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1.
Biomaterials ; 312: 122749, 2025 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-39121725

RESUMEN

The prevalence of Alzheimer's disease (AD) is increasing globally due to population aging. However, effective clinical treatment strategies for AD still remain elusive. The mechanisms underlying AD onset and the interplay between its pathological factors have so far been unclear. Evidence indicates that AD progression is ultimately driven by neuronal loss, which in turn is caused by neuroapoptosis and neuroinflammation. Therefore, the inhibition of neuroapoptosis and neuroinflammation could be a useful anti-AD strategy. Nonetheless, the delivery of active drug agents into the brain parenchyma is hindered by the blood-brain barrier (BBB). To address this challenge, we fabricated a black phosphorus nanosheet (BP)-based methylene blue (MB) delivery system (BP-MB) for AD therapy. After confirming the successful preparation of BP-MB, we proved that its BBB-crossing ability was enhanced under near-infrared light irradiation. In vitro pharmacodynamics analysis revealed that BP and MB could synergistically scavenge excessive reactive oxygen species (ROS) in okadaic acid (OA)-treated PC12 cells and lipopolysaccharide (LPS)-treated BV2 cells, thus efficiently reversing neuroapoptosis and neuroinflammation. To study in vivo pharmacodynamics, we established a mouse model of AD mice, and behavioral tests confirmed that BP-MB treatment could successfully improve cognitive function in these animals. Notably, the results of pathological evaluation were consistent with those of the in vitro assays. The findings demonstrated that BP-MB could scavenge excessive ROS and inhibit Tau hyperphosphorylation, thereby alleviating downstream neuroapoptosis and regulating the polarization of microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. Overall, this study highlights the therapeutic potential of a smart nanomedicine with the capability of reversing neuroapoptosis and neuroinflammation for AD treatment.


Asunto(s)
Enfermedad de Alzheimer , Apoptosis , Barrera Hematoencefálica , Azul de Metileno , Nanomedicina , Enfermedades Neuroinflamatorias , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/patología , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Apoptosis/efectos de los fármacos , Células PC12 , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Ratas , Ratones , Nanomedicina/métodos , Azul de Metileno/farmacología , Azul de Metileno/uso terapéutico , Masculino , Especies Reactivas de Oxígeno/metabolismo , Ratones Endogámicos C57BL
2.
Skin Res Technol ; 30(9): e13906, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39300828

RESUMEN

BACKGROUND: The genetic association between urticaria and mental disorders and whether inflammatory cytokines mediate this process remains unclear. MATERIALS AND METHODS: A Mendelian randomization (MR) approaches to elucidate the causal relationship between urticaria and mental disorders and to validate the mediation of inflammatory cytokines. Genome-wide association study (GWAS) databases used were obtained from Psychiatric Genomics Cooperation (PGC), GWAS Catalog, and FinnGen Consortium. Our study was conducted using inverse variance weighted (IVW) and Bayesian weighted MR (BWMR) methods for joint analysis. RESULTS: The MR results showed that urticaria increased the risk of attention deficit hyperactivity disorder (ADHD) (odds ratio [OR] = $ = $ 1.088, 95% confidence interval [CI]: 1.026-1.154, p = $ = $ 0.0051); cholinergic urticaria increased the risk of bipolar disorder (BD) (OR = $ = $ 1.012, 95% CI: 1.001-1.022, p = $ = $ 0.0274); dermatographic urticaria increased the risk of ADHD (OR = $ = $ 1.057, 95% CI: 1.005-1.112, p = $ = $ 0.0323); idiopathic urticaria increased the risk of schizophrenia (SCZ) (OR = $ = $ 1.057, 95% CI: 1.005-1.112, p = $ = $ 0.0323); other unspecified urticaria increased the risk of ADHD (OR = $ = $ 1.085, 95% CI: 1.023-1.151, p = $ = $ 0.0063). We found that eight inflammatory cytokines were negatively associated with mental disorders and seven inflammatory cytokines were positively associated with mental disorders. Finally, our results suggested that inflammatory cytokines do not act as mediators between urticaria and mental disorders. CONCLUSIONS: Our study reveals a causal relationship between urticaria and the increased risk of mental disorders. We suggest that the treatment of urticaria could incorporate psychiatric interventions and mental health assessment of patients.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Citocinas , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Trastornos Mentales , Urticaria , Humanos , Citocinas/genética , Urticaria/genética , Trastornos Mentales/genética , Trastornos Mentales/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/genética , Predisposición Genética a la Enfermedad/genética , Trastorno Bipolar/genética , Polimorfismo de Nucleótido Simple
3.
Theranostics ; 14(13): 5152-5183, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39267776

RESUMEN

The therapeutic efficacy of drugs is determined, to a certain extent, by the efficiency of drug delivery. The low efficiency of drug delivery systems (DDSs) is frequently associated with serious toxic side effects and can even prove fatal in certain cases. With the rapid development of technology, drug delivery has evolved from using traditional frameworks to using nano DDSs (NDDSs), endogenous biomaterials DDSs (EBDDSs), and living cell DDSs (LCDDSs). LCDDSs are receiving widespread attention from researchers at present owing to the unique advantages of living cells in targeted drug delivery, including their excellent biocompatibility properties, low immunogenicity, unique biological properties and functions, and role in the treatment of diseases. However, the theoretical basis and techniques involved in the application of LCDDSs have not been extensively summarized to date. Therefore, this review comprehensively summarizes the properties and applications of living cells, elaborates the various drug loading approaches and controlled drug release, and discusses the results of clinical trials. The review also discusses the current shortcomings and prospects for the future development of LCDDSs, which will serve as highly valuable insights for the development and clinical transformation of LCDDSs in the future.


Asunto(s)
Sistemas de Liberación de Medicamentos , Humanos , Sistemas de Liberación de Medicamentos/métodos , Animales , Materiales Biocompatibles , Nanopartículas , Portadores de Fármacos/química
4.
Int Immunopharmacol ; 141: 112956, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39168022

RESUMEN

DNA vaccines are prospective for their efficient manufacturing process, but their immunogenicity is limited as they cannot efficiently induce CD8+ T cell responses. A promising approach is to induce cross-presentation by targeting antigens to DCs. Flt3L can expand the number of type 1 conventional DCs and thereby improve cross-presentation. In this study, we first constructed a DNA vaccine expressing soluble PD1 and found that the therapeutic effect of targeting DCs with only the sPD1 vaccine was limited. When combined the vaccine with Flt3L, the anti-tumor effect was significantly enhanced. Considering the complexity of tumors and that a single method may not be able to activate a large number of effective CD8+ T cells, we combined different drugs and the vaccine with Flt3L based on the characteristics of different tumors. In 4T1 model, we reduced Tregs through cyclophosphamide. In Panc02 model, we increased activated DCs by using aCD40. Both strategies triggered strong CD8+ T cell responses and significantly improved the therapeutic effect. Our study provides important support for the clinical exploration of DC-targeted DNA vaccines in combination with Flt3L.


Asunto(s)
Linfocitos T CD8-positivos , Vacunas contra el Cáncer , Células Dendríticas , Proteínas de la Membrana , Ratones Endogámicos BALB C , Receptor de Muerte Celular Programada 1 , Vacunas de ADN , Vacunas de ADN/inmunología , Animales , Células Dendríticas/inmunología , Receptor de Muerte Celular Programada 1/inmunología , Vacunas contra el Cáncer/inmunología , Linfocitos T CD8-positivos/inmunología , Proteínas de la Membrana/inmunología , Proteínas de la Membrana/genética , Femenino , Ratones , Línea Celular Tumoral , Humanos , Ratones Endogámicos C57BL
5.
Bioresour Technol ; 412: 131375, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39214174

RESUMEN

The functionality of electroactive biofilms (EABs) is profoundly influenced by the proteomic dynamics within microbial communities, particularly through the participation of proteins in electron transfer. This study explored the impact of electrode surface orientation, measured by varying oblique angles, on the performance of EABs in bioelectrochemical systems (BES). Utilizing quantitative proteomics, results indicated that a slightly oblique angle (45°) optimized the spatial arrangement of microbial cells, enhancing electron transport efficiency compared to other angles tested. Specifically, the 45° orientation resulted in a 2.36-fold increase in the abundance of c-type cytochromes compared to the 90°. Additionally, Geobacter, showed a relative abundance of 83.25 % at 45°, correlating with a peak current density of 1.87 ± 0.04 A/m2. These microbial and proteomic adaptations highlighted the intricate balance between microbial behavior and the physical environment, which could be tuned to optimize operations. The findings provided new insights into the design and enhancement of BES.


Asunto(s)
Fuentes de Energía Bioeléctrica , Biopelículas , Electrodos , Geobacter , Proteómica , Biopelículas/crecimiento & desarrollo , Proteómica/métodos , Geobacter/fisiología , Geobacter/metabolismo , Fuentes de Energía Bioeléctrica/microbiología , Transporte de Electrón , Proteínas Bacterianas/metabolismo
6.
Sci Rep ; 14(1): 19429, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39169057

RESUMEN

This study aims at the controllability of acoustically manipulated non-contact aggregation of bi-particle. Based on the acoustic wave radiation model of the transducer and the acoustic wave interference theory, the mathematical model between the spatial levitation point and the phase of the phased array ultrasonic array unit is established. A double-sided phased array test system was developed and the phase calculation algorithm for independently manipulating bi-particle was optimized. The algorithm is capable of independently distributing the energy applied to each levitation point. Through simulation and experiment, the horizontally aggregation characteristics of two levitated particles are investigated, and a interesting relationship between particles aggregation and standing wave phase difference is revealed, which follows the law of "attraction in the same phase but repulsion in the opposite phase". By adjusting the tilt angle of the standing wave acoustic trap, the critical distance when particles to accelerate and collision is sharply reduced from 1.5λ to 0.5λ, which provides a new perspective and potential application path for acoustic manipulation technology.

7.
Angew Chem Int Ed Engl ; : e202411150, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39136333

RESUMEN

The first wide-view image of multiple structural and phase transformations for MOFs from crystal state transformations further to the extreme limit approaching liquid/glass phase, was presented based on a square-layer framework of [Co2(pybz)2(CH3COO)2]·DMF (Co2). The process involves i) an initial crystalline transformation brings to a 3-fold interpenetrated and ordered vacancies contained framework [Co(pybz)2(CH3OH)2]·2CH3OH (CoM) due to in-situ disassemble-reassemble, ii) thermal induced departure of a pair of cis-form coordinated methanol in CoM leads to amorphous framework (a-dCoM), iii) glass transition (Tg = 566 K) to super-cooled liquid (scl-dCoM, spanning 38 K), iv) obtaining MOF glass g-dCoM upon quenching the super-cooled liquid, and v) re-crystallization of super-cooled liquid to six-fold interpenetrated dia-net framework [Co(pybz)2]6n (rec-dCoM) under heating above 604 K. The access to glass from CoM, provides a new self-perturbation strategy to create more MOF glasses without melting. The wider pore size distribution in amorphous/glassy MOFs than crystalline precursor realized the first time selective hydrocarbon gas separation by breakthrough experiments, which bring efficient separation of 1:99 C2H2/C2H4 by either a-dCoM or g-dCoM and produce polymer grade C2H4 with purity ≥ 99.5% after a single adsorption process. Furthermore, the mixture of 50:50 C3H6/C3H8 can be separated by a-dCoM.

8.
Small ; : e2404260, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39105466

RESUMEN

While the formation of an inorganic-rich solid electrolyte interphase (SEI) plays a crucial role, the persistent challenge lies in the formation of an organic-rich SEI due to the high solvent ratio in low-concentration electrolytes (LCEs), which hinders the achievement of high-performance lithium metal batteries. Herein, by incorporating di-fluoroethylene carbonate (DFEC) as a non-solvating cosolvent, a solvation structure dominated by anions is introduced in the innovative LCE, leading to the creation of a durable and stable inorganic-rich SEI. Leveraging this electrolyte design, the Li||NCM83 cell demonstrates exceptional cycling stability, maintaining 82.85% of its capacity over 500 cycles at 1 C. Additionally, Li||NCM83 cell with a low N/P ratio (≈2.57) and reduced electrolyte volume (30 µL) retain 87.58% of its capacity after 150 cycles at 0.5 C. Direct molecular information is utilized to reveal a strong correlation between solvation structures and reduction sequences, proving the anion-dominate solvation structure can impedes the preferential reduction of solvents and constructs an inorganic-rich SEI. These findings shed light on the pivotal role of solvation structures in dictating SEI composition and battery performance, offering valuable insights for the design of advanced electrolytes for next-generation lithium metal batteries.

9.
Angew Chem Int Ed Engl ; : e202412308, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39129646

RESUMEN

Light-driven dry reforming of methane is a promising and mild route to convert two greenhouse gas into valuable syngas. However, developing facile strategy to atomically-precise regulate the active sites and realize balanced and stable syngas production is still challenging. Herein, we developed a spatial confinement approach to precisely control over platinum species on TiO2 surfaces, from single atoms to nanoclusters. The configuration comprising single atoms and sub-nanoclusters engenders pronounced electronic metal-support interactions, with resultant interfacial states prompting surface charge rearrangement. The unique geometric and electronic properties of these atom-cluster assemblies facilitate effective activation of CH4 and CO2, accelerating intermediate coupling and minimizing side reactions. Our catalyst exhibits an outstanding syngas generation rate of 34.41 mol gPt-1 h-1 with superior durability, displaying high apparent quantum yield of 9.1% at 365 nm and turnover frequency of 1289 h-1. This work provides insightful understanding for exploring more multi-molecule systems at an atomic scale.

10.
Acta Biomater ; 186: 229-245, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39038749

RESUMEN

Pathogenic bacteria are closely associated with the occurrence, development and metastasis of oral squamous cell carcinoma (OSCC). Antibacterial therapy has been considered an enhancement strategy to suppress bacteria-associated tumors and promote anti-tumor immune responses. Herein, we developed an injectable adhesive hydrogel, PNIPAM/DL@TIR, for the in situ photothermal ablation and robust stimulation of antitumor immunity against OSCC colonized by Porphyromonas gingivalis (Pg), one of the major oral pathogenic bacteria. PNIPAM/DL@TIR, composed of poly(N-isopropylacrylamide), demethylated lignin, and TAT peptide-conjugated IR820, was prepared using a simple dissolve-dry-swell solvent exchange method. Upon 808 nm laser irradiation, PNIPAM/DL@TIR exerted photothermal effects to ablate Pg-colonized OSCC and generate dual tumor and bacterial antigens. Owing to its large number of catechol groups, PNIPAM/DL@TIR efficiently captured these antigens to form an in situ antigen repository, thereby eliciting robust and durable antitumor immune responses. Proteomic analysis revealed that the captured antigens comprised both tumor neoantigens and bacterial antigens. The catechol groups endowed PNIPAM/DL@TIR with antioxidant activity, which was also conducive to stimulating antitumor immunity. Altogether, this study develops an injectable adhesive hydrogel and provides a combination strategy for treating bacteria-associated OSCC. STATEMENT OF SIGNIFICANCE: In this study, we developed an injectable adhesive hydrogel, PNIPAM/DL@TIR, for in situ photothermal ablation and robust stimulation of antitumor immunity against OSCC colonized by Porphyromonas gingivalis, one of the major oral pathogenic bacteria. PNIPAM/DL@TIR, which consists of poly(N-isopropylacrylamide), demethylated lignin, and TAT peptide-conjugated IR820 exhibited outstanding photothermal performance. Owing to the presence of catechol groups, PNIPAM/DL@TIR has good bioadhesive properties and can capture protein antigens to form in situ antigen repository, thus initiating robust and long-term antitumor immune responses. In addition, PNIPAM/DL@TIR exhibited strong antioxidant activity that is favorable for promoting antitumor immunity. In the mouse model of OSCC with bacterial infection, PNIPAM/DL@TIR not only ablated the primary tumors upon NIR laser irradiation, but also induced tumor and bacterial vaccination in situ to suppress distant tumors and lung metastasis.


Asunto(s)
Hidrogeles , Neoplasias de la Boca , Porphyromonas gingivalis , Animales , Hidrogeles/química , Hidrogeles/farmacología , Neoplasias de la Boca/patología , Neoplasias de la Boca/inmunología , Neoplasias de la Boca/terapia , Ratones , Resinas Acrílicas/química , Resinas Acrílicas/farmacología , Humanos , Línea Celular Tumoral , Terapia Fototérmica/métodos , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/terapia , Ratones Endogámicos BALB C
11.
J Agric Food Chem ; 72(28): 15811-15822, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38975865

RESUMEN

Colanic acid (CA) is exopolysaccharide that presents growing potential in the food and healthcare industry as a versatile polymer. Previously, we have constructed the Escherichia coli strain WWM16 which can efficiently produce CA. In this study, WWM16 has been further engineered to produce a higher yield of CA with low molecular mass and viscosity. The gene mcbR encoding a transcriptional factor, and the genes opgD, opgG, and opgH related to the biosynthesis of osmoregulated periplasmic glucans were deleted in E. coli WWM16, and the resulting strain WWM166 produced 18.1 g/L CA. The expression level of wcaD encoding the polymerase in WWM166 was downregulated using CRISPRi. As a result, the strain WWM166/pWpD1 could produce 49.9 g/L CA with lower molecular mass. CA products were purified from both WWM166 and WWM166/pWpD1, and their molecular mass, viscosity, fluidity, hygroscopicity, and antioxidant activity were determined and compared. These findings demonstrate the potential application of CA with different molecular masses to prolong life and protect skin in the food and cosmetic industries.


Asunto(s)
Escherichia coli , Peso Molecular , Escherichia coli/genética , Escherichia coli/metabolismo , Viscosidad , Ingeniería Metabólica , Polisacáridos/metabolismo , Polisacáridos/química , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/química
12.
Adv Mater ; 36(35): e2407433, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38973089

RESUMEN

Interface-induced nonradiative recombination losses at the perovskite/electron transport layer (ETL) are an impediment to improving the efficiency and stability of inverted (p-i-n) perovskite solar cells (PSCs). Tridecafluorohexane-1-sulfonic acid potassium (TFHSP) is employed as a multifunctional dipole molecule to modify the perovskite surface. The solid coordination and hydrogen bonding efficiently passivate the surface defects, thereby reducing nonradiative recombination. The induced positive dipole layer between the perovskite and ETLs improves the energy band alignment, enhancing interface charge extraction. Additionally, the strong interaction between TFHSP and the perovskite stabilizes the perovskite surface, while the hydrophobic fluorinated moieties prevent the ingress of water and oxygen, enhancing the device stability. The resultant devices achieve a power conversion efficiency (PCE) of 24.6%. The unencapsulated devices retain 91% of their initial efficiency after 1000 h in air with 60% relative humidity, and 95% after 500 h under maximum power point (MPP) tracking at 35 °C. The utilization of multifunctional dipole molecules opens new avenues for high-performance and long-term stable perovskite devices.

13.
Nano Lett ; 24(31): 9598-9607, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-38922640

RESUMEN

Enhancing the antitumor immune response and targeting ability of oncolytic viruses will improve the effect of tumor immunotherapy. Through infecting neural stem cells (NSCs) with a capsid dual-modified oncolytic adenovirus (CRAd), we obtained and characterized the "oncolytic extracellular vesicles" (CRAdEV) with improved targeted infection and tumor killing activity compared with CRAd. Both ex vivo and in vivo studies revealed that CRAdEV activated innate immune cells and importantly enhanced the immunomodulatory effect compared to CRAd. We found that CRAdEV effectively increased the number of DCs and activated CD4+ and CD8+ T cells, significantly increased the number and activation of B cells, and produced higher levels of tumor-specific antibodies, thus eliciting enhanced antitumor activity compared with CRAd in a B16 xenograft immunocompetent mice model. This study provides a novel approach to oncolytic adenovirus modification and demonstrates the potential of "oncolytic extracellular vesicles" in antitumor immunotherapy.


Asunto(s)
Adenoviridae , Vesículas Extracelulares , Viroterapia Oncolítica , Virus Oncolíticos , Animales , Ratones , Adenoviridae/genética , Viroterapia Oncolítica/métodos , Humanos , Línea Celular Tumoral , Inmunoterapia , Células-Madre Neurales/inmunología , Inmunomodulación/efectos de los fármacos , Melanoma Experimental/inmunología , Melanoma Experimental/terapia , Melanoma Experimental/patología , Linfocitos T CD8-positivos/inmunología
14.
J Med Virol ; 96(6): e29769, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38932482

RESUMEN

Integration of the human papillomavirus (HPV) genome into the cellular genome is a key event that leads to constitutive expression of viral oncoprotein E6/E7 and drives the progression of cervical cancer. However, HPV integration patterns differ on a case-by-case basis among related malignancies. Next-generation sequencing technologies still face challenges for interrogating HPV integration sites. In this study, utilizing Nanopore long-read sequencing, we identified 452 and 108 potential integration sites from the cervical cancer cell lines (CaSki and HeLa) and five tissue samples, respectively. Based on long Nanopore chimeric reads, we were able to analyze the methylation status of the HPV long control region (LCR), which controls oncogene E6/E7 expression, and to identify transcriptionally-active integrants among the numerous integrants. As a proof of concept, we identified an active HPV integrant in between RUNX2 and CLIC5 on chromosome 6 in the CaSki cell line, which was supported by ATAC-seq, H3K27Ac ChIP-seq, and RNA-seq analysis. Knockout of the active HPV integrant, by the CRISPR/Cas9 system, dramatically crippled cell proliferation and induced cell senescence. In conclusion, identifying transcriptionally-active HPV integrants with Nanopore sequencing can provide viable targets for gene therapy against HPV-associated cancers.


Asunto(s)
Terapia Genética , Secuenciación de Nanoporos , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Integración Viral , Humanos , Neoplasias del Cuello Uterino/virología , Femenino , Secuenciación de Nanoporos/métodos , Integración Viral/genética , Terapia Genética/métodos , Infecciones por Papillomavirus/virología , Línea Celular Tumoral , Células HeLa , Proteínas Oncogénicas Virales/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Papillomaviridae/genética , Virus del Papiloma Humano
15.
Mucosal Immunol ; 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38866206

RESUMEN

Corneal wound healing in diabetic patients is usually delayed and accompanied by excessive inflammation. However, the underlying cellular and molecular mechanisms remain poorly understood. Here, we found that somatostatin (SST), an immunosuppressive peptide produced by corneal nerve fibers, was significantly reduced in streptozotocin-induced diabetic mice. In addition, we discovered that topical administration of exogenous SST significantly improved re-epithelialization and nerve regeneration following diabetic corneal epithelial abrasion. Further analysis showed that topical SST significantly reduced the expression of injury inflammation-related genes, inhibited neutrophil infiltration, and shifted macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 in diabetic corneas' healing. Moreover, the application of L-817,818, an agonist of the SST receptor type 5 subtype, significantly reduced the inflammatory response following epithelial injury and markedly improved the process of re-epithelialization and nerve regeneration in mice. Taken together, these data suggest that activation of the SST-SST receptor type 5 pathway significantly ameliorates diabetes-induced abnormalities in corneal wound repair in mice. Targeting this pathway may provide a novel strategy to restore impaired corneal wound closure and nerve regeneration in diabetic patients.

16.
Animals (Basel) ; 14(11)2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38891695

RESUMEN

The transcriptome complexity and splicing patterns in male and female cattle are ambiguous, presenting a substantial obstacle to genomic selection programs that seek to improve productivity, disease resistance, and reproduction in cattle. A comparative transcriptomic analysis using Oxford Nanopore Technologies (ONT) was conducted in bovine testes (TESTs), ovaries (OVAs), muscles (MUSCs), and livers (LIVs). An average of 5,144,769 full-length reads were obtained from each sample. The TESTs were found to have the greatest number of alternative polyadenylation (APA) events involved in processes such as sperm flagellum development and fertilization in male reproduction. In total, 438 differentially expressed transcripts (DETs) were identified in the LIVs in a comparison of females vs. males, and 214 DETs were identified in the MUSCs between females and males. Additionally, 14,735, 36,347, and 33,885 DETs were detected in MUSC vs. LIV, MUSC vs. TEST, and OVA vs. TEST comparisons, respectively, revealing the complexity of the TEST. Gene Set Enrichment Analysis (GSEA) showed that these DETs were mainly involved in the "spermatogenesis", "flagellated sperm motility", "spermatid development", "reproduction", "reproductive process", and "microtubule-based movement" KEGG pathways. Additional studies are necessary to further characterize the transcriptome in different cell types, developmental stages, and physiological conditions in bovines and ascertain the functions of the novel transcripts.

17.
Sci Rep ; 14(1): 14208, 2024 06 20.
Artículo en Inglés | MEDLINE | ID: mdl-38902252

RESUMEN

The COVID-19 disease is an ongoing global health concern. Although vaccination provides some protection, people are still susceptible to re-infection. Ostensibly, certain populations or clinical groups may be more vulnerable. Factors causing these differences are unclear and whilst socioeconomic and cultural differences are likely to be important, human genetic factors could influence susceptibility. Experimental studies indicate SARS-CoV-2 uses innate immune suppression as a strategy to speed-up entry and replication into the host cell. Therefore, it is necessary to understand the impact of variants in immunity-associated human proteins on susceptibility to COVID-19. In this work, we analysed missense coding variants in several SARS-CoV-2 proteins and their human protein interactors that could enhance binding affinity to SARS-CoV-2. We curated a dataset of 19 SARS-CoV-2: human protein 3D-complexes, from the experimentally determined structures in the Protein Data Bank and models built using AlphaFold2-multimer, and analysed the impact of missense variants occurring in the protein-protein interface region. We analysed 468 missense variants from human proteins and 212 variants from SARS-CoV-2 proteins and computationally predicted their impacts on binding affinities for the human viral protein complexes. We predicted a total of 26 affinity-enhancing variants from 13 human proteins implicated in increased binding affinity to SARS-CoV-2. These include key-immunity associated genes (TOMM70, ISG15, IFIH1, IFIT2, RPS3, PALS1, NUP98, AXL, ARF6, TRIMM, TRIM25) as well as important spike receptors (KREMEN1, AXL and ACE2). We report both common (e.g., Y13N in IFIH1) and rare variants in these proteins and discuss their likely structural and functional impact, using information on known and predicted functional sites. Potential mechanisms associated with immune suppression implicated by these variants are discussed. Occurrence of certain predicted affinity-enhancing variants should be monitored as they could lead to increased susceptibility and reduced immune response to SARS-CoV-2 infection in individuals/populations carrying them. Our analyses aid in understanding the potential impact of genetic variation in immunity-associated proteins on COVID-19 susceptibility and help guide drug-repurposing strategies.


Asunto(s)
COVID-19 , Mutación Missense , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , SARS-CoV-2/inmunología , COVID-19/genética , COVID-19/virología , COVID-19/inmunología , Reposicionamiento de Medicamentos , Proteínas Virales/genética , Proteínas Virales/metabolismo , Unión Proteica , Predisposición Genética a la Enfermedad , Susceptibilidad a Enfermedades , Tratamiento Farmacológico de COVID-19
18.
Opt Express ; 32(11): 18771-18789, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38859027

RESUMEN

Reconstructing high-quality images at a low measurement rate is a pivotal objective of Single-Pixel Imaging (SPI). Currently, deep learning methods achieve this by optimizing the loss between the target image and the original image, thereby constraining the potential of low measurement values. We employ conditional probability to ameliorate this, introducing the classifier-free guidance model (CFG) for enhanced reconstruction. We propose a self-supervised conditional masked classifier-free guidance (SCM-CFG) for single-pixel reconstruction. At a 10% measurement rate, SCM-CFG efficiently completed the training task, achieving an average peak signal-to-noise ratio (PSNR) of 26.17 dB on the MNIST dataset. This surpasses other methods of photon imaging and computational ghost imaging. It demonstrates remarkable generalization performance. Moreover, thanks to the outstanding design of the conditional mask in this paper, it can significantly enhance the accuracy of reconstructed images through overlay. SCM-CFG achieved a notable improvement of an average of 7.3 dB in overlay processing, in contrast to only a 1 dB improvement in computational ghost imaging. Subsequent physical experiments validated the effectiveness of SCM-CFG.

19.
ACS Appl Mater Interfaces ; 16(21): 27650-27656, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38747462

RESUMEN

Soft actuators possessing notable mechanical deformations, high sensitivity, and fast response speed play a crucial role in various applications, such as artificial muscles, soft robots, and intelligent devices. In this study, a smart humidity-driven actuator was successfully fabricated by utilizing MXene/cellulose nanofiber (CNF)/LiCl (MCL) through vacuum-assisted filtration with fast response speed and high sensitivity. Utilizing the excellent humidity responsiveness of MXene/CNF and the robust hygroscopicity of LiCl, the synergistic effect of these materials enhances the hygroscopic properties and response speed of the actuator. The MCL actuator demonstrates excellent actuation performance, fast deformation, and reliable cyclic stability. To illustrate the extensive potential of the soft actuator, a range of applications, from bionic devices to soft grippers and crawling actuators, are showcased. Remarkably, the crawling actuator demonstrates sustained crawling motion without necessitating a humidity switch, relying on the humidity gradient from water droplets, and exhibits spontaneous directional motions within a certain range, which makes it a promising prospect in the field of soft robotics.

20.
Artículo en Inglés | MEDLINE | ID: mdl-38782736

RESUMEN

AIM: This study aimed to establish a comprehensive set of recovery-oriented rehabilitation programs for individuals with schizophrenia, comparing the efficacy of video-based rehabilitation to traditional face-to-face interventions. The primary objective was to assess whether video-based rehabilitation could serve as a viable alternative for individuals with schizophrenia residing in remote areas. METHODS: A randomized controlled study was used to recruit 80 patients with schizophrenia in a stable post-hospitalization stage following discharge. Participants were categorized into three groups: 24 in the control group, 21 in the face-to-face group, and 35 in the remote group. Assessment parameters included psychiatric symptoms, social skills, family function and self-stigma. RESULTS: A total of 68 participants completed the program. The findings indicated significant differences (p < .05) between the control group and intervention group, particularly in the Positive and Negative Syndrome Scale (PANSS) and the Personal and Social Performance Scale (PSP). CONCLUSIONS: The rehabilitation program, tailored for patients in the early phase of the schizophrenia spectrum, demonstrates both effectiveness and feasibility in enhancing clinical symptoms and social functions. Notably, interventions conducted via video proved to be equally effective as those administered face-to-face.

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