Synthesis Strategies and Applications for Pitch-Based Anode: From Industrial By-Products to Power Sources.

It is significant for saving energy to manufacture superb-property batteries. Carbon is one of the most competitive anode materials in batteries, but it is hard for commercial graphite anodes to meet the increasingly higher energy-storage requirements. Moreover, the price of other better-performing carbon materials (such as graphene) is much higher than graphite, which is not conducive to massive production. Pitch, the cheap by-product in the petroleum and coal industries, has high carbon content and yield, making it possible for commercialization. Developing pitch-based anodes can not only lower raw material costs but also realize the pitch's high value-added utilization. We comprehensively reviewed the latest synthesis strategies of pitch-derived materials and then introduced their application and research progress in lithium, sodium, and potassium ion batteries (LIBs, SIBs, and PIBs). Finally, we summarize and suggest the pitch's development trend for anodes and in other fields.

Chinese medicine Tongxinluo capsule protects against blood-brain barrier disruption after ischemic stroke by inhibiting the low-density lipoprotein receptor-related protein 1 pathway in mice.

BACKGROUND: Chinese medicine Tongxinluo capsule (TXL) has been extensively used to treat ischemic stroke in China, and one of its mechanisms is to protect against blood brain barrier (BBB) disruption after stroke. However, the underlying protective mechanisms are not fully illuminated. It is reported that the low-density lipoprotein receptor-related protein 1 (LRP-1) is involved in BBB disruption after brain ischemia. In this study, we explored whether TXL could downregulate LRP-1 expression and subsequently protect against BBB disruption after stroke using permanent middle cerebral artery occlusion (pMCAO) in mice. METHODS: The animal model of ischemic stroke was induced by pMCAO in male adult C57BL/6J mice. The mice were orally administered TXL (3.0 g/kg) at 1, 3 and 21 h after pMCAO. Meanwhile, the LRP-1 antagonist receptor associated protein (RAP) was intracerebroventricularly injected at 1 and 21 h after stroke. We measured the following parameters at 6 and 24 h: LRP-1 protein level, BBB leakage, and the expression of tight junction (TJ) proteins including occludin, claudin-5 and zonula occludens-1 (ZO-1). RESULTS: Our results showed that TXL downregulated LRP-1 level, upregulated these TJ proteins level, and reduced BBB leakage in peri-infarct regions after pMCAO. Further study found that the inhibitor RAP played the same role as did TXL in upregulating these TJ proteins level and reducing BBB leakage after stroke. CONCLUSION: Our study demonstrates that TXL protects against BBB disruption after stroke via inhibiting the LRP-1 pathway.

Ginsenoside CK-loaded self-nanomicellizing solid dispersion with enhanced solubility and oral bioavailability.

Ginsenoside compound K (CK) is a major ginsenoside metabolite of protopanaxadiol, which exhibits numerous pharmacological activity such as cardioprotective and antidiabetic. However, the therapeutic application of CK is hampered by its physicochemical characteristics and low oral bioavailability (BA). The present work aims at the preparation of CK to improve its dissolution and enhance the oral BA for the management of arrhythmia by using self-nanomicellizing solid dispersion system (SSD). The formulations were characterized by advanced techniques like DSC, XRD, FTIR, SEM and XRD. In the in vivo pharmacokinetic study, UPLC-MS/MS was used to measure the concentration of CK in plasma. Mapping Lab was applied in the experiment of perfused intact hearts to determine the ventricular rate and ventricular conduction velocity. The solubility of CK-SSD8 was 4658.11 ± 6.66 µg/ml, which is 130-fold than free CK, and the dissolution rate was faster than any other dosage forms. The average diameters of CK-SSD were smaller than 100 nm. The in vivo pharmacokinetic study revealed that the AUC(0-24) of CK-SSD8 formulation was 2.02-fold higher than pure CK. Moreover, the study performed to evaluate the efficiency in arrhythmia treatment showed a reduced ventricular rate and ventricular conduction velocity. Thus, CK-SSD could serve as potential carrier candidate in improving the clinical application of CK.

Natural Product Bis-Intercalator Depsipeptides as a New Class of Payloads for Antibody-Drug Conjugates.

A potent class of DNA-damaging agents, natural product bis-intercalator depsipeptides (NPBIDs), was evaluated as ultrapotent payloads for use in antibody-drug conjugates (ADCs). Detailed investigation of potency (both in cells and via biophysical characterization of DNA binding), chemical tractability, and in vitro and in vivo stability of the compounds in this class eliminated a number of potential candidates, greatly reducing the complexity and resources required for conjugate preparation and evaluation. This effort yielded a potent, stable, and efficacious ADC, PF-06888667, consisting of the bis-intercalator, SW-163D, conjugated via an N-acetyl-lysine-valine-citrulline- p-aminobenzyl alcohol- N, N-dimethylethylenediamine (AcLysValCit-PABC-DMAE) linker to an engineered variant of the anti-Her2 mAb, trastuzumab, catalyzed by transglutaminase.

Qiliqiangxin Attenuates Oxidative Stress-Induced Mitochondrion-Dependent Apoptosis in Cardiomyocytes via PI3K/AKT/GSK3ß Signaling Pathway.

Qiliqiangxin capsule (QLQX) is a well-known traditional Chinese medicine that exhibits cardioprotective effects in heart failure patients. However, it remains unclear whether and by which mechanism QLQX attenuates oxidative stress-induced mitochondria-dependent myocardial apoptosis. In vivo, Sprague Dawley (SD) rats received left anterior descending coronary artery ligation for 4 weeks to establish a model of heart failure after acute myocardial infarction, and then were treated with QLQX for another 4 weeks. We evaluated cardiac function, oxidative stress injury, as well as the expressions of mitochondria-dependent apoptosis and its signaling factors. The results indicated that QLQX protected cardiac function and attenuated oxidative stress-induced myocardial apoptosis. Meanwhile, QLQX elevated the Bcl-2 expression, declined the expressions of Bax, cytochrome c, apoptotic protease activating factor-1 (Apaf-1), cleaved-caspase 9 and cleaved-caspase 3, and up-regulated the ratios of phospho-AKT/AKT and phospho-glycogen synthase kinase-3ß (GSK3ß)/GSK3ß. In vitro, H9c2 cardiomyocytes were pretreated with QLQX, then exposed to H2O2 for 24 h. QLQX promoted the proliferation of H9c2 cardiomyocytes induced by H2O2 and reversed oxidative stress damage. Moreover, QLQX inhibited the apoptosis rate and the pro-apoptosis protein expressions, but improved the Bcl-2 expression as well as the ratios of phospho-AKT/AKT and phospho-GSK3ß/GSK3ß. Meanwhile, it further ameliorated mitochondrion-related apoptosis by inhibiting the mitochondrial fission, mitochondrial permeability transition pore (MPTP) opening, and mitochondrial membrane potential (MMP) decline in H9c2 cardiomyocytes induced by H2O2. In addition, all the effects of QLQX on H2O2-induced mitochondria-dependent apoptosis could be blocked by the phosphoinositide 3-kinase (PI3K) inhibitor, LY294002. We conclude that QLQX may ameliorate oxidative stress-induced mitochondria-dependent apoptosis in cardiomyocytes through PI3K/AKT/GSK3ß signaling pathway.

LncRNA MALAT1 modulates ox-LDL induced EndMT through the Wnt/ß-catenin signaling pathway.

BACKGROUND: Endothelial-to-mesenchymal transition (EndMT) plays significant roles in atherosclerosis, but the regulatory mechanisms involving lncRNAs remain to be elucidated. Here we sort to identify the role of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in ox-LDL-induced EndMT. METHODS: The atherosclerosis model was established by feeding ApoE-/- mice with high-fat diet, and the levels of lncRNA MALAT1 in mouse arterial tissue were detected by RT-qPCR. Cell model was established by treating human umbilical vein endothelial cells (HUVECs) with ox-LDL, and the levels of EndMT markers, such as CD31, vWF, α-SMA and Vimentin and lncRNA MALAT1 levels were detected and their correlations were analyzed. The role of MALAT1 in EndMT and its dependence on Wnt/ß-catenin signaling pathway was further detected by knocking down or overexpressing MALAT1. RESULTS: MALAT1 was upregulated in high-fat food fed ApoE-/- mice. HUVECs treated with ox-LDL showed a significant decrease in expression of CD31 and vWF, a significant increase in expression of α-SMA and vimentin, and upregulated MALAT1. An increased MALAT1 level facilitated the nuclear translocation of ß-catenin induced by ox-LDL. Inhibition of MALAT1 expression reversed nuclear translocation of ß-catenin and EndMT. Moreover, overexpression of MALAT1 enhanced the effects of ox-LDL on HUVEC EndMT and Wnt/ß-catenin signaling activation. CONCLUSIONS: Our study revealed that the pathological EndMT required the activation of the MALAT1-dependent Wnt/ß-catenin signaling pathway, which may be important for the onset of atherosclerosis. TRIAL REGISTRATION: Not applicable.

Chinese medicine Tongxinluo capsule alleviates cerebral microcirculatory disturbances in ischemic stroke by modulating vascular endothelial function and inhibiting leukocyte-endothelial cell interactions in mice: A two-photon laser scanning microscopy study.

OBJECTIVE: The aim of this study was to examine the effect of TXL, a Chinese medicine prescription, on cerebral microcirculatory disturbances after pMCAO in mice using TPLSM and further explore the underlying mechanisms. METHODS: Adlut male C57BL/6J mice were subjected to pMCAO and orally administered with TXL (3.0, 1.5 and 0.75 g/kg/d) at 1, 3, and 21 hours after pMCAO. The following parameters were examined at 6 and 24 hours after pMCAO: neurological deficits, infarct volume, BBB permeability, cerebral microvessel structure, brain microcirculation (TPLSM imaging), vasoactive factors, and adhesion molecules. RESULTS: TXL improved neurological deficits, reduced infarct volume, attenuated BBB disruption, protected cerebral microvessel structure, increased cerebral capillary flow velocity and volume flux, and inhibited leukocyte-endothelial cell interactions at 6 or 24 hours after pMCAO. The therapeutic efficacy was exerted in a dose-dependent manner. Further study revealed that TXL (high dose) regulated the expression of PGI2, TXA2, and ET-1, and suppressed ICAM-1 and P-selectin. CONCLUSIONS: TXL alleviates cerebral microcirculatory disturbances against ischemic injury by modulating endothelial function and inhibiting leukocyte-endothelial cell interactions. These effects are associated with regulating the expression of PGI2, TXA2, and ET-1, and suppressing ICAM-1 and P-selectin expression.

Evolution properties of polarization states of far-zone electromagnetic field scattered from an anisotropic medium.

Within the accuracy of the first-order Born approximation, expressions are derived for the cross-spectral density matrix of the electromagnetic field scattered from a three-dimensional (3D), spatially anisotropic medium. By using the analytical forms of the spectral degree of polarization (SDOP), semi-major axis, semi-minor axis, and orientation angle of the polarization ellipse, we illustrate the evolution properties of the polarization states of the far-zone scattered field. Dependences of the polarization ellipses on different combinations of correlation lengths of the medium and polarization of incident plane wave are also revealed through numerical simulations. It is shown that the polarization ellipse of the scattered field can be either stretched or squeezed along certain scattering angles, strongly depending on the anisotropic statistics of medium and polarization of incident plane wave. Our results substantially enrich the study on the reciprocal relations between the far-zone scattered properties and correlation statistics of a spatially anisotropic medium.

Design, Synthesis and Evaluation of Naphthalimide Derivatives as Potential Anticancer Agents for Hepatocellular Carcinoma.

Two kinds of naphthalimide derivatives were synthesized and evaluated for in vitro their anti-hepatocellular carcinoma properties. Compound 3a with a fused thiazole fragment to naphthalimide skeleton inhibited cell migration of SMMC-7721 and HepG2, and further in vivo trials with two animal models confirmed that compound 3a moderately inhibited primary H22 tumor growth (52.6%) and potently interrupted lung metastasis (75.7%) without obvious systemic toxicity at the therapeutic dose. Mechanistic research revealed that compound 3a inhibited cancerous liver cell growth mostly by inducing G2/M phase arrest. Western blotting experiments corroborated that 3a could up-regulate the cell cycle related protein expression of cyclin B1, CDK1 and p21, and inhibit cell migration by elevating the E-cadherin and attenuating integrin α6 expression. Our study showed that compound 3a is a valuable lead compound worthy of further investigation.

Biosynthetic engineering and fermentation media development leads to gram-scale production of spliceostatin natural products in Burkholderia sp.

A key challenge in natural products drug discovery is compound supply. Hundreds of grams of purified material are needed to advance a natural product lead through preclinical development. Spliceostatins are polyketide-nonribosomal peptide natural products that bind to the spliceosome, an emerging target in cancer therapy. The wild-type bacterium Burkholderia sp. FERM BP-3421 produces a suite of spliceostatin congeners with varying biological activities and physiological stabilities. Hemiketal compounds such as FR901464 were the first to be described. Due to its improved properties, we were particularly interested in a carboxylic acid precursor analog that was first reported from Burkholderia sp. MSMB 43 and termed thailanstatin A. Inactivation of the iron/α-ketoglutarate-dependent dioxygenase gene fr9P had been shown to block hemiketal biosynthesis. However, a 4-deoxy congener of thailanstatin A was the main product seen in the dioxygenase mutant. We show here that expression of the cytochrome P450 gene fr9R is a metabolic bottle neck, as use of an l-arabinose inducible system led to nearly complete conversion of the 4-deoxy analog to the target molecule. By integrating fermentation media development approaches with biosynthetic engineering, we were able to improve production titers of the target compound >40-fold, going from the starting ~60 mg/L to 2.5 g/L, and to achieve what is predominantly a single component production profile. These improvements were instrumental in enabling preclinical development of spliceostatin analogs as chemotherapy.

Correlation between intensity fluctuations of electromagnetic waves scattered from a spatially quasi-homogeneous, anisotropic medium.

Within the validity of the first-order Born approximation, expressions are derived for the correlation between intensity fluctuations (CIF) of an electromagnetic plane wave scattered from a spatially quasi-homogeneous (QH), anisotropic medium. Upon establishing the correlation matrix of the scattering potential of the medium, we show that the CIF is the summation of Fourier transforms of the strengths and normalized correlation coefficients (NCCs) of the scattering potential matrix. Numerical results reveal that the CIF is susceptible to the effective width and correlation length of the medium, and degree of polarization of the incident electromagnetic wave. Our study not only extends the current knowledge of the CIF of a scattered field but also provides an important reference to the study of high-order intensity correlations of light scattered from a spatially anisotropic medium.

Design, synthesis and evaluation of novel 7-aminoalkyl-substituted flavonoid derivatives with improved cholinesterase inhibitory activities.

A novel series of 7-aminoalkyl-substituted flavonoid derivatives 5a-5r were designed, synthesized and evaluated as potential cholinesterase inhibitors. The results showed that most of the synthesized compounds exhibited potent acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities at the micromolar range. Compound 2-(naphthalen-1-yl)-7-(8-(pyrrolidin-1-yl)octyloxy)-4H-chromen-4-one (5q) showed the best inhibitory activity (IC50, 0.64µM for AChE and 0.42µM for BChE) which were better than our previously reported compounds and the commercially available cholinergic agent Rivastigmine. The results from a Lineweaver-Burk plot indicated a mixed-type inhibition for compound 5q with AChE and BChE. Furthermore, molecular modeling study showed that 5q targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, these compounds (5a-5r) did not affect PC12 and HepG2 cell viability at the concentration of 10µM. Consequently, these flavonoid derivatives should be further investigated as multipotent agents for the treatment of Alzheimer's disease.

Spectral shifts and spectral switches of light generated by scattering of arbitrary coherent waves from a quasi-homogeneous media.

Within the accuracy of the Born approximation, it is shown that the light, which is generated by the scattering of an arbitrary coherent polychromatic wave from a quasi-homogeneous (QH) media can, display both spectral shifts and spectral switches. In our study, a pair of Young's pinholes is utilized to modulate spatial coherence of the incident plane wave before it interacts with the scatterer. The spectral shifts are found to be highly dependent of the scattering angle, the correlation length of scatterer and the Young's configuration parameter. Moreover, the spectral shifts can be converted from the red shift to blue one provided that the correlation length of scatterer is small enough. Derived results are confirmed by numerical simulations where influences of various factors on the spectrum are analyzed in detail.

Condition for invariant spectrum of an electromagnetic wave scattered from an anisotropic random media.

Within the accuracy of the first-order Born approximation, sufficient conditions are derived for the invariance of spectrum of an electromagnetic wave, which is generated by the scattering of an electromagnetic plane wave from an anisotropic random media. We show that the following restrictions on properties of incident fields and the anisotropic media must be simultaneously satisfied: 1) the elements of the dielectric susceptibility matrix of the media must obey the scaling law; 2) the spectral components of the incident field are proportional to each other; 3) the second moments of the elements of the dielectric susceptibility matrix of the media are inversely proportional to the frequency.

Near-field evanescent waves scattered from a spatially deterministic and anisotropic medium.

The scattering of light from an anisotropic medium, which may present either spatially random or deterministic statistics, has attracted substantial interest where the measurement of structural properties of scatterers is concerned. To date, however, no literature has studied near-zone evanescent waves scattered from a spatially deterministic and anisotropic medium. In this Letter, integral expressions are derived to represent electric fields of evanescent waves in the near-zone scattered field. In addition, the dependences of spectral densities of scattered field on the propagation distance of evanescent waves and effective radius of the scattering potential (ERSP) are also shown by numerical graphs, respectively. Potential applications of our study include the near-field optical microscopy and biomedical sensing.

Spectral shifts of evanescent waves generated by the scattering of polychromatic light in the near field.

Evanescent waves generated by the scattering of polychromatic light using a spatially deterministic medium and their near-zone spectral properties, to the best of our knowledge, have not been addressed in the literature. On the basis of the first-order Born approximation, we formulate expressions for the near-zone scattered wave by assuming that the scattering potential of the medium is of the Gaussian profile. The dependence of the spectral shift on effective sizes of the scattering potential (ESSP) is shown using numerical simulations. It is indicated that the increase of either ESSP or near-field diffraction length can induce spectral shifts in scattered evanescent waves.

A comparative first principles study on trivalent ion incorporated SSZ-13 zeolites.

The dispersion-corrected density functional theory has been used to study the trivalent ions B, Al, Ga, and Fe incorporated SSZ-13-type zeolites. The associated structure and Brønsted/Lewis acidity change caused by the incorporation ions were comparatively studied. It was found that the smaller the radius differences of the incorporation ions are, the smaller the changes in the structure will be and the less acidity will be enhanced for the Brønsted sites. The trivalent Al is found to be the most favorable trivalent incorporation ion and Na is found to be the most favorable charge balanced ion for the synthesis of SSZ-13-type zeolites due to size comparability, which are in line with the experimental observation. The substitution energies which show the relative synthesis difficulty level were also applied for B, Al, Ga, and Fe incorporated zeolites and found that the difficulty decreases with order of Fe > B > Ga ≫ Al, also in good agreement with the experimental observations. Adsorption studies for the NH3 and pyridine molecules indicate that adsorption on the Brønsted acid sites is more stable than on the Lewis acid sites. The Brønsted acidity was found to follow the order of HAl-SSZ-13 > HGa-SSZ-13 ≈ HFe-SSZ-13 > HB-SSZ-13 where the Lewis acidity was found to follow the order of HGa-SSZ-13 ≈ HFe-SSZ-13 > HAl-SSZ-13 > HB-SSZ-13. Our results provide new insights for the synthesis of the SSZ-13-type zeolites and fundamental information for the zeolitic catalyst designation to enhance the catalytic performance.

[Research on Collateral-unblocking Medicines for Cardiovascular Diseases under the Guidance of Vessels Collateral Theory].

OBJECTIVE: "Vessels Collateral Theory", as the inherit and development of "blood vessels" in Huangdi Neijing, is a systematic system by integrating severe vascular diseases. In this article, by taking cardiovascular diseases (CVD) as a cut-in point, roles of "minute collateral-microvascular" lesions in the occurrence and development of CVD were further explored. The interventional effect of collateral-unblocking medicines under the guidance of Vessels Collateral Theory was also in-depth explored, hoping to leading Chinese medical prevention and treatment of CVD.

Effects of drying process of yuanzhi (Radix Palygalae) on its bioactive ingredients.

OBJECTIVE: To study the effects of the drying processing in terms operational parameters on the bioactive constituents of six Yuanzhi (Radix Palygalae) samples across China. METHODS: Six Yuanzhi (Radix Palygalae) samples were investigated using thermogravimetry analysis. The heating courses were set in two ways: the temperature-programmed process from room temperature to 150 degrees C, and the constant-temperature course at 50 degrees C, 70 degrees C and 90 degrees C. RESULTS: The peak temperature of six Yuanzhi (Radix Palygalae) samples ranged from 78 degrees C to 88 degrees C. The mass loss rate of Yuanzhi (Radix Palygalae) alcohol-soluble extract was significantly increased when heated at 90 degrees C. Four types of bioactive ingredients were detected in volatile oils of Yuanzhi (Radix Palygalae) sample from Shanxi province by Gas Chromatography-mass spectrometry analysis. Fourier Transform Infrared Spectroscopy results showed that the drying temperature exerted a great influence on types and amount of ingredients of Yuanzhi (Radix Palygalae). The kinetic study showed that the constant-temperature drying process of Yuanzhi Radix Palygalae) samples could be well described by the Page Model, especially for the drying process at 50 degrees C, in which R2 and SD values were more than 0.98 and less than 0.04, respectively. The drying constant k of three Yuanzhi (Radix Palygalae) samples from Shanxi, Gansu and Shaanxi provinces in China was corresponding to the Arrhenius equation, and their activation energies were 28.07, 25.38 and 21.48 kJ/mol, respectively. CONCLUSION: The drying process of Yuanzhi (Radix Palygalae) was very important for bioactive ingredients improvement in Yuanzhi (Radix Palygalae). Temperature was a thermodynamic property significantly affecting the process.

Pd/activated carbon sorbents for mid-temperature capture of mercury from coal-derived fuel gas.

Higher concentrations of Hg can be emitted from coal pyrolysis or gasification than from coal combustion, especially elemental Hg. Highly efficient Hg removal technology from coal-derived fuel gas is thus of great importance. Based on the very excellent Hg removal ability of Pd and the high adsorption abilities of activated carbon (AC) for H2S and Hg, a series of Pd/AC sorbents was prepared by using pore volume impregnation, and their performance in capturing Hg and H2S from coal-derived fuel gas was investigated using a laboratory-scale fixed-bed reactor. The effects of loading amount, reaction temperature and reaction atmosphere on Hg removal from coal-derived fuel gas were studied. The sorbents were characterized by N2 adsorption, X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). The results indicated that the efficiency of Hg removal increased with the increasing of Pd loading amount, but the effective utilization rate of the active component Pd decreased significantly at the same time. High temperature had a negative influence on the Hg removal. The efficiency of Hg removal in the N2-H2S-H2-CO-Hg atmosphere (simulated coal gas) was higher than that in N2-H2S-Hg and N2-Hg atmospheres, which showed that H2 and CO, with their reducing capacity, could benefit promote the removal of Hg. The XPS results suggested that there were two different ways of capturing Hg over sorbents in N2-H2S-Hg and N2-Hg atmospheres.