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The synthesis of two-dimensional molybdenum disulfide (MoS2) has invoked much research interest in recent years. In this work, chemical vapor deposition (CVD) was employed to grow a novel molybdenum disulfide. The synthesis reaction was operated in an inert gas environment, with the sulfur precursor placed in the upstream zone of a double zone tube furnace, and the molybdenum trioxide (MoO3) precursor placed in a small tube in the downstream zone. A piece of glass was used as the substrate, which was placed beside the small tube. We intentionally built a high concentration of molybdenum precursor above the substrate. The specific morphology hinged highly on the concentration of molybdenum. Abundant molybdenum atoms adsorbed on the edges of the bottom MoS2 and formed defects, which promoted the nucleation of the top layer MoS2 and preferentially grew from the edges. This result provides an innovative method to controllably synthesize novel bilayer molybdenum disulfide by a one-step method of chemical vapor deposition.

Protein α-N-methylation is an evolutionarily conserved type of post-translational modification; however, little is known about the regulatory mechanisms for this modification. Methylation at the N6 position of adenosine in mRNAs is dynamic and modulates their stability, splicing, and translational efficiency. Here, we found that the expression of N-terminal methyltransferase 1 (NTMT1) protein is altered by depletion of those genes encoding the reader/writer/eraser proteins of N6-methyladenosine (m6A). We also observed that MRG15 is N-terminally methylated by NTMT1, and this methylation could also be modulated by reader/writer/eraser proteins of m6A. Together, these results revealed a novel m6A-based epitranscriptomic mechanism in regulating protein N-terminal methylation.

An efficient and convenient synthesis of pyrrole-fused tetracyclic skeletons is presented. In this protocol using CuI as a catalyst, 1,1′-biphenyl substrates with 2-alkynoyl and 2′-iodo groups react with isocyanoacetates to provide 7-membered cyclic ketones fused with pyrrole and biphenyl rings through tandem [3 + 2] cycloaddition and C–C coupling processes.

For the industrial implementation of electrochemical hydrogen production, the large-scale production of low-cost, high-efficiency, and stable electrocatalysts that work well at high current densities is critical under alkaline conditions. Here, we report a large-scale approach for the production of low-cost and highly efficient molybdenum selenide–nitride (MoSe2–Mo2N) Schottky heterojunction catalysts. Density functional theory (DFT) shows that the construction of the Schottky heterojunction can induce self-driven electron transfer that not only optimizes the electronic structure at heterointerfaces but also tunes the hydrogen adsorption and dissociation behavior. The MoSe2–Mo2N/Mo electrode delivers a high current density of 1000 mA cm−2 at an overpotential of 462 mV for hydrogen evolution in alkaline media, which are superior to those of commercial Pt/C electrodes. The mature manufacturing technology is scalable and has been confirmed as a feasible strategy to access the large-scale synthesis of molybdenum dichalcogenide-based Schottky heterojunction catalysts at industrial levels.

Fabricating robust and flat photoactive materials is essential for high-performance PEC water splitting and other photovoltaic systems. Herein, we demonstrate a new method for the fabrication of flat and bulky BiVO4 (BVO) crystallites on an FTO substrate. This highly reproducible method can prepare highly active and bulky crystalline BVO (diameter ≤ 4 μm) with abundant oxygen vacancies for PEC water splitting. Moreover, the crystal size and oxygen vacancies of BVO can be controlled by adjusting the pH value of the electrodeposition electrolyte of the Bi precursor. For PEC performance, the FTO/BVO-3 photoanode shows the highest photocurrent (∼1.25 mA cm−2) among the samples in water splitting and 1.75 mA cm−2 with the aid of the impregnated Fe–Pi co-catalyst at 1.23 V vs. RHE under AM 1.5 G illumination. The new findings provide a simple yet efficient method to fabricate bulky and high-performance semi-transparent BVO photoanodes for BVO-based multi-layered tandem solar cell devices for commercial applications.

Undifferentiation is a key feature of nasopharyngeal carcinoma (NPC), which presents as a unique opportunity for intervention by differentiation therapy. In this study, we found that SOX1 inhibited proliferation, promoted differentiation, and induced senescence of NPC cells, which depended on its transcriptional function. RNA-Seq-profiling analysis showed that multiple undifferentiated markers of keratin family, including KRT5, KRT13, and KRT19, were reduced in SOX1 overexpressed NPC cells. Interestingly, gene ontology (GO) analysis revealed genes in SOX1 overexpressed cells were enriched in extracellular functions. The data of LC/MS untargeted metabolomics showed that the content of retinoids in SOX1 overexpressed cells and culture medium was both higher than that in the control group. Subsequently, we screened mRNA level of genes in retinoic acid (RA) signaling or metabolic pathway and found that the expression of UDP-glucuronosyltransferases was significantly decreased. Furtherly, UGT2B7 could rescue the differentiation induced by SOX1 overexpression. Inhibition of UGTs by demethylzeylasteral (T-96) could mimic SOX1 to promote the differentiation of NPC cells. Thus, we described a mechanism by which SOX1 regulated the differentiation of NPC cells by activating retinoid metabolic pathway, providing a potential target for differentiation therapy of NPC.

Molybdenum carbide (Mo2C), a member of transition metal carbides (TMCs), has shown promise in water splitting. Although excellent hydrogen evolution reaction (HER) performance of Mo2C has been achieved both in acid and basic media, the intrinsic hydrogen evolution ability of two-dimensional (2D) Mo2C is still not clear due to the difficulty of calculating the actual active surface area involved in the HER. In this work, the HER activity of Mo2C nanosheets is measured on single 2D Mo2C, which is synthesized through low-temperature carbonization of 2D molybdenum dioxide (MoO2) nanosheets on a SiO2/Si substrate. The edge sites of Mo2C exhibit high catalytic activity with a small Tafel slope of 40.2 mV dec−1 and an overpotential of 152 mV for 10 mA cm−2 in alkaline media. Theoretical analyses reveal that the energy barriers for cleaving the OH–H bond in H2O on the edge of Mo2C are much smaller than those on the basal plane of Mo2C and the Mo site of the edge of Mo2C displays the optimal ΔGH for the H absorption.

Organic–inorganic hybrid perovskite nanowires with well-defined structures have attracted considerable attention for optoelectronic applications. Perovskite nanowires integrated into practical optoelectronic devices are often hindered by the poor crystalline quality. Herein, a ligand-assisted reprecipitation (LARP) strategy is employed to prepare ultralong and freestanding CH3NH3PbI3 nanowires on a large-scale. Oleylamine is adopted as an inhibitor, which can create a passivation layer on the surface of CH3NH3PbI3, to slow down the crystallization rate of CH3NH3PbI3 nanowires. With the low crystallization rate, several millimeters long and high-quality CH3NH3PbI3 nanowires with smooth surfaces can be synthesized on a large scale. Photodetectors fabricated on oleylamine assisted synthesized CH3NH3PbI3 nanowires exhibit high detectivity, which is five times higher than that of non-oleylamine assisted synthesized CH3NH3PbI3 nanowire photoanodes.

Transition metal dichalcogenides (TMDs), such as molybdenum diselenide (MoSe2), have poor alkaline hydrogen evolution activities due to their unfavorable hydrogen adsorption and dissociation properties. In this work, we report a Mo2C/MoSe2 hybrid catalyst seamlessly grown on Mo foil. The Mo2C/MoSe2/Mo electrode exhibits outstanding activity for the hydrogen evolution reaction (HER) with a low overpotential of 51 mV at 10 mA cm−2 in 1 M KOH, significantly outperforming the performances of its MoSe2 and Mo2C counterparts and most reported TMD electrocatalysts in alkaline solution. Moreover, the Mo2C/MoSe2/Mo electrode also possesses good catalytic HER performance in acid. Density functional theory (DFT) calculations reveal that metal-induced gap states formed in the interface region of Mo2C and MoSe2 can make the interfacial semiconducting MoSe2 transform into metallic MoSe2. The transformation is beneficial to speeding up charge transfer between the interfaces, promoting H atom adsorption and desorption kinetics, and therefore enhancing the catalytic performance.

Herein, we report a facile solid-state synthesis strategy for the synthesis of a three-dimensional (3D) macroporous framework molybdenum disulfide-carbide (MoS2-Mo2C) heterojunction. The MoS2-Mo2C/Mo electrode exhibits excellent HER activity with low overpotentials of 56 and 446 mV at current densities of 10 and 1000 mA cm-2, respectively, in alkaline electrolytes.

Background and aims We previously demonstrated that cancer-associated fibroblasts (CAFs) promote tumor growth via recruiting of myeloid-derived suppressor cells (MDSCs). 5-lipoxygenase (5-LO) is highly expressed in myeloid cells and critical for synthesizing leukotriene B4 (LTB4), which is involved in tumor progression via acting its receptor Leukotriene B4 receptor type 2 (BLT2). In this study, we investigated whether and how CAFs regulate MDSC function to enhance cancer stemness, the driving force of the cancer aggressiveness and chemotherapy refractoriness, in highly desmoplastic intrahepatic cholangiocarcinoma (ICC). Approach and results RNA-sequencing analysis revealed enriched metabolic pathways but decreased inflammatory pathways in cancer MDSCs compared with blood MDSCs from ICC patients. Co-injection of ICC patient-derived CAFs promoted cancer stemness in an orthotopic ICC model, which was blunted by MDSC depletion. Conditioned media (CM) from CAF-educated MDSCs drastically promoted tumorsphere formation efficiency and stemness marker gene expression in ICC cells. CAF-CM stimulation increased expression and activity of 5-LO in MDSCs while 5-LO inhibitor impaired the stemness-enhancing capacity of MDSCs in vitro and in vivo. Furthermore, IL-6 and IL-33 mainly expressed by CAFs mediated hyperactivated 5-LO metabolism in MDSCs. We identify the LTB4-BLT2 axis as the critical downstream metabolite signaling of 5-LO in promoting cancer stemness, as treatment with LTB4 that were elevated in CAF-educated MDSCs or blockade of BLT2 that was preferentially expressed in stem-like ICC cells significantly reduced stemness-enhancing effects of CAF-educated MDSCs. Finally, BLT2 blockade augmented chemotherapeutic efficacy in ICC patient derived-xenograft (PDX) models. Conclusions Our study reveals a previously unrecognized role for CAFs in orchestrating the optimal cancer stemness-enhancing microenvironment by educating MDSCs and suggests 5-LO/LTB4-BLT2 axis as promising therapeutic targets for ICC chemoresistance by targeting cancer stemness.

In this work, we report a simple bottom-up approach to synthesize seamless tungsten disulfide (WS2)-tungsten (W) heterojunction electrode for efficient hydrogen evolution reaction (HER). Through one step sulfidation of WO3/W, ultra-thin vertically-arranged WS2 flakes with high surface areas and stepped-structure as well as abundant defects can grow on the W substrate. The synthesized WS2/W electrode exhibits outstanding HER activity with an onset overpotential of as small as approximately 30 mV, and an operating potential of only 108 mV for 10 mA/cm2, which is close to the state-of-the-art transition metal dichalcogenides (TMDs) HER electrocatalyst reported in the literature so far. The abundant exposed edges and defects of WS2 along with excellent electrical contact between WS2 and W substrate contribute to the high HER activity of WS2/W electrode reported in this work.

BACKGROUND This study assessed the effects and underlying molecular mechanisms of ß-asarone on ischemic stroke model rats. MATERIAL AND METHODS Ischemic stroke was induced by middle cerebral artery occlusion (MCAO) in rats. Before and after modeling, cognitive function was evaluated via fear conditioning test and neurological deficit was determined via Longa and Bederson scores. Following treatment with ß-asarone or nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor for 20 consecutive days, the cerebral infarction was detected via TTC staining and Cresyl Violet staining in brain tissues. TUNEL staining and western blot analysis for apoptosis-related proteins were performed to assess the apoptosis of neurons. Nrf2-antioxidant response elements (ARE) pathway-related proteins were examined by RT-qPCR or western blot. RESULTS The cognitive and neurological function was defective in MCAO rats. The infarction volumes and the apoptosis of cortical neurons were significantly increased in brain tissues of model rats, which were ameliorated after treatment with ß-asarone. Meanwhile, the increase in pro-apoptotic proteins and decrease in anti-apoptotic proteins were found in brain tissues of model rats, which were markedly ameliorated by ß-asarone treatment. However, Nrf2 inhibitor worsened the cerebral infarction and the apoptosis of neurons. Western blot results showed that ß-asarone treatment activated the Nrf2-ARE pathway-related proteins in model rats, which was inhibited by Nrf2 inhibitor. CONCLUSIONS Our findings suggest that ß-asarone treatment ameliorated the cerebral infarction in MCAO rats, which could be related to activation of the Nrf2-ARE pathway.

Purpose: The aim of this study was to assess the effect of phillygenin (PHI) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and understand its underlying mechanisms. Methods: Mice were separated into four different groups at random, including LPS, LPS+ PHI (5 mg/kg), LPS + PHI (50 mg/kg) and control group. The two LPS + PHI groups were intraperitoneally administered with PHI after LPS intratracheal administered for 1 h. Subsequently, the lung tissues of different groups were collected and evaluated by H&E staining and W/D (W/D) ratio. The inflammatory cytokines in BALF or lung tissue were also assessed. Western blot assay was applied to examine the expressions of TLR4, MyD88, and NF-κB. Results: The ameliorated pathological changes and lung W/D ratio demonstrated that PHI dramatically suppressed the lung injury levels. PHI strikingly reduced the number of inflammatory cell counts and total protein concentration in BALF. In addition, PHI attenuated expression of IL-1β and TNF-α in BALF and lung tissue. Furthermore, it was confirmed that PHI alleviated LPS-induced ALI via TLR4/MyD88/NF-κB pathway. Conclusions: Together the above results show that PHI attenuates LPS-induced ALI via inactivation of TLR4/MyD88/NF-κB pathway in newborn mice.

Background Interleukin-6 (IL-6) was proposed to be associated with the severity of coronavirus disease 2019 (COVID-19). The present study aimed to explore the kinetics of IL-6 levels, validate this association in COVID-19 patients, and report preliminary data on the efficacy of IL-6 receptor blockade. Methods We conducted a retrospective single-institutional study of 901 consecutive confirmed cases. Serum IL-6 concentrations were tested on admission and/or during hospital stay. Tocilizumab was given to 16 patients with elevated IL-6 concentration. Results 366 patients were defined as common cases, 411 patients as severe, and 124 patients as critical according to the Chinese guideline on diagnosis and treatment of COVID-19. The median concentration of IL-6 was P P P = 0.12). Conclusion Serum IL-6 should be included in diagnostic work-up to stratify disease severity, but the benefit of tocilizumab needs further confirmation. Trial registration retrospectively registered.

Leukotriene B4 (LTB4) is a major type of lipid mediator that is rapidly generated from arachidonic acid through sequential action of 5-lipoxygenase (5-LO), 5-lipoxygenase-activating protein (FLAP) and LTA4 hydrolase (LTA4H) in response to various stimuli. LTB4 is well known to be a chemoattractant for leukocytes, particularly neutrophils, via interaction with its high-affinity receptor BLT1. Extensive attention has been paid to the role of the LTB4-BLT1 axis in acute and chronic inflammatory diseases, such as infectious diseases, allergy, autoimmune diseases, and metabolic disease via mediating recruitment and/or activation of different types of inflammatory cells depending on different stages or the nature of inflammatory response. Recent studies also demonstrated that LTB4 acts on non-immune cells via BLT1 to initiate and/or amplify pathological inflammation in various tissues. In addition, emerging evidence reveals a complex role of the LTB4-BLT1 axis in cancer, either tumor-inhibitory or tumor-promoting, depending on the different target cells. In this review, we summarize both established understanding and the most recent progress in our knowledge about the LTB4-BLT1 axis in host defense, inflammatory diseases and cancer.

Free thiols, or unpaired cysteines, are important product quality attributes in the therapeutic proteins due to their potential impact on the protein structure, bioactivity and stability. While many free thiol quantitation methods were developed for specific therapeutic formats, an unmet need still exists for a multiproduct, high-throughput method for free thiol quantitation. In this study, a workflow was established that combines N-cyclohexylmaleimide (NcHM) derivatization and high-throughput reversed-phase ultra-high performance liquid chromatography (RP-UHPLC) separation with superficially porous particle (SPP) column for quantitating total free thiols in monoclonal antibodies (mAbs), fragment antigen-binding (Fab), and bispecific antibodies (BsAbs). The NcHM derivatization increases the hydrophobicity of the free thiol variants and allows the further separation and quantitation with RP-UHPLC. A thorough evaluation of sample preparation, column selection, chromatographic condition and LC-MS peak identification was performed to optimize and characterize the method outputs. Method optimization resulted in a 42-minute total analysis time. Method qualification demonstrated suitable accuracy, precision, linearity, specificity and robustness. This high-throughput method is not only used for quantitation of total free thiols for both in-process testing and drug substance/drug product batch testing, but also for provide the positional distribution of the free thiols in the protein.

Bamboo powder and its dissolution process in ionic liquids were analyzed according to Fourier Transform Infrared Spectroscopy (FT-IR) coupled with two-dimensional correlation spectroscopy and chemometrics. Second derivative spectroscopy was applied to enhance the spectra resolution, obtaining more molecular vibration information. After executing the principal component analysis (PCA) on ATR-FTIR spectra of undissolved bamboo powder residue, we obtained a three-staged dissolution process model. In addition, the conclusion that cellulose/hemicellulose dissolving prior to lignin was summarized through the PCA loading spectrum. Point-line moving window two dimensional correlation spectroscopy (PL-MW2DCOS) furtherly unveiled the dissolution details. This work provided us a clear dissolution process of biomass using a rapid, label-free and easy-operation method.

An asymmetric oxidative C-N bond-forming reaction is developed using a chiral diiodospirobiindane derivative as the catalyst and mCPBA as a terminal oxidant. The protocol is based on an asymmetric desymmetrization strategy and affords lactams or spirolactams according to the different substituents on the substrates. The products are obtained in good yields and moderate to high enantioselectivities.

Background Several latest guidelines and consensus statements from Europe and the United States specify that there is no need for fasting prior to routine lipid tests. However, the latest Chinese guidelines still recommend fasting tests owing to a lack of local evidence. This study aimed to investigate postprandial lipid concentrations and daytime biological variation of lipids in a healthy Chinese population. Methods Venous blood samples were collected from 41 ostensibly healthy Chinese volunteers at five time points during the day (06:30, 09:00, 12:00, 15:00, and 18:30). The same batch of reagents was used to determine lipid concentrations. A nested ANOVA was performed to calculate within-subject biological variation (CV(I)) and between-subject biological variation (CV(G)). Results Postprandial concentrations of triglyceride were higher than fasting concentrations, with the maximum change occurring at 12:00 (0.5 hours after lunch, 0.21±0.65 mmol/L difference). The daytime biological variation of triglycerides was relatively high (CV(I)=25%, CV(G)=35.9%). The postprandial concentrations of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A1, and apolipoprotein B were mostly lower than the fasting concentrations, and their daytime biological variations were relatively low (CV(I)=2.4-4.4%, CV(G)=11.8-18.7%). Conclusions As most daytime lipid concentrations changed only slightly, non-fasting samples could be used for routine lipid tests. However, in cases of abnormal postprandial triglyceride concentrations, dietary factors and fasting time should be considered when interpreting the results.

Anemone flaccida Fr. Shmidt (Ranunculaceae), known as 'Di Wu' in China, is a perennial herb which has long been used to treat arthritis. The rhizome of A. flaccida contains pharmacologically active components i.e. oleanane-type triterpenoid saponins. Oleanolic acid is natural triterpenoid in plants with diverse biological activities. The biosynthesis of oleanolic acid involves cyclization of 2,3-oxidosqualene to the oleanane-type triterpenoid skeleton, followed by a series of oxidation reactions catalyzed by cytochrome P450 monooxygenase (CYP450). Previously, we identified four possible cytochrome P450 genes belonging to CYP716A subfamily from the transcriptome of A. flaccida. In this study, we identified one of those genes "CYP716A254" encoding a cytochrome P450 monooxygenase from A. flaccida that catalyzes the conversion of the β-amyrin into oleanolic acid. The heterologous expression of CYP716A254 in yeast resulted in oxidation of β-amyrin at the C-18 position to oleanolic acid production. These results provide an important basis for further studies of oleanane-type triterpenoid saponins synthesis in A. flaccida.

A methylene blue-based near-infrared fluorescent probe was designed for the selective determination of hypochlorite (ClO−), over other reactive oxygen species or interfering agents. Acetylated methylene blue was synthesized by introducing the acetyl group into the methylene blue framework, which can specifically recognize exogenous and endogenous ClO−. The acetylated methylene blue fluorescent probe was characterized by 1H NMR, 13C NMR and HRMS. The response process and possible mechanism were studied using products of the probe. The emission response of the probe to ClO− presented good linear relationship in the 0–60 μM concentration range, with the detection limit of 0.1 μM (measured at 660 nm and 690 nm). The absorption and emission wavelengths of acetylated methylene blue are both in the near-infrared region; in addition, the probe itself and the degradation products were well-dissolved in water and have almost no toxicity. The probe was used for intracellular ClO− imaging and showed a large fluorescence enhancement (about 200-fold increase).

A series of hyperbranched graft copolymers with hyperbranched polyethylenimine (HPEI) as core and hyperbranched polyglycerol (HPG) as shell (HPEI-g-HPG) were used as nanoreactors and stabilizers for the synthesis of CdS quantum dots (QDs). The preparation conditions were optimized to obtain CdS QDs with a stronger fluorescence. Stable CdS QDs could be prepared by using HPEI-g-HPGs or HPEI homopolymer, but not HPG homopolymer. The CdS QDs capped by HPEI-g-HPGs emitted stronger than those capped by HPEI. Moreover, the photoluminescence intensity increased pronouncedly with increasing the HPG shell content of HPEI-g-HPG stabilizer. The measurements of UV–vis spectroscopy, transmission electron microscopy and dynamic light scattering further verified the formation of CdS QDs. Compared with the CdS QDs capped by HPEI, those capped by HPEI-g-HPGs showed a better storing stability in solution at 4 °C. The as-prepared CdS QDs were only stable in the pH range of 7.0–9.0. It was found that increasing the HPG shell content of HPEI-g-HPG stabilizer could effectively raise the selectivity of the as-prepared CdS QDs towards Hg2+. As the ratiometric fluorescence sensors, CdS QDs capped by HPEI-g-HPGs were most sensitive to Hg2+ and the limit of detection was ca. 1.5 × 10−8 M.

A diversified synthesis of 2-(4-oxo[1,2,3]triazolo-[1,5-a]quin­oxalin-5(4H)-yl)acetamide derivatives is demonstrated. The protocol employs a Ugi four-component reaction for the assembling of N-(2-haloaryl)propynamide intermediates and followed by a copper-catalyzed tandem reaction of the synthetic N-(2-haloaryl)propynamides with sodium azide. Such a method provides rapid access to structurally varied and complex fused tricyclic scaffolds through readily available starting materials.

Alzheimer's disease (AD) is characterized by brain deposition of amyloid plaques and tau neurofibrillary tangles along with steady cognitive decline. Synaptic damage, an early pathological event, correlates strongly with cognitive deficits and memory loss. Mitochondria are essential organelles for synaptic function. Neurons utilize specialized mechanisms to drive mitochondrial trafficking to synapses in which mitochondria buffer Ca2+ and serve as local energy sources by supplying ATP to sustain neurotransmitter release. Mitochondrial abnormalities are one of the earliest and prominent features in AD patient brains. Amyloid-β (Aβ) and tau both trigger mitochondrial alterations. Accumulating evidence suggests that mitochondrial perturbation acts as a key factor that is involved in synaptic failure and degeneration in AD. The importance of mitochondria in supporting synaptic function has made them a promising target of new therapeutic strategies for AD. Here, we review the molecular mechanisms regulating mitochondrial function at synapses, highlight recent findings on the disturbance of mitochondrial dynamics and transport in AD, and discuss how these alterations impact synaptic vesicle release and thus contribute to synaptic pathology associated with AD.

Pterocarine and galeon are typical examples of diarylether heptanoids (DAEHs) with planar chirality due to the strictly constrained conformations in their molecular skeletons. The characterized oxa[1,7]metapara-cyclophane motifs in DAEHs impose great challenges for their enantioselective synthesis. The asymmetric syntheses of (−)-pterocarine and (−)-galeon are demonstrated by employing a chiral phase transfer-catalyzed highly enantioselective SNAr cyclization as the key step for the formation of a diarylether cyclophane skeleton.

Diabetes is commonly associated with liver lipid metabolism disorders. AMP-activated protein kinase (AMPK) has a key role in regulating lipid metabolism. Grape seed procyanidin B2 (GSPB2), a natural polyphenol polymer, ameliorates mitochondrial dysfunction and inhibits oxidative stress or apoptosis via AMPK pathways. In the present study, the hypothesis that GSPB2 treatment may ameliorate liver lipid metabolic disorders by activating AMPK and downstream pathways was tested in diabetic mice. Db/m mice were used as controls, and diabetic db/db mice were randomly divided into 2 groups for treatment: Vehicle and GSPB2 (30 mg/kg/day for 10 weeks). Animals were weighed every week. Fasting blood was collected prior to sacrifice to measure fasting blood glucose (FBG), triglycerides (TG) and total cholesterol (TC). Hepatic TG and free fatty acid (FFA) levels were analyzed. Hepatic sections were examined by light microscopy following hematoxylin and eosin staining. The expression of hepatic AMPK, phosphorylated acetyl‑CoA carboxylase (ACC), carnitine palmitoyl transferase 1 (CPT1) and 4‑hydroxynonenal (4‑HNE) was measured by western blot analysis. Liver mitochondria were isolated to assess electron transport complex I (CI), complex II (CII) and complex IV by high-resolution respirometry. The results demonstrated that GSPB2 significantly decreased body weight and serum TG, TC and FFA levels, but not FBG levels in diabetic mice. GSPB2 visibly decreased lipid droplet accumulation in the liver and significantly reduced hepatic TG and FFA levels. In diabetic mice, GSPB2 restored liver AMPK and ACC phosphorylation, increased CPT1 protein expression, ameliorated lipid peroxidation damage, which was assessed by comparing 4‑HNE levels, and partially restored the damaged mitochondrial respiratory capacity of CI and CII in the liver. In conclusion, long‑term oral treatment with GSPB2 may benefit hepatic lipid metabolism disorders, potentially by decreasing hepatic lipid synthesis and increasing hepatic FFA β‑oxidation via the AMPK‑ACC pathway.

An enantioselective desymmetric aryl C-O coupling reaction was demonstrated under the catalysis of CuI and a chiral cyclic diamine ligand. A series of chiral oxygen-containing heterocyclic units such as 2,3-dihydrobenzofurans, chromans, and 1,4-benzodioxanes with tertiary or quaternary stereocarbon centers were synthesized with this method. DFT calculations were also carried out for a better understanding of the model for enantiocontrol.

Silicon (Si) is an attractive semiconductor which has broad applications in photovoltaic fields due to its low cost and narrow band gap (∼1.1 eV). Taking advantage of a Si-based metal–insulator–semiconductor (MIS) device, which has high electron–hole separation efficiency due to the confined electron and hole transport directions, for the first time, a Pt/ZrO2/n-Si photoanode is directly employed as the anode for the ethanol oxidation reaction (EOR). When exposed to visible light irradiation, the Pt/ZrO2/n-Si photoanode exhibits apparently improved EOR activity and durability. This work provides a simple way to fabricate Si-based EOR photoanodes, which has potential for application in direct ethanol fuel cells.

Hyperbranched polyethylenimine (HPEI) was modified with glycidol, resulting in hydroxyl terminated HPEI (HPEI-OH). Subsequently, HPEI-OH was used as the macroinitiator to initiate the anionic ring-opening polymerization of glycidol, realizing the hyperbranched grafting copolymer with HPEI as core and hyperbranched polyglycerol (HPG) as shell (HPEI- g -HPG) through the 'grafting from' method. The diagrams from gel permeation chromatography (GPC) showed that the products were a mixture of copolymers and homopolymers. A two-step purification method was developed to separate HPEI- g -HPGs from the mixture, which was much more effective than the normally-adopted dialysis method. The hyperbranched grafting polymerization condition was optimized and the maximal grafting efficiency was found to be ca. 30%. Under the optimal grafting polymerization condition, we prepared a series of HPEI- g -HPG copolymers that have the same HPEI core, but have a different number of glycidol units in the HPG shell. The detailed structural information of these copolymers was deduced from 1 H NMR, inverse gated decoupled 13 C NMR and GPC measurements. Although no traditional fluorophores existed in HPEI- g -HPGs, HPEI- g -HPGs could emit blue fluorescence centered at ca. 470 nm. The fluorescence intensity was influenced pronouncedly by the thickness of HPG shell, pH, oxidation time, the amount of THF in the solvent mixture. The detailed characterizations and analyses supported that the luminogen of HPEI- g -HPGs was tertiary amine oxide.

A copper-catalyzed intramolecular asymmetric double C-arylation reaction was developed. The method provides a facile approach to chiral spiro bis-oxindoles in high yields and with good to excellent enantioselectivities. It also shows a broad substrate scope and good functional group tolerance. Density functional theory (DFT) calculations were conducted and revealed that the enantioselectivity is determined at the oxidative addition of Cu(I) into the second C–I bond.

The objective of the present study was to explore the effects of environmental chemicals, such as methyl mercury, paraquat, and bisphenol A, on cell proliferation and apoptosis, as well as the expression levels of neuronal differentiation-related genes in neural stem cells (NSCs). NSCs originated from human umbilical cord blood (HUCB-NSCs) were used as cell models in the current study. CCK-8 and flow cytometry experiments were performed to assess the effects of methyl mercury, paraquat, and bisphenol A on the proliferation and apoptosis of HUCB-NSCs at different processes, including proliferation and differentiation stages. The expressions of neuronal differentiation-related genes were determined by reverse transcription-polymerase chain reaction and western blot analysis. The results showed that methyl mercury, paraquat, and bisphenol A treatments significantly inhibited cell proliferation and induced cell apoptosis in HUCB-NSCs, as well as decreased the expressions of Oct4, Gdf3, and Sox1, whereas increased Pax6 and Ngn1 expressions at both mRNA and protein levels. In conclusion, this study demonstrates that environmental chemicals can impair the proliferation and differentiation of NSCs, which may cause abnormal development of the nervous system.

Background: For treating spleen-deficiency syndrome (SDS), atractylodis rhizoma (AR) is usually treated with bran, which is measured to enhance efficacy. Newly, we found that bran-fried AR (BFA) had benefits over raw AR in refining gut flora. However, the change about metabolism of gut flora caused by raw and BFA remains unclear. Aim: The aim of this study was to compare the difference between raw and BFA acting on short-chain fatty acid (SCFA) metabolism in SDS rats, a metabolic pathway comprising gut flora. Materials and Methods: The model of SDS rats was recognized and then given raw and BFA by gavage. The serum was collected for the determination of motilin (MTL), gastrin (GAS), trypsin (TRY), and amylase (AMS) by enzyme-linked immunosorbent assay. The feces were collected for the determination of 7 SCFAs under selective ion monitoring mode by gas chromatography-mass spectrometer. Results: Raw and BFA can upsurge the levels of MTL, GAS, TRY, and AMS in the serum of SDS rats, diminution the levels of acetic acid and propionic acid, and rise the level of hexanoic acid in the feces of SDS rats, and BFA showed noteworthy activity than raw AR. Conclusion: Raw and BFA can improve the acetic acid, propionic acid, and hexanoic acid metabolism in SDS rats, and BFA was more potent than raw AR.

Introduction Macrophages are capable of exerting both proinflammatory and anti-inflammatory functions in response to distinct environmental stimuli, by polarizing into classically inflammatory state (M1) and anti-inflammatory phenotype (M2), respectively. The Wnt/β-catenin signaling plays an important role in the tissue homeostasis and immune regulations, including the macrophage polarizations. However, the molecular mechanism of Wnt/β-catenin signaling in regulating alveolar macrophage polarization in an inflammatory state remains unclear. Methods The Wnt/β-catenin signaling-altered phenotypes of murine macrophage-like RAW264.7 cells in vitro and alveolar macrophage in vivo in both of naïve and lipopolysaccharide-induced inflammation states were accessed by immunoblotting and immunostaining assays. Results The activation of Wnt/β-catenin signaling inhibited macrophage M1 polarization, but promoted alternative M2 polarization in murine RAW264.7 cells under a naïve state. Interestingly, in an LPS-induced inflammation condition, the enhanced Wnt/β-catenin activity suppressed both M1 and M2 polarizations in RAW264.7 cells in vitro, and primary alveolar macrophages of LPS-challenged mice in vivo. Molecular analysis further demonstrated an involvement of Stat signing in regulating Wnt/β-catenin signaling-altered polarizations in mouse alveolar macrophages. Conclusion These results suggest a mechanism by which Wnt/β-catenin signaling modulates macrophage polarization in an inflammation state by regulating the Stat signaling pathway.

Enantioselective C–P cross-coupling of diarylphosphine oxides with ortho-substituted aryl iodides has been achieved via kinetic resolution strategy, affording chiral triarylphosphine oxides in high yields and with moderate to high enantioselectivity.

Sialic acid modification is a kind of post-translational modification. To investigate the regulation effect of sialic acid on neural differentiation, we used CycloManN propanyl perac (CycloManN pro), a metabolic precursor of sialic acid, to treat PC12 cells. We noted that CycloManN pro indeed robustly promoted global sialylation detected by MAL II lectin blot in PC12 cells. Simultaneously, we interestingly found that the neurite outgrowth of PC12 cells was significantly promoted by the CycloManN pro treatment. The profile analysis of sialylated proteins showed that a protein band at 55KD was greatly enhanced especially in PC12L cells after CycloManN pro treatment. After enrichment with lectin MAL II, the proteins in this band were analyzed by mass spectrometry. The results showed that 23 proteins were in the band, but the score of vimentin was the highest among them. To investigate further the role of vimentin in the process of neurite differentiation, vimentin construct was transfected into PC12 cells. We interestingly observed that ectopic expression of vimentin significantly enhanced the neurite outgrowth induced by CycloManN pro. However, after three potential glycosylation sites (Ser-7, Thr-33, Ser-34:) of vimentin were mutated to alanine, overexpression of the mutated vimentin completely lost the enhancement activity for the neural differentiation even in the presence of CycloManN pro. Taken together, our study demonstrated that vimentin was important in the induction of neural differentiation by CycloManN pro.

Cranial irradiation-induced inflammation plays a critical role in the initiation and progression of radiation-induced brain injury (RIBI). Anti-inflammation treatment may provide therapeutic benefits. Corilagin (beta-1-O-galloyl-3, 6-(R)-hexahydroxydiphenoyl-D-glucose, C27H22O18) was a novel member of the tannin family with anti-inflammatory properties and is isolated from some medicinal plants, such as Phyllanthus amarus and Caesalpinia coriaria. In this study, the effect of Corilagin on RIBI was investigated and the underlying mechanisms were explored. Spatial learning and memory ability of mice were investigated by the Morris water maze test. Evans blue leakage and electron microscopy were used to assess the integrity of blood-brain barrier (BBB). The mRNA and protein expressions of inflammatory cytokines, TNF-α and IL-1β, were measured by using real-time PCR and Western blotting. The activation of microglial cells and expression of TNF-α were examined by immunofluorescence staining. Phosphorylated signal transducers and activators of transcription 3 (p-STAT3) and IκBα, and the translocation of p65 from cytoplasm to nucleus were detected by using Western blotting. Morris water maze test showed that Corilagin ameliorated the neurocognitive deficits in RIBI mice. Evans blue leakage and electron microscopy exhibited that Corilagin partially protected the BBB integrity from cranial irradiation-caused damage; immunofluorescence staining showed that Corilagin could inhibit microglial activation and TNF-α expression. Real-time PCR and Western blotting revealed that Corilagin downregulated the expression of TNF-α and IL-1β and inhibited the irradiation-induced activation of NF-κB pathways by upregulating p-STAT3 expression. In conclusion, Corilagin could attenuate RIBI through inhibiting microglial activation and the expressions of inflammatory cytokines. Corilagin might inhibit the activation of NF-κB pathway in a STAT3-associated manner, thereby downregulating the inflammatory cytokine expressions.

Copper-catalyzed (or -mediated) asymmetric coupling reactions have received significant attention over the past few years. Especially the coupling reactions of aryl or alkyl halides with nucleophiles became a very powerful tool for the formation of C–C, C–N, C–O and other carbon–heteroatom bonds as well as for the construction of heteroatom-containing ring systems. This review summarizes the recent progress in copper-catalyzed asymmetric coupling reactions for the formation of C–C and carbon–heteroatom bonds.

Two isomorphic 3D MOFs [Cd(2-bpeb)(sdba)] (1) and [Zn(2-bpeb)(sdba)] derived from the π-conjugated pro-ligand 2-(4-((E)-2-(pyridine-2-yl)vinyl)styryl)pyridine (2-bpeb) and 4,4′-sulfonyldibenzoate (H2sdba) were synthesized and characterized. Complexes 1 and 2 exhibit striking fluorescence properties and can function as chemical sensors via rapid luminescence quenching in the presence of Fe3+and Cr2O72− in aqueous media with high sensitivity and selectivity.

Metal sulfides (MoS2) for hydrogen evolution reaction (HER) catalysts typically suffer from inert kinetics, especially in alkaline conditions, due to its improper hydrogen adsorption/desorption capability on the basal plane S atoms. However, the hydrogen adsorption/desorption can be tuned by modulating the electron state by introducing the dopants in the basal plane of MoS2. Herein, we report a MoO2/MoS2 structure for efficient HER in alkaline and acidic electrolyte. The design of this high-performance MoO2/MoS2|P electrode is verified by density functional theory (DFT) calculation. The calculation demonstrates that the electron state of ultra-thin MoS2 can be modulated by the substitution reaction (S-O or P-O) on MoO2 surface to optimize hydrogen binding behavior and thus promote HER kinetics. Particularly, MoO2/MoS2|P (P doped) electrode exhibits an overpotential of 45 mV for 10 mA/cm2, which is a record low value among the reported transition metal dichalcogenides (TMDs) measured in the alkaline electrolyte so far.

Atractylodis Rhizoma, a classical Chinese medicine, exhibits unambiguous therapeutic effect on spleen deficiency in China for decades. The aim of the present study was to explore the different effects on the composition and level of endogenous metabolites in rats with spleen deficiency after oral administration of raw and bran-fired Atractylodis Rhizoma, and to explain the mechanism of pharmacodynamic enhancement of the bran-fried Atractylodis Rhizoma from the perspective of metabolomics. With this purpose, spleen deficiency model was established by diet, excessive fatigue and bitter cold diarrhea. Then, Enzyme-linked immunosorbent assay (ELISA) was used to determine the contents of vasoactive intestinal peptide (VIP), Somatostatin (SS), substance P (SP) and succinodehydrogenase (SDH) in rats of each group, and to compare the contents of VIP, SS, SP and SDH among groups. UHPLC-Q-TOF-MS based metabolomics was adopted to analyze the plasma from spleen deficiency rats and control rats. Principle component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were utilized to identify differences of metabolic profiles in rats among the control group and the model group；The OPLS-DA were used to analyze the effects of raw and bran-fried Atractylodis Rhizoma on the same metabolites. The results showed that compared with the control group, the contents of VIP, SS, SP and SDH in the plasma of model group decreased, which proved the success of the model group. Compared with model group, the contents of VIP, SS, SP and SDH in the plasma of raw and bran-fried Atractylodis Rhizoma increased, and the effect of bran-fried Atractylodis Rhizoma was better than that of raw Atractylodis Rhizoma. Metabolomics results showed that seventeen different metabolites of spleen deficiency were screened out in the plasma of rats with spleen deficiency compared with the control group. Among them, Nicotinic acid, Dihydrofolic acid, Pantetheine 4'-phosphate and Photophatidylcholine (PC) were the metabolites significantly associated with spleen deficiency, and bran-fried Atractylodis Rhizoma had better intervention and regulation. Through the analysis of metabolic pathways related to these different metabolites of spleen deficiency, and primarily involved in glucosamine metabolism, one carbon pool by folate and so on. This study showed that Atractylodis Rhizoma could provide satisfactory therapeutic effects on spleen deficiency and metabolomics study can be utilized to further understand the molecular mechanisms.

Guanosine monophosphate synthetase (GMPS) is a glutamine amidotransferase catalyzing amination of xanthosine monophosphate (XMP) to form GMP. It is a enzyme involved in de novo purine biosynthesis. T and B lymphocytes, and certain cancer cells, such as malignant melanoma are dependent on de novo synthesis of purine nucleotide for activation and proliferation. GMPS is an attractive target for drug discovery and development to treat autoimmune diseases, organ transplant rejection, and cancers. Mycophenolate acid (MPA), an active ingredient of Mycophenolate Mofetil (Cellcept) has been used for organ transplantation and autoimmune diseases. MPA is a natural product which inhibits inosine monophosphate dehydrogenase (IMPDH), an enzyme upstream of GMPS. Using IMTACTM (Isobaric Mass Tagged Affinity Characterization) platform to perform global proteome ligand screen in live cancer cells, a highly potent and highly selective irreversible inhibitor against GMPS was discovered. Here we report the identification, in vitro characterization and in vivo evaluation of this molecule BGS2019. Target engagement of BGS2019 was determined by In-Gel-Fluorescent assay in cell with an EC50 of 15.6nM. It inhibited GMPS enzymatic activity with an IC50 of 6nM. The mechanism of BGS2019 in cell-based assays was tested, which showed the accumulation of IMP (the substrate for GMPS) and the reduction of GMP, GDP and GTP, upon BGS2019 treatment. BGS2019 was evaluated for its cell growth inhibition activity in several cancer cell lines and it suppressed cancer cell growth with IC50 values from 30nM to 100nM. In vivo administration of BGS2019 was well tolerated in mice and exhibited tumor suppression in animal model. Citation Format: Hang Chen, Heather Ha, Robert Stanley, Cindy Huang, Qian Cai, Irene Yuan, Ping Cao. Discovery of BGS2019, a highly potent and selective covalent inhibitor of GMPS using IMTACTM platform [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr B135. doi:10.1158/1535-7163.TARG-19-B135

Puerarin has long been used as a traditional Chinese medicine, which possesses various physiological properties, including anti-inflammation, anti-oxidative, anti-diabetic and anti-cancer activities. The aim of the current study was to investigate the effect of puerarin on delayed-type hypersensitivity (DTH) induced by ovalbumin (OVA) in mice and explore its underlying mechanisms. The results showed that puerarin significantly attenuated DTH, resulting from a decrement in footpad swelling, reduction in inflammatory cell as well as a decline in anti-OVA IgG in serum. In the homogenized supernatant of footpad tissues, the classic Th1-cytokines, including interferon (IFN)-γ was suppressed following puerarin treatment. Furthermore, a high dose of puerarin inhibited interleukin (IL)-4 production, the classic Th2-cytokine. The concanavalin A stimulation and MTT assays indicated a suppressive effect of puerarin on Th1 response via decreasing IFN-γ production in OVA-primed lymphocytes. Detailed studies revealed that puerarin modulated the Th1/Th2 balance in DTH responses, attributing to lower T-bet/GATA binding protein-3 mRNA and protein level ratios, which led to the shift change of IFN-γ/IL-4 with puerarin treatment. These findings demonstrate that puerarin alleviated inflammation in DTH triggered by OVA application via curbing inflammatory cytokines by modulating the Th1/Th2 balance. These results suggest that puerarin may be an alternative therapeutic option for the treatment of DTH.

1. Geniposide (genipin 1-O-glucose), one of the major bioactive constituents isolated from Fructus Gardeniae, possesses many biological activities. In this study, an efficient strategy was developed using ultra-high-performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometer (UPLC-LTQ-Orbitrap) to profile the in vitro and in vivo metabolic patterns of geniposide in rat liver microsomes (RLMs), plasma, urine, and various tissues. And post-acquisition data-mining methods including extracted ion chromatogram (EIC), multiple mass defect filters (MMDF), fragment ion searching (FISh), and isotope pattern filtering (IPF) were adopted to characterize the known and unknown metabolites. 2. A total of 33 metabolites were detected and interpreted according to accurate mass measurement, diagnostic fragment ions, relevant drug biotransformation knowledge, and bibliography data. Among them, 17 metabolites were detected in the plasma, 31 metabolites were identified in the urine, six metabolites could be found in rat heart, 12 in liver, three in spleen, six in lung, 12 in kidney, six in brain, and four in RLMs. 3. A series of corresponding reactions such as hydrolysis, hydroxylation, taurine conjugation, hydrogenation, decarboxylation, demethylation, sulfate conjugation, cysteine S-conjugation, glucosylation, and their composite reactions were all discovered. 4. The results could provide comprehensive insights and guidance for elucidation of side effect mechanism and safety monitoring as well as for rational formulation design in drug delivery system. The newly discovered geniposide metabolites could be targets for future metabolism studies on the important chemical constituents from herbal medicines.

O-Heterocyclic structures such as 2,3-dihydrobenzofurans are key motifs in many natural compounds and pharmaceuticals. Enantioselective formation of chiral dihydrobenzofurans and analogues was achieved through a copper-catalyzed desymmetrization strategy with a chiral cyclic 1,2-diamine. A broad range of substrates are compatible with this Cu(I)-diamine catalytic system and afford the desired coupling products with chiral tertiary or quaternary carbon centers in high yields and good to excellent enantioselectivities under mild conditions.

During a screening program for new agrochemicals from Chinese medicinal herbs and local wild plants, the petroleum ether (PE) extract of Atractylodes lancea (Thunb.) rhizomes was found to possess repellent and contact activities against Tribolium castaneum adults. Bioactivity-directed chromatographic separation of PE extract on repeated silica-gel columns led to the isolation of two polyacetylenes, atractylodin and atractylodinol (1 and 2, resp.), and two lactones, atractylenolides II and III (3 and 4, resp.). The structures of the compounds were elucidated based on NMR spectra. The four isolated compounds were evaluated for their insecticidal and repellent activities against T. castaneum. Atractylodin exhibited strong contact activity against T. castaneum adults with a LD50 value of 1.83 μg/adult. Atractylodin and atractylenolide II also possessed strong repellenct activities against T. castaneum adults. After 4-h exposure,90% repellency was achieved with atractylodin at a low concentration of 0.63 μg/cm(2) . The results indicated that atractylodin (1) and atractylenolide II (3) have a good potential as a source for natural repellents, and 1 has the potential to be developed as natural insecticide.

Novel amine N-halamine copolymerized polystyrene (ANHCPS) nanostructures were controllably fabricated as potent antibiotics by using the surfactant-free emulsion copolymerization for killing pathogenic bacteria. The morphology and size of the ANHCPS were well tailored by tuning reaction conditions such as monomer molar ratio, temperature, and copolymerization time. Effect of chlorination aging time on the oxidative chlorine content in the ANHCPS was established, and the oxidative chlorine content was determined by the modified iodometric/thiosulfate technique. Antibacterial behavior of the ANHCPS on bacterial strain was evaluated using Staphylococcus aureus and Escherichia coli as model pathogenic bacteria via the plate counting technique, inhibition zone study, and time-kill assay. Antimicrobial results illustrated that the ANHCPS possessed superior antibacterial capability of killing pathogenic bacteria. The destruction induced by the ANHCPS on bacterial surface structure was proven by using SEM technique. The effect of the oxidative chlorine content and morphology/size on the antimicrobial capability was constructed as well. This study provides us a novel approach for controllably synthesizing amine N-halamine polymers, and making them the potent candidates for killing bacteria or even the control of microorganism contamination.

Employing a chiral spirodiphosphine monoxide ligand with 1,1'-spirobiindane backbone (SDP(O)), a desymmetrization strategy of Pd-catalyzed intramolecular asymmetric aryl C-O coupling of 2-(2-halophenoxy)propane-1,3-diols, was developed. The SDP(O) ligand shows much better results than its SDP counterpart. The protocol provides an efficient and highly enantioselective method for the synthesis of 2-hydroxymethyl-1,4-benzodioxanes. Density functional theory studies provide a model that accounts for the origin of the enantioselectivity.

Radiation-induced brain injury (RIBI) is the most common side-effect after cranial radiation therapy (CRT). In the present study, the RIBI mice model was established and the changes in the expression of tumor necrosis factor alpha (TNF-α) and interleukin-1beta (IL-1β) mRNA, and the related signal pathways in the hippocampus of this model were investigated.10 Gy CRT or sham-irradiation was given to the three-week old mice. The water maze test was used to test the RIBI model in mice. The expression of pro-inflammatory cytokines was detected by real-time polymerase chain reaction (PCR) in vivo. The changes of microglial activation and neurogensis in the hippocampus were analyzed by immunofluorescence and immunohistochemistry. The cytoplasm to nuclei translocation of Nuclear factor kappa B (NF-κB), and the protein expressions of IkappaB-alpha (IκB-α), NF-κB essential modulator (NEMO), p53-induced protein with a death domain (PIDD), TNF-α and IL-1β were examined by Western blotting. A RIBI model was established by Morris water maze test 6 weeks after 10 Gy CRT in three-week old C57BL/6J mice.The mRNA and protein expression levels of TNF-α and IL-1β reached the peak during the early phase after CRT. Increases in cytokine levels also were observed after irradiation of mouse BV-2 microglial cells. Neurogensis was significantly inhibited in the hippocampus with an increase of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cells. The total number of microglia was decreased after CRT, but microglial activation was significantly increased. Western blotting revealed, in the RIBI mice, the expression of IκB-α was down-regulated, accompanied by the up-regulated expression of NEMO and regulated auto-proteolysis of PIDD. Also the NF-κB pathway activation was observed in BV-2 cells after irradiation.CRT-induced pro-inflammatory cytokines release in the brain tissues and inhibition of neurogenesis in the hippocampus might be contributed by the microglial activation and play an important role in RIBI.