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High-precision collaborative observation is urgently needed due to the increasing demands of space science missions. Based on a conventional DFP (disturbance-free-payload) configuration, this paper presents a novel DFP that has great potential to deal with collaborative observation missions. The novel DFP system is developed, in which two or more payloads are installed via a non-contact unit and installed parallel configuration. Thus, the novel design is a multibody dynamics system. With the incorporation of the dynamics of the flexible umbilical between the PMs (payload modules) and SM (support module), the six-degrees-of-freedom multibody rigid–flexible dynamics of the whole system are derived. To verify the effectiveness of the novel DFP design in a collaborative observation mission, a multi-loop controller is designed for an inertial Earth collaborative observation mission. Simulation studies are conducted, which indicate that the proposed design can complete collaborative observation and achieve high precision.

Being the S-enantiomer of racemic ketamine, esketamine is found to be effective for sedation, analgesia, and treating depression. However, there is no comprehensive bibliometric analysis about esketamine research. In this study, we aimed to determine the scientific output and emerging topics related to esketamine.Esketamine-related articles and reviews that published between 2000 and 2020 were obtained from the Web of Science Core Collection database, using key word search of "esketamine" "esketamine hydrochloride", "s-ketamine", "S(+)-ketamine", "(S)-ketamine", or "(-)-ketamine". Various bibliographic elements were collected, including the annual number of publications, citation frequency, countries/regions, institutions, authors, journals, and keywords. Two sorts of scientometric software, namely VOS viewer and CiteSpace, were used to conduct bibliometric and knowledge-map analyses.A total of 683 publications were included in the current study. We found the number of publications in esketamine research field had increased annually since 2016. The United States was the leader in this field, with the highest publications number (162, 23.72%), total citations (3504/9713, 36.08%) and H-index (40). The most productive institution was Chiba University in Japan, and esketamine-related papers were mainly published in the journalThe past two decades have shown a marked increase in esketamine research. The United States maintained a top position worldwide, making the most significant contributions in the field of esketamine research. The contributions and collaborations of Asian countries have continuously increased and is a strong area of growth as well as development in recent years. Additionally, the emerging hotspots of esketamine research concentrate on clarifying its depression treatment effect.

A late-stage photoisomerization/cyclization union tactic, in conjunction with Type I Anion Relay Chemistry (ARC), permits enantioselective total syntheses and then biological evaluation of (+)-peniciketals A and B. The photochemical protocol was further showcased by an efficient three-step construction of the architecturally complex polycyclic skeleton found in (-)-diocollettines A. The mechanism and diastereoselectivity of the photochemical protocol have also been explored by both experiment and density functional theory calculations.

Jingyi Du,* Yifan Deng,* Zhuolin Qiu, Guoliang Sun, Yue Guo, Ziqing Hei, Xiang Li Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiang LiDepartment of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Number 600, Tianhe Road, Guangzhou, 510630, People’s Republic of ChinaTel/ Fax +86 20 8525 3132Email lixiang27@mail.sysu.edu.cnPurpose: Cognitive impairment is a complication that most frequently happens in patients with chronic neuropathic pain and has limited effective therapy. The aim of this study was to explore the effects of curcumin on the cognitive deficit in rats with peripheral nerve injury induced-neuropathic pain.Methods: The neuropathic pain rat model was constructed using chronic constriction injury (CCI). The curcumin (60 mg/kg) or vehicle was intraperitoneally administered once a day, beginning at 14th day after surgery and continued for 14 consecutive days. The nociceptive threshold tests were measured by paw mechanical withdraw threshold (PMWT) and paw thermal withdrawal latency (PTWL), while the spatial memory abilities were evaluated by the Morris water maze test. The mean counts of bromodeoxyuridine (Brdu)/neuronal nuclei (NeuN) as well as Brdu/doublecortin (DCX) co-labeled cells were used to evaluate neurogenesis in the dentate gyrus of hippocampus. The ultrastructure of the synapse in hippocampal region was visualized using transmission electron microscopy (TEM).Results: Increased PMWT and PTWL, as well as relieved memory deficits, were found in CCI rats under curcumin administration. Moreover, curcumin treatment increased the number of newly born immature (BrdU/NeuN) and newly generated mature neurons (BrdU/DCX). The TEM examination revealed increased PSD thickness and shorter active zone length as well as narrowed synaptic cleft width in the hippocampal region of CCI rats after curcumin injection.Conclusion: Curcumin can alleviate CCI induced nociceptive behaviors and memory deficit. This effect might be associated with hippocampal neurogenesis and synaptic plasticity improvements, which indicated curcumin as a potential strategy for the cognitive impairment restoration under prolonged neuropathic pain condition.Keywords: curcumin, peripheral nerve injury, cognitive impairment, hippocampus neurogenesis

Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder that affects premenopausal women. The etiology of PCOS is multifaceted, involving various genetic and epigenetic factors, hypothalamic–pituitary–ovarian dysfunction, androgen excess, insulin resistance, and adipose-related mechanisms. High-fat diets (HFDs) has been linked to the development of metabolic disorders and weight gain, exacerbating obesity and impairing the function of the hypothalamic–pituitary–ovarian axis. This results in increased insulin resistance, hyperinsulinemia, and the release of inflammatory adipokines, leading to heightened fat synthesis and reduced fat breakdown, thereby worsening the metabolic and reproductive consequences of PCOS. Effective management of PCOS requires lifestyle interventions such as dietary modifications, weight loss, physical activity, and psychological well-being, as well as medical or surgical interventions in some cases. This article systematically examines the pathological basis of PCOS and the influence of HFDs on its development, with the aim of raising awareness of the connection between diet and reproductive health, providing a robust approach to lifestyle interventions, and serving as a reference for the development of targeted drug treatments.

The enantioselective total syntheses of (+)-peniciketals A and B, two members of a family of architecturally complex spiroketals, have been achieved. Key synthetic transformations comprise Type I Anion Relay Chemistry (ARC) to construct the benzannulated [6,6]-spiroketal skeleton, a Negishi cross-coupling/olefin cross-metathesis reaction sequence to generate the trans-enone structure, and a late-stage large fragment union exploiting our recently developed photoisomerization/cyclization tactic.

The identification of active binding drugs for target proteins (referred to as drug–target interaction prediction) is the key challenge in virtual screening, which plays an essential role in drug discovery. Although recent deep learning-based approaches achieve better performance than molecular docking, existing models often neglect topological or spatial of intermolecular information, hindering prediction performance. We recognize this problem and propose a novel approach called the Intermolecular Graph Transformer (IGT) that employs a dedicated attention mechanism to model intermolecular information with a three-way Transformer-based architecture. IGT outperforms state-of-the-art (SoTA) approaches by 9.1% and 20.5% over the second best option for binding activity and binding pose prediction, respectively, and exhibits superior generalization ability to unseen receptor proteins than SoTA approaches. Furthermore, IGT exhibits promising drug screening ability against severe acute respiratory syndrome coronavirus 2 by identifying 83.1% active drugs that have been validated by wet-lab experiments with near-native predicted binding poses. Source code and datasets are available at https://github.com/microsoft/IGT-Intermolecular-Graph-Transformer.

Purpose: This study aimed to investigate the effect of transforming growth factor-β1 (TGF-β1) on the migration capacity of rat vascular smooth muscle cells (VSMCs) and its potential mechanism.Methods: Different concentrations of TGF-β1 were used to treat rat VSMCs. The migration capacity of cells was observed by wound healing assay and Transwell assay. Western Blotting and Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) were performed to examine the expression of EMT related gene.Results: In a certain concentration range, the migration ability of rat VSMCs was enhanced with the increase of TGF-β1 concentration. Meanwhile, TGF-β1 increased the expression of N-cadherin and Vimentin (mesenchymal markers), and decreased the expression of E-cadherin and β-catenin (epithelial markers) at both protein and mRNA levels. Conclusion: TGF-β1 promoted abnormal migration of rat VSMCs by regulating the expression of EMT related genes. This may be one of the mechanisms of in-stent restenosis (ISR) in coronary arteries.

Cells exposed with irradiation can induce different biological effects in non-irradiated cells due to the cell-cell interactions. Herein, we investigated the bystander effect of different types of irradiation including gamma irradiation (GR) and lithium heavy ion irradiation (LR) on the model human neuroblastoma cell line (SH-SY5Y). The gamma and lithium ion irradiation induced different bystander effects on the SH-SY5Y cell line. The bystander effect induced by gamma irradiation promoted the cell proliferation through activating the ERK and AKT signaling pathways, but it could slightly influence the cell cycle of non-irradiated SH-SY5Y cells. Whereas, the bystander effect induced by lithium heavy ion irradiation inhibited the cell proliferation, arrested the cell cycle and activated the process of pro-apoptosis. The findings of this study confirm the diversified bystander effects of various irradiation on the non-irradiated cells, therefore it highlights the importance of revised strategy for clinical radiotherapy and radioprotection to reduce the damages caused by bystander effects. Further, the in-depth mechanism research on the cell proliferation influenced by the bystander effect of radiation will also be useful to understand the biological effects of radiation.

The progress of space science and technology has ushered in a new era for humanity’s exploration of outer space. Recent studies have indicated that the aerospace special environment including microgravity and space radiation poses a significant risk to the health of astronauts, which involves multiple pathophysiological effects on the human body as well on tissues and organs. It has been an important research topic to study the molecular mechanism of body damage and further explore countermeasures against the physiological and pathological changes caused by the space environment. In this study, we used the rat model to study the biological effects of the tissue damage and related molecular pathway under either simulated microgravity or heavy ion radiation or combined stimulation. Our study disclosed that ureaplasma-sensitive amino oxidase (SSAO) upregulation is closely related to the systematic inflammatory response (IL-6, TNF-α) in rats under a simulated aerospace environment. In particular, the space environment leads to significant changes in the level of inflammatory genes in heart tissues, thus altering the expression and activity of SSAO and causing inflammatory responses. The detailed molecular mechanisms have been further validated in the genetic engineering cell line model. Overall, this work clearly shows the biological implication of SSAO upregulation in microgravity and radiation-mediated inflammatory response, providing a scientific basis or potential target for further in-depth investigation of the pathological damage and protection strategy under a space environment.

A hybrid energy storage system (HESS) consists of two or more types of energy storage components and the power electronics circuit to connect them. Therefore, the real-time capacity of this system highly depends on the state of the system and cannot be simply evaluated with traditional battery models. To tackle this challenge, an equivalent state of charge (ESOC) which reflects the remaining capacity of a HESS unit in a specific operation mode, is proposed in this paper. Furthermore, the proposed ESOC is applied to the control of the distributed HESS which contains several units with their own local targets. To optimally distribute the overall power target among these units, a sparse communication network-based hierarchical control framework is proposed. This framework considers the distributed control and optimal power distribution in the HESS from two aspects - the power output capability and the ESOC balance. Based on the primary droop control, the total power is allocated according to the maximum output capacity of each unit, and the secondary control is used to adjust the power from the perspective of ESOC balance. Therefore, each energy storage unit can be controlled to meet the local power demand of the microgrid. Simulation results based on MATLAB/Simulink verify the effectiveness of the application of the proposed equivalent SOC. National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [51877041] Published version This work was supported by the National Natural Science Foundation of China under Grant 51877041.

Drug–drug interactions (DDIs) are one of the major concerns in pharmaceutical research, and a number of computational methods have been developed to predict whether two drugs interact or not. Recently, more attention has been paid to events caused by the DDIs, which is more useful for investigating the mechanism hidden behind the combined drug usage or adverse reactions. However, some rare events may only have few examples, hindering them from being precisely predicted. To address the above issues, we present a few-shot computational method named META-DDIE, which consists of a representation module and a comparing module, to predict DDI events. We collect drug chemical structures and DDIs from DrugBank, and categorize DDI events into hundreds of types using a standard pipeline. META-DDIE uses the structures of drugs as input and learns the interpretable representations of DDIs through the representation module. Then, the model uses the comparing module to predict whether two representations are similar, and finally predicts DDI events with few labeled examples. In the computational experiments, META-DDIE outperforms several baseline methods and especially enhances the predictive capability for rare events. Moreover, META-DDIE helps to identify the key factors that may cause DDI events and reveal the relationship among different events.

A novel non-contact satellite for drag-free and attitude control is proposed in this paper. The non-contact satellite is separated into a payload module and a service module by non-contact Lorentz actuators. Instead of thrusters, the non-contact Lorentz actuators are used to exerted precise forces and torques, enabling drag-free and attitude control of the payload module, while the service module is designed to track the payload module to avoid collision. On the basis of this new design, the dynamics of drag-free and attitude control can be precisely modeled. Accordingly, a hierarchical control algorithm, consisting of an EKF-based estimation and rejection of environmental acceleration of payload module, attitude control of payload module, minimum norm allocation of non-contact Lorentz actuators, as well as collaborative control of service module, is systematically designed. A numerical simulation is then conducted to demonstrate the validity and effectiveness of the proposed design.

Disturbance-Free-Payload is a novel spacecraft architecture proposed to achieve perfect vibration isolation performance of space applications. In this paper, the object under study is a DFP system in which a flexible umbilical connection between the support module (SM) and the payload module (PM) is introduced for data, power and fluid transfer. Bead model accounting for properties of mass and flexibility, is utilized to model the flexible umbilical. With incorporation of bead model, six degree-of-freedom multibody rigid-flexible dynamics for the DFP system is established via Newtonian mechanics. Along with rotational coupling between solar panels and SM, translational coupling, in particular, is taken into consideration since there is a stringent requirement on relative position between PM and SM. Based on the accurate motion equations of the DFP system, simulation studies are conducted to gain insight of the impact of umbilical connection and translational coupling on pointing performance of the DFP system. Simulation results validate effectiveness of DFP configuration in isolating vibrations transmitted from SM to PM. Besides, umbilical connection plays an important part in degrading pointing performance of PM whereas it exerts little impact on SM. Moreover, translational coupling leads to significant pointing performance degradation for both PM and SM.

In this paper, a three-dimensional (3D) impact-angle-control guidance law is proposed based on the approaches of nonsingular terminal sliding mode control and fixed-time convergence theory to intercept a maneuvering target. The guidance law is derived based on the coupled 3D engagement dynamics. To intercept the target with an expected impact angle, the nonsingular terminal sliding mode control is designed to ensure that the line-of-sight (LOS) angles and rates rapidly reach the desired values. Furthermore, the fixed-time convergence algorithm is proposed to guarantee that the LOS angles and rates are convergent in fixed time. The upper bound of the settling time can be obtained by presetting the parameters of the proposed guidance law, and it is independent of the initial conditions. The stability of the guidance system is proven via Lyapunov stability theory. The simulation results are presented to validate the efficiency and superiority of the proposed guidance law.

Diabetic neuropathic pain (DNP) is a highly prevalent complication of diabetes mellitus (DM) without effective treatments. The present study aimed to explore the effects of ferrostatin-1 (Fer-1) on mechanical hypersensitivity and spinal ferroptosis in rats with DM induced with streptozotocin (STZ). One week after STZ injection, the DM rats intraperitoneally received Fer-1 (2 μmol/kg) or a vehicle (1% DMSO) once daily for consecutive two weeks. The paw mechanical withdrawal thresholds (PMWT) were assessed weekly to investigate the nociceptive threshold. Biochemical and morphological alterations associated with spinal ferroptosis, including iron content, lipid peroxidation assays, the activities of anti-acyl-CoA synthetase long-chain family member 4 (ACSL4) and glutathione peroxidase 4 (GPX4), and mitochondrial morphology, were also evaluated. Decreased PMWT and significant changes in ferroptosis-associated markers, such as iron overload, lipid peroxidation, increased expression levels of ACSL4 and decreased expression levels of GPX4, and disrupted morphological features in mitochondria were found in rats with STZ-induced DM. These effects were significantly attenuated via intraperitoneal administration of the ferroptosis inhibitor Fer-1. Our findings indicated the involvement of iron-dependent ferroptosis in the spinal cords of rats with STZ-induced DM, and highlighted the effect of continuous administration of ferroptosis inhibitors such as Fer-1 on hypersensitivity in DM rats. These results suggest that inhibition of ferroptosis might be a potential therapeutic strategy in DNP treatment.

Multi-component union tactics in which three or more fragments are rapidly assembled are highly prized in the construction of architecturally complex natural products. Anion Relay Chemistry (ARC), a multi-component union tactic, has just such potential to elaborate structurally diverse scaffolds in a single operation with excellent stereochemical control. Conceptually, the ARC tactic can be divided into two main classes: “Through-Bond”, by the relay of negative charge through the bonding system of a molecule; and “Through-Space”, by the migration of negative charge across space by a transfer agent. “Through-Space” Anion Relay Chemistry, the focus of this Account, can be further subdivided into two types: Type I ARC, originated from Tietze-Schaumann-Smith coupling reaction, which for the first time permits controllable Brook rearrangements to construct unsymmetrical adducts, and as such has been successfully employed in the total syntheses of diverse natural products, including the mycoticins, bryostatin 1, spongistatins, rimocidin, indolizidine alkaloids, and enigmazole A; and Type II ARC, central to which is the design of novel bifunctional linchpins that enable rapid assembly of linear and cyclic fragments with diverse architectural features, ranging from polyols, spiroketals and polyenes to polypropionate scaffolds. Recently, the Type II ARC tactic has been exploited as the key construction tactic in the total syntheses of the spirastrellolides, the cryptocarya acetates, secu’amamine A, mandelalide A and nahuoic acid C(i) (B(ii)). This Account will present the evolution of both the Type I and Type II Anion Relay tactics, in conjunction with some prominent applications. [Image: see text]

Motivation Drug–drug interactions (DDIs) are one of the major concerns in pharmaceutical research. Many machine learning based methods have been proposed for the DDI prediction, but most of them predict whether two drugs interact or not. The studies revealed that DDIs could cause different subsequent events, and predicting DDI-associated events is more useful for investigating the mechanism hidden behind the combined drug usage or adverse reactions. Results In this article, we collect DDIs from DrugBank database, and extract 65 categories of DDI events by dependency analysis and events trimming. We propose a multimodal deep learning framework named DDIMDL that combines diverse drug features with deep learning to build a model for predicting DDI-associated events. DDIMDL first constructs deep neural network (DNN)-based sub-models, respectively, using four types of drug features: chemical substructures, targets, enzymes and pathways, and then adopts a joint DNN framework to combine the sub-models to learn cross-modality representations of drug–drug pairs and predict DDI events. In computational experiments, DDIMDL produces high-accuracy performances and has high efficiency. Moreover, DDIMDL outperforms state-of-the-art DDI event prediction methods and baseline methods. Among all the features of drugs, the chemical substructures seem to be the most informative. With the combination of substructures, targets and enzymes, DDIMDL achieves an accuracy of 0.8852 and an area under the precision–recall curve of 0.9208. Availability and implementation The source code and data are available at https://github.com/YifanDengWHU/DDIMDL. Supplementary information Supplementary data are available at Bioinformatics online.

A synchronous control of relative attitude and position is required in separated ultra-quiet spacecraft, such as drag-free, disturbance-free, and distributed spacecraft. Thus, a twistor-based synchronous sliding mode control is investigated in this paper to solve the control problem of relative attitude and position among separated spacecraft modules. The twistor-based control design and the stability proof are implemented using the Modified Rodrigues Parameter (MRP). To evaluate the effectiveness of the proposed control method, this paper presents a case study of separated spacecraft flying control considering the mass uncertainty and external disturbances. In addition, a simulation study of the Proportional-Derivative (PD) control is also presented for comparison. The results indicate that the twistor-based sliding mode controller can ensure global asymptotic stability. The states converge fast with ultra-precision and ultra-stability in both the attitude and position. Moreover, the proposed twistor-based sliding mode control system is robust to the mass uncertainty and external disturbances. Keywords: Distributed spacecraft, Gravitational wave detection, Synchronous control, Ultra-precision, Ultra-stability

Microwave-assisted catalysis offers great promise as an “intensified” technology for chemical processing. The present study investigates microwave-assisted direct conversion of methane with focus on the design and evaluation of microwave-sensitive H-(Fe)ZSM-5 catalysts for the existence of hotspot formation. Isomorphous substituted H-(Fe)ZSM-5 catalysts are tuned to identify key design parameters that control their microwave sensitivity. Increasing the amount of Al and Fe substitution in the zeolite lattice is found to result in higher microwave sensitivity due to improved dielectric properties and hence facilitated microwave heating of the catalyst bed. Comparison between the performance of these catalysts in a conventional thermally-heated (CH) fixed-bed and a microwave (MW) reactor allows identification of the effect of microwave irradiation on the catalyst activity. Methane conversion is drastically enhanced at MW conditions (from 3% at CH conditions to 40% at MW conditions), indicating accelerated methane activation over the metal site and hence suggesting a hot metal site despite much lower catalyst bulk temperature measured in the microwave reactor. The existence of metal hotspot formation is further supported by the reaction product distribution and spent catalyst analysis. At MW conditions, C2 (ethane and ethylene) and coke (mainly carbon nanotubes and nanofibers) selectivity are much higher at the cost of aromatics make compared to CH conditions. This can be explained by reduced aromatization activity at the Bronsted acid sites of the zeolite due to its lower relative temperature of the zeolite. The much-enhanced metal aggregation observed in the spent catalyst from the MW reactor along with the distribution of coke species further confirms the existence of selective heating (i.e. hotspot formation) occurring at the active metal site in the catalyst at MW conditions.

A convergent total synthesis of (−)-nahuoic acid Ci(Bii) (3), a novel cis-decalin polyketide, has been achieved. Key synthetic transformations include Type II Anion Relay Chemistry (ARC) to construct the polyol chain, a Ti-catalyzed asymmetric Diels–Alder reaction to generate the cis-decalin skeleton, and a late-stage large fragment union exploiting a Micalizio alkoxide-directed alkyne–alkene coupling tactic.

In this review article, the latest developments of the four most common additive manufacturing methods for metallic materials are reviewed, including powder bed fusion, direct energy deposition, binder jetting, and sheet lamination. In addition to the process principles, the microstructures and mechanical properties of AM-fabricated parts are comprehensively compared and evaluated. Finally, several future research directions are suggested.

Three catalyst-dependent divergent reaction pathways for reactions of propargyl aryldiazoacetates are disclosed. Transition metal catalysts including those of rhodium(II), palladium(0 and II), silver(I), mercury(II), copper(I and II), platinum(II), and cationic gold(I) are effective for reactions that proceed through dinitrogen extrusion, carbene/alkyne metathesis, and aromatic substitution to form fused indeno-furanones, and use of tetrakis(acetonitrile)copper(I) provides indeno-furanones in the highest product yields. A Lewis acid catalyzed pathway that forms furan-2-ones is uncovered with FeCl3, ZnBr2, and BF3·Et2O as catalysts that proceed through activation of the aryldiazoacetate ester for arylpropargyl cation dissociation followed by recombination through cation addition to the diazo carbon. Neutral gold catalysts selectively activate the triple bond of propargyl aryldiazoacetates, resulting in the formation of allenic aryldiazoesters that further undergo uncatalyzed rearrangement.

DFT exploration of 1,5- and 1,6-hydrogen atom transfers (HAT), radical addition, and relay to alkene is reported. The reactivity of 1,5- and 1,6-HAT are similar. We also explored reactions involving a multiple radical transferring process. Initially generated radicals undergo a multiple HAT process to form multiple bonds in a “relay” fashion, provided by exquisitely balanced rates.

Visible-light-induced generation of dithianyl and dioxolanyl radicals via selective hydrogen atom transfer (HAT) has been achieved. This radical relay tactic enables remote C(sp(3))—H functionalization to permit rapid access to polyol and spiroketal segments, and in turn has been exploited as a key synthetic construct in the total synthesis of the danshenspiroketallactones. The conformational stability of the danshenspiroketallactones has also been defined via experiments and DFT calculations.