EPO promotes the progression of rheumatoid arthritis by inducing desialylation via increasing the expression of neuraminidase 3.

OBJECTIVE: Erythropoietin (EPO) known as an erythrocyte-stimulating factor is increased in patients with rheumatoid arthritis (RA). Nevertheless, the function of EPO in the process of RA and relative mechanism needs to be further clarified. METHODS: The level of EPO in serum and synovial fluid from patients with RA and healthy controls was determined by . Collagen-induced arthritis (CIA) mice were constructed to confirm the role of EPO on RA pathogenesis. Differentially expressed genes (DEGs) of EPO-treated fibroblast-like synoviocyte (FLS) were screened by transcriptome sequencing. The transcription factor of neuraminidase 3 (NEU3) of DEGs was verified by double luciferase reporting experiment, DNA pulldown, electrophoretic mobility shift assay and chromatin immunoprecipitation-quantitative PCR (qPCR) assay. RESULTS: The overexpression of EPO was confirmed in patients with RA, which was positively associated with Disease Activity Score 28-joint count. Additionally, EPO intervention could significantly aggravate the joint destruction in CIA models. The upregulation of NEU3 was screened and verified by transcriptome sequencing and qPCR in EPO-treated FLS, and signal transducer and activator of transcription 5 was screened and verified to be the specific transcription factor of NEU3. EPO upregulates NEU3 expression via activating the Janus kinase 2 (JAK2)-STAT5 signalling pathway through its receptor EPOR, thereby to promote the desialylation through enhancing the migration and invasion ability of FLS, which is verified by JAK2 inhibitor and NEU3 inhibitor. CONCLUSION: EPO, as a proinflammatory factor, accelerates the process of RA through transcriptional upregulation of the expression of NEU3 by JAK2/STAT5 pathway.

CCCTC-binding factor: the specific transcription factor of ß-galactoside α-2,6-sialyltransferase 1 that upregulates the sialylation of anti-citrullinated protein antibodies in rheumatoid arthritis.

OBJECTIVE: Sialylation of the crystallizable fragment (Fc) of ACPAs, which is catalysed by ß-galactoside α-2,6-sialyltransferase 1 (ST6GAL1) could attenuate inflammation of RA. In this study, we screened the transcription factor of ST6GAL1 and elucidated the mechanism of transcriptionally upregulating sialylation of ACPAs in B cells to explore its role in the progression of RA. METHODS: Transcription factors interacting with the P2 promoter of ST6GAL1 were screened by DNA pull-down and liquid chromatography with tandem mass spectrometry (LC-MS/MS), and verified by chromatin immunoprecipitation (ChIP), dual luciferase reporter assay and electrophoretic mobility shift assay (EMSA). The function of the CCCTC-binding factor (CTCF) on the expression of ST6GAL1 and the inflammatory effect of ACPAs were verified by knocking down and overexpressing CTCF in B cells. The CIA model was constructed from B cell-specific CTCF knockout mice to explore the effect of CTCF on arthritis progression. RESULTS: We observed that the levels of ST6GAL1 and ACPAs sialylation decreased in the serum of RA patients and were negatively correlated with DAS28 scores. Subsequently, CTCF was screened and verified as the transcription factor interacting with the P2 promoter of ST6GAL1, which enhances the sialylation of ACPAs, thus weakening the inflammatory activity of ACPAs. Furthermore, the above results were also verified in the CIA model constructed from B cell-specific CTCF knockout mice. CONCLUSION: CCCTC-binding factor is the specific transcription factor of ß-galactoside α-2,6-sialyltransferase 1 in B cells that upregulates the sialylation of ACPAs in RA and attenuates the disease progression.

PbBeB2O5: A High-Performance Ultraviolet Nonlinear-Optical Crystal with Functional [BeB2O8]8- Group.

High-performance nonlinear-optical (NLO) crystals need to simultaneously meet multiple basic and conflicting performance requirements. Here, by using a partial chemical substitution strategy, the first noncentrosymmetric (NCS) PbBeB2O5 crystal with a BeB2O8 group was synthesized, exhibiting a two-dimensional [BeB2O5]∞ layer constructed by interconnecting BeB2O8 groups and bridged PbO4 with an active lone pair. The crystal shows a promising UV NLO functional feature, including a strong SHG effect of 3.5 × KDP (KH2PO4), large birefringence realizing phase matchability in the whole transparency region from 246 to 2500 nm, a short UV absorption edge of 246 nm, and single-crystal easy growth. Remarkably, theoretical studies reveal that the BeB2O8 group has high nonlinear activity, which could stimulate the discovery of a series of excellent NLO beryllium borates.

A fully human connective tissue growth factor blocking monoclonal antibody ameliorates experimental rheumatoid arthritis through inhibiting angiogenesis.

BACKGROUND: Connective tissue growth factor (CTGF) plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA) by facilitating angiogenesis and is a promising therapeutic target for RA treatment. Herein, we generated a fully human CTGF blocking monoclonal antibody (mAb) through phage display technology. RESULTS: A single-chain fragment variable (scFv) with a high affinity to human CTGF was isolated through screening a fully human phage display library. We carried out affinity maturation to elevate its affinity for CTGF and reconstructed it into a full-length IgG1 format for further optimization. Surface plasmon resonance (SPR) data showed that full-length antibody IgG mut-B2 bound to CTGF with a dissociation constant (KD) as low as 0.782 nM. In the collagen-induced arthritis (CIA) mice, IgG mut-B2 alleviated arthritis and decreased the level of pro-inflammatory cytokines in a dose-dependent manner. Furthermore, we confirmed that the TSP-1 domain of CTGF is essential for the interaction. Additionally, the results of Transwell assays, tube formation experiments, and chorioallantoic membrane (CAM) assays showed that IgG mut-B2 could effectively inhibit angiogenesis. CONCLUSION: The fully human mAb that antagonizes CTGF could effectively alleviate arthritis in CIA mice, and its mechanism is tightly associated with the TSP-1 domain of CTGF.

Agomir miRNA-150-5p alleviates pristane-induced lupus by suppressing myeloid dendritic cells activation and inflammation via TREM-1 axis.

OBJECTIVE: Triggering receptors expressed on myeloid cells-1 (TREM-1) has been shown to participate in inflammatory autoimmune diseases. Nevertheless, the detailed underlying mechanisms and therapeutic benefits by targeting TREM-1 remain elusive, especially in myeloid dendritic cells (mDCs) and systemic lupus erythematosus (SLE). Disorders of epigenetic processes including non-coding RNAs give rise to SLE, resulting in complicated syndromes. Here, we aim to address this issue and explore the miRNA to inhibit the activation of mDCs and alleviate the progress of SLE by targeting TREM-1 signal axis. METHODS: Bioinformatics methods were used to analyze the differentially expressed genes (DEGs) between patients with SLE and healthy individuals by four mRNA microarray datasets from Gene Expression Omnibus (GEO). Then we identified the expression of TREM-1 and its soluble form (sTREM-1) in clinical samples by ELISA, quantitative real-time PCR and Western blot. Phenotypic and functional changes of mDCs elicited by TREM-1 agonist were determined. Three databases of miRNAs target prediction and a dual-luciferase reporter assay were used to screen and verify miRNAs that can directly inhibit TREM-1 expression in vitro. Moreover, pristane-induced lupus mice were injected with miR-150-5p agomir to evaluate the effects of miR-150-5p on mDCs in lymphatic organs and disease activity in vivo. RESULTS: We screened TREM-1 as one of the hub genes closely correlated with the progression of SLE and identified sTREM-1 in serum as a valuable diagnostic biomarker for SLE. Moreover, activation of TREM-1 by its agonist promoted activation and chemotaxis of mDCs and increased the production of inflammatory cytokines and chemokines, showing higher expression of IL-6, TNF-α, and MCP-1. We showed that lupus mice displayed a unique miRNA signature in spleen, among which miR-150 was the most significantly expressed miRNA that targeting TREM-1 compared with wild type group. Transfection of miRNA-150-5p mimics directly suppressed the expression of TREM-1 by binding to its 3' UTR. Our in vivo experiments first indicated that administration of miR-150-5p agomir effectively ameliorated lupus symptoms. Intriguingly, miR-150 inhibited the over activation of mDCs through TREM-1 signal pathway in lymphatic organs and renal tissues. CONCLUSIONS: TREM-1 represents a potentially novel therapeutic target and we identify miR-150-5p as one of the mechanisms to alleviate lupus disease, which is attributable for inhibiting mDCs activation through TREM-1 signaling pathway.

First Report of Clover yellow vein virus Infecting Senna septemtrionalis (Arsenic bush).

Clover yellow vein virus (ClYVV) is a member of the genus Potyvirus, family Potyviridae and was reported to infect many plant species, such as Ammi majus L., Phaseolus vulgaris L., Vicia faba L., Lens culinaris L., Borago officinalis L., Cicer arietinum L., Gladiolous gandavensis L., Glycine max L., Trifolium repens L., and Dendrobium sp. (Irey et al. 2006; Ortiz et al. 2009; Park et al. 2014; Yoon et al. 2022). Senna septemtrionalis (Viv.) H.S.Irwin & Barneby (arsenic bush), a species in the subfamily Caesalpinioideae, is widely distributed in tropical and subtropical regions (Datiles et al. 2022). In June 2021, virus-like symptoms of mosaic, chlorosis, and leaf-curling were observed in arsenic bush in Kunming, Yunnan province, China. Symptomatic leaves were collected from four arsenic bush (SS1-4), and asymptomatic leaves were collected from 3 additional arsenic bush plants (SS5-7) (eXtra S1). To identify the putative causal virus, sap of symptomatic leaves (SS1) was stained with 1 % phosphotungstic acid and observed under a transmission electron microscope (TEM). Potyvirus-like particles (about 750-800 nm  13 nm) were observed from the sample (eXtra S1). Total RNA was extracted from sample SS1 using TRIzol Reagent (Invitrogen, USA) and subjected to the Illumina NovaSeq platform for RNA-Seq. After trimming and quality control of raw data, 24,125,963 high-quality clean reads were assembled into 72,835 Unigenes using Trinity software. BLAST searches indicated that the nucleotide sequence of Unigene c29731 (10,893 nt) and its deduced amino acid sequence shared 82.62% to 96.45% and 92.60% to 99.19% identity with several ClYVV isolates, respectively. Unigene c29731 had the highest coverage ratio (88%) and the highest nucleotide sequence identity (96.45%) with ClYVV isolate IA-2016 (GenBank accession No. MK292120.1). The complete genome of ClYVV SS1 isolate (ClYVV-SS, GenBank accession No. OP868578) was determined using RT-PCR and 5' and 3' rapid amplification of cDNA ends (RACE) (Chen et al. 2001). A total of 224,936 out of 24,125,963 reads were mapped to the ClYVV-SS1 genome, yielding an average depth of coverage of 3,056.823 (min=1, max=7,859) at nucleotides from 1 to 9,324 of ClYVV genome (eXtra S2). BLASTN results indicated that the complete genome of ClYVV-SS1 shared 96.45% nucleotide sequence identity and 99% coverage ratio with ClYVV isolate IA-2016 genome. Phylogenetic analysis showed that ClYVV-SS1 and other ClYVV isolates clustered together (eXtra S2). RT-PCR was performed on samples (SS2-7) using a pair of primers of the coat protein gene (5'- TCCGACAAAGATAAGTTGAATGCTGGTG-3' and 5'-GAATCGTGCTCCAGCAATGTGA-3') designed from multiple sequences alignment (MSA). Using SS1 sample as positive control, amplicons of ~813 bp were obtained from three symptomatic samples (SS2-4) but not the asymptomatic ones (SS5-7). A total of 17 of 20 arsenic bushes developed symptoms of mosaic and leaf-curling approximately two weeks after mechanical inoculation with arsenic bush (SS1) sap, with 10 uninoculated plants used as control (eXtra S1). RT-PCR was performed for all tested plants. 17 symptomatic arsenic bushes tested positive for ClYVV, while all other samples tested negative. This confirmed that the symptomatic arsenic bushes were infected with ClYVV. To our knowledge, this is the first report of ClYVV infecting arsenic bush.

Polyethylene glycol crosslinked decellularized single liver lobe scaffolds with vascular endothelial growth factor promotes angiogenesis in vivo.

BACKGROUND: Improving the mechanical properties and angiogenesis of acellular scaffolds before transplantation is an important challenge facing the development of acellular liver grafts. The present study aimed to evaluate the cytotoxicity and angiogenesis of polyethylene glycol (PEG) crosslinked decellularized single liver lobe scaffolds (DLSs), and establish its suitability as a graft for long-term liver tissue engineering. METHODS: Using mercaptoacrylate produced by the Michael addition reaction, DLSs were first modified using N-succinimidyl S-acetylthioacetate (SATA), followed by cross-linking with PEG as well as vascular endothelial growth factor (VEGF). The optimal concentration of agents and time of the individual steps were identified in this procedure through biomechanical testing and morphological analysis. Subsequently, human umbilical vein endothelial cells (HUVECs) were seeded on the PEG crosslinked scaffolds to detect the proliferation and viability of cells. The scaffolds were then transplanted into the subcutaneous tissue of Sprague-Dawley rats to evaluate angiogenesis. In addition, the average number of blood vessels was evaluated in the grafts with or without PEG at days 7, 14, and 21 after implantation. RESULTS: The PEG crosslinked DLS maintained their three-dimensional structure and were more translucent after decellularization than native DLS, which presented a denser and more porous network structure. The results for Young's modulus proved that the mechanical properties of 0.5 PEG crosslinked DLS were the best and close to that of native livers. The PEG-VEGF-DLS could better promote cell proliferation and differentiation of HUVECs compared with the groups without PEG cross-linking. Importantly, the average density of blood vessels was higher in the PEG-VEGF-DLS than that in other groups at days 7, 14, and 21 after implantation in vivo. CONCLUSIONS: The PEG crosslinked DLS with VEGF could improve the biomechanical properties of native DLS, and most importantly, their lack of cytotoxicity provides a new route to promote the proliferation of cells in vitro and angiogenesis in vivo in liver tissue engineering.

Glycine increased ferroptosis via SAM-mediated GPX4 promoter methylation in rheumatoid arthritis.

OBJECTIVE: Over-proliferation of synovium is a key event of invasive pannus formation and cartilage damage in the progression of RA disease. At the same time, ferroptosis may play a pivotal role in maintaining the balance of proliferation and death of synovium. In this study, we firstly evaluated the ferroptosis level in RA fibroblast-like synoviocytes (FLS) and then explored the role of glycine in ferroptosis. METHODS: Ferroptosis was evaluated in RA synovium and FLS. The therapeutic effect of glycine on RA was evaluated by clinical and histopathological score and cytokine level in a CIA mouse model. The influence of glycine on ferroptosis was evaluated by mitochondrial morphology observation and membrane potential assay in RA FLS. Methylase expression was detected to explore the mechanism behind the effect of glycine on glutathione peroxidase 4 (GPX4) methylation. RESULTS: Compared with healthy controls, ferroptosis decreased in the RA synovium and FLS, with a decrease in Acyl Coenzyme A Synthetase Long Chain 4 (ACSL4) and an increase in Ferritin heavy chain 1 (FTH1), GPX4 and cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11). Although both oxidation and antioxidation levels of lipids were higher in RA FLS than in healthy controls, the increase in antioxidation was slightly higher than oxidation. RNA-seq and verification showed that glycine regulated the ferroptosis pathway through increase S-adenosylmethionine (SAM) concentration and decrease the expression of GPX4 and FTH1 by promoting SAM-mediated GPX4 promoter methylation and reducing FTH1 expression in RA FLS. CONCLUSIONS: In summary, we confirmed a decline in ferroptosis in RA and explored that glycine enhanced ferroptosis via SAM-mediated GPX4 promoter methylation and ferritin decrease.

Atractylenolide II inhibits tumor-associated macrophages (TAMs)-induced lung cancer cell metastasis.

OBJECTIVE: M2-like tumor-associated macrophages (TAMs) play a crucial role in promoting tumor proliferation, angiogenesis, and metastasis. In the current study, we investigated the relationship between macrophage polarization and the antitumor effect of Atractylenolide II (AT-II) in lung cancer cells. MATERIALS AND METHODS: Cell viability, migration, and invasion were determined by MTT assay, wound healing assay, and transwell assay, respectively. Flow cytometry analysis showed the percentage of CD206+ cells. Gene expression was determined by real-time PCR, western blotting, and immunofluorescence staining. Lewis lung carcinoma mouse xenograft and metastasis models were used to examine the effects of AT-II on lung cancer in vivo. RESULTS: AT-II (2.5 and 5 µM) did not cause significant inhibition of A549 cell viability but markedly inhibited IL-4/IL-13-induced M2-like polarization, evidenced by the decreased expression of the M2 surface marker CD206, down-regulation of specific M2-marker genes (Arg-1, IL-10 and TGF-ß) as well as inhibition of M2 macrophages-mediated invasion and migration of A549 cells. In addition, AT-II inhibited IL-4/IL-13-induced activation of the STAT6 signaling pathway that is vital in the M2-like polarization of macrophages. In animal models, administration of AT-II (50 mg kg-1, i.g., QD for 21 days) significantly inhibited tumor growth, reduced pulmonary metastatic nodules, and down-regulated the percentages of M2 macrophages (F4/80+ and CD206+) in total macrophages (F4/80+) in tumor tissues and pulmonary metastatic nodules. CONCLUSIONS: AT-II effectively inhibits M2-like polarization, thereby inhibiting lung cancer cell metastasis both in vivo and in vitro, revealing a novel potential strategy for the antitumor effect of AT-II.

Application of an L-shaped anterolateral thigh flap in reconstruction after hemiglossectomy.

OBJECTIVE: Tongue defect reconstruction is one of the key components of tongue cancer surgery. In this study, we used an L-shaped flap design adopted as a simple and efficient method to repair tongue defects after hemiglossectomy. Furthermore, we evaluated and contrasted the clinical effects of two methods, the L-shaped and traditional methods. STUDY DESIGN: Fifteen patients in the L-shaped group and 20 patients in the traditional group were evaluated and compared in terms of postoperative complications, dysphagia, language function and appearance satisfaction. RESULTS: The results (Table 1) showed that there were 2 cases of donor area invalid traumas, and 2 patients had scar hyperplasia in the traditional group. The degree of global and functional dysphagia of the L-shaped group (2.60 ± 0.29 and 11.47 ± 1.38) was lower than that of the traditional group (3.55 ± 0.29 and 15.75 ± 1.22) (P < 0.05). In the language evaluation, the traditional group (3.20 ± 0.26) had lower scores than the L-shaped group (4.13 ± 0.30) (P < 0.05). CONCLUSION: The L-shaped ALTP flap is a simple and efficient modification of ALTP, that can be used for half-tongue repair after radical operations for tongue cancer. It has better performance in the recovery of dysphagia and language function than the traditional ALTP flap.

TSP1 is the essential domain of SEMA5A involved in pannus formation in rheumatoid arthritis.

OBJECTIVE: In this study, we explored the effect of semaphorin5A (SEMA5A) on RA pathogenesis and its specific TSP1 domain on pannus formation. METHODS: The expression of SEMA5A was detected in the synovium, the fibroblast-like synoviocytes (FLSs) and the SF of RA patients and healthy controls (HCs) by real-time quantitative PCR (q-PCR), immunohistochemistry staining, western blot and ELISA. SEMA5A-mAb intervention was performed to appraise the severity of joints in the CIA model. Transcriptome sequencing and bioinformatics analysis in SEMA5A-transfected FLSs from HCs were performed to screen differentially expressed genes after SEMA5A overexpression. An MTT assay in RA-FLSs, a chicken embryo allantoic membrane experiment and a tube formation experiment were used to clarify the influence of SEMA5A on cell proliferation and angiogenesis. Furthermore, a rescue experiment verified the function of the TSP1 domain of SEMA5A in the progress of RA with Sema5a-/- CIA mice. RESULTS: The expression of SEMA5A increased in RA compared with that in HCs. Simultaneously, SEMA5A-mAbs significantly attenuated joint injury and the inflammatory response in CIA models. In addition, transcriptome sequencing and angiogenesis-related experiments verified the ability of SEMA5A to promote FLS proliferation and angiogenesis. Moreover, TSP1 was proved to be an essential domain in SEMA5A-induced angiogenesis in vitro. Additionally, rescue of TSP1-deleted SEMA5A failed to reduce the severity of arthritis in a CIA model constructed with Sema5a -/- mice. CONCLUSION: In summary, upregulation of SEMA5A was first confirmed in pathological lesions of RA patients. Furthermore, treatment with SEMA5A-mAbs attenuated the progress of RA in the CIA model. Moreover, TSP1 was indicated as the key domain of SEMA5A in the promotion of pannus formation in RA.

Penicillium chrysogenum polypeptide extract protects tobacco plants from tobacco mosaic virus infection through modulation of ABA biosynthesis and callose priming.

The polypeptide extract of the dry mycelium of Penicillium chrysogenum (PDMP) can protect tobacco plants from tobacco mosaic virus (TMV), although the mechanism underlying PDMP-mediated TMV resistance remains unknown. In our study, we analysed a potential mechanism via RNA sequencing (RNA-seq) and found that the abscisic acid (ABA) biosynthetic pathway and ß-1,3-glucanase, a callose-degrading enzyme, might play an important role in PDMP-induced priming of resistance to TMV. To test our hypothesis, we successfully generated a Nicotiana benthamiana ABA biosynthesis mutant and evaluated the role of the ABA pathway in PDMP-induced callose deposition during resistance to TMV infection. Our results suggested that PDMP can induce callose priming to defend against TMV movement. PDMP inhibited TMV movement by increasing callose deposition around plasmodesmata, but this phenomenon did not occur in the ABA biosynthesis mutant; moreover, these effects of PDMP on callose deposition could be rescued by treatment with exogenous ABA. Our results suggested that callose deposition around plasmodesmata in wild-type plants is mainly responsible for the restriction of TMV movement during the PDMP-induced defensive response to TMV infection, and that ABA biosynthesis apparently plays a crucial role in PDMP-induced callose priming for enhancing defence against TMV.

A potyvirus isolated from Mirabilis jalapa in China represents a new species.

We previously reported a possible potyvirus isolated from Mirabilis jalapa that exhibited a high degree of sequence similarity to Basella rugose mosaic virus (BaRMV) in the region encoding the coat protein (CP). Here, we present the complete genome sequence of this isolate, comprising a 9666-nucleotide-long monopartite ssRNA (excluding the poly(A) tail) encoding a 3080-amino-acid polyprotein. The CP region showed a high degree of nucleotide sequence similarity to three BaRMV isolates (75.2-77.3% identity), while other regions showed nucleotide sequence identity values (48.8-73.7%) below the species demarcation threshold proposed by the ICTV. Therefore, we propose that this isolate be considered a new member of the genus Potyvirus, tentatively named "mirabilis crinkle mosaic virus" (MiCMV).

Effects of different carbon sources on 2,4,6-trichlorophenol degradation in the activated sludge process.

The effects of different carbon sources on the enrichment of 2,4,6TCP-degrading microbes and on reactor stability were was investigated using a lab-scale sequencing batch reactor (SBR). Glucose, sucrose, and starch were selected as different carbon sources because of the different molecular weights. The sucrose-fed activated sludge (AS) exhibited faster adaption and higher degradation rates for 2,4,6-TCP in long-term operation and typical cycles compared to that fed with glucose and starch. Large amounts of extracellular polymeric substance (EPS; 117.54 mg/gVSS) were induced from AS after adding starch, leading to a high SVI (191 mL/g) and poor sludge settling. This suggests that macromolecular carbon sources might have a detrimental effect on the reactor operation. Moreover, the high removal efficiency for TOC and chloride ions was achieved in a typical cycle of all SBRs, indicating that AS could completely mineralize 2,4,6-TCP. On average, more than 90% of the COD could be removed in all SBRs during long-term operation. Glucose, sucrose, and starch facilitated the development of a different microbial community compared to the seeding sludge, making Chloroflexi, Actinobacteria, and Proteobacteria the dominant phylum in the corresponding SBR. The microbial abundance associated with the metabolism of 2,4,6-TCP reached 81.02% due to the addition of sucrose. The results of this study could provide a potential guide for the effective selection of carbon sources in the treatment of chlorophenol wastewater.

Theoretical Study of Hydrogen Storage on Ti-Decorated BC3 Nanostructures.

Hydrogen storage on Ti-decorated BC3 nanosheet and nanotube have been studied using density functional theory (DFT) calculations. It is found that Ti atoms can stably adsorb on the pristine BC3 sheet and nanotube without the problem of clustering. The hybridization between Ti d-orbital and BC3 p-orbital is observed around the Fermi level. From H2 saturation adsorption calculations, we find that each Ti atom can bind up to four hydrogen molecules on the Ti-decorated BC3 sheet and (5, 0) nanotube, yielding the same hydrogen storage capacity of 8.2 wt%. Due to the curvature effect of nanotube, the interaction of hydrogen molecules with Ti@BC3 nanotube is stronger than that of Ti@BC3 sheet. The charge transfers between H2 molecules and Ti atom as well as Ti and BC3 nanostructures are carefully examined.

The Mammalian Target of Rapamycin-70-kDa Ribosomal Protein S6 Kinase Axis Inhibits the Biological Function of Tongue Squamous Cell Carcinoma.

PURPOSE: Studies have shown the mammalian target of rapamycin (mTOR) and 70-kDa ribosomal protein S6 kinase (p70S6K) to be tumor suppressors in many cancers. These factors may have synergistic functions in tongue squamous cell carcinoma (TSCC), which is the most common malignant cancer in the oral region. We aimed to investigate the expression of the mTOR-p70S6K axis in TSCC patients and its biological function in TSCC cell lines. MATERIALS AND METHODS: Sixty-eight TSCC patients were included in this study, and their features, including age, gender, tumor differentiation, lymphatic metastasis, and clinical stage, were recorded. The expression of mTOR and p70S6K was detected by immunohistochemistry. Small interfering RNA constructs were delivered into TSCC cells to downregulate mTOR and p70S6K expression in vitro. After transfection, cell proliferation, migration or invasion, apoptosis, and chemoresistance assays were performed to examine cellular variations of biological function. RESULTS: High expression of the mTOR-p70S6K axis was associated with higher tumor stage, lymph node metastasis, and poor tumor differentiation. Suppression of mTOR and p70S6K in TSCC cells resulted in the inhibition of cell proliferation, metastases, and chemoresistance. Inhibiting mTOR expression could inhibit p70S6K expression but not vice versa. CONCLUSIONS: The high expression of mTOR and p70S6K is closely associated with malignant characterization of TSCC patients, and it could inhibit biological functions of TSCC cell lines. Taken together, the mTOR-p70S6K axis may serve as a potential therapeutic strategy for TSCC.

Acclimation of 2-chlorophenol-biodegrading activated sludge and microbial community analysis.

Using glucose as cosubstrate, activated sludge that could effectively biodegrade 40 mg/L 2-chlorophenol was successfully domesticated in sequencing batch reactors. To acclimate the sludge, 2-chlorophenol was increased stepwise from 0 to 40 mg/L. High-throughput sequencing revealed that the microbial community richness increased during the first 5 days of acclimation to 5 mg/L 2-chlorophenol and then decreased after another 20 days as 2-chlorophenol was increased. The original sludge obtained from a water resource recovery facility had the highest microbial diversity. As the acclimation continued further, community richness and diversity both increased, but they decreased again, significantly, when 2-chlorophenol reached 40 mg/L. Saccharibacteria_norank, Bacillus, Saprospiraceae_uncultured, and Lactococcus were the dominant bacteria. Bacillus and Pseudomonas were the main known chlorophenol-degrading bacteria. WCHB1-60_norank, Tetrasphaera, Comamonadaceae_unclassified, and Haliangium showed poor tolerance to 2-chlorophenol. Higher bacterial tolerance to chlorophenols does not mean higher degrading capability. The degradation of chlorophenols was not positively correlated with the detected abundance of known 2-chlorophenol-degrading bacteria. PRACTITIONER POINTS: Activated sludge that could effectively biodegrade 40 mg/L 2-chlorophenol was successfully domesticated using glucose as cosubstrate in sequencing batch reactors. Saccharibacteria_norank, Bacillus, Saprospiraceae_uncultured, and Lactococcus were the dominant bacteria. Bacillus and Pseudomonas were the main known chlorophenol-degrading bacteria detected in this study. The degrading capability and tolerance of bacteria to chlorophenols were relatively independent and the degradation of chlorophenols may be the synergistic effect of various bacteria.

Maresin 1 improves the Treg/Th17 imbalance in rheumatoid arthritis through miR-21.

OBJECTIVE: Treg/Th17 imbalance plays an important role in rheumatoid arthritis (RA). Maresin 1 (MaR1) prompts inflammation resolution and regulates immune responses. We explored the effect of MaR1 on RA progression and investigated the correlation between MaR1 and Treg/Th17 balance. METHODS: Both patients with RA and healthy controls were recruited into the study. Collagen-induced arthritis (CIA) model was constructed to detect the clinical score, histopathological changes and Treg/Th17 ratio. Purified naive CD4+ T-cells were used to study the effect of MaR1 on its differentiation process and microRNA microarray studies were performed to investigate MaR1 downstream microRNAs in this process. MicroRNA transfection experiments were conducted by lentivirus to verify the mechanism of MaR1 on Treg/Th17 balance. RESULTS: Compared with controls, the MaR1 concentration was higher in the patients with inactive RA and lower in the patients with active RA. Expression of the Treg transcription factor FoxP3 was the highest in inactive RA and the lowest in active RA, while the Th17 transcription factor RORc showed a reverse trend. An inverse correlation was observed between the FoxP3/RORc ratio and Disease Activity Score 28. Intervention of MaR1 in the CIA model reduced joint inflammation and damage, and improved the imbalanced Treg/Th17 ratio. MaR1 increased Treg cells proportion while reduced Th17 cells proportion under specific differentiation conditions. Furthermore, miR-21 was verified as MaR1 downstream microRNA, which was upregulated by MaR1, modulating the Treg/Th17 balance and thus ameliorating the RA progression. CONCLUSIONS: MaR1 is a therapeutic target for RA, likely operating through effects on the imbalanced Treg/Th17 ratio found in the disease.

Molecular detection and genetic characterizations of Cryptosporidium spp. in farmed foxes, minks, and raccoon dogs in northeastern China.

Cryptosporidium spp. are common intestinal protozoa causing diarrhea in humans and a variety of animal species. With the recent development of fur industry, a large number of fur animals are farmed worldwide, especially in China. The existence of identical Cryptosporidium species/genotypes in humans and fur animals suggests zoonotic potential. In order to assess the presence of zoonotic Cryptosporidium species and/or genotypes in farmed fur animals, 367 fecal specimens were collected from 213 foxes, 114 minks and 40 raccoon dogs farmed in Heilongjiang, Jilin, and Liaoning provinces, northeastern China, during the period from June 2014 to October 2016. By PCR and sequencing of the partial small subunit (SSU) rRNA gene of Cryptosporidium, 20 of 367 (5.4%) animal samples were found to be infected, corresponding to 12 of 213 fox samples (5.6%) and 8 of 114 mink samples (7.0%) screened. Three Cryptosporidium species/genotypes were identified: C. canis (n = 17), C. meleagridis (n = 1) and Cryptosporidium mink genotype (n = 2). Two host-adapted C. canis types (C. canis dog genotype and C. canis fox genotype) were found. By PCR and sequencing of the partial 60 kDa glycoprotein (gp60) encoding gene, one mink genotype isolate was successfully subtyped as XcA5G1R1. The three Cryptosporidium species/genotypes identified in this study have been previously reported in humans suggesting that fur animals infected with Cryptosporidium spp. may pose a risk of zoonotic transmission of cryptosporidiosis, especially for the people working in fur animal farming and processing industry.

Acclimation of 2-chlorophenol Biodegrading Activated Sludge and Microbial Community Analysis.

Taking glucose as co-substrate, the activated sludge which could effectively biodegrade 2-chlorophenol (2-CP) of 40 mg/L　was successfully domesticated after acclimation for 49 days in sequencing batch reactors. High-throughput sequencing (HTS) analysis revealed that the community richness initially increased for 5 days and then decreased after another 20 days with the increase of 2-CP. The original sludge obtained from water resource recovery facility had the highest diversity. At the beginning of acclimation, the community diversity decreased. With the acclimation going on, both richness and diversity of community increased, but decreased significantly when the concentration of 2-CP was increased to 40 mg/L. Saccharibacteria_norank, Bacillus, Saprospiraceae_uncultured and Lactococcus were the dominant bacteria detected in this study. Bacillus and Pseudomonas were the main chlorophenol-degrading bacteria. WCHB1-60_norank, Tetrasphaera, Comamonadaceae_unclassified and Haliangium had lower tolerance to 2-CP. Higher bacterial tolerance to CPs does not mean higher degrading capability. The degradation of CPs was not positively correlated with the abundance of known 2-CP degrading bacteria detected in this study.