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The Yellow River Delta possesses lots of characteristic medicinal plants due to its high salinity and high alkaline environment and Limonium sinense is an iconic plant. However, there are very few studies on L. sinense and its chemical constituents have not been investigated in recent ten years. In the present study, the chemical constituents and bioactivities of L. sinense were fully studied for the first time. UPLC-MS/MS method combined with database comparison identified 109 compounds mainly including flavonoids, alkaloids and polyphenols. In addition, the potential bioactivities of L. sinense were considerated as anti-inflammatory, anti-oxidative, anti-tumor, hepatoprotective and hpyerglycemic activities based on these identified compounds and their related literature. Furthermore, four derivatives of 12-oxo-phytodienoic acid and butenolide including two new ones (1 and 2) were isolated from the whole plants of L. sinense. Their structures, including the absolute configurations, were determined by the analysis of comprehensive spectroscopic data. All isolates were evaluated for their anti-inflammatory activity. Compound 1 exhibited moderate anti-inflammatory activity with IC50 value of 37.5 ± 1.2 µM on NO production level.

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To know the influence of lauric acid (LA) on wheat flour fresh noodles (WFN) quality and the latent mechanism, the effect of LA on cooking properties, digestibility and structure of WFN with/without sodium bicarbonate (SB) and the properties of wheat flour (WF) with/without SB were studied. The results indicated that LA reduced cooking loss and digestibility of WFN with SB and slightly decreased water adsorption and increased the free water binding ability and hardness of WFN without SB. Furthermore, LA increased the degree of short- and long-range order and molecular weight of starch in cooked WFN with/without SB and it had greater effect on the degree of short- and long-range order and molecular weight of starch in cooked WFN with SB than that without SB. Differential scanning calorimeter (DSC) and rapid viscosity analysis (RVA) displayed that WFN with LA and SB formed more starch-LA or/and starch-LA-protein complexes than WFN with LA. Additionally, the impact of LA on WFN quality and WF properties was influenced by SB concentration. This study will provide theoretical basis and new thoughts for the design of high-quality fresh noodles with low digestibility, low cooking loss and high hardness.

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Palmitoyl-protein thioesterase 1 (PPT1) is a lysosomal depalmitoylation enzyme that mediates protein posttranslational modifications. Loss-of-function mutation of PPT1 causes a failure of the lysosomal degradation of palmitoylated proteins and results in a congenital disease characterized by progressive neuronal degeneration referred to as infantile neuronal ceroid lipofuscinosis (INCL). A mouse knock-in model of PPT1 (PPT1-KI) was established by introducing the R151X mutation into exon 5 of the PPT1 gene, which exhibited INCL-like pathological lesions. We previously reported that hippocampal γ oscillations were impaired in PPT1 mice. Hippocampal γ oscillations can be enhanced by selective activation of the dopamine D4 receptor (DR4), a dopamine D2-like receptor. In this study, we investigated the changes in DR expression and the effects of dopamine and various DR agonists on neural network activity, cognition and motor function in PPT1KI mice. Cognition and motor defects were evaluated via Y-maze, novel object recognition and rotarod tests. Extracellular field potentials were elicited in hippocampal slices, and neuronal network oscillations in the gamma frequency band (γ oscillations) were induced by perfusion with kainic acid (200 nM). PPT1KI mice displayed progressive impairments in γ oscillations and hippocampus-related memory, as well as abnormal expression profiles of dopamine receptors with preserved expression of DR1 and 3, increased membrane expression of DR4 and decreased DR2 levels. The immunocytochemistry analysis revealed the colocalization of PPT1 with DR4 or DR2 in the soma and large dendrites of both WT and PPT1KI mice. Immunoprecipitation confirmed the interaction between PPT1 and DR4 or DR2. The impaired γ oscillations and cognitive functions were largely restored by the application of exogenous dopamine, the selective DR2 agonist quinpirole or the DR4 agonist A412997. Furthermore, the administration of A412997 (0.5 mg/kg, i.p.) significantly upregulated the activity of CaMKII in the hippocampus of 5-month-old PPT1KI mice. Collectively, these results suggest that the activation of D2-like dopamine receptors improves cognition and network activity in PPT1KI mice and that specific DR subunits may be potential targets for the intervention of neurodegenerative disorders, such as INCL.

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The poor prognosis of hepatocellular carcinoma (HCC) is still an urgent challenge to be solved worldwide. Hence, assembling drugs and targeted short peptides together to construct a novel medicine delivery strategy is crucial for targeted and synergy therapy of HCC. Herein, a high-efficiency nanomedicine delivery strategy has been constructed by combining graphdiyne oxide (GDYO) as a drug-loaded platform, specific peptide (SP94-PEG) as a spear to target HCC cells, sorafenib, doxorubicin-Fe2+ (DOX-Fe2+), and siRNA (SLC7A11-i) as weapons to exert a three-path synergistic attack against HCC cells. In this work, SP94-PEG and GDYO form nanosheets with HCC-targeting properties, the chemotherapeutic drug DOX linked to ferrous ions increases the free iron pool in HCC cells and synergizes with sorafenib to induce cell ferroptosis. As a key gene of ferroptosis, interference with the expression of SLC7A11 makes the ferroptosis effect in HCC cells easier, stronger, and more durable. Through gene interference, drug synergy, and short peptide targeting, the toxic side effects of chemotherapy drugs are reduced. The multifunctional nanomedicine GDYO@SP94/DOX-Fe2+/sorafenib/SLC7A11-i (MNMG) possesses the advantages of strong targeting, good stability, the ability to continuously induce tumor cell ferroptosis and has potential clinical application value, which is different from traditional drugs.

Asunto(s)

Carcinoma Hepatocelular , Doxorrubicina , Ferroptosis , Neoplasias Hepáticas , Nanomedicina , Péptidos , Sorafenib , Ferroptosis/efectos de los fármacos , Carcinoma Hepatocelular/tratamiento farmacológico , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Doxorrubicina/farmacología , Doxorrubicina/química , Nanomedicina/métodos , Sorafenib/farmacología , Sorafenib/química , Línea Celular Tumoral , Animales , Péptidos/química , Péptidos/farmacología , Ratones , Antineoplásicos/farmacología , Antineoplásicos/química , Sinergismo Farmacológico , Sistema de Transporte de Aminoácidos y+/metabolismo , Ratones Desnudos , ARN Interferente Pequeño , Ratones Endogámicos BALB C , Sistemas de Liberación de Medicamentos/métodos

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Two parallel pilot-scale reactors were operated to investigate pollutant removal performance and metabolic pathways in elemental sulfur-driven autotrophic denitrification (SDAD) process under low temperature and after addition of external electron donors. The results showed that low temperature slightly inhibited SDAD (average total nitrogen removal of ∼4.7 mg L-1) while supplement of sodium thiosulfate (stage 2) and sodium acetate (stage 3) enhanced denitrification and secretion of extracellular polymeric substances (EPS), leading to the average removal rate of 0.75 and 1.01 kg N m-3 d-1, respectively with over twice higher total EPS. Correspondingly, nitrogen and sulfur related microbial metabolisms especially nitrite reductase and nitric oxide reductase encoding were promoted by genera including Thermomonas and Thiobacillus. The variations revealed that extra sodium acetate improved denitrification and enriched more SDAD-related microorganisms compared with sodium thiosulfate, which potentially catalyzed the refinement of practical strategies for optimizing denitrification in low carbon to nitrogen ratio wastewater treatment.

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AIMS: 5 mC methylation and hydroxymethylation (5hmC) are associated with Alzheimer's disease (AD). However, previous studies were limited by the absence of a 5hmC calculation. This study aims to find AD associated predictors and potential therapeutic chemicals using bioinformatics approach integrating 5 mC, 5hmC, and expression changes, and an AD mouse model. METHODS: Gene expression microarray and 5 mC and 5hmC sequencing datasets were downloaded from GEO repository. 142 AD and 52 normal entorhinal cortex specimens were enrolled. Data from oxidative bisulfite sequencing (oxBS)-treated samples, which represent only 5 mC, were used to calculate 5hmC level. Functional analyses, random forest supervised classification and methylation validation were applied. Potential chemicals were predicted by CMap. Morris water maze, Y maze and novel object recognition behavior tests were performed using FAD4T AD mice model. Cortex and hippocampus tissues were isolated for immunohistochemical staining. RESULTS: C1QTNF5, UBD, ZFP106, NEDD1, AKT3, and MBP genes involving 13 promoter CpG sites with 5mc, 5hmC methylation and expression difference were identified. AKT3 and MBP were down-regulated in both patients and mouse model. Three CpG sites in AKT3 and MBP showed significant methylation difference on validation. FAD4T AD mice showed recession in brain functions and lower AKT3 expression in both cortex and hippocampus. Ten chemicals were predicted as potential treatments for AD. CONCLUSIONS: AKT3 and MBP may be associated with AD pathology and could serve as biomarkers. The ten predicted chemicals might offer new therapeutic approaches. Our findings could contribute to identifying novel markers and advancing the understanding of AD mechanisms.

Asunto(s)

Enfermedad de Alzheimer , Metilación de ADN , Proteínas Proto-Oncogénicas c-akt , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/genética , Animales , Ratones , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , 5-Metilcitosina/análogos & derivados , 5-Metilcitosina/metabolismo , Masculino , Modelos Animales de Enfermedad , Biomarcadores/metabolismo , Corteza Entorrinal/metabolismo , Corteza Entorrinal/patología , Femenino , Anciano , Hipocampo/metabolismo , Expresión Génica , Ratones Transgénicos

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Fluorinated liquid-crystal monomers (FLCMs) are a potential emerging class of persistent, bioaccumulative, and toxic compounds. Humans inevitably ingest FLCMs via food and the environment. However, there are limited studies on internal exposure biomonitoring of FLCMs. Herein, we evaluated the estimated daily intakes (EDIs) of FLCMs in the general population based on serum residue levels. For the first time, 38 FLCMs were detected in 314 serum samples from the general population in Beijing, with a median value of 132.48 ng/g of lipid weight (lw). BDPrB is a predominant FLCM in serum. The median EDI of ∑38FLCMs in the general residents was 37.96 pg/kg bw/day. The residual levels of most FLCMs were higher in urban than in suburban areas (p < 0.05). The concentrations of EFPEB, EDPrB, EDFPBB, and PDTFMTFT in serum showed positive associations with blood glucose (GLU) (r = 0.126-0.275, p < 0.05). Logistic regression analysis showed that FLCMs were significantly positively correlated with dyslipidemia, with an odds ratio of 2.19; BDPrB was significantly positively correlated with hyperglycemia (OR: 2.48). Overall, the present study suggests the occurrence of FLCMs in the nonoccupational population, and the exposure of certain FLCMs may cause abnormal blood glucose and lipid levels.

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Cristales Líquidos , Humanos , Femenino , Masculino , Persona de Mediana Edad

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OBJECTIVE: To investigate the association between a low oocyte maturity ratio from in vitro fertilization cycle and blastocyst euploidy. METHODS: A total of 563 preimplantation genetic testing (PGT) cycles (PGT cycles with chromosomal structural rearrangements were excluded) were performed between January 2021 and November 2022 at our center (average oocyte maturity rate: 86.4% ± 14.6%). Among them, 93 PGT cycles were classified into the low oocyte maturity rate group (group A, < mean - 1 standard deviation [SD]), and 186 PGT cycles were grouped into the average oocyte maturity rate group (group B, mean ± 1 SD). Group B was 2:1 matched with group A. Embryological, blastocyst ploidy, and clinical outcomes were compared between the two groups. RESULTS: The oocyte maturity (metaphase II [MII oocytes]), MII oocyte rate, and two pronuclei (2PN) rates were significantly lower in group A than in group B (5.2 ± 3.0 vs. 8.9 ± 5.0, P = 0.000; 61.6% vs. 93.0%, P = 0.000; 78.7% vs. 84.8%, P = 0.002, respectively). In group A, 106 of 236 blastocysts (44.9%) that underwent PGT for aneuploidy were euploid, which was not significantly different from the rate in group B (336/729, 46.1%, P = 0.753). However, euploid blastocysts were obtained only in 55 cycles in group A (55/93, 59.1%), which was lower than the rate in group B (145/186, 78.0%, P = 0.001). The clinical pregnancy rate in group B (73.9%) was higher than that in group A (58.0%) (P = 0.040). CONCLUSION: Our results suggest that a low oocyte maturity ratio is not associated with blastocyst euploidy but is associated with fewer cycles with euploid blastocysts for transfer, lower 2PN rates, and lower clinical pregnancy rates.

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BACKGROUND: The proposal of Q-markers for traditional Chinese medicine (TCM) represents a novel avenue of research pertaining to the quality control of TCM prescriptions. However, prior exploratory studies on Q-markers with multiple properties consistently neglected the consideration of weights, hampering our ability to accurately gauge the significance of each property and potentially leading to a flawed comprehension of Q-markers. PURPOSE: In this study, a quantitative ternary network strategy was firstly proposed to visually discover the Q-markers from TCM prescriptions, and it has been successfully applied into the quality control study of Bu-Zhong-Yi-Qi-Tang (BZYQT), a classical TCM prescription. METHODS: Firstly, the contents of 34 components in BZYQT, along with the kinetic features of 17 candidate Q-markers in biosamples (plasma and small intestinal contents), were characterized by UPLC-QqQ-MS/MS, and their immunomodulatory activities in macrophages and splenic lymphocytes were also assessed. Next, the obtained data were integrated into three properties: testability, bioavailability, effectiveness, and their weights were calculated using the entropy weight method to further establish a ternary network for quantitatively screening Q-markers. Subsequently, the identified Q-markers of BZYQT were utilized for the holistic quality evaluation of 36 batches of the commercial BZYQT preparation, Bu-Zhong-Yi-Qi-Pill (BZYQP) produced by three manufacturers, through similarity evaluation of the Q-marker-based fingerprint. RESULTS: Nine compounds (hesperidin, astragaloside IV, ononin, 18ß-glycyrrhizic acid, narirutin, calycosin, cimigenoside, astragaloside II, and liquiritin) showing three core properties, including testability, bioavailability, and effectiveness, were screened out as Q-markers of BZYQT based on their rankings in terms of regression area of the ternary network. Employing Q-markers as common peaks, the similarity values of 36 batches BZYQP ranged 0.914-0.998 under HPLC-UVD mode, and 0.631-1.000 under HPLC-ELSD mode, which were less than the similarity values evaluated by the conventional common peaks (HPLC-UVD mode: 0.946-0.990; HPLC-ELSD mode: 0.957-0.997). This observation suggests that the identified Q-markers are more representative as common peaks in chromatographic fingerprints for the holistic quality evaluation of TCM-related products from different manufacturers. CONCLUSION: The quantitative discovery of Q-markers from BZYQT laid an important foundation for holistic quality assessment of its related commercially available products, and our work offering a new strategy for ensuring the consistency and efficacy of TCM prescriptions.

Asunto(s)

Medicamentos Herbarios Chinos , Medicina Tradicional China , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/análisis , Animales , Cromatografía Líquida de Alta Presión/métodos , Control de Calidad , Espectrometría de Masas en Tándem/métodos , Masculino , Ratones

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Tumor growth and metastasis rely on angiogenesis. In recent years, long non-coding RNAs have been shown to play an important role in regulating tumor angiogenesis. Here, we review the multidimensional modes and relevant molecular mechanisms of long non-coding RNAs in regulating tumor angiogenesis. In addition, we summarize new strategies for tumor anti-angiogenesis therapies by targeting long non-coding RNAs. The aim of this study is to provide new diagnostic targets and treatment strategies for anti-angiogenic tumor therapy.

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Regulación Neoplásica de la Expresión Génica , Neoplasias , Neovascularización Patológica , ARN Largo no Codificante , ARN Largo no Codificante/genética , Humanos , Neovascularización Patológica/genética , Neoplasias/genética , Neoplasias/patología , Neoplasias/terapia , Neoplasias/irrigación sanguínea , Animales , Inhibidores de la Angiogénesis/uso terapéutico , Terapia Molecular Dirigida , Angiogénesis

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Various fascinating optical characteristics in organisms encourage scientists to develop biomimetic synthesis strategies and mimic their unique microstructure. Inspired by the Chameleon's skin with tunable color and superior flexibility, this work designs the evaporated-induced self-assembly technique to synthesize the chiral photonic crystal film. Ultrasonic-intensified and additive-assisted techniques synergistically optimize the film properties, on the aspects of optic and mechanic. The film shows considerable rigidity and superior flexibility, which can undergo multiple mechanical deformations. Without destroying the chiral nematic structure, the ultimate strain approaches 50%, which exceeds most cellulose-derived film materials. It also integrates excellent optical performance. The film color can cover the total visible region by tuning the photonic bandgap and has angle-dependent properties. It can make the response to humidity and solvents, and chromaticity variation reflects the degree of stimulation. Importantly, this structural-dependent color change is reversible. Lastly, the photonic crystal materials with excellent mechanics and unique optics have been applied in the security. The anti-counterfeiting material design contains photonic crystal ink, repeatable writing paper, information-hiding film, and color-changing labels, with the features of environmentally friendly, economical, non-destructive, and convenient for authentication.

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BACKGROUND: Physical activity (PA) is considered beneficial for lowering cardiovascular risks following type 2 diabetes mellitus (T2DM) and prediabetes, but existing evidence relies mainly on self-reported measurements. We aimed to describe the intensity-specific dose-response associations of PA and sedentary behavior (SB) with macrovascular and microvascular events among individuals with T2DM and prediabetes. METHODS: This study included 11,474 individuals with T2DM and prediabetes from the UK Biobank. PA, including total PA, moderate-to-vigorous intensity PA (MVPA), light intensity PA (LPA), and SB, were measured by accelerometers over 7 days. MVPA was categorized according to the American Diabetes Association guideline-recommended level (at least 150 min/week), and total PA, LPA, and SB were grouped by tertiles. The outcomes were incidences of macrovascular events, microvascular events, heart failure (HF), and their combination (composite events). The events were ascertained using the ICD-10 codes on the hospital or death records. RESULTS: During a median follow-up of 6.8 years, 1680 cases were documented, including 969 macrovascular events, 839 microvascular events, and 284 incidents of HF. Accelerometer-measured PA, irrespective of intensity, was inversely associated with the risk of composite events and each outcome in the dose-response patterns. Regarding categorized PA, engagement in total PA (high vs. low) was associated with decreased risk of macrovascular events (hazard ratio (HR) = 0.80; 95% confidence interval (95%CI): 0.67-0.95), microvascular events (HR = 0.76; 95%CI: 0.63-0.93), and HF (HR = 0.46; 95%CI: 0.32-0.66). Adherence to MVPA, but not LPA, above the guideline-recommended level (at least 150 min/week) was associated with reduced risk of macrovascular events (HR = 0.80; 95%CI: 0.68-0.95), microvascular events (HR = 0.76; 95%CI: 0.63-0.92), and HF (HR = 0.65; 95%CI: 0.46-0.92). The minimum dose of MVPA for lowering the risk of composite events was approximately 59.0 min/week. More time spent in SB was associated with an increased risk of composite events (high vs. low, HR = 1.17; 95%CI: 1.02-1.35) and HF (high vs. low, HR = 1.54; 95%CI: 1.09-2.20). Replacement of 30 min of SB (HR = 0.73; 95%CI: 0.65-0.81) and LPA (HR = 0.74; 95%CI: 0.66-0.83) with MVPA dramatically reduced the risk of composite events. CONCLUSION: Adherence to a higher amount of accelerometer-measured PA, especially MVPA at least 59 min/week, is associated with reduced risks of macrovascular and microvascular events among individuals with T2DM and prediabetes. Replacement of SB and LPA with MVPA helped lower the risk of diabetic vascular events.

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Protein-based subunit vaccines are weakly immunogenic, and developing self-adjuvanting vaccines with adjuvant conjugated to antigen is a promising approach for generating optimal immune responses. Here, we report a novel adjuvant-protein conjugate vaccine based on versatile oxime ligation technique. Firstly, the adjuvant properties of a series of TLR7 and TLR7/8 small molecule agonists in self-adjuvanting vaccines were systematically compared by coupling them to proteins in consistent ratio via p-carboxybenzaldehyde (p-CBA) for the first time. All conjugate vaccines induced cytokine secretion in murine and human macrophages in vitro, and promoted specific antibody production in vivo. Notably, a conjugate containing imidazoquinoline TLR7/8 agonist (TLR7/8a1) showed the greatest enhancement in Th1/2 balanced antibody response. To minimize the interference with the protein antigenic integrity, we further developed a systematic glycoconjugation strategy to conjugate this TLR7/8a1 onto the glycan chains of SARS-CoV-2 S1 glycoprotein via oxime ligation, in which S1 containing different numbers of aldehyde groups were obtained by differential periodate oxidation. The resulting TLR7/8a1-S1 conjugate triggered a potent humoral and cellular immunity in vivo. Together these data demonstrate the promise of these TLR7 and TLR7/8 agonists as effective built-in adjuvants, and the versatile oxime ligation strategy might broaden potential applications in designing different conjugate vaccines.

Asunto(s)

Adyuvantes Inmunológicos , Oximas , Receptor Toll-Like 7 , Receptor Toll-Like 8 , Receptor Toll-Like 7/agonistas , Receptor Toll-Like 7/inmunología , Receptor Toll-Like 8/agonistas , Receptor Toll-Like 8/inmunología , Animales , Oximas/química , Ratones , Humanos , Adyuvantes Inmunológicos/farmacología , Adyuvantes Inmunológicos/química , Femenino , SARS-CoV-2/inmunología , Vacunas Conjugadas/inmunología , Vacunas Conjugadas/química , Citocinas/metabolismo , COVID-19/prevención & control , COVID-19/inmunología , Macrófagos/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Vacunas de Subunidad/inmunología

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BACKGROUND: The self-repair ability after meniscal tears is poor, leading to the development of posttraumatic osteoarthritis. Promoting the repair of meniscal injuries remains a great challenge, especially in the avascular region. HYPOTHESIS: Local delivery of skeletal stem cell (SSC)-derived exosomes (SSC-Exos) would promote meniscal healing and prevent secondary osteoarthritis progression. STUDY DESIGN: Controlled laboratory study. METHODS: SSCs were isolated from bone marrow and exosomes were extracted via ultracentrifugation. The cell migration capabilities after incubation with exosomes were validated through in vitro cell culture. Full-thickness longitudinal medial meniscal tears were performed in the avascular region of 40 male Sprague-Dawley rats and 20 male New Zealand White rabbits, which were randomly divided into 2 groups: group treated with phosphate-buffered saline (GCON) and group treated with exosomes (GExosome). The effects of these treatments on meniscal healing and secondary osteoarthritis were evaluated by gross inspection, biomechanical testing, and histological assessment. RNA sequencing of in vitro cell cultures was performed to explore the underlying mechanisms. RESULTS: Exosomes were successfully extracted and identified. These exosomes significantly promoted cell migration capabilities in vitro (P < .01). The GExosome exhibited greater cell proliferation and tissue regeneration with type 2 collagen secretion, and a significantly higher meniscal repair score than that of the GCON at 8 weeks postoperatively (P < .05). In contrast to the degenerative changes in both the meniscus and articular cartilage of the GCON, meniscal tissue in the GExosome exhibited restoration of normal morphology with a smooth and glossy white surface and better mechanical strength at 8 weeks after meniscal repair. Both degeneration scores and synovitis scores were significantly higher in the GCON than in the GExosome (P < .05). Compared with the GCON, the expression of key genes related to cell migration, such as the chemokine family, was enhanced by exosome injection, leading to an upregulation of extracellular matrix expression while downregulating the expression of inflammation-related genes such as CD68 and the matrix metalloproteinase family. CONCLUSION: The administration of SSC-Exos effectively promoted meniscal healing in the avascular region and ameliorated secondary osteoarthritis. The effect might be attributed to inflammation modulation, promotion of cell migration, and secretion of extracellular matrix components. CLINICAL RELEVANCE: Injection of SSC-Exos represents a promising therapeutic option for promoting meniscal healing in the avascular region.

Asunto(s)

Exosomas , Ratas Sprague-Dawley , Lesiones de Menisco Tibial , Animales , Exosomas/trasplante , Conejos , Masculino , Lesiones de Menisco Tibial/terapia , Cicatrización de Heridas , Movimiento Celular , Osteoartritis/terapia , Ratas , Osteoartritis de la Rodilla/terapia , Células Madre , Proliferación Celular

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BACKGROUND: Gut microbiota dysbiosis induces intestinal barrier damage during parenteral nutrition (PN). However, the underlying mechanisms remain unclear. This study aimed to investigate gut microbiota dysbiosis, luminal short-chain fatty acids, and autophagy in a mouse model and how these short-chain fatty acids regulate autophagy. METHODS: Eight-week-old male specific-pathogen-free mice were randomly divided into a Chow group (standard diet and intravenous normal saline infusion) and a PN group (continuous infusion of PN nutrient solution) for 7 days. Caco-2 cells were also treated with intestinal rinse solutions from Chow and PN mouse models. RESULTS: Compared with the Chow group, the PN group exhibited increased Proteobacteria and decreased Firmicutes, correlating with decreased propyl acetate. In the PN group, intestinal tissue exhibited elevated adenosine monophosphate-activated protein kinase (AMPK) phosphorylation, LC3II protein levels, and Atg3 and Atg7 messenger RNA levels. P62 protein levels were decreased, indicating an increase of autophagy flux in the PN group. In the Caco-2 cell model, cells treated with PN solution plus propyl acetate exhibited increased Claudin-1 and occluding along with decreased interleukin-6 and tumor necrosis factor α compared with those treated with PN solution alone. Propyl acetate addition inhibited the AMPK-mammalian target of rapamycin (mTOR) pathway, mitigating the excessive autophagy induced by the PN intestinal rinse solution in Caco-2 cells. CONCLUSION: PN led to a significant reduction in propyl acetate levels in the intestine, excessive activation of autophagy, and barrier dysfunction. Propyl acetate inhibited excessive autophagy via the AMPK/mTOR signaling pathway and protected the intestinal barrier during PN.

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BACKGROUND AND AIMS: China is an endemic area for HEV infection. Estimating the prevalence and incidence of HEV infection in China plays a pivotal role in informing public health policies to prevent and control hepatitis E. This study aimed to investigate the prevalence of anti-HEV IgG and incidence of HEV seroconversion in China. METHODS: This study was based on the Meinian health check-up database in China. Participants who underwent testing for anti-HEV IgG at check-up centers in 24 provinces between 2017 and 2022 were included. In the cross-sectional analyses, overall prevalence and stratified prevalence in subpopulations with various characteristics were estimated and standardized according to the 2020 census of the Chinese population. In the longitudinal analyses, the occurrence of anti-HEV IgG positivity during the follow-up was defined as an incident HEV seroconversion. Overall and stratified incidence rates were estimated and expressed as per 100 person-years. Poisson regression was used to explore risk factors associated with HEV seroconversion. RESULTS: 85,238 and 11,154 participants were included in the cross-sectional and longitudinal analyses, respectively. The prevalence of anti-HEV IgG in the general population was 18.02%. During a median follow-up of 1.2 years, the incidence rate of HEV seroconversion was 1.79 per 100 person-years. Age ≥ 60 years, low socioeconomic status, living in coastal areas, living in areas with high drainage density, and living in areas with high anti-HEV IgG prevalence were independent risk factors for HEV seroconversion. CONCLUSIONS: Our findings would help inform policy making for hepatitis E prevention and control in China, as well as in other endemic regions of the world.

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Accumulating research suggested that long-term exposure to fine particulate matter (PM2.5) is related to cardiovascular disease (CVD). However, evidence regarding the relationship between PM2.5 and CVD risk factors remains inconsistent. We hypothesized that this association may be partially modified by socioeconomic status (SES). To investigate the relationships and to test the modifying effect of SES, we included baseline data for 21,018 adults from September 2017 to May 2018. PM2.5 concentrations were determined by employing an amalgamation of linear measurements obtained from monitoring stations located near the participants' residential and workplace addresses. We assessed SES across several domains, including income, education, and occupation levels, as well as through a composite SES index. The results indicated that for every 10 µg/m3 increase in PM2.5 exposure, the risk of hypercholesterolemia, hyperbetalipoproteinemia, diabetes, and hyperhomocysteinemia (HHcy) increased by 7.7% [Odds ratio (OR) = 1.077, 95% Confidence Interval (CI) = 1.011, 1.146], 19.6% (OR = 1.196, 95% CI = 1.091, 1.312), 4.2% (OR = 1.042, 95% CI = 1.002, 1.084), and 17.1% (OR = 1.171, 95% CI = 1.133, 1.209), respectively. Compared to the high SES group, those with low SES are more prone to hypercholesterolemia, hyperbetalipoproteinemia, diabetes, and HHcy. Notably, the disparities in SES appear significant in the relationship between PM2.5 exposure and hypercholesterolemia as well as hyperbetalipoproteinemia. But for diabetes and HHcy, the modification effect of SES on PM2.5 shows an inconsistent pattern. In conclusion, the results confirm the association between PM2.5 and cardiovascular risk factors and low SES significantly amplified the adverse PM2.5 effect on dyslipidemia. It is crucial to emphasize a need to improve the socioeconomic inequality among adults in Beijing and contribute to the understanding of the urgency in protecting the health of vulnerable groups.

Asunto(s)

Enfermedades Cardiovasculares , Exposición a Riesgos Ambientales , Factores de Riesgo de Enfermedad Cardiaca , Material Particulado , Clase Social , Humanos , Material Particulado/análisis , Masculino , Femenino , Estudios Transversales , Beijing/epidemiología , Persona de Mediana Edad , Enfermedades Cardiovasculares/epidemiología , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Adulto , Anciano , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/efectos adversos , Factores de Riesgo , Contaminación del Aire/efectos adversos

RESUMEN

OBJECTIVES: The aim of this study was to estimate the global burden, trends and health inequality of childhood nutritional deficiencies (CND) from 1990 to 2019. STUDY DESIGN: This was an epidemiological study. METHODS: Data were extracted from the 2019 Global Burden of Disease study. Estimates and 95% uncertainty intervals (UIs) for the rates and numbers were used to evaluate the global burden of CND. Temporal trends in the burden of CND were examined using Joinpoint analysis and average annual percentage changes. To assess health inequality, the slope index was used. RESULTS: In 2019, 52 million new cases of CND and 105,000 deaths related to CND were recorded. Additionally, 435 million prevalence cases and 26 million disability-adjusted life years (DALYs) were recorded in the same year. From 1990 to 2019, the incidence rate of CND generally increased globally, except for the years 2010-2017; conversely, the prevalence, death and DALY rates exhibited decreasing trends over the study period. Half of the analysed regions and countries/territories demonstrated decreasing trends in the incidence, prevalence, death and DALY rates associated with CND. The incidence and prevalence of CND remained high in low-middle sociodemographic index (SDI) and low-SDI regions; however, they exhibited decreasing trends over the 30-year study period. The slope indexes showed that there were no significant changes in SDI-related inequality over 30 years. CONCLUSIONS: Despite decreasing trends in the prevalence, death and DALY rates associated with CND over the three decades, the degree of inequality related to SDI in the burden of nutritional deficiencies has not shown a significant decline. In summary, CND remain a major public health burden in middle-SDI and low-SDI countries.

Asunto(s)

Trastornos de la Nutrición del Niño , Años de Vida Ajustados por Discapacidad , Carga Global de Enfermedades , Salud Global , Humanos , Salud Global/estadística & datos numéricos , Carga Global de Enfermedades/tendencias , Preescolar , Lactante , Niño , Prevalencia , Trastornos de la Nutrición del Niño/epidemiología , Incidencia , Masculino , Disparidades en el Estado de Salud , Femenino

RESUMEN

Introduction: As robot teleoperation increasingly becomes integral in executing tasks in distant, hazardous, or inaccessible environments, operational delays remain a significant obstacle. These delays, inherent in signal transmission and processing, adversely affect operator performance, particularly in tasks requiring precision and timeliness. While current research has made strides in mitigating these delays through advanced control strategies and training methods, a crucial gap persists in understanding the neurofunctional impacts of these delays and the efficacy of countermeasures from a cognitive perspective. Methods: This study addresses the gap by leveraging functional Near-Infrared Spectroscopy (fNIRS) to examine the neurofunctional implications of simulated haptic feedback on cognitive activity and motor coordination under delayed conditions. In a human-subject experiment (N = 41), sensory feedback was manipulated to observe its influences on various brain regions of interest (ROIs) during teleoperation tasks. The fNIRS data provided a detailed assessment of cerebral activity, particularly in ROIs implicated in time perception and the execution of precise movements. Results: Our results reveal that the anchoring condition, which provided immediate simulated haptic feedback with a delayed visual cue, significantly optimized neural functions related to time perception and motor coordination. This condition also improved motor performance compared to the asynchronous condition, where visual and haptic feedback were misaligned. Discussion: These findings provide empirical evidence about the neurofunctional basis of the enhanced motor performance with simulated synthetic force feedback in the presence of teleoperation delays. The study highlights the potential for immediate haptic feedback to mitigate the adverse effects of operational delays, thereby improving the efficacy of teleoperation in critical applications.