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Traumatic brain injury (TBI), especially moderate or severe TBI, is one of the most devastating injuries to the nervous system, as the existing therapies for neurological defect repair have difficulty achieving satisfactory results. Neural stem cells (NSCs) therapy is a potentially effective treatment option, especially after specific genetic modifications and when used in combination with biomimetic biological scaffolds. In this study, tussah silk fibroin (TSF) scaffolds with interconnected nanofibrous structures were fabricated using a top-down method. We constructed the apelin-overexpressing NSCs that were cocultured with a TSF nanofiber scaffold (TSFNS) that simulated the extracellular matrix in vitro. To verify the therapeutic efficacy of engineered NSCs in vivo, we constructed TBI models and randomized the C57BL/6 mice into three groups: a control group, an NSC-ctrl group (transplantation of NSCs integrated on TSFNS), and an NSC-apelin group (transplantation of apelin-overexpressing NSCs integrated on TSFNS). The neurological functions of the model mice were evaluated in stages. Specimens were obtained 24 days after transplantation for immunohistochemistry, immunofluorescence, and western blot experiments, and statistical analysis was performed. The results showed that the combination of the TSFNS and apelin overexpression guided extension and elevated the proliferation and differentiation of NSCs both in vivo and in vitro. Moreover, the transplantation of TSFNS-NSCs-Apelin reduced lesion volume, enhanced angiogenesis, inhibited neuronal apoptosis, reduced blood-brain barrier damage, and mitigated neuroinflammation. In summary, TSFNS-NSC-Apelin therapy could build a microenvironment that is more conducive to neural repair to promote the recovery of injured neurological function. [ABSTRACT FROM AUTHOR]

Due to the growing industry and industrialization of many urban communities, one of the dangers that threaten human life is long‐term exposure to heavy metals such as lead. Lead contamination can have a detrimental effect on fertility. On the other hand, the combination of ginger and zinc supplements can be a powerful sexual enhancer. Despite extensive studies on the effect of ginger and zinc on reproduction, the effects of the combination of ginger and zinc supplement on lead‐induced reproductive dysfunction are not fully understood. Sixty‐four adult male rats were allocated into control, lead acetate (10 mg/kg), ginger (250 mg/kg), ginger–lead group, zinc (120 mg/kg) group, zinc–lead group, ginger–zinc group and ginger–zinc–lead group. The drugs were administrated by gavage for 4 weeks. The concentration of LH, FSH, testosterone, TNF‐α, IL‐1β, antioxidant enzyme activity, MDA, spermatogenesis, and sperm parameters were measured. The expression of NF‐kB, Nrf2, Bcl2, BAX, and Cas‐3 was evaluated. The histopathological assessment was also detected. Lead significantly could induce inflammation, apoptosis, and oxidative damage in testis tissue, and decrease hormonal levels, spermatogenesis, and sperm parameters compared to the control group (p < 0.05). While in reverse manner ginger, zinc, and their combination significantly improved all of them compared to the lead group (p < 0.05). These results were also supported by histological findings. It can be concluded that ginger, zinc, and their combination could prevent lead‐induced reproductive dysfunction by inhibiting apoptosis mediated by oxidative damage and inflammation and improve reproductive performance. [ABSTRACT FROM AUTHOR]

Polystyrene nanoparticles (PS-NPs) are organic pollutants that are widely detected in the environment and organisms, posing potential threats to both ecosystems and human health. PS-NPs have been proven to penetrate the blood–brain barrier and increase the incidence of neurodegenerative diseases. However, information relating to the pathogenic molecular mechanism is still unclear. This study investigated the neurotoxicity and regulatory mechanisms of PS-NPs in human neuroblastoma SHSY-5Y cells. The results show that PS-NPs caused obvious mitochondrial damages, as evidenced by inhibited cell proliferation, increased lactate dehydrogenase release, stimulated oxidative stress responses, elevated Ca2+ level and apoptosis, and reduced mitochondrial membrane potential and adenosine triphosphate levels. The increased release of cytochrome c and the overexpression of apoptosis-related proteins apoptotic protease activating factor-1 (Apaf-1), cysteinyl aspartate specific proteinase-3 (caspase-3), and caspase-9 indicate the activation of the mitochondrial apoptosis pathway. In addition, the upregulation of autophagy markers light chain 3-II (LC3-II), Beclin-1, and autophagy-related protein (Atg) 5/12/16L suggests that PS-NPs could promote autophagy in SHSY-5Y cells. The RNA interference of Beclin-1 confirms the regulatory role of autophagy in PS-NP-induced neurotoxicity. The administration of antioxidant N-acetylcysteine (NAC) significantly attenuated the cytotoxicity and autophagy activation induced by PS-NP exposure. Generally, PS-NPs could induce neurotoxicity in SHSY-5Y cells via autophagy activation and mitochondria dysfunction, which was modulated by mitochondrial oxidative stress. Mitochondrial damages caused by oxidative stress could potentially be involved in the pathological mechanisms for PS-NP-induced neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Background: Although ongoing development of therapeutic strategies contributes to the improvements in clinical management, clear cell renal cell carcinoma (ccRCC) deaths originate mainly from radiochemoresistant and metastatic disease. Transcription factor SALL4 has been implicated in tumorigenesis and metastasis of multiple cancers. However, it is not known whether SALL4 is involved in the pathogenesis of ccRCC. Methods: Analyses of clinical specimen and publicly available datasets were performed to determine the expression level and clinical significance of SALL4 in ccRCC. The influence of SALL4 expression on ccRCC tumor growth, metastasis and vascularity was evaluated through a series of in vitro and in vivo experiments. Western blotting, immunofluorescence staining and integrative database analysis were carried out to investigate the underlying mechanism for SALL4-mediated oncogenic activities in ccRCC. Results: SALL4 expression was increased in ccRCC and positively correlated with tumor progression and poor prognosis. SALL4 could promote ccRCC cell proliferation, colony formation, cell cycle progression, migration, invasion and tumorigenicity and inhibit cell senescence. Further investigation revealed a widespread association of SALL4 with individual gene transcription and the involvement of SALL4 in endothelium development and vasculogenesis. In the context of ccRCC, SALL4 promoted tumor vascularization by recruiting endothelial cells. In addition, we found that SALL4 could exert its tumor-promoting effect via modulating Akt/GSK-3β axis and VEGFA expression. VHL mutation and DNA hypomethylation may be involved in the upregulation of SALL4 in ccRCC. Conclusions: Overall, our results provide evidence that upregulated SALL4 can function as a crucial regulator of tumor pathogenesis and progression in ccRCC, thus offering potential therapeutic strategies for future treatment. [ABSTRACT FROM AUTHOR]

This article explores the impact mechanism of different types of environmental regulations on corporate green technology innovation (GTI). The research focuses on analyzing three types of environmental regulations: command based environmental regulation (ER1), market-oriented environmental regulation (ER2), and voluntary environmental regulation (ER3), and how they affect corporate GTI. This study selected enterprise GTI as the dependent variable and measured it by the number of applications for green invention patents and green utility model patents. The independent variables are the three types of environmental regulations mentioned above. According to data from Chinese A-share listed companies. Using benchmark regression models to analyze the impact of different environmental regulations on GTI, and constructing a moderating effect model to study the role of corporate R&D investment and government support in the process of environmental regulations affecting GTI. The results indicate that (1) ER1, ER2, and ER3 can all promote enterprise GTI, and the three environmental regulatory methods have a better synergistic effect. (2) R&D investment has a positive correlation with the relationship between ER2 and GTI, and a negative correlation with ER 3 and ER 1. (3) There are differences in the GTI performance of enterprises in different regions, ownership nature, factor density, and industry types under the influence of environmental regulations. (4) The impact of environmental regulatory policies on corporate GTI is mainly short-term. This study provides a new perspective on how environmental regulations affect corporate GTI, especially in the context of developing countries like China. The research findings emphasize the role of different types of environmental regulations in incentivizing corporate GTI, while also pointing out factors that governments need to consider when formulating environmental policies, such as regional differences and corporate characteristics, which are of great significance for promoting green development of enterprises and achieving broader sustainable development goals. [ABSTRACT FROM AUTHOR]

With rapid economic expansion, China is faced with environmental challenges like air pollution and greenhouse gas emissions. Shifting from conventional fossil fuels to renewable energy (REN) sources is critical to facilitate sustainable development in China. Compared to coal and oil, REN such as solar and wind energy emit less carbon emissions. Fostering innovation of REN technologies is thus essential for China's green transition. This study aims to analyze the impact of REN technology innovation on China's economic growth using panel data models. The results demonstrate that advancing REN technologies significantly promotes GDP increase in China. Targeted policy incentives must be implemented to accelerate REN technology progression and adoption across the country. Transitioning towards REN systems will be instrumental for China to achieve environmental sustainability while maintaining economic growth. [ABSTRACT FROM AUTHOR]

Simple Summary: Chub mackerel is an economic fishery species that is key in transferring energy from zooplankton to large-bodied carnivores through the local food webs. Understanding the ecological conversion efficiency of this species is important for ecosystem-based fishery. However, the ecological conversion efficiency cannot be accurately determined in the laboratory. In this study, an in situ enrichment method was designed to simulate the wild conditions and used for the determination of ecological conversion efficiency of chub mackerel. Additionally, the method described in this study provided insights into the determination of other wild fishes that are difficult to sample in situ and domesticate in the laboratory. Understanding the ecological conversion efficiency of a fish species can be used to estimate the potential impact of the marine food web and accordingly provides scientific advice to ecosystem-based fishery management. However, only laboratory experiments may limit the accuracy of determining this index. In this study, food ingestion and ecological conversion efficiency of wild chub mackerel (Somber japonicus), a typical marine pelagic fish, were determined with gastric evacuation method in laboratory and in situ enriched simulation conditions. Additionally, the effect of temperature and body weight on ecological conversion efficiency was further estimated based on the 2D interpolation method. The results showed that, at 25.1 °C, the ecological conversion efficiency determined in-lab (35.31%) was significantly higher than in situ (23.85%). Moreover, the interpolation model estimated that with an increase in temperature (10–27 °C), the ecological conversion efficiency initially decreased, followed by an increase when the temperature reached 18 °C, but the ecological conversion efficiency generally decreased against the body weight at each temperature. The findings of this study enhanced the understanding of the energy budget of chub mackerel and also provided an efficient method for the determination of wild fishes that are difficult to sample in situ and domesticate in the laboratory. [ABSTRACT FROM AUTHOR]

In contrast to the released/circulating membrane vesicles (extracellular vesicles), cell-bound membrane vesicles are poorly identified and characterized. In this study, cell-bound membrane vesicles on human umbilical vein endothelial cells (HUVECs) and human hepatoma HepG-2 cells were investigated. We identified that cell-bound membrane vesicles are not co-localized with the major markers for extracellular vesicles (e.g. phosphatidylserine, CD63, CD107α, CD31, and DNA fragments for the three well-known types of extracellular vesicles) and for intracellular organelles with similar sizes (e.g. MitoTracker and LAMP1/LAMP3 for mitochondria and multivesicular bodies or lysosomes, respectively). The data imply that cell-bound membrane vesicles are neither the precursors of extracellular vesicles nor a false structure pushed up by an intracellular organelle but probably a novel unknown structure in the plasma membrane. Moreover, we revealed that cell-bound membrane vesicles are resistant to various detergents including but probably not limited to Triton X-100, SDS, and saponin. We further characterized that these unique vesicles are soluble in organic solvents (e.g. chloroform-methanol mixture and ethanol) which can be prevented by a lipid-stabilizing fixative (e.g. OsO 4 ) and that they are co-localized with, but do not monopolize, the major markers (e.g. caveolin-1 and GM1) for lipid rafts (a nano-sized detergent-resistant domains in the plasma membrane). The data imply that cell-bound membrane vesicles contain the lipid component and lipid rafts. Involvement of other specific unknown components might explain the detergent resistance of cell-bound membrane vesicles. Further research will mainly depend on the establishment of an effective approach for isolation/purification of these vesicles from the plasma membrane. [ABSTRACT FROM AUTHOR]

While circulating/plasma membrane vesicles have been extensively characterized, due to the lack of effective methods cell-bound membrane vesicles are poorly understood including their shape and correlation with the intracellular cytoskeleton. In this study, we focused on cell-bound membrane vesicles and individual vesicle-derived pits on endothelial cells by using confocal microscopy and atomic force microscopy (AFM). For the first time, we found that cell-bound membrane vesicles are hemisphere-shaped and that the actin cortical filaments/network lies at the cytosolic opening of a vesicle instead of being closely attached to the inner side of the vesicle membrane. This structure of cell-bound membrane vesicles may be beneficial to their movement in, or release from, the plasma membrane of cells due to less membrane–cytoskeleton coupling to be broken therefore probably minimizing energy consumption and time usage. Further study indicates that TNF-α activation induced a significant increase in average number/size of cell-bound vesicles and the local disruption of the actin network at the cytosolic opening of cell-bound vesicles. [ABSTRACT FROM AUTHOR]

Biomaterial and regenerative medical research has diversified and developed rapidly. A biological scaffold consisting of an extracellular matrix (ECM) functions not only as a supportive material but also as a regulator of cellular functions. Although decellularized scaffolds have been widely applied for the repair of non-central nervous system (CNS) tissues, their efficacy in the CNS has not been extensively investigated. In this report, we describe a dynamic decellularization protocol that combined intracardial perfusion and a series of treatments to effectively remove the cellular components from the cerebellum, which is a unique and relatively simple CNS structure. The resulting cerebellar scaffold retained neurosupportive proteins and growth factors and, when tested with neural stem cells (NSCs) in vitro, was found to be cytocompatible and to stimulate the proliferation and migration of these cells. NSCs that were cultured in vitro on the scaffold differentiated into neurons and astrocytes, as indicated by their expression of βIII-tubulin and glial fibrillary acidic protein (GFAP). Through subcutaneous and intracranial implantation experiments, this preliminary study demonstrated the in vivo biocompatibility of the cerebellar scaffold and indicated its potential for future applications. Thus, our study demonstrated that the cerebellar ECM scaffold provided tissue-specific advantages for regenerative medical applications. [ABSTRACT FROM AUTHOR]

Abstract: The ecological conversion efficiencies in twelve species of fish in the Yellow Sea Ecosystem, i.e., anchovy (Engraulis japonicus), rednose anchovy (Thrissa kammalensis), chub mackerel (Scomber japonicus), halfbeak (Hyporhamphus sajori), gizzard shad (Konosirus punctatus), sand lance (Ammodytes personatus), red seabream (Pagrus major), black porgy (Acanthopagrus schlegeli), black rockfish (Sebastes schlegeli), finespot goby (Chaeturichthys stigmatias), tiger puffer (Takifugu rubripes), and fat greenling (Hexagrammos otakii), were estimated through experiments conducted either in situ or in a laboratory. The ecological conversion efficiencies were significantly different among these species. As indicated, the food conversion efficiencies and the energy conversion efficiencies varied from 12.9% to 42.1% and from 12.7% to 43.0%, respectively. Water temperature and ration level are the main factors influencing the ecological conversion efficiencies of marine fish. The higher conversion efficiency of a given species in a natural ecosystem is acquired only under the moderate environment conditions. A negative relationship between ecological conversion efficiency and trophic level among ten species was observed. Such a relationship indicates that the ecological efficiency in the upper trophic levels would increase after fishing down marine food web in the Yellow Sea ecosystem. [Copyright &y& Elsevier]

Objectives: As a few types of glioma, young high-risk low-grade gliomas (HRLGGs) have higher requirements for postoperative quality of life. Although adjuvant chemotherapy with delayed radiotherapy is the first treatment strategy for HRLGGs, not all HRLGGs benefit from it. Accurate assessment of chemosensitivity in HRLGGs is vital for making treatment choices. This study developed a multimodal fusion radiomics (MFR) model to support radiochemotherapy decision-making for HRLGGs. Methods: A MFR model combining macroscopic MRI and microscopic pathological images was proposed. Multiscale features including macroscopic tumor structure and microscopic histological layer and nuclear information were grabbed by unique paradigm, respectively. Then, these features were adaptively incorporated into the MFR model through attention mechanism to predict the chemosensitivity of temozolomide (TMZ) by means of objective response rate and progression free survival (PFS). Results: Macroscopic tumor texture complexity and microscopic nuclear size showed significant statistical differences (p < 0.001) between sensitivity and insensitivity groups. The MFR model achieved stable prediction results, with an area under the curve of 0.950 (95% CI: 0.942–0.958), sensitivity of 0.833 (95% CI: 0.780–0.848), specificity of 0.929 (95% CI: 0.914–0.936), positive predictive value of 0.833 (95% CI: 0.811–0.860), and negative predictive value of 0.929 (95% CI: 0.914–0.934). The predictive efficacy of MFR was significantly higher than that of the reported molecular markers (p < 0.001). MFR was also demonstrated to be a predictor of PFS. Conclusions: A MFR model including radiomics and pathological features predicts accurately the response postoperative TMZ treatment. Clinical relevance statement: Our MFR model could identify young high-risk low-grade glioma patients who can have the most benefit from postoperative upfront temozolomide (TMZ) treatment. Key Points: • Multimodal radiomics is proposed to support the radiochemotherapy of glioma. • Some macro and micro image markers related to tumor chemotherapy sensitivity are revealed. • The proposed model surpasses reported molecular markers, with a promising area under the curve (AUC) of 0.95. [ABSTRACT FROM AUTHOR]

Background: Intracerebral hemorrhage (ICH) is a devastating neurological disease causing severe sensorimotor dysfunction and cognitive decline, yet there is no effective treatment strategy to alleviate outcomes of these patients. The Mas axis-mediated neuroprotection is involved in the pathology of various neurological diseases, however, the role of the Mas receptor in the setting of ICH remains to be elucidated. Methods: C57BL/6 mice were used to establish the ICH model by injection of collagenase into mice striatum. The Mas receptor agonist AVE0991 was administered intranasally (0.9 mg/kg) after ICH. Using a combination of behavioral tests, Western blots, immunofluorescence staining, hematoma volume, brain edema, quantitative-PCR, TUNEL staining, Fluoro-Jade C staining, Nissl staining, and pharmacological methods, we examined the impact of intranasal application of AVE0991 on hematoma absorption and neurological outcomes following ICH and investigated the underlying mechanism. Results: Mas receptor was found to be significantly expressed in activated microglia/macrophages, and the peak expression of Mas receptor in microglia/macrophages was observed at approximately 3–5 days, followed by a subsequent decline. Activation of Mas by AVE0991 post-treatment promoted hematoma absorption, reduced brain edema, and improved both short- and long-term neurological functions in ICH mice. Moreover, AVE0991 treatment effectively attenuated neuronal apoptosis, inhibited neutrophil infiltration, and reduced the release of inflammatory cytokines in perihematomal areas after ICH. Mechanistically, AVE0991 post-treatment significantly promoted the transformation of microglia/macrophages towards an anti-inflammatory, phagocytic, and reparative phenotype, and this functional phenotypic transition of microglia/macrophages by Mas activation was abolished by both Mas inhibitor A779 and Nrf2 inhibitor ML385. Furthermore, hematoma clearance and neuroprotective effects of AVE0991 treatment were reversed after microglia depletion in ICH. Conclusions: Mas activation can promote hematoma absorption, ameliorate neurological deficits, alleviate neuron apoptosis, reduced neuroinflammation, and regulate the function and phenotype of microglia/macrophages via Akt/Nrf2 signaling pathway after ICH. Thus, intranasal application of Mas agonist ACE0991 may provide promising strategy for clinical treatment of ICH patients. [ABSTRACT FROM AUTHOR]

The diagnostic value of audiovisual sexual stimulation (AVSS) for psychogenic erectile dysfunction (ED) is still unclear. We investigated the independent diagnostic value and optimal cut-off parameter of AVSS for psychogenic ED. All participants had received the AVSS test and nocturnal penile tumescence and rigidity (NPTR) monitoring at least twice. ED patients were divided into psychogenic ED and organic ED according to NPTR examination. The diagnostic accuracy of AVSS parameters was evaluated with the receiver operating characteristic (ROC) curve, and the Youden index was employed to determine the optimal diagnostic cut-off values. A total of 346 patients with ED and 60 healthy men were included in this study, among which 162 and 184 cases of psychogenic and organic ED were identified based on NPTR, respectively. When comparing the two ED groups, the area under the curve (AUC) of AVSS parameters was 0.85–0.89. Six-selected AVSS parameters could precisely diagnose psychogenic ED, exhibiting increased diagnostic specificity compared with corresponding sensitivity. When comparing psychogenic ED with the control group, the AUC of the tumescence of the tip was superior to the AUC other parameters (0.81 vs. 0.58, 0.66, 0.59, 0.53, 0.68), and the best determined diagnostic cut-off value was the tumescence of the tip < 29.87%. Independent AVSS could diagnose psychogenic ED objectively and effectively, and its diagnostic value was highest when 1.50% ≤ tumescence of the tip < 29.87%. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is one of the most serious public health concerns facing the world. Its characteristic feature is neuroinflammation due to microglial activation. Electroacupuncture is one of the therapies employed to improve the condition of patients with AD, although its mechanism of action is still to be determined. Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglia-specific receptor that is involved in regulating neuroinflammation in AD. In this study, we applied senescence-accelerated mouse-prone 8 mice as the AD animal model, used the Morris water maze, and applied hematoxylin and eosin staining, immunofluorescence double staining, and Western blotting, to explore the effects and potential mechanisms of action of electroacupuncture. In summary, this study suggested that electroacupuncture treatment could improve the learning and memory abilities (p < 0.05) and protect neurons. These effects result from acupuncture could upregulate TREM2 expression in the hippocampus (p < 0.01), which was essential for the anti-inflammatory effects in the AD animal model. However, further studies are needed to conclusively demonstrate the mechanism of action of electroacupuncture in AD. [ABSTRACT FROM AUTHOR]

A qualitative understanding of the long‐term variation in the population dynamics of Yellow Sea (YS) herring is particularly important for clarifying the evolutionary processes and driving mechanisms of the YS large marine ecosystem. Unfortunately, because of a lack of long‐term, continuous, and simultaneous monitoring data, the specific driving processes and mechanisms of climate effects on the population dynamics of YS herring remain largely unknown. In response to this scientific issue, we preliminarily propose the idea of reconstructing long‐term changes in YS herring abundance over the past 590 years (AD 1417–2004) based on historical documents and attempt to explore the impacts of climate on the population. Our results show that YS herring abundance maintained at a relatively high level from AD 1417 to 1870 (during the Little Ice Age); in contrast, the population declined significantly from AD 1870 to 2004 at different rates. In addition, we also found that there were strong relationships between the population abundance of YS herring and the Pacific decadal oscillation (PDO) and drought/flood cycles. We suggest that the fluctuations in YS herring abundance may be influenced by ocean–climatic circulation shifts throughout the North Pacific, especially the PDO. [ABSTRACT FROM AUTHOR]

This paper summarizes the changing states of the food resources in the Yellow Sea Large Marine Ecosystem under multiple stressors from 1958 to 2015, including the changing states of biomass yields, species composition, trophic level and biodiversity. The results show that the changing trends were contrary to expectation. There were no significant declines in biomass yields, trophic level and biodiversity after the 1980s. The major decline observed occurred before the 1980s. However, the species composition changed a lot, that is, over the past half century there were two different types of species shift in YSLME under multiple stresses. One was from demersal, high value species to pelagic, lower value species shift during 1958–59 to 1998–2000, and the other was from pelagic, lower value species to demersal, low value species shift during 1998–2000–2014-15. For future sustainable development, it is still necessary to further strengthen adaptive management. [ABSTRACT FROM AUTHOR]

MicroRNA-543 (miR-543) has been suggested as an important regulator of the development and progression of various cancer types. However, the role and biological function of miR-543 in clear cell renal cell carcinoma (ccRCC) remains unclear. Here, we found that miR-543 expression was significantly increased in tumor tissues from ccRCC patients and ccRCC cell lines. We found that overexpression of miR-543 markedly promoted the proliferation and invasion of ccRCC cells, whereas suppression of miR-543 had the opposite effects. Krüppel-like factor 6 (KLF6) was identified as a target gene of miR-543. Furthermore, we found that miR-543 negatively regulates the expression of KLF6 and p21 in ccRCC cells. Overexpression of KLF6 markedly attenuated the oncogenic effect of miR-543 overexpression. Moreover, knockdown of KLF6 significantly reversed the antitumor effect of miR-543 inhibition. Overall, our results demonstrate that miR-543 promotes the proliferation and invasion of ccRCC cells by targeting KLF6 and suggest that miR-543 may serve as a potential therapeutic target for treatment of ccRCC. [ABSTRACT FROM AUTHOR]

Engineered extracellular vesicles (EVs) are considered excellent delivery vehicles for a variety of therapeutic agents, including nucleic acids, proteins, drugs, and nanomaterials. Recently, several studies have indicated that clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated 9 (Cas9) delivered by EVs enable efficient DNA editing. However, an RNA editing tool delivered by EVs is still unavailable. Here, a signal peptide‐optimized and EVs‐delivered guide RNA (gRNA) and CRISPR/CasRx (Cas13d) system capable of rapidly inhibiting the expression of targeted genes with quick catabolism after performing their functions is developed. EVs with CRISPR/CasRx and tandem gRNAs targeting pivotal cytokines are further packed whose levels increase substantially over the course of acute inflammatory diseases and find that these engineered EVs inhibit macrophage activation in vitro. More importantly, this system attenuates lipopolysaccharide (LPS)‐triggered acute lung injury and sepsis in the acute phase, mitigating organ damage and improving the prognosis in vivo. In summary, a potent tool is provided for short‐acting RNA editing, which could be a powerful therapeutic platform for the treatment of acute diseases. [ABSTRACT FROM AUTHOR]

Fewer than 5 % glioblastoma (GBM) patients survive over five years and are termed long-term survivors (LTS), yet their molecular background is unclear. The present cohort included 72 isocitrate dehydrogenase (IDH)-wildtype GBM patients, consisting of 35 LTS and 37 short-term survivors (STS), and we employed whole exome sequencing, RNA-seq and DNA methylation array to delineate this largest LTS cohort to date. Although LTS and STS demonstrated analogous clinical characters and classical GBM biomarkers, CASC5 (P = 0.002) and SPEN (P = 0.013) mutations were enriched in LTS, whereas gene-to-gene fusions were concentrated in STS (P = 0.007). Importantly, LTS exhibited higher tumor mutation burden (P < 0.001) and copy number (CN) increase (P = 0.013), but lower mutant-allele tumor heterogeneity score (P < 0.001) and CN decrease (P = 0.026). Additionally, LTS demonstrated hypermethylated genome (P < 0.001) relative to STS. Differentially expressed and methylated genes both enriched in olfactory transduction. Further, analysis of the tumor microenvironment revealed higher infiltration of M1 macrophages (P = 0.043), B cells (P = 0.016), class-switched memory B cells (P = 0.002), central memory CD4+ T cells (P = 0.031) and CD4+ Th1 cells (P = 0.005) in LTS. We also separately analyzed a subset of patients who were methylation class-defined GBM, contributing 70.8 % of the entire cohort, and obtained similar results relative to prior analyses. Finally, we demonstrated that LTS and STS could be distinguished using a subset of molecular features. Taken together, the present study delineated unique molecular attributes of LTS GBM. • LTS were characterized by hypermethylated genome, copy number increase and higher TMB. • LTS demonstrated distinct TME and olfactory transduction-related pathway enrichment. • STS showed heterogeneous tumor tissue, more gene fusion and copy number decrease. • Most LTS and STS were confirmed as methylation class-defined GBM (m-GBM). • The molecular features of m-GBM patients were in accordance with the entire cohort. [ABSTRACT FROM AUTHOR]

Background: Cell-bound membrane vesicles (CBMVs) are a type of membrane vesicles different from the well-known extracellular vesicles (EVs). In recent years, the applications of EVs as drug delivery systems have been studied widely. A question may arise whether isolated CBMVs also have the possibility of being recruited as a drug delivery system or nanocarrier? Methods: To test the possibility, CBMVs were isolated/purified from the surfaces of cultured endothelial cells, loaded with a putative antitumor drug doxorubicin (Dox), and characterized. Subsequently, cellular experiments and animal experiments using mouse models were performed to determine the in vitro and in vivo antitumor effects of Dox-loaded CBMVs (Dox-CBMVs or Dox@CBMVs), respectively. Results: Both Dox-free and Dox-loaded CBMVs were globular-shaped and nanometer-sized with an average diameter of ~ 300–400 nm. Dox-CBMVs could be internalized by cells and could kill multiple types of cancer cells. The in vivo antitumor ability of Dox-CBMVs also was confirmed. Moreover, Quantifications of blood cells (white blood cells and platelets) and specific enzymes (aspartate aminotransferase and creatine kinase isoenzymes) showed that Dox-CBMVs had lower side effects compared with free Dox. Conclusions: The data show that the CBMV-entrapped Doxorubicin has the antitumor efficacy with lower side effects. This study provides evidence supporting the possibility of isolated cell-bound membrane vesicles as a novel drug nanocarrier. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) represents an extremely debilitating condition for which no efficacious treatment is available. Because spinal cord does not have satisfactory capacity for revascularization after injury, it seems to be a promising way to modulate the lesion environment by reperfusion to promote a regenerative phenotype. Although engineered scaffolds provide a platform to deliver therapeutic cells and neurotrophic factors, slow and insufficient vascularization of large tissue constructs negatively impacts the survival and function of these transplanted cells. In this study, we cocultured our fibrous porous silk scaffold (FPSS) with ADAMTS13-overexpressing human umbilical vein endothelial cells (HUVECs) in vitro and transplanted this prevascularized construct into an SCI mouse model. The prevascularized system exhibited a tube-like structure in vitro, promoted vascular infiltration and microvascular network formation after transplantation, and recruited more neural cells to the lesion site. Twenty-eight days later, behavioral analysis showed that locomotor recovery was significantly improved in treated animals compared with control animals. Taken together, our results suggest that the FPSS-HUVECs system promoted neovascularization, guided axon growth at the injury site, and improved the microenvironment. Therefore, this prevascularization system may provide a better therapeutic option for SCI. [ABSTRACT FROM AUTHOR]

Giant cell glioblastoma (gcGBM) is a rare histological variant of GBM, accounting for about 1% of all GBM. The prognosis is poor generally though gcGBM does slightly better than the other IDH‐wild‐type GBM. Because of the rarity of the cases, there has been no comprehensive molecular analysis of gcGBM. Previously, single‐gene study identified genetic changes in TP53, PTEN and TERT promoter mutation in gcGBM. In this report, we performed whole‐exome sequencing (WES) to identify somatically acquired mutations and copy number variations (CNVs) in 10 gcGBM genomes. We also examined TERT promoter mutation and MGMT methylation in our cohort. On top of the reported mutations, WES revealed ATRX, PIK3R1, RB1 and SETD2 as the recurrent mutations in gcGBM. Notably, one tumor harbored a mutation in MutS homolog 6 (MSH6) that is a key mismatch repair (MMR) gene. This tumor demonstrated hypermutation phenotype and showed an increased number of somatic mutations. TERT promoter mutation and MGMT methylation were observed in 20% and 40% of our samples, respectively. In conclusion, we described relevant mutation profiling for developing future targeted therapies in gcGBM. [ABSTRACT FROM AUTHOR]

Oxidative stress is considered as major culprit for neurodegenerative diseases and triggers cognitive and memory impairments. The present study mainly aimed to study the protective effects and underlying mechanisms of aloin on d -galactose (d -gal) induced ageing mice. Our results demonstrated that chronic administration of d -gal (150 mg kg−1) in mice caused spontaneous and cognitive impairments, as determined by open-field test and Morris water-maze test. Aloin treatment significantly ameliorated histopathological damage, attenuated the microglia activation and reduced levels of inflammatory mediators, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6 in the hippocampus. Moreover, it effectively suppressed the level of reactive oxygen species (ROS) and increased antioxidant enzymes activities. Further data showed that these protective effects were accompanied by inhibition of the activation of nuclear factor kappa B and the phosphorylation of p38 and ERK. In conclusion, the present study suggests that aloin can ameliorate d -gal induced oxidative stress, cognitive impairment and inflammation, possibly via mediating the ERK, p38 and NF-κB signaling pathways. • Aloin ameliorates d -gal induced spontaneous and cognitive impairments. • Aloin ameliorates d -gal induced oxidative stress and inflammation in brain of d -gal induced mice. • Aloin inhibited ERK, p38 and NF-κB signal in brain of d -gal induced mice. [ABSTRACT FROM AUTHOR]

• New designed poly (β amino esters) (PBAE) nano-platform can achieve mRNA delivery to brain and spinal cord efficiently. • Stable mRNA secondary structures were engineered by AI and contributed to higher protein expressions. • 3′UTR of mRNA was engineered to achieve neuron selective delivery with less side effects. Brain-derived neurotrophic factor (BDNF) has a long history in the treatment neurodegenerative of diseases. However, this therapy has limitations in exogenous protein safety, including side effects like neuropathic pain and seizures. Moreover, there are currently no positive clinical trial results using BDNF-based gene therapy. Given this, new methods of delivering BDNF are urgently needed. Here, we report an engineering BDNF mRNA-based therapy in a murine model of Alzheimer's disease (AD). Two poly (β amino esters) polymers (PBAE) were synthesized, which achieved mRNA delivery to brain and spinal cord efficiently following catheter ventricle pumping. To confer stability and RNase resistance, the secondary structure of the mRNA was engineering using AI algorithms. Further mRNA modification was done on 3′ untranslated region (3′UTR), which was added with neuron-specific miRNA targeting sequence to avoid BDNF protein expression in neuron. This allowed reduced neuronal overexcitation and seizures. And BDNF protein was sustained released from astrocytes to maintain surrounding neural function. The engineering mRNA was delivered into the brain ventricle and translated into astrocytes to significantly improve the memory of AD mice. Given the mRNA modifications presented here, it would de-target delivery to specific cell types and has therapeutic potential for the treatment of neurological diseases. [ABSTRACT FROM AUTHOR]

Background: The size and receptor-binding abilities of plasma lipoproteins are closely related with their structure/functions. Presently, the sizes of native lipoproteins have been measured by various methods including atomic force microscopy (AFM) whereas the sizes of modified lipoproteins are poorly determined and the receptor-binding ability of lipoproteins is less detected and compared at the nanoscale. Methods: Here, AFM was utilized to detect/compare the size and scavenger receptor-binding properties of three native human lipoproteins including high-density lipoprotein, low-density lipoprotein (LDL), and very low-density lipoprotein, and two modified human lipoproteins including oxidized and acetylated LDL, as well as bovine serum albumin and their antibodies as negative and positive controls, respectively. Results: AFM detected that the sizes of these lipoproteins are close to the commonly known values and the previously-reported AFM-detected sizes and that native and modified LDL have different height/size. AFM also revealed that the CD36-binding abilities of the five lipoproteins are different from one another and from their SR-B1-binding abilities and that the anti-CD36/SR-B1 antibodies as positive controls have strong CD36/SR-B1-binding abilities. Conclusions: The data provide important information on lipoproteins for better understanding their structures/functions. Moreover, the data certify that besides size measurement AFM also can visualize receptor-lipoprotein binding at the nanoscale, as well as antigen–antibody (scavenger receptors and their antibodies) binding. [ABSTRACT FROM AUTHOR]

Background: Tumor location served as an important prognostic factor in glioma patients was considered to postulate molecular features according to cell origin theory. However, anatomic distribution of unique molecular subtypes was not widely investigated. The relationship between molecular phenotype and histological subgroup were also vague based on tumor location. Our group focuses on the study of glioma anatomic location of distinctive molecular subgroups and histology subtypes, and explores the possibility of their consistency based on clinical background.Methods: We retrospectively reviewed 143 cases with both molecular information (IDH1/TERT/1p19q) and MRI images diagnosed as cerebral diffuse gliomas. The anatomic distribution was analyzed between distinctive molecular subgroups and its relationship with histological subtypes. The influence of tumor location, molecular stratification and histology diagnosis on survival outcome was investigated as well.Results: Anatomic locations of cerebral diffuse glioma indicate varied clinical outcome. Based on that, it can be stratified into five principal molecular subgroups according to IDH1/TERT/1p19q status. Triple-positive (IDH1 and TERT mutation with 1p19q codeletion) glioma tended to be oligodendroglioma present with much better clinical outcome compared to TERT mutation only group who is glioblastoma inclined (median overall survival 39 months VS 18 months). Five molecular subgroups were demonstrated with distinctive locational distribution. This kind of anatomic feature is consistent with its corresponding histological subtypes.Discussion: Each molecular subgroup in glioma has unique anatomic location which indicates distinctive clinical outcome. Molecular diagnosis can be served as perfect complementary tool for the precise diagnosis. Integration of histomolecular diagnosis will be much more helpful in routine clinical practice in the future. [ABSTRACT FROM AUTHOR]

Magnetic relaxation switches (MRS) based on target-induced state changes of magnetic nanoparticles are vital approaches for biomolecule detection in in vitro diagnosis. Recently, magnetic graphene quantum dots have been employed as magnetic probes instead of iron oxide nanoparticles and showed high sensitivity. Introducing magnetic separation into an MRS assay before the relaxometry measurements can enhance the sensitivity, elevate accuracy, and expand the linear region. In this work, magnetic separation-assisted MRS was developed to detect endoglin utilizing iron oxide as the magnetic carrier and magnetic graphene quantum dots as the magnetic probe. The assay possesses a broad linear region from 5 ng/mL to 50 μg/mL and a sensitive limit of detection of 1.3 ng/mL, which is two orders of magnitude lower than that of MRS without magnetic separation. The high accuracy and consistency have been proved for endoglin (CD105) detection in real samples. This graphene quantum dot-based MRS involving magnetic separation provides a new route for enhancing the sensitivity and accuracy of biomolecule detection. • Magnetic relaxation switch involving magnetic separation for CD105 detection. • Magnetic graphene quantum dots as magnetic probe, Fe 3 O 4 as magnetic carrier. • Enhanced sensitivity for CD105 detection with a LOD of 1.3 ng/mL. • Remarkable linear region for CD105 detection, ranging from 5 ng/mL to 50 μg/mL. • Amplified relaxation time changes lead to high accuracy and consistency. [ABSTRACT FROM AUTHOR]

The Pacific decadal oscillation (PDO) has been identified as an important driver for fluctuation of fish populations on the eastern Pacific Ocean. However, the relationship between changes in fish population and climate oscillations on a decadal time scale in the Northwest Pacific is still unclear due to the lack of reliable long-term time series data. In the present study, a time series of Engraulis japonicus (Japanese anchovy) populations was reconstructed using the density of sedimentary fish scales in the Yellow Sea basin. E . japonicus populations and the PDO index showed similar patterns on a decadal time scale. Our results confirm that climate is a major driver of ecological changes on a decadal time scale, and indicate that suitable sea water temperature might be the main forcing of anchovy migration. This work also demonstrates the potential of predicting changes in fish population based on climate records. [ABSTRACT FROM AUTHOR]

The Yellow Sea (YS) is a semi-enclosed marginal sea in the West Pacific. As part of the China GLOBEC-IMBER program, the present study set out to investigate the mechanisms involved in the seasonal patterns of phytoplankton biomass and community structure in the southern YS. During four cruises in April and October 2006, and March and August 2007, the phytoplankton spring bloom, the Yellow Sea Warm Current (YSWC) and the Yellow Sea Cold Water Mass (YSCWM) were the most remarkable biogeochemical events in the study area, involving significantly different phytoplankton communities. During cold seasons nutrient-rich water was observed, coincident with the occurrence of the YSWC, which is considered to be warm and saline water from the northward Kuroshio branch current (Cheju Warm Current). However, low Chl a concentrations (< 0.6 mg m − 3 ) and a high relative abundance of prasinophytes (29% of Chl a , average value of the euphotic zone, and the same below) were observed in the YSWC area in March. During April a spring bloom occurred with very high concentrations of Chl a (7.69 mg m − 3 ) and fucoxanthin (1.98 mg m − 3 ), and was dominated by diatoms. The mechanism and processes of the spring bloom in the central YS are very complex and possibly unique, and the YSWC affects the distribution of nutrients and hydrological environment for phytoplankton growth. Low Chl a biomass (0.2 mg m − 3 ) and a low contribution of diatoms, but a high contribution of cyanobacteria (36%) were observed in the stratified central YS in August when the YSCWM prevailed, and a high relative abundance of chrysophytes (38%) was observed in October when the YSCWM was decaying. In a word, significant seasonal variations of phytoplankton biomass and community structure were observed in the central rather than the coastal area. These results were considered as the physical–chemical–biological characteristics of the unique ecosystem in the central YS. [ABSTRACT FROM AUTHOR]

Objective: To assess the feasibility, safety, and efficiency of bilateral inguinal lymphadenectomy using simultaneous double laparoscopies for penile cancer.Materials and Methods: We reviewed retrospectively the records of 65 patients who underwent inguinal lymph nodes dissection (ILND) for penile cancer from January 2012 to May 2019. Treatments included open ILND (OILND, 19 patients), video-endoscopic inguinal lymphadenectomy (VEIL) using single laparoscopy (S-VEIL, 24 patients), and VEIL using double laparoscopies (D-VEIL, 22 patients). We evaluated the peri-operative and short-term oncological outcomes of the three groups.Results: The mean operative time of D-VEIL (105.91 ± 10.87 minutes) was significantly shorter than the other two groups, OILND shorter than S-VEIL (160.47 ± 13.74 minutes, 191.67 ± 17.80 minutes, respectively) (P < 0.001). Intraoperative blood loss in the S-VEIL and D-VEIL groups were 53.54 ± 8.78 and 48.41 ± 13.22 ml, respectively; they were significantly lower than that of the OILND group (99.74 ± 9.64 ml; P < 0.001). The numbers of unilateral and total lymph nodes harvested were similar in all groups. The complication rates in the S-VEIL group (4.2%) and the D-VEIL group (4.5%) were significantly lower than that in the OILND group (63.2%; P < 0.001). Compared with open surgery (13.53 ± 1.74 days for hospitalization; 11.37 ± 1.92 days for the left side of drain, 11.95 ± 1.84 days for the right side), the two VEIL groups had significantly shorter drainage tube residence time (7.42 ± 2.02 and 7.32 ± 1.52 days, respectively for the left side; 7.63 ± 1.81 and 7.27 ± 1.58 days, respectively for the right side), shorter postoperative hospitalization (9.46 ± 1.64 and 9.00 ± 1.83 days, respectively) (P < 0.001). There were no statistically significant differences in rates of regional recurrence and short-term survival among the three groups.Conclusion: Bilateral inguinal lymphadenectomy using double laparoscopies simultaneously can provide adequate oncological outcomes safely and efficiently, and carry significantly lower morbidity than OILND, at a median follow-up of 33.5 months. It is a more time-saving surgical approach for penile cancer patients who need bilateral ILND. [ABSTRACT FROM AUTHOR]

We assessed the function of a Patinopecten yessoensis and Saccharina japonica integrated multi-trophic aquaculture (IMTA) model on the level of organic matter produced in the environment. The study was conducted in March-July 2012 using stable carbon and nitrogen isotope methods. Results showed that the quantity of rotten kelp increased considerably over these 5 months, with the length of the rotten blades reaching 150 cm in July. The contribution rates of biodeposits by the shellfish and kelp to the suspended particulate matter (SPM) were 3.93 ± 0.39 and 4.99 ± 1.09 %, respectively, but contribution rates to the sediments in the IMTA area were very low. In May and July, rotting kelp contributed 1.06 ± 0.46 and 1.64 ± 0.13 % in the kelp area, respectively. The organic carbon and nitrogen content of sediments from the IMTA area was significantly higher than from the kelp area ( P < 0.05). C% and N% in SPM from the IMTA area were four times those from the kelp area ( P < 0.05), but the C and N content in sediments were still at a low level. [ABSTRACT FROM AUTHOR]

Direct reprogramming of human fibroblasts into functional neurons in vitro by defined factors provides an invaluable resource for regenerative medicine. However, clinical applications must consider the risk of immune rejection, thus patient-specific induced neuronal cells (iNCs) may serve as an ideal source for autologous cell replacement. In this study, we report a robust process for functional neuronal cells from the patients' scalp by lentiviral gene delivery of Ascl1, Myt1l, and Sox2. These three-factor iNCs are similar to human neuronal cells in morphology, surface antigens, gene expression, and electrophysiological characteristics. Our findings might provide a source of patient-specific functional neurons for cell therapy. [ABSTRACT FROM AUTHOR]

Direct synthesis of nanosheet Fe-ZSM-5 catalysts and their use for selective catalytic reduction (SCR) of NO by ammonia were studied. XRD, BET, SEM, EPR, and NH-TPD were used to understand the properties of catalysts with different iron loading. XRD confirmed the presence of the ZSM-5 crystal phase, and there was no FeO phase on the surface of the crystals. SEM showed the Fe-ZSM-5 catalysts comprised microspheres made up of nanosheets. EPR indicated that the iron was present as isolated Feand FeO oligomers uniformly dispersed throughout the crystals. NH-TPD indicated that Fe-ZSM-5 (20,1:1) had maximum acid sites and density at approximately 250 and 450 °C, respectively. Fe-ZSM-5 (20,1:1) had the highest activity in the SCR reaction with NH. It was also confirmed that Fe-ZSM-5 (20,1:1) had excellent resistance to SO and HO under the SCR reaction conditions. The effects of water vapor and SO, iron loading, and the Si/(Fe + Al) ratio were also investigated for these catalysts. [ABSTRACT FROM AUTHOR]

Abstract: Growth hormone (GH) is a polypeptide which is an important regulator of development and somatic growth in teleosts, and may be associated with the mechanisms which drive sexual growth dimorphism in the Half-smooth tongue sole (Cynoglossus semilaevis). In this study, the full length gh cDNA was cloned from C. semilaevis by homology cloning and the rapid amplification of cDNA ends polymerase chain reaction (RACE-PCR). The full-length gh cDNA is 826bp and contains an open reading frame (ORF) of 603bp encoding a protein of 200 amino acids (AA). The precursor of gh consists of a 17 amino-acid signal peptide followed by a 183 amino-acid mature polypeptide. GH gene sequences obtained from female and male adults consist of 3428bp and 3371bp, respectively, each of which includes six exons and five introns, and the difference in the GH gene size was mainly caused by the microsatellites. When 14 tissues from females, normal males and extra-large male adults were analyzed for sex-specific tissue expression, the gh mRNA was found to be predominantly expressed in the pituitary, and the expression levels in females were 3.6 times as much as those in normal males, while the mRNA expression in extra-large males was 1.7 times as much as those in normal males. Sex differences in gh mRNA expression during development were also examined by using a full-sib family of C. semilaevis, and the gh mRNA was detected at all of the 12 time points sampled from 10 to 380days-old. A significant increase in gh mRNA was detected starting in 80day old fish and was then followed by a drop to very low levels starting at 230day old fish. Differential expression indicated that the gh expression level in females was significantly higher than males (P <0.01) at all of the stages except for 10days-old. Two microsatellite loci were identified in the second intron of the GH gene. Using these two polymorphic markers to genotype 224 individuals, there was no significant difference between the females and males in the Bohai Sea, the Yellow Sea and the hatchery samples. [Copyright &y& Elsevier]

Abstract: Polymer-based micro/nano fluidic devices are becoming increasingly important for biological applications and fluidic control. In this paper, we propose a new method for the enclosure of the large-area channel by thermal bonding at low pressure using a flexible PET film material as bonding substrate. The flexible film allows bonding of micro/nano pattern features at such a low pressure primarily due to “sequential” bonding made possible by the mold flexibility and the conformal contact made between the bonding layer and the structure layer in large area. According to the bonding mechanism investigated using VOF simulation and experiments, high bonding temperature makes melt bonding polymer be filled into the trenches inevitably and achieve the chain entanglement of the polymer over the boundary by the capillary force. This fabrication technique has great potential for low-cost mass production of polymeric-based micro/nano fluidic devices. [Copyright &y& Elsevier]

The cytological origin of central nervous system hemangioblastoma (HB) remains unclear and controversial, largely owing to a lack of in-depth characterization of tumorigenic cells and their progeny tracking. We have now detected a cell subpopulation by stage-specific embryonic antigen-1 expression, which were defined as tumor-initiating cells (TICs) in both sporadic and familial HBs. These TICs subpopulations had universal neural stem cell characteristics. Nevertheless, the freshly sorted TICs endowed with potential of multi-progeny derivatives, including HB components and non-HB ingredients, depended on environmental induction in vitro. Importantly, the freshly harvested TICs formed malignant tumors by injection into conventional mice model, while did redevelop the characteristic HB-like structures within a special mice model with HB-microenvironment, indicating HB niche dependency for the TICs derivative specification. Taken together, the data of the present study suggested that HBs might derive from neoplastic transformation of neural stem cells/progenitors in the specific niche. [ABSTRACT FROM PUBLISHER]

Abstract: The Bohai Sea (BHS), located at the western boundary of the NW Pacific, is a shallow semienclosed sea with an area of about 77×103 km2 and average depth of 18m, surrounded by fast-developing economic zones and populous lands. Through the Bohai Strait, the BHS connects to the Yellow Sea, one of the 50 large marine ecosystems in the world ocean. The hydrographic conditions there are substantially influenced by river discharges, wind–tide–thermohaline circulation, stratification in summer, and mixing in winter. During the period of 1960–1996, temperature, salinity, dissolved inorganic nitrogen, and the N:P ratio increased from 0.005 to 0.013°C year−1, 0.04 to 0.13 year−1, 0.45 to 0.61μmolL−1 year−1, and 1.27 to 1.40year−1, respectively; while dissolved oxygen, phosphorus, silicon, and the Si:N ratio decreased from −1.59 to −2.30μmolL−1 year−1, −0.007 to −0.011μmolL−1 year−1, −0.385 to −0.602μmolL−1 year−1, and −0.064 to −0.324year−1, respectively. These changes were primarily caused by a reduced freshwater inflow. Since 1985, the concentrations of P and Si, and the Si:N ratio, have dropped to near-critical levels for diatom growth, while the N:P ratio has been below the Redfield ratio. These changes not only have had an influence on phytoplankton production, but also can decrease recruitment of the Penaeid prawn (Penaeus chinensis) and change fish community structure and diversity. [Copyright &y& Elsevier]

Abstract: Polymer-based micro/nano fluidic system is becoming indispensable for biological applications as well as physical chemistry research. In this article, we demonstrate a novel fabrication process for nano fluidic system based on hybrid mask-mould (HMM) lithography and thermal bonding using SU-8. With the HMM lithography, the protrusions of channels and reservoir patterns can be replicated in one step. Bonding process conditions are flexible and easily controllable with the use of PET substrate and the thin adhesive layer. Surface textures were found to be essential to the bonding strength and channel profile control. The fabricated fluidic system was characterized using spontaneous capillary filling with dyed water, demonstrating good quality of sealing. [Copyright &y& Elsevier]

• Shikonin ameliorates D-gal induced cognitive impairment. • Shikonin ameliorates D-gal induced oxidative stress, astrocyte activation and neuronal damage in brain of D-gal induced mice. • Shikonin inhibited MAPK and NF-κB signaling pathway in brain of D-gal induced mice. Oxidative stress acts as the major causative factor for various age‐associated neurodegenerative diseases, triggering cognitive and memory impairments. In the present study, the underlying neuroprotective mechanism governing how shikonin acts against D-galactose (D-gal)-induced memory impairment, neuroinflammation and neuron damage was examined. The results revealed that chronic administration of D-gal [150 mg/kg intraperitoneally (i.p.)] in mice caused cognitive and memory impairments, as determined by Morris water-maze test. Shikonin treatment, however, alleviated D‐gal-induced memory impairment and reversed the D‐gal-induced neural damage and apoptosis. Furthermore, western blotting and the results of morphological analysis revealed that shikonin treatments markedly reduced D‐gal induced neuroinflammation through inhibition of astrocytosis as determined by glial fibrillary acidic protein (GFAP) detection, and downregulating other inflammatory mediators, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6. Moreover, shikonin treatment led to inhibition of the activation of nuclear factor‐κB (NF‐κB) and the phosphorylation of mitogen-activated protein kinases (MAPKs), preventing neurodegeneration. Hence, taken together, the results of the present study suggested that shikonin attenuated D‐gal-induced memory impairment, neuroinflammation and neurodegeneration, possibly via the NF‐κB/mitogen-activated protein kinase (MAPK) pathway. Our data suggest that shikonin could be a promising, endogenous and compatible antioxidant candidate for age‐associated neurodegenerative diseases, including Alzheimer's disease. [ABSTRACT FROM AUTHOR]