Structural insight of cell surface sugars in viral infection and human milk glycans as natural antiviral substance.

Viral infections are caused by the adhesion of viruses to host cell receptors, including sialylated glycans, glycosaminoglycans, and human blood group antigens (HBGAs). Atomic-level structural information on the interactions between viral particles or proteins with glycans can be determined to provide precise targets for designing antiviral drugs. Milk glycans, existing as free oligosaccharides or glycoconjugates, have attracted increasing attention; milk glycans protect infants against infectious diseases, particularly poorly manageable viral infections. Furthermore, several glycans containing structurally distinct sialic acid/fucose/sulfate modifications in human milk acting as a "receptor decoy" and serving as the natural antiviral library, could interrupt virus-receptor interaction in the first line of defense for viral infection. This review highlights the basis of virus-glycan interactions, presents specific glycan receptor binding by gastroenterovirus viruses, including norovirus, enteroviruses, and the breakthroughs in the studies on the antiviral properties of human milk glycans, and also elucidates the role of glycans in respiratory viruses infection. In addition, recent advances in methods for performing virus/viral protein-glycan interactions were reported. Finally, we discuss the prospects and challenges of the studies on the clinical application of human milk glycan for viral interventions.

Characterization of Degraded Konjac Glucomannan from an Isolated Bacillus licheniformis Strain with Multi-Enzyme Synergetic Action.

The large molecular weight and high viscosity of natural konjac glucomannan (KGM) limit its industrial application. Microbial degradation of low-molecular-weight KGM has health benefits and various biological functions; however, the available KGM strains used in the industry have microbial contamination and low degradation efficiencies. Therefore, exploring novelly adaptable strains is critical for industrial processes. Here, the Bacillus licheniformis Z7-1 strain isolated from decaying konjac showed high efficiency for KGM degradation. The monosaccharide composition of the degradation products had a reduced molar ratio of mannose to glucose, indicating that Z7-1 preferentially degraded glucose in KGM. The degraded component was further characterized by ESI-MS, Fourier-transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM), and it also exhibited good antibacterial activity against various food-spoilage bacteria. Genome sequencing and zymolytic analysis revealed that abundant carbohydrate-active enzymes exist in the Z7-1 genome, with at least five types of extracellular enzymes responsible for KGM degradation, manifesting multi-enzyme synergetic action. The extracellular enzymes had significant thermal stability, indicating their potential application in industry. This study provides an alternative method for obtaining low-molecular-weight KGM with antibacterial functions and supports foundational knowledge for its development as a biocatalyst for the direct conversion of biomass polysaccharides into functional components.

Preparation of Hematoporphyrin-Poly(Lactic Acid) Nanoparticles Encapsulated Perfluoropentane/Salicylic Acid for Enhanced US/CEST MR Bimodal Imaging.

Background: Medical imaging modalities, such as magnetic resonance imaging (MRI), ultrasound, and fluorescence imaging, have gained widespread acceptance in clinical practice for tumor diagnosis. Each imaging modality has its own unique principles, advantages, and limitations, thus necessitating a multimodal approach for a comprehensive disease understanding of the disease process. To enhance diagnostic precision, physicians frequently integrate data from multiple imaging modalities, driving research advancements in multimodal imaging technology research. Methods: In this study, hematoporphyrin-poly (lactic acid) (HP-PLLA) polymer was prepared via ring-opening polymerization and thoroughly characterized using FT-IR, 1H-NMR, XRD, and TGA. HP-PLLA based nanoparticles encapsulating perfluoropentane (PFP) and salicylic acid were prepared via emulsion-solvent evaporation. Zeta potential and mean diameter were assessed using DLS and TEM. Biocompatibility was evaluated via cell migration, hemolysis, and cytotoxicity assays. Ultrasonic imaging was performed with a dedicated apparatus, while CEST MRI was conducted using a 7.0 T animal scanner. Results: We designed and prepared a novel dual-mode nanoimaging probe SA/PFP@HP-PLLA NPs. PFP enhanced US imaging, while salicylic acid bolstered CEST imaging. With an average size of 74.43 ± 1.12 nm, a polydispersity index of 0.175 ± 0.015, and a surface zeta potential of -64.1 ± 2.11 mV. These NPs exhibit excellent biocompatibility and stability. Both in vitro and in vivo experiments confirmed the SA/PFP@HP-PLLA NP's ability to improve tumor characterization and diagnostic precision. Conclusion: The SA/PFP@HP-PLLA NPs demonstrate promising dual-modality imaging capabilities, indicating their potential for preclinical and clinical use as a contrast agent.

Co-regulation of Thermosensor Pathogenic Factors by C-di-GMP-Related Two-Component Systems and a cAMP Receptor-like Protein (Clp) in Stenotrophomonas maltophilia.

Stenotrophomonas maltophilia is a major threat to the food industry and human health owing to its strong protease production and biofilm formation abilities. However, information regarding regulatory factors or potential mechanisms is limited. Herein, we observed that temperature differentially regulates biofilm formation and protease production, and a cAMP receptor-like protein (Clp) negatively regulates thermosensor biofilm formation, in contrast to protease synthesis. Among four c-di-GMP-related two-component systems (TCSs), promoter fusion analysis revealed that clp transcription levels were predominantly controlled by LotS/LotR, partially controlled by both RpfC/RpfG and a novel TCS Sm0738/Sm0737, with no obvious effect caused by Sm1912/Sm1911. Biofilm formation in Δclp and ΔTCSs strains suggested that LotS/LotR controlled biofilm formation in a Clp-mediated manner, whereas both RpfC/RpfG and Sm0738/Sm0737 may occur in a distinct pathway. Furthermore, enzymatic activity analysis combined with c-di-GMP level indicated that the enzymatic activity of c-di-GMP-related metabolism proteins may not be a vital contributor to changes in c-di-GMP level, thus influencing physiological functions. Our findings elucidate that the regulatory pathway of c-di-GMP-related TCSs and Clp in controlling spoilage or the formation of potentially pathogenic factors in Stenotrophomonas expand the understanding of c-di-GMP metabolism and provide clues to control risk factors of S. maltophilia in food safety.

Diversely regio-oxidative degradation of konjac glucomannan by lytic polysaccharide monooxygenase AA10 and generating antibacterial hydrolysate.

Konjac glucomannan (KGM) hydrolysate exhibit various biological activities and health-promoting effects. Lytic polysaccharide monooxygenases (LPMOs) play an important role on enzymatic degradation of recalcitrant polysaccharides to obtain fermentable sugars. It is generally accepted that LPMOs exhibits high substrate specificity and oxidation regioselectivity. Here, a bacteria-derived SmAA10A, with chitin-active with strict C1 oxidation, was used to catalyse KGM degradation. Through ethanol precipitation, two hydrolysed KGM components (4 kDa (KGM-1) and 5 kDa (KGM-2)) were obtained that exhibited antibacterial activity against Staphylococcus aureus. In natural KGM, KGM-1, and KGM-2, the molar ratios of mannose to glucose were 1:2.19, 1:3.05, and 1:2.87, respectively, indicating that SmAA10A preferentially degrades mannose in KGM. Fourier-transform infrared spectroscopy and scanning electron microscopy imaging revealed the breakage of glycosylic bonds during enzymatic catalysis. The regioselectivity of SmAA10A for KGM degradation was determined based on the fragmentation behaviour of the KGM-1 and KGM-2 oligosaccharides and their NaBD4-reduced forms. SmAA10A exhibited diverse oxidation degradation of KGM and generated single C1-, single C4-, and C1/C4-double oxidised oligosaccharide forms. This study provides an alternative method for obtaining KGM degradation components with antibacterial functions and expands the substrate specificity and oxidation regioselectivity of bacterial LPMOs.

Preparation and Evaluation of Folate Modified PEG-PLLA Nanoparticles Loaded with Lycorine for Glioma Treatment.

Lycorine is a kind of natural active ingredient with a strong antitumor effect. In this study, folate ligand-conjugated polyethylene glycol-block-poly(l-lactide) (PEG-PLLA) nanoparticles (FA-PEG-PLLA NPs) were designed to deliver lycorine to enhance its anti-glioma activity. The successful preparation of the FA-PEG-PLLA polymer was confirmed by 1H-NMR, FT-IR, XRD, TGA, and DSC. The optimal formulation for LYC@FA-PEG-PLLA NPs was determined by response surface analysis as follows: sodium dodecyl sulfate (SDS) of 1%, carrier material of 0.03 g, organic phase volume of 3 mL, and ultrasonic power of 20%. The LYC@FA-PEG-PLLA NPs exhibited an encapsulation efficiency of 83.58% and a particle size of 49.71 nm, demonstrating good stability. Hemolysis experiments, MTT assays, and cell scratch assays revealed excellent biocompatibility of FA-PEG-PLLA and superior anti-glioma activity of LYC@FA-PEG-PLLA NPs compared to the raw drug. Additionally, cell apoptosis assays, ROS experiments, and western blot analysis demonstrated that LYC@FA-PEG-PLLA NPs contributed to cell apoptosis by inducing ROS generation and increasing the expression of NF-κB inhibitory protein IκBα. These results suggested that LYC@FA-PEG-PLLA NPs hold promise for glioma treatment.

Ursolic acid loaded tri-block copolymer nanoparticles based on triphenylphosphine for mitochondria-targeted cancer therapy.

A novel biodegradable amphiphilic triblock copolymer, polyphosphate, polyethylene glycol, and polylactic acid (PAEEP-PEG-PLLA), was synthesized by twice ring-opening polymerization and triphenylphosphine (TPP) was grafted onto the block copolymer to synthesize a carrier material TPP-PAEEP-PEG-PLLA, which was identified by1H-nuclear magnetic resonance (1H-NMR) spectroscopy. The TPP-PAEEP-PEG-PLLA nanoparticles encapsulated with ursolic acid (UA) were prepared by the emulsion-solvent evaporation method and characterized by dynamic light scattering. The mitochondrial targeting ability of fluorescently labeled nanoparticles was evaluated by laser confocal microscopy. The average particle size and surface charge of the UA -loaded nanoparticle solution were 180.07 ± 1.67 nm and +15.57 ± 1.33 mV, respectively. The biocompatibility of nanoparticles was briefly evaluated by erythrocyte hemolysis assay.In vitrocell proliferation assay and scratch migration assay were performed to compare the difference in anti-tumor effect between UA and UA nanoparticles. The results showed that TPP-modified triblock copolymers had good mitochondrial targeting and improved the low bioavailability of UA, and UA nanoparticles exhibited more pronounced anti-tumor capabilities. In summary, the results suggested that our UA nanoparticles were a promising drug-targeted delivery system for the treatment of tumors.

Bioinformatic Identification of the Pyroptosis-Related Transcription Factor-MicroRNA-Target Gene Regulatory Network in Angiotensin II-Induced Cardiac Remodeling and Validation of Key Components.

BACKGROUND: Accumulative evidence suggests that pyroptosis plays a key role in mediating angiotensin II (Ang II)-induced cardiac remodeling However, the potential role of pyroptosis-related transcription factor (TF)-microRNA (miRNA)-gene regulatory networks in mediating Ang II-associated cardiac remodeling remains largely unknown. Therefore, we identified the pyroptosis-related hub genes and constructed a transcription factor (TF)-miRNA-target gene regulatory network using bioinformatic tools to elucidate the pathogenesis of Ang II-induced cardiac remodeling. METHODS: The pyroptosis-related differentially expressed genes (DEGs) were identified from the cardiac remodeling-related dataset GSE47420. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) analysis were performed to identify the pyroptosis-related hub DEGs. A TF-miRNA-target gene network was constructed and further validated by quantitative real-time polymerase chain reaction (qRT-PCR) in animal experiments. The correlation between the pyroptosis-related hub DEGs and cardiac remodeling was evaluated using comparative toxicogenomics database. The drug-gene interaction analysis was performed to identify potential drugs that target the pyroptosis-related hub DEGs. RESULTS: A total of 32 pyroptosis-related DEGs were identified and enriched in the inflammation-related pathways by KEGG analysis. 13 of the 32 pyroptosis-related DEGs were identified as hub DEGs. Furthermore, a TF-miRNA-target gene regulatory network containing 16 TFs, 6 miRNAs, and 5 hub target genes was constructed. The five pyroptosis-related hub target genes (DDX3X, ELAVL1, YWHAZ, STAT3, and EED) were identified as crucial cardiac remodeling-related genes using the comparative toxicogenomics database (CTD) database. Five drugs including celecoxib were identified as potential drugs for the treatment of cardiac remodeling. Finally, the expression levels of two top-ranked TF-miRNA-target genes axis were verified by qRT-PCR in mice with Ang II-induced cardiac remodeling and found to be generally consistent with the microarray results. CONCLUSIONS: This study constructed a pyroptosis-related TF-miRNA-target gene regulatory network for Ang II-induced cardiac remodeling. Five pyroptosis-related genes (DDX3X, ELAVL1, YWHAZ, STAT3, and EED) can be considered the core genes associated with pyrotposis-related cardiac remodeling. The findings of this study provide new insights into the molecular mechanisms of Ang II-induced cardiac remodeling and may serve as potential biomarkers or therapeutic targets for Ang II-induced cardiac remodeling.

Novel Nanoprobe with Combined Ultrasonography/Chemical Exchange Saturation Transfer Magnetic Resonance Imaging for Precise Diagnosis of Tumors.

Given that cancer mortality is usually due to a late diagnosis, early detection is crucial to improve the patient's results and prevent cancer-related death. Imaging technology based on novel nanomaterials has attracted much attention for early-stage cancer diagnosis. In this study, a new block copolymer, poly(ethylene glycol)-poly(l-lactide) diblock copolymer (PEG-PLLA), was synthesized by the ring-opening polymerization method and thoroughly characterized using Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance spectroscopy (H-NMR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The obtained PEG-PLLA was used to prepare nanoparticles encapsulated with perfluoropentane and salicylic acid by the emulsion-solvent evaporation method, resulting in a new dual-mode nano-image probe (PEG-PLLA@SA·PFP). The zeta potential and mean diameter of the obtained nanoparticles were measured using dynamic light scattering (DLS) with a Malvern Zetersizer Nano. The in vitro biocompatibility of the PEG-PLLA nanoparticles was evaluated with cell migration, hemolysis, and cytotoxicity assays. Ultrasonic imaging was performed using an ultrasonic imaging apparatus, and chemical exchange saturation transfer (CEST) MRI was conducted on a 7.0 T animal scanner. The results of IR and NMR confirmed that the PEG-PLLA was successfully synthesized. The particle size and negative charge of the nanoparticles were 223.8 ± 2.5 nm and -39.6 ± 1.9 mV, respectively. The polydispersity of the diameter was 0.153 ± 0.020. These nanoparticles possessed good stability at 4 °C for about one month. The results of cytotoxicity, cell migration, and hemolysis assays showed that the carrier material was biocompatible. Finally, PEG-PLLA nanoparticles were able to significantly enhance the imaging effect of tumors by the irradiation of ultrasound and saturation by a radiofrequency pulse, respectively. In conclusion, these nanoparticles exhibit promising dual-mode capabilities for US/CEST MR imaging.

A case report on clinical features, diagnosis, and treatment of rhino-orbito-cerebral mucormycosis.

BACKGROUND: Rhino-orbito-cerebral mucormycosis (ROCM) is an opportunistic pathogenic fungal disease caused by the fungus mucor, and it is a life-threatening fungal infection. The ulceration on the skin of the head and neck, accompanied by rhinitis, headache, orbital inflammation, and eyelid edema, should raise a high suspicion of Mucor infection in diabetic patients with inadequately controlled blood glucose. CASE DESCRIPTION: The clinical data of a patient with ROCM were analyzed retrospectively, and the clinical features were analyzed. The patient was admitted to the hospital with "diabetic hyperosmotic coma" after presenting with fatigue, poor appetite, and disturbances in consciousness as initial symptoms. After improving relevant examinations, controlling underlying diseases, and administering antifungal treatment, the final clinical outcome was death. CONCLUSION: ROCM is more prevalent in patients with uncontrolled diabetes and varied clinical manifestations. The characteristic feature is an eschar-like necrosis of the local skin or mucosa. The gold criteria for diagnosis are pathology and fungal culture; imaging examination does not reveal any specific manifestations. Early diagnosis and effective treatment are the keys.

Role of lysosomes in HSV-induced pathogenesis.

HSV can evade host defenses and cause lifelong infection and severe illness. Lysosomes are catabolic organelles that play an important role in the regulation of cellular homeostasis. Lysosomal dysfunction and alterations in the process of autophagy have been identified in a variety of diseases, including HSV infection, and targeting lysosomes is a potential anti-HSV therapeutic strategy. This article reviews the role of lysosomes and lysosome-associated proteins in HSV infection, providing attractive targets and novel strategies for the treatment of HSV infection.

Cu Facet-Dependent Elementary Surface Reaction Kinetics of CO2 Hydrogenation to Methanol Catalyzed by ZrO2/Cu Inverse Catalysts.

ZrO2-Cu-based catalysts are active in catalyzing the hydrogenation of CO2 to methanol. Herein, we report Cu facet effects on the catalytic performance of ZrO2/Cu inverse catalysts in CO2 hydrogenation to methanol using various Cu nanocrystals with well-defined Cu morphologies and facets. The ZrO2-Cu interface is the active site, in which the ZrO2-Cu{100} and ZrO2-Cu{110} interfaces exhibit similar apparent activation energies of ∼42.6 kJ/mol, smaller than that of the ZrO2-Cu{111} interface (∼64.5 kJ/mol). Temporal in situ diffuse reflectance infrared Fourier transform spectroscopy characterization results identify the bridge formate hydrogenation as the rate-determining elementary surface reaction under typical reaction temperatures, whose activation energy is similar at the ZrO2-Cu{100} (∼36.3 kJ/mol) and ZrO2-Cu{110} (∼40.5 kJ/mol) interfaces and larger at the ZrO2-Cu{111} interface (∼54.5 kJ/mol). This fundamental understanding suggests Cu facet engineering as a promising strategy to improve the catalytic performance of ZrO2/Cu inverse catalysts for CO2 hydrogenation to methanol.

LY294002 alleviates bone cancer pain by reducing mitochondrial dysfunction and the inflammatory response.

Bone cancer pain (BCP) is mainly caused by bone metastasis and markedly impairs the functional capacity and daily functions of patients. Neuroinflammation plays a pivotal role in the pathogenesis and maintenance of chronic pain. Oxidative stress in the mitochondria is a key contributor to neuroinflammation and neuropathic pain. Herein, a rat model of BCP was established which was characterized by bone destruction, pain hypersensitivity and motor disability. In the spinal cord, phosphatidylinositol 3­kinase (PI3K)/protein kinase B (Akt) signaling was activated, and the inflammatory response and mitochondrial dysfunction were also observed. The intrathecal injection of LY294002, a selective inhibitor of PI3K/Akt signaling, decreased mechanical pain sensitivity, suppressed spontaneous pain and recovered the motor coordination of rats with BCP. Second, LY294002 treatment blocked spinal inflammation by reducing astrocytic activation and downregulating the expression levels of inflammatory factors, such as NF­κB, IL­1ß and TNF­α. Moreover, LY294002 treatment recovered mitochondrial function by activating the manganese superoxide dismutase enzyme, increasing NADH:ubiquinone oxidoreductase subunit B11 expression, and decreasing BAX and dihydroorotate dehydrogenase expression. LY294002 treatment also increased the mitochondrial membrane potential and decreased the mitochondrial reactive oxygen species levels in C6 cells. On the whole, the results of the present study suggest that the inhibition of PI3K/Akt signaling by LY294002 restores mitochondrial function, suppresses spinal inflammation and alleviates BCP.

GSK-3ß inhibition alleviates arthritis pain via reducing spinal mitochondrial reactive oxygen species level and inflammation.

Pain is the main symptom of osteoarthritis, which severely reduces the patients' quality of life. Stimulated neuroinflammation and elevated mitochondrial oxidative stress are associated arthritis pain. In the present study, arthritis model was established by intra-articular injection of complete Freund's adjuvant (CFA) on mice. Knee swelling, pain hypersensitivity and motor disability were observed in CFA-induced mice. In spinal cord, neuroinflammation was triggered and presented as severe infiltration of inflammatory cells and up-regulated expressions of glial fibrillary acidic protein (GFAP), nuclear factor-kappaB (NF-κB), PYD domains-containing protein 3 (NLRP3), cysteinyl aspartate specific proteinase (caspase-1) and interleukin-1 beta (IL-1ß). Mitochondrial function was disrupted and characterized as elevated expressions of B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax), dihydroorotate dehydrogenase (DHODH) and cytochrome C (Cyto C), and reduced expressions of Bcl-2 and Mn-superoxide dismutase (Mn-SOD) activity. Meanwhile, as a potential target for pain management, glycogen synthase kinase-3 beta (GSK-3ß) activity was up-regulated in CFA induced mice. To explore potential therapeutic options for arthritis pain, GSK-3ß inhibitor TDZD-8 was intraperitoneally injected for three days on CFA mice. Animal behavioral tests found that TDZD-8 treatment elevated mechanical pain sensitivity, suppressed spontaneous pain and recovered motor coordination. Morphological and protein expression analysis indicated that TDZD-8 treatment decreased spinal inflammation score and inflammatory related protein levels, recovered mitochondrial related protein levels, and increased Mn-SOD activity. In summary, TDZD-8 treatment inhibits GSK-3ß activity, reduces mitochondrial mediated oxidative stress, suppresses spinal inflammasome response, and alleviates arthritis pain.

Preparation and antitumor activity of triphenylphosphine-based mitochondrial targeting polylactic acid nanoparticles loaded with 7-hydroxyl coumarin.

Due to the low bioavailability and severe toxic side effects caused by the lack of selectivity of traditional chemotherapy drugs, the targeted delivery of chemotherapy drugs has become the key to tumor treatment. The activity and transmembrane potential of mitochondria in cancer cells were significantly higher than that of normal cells, making them a potential target for chemotherapeutic drug delivery. In this study, triphenylphosphine (TPP) based mitochondria targeting polylactic acid (PLLA) nanoparticles (TPP-PLLA NPs) were synthesized to improve the delivery efficiency of anticancer drugs. The carrier material was characterized by 1H NMR and FT-IR and 7-hydroxyl coumarin (7-HC) was successfully loaded into TPP-PLLA to form 7-HC/TPP-PLLA NPs. Further studies showed that TPP-PLLA NPs were primarily accumulated in the mitochondrial and 7-HC/TPP-PLLA NPs had higher antitumor activity. Taken together, our results indicated that TPP-PLLA NPs could be a promising mitochondria-targeted drug delivery system for cancer therapy.

Citric acid coated ultrasmall superparamagnetic iron oxide nanoparticles conjugated with lactoferrin for targeted negative MR imaging of glioma.

The proposed study was to develop the preparation of ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) modified with citric acid, with surface conjugated with lactoferrin (Lf), which used as a potential targeted contrast agent for magnetic resonance imaging (MRI) of brain glioma. USPIONs were prepared by the thermal decomposition method. The hydrophobic USPIONs were coated with citric acid by the ligand exchange method. Then, Lf was conjugated into the surface of USPIONs. The obtained Lf-USPIONs were analyzed by fourier transform infrared (FTIR) spectroscopy and polyacrylamide gel electrophoresis. The size, size distribution, shape and superparamagnetic property of Lf-USPIONs were investigated with TEM and vibrating sample magnetometer (VSM). Both FTIR and electrophoresis analysis demonstrated the successful conjugation of Lf to the surface of USPIONs. The average size of Lf-USPIONs was about 8.4 ± 0.5 nm, which was determined using the statistics of measured over 100 nanoparticles in the TEM image, with a negative charge of -7.3 ± 0.2 mV. TEM imaging revealed that Lf-USPIONs were good in dispersion and polygonal in morphology. VSM results indicated that Lf-USPIONs were superparamagnetic and the saturated magnetic intensity was about 69.8 emu/g. The Lf-USPIONs also showed good biocompatibility in hemolysis, cytotoxicity, cell migration and blood biochemistry studies. MR imaging results in vitro and in vivo indicated that Lf-USPIONs exhibited good negative contrast enhancement. Taken together, Lf-USPIONs hold great potential for brain gliomas MR imaging as a nanosized targeted contrast agent.

The decade long achievements of China's marine ecological civilization construction (2006-2016).

China needs to balance between current population pressures and a vulnerable marine environment, creating a national, political outline or management strategy dubbed an ecological civilization construction. The nation's effort to protect and maintain a sustainable ocean and address the relevant economic, resource and environmental issues relies on Marine Ecological Civilization (MEC) construction. The quantification of MEC progress is essential to track the management performance and guide the subsequent development and implementation. This study evaluates the performance of China's MEC from 2006 to 2016 based on a comprehensive index system. Our findings are as follows: During 2006-2016, the overall MEC performance score increased from 0.3426 to 0.4850 nationwide. Large space-time variations exist among the eleven coastal regions. The Shandong and Guangdong regions showed relatively good performances, whereas the Jiangsu, Guangxi and Shanghai regions had low scores. A decade long change in MEC scores showed that Hebei achieved the largest increase ratio. Marine management was improved by implementing various conservation strategies by China's government. Marine education and human talent introduction deserve more attention in less developed areas such as Hainan and Guangxi, and poor marine environmental quality was an urgent issue of the Yangtze river estuary economic zone. More accessible marine monitoring dataset are needed to track future space-time progress dynamics towards MEC construction. Our results provide a decade long retrospect of China's MEC achievements, and the quantified evaluation for each coastal region can provide valuable insight to policy-makers.

Resveratrol suppresses bone cancer pain in rats by attenuating inflammatory responses through the AMPK/Drp1 signaling.

Bone cancer pain (BCP) is induced by primary bone cancer and secondary bone metastasis. During BCP pathogenesis, activated spinal astrocytes release proinflammatory cytokines, which participate in pain information transmission. In this study, we found that BCP rats showed disruption of trabecular bone structure, mechanical allodynia, and spinal inflammation. Moreover, reduced adenosine monophosphate-activated protein kinase (AMPK) activity, increased mitochondrial fission-associated protein Drp1 GTPase activity accompanied by the dysfunction of mitochondrial function, and abnormal BAX and Bcl-2 expression were found in the spinal cord of BCP rats. Notably, these alterations are reversed by resveratrol (Res) administration. Cell experiment results demonstrated that Res promotes mitochondrial function by activating AMPK, decreasing Drp1 activity, and inhibiting tumor necrosis factor-α-induced mitochondrial membrane potential reduction. Taken together, these results indicate that Res suppresses BCP in rats by attenuation of the inflammatory responses through the AMPK/Drp1 signaling pathway.

Klotho inhibits angiotensin II-induced cardiac hypertrophy, fibrosis, and dysfunction in mice through suppression of transforming growth factor-ß1 signaling pathway.

Recent studies have revealed critical roles of transforming growth factor-ß1 (TGF-ß1) and microRNA-132 (miR-132), a downstream mediator of TGF-ß1, in the pathogenesis of cardiac remodeling. In this study, we tested whether the antiaging protein klotho modifies angiotensin II (Ang II)-induced cardiac remodeling through regulating TGF-ß1-miR-132 axis. We found that both klotho and the TGF-ß1 inhibitor LY364947 significantly inhibited cardiac hypertrophy, fibrosis, and dysfunction in Ang II-infused mice, as evidenced by the ratios of heart weight to body weight (HW/BW), heart weight to tibial length (HW/TL), cardiomyocyte cross-sectional area, fibrotic area, and expression of prohypertrophic genes (ANP, ß-MHC) and fibrotic marker genes (α-SMA, collagen I), echocardiographic parameters. Meanwhile, klotho also significantly inhibited Ang II-induced protein expression of TGF-ß1 and phosphorylated Smad2/3 in the heart tissues and cultured cardiomyocytes and cardiac fibroblasts. In vitro experiments demonstrated that Ang II-induced cardiomyocyte hypertrophy and proliferation and activation of cardiac fibroblasts were markedly inhibited by klotho, LY364947 or the miR-132 inhibitor anti-miR-132. Both klotho and the TGF-ß1 inhibitor LY364947 downregulated the miR-132 expression. Additionally, klotho decreased Ang II-induced protein expressions of cardiac fibroblast growth factor (FGF)23 in vivo and in vitro. The decreased protein levels of klotho in serum and renal tissues of Ang II-infused mice were elevated by klotho. Klotho downregulated the protein levels of TGF-ß1 in renal tissues of Ang II-infused mice. In conclusion, our results suggest that klotho prevents Ang II-induced cardiac remodeling and dysfunction through modifying the TGF-ß1-miR-132 axis, providing an experimental basis for clinical treatment on cardiac remodeling.