Emergent charge order in pressurized kagome superconductor CsV3Sb5.

The discovery of several electronic orders in kagome superconductors AV3Sb5 (A means K, Rb, Cs) provides a promising platform for exploring unprecedented emergent physics1-9. Under moderate pressure (<2.2 GPa), the triple-Q charge density wave (CDW) order is monotonically suppressed by pressure, while the superconductivity shows a two-dome-like behaviour, suggesting an unusual interplay between superconductivity and CDW order10,11. Given that time-reversal symmetry breaking and electronic nematicity have been revealed inside the triple-Q CDW phase8,9,12,13, understanding this CDW order and its interplay with superconductivity becomes one of the core questions in AV3Sb5 (refs. 3,5,6). Here, we report the evolution of CDW and superconductivity with pressure in CsV3Sb5 by 51V nuclear magnetic resonance measurements. An emergent CDW phase, ascribed to a possible stripe-like CDW order with a unidirectional 4a0 modulation, is observed between Pc1 ≅ 0.58 GPa and Pc2 ≅ 2.0 GPa, which explains the two-dome-like superconducting behaviour under pressure. Furthermore, the nuclear spin-lattice relaxation measurement reveals evidence for pressure-independent charge fluctuations above the CDW transition temperature and unconventional superconducting pairing above Pc2. Our results not only shed new light on the interplay of superconductivity and CDW, but also reveal new electronic correlation effects in kagome superconductors AV3Sb5.

Charge-density-wave-driven electronic nematicity in a kagome superconductor.

Electronic nematicity, in which rotational symmetry is spontaneously broken by electronic degrees of freedom, has been demonstrated as a ubiquitous phenomenon in correlated quantum fluids including high-temperature superconductors and quantum Hall systems1,2. Notably, the electronic nematicity in high-temperature superconductors exhibits an intriguing entanglement with superconductivity, generating complicated superconducting pairing and intertwined electronic orders. Recently, an unusual competition between superconductivity and a charge-density-wave (CDW) order has been found in the AV3Sb5 (A = K, Rb, Cs) family with two-dimensional vanadium kagome nets3-8. Whether these phenomena involve electronic nematicity is still unknown. Here we report evidence for the existence of electronic nematicity in CsV3Sb5, using a combination of elastoresistance measurements, nuclear magnetic resonance (NMR) and scanning tunnelling microscopy/spectroscopy (STM/S). The temperature-dependent elastoresistance coefficient (m11 minus m12) and NMR spectra demonstrate that, besides a C2 structural distortion of the 2a0 × 2a0 supercell owing to out-of-plane modulation, considerable nematic fluctuations emerge immediately below the CDW transition (approximately 94 kelvin) and finally a nematic transition occurs below about 35 kelvin. The STM experiment directly visualizes the C2-structure-pinned long-range nematic order below the nematic transition temperature, suggesting a novel nematicity described by a three-state Potts model. Our findings indicate an intrinsic electronic nematicity in the normal state of CsV3Sb5, which sets a new paradigm for revealing the role of electronic nematicity on pairing mechanism in unconventional superconductors.

Arterial transit artifact as a short-term prognostic indicator in acute ischemic stroke.

BACKGROUND: Arterial transit artifact (ATA) observed on arterial spin labeling (ASL) was recently suggested to be associated with improved functional outcomes following acute ischemic stroke (AIS). AIS is a heterogeneous disease with diverse pathogenic mechanisms depending on the stroke subtype. This study aimed to investigate the association between ATA and 3-month functional outcomes in AIS patients according to etiology subtypes. METHODS: Consecutive patients with AIS were included. All patients underwent ASL MRI with postlabeling delay (PLD) of 1.5 and 2.5 s. ATA was assessed from the ASL images of both PLDs. Stroke etiologic subtypes were determined according to the modified TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification. Short-term functional outcomes were evaluated using the 3-month modified Rankin scale (mRS). Log-binomial regression was applied to analyze the association between ATA and functional outcomes at 3 months after stroke. RESULTS: Ninety-eight AIS patients (62.73 ± 13.05 years; 68 men) were finally included. ATA was detected in forty-six patients and most frequently seen in the large-artery atherosclerosis (LAA) subtype (35/46). The ATA group exhibited a lower percentage of patients with mRS > 2 compared to the group without ATA (36.5% vs. 19.6%; P < 0.001). ATA was independently associated with better 3-month clinical outcomes (adjusted risk ratio, 0.35[95% CI, 0.16-0.74]) in the multivariate log-binomial regression model. After stratification by TOAST subtypes, a significant association was found between ATA and better outcomes in the LAA subtype (adjusted risk ratio, 0.20[ 95% CI, 0.05-0.72]) but not in cardioembolism and small artery occlusion (SVO) subtype. CONCLUSION: ATA is associated with better outcomes at 3 months in patients with AIS, especially in the LAA subtype, but this association attenuated in the cardioembolism and SVO subtypes.

Vincamine alleviates brain injury by attenuating neuroinflammation and oxidative damage in a mouse model of Parkinson's disease through the NF-κB and Nrf2/HO-1 signaling pathways.

Parkinson's disease (PD) is a neurodegenerative disease featured by progressive loss of nigrostriatal dopaminergic neurons, the etiology of which is associated with the existence of neuroinflammatory response and oxidative stress. Vincamine is an indole alkaloid that was reported to exhibit potent anti-inflammatory and antioxidant properties in many central and/or peripheral diseases. Nevertheless, the specific role of vincamine in PD development remains unknown. In our study, dopaminergic neuron loss was determined through immunohistochemistry staining and western blot analysis of tyrosine hydroxylase (TH) expression in the substantia nigra (SN) of PD mice. Reactive oxygen species (ROS) production and malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) levels were detected through DHE staining and commercially available kits to assess oxidative stress. Pro-inflammatory cytokine (TNF-α, IL-1ß, and IL-6) levels in the SN were measured via RT-qPCR and western blot analysis. Microglial and astrocyte activation was examined through immunofluorescence staining of Iba-1 (microglia marker) and GFAP (astrocyte marker) in the SN. The regulation of vincamine on the NF-κB and Nrf2/HO-1 pathway was estimated through western blot analysis. Our results showed that vincamine treatment decreased TNF-α, IL-1ß, and IL-6 mRNA and protein levels, reduced GFAP and Iba-1 expression, decreased ROS production and MDA level, and increased SOD activity and GSH level in the SN of PD mice. Mechanically, vincamine repressed the phosphorylation levels of p65, IKKß, and IκBα but enhanced the protein levels of Nrf2 and HO-1 in PD mice. Collectively, vincamine plays a neuroprotective role in PD mouse models by alleviating neuroinflammation and oxidative damage via suppressing the NF-κB pathway and activating the Nrf2/HO-1 pathway.

Virtual Position Guided Strategy for Particle Swarm Optimization Algorithms on Multimodal Problems.

Premature convergence is a thorny problem for particle swarm optimization (PSO) algorithms, especially on multimodal problems, where maintaining swarm diversity is crucial. However, most enhancement strategies for PSO, including the existing diversity-guided strategies, have not fully addressed this issue. This paper proposes the virtual position guided (VPG) strategy for PSO algorithms. The VPG strategy calculates diversity values for two different populations and establishes a diversity baseline. It then dynamically guides the algorithm to conduct different search behaviors, through three phases - divergence, normal, and acceleration - in each iteration, based on the relationships among these diversity values and the baseline. Collectively, these phases orchestrate different schemes to balance exploration and exploitation, collaboratively steering the algorithm away from local optima and towards enhanced solution quality. The introduction of 'virtual position' caters to the strategy's adaptability across various PSO algorithms, ensuring the generality and effectiveness of the proposed VPG strategy. With a single hyperparameter and a recommended usual setup, VPG is easy to implement. The experimental results demonstrate that the VPG strategy is superior to several canonical and the state-of-the-art strategies for diversity guidance, and is effective in improving the search performance of most PSO algorithms on multimodal problems of various dimensionalities.

Functional Graphene for Peritumoral Brain Microenvironment Modulation Therapy in Glioblastoma.

Peritumoral brain invasion is the main target to cure glioblastoma. Chemoradiotherapy and targeted therapies fail to combat peritumoral relapse. Brain inaccessibility and tumor heterogeneity explain this failure, combined with overlooking the peritumor microenvironment. Reduce graphene oxide (rGO) provides a unique opportunity to modulate the local brain microenvironment. Multimodal graphene impacts are reported on glioblastoma cells in vitro but fail when translated in vivo because of low diffusion. This issue is solved by developing a new rGO formulation involving ultramixing during the functionalization with polyethyleneimine (PEI) leading to the formation of highly water-stable rGO-PEI. Wide mice brain diffusion and biocompatibility are demonstrated. Using an invasive GL261 model, an anti-invasive effect is observed. A major unexpected modification of the peritumoral area is also observed with the neutralization of gliosis. In vitro, mechanistic investigations are performed using primary astrocytes and cytokine array. The result suggests that direct contact of rGO-PEIUT neutralizes astrogliosis, decreasing several proinflammatory cytokines that would explain a bystander tumor anti-invasive effect. rGO also significantly downregulates several proinvasive/protumoral cytokines at the tumor cell level. The results open the way to a new microenvironment anti-invasive nanotherapy using a new graphene nanomaterial that is optimized for in vivo brain delivery.

Discovery of two ent-atisane diterpenoid lactones with AChE inhibitory activity from the roots of Euphorbia fischeriana.

Euphorlactone A (1), a rare rearranged ent-atisane norditerpenoid with an undescribed 3-nor-2,4-olide-ent-atisane scaffold, and euphorlactone B (2), a new ent-atisane diterpenoid with an unprecedented seven-membered lactone ring C, were isolated from the roots of Euphorbia fischeriana. Their planar structures with absolute configurations were extensively elucidated by analysis of 1D and 2D NMR data, electronic circular dichroism (ECD) calculations, Rh2(OCOCF3)4-induced ECD curves, and single-crystal X-ray diffraction. Euphorlactone A (ELA) showed a remarkable AChE (acetylcholinesterase) inhibitory activity (IC50 = 2.13 ± 0.06 µM and Ki = 0.058 µM), which was five times stronger than that of the positive control (rivastigmine, IC50 = 12.46 ± 0.82 µM), and further in vitro enzyme inhibition kinetic analysis and molecular docking studies were performed to investigate the AChE inhibitory mechanism.

Discovery of novel 2-(trifluoromethyl)quinolin-4-amine derivatives as potent antitumor agents with microtubule polymerization inhibitory activity.

In this work, a series of 2-(trifluoromethyl)quinolin-4-amine derivatives were designed and synthesized through structural optimization strategy as a microtubule-targeted agents (MTAs) and their cytotoxicity activity against PC3, K562 and HeLa cell lines were evaluated. The half maximal inhibitory concentration (IC50) of 5e, 5f, and 5o suggested that their potency of anti-proliferative activities against HeLa cell lines were better than the combretastatin A-4. Compound 5e showed the higher anti-proliferative activity against PC3, K562 and HeLa in vitro with IC50 values of 0.49 µM, 0.08 µM and 0.01 µM, respectively. Further mechanism study indicated that the representative compound 5e was new class of tubulin inhibitors by EBI competition assay and tubulin polymerization assays, it is similar to colchicine. Immunofluorescence staining revealed that compound 5e apparently disrupted tubulin network in HeLa cells, and compound 5e arrested HeLa cells at the G2/M phase and induced cells apoptosis in a dose-dependent manner. Molecular docking results illustrated that the hydrogen bonds of represented compounds reinforced the interactions in the pocket of colchicine binding site. Preliminary results suggested that 5e deserves further research as a promising tubulin inhibitor for the development of anticancer agents.

Recent development of gold(I) and gold(III) complexes as therapeutic agents for cancer diseases.

Metal complexes have demonstrated significant antitumor activities and platinum complexes are well established in the clinical application of cancer chemotherapy. However, the platinum-based treatment of different types of cancers is massively hampered by severe side effects and resistance development. Consequently, the development of novel metal-based drugs with different mechanism of action and pharmaceutical profile attracts modern medicinal chemists to design and synthesize novel metal-based agents. Among non-platinum anticancer drugs, gold complexes have gained considerable attention due to their significant antiproliferative potency and efficacy. In most situations, the gold complexes exhibit anticancer activities by targeting thioredoxin reductase (TrxR) or other thiol-rich proteins and enzymes and trigger cell death via reactive oxygen species (ROS). Interestingly, gold complexes were recently reported to elicit biochemical hallmarks of immunogenic cell death (ICD) as an ICD inducer. In this review, the recent progress of gold(I) and gold(III) complexes is comprehensively summarized, and their activities and mechanism of action are documented.

Deep Subspace Mutual Learning for cancer subtypes prediction.

MOTIVATION: Precise prediction of cancer subtypes is of significant importance in cancer diagnosis and treatment. Disease etiology is complicated existing at different omics levels; hence integrative analysis provides a very effective way to improve our understanding of cancer. RESULTS: We propose a novel computational framework, named Deep Subspace Mutual Learning (DSML). DSML has the capability to simultaneously learn the subspace structures in each available omics data and in overall multi-omics data by adopting deep neural networks, which thereby facilitates the subtype's prediction via clustering on multi-level, single-level and partial-level omics data. Extensive experiments are performed in five different cancers on three levels of omics data from The Cancer Genome Atlas. The experimental analysis demonstrates that DSML delivers comparable or even better results than many state-of-the-art integrative methods. AVAILABILITY AND IMPLEMENTATION: An implementation and documentation of the DSML is publicly available at https://github.com/polytechnicXTT/Deep-Subspace-Mutual-Learning.git.

Natural product myricetin is a pan-KDM4 inhibitor which with poly lactic-co-glycolic acid formulation effectively targets castration-resistant prostate cancer.

BACKGROUND: Castration-resistant prostate cancer (CRPC) with sustained androgen receptor (AR) signaling remains a critical clinical challenge, despite androgen depletion therapy. The Jumonji C-containing histone lysine demethylase family 4 (KDM4) members, KDM4A‒KDM4C, serve as critical coactivators of AR to promote tumor growth in prostate cancer and are candidate therapeutic targets to overcome AR mutations/alterations-mediated resistance in CRPC. METHODS: In this study, using a structure-based approach, we identified a natural product, myricetin, able to block the demethylation of histone 3 lysine 9 trimethylation by KDM4 members and evaluated its effects on CRPC. A structure-based screening was employed to search for a natural product that inhibited KDM4B. Inhibition kinetics of myricetin was determined. The cytotoxic effect of myricetin on various prostate cancer cells was evaluated. The combined effect of myricetin with enzalutamide, a second-generation AR inhibitor toward C4-2B, a CRPC cell line, was assessed. To improve bioavailability, myricetin encapsulated by poly lactic-co-glycolic acid (PLGA), the US food and drug administration (FDA)-approved material as drug carriers, was synthesized and its antitumor activity alone or with enzalutamide was evaluated using in vivo C4-2B xenografts. RESULTS: Myricetin was identified as a potent α-ketoglutarate-type inhibitor that blocks the demethylation activity by KDM4s and significantly reduced the proliferation of both androgen-dependent (LNCaP) and androgen-independent CRPC (CWR22Rv1 and C4-2B). A synergistic cytotoxic effect toward C4-2B was detected for the combination of myricetin and enzalutamide. PLGA-myricetin, enzalutamide, and the combined treatment showed significantly greater antitumor activity than that of the control group in the C4-2B xenograft model. Tumor growth was significantly lower for the combination treatment than for enzalutamide or myricetin treatment alone. CONCLUSIONS: These results suggest that myricetin is a pan-KDM4 inhibitor and exhibited potent cell cytotoxicity toward CRPC cells. Importantly, the combination of PLGA-encapsulated myricetin with enzalutamide is potentially effective for CRPC.

Platelet MicroRNA 365-3p Expression Correlates with High On-treatment Platelet Reactivity in Coronary Artery Disease Patients.

PURPOSE: The expression level of platelet microRNAs (miRNAs) correlates with heart disease and may be altered by antiplatelet therapy. This study aims to assess whether certain miRNAs are associated with treatment response by platelets in patients who received percutaneous coronary intervention and antiplatelet therapy. The dynamic expression of certain miRNAs in patients receiving different antiplatelet regimens was also investigated. METHODS: Healthy subjects (N = 20) received no-stent or antiplatelet therapy (as control), and patients (N = 155) who underwent stent implant and received treatment regimens that included aspirin plus clopidogrel, ticagrelor, or cilostazol were included. The association of miR-96-5p, miR-495-3p, miR-107, miR-223-3p, miR-15a-5, miR-365-3p, and miR-339-3p levels with treatment response, SYNTAX score, and HTPR was determined. RESULTS: Of the different treatment regimens, ticagrelor was the most efficacious. At 24 h following drug administration, ROC analysis revealed that miR-339-3p and miR-365-3p had the highest sensitivity (74.3% and 90.0%, respectively) and specificity (71.4% and 93.3%) for detecting HTPR compared with the five other miRNAs. The SYNTAX score positively correlated with miR-223-3p and miR-365-3p levels at 24 h (P ≤ 0.006) and with miR-365-3p levels 7 days following drug administration (P = 0.014). The expression of all three miRNAs reached the highest levels in hyperresponsive (P2Y12 reaction unit < 85) followed by hyporesponsive (P2Y12 reaction unit ≥ 208) and then normoreactive. The normoreactive value was very close to that of controls. CONCLUSIONS: Our data suggest that miR-365-3p expression level correlates with the antiplatelet treatment response. CLINICAL TRIAL REGISTRATION: NCT02101437.

Fluorescence Quenching Investigation of Methyl Red Adsorption on Aluminum-Based Metal-Organic Frameworks.

The adsorption of methyl red (MR) isomers (ortho, meta, and para) on metal-organic frameworks (MOFs) was investigated by using a fluorescence quenching technique. All three MR isomers were found to quench the fluorescence of MOFs effectively. Nonlinear fluorescence quenching trends were observed in Stern-Volmer plots. A modified nonlinear Stern-Volmer equation with the concepts of multiple adsorption sites, adsorption strength, and quencher accessibility was successfully adopted to fit the fluorescence quenching data. The fitted parameters were correlated with the structural properties of MRs and MOFs. The order of quenching efficiency was found to be m-MR > p-MR > o-MR for all MOFs. This indicates that MR molecules not only adsorb via carboxylate-metal bonding but also adsorb through π-π interactions between the aromatic rings of MR and linker molecules in MOFs. The position of the carboxylate group in MRs and the structure of the linkers in MOFs are the key factors affecting the fluorescence quenching efficiency.

Optimum Wing Shape Determination of Highly Flexible Morphing Aircraft for Improved Flight Performance.

In this paper, optimum wing bending and torsion deformations are explored for a mission adaptive, highly flexible morphing aircraft. The complete highly flexible aircraft is modeled using a strain-based geometrically nonlinear beam formulation, coupled with unsteady aerodynamics and 6-dof rigid-body motions. Since there are no conventional discrete control surfaces for trimming the flexible aircraft, the design space for searching the optimum wing geometries is enlarged. To achieve high performance flight, the wing geometry is best tailored according to the specific flight mission needs. In this study, the steady level flight and the coordinated turn flight are considered, and the optimum wing deformations with the minimum drag at these flight conditions are searched by utilizing a modal-based optimization procedure, subject to the trim and other constraints. The numerical study verifies the feasibility of the modal-based optimization approach, and shows the resulting optimum wing configuration and its sensitivity under different flight profiles.

Anisotropic Spin Fluctuations Induced by Spin-Orbit Coupling in a Misfit Layer Compound (LaSe)1.14(NbSe2).

Spin-orbit coupling (SOC) has significant effects on the superconductivity and magnetism of transition metal dichalcogenides (TMDs) at the 2D limit. Although 2D TMD samples possess many exotic properties different from those of bulk samples, experimental characterization in this field is still limited, especially for magnetism. Recent studies have revealed that bulk misfit layer compounds (MLCs) with (LaSe)1.14(NbSe2)n = 1,2 exhibit an Ising superconductivity similar to that of heavily electron-doped NbSe2 monolayers. This offers an opportunity to study the effect of SOC on the magnetism of 2D TMDs. Here, the possible SOC effect in (LaSe)1.14(NbSe2) is investigated by measuring nuclear magnetic resonance (NMR) and electrical transport. It is found that the LaSe layer not only functions as a charge reservoir for transferring electrons into the NbSe2 layer but also remarkably influences the local electronic environment around the 93Nb nuclei. More importantly, the significant SOC induces both a weak antilocalization (WAL) effect and anisotropic spin fluctuations in noncentrosymmetric NbSe2 layers. The present work contributes to a deep understanding of the role of the SOC effect in 2D TMDs and supports MCLs as an intriguing platform for exploring exotic physical properties within the 2D limit.

Potent antitumor activity of anti-HER2 antibody-topoisomerase I inhibitor conjugate based on self-immolative dendritic dimeric-linker.

Antibody-drug conjugates (ADCs) are a rapidly expanding class of anticancer therapeutics, with 14 ADCs already approved worldwide. We developed unique linker technologies for the bioconjugation of drug molecules with controlled-release applications. We synthesized cathepsin-cleavable ADCs using a dimeric prodrug system based on a self-immolative dendritic scaffold, resulting in a high drug-antibody ratio (DAR) with the potential to reach 16 payloads due to its dendritic structure, increased stability in the circulation and efficient release profile of a highly cytotoxic payload at the targeted site. Using our novel cleavable linker technologies, we conjugated the anti-human epidermal growth factor receptor 2 (anti-HER2) antibody, trastuzumab, with topoisomerase I inhibitors, exatecan or belotecan. The newly synthesized ADCs were tested in vitro on mammary carcinoma cells overexpressing human HER2, demonstrating a substantial inhibitory effect on the proliferation of HER2-positive cells. Importantly, a single dose of our trastuzumab-based ADCs administered in vivo to mice bearing HER2-positive tumors, showed a dose-dependent inhibition of tumor growth and survival benefit, with the most potent antitumor effects observed at 10 mg/kg, which resulted in complete tumor regression and survival of 100% of the mice. Overall, our novel dendritic technologies using the protease-cleavable Val-Cit linker present an opportunity for the development of highly selective and potent controlled-released therapeutic payloads. This strategy could potentially lead to the development of novel and effective ADC technologies for patients diagnosed with HER2-positive cancers. Moreover, our proposed ADC linker technology can be implemented in additional medical conditions such as other malignancies as well as autoimmune diseases that overexpress targets, other than HER2.

Inflammatory factors gene polymorphism in recurrent oral ulceration.

BACKGROUND: Some inflammatory factors play an important role in recurrent oral ulceration (ROU). The genetics mechanism of expression level of inflammatory factors is not clear in ROU, but from genetics the expression level of inflammatory factors at least partly depend on the gene polymorphisms. Therfore, we decided to investigate inflammatory factors gene polymorphism and its association with the susceptibility of recurrent oral ulceration in Chinese. METHODS: Genomic DNA was obtained from 42 subjects with recurrent oral ulceration, 86 subjects of healthy control individuals.Genotypes and alleles of 10 genes and 17 polymorphisms sites were analyzed by Mass-ARRAY Analyzer method. Then, the differences in distribution of each genotype and allele were compared. RESULTS: The statistical differences in distribution of TNF-α (rs1800629 and rs1800630) genotype and allele were observed among the groups with recurrent oral ulceration and healthy control individuals (P < 0.01), while VEGFA (rs1570360, rs833061, and rs2010963), EGF (rs4444903), TNF (rs361525), IL10 (rs1800896, rs1800872), IL2 (rs2069762), IL4 (rs2243250), Fas (rs1800682, rs2234767), IL12A (rs2243115, rs568408), IL12B (rs3212227), and IFNG (rs2430561) showed no statistical differences of genotype and allele in controls as compared to those in patients. CONCLUSIONS: This study suggests that the TNF-α (rs1800629 and rs1800630) genotype is an indicator for the susceptibility of recurrent oral ulceration.

NSAID-Au(I) Complexes Induce ROS-Driven DAMPs and Interpose Inflammation to Stimulate the Immune Response against Ovarian Cancer.

Inflammation contributes to the development of ovarian cancer, and chemoresistance is a principal obstacle in ovarian cancer treatment. Herein, we designed and synthesized a series of gold(I) complexes derived from NSAIDs or their analogues. Among them, complex B3 (Npx-Au) displayed higher antitumor activity than cisplatin and other gold(I) complexes. Npx-Au could induce oxidative stress and the damage-associated molecular patterns (DAMPs) process by the inhibition of TrxR activity. Mechanistic studies revealed that simultaneous downregulation of COX-2 and PD-L1 was observed after Npx-Au treatment. Interestingly, in vivo experiments demonstrated that Npx-Au treatment could stimulate the immune response via reducing the expression of PD-L1, inducing DC maturation and increasing the infiltration of T (CD4+ and CD8+) cells. Collectively, our studies found that the gold(I) complex Npx-Au could elicit immunogenic cell death (ICD) and provide a promising strategy for chemotherapy combined with immunotherapy in the treatment of ovarian cancer.

High-Throughput Color Imaging Hg2+ Sensing via Amalgamation-Mediated Shape Transition of Concave Cube Au Nanoparticles.

Mercury, as one type of toxic heavy metal, represents a great threat to environmental and biological metabolic systems. Thus, reliable and sensitive quantitative detection of mercury levels is particularly meaningful for environmental protection and human health. We proposed a high-throughput single-particle color imaging strategy under dark-field microscopy (DFM) for mercury ions (Hg2+) detection by using individual concave cube Au nanoparticles as optical probes. In the presence of ascorbic acid (AA), Hg2+ was reduced to Hg which forms Au-Hg amalgamate with Au nanoparticles, altering their localized surface plasmon resonance (LSPR). Transmission electron microscopy (TEM) images demonstrated that the concave cube Au nanoparticles were approaching to sphere upon increasing the concentration of Hg2+. The nanoparticles underwent an obvious color change from red to yellow, green, and finally blue under DFM due to the shape-evolution and LSPR changes. In addition, we demonstrated for the first time that the LSPR of Au-Hg amalgamated below 400 nm. Inspired by the above-mentioned results, single-particle color variations were digitalized by converting the color image into RGB channels to obtain (green+blue)/red intensity ratios [(G+B)/R]. The concentration-dependence change was quantified by statistically analyzing the (G+B)/R ratios of a large number of particles. A linear range from 10 to 2000 nM (R2 = 0.972) and a limit of detection (LOD) of 1.857 nM were acquired. Furthermore, many other metal ions, like Cu2+, Cr3+, etc., did not interfere with Hg2+ detection. More importantly, Hg2+ content in industrial wastewater samples and in the inner regions of human HepG2 cells was determined, showing great potential for developing a single-particle color imaging sensor in complex biological samples using concave cube Au nanoparticles as optical probes.

Ursolic acid inhibits Th17 cell differentiation via STAT3/RORγt pathway and suppresses Schwann cell-mediated Th17 cell migration by reducing CXCL9/10 expression.

Th17 cells represent important immune cells. Ursolic acid (UA) can regulate immune cell activities. This study was aimed to explore the effects of UA on Th17 cell differentiation and Schwann cell(SCs)-mediated migration and the potential mechanism. Naïve CD4+ T cells were isolated from rat peripheral blood, induced for Th17 cell differentiation, and treated with UA. The proportion of Th17 cells was detected by flow cytometry assay. SCs were co-cultured with Th17 cells. Th17 cell migration was detected by Transwell assay. The molecule expression was determined by Western blot and qRT-PCR. UA inhibited the Th17 cell differentiation and suppressed the STAT3/RORγt pathway. STAT3 overexpression up-regulated p-STAT3 and RORγt expression and promoted Th17 cell differentiation under the UA treatment. In LPS- and IFN-γ-stimulated-SCs, UA suppressed the expression of chemokines CXCL9/10, but had no significant effect of CCL20 expression. The expression CXCL9/10 receptor CXCR3 was higher in Th17 cells than that in Treg cells, while the expression CCL20 receptor CCR6 was lower in Th17 cells than that in Treg cells. UA, anti-CXCR3, and anti-CCR6 treatment inhibited SCs-mediated Th17 cell migration, and anti-CXCR3 exerted stronger inhibitory effect than Anti-CCR6. UA inhibited Th17 cell differentiation through STAT3/RORγt pathway and suppressed Th17 cell migration through down-regulating CXCL9/10 expression in SCs.