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1.
Stat Methods Med Res ; : 9622802241242317, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38592341

RESUMO

The Fellegi-Sunter model is a latent class model widely used in probabilistic linkage to identify records that belong to the same entity. Record linkage practitioners typically employ all available matching fields in the model with the premise that more fields convey greater information about the true match status and hence result in improved match performance. In the context of model-based clustering, it is well known that such a premise is incorrect and the inclusion of noisy variables could compromise the clustering. Variable selection procedures have therefore been developed to remove noisy variables. Although these procedures have the potential to improve record matching, they cannot be applied directly due to the ubiquity of the missing data in record linkage applications. In this paper, we modify the stepwise variable selection procedure proposed by Fop, Smart, and Murphy and extend it to account for missing data common in record linkage. Through simulation studies, our proposed method is shown to select the correct set of matching fields across various settings, leading to better-performing algorithms. The improved match performance is also seen in a real-world application. We therefore recommend the use of our proposed selection procedure to identify informative matching fields for probabilistic record linkage algorithms.

2.
ACS Biomater Sci Eng ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38564666

RESUMO

Despite being a weaker metal, zinc has become an increasingly popular candidate for biodegradable implant applications due to its suitable corrosion rate and biocompatibility. Previous studies have experimented with various alloy elements to improve the overall mechanical performance of pure Zn without compromising the corrosion performance and biocompatibility; however, the thermal stability of biodegradable Zn alloys has not been widely studied. In this study, TiC nanoparticles were introduced for the first time to a Zn-Al-Cu system. After hot rolling, TiC nanoparticles were uniformly distributed in the Zn matrix and effectively enabled phase control during solidification. The Zn-Cu phase, which was elongated and sharp in the reference alloy, became globular in the nanocomposite. The strength of the alloy, after introducing TiC nanoparticles, increased by 31% from 259.7 to 340.3 MPa, while its ductility remained high at 49.2% elongation to failure. Fatigue performance also improved greatly by adding TiC nanoparticles, increasing the fatigue limit by 47.6% from 44.7 to 66 MPa. Furthermore, TiC nanoparticles displayed excellent phase control capability during body-temperature aging. Without TiC restriction, Zn-Cu phases evolved into dendritic morphologies, and the Al-rich eutectic grew thicker at grain boundaries. However, both Zn-Cu and Al-rich eutectic phases remained relatively unchanged in shape and size in the nanocomposite. A combination of exceptional tensile properties, improved fatigue performance, better long-term stability with a suitable corrosion rate, and excellent biocompatibility makes this new Zn-Al-Cu-TiC material a promising candidate for biodegradable stents and other biodegradable applications.

3.
Appl Clin Inform ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38508580

RESUMO

BACKGROUND: Patient data is fragmented across multiple repositories, yielding suboptimal and costly care. Record linkage algorithms are widely accepted solutions for improving completeness of patient records. However, studies often fail to fully describe their linkage techniques. Further, while many frameworks evaluate record linkage methods, few focus on producing gold standard datasets. This highlights a need to assess these frameworks and their real-world performance. OBJECTIVE: We use real-world datasets and expand upon previous frameworks to evaluate a consistent approach to the manual review of gold standard datasets and measure its impact on algorithm performance. METHODS: We applied the framework, which includes elements for data description, reviewer training and adjudication, and software and reviewer descriptions, to four datasets. Record-pairs were formed and 15,000 records were randomly sampled from these pairs. After training, two reviewers determined match status for each record-pair. If reviewers disagreed, a third reviewer was used for final adjudication. RESULTS: Between the four datasets, the percent discordant rate ranged from 1.8-13.6%. While reviewers' discordance rate typically ranged between 1% and 5%, one exhibited a 59% discordance rate, showing the importance of the third reviewer. The original analysis was compared to three sensitivity analyses. The original analysis most often exhibited the highest predictive values compared to the sensitivity analyses. CONCLUSION: Reviewers vary in their assessment of a gold standard, which can lead to variances in estimates for matching performance. Our analysis demonstrates how a multi-reviewer process can be applied to create gold standards, identify reviewer discrepancies, and evaluate algorithm performance.

4.
Sci Rep ; 14(1): 6072, 2024 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-38480826

RESUMO

Blood transfusions from convalescent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infected patients could be used to treat patients with severe infections or immunocompromised patients. However, it is necessary to select the optimal donors to maximize the utilization of resources. In this study, we investigated the associations among body mass index (BMI), tobacco smoking, exercise frequency and duration, and alcohol consumption with the SARS-CoV-2 immunoglobulin-G (IgG) antibody titer levels with in the Chinese convalescent blood donor population. Here we show that BMI, smoking habits, and exercise frequency appear to be predictive factors for IgG levels in convalescent male blood donors. However, these variables were not observed as predictive of IgG levels in female convalescent blood donors. The findings could be used to optimize the screening for potential blood donors to treat immunocompromised or severely ill COVID-19 patients.


Assuntos
COVID-19 , Humanos , Masculino , Feminino , SARS-CoV-2 , Doadores de Sangue , Estudos Transversais , Imunização Passiva , Soroterapia para COVID-19 , Anticorpos Antivirais , Imunoglobulina G , China
5.
ACS Appl Mater Interfaces ; 16(7): 9532-9543, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38345942

RESUMO

Flexible piezoresistive sensors with a porous structure that are used in the field of speech recognition are seldom characterized by both high sensitivity and ease of preparation. In this study, a piezoresistive sensor with a porous structure that is both highly sensitive and can be prepared by using a simple method is proposed for speech recognition. The preparation process utilizes the interaction of bubbles generated by ethanol evaporation and active agents with polydimethylsiloxane to produce a porous flexible substrate. This preparation process requires neither templates nor harsh experimental conditions such as a low temperature and a low pressure. Furthermore, the prepared piezoresistive sensor has excellent properties, such as a high sensitivity (27.6 kPa-1), a satisfactory response time (800 µs), and a good stability (10,000 cycles). When used for speech recognition, more than 1500 vocalizations and silent speech signals obtained from subjects saying numbers from "0" to "9" were collected by the sensor for training a convolutional neural network model. The average accuracy of the recognition reached 94.8%. The simple preparation process and the excellent performance of the prepared flexible piezoresistive sensor endow it with a wide application prospect in the field of speech recognition.


Assuntos
Percepção da Fala , Fala , Humanos , Porosidade , Temperatura Baixa , Etanol
6.
JAMA Netw Open ; 7(1): e2350511, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38198141

RESUMO

Importance: More than 80% of patients who present to the emergency department (ED) with acute heart failure (AHF) are hospitalized. With more than 1 million annual hospitalizations for AHF in the US, safe and effective alternatives are needed. Care for AHF in short-stay units (SSUs) may be safe and more efficient than hospitalization, especially for lower-risk patients, but randomized clinical trial data are lacking. Objective: To compare the effectiveness of SSU care vs hospitalization in lower-risk patients with AHF. Design, Setting, and Participants: This multicenter randomized clinical trial randomly assigned low-risk patients with AHF 1:1 to SSU or hospital admission from the ED. Patients received follow-up at 30 and 90 days post discharge. The study began December 6, 2017, and was completed on July 22, 2021. The data were analyzed between March 27, 2020, and November 11, 2023. Intervention: Randomized post-ED disposition to less than 24 hours of SSU care vs hospitalization. Main Outcomes and Measures: The study was designed to detect at least 1-day superiority for a primary outcome of days alive and out of hospital (DAOOH) at 30-day follow-up for 534 participants, with an allowance of 10% participant attrition. Due to the COVID-19 pandemic, enrollment was truncated at 194 participants. Before unmasking, the primary outcome was changed from DAOOH to an outcome with adequate statistical power: quality of life as measured by the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12). The KCCQ-12 scores range from 0 to 100, with higher scores indicating better quality of life. Results: Of the 193 patients enrolled (1 was found ineligible after randomization), the mean (SD) age was 64.8 (14.8) years, 79 (40.9%) were women, and 114 (59.1%) were men. Baseline characteristics were balanced between arms. The mean (SD) KCCQ-12 summary score between the SSU and hospitalization arms at 30 days was 51.3 (25.7) vs 45.8 (23.8) points, respectively (P = .19). Participants in the SSU arm had 1.6 more DAOOH at 30-day follow-up than those in the hospitalization arm (median [IQR], 26.9 [24.4-28.8] vs 25.4 [22.0-27.7] days; P = .02). Adverse events were uncommon and similar in both arms. Conclusions and Relevance: The findings show that the SSU strategy was no different than hospitalization with regard to KCCQ-12 score, superior for more DAOOH, and safe for lower-risk patients with AHF. These findings of lower health care utilization with the SSU strategy need to be definitively tested in an adequately powered study. Trial Registration: ClinicalTrials.gov Identifier: NCT03302910.


Assuntos
Insuficiência Cardíaca , Alta do Paciente , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Assistência ao Convalescente , Serviço Hospitalar de Emergência , Insuficiência Cardíaca/terapia , Hospitalização , Pandemias , Qualidade de Vida , Idoso
7.
J Inflamm Res ; 17: 91-100, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38204989

RESUMO

Intervertebral disc degeneration is a chronic degenerative disease caused by the interaction of genetic and environmental factors, mainly manifested as lower back pain. At present, the diagnosis of intervertebral disc degeneration mainly relies on imaging. However, early intervertebral disc degeneration is usually insidious, and there is currently a lack of relevant clinical biomarkers that can reliably reflect early disease progression. Pyroptosis is a regulatory form of cell death triggered by the activation of inflammatory bodies and caspase, which can induce the formation of plasma membrane pores and cell swelling or lysis. Previous studies have shown that during the progression of intervertebral disc degeneration, sustained activation of inflammasomes leads to nuclear cell pyroptosis, which can occur in the early stages of intervertebral disc degeneration. Moreover, intervertebral disc nucleus pulposus cells adapt to the external environment through autophagy and maintain cellular homeostasis and studying the mechanism of autophagy in IDD and intervening in its pathological and physiological processes can provide new ideas for the clinical treatment of IDD. This review analyzes the effects of pyroptosis and autophagy on IDD by reviewing relevant literature in recent years, in order to explore the relationship between pyroptosis, autophagy and IDD.

8.
Dalton Trans ; 53(4): 1449-1459, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-37909312

RESUMO

Discrete spin crossover (SCO) tetranuclear cages are a unique class of materials that have potential use in next-generation molecular recognition and sensing. In this work, two new edge-bridged SCO FeII4L6 (L = 2,7-bis(((E)-pyridin-2-ylmethylene)amino)benzo[lmn] [3,8]phenanthroline-1,3,6,8(2H,7H)-tetraone) supramolecular cages with different counter anions: ClO4- (2) and CF3SO3- (3) were constructed via subcomponent self-assembly to investigate both solvent and anion influences on their magnetic properties and compare them to cage 1 with a BF4- anion. Pyridyl-hydrazone bidentate ligand scaffolds were employed to replace the 'classical' imidazole/thiazolyl-imine coordination units to induce SCO behaviour in these cages. 2 and 3 were structurally characterized by single-crystal X-ray diffraction analysis and electrospray ionization time-of-flight mass spectrometry. Magnetic susceptibilities of 1-3 and 1-3·desolvated indicate that the solvents' presence is in favor of the low-spin (LS) state. While different counter anions in 1-3·desolvated affect the spin-state configurations of the four FeII metal centers. According to the 57Fe Mössbauer spectral analysis, the spin-state distributions in 1-3 at 80 K are [2 high-spin (HS)-2LS], [1HS-3LS] and [2HS-2LS], respectively and density functional theory calculations were employed to investigate the reasons. These findings provide insights to regulate the spin-state versatility of SCO FeII cage systems in the solid state.

9.
J Cardiol ; 83(2): 121-129, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37579872

RESUMO

BACKGROUND: Lung ultrasound congestion scoring (LUS-CS) is a congestion severity biomarker. The BLUSHED-AHF trial demonstrated feasibility for LUS-CS-guided therapy in acute heart failure (AHF). We investigated two questions: 1) does change (∆) in LUS-CS from emergency department (ED) to hospital-discharge predict patient outcomes, and 2) is the relationship between in-hospital decongestion and adverse events moderated by baseline risk-factors at admission? METHODS: We performed a secondary analysis of 933 observations/128 patients from 5 hospitals in the BLUSHED-AHF trial receiving daily LUS. ∆LUS-CS from ED arrival to inpatient discharge (scale -160 to +160, where negative = improving congestion) was compared to a primary outcome of 30-day death/AHF-rehospitalization. Cox regression was used to adjust for mortality risk at admission [Get-With-The-Guidelines HF risk score (GWTG-RS)] and the discharge LUS-CS. An interaction between ∆LUS-CS and GWTG-RS was included, under the hypothesis that the association between decongestion intensity (by ∆LUS-CS) and adverse outcomes would be stronger in admitted patients with low-mortality risk but high baseline congestion. RESULTS: Median age was 65 years, GWTG-RS 36, left ventricular ejection fraction 36 %, and ∆LUS-CS -20. In the multivariable analysis ∆LUS-CS was associated with event-free survival (HR = 0.61; 95 % CI: 0.38-0.97), while discharge LUS-CS (HR = 1.00; 95%CI: 0.54-1.84) did not add incremental prognostic value to ∆LUS-CS alone. As GWTG-RS rose, benefits of LUS-CS reduction attenuated (interaction p < 0.05). ∆LUS-CS and event-free survival were most strongly correlated in patients without tachycardia, tachypnea, hypotension, hyponatremia, uremia, advanced age, or history of myocardial infarction at ED/baseline, and those with low daily loop diuretic requirements. CONCLUSIONS: Reduction in ∆LUS-CS during AHF treatment was most associated with improved readmission-free survival in heavily congested patients with otherwise reassuring features at admission. ∆LUS-CS may be most useful as a measure to ensure adequate decongestion prior to discharge, to prevent early readmission, rather than modify survival.


Assuntos
Insuficiência Cardíaca , Edema Pulmonar , Idoso , Humanos , Pulmão/diagnóstico por imagem , Prognóstico , Volume Sistólico , Função Ventricular Esquerda
10.
Clin Genitourin Cancer ; 22(1): e31-e37.e1, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37482523

RESUMO

INTRODUCTION: Somatic mutations in the Wnt signaling gene Adenomatous Polyposis Coli (APC) promote metastatic prostate cancer (PCa) progression. Less is known regarding the impact of germline APC mutations on PCa outcomes. We sought to investigate the prevalence of aggressive variant PCa (AVPC) and treatment-emergent neuroendocrine PCa (t-NEPC) in patients with the germline APC I1307K variant, an alteration found in 7% of Ashkenazi Jewish men. MATERIALS AND METHODS: We report a retrospective cohort study comparing patients with PCa and either APC I1307K germline mutation, APC somatic mutations, or unselected patients. Proportions of patients with AVPC among all the cases were estimated along with 95% Clopper-Pearson exact confidence intervals (CI). Odds ratios with 95% CI were provided for the prevalence of t-NEPC and AVPC in patients with germline APC I1307K compared to patients with frameshift alterations in APC. RESULTS: From 2016-2022, 18 patients with PCa at 3 institutions with the germline APC (I1307K) mutation were identified. Clinically-defined AVPC was found in 8 of the 15 cases with metastatic disease (53%; 95% CI: 26%-79%). Combined somatic alterations in two or more of RB1, TP53 or PTEN (molecularly-defined AVPC) were found in 5/18 cases (28%; 95% CI: 10%-54%). When compared to 20 patients with APC somatic frameshift mutations, patients with the germline APC I1307K variant had a significantly increased risk of AVPC (OR 7.2; 95% CI 1.27, 40.68). CONCLUSION: PCa that develops in the presence of the germline APC I1307K mutation appear to be enriched for clinically-defined and molecularly-defined AVPC and in particular, for t-NEPC.


Assuntos
Polipose Adenomatosa do Colo , Neoplasias Colorretais , Neoplasias da Próstata , Masculino , Humanos , Mutação em Linhagem Germinativa , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Estudos Retrospectivos , Polipose Adenomatosa do Colo/genética , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Células Germinativas/patologia
11.
Nephrol Dial Transplant ; 39(2): 264-276, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-37468453

RESUMO

BACKGROUND: 25-hydroxyvitamin D can undergo C-3 epimerization to produce 3-epi-25(OH)D3. 3-epi-25(OH)D3 levels decline in chronic kidney disease (CKD), but its role in regulating the cardiovascular system is unknown. Herein, we examined the relationship between 3-epi-25(OH)D3, and cardiovascular functional and structural endpoints in patients with CKD. METHODS: We examined n = 165 patients with advanced CKD from the Cardiopulmonary Exercise Testing in Renal Failure and After Kidney Transplantation (CAPER) study cohort, including those who underwent kidney transplant (KTR, n = 76) and waitlisted patients who did not (NTWC, n = 89). All patients underwent cardiopulmonary exercise testing and echocardiography at baseline, 2 months and 12 months. Serum 3-epi-25(OH)D3 was analyzed by liquid chromatography-tandem mass spectrometry. RESULTS: Patients were stratified into quartiles of baseline 3-epi-25(OH)D3 (Q1: <0.4 ng/mL, n = 51; Q2: 0.4 ng/mL, n = 26; Q3: 0.5-0.7 ng/mL, n = 47; Q4: ≥0.8 ng/mL, n = 41). Patients in Q1 exhibited lower peak oxygen uptake [VO2Peak = 18.4 (16.2-20.8) mL/min/kg] compared with Q4 [20.8 (18.6-23.2) mL/min/kg; P = .009]. Linear mixed regression model showed that 3-epi-25(OH)D3 levels increased in KTR [from 0.47 (0.30) ng/mL to 0.90 (0.45) ng/mL] and declined in NTWC [from 0.61 (0.32) ng/mL to 0.45 (0.29) ng/mL; P < .001]. Serum 3-epi-25(OH)D3 was associated with VO2Peak longitudinally in both groups [KTR: ß (standard error) = 2.53 (0.56), P < .001; NTWC: 2.73 (0.70), P < .001], but was not with left ventricular mass or arterial stiffness. Non-epimeric 25(OH)D3, 24,25(OH)2D3 and the 25(OH)D3:24,25(OH)2D3 ratio were not associated with any cardiovascular outcome (all P > .05). CONCLUSIONS: Changes in 3-epi-25(OH)D3 levels may regulate cardiovascular functional capacity in patients with advanced CKD.


Assuntos
Sistema Cardiovascular , Transplante de Rim , Insuficiência Renal Crônica , Humanos , Vitamina D , Vitaminas , Insuficiência Renal Crônica/cirurgia
12.
Photodiagnosis Photodyn Ther ; 45: 103939, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38161035

RESUMO

OBJECTIVE: To investigate macula structure thickness and volume changes in patients with moyamoya disease (MMD). METHOD: In this cross-sectional study, we used artificial intelligence (AI) -assisted optical coherence tomography (OCT) to analyze the thickness and volume of macula in Moyamoya patients. ETDRS zoning divides the macula into nine different regions. In 15 patients with radial scanning OCT, the average thickness and volume of retina, RNFL, GCL, and choroid in these regions were measured. In 30 patients with radial or horizontal scanning OCT, based on the anatomical structure, the macula is divided into seven segments. Mean Sattler layer-choriocapillaris complex thickness (SLCCT), Haller layer thickness, and total choroidal thickness were measured for each segment using AI-assisted OCT. RESULTS: We recruited 30 patients (59 eyes) with MMD. In the 15 patients (29 eyes) who underwent radial scanning OCT, no significant change in retina, RNFL, GCL, and choroidal thickness was identified between the two groups (p > 0.05). There was no significant change in retina, RNFL, or choroidal volume between the two groups in different ETDRS macula regions (p > 0.05). The GCL volume in the macula's inner ring nasal portion (IN) was significantly lower. SLCCTs were considerably reduced in six macula regions in moyamoya groups (p < 0.05). There was no statistically significant change in Haller layer thickness. Only the nasal perifovea (PE_N) exhibited a significant variation in choroidal thickness. The Moyamoya group showed reduced choroidal thickness in PE_N segment. CONCLUSION: In patients with MMD, there is thinning of the Sattler layer-choriocapillaris complex in the choroid.


Assuntos
Doença de Moyamoya , Fotoquimioterapia , Humanos , Inteligência Artificial , Tomografia de Coerência Óptica/métodos , Doença de Moyamoya/diagnóstico por imagem , Estudos Transversais , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes
13.
ACS Omega ; 8(48): 46127-46143, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38075791

RESUMO

The Qingshui Basin in China is a hotspot for coalbed methane exploration, and the selection and arrangement of the surface well are crucial engineering issues for the drainage process. To address this, the present study establishes several novel coal permeability models based on the strain relationship of representative elementary volumes (REV) and discusses the evolution mechanism of permeability. Moreover, the spatiotemporal evolution patterns of permeability during the drainage process are analyzed, and a methodology is presented for the selection and arrangement of a surface well based on the predrainage time at the working face. The results indicate that in the permeability model, the volumetric strain of REV is linearly correlated with the volumetric strain of their respective fractures, with the correlation coefficient representing the initial fracture porosity. The variation pattern of coal permeability near surface wells during the drainage process is closely aligned with the trend of the adsorption strain. Additionally, the selection and arrangement of surface wells are correlated with the predrainage time at the working face, including the minimum number and location of vertical wells, as well as the optimal length of horizontal wells. The research findings provide valuable insights into enhancing the efficiency of coalbed methane drainage.

14.
Huan Jing Ke Xue ; 44(12): 6621-6629, 2023 Dec 08.
Artigo em Chinês | MEDLINE | ID: mdl-38098389

RESUMO

The cement industry faces great pressure from the targets of carbon peak and carbon neutrality. CO2capture, geological utilization, and storage(CCUS) technology is crucial for CO2 mitigation in large-scale fossil-based industries. An integrated techno-economic assessment model of CCUS was improved here to assess the potential of CCUS retrofits in the cement industry in China, and the cost curve or supply curve of CCUS in the cement industry was obtained. The model set up ten scenarios from four aspects:source-sink matching distance, capture rate, CCUS technology, and technical level. The cement enterprise screening, site screening, techno-economic evaluation, and source-sink matching of CCUS were completed to answer some key problems in realizing low-carbon development via CCUS, such as enterprise inventory, storage site, emission reduction scale, and cost range. Under the scenario of 250 km matching distance, 85% net capture rate, CO2-enhanced water recovery technology, and current technical level, 44% of cement enterprises reduced carbon emission via CCUS, the cumulative capacity reached 625 million tons per year, and the levelized cost was 290-1838 yuan·t-1. The projects with a levelized cost of fewer than 600 yuan·t-1 accounted for 77% and could reduce CO2 emission by 564 million tons annually. The projects whose levelized cost was less than 400 yuan·t-1 could reduce CO2 by 199 million tons per year. When the coupling of CO2-enhanced oil recovery and CO2-enhanced water recovery technology was considered, the levelized cost was 27% lower. When the cement capacity was less than 530 million tons per year, the additional cost of cement production was 95-300 yuan·t-1. Under technological progress to 2030, the levelized cost will be reduced by 9%-15%. The regions with early demonstration advantages of full-chain CO2-enhanced water recovery technology were Xinjiang, Inner Mongolia, Ningxia, Henan, and Hebei. Additionally, the areas suitable for cement CCUS cluster included Ordos Basin, Junggar Basin, Bohai Bay Basin, and Songliao Basin. It is technically feasible for the cement industry to deploy full-chain CCUS projects, and low-cost projects have an early demonstration opportunity. These results can provide a quantitative reference for the low-carbon development of the cement industry and the commercial deployment of CCUS in cement production.

15.
Cell ; 186(23): 5028-5040.e14, 2023 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-37852257

RESUMO

Wnt proteins are enzymatically lipidated by Porcupine (PORCN) in the ER and bind to Wntless (WLS) for intracellular transport and secretion. Mechanisms governing the transfer of these low-solubility Wnts from the ER to the extracellular space remain unclear. Through structural and functional analyses of Wnt7a, a crucial Wnt involved in central nervous system angiogenesis and blood-brain barrier maintenance, we have elucidated the principles of Wnt biogenesis and Wnt7-specific signaling. The Wnt7a-WLS complex binds to calreticulin (CALR), revealing that CALR functions as a chaperone to facilitate Wnt transfer from PORCN to WLS during Wnt biogenesis. Our structures, functional analyses, and molecular dynamics simulations demonstrate that a phospholipid in the core of Wnt-bound WLS regulates the association and dissociation between Wnt and WLS, suggesting a lipid-mediated Wnt secretion mechanism. Finally, the structure of Wnt7a bound to RECK, a cell-surface Wnt7 co-receptor, reveals how RECKCC4 engages the N-terminal domain of Wnt7a to activate Wnt7-specific signaling.


Assuntos
Receptores Acoplados a Proteínas G , Proteínas Wnt , Via de Sinalização Wnt , Barreira Hematoencefálica/metabolismo , Ligação Proteica , Receptores Acoplados a Proteínas G/metabolismo , Humanos , Proteínas Wnt/química , Proteínas Wnt/metabolismo
16.
bioRxiv ; 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37781607

RESUMO

Endocytosis and lysosomal trafficking of cell surface receptors can be triggered by interaction with endogenous ligands. Therapeutic approaches such as LYTAC1,2 and KineTAC3, have taken advantage of this to target specific proteins for degradation by fusing modified native ligands to target binding proteins. While powerful, these approaches can be limited by possible competition with the endogenous ligand(s), the requirement in some cases for chemical modification that limits genetic encodability and can complicate manufacturing, and more generally, there may not be natural ligands which stimulate endocytosis through a given receptor. Here we describe general protein design approaches for designing endocytosis triggering binding proteins (EndoTags) that overcome these challenges. We present EndoTags for the IGF-2R, ASGPR, Sortillin, and Transferrin receptors, and show that fusing these tags to proteins which bind to soluble or transmembrane protein leads to lysosomal trafficking and target degradation; as these receptors have different tissue distributions, the different EndoTags could enable targeting of degradation to different tissues. The modularity and genetic encodability of EndoTags enables AND gate control for higher specificity targeted degradation, and the localized secretion of degraders from engineered cells. The tunability and modularity of our genetically encodable EndoTags should contribute to deciphering the relationship between receptor engagement and cellular trafficking, and they have considerable therapeutic potential as targeted degradation inducers, signaling activators for endocytosis-dependent pathways, and cellular uptake inducers for targeted antibody drug and RNA conjugates.

17.
Food Sci Nutr ; 11(10): 6106-6115, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37823123

RESUMO

Increasing findings devote to searching for natural active compositions as additives to ameliorate health status. Anthocyanin, water-soluble natural pigment, has been concerned due to its favorable antioxidant activity. In this study, we purified anthocyanin from Dioscorea alata L., identified its compounds, and evaluated its antioxidant properties. The results indicated that the purity of anthocyanin increased to 39.59 ± 1.56%, 60.18 ± 1.97%, and 81.08 ± 1.97% after purification via AB-8 macroporous resin, Sep-Pak C18 solid phase, and LH-20 Sephadex stepwise. Ultra-performance liquid chromatography tandem mass spectrometer results indicated that paeoniflorin-3,5-O-dihexoside, petunin-3-O-feruloyl-glucoside-5-O-glucoside, cyanidin-3-O-feruloyl glucoside-5-O-glucoside, cyanidin-3-O-sophoroside, and petunin-3,5-O-dihexoside were the major compounds. The purified anthocyanin exhibited stronger antioxidant activity than the unpurified extract and ascorbic acid, whereas weaker than that of cyanidin-3-O-glucoside in general, which was assessed using DPPH, ABTS, and Fe3+ reducing capacity methods. Moreover, the purified anthocyanin increased GSH-Px, total antioxidant capacity, and superoxide dismutase activities and decreased malondialdehyde concentration on serum in mice after administering lipopolysaccharide for 24 h (p < .05). To summarize, the purified anthocyanin boasts more outstanding antioxidant properties than that of crude extracts. These results provide a reference with source of anthocyanin and it is conducive to use Dioscorea alata L. resources.

18.
Opt Lett ; 48(20): 5213-5216, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37831830

RESUMO

In this Letter, we report the application of planar liquid crystal (LC) devices in axial focus shaping, proving that LC diffractive optical elements (DOEs) can achieve continuous adjustment of a symmetrical axial light field by changing the ellipticity of the incident light and can flexibly and quickly achieve various axial light field designs through an axial iterative Fourier transform algorithm. The LC DOE achieves a quasi-continuous phase and an extremely high transmittance (98.6% at 1030 nm), which makes the focusing efficiency of the LC DOE with two segments of uniform focal depths as high as 84%. The experimental results demonstrate the accurate optical field shaping effect and the axial intensity adjustable ability of LC DOE, indicating potential applications in optical tomography and precision manufacturing, among others.

19.
Trends Biochem Sci ; 48(10): 829-831, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37714138
20.
Nat Struct Mol Biol ; 30(11): 1746-1754, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37770716

RESUMO

The fusion of mononucleated myoblasts produces multinucleated muscle fibers leading to the formation of skeletal muscle. Myomaker, a skeletal muscle-specific membrane protein, is essential for myoblast fusion. Here we report the cryo-EM structures of mouse Myomaker (mMymk) and Ciona robusta Myomaker (cMymk). Myomaker contains seven transmembrane helices (TMs) that adopt a G-protein-coupled receptor-like fold. TMs 2-4 form a dimeric interface, while TMs 3 and 5-7 create a lipid-binding site that holds the polar head of a phospholipid and allows the alkyl tails to insert into Myomaker. The similarity of cMymk and mMymk suggests a conserved Myomaker-mediated cell fusion mechanism across evolutionarily distant species. Functional analyses demonstrate the essentiality of the dimeric interface and the lipid-binding site for fusogenic activity, and heterologous cell-cell fusion assays show the importance of transcellular interactions of Myomaker protomers for myoblast fusion. Together, our findings provide structural and functional insights into the process of myoblast fusion.


Assuntos
Músculo Esquelético , Mioblastos , Animais , Camundongos , Microscopia Crioeletrônica , Diferenciação Celular , Músculo Esquelético/metabolismo , Mioblastos/metabolismo , Lipídeos , Desenvolvimento Muscular/fisiologia
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