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1.
Adv Mater ; : e2400493, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38733358

RESUMO

Full-Stokes polarization detection, with high integration and portability, offers an efficient path toward next-gen multi-information optoelectronic systems. Nevertheless, current techniques relying on optical filters create rigid and bulky configurations, limiting practicality. Here, we first report a flexible, filter-less full-Stokes polarimeter featuring a uniaxial-oriented chiral perovskite film. We find that, the strategic manipulation of the surfactant-mediated Marangoni effect during blade coating, is crucial for guiding an equilibrious mass transport to achieve oriented crystallization. Through this approach, the obtained uniaxial-oriented chiral perovskite films inherently possess anisotropy and chirality, and thereby with desired sensitivity to both Linearly Polarized Light (LPL) and Circularly Polarized Light (CPL) vectors. The uniaxial-oriented crystalline structure also improves photodetection, achieving a specific detectivity of 5.23 × 1013 Jones, surpassing non-oriented devices by 10x. The as-fabricated flexible polarimeters enable accurate capture of full-Stokes polarization without optical filters, exhibiting slight detection errors for the Stokes parameters: ΔS1 = 9.2%, ΔS2 = 8.6%, and ΔS3 = 6.5%, approaching the detection accuracy of optics-filter polarimeters. Our proof of concept also demonstrates applications in matrix polarization imaging. This article is protected by copyright. All rights reserved.

2.
Int J Mol Sci ; 25(9)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38731915

RESUMO

The mammalian pituitary gland drives highly conserved physiological processes such as somatic cell growth, pubertal transformation, fertility, and metabolism by secreting a variety of hormones. Recently, single-cell transcriptomics techniques have been used in pituitary gland research. However, more studies have focused on adult pituitary gland tissues from different species or different sexes, and no research has yet resolved cellular differences in pituitary gland tissue before and after sexual maturation. Here, we identified a total of 15 cell clusters and constructed single-cell transcriptional profiles of rats before and after sexual maturation. Furthermore, focusing on the gonadotrope cluster, 106 genes were found to be differentially expressed before and after sexual maturation. It was verified that Spp1, which is specifically expressed in gonadotrope cells, could serve as a novel marker for this cell cluster and has a promotional effect on the synthesis and secretion of follicle-stimulating hormone. The results provide a new resource for further resolving the regulatory mechanism of pituitary gland development and pituitary hormone synthesis and secretion.


Assuntos
Gonadotrofos , Hipófise , Maturidade Sexual , Análise de Célula Única , Animais , Ratos , Maturidade Sexual/genética , Hipófise/metabolismo , Gonadotrofos/metabolismo , Análise de Célula Única/métodos , Masculino , Feminino , Biomarcadores/metabolismo , Transcriptoma , Perfilação da Expressão Gênica , Hormônio Foliculoestimulante/metabolismo
3.
Curr Med Sci ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38748367

RESUMO

Maxillary protrusion combined with mandibular retraction is a highly prevalent but extremely complex maxillofacial deformity that can have a serious negative impact on patients' facial aesthetics and mental health. The traditional orthodontic treatment strategy often involves extracting 4 first premolars and conventional fixed techniques, combined with mini-implant screws, to retract the anterior teeth and improve facial protrusion. In recent years, an invisible orthodontic technique, without brackets, has become increasingly popular. However, while an invisible aligner has been used in some cases with reasonable results, there remain significant challenges in achieving a perfect outcome. This case report presents an adolescent patient with bimaxillary protrusion and mandibular retrognathia. Based on the characteristics of the invisible aligners and the growth characteristics of the adolescent's teeth and jawbone, we designed precise three-dimensional tooth movement and corresponding resistance/over-correction for each tooth, while utilizing the patient's jawbone growth potential to promote rapid development of the mandible, accurately and efficiently correcting bimaxillary protrusion and skeletal mandibular retrognathia. The patient's facial aesthetics, especially the lateral morphology, have been greatly improved, and various aesthetic indicators have also shown significant changes, and to the patient's great benefit, invasive mini-implant screws were not used during the treatment. This case highlights the advantages of using invisible aligners in adolescent maxillary protrusion combined with mandibular retraction patients. Furthermore, comprehensive and accurate design combined with good application of growth potential can also enable invisible orthodontic technology to achieve perfect treatment effects in tooth extractions, providing clinical guidance for orthodontists.

4.
Neural Netw ; 176: 106354, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38723308

RESUMO

Neural operators, as a powerful approximation to the non-linear operators between infinite-dimensional function spaces, have proved to be promising in accelerating the solution of partial differential equations (PDE). However, it requires a large amount of simulated data, which can be costly to collect. This can be avoided by learning physics from the physics-constrained loss, which we refer to it as mean squared residual (MSR) loss constructed by the discretized PDE. We investigate the physical information in the MSR loss, which we called long-range entanglements, and identify the challenge that the neural network requires the capacity to model the long-range entanglements in the spatial domain of the PDE, whose patterns vary in different PDEs. To tackle the challenge, we propose LordNet, a tunable and efficient neural network for modeling various entanglements. Inspired by the traditional solvers, LordNet models the long-range entanglements with a series of matrix multiplications, which can be seen as the low-rank approximation to the general fully-connected layers and extracts the dominant pattern with reduced computational cost. The experiments on solving Poisson's equation and (2D and 3D) Navier-Stokes equation demonstrate that the long-range entanglements from the MSR loss can be well modeled by the LordNet, yielding better accuracy and generalization ability than other neural networks. The results show that the Lordnet can be 40× faster than traditional PDE solvers. In addition, LordNet outperforms other modern neural network architectures in accuracy and efficiency with the smallest parameter size.

5.
Biomed Environ Sci ; 37(4): 377-386, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38727160

RESUMO

Objective: This study aimed to investigate the lipid-lowering activity of LFBEP-C1 in high glucose-fed Caenorhabditis elegans (C. elegans). Methods: In this study, the fermented barley protein LFBEP-C1 was prepared and tested for its potential anti-obesity effects on C. elegans. The worms were fed Escherichia coli OP50 ( E. coli OP50), glucose, and different concentrations of LFBEP-C1. Body size, lifespan, movement, triglyceride content, and gene expression were analyzed. The results were analyzed using ANOVA and Tukey's multiple comparison test. Results: Compared with the model group, the head-swing frequency of C. elegans in the group of LFBEP-C1 at 20 µg/mL increased by 33.88%, and the body-bending frequency increased by 27.09%. This indicated that LFBEP-C1 improved the locomotive ability of C. elegans. The average lifespan of C. elegans reached 13.55 days, and the body length and width of the C. elegans decreased after LFBEP-C1 intake. Additionally, LFBEP-C1 reduced the content of lipid accumulation and triglyceride levels. The expression levels of sbp-1, daf-2, and mdt-15 significantly decreased, while those of daf-16, tph-1, mod-1, and ser-4 significantly increased after LFBEP-C1 intake. Changes in these genes explain the signaling pathways that regulate lipid metabolism. Conclusion: LFBEP-C1 significantly reduced lipid deposition in C. elegans fed a high-glucose diet and alleviated the adverse effects of a high-glucose diet on the development, lifespan, and exercise behavior of C. elegans. In addition, LFBEP-C1 regulated lipid metabolism mainly by mediating the expression of genes in the sterol regulatory element-binding protein, insulin, and 5-hydroxytryptamine signaling pathways.


Assuntos
Caenorhabditis elegans , Hordeum , Metabolismo dos Lipídeos , Animais , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/metabolismo , Hordeum/química , Metabolismo dos Lipídeos/efeitos dos fármacos , Fermentação , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Lactobacillus plantarum , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética
6.
Biomed Mater ; 19(4)2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38697132

RESUMO

During the process of malignant tumor treatment, photodynamic therapy (PDT) exerts poor efficacy due to the hypoxic environment of the tumor cells, and long-time chemotherapy reduces the sensitivity of tumor cells to chemotherapy drugs due to the presence of drug-resistant proteins on the cell membranes for drug outward transportation. Therefore, we reported a nano platform based on mesoporous silica coated with polydopamine (MSN@PDA) loading PDT enhancer MnO2, photosensitizer indocyanine green (ICG) and chemotherapeutic drug doxorubicin (DOX) (designated as DMPIM) to achieve a sequential release of different drugs to enhance treatment of malignant tumors. MSN was first synthesized by a template method, then DOX was loaded into the mesoporous channels of MSN, and locked by the PDA coating. Next, ICG was modified by π-π stacking on PDA, and finally, MnO2layer was accumulated on the surface of DOX@MSN@PDA- ICG@MnO2, achieving orthogonal loading and sequential release of different drugs. DMPIM first generated oxygen (O2) through the reaction between MnO2and H2O2after entering tumor cells, alleviating the hypoxic environment of tumors and enhancing the PDT effect of sequentially released ICG. Afterwards, ICG reacted with O2in tumor tissue to produce reactive oxygen species, promoting lysosomal escape of drugs and inactivation of p-glycoprotein (p-gp) on tumor cell membranes. DOX loaded in the MSN channels exhibited a delay of approximately 8 h after ICG release to exert the enhanced chemotherapy effect. The drug delivery system achieved effective sequential release and multimodal combination therapy, which achieved ideal therapeutic effects on malignant tumors. This work offers a route to a sequential drug release for advancing the treatment of malignant tumors.


Assuntos
Doxorrubicina , Liberação Controlada de Fármacos , Verde de Indocianina , Indóis , Compostos de Manganês , Óxidos , Fotoquimioterapia , Fármacos Fotossensibilizantes , Polímeros , Fotoquimioterapia/métodos , Doxorrubicina/química , Doxorrubicina/farmacologia , Doxorrubicina/administração & dosagem , Verde de Indocianina/química , Indóis/química , Animais , Compostos de Manganês/química , Humanos , Polímeros/química , Linhagem Celular Tumoral , Óxidos/química , Fármacos Fotossensibilizantes/química , Dióxido de Silício/química , Camundongos , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem , Neoplasias/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Portadores de Fármacos/química , Porosidade
7.
Chem Commun (Camb) ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38716634

RESUMO

Rh-catalyzed three-component C(sp3)/C(sp2)-H activation has been achieved through a two-directing group strategy. This protocol provides a convenient and efficient pathway for the construction of diverse 8-alkyl quinoline derivatives in one-pot. Furthermore, mechanistic studies revealed that the first C-H amidation was significantly faster than the sequential C-H alkylation.

8.
Discov Oncol ; 15(1): 143, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38704809

RESUMO

PURPOSE: Pancreatic cancer (PC) is one of the most lethal malignant gastrointestinal tumors (GI) characterized by a poor prognosis. Ferroptosis is an emerging programmed cell death that plays an essential role in the progression of various cancers. Ferroptosis is driven by iron-dependent phospholipid peroxidation and is regulated by mitochondrial activity, lipid peroxidation, and reactive oxygen species (ROS). The function and mechanism of ferroptosis in PC need more research. METHODS: The levels of circRNAs, miRNAs, and mRNAs were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was used for protein detection. CCK8 assays were used to detect cell proliferation. Cell death, lipid peroxidation, ROS, and Fe2+ were detected by indicted kits. Dual-luciferase reporter and RNA pull-down assays were conducted to confirm the interaction between circRNAs, miRNAs, and mRNAs. RESULTS: In this research, we found that circular RNA hsa_circ_0000003(circ_WASF2) was upregulated in pancreatic cancer cells. The silence of circ_WASF2 inhibited cancer proliferation and increased cell death by increasing ferroptosis accompanied by up-regulation of lipid peroxidation, ROS, and Fe2+. Further studies showed that circ_WASF2 could attenuate ferroptosis by targeting miR-634 and the downstream glutathione peroxidase 4 (GPX4). GPX4 has been well-reported as a central factor in ferroptosis. Our research revealed a new pathway for regulating ferroptosis in PC. CONCLUSION: In summary, we have determined that circ_WASF2/miR-634/GPX4 contributed to ferroptosis-induced cell death, and provided a possible therapeutic target in PC.

9.
BMC Biol ; 22(1): 104, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702712

RESUMO

BACKGROUND: Gonadotropin precisely controls mammalian reproductive activities. Systematic analysis of the mechanisms by which epigenetic modifications regulate the synthesis and secretion of gonadotropin can be useful for more precise regulation of the animal reproductive process. Previous studies have identified many differential m6A modifications in the GnRH-treated adenohypophysis. However, the molecular mechanism by which m6A modification regulates gonadotropin synthesis and secretion remains unclear. RESULTS: Herein, it was found that GnRH can promote gonadotropin synthesis and secretion by promoting the expression of FTO. Highly expressed FTO binds to Foxp2 mRNA in the nucleus, exerting a demethylation function and reducing m6A modification. After Foxp2 mRNA exits the nucleus, the lack of m6A modification prevents YTHDF3 from binding to it, resulting in increased stability and upregulation of Foxp2 mRNA expression, which activates the cAMP/PKA signaling pathway to promote gonadotropin synthesis and secretion. CONCLUSIONS: Overall, the study reveals the molecular mechanism of GnRH regulating the gonadotropin synthesis and secretion through FTO-mediated m6A modification. The results of this study allow systematic interpretation of the regulatory mechanism of gonadotropin synthesis and secretion in the pituitary at the epigenetic level and provide a theoretical basis for the application of reproductive hormones in the regulation of animal artificial reproduction.


Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato , Hormônio Liberador de Gonadotropina , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Hormônio Liberador de Gonadotropina/metabolismo , Hormônio Liberador de Gonadotropina/genética , Animais , Gonadotropinas/metabolismo , Camundongos , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Metilação de RNA
10.
J Oleo Sci ; 73(5): 761-772, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38692898

RESUMO

Volatile secondary metabolites of plants interact with environments heavily. In this work, characteristic components of Michelia yunnanensis essential oils (EOs) were isolated, purified and identified by column chromatography, GC-MS and NMR. Leaves of M. yunnanensis were collected monthly and extracted for EOs to investigate chemical and insecticidal activity variations as well as potential influencing environments. Different organs were employed to reveal distribution strategies of characteristic components. Results of insecticidal activities showed that all EOs samples exerted stronger contact activity to Lasioderma serricorne, but repellent effect was more efficient on Tribolium castaneum. One oxygenated sesquiterpene was isolated from EOs, basically it could be confirmed as (+)-cyclocolorenone (1). It exerted contact toxicity to L. serricorne (LD 50 = 28.8 µg/adult). Chemical analysis showed that M. yunnanensis leaves in reproductive period would produce and accumulate more 1 than in vegetative period. Moreover, reproductive organs (flowers and fruits) contained more 1 than vegetative organs (leaves and twigs). Partial correlation analysis indicated that temperature-related elements positively correlated with the relative content of 1.


Assuntos
Inseticidas , Óleos Voláteis , Folhas de Planta , Tribolium , Animais , Inseticidas/isolamento & purificação , Inseticidas/análise , Folhas de Planta/química , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Tribolium/efeitos dos fármacos , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/análise , Repelentes de Insetos/análise , Repelentes de Insetos/isolamento & purificação , Repelentes de Insetos/farmacologia , Temperatura
11.
Mol Ecol Resour ; : e13966, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38695851

RESUMO

Parasitic plants have a heterotrophic lifestyle, in which they withdraw all or part of their nutrients from their host through the haustorium. Despite the release of many draft genomes of parasitic plants, the genome evolution related to the parasitism feature of facultative parasites remains largely unknown. In this study, we present a high-quality chromosomal-level genome assembly for the facultative parasite Pedicularis kansuensis (Orobanchaceae), which invades both legume and grass host species in degraded grasslands on the Qinghai-Tibet Plateau. This species has the largest genome size compared with other parasitic species, and expansions of long terminal repeat retrotransposons accounting for 62.37% of the assembly greatly contributed to the genome size expansion of this species. A total of 42,782 genes were annotated, and the patterns of gene loss in P. kansuensis differed from other parasitic species. We also found many mobile mRNAs between P. kansuensis and one of its host species, but these mobile mRNAs could not compensate for the functional losses of missing genes in P. kansuensis. In addition, we identified nine horizontal gene transfer (HGT) events from rosids and monocots, as well as one single-gene duplication events from HGT genes, which differ distinctly from that of other parasitic species. Furthermore, we found evidence for HGT through transferring genomic fragments from phylogenetically remote host species. Taken together, these findings provide genomic insights into the evolution of facultative parasites and broaden our understanding of the diversified genome evolution in parasitic plants and the molecular mechanisms of plant parasitism.

12.
PLoS One ; 19(4): e0296862, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38578800

RESUMO

OBJECTIVE: To investigate the level of screen time and gross motor movement level and the correlation between them in left-behind children aged 3 to 6 years old in China. METHODS: A randomized whole-group sampling method was used to study 817 left-behind children aged 3-6 years in 15 kindergartens in Xiangcheng city, Henan province. The third version of the Test of Gross Motor Development (TGMD-3) was used to test the children's gross motor movement level, and the screen time questionnaire was used to test the children's screen time level. The relationship between the two and the indicators was explored using Pearson's two-sided correlation and multilevel regression. RESULTS: The average daily screen time of left-behind children aged 3-6 years old increased with age, and the reporting rate of >2 h/d ranged from 22.43% to 33.73%; gross motor movement of left-behind children aged 3-6 years old increased with age, with significant differences between age (p<0.05). There was a low to moderate negative correlation (r = -0.133 to -0.354, p<0.05) between screen time and gross motor movement in children aged 3-6 years, and multiple regression analysis showed that screen time was predictive of gross motor movement in children (p<0.05), with an explanation rate of 21.4%. CONCLUSION: There is a correlation between screen time and gross motor movement development in children aged 3-6 years old left behind, and the gross motor movement ability of children aged 3-6 years old can be developed by reducing screen time and increasing physical activity.


Assuntos
Destreza Motora , Tempo de Tela , Criança , Humanos , Pré-Escolar , Estudos Transversais , Exercício Físico , China
13.
Chem Sci ; 15(16): 5869-5896, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38665521

RESUMO

With the continuous development of laser technology and the increasing demand for lasers of different frequencies in the infrared (IR) spectrum, research on infrared nonlinear optical (NLO) crystals has garnered growing attention. Currently, the three main commercially available types of borate materials each have their drawbacks, which limit their applications in various areas. Rare-earth (RE)-based chalcogenide compounds, characterized by the unique f-electron configuration, strong positive charges, and high coordination numbers of RE cations, often exhibit distinctive optical responses. In the field of IR-NLO crystals, they have a research history spanning several decades, with increasing interest. However, there is currently no comprehensive review summarizing and analyzing these promising compounds. In this review, we categorize 85 representative examples out of more than 400 non-centrosymmetric (NCS) compounds into four classes based on the connection of different asymmetric building motifs: (1) RE-based chalcogenides containing tetrahedral motifs; (2) RE-based chalcogenides containing lone-pair-electron motifs; (3) RE-based chalcogenides containing [BS3] and [P2Q6] motifs; and (4) RE-based chalcohalides and oxychalcogenides. We provide detailed discussions on their synthesis methods, structures, optical properties, and structure-performance relationships. Finally, we present several favorable suggestions to further explore RE-based chalcogenide compounds. These suggestions aim to approach these compounds from a new perspective in the field of structural chemistry and potentially uncover hidden treasures within the extensive accumulation of previous research.

14.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 53(2): 231-243, 2024 Apr 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38650448

RESUMO

MiRNAs are a class of small non-coding RNAs, which regulate gene expression post-transcriptionally by partial complementary base pairing. Aberrant miRNA expressions have been reported in tumor tissues and peripheral blood of cancer patients. In recent years, artificial intelligence algorithms such as machine learning and deep learning have been widely used in bioinformatic research. Compared to traditional bioinformatic tools, miRNA target prediction tools based on artificial intelligence algorithms have higher accuracy, and can successfully predict subcellular localization and redistribution of miRNAs to deepen our understanding. Additionally, the construction of clinical models based on artificial intelligence algorithms could significantly improve the mining efficiency of miRNA used as biomarkers. In this article, we summarize recent development of bioinformatic miRNA tools based on artificial intelligence algorithms, focusing on the potential of machine learning and deep learning in cancer-related miRNA research.


Assuntos
Algoritmos , Inteligência Artificial , Biologia Computacional , MicroRNAs , Neoplasias , MicroRNAs/genética , Humanos , Neoplasias/genética , Biologia Computacional/métodos , Aprendizado de Máquina , Aprendizado Profundo
15.
World J Clin Cases ; 12(11): 1990-1995, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38660553

RESUMO

BACKGROUND: When an anorectal foreign body is found, its composition and shape should be evaluated, and a timely and effective treatment plan should be developed based on the patient's symptoms to avoid serious complications such as intestinal perforation caused by displacement of the foreign body. CASE SUMMARY: A 54-year-old male was admitted to our outpatient clinic on June 3, 2023, due to a rectal foreign body that had been embedded for more than 24 h. The patient reported using a glass electrode tube to assist in the recovery of prolapsed hemorrhoids, however, the electrode tube was inadvertently inserted into the anus and could not be removed by the patient. During hospitalization, the patient underwent surgery, and the foreign body was dragged into the rectum with the aid of colonoscopy. The anus was dilated with a comb-type pulling hook and an anal fistula pulling hook to widen the anus and remove the foreign body, and the local anal symptoms were then relieved with topical drugs. The patient was allowed to eat and drink, and an entire abdominal Computed tomography (CT) and colonoscopy were reviewed 3 d after surgery. CT revealed no foreign body residue and colonoscopy showed no metal or other residues in the colon and rectum, and no apparent intestinal tract damage. CONCLUSION: The timeliness and rationality of the surgical and therapeutic options for this patient were based on a literature review of the clinical signs and conceivable conditions in such cases. The type, material and the potential risks of rectal foreign bodies should be considered.

16.
J Hepatol ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38670321

RESUMO

BACKGROUND & AIMS: The precise pathomechanisms underlying the development of nonalcoholic steatohepatitis (NASH, also known as metabolic dysfunction-associated steatohepatitis [MASH]) remain incompletely understood. This study investigates the potential role of EF-hand domain family member D2 (EFHD2), a novel molecule specific to immune cells, in NASH pathogenesis. METHODS: Hepatic EFHD2 expression was characterized in NASH patients and two diet-induced NASH mouse models. Single-cell RNA-sequencing (scRNA-seq) and double-immunohistochemistry were employed to explore EFHD2 expression patterns in NASH livers. The effects of global and myeloid-specific EFHD2 deletion on NASH and NASH-related hepatocellular carcinoma (HCC) were assessed. Molecular mechanisms underlying EFHD2 function were investigated, along with its potential as a therapeutic target by chemical and genetic means. RESULTS: EFHD2 expression was significantly elevated in liver tissue macrophages/monocytes in both NASH patients and mice. Deletion of EFHD2, either globally or specifically in myeloid cells, improved hepatic steatosis, reduced immune cell infiltration, inhibited lipid peroxidation-induced ferroptosis, and attenuated fibrosis in NASH. Additionally, it hindered the development of NASH-related HCC. Specifically, deletion of myeloid EFHD2 prevented the replacement of TIM4+ resident Kupffer cells by infiltrated monocytes and reversed the decreases in patrolling monocytes and CD4+/CD8+ T cell ratio in NASH. Mechanistically, our investigation revealed that EFHD2 in myeloid cells interacts with cytosolic YWHAZ (14-3-3ζ), facilitating the translocation of interferon-γ receptor-2 (IFNγR2) onto the plasma membrane. This interaction mediates IFNγ signaling, which triggers immune and inflammatory responses in macrophages during NASH. Finally, a developed stapled α-helical peptide targeting EFHD2 demonstrated its efficacy in protecting against NASH pathology in mice. CONCLUSION: Our study reveals a pivotal immunomodulatory and inflammatory role of EFHD2 in NASH, underscoring EFHD2 as a promising druggable target for NASH treatment. IMPACT AND IMPLICATIONS: Nonalcoholic steatohepatitis (NASH) represents an advanced stage of non-alcoholic fatty liver disease (NAFLD); however, not all NAFLD patients progress to NASH. A key challenge is identifying the factors triggering inflammation, which propels the transition from simple fatty liver to NASH. Our research pinpointed EFHD2 as a pivotal driver of NASH, orchestrating the over-activation of IFNγ signaling within the liver during NASH progression. A stapled peptide designed to target EFHD2 exhibited therapeutic promise in NASH mice. These findings suggest EFHD2 as a promising target for drug development aimed at NASH treatment.

18.
Int J Pharm ; 657: 124160, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38663642

RESUMO

Addressing the pervasive issue of bacteria and biofilm infections is crucial in the development of advanced antifouling wound dressings. In this study, a novel wound healing treatment using sulfobetaine (SBMA) decorated electrospun fibrous membrane based on polycaprolactone (PCL)/nitric oxide (NO) donors was developed. The fabrication involved a dual strategy, first integrating NO donors into mesoporous polydopamine (MPDA) and complexed with PCL/PEI to electrospin nanofibers. The fibrous membrane exhibited a potent antibacterial response upon irradiation at 808 nm, owing to a combination of NO and photothermal effect that effectively targets bacteria and disrupts biofilms. Surface functionalization of the membrane with PEI allowed for the attachment of SBMA via Michael addition, fabricating a zwitterionic surface, which significantly hinders protein adsorption and reduces biofilm formation on the wound dressing. In vitro and in vivo assessments confirmed the rapid bactericidal capabilities and its efficacy in biofilm eradication. Combining photothermal activity, targeted NO release and antifouling surface, this multifaceted wound dressing addresses key challenges in bacterial infection management and biofilm eradication, promoting efficient wound healing.

19.
Sci Rep ; 14(1): 9511, 2024 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664449

RESUMO

It is important to study the bacteria that cause endometritis to identify effective therapeutic drugs for dairy cows. In this study, 20% oxytetracycline was used to treat Holstein cows (n = 6) with severe endometritis. Additional 10 Holstein cows (5 for healthy cows, 5 for cows with mild endometritis) were also selected. At the same time, changes in bacterial communities were monitored by high-throughput sequencing. The results show that Escherichia coli, Staphylococcus aureus and other common pathogenic bacteria could be detected by traditional methods in cows both with and without endometritis. However, 16S sequencing results show that changes in the abundance of these bacteria were not significant. Endometritis is often caused by mixed infections in the uterus. Oxytetracycline did not completely remove existing bacteria. However, oxytetracycline could effectively inhibit endometritis and had a significant inhibitory effect on the genera Bacteroides, Trueperella, Peptoniphilus, Parvimonas, Porphyromonas, and Fusobacterium but had no significant inhibitory effect on the bacterial genera Marinospirillum, Erysipelothrix, and Enteractinococcus. During oxytetracycline treatment, the cell motility, endocrine system, exogenous system, glycan biosynthesis and metabolism, lipid metabolism, metabolism of terpenoids, polyketides, cofactors and vitamins, signal transduction, and transport and catabolism pathways were affected.


Assuntos
Antibacterianos , Endometrite , Oxitetraciclina , Útero , Oxitetraciclina/farmacologia , Oxitetraciclina/uso terapêutico , Animais , Feminino , Bovinos , Endometrite/microbiologia , Endometrite/veterinária , Endometrite/tratamento farmacológico , Útero/microbiologia , Útero/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias/efeitos dos fármacos , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Doenças dos Bovinos/microbiologia , Doenças dos Bovinos/tratamento farmacológico , RNA Ribossômico 16S/genética , Microbiota/efeitos dos fármacos
20.
Aging Cell ; : e14159, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38556842

RESUMO

Previous research on sleep and aging largely has failed to illustrate the optimal dose-response curve of this relationship. We aimed to analyze the associations between sleep duration and measures of predicted age. In total, 241,713 participants from the UK Biobank were included. Habitual sleep duration was collected from the baseline questionnaire. Four indicators, homeostatic dysregulation (HD), phenoAge (PA), Klemera-Doubal method (KDM), and allostatic load (AL), were chosen to assess predicted age. Multivariate linear regression models were utilized. The association of sleep duration and predicted age followed a U-shape (All p for nonlinear <0.05). Compared with individuals who sleep for 7 h/day, the multivariable-adjusted beta of ≤5 and ≥9 h/day were 0.05 (95% CI 0.03, 0.07) and 0.03 (95% CI 0.02, 0.05) for HD, 0.08 (95% CI 0.01, 0.14) and 0.36 (95% CI 0.31, 0.41) for PA, and 0.21 (95% CI 0.12, 0.30) and 0.30 (95% CI 0.23, 0.37) for KDM. Significant independent and joint effects of sleep and cystatin C (CysC) and gamma glutamyltransferase (GGT) on predicted age metrics were future found. Similar results were observed when conducting stratification analyses. Short and long sleep duration were associated with accelerated predicted age metrics mediated by CysC and GGT.

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