Search

Metal-based chemoimmunotherapy has recently garnered significant attention for its capacity to stimulate tumor-specific immunity beyond direct cytotoxic effects. Such effects are usually caused by ICD via the activation of DAMP signals. However, metal complexes that can elicit antitumor immune responses other than ICD have not yet been described. Herein, we report that a rhodium complex (Rh-1) triggers potent antitumor immune responses by downregulating Wnt/β-catenin signaling with subsequent activation of T lymphocyte infiltration to the tumor site. The results of mechanistic experiments suggest that ROS accumulation following Rh-1treatment is a critical trigger of a decrease in β-catenin and enhanced secretion of CCL4, a key mediator of T cell infiltration. Through these properties, Rh-1exerts a synergistic effect in combination with PD-1 inhibitors against tumor growth in vivo. Taken together, our work describes a promising metal-based antitumor agent with a noncanonical mode of action to sensitize tumor tissues to ICB therapy.

Oxathiapiprolin (OXA), which targets the oxysterol-binding protein (OSBP), is an outstanding piperidinyl thiazole isoxazoline (PTI) fungicide that can be used to control oomycetes diseases. In this study, starting from the structure of OXA, a series of novel OSBP inhibitors were designed and synthesized by introducing an indole moiety to replace the pyrazole in OXA. Finally, compound b24was found to exhibit the highest control effect (82%) against cucumber downy mildew (CDM) in the greenhouse at a very low dosage of 0.069 mg/L, which was comparable to that of OXA (88%). Furthermore, it showed better activity against potato late blight (PLB) than other derivatives of indole. The computational results showed that the R-conformation of b24should be the dominant conformation binding to PcOSBP. The results of the present work indicate that the 3-fluorine-indole ring is a favorable fragment to increasing the electronic energy when binding with PcOSBP. Furthermore, compound b24could be used as a lead compound for the discovery of new OSBP inhibitors.

Objective The study aimed to investigate the clinical characteristics of patients with multi-canal benign paroxysmal positional vertigo (MC-BPPV).Methods We performed a retrospective analysis of 927 patients with BPPV who were admitted to our hospital between January 1, 2016 and December 31, 2019. The clinical data of all patients were collected. The Dix-Hallpike, straight head-hanging, and supine Roll tests were performed in all patients. The nystagmus was recorded using videonystagmography. The clinical characteristics of patients with MC-BPPV and single canal BPPV (SC-BPPV) was analyzed and compared.Results Among 927 patients included, 49 (5.29%) patients had MC-BPPV, 878 (94.71%) patients had SC-BPPV. There were significant differences in the male to female ratio (1:3.90 vs 1:1.81, P< .05), mean age (62.47±12.51 vs 59.04±13.72, P< .05), as well as the ratio of cupulolithiasis to canalithiasis (1:1.45 vs 1:4.78, P< .01) between patients with MC-BPPV and SC-BPPV. The frequency of involvement of PC, HC, and AC were involved for 66 (67.35%), 23 (23.47%), and 9 (9.18%) times, respectively, in patients with MC-BPPV, which were involved in 581 (66.17%), 281 (32.0%), and 16 (1.82%) patients, respectively, in patients with SC-BPPV. No significant difference was found in the frequency of involvement of PC and HC between patients with MC-BPPV and SC-BPPV, while there was significant difference in the frequency of AC involvement between 2 groups (P< .01). Ipsilateral PC-HC-BPPV (n = 18) and bilateral PC-BPPV (n=19) were the most common among patients with MC-BPPV. Twenty-six (53.06%) patients had ipsilateral MC-BPPV, 23 (46.94%) had bilateral MC-BPPV. Of the 26 patients with ipsilateral MC-BPPV, 7 patients combined with unilateral peripheral vestibular disorder.Conclusion Patients with MC-BPPV had a significantly older mean age at disease onset and a higher proportion of females compared with patients with SC-BPPV. Cupulolithiasis was more common in MC-BPPV. AC involvement was also much more common in MC-BPPV than in SC-BPPV.

Intrauterine adhesion (IUA) is manifestations of endometrial fibrosis and excessive extracellular matrix deposition. C1q/tumor necrosis factor-related protein-6 (CTRP6) is a newly identified adiponectin paralog which has been reported to modulate the fibrosis process of several diseases; however, the endometrial fibrosis function of CTRP6 remains unknown. Our study aimed to assess the role of CTRP6 in endometrial fibrosis and further explore the underlying mechanism. Here, we found that the expression of CTRP6 was downregulated in the endometrial tissues of IUA. In vitro experiments demonstrated the reduced level of CTRP6 in facilitated transforming growth factor-β1 (TGF-β1)-induced human endometrial stromal cells (HESCs). In addition, CTRP6 inhibited the expression of α-smooth muscle actin (α-SMA) and collagen I in TGF-β1-treated HESCs. Mechanistically, CTRP6 activated the AMP-activated protein kinase (AMPK) and protein kinase B (AKT) pathway in HESCs, and AMPK inhibitor (AraA) or PI3K inhibitor (LY294002) pretreatment abolished the protective effect of CTRP6 on TGF-β1-induced fibrosis. CTRP6 markedly decreased TGF-β1-induced Smad3 phosphorylation and nuclear translocation, and AMPK or AKT inhibition reversed these effects. Notably, CTRP6-overexpressing treatment alleviated the fibrosis of endometrium in vivo. Therefore, CTRP6 ameliorates endometrial fibrosis, among which AMPK and AKT are essential for the anti-fibrotic effect of CTRP6 via the Smad3 pathway. Taken together, CTRP6 may be a potential therapeutic target for the treatment of intrauterine adhesion.Graphical Abstract

In this work, we fabricated high-performance GaN-based ultraviolet resonant cavity light-emitting diodes (RCLEDs) with dual dielectric distributed Bragg reflectors (DBRs). The devices were configured a copper plate and AlN current confinement aperture, which improved thermal dissipation and increased the maximum output power density up to 84.03 W/cm2 at injected current density of ~36 kA/cm2. The emission wavelength of the devices is 376.7 nm and narrow cavity modes were observed with a linewidth of 0.24 nm, corresponding to a high quality factor (Q) of 1570.

We consider the problem of complex root classification, i.e., finding the conditions on the coefficients of a univariate polynomial for all possible multiplicity structures on its complex roots. It is well known that such conditions can be written as conjunctions of several polynomial equalities and one inequality in the coefficients. Those polynomials in the coefficients are called discriminants for multiplicities. It is also known that discriminants can be obtained by using repeated parametric gcd’s. The resulting discriminants are usually nested determinants, i.e., determinants of matrices whose entries are determinants, and so on. In this paper, we give a new type of discriminants which are not based on repeated gcd’s. The new discriminants are simpler in the sense that they are non-nested determinants and have smaller maximum degrees.

The dynamic stability is crucial to successful operation and passenger comfort in zero-flux electric-dynamic suspension (EDS) systems. Usually, the stability problem is studied by a dynamic method where equations of motion are solved, with the electromagnetic interaction and the motion of the vehicle coupled in different levels. The dynamic studies provide information on operation strategies such as active or passive damping designs. In this work, the stability of the system is studied from another angle, where the vehicle body and bogie are taken as a whole and the stability is evaluated from the “potential energy surface” of the system. Although the system is not conservative, the difference between path integrals of electromagnetic force along different paths is small. For approximation, the stability is evaluated by taking the path integral as potential energy. Instead of dynamic stabilities, the method reveals the quasi-static stabilities. Instead of a damping strategy, the work is focused on the geometrical design parameters. The study is done with different system design parameters, which reveals that the height of the upper ground coil is one of the most important parameters that affect the lateral-roll coupled stability. The design principle is to have maximum mutual inductance between the on-board and upper ground coils, as well as maximum spatial derivative of the mutual inductance.

Fe-based nanocrystalline materials is a typical soft-magnetic material with advantages such as high saturated magnetic flux, high resistivity and low magnetostriction coefficient. By utilizing a specialized winding process, the ultra-thin strip has been successfully applied for use in scanning magnetic cores. For static field, the simulated and tested integral magnetic field uniformity is consistent, and tested effective length is slightly shorter than simulated one. The static magnetic field can meet the needs of scanning magnets. For transient field, the new iron core has less magnetic field delay and distortion compared to silicon steel sheet iron. The simulated maximum magnetic field delay is reduced from 161 Gauss to 16 Gauss. The maximum magnetic field delay of silicon steel sheet iron under test is 87 Gauss, and the corresponding data of the new iron core is almost 0 Gauss. With the weakening of the magnetic field delay, the magnetic field distortion should also be suppressed. With the novel iron core, the magnetic field of the scanning magnet can be improved, thereby reducing the distance from the scanning magnet to the terminal. Rotating gantry is the focus of current research on proton and heavy ion therapy accelerator facilities. This novel iron core can facilitate a decrease in the rotating diameter and weight of the gantry, while enhancing the scanning accuracy. Moreover, the novel iron core can be exploited in scenarios where ferrite cores are “excess capacity”, but traditional silicon steel cores are “insufficient capacity”, such as for certain bump magnets used in synchrotrons.

The Space Environment Simulation and Research Infrastructure (SESRI), located at the Harbin Institute of Technology (HIT) in China, is a new infrastructure project proposed by the Institute of Modern Physics, Chinese Academy of Sciences (IMP, CAS), and completed in 2022. As a critical part of SESRI, the compact synchrotron was designed with a circumference of less than 44 m and compact magnets. In order to achieve compact injection and improve injection efficiency, four fast-ramping bump magnets based on ferrite yokes were used. All four bump magnets have a fast falling time from 20–100 µs, a maximum magnetic field of 0.0797 T, and a gap of 60 mm. To reduce the magnetic eddy current effect and coil inductance during fast excitation, ferrite core structures with single copper bar saddle windings are used. Further, window-frame structures are used to facilitate the ferrite-core machining process. After the prototype bump magnet was fabricated and the pulsed magnetic field measured, it was found that the integrated magnetic field curve did not align with the output current curve of the power supply. This was found to be caused by eddy currents from the copper gaskets between ferrite cores. Through the simulation and secondary testing of the gasket-induced eddy currents using different materials, the eddy current has been significantly reduced. In this study, the magnetic field optimization, structural design, eddy current calculation, and magnetic field measurement of the fast-ramping bump magnets are analyzed.

As one of the key components of synchrotron injection and extraction system, the coil of the septum is subjected to large electromagnetic force during excitation, resulting in inevitable deformation of the coil, which affects the safe and stable operation of the magnet. Therefore, it is necessary to conduct a detailed analysis of the failure mechanism of the coil during operation. In this paper, an improved septum magnet structure is proposed, which reduced the stress of the coil effectively. Furthermore, a refined model of the septum magnet is established based on finite element method, the electromagnetic field and deformation of the magnet under the operating state are simulated, more fine strain/stress profiles of the copper wire, insulation and epoxy have been obtained. And compared with the traditional homogenized model and measurement results, the results show that the refined model can reflect the mechanical response between the turns of the coils more effectively. According to the results, a septum magnet is developed, which effectively improves and extends the operating stability and service life than previous septum magnet.

• The TiO 2 /Bi 2 S 3 S-scheme heterojunction is prepared by hydrothermal method. • The TiO 2 /Bi 2 S 3 hybrid showed wide spectrum response and good photothermal effect. • An improved CO 2 photoreduction performance was achieved by the hybrid. • DFT calculation and in-situ characterization were used to clarify the mechanism. The combination of S-scheme heterojunction and photothermal effect is a promising strategy to achieve efficient CO 2 photoreduction into solar fuel due to the boosted charge carrier separation efficiency and faster surface reaction rate. Herein, unique photothermal-coupled TiO 2 /Bi 2 S 3 S-scheme heterojunction nanofibers were fabricated and applied to a full-spectrum CO 2 photoreduction system. Density functional theory calculation and experimental analyses have confirmed the generation of the internal electric field and the S-scheme electron transfer pathway, leading to a highly efficient charge carrier separation. Thanks to the excellent photothermal conversion capacity of Bi 2 S 3 , the photogenerated electron transfer rate, and surface reaction rate were further accelerated in hybrid photocatalysts. Under the synergistic effect of S-scheme heterojunction and photothermal effects, the optimal TiO 2 /Bi 2 S 3 nanofibers achieved 7.65 μmol h–1 of CH 4 production rate, which is 5.24 times higher than that of pristine TiO 2. Moreover, the morphology reconstruction of Bi 2 S 3 in hybrids facilitates the CH 4 selectivity was significantly improved from 64.2% to 88.7%. Meanwhile, the CO 2 photoreduction reaction route over TiO 2 /Bi 2 S 3 nanofibers was investigated based on in-situ Fourier transform infrared spectra. This work provides some useful hints for designing highly efficient photothermal-coupled photocatalysts for CO 2 photoreduction. [Display omitted] [ABSTRACT FROM AUTHOR]

Mo K-edge X-ray absorption spectroscopy (XAS) is used to probe the structure of wild-type Campylobacter jejuninitrate reductase NapA and the C176A variant. The results of extended X-ray absorption fine structure (EXAFS) experiments on wtNapA support an oxidized Mo(VI) hexacoordinate active site coordinated by a single terminal oxo donor, four sulfur atoms from two separate pyranopterin dithiolene ligands, and an additional S atom from a conserved cysteine amino acid residue. We found no evidence of a terminal sulfido ligand in wtNapA. EXAFS analysis shows the C176A active site to be a 6-coordinate structure, and this is supported by EPR studies on C176A and small molecule analogs of Mo(V) enzyme forms. The SCysis replaced by a hydroxide or water ligand in C176A, and we find no evidence of a coordinated sulfhydryl (SH) ligand. Kinetic studies show that this variant has completely lost its catalytic activity toward nitrate. Taken together, the results support a critical role for the conserved C176 in catalysis and an oxygen atom transfer mechanism for the catalytic reduction of nitrate to nitrite that does not employ a terminal sulfido ligand in the catalytic cycle.

The polymer materials in nuclear facilities are exposed to high temperatures, radiation, and high loads. Their excellent heat resistance, radiation resistance, and shielding properties are important for the safe operation of nuclear facilities. In this study, 1,2-bis(hydroxymethyl)carborane (CBOH) was first synthesized in large quantities through water extraction and then introduced into an epoxy resin cross-linked network. The incorporation of a carborane structure significantly improved the heat resistance of epoxy. Under air atmosphere, the T5%(the temperature at 5 wt % degradation), T10%(the temperature at 10 wt % degradation), and char yield at 800 °C of the materials were 315.67 °C (16.51 °C increased), 326.29 °C (12.96 °C increased), and 33.22% (33.22% increased), respectively. The maximum decomposition temperature of the material increased from 550 to 750 °C, and 7.05 wt % of the carbon constituent was protected after thermal degradation at 800 °C. The glass transition temperature (Tg) of the materials greatly increased up to over 300 °C after introducing the carborane structure into the networks. The radiation resistance of the material was enhanced due to the in situ capture of oxygen radicals by the carborane structure. Moreover, the incorporation of carborane structure also increased the content of H and B in materials, improving their neutron-shielding capability. This work confers multifunctionality to epoxy resin and enhances its various properties, ensuring the safety of epoxy resin in nuclear facilities.

In this work, methane hydrate formation experiments are conducted under the methane gas–water–silt sand three-phase flow by using a novel flow loop. The experimental results show that the increase in flow velocities and silt sand concentrations both increase the methane hydrate formation rate and the pressure drop of the three-phase fluid. The flow velocity has a stronger effect on hydrate formation rates and pressure drops than the silt sand concentration, but under the same flow velocity condition, the increase in silt sand concentrations amplifies the effect of flow velocity. Moreover, a new interesting observation is found that, during the methane hydrate formation, the pressure drop of the mixture fluid exhibits a nonlinear relationship with experiment time, which has a similar trend to the methane hydrate formation rate vs experiment time. The phenomenon of methane hydrate formation can influence the pressure drop significantly, in that the increase in the hydrate formation rate results in the larger pressure drop. This work provides a theoretical foundation for developing the hydrate management plan for the water-drainage pipe line in a natural gas hydrate production well.

Background and Objectives: A substantial inter-individual variability has been observed in the pharmacokinetics of lamotrigine. The aim of the study was to investigate the impact of genetic polymorphism of the metabolizing enzymes (UGT2B7, UGT1A4) and transporter (ABCG2) on the pharmacokinetics and therapeutic efficacy of lamotrigine in patients with epilepsy. Methods: The genetic analysis of single-nucleotide polymorphisms was conducted using polymerase chain reaction sequence. High-performance liquid chromatography/tandem mass spectrometry was employed to measure the plasma concentrations of lamotrigine. The efficacy of lamotrigine was assessed by evaluating the reduction rate of epileptic seizure frequency. Results: This study included a cohort of 331 patients who were treated with lamotrigine as monotherapy. A linear correlation was observed between the lamotrigine concentration and daily dose taken (r= 0.58, p&lt; 2.2e−16). Statistically significant differences were found in both the median plasma concentration and dose-adjusted concentration (C/D ratio) when comparing the ineffective to the effective group (p&lt; 0.05). Multivariate analysis showed that UGT1A4rs2011425, ABCG2rs2231142 polymorphisms and age had a significant relationship with the lamotrigine concentrations (p&lt; 0.05). Age was a predictive factor for C/D ratio (p&lt; 0.001). Lamotrigine concentration and weight were good predictive factors for effective seizure outcomes (odds ratio [OR] = 0.715, 95% CI 0.658–0.776, p&lt; 0.001; OR = 0.926, 95% CI 0.901–0.951, p&lt; 0.001, respectively). The cut-off values of lamotrigine trough concentrations for clinical outcomes in the age-related groups were determined as 2.49 μg/ml (area under the receiver-operating characteristic curve [AUC]: 0.828, 95% CI 0.690–0.966), 2.70 μg/ml (AUC: 0.805, 95% CI 0.745-0.866) and 3.25 μg/ml (AUC: 0.807, 95% CI 0.686–0.928) for the adult group, adolescent group, and toddler and school-age group, respectively. Conclusions: UGT1A4rs2011425 and ABCG2rs2231142 were correlated with lamotrigine concentrations. Lower lamotrigine trough concentration was found in the ineffective group and the troughs were associated with seizure outcomes.