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1.
Ann Gen Psychiatry ; 23(1): 15, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38664741

RESUMEN

BACKGROUND: Patients with mood disorders usually require repeated and prolonged hospitalization, resulting in a heavy burden on healthcare resources. This study aims to identify variables associated with length of stay(LOS) of repeatedly hospitalized patients with mood disorders and to provide information for optimizing psychiatry management and healthcare resource allocation. METHODS: Electronic medical records (EMRs) of repeatedly hospitalized patients with mood disorders from January 2010 to December 2018 were collected and retrospectively analyzed. Chi-square and t-test were adopted to investigate the differences in characteristics between the two groups of short LOS and long LOS. Generalized estimating equation (GEE) was conducted to investigate potential factors influencing LOS. RESULTS: A total of 2,009 repeatedly hospitalized patients with mood disorders were enrolled, of which 797 (39.7%) had a long LOS and 1,212 (60.3%) had a short LOS. Adverse effects of treatment, continuous clinical manifestation, chronic onset type, suicide attempt, comorbidity and use of antidepressants were positively associated with long LOS among all repeatedly hospitalized patients with mood disorders (P < 0.050). For patients with depression, factors associated with long LOS consisted of age, monthly income, adverse effects of treatment, continuous clinical manifestation, suicide attempt and comorbidity (P < 0.050). Whereas, for patients with bipolar disorder (BD), adverse effects of treatment, four or more hospitalizations and use of antidepressants contributed to the long LOS (P < 0.050). Influencing factors of LOS also vary among patients with different effectiveness of treatment. CONCLUSION: The LOS in repeatedly hospitalized patients with mood disorders was influenced by multiple factors. There were discrepancies in the factors affecting LOS in patients with different diagnoses and effectiveness of treatment, and specific factors should be addressed when evaluating the LOS.

3.
Nucleic Acids Res ; 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38647069

RESUMEN

SifiNet is a robust and accurate computational pipeline for identifying distinct gene sets, extracting and annotating cellular subpopulations, and elucidating intrinsic relationships among these subpopulations. Uniquely, SifiNet bypasses the cell clustering stage, commonly integrated into other cellular annotation pipelines, thereby circumventing potential inaccuracies in clustering that may compromise subsequent analyses. Consequently, SifiNet has demonstrated superior performance in multiple experimental datasets compared with other state-of-the-art methods. SifiNet can analyze both single-cell RNA and ATAC sequencing data, thereby rendering comprehensive multi-omic cellular profiles. It is conveniently available as an open-source R package.

4.
Front Immunol ; 15: 1357638, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38576608

RESUMEN

Objectives: With the increasing number of people worldwide infected with SARS-CoV-2, the likelihood of co-infection and/or comorbidities is rising. The impact of these co-infections on the patient's immune system remains unclear. This study aims to investigate the immunological characteristics of secondary infections in hospitalized COVID-19 patients, and preliminarily predict potential therapeutic effects of traditional Chinese medicine and their derivatives for the treatment of co-infections. Methods: In this retrospective cohort study, we included 131 hospitalized patients with laboratory-confirmed COVID-19, of whom there were 64 mild and 67 severe cases. We analyzed clinical characteristics and immunologic data, including circulating immune cell numbers, levels of inflammatory factors and viral load, comparing COVID-19 patients with and without co-infection. Results: Among 131 hospitalized COVID-19 patients, 41 (31.3%) were co-infection positive, with 33 (80.5%) having severe disease and 14 (34.1%) of them resulting in fatalities. Co-infected patients exhibited significantly higher severity and mortality rates compared to non-co-infected counterparts. Co-infected patients had significantly lower absolute counts of lymphocytes, total T lymphocytes, CD4+ T cells, CD8+ T cells and B lymphocytes, while levels of hs-CRP, PCT and IL-6 were significantly elevated compared to non-co-infected patients. Additionally, the viral load of co-infected patients was significantly higher than non-co-infected patients. Conclusion: Co-infection emerges as a dangerous factor for COVID-19 patients, elevating the risk of severe pneumonia and mortality. Co-infection suppresses the host's immune response by reducing the number of lymphocytes and increasing inflammation, thereby diminishing the antiviral and anti-infective effects of the immune system, which promotes the severity of the disease. Therefore, it is crucial to implement infection prevention measures to minimize the spread of co-infections among COVID-19 hospitalized patients. Additionally, changes in these biomarkers provide a theoretical basis for the effective treatment of co-infections with traditional Chinese medicine.


Asunto(s)
COVID-19 , Coinfección , Humanos , Coinfección/epidemiología , SARS-CoV-2 , Linfocitos T CD8-positivos , Estudios Retrospectivos , Medicina Tradicional China
5.
BMC Public Health ; 24(1): 1035, 2024 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-38614987

RESUMEN

INTRODUCTION: Widespread concern exists in today's world regarding self-harm and interpersonal violence. This study to analyze the changes in temporal trends and spatial patterns of risk factors and burdens of self-harm and interpersonal violence using the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. METHODS: Temporal trends in self-harm and interpersonal violence were initially summarized using the estimated annual percentage change (EAPC). Data were compiled and visualized to delineate changes in disease burden and factors influencing self-harm and interpersonal violence from 1990 to 2019, stratified by gender, age and GBD region. RESULTS: In 2019, the DALY rates of self-harm were 424.7(95% UI 383.25, 466.93). Over the period from 1999 to 2019, self-harm exhibited an overall decreasing trend, with the EAPC of -1.5351 (95% CI -1.6194, -1.4507), -2.0205 (95% CI -2.166, -1.8740) and -2.0605 (95% CI -2.2089, -1.9119), respectively. In contrast, the incidence rate of interpersonal violence was significantly higher than self-harm, with a rate of 413.44 (95% UI 329.88, 502.37) per 100,000 population. Mortality and DALYs of interpersonal violence were lower than those of self-harm, at 5.22 (95% UI 4.87, 5.63) and 342.43 (95% UI 316.61, 371.55). Disease burden of self-harm and interpersonal violence varied by gender, age groups and region. Specific risk factors showed that alcohol use, high temperature and drug use were the main risk factors for self-harm, while alcohol use, intimate partner violence and high temperature were associated with interpersonal violence. Low temperature was a common protective factor for both self-harm and interpersonal violence. The burden of self-harm and interpersonal violence was attributed to different factors influences in different SDI regions. CONCLUSIONS: The study explored temporal trends and spatial distribution of the global disease burden of self-harm and interpersonal violence, emphasizing the significant impact of factors such as alcohol use, temperature, and drug use on disease burden. Further research and policy actions are needed to interpret recent changes of disease burden of self-harm and interpersonal violence, and dedicated efforts should be implemented to devise evidence-based interventions and policies to curtail risk factors and protect high-risk groups.


Asunto(s)
Violencia de Pareja , Conducta Autodestructiva , Humanos , Carga Global de Enfermedades , Conducta Autodestructiva/epidemiología , Consumo de Bebidas Alcohólicas , Factores de Riesgo
6.
Anal Chem ; 96(16): 6158-6169, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38602477

RESUMEN

Raman spectroscopy has been widely used for label-free biomolecular analysis of cells and tissues for pathological diagnosis in vitro and in vivo. AI technology facilitates disease diagnosis based on Raman spectroscopy, including machine learning (PCA and SVM), manifold learning (UMAP), and deep learning (ResNet and AlexNet). However, it is not clear how to optimize the appropriate AI classification model for different types of Raman spectral data. Here, we selected five representative Raman spectral data sets, including endometrial carcinoma, hepatoma extracellular vesicles, bacteria, melanoma cell, diabetic skin, with different characteristics regarding sample size, spectral data size, Raman shift range, tissue sites, Kullback-Leibler (KL) divergence, and significant Raman shifts (i.e., wavenumbers with significant differences between groups), to explore the performance of different AI models (e.g., PCA-SVM, SVM, UMAP-SVM, ResNet or AlexNet). For data set of large spectral data size, Resnet performed better than PCA-SVM and UMAP. By building data characteristic-assisted AI classification model, we optimized the network parameters (e.g., principal components, activation function, and loss function) of AI model based on data size and KL divergence etc. The accuracy improved from 85.1 to 94.6% for endometrial carcinoma grading, from 77.1 to 90.7% for hepatoma extracellular vesicles detection, from 89.3 to 99.7% for melanoma cell detection, from 88.1 to 97.9% for bacterial identification, from 53.7 to 85.5% for diabetic skin screening, and mean time expense of 5 s.


Asunto(s)
Espectrometría Raman , Espectrometría Raman/métodos , Humanos , Femenino , Neoplasias Endometriales/patología , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/química , Aprendizaje Automático , Melanoma/patología , Melanoma/diagnóstico , Melanoma/clasificación , Vesículas Extracelulares/química , Máquina de Vectores de Soporte , Bacterias/clasificación , Bacterias/aislamiento & purificación , Inteligencia Artificial
7.
Cell Signal ; 119: 111180, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38642782

RESUMEN

CXXC5, a zinc-finger protein, is known for its role in epigenetic regulation via binding to unmethylated CpG islands in gene promoters. As a transcription factor and epigenetic regulator, CXXC5 modulates various signaling processes and acts as a key coordinator. Altered expression or activity of CXXC5 has been linked to various pathological conditions, including tumorigenesis. Despite its known role in cancer, CXXC5's function and mechanism in ovarian cancer are unclear. We analyzed multiple public databases and found that CXXC5 is highly expressed in ovarian cancer, with high expression correlating with poor patient prognosis. We show that CXXC5 expression is regulated by oxygen concentration and is a direct target of HIF1A. CXXC5 is critical for maintaining the proliferative potential of ovarian cancer cells, with knockdown decreasing and overexpression increasing cell proliferation. Loss of CXXC5 led to inactivation of multiple inflammatory signaling pathways, while overexpression activated these pathways. Through in vitro and in vivo experiments, we confirmed ZNF143 and EGR1 as downstream transcription factors of CXXC5, mediating its proliferative potential in ovarian cancer. Our findings suggest that the CXXC5-ZNF143/EGR1 axis forms a network driving ovarian cell proliferation and tumorigenesis, and highlight CXXC5 as a potential therapeutic target for ovarian cancer treatment.

8.
J Exp Clin Cancer Res ; 43(1): 123, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38654325

RESUMEN

BACKGROUND: Aberrant fucosylation observed in cancer cells contributes to an augmented release of fucosylated exosomes into the bloodstream, where miRNAs including miR-4732-3p hold promise as potential tumor biomarkers in our pilot study. However, the mechanisms underlying the sorting of miR-4732-3p into fucosylated exosomes during lung cancer progression remain poorly understood. METHODS: A fucose-captured strategy based on lentil lectin-magnetic beads was utilized to isolate fucosylated exosomes and evaluate the efficiency for capturing tumor-derived exosomes using nanoparticle tracking analysis (NTA). Fluorescence in situ hybridization (FISH) and qRT-PCR were performed to determine the levels of miR-4732-3p in non-small cell lung cancer (NSCLC) tissue samples. A co-culture system was established to assess the release of miRNA via exosomes from NSCLC cells. RNA immunoprecipitation (RIP) and miRNA pull-down were applied to validate the interaction between miR-4732-3p and heterogeneous nuclear ribonucleoprotein K (hnRNPK) protein. Cell functional assays, cell derived xenograft, dual-luciferase reporter experiments, and western blot were applied to examine the effects of miR-4732-3p on MFSD12 and its downstream signaling pathways, and the impact of hnRNPK in NSCLC. RESULTS: We enriched exosomes derived from NSCLC cells using the fucose-captured strategy and detected a significant upregulation of miR-4732-3p in fucosylated exosomes present in the serum, while its expression declined in NSCLC tissues. miR-4732-3p functioned as a tumor suppressor in NSCLC by targeting 3'UTR of MFSD12, thereby inhibiting AKT/p21 signaling pathway to induce cell cycle arrest in G2/M phase. NSCLC cells preferentially released miR-4732-3p via exosomes instead of retaining them intracellularly, which was facilitated by the interaction of miR-4732-3p with hnRNPK protein for selective sorting into fucosylated exosomes. Moreover, knockdown of hnRNPK suppressed NSCLC cell proliferation, with the elevated levels of miR-4732-3p in NSCLC tissues but the decreased expression in serum fucosylated exosomes. CONCLUSIONS: NSCLC cells escape suppressive effects of miR-4732-3p through hnRNPK-mediated sorting of them into fucosylated exosomes, thus supporting cell malignant properties and promoting NSCLC progression. Our study provides a promising biomarker for NSCLC and opens a novel avenue for NSCLC therapy by targeting hnRNPK to prevent the "exosome escape" of tumor-suppressive miR-4732-3p from NSCLC cells.


Asunto(s)
Progresión de la Enfermedad , Exosomas , Ribonucleoproteína Heterogénea-Nuclear Grupo K , Neoplasias Pulmonares , MicroARNs , Humanos , Exosomas/metabolismo , Exosomas/genética , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Ratones , Animales , Ribonucleoproteína Heterogénea-Nuclear Grupo K/metabolismo , Ribonucleoproteína Heterogénea-Nuclear Grupo K/genética , Línea Celular Tumoral , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Fucosa/metabolismo , Femenino , Proliferación Celular , Masculino , Ratones Desnudos , Regulación Neoplásica de la Expresión Génica
9.
ACS Appl Bio Mater ; 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38598772

RESUMEN

Peptides are a promising skincare ingredient, but due to their inherent instability and the barrier function of the skin's surface, they often have limited skin absorption and penetration, which can significantly hinder their skincare benefits. To address this, a novel technique called NanoGlow has been introduced for encapsulating peptide-based cosmetic raw materials into engineered nanosized plant-derived exosomes (pExo) to achieve the goal of a healthier and more radiant skin state. In this approach, pExo served as carriers for cosmetic peptides across the intact skin barrier, enhancing their biological effectiveness in skin beauty. The NanoGlow strategy combines chemical activation and physical proencapsulation, boasting a high success rate and straightforward and stable operation, making it suitable for large-scale production. Comprehensive analysis using in vitro cellular absorption and skin penetration models has demonstrated that the nanosized pExo carriers significantly improve peptide penetration into the skin compared to free peptides. Furthermore, in vivo tissue slice studies have shown that pExo carriers efficiently deliver acetyl hexapeptide-8 to the skin's dermis, surpassing the performance of free peptides. Cosmetic skincare effect analysis has also indicated that pExo-loaded cosmetic peptides deliver superior results. Therefore, the NanoGlow technique harnesses the natural size and properties of pExo to maximize the bioavailability of cosmetic peptides, holding great promise for developing advanced peptide delivery systems in both the cosmetic and medical drug industries.

10.
EMBO J ; 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38600243

RESUMEN

The γ-tubulin ring complex (γ-TuRC) is a structural template for de novo microtubule assembly from α/ß-tubulin units. The isolated vertebrate γ-TuRC assumes an asymmetric, open structure deviating from microtubule geometry, suggesting that γ-TuRC closure may underlie regulation of microtubule nucleation. Here, we isolate native γ-TuRC-capped microtubules from Xenopus laevis egg extract nucleated through the RanGTP-induced pathway for spindle assembly and determine their cryo-EM structure. Intriguingly, the microtubule minus end-bound γ-TuRC is only partially closed and consequently, the emanating microtubule is locally misaligned with the γ-TuRC and asymmetric. In the partially closed conformation of the γ-TuRC, the actin-containing lumenal bridge is locally destabilised, suggesting lumenal bridge modulation in microtubule nucleation. The microtubule-binding protein CAMSAP2 specifically binds the minus end of γ-TuRC-capped microtubules, indicating that the asymmetric minus end structure may underlie recruitment of microtubule-modulating factors for γ-TuRC release. Collectively, we reveal a surprisingly asymmetric microtubule minus end protofilament organisation diverging from the regular microtubule structure, with direct implications for the kinetics and regulation of nucleation and subsequent modulation of microtubules during spindle assembly.

11.
Artículo en Inglés | MEDLINE | ID: mdl-38600737

RESUMEN

It is of great significance to establish a low-cost, high-efficiency, self-powered micrometeorological monitoring system for agriculture, animal husbandry, and transportation. However, each additional detection element in the meteorological monitoring system increases the power consumption of the whole system by about 0.7 W. As a renewable energy technology, a triboelectric nanogenerator has the advantages of low price and self-powered sensing. To reduce the power consumption of the micrometeorological monitoring system, this work introduces an innovative solution: the wind-gathering enhanced triboelectric-electromagnetic hybrid generator (WGE-TEHG). Coupling the thin-film vibrating triboelectric nanogenerator (TENG) and electromagnetic generator (EMG), the TENG is used to monitor wind direction and the EMG is used to monitor wind speed and provide energy needed by the system. In particular, the TENG can be used as a self-powered sensor to reduce the power consumption of the sensing system. Besides, the TENG is used to produce slit effect to enhance the output performance of EMG. The experimental results show that the WGE-TEHG can build a self-powered natural environment micrometeorological sensing system. It can monitor the wind direction, wind speed, temperature, and relative humidity. This research has great application value for the self-powered sensing implementation of a hybrid TENG and EMG.

12.
Artículo en Inglés | MEDLINE | ID: mdl-38595101

RESUMEN

INTRODUCTION: Patients with myelopathy or radiculopathy commonly undergo anterior cervical fusion surgery (ACFS), which has a notable failure rate on occasion. The goal of this study was to compare revision and nonrevision surgery patients in cervical sagittal alignment (CSA) subsequent to ACFS; additionally, to identify the best CSA parameters for predicting clinical outcome after ACFS; and furthermore, to create an equation model to assist surgeons in making decisions on patients undergoing ACFS. METHODS: The data of 99 patients with symptomatic cervical myelopathy/radiculopathy who underwent ACFS were analyzed. Patients were divided into group A (underwent revision surgery after the first surgery failed) and group B (underwent only the first surgery). We measured and analyzed both preoperative and postoperative CSA parameters, including C2 slope, T1 slope, cervical lordosis C2-C7 (CL), C2-C7 sagittal vertical axis (C2C7 SVA), occiput-C2 lordosis angle (C0-C2), and chin brow vertical angle, and we further computed the correlation between the CSA parameters and created a prediction model. RESULTS: The (T1S-CL)-C2S mismatch differed significantly between groups A and B ([9.95 ± 9.95]0, [3.79 ± 6.58]0, P < 0.05, respectively). A significant correlation was observed between C2 slope and T1CL in group B relative to group A postoperatively (R2 = 0.42 versus R2 = 0.09, respectively). Compared with group B, patients in group A had significantly higher C2C7SVA values, more levels of fusion, and more smokers. The sensitivity, specificity, accuracy, and discrimination of the model were, respectively, 73.5%, 84%, 78.8%, and 85.65%. CONCLUSION: The causes of revision surgery in cervical myelopathic patients after anterior cervical corpectomy and fusion/anterior cervical diskectomy and fusion are multifactorial. (T1S-CL)-C2S mismatch and high C2C7SVA are the best cervical sagittal parameters that increase the odds of revision surgery, and the effect is more enhanced when comorbidities such as smoking, low bone-mineral density, and increased levels of fusion are taken into account.

13.
Integr Zool ; 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38597117

RESUMEN

Golden snub-nosed monkeys show inconsistent frequency of placentophagy between wild and captive populations, with almost all births in the wild but around half of the births in captivity accompanied by the female's consumption of placenta. This aligns with nutritional demands-driven placentophagy, as captive populations are generally under less nutritional constraints for breeding females than the wild population. Placentophagy is probably adaptive in the wild and under positive selection due to nutritional benefits to both mothers and infants.

14.
J Environ Manage ; 357: 120776, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38579468

RESUMEN

Hydro-Fluctuation Belt (HFB), a periodically exposed bank area formed by changes in water level fluctuations, is critical for damaging the reservoir wetland landscape and ecological balance. Thus, it is important to explore the mechanism of hydrological conditions on the plant-soil system of the HFB for protection of the reservoir wetland and landscape restoration. Here, we investigated the response of plant community characteristics and soil environment of the HFB of Tonghui River National Wetland Park (China), is a typical reservoir wetland, to the duration of inundation, as well as the correlation between the distribution of dominant plants and soil pH, nutrient contents, and enzyme activity by linear regression and canonical correlation analyses. The results show that as the duration of inundation decreases, the vegetation within the HFB is successional from annual or biennial herbs to perennial herbs and shrubs, with dominant plant species prominent and uneven distribution of species. Soil nutrient contents and enzyme activities of HFB decreased with increasing inundation duration. Dominant species of HFB plant community are related to soil environment, with water content, pH, urease, and available potassium being principle soil environmental factors affecting their distribution. When HFB was inundated for 0-30 days, soil pH was strongly acidic, with available potassium content above 150 mg kg-1 and higher urease activity, distributed with Arundo donax L., Polygonum perfoliatum L., Alternanthera philoxeroides (Mart.) Griseb., and Daucus carota L. communities. When inundated for 30-80 days, soil pH was acidic, with lower available potassium content (50-150 mg kg-1) and urease activity, distributed with Beckmannia syzigachne (Steud.) Fern.+ Polygonum lapathifolium L., Polygonum lapathifolium L., Medicago lupulina L. + Dysphania ambrosioides L. and Leptochloa panicea (Retz.) Ohwi communities. Using the constructed HFB plant-soil correlation model, changes in the wetland soil environment can be quickly judged by the succession of plant dominant species, which provides a simpler method for the monitoring of the soil environment in the reservoir wetland, and is of great significance for the scientific management and reasonable protection of the reservoir-type wetland ecosystem.


Asunto(s)
Ecosistema , Humedales , Suelo/química , Ureasa , Plantas , Agua , Poaceae , China , Potasio
15.
Opt Express ; 32(4): 5737-5747, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38439292

RESUMEN

Dual-wavelength fiber lasers operating with a wide spectral separation are of considerable importance for many applications. In this study, we propose and experimentally explore an all-fiberized dual-wavelength random fiber laser with bi-directional laser output operating at 1064 and 1550 nm, respectively. A specially designed Er/Yb co-doped fiber, by optimizing the concentrations of the co-doped Er, Yb, Al and P, was developed for simultaneously providing Er ions gain and Yb ions gain for RFL. Two spans of single mode passive fibers are employed to providing random feedback for 1064 and 1550 nm random lasing, respectively. The RFL generates 5.35 W at 1064 nm and 6.61 W at 1550 nm random lasers. Two power amplifiers (PA) enhance the seed laser to 50 W at 1064 nm with a 3 dB bandwidth of 0.31 nm and 20 W at 1550 nm with a 3 dB bandwidth of 1.18 nm. Both the short- and long-term time domain stabilities are crucial for practical applications. The output lasers of 1064 and 1550 nm PAs are in the single transverse mode operating with a nearly Gaussian profile. To the best of our knowledge, this is the first demonstration of a dual-wavelength RFL, with a spectral separation as far as about 500 nm in an all-fiber configuration.

16.
Nat Commun ; 15(1): 1908, 2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38459023

RESUMEN

Liver injury is a core pathological process in the majority of liver diseases, yet the genetic factors predisposing individuals to its initiation and progression remain poorly understood. Here we show that asialoglycoprotein receptor 1 (ASGR1), a lectin specifically expressed in the liver, is downregulated in patients with liver fibrosis or cirrhosis and male mice with liver injury. ASGR1 deficiency exacerbates while its overexpression mitigates acetaminophen-induced acute and CCl4-induced chronic liver injuries in male mice. Mechanistically, ASGR1 binds to an endoplasmic reticulum stress mediator GP73 and facilitates its lysosomal degradation. ASGR1 depletion increases circulating GP73 levels and promotes the interaction between GP73 and BIP to activate endoplasmic reticulum stress, leading to liver injury. Neutralization of GP73 not only attenuates ASGR1 deficiency-induced liver injuries but also improves survival in mice received a lethal dose of acetaminophen. Collectively, these findings identify ASGR1 as a potential genetic determinant of susceptibility to liver injury and propose it as a therapeutic target for the treatment of liver injury.


Asunto(s)
Acetaminofén , Hígado , Animales , Humanos , Masculino , Ratones , Acetaminofén/toxicidad , Receptor de Asialoglicoproteína/genética , Receptor de Asialoglicoproteína/metabolismo , Estrés del Retículo Endoplásmico , Fibrosis , Hígado/metabolismo , Cirrosis Hepática/patología
17.
Chem Biol Interact ; 394: 110979, 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38555046

RESUMEN

TGF-ß/Smad signaling pathway plays an important role in the pathogenesis and progression of liver fibrosis. Silent information regulator 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+) dependent enzyme and responsible for deacetylating the proteins. Increasing numbers of reports have shown that the molecular mechanism of SIRT1 as an effective therapeutic target for liver fibrosis but the transformation is not very clear. In the present study, liver fibrotic tissues were screened by staining with Masson, hematoxylin-eosin staining (H&E) and Immunohistochemistry (IHC) for histopathological observation from the liver biopsy of seventy-seven rhesus monkey, which fixed with 4% paraformaldehyde (PFA) after treatment with high-fat diet (HFD) for two years. And the liver function was further determined by serum biochemical tests. The mRNA levels and protein expression of rat hepatic stellate (HSC-T6) cells were determined after treatment with Resveratrol (RSV) and Nicotinamide (NAM), respectively. The results showed that with the increasing of hepatic fibrosis in rhesus monkeys, the liver function impaired, and the transforming growth factor-ß1 (TGF-ß1), p-Smad3 (p-Smad3) and alpha-smooth muscle actin (α-SMA) was up-regulated, while SIRT1 and Smad7 were down-regulated. Moreover, when stimulated the HSC-T6 with RSV to activate SIRT1 for 6, 12, and 24 h, the results showed that RSV promoted the expression of smad7, while the expression of TGF-ß1, p-Smad3 and α-SMA were inhibited. In contrast, when the cells stimulated with NAM to inhibit SIRT1 for 6, 12, and 24 h, the Smad7 expression was decreased, while TGF-ß1, p-Smad3, and α-SMA expressions were increased. These results indicate that SIRT1 acts as an important protective factor for liver fibrosis, which may be attributed to inhibiting the signaling pathway of TGF-ß/Smad in hepatic fibrosis of the rhesus monkey.

18.
PLoS Pathog ; 20(3): e1012103, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38489378

RESUMEN

Alphacoronaviruses are the primary coronaviruses responsible for causing severe economic losses in the pig industry with the potential to cause human outbreaks. Currently, extensive studies have reported the essential role of endosomal sorting and transport complexes (ESCRT) in the life cycle of enveloped viruses. However, very little information is available about which ESCRT components are crucial for alphacoronaviruses infection. By using RNA interference in combination with Co-immunoprecipitation, as well as fluorescence and electron microscopy approaches, we have dissected the role of ALIX and TSG101 for two porcine alphacoronavirus cellular entry and replication. Results show that infection by two porcine alphacoronaviruses, including porcine epidemic diarrhea virus (PEDV) and porcine enteric alphacoronavirus (PEAV), is dramatically decreased in ALIX- or TSG101-depleted cells. Furthermore, PEDV entry significantly increases the interaction of ALIX with caveolin-1 (CAV1) and RAB7, which are crucial for viral endocytosis and lysosomal transport, however, does not require TSG101. Interestingly, PEAV not only relies on ALIX to regulate viral endocytosis and lysosomal transport, but also requires TSG101 to regulate macropinocytosis. Besides, ALIX and TSG101 are recruited to the replication sites of PEDV and PEAV where they become localized within the endoplasmic reticulum and virus-induced double-membrane vesicles. PEDV and PEAV replication were significantly inhibited by depletion of ALIX and TSG101 in Vero cells or primary jejunal epithelial cells, indicating that ALIX and TSG101 are crucial for PEDV and PEAV replication. Collectively, these data highlight the dual role of ALIX and TSG101 in the entry and replication of two porcine alphacoronaviruses. Thus, ESCRT proteins could serve as therapeutic targets against two porcine alphacoronaviruses infection.


Asunto(s)
Alphacoronavirus , Proteínas de Unión al Calcio , Virus de la Diarrea Epidémica Porcina , Animales , Alphacoronavirus/metabolismo , Línea Celular , Chlorocebus aethiops , Complejos de Clasificación Endosomal Requeridos para el Transporte/metabolismo , Células Epiteliales/metabolismo , Virus de la Diarrea Epidémica Porcina/metabolismo , Porcinos , Células Vero , Replicación Viral , Proteínas de Unión al Calcio/metabolismo
19.
Environ Sci Pollut Res Int ; 31(16): 24599-24618, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38446301

RESUMEN

The balance between human growth, economic prosperity, and the consumption of hydrocarbon energy factors has become a prerequisite for environmental sustainability. However, the complexities of these factors force researchers to work for more viable combinations of such a balance. Therefore, this study attempted to determine the factors driving environmental sustainability in leading populated economies. For this purpose, the Logarithmic Mean Division Index (LMDI) utilized to decompose critical factors such as activity, economy, real density, energy intensity, and suburban effects for the period 1999-2022. Both population and its consequences (economic activity) have been found to be the leading factors behind environmental fluctuations, and energy has a negative impact on hydrocarbon forms, while contributing positively to environmental sustainability with high efficiency and low intensity. Therefore, sustainable demographic and energy transitions can be leading pathways for environmental sustainability in developing economies.


Asunto(s)
Factores Sociales , Desarrollo Sostenible , Humanos , Dióxido de Carbono , Desarrollo Económico , Hidrocarburos , Energía Renovable
20.
Molecules ; 29(6)2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38543035

RESUMEN

To investigate the influence of deashing on fusion characteristics, a combined method of water and acid washing with different sequences (water washing followed by acid washing, and acid washing followed by water washing) was used to treat the biochar of bamboo shoot shells (BBSSs). The results show that deashing decreased the K content of the biochar from 50.3% to 1.08% but increased the Si content from 33.48% to 89.15%. The formation of silicates and aluminosilicates from alkali metal oxides with silicon was an inevitable result of ash phase transformation at the high temperatures used to improve the fusion temperature (>1450 °C). The thermochemical behavior of ash mainly occurs at 1000 °C. The deashing treatment significantly reduced the reaction intensity during the high-temperature process. This significantly increased the thermal stability of the ash. The adjustment of the washing sequence had a slight impact on the chemical compositions, but the differences in ash micromorphology were obvious. Deashing treatments with different washing sequences can significantly improve ash fusion properties effectively and reduce the risk of scaling, slagging, and corrosion. This study provides a new and reasonable strategy for the deashing of biochar to commercially utilize bamboo shoot shell resources.


Asunto(s)
Álcalis , Carbón Orgánico , Carbón Orgánico/química , Temperatura , Agua , Ceniza del Carbón
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