year-old patient with a cT2N0 laryngeal squamous cell carcinoma treated using CO2 transoral laser exoscopic surgery (TOLES). The procedure achieved en bloc tumor removal with negative margins, preserving laryngeal and swallowing functions, demonstrating TOLES as a viable alternative to traditional microsurgery with enhanced visualization and ergonomics. Laryngoscope, 2024.

5.
Artículo en Inglés | MEDLINE | ID: mdl-39263935

RESUMEN

BACKGROUND: We aim to discover which, if any, of the subscales of internalizing and externalizing behavioral problems at age 3 are still associated with screen time (ST) at age 2 after adjusting for behavioral problems scores at age 2. METHODS: This study was conducted under the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Information was gathered prospectively, with 7207 mother-child pairs included in the analysis. Children's ST was categorized in hours a day at age 2 (<1, 1-<2, 2-<4, ≥4). We assessed children's behavioral problems using the Child Behavior Checklist for Ages 1½-5 (CBCL) at ages 2 and 3. 'Having behavioral problems' was defined by them being within a clinical range for internalizing behaviors (withdrawn, somatic complaints, anxious/depressed and emotionally reactive) and externalizing behaviors (attention problems and aggressive behaviors) at age 3. Continuous scores on each of the behavioral problem scales at age 2 were used as covariates. RESULTS: Greater ST for children at age 2 was associated with specific subscales for emotionally reactive and aggressive behaviors at age 3. CONCLUSIONS: This study found that ST is prospectively associated with some behavioral scales but not others.

6.
Clin Exp Pediatr ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39265626

RESUMEN

Background: Screen-based activity refers to the use of screened devices, which are changing from stationary devices such as televisions and desktop computers to newer portable devices such as smartphones and electronic tablets. The exposure of younger children to all types of screened devices has increased. Purpose: This review aimed to provide an overview of previous studies and identify the correlations associated with screen-based activities in preschoolers. Methods: We conducted a systematic literature review of databases including PubMed, Embase, and PsycInfo targeting quantitative studies published between 2010 and 2019. We then analyzed the associations between screen time and various individual, familial, and environmental factors in healthy children aged 0-6 years. We specifically included studies that provided a subgroup analysis for this age category to systematically identify the factors influencing screen time patterns among preschoolers. Results: The search yielded 36 articles that met the inclusion criteria. We investigated age, sex, and social, family, and personal factors as well as media parenting. The results suggested that media parenting for screen-based activities was an important protective factor. Conclusion: Limited research has been conducted on preschoolers' screen-based activities with both stationary and portable screened devices. Most factors have been studied using stationary devices and are too infrequent for solid conclusions to be reached. Parental screen time and the setting of appropriate media limits were crucial protective factors against excessive media exposure. However, information about family and personal factors remain scarce, and further research is needed.

7.
Clin Toxicol (Phila) ; : 1-7, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39230064

RESUMEN

BACKGROUND: Co-use of stimulants and opioids is often deliberate. However, the possibility remains that some people are unintentionally consuming fentanyl. To advance understanding of overdose risk, we examined the rate of concordance between self-reported fentanyl use and corresponding urine toxicology screen results. METHODS: Between August 2022-August 2023, 411 participants (adults who reported any non-medical drug use in the past three months) in Nevada and New Mexico completed a cross-sectional survey, of whom 64% (n = 270; the analytical sample) also completed a urine toxicology screen, which detects fentanyl use in the past three days. Positive predictive value, negative predictive value, sensitivity, and specificity were calculated using self-reported past three-day fentanyl use (yes/no) and urine toxicology screen results for the presence of fentanyl (positive/negative). RESULTS: Of the 270 participants who provided a urine sample, 268 are included in the descriptive statistics (two with inconclusive urine toxicology screen results were excluded). Of the 268 participants, 146 (54.5%) had a fentanyl-positive urine toxicology screen result, 122 (45.5%) had a fentanyl-negative urine toxicology screen result, 137 (51.1%) reported past three-day fentanyl use, and 130 (48.5%) reported no past three-day fentanyl use. Only 6.9% of those with a fentanyl-positive urine toxicology screen did not report recent fentanyl use. The sensitivity of self-reported fentanyl use was 93%, specificity was 97%, positive predictive value was 97%, and negative predictive value was 92%. DISCUSSION: The rate of unanticipated exposure to fentanyl (that is, positive urine screen and negative self-report) in this sample was low, at 6.9%. This runs counter to the national narrative that there is widespread unknown contamination of fentanyl in the drug supply. CONCLUSION: Future research is needed to further explore how people who use multiple substances interpret their overdose risk and what harm reduction methods they employ.

8.
Laryngoscope ; 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39230195

RESUMEN

OBJECTIVE: Given the prevalence of neonatal hearing loss (HL) associated with intrauterine viral exposures, the goal of this study is to provide information on neonatal HL in the context of the COVID-19 pandemic. METHODS: Data were drawn from the COVID-19 Mother Baby Outcomes (COMBO) Initiative. 1007 participants completed the newborn hearing screen as part of routine clinical care (COMBO-EHR cohort) and 555 completed the National Survey of Children's Health (NSCH) at 2 and/or 3 years of age for research purposes (COMBO-RSCH cohort). Maternal SARS-CoV-2 infection status during pregnancy was determined through electronic health records and maternal-reported questionnaires. RESULTS: In adjusted multivariate logistic regression models covarying for newborn age at assessment, mode of delivery, and gestational age at delivery, there was no significant association between intrauterine SARS-CoV-2 exposure and newborn hearing screening failure (OR = 1.05, 95% CI = 0.39-2.42, p = 0.91) in the COMBO-EHR cohort. In the COMBO-RSCH cohort, there were similar non-significant associations between intrauterine exposure to SARS-CoV-2 and maternal-reported concern for HL on the NSCH (OR = 1.19 [95% CI = 0.30-4.24], p = 0.79). CONCLUSION: There is no association between intrauterine exposure to SARS-CoV-2 and failed hearing screen in neonates. Similarly, based on the NSCH, there is no association between intrauterine exposure to SARS-CoV-2 and maternal-reported concern for hearing in toddlers. These results offer reassurance given the widespread nature of this pandemic with tens of millions of fetuses having a history of intrauterine exposure. LEVEL OF EVIDENCE: Level 4 Laryngoscope, 2024.

9.
Drug Alcohol Depend Rep ; 12: 100269, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39219738

RESUMEN

Background: An increase in opioid-related overdoses, notably from potent synthetic opioids like fentanyl, prompted this consideration of characteristics of emergency department (ED) patients with evidence for illicit fentanyl use or exposure, the correlation with intentional opioid misuse, and subsequent ED management. Methods: A retrospective review was performed of patients presenting to an urban academic medical center ED with evidence for illicit fentanyl use, determined by positive urine drug screens (UDS), from 6/2021 through 11/2021. Participant demographics, comorbidities, ED chief complaint and disposition, and evidence of intentional opioid misuse were considered. Secondary outcomes included provision of buprenorphine/naloxone and/or naloxone kits at discharge, ED recidivism, and six-month mortality. Bivariate comparisons and logistic regression models were performed. Results: Among 409 unique patients, most were white and male with a mean age of 39.4. Approximately half presented with opioid-related complaints. Evidence of intentional opioid misuse was identified in 72.6 % of patients. Black patients had 79 % lower odds of intentional opioid misuse compared to white patients. Regarding ED management, 28.8 % were discharged with buprenorphine/naloxone and 14.0 % with a naloxone kit. Black patients had 63 % lower odds of receiving buprenorphine/naloxone compared to white patients after controlling for covariates. Nearly 6 % of the study population died within six months of the initial ED visit. Conclusion: This fentanyl-focused review describes patient characteristics which largely mirror the epidemiology of the current opioid epidemic; however, despite evidence of objective exposure, it also suggests that Black patients may be less likely to use fentanyl intentionally. It also highlights potential disparities related to ED-based opioid misuse patient management.

10.
Reprod Health ; 21(1): 127, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39223548

RESUMEN

BACKGROUND: Previous studies indicated that excessive engagement in digital devices could lead to negative psychological impacts in general population. We aimed to determine the association of electronic screen exposure with depression among women in early pregnancy. METHODS: A cross-sectional study was conducted from June 2021 to June 2022. A total of 665 women in early pregnancy were recruited and the information included socio-demographic characteristics, screen exposure and Patient Health Questionnaire - 9 depression scale. RESULTS: Among the women in early pregnancy, the total daily smartphone viewing time was the longest (median [P25-P75], 5 [3-6] hours/day) in the three types of electronic screen exposure. The total daily smartphone viewing time (P = 0.015, OR[95%CI] = 1.09[1.11-1.18]), smartphone (P = 0.016, OR[95%CI] = 1.24[1.04-1.47]) and television viewing time (P = 0.006, OR[95%CI] = 1.35[1.09-1.67]) before nocturnal sleep were significantly associated with depression among women in early pregnancy. The thresholds calculated by receiver operator characteristic curves were 7.5 h/day, 1.5 h/day and 1.5 h/day, respectively. In addition, women with higher scores of smartphone addiction were more susceptible to depression (P<0.001, OR[95%CI] = 1.11[1.07-1.16]). The top three smartphone usages in women with depression were watching videos (22.0%), listening to music (20.9%) and playing games (16.7%). CONCLUSIONS: In conclusion, electronic screen exposure, including screen viewing time, smartphone addiction and problematic smartphone use was associated with depression among women in early pregnancy. Further studies are warranted to verify the conclusions.


Asunto(s)
Depresión , Tiempo de Pantalla , Teléfono Inteligente , Humanos , Femenino , Embarazo , Estudios Transversales , Adulto , Depresión/etiología , Adulto Joven , Complicaciones del Embarazo/psicología , Televisión
11.
J Child Lang ; : 1-13, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39301829

RESUMEN

In the current pre-registered study, we examined the associations between shared book reading, daily screen time, and vocabulary size in 1,442 12- and 24-month-old Norwegian infants. Our results demonstrate a positive association between shared reading and vocabulary in both age groups, and a negative association between screen time and vocabulary in 24-month-olds. Exploratory analyses revealed that the positive relationship between shared reading and expressive vocabulary in 12-month-olds was stronger in lower SES groups, suggesting that shared reading may act as a compensatory mechanism attenuating potentially impoverished learning environment and parent-infant interactions in low-SES families.

12.
J Colloid Interface Sci ; 678(Pt C): 430-440, 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39303561

RESUMEN

While spatial and time-resolved anti-counterfeiting technologies have gained increasing attention owing to their excellent tunable photoluminescence, achieving high-security-level anti-counterfeiting remains a challenge. Herein, we developed a spatial-time-dual-resolved anti-counterfeiting system using zero-dimensional (0D) organic-inorganic Mn(II) metal halides: (EMMZ)2MnBr4 (named M-1, EMMZ=1-Ethyl-3-Methylimidazolium Bromide) and (EDMMZ)2MnBr4 (named M-2, EDMMZ=1-Ethyl-2,3-Dimethylimidazolium Bromide). M-1 shows a bright green emission with a quantum yield of 78 %. It undergoes a phase transformation from the crystalline to molten state with phosphorescence quenching at 350 K. Reversible phase and luminescent conversion was observed after cooling down for 15 s. Notably, M-2 exhibits green light emission similar to M-1 but undergoes phase conversion and phosphorescence quenching at 390 K, with reversible conversion observed after cooling down for 5 s. The photoluminescence switching mode of on(green)-off-on(green) can be achieved by temperature control, demonstrating excellent performance with short response times and ultra-high cyclic reversibility. By leveraging the different quenching temperatures and reversible PL conversion times of M-1 and M-2, we propose a spatial-time-dual-resolved photoluminescence (PL) switching system that combines M-1 and M-2. This system enables multi-fold tuning of the PL switch for encryption and decryption through cationic engineering strategies by modulating temperature and cooling time. This work presents a novel and feasible design strategy for advanced-level anti-counterfeiting technology based on a spatial-time-dual-resolved system.

13.
Artículo en Inglés | MEDLINE | ID: mdl-39306782

RESUMEN

INTRODUCTION: Our study examined the longitudinal relationship between parenting stress and screen time, outdoor play, and sleep routines in toddler to preschool-aged children. METHOD: We conducted a descriptive quantitative analysis of a prospective observational cohort study of 300 families with an 18-month-old toddler who were followed for 2 years. Parenting stress was measured using a subscale of the Parenting Stress Index-4 Short Form at child age 18 months. Screen time, outdoor play, and sleep routines were parent-reported at child age 36 months. Multivariable regression estimated associations between parenting stress and screen time behaviors, outdoor play, and sleep routines. RESULTS: Data from 280 children (42.1% female) showed that 39.6% did not have rules around screen time and 82% of families reported frequently having the television on without anyone watching. In adjusted models, a 1-standard deviation increase in parenting stress at 18 months was associated with increased odds of having a television on without anyone watching (OR 1.26, 95% CI: 1.01, 1.57) and decreased odds of not having rules about the amount of screen time at 36 months (OR 0.75, 95% CI: 0.58, 0.96). DISCUSSION: Increased parenting stress in early childhood was associated with some suboptimal screen time behaviors and sleep routines when children were preschool-aged.

14.
Heliyon ; 10(17): e36889, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39296038

RESUMEN

Objective: To examine children's screen time use and sleep patterns over 2 years of the pandemic and the downstream associations with children's executive functions and behavioural problems, as well as the moderating effects of parental factors. Method: This longitudinal cohort study examined school-aged children's lifestyle and behavioural changes over 2 years of the pandemic across 6 timepoints (November 2020 to August 2022). Latent growth modeling (LGM) was used to identify changes in screen time and sleep duration and multivariate LGM was used to determine how parental stress, positive parenting, changes in children's screen time and sleep over time were associated with children's executive functions and mental health outcomes at the final time point. Results: A total of 198 parents (children's mean age = 9.14 years) were recruited and followed up. Non-school screen time was elevated at the initial timepoint (3.6 ± 2.3 h). Positive parenting at the initial timepoint was associated with lower screen time use in children (ß = -.19, p < .001; ß = -.19, p < .001, in internalizing and externalizing models). Children whose screen time use was constant during the pandemic had shorter sleep durations (ß = -.45, p < .05 in internalizing model). Executive function was predicted by sleep duration at the first timepoint (ß = -.55, p < .001; ß = .73, p < .001, in internalizing and externalizing models) and changes in screen time during the pandemic was associated with both internalizing and externalizing symptoms (ß = .58, p < .05; ß = .54, p < .05, in internalizing and externalizing models). Conclusion: Children's screen time decreased slightly but remained significantly higher than Canadian and International guidelines during 2 years of the pandemic. Positive parenting styles can have a significant impact on children's screen time use. Reducing excessive screen time can help improve sleep patterns and, consequently, cognitive, and emotional well-being in children.

15.
Proc Natl Acad Sci U S A ; 121(39): e2406325121, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39298484

RESUMEN

Immune evasion is not only critical for tumor initiation and progression, but also determines the efficacy of immunotherapies. Through iterative in vivo CRISPR screens with seven syngeneic tumor models, we identified core and context-dependent immune evasion pathways across cancer types. This valuable high-confidence dataset is available for the further understanding of tumor intrinsic immunomodulators, which may lead to the discovery of effective anticancer therapeutic targets. With a focus on triple-negative breast cancer (TNBC), we found that Mga knock-out significantly enhances antitumor immunity and inhibits tumor growth. Transcriptomics and single-cell RNA sequencing analyses revealed that Mga influences various immune-related pathways in the tumor microenvironment. Our findings suggest that Mga may play a role in modulating the tumor immune landscape, though the precise mechanisms require further investigation. Interestingly, we observed that low MGA expression in breast cancer patients correlates with a favorable prognosis, particularly in those with active interferon-γ signaling. These observations provide insights into tumor immune escape mechanisms and suggest that further exploration of MGA's function could potentially lead to effective therapeutic strategies in TNBC.


Asunto(s)
Inmunoterapia , Neoplasias de la Mama Triple Negativas , Microambiente Tumoral , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/inmunología , Neoplasias de la Mama Triple Negativas/terapia , Femenino , Animales , Humanos , Ratones , Inmunoterapia/métodos , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Línea Celular Tumoral , Sistemas CRISPR-Cas , Escape del Tumor/genética , Interferón gamma/metabolismo , Interferón gamma/inmunología , Interferón gamma/genética , Regulación Neoplásica de la Expresión Génica , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas/genética
16.
J Bone Miner Res ; 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39298571

RESUMEN

Dysregulated chondrocyte metabolism is an essential risk factor for osteoarthritis (OA) progression. Maintaining cartilage homeostasis represents a promising therapeutic strategy for the treatment of OA. However, no effective disease-modifying therapy is currently available to OA patients. To discover potential novel drugs for OA, we screened a small-molecule natural product drug library and identified deapi-platycodin D3 (D-PDD3), which was subsequently tested for its effect on extracellular matrix (ECM) properties and on OA progression. We found that D-PDD3 promoted the generation of ECM components in cultured chondrocytes and cartilage explants and that intra-articular injection of D-PDD3 delayed disease progression in a trauma-induced mouse model of OA. To uncover the underlying molecular mechanisms supporting these observed functions of D-PDD3, we explored the targets of D-PDD3 via a screening approach integrating surface plasmon resonance (SPR) with liquid chromatography -tandem mass spectrometry (LC-MS/MS). The screening results suggested that D-PDD3 targeted tyrosine-protein phosphatase non-receptor type 1 (PTP1B), deletion of which restored chondrocyte homeostasis and markedly attenuated destabilization of the medial meniscus (DMM)-induced OA. Further cellular and molecular analyses showed that D-PDD3 maintained cartilage homeostasis by directly binding to PTP1B and consequently suppressing the PKM2/AMPK pathway. These findings demonstrated that D-PDD3 was a potential therapeutic drug for the treatment of OA and that PTP1B served as a protein target for the development of drugs to treat OA. This study provided significant insights into the development of therapeutics for OA treatment, which in turn helpd to improve the quality of life of OA patients and to reduce the health and economic burden.


OA is a degenerative disease with a high prevalence and consequently causes a burden to society. However, there is no convincing DMOAD exhibiting effective therapeutic effects on OA. In this study, we screened a small-molecule natural product drug library and identified deapi-platycodin D3, which was subsequently tested for its effect on extracellular matrix properties and on OA progression. Further cellular and in vivo experiments showed that D-PDD3 maintains cartilage homeostasis by directly binding to PTP1B and consequently suppressing the PKM2/AMPK pathway. Our results provided fundamental evidence for applying D-PDD3-based therapies against OA, which in turn helps to improve the quality of life in OA patients and to reduce the health and economic burdern.

17.
bioRxiv ; 2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-39229156

RESUMEN

Over a hundred risk genes underlie risk for autism spectrum disorder (ASD) but the extent to which they converge on shared downstream targets to increase ASD risk is unknown. To test the hypothesis that cellular context impacts the nature of convergence, here we apply a pooled CRISPR approach to target 29 ASD loss-of-function genes in human induced pluripotent stem cell (hiPSC)-derived neural progenitor cells, glutamatergic neurons, and GABAergic neurons. Two distinct approaches (gene-level and network-level analyses) demonstrate that convergence is greatest in mature glutamatergic neurons. Convergent effects are dynamic, varying in strength, composition, and biological role between cell types, increasing with functional similarity of the ASD genes examined, and driven by cell-type-specific gene co-expression patterns. Stratification of ASD genes yield targeted drug predictions capable of reversing gene-specific convergent signatures in human cells and ASD-related behaviors in zebrafish. Altogether, convergent networks downstream of ASD risk genes represent novel points of individualized therapeutic intervention.

18.
Bioorg Chem ; 153: 107802, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39244972

RESUMEN

The treatment of bladder cancer is limited by low drug efficacy and drug resistance. Hence, this study aimed to screen and identify potential drug precursors and investigate their mechanism of action. A set of camptothecin derivatives showing high anti-tumor potential was selected from early-stage research or literature and synthesized to construct a compound library. A total of 135 compounds were screened in T24 and J82 cells, revealing that FL118 significantly inhibited the proliferation of GC (gemcitabine + cisplatin)-sensitive/insensitive cells. FL118 exhibited excellent penetration and killing ability in organoids and three GC-insensitive patient-derived xenografts. Chemical proteomic and docking calculations were employed to identify binding proteins, indicating that FL118 can bind into H2A.X and its entwined DNA. The results of Cellular thermal shift assay and surface plasmon resonance (Kd = 3.77E-6) support the above findings. Fluorescence localization revealed widespread binding of FL118 within the cell nucleus. Furthermore, WB showed that FL118 increased cellular DNA damage, resulting in significant cell cycle inhibition. The binding of FL118 to H2A.X hindered the damage repair process, leading to apoptosis. Controllable adverse reactions were observed in mice treated with FL118. In conclusion, FL118 may be a superior anti-bladder cancer compound that acts as a molecular glue binding to both H2A.X and DNA. The resistance mediated by the DNA damage repair to DNA damage caused by GC regimen can be reversed by FL118. This distinct mechanism of FL118 has the potential to complement existing mainstream treatment approaches for bladder cancer.

19.
Child Care Health Dev ; 50(5): e13329, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39245883

RESUMEN

BACKGROUND: The increased trends in psychological distress and mental illness have been of great significance in public health concerns. The study aimed to investigate the proportion and correlates of meeting 24-h movement guidelines (including moderate to vigorous physical activity, screen time and sleep duration) and the associations between 24-h movement guidelines met and mental well-being and psychological distress in a large sample of Chinese students. METHODS: All participants received a physical examination and filled out questionnaires in this study. Chi-square tests were used to analyse the proportion of reaching 24-h guidelines by gender and logistic regression was used to analyse correlates of meeting 24-h guidelines. Two binary logistic regression models were used to analyse the association between meeting 24-h guidelines and mental well-being and psychological distress. The back-propagation artificial neural network was used to describe the importance of the independent variables. RESULTS: The findings revealed a generally low rate of meeting the 24-h movement guidelines, particularly concerning moderate to vigorous physical activity (16.5%). Meeting all three guidelines was related to better mental health in both boys and girls. Particularly, meeting screen time guideline and meeting sleep duration guideline appeared to be more important on mental outcomes, compared to meeting moderate to vigorous physical activity guideline. Compared with boys, girls were more susceptible to the influences of 24-h movement guidelines on mental health. CONCLUSIONS: Meeting all three components of the 24-h movement guidelines was associated with the most favourable mental health outcomes for both boys and girls. Thus, maintaining a daily balance of sufficient physical activity, limited screen time, and adequate sleep is crucial for enhancing the mental health status of students.


Asunto(s)
Ejercicio Físico , Salud Mental , Tiempo de Pantalla , Estudiantes , Humanos , Masculino , Femenino , Estudios Transversales , China , Estudiantes/psicología , Ejercicio Físico/psicología , Adolescente , Distrés Psicológico , Sueño , Encuestas y Cuestionarios , Niño , Factores Sexuales , Estrés Psicológico , Guías como Asunto , Pueblos del Este de Asia
20.
BMC Sports Sci Med Rehabil ; 16(1): 187, 2024 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-39243095

RESUMEN

BACKGROUND: The quest for a reliable and effective method to identify athletes at risk of injury holds the promise of significantly reducing injury rates and improving overall athletic performance. This research delved into the relationship between the Functional Movement Screen (FMS), Y-Balance Test (YBT), and Hop tests (Side hop, Medial triple hop, and Lateral step-down hop), aiming to determine the potential in predicting injuries of hop tests among division 1 volleyball and basketball players. METHODS: This research was conducted with fifty-two participants from the Division 1 league, encompassing both volleyball and basketball players. The study rigorously employed the Functional Movement Screen (FMS), the Y-Balance Test (YBT), and various hop tests (side hop test, medial triple hop test, lateral step-down hop) to measure relevant variables. The data analysis used logistic regression, ensuring a comprehensive approach to the study. RESULTS: Results showed no significant relationship between FMS and Hop test for predicting injuries, but there was a relationship between ΔY and side hop that shows side hop test can predict injury, but there was no relationship between Lateral step down, Medial triple hop, and ΔY. CONCLUSIONS: Based on our findings, side hop, despite the medial triple hop and lateral step-down test, can be used as a sports injury predictor.

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