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The isocortex and hippocampal formation (HPF) in the mammalian brain play critical roles in perception, cognition, emotion, and learning. We profiled â¼1.3 million cells covering the entire adult mouse isocortex and HPF and derived a transcriptomic cell-type taxonomy revealing a comprehensive repertoire of glutamatergic and GABAergic neuron types. Contrary to the traditional view of HPF as having a simpler cellular organization, we discover a complete set of glutamatergic types in HPF homologous to all major subclasses found in the six-layered isocortex, suggesting that HPF and the isocortex share a common circuit organization. We also identify large-scale continuous and graded variations of cell types along isocortical depth, across the isocortical sheet, and in multiple dimensions in hippocampus and subiculum. Overall, our study establishes a molecular architecture of the mammalian isocortex and hippocampal formation and begins to shed light on its underlying relationship with the development, evolution, connectivity, and function of these two brain structures.
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Hipocampo/citología , Neocórtex/citología , Transcriptoma/genética , Animales , Neuronas GABAérgicas/citología , Neuronas GABAérgicas/metabolismo , Ácido Glutámico/metabolismo , Ratones Endogámicos C57BL , Ratones TransgénicosRESUMEN
BACKGROUND: Caffeic acid O-methyltransferase (COMT) is a key enzyme that regulates melatonin synthesis and is involved in regulating the growth, development, and response to abiotic stress in plants. Tea plant is a popular beverage consumed worldwide, has been used for centuries for its medicinal properties, including its ability to reduce inflammation, improve digestion, and boost immune function. By analyzing genetic variation within the COMT family, while helping tea plants resist adversity, it is also possible to gain a deeper understanding of how different tea varieties produce and metabolize catechins, then be used to develop new tea cultivars with desired flavor profiles and health benefits. RESULTS: In this study, a total of 25 CsCOMT genes were identified based on the high-quality tea (Camellia sinensis) plant genome database. Phylogenetic tree analysis of CsCOMTs with COMTs from other species showed that COMTs divided into four subfamilies (Class I, II, III, IV), and CsCOMTs was distributed in Class I, Class II, Class III. CsCOMTs not only undergoes large-scale gene recombination in pairs internally in tea plant, but also shares 2 and 7 collinear genes with Arabidopsis thaliana and poplar (Populus trichocarpa), respectively. The promoter region of CsCOMTs was found to be rich in cis-acting elements associated with plant growth and stress response. By analyzing the previously transcriptome data, it was found that some members of CsCOMT family exhibited significant tissue-specific expression and differential expression under different stress treatments. Subsequently, we selected six CsCOMTs to further validated their expression levels in different tissues organ using qRT-PCR. In addition, we silenced the CsCOMT19 through virus-induced gene silencing (VIGS) method and found that CsCOMT19 positively regulates the synthesis of melatonin in tea plant. CONCLUSION: These results will contribute to the understanding the functions of CsCOMT gene family and provide valuable information for further research on the role of CsCOMT genes in regulating tea plant growth, development, and response to abiotic stress.
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Camellia sinensis , Melatonina , Metiltransferasas , Camellia sinensis/fisiología , Melatonina/genética , Filogenia , Té , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
A novel category of asymmetric boron chromophores with the attachment of two BF2 moieties denoted as BOPAM, has been successfully synthesized via a one-pot three-step reaction starting from N-phenylbenzothioamide. This synthetic route results in the production of [a] and [b]benzo-fused BOPAMs along with post-functionalization of the [a]benzo-fused BOPAMs. The photophysical properties of these compounds have been systematically investigated through steady-state absorption and fluorescence emission measurements in solvents at both ambient and cryogenic temperatures, as well as in the solid state. Computational methods have been employed to elucidate the emissive characteristics of the benzo-fused BOPAMs, revealing distinctive photophysical attributes, including solvent-dependent fluorescence intensity. Remarkably, certain BOPAM derivatives exhibit noteworthy photophysical phenomena, such as the induction of off-on fluorescence emission under specific solvent conditions and the manifestation of intermolecular charge transfer states in solid-state matrices. Through post-functionalization strategies involving the introduction of electron-donating groups onto the [a]benzo-fused BOPAM scaffold, an intramolecular charge transfer (ICT) pathway is activated, leading to substantial fluorescence quenching via non-radiative decay processes. Notably, one [a]benzo-fused BOPAM variant exhibits a pronounced fluorescence enhancement upon exposure to acidic conditions, thereby underscoring its potential utility in pH-sensing applications.
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BACKGROUND: Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, Streptococcus pneumoniae and Staphylococcus aureus are major bacterial causes of lower respiratory tract infections (LRTIs) globally, leading to substantial morbidity and mortality. The rapid increase of antimicrobial resistance (AMR) in these pathogens poses significant challenges for their effective antibiotic therapy. In low-resourced settings, patients with LRTIs are prescribed antibiotics empirically while awaiting several days for culture results. Rapid pathogen and AMR gene detection could prompt optimal antibiotic use and improve outcomes. METHODS: Here, we developed multiplex quantitative real-time PCR using EvaGreen dye and melting curve analysis to rapidly identify six major pathogens and fourteen AMR genes directly from respiratory samples. The reproducibility, linearity, limit of detection (LOD) of real-time PCR assays for pathogen detection were evaluated using DNA control mixes and spiked tracheal aspirate. The performance of RT-PCR assays was subsequently compared with the gold standard, conventional culture on 50 tracheal aspirate and sputum specimens of ICU patients. RESULTS: The sensitivity of RT-PCR assays was 100% for K. pneumoniae, A. baumannii, P. aeruginosa, E. coli and 63.6% for S. aureus and the specificity ranged from 87.5% to 97.6%. The kappa correlation values of all pathogens between the two methods varied from 0.63 to 0.95. The limit of detection of target bacteria was 1600 CFU/ml. The quantitative results from the PCR assays demonstrated 100% concordance with quantitative culture of tracheal aspirates. Compared to culture, PCR assays exhibited higher sensitivity in detecting mixed infections and S. pneumoniae. There was a high level of concordance between the detection of AMR gene and AMR phenotype in single infections. CONCLUSIONS: Our multiplex quantitative RT-PCR assays are fast and simple, but sensitive and specific in detecting six bacterial pathogens of LRTIs and their antimicrobial resistance genes and should be further evaluated for clinical utility.
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Antibacterianos , Infecciones del Sistema Respiratorio , Humanos , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Escherichia coli/genética , Staphylococcus aureus/genética , Reproducibilidad de los Resultados , Reacción en Cadena de la Polimerasa Multiplex/métodos , Farmacorresistencia Bacteriana , Bacterias/genética , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/microbiología , Streptococcus pneumoniae/genética , Klebsiella pneumoniae/genéticaRESUMEN
The adsorption of organic compounds onto metal surfaces holds significant importance across various applications, where understanding the intricate interactions between the compounds and the metal surfaces is indispensable. By using density functional theory calculations, this study investigated the impact of functional groups on the interaction between the thione form of 2-mercaptobenzothiazole (MBT) and the Cu(111) surface. The results indicated that substituting functional groups at the C6 position exerts a dual influence on the covalent and non-covalent interactions (NCI). Electron-donating groups enhanced both covalent and non-covalent interactions, whereas electron-withdrawing groups decreased covalent while increasing non-covalent interactions. The covalent interaction between MBTs and Cu(111) is mainly governed by the electron donation from the occupied orbitals of the molecules to the conduction band of copper, with the absolute interaction energies (eV) increasing in the order of MBT-NO2 (0.629) < MBT-COOH (0.660) < MBT-Cl (0.699) < MBT (0.715) < MBT-SH (0.727) < MBT-OH (0.733) < MBT-CH3 (0.735) < MBT-OCH3 (0.749) < MBT-NH2 (0.781) < MBT-NHCH3 (0.792). The influence of functional groups on covalent interactions is clarified by examining changes in the molecule's electronic structure, revealing a linear relationship between covalent interaction energy and HOMO energy, or the Hammett substituent constant. However, the impact of functional groups on non-covalent interactions is more complex and cannot be described by changes in the electronic structure. A novel parameter, the substitution interaction energy, was proposed to capture the effect of functional groups on the NCI-included adsorption energy of MBT derivatives on the Cu(111) surface. The stronger the substitution interaction, the stronger the NCI-included interaction of MBTs on Cu(111). The absolute NCI-included interaction energies follow the order of MBT (2.141) < MBT-Cl (2.213) < MBT-COOH (2.266) < MBT-CH3 (2.294) < MBT-OH (2.331) < MBT-OCH3 (2.379) < MBT-NO2 (2.461) = MBT-NH2 (2.461) < MBT-SH (2.530) < MBT-NHCH3 (2.565). These insights offer valuable guidance for manipulating the adsorption of organic substances on metal surfaces through functional groups in diverse applications.
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Recently, deep-red-emitting phosphors that can be excited by ultraviolet (UV) and near-ultraviolet (NUV) light have been extensively investigated for plant growth LED applications. However, due to the harmful effects of these high-energy rays on plants, violet- or blue-excited deep-red-emitting phosphors are considered a more appropriate solution. In this work, SrAl12O19:Cr3+ phosphors were synthesized using a simple solid-state reaction, revealing a strikingly sharp deep-red emission band centered at 694 nm and effective excitation by violet light. The optimal SrAl12O19:1.0%Cr3+ phosphor, annealed at 1500°C, exhibits an extended lifetime of 0.549 ms, an energy activation level of 0.239 eV, a good quantum efficiency (QE) of 36.2%, and superior color purity at 100%. Further, an LED prototype with a precise absorption spectrum for far-red phytochrome (Pfr) has been demonstrated. These results indicate that the synthesized SrAl12O19:1.0%Cr3+ phosphors could be used as a promising deep-red-emitting phosphor for plant growth LED.
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Cromo , Cromo/química , Desarrollo de la Planta , Sustancias Luminiscentes/química , Sustancias Luminiscentes/síntesis química , Estroncio/químicaRESUMEN
PURPOSES: The objective of this research was to interpret and analyze the imaging, audiological features and cochlear implantation outcomes in cochlear nerve deficiency children. MATERIAL AND METHODS: Retrospective analysis. RESULTS: 25 prelingual hearing loss children diagnosed cochlear nerve deficiency (CND), the age range from 1 to 15 (mean age, 5.04), underwent cochlear implantation at Ear Nose and Throat Hospital - Ho Chi Minh City (ENT hospital - HCMC) from 2016 to 2023. All children had sensorineural hearing loss (SNHL) from severe to profound degree. Magnetic resonance imaging (MRI) showed cochlear nerve hypoplasia in 76 % and cochlear nerve aplasia in 24 % of cases. Inner ear malformations were found in 52 % of cases. The mean Categories of Auditory Performance (CAP) score at 1 year after surgery was 4.8. At 6 months and 1 year after surgery, the mean CAP score of the aplasia group was significantly lower than that of the hypoplasia group (p < 0.05). CONCLUSIONS: In cochlear nerve deficiency children, auditory perception and speech performance still improved after cochlear implantation. However, this progress was significantly limited in cochlear nerve aplasia group.
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OBJECTIVES: To evaluate a co-designed intervention using digital resources "Vietnam Cancer Caring Coping" (V-CCC) on the health literacy, depression, and quality of life of caregivers supporting a cancer patient in oncology hospitals in Vietnam. METHODS: A pre-post quantitative evaluation with adult cancer caregivers across regional Oncology hospitals in Vietnam (Ho Chi Minh City, Da Nang, Can Tho, and Hue). Participants completed baseline and follow-up measures of health literacy (HLS-SF12) depression (PHQ-9) and Health-related Quality of Life (5Q-5D-5L). Participants accessed and reviewed V-CCC for a 2-week period. RESULTS: Two hundred and thirty-four caregivers completed pre and post-tests. Most participants were female (n = 143, 61%), married (n = 165, 70%), aged 18-44 (n = 155, 66%), lived rurally (n = 157, 67%). All health literacy scores of participants in post-intervention were significantly higher than that in pre-intervention across all domain's healthcare, disease prevention, and health promotion as well as the total score (p < 0.001). A significant reduction in the proportion of caregivers reporting PHQ-9 moderately severe/severe depression post-intervention was demonstrated (10.2 vs. 6.1%, respectively (p ≤ 0.001). No significant differences were observed pre and post-intervention across four 5Q-5D-5L health dimensions: mobility, self-care, usual activities, and pain/discomfort. Regarding anxiety/depression as measured by 5Q-5D-5L the proportion of participants who reported having moderate, severe, and extreme problems in pre- and post-intervention was statistically significant (32 vs. 24%), respectively (p = 0.0028). CONCLUSION: Co-designed digital resources can reduce health literacy inequities and improve psychological outcomes for cancer caregivers.
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Pesticides are on the list of substances that are routinely monitored by agencies and organizations in various natural environments and habitats. Diazinon (DZN) is the active ingredient in more than 20 agricultural pesticides, it causes the most damage and has been prohibited in many countries around the world. The final product CoWO4/g-C3N4 Z-scheme heterojunction was successfully synthesized in this work, where CoWO4 nanoparticles were deposited on the surface of g-C3N4. CoWO4/g-C3N4 structure allowed for the efficient separation of photo-generated electron-hole pairs, with electrons at the CoWO4 CB migrating to the g-C3N4 VB and preserving the electrons at the g-C3N4 CB and holes in the CoWO4 VB. The photodegradation efficiency of DZN using CoWO4/g-C3N4 Z-scheme heterojunction was investigated, as compared with its precursors, such as CoWO4, and g-C3N4. CoWO4/g-C3N4 Z-scheme heterojunction demonstrated the highest degradation capacity for DZN removal. Based on the results, the photocatalysis of the CoWO4/g-C3N4 Z-scheme heterojunction can be recycled for the effective removal of DZN by simple washing after three runs, proving the heterojunction's stability and suggesting CoWO4 as a promising material for the removal of DZN from contaminated water sources.
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Diazinón , Plaguicidas , Peróxido de Hidrógeno , Fotólisis , AgriculturaRESUMEN
The SPOT-MAS assay "Screening for the Presence Of Tumor by Methylation And Size" detects the five most common cancers in Vietnam by evaluating circulating tumor DNA in the blood. Here, we validated its performance in a prospective multi-center clinical trial, K-DETEK. Our analysis of 2795 participants from 14 sites across Vietnam demonstrates its ability to detect cancers in asymptomatic individuals with a positive predictive value of 60%, with 83.3% accuracy in detecting tumor location. We present a case report to support further using SPOT-MAS as a complementary method to achieve early cancer detection and provide the opportunity for early treatment.
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BACKGROUND: To investigate the mechanism of RNA silencing suppression, the genetic transformation of viral suppressors of RNA silencing (VSRs) in Arabidopsis integrates ectopic VSR expression at steady state, which overcomes the VSR variations caused by different virus infections or limitations of host range. Moreover, identifying the insertion of the transgenic VSR gene is necessary to establish a model transgenic plant for the functional study of VSR. METHODS: Developing an endogenous AGO1-based in vitro RNA-inducing silencing complex (RISC) assay prompts further investigation into VSR-mediated suppression. Three P1/HC-Pro plants from turnip mosaic virus (TuMV) (P1/HC-ProTu), zucchini yellow mosaic virus (ZYMV) (P1/HC-ProZy), and tobacco etch virus (TEV) (P1/HC-ProTe) were identified by T-DNA Finder and used as materials for investigations of the RISC cleavage efficiency. RESULTS: Our results indicated that the P1/HC-ProTu plant has slightly lower RISC activity than P1/HC-ProZy plants. In addition, the phenomena are consistent with those observed in TuMV-infected Arabidopsis plants, which implies that HC-ProTu could directly interfere with RISC activity. CONCLUSIONS: In this study, we demonstrated the application of various plant materials in an in vitro RISC assay of VSR-mediated RNA silencing suppression.
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Arabidopsis , Potyvirus , Interferencia de ARN , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas Virales/genética , Proteínas Virales/metabolismo , Potyvirus/genética , Nicotiana , Enfermedades de las PlantasRESUMEN
This review presents a robust strategy to design photosensitizers (PSs) for various species. Photodynamic therapy (PDT) is a photochemical-based treatment approach that involves the use of light combined with a light-activated chemical, referred to as a PS. Attractively, PDT is one of the alternatives to conventional cancer treatment due to its noninvasive nature, high cure rates, and low side effects. PSs play an important factor in photoinduced reactive oxygen species (ROS) generation. Although the concept of photosensitizer-based photodynamic therapy has been widely adopted for clinical trials and bioimaging, until now, to our surprise, there has been no relevant review article on rational designs of organic PSs for PDT. Furthermore, most of published review articles in PDT focused on nanomaterials and nanotechnology based on traditional PSs. Therefore, this review aimed at reporting recent strategies to develop innovative organic photosensitizers for enhanced photodynamic therapy, with each example described in detail instead of providing only a general overview, as is typically done in previous reviews of PDT, to provide intuitive, vivid, and specific insights to the readers.
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Neoplasias , Fotoquimioterapia , Humanos , Nanotecnología , Neoplasias/tratamiento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Especies Reactivas de OxígenoRESUMEN
BACKGROUND: Little information is available on the costs of respiratory syncytial virus (RSV) in Vietnam or other low- and middle-income countries. Our study estimated the costs of LRTIs associated with RSV infection among children in southern Vietnam. METHODS: We conducted a prospective cohort study evaluating household and societal costs associated with LRTIs stratified by RSV status and severity among children under 2 years old who sought care at a major pediatric referral hospital in southern Vietnam. Enrollment periods were September 2019-December 2019, October 2020-June 2021 and October 2021-December 2021. RSV status was confirmed by a validated RT-PCR assay. RSV rapid detection antigen (RDA) test performance was also evaluated. Data on resource utilization, direct medical and non-medical costs, and indirect costs were collected from billing records and supplemented by patient-level questionnaires. All costs are reported in 2022 US dollars. RESULTS: 536 children were enrolled in the study, with a median age of 7 months (interquartile range [IQR] 3-12). This included 210 (39.2%) children from the outpatient department, 318 children (59.3%) from the inpatient respiratory department (RD), and 8 children (1.5%) from the intensive care unit (ICU). Nearly 20% (105/536) were RSV positive: 3.9 percent (21/536) from the outpatient department, 15.7% (84/536) from the RD, and none from the ICU. The median total cost associated with LRTI per patient was US$52 (IQR 32-86) for outpatients and US$184 (IQR 109-287) for RD inpatients. For RSV-associated LRTIs, the median total cost per infection episode per patient was US$52 (IQR 32-85) for outpatients and US$165 (IQR 95-249) for RD inpatients. Total out-of-pocket costs of one non-ICU admission of RSV-associated LRTI ranged from 32%-70% of the monthly minimum wage per person (US$160) in Ho Chi Minh City. The sensitivity and the specificity of RSV RDA test were 88.2% (95% CI 63.6-98.5%) and 100% (95% CI 93.3-100%), respectively. CONCLUSION: These are the first data reporting the substantial economic burden of RSV-associated illness in young children in Vietnam. This study informs policymakers in planning health care resources and highlights the urgency of RSV disease prevention.
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Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Infecciones del Sistema Respiratorio , Niño , Humanos , Lactante , Preescolar , Infecciones por Virus Sincitial Respiratorio/epidemiología , Estudios de Cohortes , Estudios Prospectivos , Vietnam/epidemiología , Estrés Financiero , Virus Sincitial Respiratorio Humano/genética , HospitalizaciónRESUMEN
The aim of this study is to analyse the changing patterns in the transmission of COVID-19 in relation to changes in Vietnamese governmental policies, based on epidemiological data and policy actions in a large Vietnamese province, Bac Ninh, in 2021. Data on confirmed cases from January to December 2021 were collected, together with policy documents. There were three distinct periods of the COVID-19 pandemic in Bac Ninh province during 2021. During the first period, referred to as the 'Zero-COVID' period (01/04-07/04/2021), there was a low population vaccination rate, with less than 25% of the population receiving its first vaccine dose. Measures implemented during this period focused on domestic movement restrictions, mask mandates, and screening efforts to control the spread of the virus. The subsequent period, referred to as the 'Transition' period (07/05-10/22/2021), witnessed a significant increase in population vaccination coverage, with 80% of the population receiving their first vaccine dose. During this period, several days passed without any reported COVID-19 cases in the community. The local government implemented measures to manage domestic actions and reduce the time spent in quarantine, and encouraged home quarantining for the close contacts of cases with COVID-19. Finally, the 'New-normal' stage (10/23-12/31/2021), during which the population vaccination coverage with a second vaccine dose increased to 70%, and most of the mandates for the prevention and control of COVID-19 were reduced. In conclusion, this study highlights the importance of governmental policies in managing and controlling the transmission of COVID-19 and provides insights for developing realistic and context-specific strategies in similar settings.
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COVID-19 , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Pandemias/prevención & control , Cuarentena , SARS-CoV-2 , Vietnam/epidemiologíaRESUMEN
Combination of high quality cavity such as glass microsphere and emitting nano-particle coating layers can create novel strongly emitting devices. Herein, we demonstrate an erbium-doped silica microsphere coated by dual-emission carbon quantum dots, which have the sizes of 3-5 nm, emitting green up-conversion with narrow line-width green light at wavelength of 537 nm. The dual-emission carbon quantum dots fabricated by hydrothermal process and have luminescent emission wavelengths in the range of 410-550 nm. The carbon quantum dot coated erbium silica microsphere is pumped at wavelength of 976 nm through the optical fibre on which microsphere attached on the tip. The dual-emission carbon quantum dot layers attributed to the strong green up-conversion light enhancement similar coated noble metallic thin films, however the light enhancement from dual-emission carbon quantum dot coated erbium silica microsphere depended on the thickness of coating layers. This result is useful for making visible emitting micro-devices and photonic integrated circuits.
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This study aimed to develop an extremely highly porous activated carbon derived from soybean curd residues (SCB-AC) through two-step pyrolyzing coupled with KOH activating process and then apply it for removing paracetamol (PRC) and tetracycline (TCH) from water. The optimal conditions for chemical activation were 800 °C and the ratio of KOH to material (4/1; wt./wt.). SCB-AC adsorbents (before and after adsorption) were characterized by Brunauer-Emmet-Teller (BET) analyser, Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy, and Raman spectroscopy. Adsorption kinetics, isotherm, and thermodynamics were concluded under batch experiments. The effects of pH (2-10) and NaCl (0-1 M) on adsorption processes were investigated. Reusable properties of laden SCB-AC were evaluated by studying desorption and cycles of adsorption/desorption. Results indicated that SCB-AC exhibited a large specific surface area (3306 m2/g) and high total pore volume (2.307 cm3/g), with mesoporous volume accounting for 86.9%. Its porosity characteristics (average pore width: 2.725 nm) are very appropriate for adsorbing two pharmaceuticals through pore-filling mechanism. Adsorption processes were less affected by the parameters: pH, NaCl, and water matrixes. The kinetics for adsorbing PRC reached a faster equilibrium than that for TCH. The Langmuir maximum adsorption capacity of SCB-AC (pHeq 7.0 and 25 °C) was 1235 mg/g (for adsorbing TCH) and 646 mg/g (PRC). Pore filling (confirmed by BET analyser) and π-π interaction (confirmed by FTIR and Raman spectroscopy) were dominant adsorption mechanisms. Those mechanisms were physisorption (ΔH° = 13.71 and -21.04 kJ/mol for adsorbing TCH and PRC, respectively). SCB-AC can serve as an outstanding material for removing pharmaceuticals from water.
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Acetaminofén , Contaminantes Químicos del Agua , Adsorción , Cloruro de Sodio , Contaminantes Químicos del Agua/análisis , Tetraciclina , Antibacterianos , Termodinámica , Cinética , Espectroscopía Infrarroja por Transformada de Fourier , Preparaciones Farmacéuticas , Concentración de Iones de HidrógenoRESUMEN
BACKGROUND: Research evidence shows a strong association between adverse childhood experiences (ACEs) and later-life substance use. But little is known about the prevalence and impact of ACEs among young people using drugs (YPUD) in Vietnam. METHOD: A cross-sectional study using respondent-driven sampling and peer recruitment methods was conducted among YPUD aged 16-24 in three cities in Vietnam. Eligible participants were screened for ACEs using the ACE-IQ, tested for HIV and hepatitis C, and assessed for sociodemographic and behavioral characteristics. RESULTS: Data were collected on 553 individuals whose median age was 20: 79% were male, 18.3% women and 2.7% transgender. Methamphetamine use was reported by 75.8% of participants. 85.5% reported at least one ACE and 27.5% had four ACEs or more. An ACE score of 4 or higher was associated with female and transgender, lower educational level, methamphetamine use, buying sex, depression, psychotic symptoms and expressed need for mental health support. CONCLUSIONS: ACEs were found to be very common among YPUD in Vietnam. It is therefore strongly recommended that these young people should be provided with a comprehensive and secure assessment and care that includes not only essential harm reduction and addiction treatment needs but also addresses their mental health needs.
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Experiencias Adversas de la Infancia , Metanfetamina , Humanos , Masculino , Femenino , Adolescente , Adulto Joven , Adulto , Estudios Transversales , Vietnam/epidemiología , Salud Mental , Metanfetamina/efectos adversosRESUMEN
Small heat shock proteins (sHSPs) are a class of ATP-independent molecular chaperones that play vital roles in maintaining protein solubility and preventing aberrant protein aggregation. They form highly dynamic, polydisperse oligomeric ensembles and contain long intrinsically disordered regions. Experimental challenges posed by these properties have greatly impeded our understanding of sHSP structure and mechanism of action. Here we characterize interactions between the human sHSP HspB1 (Hsp27) and microtubule-associated protein tau, which is implicated in multiple dementias, including Alzheimer's disease. We show that tau binds both to a well-known binding groove within the structured alpha-crystallin domain (ACD) and to sites within the enigmatic, disordered N-terminal region (NTR) of HspB1. However, only interactions involving the NTR lead to productive chaperone activity, whereas ACD binding is uncorrelated with chaperone function. The tau-binding groove in the ACD also binds short hydrophobic regions within HspB1 itself, and HspB1 mutations that disrupt these intrinsic ACD-NTR interactions greatly enhance chaperone activity toward tau. This leads to a mechanism in which the release of the disordered NTR from a binding groove on the ACD enhances chaperone activity toward tau. The study advances understanding of the mechanisms by which sHSPs achieve their chaperone activity against amyloid-forming clients and how cells defend against pathological tau aggregation. Furthermore, the resulting mechanistic model points to ways in which sHSP chaperone activity may be increased, either by native factors within the cell or by therapeutic intervention.
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Proteínas de Choque Térmico/química , Proteínas de Choque Térmico/metabolismo , Chaperonas Moleculares/química , Chaperonas Moleculares/metabolismo , Proteínas tau/metabolismo , Proteínas de Choque Térmico/genética , Humanos , Modelos Moleculares , Chaperonas Moleculares/genética , Unión Proteica , Dominios Proteicos , alfa-Cristalinas/metabolismo , Proteínas tau/genéticaRESUMEN
Ciprofloxacin (CFX) and ofloxacin (OFX) are commonly found as residual contaminants in aquatic environments, posing potential risks to various species. To ensure the safety of aquatic wildlife, it is essential to determine the toxicity of these antibiotics and establish appropriate concentration limits. Additionally, in (eco)toxicological studies, addressing the issue of multiple hypothesis testing through p-value adjustments is crucial for robust decision-making. In this study, we assessed the no observed adverse effect concentration (NOAEC) of CFX and OFX on Moina macrocopa across a concentration range of 0-400 µg L-1. Furthermore, we investigated multiple p-value adjustments to determine the NOAECs. Our analysis yielded consistent results across seven different p-value adjustments, indicating NOAECs of 100 µg CFX L-1 for age at first reproduction and 200 µg CFX L-1 for fertility. For OFX treatment, a NOAEC of 400 µg L-1 was observed for both biomarkers. However, further investigation is required to establish the NOAEC of OFX at higher concentrations with greater certainty. Our findings demonstrate that CFX exhibits higher toxicity compared to OFX, consistent with previous research. Moreover, this study highlights the differential performance of p-value adjustment methods in terms of maintaining statistical power while controlling the multiplicity problem, and their practical applicability. The study emphasizes the low NOAECs for these antibiotics in the zooplanktonic group, highlighting their significant risks to ecological and environmental safety. Additionally, our investigation of p-value adjustment approaches contributes to a deeper understanding of their performance characteristics, enabling (eco)toxicologists to select appropriate methods based on their specific needs and priorities.
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BACKGROUND: The use of intracytoplasmic sperm injection has increased substantially worldwide, primarily in couples with non-male factor infertility. However, there is a paucity of evidence from randomised trials supporting this approach compared with conventional in-vitro fertilisation (IVF). We aimed to investigate whether intracytoplasmic sperm injection would result in a higher livebirth rate compared with conventional IVF. METHODS: This open-label, multicentre, randomised trial was done at two IVF centres in Ho Chi Minh City, Vietnam (IVFMD, My Duc Hospital and IVFAS, An Sinh Hospital). Eligible couples were aged at least 18 years and the male partner's sperm count and motility (progressive motility) were normal based on WHO 2010 criteria. Couples had to have undergone two or fewer previous conventional IVF or intracytoplasmic sperm injection attempts, have used an antagonist protocol for ovarian stimulation, and agree to have two or fewer embryos transferred. Couples were randomly assigned (1:1) to undergo either intracytoplasmic sperm injection or conventional IVF, using block randomisation with variable block size of 2, 4, or 8 and a telephone-based central randomisation method. The computer-generated randomisation list was prepared by an independent statistician who had no other involvement in the study. Embryologists and couples were not masked to study groups because of the type of interventions and differences in hospital fees, but clinicians performing embryo transfer were unaware of study group allocation. The primary outcome was livebirth after the first embryo transfer from the initiated cycle. Analyses were done on an intention-to-treat basis. The trial is registered with ClinicalTrials.gov, NCT03428919. FINDINGS: Between March 16, 2018, and Aug 12, 2019, we randomly assigned 1064 couples to intracytoplasmic sperm injection (n=532) or conventional IVF (n=532). Livebirth after the first embryo transfer from the initiated cycle occurred in 184 (35%) of 532 couples randomly assigned to intracytoplasmic sperm injection and in 166 (31%) of 532 couples randomly assigned to conventional IVF (absolute difference 3·4%, 95% CI -2·4 to 9·2; risk ratio [RR] 1·11, 95% CI 0·93 to 1·32; p=0·27). 29 (5%) couples in the intracytoplasmic sperm injection group and 34 (6%) couples in the conventional IVF group had fertilisation failure (absolute difference -0·9%, -4·0 to 2·1, RR 0·85, 95% CI 0·53 to 1·38; p=0·60). INTERPRETATION: In couples with infertility in whom the male partner has a normal total sperm count and motility, intracytoplasmic sperm injection did not improve the livebirth rate compared with conventional IVF. Our results challenge the value of the routine use of intracytoplasmic sperm injection in assisted reproduction techniques for this population. FUNDING: My Duc Hospital and Merck Sharp and Dohme.