SMYD2 induced PGC1α methylation promotes stemness maintenance of glioblastoma stem cells.

BACKGROUND: The high fatality rate of glioblastoma (GBM) is attributed to glioblastoma stem cells (GSCs), which exhibit heterogeneity and therapeutic resistance. Metabolic plasticity of mitochondria is the hallmark of GSCs. Targeting mitochondrial biogenesis of GSCs is crucial for improving clinical prognosis in GBM patients. METHODS: SMYD2-induced PGC1α methylation and followed nuclear export is confirmed by co-immunoprecipitation, cellular fractionation, and immunofluorescence. The effects of SMYD2/PGC1α/CRM1 axis on GSCs mitochondrial biogenesis is validated by OCR, ECAR and intracranial glioma model. RESULTS: PGC1α methylation causes disabled mitochondrial function to maintain the stemness, thereby enhancing radio-resistance of GSCs. SMYD2 drives PGC1α K224 methylation (K224me), which is essential for promoting the stem-like characteristics of GSCs. PGC1α K224me is preferred binding with CRM1, accelerating PGC1α nuclear export and subsequent dysfunction. Targeting PGC1α methylation exhibits significant radiotherapeutic efficacy and prolongs patient survival. CONCLUSIONS: These findings unveil a novel regulatory pathway involving mitochondria that governs stemness in GSCs, thereby emphasizing promising therapeutic strategies targeting PGC1α and mitochondria for the treatment of GBM.

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.

Potent human monoclonal antibodies targeting Epstein-Barr virus gp42 reveal vulnerable sites for virus infection.

Epstein-Barr virus (EBV) is linked to various malignancies and autoimmune diseases, posing a significant global health challenge due to the lack of specific treatments or vaccines. Despite its crucial role in EBV infection in B cells, the mechanisms of the glycoprotein gp42 remain elusive. In this study, we construct an antibody phage library from 100 EBV-positive individuals, leading to the identification of two human monoclonal antibodies, 2B7 and 2C1. These antibodies effectively neutralize EBV infection in vitro and in vivo while preserving gp42's interaction with the human leukocyte antigen class II (HLA-II) receptor. Structural analysis unveils their distinct binding epitopes on gp42, different from the HLA-II binding site. Furthermore, both 2B7 and 2C1 demonstrate potent neutralization of EBV infection in HLA-II-positive epithelial cells, expanding our understanding of gp42's role. Overall, this study introduces two human anti-gp42 antibodies with potential implications for developing EBV vaccines targeting gp42 epitopes, addressing a critical gap in EBV research.

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.

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.

Recent Advances in Carbon-Based Single-Atom Catalysts for Electrochemical Oxygen Reduction to Hydrogen Peroxide in Acidic Media.

Electrochemical oxygen reduction reaction (ORR) via the 2e- pathway in an acidic media shows great techno-economic potential for the production of hydrogen peroxide. Currently, carbon-based single-atom catalysts (C-SACs) have attracted extensive attention due to their tunable electronic structures, low cost, and sufficient stability in acidic media. This review summarizes recent advances in metal centers and their coordination environment in C-SACs for 2e--ORR. Firstly, the reaction mechanism of 2e--ORR on the active sites of C-SACs is systematically presented. Secondly, the structural regulation strategies for the active sites of 2e--ORR are further summarized, including the metal active center, its species and configurations of nitrogen coordination or heteroatom coordination, and their near functional groups or substitute groups, which would provide available and proper ideas for developing superior acidic 2e--ORR electrocatalysts of C-SACs. Finally, we propose the current challenges and future opportunities regarding the acidic 2e--ORR pathway on C-SACs, which will eventually accelerate the development of the distributed H2O2 electrosynthesis process.

Moderating effect of education on glymphatic function and cognitive performance in mild cognitive impairment.

Objective: This research aims to investigate putative mechanisms between glymphatic activity and cognition in mild cognitive impairment (MCI) and analyzes whether the relationship between cognitive reserve (CR) and cognition was mediated by glymphatic activity. Methods: 54 MCI patients and 31 NCs were enrolled to evaluate the bilateral diffusivity along the perivascular spaces and to acquire an index for diffusivity along the perivascular space (ALPS-index) on diffusion tensor imaging (DTI). The year of education was used as a proxy for CR. The ALPS-index was compared between two groups and correlation analyses among the ALPS-index, cognitive function, and CR were conducted. Mediation analyses were applied to investigate the correlations among CR, glymphatic activity and cognition. Results: MCI group had a significantly lower right ALPS-index and whole brain ALPS-index, but higher bilateral diffusivity along the y-axis in projection fiber area (Dyproj) than NCs. In MCI group, the left Dyproj was negatively related to cognitive test scores and CR, the whole brain ALPS-index was positively correlated with cognitive test scores and CR. Mediation analysis demonstrated that glymphatic activity partially mediated the correlations between CR and cognitive function. Conclusion: MCI exhibited decreased glymphatic activity compared to NCs. CR has a protective effect against cognitive decline in MCI, and this effect may be partially mediated by changes in glymphatic activity.

Multicomponent Pathogen-Mimicking Nanoparticles Induce Intestinal Immune Responses against Paratuberculosis.

Given the worldwide problem posed by enteric pathogens, the discovery of safe and efficient intestinal adjuvants combined with novel antigen delivery techniques is essential to the design of mucosal vaccines. In this work, we designed poly (lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) to codeliver all-trans retinoic acid (atRA), novel antigens, and CpG. To address the insolubility of the intestinal adjuvant atRA, we utilized PLGA to encapsulate atRA and form a "nanocapsid" with polydopamine. By leveraging polydopamine, we adsorbed the water-soluble antigens and the TLR9 agonist CpG onto the NPs' surface, resulting in the pathogen-mimicking PLPCa NPs. In this study, the novel fusion protein (HBf), consisting of the Mycobacterium avium subspecies paratuberculosis antigens HBHA, Ag85B, and Bfra, was coloaded onto the NPs. In vitro, PLPCa NPs were shown to promote the activation and maturation of bone marrow-derived dendritic cells. Additionally, we found that PLPCa NPs created an immune-rich microenvironment at the injection site following intramuscular administration. From the results, the PLPCa NPs induced strong IgA levels in the gut in addition to enhancing powerful systemic immune responses. Consequently, significant declines in the bacterial burden and inflammatory score were noted in PLPCa NPs-treated mice. In summary, PLPCa can serve as a novel and safe vaccine delivery platform against gut pathogens, such as paratuberculosis, capable of activating both systemic and intestinal immunity.

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.

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 hydrated hydrogen 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.

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.

Significant influence of urban human activities and marine input on rainwater chemistry in a coastal large city, China.

The coastal urban region is generally considered an atmospheric receptor for terrestrial and marine input materials, and rainfall chemistry can trace the wet scavenging process of these materials. Fast urbanization in China's east coastal areas has greatly altered the rainwater chemistry. However, the chemical variations, determinants, and sources of rainfall are unclear. Therefore, the typical coastal city of Fuzhou was selected for 1-year rainwater sampling and inorganic ions were detected to explore above problems. The findings depicted that rainwater ions in Fuzhou were slightly different from those in other coastal cities. Although NO3-, SO42-, Ca2+ and NH4+ dominated the rainwater ions, the marine input Cl- (22 %) and Na+ (11 %) also contributed a considerable percentage to the rainwater ions. Large differences in ion concentrations (2∼28 times) were found in monthly scale due to the rainfall amount. Both natural and anthropogenic determinants influenced the rainwater ions in coastal cities, such as SO2 emission, air SO2 and PM10 content on rainwater SO42-, NO3-, and Ca2+, and soot & dust emission on rainwater SO42-, NO3-, indicating the vital contribution of human activities. Stoichiometry and positive matrix factorization-based sources identification indicated that atmospheric dust/particles were the primary contributor of Ca2+ (83.3 %) and F- (83.7 %), and considerable contributor of SO42- (39.5 %), NO3- (38.3 %) and K+ (41.5 %). Anthropogenic origins, such as urban waste volatilization and fuel combustion emission, contributed 95 % of NH4+, 54.5 % of NO3- and 41.9 % of SO42-, and the traffic sources contribution was relatively higher than fixed emission sources. The marine input represented the vital source of Cl- (77.7 %), Na+ (84.9 %), and Mg2+ (55.3 %). This work highlights the significant influence of urban human activities and marine input on rainwater chemicals and provides new insight into the material cycle between the atmosphere and earth-surface in coastal city.

Whole-tumor histogram analysis of synthetic magnetic resonance imaging predicts isocitrate dehydrogenase mutation status in gliomas.

Background: An accurate assessment of isocitrate dehydrogenase (IDH) status in patients with glioma is crucial for treatment planning and is a key factor in predicting patient outcomes. In this study, we investigated the potential value of whole-tumor histogram metrics derived from synthetic magnetic resonance imaging (MRI) in distinguishing IDH mutation status between astrocytoma and glioblastoma. Methods: In this prospective study, 80 glioma patients were enrolled from September 2019 to June 2022. All patients underwent pre- and post-contrast synthetic MRI scan protocol. Immunohistochemistry (IHC) staining or gene sequencing were used to assess IDH mutation status in tumor tissue samples. Whole-tumor histogram metrics, including T1, T2, proton density (PD), etc., were extracted from the quantitative maps, while radiological features were assessed by synthetic contrast-weighted maps. Basic clinical features of the patients were also evaluated. Differences in clinical, radiological, and histogram metrics between IDH-mutant astrocytoma and IDH-wildtype glioblastoma were analyzed using univariate analyses. Variables with statistical significance in univariate analysis were included in multivariate logistic regression analysis to develop the combined model. Receiver operating characteristic (ROC) and area under the curve (AUC) were used to assess the diagnostic performance of metrics and models. Results: The histopathologic analysis revealed that of the 80 cases, 41 were classified as IDH-mutant astrocytoma and 39 as IDH-wildtype glioblastoma. Compared to IDH-wildtype glioblastoma, IDH-mutant astrocytoma showed significantly lower T1 [10th percentile (10th), mean, and median] and post-contrast PD (10th, 90th percentile, mean, median, and maximum) values as well as higher post-contrast T1 (cT1) (10th, mean, median, and minimum) values (all P<0.05). The combined model (T1-10th + cT1-10th + age) was developed by integrating the independent influencing factors of IDH-mutant astrocytoma using the multivariate logistic regression. The diagnostic performance of this model [AUC =0.872 (0.778-0.936), sensitivity =75.61%, and specificity =89.74%] was superior to the clinicoradiological model, which was constructed using age and enhancement degree (AUC =0.822 (0.870-0.898), P=0.035). Conclusions: The combined model constructed using histogram metrics derived from synthetic MRI could be a valuable preoperative tool to distinguish IDH mutation status between astrocytoma and glioblastoma, and subsequently, could assist in the decision-making process of pretreatment.

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.

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.

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.

Reactivating PTEN to impair glioma stem cells by inhibiting cytosolic iron-sulfur assembly.

Glioblastoma, the most lethal primary brain tumor, harbors glioma stem cells (GSCs) that not only initiate and maintain malignant phenotypes but also enhance therapeutic resistance. Although frequently mutated in glioblastomas, the function and regulation of PTEN in PTEN-intact GSCs are unknown. Here, we found that PTEN directly interacted with MMS19 and competitively disrupted MMS19-based cytosolic iron-sulfur (Fe-S) cluster assembly (CIA) machinery in differentiated glioma cells. PTEN was specifically succinated at cysteine (C) 211 in GSCs compared with matched differentiated glioma cells. Isotope tracing coupled with mass spectrometry analysis confirmed that fumarate, generated by adenylosuccinate lyase (ADSL) in the de novo purine synthesis pathway that is highly activated in GSCs, promoted PTEN C211 succination. This modification abrogated the interaction between PTEN and MMS19, reactivating the CIA machinery pathway in GSCs. Functionally, inhibiting PTEN C211 succination by reexpressing a PTEN C211S mutant, depleting ADSL by shRNAs, or consuming fumarate by the US Food and Drug Administration-approved prescription drug N-acetylcysteine (NAC) impaired GSC maintenance. Reexpressing PTEN C211S or treating with NAC sensitized GSC-derived brain tumors to temozolomide and irradiation, the standard-of-care treatments for patients with glioblastoma, by slowing CIA machinery-mediated DNA damage repair. These findings reveal an immediately practicable strategy to target GSCs to treat glioblastoma by combination therapy with repurposed NAC.

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).

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.