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1.
Am J Pathol ; 194(5): 796-809, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38395146

RESUMO

α-Synuclein (α-Syn) is a key determinator of Parkinson disease (PD) pathology, but synapse and microcircuit pathologies in the retina underlying visual dysfunction are poorly understood. Herein, histochemical and ultrastructural analyses and ophthalmologic measurements in old transgenic M83 PD model (mice aged 16 to 18 months) indicated that abnormal α-Syn aggregation in the outer plexiform layer (OPL) was associated with degeneration in the C-terminal binding protein 2 (CtBP2)+ ribbon synapses of photoreceptor terminals and protein kinase C alpha (PKCα)+ rod bipolar cell terminals, whereas α-Syn aggregates in the inner retina correlated with the reduction and degeneration of tyrosine hydroxylase- and parvalbumin-positive amacrine cells. Phosphorylated Ser129 α-synuclein expression was strikingly restricted in the OPL, with the most severe degenerations in the entire retina, including mitochondrial degeneration and loss of ribbon synapses in 16- to 18-month-old mice. These synapse- and microcircuit-specific deficits of the rod pathway at the CtBP2+ rod terminals and PKCα+ rod bipolar and amacrine cells were associated with attenuated a- and b-wave amplitudes and oscillatory potentials on the electroretinogram. They were also associated with the impairment of visual functions, including reduced contrast sensitivity and impairment of the middle range of spatial frequencies. Collectively, these findings demonstrate that α-Syn aggregates cause the synapse- and microcircuit-specific deficits of the rod pathway and the most severe damage to the OPL, providing the retinal synaptic and microcircuit basis for visual dysfunctions in PD.


Assuntos
Proteína Quinase C-alfa , alfa-Sinucleína , Animais , Camundongos , alfa-Sinucleína/metabolismo , Células Amácrinas/metabolismo , Proteína Quinase C-alfa/metabolismo , Retina/metabolismo , Células Fotorreceptoras Retinianas Bastonetes/metabolismo , Células Fotorreceptoras Retinianas Bastonetes/ultraestrutura , Sinapses/metabolismo , Fatores de Transcrição/metabolismo
2.
Blood ; 141(21): 2629-2641, 2023 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-36867840

RESUMO

The communication of talin-activated integrin αIIbß3 with the cytoskeleton (integrin outside-in signaling) is essential for platelet aggregation, wound healing, and hemostasis. Filamin, a large actin crosslinker and integrin binding partner critical for cell spreading and migration, is implicated as a key regulator of integrin outside-in signaling. However, the current dogma is that filamin, which stabilizes inactive αIIbß3, is displaced from αIIbß3 by talin to promote the integrin activation (inside-out signaling), and how filamin further functions remains unresolved. Here, we show that while associating with the inactive αIIbß3, filamin also associates with the talin-bound active αIIbß3 to mediate platelet spreading. Fluorescence resonance energy transfer-based analysis reveals that while associating with both αIIb and ß3 cytoplasmic tails (CTs) to maintain the inactive αIIbß3, filamin is spatiotemporally rearranged to associate with αIIb CT alone on activated αIIbß3. Consistently, confocal cell imaging indicates that integrin α CT-linked filamin gradually delocalizes from the ß CT-linked focal adhesion marker-vinculin likely because of the separation of integrin α/ß CTs occurring during integrin activation. High-resolution crystal and nuclear magnetic resonance structure determinations unravel that the activated integrin αIIb CT binds to filamin via a striking α-helix→ß-strand transition with a strengthened affinity that is dependent on the integrin-activating membrane environment containing enriched phosphatidylinositol 4,5-bisphosphate. These data suggest a novel integrin αIIb CT-filamin-actin linkage that promotes integrin outside-in signaling. Consistently, disruption of such linkage impairs the activation state of αIIbß3, phosphorylation of focal adhesion kinase/proto-oncogene tyrosine kinase Src, and cell migration. Together, our findings advance the fundamental understanding of integrin outside-in signaling with broad implications in blood physiology and pathology.


Assuntos
Complexo Glicoproteico GPIIb-IIIa de Plaquetas , Glicoproteína IIb da Membrana de Plaquetas , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Glicoproteína IIb da Membrana de Plaquetas/metabolismo , Actinas/metabolismo , Filaminas/metabolismo , Talina/metabolismo , Plaquetas/metabolismo
3.
Prostate ; 84(11): 1033-1046, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38708958

RESUMO

BACKGROUND: Preclinical models recapitulating the metastatic phenotypes are essential for developing the next-generation therapies for metastatic prostate cancer (mPC). We aimed to establish a cohort of clinically relevant mPC models, particularly androgen receptor positive (AR+) bone metastasis models, from LuCaP patient-derived xenografts (PDX) that reflect the heterogeneity and complexity of mPC. METHODS: PDX tumors were dissociated into single cells, modified to express luciferase, and were inoculated into NSG mice via intracardiac injection. The progression of metastases was monitored by bioluminescent imaging. Histological phenotypes of metastases were characterized by immunohistochemistry and immunofluorescence staining. Castration responses were further investigated in two AR-positive models. RESULTS: Our PDX-derived metastasis (PDM) model collection comprises three AR+ adenocarcinomas (ARPC) and one AR- neuroendocrine carcinoma (NEPC). All ARPC models developed bone metastases with either an osteoblastic, osteolytic, or mixed phenotype, while the NEPC model mainly developed brain metastasis. Different mechanisms of castration resistance were observed in two AR+ PDM models with distinct genotypes, such as combined loss of TP53 and RB1 in one model and expression of AR splice variant 7 (AR-V7) expression in another model. Intriguingly, the castration-resistant tumors displayed inter- and intra-tumor as well as organ-specific heterogeneity in lineage specification. CONCLUSION: Genetically diverse PDM models provide a clinically relevant system for biomarker identification and personalized medicine in metastatic castration-resistant prostate cancer.


Assuntos
Neoplasias Ósseas , Modelos Animais de Doenças , Neoplasias da Próstata , Receptores Androgênicos , Masculino , Neoplasias Ósseas/secundário , Neoplasias Ósseas/metabolismo , Animais , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Humanos , Camundongos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/genética , Adenocarcinoma/patologia , Adenocarcinoma/secundário , Adenocarcinoma/metabolismo , Adenocarcinoma/genética , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/genética , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/metabolismo , Carcinoma Neuroendócrino/genética
4.
Anal Chem ; 96(15): 6045-6054, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38569073

RESUMO

Plastic pollution pervades natural environments and wildlife. Consequently, high-throughput detection methods for plastic debris are urgently needed. A novel method was developed to detect plastic debris larger than 0.5 mm, which integrated an extraction method with low organic loss and plastic damage alongside a classification method for fused images. This extraction method broadened the size range of the remaining plastic debris, while the fusion solved the low spatial resolution of hyperspectral images and the absence of spectral information in red-green-blue (RGB) images. This method was validated for plastic debris in digestate, compost, and sludge, with extraction demonstrating 100% recovery rates for all samples. After fusion, the spatial resolution of hyperspectral images was improved about five times. Classification recall for the fused hyperspectral images achieved 97 ± 8%, surpassing 83 ± 29% of the raw images. Application of this method to solid digestate detected 1030 ± 212 items/kg of plastic debris, comparable with the conventional Fourier transform infrared spectroscopic result of 1100 ± 436 items/kg. This developed method can investigate plastic debris in complex matrices, simultaneously addressing a wide range of sizes and types. This capability helps acquire reliable data to predict secondary microplastic generation and conduct a risk assessment.

5.
Small ; : e2400770, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38934533

RESUMO

Increased expression of immune check point genes, such as PD-L1, is one of the main reasons for immunosuppression, especially for colon cancer. Development of novel therapeutic strategies is of great importance to improve the prognosis. In this study, outer membrane vesicles (OMV) derived from Gram-negative bacteria are engineered to immune checkpoint blockade nanosystem for efficient elicitation of anti-tumor immunity. Briefly, the OMVs are engineered with Lyp1-Traptavidin (S52G, R53D mutant of streptavidin) fusion protein displayed on the surface. The Lyp-1 endows the OMV with the capacity to target tumor tissues, while the Traptavidin ensures easy decoration of biotinylated anti-PD-L1 and biotinylated M6P (mannose 6-phosphate). The simultaneously anchored anti-PD-L1 and M6P (ligand for cation-independent mannose 6-phosphate receptor) on the engineered OMVs coordinately direct the membrane PD-L1 to lysosome for degradation, and thus unleash the anti-tumor immunity. With syngeneic tumor model, the engineered OMVs are confirmed to boost immunity, inhibit cancer growth, and thus prolong survival. Together, A proposed OMV-based modular nanosystem that enables assembly of biotinylated anti-PD-L1 and M6P on the surface for tumor-targeted immune checkpoint blockade.

6.
Brief Bioinform ; 23(1)2022 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-34864871

RESUMO

Advances in high-throughput experimental technologies promote the accumulation of vast number of biomedical data. Biomedical link prediction and single-cell RNA-sequencing (scRNA-seq) data imputation are two essential tasks in biomedical data analyses, which can facilitate various downstream studies and gain insights into the mechanisms of complex diseases. Both tasks can be transformed into matrix completion problems. For a variety of matrix completion tasks, matrix factorization has shown promising performance. However, the sparseness and high dimensionality of biomedical networks and scRNA-seq data have raised new challenges. To resolve these issues, various matrix factorization methods have emerged recently. In this paper, we present a comprehensive review on such matrix factorization methods and their usage in biomedical link prediction and scRNA-seq data imputation. Moreover, we select representative matrix factorization methods and conduct a systematic empirical comparison on 15 real data sets to evaluate their performance under different scenarios. By summarizing the experimental results, we provide general guidelines for selecting matrix factorization methods for different biomedical matrix completion tasks and point out some future directions to further improve the performance for biomedical link prediction and scRNA-seq data imputation.


Assuntos
Análise de Dados , Análise de Célula Única , Análise de Sequência de RNA/métodos , Análise de Célula Única/métodos , Sequenciamento do Exoma
7.
J Transl Med ; 22(1): 286, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38493143

RESUMO

BACKGROUND: Osteoarthritis (OA) is a degenerative disease characterized by chronic inflammation of the joint. As the disease progresses, patients will gradually develop symptoms such as pain, physical limitations and even disability. The risk factors for OA include genetics, gender, trauma, obesity, and age. Unfortunately, due to limited understanding of its pathological mechanism, there are currently no effective drugs or treatments to suspend the progression of osteoarthritis. In recent years, some studies found that low-intensity pulsed ultrasound (LIPUS) may have a positive effect on osteoarthritis. Nonetheless, the exact mechanism by which LIPUS affects osteoarthritis remains unknown. It is valuable to explore the specific mechanism of LIPUS in the treatment of OA. METHODS: In this study, we validated the potential therapeutic effect of LIPUS on osteoarthritis by regulating the YAP-RIPK1-NF-κB axis at both cellular and animal levels. To verify the effect of YAP on OA, the expression of YAP was knocked down or overexpressed by siRNA and plasmid in chondrocytes and adeno-associated virus was injected into the knee joint of rats. The effect of LIPUS was investigated in inflammation chondrocytes induced by IL-1ß and in the post-traumatic OA model. RESULTS: In this study, we observed that YAP plays an important role in the development of osteoarthritis and knocking down of YAP significantly inhibited the inflammation and alleviated cartilage degeneration. We also demonstrated that the expression of YAP was increased in osteoarthritis chondrocytes and YAP could interact with RIPK1, thereby regulating the NF-κB signal pathway and influencing inflammation. Moreover, we also discovered that LIPUS decreased the expression of YAP by restoring the impaired autophagy capacity and inhibiting the binding between YAP and RIPK1, thereby delaying the progression of osteoarthritis. Animal experiment showed that LIPUS could inhibit cartilage degeneration and alleviate the progression of OA. CONCLUSIONS: These results showed that LIPUS is effective in inhibiting inflammation and cartilage degeneration and alleviate the progression of OA. As a result, our results provide new insight of mechanism by which LIPUS delays the development of osteoarthritis, offering a novel therapeutic regimen for osteoarthritis.


Assuntos
NF-kappa B , Osteoartrite , Humanos , Ratos , Animais , NF-kappa B/metabolismo , Osteoartrite/terapia , Osteoartrite/patologia , Ondas Ultrassônicas , Inflamação/patologia , Autofagia , Condrócitos , Interleucina-1beta/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo
8.
Environ Sci Technol ; 58(15): 6659-6669, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38557040

RESUMO

Revealing the role of functional redundancy is of great importance considering its key role in maintaining the stability of microbial ecosystems in response to various disturbances. However, experimental evidence on this point is still lacking due to the difficulty in "manipulating" and depicting the degree of redundancy. In this study, manipulative experiments of functional redundancy were conducted by adopting the mixed inoculation strategy to evaluate its role in engineered anaerobic digestion systems under ammonium inhibition conditions. The results indicated that the functional redundancy gradient was successfully constructed and confirmed by evidence from pathway levels. All mixed inoculation groups exhibited higher methane production regardless of the ammonium level, indicating that functional redundancy is crucial in maintaining the system's efficiency. Further analysis of the metagenome-assembled genomes within different functional guilds revealed that the extent of redundancy decreased along the direction of the anaerobic digestion flow, and the role of functional redundancy appeared to be related to the stress level. The study also found that microbial diversity of key functional populations might play a more important role than their abundance on the system's performance under stress. The findings provide direct evidence and highlight the critical role of functional redundancy in enhancing the efficiency and stability of anaerobic digestion.


Assuntos
Compostos de Amônio , Microbiota , Anaerobiose , Reatores Biológicos , Metagenoma , Metano
9.
Environ Sci Technol ; 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38905014

RESUMO

A regular tetrahedron model was established to pierce the fractionation of dissolved organic matter (DOM) among quaternary components by using high-resolution mass spectrometry. The model can stereoscopically visualize molecular formulas of DOM to show the preference to each component according to the position in a regular tetrahedron. A classification method was subsequently developed to divide molecular formulas into 15 categories related to fractionation ratios, the relative change of which was demonstrated to be convergent with the uncertainty of mass peak area. The practicality of the regular tetrahedron model was verified by seven kinds of sludge from waste leachate treatment and sewage wastewater treatment plants by using stratification of extracellular polymeric substances coupled with Orbitrap MS as an example, presenting the DOM chemodiversity in stratified sludge flocs. Sensitivity analysis proved that classification results were relatively stable with the perturbation of four model parameters. Multinomial logistic regression analysis could further help identify the effect of molecular properties on the fractionation of DOM based on the classification results of the regular tetrahedron model. This model offers a methodology for the assessment of specificity of sequential extraction on DOM from solid or semisolid components and simplifies the complex mathematical expression of fractionation coefficients for quaternary components.

10.
Environ Res ; 246: 118139, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38191048

RESUMO

With the implementation of municipal solid waste source segregation, the enormous sorted biogenic waste has become an issue that needs to be seriously considered. Anaerobic digestion, which can produce biogas and extract floating oil for biodiesel production, is the most prevalent treatment in China for waste management and greenhouse gas (GHG) emissions reduction, in accordance with Sustainable Development Goal 13 of the United Nations. Herein, a large-scale biogas plant with a capacity of 1000 tonnes of biogenic waste (400 tonnes of restaurant biogenic waste and 600 tonnes of kitchen biogenic waste) per day was investigated onsite using material flow analysis, and the parts of the biogas plant were thoroughly analyzed, especially the pretreatment system for biogenic waste impurity removal and homogenization. The results indicated that the loss of the total biodegradable organic matter was 41.8% (w/w) of daily feedstock and the loss of biogas potential was 18.8% (v/v) of daily feedstock. Life cycle assessment revealed that the 100-year GHG emissions were -61.2 kgCO2-eq per tonne biogenic waste. According to the sensitivity analysis, pretreatment efficiency, including biodegradable organic matter recovery and floating oil extraction, considerably affected carbon reduction potential. However, when the pretreatment efficiency deteriorated, GHG benefits of waste source segregation and the subsequent biogenic waste anaerobic digestion would be reduced.


Assuntos
Gases de Efeito Estufa , Eliminação de Resíduos , Gerenciamento de Resíduos , Biocombustíveis , Efeito Estufa , Anaerobiose , Carbono , Gerenciamento de Resíduos/métodos , Resíduos Sólidos , Eliminação de Resíduos/métodos
11.
Artigo em Inglês | MEDLINE | ID: mdl-38401076

RESUMO

Objective: This study aims to assess the efficacy of laparoscopic modified uterine incision pressure repair in treating type II-III cesarean scar pregnancy (CSP). Methods: A total of 20 patients diagnosed with type II-III CSP and admitted to the Affiliated Hospital of Guizhou Medical University between April 2021 and May 2023 were enrolled. The patients were divided into two groups: the study group (Group A), consisting of newly treated surgical patients, and the control group (Group B), including patients with type II-III CSP treated by doctors of similar grade and surgical experience (non-novel). Various parameters, including age, menopause duration, pregnancy and delivery history, cesarean section frequency, preoperative human chorionic gonadotropin (HCG) levels, pregnancy sac size, HCG turnover time, operation duration, intraoperative blood loss, blood transfusion requirements, and hospitalization costs, were compared. Results: When comparing mean age, menopause duration, preoperative HCG levels, pregnancy and cesarean section frequencies, pregnancy sac size, and HCG turnover time, no statistically significant differences were observed (P > .05). The number of transfusions and hospitalization costs in Group A were lower than in Group B, although the differences were not statistically significant (P > .05). However, operative time, intraoperative bleeding, and hospitalization costs were significantly lower in Group A compared to Group B (P < .05). Conclusions: The laparoscopic modified uterine incision pressure repair method demonstrated clinical value with its advantages of short operation time, reduced bleeding, lower costs, and rapid recovery for type II-III CSP.

12.
Arch Gynecol Obstet ; 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38194093

RESUMO

PURPOSE: Epidemiological studies examining the association between circulating micronutrients and the risk of hypertensive disorders during pregnancy (HDP) have produced inconsistent results. Therefore, we conducted a Mendelian randomization (MR) analysis to evaluate the potential causal relationship between micronutrients and HDP. METHODS: Nine micronutrients (beta-carotene, vitamin B6, vitamin B12, calcium, zinc, selenium, copper, folate, and phosphorus) were selected as the exposure factors. Summary data for gestational hypertension (14,727 cases and 196,143 controls) and preeclampsia/eclampsia (7212 cases and 174,266 controls) were extracted from the FinnGen consortium. The MR analysis employed the inverse variance weighted method and conducted a range of sensitivity analyses. RESULTS: The inverse variance weighted method indicated no significant causal relationship between nine genetically predicted micronutrient concentrations and gestational hypertension, as well as preeclampsia/eclampsia. Sensitivity analyses suggested the absence of pleiotropy. CONCLUSION: There is no strong evidence to support the causation between circulating micronutrients and hypertensive disorder during pregnancy.

13.
Aesthetic Plast Surg ; 48(7): 1298-1305, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38168822

RESUMO

BACKGROUND: Age-related blepharoptosis, or ptosis, affects vision and appearance. Associations with age, gender, BMI, and diabetes have been explored, but the link to blood lipids remains unclear. The impact on refraction also lacks consensus. This study addresses gaps by investigating ptosis prevalence and factors in a representative Chinese population, aiming for a comprehensive understanding. METHODS: A cross-sectional study was conducted among individuals aged 50 and above who were willing to participate in comprehensive systemic check-ups, behavioral questionnaires, and ophthalmic examinations at Yaoxi Community Health Center in Wenzhou City, Zhejiang Province. RESULTS: The prevalence of blepharoptosis among the elderly participants at this health center was 27.16%. Individuals with blepharoptosis tended to be older, male, exhibited slightly higher body mass index, wider waist circumference, engaged in lower exercise frequency, and had a higher prevalence of hypertension, diabetes, and with-the-rule astigmatism compared to their counterparts without these conditions. Adjusting for all other confounding variables, older age, being male, higher fasting plasma glucose (FPG), and lower exercise frequency displayed statistically significant relationships with blepharoptosis. After examining the distribution of blepharoptosis degrees within relevant factor subgroups, we noted a higher prevalence of severe ptosis in subgroups associated with older age, male gender, higher FPG, and against-the-rule astigmatism. CONCLUSION: The notable associations with age, gender, FPG, and exercise level suggest a multifactorial etiology for blepharoptosis. The observed link between with-the-rule astigmatism and blepharoptosis implies a potential contributory role in the refractive aspect of blepharoptosis. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Assuntos
Povo Asiático , Blefaroptose , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Etários , Povo Asiático/estatística & dados numéricos , Blefaroptose/epidemiologia , China/epidemiologia , Estudos Transversais , Prevalência , Medição de Risco , Fatores de Risco
14.
J Environ Sci (China) ; 139: 483-495, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38105071

RESUMO

The significant increase in the demand for biomass waste treatment after garbage classification has led to housefly larvae treatment becoming an attractive treatment option. It can provide a source of protein while treating biomass waste, which means that nutrients can be returned to the natural food chain. However, the performance of this technology in terms of its environmental impacts is still unclear, particularly with regards to global warming potential (GWP).This study used a life cycle assessment (LCA) approach to assess a housefly larvae treatment plant with a treatment capacity of 50 tons of biomass waste per day. The LCA results showed that the 95% confidence intervals for the GWP in summer and winter were determined to be 24.46-32.81 kg CO2 equivalent (CO2-eq)/ton biomass waste and 5.37-10.08 kg CO2-eq/ton biomass waste, respectively. The greater GWP value in summer is due to the longer ventilation time and higher ventilation intensity in summer, which consumes more power. The main GWP contributions are from (1) electricity needs (accounting for 78.6% of emissions in summer and 70.2% in winter) and (2) product substitution by mature housefly larvae and compost (both summer and winter accounting for 96.8% of carbon reduction).


Assuntos
Compostagem , Moscas Domésticas , Animais , Aquecimento Global , Larva , Dióxido de Carbono
15.
J Biol Chem ; 298(3): 101710, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35150743

RESUMO

Coronavirus disease 2019 (COVID-19) is a highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is broadly accepted that SARS-CoV-2 utilizes its spike protein to recognize the extracellular domain of angiotensin-converting enzyme 2 (ACE2) to enter cells for viral infection. However, other mechanisms of SARS-CoV-2 cell entry may occur. We show quantitatively that the SARS-CoV-2 spike protein also binds to the extracellular domain of broadly expressed integrin α5ß1 with an affinity comparable to that of SARS-CoV-2 binding to ACE2. More importantly, we provide direct evidence that such binding promotes the internalization of SARS-CoV-2 into non-ACE2 cells in a manner critically dependent upon the activation of the integrin. Our data demonstrate an alternative pathway for the cell entry of SARS-CoV-2, suggesting that upon initial ACE2-mediated invasion of the virus in the respiratory system, which is known to trigger an immune response and secretion of cytokines to activate integrin, the integrin-mediated cell invasion of SARS-CoV-2 into the respiratory system and other organs becomes effective, thereby promoting further infection and progression of COVID-19.


Assuntos
COVID-19 , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Internalização do Vírus , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/metabolismo , COVID-19/virologia , Humanos , Integrinas/metabolismo , Ligação Proteica , SARS-CoV-2/metabolismo , SARS-CoV-2/fisiologia , Glicoproteína da Espícula de Coronavírus/metabolismo
16.
Anal Chem ; 95(9): 4412-4420, 2023 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-36820858

RESUMO

Insights into carbon sources (biogenic and fossil carbon) and contents in solid waste are vital for estimating the carbon emissions from incineration plants. However, the traditional methods are time-, labor-, and cost-intensive. Herein, high-quality data sets were established after analyzing the carbon contents and infrared spectra of substantial samples using elemental analysis and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), respectively. Then, five classification and eight regression machine learning (ML) models were evaluated to recognize the proportion of biogenic and fossil carbon in solid waste. Using the optimized data preprocessing approach, the random forest (RF) classifier with hyperparameter tuning ranked first in classifying the carbon group with a test accuracy of 0.969, and the carbon contents were successfully predicted by the RF regressor with R2 = 0.926 considering performance-interpretability-computation time competition. The above proposed algorithms were further validated with real environmental samples, which exhibited robust performance with an accuracy of 0.898 for carbon group classification and an R2 value of 0.851 for carbon content prediction. The reliable results indicate that ATR-FTIR coupled with ML algorithms is feasible for rapidly identifying both carbon groups and content, facilitating the calculation and assessment of carbon emissions from solid waste incineration.

17.
Environ Sci Technol ; 57(42): 16033-16042, 2023 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-37822265

RESUMO

Halogenated organic compounds in wastewater are persistent and bioaccumulative contaminants of great concern, but few are known at the molecular level. Herein, we focus on nontarget screening of halogenated dissolved organic matter (DOM) in highly concentrated organic matrices of waste leachates and their concentrates. Solid-phase extraction (SPE) was optimized before capturing halogenated signatures via HaloSeeker 2.0 software on mining full-scan high-resolution mass spectrometry (HRMS) fingerprints. This study identified 438 Cl-/Br-containing DOM formulas in 21 leachates and membrane concentrates. Among them, 334 formulas were achieved via SPE with mixed-sorbent cartridges (mixed-SPE), surpassing the 164 formulas achieved through Bond Elut PPL cartridges (PPL-SPE). Herein, only four samples identified via PPL-SPE exhibited a resolution of >50% for extracted Cl-/Br-containing DOM by either SPE. The halogenated DOM constituted 6.87% of the total DOM mass features. Nevertheless, more abundant adsorbable organic halogens deciphered waste leachates and highly concentrated waste streams as reservoirs for halogenated contaminants. Remarkably, 75.7-98.1% of Cl-/Br-containing DOM in primary membrane concentrates remained stable through the secondary membrane treatment, indicating the persistence of these unknown contaminants even post-treatment.


Assuntos
Matéria Orgânica Dissolvida , Compostos Orgânicos , Espectrometria de Massas , Compostos Orgânicos/análise , Águas Residuárias , Extração em Fase Sólida/métodos
18.
Environ Res ; 238(Pt 1): 117072, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37690627

RESUMO

Powdered activated carbon (PAC) adsorption is regarded as an efficient method for removing odorants from drinking water. However, in eutrophic aquatic environments, the presence of algal organic matter (AOM) produced by cyanobacteria considerably impedes the adsorption of odorous compounds by activated carbon. This study focused on investigating the adsorption characteristics of three representative odorants: 2-methylisoborneol (2-MIB), ß-cyclocitral (ß-cyclo), and butyl sulfide (BS) by PAC and the effects of AOM on the PAC adsorption of odorants. The removal of the three odorants reached 83.5-97.5% at a PAC dosage of 10 mg/L after 12 h of exposure in a competition-free scenario. The adsorption kinetics demonstrated higher conformity (R2 > 0.9) with the pseudo-second-order model, whereas the adsorption capacity exhibited stronger conformity (R2 > 0.9) with the Freundlich model. The presence of AOM resulted in varying levels of competition for PAC for the adsorption of the three odorants. As the concentration of AOM increased from 0 to 5 mg C/L, the removal of 2-MIB was the most affected (from 83.5% to 10.0%), followed by ß-cyclo (from 86.6% to 55.0%), and BS (from 97.5% to 92.0%). The competitive adsorption of AOM at the molecular level was studied using density functional theory (DFT). The DFT results suggested that odorants with higher and more uniformly distributed electrostatic potentials exhibited a heightened affinity for PAC adsorption and a diminished susceptibility to disruption caused by AOM. This study provides valuable insights into the mitigation of odorous compounds during drinking water purification.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Adsorção , Carvão Vegetal , Odorantes , Purificação da Água/métodos
19.
Ophthalmic Res ; 66(1): 940-948, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37062276

RESUMO

INTRODUCTION: The aim of this study was to compare the patterns of visual field (VF) defects in primary angle-closure glaucoma (PACG) to control groups of eyes with high-tension glaucoma (HTG) and normal-tension glaucoma (NTG). METHODS: Forty-eight eyes with PACG were enrolled, and control eyes with HTG and NTG matched for age, sex, and mean deviation of VF defect were selected. VF tests were performed using the 24-2 program of the Humphrey field analyzer. VF defects were classified into six patterns with the Ocular Hypertension Treatment Study classification system and were categorized into three stages (early, moderate, and advanced). Each hemifield was divided into five regions according to the Glaucoma Hemifield Test (GHT). The mean total deviation (TD) of each GHT region was calculated. RESULTS: Compared with HTG and NTG groups, the partial arcuate VF defects were more common in the PACG group. In the PACG group, the nasal GHT region in the inferior hemifield had the worst mean TD (-8.48 ± 8.62 dB), followed by the arcuate 1 (-7.81 ± 7.91 dB), arcuate 2 (-7.46 ± 7.43 dB), paracentral (-7.19 ± 7.98 dB), and central (-5.14 ± 6.24 dB) regions; the mean TD of the central region was significantly better than those for all other regions (all p < 0.05). A similar trend was observed in the superior hemifield in the PACG group but not the VF hemifields of the HTG and NTG groups. CONCLUSION: Patterns of VF defect in PACG patients differ from those with HTG and NTG. This discrepancy might be due to the differences in the pathogenic mechanisms of glaucomatous optic neuropathy.


Assuntos
Glaucoma de Ângulo Fechado , Glaucoma de Ângulo Aberto , Glaucoma , Glaucoma de Baixa Tensão , Humanos , Campos Visuais , Glaucoma de Ângulo Aberto/complicações , Glaucoma de Ângulo Aberto/diagnóstico , Glaucoma de Ângulo Aberto/patologia , Pressão Intraocular , Glaucoma/patologia , Glaucoma de Baixa Tensão/diagnóstico , Testes de Campo Visual , Transtornos da Visão , Células Ganglionares da Retina/patologia
20.
Med Teach ; : 1-8, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37910012

RESUMO

INTRODUCTION: Due to policy changes in the context of COVID-19 pandemic, online teaching has become the main form of class in many Chinese universities. Flipped classroom has been widely used in other disciplines, but there is a dearth of evidence available about the use in online teaching of emergency medicine. This study aimed to develop a flipped classroom for online emergency medicine teaching and evaluate its effectiveness by comparing it with traditional lecture-based online teaching. METHODS: A total of 62 clinical medical undergraduates from Jinan University participated in this study from September to December in 2022. An online flipped classroom approach was developed (FC group, n = 31). Traditional lecture-based online teaching was applied as a contrast (LBT group, n = 31). The undergraduates completed examinations and questionnaires at the end of the course. A course experience questionnaire and course examination score were used to evaluate the effectiveness of the flipped classroom approach. RESULTS: Regarding the five dimensions of the course experience questionnaire, the scores for good teaching (3.47 ± 0.50 vs. 2.34 ± 0.48, p < .001), appropriate assessment (3.31 ± 0.68 vs. 2.95 ± 0.71, p = .043) and generic skills (3.16 ± 0.60 vs. 2.72 ± 0.39, p < .001) were higher for the FC group than for the LBT group. There was no significant difference between the two groups in clear goals and standards, and appropriate workload. The undergraduates in the FC group showed significantly higher overall satisfaction than those in the LBT group (3.52 ± 0.1.03 vs. 2.87 ± 0.92, p = .012). The examination scores (77.936 ± 11.573 vs. 70.484 ± 7.434, p < .001), especially the scores for questions related to case analysis (33.032 ± 5.363 vs. 26.968 ± 7.657, p < .001), were significantly higher in the FC group than in the LBT group. CONCLUSIONS: The flipped classroom for online teaching was efficient in improving undergraduates' emergency medical academic performance and promoting the development of clinical case analysis ability. These findings provide an alternative flipped classroom approach for online teaching of emergency medicine.

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