Characterization and application of in situ curcumin/ZNP hydrogels for periodontitis treatment.

BACKGROUND: Periodontitis is a chronic inflammatory disease that occurs in tooth-supporting tissues. Controlling inflammation and alleviating periodontal tissue destruction are key factors in periodontal therapy. This study aimed to develop an in situ curcumin/zinc oxide (Cur/ZNP) hydrogel and investigate its characteristics and effectiveness in the treatment of periodontitis. METHODS: Antibacterial activity and cytotoxicity assays were performed in vitro. To evaluate the effect of the in situ Cur/ZNP hydrogel on periodontitis in vivo, an experimental periodontitis model was established in Sprague‒Dawley rats via silk ligature and inoculation of the maxillary first molar with Porphyromonas gingivalis. After one month of in situ treatment with the hydrogel, we examined the transcriptional responses of the gingiva to the Cur/ZNP hydrogel treatment and detected the alveolar bone level as well as the expression of osteocalcin (OCN) and osteoprotegerin (OPG) in the periodontal tissues of the rats. RESULTS: Cur/ZNPs had synergistic inhibitory effects on P. gingivalis and good biocompatibility. RNA sequencing of the gingiva showed that immune effector process-related genes were significantly induced by experimental periodontitis. Carcinoembryonic antigen-related cell adhesion molecule 1 (Ceacam1), which is involved in the negative regulation of bone resorption, was differentially regulated by the Cur/ZNP hydrogel but not by the Cur hydrogel or ZNP hydrogel. The Cur/ZNP hydrogel also had a stronger protective effect on alveolar bone resorption than both the Cur hydrogel and the ZNP hydrogel. CONCLUSION: The Cur/ZNP hydrogel effectively inhibited periodontal pathogenic bacteria and alleviated alveolar bone destruction while exhibiting favorable biocompatibility.

Histone deacetylase inhibitor pracinostat suppresses colorectal cancer by inducing CDK5-Drp1 signaling-mediated peripheral mitofission.

Divisions at the periphery and midzone of mitochondria are two fission signatures that determine the fate of mitochondria and cells. Pharmacological induction of excessively asymmetric mitofission-associated cell death (MFAD) by switching the scission position from the mitochondrial midzone to the periphery represents a promising strategy for anticancer therapy. By screening a series of pan-inhibitors, we identified pracinostat, a pan-histone deacetylase (HDAC) inhibitor, as a novel MFAD inducer, that exhibited a significant anticancer effect on colorectal cancer (CRC) in vivo and in vitro. Pracinostat increased the expression of cyclin-dependent kinase 5 (CDK5) and induced its acetylation at residue lysine 33, accelerating the formation of complex CDK5/CDK5 regulatory subunit 1 and dynamin-related protein 1 (Drp1)-mediated mitochondrial peripheral fission. CRC cells with high level of CDK5 (CDK5-high) displayed midzone mitochondrial division that was associated with oncogenic phenotype, but treatment with pracinostat led to a lethal increase in the already-elevated level of CDK5 in the CRC cells. Mechanistically, pracinostat switched the scission position from the mitochondrial midzone to the periphery by improving the binding of Drp1 from mitochondrial fission factor (MFF) to mitochondrial fission 1 protein (FIS1). Thus, our results revealed the anticancer mechanism of HDACi pracinostat in CRC via activating CDK5-Drp1 signaling to cause selective MFAD of those CDK5-high tumor cells, which implicates a new paradigm to develop potential therapeutic strategies for CRC treatment.

Effects of multiple key factors on the performance of petroleum coke-based constructed wetland-microbial fuel cell.

In this study, two constructed wetland-microbial fuel cells (CW-MFC), including a closed-circuit system (CCW-MFC) and an open-circuit system (OCW-MFC) with petroleum coke as electrode and substrate, were constructed to explore the effect of multiple key factors on their operation performances. Compared to a traditional CW, the CCW-MFC system showed better performance, achieving an average removal efficiency of COD, NH4+-N, and TN of 94.49 ± 1.81%, 94.99 ± 4.81%, and 84.67 ± 5.6%, respectively, when the aeration rate, COD concentration, and hydraulic retention time were 0.4 L/min, 300 mg/L, and 3 days. The maximum output voltage (425.2 mV) of the CCW-MFC system was achieved when the aeration rate was 0.2 L/min. In addition, the CCW-MFC system showed a greater denitrification ability due to the higher abundance of Thiothrix that might attract other denitrifying bacteria, such as Methylotenera and Hyphomicrobium, to participate in the denitrifying process, indicating the quorum sensing could be stimulated within the denitrifying microbial community.

Effects of electroconductive materials on treatment performance and microbial community structure in biofilter systems with silicone tubings.

Biofilter systems coupling with microbial electrochemical technology can enhance the removal performance of pollutants. In this study, two types of coke (PK-A and PK-LSN) were used as electroconductive substrates in biofilter systems with silicone tubings. The results showed that the silicone tubings were beneficial for removing NH4+-N. The PK-A systems reached removal efficiencies up to 83.5-85.3% for NH4+-N without aeration. Compared to gravel systems, significantly higher removal efficiencies of NO3--N (84.8-95.4%) were obtained in coke systems, and better removal of PO43--P (91.9-95.7%) was also simultaneously achieved in PK-A systems. Redundancy analysis (RDA) indicated that the better performances of coke systems rely on the functions of both electroactive (Trichococcus and Sulfurovum) and non-electroactive bacteria (Clostridium_sensu_stricto_1, Propionicicella, and Acinetobacter). These findings highlight the important contribution of silicone tubings to oxygen supply and provide useful guidance for the application of coke in composite matrix systems.

Effect of Leaching Behavior on the Geometric and Hydraulic Characteristics of Concrete Fracture.

The leaching of material from concrete fracture surfaces has an impact on the structural concrete in service, but the number of studies that consider the effect of the coupling of the leaching, fracture geometry and hydraulic processes on concrete fractures is insufficient. In this study, a series of experiments was conducted, and a leaching model proposed, to investigate the mechanism of leaching behavior on the geometric and hydraulic characteristics of concrete fractures. Following the leaching experiment, the evolution of fracture geometric characteristics was observed by a three-dimensional (3D) laser scanning technique, finding that the fracture produces residual leached depth and local uneven leaching, which results in a decrease in roughness. The hydraulic characteristics were then investigated by permeability tests, and it was found that the fracture hydraulic aperture and permeability increase monotonically with leaching time. A simulation of fluid flow in a numerical fracture revealed the effect of residual leached depth and a decrease in roughness on the hydraulic characteristics. Finally, based on the analysis of the chemical composition of the leaching solution, a leaching model of concrete rough fracture surface is proposed and the mechanism of leaching behavior is discussed. These new findings are useful for the understanding of the development of leaching, local to concrete fracture surfaces.

Co-exposures of acid rain and ZnO nanoparticles accelerate decomposition of aquatic leaf litter.

The pattern of acid rain is dependent on the ratio of SO42- and NO3-, which change may affect the dissolution activity of dull heavy metals in the aquatic environment and further complicate the ongoing challenge of ecosystem stability and increase risks. In this study, we assessed the combined effects of acid rain (SO42-: NO3- was 2:1, 1:1, and 1:2) and ZnO nanoparticles (30 ng L-1) on plant litter decomposition through a microcosm experiment. The highest dissolution of ZnO nanoparticles was achieved when the SO42-: NO3- ratio was 1:2, and there were no significant differences among other treatments. The fungal biomass showed significant decreases under acute exposures but tended to be adaptive during chronic exposures. The co-exposure significantly stimulated the activities of leucine-aminopeptidase, glycine-aminopeptidase, polyphenol oxidase, and cellobiohydrolase. Besides, the fungal diversity and the relative abundance of some functional genera (e.g. Anguillospora) were enhanced when the SO42-: NO3- ratio was 1:2 and 2:1. In conclusion, the decomposition rate of plant litter was increased by 123-204% by co-exposures. Collectively, the findings underline the importance of considering environmental context to assess nanoparticle toxicity.

The fungal root endophyte Serendipita vermifera displays inter-kingdom synergistic beneficial effects with the microbiota in Arabidopsis thaliana and barley.

Plant root-associated bacteria can confer protection against pathogen infection. By contrast, the beneficial effects of root endophytic fungi and their synergistic interactions with bacteria remain poorly defined. We demonstrate that the combined action of a fungal root endophyte from a widespread taxon with core bacterial microbiota members provides synergistic protection against an aggressive soil-borne pathogen in Arabidopsis thaliana and barley. We additionally reveal early inter-kingdom growth promotion benefits which are host and microbiota composition dependent. Using RNA-sequencing, we show that these beneficial activities are not associated with extensive host transcriptional reprogramming but rather with the modulation of expression of microbial effectors and carbohydrate-active enzymes.

Nanoplastic pollution inhibits stream leaf decomposition through modulating microbial metabolic activity and fungal community structure.

Many studies have proved the impacts of nanoplastic pollution in freshwaters on aquatic organisms and ecosystems. To explore toxic mechanisms of nanoplastics on stream functioning, we conducted a microcosm experiment to investigate the effects of polystyrene nanoparticles (PS NPs, 1-100 µg L-1) on the process of leaf litter decomposition mediated by the microbial community. The chronic exposure to PS NPs at 1 and 100 µg L-1 caused significant decreases in leaf litter decomposition and nutrient (carbon and nitrogen) releases. During the ecological process, some extracellular enzymes (i.e., ß-glucosidase, glycine-aminopeptidase, and phenol oxidase) rather than fungal biomass were suppressed. Besides, decreases in the relative abundance of Anguillospora and Setophaeosphaeria weakened their functions in leaf litter decomposition. Thus, the microcosm experiment showed that PS NPs inhibited stream leaf decomposition by modulating the microbial metabolic activity and fungal community structure. Overall, the results of this study provide evidence for the consequences of nanoplastic pollution on freshwater microbial community and stream ecosystem functioning, which is conducive to evaluate the potential risks of nanoplastics in aquatic environments.

Staphylococcus aureus Synergized with Candida albicans to Increase the Pathogenesis and Drug Resistance in Cutaneous Abscess and Peritonitis Murine Models.

The mixed species of Staphylococcus aureus and Candida albicans can cause infections on skin, mucosa or bloodstream; however, mechanisms of their cross-kingdom interactions related to pathogenesis and drug resistance are still not clear. Here an increase of S. aureus proliferation and biofilm formation was observed in S. aureus and C. albicans dual-species culture, and the synergistic pathogenic effect was then confirmed in both local (cutaneous abscess) and systemic infection (peritonitis) murine models. According to the transcriptome analysis of the dual-species culture, virulence factors of S. aureus were significantly upregulated. Surprisingly, the beta-lactams and vancomycin-resistant genes in S. aureus as well as azole-resistant genes in C. albicans were also significantly increased. The synergistic effects on drug resistance to both antibacterial and antifungal agents were further proved both in vitro and in cutaneous abscess and peritonitis murine models treated by methicillin, vancomycin and fluconazole. The synergistic interactions between S. aureus and C. albicans on pathogenesis and drug resistance highlight the importance of targeting the microbial interactions in polyspecies-associated infections.

B-Myb accelerates colorectal cancer progression through reciprocal feed-forward transactivation of E2F2.

B-Myb is an important transcription factor that plays a critical role in gene expression regulation and tumorigenesis. However, its functional implication in colorectal cancer remains elusive. In this study, we found that B-Myb was significantly upregulated at both mRNA and protein levels in colorectal cancer samples compared to non-tumor counterparts. B-Myb overexpression accelerated cell proliferation, cell cycle progression and cell motility in colorectal cancer cells, and promoted tumor growth in orthotopic nude mouse models in vivo. In contrast, B-Myb depletion inhibited these malignant phenotypes. Mechanistic investigations revealed that E2F2 was a novel transcriptional target of B-Myb and is essential to B-Myb-induced malignant phenotypes. Notably, B-Myb and E2F2 exhibited positive expression correlation, and interacted with each other in colorectal cancer cells. In addition to their autoregulatory mechanisms, B-Myb and E2F2 can also directly transactivate each other, thus constituting consolidated reciprocal feed-forward transactivation loops. Moreover, both B-Myb and E2F2 are required for the activation of ERK and AKT signaling pathways in colorectal cancer cells. Taken together, our data clarified a critical role for B-Myb in colorectal cancer and unraveled an exquisite mutual collaboration and reciprocal cross regulation between B-Myb and E2F2 that contribute to the malignant progression of human colorectal cancer.

Host preference and invasiveness of commensal bacteria in the Lotus and Arabidopsis root microbiota.

Roots of different plant species are colonized by bacterial communities, that are distinct even when hosts share the same habitat. It remains unclear to what extent the host actively selects these communities and whether commensals are adapted to a specific plant species. To address this question, we assembled a sequence-indexed bacterial culture collection from roots and nodules of Lotus japonicus that contains representatives of most species previously identified using metagenomics. We analysed taxonomically paired synthetic communities from L. japonicus and Arabidopsis thaliana in a multi-species gnotobiotic system and detected signatures of host preference among commensal bacteria in a community context, but not in mono-associations. Sequential inoculation experiments revealed priority effects during root microbiota assembly, where established communities are resilient to invasion by latecomers, and that host preference of commensal bacteria confers a competitive advantage in their cognate host. Our findings show that host preference in commensal bacteria from diverse taxonomic groups is associated with their invasiveness into standing root-associated communities.

Coordination of microbe-host homeostasis by crosstalk with plant innate immunity.

Plants grown in natural soil are colonized by phylogenetically structured communities of microbes known as the microbiota. Individual microbes can activate microbe-associated molecular pattern (MAMP)-triggered immunity (MTI), which limits pathogen proliferation but curtails plant growth, a phenomenon known as the growth-defence trade-off. Here, we report that, in monoassociations, 41% (62 out of 151) of taxonomically diverse root bacterial commensals suppress Arabidopsis thaliana root growth inhibition (RGI) triggered by immune-stimulating MAMPs or damage-associated molecular patterns. Amplicon sequencing of bacterial 16S rRNA genes reveals that immune activation alters the profile of synthetic communities (SynComs) comprising RGI-non-suppressive strains, whereas the presence of RGI-suppressive strains attenuates this effect. Root colonization by SynComs with different complexities and RGI-suppressive activities alters the expression of 174 core host genes, with functions related to root development and nutrient transport. Furthermore, RGI-suppressive SynComs specifically downregulate a subset of immune-related genes. Precolonization of plants with RGI-suppressive SynComs, or mutation of one commensal-downregulated transcription factor, MYB15, renders the plants more susceptible to opportunistic Pseudomonas pathogens. Our results suggest that RGI-non-suppressive and RGI-suppressive root commensals modulate host susceptibility to pathogens by either eliciting or dampening MTI responses, respectively. This interplay buffers the plant immune system against pathogen perturbation and defence-associated growth inhibition, ultimately leading to commensal-host homeostasis.

Depression in patients with epilepsy during the COVID-19 pandemic based on longitudinal self-reporting.

The current study screened major depression in people with epilepsy (PWE) during the epidemic of the novel coronavirus-related disease COVID-19, in order to identify whether the outbreak generated negative psychological impact on PWE. A Chinese version of the Neurological Disorders Depression Inventory for Epilepsy (C-NDDI-E), a self-reporting depression inventory, was applied for rapid detection of major depression. Assessment was carried out online during three different periods (prior to, during, and after the outbreak of COVID-19), with the aim of identifying changes in prevalence of depression and associated risk factors. A total of 158 PWE were recruited into the study (48.7% female). The questionnaire completion rates were 94.3% and 70.9% during and after the outbreak, respectively. The prevalence of depression prior to the epidemic, as the baseline, was 34.8% and increased to 42.3% during the period of the epidemic. Towards the end of the outbreak, the prevalence declined towards the baseline (36.6%). Factors such as living alone (OR = 4.022, 95% CI: 1.158-13.971, P = 0.028) and active seizures before the epidemic (OR = 2.993, 95% CI: 1.197-7.486, P = 0.019) were associated with depression during the epidemic. Monotherapy appeared to be protective against depression (OR = 0. 105, 95% CI: 0.047-0.235, P <0.001). Our results suggest that the pandemic exerts negative influence on PWE's mental health. Depression is one of the common psychological disorders that needs greater attention during this extraordinary period.

Candida albicans CHK1 gene from two-component system is essential for its pathogenicity in oral candidiasis.

The roles of Candida albicans CHK1, a key gene from two-component system, in oral mucosal infection are not clear. This study evaluated the key roles of CHK1 gene in vitro and in vivo. The expression of CHK1 and its regulated virulence factors were tested during the oral epithelial cell infection. The production of lactate dehydrogenase, ROS, and IL-1α combined with the confocal and scanning electron microscope observation was employed to identify the capability of CHK1 in damaging the epithelial cells. Both immunocompetent and immunodeficient mice oropharyngeal infection models were involved to confirm the roles of CHK1 gene in vivo. The expression of CHK1 gene was significantly increased during the oral epithelial cell infection. The chk1Δ/Δ mutant failed to damage the epithelial cells or induce IL-α and ROS production. Interestingly, chk1Δ/Δ can also form the similar hyphae with WT and complementary strains. Accordingly, chk1Δ/Δ did not affect the adhesion and invasion rates of C. albicans to oral epithelial cells. However, chk1Δ/Δ significantly decreased the expression levels of the virulence factors, including ALS2, SAP6, and YWP1. The chk1Δ/Δ also failed to cause oral candidiasis in both immunocompetent and immunodeficient mice indicating that CHK1 gene from the two-component system is essential for the pathogenicity of C. albicans. KEY POINTS: • CHK1gene is essential for C. albicans in oral candidiasis • C. albicans without CHK1 gene can form "non-pathogenic" hyphae. • CHK1 gene regulates the virulence of C. albicans.

Hsa-miR-335 enhances cell migration and invasion in lung adenocarcinoma through targeting Copine-1.

Lung adenocarcinoma (LAC) is one of the most common pulmonary adenocarcinomas with a high peak of mortality, and metastasis is the main culprit of LAC deaths. microRNAs play important role in cancer metastasis, and thus are regarded as potential diagnostic and prognostic markers for human cancers. However, many miRNAs exhibit dual roles in diverse cellular contexts. Here, we revealed that hsa-miR-335, a previously reported tumor suppressor, exhibited an oncogenic role in LAC. Overexpression of miR-335 enhanced the abilities of A549 and H1299 cells to invade and migrate by regulating epithelial-mesenchymal transition, while inhibition of miR-335 exhibited an opposite effect in vitro and in vivo. Mechanically, miR-335 inhibited the expression of Copine-1 (CPNE1), an NF-κB suppressor, through interacting with its mRNA 3'UTR, while mutating the binding sites abolished this inhibitory effect. This finding not only highlights the suppressive effect of CPNE1 on cell motility, but also provides new insight into miR-335 in promoting LAC metastasis.

Epilepsy management during epidemic: A preliminary observation from western China.

OBJECTIVE: This study aimed to investigate whether the proposed model could manage patients with epilepsy (PWEs) during the coronavirus disease 2019 (COVID-19) outbreak. METHODS: We used a model to manage the PWEs during the outbreak. Questionnaire survey and hospital data were used to explore whether PWEs under our management were affected by the virus. RESULTS: A total of 118 (78.7%) PWEs completed the survey. During the "model period," 22.9% (27/118) of the respondents reported antiepileptic drug (AEDs) discontinuity, including six (22.2%) PWEs who failed to purchase AEDs. Of the patients, 40.7% (22/54) failed to attend ordinary clinic, which was higher than that during the "period before model" (7.9%, 5/63). The common causes were movement limits (77.3%) and appointment failure (54.5%). A shift from ordinary clinic toward remote consultation was observed. Of the PWEs, 15.7% (13/83) referred to online pharmacy. 87.5% (14/16) of emergencies related to epilepsy were timely treated. 48.3%of PWEs thought that the epidemic had an impact on accessing medical services. Hospital data indicated that a decline in ordinary clinic visit, inpatient, surgery, and emergency attendance was observed in January and February 2020 and an increase in March 2020, as the epidemic mitigated. By contrast, online clinic visit soared in February, when the outbreak hit hard. In addition, we found no cross-infection of COVID-19 in our hospital and respondents. CONCLUSION: We demonstrated a much-needed model to manage the PWEs during the outbreak. We believed that the core architecture of this model was suitable for the management of other chronic diseases.

Biochanin A alleviates gingival inflammation and alveolar bone loss in rats with experimental periodontitis.

Biochanin A (BA) is an organic compound produced by Trifolium pretense and Arachis hypogaea with anti-inflammatory and antioxidative effects. The aim of the current study was to evaluate the effects of BA on gingival inflammation and alveolar bone destruction in rats with experimental periodontitis. Experimental rats (n=25) were distributed equally into five groups: i) Healthy control (control) group; ii) experimental periodontitis (ligation) group; and iii) and ligation plus low, medium and high dose of BA (12.5, 25 and 50 mg/kg/day, respectively) groups. A nylon ligature was inserted around rats' maxillary molars for 14 days to trigger the experimental periodontitis. BA was intravenous injected once daily for 4 weeks. After that, interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), reactive oxygen species (ROS) and osteocalcin (OCN) levels were determined in gingival and/or serum samples using ELISA or reverse transcription-quantitative PCR. Alveolar bone volume was assessed via hematoxylin and eosin staining and micro-computed tomography. Osteoclasts were identified by tartrate-resistant acid phosphatase staining, and the level of the nuclear factor erythroid-2 related factor 2 (Nrf2) was also detected by immunohistochemical staining. BA treatment groups showed alleviated alveolar bone resorption compared with the ligation group. Moreover, BA treatment significantly inhibited IL-1ß, TNF-α, ROS levels, and reduced leukocyte acid phosphatase-positive cells, as well as increased OCN and Nrf2 levels compared with the ligation group. BA had beneficial effects on experimental periodontitis of rats. BA treatment inhibited inflammation, regulated unbalanced oxidative stress response and ameliorated the alveolar bone loss.

Root-Secreted Coumarins and the Microbiota Interact to Improve Iron Nutrition in Arabidopsis.

Plants benefit from associations with a diverse community of root-colonizing microbes. Deciphering the mechanisms underpinning these beneficial services are of interest for improving plant productivity. We report a plant-beneficial interaction between Arabidopsis thaliana and the root microbiota under iron deprivation that is dependent on the secretion of plant-derived coumarins. Disrupting this pathway alters the microbiota and impairs plant growth in iron-limiting soil. Furthermore, the microbiota improves iron-limiting plant performance via a mechanism dependent on plant iron import and secretion of the coumarin fraxetin. This beneficial trait is strain specific yet functionally redundant across phylogenetic lineages of the microbiota. Transcriptomic and elemental analyses revealed that this interaction between commensals and coumarins promotes growth by relieving iron starvation. These results show that coumarins improve plant performance by eliciting microbe-assisted iron nutrition. We propose that the bacterial root microbiota, stimulated by secreted coumarins, is an integral mediator of plant adaptation to iron-limiting soils.

Optimising epilepsy management with a smartphone application: a randomised controlled trial.

OBJECTIVE: To assess whether a practical intervention based upon a smartphone application (app) would improve self-management and seizure control in adults with epilepsy. DESIGN, SETTING: Randomised, controlled trial in western China, December 2017 to August 2018. PARTICIPANTS: 380 eligible people with epilepsy were recruited; 327 completed the 6-month follow-up (176 in the app group, 151 in the control group). MAIN OUTCOME MEASURES: Self-management of epilepsy (measured with the validated Chinese Epilepsy Self-Management Scale, C-ESMS) and self-reported seizure frequency. RESULTS: In the intention-to-treat analysis, the mean C-ESMS score increased significantly in the app group between baseline and the 6-month evaluation (from 121.7 [SD, 12.1] to 144.4 [SD, 10.0]; P < 0.001); improvements on the information management, medication management, and safety management subscales were also statistically significant. At 6 months, the mean overall C-ESMS score for the app group was significantly higher than that for the control group (125.4 [SD, 1.5];  P < 0.001). The proportion of patients who were seizure-free at the 6-month follow-up was larger for the app than the control group (54 of 190, 28% v 22 of 190, 12%), as was the proportion with reductions in frequency of between 75 and 100% (22 of 190, 12% v 8 of 190, 4%). Changes in C-ESMS score were not statistically associated with seizure frequency. CONCLUSIONS: Using a smartphone app improved epilepsy self-management scores in people in western China. It should be further tested in larger populations in other areas. Our preliminary investigation of building digital communities for people with epilepsy should encourage similar approaches to managing other chronic diseases. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900026864, 24 October 2019.