Drug-drug interaction between tacrolimus and caspofungin in Chinese kidney transplant patients with different CYP3A5 genotypes.

Background: The effect of drug-drug interaction between tacrolimus and caspofungin on the pharmacokinetics of tacrolimus in different CYP3A5 genotypes has not been reported in previous studies. Objectives: To investigate the effect of caspofungin on the blood concentration and dose of tacrolimus under different CYP3A5 genotypes. Design: We conducted a retrospective cohort study in The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital from January 2015 to December 2022. All kidney transplant patients were divided into the combination or non-combination group based on whether tacrolimus was combined with caspofungin or not. Patients were subdivided into CYP3A5 expressers (CYP3A5*1/*1 or CYP3A5*1/*3) and CYP3A5 non-expressers (CYP3A5*3/*3). Methods: Data from the combination and the non-combination groups were matched with propensity scores to reduce confounding by SPSS 22.0. A total of 200 kidney transplant patients receiving tacrolimus combined with caspofungin or not were enrolled in this study. Statistical analysis was conducted on the dose-corrected trough concentrations (C0/D) and dose requirements (D) of tacrolimus using independent sample two-sided t-test and nonparametric tests to investigate the impact on patients with different. Results: In this study, the C0/D values of tacrolimus were not significantly different between the combination and non-combination groups (p = 0.054). For CYP3A5 expressers, there was no significant difference in tacrolimus C0/D or D values between the combination and non-combination groups (p = 0.359; p = 0.851). In CYP3A5 nonexpressers, the C0/D values of tacrolimus were significantly lower in the combination than in the non-combination groups (p = 0.039), and the required daily dose of tacrolimus was increased by 11.11% in the combination group. Conclusion: Co-administration of caspofungin reduced tacrolimus blood levels and elevated the required daily dose of tacrolimus. In CYP3A5 non-expressers, co-administration of caspofungin had a significant effect on tacrolimus C0/D values. An approximate 10% increase in the weight-adjusted daily dose of tacrolimus in CYP3A5 non-expressers is recommended to ensure the safety of tacrolimus administration.

Differential drug interactions of caspofungin on tacrolimus in Chinese kidney transplant patients with different CYP3A5 genotypes Why was the study done? Currently, there have been studies reporting the effect of caspofungin on tacrolimus blood concentrations, but the conclusions are conflicting, and no study has focused on the effect of CYP3A5 genotypes on the drug-drug interaction. We explored a number of research questions: 1. Does caspofungin have an effect on the pharmacokinetics of the immunosuppressant tacrolimus? 2. How does CYP3A5*3, which affects tacrolimus metabolism significantly, affect tacrolimus blood concentration levels? 3. How should the dose of tacrolimus be adjusted when combined with caspofungin? What did the researchers do? By reviewing literature, we understood the problems related with the kidney transplant patients better, which led to the development of strict inclusion and exclusion criteria. The patients (from January 2015 to December 2022) were categorized into combination and non-combination groups according to whether they were co-administered with caspofungin or not. The results of the study were analyzed using SPSS 22.0. What did the researchers find? The study finally included 200 patients. We found no statistically significant differences in the dose-corrected trough concentrations (C₀/D) and dose requirements (D) of tacrolimus between the combination and non-combination groups. However, in patients with CYPA5*3/*3 genotype, tacrolimus C₀/D values were significantly lower in the combination group than in the non-combination group, and the required daily tacrolimus dose was increased. What do the findings mean? This study has found that co-administration of caspofungin in patients with CYP3A5*3/*3 genotype resulted in a significant decrease in the C₀/D value of tacrolimus, therefore, an appropriate increase in the daily dose of tacrolimus is recommended. The implication is that it is important and necessary to monitor the concentrations of tacrolimus and the CYP3A5 genotypes, and adjust the dose when combined or discontinuing with caspofungin in kidney transplant patients.

Deinococcus wulumuqiensis R12 synthesized silver nanoparticles with peroxidase-like activity for synergistic antibacterial application.

The use of a combination of several antibacterial agents for therapy holds great promise in reducing the dosage and side effects of these agents, improving their efficiency, and inducing potential synergistic therapeutic effects. Herein, this study provides an innovative antibacterial treatment strategy by synergistically combining R12-AgNPs with H2O2 therapy. R12-AgNPs were simply produced with the supernatant of an ionizing radiation-tolerant bacterium Deinococcus wulumuqiensis R12 by one-step under room temperature. In comparison with chemically synthesized AgNPs, the biosynthesized AgNPs presented fascinating antibacterial activity and peroxidase-like properties, which endowed it with the capability to catalyze the decomposition of H2O2 to generate hydroxyl radical. After the combination of R12-AgNPs and H2O2, an excellent synergistic bacteriostatic activity was observed for both Escherichia coli and Staphylococcus aureus, especially at low concentrations. In addition, in vitro cytotoxicity tests showed R12-AgNPs had good biocompatibility. Thus, this work presents a novel antibacterial agent that exhibits favorable synergistic antibacterial activity and low toxicity, without the use of antibiotics or a complicated synthesis process.

Evidence of the fractional quantum spin Hall effect in moiré MoTe2.

Quantum spin Hall (QSH) insulators are two-dimensional electronic materials that have a bulk band gap similar to an ordinary insulator but have topologically protected pairs of edge modes of opposite chiralities1-6. So far, experimental studies have found only integer QSH insulators with counter-propagating up-spins and down-spins at each edge leading to a quantized conductance G0 = e2/h (with e and h denoting the electron charge and Planck's constant, respectively)7-14. Here we report transport evidence of a fractional QSH insulator in 2.1° twisted bilayer MoTe2, which supports spin-Sz conservation and flat spin-contrasting Chern bands15,16. At filling factor ν = 3 of the moiré valence bands, each edge contributes a conductance 3 2 G 0 with zero anomalous Hall conductivity. The state is probably a time-reversal pair of the even-denominator 3/2-fractional Chern insulators. Furthermore, at ν = 2, 4 and 6, we observe a single, double and triple QSH insulator with each edge contributing a conductance G0, 2G0 and 3G0, respectively. Our results open up the possibility of realizing time-reversal symmetric non-abelian anyons and other unexpected topological phases in highly tunable moiré materials17-19.

Contribution of platelets to disruption of the blood-brain barrier during arterial baroreflex dysfunction.

BACKGROUND: Arterial baroreflex dysfunction, like many other central nervous system disorders, involves disruption of the blood-brain barrier, but what causes such disruption in ABR dysfunction is unclear. Here we explored the potential role of platelets in this disruption. METHODS: ABR dysfunction was induced in rats using sinoaortic denervation, and the effects on integrity of the blood-brain barrier were explored based on leakage of Evans blue or FITC-dextran, while the effects on expression of CD40L in platelets and of key proteins in microvascular endothelial cells were explored using immunohistochemistry, western blotting and enzyme-linked immunosorbent assay. Similar experiments were carried out in rat brain microvascular endothelial cell line, which we exposed to platelets taken from rats with ABR dysfunction. RESULTS: Sinoaortic denervation permeabilized the blood-brain barrier and downregulated zonula occludens-1 and occludin in rat brain, while upregulating expression of CD40L on the surface of platelets and stimulating platelet aggregation. Similar effects of permeabilization and downregulation were observed in healthy rats that received platelets from animals with ABR dysfunction, and in rat brain microvascular endothelial cells, but only in the presence of lipopolysaccharide. These effects were associated with activation of NF-κB signaling and upregulation of matrix metalloprotease-9. These effects of platelets from animals with ABR dysfunction were partially blocked by neutralizing antibody against CD40L or the platelet inhibitor clopidogrel. CONCLUSION: During ABR dysfunction, platelets may disrupt the blood-brain barrier when CD40L on their surface activates NF-kB signaling within cerebral microvascular endothelial cells, leading to upregulation of matrix metalloprotease-9. Our findings imply that targeting CD40L may be effective against cerebral diseases involving ABR dysfunction.

The 15-min (Sub)Cellular Proteome.

Single-cell mass spectrometry (MS) opens a proteomic window onto the inner workings of cells. Here, we report the discovery characterization of the subcellular proteome of single, identified embryonic cells in record speed and molecular coverage. We integrated subcellular capillary microsampling, fast capillary electrophoresis (CE), high-efficiency nano-flow electrospray ionization, and orbitrap tandem MS. In proof-of-principle tests, we found shorter separation times to hinder proteome detection using DDA, but not DIA. Within a 15-min effective separation window, CE data-independent acquisition (DIA) was able to identify 1,161 proteins from single HeLa-cell-equivalent (∼200 pg) proteome digests vs. 401 proteins by the reference data-dependent acquisition (DDA) on the same platform. The approach measured 1,242 proteins from subcellular niches in an identified cell in the live Xenopus laevis (frog) embryo, including many canonical components of organelles. CE-MS with DIA enables fast, sensitive, and deep profiling of the (sub)cellular proteome, expanding the bioanalytical toolbox of cell biology. Authorship Contributions: P.N. and B.S. designed the study. L.R.P. collected the X. laevis cell aspirates. B.S. prepared and measured the samples. B.S. and P.N. analyzed the data and interpreted the results. P.N. and B.S. wrote the manuscript. All the authors commented on the manuscript.

Giant spin Hall effect in AB-stacked MoTe2/WSe2 bilayers.

The spin Hall effect (SHE), in which an electrical current generates a transverse spin current, plays an important role in spintronics for the generation and manipulation of spin-polarized electrons. The phenomenon originates from spin-orbit coupling. In general, stronger spin-orbit coupling favours larger SHEs but shorter spin relaxation times and diffusion lengths. However, correlated magnetic materials often do not support large SHEs. Achieving large SHEs, long-range spin transport and magnetism simultaneously in a single material is attractive for spintronics applications but has remained a challenge. Here we demonstrate a giant intrinsic SHE coexisting with ferromagnetism in AB-stacked MoTe2/WSe2 moiré bilayers by direct magneto-optical imaging. Under moderate electrical currents with density <1 A m-1, we observe spin accumulation on transverse sample edges that nearly saturates the spin density. We also demonstrate long-range spin Hall transport and efficient non-local spin accumulation that is limited only by the device size (about 10 µm). The gate dependence shows that the giant SHE occurs only near the interaction-driven Chern insulating state. At low temperatures, it emerges after the quantum anomalous Hall breakdown. Our results demonstrate moiré engineering of Berry curvature and electronic correlation for potential spintronics applications.

Radiomic signatures reveal multiscale intratumor heterogeneity associated with tissue tolerance and survival in re-irradiated nasopharyngeal carcinoma: a multicenter study.

BACKGROUND: Post-radiation nasopharyngeal necrosis (PRNN) is a severe adverse event following re-radiotherapy for patients with locally recurrent nasopharyngeal carcinoma (LRNPC) and associated with decreased survival. Biological heterogeneity in recurrent tumors contributes to the different risks of PRNN. Radiomics can be used to mine high-throughput non-invasive image features to predict clinical outcomes and capture underlying biological functions. We aimed to develop a radiogenomic signature for the pre-treatment prediction of PRNN to guide re-radiotherapy in patients with LRNPC. METHODS: This multicenter study included 761 re-irradiated patients with LRNPC at four centers in NPC endemic area and divided them into training, internal validation, and external validation cohorts. We built a machine learning (random forest) radiomic signature based on the pre-treatment multiparametric magnetic resonance images for predicting PRNN following re-radiotherapy. We comprehensively assessed the performance of the radiomic signature. Transcriptomic sequencing and gene set enrichment analyses were conducted to identify the associated biological processes. RESULTS: The radiomic signature showed discrimination of 1-year PRNN in the training, internal validation, and external validation cohorts (area under the curve (AUC) 0.713-0.756). Stratified by a cutoff score of 0.735, patients with high-risk signature had higher incidences of PRNN than patients with low-risk signature (1-year PRNN rates 42.2-62.5% vs. 16.3-18.8%, P < 0.001). The signature significantly outperformed the clinical model (P < 0.05) and was generalizable across different centers, imaging parameters, and patient subgroups. The radiomic signature had prognostic value concerning its correlation with PRNN-related deaths (hazard ratio (HR) 3.07-6.75, P < 0.001) and all causes of deaths (HR 1.53-2.30, P < 0.01). Radiogenomics analyses revealed associations between the radiomic signature and signaling pathways involved in tissue fibrosis and vascularity. CONCLUSIONS: We present a radiomic signature for the individualized risk assessment of PRNN following re-radiotherapy, which may serve as a noninvasive radio-biomarker of radiation injury-associated processes and a useful clinical tool to personalize treatment recommendations for patients with LANPC.

Advanced Etching Techniques of LiNbO3 Nanodevices.

Single LiNbO3 (LNO) crystals are widely utilized in surface acoustic wave devices, optoelectronic devices, and novel ferroelectric memory devices due to their remarkable electro-optic and piezoelectric properties, and high saturation and remnant polarizations. However, challenges remain regarding their nanofabrication that hinder their applications. The prevailing etching techniques for LNO encompass dry etching, wet etching, and focused-ion-beam etching, each having distinct merits and demerits. Achieving higher etching rates and improved sidewall angles presents a challenge in LNO nanofabrication. Building upon the current etching researches, this study explores various etching methods using instruments capable of generating diverse plasma densities, such as dry etching in reactive ion etching (RIE) and inductively coupled plasma (ICP), proton exchange-enhanced etching, and wet chemical etching following high-temperature reduction treatment, as well as hybrid dry and wet etching. Ultimately, after employing RIE dry etching combined with wet etching, following a high-temperature reduction treatment, an etching rate of 10 nm/min and pretty 90° sidewall angles were achieved. Furthermore, high etching rates of 79 nm/min with steep sidewall angles of 83° were obtained using ICP dry etching. Additionally, using SiO2 masks, a high etching rate of 108 nm/min and an etching selectivity ratio of 0.86:1 were achieved. Distinct etching conditions yielded diverse yet exceptional results, providing multiple processing paths of etching for the versatile application of LNO.

Hybrid Dry and Wet Etching of LiNbO3 Domain-Wall Memory Devices with 90° Etching Angles and Excellent Electrical Properties.

Ferroelectric domain walls, agile nanoscale interfaces of polar order, can be selectively controlled by electric fields for their position, conformation, and function, which is ultimately the key to realizing novel low-energy memory and computing structures. LiNbO3 single-crystal domain wall memory has the advantages of high operational speed, high integration density, and virtually unlimited endurance cycles, appearing as a good solution for the next generation of highly miniaturized low-energy memories. However, the etching process poses significant challenges in the nanofabrication and high-density integration of LiNbO3 domain-wall memories. Here, we employed a hybrid etching technique to achieve smooth sidewalls with a 90° inclined angle, leading to a 24% reduction in the coercive field and a 2.5-fold increase in the linear domain wall current density with a retention time of more than 106 seconds and endurance of over 105 writing cycles. Combined with the results of X-ray diffraction patterns and X-ray photoelectric spectra, it is concluded that the excellent electrical performance is related to the formation of an oxygen-deficient LiNbO3-x layer on the sidewall surface during the wet chemical etching process, which is a conductive layer that reduces the thickness of the "dead" layer between the side electrodes and the LiNbO3 cell and rectifies the diode-like wall currents with an onset voltage reduced from 1.23 to 0.28 V. These results prove the high-density integration of ferroelectric domain-wall memories at the nanoscale and provide a new strategy applicable to the development of LiNbO3 photonic devices.

Detection and treatment of biofilm-induced periodontitis by histidine-doped FeSN nanozyme with ultra-high peroxidase-like activity.

Pathogenic biofilm induced oral diseases have posed a significant treat to human health, such as periodontitis resulting from the formation of bacterial biofilm on teeth and gums. The traditional treatment methods such as mechanical debridement and antibiotic therapy encounter the poor therapeutic effect. Recently, numerous nanozymes with excellent antibacterial effect have been widely used in the treatment of oral diseases. In this study, a novel iron-based nanozyme (FeSN) generated by histidine-doped FeS2 with high peroxidase-like (POD-like) activity was designed for the oral biofilm removal and treatment of periodontitis. FeSN exhibited an extremely high POD-like activity, and enzymatic reaction kinetics and theoretical calculations had demonstrated its catalytic efficiency to be approximately 30 times than that of FeS2. The antibacterial experiments showed that FeSN had robust antibacterial activity against Fusobacterium nucleatum in the presence of H2O2, causing a reduction in the levels of glutathione reductase and ATP in bacterial cells, while increasing the level of oxidase coenzyme. The ultrahigh POD-like activity of FeSN allowed for easy detection of pathogenic biofilms and promoted the breakdown of biofilm structure. Furthermore, FeSN demonstrated excellent biocompatibility and low cytotoxicity to human fibroblast cells. In a rat model of periodontitis, FeSN exhibited significant therapeutic effects by reducing the extent of biofilm formation, inflammation, and alveolar bone loss. Taken together, our results suggested that FeSN, generated by self-assembly of two amino acids, represented a promising approach for biofilm removal and periodontitis treatment. This method has the potential to overcome the limitations of current treatments and provide an effective alternative for periodontitis treatment.

Association between GLP-1R gene polymorphism and dyslipidemia in Chinese patients with type 2 diabetes mellitus: A case-control study.

OBJECTIVE: To evaluate the relationship between GLP-1R gene polymorphisms and type 2 diabetes mellitus with dyslipidemia and without dyslipidemia in China. METHODS: A total of 200 patients with Type 2 Diabetes Mellitus (T2DM) were included in this study, including 115 with dyslipidemia and 85 without dyslipidemia. We used Sanger double deoxygenation terminal assay and PCR-RFLP to detect genotype of the GLP-1R rs10305420 and rs3765467 loci. T-test was used to analyze the association between gene polymorphisms and lipid indicators. SHEsis online analysis software was used to analyze the linkage balance effect of loci, and SPSS 26 was used to calculate the gene interaction by dominant model. RESULTS: The genotype distribution of the two loci in the sample of this study was in accordance with Hardy-weinberg equilibrium. There were significant differences in the genotype distribution and allele frequency of rs3765467 between T2DM patients with and without dyslipidemia (GG 52.9%, GA + AA 47.1% vs. GG 69.6%, GA + AA 30.4%; P = 0.017). Under the dominant model, the effects of rs3765467 A allele and rs10305420 T allele on dyslipidemia had multiplicative interactions (P = 0.016) and additive interactions (RERI = 0.403, 95% CI [-2.708 to 3.514]; AP = 0.376, 95% CI [-2.041, 2.793]). Meanwhile, HbA1c levels in rs3765467 A allele carriers (GA + AA) were found to be significantly lower than those in patients with GG genotype (P = 0.006). CONCLUSION: The rs3765467 (G/A) variant is associated with the incidence of dyslipidemia, and G allele may be a risk factor for dyslipidemia.

A KdV-SIR equation and its analytical solutions: An application for COVID-19 data analysis.

To describe the time evolution of infected persons associated with an epidemic wave, we recently derived the KdV-SIR equation that is mathematically identical to the Kortewegde Vries (KdV) equation in the traveling wave coordinate and that represents the classical SIR model under a weakly nonlinear assumption. This study further discusses the feasibility of applying the KdV-SIR equation and its analytical solutions together with COVID-19 data in order to estimate a peak time for a maximum number of infected persons. To propose a prediction method and to verify its performance, three types of data were generated based on COVID-19 raw data, using the following procedures: (1) a curve fitting package, (2) the empirical mode decomposition (EMD) method, and (3) the 28-day running mean method. Using the produced data and our derived formulas for ensemble forecasts, we determined various estimates for growth rates, providing outcomes for possible peak times. Compared to other methods, our method mainly relies on one parameter, σo (i.e., a time independent growth rate), which represents the collective impact of a transmission rate (ß) and a recovery rate (ν). Utilizing an energy equation that describes the relationship between the time dependent and independent growth rates, our method offers a straightforward alternative for estimating peak times in ensemble predictions.

Potential for efficient microbial remediation of Cr(VI) in wastewater using Deinococcus wulumuqiensis R12.

AIMS: This study aimed to investigate the potential of Deinococcus wulumuqiensis R12 (D. wulumuqiensis R12) as a bioadsorbent for Cr(VI) removal from aqueous solutions. METHODS AND RESULTS: Effects of various factors, including initial concentration of Cr(Ⅵ), pH, adsorbent dosage, and time were explored. The maximal Cr removal efficiency was achieved by adding D. wulumuqiensis R12 to the solution at pH 7.0 for 24 h, with an initial Cr concentration of 7 mg l-1. Characterization of bacterial cells showed that Cr was adsorbed to the surface of D. wulumuqiensis R12 by combining with functional groups, such as carboxyl and amino groups on the surface. Furthermore, D. wulumuqiensis R12 was able to keep its bioactivity in the presence of Cr and tolerate Cr concentrations as high as 60 mg l-1. CONCLUSIONS: Deinococcus wulumuqiensis R12 demonstrates a comparatively high adsorption capacity for Cr(VI). Under the optimized conditions, the removal ratio reached 96.4% with 7 mg l-1 Cr(VI), and the maximal biosorption capacity was 2.65 mg g-1. More importantly, it was found that D. wulumuqiensis R12 still had strong metabolic activity and maintained its viability after adsorbing Cr(VI), which is beneficial for biosorbent stability and reuse.

Erasable Domain Wall Current-Dominated Resistive Switching in BiFeO3 Devices with an Oxide-Metal Interface.

Electric transport in the charged domain wall (CDW) region has emerged as a promising phenomenon for the development of next-generation ferro-resistive memory with ultrahigh data storage density. However, accurately measuring the conductivity of CDWs induced by polarization reversal remains challenging due to the polarization modulation of the Schottky barrier at the thin film-electrode interface, which could partially contribute to the collected "on" current of the device. Here, we propose carefully selecting an electrode that can suppress the effect of interfacial barrier modulation induced by polarization reversal, allowing the collected current mainly from the conductive CDWs. The experiment was conducted on epitaxial BiFeO3(001) thin-film devices with vertical and horizontal geometries. Piezo-response force microscopy scanning showed the local polarization experienced 180° rotation to form CDWs under the vertical electric field. However, devices with SrRuO3 epitaxial top electrodes still exhibit an interfacial barrier-dominated diode behavior, with the "on" current proportional to the electrode area. To identify the CDW current, more interfacial defects were introduced by the deposition of Pt top electrodes, which significantly enhanced charge injection for the compensation of the reversed polarization driven by the electric field, leading to the suppressed polarization modulation of the Schottky barrier height. It was observed that the current flow through Pt electrodes is significantly lower compared to that of SRO electrodes and appears to be primarily influenced by the electrode perimeter instead of the electrode area, indicating CDW-dominated conduction behavior in these devices. Planar nanodevices were further fabricated to support the quantitative investigation of the Pt electrode size-dependent "on" current with a linear fit of the current magnitude versus the CDW cross-sectional area. This work constitutes an essential part of understanding the role of the CDW current in ferro-resistive memory devices.

A Lightweight Authentication and Key Agreement Protocol for IoT-Enabled Smart Grid System.

The IoT-enabled Smart Grid uses IoT smart devices to collect the private electricity data of consumers and send it to service providers over the public network, which leads to some new security problems. To ensure the communication security in a smart grid, many researches are focusing on using authentication and key agreement protocols to protect against cyber attacks. Unfortunately, most of them are vulnerable to various attacks. In this paper, we analyze the security of an existent protocol by introducing an insider attacker, and show that their scheme cannot guarantee the claimed security requirements under their adversary model. Then, we present an improved lightweight authentication and key agreement protocol, which aims to enhance the security of IoT-enabled smart grid systems. Furthermore, we proved the security of the scheme under the real-or-random oracle model. The result shown that the improved scheme is secure in the presence of both internal attackers and external attackers. Compared with the original protocol, the new protocol is more secure, while keeping the same computation efficiency. Both of them are 0.0552 ms. The communication of the new protocol is 236 bytes, which is acceptable in smart grids. In other words, with similar communication and computation cost, we proposed a more secure protocol for smart grids.

Spontaneous Chirality Induction in the Assembly of a Single Layer 2D Network with Switchable Pores.

Although two-dimensional (2D) chiral sheet structures are attractive because of their unique chemical and physical properties, single layer 2D chiral network structures with switchable pore interior remain elusive. Here we report spontaneous chirality induction in a single layer 2D network structure formed from the self-assembly of tetrapod azobenzene molecules. The chirality induction arises from multiple sublayers slipped in a preferred direction in which the sublayer consists of unidentical molecular arrangements in the in-plane a and b directions, breaking both the plane of symmetry and inversion symmetry. The protruded azobenzene units in the pore interior can be selectively isomerized upon UV irradiation, resulting in a reversible deformation of the chiral pores while maintaining the 2D frameworks. The chiral network can thus selectively entrap one enantiomer from a racemic solution with near perfect enantioselectivity, and then release it upon UV irradiation.

Gate-tunable heavy fermions in a moiré Kondo lattice.

The Kondo lattice-a matrix of local magnetic moments coupled through spin-exchange interactions to itinerant conduction electrons-is a prototype of strongly correlated quantum matter1-4. Usually, Kondo lattices are realized in intermetallic compounds containing lanthanide or actinide1,2. The complex electronic structure and limited tunability of both the electron density and exchange interactions in these bulk materials pose considerable challenges to studying Kondo lattice physics. Here we report the realization of a synthetic Kondo lattice in AB-stacked MoTe2/WSe2 moiré bilayers, in which the MoTe2 layer is tuned to a Mott insulating state, supporting a triangular moiré lattice of local moments, and the WSe2 layer is doped with itinerant conduction carriers. We observe heavy fermions with a large Fermi surface below the Kondo temperature. We also observe the destruction of the heavy fermions by an external magnetic field with an abrupt decrease in the Fermi surface size and quasi-particle mass. We further demonstrate widely and continuously gate-tunable Kondo temperatures through either the itinerant carrier density or the Kondo interaction. Our study opens the possibility of in situ access to the phase diagram of the Kondo lattice with exotic quantum criticalities in a single device based on semiconductor moiré materials2-9.

Dual-Enzyme Cascade Composed of Chitosan Coated FeS2 Nanozyme and Glucose Oxidase for Sensitive Glucose Detection.

Immobilizing enzymes with nanozymes to catalyze cascade reactions overcomes many of the shortcomings of biological enzymes in industrial manufacturing. In the study, glucose oxidases were covalently bound to FeS2 nanozymes as immobilization carriers while chitosan encapsulation increased the activity and stability of the immobilized enzymes. The immobilized enzymes exhibited a 10% greater increase in catalytic efficiency than the free enzymes while also being more stable and catalytically active in environments with an alkaline pH of 9.0 and a high temperature of 100 °C. Additionally, the FeS2 nanozyme-driven double-enzyme cascade reaction showed high glucose selectivity, even in the presence of lactose, dopamine, and uric acid, with a limit of detection (LOD) (S/N = 3) as low as 1.9 × 10-6 M. This research demonstrates that nanozymes may be employed as ideal carriers for biological enzymes and that the nanozymes can catalyze cascade reactions together with natural enzymes, offering new insights into interactions between natural and synthetic biosystems.

Arterial Baroreflex Dysfunction Promotes Neuroinflammation by Activating the Platelet CD40L/Nuclear Factor Kappa B Signaling Pathway in Microglia and Astrocytes.

Arterial baroreflex (ABR) dysfunction has previously been associated with neuroinflammation, the most common pathological feature of neurological disorders. However, the mechanisms mediating ABR dysfunction-induced neuroinflammation are not fully understood. In the present study, we investigated the role of platelet CD40 ligand (CD40L) in neuroinflammation in an in vivo model of ABR dysfunction, and microglia and astrocyte activation in vitro. ABR dysfunction was induced in Sprague‒Dawley rats by sinoaortic denervation (SAD). We used ELSA and immunofluorescence to assess the effect of platelet CD40L on glial cell polarization and the secretion of inflammatory factors. By flow cytometry, we found that rats subjected to SAD showed a high level of platelet microaggregation and upregulation of CD40L on the platelet surface. The promotion of platelet invasion and accumulation was also observed in the brain tissues of rats subjected to SAD. In the animal model and cultured N9 microglia/C6 astrocytoma cells, platelet CD40L overexpression promoted neuroinflammation and activated M1 microglia, A1 astrocytes, and the nuclear factor kappa B (NFκB) signaling pathway. These effects were partially blocked by inhibiting platelet activity with clopidogrel or inhibiting CD40L-mediated signaling. Our results suggest that during ABR dysfunction, CD40L signaling in platelets converts microglia to the M1 phenotype and astrocytes to the A1 phenotype, activating NFκB and resulting in neuroinflammation. Thus, our study provides a novel understanding of the pathogenesis of ABR dysfunction-induced neuroinflammation and indicates that targeting platelet CD40L is beneficial for treating central nervous system (CNS) disorders associated with ABR dysfunction.