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Ethers are among the most important chemicals in organic synthesis, the pharmaceutical industry, agrochemical production, and material science. C–O bond formation via substitution is one of the most widely used strategies for ether formation. However, known methods usually employ transition-metal and bases to facilitate the process. In this work, we describe the base- and transition-metal-free ether formation via alcohol and phenol-participated substitution. The protocol allows access to a large number of ethers with enyne functional moieties, and features mild reaction conditions, high efficiency, and good regio- and stereoselectivities. The reaction could be readily scaled up, and the products could be used in a range of further transformations.

Flexible electronic skin (e-skin) can enable robots to have sensory forms similar to human skin, enhancing their ability to obtain more information from touch. The non-invasive nature of electrical impedance tomography (EIT) technology allows electrodes to be arranged only at the edges of the skin, ensuring the stretchability and elasticity of the skin’s interior. However, the image quality reconstructed by EIT technology has deteriorated in multi-touch identification, where it is challenging to clearly reflect the number of touchpoints and accurately size the touch areas. This paper proposed an EIT-based flexible tactile sensor that employs self-made hydrogel material as the primary sensing medium. The sensor’s structure, fabrication process, and tactile imaging principle were elaborated. To improve the quality of image reconstruction, the fast iterative shrinkage-thresholding algorithm (FISTA) was embedded into the EIDORS toolkit. The performances of the e-skin in aspects of assessing the touching area, quantitative force sensing and multi-touch identification were examined. Results showed that the mean intersection over union (MIoU) of the reconstructed images was improved up to 0.84, and the tactile position can be accurately imaged in the case of the number of the touchpoints up to seven (larger than two to four touchpoints in existing studies), proving that the combination of the proposed sensor and imaging algorithm has high sensitivity and accuracy in multi-touch tactile sensing. The presented e-skin shows potential promise for the application in complex human–robot interaction (HRI) environments, such as prosthetics and wearable devices.

The use of single-molecule optical tweezers shows that complexin-1 shapes the assembly of the Synaptic-soluble N-ethylmaleimide-sensitive factor Attachment Receptor by multiple domains’ coordination.

Abstract During the Earth's magnetic reversal, the dipole component of the magnetic field weakens, and the non‐dipole component becomes dominant, resulting in a far more complex magnetospheric topology than that of a dipole. In this study, we used a particle tracing technique to investigate the motion of ions within an irregular magnetosphere during the Matuyama‐Brunhes magnetic polarity reversal. Compared to the scenario in which the geomagnetic field is dominated by a dipole component, earthward‐moving particles can be hardly “trapped” in the inner magnetosphere when the geomagnetic field experiences the polarity reversal, and particles can directly precipitate into the Earth's atmosphere on a global scale. It suggests that under an irregular magnetospheric configuration, the traditional trapped region of particles (e.g., radiation belt or ring current) no longer exists.

Magnetopause reconnection is a fundamental mechanism for mass and energy transfer in terrestrial planetary systems. Unlike Earth, Mars lacks a global magnetic field and instead has localized crustal magnetic fields, which can create structures morphologically similar to a scaled-down intrinsic magnetosphere, potentially forming mini-magnetospheres. In this study, we investigate reconnection in Martian mini-magnetospheres on the dayside, analyzing key characteristics of the reconnecting current sheet, and the associated ion escape rate, and comparing these features to reconnection events at the induced magnetopause documented in previous studies. Our observations reveal that, in the subsolar region, the thickness of the Martian mini-magnetopause is comparable to the upstream proton inertial length and the convective gyroradius of the magnetosheath solar wind. However, at higher solar zenith angles, this thickness increases to several times these characteristic lengths. Reconnection-driven ion escape rates at the induced magnetopause are at least 1 order of magnitude greater than those associated with mini-magnetopause reconnection. These findings provide new insights into reconnection processes at Martian boundary layers.

We investigate the seasonal variations of ion precipitation, utilizing observations from the Mars Atmosphere and Volatile Evolution mission spanning from 2014 January 4 to 2023 February 14. Our analysis reveals that a diminishing pattern characterizes the transition from Mars season L _s 0°–180° to Mars season L _s 180°–360°, manifesting as a reduction in precipitating ion fluxes. Additionally, we discern a significant influence of the crustal magnetic field on the seasonal variations in precipitating ion fluxes. Intriguingly, within regions where the crustal magnetic field exhibits a strong quasi-horizontal orientation, opposite seasonal trends become evident. The underlying physical mechanism driving these seasonal variations in ion precipitation is probably attributed to the mass loading effect that may decelerate the solar wind and influence the magnetic pileup. A detailed investigation is further demanded in the future.

Ethnopharmacological relevance: Guipi Tang (GPT) is a widely used traditional Chinese medicine that is used to treat major depressive disorder. However, the molecular mechanisms of its effects remain unclear. Aim of the study: This study aimed to investigate the antidepressant-like effects of GPT and explore its underlying molecular mechanisms. Materials and methods: Male Sprague–Dawley rats were subjected to a chronic unpredictable mild stress (CUMS) procedure and treated with various doses of GPT, with fluoxetine treatment as a positive control. Behavioural tests (including sucrose preference test, novelty-suppressed feeding test, open-field test and forced swim test), terminal deoxynucleotidyl transferase dUTP nick end labeling and enzyme-linked immunosorbent assay were conducted. The levels of Bax, Bcl-2, cleaved caspase-3, PI3K, p-PI3K, AKT, p-AKT, BDNF, TrkB and CREB or p-CREB were assessed at the protein level using western blotting or immunofluorescence. Results: GPT consists of mainly known drugs, such as liquiritin and ginsenosides. It reversed depressive behaviours and decreased cell apoptosis in the hippocampi of CUMS rats. It significantly upregulated the protein level of Bax, p-Akt, p-PI3K, BDNF, TrkB and p-CREB and downregulated the level of cleaved caspase-3 and Bcl-2. Conclusions: GPT had anti-depressive activity as indicated by the amelioration of depression-like behaviour and the inhibition of hippocampal neuronal apoptosis in CUMS rats. This inhibition was mediated partly by modulating the PI3K/Akt and/or BDNF/TrkB/CREB pathway, in which, glycosides, the main components of GPT, might be involved.

Abstract Background Genetic diversity of the human LPA gene locus is associated with high plasma concentrations of lipoprotein(a) [Lp(a)]. High Lp(a) concentrations are strongly associated with a high incidence rate of ischaemic stroke. Case presentation A 46-year-old female Chinese patient suffered from ischaemic stroke. Upon admission to the hospital, the patient was diagnosed with an elevated level of plasma Lp(a). The patient’s clinical symptoms were alleviated by administration of basilar artery stent thrombectomy, mannitol, and aspirin. A novel compound heterozygous deletion of the region containing exons 3–16 covering kringle IV copy number variation (KIV CNV) domains in the LPA gene was observed in genetic analysis by next-generation sequencing and confirmed by qPCR. Conclusions In the current study, we reported a case of a 46-year-old female patient diagnosed with ischaemic stroke. This novel heterozygous deletion mutation in the LPA gene expands the spectrum of LPA mutations. Further study is required to understand the mechanism of LPA mutations in ischaemic stroke.

The interplanetary magnetic field (IMF) By component can cause asymmetric features in the magnetosphere-ionosphere system and influence the electromagnetic energy input. In this study, we use the Space Weather Modeling Framework (SWMF) to study the transient dynamics after a sudden change in the IMF By component exerts on the magnetosphere system. Simulation results reveal that under northward IMF conditions, an abrupt change of the IMF By from duskward to dawnward induces a dawnward geomagnetic field firstly in the cusp region and then in both the near-Earth and magnetotail regions. The signal of the new y-component of the geomagnetic field in the near-Earth region extends tailward while that in the magnetotail moves Earthward, leading the middle-tail region to react last. We investigate in detail the transitional change of the y-component of the geomagnetic field and compare it to the scenario under southward IMF conditions, and find that the latter case reacts in a much simpler manner and the responses are faster globally.

Abstract Background The poor prognosis of patients with ovarian cancer is mainly due to cancer progression. γ-Synuclein (SNCG) has reported as a critical player in cancer metastasis. However, its biological roles and mechanism are yet incompletely understood in ovarian cancer, especially in high-grade serous ovarian cancer (HGSOC). Methods This is a retrospective study of 312 patients with ovarian cancer at a single center between 2006 and 2016. Ovarian cancer tissues were stained by immunohistochemistry to analyze the relationship between SNCG expression and clinicopathologic factors. The clinical outcomes versus SNCG expression level were evaluated by Kaplan–Meier method and multiple Cox regression analysis. Next, systematical functional experiments were given to examine the proliferation and metastatic abilities of SNCG both in vitro and in vivo using loss- and gain- of function approaches. Furthermore, the mechanisms of SNCG overexpression were examined by human phospho-kinase array kit and western blot analysis. Results Clinically, the expression of SNCG was significantly upregulated in ovarian cancer compared with the borderline and benign tumor, normal ovary, and fallopian tube. Notably, the high level of SNCG correlated with high-risk clinicopathologic features and showed poor survival for patients with HGSOC, indicating an independent prognostic factor for these patients. Functionally, we observed that overexpression of SNCG promoted cell proliferation, tumor formation, migration, and invasion both in vitro and in vivo. Mechanistically, we identified that SNCG promoted cancer cell metastasis through activating the PI3K/AKT signaling pathway. Conclusions Our results reveal SNCG up-regulation contributes to the poor clinical outcome of patients with HGSOC and highlight the metastasis-promoting function of SNCG via activating the PI3K/Akt signaling pathway in HGSOC.

ObjectiveTo study the mechanism of the effect of Wen-Shen-Jian-Pi (WSJP) prescription on an ALS model comprising mice knocked out for an encoding RNA editing, mice (AR2).MethodsTwenty-four transgenic AR2 mice were randomly divided into a vehicle group, a low dose WSJP group (15 mg), a medium-dose WSJP group (30 mg), and a high-dose WSJP group (45 mg) (all n = 6 per group). In the treatment groups, the WSJP prescription was given once a day while the vehicle group was fed the same volume of water. The weekly changes in body weight, rotarod test, and grip strength were used to detect the changes in the AR2 and changes of the number of normal mitochondria, abnormal mitochondria, and autophagosomes in injured spinal cord cells were used to evaluate the pathogenetic effects of WSJP treatment.ResultsThe WSJP-treated AR2 mice gained weight more quickly from 8 weeks, and showed active behavior and displayed significantly better constant rotarod scores and grip strengths during the experiment compared with those of the vehicle AR2 mice. The number of normal mitochondria in the WSJP-treated AR2 mice had significantly more normal mitochondria than the vehicle group, while the numbers of abnormal mitochondria and autophagosomes were greatly decreased compared with those in the vehicle group.ConclusionThe WSJP prescription could delay the decline in motor function of ALS model mice by reducing the degeneration of neurons. The potential of WSJP to treat ALS should be assessed in a clinical trial.

Background and PurposeMalnutrition is highly prevalent in ischemic stroke patients. We aimed to investigate whether malnutrition indexes may be useful in predicting mortality at 90 days in ischemic stroke patients treated with intravenous thrombolysis.MethodsWe retrospectively analyzed consecutive patients who underwent thrombolytic therapy at three comprehensive stroke centers. Malnutrition was assessed using the controlling nutritional status (CONUT) score, geriatric nutritional risk index (GNRI), and prognostic nutritional index (PNI).ResultsOf 979 patients (mean age, 66.8 years; males, 63.6%) included in this study, 91 (9.3%; 95% confidence interval [CI]: 8.4–10.2%) died at 3-month follow up. According to the CONUT, GNRI, and PNI scores, 9.9, 33.7, and 7.0% of patients were moderately or severely malnourished, respectively; 64.0% were at least mildly malnourished by at least 1 malnutrition index. In the multivariate regression model after adjusting for potential confounders, malnutrition (severe risk versus normal nutritional status) was significantly associated with an increased risk of mortality for CONUT scores (adjusted odds ratio [OR] 16.16, 95%CI, 7.86-67.11; P < 0.001), GNRI scores (adjusted OR 9.82, 4.10-23.51; P < 0.001) and PNI scores (adjusted OR 12.74, 5.56-29.19; P < 0.001). Similar results were found when the malnutrition scores were analyzed as continuous variables. Adding the three malnutrition indexes to models containing conventional risk factors significantly improved risk reclassification for 3-month mortality.ConclusionOur study showed that malnutrition may be associated with a higher risk of mortality at 3 months in ischemic stroke after intravenous thrombolysis.

BackgroundBreast cancer (BRCA) is the most common cancer in women, while the bones are one of the most common sites of metastasis. Although new diagnostic methods or radiation or chemotherapies and targeted therapies have made huge advances, the occurrence of bone metastasis is also linked with poorer survival. Enhancer RNAs (eRNAs) have been demonstrated to participate in the progression of tumorigenesis and metastasis. However, the role of eRNAs in BRCA bone metastasis remains largely unclear.MethodGene expression profiling of 1,211 primary BRCA and 17 bone metastases samples were retrieved from The Cancer Genome Atlas (TCGA) database, and the significant prognostic eRNAs were identified by Cox regression and least absolute shrinkage and selection operator (LASSO) regression. The acceptable accuracy and discrimination of the nomogram were indicated by the receiver operating characteristic (ROC) and the calibration curves. Then target genes of eRNA, immune cell percentage by CIBERSORT analysis, immune genes by single-sample gene set enrichment analysis (ssGSEA), hallmark of cancer signaling pathway by gene set variation analysis (GSVA), and reverse phase protein array (RPPA) protein chip were used to build a co-expression regulation network and identified the key eRNAs in bone metastasis of BRCA. Finally, Cell Counting Kit-8 (CCK8) assay, cell cycle assay, and transwell assay were used to study changes in cell proliferation, migration, and invasiveness. Immunoprecipitation assay and Western blotting were used to test the interaction and the regulation signaling pathways.ResultsThe 27 hub eRNAs were selected, and a survival-related linear risk assessment model with a relatively high accuracy (area under curve (AUC): 0.726) was constructed. In addition, seven immune-related eRNAs (SLIT2, CLEC3B, LBPL1, FRY, RASGEF1B, DST, and ITIH5) as prognostic signatures for bone metastasis of BRCA were further confirmed by LASSO and multivariate Cox regression and CIBERSORT analysis. Finally, in vitro assay demonstrated that overexpression of SLIT2 reduced proliferation and metastasis in BRCA cells. Using high-throughput co-expression regulation network, we identified that SLIT2 may regulating P38 MAPK/c-Fos signaling pathway to promote the effects of metastasis.ConclusionBased on the co-expression network for bone metastasis of BRCA, we screened key eRNAs to explore a prognostic model in predicting the bone metastasis by bioinformatics analysis. Besides, we identified the potential regulatory signaling pathway of SLIT2 in BRCA bone metastasis, which provides a promising therapeutic strategy for metastasis of BRCA.

An amendment to this paper has been published and can be accessed via the original article.

Abstract Introduction Osteoarthritis (OA) is an inflammatory disease of the joints that causes progressive disability in the elderly. Reactive oxygen species (ROS) play an important role in OA development; they may activate the NLRP3 inflammasome, thereby inducing the secretion of proinflammatory IL-1β and IL-18, leading to the aggravation of the downstream inflammatory response. Nrf2 is a key transcription factor that regulates the expression of antioxidant enzymes that protect against oxidative stress and tissue damage. We aimed to explore the underlying mechanism of OA development by investigating NLRP3, ASC, Nrf2, and HO-1 expression in synovia and their regulatory networks in OA. Methods Human total knee replacement samples were subjected to histology and micro-CT analysis to determine the pathological changes in the cartilage and subchondral bone and to assess the expression of inflammation-related markers in the synovial tissue by immunohistochemistry (IHC), qRT-PCR, and Western blot. To investigate these pathological changes in an OA animal model, adult Sprague-Dawley rats were subjected to anterior cruciate ligament transection and medial meniscectomy. Articular cartilage and subchondral bone changes and synovial tissue were also determined by the same methods used for the human samples. Finally, SW982 cells were stimulated with lipopolysaccharide (LPS) as an in vitro inflammatory cell model. The correlation between NLRP3 and Nrf2 expression was confirmed by knocking down NLRP3 or Nrf2. Results Cartilage destruction and subchondral bone sclerosis were found in the OA patients and OA model rats. Significantly increased expression levels of NLRP3, ASC, Nrf2, and HO-1 were found in the synovial tissue from OA patients. NLRP3, ASC, Nrf2, and HO-1 expression in the synovium was also upregulated in the OA group compared with the sham group. Furthermore, the NLRP3, Nrf2, HO-1, IL-1β, and IL-18 expression in LPS-treated SW982 cells was increased in a dose-dependent manner. As expected, the expression of NLRP3 was upregulated, and the expression of IL-1β and IL-18 was downregulated after Nrf2 silencing. However, knocking down NLRP3 did not affect the expression of Nrf2. Conclusions ROS-induced oxidative stress may be the main cause of NLRP3 inflammasome activation and subsequent release of downstream factors during OA development. Nrf2/HO-1 signaling could be a key pathway for the activation of the NLRP3 inflammasome, which may contribute to the progression of OA. Herein, we discovered a novel role of Nrf2/HO-1 signaling in the production of NLRP3, which may facilitate the prevention and treatment of OA.

Abstract Background Diabetes has become one of the hot topics in life science researches. To support the analytical procedures, researchers and analysts expend a mass of labor cost to collect experimental data, which is also error-prone. To reduce the cost and to ensure the data quality, there is a growing trend of extracting clinical events in form of knowledge from electronic medical records (EMRs). To do so, we first need a high-coverage knowledge base (KB) of a specific disease to support the above extraction tasks called KB-based Extraction. Methods We propose an approach to build a diabetes-centric knowledge base (a.k.a. DKB) via mining the Web. In particular, we first extract knowledge from semi-structured contents of vertical portals, fuse individual knowledge from each site, and further map them to a unified KB. The target DKB is then extracted from the overall KB based on a distance-based Expectation-Maximization (EM) algorithm. Results During the experiments, we selected eight popular vertical portals in China as data sources to construct DKB. There are 7703 instances and 96,041 edges in the final diabetes KB covering diseases, symptoms, western medicines, traditional Chinese medicines, examinations, departments, and body structures. The accuracy of DKB is 95.91%. Besides the quality assessment of extracted knowledge from vertical portals, we also carried out detailed experiments for evaluating the knowledge fusion performance as well as the convergence of the distance-based EM algorithm with positive results. Conclusions In this paper, we introduced an approach to constructing DKB. A knowledge extraction and fusion pipeline was first used to extract semi-structured data from vertical portals and individual KBs were further fused into a unified knowledge base. After that, we develop a distance based Expectation Maximization algorithm to extract a subset from the overall knowledge base forming the target DKB. Experiments showed that the data in DKB are rich and of high-quality.

Abstract The pathogenesis of steroid‐induced avascular necrosis of femoral head (SANFH) is complex, and there is a lack of effective early prevention method. The aim of the present study was to evaluate the effect of dexamethasone (DEX) on the biological behavior of bone marrow mesenchymal stem cells (BMSCs) and to explore the possibility of DEX in the clinical treatment of SANFH. The effect of DEX on the proliferation of BMSCs was evaluated by Counting Kit‐8 assay, western blot assay, and enzyme‐linked immunosorbent assay. Flow cytometry and western blot assay were performed to detect the effect of DEX on the apoptosis of BMSCs. Quantitative real‐time PCR and western blot assay were performed to detect the effect of DEX on the expression of endoplasmic reticulum stress (ERS)‐related genes. Immunoblotting analysis was conducted for detecting the nuclear‐cytoplasmic distribution of Nrf2. DEX could significantly inhibit the proliferation of BMSCs and promote apoptosis of BMSCs. DEX could increase the expression of PERK, ATF6, and IRE1a, and induce nuclear translocation of Nrf2. The addition of ML385 could reverse the effect of DEX on BMSCs. DEX could activate the PERK‐Nrf2 pathway to promote ERS and finally affect the cell proliferation and apoptosis of BMSCs.

Background: Osteosarcoma is the most leading primary malignancy of the bone in adolescents all over the world. Long non-coding RNA (lncRNA) 91 H has been reported to participated in multiple cancers. Meanwhile, lncRNA 91 H has been proved to be upregulated in osteosarcoma. However, the function of 91 H in osteosarcoma remains unclear. Methods: Gene and protein expressions in osteosarcoma cells were detected by qRT-PCR and western blot, respectively. Cell viability was tested by CCK-8 assay. Ki67 staining was used to measure cell proliferation. Cell apoptosis and cycle were assessed by flow cytometry. In addition, transwell assay was used to detect cell migration and invasion. Furthermore, Methylation-specific PCR (MSP) was performed to test the methylation of CDK4 promoter. Finally, xenograft mice model was established to explore the role of 91 H in osteosarcoma in vivo . Results: Knockdown of 91 H significantly inhibited the growth of osteosarcoma cells via inducing the cell apoptosis. In addition, 91 H siRNA notably suppressed the migration and invasion of osteosarcoma cells. Meanwhile, knockdown of 91 H inhibited the progression of osteosarcoma via inducing methylation of CDK4 promoter. Furthermore, 91 H knockdown obviously induced G1 arrest in osteosarcoma cells via inhibition of PCNA and Cyclin D1. Finally, knockdown of 91 H notably inhibited the tumor growth of osteosarcoma in vivo . Conclusion: knockdown of 91 H suppressed the tumorigenesis of osteosarcoma via inducing methylation of CDK4 promoter in vitro and in vivo . Thus, 91 H may serve as a new target for the treatment of osteosarcoma.

Impaired bone healing caused by severe trauma, infection, and tumor resection is an extremely common phenomenon. Therefore, the treatment of bone defects represents a major clinical challenge worldwide. In such situations, the application of biomaterials is necessary for filling defects and promoting bone regeneration. Bone repair biomaterials having osteoconductive and osteoinductive properties can act as an appropriate template for the formation of new bone and induce the osteogenic differentiation of preosteocytes and stem cells. Thus, the influence of biomaterials on the regulation of osteogenesis of mesenchymal stem cells (MSCs) has been widely studied. However, immune response is also critical in bone healing; macrophages play pivotal and dynamic roles in bone regeneration. The interfacial properties of biomaterials that affect the adsorption of proteins and the adhesion function of cells require great attention in the field of bone tissue engineering because they are related to the crosstalk with the immune and bone or stem cells. Thus, selection of biomaterials or specific surface coatings may reduce local undesirable inflammatory responses and promote bone regeneration. This review provides a detailed overview of bone regeneration mechanisms and the interaction between immune cells and MSCs. Moreover, the influence of biomaterials on the regulation of functions of MSCs and macrophages and the macrophage-related inflammatory response triggered by biomaterials and its specific role in osteogenesis are discussed.

Background and Purpose: Data on the relationship among neutrophil count, intracranial atherosclerotic stenosis (ICAS), and functional outcomes after endovascular thrombectomy (EVT) for ischemic stroke patients remains unclear. We aimed to evaluate the association between neutrophil count and prognosis of EVT patients and to determine whether the association was mediated by ICAS.Methods: We retrospectively analyzed consecutive patients who underwent EVT at two comprehensive stroke centers between June 2016 and December 2019. A remaining stenosis >70%, or a lesser degree of stenosis with a tendency toward re-occlusion or flow impairment during the procedure, was classified as ICAS. A poor outcome was defined as a 90-day modified Rankin Scale score of 3–6.Results: Of the 221 patients (mean age, 65.9 years; males, 61.1%) included in this study, 81 (36.3%) had ICAS, and 120 (54.3%) experienced a poor outcome at 90 days, respectively. In the multivariate adjustment for potential confounders, neutrophil count (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.04–1.36; P = 0.012) and presence of ICAS (OR, 2.65; 95CI%, 1.28–5.45; P = 0.008) were risk factors of poor outcomes. Furthermore, mediation analysis indicated that total ICAS mediated the association between increased neutrophil count and worse functional outcome after EVT (the regression coefficient was changed by 11.7% for poor outcome, and 17.1% for modified Rankin Scale score, respectively).Conclusions: Our study demonstrated that a higher neutrophil count might increase the risk of a poor outcome among ischemic stroke patients who underwent EVT, which was partially mediated by ICAS.

Abstract Assembling nanomaterials into hybrid structures provides a promising and flexible route to reach ultrahigh responsivity by introducing a trap‐assisted gain (G) mechanism. However, the high‐gain photodetectors benefitting from long carrier lifetime often possess slow response time (t) due to the inherent G–t tradeoff. Here, a light‐driven junction field‐effect transistor (LJFET), consisting of an n‐type ZnO belt as the channel material and a p‐type WSe2 nanosheet as a photoactive gate material, to break the G–t tradeoff through decoupling the gain from carrier lifetime is reported. The photoactive gate material WSe2 under illumination enables a conductive path for externally applied voltage, which modulates the depletion region within the ZnO channel efficiently. The gain and response time are separately determined by the field effect modulation and the switching speed of LJFET. As a result, a high responsivity of 4.83 × 103 A W−1 with a gain of ≈104 and a rapid response time of ≈10 µs are obtained simultaneously. The LJFET architecture offers a new approach to realize high‐gain and fast‐response photodetectors without the G–t tradeoff.

The insect-machine interface (IMI) is a novel approach developed for man-made air vehicles, which directly controls insect flight by either neuromuscular or neural stimulation. In our previous study of IMI, we induced flight initiation and cessation reproducibly in restrained honeybees (Apis mellifera L.) via electrical stimulation of the bilateral optic lobes. To explore the neuromechanism underlying IMI, we applied electrical stimulation to seven subregions of the honeybee brain with the aid of a new method for localizing brain regions. Results showed that the success rate for initiating honeybee flight decreased in the order: α-lobe (or β-lobe), ellipsoid body, lobula, medulla and antennal lobe. Based on a comparison with other neurobiological studies in honeybees, we propose that there is a cluster of descending neurons in the honeybee brain that transmits neural excitation from stimulated brain areas to the thoracic ganglia, leading to flight behavior. This neural circuit may involve the higher-order integration center, the primary visual processing center and the suboesophageal ganglion, which is also associated with a possible learning and memory pathway. By pharmacologically manipulating the electrically stimulated honeybee brain, we have shown that octopamine, rather than dopamine, serotonin and acetylcholine, plays a part in the circuit underlying electrically elicited honeybee flight. Our study presents a new brain stimulation protocol for the honeybee-machine interface and has solved one of the questions with regard to understanding which functional divisions of the insect brain participate in flight control. It will support further studies to uncover the involved neurons inside specific brain areas and to test the hypothesized involvement of a visual learning and memory pathway in IMI flight control.

Background The performance of intravenous tenecteplase in patients who had an acute ischaemic stroke with large/medium vessel occlusion or severe stenosis in an extended time window remains unknown. We investigated the promise of efficacy and safety of different doses of tenecteplase manufactured in China, in patients who had an acute ischaemic stroke with large/medium vessel occlusion beyond 4.5-hour time window.Methods The CHinese Acute tissue-Based imaging selection for Lysis In Stroke-Tenecteplase was an investigator-initiated, umbrella phase IIa, open-label, blinded-endpoint, Simon’s two-stage randomised clinical trial in 13 centres across mainland China. Participants who had salvageable brain tissue on automated perfusion imaging and presented within 4.5–24 hours from time of last seen well were randomised to receive 0.25 mg/kg tenecteplase or 0.32 mg/kg tenecteplase, both with a bolus infusion over 5–10 s. The primary outcome was proportion of patients with promise of efficacy and safety defined as reaching major reperfusion without symptomatic intracranial haemorrhage at 24–48 hours after thrombolysis. Assessors were blinded to treatment allocation. All participants who received tenecteplase were included in the analysis.Results A total of 86 patients who had an acute ischaemic stroke identified with anterior large/medium vessel occlusion or severe stenosis were included in this study from November 2019 to December 2021. All of the 86 patients enrolled either received 0.25 mg/kg (n=43) or 0.32 mg/kg (n=43) tenecteplase, and were available for primary outcome analysis. Fourteen out of 43 patients in the 0.25 mg/kg tenecteplase group and 10 out of 43 patients in the 0.32 mg/kg tenecteplase group reached the primary outcome, providing promise of efficacy and safety for both doses based on Simon’s two-stage design.Discussion Among patients with anterior large/medium vessel occlusion and significant penumbral mismatch presented within 4.5–24 hours from time of last seen well, tenecteplase 0.25 mg/kg and 0.32 mg/kg both provided sufficient promise of efficacy and safety.Trial registration number ClinicalTrials.gov Registry (NCT04086147, https://clinicaltrials.gov/ct2/show/NCT04086147).