bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppressing UBE2N ameliorates Alzheimer's disease pathology through the clearance of amyloid beta
Authors: Zhang Chen , Jia Qingqing , Zhu Longhong , Hou Junqi , Wang Xiang , Li Dandan , Zhang Jiawei , Zhang Yiran , Yang Su , Tu Zhuchi , Yan Xiao‐Xin , Yang Weili , Li Shihua , Li Xiao‐Jiang , Yin Peng 
Published: July 2024

AbstractINTRODUCTIONAging is one of the risk factors for the early onset of Alzheimer's disease (AD). We previously discovered that the age‐dependent increase in Ubiquitin Conjugating Enzyme E2 N (UBE2N) plays a role in the accumulation of misfolded proteins through K63 ubiquitination, which has been linked to AD pathogenesis. However, the impact of UBE2N on amyloid pathology and clearance has remained unknown.RESULTSWe observed the elevated UBE2N during the amyloid beta (Aβ) generation in the brains of 5×FAD, APP/PS1 mice, and patients with AD, in comparison to healthy individuals. UBE2N overexpression exacerbated amyloid deposition in 5×FAD mice and senescent monkeys, whereas knocking down UBE2N via CRISPR/Cas9 reduced Aβ generation and cognitive deficiency. Moreover, pharmacological inhibition of UBE2N ameliorated Aβ pathology and subsequent transcript defects in 5×FAD mice.DISCUSSIONWe have discovered that age‐dependent expression of UBE2N is a critical regulator of AD pathology. Our findings suggest that UBE2N could serve as a potential pharmacological target for the advancement of AD therapeutics.Highlights
Ubiquitin Conjugating Enzyme E2 N (UBE2N) level was elevated during amyloid beta (Aβ) deposition in AD mouse and patients' brains.
UBE2N exacerbated Aβ generation in the AD mouse and senescent monkey.
Drug inhibition of UBE2N ameliorated Aβ pathology and cognitive deficiency.
Fabrication and characteristics of functional hydrogels based on dopamine‐grafted gelatin and oxyglucan with incorporation of dipotassium glycyrrhizinate potential for wound dressings
Authors: Nie Lei , Ding Xiaoyue , Zhang Han , Li Xinran , Li Man , Ding Peng , Okoro Oseweuba Valentine , Podstawczyk Daria , Sun Yanfang , Jiang Guohua , Shavandi Amin 
Published: July 2024

AbstractHydrogel have been widely used to promote skin tissue regeneration and accelerate wound healing. The development of injectable hydrogels with multi‐functional integration is a priority, especially with antibacterial properties and cytocompatibility. Here, we reported a simple, and versatile method to fabricate a functional hydrogel with potential for wound dressing applications. The dopamine‐grafted gelatin (GT‐DA) and oxidized dextran (oxyglucan, ODex) were synthesized, and dipotassium glycyrrhizinate (DG) was in situ incorporated to fabricate the composite hydrogels (GDO) through the Schiff base reaction. SEM images revealed that hydrogel has a porous structure. By increasing the ratio of GT‐DA to ODex from 1 to 4, the storage modulus (G') and hydrogel network stability nearly doubled, reaching 900 Pa and 220% strain, respectively. The enhancement in mechanical properties could be attributed to the higher cross‐linking density resulting from increased Schiff base bonds in the GDO hydrogels. Furthermore, the GDO hydrogel exhibited antioxidant activity and antibacterial effects on Escherichia coli and Staphylococcus aureus. Moreover, the hydrogel demonstrated cytocompatibility after culturing with human umbilical vein endothelial cells (HUVECs). The results proved that the fabricated GDO hydrogels have the potential to be used as wound dressings.
Surface modification of polylactide films and their hydrolytic degradation performances in artificial seawater
Authors: Yao Lihui , Li Yuzhu , Li Ya , Wang Yajuan , Wang Linghui , Qiu Dan , Weng Yunxuan 
Published: July 2024

AbstractBenzophenone (BP) and N‐vinylpyrrolidone (NVP) were used to modify the surface of polylactide (PLA) films by UV grafting method. The effects of light distance, temperature, reaction time, and modifier concentration on the structure and properties of PLA films were investigated by Fourier transform infrared spectroscopy, X‐ray photoelectron spectroscopy (XPS), nuclear magnetic resonance spectroscopy, differential scanning calorimetry (DSC), and universal testing machine (UTM). With BP and NVP UV grafting, the hydrophilicity of PLA films is improved, but their thermal and mechanical properties are reduced under different surface modification condition. Base on the principle of good surface hydrophilicity, better mechanical and thermal properties, the hydrolytic degradation performance of modified PLA films in artificial seawater at 70°C was studied by scanning electron microscopy, XPS and DSC. The research results show that the degradation of modified PLA films mainly occurs in the amorphous region, and the degradation process conforms to surface hydrolysis mechanism. The grafting modification of NVP is better than BP to accelerate the degradation process of PLA films in artificial seawater. The degradation of modified PLA undergoes water molecule erosion and autocatalytic degradation reaction. The degradation of BP‐PLA obeys the first‐order kinetics in part, while the degradation of NVP‐PLA is more complex. Therefore, surface hydrophilicity modification is an effective technique for improving the degradability of PLA.
Preparation of lanthanide aluminate‐encapsulated silica nanoparticles toward long‐persistent photoluminescent polymer paint with superhydrophobic and anticorrosion properties
Authors: Al‐Senani Ghadah M. , Al‐Qahtani Salhah D. 
Published: July 2024

AbstractSmart afterglow paints can function as energy‐saving products that are able to persist lighting in the dark. Additionally, polyurethane paints (PURPs) have shown some limitations, including weak adhesion, poor mechanical performance, poor corrosion, and low water resistance as compared with solvent‐based paints. Herein, nanoparticles of lanthanide aluminate (NLA; 16–24 nm) were mixed with polyurethane and silica to develop novel photoluminescent nanocomposite paints. A precursor of NLA‐encapsulated silica nanoparticles (NLA@Silica; 200–225 nm) can be described as a SiO2‐coated NLA pigment prepared by the heterogeneous precipitation method. Steel was coated with nanocomposite paints made of PURP, silica, and NLA. Using emission spectra and Commission Internationale de l'Eclairage (CIE) Lab coordinates, the coloring and transparency of painted films were investigated. Upon excitation at 365 nm, the UV‐irradiation of transparent painted films showed green emission at 518 nm. The hydrophobic activity and hardness properties were examined. Using electrochemical impedance spectroscopy (EIS), the anticorrosion of coatings applied to mild steel was studied. Improved anticorrosion characteristics were observed due to the fluorescence of NLA@Silica in the applied coatings. The optimal long‐lasting luminous characteristics were observed for nanocomposite films containing 12.5% of NLA@Silica.
Cloning and characterization of the histone variant gene H2A.Z in Bombyx mori
Authors: Mei Jun , Xu Kunling , Huang Yuyi , Zhang Jingwei , Qian Qitao , Dong Jia , Tong Fudan , Yu Wei , Miao Meng 
Published: July 2024

AbstractH2A.Z, the most evolutionarily conserved variant of histone H2A, plays a pivotal role in chromatin remodeling and contributes significantly to gene transcription and genome stability. However, the role of H2A.Z in the silkworm (Bombyx mori) remains unclear. In this study, we cloned the BmH2A.Z from B. mori. The open reading frame of BmH2A.Z is 390 bp, encoding 129 amino acids, with a confirmed molecular weight of 13.4 kDa through prokaryotic expression analysis. Sequence analysis revealed that BmH2A.Z has a conserved H2A.Z domain and is closely related to the systemic evolution of other known H2A.Zs. The expression profile of BmH2A.Z at various developmental stages of the B. mori exhibited the highest expression level in the 1st instar, followed by the grain stage and the 2nd instar, and the lowest expression level in the moth. The highest transcript level of BmH2A.Z was observed in the head, with relatively lower levels detected in the blood than in the other tissues under consideration. In addition, the upregulation of BmH2A.Z resulted in the amplified expression of B. mori nucleopolyhedrovirus (BmNPV) genes, thus facilitating the proliferation of BmNPV. This study establishes a foundation for investigating the role of BmH2A.Z in B. mori and its participation in virus‐host interactions.
Skeletal Muscle Composition, Power, and Mitochondrial Energetics in Older Men and Women With Knee Osteoarthritis
Authors: Distefano Giovanna , Harrison Stephanie , Lynch John , Link Thomas M. , Kramer Philip A. , Ramos Sofhia V. , Mau Theresa , Coen Paul M. , Sparks Lauren M. , Goodpaster Bret H. , Cawthon Peggy M. , Cauley Jane A. , Lane Nancy E. 
Published: July 2024

ObjectiveOur objective was to investigate the overall and sex‐specific relationships between the presence and severity of knee osteoarthritis (KOA) and muscle composition, power, and energetics in older adults.MethodsMale and female patients (n = 655, mean ± SD age 76.1 ± 4.9 years; 57% female) enrolled in the Study of Muscle, Mobility, and Aging completed standing knee radiographs and knee pain assessments. Participants were divided into three groups using Kellgren‐Lawrence grade (KLG) of KOA severity (0–1, 2, or 3–4). Outcome measures included whole‐body muscle mass, thigh fat‐free muscle (FFM) volume and muscle fat infiltration (MFI), leg power, specific power (power normalized to muscle volume), and muscle mitochondrial energetics.ResultsOverall, the presence and severity of KOA is associated with greater MFI, lower leg power and specific power, and reduced oxidative phosphorylation (P trend < 0.036). Sex‐specific analysis revealed reduced energetics only in female patients with KOA (P trend < 0.007) compared to female patients without KOA. In models adjusted for age, sex, race, nonsteroidal anti‐inflammatory drug administration, site or technician, physical activity, height, and participants with abdominal adiposity with KLG 3 to 4 had greater MFI (mean 0.008%, 95% confidence interval [CI] 0.004%–0.011%) and lower leg power (mean −51.56 W, 95% CI −74.03 to −29.10 W) and specific power (mean −5.38 W/L, 95% CI −7.31 to −3.45 W/L) than those with KLG 0 to 1. No interactions were found between pain and KLG status. Among those with KOA, MFI and oxidative phosphorylation were associated with thigh FFM volume, leg power, and specific power.ConclusionMuscle health is associated with the presence and severity of KOA and differs by sex. Although muscle composition and power are lower in both male and female patients with KOA, regardless of pain status, mitochondrial energetics is reduced only in female patients.
Difluorocarbene‐Promoted O−O Bond Activation of Peroxy Acids for Electrophilic Carboxylation of Boronic Acids
Authors: Niu Hao‐Lin , Luo Peng‐Xi , Zhang Song‐Lin 
Published: July 2024

AbstractIn this study, a difluorocarbene‐promoted O−O bond activation of peroxy acids is developed through the insertion of difluorocarbene into O−H bond. This activation strategy in synergy with O−B coordination with boronic acids/ester greatly polarizes the O−O bond for in‐situ generation of carboxylium species that reacts with the nucleophilic part of boronic acids in a concerted way to produce carboxylic esters. Good efficiency and functional group tolerance are demonstrated. Application of this method to the functionalization of a boronic acid drug used as HSL enzyme inhibitor produces smoothly the ester derivative. This difluorocarbene‐mediated O−O bond activation strategy is conceptually different from traditional radical type methods, and is also complementary to conventional esterification methods with a distinct retro‐synthetic disconnection.
Ethanol‐Based Solution Synthesis of a Functionalized Sulfide Solid Electrolyte: Investigation and Application
Authors: Morino Yusuke , Takase Kentaro , Kamiguchi Kazuhiro , Ito Daisuke 
Published: July 2024

AbstractA sulfide solid electrolyte was synthesized using a solution‐phase approach via the dissolution of Li3PS4 in ethanol followed by heat treatment (90–300 °C). This method yielded an electrolyte with a maximum lithium‐ion conductivity of 1.7×10−5 S cm−1 at 200 °C (down to 25 % of the pristine Li3PS4); however, increasing the heating temperature resulted in a significant decrease in conductivity. Nuclear magnetic resonance spectroscopy revealed the decomposition of the PS43− unit into P2Sx dimers (P2S74− and P2S64−) at high temperatures. X‐ray absorption spectroscopy further confirmed a core‐shell structure in the solution‐phase‐synthesized electrolyte, with an enriched shell of oxygen‐substituted P(S/O)x phases. Both the P2Sx dimers in the core and the oxygen‐rich shell may have contributed to the reduction in lithium‐ion conductivity. Moreover, the oxygen‐rich shell unexpectedly suppressed undesirable side reactions at the solid electrolyte/cathode interface. This study demonstrates the functionalization of solution‐phase synthesis for sulfide solid electrolytes from ethanol, with a trade‐off between conductivity and interface stability. Further optimizing the heat treatment process and shell engineering are promising avenues for enhancing the performance of all‐solid‐state batteries.
Efficient generation of recombinant anti‐HER2 scFv with high yield and purity using a simple method
Authors: Yun Hanool , Kim Sun‐Hee , Kim Seung‐Hee , Park Hae‐Min , Jeong Hee‐Jin 
Published: July 2024

AbstractWe developed a method to produce a soluble form of a single‐chain fragment variable (scFv) targeting human epithelial growth factor receptor 2 (HER2) in Escherichia coli. By optimizing the orientations of the variable heavy (VH) and variable light (VL) domains and the His‐tag, we identified the HL‐His type antibody with the highest HER2‐binding activity. Purification of HL‐His yielded 40.7 mg from a 1 L culture, achieving >99% purity. The limit of detection was determined to be 2.9 ng, demonstrating high production yield, purity, and sensitivity. Moreover, we successfully labeled HER2+ cell lines with fluorescent dye‐conjugated scFv, resulting in a significantly higher observed signal‐to‐background ratio, compared to that of HER2− cell lines. This highlights the potential of these fluorescent scFvs as valuable probes for HER2+ breast cancer diagnostics. Notably, the process for the complete scFv production was streamlined and required only 4–5 days. Additionally, the product maintained its activity after freeze storage, allowing for large‐scale production and a wide range of practical applications.
Development of a marker recyclable CRISPR/Cas9 system for scarless and multigene editing in Fusarium fujikuroi
Authors: Huang Lianggang , Li Ningning , Song Yixin , Gao Jie , Nian Lu , Zhou Junping , Zhang Bo , Liu Zhiqiang , Zheng Yuguo 
Published: July 2024

AbstractIterative metabolic engineering of Fusarium fujikuroi has traditionally been hampered by its low homologous recombination efficiency and scarcity of genetic markers. Thus, the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated proteins (Cas9) system has emerged as a promising tool for precise genome editing in this organism. Some integrated CRISPR/Cas9 strategies have been used to engineer F. fujikuroi to improve GA3 production capabilities, but low editing efficiency and possible genomic instability became the major obstacle. Herein, we developed a marker recyclable CRISPR/Cas9 system for scarless and multigene editing in F. fujikuroi. This system, based on an autonomously replicating sequence, demonstrated the capability of a single plasmid harboring all editing components to achieve 100%, 75%, and 37.5% editing efficiency for single, double, and triple gene targets, respectively. Remarkably, even with a reduction in homologous arms to 50 bp, we achieved a 12.5% gene editing efficiency. By employing this system, we successfully achieved multicopy integration of the truncated 3‐hydroxy‐3‐methyl glutaryl coenzyme A reductase gene (tHMGR), leading to enhanced GA3 production. A key advantage of our plasmid‐based gene editing approach was the ability to recycle selective markers through a simplified protoplast preparation and recovery process, which eliminated the need for additional genetic markers. These findings demonstrated that the single‐plasmid CRISPR/Cas9 system enables rapid and precise multiple gene deletions/integrations, laying a solid foundation for future metabolic engineering efforts aimed at industrial GA3 production.
Quality by design approach to improve quality and decrease cost of in vitro transcription of mRNA using design of experiments
Authors: Boman Jimmy , Marušič Tjaša , Seravalli Tina Vodopivec , Skok Janja , Pettersson Fredrik , Nemec Kristina Šprinzar , Widmark Henrik , Sekirnik Rok 
Published: July 2024

AbstractIn vitro transcription (IVT) reaction is an RNA polymerase‐catalyzed production of messenger RNA (mRNA) from DNA template, and the unit operation with highest cost of goods in the mRNA drug substance production process. To decrease the cost of mRNA production, reagents should be optimally utilized. Due to the catalytic, multicomponent nature of the IVT reaction, optimization is a multi‐factorial problem, ideally suited to design‐of‐experiment approach for optimization and identification of design space. We derived a data‐driven model of the IVT reaction and explored factors that drive process yield (in g/L), including impact of nucleoside triphosphate (NTP) concentration and Mg:NTP ratio on reaction yield and how to optimize the main cost drivers RNA polymerase and DNA template, while minimizing dsRNA formation, a critical quality attribute in mRNA products. We report a methodological approach to derive an optimum reaction design, with which cost efficiency of the reaction was improved by 44%. We demonstrate the validity of the model on mRNA construct of different lengths. Finally, we maximized the yield of the IVT reaction to 24.9 ± 1.5 g/L in batch, thus doubling the highest ever reported IVT yield.
Nano/genetically engineered cells for immunotherapy
Authors: Shen Jingrui , Zhou Yang , Yin Lichen 
Published: July 2024

AbstractImmunotherapy has recently emerged as a promising therapeutic modality for the treatment of various diseases such as cancer, inflammation, autoimmune diseases, and infectious diseases. Despite its potential, immunotherapy faces challenges related to delivery efficiency and off‐target toxicity of immunotherapeutic drugs. Nano drug delivery systems offer improvements in drug biodistribution and release kinetics but still suffer from shortcomings such as high immunogenicity, poor penetration across biological barriers, and insufficient tissue permeability. Targeted delivery of drugs using living cells has become an emerging strategy that can take advantage of the inherent characteristics of cells to deal with the delivery defects of nano delivery systems. Furthermore, cells themselves can be genetically engineered into cellular drugs for enhanced immunotherapy. This review provides an in‐depth exploration of cell‐derived drug carriers, detailing their biological properties, functions, and commonly used drug loading strategies. In addition, the role of genetically modified cells in immunotherapy and their synergistic therapeutic effects with drug delivery are also introduced. By summarizing the main advancements and limitations in the field, this review offers insights into the potential of cell‐based drug delivery systems to address the existing challenges in immunotherapy. The introduction to recent developments and evaluation of ongoing research will pave the way for the optimization and widespread adoption of nano/genetically engineered cells for immunotherapy.
Diagnosis of pregnancy disorder in the first‐trimester patient plasma with Raman spectroscopy and protein analysis
Authors: Mathew Ansuja P. , Cutshaw Gabriel , Appel Olivia , Funk Meghan , Synan Lilly , Waite Joshua , Ghazvini Saman , Wen Xiaona , Sarkar Soumik , Santillan Mark , Santillan Donna , Bardhan Rizia 
Published: July 2024

AbstractGestational diabetes mellitus (GDM) is a pregnancy disorder associated with short‐ and long‐term adverse outcomes in both mothers and infants. The current clinical test of blood glucose levels late in the second trimester is inadequate for early detection of GDM. Here we show the utility of Raman spectroscopy (RS) for rapid and highly sensitive maternal metabolome screening for GDM in the first trimester. Key metabolites, including phospholipids, carbohydrates, and major amino acids, were identified with RS and validated with mass spectrometry, enabling insights into associated metabolic pathway enrichment. Using classical machine learning (ML) approaches, we showed the performance of the RS metabolic model (cross‐validation AUC 0.97) surpassed that achieved with patients' clinical data alone (cross‐validation AUC 0.59) or prior studies with single biomarkers. Further, we analyzed novel proteins and identified fetuin‐A as a promising candidate for early GDM prediction. A correlation analysis showed a moderate to strong correlation between multiple metabolites and proteins, suggesting a combined protein‐metabolic analysis integrated with ML would enable a powerful screening platform for first trimester diagnosis. Our study underscores RS metabolic profiling as a cost‐effective tool that can be integrated into the current clinical workflow for accurate risk stratification of GDM and to improve both maternal and neonatal outcomes.
Matrix metalloproteinase 2‐responsive dual‐drug‐loaded self‐assembling peptides suppress tumor growth and enhance breast cancer therapy
Authors: Ma Jihong , Yang Haiyan , Tian Xue , Meng Fanhu , Zhai Xiaoqing , Li Aimei , Li Chuntao , Wang Min , Wang Guohui , Lu Chunbo , Bai Jingkun 
Published: July 2024

AbstractConventional chemotherapeutic agents are limited by their lack of targeting and penetration and their short retention time, and chemotherapy might induce an immune suppressive environment. Peptide self‐assembly can result in a specific morphology, and the resulting morphological changes are stimuli responsive to the external environment, which is important for drug permeation and retention of encapsulated chemotherapeutic agents. In this study, a polypeptide (Pep1) containing the peptide sequences PLGLAG and RGD that is responsive to matrix metalloproteinase 2 (MMP‐2) was successfully developed. Pep1 underwent a morphological transformation from a spherical structure to aggregates with a high aspect ratio in response to MMP‐2 induction. This drug delivery system (DI/Pep1) can transport doxorubicin (DOX) and indomethacin (IND) simultaneously to target tumor cells for subsequent drug release while extending drug retention within tumor cells, which increases immunogenic cell death and facilitates the immunotherapeutic effect of CD4+ T cells. Ultimately, DI/Pep1 attenuated tumor‐associated inflammation, enhanced the body's immune response, and inhibited breast cancer growth by combining the actions of DOX and IND. Our research offers an approach to hopefully enhance the effectiveness of cancer treatment.