Transient simulation of the electrical hysteresis in a metal/polymer/metal nanostructure.

The time-dependent quantum transportation through a metal/polymer/metal system is theoretically investigated on the basis of a Su-Schrieffer-Heeger model combined with the hierarchical equations of motion formalism. Using a non-adiabatic dynamical method, the evolution of the electron subspace and lattice atoms with time can be obtained. It is found that the calculated transient currents vary with time and reach stable values after a response time under the bias voltages. However, the stable current as the system reaches its dynamical steady state exhibits a discrepancy between two sweep directions of the bias voltage, which results in pronounced electrical hysteresis loops in the current-voltage curve. By analyzing the evolution of instantaneous energy eigenstates, the occupation number of the instantaneous eigenstates, and the lattice of the polymer, we show that the formation of excitons and the delay of their annihilation are responsible for the hysteretic current-voltage characteristics, where electron-phonon interactions play the key factor. Furthermore, the hysteresis width and amplitude can also be modulated by the strength of the electron-phonon coupling, level-width broadening function, and temperature. We hope these results about past condition-dependent switching performance at a sweep voltage can provide further insight into some of the basic issues of interest in hysteresis processes in conducting polymers.

Hybridization and divergent climatic preferences drive divergence of two allopatric Gentiana species on the Qinghai-Tibet Plateau.

BACKGROUND AND AIMS: Exploring how species diverge is vital for understanding the drivers of speciation. Factors such as geographical separation and ecological selection, hybridization, polyploidization and shifts in mating system are all major mechanisms of plant speciation, but their contributions to divergence are rarely well understood. Here we test these mechanisms in two plant species, Gentiana lhassica and G. hoae, with the goal of understanding recent allopatric species divergence on the Qinghai-Tibet Plateau (QTP). METHODS: We performed Bayesian clustering, phylogenetic analysis and estimates of hybridization using 561 302 nuclear genomic single nucleotide polymorphisms (SNPs). We performed redundancy analysis, and identified and annotated species-specific SNPs (ssSNPs) to explore the association between climatic preference and genetic divergence. We also estimated genome sizes using flow cytometry to test for overlooked polyploidy. KEY RESULTS: Genomic evidence confirms that G. lhassica and G. hoae are closely related but distinct species, while genome size estimates show divergence occurred without polyploidy. Gentiana hoae has significantly higher average FIS values than G. lhassica. Population clustering based on genomic SNPs shows no signature of recent hybridization, but each species is characterized by a distinct history of hybridization with congeners that has shaped genome-wide variation. Gentiana lhassica has captured the chloroplast and experienced introgression with a divergent gentian species, while G. hoae has experienced recurrent hybridization with related taxa. Species distribution modelling suggested range overlap in the Last Interglacial Period, while redundancy analysis showed that precipitation and temperature are the major climatic differences explaining the separation of the species. The species differ by 2993 ssSNPs, with genome annotation showing missense variants in genes involved in stress resistance. CONCLUSIONS: This study suggests that the distinctiveness of these species on the QTP is driven by a combination of hybridization, geographical isolation, mating system differences and evolution of divergent climatic preferences.

Regulated Ion/Electron-Conducting Interphase Enables Stable Zinc-Metal Anodes for Aqueous Zinc-Ions Batteries.

Metallic Zinc (Zn) is considered as a remarkably promising anode for aqueous Zn-ion batteries due to its high volumetric capacity and low redox potential. Unfortunately, dendritic growth and severe side reactions destabilizes the electrode/electrolyte interface, and ultimately reduce the electrochemical performance. Here, an artificial protective layer (APL) with a regulated ion and electron-conducting interphase is constructed on the Zn-metal anode to provide excellent interfacial stability in high-rate cycling. The superior ionic and moderate electronic conductivity of the APL derives from the co-embedding of MXene and Zn(CF3 SO3 )2 salts into the polyvinyl alcohol hydrogel, which enables a synergistic effect of local current density reduction during plating and ion transport acceleration during stripping for Zn anode. Furthermore, the high Young's modulus of the protective layer and dendrite-free deposition morphology during cycling suppresses hydrogen evolution reactions (2.5 mmol h-1 cm-2 ) and passivation. As a result, in symmetrical cell tests, the modified battery presents a stable life of over 2000 cycles at ultra-high current density of 20 mA cm-2 . This research presents a new insight into the formation and regulation of stable electrode-electrolyte interface for the Zn-metal anode.

A Biomimetic Nanogenerator of Reactive Nitrogen Species Based on Battlefield Transfer Strategy for Enhanced Immunotherapy.

Currently, cell membrane is always utilized for the construction of biomimetic nanoparticles. By contrast, mimicking the intracellular activity seems more meaningful. Inspired by the specific killing mechanism of deoxy-hemoglobin (Hb) dependent drug (RRx-001) in hypoxic red blood cells (RBC), this work aims to develop an inner and outer RBC-biomimetic antitumor nanoplatform that replicates both membrane surface properties and intracellularly certain therapeutic mechanisms of RRx-001 in hypoxic RBC. Herein, RRx-001 and Hb are introduced into RBC membrane camouflaged TiO2 nanoparticles. Upon arrival at hypoxic tumor microenvironment (TME), the biomimetic nanoplatform (R@HTR) is activated and triggers a series of reactions to generate reactive nitrogen species (RNS). More importantly, the potent antitumor immunity and immunomodulatory function of RNS in TME are demonstrated. Such an idea would transfer the battlefield of RRx-001 from hypoxic RBC to hypoxic TME, enhancing its combat capability. As a proof of concept, this biomimetic nanoreactor of RNS exhibits efficient tumor regression and metastasis prevention. The battlefield transfer strategy would not only present meaningful insights for immunotherapy, but also realize substantial breakthroughs in biomimetic nanotechnology.

Berberine Targets PKM2 to Activate the t-PA-Induced Fibrinolytic System and Improves Thrombosis.

BACKGROUND: Arterial thrombosis, a condition in which thrombi form in arteries, can lead to various acute cardiovascular diseases and impact the quality of life and survival of patients. Berberine (BBR), a quaternary ammonium alkaloid, has been shown to treat these diseases. However, further exploration is needed to understand underlying mechanisms of BBR. METHODS AND RESULTS: Rats were administered BBR via intramuscular injection. Then, an FeCl3-coated filter paper was applied to a carotid artery to induce thrombosis. The size of the thrombus and the blood flow velocity were evaluated by carotid ultrasound. The shape of the thrombus was observed using staining and microscopy. The expression levels of mRNA and proteins were verified. Additionally, mass spectrometry and single-cell RNA sequencing analysis were conducted. The administration of BBR resulted in a significant reduction in the thrombus area and an extension of the thrombus-clogging time. Furthermore, BBR administration effectively reversed the decreasing tissue-plasminogen activator (t-PA) expression and alterations in fibrinolysis system of model group. Additionally, the expression of PKM2 was suppressed following BBR administration, and the overexpression of PKM2 inhibited t-PA expression. CONCLUSIONS: BBR ameliorates thrombosis by modulating expression of PKM2, subsequently impacting the expression of t-PA within fibrinolytic system. These preliminary findings suggest that BBR could be a potential preventive and therapeutic strategy for arterial thromboembolic diseases.

A metabolic intervention strategy to break evolutionary adaptability of tumor for reinforced immunotherapy.

The typical hallmark of tumor evolution is metabolic dysregulation. In addition to secreting immunoregulatory metabolites, tumor cells and various immune cells display different metabolic pathways and plasticity. Harnessing the metabolic differences to reduce the tumor and immunosuppressive cells while enhancing the activity of positive immunoregulatory cells is a promising strategy. We develop a nanoplatform (CLCeMOF) based on cerium metal-organic framework (CeMOF) by lactate oxidase (LOX) modification and glutaminase inhibitor (CB839) loading. The cascade catalytic reactions induced by CLCeMOF generate reactive oxygen species "storm" to elicit immune responses. Meanwhile, LOX-mediated metabolite lactate exhaustion relieves the immunosuppressive tumor microenvironment, preparing the ground for intracellular regulation. Most noticeably, the immunometabolic checkpoint blockade therapy, as a result of glutamine antagonism, is exploited for overall cell mobilization. It is found that CLCeMOF inhibited glutamine metabolism-dependent cells (tumor cells, immunosuppressive cells, etc.), increased infiltration of dendritic cells, and especially reprogrammed CD8+ T lymphocytes with considerable metabolic flexibility toward a highly activated, long-lived, and memory-like phenotype. Such an idea intervenes both metabolite (lactate) and cellular metabolic pathway, which essentially alters overall cell fates toward the desired situation. Collectively, the metabolic intervention strategy is bound to break the evolutionary adaptability of tumors for reinforced immunotherapy.

Establishing Thermal Infusion Method for Stable Zinc Metal Anodes in Aqueous Zinc-Ion Batteries.

Metallic zinc (Zn) having low cost, high capacity, environmentally friendly features is considered to be an attractive anode material for aqueous energy storage devices. However, dendritic growth and severe side reactions restrict the development of Zn-metal anodes. Numerous 3D hosts are extensively explored to settle these issues, whereas the accessible prestoring of Zn metal into structured electrodes is challenging. Here, a thermal infusion strategy is first reported to create a stable composite Zn-based anode. Upon this melting-wetting-cooling process, the metallic Zn is densely and firmly encapsulated in the 3D skeleton, efficiently inhibiting the dendritic growth. Meanwhile, through in/ex situ tests, the formation of ZnO layer on the metallic Zn surface inhibits the hydrogen evolution reactions (1.8 mmol h-1 cm-2 ) and passivation during cycling. Consequently, the electrode enables a long-cycling life of over 1000 cycles at 10 mA cm-2 in a symmetrical cell. The pouch cells pairing this novel anode and LiMn2 O4 cathode maintain over 94 mAh g-1 capacity retention after 300 cycles. This research presents an innovative Zn anode structure and extendable prestoring metallic Zn method for aqueous Zn-ion batteries.

Encapsulation of Metallic Zn in a Hybrid MXene/Graphene Aerogel as a Stable Zn Anode for Foldable Zn-Ion Batteries.

A 3D host can effectively mitigate the dendritic growth of a zinc (Zn)-metal anode. However, the increased electrode/electrolyte reaction area using the 3D substrate accelerates the passivation and corrosion at the anode interface, ultimately degrading the electrochemical performance. Here, an oriented freezing process is used to create a flexible MXene/graphene scaffold. Based on the abundant zincophilic traits and micropores in the structure, Zn is densely encapsulated inside the host by the electrodeposition process. During cycling, the composite anode endows an in situ solid electrolyte interface with zinc fluoride at the electrode/electrolyte interface due to inherent fluorine terminations in MXene, efficiently inhibiting the dendritic growth. Furthermore, the design wherein bulk Zn is distributed in a 3D microscale manner suppresses hydrogen evolution reactions (3.8 mmol h-1 cm-2 ) and passivation, through in/ex situ tests. As a result, in a symmetrical cell test, the electrode has a long-cycling life of over 1000 h at 10 mA cm-2 . After continuous single folding followed by double folding, a quasi-solid-state foldable cell with the composite anode and a LiMn2 O4 cathode (60% depth of discharge) maintains high-capacity retention of over 91%. This research presents a revolutionary encapsulating idea for aqueous Zn-ion batteries, as well as foldable investigation.

Bimetallic Antimony-Vanadium Oxide Nanoparticles Embedded in Graphene for Stable Lithium and Sodium Storage.

Bimetallic oxides have received considerable attention as anodes for lithium/sodium-ion batteries (LIBs/SIBs) due to their high electrochemical activity and theoretical specific capacity. However, their cycling performance is limited by large volume variation, severe aggregation, and pulverization of bimetallic oxide nanoparticles during repeated metal ion insertion/extraction processes. Herein, bimetallic antimony-vanadium oxide nanoparticles embedded in graphene (SbVO4/G) composites are prepared by a one-step hydrothermal method. Bimetallic SbVO4 with abundant redox reaction sites can provide high specific capacity by a multi-electron reaction. A robust graphene substrate can not only alleviate volume expansion but also prevent aggregation and collapse of highly active bimetallic SbVO4. Due to the excellent synergy between the two building components, SbVO4/G hybrids exhibit excellent electrochemical activity, structural stability, and electrochemical performance. When employed as anodes for LIBs and SIBs, SbVO4/G composites display excellent cycling performance (1079.5 mAh g-1 at 0.1 A g-1 after 150 cycles for LIBs and 401.6 mAh g-1 at 0.1 A g-1 after 450 cycles for SIBs) and impressive rate capability. This work demonstrates that SbVO4/G composites are promising anodes for both LIBs and SIBs.

Cascade Catalytic Nanoplatform Based on "Butterfly Effect" for Enhanced Immunotherapy.

The unique tumor microenvironment (TME) characteristics such as immunosuppression impeded traditional cancer treatments. In contrast, developing cascade catalytic nanoplatforms by fully making use of substances in TME for cancer therapy may deserve full credit. Herein, a cascade catalytic nanoplatform based on glucose oxidase (GOD) modified mesoporous iron oxide nanoparticles (IONP) loaded with Artemisinin (ART) is developed, which is designed as IONP-GOD@ART. GOD can catalyze the oxidization of glucose into gluconic acid and H2 O2 , which not only realizes tumor starvation therapy, but also provides H2 O2 for IONP mediated Fenton reaction. Simultaneously, mesoporous IONP releases Fe2+ and Fe3+ ions in acidic TME. On the one hand, iron ions undergo Fenton reaction to generate hydroxyl radicals for chemodynamic therapy. On the other hand, the endoperoxide bridge in ART is broken in presence of Fe2+ and further generates reactive oxygen species (ROS) to achieve therapeutic purpose. In this sense, IONP-GOD@ART manipulates TME characteristics and leads to "butterfly effect", which brings out a large amount of ROS for eliciting immunogenic cell death, inducing M1-TAMs polarization, and further reprogramming immunosuppressive TME for enhanced immunotherapy. By this delicate design, the cascade catalytic nanoplatform of IONP-GOD@ART realizes potent cancer immunotherapy for tumor regression and metastasis prevention.

Ultrathin Surface Coating of Nitrogen-Doped Graphene Enables Stable Zinc Anodes for Aqueous Zinc-Ion Batteries.

Owing to the high volumetric capacity and low redox potential, zinc (Zn) metal is considered to be a remarkably prospective anode for aqueous Zn-ion batteries (AZIBs). However, dendrite growth severely destabilizes the electrode/electrolyte interface, and accelerates the generation of side reactions, which eventually degrade the electrochemical performance. Here, an artificial interface film of nitrogen (N)-doped graphene oxide (NGO) is one-step synthesized by a Langmuir-Blodgett method to achieve a parallel and ultrathin interface modification layer (≈120 nm) on Zn foil. The directional deposition of Zn crystal in the (002) planes is revealed because of the parallel graphene layer and beneficial zincophilic-traits of the N-doped groups. Meanwhile, through the in situ differential electrochemical mass spectrometry and in situ Raman tests, the directional plating morphology of metallic Zn at the interface effectively suppresses the hydrogen evolution reactions and passivation. Consequently, the pouch cells pairing this new anode with LiMn2 O4 cathode maintain exceptional energy density (164 Wh kg-1 after 178 cycles) at a reasonable depth of discharge, 36%. This work provides an accessible synthesis method and in-depth mechanistic analysis to accelerate the application of high-specific-energy AZIBs.

Cascade catalytic nanoplatform based on ions interference strategy for calcium overload therapy and ferroptosis.

Intracellular ions played prominent part in cell function and behavior. Disrupting intracellular ions homeostasis might switch ions signal from "regulating" to "destroying". Inspired by this, we introduced the ions interference strategy for tumor therapy. Herein, curcumin (CUR) and transferrin (Tf) co-loaded calcium peroxide nanoparticles (CaO2 NPs) were formulated. With tumor targeting ability, CaO2/Tf/CUR pinpointed tumor cells and then instantaneously decomposed in acidic lysosomes, concurrently accompanying with the release of Ca2+ and CUR, as well as the production of H2O2. Then H2O2 not only damaged structure of Tf to release Fe3+, but also was converted to hydroxyl radicals via ferric ions mediated Fenton reaction for ferroptosis. In addition, the released Ca2+ and CUR induced Ca2+ overload via exogenous and endogenous calcium ions accumulation, respectively, further activating mitochondria apoptosis signaling pathway for cell injury. Therefore, based on calcium and ferric ions interference strategy, the cascade catalytic CaO2/Tf/CUR offered synergistic combination of ferroptosis, Ca2+ overload therapy and chemotherapy, which held a great promise in cancer treatment.

Biomimetic Ca2+ nanogenerator based on ions interference strategy for tumour-specific therapy.

Intracellular Ca2+ ions as second messenger played key role in cell behaviour, which was often overlooked in traditional antitumor treatment. Disrupting Ca2+ ion homeostasis by Ca2+ overload might switch ions signal from 'regulating' to 'destroying'. Inspired by this, a biomimetic Ca2+ nanogenerator was constructed. Briefly, the curcumin (CUR) was loaded into mesoporous calcium carbonate nanoparticles (MCC NPs), and then coated with platelet (PLT) membrane. Upon reaching tumour cells by PLT membrane-mediated tumour targeting effect, PLT@MCC/CUR would instantaneously decompose in acidic lysosomes, concurrently accompanying with Ca2+ generation and CUR release. The CUR could further facilitate Ca2+ release from endoplasmic reticulum (ER) and inhibit Ca2+ efflux, aggravating Ca2+ overload to disrupt mitochondrial Ca2+ homeostasis for mitochondria apoptosis signalling pathway activation. Interestingly, such effect was ineffective in normal cells, realising the tumour-specific therapeutic therapy. Based on ions interference strategy, PLT@MCC/CUR herein offered synergistic combination of Ca2+ overload therapy and chemotherapy, which would pave the way towards more effective nanotherapeutics.

The role of the JAK2-STAT3 pathway in pro-inflammatory responses of EMF-stimulated N9 microglial cells.

BACKGROUND: In several neuropathological conditions, microglia can become overactivated and cause neurotoxicity by initiating neuronal damage in response to pro-inflammatory stimuli. Our previous studies have shown that exposure to electromagnetic fields (EMF) activates cultured microglia to produce tumor necrosis factor (TNF)-α and nitric oxide (NO) through signal transduction involving the activator of transcription STAT3. Here, we investigated the role of STAT3 signaling in EMF-induced microglial activation and pro-inflammatory responses in more detail than the previous study. METHODS: N9 microglial cells were treated with EMF exposure or a sham treatment, with or without pretreatment with an inhibitor (Pyridone 6, P6) of the Janus family of tyrosine kinases (JAK). The activation state of microglia was assessed via immunoreaction using the microglial marker CD11b. Levels of inducible nitric oxide synthase (iNOS), TNF-α and NO were measured using real-time reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA) and the nitrate reductase method. Activation of JAKs and STAT3 proteins was evaluated by western blotting for specific tyrosine phosphorylation. The ability of STAT3 to bind to DNA was detected with an electrophoresis mobility shift assay (EMSA). RESULTS: EMF was found to significantly induce phosphorylation of JAK2 and STAT3, and DNA-binding ability of STAT3 in N9 microglia. In addition, EMF dramatically increased the expression of CD11b, TNF-α and iNOS, and the production of NO. P6 strongly suppressed the phosphorylation of JAK2 and STAT3 and diminished STAT3 activity in EMF-stimulated microglia. Interestingly, expression of CD11b as well as gene expression and production of TNF-α and iNOS were suppressed by P6 at 12 h, but not at 3 h, after EMF exposure. CONCLUSIONS: EMF exposure directly triggers initial activation of microglia and produces a significant pro-inflammatory response. Our findings confirm that the JAK2-STAT3 pathway may not mediate this initial microglial activation but does promote pro-inflammatory responses in EMF-stimulated microglial cells. Thus, the JAK2-STAT3 pathway might be a therapeutic target for reducing pro-inflammatory responses in EMF-activated microglia.

[Relationship between activation of microglia and Jaks phosphorylation induced by microwave irradiation].

OBJECTIVE: To explore the relationship between microglial proinflammatory and electromagnetic radiation and unveil the role of microglia in microwave radiation induced central nervous system injury. METHODS: N9 microglia cells cultured in vitro were exposed to microwave at 90 mW/cm2. Cell flow cytometry was used to observe the expression of CD11b at different time points after exposure; ELISA was used to detect the concentration of TNF-alpha in N9 cell culture supernatant; RT-PCR analysis confirmed iNOS mRNA expression in N9 microglia cells; and Nitrate Reductase Method was used to test NO amount in culture supernatant. RESULTS: The CD11b positive microglial cells increased significantly at 3 h after microwave exposure (P < 0.05), continued to increase until 24 h and peaked at 6 h after exposure. The amount of TNF-alpha rose dramatically from 1 h to 24 h after exposure (P < 0.01) and peaked at 3 h [(762.1 +/- 61.5) pg/ml] after exposure (P < 0.01). The level of NO started to increase at 1 h [(4.48-0.59) micromol/L] and lasted for 24 h after exposure. The expression of iNOS mRNA increased significantly at 1 h (P < 0.05), and tripled the original expression at 6 h after exposure, hereafter, it decreased slightly, but all were higher than the control group within 24 h after exposure. CONCLUSION: Microwave radiation could induce the activation of microglia cells. The activated microglia cells could induce microglial proinflammatory by producing large amounts of TNF-alpha, NO, etc.

PPy nanoneedle based nanoplatform capable of overcoming biological barriers for synergistic chemo-photothermal therapy.

The biological barriers in vivo have limited the site-specific bioavailability and impeded therapeutic efficacy. To tackle these issues, nonspherical particles with a shape effect have attracted wide attention to affect the in vivo translocation of a drug delivery system. Herein, we constructed a nanoplatform based on polypyrrole (PPy) nanoneedles by hyaluronic acid (HA) modification and doxorubicin (DOX) loading. The PPy-HA@DOX nanoneedles with high aspect ratios could enhance the extravasation through the fenestrated vasculature of tumors, transport across tumor cell membrane via an endocytosis mechanism or even penetrated the membrane directly, and ultimately enter the nucleus easily via the nuclear pore complex by passive diffusion. With the ability of overcoming biological barriers, the PPy nanoneedle based nanoplatform would deliver drugs into the organelles more effectively. Under near infrared (NIR) laser irradiation, PPy as the photothermal agent could lead to tumor cellular structure damage for photothermal therapy (PTT). Therefore, PPy-HA@DOX developed here would exploit the merits of synergistic combination of chemo-photothermal therapy, which would pave the way toward more effective nanotherapeutics.

[Effects of occupational microwave irradiation on heat shock protein 70 expressions in rat hippocampus].

OBJECTIVE: To study the change of heat shock protein (HSP)70 expression after exposure to occupational microwave in rats hippocampus, and explore the role of HSP70 in the mechanism of bio-effect of microwave irradiation. METHODS: The animal model was established by whole body exposures in 90, 5 W/cm(2) microwave irradiation field for 20 min in rats. Changes of the mRNA of hsp70 expressions in rat hippocampus at different time were studied by RT-PCR, and the protein change by Western blot. RESULTS: The mRNA and protein expression of hsp70 in rat hippocampus increased after 90 W/cm(2) and 5 W/cm(2) microwave irradiation for 20 min. The anal temperature and the value of SAR increased significantly. These changes were positively correlated with power and irradiation time of microwave. The results indicated that microwave irradiation led to HSP70 syntheses effectively. CONCLUSION: Microwave irradiation can obviously induce the thermal effect and activate HSP70, and initiate the endogenous protective mechanism of central nervous system.

Cancer Cell Membrane-Biomimetic Nanoplatform for Enhanced Sonodynamic Therapy on Breast Cancer via Autophagy Regulation Strategy.

Autophagy was considered as a double-edged sword that might cooperate, aggravate, or antagonize apoptosis. We found that the sonodynamic therapy (SDT) in low dosage induced autophagy and might function as a survival pathway for breast cancer and exhibit resistance to SDT-mediated apoptosis. In this sense, it was highly desired to enhance SDT via autophagy regulation strategy. Herein, we reported a biomimetic nanoplatform based on hollow mesoporous titanium dioxide nanoparticles (HMTNPs) by autophagy inhibitor (hydroxychloroquine sulphate, HCQ) loading and cancer cell membrane (CCM) coating. Owing to the biomimetic surface functionalization, the CCM-HMTNPs/HCQ could escape from macrophage phagocytosis, actively recognize and home in on the tumor by homologous targeting ability. Afterward, the released HCQ in response to the ultrasound stimulus was capable of blocking the autophagic flux and cutting off the nutrients supply derived from the damaged organelles, which was anticipated to abrogate the cells' resistance to SDT. Meanwhile, the vessel normalization effect of HCQ alleviated the tumor hypoxia, which was bound to enhance the oxygen-dependent HMTNPs-mediated SDT treatment. Based on the above findings, it was undoubtedly logical that CCM-HMTNPs/HCQ would sensitize breast cancer cells to SDT via autophagy regulation strategy, which held a great promise in cancer treatment.

Hypoxia enhances CXCR4 expression favoring microglia migration via HIF-1alpha activation.

Migration toward pathological area is the first critical step in microglia engagement during the central nervous system (CNS) injury, although the molecular mechanisms underlying microglia mobilization have not been fully understood. Here, we report that hypoxia promotes stromal cell-derived factor-1alpha (SDF-1alpha) induced microglia migration by inducing the CXC chemokine receptor 4 (CXCR4) expression. Exposure to hypoxia significantly enhanced CXCR4 expression levels in N9 microglia cell. Then, cell migration induced by SDF-1, a CXCR4-specific ligand, was observed accelerated. Blockade of hypoxia inducible factor-1alpha (HIF-1alpha) activation by inhibitors of phosphoinositide-3-kinase (PI3K)/Akt signaling pathway abrogated both of hypoxia-induced CXCR4 up-regulation and cell-migration acceleration. These results point to a crucial role of Hypoxia-HIF-1alpha-CXCR4 pathway during microglia migration.

A signal-decreased electrochemical immunosensor for the sensitive detection of LAG-3 protein based on a hollow nanobox-MOFs/AuPt alloy.

In this work, hollow nanobox metal-organic framework (HNM) nanocomposites were synthesised and utilised for the first time in a signal decreased electrochemical immunosensor for the ultrasensitive quantitative determination of lymphocyte activation gene-3 (LAG-3) protein, which is a newly discovered biomarker. With the aid of signal materials, namely, SiO2-tagged anti-LAG-3 antibody (SiO2-Ab2) and the biotin-streptavidin system, the sensor can achieve signal amplification. Encapsulation of tin dioxide-functionalised reduced graphene oxide (rGO-SnO2) and gold and platinum alloys (AuPt alloys) onto the surface of hollow nanobox metal-organic frameworks (MOFs) was performed to prepare rGO-SnO2/hollow nanobox-MOFs/AuPt alloys (rGO-SnO2/HNMs/AuPt) as the matrix. SiO2-Ab2, which is used as the signal-decreased label, can be utilised to enhance the distinction of the electrochemical signal after the specific recognition between antibodies and antigens, owing to its large steric hindrance property. In this sensor, this proposed sandwich immunosensor can achieve a high sensitivity, especially in the presence of low concentrations of the LAG-3 protein. Under optimal conditions, this sandwich-designed immunosensor exhibited a sensitive detection of the LAG-3 protein from concentrations of 0.01 ng mL-1 to 1 µg mL-1, with a lower detection limit of 1.1 pg mL-1 (based on 3σ). We proposed that this ultrasensitive biosensor can be utilised for the detection of the LAG-3 protein in early clinical tumour diagnosis.