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1.
ACS Sens ; 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38382073

RESUMO

Current microflow cytometers suffer from complicated fluidic integration and low fluorescence collection efficiency, resulting in reduced portability and sensitivity. Herein, we demonstrated a new flow cell design based on an on-chip monolithically integrated microreflector with a bulk acoustic wave resonator (MBAW). It enables simultaneous 3D particle focusing and fluorescence enhancement without using shear flow. Benefited by the on-chip microreflector, the captured fluorescence intensity was 1.8-fold greater than that of the Si substrate and 8.3-fold greater than that of the SiO2 substrate, greatly improving the detection sensitivity. Combined with the contactless acoustic streaming-based focusing, particle sensing with a coefficient of variation as low as 6.1% was achieved. We also demonstrated the difference between live and dead cells and performed a cell cycle assay using the as-developed microflow cytometry. This monolithic integrated MBAW provides a new type of opto-acoustofluidic system and has the potential to be a highly integrated, highly sensitive flow cytometer for applications such as in vitro diagnostics and point of care.

2.
Fitoterapia ; : 105867, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38382891

RESUMO

The concept of multi-target-directed ligands offers fresh perspectives for the creation of brand-new Alzheimer's disease medications. To explore their potential as multi-targeted anti-Alzheimer's drugs, eighteen new bakuchiol derivatives were designed, synthesized, and evaluated. The structures of the new compounds were elucidated by IR, NMR, and HRMS. Eighteen compounds were assayed for acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in vitro using Ellman's method. It was shown that most of the compounds inhibited AChE and BuChE to varying degrees, but the inhibitory effect on AChE was relatively strong, with fourteen compounds showing inhibition of >50% at the concentration of 200 µM. Among them, compound 3g (IC50 = 32.07 ±â€¯2.00 µM) and compound 3n (IC50 = 34.78 ±â€¯0.34 µM) showed potent AChE inhibitory activities. Molecular docking studies and molecular dynamics simulation showed that compound 3g interacts with key amino acids at the catalytically active site (CAS) and peripheral anionic site (PAS) of acetylcholinesterase and binds stably to acetylcholinesterase. On the other hand, compounds 3n and 3q significantly reduced the pro-inflammatory cytokines TNF-α and IL-6 released from LPS-induced RAW 264.7 macrophages. Compound 3n possessed both anti-acetylcholinesterase activity and anti-inflammatory properties. Therefore, an in-depth study of compound 3n is expected to be a multi-targeted anti-AD drug.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38386145

RESUMO

Yeast extract serves as a source of nutritional components essential for human dietary requirements, feed formulations, and the vital growth factors and nutrients necessary for microorganisms. However, the production cost of yeast extract using cultivated active dry yeast is relatively high. This study aims to utilize the autolysis of discarded yeast post beer brewing to produce yeast extract. The concentration, temperature, pH, and time conditions are systematically optimized. It reveals that the yield of amino nitrogen and solids in the extract was increased by 3.3% and 20.9% under the optimized conditions (1.2% wall-breaking enzyme, 1% yeast extract enzyme, and a hydrolysis time of 24 h) than that of the documented 4.03% and 69.05%. Additionally, a comparative analysis with commercially available yeast powder demonstrates that the yeast extract derived from this study adequately fulfills the nutritional requirements for microbial growth. Hence, the utilization of discarded beer yeast presents an opportunity for the valuable reclamation of waste yeast, showcasing promising potential applications.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38379235

RESUMO

This article designs a new hierarchical distributed data-driven adaptive learning control algorithm to accomplish the leader-following tracking control objective for nonaffine nonlinear multiagent systems (MASs). The proposed hierarchical control structure is composed of a distributed observer and a decentralized data-driven adaptive learning controller. Considering that some followers cannot directly receive information from the leader, a distributed observer is designed to estimate the information of the leader. Based on this, a decentralized data-driven adaptive learning controller is further devised to enable the follower to track the estimated information of the leader, where the model parameter learning algorithm is developed to capture the dynamic characteristics of the original system. One advantage of the developed hierarchical control learning algorithm is that neither the leader's system model nor the follower's system model is needed. The other one is the elimination of the noncausal problem without the additional assumption. Simulation results exemplify the merits of the theoretical results by comparisons.

7.
Pest Manag Sci ; 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38380740

RESUMO

BACKGROUND: With the increasing incidence of pest resistance to transgenic crops producing Bacillus thuringiensis (Bt) proteins in the field, elucidating the molecular basis of resistance is important for monitoring, delaying, and countering pest resistance. Previous work revealed that mutation or downregulated expression of the cadherin gene (PgCad1) is associated with pink bollworm (Pectinophora gossypiella) resistance to Cry1Ac, and twenty mutant PgCad1 alleles (r1-r20) were characterized. Here, we tested the hypothesis that the ABC transporter PgABCC2 is a functional receptor for the Bt toxin Cry1Ac and that a mutation is associated with resistance. RESULTS: We identified and characterized the first resistance allele (rC2 ) of PgABCC2 in the laboratory-selected Cry1Ac resistant strain AQ-C2 of pink bollworm. The rC2 allele had a one-base deletion in exon20, resulting in a frameshift and the introduction of a premature stop codon. This resulting PgABCC2 protein had a truncated C-terminus, including the loss of the NBD2 domain. AQ-C2 exhibited 20.2-fold greater resistance to Cry1Ac than the susceptible strain, and its inheritance of Cry1Ac resistance was recessive and genetically linked to PgABCC2. When produced in cultured insect cells, recombinant wildtype and rC2 mutant PgABCC2 proteins localized within the cell plasma membrane, although substantial cytoplasmic retention was also observed for the mutant protein, while the mutant PgABCC2 caused a 13.9-fold decrease in Cry1Ac toxicity versus the wildtype PgABCC2. CONCLUSIONS: PgABCC2 is a functional receptor of Cry1Ac and the loss of its carboxyl terminus (including its NBD2 domain) confers low-level resistance to Cry1Ac in both larvae and in cultured cells.

8.
Phys Med Biol ; 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38373347

RESUMO

OBJECTIVE: Accurate delineation of organs-at-risk (OARs) is a critical step in radiotherapy. The deep learning generated segmentations usually need to be reviewed and corrected by oncologists manually, which is time-consuming and operator-dependent. Therefore, an automated quality assurance (QA) and adaptive optimization correction strategy was proposed to identify and optimize "incorrect" auto-segmentations. APPROACH: A total of 586 CT images and labels from nine institutions were used. The OARs included the brainstem, parotid, and mandible. The deep learning generated contours were compared with the manual ground truth delineations. In this study, we proposed a novel Contour Quality Assurance and Adaptive Optimization (CQA-AO) strategy, which consists of the following three main components: 1) The contour QA module classified the deep learning generated contours as either accepted or unaccepted; 2) The unacceptable contour categories analysis module provided the potential error reasons (five unacceptable category) and locations (attention heatmaps); 3) The adaptive correction of unacceptable contours module integrate vision-language representations and utilize convex optimization algorithms to achieve adaptive correction of "incorrect" contours. MAIN RESULTS: In the contour quality assurance tasks, the sensitivity (accuracy, precision) of CQA-AO strategy reached 0.940 (0.945, 0.948), 0.962 (0.937, 0.913), and 0.967 (0.962, 0.957) for brainstem, parotid and mandible, respectively. The unacceptable contour category analysis, the (F_I,〖Acc〗_I,F_micro,F_macro) of CQA-AO strategy reached (0.901,0.763,0.862,0.822), (0.855,0.737, 0.837, 0.784), and (0.907, 0.762, 0.858, 0.821) for brainstem, parotid and mandible, respectively. After adaptive optimization correction, the DSC values of brainstem, parotid and mandible have been improved by 9.4%, 25.9%, and 13.5%, and HD values decreased by 62%, 70.6%, and 81.6%, respectively. SIGNIFICANCE: The proposed CQA-AO strategy, which combines quality assurance of contour and adaptive optimization correction for OARs contouring, demonstrated superior performance compare to conventional methods. This method can be implemented in the clinical contouring procedures and improve the efficiency of delineating and reviewing workflow.

9.
Oral Dis ; 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38376115

RESUMO

OBJECTIVES: To investigate the inhibitory effects of STM2457, which is a novel METTL3 (m6 A writer) inhibitor, both as a monotherapy and in combination with anlotinib, in the treatment of oral squamous cell carcinoma (OSCC) both in vitro and in vivo. MATERIALS AND METHODS: The efficacy of STM2457 or STM2457 plus anlotinib was evaluated using two OSCC cell lines by CCK8, transwell, colony formation, would-healing, sphere formation, cell cycle, apoptosis assays, and nude mice tumor xenograft techniques. The molecular mechanism study was carried out by western blotting, qRT-PCR, MeRIP-qPCR, immunofluorescence, and immunohistochemistry. RESULTS: STM2457 combined with anlotinib enhanced inhibition of cellular survival/proliferation and promotion of apoptosis in vitro. Moreover, this combinatorial approach exerted a notable reduction in stemness properties and EMT (epithelial-mesenchymal transition) features of OSCC cells. Remarkably, in vivo studies validated the efficacy of the combination treatment. Mechanistically, our investigations revealed that the combined action of STM2457 and anlotinib exerted downregulatory effects on EGFR (epidermal growth factor receptor) expression in OSCC cells. CONCLUSIONS: The combination of STM2457 and anlotinib targeting EGFR exerted a multiple anti-tumor effect. In near future, anlotinib combined with STM2457 may provide a novel insight for the treatment of OSCC.

10.
J Cancer Res Clin Oncol ; 150(2): 95, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38369555

RESUMO

PURPOSE: There is no approved targeted therapy for chordoma at present. Although several preclinical studies have implied the potential applicability of CDK4/6 inhibitor for this rare tumor, no clinical evidence has been documented so far. The purpose of this study was to elucidate the therapeutic efficacy of CDK4/6 inhibitor for chordoma. METHODS: The next generation sequencing (as for whole-exome sequencing, WES assay) and immunohistochemical (IHC) staining of the chordoma tissue from a patient with an advanced lesion were performed before treatment. Then, the patient was treated with Palbociclib for 4 months until progression occurred in the 5th month. Surgical resection was implemented and the tumor tissue was obtained postoperatively for assessment of molecular alterations. RESULTS: Molecular features of the tumor before medical treatment suggested applicability of CDK4/6 inhibitor and the patient showed partial response (PR) according to Choi Criteria after 4 months treating with Palbociclib until progression occurred. Then, a drastic molecular alteration of the tumor as represented by emergence of dramatic E2F amplification, which is known to induce CDK4/6 independent cell-cycle entry and progression after treatment, was detected. The findings in this patient demonstrated tumor evolution under drug pressure. CONCLUSION: The findings of the present study suggest the feasibility of Palbociclib for the clinical treatment of chordoma, and imply the necessity of combination therapies rather single drug administration due to the quick resistance of the tumor to Palbociclib treatment.


Assuntos
Cordoma , Piperazinas , Humanos , Estudos Retrospectivos , Cordoma/tratamento farmacológico , Cordoma/genética , Cordoma/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Piridinas , Quinase 4 Dependente de Ciclina/genética , Inibidores de Proteínas Quinases/farmacologia
11.
Biotechnol J ; 19(2): e2300410, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38375559

RESUMO

Site-specific integration (SSI) via recombinase mediated cassette exchange (RMCE) has shown advantages over random integration methods for expression of biotherapeutics. As an extension of our previous work developing SSI host cells, we developed a dual-site SSI system having two independent integration sites at different genomic loci, each containing a unique landing pad (LP). This system was leveraged to generate and compare two RMCE hosts, one (dFRT) compatible with the Flp recombinase, the other (dBxb1) compatible with the Bxb1 recombinase. Our comparison demonstrated that the dBxb1 host was able to generate stable transfectant pools in a shorter time frame, and cells within the dBxb1 transfectant pools were more phenotypically and genotypically stable. We further improved process performance of the dBxb1 host, resulting in desired fed batch performance attributes. Clones derived from this improved host (referred as 41L-11) maintained stable expression profiles over extended generations. While the data represents a significant improvement in the efficiency of our cell line development process, the dual LP architecture also affords a high degree of flexibility for development of complex protein modalities.


Assuntos
Genômica , Recombinases , Cricetinae , Animais , Células CHO , Cricetulus , Recombinases/genética , Células Clonais/metabolismo , Genômica/métodos , Transgenes
12.
J Gene Med ; 26(2): e3676, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38362844

RESUMO

BACKGROUND: Preeclampsia, a severe pregnancy syndrome, is widely accepted divided into early- and late-onset preeclampsia (EOPE and LOPE) based on the onset time of preeclampsia, with distinct pathophysiological origins. However, the molecular mechanism especially immune-related mechanisms for EOPE and LOPE is currently obscure. In the present study, we focused on placental immune alterations between EOPE and LOPE and search for immune-related biomarkers that could potentially serve as potential therapeutic targets through bioinformatic analysis. METHODS: The gene expression profiling data was obtained from the Gene Expression Omnibus database. ESTIMATE algorithm and Gene Set Enrichment Analysis were employed to evaluate the immune status. The intersection of differentially expressed genes in GSE74341 series and immune-related genes set screened differentially expressed immune-related genes. Protein-protein interaction network and random forest were used to identify hub genes with a validation by a quantitative real-time PCR. Kyoto Encyclopedia of Genes and Genomes pathways, Gene Ontology and gene set variation analysis were utilized to conduct biological function and pathway enrichment analyses. Single-sample gene set enrichment analysis and CIBERSORTx tools were employed to calculate the immune cell infiltration score. Correlation analyses were evaluated by Pearson correlation analysis. Hub genes-miRNA network was performed by the NetworkAnalyst online tool. RESULTS: Immune score and stromal score were all lower in EOPE samples. The immune system-related gene set was significantly downregulated in EOPE compared to LOPE samples. Four hub differentially expressed immune-related genes (IL15, GZMB, IL1B and CXCL12) were identified based on a protein-protein interaction network and random forest. Quantitative real-time polymerase chain reaction validated the lower expression levels of four hub genes in EOPE compared to LOPE samples. Immune cell infiltration analysis found that innate and adaptive immune cells were apparent lacking in EOPE samples compared to LOPE samples. Cytokine-cytokine receptor, para-inflammation, major histocompatibility complex class I and T cell co-stimulation pathways were significantly deficient and highly correlated with hub genes. We constructed a hub genes-miRNA regulatory network, revealing the correlation between hub genes and hsa-miR-374a-5p, hsa-miR-203a-3p, hsa-miR-128-3p, hsa-miR-155-3p, hsa-miR-129-2-3p and hsa-miR-7-5p. CONCLUSIONS: The innate and adaptive immune systems were severely impaired in placentas of EOPE. Four immune-related genes (IL15, GZMB, IL1B and CXCL12) were closely correlated with immune-related pathogenesis of EOPE. The result of our study may provide a new basis for discriminating between EOPE and LOPE and acknowledging the role of the immune landscape in the eventual interference and tailored treatment of EOPE.


Assuntos
Amarelo de Eosina-(YS)/análogos & derivados , MicroRNAs , Fosfatidiletanolaminas , Pré-Eclâmpsia , Gravidez , Humanos , Feminino , Pré-Eclâmpsia/etiologia , Placenta/metabolismo , Interleucina-15/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Biomarcadores/metabolismo
13.
Sci Adv ; 10(7): eadk1721, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363834

RESUMO

Characterizing the tumor microenvironment at the molecular level is essential for understanding the mechanisms of tumorigenesis and evolution. However, the specificity of the blood proteome in localized region of the tumor and its linkages with other systems is difficult to investigate. Here, we propose a spatially multidimensional comparative proteomics strategy using glioma as an example. The blood proteome signature of tumor microenvironment was specifically identified by in situ collection of arterial and venous blood from the glioma region of the brain for comparison with peripheral blood. Also, by integrating with different dimensions of tissue and peripheral blood proteomics, the information on the genesis, migration, and exchange of glioma-associated proteins was revealed, which provided a powerful method for tumor mechanism research and biomarker discovery. The study recruited multidimensional clinical cohorts, allowing the proteomic results to corroborate each other, reliably revealing biological processes specific to gliomas, and identifying highly accurate biomarkers.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Proteômica/métodos , Neoplasias Encefálicas/patologia , Proteoma/metabolismo , Glioma/patologia , Biomarcadores , Microambiente Tumoral
14.
Carbohydr Polym ; 330: 121812, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38368083

RESUMO

Biomacromolecules based injectable and self-healing hydrogels possessing high mechanical properties have widespread potential in biomedical field. However, dynamic features are usually inversely proportional to toughness. It is challenging to simultaneously endow these properties to the dynamic hydrogels. Here, we fabricated an injectable nanocomposite hydrogel (CS-NPs@OSA-l-Gtn) stimultaneously possessing excellent autonomous self-healing performance and high mechanical strength by doping chitosan nanoparticles (CS-NPs) into dynamic polymer networks of oxidized sodium alginate (OSA) and gelatin (Gtn) in the presence of borax. The synergistic effect of the multiple reversible interactions combining dynamic covalent bonds (i.e., imine bond and borate ester bond) and noncovalent interactions (i.e., electrostatic interaction and hydrogen bond) provide effective energy dissipation to endure high fatigue resistance and cyclic loading. The dynamic hydrogel exhibited excellent mechanical properties like maximum 2.43 MPa compressive strength, 493.91 % fracture strain, and 89.54 kJ/m3 toughness. Moreover, the integrated hydrogel after injection and self-healing could withstand 150 successive compressive cycles. Besides, the bovine serum albumin embedded in CS-NPs could be sustainably released from the nanocomposite hydrogel for 12 days. This study proposes a novel strategy to synthesize an injectable and self-healing hydrogel combined with excellent mechanical properties for designing high-strength natural carriers with sustained protein delivery.


Assuntos
Alginatos , Quitosana , Alginatos/química , Nanogéis , Gelatina/química , Hidrogéis/química , Polímeros , Quitosana/química
15.
Biochem Pharmacol ; 222: 116066, 2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38373592

RESUMO

Chimeric antigen receptor (CAR)-immune cell therapy has revolutionized the anti-tumor field, achieving efficient and precise tumor clearance by directly guiding immune cell activity to target tumors. In addition, the use of CAR-immune cells to influence the composition and function of the immune system and ultimately achieve virus clearance and immune system homeostasis has attracted the interest of researchers. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered a global pandemic of coronavirus disease 2019 (COVID-19). To date, the rapidly mutating SARS-CoV-2 continues to challenge existing therapies and has raised public concerns regarding reinfection. In patients with COVID-19, the interaction of SARS-CoV-2 with the immune system influences the course of the disease, and the coexistence of over-activated immune system components, such as macrophages, and severely compromised immune system components, such as natural killer cells, reveals a dysregulated immune system. Dysregulated immune-induced inflammation may impair viral clearance and T-cell responses, causing cytokine storms and ultimately leading to patient death. Here, we summarize the research progress on the use of CAR-immune cells against SARS-CoV-2 infection. Furthermore, we discuss the feasibility, challenges and prospect of CAR-immune cells as a new immune candidate therapy against SARS-CoV-2.

16.
ACS Chem Neurosci ; 15(4): 808-815, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38315060

RESUMO

Silica nanoparticles (SiO2 NPs) are widely used engineered materials that warrant their obvious environmental exposure risk. Our previous study has shown that different routes of SiO2 NP exposure on the glycogen synthase kinase 3 beta (GSK3ß) activity were related to the serum proteins enriched on the surface of SiO2 NPs, which implied that a particular protein in the serum changed the inherent toxic behavior of SiO2 NPs and inhibited the activation of GSK3ß by SiO2 NPs. Here, we identified that the SiO2 NP surface enriched a large amount of apolipoprotein E (ApoE), and the ApoE protein corona bound to the lipoprotein receptor-related protein 1 (LRP1) to inactivate GSK3ß, thereby reducing the damage of SiO2 NPs to the brain. This work presented the first evidence that specific biocorona reduced the toxicity of SiO2 NPs at the molecular level, which helped to elucidate the role of specific corona components on nanotoxicity.


Assuntos
Nanopartículas , Doenças do Sistema Nervoso , Humanos , Dióxido de Silício/toxicidade , Glicogênio Sintase Quinase 3 beta , Apolipoproteínas E/genética , Apolipoproteínas , Fatores de Transcrição , Nanopartículas/toxicidade , Encéfalo , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade
17.
Chem Commun (Camb) ; 60(17): 2373-2376, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38318933

RESUMO

This work reports the construction of a miniaturized Ag/AgCl nanoelectrode on a nanopipette, which is capable of dual-functions of single-cell drug infusion and chloride detection and is envisioned to promote the study of chloride-correlated therapeutic effects.

18.
Phys Med Biol ; 69(5)2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38306968

RESUMO

Objective. Radiation therapy (RT) represents a prevalent therapeutic modality for head and neck (H&N) cancer. A crucial phase in RT planning involves the precise delineation of organs-at-risks (OARs), employing computed tomography (CT) scans. Nevertheless, the manual delineation of OARs is a labor-intensive process, necessitating individual scrutiny of each CT image slice, not to mention that a standard CT scan comprises hundreds of such slices. Furthermore, there is a significant domain shift between different institutions' H&N data, which makes traditional semi-supervised learning strategies susceptible to confirmation bias. Therefore, effectively using unlabeled datasets to support annotated datasets for model training has become a critical issue for preventing domain shift and confirmation bias.Approach. In this work, we proposed an innovative cross-domain orthogon-based-perspective consistency (CD-OPC) strategy within a two-branch collaborative training framework, which compels the two sub-networks to acquire valuable features from unrelated perspectives. More specifically, a novel generative pretext task cross-domain prediction (CDP) was designed for learning inherent properties of CT images. Then this prior knowledge was utilized to promote the independent learning of distinct features by the two sub-networks from identical inputs, thereby enhancing the perceptual capabilities of the sub-networks through orthogon-based pseudo-labeling knowledge transfer.Main results. Our CD-OPC model was trained on H&N datasets from nine different institutions, and validated on the four local intuitions' H&N datasets. Among all datasets CD-OPC achieved more advanced performance than other semi-supervised semantic segmentation algorithms.Significance. The CD-OPC method successfully mitigates domain shift and prevents network collapse. In addition, it enhances the network's perceptual abilities, and generates more reliable predictions, thereby further addressing the confirmation bias issue.


Assuntos
Aprendizado Profundo , Neoplasias de Cabeça e Pescoço , Humanos , Semântica , Tomografia Computadorizada por Raios X , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/radioterapia , Órgãos em Risco , Processamento de Imagem Assistida por Computador/métodos
19.
Am J Pathol ; 2024 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-38320628

RESUMO

Psoriasis is a chronic inflammatory skin disease characterized by the activation of keratinocytes and the infiltration of immune cells. Overexpression of the transcription factor LIM-domain only protein 4 (LMO4) promoted by IL-23 has critical roles in regulating the proliferation and differentiation of psoriatic keratinocytes. IL-6, an autocrine cytokine in psoriatic epidermis, is a key mediator of IL-23/T helper 17-driven cutaneous inflammation. However, little is known about how IL-6 regulates the up-regulation of LMO4 expression in psoriatic lesions. In this study, human immortalized keratinocyte cells, clinical biopsy specimens, and an animal model of psoriasis induced by imiquimod cream were used to investigate the role of IL-6 in the regulation of keratinocyte proliferation and differentiation. In this study, IL-6 and LMO4 were expressed abnormally in the psoriatic epidermis. IL-6 up-regulates the expression of LMO4 and promotes keratinocyte proliferation and differentiation. Furthermore, in vitro and in vivo studies have shown that IL-6 up-regulates LMO4 expression by activating the MEK/ERK/NF-κB signaling pathway. These results suggest that IL-6 can activate the NF-κB signaling pathway, up-regulate the expression of LMO4, lead to abnormal proliferation and differentiation of keratinocytes, and promote the occurrence and development of psoriasis.

20.
Opt Lett ; 49(4): 911-914, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38359214

RESUMO

In this Letter, a method for the fabrication of bifocal lenses is presented by combining surface ablation and bulk modification in a single laser exposure followed by the wet etching processing step. The intensity of a single femtosecond laser pulse was modulated axially into two foci with a designed computer-generated hologram (CGH). Such pulse simultaneously induced an ablation region on the surface and a modified volume inside the fused silica. After etching in hydrofluoric acid (HF), the two exposed regions evolved into a bifocal lens. The area ratio (diameter) of the two lenses can be flexibly adjusted via control of the pulse energy distribution through the CGH. Besides, bifocal lenses with a center offset as well as convex lenses were obtained by a replication technique. This method simplifies the fabrication of micro-optical elements and opens a highly efficient and simple pathway for complex optical surfaces and integrated imaging systems.

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