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Kai Dong,1,2 Shu-Jing Deng,2 Bin-Yang He,2 Zi-Yang Guo,2 Ze-Lin Guan,2 Xue Leng,2 Rui-Rui Ma,2 Dan-Yang Wang,2 Jian-Feng Xing,2 Cui-Yu You1 1Department of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2School of Pharmacy, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of ChinaCorrespondence: Jian-Feng Xing, School of Pharmacy, Xi’an Jiaotong University, 76 Yanta West Road, Xi’an, 710061, Shaanxi, People’s Republic of China, Tel +86-29-82655139, Fax +86-29-82655139, Email xajdxjf@mail.xjtu.edu.cn Cui-Yu You, Department of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China, Tel +86-29-85323241, Fax +86-29-85323240, Email ycy720123@163.comBackground: As the first-line drug to treat ulcerative colitis (UC), long-term use of glucocorticoids (GCs) produces severe toxic and side effects. Local administration as enema can increase the local GCs concentrations and reduce systemic exposure to high oral doses by directly delivering GCs to the inflammation site in the distal colorectum. However, UC patients are often accompanied by diarrhea, leading to the short colonic residence time of GCs and failure to exert their function fully.Purpose: A kind of mucoadhesive nanoparticles (NPs) loading different dexamethasone derivatives (DDs) were developed, which could attach to the positively charged inflammatory colonic mucosa through electrostatic adsorption after administered by enema, thereby improving the local concentration and achieving effective targeted therapy for UC.Methods: Two DDs, dexamethasone hemisuccinate and dexamethasone phosphate, were synthesized. In NPs preparation, The core PEI-DDs NPs were built by the electrostatic adsorption of DDs and the cationic polymer polyethyleneimine (PEI). Then, the natural polyanionic polysaccharide sodium alginate (SA) was electronically coated around NPs to construct the final SA-PEI-DDs NPs, followed by the in vitro stability and release tests, in vitro and in vivo colonic mucosal adhesion tests. In the in vivo anti-UC test, the experimental colitis mice were induced by 2,4,6-trinitrobenzenesulfonic acid. The body weight and disease activity index changes were measured, and the myeloperoxidase activity, pro-inflammatory cytokines concentration, and hematoxylin and eosin staining were also investigated to evaluate the therapeutic effect of NPs.Results: The structures of two DDs were demonstrated by 1H-NMR and MS. Both NPs were negatively charged and achieved high loading efficiency of DDs, while their particle sizes were significantly different. NPs showed good stability and sustained release properties in the simulated colonic environment. Moreover, the negative charge on the of NPs surface made them easier to adhere to the positively charged inflammatory colonic mucosa, thereby enhancing the enrichment and retention of DDS in the colitis site. Furthermore, the NPs exhibited better therapeutic effects than free Dex on the experimental colitis mice induced by TNBS through the enema rectal.Conclusion: These results indicated the mucoadhesive NPs as a kind of novel nano-enema showed great potential to achieve efficient treatment on UC.Keywords: ulcerative colitis, glucocorticoids, mucoadhesive, polyethyleneimine, sodium alginate

Inflammatory bowel disease (IBD) is associated with elevated levels of reactive oxygen species (ROS) and an increased expression of proinflammatory cytokines. Anti-inflammatory drugs, monoclonal antibodies, and immunomodulators are commonly employed to control the inflammatory response in the management of IBD. Here, a copper and tannic acid (TA) coordination nanozyme (CuTA) loaded with sulfasalazine (SSZ-CuTA) is synthesized for the treatment of IBD by simultaneous scavenging ROS and immunosuppression. The CuTA exhibits both dismutase-like activity and catalase-like activity, making it efficient at scavenging ROS. These nanozymes can efficiently traverse gastric acid and subsequently exert their effects within the intestinal tract. It is verified that SSZ-CuTA can restore intestinal mucosal and goblet cells to a healthy state by effectively eliminating ROS and reducing the pro-inflammatory factors in a mouse IBD model. Overall, the SSZ-CuTA will offer a promising alternative treatment for patients suffering from IBD where excessive ROS and high inflammation coexist., (© 2024 Wiley‐VCH GmbH.)

This study aimed to explore the mechanism by which Zn retards Fe toxicity by analyzing the morphological, photosynthetic, and chloroplast physiological parameters of wheat seedlings treated with either single or combined Zn and Fe. Different behavior of the seedlings was observed under untreated and treated conditions. The most discriminating quantitative traits were associated with leaf area, biomass dry mass and fresh mass, net photosynthetic rate, intercellular CO 2 concentration, stomatal conductance, transpiration rate of seedlings, Hill reaction, Mg 2+ -ATPase and Ca 2+ -ATPase activities, malondialdehyde and O 2 ·- contents, and glutathione reductase, ascorbate peroxidase, peroxidase, and superoxide dismutase activities and their gene expression in the seedling chloroplast. The obtained findings suggest the important function of an appropriate Zn concentration in preventing Fe toxicity. Therefore, a thorough evaluation of the effects of Zn on Fe-stressed plant growth is beneficial for sustainable agriculture., Competing Interests: The authors declare that they have no conflict of interest., (Copyright: © 2024 Xu et al.)

Pseudomonas plecoglossicida is one of most important pathogenic bacterial species in large yellow croaker and several other commercially valuable fish species. In our previous study, a GacS deficient mutant (ΔgacS) was constructed and its virulence showed substantially attenuated. In present study, the safety, immunogenicity and protective effect of the ΔgacS were evaluated in large yellow croaker as a live-attenuated vaccine candidate. It was shown that the ΔgacS strain exhibited good safety to large yellow croaker and there was no mortality or clinical symptoms observed in all fish that infected by ΔgacS strain with the doses range from 2 × 10 5 ～10 7  CFU per fish via intraperitoneal injection (IP) or immersion (IM), and almost all bacteria were cleaned up in the spleen of the fish at 14-day post infection. Specific antibodies could be detected at 7-day and 14-day post infection by direct agglutination method, and the valences of antibodies and bactericidal activities of the serum were significant increased with vaccination doses and vaccination time. Moreover, the expressions of some molecules and cytokines involved in specific immune responses were detected in the ΔgacS strain immunization group and control group. After challenged by the wild-type (WT) strain XSDHY-P, the relative percentage survival (RPS) showed highly correlated with the immunized dosage regardless of vaccination methods. It showed that the RPS of the IP groups were 39.47 %, 57.89 %, 71.05 % with the immune dosage in a descending order, respectively, and the RPS of the IM groups were 26.31 %, 36.84 %, 76.31 % with the immune dosage in a descending order, respectively. In summary, the ΔgacS strain exhibited safety and good protective effect to large yellow croaker and was a potential live vaccine candidate., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Context: To investigate how short sleep duration (SSD) during pregnancy is related to neurodevelopmental delays in offspring, we aimed to inform pregnancy sleep guidelines and promote maternal health and child development., Objective: To identify the associations between SSD during pregnancy and offspring neurodevelopmental delay and to determine whether fetal glucose metabolism plays a role in SSD and neurodevelopmental delays., Methods: This cohort study followed 7059 mother-child pairs from the Maternal & Infants Health in Hefei cohort, and collected sleep data during pregnancy via the Pittsburgh Sleep Quality Index at weeks 24 to 28 and 32 to 36. Neurodevelopmental outcomes from 6 to 36 months postpartum were assessed via the Denver Developmental Screening Test-II and the Gesell Development Diagnosis Scale. Cox proportional hazard regression was used to analyze the link between maternal SSD and neurodevelopmental delay risk. Mediation analysis was used to evaluate the role of cord blood serum C-peptide levels. Three hospitals and children's health centers in Hefei were involved., Results: The stratified analysis revealed a significant association between mothers with SSD during midpregnancy and neurodevelopmental delay in boys (adjusted HR 2.05, 95% CI 1.29, 3.25). Cord blood marker analysis revealed a positive relationship between cord blood serum C-peptide levels and neurodevelopmental delay in offspring (RR 0.04, 95% CI 0.00, 0.08). The proportion of the association between SSD and neurodevelopmental delay mediated by cord blood C-peptide was 11.05%., Conclusion: Maternal SSD during pregnancy was continuously associated with an increased incidence of neurodevelopmental delay with sex differences among offspring. This association may be mediated in part by increased higher levels of cord C-peptide., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Long noncoding RNAs (lncRNAs) play critical roles in the carcinogenesis and progression of cancers. However, the role and mechanism of the pseudogene lncRNA PIN1P1 in gastric carcinoma remain unclear. The expression and effects of lncRNA PIN1P1 in gastric cancer were investigated. The transcriptional regulation of CREB1 on PIN1P1 was determined by ChIP and luciferase assays. The mechanistic model of PIN1P1 in gastric cancer was further explored by RNA pull-down, RIP and western blot analysis. PIN1P1 was overexpressed in gastric cancer tissues, and upregulated PIN1P1 predicted poor prognosis in patients. CREB1 was directly combined with the promoter region of PIN1P1 to promote the transcription of PIN1P1. CREB1-mediated enhanced proliferation, migration and invasion could be partially reversed by downregulation of PIN1P1. Overexpressed PIN1P1 promoted the proliferation, migration and invasion of gastric cancer cells, whereas decreased PIN1P1 showed the opposite effects. PIN1P1 directly interacted with YBX1 and promoted YBX1 protein expression, leading to upregulation of PIN1, in which E2F1 may be involved. Silencing of YBX1 during PIN1P1 overexpression could partially rescue PIN1 upregulation. PIN1, the parental gene of PIN1P1, was elevated in gastric cancer tissues, and its upregulation was correlated with poor patient outcomes. PIN1 facilitated gastric cancer cell proliferation, migration and invasion. To sum up, CREB1-activated PIN1P1 could promote gastric cancer progression through YBX1 and upregulating PIN1, suggesting that it is a potential target for gastric cancer., (© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

We report the observation of a set of coherent high frequency electromagnetic fluctuations that leads to a turbulence induced self-regulating phenomenon in the DIII-D high bootstrap current fraction plasma. The fluctuations have frequency of 130-220  kHz, the poloidal wavelength and phase velocity are 16-30  m^{-1} and ∼30  km/s, respectively, in the outboard midplane with the estimated toroidal mode number n∼5-9. The fluctuations are located in the internal transport barrier (ITB) region at large radius and are experimentally validated to be kinetic ballooning modes (KBM). Quasilinear estimation predicts the KBM to be able to drive experimental particle flux and non-negligible thermal flux, suggesting its significant role in regulating the ITB saturation.

Objective: To investigate the distribution and antimicrobial susceptibility of causative microorganisms recovered from patients with intra-abdominal infections (IAIs)., Methods: A total of 2,926 bacterial and fungal strains were identified in samples collected from 1,679 patients with IAIs at the Peking Union Medical College Hospital between 2011 and 2021. Pathogenic bacteria and fungi were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Antimicrobial susceptibility testing (AST) was performed using the VITEK 2 compact system and the Kirby-Bauer method. AST results were interpreted based on the M100-Ed31 clinical breakpoints of the Clinical and Laboratory Standards Institute., Results: Of the 2,926 strains identified, 49.2%, 40.8%, and 9.5% were gram-negative bacteria, gram-positive bacteria, and fungi, respectively. Escherichia coli was the most prevalent pathogen in intensive care unit (ICU) and non-ICU patients; however, a significant decrease was observed in the isolation of E. coli between 2011 and 2021. Specifically, significant decreases were observed between 2011 and 2021 in the levels of extended-spectrum β-lactamase (ESBL)-producing E. coli (from 76.9% to 14.3%) and Klebsiella pneumoniae (from 45.8% to 4.8%). Polymicrobial infections, particularly those involving co-infection with gram-positive and gram-negative bacteria, were commonly observed in IAI patients. Moreover, Candida albicans was more commonly isolated from hospital-associated IAI samples, while Staphylococcus epidermidis had a higher ratio in community-associated IAIs. Additionally, AST results revealed that most antimicrobial agents performed better in non-ESBL-producers than in ESBL-producers, while the overall resistance rates (56.9%-76.8%) of Acinetobacter baumanmii were higher against all antimicrobial agents than those of other common gram-negative bacteria. Indeed, Enterococcus faecium , Enterococcus faecalis , S. epidermidis , and S. aureus were consistently found to be susceptible to vancomycin, teicoplanin, and linezolid. Similarly, C. albicans exhibited high susceptibility to all the tested antifungal drugs., Conclusion: The distribution and antimicrobial susceptibility of the causative microorganisms from patients with IAIs were altered between 2011 and 2021. This finding is valuable for the implementation of evidence-based antimicrobial therapy and provides guidance for the control of hospital infections., (Copyright © 2023 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Background: Gastric cancer is the fourth leading cause of cancer-related deaths worldwide. And patient outcomes are poor due to tumor relapse and metastasis. To develop new therapeutic strategies, it is of great importance to explore the mechanism underlying the progression of gastric cancer., Methods: Primary gastric cancer samples with lymph node metastases (LNM) and without LNM were subjected to mRNA microarray assay. The differentially expressed genes were confirmed by RT-qPCR. HRCT1 protein expression was further detected using an immunohistochemistry (IHC) assay. In vitro and in vivo assays were performed to investigate the role of HRCT1 in tumor invasion, metastasis, and proliferation. The expressions of the downstream target genes of HRCT1 were detected by microarray, RT-qPCR and Western blot assays. Dual-luciferase reporter and Western blot assays were carried out to identify miRNAs target to HRCT1., Results: HRCT1 was upregulated in gastric cancer, and high expression of HRCT1 was associated with poor overall survival (OS) and disease-free survival (DFS). Moreover, HRCT1protein expression was an independent predictor for poor OS and DFS. HRCT1 could promote gastric cancer cells' migration, invasion, and proliferation in vitro as well as tumor metastasis and growth in vivo. Notably, our data showed that HRCT1 promoted gastric cancer progression by activating the ERBB2-MAPK signaling pathway. At least partially, the expression of HRCT1 could be negatively regulated by miR-124-3p., Conclusions: The upregulated expression of HRCT1 predicts poor survival for patients with gastric cancer. HRCT1 promotes tumor progression by activating the ERBB2-MAPK pathway. HRCT1, negatively regulated by miR-124-3p, may be a potential therapeutic target for patients with gastric cancer., (© 2023. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Breast cancer (BC) is the most common malignant tumor in women worldwide. Metastasis is the main cause of BC-related death. The specific mechanism underlying BC metastasis remains obscure. Recently, PRSS22 was discovered to be involved in tumor development, however, its detailed biological function and regulatory mechanism in BC are unclear. Here, we characterized that PRSS22 expression is upregulated in BC tissues compared with non-tumorous breast tissues. Dual luciferase assays, bioinformatics analyses and chromatin immunoprecipitation (ChIP) assays indicated that transcription factor E2F1 directly binds to the PRSS22 promoter region and activates its transcription. Functionally, upregulation of PRSS22 promoted invasion and metastasis of BC cells in vitro and in vivo, whereas knockdown of PRSS22 inhibited its function. Mechanistically, the combination of PRSS22 and ANXA1 protein in BC cells was first screened by protein mass spectrometry analysis, and then confirmed by co-immunoprecipitation (Co-IP) and western blot assays. Co-overexpression of PRSS22 and ANXA1 could promote BC cell migration and invasion. We further demonstrated that PRSS22 promotes the cleavage of ANXA1 and in turn generates an N-terminal peptide, which initiates the FPR2/ERK signaling axis to increase BC aggressiveness., (© 2022. The Author(s).)

Kudoa (Myxosporea: Multivalvulida) parasites are critical pathogens in marine and freshwater fish associated with significant economic losses and reduced market prices caused by post-mortem myoliquefaction or numerous cysts on muscles. In the present study, large yellow croakers infected by Kudoa were found during fish disease surveillance in China in November 2020 and used for morphological observation and characterization using light DIC microscopy and electron microscopy. Numerous creamy-white oval plasmodia were observed in muscles and on the surface of brain cartilage, gill arches, and serosal surfaces. The spores were considerably longer and thicker than previously reported Kudoa , with protruding polar filaments (PFs) in the mature spores, fingertip-shaped apical projections (APs), and polar capsules. Phylogenetic analyses with SSU rDNA, LSU rDNA, and mitochondrial DNA showed that the Kudoa -infected sample (LcK-2020) had the highest similarity to Kudoa iwatai reported in Japan. Based on the morphological characterization and phylogenetic analysis, it could be concluded that the sample LcK-2020 was infected by Kudoa iwatai , which would be the first report of Kudoa iwatai infection in large yellow croaker in China.

A novel deep eutectic solvent-magnetic molecularly imprinted polymer (DES-MMIP) for the specific removal of oxalic acid (OA) was prepared by an environmentally friendly deep eutectic solvent, consisting of betaine, citric acid, and glycerol, which acted as the functional monomer for polymerization. The structure and morphology of DES-MMIPs were studied by X-ray diffraction, scanning and transmission electron microscopy, thermal gravimetric analysis, Fourier transform infrared spectroscopy, and vibrating sample magnetometer. DES-MMIPs had a core-shell structure, with magnetic iron oxide as the core, and showed good thermal stability and high adsorption capacity (18.73 mg/g) for OA. The adsorption process of OA by DES-MMIPs followed the pseudo-second-order kinetic model and Langmuir isotherm model. DES-MMIPs had significant selectivity for OA and their imprinting factor was 3.26. When applied to real samples, high performance liquid chromatography analysis showed that DES-MMIPs could remove OA from both spinach and blood serum. These findings provide potential methods for removal of OA from vegetables and for specific removal of OA in renal dialysis., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)

Long noncoding RNAs (lncRNAs) are dysregulated in different cancer types, and thus have emerged as important regulators of the initiation and progression of human cancers. However, the biological functions and the underlying mechanisms responsible for their functions in gastric cancer (GC) remain poorly understood. Here, by lncRNA microarray, we identified 1414 differentially expressed lncRNAs, among which THAP7-AS1 was significantly upregulated in GC tissues compared with non-tumorous gastric tissues. High expression of THAP7-AS1 was correlated with positive lymph node metastasis and poorer prognosis. SP1, a transcription factor, could bind directly to the THAP7-AS1 promoter region and activate its transcription. Moreover, the m 6 A modification of THAP7-AS1 by METTL3 enhanced its expression depending on the "reader" protein IGF2BP1-dependent pathway. THAP7-AS1 promoted GC cell progression. Mechanistically, THAP7-AS1 interacted with the 1-50 Amino Acid Region (nuclear localization signal) of CUL4B through its 1-442 nt Sequence, and it promoted interaction between nuclear localization signal (NLS) and importin α1, and improved the CUL4B protein entry into the nucleus, repressing miR-22-3p and miR-320a expression by CUL4B-catalyzed H2AK119ub1 and the EZH2-mediated H3K27me3, subsequently activating PI3K/AKT signaling pathway to promote GC progression. Moreover, LV-sh-THAP7-AS1 treatment could suppress GC growth, invasion and metastasis, indicating that THAP7-AS1 may act as a promising molecular target for GC therapies. Taken together, our results show that THAP7-AS1, transcriptionally activated by SP1 and then modified by METTL3-mediated m6A, exerts oncogenic functions, by promoting interaction between NLS and importin α1 and then improving the CUL4B protein entry into the nucleus to repress the transcription of miR-22-3p and miR-320a., (© 2021. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)

Breast cancer (BC) is the most common cancer in women worldwide, and the exploration of aberrantly expressed genes might clarify tumorigenesis and help uncover new therapeutic strategies for BC. Although RGMA was recently recognized as a tumor suppressor gene, its detailed biological function and regulation in BC remain unclear. Herein, we found that RGMA was downregulated in BC tissues compared with non-tumorous breast tissues, particularly in metastatic BC samples, and that patients with low RGMA expression manifested a poorer prognosis. Furthermore, DNMT1 and DNMT3A were found to be recruited to the RGMA promoter and induced aberrant hypermethylation, resulting in downregulation of RGMA expression in BC. In contrast, RGMA overexpression suppressed BC cell proliferation and colony-formation capabilities and increased BC cell apoptosis. Furthermore, RGMA knockdown accelerated BC cell proliferation and suppressed cellular apoptosis in vitro and in vivo. Reversal of RGMA promoter methylation with 5-Aza-CdR restored RGMA expression and blocked tumor growth. Overall, DNMT1- and DNMT3A-mediated RGMA promoter hypermethylation led to downregulation of RGMA expression, and low RGMA expression contributed to BC growth via activation of the FAK/Src/PI3K/AKT-signaling pathway. Our data thus suggested that RGMA might be a promising therapeutic target in BC., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

The development of effective drug-loaded dressings has been considered a hot research topic for biomedical therapeutics, including the use of botanical compounds. For wound healing, adequate dressings can provide a good microenvironment for drug release, such as lidocaine. Biological macromolecular materials such as alginate show excellent properties in wound management. This study involves the preparation and evaluation of biocompatible multilayered-structure microspheres composed of chitosan, porous gelatin, and calcium alginate microspheres. The multilayered structure microspheres were named chitosan@ porous gelatin@ calcium alginate microspheres (CPAMs) and the drugs were rapidly released by the volume expansion of the calcium alginate microspheres. The in vitro release curve revealed that the peak release of lidocaine from CPAMs was reached within 18[Formula: see text]min. After 21[Formula: see text]min, the remaining lidocaine was then slowly released, and the active drug release was converted to a passive drug release phase. The initial release effect of lidocaine was much better than that reported in the published studies. Additionally, blood coagulation experiments showed that CPAMs coagulated blood in 60[Formula: see text]s, and the blood liquidity of the CPAMs group was worse than that of the woundplast group. Therefore, the coagulation characteristics of CPAMs were superior to the commonly used woundplast containing lidocaine healing gel. These study outcomes indicated that the CPAMs acted as fast-release dressings for faster pain control and better coagulation properties.

This paper addresses the robust stochastic finite-time and fixed-time chaos synchronization of two permanent magnet synchronous motors (PMSMs) in noise environment. The novel adaptive finite-time and fixed-time control schemes are implemented, respectively, which can not only ensure that the stochastic chaos synchronization of PMSMs can be achieved in a fast rate, but also determine the control gains successfully(not necessary to set them in advance). The sufficient conditions are derived in the light of the stochastic finite-time and fixed-time stability theories, where the upper bound of synchronization time can be estimated. Furthermore, the stochastic fixed-time synchronization can get rid of the dependence of initial conditions in PMSMs, which overcomes the critical deficiency of stochastic finite-time synchronization of PMSMs. Finally, simulation results demonstrate the validity of proposed theoretical analysis with comparisons., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 ISA. Published by Elsevier Ltd. All rights reserved.)

Long non-coding RNAs (lncRNAs) play important roles in cancer development and progression; however, their contributions to gastric cancer metastasis remain largely unknown. By lncRNA microarray screening, our study showed that 453 lncRNAs are dysregulated in gastric cancer tissues with or without lymph node metastasis, of which lnc-LEMGC ranks as one of the most significantly downregulated lncRNAs. Lnc-LEMGC inhibited cell migration and invasion both in vitro and in vivo, by combining with protein DNA-PKcs. Importantly, nucleotides 1300-1800 of lnc-LEMGC prevented DNA-PKcs phosphorylation of serine 2056 and partially abrogated the effects of downstream effectors, ErbB1, SRC and protein tyrosine kinase 2 (FAK), in the epidermal growth factor receptor (EGFR) pathway. The results of this study extend our knowledge of lncRNA's molecular mechanisms, in which lnc-LEMGC functions by directly suppressing the phosphorylation of its combined protein DNA-PKcs and inactivating the DNA-PKcs downstream EGFR signaling., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Among the IV-VI compounds, GeSe has wide applications in nanoelectronics due to its unique photoelectric properties and adjustable band gap. Even though modulation of its physical characteristics, including the band gap, by an external field will be useful for designing novel devices, experimental work is still rare. Here, we report a detailed anisotropic Raman response of GeSe flakes under uniaxial tension strain. Based on theoretical analysis, the anisotropy of the phonon response is attributed to a change in anisotropic bond length and bond angle under in-plane uniaxial strain. An enhancement in anisotropy and band gap is found due to strain along the ZZ or AC directions. This study shows that strain-engineering is an effective method for controlling the GeSe lattice, and paves the way for modulating the anisotropic electric and optical properties of GeSe.

Transferrin (Trf) is a new type of active drug targeting carrier and disease biomarker that regulates the balance of iron ions in human body. The recognition and isolation of Trf is of great significance for disease diagnosis and treatment. Thus, a new type of magnetic dual affinity epitope molecularly imprinted polymer coated on Fe 3 O 4 nanoparticles (Fe 3 O 4 @DEMIP) was successfully prepared for specific recognition of Trf. C-terminal nonapeptide and Trf glycan were selected as bi-epitope templates for metal chelation and boron affinity immobilization, respectively. 4-vinylphenylboric acid (4-VP), N-isopropyl acrylamide (NIPAM) and zinc acrylic were used as functional monomers. Results showed that Fe 3 O 4 @DEMIP exhibited excellent specific recognition ability adsorption capacity toward Trf, with an adsorption of 43.96 mg g -1 (RSD = 3.28%) and a more satisfactory imprinting factor (about 6.60) than that of other reported imprinting methods. In addition, Fe 3 O 4 @DEMIP displayed pH, temperature and magnetic sensitivity properties to realize temperature and pH-controlled recognition and release of target proteins and magnetic rapid separation. Furthermore, the Fe 3 O 4 @DEMIP coupled with high-performance liquid chromatography (HPLC) analysis was successfully used for specific recognition of Trf in biosamples. This study provides a reliable protocol for preparing metal chelation and boron affinity dual affinity bi-epitope molecularly imprinted polymers for synergistic and efficient recognition of biomacromolecules in the complex biological systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In this study, we aimed to explore the effects of iguratimod (IGU) combined with methotrexate (MTX) and hydroxychloroquine (HCQ) on bone mineral density (BMD) in patients with rheumatoid arthritis (RA). 76 patients who received IGU combined with MTX and HCQ were included in this retrospective study. After 48 weeks treatment of IGU combined with MTX and HCQ, the BMD at the L1-L4 ( p <0.01), left femoral neck ( p <0.01) and left total hip ( p <0.01) were significantly increased. Especially, the BMD at left femoral neck was significantly increased from baseline to week 24 ( p <0.05). With regard to inflammatory reaction, there were statistically significant reductions in the RF ( p <0.05), CRP ( p <0.05), ESR ( p <0.01), anti-CCP ( p <0.01) from baseline to week 48. The most common adverse events were gastrointestinal reaction and transaminase elevation. The combination of IGU, MTX and HCQ could significantly improve the BMD and restrain inflammatory reaction. No additional adverse events were noticed in our research. This study provides valuable information for treatment of osteopenia in patients with RA.

The COVID-19 pandemic damaged crude oil markets and amplified the consequences of uncertainty stemming from the Russia-Saudi Arabia oil price war in March-April of 2020. We investigate the impacts of the oil price war on global crude oil markets. By doing so, we use the daily futures and spot prices in three major crude oil markets - West Texas Intermediate, European Brent, and Oman - to perform a systematic analysis of the impacts of the oil price war on them. The event study method, a well-established analytical tool to measure the impacts of a given event on markets, is used in this study. The results indicate that information leakage plays an important role in the impacts of the price war. The outbreak of and truce following the price war have asymmetrical impacts on the markets; negative impacts generated by information leakage during the outbreak are generally more durable than the positive ones it generated during the truce. Furthermore, the magnitude of the impacts on futures markets is negatively correlated with the time-to-maturity of futures. Finally, negative crude oil prices affect West Texas Intermediate crude oil markets the most. Our findings generally show that market participants could perceive and assimilate market changes and adjust their expectations, which restrained the impacts that should have occurred within the oil price war., (© 2021 Elsevier B.V. All rights reserved.)

Early identification of individuals susceptible to idiosyncratic drug-induced liver injury (IDILI) is a challenging unmet demand. Diclofenac, one of the most widely available over-the-counter drugs for pain management worldwide, may induce liver dysfunction, acute liver failure, and death. Herein, we report that diclofenac-related hepatobiliary adverse reactions occurred more frequently in cases with immune activation. Furthermore, experiments with rats demonstrated divergent hepatotoxicity responses in individuals exposed to diclofenac, and modest inflammation potentiated diclofenac-induced liver injury. Susceptible rats had unique plasma metabolomic characteristics, and as such, the metabolomic approach could be used to distinguish susceptible individuals. The 23 identified susceptibility-related metabolites were enriched by several metabolic pathways related to acute-phase reactions of immunocytes and inflammatory responses, including sphingolipid, tyrosine, phenylalanine, tryptophan, and lipid metabolism pathways. This finding implies a mechanistic role of metabolic and immune disturbances affects susceptibility to diclofenac-IDILI. Further nine metabolite biomarkers with potent diagnostic capabilities were identified using receiver operating characteristic curves. These findings elucidated the potential utility of metabolomic biomarkers to identify individuals susceptible to drug hepatotoxicity and the underlying mechanism of metabolic and immune disturbances occurring in IDILI., 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 Tu, Gao, Song, Niu, Ma, Zhou, He, Xiao and Wang.)

In this work, an efficient and sensitive magnetic molecularly imprinted polymer with zein and deep eutectic solvents (ZDM-MIPs) was designed and synthesized to exclusively adsorb and detect aspartame (ASP). We used zein, together with deep eutectic solvents (DESs) and Fe 3 O 4 as the cross-linker, functional monomer and support material, respectively. A magnetic glassy carbon electrode (MGCE) modified with ZDM-MIPs was used for selective recognition of ASP. The electrochemical response of the ZDM-MIPs-MGCE for quantification of ASP was evaluated with a portable electrochemical detection station with differential pulse voltammetry and cyclic voltammetry. The responses of ZDM-MIPs-MGCE signified a good linear relationship with ASP concentrations in the range of 0.1-50 μg mL -1 . The sensor systems showed good accuracy and precision, with recovery percentages between 84% and 107%. These results suggested that the obtained ZDM-MIPs exhibited good adsorption performance for ASP in soft drinks, and this method could be used to determine ASP content in actual food samples., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Fuke Qianjin Capsule (FKQJ) is a common TCM compound formula in the treatment of gynecological inflammation-related diseases. This study intends to explore and establish a bioassay method to further improve its quality control. The bioassay method for the determination of anti-inflammatory biopotency was established based on its inhibitory activity on recombinant human cyclooxygenase-2 (COX-2), an active target of FKQJ in the treatment of female pelvic inflammatory disease. We firstly established chemical fingerprint of 20 batches of FKQJ by ultra-high-performance liquid chromatography to identify the components and analyze the chemical similarities. The similarity within different batches of FKQJ was relatively high. The values of similarity of the 19 batches were between 0.973 and 0.995, while one batch's similarity value was 0.813. Celecoxib, a selective inhibitor of COX-2, was chosen as the positive control drug in COX-2 activity assay to establish an anti-inflammatory biopotency detection method based on parallel line test of qualitative response. The methodological investigation showed that the method possessed good repeatability and precision. Secondly, the anti-inflammatory biopotency of 20 batches of FKQJ for inhibiting COX-2 was determined. The results showed that the biopotency of different batches of FKQJ ranged from 676 U/ μ g to 1310 U/ μ g, with average value of 918 U/ μ g and RSD of 16.7%. Based on multiple linear regression analysis, we found that three contents were highly correlated with the anti-inflammatory biopotency, while chlorogenic acid was validated of the strongest anti-inflammatory activity in vitro. Compared with chemical detection, bioassay can better reflect the quality fluctuation of different batches of products and correlate the known pharmacodynamic targets. The supplement of the bioassay method based on chemical evaluation is helpful to improve the quality control ability of Chinese patent medicine and ensure its clinical efficacy is stable and controllable., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Run-ran Ma et al.)

Gastric cancer (GC) is one of the most common malignant neoplasms. Invasion and metastasis are the main causes of GC-related deaths. Recently, kinesins were discovered to be involved in tumor development. The aim of this study was to elucidate the roles of kinesin superfamily protein 26A (KIF26A) in GC and its underlying molecular mechanism in regulating tumor invasion and metastasis. Using real-time quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC), we showed that KIF26A expression was lower in GC tissues without lymph node metastasis (LNM) than in nontumorous gastric mucosa, and even lower in GC tissues with LNM than in GC tissues without LNM. Functional experiments showed that KIF26A inhibited migration and invasion of GC cells. We further identified focal-adhesion kinase (FAK), phosphatidylinositol 3-kinase regulatory subunit alpha (PI3KR1), VAV3, Rac1 and p21-activated kinase 2, and β-PAK (PAK3) as downstream effectors of KIF26A in the focal-adhesion pathway, and we found that KIF26A could regulate FAK mRNA expression through inhibiting c-MYC by MAPK pathway. c-MYC could bind to the promoter of FAK and activate FAK transcription. Moreover, we found that KIF26A-mediated inactivation of the focal-adhesion pathway could reduce the occurrence of the epithelial-to-mesenchymal transition (EMT) by increasing expression of E-cadherin and reducing that of Snail. Luciferase assays and Western blotting revealed that miR-19a and miR-96 negatively regulate KIF26A. Finally, we found that decreased expression of KIF26A has been positively correlated with histological differentiation, Lauren classification, LNM, distal metastasis, and clinical stage, as well as poor survival in patients with GC. These data indicate that KIF26A could inhibit GC migration and invasion by regulating the focal-adhesion pathway and repressing the occurrence of EMT.

Solid-liquid interface is a key concept of many research fields, enabling numerous physical phenomena and practical applications. For example, electrode-electrolyte interfaces with electric double layers have been widely used in energy storage and regulating physical properties of functional materials. Creating a specific interface allows emergent functionalities and effects. Here, we show the artificial control of ferroelectric-liquid interfacial structures to switch polarization states reversibly in a van der Waals layered ferroelectric CuInP 2 S 6 (CIPS). We discover that upward and downward polarization states can be induced by spontaneous physical adsorption of dodecylbenzenesulphonate anions and N,N-diethyl-N-methyl-N-(2-methoxyethyl)-ammonium cations, respectively, at the ferroelectric-liquid interface. This distinctive approach circumvents the structural damage of CIPS caused by Cu-ion conductivity during electrical switching process. Moreover, the polarized state features super-long retention time (>1 year). The interplay between ferroelectric dipoles and adsorbed organic ions has been studied systematically by comparative experiments and first-principles calculations. Such ion adsorption-induced reversible polarization switching in a van der Waals ferroelectric enriches the functionalities of solid-liquid interfaces, offering opportunities for liquid-controlled two-dimensional ferroelectric-based devices.

Paclitaxel (PTX) is a powerful anticancer natural product, with its separation and purification having been widely studied. In this work, new molecular imprinted polymers (MIPs) using deep eutectic solvents (DESs) with different molar ratios were prepared as functional monomers. These were then used as adsorbents in solid phase extraction (SPE) for the separation of PTX from its structural analogs. The polymers were characterized by energy disperive X-rays (EDX), scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and fourier transform infrared spectroscopy (FT-IR). The results suggested that the formative regular DES-MIPs had an even pore-size distribution and a large specific surface area. The dynamic adsorption and static adsorption showed that the DES-MIPs had excellent adsorption performance, with a maximum adsorption capacity and optimum adsorption time of 87.08 mg/g and 180 min, respectively. The selective adsorption experiments showed that the material had outstanding selectivity, and the maximum selectivity factor was 6.20. For stability, after six consecutive adsorption and desorption cycles, the DES-MIPs maintained the perfect stability and reusability. Furthermore, the fabricated SPE column was successfully utilized for extracting and eluting PTX. This study provides a reliable protocol for the separation and purification PTX from its structural analogs and the DES-MIPs materials have excellent potential application value in pharmaceutical industry., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Gastric cancer (GC) is one of the most common cancers around the world. Searching for specific gene expression changes during the development of GC could help identify potential therapy targets. We previously showed that the histone code reader SPIN1 may act as an oncogene in breast cancer. At present, the biological function and regulation of SPIN1 in GC remain unclear. Here, we demonstrate that SPIN1 is upregulated in GC tissues, compared with nontumorous gastric tissues. Increased expression of SPIN1 is closely associated with poor prognosis for patients with GC. Increased SPIN1 expression enhances GC cell proliferation, migration, and invasion and promotes cell cycle progression. Mechanically, SPIN1 sustains GC cell proliferation via activation of the MDM2-p21-E2F1 signaling pathway by binding to H3K4me3 of the MDM2 promoter region. Interestingly, E2F1 could directly bind to the SPIN1 promoter and activate its transcription, thus forming a positive feedback loop. Our data suggest that SPIN1 plays an important role in the development of GC and could be used as a promising prognostic biomarker and therapeutic target for GC., (© 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)

Biocompatible magnetic molecularly imprinted polymers (BMMIPs) were prepared with Zein for the first time, and were used to enrich tetracycline compounds selectively. Innovative combination of BMMIPs and electrochemistry to obtain lower detection line to satisfy industrial detection demands. Using Zein as the crosslinking agent, the polymers were synthesized on the surface of Fe 3 O 4 particles. The scanning electron microscope, transmission electron microscope and X-ray diffraction technologies were used to characterize BMMIPs. Through optimization, BMMIPs attained large adsorption capacity (236.40 mg/g) with fast kinetics (40 min) and followed the Langmuir isotherm and pseudo-second-order kinetic models. BMMIPs had good recognition ability, the selective factors of oxytetracycline, chlortetracycline, doxycycline were 4.78, 4.23, and 3.39, respectively. Excellent linearity was attained in the range of 0.025-500 μg/mL, with low detection limits and low quantitation limits of 0.025 and 0.083 μg/mL. According to our exploring, BMMIPs was ideal materials for enrichment of tetracycline in complex biological samples., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Invasion and metastasis of gastric cancer after curative resection remain the most common lethal outcomes. However, our current understanding of the molecular mechanism underlying gastric cancer metastasis is far from complete. Herein, we identified TOR signaling pathway regulator (TIPRL) as a novel metastasis suppressor in gastric cancer through genome-wide gene expression profiling analysis using mRNA microarray. Decreased TIPRL expression was detected in clinical gastric cancer specimens, and low TIPRL expression was correlated with more-advanced TNM stage, distant metastasis, and poor clinical outcome. Moreover, TIPRL was identified as a direct target of miR-216a-5p and miR-383-5p. Functional study revealed that re-expression of TIPRL in gastric cancer cell lines suppressed their migratory and invasive capacities, whereas inverse effects were observed in TIPRL-deficient models. Mechanistically, TIPRL downstream effectors and signaling pathways were investigated using mRNA microarray. Gene expression profiling revealed that TIPRL could not modulate the downstream genes at transcriptional levels, thereby implying that the regulation might occur at the post-transcriptional levels. We further demonstrated that TIPRL induced phosphorylation/activation of AMPK, which in turn attenuated phosphorylation of mTOR, p70S6K, and 4E-BP1, thereby leading to inactivation of mTOR signaling and subsequent suppression of cell migration/invasion in gastric cancer. Taken together, TIPRL acts as a novel metastasis suppressor in gastric cancer, at least in part, through regulating AMPK/mTOR signaling, likely representing a promising target for new therapies in gastric cancer., (Copyright © 2020 Luan, Shi, Shi, Liu, Ma, Xu, Sun and Gao.)

Background: Accumulating evidence demonstrated that long noncoding RNAs (lncRNAs) played important regulatory roles in many cancer types. However, the role of lncRNAs in gastric cancer (GC) progression remains unclear., Methods: RT-qPCR assay was performed to detect the expression of HNF1A-AS1 in gastric cancer tissues and the non-tumourous gastric mucosa. Overexpression and RNA interference approaches were used to investigate the effects of HNF1A-AS1 on GC cells. Insight into competitive endogenous RNA (ceRNA) mechanisms was gained via bioinformatics analysis, luciferase assays and an RNA-binding protein immunoprecipitation (RIP) assay, RNA-FISH co-localisation analysis combined with microRNA (miRNA)-pulldown assay., Results: This study displayed that revealed expression of HNF1A-AS1 was associated with positive lymph node metastasis in GC. Moreover, HNF1A-AS1 significantly promoted gastric cancer invasion, metastasis, angiogenesis and lymphangiogenesis in vitro and in vivo. In addition, HNF1A-AS1 was demonstrated to function as a ceRNA for miR-30b-3p. HNF1A-AS1 abolished the function of the miRNA-30b-3p and resulted in the derepression of its target, PIK3CD, which is a core oncogene involved in the progression of GC., Conclusion: This study demonstrated that HNF1A-AS1 worked as a ceRNA and promoted PI3K/AKT signalling pathway-mediated GC metastasis by sponging miR-30b-3p, offering novel insights of the metastasis mechanism in GC.

Gastric cancer is one of the most common cancers in the world, and long non-coding RNAs (lncRNAs) play a crucial role in proliferation, metastasis, and invasion of gastric cancer. However, there are very few researches focusing on the effects of lncRNAs on metastatic gastric cancer. In this research, we identify one kind of lncRNA, called AK025387, which is highly expressed in metastatic gastric cancer samples compared with non-metastatic gastric cancer samples. The expression of AK025387 is significantly positively correlated with lymph node metastasis. The in situ hybridization demonstrates that AK025387 is located in both nucleus and cytoplasm, but mostly in cytoplasm. AK025387 promotes gastric cancer cells migratory and invasive ability, but it inhibits apoptosis in vitro . Furthermore, AK025387 regulates Raf-1, mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK), and extracellular signal-regulated kinase (ERK) and is involved in mitogen-activated protein kinase (MAPK) signaling pathway to perform its biological functions. We conclude that AK025387 is highly expressed in metastatic gastric cancer, and its biological functions suggest the potential of AK025387 to be a biomarker of metastatic gastric cancer., (Copyright © 2020 Sun, Zhang, Ma, Zhang, Tian, Liu, Liu and Gao.)

Background: Breast cancer is the most common cause of cancer-related death in women worldwide. MicroRNA (miRNA) ectopic expression has been reported to be involved in the regulation of gene expression in breast cancer. We screened several differentially expressed miRNAs associated with breast cancer chemoresistance, growth, and metastasis using a miRNA microarray. Increased expression of miR-4472 has been associated with larger breast tumors and chemoresistance. However, the biologic function of miR-4472 and its molecular mechanisms in cancer progression have not yet been reported., Materials and Methods: Real-time quantitative polymerase chain reaction was used to measure the expression of miR-4472 in breast cancer tissue and cell lines. The biologic functions of miR-4472 and its target gene were explored using Transwell, cell proliferation, and flow cytometry assays. Bioinformatics tools, dual-luciferase reporter assays, and Western blot were used to identify the target genes of miR-4472. Western blot was used to explain the participation of miR-4472 and target gene in epithelial-to-mesenchymal transition., Results: miR-4472 was significantly upregulated in highly metastatic breast cancer tissues, and its expression was positively associated with larger tumor size and advanced pTNM stage. miR-4472 promoted breast cancer cell metastasis and growth. Repulsive guidance molecule A (RGMA) was a direct target gene of miR-4472. RGMA was identified as a suppressor in cancer metastasis. miR-4472 downregulated expression of RGMA and promoted epithelial-to-mesenchymal transition by suppressing E-cadherin and initiating vimentin, β-catenin, and Slug., Conclusions: miR-4472 contributes to the progression of breast cancer by regulating RGMA expression and inducing epithelial-to-mesenchymal transition, indicating that miR-4472/RGMA might serve as a therapeutic target for breast cancer., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Diabetic rats display cognition impairments accompanied by activation of NF-κB signalling and increased Aβ expression. Ghrelin has been suggested to improve cognition in diabetic rats. In this study, we investigated the role of ghrelin on cognition and NF-κB mediated Aβ production in diabetic rats. A diabetic rat model was established with streptozotocin (STZ) injection, and diabetic rats were intracerebroventricularly administered with ghrelin or (D-lys3)-GHRP-6 (DG). Our results showed that diabetic rats had cognition impairment in the Morris water maze test, accompanied by the higher expression of Aβ in the hippocampus. Western blot analysis showed that diabetic rats exhibited significantly decreased levels of GHSR-1a and protein phosphatase 1 (PP1) in the hippocampus and increased activation of the IKK/NF-κB/BACE1 pathway. Chronic ghrelin administration upregulated hippocampal PP1 expression, suppressed IKK/NF-κB/BACE1 mediated Aβ production, and improved cognition in STZ-induced diabetic rats. These effects were reversed by DG. Then, primary rat hippocampal neurons were isolated and treated with high glucose, followed by Ghrelin and DG, PP1 or IKK. Similar to the in vivo results, high glucose suppressed the expression levels of GHSR-1a and PP1, activated the IKK/NF-κB/BACE1 pathway, increased Aβ production. Ghrelin suppressed IKK/NF-κB/BACE1 induced Aβ production. This improvement was reversed by DG and a PP1 antagonist and was enhanced by the IKK antagonist. Our findings indicated that chronic ghrelin administration can suppress IKK/NF-κB/BACE1 mediated Aβ production in primary neurons with high glucose treatment and improve the cognition via PP1 upregulation in diabetic rats., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020. Published by Elsevier Inc.)

Breast cancer is the most common female malignancy worldwide, however its molecular pathogenesis still needs in-depth investigation. Here we first revealed that the olfactory receptor family 2, subfamily T, member 6 (OR2T6) was significantly over-expressed in breast cancer tissues compared with normal breast tissues. OR2T6 expression was tightly correlated with higher TNM staging, positive lymph node metastasis, and associated with poorer patients' overall and disease-free survival. And OR2T6 enhanced the proliferation, invasion, and migration ability of breast cancer cell lines in vitro (MCF-7 and MDA-MD-231). Mechanically, it promoted the expression of mesenchymal markers (Vimentin, N-cadherin, and β-catenin) while inhibited E-cadherin expression, suggesting that OR2T6 played a key role in the regulation of epithelial-mesenchymal transition (EMT) process. Moreover, the human gene expression microarray clarified that MAPK/ERK pathway could be initiated by OR2T6 at mRNA level, which was further confirmed at protein level by western blot analysis. Thus, we concluded that OR2T6, as a novel oncogene, contributed to the progression of breast carcinoma by the initiation of EMT and MAPK/ERK pathway., (Copyright © 2019 Li, Wang, Ma, Shi, Wang, Li, He, Wang and Gao.)

Background: Gastric cancer is the second most common cause of cancer-related mortality; thus, the mechanisms underlying tumor metastasis and growth in gastric cancer need to be extensively explored., Methods: Differentially expressed genes were examined in gastric cancer samples with lymph node metastasis (LNM) and without LNM using mRNA microarray and RT-qPCR. The effects of G antigen 7B (GAGE7B) on the metastasis, growth, and angiogenesis of gastric cancer were investigated in vitro and in vivo. GAGE7B protein expression was detected by immunohistochemical (IHC) analysis. Microarray, RT-qPCR, and western blot assays were performed to detect downstream target genes of GAGE7B. Dual-luciferase reporter and western blot assays were used to identify miRNAs that could negatively regulate GAGE7B., Results: GAGE7B was significantly overexpressed in samples with LNM. High expression levels of GAGE7B were associated with advanced clinical stage and poor patient survival. GAGE7B dramatically enhanced the metastasis, growth, and angiogenesis ability of gastric cancer. GAGE7B was further demonstrated to promote the progression of gastric cancer by activating the p38δ/pMAPKAPK2/pHSP27 pathway. However, the GAGE7B-induced p38δ/pMAPKAPK2/pHSP27 pathway was inactivated by miR-30c, as the expression levels of both GAGE7B and p38δ were found to be directly suppressed by miR-30c. Intriguingly, GAGE7B was found to be a ceRNA for p38δ, as it activated the p38δ/pMAPKAPK2/pHSP27 pathway by competitively binding miR-30c., Conclusions: GAGE7B may serve as a prognostic indicator in gastric cancer. GAGE7B significantly promotes gastric cancer progression by upregulating the p38δ/pMAPKAPK2/pHSP27 pathway, but it is negatively regulated by miR-30c. GAGE7B and miR-30c may be potential therapeutic targets in gastric cancer.

Previously published equations to estimate glomerular filtration rate (GFR) have limited accuracy in Asian populations. We aimed to develop and validate a more accurate equation for estimated GFR (eGFR) in the Chinese population, using data from 8571 adults who were referred for direct measurement of GFR by renal dynamic imaging (mGFR) at 3 representative hospitals in China. Patients from the Third Xiangya Hospital were included in our development (n=1730) and internal validation sets (n=1042) and patients from the other hospitals comprised the external validation set (n=5799). We excluded patients who were prescribed medications known to influence the tubular secretion of creatinine, patients on dialysis, kidney transplant recipients, and patients with missing creatinine values or with creatinine >700 μmol/l. We derived a novel eGFR equation by linear regression analysis and compared the performance to 12 creatinine-based eGFR equations, including previously published equations for use in Chinese or Asian populations. In the development and internal validation sets, the novel Xiangya equation had high accuracy (accuracy within 30% [P30], 79.21% and 84.33%, respectively), low bias (mean difference between mGFR and eGFR, -1.97 and -1.85 ml/min per 1.73 m 2 , respectively), and high precision (interquartile range of the differences, 21.13 and 18.88 ml/min per 1.73 m 2 , respectively). In external validation, the Xiangya equation had the highest P30 among all eGFR equations, with P30 ≤ 75% for the other 12 equations. This novel equation provides more accurate GFR estimates in Chinese adults and could replace existing eGFR equations for use in the Chinese population., (Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

The γ-aminobutyric acid type A (GABA A ) receptor is an important pentameric inhibitory neurotransmitter receptor, and the γ2 subunit of this receptor plays a key role in potentiation of the GABA A response. We previously detected that the expression of GABA A receptor in the livers of Carassius auratus gibelio significantly increased after medication (avermectin and difloxacin treatment). In order to better understand the mechanism of action of the GABA A receptor γ2 subunit in the livers of C. auratus gibelio, we constructed a C. auratus gibelio liver cDNA library (the titer value of 1.2 × 10 6  cfu/mL) and identified the proteins that interact with the GABA A receptor γ2 subunit by using a yeast two-hybrid assay. The yeast two-hybrid screening yielded seven positive clones, namely, prelid3b, cdc42, sgk1, spg21, proteasome, chia.5, and AP-3 complex subunit beta-1, all of which have been annotated by the NCBI database. The functions of these proteins are complex; therefore, additional studies are required to determine the specific interactions of these proteins with the GABA A receptor γ2 subunit in the liver of C. auratus gibelio. Although the interactions identified by the yeast two-hybrid system should be considered as preliminary results, the findings of this study may provide further direction and a foundation for future research focusing on the mechanisms of the GABA A receptor γ2 subunit in C. auratus gibelio livers.

Background: No risk model for predicting thrombocytopenia associated with periprocedural tirofiban exposure is available. The purpose of this study was to develop a simple clinical pre-procedure risk model based on pre-procedural characteristics for early prediction of thrombocytopenia before patients were exposed to tirofiban. Methods: The series included 1862 patients who underwent percutaneous coronary intervention with tirofiban exposure. Baseline demographic and clinical characteristics were collected from the hospital information system on admission. The earliest pro-procedural platelets within 72 h were used to evaluate the thrombocytopenia incidence. Risk factors associated with thrombocytopenia in patients with tirofiban exposure were investigated by univariable and multivariable analyses. Locally weighted scatterplot smoothing procedure was used to identify the cut points for the numeric variables. The discriminatory power of the scoring system was assessed with the receiver operating characteristic (ROC) curve analysis. Results: The occurrence of thrombocytopenia was 4.02% (75 of 1862), 4.01% (56 of 1396), and 4.08% (19 of 466) in the overall, developmental, and validation data sets, respectively. The risk score was developed based on five independent predictors: age ≥65y, white blood cell ≥12 × 10 9 /L, diabetes mellitus, congestive heart failure, and chronic kidney disease. This tool was well calibrated (Hosmer Lemeshow χ 2 = 6.914; P = 0.546) and good discrimination was well obtained in validation data set (C-statistic, 0.82). Conclusion: The clinical pre-procedure risk model is a simple and accurate tool for early identification of high-risk patients of thrombocytopenia before tirofiban exposure, allowing for timely and appropriate intervention.

Purpose: Numerous studies have been conducted on the population pharmacokinetics of tacrolimus in adult renal transplant recipients. It has been reported that the cytochrome P450 (CYP) 3A5 genotype is an important cause of variability in tacrolimus pharmacokinetics. However, the predictive performance of population pharmacokinetic (PK) models of tacrolimus should be evaluated prior to their implementation in clinical practice. The aim of the study reported here was to test the predictive performance of these published PK models of tacrolimus., Methods: A literature search of the PubMed and Web of Science databases ultimately led to the inclusion of eight one-compartment models in our analysis. We collected a total of 1715 trough concentrations from 174 patients. Predictive performance was assessed based on visual and numerical comparison bias and imprecision and by the use of simulation-based diagnostics and Bayesian forecasting., Results: Of the eight one-compartment models assessed, seven showed better predictive performance in CYP3A5 extensive metabolizers in terms of bias and imprecision. Results of the simulation-based diagnostics also supported the findings. The model based on a Chinese population in 2013 (model 3) showed the best and most stable predictive performance in all the tests and was more informative in CYP3A5 extensive metabolizers. As expected, Bayesian forecasting improved model predictability. Diversity among models and between different CYP3A5 genotypes of the same model was also narrowed by Bayesian forecasting., Conclusions: Based on our results, we recommend using model 3 in CYP3A5 extensive metabolizers in clinical practice. All models had a poor predictive performance in CYP3A5 poor metabolizers, and they should be used with caution in this patient population. However, Bayesian forecasting improved the predictability and reduced differences, and thus the models could be applied in this latter patient population for the design of maintenance dose.

Long noncoding RNAs (lncRNA) are dysregulated in various human cancers and control tumor development and progression. However, the upstream mechanisms underlying their dysregulation remain unclear. Here, we demonstrate that the expression of hepatocyte nuclear factor 1 homeobox A antisense RNA 1 (HNF1A-AS1) is significantly upregulated in gastric cancer tissues. Overexpression of HNF1A-AS1 enhanced cell proliferation and promoted cell-cycle progression, whereas knockdown of HNF1A-AS1 elicited the opposite effects. Early growth response protein 1 (EGR1) directly bound the HNF1A-AS1 promoter region and activated its transcription. Overexpression of EGR1 enhanced cell proliferation and promoted cell-cycle promotion, similar to the function of HNF1A-AS1. HNF1A-AS1 functioned as competing endogenous RNA (ceRNA) by binding to miR-661, upregulating the expression of cell division cycle 34 (CDC34), which is a direct target of miR-661. EGR1 and HNF1A-AS1 enhanced the expression of cyclin-dependent kinase 2 (CDK2), CDK4, and cyclin E1 but inhibited the expression of p21 by promoting CDC34-mediated ubiquitination and degradation of p21. Taken together, these findings suggest that EGR1-activated HNF1A-AS1 regulates various pro- and antigrowth factors to promote the development of gastric cancer, implicating it as a possible target for therapeutic intervention in this disease. Significance: This study provides novel insights into mechanisms by which the noncoding RNA HNF1A-AS1 contributes to gastric cancer progression through modulation of the cell cycle. Cancer Res; 78(20); 5877-90. ©2018 AACR ., (©2018 American Association for Cancer Research.)

Serum cystatin C (CysC) measurement is regarded as a simple and practical alternative to measure residual renal function for dialysis patients. Recent studies have shown that CysC has better diagnostic accuracy or at least equivalence to creatinine in predicting the early stages of renal damage, and is closely related to clinical outcomes of dialysis patients. Thus, the applicability of CysC-derived equations in patients undergoing dialysis should be paid attention. Here, we review the role of CysC in diagnosis, renal function evaluation, and prognosis outcomes for dialysis patients, so as to provide them with useful suggestions on evaluating renal function and predicting adverse outcomes in clinical practice., (Copyright © 2018. Published by Elsevier B.V.)

To examine the relationship of morphological characters of sagittal otolith and the age of Liza haematocheila in the Yangtze Estuary, we analyzed the morphological parameters of 324 pairs of otoliths extracted from 358 L. haematocheila specimens from the Yangtze Estuary in February to June of 2017. The results showed that sagittal otolith had rostrum, antirostrum and obvious central notch. The size and shape of sagittal otolith significantly changed with their growth, from regular melon seeds shape outline to long narrow leaf shape and increasing irregular wavy outline. The average density of sagittal otolith was 1.52 mg·mm -2 . The average rectangularity was 0.68. The length of sagittal otolith was 0.021%-0.047% of entire body length (BL), the width was 0.009%-0.021% of entire BL, and the mass was 0.045‰-0.731‰ of the entire body mass (BM). Otolith length (OL), otolith width (OW) and otolith mass (OM) were all significantly related to the BL, with the determination coefficient for OW and OM model being the highest (R 2 =0.928). The relationship between OM and BL was described best by exponential regression: OM=0.0009BL 1.8737 (R 2 =0.967). The relationships between OM and age (A), BL and A were well fitted by multinomial regressions, respectively: OM=2.9262A 2 +4.8437A+2.1894 (R 2 =0.847), BL=-3.2248A 2 +102.54A+38.373 (R 2 =0.858). In addition, OM was linearly correlated with A. The estimated otolith's ages from the model did not significantly variate from the real ages counting from annulus counts. Therefore, OM could be an effective parameter for the age estimation of L. haematocheila.

Background and Objectives: Diltiazem is a benzothiazepine calcium blocker and widely used in renal transplant patients since it improves the level of tacrolimus or cyclosporine A concentration. Several population pharmacokinetic (PopPK) models had been established for cyclosporine A and tacrolimus but no specific PopPK model was established for diltiazem. The aim of the study is to develop a PopPK model for diltiazem in renal transplant recipients and provide relevant pharmacokinetic parameters of diltiazem for further pharmacokinetic interaction study., Methods: Patients received tacrolimus as primary immunosuppressant agent after renal transplant and started administration of diltiazem 90 mg twice daily on 5th day. The concentration of diltiazem at 0, 0.5, 1, 2, 8, and 12 h was measured by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Genotyping for CYP3A4*1G, CYP3A5*3, and MDR1 3435 was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). 25 covariates were considered in the stepwise covariate model (SCM) building procedure., Results: One-compartment structural pharmacokinetic model with first-order absorption and elimination was used to describe the pharmacokinetic characteristics of diltiazem. Total bilirubin (TBIL) influenced apparent volume of distribution (V/F) of diltiazem in the forward selection. The absorption rate constant (K a ), V/F, and apparent oral clearance (CL/F) of the final population pharmacokinetic (PopPK) model of diltiazem were 1.96/h, 3550 L, and 92.4 L/h, respectively., Conclusion: A PopPK model of diltiazem is established in Chinese renal transplant recipients and it will provide relevant pharmacokinetic parameters of diltiazem for further pharmacokinetic interaction study.

Tumor metastasis is the main reason of cancer-related death for gastric cancer (GC) patients and gene expression microarray data indicate that kinesin family member 26B (KIF26B) is one of the most upregulated genes in metastatic GC samples. Specifically, KIF26B expression was upregulated in a stepwise manner from non-tumorous gastric mucosa, primary GC tissues without metastasis, via primary GC tissues with metastasis, to secondary lymph node metastatic (LNM) foci. Increased expression of KIF26B was correlated with tumor size, positive LNM or distant metastases and poor prognosis. KIF26B, negatively regulated by miR-372, promoted GC cell proliferation and metastasis in vitro and in vivo. Mechanistic investigations confirmed that the main target of KIF26B was the vascular endothelial growth factor (VEGF) signaling pathway, particularly by inhibition or overexpression of VEGFA, PXN, FAK, PIK3CA, BCL2 and CREB1. Thus, KIF26B, a novel oncogene regulated by miR-372, promotes proliferation and metastasis through the VEGF pathway in GC.

Chemoresistance represents a major obstacle to effective therapy for breast cancer. Emerging evidences associated aberrantly expressed miRNAs with tumor development and chemoresistance. MiR-1268b has never been studied in any cancers before, and its roles in mediating tumor progression and drug resistance are still unclear. Selected from miRNA microarray and confirmed by real-time quantitative PCR (RT-qPCR), miR-1268b was found to be significantly upregulated in drug sensitive and ERBB2 negative tissues, as well as in breast cancer patients with low clinical stage. And miR-1268b had a higher expression in chemosensitive breast cancer cell lines, compared with the chemoresistant cell line. Moreover, the results revealed that miR-1268b induced breast cancer cell apoptosis and increased cell chemosensitivity. ERBB2 was demonstrated to be the target gene of miR-1268b by dual-luciferase reporter assays, western blot, and immunocytochemistry. Furthermore, PI3KCA, AKT, BCL2 in the ERBB2-PI3K-AKT signaling pathway were found to be downstream effectors of miR-1268b. In conclusion, miR-1268b increased chemosensitivity, at least in part, via modulation of PI3K-AKT pathway by targeting ERBB2. MiR-1268b may serve as a potential therapeutic target for patients with breast cancers., Competing Interests: CONFLICTS OF INTEREST All authors declare that there are no conflicts of interest.

Diabetes mellitus (DM) has been regarded as an important risk factor for Alzheimer's disease (AD), and diabetic patients and animals have shown cognitive dysfunction. More research has shown that the amyloid-β (Aβ), which is a hallmark of AD, was found deposited in the hippocampus of diabetic rats. This Aβ accumulation is regulated by the receptor for advanced glycation end products (RAGE) and low-density lipoprotein receptor-related protein (LRP-1). However, the expression of RAGE and LRP-1 in diabetic rats is not very clear. In the present study, we used streptozotocin (STZ)-induced diabetic rats to investigate whether the expression of RAGE and LRP-1 is related to Aβ 1-42 deposition at the hippocampus, prefrontal lobe, and amygdala in DM. We found that diabetic rats had longer escape latency and less frequency of entrance into the target zone than that of the control group (P < 0.05) in the Morris water maze (MWM) test. The Aβ 1-42 expression in the hippocampus and prefrontal lobe significantly increased in the DM group compared to the control group (P < 0.05). RAGE increased (P < 0.05), while LRP-1 decreased (P < 0.05) in the hippocampus tissue and prefrontal lobe tissue of DM rats. The Aβ 1-42 deposition was correlated with RAGE positively (P < 0.05), but with LRP-1 negatively (P < 0.05). Further, the expression levels of Aβ 1-42 , RAGE, and LRP-1 were not changed in the amygdala between the diabetic rats and the control group. These findings indicated that upregulating RAGE and/or downregulating LRP-1 at the hippocampus and the prefrontal lobe contributed to the Aβ 1-42 accumulation and then further promoted the cognitive impairment of diabetic rats.