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1.
Opt Express ; 32(6): 9161-9170, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38571155

RESUMO

Reflective cholesteric liquid crystal (CLC) Pancharatnam-Berry phase lens (PBL) devices have attracted significant attention in augmented reality (AR) display due to their wide spectral and angular response bandwidths, high diffraction efficiency, and polarization selectivity. However, currently reported CLC reflective PBLs are either limited by monochrome display or suffers from complicated design for colorful display. Herein, we demonstrate a colorful multi-plane AR display system with dynamically tunable reflective PBL. The reflective PBL is fabricated by polymer-stabilized cholesteric liquid crystal (PSCLC) that provides dynamical and continuous tunability of color and focal length by direct current (DC) voltage. A proof-of-concept colorful multi-plane AR device is demonstrated, where over 90% diffraction efficiency at desired wavelength has been obtained. The proposed simple, compact, and light AR display system capable of color-imaging with multi-depth shows great application potential in the vehicle-mounted head-up display (HUD).

2.
Bioorg Chem ; 147: 107377, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38653150

RESUMO

The first systematic acylated diversification of naturally scarce premyrsinane diterpenes, together with their biosynthetic precursors lathyrane diterpene were carried out. Two new series of premyrsinane derivates (1a-32a) and lathyrane derivates (1-32) were synthesized from the naturally abundant lathyrane diterpene Euphorbia factor L3 through a bioinspired approach. The cholinesterase inhibitory and neuroprotective activities of these diterpenes were investigated to explore potential anti-Alzheimer's disease (AD) bioactive lead compounds. In general, the lathyrane diterpenes showed the better acetylcholinesterase (AChE) inhibitory activity than that of premyrsinanes. The lathyrane derivative 17 bearing a 3-dimethylaminobenzoyl moiety showed the best AChE inhibition effect with the IC50 value of 7.1 µM. Molecular docking demonstrated that 17 could bond with AChE well (-8 kal/mol). On the other hand, premyrsinanes showed a better neuroprotection profile against H2O2-induced injury in SH-SY5Y cells. Among them, the premyrsinane diterpene 16a had significant neuroprotective effect with the cell viability rate of 113.5 % at 12.5 µM (the model group with 51.2 %). The immunofluorescence, western blot and reactive oxygen species (ROS) analysis were conducted to demonstrate the mechanism of 16a. Furthermore, a preliminary SAR analysis of the two categories of diterpenes was performed to provide the insights for anti-AD drug development.

3.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1869(5): 159495, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38609006

RESUMO

Sea cucumber phospholipids, including the plasmalogen (PlsEtn) and plasmanylcholine (PakCho), have been shown to play a regulatory role in lipid metabolism disorders, but their mechanism of action remains unclear. Therefore, high-fat diet (HFD) and palmitic acid were used to establish lipid accumulation models in mice and HepG2 cells, respectively. Results showed that PlsEtn can reduce lipid deposition both in vivo and in vitro. HFD stimulation abnormally activated lipophagy through the phosphorylation of the AMPK/ULK1 pathway. The lipophagy flux monitor revealed abnormalities in the fusion stage of lipophagy. Of note, only PlsEtn stimulated the dynamic remodeling of the autophagosome membrane, which was indicated by the significantly decreased LC3 II/I ratio and p62 level. In all experiments, the effect of PlsEtn was significantly higher than that of PakCho. These findings elucidated the mechanism of PlsEtn in alleviating lipid accumulation, showed that it might be a lipophagy enhancer, and provided new insights into the high-value utilization of sea cucumber as an agricultural resource.

4.
J Agric Food Chem ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630981

RESUMO

The sea cucumber plasmalogen PlsEtn has been shown to be associated with various chronic diseases related to lipid metabolism. However, the mechanism is unclear. Therefore, the present study used the sea cucumber plasmanylcholine PakCho as a structural contrast to PlsEtn and assessed its effect in 8 week high-fat diet (HFD)-fed mice. The lipidomic approach based on high-resolution mass spectrometry combined with molecular biology techniques was used to evaluate the mechanism of PlsEtn. The results showed that both PlsEtn and PakCho significantly inhibited an increase in mouse body weight and liver total triglyceride and total cholesterol levels caused by HFD. In addition, oil red O staining demonstrated that lipid droplets stored in the liver were degraded. Meanwhile, untargeted lipidomic experiments revealed that total lipids (increased by 42.8 mmol/mg prot; p < 0.05), triglycerides (increased by 38.9 mmol/mg prot; p < 0.01), sphingolipids (increased by 1.5 mmol/mg prot; p < 0.0001), and phospholipids (increased by 2.5 mmol/mg prot; p < 0.05) were all significantly elevated under HFD. PlsEtn resolved lipid metabolism disorders by alleviating the abnormal expression of lipid subclasses. In addition, five lipid molecular species, PE (18:1/20:4), PE (18:1/20:3), PE (18:1/18:3), TG (16:0/16:0/17:0), and TG (15:0/16:0/18:1), were identified as the biomarkers of HFD-induced lipid metabolism disorders. Finally, lipophagy-associated protein expression analysis showed that HFD abnormally activated lipophagy via ULK1 phosphorylation and PlsEtn alleviated lipophagy disorder through lysosomal function promotion. In addition, PlsEtn performed better than PakCho. Taken together, the current study results unraveled the mechanism of PlsEtn in alleviating lipid metabolism disorder and offered a new theoretical foundation for the high-value development of sea cucumber.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38648128

RESUMO

In this article, a novel adaptive control method based on neural networks is proposed for a class of multiagent systems (MASs) with nonlinear functions and external disturbances. First, the approximation properties of neural networks are used to approximate the MAS partial differential equation (PDE) model with nonlinear terms containing two variables, time t, and spatial variable x. Second, an adaptive controller is constructed to actuate the parabolic MAS to reach consensus under external disturbances. Based on this, the finite-time theorem and special inequalities are applied to prove the stability of the closed-loop system. Thus, MAS that have nonlinear functions and external disturbances are enabled with finite-time consensus. Finally, the effectiveness of the proposed control method is demonstrated by numerical simulations.

6.
J Proteome Res ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38634357

RESUMO

Gut microbiota-derived microbial compounds may link to the pathogenesis of colorectal cancer (CRC). However, the role of the host-microbiome in the incidence and progression of CRC remains elusive. We performed 16S rRNA sequencing, metabolomics, and proteomic studies on samples from 85 CRC patients who underwent colonoscopy examination and found two distinct changed patterns of microbiome in CRC patients. The relative abundances of Catabacter and Mogibacterium continuously increased from intramucosal carcinoma to advanced stages, whereas Clostridium, Anaerostipes, Vibrio, Flavonifractor, Holdemanella, and Hungatella were significantly altered only in intermediate lesions. Fecal metabolomics analysis exhibited consistent increases in bile acids, indoles, and urobilin as well as a decrease in heme. Serum metabolomics uncovered the highest levels of bilin, glycerides, and nucleosides together with the lowest levels of bile acids and amino acids in the stage of intermediate lesions. Three fecal and one serum dipeptides were elevated in the intermediate lesions. Proteomics analysis of colorectal tissues showed that oxidation and autophagy through the PI3K/Akt-mTOR signaling pathway contribute to the development of CRC. Diagnostic analysis showed multiomics features have good predictive capability, with AUC greater than 0.85. Our overall findings revealed new candidate biomarkers for CRC, with potentially significant diagnostic and prognostic capabilities.

7.
J Agric Food Chem ; 72(12): 6118-6132, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38477232

RESUMO

Cardiovascular diseases are caused by hypercholesterolemia. Astaxanthin (AST) has been reported to exhibit antioxidant and anti-inflammatory properties. However, its bioavailability is poor because of low solubility and instability. In order to improve the bioavailability of AST, we developed an intestinal-responsive composite carrier termed as "liposomes in micropheres" incorporating N-succinyl-chitosan (NSC)-poly(ethylene glycol) (PEG) liposomes that functionalized by neonatal Fc receptors (FcRn) into hydrogels of sodium alginate (SA) and carboxymethyl chitosan (CMCS). In the AST NSC/HSA-PEG liposomes@SA/CMCS microspheres, the AST's encapsulation efficiency (EE) was 96.26% (w/w) and its loading capacity (LC) was 6.47% (w/w). AST NSC/HSA-PEG liposomes had stability in the gastric conditions and achieved long-term release of AST in intestinal conditions. Then, AST NSC/HSA-PEG liposomes@SA/CMCS bind to intestinal epithelial cell targets by the neonatal Fc receptor. In vitro permeation studies show that there was a 4-fold increase of AST NSC/HSA-PEG liposomes@SA/CMCS in AST permeation across the intestinal epithelium. Subsequent in vivo experiments demonstrated that the composite carrier exhibited a remarkable mucoadhesive capacity, allowing for extended intestinal retention of up to 12 h, and it displayed deep penetration through the mucus layer, efficiently entering the intestinal villi epithelial cells, and enhancing the absorption of AST and its bioavailability in vivo. And oral administration of AST NSC/HSA-PEG liposomes@SA/CMCS could effectively prevent hypercholesterolemia caused by a high-fat, high-cholesterol diet (HFHCD). These advancements highlight the potential of NSC/HSA-PEG liposomes@SA/CMCS composite carriers for targeted and oral uptake of hydrophobic bioactives.


Assuntos
Quitosana , Hipercolesterolemia , Recém-Nascido , Humanos , Lipossomos/química , Microesferas , Xantofilas , Quitosana/química , Portadores de Fármacos/química , Administração Oral
8.
Front Immunol ; 15: 1392734, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38515740

RESUMO

[This corrects the article DOI: 10.3389/fimmu.2024.1258740.].

9.
Front Cell Infect Microbiol ; 14: 1283737, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38529471

RESUMO

Gallstones are crystalline deposits in the gallbladder that are traditionally classified as cholesterol, pigment, or mixed stones based on their composition. Microbiota and host metabolism variances among the different types of gallstones remain largely unclear. Here, the bile and gallstone microbial species spectra of 29 subjects with gallstone disease (GSD, 24 cholesterol and 5 pigment) were revealed by type IIB restriction site-associated DNA microbiome sequencing (2bRAD-M). Among them (21 subjects: 18 cholesterol and 3 pigment), plasma samples were subjected to liquid chromatography-mass spectrometry (LC-MS) untargeted metabolomics. The microbiome yielded 896 species comprising 882 bacteria, 13 fungi, and 1 archaeon. Microbial profiling revealed significant enrichment of Cutibacterium acnes and Microbacterium sp005774735 in gallstone and Agrobacterium pusense and Enterovirga sp013044135 in the bile of cholesterol GSD subjects. The metabolome revealed 2296 metabolites, in which malvidin 3-(6''-malonylglucoside), 2-Methylpropyl glucosinolate, and ergothioneine were markedly enriched in cholesterol GSD subjects. Metabolite set enrichment analysis (MSEA) demonstrated enriched bile acids biosynthesis in individuals with cholesterol GSD. Overall, the multi-omics analysis revealed that microbiota and host metabolism interaction perturbations differ depending on the disease type. Perturbed gallstone type-related microbiota may contribute to unbalanced bile acids metabolism in the gallbladder and host, representing a potential early diagnostic marker and therapeutic target for GSD.


Assuntos
Cálculos Biliares , Humanos , Cálculos Biliares/química , Cálculos Biliares/metabolismo , Cálculos Biliares/microbiologia , Ácidos e Sais Biliares/análise , Bile/química , Bile/metabolismo , Colesterol/metabolismo
10.
Arch Insect Biochem Physiol ; 115(3): e22104, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38506277

RESUMO

As a common defense mechanism in Hymenoptera, bee venom has complex components. Systematic and comprehensive analysis of bee venom components can aid in early evaluation, accurate diagnosis, and protection of organ function in humans in cases of bee stings. To determine the differences in bee venom composition and metabolic pathways between Apis cerana and Apis mellifera, proton nuclear magnetic resonance (1 H-NMR) technology was used to detect the metabolites in venom samples. A total of 74 metabolites were identified and structurally analyzed in the venom of A. cerana and A. mellifera. Differences in the composition and abundance of major components of bee venom from A. cerana and A. mellifera were mapped to four main metabolic pathways: valine, leucine and isoleucine biosynthesis; glycine, serine and threonine metabolism; alanine, aspartate and glutamate metabolism; and the tricarboxylic acid cycle. These findings indicated that the synthesis and metabolic activities of proteins or polypeptides in bee venom glands were different between A. cerana and A. mellifera. Pyruvate was highly activated in 3 selected metabolic pathways in A. mellifera, being much more dominant in A. mellifera venom than in A. cerana venom. These findings indicated that pyruvate in bee venom glands is involved in various life activities, such as biosynthesis and energy metabolism, by acting as a precursor substance or intermediate product.


Assuntos
Venenos de Abelha , Himenópteros , Mordeduras e Picadas de Insetos , Humanos , Abelhas , Animais , Ácido Pirúvico , Espectroscopia de Ressonância Magnética
11.
Psychol Sci ; 35(4): 328-344, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38483515

RESUMO

With the rapid spread of information via social media, individuals are prone to misinformation exposure that they may utilize when forming beliefs. Over five experiments (total N = 815 adults, recruited through Amazon Mechanical Turk in the United States), we investigated whether people could ignore quantitative information when they judged for themselves that it was misreported. Participants recruited online viewed sets of values sampled from Gaussian distributions to estimate the underlying means. They attempted to ignore invalid information, which were outlier values inserted into the value sequences. Results indicated participants were able to detect outliers. Nevertheless, participants' estimates were still biased in the direction of the outlier, even when they were most certain that they detected invalid information. The addition of visual warning cues and different task scenarios did not fully eliminate systematic over- and underestimation. These findings suggest that individuals may incorporate invalid information they meant to ignore when forming beliefs.


Assuntos
Comunicação , Sinais (Psicologia) , Adulto , Humanos , Estados Unidos
12.
Obes Surg ; 34(5): 1608-1617, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38530552

RESUMO

INTRODUCTION: Bariatric surgery (BS) patients are advised to consume protein supplements to prevent fat-free mass (FFM) loss. However, limited research has explored the efficacy of diverse protein presentations on FFM preservation. This study assesses if short peptide-based (SPB) supplements surpass complex protein-based (CPB) supplements in reducing early FFM loss post-surgery. METHODS: In this retrospective cohort study, 138 patients who underwent BS other than Roux-en-Y-gastric bypass (RYGB) between January 2021 and March 2021 at the Department of Bariatric Surgery of the Third People's Hospital of Chengdu were included for analysis. Patients were divided into two groups based on their consumption of protein supplements after surgery: SPB group and CPB group. Multiple linear regressions separated by sex were employed to examine the associations between SPB supplements and FFM loss and percentage of FFM (%FFM) loss, respectively. RESULTS: Among participants, 69.6% were female, with a mean age of 33.3 years. In multiple linear regression analyses, SPB supplements were significantly and positively associated with a lower FFM loss in both female (ꞵ = - 1.14, P = 0.047) and male (ꞵ = - 2.36, P = 0.024), and were positively associated with a lower %FFM loss in both female (ꞵ = - 1.83) and male (ꞵ = - 2.26) but only significant in male (P = 0.049). CONCLUSION: SPB supplements may be more effective in preventing early FFM loss after BS, compared to CPB supplements, particularly among male patients. Therefore, SPB supplements may be recommended to patients undergoing BS. Further research is needed to validate these findings.


Assuntos
Cirurgia Bariátrica , Derivação Gástrica , Obesidade Mórbida , Humanos , Masculino , Feminino , Adulto , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Composição Corporal , Derivação Gástrica/efeitos adversos , Peptídeos
13.
Proc Natl Acad Sci U S A ; 121(14): e2317492121, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38547056

RESUMO

Energy metabolism is highly interdependent with adaptive cell migration in vivo. Mechanical confinement is a critical physical cue that induces switchable migration modes of the mesenchymal-to-amoeboid transition (MAT). However, the energy states in distinct migration modes, especially amoeboid-like stable bleb (A2) movement, remain unclear. In this report, we developed multivalent DNA framework-based nanomachines to explore strategical mitochondrial trafficking and differential ATP levels during cell migration in mechanically heterogeneous microenvironments. Through single-particle tracking and metabolomic analysis, we revealed that fast A2-moving cells driven by biomimetic confinement recruited back-end positioning of mitochondria for powering highly polarized cytoskeletal networks, preferentially adopting an energy-saving mode compared with a mesenchymal mode of cell migration. We present a versatile DNA nanotool for cellular energy exploration and highlight that adaptive energy strategies coordinately support switchable migration modes for facilitating efficient metastatic escape, offering a unique perspective for therapeutic interventions in cancer metastasis.


Assuntos
Amoeba , Linhagem Celular Tumoral , Movimento Celular , Fenômenos Físicos
14.
Food Funct ; 15(8): 4037-4050, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38533894

RESUMO

Frequent consumption of fried foods has been strongly associated with a higher risk of anxiety and depression, particularly among young individuals. The existing evidence has indicated that acrylamide produced from starchy foods at high temperatures can induce anxious behavior. However, there is limited research on the nerve damage caused by thermo-induced oxidized oil (TIOO). In this study, we conducted behavioral tests on mice and found that prolonged consumption of TIOO led to significant anxiety behavior and a tendency toward depression. TIOO primarily induced these two emotional disorders by affecting the differentiation of microglia, the level of inflammatory factors, the activation of astrocytes, and glutamate circulation in brain tissue. By promoting the over-differentiation of microglia into M1 microglia, TIOO disrupted their differentiation balance, resulting in an up-regulation of inflammatory factors (IL-1ß, IL-6, TNF-α, NOS2) in M1 microglia and a down-regulation of neuroprotective factors IL-4/IL-10 in M2 microglia, leading to nerve damage. Moreover, TIOO activated astrocytes, accelerating their proliferation and causing GFAP precipitation, which damaged astrocytes. Meanwhile, TIOO stimulates the secretion of the BDNF and reduces the level of the glutamate receptor GLT-1 in astrocytes, leading to a disorder in the glutamate-glutamine cycle, further exacerbating nerve damage. In conclusion, this study suggests that long-term intake of thermo-induced oxidized oil can trigger symptoms of anxiety and depression.


Assuntos
Ansiedade , Astrócitos , Depressão , Microglia , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Microglia/efeitos dos fármacos , Camundongos , Masculino , Oxirredução , Camundongos Endogâmicos C57BL , Temperatura Alta , Comportamento Animal/efeitos dos fármacos
15.
Front Endocrinol (Lausanne) ; 15: 1334342, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38469147

RESUMO

Early-onset obesity is a rising health concern influenced by heredity. However, many monogenic obesity variants (MOVs) remain to be discovered due to differences in ethnicity and culture. Additionally, patients with known MOVs have shown limited weight loss after bariatric surgery, suggesting it can be used as a screening tool for new candidates. In this study, we performed whole-exome sequencing (WES) combined with postoperative data to detect candidate MOVs in a cohort of 62 early-onset obesity and 9 late-onset obesity patients. Our findings demonstrated that patients with early-onset obesity preferred a higher BMI and waist circumference (WC). We confirmed the efficacy of the method by identifying a mutation in known monogenic obesity gene, PCSK1, which resulted in less weight loss after surgery. 5 genes were selected for further verification, and a frameshift variant in CAMKK2 gene: NM_001270486.1, c.1614dup, (p. Gly539Argfs*3) was identified as a novel candidate MOV. This mutation influenced the improvement of metabolism after bariatric surgery. In conclusion, our data confirm the efficacy of WES combined with postoperative data in detecting novel candidate MOVs and c.1614dup (CAMKK2) might be a promising MOV, which needs further confirmation. This study enriches the human monogenic obesity mutation database and provides a scientific basis for clinically accurate diagnosis and treatment.


Assuntos
Mutação da Fase de Leitura , Obesidade , Humanos , Sequenciamento do Exoma , Obesidade/genética , Obesidade/cirurgia , Mutação , Redução de Peso , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/genética
16.
Quant Imaging Med Surg ; 14(3): 2455-2465, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38545046

RESUMO

Background: Despite being a major focus of medical research for decades, rectal cancer remains a major threat to human health. This study aimed to compare and analyze the diagnostic value of transrectal ultrasonography (TRUS) for rectal adenoma and early-stage rectal cancer before and after gastrointestinal agent instillation. Methods: In this prospective study, patients diagnosed with rectal adenomas and early-stage rectal cancer by ultrasound were randomly selected for inclusion. All patients underwent ultrasound examination at the Outpatient Department of the First Affiliated Hospital of China Medical University and underwent surgical treatment at the First Affiliated Hospital of China Medical University. Patients with a lesion located 13 cm or more from the edge of the anus, or history of surgery, and a history of radiation and chemotherapy were excluded. A gastrointestinal agent was directly instilled into the rectal cavity during conventional TRUS to compare and analyze the display of rectal lesions before and after such instillation and to evaluate the infiltration depth of rectal lesions. These findings were compared to the pathological findings to determine the diagnostic efficacy. Results: Both the conventional TRUS and TRUS with gastrointestinal agent instillation were able to show the rectal wall structure and rectal lesions; the detection rate of rectal lesions of the former was 75.0%, and that of the latter was 97.1% (P<0.001). Of the 27 rectal adenomas, conventional TRUS detected 10, and TRUS with gastrointestinal agent instillation detected 25 lesions. The accuracy [90.54%; 95% confidence interval (CI): 81.48-96.11%; P=1.05E-08], specificity (87.88%; 95% CI: 71.80-96.60%; P=1.09E-05), and sensitivity (92.68%; 95% CI: 80.08-98.47%; P=1.05E-08) of TRUS in diagnosing early-stage rectal cancer were consistent with the pathological findings (P<0.001). The accuracy (95.95%, 95% CI: 88.61-99.16%; P=3.82E-11), specificity (93.94%, 95% CI: 79.77-99.26%; P=1.31E-07), and sensitivity (97.56%, 95% CI: 87.15-99.94%; P=3.82E-11) of TRUS after gastrointestinal agent infusion in diagnosing early-stage rectal cancer were consistent with the pathological findings (P<0.001). The specificity (87.88%; 95% CI: 71.80-96.60%; P=1.09E-05) of TRUS in diagnosing rectal adenomas was consistent with the pathological finding (P<0.001), but the accuracy (65%; 95% CI: 51.60-76.87%; P=0.25) and sensitivity (37.04%, 95% CI: 19.40-57.63%; P=0.25) were not (P>0.05). Meanwhile, the accuracy (93.33%; 95% CI: 83.80-98.15%; P=5.65E-06), specificity (93.94; 95% CI: 79.77-99.26%; P=1.31E-07), and sensitivity (92.59%; 95% CI: 75.71-99.09%; P=5.65E-06) of TRUS after gastrointestinal agent infusion in diagnosing rectal adenomas were consistent with the pathological findings (P<0.001). Conclusions: TRUS with gastrointestinal agent instillation had significantly improved accuracy in diagnosing early-stage rectal cancer and detecting intrarectal adenomatoid lesions.

17.
Cell Mol Biol Lett ; 29(1): 32, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443798

RESUMO

RNA-binding proteins (RBPs) are kinds of proteins with either singular or multiple RNA-binding domains (RBDs), and they can assembly into ribonucleic acid-protein complexes, which mediate transportation, editing, splicing, stabilization, translational efficiency, or epigenetic modifications of their binding RNA partners, and thereby modulate various physiological and pathological processes. CUG-BP, Elav-like family 1 (CELF1) is a member of the CELF family of RBPs with high affinity to the GU-rich elements in mRNA, and thus exerting control over critical processes including mRNA splicing, translation, and decay. Mounting studies support that CELF1 is correlated with occurrence, genesis and development and represents a potential therapeutical target for these malignant diseases. Herein, we present the structure and function of CELF1, outline its role and regulatory mechanisms in varieties of homeostasis and diseases, summarize the identified CELF1 regulators and their structure-activity relationships, and prospect the current challenges and their solutions during studies on CELF1 functions and corresponding drug discovery, which will facilitate the establishment of a targeted regulatory network for CELF1 in diseases and advance CELF1 as a potential drug target for disease therapy.


Assuntos
Descoberta de Drogas , Epigênese Genética , Homeostase , RNA , RNA Mensageiro
18.
Plant Physiol ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38478469

RESUMO

The Xishuangbanna (XIS) cucumber (Cucumis sativus var. xishuangbannanesis) is a semiwild variety that has many distinct agronomic traits. Here, long -reads generated by Nanopore sequencing technology helped assembling a high-quality genome (contig N50 = 8.7 Mb) of landrace XIS49. A total of 10,036 structural/sequence variations (SVs) were identified when comparing with Chinese Long (CL), and known SVs controlling spines, tubercles, and carpel number were confirmed in XIS49 genome. Two QTLs of hypocotyl elongation under low light, SH3.1 and SH6.1 were fine-mapped using introgression lines (donor parent, XIS49; recurrent parent, CL). SH3.1 encodes a red-light receptor Phytochrome B (PhyB, CsaV3_3G015190). An ∼4 kb large deletion (DEL) and highly divergent regions (HDRs) were identified in the promoter of the PhyB gene in XIS49. Loss of function of this PhyB caused a super-long hypocotyl phenotype. SH6.1 encodes a CCCH-type zinc finger protein FRIGIDA-ESSENTIAL LIKE (FEL, CsaV3_6G050300). FEL negatively regulated hypocotyl elongation but it was transcriptionally suppressed by a long terminal repeats (LTRs) retrotransposon insertion in CL cucumber. Mechanistically, FEL physically binds to the promoter of CONSTITUTIVE PHOTOMORPHOGENIC 1a (COP1a), regulating the expression of COP1a and the downstream hypocotyl elongation. These above results demonstrate the genetic mechanism of cucumber hypocotyl elongation under low light.

19.
Adv Sci (Weinh) ; : e2401254, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38483920

RESUMO

Pancreatic fibrosis (PF) is primarily characterized by aberrant production and degradation modes of extracellular matrix (ECM) components, resulting from the activation of pancreatic stellate cells (PSCs) and the pathological cross-linking of ECM mediated by lysyl oxidase (LOX) family members. The excessively deposited ECM increases matrix stiffness, and the over-accumulated reactive oxygen species (ROS) induces oxidative stress, which further stimulates the continuous activation of PSCs and advancing PF; challenging the strategy toward normalizing ECM homeostasis for the regression of PF. Herein, ROS-responsive and Vitamin A (VA) decorated micelles (named LR-SSVA) to reverse the imbalanced ECM homeostasis for ameliorating PF are designed and synthesized. Specifically, LR-SSVA selectively targets PSCs via VA, thereby effectively delivering siLOXL1 and resveratrol (RES) into the pancreas. The ROS-responsive released RES inhibits the overproduction of ECM by eliminating ROS and inactivating PSCs, meanwhile, the decreased expression of LOXL1 ameliorates the cross-linked collagen for easier degradation by collagenase which jointly normalizes ECM homeostasis and alleviates PF. This research shows that LR-SSVA is a safe and efficient ROS-response and PSC-targeted drug-delivery system for ECM normalization, which will propose an innovative and ideal platform for the reversal of PF.

20.
Huan Jing Ke Xue ; 45(3): 1577-1585, 2024 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-38471871

RESUMO

The adsorption characteristics of ammonia nitrogen for constructed wetland were studied with ceramsite, quartz sand, and gravel. The material was characterized using scanning electron microscopy and a BET-specific surface area analyzer. It was found that the surface of ceramide was coarser than that of quartz sand and gravel, and the internal pores were more developed. The specific surface area of ceramide (18.97 m2·g-1) was higher than that of quartz sand and gravel. In the pure ammonia nitrogen solution and Grade I B standard for the wastewater treatment plant effluent ammonia nitrogen solution of the effluent from the simulated sewage plant, the adsorption capacity of the three substrates was as follows:ceramsite > gravel > quartz sand. The saturated adsorption capacity (63.55 m2·g-1) of ceramides was the highest in the mixed solution. The adsorption process of ammonia nitrogen by ceramides accorded with the pseudo-second-order kinetic model (R2 of 0.99 in the pure ammonia nitrogen solution and 0.98 in the mixed solution). The Freundlich and Langmuir models were used to fit the isothermal adsorption results in a pure ammonia nitrogen solution. It was found that the Freundlich model described the adsorption characteristics of the ceramics more accurately than the Langmuir model (R2=0.93), indicating that the adsorption of ammonia nitrogen by the ceramics was multilayer adsorption. In conclusion, the adsorption capacity of ceramide was strong, and the adsorption capacity of ceramide in the mixed solution was 31% higher than that in the pure ammonia nitrogen solution, which was suitable to be used as the matrix filler of constructed wetland.

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