Norcantharidin Enhances the Antitumor Effect of 5-Fluorouracil by Inducing Apoptosis of Cervical Cancer Cells: Network Pharmacology, Molecular Docking, and Experimental Validation.

The high recurrence rate of cervical cancer is a leading cause of cancer deaths in women. 5-Fluorouracil (5-FU) is an antitumor drug used to treat many types of cancer, but its diminishing effectiveness and side effects limit its use. Norcantharidin (NCTD), a demethylated derivative of cantharidin, exhibits various biological activities. Here, we investigated whether NCTD could potentiate 5-FU to induce cervical cancer cell death. To assess the cell viability and synergistic effects of the drugs, cell counting kit-8 and colony formation assays were performed using HR-HPV-positive cervical cancer cell lines. Annexin V-FITC/PI staining and TUNEL assays were performed to confirm the induction of apoptosis. The synergistic effect of NCTD on the antitumor activity of 5-FU was analyzed using network pharmacology, molecular docking, and molecular dynamics simulations. Apoptosis-related proteins were examined using immunoblotting. The combination of NCTD and 5-FU was synergistic in cervical cancer cell lines. Network pharmacological analysis identified 10 common targets of NCTD and 5-FU for cervical cancer treatment. Molecular docking showed the strong binding affinity of both compounds with CA12, CASP9, and PTGS1. Molecular dynamics simulations showed that the complex system of both drugs with caspase-9 could be in a stable state. NCTD enhanced 5-FU-mediated cytotoxicity by activating apoptosis-related proteins. NCTD acts synergistically with 5-FU to inhibit cervical cancer cell proliferation. NCTD enhances 5-FU-induced apoptosis in cervical cancer cell lines via the caspase-dependent pathway.

Laser-induced dynamic alignment and nonlinear-like optical transmission in liquid suspensions of 2D atomically thin nanomaterials.

Nonlinear optical property of atomically thin materials suspended in liquid has attracted a lot of attention recently due to the rapid development of liquid exfoliation methods. Here we report laser-induced dynamic orientational alignment and nonlinear-like optical response of the suspensions as a result of their intrinsic anisotropic properties and thermal convection of solvents. Graphene and graphene oxide suspensions are used as examples, and the transition to ordered states from initial optically isotropic suspensions is revealed by birefringence imaging. Computational fluid dynamics is performed to simulate the velocity evolution of convection flow and understand alignment-induced birefringence patterns. The optical transmission of these suspensions exhibits nonlinear-like saturable or reverse saturable absorptions in Z-scan measurements with both nanosecond and continuous-wave lasers. Our findings not only demonstrate a non-contact controlling of macroscopic orientation and collective optical properties of nanomaterial suspensions by laser but also pave the way for further explorations of optical properties and novel device applications of low-dimensional nanomaterials.

[Thermosensitive gel of polysaccharide from Ganoderma applanatum combined with paclitaxel for mice with 4T1 breast cancer].

Polysaccharide from Ganoderma applanatum has the activities of anti-tumor and enhancing immune function. There were no reports on antitumor effect of its intratumoral injection. In this study, the polysaccharide was extracted from G. applanatum by water extraction and alcohol precipitation, and purified by ceramic membrane after removing protein by Sevage method. The total polysaccharide content from G. applanatum(PGA)was about 63%. The combination of PGA and paclitaxel showed synergistic effect on cytotoxicity of 4 T1 cells at lower concentrations in vitro. In addition, the growth curve of 4 T1 cells showed that PGA could retard the growth of 4 T1 cells gradually. The PGA thermosensitive gel(PGA-TG)was prepared by using poloxamer 188 and 407. The gel temperature was 36 ℃, and the PGA-TG could effectively slow down the release rate of PGA in vitro. 4 T1 breast cancer-bearing mice were used as a model to evaluate the therapeutic effect of intratumoral injection of PGA combined with tail vein injection of nanoparticle albumin-bound paclitaxel(nab-PTX). In high and low dose PGA groups, each mice was given with 2.25, 1.125 mg PGA respectively, twice in total, and the dosage of paclitaxel was 15 mg·kg~(-1), once every 3 days, for a total of five times. The tumor inhibition rate was 29.65% in the high dose PGA-TG group, 58.58% in the nab-PTX group, 63.37% in low dose PGA-TG combined with nab-PTX group, and 68.10% in high dose PGA-TG combined with nab-PTX group respectively. The inhibitory effect in high dose PGA-TG group combined with nab-PTX on tumors was significantly higher than that in nab-PTX group(P<0.05). The results showed that paclitaxel therapy combined with intratumoral injection of PGA-TG could improve the therapeutic effect for 4 T1 mice and reduce the side effects of chemotherapy.

Higher thermoelectric performance of Zintl phases (Eu0.5Yb0.5)1-xCaxMg2Bi2 by band engineering and strain fluctuation.

Complex Zintl phases, especially antimony (Sb)-based YbZn0.4Cd1.6Sb2 with figure-of-merit (ZT) of ∼1.2 at 700 K, are good candidates as thermoelectric materials because of their intrinsic "electron-crystal, phonon-glass" nature. Here, we report the rarely studied p-type bismuth (Bi)-based Zintl phases (Ca,Yb,Eu)Mg2Bi2 with a record thermoelectric performance. Phase-pure EuMg2Bi2 is successfully prepared with suppressed bipolar effect to reach ZT ∼ 1. Further partial substitution of Eu by Ca and Yb enhanced ZT to ∼1.3 for Eu0.2Yb0.2Ca0.6Mg2Bi2 at 873 K. Density-functional theory (DFT) simulation indicates the alloying has no effect on the valence band, but does affect the conduction band. Such band engineering results in good p-type thermoelectric properties with high carrier mobility. Using transmission electron microscopy, various types of strains are observed and are believed to be due to atomic mass and size fluctuations. Point defects, strain, dislocations, and nanostructures jointly contribute to phonon scattering, confirmed by the semiclassical theoretical calculations based on a modified Debye-Callaway model of lattice thermal conductivity. This work indicates Bi-based (Ca,Yb,Eu)Mg2Bi2 is better than the Sb-based Zintl phases.

Steric and Electronic Influence of Aryl Isocyanides on the Properties of Iridium(III) Cyclometalates.

Cyclometalated iridium complexes with efficient phosphorescence and good electrochemical stability are important candidates for optoelectronic devices. Isocyanide ligands are strong-field ligands: when attached to transition metals, they impart larger HOMO-LUMO energy gaps, engender higher oxidative stability at the metal center, and support rugged organometallic complexes. Aryl isocyanides offer more versatile steric and electronic control by selective substitution at the aryl ring periphery. Despite a few reports of alkyl isocyanide of cyclometalated iridium(III), detailed studies on analogous aryl isocyanide complexes are scant. We report the synthesis, photophysical properties, and electrochemical properties of 11 new luminescent cationic biscyclometalated bis(aryl isocyanide)iridium(III) complexes. Three different aryl isocyanides--2,6-dimethylphenyl isocyanide (CNAr(dmp)), 2,6-diisopropylphenyl isocyanide (CNAr(dipp)), and 2-naphthyl isocyanide (CNAr(nap))--were combined with four cyclometalating ligands with differential π-π* energies--2-phenylpyridine (ppy), 2,4-difluorophenylpyridine (F2ppy), 2-benzothienylpyridine (btp), and 2-phenylbenzothiazole (bt). Five of them were crystallographically characterized. All new complexes show wide redox windows, with reduction potentials falling in a narrow range of -2.02 to -2.37 V and oxidation potentials spanning a wider range of 0.97-1.48 V. Efficient structured emission spans from the blue region for [(F2ppy)2Ir(CNAr)2]PF6 to the orange region for [(btp)2Ir(CNAr)2]PF6, demonstrating that isocyanide ligands can support redox-stable luminescent complexes with a range of emission colors. Emission quantum yields were generally high, reaching a maximum of 0.37 for two complexes, whereas btp-ligated complexes had quantum yields below 1%. The structure of the CNAr ligand has a minimal effect on the photophysical properties, which are shown to arise from ligand-centered excited states with very little contribution from metal-to-ligand charge transfer in most cases.

Identifying Factors Contributing to Delayed Diagnosis of Ovarian Cancer: A Comprehensive Analysis.

Background: Ovarian cancer (OC) remains the deadliest gynecologic malignancy worldwide due to delayed diagnosis, recurrence, and drug resistance. This study aimed to identify key factors affecting delayed diagnosis in OC patients. Methods: A retrospective analysis was conducted on OC patients treated at Taihe Hospital, Hubei University of Medicine from June 2023 to September 2023. Patients were categorized based on a three-months cut-off point for delayed diagnosis. Collected data included demographics, tumor incidence, and disease cognition. The analysis of variance and the chi-squared test was used for comparison between groups. Results: The significant differences were found in age, residence, education level, family income, family history of tumor, histology, FIGO stage, and tumor location between groups (P<0.05). Multifactorial logistic regression analysis identified education level [odds ratio (OR) = 0.606; 95% confidence interval (CI): 0.440, 0.833; P = 0.002], family history of tumor (OR = 0.462; 95% CI: 0.214, 0.997; P = 0.049), emotional barriers (OR = 1.332; 95% CI: 1.081, 1.642; P = 0.007), and practical barriers (OR = 2.964; 95% CI: 2.195, 4.004; P < 0.001) as risk factors for delayed diagnosis of OC. Conclusion: Patient cognition is crucial in OC diagnosis delay. Enhancing public awareness and understanding of OC is essential to eliminate fear and improve early diagnosis.

The Association Between Triglyceride Glucose-Body Mass Index and Kidney Impairment in Patients with Type 2 Diabetes Mellitus.

Purpose: Insulin resistance is associated with kidney impairment in patients with type 2 diabetes mellitus (T2DM). The triglyceride glucose-body mass index (TyG-BMI), which combines the TyG index with body mass index (BMI), has received significant attention as a tool for evaluating insulin resistance. Thus, the aim of this study was to explore the association between TyG-BMI and kidney impairment in patients with type 2 diabetes mellitus (T2DM). Patients and Methods: The cross-sectional analysis included 1080 patients with T2DM, and data were collected retrospectively. TyG-BMI was calculated by fasting blood glucose, triglyceride, and body mass index. Results: TyG-BMI was significantly higher in T2DM patients with albuminuria than those without albuminuria (232.16 [206.52-268.02] vs 229.83 [206.11-255.64], p =0.023). T2DM patients with chronic kidney disease (CKD) showed a significantly higher value of TyG-BMI compared with those without CKD (232.23 [206.46-268.28] vs 229.73 [206.11-255.49], p=0.014). Correlation analysis showed a significantly positive association between TyG-BMI and metabolic parameters including BMI (r = 0.866, p < 0.001), TG (r = 0.630, p < 0.001), TC (r = 0.119, p < 0.001), HDL-C (r = -0.374, p < 0.001), FBG (r = 0.297, p < 0.001), and HbA1c (r = 0.116, p < 0.001) in patients with T2DM. The binary logistic regression analysis found that TyG-BMI was an independent factor for albuminuria (OR = 1.004, 95% CI: 1.001-1.008, p = 0.010) and CKD (OR = 1.005, 95% CI: 1.001-1.008, p = 0.005) in patients with T2DM respectively. Conclusion: The study suggests that TyG-BMI is associated with kidney impairment in patients with T2DM. Given that TyG-BMI is a novel parameter of insulin resistance, the study results indicates that clinicians should pay close attention to screening for kidney impairment in T2DM patients with insulin resistance.

Can Peripheral Group Members Not Represent the In-Group? The Effect of Member Prototypicality on Intergroup Conflict.

Group member prototypicality is a factor in intergroup conflict-not all group members fight for group interests. This study focuses on the role of peripheral group members and the factors that influence their participation. We conducted two studies to examine the effects of group acceptance and self-uncertainty on the relationship between prototypicality and intergroup conflict. Results indicate that group acceptance moderates the relationship between prototypicality and intergroup conflict. Self-uncertainty moderates the effect of the interaction between prototypicality and group acceptance on intergroup conflict. Our findings have theoretical and practical implications for intergroup conflict resolution.

Percolating conductive networks in multiwall carbon nanotube-filled polymeric nanocomposites: towards scalable high-conductivity applications of disordered systems.

Disordered polymeric composite systems ordinarily exhibit poor bulk electronic transport properties, restricting their use to low-conductivity applications. In this work, highly electroconductive multi-walled carbon nanotube (MWCNT)/polyurethane (PU) nanocomposites were assembled via an aqueous solvent-blending method. Low percolation thresholds of 0.001 wt% and 0.093 wt% were obtained using pristine MWCNTs (P-MWCNTs) and mildly oxidized MWCNTs (O-MWCNTs), respectively. Corresponding critical values of dimensionality of 2.067 ± 0.094 and 2.304 ± 0.114 were calculated for P-MWCNT/PU and O-MWCNT/PU composites, respectively, strongly suggesting the formation of three-dimensional percolating conductive networks permeating the PU host matrix above the percolation threshold. Saturated direct current conductivities as high as 839 ± 72 S cm-1 were measured for O-MWCNT/PU composites at a filler-loading of 30.9 wt%. MWCNT/PU composite surfaces functionalized with superhydrophobic perfluoroalkyl moieties via chemical vapor deposition of (tridecafluoro-1,1,2,2-tetrahydrooctyl)trichlorosilane exhibited sessile contact angles as high as 154° without adversely affecting electroconductivity.

Distinguishing thermal lens effect from electronic third-order nonlinear self-phase modulation in liquid suspensions of 2D nanomaterials.

The interaction of light with atomically thin nanomaterials has attracted enormous research interest in order to understand two-dimensional (2D) electron systems and develop novel opto-electronic devices. The observations of spatial self-phase modulation and the associated multiple diffraction ring patterns in liquid suspensions of 2D nanomaterials are believed to be excellent examples of strong laser interaction with 2D nanomaterials and this phenomenon has been attributed to their large electronic third-order susceptibilities. By performing a series of control experiments with liquid suspensions of graphene and graphene oxide flakes in different solvents at various temperatures under an increasing modulation frequency of laser illumination, we first show that the diffraction ring pattern has little dependence on the type of nanomaterial but strongly depends on the duration of laser illumination. A laser induced local refractive index change is then monitored by a weaker probe beam, resulting in the divergent diffraction of the probe beam that indicates a lower self-induced refractive index in the center of the pump laser beam than at its periphery: a clear signature of the thermal lens effect. Finally, we use computational fluid dynamics to simulate laser induced temperature and index changes of the suspensions. The evolution of diffraction rings is well correlated to the transient temperature distribution. Our understanding of complex laser interactions with nanomaterial suspensions and the associated thermal lens effect paves the way for further basic studies and fluid opto-electronic applications of 2D nanomaterials.

Laser streaming: Turning a laser beam into a flow of liquid.

Transforming a laser beam into a mass flow has been a challenge both scientifically and technologically. We report the discovery of a new optofluidic principle and demonstrate the generation of a steady-state water flow by a pulsed laser beam through a glass window. To generate a flow or stream in the same path as the refracted laser beam in pure water from an arbitrary spot on the window, we first fill a glass cuvette with an aqueous solution of Au nanoparticles. A flow will emerge from the focused laser spot on the window after the laser is turned on for a few to tens of minutes; the flow remains after the colloidal solution is completely replaced by pure water. Microscopically, this transformation is made possible by an underlying plasmonic nanoparticle-decorated cavity, which is self-fabricated on the glass by nanoparticle-assisted laser etching and exhibits size and shape uniquely tailored to the incident beam profile. Hydrophone signals indicate that the flow is driven via acoustic streaming by a long-lasting ultrasound wave that is resonantly generated by the laser and the cavity through the photoacoustic effect. The principle of this light-driven flow via ultrasound, that is, photoacoustic streaming by coupling photoacoustics to acoustic streaming, is general and can be applied to any liquid, opening up new research and applications in optofluidics as well as traditional photoacoustics and acoustic streaming.

Orientation Control of Graphene Flakes by Magnetic Field: Broad Device Applications of Macroscopically Aligned Graphene.

Owing to a large diamagnetism, graphene flakes can respond and be aligned to magnetic field like a ferromagnetic material. Aligned graphene flakes exhibit emergent properties approaching single-layer graphene. Anisotropic optical properties also give rise to a magnetic writing board using graphene suspension and a bar magnet as a pen. This simple alignment technique opens up enormous applications of graphene.

Efficient hydrogen evolution by ternary molybdenum sulfoselenide particles on self-standing porous nickel diselenide foam.

With the massive consumption of fossil fuels and its detrimental impact on the environment, methods of generating clean power are urgent. Hydrogen is an ideal carrier for renewable energy; however, hydrogen generation is inefficient because of the lack of robust catalysts that are substantially cheaper than platinum. Therefore, robust and durable earth-abundant and cost-effective catalysts are desirable for hydrogen generation from water splitting via hydrogen evolution reaction. Here we report an active and durable earth-abundant transition metal dichalcogenide-based hybrid catalyst that exhibits high hydrogen evolution activity approaching the state-of-the-art platinum catalysts, and superior to those of most transition metal dichalcogenides (molybdenum sulfide, cobalt diselenide and so on). Our material is fabricated by growing ternary molybdenum sulfoselenide particles on self-standing porous nickel diselenide foam. This advance provides a different pathway to design cheap, efficient and sizable hydrogen-evolving electrode by simultaneously tuning the number of catalytic edge sites, porosity, heteroatom doping and electrical conductivity.

Graphene oxide liquid crystals for reflective displays without polarizing optics.

The recent emergence of liquid crystals of atomically thin two-dimensional (2D) materials not only has allowed us to explore novel phenomena of macroscopically aligned 2D nanomaterials but also has provided a route toward their controlled assembly into three-dimensional functional macrostructures. Using flow-induced mechanical alignment, we prepared flakes of graphene oxide (GO) in different orientational orders and demonstrated that GO liquid crystals (LC) can be used as rewritable media for reflective displays without polarizing optics. With a wire or stick as a pen, we can make the surface of GO LC reflective and bright, and we can then manually draw lines, curves, and any patterns with dark appearance. The contrast between bright and dark features is due to anisotropic optical responses of ordered GO flakes. Since optical anisotropy is an intrinsic property of 2D structures, our observations and demonstration represent one of many potential applications of macroscopically aligned 2D nanomaterials.

Atomic cobalt on nitrogen-doped graphene for hydrogen generation.

Reduction of water to hydrogen through electrocatalysis holds great promise for clean energy, but its large-scale application relies on the development of inexpensive and efficient catalysts to replace precious platinum catalysts. Here we report an electrocatalyst for hydrogen generation based on very small amounts of cobalt dispersed as individual atoms on nitrogen-doped graphene. This catalyst is robust and highly active in aqueous media with very low overpotentials (30 mV). A variety of analytical techniques and electrochemical measurements suggest that the catalytically active sites are associated with the metal centres coordinated to nitrogen. This unusual atomic constitution of supported metals is suggestive of a new approach to preparing extremely efficient single-atom catalysts.