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The matching of poly(ethylene oxide) (PEO)-based electrolytes with ultrahigh-nickel cathode materials is crucial for designing new-generation high-energy-density solid-state lithium metal batteries (SLMBs), but it is limited by serious interfacial side reactions between PEO and ultrahigh-nickel materials. Here, a high-concentration electrolyte (HCE) interface with a customized Li + solvation sheath is constructed between the cathode and the electrolyte. It induces the formation of an anion-regulated robust cathode/electrolyte interface (CEI), reduces the unstable free-state solvent, and finally achieves the compatibility of PEO-based electrolytes with ultrahigh-nickel cathode materials. Meanwhile, the corrosion of the Al current collector caused by lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) ions is prevented by lithium difluoro(oxalato)borate (LiDFOB) ions. The synergistic effect of the double lithium salt is achieved by a well-tailored ratio of TFSI - and DFOB - in the first solvation sheath of Li + . Compared with reported PEO-based SLMBs matched with ultrahigh-nickel (Ni ≥ 90%) cathodes, the SLMB in this work delivers a high discharge specific capacity of 216.4 mAh g -1 (0.1C) even at room temperature. This work points out a direction to optimize the cathode/electrolyte interface.

Benefiting from high energy density of ultrahigh-nickel cathode materials and good safety of PEO-based electrolytes, PEO-based ultrahigh-nickel solid-state lithium batteries (SLMBs) are considered to be new-generation energy storage devices. However, the incompatibility of ultrahigh-nickel cathode materials and PEO-based electrolytes is the main challenge due to serious interfacial side reactions. Therefore, the modification of the cathode/electrolyte interface is crucial. Herein, the residual lithium on the surface of LiNi 0.9 Co 0.06 Mn 0.04 O 2 is utilized to construct an interfacial coating layer by reacting with H 3 BO 3 . The in situ formed x Li 2 O-B 2 O 3 coating layer (LBO1-NCM) with high ionic conductivity can be regulated with different crystal structures during the sintering process. Besides, an all-solid-state three-electrode cell is fabricated, which verifies that the x Li 2 O-B 2 O 3 coating can effectively stabilize the interface. Astonishingly, uneven Li anode deposition is observed in SLMBs, which is caused by the breakage of PEO molecular chains due to the strong oxidation of the cathode, while this crosstalk is also suppressed by the x Li 2 O-B 2 O 3 coating layer. Consequently, Li|PEO|LBO1-NCM achieves a substantially improved electrochemical performance, exhibiting 90.5% of capacity retention after 100 cycles for the coin cell and 80.3% of capacity retention after 200 cycles for the pouch cell. Apparently, the targeted modification of interfaces should be paid as much attention as electrolyte optimization in SLMBs., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Tuberculosis is a chronic infectious disease, caused by Mycobacterium tuberculosis , that seriously endangers human health. Skeletal tuberculosis is the most common type of extrapulmonary tuberculosis and tuberculous arthritis is the second most common type of skeletal tuberculosis. We report a case series of patients with tuberculous arthritis, two of whom had no joint disease in the past and presented as monoarthritis. The final patient had a history of rheumatoid arthritis, with polyarthritis that was aggravated during treatment with glucocorticoids and immunosuppressive drugs. This series of cases can contribute to early diagnosis and treatment with appropriate infection control measures., (© 2024 The Authors.)

Background: The epidermic microbiota plays crucial roles in the pathogenesis of atopic dermatitis (AD), a common inflammatory skin disease. Melatonin (MLT) has been shown to ameliorate skin damage in AD patients, yet the underlying mechanism is unclear., Methods: Using 2,4-dinitrofluorobenzene (DNFB) to induce an AD model, MLT intervention was applied for 14 days to observe its pharmaceutical effect. Skin lesions were observed using HE staining, toluidine blue staining and electron microscopy. Dermal proinflammatory factor (IL-4 and IL-13) and intestinal barrier indices (ZO1 and Occludin) were assessed by immunohistochemistry and RT-qPCR, respectively. The dysbiotic microbiota was analyzed using 16S rRNA sequencing., Results: MLT significantly improved skin lesion size; inflammatory status (mast cells, IgE, IL-4, and IL-13); and the imbalance of the epidermal microbiota in AD mice. Notably, Staphylococcus aureus is the key bacterium associated with dysbiosis of the epidermal microbiota and may be involved in the fine modulation of mast cells, IL-4, IL-13 and IgE. Correlation analysis between AD and the gut revealed that intestinal dysbiosis occurred earlier than that of the pathological structure in the gut., Conclusion: Melatonin reverses DNFB-induced skin damage and epidermal dysbiosis, especially in S. aureus., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Tribe Zyginelline leafhoppers can transmit plant viruses and are important pests that affect agriculture, forestry, and animal husbandry, causing serious economic losses. The potential distribution patterns of Zyginellini will change under climate change. Therefore, the best-performing random forest and maximum entropy models among 12 commonly used ecological niche models, alongside an ensemble model, were selected to predict the changes in habitat suitability distribution of Zyginellini under current and future climate scenarios [represented by two shared socio-economic pathways (SSPs), namely SSP126 and SSP585, for three periods (2050s, 2070s, and 2090s)] in China and the Indo-China Peninsula for the first time., Results: The results revealed that the distribution of Zyginellini was mainly dominated by minimum temperature of coldest month. Under current and future climate scenarios, Zyginellini was mostly distributed southeast of the 400 mm equivalent precipitation line in China, and Vietnam. Under the future SSP126 scenario, the alert areas will mainly be concentrated in Hunan, Jiangxi, Zhejiang, Anhui, and Hebei in China, alongside Myanmar and Thailand in the Indo-China Peninsula. Meanwhile, in the SSP585 scenario, the alert areas in China will increase, whereas there will be little change in the Indo-China Peninsula. Interestingly, from the current to the future, the cores of Zyginelline distribution occurred around rivers and mountains, and shifted from Guizhou along the Yuanjiang River system to higher latitudes in Hunan., Conclusion: Zyginellini prefers higher latitude river-mountain systems under climate change. Our results will contribute to effective pest control strategies and biogeographical research for Zyginellini alongside other Cicadellidae insects. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Spaceflight is physically demanding and can negatively affect astronauts' health. It has been shown that the human gut microbiota and cardiac function are affected by spaceflight and simulated spaceflight. This study investigated the effects of the gut microbiota on simulated spaceflight-induced cardiac remodeling using 10° of head-down bed rest (HDBR) in rhesus macaques and 30° of hindlimb unloading (HU) in mice. The gut microbiota, fecal metabolites, and cardiac remodeling were markedly affected by HDBR in macaques and HU in mice, cardiac remodeling in control mice was affected by the gut microbiota of HU mice and that of HU mice was protected by the gut microbiota of control mice, and there was a correlation between cardiac remodeling and the gut microbial-derived metabolite trimethylamine N-oxide. These findings suggest that spaceflight can affect cardiac remodeling by modulating the gut microbiota and fecal metabolites., Competing Interests: The authors declare that they have no conflict of interest with the contents of this article., (© 2023 The Authors.)

Background: Online game addiction has become a prominent public concern, particularly among emerging adults, warranting in-depth investigation. Despite prior cross-sectional research indicating a negative correlation between gratitude and online gaming addiction, a dearth of longitudinal research exists in this area. Furthermore, the underlying mechanisms that explain the link between gratitude and online gaming addiction remain poorly understood, highlighting a critical research gap in the field., Methods: To bridge this gap, our study adopted a three-wave longitudinal design and constructed a multiple mediation model. Over the course of one year, data was collected from a sample of Chinese undergraduates, with 319 students participating at Time 1, 305 at Time 2, and 292 at Time 3. Participants were administered online self-report surveys, enabling the acquisition of valuable data regarding their levels of gratitude, online game addiction, self-control, and loneliness., Results: The findings revealed a negative correlation between gratitude measured at Time 1 and online game addiction assessed at Time 3. Further analysis demonstrated that both self-control and loneliness played multiple mediating roles at Time 2 in the link between gratitude and online game addiction., Conclusion: These research findings shed light on the underlying mechanisms between gratitude and online game addiction, which provide implications for developing interventions (e.g., interventions based on gratitude) for reducing young adults' online game addiction., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: With the popularity of mobile socialization, people have become more closely connected with their phones. While people enjoy the convenience that phones bring (e.g., accessing information and socializing), they also feel anxious about missing out on certain information. Previous researches have shown that fear of missing out (FoMO) can trigger depressive symptoms, however, the underlying psychological mechanisms are not yet clear. In addition, limited research has explored this issue in the context of mobile social media., Methods: To address this research gap, we surveyed 486 Chinese college students (278 males and 208 females, mean age = 19.95 years, SD = 1.14) and all participants completed a self-report questionnaire including mobile social media-related FoMO scale, phubbing scale, social exclusion scale, and the patient health questionnaire-9. The data were analyzed by SPSS24.0 and the Process macro and developed a mediating and moderating model incorporating phubbing and social exclusion., Results: The results showed that (1) mobile social media-related FoMO (MSM-related FoMO) can significantly and positively predict depressive symptoms among college students; (2) phubbing partially mediates the relationship between MSM-related FoMO and depressive symptoms; (3) the direct predictive effect of MSM-related FoMO on depressive symptoms is moderated by social exclusion., Conclusion: These findings are not only valuable for understanding the underlying mechanisms linking MSM-related FoMO and depressive symptoms, but also contribute to the development of psychological intervention programs (e.g., interventions based on social exclusion or phubbing) aiming at reducing college students' depressive symptoms., (© 2023. The Author(s).)

Spaceflight is rigorous and dangerous environment which can negatively affect astronauts' health and the entire mission. The 60 days of 6° head-down bed rest (HDBR) experiment provided us with an opportunity to trace the change of gut microbiota under simulated microgravity. The gut microbiota of volunteers was analyzed and characterized by 16S rRNA gene sequencing and metagenomic sequencing. Our results showed that the composition and function of the volunteers' gut microbiota were markedly was affected by 60 days of 6° HDBR. We further confirmed the species and diversity fluctuations. Resistance and virulence genes in the gut microbiota were also affected by 60 days of 6° HDBR, but the species attributions remained stable. The human gut microbiota affected by 60 days of 6° HDBR which was partially consistent with the effect of spaceflight, this implied that HDBR was a simulation of how spaceflight affects the human gut microbiota., Competing Interests: The authors declare that they have no conflict of interest with the contents of this article., (© 2023 The Author(s).)

Background: Family resilience plays a crucial role in protecting the mental health and family stability of infertile patients. However, information associated with infertile families resilience is scarce. The double ABC-X model provides a roadmap for this, helps organize knowledge, and lays the foundation for knowledge development., Aims: To describe the current situation of family resilience of infertile women, and to test the predictive theoretical model of family resilience based on infertility stigma, individual resilience, coping style, and posttraumatic growth., Design: A cross-sectional study., Methods: A convenience sample of 372 infertile women undergoing in vitro fertilization were recruited between April and August 2020. The Chinese-Family Resilience Assessment Scale, Infertility Stigma Scale, Simplified Coping Style Questionnaire, Chinese version of Connor-Davidson Resilience Scale, and Chinese version of Post Traumatic Growth Inventory were used to measure family resilience, infertility stigma, individual resilience, coping style, and posttraumatic growth. Structural equation models were used to analyze the relationship among these variables., Results: The results showed that family resilience was related to infertility stigma, positive coping, and individual resilience. Moreover, the path analysis indicated that positive coping and individual resilience mediated the effects of infertility stigma on family resilience., Conclusions: A high level of stigma among infertile women should be identified. Interventions for targeting positive coping and individual resilience might ultimately increase their family resilience., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

Objectives: To explore the value of plasmablasts in predicting disease relapse in IgG4-related diseases (IgG4-RD)., Methods: Treatment-naïve IgG4-RD patients treated with glucocorticoid (GC) monotherapy or leflunomide (LEF) and GC combination therapy diagnosed at the Chinese PLA General Hospital during February 2017 and January 2018 were included in this study. The absolute plasmablast count was measured by using the absolute count tubes with flow cytometry. Patients were categorized into high and low plasmablast level groups by defining the median number of plasmablasts as the cut-off value. The characteristics of the clinical manifestations between the two groups were compared. In addition, the correlation of plasmablast count with other indicators and its clinical value in predicting disease relapse were evaluated., Results: Data of 37 treatment-naïve IgG4-RD patients were analyzed. The median (IQR) absolute count of plasmablasts was 4.0 (2.8-7.5)/μL, which was correlated with the lymphocyte percentage, serum IgG, IgG4, and IgG4/IgG. The baseline absolute count of plasmablasts was an independent risk factor for disease relapse in IgG4-RD patients (HR, 1.199; 95% CI, 1.030-1.396, P = 0.019), and the application of LEF was an independent protective factor (HR, 0.283; 95% CI, 0.106-0.759, p = 0.012)., Conclusions: The present study preliminarily indicated that baseline absolute plasmablast count may independently predict disease relapse in patients with IgG4-RD treated with GC monotherapy or LEF and GC combination therapy. More efforts are still needed to be performed in the future. Key Points • The absolute count of plasmablasts is correlated with the lymphocyte percentage, serum IgG, IgG4 and IgG4/IgG. • The baseline absolute plasmablast count may predict disease relapse in patients with IgG4-RD treated with GC monotherapy or LEF and GC combination therapy. • The application of LEF is an independent protective factor for disease relapse in IgG4-RD., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Purpose: Infertility has adverse effects on the quality of life (QoL) of infertile couples. Previous studies found important associations between sexual function, self-esteem and QoL, but mainly focused on one individual's approach rather than both partners. This study adopted a dyadic approach to evaluate the relationship between sexual function and QoL in couples with infertility through mediation and improving self-esteem., Patients and Methods: Between October 2020 and January 2021, 428 couples with infertility (n=856) undergoing in-vitro fertilization (IVF) at a tertiary hospital in Hefei, China, were registered for the current descriptive cross-sectional research. The dyads' sociodemographic and clinical features, as well as their sexual function, self-esteem, and QoL were evaluated. The Fertility quality of life scale (FertiQoL), Rosenberg Self-Esteem Scale (RSES), Female Sexual Function Index (FSFI), and International Index of Erectile Function-15 (IIEF-15) were used to evaluate the participants. The Actor-Partner Interdependence Mediation Model (APIMeM) was utilized to examine data from the dyadic relationships., Results: According to the APIMeM analysis, sexual function of individuals with infertility was directly and indirectly connected with their QoL, mediated through their self-esteem. The women's sexual function was found to be positively associated with their partner's QoL, with the women's self-esteem acting as a complete mediator. The men's sexual function was found to be positively associated with partner's QoL, with the men's self-esteem acting as a complete mediator., Conclusion: The findings suggest that boosting participants' self-esteem can help them and their partners have a better QoL. Also, therapies aimed at improving and sustaining self-esteem of couples with infertility could help mitigate the negative influence of low sexual function on their QoL., Competing Interests: Jingfang Hong and Yunxia Cao should be considered joint senior author. The authors declare no conflict of interest., (© 2022 Wang et al.)

β- N -acetylhexosaminidases (EC3.2.1.52), which belong to the glycosyl hydrolase family GH20, are important enzymes for oligosaccharides modification. Numerous microbial β- N -acetylhexosaminidases have been investigated for applications in biology, biomedicine and biotechnology. Akkermansia muciniphila is an anaerobic intestinal commensal bacterium which possesses specific β- N -acetylhexosaminidases for gut mucosal layer colonization and mucin degradation. In this study, we assessed the in vitro mucin glycan cleavage activity of the A. muciniphila β- N -acetylhexosaminidase Am2136 and demonstrated its ability that hydrolyzing the β-linkages joining N -acetylglucosamine to a wide variety of aglycone residues, which indicated that Am2136 may be a generalist β- N -acetylhexosaminidase. Structural and enzyme activity assay experiments allowed us to probe the essential function of the inter-domain interactions in β23-β33. Importantly, we revealed that the hydrolysis activity of Am2136 was enhanced by nucleotides. We further speculated that this activation mechanism might be associated with the conformational motions between domain III and IV. To our knowledge, this is the first report of nucleotide effector regulated β- N -acetylhexosaminidase, to reveal its novel biological functions. These findings contribute to understanding the distinct properties within the GH20 family and lay a certain foundation to develop controllable glycan hydrolyzing catalysts. Abbreviations : OD600 - optical cell densities at 600 nm; LB - Luria-Bertani; IPTG - isopropyl β-D-1-thiogalactopyranoside; PMSF - phenylmethanesulfonyl fluoride; rmsd - root mean square deviation; GlcNAc - N-acetyl-β-D-glucosamine; GalNAc - N-acetyl-β-D-galactosamine; Gal - galactose.

This study aimed to develop a method, followed by gas chromatography-mass spectrometry, for detecting 37 pesticides in Chrysanthemum indicum ( C. indicum ) and investigating the decrease in the matrix-induced enhancement effect. The influence of QuEChERS extraction and matrix solid-phase dispersion (MSPD) on the recovery and matrix effect (ME) was compared. extraction and matrix solid-phase dispersion (MSPD) on the recovery and matrix effect (ME) was compared to decrease the ME. The cleanup sorbents, volume and type of solvent, and treatment time were optimized. The accuracy (as recovery), precision (as relative standard deviation, RSD), linearity, limit of quantitation, and limit of detection were determined. The recoveries at the three levels using mixed standard solution ranged between 76% and 120% with RSD ≤15%, and 76% and 120% with RSD ≤11% for MSPD and QuEChERS extraction, respectively. The results suggested that the ME for 21 pesticides was in the range of 80%-120% after MSPD and 15% after QuEChERS extraction. QuEChERS extraction was simpler and faster than MSPD. This methodology was applied in the analysis of 27 C. indicum samples; phorate was most frequently detected (63.0% of the sample)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Xiao-Ying Lu et al.)

Akkermansia muciniphila, an anaerobic Gram-negative bacterium, is a major intestinal commensal bacterium that can modulate the host immune response. It colonizes the mucosal layer and produces nutrients for the gut mucosa and other commensal bacteria. It is believed that mucin desulfation is the rate-limiting step in the mucin-degradation process, and bacterial sulfatases that carry out mucin desulfation have been well studied. However, little is known about the structural characteristics of A. muciniphila sulfatases. Here, the crystal structure of the premature form of the A. muciniphila sulfatase AmAS was determined. Structural analysis combined with docking experiments defined the critical active-site residues that are responsible for catalysis. The loop regions I-V were proposed to be essential for substrate binding. Structure-based sequence alignment and structural superposition allow further elucidation of how different subclasses of formylglycine-dependent sulfatases (FGly sulfatases) adopt the same catalytic mechanism but exhibit diverse substrate specificities. These results advance the understanding of the substrate-recognition mechanisms of A. muciniphila FGly-type sulfatases. Structural variations around the active sites account for the different substrate-binding properties. These results will enhance the understanding of the roles of bacterial sulfatases in the metabolism of glycans and host-microbe interactions in the human gut environment.

Two new species of the leafhopper tribe Erythroneurini from Guizhou province, China, Arboridia (Arboridia) huajiangensis sp. nov. and Arboridia (Arborifera) changlingensis sp. nov. are described and illustrated. The ovipositor of A. huajiangensis sp. nov. is photographed and described. A key distinguishing all known species of the genus in China is provided.

The vascular endothelium, which plays an essential role in maintaining the normal shape and function of blood vessels, is a natural barrier between the circulating blood and the vascular wall tissue. The endothelial damage can cause vascular lesions, such as atherosclerosis and restenosis. After the vascular intima injury, the body starts the endothelial repair (re-endothelialization) to inhibit the neointimal hyperplasia. Endothelial progenitor cell is the precursor of endothelial cells and plays an important role in the vascular re-endothelialization. However, re-endothelialization is inevitably affected in vivo and in vitro by factors, which can be divided into two types, namely, promotion and inhibition, and act on different links of the vascular re-endothelialization. This article reviews these factors and related mechanisms.

Objectives: To evaluate the efficacy and safety of leflunomide (LEF) and glucocorticoids (GCs) combination therapy compared with GCs monotherapy in preventing relapse of IgG4-related disease (IgG4-RD)., Methods: A 12-month, randomized, open-label, controlled trial was conducted at a large academic medical center (ClinicalTrials.gov: NCT02703194). Enrolled patients with active IgG4-RD were randomly allocated to the GCs + LEF (20 mg/day) combination therapy or GCs monotherapy group. All patients received GCs with a predefined taper regimen starting from a dosage of 0.5-0.8 mg/kg/d. The primary outcome was the time to relapse. The secondary outcomes included complete response, remission, GCs dosage, and serum IgG4 level., Results: Sixty-six patients with active IgG4-RD were enrolled (33 patients in each group). The demographic and disease characteristics showed no statistically significant differences between groups. Additionally, the initial GCs dosages were similar (50.00 vs. 50.00 mg/day, P = 0.295). Disease relapses occurred in 6 (18.2%) and 14 (42.4%) patients in the combination therapy group and GCs monotherapy group, respectively (P = 0.032). The combination therapy was significantly superior to GCs monotherapy regarding the primary outcome, the time to relapse (HR, 0.35; 95% confidence interval [CI], 0.13-0.90; P = 0.023), as well as the secondary outcome, the time to complete response (HR, 1.75; 95% CI, 1.01-3.02; P = 0.034). A longer duration of remission was observed in the combination therapy group (7.00 vs. 3.00 months, P = 0.002) and less cumulative dosage of GCs was used (5103.13 vs. 5637.50 mg, P = 0.031). Additionally, a higher proportion of patients in the combination therapy group (54.5%) were able to reach a daily GCs dose of ≤5 mg/day compared with the GCs monotherapy group (18.2%) (P = 0.006). The incidences of adverse events were similar in the 2 groups (P = 0.325)., Conclusion: LEF in combination with GCs therapy is well-tolerated and significantly superior to GCs monotherapy in preventing the relapse of IgG4-RD. LEF can be used as a steroid-sparing agent in the management of IgG4-RD., Competing Interests: Declaration of competing interest The authors have declared no conflicts of interest in this work., (Copyright © 2020. Published by Elsevier Inc.)

Interaction between humans and the gut microbiota is important for human physiology. Here, the gut microbiota was analyzed via metagenomic sequencing, and the fluctuations in the gut microbiota under the conditions of spaceflight were characterized. The composition and function of the gut microbiota were substantially affected by spaceflight; however, individual specificity was uncompromised. We further confirmed the species fluctuations and functional genes from both missions. Resistance and virulence genes in the gut microbiota were affected by spaceflight, but the species attributions remained stable. Spaceflight markedly affected the composition and function of the human gut microbiota, implying that the human gut microbiota is sensitive to spaceflight.

Eosinophilic fasciitis (EF) is a rare connective tissue disease characterized by increased peripheral blood eosinophils and diffuse fasciitis, generalized morphea (GM) is a subtype of localized scleroderma, and IgA nephropathy is a chronic glomerulonephritis caused by abnormal deposition of IgA in the mesangial area of the glomeruli. We describe a 49-year-old male patient with hard skin, cutaneous hyperpigmentation, and proteinuria. The patient had suffered from a long disease course of hard skin, while urine protein was newly detected. Finally, the clinical presentation and physical examination, limb MRI, skin biopsy, and renal biopsy confirmed the diagnosis of eosinophilic fasciitis associated with generalized morphea and IgA nephropathy. This case is the first report of EF associated with GM and IgA nephropathy., (© 2020 Wiley Periodicals LLC.)

Objective: Bone loss is common in AS, and miR-214 plays an important role in regulating bone formation. The aim of this study was to investigate the effect of miR-214, the production of which is stimulated by IL-17A, on bone loss in AS., Methods: Peripheral blood was obtained from 32 patients with AS and 24 healthy controls. Levels of IL-17A, soluble RANK ligand (RANKL) and osteoprotegerin in serum were evaluated by ELISA, and the relative level of miR-214 in serum was detected by real-time quantitative PCR. In addition, we assessed the relationship between levels of miR-214, IL-17A and bone loss in primary murine osteoblasts and mouse bone marrow cells., Results: The expression of RANKL and miR-214 in osteoblasts was increased following stimulation by IL-17A, and osteoblasts stimulated by IL-17A promoted the expression of miR-214 in osteoclasts and the activity of osteoclasts. We showed that osteoblast-derived miR-214 could be transferred to osteoclasts and could then regulate their activity. The levels of IL-17A and miR-214 were much higher in the serum of patients with AS than in that of healthy controls, and the relative level of miR-214 was positively correlated with the level of IL-17A in the serum and synovial fluid of the patients with AS, not healthy controls. The level of miR-214 in the serum of AS patients has potential diagnostic value., Conclusion: The production of miR-214 in osteoblasts is stimulated by IL-17A. It is an important inhibitor of bone formation in AS, and the serum level of miR-214 might be of potential diagnostic value for AS., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Rationale : The existence of primary and acquired drug resistance is the main obstacle for the effect of multi-kinase inhibitor sorafenib and regorafenib in advanced hepatocellular carcinoma (HCC). However, plenty of patients did not significantly benefit from sorafenib treatment and little is known about the mechanism of drug resistance. Methods : Laser capture microdissection was used to acquire matched normal liver and tumor tissues on formalin-fixed paraffin-embedded specimens collected before sorafenib therapy from the first surgery of 119 HCC patients. Ultra-deep sequencing (~1000×) targeting whole exons of 440 genes in microdissected specimens and siRNA screen in 7 cell lines were performed to find mutations associated with differential responses to sorafenib. Patient-derived xenograft models were employed to determine the role of TP53 in response to sorafenib. Lentiviruses harboring wild-type and c.G52C-mutant OCT4 were applied to explore the function of OCT4 in resistance to sorafenib. ChIP-PCR assay for analysis of OCT4 transcriptional activity was performed to explore the affinity with the KITLG promoter. Statistical analyses were used to associate levels of p53 and OCT4 with tumor features and patient outcomes. Results : Total 1,050 somatic mutations and 26 significant driver genes were identified. SiRNA screening in 7 HCC cell lines was further performed to identify mutations associated with differential responses to sorafenib. A recurrent nonsynonymous mutation c.G52C in OCT4 ( OCT4 mut ) was strongly associated with good response to sorafenib, whereas the stop-gain mutation in TP53 showed the opposite outcome both in vitro and in vivo. OCT4 wt -induced stem cell factor (encoded by KITLG gene, SCF) expression and cross-activation of c-KIT/FLT3-BRAF signals were identified indispensably for sorafenib resistance, which could be reversed by the combination of c-KIT tyrosine kinase inhibitors or neutralizing antibody against SCF. Mechanistically, an OCT4 binding site in upstream of KITLG promoter was identified with a higher affinity to wildtype of OCT4 rather than G52C-mutant form, which is indispensable for OCT4-induced expression of KITLG and sorafenib resistance. Conclusion : Our study reported a novel somatic mutation in OCT4 (c.G52C) responsible for the sorafenib effect, and also shed new light on the treatment of HCC through the combination of specific tyrosine kinase inhibitors according to individual genetic patterns., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Transarterial chemoembolization (TACE) and percutaneous microwave coagulation therapy (PMCT) are commonly used to treat intrahepatic recurrent liver cancers. However, there is no information regarding their effectiveness in patients with recurrent intrahepatic cholangiocarcinoma (ICC) after resection., Methods: A total of 275 patients with localized recurrent ICC who received either TACE (n = 183) or PMCT (n = 92) were studied. A propensity score matching analysis was performed to compare prognostic impact of TACE and PMCT. Prognostic factors for TACE and PMCT were identified respectively. Predictive nomograms for each TACE and PMCT were developed using the Cox independent prognostic factors and were validated in independent patient groups by receiver operating characteristic curves and area under curve values., Results: Both TACE and PMCT provided curativeness in partial patients (5-year overall survival: 21.4% and 6.1%, respectively), but TACE provided better survival benefit in both overall patients (hazard ratio [HR] = 0.71; 95% confidence interval [CI]: 0.50-0.97; P = 0.034) and propensity score matching analysis (HR = 0.69; 95% CI: 0.47-0.98; P = 0.041). Independent prognostic factors for TACE were tumor size >5 cm, poor differentiation, and major resection, whereas poor differentiation, hepatitis B virus infection, cholelithiasis, and lymph node metastasis were identified for PMCT. Both predictive nomograms for TACE and PMCT were validated to be effective with area under curve values of 0.77 and 0.70, respectively., Conclusions: TACE provided better survival benefits compared to PMCT. However, there was a disparity in prognostic factors, suggesting evaluation of the two nomograms may be supportive in modality selection. Further prospective validation studies are required for the results to be applied in clinical medicine., (Copyright © 2020 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

An oncogenic role, p21-activated kinase 5 (PAK5), has proven as a significant mediator for many cellular progression, which is expressed highly in human organs such as lung, liver, kidney, blood vessels endothelial cells and inflammatory cells. PAK5 was primitively detected in the cerebrum and accelerated the filopodia formation in neurocytes. It can reverse the effect of Rho and adjust its activity to mediate maintenance and development of nerve axon by binding with Cdc42-GTP. Moreover, PAK5 has been suggested to mediate protean, multitudinous and inscrutable functions in cancer. Currently, many researches indicated that PAK5 was dysregulated in ovarian cancer, cervical cancer, melanoma, osteosarcoma, renal carcinoma, breast cancer, gastric cancer and so on, which was involved in cell proliferation, apoptosis, migration and invasion. This review focuses the latest knowledge on the structure, expression, signalling pathway of PAK5, emphasizing its function in cancer., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Circular RNA (circRNA) possesses great pre-clinical diagnostic and therapeutic potentials in multiple cancers. It has been reported playing roles in multiple malignant behaviors including proliferation, migration, metastasis and chemoresistance. However, the underlying correlation between circRNAs and cancer stem cells (CSCs) has not been reported yet. Methods: circZKSCAN1 level was detected in HCC tissue microarrays to clarify its prognostic values. Gain and loss function experiments were applied to investigate the role of circZKSCAN1 in HCC stemness. Bioinformatic analysis was used to predict the possible downstream RNA binding protein and further RNA immunoprecipitation sequencing was carried out to identify the RBP-regulated genes. Results: The absence of circZKSCAN1 endowed several malignant properties including cancer stemness and tightly correlated with worse overall and recurrence-free survival rate in HCC. Bioinformatics analysis and RNA immunoprecipitation-sequencing (RIP-seq) results revealed that circZKSCAN1 exerted its inhibitive role by competitively binding FMRP, therefore, block the binding between FMRP and β-catenin-binding protein-cell cycle and apoptosis regulator 1 (CCAR1) mRNA, and subsequently restrain the transcriptional activity of Wnt signaling. In addition, RNA-splicing protein Quaking 5 was found downregulated in HCC tissues and responsible for the reduction of circZKSCAN1. Conclusion: Collectively, this study revealed the mechanisms underlying the regulatory role of circZKSCAN1 in HCC CSCs and identified the newly discovered Qki5-circZKSCAN1-FMRP-CCAR1-Wnt signaling axis as a potentially important therapeutic target for HCC treatment., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Introduction: To investigate the effect of dose maintenance, reduction, or discontinuation of the etanercept biosimilar Yisaipu (YSP) on early axial spondyloarthritis (axSpA) patients in remission with YSP 50 mg once weekly (QW)., Material and Methods: Patients were enrolled in three groups: full dose (YSP50), half dose (YSP25), and discontinuation (YSP0). Patients were assessed by the same rheumatologist every 8 weeks for 48 weeks. The primary endpoint was the proportion of non-failure patients in each group. If a flare occurred during the study period, the patient resumed YSP 50 mg QW or was switched to another tumor necrosis factor inhibitor., Results: A total of 144 patients were included and each group included 48 patients. The proportion of non-failure patients was significantly greater in the YSP50 group than in the YSP0 group at 48 weeks (91.7% vs. 72.9%, p = 0.032). The difference in the other two comparisons was not statistically significant (YSP50 vs. YSP25 group, p = 0.522; YSP25 vs. YSP0 group, p = 0.132). The median time to flare did not differ significantly between the three groups ( p > 0.05). Most patients who flared regained remission rapidly after resuming YSP 50 mg QW or starting adalimumab 40 mg every other week., Conclusions: For patients with early axSpA in remission on YSP for more than 12 weeks, continuation of YSP at full dose was superior to discontinuation of YSP, but not superior to halving the dose., Competing Interests: The authors declare no conflict of interest.

Background: FOXD3 is aberrantly regulated in several tumors, but its underlying mechanisms in ovarian cancer (OC) remains largely unknown. The present study aimed to explore the role and associated mechanisms of FOXD3 in OC., Methods: Microarray data from GEO was used to analyze differential CpG sites and differentially methylated regions (DMR) in tumor tissues and Illumina 450 genome-wide methylation data was employed. The FOXD3 expression level was determined through qRT-PCR and western blot analysis. Wound healing test, colony formation and flow cytometry assay were utilized to analyze cell migration, proliferation abilities, cell cycle and cell apoptosis, respectively. Finally, the effect of FOXD3 on tumor growth was investigated through in vivo xenograft experiments., Results: GEO data analysis showed that FOXD3 was hypermethylated in OC tissues. Also, qRT-PCR revealed that FOXD3 was low expressed and methylation-specific PCR (MSP) confirmed that the methylation level of FOXD3 was hypermethylated. Combined treatment of 5-aza-2'-deoxycytidine (5-Aza-dC) could synergistically restored FOXD3 expression. Finally, in vitro and in vivo experiments showed that demethylated FOXD3 decreased cell proliferation and migration abilities, and increased the cell apoptosis. In vivo experiment detected that demethylated FOXD3 restrained tumor growth., Conclusions: FOXD3 could act as a tumor suppressor to inhibit cell proliferation, migration and promote cell apoptosis in OC cells.

Hypoxia-induced apoptosis is an inevitable problem in cyanotic congenital heart disease. In the present study, we investigated effects of melatonin on hypoxic cardiomyocytes in vitro and in vivo, and explored its underlying mechanism. H9C2 cells were subjected to hypoxia for 48 hours. Mice were subjected to hypoxia treatment (10% O 2 ) for 4 weeks. Cell viability was detected by the cell counting kit-8 assay. Cellular apoptosis was assessed by Annexin V/7 AAD assay. Western blotting was employed to determine the expression of Bcl-2, Bax, cleaved caspase 3, phosphorylation of PI3K, and AKT. Melatonin increased cell viability and alleviated apoptosis in hypoxic H9C2 cells and cardiomyocytes of hypoxia-treated mice. Melatonin pretreatment increased Bcl-2 and decreased cleaved caspase 3 and Bax levels. Moreover, melatonin activated the PI3K/Akt pathway. The protective effects of melatonin were abolished by a PI3K/Akt-inhibitor, LY294002. Our results demonstrated that melatonin confers cardioprotection by inhibiting apoptosis through the activation of PI3K/Akt signaling pathway in hypoxic cardiomyocytes., Competing Interests: None., (IJCEP Copyright © 2018.)

DNA barcoding, based on a fragment of cytochrome c oxidase I (COI) mtDNA, is as an effective molecular tool for identification, discovery, and biodiversity assessment for most animals. However, multiple gene markers coupled with more sophisticated analytical approaches may be necessary to clarify species boundaries in cases of cryptic diversity or morphological plasticity. Using 339 moths collected from mountains surrounding Beijing, China, we tested a pipeline consisting of two steps: (1) rapid morphospecies sorting and screening of the investigated fauna with standard COI barcoding approaches; (2) additional analyses with multiple molecular markers for those specimens whose morphospecies and COI barcode grouping were incongruent. In step 1, 124 morphospecies were delimited into 116 barcode units, with 90% of the conflicts being associated with specimens identified to the genus Hypena. In step 2, 55 individuals representing all 12 Hypena morphospecies were analysed using COI, COII, 28S, EF-1a, Wgl sequences or their combinations with the BPP (Bayesian Phylogenetics and Phylogeography) multigene species delimitation method. The multigene analyses supported the delimitation of 5 species, consistent with the COI analysis. We conclude that a two-step barcoding analysis pipeline is able to rapidly characterize insect biodiversity and help to elucidate species boundaries for taxonomic complexes without jeopardizing overall project efficiency by substantially increasing analytical costs.

Background: As one kind of osteochondrodysplasia, progressive pseudorheumatoid dysplasia (PPD) is also known as spondyloepiphyseal dysplasia tarda with progressive arthropathy or arthropathy progressive pseudorheumatoid of childhood. PPD is a very rare disease, especially in China, and has an estimated prevalence of 1/1000000 due to lacking definite prevalence survey. It is an autosomal recessive disorder caused by gene mutation of Wntl inducible signaling pathway protein 3 (WISP3). Its basic pathological change is persistent degeneration and loss of articular cartilage in multiple joints. Its clinical appearances include bone enlargement, platyspondyly, irregular endplate, secondary osteoarthritis, extensive osteoporosis, joint rigidity and function loss. Clinical diagnosis of PPD is made based on clinical appearance and imaging examinations, whereas its definite diagnosis depends on gene sequencing. PPD has no severe effect on life span, but causes high disability rate and very poor prognosis. There are only case reports with limited information in China., Case Presentation: One female patient was diagnosed as PPD and secondary osteoarthritis. She had typical clinical appearance and imaging examinations, and received individualized therapeutic regimens. She had a gene mutation (c.72delT, p.T24TfsX4) of WISP3. This gene mutation has not been reported by previous literatures and included in Single Nucleotide Polymorphism Database., Conclusions: As the first time, this paper reported a patient with PPD caused by new-found gene mutation (c.72delT, p.T24TfsX4) of WISP3.

An organocatalytic [4 + 1] cyclization of o-QMs with MBH carbonates has been established using naphthylindole-derived phosphine (NIP) as an organocatalyst. By using this approach, a series of 2,3-dihydrobenzofuran derivatives have been synthesized in high yields and excellent diastereoselectivities (up to 99% yield, >95:5 dr). This reaction not only has established the first [4 + 1] cyclization of o-QMs with MBH carbonates but also represents the first application of naphthylindole-derived phosphines as organocatalysts in catalytic reactions. In addition, this reaction has also provided a useful method for constructing 2,3-dihydrobenzofuran scaffolds.

Background: The previous study showed that mycophenolic acid (MPA) synergizing with lipopolysaccharide (LPS) promoted interleukin (IL)-1β release, but the mechanism is unclear. This study aimed to investigate the mechanism of MPA synergizing with LPS to induce IL-1β release., Methods: Undiluted human blood cells, THP-1 human myeloid leukemia mononuclear cells (THP-1) cells, or monocytes were stimulated with LPS and treated with or without MPA, and the supernatant IL-1β was detected by enzyme-linked immunosorbent assay. The mRNA levels of IL-1β were detected by real-time quantitative polymerase chain reaction. The intracellular protein levels of nuclear factor kappa B (NF-κB) phospho-p65 (p-p65), precursor interleukin-1β (pro-IL-1β), NOD-like receptor pyrin domain containing-3 (NLRP3), and cysteine aspartic acid-specific protease-1 (caspase-1) p20 in THP-1 cell were measured by Western blot., Results: The MPA alone failed to induce IL-1β, whereas MPA synergized with LPS to increase IL-1β in a dose-dependent manner (685.00 ± 20.00 pg/ml in LPS + 5 μmol/L MPA group, P = 0.035; 742.00 ± 31.58 pg/ml in LPS + 25 μmol/L MPA group, P = 0.017; 1000.00 ± 65.59 pg/ml in LPS + 75 μmol/L MPA group, P = 0.024; versus 408.00 ± 35.50 pg/ml in LPS group). MPA alone has no effect on the IL-1β mRNA expression, LPS induced the expression of IL-1β mRNA 2761 fold, and LPS + MPA increased the IL-1β expression 3018 fold, which had the same effect with LPS group (P = 0.834). MPA did not affect the intracellular NF-κB p-p65 and pro-IL-1β protein levels but activated NLRP3 inflammasome. Ac-YVAD-cmk blocked the activation of caspase-1 and subsequently attenuated IL-1β secretion (181.00 ± 45.24 pg/ml in LPS + MPA + YVAD group vs. 588.00 ± 41.99 pg/ml in LPS + MPA group, P = 0.014)., Conclusions: Taken together, MPA synergized with LPS to induce IL-1β release via the activation of caspase-1, rather than the enhanced production of pro-IL-1β. These findings suggested that patients immunosuppressed with mycophenolate mofetil may have overly activated caspase-1 during infection, which might contribute to a more sensitive host defense response to invading germs., Competing Interests: There are no conflicts of interest

Effectors, a group of small proteins secreted by pathogens, play a critical role in the antagonistic interaction between plant hosts and pathogens through their dual functions in regulating host immune systems and pathogen infection capability. In this study, evolution in effector genes was investigated through population genetic analysis of Avr3a sequences generated from 96 Phytophthora infestans isolates collected from six locations representing a range of thermal variation and cropping systems in China. We found high genetic variation in the Avr3a gene resulting from diverse mechanisms extending beyond point mutations, frameshift, and defeated start and stop codons to intragenic recombination. A total of 51 nucleotide haplotypes encoding 38 amino acid isoforms were detected in the 96 full sequences with nucleotide diversity in the pathogen populations ranging from 0.007 to 0.023 (mean = 0.017). Although haplotype and nucleotide diversity were high, the effector gene was dominated by only three haplotypes. Evidence for a selective sweep was provided by (i) the population genetic differentiation ( G ST ) of haplotypes being lower than the population differentiation ( F ST ) of SSR marker loci; and (ii) negative values of Tajima's D and Fu's FS. Annual mean temperature in the collection sites was negatively correlated with the frequency of the virulent form (Avr3a EM ), indicating Avr3a may be regulated by temperature. These results suggest that elevated air temperature due to global warming may hamper the development of pathogenicity traits in P. infestans and further study under confined thermal regimes may be required to confirm the hypothesis.

It is urgent that the means to improve liver regeneration (LR) be found, while mitigating the concurrent risk of hepatocarcinogenesis (HCG). Nuclear receptor corepressor 1 (NCoR1) is a co-repressor of nuclear receptors, which regulates the expression level of metabolic genes; however, little is known about its potential contribution for LR and HCG. Here, we found that liver-specific NCoR1 knockout in mice (NCoR1 Δhep ) dramatically enhances LR after partial hepatectomy and, surprisingly, blocks the process of diethylnitrosamine (DEN)-induced HCG. Both RNA-sequencing and metabolic assay results revealed improved expression of Fasn and Acc2 in NCoR1 Δhep mice, suggesting the critical role of de novo fatty acid synthesis (FAS) in LR. Continual enhanced de novo FAS in NCoR1 Δhep mice resulted in overwhelmed adenosine triphosphate ATP and nicotinamide adenine dinucleotide phosphate (NADPH) consumption and increased mitochondrial reactive oxygen species production, which subsequently attenuated HCG through inducing apoptosis of hepatocytes at an early stage after DEN administration., Conclusion: NCoR1 functions as a negative modulator for hepatic de novo FAS and mitochondria energy adaptation, playing distinct roles in regeneration or carcinogenesis. (Hepatology 2018;67:1071-1087)., (© 2017 by the American Association for the Study of Liver Diseases.)

Objective: To discuss the utility of 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computerized tomography (PET/CT) in the diagnosis of idiopathic retroperitoneal fibrosis (iRPF)., Methods: IRPF patients diagnosed between September 2011 and June 2016 were included. Retroperitoneal malignancy patients were included as control. The morphological features and FDG uptake of retroperitoneal lesions were measured along with lymph node (LN) mapping., Results: Seventy-one iRPF patients were included. Fifteen lymphoma patients and 6 retroperitoneal metastatic malignancy patients were included as control. Significant differences in morphological features were observed between iRPF and lymphoma but not retroperitoneal metastatic carcinoma. Compared with malignancy, iRPF displayed a lower frequency of high-FDG-uptake retroperitoneal lesions (P = 0.017) and a lower mean maximum standardized uptake value (SUV max ) (P < 0.001). LNs located at axillary, retroperitoneal, supraclavicular, inguinal or peritoneal sites were more frequently observed in retroperitoneal malignancy, therefore, were defined as specific LNs. The area under the curve (AUC) for SUV max was 0.893 with a sensitivity of 85.7% and a specificity of 80.3%, when the cut-off value of the SUV max was 6.23. The AUC for the logistic regression model combining the lesions above renal arteries, the SUV max and the number of specific LNs was 0.987 with a sensitivity of 90.5% and a specificity of 98.6%. The risk stratification model analysis indicated that most of the retroperitoneal malignancy patients were at moderate or high level, while most of the iRPF patients were at low risk., Conclusions: Retroperitoneal malignancy can mimic iRPF morphologically. 18 F-FDG PET/CT can help to distinguish iRPF from retroperitoneal lymphoma and metastatic malignancy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Induction of cardiomyocyte proliferation, the most promising approach to reverse myocardial attrition, has been gaining importance as a therapy for cardiovascular disease. Hypoxia and macrophages were previously independently reported to promote cardiomyocyte proliferation in mice. However, whether hypoxia promotes cardiomyocyte proliferation in humans, and the association between hypoxia and macrophages in cardiomyocyte proliferation, have not to the best of our knowledge been previously investigated. The present study investigated the cardiomyocyte proliferation in 22 acyanotic and 29 cyanotic patients. Cardiomyocyte proliferation in a hypoxic mouse model (15% O2) was subsequently performed and the macrophage subsets were analyzed. A C‑C chemokine receptor type 2 (CCR2) inhibitor was used to increase the number of resident macrophages in order to investigate the effect of macrophages on cardiomyocyte proliferation. The results demonstrated that cardiomyocyte proliferation in the cyanotic infant group was significantly increased compared with the acyanotic infant group and the hypoxia‑treated C57BL/6J neonates confirmed the hypoxia‑induced cardiomyocyte proliferation. However, hypoxia did not induce the proliferation of isolated cardiomyocytes. Notably, hypoxia treatment increased the number of cardiac resident macrophages in neonate hearts. Furthermore, increasing the number of resident macrophages significantly enhanced cardiomyocyte proliferation. In conclusion, postnatal hypoxia promoted cardiomyocyte proliferation in humans and animals, and cardiac resident macrophages may be involved in this process. Therefore, this novel mechanism may provide a promising strategy for cardiovascular disease treatment.

Background: Although glucocorticoids are effective in IgG4-related disease (IgG4-RD), patients may relapse during or after glucocorticoid tapering. Immunosuppressive agents, including leflunomide (LEF), are regarded as steroid-sparing agents in other autoimmune disorders and need to be discussed in the management of IgG4-RD., Aim: To identify the efficacy and safety of combination therapy of LEF and glucocorticoids in IgG4-RD., Methods: We retrospectively summarised data of patients diagnosed with IgG4-RD between November 2012 and November 2015. Only patients treated with LEF plus glucocorticoids and had been followed up for more than three visits and 6 months were analysed with clinical symptoms, laboratory and imaging findings, treatment protocol, LEF-related adverse events and disease activity reflected by IgG4-RD Responder Index (IgG4-RD RI)., Results: A total of 18 patients, including 14 untreated patients and 4 relapsing patients, was included. The mean (SD) onset age was 54.0 (9.6) years. The mean (SD) follow-up period was 12.1 (7.4) months. All patients had active disease with mean (SD) IgG4-RD RI of 15.0 (5.6) at baseline and experienced improvements at 1 month. At the last follow up, the mean (SD) IgG4-RD Responder Index declined to 3.1 (1.7) in all patients and to 2.5 (1.2) in patients without relapse. The mean (SD) dose of GC declined to 6.9 (2.7) mg/day. A total of 12 (66.7%) and 11 (61.1%) patients were in remission at 6 months and the last follow up respectively. Three (16.7%) patients relapsed in clinical course. Two reversible adverse events were observed., Conclusion: The combination therapy of LEF and glucocoticoids is effective and safe in IgG4-RD., (© 2017 Royal Australasian College of Physicians.)

Potential biomarkers that can be used to determine prognosis and perform targeted therapies are urgently needed to treat patients with hepatocellular carcinoma (HCC). To meet this need, we performed a screen to identify functional genes associated with hepatocellular carcinogenesis and its progression at the transcriptome and proteome levels. We identified aldehyde dedydrogenase-2 (ALDH2) as a gene of interest for further study. ALDH2 levels were significantly lower at the mRNA and protein level in tumor tissues than in normal tissues, and they were even lower in tissues that exhibited increased migratory capacity. A study of clinical associations showed that ALDH2 is correlated with survival and multiple migration-associated clinicopathological traits, including the presence of metastasis and portal vein tumor thrombus. The result of overexpressing or knocking down ALDH2 showed that this gene inhibited migration and invasion both in vivo and in vitro. We also found that ALDH2 altered the redox status of cells by regulating acetaldehyde levels and that it further activated the AMP-activated protein kinase (AMPK) signaling pathway., Conclusion: Decreased levels of ALDH2 may indicate a poor prognosis in HCC patients, while forcing the expression of ALDH2 in HCC cells inhibited their aggressive behavior in vitro and in mice largely by modulating the activity of the ALDH2-acetaldehyde-redox-AMPK axis. Therefore, identifying ALDH2 expression levels in HCC might be a useful strategy for classifying HCC patients and for developing potential therapeutic strategies that specifically target metastatic HCC. (Hepatology 2017;65:1628-1644)., (© 2016 by the American Association for the Study of Liver Diseases.)

A novel alternating polymer, ProDOT-TPE, with aggregation-enhanced fluorescent emission and electrochromic properties based on thiophene and tetraphenylethene derivatives was designed, synthesized, and characterized. The polymer displays weak photoluminescence in tetrahydrofuran, but its corresponding film prepared by spray-coating exhibits yellow-green fluorescent light at 540 nm. The color of the polymer film could be switched from bright yellow to navy blue by applying a relatively low voltage. An electrochromic device (ECD) of the polymer was fabricated that differs from common ECDs because both its color and fluorescent state could be synchronously switched by an applied voltage, making the polymer a unique candidate for electrochemical fluorescence and electrochromic applications.

Gentianae Urnulae Herba, dried whole herb of Gentiana urnula,is a commonly used Tibetan medicine. However, only the character identification is used as quality control standard officially at present. As a part of project for the Chinese Pharmacopoeia (2015 edition), the quality standard of this species was established in this study. The tests of water content, total ash, acid-insoluble ash and ethanol-soluble extractives of the crude drugs were carried out following the methods recorded in appendix of Chinese Pharmacopeia (2010 edition, volume 1). The TLC identification method was established by using gentiournoside A as reference substance, and a mixture of ethyl acetate-methanol-water-formic acid(7:1. 5:1: 0. 2) as the developing solvent system on silica gel G TLC plate. The content of gentiournoside A was assayed by HPLC on an Agilent Zorbax SB-C18 (4.6 mm x 250 mm,5 μm) column, using acetonitrile-water (0.1% phosphoric acid) (26:74) as the mobile phase at a flow rate of 1.0 mL x min(-1). The column temperature is at 30 degrees C and the detection wavelength is at 240 nm. As a result, gentiournoside A and the other constituents were separated and presented the same fluorescence light comparing with the reference substance on TLC detected under the UV light(366 nm). The methodology validation for the assay of gentiournoside A showed that it was in a good linear correlation in the range of 0.009 95-0.398 g x L(-1) with the regression equation of Y = 1 467.1X +41.407(r = 0.999 9), and the average recovery was 98. 3% (RSD 2.2%). The mass fractions of gentiournoside A, water content, ethanol-soluble extractives of 15 batches samples were varied in the ranges of 0.175% -1.83%, 8.60% - 9.93% and 29.2% - 35.2%, respectively. Total ash and acid-insoluble ash were 10.2% - 17.2% and 5.26% - 10.8% detected from 10 batches samples. The recommended standards of quantitative indexes are that the mass fractions of gentiournoside A and extractives are not less than 0.80% and 26.0%, respectively; the water, total ash and acid-insoluble ash are not more than 12.0%, 15.0% and 8.0%, respectively.

In order to efficiently control the quality of the Tibetan medicine Gentianae Szechenyii Flos, the quality standard was established in this study. The tests of water content, total ash and ethanol-soluble extractives of the crude drugs were carried out based on the methods recorded in appendix of Chinese Pharmacopeia (2010 edition, volume 1). The TLC method was established by using reference drug and gentiournoside A as reference substance, and a mixture of ethyl acetate-methanol-water-formic acid (7: 1.5: 1: 0.2) as the developing solvent system on silica gel G TLC plate. The content of gentiournoside A was assayed by HPLC on a Ultimate XB-C18 (4.6 mm x 250 mm, 5 μm) column, using methanol-water (0.02% phosphoric acid) (52:48) as the mobile phase at a flow rate of 1.0 mL x min(-1). The column temperature is 25 degrees C and the detection wavelength is at 240 nm. As a result, gentiournoside A and the other constituents were separated and presented the same fluorescence light comparing with the reference substance on TLC detected under the UV light(366 nm). The methodology validation for the assay of gentiournoside A showed that it was in a good linear correlation in the range of 10.01-400.32 mg x L(-1) with the regression equation of Y = 1 539.5X - 33.339 (r = 0.999 7), and the average recovery was 99.68% (RSD 1.92%). The mass fractions of gentiournoside A, water content, ethanol-soluble extractives of 19 batches samples were varied in the ranges of 14.48-31.51 mg x g(-1), 11.25% -12.74% and 24.21% - 31.60%, respectively, and total ash was 4.64% - 6.12% detected from 10 batches samples. The recommended standards of quantitative indexes are that the mass fractions of gentiournoside A and extractives are not less than 15.0 mg x g(-1) (1.5%) and 21.0%, respectively; the water and total ash are not more than 13.0% and 6.0%, respectively.

The CO I gene sequences of Qianghuoyu, Pachytriton labiatus and Gehyra mutilata were achieved by PCR amplification and bi-directional sequencing. Furthermore, a pair of specific primers SJYW1 and SJYW2 in the non-conservative district were designed through sequence alignment. The PCR reaction condition was established by changing the annealing temperature and cycle numbers. The results showed that 350 bp DNA fragment was amplified from Qianghuoyu in PCR with annealed temperature at 54 °C and the cycle number was 25 cycles, whereas not any DNA fragment was amplified from P. labiatus and G. mutilata under the same reaction condition. This method is well-performed in the identification of Qianghuoyu for its excellent specificity and repeatability.

Objective: To study and summarize the clinical features of hypophosphatemia osteomalacia (HO) misdiagnosed as spondyloarthritis (SpA), aiming to analyze the reasons of misdiagnosis and improve the prognosis of such patients., Methods: A total of 26 cases of HO misdiagnosed as SpA were selected. Clinical features, laboratory tests, and image presentations were analyzed. Related literatures were reviewed., Results: (1) Clinical characters: 26 patients were included (12 males and 14 females) with a median age of 38 years (range 20-60). The mean disease duration was 3.2 years (range 0.75 to 10 years). Of all the patients, 15 were diagnosed as tumor-induced HO, 4 were long-term oral adefovir dipivoxil-related HO, 3 were associated with Fanconi syndrome, 2 were related to hyperparathyroidism, while 2 were Sjogren's syndrome complicated with renal tubular acidosis. All of the 26 patients presented with low back pain including 15 with night pain. The time of morning stiffness was about 30 minutes. Non-steroidal anti-inflammatory drugs were given to each patient whereas with poor efficacy, neither did other agents work well, such as glucocorticoids, disease modifying anti-rheumatic drugs and biologics. (2) LABORATORY FINDINGS: the platelet count and inflammatory markers such as erythrocyte sedimentation rate, C-reactive protein (CRP) were usually normal. The level of serum calcium was normal or slightly lower, nevertheless, all patients had hypophosphatemia and increased level of alkaline phosphatase (ALP). Patients with adefovir dipivoxil-related HO, Fanconi syndrome or Sjogren's syndrome complicated with renal tubular acidosis were characterized by hypokalemia, hyperchloremia and alkaline urine. Patients with hyperparathyroidism had elevated parathyroid hormone (PTH). Positive antinuclear antibodies (ANA) (titer ≥ 1: 320), anti-SSA/SSB antibodies were found in patients with Sjogren's syndrome. (3) Radiographic features: sacroiliac joint lesions were found in X-ray, CT, positron emission tomography (PET-CT) or MRI, however the lesions in sacrum or ilium were predominant rather than in joints. Abnormal bone imaging in ribs, long bones and soft tissues in addition to joints could be detected by bone scintigraphy., Conclusion: HO is not uncommon in daily practice. Besides SpA, other diseases should be considered in the setting of low-back pain and diseased sacroiliac joints. Comprehensive screening of bone metabolic parameters contributes to the timely diagnosis of HO.

Neurofibromas are benign nerve sheath tumors that arise from the nonmyelinating Schwann cells. Generally, neurofibromas can be categorized into dermal and plexiform subtypes. The former subtype is usually associated with a lone peripheral nerve in the integumentary system, while plexiform tumors are associated with many nerve bundles and can originate internally. Rarely, the plexiform tumors can undergo malignant transformation. Neurofibromas are usually found in individuals with neurofibromatosis, which is an autosomal dominant disease. On occasion, an isolated neurofibroma can transpire without being associated with neurofibromatosis. Mostly, these solitary tumors tend to occur in the gastrointestinal system, and neurofibromas of the head and neck are not uncommon, but very rarely they have been reported to occur in the temporal fossa. In this report, we describe a case of a solitary neurofibroma arising from the temporal fossa.

Objective: To investigate spinemagnetic resonance imaging(MRI) findings in patients with axial spondyloarthritis (SpA) and to analyze the correlation between imaging and clinical manifestation., Methods: The clinical data of patients with axial SpA were recorded. All patients underwent whole spine MRI scanning. The MRI findings of spinal involvement were explored. Moreover, the correlation between lesions in spinal MRI and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), nocturnal pain visual analogue scale (VAS) score, back pain VAS score, global disease activity VAS score, Ankylosing Spondylitis Disease Activity score (ASDAS), erythrocyte sedimentation rate, C-reactive protein was analyzed., Results: Thirty-three patients with axial SpA were included in this study. The image abnormalities of the spine were confirmed in 29 axial SpA patients by MRI, including Romanus lesion, Andersson lesion, the inflammation of facet joints and syndesmophyte. In correlation study, BASMI was positively correlated to the numbers of acute Romanus lesions, chronic Romanus lesions, chronic Andersson lesions and whole spinal lesions(r = 0.440, P < 0.05; r = 0.483, P < 0.05; r = 0.421, P < 0.05; r = 0.589, P < 0.05 respectively). There was a statistically significant correlation between chronic Andersson lesions and BASFI(r = 0.392, P < 0.05). But no significant associations were found between MRI lesions and other clinical findings., Conclusions: MRI lesions in axial SpA were associated with findings reflecting the spinal function, which can better guide the clinical treatment.

Fracturing by ductile damage occurs quite naturally in metal forming processes, and ductile fracture of strain-softening alloy, here 42CrMo steel, cannot be evaluated through simple procedures such as tension testing. Under these circumstances, it is very significant and economical to find a way to evaluate the ductile fracture criteria (DFC) and identify the relationships between damage evolution and deformation conditions. Under the guidance of the Cockcroft-Latham fracture criteria, an innovative approach involving hot compression tests, numerical simulations, and mathematic computations provides mutual support to evaluate ductile damage cumulating process and DFC diagram along with deformation conditions, which has not been expounded by Cockcroft and Latham. The results show that the maximum damage value appears in the region of upsetting drum, while the minimal value appears in the middle region. Furthermore, DFC of 42CrMo steel at temperature range of 1123~1348 K and strain rate of 0.01~10 s(-1) are not constant but change in a range of 0.160~0.226; thus, they have been defined as varying ductile fracture criteria (VDFC) and characterized by a function of temperature and strain rate. In bulk forming operations, VDFC help technicians to choose suitable process parameters and avoid the occurrence of fracture.

Background: The generation of harmful reactive oxygen species (ROS) induced by UVB irradiation could induce cell apoptosis and change the cell cycle. 6A,6A'-dicyclohexylamine-6B,6B'-diselenide-bis-β-cyclodextrin (6-CySeCD) is a novel glutathione peroxidase (GPx; EC 1.11.1.9) mimic. The aim of this study was to investigate the anti-oxidative effects of 6-CySeCD in cultured immortalised human keratinocyte cells (HaCaT)., Methods: HaCaT cells were treated with 30 mJ/cm(2) UVB to establish a damage model. The cultured HaCaT cells were randomly assigned to the control, UVB and treatment groups. The treatment group was incubated with 20 μmol/L of GPx mimics before UVB irradiation. Cell viability was detected by (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, the level of lipid peroxidation was determined by the formation of malondialdehyde (MDA), DNA fragmentation was observed using agarose gel electrophoresis and the levels of intracellular ROS and cell cycle progression were measured by flow cytometry., Results: The levels of cytotoxicity, intracellular ROS, lipid peroxidation and oxidative DNA damage significantly increased after UVB irradiation in the HaCaT cells. UVB irradiation caused pre-G1 -phase arrest in HaCaT cells and significantly reduced the number of HaCaT cells in the S phase. The GPx mimics 6-CySeCD and 2-phenyl-l,2-benzisoselenazol-3(2H)-one (ebselen) significantly blocked UVB-induced apoptosis and changed the cell cycle of the HaCaT cells. The blocked effect of pretreatment 6-CySeCD in UVB-irradiated HaCaT cells was better than that of pretreatment with ebselen., Conclusion: 6-CySeCD can relieve the damage induced by UVB irradiation in HaCaT cells., (© 2012 The Authors. Australasian Journal of Dermatology © 2012 The Australasian College of Dermatologists.)