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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

Although the benzimidazole moiety is a versatile heterocyclic unit that has been widely applied in optical materials and medicinal chemistry, there are few bifunctional small-molecule benzimidazole derivatives with bio-activity and fluorescence. In this work, a series of novel benzimidazole-salicylic acid molecules were designed and synthesized; their optical properties were evaluated and their potential biological application was explored. The representative compound 5q exhibited excellent fluorescence properties, displaying blue imaging in HeLa cells and zebrafish. Additionally, it exhibited high selectivity for Fe 3+ ions and demonstrated a notable inhibitory activity with IC 50 = 6.86 ± 2.82 μM against SHP1 PTP . Further effort was applied to explore the potential capability of compound 5q to reactivate the activity of SHP1 when inhibited by Fe 3+ ions, indicating that compound 5q could be a fluorescent modulator to adjust SHP1 enzyme activity in biological systems.

Dysfunction in the SHP1 enzyme can cause cancers and many diseases, so it is of great significance to develop novel small molecule SHP1 inhibitors. Through continuous monitoring of metabolic and targeted processes of SHP1 inhibitors in real-time, we can evaluate the effectiveness and toxicity of the inhibitors, further optimize drug design, and explore SHP1 biology. Indoloquinoxaline is an important class of N-containing heterocycle, which has been studied and applied in the pharmacological field and in optoelectronic materials. In this work, the potential Src homology 2 domain-containing phosphatase 1 (SHP1) inhibitor 5a was developed with the help of the structural fusion and scaffold hop of a fluorophore, 6 H -indolo-[2,3- b ]-quinoxaline, and a bio-active skeleton, thieno[2,3- b ]quinoline-procaine. Compound 5a selectively inhibited the SHP1 PTP enzyme abilities (IC 50 = 2.34 ± 0.06 μM), exhibited a significant fluorescence response ( P = 0.007) in response to SHP1 PTP activity, and emitted strong blue/green fluorescence in MDA-MB-231 cells. Furthermore, compound 5a showed irreversible binding with SHP1 PTP in simulations and dialysis experiments. Altogether, compound 5a serves as a bifunctional SHP1 inhibitor, combining imaging and therapeutic functionalities, enhancing our understanding of SHP1 biological mechanisms, and positively impacting novel drug development.

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.)

Liver fibrosis, one of the leading causes of morbidity and mortality worldwide, lacks effective therapy. The activation of hepatic stellate cells (HSCs) is the dominant event in hepatic fibrogenesis. Luteolin-7-diglucuronide (L7DG) is the major flavonoid extracted from Perilla frutescens and Verbena officinalis. Their beneficial effects in the treatment of liver diseases were well documented. In this study we investigated the anti-fibrotic activities of L7DG and the potential mechanisms. We established TGF-β1-activated mouse primary hepatic stellate cells (pHSCs) and human HSC line LX-2 as in vitro liver fibrosis models. Co-treatment with L7DG (5, 20, 50 μM) dose-dependently decreased TGF-β1-induced expression of fibrotic markers collagen 1, α-SMA and fibronectin. In liver fibrosis mouse models induced by CCl 4 challenge alone or in combination with HFHC diet, administration of L7DG (40, 150 mg·kg -1 ·d -1 , i.g., for 4 or 8 weeks) dose-dependently attenuated hepatic histopathological injury and collagen accumulation, decreased expression of fibrogenic genes. By conducting target prediction, molecular docking and enzyme activity detection, we identified L7DG as a potent inhibitor of protein tyrosine phosphatase 1B (PTP1B) with an IC 50 value of 2.10 µM. Further studies revealed that L7DG inhibited PTP1B activity, up-regulated AMPK phosphorylation and subsequently inhibited HSC activation. This study demonstrates that the phytochemical L7DG may be a potential therapeutic candidate for the treatment of liver fibrosis., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

The development of small fluorescent organic molecules used in bioimaging experiment has boomed the progress of molecular and cellular biology, providing new and efficient tools to elucidate a myriad of cellular and multicellular processes. In this work, a class of fluorescent activators against SHP1 was designed and synthesized for the first time. The representative compound 3n showed activating effect against SHP1 with EC 50 of 17.66 ± 1.48 μM and a fluorescence quantum yield of 0.521 in DMSO. Meanwhile, 3n showed good selectivity for SHP1, inhibited the proliferation of SU-DHL-2 cells and OCI-Ly10 cells with IC 50 of 8.66 ± 1.26 μM and 9.16 ± 0.53 μM and exhibited potential for cellular imaging on human breast cancer cells., 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 © 2025 Elsevier Masson SAS. 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.

The Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP1) is a convergent node for oncogenic cell-signaling cascades. Consequently, SHP1 represents a potential target for drug development in cancer treatment. The development of efficient methods for rapidly tracing and modulating the SHP1 activity in complex biological systems is of considerable significance for advancing the integration of diagnosis and treatment of the related disease. Thus, we designed and synthesized a series of imidazo[1,2,4] triazole derivatives containing salicylic acid to explore novel scaffolds with inhibitory activities and good fluorescence properties for SHP1. The photophysical properties and inhibitory activities of these imidazo[1,2,4] triazole derivatives (5a-5y) against SHP1 PTP were thoroughly studied from the theoretical simulation and experimental application aspects. The representative compound 5p exhibited remarkable fluorescence response (P: 0.002) with fluorescence quantum yield (QY) of 0.37 and inhibitory rate of 85.21 ± 5.17% against SHP1 PTP at the concentration of 100 μM. Furthermore, compound 5p showed obvious aggregation caused quenching (ACQ) effect and had high selectivity for Fe 3+ ions, good anti-interference and relatively low detection limit (5.55 μM). Finally, the cellular imaging test of compound 5p also exhibited good biocompatibility and certain potential biological imaging application. This study provides a potential way to develop molecules with fluorescent properties and bioactivities for SHP1., 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 Elsevier Masson SAS. All rights reserved.)

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).)

Once nanoparticles enter into the biological milieu, nanoparticle-biomacromolecule complexes, especially the protein corona, swiftly form, which cause obvious effects on the physicochemical properties of both nanoparticles and proteins. Here, the thermodynamic parameters of the interactions between water-soluble GSH-CdSe/ZnS core/shell quantum dots (GSH-QDs) and human serum albumin (HSA) were investigated with the aid of labeling fluorescence of HSA. It was proved that the labeling fluorescence originating from a fluorophore (BDP-CN for instance) could be used to investigate the interactions between QDs and HSA. Gel electrophoresis displayed that the binding ratio between HSA and QDs was ∼2:1 by direct visualization. Fluorescence resonance energy transfer (FRET) results indicated that the distance between the QDs and the fluorophore BDP-CN in HSA was 7.2 nm, which indicated that the distance from the fluorophore to the surface of the QDs was ∼4.8 nm. Fluorescence correlation spectroscopy (FCS) results showed that HSA formed a monolayer of a protein corona with a thickness of 5.5 nm. According to the spatial structure of HSA, we could speculate that the binding site of QDs was located at the side edge (not the triangular plane) of HSA with an equilateral triangular prism. The elaboration of the thermodynamic parameters, binding ratio, and interaction orientation will highly improve the fundamental understanding of the formation of protein corona. This work has guiding significance for the exploration of the interactions between proteins and nanomaterials.

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.)

Fluorescence imaging is conducive to establish a bridge between molecular biology and clinical medicine, and provides new tools for disease process research, early diagnosis, and efficacy evaluation, because of the advantages of rapid imaging and nondestructive detection. Herein, a series of fluorescent molecules with thiadiazole, or thiazole, or benzothiazole cores were designed and synthesized to develop more excellent fluorescent molecules in bio-imaging. According to theoretical and experimental methods, we found that benzothiazole derivative 14 B with conjugate expansion by (4-aminophenyl) ethynyl group was the most excellent fluorescent molecule among all the investigated compounds and exhibited low cytotoxicity and strong blue and green fluorescence by confocal cell imaging., (© 2023 Wiley-VCH GmbH.)

Vanadium is a transition metal that naturally occurs in the environment and has a variety of biological and physiological impacts on humans. Sodium orthovanadate (SOV), a well-known chemical compound of vanadium, has shown notable anti-cancer activity in various types of human malignancies. However, the effect of SOV on stomach cancer is yet undetermined. Furthermore, only a few studies have investigated the association of SOV and radiosensitivity with stomach cancer. Our study has investigated the ability of SOV to increase the sensitivity of gastric cancer cells to radiation. To detect autophagy triggered by ionizing radiation and the influence of SOV on cell radiosensitivity, the Cell Counting Kit-8 (CCK8) test, EDU staining experiment, colony formation assay, and immunofluorescence were performed. The possible synergistic effects of SOV and irradiation were examined in vivo using a xenograft mouse model of stomach cancer cells. Both in vitro and in vivo studies showed that SOV markedly reduced the growth of stomach cancer cells and improved their radiosensitivity. Our results showed that SOV increased gastric cancer cells' radiosensitivity, thereby blocking the radiation-induced autophagy-related protein, ATG10. Thus, SOV can be considered a potential agent for radiosensitizing gastric cancer., Competing Interests: Conflicts of Interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Ltd.)

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.

Aim: To obtain promising immunosuppressants from endophytic fungus., Methods and Results: The endophytic fungus Mycosphaerella nawae (ZJLQ129) was isolated from the plant Smilax china L. and its secondary metabolites extracted and fractionated through column chromatography. The metabolites were further modified by a derivatization reaction with ammonium hydroxide. After isolation and derivatization, a new dibenzofuran named as (+)isomycousnine enamine (iME) was obtained. The structures of the derivatives were determined based on chemical evidences and extensive spectroscopic methods including 2D-NMR, DEPT and HRESI-MS spectra. The immune activities of iME were first evaluated on the proliferation and cytokines (IL-2 and IFN-γ) production of T and B cells by using MTT and ELISA methods respectively. Then, its effects on the proliferation of T-cell subsets (CD4 + and CD8 + T cells), as well as CD25 and CD69 expressions were also determined by flow cytometry. Finally, by using Cytometric Bead Array (CBA), the impacts of iME on the secretion of Th1/Th2/Th17 cytokines from purified CD4 + T cells were assayed. The results showed that iME not only selectively suppressed the immune responses of T cells, but also preferentially inhibited the activation and proliferation of CD4 + T cells., Conclusion: A novel dibenzofuran derived from endophytic fungus Mycosphaerella nawae preferentially inhibits CD4 + T-cell activation and proliferation., Significance and Impact of the Study: This work obtained iME, a new dibenzofuran derived from endophytic fungus. iME has the capacity to inhibit CD4 + T-cell activation and therefore is a novel potential immunosuppressant for development in the future., (© 2022 Society for Applied Microbiology.)

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.)

Reported herein is a streamlined protocol to produce pyridylated diarylmethanes through pyridine-boryl radical induced reductive coupling between para-quinone methides (p-QMs) and 4-cyanopyridines using bis(pinacolato)diboron (B 2 pin 2 ) as a templated reagent. The metal-free process is characterized by an operationally simple approach, excellent chemoselectivity (1,2- vs. 1,6-selectivity), and a broad substrate scope with good functional group compatibility. The mechanistic studies provided important insights into the reductive cross-coupling process between diarylmethyl radical and pyridine-boryl radical. Moreover, part of the obtained pyridylated diarylmethane products were screened against a panel of cancer cell lines, and 3 v was confirmed to significantly inhibit the proliferation of head and neck squamous cell carcinoma (HNSCC) cells. This method offers a platform for the preparation of new lead compounds with antitumor activity., (© 2022 Wiley-VCH GmbH.)

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 .

A boron-dipyrromethene (BODIPY)-based fluorescent probe, BDP-CN, was synthesized in this work. It had a fluorescence emission maximum at 512 nm and a high quantum yield (48%). As evidenced by agarose gel electrophoresis and liquid chromatography-mass spectrometry, it could realize the fluorescent labeling of human serum albumin (HSA) through a thiol-cyanimide addition. Interestingly, f-HSA, defined as HSA labeled by BDP-CN, had an even higher quantum yield (77%). In addition, BDP-CN would not affect the secondary structure of HSA. Based on the successful formation of f-HSA, it was further applied to study the interactions with nanoparticles. The fluorescence quenching of f-HSA by dihydrolipoic acid-coated gold nanoclusters (DHLA-AuNCs) obeyed a dynamic mechanism, consistent with the intrinsic fluorescence quenching of HSA by DHLA-AuNCs. The association constant K a between f-HSA and DHLA-AuNCs at 298 K was 1.5 × 10 5 M -1 , which was the same order of magnitude as that between HSA and DHLA-AuNCs. Moreover, the interactions of f-HSA with glutathione-coated gold nanoclusters confirmed that the labeled fluorescence could replace the intrinsic fluorescence to monitor the interactions between proteins and nanoparticles. By this method, strong fluorescence ensures better stability and reproducibility, excitation at a longer wavelength reduces the damage to the proteins, and covalent conjugation with cysteine residues eliminates the inner filter effects to a great extent. Therefore, the strategy for the fluorescent labeling of HSA can be expanded to investigate a broad class of nanoparticle-protein interactions and inspire even more fluorescent labeling methods with organic dyes.

Src homology-2 domain-containing protein tyrosine phosphatase 1 (SHP1) is mainly restricted to hematopoietic and epithelial cells and widely accepted as a convergent node for oncogenic cell-signaling cascades. The development of efficient methods for rapidly tracing and inhibiting the SHP1 activity in complex biological systems is of considerable significance for advancing the integration of diagnosis and treatment of the related disease. With this aim, we designed and synthesized five 2-phenyl-1,3,4-thiadiazole derivatives (PT2, PT5, PT8, PT9 and PT10) here based on the reported SHP1 inhibitors (PT1, PT3, PT4, PT6 and PT7). The photophysical properties and inhibitory activities of these 2-phenyl-1,3,4-thiadiazole derivatives (PT1-PT10) against SHP1 were thoroughly studied from the theoretical simulation and experimental application aspects. The representative compound PT10 exhibited a larger quantum yield than the other molecules because of the smaller geometric relaxation and reorganization energy of the excited state, which was consistent with the results from the fluorescence experiments in organic solvents. In addition, PT10 showed a selective fluorescence response for SHP1 activity and low cytotoxicity in HeLa cells. Lastly, it indicated the potential application in two-photon cell fluorescence imaging in the future according to the calculated excellent two-photon absorption properties. In this contribution, firstly, we offered the fluorescent and activated molecule PT10 against SHP1, which achieved the integration of visualization and inhibitory activity of SHP1 preliminarily at the enzyme molecular level.

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.

With the emergence and rapid development of super-resolution fluorescence microscopy, monitoring of mitochondrial morphological changes has aroused great interest for exploring the role of mitochondria in the process of cell metabolism. However, in the absence of water-soluble, photostable and low-toxicity fluorescent dyes, ultra-high-resolution mitochondrial imaging is still challenging. Herein, we designed two fluorescent BODIPY dyes, namely Mito-BDP 630 and Mito-BDP 760, for mitochondrial imaging. The results proved that Mito-BDP 760 underwent aggregation-caused quenching (ACQ) in the aqueous matrix owing to its hydrophobicity and was inaccessible to the cells, which restricted its applications in mitochondrial imaging. In stark contrast, water-soluble Mito-BDP 630 readily penetrated cellular and mitochondrial membranes for mitochondrial imaging with high dye densities under wash-free conditions as driven by membrane potential. As a comparison, Mito Tracker Red presented high photobleaching (the fluorescence intensity dropped by nearly 50%) and high phototoxicity after irradiation by a laser for 30 min. However, Mito-BDP 630 possessed excellent biocompatibility, photostability and chemical stability. Furthermore, clear and bright mitochondria distribution in living HeLa cells after incubation with Mito-BDP 630 could be observed by CLSM. Convincingly, the morphology and cristae of mitochondria could be visualized using an ultra-high-resolution microscope. In short, Mito-BDP 630 provided a powerful and convenient tool for monitoring mitochondrial morphologies in living cells. Given the facile synthesis, photobleaching resistance and low phototoxicity of Mito-BDP 630, it is an alternative to the commercial Mito Tracker Red.

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.)

The biosafety and efficiency of transplanting retinal pigment epithelial (RPE) cells derived from both human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) have been evaluated in phase I and phase II clinical trials. For further large-scale application, cryopreserved RPE cells must be used; thus, it is highly important to investigate the influence of cryopreservation and thawing on the biological characteristics of hESC-RPE cells and their post-transplantation vision-restoring function. Here, via immunofluorescence, qPCR, transmission electron microscopy, transepithelial electrical resistance, and enzyme-linked immunosorbent assays (ELISAs), we showed that cryopreserved hESC-RPE cells retained the specific gene expression profile, morphology, ultrastructure, and maturity-related functions of induced RPE cells. Additionally, cryopreserved hESC-RPE cells exhibited a polarized monolayer, tight junction, and gap junction structure and an in vitro nanoparticle phagocytosis capability similar to those of induced hESC-RPE cells. However, the level of pigment epithelium-derived factor (PEDF) secretion was significantly decreased in cryopreserved hESC-RPE cells. Royal College of Surgeons rats with cryopreserved hESC-RPE cells engrafted into the subretinal space exhibited a significant decrease in the b-wave amplitude compared with rats engrafted with induced hESC-RPE cells at 4 weeks post transplantation. However, the difference disappeared at 8 weeks and 12 weeks post operation. No significant difference in the outer nuclear layer (ONL) thickness was observed between the two groups. Our data showed that even after cryopreservation and thawing, cryopreserved hESC-RPE cells are still qualified as a donor cell source for cell-based therapy of retinal degenerative diseases., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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.)

Objective: To evaluate the efficacy of triamcinolone acetonide deep fornix injection for the treatment of upper eyelid retraction caused by thyroid-associated ophthalmopathy (TAO). Methods: Case-control study. A retrospective analysis was conducted on 64 eyes in 53 patients with upper eyelid retraction caused by TAO from October 2015 to December 2018. Thirty-nine eyes in 33 patients diagnosed with TAO with upper eyelid retraction were treated with triamcinolone acetonide deep fornix injection (20 mg), once per month until the therapeutic effect was stable, as the treatment group. Twenty-five eyes in 20 patients were not treated (the observation group). The ocular examination indexes of the two groups were compared. Paired t -test and independent sample t -test were used for statistical analysis. Results: There were 6 males and 27 females in the treatment group, aged (43±12) years, and 5 males and 15 females in the observation group, aged (40±13) years. There was no significant difference in gender, age, history and baseline ocular examination indexes between the two groups (all P> 0.05). In the treatment group, the number of injections was (2.18±0.94) times (range, 1 to 5 times). After (6.74±3.89) months of follow-up, the marginal reflex distance (MRD1) was reduced from (6.85±0.88) mm to (4.38±1.04) mm, the score of quality of life in thyroid eye disease (TED-QOL) was reduced from 22.03±4.33 to 7.91±3.25, and the clinical activity score (CAS) was reduced from 2.82±0.39 to 0.97±0.39 ( t= 14.68, 21.36, 20.92; all P< 0.01). There was no statistically significant difference in the degree of exophthalmos, intraocular pressure, the diameter of the rectus muscle measured by B-ultrasound before and after treatment (all P> 0.05). After (8.65±5.15) months of follow-up, the eyelid retraction also improved in the observation group, but the improvement was more obvious in the treatment group. The differences of MRD 1 , TED-QOL and CAS before and after treatment in the treatment group were (2.46±1.05) mm, 14.06±3.80 and 1.85±0.51 respectively, which were significantly higher than those before and after the follow-up in the observation group [(0.32±0.75) mm, 3.24±2.86 and 0.56±0.58, respectively; t= 8.86, 11.90, 8.98; all P< 0.01]. There was no recurrence in the two groups. In the treatment group, 5 patients (6 eyes) showed a transient intraocular pressure rise, which was controlled after medication; 3 women had menstrual changes. Conclusions: Deep fornix injection of triamcinolone acetonide for treating upper eyelid retraction is convenient and effective. It can significantly reduce symptoms and improve patients' quality of life. (Chin J Ophthalmol, 2020, 56:524-529) .

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. Consequently, SHP2 has emerged as a compelling target for novel anti-cancer agents. Replacing one of phenyl ring in PTP1B inhibitor 1 with heterocyclic ring led to a series of heterocyclic bis-aryl amide derivatives. The representative compound 7b displayed SHP2 inhibitory activity with IC 50 of 2.63 ± 0.08 μM, exhibited about 4-fold selectivity for SHP2 over TCPTP and had no detectable activity against SHP1 and PTP1B. These preliminary results could provide a possible opportunity for the development of novel SHP2 inhibitors with optimal potency and improved pharmacological properties., 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.)

The overexpression of NIK plays a critical role in liver inflammatory diseases. Treatment of such diseases with small-molecule NIK inhibitors is a reasonable but underexplored approach. In this paper, we reported the discovery of a potent and selective NIK inhibitor 46 (XT2). 46 inhibited the NIK kinase with an IC 50 value of 9.1 nM in vitro, and it also potently suppressed NIK activities in intact cells. In isogenic primary hepatocytes, treatment of 46 efficiently suppressed the expressions of NIK-induced genes. 46 was orally bioavailable in mice with moderate systemic exposure. In a NIK-associated mouse liver inflammation model, 46 suppressed CCl 4 -induced upregulation of ALT, a key biomarker of acute liver injury. 46 also decreased immune cell infiltration into the injured liver tissue. Overall, these studies provide examples that an NIK inhibitor is able to suppress toxin-induced liver inflammations, which indicates its therapeutic potentials for the treatment of liver inflammatory diseases.

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.

Background: Patients with Meniere's disease (MD) may present with peripheral vestibular end organ dysfunction and balance dysfunction. Objective: This study aimed to compare the results of vestibular evoked myogenic potential (VEMP) tests with those of the sensory organization test (SOT) in patients with MD to determine whether they are correlated. Material and methods: In total, 132 patients with unilateral MD were evaluated using an audiometric test, the SOT, a caloric test and VEMP tests. Results: Cervical VEMP and ocular VEMP tests were conducted in 132 patients with MD, and the response rates of the affected side were lower than those of the unaffected side. The composite score, C5 ES , and C6 ES of the SOT were significantly decreased in patients with no VEMP responses compared to those with VEMP responses. Conclusions and significance: MD patients with no VEMP responses are more likely to develop balance impairment than those with VEMP responses. MD patients with otolith organ impairment may therefore have balance disorders, and should exercise caution to prevent falls and subsequent injuries.

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.

Objective: To explore the correlation between the rs2067853 polymorphism in angiotensinogen (AGT) gene and neonatal hypoxic-ischemic encephalopathy (HIE)., Patients and Methods: A total of 96 neonatal patients with HIE and 123 healthy neonates were selected. General clinical data were collected and TaqMan-MGB probe method was adopted to detect the rs2067853 polymorphism in angiotensinogen (AGT) gene., Results: The frequency of advanced maternal age, low maternal age, maternal renal insufficiency, abnormal labor, amniotic fluid contamination and umbilical cord abnormality in the observation group was higher than that in the control group (p<0.05), and there was no significant difference between the two groups in the frequency of pregnancy-induced hypertension or eclampsia, maternal anemia, routine prenatal examination, natural childbirth, placental abnormality and abnormal birth weight (p>0.05). There was a difference in genotype distribution frequency between the two groups (p<0.05), while there was no difference in the allele distribution frequency between the two groups (p>0.05). The recessive model had differences between the two groups (p<0.05), while the dominant and additive model had no differences between the two groups (p>0.05)., Conclusions: HIE is correlated with maternal factors, fetal growth, uterine environment and labor process, and the rs2067853 polymorphism in AGT gene is associated with HIE.

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.)

Objective: To define clinical and laboratory characteristics of bilateral vestibulopathy(BVP) and to propose diagnostic criteria of this disorder based on clinical and laboratory vestibular function test findings. Method: Forty-two case series with a clinical suspicion of BVP were retrospectively analyzed, in an attempt to determine etiology. Presenting auditory-vestibular symptoms, bedside dynamic visual acuity tests and laboratory test were reviewed, including bithermal caloric test, rotatory chair tests, video head impulse test (vHIT), vestibular-evoked myogenic potentials (VEMP). Result: Among these 42 patients, dizziness was seen in 42 cases(100%), oscillopsia was seen in 21 cases(50%), hearing loss was seen in 30(71.4%). Eight cases(19%) had tinnitus. Twenty-five cases showed vestibular loss in dynamic visual acuity test (69.4%). Definite diagnosis of complete BVP was made in 36 patients when the patients showed abnormal findings on caloric test, rotatory chair test and vHIT in addition to the symptoms. Whereas probable diagnosis of partial BVP was obtained in 6 patients with abnormal caloric test and rotatory chair test but no pathological vHIT. VEMP (ocular or cervical) could be recorded in 20 patients. Fourteen cases were caused by ototoxic drugs while no causes could be determined in 6 cases among these 42 cases. Conclusion: The diagnosis of BVP is a challenge. Vestibular laboratory test battery which reflect full frequency function of VOR has great value to confirming the diagnosis and differentiate complete BVP to partial BVP. Diagnosis standard shall be made combining clinical history, characteristic symptoms and the results of auditory-vestibular function testing. Ototoxic drugs contribute most considering etiology., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Main Conclusion: Application of auxin to root stock and scion increases the success rate of grafting in Chinese hickory. The nuts of the Chinese hickory (Carya cathayensis) tree are considered both delicious and healthy. The popularity and high demand result is that the hickory nuts are of very high economical value for horticulture. This is particularly true for the Zhejiang province in eastern China where this tree is widely cultivated. However, there are several difficulties surrounding the hickory cultivation, such as for example long vegetative growth, tall trees, labour-intensive nut picking, and slow variety improvements. These complications form a great bottleneck in the expansion of the hickory industry. The development of an efficient grafting procedure could surpass at least some of these problems. In this study, we demonstrate that application of the auxin indole-3-acetic acid promotes the grafting process in hickory, whereas application of the auxin transport inhibitor 1-N-naphthylphthalamic acid inhibits the grafting process. Furthermore, we have identified hickory genes in the PIN, ABCB, and AUX/LAX-families known to encode influx and efflux carriers in the polar transport of auxin. We show that increased expression of several of these genes, such as CcPIN1b and CcLAX3, is correlating with successful grafting.