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Various research showed that antioxidants can effectively overcome the damage caused by free radicals to human health. Therefore, antioxidants are identified as one of the main directions in the development of health care and cosmetics products due to high demand in the market. This review mainly focuses on the phycocyanin, a type of natural antioxidant mainly found in cyanobacteria. This mini review summarizes the phycocyanin sources and numerous extraction methods of phycocyanin along with the analytical methods and determine its ability to suppress free radicals. Phycocyanin has been proven to play an important role in scavenging free radicals and enhancing the body’s antioxidant capacity. However, there is a lack of long-term randomized clinical trial results that can be used as evidence in showing the benefits of phycocyanin. The existing phycocyanin extraction methods using solvents, ultrasonic-assisted, freeze-thaw, etc. can extract high-quality phycocyanin efficiently and quickly. Scientists are also trying to incorporate advanced technologies, such as "Industry 4.0" to optimize and enhance the industrial production of phycocyanin. Lastly, this review also describes the difficulties faced during the phycocyanin production or extraction process and financial obstacles in order to achieve the popularization of phycocyanin.

Background. Diabetes mellitus (DM) is a group of metabolic diseases characterized by hyperglycemia, which can induce the development of atherosclerosis (AS). Calcification of vascular smooth muscle cells (VSMCs) exerts an important role in the process of AS. In this study, the effects of liraglutide (LIRA) on VSMC under high-glucose condition and its mechanism were explored. Method. After VSMC was treated by high glucose with or without LIRA in vitro, the alkaline phosphatase (ALP) activity was measured by the detection kit, osteogenic marker protein expression was detected by Western blotting, and calcification was determined by alizarin red staining. Subsequently, the DM rat model was established and the ALP activity, calcification, and osteogenic marker proteins were determined in vivo. Immunohistochemical (IHC) staining and hematoxylin-eosin staining were performed on the thoracic aorta of DM rats. Result. The positive rate of SMα-actin expression in the DM + AS group was significantly lower than that in control rats, but LIRA administration increased the positive rate in the model. The expression of Cbfα-1 and OPN in the DM + AS group was significantly higher than that in the control group, while it was decreased after treatment of LIRA. The ALP activity and calcium content were increased in DM + AS rats, and the treatment of LIRA decreased the phenotypes in the rats, so as to delay the progression of AS in DM rats. Meanwhile, LIRA inhibited the ALP activity, upregulated SM-α expression, and downregulated expression of OPN and Cbfα-1 in VSMC under high-glucose (HG) conditions. Mechanically, HG-enhanced ALP activity, AKT, and ERK phosphorylation were inhibited by LIRA, PI3K antagonist LY294002, or ERK1/2 antagonist PD98059, in which cotreatment of LIRA with LY294002 and PD98059 could further enhance the effect of LIRA on VSMC, and GLP-1R antagonists reversed the phenotypes in the model. LIRA blocked the osteogenic transformation of VSMC through PI3K and ERK1/2 signaling pathways, which can be reversed by GLP-1R antagonists. Conclusion. LIRA inhibited the abnormalities in VSMC calcification mediated by the GLP-1R, which was related to PI3K/Akt and ERK1/2 MAPK pathways. Therefore, the prospect and significance of LIRA in the treatment of DM complicated with AS were clarified.

This study presented a novel methodology to predict microalgae chlorophyll content from colour models using linear regression and artificial neural network. The analysis was performed using SPSS software. Type of extractant solvents and image indexes were used as the input data for the artificial neural network calculation. The findings revealed that the regression model was highly significant, with high R

Objectives Patients with psychiatric disorders have an increased risk of cardiovascular pathologies. A bidirectional feedback model between the brain and heart exists widely in both psychotic and nonpsychotic disorders. The aim of this study was to compare heart rate variability (HRV) and pulse wave velocity (PWV) functions between patients with psychotic and nonpsychotic disorders and to investigate whether subgroups defined by HRV and PWV features improve the transdiagnostic psychopathology of psychiatric classification. Methods In total, 3448 consecutive patients who visited psychiatric or psychological health services with psychotic (N = 1839) and nonpsychotic disorders (N = 1609) and were drug-free for at least 2 weeks were selected. HRV and PWV indicators were measured via finger photoplethysmography during a 5-minute period of rest. Canonical variates were generated through HRV and PWV indicators by canonical correlation analysis (CCA). Results All HRV indicators but none of the PWV indicators were significantly reduced in the psychotic group relative to those in the nonpsychotic group. After adjusting for age, gender, and body mass index, many indices of HRV were significantly reduced in the psychotic group compared with those in the nonpsychotic group. CCA analysis revealed 2 subgroups defined by distinct and relatively homogeneous patterns along HRV and PWV dimensions and comprising 19.0% (subgroup 1, n = 655) and 80.9% (subgroup 2, n = 2781) of the sample, each with distinctive features of HRV and PWV functions. Conclusions HRV functions are significantly impaired among psychiatric patients, especially in those with psychosis. Our results highlight important subgroups of psychiatric patients that have distinct features of HRV and PWV which transcend current diagnostic boundaries.

Many traditional Chinese medicines have been clinically proven to have good anticancer effects in recent years. Tripterygium wilfordii, as a classic anticancer herbal medicine, has good effects, bu...

Rise in human population and gradual decline in fossil fuels are increasing the demand for fuels and causing an upsurge in fuel prices and global warming. Concomitantly, consumers have raised their health awareness by taking various supplements, e.g. omega-3 fatty acids, thus calling for advanced nutraceuticals. Both issues are addressed by recent research on microalgae, which can be easily cultivated to produce lipidic biofuels and active drugs. Here, we reviewed the types and biosynthesis of microalgal lipids. We discuss genetic engineering and manipulation of cultivation conditions for enhancing lipid production. We present techniques for lipid extraction, with focus on green techniques. We also discuss the technical and economic challenges in manufacturing microalgae-based biofuels and other bioproducts at the industrial scale. Last, the market potentials and further research directions for future commercialization of microalgae lipids are discussed.

The capacity to diagnose cancer with the existing endogenous biomarkers remains limited because biomarkers usually act at the tumor site and are thus challenging to be detected directly from body fluids with high sensitivity and specificity, especially in the early stage of tumorigenesis. Here, we demonstrate an exogenous tumor-penetrating nanomarker composed of fluorescent nanoparticles conjugated with specific fluorescein-labeled peptides. The injectable nanomarkers perform four functions: they penetrate the tumor, target sites of cancer, cleave specific peptides by on-target protease, and drop off the labeled peptide into host urine for fluorescent detection. Sensitive in vivo tracking and monitoring of the cyclic process of the nanomarker was also accomplished. The nanomarker can noninvasively diagnose and monitor tumors with a volume of about 17 mm3 without invasive core biopsies. Enhanced capacity of early point-of-care detection for cancer is accomplished by receptor-dependent specificity of the signal generation in the urine compared with clinically used blood biomarkers.

The Hemipteran predator, Cyrtorhinus lividipennis, feeds on the eggs and nymphs of rice planthoppers and leafhoppers. We previously demonstrated that sublethal concentrations of imidacloprid stimulated the reproduction of C. lividipennis. Considering the essential roles of juvenile hormone (JH) in insect reproduction, we speculated that sublethal concentrations of imidacloprid may stimulate the reproduction of C. lividipennis by regulating JH level. To test this, we cloned C. lividipennis JH acid methyl transferase (ClJHAMT) and JH esterase (ClJHE), which are responsible for JH biosynthesis and degradation genes, respectively. We then knocked down ClJHAMT by injecting dsRNA into C. lividipennis nymphs and found that emerging female adults exhibited 88.8% lower expression of the vitellogenin gene (ClVg) and the number of eggs was reduced by 41.5% as compared with controls. Silencing ClJHE increased ClVg mRNA expression by 275.0% but did not affect fecundity. A sublethal concentration of imidacloprid (LC20) increased the JH titer in females by 35.3% and 60.6% at 24 and 48 h post-emergence, respectively. In treatments containing both imidacloprid and dsJHAMT, the silencing of CLJHAMT reduced the number of eggs produced by adult females by 21.4% as compared to the control (imidacloprid + dsGFP). Our results indicated that sublethal concentration of imidacloprid may induce C. lividipennis reproduction by upregulating JH level via JHAMT. The finding could provide valuable information for improved integration of C. lividipennis and insecticides in pest management.

The application and understanding of dendritic cell (DC) based immune cancer therapy are largely hindered by insufficient or improper presentation of antigens and the inability to track the homing of reprogrammed DCs to draining lymph nodes in real-time. To tackle these challenges, multi-functional and hierarchically structured silica nanospheres are rationally designed and fabricated, which encapsulate quantum dots to permit near infrared deep tissue imaging and are loaded with carcinoembryonic antigen messenger RNA (CEAmRNA) to enable stable and abundant antigen expression in DCs. After being injected into animals and inducing an antigen-specific immune response, the homing process of reprogrammed labelled DCs from peripheral tissues to draining lymph nodes can be simultaneously and precisely tracked. Significant inhibition of tumor growth is achieved via strong antigen-specific immune responses including induced DC maturation, enhanced T cell proliferation and cytotoxic T lymphocyte (CTL)-mediated responses. Both in vitro and in vivo experiments demonstrate the high effectiveness of this new strategy of imaging-guided cancer immunotherapy by using reprogrammed DCs as immunotherapeutic and tracking agents.

The persistent fight against global environmental threats and energy catastrophe is currently a major concern for the economic development of bioenergy across the entire country. Hence, traditional fuel-based reserves are overburdened to cope with the rapid energy crisis, necessitating an urgent need for an innovative carbon-neutral green-energy resource. In order to address these critical bottlenecks, microalgae with incredible metabolic versatility have paved the way for a pivotal attention towards sustainable biofuel production. However, due to high operational costs and low lipid productivity, the microalgae-based biofuel resource is still in its infancy. As a result, this problem can be overcome by incorporating engineered microalgal strains which can pave the way for significant lipid augmentation for biofuel production. Thus, our current review depicts an in-depth understanding of a multi-omics approach to microalgae, the broad scope of self-sustaining microalgae cultivation, lipid-extraction strategies, and conversion processes to improve economic commercialization in the bioenergy framework. The present review also provides a detailed analysis of the international and national status of bioenergy development by several federal agencies.

Background: Lipase is mainly extracted from animals, plants, fungi, and bacteria. The difficulty in extracting lipase from these organisms has led to the discovery of sustainable sources producing lipase. This study is the first to document the existence of lipase in the microalgae species from Umeå. Methods: Lipase in microalgae was extracted using liquid biphasic flotation as the protein homogenate from the extracts was found to contain lipase activity. The lipase activity was evaluated using colorimetric method with p-nitrophenyl palmitate as the substrate. The types, volumes, and concentrations of solvents as well as flotation kinetics, and the biomass weight were optimized. The experiment was conducted at optimal temperature and pH 7. Significant Findings: The optimized conditions for maximum lipase production were 400 mg of biomass, 10 min flotation time with flotation rate of 100 cc/min as well as 99.8% ethanol and 300 g/L ammonium sulphate concentration with volume ratio of 1: 0.83. Lipase recovery yield of the optimal LBF system was 70.3% with the separation efficiency of 82.0% and purification factor of 7.45. The findings revealed that the microalgae can be an ideal candidate for producing lipase and LBF serves as the platform for the development of large-scale extraction system. This work was supported by the Fundamental Research Grant Scheme, Malaysia [FRGS/1/2019/STG05/UNIM/02/2] and MyPAIRPHC—Hibiscus Grant [MyPAIR/1/2020/STG05/UNIM/1]. This research was also supported in full or in part with Kurita Asia Research Grant “21Pmy004–21R” provided by Kurita Water and Environment Foundation.

Cytorhinus lividipennis is a natural enemy of rice planthoppers and leafhoppers. Improving the fecundity of C. lividipennis will be helpful to improve its control effect on pests. However, little is known about the hormonal regulatory mechanism of reproduction in C. lividipennis. In the current study, we examined the role of 20-hydroxyecdysone (20E) biosynthesis relative gene Shadow in the reproduction of C. lividipennis. The complementary DNA sequence of ClSad is 2018 -bp in length with an open reading frame of 1398-bp encoding 465 amino acid residues. ClSad was readily detected in nymphal and adult stages, and highly expressed in the adult stage. ClSad was highly expressed in the midgut and ovaries of adult females. Moreover, RNA interference-mediated knockdown of ClSad reduced the 20E titers and ClVg transcript level, resulting in fewer fully developed eggs and a decrease in the number of eggs laid by dsSad-injected adult females within 15 days. These results suggest that ClSad plays a critical role in the reproduction of C. lividipennis. The present study provides insights into the molecular mechanism of the ClSad gene for the reproduction of C. lividipennis.

Inorganic perovskite nanocrystals (NCs) display attractive structural and optical properties, and have perspective in a wide range of optoelectronic applications. One interesting feature is their relatively slow hot carrier cooling rate, which allows to follow carrier dynamics in great detail with ultrafast spectroscopic techniques. In this talk, we present studies of the ultrafast carrier dynamics of perovskite NCs and assembled structures. Typically, when the excitation photon energy is increased, and thus the excess energy of the created carriers, the cooling time of the carriers towards the bandedge increases along. However, for CsPbI3 NCs, when the photon energy exceeds a certain threshold energy the cooling time starts to decrease, indicating that a competing relaxation pathway opens up which funnels carriers towards the bandedge. This threshold energy indicates the onset of a carrier multiplication process, in which absorption of a single photon leads to the creation of multiple electron-hole pairs. This process can also be inferred by following the carrier concentration, which shows a delayed build-up following the excitation pulse. The carrier dynamics in this system can be modeled within a framework of two competing cooling mechanisms. With the experimentally determined carrier cooling rate and threshold energy it is possible to extract the time-constant associated with the carrier multiplication process. Experiments on highly ordered CsPbBr3 NCs, so-called supercrystals, revealed how the photophysics are altered due to the inter-NC coupling as compared to the individual NCs. Next to a red-shift of the absorption and photoluminescence peak, the supercrystals show signatures of band-like states. The observation of a reduced Stokes-shift, decreased biexciton binding energy and increased carrier cooling rates, support the formation of delocalized states resulting from the coupling between individual NCs. These results open perspectives for assembled NCs for application in optoelectronic devices, with design opportunities exceeding the level of nanocrystal and bulk material.

Sustainable Development Goals (SDGs) have been part of much worldwide cooperation in engineering design, nutrients production that contributes towards a better and more sustainable future. This review intends to uncover a potential renewable source that could significantly contribute to various goals under the SDGs. The prospects of algae tackling the socio-ecological, economic, and environmental issues faced globally are discussed, along with approaches of algae that can be utilized to achieve many of the SDGs are reviewed and discussed. Moreover, the recent trends in terms of engineering application that co-relate to novel algae-based technology has also been included. Apart from that, algae have high oil content which is suitable for producing affordable and clean energy, which can be used for biofuels or electricity generation. The promising characteristics of algae will lead to its global acceptance and utilization for sustainability to help create a better world.

Bobbin tool friction stir welding (BT-FSW) is a variant of conventional friction stir welding (FSW). It can be used to weld complex curvature structures and closed sections by adding an extra shoulder instead of a rigid backing anvil, which expands the potential application of FSW in aerospace, railway, automotive and marine industries. BT-FSW has some significant advantages over conventional FSW such as no root flaws, full weld penetration, low stiffness requirements for machines and fixtures, balanced heat input, lower distortion and thus has broad prospects for development. At present, there have been numerous research reports on BT-FSW, but its widespread use is still restricted due to various factors such as tool life, process stability, control complexity and implementation cost. In this paper, the domestic and foreign research progress of BT-FSW is reviewed from four aspects of bobbin tool design and classification, temperature field and flow field during welding, microstructure and mechanical properties of welded joints as well as industrial application, and then the possible research hotspots of BT-FSW in the future are pointed out. This paper mainly aims to help researchers have a comprehensive and in-depth understanding of BT-FSW.

Various studies showed that the suppression of α-glucosidase activity can impede the glucose absorption in our body, and therefore, it can be used to treat type 2 diabetes. Hence, the compounds with anti-α-glucosidase have gained considerable attention because of their potential application in diabetes treatment. In previous literature studies, these anti-α-glucosidase compounds were extracted from plants and fungus. Less studies are being conducted to identify the anti-α-glucosidase compounds in the microbial community. In this study, 23 marine bacterial strains were screened for their potential to suppress the α-glucosidase activity. The highest inhibitory activity was exhibited by isolated L06 which was identified as Oceanimonas smirnovii EBL6. The cultivation conditions, such as temperature and pH, were optimized to increase the production of α-glucosidase inhibitors by Oceanimonas smirnovii EBL6 strain. The result findings showed that the highest yield of α-glucosidase inhibitors can be obtained at the culture time of 120 h, fermentation temperature of 30 °C, and pH 4.6. Under these conditions, the inhibitory activity of α-glucosidase can reach 81%. The IC50 of n-butanol extract was 13.89 μg/ml, while standard acarbose was 31.16 μg/ml. Overall, these findings suggest that Oceanimonas smirnovii produces α-glucosidase inhibitors and could been applied in the biochemical and medicinal fields in the future.

Waste cooking oil (WCO) is considered as one of the hazardous wastes because improper disposal of WCO can cause significant environmental problems such as blockages of drains and sewers as well as water or soil pollution. In this review, the physical and chemical properties of WCO are evaluated along with its regulations and policies in different countries to promote WCO refined biofuels. Blended WCO can be an auxiliary fuel for municipal solid waste incinerators while the heat produced is able to form superheated steam and subsequently generate electricity via combined heat and power system. Also, WCO contains high ratio of hydrogen atoms compared to carbon and oxygen atoms, making it able to be catalytically cracked, synthesizing hydrogen gas. WCO-based biodiesel has been traditionally produced by transesterification in order to substitute petroleum-based diesel which has non-degradability as well as non-renewable features. Hence, the potentials of hazardous WCO as a green alternative energy source for electricity generation, hydrogen gas as well as biofuels production (e.g. biodiesel, biogas, biojet fuel) are critically discussed due to its attractive psychochemical properties as well as its economic feasibility. Challenges of the WCO utilization as a source of energy are also reported while highlighting its future prospects.

Global plastic pollution has been a serious problem since many years and micro (nano) plastics (MNPs) have gained attention from researchers around the world. This is because MNPs able to exhibit toxicology and interact with potentially toxic elements (PTEs) in the environment, causing soil toxicity. The influences of MNPs on the soil systems and plant crops have been overlooked despite that MNPs can accumulate in the plant root system and generate detrimental impacts to the terrestrial environments. The consumption of these MNPs-contaminated plants or fruits by humans and animals will eventually lead to health deterioration. The identification and measurement of MNPs in various soil samples is challenging, making the understanding of the fate, environmental and ecological of MNPs in terrestrial ecosystem is limited. Prior to sample assessment, it is necessary to isolate the plastic particles from the environment samples, concentrate the plastic particles for analysis purpose to meet detection limit for analytical instrument. The isolation and pre-concentrated steps are challenging and may cause sample loss. Herein, this article reviews MNPs, including their fate in the environment and toxic effects exhibited towards soil microorganisms, plants and humans along with the interaction of MNPs with PTEs. In addition, various analysis methods of MNPs and management of MNPs as well as the crucial challenges and future research studies in combating MNPs in soil system are also discussed.

Oil pollution which results from industrial activities, especially oil and gas industry, has become a serious issue. Cinder beats (CB), coconut fiber (CF) and polyurethane foam (PUF) are promising immobilization carriers for crude oil biodegradation because they are inexpensive, nontoxic, and non-polluting. The present investigation was aimed to evaluate this advanced technology and compare the efficiency of these immobilization carriers on supporting purple phototrophic bacterial (PPB) strains in hydrocarbon biodegradation of crude oil contaminated seawater. The surface of these biocarriers was supplemented with crude oil polluted seawater and immobilized by PPB strains, Rhodopseudomonas sp. DD4, DQ41 and FO2. Through scanning electron microscopy (SEM), the bacterial cells were shown to colonize and attach strongly to these biocarriers. The bacteria-driven carrier systems degraded over 84.2% supplemented single polycyclic aromatic hydrocarbons (PAHs). The aliphatic and aromatic components in crude oil that treated with carrier-immobilized consortia were degraded remarkably after 14 day-incubation. Among the three biocarriers, removal of the crude oil by CF-bacteria system was the highest (nearly 100%), followed by PUF-bacteria (89.5%) and CB-bacteria (86.3%) with the initial crude oil concentration was 20 g/L. Efficiency of crude oil removal by CB-bacteria and PUF-bacteria were 86.3 and 89.5%, respectively. Till now, the studies on crude oil degradation by mixture species biofilms formed by PPB on different carriers are limited. The present study showed that the biocarriers of an oil-degrading consortium could be made up of waste materials that are cheap and eco-friendly as well as augment the biodegradation of oil-contaminated seawater.

An integrated aptamer macroarray functionalized with reduced graphene oxide (rGO) to specifically capture and sensitively detect cancer cells is reported. The capture for cancer cells is based on effective recognition of the modified rGO surface through the aptamer against epithelial cell adhesion molecule (EpCAM). The rough structure of rGO enhances morphologic interactions between rGO film interface and the cancer cells, while super-hydrophilicity of modified rGO hinders nonspecific cell capture. The synergistic interactions offer the aptamer macroarray high efficiency of cancer cell capture. By means of a turn-on fluorescence strategy based on the conformation change of the aptamer induced by the target recognition, the enriched cancer cells can be directly read out at excitation/emission wavelengths of 550/680 nm without washing, separation, and dying steps. The working range is 1 × 102 to 2 × 104 cells per mL with a detection limit of 22 cells per mL. The results indicate that the aptamer macroarray has a considerable foreground for early diagnosis, therapy, and monitoring of cancer.

Microalgae are autotroph organisms that utilise light energy to synthesize various high-value bioactive compounds such as polysaccharides, proteins and lipids. Due to its fast growth rate and capability to survive in harsh environment, microalgae nowadays are applied in various industrial areas. The process of obtaining microalgae-based biomolecules starts with the selection of suitable microalgae strain, cultivation, followed by downstream processing of the biomass (i.e., pre-treatment, harvesting, extraction and purification). The end products of the processes are biofuels and other valuable bioproducts. Nevertheless, low production yield and high-cost downstream processes are the emerging bottlenecks which need to be addressed in the upscaling of extracted compounds from microalgae biomass. To conclude, tremendous efforts are required to overcome these challenges to revolutionize microalgae into a novel and green factory of different bioactive compounds for industrial necessities to satisfy and fulfil global demands.

Sensitive detection, especially in situ monitoring of intracellular MMP-2, is extremely desirable for cancer early diagnosis, evaluation of therapy, and discovery of the new anti-cancer drug. Herein, a programmed microcapsule-type MMP-2 responsive nanosensor based on mesoporous silica nanoparticles (MSN) is developed to realize in situ imaging monitoring of intracellular MMP-2. In the wrapping anti-MMP-2 antibody sealed microcapsule-type nanosensor, a black hole fluorescence quencher (BHQ-3) is covalently combined onto the inner walls of the MSN mesopores, and the fluorescein Cy5 is loaded in the cavity of MSN, resulting in fluorescence “OFF” state. With the existence of MMP-2, the anti-MMP-2 antibody which acts as a “bio-lid” could detach from the surface of the nanosensor owing to the binding MMP-2 with the antibody, leading to the release of the fluorescein Cy5 to produce fluorescence “ON” state. The prepared programmed microcapsule-type MMP-2 responsive nanosensor is capable of sensitive in situ imaging monitoring of intracellular MMP-2 and is further verified by tracking the change of intracellular MMP-2 level in response to MMP-2-repressive drugs. Thus, the nanosensor give a platform for in vivo detection of biomarkers for diagnosis, evaluation of therapy, and discovery of the new anti-cancer drug.

The canonical Wnt-β-catenin signaling pathway arrests the differentiation of T cells and plays an important role in phenotypic maintenance of naive T cells and stem cell-like memory T cells in human peripheral blood, but its effect on tumor-infiltrating lymphocytes (TILs) from non–small cell lung cancer is little known. In this study, we showed that glycogen synthase kinase-3β inhibitor TWS119 has different effects on CD4+ and CD8+ T cells in TILs. TWS119 preserved the expansion of naive T cell and CD8+ stem cell-like memory T cells, and induced CD8+ effector T-cell proliferation in TILs. To further determine whether TWS119 impaired the effector function of TILs, TILs were stimulated with polyclonal stimulation, IL-2 and IFN-γ production were detected. Our data showed that TWS119 does not affect the production of IFN-γ in TILs compared with the control group; whereas TWS119 inhibited IFN-γ secretion of T cells from healthy donor. IL-2 production in CD4+ central memory T cells and CD4+ effector memory T cells from TILs was significantly increased with the TWS119 treatment; TWS119 also promoted the secretion of IL-2 in all cell subsets of CD8+ TILs. These findings reveal that TWS119 has a distinct effect on the proliferation and cytokine production of TILs, and provide new insights into the clinical application of TILs with TWS119 treatment for the adoptive immunotherapy.

Currently, nanosphere-based ligand fishing cannot be accomplished with imaging processing, although this step is important for real-time identification. Herein, a ligand fishing technique combined with real-time imaging is presented for the identification of ligands for heat shock protein 90α (Hsp 90α) from a complex matrix, Alisma plantago-aquatica Linn. crude extract, using Hsp 90α-functionalized mesoporous silica nanoparticle (MSN)-InP/ZnS quantum dot (QD) nanocomposites as a support material. Twenty ligands for Hsp 90α were screened, and their structures were identified by mass spectrometry. The activities of the ligands were verified by real-time imaging of cells apoptotic morphological changes. Quantitative analysis showed that Alisma plantago-aquatica Linn contained 8.19μg/g Alisol F, which regarded as one typical component of Alisma plantago-aquatica Linn, and the extraction ratio of Alisol F was 76.2%. The precision for five replicate measurements was 7.0% (RSD). The prepared nanocomposites were also used to screen proteins from a mixture of cellular extracts, and five proteins from HeLa cells were identified as potential client proteins of Hsp 90α.

A new rearranged lignan, asasiebolin (1), was isolated from a kind of traditional Chinese medicine Asarum sieboldii, together with two known lignans, L-sesamin and L-asarinin. Asasiebolin (1) contained a benzo[d][1,3]dioxole-5-carboxyl moiety linked to a hydroxymethyl at C-3 of the tetrahydrofuran core, which might be rearranged after a cleavage from C-4. The structure with relative configuration was elucidated by in-depth spectral methods.

Pain sensitization after partial infraorbital nerve transection (p-IONX) in mice not only presents in orofacial region, but also spreads to distant body parts. The roles of toll-like receptor 4 (TLR4) in orofacial pain and the spreading process are still unclear. Here, we found that mice with deficient TLR4 because of Tr4 gene point mutation (C3H/HeJ) or spontaneous deletion (C57BL/10ScNJ) developed tactile allodynia and thermal hyperalgesia in the vibrissal pad in a parallel way to their respective wild types (C3HeB/FeJ or C57BL/6J) after p-IONX. However, allodynia in the hind paw was absent in mice with TLR4 deficiency. Pharmacological antagonism of TLR4 with LPS-RS, administered either intracisternally or intrathecally, abrogated allodynia in the hind paw without affecting the hypersensitivity in the vibrissal pad and hyperalgesia in the hind paw. Although TNF-α expression was upregulated in both the medulla and lumbar cord, the expression of TLR4 downstream molecule MyD88 increased only in the lumbar cord after p-IONX in wild types. By contrast, hind paw hypersensitivity after partial sciatic nerve ligation was significantly attenuated by TLR4 deletion. The hypersensitivity, which did not spread to the vibrissal pad, was accompanied with upregulation of MyD88 in the lumbar cord rather than in the medulla. These results suggest that TLR4 participates in the spread of allodynia component of orofacial pain to distant body sites, but not trigeminal neuropathic pain or the spread of its hyperalgesia component. This study suggests that TLR4 may serve as a potential target for the management of widespread allodynia associated with orofacial pain.

Plants are known for their capacity to regenerate the whole body through de novo formation of apical meristems from a mass of proliferating cells named callus. Exogenous cytokinin and auxin determine cell fate for the establishment of the stem cell niche, which is the vital step of shoot regeneration, but the underlying mechanisms remain unclear. Here, we show that type-B ARABIDOPSIS RESPONSE REGULATORs (ARRs), critical components of cytokinin signaling, activate the transcription of WUSCHEL (WUS), which encodes a key regulator for maintaining stem cells. In parallel, type-B ARRs inhibit auxin accumulation by repressing the expression of YUCCAs, which encode a key enzyme for auxin biosynthesis, indirectly promoting WUS induction. Both pathways are essential for de novo regeneration of the shoot stem cell niche. In addition, the dual regulation of type-B ARRs on WUS transcription is required for the maintenance of the shoot apical meristem in planta. Thus, our results reveal a long-standing missing link between cytokinin signaling and WUS regulator, and the findings provide critical information for understanding cell fate specification.

BACKGROUND/PURPOSE The aim of our research was to investigate the potential role of brain-derived neurotrophic factor (BDNF) in diabetic retinopathy (DR). Measurement of serum circulating levels of BDNF and analysis of polymorphism of BDNF gene (Val66Met) were applied and compared with diabetic patients without DR. METHODS From February 2014 and March 2015, all eligible patients with Type 2 diabetic mellitus at our hospital were consecutively recruited (N = 404). Their serum BDNF levels were detected by enzyme-linked immunosorbent assay. BDNF val66met polymorphism genotyping was conducted according to the laboratory's standard protocol. At baseline, demographic and clinical data were taken. The relationship of BDNF with DR was investigated with the use of logistic regression models. Receiver operating characteristic curves were used to test the overall accuracy of BDNF and other markers. RESULTS Diabetic patients with DR and vision-threatening DR had significantly lower BDNF levels on admission (P < 0.0001 both). The BDNF genotyping results showed that there was no difference between the diabetic patients with DR and those without DR. Multivariate logistic regression analysis adjusted for common risk factors showed that serum BDNF levels were independent risk factors for DR (odds ratio = 0.86; 95% confidence interval [CI]: 0.80-0.92; P < 0.0001) and vision-threatening DR (odds ratio = 0.79; 95% CI: 0.75-0.85; P < 0.0001). Brain-derived neurotrophic factor improved the area under the receiver operating characteristic curve of the diabetes duration for DR from 0.69 (95% CI: 0.60-0.76) to 0.85 (95% CI: 0.79-0.90; P < 0.01) and for vision-threatening DR from 0.77 (95% CI: 0.67-0.87) to 0.86 (95% CI: 0.80-0.92; P < 0.01). CONCLUSION The present study demonstrated that, rather than Val66Met polymorphism, decreased serum levels of BDNF were associated with DR and vision-threatening DR in Chinese Type 2 diabetic patients, suggesting a possible role of BDNF in the pathogenesis of DR complications.

Adoptive cell therapy using autologous tumor-infiltrating lymphocytes (TILs) or genetically modified lymphocytes from TILs is a new effective approach, but the application of TIL immunotherapy is still limited in many solid tumors. Knowledge of the classification and function of TILs is important to develop personalized immunotherapy with TILs in non-small lung cancer (NSCLC). In this study, we show the characteristics of T-cell subsets in TILs isolated from NSCLC. CD3 CD8 CD45RA T cells outnumbered CD3 CD4 CD45RA T cells in CD45RA TILs, but it was the opposite in CD45RO TILs. Effector memory CD4 T cells predominated in CD4 TILs; about 10% of the stem cell-like memory T cells (Tscm) were detected in TILs. To further analyze their functions, we stimulated TILs from NSCLC patients by mitogens to examine cytokine production. Our data demonstrated that naive-phenotype T cells in TILs secret IFN-γ in abundance; TNF-α-producing T cells were significantly increased in TILs; there were more IL-17-expressing CD4 Tscm cells than other subtypes of CD4T cells in TILs. Our findings indicate that the CD4/CD8 naive-phenotype T cells and Tscm cells in TILs from lung cancer exhibit distinct composition and strong cytokine production. Attributes of Tscm cells from a naive-like T-cell population in TILs are the promising cell type for adoptive cell therapy in human lung cancer.