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The northward shift of Pyropia yezoensis aquaculture required the breeding of germplasms with tolerance to the oxidative stress due to the high light conditions of the North Yellow Sea area. The MPV17/PMP22 family proteins were identified as a molecule related to reactive oxygen species (ROS) metabolism. Here, one of the MPV17 homolog genes designated as PyM‐LP2 was selected for functional identification by introducing the encoding sequence region/reverse complementary fragment into the Py. yezoensis genome. Although the photosynthetic activity, the respiratory rate, and the ROS level in wild type (WT) and different gene‐transformed algal strains showed similar levels under normal conditions, the overexpression (OE) strain exhibited higher values of photosynthesis, respiration, and reducing equivalents pool size but lower intracellular ROS production under stress conditions compared with the WT. Conversely, all the above parameters showed opposite variation trends in RNAi strain as those in the OE strain. This implied that the PyM‐LP2 protein was involved in the mitigation of the oxidative stress. Sequence analysis revealed that this PyM‐LP2 protein was assorted to peroxisomes and might serve as a poring channel for transferring malate (Mal) to peroxisomes. By overexpressing PyM‐LP2, the transfer of Mal from chloroplasts to peroxisomes was enhanced under stress conditions, which promoted photorespiration and ultimately alleviated excessive reduction of the photosynthetic electron chain. This research lays the groundwork for the breeding of algae with enhanced resistance to oxidative stresses. [ABSTRACT FROM AUTHOR]

Stem cells have shown tremendous potential and vast prospects in the research of intervertebral disc (IVD) regeneration and repair, attracting considerable attention in recent years. In this study, a bibliometric analysis and visualization techniques were employed to probe and analyze the hotspots and frontiers of stem cell research in IVD regeneration and repair, aiming to provide valuable references and insights for further investigations. This study utilized the Science Citation Index Expanded from the Web of Science Core Collection database to retrieve and extract relevant literature records as research samples. Visual analysis tools such as VOSviewer 1.6.19, CiteSpace 6.2.R4, and bibliometric online analysis platforms were employed to construct scientific knowledge maps, providing a comprehensive and systematic exposition from various perspectives including collaboration networks, cocitation networks, and co-occurrence networks. A total of 1075 relevant studies have been published in 303 journals by 4181 authors from 1198 institutions across 54 countries/regions. Over the past 20 years, the field of research has witnessed a significant growth in annual publications and citations. China and the United States have emerged as the primary participants and contributors, with the AO Research Institute Davos, Zhejiang University, and Tokai University being the top 3 leading research institutions. The most productive and highly cited author is Sakai D, who is regarded as a key leader in this research field. The journals with the highest number of publications and citations are Spine and Biomaterials , which are considered to be high-quality and authoritative core journals in this field. The current research focuses primarily on the sources and selection of stem cells, optimization of transplantation strategies, mechanisms of IVD regeneration, and the combined application of stem cells and biomaterials. However, there are still some challenges that need to be addressed, including posttransplantation stability, assessment of regenerative effects, and translation into clinical applications. Future research will concentrate on the diversity of stem cell sources, the application of novel biomaterials, personalized treatments, and the development of gene editing technologies, among other cutting-edge directions. This study utilized bibliometric analysis and visualization techniques to unveil the hotspots and frontiers in the research on stem cells for IVD regeneration and repair. These research findings provide essential guidance and references for further experimental design and clinical applications. However, additional experiments and clinical studies are still needed to address the challenges and difficulties faced in the field of IVD regeneration and repair, thus offering novel strategies and approaches for the treatment of IVD diseases. [ABSTRACT FROM AUTHOR]

A type of photocatalytic agent graphitic carbon nitride (g‐C3N4) has been formed by the thermal polymerization of urea with citric acid, with various contents of C in its material (CN‐x). Through the characterization of its morphology, structure, chemical composition, and photoelectric properties, it is found that the introduction of C dopant enhances sunlight absorption and facilitates electron‐hole separation and charge transfer within the g‐C3N4 structure. By further optimizing the doping amount of C, the photocatalytic degradation rates of CN‐10 on Rh B, methylene blue and amaranth reached 97.2 %, 94.2 %, and 91.2 % within 40 min, which were 1.1 times, 1.3 times, and 2 times of the unmodified g‐C3N4, respectively. Sacrifice experiments showed that ⋅O2− and ⋅OH were the main active substances in the photocatalytic degradation of Rh B and amaranth. In the degradation of methylene blue, ⋅O2− and h+ were then the main active substances. [ABSTRACT FROM AUTHOR]

Skeletons play an important role in the human body, and can form gaps of varying sizes once damaged. Bone defect healing involves a series of complex physiological processes and requires ideal bone defect implants to accelerate bone defect healing. Traditional grafts are often accompanied by issues such as insufficient donors and disease transmission, while some bone defect implants are made of natural and synthetic polymers, which have characteristics such as good porosity, mechanical properties, high drug loading efficiency, biocompatibility and biodegradability. However, their antibacterial, antioxidant, anti-inflammatory and bone repair promoting abilities are limited. Flavonoids are natural compounds with various biological activities, such as antitumor, anti-inflammatory and analgesic. Their good anti-inflammatory, antibacterial and antioxidant activities make them beneficial for the treatment of bone defects. Several researchers have designed different types of flavonoid-loaded polymer implants for bone defects. These implants have good biocompatibility, and they can effectively promote the expression of angiogenesis factors such as VEGF and CD31, promote angiogenesis, regulate signaling pathways such as Wnt, p38, AKT, Erk and increase the levels of osteogenesis-related factors such as Runx-2, OCN, OPN significantly to accelerate the process of bone defect healing. This article reviews the effectiveness and mechanism of biomaterials loaded with flavonoids in the treatment of bone defects. Flavonoid-loaded biomaterials can effectively promote bone defect repair, but we still need to improve the overall performance of flavonoid-loaded bone repair biomaterials to improve the bioavailability of flavonoids and provide more possibilities for bone defect repair. [ABSTRACT FROM AUTHOR]

Abstract Aurones are a subclass of active flavonoids characterized with a scaffold of 2-benzylidene-3(2H)-benzofuranone. This type of chemicals are widely distributed in fruit, vegetable and flower, and contribute to human health. In this review, we summarize the natural aurones isolated from dietary plants. Their positive effects on immunomodulation, antioxidation, cancer prevention as well as maintaining the health status of cardiovascular, nervous system and liver organs are highlighted. The biosynthesis strategies of plant-derived aurones are elaborated to provide solutions for their limited natural abundance. The potential application of natural aurones in food coloration are also discussed. This paper combines the up-to-date information and gives a full image of dietary aurones. [ABSTRACT FROM AUTHOR]

The skin, the largest organ in the human body, mainly plays a protective role. Once damaged, it can lead to acute or chronic wounds. Wound healing involves a series of complex physiological processes that require ideal wound dressings to promote it. The current wound dressings have characteristics such as high porosity and moderate water vapor permeability, but they are limited in antibacterial properties and cannot protect wounds from microbial infections, which can delay wound healing. In addition, several dressings contain antibiotics, which may have bad impacts on patients. Natural active substances have good biocompatibility; for example, ginsenoside Rg3 has anti-inflammatory, antibacterial, antioxidant, and other biological activities, which can effectively promote wound healing. Some researchers have developed various polymer wound dressings loaded with ginsenoside Rg3 that have good biocompatibility and can effectively promote wound healing and reduce scar formation. This article will focus on the application and mechanism of ginsenoside Rg3-loaded dressings in wounds. [ABSTRACT FROM AUTHOR]

Diabetic wounds are typically chronic wounds and the healing process is limited by problems such as high blood glucose levels, bacterial infections, and other issues that make wound healing difficult. Designing drug-loaded wound dressings is an effective way to promote diabetic wound healing. In this study, we developed an SA/PVA nanofiber (SPS) containing Shikonin (SK) for the treatment of diabetic wounds. The prepared nanofibers were uniform in diameter, had good hydrophilicity and high water vapor permeability, and effectively promoted gas exchange between the wound site and the outside world. The results of in vitro experiments showed that SPS was effective in antimicrobial, antioxidant, and biocompatible. In vivo tests showed that the wound healing rate of mice treated with SPS reached 85.5 %. Immunohistochemical staining results showed that SPS was involved in the diabetic wound healing process through the up-regulation of growth factors (CD31, HIF-1α) and the down-regulation of inflammatory factors (CD68). Western blotting experiments showed that SPS attenuated the inflammation through the inhibition of the IκBα/NF-κB signaling pathway. These results suggest that SPS is a promising candidate for future clinical application of chronic wound dressings. [Display omitted] [ABSTRACT FROM AUTHOR]

The wound of diabetes has long-term excessive inflammation leading to wound fibrosis and scar formation. In the process of diabetic wound healing, good wound dressing is required for intervention. In this study, we designed a dihydromyricetin-loaded hydrogel (PCD) based on phellinus igniarius polysaccharide and l-arginine modified chitosan as an alternative material to promote diabetes wound healing. PCD had a uniform porous structure, good thermal stability, excellent mechanical properties, high water absorption, excellent antioxidant and anti-inflammatory activities and good biocompatibility and biodegradability. In addition, in the full-thickness skin trauma model of diabetes, PCD significantly inhibited the JNK signaling pathway to reduce inflammatory response, and significantly down-regulated the expression of TGF-β1, Smad2, Smad3 and Smad4 to directly inhibit the TGF-β/Smad signaling pathway to accelerate wound healing and slow down scar formation in diabetes mice. Therefore, PCD has a broad application prospect in promoting diabetes wound healing. [Display omitted] [ABSTRACT FROM AUTHOR]

Summary: Although several studies have shown the ability of l‐glutamate (glutamate) to mitigate the stress imposed by pathogens, the underlying mechanism is still in its infancy. To gain further knowledge, this study focussed on the effect of glutamate on primary nitrogen and carbon metabolisms during apple‐Penicillium expansum interaction. The obtained result showed that glutamate could effectively restrict blue mould rot development in apples, but had no direct impact on fungal growth in vitro. The application of glutamate increased the level of nitrogen in apples, resulting in a disrupted balance of carbon and nitrogen. Consistently, the key enzymes glutamine synthetase (GS) and glutamate synthase (GOGAT) involved in the GS/GOGAT cycle, and the deaminating activity of glutamate dehydrogenase (GDH), forming 2‐oxoglutarate and ammonium from glutamate, were promptly stimulated by glutamate. Interestingly, glutamate led to considerable consumption of the tricarboxylic acid (TCA) cycle intermediates, such as isocitric acid and citric acid, accompanied by the enhancement of malate dehydrogenase and succinate dehydrogenase activities. Collectively, exogenous application of glutamate might confer blue mould resistance in apples, at least in part, by redirecting host's primary nitrogen and carbon metabolisms, such as the activation of the GS/GOGAT cycle, deaminating activity of GDH and the TCA cycle. [ABSTRACT FROM AUTHOR]

Introduction: Macrophages are capable of exerting both proinflammatory and anti-inflammatory functions in response to distinct environmental stimuli, by polarizing into classically inflammatory state (M1) and anti-inflammatory phenotype (M2), respectively. The Wnt/β-catenin signaling plays an important role in the tissue homeostasis and immune regulations, including the macrophage polarizations. However, the molecular mechanism of Wnt/β-catenin signaling in regulating alveolar macrophage polarization in an inflammatory state remains unclear. Methods: The Wnt/β-catenin signaling-altered phenotypes of murine macrophage-like RAW264.7 cells in vitro and alveolar macrophage in vivo in both of naïve and lipopolysaccharide-induced inflammation states were accessed by immunoblotting and immunostaining assays. Results: The activation of Wnt/β-catenin signaling inhibited macrophage M1 polarization, but promoted alternative M2 polarization in murine RAW264.7 cells under a naïve state. Interestingly, in an LPS-induced inflammation condition, the enhanced Wnt/β-catenin activity suppressed both M1 and M2 polarizations in RAW264.7 cells in vitro, and primary alveolar macrophages of LPS-challenged mice in vivo. Molecular analysis further demonstrated an involvement of Stat signing in regulating Wnt/β-catenin signaling-altered polarizations in mouse alveolar macrophages. Conclusion: These results suggest a mechanism by which Wnt/β-catenin signaling modulates macrophage polarization in an inflammation state by regulating the Stat signaling pathway. [ABSTRACT FROM AUTHOR]

Optimal transition has been widely studied for tail‐sitter unmanned aerial vehicles (UAVs). However, since the derived optimal control can only be applied in an open‐loop form, unmodeled dynamics and external disturbances cannot be restrained. Aiming at this problem, this article presents a method to obtain optimal transition maneuvers in the presence of these uncertainties. The approach includes two steps: nonlinear trajectory optimization and robust trajectory tracking. For the trajectory optimization, the minimum altitude variation front and back transition trajectories are derived. Different from existing optimal transition studies, considerable actuator margins are reserved in this step. Thus the tail‐sitter possesses control efforts to perform closed‐loop corrections for uncertainties. For the trajectory tracking, a robust controller in the form of feedforward plus feedback is proposed. The feedforward term directly employs the derived optimal control to improve the dynamic response of the system. The feedback term adopts linear control and acceleration‐based compensator to place desired poles and restrain all uncertainties. To the authors' knowledge, this article is the first time to study the tail‐sitter robust transition control method considering the transition optimality and actuator margins. It is proved that the tracking errors converge into a specified neighborhood of the origin in a finite time. Simulation studies corroborate the performance of the optimal transition trajectories and the robust trajectory tracking controller. [ABSTRACT FROM AUTHOR]

The novel isomerase NsrQ, from Aspergillus novofumigatus, is a key enzyme in the biosynthesis of fungal tetrahydroxanthones and is responsible for dearomatizing cyclization to provide a tetrahydroxanthone scaffold. NsrQ catalyzes a two‐step isomerization reaction, involving the isomerization of allylic alcohol and subsequent inversion of configuration at the methyl group. We report on the biochemical and structural characterizations of NsrQ, and its homologue Dcr3, from Diaporthe longicolla. The crystal structures of NsrQ and Dcr3 revealed their similar overall structures, with a cone‐shaped α+β barrel fold, to those of the nuclear transport factor 2‐like superfamily enzymes. Furthermore, the structures of Dcr3 and NsrQ variants complexed with substrate analogues and the site‐directed mutagenesis studies identified the catalytic residues and the important hydrophobic residues in shaping the active site pocket for substrate binding. These enzymes thus utilize Glu and His residues as acid‐base catalysts. Based on these observations, we proposed a detailed reaction mechanism for NsrQ‐catalyzed isomerization reactions. [ABSTRACT FROM AUTHOR]

The novel isomerase NsrQ, from Aspergillus novofumigatus, is a key enzyme in the biosynthesis of fungal tetrahydroxanthones and is responsible for dearomatizing cyclization to provide a tetrahydroxanthone scaffold. NsrQ catalyzes a two‐step isomerization reaction, involving the isomerization of allylic alcohol and subsequent inversion of configuration at the methyl group. We report on the biochemical and structural characterizations of NsrQ, and its homologue Dcr3, from Diaporthe longicolla. The crystal structures of NsrQ and Dcr3 revealed their similar overall structures, with a cone‐shaped α+β barrel fold, to those of the nuclear transport factor 2‐like superfamily enzymes. Furthermore, the structures of Dcr3 and NsrQ variants complexed with substrate analogues and the site‐directed mutagenesis studies identified the catalytic residues and the important hydrophobic residues in shaping the active site pocket for substrate binding. These enzymes thus utilize Glu and His residues as acid‐base catalysts. Based on these observations, we proposed a detailed reaction mechanism for NsrQ‐catalyzed isomerization reactions. [ABSTRACT FROM AUTHOR]

Photosynthetic hydrogen induced by Chlamydomonas reinhardtii presents a promising pathway for producing clean and renewable biofuel. Whereas, this process is transient owing to the repression of [FeFe]-hydrogenase by the oxygen co-evolved in photosystem II. Pulsed light is employed to prevent O 2 accumulation and the activation of Calvin-Benson-Bassham cycle for sustainable H 2. While light quality significantly influences photosynthesis, the optimal wavelength for pulsed light-induced H 2 production remains not fully elucidated. Continuous irradiation at 660–670 nm performs poorly in H 2 production due to the activation of PSII, which is responsible for water oxidation. However, in this study, O 2 was removed using a combination of pulsed light and sulfite treatment. Among six light regimes with different wavelengths, pulsed light peaking at 660 nm resulted in the highest photo-H 2 evolution, reaching approximately 180 mL L−1 within three days. This value was 1.4 times higher than that achieved under conventionally white pulsed light. Exposure to 660 nm red pulsed light not only sustained high activity of PSII and hydrogenase but also reduced the gene expression levels of ribulose-1,5-bisphosphate carboxylase/oxygenase and ferredoxin-NADP+ reductase, which was supposed to attenuate the competing effects of CBB cycle. This finding optimizes an efficient light source for pulsed light-induced H 2 production and demonstrates a great potential for refining pulsed light parameters to improve H 2 production in algae in the future. [Display omitted] • The effects of pulsed light wavelengths on H 2 photoproduction were investigated. • Red pulsed light at 660 nm exhibits the highest level of H 2 photoproduction ability. • Red pulsed light at 660 nm maintains the high activity of both PSII and H 2 ase. • Red pulsed light at 660 nm suppresses the activity of CBB cycle. [ABSTRACT FROM AUTHOR]

The thymus is a critical immune organ with endocrine and immune functions that plays important roles in the physiological and pathological processes of the body. However, with aging, the thymus undergoes degenerative changes leading to decreased production and output of naive T cells and the secretion of thymic hormones and related cytokines, thereby promoting the occurrence and development of various age-associated diseases. Therefore, identifying essential processes that regulate age-associated thymic involution is crucial for long-term control of thymic involution and age-associated disease progression. Epithelial-mesenchymal transition (EMT) is a well-established process involved in organ aging and functional impairment through tissue fibrosis in several organs, such as the heart and kidney. In the thymus, EMT promotes fibrosis and potentially adipogenesis, leading to thymic involution. This review focuses on the factors involved in thymic involution, including oxidative stress, inflammation, and hormones, from the perspective of EMT. Furthermore, current interventions for reversing age-associated thymic involution by targeting EMT-associated processes are summarized. Understanding the key mechanisms of thymic involution through EMT as an entry point may promote the development of new therapies and clinical agents to reverse thymic involution and age-associated disease. • The thymus undergoes fibrosis and adipogenesis via the epithelial-mesenchymal transition (EMT) process. • TGF-β, cytokines, ROS, hormones, and microRNAs crucially modulate EMT, impacting thymic involution with age. • It is feasible to reverse age-associated thymic involution through interventions targeting EMT-related processes. [ABSTRACT FROM AUTHOR]

Blue light photobiomodulation (PBM) has attracted great attention in diminishing proliferation and inducing death of cancer cells recently. Osteosarcoma (OS) primarily occurring in children and adolescents, the limitations of drug resistance and limb salvage make it urgent to develop and identify new adjuvant therapeutic strategies. In this work, we attempted to research the anticancer effects and biological mechanisms of blue light PBM in human OS MG63 cells. The effects of various blue light parameters on MG63 cells indicated that suppressed cell proliferation and cell migration, induced cell apoptosis which are experimentally assessed using multiple assays including CCK, LDH, wound healing assay and Hoechst staining. Concurrently, the increases of ROS level and the inhibition of PI3K and AKT expression were identified under high-dose blue light PBM in MG63 cells. Meanwhile, SOCS3 is a major inducible anti-tumor molecule, we also found that blue light LED substantially promoted its expression. Thus, this study proposed that bule light PBM may be a hopeful therapeutic approach in OS clinical treatment in the future. • Enhancing light intensity or dose, blue light PBM effectively suppressed OS cell activity. • Blue light-induced OS cell apoptosis was correlated with elevated ROS and reduced MMP. • Enhanced Caspase 3 activity mediated blue light-induced apoptosis in OS cells. • SOCS3 protein was a key factor in blue light-induced apoptosis of OS cells. • High-level dose of blue light induced OS cells apoptosis by PI3K/AKT pathway suppression. [ABSTRACT FROM AUTHOR]

Introduction: Macrophages are capable of exerting both proinflammatory and anti-inflammatory functions in response to distinct environmental stimuli, by polarizing into classically inflammatory state (M1) and anti-inflammatory phenotype (M2), respectively. The Wnt/β-catenin signaling plays an important role in the tissue homeostasis and immune regulations, including the macrophage polarizations. However, the molecular mechanism of Wnt/β-catenin signaling in regulating alveolar macrophage polarization in an inflammatory state remains unclear. Methods: The Wnt/β-catenin signaling-altered phenotypes of murine macrophage-like RAW264.7 cells in vitro and alveolar macrophage in vivo in both of naïve and lipopolysaccharide-induced inflammation states were accessed by immunoblotting and immunostaining assays. Results: The activation of Wnt/β-catenin signaling inhibited macrophage M1 polarization, but promoted alternative M2 polarization in murine RAW264.7 cells under a naïve state. Interestingly, in an LPS-induced inflammation condition, the enhanced Wnt/β-catenin activity suppressed both M1 and M2 polarizations in RAW264.7 cells in vitro, and primary alveolar macrophages of LPS-challenged mice in vivo. Molecular analysis further demonstrated an involvement of Stat signing in regulating Wnt/β-catenin signaling-altered polarizations in mouse alveolar macrophages. Conclusion: These results suggest a mechanism by which Wnt/β-catenin signaling modulates macrophage polarization in an inflammation state by regulating the Stat signaling pathway. [ABSTRACT FROM AUTHOR]

Prenylated flavonoids are good drug candidates due to multiple biological activities and health benefits. Prenyltransferase is an important enzyme involved in the biosynthesis of prenylated flavonoids. In this work, a flavonoid prenyltransferase (AhPT1) from Artocarpus heterophyllus showed an unexpectedly metal ion-induced specificity to flavonoid substrates. AhPT1 could catalyse 6- C -prenylation of genistein when Mg2+ serving as cofactor. Its catalytic activity to 6-hydroxyflavone was undetectable. However, when Mn2+ was used instead of Mg2+, 5- C -prenylated 6-hydroxyflavone was generated with a high conversion rate. Mn2+ altered the regiospecificity of AhPT1 and turned it into a 5- C -prenyltransferase. 2′-Hydroxyl could improve the conversion rate of 6-hydroxyflavone, whereas 3′- or 4′-hydroxyl impaired the catalysis efficiency of AhPT1. NQIFDADID174 and DLTDVEGD305 were active motifs involved in substrate binding and catalysis. Asn166, Asp170, Asp174, Asp298, Asp301 and Asp305 in the active center were critical to the prenylation reaction. Unlabelled Image [ABSTRACT FROM AUTHOR]

Glycyrrhizae radix has been widely accepted as a functional food in Asia. Isoliquiritigenin is a characteristic bioactive chemical in this medicinal plant. In this work, the neuroprotective effect of isoliquiritigenin and the possible mechanisms were investigated. The results revealed that isoliquiritigenin exhibited better neuroprotective and antioxidant activities than quercetin, a commercial natural antioxidant. Isoliquiritigenin significantly inhibited the release of lactate dehydrogenase, and the generation of reactive oxygen species in H 2 O 2 -treated cells. The activities of superoxide dismutase, glutathione peroxidase and catalase were improved. The mRNA expression levels related to oxidative defense and cell apoptosis were reversed by isoliquiritigenin. Moreover, isoliquiritigenin might inhibit the cell apoptosis via ameliorating the loss of mitochondrial membrane potential and the change of nucleus morphology. Image 1 • Isoliquiritigenin has a good neuroprotective activity. • Isoliquiritigenin can regulate the antioxidant system. • Isoliquiritigenin inhibits the cell apoptosis. • The neuroprotective mechanism of isoliquiritigenin is revealed. [ABSTRACT FROM AUTHOR]

The present study investigated if c-MYC and high mobility group AT-hook 2 (HMGA2) expression was associated with prognosis of patients with pancreatic ductal adenocarcinoma (PDAC). A total of 102 patients undergoing surgery for PDAC were retrospectively reviewed. Immunohistochemistry was used to detect c-MYC and HMGA2 protein expression in PDAC and peritumoral tissue samples. Expression of c-MYC and HMGA2 was associated with clinicopathological characteristics and prognoses of patients with PDAC using multivariate analysis. HMGA2 and c-MYC protein expression was significantly higher in PDAC tissues compared with peritumoral tissue (P<0.001). HMGA2 and c-MYC expression was also significantly higher in patients with PDAC who had lymph node metastasis, invasion of regional tissues and tumor node metastasis (TNM) stage III or IV disease compared with those who had no lymph node metastasis, no invasion of regional tissues and TNM stage I or II disease (P<0.001). Multivariate logistic regression analysis was used to identify TNM stage (P=0.007) and invasion (P=0.003) as significant independent predictors of c-MYC expression (model AUC=0.8201), and lymph node metastasis (P=0.002) and invasion (P=0.003) as significant independent predictors of HMGA2 expression (model AUC=0.7638). Cox multivariate analysis showed that expression of c-MYC (P=0.019) and HMGA2 (P<0.001), TNM stage (P=0.014) and lymph node metastasis (P=0.032) were associated with reduced overall survival time. HMGA2 and c-MYC may be important biological markers and potential therapeutic targets involved in the tumorigenesis, metastasis, invasion and prognosis of PDAC. [ABSTRACT FROM AUTHOR]

Banana is a tropical fruit with good palatability and multiple health benefits. However, the fruit quality is readily deteriorated during postharvest storage. In this work, icariin was used to treat banana to maintain the fruit quality. NMR spectroscopy was applied to analyze the effect of icariin on the metabolite profiles of banana. It was found that the fruit quality of banana was well maintained after icariin treatment. The data of 1D and 2D NMR spectra revealed the composition of metabolites, whose contents greatly varied during storage. The first principal components included ethanol, acetic acid, saponin b, salsolinol, dopamine, glucose, and linoleic acid. After icariin treatment, the conversion of starch to α-d-glucose and β-d-glucose was delayed, and the production of γ-aminobutyrate, glutamine, and alanine increased. These results indicated that icariin could effectively maintain the fruit quality and delay the senescence of banana. [ABSTRACT FROM AUTHOR]

Inadequate angiogenesis and inflammation at the wound site have always been a major threat to skin wounds, especially for diabetic wounds that are difficult to heal. Therefore, hydrogel dressings with angiogenesis and antibacterial properties are very necessary in practical applications. This study reported a hydrogel (PCA) based on L-arginine conjugated chitosan (CA) and aldehyde functionalized polysaccharides of Phellinus igniarius (OPPI) as an antibacterial and pro-angiogenesis dressing for wound repair in diabetes for the first time. and discussed its possible mechanism for promoting wound healing. The results showed that PCA had good antioxidant, antibacterial, biological safety and other characteristics, and effectively promoted the healing course of diabetic wound model. In detail, the H&E and Masson staining results showed that PCA promoted normal epithelial formation and collagen deposition. The Western blot results confirmed that PCA decreased the inflammation by inhibiting the IKBα/NF-κB signaling pathway and enhanced angiogenesis by adjusting the level of HIF-1α. In conclusion, PCA is a promising candidate for promoting wound healing in diabetes. Graphic abstract. [Display omitted] [ABSTRACT FROM AUTHOR]

Highlights • Three polysaccharides were identified in banana by NMR. • Starch was disassembled and degraded during storage. • Arabinogalactan proteins could be a marker for banana quality. Abstract The degradation of cell wall polysaccharides is highly associated with the softening process of banana. In this work, banana was treated by morin to delay softening during storage. Water-soluble polysaccharides were extracted from banana pulp at four storage stages. Their levels increased when the banana was green, but decreased when turned to yellow. Three types of polysaccharides were identified by nuclear magnetic resonance spectroscopy, including starches, homogalacturonans and arabinogalactan proteins. (1 → 4)-α-D-galacturonan constructed the backbone of homogalacturonans, which was the leading water-soluble polysaccharide in the last stage. Starch was the dominant polysaccharide at all stages in morin-treated banana. Deassembly of insoluble starch granules and degradation of soluble starches were responsible for its high level in banana. Arabinogalactan proteins were only detected in late stages, and could be a marker for banana deterioration. The inhibited degradation of cell wall polysaccharides contributed to the preservative effect of morin. [ABSTRACT FROM AUTHOR]

Programmed death-1 (PD-1), a key immune checkpoint molecule, has been developed as an oncotherapy target for various carcinomas. However, treatment with anti-PD-1 elicited only a minimal effect in pancreatic ductal adenocarcinoma (PDAC). Subsequent studies revealed the existence of a subset of PD-1+ T cells coexpressing CD38 and CD101, representing a fixed dysfunctional subpopulation that are not able to be rescued by anti-PD-1 immunotherapy. However, whether this subpopulation of PD-1 expressing CD8+ T cells could be useful in predicting PDAC stage or prognosing survival is unknown. In this study, we used flow cytometry and immunofluorescence assay to analyze the expression of CD38 and CD101 in 183 clinical PDAC samples, including 84 of peripheral blood and 99 of surgical tissues. High coexpression of CD38/CD101 on peripheral PD-1+CD8+ T cells or tumor-infiltrating lymphocytes (TILs) was found to be most significantly correlated with Tumor/Node/Metastasis (T/N/M) classification and clinical stage, in contrast PD-1+CD8+ T cells could not correlate with T classification. CD38/CD101 co-repression on TILs also correlated with the poor survival in these PDAC patient samples. Our data suggest that CD38/CD101 might represent a more helpful biomarker than PD-1 alone for diagnosis and prognosis of PDAC. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • α-(1 → 6)- d -glucan was a chemical contributing to the health benefit of banana. • α-(1 → 6)- d -glucan was abundant in banana. • α-(1 → 6)- d -glucan had good immunostimulatory activities. Abstract Banana is a fruit widely accepted by people over the world. Besides having delicious taste, it shows multiple health benefits. In this work, the major polysaccharide was isolated from banana and purified. It was identified to be α-(1 → 6)- d -glucan. The in vivo immunomodulatory activity assay indicated that α-(1 → 6)- d -glucan could improve the immune status by elevating T cell proliferation, phagocytic function of macrophage, CD3+ T cell level, CD4+/CD8+ ratio, IL-6, IgG, IgM, TNF-α and hemolysin antibody levels. The immunostimulatory activities of α-(1 → 6)- d -glucan were similar to β-(1 → 3)- d -glucan, a clinical immunostimulatory drug. This work revealed that α-(1 → 6)- d -glucan was an important bioactive chemical for the immunostimulatory activity of banana. It could be used as a nutraceuticals candidate. [ABSTRACT FROM AUTHOR]

By using aryl-thiazoles as cyclometalated ligands and an oxadiazol-substituted amide as the ancillary ligand, three novel iridium(iii) complexes have been synthesized and characterized, and their photophysical and electrochemical properties have been investigated. Complexes 1–3 exhibit efficient phosphorescence emissions at 542, 555 and 585 nm with photoluminescence quantum yields (PLQYs) of 0.04, 0.03 and 0.02 in CH3CN solutions, respectively. In the 10 wt% doped 2,4-diphenyl-6-bis(12-phenylindolo)[2,3-a]carbazole-11-yl)-1,3,5-triazine (Dictrz) film, the PLQYs (0.88 for complex 1, 0.47 for complex 2 and 0.37 for complex 3) increase significantly owing to the great restriction of rotations and vibrations in the rigid host. The organic light-emitting diodes based on these complexes show good performance with maximum current efficiencies of 20.06, 22.20 and 13.45 cd A−1 and maximum power efficiencies of 13.54, 17.31 and 9.48 lm W−1 with CIE coordinates of (0.46, 0.53), (0.49, 0.50) and (0.59, 0.40) for complexes 1–3, respectively. [ABSTRACT FROM AUTHOR]

Estrogen receptors (ERs) are transcription factors highly involved in physiological development and metabolism in the human body. They also play important roles in the treatment of cancer and metabolic diseases. Chemicals that interact with ERs can be used to treat diseases and maintain health. Phytoestrogens are natural chemicals that have been documented to possess significant ER modulatory activities. However, since phytoestrogens usually exist at low quantities in nature, heterologous biosynthesis techniques have quickly developed in recent years in order meet the demands for needed therapeutic amounts. In this review, the performance of phytoestrogens as ER modulators is described along with recent advances in biosynthesis techniques. Highlights ERs are highly involved in physiological development and metabolism. They play important roles in actions of immunomodulation and neuroprotection. Phytoestrogens are effective for maintaining health and treating diseases through regulation of ER signaling pathway. Heterologous biosynthesis is a promising technique for phytoestrogens production. [ABSTRACT FROM AUTHOR]

Abstract Top-emission flexible organic light-emitting devices (TE-FOLEDs) are highly suitable for next generation display due to their numerous assets including top-emitting configuration and mechanical flexibility. One major challenge in TE-FOLEDs is to prepare a deformable and reflective bottom electrode capable of effective carrier injection. In this paper, a new strategy for efficient and foldable TE-FOLEDs is demonstrated. It is based on a highly conductive Ag-nanoparticles (Ag-NPs) modified graphite that is used as a flexible bottom electrode. The good reflectance to full-color emission (>59% over the whole visible wavelength range), ultralow sheet resistance (<5 Ω/sq), and high tolerance to mechanical bending (almost unchanged in resistance after bending 1000 times with an angle of ±90°) of the modified graphite synergistically constitute a breakthrough in the domain of TE-FOLEDs. The maximum current efficiencies reach 15.0, 50.2, 16.8 cd/A for red, green, blue emissions, respectively. Colorimetric gamut increased by 99.6% compared to bottom emission structure with the corresponding Commission Internationale de L'Eclairage (CIE) coordinates of the red/green/blue (R/G/B) devices. In particular, the TE-FOLEDs incorporating highly flexible graphite electrodes offer great mechanical durability and the initial brightness of 5000 cd/m can be maintained over 90% after bending for 1000 bending cycles. This approach is expected to open a new avenue for developing foldable displays. Graphical abstract Image 1 Highlights • The Ag nanoparticles modified graphite onto PET substrate was fabricated with high flexibility and good heat dissipation. • The R/G/BTE-FOLEDs exhibit high color purity and enhanced colorimetric gamut compared to bottom-emitting devices. • The high current efficiency of 15.0, 50.2 and 16.8 cd/A were achieved for R/G/B TE-FOLEDs with low efficiency roll-off. • The TE-FOLEDs show high flexibility after bending for 1000 cycles at the initial brightness of 5000cd/m2. [ABSTRACT FROM AUTHOR]

Unlike common orange fruit, Citrus reticulata Blanco ‘Chachiensis’ (CRB) is usually served as traditional herbal medicine and function food. It is an abundant source of bioactive polysaccharides which contribute to the health benefits of CRB. However, the structure information of polysaccharides still remains unknown. In this work, the leading polysaccharide (CRBP) was purified from CRB peel. The structure was identified by nuclear magnetic resonnance spectroscopy. The backbone was (1 → 4)-α-D-galacturonan, while the branch was α-L-Ara f -(1 → 5)-α-L-Ara f -(1 → . The molecular weight was calculated to be 55.4 kDa. The proposed structure was drawed as below. The cell assays indicated that CRBP was not toxic to macrophage cells, and could promote the NO production significantly in a dose-dependent manner. These results demonstrated that CRBP was a good candidate for functional food development. [ABSTRACT FROM AUTHOR]

Papaya is a fruit mainly grown in tropical and subtropical regions. The structural changes of polysaccharides are highly involved in the organoleptic property change of papaya. However, it remains unclear how the structure characteristics of water-soluble polysaccharides are changed during postharvest ripening. It is interesting to work on this topic. In this work, the dominant water-soluble polysaccharide in papaya was purified. It was identified to be α-(1 → 4)-D-galacturonan by NMR. It remained stable during postharvest ripening. β-(1 → 4)-D-galactan was only detected in fully green papaya. Once the postharvest ripening initiated, this polysaccharide was rapidly degraded. There were no significant differences in the structure changes of water-soluble polysaccharides for the naturally ripening papaya and ethylene-treated papaya. These results extended the understanding about the relationship between polysaccharide structure and papaya ripening during postharvest storage. [ABSTRACT FROM AUTHOR]

Motivation DNA N4-methylcytosine (4mC) modification is an important epigenetic modification in prokaryotic DNA due to its role in regulating DNA replication and protecting the host DNA against degradation. An efficient algorithm to identify 4mC sites is needed for downstream analyses. Results In this study, we propose a new prediction method named SOMM4mC based on a second-order Markov model, which makes use of the transition probability between adjacent nucleotides to identify 4mC sites. The results show that the first-order and second-order Markov model are superior to the three existing algorithms in all six species (Caenorhabditis elegans , Drosophila melanogaster , Arabidopsis thaliana , Escherichia coli , Geoalkalibacter subterruneus and Geobacter pickeringii) where benchmark datasets are available. However, the classification performance of SOMM4mC is more outstanding than that of first-order Markov model. Especially, for E.coli and C.elegans , the overall accuracy of SOMM4mC are 91.8% and 87.6%, which are 8.5% and 6.1% higher than those of the latest method 4mcPred-SVM, respectively. This shows that more discriminant sequence information is captured by SOMM4mC through the dependency between adjacent nucleotides. Availability and implementation The web server of SOMM4mC is freely accessible at www.insect-genome.com/SOMM4mC. Contact chenyuanyuan@njau.edu.cn or piancong@njau.edu.cn [ABSTRACT FROM AUTHOR]

Apigenin is a dietary flavonoid with known antioxidant and antitumor effects against several types of cancers by promoting cell death and inducing cell cycle arrest. Apigenin also regulates a variety of intracellular signal transduction pathways during apoptosis or autophagy. However, the precise mechanism underlying the anticancer effects of apigenin in liver cancer remains poorly understood. In this study, we demonstrated that apigenin has anticancer activity against hepatocellular carcinoma cells. Apigenin inhibited the cell growth and induced cell death in a dose- and time-dependent manner in HepG2 cells. We found that apigenin treatment increased the expression of LC3-II and the number of GFP-LC3 puncta. Moreover, inhibition of autophagy with 3-MA and Atg5 gene silencing strengthened apigenin-induced proliferation inhibition and apoptosis. Our data has indicated that apigenin-induced autophagy has a protective effect against cell death. Additionally, apigenin induced apoptosis and autophagy through inhibition of PI3K/Akt/mTOR pathway. Most importantly, in vivo data showed that administration of apigenin decreased tumor growth and autophagy inhibition by 3-MA significantly enhanced the anticancer effect of apigenin. Collectively, our results reveal that apigenin inhibits cell proliferation and induces autophagy via suppressing the PI3K/Akt/mTOR pathway. Our results also suggest combination of autophagy inhibitors and apigenin would be a potential chemotherapeutic strategy against hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Inhibition of the VEGF/VEGF receptor (VEGFR) and angiopoietin-2 (Ang-2)/TEK receptor tyrosine kinase (Tie-2) pathway is a potential target for tumor angiogenesis. We previously showed that a peptide AS16 which dually inhibits VEGFR/Ang-2 could reduce the tumor growth and decrease the number of microvessels in tumor. However, its short circulating half-life in the serum limits its clinical applications. In this study, as an effort to prolong the short in vivo half-life of AS16, we designed a fusion protein containing peptide AS16 and an IgG Fc fragment. Pharmacokinetic study also revealed that AS16-Fc has a prolonged circulating half-life of about 231 min in rats. We examined the effects of treatment on the tumor vasculature and immune cell populations, tumor growth, in both the MCA-205 and S180 tumor models. We found that AS16-Fc dramatically reduced tumor volume, vascular density and tumor-associated macrophages. Macrophages were identified as potential novel targets following anti-angiogenic therapy, our findings imply a novel role for anti-angiogenic peptide AS16-Fc. These findings indicate that AS16-Fc could be more effective on inhibiting tumor growth angiogenesis and tumor immune microenvironment than that of peptide AS16. [ABSTRACT FROM AUTHOR]

We present a validated liquid chromatography with tandem mass spectrometry method for simultaneous determination of 20-( S)-protopanaxatriol and its two oxidative stereoisomeric metabolites (20 S,24 S)-epoxy-dammarane-3,6,12,25-tetraol (M1) and (20 S,24 R)-epoxy-dammarane-3,6,12,25-tetraol (M2) in rat plasma. 20-( S)-Protopanaxatriol, M1, and M2 were extracted with methanol and separated on an ACQUITY HSS T3 column. The mass spectrometry detection was accomplished in selected reaction monitoring mode with precursor-to-product ion transitions of m/z 493.4→143.1 for M1 and M2, m/z 475.4→391.3 for 20-( S)-protopanaxatriol, and m/z 459.4→375.3 for 20-( S)-protopanaxadiol (internal standard). The method showed good linearity over the concentration ranges of 1-1000 ng/mL for 20-( S)-protopanaxatriol and 0.5-200 ng/mL for M1 and M2, with correlation coefficients of more than 0.995. The lower limits of quantification for 20-( S)-protopanaxatriol, M1, and M2 were 1, 0.5, 0.5 ng/mL, respectively. The intra- and interday precisions (RSD, %) were less than 10.41% while the accuracy (relative error, %) ranged from -3.14 to 8.73%. Under the current conditions, M1 and M2 were completely separated within 3 min. The validated assay was successfully applied to evaluating pharmacokinetic profiles of 20-( S)-protopanaxatriol, M1, and M2 in rat. [ABSTRACT FROM AUTHOR]

The acidic washing process is a commonly applied approach to extract heavy metals (e.g. Cu and Cd) from soils. It is difficult, however, to purify the subsequent acidic soil leachates containing heavy metals. In this study, we proposed using ubiquitous native periphytic biofilm to clean soil leachates containing high concentrations of Cu (II) and Cd (II) under extreme and moderate acidic conditions. Results showed that the high concentrations of Cu (II) and Cd (II) present in the soil leachates after being washed with the eluents, water and mixed acidic solution (MAS), display average removal ratios by periphytic biofilm of 80.5 and 65.7% for Cu (II), and 42.9 and 68.6% for Cd (II), respectively. The sustainably grown periphytic biofilm acclimated to the extremely acidic (∼3.0) and moderate (∼7.1–8.0) pH soil leachates with Cu (II) and Cd (II) via self-adjustment of the microbial community structure and carbon metabolic potential. In the MAS system, the inclusion of mine tailings containing CaO neutralized the extreme pH conditions. Our results suggest that using native periphytic biofilm is a promising and clean approach to remediate extremely acidic and moderate pH soil leachates containing Cu (II) and Cd (II). [ABSTRACT FROM AUTHOR]

Although numerous studies have reported the involvement of glutamate in plant abiotic stress, relatively little is known about the role of glutamate in plant defence against pathogens. To gain further knowledge, we investigated the effect of glutamate on Alternaria alternata in tomato fruit. A multidisciplinary approach was pursued, combining exogenous glutamate applications, enzymatic activity measurements and real-time quantitative PCR analysis. The results showed glutamate significantly reduced the disease incidence in tomato caused by A. alternata, by inducing resistance (Duncan’s test, p < 0.05). A large variety of defence-related enzymes and genes involved in the glutamine synthetase/glutamate synthase cycle, energy-generated metabolism, such as the γ-aminobutyric acid shunt, glycolysis and the tricarboxylic acid cycle, and the salicylic acid signalling pathway were activated by glutamate. The activation of these pathways as mentioned above might play a potential role in the resistance mechanisms underpinning glutamate-induced plant immunity. [ABSTRACT FROM AUTHOR]

Summary: Harvested banana undergoes rapid softening, which limits its shelf life. To delay softening, banana fruit was treated with hydrogen sulfide (H2S) emitted by 0.6 mm sodium hydrosulfide (NaHS) and stored at 15 °C for 16 days. The effects of H2S on cell wall degradation and other physiological characteristics were investigated. In comparison to control fruits, H2S‐treated bananas retained a higher level of fruit firmness, but lower hue values. Ethylene metabolism analysis suggested that H2S inhibited the production of ethylene and the accumulation of 1‐aminocyclopropane‐1‐carboxylic acid (ACC) and decreased the activities of ACC synthase (ACS) and ACC oxidase (ACO). Cell wall polysaccharides determination assays suggested that H2S treatment increased the proportion of HCl‐soluble pectin (HSP), NaOH‐soluble pectin (NSP), cellulose and hemicellulose but decreased water‐soluble pectin (WSP) in fruits. H2S treatment also inhibited the activities of polysaccharide degrading enzymes such as polygalacturonase (PG), pectin methylesterase (PME), pectin lyase (PL), cellulase (CL) and β‐galactosidase (β‐Gal). Transmission electron microscopy analysis suggested that H2S protected cell walls from structural breakdown. These results indicated that H2S is effective in delaying banana softening by regulating cell wall polysaccharide metabolism. [ABSTRACT FROM AUTHOR]

The study investigated the effect of γ -aminobutyric acid (GABA) on the control of alternaria rot in tomato fruit and the possible mechanism involved. Our results showed exogenous GABA could stimulate remarkable resistance to the alternaria rot, while it had no direct antifungal activity against Alternaria alternata . Moreover, the activities of antioxidant enzymes, including peroxidase, superoxide dismutase and catalase, along with the expression of these corresponding genes, were significantly induced in the GABA treatment. The obtained data suggested GABA induced resistance against the necrotrophic pathogen A. alternata , at least in part by activating antioxidant enzymes, restricting the levels of cell death caused by reactive oxygen species. Meanwhile, the key enzyme genes of GABA shunt, GABA transaminase and succinic-semialdehyde dehydrogenase, were found up-regulated in the GABA treatment. The activation of the GABA shunt might play a vital role in the resistance mechanism underpinning GABA-induced plant immunity. [ABSTRACT FROM AUTHOR]

An early diagnosis of lupus nephritis (LN) has an important clinical implication in guiding treatments of systemic lupus erythematosus (SLE) in clinical settings. In this study, the concentrations of Wnt-3A, Frizzled-8 (FZD-8), and Dickkopf-1 (DKK-1) of Wnt signaling, as well as their diagnostic values for accessing LN, were evaluated by ELISA in sera and urine of 111 SLE patients (31 with LN and 80 without LN) and 70 healthy cohorts. Significantly more abundances of DKK-1 protein were determined in both of sera and urine of SLE patients compared to healthy cohorts (p < 0.0001); in particular the serum DKK-1 concentration was even higher in LN-SLE patients relative to non-LN SLE subjects (p < 0.0001). Intriguingly, concentrations of above examined proteins in SLE patients showed no correlation between serum and urine. Moreover, a combination of DKK-1 with anti-dsDNA and/or levels of complement C3 and C4 could not increase the specificity and/or sensitivity for identification of patients with LN diseases, but both ROC curve and multiple-factor nonconditional logistic regression analysis showed that serum DKK-1 was considered better positive biomarker for identification of LN in SLE patients. These results imply that serum and/or urine DKK-1 may be a valuable and independent biomarker for identification of SLE patients with LN. [ABSTRACT FROM AUTHOR]

In past decades, the frequent emergence of offshore oil accidents and the increasing of soluble pollutants have caused enormous damage to the ecosystem. It is urgent to develop efficient oil-water separation and water purification materials. In this work, a superhydrophobic material on the pretreated cotton fabric is prepared by simple immersion in TiO 2 nanoparticles and stearic acid solution. The resultant composited fabrics not only exhibited considerable superhydrophobicity with a water static contact angle of 157.3° and a water shedding angle of 5° favorable for oil-water separation, but also achieved the excellent photocatalytic activity by the degradation of water-soluble pollutants under visible light irradiation. The degradation efficiency could reach 98.4% within 60 min under visible light irradiation. Additionally, the coated cotton fabrics have excellent self-cleaning and stain resistance properties. After more than ten-cycles tests, the composited fabrics still maintain favorable performance of oil-water separation and photocatalytic degradation, which proves the excellent reusability. In the light of the outstanding predominance of the multifunction cotton fabrics, this simple, cost-effective, environmentally friendly and suitable for large-scale production strategy can boost the development of multipurpose superwetting materials, providing great tantalizing potential for oily wastewater efficient purification and environmental remediation. [Display omitted] • Hydrophobic materials with photocatalytic activity were prepared by dipping modified titanium dioxide solution. • Facile fabrication of superhydrophobic/superoleophilic and photocatalytic membranes. • The obtained cotton fabrics can realize sustainable and high-speed wastewater purification. • Functional cotton fabrics have excellent self-cleaning, oil-water separation and stability. [ABSTRACT FROM AUTHOR]

The aim of this work was to study the bioremediation of agricultural solid waste leachates with high-concentrations of Cu (II) and Cd (II) after washing the wastes with water and Na 2 EDTA solution (0.2 M). Results indicate that Cu (II) and Cd (II) are mainly comprised of Cu 2 (OH) 2 2+ , Cu 3 (OH) 4 2+ , CuOH + , Cu(H 2 O) 4 (OH) 2 , Cd 2+ and CdOH + in the water-washed leachates and Cu(EDTA) 2− , Cu(HEDTA) − , Cd(EDTA) 2− and Cd(HEDTA) − in the Na 2 EDTA-washed leachates. Cu (II) removal efficiency by selected native periphyton from the water- and Na 2 EDTA-washed leachates were 80.5% and 68.4% respectively, and for Cd (II) it was 57.1% and 64.6%, because the periphyton was able to maintain a stable pH of the leachates and regulate its microbial composition and carbon metabolic capability to acclimate the chemical conditions of the leachates. This study provides a new biomeasure to treat leachates with high-concentration Cu 2+ and Cd 2+ , and contribute valuable insights into the relationships between periphyton characteristics and heavy metals. [ABSTRACT FROM AUTHOR]

The development of chemoresistance to cisplatin regimens causes a poor prognosis in patients with advanced NSCLC. The role of noncanonical Wnt signaling in the regulation of properties of lung cancer stem cells and chemoresistance was interrogated, by accessing capacities of cell proliferation, migration, invasion, and clonogenicity as well as the apoptosis in A549 cell lines and cisplatin-resistant A549 cells treated with Wnt5a conditional medium or protein kinase C (PKC) inhibitor GF109203X. Results showed that the noncanonical Wnt signaling ligand, Wnt5a, could promote the proliferation, migration, invasion, and colony formation in A549 lung adenocarcinoma cells and cisplatin-resistant A549/DDP cells and increase the fraction of ALDH-positive cell in A549/DDP cells. An exposure of cells to Wnt5a led to a significant reduction of A549/DDP cell apoptosis but not A549 cells. An addition of GF109203X could both strikingly increase the baseline apoptosis and resensitize the Wnt5a-inhibited cell apoptosis. Interestingly, an inhibition of Wnt/PKC signaling pathway could reduce properties of lung cancer stem cells, promote cell apoptosis, and resensitize cisplatin-resistant cells to cisplatin via a caspase/AIF-dependent pathway. These data thus suggested that the Wnt5a could promote lung cancer cell mobility and cisplatin-resistance through a Wnt/PKC signaling pathway and a blockage of this signaling may be an alternative therapeutic strategy for NSCLC patients with resistance to chemotherapies. [ABSTRACT FROM AUTHOR]

• Autonomous regulating the pathological microenvironment enables efficient probiotics colonization. • Improved probiotic bacteria to survive acid and bile salt attacks show 2.5-times enhanced intestinal mucosal adhesion. • The here described encapsulation method can be widely applied to a variety of bacteria. Transplanting beneficial bacteria to gut microbiome can positively modulate microbiome composition and is a promising strategy to prevent and treat diseases. However, oral probiotic delivery is challenged not only by the physiological microenvironment, but also by pathological microenvironment. Herein, we designed a S uper G ut M icroorganism (SGM) encapsulated with versatile self-assembly coating for enhanced intestinal colonization. SGM has a rapidly self-assembling coating of tannic acid and poloxamer 188 that not only resists the attack of the physiological microenvironment but more importantly, autonomously modulates the pathological microenvironment (e.g., scavenging inflammation-mediated ROS and taking iron away from pathogenic bacteria), which improves probiotic survival. In addition, the artificial coat mediates strong intestinal mucosal adhesion, enhancing the intestine colonization of probiotics especially in disease. SGM significantly improved the efficacy in the prevention and treatment of colitis in vivo. In dextran sulfate sodium (DSS) colitis mice, SGM showed an excellent anti-inflammatory effect, capacity to restore intestinal barrier functions, and to prompt the balance of gut flora. In Salmonella enterica serovar Typhimurium (STm) colitis mice, treatment with SGM resulted in 6.8-times less STm compared to uncoated probiotics. The SGM presented here are a new resource to create novel probiotic systems to treat and prevent microbiome related diseases. [ABSTRACT FROM AUTHOR]

Recent progress showed the potential of glutamate to regulate stress responses by affecting phytohormones homeostasis, but much remains to be explored. To decipher the role of ethylene in glutamate-induced resistance to Alternaria alternata , ethephon application, ethylene perception inhibitor (1-MCP) experiment and ethylene measurement were pursued. Concurrently, temporal alteration in ethylene biosynthesis and signaling pathways were transcriptionally analyzed in tomato fruit. Our data exhibited that ethylene conferred tomato fruit susceptibility rather than resistance to Alternaria alternata. The enhanced resistance in glutamate treatment was related to decreased ethylene production during the early stages of interaction, accompanied by lower expression levels of SlACS1 , SlACS2 and SlACO1 relative to the control. Interestingly, 1-MCP induced amounts of resistance similar to that observed in glutamate treatment, while ethylene receptors (SlETR3 and SlETR4), mitogen-activated protein kinase SlMPK3 and ethylene response factor SlERF1 were down-regulated by glutamate during infection. Collectively, antagonizing the ethylene biosynthesis or signaling might play a pivotal role in glutamate-induced resistance to the necrotrophic pathogen Alternaria alternata. • The negative role of ET in basal and glutamate-induced resistance to A. alternata. • Antagonizing ethylene biosynthesis may play a role in glutamate-resistance. • Glutamate-resistance may be linked to suppression of ET action. [ABSTRACT FROM AUTHOR]

The ubiquitous native periphyton was used to entrap Cu and Cd from paddy fields. Results showed that Cu- and Cd-hydrate species such as CuOH + , Cu 2 (OH) 2 2+ , CdOH + , and Cu 3 (OH) 4 2+ decreased with time in the presence of periphyton. When the initial concentrations of Cu and Cd were 10 mg/L, the heavy metal content in the periphyton fluctuated from 145.20 mg/kg to 342.42 mg/kg for Cu and from 101.75 mg/kg to 236.29 mg/kg for Cd after 2 h exposure. The concentration of Cd in periphytic cells varied from 42.93 mg/kg to 174 mg/kg after 2 h. The dominant periphyton microorganism species shifted from photoautotrophs to heterotrophs during the exposure of periphyton to Cu and Cd co-contamination. Although Cu and Cd could inhibit periphyton photosynthesis and carbon utilization, the periphyton was able to adapt to the test conditions. Cu and Cd accumulation in rice markedly decreased in the presence of periphyton while the number of rice seeds germinating was higher in the periphyton treatments. These results suggest that the inclusion of native periphyton in paddy fields provides a promising buffer to minimize the effects of Cu and Cd pollution on rice growth and food safety. [ABSTRACT FROM AUTHOR]

Caged siRNAs with a single photolabile linker and/or vitamin E (vitE) modification at the 5′ terminal were rationally designed and synthesized. These virtually inactive caged siRNAs were successfully used to photoregulate both firefly luciferase and GFP gene expression in cells with up to an 18.6-fold enhancement of gene silencing activity, which represents one of the best reported photomodulation of gene silencing efficiencies to date. siRNA tracking and vitE competition experiments indicated that the inactivity of vitE-modified siRNAs was not due to the bulky moiety of vitE; rather, the involvement of vitE-binding proteins has a large contribution to caged siRNA inactivation by preventing the dissociation of siRNA/lipo complexes and/or siRNA release. Further patterning experiments revealed the ability to spatially regulate gene expression through simple light irradiation. [ABSTRACT FROM AUTHOR]

Caged siRNAs with a single photolabile linker and/or vitamin E (vitE) modification at the 5′ terminal were rationally designed and synthesized. These virtually inactive caged siRNAs were successfully used to photoregulate both firefly luciferase and GFP gene expression in cells with up to an 18.6-fold enhancement of gene silencing activity, which represents one of the best reported photomodulation of gene silencing efficiencies to date. siRNA tracking and vitE competition experiments indicated that the inactivity of vitE-modified siRNAs was not due to the bulky moiety of vitE; rather, the involvement of vitE-binding proteins has a large contribution to caged siRNA inactivation by preventing the dissociation of siRNA/lipo complexes and/or siRNA release. Further patterning experiments revealed the ability to spatially regulate gene expression through simple light irradiation. [ABSTRACT FROM AUTHOR]

Silicosis is caused by the continuous inhalation of environmental silica dust. The repetitive exposure of silica induces airway epithelial cell injury, leads proliferative exhaustion of epithelial stem cells, ultimately results in the lung remodeling and the development of silicosis. The B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi1) is a pivotal transcription factor in stem cell self-renewal and proliferation of many tissues including the lung, but its role in the airway basal cell proliferation and differentiation during the pathogenesis of silicosis in lung has yet been investigated. In this study, the function of Bmi1 in airway basal cell proliferation and differentiation in response to silica challenge was investigated in lungs of silicosis mice and primary human bronchial epithelia cells (HBECs) exposed to silica dioxide (SiO 2). Results showed a decreased expression of Bmi1 protein, epithelial basal cell markers Krt14 and Krt5, club cell marker Clara cell secretory protein, and ciliated cell marker acetyl-α-tubulin in silicosis lungs, compared to healthy mice. In consistence, a persistent exposure of SiO 2 reduced the capacity of cell proliferation and differentiation in HBECs, as ascertained by the reduction of differentiated epithelial cell markers and BMI1 expression, while an increased P21-positive senescent cell fraction. Moreover, an overexpression of BMI1 in HBECs reduced the SiO 2 -senescent cells, enhanced the potency of cell proliferation and differentiation, and increased capacity of airway epithelial regeneration in response to the persistent exposure of SiO 2. These data suggest that Bmi1 is a key transcription factor engaging in maintaining the self-renewal, proliferation and differentiation of epithelial stem cells in lung during the development of silicosis disease. [ABSTRACT FROM AUTHOR]

Objective: To determine the variability in the recognition of normal sperm and various sperm defects using the strict criteria recommended by the World Health Organization (5th edition, 2010). Design: Sperm morphologic assessment by three experienced evaluators. Setting: Image processing laboratory and reproduction research institute. Patient(s): Semen donors from a sperm bank. Intervention(s): The morphology of 5,296 sperm was evaluated using statistical analyses of variability. Main Outcome Measure(s): The proportion and coefficients of variation (CVs) of normal sperm, defects of specific parts, and the categories of defects were measured. The degree of agreement between any two of the three evaluators was calculated. The multiple anomalies index, teratozoospermia index, sperm deformity index, and the CVs were also measured. Result(s): The CVs of normal sperm, multiple anomalies index, teratozoospermia index, and sperm deformity index were 4.80%, 4.14%, 5.75%, and 6.81%, respectively. A broader range (4.80%–132.97%) of CVs was observed for the recognition of various defects. The coefficients of the degree of agreement concerning specific morphologic parts of sperm varied (0.387–0.607), with lower relative values for the head and mid-piece than for the tail and cytoplasm. Conclusion(s): The sperm head is more difficult to evaluate than the other parts using the criteria recommended by the World Health Organization in 2010. The degree of agreement concerning specific parts and various defects varied in broad ranges. A stricter definition for each defect is needed. [ABSTRACT FROM AUTHOR]