Tuning Dynamic Structural Evolution of Bi24O31Cl10 for Enhancing Piezo-Photocatalytic Nitrogen Oxidation to Nitrate.

Direct nitrogen oxidation into nitrate under ambient conditions presents a promising strategy for harsh and multistep industrial processes. However, the dynamic structural evolution of active sites in surface reactions constitutes a highly intricate endeavor and remains in its nascent stage. Here, we constructed a Bi24O31Cl10 material with moiré superlattice structure (BCMS) for direct piezo-photocatalytic oxidation of nitrogen into nitrate. Excitingly, BCMS achieved excellent nitric acid production (15.44 mg g-1 h-1) under light and pressure conditions. Detailed experimental results show that the unique structure extracts the local strain tensor from the constricting Bi-Bi bond and Bi-O bond for internal structural reconstruction, which promotes the formation of electron and reactive molecule vortexes to facilitate charge transfer as well as N2 and O2 adsorption. Ultimately, these initiatives strengthen electron exchange between the superoxide radical and nitrogen as well as the binding strength of multiple intermediates, which swayingly adjusts the reaction path and energy barriers.

Genome-wide analysis of the U-box E3 ligases gene family in potato (Solanum tuberosum L.) and overexpress StPUB25 enhance drought tolerance in transgenic Arabidopsis.

BACKGROUND: Plant U-box (PUB) E3 ubiquitin ligases have vital effects on various biological processes. Therefore, a comprehensive and systematic identification of the members of the U-box gene family in potato will help to understand the evolution and function of U-box E3 ubiquitin ligases in plants. RESULTS: This work identified altogether 74 PUBs in the potato (StPUBs) and examined their gene structures, chromosomal distributions, and conserved motifs. There were seventy-four StPUB genes on ten chromosomes with diverse densities. As revealed by phylogenetic analysis on PUBs within potato, Arabidopsis, tomato (Solanum lycopersicum), cabbage (Brassica oleracea), rice (Oryza sativa), and corn (Zea mays), were clustered into eight subclasses (C1-C8). According to synteny analysis, there were 40 orthologous StPUB genes to Arabidopsis, 58 to tomato, 28 to cabbage, 7 to rice, and 8 to corn. In addition, RNA-seq data downloaded from PGSC were utilized to reveal StPUBs' abiotic stress responses and tissue-specific expression in the doubled-monoploid potato (DM). Inaddition, we performed RNA-seq on the 'Atlantic' (drought-sensitive cultivar, DS) and the 'Qingshu NO.9' (drought-tolerant cultivar, DT) in early flowering, full-blooming, along with flower-falling stages to detect genes that might be involved in response to drought stress. Finally, quantitative real-time PCR (qPCR) was carried out to analyze three candidate genes for their expression levels within 100 mM NaCl- and 10% PEG 6000 (w/v)-treated potato plantlets for a 24-h period. Furthermore, we analyzed the drought tolerance of StPUB25 transgenic plants and found that overexpression of StPUB25 significantly increased peroxidase (POD) activity, reduced ROS (reactive oxygen species) and MDA (malondialdehyde) accumulation compared with wild-type (WT) plants, and enhancing drought tolerance of the transgenic plants. CONCLUSION: In this study, three candidate genes related to drought tolerance in potato were excavated, and the function of StPUB25 under drought stress was verified. These results should provide valuable information to understand the potato StPUB gene family and investigate the molecular mechanisms of StPUBs regulating potato drought tolerance.

Enhanced Uranium Extraction via Charge Dynamics and Interfacial Polarization in MoS2/GO Heterojunction Electrodes.

The removal of uranyl ions (UO2 2+) from water is challenging due to their chemical stability, low concentrations, complex water matrix, and technical limitations in extraction and separation. Herein, a novel molybdenum disulfide/graphene oxide heterojunction (MoS2/GO-H) is developed, serving as an effective electrode for capacitive deionization (CDI). By combining the inherent advantages of electroadsorption and electrocatalysis, an innovative electroadsorption-electrocatalysis system (EES) strategy is introduced. This system utilizes interface polarization at the MoS2 and GO interface, creating an additional electric field that significantly influences carrier behavior. The MoS2/GO-H electrode, with its extraordinary adsorption capacity of 805.57 mg g-1 under optimal conditions, effectively treated uranium-laden wastewater from a mine, achieving over 90% removal efficiency despite the presence of numerous competing ions at concentrations significantly higher than UO2 2+. Employing density functional theory (DFT) and ab initio molecular dynamics (AIMD) simulations, it is found that the MoS2/GO-H total charge density at the Fermi level, enhanced by interfacial polarization, surpasses that of separate MoS2 and GO, markedly boosting conductivity and electrocatalytic effectiveness.

Autoantibodies to BACE1 promote Aß accumulation and neurodegeneration in Alzheimer's disease.

The profile of autoantibodies is dysregulated in patients with Alzheimer's disease (AD). Autoantibodies to beta-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) are present in human blood. This study aims to investigate the clinical relevance and pathophysiological roles of autoantibodies to BACE1 in AD. Clinical investigations were conducted in two independent cohorts, the Chongqing cohort, and the Australian Imaging, Biomarkers, and Lifestyle (AIBL) cohort. The Chongqing cohort included 55 AD patients, 28 patients with non-AD dementia, and 70 cognitively normal subjects (CN). The AIBL cohort included 162 Aß-PET- CN, 169 Aß-PET+ cognitively normal subjects (preclinical AD), and 31 Aß-PET+ cognitively impaired subjects (Clinical AD). Plasma autoantibodies to BACE1 were determined by one-site Elisa. The associations of plasma autoantibodies to BACE1 with brain Aß load and cognitive trajectory were investigated. The effects of autoantibodies to BACE1 on AD-type pathologies and underlying mechanisms were investigated in APP/PS1 mice and SH/APPswe/PS1wt cell lines. In the Chongqing cohort, plasma autoantibodies to BACE1 were higher in AD patients, in comparison with CN and non-AD dementia patients. In the AIBL cohort, plasma autoantibodies to BACE1 were highest in clinical AD patients, followed by preclinical AD and CN subjects. Higher autoantibodies to BACE1 were associated with an increased incidence of brain amyloid positivity conversion during follow-up. Autoantibodies to BACE1 exacerbated brain amyloid deposition and subsequent AD-type pathologies, including Tau hyperphosphorylation, neuroinflammation, and neurodegeneration in APP/PS1 mice. Autoantibodies to BACE1 increased Aß production by promoting BACE1 expression through inhibiting PPARγ signaling. These findings suggest that autoantibodies to BACE1 are pathogenic in AD and the upregulation of these autoantibodies may promote the development of the disease. This study offers new insights into the mechanism of AD from an autoimmune perspective.

Interior and Exterior Surface Modification of Zr-Based Metal-Organic Frameworks for Trace Benzene Removal.

The emission of volatile organic compounds (VOCs) significantly contributes to air pollution and poses a serious threat to human health. Benzene, one of the most toxic VOCs, is difficult for the human body to metabolize and is classified as a Group 1 carcinogen. The development of efficient adsorbents for removing trace amounts of benzene from ambient air is thus of great importance. In this work, we studied the benzene adsorption properties of four Zr-based metal-organic frameworks (Zr-MOFs) through static volumetric and dynamic breakthrough experiments. Two previously reported Zr-MOFs, BUT-12 and STA-26, were prepared with a tritopic carboxylic acid ligand (H3L1) functionalized with three methyl groups, and STA-26 is a 2-fold interpenetrated network of BUT-12. Two new isoreticular Zr-MOFs, BUT-12-Et and STA-26-Et, were synthesized using a similar ligand, H3L2, where the methyl groups are replaced with ethyl groups. There are mesopores in BUT-12 and BUT-12-Et and micropores in STA-26 and STA-26-Et. The four Zr-MOFs all showed high stability in liquid water and acidic aqueous solutions. The microporous STA-26 and STA-26-Et showed much higher benzene uptakes than mesoporous BUT-12 and BUT-12-Et at room temperature under low pressures. Particularly, the benzene adsorption capacity of STA-26-Et was high up to 2.21 mmol/g at P/P0 = 0.001 (P0 = 12.78 kPa), higher than those of the other three Zr-MOFs and most reported solid adsorbents. Breakthrough experiments confirmed that STA-26-Et could effectively capture trace benzene (10 ppm) from dry air; however, its benzene capture capacity was reduced by 90% under humid conditions (RH = 50%). Coating of the crystals of STA-26-Et with polydimethylsiloxane (PDMS) increased the hydrophobicity of the exterior MOF surfaces, leading to a more than 2-fold improvement in its benzene capture capacity in the breakthrough experiment under humid condition. PDMS coating of STA-26-Et likely slowed down the water adsorption process, and thus, the adsorbent afforded more efficient capture of benzene. This work demonstrates that modifying both the interior and exterior surfaces of MOFs can effectively enhance their performance in capturing trace benzene from ambient air, even under humid conditions. This finding is meaningful for the development of new adsorbents for effective air purification applications.

Multifunctional Roles of Zinc in Cadmium Transport in Soil-Rice Systems: Novel Insights from Stable Isotope Fractionation and Gene Expression.

The effect of Zn on Cd accumulation in rice varies under flooding and drainage conditions, and the underlying mechanism during uptake and transport from the soil to grains remains unclear. Isotope fractionation and gene expression were investigated using pot experiments under distinct water regimes and with Zn addition to gain a deeper understanding of the molecular effects of Zn on Cd uptake and transport in rice. The higher OsHMA2 expression but constitutively lower expression of zinc-regulated, iron-regulated transporter-like protein (ZIP) family genes in roots under the drainage regime than the flooding regime caused the enrichment of nonheavy Zn isotopes in the shoots relative to roots but minimally affected Cd isotopic fractionation. Drainage regime seem to exert a striking effect on the root-to-shoot translocation of Zn rather than Cd, and increased Zn transport via OsHMA2. The changes in expression patterns in response to Zn addition were similar to those observed upon switching from the flooding to drainage regime, except for OsNRAMP1 and OsNRAMP5. However, soil solution-to-rice plants and root-to-shoot fractionation toward light Zn isotopes with Zn addition (Δ66Znrice plant-soil solution = -0.49 to -0.40‰, Δ66Znshoot-root = -0.36 to -0.27‰) indicated that Zn transport occurred via nonspecific uptake pathways and OsHMA2, respectively. Accordingly, the less pronounced and minimally varied Cd isotope fractionation suggested that OsNRAMP5 and OsHMA2 are crucial for Cd uptake and root-to-shoot transport, respectively, facilitating Cd accumulation in grains. This study demonstrated that a high Zn supply promotes Cd uptake and root-to-shoot transport in rice by sharing distinct pathways, and by utilizing a non-Zn-sensitive pathway with a high affinity for Cd.

Fluorescence quenching of deprotonated phenylurea through twisting motion induced by an electron-donating substituent group.

The excited-state proton transfer (ESPT) reaction between anthracen-2-yl-3-phenylurea (PUA) derivatives and tetrabutylammonium acetate (TBAAc) in dimethyl sulfoxide (DMSO) solvent was theoretically investigated using time-dependent density functional theory. The electron-donating methoxy group (OMe) and electron-withdrawing trifluoromethyl group (CF3) were bonded to 2PUA to form OMe-2PUA and CF3-2PUA, respectively. Two hydrogen bonds formed in the 1 : 1 hydrogen-bonded complexes between the 2PUA derivative and acetate ion (AcO-), namely N1-H1⋯O1 and N2-H2⋯O2. Strong charge transfer (CT) due to the electron-donating OMe group led to H1 transfer in the S1 state for the OMe-2PUA:AcO- hydrogen-bonded complex. On the contrary, weak CT due to the electron-withdrawing CF3 group led to H2 transfer in the S1 state for CF3-2PUA. After the ESPT reaction, the binding energies of the hydrogen-bonded complexes strongly decreased in both cases, and this promoted the separation of contact-ion pairs (CIPs*) and formed different types of anionic species. CF3-2PUA- could keep its nearly planar structure in the S1 state and emit "abnormal" fluorescence. On the other hand, the anionic OMe-2PUA- underwent a twisting motion to form a twisted structure in the S1 state with very low energy, and this led to a rapid internal conversion (IC) to quench long-wave fluorescence in the emission spectra.

Predictive nomograms of repeat intrahepatic recurrence and overall survival after radiofrequency ablation of recurrent colorectal liver metastases.

OBJECTIVES: This study was conducted to develop nomograms for predicting repeat intrahepatic recurrence (rIHR) and overall survival (OS), after radiofrequency ablation (RFA), treatment in patients with recurrent colorectal liver metastases (CLMs) after hepatectomy based on clinicopathologic features. METHODS: A total of 160 consecutive patients with recurrent CLMs after hepatectomy who were treated with ultrasound-guided percutaneous RFA from 2012 to 2022 were retrospectively included. Patients were randomly divided into a training cohort and a validation cohort, with a ratio of 8:2. Potential prognostic factors associated with rIHR and OS, after RFA, were identified by using the competing-risks and Cox proportional hazard models, respectively, and were used to construct the nomogram. The nomogram was evaluated by Harrell's C-index and a calibration curve. RESULTS: The 1-, 2-, and 3-year rIHR rates after RFA were 58.8%, 70.2%, and 74.2%, respectively. The 1-, 3- and 5-year OS rates were 96.3%, 60.4%, and 38.5%, respectively. In the multivariate analysis, mutant RAS, interval from hepatectomy to intrahepatic recurrence ≤ 12 months, CEA level >5 ng/ml, and ablation margin <5 mm were the independent predictive factors for rIHR. Mutant RAS, largest CLM at hepatectomy >3 cm, CEA level >5 ng/ml, and extrahepatic disease were independent predictors of poor OS. Two nomograms for rIHR and OS were constructed using the respective significant variables. In both cohorts, the nomogram demonstrated good discrimination and calibration. CONCLUSIONS: The established nomograms can predict individual risk of rIHR and OS after RFA for recurrent CLMs and contribute to improving individualized management.

Toxicokinetics and bioavailability of indoxacarb enantiomers and their new metabolites in rats.

Indoxacarb is a chiral insecticide that consists of two enantiomers, S-(+)-indoxacarb and R-(-)-indoxacarb, of which only S-(+)-indoxacarb has insecticidal activity. Previous enantioselective toxicology studies of indoxacarb focused mostly on simple environmental model organisms. The lack of a toxicology evaluation of indoxacarb conducted in a mammalian system could mean that the extent of the potential health risk posed by the insecticide to humans is not adequately known. In this study, we reported on a new pair of enantiomers, S-IN-RM294 and R-IN-RM294, derived from the metabolic breakdown of S-(+)-indoxacarb and R-(-)-indoxacarb, respectively, in rats. The toxicokinetics of S-(+)-indoxacarb, R-(-)-indoxacarb, S-IN-RM294, and R-IN-RM294 in rats were evaluated to provide a more comprehensive risk assessment of these molecules. The bioavailability and excretion rates of both S-(+)-indoxacarb and R-(-)-indoxacarb were relatively low, which may be due to their faster metabolism and accumulation in the tissues. In addition, there were significant differences in the metabolism and distribution between the two indoxacarb enantiomers and their metabolites in vivo. S-(+)-Indoxacarb was found to be more easily metabolized in the blood compared with R-(-)-indoxacarb, as shown by the differences in pharmacokinetic parameters between oral and intravenous administration. Analysis of their tissue distribution showed that S-(+)-indoxacarb was less likely to accumulate in most tissues. The results obtained for the two metabolites were consistent with those of the two parent compounds. S-IN-RM294 was more readily cleared from the blood and less likely to accumulate in the tissues compared with R-IN-RM294. Therefore, whether from the perspective of insecticidal activity or from the perspective of mammalian and environmental friendliness, the application of optically pure S-(+)-indoxacarb in agriculture may be a more efficient and safer strategy.

Suppression of Railway Catenary Galloping Based on Structural Parameters' Optimization.

Railway catenary galloping, induced by aerodynamic instability, poses a significant threat by disrupting the electric current connection through sliding contact with the contact wire. This disruption leads to prolonged rail service interruptions and damage to the catenary's suspension components. This paper delves into the exploration of optimizing the catenary system's structure to alleviate galloping responses, addressing crucial parameters such as span length, stagger dropper distribution, and tension levels. Employing a finite element model, the study conducts simulations to analyze the dynamic response of catenary galloping, manipulating structural parameters within specified ranges. To ensure accurate and comprehensive exploration, the Sobol sequence is utilized to generate low-discrepancy, quasi-random, and super-uniform distribution sequences for the high-dimensional parameter inputs. Subsequent to the simulation phase, a genetic algorithm based on neural networks is employed to identify optimal parameter settings for suppressing catenary galloping, taking into account various constraints. The results gleaned from this investigation affirm that adjusting structural parameters can effectively diminish the galloping amplitude of the railway catenary. The most impactful strategy involves augmenting tension and reducing span length. Moreover, even when tension and span length are fixed, adjusting other parameters demonstrates efficacy in reducing galloping amplitudes. The adjustment of messenger-wire tension, dropper distribution, and stagger can achieve a 22.69% reduction in the maximum vertical galloping amplitude. Notably, maintaining a moderate stagger value and a short steady arm-dropper distance is recommended to achieve the minimum galloping amplitude. This research contributes valuable insights into the optimization of railway catenary systems, offering practical solutions to mitigate galloping-related challenges and enhance overall system reliability.

Real-Time Optical Fiber Salinity Interrogator Based on Time-Domain Demodulation and TPMF Incorporated Sagnac Interferometer.

A novel demodulation scheme for a point-type fiber sensor is designed for salinity concentration monitoring based on a Sagnac interferometer (SI) composed of a tapered polarization-maintaining fiber (TPMF) and optical time stretching technology. The SI, constructed using a PMF with a taper region of 5.92 µm and an overall length of 30 cm, demonstrated a notable enhancement in the evanescent field, which intensifies the interaction between the light field and external salinity. This enhancement allows for a direct assessment of salinity concentration changes by analyzing the variations in the SI reflection spectra and the experimental results indicate that the sensitivity of the sensor is 0.151 nm/‱. In contrast to traditional fiber optic sensors that depend on spectral demodulation with slower response rates, this work introduces a new approach where the spectral shift is translated to the time domain, utilizing a dispersion compensation fiber (DCF) with the demodulation rate reaching up to 50 MHz. The experimental outcomes reveal that the sensor exhibits a sensitivity of -0.15 ns/‱ in the time domain. The designed sensor is anticipated to play a pivotal role in remote, real-time monitoring of ocean salinity.

Genome-Wide Identification of LOX Gene Family and Its Expression Analysis under Abiotic Stress in Potato (Solanum tuberosum L.).

The lipoxygenases (LOXs) are non-heme iron-containing dioxygenases that play an important role in plant growth and defense responses. There is scarce knowledge regarding the LOX gene family members and their involvement in biotic and abiotic stresses in potato. In this study, a total of 17 gene family members (StLOXs) in potato were identified and clustered into three subfamilies: 9-LOX type I, 13-LOX type I, and 13-LOX type II, with eleven, one, and five members in each subfamily based on phylogenetic analysis. By exploiting the RNA-seq data in the Potato Genome Sequencing Consortium (PGSC) database, the tissue-specific expressed and stress-responsive StLOX genes in double-monoploid (DM) potato were obtained. Furthermore, six candidate StLOX genes that might participate in drought and salt response were determined via qPCR analysis in tetraploid potato cultivars under NaCl and PEG treatment. Finally, the involvement in salt stress response of two StLOX genes, which were significantly up-regulated in both DM and tetraploid potato under NaCl and PEG treatment, was confirmed via heterologous expression in yeast under salt treatment. Our comprehensive analysis of the StLOX family provides a theoretical basis for the potential biological functions of StLOXs in the adaptation mechanisms of potato to stress conditions.

Overexpression of Potato PYL16 Gene in Tobacco Enhances the Transgenic Plant Tolerance to Drought Stress.

PYR/PYL/RCAR proteins are abscisic acid (ABA) receptors that play a crucial role in plant responses to abiotic stresses. However, there have been no research reports on potato PYL so far. In this study, a potato PYL gene named StPYL16 was identified based on transcriptome data under drought stress. Molecular characteristics analysis revealed that the StPYL16 protein possesses an extremely conserved PYL family domain. The tissue expression results indicated that the StPYL16 is predominantly expressed at high levels in the underground parts, particularly in tubers. Abiotic stress response showed that StPYL16 has a significant response to drought treatment. Further research on the promoter showed that drought stress could enhance the activation activity of the StPYL16 promoter on the reporter gene. Then, transient and stable expression of StPYL16 in tobacco enhanced the drought resistance of transgenic plants, resulting in improved plant height, stem thickness, and root development. In addition, compared with wild-type plants, StPYL16 transgenic tobacco exhibited lower malondialdehyde (MDA) content, higher proline accumulation, and stronger superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activities. Meanwhile, StPYL16 also up-regulated the expression levels of stress-related genes (NtSOD, NtCAT, NtPOD, NtRD29A, NtLEA5, and NtP5CS) in transgenic plants under drought treatment. These findings indicated that the StPYL16 gene plays a positive regulatory role in potato responses to drought stress.

Comprehensive Characterization of the C3HC4 RING Finger Gene Family in Potato (Solanum tuberosum L.): Insights into Their Involvement in Anthocyanin Biosynthesis.

The C3HC4 RING finger gene (RING-HC) family is a zinc finger protein crucial to plant growth. However, there have been no studies on the RING-HC gene family in potato. In this study, 77 putative StRING-HCs were identified in the potato genome and grouped into three clusters based on phylogenetic relationships, the chromosome distribution, gene structure, conserved motif, gene duplication events, and synteny relationships, and cis-acting elements were systematically analyzed. By analyzing RNA-seq data of potato cultivars, the candidate StRING-HC genes that might participate in tissue development, abiotic stress, especially drought stress, and anthocyanin biosynthesis were further determined. Finally, a StRING-HC gene (Soltu.DM.09G017280 annotated as StRNF4-like), which was highly expressed in pigmented potato tubers was focused on. StRNF4-like localized in the nucleus, and Y2H assays showed that it could interact with the anthocyanin-regulating transcription factors (TFs) StbHLH1 of potato tubers, which is localized in the nucleus and membrane. Transient assays showed that StRNF4-like repressed anthocyanin accumulation in the leaves of Nicotiana tabacum and Nicotiana benthamiana by directly suppressing the activity of the dihydroflavonol reductase (DFR) promoter activated by StAN1 and StbHLH1. The results suggest that StRNF4-like might repress anthocyanin accumulation in potato tubers by interacting with StbHLH1. Our comprehensive analysis of the potato StRING-HCs family contributes valuable knowledge to the understanding of their functions in potato development, abiotic stress, hormone signaling, and anthocyanin biosynthesis.

A Red-Emission Fluorescent Probe with Large Stokes Shift for Detection of Viscosity in Living Cells and Tumor-Bearing Mice.

Abnormal viscosity is closely related to the occurrence of many diseases, such as cancer. Therefore, real-time detection of changes in viscosity in living cells is of great importance. Fluorescent molecular rotors play a critical role in detecting changes in cellular viscosity. Developing red emission viscosity probes with large Stokes shifts and high sensitivity and specificity remains an urgent and important topic. Herein, a novel viscosity-sensitive fluorescent probe (TCF-VIS1) with a large stokes shift and red emission was prepared based on the 2-dicyanomethylene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran (TCF) skeleton. Due to intramolecular rotation, the probe itself does not fluorescence at low viscosity. With the increase in viscosity, the rotation of TCF-VIS1 is limited, and its fluorescence is obviously enhanced. The probe has the advantages of simple preparation, large Stokes shift, good sensitivity and selectivity, and low cytotoxicity, which make it successfully used for viscosity detection in living cells. Moreover, TCF-VIS1 showed its potential for cancer diagnosis at the cell level and in tumor-bearing mice by detecting viscosity. Therefore, the probe is expected to enrich strategies for the detection of viscosity in biological systems and offer a potential tool for cancer diagnosis.

[Daidzein attenuates high glucose-induced inflammatory injury in macrophages by regulating NLRP3 inflammasome signaling pathway].

This study aims to explore the inhibitory effect of daidzein on macrophage inflammation induced by high glucose via regulating the NOD-like receptor protein 3(NLRP3) inflammasome signaling pathway. The cell counting kit-8(CCK-8) assay was employed to detect the effects of daidzein at different concentrations on the viability of RAW264.7 cells. Western blot was employed to determine the protein level of tumor necrosis factor(TNF)-α in macrophages exposed to different concentrations of glucose for different time periods as well as the expression levels of proteins involved in the polarization and Toll-like receptor 4(TLR4)-myeloid differentiation factor(MyD88)-NLRP3 inflammasome pathway of the macrophages exposed to high glucose. Enzyme-linked immunosorbent assay was employed to measure the levels of TNF-α, interleukin(IL)-18, and IL-1ß secreted by macrophages. The expression level of nuclear factor-kappa B(NF-κB) p65 in macrophages exposed to high glucose was detected by immunofluorescence, and the level of intracellular reactive oxygen species(ROS) was detected by the DCFH-DA fluorescent probe. The mRNA levels of NLRP3, TNF-α, and IL-18 in macrophages were determined by qRT-PCR. The results showed that treatment with 30 mmol·L~(-1) glucose for 48 h was the best condition for the modeling of macrophage injury. Compared with the blank group, the model group showed improved polarization of macrophages, increased secretion of TNF-α, IL-18, and IL-1ß, elevated ROS level, and up-regulated expression of NF-κB p65. In addition, the modeling up-regulated the mRNA levels of NLRP3, TNF-α, and IL-18 and the protein levels of TLR4, MyD88, NLRP3, NF-κB p65, p-NF-κB p65, I-κB, p-I-κB, ASC, pro-caspase-1, pro-IL-1ß, cleaved IL-1ß, and pro-IL-18. Compared with the model group, daidzein(10, 20, and 40 µmol·L~(-1)) lowered the levels of inflammatory cytokines and down-regulated the mRNA levels of NLRP3, TNF-α, and IL-18 as well as the protein levels of TLR4, MyD88, NLRP3, NF-κB p65, p-NF-κB p65, I-κB, p-I-κB, ASC, pro-caspase-1, pro-IL-1ß, cleaved IL-1ß, and pro-IL-18. In addition, daidzein reduced intracellular ROS. According to the available reports and the experimental results, high glucose can induce the polarization of macrophages and promote the secretion of inflammatory cytokines. Daidzein can inhibit the expression of ROS in macrophages by regulating the NLRP3 inflammasome signaling pathway, thereby reducing the inflammation of macrophages exposed to high glucose.

Safety, tolerability, and pharmacokinetics of ibrexafungerp in healthy Chinese subjects: a randomized, double-blind, placebo-controlled phase 1 trial.

Ibrexafungerp (code name in China: HS-10366) is a first-in-class and orally active triterpenoid antifungal agent with broad antifungal activity against Candida spp., Aspergillus spp., and other fungal pathogens. It was approved by the U.S. Food and Drug Administration for the treatment of vulvovaginal candidiasis. The study aimed to evaluate the safety, tolerability, and pharmacokinetic (PK) characteristics of oral ibrexafungerp in healthy Chinese adults. A single-center, randomized, double-blind, placebo-controlled single ascending dose (SAD, n = 42), and multiple ascending dose (MAD, n = 28) study was conducted in healthy Chinese subjects from March to October 2022. There were three cohorts in the SAD stage (300, 600, and 1,500 mg) and two cohorts in the MAD stage [450 mg once daily (QD) for 7 days; a loading dose of 750 mg twice daily (BID) for the first 2 days followed by a maintenance dose of 750 mg QD for consecutive 5 days]. Eligible participants in each cohort were randomly assigned in a 6:1 ratio to receive either ibrexafungerp or placebo orally. The primary objectives were to evaluate the safety and tolerability. The secondary objective was to evaluate PK parameters, including Cmax, AUC, and t1/2. A total of 70 healthy Chinese subjects were enrolled in the study. The mean (SD) age was 29.0 (6.32), and 55.7% were male. All treatment-emergent adverse events (TEAEs) were mild or moderate. There were no serious adverse events, and no subjects were discontinued from the study due to TEAEs. All TEAEs were recovered or resolved. The most common TEAEs were diarrhea, abdominal pain, and nausea. In the SAD stage, Cmax, and AUC increased in an approximately dose-proportional manner in the dose range of 300-1,500 mg. The mean t1/2 was within 18.29-21.30 hours. In the MAD stage, an accumulation of exposure (Cmax and AUC) was observed following multiple doses. This phase 1 study demonstrates a favorable safety, tolerability, and PK profile of ibrexafungerp in healthy Chinese subjects.

Dendritic Plasmonic CuPt Alloys for Closed-Loop Multimode Cancer Therapy with Remarkably Enhanced Efficacy.

The outcome of laser-triggered plasmons-induced phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is significantly limited by the hypoxic tumor microenvironment and the upregulation of heat shock proteins (HSPs) in response to heat stress. Mitochondria, the biological battery of cells, can serve as an important breakthrough to overcome these obstacles. Herein, dendritic triangular pyramidal plasmonic CuPt alloys loaded with heat-sensitive NO donor N, N'-di-sec-butyl-N, N'-dinitroso-1,4-phenylenediamine (BNN) is developed. Under 808 nm laser irradiation, plasmonic CuPt can generate superoxide anion free radicals (·O2 - ) and heat simultaneously. The heat generated can then trigger the release of NO gas, which not only enables gas therapy but also damages the mitochondrial respiratory chain. Impaired mitochondrial respiration leads to reduced oxygen consumption and insufficient intracellular ATP supply, which effectively alleviates tumor hypoxia and undermines the synthesis of HSPs, in turn boosting plasmonic CuPt-based PDT and mild PTT. Additionally, the generated NO and ·O2 - can react to form more cytotoxic peroxynitrite (ONOO- ). This work describes a plasmonic CuPt@BNN (CPB) triggered closed-loop NO gas, free radicals, and mild photothermal therapy strategy that is highly effective at reciprocally promoting antitumor outcomes.

Compact optical fiber sensor based on Vernier effect with speckle patterns.

We propose a Vernier effect-based sensor for temperature and salinity measurements. This sensor utilizes the correlation speckle pattern generated by spatial multimode interference and has undergone testing to validate its effectiveness. The speckle demodulation method is used to solve the problem of inconsistent envelope measurement when tracking with different upper and lower envelopes. The device consists of two Fabry Perot interferometers (FPIs) created by connecting hole core fiber (HCF) and erbium-doped fiber (EDF) in series. The speckle image produced by the interferometers is analyzed using the Zero means normalized cross-correlation (ZNCC) technique. The ZNCC value demonstrates a linear relationship with salinity and temperature, allowing for the measurement of these parameters. The sensor exhibits a temperature detection sensitivity of -0.0224 /°C and a salinity detection sensitivity of -0.0439/%. The sensor offers several advantageous features, including its compact size, low-cost manufacturing, high sensitivity, stability, and convenient reflection measurements. These characteristics make it a valuable tool for various applications. The proposed Vernier effect-based temperature and salinity sensor shows great potential for simultaneous monitoring and measurement of temperature and salinity in environments such as marine settings or industrial processes where accurate control of these parameters is crucial.

Intratumoral and peritumoral radiomics based on contrast-enhanced MRI for preoperatively predicting treatment response of transarterial chemoembolization in hepatocellular carcinoma.

BACKGROUND: Noninvasive and precise methods to estimate treatment response and identify hepatocellular carcinoma (HCC) patients who could benefit from transarterial chemoembolization (TACE) are urgently required. The present study aimed to investigate the ability of intratumoral and peritumoral radiomics based on contrast-enhanced magnetic resonance imaging (CE-MRI) to preoperatively predict tumor response to TACE in HCC patients. METHODS: A total of 138 patients with HCC who received TACE were retrospectively included and randomly divided into training and validation cohorts at a ratio of 7:3. Total 1206 radiomics features were extracted from arterial, venous, and delayed phases images. The inter- and intraclass correlation coefficients, the spearman's rank correlation test, and the gradient boosting decision tree algorithm were used for radiomics feature selection. Radiomics models on intratumoral region (TR) and peritumoral region (PTR) (3 mm, 5 mm, and 10 mm) were established using logistic regression. Three integrated radiomics models, including intratumoral and peritumoral region (T-PTR) (3 mm), T-PTR (5 mm), and T-PTR (10 mm) models, were constructed using TR and PTR radiomics scores. A clinical-radiological model and a combined model incorporating the optimal radiomics score and selected clinical-radiological predictors were constructed, and the combined model was presented as a nomogram. The discrimination, calibration, and clinical utilities were evaluated by receiver operating characteristic curve, calibration curve, and decision curve analysis, respectively. RESULTS: The T-PTR radiomics models performed better than the TR and PTR models, and the T-PTR (3 mm) radiomics model demonstrated preferable performance with the AUCs of 0.884 (95%CI, 0.821-0.936) and 0.911 (95%CI, 0.825-0.975) in both training and validation cohorts. The T-PTR (3 mm) radiomics score, alkaline phosphatase, tumor size, and satellite nodule were fused to construct a combined nomogram. The combined nomogram [AUC: 0.910 (95%CI, 0.854-0.958) and 0.918 (95%CI, 0.831-0.986)] outperformed the clinical-radiological model [AUC: 0.789 (95%CI, 0.709-0.863) and 0.782 (95%CI, 0.660-0.902)] in the both cohorts and achieved good calibration capability and clinical utility. CONCLUSIONS: CE-MRI-based intratumoral and peritumoral radiomics approach can provide an effective tool for the precise and individualized estimation of treatment response for HCC patients treated with TACE.