Alpha-kinase 1 (ALPK1) agonist DF-006 demonstrates potent efficacy in mouse and primary human hepatocyte (PHH) models of hepatitis B.

BACKGROUND AND AIMS: In the treatment of chronic hepatitis B (CHB) infection, stimulation of innate immunity may lead to hepatitis B virus (HBV) cure. Alpha-kinase 1 (ALPK1) is a pattern recognition receptor (PRR) that activates the NF-κB pathway and stimulates innate immunity. Here we characterized the preclinical anti-HBV efficacy of DF-006, an orally active agonist of ALPK1 currently in clinical development for CHB. APPROACH AND RESULTS: In adeno-associated virus (AAV)-HBV mouse models and primary human hepatocytes (PHHs) infected with HBV, we evaluated the antiviral efficacy of DF-006. In the mouse models, DF-006 rapidly reduced serum HBV DNA, hepatitis B surface antigen, and hepatitis B e antigen levels using doses as low as 0.08 µg/kg, 1 µg/kg, and 5 µg/kg, respectively. DF-006 in combination with the HBV nucleoside reverse transcriptase inhibitor, entecavir, further reduced HBV DNA. Antiviral efficacy in mice was associated with an increase in immune cell infiltration and decrease of hepatitis B core antigen, encapsidated pregenomic RNA, and covalently closed circular DNA in liver. At subnanomolar concentrations, DF-006 also showed anti-HBV efficacy in PHH with significant reductions of HBV DNA. Following dosing with DF-006, there was upregulation of NF-κB-targeted genes that are involved in innate immunity. CONCLUSION: DF-006 was efficacious in mouse and PHH models of HBV without any indications of overt toxicity. In mice, DF-006 localized primarily to the liver where it potently activated innate immunity. The transcriptional response in mouse liver provides insights into mechanisms that mediate anti-HBV efficacy by DF-006.

Theoretical Study on the Mechanism of Ru(II)-Catalyzed Intermolecular [3 + 2] Annulation between o-Toluic Acid and 3,5-Bis(trifluoromethyl)benzaldehyde: Octahedral vs Trigonal Bipyramidal.

Density functional theory was utilized to investigate the mechanism of Ru(II)-catalyzed aromatic C-H activation and addition of aromatic aldehydes. The proposed catalytic cycle consists of C-H bond activation, aldehyde carbonyl insertion for C-C coupling, lactonization for the formation of the final product, product separation, and catalyst recovery. Our calculations suggest that Ru(OAc)2(PCy3) (referred to as CAT) is the most favorable active catalyst, facilitating the C-H bond activation to form a five-membered ring cycloruthenium intermediate (INT2). Subsequently, the aromatic aldehyde reactant 2a enters the Ru coordination sphere, accelerating the C-C coupling and lactonization for the formation of the final product. The involvement of acetate assists in the final product separation, while INT1 re-enters the Ru coordination sphere to initiate a new catalytic cycle. Utilizing the energetic span model, the apparent activation free energy barrier was computed to be 34.3 kcal mol-1 at 443 K. Furthermore, exploration of the reaction mechanism in the absence of phosphine ligands identified Ru(OAc)2(p-cymene) as the most favorable active catalyst. The derived apparent activation free energy barrier offers a comprehensive explanation for the experimentally observed yields. Additionally, we have examined the disparities between the octahedral and trigonal bipyramidal structures of the catalysts concerning their effects on the reaction mechanisms and apparent activation free energy barriers.

High energy barrier hydroxyl radical dissociation mechanism of a low shock sensitivity dihydroxylammonium 5,5'-bistetrazole-1,1'-diolate (TKX-50) explosive.

As a representative of the new generation of high-energy explosives, TKX-50 has attracted widespread attention due to its remarkably low sensitivity toward shock. However, the reported decomposition barriers of TKX-50 (∼37 kcal mol-1) are comparable to those of commonly used explosives. The mechanism of its low shock sensitivity remains unclear. In this study, using an ab initio molecular dynamics method combined with a multiscale shock simulation technique and transition state calculations (at the B2PLYP-D3/Def2TZVP level), we discovered an unconventional reaction pathway of TKX-50 under shock, and its rate-controlling step is the dissociation of the hydroxyl radical (OH) from the anion ring after proton transfer, followed by ring rupture and the production of H2O and N2. The barrier for this OH dissociation reaction is as high as 51.9 kcal mol-1. In contrast, under thermal stimuli, TKX-50 prefers to open rings directly after proton transfer without losing the OH. The corresponding barrier is 35.4 kcal mol-1, which is in good agreement with previous studies. The reason for the unconventional reaction pathway of TKX-50 under shock may be the suppression of anion ring opening in thermal decomposition by steric hindrance upon shock compression. In addition, the dominant N2 generation pathway under shock releases less energy than pyrolysis which further explains the low shock sensitivity of TKX-50. This study comprehensively elucidates the different reaction mechanisms of TKX-50 under thermal and shock conditions and proposes a crucial reaction pathway leading to its low shock sensitivity. These findings will contribute to the understanding and application of tetrazole anionic energetic salts.

Effects and mechanisms of substance P on the proliferation and angiogenic differentiation of bone marrow mesenchymal stem cells: Bioinformatics and in vitro experiments.

The slight release of substance P (SP) from the end of peripheral nerve fibers causes a neurogenic inflammatory reaction, promotes vascular dilation and increases vascular permeability. However, whether SP can promote the angiogenesis of bone marrow mesenchymal stem cells (BMSCs) under high glucose conditions has not been reported. This study analyzed the targets, biological processes and molecular mechanisms underlying the effects of SP on BMSCs. BMSCs cultured in vitro were divided into a normal control group, high glucose control group, high glucose SP group and high glucose Akt inhibitor group to verify the effects of SP on BMSCs proliferation, migration and angiogenic differentiation. SP was found to act on 28 targets of BMSCs and participate in angiogenesis. Thirty-six core proteins, including AKT1, APP, BRCA1, CREBBP and EGFR, were identified. In a high glucose environment, SP increased the BMSCs proliferation optical density value and cell migration number and reduced the BMSCs apoptosis rate. In addition, SP induced BMSCs to highly express the CD31 protein, maintain the wall structure integrity of the matrix glue mesh and promote increases in the number of matrix glue meshes. These experiments showed that in a high glucose environment, SP acts on 28 targets of BMSCs that encode core proteins, such as AKT1, APP and BRCA1, and improves BMSCs proliferation, migration and angiogenic differentiation through the Akt signaling pathway.

Reversible Local Protonation-Deprotonation: Tuning Stimuli-Responsive Circularly Polarized Luminescence in Chiral Hybrid Zinc Halides for Anti-Counterfeiting and Encryption.

Precise control over the organic composition is crucial for tailoring the distinctive structures and properties of hybrid metal halides. However, this approach is seldom utilized to develop materials that exhibit stimuli-responsive circularly polarized luminescence (CPL). Herein, we present the synthesis and characterization of enantiomeric hybrid zinc bromides: biprotonated ((R/S)-C12H16N2)ZnBr4 ((R/S-LH2)ZnBr4) and monoprotonated ((R/S)-C12H15N2)2ZnBr4 ((R/S-LH1)2ZnBr4), derived from the chiral organic amine (R/S)-2,3,4,9-Tetrahydro-1H-carbazol-3-amine ((R/S)-C12H14N2). These compounds showcase luminescent properties; the zero-dimensional biprotonated form emits green light at 505 nm, while the monoprotonated form, with a pseudo-layered structure, displays red luminescence at 599 and 649 nm. Remarkably, the reversible local protonation-deprotonation behavior of the organic cations allows for exposure to polar solvents and heating to induce reversible structural and luminescent transformations between the two forms. Theoretical calculations reveal that the lower energy barrier associated with the deprotonation process within the pyrrole ring is responsible for the local protonation-deprotonation behavior observed. These enantiomorphic hybrid zinc bromides also exhibit switchable circular dichroism (CD) and CPL properties. Furthermore, their chloride counterparts were successfully obtained by adjusting the halogen ions. Importantly, the unique stimuli-responsive CPL characteristics position these hybrid zinc halides as promising candidates for applications information storage, anti-counterfeiting, and information encryption.

Design, Synthesis, and Biological Evaluation of New Urushiol Derivatives as Potent Class I Histone Deacetylase Inhibitors.

In the present study, a novel series of 11 urushiol-based hydroxamic acid histone deacetylase (HDAC) inhibitors was designed, synthesized, and biologically evaluated. Compounds 1-11 exhibited good to excellent inhibitory activities against HDAC1/2/3 (IC50 : 42.09-240.17 nM) and HDAC8 (IC50 : 16.11-41.15 nM) in vitro, with negligible activity against HDAC6 (>1409.59 nM). Considering HDAC8, docking experiments revealed some important features contributing to inhibitory activity. According to Western blot analysis, select compounds could notably enhance the acetylation of histone H3 and SMC3 but not-tubulin, indicating their privileged structure is appropriate for targeting class I HDACs. Furthermore, antiproliferation assays revealed that six compounds exerted greater in vitro antiproliferative activity against four human cancer cell lines (A2780, HT-29, MDA-MB-231, and HepG2, with IC50 values ranging from 2.31-5.13 µM) than suberoylanilide hydroxamic acid; administration of these compounds induced marked apoptosis in MDA-MB-231 cells, with cell cycle arrest in the G2/M phase. Collectively, specific synthesized compounds could be further optimized and biologically explored as antitumor agents.

Diverse intratumoral heterogeneity and immune microenvironment of two HPV-related cervical cancer types revealed by single-cell RNA sequencing.

Cervical squamous cell carcinoma (SCC) and adenocarcinoma (AD) are the main histological types of human papillomavirus-related cervical cancer. However, there are few reports on cell type-specific molecular differences between SCC and AD. Here, we used unbiased droplet-based single-cell RNA sequencing to elucidate the cellular differences between SCC and AD in tumor heterogeneity, and tumor microenvironment (TME). A total of 61 723 cells from three SCC and three AD patients, were collected and divided into nine cell types. Epithelial cells exhibited high intra- and interpatient heterogeneity and functional diversity. Signaling pathways, such as epithelial-to-mesenchymal-transition (EMT), hypoxia and inflammatory response were upregulated in SCC, while cell cycle-related signaling pathways were highly enriched in AD. SCC was associated with high infiltration of cytotoxicity CD8 T, effector memory CD8 T, proliferative natural killer (NK), and CD160+ NK cells as well as tumor-associated macrophages (TAMs) with high major histocompatibility complex-II genes. AD exhibited a high proportion of naive CD8 T, naive CD4 T, Treg CD4, central memory CD8, and TAMs with immunomodulatory functions. Additionally, we also observed that the majority of cancer-associated fibroblasts (CAFs) were from AD, and participated in inflammation regulation, while SCC-derived CAFs exhibited similar functions to tumor cells, such as EMT and hypoxia. This study revealed the widespread reprogramming of multiple cell populations in SCC and AD, dissected the cellular heterogeneity and characteristics in TME, and proposed potential therapeutic strategies for CC, such as targeted therapy and immunotherapy.

The treatment of dispersion terms for solution systems.

DFT calculations of reaction mechanisms in solution have always been a hot topic, especially for transition-metal-catalyzed reactions, in which the traditional DFT-D3 method has been extensively employed. The overestimation of the dispersion from the traditional DFT-D3 method leads to a quite low activation free-energy barrier, so it is worth finding a proper way to deal with the dispersion for solution systems. The solvent-solute dispersion is also important for solution systems, and thus it should be calculated together with the solute dispersion. The newly generated solute-solute dispersion energy should be shared equally with the newly formed cavity between two interacting species; therefore, only half of the solute-solute and solvent-solute dispersion terms belong to the solute molecule. The detailed treatment of dispersion correction for solution systems has been fully addressed, and this method has been confirmed with the examples of ligand exchange reactions and catalytic reactions.

DFT calculations in solution systems: solvation energy, dispersion energy and entropy.

DFT calculations of reaction mechanisms in solution have always been a hot topic, especially for transition-metal-catalyzed reactions. The calculation of solvation energy is performed using either the polarizable continuum model (PCM) or the universal solvation model SMD. The PCM calculation is very sensitive to the choice of atomic radii to form a cavity, where the self-consistent isodensity PCM (SCI-PCM) has been recognized as the best choice and our IDSCRF radii can provide a similar cavity. Moving from a gas-phase case to a solution case, dispersion energy and entropy should be carefully treated. The solvent-solute dispersion is also important in solution systems, and it should be calculated together with the solute dispersion. Only half of the solvent-solute dispersion energy from the PCM calculation belongs to the solute molecules to maintain a thermal equilibrium between a solute molecule and its cavity, similar to the treatment of electrostatic energy. Relative solute dispersion energy should also be shared equally with the newly formed cavity. The entropy change from a gas phase to a liquid phase is quite large, but the modern quantum chemistry programs can only calculate the gas-phase translational entropy based on the idea-gas equation. In this review, we will provide an operable method to calculate the solution translational entropy, which has been coded in our THERMO program.

Machine learning quantitatively characterizes the deformation and destruction of explosive molecules.

Although explosives have been widely used in mines, road development, old building demolishing, and munition explosions; currently, how chemical bonds between atoms break and recombine, how the molecular structure is deformed and destroyed, how the reaction product molecules are formed, and the details for this rapid change process in explosive reactions are not yet fully understood, which limits the full use of explosive energy and safer use of explosives. This paper presents a quantitative model of molecular structure deformation using machine learning algorithms as well as a qualitative model of its relationship with molecular structure destruction, based on a molecular dynamics simulation and detailed analysis of the shock-loaded ε-CL-20, providing new perspectives for explosive community research. Specifically, the quantitative model of molecular structure deformation establishes the quantitative relationship between the molecular volume change and molecular position change, and between molecular distance change and molecular volume change using the machine learning algorithms such as Delaunay triangulation, clustering, and gradient descent. We find that the molecular spacing in explosives is strongly compressed after being shocked, and the peripheral structure can shrink inward, which is beneficial to keep the cage structure stable. When the peripheral structure is compressed to a certain extent, the cage structure volume begins to expand and is then destroyed. In addition, hydrogen atom transfer occurs within the explosive molecule. This study amplifies the structural changes and the chemical reaction process for explosive molecules after being strongly compressed by a shock wave, which can enrich the knowledge of the real detonation reaction process. The analysis method based on quantitative characterization using machine learning proposed in this study can also be used to analyze the microscopic reaction mechanism in other materials.

625 nm Light Irradiation Prevented MC3T3-E1 Cells from Accumulation of Misfolded Proteins via ROS and ATP Production.

Osteoblasts must acquire a considerable capacity for folding unfolded and misfolded proteins (MPs) to produce large amounts of extracellular matrix proteins and maintain bone homeostasis. MP accumulation contributes to cellular apoptosis and bone disorders. Photobiomodulation therapy has been used to treat bone diseases, but the effects of decreasing MPs with photobiomodulation remain unclear. In this study, we explored the efficacy of 625 nm light-emitting diode irradiation (LEDI) to reduce MPs in tunicamycin (TM) induced-MC3T3-E1 cells. Binding immunoglobulin protein (BiP), an adenosine triphosphate (ATP)-dependent chaperone, is used to evaluate the capacity of folding MPs. The results revealed that pretreatment with 625 nm LEDI (Pre-IR) induced reactive oxygen species (ROS) production, leading to the increased chaperone BiP through the inositol-requiring enzyme 1 (IRE1)/X-box binding protein 1s (XBP-1s) pathway, and then restoration of collagen type I (COL-I) and osteopontin (OPN) expression relieving cell apoptosis. Furthermore, the translocation of BiP into the endoplasmic reticulum (ER) lumen might be followed by a high level of ATP production. Taken together, these results suggest that Pre-IR could be beneficial to prevent MP accumulation through ROS and ATP in TM-induced MC3T3-E1cells.

Effects of Red LED Irradiation in Enhancing the Mineralization of Human Dental Pulp Cells In Vitro.

Dentin regeneration is the preferred method used to preserve dental pulp vitality after pulp exposure due to caries. Red light-emitting diode irradiation (LEDI), which is based on photobiomodulation (PBM), has been used to promote hard-tissue regeneration. However, the underlying mechanism still needs elucidation. This study aimed to explore the mechanism involved in red LEDI affecting dentin regeneration. Alizarin red S (ARS) staining revealed that red LEDI induced mineralization of human dental pulp cells (HDPCs) in vitro. We further distinguished the cell proliferation (0-6 d), differentiation (6-12 d), and mineralization (12-18 d) of HDPCs in vitro and treated cells either with or without red LEDI in each stage. The results showed that red LEDI treatment in the mineralization stage, but not the proliferation or differentiation stages, increased mineralized nodule formation around HDPCs. Western blot also indicated that red LEDI treatment in the mineralization stage, but not the proliferation or differentiation stages, upregulated the expression of dentin matrix marker proteins (dentin sialophosphoprotein, DSPP; dentin matrix protein 1, DMP1; osteopontin, OPN) and an intracellular secretory vesicle marker protein (lysosomal-associated membrane protein 1, LAMP1). Therefore, the red LEDI might enhance the matrix vesicle secretion of HDPCs. On the molecular level, red LEDI enhanced mineralization by activating the mitogen-activated protein kinase (MAPK) signaling pathways (ERK and P38). ERK and P38 inhibition reduced mineralized nodule formation and the expression of relevant marker proteins. In summary, red LEDI enhanced the mineralization of HDPCs by functioning to produce a positive effect in the mineralization stage in vitro.

Characterization and Comparison of Steroidal Glycosides from Polygonatum Species by High-Performance Liquid Chromatography-Electrospray Ionization Mass Spectrometry.

Polygonatum species have been used as traditional medicines and functional foods in Asia and Europe since ancient times. In this study, a fast and simple method based on liquid chromatography coupled with electrospray ionization mass spectrometry (LC-ESI-MS) was developed to systematically analyze and identify the steroidal glycosides in four major Polygonatum species distributed in Japan, including P. odoratum, P. falcatum, P. macranthum, and P. sibiricum. As a result, 31 steroidal glycosides were tentatively identified, including 18 known and 13 previously unreported glycosides. Their structures were identified by the interpretation of chromatographic behavior and ESI-MS fragmentation patterns. The identification of 31 steroidal glycosides was indicative of a common biogenetic pathway in Polygonatum species. Our study disclosed the chemical profiling of steroidal glycosides in the plants of Polygonatum species, which will benefit better phytochemotaxonomical and phytochemical understanding and quality control for their medicinal usage.

Comparative Study on the Sensing Kinetics of Carbon and Nitrogen Nutrients in Cancer Tissues and Normal Tissues Based Electrochemical Biosensors.

In this study, an electrochemical sensor was developed by immobilizing colon cancer and the adjacent tissues (peripheral healthy tissues on both sides of the tumor) and was used to investigate the receptor sensing kinetics of glucose, sodium glutamate, disodium inosinate, and sodium lactate. The results showed that the electrical signal triggered by the ligand-receptor interaction presented hyperbolic kinetic characteristics similar to the interaction of an enzyme with its substrate. The results indicated that the activation constant values of the colon cancer tissue and adjacent tissues differed by two orders of magnitude for glucose and sodium glutamate and around one order of magnitude for disodium inosinate. The cancer tissues did not sense sodium lactate, whereas the adjacent tissues could sense sodium lactate. Compared with normal cells, cancer cells have significantly improved nutritional sensing ability, and the improvement of cancer cells' sensing ability mainly depends on the cascade amplification of intracellular signals. However, unlike tumor-adjacent tissues, colon cancer cells lose the ability to sense lactate. This provides key evidence for the Warburg effect of cancer cells. The methods and results in this study are expected to provide a new way for cancer research, treatment, the screening of anticancer drugs, and clinical diagnoses.

Study of the Sensing Kinetics of G Protein-Coupled Estrogen Receptor Sensors for Common Estrogens and Estrogen Analogs.

Endogenous and exogenous estrogens are widely present in food and food packaging, and high levels of natural estrogens and the misuse or illegal use of synthetic estrogens can lead to endocrine disorders and even cancer in humans. Therefore, it is consequently important to accurately evaluate the presence of food-functional ingredients or toxins with estrogen-like effects. In this study, an electrochemical sensor based on G protein-coupled estrogen receptors (GPERs) was fabricated by self-assembly, modified by double-layered gold nanoparticles, and used to measure the sensing kinetics for five GPER ligands. The interconnected allosteric constants (Ka) of the sensor for 17ß-estradiol, resveratrol, G-1, G-15, and bisphenol A were 8.90 × 10-17, 8.35 × 10-16, 8.00 × 10-15, 5.01 × 10-15, and 6.65 × 10-16 mol/L, respectively. The sensitivity of the sensor for the five ligands followed the order of 17ß-estradiol > bisphenol A > resveratrol > G-15 > G-1. The receptor sensor also demonstrated higher sensor sensitivity for natural estrogens than exogenous estrogens. The results of molecular simulation docking showed that the residues Arg, Glu, His, and Asn of GPER mainly formed hydrogen bonds with -OH, C-O-C, or -NH-. In this study, simulating the intracellular receptor signaling cascade with an electrochemical signal amplification system enabled us to directly measure GPER-ligand interactions and explore the kinetics after the self-assembly of GPERs on a biosensor. This study also provides a novel platform for the accurate functional evaluation of food-functional components and toxins.

Multiple Stimuli-Responsive Luminescent Chiral Hybrid Antimony Chlorides for Anti-Counterfeiting and Encryption Applications.

Stimuli-responsive circularly polarized luminescence (CPL) materials are ideal for information anti-countering applications, but the best-performing materials have not yet been identified. This work presents enantiomorphic hybrid antimony halides R-(C5 H12 NO)2 SbCl5 (1) and S-(C5 H12 NO)2 SbCl5 (2) showing mirror-imaged CPL activity with a dissymmetry factor of 1.2×10-3 . Interestingly, the DMF-induced structural transformation is realized to obtain non-emissive R-(C5 H12 NO)2 SbCl5 ⋅ DMF (3) and S-(C5 H12 NO)2 SbCl5 ⋅ DMF (4) upon exposure to DMF vapor. The transformation process is reversed upon heating. DFT calculations showed that the DMF-induced-quenched-luminescence is attributed to the intersection of the ground and excited state curves on the configuration coordinates. Unexpectedly, the nanocrystals of the chiral antimony halides 1 and 2 were prepared and indicate the excellent solution process performance. The reversible PL and CPL switching gives the system applications in information technology, anti-counterfeiting, encryption-decryption, and logic gates.

Effects of Bacillus subtilis subsp. on the microbial community and aroma components of flue-cured tobacco leaves based on metagenome analysis.

To improve the sensory quality of aged flue-cured tobacco (FCT), Bacillus subtilis subsp, H11 was inoculated on aged FCT leaves named Pingdingshan DCFB. The metagenome and thecharacteristic aroma substances of aged FCT with different fermentation times (0 h, 12 h, 24 h, and 36 h) were systematically analyzed. The results showed that the content of aroma components and sensory quality of aged FCT were significantly improved when the strain was treated at 35 °C with 25% moisture for 24 h. The inoculation of H11 had a strong influence on the microbial composition and metabolism of the aged FCT leaf surface. Five microorganisms Pantoea (35.04%, 20.12-56.95%), Enterobacter (22.16, 13.60-39.82%), Pseudomonas (12.12, 3.13-26.17%), Terribacillus (8.00%, 4.65-13.01%) and Bacillus (6.54%, 0.67-16.96%) accounted for the largest proportion during the process of fermentation. The content of most neutral flavor components such as ketones and aldehydes in FCT after fermentation was higher than that priorto fermentation. After 24 h fermentation, 3-furfural, 5-methylfurfural, dihydrokiwi lactone and megalotrienone increased by 71.42%, 49.19%, 21.09%, and 10.56%, respectively. Correlation analysis between groups showed that Pseudomonas was significantly correlated with (E, E)-2, 4-heptadienal (P < 0.05), Franconibacter was correlated with damascus ketone (P < 0.05), and Terribacillus was related to the production of ß-citral (P < 0.05). GH9 may be involved in the formation of damasone (P < 0.05), and 4-cyclopentene-1, 3-dione was significantly correlated with glycoside hydrolase family 5 (GH5) (P < 0.05). The correlation between 4-oxyisophorone and GH31, GH103, GH73, and GH3 was significant (P < 0.05). Microorganisms and GHs may play important roles in FCT fermentation.

Simultaneous Spectral Tuning and Thermal Stability Adjustment in Ca8ZnGa(1-x)Lax(PO4)7:Eu2+ Phosphors.

The modifications of local structure in solid solution are a crucial step to regulate the photoluminescence properties of rare-earth ion-based phosphors. However, the structural diversity of host matrices and the uncertain occupation of activators make it challenging to obtain phosphors with both high stability and tailored emission. Herein, We synthesized a series of ß-Ca3(PO4)2-type Ca8ZnGa(1-x)Lax(PO4)7:Eu2+ solid solution phosphors by design. By modifying the Ga/La ratio, controllable regulation of the emission spectrum and thermal stability of the phosphors can be achieved at the same time. The introduction of La3+ can regulate the crystal field splitting strength of the Eu2+ activators, causing redshifts in the emission spectrum while increasing Ga3+ content will lead to enhanced energy transfer between the oxygen vacancy and Eu2+, as well as improved thermal stability. Through local structure modification, the spectrum and thermal stability of phosphors can be facilely tuned. The results indicate that this series of phosphors have versatile potentials in various applications.

Microfluidic Transport of Hybrid Optoplasmonic Particles for Repeatable SERS Detection.

For its ultrahigh sensitivity, the microfluidic system combined with surface-enhanced Raman spectroscopy (SERS) becomes one of the most interesting topics in integrated online monitoring related fields. In previous reports, the commonest surface plasmon-enhanced substrates in microfluidics consist of immobilized metal nanostructures on the channel surface to overcome the disturbance of Brownian motion. In this work, a hybrid optoplasmonic microfluidic conveyer is developed, in which the movable, highly ordered optoplasmonic particles are delivered to the detection spot for SERS detection. Here, the optoplasmonic particle is the SiO2 microsphere with in situ photochemical reduced Ag nanoparticles on the surface. Because of the converged light at the SiO2 microsphere surface, the SERS spectra collected at this optoplasmonic particle in the channel exhibit excellent performance, which is confirmed by the simulated electric field distribution. In addition, the experimental data also demonstrate that the quantitative analysis is achieved at 1 nM in this optoplasmonic microfluidic conveyer. Furthermore, the used optoplasmonic particle can be ejected from the microfluidic channel by modulating the velocity of injected fluid such that the new optoplasmonic particle will be delivered to the detection spot for repeatable SERS detection in the same channel. The dynamic process of optoplasmonic particle transport is investigated in this microconveyer, and the built theoretical model to predict the particle release is highly identical with the experimental data. These data point out that our hybrid optoplasmonic microfluidic conveyer has repeatable enhanced substrates with the high SERS sensitivity to overcome the cross-contamination of different target molecules in repeatable detection.

Microfluidic integrated capacitive biosensor for C-reactive protein label-free and real-time detection.

A microfluidic chip has been integrated with a capacitive biosensor based on mass-producible three-dimensional (3D) interdigital electrode arrays. To achieve the monitoring of biosensor preparation and cardiac- and periodontitis-related biomarkers, all the processes were detected in a continuously on-site way. Fabrication steps for the microfluidic chip-bonded 3D interdigital capacitor biosensor include gold thiol modification, the activation of EDC/sulfo-NHS, and the bioconjugation of antibodies. Fluorescent characterization and X-ray photoelectron spectroscopy analysis were applied to assess the successful immobilization of the C-reactive protein (CRP) antibody. The experimental results indicate the good specificity and high sensitivity of the microfluidic integrated 3D capacitive biosensor. The limit of detection of the 3D capacitive biosensor for CRP label-free detection was about 1 pg mL-1. This 3D capacitive biosensor with integrated microfluidics is mass-producible and has achieved the on-site continuous detection of cardiac- and periodontitis-related biomarkers with high performance.