GRP78 improves the therapeutic effect of mesenchymal stem cells on hemorrhagic shock-induced liver injury: Involvement of the NF-кB and HO-1/Nrf-2 pathways.

Mesenchymal stem cells (MSCs) are a popular cell source for repairing the liver. Improving the survival rate and colonization time of MSCs may significantly improve the therapeutic outcomes of MSCs. Studies showed that 78-kDa glucose-regulated protein (GRP78) expression improves cell viability and migration. This study aims to examine whether GRP78 overexpression improves the efficacy of rat bone marrow-derived MSCs (rBMSCs) in HS-induced liver damage. Bone marrow was isolated from the femurs and tibias of rats. rBMSCs were transfected with a GFP-labeled GRP78 expression vector. Flow cytometry, transwell invasion assay, scratch assay immunoblotting, TUNEL assay, MTT assay, and ELISA were carried out. The results showed that GRP78 overexpression enhanced the migration and invasion of rBMSCs. Moreover, GRP78-overexpressing rBMSCs relieved liver damage, repressed liver oxidative stress, and inhibited apoptosis. We found that overexpression of GRP78 in rBMSCs inhibited activation of the NLRP3 inflammasome, significantly decreased the levels of inflammatory factors, and decreased the expression of CD68. Notably, GRP78 overexpression activated the Nrf-2/HO-1 pathway and inhibited the NF-κB pathway. High expression of GRP78 efficiently enhanced the effect of rBMSC therapy. GRP78 may be a potential target to improve the therapeutic efficacy of BMSCs.

Impact of Hypoxia-Inducible Factor-1α on Host Immune Metabolism and Tissue Damage During Mycobacterium bovis Infection.

HIF-1α is a pivotal regulator of metabolic and inflammatory responses. This study investigated the role of HIF-1α in M. bovis infection and its effects on host immune metabolism and tissue damage. We evaluated the expression of immunometabolism markers and MMPs infected with M. bovis, and following HIF-1α inhibition in vitro. To understand the implications of HIF-1α inhibition on disease progression, mice at different infection stages were treated with the HIF-1α inhibitor, YC-1. Our results revealed an upregulation of the HIF-1α in macrophages post-M. bovis infection, facilitating enhanced M1 macrophage polarization. The blockade of HIF-1α moderated these responses but escalated MMP activity, hindering bacterial control. Consistent with our in vitro results, early-stage treatment of mice with YC-1 aggravated pathological alterations and tissue damage, while late-stage HIF-1α inhibition proved beneficial in managing the disease. Overall, our findings underscored the nuanced role of HIF-1α across varying phases of M. bovis infection.

Cu-OFF/ERI Zeolite: Intergrowth Structure Synergistically Boosting Selective Catalytic Reduction of NOx with NH3.

Cu-SSZ-13 has been commercialized for selective catalytic reduction with ammonia (NH3-SCR) to remove NOx from diesel exhaust. As its synthesis usually requires toxic and costly organic templates, the discovery of alternative Cu-based zeolite catalysts with organotemplate-free synthesis and comparable or even superior NH3-SCR activity to that of Cu-SSZ-13 is of great academic and industrial significance. Herein, we demonstrated that Cu-T with an intergrowth structure of offretite (OFF) and erionite (ERI) synthesized by an organotemplate-free method showed better catalytic performance than Cu-ERI and Cu-OFF as well as Cu-SSZ-13. Structure characterizations and density functional theory calculations indicated that the intergrowth structure promoted more isolated Cu2+ located at the 6MR of the intergrowth interface, resulting in a better hydrothermal stability of Cu-T than Cu-ERI and Cu-OFF. Strikingly, the low-temperature activity of Cu-T significantly increased after hydrothermal aging, while that of Cu-ERI and Cu-OFF substantially decreased. Based on in situ diffuse reflectance infrared Fourier transform spectra analysis and density functional theory calculations, the reason can be attributed to the fact that NH4NO3 formed on the CuxOy species within ERI polymorph of Cu-T underwent a fast SCR reaction pathway with the assistance of Brønsted acid sites at the intergrowth interfaces under standard SCR reaction conditions. Significantly, Cu-T exhibited a wider temperature window at a catalytic activity of over 90% than Cu-SSZ-13 (175-550 vs 175-500 °C for fresh and 225-500 vs 250-400 °C for hydrothermal treatment). This work provides a new direction for the design of high-performance NH3-SCR catalysts in terms of the interplay of the intergrowth structure of zeolites.

NSUN2/YBX1 promotes the progression of breast cancer by enhancing HGH1 mRNA stability through m5C methylation.

BACKGROUND: RNA m5C methylation has been extensively implicated in the occurrence and development of tumors. As the main methyltransferase, NSUN2 plays a crucial regulatory role across diverse tumor types. However, the precise impact of NSUN2-mediated m5C modification on breast cancer (BC) remains unclear. Our study aims to elucidate the molecular mechanism underlying how NSUN2 regulates the target gene HGH1 (also known as FAM203) through m5C modification, thereby promoting BC progression. Additionally, this study targets at preliminarily clarifying the biological roles of NSUN2 and HGH1 in BC. METHODS: Tumor and adjacent tissues from 5 BC patients were collected, and the m5C modification target HGH1 in BC was screened through RNA sequencing (RNA-seq) and single-base resolution m5C methylation sequencing (RNA-BisSeq). Methylation RNA immunoprecipitation-qPCR (MeRIP-qPCR) and RNA-binding protein immunoprecipitation-qPCR (RIP-qPCR) confirmed that the methylation molecules NSUN2 and YBX1 specifically recognized and bound to HGH1 through m5C modification. In addition, proteomics, co-immunoprecipitation (co-IP), and Ribosome sequencing (Ribo-Seq) were used to explore the biological role of HGH1 in BC. RESULTS: As the main m5C methylation molecule, NSUN2 is abnormally overexpressed in BC and increases the overall level of RNA m5C. Knocking down NSUN2 can inhibit BC progression in vitro or in vivo. Combined RNA-seq and RNA-BisSeq analysis identified HGH1 as a potential target of abnormal m5C modifications. We clarified the mechanism by which NSUN2 regulates HGH1 expression through m5C modification, a process that involves interactions with the YBX1 protein, which collectively impacts mRNA stability and protein synthesis. Furthermore, this study is the first to reveal the binding interaction between HGH1 and the translation elongation factor EEF2, providing a comprehensive understanding of its ability to regulate transcript translation efficiency and protein synthesis in BC cells. CONCLUSIONS: This study preliminarily clarifies the regulatory role of the NSUN2-YBX1-m5C-HGH1 axis from post-transcriptional modification to protein translation, revealing the key role of abnormal RNA m5C modification in BC and suggesting that HGH1 may be a new epigenetic biomarker and potential therapeutic target for BC.

Unsupervised OCT image despeckling with ground-truth- and repeated-scanning-free features.

Optical coherence tomography (OCT) can resolve biological three-dimensional tissue structures, but it is inevitably plagued by speckle noise that degrades image quality and obscures biological structure. Recently unsupervised deep learning methods are becoming more popular in OCT despeckling but they still have to use unpaired noisy-clean images or paired noisy-noisy images. To address the above problem, we propose what we believe to be a novel unsupervised deep learning method for OCT despeckling, termed Double-free Net, which eliminates the need for ground truth data and repeated scanning by sub-sampling noisy images and synthesizing noisier images. In comparison to existing unsupervised methods, Double-free Net obtains superior denoising performance when trained on datasets comprising retinal and human tissue images without clean images. The efficacy of Double-free Net in denoising holds significant promise for diagnostic applications in retinal pathologies and enhances the accuracy of retinal layer segmentation. Results demonstrate that Double-free Net outperforms state-of-the-art methods and exhibits strong convenience and adaptability across different OCT images.

Differential inhibition of sildenafil and macitentan on saxagliptin metabolism.

The development of diabetes mellitus (DM) is generally accompanied by erectile dysfunction (ED) and pulmonary arterial hypertension (PAH), which increases the use of combination drug therapy and the risk of drug-drug interactions. Saxagliptin for the treatment of DM, sildenafil for the treatment of ED and PAH, and macitentan for the treatment of PAH are all substrates of CYP3A4, which indicates their potential involvement in drug-drug interactions. Therefore, we investigated potential pharmacokinetic interactions between saxagliptin and sildenafil/macitentan. We investigated this speculation both in vitro and in vivo, and explored the underlying mechanism using in vitro hepatic metabolic models and molecular docking assays. The results showed that sildenafil substantially inhibited the metabolism of saxagliptin by occupying the catalytic site of CYP3A4 in a competitive manner, leading to the alterations in the pharmacokinetic properties of saxagliptin in terms of increased maximum plasma concentration (Cmax), area under the plasma concentration-time curve from time 0 to 24 h (AUC(0-t)), area under the plasma concentration-time curve from time 0 extrapolated to infinite time (AUC(0-∞)), decreased clearance rate (CLz/F), and prolonged terminal half-life (t1/2). In contrast, a slight inhibition was observed in saxagliptin metabolism when concomitantly used with macitentan, as no pharmacokinetic parameters were altered, except for CLz/F. Thus, dosage adjustment of saxagliptin may be required in combination with sildenafil to achieve safe therapeutic plasma concentrations and reduce the risk of potential toxicity, but it is not necessary for co-administration with macitentan.

Effect of Annealing on Visible-Bubble Formation and Stability Profiles of Freeze-Dried High Concentration Omalizumab Formulations.

In the clinical application of freeze-dried highly concentrated omalizumab formulations, extensive visible bubbles (VBs) can be generated and remain for a long period of time in the reconstitution process, which greatly reduces the clinical use efficiency. It is necessary to understand the forming and breaking mechanism of VBs in the reconstitution process, which is a key factor for efficient and safe administration of biopharmaceutical injection. The effects of different thermal treatments on the volume of VBs and stability of omalizumab, mAb-1, and mAb-2 were investigated. The internal microvoids of the cake were characterized by scanning electron microscopy and mercury intrusion porosimetry. Electron paramagnetic resonance was applied to obtain the molecular mobility of the protein during annealing. A large number of VBs were generated in the reconstitution process of unannealed omalizumab and remained for a long period of time. When annealing steps were added, the volume of VBs was dramatically reduced. When annealed at an aggressive temperature (i.e., -6 °C), although the volume of VBs decreased, the aggregation and acidic species increased significantly. Thus, our observations highlight the importance of setting an additional annealing step with a suitable temperature, which contributes to reducing the VBs while maintaining the stability of the high concentration freeze-dried protein formulation.

Supercapacitor Performance of Sulfonyldibenzene Derivative-Functionalized Graphene Aerogel.

3D aerogels incorporating functionalized reduced graphene oxide (SUL/rGO) were prepared as a hydrothermal method utilizing graphene oxide (GO) and a sulfonyldibenzene derivative (SUL) as raw materials. The aromatic compound SUL, which contains hydroxyl and sulfonyl groups, was bonded to reduced graphene oxide (rGO) through π-π connections. The obtained composite material exhibited porosity within its structure with improved hydrophilicity, along with excellent electrochemical characteristics. This improvement was ascribed to the specific rGO structure, as well as the pseudocapacitance inherent in SUL, both of which synergistically contribute to improvement in the characteristics of the prepared electrode materials. Also, an analysis was performed employing density functional theory from which the density of states and adsorption energy of SUL on the surface of rGO were computed to further investigate the charge storage process within the prepared composite. The prepared SUL/rGO-2 electrode exhibited the highest specific capacitance value of 388 F/g at a current density equal to 1 A/g. The constructed symmetrical supercapacitor, SUL/rGO-2//SUL/rGO-2, attained an energy density value of 14.55 Wh/kg at a power density equal to 350 W/kg with an exceptional galvanostatic charge-discharge (GCD) cyclic stability equal to 91% following 10 000 cycles. Therefore, this review presents a novel functionalized graphene-based material incorporating hydroxyl and sulfonyl groups, which holds promise in future energy storage applications.

The Effects of Excipients on Freeze-dried Monoclonal Antibody Formulation Degradation and Sub-Visible Particle Formation during Shaking.

PURPOSES: We previously reported an unexpected phenomenon that shaking stress could cause more protein degradation in freeze-dried monoclonal antibody (mAb) formulations than liquid ones (J Pharm Sci, 2022, 2134). The main purposes of the present study were to investigate the effects of shaking stress on protein degradation and sub-visible particle (SbVP) formation in freeze-dried mAb formulations, and to analyze the factors influencing protein degradation during production and transportation. METHODS: The aggregation behavior of mAb-X formulations during production and transportation was simulated by shaking at a rate of 300 rpm at 25°C for 24 h. The contents of particles and monomers were analyzed by micro-flow imaging, dynamic light scattering, size exclusion chromatography, and ultraviolet - visible (UV-Vis) spectroscopy to compare the protective effects of excipients on the aggregation of mAb-X. RESULTS: Shaking stress could cause protein degradation in freeze-dried mAb-X formulations, while surfactant, appropriate pH, polyol mannitol, and high protein concentration could impact SbVP generation. Water content had little effect on freeze-dried protein degradation during shaking, as far as the water content was controlled in the acceptable range as recommended by mainstream pharmacopoeias (i.e., less than 3%). CONCLUSIONS: Shaking stress can reduce the physical stability of freeze-dried mAb formulations, and the addition of surfactants, polyol mannitol, and a high protein concentration have protective effects against the degradation of model mAb formulations induced by shaking stress. The experimental results provide new insight for the development of freeze-dried mAb formulations.

Factors associated with out-of-school physical activity among Chinese children and adolescents: A stratified cross-sectional study.

OBJECTIVE: This observational study examined the factors associated with the physical activity (PA) of children and adolescents outside of school within the framework of Problem Behavior Theory (PBT). METHODS: This cross-sectional study obtained data from 6528 children and adolescents aged 6-16 years recruited from ten schools in Shanghai, China. The questionnaire measured out-of-school PA and PBT-based correlates. A series of multiple linear regressions were used to explore the factors influencing children and adolescents' out-of-school PA separately. Structural equation modeling (SEM) was used to explore the association between the three systems of PBT and out-of-school PA. RESULTS: Higher intrinsic motivation is positively associated with increased PA for children (b = 1.038, 95%CI: 0.897-1.180) and adolescents (b = 1.207, 95%CI: 0.890-1.524). Greater frequency of parental involvement in PA correlates with elevated PA for both children (b = 2.859, 95%CI: 2.147-3.572) and adolescents (b = 2.147, 95%CI: 0.311-3.983). In children, increased use of community exercise areas or facilities (b = 1.705, 95%CI: 0.234-3.176) and higher recreational screen time (b = 9.732, 95%CI: 5.614-13.850) are associated with higher PA. The SEM showed that factors of the personality system had a significant direct effect on out-of-school PA among children and adolescents, and factors of the behavior system also had a significant effect on children. CONCLUSIONS: Our findings suggest that the personality system, particularly intrinsic motivation, is important in promoting out-of-school PA in children and adolescents. For children, modifiable health behaviors in the behavior system can similarly influence PA.

Construction of programmed time-released multifunctional hydrogel with antibacterial and anti-inflammatory properties for impaired wound healing.

The successful reprogramming of impaired wound healing presents ongoing challenges due to the impaired tissue microenvironment caused by severe bacterial infection, excessive oxidative stress, as well as the inappropriate dosage timing during different stages of the healing process. Herein, a dual-layer hydrogel with sodium alginate (SA)-loaded zinc oxide (ZnO) nanoparticles and poly(N-isopropylacrylamide) (PNIPAM)-loaded Cu5.4O ultrasmall nanozymes (named programmed time-released multifunctional hydrogel, PTMH) was designed to dynamically regulate the wound inflammatory microenvironment based on different phases of wound repairing. PTMH combated bacteria at the early phase of infection by generating reactive oxygen species through ZnO under visible-light irradiation with gradual degradation of the lower layer. Subsequently, when the upper layer was in direct contact with the wound tissue, Cu5.4O ultrasmall nanozymes were released to scavenge excessive reactive oxygen species. This neutralized a range of inflammatory factors and facilitated the transition from the inflammatory phase to the proliferative phase. Furthermore, the utilization of Cu5.4O ultrasmall nanozymes enhanced angiogenesis, thereby facilitating the delivery of oxygen and nutrients to the impaired tissue. Our experimental findings indicate that PTMHs promote the healing process of diabetic wounds with bacterial infection in mice, exhibiting notable antibacterial and anti-inflammatory properties over a specific period of time.

The influence factors on pit and fissure sealing behavior of 12-year-old children: a cross-sectional study in Zhejiang, China.

BACKGROUND: In the 21st century, dental caries remains a global burden, particularly severely affecting the growth and quality of life of 12-year-old children. Fortunately, pit and fissure sealing (PFS) procedures can effectively prevent molars from caries. Hence, this study focused on the relationship between PFS and oral epidemiological factors in 12-year-old children. METHODS: A cross-sectional survey was conducted in 12-year-old children from 11 cities in Zhejiang Province. Their dental conditions were collected through questionnaires, as well as basic information such as relevant family information, oral health knowledge and behavior. Then, logistic regression analysis was used to identify the influencing factors associated with PFS. RESULTS: A total of 1204 children were included, with 252 in the PFS group and 952 in the non-PFS group. There were significant differences between the two groups in terms of decayed, missing and filled teeth (DMFT) score, first permanent molar DMFT score, residential area, educational level of parents, tooth-brushing frequency, use of dental floss, oral examination in a medical institution, having taken courses on oral health care, as well as having knowledge that tooth brushing could effectively prevent gingival inflammation, PFS could protect teeth, and oral disease may affect general health. According to further logistic regression analysis, the independent factors influencing PFS included use of dental floss [odds ratios (OR) = 1.672, 95% confidence intervals (CI) = 1.235-2.263, P = 0.001], having taken courses on oral health care (OR = 0.713, 95% CI = 0.515-0.988, P = 0.042), having knowledge that tooth brushing is effective in preventing gingival inflammation (OR = 0.627, 95% CI = 0.389-0.987, P = 0.044) and having knowledge that PFS can protect teeth (OR = 0.589, 95% CI = 0.438-0.791, P < 0.001). CONCLUSION: PFS can reduce the mean DMFT score of 12-year-old children. Independent influencing factors of PFS consist of use of dental floss, having taken courses on oral health care, oral health behavior and knowledge level.

How race and socioeconomic status moderate the association between moderate-to-vigorous physical activity and depressive symptoms: a cross-sectional study with compositional data.

OBJECTIVES: This study explored how race and socioeconomic status (SES) moderated the association between moderate-to-vigorous physical activity (MVPA) and depressive symptoms with compositional data. METHODS: Participants were 2803 US adults from the 2005-2006 cycle of the National Health and Nutrition Examination Survey. Accelerometers were used to measure MVPA, light-intensity physical activity (LPA) and sedentary behaviours (SB). Participants self-reported sleep duration and depressive symptoms. SES was derived by latent class analysis using household income level, education attainment and occupation. The association between the relative time of MVPA and depressive symptoms and the moderating effects of race and SES were investigated through compositional data analysis. Isotemporal substitution analysis was employed to estimate the association of time reallocation from other movement behaviours to MVPA with depressive symptoms. RESULTS: Increased time spent in MVPA relative to time spent in LPA, SB and sleep was inversely associated with depressive symptoms (OR (95% CI)=0.679 (0.538-0.855)). The relative time of MVPA significantly interacted with race and SES for depressive symptoms (P for interaction <0.05). Reallocating 10-30 min from sleep, SB or LPA to MVPA was associated with lower odds of depressive symptoms solely among non-Hispanic white individuals and those with higher SES. CONCLUSION: This study used compositional data to reveal a reverse association between MVPA and depressive symptoms among white individuals and those with higher SES. Our results provide evidence of how race and SES moderate the relationship between MVPA and depressive symptoms. Future research is needed to further explore these racial and socioeconomic differences.

Analysis of the correlation mechanism between geometric parameters and the thermal environment of Xi'an's summer outdoor commercial pedestrian streets.

Intensive urban development has resulted in the degradation of the urban thermal environment in most regions. There is a growing consensus on the need to enhance urban thermal comfort through well-designed forms, especially in open spaces like urban canyons. To address this, our study focuses on Xi'an's commercial pedestrian streets, employing K-means clustering analysis to create 32 representative models based on actual scenes, capturing their textural characteristics. Simultaneously, 11 geometric indicators (2D/3D) were chosen to quantify the canyon's geometric form. We assessed the spatial and temporal distribution differences in the thermal environment across these models using Envi-met simulation. Finally, Spearman correlation analysis was employed to examine the correlation and significance of the two sets of indicators, culminating in formulating an ideal model. The findings reveal that (1) wind conditions are predominantly influenced by the canyon's geometric form, followed by solar radiation and temperature, with the lowest relative humidity change amplitude among the assessed thermal parameters. (2) Among the 11 geometric form indicators, 3D indicators correlate more significantly with thermal environment parameters than 2D indicators. Specifically, street orientation significantly impacts the thermal environment, Build-To-Line Rat holds greater significance than interface density, and both building shape coefficient and block surface ratio are significantly correlated with air temperature and wind speed, with a weaker correlation to solar radiation. (3) In the Xi'an region, courtyards oriented north-south demonstrate a more favorable trend in the thermal environment.

Oxygen Vacancies Boosted Hydronium Intercalation: A Paradigm Shift in Aluminum-Based Batteries.

In aqueous aluminum-ion batteries (AAIBs), the insertion/extraction chemistry of Al3+ often leads to poor kinetics, whereas the rapid diffusion kinetics of hydronium ions (H3O+) may offer the solution. However, the presence of considerable Al3+ in the electrolyte hinders the insertion reaction of H3O+. Herein, we report how oxygen-deficient α-MoO3 nanosheets unlock selective H3O+ insertion in a mild aluminum-ion electrolyte. The abundant oxygen defects impede the insertion of Al3+ due to excessively strong adsorption, while allowing H3O+ to be inserted/diffused through the Grotthuss proton conduction mechanism. This research advances our understanding of the mechanism behind selective H3O+ insertion in mild electrolytes.

Generation of Protease Inhibitory Antibodies by Functional In Vivo Selection.

Targeting dysregulated protease expression and/or abnormal substrate proteolysis, highly selective inhibition of pathogenic proteases by monoclonal antibodies (mAbs) presents an attractive therapeutic approach for the treatment of diseases including cancer. Herein, we report a functional selection method for protease inhibitory mAbs by periplasmic co-expression of three recombinant proteins-a protease of interest, an antibody Fab library, and a modified ß-lactamase TEM-1. We validate this approach by isolation of highly selective and potent mAbs inhibiting human matrix metalloproteinase 9 (MMP9).

Large T antigen mediated target gene replication improves site-specific recombination efficiency.

With advantages of high-fidelity, monoclonality and large cargo capacity, site-specific recombination (SSR) holds great promises for precise genomic modifications. However, broad applications of SSR have been hurdled by low integration efficiency, and the amount of donor DNA available in nucleus for SSR presents as a limiting factor. Inspired by the DNA replication mechanisms observed in double-stranded DNA virus SV40, we hypothesized that expression of SV40 large T antigen (TAg) can increase the copy number of the donor plasmid bearing an SV40 origin, and in consequence promote recombination events. This hypothesis was tested with dual recombinase-mediated cassette exchange (RMCE) in suspension 293F cells. Results showed that TAg co-transfection significantly enhanced SSR in polyclonal cells. In the monoclonal cell line carrying a single landing pad at an identified genomic locus, 12% RMCE efficiency was achieved, and such improvement was indeed correlated with donor plasmid amplification. The developed TAg facilitated RMCE (T-RMCE) was exploited for the construction of large libraries of >107 diversity, from which GFP variants with enhanced fluorescence were isolated. We expect the underlying principle of target gene amplification can be applicable to other SSR processes and gene editing approaches in general for directed evolution and large-scale genomic screening in mammalian cells.

Comprehensive analysis of PSME3: from pan-cancer analysis to experimental validation.

PSME3 plays a significant role in tumor progression. However, the prognostic value of PSME3 in pan-cancer and its involvement in tumor immunity remain unclear. We conducted a comprehensive study utilizing extensive RNA sequencing data from the TCGA (The Cancer Genome Atlas) and GTEx (Genotype-Tissue Expression) databases. Our research revealed abnormal expression levels of PSME3 in various cancer types and unveiled a correlation between high PSME3 expression and adverse clinical outcomes, especially in cancers like liver cancer (LIHC) and lung adenocarcinoma (LUAD). Functional enrichment analysis highlighted multiple biological functions of PSME3, including its involvement in protein degradation, immune responses, and stem cell regulation. Moreover, PSME3 showed associations with immune infiltration and immune cells in the tumor microenvironment, indicating its potential role in shaping the cancer immune landscape. The study also unveiled connections between PSME3 and immune checkpoint expression, with experimental validation demonstrating that PSME3 positively regulates CD276. This suggests that PSME3 could be a potential therapeutic target in immunotherapy. Additionally, we predicted sensitive drugs targeting PSME3. Finally, we confirmed in both single-factor Cox and multiple-factor Cox regression analyses that PSME3 is an independent prognostic factor. We also conducted preliminary validations of the impact of PSME3 on cell proliferation and wound healing in liver cancer. In summary, our study reveals the multifaceted role of PSME3 in cancer biology, immune regulation, and clinical outcomes, providing crucial insights for personalized cancer treatment strategies and the development of immunotherapy.

Enhancing Ultraviolet Stability and Performance of Wide Bandgap Perovskite Solar Cells Through Ultraviolet Light-Absorbing Passivator.

Ultraviolet light (UV) has caused tremendous damage to perovskite solar cells (PSCs), degrading the perovskite and shortening their lifetime. Defects act as non-radiative recombination sites, accelerate the degradation process, reduce the efficiency of the device and weaken the stability of solar cell. In this work, to realize efficient and stable p-i-n wide bandgap solar cells under UV, a synergetic strategy utilizing UV light-absorbing passivator, (Trifluoroacetyl) benzotriazole (TFABI), enhance UV photostability and regulate the defect passivation is proposed. By using TFABI, the degradation of the perovskite absorption layer under UV light is suppressed, spectral response is enhanced and the Pb vacancy defects are passivated. As a result, the target device achieves an efficiency of 21.54%, exhibiting excellent long-term stability under 365 nm UV irradiation. After 60 h of irradiation, it retains 85% of its initial value (60 mW cm-2 , RH 25-30%, 25 °C).

Identification of novel hub genes for Alzheimer's disease associated with the hippocampus using WGCNA and differential gene analysis.

Background: Alzheimer's disease (AD) is a common, refractory, progressive neurodegenerative disorder in which cognitive and memory deficits are highly correlated with abnormalities in hippocampal brain regions. There is still a lack of hippocampus-related markers for AD diagnosis and prevention. Methods: Differently expressed genes were identified in the gene expression profile GSE293789 in the hippocampal brain region. Enrichment analyses GO, KEGG, and GSEA were used to identify biological pathways involved in the DEGs and AD-related group. WGCNA was used to identify the gene modules that are highly associated with AD in the samples. The intersecting genes of the genes in DEGs and modules were extracted and the top ten ranked hub genes were identified. Finally GES48350 was used as a validation cohort to predict the diagnostic efficacy of hub genes. Results: From GSE293789, 225 DEGs were identified, which were mainly associated with calcium response, glutamatergic synapses, and calcium-dependent phospholipid-binding response. WGCNA analysis yielded dark green and bright yellow modular genes as the most relevant to AD. From these two modules, 176 genes were extracted, which were taken to be intersected with DEGs, yielding 51 intersecting genes. Then 10 hub genes were identified in them: HSPA1B, HSPB1, HSPA1A, DNAJB1, HSPB8, ANXA2, ANXA1, SOX9, YAP1, and AHNAK. Validation of these genes was found to have excellent diagnostic performance. Conclusion: Ten AD-related hub genes in the hippocampus were identified, contributing to further understanding of AD development in the hippocampus and development of targets for therapeutic prevention.