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1.
BMJ Open Respir Res ; 11(1)2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38599779

RESUMO

BACKGROUND: In China, both nirmatrelvir-ritonavir (Paxlovid) and azvudine have been granted approval to treat adult SARS-CoV-2-infected patients with moderate symptoms. Information about the clinical effect of the two available agents among inpatients with severe or critical COVID-19 is scarce. PURPOSE: To compare the clinical outcomes of Paxlovid and azvudine among adult inpatients with severe or critical COVID-19. METHOD: We conducted a retrospective cohort study in two large medical centres after the epidemic control measures were lifted in China. A new propensity score matched-inverse probability of treatment weighting cohort was constructed to evaluate the in-hospital all-cause mortality, hospital length of stay, Sequential Organ Failure Assessment (SOFA) score and safety. RESULTS: A total of 955 individuals were in the cohort. The antiviral therapy strategies were decided by the senior physician and the supplies of the pharmacy. A total of 451 patients were in the Paxlovid group, and 504 patients were in the azvudine group. Compared with Paxlovid, the effects of azvudine on in-hospital all-cause mortality were not significantly different, and the OR (95% CI) was 1.084 (0.822 to 1.430), and the average hospital length of stay of patients discharged alive was also similar in the azvudine group, and the difference (day) and (95% CI) was 0.530 (-0.334 to 1.393). After 7 days of therapy, the degree of decline in the SOFA score was greater in the Paxlovid group than in the azvudine group (p<0.001). The change in glomerular filtration rate was not significantly different (p=0.824). CONCLUSION: Paxlovid and azvudine had similar effectiveness on in-hospital all-cause mortality and hospital length of stay. Compared with the azvudine group, after 7 days of therapy, the degree of decline in SOFA score was significantly higher in the Paxlovid group. These findings need to be verified in larger prospective studies or randomised controlled trials.


Assuntos
Azidas , COVID-19 , Desoxicitidina/análogos & derivados , Pacientes Internados , Lactamas , Leucina , Nitrilas , Prolina , Adulto , Humanos , Ritonavir/uso terapêutico , Estudos Prospectivos , Estudos Retrospectivos , SARS-CoV-2 , Tratamento Farmacológico da COVID-19 , Combinação de Medicamentos
2.
J Exp Clin Cancer Res ; 43(1): 108, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600610

RESUMO

Ferroptosis is a newly identified iron-dependent form of death that is becoming increasingly recognized as a promising avenue for cancer therapy. N6-methyladenosine (m6A) is the most abundant reversible methylation modification in mRNA contributing to tumorigenesis. However, the crucial role of m6A modification in regulating ferroptosis during colorectal cancer (CRC) tumorigenesis remains elusive. Herein, we find that m6A modification is increased during ferroptotic cell death and correlates with the decreased m6A demethylase fat mass and obesity-associated protein (FTO) expression. Functionally, we demonstrate that suppressing FTO significantly induces CRC ferroptotic cell death, as well as enhancing CRC cell sensitivity to ferroptosis inducer (Erastin and RSL3) treatment. Mechanistically, high FTO expression increased solute carrier family 7 member 11 (SLC7A11) or glutathione peroxidase 4 (GPX4) expressions in an m6A-YTHDF2 dependent manner, thereby counteracting ferroptotic cell death stress. In addition, we identify Mupirocin as a novel inhibitor of FTO, and Mupirocin induces CRC ferroptosis and inhibits tumor growth. Clinically, the levels of FTO, SLC7A11, and GPX4, are highly correlated expression in CRC tissues. Our findings reveal that FTO protects CRC from ferroptotic cell death in promoting CRC tumorigenesis through triggering SLC7A11/GPX4 expression.


Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato , Neoplasias Colorretais , Mupirocina , Humanos , Dioxigenase FTO Dependente de alfa-Cetoglutarato/antagonistas & inibidores , Sistema y+ de Transporte de Aminoácidos , Carcinogênese , Morte Celular , Transformação Celular Neoplásica , Neoplasias Colorretais/tratamento farmacológico
3.
Int J Ophthalmol ; 17(4): 761-766, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38638243

RESUMO

AIM: To evaluate scleral buckling (SB) surgery using a non-contact wide-field viewing system and 23-gauge intraocular illumination for the treatment of rhegmatogenous retinal detachment in silicone oil (SO)-filled eyes. METHODS: Totally 9 patients (9 eyes) with retinal detachment in SO-filled eyes were retrospectively analyzed. All patients underwent non-contact wide-field viewing system-assisted buckling surgery with 23-gauge intraocular illumination. SO was removed at an appropriate time based on recovery. The patients were followed up for at least 3mo after SO removal. Retinal reattachment, complications, visual acuity and intraocular pressure (IOP) before and after surgery were observed. RESULTS: Patients were followed up for a mean of 8.22mo (3-22mo) after SO removal. All patients had retinal reattachment. At the final follow-up, visual acuity showed improvement for 8 patients, and no change for 1 patient. The IOP was high in 3 patients before surgery, but it stabilized after treatment; it was not affected in the other patients. None of the patients had infections, hemorrhage, anterior ischemia, or any other complication. CONCLUSION: This new non-contact wide-field viewing system-assisted SB surgery with 23-gauge intraocular illumination is effective and safe for retinal detachment in SO-filled eyes.

4.
Neuroimage ; : 120624, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38657745

RESUMO

Pain empathy, defined as the ability of one person to understand another person's pain, shows large individual variations. The anterior insula is the core region of the pain empathy network. However, the relationship between white matter (WM) properties of the fiber tracts connecting the anterior insula with other cortical regions and an individual's ability to modulate pain empathy remains largely unclear. In this study, we outline an automatic seed-based fiber streamline (sFS) analysis method and multivariate pattern analysis (MVPA) to predict the levels of pain empathy in healthy women and women with primary dysmenorrhoea (PDM). Using the sFS method, the anterior insula-based fiber tract network was divided into five fiber cluster groups. In healthy women, interindividual differences in pain empathy were predicted only by the WM properties of the five fiber cluster groups, suggesting that interindividual differences in pain empathy may rely on the connectivity of the anterior insula-based fiber tract network. In women with PDM, pain empathy could be predicted by a single cluster group. The mean WM properties along the anterior insular-rostroventral area of the inferior parietal lobule further mediated the effect of pain on empathy in patients with PDM. Our results suggest that chronic periodic pain may lead to maladaptive plastic changes, which could further impair empathy by making women with PDM feel more pain when they see other people experiencing pain. Our study also addresses an important gap in the analysis of the microstructural characteristics of seed-based fiber tract network.

5.
Front Microbiol ; 15: 1375384, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38659979

RESUMO

Introduction: As prebiotics, oligosaccharides are frequently combined with Bifidobacterium to develop synbiotic products. However, a highly diverse gene repertoire of Bifidobacterium is involved in sugar catabolism, and even phylogenetically close species may differ in their sugar utilization capabilities. To further explore the mechanism underlying the differences in Bifidobacterium animalis subsp. lactis oligosaccharide metabolism. Methods: This study screened strains with differential oligosaccharide metabolism. Subsequently, these strains were subjected to genome-wide resequencing and RT-qPCR. Results: The resequencing results indicated that the subspecies of B. animalis subsp. lactis had a high genome similarity. The RT-qPCR results revealed that glycosidase genes exhibited consistency in the phenotype of metabolism at the transcriptional level; the better the growth of the strains on the oligosaccharides, the higher was the expression of glycosidase genes related to the oligosaccharides. Our results suggested that the differences in the gene transcription levels led to intraspecies differences in the ability of the strains to metabolize oligosaccharides even when they belonged to the same subspecies. Discussion: Future studies with more sample size could generalizable the conclusion to all B. animalis subsp. lactis strains, thus would lay the theoretical foundation for the utilization of the B. animalis subsp. lactis strain as probiotics and the development of synbiotic products.

7.
Foods ; 13(6)2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38540916

RESUMO

Elaeagnus moorcroftii Wall.ex Schlecht. (EWS) has extensive nutrients and functional active ingredients, which makes it an excellent potential substrate for fermentation. The improvement in the antioxidant activity of Elaeagnus moorcroftii Wall.ex Schlecht. juice (EWSJ) fermented by Bifidobacterium animalis subsp. lactis HN-3 (B.an3) could be attributed to the metabolism and biotransformation of plant-based products by the bacterial strain. To reveal the underlying mechanism, non-targeted metabolomics was applied in this study. After fermentation, the structure of downregulated carbohydrates, amino acids, fatty acids, and flavonoids was changed by Bifidobacterium biotransformation (included four reductions, three hydrolyses, four isomerizations, three deglycosidations, and five other reactions). The structure of these converted upregulated products has a higher antioxidant ability to reduce free radicals than their precursors, such as the flavonoids in the form of hydrolyzed conjugates, amino acids with multiple sulfhydryls or hydroxys, carbohydrates with reactive oxygen on benzene rings and fatty acids with unsaturated bonds, short chains, and glycosides. These findings shed light on the mechanism of the metabolism and biotransformation of EWSJ by B.an3, facilitate the study of the interaction between probiotics and fermented plant-based products, and provide a theoretical basis for the development of Bifidobacterium-fermented plant products with stronger functional activities.

9.
J Inorg Biochem ; 254: 112518, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38460483

RESUMO

Cisplatin is widely used as anticancer drugs, and DNA is considered as the main target. Considering its high affinity towards cysteines and the important role of cystine containing proteins, we applied a competitive activity-based protein profiling strategy to identify protein cysteines that bind with cisplatin in HeLa cells. Living cells were treated with cisplatin at cytotoxic concentrations, then the protein was extracted. After labeling with desthiobiotin iodoacetamide (DBIA) probe, protein was precipitated, digested and isotopically labeled, subsequently the peptides were combined, and the biotinylated cysteine-containing peptides were enriched and quantified by LC-MS/MS. A total of 3571 peptides which originated from 1871 proteins were identified using the DBIA probe. Among them, 46 proteins were screened as targets, including proteins that have been identified as binding proteins by previous study. A novel cisplatin target, calpain-1 (CAPN1), was identified and validated as binding with cisplatin in vitro.


Assuntos
Antineoplásicos , Cisplatino , Humanos , Cisplatino/farmacologia , Cisplatino/química , Cromatografia Líquida , Células HeLa , Espectrometria de Massas em Tandem , Antineoplásicos/farmacologia , Antineoplásicos/química , Proteínas , Cisteína/química , Peptídeos
10.
NPJ Precis Oncol ; 8(1): 73, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38519580

RESUMO

Tertiary lymphoid structures (TLSs) have been associated with favorable immunotherapy responses and prognosis in various cancers. Despite their significance, their quantification using multiplex immunohistochemistry (mIHC) staining of T and B lymphocytes remains labor-intensive, limiting its clinical utility. To address this challenge, we curated a dataset from matched mIHC and H&E whole-slide images (WSIs) and developed a deep learning model for automated segmentation of TLSs. The model achieved Dice coefficients of 0.91 on the internal test set and 0.866 on the external validation set, along with intersection over union (IoU) scores of 0.819 and 0.787, respectively. The TLS ratio, defined as the segmented TLS area over the total tissue area, correlated with B lymphocyte levels and the expression of CXCL13, a chemokine associated with TLS formation, in 6140 patients spanning 16 tumor types from The Cancer Genome Atlas (TCGA). The prognostic models for overall survival indicated that the inclusion of the TLS ratio with TNM staging significantly enhanced the models' discriminative ability, outperforming the traditional models that solely incorporated TNM staging, in 10 out of 15 TCGA tumor types. Furthermore, when applied to biopsied treatment-naïve tumor samples, higher TLS ratios predicted a positive immunotherapy response across multiple cohorts, including specific therapies for esophageal squamous cell carcinoma, non-small cell lung cancer, and stomach adenocarcinoma. In conclusion, our deep learning-based approach offers an automated and reproducible method for TLS segmentation and quantification, highlighting its potential in predicting immunotherapy response and informing cancer prognosis.

11.
Front Cell Dev Biol ; 12: 1313610, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38481526

RESUMO

Background: Patients with Triple-negative breast cancer (TNBC) face a poor prognosis and limited therapeutic options. Current data on eribulin usage to treat TNBC is scarce. Therefore, we sought to compare the feasibility and tolerability of eribulin-based regimens with other chemotherapy regimens in patients with TNBC. Method: This retrospective study was conducted at Fujian Medical University Cancer Hospital and included 159 patients with TNBC enrolled between October 2011 and January 2023. Patients underwent treatment with eribulin-based and other chemotherapy regimens. The study's primary endpoints were progression-free survival (PFS) and overall survival (OS), while its secondary endpoint was objective response rate (ORR), disease control rate (DCR), and safety. Tumour response was assessed using RECIST V.1.1 criteria. Results: Of the 159 participants in the study, 42 individuals (26.4%) received treatment with eribulin, whereas 117 participants (73.6%) were administered alternative chemotherapy regimens, which included nab-paclitaxel-based therapy (n = 45) and platinum-based therapy (n = 51). The follow-up period for all patients ended on 31 December 2022, and the median follow-up time was 18.3 months (range:0.7-27.5). Following propensity score matching (PSM), eribulin-based treatment resulted in longer median progression-free survival compared to platinum-based (hazard ratio (HR) = 0.41, p = 0.006), nab-paclitaxel-based (hazard ratio = 0.36, p = 0.001) and other chemotherapy (HR = 0.39, p < 0.001). Also, eribulin induced a remarkable prolongation of the median overall survival duration in all three comparative groups. The group receiving eribulin treatment showed significantly reduced incidences of any grade of anaemia, peripheral neuropathy, nausea and vomiting, and hair loss compared to other chemotherapy groups. Conclusion: For the salvage treatment of advanced TNBC, treatment with eribulin produced longer median PFS and OS than other chemotherapy regimens, with a well-tolerated safety profile. Therefore, further investigation of eribulin-based treatment in larger randomized trials for patients with advanced TNBC is warranted.

12.
Polymers (Basel) ; 16(4)2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38399923

RESUMO

Polyimide (PI) has been widely used in cable insulation, thermal insulation, wind power protection, and other fields due to its high chemical stability and excellent electrical insulation and mechanical properties. In this research, a modified PI composite film (MoS2@PDA/PI) was obtained by using polydopamine (PDA)-coated molybdenum disulfide (MoS2) as a filler. The low interlayer friction characteristics and high elastic modulus of MoS2 provide a theoretical basis for enhancing the flexible mechanical properties of the PI matrix. The formation of a cross-linking structure between a large number of active sites on the surface of the PDA and the PI molecular chain can effectively enhance the breakdown field strength of the film. Consequently, the tensile strength of the final sample MoS2@PDA/PI film increased by 44.7% in comparison with pure PI film, and the breakdown voltage strength reached 1.23 times that of the original film. It can be seen that the strategy of utilizing two-dimensional (2D) MoS2@PDA nanosheets filled with PI provides a new modification idea to enhance the mechanical and electrical insulation properties of PI films.

13.
Bioorg Med Chem Lett ; 102: 129670, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38387692

RESUMO

Histone deacetylase 6 (HDAC6) has drawn more and more attention for its potential application in Alzheimer's disease (AD) therapy. A series of tetrahydro-ß-carboline (THßC) hydroxamic acids with aryl linker were synthesized. In enzymatic assay, all compounds exhibited nanomolar IC50 values. The most promising compound 11d preferentially inhibited HDAC6 (IC50, 8.64 nM) with approximately 149-fold selectivity over HDAC1. Molecular simulation revealed that the hydroxamic acid of 11d could bind to the zinc ion by a bidentate chelating manner. In vitro, 11d induced neurite outgrowth of PC12 cells without producing toxic effects and showed obvious neuroprotective activity in a model of H2O2-induced oxidative stress.


Assuntos
Carbolinas , Inibidores de Histona Desacetilases , Peróxido de Hidrogênio , Ratos , Animais , Desacetilase 6 de Histona , Inibidores de Histona Desacetilases/farmacologia , Peróxido de Hidrogênio/farmacologia , Ácidos Hidroxâmicos/farmacologia , Crescimento Neuronal , Histona Desacetilase 1/metabolismo , Relação Estrutura-Atividade
14.
Food Chem X ; 21: 101171, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38370297

RESUMO

The influence on and biotransformation of volatile compounds (VOCs) during fermentation of Elaeagnus moorcroftii Wall.ex Schlecht. juice (EWSJ) through single inoculation and co-inoculation of Bifidobacterium animalis subsp. lactis HN-3 (B.an3) and Lacticaseibacillus paracasei YL-29 (L.cp29) were analyzed through headspace-solid phase microextraction-gas chromatography-mass spectrometry. Compared with the B.an3- and L.cp29-fermented EWSJ, the B.an3 + L.cp29-fermented EWSJ had more increased 9 desirable flavor compositions and less decreased in or even elimination of 12 undesirable flavor compositions, and 3 new characteristic VOCs, formed through the interaction between B.an3 and L.cp29 were detected. In addition, biotransformations that led to an increase and a decrease in VOCs mainly involved 3 oxidation, 3 reduction, 1 hydrolysis, and 1 isomerization reactions. This study offers a theoretical basis for investigating the interaction effect of Lactobacillus and Bifidobacterium species on VOCs and developing lactic acid bacteria-fermented plant-based juices with lower sugar content and better flavor.

15.
Phys Rev Lett ; 132(3): 033801, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38307075

RESUMO

We systematically investigated the intrinsic mechanical flexural modes of tapered optical fibers (TOFs) with a high aspect ratio up to 3×10^{4}. Based on the near-field scattering of the hemispherical microfiber tip to the vibrating TOF evanescent field, we detected more than 320 ordered intrinsic mechanical modes through the TOF transmission spectra which was enhanced by 72 dB compared to without near-field scattering. The trend of the vibration amplitude with the mode order was similar to pendulum waves. Our results open a pathway to study the mechanical modes of photonic microstructures-nanostructures that are expected to be used in waveguide QED, cavity optomechanical, and optical sensing.

16.
BMC Cancer ; 24(1): 39, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38182995

RESUMO

PURPOSE: This investigation sought to examine the efficacy and safety of low-dose apatinib used alongside chemotherapy in the clinical management of patients with metastatic triple-negative breast cancer (TNBC) within a real-world setting, whilst comparing the outcomes with those treated solely with chemotherapy. METHODS: This case series study analyzed clinical data and treatment outcomes of 163 patients with metastatic TNBC who underwent rescue treatment at the Medical Oncology Department of Clinical Oncology, Fujian Cancer Hospital, School of Fujian Medical University, China, between October 2011 and January 2023. All the patients underwent rescue treatment with either chemotherapy alone or apatinib (250 mg/day) combined with chemotherapy. The study's primary outcome was progression-free survival (PFS), whereas the secondary outcomes included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety profiles. RESULTS: The study was designed to compare two groups [1]. Out of the 163 TNBC patients who participated in the study, 107 individuals (65.6%) received treatment based on chemotherapy, whereas 56 patients (34.4%) were given treatment based on a combination of low-dose apatinib (250 mg/day) and other treatments, including chemotherapy. After propensity score matching (PSM), the objective response rate (ORR) and disease control rate (DCR) of patients with advanced triple-negative breast cancer (TNBC) who received apatinib-based treatment were 50.0 and 90.0%, respectively, while they were 6.7 and 20.0%, respectively, for the chemotherapy-based group (P < 0.001). The group that received apatinib-based treatment showed superior results in both PFS and OS compared to the group that received chemotherapy. The median PFS and OS for the apatinib-based group were 7.8 and 20.3 months, respectively, while they were only 2.2 months and 9.0 months, respectively, for the chemotherapy-based group (P < 0.001) [2]. Patients who were administered combo therapies, including PD-1 inhibitors, were excluded. In total, 97 patients received chemotherapy alone, while 34 patients were treated with apatinib in combination with chemotherapy. After propensity score matching (PSM), the ORR and DCR for the total group who received combo therapies were 44.4 and 81.5%, respectively, while they were 11.1 and 22.2%, respectively, for the chemotherapy alone group (P < 0.001). The group receiving both apatinib and chemotherapy displayed notable advantages over the group solely receiving chemotherapy in regards to PFS and OS for the entirety of the population. The PFS was found to be 7.8 months in comparison to 2.1 months (P < 0.001) and the OS was 21.1 months in contrast to 9.0 months (P < 0.001). Apatinib combined with chemotherapy induced grade 3/4 hematological toxicities, including neutropenia (8.8%) and thrombocytopenia (2.9%). Additionally, non-hematological toxicities were commonly observed, such as Hand-foot syndrome (35.3%), proteinuria (26.5%), hypertension (61.8%), higher alanine aminotransferase levels (26.5%), and fatigue (35.3%). The most frequent non-hematological grade 3/4 toxicities were Hand-foot syndrome (2.9%) and hypertension (5.9%). The study did not report any fatal adverse effects. CONCLUSIONS: The combination of low-dose apatinib with chemotherapy has proven to be more effective than chemotherapy alone in treating metastatic triple-negative breast cancer (TNBC). Additionally, the occurrence of grade 3/4 non-hematologic toxicities was significantly lower compared to the recommended dose of apatinib.


Assuntos
Síndrome Mão-Pé , Hipertensão , Leucopenia , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Protocolos Clínicos
17.
Signal Transduct Target Ther ; 9(1): 18, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38221551

RESUMO

Systemic lupus erythematosus (SLE), a severe autoimmune disorder, is characterized by systemic inflammatory response, autoantibody accumulation and damage to organs. The dysregulation of double-negative (DN) T cells is considered as a crucial commander during SLE. Neddylation, a significant type of protein post-translational modification (PTM), has been well-proved to regulate T cell-mediated immune response. However, the function of neddylation in SLE is still unknown. Here, we reported that neddylation inactivation with MLN4924, a specific inhibitor of NEDD8-activating enzyme E1 (NAE1), or genetic abrogation of Ube2m in T cells decreased DN T cell accumulation and attenuated murine lupus development. Further investigations revealed that inactivation of neddylation blocked Bim ubiquitination degradation and maintained Bim level in DN T cells, contributing to the apoptosis of the accumulated DN T cells in lupus mice. Then double knockout (KO) lupus-prone mice (Ube2m-/-Bim-/-lpr) were generated and results showed that loss of Bim reduced Ube2m deficiency-induced apoptosis in DN T cells and reversed the alleviated lupus progression. Our findings identified that neddylation inactivation promoted Bim-mediated DN T cell apoptosis and attenuated lupus progression. Clinically, we also found that in SLE patients, the proportion of DN T cells was raised and their apoptosis was reduced. Moreover, compared to healthy groups, SLE patients exhibited decreased Bim levels and elevated Cullin1 neddylation levels. Meantime, the inhibition of neddylation induced Bim-dependent apoptosis of DN T cells isolated from SLE patients. Altogether, our findings provide the direct evidence about the function of neddylation during lupus, suggesting a promising therapeutic approach for this disease.


Assuntos
Lúpus Eritematoso Sistêmico , Humanos , Camundongos , Animais , Ubiquitinação , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/genética , Processamento de Proteína Pós-Traducional , Linfócitos T , Homeostase
18.
Environ Int ; 183: 108354, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38043320

RESUMO

Sodium p-perfluorous nonenoxybenzenesulfonate (OBS) is a novel alternative to perfluorooctane sulfonate (PFOS), with environmental health risks largely unknown. The present study aims to unravel the adipogenesis effects and underlying molecular initiating events of OBS, which are crucial for understanding and predicting its adverse outcome. In undifferentiated human mesenchymal stem cells (hMSCs), exposure to 1-100 nM of OBS for 7 days stimulated reactive oxygen species production. In the subsequent multipotent differentiation, hMSCs favored adipogenesis and repressed osteogenesis. The point of departure (PoD) for cellular responses of OBS was 38.85 nM, higher than PFOS (0.39 nM). Notably, OBS/PFOS co-exposure inhibited osteogenesis and synergistically promoted adipogenesis. Consistently, the expression of adipogenic marker genes was up-regulated, while that of osteogenic marker genes was down-regulated. The decreased adiponectin and elevated tumor necrosis factor α (TNFα) secretion were observed in differentiated cells exposed to the mixture of OBS and PFOS. The co-treatment of a peroxisome proliferator-activated receptor γ (PPARγ) antagonist alleviated the adipogenic effects of PFOS and its combination with OBS. Moreover, OBS/PFOS co-exposure induced peroxisome PPARγ activation in reporter gene assays, and increased formation of PPARγ - retinoid X receptor α (RXRα) heterodimers measured by co-immunoprecipitation assays. Molecular docking showed interaction energy of OBS (-20.7 kcal/mol) with intact PPARγ-RXRα complex was lower than that of PFOS (-25.9 kcal/mol). Overall, single OBS exhibited lower potency in inducing adipogenesis but is comparable to PFOS in repressing osteogenesis, whereas OBS/PFOS co-exposure increases interaction with PPARγ-RXRα heterodimers, resulting in the synergistic activation of PPARγ, ultimately enhancing adipogenesis at the expense of osteogenic differentiation. The results indicate the potential health risks of increased obesity and decreased bone density caused by OBS and its co-exposure with PFOS, as well as other perfluorinated alkylated substances mixtures.


Assuntos
Adipogenia , PPAR gama , Humanos , PPAR gama/genética , Osteogênese , PPAR alfa , Simulação de Acoplamento Molecular
19.
Int J Biol Macromol ; 256(Pt 1): 128384, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38029905

RESUMO

A starch-based nanofiber mat was prepared for real-time monitoring of food freshness for the first time. UV-vis results showed that roselle anthocyanins (RS) conferred a wide pH sensing range on the nanofiber mat. The prepared nanofiber mats demonstrated good color visibility (total color difference value (ΔE) increased to 56.4 ± 0.7) and a reversible response (within 120 s). Scanning electron microscopy and Fourier transform infrared spectroscopy results suggested that the nanofibers had smooth surfaces without beaded fibers and that RS was well embedded into the nanofibers. The introduction of RS improved the thermal stability of the nanofibers. Color stability tests revealed that the nanofibers exhibited excellent color stability (maximum change ΔE = 1.57 ± 0.03) after 14 days of storage. Pork and shrimp freshness tests verified that the nanofibers could effectively reflect the dynamic freshness of pork and shrimp. Nontoxic, degradable and responsive characteristics make the pH-sensitive nanofiber mat a smart food label with great application potential.


Assuntos
Antocianinas , Nanofibras , Antocianinas/química , Nanofibras/química , Amido/química , Alimentos Marinhos , Concentração de Íons de Hidrogênio , Embalagem de Alimentos/métodos
20.
Sci Total Environ ; 913: 169625, 2024 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-38157892

RESUMO

The prevalence of shared bicycles has raised concerns over their potential to transmit pathogens and microbes harboring antibiotic resistance genes (ARGs), which pose significant human health risks. This study investigated the impact of anthropogenic activities on the composition of ARGs and microbial communities on shared bicycles during the COVID-19 pandemic and subsequent lockdown when shared bicycle usage was altered. A total of 600 swab samples from shared bicycle surfaces were collected in Shanghai before and during COVID-19 lockdown periods. Even during lockdown, 12 out of 14 initially detected ARG subtypes persisted, indicating their tenacity in the face of reduced anthropogenic activities. These ARGs displayed significantly higher absolute and relative abundance levels before the lockdown. In addition, the percentage of potential pathogens in the total microbial abundance remained at 0.029 % during the lockdown, which was lower than the pre-lockdown percentage of 0.035 % and suggested that these risks persist within shared bicycle systems. Interestingly, although microbial abundance decreased without the consecutive use of shared bicycles during lockdown, the microbial diversity increased under the impact of restricted anthropogenic activities (p < 0.001). This emphasizes the need for continuous monitoring and research to comprehend microbial community behaviors in various environments. This study uncovered the underlying impacts of the COVID-19 lockdown on the microbial and ARG communities of shared bicycles, providing comprehensive insights into the health management of shared transportation. Although lockdown can decrease the abundance of ARGs and potential pathogens, additional interventions are needed to prevent their continued spread.


Assuntos
COVID-19 , Microbiota , Humanos , Antibacterianos/farmacologia , Pandemias , Ciclismo , Genes Bacterianos , China/epidemiologia , Resistência Microbiana a Medicamentos/genética , COVID-19/epidemiologia
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