Arsenite-Induced Drug-Drug Interactions in Rats.

Arsenite is an important heavy metal. Some Chinese traditional medicines contain significant amounts of arsenite. The aim of this study was to investigate subacute exposure of arsenite on activities of cytochrome P450 enzymes and pharmacokinetic behaviors of drugs in rats. Midazolam, tolbutamide, metoprolol, omeprazole, caffeine, and chlorzoxazone, the probe substrates for cytochrome P450 (CYP) s3A, 2C6, 2D, 2C11, 1A, and 2E, were selected as probe drugs for the pharmacokinetic study. Significant decreases in areas under the curves of probe substrates were observed in rats after consecutive 30-day exposure to As at 12 mg/kg. Microsomal incubation study showed that the subacute exposure to arsenite resulted in little change in effects on the activities of P450 enzymes examined. However, everted gut sac study demonstrated that such exposure induced significant decreases in intestinal absorption of these drugs by both passive diffusion and carrier-mediated transport. In addition, in vivo study showed that the arsenite exposure decreased the rate of peristaltic propulsion. The decreases in intestinal permeability of the probe drugs and peristaltic propulsion rate most likely resulted in the observed decreases in the internal exposure of the probe drugs. Exposure to arsenite may lead to the reduction of the efficiencies of pharmaceutical agents coadministered resulting from the observed drug-drug interactions. SIGNIFICANCE STATEMENT: Exposure to arsenite may lead to the reduction of the efficiencies of pharmaceutical agents coadministered resulting from the observed drug-drug interactions. The present study, we found that P450 enzyme probe drug exposure was reduced in arsenic-exposed animals (areas under the curve) and the intestinal absorption of the drug was reduced in the animals. Subacute arsenic exposure tends to cause damage to intestinal function, which leads to reduced drug absorption.

Dihydrotanshinone I-Induced CYP1 Enzyme Inhibition and Alteration of Estradiol Metabolism.

Dihydrotanshinone I (DHTI) is a pharmacologically active component occurring in the roots of the herbal medicine Salvia miltiorrhiza Bunge. This study investigated DHTI-induced inhibition of CYP1A1, CYP1A2, and CYP1B1 with the aim to determine the potential effects of DHTI on the bioactivation of estradiol (E2), possibly related to preventive/therapeutic strategy for E2-associated breast cancer. Ethoxyresorufin as a specific substrate for CYP1s was incubated with human recombinant CYP1A1, CYP1A2, or CYP1B1 in the presence of DHTI at various concentrations. Enzymatic inhibition and kinetic behaviors were examined by monitoring the formation of the corresponding product. Molecular docking was further conducted to define the interactions between DHTI and the three CYP1s. The same method and procedure were employed to examine the DHTI-induced alteration of E2 metabolism. DHTI showed significant inhibition of ethoxyresorufin O-deethylation activity catalyzed by CYP1A1, CYP1A2 and CYP1B1 in a concentration-dependent manner (IC50 = 0.56, 0.44, and 0.11 µM, respectively). Kinetic analysis showed that DHTI acted as a competitive type of inhibitor of CYP1A1 and CYP1B1, whereas it noncompetitively inhibited CYP1A2. The observed enzyme inhibition was independent of NADPH and time. Molecular docking analysis revealed hydrogen bonding interactions between DHTI and Asp-326 of CYP1B1. Moreover, DHTI displayed preferential activity to inhibit 4-hydroxylation of E2 (a genotoxic pathway) mediated by CYP1B1. Exposure to DHTI could reduce the risk of genotoxicity induced by E2. SIGNIFICANCE STATEMENT: CYP1A1, CYP1A2, and CYP1B1 enzymes are involved in the conversion of estradiol (E2) into 2-hydroxyestradiol (2-OHE2) and 4-hydroxyestradiol (4-OHE2) through oxidation. 2-OHE2 is negatively correlated with breast cancer risk, and 4-OHE2 may be a significant initiator and promoter of breast cancer. The present study revealed that dihydrotanshinone I (DHTI) competitively inhibits CYP1A1/CYP1B1 and noncompetitively inhibits CYP1A2. DHTI exhibits a preference for inhibiting the genotoxicity associated with E2 4-hydroxylation pathway mediated by CYP1B1, potentially reducing the risk of 4-OHE2-induced genotoxicity.

Kerr soliton frequency comb generation by tuning the coupling coefficient in coupled nonlinear microcavities.

Kerr soliton frequency comb generation in nonlinear microcavities with compact configurations are promising on-chip sources. Current Kerr comb generation by using a single microcavity with a tunable CW pump laser or high-power femtosecond pulse pump are difficult to be integrated on chip. In this paper, we propose an on-chip soliton comb generation scheme by tuning the coupling coefficient of two coupled microcavities instead of tuning the wavelength of the cw pump laser or using a pulsed pump laser in a single microcavity. The two microcavities are assumed to be identical. We showed by numerical simulation that Kerr comb generation is possible in both the blue and red detuned regions of the main microcavity in the coupled cavity system. We further found that the range and boundary of the soliton generation region of the couple microcavities depend on the coupling coefficient between the coupled cavities. To ensure that the modes being coupled have identical optical paths, we designed a Sagnac loop structure which couples the clockwise and counterclockwise modes in a single microcavity and demonstrated Kerr comb generation in both the blue and red detuned regions by tuning the coupling coefficient. The proposed Kerr comb generation scheme can be utilized for chip-scale integrated soliton comb sources, which will contribute to the development of on-chip applications.

Mechanistic Study of Xanthotoxin-Mediated Inactivation of CYP1A2 and Related Drug-Drug Interaction with Tacrine.

Xanthotoxin (XTT) is a biologically active furanocoumarin widely present in foods and plants. The present study is designed to systematically investigate the enzymatic interaction of XTT with CYP1A2, along with pharmacokinetic alteration of tacrine resulting from the co-administration of XTT. The results showed that XTT induced a time-, concentration-, and NADPH-dependent inhibition of CYP1A2, and the inhibition was irreversible. Co-incubation of glutathione (GSH) and catalase/superoxide dismutase was unable to prevent enzyme inactivation. Nevertheless, competitive inhibitor fluvoxamine exhibited a concentration-dependent protective effect against the XTT-induced CYP1A2 inactivation. A GSH trapping experiment provided strong evidence for the production of epoxide or/and γ-ketoenal intermediates resulting from the metabolic activation of XTT. Furthermore, pretreatment of rats with XTT was found to significantly increase the Cmax and area under the curve of plasma tacrine relative to those of tacrine administration alone.

Progressive Classifier Mechanism for Bridge Expansion Joint Health Status Monitoring System Based on Acoustic Sensors.

The application of IoT (Internet of Things) technology to the health monitoring of expansion joints is of great importance in enhancing the efficiency of bridge expansion joint maintenance. In this study, a low-power, high-efficiency, end-to-cloud coordinated monitoring system analyzes acoustic signals to identify faults in bridge expansion joints. To address the issue of scarce authentic data related to bridge expansion joint failures, an expansion joint damage simulation data collection platform is established for well-annotated datasets. Based on this, a progressive two-level classifier mechanism is proposed, combining template matching based on AMPD (Automatic Peak Detection) and deep learning algorithms based on VMD (Variational Mode Decomposition), denoising, and utilizing edge and cloud computing power efficiently. The simulation-based datasets were used to test the two-level algorithm, with the first-level edge-end template matching algorithm achieving fault detection rates of 93.3% and the second-level cloud-based deep learning algorithm achieving classification accuracy of 98.4%. The proposed system in this paper has demonstrated efficient performance in monitoring the health of expansion joints, according to the aforementioned results.

IntEnzyDB: an Integrated Structure-Kinetics Enzymology Database.

Data-driven modeling has emerged as a new paradigm for biocatalyst design and discovery. Biocatalytic databases that integrate enzyme structure and function data are in urgent need. Here we describe IntEnzyDB as an integrated structure-kinetics database for facile statistical modeling and machine learning. IntEnzyDB employs a relational database architecture with a flattened data structure, which allows rapid data operation. This architecture also makes it easy for IntEnzyDB to incorporate more types of enzyme function data. IntEnzyDB contains enzyme kinetics and structure data from six enzyme commission classes. Using 1050 enzyme structure-kinetics pairs, we investigated the efficiency-perturbing propensities of mutations that are close or distal to the active site. The statistical results show that efficiency-enhancing mutations are globally encoded and that deleterious mutations are much more likely to occur in close mutations than in distal mutations. Finally, we describe a web interface that allows public users to access enzymology data stored in IntEnzyDB. IntEnzyDB will provide a computational facility for data-driven modeling in biocatalysis and molecular evolution.

400 MHz ultrafast optical coherence tomography.

An ultrafast time-stretched swept source with a sweep rate of 400 MHz is demonstrated based on the buffering of a 100 MHz femtosecond laser pulse train. To the best of our knowledge, this is the highest sweep rate of swept sources for optical coherence tomography (OCT) that has been reported. With a 10 dB sweep range of ∼100nm, an axial resolution of 19 µm is obtained in the OCT. OCT imaging of high-speed rotating disks is demonstrated. A composite complex apodization method is proposed and demonstrated to enhance the signal to noise ratio in the OCT imaging.

A numerical study of droplet dynamic behaviors on a micro-structured surface using a three dimensional color-gradient lattice Boltzmann model.

Inspired by the experimental work of Raj et al. (high-resolution liquid patterns via three-dimensional droplet shape control), in the present study, a three-dimensional multiphase color-gradient lattice Boltzmann model developed previously by some of the authors is used to simulate droplet dynamic behaviors with different surface micro-pillar arrays. To facilitate the present simulation, wetting boundary conditions are used and the accuracy of color gradient prediction at boundary nodes is enhanced. The experimental findings are confirmed and non-circular contact lines are reproduced numerically for the first time. To justify the existing contact angle formula proposed based on the Wenzel model, a systematic parametric study is conducted, based on which the pillar density is redefined to allow for the influence of pillar height, and then it is used to modify the contact angle. In addition, the evolution of the contact line motion for various droplet shapes is investigated systematically, and both circular and non-circular contact characteristics are well-depicted for different surface micro-pillar arrays.

The increase of O-acetylation and N-deacetylation in cell wall promotes acid resistance and nisin production through improving cell wall integrity in Lactococcus lactis.

Cell wall is closely related to bacterial robustness and adsorption capacity, playing crucial roles in nisin production in Lactococcus lactis. Peptidoglycan (PG), the essential component of cell wall, is usually modified with MurNAc O-acetylation and GlcNAc N-deacetylation, catalyzed by YvhB and XynD, respectively. In this study, increasing the two modifications in L. lactis F44 improved autolysis resistance by decreasing the susceptibility to PG hydrolases. Furthermore, both modifications were positively associated with overall cross-linkage, contributing to cell wall integrity. The robust cell wall rendered the yvhB/xynD-overexpression strains more acid resistant, leading to the increase of nisin production in fed-batch fermentations by 63.7 and 62.9%, respectively. Importantly, the structural alterations also reduced nisin adsorption capacity, resulting in reduction of nisin loss. More strikingly, the co-overexpression strain displayed the highest nisin production (76.3% higher than F44). Our work provides a novel approach for achieving nisin overproduction via extensive cell wall remodeling.

Cascaded photonic crystal fibers for three-stage soliton compression.

Cascaded higher-order soliton compression in photonic crystal fibers (PCFs) is demonstrated, where both the hyperbolic secant and Gaussian input pulses are considered. Detailed fiber designs for three-stage higher-order soliton compression where soliton order is three or non-integer are presented. A highest compression factor of 221.32 has been achieved with only 49.48% pedestal energy.

Applications, prospects and challenges of metal borides in lithium sulfur batteries.

Although the lithium-sulfur (Li-S) battery has a theoretical capacity of up to 1675 mA h g-1, its practical application is limited owing to some problems, such as the shuttle effect of soluble lithium polysulfides (LiPSs) and the growth of Li dendrites. It has been verified that some transition metal compounds exhibit strong polarity, good chemical adsorption and high electrocatalytic activities, which are beneficial for the rapid conversion of intermediate product in order to effectively inhibit the "shuttle effect". Remarkably, being different from other metal compounds, it is a significant characteristic that both metal and boron atoms of transition metal borides (TMBs) can bind to LiPSs, which have shown great potential in recent years. Here, for the first time, almost all existing studies on TMBs employed in Li-S cells are comprehensively summarized. We firstly clarify special structures and electronic features of metal borides to show their great potential, and then existing strategies to improve the electrochemical properties of TMBs are summarized and discussed in the focus sections, such as carbon-matrix construction, morphology control, heteroatomic doping, heterostructure formation, phase engineering, preparation techniques. Finally, the remaining challenges and perspectives are proposed to point out a direction for realizing high-energy and long-life Li-S batteries.

RNA Adduction Resulting from the Metabolic Activation of Myristicin by P450 Enzymes and Sulfotransferases.

Myristicin (MYR) mainly occurs in nutmeg and belongs to alkoxy-substituted allylbenzenes, a class of potentially toxic natural chemicals. RNA interaction with MYR metabolites in vitro and in vivo has been investigated in order to gain a better understanding of MYR toxicities. We detected two guanosine adducts (GA1 and GA2), two adenosine adducts (AA1 and AA2), and two cytosine adducts (CA1 and CA2) by LC-MS/MS analysis of total RNA extracts from cultured primary mouse hepatocytes and liver tissues of mice after exposure to MYR. An order of nucleoside adductions was found to be GAs > AAs > CAs, and the result of density functional theory calculations was in agreement with that detected by the LC-MS/MS-based approach. In vitro and in vivo studies have shown that MYR was oxidized by cytochrome P450 enzymes to 1'-hydroxyl and 3'-hydroxyl metabolites, which were then sulfated by sulfotransferases (SULTs) to form sulfate esters. The resulting sulfates would react with the nucleosides by SN1 and/or SN2 reactions, resulting in RNA adduction. The modification may alter the biochemical properties of RNA and disrupt RNA functions, perhaps partially contributing to the toxicities of MYR.

Mechanism-Based Inactivation of CYP2D6 by Phellopterin and Related Drug-Drug Interaction with Metoprolol.

Phellopterin (PLP) is a linear furanocoumarin widely found in citrus fruits and herbal medicines. The study aims to comprehensively investigate the mechanism of inhibition of CYP2D6 enzyme activity by PLP and its alteration of metoprolol pharmacokinetics. PLP was found to irreversibly inhibit CYP2D6 in time-, concentration-, and nicotinamide adenine dinucleotide phosphate-dependent manners. Coincubation with quinidine, which is a competitive inhibitor of CYP2D6, attenuated this time-dependent inhibition. Glutathione (GSH) and catalase/superoxide dismutase failed to reverse the PLP-induced CYP2D6 inactivation. GSH trapping experiments provided strong evidence that PLP metabolic activation produces epoxide or γ-ketoaldehyde intermediates. In addition, pretreatment with PLP resulted in significant increases in Cmax and area under curve of plasma metoprolol in rats.

Multi-color two-laser super-resolution structured illumination microscopy for the visualization of multi-organelle in living cells.

In this study, we introduced a novel dual-laser multi-color imaging system. Integrated with a multi-channel filter wheel, this system compared three spectral decontamination algorithms (nonnegative matrix factorization [NMF], RCAN, and PICASSO) showcasing its efficacy in achieving four-color imaging with only two laser sources. Combined with a reliable image reconstruction algorithm, the spatial resolution of four channels super-resolution four-color images reached 130, 125, 133, and 132 nm, respectively. Lipid droplets, mitochondria, lysosomes, and nuclei from the mouse hepatocytes (AML12), human neuroblastoma cells (SH-SY5Y), mouse hippocampal neuronal cells (HT-22), and immortalized murine bone marrow-derived macrophages were imaged. At the same time, the chromatin condensation, nuclear contraction, DNA fragmentation, apoptotic body formation, as well as the fusion of Mito and Lyso involved in mitochondrial autophagy were observed in HT-22 and SH-SY5Y cells suffering oxidative stress. Our multi-color SIM imaging system establishes a powerful platform for dynamic organelle studies and other high-resolution investigations in live cells.

Transcranial alternating current stimulation improves quality of life in Parkinson's disease: study protocol for a randomized, double-blind, controlled trial.

BACKGROUND: The neural cells in the brains of patients with Parkinson's disease (PWP) display aberrant synchronized oscillatory activity within the beta frequency range. Additionally, enhanced gamma oscillations may serve as a compensatory mechanism for motor inhibition mediated by beta activity and also reinstate plasticity in the primary motor cortex affected by Parkinson's disease. Transcranial alternating current stimulation (tACS) can synchronize endogenous oscillations with exogenous rhythms, thereby modulating cortical activity. The objective of this study is to investigate whether the addition of tACS to multidisciplinary intensive rehabilitation treatment (MIRT) can improve symptoms of PWP so as to enhance the quality of life in individuals with Parkinson's disease based on the central-peripheral-central theory. METHODS: The present study was a randomized, double-blind trial that enrolled 60 individuals with Parkinson's disease aged between 45 and 70 years, who had Hoehn-Yahr scale scores ranging from 1 to 3. Participants were randomly assigned in a 1:1 ratio to either the tACS + MIRT group or the sham-tACS + MIRT group. The trial consisted of a two-week double-blind treatment period followed by a 24-week follow-up period, resulting in a total duration of twenty-six weeks. The primary outcome measured the change in PDQ-39 scores from baseline (T0) to 4 weeks (T2), 12 weeks (T3), and 24 weeks (T4) after completion of the intervention. The secondary outcome assessed changes in MDS-UPDRS III scores at T0, the end of intervention (T1), T2, T3, and T4. Additional clinical assessments and mechanistic studies were conducted as tertiary outcomes. DISCUSSION: The objective of this study is to demonstrate that tACS can enhance overall functionality and improve quality of life in PWP, based on the framework of MIRT. Additionally, it seeks to establish a potential correlation between these therapeutic effects and neuroplasticity alterations in relevant brain regions. The efficacy of tACS will be assessed during the follow-up period in order to optimize neuroplasticity and enhance its potential impact on rehabilitation efficiency for PWP. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300071969. Registered on 30 May 2023.

SDS-Net: A lightweight 3D convolutional neural network with multi-branch attention for multimodal brain tumor accurate segmentation.

The accurate and fast segmentation method of tumor regions in brain Magnetic Resonance Imaging (MRI) is significant for clinical diagnosis, treatment and monitoring, given the aggressive and high mortality rate of brain tumors. However, due to the limitation of computational complexity, convolutional neural networks (CNNs) face challenges in being efficiently deployed on resource-limited devices, which restricts their popularity in practical medical applications. To address this issue, we propose a lightweight and efficient 3D convolutional neural network SDS-Net for multimodal brain tumor MRI image segmentation. SDS-Net combines depthwise separable convolution and traditional convolution to construct the 3D lightweight backbone blocks, lightweight feature extraction (LFE) and lightweight feature fusion (LFF) modules, which effectively utilizes the rich local features in multimodal images and enhances the segmentation performance of sub-tumor regions. In addition, 3D shuffle attention (SA) and 3D self-ensemble (SE) modules are incorporated into the encoder and decoder of the network. The SA helps to capture high-quality spatial and channel features from the modalities, and the SE acquires more refined edge features by gathering information from each layer. The proposed SDS-Net was validated on the BRATS datasets. The Dice coefficients were achieved 92.7, 80.0 and 88.9% for whole tumor (WT), enhancing tumor (ET) and tumor core (TC), respectively, on the BRTAS 2020 dataset. On the BRTAS 2021 dataset, the Dice coefficients were 91.8, 82.5 and 86.8% for WT, ET and TC, respectively. Compared with other state-of-the-art methods, SDS-Net achieved superior segmentation performance with fewer parameters and less computational cost, under the condition of 2.52 M counts and 68.18 G FLOPs.

Acid-degradable nanocomposite hydrogel and glucose oxidase combination for killing bacterial with photothermal augmented chemodynamic therapy.

Bacterial infection often delays diabetic wound healing, and even causes serious life-threatening complications. Herein, we successfully developed a Cu2O/Pt nanocubes-dopping alginate (ALG)- hyaluronic acid (HA) hydrogel (Cu2O/Pt hydrogel) by simple assembly of the Cu2O/Pt nanocubes and the ALG-HA mixture. The Cu2O/Pt hydrogel combined with the glucose oxidase (GOx) can be used for photothermal- and starving-enhanced chemodynamic therapy (CDT) against Gram-negative and Gram-positive bacteria. The GOx can catalyze the glucose to produce gluconic acid and H2O2 for starvation therapy, following which the released Cu2O/Pt nanocubes react with H2O2 in the acidic microenvironment to generate highly cytotoxic hydroxyl radicals (·OH) for CDT. Additionally, the Cu2O/Pt hydrogel can release copper ions gradually with the decrease of pH induced by gluconic acid, which can increase the protein expression and secretion of vascular endothelial growth factor (VEGF) and promote endothelial cell proliferation, migration and angiogenesis, subsequently promoting diabetic wound healing in rats. Our results suggested that the Cu2O/Pt hydrogel combined with GOx may be a potential therapeutic approach for treating the infected diabetic wound.

Substrate Positioning Dynamics Involves a Non-Electrostatic Component to Mediate Catalysis.

Substrate positioning dynamics (SPD) orients the substrate in the active site, thereby influencing catalytic efficiency. However, it remains unknown whether SPD effects originate primarily from electrostatic perturbation inside the enzyme or can independently mediate catalysis with a significant non-electrostatic component. In this work, we investigated how the non-electrostatic component of SPD affects transition state (TS) stabilization. Using high-throughput enzyme modeling, we selected Kemp eliminase variants with similar electrostatics inside the enzyme but significantly different SPD. The kinetic parameters of these mutants were experimentally characterized. We observed a valley-shaped, two-segment linear correlation between the TS stabilization free energy (converted from kinetic parameters) and substrate positioning index (a metric to quantify SPD). The energy varies by approximately 2 kcal/mol. Favorable SPD was observed for the distal mutant R154W, increasing the proportion of reactive conformations and leading to the lowest activation free energy. These results indicate the substantial contribution of the non-electrostatic component of SPD to enzyme catalytic efficiency.

Improving performances of Lithium-Sulfur cells via regulating of VSe2 functional mediator with Doping-Defect engineering and Electrode-Separator integration strategy.

The sluggish redox kinetics and the severe shuttle effect of soluble lithium polysulfides (LiPSs) are the main key issues which would hinder the development of lithium-sulfur (Li-S) batteries. In this work, a nickel-doped vanadium selenide in-situ grows on reduced graphene oxide(rGO) to form a two-dimensional (2D) composite Ni-VSe2/rGO by a simple solvothermal method. When it is used as a modified separator in Li-S batteries, the Ni-VSe2/rGO material with the doped defect and super-thin layered structure can greatly adsorb LiPSs and catalyze the conversion reaction of LiPSs, resulting in effectively reducing LiPSs diffusion and suppressing the shuttle effect. More importantly, the cathode-separator bonding body is first developed as a new strategy of electrode-separator integration in Li-S batteries, which not only could decrease the LiPSs dissolution and improve the catalysis performance of the functional separator as the upper current-collector, but also is good for the high sulfur loading and the low electrolyte/sulfur (E/S) ratio for high energy density Li-S batteries. When the Ni-VSe2/rGO-PP (polypropylene, Celgard 2400) modified separator is applied, the Li-S cell can retain 510.3 mA h g-1 capacity after 1190 cycles at 0.5C. In the electrode-separator integrated system, the Li-S cell can still maintain 552.9 mA h g-1 for 190 cycles at a sulfur loading 6.4 mg cm-2 and 4.9 mA h cm-2 for 100 cycles at a sulfur loading 7.0 mg cm-2. The experimental results indicate that both the doped defect engineering and the super-thin layered structure design might optimally be chosen to fabricate a new modified separator material, and especially, the electrode-separator integration strategy would open a practical way to promote the electrochemical behavior of Li-S batteries with high sulfur loading and low E/S ratio.

The role of selenium vacancies functionalized mediator of bimetal (Co, Fe) selenide for high-energy-density lithium-sulfur batteries.

Lithium-sulfur (Li-S) batteries are currently only in the basic research stage and have not been commercialized, which is mainly affected by the poor conductivity of sulfur/lithium sulfide (S/Li2S), volume expansion effect of sulfur and the shuttle effect of lithium polysulfides (LiPSs). Herein, a three dimensional (3D) carbon nanotubes (CNTs) decorated cubic Co9Se8-x/FeSe2-y (0 ï¼œ x ï¼œ 8, 0 ï¼œ y ï¼œ 2) composite (Co9Se8-x/FeSe2-y@CNTs) is developed, and used as the functionalized mediator on polypropylene (PP) in Li-S batteries. Benefiting from the good electrical conductivity, large number of Se vacancies and the triple block/adsorption/catalytic effects of Co9Se8-x/FeSe2-y@CNTs, the cell with Co9Se8-x/FeSe2-y@CNTs//PP modified separator delivers a high reversible capacity (1103.5 mA h g-1) at 1C after three cycles activation at 0.5C and remains 446 mA g h-1 after 750 cycles with a 0.08% capacity decay rate each cycle. Moreover, at 0.2C, a high areal capacity of 3.63 mA h cm-2 after 100 cycles with a high sulfur loading of 4.1 mg cm-2 is obtained. The in-situ XRD tests revealing the transition path of α-S8 â†’ Li2S â†’ ß-S8 during the first charge-discharge process, then ß-S8 â†’ Li2S â†’ ß-S8 conversion reaction in the next cycles, and firstly determine the sulfur-selenide active intermediates (Se1.1S6.9) during cycles. The work provides a new insight into the development of bimetallic selenide composites by defect engineering with highly adsorptive and catalytic properties for Li-S batteries.