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1.
Nat Med ; 30(4): 944-945, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38641743
2.
Int J Parasitol Drugs Drug Resist ; 25: 100539, 2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38621317

RESUMO

Infection with Plasmodium falciparum is often deadly when it results in cerebral malaria, which is associated with neuropathology described as an overwhelming inflammatory response and mechanical obstruction of cerebral microvascular. PI3Kγ is a critical component of intracellular signal transduction and plays a central role in regulating cell chemotaxis, migration, and activation. The purpose of this study was to examine the relationship between inhibiting the PI3Kγ pathway and the outcome of experimental cerebral malaria (ECM) in C57BL/6J mice infected with the mouse malaria parasite, Plasmodium berghei ANKA. We observed that oral administration of the PI3Kγ inhibitor IPI549 after infection completely protected mice from ECM. IPI549 treatment significantly dampened the magnitude of inflammatory responses, with reduced production of pro-inflammatory factors, decreased T cell activation, and altered differentiation of antigen-presenting cells. IPI549 treatment protected the infected mice from neuropathology, as assessed by an observed reduction of pathogenic T cells in the brain. Treating the infected mice with IPI549 three days after parasite inoculation improved the murine blood brain barrier (BBB) integrity and helped the mice pass the onset of ECM. Together, these data indicate that oral administration of the PI3Kγ inhibitor IPI549 has a suppressive role in host inflammation and alleviates cerebral pathology, which supports IPI549 as a new malaria treatment option with potential therapeutic implications for cerebral malaria.

3.
J Med Internet Res ; 26: e56883, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38640480

RESUMO

BACKGROUND: With the rapid aging of the global population, the prevalence of mild cognitive impairment (MCI) and dementia is anticipated to surge worldwide. MCI serves as an intermediary stage between normal aging and dementia, necessitating more sensitive and effective screening tools for early identification and intervention. The BrainFx SCREEN is a novel digital tool designed to assess cognitive impairment. This study evaluated its efficacy as a screening tool for MCI in primary care settings, particularly in the context of an aging population and the growing integration of digital health solutions. OBJECTIVE: The primary objective was to assess the validity, reliability, and applicability of the BrainFx SCREEN (hereafter, the SCREEN) for MCI screening in a primary care context. We conducted an exploratory study comparing the SCREEN with an established screening tool, the Quick Mild Cognitive Impairment (Qmci) screen. METHODS: A concurrent mixed methods, prospective study using a quasi-experimental design was conducted with 147 participants from 5 primary care Family Health Teams (FHTs; characterized by multidisciplinary practice and capitated funding) across southwestern Ontario, Canada. Participants included health care practitioners, patients, and FHT administrative executives. Individuals aged ≥55 years with no history of MCI or diagnosis of dementia rostered in a participating FHT were eligible to participate. Participants were screened using both the SCREEN and Qmci. The study also incorporated the Geriatric Anxiety Scale-10 to assess general anxiety levels at each cognitive screening. The SCREEN's scoring was compared against that of the Qmci and the clinical judgment of health care professionals. Statistical analyses included sensitivity, specificity, internal consistency, and test-retest reliability assessments. RESULTS: The study found that the SCREEN's longer administration time and complex scoring algorithm, which is proprietary and unavailable for independent analysis, presented challenges. Its internal consistency, indicated by a Cronbach α of 0.63, was below the acceptable threshold. The test-retest reliability also showed limitations, with moderate intraclass correlation coefficient (0.54) and inadequate κ (0.15) values. Sensitivity and specificity were consistent (63.25% and 74.07%, respectively) between cross-tabulation and discrepant analysis. In addition, the study faced limitations due to its demographic skew (96/147, 65.3% female, well-educated participants), the absence of a comprehensive gold standard for MCI diagnosis, and financial constraints limiting the inclusion of confirmatory neuropsychological testing. CONCLUSIONS: The SCREEN, in its current form, does not meet the necessary criteria for an optimal MCI screening tool in primary care settings, primarily due to its longer administration time and lower reliability. As the number of digital health technologies increases and evolves, further testing and refinement of tools such as the SCREEN are essential to ensure their efficacy and reliability in real-world clinical settings. This study advocates for continued research in this rapidly advancing field to better serve the aging population. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/25520.


Assuntos
Disfunção Cognitiva , Demência , Humanos , Feminino , Idoso , Masculino , Demência/psicologia , Psicometria , Reprodutibilidade dos Testes , Estudos Prospectivos , Testes Neuropsicológicos , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Sensibilidade e Especificidade , Ontário
4.
Adv Sci (Weinh) ; : e2310115, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38491872

RESUMO

In this work, 2D ferromagnetic M3 GeTe2 (MGT, M = Ni/Fe) nanosheets with rich atomic Te vacancies (2D-MGTv ) are demonstrated as efficient OER electrocatalyst via a general mechanical exfoliation strategy. X-ray absorption spectra (XAS) and scanning transmission electron microscope (STEM) results validate the dominant presence of metal-O moieties and rich Te vacancies, respectively. The formed Te vacancies are active for the adsorption of OH* and O* species while the metal-O moieties promote the O* and OOH* adsorption, contributing synergistically to the faster oxygen evolution kinetics. Consequently, 2D-Ni3 GeTe2v exhibits superior OER activity with only 370 mV overpotential to reach the current density of 100 mA cm-2 and turnover frequency (TOF) value of 101.6 s-1 at the overpotential of 200 mV in alkaline media. Furthermore, a 2D-Ni3 GeTe2v -based anion-exchange membrane (AEM) water electrolysis cell (1 cm2 ) delivers a current density of 1.02 and 1.32 A cm-2 at the voltage of 3 V feeding with 0.1 and 1 m KOH solution, respectively. The demonstrated metal-O coordination with abundant atomic vacancies for ferromagnetic M3 GeTe2 and the easily extended preparation strategy would enlighten the rational design and fabrication of other ferromagnetic materials for wider electrocatalytic applications.

5.
Aging (Albany NY) ; 16(7): 5887-5904, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38517396

RESUMO

Acute kidney injury (AKI) is associated with immune cell activation and inflammation. However, the putative pathogenic mechanisms of this injury have not been thoroughly investigated. Natural killer (NK) cells play an important role in immune regulation; however, whether NK cells regulate AKI remains unclear. Cordyceps sinensis (CS), a modern Chinese patented medicine preparation, has been widely used in treating patients with chronic kidney disease (CKD) owing to its anti-inflammatory effects and maintenance of immune homeostasis. Whether 2'-deoxyadenosine, a major active component in CS, can ameliorate renal AKI by regulating immunity, particularly in NK cells, has not been reported. This study is the first to demonstrate how NK cells promote AKI by releasing perforin, interferon-gamma (IFN-γ) and other inflammatory factors in vivo and in vitro. Differential gene expression between AKI and normal tissues was assessed using bioinformatic analyses. Quantitative real-time PCR, western blotting, and immunohistochemical staining were used to detect target protein mRNA and protein expression. Levels of inflammatory factors were measured using enzyme-linked immunosorbent assay. We found the high doses of the 2'-deoxyadenosine treatment significantly alleviated FA-induced renal damage in vivo, and alleviated the NK cells of renal injury by activating the STING/IRF3 pathway to inhibit perforin release in vitro. The results showed that 2'-deoxyadenosine could mitigate AKI by downregulating the activity of NK cells (by decreasing the expressions of perforin and IFN-γ) and inhibiting the stimulator of interferon genes and phosphorylated IFN regulatory factor 3. This may provide valuable evidence supporting the clinical use of CS in treating patients with AKI.


Assuntos
Injúria Renal Aguda , Cordyceps , Fator Regulador 3 de Interferon , Células Matadoras Naturais , Proteínas de Membrana , Perforina , Transdução de Sinais , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/prevenção & controle , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/metabolismo , Animais , Cordyceps/química , Perforina/metabolismo , Fator Regulador 3 de Interferon/metabolismo , Camundongos , Transdução de Sinais/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Masculino , Interferon gama/metabolismo , Camundongos Endogâmicos C57BL
6.
Nutrients ; 16(4)2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38398816

RESUMO

Objective: the aim of this study was to identify plasma metabolomic markers of Dietary Approaches to Stop Hypertension (DASH) dietary patterns in pregnant women. Methods: This study included 186 women who had both dietary intake and metabolome measured from a nested case-control study within the NICHD Fetal Growth Studies-Singletons cohort (FGS). Dietary intakes were ascertained at 8-13 gestational weeks (GW) using the Food Frequency Questionnaire (FFQ) and DASH scores were calculated based on eight food and nutrient components. Fasting plasma samples were collected at 15-26 GW and untargeted metabolomic profiling was performed. Multivariable linear regression models were used to examine the association of individual metabolites with the DASH score. Least absolute shrinkage and selection operator (LASSO) regression was used to select a panel of metabolites jointly associated with the DASH score. Results: Of the total 460 known metabolites, 92 were individually associated with DASH score in linear regressions, 25 were selected as a panel by LASSO regressions, and 18 were identified by both methods. Among the top 18 metabolites, there were 11 lipids and lipid-like molecules (i.e., TG (49:1), TG (52:2), PC (31:0), PC (35:3), PC (36:4) C, PC (36:5) B, PC (38:4) B, PC (42:6), SM (d32:0), gamma-tocopherol, and dodecanoic acid), 5 organic acids and derivatives (i.e., asparagine, beta-alanine, glycine, taurine, and hydroxycarbamate), 1 organic oxygen compound (i.e., xylitol), and 1 organoheterocyclic compound (i.e., maleimide). Conclusions: our study identified plasma metabolomic markers for DASH dietary patterns in pregnant women, with most of being lipids and lipid-like molecules.


Assuntos
Abordagens Dietéticas para Conter a Hipertensão , Hipertensão , Humanos , Feminino , Gravidez , Abordagens Dietéticas para Conter a Hipertensão/métodos , Gestantes , 60408 , Estudos de Casos e Controles , Lipídeos , Biomarcadores
7.
Adv Mater ; : e2312207, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38329004

RESUMO

Linearly interlinked single atoms offer unprecedented physiochemical properties, but their synthesis for practical applications still poses significant challenges. Herein, linearly interlinked iron single-atom catalysts that are loaded onto interconnected carbon channels as cathodic sulfur hosts for room-temperature sodium-sulfur batteries are presented. The interlinked iron single-atom exhibits unique metallic iron bonds that facilitate the transfer of electrons to the sulfur cathode, thereby accelerating the reaction kinetics. Additionally, the columnated and interlinked carbon channels ensure rapid Na+ diffusion kinetics to support high-rate battery reactions. By combining the iron atomic chains and the topological carbon channels, the resulting sulfur cathodes demonstrate effective high-rate conversion performance while maintaining excellent stability. Remarkably, even after 5000 cycles at a current density of 10 A g-1 , the Na-S battery retains a capacity of 325 mAh g-1 . This work can open a new avenue in the design of catalysts and carbon ionic channels, paving the way to achieve sustainable and high-performance energy devices.

8.
Angew Chem Int Ed Engl ; 63(9): e202317941, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38197798

RESUMO

Wadsley-Roth niobium oxide phases have attracted extensive research interest recently as promising battery anodes. We have synthesized the niobium-molybdenum oxide shear phase (Nb, Mo)13 O33 with superior electrochemical Li-ion storage performance, including an ultralong cycling lifespan of at least 15000 cycles. During electrochemical cycling, a reversible single-phase solid-solution reaction with lithiated intermediate solid solutions is demonstrated using in situ X-ray diffraction, with the valence and short-range structural changes of the electrode probed by in situ Nb and Mo K-edge X-ray absorption spectroscopy. This work reveals that the superior stability of niobium molybdenum oxides is underpinned by changes in octahedral distortion during electrochemical reactions, and we report an in-depth understanding of how this stabilizes the oxide structure during cycling with implications for future long-life battery material design.

9.
Nat Ecol Evol ; 8(2): 229-238, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38168941

RESUMO

A steady rise in fires in the Western United States, coincident with intensifying droughts, imparts substantial modifications to the underlying vegetation, hydrology and overall ecosystem. Drought can compound the ecosystem disturbance caused by fire, although how these compound effects on hydrologic and ecosystem recovery vary among ecosystems is poorly understood. Here we use remote sensing-derived high-resolution evapotranspiration (ET) estimates from before and after 1,514 fires to show that ecoregions dominated by grasslands and shrublands are more susceptible to drought, which amplifies fire-induced ET decline and, subsequently, shifts water flux partitioning. In contrast, severely burned forests recover from fire slowly or incompletely, but are less sensitive to dry extremes. We conclude that moisture limitation caused by droughts influences the dynamics of water balance recovery in post-fire years. This finding explains why moderate to extreme droughts aggravate impacts on the water balance in non-forested vegetation, while moisture accessed by deeper roots in forests helps meet evaporative demands unless severe burns disrupt internal tree structure and deplete fuel load availability. Our results highlight the dominant control of drought on altering the resilience of vegetation to fires, with critical implications for terrestrial ecosystem stability in the face of anthropogenic climate change in the West.


Assuntos
Ecossistema , Incêndios , Estados Unidos , Secas , Florestas , Água
10.
Proc Natl Acad Sci U S A ; 121(2): e2304406120, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38181057

RESUMO

Despite a sea of interpretability methods that can produce plausible explanations, the field has also empirically seen many failure cases of such methods. In light of these results, it remains unclear for practitioners how to use these methods and choose between them in a principled way. In this paper, we show that for moderately rich model classes (easily satisfied by neural networks), any feature attribution method that is complete and linear-for example, Integrated Gradients and Shapley Additive Explanations (SHAP)-can provably fail to improve on random guessing for inferring model behavior. Our results apply to common end-tasks such as characterizing local model behavior, identifying spurious features, and algorithmic recourse. One takeaway from our work is the importance of concretely defining end-tasks: Once such an end-task is defined, a simple and direct approach of repeated model evaluations can outperform many other complex feature attribution methods.

11.
Sci Rep ; 14(1): 614, 2024 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-38182725

RESUMO

Obesity and type 2 diabetes mellitus (T2DM) is an alarming problem globally and a growing epidemic. Metabolic surgery has been shown to be successful in treating both obesity and T2DM, usually after other treatments have failed. This study aims to compare Roux-Y gastric bypass and sleeve gastrectomy in determining early diabetic outcomes in obese Malaysian patients with T2DM following surgery. A total of 172 obese patients with T2DM who were assigned to either laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) were analysed up to a year post-procedure. The patients' T2DM severity were stratified using the Individualized Metabolic Surgery (IMS) score into mild, moderate and severe. Remission rates of diabetes were compared between surgical techniques and within diabetic severity categories. T2DM remission for patients who underwent either surgical technique for mild, moderate or severe disease was 92.9%, 56.2% and 14.7% respectively. Both surgical techniques improved T2DM control for patients in the study. Comparing baseline with results 1 year postoperatively, median HbA1c reduced from 7.40% (IQR 2.60) to 5.80% (IQR 0.80) (p < 0.001), mean total antidiabetic medications use reduced from 1.48 (SD 0.99) to 0.60 (SD 0.86) [p < 0.001], insulin usage reduced from 27.9 to 10.5% (p < 0.001), and T2DM control improved from 27.9 to 82% (p < 0.001). The patients had a median excess BMI loss of 69.4% (IQR 34%) and 53.2% (IQR 36.0%) for RYGB and SG respectively (p = 0.016). At one year following surgery, there is no difference between LRYGB and LSG in terms of diabetic remission. LSG is not inferior to LRYGB in terms of early diabetic outcomes. Milder T2DM shows a better response. LSG is a simpler procedure with a lower risk profile and should be considered as an early treatment option for obese patients with T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Derivação Gástrica , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/cirurgia , População do Sudeste Asiático , Gastrectomia , Obesidade/complicações , Obesidade/cirurgia
12.
Int J Gen Med ; 17: 245-251, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38283077

RESUMO

Introduction: The pandemic of SARS-CoV-2 brings great challenge and threats to humans worldwide. Multiple variants of SARS-CoV-2 tend to be epidemic, among which Omicron is highly infectious within China. The aim of this study was to analyze the clinical characteristics of children infected with SARS-CoV-2 variant B.1.1.529 (Omicron) in the Shanghai, China. Methods: We included 9378 pediatric patients diagnosed with Omicron and treated in the Shanghai International Convention and Exhibition Center between April 1, 2022 and May 31, 2022. We recorded and summarized the clinical characteristics, infectious conditions and biological features of the children infected with Omicron. Results: A total of 9355 paediatric patients were treated in isolation since Makeshift became available, including 5564 males (59.48%) and 3791 females (40.52%). More than half (55.56%) of the affected children were identified at premises screening. The number of symptomatic or asymptomatic patients was 4530 (48.42%) and 4825 (51.58%), respectively. Initial signs or symptoms in asymptomatic patients included fatigue (3582, 38.29%), cough (560, 5.99%), fever (242, 2.59%) and other (146, 1.56%). Age and number of vaccinations in paediatric patients were negatively associated with the number of days from positive to negative nucleic acid test results. Conclusion: Age and number of vaccinations were key factors influencing the conversion of nucleic acid test results in paediatric patients. Early childhood vaccination is encouraged to establish a complete immune barrier.

14.
Adv Mater ; 36(5): e2307645, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37989269

RESUMO

Sodium metal has become one of the most promising anodes for next-generation cheap and high-energy-density metal batteries; however, challenges caused by the uncontrollable sodium dendrite growth and fragile solid electrolyte interphase (SEI) restrict their large-scale practical applications in low-cost and wide-voltage-window carbonate electrolytes. Herein, a novel multifunctional separator with lightweight and high thinness is proposed, assembled by the cobalt-based metal-organic framework nanowires (Co-NWS), to replace the widely applied thick and heavy glass fiber separator. Benefitting from its abundant sodiophilic functional groups and densely stacked nanowires, Co-NWS not only exhibits outstanding electrolyte wettability and effectively induces uniform Na+ ion flux as a strong ion redistributor but also favors constructing the robust N,F-rich SEI layer. Satisfactorily, with 10 µL carbonate electrolyte, a Na|Co-NWS|Cu half-cell delivers stable cycling (over 260 cycles) with a high average Coulombic efficiency of 98%, and the symmetric cell shows a long cycle life of more than 500 h. Remarkably, the full cell shows a long-term life span (over 1500 cycles with 92% capacity retention) at high current density in the carbonate electrolyte. This work opens up a strategy for developing dendrite-free, low-cost, and long-life-span sodium metal batteries in carbonate-based electrolytes.

15.
Int J Parasitol ; 54(2): 99-107, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37774810

RESUMO

The successful completion of gamete fertilization is essential for malaria parasite transmission, and this process can be targeted by intervention strategies. In this study, we identified a conserved gene (PBANKA_0813300) in the rodent malaria parasite Plasmodium berghei, which encodes a protein of 54 kDa (designated as Pbs54). Localization studies indicated that Pbs54 is associated with the plasma membranes of gametes and ookinetes. Functional studies by gene disruption showed that the Δpbs54 parasites had no defect in asexual proliferation, gametocyte development, or gametogenesis. However, the interactions between male and female gametes were significantly decreased compared with wild-type parasites. The Δpbs54 lines did not show a further reduction in zygote and ookinete numbers during in vitro culture, indicating that the defects were probably restricted to gamete fertilization. Consistent with this finding, mosquitoes fed on Δpbs54-infected mice showed a 30.1% reduction in infection prevalence and a 74.7% reduction in oocyst intensity. Cross-fertilization assay indicated that both male and female gametes were impaired in the Δpbs54 parasites. To evaluate its transmission-blocking potential, we obtained polyclonal antibodies from mice immunized with the recombinant Pbs54 (rPbs54) protein. In vitro assays showed that anti-rPbs54 sera inhibited ookinete formation by 42.7%. Our experiments identified Pbs54 as a fertility factor required for mosquito transmission and a novel candidate for a malaria transmission-blocking vaccine.


Assuntos
Culicidae , Vacinas Antimaláricas , Malária , Animais , Feminino , Masculino , Camundongos , Anticorpos Antiprotozoários , Fertilização , Células Germinativas , Malária/prevenção & controle , Proteínas de Membrana/genética , Plasmodium berghei/genética , Plasmodium berghei/metabolismo , Proteínas de Protozoários/metabolismo , Proteínas Recombinantes
16.
Nat Commun ; 14(1): 8068, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38057299

RESUMO

Gas hydrates provide alternative solutions for gas storage & transportation and gas separation. However, slow formation rate of clathrate hydrate has hindered their commercial development. Here we report a form of porous ice containing an unfrozen solution layer of sodium dodecyl sulfate, here named active ice, which can significantly accelerate gas hydrate formation while generating little heat. It can be readily produced via forming gas hydrates with water containing very low dosage (0.06 wt% or 600 ppm) of surfactant like sodium dodecyl sulfate and dissociating it below the ice point, or by simply mixing ice powder or natural snow with the surfactant. We prove that the active ice can rapidly store gas with high storage capacity up to 185 Vg Vw-1 with heat release of ~18 kJ mol-1 CH4 and the active ice can be easily regenerated by depressurization below the ice point. The active ice undergoes cyclic ice-hydrate-ice phase changes during gas uptake/release, thus removing most critical drawbacks of hydrate-based technologies. Our work provides a green and economic approach to gas storage and gas separation and paves the way to industrial application of hydrate-based technologies.

17.
Front Nutr ; 10: 1282376, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37915619

RESUMO

Rational: Maternal overweight/obesity and gestational diabetes mellitus (GDM) are associated with an increased risk of their offspring developing overweight/obesity or type 2 diabetes later in life. However, the impacts of maternal overweight/obesity and dysglycemia on human milk (HM) macronutrient composition are not well understood. Objective: Through a double-blind randomised controlled trial, we investigated the effects of maternal supplementation from preconception throughout pregnancy until birth on HM macronutrient concentrations, in association with maternal and infant factors including maternal pre-pregnancy body mass index (BMI) and GDM status. In addition, we aimed to characterise longitudinal changes in HM macronutrients. Methods: The control supplement contained calcium, iodine, iron, ß-carotene, and folic acid. The intervention supplement additionally contained zinc, vitamins B2, B6, B12, and D3, probiotics, and myo-inositol. HM samples were collected across seven time points from 1 week to 12 months from Singapore and/or New Zealand. HM macronutrient concentrations were measured using a MIRIS Human Milk Analyser. Potential differences in HM macronutrient concentrations were assessed using linear mixed models with a repeated measures design. Results: Overall, HM macronutrient concentrations were similar between control and intervention groups. Among the control group, overweight/obesity and GDM were associated with higher HM fat and energy concentrations over the first 3 months. Such associations were not observed among the intervention group. Of note, mothers with GDM in the intervention group had lower HM fat by 10% (p = 0.049) and energy by 6% (p = 0.029) than mothers with GDM in the control group. Longitudinal changes in HM macronutrient concentrations over 12 months of lactation in New Zealand showed that HM fat and energy decreased in the first 6 months then increased until 12 months. HM lactose gradually decreased from 1 week to 12 months while crude protein decreased from 1 week to 6 months then remained relatively constant until 12 months of lactation. Conclusion: Maternal overweight/obesity or GDM were associated with increased HM fat and energy levels. We speculate the intervention taken during preconception and pregnancy altered the impact of maternal BMI or GDM status on HM macronutrient composition. Further studies are required to identify the mechanisms underlying altered HM macronutrient concentration in the intervention group and to determine any long-term effects on offspring health. Clinical trial registration: ClinicalTrials.gov, NCT02509988, Universal Trial Number U1111-1171-8056. Registered on 16 July 2015. This is an academic-led study by the EpiGen Global Research Consortium.

18.
Clin Chem ; 69(12): 1420-1428, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37932245

RESUMO

BACKGROUND: Glycated albumin (GA) has recently been proposed as a screening marker for diabetes among non-pregnant individuals. However, data on GA during pregnancy are sparse and lacking among women of diverse race/ethnicity. We investigated longitudinal concentrations of GA among multiracial pregnant women in the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singletons. METHODS: We quantified GA and cardiometabolic biomarkers using longitudinal plasma samples collected at 10 to 14, 15 to 26 (fasting), 23 to 31, and 33 to 39 gestational weeks from 214 pregnant women without gestational diabetes. We examined the distribution of GA across pregnancy and its association with participants' characteristics including race/ethnicity, pre-pregnancy body mass index (ppBMI), and selected cardiometabolic biomarkers. GA trajectories were estimated using a latent class approach. RESULTS: Medians (interquartile range) of GA concentrations were 12.1% (10.6%-13.4%), 12.5% (10.7%-13.8%), 12.4% (10.9%-13.5%), and 11.5% (10.4%-12.5%) at 10 to 14, 15 to 26, 23 to 31, and 33 to 39 weeks, respectively. There were no significant differences in the pattern among different race/ethnic groups (P > 0.53). A minority of women exhibited a GA trajectory characterized by a high concentration of GA at 15 to 26 weeks. GA concentrations were inversely related to ppBMI and plasma low-density lipoprotein and triglyceride concentrations, but were not significantly related to hemoglobin A1c, fasting insulin, or glucose over pregnancy. CONCLUSIONS: In this study of individuals who were normoglycemic before pregnancy, plasma GA concentrations stayed relatively constant over pregnancy, decreasing only in late pregnancy. GA concentrations were inversely related to ppBMI and suboptimal lipid profiles, but did not appear to be a sensitive marker for glucose metabolism in pregnancy.


Assuntos
Doenças Cardiovasculares , Diabetes Gestacional , Criança , Gravidez , Feminino , Humanos , Estudos Longitudinais , Diabetes Gestacional/diagnóstico , Albumina Sérica/metabolismo , Biomarcadores , Glicemia/metabolismo
19.
Int J Mol Sci ; 24(20)2023 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-37895128

RESUMO

Anticancer peptides (ACPs) have been proven to possess potent anticancer activities. Although computational methods have emerged for rapid ACPs identification, their accuracy still needs improvement. In this study, we propose a model called ACP-BC, a three-channel end-to-end model that utilizes various combinations of data augmentation techniques. In the first channel, features are extracted from the raw sequence using a bidirectional long short-term memory network. In the second channel, the entire sequence is converted into a chemical molecular formula, which is further simplified using Simplified Molecular Input Line Entry System notation to obtain deep abstract features through a bidirectional encoder representation transformer (BERT). In the third channel, we manually selected four effective features according to dipeptide composition, binary profile feature, k-mer sparse matrix, and pseudo amino acid composition. Notably, the application of chemical BERT in predicting ACPs is novel and successfully integrated into our model. To validate the performance of our model, we selected two benchmark datasets, ACPs740 and ACPs240. ACP-BC achieved prediction accuracy with 87% and 90% on these two datasets, respectively, representing improvements of 1.3% and 7% compared to existing state-of-the-art methods on these datasets. Therefore, systematic comparative experiments have shown that the ACP-BC can effectively identify anticancer peptides.


Assuntos
Memória de Curto Prazo , Peptídeos , Peptídeos/farmacologia , Peptídeos/química , Dipeptídeos , Aminoácidos
20.
Nanoscale ; 15(42): 17105-17112, 2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37850316

RESUMO

Virus infections remain one of the principal causes of morbidity and mortality worldwide. The current gold standard approach for diagnosing pathogens requires access to reverse transcription-polymerase chain reaction (RT-PCR) technology. However, separation and enrichment of the targets from complex and diluted samples remains a major challenge. In this work, we proposed a micromotor-based sample preparation concept for the efficient separation and concentration of target viral particles before PCR. The micromotors are functionalized with antibodies with a 3D polymer linker and are capable of self-propulsion by the catalytic generation of oxygen bubbles for selective and positive virus enrichment. This strategy significantly improves the enrichment efficiency and recovery rate of virus (up to 80% at 104 tu mL-1 in a 1 mL volume within just 6 min) without external mixing equipment. The method allows the Ct value in regular PCR tests to appear 6-7 cycles earlier and a detection limit of 1 tu mL-1 for the target virus from swap samples. A point-of-need test kit is designed based on the micromotors which can be readily applied to pretreat a large volume of samples.


Assuntos
Oxigênio , Polímeros , Catálise , Vírion
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