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1.
Poult Sci ; 103(6): 103715, 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38652954

RESUMO

Eggshell is one of the most important indicators of egg quality, and due to low shell strength, pimple eggs (PE) are more susceptible to breakage, thus causing huge economic losses to the egg industry. At the current time, the molecular mechanisms that regulate the formation of pimple eggs are poorly understood. In this study, uterine tissues of PE-laying hens (n = 8) and normal egg (NE) -laying hens (n = 8) were analyzed by whole transcriptome sequencing, and a total of 619 differentially expressed mRNAs (DE mRNAs), 122 differentially expressed lncRNAs (DE lncRNAs) and 21 differentially expressed miRNAs (DE miRNAs) were obtained. Based on the targeting relationship among DE mRNAs, DE lncRNAs and DE miRNAs, we constructed a competitive endogenous RNA (ceRNA) network including 12 DE miRNAs, 19 DE lncRNAs, and 128 DE mRNAs. Considering the large amount of information contained in the network, we constructed a smaller ceRNA network to better understand the complex mechanisms of pimple egg formation. The smaller ceRNA network network contains 7 DE lncRNAs (LOC107056551, LOC121109367, LOC121108909, LOC121108862, LOC112530033, LOC121113165, LOC107054145), 5 DE miRNAs (gga-miR-6568-3p, gga-miR-31-5p, gga-miR-18b-3p, gga-miR-1759-3p, gga-miR-12240-3p) and 7 DE mRNAs (CABP1, DNAJC5, HCN3, HPCA, IBSP, KCNT1, OTOP3), and these differentially expressed genes may play key regulatory roles in the formation of pimpled eggs in hens. This study provides the overall expression profiles of mRNAs, lncRNAs and miRNAs in the uterine tissues of hens, which provides a theoretical basis for further research on the molecular mechanisms of pimpled egg formation, and has potential applications in improving eggshell quality.

2.
Gut Microbes ; 16(1): 2334967, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38630006

RESUMO

Human milk oligosaccharides (HMOs) are vital milk carbohydrates that help promote the microbiota-dependent growth and immunity of infants. Sialic acid (SA) is a crucial component of sialylated milk oligosaccharides (S-MOs); however, the effects of SA supplementation in lactating mothers on S-MO biosynthesis and their breastfed infants are unknown. Probiotic intervention during pregnancy or lactation demonstrates promise for modulating the milk glycobiome. Here, we evaluated whether SA and a probiotic (Pro) mixture could increase S-MO synthesis in lactating mothers and promote the microbiota development of their breastfed neonates. The results showed that SA+Pro intervention modulated the gut microbiota and 6'-SL contents in milk of maternal rats more than the SA intervention, which promoted Lactobacillus reuteri colonization in neonates and immune development. Deficient 6'-SL in the maternal rat milk of St6gal1 knockouts (St6gal1-/-) disturbed intestinal microbial structures in their offspring, thereby impeding immune tolerance development. SA+Pro intervention in lactating St6gal1± rats compromised the allergic responses of neonates by promoting 6'-SL synthesis and the neonatal gut microbiota. Our findings from human mammary epithelial cells (MCF-10A) indicated that the GPR41-PI3K-Akt-PPAR pathway helped regulate 6'-SL synthesis in mammary glands after SA+Pro intervention through the gut - breast axis. We further validated our findings using a human-cohort study, confirming that providing SA+Pro to lactating Chinese mothers increased S-MO contents in their breast milk and promoted gut Bifidobacterium spp. and Lactobacillus spp. colonization in infants, which may help enhance immune responses. Collectively, our findings may help alter the routine supplementation practices of lactating mothers to modulate milk HMOs and promote the development of early-life gut microbiota and immunity.


Assuntos
Microbioma Gastrointestinal , Ácido N-Acetilneuramínico , Feminino , Lactente , Gravidez , Humanos , Animais , Ratos , Lactação , Estudos de Coortes , Fosfatidilinositol 3-Quinases , Leite Humano , Imunidade
3.
J Environ Sci (China) ; 142: 11-20, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38527877

RESUMO

Chromium released during municipal solid waste incineration (MSWI) is toxic and carcinogenic. The removal of chromium from simulated MSWI flue gas by four sorbents (CaO, bamboo charcoal (BC), powdered activated carbon (PAC), and Al2O3) and the effects of four oxides (SiO2, Al2O3, Fe2O3, and CaO) on chromium speciation transformation were investigated. The results showed that the removal rates of total Cr by the four sorbents were Al2O3 < CaO < PAC < BC, while the removal rates of Cr(VI) by the four sorbents were Al2O3 < PAC < BC < CaO. CaO had a strong oxidizing effect on Cr(III), while BC and PAC had a better-reducing effect on Cr(VI). SiO2 was better for the reduction of Na2CrO4 and K2CrO4 above 1000°C due to its strong acidity, and the addition of CaO significantly inhibited the reduction of Cr(VI). MgCrO4 decomposed above 700°C to form MgCr2O4, and the reaction between MgCrO4 and oxides also existed in the form of a more stable trivalent spinel. Furthermore, when investigating the effect of oxides on the oxidation of Cr(III) in CrCl3, it was discovered that CaO promoted the conversion of Cr(III) to Cr(VI), while the presence of chlorine caused chromium to exist in the form of Cr(V), and increasing the content of CaO and extending the heating time facilitated the oxidation of Cr(III). In addition, silicate, aluminate, and ferrite were generated after the addition of SiO2, Al2O3, and Fe2O3, which reduced the alkalinity of CaO and had an important role in inhibiting the oxidation of Cr(III). The acidic oxides can not only promote the reduction of Cr(VI) but also have an inhibitory effect on the oxidation of Cr(III) ascribed to alkali metals/alkaline earth metals, and the proportion of acidic oxides can be increased moderately to reduce the generation of harmful substances in the hazardous solid waste heat treatment.


Assuntos
Óxidos , Resíduos Sólidos , Dióxido de Silício , Cromo/análise , Oxirredução , Incineração
4.
Sci Rep ; 14(1): 7382, 2024 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-38548813

RESUMO

The structural characteristics of plant communities in urban green spaces have a significant impact on their carbon sequestration function. In this study, comprehensive data were collected from 106 plant communities (each 20 m × 20 m) in Zhengzhou Green Expo Park. We assessed aboveground and soil carbon storage, alongside maintenance carbon emissions, to quantify carbon dynamics. Our primary objective was to establish a statistical model that correlates the structural attributes of plant communities with their total annual carbon sequestration. This model aims to provide a quantitative framework for optimizing community structures to maximize carbon sequestration in urban green spaces. The results showed that density and coverage were significantly and positively correlated with aboveground and soil carbon stocks. Density and mean height were significantly and positively correlated with maintenance carbon emissions. Density played a key structural role in regulating the total carbon sequestration of the plant communities, being 27.24 times more effective than coverage. The total annual carbon sequestration of the plant community reached an optimal value of 327.67 kg CO2-eq/y-1 at a density and cover of 0.15 and 1, respectively. This study provides valuable data for increasing the carbon sink ability of urban green spaces through plant structure regulation and supporting low-carbon development strategies in urban management.


Assuntos
Sequestro de Carbono , Parques Recreativos , Plantas , Carbono , Solo/química
5.
Leukemia ; 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38402368

RESUMO

Iron metabolism plays a crucial role in cell viability, but its relationship with adult stem cells and cancer stem cells is not fully understood. The ferritin complex, responsible for intracellular iron storage, is important in this process. We report that conditional deletion of ferritin heavy chain 1 (Fth1) in the hematopoietic system reduced the number and repopulation capacity of hematopoietic stem cells (HSCs). These effects were associated with a decrease in cellular iron level, leading to impaired mitochondrial function and the initiation of apoptosis. Iron supplementation, antioxidant, and apoptosis inhibitors reversed the reduced cell viability of Fth1-deleted hematopoietic stem and progenitor cells (HSPCs). Importantly, leukemic stem cells (LSCs) derived from MLL-AF9-induced acute myeloid leukemia (AML) mice exhibited reduced Fth1 expression, rendering them more susceptible to apoptosis induced by the iron chelation compared to normal HSPCs. Modulating FTH1 expression using mono-methyl fumarate increased LSCs resistance to iron chelator-induced apoptosis. Additionally, iron supplementation, antioxidant, and apoptosis inhibitors protected LSCs from iron chelator-induced cell death. Fth1 deletion also extended the survival of AML mice. These findings unveil a novel mechanism by which ferritin-mediated iron homeostasis regulates the survival of both HSCs and LSCs, suggesting potential therapeutic strategies for blood cancer with iron dysregulation.

6.
Biology (Basel) ; 13(1)2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38275732

RESUMO

The decline of Japanese eel (Anguilla japonica) populations in the Yangtze River estuary represents a critical conservation concern. Eleven-years of daily catch data during recruitment periods (i.e., January-April, 2012-2022) indicate that annual catch averaged from 153 to 1108 eels, and show a bimodal pattern in glass eel arrivals. Utilizing seasonal-trend decomposition and generalized additive models, we demonstrated a strong correlation between catch abundance, optimal water temperatures, and lunar cycles. An auto-regressive integrated moving average (ARIMA) model predicts an increase in glass eel numbers for 2023-2024 but also points to a concerning trend of delayed recruitment timing since 2016, attributable to the 0.48 °C per decade rise in sea surface temperatures. This delay correlates with a significant decrease in the average body weight of glass eels, suggesting potential energy deficits that may hinder successful upstream migration. This study not only furthers our understanding of glass eel recruitment dynamics but also underscores the urgent need for targeted conservation measures. Additionally, it highlights the importance of sustained, detailed monitoring to mitigate the detrimental effects of climate change on these eels, vital for preserving the Yangtze River's ecological integrity.

7.
Fitoterapia ; 172: 105730, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37939738

RESUMO

Diabetic gastroparesis (DGP) is a common complication of type 2 diabetes mellitus (T2DM). Alpinia officinarum Hance (AOH) is one of the most commonly used both as a food and folk medicines, which is rich in diarylheptanoids and flavonoids. The gastroprotection and hypoglycemic effect make AOH has great potential in developing of anti-DGP complementary medicine. However, the molecular mechanisms of AOH that act against DGP are yet to be elucidated. In this study, we evaluated the therapeutic effects, the potential molecular mechanism, and the changes of gut microbiota of AOH in DGP. The 5 components of the AOH were analyzed, and the potential signaling pathway of AOH improving DGP was predicted by molecular docking. Subsequently, DGP rat model was constructed using high-fat-irregular-diet, AOH intervention significantly reduced blood glucose levels, increased gastrointestinal propulsion rate, and improved gastric histological morphology in DGP rats. Meanwhile, AOH has been shown to regulate the SCF/c-kit signaling pathway and rebalance the gut microbiota, which may be closely related to its role in improving DGP. Taken together, AOH may play a protective role on DGP through multiple mechanisms, which might pave the road for development and utilization of AOH.


Assuntos
Alpinia , Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Gastroparesia , Ratos , Animais , Gastroparesia/tratamento farmacológico , Gastroparesia/etiologia , Gastroparesia/metabolismo , Ratos Sprague-Dawley , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Simulação de Acoplamento Molecular , Estrutura Molecular , Transdução de Sinais
8.
Int J Biol Macromol ; 254(Pt 2): 127845, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37935292

RESUMO

Targeting SHP2 has become a potential cancer treatment strategy. In this study, ellagic acid was first reported as a competitive inhibitor of SHP2, with an IC50 value of 0.69 ± 0.07 µM, and its inhibitory potency was 34.86 times higher that of the positive control NSC87877. Ellagic acid also had high inhibitory activity on the SHP2-E76K and SHP2-E76A mutants, with the IC50 values of 1.55 ± 0.17 µM and 0.39 ± 0.05 µM, respectively. Besides, the IC50 values of ellagic acid on homologous proteins SHP1, PTP1B, and TCPTP were 0.93 ± 0.08 µM, 2.04 ± 0.28 µM, and 11.79 ± 0.83 µM, with selectivity of 1.35, 2.96, and 17.09 times, respectively. The CCK8 proliferation experiment exhibited that ellagic acid would inhibit the proliferation of various cancer cells. It was worth noting that the combination of ellagic acid and KRASG12C inhibitor AMG510 would produce a strong synergistic effect in inhibiting NCI-H358 cells. Western blot experiment exhibited that ellagic acid would downregulate the phosphorylation levels of Erk and Akt in NCI-H358 and MDA-MB-468 cells. Molecular docking and molecular dynamics studies revealed the binding information between SHP2 and ellagic acid. In summary, this study provides new ideas for the development of SHP2 inhibitors.


Assuntos
Ácido Elágico , Neoplasias , Humanos , Ácido Elágico/farmacologia , Simulação de Acoplamento Molecular , Neoplasias/tratamento farmacológico , Inibidores Enzimáticos/química , Fosforilação
9.
Mar Environ Res ; 194: 106299, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38154196

RESUMO

Noise pollution is increasingly prevalent in aquatic ecosystems, causing detrimental effects on growth and behavior of marine fishes. The physiological responses of fish to underwater noise are poorly understood. In this study, we used RNA-sequencing (RNA-seq) to study the transcriptome of the sonic muscle in small yellow croaker (Larimichthys polyactis) after exposure to a 120 dB noise for 30 min. The behavioral experiment revealed that noise exposure resulted in accelerated tail swimming behavior at the beginning of the exposure period, followed by loss of balance at the end of experiment. Transcriptomic analysis found that most highly expressed genes in the sonic muscle, including parvalbumin, slc25a4, and troponin C were related with energy metabolism and locomotor function. Further, a total of 1261 differentially expressed genes (DEGs) were identified, including 284 up-regulated and 977 down-regulated genes in the noise exposure group compared with the control group. Gene ontology (GO) analysis indicated that the most enriched categories of DEGs included protein folding and response to unfolding protein. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis found over-represented pathways including protein processing in the endoplasmic reticulum, chaperones and folding catalysts, as well as arginine and proline metabolism. Specifically, many genes related to fatty acid and collagen metabolism were up-regulated in the noise exposure group. Taken together, our results indicate that exposure to noise stressors alters the swimming behavior of croaker, inducing endoplasmic reticulum stress, disrupting lipid metabolism, and causing collagen degradation in the sonic muscle of L. polyactis.


Assuntos
Ecossistema , Perciformes , Animais , Perfilação da Expressão Gênica/métodos , Transcriptoma , Músculos , Perciformes/genética , Colágeno/genética
10.
ACS Appl Eng Mater ; 1(10): 2745-2751, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37927948

RESUMO

Passive water transport by taking advantage of capillary forces is vital for various applications such as solar-driven interfacial evaporation, evaporative cooling, and atmospheric water harvesting. Surface engineering and structure design with a hydrophilic surface and enhanced capillary force will facilitate passive water transport. Herein, we demonstrate a hydrophilic Cu/CuO foil-based roll for accelerated water transportation. The roll was fabricated by rolling up a typical 2D Cu/CuO film, which transforms the water climbing behavior by significantly enhancing the capillary force between each Cu/CuO film layer. The simple spatial transformation for a 2D film, from planar foil to 3D structure, has extensively facilitated water transportation performance and broadened its practical application potential. The Cu/CuO film with a blade-like nanostructure and excellent hydrophilicity ensures water supply to a limited area, while the capillary effect between different layers of the Cu/CuO foil extends the water transportation height. Consequently, the Cu/CuO foil-based roll demonstrated a high fluidic transport velocity. This design derived from the 2D planar film can be potentially employed for a large range of applications such as evaporating in a confined space and evaporation-driven energy harvest.

11.
Opt Express ; 31(16): 26757-26763, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37710527

RESUMO

A single-frequency quasi-continuous-wave partially end-pumped slab (Innoslab) laser amplifier at 1319 nm was demonstrated. The 3-W single-frequency all-fiber seed laser was amplified to a maximum average power of 80.1 W and the power stability was 0.52% in 10 minutes. The corresponding optical-optical efficiency was 16.1% under absorbed pump power of 478 W. The output pulse width was 131 µs at the repetition of 500 Hz. The beam quality factors of M2 were 1.3 in both the vertical and horizontal directions. To the best of our knowledge, this is the first report on single-frequency Nd:YAG Innoslab amplifier at 1319 nm with such high output power and efficiency.

12.
Front Biosci (Landmark Ed) ; 28(8): 164, 2023 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-37664921

RESUMO

BACKGROUND: Alpinia officinarum Hance (AOH) has a long history in China as a Chinese medicine and exerts the pharmacological effects of antidiabetic and gastrointestinal protection. In traditional Chinese medicine theory, AOH is often combined with other Chinese medicines for the treatment of diabetic gastroparesis (DGP). However, the molecular mechanisms, potential targets, and bioactive ingredients of AOH that act against DGP are yet to be elucidated. In this study, network pharmacology, molecular docking, and experimental study were used to predict the therapeutic effects and the potential molecular mechanism of AOH in DGP. METHODS: Network pharmacology analysis was performed to acquire information on the active chemical ingredients, DGP-related target proteins in AOH, and potential signaling pathway. In addition, molecular docking approach was used to simulate the binding of drugs and targets. Finally, DGP-mice model was used for experimental verification in vivo. Results: Through the network pharmacological research, AKT1 was found to be the core protein in AOH for the treatment of DGP and was mainly involved in the PI3K-AKT signaling pathway. Additionally, the interactions between bioactive compounds and target proteins (PIK3CA and AKT1) were analyzed using molecular docking, which verified the results of network pharmacology. Further in vivo studies indicated that AOH could reduce fasting blood glucose levels, improve gastric emptying rate, and ameliorate biochemical indicators in DGP mice. Moreover, AOH could increase the expressions and phosphorylation levels of PI3K and AKT in the stomach to regulate oxidative stress. CONCLUSIONS: The study has shown that AOH may play a protective role on DGP through mediation of the PI3K-AKT signaling pathway to regulate oxidative stress.


Assuntos
Alpinia , Diabetes Mellitus , Gastroparesia , Animais , Camundongos , Gastroparesia/tratamento farmacológico , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt
13.
BMJ Open ; 13(9): e073332, 2023 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-37669845

RESUMO

OBJECTIVES: Human papillomavirus (HPV) infection is closely associated with cervical cancer, especially the persistent infection of high-risk HPV (HR-HPV) genotypes. Therefore, investigating the HPV prevalence, age-specific, genotype distribution and the impact of the COVID-19 pandemic among large populations was essential for HPV screening and optimising vaccination. DESIGN: This was a cross-sectional study. METHODS: A total of 38 056 cervical epithelial cell specimens were collected in Weifang city from January 2018 to December 2022. The study was divided into seven age groups based on the age of the participants. HPV genotype testing was performed by using a commercial kit which is designed for the detection of 23 HPV genotypes. RESULT: A total of 8998 women were infected with HPV, with an overall positive rate of 23.64% (8998/38 056). Single infection of HPV was dominant among different age groups, which accounted for 71.33% of total infections. The most prevalent genotype was HR-HPV 16 (4.33%), followed by 52, 58, 53 and 68. Low-risk HPV (LR-HPV) 42 exhibited the highest prevalence (2.19%) among six LR-HPV genotypes, representing a novel finding. There was a significant difference in the prevalence across different age groups (p<0.01), with the highest prevalence in the group under 25 years old. During the 3 year COVID-19 breakout period, the number of HPV samples received in 2020, 2021 and 2022 was reduced by 24.03%, 14.79% and 24.76%, respectively. In 2018-2022, the annual prevalence varied between 21.09% and 25.30%, with a decreasing trend, while the prevalence of HR-HPV 39, 56, 31 and LR-HPV 42 increased. CONCLUSION: This study indicates a high-HPV infection rate and age-specific distribution characteristics of HPV genotype infections, as well as analyses of the impact of the COVID-19 outbreak on the HPV prevalence, which provides an epidemiological basis for the control and prevention of HPV infection in this region.


Assuntos
COVID-19 , Infecções por Papillomavirus , Humanos , Feminino , Adulto , Estudos Transversais , Pandemias , Prevalência , China , Genótipo , Papillomaviridae
14.
Gut Microbes ; 15(2): 2247025, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37614109

RESUMO

Synbiotics are increasingly used by the general population to boost immunity. However, there is limited evidence concerning the immunomodulatory effects of synbiotics in healthy individuals. Therefore, we conducted a double-blind, randomized, placebo-controlled study in 106 healthy adults. Participants were randomly assigned to receive either synbiotics (containing Bifidobacterium lactis HN019 1.5 × 108 CFU/d, Lactobacillus rhamnosus HN001 7.5 × 107 CFU/d, and fructooligosaccharide 500 mg/d) or placebo for 8 weeks. Immune parameters and gut microbiota composition were measured at baseline, mid, and end of the study. Compared to the placebo group, participants receiving synbiotic supplementation exhibited greater reductions in plasma C-reactive protein (P = 0.088) and interferon-gamma (P = 0.008), along with larger increases in plasma interleukin (IL)-10 (P = 0.008) and stool secretory IgA (sIgA) (P = 0.014). Additionally, synbiotic supplementation led to an enrichment of beneficial bacteria (Clostridium_sensu_stricto_1, Lactobacillus, Bifidobacterium, and Collinsella) and several functional pathways related to amino acids and short-chain fatty acids biosynthesis, whereas reduced potential pro-inflammatory Parabacteroides compared to baseline. Importantly, alternations in anti-inflammatory markers (IL-10 and sIgA) were significantly correlated with microbial variations triggered by synbiotic supplementation. Stratification of participants into two enterotypes based on pre-treatment Prevotella-to-Bacteroides (P/B) ratio revealed a more favorable effect of synbiotic supplements in individuals with a higher P/B ratio. In conclusion, this study suggested the beneficial effects of synbiotic supplementation on immune parameters, which were correlated with synbiotics-induced microbial changes and modified by microbial enterotypes. These findings provided direct evidence supporting the personalized supplementation of synbiotics for immunomodulation.


Assuntos
Actinobacteria , Microbioma Gastrointestinal , Simbióticos , Humanos , Adulto , Aminoácidos , Bacteroides
15.
Cancers (Basel) ; 15(14)2023 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-37509405

RESUMO

Non-alcoholic steatohepatitis (NASH), which is the most severe manifestation of non-alcoholic fatty liver disease (NAFLD), has been recognized as a major hepatocellular carcinoma (HCC) catalyst. However, the molecular mechanism of NASH-liver fibrosis-HCC sequence remains unclear and a specific and effective treatment for NASH has not yet been established. The progress in this field depends on the availability of reliable preclinical models which show the steady progression to NASH, liver cirrhosis, and HCC. However, most of the NASH mouse models that have been described to date develop NASH generally for more than 24 weeks and there is an uncertainty of HCC development. To overcome such shortcomings of experimental NASH studies, we established a novel NASH-HCC mouse model with very high reproducibility, generality, and convenience. We treated male C57BL/6J mice with a newly developed choline-deficient and methionine-restricted high-fat diet, named OYC-NASH2 diet, for 60 weeks. Treatment of OYC-NASH2 diet for 3 weeks revealed marked steatosis, lobular inflammation, and fibrosis, histologically diagnosed as NASH. Liver cirrhosis was observed in all mice with 48-week treatment. Liver nodules emerged at 12 weeks of the treatment, > 2 mm diameter liver tumors developed in all mice at 24 weeks of the treatment and HCC appeared after 36-week treatment. In conclusion, our rapidly progressive and highly reproducible NASH-liver cirrhosis-HCC model is helpful for preclinical development and research on the pathogenesis of human NAFLD-NASH-HCC. Our mouse model would be useful for the development of novel chemicals for NASH-HCC-targeted therapies.

16.
Acta Biomater ; 168: 515-528, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37433359

RESUMO

l-Ornithine (Orn) is a core amino acid responsible for ammonia detoxification in the body via the hepatic urea cycle. Clinical studies in Orn therapy have focused on interventions for hyperammonemia-associated diseases, such as hepatic encephalopathy (HE), a life-threatening neurological symptom affecting more than 80% of patients with liver cirrhosis. However, its low molecular weight (LMW) causes Orn to diffuse nonspecifically and be rapidly eliminated from the body after oral administration, resulting in unfavorable therapeutic efficacy. Hence, Orn is constantly supplied by intravenous infusion in many clinical settings; however, this treatment inevitably decreases patient compliance and limits its application in long-term management. To improve the performance of Orn, we designed self-assembling polyOrn-based nanoparticles for oral administration through ring-opening polymerization of Orn-N-carboxy anhydride initiated with amino-ended poly(ethylene glycol), followed by acylation of free amino groups in the main chain of the polyOrn segment. The obtained amphiphilic block copolymers, poly(ethylene glycol)-block-polyOrn(acyl) (PEG-block-POrn(acyl)), enabled the formation of stable nanoparticles (NanoOrn(acyl)) in aqueous media. We employed the isobutyryl (iBu) group for acyl derivatization in this study (NanoOrn(iBu)). In the healthy mice, daily oral administration of NanoOrn(iBu) for one week did not induce any abnormalities. In the mice exhibiting acetaminophen (APAP)-induced acute liver injury, oral pretreatment with NanoOrn(iBu) effectively reduced systemic ammonia and transaminases levels compared to the LMW Orn and untreated groups. The results suggest that the application of NanoOrn(iBu) is of significant clinical value with the feasibility of oral delivery and improvement in APAP-induced hepatic pathogenesis. STATEMENT OF SIGNIFICANCE: Liver injury is often accompanied by hyperammonemia, a life-threatening condition characterized by elevated blood ammonia levels. Current clinical treatments for reducing ammonia typically entail the invasive approach of intravenous infusion, involving the administration of l-ornithine (Orn) or a combination of Orn and L-aspartate. This method is employed due to the poor pharmacokinetics associated with these compounds. In our pursuit of enhancing therapy, we have developed an orally administrable nanomedicine based on Orn-based self-assembling nanoparticle (NanoOrn(iBu)), which provides sustained Orn supply to the injured liver. Oral administration of NanoOrn(iBu) to healthy mice did not cause any toxic effects. In a mouse model of acetaminophen-induced acute liver injury, oral administration of NanoOrn(iBu) surpassed Orn in reducing systemic ammonia levels and liver damage, thereby establishing NanoOrn(iBu) as a safe and effective therapeutic option.


Assuntos
Hiperamonemia , Camundongos , Animais , Hiperamonemia/induzido quimicamente , Hiperamonemia/complicações , Hiperamonemia/tratamento farmacológico , Ornitina/farmacologia , Ornitina/uso terapêutico , Ornitina/metabolismo , Acetaminofen/farmacologia , Polímeros/farmacologia , Amônia/metabolismo , Amônia/farmacologia , Nanomedicina , Fígado , Polietilenoglicóis/farmacologia
17.
Nat Commun ; 14(1): 4590, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37524697

RESUMO

Optical chaos is vital for various applications such as private communication, encryption, anti-interference sensing, and reinforcement learning. Chaotic microcombs have emerged as promising sources for generating massive optical chaos. However, their inter-channel correlation behavior remains elusive, limiting their potential for on-chip parallel chaotic systems with high throughput. In this study, we present massively parallel chaos based on chaotic microcombs and high-nonlinearity AlGaAsOI platforms. We demonstrate the feasibility of generating parallel chaotic signals with inter-channel correlation <0.04 and a high random number generation rate of 3.84 Tbps. We further show the application of our approach by demonstrating a 15-channel integrated random bit generator with a 20 Gbps channel rate using silicon photonic chips. Additionally, we achieved a scalable decision-making accelerator for up to 256-armed bandit problems. Our work opens new possibilities for chaos-based information processing systems using integrated photonics, and potentially can revolutionize the current architecture of communication, sensing and computations.

18.
Sensors (Basel) ; 23(14)2023 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-37514610

RESUMO

Compared to wide-field telescopes, small-field detection systems have higher spatial resolution, resulting in stronger detection capabilities and higher positioning accuracy. When detecting by small fields in synchronous orbit, both space debris and fixed stars are imaged as point targets, making it difficult to distinguish them. In addition, with the improvement in detection capabilities, the number of stars in the background rapidly increases, which puts higher requirements on recognition algorithms. Therefore, star detection is indispensable for identifying and locating space debris in complex backgrounds. To address these difficulties, this paper proposes a real-time star extraction method based on adaptive filtering and multi-frame projection. We use bad point repair and background suppression algorithms to preprocess star images. Afterwards, we analyze and enhance the target signal-to-noise ratio (SNR). Then, we use multi-frame projection to fuse information. Subsequently, adaptive filtering, adaptive morphology, and adaptive median filtering algorithms are proposed to detect trajectories. Finally, the projection is released to locate the target. Our recognition algorithm has been verified by real star images, and the images were captured using small-field telescopes. The experimental results demonstrate the effectiveness of the algorithm proposed in this paper. We successfully extracted hip-27066 star, which has a magnitude of about 12 and an SNR of about 1.5. Compared with existing methods, our algorithm has advantages in both recognition rate and false-alarm rate, and can be used as a real-time target recognition algorithm for space-based synchronous orbit detection payloads.

19.
J Dairy Sci ; 106(8): 5253-5265, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37414601

RESUMO

Whey protein powder (PP), which is mainly derived from bovine milk, is rich in milk fat globule membrane (MFGM). The MGFM has been shown to play a role in promoting neuronal development and cognition in the infant brain. However, its role in Alzheimer's disease (AD) has not been elucidated. Here, we showed that the cognitive ability of 3×Tg-AD mice (a triple-transgenic mouse model of AD) could be improved by feeding PP to mice for 3 mo. In addition, PP ameliorated amyloid peptide deposition and tau hyperphosphorylation in the brains of AD mice. We found that PP could alleviate AD pathology by inhibiting neuroinflammation through the peroxisome proliferator-activated receptor γ (PPARγ)-nuclear factor-κB signaling pathway in the brains of AD mice. Our study revealed an unexpected role of PP in regulating the neuroinflammatory pathology of AD in a mouse model.


Assuntos
Doença de Alzheimer , Humanos , Camundongos , Animais , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/psicologia , Doença de Alzheimer/veterinária , PPAR gama , Proteínas do Soro do Leite , Pós , Doenças Neuroinflamatórias/veterinária , Proteínas tau/metabolismo , Camundongos Transgênicos , Transdução de Sinais , Modelos Animais de Doenças
20.
Opt Express ; 31(12): 19126-19132, 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37381336

RESUMO

In this paper, a continuous-wave Nd:YAG InnoSlab laser at 1319 nm with high output power and high beam quality is demonstrated. The maximum output power of 170 W at 1319-nm single wavelength is obtained with an optical-to-optical efficiency of 15.3% from absorbed pump power to laser output and the corresponding slope efficiency of 26.7%. The beam quality factors of M2 are 1.54 and 1.78 in the horizontal and vertical directions, respectively. To the best of our knowledge, this is the first report on Nd:YAG 1319-nm InnoSlab lasers with such high output power and good beam quality.

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