Electrically Induced Crystal Field Distortion in a Ferroelectric Perovskite Revealed by Electron Paramagnetic Resonance.

The magnetoelectric material has attracted multidisciplinary interest in the past decade for its potential to accommodate various functions. Especially, the external electric field can drive the quantum behaviors of such materials via the spin-electric coupling effect, with the advantages of high spatial resolution and low energy cost. In this work, the spin-electric coupling effect of Mn2+-doped ferroelectric organic-inorganic hybrid perovskite [(CH3)3NCH2Cl]CdCl3 with a large piezoelectric effect was investigated. The electric field manipulation efficiency for the allowed transitions was determined by the pulsed electron paramagnetic resonance. The orientation-included Hamiltonian of the spin-electric coupling effect was obtained via simulating the angle-dependent electric field modulated continuous-wave electron paramagnetic resonance. The results demonstrate that the applied electric field affects not only the principal values of the zero-field splitting tensor but also its principal axis directions. This work proposes and exemplifies a route to understand the spin-electric coupling effect originating from the crystal field imposed on a spin ion being modified by the applied electric field, which may guide the rational screening and designing of hybrid perovskite ferroelectrics that satisfy the efficiency requirement of electric field manipulation of spins in quantum information applications.

MOTAI: A Novel Method for the Study of O-GalNAcylation and Complex O-Glycosylation in Cancer.

The Tn antigen, an immature truncated O-glycosylation, is a promising biomarker for cancer detection and diagnosis. However, reliable methods for analyzing O-GalNAcylation and complex O-glycosylation are lacking. Here, we develop a novel method, MOTAI, for the sequential analysis of O-glycosylation using different O-glycoproteases. MOTAI conjugates glycopeptides on a solid support and releases different types of O-glycosylation through sequential enzymatic digestion by O-glycoproteases, including OpeRATOR and IMPa. Because OpeRATOR has less activity on O-GalNAcylation, MOTAI enriches O-GalNAcylation for subsequent analysis. We demonstrate the effectiveness of MOTAI by analyzing fetuin O-glycosylation and Jurkat cell lines. We then apply MOTAI to analyze colorectal cancer and benign colorectal polyps. We identify 32 Tn/sTn-glycoproteins and 43 T/sT-glycoproteins that are significantly increased in tumor tissues. Gene Ontology analysis reveals that most of these proteins are ECM proteins involved in the adhesion process of the intercellular matrix. Additionally, the protein disulfide isomerase CRELD2 has a significant difference in Tn expression, and the abnormally glycosylated T345 and S349 O-glycosylation sites in cancer group samples may promote the secretion of CRELD2 and ultimately tumorigenesis through ECM reshaping. In summary, MOTAI provides a powerful new tool for the in-depth analysis of O-GalNAcylation and complex O-glycosylation. It also reveals the upregulation of Tn/sTn-glycoproteins in colorectal cancer, which may provide new insights into cancer biology and biomarker discovery.

Half-Sandwich Iridium Complexes: A Recyclable and Stable Catalyst for Dehydrogenation of Alcohols to Carboxylic Acids.

A series of acylhydrazone-based N,N-chelate half-sandwich iridium complexes have been synthesized through a facile route in good yields. The dehydrogenation of a series of aromatic and aliphatic primary alcohols to corresponding carboxylic acids has been accomplished catalyzed by the prepared air stable iridium complexes under mild reaction conditions. Carboxylic acids were obtained in high yields under open flask condition with broad substrates and good tolerance to sensitive functional groups. Such a half-sandwich iridium catalyst system exhibited high catalytic activity and stability, and a high TOF of 316.7 h-1 could be achieved with a catalyst loading as low as 0.05 mol %. Furthermore, the sustainable catalyst could be reused at least five times without obviously losing its activity, highlighting its potential application in industry. Molecular structure of iridium complex 1 was confirmed by single-crystal X-ray analysis.

Fragmentation Patterns of Phenolic C-Glycosides in Mass Spectrometry Analysis.

BACKGROUND: Many phenolic C-glycosides possess nutritional benefits and pharmacological efficacies. However, the MS/MS fragmentation pattern of phenolic C-glycosides analysis is understudied. This paper aims to determine the MS/MS fragmentation patterns of phenolic C-glycosides. METHOD: Ten compounds with different sugar moieties, aglycones, and substitutes were analyzed to determine the impact of these structural features on MS/MS fragmentation using UPLC-QTOF-MS analysis. RESULTS: The results showed that water loss followed by RDA reaction and alpha cleavage in the C-C bonded sugar moieties are the major fragmentation pathways. Additionally, the sugar cleavage was not affected by the skeleton and the substitute of the aglycones. These results suggested that the fragmentation patterns of phenolic C-glycosides differ from those in the O-glycosides, where the O-C glycosidic bond is the most cleavage-liable bond in MS/MS analysis. CONCLUSIONS: These MS/MS fragmentation patterns can be used for the identification of C-glycosides from dietary components and herbal medicine as well as developing robust methods using MRM methods to quantify C-glycosides.

Screening of ent-copalyl diphosphate synthase and metabolic engineering to achieve de novo biosynthesis of ent-copalol in Saccharomyces cerevisiae.

The diterpene ent-copalol is an important precursor to the synthesis of andrographolide and is found only in green chiretta (Andrographis paniculata). De novo biosynthesis of ent-copalol has not been reported, because the catalytic activity of ent-copalyl diphosphate synthase (CPS) is very low in microorganisms. In order to achieve the biosynthesis of ent-copalol, Saccharomyces cerevisiae was selected as the chassis strain, because its endogenous mevalonate pathway and dephosphorylases could provide natural promotion for the synthesis of ent-copalol. The strain capable of synthesizing diterpene geranylgeranyl pyrophosphate was constructed by strengthening the mevalonate pathway genes and weakening the competing pathway. Five full-length ApCPSs were screened by transcriptome sequencing of A. paniculata and ApCPS2 had the best activity and produced ent-CPP exclusively. The peak area of ent-copalol was increased after the ApCPS2 saturation mutation and its configuration was determined by NMR and ESI-MS detection. By appropriately optimizing acetyl-CoA supply and fusion-expressing key enzymes, 35.6 mg/L ent-copalol was generated. In this study, de novo biosynthesis and identification of ent-copalol were achieved and the highest titer ever reported. It provides a platform strain for the further pathway analysis of andrographolide and derivatives and provides a reference for the synthesis of other pharmaceutical intermediates.

Multichannel focused higher-order Poincaré sphere beam generation based on a dielectric geometric metasurface.

Focused vector beams (VBs) are important topic in the areas of light field manipulation. Geometric metasurfaces provide a convenient platform to facilitate the generation of focused VBs. In this study, we propose a dielectric geometric metasurface to generate multichannel focused higher-order Poincaré sphere (HOP) beams. With identical meta-atoms of half-wave plate, the metasurface comprises two sub-metasurfaces, and each of them includes two sets of rings related to Fresnel zones. For meta-atoms on each set of rings, the hyperbolic geometric phase profile is configured so that the mirror-symmetrical position-flip of the off-axis focal point is enabled under the chirality switch of the illuminating circular polarization. With the design of helical geometric phase profiles for the two sets of rings, a sub-metasurface generate two HOP beams at the symmetrical two focal points. The performance of the two sub-metasurfaces enables the metasurface with four sets of rings to generate the array of four HOP beams. The proposed method was validated by theoretical analyses, numerical simulation and experimental conduction. This research would be significant in miniaturizing and integrating optical systems involving applications of VB generations and applications.

Restricted and epitaxial growth of MnO2-x nano-flowers in/out carbon nanofibers for long-term cycling stability supercapacitor electrodes.

Carbon nanofibers (CFs) have been widely applied as electrodes for energy storage devices owing to the features of increased contact area between electrodes and electrolyte, and shortened transmission route of electrons. However, the poor electrochemical activity and severe waste of space hinder their further application as supercapacitors electrodes. In this work, MnO2-x nanoflowers restricted and epitaxial growth in/out carbon nanofibers (MnO2/MnO@CF) were prepared as excellent electrode materials for supercapacitors. With the synergistic effect of uniquely designed structure and the introduction of MnO and MnO2 nanoflowers, the prepared interconnected MnO2/MnO@CF electrodes demonstrated satisfactory electrochemical performance. Furthermore, the MnO2/MnO@CF//activated carbon (AC) asymmetric supercapacitor offered an outstanding long-term cycle stability. Besides, kinetic analysis of MnO2/MnO@CF-90 was conducted and the diffusion-dominated storage mechanism was well-revealed. This concept of "internal and external simultaneous decoration" with different valence states of manganese oxides was proven to improve the electrochemical performance of carbon nanofibers, which could be generalized to the preparation and performance improvement of other fiber-based electrodes.

Research on the loading and release kinetics of the vincristine sulfate liposomes and its anti-breast cancer activity.

Vincristine (VCR), as a cytotoxic drug, is used clinically to treat acute lymphatic leukemia and breast cancer, and commonly used clinically as vincristine sulfate (VCRS). However, its clinical use is limited by unpredictable pharmacologic characteristics, a narrow therapeutic index, and neurotoxicity. The pH gradient method was used for active drug loading of VCRS, and the process route mainly includes the preparation of blank liposomes and drug-loaded liposomes. VCRS liposomes had suitable particle size, high encapsulation efficiency and good stability. The loading and release kinetics of VCRS liposomes were explored. By calculating the changes of encapsulation efficiency with time at different temperatures, it was confirmed that the drug-loading process of liposomes exhibited a first-order kinetic feature, and the activation energy required for the reaction was determined as 20.6 kcal/mol. The release behavior at different pH was also investigated, and it was demonstrated that the release behavior conformed to the first-order model, suggesting that the release mechanism of VCRS was simple transmembrane diffusion. VCRS liposomes also enhanced in vitro and in vivo antitumor activity. Thus, VCRS liposomes showed great potential for VCRS delivery, and the loading and release kinetics were well researched to provide a reference for investigating active drug loading liposomes.

Discovery and engineering of ChCas12b for precise genome editing.

Many clustered regularly interspaced short palindromic repeat and CRISPR-associated protein 12b (CRISPR-Cas12b) nucleases have been computationally identified, yet their potential for genome editing remains largely unexplored. In this study, we conducted a GFP-activation assay screening 13 Cas12b nucleases for mammalian genome editing, identifying five active candidates. Candidatus hydrogenedentes Cas12b (ChCas12b) was found to recognize a straightforward WTN (W = T or A) proto-spacer adjacent motif (PAM), thereby dramatically expanding the targeting scope. Upon optimization of the single guide RNA (sgRNA) scaffold, ChCas12b exhibited activity comparable to SpCas9 across a panel of nine endogenous loci. Additionally, we identified nine mutations enhancing ChCas12b specificity. More importantly, we demonstrated that both ChCas12b and its high-fidelity variant, ChCas12b-D496A, enabled allele-specific disruption of genes harboring single nucleotide polymorphisms (SNPs). These data position ChCas12b and its high-fidelity counterparts as promising tools for both fundamental research and therapeutic applications.

Rehmmannia glutinosa polysaccharide exerts antiviral activity against pseudorabies virus and antioxidant activity.

Pseudorabies virus (PRV) is an important pathogen harming the global pig industry. Vaccines available for swine cannot protect against PRV completely. Furthermore, no antiviral drugs are available to treat PRV infections. Rehmmannia glutinosa polysaccharide (RGP) possesses several medicinal properties. However, its antiviral activity is not reported. In the present study, we found that RGP can inhibit PRV/XJ5 infection by western blotting, immunofluorescent assay (IFA), and TCID50 assay quantitative polymerase chain reaction (qPCR). We revealed RGP can inhibit virus adsorption and invasion into PK-15 cells in a dose-dependent manner via western blotting, IFA, TCID50 assay, and quantitative polymerase chain reaction (qPCR), and suppressed PRV/XJ5 replication through western blotting, and qPCR. Additionally, it also reduced PRV/XJ5-induced ROS, lipid oxidation, and improved SOD levels in PK-15 cells, which was observed by using corresponding test kits. To conclude, our findings suggest that RGP might be a novel therapeutic agent for preventing and controlling PRV infection and antioxidant agent.

Ultra-pH-sensitive nanoparticle of gambogenic acid for tumor targeting therapy via anti-vascular strategy plus immunotherapy.

Although the combination of anti-vascular strategy plus immunotherapy has emerged as the optimal first-line treatment of hepatocellular carcinoma, lack of tumor targeting leads to low antitumor efficacy and serious side effect. Here, we report an ultra-pH-sensitive nanoparticle of gambogenic acid (GNA) encapsulated by poly(ethylene glycol)-poly(2-azepane ethyl methacrylate) (PEG-PAEMA) for tumor-targeting combined therapy of anti-vascular strategy plus immunotherapy. PEG-PAEMA-GNA nanoparticle was quite stable at pH 7.4 for 30 d. In contrast, it exerted size shrinkage, charge reversal and the release of GNA at pH 6.7 within 24 h. Moreover, PEG-PAEMA-GNA significantly enhanced the anti-vascular activity, membrane-disruptive capability and pro-apoptosis when pH changed from 7.4 to 6.7. Western blot analysis exhibits that PEG-PAEMA and its GNA nanoparticle facilitated the phosphorylation of STING protein. In vivo assays show that PEG-PAEMA-GNA not only displayed much higher tumor inhibition of 92 % than 37 % of free GNA, but also inhibited tumor vasculature, promoted the maturation of dendritic cells and recruited more cytotoxic t-lymphocytes for sufficient anti-vascular therapy and immunotherapy. All these results demonstrate that PEG-PAEMA-GNA displayed tumor-targeting combined treatment of anti-vascular therapy and immunotherapy. This study offers a simple and novel method for the combination of anti-vascular therapy and immunotherapy with high selectivity towards tumor.

BICC1 drives pancreatic cancer stemness and chemoresistance by facilitating tryptophan metabolism.

Pancreatic adenocarcinoma is the fourth leading cause of malignancy-related deaths, with rapid development of drug resistance driven by pancreatic cancer stem cells. However, the mechanisms sustaining stemness and chemotherapy resistance in pancreatic ductal adenocarcinoma (PDAC) remain unclear. Here, we demonstrate that Bicaudal C homolog 1 (BICC1), an RNA binding protein regulating numerous cytoplasmic mRNAs, facilitates chemoresistance and stemness in PDAC. Mechanistically, BICC1 activated tryptophan catabolism in PDAC by up-regulating indoleamine 2,3-dioxygenase-1 (IDO1) expression, a tryptophan-catabolizing enzyme. Increased levels of tryptophan metabolites contribute to NAD+ synthesis and oxidative phosphorylation, leading to a stem cell-like phenotype. Blocking BICC1/IDO1/tryptophan metabolism signaling greatly improves the gemcitabine (GEM) efficacy in several PDAC models with high BICC1 level. These findings indicate that BICC1 is a critical tryptophan metabolism regulator that drives the stemness and chemoresistance of PDAC and thus a potential target for combinatorial therapeutic strategy against chemoresistance.

A novel sustainable immunoassay for sensitive detection of atrazine based on the anti-idiotypic nanobody and recombinant full-length antibody.

Immunoassays have been widely used to determine small-molecule compounds in food and the environment, meeting the challenge of obtaining false positive or negative results because of the variance in the batches of antibodies and antigens. To resolve this problem, atrazine (ATR) was used as a target, and anti-idiotypic nanobodies for ATR (AI-Nbs) and a recombinant full-length antibody against ATR (ATR-rAb) were prepared for the development of a sustainable enzyme-linked immunosorbent assay (ELISA). AI-Nb-7, AI-Nb-58, and AI-Nb-66 were selected from an immune phage display library. ATR-rAb was produced in mammalian HEK293 (F) cells. Among the four detection methods explored, the assay using AI-Nb-66 as a coating antigen and ATR-rAb as a detection reagent yielded a half maximal inhibitory concentration (IC50) of 1.66 ng mL-1 for ATR and a linear range of 0.35-8.73 ng mL-1. The cross-reactivity of the assay to ametryn was 64.24%, whereas that to terbutylazine was 38.20%. Surface plasmon resonance (SPR) analysis illustrated that these cross-reactive triazine compounds can bind to ATR-rAb to varying degrees at high concentrations; however, the binding/dissociation kinetic curves and the response values at the same concentration are different, which results in differences in cross-reactivity. Homology modeling and molecular docking revealed that the triazine ring is vital in recognizing triazine compounds. The proposed immunoassay exhibited acceptable recoveries of 84.40-105.36% for detecting fruit, vegetables, and black tea. In conclusion, this study highlights a new strategy for developing sustainable immunoassays for detecting trace pesticide contaminants.

Engineering of a high-fidelity Cas12a nuclease variant capable of allele-specific editing.

CRISPR-Cas12a, often regarded as a precise genome editor, still requires improvements in specificity. In this study, we used a GFP-activation assay to screen 14 new Cas12a nucleases for mammalian genome editing, successfully identifying 9 active ones. Notably, these Cas12a nucleases prefer pyrimidine-rich PAMs. Among these nucleases, we extensively characterized Mb4Cas12a obtained from Moraxella bovis CCUG 2133, which recognizes a YYN PAM (Y = C or T). Our biochemical analysis demonstrates that Mb4Cas12a can cleave double-strand DNA across a wide temperature range. To improve specificity, we constructed a SWISS-MODEL of Mb4Cas12a based on the FnCas12a crystal structure and identified 8 amino acids potentially forming hydrogen bonds at the target DNA-crRNA interface. By replacing these amino acids with alanine to disrupt the hydrogen bond, we tested the influence of each mutation on Mb4Cas12a specificity. Interestingly, the F370A mutation improved specificity with minimal influence on activity. Further study showed that Mb4Cas12a-F370A is capable of discriminating single-nucleotide polymorphisms. These new Cas12a orthologs and high-fidelity variants hold substantial promise for therapeutic applications.

Multi-Scenario Validation and Assessment of a Particulate Matter Sensor Monitor Optimized by Machine Learning Methods.

OBJECTIVE: The aim was to evaluate and optimize the performance of sensor monitors in measuring PM2.5 and PM10 under typical emission scenarios both indoors and outdoors. METHOD: Parallel measurements and comparisons of PM2.5 and PM10 were carried out between sensor monitors and standard instruments in typical indoor (2 months) and outdoor environments (1 year) in Shanghai, respectively. The optimized validation model was determined by comparing six machining learning models, adjusting for meteorological and related factors. The intra- and inter-device variation, measurement accuracy, and stability of sensor monitors were calculated and compared before and after validation. RESULTS: Indoor particles were measured in a range of 0.8-370.7 µg/m3 and 1.9-465.2 µg/m3 for PM2.5 and PM10, respectively, while the outdoor ones were in the ranges of 1.0-211.0 µg/m3 and 0.0-493.0 µg/m3, correspondingly. Compared to machine learning models including multivariate linear model (ML), K-nearest neighbor model (KNN), support vector machine model (SVM), decision tree model (DT), and neural network model (MLP), the random forest (RF) model showed the best validation after adjusting for temperature, relative humidity (RH), PM2.5/PM10 ratios, and measurement time lengths (months) for both PM2.5 and PM10, in indoor (R2: 0.97 and 0.91, root-mean-square error (RMSE) of 1.91 µg/m3 and 4.56 µg/m3, respectively) and outdoor environments (R2: 0.90 and 0.80, RMSE of 5.61 µg/m3 and 17.54 µg/m3, respectively), respectively. CONCLUSIONS: Sensor monitors could provide reliable measurements of PM2.5 and PM10 with high accuracy and acceptable inter and intra-device consistency under typical indoor and outdoor scenarios after validation by RF model. Adjusting for both climate factors and the ratio of PM2.5/PM10 could improve the validation performance.

Genome-wide identification and expression analysis of the universal stress protein (USP) gene family in Arabidopsis thaliana, Zea mays, and Oryza sativa.

The Universal Stress Protein (USP) primarily participates in cellular responses to biotic and abiotic stressors, playing a pivotal role in plant growth, development, and Stress responses to adverse environmental conditions. Totals of 23, 26 and 26 USP genes were recognized in Arabidopsis thaliana, Zea mays, and Oryza sativa, respectively. According to USP genes physicochemical properties, proteins from USP I class were identified as hydrophilic proteins with high stability. Based on phylogenetic analysis, USP genes family were classified into nine groups, USP II were rich in motifs. Additionally, members of the same subgroup exhibited similar numbers of introns/exons, and shared conserved domains, indicating close evolutionary relationships. Motif analysis results demonstrated a high degree of conservation among USP genes. Chromosomal distribution suggested that USP genes might have undergone gene expansion through segmental duplication in Arabidopsis thaliana, Zea mays, and Oryza sativa. Most Ka/Ks ratios were found to be less than 1, suggesting that USP genes in Arabidopsis thaliana, Zea mays, and Oryza sativa have experienced purifying selection. Expression profile analysis revealed that USP genes primarily respond to drought stress in Oryza sativa, temperature, and drought stress in Zea mays, and cold stress in Arabidopsis thaliana. Gene collinearity analysis can reveal correlations between genes, aiding subsequent in-depth investigations. This study sheds new light on the evolution of USP genes in monocots and dicots and lays the foundation for a better understanding of the biological functions of the USP genes family.

Characterization of a novel multifunctional ß-glucosidase/xylanase/feruloyl esterase and its effects on improving the quality of Longjing tea.

Herein, a novel multifunctional enzyme ß-glucosidase/xylanase/feruloyl esterase (GXF) was constructed by fusion of ß-glucosidase and bifunctional xylanase/feruloyl esterase. The activities of ß-glucosidase, xylanase, feruloyl esterase and acetyl xylan esterase displayed by GXF were 67.18 %, 49.54 %, 38.92 % and 23.54 %, respectively, higher than that of the corresponding single functional enzymes. Moreover, the GXF performed better in enhancing aroma and quality of Longjing tea than the single functional enzymes and their mixtures. After treatment with GXF, the grassy and floral odors of tea infusion were significantly improved. Moreover, GXF treatment could improve concentrations of flavonoid aglycones of myricetin, kaempferol and quercetin by 68.1-, 81.42- and 77.39-fold, respectively. In addition, GXF could accelerate the release of reducing sugars, ferulic acid and xylo-oligosaccharides by 9.48-, 8.25- and 4.11-fold, respectively. This multifunctional enzyme may have potential applications in other fields such as food production and biomass degradation.

Human papillomavirus infection and the risk of cancer at specific sites other than anogenital tract and oropharyngeal region: an umbrella review.

BACKGROUND: Despite numerous studies having evaluated the associations between human papillomavirus (HPV) infection and risk of specific cancers other than anogenital tract and oropharyngeal, the findings are inconsistent and the quality of evidence has not been systematically quantified. We aimed to summarise the existing evidence as well as to evaluate the strength and credibility of these associations. METHODS: We conducted an umbrella review of systematic reviews and meta-analyses of observational studies. PubMed, EMBASE, and Web of Science were searched from inception to March 2024. Studies with systematic reviews and meta-analyses that examined associations between HPV or HPV-associated genotypes infection and specific cancers were eligible for this review. The quality of the methodology was evaluated using A Measurement Tool to Assess systematic Reviews (AMSTAR). The credibility of the evidence was assessed using GRADE. The protocol was preregistered with PROSPERO (CRD42023439070). FINDINGS: The umbrella review identified 31 eligible studies reporting 87 associations with meta-analytic estimates, including 1191 individual studies with 336,195 participants. Of those, 29 (93.5%) studies were rated as over moderate quality by AMSTAR. Only one association indicating HPV-18 infection associated with an increased risk of breast cancer (odds ratio [OR] = 3.48, 95% confidence interval [CI] = 2.24-5.41) was graded as convincing evidence. There were five unique outcomes identified as highly suggestive evidence, including HPV infection increased the risk of oral squamous cell carcinoma (OR = 7.03, 95% CI = 3.87-12.76), oesophageal cancer (OR = 3.32, 95% CI = 2.54-4.34), oesophageal squamous cell carcinoma (OR = 2.69, 95% CI = 2.05-3.54), lung cancer (OR = 3.60, 95% CI = 2.59-5.01), and breast cancer (OR = 6.26, 95% CI = 4.35-9.00). According to GRADE, one association was classified as high, indicating that compared with the controls in normal tissues, HPV infection was associated with an increased risk of breast cancer. INTERPRETATION: The umbrella review synthesised up-to-date observational evidence on HPV infection with the risk of breast cancer, oral squamous cell carcinoma, oesophageal cancer, oesophageal squamous cell carcinoma, and lung cancer. Further larger prospective cohort studies are needed to verify the associations, providing public health recommendations for prevention of disease. FUNDING: National Key Research and Development Program of China, Natural Science Foundation of China, Outstanding Scientific Fund of Shengjing Hospital of China Medical University, and 345 Talent Project of Shengjing Hospital of China Medical University.