Rapid detection and quantification of melamine, urea, sucrose, water, and milk powder adulteration in pasteurized milk using Fourier transform infrared (FTIR) spectroscopy coupled with modern statistical machine learning algorithms.

There is an evident requirement for a rapid, efficient, and simple method to screen the authenticity of milk products in the market. Fourier transform infrared (FTIR) spectroscopy stands out as a promising solution. This work employed FTIR spectroscopy and modern statistical machine learning algorithms for the identification and quantification of pasteurized milk adulteration. Comparative results demonstrate modern statistical machine learning algorithms will improve the ability of FTIR spectroscopy to predict milk adulteration compared to partial least square (PLS). To discern the types of substances utilized in milk adulteration, a top-performing multiclassification model was established using multi-layer perceptron (MLP) algorithm, delivering an impressive prediction accuracy of 97.4 %. For quantification purposes, bayesian regularized neural networks (BRNN) provided the best results for the determination of both melamine, urea and milk powder adulteration, while extreme gradient boosting (XGB) and projection pursuit regression (PPR) gave better results in predicting sucrose and water adulteration levels, respectively. The regression models provided suitable predictive accuracy with the ratio of performance to deviation (RPD) values higher than 3. The proposed methodology proved to be a cost-effective and fast tool for screening the authenticity of pasteurized milk in the market.

TMEM147: A Promising Cancer Biomarker Associated with Immune Cell Infiltration and Prognosis in LIHC-Insights from a Comprehensive Pan-Cancer Genomic Analysis.

Previous studies have demonstrated the regulatory roles of Transmembrane protein 147 (TMEM147) in various diseases, including cancer. However, systematic pan-cancer analyses investigating the role of TMEM147 in diagnosis, prognosis, and immunological prediction are lacking. An analysis of data from The Cancer Genome Atlas (TCGA) revealed differential TMEM147 expression across various types of cancer as well as within immune and molecular cancer subtypes. Moreover, high TMEM147 expression was associated with poor disease-specific survival (DSS), overall survival (OS), and progression-free interval (PFI) across cancers, suggesting its potential as a prognostic biomarker. Our study further revealed a significant correlation between TMEM147 expression and T helper cell and Tcm cell infiltration in most cancer types. In the case of liver hepatocellular carcinoma (LIHC), the effect of TMEM147 on prognosis varied among different clinical subtypes. Additionally, functional enrichment analysis revealed an association between TMEM147 and metabolic pathways. Finally, experiments on the MIHA cell line and four LIHC cell lines confirmed the role of TMEM147 in promoting liver cancer cell proliferation, further confirming the clinical value of TMEM147 in liver cancer diagnosis. Our findings suggest that TMEM147 may serve as a diagnostic and prognostic biomarker across cancers while also playing a significant role in LIHC.

PI3Kgamma promotes neutrophil extracellular trap formation by noncanonical pyroptosis in abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is one of the most life-threatening cardiovascular diseases; however, effective drug treatments are still lacking. The formation of neutrophil extracellular traps (NETs) has been shown to be crucial trigger of AAA and identifying upstream regulatory targets is thus key to discovering therapeutic agents for AAA. We revealed that phosphoinositide 3-kinase gamma (PI3Kγ) acted as an upstream regulatory molecule, and that PI3Kγ inhibition reduced NET formation and aortic wall inflammation, thereby markedly ameliorating AAA. However, the mechanism of NET formation regulated by PI3Kγ remains unclear. In this study, we showed that PI3Kγ deficiency inactivated the noncanonical pyroptosis pathway, which suppressed downstream NET formation. In addition, PI3Kγ regulation of noncanonical pyroptosis was dependent on cAMP/protein kinase A (cAMP/PKA) signaling. These results clarify the molecular mechanism and crosstalk between PI3Kγ and NETosis in the development of AAA, potentially facilitating the discovery of therapeutic options for AAA.

Quantum Dynamics Studies of the Li + Na2 (V = 0, j = 0) → Na + NaLi Reaction on a New Neural Network Potential Energy Surface.

The ultracold reaction offers a unique opportunity to elucidate the intricate microscopic mechanism of chemical reactions, and the Na2Li system serves as a pivotal reaction system in the investigation of ultracold reactions. In this work, a high-precision potential energy surface (PES) of the Na2Li system is constructed based on high-level ab initio energy points and the neural network (NN) method, and a proper asymptotic functional form is adopted for the long-range interaction, which is suitable for the study of cold or ultracold collisions. Based on the new NN PES, the dynamics of the Li + Na2 (v = 0, j = 0) → Na + NaLi reaction are studied in the collision energy range of 10-7 to 80 cm-1. In the high collision energy range of 8 to 80 cm-1, the dynamics of the reaction is studied using the time-dependent wave packet method and the statistical quantum mechanical (SQM) method. Comparing the results of the two methods, it is found that the SQM method provides a rough description of the product ro-vibrational state distribution but overestimates the integral cross-section values. With the decrease of collision energy, the reaction differential cross section gradually changes from forward-backward symmetric scattering to predominant forward scattering. In the low collision energy range from 10-7 to 8 cm-1, the SQM method is used to study the reaction dynamics, and the rate constant in the Wigner threshold region is estimated to be 2.87 × 10-10 cm3/s.

A neural network potential energy surface of the Li3 system and quantum dynamics studies for the 7Li + 6Li2 → 6Li7Li + 6Li reaction.

A high-precision global potential energy surface (PES) of the Li3 system is constructed based on high-level ab initio calculations, and the root-mean-square error is 5.54 cm-1. The short-range of the PES is fitted by the fundamental invariant neural network (FI-NN) method, while the long-range uses a function with an accurate asymptotic potential energy form, and the two regions are connected by a switching function. Based on the new PES, the statistical quantum-mechanical (SQM) and the time-dependent wave packet (TDWP) methods are used to study the dynamics of 7Li + 6Li2 (v = 0, j = 0) → 6Li7Li + 6Li reactions in the low collision energy region (10-11 to 10-3 cm-1) and the high collision energy region (8 to 800 cm-1), respectively. In the high collision energy region, the calculation results of the SQM method and the TDWP method are inconsistent, indicating that the reaction dynamics does not follow the statistical behavior in the high collision energy region. In addition, we found that the Coriolis coupling effect plays an important role in this reaction. The symmetric forward-backward scattering in the total DCS indicates that the reaction follows the complex-forming reaction mechanism.

The effect of the number of conjugated C=C bonds on the ESIPT and ICT reactions of SNCN derivatives.

The electronic structure of the molecule is significantly influenced by the number of conjugated C=C bonds. In this work, the influence of the conjugated C=C bonds of the SNCN derivatives on the excited state intramolecular proton transfer (ESIPT) and intramolecular charge transfer (ICT) properties are studied by density functional theory (DFT) and time-dependent density functional theory (TDDFT). The calculation level is proved to be reasonable by calculating electronic spectra. The hydrogen bond parameters, infrared vibrational frequency (IR), reduction density gradient (RDG) isosurface, topological analysis and potential energy curves of SNCN derivatives in ground state (S0) and the first excited state (S1) are analyzed. According to theoretical research results, ESIPT reaction has a higher likelihood of occurring in the S1 state. Moreover, the ESIPT reaction becomes more challenging to occur with the number of conjugated C=C bonds rising. Finally, the analyses of the frontier molecular orbitals (FMOs), dipole moment and charge transfer transition confirm that the ICT effect is aided by the increased number of conjugated C=C bonds. This work indicates that the number of conjugated C=C bonds can regulate the ESIPT and ICT processes, which provides guidance for the study of fluorescent groups with similar characteristics.

Substituent effects on the ESIPT process and the potential applications in materials transport field of 2'-aminochalcone derivatives.

This work investigates the different charge transfer characteristics and excited state intramolecular proton transfer process (ESIPT) of 2'-aminochalcones derivatives carrying different electron-withdrawing groups. Four new molecules are designed in the experiment and named as 2c, 3c, 4c and 5c, respectively. (Dyes and Pigments, 2022, 202.) Based on these four molecules, the effect of substituents on the ESIPT process and the charge transfer process are discussed in detail in our work. According to the study of the related parameters at the hydrogen bond site, infrared vibration spectrum, interaction region indicator isosurface (IRI) and scatter plots, it is concluded that the hydrogen bond interaction is enhanced under photoexcitation, and the descending order of the excited state hydrogen bond strength is 3c > 5c > 4c > 2c. The hydrogen bond energy is calculated by atoms in moleculs (AIM) topological analysis and core-valence bifurcation (CVB) index. The potential energy curve reveals the ESIPT mechanism. Frontier molecular orbital and electron-hole analyses explain the reasons for the changes in the ESIPT process at the electronic level. In addition, the ionization potentials (IPa and IPv), affinity energies (EAa and EAv) and reorganization energies are calculated to evaluate the potential application value of organic molecules in material transport field.

Pygo-F773W Mutation Reveals Novel Functions beyond Wnt Signaling in Drosophila.

Pygopus (Pygo) has been identified as a specific nuclear co-activator of the canonical Wingless (Wg)/Wnt signaling pathway in Drosophila melanogaster. Pygo proteins consist of two conserved domains: an N-terminal homologous domain (NHD) and a C-terminal plant homologous domain (PHD). The PHD's ability to bind to di- and trimethylated lysine 4 of histone H3 (H3K4me2/3) appears to be independent of Wnt signaling. There is ongoing debate regarding the significance of Pygo's histone-binding capacity. Drosophila Pygo orthologs have a tryptophan (W) > phenylalanine (F) substitution in their histone pocket-divider compared to vertebrates, leading to reduced histone affinity. In this research, we utilized CRISPR/Cas9 technology to introduce the Pygo-F773W point mutation in Drosophila, successfully establishing a viable homozygous Pygo mutant line for the first time. Adult mutant flies displayed noticeable abnormalities in reproduction, locomotion, heart function, and lifespan. RNA-seq and cluster analysis indicated that the mutation primarily affected pathways related to immunity, metabolism, and posttranslational modification in adult flies rather than the Wnt signaling pathway. Additionally, a reduction in H3K9 acetylation levels during the embryonic stage was observed in the mutant strains. These findings support the notion that Pygo plays a wider role in chromatin remodeling, with its involvement in Wnt signaling representing only a specific aspect of its chromatin-related functions.

Interlayer Fermi Polarons of Excited Exciton States in Quantizing Magnetic Fields.

The study of exciton polarons has offered profound insights into the many-body interactions between bosonic excitations and their immersed Fermi sea within layered heterostructures. However, little is known about the properties of exciton polarons with interlayer interactions. Here, through magneto-optical reflectance contrast measurements, we experimentally investigate interlayer Fermi polarons for 2s excitons in WSe2/graphene heterostructures, where the excited exciton states (2s) in the WSe2 layer are dressed by free charge carriers of the adjacent graphene layer in the Landau quantization regime. First, such a system enables an optical detection of integer and fractional quantum Hall states (e.g., ν = ±1/3, ±2/3) of monolayer graphene. Furthermore, we observe that the 2s state evolves into two distinct branches, denoted as attractive and repulsive polarons, when graphene is doped out of the incompressible quantum Hall gaps. Our work paves the way for the understanding of the excited composite quasiparticles and Bose-Fermi mixtures.

Progress of Antimicrobial Mechanisms of Stilbenoids.

Antimicrobial drugs have made outstanding contributions to the treatment of pathogenic infections. However, the emergence of drug resistance continues to be a major threat to human health in recent years, and therefore, the search for novel antimicrobial drugs is particularly urgent. With a deeper understanding of microbial habits and drug resistance mechanisms, various creative strategies for the development of novel antibiotics have been proposed. Stilbenoids, characterized by a C6-C2-C6 carbon skeleton, have recently been widely recognized for their flexible antimicrobial roles. Here, we comprehensively summarize the mode of action of stilbenoids from the viewpoint of their direct antimicrobial properties, antibiofilm and antivirulence activities and their role in reversing drug resistance. This review will provide an important reference for the future development and research into the mechanisms of stilbenoids as antimicrobial agents.

Conventionality matters in Chinese metaphor but not simile comprehension: evidence from event-related potentials.

Metaphor and simile, two prevalent forms of figurative language widely employed in daily communication, serve as significant research subjects in linguistics. The Career of Metaphor Theory in cognitive linguistics posits that as conventionality increases, the cognitive mechanisms of metaphor comprehension shift from "comparison" to "categorization." In line with this notion, prior electrophysiological investigations have revealed that novel metaphors elicit a stronger N400 brain response compared to conventional metaphors. However, the observed N400 difference between conventional and novel metaphors may merely stem from the familiarity contrast between them, as conventional metaphors are typically more familiar than novel ones. To address this dichotomy, the present study not only compared the N400 responses between conventional and novel metaphors but also between conventional and novel similes. While conventional and novel similes differ in familiarity, similar to conventional and novel metaphors, both are processed via "comparison" mechanisms. The results revealed that novel metaphors elicited larger N400 amplitudes compared to conventional metaphors, aligning with previous findings. In contrast, no significant N400 differences were observed between conventional and novel similes, suggesting that familiarity disparity is unlikely to account for N400 distinctions. Our findings imply that conventional and novel metaphors undergo distinct cognitive processing mechanisms ("comparison" versus "categorization"), thereby providing further empirical validation for the Career of Metaphor Theory.

Population Genetic Assessment Model Reveals Conservation Priorities for Gymnocypris Species Resources on the Qinghai-Tibetan Plateau.

The Qinghai-Tibetan Plateau (QTP) has nurtured a rich diversity of species because of its unique geographical and environmental conditions. Gymnocypris species (subfamily Schizopygopsinae) are primitive fishes that live in the special environment of the plateau, and their evolution and distribution are inseparable from the historical changes of the QTP. Recently, the resources of Gymnocypris species have been decreasing due to habit deterioration and the intensification of human activities. Therefore, the scientific conservation of the genetic resources of Gymnocypris species is urgently required. In this study, we established two models for the priority conservation assessment of germplasm resources of Gymnocypris species on the basis of the genetic diversity and phylogenetic relationships of 674 individuals from eight Gymnocypris species populations. The results show that the Gymnocypris potanini (GPO), Gymnocypris eckloni (GE), and Gymnocypris przewalskii (GPR) populations are the most genetically diverse in terms of combined genetic diversity values and should be prioritized for conservation. In terms of genetic contribution, the GPO, GE, and GPR populations have a positive impact on maintaining the distinctiveness and diversity of the entire Gymnocypris species population and should be prioritized for conservation. However, in terms of different evolutionary clades, the Gymnocypris namensis, Gymnocypris waddellii, Gymnocypris dobula, and GE populations in clade A should be given priority for protection, the GE population in clade B should be given priority, and the GPR population in clade C should be given priority. In conclusion, the two models and assessment of conservation priorities will provide a scientific basis for the conservation of Gymnocypris species.

Regulating and controlling the stepwise ESDPT channel of BP(OH)2DCEt2 using the strategy of solvent polarity and external electric field.

Excited state double proton transfer (ESDPT) has attracted great scientific interest because of its excellent luminescent properties. However, the complex process of ESDPT has plagued theoretical and experimental scientists for a long time and has become a hot issue. In this work, the ESDPT process of 2,2'-bipyridine-3,3'-diol-5,5'-dicarboxylic acid ethyl ester (BP(OH)2DCEt2) is systematically studied and the regulation of the ESDPT process is further realized. The potential energy curves indicate that BP(OH)2DCEt2 shows the characteristics of stepwise ESDPT in different polar solvents. The increase in solvent polarity will be beneficial to the stepwise ESDPT reaction. Regrettably, it is not possible to distinguish the specific stepwise transfer path of the BP(OH)2DCEt2 molecule due to the symmetry of the potential energy surface along the diagonal. On this basis, we proposed a method to control and regulate the stepwise ESDPT path using an external electric field. The results show that the increase of external electric field intensity is favorable to stepwise ESDPT. It is interesting to note that applying an external electric field in a specific direction will effectively distinguish stepwise ESDPT reaction paths. Therefore, this work not only helps to understand the mechanism of ESDPT, but also contributes to regulation and design of new luminescent materials with excellent luminescent properties.

PAD4 controls tumor immunity via restraining the MHC class II machinery in macrophages.

Tumor-associated macrophages (TAMs) shape tumor immunity and therapeutic efficacy. However, it is poorly understood whether and how post-translational modifications (PTMs) intrinsically affect the phenotype and function of TAMs. Here, we reveal that peptidylarginine deiminase 4 (PAD4) exhibits the highest expression among common PTM enzymes in TAMs and negatively correlates with the clinical response to immune checkpoint blockade. Genetic and pharmacological inhibition of PAD4 in macrophages prevents tumor progression in tumor-bearing mouse models, accompanied by an increase in macrophage major histocompatibility complex (MHC) class II expression and T cell effector function. Mechanistically, PAD4 citrullinates STAT1 at arginine 121, thereby promoting the interaction between STAT1 and protein inhibitor of activated STAT1 (PIAS1), and the loss of PAD4 abolishes this interaction, ablating the inhibitory role of PIAS1 in the expression of MHC class II machinery in macrophages and enhancing T cell activation. Thus, the PAD4-STAT1-PIAS1 axis is an immune restriction mechanism in macrophages and may serve as a cancer immunotherapy target.

Development and evaluation of a time-resolved fluorescence labelled immunochromatographic strip assay for rapid and quantitative detection of bovine herpesvirus 1.

Bovine herpes virus 1 (BoHV-1) causes a wide variety of diseases in wild and domestic cattle. The most widely used method for viral identification is real-time PCR, which can only be performed in laboratories using sophisticated instruments by expert personnel. Herein, we developed an ultrasensitive time-resolved fluorescence lateral flow immunochromatographic strip (ICS) assay for detecting BoHV-1 in bovine samples using a monoclonal antibody against BoHV-1 labelled with fluorescent microspheres, which can be applied in any setting. The intact process from sample collection to final result can be achieved in 15 min. The limit of detection of the assay for BoHV-1 was 102 TCID50/100 µL. The coincidence rate of the ICS method and real-time PCR recommended by the World Organization for Animal Health (WOAH) was 100% for negative, 92.30% for positive, and 95.42% for total, as evaluated by the detection of 131 clinical samples. This detection method was specifically targeted to BoHV-1, not exhibiting cross-reactivity with other bovine pathogens including BoHV-5. We developed an ICS assay equipped with a portable instrument that offers a sensitive and specific platform for the rapid and reliable detection of BoHV-1 in the field. The Point-of-Care test of BoHV-1 is suitable for the screening and surveillance of BoHV-1 in dairy herds.

Use of 3D printing models for donor tooth extraction in autotransplantation cases.

OBJECTIVE: To clarify whether the 3D printing model has auxiliary functions in toto extraction of donor tooth in autotransplantation cases. METHODS: Two hundred and sixty patients who would have operation of ATT were divided into two groups. In group 1, determination of the tooth extraction in toto was predicted only according to the clinical and imaging examination. In group 2, the prediction was performed according to the clinical and imaging examination as well as the 3D model of donor tooth pre-extraction. A prespctive clinical study was designed on intra-group comparison between the predicted and actual donor teeth situation when extraction in cases of ATT. The consistent rate for the predicted results and the actual results were compared with the two groups. RESULTS: A remarkable difference was observed between the predicted results and the actual results of tooth positions and root numbers in group without model (p < 0,05). The consistency rate of the model group (94.62%) was significantly higher than that of non 3D model group (86.15%) (p = 0.034). CONCLUSION: The 3D printing model for the donor tooth is helpful for dentists to predict the accuracy of toto extraction of donor teeth in autotransplantation cases.

Effects of substitution and conjugation on photophysical properties of ESIPT-based fluorophores with the core of 4-aminophthalimide.

4-Aminophthalimide is a highly fluorescent signaling unit with excellent photophysical properties and wide application foregrounds. Based on this, a range of theoretical investigations are conducted on the fluorescent probe (E)-5-((2-hydroxybenzylidene) amino) isoindoline-1, 3-dione (HID) with the core of 4-aminophthalimide using density functional theory (DFT) and time-containing density functional theory (TD-DFT) methods in this paper. The optimized configurations, vertical excitation and emission energies, electronic characteristics and excited-state intramolecular proton transfer (ESIPT) behaviors of the probe HID are discussed in detail. Furthermore, to enhance the luminescent properties of HID, five novel compounds have been designed based on the structure of HID by introducing amino, methoxy and naphthalene groups (-NH2, -OMe and C10H8). Our work thoroughly explores how the property and position of substituents and conjugation affect photophysical characteristics and ESIPT processes. We find that the ESIPT dynamics can be modulated by the substitution and conjugation effects. Specifically, the introduction of amino and methoxy groups at the ortho-position and the introduction of the naphthalene group promote the ESIPT behavior of HID1, whereas the introduction of amino and methoxy groups at the meta-position exhibits the contrary impact. Therefore, we boldly infer that the introduction of electron-donating groups in the ortho-position and the introduction of the conjugated group make the ESIPT process more effortless to occur, whereas the introduction of substituents with opposing natures in the meta-position makes the ESIPT process more difficult to occur. In addition, the ionization potentials (IP), electron affinities (EA) and reorganization energies (λh and λe) of molecules are calculated to assess their potential as luminescent materials. Our work not only reveals the luminescence and ESIPT mechanism of the probe HID1, but also proposes to modulate the ESIPT process through the substitution and conjugation effects. In particular, the designed molecules have better photoelectric properties as a result of their red-shifted absorption and fluorescence spectra, smaller energy gaps, larger transferred charges and greater charge transferred distances, which offers some valuable ideas for the experimental development of more efficient organic luminescent materials with ESIPT properties.

DDX5 inhibits inflammation by modulating m6A levels of TLR2/4 transcripts during bacterial infection.

DExD/H-box helicases are crucial regulators of RNA metabolism and antiviral innate immune responses; however, their role in bacteria-induced inflammation remains unclear. Here, we report that DDX5 interacts with METTL3 and METTL14 to form an m6A writing complex, which adds N6-methyladenosine to transcripts of toll-like receptor (TLR) 2 and TLR4, promoting their decay via YTHDF2-mediated RNA degradation, resulting in reduced expression of TLR2/4. Upon bacterial infection, DDX5 is recruited to Hrd1 at the endoplasmic reticulum in an MyD88-dependent manner and is degraded by the ubiquitin-proteasome pathway. This process disrupts the DDX5 m6A writing complex and halts m6A modification as well as degradation of TLR2/4 mRNAs, thereby promoting the expression of TLR2 and TLR4 and downstream NF-κB activation. The role of DDX5 in regulating inflammation is also validated in vivo, as DDX5- and METTL3-KO mice exhibit enhanced expression of inflammatory cytokines. Our findings show that DDX5 acts as a molecular switch to regulate inflammation during bacterial infection and shed light on mechanisms of quiescent inflammation during homeostasis.

A cytosine analogue 5-azacitidine improves the accumulation of licochalcone A in licorice Glycyrrhiza inflata.

Licochalcone A (LCA) is a characteristic compound of Glycyrrhiza inflata with anti-inflammatory, antioxidant and antitumor activities. However, G. inflata produces LCA in low quantities that does not meet the market demand. In this study, we found that DNA methylation inhibitor 5-azacitidine (5-azaC) successfully improved the LCA contents in G. inflata seedlings. Transcriptome analysis revealed a series of differentially expressed genes (DEGs), including transcription factors such as MYB, ERF, WRKY, and some structural genes related to flavonoid biosynthesis. However, whole genome bisulfite sequencing (BS-seq) results showed little effect of the 5-azaC treatment on the alteration of DNA methylation on these genes, indicating the possibility that 5-azaC acts as a stimulus, but not an epigenetic modulation factor to improve the LCA content in G. inflata. Additionally, we applied the 5-azaC treatment to field plants and hairy roots and successfully increased the LCA contents in both cases. This research demonstrates the feasibility of 5-azaC treatments in future applications to improve plant production of LCA.

Identification and structural analysis of dimeric chicken complement component 3d and its binding with chicken complement receptor 2.

Complement component 3d (C3d), the final cleavage product of complement component C3, interacts with CR2 and thus plays a crucial role in linking the innate and adaptive immune systems. Additionally, human C3d executes various functions in its dimeric form, which is more effective than its monomeric form. In this study, we aimed to explored whether chicken C3d (chC3d) exhibits similar characteristics, namely dimerization and binding of dimeric chC3d to chicken CR2 (chCR2). We investigated the interaction and co-localization of chC3d with itself using coimmunoprecipitation and confocal laser scanning microscopy, respectively. Then, dimeric chC3d was detected using native polyacrylamide gel electrophoresis and western blotting, and its equilibrium dissociation constant KD (827 nM) was determined using surface plasmon resonance. Finally, the interaction modes of dimeric chC3d were identified using molecular docking simulations, which revealed that dimeric chC3d could crosslink with chCR2 receptor. Overall, our findings will facilitate future explorations of the chicken complement system.