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Chengcheng Sun,1 Meixia Liu,1 Jiangang Liu,2 Tingting Zhang,3 Lei Zhang,4 Hao Li,1 Zenggang Luo5 1Department of Geriatrics, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, People’s Republic of China; 2Department of Cardiovascular, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, People’s Republic of China; 3Department of Geriatrics, College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, ShanDong Province, People’s Republic of China; 4Department of Emergency, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, People’s Republic of China; 5Medical Administration Office, Beijing Administration of Traditional Chinese Medicine, Beijing, 100053, People’s Republic of ChinaCorrespondence: Meixia Liu; Jiangang Liu Email liumeixia2004@126.com; liujiangang2002@sina.comBackground: ShenmaYizhi decoction (SMYZD) is an effective prescription of traditional Chinese medicine used to treat vascular dementia (VD). Modern research methods have identified its active ingredients clearly as gastrodin, ferulic acid, ginsenosides, and β-sitosterol. Chronic cerebral hypoperfusion is a driving factor or risk factor for VD, which leads to the disturbance of mitochondrial structure and function.Purpose: To observe whether SMYZD improves cognitive impairment by improving mitochondrial structure and function.Methods: Forty adult rats with vascular cognitive impairment (VCI) caused by the bilateral ligation of common carotid arteries were divided into four groups randomly, including the model group, donepezil group, and low-dose and high-dose SMYZD groups, with 10 rats in each group. Additionally, a sham group was established with 10 rats as the control group. The treatment groups were administered donepezil and two different dosages of SMYZD. The donepezil group was administered 0.45 mg/kg/d donepezil, and the SMYZ-L group was administered 2.97 g/kg/d SMYZ, which were equivalent to the clinical dosage. The SMYZ-H group was administered 11.88 g/kg/d SMYZ, which is 4 times higher than the clinically equivalent dosage. A sham-operated group was used as the control group and administered an equal volume of distilled water. The rats were treated by gavage for 8 consecutive weeks. Morris water maze (MWM) test was performed to evaluate the learning and memory ability. The mitochondria of brain tissue were extracted from brain for further test. Mitochondrial morphology and the signal path of AMPK/PPARα/PGC-1α/UCP2 in mitochondria were detected.Results: With the SMYZD intervention, behavioral performance of rats and pathological changes of mitochondria of brain tissue were significantly improved. In the serum, SOD, GSH-Px, and GSH activities were increased, and the MDA content was decreased. Moreover, the AMPK, PPARα, PGC-1α, UCP2, and ATP5A mRNA and protein expression levels were also reversed by SMYZD.Conclusion: SMYZD may provide a potential therapeutic strategy via activating the AMPK/PPARα/PGC-1α/UCP2 signal pathway to improve mitochondrial structure and energy metabolism thereby alleviate vascular cognitive impairment.Keywords: vascular cognitive impairment, ShenmaYizhi decoction, mitochondria energy metabolism, bilateral common carotid artery occlusion

This study presents an effective high-speed countercurrent chromatography method of two-phase solvent system combined with ionic liquids for the isolation and purification of four major compounds of γ-oryzanol from rice bran oil. The conditions of high-speed countercurrent chromatography, including solvent systems and the content of ionic liquids, were optimized to improve separation efficiency. The optimal solvent system was n-hexane–dichloromethane–acetonitrile–[C4mim][PF6] at a volume ratio of (10:1:10:0.15, v/v). Adding a small amount of ionic liquids significantly improved the separation efficiency. Four compounds of γ-oryzanol, cycloartenyl ferulate, 24-methylene cycloartanyl ferulate, campesteryl ferulate, and sitosteryl ferulate were successfully purified in one run from rice bran oil with the purities of 95.25%, 92.48%, 92.47%, and 93.43%, respectively. The result of bioassay showed that rice bran oil and separated individual cycloartenyl ferulate could significantly inhibit mycelium growth of crop diseases Rhizoctonia solani and Fusarium graminerum, the bioactivity of cycloartenyl was higher than that of the rice bran oil. The cellular antioxidant activity experimental result indicted that cycloartenyl ferulate could alleviate H2O2-induced oxidative stress.

The volatile oil of Mentha haplocalyx is widely used in medicine, food, and cosmetics. However, a large amount of its residue after steam extraction of volatile oil is abandoned, resulting in a waste of resources. The method of aqueous two-phase flotation coupled with preparative high-performance liquid chromatography was established for the separation and purification of nonvolatile active compounds from Mentha haplocalyx for the first time. The parameters of the two-phase aqueous flotation were optimized. Under the optimal conditions including flotation solvent PEG 1000 aqueous solution (1:1, w/w), pH 5, (NH4 )2 SO4 concentration of 350 g/L in aqueous phase, N2 flow rate of 20 mL/min, and flotation time of 20 min, the flotation efficiency of linarin, hesperidin, and didymin was 82.24, 76.38, and 89.33%, respectively. The linarin and hesperidin with the high purities of 95.8 and 97.2%, respectively, were obtained by using preparative high performance liquid chromatography. The neuroprotective effect of linarin against H2 O2 -induced oxidative stress in rat hippocampal neurons was investigated. The experimental result indicated that linarin could alleviate H2 O2 -induced oxidative stress. The work indicated that the combination of aqueous two-phase flotation and preparative high performance liquid chromatography is a feasible and practical method for the purification of nonvolatile active substances from Mentha haplocalyx, which would provide a reference process for the comprehensive utilization of M. haplocalyx. Especially, linarin might be used as a good source of natural neuroprotectants.

In crystalline/crystalline polymer blend systems, complex competition and coupling of crystallization and morphology usually happen due to the different crystal nucleation and growth processes of polymers, making the morphology and crystallization behavior difficult to control. Herein, we probe the crystallization sequence during the film formation process (crystallize simultaneously, component A crystallizes prior to B or inverse) to illustrate the micro-morphology evolution process in poly(3-hexylthiophene) (P3HT) and poly[[N,N-bis(2-octyldodecyl)-napthalene-1,4,5,8-bis(dicarboximide)-2,6-diyl]- alt-5, 5'-(2,2'-bithiophene)] (N2200) blend using in situ UV-vis absorption spectra and in situ two-dimensional grazing incidence X-ray diffraction (2D GIXRD). When P3HT and N2200 crystallize simultaneously, a large-sized morphology structure is formed. When strengthening the solution aggregation of P3HT by increasing the solvent-polymer interaction, P3HT crystallizes prior to N2200. A P3HT-based micro-morphology structure is obtained. As the molecular weight of N2200 increases to a critical value (72.0 kDa), the crystallization of N2200 dominates the film formation process. A N2200-based micro-morphology is formed guided by N2200 domains. The results confirm that the crystallization sequence is one of the most important factors to determine the micro-morphology structure in all-crystalline polymer blends.

High-performance polymer donors are highly demanded to fulfil the potential of layer-by-layer (LBL) processed organic solar cells (OSCs). In this study, we present an effective method to develop high-performance polymer donors for LBL-OSCs by manipulating their solubility properties. The solubility of naphthalenothiophene imide (NTI)-based polymers could be easily manipulated by employing linear or branched alkyl chains in NTI. The polymer PNTB6-Cl with linear alkyl chains insoluble in chloroform could tolerate the chloroform processing by washing away the polymers only in the amorphous region, resulting in an LBL film with a much smoother surface and more efficient photoluminescence quenching, while chloroform-soluble polymer PNTB-Cl did not. PNTB6-Cl:N3 based LBL devices exhibited an efficiency of 17.59%, much higher than 15.24% for PNTB-Cl:N3 based devices and 16.20% for control devices based on PM6:N3. Importantly, the excellent batch-to-batch reproducibility of PNTB6-Cl overcomes the notorious batch-dependent issue in polymer donors, indicating that PNTB6-Cl is a promising polymer donor for LBL-OSCs. Our studies demonstrate that the solubility property of a polymer could significantly impact electron acceptor penetration, phase separation and photovoltaic performance of LBL-OSCs, which provide the guidelines for high-performance polymer donor design.

The morphology of active layer in bulk heterojunction (BHJ) organic solar cells is decisive to the device performance. Previous works have shown that the solvent engineering is an effective method to optimize the morphology of active layer. However, screening the proper solvent is a tedious task, and we know very little about how to select a proper solvent for a particular system, especially for polymer/non-fullerene blend systems. Here, we combined the spectroscopic analysis in various solvent mixtures during film-forming process to reveal the relationship among the cosolvent characteristics, film-forming kinetics and film morphology. In this article, P3HT/O-IDTBR blend was selected as model system due to being facile synthesized under a large-scale. Chlorobenzene (CB) was selected as main solvent, and the cosolvents were grouped into three categories according to its boiling point (bp) compared to CB. The cosolvents with lower bp, like chloroform (CF), can facilitate a faster film-forming process, reducing the domain size but sacrificing the crystallinity of both components. For the cosolvents with higher bp, like o-dichlorobenzene (DCB) and 1,2,4-trichlorobenzene (TCB), the self-organization process of P3HT and O-IDTBR is separated and its duration was extended, constructing highly crystalline nano-interpenetrating network. However, the cosolvents with very high bp, such as chlornaphthalene (CN), would residue in film and keep P3HT and O-IDTBR self-organizing for longer time, leading to larger phase separation. This work systematically investigated the effect of cosolvent on the film-forming kinetics, and proposed a guideline of how to select a proper cosolvent according to the crystallinity and domain size of active layer.

Background: Alzheimer’s disease (AD) and vascular dementia (VaD) are major types of dementia, both of which cause heavy economic burdens for families and society. However, no currently available medicines can control dementia progression. Rhizoma coptidis, a Chinese herbal medicine, has been used for >2000 years and is now gaining attention as a potential treatment for AD and VaD. Methods: We reviewed the mechanisms of the active ingredients of Rhizoma coptidis and Rhizoma coptidis-containing Chinese herbal compounds in the treatment of AD and VaD. We focused on studies on ameliorating the risk factors and the pathological changes of these diseases. Results: The Rhizoma coptidis active ingredients include berberine, palmatine, coptisine, epiberberine, jatrorrhizine and protopine. The most widely studied ingredient is berberine, which has extensive therapeutic effects on the risk factors and pathogenesis of dementia. It can control blood glucose and lipid levels, regulate blood pressure, ameliorate atherosclerosis, inhibit cholinesterase activity, Aβ generation, and tau hyperphosphorylation, decrease neuroinflammation and oxidative stress and alleviate cognitive impairment. Other ingredients (such as jatrorrhizine, coptisine, epiberberine and palmatine) also regulate blood lipids and blood pressure; however, there are relatively few studies on them. Rhizoma coptidis-containing Chinese herbal compounds like Huanglian-Jie-Du-Tang, Huanglian Wendan Decoction, Banxia Xiexin Decoction and Huannao Yicong Formula have anti-inflammatory and antioxidant stress activities, regulate insulin signaling, inhibit γ-secretase activity, neuronal apoptosis, tau hyperphosphorylation, and Aβ deposition, and promote neural stem cell differentiation, thereby improving cognitive function. Conclusion: The “One-Molecule, One-Target” paradigm has suffered heavy setbacks, but a “multitarget- directed ligands” strategy may be viable. Rhizoma coptidis active ingredients and Rhizoma coptidiscontaining Chinese herbal compounds have multi-aspect therapeutic effects on AD and VaD.

The research on advanced functional polymers is being driven by the fast-growing demand for new functional materials that can be used in revolutionary technologies. Polymers can be endowed with functions by using certain special preparation methods or by introducing functional groups or fillers into materials. These functions are either intrinsically possessed by materials or actuated by external stimuli. In this review, we present an overview of the recent developments made in the research hotspots of functional polymers, encompassing polymerization methodologies, luminescent polymers, photovoltaic polymers, other electronic and optical polymers (including low-k polyimides and second-order nonlinear optical polymers), biorelated polymers (particularly those for biomedical applications), supramolecular polymers, stimuli-responsive polymers, shape-memory polymers, separation polymer membranes, energy storage polymers, and covalent organic framework polymers. The concepts, design strategies at the molecular level, preparation methods, classifications, properties, potential applications, and recent progress made in such polymers are summarized. Challenges and future perspectives of each type of functional polymers are also addressed, including research efforts regarding the design and fabrication of functional polymers for serving the increasing demand for new materials.

We determined the antitumor mechanism of apatinib in glioma using a patient-derived orthotopic xenograft (PDOX) glioma mouse model and glioblastoma (GBM) cell lines. The PDOX mouse model was established using tumor tissues from two glioma patients via single-cell injections. Sixteen mice were successfully modeled and randomly divided into two equal groups (n = 8/group): apatinib and normal control. Survival analysis and in vivo imaging was performed to determine the effect of apatinib on glioma proliferation in vivo. Candidate genes in GBM cells that may be affected by apatinib treatment were screened using RNA-sequencing coupled with quantitative mass spectrometry, data mining of The Cancer Genome Atlas, and Chinese Glioma Genome Atlas databases, and immunohistochemistry analysis of clinical high-grade glioma pathology samples. Quantitative reverse transcription-polymerase chain reaction (qPCR), western blotting, and co-immunoprecipitation (co-IP) were performed to assess gene expression and the apatinib-mediated effect on glioma cell malignancy. Apatinib inhibited the proliferation and malignancy of glioma cells in vivo and in vitro. Thrombospondin 1 (THBS1) was identified as a potential target of apatinib that lead to inhibited glioma cell proliferation. Apatinib-mediated THBS1 downregulation in glioma cells was confirmed by qPCR and western blotting. Co-IP and mass spectrometry analysis revealed that THBS1 could interact with myosin heavy chain 9 (MYH9) in glioma cells. Simultaneous THBS1 overexpression and MYH9 knockdown suppressed glioma cell invasion and migration. These data suggest that apatinib targets THBS1 in glioma cells, potentially via MYH9, to inhibit glioma cell malignancy and may provide novel targets for glioma therapy.

Potato (Solanum tuberosum L.) is the third food crop in the world. China is the biggest potato producer worldwide where 60% of the potato crop is cultivated in arid and semi-arid climates. Only a few varieties with high drought tolerance were released in China. It is important to accelerate the selection of drought resistant cultivars in a fast, simple and efficient method. Ten advanced clones, which were selected based on the results from two-years drought evaluation trials, along with two widely-adopted cultivars in China with contrast-drought resistance were evaluated under well-watered condition and water restriction condition. Plant traits related to gas exchange, chlorophyll, specific leaf area (SLA) and leaf dry matter content (LDM) were collected at 0, 20, 40 and 60 days after water restriction. Moreover, tuber number and tuber yield were measured at harvest. Tuber number and weight were reduced by drought. The drought index (DI) of the pot trial had a strong correlation with that of the field trial. Net photosynthesis and stomatal conductance were related to yield in the early stages. SLA and LDM had significantly positive and negative correlations respectively with DI after water restriction. Genotype C93 had the highest DI and yield stability followed by C112, C46 and C82 in the pot trial. All had better performance than the best local variety “Tacna”. Our findings suggested that the four clones above can be good candidates for drought tolerance breeding. SLA and LDM could be the low-cost and efficiency indicators for potato drought resistance selection after tuber initiation.

The intermixed phase is important in effective charge separation due to the formation of cascaded energy landscape between intermixed phase and pure phases in polymer/fullerene solar cells. However, the quantitative relationship between the charge separation and the content of intermixed phase has not been investigated clearly so far. Here, we proposed to tune the content of the polymer/PC71BM intermixed phase by changing the polymer solution conformation. Poly[2,5-bis(3-tetradecylthiophen-2-yl)thieno[3,2-b]thiophene] (PBTTT) and PC71BM was selected as a model system. The organization of the PBTTT in solution promotes the formation of ordered aggregates as aging time increases, the interdigitation of side-chains restricts the intercalation of PC71BM. Therefore, the intermixed phase formed by intercalation PC71BM to PBTTT side chain can be controlled. When the aging time increasing from 0 to 80 min, the extent of intercalation gradually from almost complete intercalated phase to almost non-intercalated. As the content of intercalated phase is about 11%, the charge dissociation is most efficient and short circuit current (Jsc) increased from 1.60 mA/cm2 to 4.94 mA/cm2, leading to optimized device performance.

For poly(9,9-dioctylfuorene) (PFO), β phase (coplanar conformation with the intra-chain torsion angle of 165°) has a greater conjugation length and higher degree of order compared to those of α phase, which favors charge carrier transport. However, the highest content of β phase obtained so far is 45%. We propose to increase the content of β phase by promoting the solution aggregation of PFO molecules and extending film-forming time. For this purpose, 1,8-diiodooctane (DIO) is added to PFO o-xylene solution, which enhances the interaction of PFO chains and improves the planarity of PFO backbone, resulting in the formation of ordered aggregation. The aggregates act as nucleation centers to promote the formation of β phase. The content of β phase increases with increasing DIO concentration and reaches a platform of 39% as DIO is more than 4 vol%. Furthermore, the film is kept in a sealed environment with o-xylene atmosphere for 3 h, thus the PFO molecules have enough time to diffuse to the crystallization front and achieve disorder-order transition. As a result, the crystallinity of PFO is improved significantly and the content of β phase increases to 52%, reaching the highest value reported so far.

Myocardial fibrosis is implicated as a leading risk factor for heart failure, arrhythmia, and sudden death after cardiac injury, as the excessive interstitial extracellular matrix impedes heart contraction and electrical conduction. Complicated mechanisms involving oxidative stress, pro-inflammatory cytokines, chemokine families, NLRP3 inflammasomes, growth factors, and non-coding RNAs participate in cardiac fibrogenesis and make it difficult to designate specific and effective therapies. Oriental herbs have been popular for thousands of years in the health care of Asian residents, due to their multi-targeted, multi-faceted approaches and their multi-functional effects in fighting difficult and complicated diseases, including cardiovascular disorders such as myocardial fibrosis. Curcumin, a natural polyphenol and yellow pigment obtained from the spice turmeric, was found to have strong anti-oxidant and anti-inflammatory properties. Increasing evidence has shown that curcumin can be used to prevent and treat myocardial fibrosis, when the myocardium suffers pathological pro-fibrotic changes in vivo and in vitro. The present review focuses on recent studies elucidating the mechanisms of curcumin in treating different pathologic conditions, including ischemia, hypoxia/reoxygenation, pressure or volume overload, and hyperglycemia or high-fat-induced cardiac fibrosis. Novel analogs such as C66, B2BrBC, Y20, and J17 have been designed to maximize the therapeutic potentials of curcumin. These optimized curcumin analogs with improved bioavailability and pharmacokinetic profiles need to be clinically verified before curcumin could be recommended for the treatment of myocardial fibrosis.

Parkinson's disease is the second most common neurodegenerative disease. Researchers have shown that oxidative stress and apoptosis play an important role in the Parkinson's disease process. Isoquercitrin (quercetin-3-O-β-d-glucopyranoside) is a natural flavonol compound and one of the main active ingredients of agricultural waste apple pomace. Increasing evidence indicates that this compound possesses anti-oxidation, anti-aging, and anti-inflammation properties. In this study, isoquercitrin was purified from apple pomace by high-speed countercurrent chromatography and its neuroprotective effect on Parkinson's disease was investigated in MPTP-induced acute mouse models. It was found that isoquercitrin ameliorated the animal behaviors against MPTP-induced neurotoxicity, mitigated the loss of dopamine neurons induced by MPTP, increased tyrosine hydroxylase and dopamine transporter expression, reduced the pro-apoptotic signaling molecule bax expression and inhibited MPTP-triggered oxidative stress. Our results demonstrated that isoquercitrin has protective effects on the MPTP subacute model mouse, which might be partially mediated through the actions of anti-oxidation and anti-apoptosis. Isoquercitrin might be a new promising protective drug for the improvement of Parkinson's disease.

The development of glioblastoma (GBM) is typically accompanied by marked changes in lipid metabolism. Oxylipins and their catalyzed enzymes lipoxygenases (LOXs) have been shown to participate in the development of cancers via multiple pathways, while the understanding of LOXs in GBM remains enigmatic. Thus, we aimed to explore the expression and functional roles of LOXs in the development of GBM. Here we showed that ALOXE3 was markedly down-regulated in human GBM. Knockdown of ALOXE3 in GBM cells fostered the orthotopic tumor growth and shortened lifespan in mice. ALOXE3 deficiency rendered GBM cells resistant to p53-SLC7A11 dependent ferroptosis, promoting GBM cell survival. Mechanistically, miR-18a directly targeted ALOXE3 and suppressed its expression and functions in GBM cells. Furthermore, ALOXE3 silencing promoted 12-hydroxyeicosatetraenoic acids (12-HETE) secretion from GBM cells, in turn, 12-HETE enhanced migration of GBM cells by activating Gs-protein-coupled receptor (GsPCR)-PI3K-Akt pathway in an autocrine manner. Altogether, miR-18a/ALOXE3 axis exerts tumor promoting functions by regulating ferroptosis and migration of GBM cells. Targeting miR-18a/ALOXE3 axis may provide novel therapeutic approaches for GBM treatment.

The surface of Bacillus megaterium was modified by coating sodium alginate. The modified B. megaterium before and after adsorption were characterized by SEM, FTIR and XPS. The effects of pH, reaction time, initial U(VI) concentration and adsorbent dosage on the adsorption of U(VI) by the modified B. megaterium were studied by batch adsorption experiments. The adsorption process was studied by pseudo-first-order kinetics and pseudo-second-order kinetic models, Langmuir and Freundlich isotherms. The results showed that the maximum adsorption capacity of U(VI) was 74.61 mg g −1 under the conditions of pH 5.0, adsorbent 0.2 g l −1 , 30°C and initial U(VI) concentration of 15 mg l −1 . The adsorption process accords with pseudo-first-order kinetics and Langmuir isotherm. The adsorption capacity of U(VI) by the modified B. megaterium was still higher than 80% after five times of desorption and reuse experiments. In conclusion, the sodium alginate modified B. megaterium was an ideal material for U(VI) biosorption.

Recurrent high-grade glioma, a malignant tumor of the brain or spinal cord associated with poor prognosis with a median survival of6 months. Recurrent high-grade glioma does not have standard treatment even if some strategies have some effect in recurrent gliomas. Apatinib, as a tyrosine kinase inhibitor shown to be effective in treating the lung and gastric cancer. The present study investigated the efficacy and safety of apatinib in combination with dose-dense regimens of temozolomide for treating recurrent glioma.Eighteen patients with recurrent high-grade glioma were enrolled and treated with apatinib (500 mg/day) and TMZ (50 mg/mFrom the 18 cases, only 17 were included in the evaluation of the curative effect of the drug and in that four showed partial responses, ten had stable disease, remaining three exhibited progressive disease. The disease control rate was 82.3% (14/17). Progression-free and overall survival was found to be 4 months and 9.1 months, respectively. Three patients became transiently capable of self-care (Karnofsky performance status70). Cognition and quality of life improved after treatment and from the safety perspective, three most common adverse reactions included epilepsy (24.1%), hypertension (20.7%), and fatigue (17.2%).Apatinib and TMZ may represent an alternative treatment option for patients with recurrent high-gradeglioma, especially those with a low Karnofsky performance status. However, studies using a larger sample size are required to confirm these findings.

Reliable monitoring of metabolites in biofluids is critical for diagnosis, treatment, and long‐term management of various diseases. Although widely used, existing enzymatic metabolite assays face challenges in clinical practice primarily due to the susceptibility of enzyme activity to external conditions and the low sensitivity of sensing strategies. Inspired by the micro/nanoscale confined catalytic environment in living cells, the coencapsulation of oxidoreductase and metal nanoparticles within the nanopores of macroporous silica foams to fabricate all‐in‐one bio‐nanoreactors is reported herein for use in surface‐enhanced Raman scattering (SERS)‐based metabolic assays. The enhancement of catalytical activity and stability of enzyme against high temperatures, long‐time storage or proteolytic agents are demonstrated. The nanoreactors recognize and catalyze oxidation of the metabolite, and provide ratiometric SERS response in the presence of the enzymatic by‐product H2O2, enabling sensitive metabolite quantification in a “sample in and answer out” manner. The nanoreactor makes any oxidoreductase‐responsible metabolite a candidate for quantitative SERS sensing, as shown for glucose and lactate. Glucose levels of patients with bacterial infection are accurately analyzed with only 20 µL of cerebrospinal fluids, indicating the potential application of the nanoreactor in vitro clinical testing., Inspired by the spatially confined micro‐/nano‐environment in living cells, a plasmonic bio‐nanoreactor is developed by the coencapsulation of enzyme and surface‐enhanced Raman scattering tags within macroporous silica foams. The nanoreactor shows enhanced biocatalytic activity and stability, and thus the capability of molecular recognition and detection provides an all‐in‐one optical biosensor for reliable in vitro metabolic testing.

Purpose This study was designed to explore the underlying mechanism of action for a Fuzheng Quxie Decoction (FQD) in Alzheimer's disease (AD), to validate its neuroprotective effects, and to provide experimental support for its predicted mechanism of action. Methods An integrative approach to network pharmacology was performed to predict the mechanism of action for treatment of AD with FQD. The predicted mechanism was validated in SAMP8 mice. Results With predicted putative FQD targets and a collection of AD-related genes, 245 possible regulatory targets of FQD were identified for the treatment of AD. Pathway-enrichment analysis for the possible regulatory targets indicated that vascular endothelial growth factor (VEGF) and VEGF-receptor signaling were pivotal in the treatment of AD with FQD. In vivo experiments confirmed the neuroprotective effect and the predicted mechanism of action for treatment of AD with FQD. Conclusion This study contributes to an understanding of the neuroprotective effect of FQD and its potential mechanism of action for the treatment of AD.

The morphology of perovskite film plays a key role in determining photoabsorption, carrier transport and ambient stability in perovskite solar cells. However, due to the fast crystallization kinetics, the perovskite film fabricated by solution-processing technique usually suffers from low crystallinity and poor orientation. Here, both the morphology and the ambient stability of perovskite films were improved through regulating crystallization rate and enhancing intermolecular interaction by adding α, ω-diamino poly (ethylene glycol) (PEG-NH2) into precursor solution (mixture of CH3NH3I and PbCl2). The PEG-NH2 and Pb2+ tended to form a new chelated compound Pb2+-PEG-NH2. The stable multidentate chelation between Pb2+ and PEG-NH2 retarded the crystal growth rate to half of the one of the film without PEG-NH2, which is determined by the in situ UV–vis absorption spectra and in situ two-dimensional detection capability. The slow crystallization process is beneficial for realizing an uniform perovskite film with enhanced crystallinity almost 3 times of the pristine film, and increased crystal size from smaller than 100 nm to larger than 300 nm. In addition, the content of perovskite crystals adopted (h 0 0) orientation increased from 9.59% to 20.70% due to the flexible PEG-NH2 chains. Moreover, the ambient stability of perovskite films was also enhanced because the Pb-halogen bond in perovskite crystals became stronger as well as the film became defect-free. As a result, the device fabricated with PEG-NH2 attained a high efficiency of 15.6% with remarkably prolonged ambient stability without encapsulation. This work demonstrates that introducing the polymer that can coordinate to Pb2+ is a feasible way to simultaneously enhance both efficiency and stability of perovskite solar cells.

Autophagy begins with the nucleation of phagophores, which then expand to give rise to the double-membrane autophagosomes. Autophagosomes ultimately fuse with lysosomes, where the cytosolic cargoes are degraded. Accumulation of autophagosomes is a hallmark of autophagy and neurodegenerative disorders including Alzheimer’s and Huntington’s disease. In recent years, the sources of autophagosome membrane have attracted a great deal of interests, even so, the membrane donors for autophagosomes are still under debate. In this review, we describe the probable sources of autophagosome membrane.

Reliable profiling of the extracellular dopamine (DA) concentration in the central nervous system is essential for a deep understanding of its biological and pathological functions. However, quantitative determination of this neurotransmitter remains a challenge because of the extremely low concentration of DA in the cerebrospinal fluid (CSF) of patients. Herein, on the basis of the specific recognition of boronate toward diol and N-hydroxysuccinimide ester toward the amine group, a simple and highly sensitive strategy was presented for DA detection by using surface-enhanced Raman scattering (SERS) spectroscopy as a signal readout. This was realized by first immobilizing 3,3'-dithiodipropionic acid di( N-hydroxysuccinimide ester) on gold thin film surfaces to capture DA, followed by introducing 3-mercaptophenylboronic acid (3-MPBA)-functionalized silver nanoparticles to generate numerous plasmonic "hot spots" with the nanoparticle-on-mirror geometry. Such a dual-recognition mechanism not only avoids complicated bioelement-based manipulations but also efficiently decreases the background signal. With the direct use of the recognition probe 3-MPBA as a Raman reporter, the "signal-on" SERS method was employed to quantify the concentration of DA from 1 pM to 1 μM with a detection limit of 0.3 pM. Moreover, our dual-recognition-directed SERS assay exhibited a high resistance to cerebral interference and was successfully applied to monitoring of DA in CSF samples of patients.

Understanding the nucleation process is very important in growing polymer nanowires as it plays a decisive role in determining the crystal structure and size distribution. Polymer chain conformation determines whether the polymer chains could assemble to nuclei or not. Here, chain conformation and the nucleation process were controlled to grow 3,6-bis-(thiophen-2-yl)-N,N′-bis(2-decyl-1-tetradecyl)-1,4-dioxo-pyrrolo[3,4-c]pyrrole and thieno[3,2-b]thiophene (DT-PDBT-TT) nanowires. We changed the conformation of DT-PDBT-TT in solution and controlled the nucleation process by using a main solvent:cosolvent system. The main solvent was a low boiling point good solvent, and the cosolvent was consisted of two high boiling point solvents with different solubility. In fact, the chain conformation in the pristine solution was changed by choosing different main solvents (with H-bond, π–π or none interaction with the main chain) and temperatures. The absorption spectrum and TEM images showed that trichloro ethylene (TCE) was the best main solvent because it has H-bond interaction with the polymer main chain and DT-PDBT-TT conformation in it approaching unimer coil conformation, which is beneficial to grow nanowires. Mixed o-dichlorobenzene (ODCB) and anisole (AS) with different ratios were used to changing the solubility step by step to control nucleation process. Only when marginal cosolvent (ODCB:AS = 1:1) was added, could it decrease the nuclei number and avoided the aggregates simultaneously. As the main solvent evaporated slowly, the nucleation and growth happened, leading to the nanowires formation. The resulting nanowires were about 63 nm in width and one to two microns in length. The width of the DT-PDBT-TT structures suggests that the polymer chains are oriented along the fibril axis. Our results indicated that there are two requirements for the nanowire formation, (1) the polymer chain conformation should approach unimer coil; (2) the nucleation density should be optimized, not too much and no aggregation happened. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2018

A number of miRNAs have been found to be abnormally expressed or mutated in numerous cancers and thus, are considered to act as oncogenes or tumor suppressor genes. The aim of the present study was to investigate the effect of miR-181 on cisplatin-resistant non-small cell lung cancer (NSCLC). In patients with cisplatin-resistant NSCLC, miR-181 expression was found to be markedly decreased. In addition, in the cisplatin-resistant human lung adenocarcinoma cell line A549/DDP, miR-181 downregulation promoted cell growth and metastasis and inhibited cell apoptosis, whereas miR-181 overexpression exerted the opposite effects. Furthermore, miR-181 downregulation suppressed LC3 and ATG5 protein expression in A549/DDP cells through suppression of the PTEN/PI3K/AKT/mTOR pathway, whereas miR-181 overexpression recovered LC3 and ATG5 protein expression by promoting PTEN/PI3K/AKT/mTOR signaling. In turn, PTEN inhibitors reduced the anticancer effects of miR-181 overexpression on A549/DDP cell growth via the regulation of autophagy through the PI3K/AKT/mTOR pathway. Therefore, miR-181 may be a novel and important regulator of cisplatin-resistant NSCLC by serving a role in the regulation of apoptosis, as an established rate-limiting miRNA target.

The phase separation structure evolution process, i.e. confinement and broke out phenomenon in crystallization/crystallization poly (3-hexylthiophene) (P3HT) and poly [[N,N-bis(2-octyldodecyl)-napthalene-1,4,5,8-bis(dicarboximide)-2,6-diyl]- alt-5, 5′-(2,2′-bithiophene)] (N2200) blends were controlled by the polymer solution aggregation behavior and relative crystallization degree of each component. In this study, two different molecular weight of P3HT, Mw = 6 kDa and Mw = 55 kDa were selected and blend with N2200 as the model systems. Different molecular weight of P3HT had different crystalline ability in blend films. A similar phase separation of both two polymer blends could form in good solvent chloroform (CF). Marginal solvents and thermal annealing were employed to change the polymer solution aggregation behavior and relative crystallization degree of the two components. On one hand, when p-xylene (pX) was added as the co-solvent to increase the aggregation of P3HT molecules, for P3HT (Mw = 6 kDa)/N2200, the P3HT phase broke the restriction of N2200 phase while there was almost unchanged in P3HT (Mw = 55 kDa)/N2200. On the other hand, during thermal annealing, the P3HT molecule had a stronger molecular moving ability in P3HT (Mw = 6 kDa)/N2200 than that in P3HT (Mw = 55 kDa)/N2200 (the relative crystallization degree of these two polymers in P3HT (Mw = 6 kDa)/N2200 and P3HT (Mw = 55 kDa)/N2200 are 142 and 3, respectively). The pristine phase separation of P3HT (Mw = 6 kDa)/N2200 was destroyed effectively due to the unmatched crystallization degree of the two components and large sized fibrous phase separation was formed during thermal annealing. However, the pristine phase separation was almost unchanged in P3HT (Mw = 55 kDa)/N2200, and the P3HT molecule could partly ordered arrangement, which probably come from the almost matched crystallization degree of these two polymers. The results indicate that it is the Gibbs free energy that controls the phase separation in different relative crystallization degree. And different chain entanglements behavior was likely to be the main source of the morphological stability.

The ordered aggregation of non-fullerene small molecular acceptors (SMAs) plays a key role in determining the charge transport and bimolecular recombination in polymer/SMA solar cells. However, due to the competition between crystallization and phase separation, the polymers are prone to form a network first, which inhibits the molecular diffusion of SMAs, resulting in weak crystallinity of SMAs. Here, we demonstrated a sequential crystallization method for high performance PBDB-T/ITIC solar cells with much improved crystallinity of ITIC. By tuning the sequence of thermal annealing (TA) and solvent vapor annealing (SVA), sequential crystallization of ITIC and PBDB-T can be fine controlled to grow a highly crystalline ITIC and PBDB-T network. The crystallization kinetics results indicate that when the crystallization of ITIC occurred prior to the formation of the PBDB-T crystallized network, the crystallinity of ITIC is significantly improved due to high molecular diffusion. However, if the crystallization of PBDB-T occurred first, the diffusion of ITIC was restricted by the crystalline network of PBDB-T, resulting in a low crystallinity of ITIC. The enhanced crystallinity of ITIC is beneficial to the electron transport and suppressed the bimolecular recombination, which helps boost the device performance from 8.14% to 10.95%. This work demonstrates that manipulation of the crystallization sequence of the donor and acceptor may be key to further boost the efficiency of polymer/SMA solar cells.

Long coherence lengths (CLs) of crystals and proper intermixed phase amount guarantee charge transport and exciton dissociate efficiently, which is crucial for organic solar cells (OSCs) to achieve high device performance. However, extending CLs usually reduces the intermixed phase, leading to an insufficient interface for exciton dissociation. Herein, a strategy using a binary polymer with different molecular weights as donor is employed, that is, poly(3-hexylthiophene-2,5-diyl) (P3HT) with high (P3HT-H) and low (P3HT-L) molecular weight are blended as donor, and (5Z,5'Z)-5,5'-(((4,4,9,9-tetraoctyl-4,9-dihydro-s-indaceno[1,2-b:5,6-b']dithiophene-2,7-diyl)bis(benzo[c][1,2,5]thiadiazole-7,4-diyl))bis(methanylylidene))bis(3-ethyl-2-thioxothiazolidin-4-one) (O-IDTBR) is used as acceptor. In kinetics, the entanglements of P3HT-H are relieved due to the higher molecular diffusivity of P3HT-L. In thermodynamics, the miscibility of P3HT-L/O-IDTBR, P3HT-H/O-IDTBR, and P3HT-L/P3HT-H blends increases in turn. Hence, P3HT forms a more ordered structure with longer CLs after adding P3HT-L, which also drives O-IDTBR dispersed in P3HT crystalline regions diffuse to the O-IDTBR crystalline regions to further self-organize. Consequently, the CLs of both P3HT and O-IDTBR are extended, while keeping the intermixed phase amount proper. The optimized microstructure boosts device performance from 7.03% to 7.80%, which is one of the highest values reported for P3HT/O-IDTBR blends. This is a novel way to solve the conflict mentioned above, which may provide guidance to finely regulating the morphology of the active layer.

Flexible electronic devices have attracted considerable attention in recent years. Textile fabrics have been widely used to fabricate flexible strain sensors owing to their high flexibility. However, the elasticity of ordinary textile fabrics is low, which limits their strain sensing range. In this article, we used a simple method to fabricate flexible strain sensing fabrics (FSSFs) through the coating of graphene oxide (GO) nanosheets on elastic nylon/polyurethane (nylon/PU) fabric, followed by reduction of GO with sodium borohydride. The reduced graphene oxide (RGO) nanosheets were adsorbed on the elastic fabrics to impart electrical conductivity to the fabrics. The coated fabrics were characterized with scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and Raman scattering spectroscopy. The electromechanical performance and strain sensing properties of the FSSF were investigated. The fabricated strain sensor exhibited high sensitivity, a large workable strain range (0–30%), fast response and great stability. The mechanical property of fabrics did not change remarkably after the treatment with RGO. The surface resistance of the RGO/nylon/PU only increased from ∼112 KΩ/m 2 to ∼154 KΩ/m 2 after 8 washing cycles, exhibiting good washability. Furthermore, real-time monitoring of human motions, such as bending of finger and rotation of wrist, was achieved by the as-prepared FSSF. The RGO/nylon/PU fabrics as flexible strain sensors have potential applications in wearable electronic devices.

The macroscopic alignment of conjugated polymers with low grain boundary is essential to carrier transport. During film forming process, the match between contact line receding velocity and the critical alignment velocity is essential to get the alignment polymer film. In this paper, the contact line receding velocity of a D-A conjugated polymer film, isoindigo and bithiophene (IIDDT-C3), was adjusted by solvent vapor content and film-formation temperature. Only when solvent vapor content was 0.3 mL and the film-formation temperature was 90 °C, the contact line receding velocity was in accordance with the critical alignment velocity, and the highest degree of alignment was attained in the IIDDT-C3 film, with the dichroic ratio up to 4.08. Fibers were aligned parallel with the direction of the contact line receding and the molecules of IIDDT-C3 adopted an edge-on orientation with the backbone parallel with the direction of fiber long axis. The π - π stacking distance between adjacent molecules was 3.63 A.

The preparation of diketopyrrolopyrrole-based polymer nanowires seems very difficult, probably due to the fact that the nanowires length direction is along the main chain not the π-π direction. For the nanowires whose length direction is along the main chain, the probability of the short nanowires to meet the ends of other molecules to grow longer is very small. Herein, we prepared long 3,6-bis-(thiophen-2-yl)-N,N’-bis(2-octyl-1-dodecyl)-1,4-dioxo-pyrrolo [3,4- c ]pyrrole and thieno [3,2- b ]thiophene (PDBT-TT) nanowires followed a homogeneous nucleation and growth process by slowing the aggregate speed of the PDBT-TT molecules. Slowing the aggregate speed of the molecules was carried out by slow evaporation of the main solvent (the mixed solvent, consisting of a good solvent chloroform (CF) as the main solvent and a marginal solvent 1,2-dichlorobenzene (ODCB) as the co-solvent). CF evaporating at a speed of 30 μL/h allows the solution to be always in the saturated state and the polymer to aggregate slowly. The resulting nanowires are about 75 nm in width and tens of micrometers in length. The density and length of nanowires could be controlled by adjusting the concentration of the pristine solution and the evaporation process, respectively. Higher concentration of the pristine solution results in higher density of nanowires, and the length of nanowires also changed.

Objective To observe the effects of Huannao Yicong Formula (还脑益聪方, HYF) on learning and memory and it’s regulating effect on γ-secretase related anterior pharynx defective 1 (APH-1), presenilin enhancer-2 (PEN-2) signaling pathway, so as to discuss and further clarify the mechanism of HYF on Alzheimer’s disease.

An interpenetrating bulk-heterojunction structure with a domain size of 10–20 nm is the ideal morphology for carrier generation, separation and transportation in organic solar cells. However, depending on the blend composition, the phase-separation behavior of the crystalline small molecule blend system of donor 7,7′-(4,4-bis(2-ethylhexyl)-4H-silolo[3,2-b:4,5-b′]dithiophene-2,6-diyl)bis(6-fluoro-4-(5′-hexyl-[2,2′-bithiophen]-5-yl)benzo[c][1,2,5]thiadiazole) (p-DTS(FBTTh2)2) and acceptor N,N′-bis(1-ethylpropyl)-perylene-3,4,9,10-tetracarboxylic diimide (EP-PDI) is quite different. When the weight ratio of p-DTS(FBTTh2)2/EP-PDI is greater than 8 : 2 or smaller than 4 : 6, a large phase separation structure is observed induced by p-DTS(FBTTh2)2 or EP-PDI crystallization. When the ratio of p-DTS(FBTTh2)2 : EP-PDI changes from 7 : 3 to 5 : 5, no obvious phase separation can be detected due to the interaction between p-DTS(FBTTh2)2 and EP-PDI. In order to obtain the interpenetrating bulk-heterojunction structure with a domain size of 10–20 nm, we proposed to tune the molecule diffusion of p-DTS(FBTTh2)2 and EP-PDI by different thermal annealing temperature to control the phase separation domain size and phase purity. When the annealing temperature is T Tc p-DTS(FBTTh2)2 − Tb (T is the thermal annealing temperature, Ta and Tb are constants), the molecule diffusion rate of both p-DTS(FBTTh2)2 and EP-PDI is too slow or too fast, resulting in no phase separation or large phase separation morphology. When T is between Tm EP-PDI + Ta and Tc p-DTS(FBTTh2)2 − Tb, EP-PDI is in a melting state, but p-DTS(FBTTh2)2 self-assembles into crystals. As a result, p-DTS(FBTTh2)2 crystallized and formed a framework, which inhibited the massive crystallization of EP-PDI due to the spatial confinement of the p-DTS(FBTTh2)2 crystallization framework, leading to the formation of a bi-continuous phase separation structure with suitable domain size and phase purity. Based on the above phase separation structure we got, a power conversion efficiency of 4.25% was obtained, which is relatively high in this system without any additives.

Nanoscale interpenetrating networks play a key role in determining the optoelectrical properties of functional blends. However, phase separated large domain sizes could probably be observed in pristine films composed of two crystalline components. For example, p-DTS(FBTTh2)2/P(NDI2OD-T2) 3/2 blend films with interpenetrating networks are obtained, however, large domain sizes are found when they are prepared from a 20 °C solution due to the simultaneous process of crystallization and phase separation during solvent evaporation. In this paper, we proposed to reduce the domain size of p-DTS(FBTTh2)2/P(NDI2OD-T2) blend films using their different solution aggregation behaviors at different temperatures. The aggregation of p-DTS(FBTTh2)2 molecules in chlorobenzene (CB) was insensitive to the solution temperature. However, the in situ absorption spectra of the neat P(NDI2OD-T2) solution from 80 °C to room temperature indicated that P(NDI2OD-T2) aggregation increased with decreasing temperature due to intrachain interactions. Therefore, in order to reduce the domain size, we employed a hot solution to prepare the blend films. During the solidification process, the majority of p-DTS(FBTTh2)2 molecules were confined in the P(NDI2OD-T2) networks prior to occurrence of severe p-DTS(FBTTh2)2 aggregation. Thus, the domain size of the p-DTS(FBTTh2)2 phase became smaller than that of the pristine films, leading to a decrease in the corresponding photoluminescence intensity of the blend films. In addition, the crystallinity of the blend films improved after thermal annealing, which resulted from the ordered alignment of p-DTS(FBTTh2)2 molecules facilitated by their enhanced diffusion ability. Based on the various morphologies, a possible phase diagram of the p-DTS(FBTTh2)2/P(NDI2OD-T2) blend system was depicted, which could be a guide to directly control the morphology of blend films.

The macroscopic alignment of conjugated polymers with few grain boundaries is essential for carrier transport. It is well known that molecular conformation has a big role in achieving macroscopic alignment. Therefore, in this paper, a series of isoindigo-based conjugated polymers, the copolymer of isoindigo and thieno-[3,2-b]thiophene (IID–TT), isoindigo and bithiophene (IIDDT) and isoindigo and benzodithiophene (IID–BDT), were chosen to investigate the effect of molecular conformation on the fiber alignment. The long-range ordered film was obtained for IID–TT by drop-casting and solvent vapor enhanced drop-casting (SVE DC). The dichroic ratio (DR) of the IID–TT film obtained by SVE DC was 2.08 higher than that of the other two isoindigo-based conjugated polymers (IIDDT and IID–BDT), 1.07 and 1.33, respectively. The fibrils in the IID–TT film obtained by SVE DC were parallel and grown along the molecular backbones, but the fibrils of IIDDT and IID–BDT were both isotropic. The torsion angle of IID–TT (isoindigo and thieno-[3,2-b]thiophene) is 1.22°, while the torsion angle of IIDDT (isoindigo and thiophene, thiophene and thiophene) is 0.97° and 0.38° and that of IID–BDT (isoindigo and benzodithiophene) is 1.32°, respectively. The molecular conformation of IID–TT is the most coplanar among the three copolymers. The alkyl-stacking distance of IID–TT was 20.96 A larger than that of IIDDT (19.25 A) and IID–BDT (19.75 A) which indicated that the interaction of the side-chain of IID–TT was the weakest among the three conjugated polymers. The DR increased with the increase in the alkyl-stacking distance. The weak interaction of the side-chain in IID–TT was beneficial for the rearrangement of molecules in parallel. The coplanar conformation could accelerate interchain assembly of the parallel molecules through π–π interaction to form parallel fibers.

Broadening the absorption spectrum and efficiently harvesting photogenerated excitons are crucial tasks to realize high-efficiency polymer solar cells (PSCs). Recently, ternary PSCs with complementary absorptions into a single junction device have been emerging as a promising strategy to enhance the absorption of binary PSCs. However, the effect of ternary PSCs critically depends on the location of the third component according to different principles. Due to the hard control of the third component location, only limited high-performance ternary systems have been demonstrated previously. Here, we develop a new concept of dual Forster resonance energy transfer (dual-FRET), in which the third component acts as an “energy donor” and the donor and acceptor act as an “energy acceptor”. Thus, exciton energy of the third component could transfer energy to both the donor and the acceptor through the FRET principle. Consequently, the third component should only be dispersed uniformly in the binary film regardless of its location. Using this concept, the performance of ternary PSCs, i.e., PTB7-Th (donor)/P(NDI2OD-T2) (accepter)/PF12TBT (the third component), reaches 6.07%, more than about 30% compared to the corresponding binary PSCs (4.70%). Our work provides a novel way for designing ternary structures to boost the efficiency of PSCs.

The current understanding of the active layer morphology in ternary organic solar cells (OSCs) is superficial owing to more variables and complexity compared to that of binary OSCs. The PTB7-Th:PF12TBT:PC71BM ternary system with complementary polymer absorption spectra and efficient energy transfer from PF12TBT to PTB7-Th was anticipated to have an outstanding performance. However, only a limited improvement in the power conversion efficiency (PCE) was achieved when the ternary devices were processed from CB/DIO. This is because large PC71BM domains formed with the addition of amorphous PF12TBT and the PF12TBT molecules embedded in the large PC71BM domains served as trap sites. Constraining the formation of large PC71BM domains and avoiding PF12TBT molecules being fully embedded in PC71BM domains are needed for a better performance. Polymer pre-aggregation before liquid–liquid phase separation is beneficial to construct bicontinuous interpenetrating networks with proper phase-separated domains. Therefore, para-xylene was introduced into CB/DIO to cause a weak polymer–solvent interaction for enhanced PTB7-Th solution-phase aggregation. The enhanced PTB7-Th aggregation in the CB/PX/DIO solution restricted the extent of the liquid–liquid phase separation, and a well-developed polymer network formed with improved PTB7-Th crystallinity, which prevented large PC71BM domains from forming via fluid-phase Ostwald ripening in the liquid–solid phase separation stage. The appearance of PF12TBT emission and increased PTB7-Th emission in the ternary film processed from CB/PX/DIO suggested that fewer PF12TBT molecules were embedded in the PC71BM domains, and the energy transfer from PF12TBT to PTB7-Th was more efficient. Thus, PCE increased from 8.09% for binary blends processed from CB/DIO to 9.28% for ternary blends processed from CB/PX/DIO.

Macleaya cordata (Willd) R. Br. is a medicinal plant. The most important bioactive compounds of M. cordata are alkaloids that have many biological activities including antifungal, anti-inflammatory, and antitumor. In this study, an ionic-liquid-modified high-speed counter-current chromatography method was established to obtain alkaloids from the fruits of M. cordata. The conditions of ionic-liquid-modified high-speed counter-current chromatography, including solvent systems, the content of ionic liquid (1-butyl-3-methylimidazolium tetrafluoroborate [C4 mim][BF4 ]), and the posttreatment of the ionic liquid, were investigated. Five alkaloids protopine, allocryptopine, sanguinarine, 8-O-demethylchelerythrine, and chelerythrine were separated from the extract of the fruits using a high speed counter-current chromatography with two-phase solvent system composed of dichloromethane/methanol/0.3 mol/L hydrochloric acid aqueous solution/[C4 mim][BF4 ] (4:2:2:0.015, v/v). Their purities were 96.33, 95.56, 97.94, 96.22, and 97.90%, respectively. The results indicated that a small amount of ionic liquids as modifier of the two-phase solvent system could shorten the separation time and improve the separation efficiency of the alkaloids from the fruits. The ionic-liquid-modified high-speed counter-current chromatography would provide a feasible way for highly effective separation of alkaloids from natural products.

Purpose: neoMONARCH assessed the biological effects of abemaciclib in combination with anastrozole in the neoadjuvant setting. Patients and Methods: Postmenopausal women with stage I–IIIB HR+/HER2− breast cancer were randomized to a 2-week lead-in of abemaciclib, anastrozole, or abemaciclib plus anastrozole followed by 14 weeks of the combination. The primary objective evaluated change in Ki67 from baseline to 2 weeks of treatment. Additional objectives included clinical, radiologic, and pathologic responses, safety, as well as gene expression changes related to cell proliferation and immune response. Results: Abemaciclib, alone or in combination with anastrozole, achieved a significant decrease in Ki67 expression and led to potent cell-cycle arrest after 2 weeks of treatment compared with anastrozole alone. More patients in the abemaciclib-containing arms versus anastrozole alone achieved complete cell-cycle arrest (58%/68% vs. 14%, P < 0.001). At the end of treatment, following 2 weeks lead-in and 14 weeks of combination therapy, 46% of intent-to-treat patients achieved a radiologic response, with pathologic complete response observed in 4%. The most common all-grade adverse events were diarrhea (62%), constipation (44%), and nausea (42%). Abemaciclib, anastrozole, and the combination inhibited cell-cycle processes and estrogen signaling; however, combination therapy resulted in increased cytokine signaling and adaptive immune response indicative of enhanced antigen presentation and activated T-cell phenotypes. Conclusions: Abemaciclib plus anastrozole demonstrated biological and clinical activity with generally manageable toxicities in patients with HR+/HER2− early breast cancer. Abemaciclib led to potent cell-cycle arrest, and in combination with anastrozole, enhanced immune activation.

To investigate the effects and underlying mechanisms of Panax quinquefolium saponin (PQS) on energy deficiency in hypoxia-reperfusion (H/R) induced cardiomyocytes. The H/R injury involved hypoxia for 3 h and then reperfusion for 2 h. Cardiomyocytes recruited from neonatal rat ventricular myocytes (NRVMs) were randomly divided into control, H/R, H/R+compound C (C.C), H/R+PQS, and H/R+C. C+PQS groups. BrdU assay, lactase dehydrogenase (LDH) leakage and early apoptosis rate were evaluated to assess cell damages. Contents of high energy phosphate compounds were conducted to detect the energy production. Protein expression levels of adenosine monophosphate-activated protein kinase a (AMPKα), glucose transporter 4 (GLUT4), phosphate fructose kinase 2 (PFK2), fatty acid translocase/cluster of differentiation 36 (FAT/CD36), and acetyl CoA carboxylase 2 (ACC2) in the regulatory pathways were measured by Western blotting. Immunofluorescence staining of GLUT4 and FAT/CD36 was used to observe the mobilization of metabolic transporters. PQS (50 mg/L) pretreatment significantly alleviated H/R-induced inhibition of NRVMs viability, up-regulation of LDH leakage, acceleration of early apoptosis, and reduction of energy production (P

Room temperature mesophases were achieved by blending donors 2,3,6,7,10,11-hexakis-(hexyloxy)-triphenylene (H6TP) with acceptors N , N ′-bis(1-heptyloctyl)-perylene-3,4,9,10-tetracarboxylic diimide (PDI) via charge transfer interactions and size match. Compared with H6TP (mesophase temperature range: 97 °C–51 °C) and PDI (119 °C–108 °C), H6TP/PDI = 1/2 (138 °C - room temperature), 1/1 (139 °C–40 °C) and 1/0.5 (130 °C–31 °C) blends showed increase of clearing points and decrease of crystallization temperatures with wide mesophase temperature ranges. Different from edge-on orientation of PDI and no preferred alignment of H6TP, face-on alignments of all mixtures films could be achieved and stable at room temperature by cooling from isotropic state. It was inferred that stabilised columnar mesophases of H6TP/PDI blends were caused by charge transfer (CT) interactions and size match of them in hexagonal columnar phases. The existence of CT interactions was demonstrated by upfield shifts of aromatic protons in the 1 H NMR spectra of H6TP/PDI blends solutions and obvious fluorescent quenching in the blends films.

The macroscopic alignment of conjugated polymers with low grain boundary is essential to carrier transport. We investigated the formation mechanism of the aligned films of the donor−acceptor copolymer of 3,6-bis(thiophen-2-yl)-N,N′-bis(2-octyl-1-dodecyl)-1,4-dioxo-pyrrolo [3,4-c]pyrrole and thieno- [3,2-b]thiophene (PDBT-TT) by solvent vapor enhanced drop-casting (SVE DC). The dichroic ratio (DR) of the SVE DC films was 4.83 which were higher than the drop-casted (DC) films (1.43). There were large areas of bright stripe-like zones in the optic microscopy morphology and parallel fibers in the microscopic morphology of the SVE DC films. The diffraction arcs of TEM images of the SVE DC films were nearly two relatively narrow spots. These phenomena suggested the SVE DC films were in alignment (several hundreds of micrometers). The stripe-like zones were formed along the contact line receding and were observed in situ during the SVE DC films formation. The parallel fibers were formed along the molecular backbones due to the molecular backbones were sheared to rearrange in alignment along the direction of the contact line receding and had enough time to assemble to aligned fibers and improve the crystallinity when the contact line receded slow (1 μm/s). The crystallinity and alignment were improved simultaneously via SVE DC.

The proper crystallinity and a balance between H-aggregation and J-aggregation are both necessary for the best performance of small molecule organic solar cells. It is well known that J-aggregation is favorable to form more excitons due to its narrower bad-gap, leading to a high photocurrent. While H-aggregation has a higher lowest excited level which could provide stronger driving force for exciton dissociation. However, for 7,7′-(4,4-bis(2-ethylhexyl)-4H-silolo[3,2-b:4,5-b′]dithiophene-2,6-diyl)bis(6-fluoro-4(5′-hexyl-[2,2′-bithiophen]-5-yl)benzo[c][1,2,5]thiadiazole) (p-DTS(FBTTh2)2)/[6,6]-phenyl-C71-butyric acid methyl ester (PC70BM) blend system, the crystallinity is very low and p-DTS(FBTTh2)2 is mainly in J-aggregation. Thus, increasing H-aggregation of p-DTS(FBTTh2)2 is an effective way to improve photovoltaic efficiency of p-DTS(FBTTh2)2/PC70BM system. In this paper, it was found that solvent vapor annealing (SVA) was an effective method to improve the crystallinity and the H-aggregation of p-DTS(FBTTh2)2 in blend film. Due to the prolonged time for self-organization, the crystallinity of p-DTS(FBTTh2)2 was enhanced. In addition, molecular motion ability of p-DTS(FBTTh2)2 was controlled and p-DTS(FBTTh2)2 could adjust its structure to form H-aggregation. As a result, the ratio of H/J could be tuned from 0.71 to 1.47 and the power conversion efficiencies (PCE) was improved from 2.64% to 6.63%.

The selection of sensitizer and its existence in the blend films are important to the performance of all-polymer ternary solar cells. Herein, all-polymer ternary solar cell devices, which used poly[4,8-bis(5-(2-ethylhexyl)thiophen-2-yl)benzo[1,2-b:4,5-b′] dithiophene-alt-3-fluorothieno[3,4-b]thiophene-2-carboxy-late] (PTB7-Th) as donor, poly[[N,N-bis(2-octyldodecyl)-napthalene-1,4,5,8-bis(dicarboximide)−2,6-diyl]-alt-5, 5′-(2,2′-bithiophene)] (N2200) as acceptor and poly[N−900-hepta-decanyl-2,7-carbazole-alt-5,5-(40,70-di-2-thienyl-20,10,30-benzothiadiazole) (PCDTBT) as sensitizer, are successfully demonstrated. The intermolecular interaction between donor PTB7-Th and sensitizer PCDTBT may lead to aggregation of PTB7-Th which decreases domain sizes and enlarges D/A effective interface area. In addition, the PCDTBT molecules also extend light absorption and cascaded energy levels of the ternary blend system. As a result, with 15% PCDTBT we get a power conversion efficiency of 5.11%, almost 20% higher than control device due to more favored exciton dissociation and higher charge transport efficiency. This study reveals a promising way to achieve high efficiency all-polymer solar cells using a low-band gap polymer PCDTBT. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016, 54, 1811–1819

The polymer regioregularity has a dramatic effect on device performance of organic photovoltaics in terms of material crystallinity and phase separated morphology. In this study, we investigated the molecular regioregularity induced morphological evolution of P3HT and PF12TBT blend thin films processed by solvents with different solubility and boiling point. After cast by good solvents chloroform (CF) and o-dichlorobenzene (oDCB), the regioregular (RR) and regiorandom (RA)-P3HT/PF12TBT blend films showed the similar phase separated morphology, namely fast solidification induced unsharp morphology for CF blend films and long-range demixing via spinodal decomposition within extending drying process for oDCB blend films, while the domain size for RA blend films were larger than those of RR blend films which could be attributed to easily disentanglement and diffusion of RA-P3HT molecules facilitated by smaller aggregation size in RA blend solutions. In addition, the morphology of RR blend films exhibited micro change while the RA blend films developed into long-range phase separation after thermal annealing for CF blend films which also confirmed the molecular diffusion induced morphological evolution. For marginal solvents p-xylene (XY), the RR P3HT showed obvious molecular aggregation in XY solution due to the intensive solvent–polymer interaction (Δδ) and high regioregularity and therefore the value of aggregation size (R a ) for RR-P3HT is as three times as that of RA-P3HT. After cast from XY solution, the RA blend films displayed droplet and bicontinuous morphology based on various blend ratios via spinodal decomposition. Meanwhile, the nanofiber morphology could be observed when the weight fraction of RR-P3HT beyond 10% in RR blend films, which resulting from the continuous growth of P3HT aggregations formed anterior of the phase separation in the film solidification process.