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There is an urgent need to develop a rapid procedure that can rapidly identify and obtain antimicrobial susceptibility testing (AST) results directly from positive blood cultures. Here, we report a semi-automatic bacterial diagnosis procedure, which includes 1) a bacterial concentration process to isolate the bacteria from a positive blood culture bottle (PBCB), 2) an identification process using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), and 3) a rapid AST process based on stimulated Raman scattering imaging of deuterium oxide (D2O) incorporation in bacteria. A total of 105 samples were tested for bacterial identification, and bacterial identification accuracy of 92.3% was achieved. AST takes about 2.5 h after identification. This semi-automatic procedure only takes 3.5 h, which is demonstrated to be the fastest process to obtain identification and AST results starting from PBCB.

Semiconducting polymers usually with high photostability, reactive oxygen species (ROS) generation ability and photothermal conversion efficiency hold tremendous promise for phototherapy. In this study, a biodegradable tri-component semiconducting polymer (NDT) has been designed and synthesized for phototheranostics. NDT nanoparticles (NPs) obtained by nano-precipitation with an ultrahigh photothermal conversion efficiency (65.6%) could be degraded in the presence of hydrogen peroxide in the tumor microenvironment (TME). Such NPs show high phototoxicity towards human cervical cancer cells (HeLa) with laser irradiation as well as negligible dark toxicity. Furthermore, the in vivo study demonstrates that tumor growth was inhibited efficiently when mice were injected with NDT NPs, even with low power laser irradiation (0.2 W cm−2). In contrast, higher power density (0.5 W cm−2) led to complete tumor suppression. No side effects were observed towards normal tissues, which was confirmed by the H&E stained pictures of the normal tissues, including heart, liver, spleen, lung and kidney. Further, hematological, liver and renal function parameters indicate the biosafety of NDT NPs.

Hyperhomocysteinemia (HHcy)-related brain vascular disorders and brain endothelial dysfunction are important characteristics of the pathogeneses of subarachnoid hemorrhage and stroke. Upregulated homocysteine (Hcy) can impair the integrity of the blood-brain barrier (BBB). Opicapone has been recently licensed for the management of Parkinson's disease (PD); however, it is unknown whether it possesses a protective effect in brain vessels against HHcy. To investigate the beneficial effects of Opicapone on BBB permeability against HHcy, we carried out both in vivo and in vitro experiments. Mice were allocated into four groups: the Control, Opicapone, HHcy, and HHcy + Opicapone. Interestingly, we found that the administration of Opicapone attenuated the increased BBB permeability in Hcy-treated mice, as determined by sodium fluorescein staining. The immunofluorescence staining showed that Opicapone prevented homocysteine-induced reduction of claudin-2 in the mice cortices. The in situ zymography assay revealed that Opicapone suppressed homocysteine-increased matrix metalloproteinases (MMPs) activity in the cortices. In bEnd.3 brain endothelial cells, Opicapone treatment ameliorated homocysteine-induced lactate dehydrogenase (LDH) release and expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). Furthermore, Opicapone alleviated homocysteine-induced decrease in claudin-2 level in bEnd.3 cells. In summary, our results show that Opicapone protects against HHcy-induced BBB permeability by reducing the expression and gelatinase activity of MMPs, and increasing the expression of claudin-2.

Acquiring desirable device performance with deep-blue color purity that fulfills practical application requirements is still a challenge. Bipolar fluorescent emitters with hybrid local and charge transfer (HLCT) state may serve to address this issue. Herein, by inserting anthracene core in the deep-blue building blocks, the authors successfully developed two highly twisted D-π-A fluorescent emitters, ICz-An-PPI and IP-An-PPI, featuring different acceptor groups. Both exhibited superb thermal stabilities, high photo luminescent quantum yields and excellent bipolar transport capabilities. The non-doped OLEDs using ICz-An-PPI and IP-An-PPI as the emitting layers showed efficient blue emission with an external quantum efficiency (EQEmax ) of 4.32 % and 5.41 %, and the CIE coordinates of (0.147, 0.180) and (0.149, 0.150), respectively. In addition, the deep blue doped device based on ICz-An-PPI was achieved with an excellent CEmax of 5.83 cd A-1 , EQEmax of 4.6 % and the CIE coordinate of (0.148, 0.078), which is extremely close to the National Television Standards Committee (NTSC) standard. Particularly, IP-An-PPI-based doped device had better performance, with an EQEmax of 7.51 % and the CIE coordinate of (0.150, 0.118), which was very impressive among the recently reported deep-blue OLEDs with the CIEy

An aromatic diamine monomer containing an asymmetric pendant terphenyl group, 3,5-(diphenyl)phenyl-2,4-diaminobenzene, was synthesized based on a two-step reaction. The monomer was further reacted with three different commercial aromatic dianhydrides (3,3′,4,4′-biphenyltetracarboxylic dianhydride, 4,4′-oxydiphthalic anhydride, 3,3′,4,4′-benzophenone tetracarboxylic dianhydride) in one-step high-temperature polycondensation to prepare a series of soluble polyimides: PI 3a–3c. The chemical structure of the obtained monomer and polymers was characterized carefully, and some selective properties were investigated in detail. These polyimides exhibit excellent thermal stability and low dielectric constant and water absorption. Their glass transition temperatures (Tg) and 10% weight loss temperatures (T10%) in N2 are up to 337°C and 596°C, respectively. Their dielectric constant and water absorption are 2.64 (at 1 MHz) and 0.73%, respectively. Moreover, the polyimides also have high optical transparency. Their values are in the range of 67–81% at a wavelength of 450 nm, and the cut-off wavelengths are in the range of 343–359 nm.

This study evaluated the safety, effectiveness, and feasibility of indocyanine green (ICG) tracing in guiding lymph-node (LN) dissection during laparoscopic D2 radical gastrectomy in patients with advanced gastric cancer (AGC) after neoadjuvant chemotherapy (NAC). We retrospectively analyzed data on 313 patients with clinical stage of cT1-4N0-3M0 who underwent laparoscopic radical gastrectomy after NAC between February 2010 and October 2020 from two hospitals in China. Grouped according to whether ICG was injected. For the ICG group (n = 102) and non-ICG group (n = 211), 1:1 propensity matching analysis was used. After matching, there was no significant difference in the general clinical pathological data between the two groups (ICG vs. non-ICG: 94 vs. 94). The average number of total LN dissections was significantly higher in the ICG group and lower LN non-compliance rate than in the non-ICG group. Subgroup analysis showed that among patients with LN and tumor did not shrink after NAC, the number of LN dissections was significantly more and LN non-compliance rate was lower in the ICG group than in the non-ICG group. Intraoperative blood loss was significantly lesser in the ICG group than in the non-ICG group, while the recovery and complications of the two groups were similar. For patients with poor NAC outcomes, ICG tracing can increase the number of LN dissections during laparoscopic radical gastrectomy, reduce the rate of LN non-compliance, and reduce intraoperative bleeding. Patients with AGC should routinely undergo ICG-guided laparoscopic radical gastrectomy.

Optical imaging (OI) provides real-time clinical imaging capability and simultaneous molecular, morphological, and functional information of disease processes. In this study, we present a new interventional OI technique, which enables in vivo visualization of three distinct pathologic zones of ablated tumor periphery for immediate detection of residual tumors during a radiofrequency ablation (RFA) session. Rabbits with orthotopic hepatic tumors were divided into two groups (n = 8/group): incomplete RFA and complete RFA. Indocyanine green-based interventional OI was used to differentiate three pathological zones: ablated tumor, transition margin, and residual tumor or surrounding normal liver—with quantitative comparison of signal-to-background ratios among the three zones and between incompletely and completely ablated tumors. Subsequent ex vivo OI and pathologic correlation were performed to confirm the findings of interventional OI. Interventional OI could differentiate incompletely or completely ablated tumor peripheries, thus permitting identification of residual tumor. This technique may open new avenues for immediate assessment of tumor eradication during a single interventional ablation session. Significance: Interventional optical imaging can instantly visualize pathologic zones of ablated tumor peripheries to detect residual tumors, which could revolutionize current image-guided interventional oncologic ablation techniques.

Transition metal phosphides (TMPs) are promising anode candidates for sodium-ion batteries, due to their high theoretical specific capacity and working potential. However, the low conductivity and excessive volume variation of TMPs during insertion/extraction of sodium ions results in a poor rate performance and long-term cycling stability, largely limiting their practical application. In this paper, the NiP 2 nanoparticles encapsulated in three-dimensional graphene (NiP 2 @rGO) were obtained from the flower-like sphericalα-Ni(OH) 2 by phosphating and carbon encapsulation processes. When used as a sodium-ion batteries anode material, NiP 2 @rGO composite shows excellent cycling performance (117 mA h g -1 at 10 A g -1 after 8000 cycles). The outstanding electrochemical performance of NiP 2 @rGO is ascribed to the synergistic effect of the rGO and NiP 2 core. The rGO wrapped on the NiP 2 nanoparticles build a conductive way, improving ionic and electronic conductivity. The effective combination of NiP 2 nanoparticles with graphene greatly reduces the NiP 2 nanoparticles aggregation and pulverization during the discharge/charge process. This paper may shed light on the construct of high-performance anode material for sodium ion batteries and to other electrode materials.

In this work, the effect of the crystal structures, morphology and ion diffusion on magnetic properties of the hexagonal barium ferrite films during the annealing process were studied. The structural characterization results demonstrated that the orientation, crystallinity and morphology of the films can be controlled by the anneal temperature. Good crystallinity and morphology of the film can be annealed at a temperature ≥ 1000°C, while the formation of BaFe12−xAlxO19 phase occurred due to the ion diffusion when the annealing temperature reached 1200°C. Magnetic hysteresis loops showed that the saturation magnetization, coercivity and remanence ratio of the films were all influenced by crystal structures, morphology and ion diffusion. The platelet particle morphology and high crystallinity demonstrated a good magnetic film, but the ion diffusion mutated the magnetic parameters. Additionally, the first-order reversal curve diagram further verified that the change of crystallite sizes greatly influences the distribution of coercivity and interaction field. Consequently, the film annealed at 1000°C has a high out-of-plane c-axis orientation, high crystallinity with a full width at half maximum of 0.18° and high saturation magnetization of 358 emu/cm3, which can be applied in the microwave device.

Using a flexible bis (triazole) ligand BBPTZ, where BBPTZ = 4,4'- bis (1,2,4-triazol-1-ylmethyl) biphenyl, a novel compound of [Ni2(BBPTZ)4][β-Mo8O26] (1) based on [NiN4O2]2+ secondary building unit (SBU) and [β-Mo8O26]4– cluster was synthesized by hydrothermal method. In compound 1, the [NiN4O2]2+ SBUs serving as 2-connected joints were directly connected [β-Mo8O26]4– clusters forming 1D inorganic strips. The adjacent strips were assembled through two types of BBPTZ ligands along the c axis, giving rise to 2D layers. It exhibits not only good thermal stability but also bifunctional electrocatalytic activity. When using it as the electrocatalyst for the electrochemical sensing for bromate, it shows a broad sensor range (1.35–4.75 mM) and comparable sensitivity of 62.39 µA cm−2 mM−1. Moreover, it also exhibits a remarkable activity towards the hydrogen evolution reaction, with a 248 mV onset potential, a Tafel slope of 131 mV dec−1, and a η10 of 386 mV.

Using density functional theory and a cluster approach, we study the reaction potential surface and compute Gibbs free energies for the acylate reaction of β-lactamase with penicillin G, where the solvent effect is important and taken into consideration. Two reaction paths are investigated: one is a multi-step process with a rate-limit energy barrier of 19.1 kcal/mol, which is relatively small, and the reaction can easily occur; the other is a one-step process with a barrier of 45.0 kcal/mol, which is large and thus makes the reaction hard to occur. The reason why the two paths have different barriers is explained.

A convenient synthetic protocol for the hexasubstituted benzene derivatives was successfully developed by DABCO promoted domino reaction of arylidene malononitrile with two molecules of dialkyl but-2-ynedioates. The domino reaction resulted in tetraalkyl 6-cyano-[1,1′-biphenyl]-2,3,4,5-tetracarboxylates in good to high yields. This formal [2 + 2 + 2] cycloaddition was believed to proceed with sequential nucleophilic addition, Michael addition, annulation and aromatization processes.

High-performance deep-blue emitters with external quantum efficiencies (EQEs) exceeding 5 % are still scarce in organic light-emitting diodes (OLEDs). In this work, by introducing a [1,2,4]triazolo[1,5-a] pyridine (TP) unit at the N1 position of phenanthroimidazole (PI), two luminescent materials, PTPTPA and PTPTPA, were obtained. Systematic photophysical analysis showed that the TP block is suitable for constructing hybridized local and charge-transfer (HLCT) emitters. Its moderate electron-withdrawing ability and rigid planar structure can enhance the CT component while ensuring color purity. In addition, compared with PTPTPA, the additional phenyl ring of PTPBPTA not only increased the oscillator strength, but also decreased the Stokes shift. TDDFT calculations pointed out facile reverse intersystem crossing processes in PTPTPA from high-lying triplet states to the singlet excited state. A nondoped device based on PTPTPA as emitter showed impressive performance with EQEmax of 7.11 % and CIE coordinates of (0.15, 0.09). At the same time, it was also an efficient host for yellow and red phosphorescent OLEDs. By doping yellow (PPYBA) and red (BTPG) phosphorescent dyes into PTPTPA, a white OLED with a high EQE of 23.85 % was achieved. The successful design of PTPTPA not only provided an optimization choice for OLED emitters, but also demonstrated the empirical rules for the design of multifunctional deep-blue emitters.

Background Distant metastasis is the leading cause of death for esophageal squamous cell carcinoma (ESCC) with limited treatment options and unsatisfactory effectiveness. Bromodomain (BRD) containing proteins are emerging targets for cancer therapy with promising effects. As a unique member of BRD family, the function and molecular mechanism of ATAD2 in cancer development is seldomly investigated. Methods The clinical impact of ATAD2 was assessed both at RNA and protein level in 75 and 112 ESCC patients separately. The biological function of ATAD2 was investigated in vitro and in vivo. Signaling pathway and downstream effectors of ATAD2 were identified by RNA sequencing, luciferase reporter, co-immunoprecipitation, chromatin immunoprecipitation, immunofluorescence and western blot assay. Results We found that elevated ATAD2 expression was significantly associated with lymph node metastasis, advanced clinical stage as well as poor survival of ESCC patients. Silencing ATAD2 significantly suppressed ESCC cell migration and invasion in vitro, and inhibited tumor growth and lung metastasis in vivo. Mechanically, we identified a new cofactor, C/EBPβ. ATAD2 directly interacted with C/EBPβ and promoted its nuclear translocation, which directly bound to the promoter region of TGF-β1 and activated its expression. Further, we demonstrated that TGF-β1 activated its downstream effectors in a Smad3 dependent manner. In addition, we further found that ATAD2 promoted ESCC metastasis through TGF-β signaling induced Snail expression and the subsequent epithelial-mesenchymal transition. Conclusion Our findings demonstrated the pro-metastatic function of ATAD2 and uncovered the new molecular mechanism by regulating C/EBPβ/TGF-β1/Smad3/Snail signaling pathway, thus providing a potential target for the treatment of ESCC metastasis.

Cu-based MOFs, i.e., HKUST-1, etc., have been pertinently chosen as the pristine materials for CO2ER due to the unique ability of copper for generation hydrocarbon fuel. However, the limited conductivity and stability become the stumbling-block that prevents the development of it. The exploring of MOFs-derived M−C materials starts a new chapter for the MOFs precursors, which provides a remarkable electronic connection between carbon matrix and metals/metal oxides. N-doped M−N−C with extensive M−N sites scattering into the carbon matrix are more popular because of their impressive contribution to catalytic activity and specific product selectivity. Nevertheless, Cu–N–C system remained undeveloped up to now. The lack of ideal precursor, the sensitivity of Cu to be oxidized, and the difficulties in the synthesis of small size Cu nanoparticles are thus known as the main barriers to the development of Cu–N–C electrocatalysts. Herein, a nitrogen-rich Cu–BTT MOF is employed for the derivation of N-doped Cu–N–CT composite electrocatalysts by the pyrolyze method. High-temperature pyrolysis product of Cu–N–C1100 exhibits the best catalytic activity for productions of CO (−0.6 V vs. RHE, jCO = 0.4 mA/cm2) and HCOOH (−0.9 V vs. RHE, jHCOOH = 1.4 mA/cm2).

Transition metal selenides have been widely studied as anode materials of sodium ion batteries (SIBs), however, the investigation of solid-electrolyte-interface (SEI) on these materials, which is critical to the electrochemical performance of SIBs, remains at its infancy. Here in this paper, ZnSe@C nanoparticles were prepared from ZIF-8 and the SEI layers on these electrodes with and without reduced graphene oxide (rGO) layers were examined in details by X-ray photoelectron spectroscopies at varied charged/discharged states. It is observed that fast and complicated electrolyte decomposition reactions on ZnSe@C leads to quite thick SEI film and intercalation of solvated sodium ions through such thick SEI film results in slow ion diffusion kinetics and unstable electrode structure. However, the presence of rGO could efficiently suppress the decomposition of electrolyte, thus thin and stable SEI film was formed. ZnSe@C electrodes wrapped by rGO demonstrates enhanced interfacial charge transfer kinetics and high electrochemical performance, a capacity retention of 96.4%, after 1000 cycles at 5 A/g. This study might offer a simple avenue for the designing high performance anode materials through manipulation of SEI film.

Thirteen undescribed dihydroagarofuran sesquiterpenes, hypogricins A-M, were isolated from the twigs of Tripterygium hypoglaucum. Extensive spectroscopic techniques were used for the structural elucidation of these compounds. All the compounds showed no significant cytotoxicity against adriamycin-sensitive HepG-2 and adriamycin-resistant HepG-2/Adr cell lines. When HepG-2/Adr cell line was co-treated with those compounds plus adriamycin, hypogricins A and B showed potent activity to reverse multidrug resistance (MDR) of HepG2/Adr cells to adriamycin (reversal fold: RF = 102 and 200, respectively). In addition, hypogricins E, H, and L showed moderate activity to inhibit NO production in LPS-stimulated RAW264.7 cells with the IC50 of 22.3, 17.8, and 19.8 μM, respectively.

Kinesin superfamily protein 3C (KIF3C), a motor protein of the kinesin superfamily, is expressed in the central nervous system (CNS). Recently, several studies have suggested that KIF3C may act as a potential therapeutic target in solid tumors. However, the exact function and possible mechanism of the motor protein KIF3C in glioma remain unclear. In this study, a variety of tests including CCK-8, migration, invasion, and flow cytometry assays, and western blot were conducted to explore the role of KIF3C in glioma cell lines (U87 and U251). We found that overexpression of KIF3C in glioma cell lines promoted cell proliferation, migration, and invasion and suppressed apoptosis, while silencing of KIF3C reversed these effects. Ectopic KIF3C also increased the expression of N-cadherin, vimentin, snail, and slug to promote the epithelial-mesenchymal transition (EMT). Mechanistically, overexpression of KIF3C increased the levels of phosphatidylinositol 3-kinase (PI3K) and phosphorylated protein kinase B (p-AKT). These responses were reversed by KIF3C downregulation or AKT inhibition. Our results indicate that KIF3C promotes proliferation, migration, and invasion and inhibits apoptosis in glioma cells, possibly by activating the PI3K/AKT pathway in vitro. KIF3C might act as a potential biomarker or therapeutic target for further basic research or clinical management of glioma.

In this work, a molecularly imprinted polymers (MIPs)-based SERS sensor for selective, sensitive, quantitative and recyclable detection of paclobutrazol residue in complex environments has been pro...

The newly-discovered supergiant Huayangchuan uranium (U)-polymetallic (Sr, Se, REEs, Ba, Nb and Pb) deposit is located in the Qinling Orogen, central China. The deposit underwent multistage mineralization, with the main carbonatite ore stage being the most important for the U, Nb, REE, Sr and Ba endowments. According to the mineral assemblages, the main carbonatite ore stage can be divided into three substages, i.e., sulfate (Ba–Sr), alkali-rich U and REE-U mineralization. Main-stage titanite from the Huayangchuan igneous carbonatite are rich in high field strength elements (HFSEs, e.g., Zr, Nb and REEs), and show clear elemental substitutions (e.g., Ti vs. Nb ​+ ​Fe ​+ ​Al and Ca ​+ ​Ti vs. Fe ​+ ​Al ​+ ​REE). High-precision LA-ICP-MS titanite dating yielded a U–Pb age of 209.0 ​± ​2.9 ​Ma, which represents the main-stage mineralization age at Huayangchuan, and is coeval with the local carbonatite dyke intrusion. This mineralization age is further constrained by the Re–Os dating of molybdenite from the Huayangchuan carbonatite, which yielded a weighted mean age of 196.8 ​± ​2.4 ​Ma. Molybdenite Re contents (337.55–392.75 ​ppm) and C-O-Sr-Nd-Pb isotopic evidence of the Huayangchuan carbonatite both suggest a mantle origin for the carbonatite. Our study supports that the Late Triassic carbonatite magmatism was responsible for the world-class U-Mo-REE mineralization in the Qinling Orogen, and that the regional magmatism and ore formation was likely caused by the closure of the Mianlue ocean and the subsequent North China-South China continent-continent collision.

Calcium homeostasis modulators (CALHMs/CLHMs) comprise a family of pore‐forming protein complexes assembling into voltage‐gated, Ca2+‐sensitive, nonselective channels. These complexes contain an ion‐conduction pore sufficiently wide to permit the passing of ATP molecules serving as neurotransmitters. While their function and structure information is accumulating, the precise mechanisms of these channel complexes remain to be full understood. Here, we present the structure of the Caenorhabditis elegans CLHM1 channel in its open state solved through single‐particle cryo‐electron microscopy at 3.7‐Å resolution. The transmembrane region of the channel structure of the dominant class shows an assembly of 10‐fold rotational symmetry in one layer, and its cytoplasmic region is involved in additional twofold symmetrical packing in a tail‐to‐tail manner. Furthermore, we identified a series of amino acid residues critical for the regulation of CeCLHM1 channel using functional assays, electrophysiological analyses as well as structural‐based analysis. Our structure and function analyses provide new insights into the mechanisms of CALHM channels.

Epilepsy is a prevalent neurological disorder and it is a significant health risk, affecting >50 million people worldwide. The development of novel and appropriate strategies is required for ameliorating the progression and/or limiting the detrimental consequences of epilepsy. In the current study, kainic acid (KA), a neurotoxin, was used to induce seizures in mice. The flavonoid quercetin has recently been reported to have neuroprotective effects. Therefore, the effects of quercetin on KA-induced epilepsy and the potential underlying molecular mechanisms were examined. It was noted that quercetin attenuated the KA-induced seizure score and proinflammatory cytokine production, including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and activation of nuclear factor κB (NF-κB) in mice. Quercetin attenuated KA-induced proinflammatory cytokine (TNF-α and IL-1β) release from microglia cells, as well as activation of NF-κB and ionized calcium binding adapter molecule 1 in microglia cells. Therefore, quercetin inhibited KA-induced epilepsy by microglia cell inactivation and the production of NF-κB, TNF-α and IL-1β.

Neurofibrillary tangles (NFTs) composed of hyperphosphorylated and misfolded tau protein are a pathological hallmark of Alzheimer’s disease and other tauopathy conditions. Tau is predominantly an intraneuronal protein but is also secreted in physiological and pathological conditions. The extracellular tau has been implicated in the seeding and propagation of tau pathology and is the prime target of the current tau immunotherapy. However, truncated tau species lacking the microtubule-binding repeat (MTBR) domains essential for seeding have been shown to undergo active secretion and the mechanisms and functional consequences of the various extracellular tau are poorly understood. We report here that the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis, plays an essential role in the lysosomal exocytosis of selected tau species. TFEB loss of function significantly reduced the levels of interstitial fluid (ISF) tau in PS19 mice expressing P301S mutant tau and in conditioned media of mutant tau expressing primary neurons, while the secretion of endogenous wild-type tau was not affected. Mechanistically we found that TFEB regulates the secretion of truncated mutant tau lacking MTBR and this process is dependent on the lysosomal calcium channel TRPML1. Consistent with the seeding-incompetent nature of the truncated tau and supporting the concept that TFEB-mediated lysosomal exocytosis promotes cellular clearance, we show that reduced ISF tau in the absence of TFEB is associated with enhanced intraneuronal pathology and accelerated spreading. Our results support the idea that TFEB-mediated tau exocytosis serves as a clearance mechanism to reduce intracellular tau under pathological conditions and that effective tau immunotherapy should devoid targeting these extracellular tau species.

The three-component reaction of triphenylphosphine, dimethyl hex-2-en-4-ynedioate and arylidene N,N'-dimethylbarbituric acids in dry methylene dichloride at room temperature afforded trans-1,3-disubstituted 7,9-diazaspiro[4.5]dec-1-enes in good yields and with high diastereoselectivity. However, the similar three-component reaction with arylidene Meldrum acids resulted in a mixtures of cis/trans-1,2-disubstituted 7,9-dioxaspiro[4.5]dec-1-enes. Additionally, the three-component reaction of triphenylphosphine, dimethyl but-2-ynedioate and arylidene Meldrum acids gave polysubstituted 5-(triphenyl-λ5-phosphanylidene)cyclopenta-1,3-dienes. A plausible reaction mechanism was proposed for the formation of various products with different regioselectivity and diastereoselectivity.

Inflammatory bowel disease (IBD) involves chronic inflammation, loss of epithelial integrity, and gastrointestinal microbiota dysbiosis. Effective therapies for IBD have not been established. Accordingly, in this study, we evaluated the effects of inorganic nitrate, a potent nitric oxide (NO) donor and microbiota regulator, in a mouse model of dextran sodium sulfate (DSS)-induced colitis. Mice were pretreated with NaNO3 (2 mM) in their drinking water for 5 days, and NaCl was used as a control. Feces were collected for microbiota analyses. The results showed that oral administration of dietary nitrate could maintained colon consistency, improved colon length, maintained body weight, decreased apoptosis in colon epithelial cells, and ameliorated inflammatory cell infiltration in both the colon and peripheral blood. Microbiota profiling revealed that nitrate regulated dysbiosis. Analysis of the top bacteria at the genus level showed that Bacteroidales_S24-7_group_unidentified, Lactobacillus, Bacteroides, and Prevotellaceae_UCG-001 decreased in the DSS group compared with that in the normal group, whereas Lactobacillus, Ruminococcaceae_UCG-014, and Prevotellaceae_UCG-001 were increased in the DSS + NaNO3 group compared with that in the DSS group. The enriched bacteria in the nitrate group included Gordonibacter, Ureaplasama, and Lachnospiraceae_UCG-006. Moreover, microbiota analysis revealed that nitrate could partially decrease the enriched metabolic pathways (p53 signaling pathway and colorectal cancer pathway) compared with that in the DSS and DSS + NaCl groups. Overall, these findings indicated that nitrate could ameliorate DSS-induced colitis by decreasing inflammation, reducing apoptosis, and regulating the microbiota by activation of the NO3−/NO2−/NO pathway. Nitrate might be a potential treatment for colitis patients in the future clinical application.

As an important part of biogeochemical cycling, the nitrogen cycle modulates terrestrial ecosystem carbon storage, water consumption, and environmental quality. Modeling the complex interactions between nitrogen, carbon and water at a regional scale remains challenging. Using China as a testbed, this study presents the first application of the nitrogen-augmented community Noah land surface model with multi-parameterization options (Noah-MP-CN) at the regional scale. Noah-MP-CN parameterizes the constraints of nitrogen availability on photosynthesis based on the Fixation and Uptake of Nitrogen plant nitrogen model and the Soil and Water Assessment Tool soil nitrogen model. The impacts of nitrogen dynamics on the terrestrial carbon and water cycles are investigated by comparing the simulations with those from the original Noah-MP. The results show that incorporating nitrogen dynamics improves the carbon cycle simulations. Noah-MP-CN outperforms Noah-MP in reproducing leaf area index (LAI) and gross primary productivity (GPP) for most of China, especially in the southern warm and humid regions, while the hydrological simulations only exhibit slight improvements in soil moisture and evapotranspiration. The impacts of fertilizer application over cropland on carbon fixation, water consumption and nitrogen leaching are investigated through a trade-off analysis. Compared to halved fertilizer use, the actual quantity of application increases GPP and water consumption by only 1.97% and 0.43%, respectively; however, the nitrogen leaching is increased by 5.35%. This indicates that the current level of fertilizer use is a potential concern for degrading the environment.

Transition metal phosphides have received extensive attention as anode materials of sodium ion batteries due to their high theoretical specific capacity and low redox potentials. However, the large volume change during the insertion/extraction of sodium ions often leads to a poor electrochemical performance and thus limits their practical application. Herein, we rationally designed three-dimensional hierarchical Ni5P4 nanospheres wrapped by rGO nanostructures (Ni5P4@rGO) through a sequential hydrothermal synthesis and phosphidation of highly folded spherical α-Ni(OH)2. The graphene nanosheets can effectively prevent the collapse of spherical α-Ni(OH)2 and aggregation of Ni5P4 active materials during phosphidation. Besides, the strong coupling between the nickel phosphide and graphene layers leads to excellent electrochemical performance of Ni5P4@rGO composite as anode materials of SIBs, delivering a specific capacity of 304 mA h g–1 at 0.2 A g–1 after 200 cycles. The strategy developed in this paper may shed light on the morphology-controlled synthesis of transition metal phosphides with high performance for energy storage devices.

Chaperone-mediated autophagy (CMA) serves as a critical upstream regulator of lipophagy and lipid metabolism in hepatocyte. However, the role of CMA in lipid metabolism of macrophage, the typical component of atherosclerotic plaque, remains unclear. In our study, LAMP-2A (L2A, a CMA marker) was reduced in macrophages exposed to high dose of oleate, and lipophagy was impaired in advanced atherosclerosis in ApoE (−/−) mice. Primary peritoneal macrophages isolated from macrophage-specific L2A-deficient mice exhibited pronounced intracellular lipid accumulation. Lipid regulatory enzymes, including long-chain-fatty-acid-CoA ligase 1 (ACSL1) and lysosomal acid lipase (LAL), were increased and reduced in L2A-KO macrophage, respectively. Other lipid-related proteins, such as SR-A, SR-B (CD36), ABCA1, or PLIN2, were not associated with increased lipid content in L2A-KO macrophage. In conclusion, deficient CMA promotes lipid accumulation in macrophage probably by regulating enzymes involved in lipid metabolism. CMA may represent a novel therapeutic target to alleviate atherosclerosis by promoting lipid metabolism. Graphical abstract Electronic supplementary material The online version of this article (10.1007/s12265-020-09986-3) contains supplementary material, which is available to authorized users.

Binary transition metal selenides have been more promising than single transition metal selenides as anode materials for sodium-ion batteries (SIBs). However, the controlled synthesis of transition metal selenides, especially those derived from metal-organic-frameworks with well-controlled structure and morphology is still challenging. In this paper, highly porous NiCoSe4 @NC composite microspheres were synthesized by simultaneous carbonization and selenization of a Ni-Co-based metal-organic framework (NiCo-MOF) and characterized by scanning electron microscopy, transition electron microscopy, X-Ray diffraction, X-Ray photoelectron spectroscopy and electrochemical techniques. The rationally engineered NiCoSe4 @NC composite exhibits a capacity of 325 mAh g-1 at a current density of 1 A g-1 , and 277.8 mAh g-1 at 10 A g-1 . Most importantly, the NiCoSe4 @NC retains a capacity of 293 mAh g-1 at 1 A g-1 after 1500 cycles, with a capacity decay rate of 0.025 % per cycle.

The abilities of opioids to activate downstream signaling pathways normally depend on the binding between opioids and their receptors. However, opioids may also function in a receptor-independent manner, especially in neural stem cells (NSCs) in which the expression of opioid receptors and endogenous opioid agonists is low. When two opioids, morphine and naloxone, were used during the early stage of NSC differentiation, increased neurogenesis was observed. However, naloxone methiodide, a membrane impenetrable analog of naloxone, did not affect the NSC differentiation. The abilities of morphine and naloxone to facilitate neurogenesis were also observed in opioid receptor-knockout NSCs. Therefore, morphine and naloxone promote neurogenesis in a receptor-independent manner at least during the early stage. In addition, the receptor-independent functions of opioids were not observed in methylcytosine dioxygenase ten-eleven translocation 1 (Tet1) knockout NSCs. When the expression of opioid receptors increased and the expression of Tet1 decreased during the late stage of NSC differentiation, morphine, but not naloxone, inhibited neurogenesis via traditional receptor-dependent and miR181a-Prox1-Notch-related pathway. In summary, the current results demonstrated the time-dependent effects of opioids during the differentiation of NSCs and provided additional insight on the complex functions of opioids.

Background Mitochondria play a critical role as effectors and targets of brain injury in the post-resuscitation period. Although we found previously that the extracellular signal-regulated kinase (ERK)1/2 inhibitor PD98059 (PD) protects the brain against mitochondrial-mediated cell death at 24 h post-resuscitation in rats subjected to cardiac arrest/cardiopulmonary resuscitation (CA/CPR), it is not clear whether PD also exerts mitochondrial protective effect for a lasting time. Therefore, we examined the effect of PD on brain mitochondria at 48 h post-resuscitation to evaluate the time-effect of PD in the current study. Methods Experimental rats were divided randomly into 5 groups: Sham, CA, dimethylsulfoxide (DMSO), 0.15mg/kg PD and 0.3mg/kg PD. Rats except for sham group were subjected to CA for 6 min followed by CPR. We detected survival rates and neurologic deficit scores, cerebral cortex mitochondrial function by evaluating adenosine triphosphate (ATP) levels, mitochondrial permeability transition pore (MPTP) opening, and the expression of mitofusin2 (Mfn2) and observing the ultrastructure by electron microscopy at 48 h post-resuscitation in a 6-min CA rat model. Results PD improved survival rates and neurologic deficit scores, alleviated cerebral cortex mitochondrial damage by reducing MPTP opening and increasing Mfn2 production at 48 h post-resuscitation in a 6-min CA rat model. Conclusion A single dose of PD improved 48 h post-resuscitation outcome and mitochondrial function, indicating the potential of the use of ERK inhibitors for the treatment of brain injury resulting from CA in the future.

Corneal stromal fibroblasts are connected to each other via gap junctions, which contribute to maintenance of corneal homeostasis. Viral infection of the corneal stroma can result in inflammation and scarring. The effects of polyinosinic-polycytidylic acid [poly(I:C)], an analog of viral double-stranded RNA, on gap junctional intercellular communication (GJIC) in cultured human corneal fibroblasts (HCFs) were examined.Cultured HCFs were exposed to poly(I:C) in the absence or presence of inhibitors of mitogen-activated protein kinase (MAPK) signaling or the antioxidantExposure of HCFs to poly(I:C) resulted in down-regulation of Cx43 expression and GJIC activity as well as in up-regulation of microRNA-21 expression. Poly(I:C) increased the amount of malondialdehyde and reduced the activity of SOD in the cells, and these effects were prevented by NAC. The inhibitory effects of poly(I:C) on both Cx43 expression and GJIC activity were attenuated by NAC and by c-Jun NHPoly(I:C) inhibited Cx43 expression and GJIC in cultured HCFs, possibly as a result of the associated up-regulation of microRNA-21. Poly(I:C) also increased oxidative stress in these cells, and such stress together with signaling by the MAPK JNK was implicated in the effects of poly(I:C) on Cx43 expression and GJIC activity. Down-regulation of GJIC activity among corneal fibroblasts by double-stranded RNA may thus contribute to the disruption of stromal homeostasis during viral infection of the cornea.

The identification of relevant impurities in the precursor chloroephedrine of the illegal drug methamphetamine will help for regulating this illegal drug and finding its sources. An efficient and effective method for qualitatively analysing samples of the drug was developed using high-performance liquid chromatography-hybrid ion trap/time-of-flight mass spectrometry (HPLC-IT/TOF MS). The chloroephedrine fragmentation pathway was proposed using HPLC-MSn. Two impurities (1R, 2S)-β-chloro-methamphetamine and N-(1-phenyl-allyl)-β-chloro-methamphetamine in chloroephedrine samples were identified by the optimized HPLC-IT/TOF-MS. The synthetic route of the chloroephedrine samples was proposed by the analysis of these impurities. The established method would make it easy to identify impurities and find the source of this illegal drug. In addition, a method for the preparation of a chloroephedrine reference standard from actual samples was developed using preparative HPLC. The purity of the obtained standards was 99.51%.

The eCO2RR activity is correlated to the internal structural character of the catalyst. We employed two types of structural models of porphyrin-based MOFs of PCN-222(Cu) and PCN-224(Cu) into heterogeneous catalysis to illustrate the effect of structural factors on the eCO2RR performance. The composite catalyst PCN-222(Cu)/C displays better activity and selectivity (η = 450 mV, FEHCOOH = 44.3%, j = 3.2 mA cm−2) than PCN-224(Cu)/C (η = 450 mV, FEHCOOH = 34.1%, j = 2.4 mA cm−2) for the CO2 reduction to HCOOH in the range of −0.7–−0.9 V (vs. RHE) due to its higher BET surface area, CO2 uptake, and a larger pore diameter. It is interesting that PCN-224(Cu)/C displays better performance in the range of −0.4–−0.6 V (vs. RHE) due to its greater heat of adsorption, Qst and a higher affinity for CO2 molecule, which could promote the capture of CO2 onto the exposed active sites. As a result, PCN-224(Cu)/C exhibits better stability for the long-term electrolysis.

A new quaternary oxygen-free cobalt-based compound, SmCoAsF, which crystallizes with a tetragonal ZrCuSiAs-type structure, was synthesized via a solid state metathesis (SSM) reaction. The lattice constants a and c of SmCoAsF were 3.9555(0) A and 8.2462(2) A, respectively. Based on the measurements of electrical resistivity and magnetization, it was inferred that the as-synthesized sample mainly underwent a ferromagnetic (FM) transition at Tc ∼ 70 K, followed by an antiferromagnetic (AFM) transition at a lower temperature, TN1 ∼ 40 K. The third magnetic transition at TN2 ∼ 6 K was also observed clearly in the magnetic measurements. SmCoAsF with a rich magnetic phase is expected to be a new member of the quaternary cobalt-based system and contribute to the explorations of the origin of magnetic state transitions.

In this investigation, we demonstrated a controlled electrodeposition method by varying the current density to generate hierarchical structures of zinc (Zn) on a carbon steel surface, which serves as a hydrophobic and anticorrosion coating when further modified by stearic acid to form a covalently bonded layer that offers low surface energy. The chemical composition, surface morphology and roughness of the modified Zn coatings were analyzed via X-ray photoelectron spectroscopy (XPS), field emission scanning electron microscopy (FESEM), and confocal laser scanning microscopy (CLSM). The water contact angle and wettability tests have shown that the modified Zn coating with a micro/nanostructure displayed a water contact angle of 158.7° and a sliding angle of 6.4°, indicating strong superhydrophobicity. Interestingly, the modified Zn coating with a micro/nanostructure exhibited strong mechanical stability during knife scratching and adhesive tape peeling tests. In addition, the modified superhydrophobic Zn coating showed improved corrosion resistance that provided protection to the carbon steel. The protection mechanism can be attributed to the hierarchical micro/nanostructure of the Zn surface itself and the formation of a hydrophobic zinc stearate complex compound. The superhydrophobic Zn coating has good application prospects in a neutral corrosion environment, where it retards corrosion and reduces the adhesion of water.

A novel and highly efficient ternary H2SrTa2O7/g-C3N4/Ag3PO4 heterojunction was fabricated via simple impregnation and ion exchange methods with active performance for the degradation of methyl orange (MO) under solar-like irradiation. The optimal result for the binary composite was obtained for a H2SrTa2O7/g-C3N4-60 wt% system. The incorporation of Ag3PO4 led to a further improvement in the photocatalytic performance, as compared to the binary composite and their single components, with values of around 45.18, 44.17 and 38.23 times higher than those of pristine H2SrTa2O7, g-C3N4 and H2SrTa2O7/g-C3N4, respectively. It was found that MO solution (20 mg L−1) could be photo-degraded within 8 min with 50 mg of the H2SrTa2O7/g-C3N4/Ag3PO4 composite. This enhanced photocatalytic behavior can be mainly ascribed to the prominently promoted charge separation efficiency, the matched band-edge positions, the extension of the absorption range and the synergistic effect among H2SrTa2O7, g-C3N4 and Ag3PO4. In addition, X-ray photoelectron spectroscopy and Raman spectroscopy results confirmed a strong interface interaction between H2SrTa2O7, g-C3N4 and Ag3PO4, which greatly promoted the photocatalytic activity due to the improved separation of photoinduced charge carriers. This work presents a plausible mechanism via active species trapping experiments and electron spin resonance measurements demonstrated that photogenerated holes (h+) and superoxide radicals (˙O2−) play a crucial role in the photodegradation reaction under visible light irradiation. Thus, the proposed synthetic method for the fabrication of H2SrTa2O7/g-C3N4/Ag3PO4 with superior photocatalytic activity provides new insights for the design of ternary photocatalysts with an ideal heterojunction and wide spectral response.

In this work, a method for the determination of berberine in Rhizoma coptidis using β-cyclodextrin-sensitized fluorescence technology is established. Berberine is the main extract of Rhizoma coptidis, a medicinal material, which causes an envelope reaction with β-cyclodextrin to generate fluorescence sensitization. In the environment of its own aqueous extract, with 0.0065 mol L−1 of β-cyclodextrin, a fluorescence excitation wavelength (λex) of 345 nm and an emission wavelength (λem) of 540 nm were selected to avoid interference from other distractors. The fluorescent sensor for the detection of berberine exhibits a low limit of detection (3.59 × 10−9 mol L−1) and a wide linear range from 2.7 × 10−7 mol L−1 to 2.7 × 10−6 mol L−1. Our sensor can be also used to detect berberine in real medicinal materials. The content of berberine in Rhizoma coptidis medicinal material was found to be 7.60% using this method with an average recovery rate of 99.5%. The result obtained by thin-layer chromatography with fluorescence detection was 7.61%, which is consistent with the result from the β-cyclodextrin sensitized fluorescence method. This method is simple and environmentally friendly with high sensitivity and good selectivity and gives reliable results, which is promising for practical application.

Aims: This study aimed to investigate the clinical value of induction chemotherapy (IC) with docetaxel, 5-fluorouracil plus nedaplatin followed by concurrent chemoradiotherapy (CCRT) with nedaplatin for locoregional advanced nasopharyngeal carcinoma (NPC). Materials and Methods: In total, 269 patients diagnosed with locoregional advanced NPC between June 2012 and June 2017 were retrospectively included and divided into two groups: IC (docetaxel plus nedaplatin and 5-fluorouracil) followed by nedaplatin-based CCRT (TNF + N group, n = 146) and IC (docetaxel plus cisplatin and 5-fluorouracil) followed by cisplatin-based CCRT (TPF + P group, n = 123). The Kaplan-Meier method and Cox proportional hazards model were applied to analyse survival and prognosis. After propensity score-matched (PSM), 113 patients remained in each group. Toxicities were compared between the two groups using the Chi-square test or Fisher's exact test. Results: The overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) rates of the TNF + N and TPF + P groups were 90.7% vs. 92.3% (P = 0.315), 78.9% vs. 79.4% (P = 0.715), 82.4% vs. 85.1% (P = 0.441) and 96.1% vs. 93.3% (P = 0.414), respectively, with no significant difference in 3-year survival outcome between the two groups, and this outcome was confirmed after using PSM analyses. In the PSM cohort, a significant higher frequency of grade 3/4 vomiting was observed in the TPF + P group compared to the TNF + N group (22.1% vs. 0%, P = 0.000). However, 15.9% of patients in the TNF + N group had grade 3/4 thrombocytopenia in comparison with 6.2% in the TPF + P group (P = 0.020). Conclusions: The TNF regimen followed by CCRT with nedaplatin is an alternative treatment strategy to the standard TPF regimen followed by CCRT with cisplatin for patients with locoregional advanced NPC.

Background This study was conducted to explore whether the effect of edaravone (5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol3-one, EDR) can ameliorate renal warm ischemia-reperfusion injury (IRI) by modulating endoplasmic reticulum stress (ERS) and its downstream effector after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) in a rat model. Methods The rats (n=10) experienced anaesthesia and intubation followed by no CA inducement were defined as the Sham group. Transoesophageal alternating current stimulation was employed to establish 8 min of CA followed by conventional CPR for a resuscitation model. The rats with successful restoration of spontaneous circulation (ROSC) randomly received EDR (3 mg/kg, EDR group, n=10) or equal volume normal saline solution (the NS group, n=10). At 24 hr after ROSC, serum creatinine (SCR), blood urea nitrogen (BUN) levels, and cystatin-C (Cys-C) levels were determined and the protein level of glucose-regulated protein (GRP78), C/EBP homologous protein (CHOP), extracellular signal-regulated kinase (ERK), phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), Bax/Bcl-2, and caspase-3 were detected by Western blot method. Results At 24 hrs after ROSC, SCR, BUN and Cys-C were obviously increased and the proteins expression, including GRP78, CHOP and p-ERK1/2, cleaved-caspase 3 Bax/Bcl-2 ratio, were significantly upregulated in the NS group compared with the Sham group (p