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Mian-Hong Zheng,1,* Fahime Bigdeli,2,* Lan-Xing Gao,1,* Deng-Ze Wu,1 Xiao-Wei Yan,3 Mao-Lin Hu,3 Ali Morsali2 1College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035, People’s Republic of China; 2Department of Chemistry, Faculty of Sciences, Tarbiat Modares University, Tehran, Iran; 3College of Materials and Chemical Engineering, and Guangxi Key Laboratory of Calcium Carbonate Resources Comprehensive Utilization, Hezhou University, Hezhou, Guangxi 542800, People’s Republic of China*These authors contributed equally to this workCorrespondence: Deng-Ze Wu; Ali Morsali Email wudengze@wzu.edu.cn; morsali_a@modares.ac.irAim: A new Ag(I) complex (A3) was synthesized and evaluated for its anticancer activity against human cancer cell lines.Materials and Methods: The complex A3 was characterized by 1H, 13C, and 31P nuclear magnetic resonance (NMR), infrared (IR) spectra, elemental analysis, and X-ray crystallography. The interaction of the complex with CT-DNA was studied by electronic absorption spectra, fluorescence spectroscopy, and cyclic voltammetry; cell viability (%) was assessed by absorbance measurement of the samples.Results: The interaction mode of the complex A3 with DNA is electrostatic, and this complex shows good potential in anticancer properties against HCT 116 (human colorectal cancer cells) and MDA-MB-231 (MD Anderson-metastatic breast) cell lines with 0.5 micromolar concentrations.Conclusion: The Ag(I) complex could interact with DNA noncovalently and has anticancer properties.Keywords: binuclear Ag(I) complex, X-ray crystallography, DNA, electrostatic binding, anticancer

Background: Emotional reactions, such as anxiety, irritability, and aggressive behavior, have attracted clinical attention as behavioral and emotional problems in preschool-age children., Aim: To investigate the current status of family rearing, parental stress, and behavioral and emotional problems of preschool children and to analyze the mediating effect of the current status of family rearing on parental stress and behavioral/emotional problems., Methods: We use convenience sampling to select 258 preschool children in the physical examination center of our hospital from October 2021 to September 2023. The children and their parents were evaluated using a questionnaire survey. Pearson's correlation was used to analyze the correlation between child behavioral and emotional problems and parental stress and family rearing, and the structural equation model was constructed to test the mediating effect., Results: The score for behavioral/emotional problems of 258 preschool children was (27.54 ± 3.63), the score for parental stress was (87.64 ± 11.34), and the score for parental family rearing was (31.54 ± 5.24). There was a positive correlation between the behavioral and emotional problems of the children and the "hostile/mandatory" parenting style; meanwhile, showed a negative correlation with the "support/ participation" parenting style (all P < 0.05). The intermediary effect value between the family upbringing of parents in parental stress and children's behavior problems was 29.89%., Conclusion: Parental family upbringing has a mediating effect between parental stress and behavioral and emotional problems of children. Despite paying attention to the behavioral and emotional problems of preschool-age children, clinical medical staff should provide correct and reasonable parenting advice to their parents to promote the mental health of preschool-age children., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.)

Ophthalmology is a subject that highly depends on imaging examination. Artificial intelligence (AI) technology has great potential in medical imaging analysis, including image diagnosis, classification, grading, guiding treatment and evaluating prognosis. The combination of the two can realize mass screening of grass-roots eye health, making it possible to seek medical treatment in the mode of "first treatment at the grass-roots level, two-way referral, emergency and slow treatment, and linkage between the upper and lower levels". On the basis of summarizing the AI technology carried out by scholars and their teams all over the world in the field of ophthalmology, quite a lot of studies have confirmed that machine learning can assist in diagnosis, grading, providing optimal treatment plans and evaluating prognosis in corneal and conjunctival diseases, ametropia, lens diseases, glaucoma, iris diseases, etc . This paper systematically shows the application and progress of AI technology in common anterior segment ocular diseases, the current limitations, and prospects for the future., Competing Interests: Conflicts of Interest: Liu YH, None; Li LY, None; Liu SJ, None; Gao LX, None; Tang Y, None; Li ZH, None; Ye Z, None., (International Journal of Ophthalmology Press.)

Kmeria septentrionalis is a critically endangered tree endemic to Guangxi, China, and is listed on the International Union for Conservation of Nature's Red List. The lack of genetic information and high-quality genome data has hindered conservation efforts and studies on this species. In this study, we present a chromosome-level genome assembly of K. septentrionalis. The genome was initially assembled to be 2.57 Gb, with a contig N50 of 11.93 Mb. Hi-C guided genome assembly allowed us to anchor 98.83% of the total length of the initial contigs onto 19 pseudochromosomes, resulting in a scaffold N50 of 135.08 Mb. The final chromosome-level genome, spaning 2.54 Gb, achieved a BUSCO completeness of 98.9% and contained 1.67 Gb repetitive elements and 35,927 coding genes. This high-quality genome assembly provides a valuable resource for understanding the genetic basis of conservation-related traits and biological properties of this endangered tree species. Furthermore, it lays a critical foundation for evolutionary studies within the Magnoliaceae family., (© 2024. The Author(s).)

The isatin group is widespread in nature and is considered to be a privileged building block for drug discovery. In order to develop novel SHP1 inhibitors with fluorescent properties as tools for SHP1 biology research, this work designed and synthesized a series of isatin derivatives. The presentive compound 5a showed good inhibitory activity against SHP1 PTP with IC 50 of 11 ± 3 μM, displayed about 92% inhibitory rate against MV-4-11 cell proliferation at the concentration of 20 μM, exhibited suitable fluorescent properties with a long emission wavelength and a large Stokes shift, and presented blue fluorescent imaging in HeLa cells with low cytotoxicity. This study could offer chemical tool to further understand SHP1 biology and develop novel SHP1 inhibitors in therapy.

Protein tyrosine phosphatase 1B (PTP1B) has proven to be an attractive target for the treatment of cancer, diabetes and other diseases. Although many PTP1B inhibitors with various scaffolds have been developed, there is still a lack of PTP1B inhibitor with high specificity and acceptable pharmacological properties. Therefore, it is urgent to develop more methods to explore complex action mode of PTP1B and ligands for designing ideal PTP1B modulators. In this work, we developed a potential molecular dynamics (MD) analytic mode to analyze the mechanism of active compounds 6a and 6e against PTP1B from different perspectives, including the stable ability, interactions and binding site of ligand and protein, the binding energy, relative movement between residues and changes in protein internal interactions. The simulated results demonstrated that compound 6a bound more stably to the active pocket of PTP1B than 6e due to its smaller molecular volume (326 Å 3 ), matched electronegativity, and enhanced the positive correlation motion of residues, especially for WPD loop and P loop. Lastly, compound 6a as a competitive inhibitor for PTP1B was verified by enzyme kinetic assay. This work successfully studied the mechanism of compound 6a against PTP1B from various aspects, enriched the analysis of interaction mode between PTP1B and inhibitors. In summary, we hope that this work could provide more theoretical information for designing and developing more novel and ideal PTP1B inhibitors in the future., 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 © 2023. Published by Elsevier Inc.)

As a major neuron type in the brain, the excitatory neuron (EN) regulates the lifespan in C. elegans. How the EN acquires senescence, however, is unknown. Here, we show that growth differentiation factor 11 (GDF11) is predominantly expressed in the EN in the adult mouse, marmoset and human brain. In mice, selective knock-out of GDF11 in the post-mitotic EN shapes the brain ageing-related transcriptional profile, induces EN senescence and hyperexcitability, prunes their dendrites, impedes their synaptic input, impairs object recognition memory and shortens the lifespan, establishing a functional link between GDF11, brain ageing and cognition. In vitro GDF11 deletion causes cellular senescence in Neuro-2a cells. Mechanistically, GDF11 deletion induces neuronal senescence via Smad2-induced transcription of the pro-senescence factor p21. This work indicates that endogenous GDF11 acts as a brake on EN senescence and brain ageing., (© 2023. The Author(s).)

Aim: To observe the effect of low oxygen concentration on the neural retina in human induced pluripotent stem cell (hiPSC)-derived retinal organoids (ROs)., Methods: The hiPSC and a three-dimensional culture method were used for the experiments. Generated embryoid bodies (EBs) were randomly and equally divided into hypoxic and normoxic groups. Photographs of the EBs were taken on days 38, 45, and 52, and the corresponding volume of EBs was calculated. Simultaneously, samples were collected at these three timepoints, followed by fixation, sectioning, and immunofluorescence., Results: The proportion of Ki67-positive proliferating cells increased steadily on day 38; this proliferation-promoting effect tended to increase tissue density rather than tissue volume. On days 45 and 52, the two groups had relatively similar ratios of Ki67-positive cells. Further immunofluorescence analysis showed that the ratio of SOX2-positive cells significantly increased within the neural retina on day 52 ( P <0.05). In contrast, the percentage of PAX6- and CHX10-positive cells significantly decreased following hypoxia treatment at all three timepoints ( P <0.01), except for CHX10 at day 45 ( P >0.05). Moreover, the proportion of PAX6 - /TUJ1 + cells within the neural retinas increased considerably ( P <0.01, <0.05, <0.05 respectively)., Conclusion: Low oxygen promotes stemness and proliferation of neural retinas, suggesting that hypoxic conditions can enlarge the retinal progenitor cell pool in hiPSC-derived ROs., (International Journal of Ophthalmology Press.)

Doxorubicin is one of the most widely used antitumor drugs and is currently produced via the chemical conversion method, which suffers from high production costs, complex product separation processes, and serious environmental pollution. Biocatalysis is considered a more efficient and environment-friendly method for drug production. The cytochrome daunorubicin C-14 hydroxylase (DoxA) is the essential enzyme catalyzing the conversion of daunorubicin to doxorubicin. Herein, the DoxA from Streptomyces peucetius subsp. caesius ATCC 27952 was expressed in Escherichia coli , and the rational design strategy was further applied to improve the enzyme activity. Eight amino acid residues were identified as the key sites via molecular docking. Using a constructed screening library, we obtained the mutant DoxA(P88Y) with a more rational protein conformation, and a 56% increase in bioconversion efficiency was achieved by the mutant compared to the wild-type DoxA. Molecular dynamics simulation was applied to understand the relationship between the enzyme's structural property and its substrate-binding efficiency. It was demonstrated that the mutant DoxA(P88Y) formed a new hydrophobic interaction with the substrate daunorubicin, which might have enhanced the binding stability and thus improved the catalytic activity. Our work lays a foundation for further exploration of DoxA and facilitates the industrial process of bio-production of doxorubicin.

Drug resistance is an important factor for treatment failure of gastric cancer. N 6 -methyladenosine (m 6 A) is the predominant mRNA internal modification in eukaryotes. The roles of m 6 A modification in drug resistance of gastric cancer remains unclear. In the present study, the m 6 A methylated RNA level was significantly decreased while the expression of m 6 A demethylase fat mass and obesity-associated protein (FTO) was obviously elevated in cisplatin-resistant (SGC-7901/DDP) gastric cancer cells. Knockdown of FTO reversed cisplatin resistance of SGC-7901/DDP cells both in vitro and in vivo, which was attributed to the inhibition of Unc-51-like kinase 1 (ULK1)-mediated autophagy. Mechanistically, ULK1 expression was regulated in an FTO-m 6 A-dependent and YTHDF2-mediated manner. Collectively, our findings indicate that the FTO/ULK1 axis exerts crucial roles in cisplatin resistance of gastric cancer., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Aim: To quantitatively evaluate the risk of anxiety and depression in patients with uveitis via performing a Meta-analysis., Methods: Three electronic database (PubMed, Embase, and Cochrane Library databases) were searched for studies recording data about uveitis and anxiety as well as depression simultaneously up to January 2021. The incidence rate and standard mean difference (SMD) with a 95% confidence interval (95%CI) were calculated to analyse the association using random-effects models based on heterogeneity tests., Results: In total, 12 observational studies containing 874 patients with uveitis were included. The results showed that there was a significant association between uveitis and anxiety (SMD=0.97, 95%CI: 0.39 to 1.54, P =0.0009) and depression (SMD=0.79, 95%CI: 0.51 to 1.07, P <0.00001). The overall morbidities of anxiety and depression in patients with uveitis were 39% and 17%, respectively. With subgroup analysis, the heterogeneity actually came from different kinds of uveitis. Specifically, the incidence rates of both anxiety and depression were relatively low in patients with anterior uveitis (33% and 15%), moderate in patients with infectious uveitis (46% and 22%), and high in patients with unspecified uveitis (59% and 35%)., Conclusion: It is preliminarily indicated that patients with uveitis may have a high risk of anxiety and depression. Ophthalmologists and psychologists should pay more attention to the psychological state when dealing with patients with uveitis. Further high-quality studies with detailed direct data are needed to draw more precise conclusions., (International Journal of Ophthalmology Press.)

Arsenicals have been widely used in the treatment of cancers such as leukemia and other tumors. However, their side effects limit their clinical application. Stiripentol, a second-line adjunctive treatment for epilepsy with a good safety profile, inhibits microsomal cytochrome-P450-family enzymes to extend the retention time of co-administration. Inspired by the metabolism of stiripentol, the 1,3-benzodioxole responsible for the inhibition and its metabolic derivatives were conjugated with arsenical precursors. The fabricated arsenicals were eliminated much slower in mice and maintained an efficient concentration in the blood for a longer time than that of the arsenical precursors. They also performed better in anti-proliferation by inhibiting the thioredoxin system to induce oxidative stress, and concomitantly to initiate apoptosis in vitro and in vivo. The fabricated arsenicals reversed the hemogram of tumor-bearing mice to normal and eliminated the tumor without causing damage to any organs, exhibiting a good design strategy and pre-clinical application for leukemia and other tumors.

In this paper, a qualitative study was conducted on Jennifer, an EFL teaching professional at the tertiary level in a Chinese context, to investigate her cognitions regarding her professional development and accompanying facilitating factors in her journey from a novice teacher to a teacher leader with Borg's model of language teacher cognition as the conceptual basis for subsequent analysis. Jennifer's written overview and verbal narration in interviews of her journey in professional development were gathered following guiding protocols. Collected data were processed with thematic analysis in NVivo 12. Findings suggest that Jennifer has clear cognitions about how she learned and improved, i.e., the positive changes, in her professional journey and the facilitating factors that mediated her improvement and progress. These facilitating factors were found to include her teaching experience, in-service training, administrative promotion, drawing wisdom from reading Chinese classics, and constant reflection upon her English as a foreign language (EFL) teaching, etc. The implications of the present study for language teacher cognition researchers, English language teacher educators, and EFL teachers in the Chinese context were also discussed., 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 © 2022 Gao and Yang.)

The COVID-19 pandemic caused by SARS-CoV-2 is a global burden on human health and economy. The 3-Chymotrypsin-like cysteine protease (3CL pro ) becomes an attractive target for SARS-CoV-2 due to its important role in viral replication. We synthesized a series of 8 H -indeno[1,2- d ]thiazole derivatives and evaluated their biochemical activities against SARS-CoV-2 3CL pro . Among them, the representative compound 7a displayed inhibitory activity with an IC 50 of 1.28 ± 0.17 μM against SARS-CoV-2 3CL pro . Molecular docking of 7a against 3CL pro was performed and the binding mode was rationalized. These preliminary results provide a unique prototype for the development of novel inhibitors against SARS-CoV-2 3CL pro .

Primary Sjogren's syndrome (pSS) is a complex systemic autoimmune disease, which is difficult to accurately diagnose due to symptom diversity in patients, especially at earlier stages. We tried to find potential single nucleotide polymorphisms (SNPs), copy number variations (CNVs) and related signaling pathways. Genomic DNA was extracted from peripheral blood of 12 individuals (7 individuals from 3 pSS pedigrees and 5 sporadic cases) for whole-exome sequencing (WES) analysis. SNPs and CNVs were identified, followed by functional annotation of genes with SNPs and CNVs. Gene expression profile (involving 64 normal controls and 166 cases) was downloaded from the Gene Expression Omnibus database (GEO) dataset for differentially expression analysis. Sanger sequencing and in vitro validation was used to validate the identified SNPs and differentially expressed genes, respectively. A total of 5 SNPs were identified in both pedigrees and sporadic cases, such as FES, PPM1J, and TRAPPC9. A total of 3402 and 19 CNVs were identified in pedigrees and sporadic cases, respectively. Fifty-one differentially expressed genes were associated with immunity, such as BATF3, LAP3, BATF2, PARP9, and IL15RA. AMPK signaling pathway and cell adhesion molecules (CAMs) were the most significantly enriched signaling pathways of identified SNPs. Identified CNVs were associated with systemic lupus erythematosus, mineral absorption, and HTLV-I infection. IL2-STAT5 signaling, interferon-gamma response, and interferon-alpha response were significantly enriched immune related signaling pathways of identified differentially expressed genes. In conclusion, our study found some potential SNPs, CNVs, and related signaling pathways, which could be useful in understanding the pathological mechanism of pSS.

The Src homology-2 domain containing-protein tyrosine phosphatase-2 (SHP2) is a convergent node for oncogenic cell-signaling cascades including the PD-L1/PD-1 pathway. As an oncoprotein as well as a potential immunomodulator, SHP2 has now emerged as an attractive target for novel anti-cancer agents. Although significant progress has been made in identifying chemotypes of SHP2 inhibitors, these specific compounds might not be clinically useful to inhibit frequently encountered mutated SHP2 variants. Consequently, it is highly desirable to develop chemically different SHP2 inhibitors sensitive to SHP2 mutants. This work developed a new type of SHP2 inhibitors with 2,5-diaryl-1,3,4-oxadiazole scaffold. The representative compound 6l exhibited SHP2 inhibitory activity with IC 50 of 2.73 ± 0.20 µM, showed about 1.56-fold, 5.26-fold, and 7.36-fold selectivity for SHP2 over SHP1, PTP1B and TCPTP respectively. Further investigations confirmed that 6l behaved as mixed-type inhibitor sensitive to leukemia cell TF-1 and inhibited SHP2 mediated cell signaling and proliferation. Molecular dynamics simulation provided more detailed information on the binding modes of compounds and SHP2 protein. These preliminary results could provide a possible opportunity for the development of novel SHP2 inhibitors sensitive to SHP2 mutants with optimal potency and improved pharmacological properties., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Mitochondria, as the powerhouse of most cells, are not only responsible for the generation of adenosine triphosphate (ATP) but also play a decisive role in the regulation of apoptotic cell death, especially of cancer cells. Safe potential delivery systems which can achieve organelle-targeted therapy are urgently required. In this study, for effective pancreatic cancer therapy, a novel mitochondria-targeted and ROS-triggered drug delivery nanoplatform was developed from the TPP-TK-CPI-613 ( TTCI ) prodrug, in which the ROS-cleave thioketal functions as a linker connecting mitochondrial targeting ligand TPP and anti-mitochondrial metabolism agent CPI-613. DSPE-PEG2000 was added as an assistant component to increase accumulation in the tumor via the EPR effect. This new nanoplatform showed effective mitochondrial targeting, ROS-cleaving capability, and robust therapeutic performances. With active mitochondrial targeting, the formulated nanoparticles ( TTCI NPs) demonstrate much higher accumulation in mitochondria, facilitating the targeted delivery of CPI-613 to its acting site. The results of in vitro antitumor activity and cell apoptosis revealed that the IC 50 values of TTCI NPs in three types of pancreatic cancer cells were around 20~30 µM, which was far lower than those of CPI-613 (200 µM); 50 µM TTCI NPs showed an increase in apoptosis of up to 97.3% in BxPC3 cells. Therefore, this mitochondria-targeted prodrug nanoparticle platform provides a potential strategy for developing safe, targeting and efficient drug delivery systems for pancreatic cancer therapy.

Background: Demethylzeylasteral (T-96) is a pharmacologically active triterpenoid monomer extracted from Tripterygium wilfordii Hook F (TWHF) that has been reported to exhibit anti-neoplastic effects against several types of cancer cells. However, the potential anti-tumour effects of T-96 against human Prostate cancer (CaP) cells and the possible underlying mechanisms have not been well studied., Results: In the current study, T-96 exerted significant cytotoxicity to CaP cells in vitro and induced cell cycle arrest at S-phase in a dose-dependent manner. Mechanistically, T-96 promoted the initiation of autophagy but inhibited autophagic flux by inducing ROS-mediated endoplasmic reticulum (ER) stress which subsequently activated the extrinsic apoptosis pathway in CaP cells. These findings implied that T-96-induced ER stress activated the caspase-dependent apoptosis pathway to inhibit proliferation of CaP cells. Moreover, we observed that T-96 enhances the sensitivity of CaP cells to the chemotherapeutic drug, cisplatin., Conclusions: Taken together, our data demonstrated that T-96 is a novel modulator of ER stress and autophagy, and has potential therapeutic applications against CaP in the clinic., (© 2021. The Author(s).)

A facile and efficient route to synthesize N-heterocyclic fused tryptamine-piperazine-2,5-dione conjugates was developed via a post-Ugi cascade reaction. The targeted compounds were prepared by means of a mild reaction and simple operation procedure, which could be applied to a broad scope of starting materials. Compound 6h was demonstrated to induce significant growth inhibition of AsPC-1 and SW1990 human pancreatic cancer cell lines (IC 50 = 6 ± 0.85 μM). Our protocol allows for the construction of a structurally diverse compound library and paves a new avenue for the discovery of pancreatic cancer drug candidates., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)

Tumor development and progression are closely associated with various microRNAs (miRNAs/miRs). We have previously shown that Newcastle disease virus (NDV) strain 7793 induces oncolysis in lung cancer. However, how NDV exerts its oncolytic effect on lung cancer remains to be investigated. The present study assessed the role of miR-204 in the NDV-induced oncolysis of lung cancer A549 cells by oncolysis induction in vitro . miR-204 was significantly upregulated in NDV-treated A549 cells. Overexpression or inhibition of miR-204 was significantly associated with NDV-induced oncolysis in A549 cells. Caspase-3 and Bax, major regulators of the apoptosis pathway, were regulated by miR-204, and the association between caspase-3-related apoptosis and miR-204 was identified in NDV-mediated oncolysis. These data demonstrated that miR-204 as a tumor suppressor played a role in NDV-induced oncolysis in lung cancer cells. The present study demonstrates the potential of strategies using miRs to improve oncolytic NDV potency, and highlights miR-204 as a tumor suppressor in NDV-induced oncolysis of lung cancer cells., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Liang et al.)

A series of 2-ethoxycarbonylthieno[2,3- b ]quinolines were synthesized in the bio-derived "green" solvent γ-valerolactone (GVL) and evaluated for their inhibitory activities against PTP1B, the representative compound 6a displayed an IC 50 value of 8.04 ± 0.71 μM with 4.34-fold preference over TCPTP. These results provided novel lead compounds for the design of inhibitors of PTP1B as well as other PTPs., Competing Interests: The authors have declared no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Despite being one of the most studied proteins in biology, the photolysis mechanism of myoglobin heme affected by endogenous substances free amino acids is still in controversy. The transient absorption and kinetic processes of photo-excited myoglobin in three forms and the effects of free excited tryptophan on redox reaction of myoglobin were monitored by laser flash photolysis. With dual energy superposition of direct light irradiation and indirect energy transferred from the free excited tryptophan, the variation value in optical density (ΔOD) of MetMb increased by 66.7%, from 0.9 to 1.5. The ΔOD value of MbO 2 in ferrous form increased from 0.9 to 1.25, while the ΔOD value of DeoxyMb increased from 0.75 to 1.2. The decay time of excited DeoxyMb was prolonged obviously with the excited tryptophan, while the decay time of excited MbO 2 and MetMb was shortened significantly. The excited tryptophan could promote laser induced reaction processes of myoglobin in different forms by intermolecular energy transfer to one final similar photo reaction state. The possible photo induced reaction mechanisms of DeoxyMb, MbO 2 , MetMb with and without free tryptophan were also proposed., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The sudden global outbreak of COVID-19 in late 2019 has led to thriving online teaching, including the teaching of languages, across the world. As the online teaching of English-as-a-foreign-language (EFL) in Chinese universities is facing new challenges, EFL teachers have been positively exploring new solutions. To understand how EFL teachers were coping with the challenges, we set up this research as part of a larger study to examine EFL teachers' cognitions about online teaching in response to the disruption of normal teaching plans. We did so by taking a qualitative approach through analyzing in-depth interviews with three EFL teachers from a Chinese university. Through thematic analysis we found that teachers had clear cognitions about features, advantages, and constraints of online EFL teaching and that they acquired information and communication technology (ICT) literacy through understanding students' learning needs, online teaching practice, and the necessity of integrating traditional classroom teaching methods into online delivery. We conclude this study with a discussion on its pedagogical implications for similar contexts or colleagues facing similar challenges in other parts of the world., (Copyright © 2020 Gao and Zhang.)

Radiotherapy is one of the most important cancer treatments, but its response varies greatly among individual patients. Therefore, the prediction of radiosensitivity, identification of potential signature genes, and inference of their regulatory networks are important for clinical and oncological reasons. Here, we proposed a novel multiple genomic fused partial least squares deep regression method to simultaneously analyze multi-genomic data. Using 60 National Cancer Institute cell lines as examples, we aimed to identify signature genes by optimizing the radiosensitivity prediction model and uncovering regulatory relationships. A total of 113 signature genes were selected from more than 20,000 genes. The root mean square error of the model was only 0.0025, which was much lower than previously published results, suggesting that our method can predict radiosensitivity with the highest accuracy. Additionally, our regulatory network analysis identified 24 highly important 'hub' genes. The data analysis workflow we propose provides a unified and computational framework to harness the full potential of large-scale integrated cancer genomic data for integrative signature discovery. Furthermore, the regression model, signature genes, and their regulatory network should provide a reliable quantitative reference for optimizing personalized treatment options, and may aid our understanding of cancer progress mechanisms.

A microscale highly fluorescent Eu metal-organic framework (Eu-MOF) was synthesized with terephthalic acid and 1H-1,2,4-triazole-3,5-diamine by one-pot hydrothermal method. And it was characterized by scanning electron microscope, Fourier transform infrared spectroscopy, powder X-ray diffraction, fluorescence spectroscopy, thermogravimetric analysis, and energy dispersive X-ray mapping. The prepared Eu-MOF has high quantum yield of 30.99%, excellent water dispersibility, good fluorescence stability, and favorable thermal stability. Based on the distinctly different fluorescence responses of different emission, the prepared Eu-MOF was used as dual-mode visual sensor for the sensitive detection of berberine hydrochloride and tetracycline. The limits of detection are 78 nM and 17 nM, respectively. The sensing mechanism was also discussed. Moreover, a filter paper sensor has been designed for sensing tetracycline with a notable fluorescence color change from blue to red. The prepared Eu-MOF is promising to be developed as a multi-mode luminescent sensor for visual detection in biochemical analysis. Graphical abstract Illustration of the synthesis of Eu-MOF and its sensing applications for berberine hydrochloride and tetracycline.

Background: Generation of reactive oxygen species (ROS), triggered by ultraviolet radiation (UVR), is associated with carcinogenesis of the skin. UV irradiation induced superoxide anion (O2 •- ) is the key ROS involved in the cellular damage. The cytoprotective efficacy of an unknown anti-oxidant compound can be evaluated by analyzing the production of O2 •- from treated cells., Methods: In this study, a glass carbon electrode functionalized with nanotube@DNA-Mn3(PO4)2 composite was applied to quantitative determination of generation of highly unstable O2 •- from the melanoma A375 cell line following UVR(UV, UVA and UVB). In addition, the cytoprotective efficacy of anti-oxidant α-tocopherol was evaluated by quantifying the production of O2 •- ., Results: The results showed that, UVR triggers generation of O2 •- in melanoma A375 cells, and α-tocopherol is effective in diminishing the production of O2 •- following UV irradiation. By comparing the conventional cell-survival assays results, we found that our simple and quick electrochemical sensing method can quantify O2 •- generation through the biological activity of an anti-oxidant compound (α-tocopherol)., Conclusion: Our label-free electrochemical quantification method for ROS (O2 •- major) in cells facing UVR stress demonstrates its potential application for high-throughput screening of anti-oxidation compounds., Competing Interests: Not applicable.All the authors mentioned in the author section, agreed to submit this paper for publication in Journal of Biological Engineering, and have no dispute for this submission and publication. None of the authors declare any conflict of interest.The authors declare no any competing interests regarding the submission and publication of this article in Journal of Biological Engineering.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

To investigate the susceptibility of Chukars to duck avian influenza virus H9N2 and explore their role in interspecies transmission of influenza viruses. Chukars were inoculated with duck avian influenza viruses H9N2. The present study demonstrated that inflammatory lesions and virus antigen were present in the trachea, bronchus, and parabronchus, and the viruses could be isolated from throat swabs and lung tissue homogenate supernatants. At 14 d post virus inoculation, anti-H9 influenza virus antibody in the serum was detected. The results indicated that Chukars are susceptible to duck avian influenza virus and serve as an intermediate host, thereby facilitating viral gene evolution and supporting the need for continued surveillance of epidemiology and evolution of the influenza virus in Chukars., (Copyright © 2018 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Two experiments were conducted to determine the effects of viscosity and fermentability of purified nonstarch polysaccharides (NSP) on intestinal nutrient and energy flow and hindgut fermentation in growing pigs. In Exp. 1, 15 ileal-cannulated pigs (50.5 ± 2.9 kg BW) were allotted to 5 diets in a 2-period incompletely randomized design. Pigs were provided a cornstarch N-free diet (CST) or a diet containing 5% inulin (INU), carboxymethylcellulose sodium (CMC), microcrystalline cellulose (MCC), or Solka-Floc (SFC). Apparent ileal digestibility (AID) of DM, ash, and GE were greater ( < 0.05) in the MCC and SFC diets than in the INU and CMC diets. Apparent total tract digestibility (ATTD) of DM, carbohydrates (CHO), and GE and the DE content in the CST and INU diets were greater ( < 0.01) than in the CMC, MCC, and SFC diets. Hindgut disappearance of DM, CHO, and GE in the INU diet was greater ( < 0.05) than in the other N-free diets. The ileal endogenous flow of His, Ile, Leu, Met, Thr, Val, and all dispensable AA in the CMC diet was greater ( < 0.05) than in the other diets. In Exp. 2, 6 ileal-cannulated pigs were allotted to 3 diets containing either a corn-soybean meal control diet or the control diet with 5% INU or CMC in a replicated 3 × 3 Latin square design. Standardized ileal digestibility (SID) of Ala, Arg, Asp, Cys, Gly, His, Ile, Leu, Lys, Phe, Ser, Thr, and Val were greater ( < 0.05) in the CMC diet than in the control and INU diets. Incorporation of 5% INU or CMC in the control diet reduced ( < 0.01) the AID of arabinoxylan and insoluble and total NSP. The ATTD of NSP and cellulose and the hindgut disappearance of NSP, β-glucan, and cellulose in the CMC diet were less ( < 0.01) than in the control and INU diets. Inclusion of 5% INU in the diet increased ( < 0.01) hindgut fermentation of insoluble and total NSP compared with the control and CMC diets. In conclusion, depending on the viscosity and fermentability of the NSP, different sources will have different effects on nutrient digestibility and hindgut fermentation. Addition of 5% INU to a corn-soybean meal diet reduced digestibility of the NSP component in the ileum and increased hindgut fermentation of total NSP. In contrast, the inclusion of CMC increased the AID and SID of the diet and reduced total tract digestion and hindgut fermentation of NSP component. Carboxymethylcellulose sodium is not recommended as a source of synthetic fiber in a N-free diet to determine the SID of AA of diets.

Newcastle disease virus (NDV) is responsible for tumoricidal activity in vitro and in vivo. However, the mechanisms that lead to this activity are unclear. Natural killer cells are able to induce apoptosis of tumor cells through multiple pathways, including the tumor necrosis factor-related apoptosis-inducing ligand-death receptor pathway. We previously showed that exposure of NK and T cells to NDV resulted in enhanced tumoricidal activity that was mediated by upregulated expression of the TRAIL gene, via an interferon gamma -dependent pathway. Other pathways involved in the upregulated expression of TRAIL are yet to be identified. In the current study, we used mice in which the IFN-γ receptor one gene was inactivated functionally. We identified an IFN-γ-independent TRAIL pathway in the NDV-stimulated NK cells. Hemagglutinin-neuramidinase induced expression of the TRAIL gene in IFN-R1-/- NK cells by binding to the NKp46 receptor. This upregulation was inhibited by pretreatment of NDV with a neutralizing monoclonal antibody against HN, or desialylation of NK cells. Phosphorylation of spleen tryosine kinases and IκBα was increased in HN-induced IFN-R1-/- NK cells. Treatment with the HN neutralizing monoclonal antibody, pharmacological disialylation, or a Syk inhibitor decreased Syk and IκBα phosphorylation levels. We concluded that killer activation receptors pathway is involved in the IFN-γ-independent TRAIL expression of NDV-stimulated NK cells, and these are activated by Syk and NF-κB.

Co-trimoxazole, a fixed-dose combination of sulfamethoxazole (SMX) and trimethoprim (TMP), has been used for the treatment of bacterial infections since the 1960s. Since it has long been assumed that the synergistic effects between SMX and TMP are the consequence of targeting 2 different enzymes of bacterial folate biosynthesis, 2 genes ( pabB and nudB ) involved in the folate biosynthesis of Escherichia coli were deleted, and their effects on the susceptibility to antifolates were tested. The results showed that the deletion of nudB resulted in a lag of growth in minimal medium and increased susceptibility to both SMX and TMP. Moreover, deletion of nudB also greatly enhanced the bactericidal effect of TMP. To elucidate the mechanism of how the deletion of nudB affects the bacterial growth and susceptibility to antifolates, 7,8-dihydroneopterin and 7,8-dihydropteroate were supplemented into the growth medium. Although those metabolites could restore bacterial growth, they had no effect on susceptibilities to the antifolates. Reverse mutants of the nudB deletion strain were isolated to further study the mechanism of how the deletion of nudB affects susceptibility to antifolates. Targeted sequencing and subsequent genetic studies revealed that the disruption of the tetrahydromonapterin biosynthesis pathway could reverse the phenotype caused by the nudB deletion. Meanwhile, overexpression of folM could also lead to increased susceptibility to both SMX and TMP. These data suggested that the deletion of nudB resulted in the excess production of tetrahydromonapterin, which then caused the increased susceptibility to antifolates. In addition, we found that the deletion of nudB also resulted in increased susceptibility to both SMX and TMP in Salmonella enterica Since dihydroneopterin triphosphate hydrolase is an important component of bacterial folate biosynthesis and the tetrahydromonapterin biosynthesis pathway also exists in a variety of bacteria, it will be interesting to design new compounds targeting dihydroneopterin triphosphate hydrolase, which may inhibit bacterial growth and simultaneously potentiate the antimicrobial activities of antifolates targeting other components of folate biosynthesis., (Copyright © 2017 American Society for Microbiology.)

The objective of the present study was to investigate the effect of feeding two transgenic corn lines containing the mCry1Ac gene from Bacillus thuringiensis strain (BT-799) and the maroACC gene from Agrobacterium tumefaciens strain (CC-2), respectively, on growth, egg quality and organ health indicators. Expression of the mCry1Ac gene confers resistance to Pyrausta nubilalis and the maroACC gene confers tolerance to herbicides. Healthy hens (n=96 placed in cages; 3 hens/cage) were randomly assigned to one of four corn-soybean meal dietary treatments (8 cages/treatment) formulated with the following corn: non-transgenic near-isoline control corn (control), BT-799 corn, CC-2 corn and commercially available non-transgenic reference corn (reference). The experiment was divided into three 4-week phases (week 1 to 4, week 5 to 8 and week 9 to 12), during which hens were fed mash diets. Performance (BW, feed intake and egg production) and egg quality were determined. Following slaughter at the end of 12 weeks of feeding (n=8/treatment), carcass yield and organ weights (heart, liver, spleen, lung, kidneys, stomach and ovary) were recorded; organs and intestines were sampled for histological analysis. Analysis of serum biochemistry parameters to assess the liver and kidney function were performed. No differences in BW, egg production and production efficiency were observed between hens consuming the control diet and hens consuming the BT-799 or CC-2 diet. Haugh unit measures and egg component weights were similar between the control and test groups. Carcass yield was not affected by the diet treatment. Similar organosomatic indices and serum parameters did not indicate the characteristics of organ dysfunction. All observed values of the BT-799 and CC-2 groups were within the calculated tolerance intervals. This research indicates that the performance, egg quality, organ health and carcass yield of laying hens fed diets containing the BT-799 or CC-2 corn line were similar to that of laying hens fed diets formulated with the non-transgenic near-isoline corn with comparable genetic backgrounds.

Three new C-methylated and isoprenylated chalcone derivatives, dentichalcones A-C (1-3), together with six known compounds (4-9), were isolated from the twigs and leaves of Macaranga denticulata. Their structures were elucidated by spectroscopic analysis, including 1D, 2D NMR, and MS data. The known compounds, (2E)-1-(5,7-dihydroxy-2,2,6-trimethyl-2H-benzopyran-8-yl)-3-(4-methoxyphenyl)-2-propen-1-one (4), (2E)-1-(5,7-dihydroxy-2,2-dimethyl-2H-benzopyran-8-yl)-3-phenyl-2-propen-1-one (5), laxichalcone (6), macarangin (7), bonanniol A (8), and bonannione A (9), showed inhibitory activities against protein tyrosine phosphatase 1B (PTP1B) in vitro. Three new C-methylated and isoprenylated chalcone derivatives, dentichalcones A-C (1-3), together with six known compounds, were isolated from the twigs and leaves of Macaranga denticulata. Some compounds showed inhibitory activities against PTP1B in vitro.

Three unprecedented phloroglucinol-diterpene adducts, chlorabietols A-C (1-3), were isolated from the roots of the rare Chloranthaceae plant Chloranthus oldhamii. They represent a new class of compounds, featuring an abietane-type diterpenoid coupled with different alkenyl phloroglucinol units by forming a 2,3-dihydrofuran ring. Their structures were elucidated by detailed spectroscopic analysis, molecular modeling studies, and electronic circular dichroism calculations. Compounds 1-3 showed inhibitory activity against protein tyrosine phosphatase 1B (PTP1B) with IC50 values of 12.6, 5.3, and 4.9 μM, respectively.

A series of 1H-2,3-dihydroperimidine derivatives was designed, synthesized, and evaluated as a new class of inhibitors of protein tyrosine phosphatase 1B (PTP1B) with IC50 values in the micromolar range. Compounds 46 and 49 showed submicromolar inhibitory activity against PTP1B, and good selectivity (3.48-fold and 2.10-fold respectively) over T-cell protein tyrosine phosphatases (TCPTP). These results have provided novel lead compounds for the design of inhibitors of PTP1B as well as other PTPs.

Objective: To explore the clinical characteristics of primary biliary cirrhosis (PBC) with Sjögren syndrome (SS) so as to seek diagnostic rationales., Methods: Sixty-four PBC patients, 57 SS patients and 93 PBC with SS patients were recruited from Peking Union College Hospital between 2006 and 2009. And their clinical, laboratory and pathological data were analyzed., Results: The patients of PBC with SS (53 ± 10) years were older than those of PBC (50 ± 11) years (P < 0.05) or SS (48 ± 14) years (P < 0.05) ; Comparing PBC with SS and SS, fever was more in SS (P < 0.05) ;compare with PBC, the positive rates of anti-centromere antibody (ACA) (P < 0.05) and anti-SSA antibody (P < 0.05) increased obviously in PBC with SS. Comparing with SS, the positive rate of anti-SSA antibody (P < 0.05) and anti-SSB antibody (P < 0.05) were apparently increased obviously in PBC with SS., Conclusion: PBC with SS is a special subgroup with the characteristic both PBC and SS. But it can not differentiate from PBC or SS, Anti-SSA antibody and ACA are helpful for diagnosis of PBC with SS.

Aim: To establish the frequency and clinical features of connective tissue diseases (CTDs) in a cohort of Chinese patients with primary biliary cirrhosis (PBC)., Methods: Three-hundred and twenty-two Chinese PBC patients were screened for the presence of CTD, and the systemic involvement was assessed. The differences in clinical features and laboratory findings between PBC patients with and without CTD were documented. The diversity of incidence of CTDs in PBC of different countries and areas was discussed. For the comparison of normally distributed data, Student's t test was used, while non-parametric test (Wilcoxon test) for the non-normally distributed data and 2 × 2 χ(2) or Fisher's exact tests for the ratio., Results: One-hundred and fifty (46.6%) PBC patients had one or more CTDs. The most common CTD was Sjögren's syndrome (SS, 121 cases, 36.2%). There were nine cases of systemic sclerosis (SSc, 2.8%), 12 of systemic lupus erythematosus (SLE, 3.7%), nine of rheumatoid arthritis (RA, 2.8%), and 10 of polymyositis (PM, 3.1%) in this cohort. Compared to patients with PBC only, the PBC + SS patients were more likely to have fever and elevated erythrocyte sedimentation rate (ESR), higher serum immunoglobulin G (IgG) levels and more frequent rheumatoid factor (RF) and interstitial lung disease (ILD) incidences; PBC + SSc patients had higher frequency of ILD; PBC + SLE patients had lower white blood cell (WBC) count, hemoglobin (Hb), platelet count, γ-glutamyl transpeptidase and immunoglobulin M levels, but higher frequency of renal involvement; PBC + RA patients had lower Hb, higher serum IgG, alkaline phosphatase, faster ESR and a higher ratio of RF positivity; PBC + PM patients had higher WBC count and a tendency towards myocardial involvement., Conclusion: Besides the common liver manifestation of PBC, systemic involvement and overlaps with other CTDs are not infrequent in Chinese patients. When overlapping with other CTDs, PBC patients manifested some special clinical and laboratory features which may have effect on the prognosis.

Aim: To investigate the immunomodulating activity of astragalosides, the active compounds from a traditional tonic herb Astragalus membranaceus Bge, and to explore the molecular mechanisms underlying the actions, focusing on CD45 protein tyrosine phosphatase (CD45 PTPase), which plays a critical role in T lymphocyte activation., Methods: Primary splenocytes and T cells were prepared from mice. CD45 PTPase activity was assessed using a colorimetric assay. Cell proliferation was measured using a [(3)H]-thymidine incorporation assay. Cytokine proteins and mRNAs were examined with ELISA and RT-PCR, respectively. Activation markers, including CD25 and CD69, were analyzed using flow cytometry. Activation of LCK (Tyr505) was detected using Western blot analysis. Mice were injected with the immunosuppressant cyclophosphamide (CTX, 80 mg/kg), and administered astragaloside II (50 mg/kg)., Results: Astragaloside I, II, III, and IV concentration-dependently increased the CD45-mediated of pNPP/OMFP hydrolysis with the EC50 values ranged from 3.33 to 10.42 μg/mL. Astragaloside II (10 and 30 nmol/L) significantly enhanced the proliferation of primary splenocytes induced by ConA, alloantigen or anti-CD3. Astragaloside II (30 nmol/L) significantly increased IL-2 and IFN-γ secretion, upregulated the mRNA levels of IFN-γ and T-bet in primary splenocytes, and promoted CD25 and CD69 expression on primary CD4(+) T cells upon TCR stimulation. Furthermore, astragaloside II (100 nmol/L) promoted CD45-mediated dephosphorylation of LCK (Tyr505) in primary T cells, which could be blocked by a specific CD45 PTPase inhibitor. In CTX-induced immunosuppressed mice, oral administration of astragaloside II restored the proliferation of splenic T cells and the production of IFN-γ and IL-2. However, astragaloside II had no apparent effects on B cell proliferation., Conclusion: Astragaloside II enhances T cell activation by regulating the activity of CD45 PTPase, which may explain why Astragalus membranaceus Bge is used as a tonic herb in treating immunosuppressive diseases.

Background: Paracrine signaling of the hepatocyte growth factor (HGF) cytokine plays an important role in survival and invasion ability of placental trophoblasts. However, the intracellular factors and biological pathways underlying these responses remain unclear., Methods: This study investigated whether HGF affected the expression of homeobox gene HLX1, which is principally expressed in reproductive tissues and in some immune cells, and evaluated the implications of such in the HGF-induced human trophoblast cell line HTR-8/SVneo., Results: HGF was found to up-regulate both HLX1 mRNA and protein levels. Transient transfection of small interfering RNA (siRNA) targeting HLX1 abrogated its induction by HGF. Functionally, HLX1 siRNA not only reduced the growth and invasion capacities of HTR-8/SVneo cells at the basal level, but also inhibited these responses induced by HGF treatment., Conclusions: HLX1 is an essential downstream signaling component of HGF that leads to growth and invasiveness of trophoblast cells.

In 1987, Carney et al described a rare thyroid tumor termed hyalinizing trabecular adenoma presenting characteristics consisting of a trabecular growth pattern and hyalinizing stroma. In subsequent reports, the observed nuclear features and RET alterations led this tumor to be linked to papillary carcinoma. Subsequent reports concerning hyalinizing trabecular carcinoma further complicated its classification. To avoid uncertainties, the definition of hyalinizing trabecular tumor (HTT) is more widely used. Herein, a case of HTT is reported in detail, and the circumstances are also discussed. HTT is thought to be particularly differentiated from papillary carcinoma despite the identical high frequency of nuclear grooves and cytoplasmic inclusions, and MIB-1-positive staining is one of the most accurate diagnostic methods due to the distinct membrane-positive pattern noted in HTT. It is believed that most HTTs are benign and lobectomy is the standard treatment. Pathologists should offer surgeons information concerning diagnosis overlapping with effective treatment.

We report a 32-year-old Outer Mongolian man, with plasmablastic lymphoma (PBL) primarily occured in the central nervous system and diagnosed by surgical resection. This patient appeared headache and magnetic resonance imaging (MRI) showed multiple lesions in the right cerebral hemisphere including the right frontal-parietal lobe and right basal ganglia and the left cerebellum, he was diagnosed as lymphoma by stereotactic biopsy in January 2009 in local hospital, and was given radiotherapy 33 times after the biopsy. The patient was admitted to The Military General Hospital of Beijing PLA., Beijing, P.R. China on March 9th, 2011, with chief complaints of right limbs convulsioned suddenly, then fell down and lose of his consciousness, then awoke after 4 to 5 minutes, with symptoms of angulus oris numbness and the right upper limb powerless ten days ago.MRI of the brain revealed a well-defined hyperdense and enhancing mass in the left frontal-parietal lobe, the meninges are closely related, there was extensive peritumoural edema noted with pressure effects, as evident by effacement of the left lateral ventricles and a 0.5 cm shift of the midline to the right side.Surgical resection showed markedly atypical, large singly dispersed or cohesive proliferation of plasmacytoid cells with frequent abnormal mitoses and binucleation, some neoplastic cells were large with round or oval nuclei and showed coarse chromatin and smaller or unapparent nucleoli, some neoplastic cells with prominent nucleoli, apoptosis and necrosis were often presented. Immunohistochemistry staining and gene rearrangement together with other supportive investigation confirmed the diagnosis of primary central nervous system plasmablastic lymphoma. A month later, he was started on chemotherapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, leurocristime and prednisone) for a week. Other supportive treatment was provided for symptomatic epilepsy. The patient regained muscle strength in both upper limbs and right lower limb and the symptomatic epilepsy was controlled after two weeks. Then the patient was discharged. Follow-up data shows the patient to be alive eleven months after discharge., Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1649317674697046.

Recently, it was discovered that high mobility group box chromosomal protein 1 (HMGB1) acts as a potent pro-inflammatory cytokine that is released into the extracellular milieu. Signal transducer and activator of transcription (STAT) proteins play an important role in cytokine signaling. Some investigators have reported preferential activation of STAT1, and others have reported preferential activation of STAT3 in response to endogenous interleukin-6 (IL-6) in patients with rheumatoid arthritis. Here, we show that expression of the HMGB1 protein is increased in the articular tissues of collagen-induced arthritis (CIA) rats, especially in cytoplasm and extracellular, following synoviocyte proliferation and STAT1 activation. In vitro, recombined human HMGB1 induced RSC-364 cell proliferation, activated STAT1 phosphorylation, increased the expression of cyclin D1 and CDK4 protein, and decreased the expression of p21 protein. In summary, our study suggests that HMGB1 plays an important role of cytokine in the pathogenesis of RA, which possibly induces synovial cell proliferation by activating the STAT1 signal pathway.

Background: Ophthalmic gel has been developed to increase the drug concentration in aqueous humor and to retard the loss of drug from the conjunctival sac. The research was to compare the drug concentration in aqueous humor of cataract patients administered 0.3% gatifloxacin ophthalmic gel with that in patients administered 0.3% gatifloxacin ophthalmic solution., Methods: Ninety-six patients with cataract (96 eyes) were randomly assigned to 8 groups. The patients in groups 1-4 received topical gatifloxacin 0.3% ophthalmic gel and those in groups 5-8 received gatifloxacin 0.3% ophthalmic solution. The dose regimen was 1 drop, 4 times a day for 3 consecutive days prior to cataract surgery. On the day of surgery, 1 drop was applied at 15, 30, 60 or 120 minutes before commencement of cataract surgery in groups 1 and 5, groups 2 and 6, groups 3 and 7, and groups 4 and 8, respectively. Aqueous humor was extracted during the cataract surgery for the analysis of gatifloxacin concentration.., Results: The concentrations of gatifloxacin in aqueous humor were (0.24 +/- 0.25) microg/ml, (1.11 +/- 0.74) microg/ml, (2.32 +/- 2.01) microg/ml and (1.85 +/- 1.14) microg/ml in groups 1 to 4, and (0.16 +/- 0.25) microg/ml, (0.31 +/- 0.24) microg/ml, (0.75 +/- 0.28) microg/ml and (0.33 +/- 0.22) microg/ml in groups 5 to 8, respectively. Patients receiving gatifloxacin ophthalmic gel showed greater mean values of gatifloxacin concentration in aqueous humor than those receiving gatifloxacin solution, and such differences were significant with P < 0.05 for all comparisons except that between groups 1 and 5., Conclusion: Topical gatifloxacin ophthalmic gel can attain significantly greater drug concentrations in human aqueous humor than gatifloxacin ophthalmic solution.

In the title compound, C(14)H(15)N(3)OS, the phenyl ring is almost perpendicular to the dimethyl-pyrimidine group, with a dihedral angle of 88.1 (3)°. The Csp(2)-S bond of 1.759 (3) Å is significantly shorter than the Csp(3)-S bond of 1.795 (3) Å due to the p-π conjugation.

Chiral quaternary ammonium salts derived from cinchonidine have been applied to catalyze the stereoselective iodolactonizations of trans-5-aryl-4-pentenoic acids leading to a mixture of two regioselectively iodolactonized products with fair to excellent yield (37-98%) and moderate enantioselectivity (exo = 42.0% ee, endo = 31.0% ee) under mild conditions. This work is the first example of asymmetric iodolactonization reaction in the presence of less than a stoichiometric amount of chiral reagent.

The protective effects of Branched-Chain Amino Acids (BCAA) on ischemic myocardium in rats were studied. Thirty Wistar rats (15 female and 15 male) were randomly divided into 3 groups of 10 animals each. Group A: control; group B: isoproternol (ISO); group C: ISO + BCAA. The rats in groups A and B received normal synthetic rat chow while those in group C received BCAA as supplement. After two weeks of dietary treatment, the rats in group A were injected with saline while those of groups B and C were injected with ISO which induced acute ischemic myocardial injury. After 4 days of injections with either saline or ISO, the rats were sacrificed. The activities of lactate dehydrogenase (LDH), glutamic oxaloacetic transaminase (GOT), alpha-hydroxybutyrate dehydrogenase (alpha-HBDH), creatine kinase (CK), pyruvate kinase (PK) in the serum and in the myocardium, and the concentrations of potassium (K+), magnesium (Mg2+), calcium (Ca2+) in the myocardium were measured. The results showed that the activities of LDH, GOT, alpha-HBDH, CK, PK in the serum and in the myocardium were significantly increased in group B. In addition, the concentrations of Ca2+ in the myocardium were significantly increased. However, the concentrations of Mg2+ in the myocardium were substantially decreased while those of K+ in group B were slightly lowered. In the group C animals both the activities of LDH, alpha-HBDH, PK, CK in the serum and the activities of LDH, GOT, alpha-HBDH, CK in the myocardium were significantly lower than those of the rats in group B, and were not significantly different from those of the control group. More significant was the concentrations of Ca2+ in the myocardium of the rats in group C were comparable to those of the control rats but were significantly lower than those of the rats in group B. It appeared that BCAA was effectively blocking the increase of Ca2+ in the myocardium without raising the level of Mg2+. It was concluded that dietary supplement with BCAA provided some protective effects against ischemic myocardium in rats.