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1.
Forensic Toxicol ; 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39122972

RESUMEN

PURPOSE: The abusive consumption of illegal E-cigarettes containing etomidate (ET) can have a significant impact on public mental and physical well-being. The purpose of this study is to establish a rapid quantitative method using ultra-high-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) for the targeted screening of etomidate (ET) and its metabolite etomidate acid (ETA) in hair samples. METHODS: A 1 mL methanol solution containing the internal standard ET-d5 at a concentration of 50 pg/mg was added to 20 mg of hair and milled below 4 °C. After centrifugation, 5 µL of the supernatant was injected into a UHPLC-MS/MS system. RESULTS: The limit of detection (LOD) and limit of quantification (LOQ) were determined to be 1 pg/mg and 10 pg/mg, respectively, for ET, and 10 pg/mg and 25 pg/mg, respectively, for ETA. Calibration curves for all analytes showed good linearity (r > 0.997), indicating a reliable method. Accuracies were between 92.12% and 110.72%. Intra-day and inter-day precision for all analytes at all concentration levels were below 10.13%. Analyte recoveries ranged from 86.90% to 101.43%, with a matrix effect ranging from -18.55% to -14.93%. CONCLUSIONS: The validated method was successfully used to analyze 105 hair samples from suspected ET users. Of these, 50 tested positive for ET and 43 tested positive for ETA above the LOQ. This demonstrates the effectiveness of the developed UHPLC-MS/MS method in detecting ET and ETA in hair samples, which could be instrumental in addressing the issue of illegal E-cigarette abuse and its impact on public health.

2.
Fa Yi Xue Za Zhi ; 40(3): 276-283, 2024 Jun 25.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-39166309

RESUMEN

Piperazines are a class of new psychoactive substances with hallucinogenic effects that affect the central nervous system by affecting the level of monoamine neurotransmitters. Abuse of piperazines will produce stimulating and hallucinogenic effects, accompanied by headache, dizziness, anxiety, insomnia, vomiting, chest pain, tachycardia, hypertension and other adverse reactions, and may even cause cardiovascular diseases and multiple organ failure and lead to death, seriously affecting human physical and mental health and public safety. The abuse of new psychoactive substance piperazines has attracted extensive attention from the international community. The study of its pharmacological toxicology and analytical methods has become a research hotspot in the field of forensic medicine. This paper reviews the in vivo processes, sample treatment and analytical methods of existing piperazines, in order to provide reference for forensic identification.


Asunto(s)
Piperazinas , Psicotrópicos , Detección de Abuso de Sustancias , Humanos , Piperazinas/análisis , Psicotrópicos/análisis , Detección de Abuso de Sustancias/métodos , Medicina Legal/métodos , Toxicología Forense/métodos , Alucinógenos/análisis , Trastornos Relacionados con Sustancias/diagnóstico
3.
bioRxiv ; 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39149252

RESUMEN

Digital pathology is a rapidly advancing field where deep learning methods can be employed to extract meaningful imaging features. However, the efficacy of training deep learning models is often hindered by the scarcity of annotated pathology images, particularly images with detailed annotations for small image patches or tiles. To overcome this challenge, we propose an innovative approach that leverages paired spatially resolved transcriptomic data to annotate pathology images. We demonstrate the feasibility of this approach and introduce a novel transfer-learning neural network model, STpath (Spatial Transcriptomics and pathology images), designed to predict cell type proportions or classify tumor microenvironments. Our findings reveal that the features from pre-trained deep learning models are associated with cell type identities in pathology image patches. Evaluating STpath using three distinct breast cancer datasets, we observe its promising performance despite the limited training data. STpath excels in samples with variable cell type proportions and high-resolution pathology images. As the influx of spatially resolved transcriptomic data continues, we anticipate ongoing updates to STpath, evolving it into an invaluable AI tool for assisting pathologists in various diagnostic tasks.

4.
Adv Mater ; : e2404797, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39030758

RESUMEN

2D perovskite passivation strategies effectively reduce defect-assisted carrier nonradiative recombination losses on the perovskite surface. Nonetheless, severe energy losses are causing by carrier thermalization, interfacial nonradiative recombination, and conduction band offset still persist at heterojunction perovskite/PCBM interfaces, which limits further performance enhancement of inverted heterojunction PSCs. Here, 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin (5FTPP) is introduced between 3D/2D perovskite heterojunction and PCBM. Compared to tetraphenylporphyrin without electron-withdrawing fluoro-substituents, 5FTPP can self-assemble with PCBM at interface into donor-acceptor (D-A) complex with stronger supramolecular interaction and lower energy transfer losses. This rapid energy transfer from donor (5FTPP) to acceptor (PCBM) within femtosecond scale is demonstrated to enlarge hot carrier extraction rates and ranges, reducing thermalization losses. Furthermore, the incorporation of polystyrene derivative (PD) reinforces D-A interaction by inhibiting self-π-π stacking of 5FTPP, while fine-tuning conduction band offset and suppressing interfacial nonradiative recombination via Schottky barrier, dipole, and n-doping. Notably, the multidentate anchoring of PD-5FTPP with FA+, Pb2+, and I- mitigates the adverse effects of FA+ volatilization during thermal stress. Ultimately, devices with PD-5FTPP achieve a power conversion efficiency of 25.78% (certified: 25.36%), maintaining over 90% of initial efficiency after 1000 h of continuous illumination at the maximum power point (65 °C) under ISOS-L-2 protocol.

5.
BMC Med ; 22(1): 303, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39026251

RESUMEN

BACKGROUND: To systematically analyze differences in atherosclerotic cardiovascular disease (ASCVD) burden between young and older adults. METHODS: We estimated the prevalence, mortality, and disability-adjusted life years (DALYs) of ASCVD, including ischemic heart disease (IHD), ischemic stroke (IS), and peripheral artery disease (PAD), in individuals aged 20-54 and > 55 years from 1990-2019, utilizing data from the 2019 Global Burden of Disease Study. The annual percentage changes (EAPCs) for age-specific prevalence, mortality, or DALY rates were calculated to quantify the temporal trends of ASCVD burden. We also analyzed population attribution fractions (PAF) of premature ASCVD mortality and DALYs for different risk factors and compared the burden of extremely premature, premature, and non-premature ASCVD cases based on clinical classifications. RESULTS: From 1990-2019, the global prevalence rates of IHD, IS, and PAD in the 20-54 years age group increased by 20.55% (from 694.74 to 837.49 per 100,000 population), 11.50% (from 439.48 to 490.03 per 100,000 population), and 7.38% (from 384.24 to 412.59 per 100,000 population), respectively. Conversely, the ASCVD prevalence in > 55years age group decreased. Adverse outcome burdens, including mortality and DALYs, varied among ASCVD subtypes. The decrease in the mortality/DALY burden of IHD and IS was lower in the 20-54 years group than in the > 55 years group. For PAD, DALYs among those aged 20-54 increased but decreased among those aged > 55 years. When grouped according to socio-demographic index (SDI) values, lower SDI regions exhibited a higher proportion of young ASCVD burden. The prevalence of young IHD, IS, and PAD in low SDI regions reached 20.70%, 40.05%, and 19.31% in 2019, respectively, compared with 12.14%, 16.32%, and 9.54%, respectively, in high SDI regions. Metabolic risks were the primary contributors to the ASCVD burden in both age groups. Increased susceptibility to ambient particulate matter pollution and inadequate control of high body-mass index and high fasting plasma glucose in young individuals may partially explain the differing temporal trends between young and older individuals. CONCLUSIONS: The ASCVD burden in young individuals may become a growing global health concern, especially in areas with lower socioeconomic development levels that require more effective primary prevention strategies.


Asunto(s)
Aterosclerosis , Carga Global de Enfermedades , Humanos , Persona de Mediana Edad , Adulto , Femenino , Masculino , Adulto Joven , Prevalencia , Carga Global de Enfermedades/tendencias , Aterosclerosis/epidemiología , Anciano , Factores de Riesgo , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/mortalidad , Factores de Edad , Años de Vida Ajustados por Discapacidad/tendencias , Enfermedad Arterial Periférica/epidemiología
6.
Methods Mol Biol ; 2812: 143-154, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39068360

RESUMEN

Single-cell RNA-sequencing (scRNA-seq) is a powerful technology that allows researchers to study gene expression heterogeneity within a tissue or cell population. One of the major advantages of scRNA-seq is that it allows researchers to identify and characterize novel cell types or subpopulations within a tissue that may be missed by traditional bulk RNA-sequencing methods. Although many existing methods have been developed to recognize known cell types, inferring novel cells may still be challenging in routine scRNA-seq analysis. Here we describe three lines of methods for inferring novel cells: unsupervised and outlier-detection-based methods, supervised and semi-supervised methods, and copy number variation (CNV)-based methods, as well as the corresponding situations that each method applies. We also provide implementation code and example usages to illustrate the available methods.


Asunto(s)
Variaciones en el Número de Copia de ADN , Análisis de Secuencia de ARN , Análisis de la Célula Individual , Análisis de la Célula Individual/métodos , Humanos , Análisis de Secuencia de ARN/métodos , Programas Informáticos , Biología Computacional/métodos , Perfilación de la Expresión Génica/métodos , RNA-Seq/métodos , Algoritmos , Animales
7.
World J Diabetes ; 15(6): 1263-1271, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38983812

RESUMEN

BACKGROUND: Cognitive dysfunction is the main manifestation of central neuropathy. Although cognitive impairments tend to be overlooked in patients with diabetes mellitus (DM), there is a growing body of evidence linking DM to cognitive dysfunction. Hyperglycemia is closely related to neurological abnormalities, while often disregarded in clinical practice. Changes in cerebral neurotransmitter levels are associated with a variety of neurological abnormalities and may be closely related to blood glucose control in patients with type 2 DM (T2DM). AIM: To evaluate the concentrations of cerebral neurotransmitters in T2DM patients exhibiting different hemoglobin A1c (HbA1c) levels. METHODS: A total of 130 T2DM patients were enrolled at the Department of Endocrinology of Shanghai East Hospital. The participants were divided into four groups according to their HbA1c levels using the interquartile method, namely Q1 (< 7.875%), Q2 (7.875%-9.050%), Q3 (9.050%-11.200%) and Q4 (≥ 11.200%). Clinical data were collected and measured, including age, height, weight, neck/waist/hip circumferences, blood pressure, comorbidities, duration of DM, and biochemical indicators. Meanwhile, neurotransmitters in the left hippocampus and left brainstem area were detected by proton magnetic resonance spectroscopy. RESULTS: The HbA1c level was significantly associated with urinary microalbumin (mALB), triglyceride, low-density lipoprotein cholesterol (LDL-C), homeostasis model assessment of insulin resistance (HOMA-IR), and beta cell function (HOMA-ß), N-acetylaspartate/creatine (NAA/Cr), and NAA/choline (NAA/Cho). Spearman correlation analysis showed that mALB, LDL-C, HOMA-IR and NAA/Cr in the left brainstem area were positively correlated with the level of HbA1c (P < 0.05), whereas HOMA-ß was negatively correlated with the HbA1c level (P < 0.05). Ordered multiple logistic regression analysis showed that NAA/Cho [Odds ratio (OR): 1.608, 95% confidence interval (95%CI): 1.004-2.578, P < 0.05], LDL-C (OR: 1.627, 95%CI: 1.119-2.370, P < 0.05), and HOMA-IR (OR: 1.107, 95%CI: 1.031-1.188, P < 0.01) were independent predictors of poor glycemic control. CONCLUSION: The cerebral neurotransmitter concentrations in the left brainstem area in patients with T2DM are closely related to glycemic control, which may be the basis for the changes in cognitive function in diabetic patients.

8.
Environ Sci Pollut Res Int ; 31(35): 48062-48072, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39017865

RESUMEN

Microalgae can promote antibiotic removal, which has attracted growing attention. However, its synergistic removal performance with bacteria in antibiotic pollutants is still poorly understood. In this study, firstly, we selected two green algae (Dictyosphaerium sp. and Chlorella sp.) and exposed them to Enrofloxacin (ENR) to observe their extracellular polysaccharides (EPS) concentration dynamic and the removal of antibiotics. Secondly, EPS was extracted and added to in situ lake water (no algae) to investigate its combined effect with bacteria. The results indicate that both Dictyosphaerium sp. and Chlorella sp. exhibited high tolerance to ENR stress. When the biomass of microalgae was low, ENR could significantly stimulate algae to produce EPS. The removal rates of Dictyosphaerium sp. and Chlorella sp. were 15.8% and 10.5%, respectively. The addition of EPS can both alter the microbial community structure in the lake water and promote the removal of ENR. The LEfSe analysis showed that there were significant differences in the microbial marker taxa, which promoted the increase of special functional bacteria for decomposing ENR, between the EPS-added group and the control group. The EPS of Dictyosphaerium sp. increased the abundance of Moraxellaceae and Spirosomaceae, while the EPS of Chlorella sp. increased the abundance of Sphingomonadaceae and Microbacteriaceae. Under the synergistic effect, Chlorella sp. achieved a maximum removal rate of 24.2%, while Dictyosphaerium sp. achieved a maximum removal rate of 28.9%. Our study provides new insights into the removal performance and mechanism of antibiotics by freshwater microalgae in water bodies and contribute to the development of more effective water treatment strategies.


Asunto(s)
Enrofloxacina , Microalgas , Contaminantes Químicos del Agua , Contaminantes Químicos del Agua/metabolismo , Antibacterianos , Chlorella/metabolismo , Lagos/microbiología , Microbiota
9.
Sci Immunol ; 9(97): eadk3981, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39058763

RESUMEN

Tumor-associated macrophages (TAMs) are a heterogeneous population of cells whose phenotypes and functions are shaped by factors that are incompletely understood. Herein, we asked when and where TAMs arise from blood monocytes and how they evolve during tumor development. We initiated pancreatic ductal adenocarcinoma (PDAC) in inducible monocyte fate-mapping mice and combined single-cell transcriptomics and high-dimensional flow cytometry to profile the monocyte-to-TAM transition. We revealed that monocytes differentiate first into a transient intermediate population of TAMs that generates two longer-lived lineages of terminally differentiated TAMs with distinct gene expression profiles, phenotypes, and intratumoral localization. Transcriptome datasets and tumor samples from patients with PDAC evidenced parallel TAM populations in humans and their prognostic associations. These insights will support the design of new therapeutic strategies targeting TAMs in PDAC.


Asunto(s)
Carcinoma Ductal Pancreático , Monocitos , Neoplasias Pancreáticas , Macrófagos Asociados a Tumores , Animales , Monocitos/inmunología , Humanos , Ratones , Macrófagos Asociados a Tumores/inmunología , Carcinoma Ductal Pancreático/inmunología , Carcinoma Ductal Pancreático/patología , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/patología , Diferenciación Celular/inmunología , Ratones Endogámicos C57BL , Ratones Transgénicos
10.
Mech Ageing Dev ; 220: 111955, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38852746

RESUMEN

While high-fat diet (HFD)-induced obesity is a major threat to global public health, the effect of HFD on cognition and insulin signaling during ageing remains controversial. The aim of this study was to characterize the dynamic alterations in cognition and cerebral insulin signaling during 6-month HFD consumption, and to investigate the potential therapeutic target and optimal timing to rescue obesity-related cognitive deficits. In the present study, impaired memory retention induced by 2-month HFD was recovered after 4 months on HFD. Prolonged (6-month) HFD did not further enhance tau hyperphosphorylation and ß-amyloid deposition, which was consistent with the alleviation of memory retention. In brain insulin signaling, 2-month HFD increased IRS-1 and p-IRS-1(Ser307)/IRS-1, while decreasing pAKT(Ser473)/AKT, PI3K and mTOR; 4-month HFD decreased IRS-1 and pAKT(Ser473)/AKT, while increasing AKT; 6-month HFD increased IRS-1, pAKT(Ser473)/AKT, and mTOR, while decreasing p-IRS-1(Ser307)/IRS-1, PI3K and AKT. Notably, bioinformatic analysis revealed a rhythmic process presented only in 4-month HFD group, with Srebf1 emerging as a link between circadian rhythms and insulin signaling pathway. These results suggest that prolonged HFD prevents further cognitive decline and the progression of Alzheimer's disease (AD)-related pathologies during ageing. Moreover, there may be a window for recovery, in which Srebf1 acts as a self-recovery switch to address obesity-related cognitive disorders in elders.


Asunto(s)
Cognición , Dieta Alta en Grasa , Proteínas Sustrato del Receptor de Insulina , Insulina , Transducción de Señal , Dieta Alta en Grasa/efectos adversos , Animales , Insulina/metabolismo , Masculino , Cognición/fisiología , Proteínas Sustrato del Receptor de Insulina/metabolismo , Ratones , Obesidad/metabolismo , Proteínas tau/metabolismo , Encéfalo/metabolismo , Péptidos beta-Amiloides/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Factores de Tiempo , Ratones Endogámicos C57BL
11.
J Cancer Res Clin Oncol ; 150(6): 317, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38914670

RESUMEN

INTRODUCTION: CD24 is a highly glycosylated glycosylphosphatidylinositol anchored membrane protein that plays an important role in tumor progression. The aim of this study was to investigate the effect of abnormal expression of CD24 on the proliferation, migration and invasion of breast cancer (BC) cells, and the molecular mechanism of regulating CD24 expression in breast cancer. METHODOLOGY: The bioinformatics method was used to predict the expression level of CD24 in BC and its relationship with the occurrence and development of BC. IHC, RT-qPCR and WB were used to detect the expression of CD24 in BC tissues and cells. The proliferation of CD24 was evaluated by CCK-8 and colony formation assay, and the migration and invasion of CD24 were evaluated by wound healing and transwell. In addition, the effect of CD24 on the malignancy of BC in vivo was further evaluated by subcutaneous tumorigenesis assay. Molecular mechanisms were measured by luciferase reporter assays, biotin-labeled miRNA pull-down assay, RIP, and western blotting. RESULTS: The results show that CD24 is highly expressed in breast cancer tissues and cell lines, and knockdown of CD24 in vivo and in vitro can inhibit the proliferation, migration and invasion of BC cells. Mechanistically, the transcription factor ZNF460 promotes its expression by binding to the CD24 promoter, and the expression of ZNF460 is regulated by miR-125a-5p, which inhibits its expression by targeting the 3'UTR of ZNF460. In addition, LINC00525 acts as a ceRNA sponge to adsorb miR-125a-5p and regulate its expression. CONCLUSIONS: Overexpression of CD24 is involved in the development and poor prognosis of BC, which can be used as a potential target for the treatment of BC and provide a theoretical basis for the treatment of BC.


Asunto(s)
Neoplasias de la Mama , Antígeno CD24 , Proliferación Celular , Progresión de la Enfermedad , MicroARNs , ARN Largo no Codificante , Humanos , Antígeno CD24/genética , Antígeno CD24/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Femenino , MicroARNs/genética , Animales , Ratones , ARN Largo no Codificante/genética , Ratones Desnudos , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Movimiento Celular/genética , Ratones Endogámicos BALB C , Pronóstico
12.
J Sex Marital Ther ; 50(6): 707-724, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38853443

RESUMEN

We investigated the effectiveness of online Sensate Focus exercises, delivered online as a series of 11 animation videos, in improving participants' sexual functioning and enhancing intimacy, relationship and sexual satisfaction. We studied 35 Chinese heterosexual couples, assessed them at pretest, post-test, and a three-month follow-up. Compared to the waitlist control group, the experimental group showed improvement in orgasm in women, and this was maintained at follow-up. Also, for those with a lower function at pretest, the intervention was possibly effective in improving erectile function among men, as well as overall sexual function and pain among women. These improvements were maintained at follow-up as well. Findings from the current study suggest that online Sensate Focus intervention has potential in treating sexual dysfunction of Chinese heterosexual couples. It may also serve as the first part of a stepped care approach or be integrated with other medication or cognitive behavioral therapy treatment.


Asunto(s)
Heterosexualidad , Humanos , Femenino , Masculino , Adulto , Heterosexualidad/psicología , China , Parejas Sexuales/psicología , Disfunciones Sexuales Psicológicas/terapia , Disfunciones Sexuales Psicológicas/psicología , Disfunciones Sexuales Fisiológicas/terapia , Disfunciones Sexuales Fisiológicas/psicología , Orgasmo , Conducta Sexual/psicología , Satisfacción Personal , Persona de Mediana Edad , Relaciones Interpersonales , Terapia de Parejas/métodos , Pueblos del Este de Asia
13.
Ageing Res Rev ; 99: 102363, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38838785

RESUMEN

The basolateral amygdala (BLA) is the subregion of the amygdala located in the medial of the temporal lobe, which is connected with a wide range of brain regions to achieve diverse functions. Recently, an increasing number of studies have focused on the participation of the BLA in many neuropsychiatric disorders from the neural circuit perspective, aided by the rapid development of viral tracing methods and increasingly specific neural modulation technologies. However, how to translate this circuit-level preclinical intervention into clinical treatment using noninvasive or minor invasive manipulations to benefit patients struggling with neuropsychiatric disorders is still an inevitable question to be considered. In this review, we summarized the role of BLA-involved circuits in neuropsychiatric disorders including Alzheimer's disease, perioperative neurocognitive disorders, schizophrenia, anxiety disorders, depressive disorders, posttraumatic stress disorders, autism spectrum disorders, and pain-associative affective states and cognitive dysfunctions. Additionally, we provide insights into future directions and challenges for clinical translation.


Asunto(s)
Trastornos Mentales , Humanos , Trastornos Mentales/fisiopatología , Trastornos Mentales/terapia , Animales , Complejo Nuclear Basolateral/fisiología , Complejo Nuclear Basolateral/fisiopatología
14.
Neuropharmacology ; 257: 110032, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38852839

RESUMEN

The full mechanism of action of propofol, a commonly administered intravenous anesthetic drug in clinical practice, remains elusive. The focus of this study was the role of GABAergic neurons which are the main neuron group in the ventral pallidum (VP) closely associated with anesthetic effects in propofol anesthesia. The activity of VP GABAergic neurons following propofol anesthesia in Vgat-Cre mice was observed via detecting c-Fos immunoreactivity by immunofluorescence and western blotting. Subsequently, chemogenetic techniques were employed in Vgat-Cre mice to regulate the activity of VP GABAergic neurons. The role of VP GABAergic neurons in generating the effects of general anesthesia induced by intravenous propofol was further explored through behavioral tests of the righting reflex. The results revealed that c-Fos expression in VP GABAergic neurons in Vgat-Cre mice dramatically decreased after propofol injection. Further studies demonstrated that chemogenetic activation of VP GABAergic neurons during propofol anesthesia shortened the duration of anesthesia and promoted wakefulness. Conversely, the inhibition of VP GABAergic neurons extended the duration of anesthesia and facilitated the effects of anesthesia. The results obtained in this study suggested that regulating the activity of GABAergic neurons in the ventral pallidum altered the effect of propofol on general anesthesia.


Asunto(s)
Anestesia General , Anestésicos Intravenosos , Prosencéfalo Basal , Neuronas GABAérgicas , Propofol , Propofol/farmacología , Neuronas GABAérgicas/efectos de los fármacos , Neuronas GABAérgicas/metabolismo , Animales , Prosencéfalo Basal/efectos de los fármacos , Anestésicos Intravenosos/farmacología , Anestesia General/métodos , Ratones , Masculino , Ratones Transgénicos , Proteínas Proto-Oncogénicas c-fos/metabolismo , Reflejo de Enderezamiento/efectos de los fármacos , Reflejo de Enderezamiento/fisiología , Vigilia/efectos de los fármacos , Vigilia/fisiología , Ratones Endogámicos C57BL , Proteínas del Transporte Vesicular de Aminoácidos Inhibidores
15.
J Hazard Mater ; 476: 135024, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-38943882

RESUMEN

The particle size distribution in tailings notably influences their physical properties and behavior. Despite this, our understanding of how the distribution of tailings particle sizes impacts in situ pollution and ecological remediation in in-situ environment remains limited. In this study, an iron tailings reservoir was sampled along a particle flow path to compare the pollution characteristic and microbial communities across regions with different particle sizes. The results revealed a gradual reduction in tailings particle size along the flow direction. The predominant mineral composition shifts from minerals such as albite and quartz to layered minerals. Total nitrogen, total organic carbon, and total metal concentrations increased, whereas the acid-generating potential decreased. The region with the finest tailings particle size exhibited the highest microbial diversity, featuring metal-resistant microorganisms such as KD4-96, Micrococcaceae, and Acidimicrobiia. Significant discrepancies were observed in tailings pollution and ecological risks across different particle sizes. Consequently, it is necessary to assess tailings reservoirs pollution in the early stages of remediation before determining appropriate remediation methods. These findings underscore that tailings particle distribution is a critical factor in shaping geochemical characteristics. The responsive nature of the microbial community further validated these outcomes and offered novel insights into the ecological remediation of tailings.

16.
Int J Mol Sci ; 25(11)2024 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-38891991

RESUMEN

The testes serve as the primary source of androgens and the site of spermatogenesis, with their development and function governed by hormonal actions via endocrine and paracrine pathways. Male fertility hinges on the availability of testosterone, a cornerstone of spermatogenesis, while follicle-stimulating hormone (FSH) signaling is indispensable for the proliferation, differentiation, and proper functioning of Sertoli and germ cells. This review covers the research on how androgens, FSH, and other hormones support processes crucial for male fertility in the testis and reproductive tract. These hormones are regulated by the hypothalamic-pituitary-gonad (HPG) axis, which is either quiescent or activated at different stages of the life course, and the regulation of the axis is crucial for the development and normal function of the male reproductive system. Hormonal imbalances, whether due to genetic predispositions or environmental influences, leading to hypogonadism or hypergonadism, can precipitate reproductive disorders. Investigating the regulatory network and molecular mechanisms involved in testicular development and spermatogenesis is instrumental in developing new therapeutic methods, drugs, and male hormonal contraceptives.


Asunto(s)
Espermatogénesis , Testículo , Humanos , Masculino , Testículo/metabolismo , Testículo/crecimiento & desarrollo , Animales , Hormona Folículo Estimulante/metabolismo , Sistema Hipotálamo-Hipofisario/metabolismo , Andrógenos/metabolismo , Testosterona/metabolismo
17.
Anal Chim Acta ; 1312: 342751, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38834265

RESUMEN

BACKGROUND: The abuse of the Phencyclidine-type substances, especially ketamine is a serious problem worldwide, and retrospective analysis are important for both the analysis and the identification of forms of drug abuse. The current major analytical methods, while all excellent in terms of accuracy, are time- and reagent-consuming. This depletion is made even more unfortunate by the fact that a large number of samples are negative in retrospective analyses. It is clear that a set of methods that can be analyzed both accurately and quickly need to be developed and applied to the screening and analysis of large quantities of samples. RESULTS: We described a urine test based on acoustic ejection mass spectrometry, which allows precise injection at very low volumes and near 1 ejection s-1 and data acquisition. The confidence in identification was increased by the characterization of the abundance ratio of the two pairs of ions. Urine samples could be diluted with water and loaded into a 384-well plate for sampling without complicated sample preparation. The sample in the transparent 384-well plate was pre-scanned by the laser, and then 20 nL droplets were ejected into the ion source for targeted analysis of 2 ion transitions per droplet totaling 9 targeted analytes in the sequence of acquisition methods. It took 90 min to screen 250 samples in this approach, yielding 10 ng mL-1 detection limits. Positive samples were further analyzed by UHPLC-MS/MS for confirmation and quantification of up to 36 analytes. SIGNIFICANCE: This was the first fast screening method for phencyclidine-type substances based on acoustic ejection mass spectrometry, which greatly reduces the analytical time, and can accomplish in 1.5 h what UHPLC-MS/MS needs 3 days to complete. And the samples can be analyzed without complicated sample preparation, and also can obtain good detectability. It was applied to a short-term retrospective analysis in Shanghai, and its accuracy was also extremely high.


Asunto(s)
Ensayos Analíticos de Alto Rendimiento , Fenciclidina , Espectrometría de Masas en Tándem , Espectrometría de Masas en Tándem/métodos , Fenciclidina/orina , Humanos , Detección de Abuso de Sustancias/métodos , Acústica
18.
Molecules ; 29(12)2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38930992

RESUMEN

In this study, RM (red mud) was acidified with sulfuric acid, and the acidified ARM (acidified red mud) was utilized as an innovative adsorption material for treating antibiotic-containing wastewater. The adsorption conditions, kinetics, isotherms, thermodynamics, and mechanism of ARM for CIP (ciprofloxacin) were investigated. The characterization of the ARM involved techniques such as scanning electron microscopy (SEM), transmission electron microscopy (TEM), Brunauer-Emmett-Teller (BET), X-ray diffraction (XRD), X-ray fluorescence (XRF), thermogravimetric analysis (TGA), and NH3-TPD analysis. Adsorption studies employed a response surface methodology (RSM) for the experimental design. The results showed that ARM can absorb CIP effectively. The RSM optimal experiment indicated that the most significant model terms influencing adsorption capacity were solution pH, CIP initial concentration, and ARM dosage, under which the predicted maximum adsorption capacity achieved 7.30 mg/g. The adsorption kinetics adhered to a pseudo-second-order model, while equilibrium data fitted the Langmuir-Freundlich isotherm, yielding maximum capacity values of 7.35 mg/g. The adsorption process occurred spontaneously and absorbed heat, evidenced by ΔGθ values between -83.05 and -91.50 kJ/mol, ΔSθ at 281.6 J/mol/K, and ΔHθ at 0.86 kJ/mol. Analysis using attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) indicated a complex reaction between the Al-O in the ARM and the ester group -COO in CIP. The C=O bond in CIP was likely to undergo a slight electrostatic interaction or be bound to the internal spherical surface of the ARM. The findings indicate that ARM is a promising and efficient adsorbent for CIP removal from wastewater.


Asunto(s)
Ciprofloxacina , Termodinámica , Contaminantes Químicos del Agua , Purificación del Agua , Adsorción , Ciprofloxacina/química , Contaminantes Químicos del Agua/química , Cinética , Purificación del Agua/métodos , Concentración de Iones de Hidrógeno , Aguas Residuales/química , Antibacterianos/química
19.
Adv Healthc Mater ; : e2401649, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38938121

RESUMEN

Immune checkpoint blockade (ICB) has significantly improved the prognosis of patients with cancer, although the majority of such patients achieve low response rates; consequently, new therapeutic approaches are urgently needed. The upregulation of sialic acid-containing glycans is a common characteristic of cancer-related glycosylation, which drives disease progression and immune escape via numerous pathways. Herein, the development of self-assembled core-shell nanoscale coordination polymer nanoparticles loaded with a sialyltransferase inhibitor, referred to as NCP-STI which effectively stripped diverse sialoglycans from cancer cells, providing an antibody-independent pattern to disrupt the emerging Siglec-sialic acid glyco-immune checkpoint is reported. Furthermore, NCP-STI inhibits sialylation of the concentrated nucleoside transporter 1 (CNT1), promotes the intracellular accumulation of anticancer agent gemcitabine (Gem), and enhances Gem-induced immunogenic cell death (ICD). As a result, the combination of NCP-STI and Gem (NCP-STI/Gem) evokes a robust antitumor immune response and exhibits superior efficacy in restraining the growth of multiple murine tumors and pulmonary metastasis. Collectively, the findings demonstrate a novel form of small molecule-based chemo-immunotherapy approach which features sialic acids blockade that enables cooperative effects of cancer cell chemosensitivity and antitumor immune responses for cancer treatment.

20.
World J Clin Cases ; 12(15): 2568-2577, 2024 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-38817233

RESUMEN

BACKGROUND: The measurement of triceps skinfold (TSF) thickness serves as a noninvasive metric for evaluating subcutaneous fat distribution. Despite its clinical utility, the TSF thickness trajectories and their correlation with overall mortality have not been thoroughly investigated. AIM: To explore TSF thickness trajectories of Chinese adults and to examine their associations with all-cause mortality. METHODS: This study encompassed a cohort of 14747 adults sourced from the China Health and Nutrition Survey. Latent class trajectory modeling was employed to identify distinct trajectories of TSF thickness. Subjects were classified into subgroups reflective of their respective TSF thickness trajectory. We utilized multivariate Cox regression analyses and mediation examinations to explore the link between TSF thickness trajectory and overall mortality, including contributory factors. RESULTS: Upon adjustment for multiple confounding factors, we discerned that males in the 'Class 2: Thin-stable' and 'Class 3: Thin-moderate' TSF thickness trajectories exhibited a markedly reduced risk of mortality from all causes in comparison to the 'Class 1: Extremely thin' subgroup. In the mediation analyses, the Geriatric Nutritional Risk Index was found to be a partial intermediary in the relationship between TSF thickness trajectories and mortality. For females, a lower TSF thickness pattern was significantly predictive of elevated all-cause mortality risk exclusively within the non-elderly cohort. CONCLUSION: In males and non-elderly females, lower TSF thickness trajectories are significantly predictive of heightened mortality risk, independent of single-point TSF thickness, body mass index, and waist circumference.

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