Mechanochemical Fabrication of Full-Color Luminescent Materials from Aggregation-Induced Emission Prefluorophores for Information Storage and Encryption.

The development of luminescent materials via mechanochemistry embodies a compelling yet intricate frontier within materials science. Herein, we delineate a methodology for the synthesis of brightly luminescent polymers, achieved by the mechanochemical coupling of aggregation-induced emission (AIE) prefluorophores with generic polymers. An array of AIE moieties tethered to the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radical are synthesized as prefluorophores, which initially exhibit weak fluorescence due to intramolecular quenching. Remarkably, the mechanical coupling of these prefluorophores with macromolecular radicals, engendered through ball milling of generic polymers, leads to substantial augmentation of fluorescence within the resultant polymers. We meticulously evaluate the tunable emission of the AIE-modified polymers, encompassing an extensive spectrum from the visible to the near-infrared region. This study elucidates the potential of such materials in stimuli-responsive systems with a focus on information storage and encryption displays. By circumventing the complexity inherent to the conventional synthesis of luminescent polymers, this approach contributes a paradigm to the field of AIE-based polymers with implications for advanced technological applications.

A Review of Microsphere Super-Resolution Imaging Techniques.

Conventional optical microscopes are only able to resolve objects down to a size of approximately 200 nm due to optical diffraction limits. The rapid development of nanotechnology has increased the demand for greater imaging resolution, with a need to break through those diffraction limits. Among super-resolution techniques, microsphere imaging has emerged as a strong contender, offering low cost, simple operation, and high resolution, especially in the fields of nanodevices, biomedicine, and semiconductors. However, this technology is still in its infancy, with an inadequate understanding of the underlying principles and the technology's limited field of view. This paper comprehensively summarizes the status of current research, the advantages and disadvantages of the basic principles and methods of microsphere imaging, the materials and preparation processes, microsphere manipulation methods, and applications. The paper also summarizes future development trends.

Equivalent carbon number-based targeted odd-chain fatty acyl lipidomics reveals triacylglycerol profiling in clinical colon cancer.

Odd-chain FAs (OCFAs) are present in very low level at nearly 1% of total FAs in human plasma, and thus, their functions were usually ignored. Recent epidemiological studies have shown that OCFAs are inversely associated with a variety of disease risks. However, the contribution of OCFAs incorporated into complex lipids remains elusive. Here, we developed a targeted odd-chain fatty acyl-containing lipidomics method based on equivalent carbon number and retention time prediction. The method displayed good reproducibility and robustness as shown by peak width at half height within 0.7 min and coefficient of variation under 20%. A total number of 776 lipid species with odd-chain fatty acyl residues could be detected in the ESI mode of reverse-phase LC-MS, of which 309 lipids were further validated using multiple reaction monitoring transitions. Using this method, we quantified odd-chain fatty acyl-containing lipidome in tissues from 12 colon cancer patients, revealing the remodeling of triacylglycerol. The dynamics of odd-chain fatty acyl lipids were further consolidated by the association with genomic and proteomic features of altered catabolism of branched-chain amino acids and triacylglycerol endogenous synthesis in colon cancer. This lipidomics approach will be applicable for screening of dysregulated odd-chain fatty acyl lipids, which enriches and improves the methods for diagnosis and prognosis evaluation of cancer using lipidomics.

Molecular Engineering of Colloidal Atoms.

Creation of architectures with exquisite hierarchies actuates the germination of revolutionized functions and applications across a wide range of fields. Hierarchical self-assembly of colloidal particles holds the promise for materialized realization of structural programing and customizing. This review outlines the general approaches to organize atom-like micro- and nanoparticles into prescribed colloidal analogs of molecules by exploiting diverse interparticle driving motifs involving confining templates, interactive surface ligands, and flexible shape/surface anisotropy. Furthermore, the self-regulated/adaptive co-assembly of simple unvarnished building blocks is discussed to inspire new designs of colloidal assembly strategies.

A semilocal machine-learning correction to density functional approximations.

Machine learning (ML) has demonstrated its potential usefulness for the development of density functional theory methods. In this work, we construct an ML model to correct the density functional approximations, which adopts semilocal descriptors of electron density and density derivative and is trained by accurate reference data of relative and absolute energies. The resulting ML-corrected functional is tested on a comprehensive dataset including various types of energetic properties. Particularly, the ML-corrected Becke's three parameters and the Lee-Yang-Parr correlation (B3LYP) functional achieves a substantial improvement over the original B3LYP on the prediction of total energies of atoms and molecules and atomization energies, and a marginal improvement on the prediction of ionization potentials, electron affinities, and bond dissociation energies; whereas, it preserves the same level of accuracy for isomerization energies and reaction barrier heights. The ML-corrected functional allows for fully self-consistent-field calculation with similar efficiency to the parent functional. This study highlights the progress of building an ML correction toward achieving a functional that performs uniformly better than B3LYP.

OIT3 mediates macrophage polarization and facilitates hepatocellular carcinoma progression.

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related mortality; however, effective immunotherapy strategies are limited because of the immunosuppressive tumor microenvironment. Macrophages are essential components of the HCC microenvironment and are related to poor prognosis. Here, we evaluated the attributes of paracancer tissues in tumor immunity and progression using public databases. Based on the abundance of immune cells estimated by CIBERSORT, we performed weighted gene co-expression network analysis and found a specific module associated with M2 macrophages. Through analyzing interaction networks using Cytoscape and public datasets, we identified oncoprotein-induced transcript 3 (OIT3) as a novel marker of M2 macrophages. Overexpression of OIT3 remodeled immune features and reprogrammed the metabolism of M2 macrophages. Moreover, compared with wildtype macrophages, OIT3-overexpressing macrophages further enhanced the migration and invasion of co-cultured cancer cells. Additionally, OIT3-overexpressing macrophages promoted tumorigenesis and cancer development in vivo. Taken together, the findings demonstrate that OIT3 is a novel biomarker of alternatively activated macrophages and facilitates HCC metastasis.

Improving Density Functional Prediction of Molecular Thermochemical Properties with a Machine-Learning-Corrected Generalized Gradient Approximation.

The past decade has seen an increasing interest in designing sophisticated density functional approximations (DFAs) by integrating the power of machine learning (ML) techniques. However, application of the ML-based DFAs is often confined to simple model systems. In this work, we construct an ML correction to the widely used Perdew-Burke-Ernzerhof (PBE) functional by establishing a semilocal mapping from the electron density and reduced gradient to the exchange-correlation energy density. The resulting ML-corrected PBE is immediately applicable to any real molecule and yields significantly improved heats of formation while preserving the accuracy for other thermochemical and kinetic properties. This work highlights the prospect of combining the power of data-driven ML methods with physics-inspired derivations for reaching the heaven of chemical accuracy.

Integrated LC-MS metabolomics with dual derivatization for quantification of FFAs in fecal samples of hepatocellular carcinoma patients.

FFAs display pleiotropic functions in human diseases. Short-chain FAs (SCFAs), medium-chain FAs, and long-chain FAs are derived from different origins, and precise quantification of these FFAs is critical for revealing their roles in biological processes. However, accessing stable isotope-labeled internal standards is difficult, and different chain lengths of FFAs challenge the chromatographic coverage. Here, we developed a metabolomics strategy to analyze FFAs based on isotope-free LC-MS-multiple reaction monitoring integrated with dual derivatization. Samples and dual derivatization internal standards were synthesized using 2-dimethylaminoethylamine or dansyl hydrazine as a "light" label and N,N-diethyl ethylene diamine or N,N-diethyldansulfonyl hydrazide as a "heavy" label under mild and efficient reaction conditions. General multiple reaction monitoring parameters were designed to analyze these FFAs. The limit of detection of SCFAs varied from 0.5 to 3 nM. Furthermore, we show that this approach exhibits good linearity (R2 = 0.99374-0.99929), there is no serious substrate interference, and no quench steps are required, confirming the feasibility and reliability of the method. Using this method, we successfully quantified 15 types of SCFAs in fecal samples from hepatocellular carcinoma patients and healthy individuals; among these, propionate, butyrate, isobutyrate, and 2-methylbutyrate were significantly decreased in the hepatocellular carcinoma group compared with the healthy control group. These results indicate that the integrated LC-MS metabolomics with isotope-free and dual derivatization is an efficient approach for quantifying FFAs, which may be useful for identifying lipid biomarkers of cancer.

Modulating Hydroxyl-Rich Interfaces on Nickel-Copper Double Hydroxide Nanotyres to Pre-activate Alkaline Ammonia Oxidation Reactivity.

The surface hydroxyl groups of Nix Cu1-x (OH)2 play a crucial role in governing their conversion efficiency into Nix Cu1-x Ox (OH)2-x during the electro-chemical pre-activation process, thus affecting the integral ammonia oxidation reaction (AOR) reactivity. Herein, the rational design of hierarchical porous NiCu double hydroxide nanotyres (NiCu DHTs) was reported for the first time by considering hydroxyl-rich interfaces to promote pre-activation efficiency and intrinsic structural superiority (i.e., annulus, porosity) to accelerate AOR kinetics. A systematic investigation of the structure-function relationship was conducted by manipulating a series of NiCu DHs with tunable intercalations and morphologies. Remarkably, the NiCu DHTs exhibit superior AOR activity (onset potential of 1.31 V with 7.52 mA cm-2 at 1.5 V) and high ammonia sensitivity (detection limit of 9 µm), manifesting one of the best non-noble metal AOR electrocatalysts and electro-analytical electrodetectors. This work deepens the understanding of the crucial role of surface hydroxyl groups on determining the catalytic performance in alkaline medium.

The SP1-12LOX axis promotes chemoresistance and metastasis of ovarian cancer.

BACKGROUND: Ovarian cancer is the most lethal gynecologic cancer. Chemoresistance, especially platinum-resistance, is closely related to metastasis of ovarian cancer, however, the molecular basis by which links chemoresistance and metastasis remains vague. Disordered arachidonic acid (AA) metabolism has been shown to play an important role in the advanced ovarian cancer. This study aimed to explore the underlying mechanism involving eicosanoid metabolism that controlling chemoresistance and metastasis of ovarian cancer. METHODS: Cisplatin (DDP)-resistant SKOV3 (SKOV3-R) cells were constantly induced. Ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was performed to determine the AA metabolism in SKOV3 and SKOV3-R cells. Half maximal inhibitory concentration (IC50) and percentage of cell viability were tested using cell counting kit 8 (CCK-8). Realtime quantitative PCR (qPCR) and immunohistochemistry (IHC) were used to evaluate indicated genes and proteins respectively. Bioinformatic analysis and chromatin immunoprecipitation (ChIP) were performed to predict and identify the co-transcription factor of interest genes. Tumor growth and metastasis in the liver were assessed with nude mice by subcutaneously injection of SKOV3-R cells. RESULTS: SKOV3-R cells expressed higher multidrug resistance-associated proteins (MRPs) MRP1 and MRP4. They showed enhanced metastatic ability and produced increased AA-derived eicosanoids. Mechanistically, MRPs, epithelial mesenchymal transition (EMT) markers Snail and Slug, as well as key enzymes involved in AA-metabolism including 12-lipoxygenase (12LOX) were transcribed by the mutual transcription factor SP1 which was consistently upregulated in SKOV3-R cells. Inhibition of SP1 or 12LOX sensitized SKOV3-R cells to DDP and impaired metastasis in vitro and in vivo. CONCLUSION: Our results reveal that SP1-12LOX axis signaling plays a key role in DDP-resistance and metastasis, which provide a new therapeutic target for ovarian cancer.

Atom-Ratio-Conducted Tailoring of PdAu Bimetallic Nanocrystals with Distinctive Shapes and Dimensions for Boosting the ORR Performance.

Systematically manipulating the shape, dimension, and surface structure of PdAu nanocrystals is an active subject because it offers a powerful means to regulate and investigate their structure-activity relationship. Meanwhile, it is still urgent to reduce the use of two-dimensional precious-metal-based nanomaterials. This work demonstrates that PdAu nanocrystals with a variety of shapes/dimensions, including 1D anisotropic nanowires, 2D porous nanosheets, and 3D penetrative nanoflowers, can be systematically synthesized by simply adjusting the atomic ratio or the reaction time in the same protocol. The resultant PdAu nanocrystals with distinctive shapes, but the same building blocks triumphantly avoid the effects of facet and surface properties; this represents an ideal platform for directly comparing the oxygen reduction reaction (ORR) activity. 2D porous PdAu nanosheets demonstrate superior ORR performance (Eonset = 1.040 V, E1/2 = 0.932 V) compared with other-dimension-based samples and commercial Pd black; this is attributed to the abundant surface atoms and omni-directional mass-transfer channels. This work not only paves the way for systematically measuring a series of distinctive PdAu nanocrystals as non-Pt electrocatalysts, but also sheds light on the study of structures/dimensions in tuning the catalytic properties of bimetallic nanocrystals.

MiR-214 regulates fracture healing through inhibiting Sox4 and its mechanism.

OBJECTIVE: To investigate the expression of micro ribonucleic acid (miR)-214 in the bone tissue and blood of patients with fragility fracture. METHODS: The expression of miR-214 was detected via quantitative reverse transcription-polymerase chain reaction. The effect of miR-214 on proliferation and apoptosis of osteoblasts were detected via methyl thiazolyl tetrazolium assay and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining. RESULTS: The expression of miR-214 in the bone tissue and blood of patients with fragility fracture significantly declined. miR-214 could promote the proliferation of osteoblasts and inhibited the apoptosis of osteoblasts. miR-214 is involved in fracture healing through inhibiting Sox4 and promoting phosphorylation of PI3K/AKT pathway. The expression of BSP in cells treated with miR-214 mimics was significantly increased to 2.5-fold (p=0.0168), while the expression of BSP in cells treated with miR-214 AMO was significantly decreased, reduced to 0.3 times (p=0.0397). The expression of BMP2 in cells treated with miR-214 mimics was significantly increased to 2.5-fold (p=0.003), while the expression of BMP2 was significantly decreased in cells treated with miR-214 AMO, reduced to 0.3 times (p=0.0002). miR-214 can regulate the expression of Sox2, PI3K and AKT proteins. CONCLUSION: MiR-214 regulates the proliferation, apoptosis, bone formation of osteoblasts and participate in the fracture healing process by inhibiting the expression of Sox4, which provided new ideas for clinical treatment of fracture healing.

The triptolide-induced apoptosis of osteoclast precursor by degradation of cIAP2 and treatment of rheumatoid arthritis of TNF-transgenic mice.

This study aims to discuss the effect of triptolide (TPL) on rheumatoid arthritis (RA) and the mechanism related to osteoclast precursor (OCP) and osteoclast (OC). TNF-transgenic RA mice were treated with different doses of TPL by gavage. After the administration was finished, the curative effects were evaluated and compared, and the OCP apoptosis rates, the OC number, and the OC differentiation ability in vitro were detected. Finally, splenocytes of wild-type mice were cultured in vitro and induced to differentiate into OCP, and the cell apoptosis rate, cIAP2, and apoptotic effectors expression level were detected after cIAP2 overexpression and TPL administration. After TPL administration, the RA symptoms in the TPL groups were all better, the apoptosis rate of OCP was higher, and the amount of OC in vitro were lower than that in the control group (all P < 0.05), and all of the changes in the high-dose group were more obvious than the low-dose group. In splenocytes cells cultured in vitro, cIAP2 overexpression could decrease the apoptosis rate of OCPs and increase the OC number, and TPL treatment could down-regulate the cIAP2 and promote OCP apoptosis and OC reduction. In conclusion, TPL could induce OCP apoptosis and inhibit OC formation to effectively treat RA by mediating cIAP2 degradation.

Correlation of Autophagosome Formation with Degradation and Endocytosis Arabidopsis Regulator of G-Protein Signaling (RGS1) through ATG8a.

Damaged or unwanted cellular proteins are degraded by either autophagy or the ubiquitin/proteasome pathway. In Arabidopsis thaliana, sensing of D-glucose is achieved by the heterotrimeric G protein complex and regulator of G-protein signaling 1 (AtRGS1). Here, we showed that starvation increases proteasome-independent AtRGS1 degradation, and it is correlated with increased autophagic flux. RGS1 promoted the production of autophagosomes and autophagic flux; RGS1-yellow fluorescent protein (YFP) was surrounded by vacuolar dye FM4-64 (red fluorescence). RGS1 and autophagosomes co-localized in the root cells of Arabidopsis and BY-2 cells. We demonstrated that the autophagosome marker ATG8a interacts with AtRGS1 and its shorter form with truncation of the seven transmembrane and RGS1 domains in planta. Altogether, our data indicated the correlation of autophagosome formation with degradation and endocytosis of AtRGS1 through ATG8a.

Improving the Performance of Long-Range-Corrected Exchange-Correlation Functional with an Embedded Neural Network.

A machine-learning-based exchange-correlation functional is proposed for general-purpose density functional theory calculations. It is built upon the long-range-corrected Becke-Lee-Yang-Parr (LC-BLYP) functional, along with an embedded neural network which determines the value of the range-separation parameter µ for every individual system. The structure and the weights of the neural network are optimized with a reference data set containing 368 highly accurate thermochemical and kinetic energies. The newly developed functional (LC-BLYP-NN) achieves a balanced performance for a variety of energetic properties investigated. It largely improves the accuracy of atomization energies and heats of formation on which the original LC-BLYP with a fixed µ performs rather poorly. Meanwhile, it yields a similar or slightly compromised accuracy for ionization potentials, electron affinities, and reaction barriers, for which the original LC-BLYP works reasonably well. This work clearly highlights the potential usefulness of machine-learning techniques for improving density functional calculations.

Superparamagnetic iron oxide labeling limits the efficacy of rabbit immature dendritic cell vaccination by decreasing their antigen uptake ability in a lysosome-dependent manner.

Immature dendritic cells (iDCs) are for cell transplantation; however, no method has yet been developed for in vivo monitoring the transplanted iDCs. We have explored the feasibility of using superparamagnetic iron oxide (SPIO) labeling and magnetic resonance imaging for in vivo tracking of transplanted iDCs and determined the effects of SPIO labeling on iDC vaccination. With up to 50 µg Fe/ml, SPIO effectively labeled the iDCs without affecting their growth. At or above 100 µg Fe/ml, SPIO caused considerable damage to iDCs. SPIO labeling resulted in autophagosome formation and decreased the uptake of oxidized low density lipoprotein (ox-LDL), an exogenous antigen, by iDCs. SPIO and ox-LDL both localized to the lysosomes, and this competition for lysosomes could be partially responsible for the decreased ox-LDL phagocytic capacity of iDCs due to SPIO labeling.

Enhanced catalytic activity of Fe3O4-carbon dots complex in the Fenton reaction for enhanced immunotherapeutic and oxygenation effects.

Tumor metastasis and recurrence are closely related to immune escape and hypoxia. Chemodynamic therapy (CDT), photodynamic therapy (PDT), and photothermal therapy (PTT) can induce immunogenic cell death (ICD), and their combination with immune checkpoint agents is a promising therapeutic strategy. Iron based nanomaterials have received more and more attention, but their low Fenton reaction efficiency has hindered their clinical application. In this study, Fe3O4-carbon dots complex (Fe3O4-CDs) was synthesized, which was modified with ferrocenedicarboxylic acid by amide bond, and crosslinked into Fe3O4-CDs@Fc nano complex. The CDs catalyzed the Fenton reaction activity of Fe3O4 by helping to improve the electron transfer efficiency, extended the reaction pH condition to 7.4. The Fe3O4-CDs@Fc exhibit exceptional optical activity, achieving a thermal conversion efficiency of 56.43 % under 808 nm light and a photosensitive single-line state oxygen quantum yield of 33 % under 660 nm light. Fe3O4-CDs@Fc improved intracellular oxygen level and inhibited hypoxia-inducing factor (HIF-1α) by in-situ oxygen production based on Fenton reaction. The multimodal combination of Fe3O4-CDs@Fc (CDT/PDT/PTT) strongly induced immune cell death (ICD). The expression of immune-related protein and HIF-1α was investigated by immunofluorescence method. In vivo, Fe3O4-CDs@Fc combined with immune checkpoint blocker (antibody PD-L1, αPD-L1) effectively ablated primary tumors and inhibited distal tumor growth. Fe3O4-CDs@Fc is a promising immune-antitumor drug.

Immunoantitumor Activity and Oxygenation Effect Based on Iron-Copper-Doped Folic Acid Carbon Dots.

Cancer metastasis and recurrence are closely associated with immunosuppression and a hypoxic tumor microenvironment. Chemodynamic therapy (CDT) and photothermodynamic therapy (PTT) have been shown to induce immunogenic cell death (ICD), effectively inhibiting cancer metastasis and recurrence when combined with immune adjuvants. However, the limited efficacy of Fenton's reaction and suboptimal photothermal effect present significant challenges for successfully inducing ICD through CDT and PTT. This paper described the synthesis and immunoantitumor activity of the novel iron-copper-doped folic acid carbon dots (CFCFB). Copper-doped folic acid carbon dots (Cu-FACDs) were initially synthesized via a hydrothermal method, using folic acid and copper gluconate as precursors. Subsequently, the nanoparticles CFCFB were obtained through cross-linking and self-assembly of Cu-FACDs with ferrocene dicarboxylic acid (FeDA) and 3-bromopyruvic acid (3BP). The catalytic effect of carbon dots in CFCFB enhanced the activity of the Fenton reaction, thereby promoting CDT-induced ICD and increasing the intracellular oxygen concentration. Additionally, 3BP inhibited cellular respiration, further amplifying the oxygen concentration. The photothermal conversion efficiency of CFCFB reached 55.8%, which significantly enhanced its antitumor efficacy through photothermal therapy. Immunofluorescence assay revealed that treatment with CFCFB led to an increased expression of ICD markers, including calreticulin (CRT) and ATP, as well as extracellular release of HMGB-1, indicating the induction of ICD by CFCFB. Moreover, the observed downregulation of ARG1 expression indicates a transition in the tumor microenvironment from an immunosuppressive state to an antitumor state following treatment with CFCFB. The upregulation of IL-2 and CD8 expression facilitated the differentiation of effector T cells, resulting in an augmented population of CD8+ T cells, thereby indicating the activation of systemic immune response.

Stromal interaction molecule 1/microtubule-associated protein 1A/1B-light chain 3B complex induces metastasis of hepatocellular carcinoma by promoting autophagy.

Metastasis is the leading cause of death in hepatocellular carcinoma (HCC) patients, and autophagy plays a crucial role in this process by orchestrating epithelial-mesenchymal transition (EMT). Stromal interaction molecule 1 (STIM1), a central regulator of store-operated calcium entry (SOCE) in nonexcitable cells, is involved in the development and spread of HCC. However, the impact of STIM1 on autophagy regulation during HCC metastasis remains unclear. Here, we demonstrate that STIM1 is temporally regulated during autophagy-induced EMT in HCC cells, and knocking out (KO) STIM1 significantly reduces both autophagy and EMT. Interestingly, STIM1 enhances autophagy through both SOCE-dependent and independent pathways. Mechanistically, STIM1 directly interacts with microtubule-associated protein 1A/1B-light chain 3B (LC3B) to form a complex via the sterile-α motif (SAM) domain, which promotes autophagosome formation. Furthermore, deletion of the SAM domain of STIM1 abolishes its binding with LC3B, leading to a decrease in autophagy and EMT in HCC cells. These findings unveil a novel mechanism by which the STIM1/LC3B complex mediates autophagy and EMT in HCC cells, highlighting a potential target for preventing HCC metastasis.