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Conventional near-field acoustic holography based on compressive sensing either does not fully exploit the underlying block-sparse structures of the signal or suffers from a mismatch between the actual and predefined block structure due to the lack of prior information about block partitions, resulting in poor accuracy in sound field reconstruction. In this paper, a pattern-coupled Bayesian compressive sensing method is proposed for sparse reconstruction of sound fields. The proposed method establishes a hierarchical Gaussian-Gamma probability model with a pattern-coupled prior based on the equivalent source method, transforming the sound field reconstruction problem into recovering the sparse coefficient vector of the equivalent source strengths within the compressive sensing framework. A set of hyperparameters is introduced to control the sparsity of each element in the sparse coefficient vector of the equivalent source strengths, where the sparsity of each element is determined by both its own hyperparameters and those of its immediate neighbors. This approach enables the promotion of block sparse solutions and achieves better performance in solving for the sparse coefficient vector of the equivalent source strengths without prior information of block partitions. The effectiveness and superiority of the proposed method in reconstructing sound fields are verified by simulations and experiments.
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ABSTRACT: Facial grimacing is used to quantify spontaneous pain in mice and other mammals, but scoring relies on humans with different levels of proficiency. Here, we developed a cloud-based software platform called PainFace ( http://painface.net ) that uses machine learning to detect 4 facial action units of the mouse grimace scale (orbitals, nose, ears, whiskers) and score facial grimaces of black-coated C57BL/6 male and female mice on a 0 to 8 scale. Platform accuracy was validated in 2 different laboratories, with 3 conditions that evoke grimacing-laparotomy surgery, bilateral hindpaw injection of carrageenan, and intraplantar injection of formalin. PainFace can generate up to 1 grimace score per second from a standard 30 frames/s video, making it possible to quantify facial grimacing over time, and operates at a speed that scales with computing power. By analyzing the frequency distribution of grimace scores, we found that mice spent 7x more time in a "high grimace" state following laparotomy surgery relative to sham surgery controls. Our study shows that PainFace reproducibly quantifies facial grimaces indicative of nonevoked spontaneous pain and enables laboratories to standardize and scale-up facial grimace analyses.
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Expresión Facial , Ratones Endogámicos C57BL , Dimensión del Dolor , Programas Informáticos , Animales , Ratones , Femenino , Programas Informáticos/normas , Dimensión del Dolor/métodos , Dimensión del Dolor/normas , Masculino , Dolor/diagnósticoRESUMEN
The development of precise RNA-editing tools is essential for the advancement of RNA therapeutics. CRISPR (clustered regularly interspaced short palindromic repeats) PspCas13b is a programmable RNA nuclease predicted to offer superior specificity because of its 30-nucleotide spacer sequence. However, its design principles and its on-target, off-target and collateral activities remain poorly characterized. Here, we present single-base tiled screening and computational analyses that identify key design principles for potent and highly selective RNA recognition and cleavage in human cells. We show that the de novo design of spacers containing guanosine bases at precise positions can greatly enhance the catalytic activity of inefficient CRISPR RNAs (crRNAs). These validated design principles (integrated into an online tool, https://cas13target.azurewebsites.net/ ) can predict highly effective crRNAs with ~90% accuracy. Furthermore, the comprehensive spacer-target mutagenesis revealed that PspCas13b can tolerate only up to four mismatches and requires ~26-nucleotide base pairing with the target to activate its nuclease domains, highlighting its superior specificity compared to other RNA or DNA interference tools. On the basis of this targeting resolution, we predict an extremely low probability of PspCas13b having off-target effects on other cellular transcripts. Proteomic analysis validated this prediction and showed that, unlike other Cas13 orthologs, PspCas13b exhibits potent on-target activity and lacks collateral effects.
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Delayed neuropsychiatric sequelae (DNS) significantly impact the quality of life in patients following acute carbon monoxide poisoning (COP). This systematic review and meta-analysis aimed to assess the relationship between serum neuron-specific enolase (NSE) levels at admission and the risk of DNS in adults after acute COP. Relevant observational studies with longitudinal follow-up were identified through searches in PubMed, Embase, Web of Science, Wanfang, and China National Knowledge Infrastructure databases. The random-effects model was used to aggregate results, accounting for potential heterogeneity. Nine cohort studies, including 1501 patients, were analyzed, with 254 (16.9%) developing DNS during follow-up. The pooled data indicated that elevated serum NSE in the early phase was linked to a higher risk of subsequent DNS (odds ratio per 1 ng/mL increase in NSE: 1.10, 95% confidence interval: 1.06 to 1.15, P < 0.001). Moderate heterogeneity (I2 = 46%) among the studies was entirely attributed to one study with the longest follow-up duration (22.3 months; I2 = 0% after excluding this study). Subgroup analyses based on country, study design, sample size, age, sex, admission carboxyhemoglobin levels, DNS incidence, follow-up duration, and quality score yielded consistent results (P for subgroup differences all > 0.05). In summary, high serum NSE levels in the early phase of acute COP are associated with an increased risk of developing DNS during follow-up.
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BACKGROUND & AIMS: New antiviral approaches that target multiple aspects of the HBV replication cycle to improve rates of functional cure are urgently required. HBV RNA represents a novel therapeutic target. Here, we programmed CRISPR-Cas13b endonuclease to specifically target the HBV pregenomic RNA and viral mRNAs in a novel approach to reduce HBV replication and protein expression. METHODS: Cas13b CRISPR RNAs (crRNAs) were designed to target multiple regions of HBV pregenomic RNA. Mammalian cells transfected with replication competent wild-type HBV DNA of different genotypes, a HBV-expressing stable cell line, a HBV infection model and a hepatitis B surface antigen (HBsAg)-expressing stable cell line were transfected with PspCas13b-BFP (blue fluorescent protein) and crRNA plasmids, and the impact on HBV replication and protein expression was measured. Wild-type HBV DNA, PspCas13b-BFP and crRNA plasmids were simultaneously hydrodynamically injected into mice, and serum HBsAg was measured. PspCas13b mRNA and crRNA were also delivered to a HBsAg-expressing stable cell line via lipid nanoparticles and the impact on secreted HBsAg determined. RESULTS: Our HBV-targeting crRNAs strongly suppressed HBV replication and protein expression in mammalian cells by up to 96% (p <0.0001). HBV protein expression was also reduced in a HBV-expressing stable cell line and in the HBV infection model. CRISPR-Cas13b crRNAs reduced HBsAg expression by 50% (p <0.0001) in vivo. Lipid nanoparticle-encapsulated PspCas13b mRNA reduced secreted HBsAg by 87% (p = 0.0168) in a HBsAg-expressing stable cell line. CONCLUSIONS: Together, these results show that CRISPR-Cas13b can be programmed to specifically target and degrade HBV RNAs to reduce HBV replication and protein expression, demonstrating its potential as a novel therapeutic option for chronic HBV infection. IMPACT AND IMPLICATIONS: Owing to the limitations of current antiviral therapies for hepatitis B, there is an urgent need for new treatments that target multiple aspects of the HBV replication cycle to improve rates of functional cure. Here, we present CRISPR-Cas13b as a novel strategy to target HBV replication and protein expression, paving the way for its development as a potential new treatment option for patients living with chronic hepatitis B.
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SLC26A2 is a vital solute carrier responsible for transporting essential nutritional ions, including sulfate, within the human body. Pathogenic mutations within SLC26A2 give rise to a spectrum of human diseases, ranging from lethal to mild symptoms. The molecular details regarding the versatile substrate-transporter interactions and the impact of pathogenic mutations on SLC26A2 transporter function remain unclear. Here, using cryo-electron microscopy, we determine three high-resolution structures of SLC26A2 in complexes with different substrates. These structures unveil valuable insights, including the distinct features of the homodimer assembly, the dynamic nature of substrate binding, and the potential ramifications of pathogenic mutations. This structural-functional information regarding SLC26A2 will advance our understanding of cellular sulfate transport mechanisms and provide foundations for future therapeutic development against various human diseases.
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Microscopía por Crioelectrón , Transportadores de Sulfato , Humanos , Transportadores de Sulfato/metabolismo , Transportadores de Sulfato/genética , Transportadores de Sulfato/química , Mutación , Unión Proteica , Modelos Moleculares , Sulfatos/metabolismo , Multimerización de Proteína , Células HEK293 , Sitios de UniónRESUMEN
BACKGROUND: In contemporary society, with the accelerated pace of work and life, more and more people feel different degrees of stress. Long-term stress may not only lead to insomnia, but also to mental health problems (e.g., anxiety and depression), which has a significant impact on people's quality of life and mental health. OBJECTIVE: This study primarily investigates the mechanism through which stress affects sleep quality among college students. METHODS: We conducted research on 1653 Chinese college students using four scales with high reliability and validity: stress, the Pittsburgh Sleep Quality Index, social anxiety, and rumination. RESULTS: The study found: (1) Stress can significantly and positively predict sleep quality and rumination; (2) Rumination can positively predict social anxiety; (3) Social anxiety can positively predict sleep quality; (4) Stress can affect sleep quality through social anxiety and rumination separately, and stress can also affect sleep quality through the chained mediation of rumination and social anxiety. CONCLUSION: This study reveals the relationship and mechanisms between stress and sleep quality. It not only deepens the research on the impact of stress on sleep quality but also provides theoretical support and new methods for mental health professionals to help clients improve their sleep quality. In practice, in addition to using some common psychological intervention methods to help individuals reduce stress, we should pay more attention to how to help clients reduce rumination and social anxiety, This is significant in improving the quality of an individual's sleep.
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The study measured the levels of azoxystrobin (AZ) and thiabendazole (TBZ) in wallboards and metabolite levels of these fungicides in children. The paper covering of wallboard samples contained a higher concentration of AZ and TBZ than the gypsum core, and similar amounts (w/w) of these two fungicides were present in the samples. These data suggest that commercial products containing a 1:1 (w/w) amount of AZ and TBZ, such as Sporgard® WB or Azo Tech™, were applied to the wallboard paper. This is the first detection of TBZ in mold-and-mildew resistant wallboards. The TBZ metabolite, 5OH-TBZ, was detected in 48% of urine samples collected from children aged 40-84 months, and was co-detected with AZ-acid, a common AZ metabolite, in 37.5% of the urine samples. The detection frequency of 5OH-TBZ was positively associated with the detection frequency of AZ-acid. These findings suggest that certain types of wallboards used in homes and commercial buildings may be a potential source of co-exposure to AZ and TBZ in humans.
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Recently, several ATP-binding cassette (ABC) importers have been found to adopt the typical fold of type IV ABC exporters. Presumably, these importers would function under the transport scheme of "alternating access" like those exporters, cycling through inward-open, occluded, and outward-open conformations. Understanding how the exporter-like importers move substrates in the opposite direction requires structural studies on all the major conformations. To shed light on this, here we report the structure of yersiniabactin importer YbtPQ from uropathogenic Escherichia coli in the occluded conformation trapped by ADP-vanadate (ADP-Vi) at a 3.1 Å resolution determined by cryo-electron microscopy. The structure shows unusual local rearrangements in multiple helices and loops in its transmembrane domains (TMDs). In addition, the dimerization of the nucleotide-binding domains (NBDs) promoted by the vanadate trapping is highlighted by the "screwdriver" action at one of the two hinge points. These structural observations are rare and thus provide valuable information to understand the structural plasticity of the exporter-like ABC importers.
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Transportadoras de Casetes de Unión a ATP , Vanadatos , Conformación Proteica , Transportadoras de Casetes de Unión a ATP/metabolismo , Microscopía por Crioelectrón , Modelos Moleculares , Adenosina TrifosfatoRESUMEN
Abstract Background In contemporary society, with the accelerated pace of work and life, more and more people feel different degrees of stress. Long-term stress may not only lead to insomnia, but also to mental health problems (e.g., anxiety and depression), which has a significant impact on people's quality of life and mental health. Objective This study primarily investigates the mechanism through which stress affects sleep quality among college students. Methods We conducted research on 1653 Chinese college students using four scales with high reliability and validity: stress, the Pittsburgh Sleep Quality Index, social anxiety, and rumination. Results The study found: (1) Stress can significantly and positively predict sleep quality and rumination; (2) Rumination can positively predict social anxiety; (3) Social anxiety can positively predict sleep quality; (4) Stress can affect sleep quality through social anxiety and rumination separately, and stress can also affect sleep quality through the chained mediation of rumination and social anxiety. Conclusion This study reveals the relationship and mechanisms between stress and sleep quality. It not only deepens the research on the impact of stress on sleep quality but also provides theoretical support and new methods for mental health professionals to help clients improve their sleep quality. In practice, in addition to using some common psychological intervention methods to help individuals reduce stress, we should pay more attention to how to help clients reduce rumination and social anxiety, This is significant in improving the quality of an individual's sleep.
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While environmental factors have been considered contributors to atherosclerosis, it remains unclear whether drinking water promotes foam cell formation, the initial event of atherosclerosis. This study revealed that drinking water from six major cities in China, namely, Harbin, Jinan, Shanghai, Wuhan, Chongqing, and Zhuhai, significantly promoted foam cell formation in an in vitro macrophage model at a minimum concentration fold of 2. Moreover, cholesterol efflux was significantly impeded by all samples at 2-16-fold, while cholesterol influx was induced only by samples from Jinan and Chongqing at 16-fold, suggesting the dominant role of efflux in foam cell formation. Interestingly, except for the sample from Jinan, the samples exhibited complete inhibition of liver X receptor α (LXRα) activities at 160-fold, indicating the potential role of chemicals in drinking water in promoting foam cell formation by antagonizing LXRα. Through LXRα protein affinity selection-mass spectrometry, we identified ten LXRα-binding compounds, with efavirenz being revealed for the first time as a significant inducer of foam cell formation through LXRα antagonism. Overall, this study clarifies the atherosclerotic risks posed by drinking water and demonstrates the efavirenz-related atherosclerotic effects.
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Aterosclerosis , Agua Potable , Receptores X del Hígado , Humanos , Aterosclerosis/inducido químicamente , Aterosclerosis/metabolismo , China , Colesterol/metabolismo , Ciudades , Receptores X del Hígado/antagonistas & inhibidoresRESUMEN
The expression of defensive responses to alerting sensory cues requires both general arousal and a specific arousal state associated with defensive emotions. However, it remains unclear whether these two forms of arousal can be regulated by common brain regions. We discovered that the medial sector of the auditory thalamus (ATm) in mice is a thalamic hub controlling both general and defensive arousal. The spontaneous activity of VGluT2-expressing ATm (ATmVGluT2+) neurons was correlated with and causally contributed to wakefulness. In sleeping mice, sustained ATmVGluT2+ population responses were predictive of sensory-induced arousal, the likelihood of which was markedly decreased by inhibiting ATmVGluT2+ neurons or multiple downstream pathways. In awake mice, ATmVGluT2+ activation led to heightened arousal accompanied by excessive anxiety and avoidance behavior. Notably, blocking their neurotransmission abolished alerting stimuli-induced defensive behaviors. These findings may shed light on the comorbidity of sleep disturbances and abnormal sensory sensitivity in specific brain disorders.
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Nivel de Alerta , Tálamo , Ratones , Animales , Nivel de Alerta/fisiología , Tálamo/fisiología , Vigilia/fisiología , Neuronas/fisiología , Transmisión SinápticaRESUMEN
The rubber antioxidant 6PPD has gained significant attention due to its highly toxic transformation product, 6PPD-quinone (6PPDQ). Despite their detection in urines of pregnant women, the placental transfer and developmental toxicity of 6PPD and 6PPDQ are unknown. Here, we treated C57Bl/6 mice with 4 mg/kg 6PPD or 6PPDQ to investigate their urine excretion and placental transfer. Female and male mice exhibited sex difference in excretion profiles of 6PPD and 6PPDQ. Urine concentrations of 6PPDQ were one order of magnitude lower than those of 6PPD, suggesting lower excretion and higher bioaccumulation of 6PPDQ. In pregnant mice treated with 6PPD or 6PPDQ from embryonic day 11.5 to 15.5, 6PPDQ showed â¼1.5-8 times higher concentrations than 6PPD in placenta, embryo body, and embryo brain, suggesting higher placental transfer of 6PPDQ. Using in vitro dual-luciferase reporter assays, we revealed that 6PPDQ activated the human retinoic acid receptor α (RARα) and retinoid X receptor α (RXRα) at concentrations as low as 0.3 µM, which was â¼10-fold higher than the concentrations detected in human urines. 6PPD activated the RXRα at concentrations as low as 1.2 µM. These results demonstrate the exposure risks of 6PPD and 6PPDQ during pregnancy and emphasize the need for further toxicological and epidemiological investigations.
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Benzoquinonas , Desarrollo Embrionario , Fenilendiaminas , Animales , Femenino , Humanos , Masculino , Ratones , Embarazo , Benzoquinonas/metabolismo , Benzoquinonas/toxicidad , Benzoquinonas/orina , Placenta/metabolismo , Fenilendiaminas/metabolismo , Fenilendiaminas/toxicidad , Fenilendiaminas/orina , Ratones Endogámicos C57BL , Distribución Tisular , Factores Sexuales , Desarrollo Embrionario/efectos de los fármacos , Células HEK293 , Receptor alfa de Ácido Retinoico/metabolismo , Receptor alfa X Retinoide/metabolismoRESUMEN
To solve the problem of sound field reconstruction with fewer measurement points, a sound field reconstruction method based on Bayesian compressive sensing is proposed. In this method, a sound field reconstruction model based on a combination of the equivalent source method and sparse Bayesian compressive sensing is established. The MacKay iteration of the relevant vector machine is used to infer the hyperparameters and estimate the maximum a posteriori probability of both the sound source strength and noise variance. The optimal solution for sparse coefficients with an equivalent sound source is determined to achieve the sparse reconstruction of the sound field. The numerical simulation results demonstrate that the proposed method has higher accuracy over the entire frequency range compared to the equivalent source method, indicating a better reconstruction performance and wider frequency applicability with undersampling. Moreover, in environments with low signal-to-noise ratios, the proposed method exhibits significantly lower reconstruction errors than the equivalent source method, indicating a superior anti-noise performance and greater robustness in sound field reconstruction. The experimental results further verify the superiority and reliability of the proposed method for sound field reconstruction with limited measurement points.
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Acústica , Modelos Teóricos , Teorema de Bayes , Reproducibilidad de los Resultados , SonidoRESUMEN
Wet keratin is a hallmark of adamantinomatous craniopharyngioma (ACP), which is frequently infiltrated by inflammatory cells. S100 calcium-binding protein A9 (S100A9) has been confirmed to play a decisive role in the development of inflammation. However, the relationship between wet keratin (keratin nodules) and S100A9 in ACP is poorly understood. The objective of the present study was to explore the expression of S100A9 in ACP and its association with wet keratin formation. Immunohistochemistry and immunofluorescence were used to detect the expression of S100A9, ß-catenin and Ki67 in 46 cases of ACP. A total of three online databases were used to analyze S100A9 gene expression and protein data. The results revealed that S100A9 was primarily expressed in wet keratin and some intratumoral and peritumoral cells, and its expression in wet keratin was upregulated in the high inflammation group (P=1.800x10-3). In addition, S100A9 was correlated with the degree of inflammation (r=0.6; P=7.412x10-3) and the percentage of Ki67-positive cells (r=0.37; P=1.000x10-2). In addition, a significant correlation was noted between the area of wet keratin and the degree of inflammation (r=0.51; P=2.500x10-4). In conclusion, the present study showed that S100A9 was upregulated in ACP and may be closely associated with wet keratin formation and the infiltration of inflammatory cells in ACP.
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BACKGROUND AND AIMS: Steatosis is the early pathological change in alcohol-associated liver disease. However, its precise mechanism is still unclear. The present study is aimed to explore the role and mechanism of acetyl-CoA synthetase 2 (ACSS2) in acute alcohol-induced lipogenesis. METHODS: The increase in ACSS2 nuclear import and histone H3 acetylation were observed in mice after intraperitoneally injected with 2 g/kg ethanol or oral administration of 5 g/kg ethanol and also validated in hepatocytes stimulated with ethanol or acetate. The role of ACSS2 was further explored in liver-specific ACSS2 knockdown mice fed with ethanol-containing diet. RESULTS: Alcohol challenge induced hepatic lipid deposition and upregulated lipogenic genes in mice. It also promoted ACSS2 nuclear import and increased histone H3 acetylation. In hepatocytes, ethanol induced similar phenomena whereas ACSS2 knockdown blocked histone acetylation and lipogenic gene induction. P300/CBP associated factor (PCAF), but not general control nonderepressible 5, CREB-binding protein (CBP) and p300, facilitated H3K9 acetylation responding to ethanol challenge. CUT&RUN assay showed the enrichment of acetylated histone H3K9 surrounding Fasn and Acaca promoters. These results indicated that ethanol metabolism promoted ACSS2 nuclear import to support lipogenesis via H3K9 acetylation. In alcohol-feeding mice, liver-specific ACSS2 knockdown blocked the interaction between PCAF and H3K9 and suppressed lipogenic gene induction in the liver, demonstrating the critical role of ACSS2 in lipogenesis. CONCLUSIONS: Our study demonstrated that alcohol metabolism generated acetyl-CoA in the nucleus dependently on nuclear ACSS2, contributing to epigenetic regulation of lipogenesis in hepatic steatosis. Targeting ACSS2 may be a potential therapeutical strategy for acute alcoholic liver steatosis.
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Acetato CoA Ligasa , Hígado Graso Alcohólico , Hígado Graso , Hepatopatías Alcohólicas , Animales , Ratones , Acetilcoenzima A/genética , Acetilcoenzima A/metabolismo , Epigénesis Genética , Etanol , Hígado Graso/genética , Hígado Graso Alcohólico/genética , Histonas , Lipogénesis/genética , Hígado/metabolismo , Hepatopatías Alcohólicas/metabolismo , Acetato CoA Ligasa/genética , Acetato CoA Ligasa/metabolismoRESUMEN
Renal cell carcinoma is one of the most common malignancies worldwide, and kidney renal clear cell carcinoma (KIRC) is the most common histopathological type of renal cell carcinoma. However, the mechanism of KIRC progression remains poorly understood. Apolipoprotein M (ApoM) is a plasma apolipoprotein and a member of the lipid transport protein superfamily. Lipid metabolism is essential for tumor progression, and its related proteins can be used as therapeutic targets for tumors. ApoM influences the development of several cancers, but its relationship with KIRC remains unclear. In this study, we aimed to investigate the biological function of ApoM in KIRC and to reveal its potential molecular mechanisms. We found that ApoM expression was significantly reduced in KIRC and was strongly correlated with patient prognosis. ApoM overexpression significantly inhibited KIRC cell proliferation in vitro, suppressed the epithelial mesenchymal transition (EMT) of KIRC cells, and decreased their metastatic capacity. Additionally, the growth of KIRC cells was inhibited by ApoM overexpression in vivo. In addition, we found that overexpression of ApoM in KIRC attenuated Hippo-YAP protein expression and YAP stability and thus inhibited KIRC growth and progression. Therefore, ApoM may be a potential target for the treatment of KIRC.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Apolipoproteínas M/metabolismo , Carcinoma de Células Renales/metabolismo , Línea Celular Tumoral , Riñón/patología , Neoplasias Renales/metabolismo , Transducción de Señal , Proteínas Señalizadoras YAPRESUMEN
Malfunction of the sialic acid transporter caused by various genetic mutations in the SLC17A5 gene encoding Sialin leads to a spectrum of neurodegenerative conditions called free sialic acid storage disorders. Unfortunately, how Sialin transports sialic acid/proton (H+) and how pathogenic mutations impair its function are poorly defined. Here, we present the structure of human Sialin in an inward-facing partially open conformation determined by cryo-electron microscopy, representing the first high-resolution structure of any human SLC17 member. Our analysis reveals two unique features in Sialin: (i) The H+ coupling/sensing requires two highly conserved Glu residues (E171 and E175) instead of one (E175) as implied in previous studies; and (ii) the normal function of Sialin requires the stabilization of a cytosolic helix, which has not been noticed in the literature. By mapping known pathogenic mutations, we provide mechanistic explanations for corresponding functional defects. We propose a structure-based mechanism for sialic acid transport mediated by Sialin.
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Enfermedad por Almacenamiento de Ácido Siálico , Simportadores , Humanos , Ácido N-Acetilneuramínico , Microscopía por Crioelectrón , Enfermedad por Almacenamiento de Ácido Siálico/genética , Mutación , Simportadores/genética , Simportadores/metabolismo , Transporte IónicoRESUMEN
Benzotriazole ultraviolet stabilizers (BUVSs) have been reported to induce inflammatory responses which may promote cholesterol accumulation and to downregulate the expression of genes involved in cholesterol biosynthesis; hence, we speculated whether BUVSs promote foam cell formation, which plays a key role in all stages of atherosclerosis. Herein, we used high-content imaging to screen all available BUVSs; of all the 17 candidates, 6 of them could promote foam cell formation at 10 µM. Further analyses showed that one BUVS UV-234 markedly increased the foam cell staining intensity by 15.0%-55.9% in the 0.5-10 µM exposure groups in a dose-dependent manner. Cholesterol influx was markedly enhanced by 21.0%-24.5% in the 5-10 µM exposure groups and cholesterol efflux was downregulated by 21.2%-59.3% in the 0.5-10 µM exposure groups, indicating that cholesterol efflux may play a major role in foam formation considering cholesterol efflux was downregulated at a relatively low concentration. Gene expression of ABCA1 and ABCG1 which regulate the cholesterol efflux were also decreased at 0.5-10 µM. The degradation of hypoxia-inducible factor 1α (HIF1α) via the ubiquitin-proteasome system was observed at 0.5-10 µM, probably contributing to the downregulated expression of the genes encoding liver X receptors (LXR) α/ß and their targets, ABCA1 and ABCG1. Thus, our study revealed that BUVSs frequently detected in the environment can promote foam cell formation in macrophages, contributing to the risk of atherosclerosis in humans.
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Aterosclerosis , Células Espumosas , Humanos , Macrófagos/metabolismo , ColesterolRESUMEN
Based on the big data and survey data of online recruitment platform, this paper empirically tests the impact of COVID-19 on the employment status and psychological expectations of college graduates. The results show that: under the impact of COVID-19 epidemic, both supply and demand sides of college graduates' employment market are affected, such as the decline of recruitment demand, the rise of the employment supply, and the obvious decrease of employment market prosperity. The impacts of COVID-19 epidemic on college graduates' employment status and psychological expectation in different cities are heterogeneous. In the short term, the epidemic has a negative impact on the employment of graduates, but the employment situation is gradually improving with the support of national policies. Under the influence of COVID-19 epidemic, graduates will change their employment location and expected salary, and they tend to choose "temporary non-employment," and their proportions of getting offers and signing contracts are significantly reduced. This paper suggests: Firstly, we should continue to push forward the action plan of "expanding jobs in graduation season to promote employment," and strengthen the persistence and permanence of employment promotion policies for college graduates; Secondly, encourage college students to change their employment concept and rationally adjust their employment expectations; Thirdly, to promote the development of flexible employment of college graduates, it is necessary to strengthen the propaganda of flexible employment, so that students can understand relevant policies; Fourthly, strengthen employment guidance services for graduates from poor families to ensure the continuity and stability of employment assistance policies.