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1.
Inorg Chem ; 63(29): 13295-13303, 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-38982625

RESUMEN

Targeting selective CO2 photoreduction into CH4 remains a challenge due to the sluggish reaction kinetics and poor hydrogenation ability of the unstable intermediate. Here, the active Pt2+ sites were photodeposited on the SrTiO3 photocatalyst, which was well demonstrated to manipulate the CH4 product selectivity. The results showed that SrTiO3 mainly yielded the CO (6.98 µmol g-1) product with poor CH4 (0.17 µmol g-1). With the Pt2+ modification, 100% CH4 selectivity could be obtained with an optimized yield rate of 8.07 µmol g-1. The prominent enhancement resulted from the following roles: (1) the strong electronic interaction between the Pt2+ cocatalyst and SrTiO3 could prompt efficient separation of the photoelectron-hole pairs. (2) The Pt2+ sites were active to capture and activate inert CO2 into HCO3- and CO32- species and allowed fast *COOH formation with the lowered reaction barrier. (3) Compared with SrTiO3, the formed *CO species could be captured tightly on the Pt2+ cocatalyst surface for generating the *CH2 intermediate by the following electron-proton coupling reaction, thus leading to the CH4 product with 100% selectivity.

2.
Pak J Med Sci ; 40(6): 1174-1179, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38952528

RESUMEN

Objective: To explore the clinical effect of laser acupuncture combined with Schroth therapy on adolescent idiopathic scoliosis (AIS). Method: This was a retrospective study. Eighty AIS patients were admitted to The Second People's Hospital of Dalian from March 2021 to March 2022 and divided into control group and experimental group according to the treatment method, with 40 cases in each group. The control group received Schroth therapy, and the experimental group received Schroth therapy and laser acupuncture therapy (MLS® laser). All treatments are performed five times a week for four consecutive weeks we compared the clinical effects of the two groups before treatment, six months and 12 months after treatment, and compared the improvement of Cobb angle, axial trunk rotation (ATR), musculoskeletal stiffness(The PulStarG3 system), and gait evaluation (Micro-Electro-Mechanical System(MEMS) between the two groups of patients. Result: After four weeks of treatment, the spinal condition of both groups of patients improved. After treatment, the experimental group showed greater improvement in Cobb angle, ATR, spinal range of motion, gait parameters, and clinical efficacy compared to the control group (p<0.05). Conclusion: Laser acupuncture combined with Schroth therapy is safe and effective in the treatment of AIS, and is more effective in correcting scoliosis and related problems of AIS.

3.
Nanotechnology ; 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39084235

RESUMEN

Indium oxide (In2O3) is a promising channel material for thin-film transistors (TFTs). In this work, we develop an atomic layer deposition (ALD) process of using trimethylindium (TMIn) and ozone (O3) to deposit In2O3 films and fabricate ultrathin In2O3 TFTs. The In2O3 TFTs with 4 nm channel thickness show generally good switching characteristics with a high Ion/Ioff of 108, a high mobility (µFE) of 16.2 cm^2 V^(-1) s^(-1) and a positive threshold voltage (Vth) of 0.48 V. Although the 4 nm In2O3 TFTs also exhibit short channel effect, it can be improved by adding an ALD Ga2O3 capping layer to afford the bilayer In2O3/Ga2O3 channel structure. The afforded In2O3/Ga2O3 TFTs exhibit improved immunity to the short channel effect, with good TFT characteristics of Ion/Ioff of 107, µFE of 9.3 cm^2 V^(-1) s^(-1), and positive Vth of 2.23 V. Overall, the thermal budget of the entire process is only 400 °C, which is suitable for the display and CMOS back-end-of-line (BEOL)-compatible applications.

4.
J Phys Chem A ; 128(30): 6264-6273, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39034617

RESUMEN

Accurate branching ratios of the H-abstraction reactions from dimethylamine (DMA) by OH radicals are important in understanding the atmospheric fate of DMA. In this work, the reaction kinetics of the water-free, water-assisted, and self-assisted H-abstraction reactions between DMA and OH radicals are accurately determined using the multipath canonical variational theory with the small-curvature tunneling correction, to explore the catalytic effects of the reactant (DMA) and product (water). To choose a suitable method that well describes the current reaction systems, various combinations with seven DFT methods and six basis sets are first evaluated, and the M08-HX/ma-TZVP method is identified as the most appropriate, with a mean unsigned deviation of 0.9 kcal mol-1 against the gold-standard CCSD(T)/CBS(T-Q) method. Based on the determined potential energy surfaces with the considerations of ground-state structures and specific-reaction parameters of zero-point energies, rate constants and branching ratios are calculated in a wide temperature range. The calculations show that the participation of water and DMA can lead to three-body complexes with a lower energy and influence the energy barriers, but neither of them shows the catalytic effect on the H-abstraction reactions in terms of kinetics. Additionally, the branching ratio analysis demonstrates that the product distribution is significantly altered in the presence of DMA and water.

5.
J Hazard Mater ; 477: 135368, 2024 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-39079296

RESUMEN

Tungsten (W) contamination presents emerging environmental challenges, necessitating the need to establish soil screening levels (SSLs), especially for residential soils. This study assessed the health exposure risk and derived national and regional residential SSLs for W in Chinese residential soils, incorporating machine-learning prediction of in-vitro soil W bioaccessibility. We analyzed 204 residential soil samples collected across 24 provinces, recording a wide range of W concentrations (0.01-3063.2 mg/kg). Synchrotron-based X-ray fluorescence spectroscopy, chemical extractions, and random forest modeling indicated that the key determinants of soil W bioaccessibility were soil pH, cation exchange capacity, organic matter, and clay contents. Monte Carlo simulations demonstrated that soil W contamination predominantly results in noncarcinogenic health risks to residents via oral exposure, especially in mining-affected regions. A national residential SSL (NRSSL) of 35.5 mg/kg and regional residential SSLs (RRSSLs) of 34.5-49.2 mg/kg were established. Incorporating predicted bioaccessibility increased the NRSSL to 73.8 mg/kg and the RRSSLs to 69.8-112.5 mg/kg. Southern China, which is rich in W ore, exhibited lower RRSSLs, underscoring a need for enhanced safety management. Our framework and findings provide a robust scientific foundation for future soil contamination risk assessment studies, and we present customized SSLs that can guide targeted W risk control strategies.

6.
World J Clin Cases ; 12(17): 2946-2950, 2024 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-38898826

RESUMEN

Hypoparathyroidism is one of the main complications after total thyroidectomy, severely affecting patients' quality of life. How to effectively protect parathyroid function after surgery and reduce the incidence of hypoparathyroidism has always been a key research area in thyroid surgery. Therefore, precise localization of parathyroid glands during surgery, effective imaging, and accurate surgical resection have become hot topics of concern for thyroid surgeons. In response to this clinical phenomenon, this study compared several different imaging methods for parathyroid surgery, including nanocarbon, indocyanine green, near-infrared imaging techniques, and technetium-99m methoxyisobutylisonitrile combined with gamma probe imaging technology. The advantages and disadvantages of each method were analyzed, providing scientific recommendations for future parathyroid imaging. In recent years, some related basic and clinical research has also been conducted in thyroid surgery. This article reviewed relevant literature and provided an overview of the practical application progress of various imaging techniques in parathyroid surgery.

7.
Opt Express ; 32(8): 13342-13356, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38859307

RESUMEN

Phase shifting profilometry is an important technique for reconstructing the three-dimensional (3D) geometry of objects with purely diffuse surfaces. However, it is challenging to measure the transparent objects due to the pattern aliasing caused by light refraction and multiple reflections inside the object. In this work, we analyze the aliasing fringe pattern formation for transparent objects and then, propose to learn the front surface light intensity distribution based on the formation principle by using the diffusion models for generating the non-aliased fringe patterns reflected from the front surface only. With the generated fringe patterns, the 3D shape of the transparent objects can be reconstructed via the conventional structured light. We show the feasibility and performance of the proposed method on the data of purely transparent objects that are not seen in the training stage. Moreover, we found it could be generalized to other cases with local-transparent and translucent objects, showing the potential capability of the diffusion based learnable framework in tackling the problems of transparent object reconstruction.

8.
PLoS One ; 19(6): e0303964, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38843222

RESUMEN

A Pickering emulsion was synergistically stabilised with zein nanoparticles (ZNPs) and starch nanocrystals (SNCs) to prepare it for menthol loading. After response surface optimisation of the emulsion preparation conditions, a Pickering emulsion prepared with a ZNPs:SNCs ratio of 1:1, a particle concentration of 2 wt% and a water:oil ratio of 1:1 provided the highest menthol encapsulation rate of the emulsions tested (83%) with good storage stability within 30 days. We examined the bilayer interface structure of the emulsion by optical microscopy, scanning electron microscopy, and confocal laser scanning microscopy. The results of simulated digestion experiments showed that the release rate of free fatty acid was 75.06 ± 1.23%, which ensured bioavailability. At the same time, the emulsions facilitated the slow release of menthol. Bacteriostatic studies revealed that the Pickering emulsion had a protective effect on menthol, with the most significant inhibitory effects on Escherichia coli and Staphylococcus aureus under the same conditions. Overall, this study proposes a novel approach for the application and development of l-menthol by combining it with Pickering emulsion.


Asunto(s)
Emulsiones , Escherichia coli , Mentol , Nanopartículas , Staphylococcus aureus , Almidón , Zeína , Mentol/química , Mentol/farmacología , Emulsiones/química , Nanopartículas/química , Zeína/química , Almidón/química , Staphylococcus aureus/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Tamaño de la Partícula
9.
Gastric Cancer ; 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38856768

RESUMEN

OBJECTIVE: To compare the risks of gastric cancer and other gastric diseases in patients with type-2 diabetes mellitus (T2DM) exposed to sodium-glucose cotransporter 2 inhibitors (SGLT2I), dipeptidyl peptidase-4 inhibitors (DPP4I) or glucagon-like peptide-1 receptor agonists (GLP1a). DESIGN: This was a population-based cohort study of prospectively collected data on patients with T2DM prescribed SGLT2I, DPP4I or GLP1a between January 1st 2015 and December 31st 2020 from Hong Kong. The outcomes were new-onset gastric cancer, peptic ulcer (PU), acute gastritis, non-acute gastritis, and gastroesophageal reflux disease (GERD). Propensity score matching (1:1) using the nearest neighbour search was performed, and multivariable Cox regression was applied. A three-arm comparison between SGLT2I, DPP4I and GLP1a was conducted using propensity scores with inverse probability of treatment weighting. RESULTS: A total of 62,858 patients (median age: 62.2 years old [SD: 12.8]; 55.93% males; SGLT2I: n = 23,442; DPP4I: n = 39,416) were included. In the matched cohort, the incidence of gastric cancer was lower in SGLT2I (Incidence rate per 1000 person-year, IR: 0.32; 95% confidence interval, CI 0.23-0.43) than in DPP4I (IR per 1000 person-year: 1.22; CI 1.03-1.42) users. Multivariable Cox regression found that SGLT2I use was associated with lower risks of gastric cancer (HR 0.30; 95% CI 0.19-0.48), PU, acute gastritis, non-acute gastritis, and GERD (p < 0.05) compared to DPP4I use. In the three-arm analysis, GLP1a use was associated with higher risks of gastric cancer and GERD compared to SGLT2I use. CONCLUSIONS: The use of SGLT2I was associated with lower risks of new-onset gastric cancer, PU, acute gastritis, non-acute gastritis, and GERD after matching and adjustments compared to DPP4I use. SGLT2I use was associated with lower risks of GERD and gastric cancer compared to GLP1a use.

10.
ACS Omega ; 9(24): 26050-26057, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38911733

RESUMEN

Adsorption is a promising technology to remove perfluoroalkyl substances (PFAS), including perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), from contaminated water. Although a large number of materials have been evaluated for PFAS adsorption, guidelines that can facilitate the rational design and selection of adsorbents have not been established due to the lack of a mechanistic understanding on the molecular level. Using a novel interpretation of the Freundlich isotherm, this study identifies halogen bonding as the main mechanism controlling perfluoroalkyl adsorption by using a materiomic approach that compares the electrostatic polarities of a variety of carbon, polymer, and mineral-based materials reported in the literature. Comparisons show that both PFOS and PFOA are favorably adsorbed by materials containing high densities of π electrons, lone electron pairs, and negative charges, consistent with the formation of halogen bonding between the positive σ-hole of fluorine as a Lewis acid and a nucleophilic solid as a Lewis base. The identification of this previously unappreciated noncovalent bonding mechanism offers fresh insight into the search of suitable materials for perfluoroalkyl adsorption.

11.
Sci China Life Sci ; 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38913236

RESUMEN

The BMP signaling pathway plays a crucial role in regulating early embryonic development and tissue homeostasis. SMAD6 encodes a negative regulator of BMP, and rare variants of SMAD6 are recurrently found in individuals with birth defects. However, we observed that a subset of rare pathogenic variants of SMAD6 consistently exhibited positive regulatory effects instead of the initial negative effects on the BMP signaling pathway. We sought to determine whether these SMAD6 variants have common pathogenic mechanisms. Here, we showed that pathogenic SMAD6 variants accompanying this functional reversal exhibit similar increases in deamidation. Mechanistically, increased deamidation of SMAD6 variants promotes the accumulation of the BMP receptor BMPR1A and the formation of new complexes, both of which lead to BMP signaling pathway activation. Specifically, two residues, N262 and N404, in SMAD6 were identified as the crucial sites of deamidation, which was catalyzed primarily by glutamine-fructose-6-phosphate transaminase 2 (GFPT2). Additionally, treatment of cells harboring SMAD6 variants with a deamidase inhibitor restored the inhibitory effect of SMAD6 on the BMP signaling pathway. Conversely, when wild-type SMAD6 was manually simulated to mimic the deamidated state, the reversed function of activating BMP signaling was reproduced. Taken together, these findings show that deamidation of SMAD6 plays a crucial role in the functional reversal of BMP signaling activity, which can be induced by a subset of various SMAD6 variants. Our study reveals a common pathogenic mechanism shared by these variants and provides a potential strategy for preventing birth defects through deamidation regulation, which might prevent the off-target effects of gene editing.

12.
Biosensors (Basel) ; 14(6)2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38920598

RESUMEN

A microfluidic sweat monitoring patch that collects human sweat for a long time is designed to achieve the effect of detecting the rise and fall of human sweat glucose over a long period of time by increasing the use time of a single patch. Five collection pools, four serpentine channels, and two different valves are provided. Among them, the three-dimensional valve has a large burst pressure as a balance between the internal and external air pressures of the patch. The bursting pressure of the two-dimensional diverter valve is smaller than that of the three-dimensional gas valve, and its role is to control the flow direction of the liquid. Through plasma hydrophilic treatment of different durations, the optimal hydrophilic duration is obtained. The embedded chromogenic disc detects the sweat glucose value at two adjacent time intervals and compares the information of the human body to increase or reduce glucose. The patch has good flexibility and can fit well with human skin, and because polydimethylsiloxane (PDMS) has good light transmission, it reduces the measurement error caused by the color-taking process and makes the detection results more accurate.


Asunto(s)
Sudor , Humanos , Sudor/química , Hipoglucemia , Glucosa/análisis , Técnicas Biosensibles , Microfluídica , Dimetilpolisiloxanos/química , Glucemia/análisis
13.
Anal Bioanal Chem ; 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38877149

RESUMEN

Identification of O-glycopeptides from tandem mass spectrometry data is complicated by the near complete dissociation of O-glycans from the peptide during collisional activation and by the combinatorial explosion of possible glycoforms when glycans are retained intact in electron-based activation. The recent O-Pair search method provides an elegant solution to these problems, using a collisional activation scan to identify the peptide sequence and total glycan mass, and a follow-up electron-based activation scan to localize the glycosite(s) using a graph-based algorithm in a reduced search space. Our previous O-glycoproteomics methods with MSFragger-Glyco allowed for extremely fast and sensitive identification of O-glycopeptides from collisional activation data but had limited support for site localization of glycans and quantification of glycopeptides. Here, we report an improved pipeline for O-glycoproteomics analysis that provides proteome-wide, site-specific, quantitative results by incorporating the O-Pair method as a module within FragPipe. In addition to improved search speed and sensitivity, we add flexible options for oxonium ion-based filtering of glycans and support for a variety of MS acquisition methods and provide a comparison between all software tools currently capable of O-glycosite localization in proteome-wide searches.

14.
Cell Death Dis ; 15(6): 448, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38918408

RESUMEN

Multiple sevoflurane exposures may damage the developing brain. The neuroprotective function of dexmedetomidine has been widely confirmed in animal experiments and human studies. However, the effect of dexmedetomidine on the glymphatic system has not been clearly studied. We hypothesized that dexmedetomidine could alleviate sevoflurane-induced circulatory dysfunction of the glymphatic system in young mice. Six-day-old C57BL/6 mice were exposed to 3% sevoflurane for 2 h daily, continuously for 3 days. Intraperitoneal injection of either normal saline or dexmedetomidine was administered before every anaesthesia. Meanwhile the circulatory function of glymphatic system was detected by tracer injection at P8 and P32. On P30-P32, behavior tests including open field test, novel object recognition test, and Y-maze test were conducted. Primary astrocyte cultures were established and treated with the PI3K activator 740Y-P, dexmedetomidine, and small interfering RNA (siRNA) to silence ΔFosB. We propose for the first time that multiple exposure to sevoflurane induces circulatory dysfunction of the glymphatic system in young mice. Dexmedetomidine improves the circulatory capacity of the glymphatic system in young mice following repeated exposure to sevoflurane through the PI3K/AKT/ΔFosB/AQP4 signaling pathway, and enhances their long-term learning and working memory abilities.


Asunto(s)
Acuaporina 4 , Dexmedetomidina , Sistema Glinfático , Ratones Endogámicos C57BL , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Sevoflurano , Transducción de Señal , Animales , Dexmedetomidina/farmacología , Sevoflurano/farmacología , Sevoflurano/efectos adversos , Sistema Glinfático/efectos de los fármacos , Sistema Glinfático/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratones , Fosfatidilinositol 3-Quinasas/metabolismo , Acuaporina 4/metabolismo , Acuaporina 4/genética , Transducción de Señal/efectos de los fármacos , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Masculino
16.
Biomed Pharmacother ; 175: 116739, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38759288

RESUMEN

BACKGROUND: Ketamine, as a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, was originally used in general anesthesia. Epidemiological data show that ketamine has become one of the most commonly abused drugs in China. Ketamine administration might cause cognitive impairment; however, its molecular mechanism remains unclear. The glymphatic system is a lymphoid system that plays a key role in metabolic waste removal and cognitive regulation in the central nervous system. METHODS: Focusing on the glymphatic system, this study evaluated the behavioral performance and circulatory function of the glymphatic system by building a short-term ketamine administration model in mice, and detected the expression levels of the 5-HT2c receptor, ΔFosb, Pten, Akt, and Aqp4 in the hippocampus. Primary astrocytes were cultured to verify the regulatory relationships among related indexes using a 5-HT2c receptor antagonist, a 5-HT2c receptor short interfering RNA (siRNA), and a ΔFosb siRNA. RESULTS: Ketamine administration induced ΔFosb accumulation by increasing 5-HT2c receptor expression in mouse hippocampal astrocytes and primary astrocytes. ΔFosb acted as a transcription factor to recognize the AATGATTAAT bases in the 5' regulatory region of the Aqp4 gene (-1096 bp to -1087 bp), which inhibited Aqp4 expression, thus causing the circulatory dysfunction of the glymphatic system, leading to cognitive impairment. CONCLUSIONS: Although this regulatory mechanism does not involve the Pten/Akt pathway, this study revealed a new mechanism of ketamine-induced cognitive impairment in non-neuronal systems, and provided a theoretical basis for the safety of clinical treatment and the effectiveness of withdrawal.


Asunto(s)
Astrocitos , Disfunción Cognitiva , Sistema Glinfático , Hipocampo , Ketamina , Animales , Ketamina/farmacología , Ketamina/toxicidad , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/metabolismo , Ratones , Masculino , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Sistema Glinfático/efectos de los fármacos , Sistema Glinfático/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Acuaporina 4/metabolismo , Acuaporina 4/genética , Receptor de Serotonina 5-HT2C/metabolismo , Receptor de Serotonina 5-HT2C/genética , Ratones Endogámicos C57BL , Células Cultivadas , Proteínas Proto-Oncogénicas c-fos/metabolismo , Proteínas Proto-Oncogénicas c-fos/genética , Fosfohidrolasa PTEN/metabolismo , Fosfohidrolasa PTEN/genética
17.
Nanotechnology ; 35(32)2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38701763

RESUMEN

Advanced photocatalysts are highly desired to activate the photocatalytic CO2reduction reaction (CO2RR) with low concentration. Herein, the NiSn(OH)6with rich surface lattice hydroxyls was synthesized to boost the activity directly under the natural air. Results showed that terminal Ni-OH could serve as donors to feed protons and generate oxygen vacancies (VO), thus beneficial to convert the activated CO2(HCO3-) mainly into CO (5.60µmol g-1) in the atmosphere. It was flexible and widely applicable for a stable CO2RR from high pure to air level free of additionally adding H2O reactant, and higher than the traditional gas-liquid-solid (1.58µmol g-1) and gas-solid (4.07µmol g-1) reaction system both using high pure CO2and plenty of H2O. The strong hydrophilia by the rich surface hydroxyls allowed robust H2O molecule adsorption and dissociation at VOsites to achieve the Ni-OH regeneration, leading to a stable CO yield (11.61µmol g-1) with the enriched renewable VOregardless of the poor CO2and H2O in air. This work opens up new possibilities for the practical application of natural photosynthesis.

18.
Sci Bull (Beijing) ; 69(14): 2260-2272, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-38702277

RESUMEN

Heparan sulfate proteoglycan 2 (HSPG2) gene encodes the matrix protein Perlecan, and genetic inactivation of this gene creates mice that are embryonic lethal with severe neural tube defects (NTDs). We discovered rare genetic variants of HSPG2 in 10% cases compared to only 4% in controls among a cohort of 369 NTDs. Endorepellin, a peptide cleaved from the domain V of Perlecan, is known to promote angiogenesis and autophagy in endothelial cells. The roles of enderepellin in neurodevelopment remain unclear so far. Our study revealed that endorepellin can migrate to the neuroepithelial cells and then be recognized and bind with the neuroepithelia receptor neurexin in vivo. Through the endocytic pathway, the interaction of endorepellin and neurexin physiologically triggers autophagy and appropriately modulates the differentiation of neural stem cells into neurons as a blocker, which is necessary for normal neural tube closure. We created knock-in (KI) mouse models with human-derived HSPG2 variants, using sperm-like stem cells that had been genetically edited by CRISPR/Cas9. We realized that any HSPG2 variants that affected the function of endorepellin were considered pathogenic causal variants for human NTDs given that the severe NTD phenotypes exhibited by these KI embryos occurred in a significantly higher response frequency compared to wildtype embryos. Our study provides a paradigm for effectively confirming pathogenic mutations in other genetic diseases. Furthermore, we demonstrated that using autophagy inhibitors at a cellular level can repress neuronal differentiation. Therefore, autophagy agonists may prevent NTDs resulting from failed autophagy maintenance and neuronal over-differentiation caused by deleterious endorepellin variants.


Asunto(s)
Autofagia , Proteoglicanos de Heparán Sulfato , Defectos del Tubo Neural , Animales , Ratones , Proteoglicanos de Heparán Sulfato/metabolismo , Proteoglicanos de Heparán Sulfato/genética , Humanos , Defectos del Tubo Neural/genética , Defectos del Tubo Neural/metabolismo , Defectos del Tubo Neural/patología , Tubo Neural/metabolismo , Tubo Neural/embriología , Tubo Neural/patología , Células-Madre Neurales/metabolismo , Células Neuroepiteliales/metabolismo , Femenino , Masculino , Modelos Animales de Enfermedad
19.
Mater Today Bio ; 25: 101007, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38779617

RESUMEN

Zirconia faces challenges in dental implant applications due to its inherent biological inertness, which compromises osseointegration, a critical factor for the long-term success of implants that rely heavily on specific cell adhesion and enhanced osteogenic activity. Here, we fabricated a dual-functional coating that incorporates strontium ions, aimed at enhancing osteogenic activity, along with an integrin-targeting sequence to improve cell adhesion by mussel byssus-inspired surface chemistry. The results indicated that although the integrin-targeting sequence at the interface solely enhances osteoblast adhesion without directly increasing osteogenic activity, its synergistic interaction with the continuously released strontium ions from the coating, as compared to the release of strontium ions alone, significantly enhances the overall osteogenic effect. More importantly, compared to traditional polydopamine surface chemistry, the coating surface is enriched with amino groups capable of undergoing various chemical reactions and exhibits enhanced stability and aesthetic appeal. Therefore, the synergistic interplay between strontium and the functionally customizable surface offers considerable potential to improve the success of zirconia implantation.

20.
Eur Heart J Digit Health ; 5(3): 247-259, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38774384

RESUMEN

Aims: Electrocardiogram (ECG) is widely considered the primary test for evaluating cardiovascular diseases. However, the use of artificial intelligence (AI) to advance these medical practices and learn new clinical insights from ECGs remains largely unexplored. We hypothesize that AI models with a specific design can provide fine-grained interpretation of ECGs to advance cardiovascular diagnosis, stratify mortality risks, and identify new clinically useful information. Methods and results: Utilizing a data set of 2 322 513 ECGs collected from 1 558 772 patients with 7 years follow-up, we developed a deep-learning model with state-of-the-art granularity for the interpretable diagnosis of cardiac abnormalities, gender identification, and hypertension screening solely from ECGs, which are then used to stratify the risk of mortality. The model achieved the area under the receiver operating characteristic curve (AUC) scores of 0.998 (95% confidence interval (CI), 0.995-0.999), 0.964 (95% CI, 0.963-0.965), and 0.839 (95% CI, 0.837-0.841) for the three diagnostic tasks separately. Using ECG-predicted results, we find high risks of mortality for subjects with sinus tachycardia (adjusted hazard ratio (HR) of 2.24, 1.96-2.57), and atrial fibrillation (adjusted HR of 2.22, 1.99-2.48). We further use salient morphologies produced by the deep-learning model to identify key ECG leads that achieved similar performance for the three diagnoses, and we find that the V1 ECG lead is important for hypertension screening and mortality risk stratification of hypertensive cohorts, with an AUC of 0.816 (0.814-0.818) and a univariate HR of 1.70 (1.61-1.79) for the two tasks separately. Conclusion: Using ECGs alone, our developed model showed cardiologist-level accuracy in interpretable cardiac diagnosis and the advancement in mortality risk stratification. In addition, it demonstrated the potential to facilitate clinical knowledge discovery for gender and hypertension detection which are not readily available.

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