Ginkgo biloba and Its Chemical Components in the Management of Alzheimer's Disease.

The pathogenesis of Alzheimer's disease (AD), a degenerative disease of the central nervous system, remains unclear. The main manifestations of AD include cognitive and behavioral disorders, neuropsychiatric symptoms, neuroinflammation, amyloid plaques, and neurofibrillary tangles. However, current drugs for AD once the dementia stage has been reached only treat symptoms and do not delay progression, and the research and development of targeted drugs for AD have reached a bottleneck. Thus, other treatment options are needed. Bioactive ingredients derived from plants are promising therapeutic agents. Specifically, Ginkgo biloba (Gb) extracts exert anti-oxidant, anticancer, neuroplastic, neurotransmitter-modulating, blood fluidity, and anti-inflammatory effects, offering alternative options in the treatment of cardiovascular, metabolic, and neurodegenerative diseases. The main chemical components of Gb include flavonoids, terpene lactones, proanthocyanidins, organic acids, polysaccharides, and amino acids. Gb and its extracts have shown remarkable therapeutic effects on various neurodegenerative diseases, including AD, with few adverse reactions. Thus, high-quality Gb extracts are a well-established treatment option for AD. In this review, we summarize the insights derived from traditional Chinese medicine, experimental models, and emerging clinical trials on the role of Gb and its chemical components in the treatment of the main clinical manifestations of AD.

Pectin extracted from Premna Microphylla Turcz for preparation of a "sandwich" multi-property sensor film involved with deep eutectic solvent.

An acidic deep eutectic solvent (DES, choline chloride/citric acid) was used to efficiently extract edible pectin from Premna microphylla Turcz (PMTP) and further prepare the film sensor with the purpose of "four birds with one stone" with the roles of extractant, coalescent, conductivity promoter and bacteriostatic agent. The optimized extraction process accorded with pseudo second-order kinetics, which was carried out at 78.2 °C for 1.29 h with the solid-liquid ratio of 1:34.66 g/mL with the yield up to 0.8210 g/g. After comprehensive characterizations of pectin product, a simple casting method was used to prepare the PMTP-DES based composite film. It showed that the composite film has promising compatibility, smooth surface, good breathability and ideal homogeneity. After 30 power on/power off cycles at 10 V, it exhibited satisfied conductivity stability. Moreover, the PMTP-DES film could be simply assembled as the flexible visual temperature sensor, with sensitive response at breathing or finger touch; it exhibited the highest sensitivity of 134 %/°C when the external temperature changed from 15 to 55 °C. Besides, the composite film also has preferable antimicrobial activity. The whole results and findings were aimed to contribute for the raw material, composition, preparation, and functions of the existing flexible functional materials.

N/S element transformation modulating lithospheric microbial communities by single-species manipulation.

BACKGROUND: The lithospheric microbiome plays a vital role in global biogeochemical cycling, yet their mutual modulation mechanisms remain largely uncharted. Petroleum reservoirs are important lithosphere ecosystems that provide desirable resources for understanding microbial roles in element cycling. However, the strategy and mechanism of modulating indigenous microbial communities for the optimization of community structures and functions are underexplored, despite its significance in energy recovery and environmental remediation. RESULTS: Here we proposed a novel selective stimulation of indigenous functional microbes by driving nitrogen and sulfur cycling in petroleum reservoirs using injections of an exogenous heterocycle-degrading strain of Pseudomonas. We defined such bacteria capable of removing and releasing organically bound sulfur and nitrogen from heterocycles as "bioredox triggers". High-throughput 16S rRNA amplicon sequencing, metagenomic, and gene transcription-level analyses of extensive production water and sandstone core samples spanning the whole oil production process clarified the microbiome dynamics following the intervention. These efforts demonstrated the feasibility of in situ N/S element release and electron acceptor generation during heterocycle degradation, shifting microbiome structures and functions and increasing phylogenetic diversity and genera engaged in sulfur and nitrogen cycling, such as Desulfovibrio, Shewanella, and Sulfurospirillum. The metabolic potentials of sulfur- and nitrogen-cycling processes, particularly dissimilatory sulfate reduction and dissimilatory nitrate reduction, were elevated in reservoir microbiomes. The relative expression of genes involved in sulfate reduction (dsrA, dsrB) and nitrate reduction (napA) was upregulated by 85, 28, and 22 folds, respectively. Field trials showed significant improvements in oil properties, with a decline in asphaltenes and aromatics, hetero-element contents, and viscosity, hence facilitating the effective exploitation of heavy oil. CONCLUSIONS: The interactions between microbiomes and element cycling elucidated in this study will contribute to a better understanding of microbial metabolic involvement in, and response to, biogeochemical processes in the lithosphere. The presented findings demonstrated the immense potential of our microbial modulation strategy for green and enhanced heavy oil recovery. Video Abstract.

CO2 improves the anaerobic biodegradation intensity and selectivity of heterocyclic hydrocarbons in heavy oil.

Heterocyclic hydrocarbons pollution generated by oil spills and oilfield wastewater discharges threatens the ecological environment and human health. Here we described a strategy that combines the greenhouse gas CO2 reduction with microbial remediation. In the presence of nitrate, CO2 can improve the biodegradation efficiency of the resins and asphaltenes in heavy oil, particularly the biodegradation selectivity of the polar heterocyclic compounds by the newly isolated Klebsiella michiganensis. This strain encoded 80 genes for the xenobiotic biodegradation and metabolism, and can efficiently utilize CO2 when degrading heavy oil. The total abundance of resins and asphaltenes decreased significantly with CO2, from 40.816% to 26.909%, to 28.873% with O2, and to 36.985% with N2. The transcripts per million (TPM) value of accA gene was 57.81 under CO2 condition, while respectively 8.86 and 21.23 under O2 and N2 conditions. Under CO2 condition, the total relative percentage of N1-type heterocyclic compounds was selectively decreased from 32.25% to 22.78%, resulting in the heavy oil viscosity decreased by 46.29%. These results demonstrated a novel anaerobic degradation mechanism that CO2 can promote the anaerobic biodegradation of heterocyclic hydrocarbons in heavy oil, which provides a promising biotreatment technology for the oil-contaminated water.

Oxidative stress-triggered Wnt signaling perturbation characterizes the tipping point of lung adeno-to-squamous transdifferentiation.

Lkb1 deficiency confers the Kras-mutant lung cancer with strong plasticity and the potential for adeno-to-squamous transdifferentiation (AST). However, it remains largely unknown how Lkb1 deficiency dynamically regulates AST. Using the classical AST mouse model (Kras LSL-G12D/+;Lkb1flox/flox, KL), we here comprehensively analyze the temporal transcriptomic dynamics of lung tumors at different stages by dynamic network biomarker (DNB) and identify the tipping point at which the Wnt signaling is abruptly suppressed by the excessive accumulation of reactive oxygen species (ROS) through its downstream effector FOXO3A. Bidirectional genetic perturbation of the Wnt pathway using two different Ctnnb1 conditional knockout mouse strains confirms its essential role in the negative regulation of AST. Importantly, pharmacological activation of the Wnt pathway before but not after the tipping point inhibits squamous transdifferentiation, highlighting the irreversibility of AST after crossing the tipping point. Through comparative transcriptomic analyses of mouse and human tumors, we find that the lineage-specific transcription factors (TFs) of adenocarcinoma and squamous cell carcinoma form a "Yin-Yang" counteracting network. Interestingly, inactivation of the Wnt pathway preferentially suppresses the adenomatous lineage TF network and thus disrupts the "Yin-Yang" homeostasis to lean towards the squamous lineage, whereas ectopic expression of NKX2-1, an adenomatous lineage TF, significantly dampens such phenotypic transition accelerated by the Wnt pathway inactivation. The negative correlation between the Wnt pathway and AST is further observed in a large cohort of human lung adenosquamous carcinoma. Collectively, our study identifies the tipping point of AST and highlights an essential role of the ROS-Wnt axis in dynamically orchestrating the homeostasis between adeno- and squamous-specific TF networks at the AST tipping point.

Triphase dynamic extraction system involved with ionic liquid and deep eutectic solvent for various bioactive constituents from Tartary buckwheat simultaneously.

Friendly and highly efficient acquisition of multiple active components from foods is always of great interest. For synchronous extraction and separation flavonoids together with oil from Tartary buckwheat, a new triphase dynamic system was developed with magnetic nanofluid based on deep eutectic solvent (N888-Cl/lauric acid, 1:2) (liquid phase 1), ionic liquid ([C4mim]Br) aqueous solution (liquid phase 2) and raw material powders (solid phase). It was the first time that two types of green solvents were simultaneously applied and assisted by magnetic separation. Through the investigation on key properties and operational conditions of this system, the extraction efficiency of oil and flavonoids in liquid phase 1 and 2 was achieved as 35.29 and 41.17 mg/g respectively, which were higher than that of conventional ways. Then kinetic and thermodynamics mechanisms were discovered comprehensively. After targeted recovery, the spectral characterization and antioxidant activity of two products proved the effectiveness of the developed method.

Phytochemical Profiling, Isolation, and Pharmacological Applications of Bioactive Compounds from Insects of the Family Blattidae Together with Related Drug Development.

In traditional Chinese medicine (TCM), insects from the family Blattidae have a long history of application, and their related active compounds have excellent pharmacological properties, making them a prominent concern with significant potential for medicinal and healthcare purposes. However, the medicinal potential of the family Blattidae has not been fully exploited, and many problems must be resolved urgently. Therefore, a comprehensive review of its chemical composition, pharmacological activities, current research status, and existing problems is necessary. In order to make the review clearer and more systematic, all the contents were independently elaborated and summarized in a certain sequence. Each part started with introducing the current situation or a framework and then was illustrated with concrete examples. Several pertinent conclusions and outlooks were provided after discussing relevant key issues that emerged in each section. This review focuses on analyzing the current studies and utilization of medicinal insects in the family Blattidae, which is expected to provide meaningful and valuable relevant information for researchers, thereby promoting further exploration and development of lead compounds or bioactive fractions for new drugs from the insects.

Effect of Acupuncture on Time-Dependent of Muscle Endurance in Female Elbow Joint: A Randomized Controlled Trial.

Immediate characteristics of acupuncture have been confirmed by relevant studies; however, the current study on the time effect of acupuncture in improving upper limb forearm muscle endurance is still limited. The aims of this study are to explore: (1) whether real acupuncture (RA) can improve female forearm muscle endurance compared to sham acupuncture (SA) and (2) whether the changes in forearm muscle endurance after RA are time-dependent. Thirty-six healthy female students were recruited to participate in isokinetic tests of elbow flexion/extension (Flex/Ext) from maximum flexion to maximum extension as much as possible using an isokinetic dynamometer at a speed rate of 60°/sec. Participants in the RA group were stimulated at Quchi (LI11), Shousanli (LI10), Hegu (LI4), Xiaohai (SI8), Tianjing (SJ10), and Waiguan (SJ5) acupoints for 20 min, while the SA group needling was near at these acupoints. The values of the isokinetic parameters and surface electromyography (sEMG) signals were recorded before and after acupuncture. After RA, the isokinetic parameters values (average torque, work, power, and speed), the sEMG values at four major muscles, and the joint stiffness of elbow Flex/Ext were significantly increased (p < 0.05). The enhancement of forearm muscle endurance lasted approximately 7-21 min (from post1 to post3/post4), indicating that the effect of RA to improve elbow Flex/Ext muscle endurance is time-dependent. Therefore, this study found that RA can immediately improve the forearm muscle endurance of healthy women compared with SA, and this effect can last approximately 7-21 min until the acupuncture efficacy decreased or disappeared.

Immediate Effects of Acupuncture on Explosive Force Production and Stiffness in Male Knee Joint.

Acupuncture can improve explosive force production and affect joint stiffness by affecting muscle activation levels. This study aims to explore the effects of true acupuncture (TA) compared with sham acupuncture (SA) on the explosive force production and stiffness of the knee joint in healthy male subjects. Twenty subjects were randomly divided into the TA group (n = 10) and SA group (n = 10) to complete isokinetic movement of the right knee joint at a speed of 240°/s before and after acupuncture. Futu (ST32), Liangqiu (ST34), Zusanli (ST36), Xuehai (SP10), and Chengshan (BL57) were selected for acupuncture. The intervention of SA is that needles with a blunt tip were pushed against the skin, giving an illusion of insertion. The results showed that acupuncture and the intervention time had a significant interaction effect on knee joint explosive force and joint stiffness (p < 0.05). The average maximum (max) torque, average work, average power, average peak power and total work of the TA group increased significantly after acupuncture (p < 0.05), while the SA group did not (p > 0.05). Therefore, true acupuncture can immediately improve the explosive force and joint stiffness of the male knee joint by inducing post-activation potentiation (PAP) and/or De-Qi.

Selective separation of main flavonoids by combinational use of ionic liquid-loaded microcapsules from crude extract of Tartary buckwheat.

For selective adsorption of main flavonoids from crude Tartary buckwheat extract (rutin, 0.021 mg/mL; quercetin, 0.030 mg/mL; and kaempferol, 0.011 mg/mL), new ionic liquid-based sorbents were successfully prepared by encapsulating [Bmim]Br and [Bmim]Pro in regular spherical non-magnetic and magnetic microcapsules with polysulfone content of 8%, respectively. After appropriate loading process, the microcapsules were comprehensively characterized by infrared spectroscopy, thermogravimetry analysis and scanning electron microscopy. Then the separation strategy was designed to separate rutin and quercetin from kaempferol by combinational use of two kinds of IL-loaded microcapsules (ILLMs). The effects of solid-liquid ratio of ILLMs and extract, pH, time and adsorption temperature were all investigated. The experimental data fit well with the quasi-second-order kinetics model and Langmuir model. After desorption, target flavonoids were well recovered and the ILLMs showed good stability. As the result, a new IL-based separation technology for main flavonoids from food crop was developed for the first time.

Effect of Acupuncture on the Timeliness of Explosive Forces Generated by the Male Shoulder Joint.

Athletes aim to improve muscle strength to optimize sports performance and gain a competitive edge. Although modern sports medicine includes rehabilitation treatment methods for improving the explosive force of athletes, including acupuncture, a common alternative therapy, research on the effectiveness of acupuncture in improving the timeliness of explosive forces is limited. There is uncertainty regarding how long the effects of acupuncture treatment persist after treatment. Therefore, the purpose of this study was to explore the effect of acupuncture on the timeliness of explosive forces generated by the male shoulder joint. Eighteen healthy men underwent tests of shoulder adduction/abduction (Add/Abd) and flexion/extension (Flex/Ext) through an isokinetic measurement system. Acupuncture was used to stimulate LU1 (Zhongfu), LU3 (Tianfu), LU4 (Xiabai), LI14 (Binao), SJ13 (Naohui), SJ14 (Jianliao), and SJ12 (Xiaoluo), and the isokinetic parameters were recorded before and after acupuncture. After acupuncture, isokinetic muscle force parameters including the maximum (Max) torque, the average power, the average peak power, the average work, and the total work increased significantly (P < 0.05), whereas the average max torque Abd/Flex did not. Additionally, the preintervention values of the shoulder joints for Add/Abd and Flex/Ext were significantly greater than those at post 1 and post 2 (P < 0.05). The isokinetic results suggest that acupuncture can increase the explosive force of the male shoulder joint Add/Abd and Flex/Ext. Muscle cannot be fully activated when calcium saturation is below the maximal level. In this case, the postactivation potentiation (PAP) may enhance voluntary muscle force production. The effect of acupuncture is time-dependent, that is, the effects of acupuncture gradually weaken and disappear by approximately 10 minutes after acupuncture. Therefore, we suggest that acupuncture is used as an alternative therapy in sports competitions to increase the explosive forces of the shoulder joint, thereby improving sports performance.

Ionic liquid@ß-cyclodextrin-gelatin composite membrane for effective separation of tea polyphenols from green tea.

A new kind of multi-component membrane was prepared by combining gelatin solution, porogen and an inclusion complex of ionic liquid (IL) and beta-cyclodextrin (ß-CD) in a simple physical manner for selective separation of tea polyphenols (TPs) from green tea crude extracts. After screening, it was found that the resulting membrane containing the IL of dicationic N-vinylimidazole proline salt ([VIm]2C3[l-pro]2) had the excellent performance for the enrichment of the target molecules. Then the newly-developed film was comprehensively characterized by scanning electron microscopy, conductivity, thermogravimetry and spectral analysis. Under pressure driving, the adsorption from an aqueous solution of a mixture of TPs and theophylline on IL@ß-CD-Gel membrane showed that the adsorption capacity for TPs was 303.45 mg/g with removal percentages of 94.38%. The experimental data fit well with pseudo-second-order model and Freundlich model. By using this composite material, a new technology of membrane separation for selective adsorption of TPs was finally established.

Extraction and quantitative analysis of tropane alkaloids in Radix physochlainae by emulsion liquid membrane with tropine-based ionic liquid.

Emulsion liquid membrane (ELM) coupled with tropine-based ionic liquid was prepared and successfully adopted for the extraction and quantitative analysis of tropane alkaloids (TA) in Radix physochlainae. Effects of formation conditions of ELM were explored and then optimized; the ideal oil-water mass ratio was determined to be 1:2.5, chloroform, Span 80 and 0.05 mol L-1N-propyl-tropine hexafluorophosphate ([C3Tr][PF6]) aqueous solution were stirred for 30 min with the speed of 1500 r min-1. In order to extract and enrich TA with ELM efficiently, key factors related with their extraction efficiency such as stirring speed, volume of the extracts (feed solution), migration time and initial concentration of TA were systematically investigated. Under optimal conditions, 1.5 mL extracts containing 1.6 mg mL-1 of TA was stirred with ELM at 250 r min-1 for 5 min, the extraction efficiency of target alkaloid can reach 94.14%. Finally, the method could be used in quantitative analysis of TA in herbal material and patent medicine after demulsification. By comparison, application of ELM for the enrichment and quantitation of TA offers a more straightforward and effective strategy, which is expected to provide a meaningful reference for similar separation processes.

Systematic investigation for extraction and separation of polyphenols in tea leaves by magnetic ionic liquids.

BACKGROUND: Magnetic separation has become a mature industrial technique in many fields and its application in the food and agricultural fields is expected for further extension. Furthermore, there has been little application of magnetic ionic liquids in the preparation of bioactive products. In the present study, 0.8 mol L-1 C3 MIMFeCl4 in its aqueous solution was found to be ideal for the extraction of active constituents from tea leaves. After extraction, polyphenols, caffeine and ionic liquid were also satisfactorily separated from the crude extract by various easy operations. RESULTS: The average extraction efficiency of tea polyphenols could reach up to 185.38 g kg-1 and the recovery percent of the magnetic ionic liquid was 99.8% through an external magnetic field. The extraction process was more consistent with a pseudo-second order kinetic model. Moreover, C3 MIMFeCl4 had no effect on the stability of tea polyphenols, which was very different from ordinary ferric salt. The presence of magnetic ionic liquid had a positive effect on the antioxidant activity of the product. CONCLUSION: The developed method had a good performance for selective extraction together with separation of tea polyphenols and caffeine, which is expected in the preparation of more similar active components from food and agricultural resources as a useful multifunctional solvent. © 2018 Society of Chemical Industry.

Bioactivity-Guided Screening of Wound-Healing Active Constituents from American Cockroach (Periplaneta americana).

Ethanol extract (EE) from Periplaneta americana (PA) is the main ingredient of Kangfuxin, which is a popular traditional chinese medicine (TCM) and has long been used for the clinical treatment of burns, wounds and ulcers. We compared the wound-healing activities of three extracts of PA using cutaneous wound-healing in mice as the bioactivity model. These three extracts were EE, total polysaccharide and total protein. We also tracked bioactive fractions in the EE by organic reagent extraction, column chromatography and HPLC. Seven compounds were successfully identified from the water elution fraction of the EE of PA using UPLC-MS. Among these compounds, four compounds (P2, P3, P4, P5(1)) were first reported in PA. Some of these compounds have been previously reported to have various pharmacological activities that could contribute to the high wound-healing activity of PA.

Bionic multi-tentacled ionic liquid-modified silica gel for adsorption and separation of polyphenols from green tea (Camellia sinensis) leaves.

For the first time, a new kind of bionic multi-tentacled ionic liquid-modified silica gel was synthesized and used as selective adsorbent in the preparative separation of tea polyphenols (TP) from green tea leaves. It was found that silica particles with polyvinyl alcohol chains modified by N-methyl imidazole proline salt (PVA·Im+·Pro-@SiO2) had the excellent performance in selective adsorption as well as fine separation for target compounds. The new adsorbent exhibited high adsorption capacity and good reusability, meanwhile the antioxidant activity of TP could be improved through its efficient enrichment. It properties and adsorption mechanism were also investigated comprehensively and compared with those reported sorbents. Finally, the preparative separation of individual catechin from crude extracts was successfully achieved on the chromatographic column packed with PVA·Im+·Pro-@SiO2 particles and four main constituents were obtained successively. The study was expected to provide a new way for the effective separation of similar bioactive compounds.

Recent Research Progress in Natural Bioactive Constituents against Lipid Metabolic Diseases.

Lipid metabolic disorder refers to the dyslipidemia in the plasma. Abnormal working or lipid metabolism process leads to supernormal increase of one or multi kinds of lipids in plasma. It is a significant risk factor for many diseases and has become a serious danger to the mankind health. The clinical drugs adjusting lipid levels have a great variety in the market, side effects and adverse reactions. Meanwhile, many Chinese herbal medicines and natural medicines have the unnegligible role of regulating lipid metabolism, which become the research focus of medical workers in past decades. With advantages of fewer side effects, abundant resources and multi-target functions, terrestrial and marine bioactive constituents are proved as one of the important sources of the lead compounds in drug discovery and have been widely applied in the treatment and prevention of lipid metabolic diseases. In this paper, the recent advancements and current status of natural medicinal ingredients mainly based on lipid-lowering activities were reviewed in detail. Moreover, their bioactivity screening and important mechanisms in hyperlipemia progression were summarized and compared. It was also selectively introduced about related structural modification and new drug development on the basis of promising lead compounds. Finally, the current problems and possible prospects of natural constituents against lipid metabolism disorder in the future were discussed.

Restoration of Central Programmed Movement Pattern by Temporal Electrical Stimulation-Assisted Training in Patients with Spinal Cerebellar Atrophy.

Disrupted triphasic electromyography (EMG) patterns of agonist and antagonist muscle pairs during fast goal-directed movements have been found in patients with hypermetria. Since peripheral electrical stimulation (ES) and motor training may modulate motor cortical excitability through plasticity mechanisms, we aimed to investigate whether temporal ES-assisted movement training could influence premovement cortical excitability and alleviate hypermetria in patients with spinal cerebellar ataxia (SCA). The EMG of the agonist extensor carpi radialis muscle and antagonist flexor carpi radialis muscle, premovement motor evoked potentials (MEPs) of the flexor carpi radialis muscle, and the constant and variable errors of movements were assessed before and after 4 weeks of ES-assisted fast goal-directed wrist extension training in the training group and of general health education in the control group. After training, the premovement MEPs of the antagonist muscle were facilitated at 50 ms before the onset of movement. In addition, the EMG onset latency of the antagonist muscle shifted earlier and the constant error decreased significantly. In summary, temporal ES-assisted training alleviated hypermetria by restoring antagonist premovement and temporal triphasic EMG patterns in SCA patients. This technique may be applied to treat hypermetria in cerebellar disorders. (This trial is registered with NCT01983670.).

Thalamocortical Sensorimotor Circuit Damage Associated with Disorders of Consciousness for Diffuse Axonal Injury Patients.

The relationship of structural and functional brain damage and disorders of consciousness (DOC) for diffuse axonal injury (DAI) is still not fully explored. We employed diffusion tensor imaging (DTI) and resting-state fMRI (RS-fMRI) to examine the changes of resting activations and white matter (WM) integrity for DAI with DOC. WM damages were observed in the body and genu of the corpus callosum, right external capsule (EC) and superior corona radiate (SCR), left superior cerebellar peduncle (SCP) and posterior thalamic radiation (PTR). The RS-fMRI revealed augmented amplitude of low-frequency fluctuation (ALFF) in the anterior cingulate cortex, hippocampus, insula, amygdala and putamen, and reduced ALFF in the precuneus, thalamus, pre-central and post-central gyri. Correlation analysis identified positive associations between the Glasgow Coma Scale (GCS) and activation of the precuneus and between GCS and DTI measurements in the left PTR and SCP, but a negative correlation was found between GCS and activation of the thalamus. Cross modality association analyses indicated that activations of the amygdala and postcentral gyrus were correlated with DTI measurements of the right EC and left PTR respectively. These results implicate that the WM damages in thalamocortical sensorimotor circuit and aberrant brain activity responding to self-awareness and sensation are critical factors to DOC, which expand the current understanding of the neural mechanisms underlying DAI.