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Tremendous attention has been paid to the water-associated side reactions and zinc (Zn) dendrite growth on the electrode-electrolyte interface. However, the Zn pulverization that can cause continuous depletion of active Zn metal and exacerbate hydrogen evolution is severely neglected. Here, we disclose that the excessive Zn feeding that causes incomplete crystallization is responsible for Zn pulverization formation through analyzing the thermodynamic and kinetics process of Zn deposition. On the basis, we introduce 1-ethyl-3-methylimidazolium cations (EMIm+) into the electrolyte to form a Galton-board-like three-dimensional inert-cation (3DIC) region. Modeling test shows that the 3DIC EMIm+ can induce the Zn2+ flux to follow in a Gauss distribution, thus acting as elastic sites to buffer the perpendicular diffusion of Zn2+ and direct the lateral diffusion, thus effectively avoiding the local Zn2+ accumulation and irreversible crystal formation. Consequently, anti-pulverized Zn metal deposition behavior is achieved with an average Coulombic efficiency of 99.6% at 5 mA cm-2 over 2,000 cycles and superb stability in symmetric cell over 1,200 h at -30 °C. Furthermore, the Zn||KVOH pouch cell can stably cycle over 1,200 cycles at 2 A g-1 and maintain a capacity of up to 12 mAh.
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The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe and fatal acute respiratory disease in humans. High fatality rates and continued infectiousness remain a pressing concern for global health preparedness. Antibodies targeted at the receptor-binding domain (RBD) are major countermeasures against human viral infection. Here, we report four potent nanobodies against MERS-CoV, which are isolated from alpaca, and especially the potency of Nb14 is highest in the pseudotyped virus assay. Structural studies show that Nb14 framework regions (FRs) are mainly involved in interactions targeting a novel epitope, which is entirely distinct from all previously reported antibodies, and disrupt the protein-carbohydrate interaction between residue W535 of RBD and hDPP4 N229-linked carbohydrate moiety (hDPP4-N229-glycan). Different from Nb14, Nb9 targets the cryptic face of RBD, which is distinctive from the hDPP4 binding site and the Nb14 epitope, and it induces the ß5-ß6 loop to inflect towards a shallow groove of the RBD and dampens the accommodation of a short helix of hDPP4. The particularly striking epitopes endow the two Nbs administrate synergistically in the pseudotyped MERS-CoV assays. These results not only character unprecedented epitopes for antibody recognition but also provide promising agents for prophylaxis and therapy of MERS-CoV infection.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Infecciones por Coronavirus , Epítopos , Coronavirus del Síndrome Respiratorio de Oriente Medio , Anticuerpos de Dominio Único , Coronavirus del Síndrome Respiratorio de Oriente Medio/inmunología , Anticuerpos de Dominio Único/inmunología , Anticuerpos de Dominio Único/química , Humanos , Epítopos/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Animales , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Camélidos del Nuevo Mundo/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/química , Ratones , Receptores Virales/metabolismo , Receptores Virales/inmunologíaRESUMEN
Xenobiotic nucleic acids (XNAs) are artificial genetic polymers with altered structural moieties and useful features, such as enhanced biological and chemical stability. Enzymatic synthesis and efficient labelling of XNAs are crucial for their broader application. Terminal deoxynucleotidyl transferases (TdTs) have been exploited for the de novo synthesis and labelling of DNA and demonstrated the capability of recognizing various substrates. However, the activities of TdTs for the synthesis and labelling of commonly used XNAs with 2' modifications have not been systematically explored. In this work, we explored and demonstrated the varied activities of three TdTs (bovine TdT, MTdT-evo and murine TdT) for the template-independent incorporation of 2'-methoxy NTPs, 2'-fluoro NTPs and 2'-fluoroarabino NTPs into the 3' ends of single- and double-stranded DNAs and the extension of 2'-modified XNAs with (d)NTPs containing a natural or unnatural nucleobase. Taking advantages of these activities, we established a strategy for protecting single-stranded DNAs from exonuclease I degradation by TdT-synthesized 2'-modified XNA tails and methods for 3'-end labelling of 2'-modified XNAs by TdT-mediated synthesis of G-quadruplex-containing tails or incorporation of nucleotides with a functionalized nucleobase. A DNA-2'-fluoroarabino nucleic acid (FANA) chimeric hydrogel was also successfully constructed based on the extraordinary activity of MTdT-evo for template-independent FANA synthesis.
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Potassium-ion batteries (PIBs) have attracted ever-increasing interest due to the abundant potassium resources and low cost, which are considered a sustainable energy storage technology. However, the graphite anodes employed in PIBs suffer from low capacity and sluggish reaction kinetics caused by the large radius of potassium ions. Herein, we report nitrogen-doped, defect-rich hollow carbon nanospheres with contact curved interfaces (CCIs) on carbon nanotubes (CNTs), namely CCI-CNS/CNT, to boost both electron transfer and potassium-ion adsorption. Density functional theory calculations validate that engineering CCIs significantly augments the electronic state near the Fermi level, thus promoting electron transfer. In addition, the CCIs exhibit a pronounced affinity for potassium ions, promoting their adsorption and subsequently benefiting potassium storage. As a result, the rationally designed CCI-CNS/CNT anode shows remarkable cyclic stability and rate capability. This work provides a strategy for enhancing the potassium storage performance of carbonaceous materials through CCI engineering, which can be further extended to other battery systems.
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Small RNAs are widely involved in plant immune responses. However, the role of long small RNAs (25 to 40 nt) in monocot plant disease resistance is largely unknown. Here, we identified a long small RNA (lsiR76113) from rice (Oryza sativa) that is downregulated by Magnaporthe oryzae infection and targets a gene encoding CYCLIC NUCLEOTIDE-GATED CHANNEL 5 (CNGC5). The cngc5 mutant lines were more susceptible to M. oryzae than the wild type, while knocking down lsiR76113 in transgenic rice plants promoted pathogen resistance. A protoplast transient expression assay showed that OsCNGC5 promotes Ca2+ influx. These results demonstrate that OsCNGC5 enhances rice resistance to rice blast by increasing the cytosolic Ca2+ concentration. Importantly, exogenous Ca2+ application enhanced rice M. oryzae resistance by affecting reactive oxygen species (ROS) production. Moreover, cngc5 mutants attenuated the PAMP-triggered immunity response, including chitin-induced and flg22-induced ROS bursts and protein phosphorylation in the mitogen-activated protein kinase cascade, indicating that OsCNGC5 is essential for PAMP-induced calcium signaling in rice. Taken together, these results suggest that lsiR76113-mediated regulation of Ca2+ influx is important for PTI responses and disease resistance in rice.
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Calcio , Resistencia a la Enfermedad , Resistencia a la Enfermedad/genética , Especies Reactivas de Oxígeno , Canales Catiónicos Regulados por Nucleótidos Cíclicos , Plantas Modificadas Genéticamente , ARN , Nucleótidos CíclicosRESUMEN
AIMS/HYPOTHESIS: Continuous glucose monitoring (CGM) provides comprehensive information on the exposure to dysglycaemia. This study aimed to investigate the threshold of hyperglycaemia related to mortality risk in critically ill patients using CGM technology. METHODS: A total of 293 adult critically ill patients admitted to intensive care units of five medical centres were prospectively included between May 2020 and November 2021. Participants wore intermittently scanned CGM for a median of 12.0 days. The relationships between different predefined time above ranges (TARs), with the thresholds of hyperglycaemia ranging from 7.8 to 13.9 mmol/l (140-250 mg/dl), and in-hospital mortality risk were assessed by multivariate Cox proportional regression analysis. Time in ranges (TIRs) of 3.9 mmol/l (70 mg/dl) to the predefined hyperglycaemic thresholds were also assessed. RESULTS: Overall, 66 (22.5%) in-hospital deaths were identified. Only TARs with a threshold of 10.5 mmol/l (190 mg/dl) or above were significantly associated with the risk of in-hospital mortality, after adjustment for covariates. Furthermore, as the thresholds for TAR increased from 10.5 mmol/l to 13.9 mmol/l (190 mg/dl to 250 mg/dl), the hazards of in-hospital mortality increased incrementally with every 10% increase in TARs. Similar results were observed concerning the associations between TIRs with various upper thresholds and in-hospital mortality risk. For per absolute 10% decrease in TIR 3.9-10.5 mmol/l (70-190 mg/dl), the risk of in-hospital mortality was increased by 12.1% (HR 1.121 [95% CI 1.003, 1.253]). CONCLUSIONS/INTERPRETATION: A glucose level exceeding 10.5 mmol/l (190 mg/dl) was significantly associated with higher risk of in-hospital mortality in critically ill patients.
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Glucemia , Enfermedad Crítica , Mortalidad Hospitalaria , Hiperglucemia , Humanos , Enfermedad Crítica/mortalidad , Hiperglucemia/mortalidad , Hiperglucemia/sangre , Masculino , Estudios Prospectivos , Femenino , Glucemia/análisis , Glucemia/metabolismo , Persona de Mediana Edad , Anciano , Unidades de Cuidados Intensivos , Monitoreo Fisiológico/métodos , Monitoreo Continuo de GlucosaRESUMEN
In recent years, the CRISPR/Cas12a-based sensing strategy has shown significant potential for specific target detection due to its rapid and sensitive characteristics. However, the "always active" biosensors are often insufficient to manipulate nucleic acid sensing with high spatiotemporal control. It remains crucial to develop nucleic acid sensing devices that can be activated at the desired time and space by a remotely applied stimulus. Here, we integrated photoactivation with the CRISPR/Cas12a system for DNA and RNA detection, aiming to provide high spatiotemporal control for nucleic acid sensing. By rationally designing the target recognition sequence, this photoactivation CRISPR/Cas12a system could recognize HPV16 and survivin, respectively. We combined the lateral flow assay strip test with the CRISPR/Cas12a system to realize the visualization of nucleic acid cleavage signals, displaying potential instant test application capabilities. Additionally, we also successfully realized the temporary control of its fluorescent sensing activity for survivin by photoactivation in vivo, allowing rapid detection of target nucleic acids and avoiding the risk of contamination from premature leaks during storage. Our strategy suggests that the CRISPR/Cas12a platform can be triggered by photoactivation to sense various targets, expanding the technical toolbox for precise biological and medical analysis. This study represents a significant advancement in nucleic acid sensing and has potential applications in disease diagnosis and treatment.
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Técnicas Biosensibles , Ácidos Nucleicos , Sistemas CRISPR-Cas/genética , Survivin/genética , Biomarcadores , Pruebas en el Punto de AtenciónRESUMEN
Energy metabolism has always been a hot topic in cancer progression and targeted therapy, and exploring the role of genes in energy metabolic pathways in cancer cells has become key to address this issue. Eukaryotic translation initiation factor 2α kinase 2 (EIF2AK2) plays regulatory roles in cancer and disorders of energy metabolism. Indeed, the role of EIF2AK2 in energy metabolism has been underestimated. The aim of this study is to reveal the expression specificity of EIF2AK2 in gastric cancer (GC) progression and metastasis, and to demonstrate the role of EIF2AK2 in energy metabolism, cytoskeleton, proliferation, death and metastasis pathways in GC cells. Mechanistically, EIF2AK2 overexpression promoted cytoskeleton remodeling and ATP production, mediated cell proliferation and metastasis, upregulated OAS1 expression, decreases p-AMPK expression and inhibited apoptosis in GC cells. Conversely, knockdown of EIF2AK2 resulted in the opposite effect. However, overexpression of OAS1 mediated the upregulation of mitochondrial membrane potential and promoted ATP production and NAD+/NADH ratio, but knockdown of OAS1 inhibited the above effects. In addition, knockdown of OAS1 had no effect on EIF2AK2 expression, but inhibited AMPK and upregulated p-AMPK expression. In conclusion, our study identified EIF2AK2 and OAS1 as previously undescribed regulators of energy metabolism in GC cells. We hypothesized that EIF2AK2-OAS1 axis may regulate energy metabolism and inhibit cellular malignant behavior in cancer cells by affecting ATP production to induce AMPK phosphorylation, suggesting EIF2AK2 as a potential therapeutic target for cancer cell progression.
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Proteínas Quinasas Activadas por AMP , Adenosina Trifosfato , Neoplasias Gástricas , eIF-2 Quinasa , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , Humanos , Adenosina Trifosfato/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , eIF-2 Quinasa/metabolismo , Fosforilación , Línea Celular Tumoral , Técnicas de Silenciamiento del GenRESUMEN
In recent years, the visible light positioning field has experienced remarkable advancements. However, smartphones find it difficult to identify light-emitting diode (LED) and extract each LED's light signal intensity due to the low-frequency and uneven sampling of built-in ambient light sensors (ALS, which is a photodiode that measures ambient light in lux units). Thus, traditional visible light positioning systems cannot be directly applied to smartphones. In this Letter, we propose a single-light visible light positioning system using a non-modulated LED as an emitter, the built-in ALS as the receiver, and the inertial measurement unit of the smartphone to assist in measuring the smartphone's attitude. It only requires the user to turn the smartphone by a few angles in a stationary position to estimate its current three-dimensional (3D) spatial position. This method does not require modification of the existing lighting system and consumes less power than the camera-based visible light positioning (VLP) systems. We have built an experimental site measuring 5 m × 5 m × 2.2 m to evaluate the performance of the positioning system, and the preliminary results show that the proposed system achieves sub-meter-level positioning accuracy.
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Förster resonance energy transfer (FRET) has been widely applied in fluorescence imaging, sensing and so on, while developing useful strategy of boosting FRET efficiency becomes a key issue that limits the application. Except optimizing spectral properties, promoting orientation factor (κ2) has been well discussed but rarely utilized for boosting FRET. Herein, we constructed binary nano-assembling of two thermally activated delayed fluorescence (TADF) emitters (2CzPN and DMAC-DPS) with J-type aggregate of cyanine dye (C8S4) as doping films by taking advantage of their electrostatic interactions. Time-resolved spectroscopic measurements indicated that 2CzPN/Cy-J films exhibit an order of magnitude higher kFRET than DMAC-DPS/Cy-J films. Further quantitative analysing on kFRET and kDET indicated higher orientation factor (κ2) in 2CzPN/Cy-J films play a key role for achieving fast kFRET, which was subsequently confirmed by anisotropic measurements. Corresponding DFT/TDDFT calculation revealed strong "two-point" electrostatic anchoring in 2CzPN/Cy-J films that is responsible for highly orientated transitions. We provide a new strategy for boosting FRET in nano-assemblies, which might be inspired for designing FRET-based devices of sensing, imaging and information encryption.
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Engineered bacteria-based cancer therapy has increasingly been considered to be a promising therapeutic strategy due to the development of synthetic biology. Wherein, engineering bacteria-mediated photodynamic therapy (PDT)-immunotherapy shows greater advantages and potential in treatment efficiency than monotherapy. However, the unsustainable regeneration of photosensitizers (PSs) and weak immune responses limit the therapeutic efficiency. Herein, we developed an engineered bacteria-based delivery system for sequential delivery of PSs and checkpoint inhibitors in cancer PDT-immunotherapy. The biosynthetic pathway of 5-aminolevulinic acid (5-ALA) was introduced into Escherichia coli, yielding a supernatant concentration of 172.19 mg/L after 10 h of growth. And another strain was endowed with the light-controllable releasement of anti-programmed cell death-ligand 1 nanobodies (anti-PD-L1). This system exhibited a collaborative effect, where PDT initiated tumor cell death and the released tumor cell fragments stimulated immunity, followed by the elimination of residual tumor cells. The tumor inhibition rate reached 74.97%, and the portion of activated T cells and inflammatory cytokines were reinforced. The results demonstrated that the engineered bacteria-based collaborative system could sequentially deliver therapeutic substance and checkpoint inhibitors, and achieve good therapeutic therapy. This paper will provide a new perspective for the cancer PDT-immunotherapy.
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BACKGROUND: Glucosamine is a dietary supplement commonly used to support joint health. However, there has been interest in exploring other effects of glucosamine on health outcomes due to its ant-inflammation effect. OBJECTIVE: This study compared the risks of major adverse liver outcomes (MALOs) between regular users and non-users of glucosamine among patients with type 2 diabetes and metabolic dysfunction associated steatotic liver disease (MASLD) using the data from a large prospective cohort study. METHODS: Demographic, anthropometric, laboratory and medication prescription information among 18 753 patients with type 2 diabetes and MASLD was obtained from the UK Biobank. MASLD was identified based on hepatic steatosis defined by fatty liver index ≥60 plus the presence of any clues of metabolic dysregulation and cardio-metabolic risk factors, excluding patients with moderate to severe alcohol consumption. RESULTS: During a mean follow-up of 11.4 years, 826 incident MALOs events were recorded. Patients not regularly using glucosamine compared with patients using glucosamine showed a significantly higher risk of the composite MALOs (HR 1.36, 95% confidence interval [CI] 1.09-1.69) as well as most individual MALOs except for ascites. The multivariable-adjusted HRs of MALOs within 3, 5 and 10 years among non-users of glucosamine compared with regular users were 1.79 (95% CI .69-2.03), 1.88 (95% CI 1.21-2.54) and 1.32 (95% CI 1.05-1.72), respectively. Further subgroup analyses in participants with different baseline characteristics and sensitivity analyses excluding participants who regularly took any other supplements and participants who used self-reports to diagnose diabetes confirmed the findings. CONCLUSIONS: The present study indicated that habitual use of glucosamine was associated with a low risk of individual and composite MALOs among patients with type 2 diabetes and MASLD.
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AIM: The wealth of data generated by continuous glucose monitoring (CGM) provides new opportunities for revealing heterogeneities in patients with type 2 diabetes mellitus (T2DM). We aimed to develop a method using CGM data to discover T2DM subtypes and investigate their relationship with clinical phenotypes and microvascular complications. METHODS: The data from 3119 patients with T2DM who wore blinded CGM at an academic medical centre was collected, and a glucose symbolic pattern (GSP) metric was created that combined knowledge-based temporal abstraction with numerical vectorization. The k-means clustering was applied to GSP to obtain subgroups of patients with T2DM. Clinical characteristics and the presence of diabetic retinopathy and albuminuria were compared among the subgroups. The findings were validated in an independent population comprising 773 patients with T2DM. RESULTS: By using GSP, four subgroups were identified with distinct features in CGM profiles and parameters. Moreover, the clustered subgroups differed significantly in clinical phenotypes, including indices of pancreatic ß-cell function and insulin resistance (all p < .001). After adjusting for confounders, group C (the most insulin resistant) had a significantly higher risk of albuminuria (odds ratio = 1.24, 95% confidence interval: 1.03-1.39) relative to group D, which had the best glucose control. These findings were confirmed in the validation set. CONCLUSION: Subtyping patients with T2DM using CGM data may help identify high-risk patients for microvascular complications and provide insights into the underlying pathophysiology. This method may help refine clinically meaningful stratification of patients with T2DM and inform personalized diabetes care.
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Albuminuria , Automonitorización de la Glucosa Sanguínea , Glucemia , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Masculino , Persona de Mediana Edad , Glucemia/metabolismo , Glucemia/análisis , Albuminuria/sangre , Anciano , Retinopatía Diabética/sangre , Retinopatía Diabética/etiología , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/epidemiología , Resistencia a la Insulina , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/diagnóstico , Adulto , Monitoreo Continuo de GlucosaRESUMEN
AIMS: To characterize the comparative contributions of different glycaemic indicators to cognitive dysfunction, and further investigate the associations between the most significant indicator and cognitive function, along with related cerebral alterations. MATERIALS AND METHODS: We performed a cross-sectional study in 449 subjects with type 2 diabetes who completed continuous glucose monitoring and cognitive assessments. Of these, 139 underwent functional magnetic resonance imaging to evaluate cerebral structure and olfactory neural circuit alterations. Relative weight and Sobol's sensitivity analyses were employed to characterize the comparative contributions of different glycaemic indicators to cognitive dysfunction. RESULTS: Complexity of glucose time series index (CGI) was found to have a more pronounced association with mild cognitive impairment (MCI) compared to glycated haemoglobin, time in range, and standard deviation. The proportion and multivariable-adjusted odds ratios (ORs) for MCI increased with descending CGI tertile (Tertile 1: reference group [≥4.0]; Tertile 2 [3.6-4.0] OR 1.23, 95% confidence interval [CI] 0.68-2.24; Tertile 3 [<3.6] OR 2.27, 95% CI 1.29-4.00). Decreased CGI was associated with cognitive decline in executive function and attention. Furthermore, individuals with decreased CGI displayed reduced olfactory activation in the left orbitofrontal cortex (OFC) and disrupted functional connectivity between the left OFC and right posterior cingulate gyrus. Mediation analysis demonstrated that the left OFC activation partially mediated the associations between CGI and executive function. CONCLUSION: Decreased glucose complexity closely relates to cognitive dysfunction and olfactory brain activation abnormalities in diabetes.
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Disfunción Cognitiva , Diabetes Mellitus Tipo 2 , Adulto , Humanos , Glucosa , Factores de Tiempo , Estudios Transversales , Automonitorización de la Glucosa Sanguínea , Glucemia , Cognición , Disfunción Cognitiva/etiología , Imagen por Resonancia Magnética/métodos , Encéfalo/patologíaRESUMEN
AIM: We investigated the relationship between the complexity of the glucose time series index (CGI) during pregnancy and adverse pregnancy outcomes in women with gestational diabetes mellitus (GDM). MATERIALS AND METHODS: In this retrospective cohort study, 388 singleton pregnant women with GDM underwent continuous glucose monitoring (CGM) at a median of 26.86 gestational weeks. CGI was calculated using refined composite multiscale entropy based on CGM data. The participants were categorized into tertiles according to their baseline CGI (CGI <2.32, 2.32-3.10, ≥3.10). Logistic regression was used to assess the association between CGI and composite adverse outcomes or large for gestational age (LGA). The discrimination performance of CGI was estimated using receiver operating characteristic analysis. RESULTS: Of the 388 participants, 71 (18.3%) had LGA infants and 63 (16.2%) had composite adverse outcomes. After adjustments were made for confounders, compared with those with a high CGI (CGI ≥3.10), participants with a low CGI (CGI <2.32) had a higher risk of composite adverse outcomes (odds ratio: 12.10, 95% confidence interval: 4.41-33.18) and LGA (odds ratio: 12.68, 95% confidence interval: 4.04-39.75). According to the receiver operating characteristic analysis, CGI was significantly better than glycated haemoglobin and conventional CGM indicators for the prediction of adverse pregnancy outcomes (all p < .05). CONCLUSION: A lower CGI during pregnancy was associated with composite adverse outcomes and LGA. CGI, a novel glucose homeostasis predictor, seems to be superior to conventional glucose indicators for the prediction of adverse pregnancy outcomes in women with GDM.
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Automonitorización de la Glucosa Sanguínea , Glucemia , Diabetes Gestacional , Resultado del Embarazo , Humanos , Embarazo , Femenino , Diabetes Gestacional/sangre , Adulto , Estudios Retrospectivos , Glucemia/análisis , Glucemia/metabolismo , Resultado del Embarazo/epidemiología , Macrosomía Fetal/epidemiología , Macrosomía Fetal/etiología , Hemoglobina Glucada/análisis , Hemoglobina Glucada/metabolismo , Recién NacidoRESUMEN
OBJECTIVE: We sought to investigate the impact of individualized exercise guidance during pregnancy on the incidence of macrosomia and the mediating effect of gestational weight gain (GWG). DESIGN: A prospective randomized clinical trial. SETTING: A Hospital in Xingtai District, Hebei Province. POPULATION: Older than 20 years of age, mid-pregnancy, and singleton pregnant women without contraindications to exercise during pregnancy. METHODS: A randomized clinical trial was conducted from December 2021 to September 2022 to compare the effects of standard prenatal care with individualized exercise guidance on the incidence of macrosomia. MAIN OUTCOME MEASURE: Incidence of macrosomia. RESULTS: In all, 312 singleton women were randomized into an intervention group (N = 162) or a control group (N = 150). Participants who received individualized exercise guidance had a significantly lower incidence of macrosomia (3.73% vs. 13.61%, P = 0.002) and infants large for gestational age (9.94% vs. 19.73%, P = 0.015). However, no differences were observed in the rate of preterm birth (1.86% vs. 3.40%, P = 0.397) or the average gestational age at birth (39.14 ± 1.51 vs. 38.69 ± 1.85, P = 0.258). Mediation analysis revealed that GWG mediated the effect of exercise on reducing the incidence of macrosomia. CONCLUSION: Individualized exercise guidance may be a preventive tool for macrosomia, and GWG mediates the effect of exercise on reducing the incidence of macrosomia. However, evidence does not show that exercise increases the rate of preterm birth or affects the average gestational age at birth. TRIAL REGISTRATION: The trial is registered at www.clinicaltrails.gov [registration number: NCT05760768; registration date: 08/03/2023 (retrospectively registered)].
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Ejercicio Físico , Macrosomía Fetal , Ganancia de Peso Gestacional , Atención Prenatal , Humanos , Femenino , Macrosomía Fetal/prevención & control , Embarazo , Adulto , Atención Prenatal/métodos , Estudios Prospectivos , Incidencia , China/epidemiología , Recién NacidoRESUMEN
PURPOSE: This study aimed to investigate alterations of outer retinal reflectivity on spectral-domain optical coherence tomography (OCT) in diabetic patients without clinically detectable retinopathy (NDR). METHODS: In this retrospective study, 64 NDR patients and 71 controls were included. Relative reflectivity (RR) of the ellipsoid zone (EZ), photoreceptor outer segment (OS) and inner segment (IS), and outer nuclear layer (ONL) at the foveola and at 500 µm, 1000 µm, and 2000 µm nasal (N), temporal (T), superior (S), and inferior (I) to the foveola was measured by cross-line OCT and ImageJ. Retinal vessel densities (VD) in fovea, parafovea, and perifovea areas were detected by OCT angiography (OCTA). RESULTS: EZ RR in most retinal locations was significantly lower in NDR eyes compared to controls (all P < 0.05), except the foveola. Compared with controls, NDR eyes also displayed lower RR at N2000, T2000, S1000, and I1000 of OS, at S500 and I500 of IS, and at I500 of ONL (all P < 0.05). Negative correlations could be observed between retinal RR and diabetes duration, HbA1c, and best-corrected visual acuity (BCVA) (r = - 0.303 to - 0.452). Compared to controls, EZ, OS, and IS RR of the NDR eyes showed lower correlation coefficients with whole image SCP and DCP VD of parafovea and perifovea regions. CONCLUSION: Outer retinal reflectivity, along with the coefficients between retinal reflectivity and VD, is reduced in NDR patients and is correlated with diabetes duration, HbA1c, and BCVA. The reduction of outer retinal reflectivity may be a potential biomarker of early retinal alterations in diabetic patients.
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Diabetes Mellitus , Retinopatía Diabética , Enfermedades de la Retina , Humanos , Estudios Retrospectivos , Hemoglobina Glucada , Angiografía con Fluoresceína/métodos , Tomografía de Coherencia Óptica/métodos , Retinopatía Diabética/diagnósticoRESUMEN
Film bulk acoustic-wave resonators (FBARs) are widely utilized in the field of radio frequency (RF) filters due to their excellent performance, such as high operation frequency and high quality. In this paper, we present the design, fabrication, and characterization of an FBAR filter for the 3.0 GHz-3.2 GHz S-band. Using a scandium-doped aluminum nitride (Sc0.2Al0.8N) film, the filter is designed through a combined acoustic-electromagnetic simulation method, and the FBAR and filter are fabricated using an eight-step lithographic process. The measured FBAR presents an effective electromechanical coupling coefficient (keff2) value up to 13.3%, and the measured filter demonstrates a -3 dB bandwidth of 115 MHz (from 3.013 GHz to 3.128 GHz), a low insertion loss of -2.4 dB, and good out-of-band rejection of -30 dB. The measured 1 dB compression point of the fabricated filter is 30.5 dBm, and the first series resonator burns out first as the input power increases. This work paves the way for research on high-power RF filters in mobile communication.
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Electrolytic manganese residue (EMR) is known for high concentrations of Mn2+, NH4+, and heavy metals. Failure to undergo benign treatment and landfill disposal would undeniably lead to negative impacts on the quality of the surrounding ecological environment. This study sought to mitigate the latent environmental risks associated with EMR using a cooperative solidification/stabilization (S/S) method involving coal fly ash (CFA). Leveraging leaching toxicity tests, the leaching behavior of pollutants in electrolytic manganese residue-based geopolymer materials (EMRGM) was determined. At the same time, mechanistic insights into S/S processes were explored utilizing characterization techniques such as XRF, XRD, FT-IR, SEM-EDS, and XPS. Those results confirmed significant reductions in the leaching toxicities of Mn2+ and NH4+ to 4.64 µg/L and 0.99 mg/L, respectively, with all other heavy metal ions falling within the permissible limits set by relevant standards. Further analysis shows that most of NH4+ volatilizes into the air as NH3, and a small part is fixed in the EMRGM in the form of struvite; in addition to being oxidized to MnOOH and MnO2, Mn2+ will also be adsorbed and wrapped by silicon-aluminum gel together with other heavy metal elements in the form of ions or precipitation. This research undeniably provides a solid theoretical foundation for the benign treatment and resourceful utilization of EMR and CFA, two prominent industrial solid wastes.
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Ceniza del Carbón , Manganeso , Ceniza del Carbón/química , Manganeso/química , Metales Pesados/químicaRESUMEN
Sepsis is a multiple organ dysfunction syndrome due to a dysregulated response to infection with unacceptably high mortality. Currently, no effective treatment exists for sepsis. IRG1/itaconate has been considered to play a protective role for various inflammatory diseases. In the present study, we explored the protective role and mechanisms of IRG1/itaconate on lipopolysaccharide (LPS)-induced multi-organ injury. The LPS-induced sepsis model was used. IRG1-/- and wild type mice were used to explore the protective role of IRG1/itaconate on multi-organ injury. GSDMD-/- mice were used to explore the effect of GSDMD-mediated pyroptosis on LPS-induced model. RAW264.7 cells and bone-marrow-derived macrophages (BMDMs) were used for in vitro studies. In vivo experiments, we found IRG1 deficiency aggravated LPS-induced multi-organ injury especially lung injury. 4-Octyl itaconate (4-OI), a derivative of itaconate, significantly ameliorated LPS-induced acute lung, liver, and kidney injury. Furthermore, IRG1/4-OI decreased serum interleukin-1ß (IL-1ß), IL-6, tumor necrosis factor-α (TNF-α) level, macrophage infiltration, and TUNEL-positive cells in lung and liver tissue. Western blot showed IRG1/itaconate decreased the expressions of p-ERK, p-P38, p-JNK, and p-P65 and increased the expression of Nrf2/HO-1 in lung tissue. Meanwhile, 4-OI inhibited the expression of GSDMD-N. In vitro experiments, 4-OI inhibited ROS production and promoted apoptosis under LPS stimulation in RAW264.7 cells. Furthermore, 4-OI inhibited nuclear factor-kappaB/mitogen-activated protein kinase pathways and GSDMD-medicated pyroptosis in BMDMs. Finally, we used GSDMD-/- mice to explore the effect of pyroptosis on LPS-induced multi-organ injury. The results showed that GSDMD deficiency significantly ameliorated lung injury. In conclusion, our data demonstrated that IRG1/itaconate protect against multi-organ injury via inhibiting inflammation response and GSDMD-indicated pyroptosis, which may be a promising agent for protecting against sepsis.