High-dose dexamethasone regulates microglial polarization via the GR/JAK1/STAT3 signaling pathway after traumatic brain injury

Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently understood.As potent anti-inflammato ry agents,the use of glucoco rticoids in traumatic brain injury is still controversial,and their regulatory effects on microglial polarization are not yet known.In the present study,we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of action.In vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial polarization.Lipopolysaccharide,dexamethasone,RU486(a glucocorticoid receptor antagonist),and ruxolitinib(a Janus kinase 1 antagonist)were administered.RNA-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of dexamethasone.The Morris water maze,quantitative reverse transcription-polymerase chain reaction,western blotting,immunofluorescence and confocal microscopy analysis,and TUNEL,Nissl,and Golgi staining were performed to investigate our hypothesis.High-throughput sequencing results showed that arginase 1,a marker of M2 microglia,was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at3 days post-traumatic brain injury.Thus dexamethasone inhibited M1 and M2 microglia,with a more pronounced inhibitory effect on M2microglia in vitro and in vivo.Glucocorticoid receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain injury.Additionally,glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death,and also decreased the density of dendritic spines.A possible downstream receptor signaling mechanism is the GR/JAK1/STAT3 pathway.Overactivation of glucocorticoid receptor by high-dose dexamethasone reduced the expression of M2 microglia,which plays an antiinflammatory role.In contrast,inhibiting the activation of glucocorticoid receptor reduced the number of apoptotic glia and neurons and decreased the loss of dendritic spines after traumatic brain injury.Dexamethasone may exe rt its neurotoxic effects by inhibiting M2 microglia through the GR/JAK1/STAT3 signaling pathway.

Highly Thermoconductive,Strong Graphene‑Based Composite Films by Eliminating Nanosheets Wrinkles

Graphene-based thermally conductive composites have been proposed as effective thermal management materials for cooling high-power electronic devices.However,when flexible graphene nanosheets are assembled into macroscopic thermally conductive composites,capillary forces induce shrinkage of graphene nanosheets to form wrinkles during solution-based spontaneous drying,which greatly reduces the thermal conductivity of the composites.Herein,graphene nanosheets/aramid nanofiber(GNS/ANF)composite films with high thermal conductivity were prepared by in-plane stretching of GNS/ANF composite hydrogel networks with hydrogen bonds andπ-πinteractions.The in-plane mechanical stretching eliminates graphene nanosheets wrinkles by suppressing inward shrinkage due to capillary forces during drying and achieves a high in-plane orientation of graphene nanosheets,thereby creating a fast in-plane heat transfer channel.The composite films(GNS/ANF-60 wt%)with eliminated graphene nanosheets wrinkles showed a significant increase in thermal conductivity(146 W m^(−1)K^(−1))and tensile strength(207 MPa).The combination of these excellent properties enables the GNS/ANF composite films to be effectively used for cooling flexible LED chips and smartphones,showing promising applications in the thermal management of high-power electronic devices.

Biomass-enhanced Janus sponge-like hydrogel with salt resistance and highstrength for efficient solar desalination

Interfacial solar-driven evaporation technology shows great potential in the field of industrial seawater desalination, and the development ofefficient and low-cost evaporation materials is key to achieving large-scale applications. Hydrogels are considered to be promising candidates;however, conventional hydrogel-based interfacial solar evaporators have difficulty in simultaneously meeting multiple requirements, including ahigh evaporation rate, salt resistance, and good mechanical properties. In this study, a Janus sponge-like hydrogel solar evaporator (CPAS) withexcellent comprehensive performance was successfully constructed. The introduction of biomass agar (AG) into the polyvinyl alcohol (PVA)hydrogel backbone reduced the enthalpy of water evaporation, optimized the pore structure, and improved the mechanical properties. Meanwhile, by introducing hydrophobic fumed nano-silica aerogel (SA) and a synergistic foaming-crosslinking process, the hydrogel spontaneouslyformed a Janus structure with a hydrophobic surface and hydrophilic bottom properties. Based on the reduction of the evaporation enthalpy andthe modulation of the pore structure, the CPAS evaporation rate reached 3.56 kg m^(-2) h^(-1) under one sun illumination. Most importantly, owingto the hydrophobic top surface and 3D-interconnected porous channels, the evaporator could work stably in high concentrations of salt-water(25 wt% NaCl), showing strong salt resistance. Efficient water evaporation, excellent salt resistance, scalable preparation processes, and low-costraw materials make CPAS extremely promising for practical applications.

Crosstalk among Oxidative Stress,Autophagy,and Apoptosis in the Protective Effects of Ginsenoside Rb1 on Brain Microvascular Endothelial Cells:A Mixed Computational and Experimental Study

Objective Brain microvascular endothelial cells (BMECs) were found to shift from their usually inactive state to an active state in ischemic stroke (IS) and cause neuronal damage. Ginsenoside Rb1 (GRb1),a component derived from medicinal plants,is known for its pharmacological benefits in IS,but its protective effects on BMECs have yet to be explored. This study aimed to investigate the potential protective effects of GRb1 on BMECs. Methods An in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model was established to mimic ischemia-reperfusion (I/R) injury. Bulk RNA-sequencing data were analyzed by using the Human Autophagy Database and various bioinformatic tools,including gene set enrichment analysis (GSEA),Gene Ontology (GO) classification and enrichment analysis,Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis,protein-protein interaction network analysis,and molecular docking. Experimental validation was also performed to ensure the reliability of our findings. Results Rb1 had a protective effect on BMECs subjected to OGD/R injury. Specifically,GRb1 was found to modulate the interplay between oxidative stress,apoptosis,and autophagy in BMECs. Key targets such as sequestosome 1 (SQSTM1/p62),autophagy related 5 (ATG5),and hypoxia-inducible factor 1-alpha (HIF-1α) were identified,highlighting their potential roles in mediating the protective effects of GRb1 against IS-induced damage. Conclusion GRbl protects BMECs against OGD/R injury by influencing oxidative stress,apoptosis,and autophagy. The identification of SQSTM1/p62,ATG5,and HIF-1α as promising targets further supports the potential of GRb1 as a therapeutic agent for IS,providing a foundation for future research into its mechanisms and applications in IS treatment.

A dynamic database of solid-state electrolyte(DDSE)picturing all-solid-state batteries

All-solid-state batteries(ASSBs)are a class of safer and higher-energy-density materials compared to conventional devices,from which solid-state electrolytes(SSEs)are their essential components.To date,investigations to search for high ion-conducting solid-state electrolytes have attracted broad concern.However,obtaining SSEs with high ionic conductivity is challenging due to the complex structural information and the less-explored structure-performance relationship.To provide a solution to these challenges,developing a database containing typical SSEs from available experimental reports would be a new avenue to understand the structureperformance relationships and find out new design guidelines for reasonable SSEs.Herein,a dynamic experimental database containing>600 materials was developed in a wide range of temperatures(132.40–1261.60 K),including mono-and divalent cations(e.g.,Li^(+),Na^(+),K^(+),Ag^(+),Ca^(2+),Mg^(2+),and Zn^(2+))and various types of anions(e.g.,halide,hydride,sulfide,and oxide).Data-mining was conducted to explore the relationships among different variates(e.g.,transport ion,composition,activation energy,and conductivity).Overall,we expect that this database can provide essential guidelines for the design and development of high-performance SSEs in ASSB applications.This database is dynamically updated,which can be accessed via our open-source online system.

Fine mapping and characterization of stripe rust resistance gene YrAYH in near-isogenic lines derived from a cross involving wheat landrace Anyuehong

Stripe rust,caused by Puccinia striiformis f.sp.tritici(Pst),is a devastating disease in wheat worldwide.Discovering and characterizing new resistance genes/QTL is crucial for wheat breeding programs.In this study,we fine-mapped and characterized a stripe rust resistance gene,YRAYH,on chromosome arm 5BL in the Chinese wheat landrace Anyuehong(AYH).Evaluations of stripe rust response to prevalent Chinese Pst races in near-isogenic lines derived from a cross of Anyuehong and Taichung 29 showed that YrAYH conferred a high level of resistance at all growth stages.Fine mapping using a large segregating population of 9748 plants,narrowed the YRAYH locus to a 3.7 Mb interval on chromosome arm 5BL that included 61 annotated genes.Transcriptome analysis of two NIL pairs identified 64 upregulated differentially expressed genes(DEGs)in the resistant NILs(NILs-R).Annotations indicated that many of these genes have roles in plant disease resistance pathways.Through a combined approach of fine-mapping and transcriptome sequencing,we identified a serine/threonine-protein kinase SRPK as a candidate gene underlying YrAYH.A unique 25 bp insertion was identified in the NILs-R compared to the NILs-S and previously published wheat genomes.An InDel marker was developed and co-segregated with YrAYH.Agronomic trait evaluation of the NILs suggested that YrAYH not only reduces the impact of stripe rust but was also associated with a gene that increases plant height and spike length.

Bioengineered skin organoids:from development to applications

Signifcant advancements have been made in recent years in the development of highly sophisticated skin organoids.Serving as three-dimensional(3D)models that mimic human skin,these organoids have evolved into complex structures and are increasingly recognized as efective alternatives to traditional culture models and human skin due to their ability to overcome the limitations of two-dimensional(2D)systems and ethical concerns.The inherent plasticity of skin organoids allows for their construction into physiological and pathological models,enabling the study of skin development and dynamic changes.This review provides an overview of the pivotal work in the progression from 3D layered epidermis to cyst-like skin organoids with appendages.Furthermore,it highlights the latest advancements in organoid construction facilitated by state-of-the-art engineering techniques,such as 3D printing and microfuidic devices.The review also summarizes and discusses the diverse applications of skin organoids in developmental biology,disease modelling,regenerative medicine,and personalized medicine,while considering their prospects and limitations.

User Instructions for the Dynamic Database of Solid-State Electrolyte 2.0(DDSE 2.0)

The Dynamic Database of Solid-State Electrolyte(DDSE)is an advanced online platform offering a comprehensive suite of tools for solid-state battery research and development.Its key features include statistical analysis of both experimental and computational solid-state electrolyte(SSE)data,interactive visualization through dynamic charts,user data assessment,and literature analysis powered by a large language model.By facilitating the design and optimization of novel SSEs,DDSE serves as a critical resource for advancing solid-state battery technology.This Technical Report provides detailed tutorials and practical examples to guide users in effectively utilizing the platform.

Genome-wide and candidate gene association studies identify BnPAP17 as conferring the utilization of organic phosphorus in oilseed rape

Phosphorus(P)is essential for living plants,and P deficiency is one of the key factors limiting the yield in rapeseed production worldwide.As the most important organ for plants,root morphology traits(RMTs)play a key role in P absorption.To investigate the genetic variability of RMT under low P availability,we dissected the genetic structure of RMTs by genome-wide association studies(GWAS),linkage mapping and candidate gene association studies(CGAS).A total of 52 suggestive loci were associated with RMTs under P stress conditions in 405 oilseed rape accessions.The purple acid phosphatase gene BnPAP17 was found to control the lateral root number(LRN)and root dry weight(RDW)under low P stress.The expression of BnPAP17 was increased in shoot tissue in P-efficient cultivars compared to root tissue and P-inefficient cultivars in response to low P stress.Moreover,the haplotype of BnPAP17^(Hap3)was detected for the selective breeding of P efficiency in oilseed rape.Over-expression of the BnPAP17^(Hap3)could promote the shoot and root growth with enhanced tolerance to low P stress and organic phosphorus(Po)utilization in oilseed rape.Collectively,these findings increase our understanding of the mechanisms underlying BnPAP17-mediated low P stress tolerance in oilseed rape.

Mitigating Lattice Distortion of High‑Voltage LiCoO_(2)via Core‑Shell Structure Induced by Cationic Heterogeneous Co‑Doping for Lithium‑Ion Batteries

Inactive elemental doping is commonly used to improve the structural stability of high-voltage layered transition-metal oxide cathodes.However,the one-step co-doping strategy usually results in small grain size since the low diffusivity ions such as Ti^(4+)will be concentrated on grain boundaries,which hinders the grain growth.In order to synthesize large single-crystal layered oxide cathodes,considering the different diffusivities of different dopant ions,we propose a simple two-step multi-element co-doping strategy to fabricate core–shell structured LiCoO_(2)(CS-LCO).In the current work,the high-diffusivity Al^(3+)/Mg^(2+)ions occupy the core of single-crystal grain while the low diffusivity Ti^(4+)ions enrich the shell layer.The Ti^(4+)-enriched shell layer(~12 nm)with Co/Ti substitution and stronger Ti–O bond gives rise to less oxygen ligand holes.In-situ XRD demonstrates the constrained contraction of c-axis lattice parameter and mitigated structural distortion.Under a high upper cut-off voltage of 4.6 V,the single-crystal CS-LCO maintains a reversible capacity of 159.8 mAh g^(−1)with a good retention of~89%after 300 cycles,and reaches a high specific capacity of 163.8 mAh g^(−1)at 5C.The proposed strategy can be extended to other pairs of low-(Zr^(4+),Ta^(5+),and W6+,etc.)and high-diffusivity cations(Zn^(2+),Ni^(2+),and Fe^(3+),etc.)for rational design of advanced layered oxide core–shell structured cathodes for lithium-ion batteries.

Real-time Abnormal Detection of GWAC Light Curve based on Wavelet Transform Combined with GRU-Attention

Nowadays, astronomy has entered the era of Time-Domain Astronomy, and the study of the time-varying light curves of various types of objects is of great significance in revealing the physical properties and evolutionary history of celestial bodies. The Ground-based Wide Angle Cameras telescope, on which this paper is based, has observed more than 10 million light curves, and the detection of anomalies in the light curves can be used to rapidly detect transient rare phenomena such as microgravity lensing events from the massive data. However, the traditional statistically based anomaly detection methods cannot realize the fast processing of massive data. In this paper, we propose a Discrete Wavelet(DW)-Gate Recurrent Unit-Attention(GRU-Attention) light curve warning model. Wavelet transform has good effect on data noise reduction processing and feature extraction, which can provide richer and more stable input features for a neural network, and the neural network can provide more flexible and powerful output model for wavelet transform. Comparison experiments show an average improvement of 61% compared to the previous pure long-short-term memory unit(LSTM) model, and an average improvement of 53.5% compared to the previous GRU model. The efficiency and accuracy of anomaly detection in previous paper work are not good enough, the method proposed in this paper possesses higher efficiency and accuracy,which incorporates the Attention mechanism to find out the key parts of the light curve that determine the anomalies. These parts are assigned higher weights, and in the actual anomaly detection, the star is detected with83.35% anomalies on average, and the DW-GRU-Attention model is compared with the DW-LSTM model, and the detection result f1 is improved by 5.75% on average, while having less training time, thus providing valuable information and guidance for astronomical observation and research.

In Situ-Constructed Li_(x)MoS_(2)with Highly Exposed Interface Boosting High-Loading and Long-Life Cathode for All-Solid-State Li-S Batteries

As the persistent concerns regarding sluggish reaction kinetics and insufficient conductivities of sulfur cathodes in all-solid-state Li-S batteries(ASSLSBs),numerous carbon additives and solid-state electrolytes(SSEs)have been incorporated into the cathode to facilitate ion/electron pathways around sulfur.However,this has resulted in a reduced capacity and decomposition of SSEs.Therefore,it is worth exploring neotype sulfur hosts with electronic/ionic conductivity in the cathode.Herein,we present a hybrid cathode composed of few-layered S/MoS_(2)/C nanosheets(<5 layers)that exhibits high-loading and long-life performance without the need of additional carbon additives in advanced ASSLSBs.The multifunctional MoS_(2)/C host exposes the abundant surface for intimate contacting sites,in situ-formed LixMoS_(2)during discharging as mixed ion/electron conductive network improves the S/Li2S conversion,and contributes extra capacity for the part of active materials.With a high active material content(S+MoS_(2)/C)of 60 wt%in the S/MoS_(2)/C/Li_(6)PS_(5)Cl cathode composite(the carbon content is only~3.97 wt%),the S/MoS_(2)/C electrode delivers excellent electrochemical performance,with a high reversible discharge capacity of 980.3 mAh g^(-1)(588.2 mAh g^(-1)based on the whole cathode weight)after 100 cycles at 100 mA g^(-1).The stable cycling performance is observed over 3500 cycles with a Coulombic efficiency of 98.5%at 600 mA g^(-1),while a high areal capacity of 10.4 mAh cm^(-2)is achieved with active material loading of 12.8 mg cm^(-2).

Data-Driven Viewpoint for Developing Next-Generation Mg-Ion Solid-State Electrolytes

Magnesium(Mg)is a promising alternative to lithium(Li)as an anode material in solid-state batteries due to its abundance and high theoretical volumetric capacity.However,the sluggish Mg-ion conduction in the lattice of solidstate electrolytes(SSEs)is one of the key challenges that hamper the development of Mg-ion solid-state batteries.Though various Mg-ion SSEs have been reported in recent years,key insights are hard to be derived from a single literature report.Besides,the structure-performance relationships of Mg-ion SSEs need to be further unraveled to provide a more precise design guideline for SSEs.In this viewpoint article,we analyze the structural characteristics of the Mg-based SSEs with high ionic conductivity reported in the last four decades based upon data mining-we provide big-data-derived insights into the challenges and opportunities in developing next-generation Mg-ion SSEs.

Comprehensive analysis and selection of high oleic peanut varieties in China:A study on agronomic,yield,and quality traits

Peanut(Arachis hypogaea L.)is an important oil crop.Oleic acid is a major factor that determines the quality of peanuts.Therefore,the high oleic and high oleic to linoleic acid ratio are the target traits in an advanced peanut breeding program.This study provided an extensive evaluation of the genetic and physical characteristics as well as disease resistance of 220 high oleic peanut varieties in China.Notably,these varieties clustered into five major categories based on their traits.A majority of these varieties have been bred using interspecific hybridization or selected from mutants of self-crossed parents,with the main parent varieties being Kaixuan 016 and CTWE.Analysis of disease resistance showed that most high oleic peanut varieties could resist two or three diseases.However,those varieties with resistance to multiple diseases were relatively scarce.Moreover,some high oleic peanut varieties showed no disease resistance or inadequate testing.The results further indicate that the genetic basis for high oleic peanut breeding is insufficient,highlighting the need for its further development.Importantly,our findings lay a critical foundation for future high oleic peanut breeding and promote better understanding of the genetic and trait diversity offered by these varieties.

Preliminary study on the preparation of lyophilized acellular nerve scaffold complexes from rabbit sciatic nerves with human umbilical cord mesenchymal stem cells

BACKGROUND The gold standard of care for patients with severe peripheral nerve injury is autologous nerve grafting;however,autologous nerve grafts are usually limited for patients because of the limited number of autologous nerve sources and the loss of neurosensory sensation in the donor area,whereas allogeneic or xenografts are even more limited by immune rejection.Tissue-engineered peripheral nerve scaffolds,with the morphology and structure of natural nerves and complex biological signals,hold the most promise as ideal peripheral nerve“replacements”.AIM To prepare allogenic peripheral nerve scaffolds using a low-toxicity decellularization method,and use human umbilical cord mesenchymal stem cells(hUCMSCs)as seed cells to cultivate scaffold-cell complexes for the repair of injured peripheral nerves.METHODS After obtaining sciatic nerves from New Zealand rabbits,an optimal acellular scaffold preparation scheme was established by mechanical separation,varying lyophilization cycles,and trypsin and DNase digestion at different times.The scaffolds were evaluated by hematoxylin and eosin(HE)and luxol fast blue(LFB)staining.The maximum load,durability,and elastic modulus of the acellular scaffolds were assessed using a universal material testing machine.The acellular scaffolds were implanted into the dorsal erector spinae muscle of SD rats and the scaffold degradation and systemic inflammatory reactions were observed at 3 days,1 week,3 weeks,and 6 weeks following surgery to determine the histocompatibility between xenografts.The effect of acellular scaffold extracts on fibroblast proliferation was assessed using an MTT assay to measure the cytotoxicity of the scaffold residual reagents.In addition,the umbilical cord from cesarean section fetuses was collected,and the Wharton’s jelly(WJ)was separated into culture cells and confirm the osteogenic and adipogenic differentiation of mesenchymal stem cells(MSCs)and hUC-MSCs.The cultured cells were induced to differentiate into Schwann cells by the antioxidant-growth factor induction method,and the differentiated cells and the myelinogenic properties were identified.RESULTS The experiments effectively decellularized the sciatic nerve of the New Zealand rabbits.After comparing the completed acellular scaffolds among the groups,the optimal decellularization preparation steps were established as follows:Mechanical separation of the epineurium,two cycles of lyophilization-rewarming,trypsin digestion for 5 hours,and DNase digestion for 10 hours.After HE staining,no residual nuclear components were evident on the scaffold,whereas the extracellular matrix remained intact.LFB staining showed a significant decrease in myelin sheath composition of the scaffold compared with that before preparation.Biomechanical testing revealed that the maximum tensile strength,elastic modulus,and durability of the acellular scaffold were reduced compared with normal peripheral nerves.Based on the histocompatibility test,the immune response of the recipient SD rats to the scaffold New Zealand rabbits began to decline3 weeks following surgery,and there was no significant rejection after 6 weeks.The MTT assay revealed that the acellular reagent extract had no obvious effects on cell proliferation.The cells were successfully isolated,cultured,and passaged from human umbilical cord WJ by MSC medium,and their ability to differentiate into Schwann-like cells was demonstrated by morphological and immunohistochemical identification.The differentiated cells could also myelinate in vitro.CONCLUSION The acellular peripheral nerve scaffold with complete cell removal and intact matrix may be prepared by combining lyophilization and enzyme digestion.The resulting scaffold exhibited good histocompatibility and low cytotoxicity.In addition,hUC-MSCs have the potential to differentiate into Schwann-like cells with myelinogenic ability following in vitro induction.

Unraveling the coordination behavior and transformation mechanism of Cr^(3+) in Fe–Cr redox flow battery electrolytes

Currently,the iron chromium redox flow battery(ICRFB)has become a research hotspot in the energy storage field owing to its low cost and easily-scaled-up.However,the activity of electrolyte is still ambiguous due to its complicated solution environment.Herein,we performed a pioneering investigation on the coordination behavior and transformation mechanism of Cr^(3+)in electrolyte and prediction of impurity ions impact through quantum chemistry computations.Based on the structure and symmetry of electrostatic potential distribution,the activity of different Cr^(3+)complex ions is confirmed as[Cr(H2O)5Cl]^(2+)>[Cr(H2O)4Cl2]+>[Cr(H2O)6]^(3+).The transformation mechanism between[Cr(H2O)6]^(3+)and[Cr(H2O)5Cl]^(2+)is revealed.We find the metal impurity ions(especially Mg^(2+))can exacerbate the electrolyte deactivation by reducing the transformation energy barrier from[Cr(H2O)5Cl]^(2+)(24.38 kcal mol^(−1))to[Cr(H2O)6]^(3+)(16.23 kcal mol^(−1)).The solvent radial distribution and mean square displacement in different solvent environments are discussed and we conclude that the coordination configuration limits the diffusivity of Cr^(3+).This work provides new insights into the activity of electrolyte,laying a fundamental sense for the electrolyte in ICRFB.

Powerlink协议异步调度机制的建模与分析

针对通信协议进行形式化建模与分析,能够很大程度上提高工控协议的安全性。通过分析开源实时以太网Powerlink的同步、异步阶段的不同通信行为,以及在同步阶段的不同通信模式,提出一种利用CSP(Communication Sequential Process)语言对Powerlink协议进行形式化建模的方法。使用该方法能够描述Powerlink在数据链路层上不同节点之间的通信行为,以及描述在随机产生异步请求的情况下,异步阶段的异步请求调度行为。同时,该方法也准确模拟了协议运行过程中,错误处理机制对丢失帧情况的处理过程。最后利用软件PAT(Process Analysis Toolkit)验证了这些异步调度过程是否满足优先级顺序等性质,有助于对协议的运行机制进行深入分析。

Attenuated LKB1-SIK1 signaling promotes epithelial-mesenchymal transition and radioresistance of non–small cell lung cancer cells

Background: Radiotherapy is one of the main therapeutic approaches for non–small cell lung cancer(NSCLC). However, radioresistant cancer cells can eventually cause tumor relapse and even fatal metastasis. It is thought that radioresistance and metastasis could be potentially linked by epithelial?mesenchymal transition(EMT). In this study, we established radioresistant NSCLC cells to investigate the potential relationship among radioresistance, EMT, and enhanced metastatic potential and the underlying mechanism involving liver kinase B1(LKB1)?Salt?inducible kinase 1(SIK1) signaling.Methods: The radioresistant cell lines A549 R and H1299 R were generated by dose?gradient irradiation of the paren?tal A549 and H1299 cells. The radioresistance/sensitivity was evaluated by Cell Counting Kit?8 assay, apoptosis analysis, and/or clonogenic cell survival assay. The EMT phenotype and the signaling change were assessed by Western blot?ting. The abilities of invasion and migration were evaluated by transwell assays and wound healing assays.Results: The radioresistant cell lines A549 R and H1299 R displayed mesenchymal features with enhanced invasion and migration. Mechanistically, A549 R and H1299 R cells had attenuated LKB1?SIK1 signaling, which leaded to the up?regulation of Zinc?finger E?box?binding homeobox factor 1(ZEB1)—a transcription factor that drives EMT. Re?expression of LKB1 in A549 R cells reversed the EMT phenotype, whereas knockdown of LKB1 in H1299 R cells further promoted the EMT phenotype. Moreover, re?expression of LKB1 in A549 cells increased the radiosensitivity, whereas knockdown of LKB1 in H1299 cells decreased the radiosensitivity.Conclusions: Our findings suggest that attenuated LKB1?SIK1 signaling promotes EMT and radioresistance of NSCLC cells, which subsequently contributes to the enhanced metastatic potential. Targeting the LKB1?SIK1?ZEB1 pathway to suppress EMT might provide therapeutic benefits.

Proanthocyanidin B2 attenuates high-glucose-induced neurotoxicity of dorsal root ganglion neurons through the PI3K/Akt signaling pathway

High glucose affects primary afferent neurons in dorsal root ganglia by inhibiting neurite elongation,causing oxidative stress,and inducing neuronal apoptosis and mitochondrial dysfunction,which finally result in neuronal damage.Proanthocyanidin,a potent antioxidant,has been shown to have neuroprotective effects.Proanthocyanidin B2 is a common dimer of oligomeric proanthocyanidins.To date,no studies have reported the neuroprotective effects of proanthocyanidin B2 against high-glucose-related neurotoxicity in dorsal root ganglion neurons.In this study,10 μg/m L proanthocyanidin B2 was used to investigate its effect on 45 m M high-glucose-cultured dorsal root ganglion neurons.We observed that challenge with high levels of glucose increased neuronal reactive oxygen species and promoted apoptosis,decreased cell viability,inhibited outgrowth of neurites,and decreased growth-associated protein 43 protein and m RNA levels.Proanthocyanidin B2 administration reversed the neurotoxic effects caused by glucose challenge.Blockage of the phosphatidylinositol 3 kinase/Akt signaling pathway with 10 μM LY294002 eliminated the protective effects of proanthocyanidin B2.Therefore,proanthocyanidin B2 might be a potential novel agent for the treatment of peripheral diabetic neuropathy.

Nerve Growth Factor and Vascular Endothelial Growth Factor: Retrospective Analysis of 63 Patients with Salivary Adenoid Cystic Carcinoma

Aim To detect the expression of nerve growth factor （NGF） and vascular endothelial growth factor （VEGF） in salivary adenoid cystic carcinoma （SACC） tissues, as well as to determine the correlation between growth factor expression and prognosis in SACC. Methodology Medical records of 63 patients surgically treated for SACC between January 1988 and October 2005 were reviewed. Immunohistochemistry was performed to examine the expression of NGF and VEGF in tumor tissues. Kaplan-Meier analysis and Cox＇s proportional hazard regression model were applied to assess predictors of survival. Results NGF and VEGF were overexpressed in SACC tissues, compared with those in normal salivary tissues （P〈0.05）, and the staining intensity of these two factors was stronger in groups of solid subtype, advanced TNM stage, perineural invasion and recurrence. Patients with high- expression of NGF and VEGF, solid subtype, advanced stage, perineural invasion, recurrence and extended resection alone had worse survival rates （P〈0.05）. Conclusion NGF and VEGF are expressed increasingly in the tissues of SACC cases with invasion and metastasis. NGF expression and VEGF expression are independent prognosis factors for survival.