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ABSTRACTUrban Green Spaces (UGSs) can provide social and ecological benefits, and the coordination of these two functions will largely advance human-nature harmony in cities. As such, we proposed a comprehensive framework to evaluate UGSs multifunctionality, i.e. the coupling coordination relationship of ecological connectivity and spatial accessibility of UGSs. Wuhan City in Central China was taken as a case study, and multiple ecosystem service values of green space patches and the disordered use of UGSs multifunctionality were explored. The results demonstrated low-level coupling coordination of UGSs multifunctionality in Wuhan. More than 70% of UGSs were imbalanced, 27.91% of which featured small sizes, low connectivity and accessibility. We suggest that planners should optimize UGSs arrangement to improve species reachability, especially for species with dispersal distance less than 4 km, and to create 15-minute community life circles for residents at the same time. Our findings are expected to support the promotion of UGSs multifunctionality and the balance of urban development and habitat conservation.

Quantitative measurement of urban green spaces (UGSs) plays a fundamental role in enhancing their ecological functions and services. Current studies have not adequately analyzed the multifunctional characteristics and the diverse benefits of urban green spaces at the national scale. This study developed a multidimensional indicator system in terms of scale, pattern, and services to measure green spaces in 285 prefecture-level cities in China. The influences of different geographic zones and urban development on UGS characteristics were also investigated. The results showed that per capita area of urban green spaces were significantly different between the two sides of the “Botai Line”, and the UGS structure was mainly dominated by woodlands. Urban green spaces in the central and east had higher fragmentation, lower landscape diversity, and weaker connectivity. The spatial accessibility of green spaces exhibited a “low–high–medium” pattern from north to south in China, with central-eastern China experiencing the worst equity in green space supply. Overall, cities with higher integrated benefits of green spaces were mainly located in Northeast and North China. Type I large cities had higher ratings for UGS characteristics compared with the other types of cities. These findings can serve as solid guidance for cities seeking to build green space systems with highly integrated socio–ecological benefits.

Abstract Background Previous studies have shown a close association between an altered immune system and Parkinson's disease (PD). Neuroinflammation inhibition may be an effective measure to prevent PD. Recently, numerous reports have highlighted the potential of hydroxy-carboxylic acid receptor 2 (HCA2) in inflammation-related diseases. Notably, the role of HCA2 in neurodegenerative diseases is also becoming more widely known. However, its role and exact mechanism in PD remain to be investigated. Nicotinic acid (NA) is one of the crucial ligands of HCA2, activating it. Based on such findings, this study aimed to examine the effect of HCA2 on neuroinflammation and the role of NA-activated HCA2 in PD and its underlying mechanisms. Methods For in vivo studies, 10-week-old male C57BL/6 and HCA2−/− mice were injected with LPS in the substantia nigra (SN) to construct a PD model. The motor behavior of mice was detected using open field, pole-climbing and rotor experiment. The damage to the mice's dopaminergic neurons was detected using immunohistochemical staining and western blotting methods. In vitro, inflammatory mediators (IL-6, TNF-α, iNOS and COX-2) and anti-inflammatory factors (Arg-1, Ym-1, CD206 and IL-10) were detected using RT-PCR, ELISA and immunofluorescence. Inflammatory pathways (AKT, PPARγ and NF-κB) were delineated by RT-PCR and western blotting. Neuronal damage was detected using CCK8, LDH, and flow cytometry assays. Results HCA2−/− increases mice susceptibility to dopaminergic neuronal injury, motor deficits, and inflammatory responses. Mechanistically, HCA2 activation in microglia promotes anti-inflammatory microglia and inhibits pro-inflammatory microglia by activating AKT/PPARγ and inhibiting NF-κB signaling pathways. Further, HCA2 activation in microglia attenuates microglial activation-mediated neuronal injury. Moreover, nicotinic acid (NA), a specific agonist of HCA2, alleviated dopaminergic neuronal injury and motor deficits in PD mice by activating HCA2 in microglia in vivo. Conclusions Niacin receptor HCA2 modulates microglial phenotype to inhibit neurodegeneration in LPS-induced in vivo and in vitro models.

Sustainable land use should balance the competing needs for development and protection. Land-use intensification facilitates material benefits from ecosystem, while potentially undermining the capacity of regulate the life-support environment and thus altering trade-offs between ecosystem services (ES). However, there remains a limited understanding of how land-use intensity (LUI) affects the spatial heterogeneity of ES relationships. To address this issue, we first propose an ES synergies (ESS) index, to clarify site-specific ES relationships, based on a combination of the production possibility frontier (PPF) and the technique for order preference by similarity to the ideal solution (TOPSIS). Then, we assess the nonlinear impacts of LUI on ESS, using the generalized additive models (GAMs). A case study was conducted in the Three Gorges region of central China, due to the dilemma between intensive development for poverty alleviation and water-soil retention for ecological protection. The results showed that an increase in LUI caused different rates of decline in ESS. Land-use intensification increased resource inputs and anthropogenic disturbances within entire land parcels, thus disrupting the synergistic relationships between several ES. Specifically, the synergies between water retention and carbon sequestration or biodiversity conservation decreased by more than three times as much as those between water retention and food production. Excessive LUI will reduce the provision of carbon sequestration and biodiversity conservation compared to that of food production for the same level of water retention. However, moderate LUI can promote the synergistic provision of multiple services. For example, an LUI threshold of 2.5, which maximized the synergies of water-soil retention with other ES, showed the optimal balance of diverse ecological benefits at the highest level of intensity. Our study is expected to extend existing knowledge on the spatial heterogeneity of ES relationships by considering site-specific land use, and to mitigate the costs of land management due to ES trade-offs.

More than 10% of the world’s population already suffers from varying degrees of diabetes mellitus (DM), but there is still no cure for the disease. Cardiovascular disease (CVD) is one of the most common and dangerous of the many health complications that can be brought on by DM, and has become the leading cause of death in people with diabetes. While research on DM and associated CVD is advancing, the specific mechanisms of their development are still unclear. Given the threat of DM and CVD to humans, the search for new predictive markers and therapeutic ideas is imminent. Non-coding RNAs (ncRNAs) have been a popular subject of research in recent years. Although they do not encode proteins, they play an important role in living organisms, and they can cause disease when their expression is abnormal. Numerous studies have observed aberrant ncRNAs in patients with DM complications, suggesting that they may play an important role in the development of DM and CVD and could potentially act as biomarkers for diagnosis. There is additional evidence that treatment with existing drugs for DM, such as metformin, alters ncRNA expression levels, suggesting that regulation of ncRNA expression may be a key mechanism in future DM treatment. In this review, we assess the role of ncRNAs in the development of DM and CVD, as well as the evidence for ncRNAs as potential therapeutic targets, and make use of bioinformatics to analyze differential ncRNAs with potential functions in DM.

Hepatocellular carcinoma (HCC) is a highly mortal type of primary liver cancer. Abnormal epigenetic modifications are present in HCC, and RNA modification is dynamic and reversible and is a key post-transcriptional regulator. With the in-depth study of post-transcriptional modifications, RNA modifications are aberrantly expressed in human cancers. Moreover, the regulators of RNA modifications can be used as potential targets for cancer therapy. In RNA modifications, N6-methyladenosine (m6A), N7-methylguanosine (m7G), and 5-methylcytosine (m5C) and their regulators have important regulatory roles in HCC progression and represent potential novel biomarkers for the confirmation of diagnosis and treatment of HCC. This review focuses on RNA modifications in HCC and the roles and mechanisms of m6A, m7G, m5C, N1-methyladenosine (m1A), N3-methylcytosine (m3C), and pseudouridine (ψ) on its development and maintenance. The potential therapeutic strategies of RNA modifications are elaborated for HCC.

Due to powerful drug resistance and fatal toxicity of methicillin-resistant Staphylococcus aureus (MRSA), therapeutic strategies against virulence factors present obvious advantages since no evolutionary pressure will induce bacterial resistance. Alpha-hemolysin (Hla) is an extracellular toxin secreted by Staphylococcus aureus and contributes to bacterial pathogenicity. Herein, we identified a natural product 2,3-dehydrokievitone (2,3-DHKV) for inhibiting Hla activity of MRSA strain USA300 but not affecting bacteria growth. 2,3-DHKV significantly decreased hemolysin expression in a dose-dependent manner, but it did not potently neutralize hemolysin activity. Subsequently, cellular thermal shift and heptamer formation assays confirmed that 2,3-DHK affects hemolytic activity through indirect binding to Hla. RT-qPCR and western blot revealed that 2,3-DHKV suppressed Hla expression at the mRNA and protein levels, and further decreased accessory gene regulator A (agrA) transcription levels. We also observed that 2,3-DHK significantly attenuated the damage of A549 cells by S. aureus and reduced the release of lactate dehydrogenase (LDH). Moreover, in the MRSA-induced pneumonia mouse model, 2,3-DHK treatment prolonged the life span of mice and reduced the bacterial load in the lungs, which significantly alleviated the damage to the lungs. In summary, this study proved that 2,3-DHK as a Hla inhibitor is a potential antivirulence agent against MRSA infection.

Abstract Background Galangin has been extensively studied as the antitumor agent in various cancers. However, the effect of galangin in hepatocellular carcinoma (HCC) remains elusive. Methods Using RNA sequencing, the differential expression of lncRNA in human HCC cell line with highly metastatic potential (MHCC97H) cells treated with galangin was investigated. Furthermore, H19 expression pattern was also determined in MHCC97H cells following treatment with galangin. In addition, knockdown and overexpression of H19 was performed to analyze the effect of the expression pattern of H19 on cell apoptosis, cell cycle, migration, and invasion in HCC cells. Moreover, the in vivo effect of galangin on tumor development was also determined in nude mice. In order to analyze loss expression of H19 in vivo, clustered regularly interspaced short palindromic repeats/Cas9 (CRISPR/Cas9) was used. Results Total of 50 lncRNAs were significantly differentially expressed in MHCC97H cells treated with galangin. Besides, the expression of H19 was markedly reduced following treatment with galangin in MHCC97H cells. Compared to the Control group, the galangin‐treated group inhibited cell migration and invasion. Knockdown of H19 expression showed increased cell apoptosis and decreased invasion. In addition, RNA‐seq data also identified 161 mRNA which was significantly differentially expressed following treatment with galangin. To further determine the underlying mechanism, p53 protein was analyzed. Notably, the results indicated that knockdown of H19 and miR675 induced the expression of p53, eventually promoting cell apoptosis in MHCC97H cells. These results indicated that galangin promoted cell apoptosis through reduced the expression of H19 and miR675 in MHCC97H cells. The in vivo result showed that compared to the Con, tumor growth was remarkably suppressed with loss expression of H19. Conclusion Our data suggested that galangin has a crucial role in hepatocarcinogenesis through regulating the expression pattern of H19.

In recent years, the morbidity and mortality of gastrointestinal cancer have remained high in China. Due to the deep location of the gastrointestinal organs, such as gastric cancer, the early symptoms of cancer are not obvious. It is generally discovered at an advanced stage with distant metastasis and lymph node infiltration, making it difficult to cure. Therefore, there is a significant need for novel technologies that can effectively diagnose and treat gastrointestinal cancer, ultimately reducing its mortality. Gold nanoparticles (GNPs), a type of nanocarrier with unique optical properties and remarkable biocompatibility, have the potential to influence the fate of cancer by delivering drugs, nucleic acids to cancer cells and tissues. As a safe and reliable visualization agent, GNPs can track drugs and accurately indicate the location and boundaries of cancer, opening up new possibilities for cancer treatment. In addition, GNPs have been used in photodynamic therapy to deliver photosensitizers, as well as in combination with photothermal therapy. Therefore, GNPs can be used as a safe and effective nanomaterial in the treatment and diagnosis of gastrointestinal cancer.

Gastric cancer and colorectal cancer are malignant tumors found in the human gastrointestinal tract. Bidirectional communication between tumor cells and their microenvironment can be realized through the transmission of exosomes—small, cell-derived vesicles containing complex RNA and proteins. Exosomes play an important role in the proliferation, metastasis, immune response, and drug resistance of cancer cells. In this review, we focus on the role and application of exosomes in gastric and colorectal cancer. We also summarize the role of exosomes secreted by different types of cells in tumor development and as drug carriers in cancer treatment.

Parkinson’s disease (PD), the second primary neurodegenerative disease affecting human health, is mainly characterized by dopaminergic neuron damage in the midbrain and the clinical manifestation of movement disorders. Studies have shown that neuroinflammation plays an important role in the progression of PD. Excessively activated microglia produce several pro-inflammatory mediators, leading to damage to the surrounding neurons and finally inducing neurodegeneration. Echinocystic acid (EA) exhibits an anti-inflammatory effect in peripheral tissues. However, whether it inhibited neuroinflammation remains unclear. Therefore, the current study investigates the effect of EA on neuroinflammation and whether it can improve PD symptoms through inhibiting neuroinflammation. In our experiments, we discovered that EA inhibited the production of pro-inflammatory mediators in LPS-exposed BV2 cells. Further mechanism-related studies revealed that EA inhibited inflammation by activating PI3K/Akt and inhibiting NF-κB and MAPK signal pathways in LPS-induced BV2 cells. Research revealed that EA eases microglia-mediated neuron death in SN4741 and SHSY5Y cells. In in vivo studies, the results demonstrated that EA improves weight loss and behavioral impairment in MPTP-induced mice. Further studies have revealed that EA inhibited dopaminergic neuron damage and inflammation in the mice midbrain. In conclusion, our study demonstrated that EA inhibits neuroinflammation and exerts neuroprotective effects by activating PI3K/Akt and inhibiting NF-κB and MAPK signal pathways in vivo and in vitro.

Extracellular vesicles (EVs) exert their biological functions by delivering proteins, metabolites, and nucleic acids to recipient cells. EVs play important roles in cancer development. The anti-tumor effect of EVs is by their cargos carrying proteins, metabolites, and nucleic acids to affect cell-to-cell communication. The characteristics of cell-to-cell communication can potentially be applied for the therapy of cancers, such as gastric cancer. In addition, EVs can be used as an effective cargos to deliver ncRNAs, peptides, and drugs, to target tumor tissues. In addition, EVs have the ability to regulate cell apoptosis, autophagy, proliferation, and migration of cancer cells. The ncRNA and peptides that were engaged with EVs were associated with cell signaling pathways in cancer development. This review focuses on the composition, cargo, function, mechanism, and application of EVs in cancers.

Habitat fragmentation has largely reduced biodiversity in the urban fringe. The prioritization of individual habitat patches can provide spatially explicit guidance for ecological conservation and restoration. Numerous studies discussed the effectiveness of purely spatial connectivity metrics to rank the conservation priority of habitats, but hardly resolved this issue in a dynamic landscape context. Meanwhile, spatio-temporal connectivity metrics were usually applied at the landscape scale, but are rarely extended to determine habitat priority at the patch scale. As such, we extend a generalized betweenness centrality metric into spatio-temporal connectivity networks to evaluate conservation priorities of individual habitat patches from a dynamic landscape perspective. The contribution rates of spatio-temporal connectivity metrics are examined at varying dispersal distances of the target species. Caidian District, the fringe of Wuhan City in central China, is taken as a case study. The results illustrate that a net decrease in habitat amounts and quality from 2005 to 2015 was mainly caused by urban expansion and agricultural production. The positive contribution rates of spatio-temporal connectivity metrics are observed at distance thresholds exceeding 200 m at the landscape scale, which allows us to capture the response of habitat priority to landscape dynamics. Accordingly, we develop a balanced conservation strategy for multiple species and the targeted conservation measures based on the coupled analysis of quality and conservation priority of habitat patches. Our findings are expected to provide solid support for biodiversity conservation in urban growth.

Microglia, the main immune cells in the brain, participate in the innate immune response in the central nervous system (CNS). Studies have shown that microglia can be polarized into pro-inflammatory M1 and anti-inflammatory M2 phenotypes. Accumulated evidence suggests that over-activated M1 microglia release pro-inflammatory mediators that damage neurons and lead to Parkinson’s disease (PD). In contrast, M2 microglia release neuroprotective factors and exert the effects of neuroprotection. Camptothecin (CPT), an extract of the plant Camptotheca acuminate, has been reported to have anti-inflammation and antitumor effects. However, the effect of CPT on microglia polarization and microglia-mediated inflammation responses has not been reported. In our study we found that CPT improved motor performance of mice and reduced the loss of neurons in the substantia nigra (SN) of the midbrain in LPS-injected mice. In the mechanism study, we found that CPT inhibited M1 polarization of microglia and promotes M2 polarization via the AKT/Nrf2/HO-1 and NF-κB signals. Furthermore, CPT protected the neuroblastoma cell line SH-SY5Y and dopaminergic neuron cell line MN9D from damage mediated by microglia activation. In conclusion, our results demonstrate that CPT regulates the microglia polarization phenotype via activating AKT/Nrf2/HO-1 and inhibiting NF-κB pathways, inhibits neuro-inflammatory responses, and exerts neuroprotective effects in vivo and in vitro.

Parkinson’s disease (PD) is a neurodegenerative disease in which neuronal apoptosis and associated inflammation are involved in its pathogenesis. However, there is still no specific treatment that can stop PD progression. Isoalantolactone (IAL) plays a role in many inflammation-related diseases. However, its effect and mechanism in PD remain unclear. In this study, results showed that IAL administration ameliorated 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD-related pathological impairment and decreased motor activity in mice. Results from in vitro mechanistic studies showed that IAL regulated apoptosis-related proteins by activating the AKT/Nrf2 pathway, thereby suppressing the apoptosis of SN4741 cells induced by N-methyl-4-phenylpyridinium Iodide (MPP+). On the other hand, IAL inhibited LPS-induced release of pro-inflammatory mediators in BV2 cells by activating the AKT/Nrf2/HO-1 pathway and inhibiting the NF-κB pathway. In addition, IAL protected SN4741 from microglial activation-mediated neurotoxicity. Taken together, these results highlight the beneficial role of IAL as a novel therapy and potential PD drug due to its pharmacological profile.

α-Cyperone, extracted from Cyperus rotundus, has been reported to inhibit microglia-mediated neuroinflammation. Oxidative stress and apoptosis play crucial roles in the course of Parkinson’s disease (PD). PD is a common neurodegenerative disease characterized by selective death of dopaminergic neurons. This study was designed to investigate the neuroprotective effects of α-cyperone against hydrogen peroxide (H2O2)-induced oxidative stress and apoptosis in dopaminergic neuronal SH-SY5Y cells. Neurotoxicity was assessed by MTT assay and the measurement of lactic dehydrogenase (LDH) release. The level of reactive oxygen species (ROS) was measured by dichlorodihydrofluorescin diacetate (DCFH-DA) staining. The apoptosis of SH-SY5Y cells was evaluated by annexin-V-FITC staining. The translocation of NF-E2-related factor 2 (Nrf2) was determined by western blot and immunofluorescence staining. Western blot analysis was conducted to determine the expression level of cleaved-caspase-3, the pro-apoptotic factor Bax, and the anti-apoptotic factor, Bcl-2. The results showed that α-cyperone substantially decreased H2O2-induced death, release of LDH, and the production of ROS in SH-SY5Y cells. In addition, we found that α-cyperone attenuated H2O2-induced cellular apoptosis. Moreover, α-cyperone remarkably reduced the expression of cleaved-caspase-3 and Bax, and upregulated Bcl-2. Furthermore, α-cyperone enhanced the nuclear translocation of Nrf2. Pretreatment with brusatol (BT, an Nrf2 inhibitor) attenuated α-cyperone-mediated suppression of ROS, cleaved-caspase-3, and Bax, as well as α-cyperone-induced Bcl-2 upregulation in H2O2-treated SH-SY5Y cells. α-cyperone neuroprotection required Nrf2 activation. In conclusion, α-cyperone attenuated H2O2-induced oxidative stress and apoptosis in SH-SY5Y cells via the activation of Nrf2, suggesting the potential of this compound in the prevention and treatment of PD.

Abstract Objective This study aimed to reveal the mitochondrial genomes (mtgenomes) of Tetrix japonica and Alulatettix yunnanensis, and the phylogenetics of Orthoptera species. Methods The mtgenomes of A. yunnanensis and T. japonica were firstly sequenced and assembled through partial sequences amplification, and then the genome organization and gene arrangement were analyzed. Based on nucleotide/amino acid sequences of 13 protein-coding genes and whole mtgenomes, phylogenetic trees were established on 37 Orthoptera species and 5 outgroups, respectively. Results Except for a regulation region (A+T rich region), a total of 37 genes were found in mtgenomes of T. japonica and A. yunnanensis, including 13 protein-coding genes, 2 ribosomal RNA genes, and 22 transfer RNA genes, which exhibited similar characters with other Orthoptera species. Phylogenetic tree based on 13 concatenated protein-coding nucleotide sequences were considered to be more suitable for phylogenetic reconstruction of Orthoptera species than amino acid sequences and mtgenomes. The phylogenetic relationships of Caelifera species were Acridoidea and Pamphagoidea > Pyrgomorphoidea > Pneumoroidea > Eumastacoidea > Tetrigoidea > Tridactyloidea. Besides, a sister-group relationship between Tettigonioidea and Rhaphidophoroidea was revealed in Ensifera. Conclusion Concatenated protein-coding nucleotide sequences of 13 genes were suitable for reconstruction of phylogenetic relationship in orthopteroid species. Tridactyloidea was a sister group of Tetrigoidea in Caelifera, and Rhaphidophoroidea was a sister group of Tettigonioidea in Ensifera.

The correct urban building layout is an important influencing factor in urban ventilation, and the heat island effect has become an important factor affecting the quality of urban life. Optimization of the urban building layout can play a role in mitigating the heat island effect. The traditional ventilation corridor analysis method, based on a least-cost path analysis, can only generate a few main ventilation corridors. It is difficult to obtain global ventilation results covering the whole study area using this method of analysis. On the basis of urban morphology and a least-cost path analysis, this study proposes a “least cumulative ventilation cost” method for analyzing urban ventilation. Taking Wuhan downtown as a research area, the urban ventilation environment under different wind directions and seasons was analyzed. This method can effectively express the ventilation conditions throughout the whole study area and can simultaneously express the quality of the generated corridors effectively. The results show that Wuhan has three levels of ventilation corridor. Moreover, the ventilation conditions in Wuchang (Wuchang, Qingshan, and Hongshan) are better than those in Hankou (Qiaokou, Jianghan, and Jiang’an).

Microglia are the brain's immune cells and play an important role in regulating the microenvironment in the central nervous system. Activated microglia are capable of acquiring the pro-inflammatory (M1) phenotype and anti-inflammatory (M2) phenotype. Overactivation of microglia is neurotoxic and may lead to neuroinflammatory brain disorders. Neuroinflammation in the brain plays a crucial role part in the pathophysiology of many psychiatric and neurological diseases. The inhibition of M1 microglia and promotion of M2 microglia was demonstrated to treat and prevent these diseases through reduced neuroinflammation. Isovitexin (IVX) has anti-inflammatory properties and passes through the blood-brain barrier; however, the molecular mechanism that modulates IVX-mediated microglial polarization remains unclear. In BV-2 cells and mouse primary microglia, IVX suppressed the expression of M1 microglial markers, enhanced the expression of M2 microglial markers, and enhanced the release of interleukin 10 (IL-10). IVX promoted the expression of peroxisome proliferator-activated receptor-γ (PPARγ) and PPARγ coactivator-1α (PGC-1α) in LPS-induced microglial activation. The inhibition of PPARγ and PGC-1α attenuated the regulatory effect of IVX in LPS-induced microglial polarization. IVX increased the expression of p-CaMKKβ, p-AMPK, and PGC-1α in BV-2 cells. Inhibition of CaMKKβ with STO-609 or knockdown of CaMKKβ with CaMKKβ siRNA attenuated IVX-mediated M2 microglial polarization in LPS-treated cells. In LPS-treated mice, the inhibition of CaMKKβ and PGC-1α attenuated the IVX-mediated prevention of sickness behavior and enhanction of IVX-mediated M2 microglial polarization. IVX promoted M2 microglial polarization which exerted anti-inflammatory effects on LPS-induced neuroinflammation via the activation of the CaMKKβ/AMPK-PGC-1α signaling axis.

Abstract The sexually dimorphic expression of H19/IGF2 is evolutionarily conserved. To investigate whether the expression of H19/IGF2 in the female porcine eye is sex-dependent, gene expression and methylation status were evaluated using quantitative real-time PCR (qPCR) and bisulfite sequencing PCR (BSP). We hypothesized that H19/IGF2 might exhibit a different DNA methylation status in the female eye. In order to evaluate our hypothesis, parthenogenetic (PA) cells were used for analysis by qPCR and BSP. Our results showed that H19 and IGF2 were over-expressed in the female eye compared with the male eye (3-fold and 2-fold, respectively). We observed a normal monoallelic methylation pattern for H19 differentially methylated regions (DMRs). Compared with H19 DMRs, IGF2 DMRs showed a different methylation pattern in the eye. Taken together, these results suggest that elevated expression of H19/IGF2 is caused by a specific chromatin structure that is regulated by the DNA methylation status of IGF2 DMRs in the female eye.

Parkinson's disease (PD) is a common neurodegenerative disease characterized by selective loss of dopaminergic neurons in the substantia nigra (SN). Neuroinflammation induced by over-activation of microglia leads to the death of dopaminergic neurons in the pathogenesis of PD. Therefore, downregulation of microglial activation may aid in the treatment of PD. Polydatin (PLD) has been reported to pass through the blood-brain barrier and protect against motor degeneration in the SN. However, the molecular mechanisms underlying the effects of PLD in the treatment of PD remain unclear. The present study aimed to determine whether PLD protects against dopaminergic neurodegeneration by inhibiting the activation of microglia in a rat model of lipopolysaccharide (LPS)-induced PD. Our findings indicated that PLD treatment protected dopaminergic neurons and ameliorated motor dysfunction by inhibiting microglial activation and the release of pro-inflammatory mediators. Furthermore, PLD treatment significantly increased levels of p-AKT, p-GSK-3βSer9, and Nrf2, and suppressed the activation of NF-κB in the SN of rats with LPS-induced PD. To further explore the neuroprotective mechanism of PLD, we investigated the effect of PLD on activated microglial BV-2 cells. Our findings indicated that PLD inhibited the production of pro-inflammatory mediators and the activation of NF-κB pathways in LPS-induced BV-2 cells. Moreover, our results indicated that PLD enhanced levels of p-AKT, p-GSK-3βSer9, and Nrf2 in BV-2 cells. After BV-2 cells were pretreated with MK2206 (an inhibitor of AKT), NP-12 (an inhibitor of GSK-3β), or Brusatol (BT; an inhibitor of Nrf2), treatment with PLD suppressed the activation of NF-κB signaling pathways and the release of pro-inflammatory mediators in activated BV-2 cells via activation of the AKT/GSK3β-Nrf2 signaling axis. Taken together, our results are the first to demonstrate that PLD prevents dopaminergic neurodegeneration due to microglial activation via regulation of the AKT/GSK3β-Nrf2/NF-κB signaling axis.

Background/Aims: GLP-2 has been shown to exert anti-inflammatory effects, but the underlying molecular mechanisms remained undefined. As macrophages are important in the development and maintenance of inflammation, we investigated whether exogenous GLP-2 modulates the expression of pro-inflammatory proteins in LPS stimulated murine peritoneal macrophages. Methods: Macrophages were pretreated with various concentrations of GLP-2 for 1 h and then stimulated with LPS. The effects on pro-inflammatory enzymes (iNOS and COX-2), and pro-inflammatory cytokines (TNF-a, IL-1ß and IL-6) were analysed by Western blotting, ELISA and qRT-PCR. We also examined whether NF-κB or MAPK signaling was involved in the effects of GLP-2. Results: In macrophages, GLP-2 blunted the effect of LPS on protein and mRNA expression levels of iNOS, COX-2, TNF-a, IL-1ß and IL-6. Pre-incubation of macrophages with GLP-2 also blunted LPS-induced IκB-a degradation, IκB-a phosphorylation and NF-κB translocation. In the presence of GLP-2, the effect of LPS treatment on ERK phosphorylation was also profoundly blunted. GLP-2 did, however, not significantly modify the effects of LPS on p38 and JNK activities. Conclusions: These findings demonstrate that in LPS primed macrophages, GLP-2 reduced pro-inflammatory enzymes and cytokine production via mechanisms involving the suppression of NF-κB activity and ERK phosphorylation.

The soil monitoring network plays an important role in detecting the spatial distribution of soil attributes and facilitates sustainable land-use decision making. Reduced costs, higher speed, greater scope, and a loss of accuracy are necessary to design a regional monitoring network effectively. In this paper, we present a stochastic optimization design method for regional soil carbon and water content monitoring networks with a minimum sample size based on a modified particle swarm optimization algorithm equipped with multiobjective optimization technique. Our effort is to reconcile the conflicts between various objectives, that is, kriging variance, survey budget, spatial accessibility, spatial interval, and the amount of monitoring sites. We applied the method to optimize the soil monitoring networks in a semiarid loess hilly area located in northwest China. The results reveal that the proposed method is both effective and robust and outperforms the standard binary particle swarm optimization and spatial simulated annealing algorithm.

BACKGROUND: Earthworms are an ecosystem's engineers, contributing to a wide range of nutrient cycling and geochemical processes in the ecosystem. Their activities can increase rates of silicate mineral weathering. Their intestinal microbes usually are thought to be one of the key drivers of mineral degradation mediated by earthworms,but the diversities of the intestinal microorganisms which were relevant with mineral weathering are unclear. METHODOLOGY/PRINCIPAL FINDINGS: In this report, we show earthworms' effect on silicate mineral weathering and the responses of bacterial communities in their gut and surrounding substrates after being fed with potassium-bearing rock powder (PBRP). Determination of water-soluble and HNO(3)-extractable elements indicated some elements such as Al, Fe and Ca were significantly released from mineral upon the digestion of earthworms. The microbial communities in earthworms' gut and the surrounding substrates were investigated by amplified ribosomal DNA restriction analysis (ARDRA) and the results showed a higher bacterial diversity in the guts of the earthworms fed with PBRP and the PBRP after being fed to earthworms. UPGMA dendrogram with unweighted UniFrac analysis, considering only taxa that are present, revealed that earthworms' gut and their surrounding substrate shared similar microbiota. UPGMA dendrogram with weighted UniFrac, considering the relative abundance of microbial lineages, showed the two samples from surrounding substrate and the two samples from earthworms' gut had similarity in microbial community, respectively. CONCLUSIONS/SIGNIFICANCE: Our results indicated earthworms can accelerate degradation of silicate mineral. Earthworms play an important role in ecosystem processe since they not only have some positive effects on soil structure, but also promote nutrient cycling of ecosystem by enhancing the weathering of minerals.

Background • An intertrochanteric fracture can cause ischemic necrosis in the femoral head, leading to negative effects. There are many types of implants for this fracture procedure, including metal-on-metal, metal-onpolyethylene, ceramic-on-ceramic, and ceramic-onpolyethylene, that are currently in use. The current modification is a hybrid prosthetic implant with high functional capacity compared with predecessors. This study aims to determine the procedure’s efficacy in recovery, function restoration, complications, and cost-effectiveness. Methods • Our study used a total of 200 patients undergoing total hip arthroplasty and 135 patients undergoing semi-hip arthroplasty to determine the effectiveness of total hip arthroplasty and femoral head arthroplasty From May 2022 to May 2023. Using the RAOSOFT sampling technique, 132 and 101 in the observation and control group, respectively, the sample is obtained with a confidence interval of 95%, an error margin of 1%, and response interval confidence of 50%. This is a descriptive type of research that relies on a metaanalysis of the available data from PubMed, scholarly articles, and the Chinese biomedical database to gather the fundamental data needed to conduct the research. Data obtained is analyzed using SSPS and STATA and presented in tables showing a summary of the objective measured value. Result • In this study, the Harris joint score of patients in the total hip arthroplasty group was significantly higher than that of the control group, indicating that total hip arthroplasty can restore femoral head function, but still lacks absolute strength like half hip arthroplasty. Conclusions • Femoral head replacement is a complex procedure, but the efficacy in restoring the function is better. In conclusion, despite slow healing and regeneration, the efficacy of complete artificial femoral head replacement is higher in restoring function for various fractures. [ABSTRACT FROM AUTHOR]