Heat shock protein 90: biological functions, diseases, and therapeutic targets.

Heat shock protein 90 (Hsp90) is a predominant member among Heat shock proteins (HSPs), playing a central role in cellular protection and maintenance by aiding in the folding, stabilization, and modification of diverse protein substrates. It collaborates with various co-chaperones to manage ATPase-driven conformational changes in its dimer during client protein processing. Hsp90 is critical in cellular function, supporting the proper operation of numerous proteins, many of which are linked to diseases such as cancer, Alzheimer's, neurodegenerative conditions, and infectious diseases. Recognizing the significance of these client proteins across diverse diseases, there is a growing interest in targeting Hsp90 and its co-chaperones for potential therapeutic strategies. This review described biological background of HSPs and the structural characteristics of HSP90. Additionally, it discusses the regulatory role of heat shock factor-1 (HSF-1) in modulating HSP90 and sheds light on the dynamic chaperone cycle of HSP90. Furthermore, the review discusses the specific contributions of HSP90 in various disease contexts, especially in cancer. It also summarizes HSP90 inhibitors for cancer treatment, offering a thoughtful analysis of their strengths and limitations. These advancements in research expand our understanding of HSP90 and open up new avenues for considering HSP90 as a promising target for therapeutic intervention in a range of diseases.

An analysis of financial risk assessment of globally listed football clubs.

The global football market has grown in the past three decades, and football clubs' sustainable financial operations have gradually gained attention. This study aims to construct a financial risk assessment model applicable to the football industry, explore globally listed football clubs' overall financial operating characteristics, and analyse the leading causes of the club's financial crisis. We selected a sample of 24 currently listed football clubs worldwide and an exploratory factor analysis (EFA) model to construct the model of financial risk assessment for football clubs. The model identified and classified the financial risk components for listed football clubs, thus facilitating risk warning and prevention for modern professional clubs. This study found that football clubs are at higher financial risk overall, with the following general characteristics: (1) small amount of listed capital; (2) high asset-liability ratio; (3) low net profits and a large proportion of clubs make losses; and (4) weak asset liquidity. Finally, the study discussed the leading causes of the financial crises of football clubs in both external and internal dimensions, providing a reference for the self-sustainability of clubs and football authorities.

NRG1 promotes tumorigenesis and metastasis and afatinib treatment efficiency is enhanced by NRG1 inhibition in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a highly aggressive tumor with significant heterogeneity in incidence and outcomes. The role of Neuregulin 1 (NRG1) in ESCC and its contribution to aggressiveness remain unknown. This study aims to investigate the functions and molecular mechanisms of NRG1 in ESCC as well as the treatment strategy for ESCC with overexpression of NRG1. We firstly demonstrated the upregulation of NRG1 and a negative correlation trend between patients' overall survival (OS) and the expression level of NRG1 in esophageal cancer. And then we found NRG1 promoted cell proliferation, migration, inhibited apoptosis, and accelerated tumorigenesis and metastasis in ESCC using cell lines and xenograft models. Furthermore, we discovered that NRG1 activated the NF-κB/MMP9 signaling pathway, contributing to the metastatic phenotype in ESCC. Finally, we show that afatinib (FDA approved cancer growth blocker) could inhibit ESCC with overexpressed NRG1 and down-regulation of NRG1 along with afatinib treatment provides higher efficient strategy. This study uncovers the critical role and molecular mechanism of NRG1 in ESCC tumorigenesis and metastasis, suggesting its potential as a novel biomarker for ESCC treatment.

Transcriptome sequencing reveals fibrotic associated-genes involved in bovine mammary fibroblasts with Staphylococcus aureus.

Bovine mammary fibrosis represents a considerable health problem of cows, primarily indicated by lactation failure. Staphylococcus aureus (S. aureus) can cause mammary damage, this multifactorial disease necessitates to identify how and to what extent molecular pathogen defense mechanisms prevent bacterial infections in bovine mammary gland. In this study, we have aimed to determine the transcriptional responses in bovine mammary fibroblasts (BMFBs) induced by S. aureus using bioinformatics analysis to determine whether mRNA expression profile changes between BMFBs activation and quiescence. Established primary BMFBs obtained from healthy Holstein bovine were induced 106 CFU/mL heat-inactivated S. aureus and total RNA was isolated 6 h after treatment. The 574 DEGs were involved in gene ontology (GO) that were immune response, apoptotic process, extracellular region, receptor binding, endopeptidase activity and protein kinase activity et al. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, distinct pathway contained signaling molecules common to various inflammatory and fibrotic pathways were Pathways in cancer, Cytokine-cytokine receptor interaction, PI3K-Akt signaling pathway, TNF signaling pathway, MAPK signaling pathway and Toll-like receptor signaling pathway. The BMFBs was treated with heat-inactivated S. aureus (106 CFU/mL) and also with pharmacological inhibitors of ERK1/2, P38 MAPK and JNK. The MMP-2 activity were examined gelatin zymography, MMP-2, TIMP-1, -2 and PLAU/PAI-1 protein expression were examined in vitro by western blot. The MMP-2 activity was significantly inhibited by simultaneous inhibition of ERK1/2, P38 MAPK and JNK, and MMP-2, TIMP-1,-2 and PLAU/PAI-1 protein expression were significantly decreased by inhibiting ERK1/2, P38 MAPK or JNK. This suggested a crosstalk between the ERK1/2, P38 MAPK or JNK signaling pathways in regulating extracellular matrix metabolism in the BMFBs with S. aureus. Our study complement our initial study on S. aureus-induced responses by fibrosis-associated genes in BMFBs. This may lead to development of novel therapeutic targets to control bovine mammary fibrosis induced by S. aureus.

Investigation on the role of the dielectric loss in metamaterial absorber.

The authors report a metamaterial (MM) consisting of cut-wire structures which shows near-perfect absorption at microwave frequencies. Experimental results show slight lower performance than simulation. The analysis of the spectra and retrieved electromagnetic parameters demonstrate that the mismatch is attributed to the considerable influence of the dielectric loss on the strength of the electric and magnetic resonances, which largely determines the ability of the MM absorber. Such dependence on dielectric loss provides an important clue for the design of MM absorber aiming at specific applications where high efficiency energy collection in dielectric is needed.

Mixed plasmons coupling for expanding the bandwidth of near-perfect absorption at visible frequencies.

We theoretically investigate the electromagnetic response of mixed-size sub-wavelength square hole array (M-SHA) combined with thick metal layer (TML). Near-perfect absorption with bandwidth about 17 nm is firstly observed. Field distribution and dispersion relationship indicate that mixed surface plasmons (M-SPs) coupling is supported by M-SHA and TML. The absorption band is proved to be dominated by M-SPs coupling.

Realizing near-perfect absorption at visible frequencies.

Sub-wavelength hole array (SHA) combined with thick metal layer (TML) is shown to have simultaneous suppressed transmission and reflection, resulting near-perfect absorption. Unlike the simultaneous electric and magnetic resonances in electric ring resonator and cut wire [PRL, 100, 207402 (2008)], such behavior results from strong anti-symmetric surface plasmons coupling supported by SHA and TML. The polarization-free characteristic permits to construct an ideal absorber for some practical applications in turbid backgrounds.

Expanding the band of negative permeability of a composite structure with dual-band negative permeability.

We provide a design of a metallic composite structure, which simultaneously shows dual-band negative permeability (DNP) in two optical ranges. Numerical simulation demonstrates that different shifting of the two magnetic resonances can be observed. This structure property allows the realization of a wide range of negative permeability covering near-infrared (NIR) and visible ranges simultaneously. The alterability of the two neighboring negative permeability would provide a way to realize an effective pass-band of a meta-material with negative permeability at optical frequencies.

Analysis of optical SHG in photonic crystal consisting of centro-symmetric dielectric.

Optical second harmonic generation (OSHG) in a two-dimension photonic crystal consisting of centro-symmetric dielectric is investigated. The calculation model and analyzing method for OSHG are discussed. Based on Finite Difference-Time Domain algorithm, the electromagnetic field distribution in the structure and the intensity of second harmonic generation along the waveguide are analyzed. The results show that the acute spatial variation of electro-magnetic field results in the radiation of OSHG, and the intensity of OSHG is proportional to the square of the waveguide length. When the beam intensity of the pumping wave with a wavelength of 10.6 microm is 1.3MW/mm2, the power conversion efficiency is 0.268% for a silicon photonic crystal with a length of 40 microm.