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Abstract A lightweight fruit detection algorithm is important to ensure real‐time detection on low‐power computing devices while maintaining detection accuracy. In addition, the fruit detection algorithm is also faced with some environmental factors. To solve these challenges, lightweight detection algorithms termed YOLO‐Lite, YOLO‐Liter and YOLO‐Litest were developed based on the YOLOv5 framework. The compared mean average precision (mAP) detection revealed that YOLO‐Lite at 0.86 is 2%, 4%, 5%, 7%, and 16% more than YOLO‐Liter and YOLOv5n at 0.84 each, YOLOv4‐tiny at 0.82, YOLO‐Liter at 0.81, YOLO‐MobileNet at 0.79, and YOLO‐ShuffleNet at 0.70, respectively, but not for YOLOv8n at 0.87. On the Computer platform, except for YOLOv4‐tiny at 178.6 frames per second (FPS), the speed of YOLO‐Litest at 158.7 FPS is faster than YOLO‐Liter at 129.9 FPS, YOLO‐Lite at 120.5 FPS, YOLO‐ShuffleNet at 119.0 FPS, YOLOv8n at 116 FPS, YOLOv5n at 111.1 FPS, and YOLO‐MobileNet at 89.3 FPS. Using Jetson Nano, the 32.3 FPS of YOLO‐Litest is faster than other algorithms, but not YOLOv4‐tiny's 34.1 FPS. On the Raspberry Pi 4B, YOLO‐Litest with 4.69 FPS, outperformed other algorithms. The choices for an accurate and faster detection algorithm are YOLO‐Lite and YOLO‐Litest respectively, while YOLO‐Liter maintains a balance between them.

Abstract Herein, the feasibility of artificial black soil (ABS) derived from hydrothermal humification-hydrothermal carbonization (HTH-HTC) for restructuration of weak soil was verified. This study breaks through the long history of soil formation and evolution, and obtains reconstructed anthropogenic soil (AS) system which only takes one month, for the further application of rice seedlings. HTH-HTC derived by-products are slightly acidic, which facilitates the effective nutrient uptake and prevention of wilt diseases for acid-loving rice seedlings. AS mainly consists of the inherent components retained from weak soil such as SiO2 and minerals, and exogenous components such as artificial humic substances and hydrochar, as introduced by hydrothermal humification processes. Results exhibit that AS has high contents of ammonium nitrogen, organic matter, organic carbon, and abundant porous structure for nutrient transport and water holding, especially, the community diversity and richness of microbial system gets the expected recovery and new beneficial bacteria (such as Caballeronia calidae) or fungi (such as Humicola) appear. Positive effects of AS on agronomic traits in rice seedlings are quantified. As a general result, this study supports the application of AS in sustainable agriculture, and provides a novel strategy to tackle the already-omnipresent land degradation by anthropogenic misuse and larger scale accidents.

Mild thermal stimulation plays an active role in bone tissue repair and regeneration. In this work, a bioactive polydopamine/Ti3C2/poly(vinylidene fluoride trifluoroethylene) (PDA/Ti3C2/P(VDF-TrFE)) nanocomposite coating with excellent near-infrared light (NIR)-triggered photothermal effect was designed to improve the osteogenic ability of implants. By incorporating dopamine (DA)-modified Ti3C2 nanosheets into the P(VDF-TrFE) matrix and combining them with alkali initiated in situ polymerization, the resulting PDA/Ti3C2/P(VDF-TrFE) nanocomposite coating gained high adhesion strength on Ti substrate, excellent tribological and corrosion resistance properties, which was quite important for clinical application of implant coatings. Cell biology experiments showed that NIR-triggered mild thermal stimulation on the coating surface promoted cell spreading and growth of BMSCs, and also greatly upregulated the osteogenic markers, including Runt-Related Transcription Factor 2 (RUNX2), alkaline phosphatase (ALP), osteopontin (OPN), osteocalcin (OCN). Simultaneously, the synthesis of heat shock protein 47 (HSP47) was significantly promoted by the mild thermal stimulation, which strengthened the specific interaction between HSP47 and collagen Ⅰ (COL-Ⅰ), thereby activating the integrin-mediated MEK/ERK osteogenic differentiation signaling pathway. In addition, the results also showed that the mild thermal stimulation induced the polarization of macrophages towards M2 phenotype, which can attenuate the inflammatory response of injured bone tissue. Antibacterial results indicated that the coating exhibited an outstanding antibacterial ability against S. aureus and E. coli. Conceivably, the versatile implant bioactive coatings developed in this work will show great application potential for implant osseointegration.

Osseointegration commences with foreign body inflammation upon implant placement, where macrophages play a crucial role in the immune response. Subsequently, during the intermediate and late stages of osseointegration, mesenchymal stem cells (MSCs) migrate and initiate their osteogenic functions, while macrophages support MSCs in osteogenesis. The utilization of ferroelectric P(VDF-TrFE) covered ITO planar microelectrodes facilitated the simulation of various surface charge to investigate their effects on MSCs’ osteogenic differentiation and macrophage polarization and the results indicated a parabolic increase in the promotional effect of both with the rise in piezoelectric coefficient. Furthermore, the surface charge with a piezoelectric coefficient of −18 exhibited the strongest influence on the promotion of M1 polarization of macrophages and the promotion of MSCs’ osteogenic differentiation. The impact of macrophage polarization and MSC osteogenesis following the interaction of macrophages affected by surface charge and MSC was ultimately investigated. It was observed that macrophages affected by the surface charge of −18 piezoelectric coefficient still exerted the most profound induced osteogenic effect, validating the essential role of M1-type macrophages in the osteogenic differentiation of MSCs.

Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators (e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges, including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result, the design of new epigenetic modulators (e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging (HyT) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review, we aim to provide an in-depth illustration of new degrading strategies (2017–2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders.

Full-thickness skin wounds are have continued to be reconstructive challenges in dermal and skin appendage regeneration, and skin substitutes are promising tools for addressing these reconstructive procedures. Herein, the one-step fabrication of a cell sheet integrated with a biomimetic hydrogel as a tissue engineered skin for skin wound healing generated in one step is introduced. Briefly, cell sheets with rich extracellular matrix, high cell density, and good cell connections were integrated with biomimetic hydrogel to fabricate gel + human skin fibroblasts (HSFs) sheets and gel + human umbilical vein endothelial cells (HUVECs) sheets in one step for assembly as a cell sheet-laden hydrogel (CSH). The designed biomimetic hydrogel formed with UV crosslinking and ionic crosslinking exhibited unique properties due to the photo-generated aldehyde groups, which were suitable for integrating into the cell sheet, and ionic crosslinking reduced the adhesive force toward the substrate. These properties allowed the gel + cell sheet film to be easily released from the substrate. The cells in the harvested cell sheet maintained excellent viability, proliferation, and definite migration abilities inside the hydrogel. Moreover, the CSH was implanted into a full-thickness skin defects to construct a required dermal matrix and cell microenvironment. The wound closure rate reached 60.00 ± 6.26% on the 2nd day, accelerating mature granulation and dermis formation with skin appendages after 14 days. This project can provide distinct guidance and strategies for the complete repair and regeneration of full-thickness skin defects, and provides a material with great potential for tissue regeneration in clinical applications.

Toll-like receptor 2 (TLR2) mediated macrophages regulate the protective immune response to infectious microorganisms, but the aberrant activation of macrophages often leads to pathological inflammation, including tissue damage. In this study, we identified antagonists of TLR2 by screening 2100 natural products and subsequently identified Taspine, an aporphine alkaloid, as an excellent candidate. Furthermore, analysis of the 10 steps chemical synthesis route and structural optimization yielded the Taspine derivative SMU-Y6, which has higher activity, better solubility, and improved drug-feasible property. Mechanistic studies and seq-RNA analysis revealed that SMU-Y6 inhibited TLR2 over other TLRs, hindered the formation of TLR2/MyD88 complex, and blocked the downstream NF-κB and MAPK signaling pathway, thus suppressing the release of inflammatory cytokines. SMU-Y6 could stabilize TLR2 and bind to TLR2 protein with a Kd of 0.18 μmol/L. Additionally, SMU-Y6 could efficiently reverse the M1 phenotype macrophage polarization, reduce the production of cytokines as well as infiltration of neutrophiles and alleviate the local inflammation in mice with acute paw edema and colitis. Collectively, we reported the first aporphine alkaloid derivative that selectively inhibits TLR2 with high binding affinity and superior drug-feasible property, thus providing an urgently-needed molecular probe and potential drug candidate for inflammatory and autoimmune disease therapy.

Fe (hydr)oxides have a substantial impact on the structure and stability of soil organic carbon (SOC) pools and also drive organic carbon turnover processes via reduction–oxidation reactions. Currently, many studies have paid much attention to organic matter–Fe mineral–microbial interactions on SOC turnover, while there is few research on how exogenous carbon addition abiotically regulates the intrinsic mechanisms of Fe-mediated organic carbon conversion. The study investigated the coupling process of artificial humic acid (A-HA) and Fe(hydr)oxide, the mechanism of inner-sphere ligands, and the capacity for carbon sequestration using transmission electron microscopy, thermogravimetric, x-ray photoelectron spectroscopy, and wet-chemical disposal. Furthermore, spherical aberration-corrected scanning transmission electron microscopy–electron energy loss spectroscopy and Mössbauer spectra have been carried out to demonstrate the spatial heterogeneity of A-HA/Fe (hydr)oxides and reveal the relationship between the increase in Fe-phase crystallinity and redox sensitivity and the accumulation of organic carbon. Additionally, the dynamics of soil structures on a microscale, distribution of carbon–iron microdomains, and the cementing-gluing effect can be observed in the constructing nonliving anthropogenic soils, confirming that the formation of stable aggregates is an effective approach to achieving organic carbon indirect protection. We propose that exogenous organic carbon inputs, specifically A-HA, could exert a substantial but hitherto unexplored effect on the geochemistry of iron–carbon turnover and sequestration in anoxic water/solid soils and sediments.

Dynamic regulation of cell-extracellular matrix (ECM)-material interactions is crucial for various biomedical applications. In this study, a light-activated molecular switch for the modulation of cell attachment/detachment behaviors was established on monolayer graphene (Gr)/n-type Silicon substrates (Gr/Si). Initiated by light illumination at the Gr/Si interface, pre-adsorbed proteins (bovine serum albumin, ECM proteins collagen-1, and fibronectin) underwent protonation to achieve negative charge transfer to Gr films (n-doping) through π-π interactions. This n-doping process stimulated the conformational switches of ECM proteins. The structural alterations in these ECM interactors significantly reduced the specificity of the cell surface receptor-ligand interaction (e.g., integrin recognition), leading to dynamic regulation of cell adhesion and eventual cell detachment. RNA-sequencing results revealed that the detached bone marrow mesenchymal stromal cell sheets from the Gr/Si system manifested regulated immunoregulatory properties and enhanced osteogenic differentiation, implying their potential application in bone tissue regeneration. This work not only provides a fast and feasible method for controllable cells/cell sheets harvesting but also gives new insights into the understanding of cell-ECM-material communications.

Immunotherapy has led to a paradigm shift in the treatment of cancer. Current cancer immunotherapies are mostly antibody-based, thus possessing advantages in regard to pharmacodynamics (e.g., specificity and efficacy). However, they have limitations in terms of pharmacokinetics including long half-lives, poor tissue/tumor penetration, and little/no oral bioavailability. In addition, therapeutic antibodies are immunogenic, thus may cause unwanted adverse effects. Therefore, researchers have shifted their efforts towards the development of small molecule-based cancer immunotherapy, as small molecules may overcome the above disadvantages associated with antibodies. Further, small molecule-based immunomodulators and therapeutic antibodies are complementary modalities for cancer treatment, and may be combined to elicit synergistic effects. Recent years have witnessed the rapid development of small molecule-based cancer immunotherapy. In this review, we describe the current progress in small molecule-based immunomodulators (inhibitors/agonists/degraders) for cancer therapy, including those targeting PD-1/PD-L1, chemokine receptors, stimulator of interferon genes (STING), Toll-like receptor (TLR), etc. The tumorigenesis mechanism of various targets and their respective modulators that have entered clinical trials are also summarized.

An improved YOLOv5s model was proposed and validated on a new fruit dataset to solve the real-time detection task in a complex environment. With the incorporation of feature concatenation and an attention mechanism into the original YOLOv5s network, the improved YOLOv5s recorded 122 layers, 4.4 × 106 params, 12.8 GFLOPs, and 8.8 MB weight size, which are 45.5%, 30.2%, 14.1%, and 31.3% smaller than the original YOLOv5s, respectively. Meanwhile, the obtained 93.4% of mAP tested on the valid set, 96.0% of mAP tested on the test set, and 74 fps of speed tested on videos using improved YOLOv5s is 0.6%, 0.5%, and 10.4% higher than the original YOLOv5s model, respectively. Using videos, the fruit tracking and counting tested on the improved YOLOv5s observed less missed and incorrect detections compared to the original YOLOv5s. Furthermore, the aggregated detection performance of improved YOLOv5s outperformed the network of GhostYOLOv5s, YOLOv4-tiny, and YOLOv7-tiny, including other mainstream YOLO variants. Therefore, the improved YOLOv5s is lightweight with reduced computation costs, can better generalize against complex conditions, and is applicable for real-time detection in fruit picking robots and low-power devices.

Toll-like receptor 3 (TLR3), as an important pattern recognition receptor (PRR), dominates the innate and adaptive immunity regulating many acute and chronic inflammatory diseases. Atherosclerosis is proved as an inflammatory disease, and inflammatory events involved in the entire process of initiation and deterioration. However, the contribution of TLR3 to atherosclerosis remains unclear. Herein, we identified the clinical relevance of TLR3 upregulation and disease processes in human atherosclerosis. Besides, activation of TLR3 also directly led to significant expression of atherogenic chemokines and adhesion molecules. Conversely, silencing TLR3 inhibited the uptake of oxLDL by macrophages and significantly reduced foam cell formation. Given the aberrance in TLR3 functions on atherosclerosis progression, we hypothesized that TLR3 could serve as novel target for clinical atherosclerosis therapy. Therefore, we developed the novel ellipticine derivative SMU-CX24, which specifically inhibited TLR3 (IC50 = 18.87 ± 2.21 nmol/L). In vivo, atherosclerotic burden was alleviated in Western diet fed ApoE−/− mice in response to SMU-CX24 treatment, accompanying notable reductions in TLR3 expression and inflammation infiltration within atherosclerotic lesion. Thus, for the first time, we revealed that pharmacological downregulation of TLR3 with specific inhibitor regenerated inflammatory environment to counteract atherosclerosis progression, thereby proposing a new strategy and probe for atherosclerosis therapy.

The complex network topology, deployment unfriendliness, computation cost, and large parameters, including the natural changeable environment are challenges faced by fruit detection. Thus, a Simplified network topology for fruit detection, tracking and counting was designed to solve these problems. The network used common networks of Conv, Maxpool, feature concatenation and SPPF as new backbone and a modified decoupled head of YOLOv8 as head network. At the same time, it was validated on a dataset of images encompassing strawberry, jujube, and cherry fruits. Having compared to YOLO-mainstream variants, the params of Simplified network is 32.6%, 127%, and 50.0% lower than YOLOv5n, YOLOv7-tiny, and YOLOv8n, respectively. The results of mAP@50% tested using test-set show that the 82.4% of Simplified network is 0.4%, -0.2%, and 0.2% respectively more accurate than 82.0% of YOLOv5n, 82.6% of YOLOv7-tiny, and 82.2% of YOLOv8n. Furthermore, the Simplified network is 12.8%, 17.8%, and 11.8% respectively faster than YOLOv5n, YOLOv7-tiny, and YOLOv8n, including outperforming in tracking, counting, and mobile-phone deployment process. Hence, the Simplified network is robust, fast, accurate, easy-to-understand, fewer in parameters and deployable friendly.

Abstract Metal ions have been identified as important bone metabolism regulators and widely used in the field of bone tissue engineering, however their exact role during bone regeneration remains unclear. Herein, the aim of study was to comprehensively explore the interactions between osteoinductive and osteo-immunomodulatory properties of these metal ions. In particular, the osteoinductive role of zinc ions (Zn2+), as well as its interactions with local immune microenvironment during bone healing process, was investigated in this study using a sustained Zn2+ delivery system incorporating Zn2+ into β-tricalcium phosphate/poly(L-lactic acid) (TCP/PLLA) scaffolds. The presence of Zn2+ largely enhanced osteogenic differentiation of periosteum-derived progenitor cells (PDPCs), which was coincident with increased transition from M1 to M2 macrophages (M $$\varphi $$ φ s). We further confirmed that induction of M2 polarization by Zn2+ was realized via PI3K/Akt/mTOR pathway, whereas marker molecules on this pathway were strictly regulated by the addition of Zn2+. Synergically, this favorable immunomodulatory effect of Zn2+ further improved the osteogenic differentiation of PDPCs induced by Zn2+ in vitro. Consistently, the spontaneous osteogenesis and pro-healing osteoimmunomodulation of the scaffolds were thoroughly identified in vivo using a rat air pouch model and a calvarial critical-size defect model. Taken together, Zn2+-releasing bioactive ceramics could be ideal scaffolds in bone tissue engineering due to their reciprocal interactions between osteoinductive and immunomodulatory characteristics. Clarification of this synergic role of Zn2+ during osteogenesis could pave the way to develop more sophisticated metal-ion based orthopedic therapeutic strategies.

Abstract Lithium‐sulfur batteries attract lots of attention due to their high specific capacity, low cost, and environmental friendliness. However, the low sulfur utilization and short cycle life extremely hinder their application. Herein, we design and fabricate a three‐dimensional electrode by a simple filtration method to achieve a high‐sulfur loading. Biomass porous carbon is employed as a current collector, which not only enhances the electronic transport but also effectively limits the volume expansion of the active material. Meanwhile, an optimized carboxymethyl cellulose binder is chosen. The chemical bonding restricts the shuttle effect, leading to improved electrochemical performance. Under the ultrahigh sulfur load of 28 mg/cm2, the high capacity of 18 mAh/cm2 is still maintained, and stable cycling performance is obtained. This study demonstrates a viable strategy to develop promising lithium‐sulfur batteries with a three‐dimensional electrode, which promotes sulfur loading and electrochemical performance.

Abstract Sodium ion batteries and capacitors have demonstrated their potential applications for next-generation low-cost energy storage devices. These devices's rate ability is determined by the fast sodium ion storage behavior in electrode materials. Herein, a defective TiO2@reduced graphene oxide (M-TiO2@rGO) self-supporting foam electrode is constructed via a facile MXene decomposition and graphene oxide self-assembling process. The employment of the MXene parent phase exhibits distinctive advantages, enabling defect engineering, nanoengineering, and fluorine-doped metal oxides. As a result, the M-TiO2@rGO electrode shows a pseudocapacitance-dominated hybrid sodium storage mechanism. The pseudocapacitance-dominated process leads to high capacity, remarkable rate ability, and superior cycling performance. Significantly, an M-TiO2@rGO//Na3V2(PO4)3 sodium full cell and an M-TiO2@rGO//HPAC sodium ion capacitor are fabricated to demonstrate the promising application of M-TiO2@rGO. The sodium ion battery presents a capacity of 177.1 mAh g−1 at 500 mA g−1 and capacity retention of 74% after 200 cycles. The sodium ion capacitor delivers a maximum energy density of 101.2 Wh kg−1 and a maximum power density of 10,103.7 W kg−1. At 1.0 A g−1, it displays an energy retention of 84.7% after 10,000 cycles.

Abstract Natural extracellular matrices (ECMs) are three-dimensional (3D) and multi-scale hierarchical structure. However, coatings used as ECM-mimicking structures for osteogenesis are typically two-dimensional or single-scaled. Here, we design a distinct quasi-three-dimensional hierarchical topography integrated of density-controlled titania nanodots and nanorods. We find cellular pseudopods preferred to anchor deeply across the distinct 3D topography, dependently of the relative density of nanorods, which promote the osteogenic differentiation of osteoblast but not the viability of fibroblast. The in vivo experimental results further indicate that the new bone formation, the relative bone-implant contact as well as the push-put strength, are significantly enhanced on the 3D hierarchical topography. We also show that the exposures of HFN7.1 and mAb1937 critical functional motifs of fibronectin for cellular anchorage are up-regulated on the 3D hierarchical topography, which might synergistically promote the osteogenesis. Our findings suggest the multi-dimensions and multi-scales as vital characteristic of cell-ECM interactions and as an important design parameter for bone implant coatings.

Retinoic acid-inducible gene I (RIG-I) serves as an essential viral RNA sensor for innate immune. The activation of the RIG-I-like receptors (RLRs) pathway triggers many regulations for the outcome of type I interferon, including ubiquitination, dephosphorylation, ISGylation, and autophagy. However, the autophagy-related regulation of RIG-I is still not fully understood. To investigate the potentially unknown genes related to autophagy-related regulation of RIG-I, we firstly confirm the induction of autophagy derived by overexpression of RIG-I. Furthermore, the autophagy inducer and inhibitor drugs were used in different assays. The results showed autophagy could control the activation of RLRs pathway and expression of exogenous RIG-I. In addition, we carried out the transcriptome analysis of overexpression of RIG-I in vitro. Differentially expressed genes (DEGs) in GO and KEGG signaling pathways enrichment provided a newly complex network. Finally, the validation of qPCR indicated that the DEGs PTPN22, PRKN, OTUD7B, and SIRT2 were correlated to the negative regulation of excessive expression of RIG-I. Taken together, our study contributed new insights into a more comprehensive understanding of the regulation of excessive expression of RIG-I. It provided the potential candidate genes for autophagy-related negative regulation for further investigation.

Abstract Lithium/potassium ion capacitors (LICs/PICs) have been proposed to bridge the performance gap between high-energy batteries and high-power capacitors. However, their development is hindered by the choice, electrochemical performance, and preparation technique of the battery-type anode materials. Herein, a nitrogen and phosphorus dual-doped multilayer graphene (NPG) material is designed and synthesized through an arc discharge process, using low-cost graphite and solid nitrogen and phosphorus sources. When employed as the anode material, NPG exhibits high capacity, remarkable rate capability, and stable cycling performance in both lithium and potassium ion batteries. This excellent electrochemical performance is ascribed to the synergistic effect of nitrogen and phosphorus doping, which enhances the electrochemical conductivity, provides a higher number of ion storage sites, and leads to increased interlayer spacing. Full carbon-based NPG‖LiPF6‖active carbon (AC) LICs and NPG‖KPF6‖AC PICs are assembled and show excellent electrochemical performance, with competitive energy and power densities. This work provides a route for the large-scale production of dual-doped graphene as a universal anode material for high-performance alkali ion batteries and capacitors.

High specific surface area, reasonable pore structure and heteroatom doping are beneficial to enhance charge storage, which all depend on the selection of precursors, activators and reasonable preparation methods. Here, B, O and N codoped biomass-derived hierarchical porous carbon was synthesized by using KCl/ZnCl2 as a combined activator and porogen and H3BO3 as both boron source and porogen. Moreover, the cheap, environmentally friendly and heteroatom-rich laver was used as a precursor, and impregnation and freeze-drying methods were used to make the biological cells of laver have sufficient contact with the activator so that the layer was deeply activated. The as-prepared carbon materials exhibit high surface area (1514.3 m2 g−1), three-dimensional (3D) interconnected hierarchical porous structure and abundant heteroatom doping. The synergistic effects of these properties promote the obtained carbon materials with excellent specific capacitance (382.5 F g−1 at 1 A g−1). The symmetric supercapacitor exhibits a maximum energy density of 29.2 W h kg−1 at a power density of 250 W kg−1 in 1 M Na2SO4, and the maximum energy density can reach to 51.3 W h kg−1 at a power density of 250 W kg−1 in 1 M BMIMBF4/AN. Moreover, the as-prepared carbon materials as anode for lithium-ion batteries possess high reversible capacity of 1497 mA h g−1 at 1 A g−1 and outstanding cycling stability (no decay after 2000 cycles).

In this paper, we report the design, synthesis and biological evaluation of a novel S-allyl-l-cysteine (SAC) and gallic acid conjugate S-(4-fluorobenzyl)-N-(3,4,5-trimethoxybenzoyl)-l-cysteinate (MTC). We evaluate the effects on ischemia-reperfusion-induced PC12 cells, primary neurons in neonatal rats, and cerebral ischemic neuronal damage in rats, and the results showed that MTC increased SOD, CAT, GPx activity and decreased LDH release. PI3K and p-AKT protein levels were significantly increased by activating PI3K/AKT pathway. Mitochondrial pro-apoptotic proteins Bax and Bim levels were reduced while anti-apoptotic protein Bcl-2 levels were increased. The levels of cleaved caspase-9 and cleaved caspase-3 were also reduced in the plasma. The endoplasmic reticulum stress (ERS) was decreased, which in turns the survival rate of nerve cells was increased, so that the ischemic injury of neurons was protected accordingly. MTC activated the MEK-ERK signaling pathway and promoted axonal regeneration in primary neurons of the neonatal rat. The pretreatment of MEK-ERK pathway inhibitor PD98059 and PI3K/AKT pathway inhibitor LY294002 partially attenuated the protective effect of MTC. Using a MCAO rat model indicated that MTC could reduce cerebral ischemia-reperfusion injury and decrease the expression of proinflammatory factors. The neuroprotective effect of MTC may be due to inhibition of the over-activation of the TREK-1 channel and reduction of the current density of the TREK1 channel. These results suggested that MTC has a protective effect on neuronal injury induced by ischemia reperfusion, so it may have the potential to become a new type of neuro-ischemic drug candidate.

Abstract Toll‐like receptor 2 (TLR2) expressed on antigen presenting cells evokes a series of critical cytokines, which favor the development of tumor‐specific cytotoxic T lymphocytes (CTLs). Therefore, TLR2 represents an attractive cancer immunotherapeutic target. Here, a synthetic library of 14 000 compounds together with a series of newly developed compounds for NF‐κB activation using HEK‐Blue hTLR2 cells is initially screened. Following further screening in a variety of cells including HEK‐Blue hTLRs reporter cells, murine, and human macrophage cell lines, a potent small molecule agonist 23 (SMU‐Z1) is identified, which specifically activates TLR2 through its association with TLR1, with a EC50 of 4.88 ± 0.79 × 10−9 m. Toxicology studies, proinflammatory cytokines (e.g., TNF‐α, IL‐1β, IL‐6, and nitric oxide) and target‐protein based biophysical assays demonstrate the pharmacologically relevant characteristics of SMU‐Z1. In addition, SMU‐Z1 promotes murine splenocyte proliferation and upregulates the expression of CD8+ T cells, NK cells and DCs, which results in a significant antitumor effect in a murine leukemia model. Finally, the induced tumors in three out of seven mice disappear after administration of SMU‐Z1. Our studies thus identify a novel and potent TLR1/2 small molecule agonist, which displays promising immune adjuvant properties and antitumor immunity.

Safety is a significant evaluation index of rehabilitation medical devices and a significant precondition for practical application. However, the safety evaluation of cable-driven rehabilitation robots has not been reported, so this work aims to study the safety evaluation methods and evaluation index of cable-driven rehabilitation robots. A bionic muscle cable (BM cable) is proposed to construct a bionic muscle cable-driven lower limb rehabilitation robot (BM-CDLR). The working principle of the BM-CDLR is introduced. The safety performance factors are defined based on the mechanical analysis of the BM-CDLR. The structural safety evaluation index and the use safety evaluation index of the BM-CDLR are given by comprehensively considering the safety performance factors and a proposed speed influence function. The effect of the structural parameters of the elastic elements in the BM cable on the safety performance factors and safety of the BM-CDLR is analyzed and verified by numerical simulations and experimental studies. The results provide the basis for further study of the compliance control strategy and experiments of the human-machine interaction of the BM-CDLR.

Toll-like receptors (TLRs) activation enables host to recognize a large number of pathogen-associated molecule patterns (PAMPs), ignite immune cells to discriminate between self and non-self, and then promote the following innate and adaptive immune responses. Accumulated clinical/preclinical evidences have proven TLRs to be critical role in the autoimmune diseases, including inflammatory and tumor-associated diseases. Activation of TLRs is becoming or has been a target for cancer treatment. It is shown that TLRs can induce preferable anti-tumor effect by eliciting inflammatory cytokines expression and cytotoxic T lymphocytes (CTLs) response. As adjuvant, TLRs agonists can launch a strong immune response to assist cancer radiotherapy and bio-chemotherapy. On the other hand, tumor-associated antigens acting as PAMPs, can also activate TLRs and induce tumor gene-related programmed cell death, including apoptosis, autophagy and programmed necrosis. While there are also arguments that the excessive TLRs expression will promote tumor deterioration in various organisms, as the TLR-induced inflammation will accelerate the cancer cells boost in the tumor microenvironment (TME). However, the effect of TLRs acting on cancers is still not quite clear today. In this review, we will summarize the recent researches of TLRs in cancer treatment and their role in TME, giving a brief overview on future expectation.

It is well known that three-dimensional (3D) printing is an emerging technology used to produce customized implants and surface characteristics of implants, strongly deciding their osseointegration ability. In this study, Ti alloy microspheres were printed under selected rational printing parameters in order to tailor the surface micro-characteristics of the printed implants during additive manufacturing by an in situ, controlled way. The laser path and hatching space were responsible for the appearance of the stripy structure (S), while the bulbous structure (B) and bulbous–stripy composite surface (BS) were determined by contour scanning. A nano-sized structure could be superposed by hydrothermal treatment. The cytocompatibility was evaluated by culturing Mouse calvaria-derived preosteoblastic cells (MC3T3-E1). The results showed that three typical microstructured surfaces, S, B, and BS, could be achieved by varying the 3D printing parameters. Moreover, the osteogenic differentiation potential of the S, B, and BS surfaces could be significantly enhanced, and the addition of nano-sized structures could be further improved. The BS surface with nano-sized structure demonstrated the optimum osteogenic differentiation potential. The present research demonstrated an in situ, controlled way to tailor and optimize the surface structures in micro-size during the 3D printing process for an implant with higher osseointegration ability.

Electrochemical biosensors are essential for health monitors to help in diagnosis and detection of diseases. Enzyme adsorptions on biosensor electrodes and direct electron transfer between them have been recognized as key factors to affect biosensor performance. TiO2 has a good protein adsorption ability and facilitates having more enzyme adsorption and better electron transfer. In this work, Mg ions are introduced into TiO2 nanodots in order to further improve electrode performance because Mg ions are considered to have good affinity with proteins or enzymes. Mg doped TiO2 nanodots on Ti substrates were prepared by spin-coating and calcining. The effects of Mg doping on the nanodots morphology and performance of the electrodes were investigated. The density and size of TiO2 nanodots were obviously changed with Mg doping. The sensitivity of 2% Mg doped TiO2 nanodots based biosensor electrode increased to 1377.64 from 897.8 µA mM−1 cm−2 and its KMapp decreases to 0.83 from 1.27 mM, implying that the enzyme achieves higher catalytic efficiency due to better affinity of the enzyme with the Mg doped TiO2. The present work could provide an alternative to improve biosensor performances.

Soil and groundwater contamination has always been a global concern. Contaminants are migrated and transformed in the soil and groundwater environments, which in turn pose potential environmental risks to humans. This paper describes four typical contaminants, including heavy metals, polycyclic aromatic hydrocarbons, microplastics, and perfluorinated and polyfluoroalkyl substances. Based on a systematic summary of the sources, hazards, and migration behaviors of these four contaminants, various existing remediation methods are analyzed, and the advantages and disadvantages of different methods are discussed. Finally, the future research prospects of soil and groundwater remediation are described, and the significance of the study of contaminant migration and remediation in the subsurface environment is emphasized. This research can help to provide theoretical and technical support for the study of contaminant migration and removal in soil and groundwater environments, and further improve the removal rate in actual contaminant sites. [ABSTRACT FROM AUTHOR]