Search

Cheng-Ting Zi,1,2,* Liu Yang,2,* Qing-Hua Kong,2 Hong-Mei Li,2 Xing-Zhi Yang,2 Zhong-Tao Ding,3 Zi-Hua Jiang,4 Jiang-Miao Hu,2 Jun Zhou2 1Key Laboratory of Pu-Er Tea Science, Ministry of Education, College of Science, Yunnan Agricultural University, Kunming, 650201, People’s Republic of China; 2State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People’s Republic of China; 3Key Laboratory of Medicinal Chemistry for Nature Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, People’s Republic of China; 4Department of Chemistry, Lakehead University, Thunder Bay ON P7B 5E1, Canada*These authors contributed equally to this workCorrespondence: Zi-Hua JiangDepartment of Chemistry, Lakehead University, 955 Oliver Road, Thunder Bay ON P7B 5EI, CanadaTel +1 807 766 7171Fax +1 807 346 7775Email zjiang@lakeheadu.caJiang-Miao HuState Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, No. 132, Lanhei Road, Kunming 650201, People’s Republic of ChinaTel +86 871 6522 3264Fax +86 871 6522 3261Email hujiangmiao@mail.kib.ac.cnBackground: Widespread concern of the side effects and the broad-spectrum anticancer property of podophyllotoxin as an antitumor agent highlight the need for the development of new podophyllotoxin derivatives. Although some per-butyrylated glucosides of podophyllotoxin and 4β-triazolyl-podophyllotoxin glycosides show good anticancer activity, the per-acetylated/free of podophyllotoxin glucosides and their per-acetylated are not well studied.Methods: A few glucoside derivatives of PPT were synthesized and evaluated for their in vitro cytotoxic activities against five human cancer cell lines, HL-60 (leukemia), SMMC-7721 (hepatoma), A-549 (lung cancer), MCF-7 (breast cancer), and SW480 (colon cancer), as well as the normal human pulmonary epithelial cell line (BEAS-2B). In addition, we investigated the structure–activity relationship and the physicochemical property–anticancer activity relationship of these compounds.Results: Compound 6b shows the highest cytotoxic potency against all five cancer cell lines tested, with IC50 values ranging from 3.27±0.21 to 11.37±0.52 μM. We have also found that 6b displays higher selectivity than the etoposide except in the case of HL-60 cell line. The active compounds possess similar physicochemical properties: MSA > 900, %PSA < 20, ClogP > 2, MW > 700 Da, and RB > 10.Conclusion: We synthesized several glucoside derivatives of PPT and tested their cytotoxicity. Among them, compound 6b showed the highest cytotoxicity. Further studies including selectivity of active compounds have shown that the selectivity indexes of 6b are much greater than the etoposide except in the case of HL-60 cell line. The active compounds possessed similar physicochemical properties. This study indicates that active glucoside analogs of podophyllotoxin have potential as lead compounds for developing novel anticancer agents.Keywords: podophyllotoxin, glucoside, synthesis, cytotoxicity, physicochemical properties

Li Zhou,1,2 Qinghuan Kong,3 Yunhan Zhang,3 Wei Yang,4 Shan Yan,3 Meihui Li,3 Yidan Wang,3 Yanjie Zhou,3 Huimei Yu,3 Liying Han1 1Department of Obstetrics and Gynecology, The Second Hospital of Jilin University, Changchun 130041, China; 2Department of Obstetrics and Gynecology, The First Hospital of Jilin University, Changchun 130021, China; 3Department of Pathology and Pathophysiology, School of Basic Medical Sciences, Jilin University, Changchun 130021, China; 4Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun 130021, China Background: S1 is a novel BH3 mimetic that can induce death in some types of cancer cells, such as melanoma B16, ovarian cancer SKOV3, and U251 glioma cells. S1 inhibits Bcl-2 and Mcl-1 expression and induces cancer cell apoptosis. Cancer cell survival is highly dependent on glucose. Here, we observed the effect of glucose deprivation on the apoptotic response to S1 in human cervical cancer (HeLa) cells.Materials and methods: Earle’s balanced salt solution (EBSS) was used to simulate glucose deprivation. MTT assay was used to analyze the cell survival rate, and Hoechst 33342 dye was used to detect the apoptosis in HeLa cells. Western blotting was used to detect the expression of ER stress and autophagy relative proteins. In addition, lysosomes were observed with LysoTracker staining by confocal microscopy.Results: S1 decreased cell distribution density and survival rate, and MTT assay showed that EBSS enhanced the inhibitory effects of S1 on HeLa cell growth. Hoechst 33342 dye showed that S1 led to pyknosis, fragmentation, and strong staining in HeLa cell nuclei, and EBSS enhanced these effects. Western blotting indicated that EBSS enhanced the expression of apoptosis-related proteins (cytochrome C, caspase-3, and poly[ADP-ribose] polymerase 1) induced by S1 in HeLa cells. S1 decreased p62 expression and increased the autophagosome-associated protein LC3-II expression, which indicated that S1 induced autophagy in HeLa cells. EBSS enhanced S1-induced autophagy in HeLa cells. Furthermore, autophagy inhibitor chloroquine enhanced S1-induced apoptosis in HeLa cells.Conclusion: These results indicate that EBSS exacerbates S1-induced autophagy and severe autophagy induced by EBSS and S1 could lead to apoptosis in HeLa cells. The results also suggest that EBSS enhances the sensitivity of HeLa cells to S1-induced apoptosis and that autophagy plays an important role in this process. Keywords: Earle’s balanced salt solution, glucose deprivation, S1, endoplasmic reticulum stress, autophagy, apoptosis

Xiao-ru Wang,1,* Yong-pu Li,2,* Shui Gao,2 Wei Xia,2 Kun Gao,1 Qing-hua Kong,1 Hui Qi,1 Ling Wu,1 Jing Zhang,3 Jie-ming Qu,4 Chun-xue Bai3 1Department of Pulmonary Medicine, Dahua Hospital, Xuhui District, Shanghai, 2Department of Pulmonary Medicine, People's Hospital of Changshou, Chongqing, 3Department of Pulmonary Medicine, Zhongshan Hospital, 4Department of Pulmonary Medicine, Huadong Hospital, Fudan University, Shanghai, People's Republic of China *These two authors contributed to this paper equally Abstract: Despite a number of studies on biomarkers in chronic obstructive pulmonary disease (COPD), only a few disease-related markers have been identified, yet we still have no satisfactory markers specific to innate immune system and neutrophil activation, which is essential in airway inflammation in COPD. Recent biological studies indicated that lipocalins (LCNs) might be involved in airway inflammation and innate immunity; however, results from available studies on the association of LCNs with COPD are not consistent. We carried out a multicenter prospective observational cohort study to investigate the differences in serum levels of LCN1 and LCN2 between subjects with COPD (n=58) and healthy controls (n=29). Several validated inflammatory markers, including C-reactive protein, tumor necrosis factor-a, interleukin-6, and interleukin-8, were measured. The correlation of LCN1 and LCN2 with clinical features such as smoking habits, lung function, symptoms, and disease category was also analyzed. When comparing with healthy controls, serum levels of LCN1 (66.35±20.26 ng/mL versus 41.16±24.19 ng/mL, P

Cytochrome P450 2D6 (CYP2D6) exhibits rich genetic polymorphism, and functional changes caused by variations are the key reasons for differences in substrate drug systemic exposure. Discovering novel variants and defining their enzymatic kinetic characteristics can contribute to the personalized application of drugs. In this study, a data chain of variant-function-structure was established through population-based sequencing, baculovirus insect cell expression, in vitro enzymatic incubation, and ultrahigh performance liquid chromatography tandem mass spectrometry. Results revealed nine novel missense mutations in the exonic regions. After the corresponding microsomes were obtained, the kinetics of the variants were investigated using dextromethorphan as a probe substrate. It was found that the activities of CYP2D6.2, 10, 17, 35, 65, R28G, T76M, and E215K were significantly reduced, while D301V almost led to loss of enzyme function. Additionally, the relative clearance rate of R25Q was significantly increased. From the molecular structure perspective, the mutation sites are distributed outside the dextromethorphan binding pocket, suggesting that they primarily influence CYP2D6 activity via allosteric modulation. These research findings provide fundamental data for the precise application of CYP2D6 substrate drugs.

Ethnopharmacological Relevance: Tilia tuan Szyszyl. is a perennial arboreal plant renowned for its medicinal and economic significance. All the roots, stems, leaves, flowers, and fruits have been used medicinally by the folk Bai and Yi people in Yunnan province, China, to treat inflammation, rheumatism and pain for a long time. The detailed chemical constituents and their anti-inflammatory mechanisms remain unexplored., Aim of the Study: The objective of this study was to investigate the main anti-inflammatory constituents of T. tuan flowers through bio-guided isolation and to evaluate their anti-inflammatory effects relevant to its traditional medicinal use., Material and Methods: Bio-guided isolation was conducted on the extract of T. tuan flowers using a combination of column chromatography and preparative HPLC. The structures were established by a combination of extensive spectroscopic analyses and single-crystal X-ray diffraction analysis. The anti-inflammatory activity in vitro was evaluated by measuring the inhibition of nitric oxide (NO) production in LPS-stimulated RAW 264.7 cells. TNF-α and IL-6 levels were evaluated by ELISA. The expression of COX-2 and NF-κB was assayed via western blotting, and in-silico molecular docking was conducted to explore the potential mechanism., Results: Twenty-two compounds, including ten flavonoids (1-10), seven phenylpropanoids (11-17), three triterpenoids (19-21), one sterol glucoside 18, and one glyceride 22, were identified from T. tuan flowers for the first time. Among them, 1 is a new compound. It is noted that 1, 5, 7, 8, 10, 17, and 22 exhibited remarkable anti-inflammatory activity against NO production with a range of 5.2-34.5 μM, superior to the positive control L-NMMA. Moreover, the new compound 1 inhibited significantly inflammatory factors IL-6 and TNF-α., Conclusion: The results show that flavonoids including the new one and the phenyl-propanoid are the primary active constituents of T. tuan flowers, responsible for its ethno-pharmacological uses on osteoarthritis and rheumatism. T. tuan flowers could be a promising therapeutic agent to modulate inflammatory diseases., 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 © 2024 Elsevier B.V. All rights reserved.)

A new naphthoquinone derivative ( 1 ) together with twenty-three known compounds ( 2 - 24 ), were isolated from the aerial parts of Rubia cordifolia L. Their structures were elucidated on the basis of NMR and HR-ESIMS data. Compounds 1 - 13 were assessed for their inhibitory effects on NO production in LPS-stimulated RAW 264.7 macrophage cells. Compounds 2 - 6 exhibited significant inhibitory activities with IC 50 values of 21.37, 13.81, 24.56, 20.32, and 30.08 μmol·L -1 , respectively.

The mechanisms of testicular development in mammals are complex. Testis is an organ that produces sperm and secretes androgens. It is rich in exosomes and cytokines that mediate signal transduction between tubule germ cells and distal cells, promoting testicular development and spermatogenesis. Exosomes are nanoscale extracellular vesicles that transmit information between cells. By transmitting information, exosomes play an important role in male infertility diseases such as azoospermia, varicocele, and testicular torsion. However, due to the wide range of sources of exosomes, extraction methods are numerous and complex. Therefore, there are many difficulties in studying the mechanisms of exosomal effects on normal development and male infertility. Therefore, in this review, first, we introduce the formation of exosomes and methods for culturing testis and sperm. Then, we introduce the effects of exosomes on different stages of testicular development. Finally, we summarize the prospects and shortcomings of exosomes when used in clinical applications. We lay the theoretical foundation for the mechanism of the influence of exosomes on normal development and male infertility., (Copyright © 2023 Copyright: © The Author(s)(2023).)

Versatile electrocatalysis at higher current densities for natural seawater splitting to produce hydrogen demands active and robust catalysts to overcome the severe chloride corrosion, competing chlorine evolution, and catalyst poisoning. Hereto, the core-shell-structured heterostructures composed of amorphous NiFe hydroxide layer capped Ni 3 S 2 nanopyramids which are directly grown on nickel foam skeleton (NiS@LDH/NF) are rationally prepared to regulate cooperatively electronic structure and mass transport for boosting oxygen evolution reaction (OER) performance at larger current densities. The prepared NiS@LDH/NF delivers the anodic current density of 1000 mA cm -2 at the overpotential of 341 mV in 1.0 m KOH seawater. The feasible surface reconstruction of Ni 3 S 2 -FeNi LDH interfaces improves the chemical stability and corrosion resistance, ensuring the robust electrocatalytic activity in seawater electrolytes for continuous and stable oxygen evolution without any hypochlorite production. Meanwhile, the designed Ni 3 S 2 nanopyramids coated with FeNi 2 P layer (NiS@FeNiP/NF) still exhibit the improved hydrogen evolution reaction (HER) activity in 1.0 m KOH seawater. Furthermore, the NiS@FeNiP/NF||NiS@LDH/NF pair requires cell voltage of 1.636 V to attain 100 mA cm -2 with a 100% Faradaic efficiency, exhibiting tremendous potential for hydrogen production from seawater., (© 2023 Wiley-VCH GmbH.)

Eleven flavonoids including one new flavonol glycoside, quercetin-3- O -(2- α -L-rhamnopyranosyl)- β -D-glucuronopyranosyl methyl ester (1), were isolated for the first time from the fruits of Phyllanthus acidus (L.) Skeels (Phyllanthaceae). Their structures were determined by extensive spectroscopic data. The known flavonoids, quercetin-3- O - β -D-glucuronide methyl ester (3), quercetin-3- O -(2''- α -L-rhamnopyranosyl-6''- O - α -L-rhamno pyranosyl)- β -D-glucopyranoside ( 5 ), myricetin ( 9 ), and 6-methoxy-naringenin ( 11 ) were isolated for the first time from the genus Phyllanthus . Flavonoids 4 , 6 and 9 (IC 50 = 6.01, 6.32, and 7.84 μM, respectively) showed stronger α -glucosidase inhibitory activities than the positive control, acarbose (IC 50 = 306.45 μM). The fruits of P. acidus might be further developed as an anti-diabetic food supplement.

Heterogeneous electrocatalysis typically depends on the surface electronic states of active sites. Modulating the surface charge state of an electrocatalysts can be employed to improve performance. Among all the investigated materials, nickel (Ni)-based catalysts are the only non-noble-metal-based alternatives for both hydrogen oxidation and evolution reactions (HOR and HER) in alkaline electrolyte, while their activities should be further improved because of the unfavorable hydrogen adsorption behavior. Hereto, Ni with exceptional HOR electrocatalytic performance by changing the d-band center by metal oxides interface coupling formed in situ is endowed. The resultant MoO 2 coupled Ni heterostructures exhibit an apparent HOR activity, even approaching to that of commercial 20% Pt/C benchmark, but with better long-term stability in alkaline electrolyte. An exceptional HER performance is also achieved by the Ni-MoO 2 heterostructures. The experiment results are rationalized by the theoretical calculations, which indicate that coupling MoO 2 with Ni results in the downshift of d-band center of Ni, and thus weakens hydrogen adsorption and benefits for hydroxyl adsorption. This concept is further proved by other metal oxides (e.g., CeO 2 , V 2 O 3 , WO 3 , Cr 2 O 3 )-formed Ni-based heterostructures to engineer efficient hydrogen electrocatalysts., (© 2022 Wiley-VCH GmbH.)

Foxtail millet ( Setaria italica ) is a versatile grain and fodder crop grown in arid and semi-arid regions. It is an especially important crop for combating malnutrition in certain poverty-stricken areas of the world. Photoperiod sensitivity is a major constraint to the distribution and utilization of foxtail millet germplasm resources. Foxtail millet may be suitable as a model species for studying the photoperiod sensitivity of C 4 crops. However, the genetic basis of the photoperiod response of foxtail millet remains poorly studied. To detect the genetic basis of photoperiod sensitivity-related traits, a recombinant inbred line (RIL) population consisting of 313 lines derived from a cross between the spring-sown cultivar "Longgu 3" and the summer-sown cultivar "Canggu 3" was established. The RIL population was genotyped using whole-genome re-sequencing and was phenotyped in four environments. A high-density genetic linkage map was constructed with an average distance between adjacent markers of 0.69 cM. A total of 21 quantitative trait loci (QTLs) were identified by composite interval mapping, and 116 candidate genes were predicted according to gene annotations and variations between parents, among which three genes were considered important candidate genes by the integration and overall consideration of the results from gene annotation, SNP and indel analysis, cis -element analysis, and the expression pattern of different genes in different varieties, which have different photoperiod sensitivities. A putative candidate gene, SiCOL5 , was isolated based on QTL mapping analysis. The expression of SiCOL5 was sensitive to photoperiod and was regulated by biological rhythm-related genes. Function analysis suggested that SiCOL5 positively regulated flowering time. Yeast two-hybrid and bimolecular fluorescence complementation assays showed that SiCOL5 was capable of interacting with SiNF-YA1 in the nucleus., 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 Li, Niu, Yu, Kong, Wang, Qin, Chen, Yang, Liu, Lang, Zhang, Wang and Guan.)

Retinitis pigmentosa is a retinal disease characterized by photoreceptor degeneration. There is currently no effective treatment for retinitis pigmentosa. Although a mixture of lutein and other antioxidant agents has shown promising effects in protecting the retina from degeneration, the role of lutein alone remains unclear. In this study, we administered intragastric lutein to Pde6b rd10 model mice, which display degeneration of retinal photoreceptors, on postnatal days 17 (P17) to P25, when rod apoptosis reaches peak. Lutein at the optimal protective dose of 200 mg/kg promoted the survival of photoreceptors compared with vehicle control. Lutein increased rhodopsin expression in rod cells and opsin expression in cone cells, in line with an increased survival rate of photoreceptors. Functionally, lutein improved visual behavior, visual acuity, and retinal electroretinogram responses in Pde6b rd10 mice. Mechanistically, lutein reduced the expression of glial fibrillary acidic protein in Müller glial cells. The results of this study confirm the ability of lutein to postpone photoreceptor degeneration by reducing reactive gliosis of Müller cells in the retina and exerting anti-inflammatory effects. This study was approved by the Laboratory Animal Ethics Committee of Jinan University (approval No. LACUC-20181217-02) on December 17, 2018., Competing Interests: None

The present study aimed to identify the composition of the aerial parts of Rubia cordifolia L. A chemical investigation on the EtOAc extracts from the aerial parts of Rubia cordifolia resulted in the isolation of four new anthraquinones, namely Cordifoquinone A-D ( 1 - 4 ), along with 16 known anthraquinones. Their structures were elucidated on the basis of NMR and HR-ESIMS data. All isolates were assessed for their inhibitory effects on NO production in LPS-stimulated RAW 264.7 macrophage cells. Compounds 1 , 3 and 10 exhibited significant inhibitory activities with IC 50 values of 14.05, 23.48 and 29.23 μmol·L -1 , respectively. Their antibacterial activities of four bacteria, Escherichia coli (ATCC 25922), Staphylococcus aureus subsp. aureus (ATCC 29213), Salmonella enterica subsp. enterica (ATCC 14028) and Pseudomonas aeruginosa (ATCC 27853), were also evaluated. Our results indicated that the antibacterial activity of these compounds is inactive.

Two new (-)-epigallocatechin-3-gallate-4β-triazolopodophyllotoxin conjugates ( 7 and 8 ) were synthesized and evaluated for biological activity. Compound 8 showed highly potent anticancer activity against A-549 cell line with IC 50 of 2.16 ± 1.02 μM, which displayed the highest selectivity index value (SI = 14.5) in A-549 cells. Molecular docking indicated that compound 8 could bind with the active site of Top-II. Therefore, compound 8 might be a promising candidate for further development.

Ethnopharmacological Relevance: Terminalia chebula (TC), a well-known Indian Ayurvedic medicine introduced into China in the Sui and Tang Dynasties, has been recorded and used medicinally as Fructus Chebulae, together with its variety tomentella (TCT) in the Chinese Pharmacopoeia. They have been also used commonly for the treatment of diabetes mellitus by Tibetan medicine., Aim of the Study: To investigate the main bioactive and therapeutic principles in the fruits of TCT, based on the extensive evaluation of their anti-inflammatory and hypoglycemic activities., Materials and Methods: The TCT fresh fruits were analyzed by HPLC and separated further by column chromatography and preparative HPLC. The isolated compounds were identified by extensive spectroscopic analyses, including 1D/2D NMR, MS, UV, IR and ECD. Anti-inflammatory activity was evaluated by inhibition of NO production in RAW264.7 cells. The specific iNOS (PDB ID: 3E7G) structure was prepared by Discovery Studio 4.0, and the molecular docking simulation was performed on GOLD (version 5.2.2). Hypoglycemic activity was measured using the substrate solution of 4-nitrophenyl-α-d-glucopyranoside enzyme and buffer solution., Results: The HPLC analysis method of polyphenols in the fruits of TCT was established, and 13 main chromatographic peaks were identified, including six hydrolyzable tannins (2, 4-7, 10-11), three simple phenols (12-14), and one oleanane pentacyclic triterpene, arjungenin. Extensive chromatographic separation of TCT fresh fruits yielded 14 compounds, including one new natural hydrolyzable tannin, 2,3-(S)-HHDP-6-O-galloyl-d-glucose (1). The known compounds were identified as 10 hydrolyzable tannins (2-11) and three simple phenols (12-14). Compounds 10 (IC 50  = 36.43 ± 0.21 μM), 11 (IC 50  = 42.28 ± 0.09 μM) displayed stronger NO inhibitory activity than the positive control L-NMMA (IC 50  = 42.34 ± 0.66 μM), while 2, 4, and 9 showed moderate inhibitory activity against NO production. Further molecular docking simulation of specific iNOS on 10 and 11, as well as five previously isolated lignans 15-19 showed that there were no obvious rules between docking results and the in vitro NO inhibitory activity for hydrolyzable tannins (10 and 11), while the mechanism of anti-inflammatory activity for lignans was related to the substitution of conjugated aldehyde groups. Moreover, most of the hydrolyzable tannins (1-2, 4-5, 9-11) and simple phenol (12) displayed stronger inhibitory effects on α-glucosidase than the positive control, quercetin (IC 50  = 6.118 ± 0.071 μM), with IC 50 values ranging from 0.079 to 16.494 μM. Among these bioactive isolates, the hydrolyzable tannins 2, 4-5, and 9-11, and simple phenol 12 are major chemical components in TCT fruit., Conclusions: The results showed that lignans and hydrolyzed tannins are the main active ingredients of TCT fruits, responsible for the traditional treatment of sore throat and cough. Moreover, hydrolyzed tannins and simple phenolic compounds with potential hypoglycemic activity are closely related to the ethno-pharmacological uses of TCT fruits on diabetes in Tibetan medicine., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background and Objective: Retinopathy of prematurity (ROP), a proliferative vascular eye disease, is one of the leading causes of blindness in childhood and prevails in premature infants with low-birth-weight. The recent progress in digital image analysis offers novel strategies for ROP diagnosis. This paper provides a comprehensive review on the development of digital diagnosing systems for ROP to software researchers. It may also be adopted as a guide to ophthalmologists for selecting the most suitable diagnostic software in the clinical setting, particularly for the remote ophthalmic support., Methods: We review the latest literatures concerning the application of digital diagnosing systems for ROP. The diagnosing systems are analyzed and categorized. Articles published between 1998 and 2020 were screened with the two searching engines Pubmed and Google Scholar., Results: Telemedicine is a method of remote image interpretation that can provide medical service to remote regions, and yet requires training to local operators. On the basis of image collection in telemedicine, computer-based image analytical systems for ROP were later developed. So far, the aforementioned systems have been mainly developed by virtue of classic machine learning, deep learning (DL) and multiple machine learning. During the past two decades, various computer-aided systems for ROP based on classic machine learning (e.g. RISA, ROPtool, CAIER) became available and have achieved satisfactory performance. Further, automated systems for ROP diagnosis based on DL are developed for clinical applications and exhibit high accuracy. Moreover, multiple instance learning is another method to establish an automated system for ROP detection besides DL, which, however, warrants further investigation in future., Conclusion: At present, the incorporation of computer-based image analysis with telemedicine potentially enables the detection, supervision and in-time treatment of ROP for the preterm babies., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To investigate the effects of orthokeratology on biological parameters and visual quality of adolescents with low-grade corneal astigmatism myopia., Patients and Methods: In this study, a total of 41 myopic adolescents were prescribed with orthokeratology glasses in our hospital from February 2018 to March 2019 and voluntarily cooperated with relevant examinations before and after wearing orthokeratology lenses. Patients' uncorrected distant visual acuity (UCVA-D), uncorrected near visual acuity (UCVA-N) and naked eye near stereoacuity before wearing glasses, 1 month, and 3 months after wearing glasses were observed. The corneal astigmatism of patients was observed. The corneal endothelial cell density was observed. The dynamic adjustment function (NP, AF, NRA, PRA) values of patients were observed. The comparison of biological indexes in different time periods was observed. The changes of corneal curvature before wearing orthokeratology lens, 1 month and 3 months after wearing orthokeratology lens were observed., Results: There were significant changes of patients 1 month after wearing orthokeratology lenses (p < 0.05), while there was no significant difference between 3 months after wearing the orthokeratology lenses and 1 month after wearing the orthokeratology lenses (p < 0.05). Patients' NCAV-D and UCVA-N were recorded by a conversion method of 5 points. There were differences in the NCVA-D, NCVA-N, naked eye near stereoacuity before, 1 month, and 3 months after wearing glasses (p < 0.05). By observing patients' biological indicators and dynamic adjustment, it was found that there were statistically significant differences in NP, AF, BRA and PRA before wearing the glasses, 1 month and 3 months after wearing the glasses (p < 0.05)., Conclusions: The use of orthokeratology can greatly correct myopia patients' vision, improve their stereoscopic vision, control the progression of myopia, and improve their eye regulation, which is of high safety and great short-term effect.

Two new compounds ( 9 and 10 ) having a camptothecin (CPT) analog conjugated to the 4β-azido-4-deoxypodophyllotixin analog by untilizing the copper-catalyzed azide-alkyne cycloadditon (CuAAC) reaction, and were evaluated for their cytotoxicity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7 and SW480) using the MTT (3-(4,5-dimethyl-thiahiazo-2-yl)-2,5-diphenyltetrazolium bromide) assay. Two novel conjugates shown weak cytotoxicity, compound 10 showed highly potent against HL-60 cell line tested, with IC 50 value 17.69 ± 0.19 μM. This compound suggested its potential as anticancer agents for further development. [Formula: see text].

The electrosynthesis of high-value ethanol from carbon dioxide and carbon monoxide addresses the need for the large-scale storage of renewable electricity and reduction of carbon emissions. However, the electrosynthesis of ethanol by the CO 2 reduction reaction (CO 2 RR) has suffered from low selectivity and energy efficiency. Here, we report a catalyst composed of Au nanoparticles in Cu 2 O nanocavities (Au@Cu 2 O) that is very active for CO 2 reduction to ethanol through the confinement of the CO intermediate. The architecture shows tandem catalysis mechanisms in which CO 2 reduction on Au yolks produces CO filling Cu nanocavities, where a sufficiently high CO concentration due to the confinement effect promotes ethanol formation and then results in an ethanol faradaic efficiency of 52.3% at -0.30 V versus the reversible hydrogen electrode ( vs. RHE) via regulating the hollow size of the Cu 2 O nanocavities. Such a strategy provides a new way of fabricating various tandem catalysts with high selectivity and efficiency for the CO 2 RR., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

To improve lithium storage performances of Si anode for lithium-ion batteries, Si nanoparticles encapsulated into porous N-doped carbon (Si@PNC) was devised and prepared by metal nitrate accelerated polymer blowing process. The Si@PNC composites have large specific surface area of 221.7 m² g -1 and possess a great deal of mesopores and micropores, which are attributed to the carbonization of PVP and etching metallic nanoparticles. As anode for lithium ion battery, the initial discharge capacity of Si@PNC composites is high to 1626 mA h g -1 , and the specific capacity still retains 1030 mA h g -1 after 200 cycles at 200 mA g -1 . Meanwhile, remarkably improved rate capability is achieved with an excellent reversible specific capacity of 375 mA h g -1 at 5.0 A g -1 . The excellent lithium storage performances benefit from the unique porous core-shell structure of Si@PNC composites, which improve electroconductivity, reduce volume dilatation and accelerate lithium ion transmission.

Objective : The purpose of this prospective study was to investigate the perceptions and attitudes to participate in radical and palliative clinical trials among Chinese lymphoma and head/neck cancer patients. Patients and Methods : A self-developed questionnaire was administered to hospitalized patients in the Department of Medical Oncology in Sun Yat-Sen University Cancer Center between 20 September 2014 and 20 September 2015. This study included lymphoma patients who were enrolled into a radical treatment clinical trial, and head/neck cancer patients participating in a palliative clinical trial. Results : There were 136 lymphoma patients and 87 head/neck cancer patients who completed and returned the questionnaire. The questionnaire return rate was 100%. More than 90% of the patients in both groups showed trust and acceptance for medical care personnel, and more than 50% of the patients in both groups were in hope of trying new medication, receiving free medication, and receiving new treatment at an earlier rate. As compared with those in the radical trials, patients in the palliative clinical trials were more likely to hope to try new medication ( P <0.001) and receive a new treatment at an earlier date ( P =0.025), but less likely to hope to receive free medication ( P =0.047). Conclusions : This study reveals several shared perceptions and needs of patients in both the radical (lymphoma) and palliative (head/neck cancer) settings and explores the differences in patients' attitudes between radical clinical trials and palliative clinical trials. These findings may provide a basis for improving recruitment of patients for different types of clinical trials and ensuring that patients have a better understanding of clinical trials., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Five new aromatic compounds, designed as lucidumins A-D (1-4) and lucidimine E (9), along with seven known aromatic compounds (5-8, 10-12) were isolated from Ganoderma lucidum. Their structures were determined by spectroscopic method. Bioactive evaluation showed that compounds 2-4 and 6-10 displayed remarkable neuroprotective activities against corticosterone-induced PC12 cell damage, with the cell viability ranging from 69.99% to 126.00%; and compounds 1-4, 9 and 10 exhibited significant anti-inflammatory activities against LPS-induced nitric oxide (NO) production in RAW264.7 macrophages, with IC 50 values ranging from 4.68 to 15.49 μM. In particular, compound 10 showed remarkable neuroprotection with EC 50 value of 2.49 ± 0.12 μM, and potent anti-inflammation with IC 50 value of 4.68 ± 0.09 μM., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aim: To discuss the effects and mechanism of microRNA-34a in cell apoptosis induced by osteoarthritis., Methods: Collection of the normal and osteoarthritis synovial tissues and measurements of the miRNA-34a and TGIF2 gene expression. In the cell experiment, the cells were divided into Control, Blank and miRNA inhibitor group. The cell proliferation and apoptosis of the different groups were measured by MTT and flow cytometry and the TGIF2 protein expression in the different groups was evaluated by WB assay. The correlation between TGIF2 and miRNA-34a was analyzed by Double luciferase experiment., Results: Compared with normal synovial tissues, the miRNA-34a gene expression was significantly up-regulated and TGIF2 gene expression was significantly suppressed in osteoarthritis synovial tissues (p < 0.001, respectively). The cell proliferation was significantly depressed and the cell apoptosis rate was significantly increased in miRNA inhibitor group compared with the Control group (p < 0.001, respectively). Using the WB assay it was shown that the TGIF2 protein expression of miRNA inhibitor group was significantly suppressed compared with that of Control group (p < 0.01). By Double luciferase assay, TGIF2 gene was one target gene of miRNA-34a., Conclusion: miRNA-34a could induce osteoarthritis synovial cell apoptosis via regulation of TGIF2 in vitro (Fig. 6, Ref. 29).

Four new dihydrophenanthrenofuran, bleochranols A-D (1-4), along with 21 known compounds including phenanthrenes (5-14) and bibenzyls (15-25) were isolated and elucidated from the rhizomes of Bletilla ochracea. Combination of 1D/2D NMR techniques and the Electronic Circular Dichroism (ECD) spectroscopy based on the empirical helicity rules, chemical structure of those isolates were determined. All the compounds were evaluated for cytotoxicity against HL-60, SMMC-7721, A-549, MCF-7 and SW480 human cancer cell lines by MTS assay and anti-inflammatory activity by nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages. Among the 25 tested compounds, bleochranol A (1) showed remarkable cytotoxic activity against HL-60, A-549, and MCF-7 with IC 50 values of 0.24 ± 0.03, 3.51 ± 0.09 and 3.30 ± 0.99 μM respectively. The anti-inflammatory assay showed that compound 12 exhibited most potential activity against NO production in RAW 264.7 macrophages with IC 50 2.86 ± 0.17 μM. The results indicated that the main chemical constituents of B. ochracea were phenanthrene and bibenzyl and similar to that of B. striata., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Chronic obstructive pulmonary disease (COPD) is one of the most common comorbidities in community acquired pneumonia (CAP) patients. We aimed to investigate the characteristics and mortality risk factors of COPD patients hospitalized with CAP., Methods: A retrospective cohort study was conducted at Shanghai Pulmonary Hospital and Shanghai Dahua Hospital. Clinical and demographic data in patients diagnosed with CAP were collected between January 2015 and June 2016. Logistic regression analysis was performed to screen mortality risk factors of COPD patients hospitalized with CAP., Results: Of the total 520 CAP patients, 230 (44.2%) patients had been diagnosed comorbid with COPD (COPD-CAP). CAP patients comorbid with COPD patients had higher rate of need for ICU admission (18.3% vs 13.1%) and need for NIMV (26.1% vs 1.4%) than without COPD (nCOPD-CAP). The PSI, CURB-65 and APACHE-II scores in COPD-CAP patients were higher than that in nCOPD-CAP patients (95 vs 79, P < 0.001; 1 vs 1, P < 0.001; 13 vs 8, P < 0.001, respectively). Logistic regression analysis indicated that aspiration, D-dimer > 2.0 μg/mL and CURB-65 ≥ 3 were risk factors associated with in-hospital mortality ((odd ratio) OR = 5.678, OR = 4.268, OR = 20.764, respectively) in COPD-CAP patients. The risk factors associated with 60-day mortality in COPD-CAP patients were comorbid with coronary heart disease, aspiration, need for NIMV (non-invasive mechanical ventilation) and CURB-65 ≥ 3 (OR = 5.206, OR = 7.921, OR = 3.974, OR = 18.002, respectively)., Conclusions: COPD patients hospitalized with CAP had higher rate of need for NIMV, need for ICU admission and severity scores than those without COPD. Aspiration, D-dimer > 2.0 μg/mL, comorbid with coronary heart disease, need for NIMV and CURB-65 ≥ 3 were mortality risk factors in CAP patients comorbid with COPD.

Objective: The aim of this study was to evaluate the effects and mechanism of miRNA-31 in synovial cells apoptosis induced by RA., Methods: The miRNA-31 gene expressions were extracted from synovial tissues of normal and RA patients by RT-PCR and H et E staining. The synovial cells of RA patients were isolated and randomly divided into Control, Blank and miRNA groups. The cell apoptosis of difference groups were measured by flow cytometry; the TNF-α and IL-1β concentrations of difference groups were measured by Elisa assay; TLR4 and NF-κB proteins expressions were measured by WB assay and the correlation between TLR4 and miRNA-31 were evaluated by double luciferase target experiment., Results: The miRNA-31 gene expression was significantly suppressed in RA tissues (p<0.001); Compared with control group, the cell apoptosis rate of miRNA group was significantly suppressed (p<0.001); TNF-α and IL-1β concentrations were significantly down-regulation in culture fluid (p<0.001, respectively) and TLR4 and NF-κB proteins expressions were significantly depressed (p<0.001, respectively) in miRNA group. By double luciferase target experiment, the TLR4 was a target gene of miRNA-31., Conclusion: miRNA-31 is a key role in synovial cells apoptosis induced by RA (Fig. 7, Ref. 23).

Opioid analgesics remain the first choice for the treatment of moderate to severe pain, but they are also notorious for their respiratory depression and addictive effects. This study focused on the pharmacology of a novel opioid receptor mixed agonist DPI-125 and attempted to elucidate the relationship between the δ-, μ- and κ-receptor potency ratio and respiratory depression and abuse liability. Five diarylmethylpiperazine compounds (DPI-125, DPI-3290, DPI-130, KUST202 and KUST13T02) were selected for this study. PKA fluorescence redistribution assays in CHO cells individually expressing δ-, μ- or κ-receptors were used to measure the agonist potency. The respiratory safety profiles were estimated in rats by the ratio of ED 50 (pCO 2 increase)/ED 50 (antinociception). The abuse liability of DPI-125 was evaluated with a self-administration model in rhesus monkeys. The observed agonist potencies of DPI-125 for δ-, μ- and κ-opioid receptors were 4.29±0.36, 11.10±3.04, and 16.57±4.14 nmol/L, respectively. The other four compounds were also mixed agonists with varying potencies. DPI-125 exhibited a high respiratory safety profile, clearly related to its high δ-receptor potency. The ratio of the EC 50 potencies for the μ- and δ-receptors was found to be positively correlated with the respiratory safety ratio. DPI-125 has similar potencies for μ- and κ-receptors, which is likely the reason for its reduced abuse potential. Our results demonstrate that the opioid receptor mixed agonist DPI-125 is safer and less addictive than traditional μ-agonist analgesics. These findings suggest that the development of δ>μ∼κ opioid receptor mixed agonists is feasible, and such compounds could represent a promising class of potent analgesics with wider therapeutic windows.

To study effects of cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein (c-FLIP) inhibition by RNA interference (RNAi) on sensitivity of U2OS cells to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced apoptosis, plasmid pSUPER-c-FLIP-siRNA was constructed and then transfected into U2OS cells. A stable transfection cell clone U2OS/pSUPER-c-FLIP-siRNA was screened from the c-FLIP-siRNA transfected cells. RT-PCR and Western blotting were applied to measure the expression of c-FLIP at the levels of mRNA and protein. The results indicated that the expression of c-FLIP was significantly suppressed by the c-FLIP-siRNA in the cloned U2OS/pSUPER-c-FLIP-siRNA as compared with the control cells of U2OS/pSUPER. The cloned cell line of U2OS/pSUPER-c-FLIP-siRNA was further examined for TRAIL- induced cell death and apoptosis in the presence of a pan-antagonist of inhibitor of apoptosis proteins (IAPs) AT406, with or without 4 hrs pretreatment with rocaglamide, an inhibitor of c-FLIP biosynthesis, for 24 hrs. Cell death effects and apoptosis were measured by the methods of MTT assay with 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide and flow cytometry, respectively. The results indicated that TRAIL-induced cell death in U2OS/pSUPER-c-FLIP-siRNA was increased compared with control cells U2OS/pSUPER in the presence or absence of AT406. Flow cytometry indicated that TRAIL-induced cell death effects proceeded through cell apoptosis pathway. However, in the presence of rocaglamide, cell death or apoptotic effects of TRAIL were similar and profound in both cell lines, suggesting that the mechanism of action for both c-FLIP-siRNA and rocaglamide was identical. We conclude that the inhibition of c-FLIP by either c-FLIP-siRNA or rocaglamide can enhance the sensitivity of U2OS to TRAIL-induced apopotosis, suggesting that inhibition of c-FLIP is a good target for anti-cancer therapy.

Purpose: To explore the risk factors for falls in lymphoma patients receiving chemotherapy., Methods: Lymphoma patients (203) who received chemotherapy were prospectively recruited and analyzed. Eligible participants were followed up by weekly telephone contact for 6 months or until the time of a fall or death. Risk factors for falling in lymphoma patients were identified using univariate regression analysis and multivariate binary logistic regression analysis., Results: Of the 203 cases, 13.3% (27 cases) had a fall during follow-up. Univariate regression analysis showed the following risk factors for falls in lymphoma patients: gender (P = 0.023), Eastern Cooperative Oncology Group (ECOG) performance status score (P < 0.0001), cancer stage (P < 0.0001), extranodal involvement (P = 0.041), serum lactate dehydrogenase (LDH) level (P < 0.0001), revised International Prognostic Index (R-IPI) (P < 0.0001), history of falls (P < 0.0001), gait (P < 0.0001), cognitive condition (P = 0.029) and intravenous catheter placement (P < 0.0001). Multivariate binary logistic regression analysis found four independent factors significantly associated with the risk of falling in lymphoma patients: female gender (P = 0.042), later stage (P = 0.021), R-IPI (P = 0.030), and intravenous catheter placement (P = 0.001)., Conclusions: Gender, stage, R-IPI, and intravenous catheter placement were independent risk factors for falls in patients with lymphoma. Lymphoma patients with these four risk factors should receive particular attention and fall prevention education to reduce the incidence of falls. The R-IPI may be a new predictor of falling in lymphoma patients and may aid in the management of falls., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: To study the effect of problem-based learning(PBL) and case-based study(CBS) for knowledge acquisition and clinical performance in the practice teaching of clinical prosthodontics courses., Methods: Consecutive cohorts of year 2 clinical students taught using a traditional prosthodontics curriculum (students who practiced in Xuzhou Stomatological Hospital from June 2007 to June 2008, n=30) and a PBL and CBS curriculum (who practiced in Xuzhou Stomatology hospital from June 2008 to June 2009, n=30) were compared.Students completed an end-of-attachment examination and a questionnaire in which students were requested to rate themselves on 7 competencies. The data was analyzed with CS10.34 software package., Results: The PBL and CBS curriculum resulted in significantly better examination performance than did the traditional teaching curriculum (P<0.05). The excellent rate was 46.7% in the PBL and CBS curriculum while 23.3% in the traditional teaching curriculum. It was found that most students considered PBL and CBS useful for them., Conclusions: Examination performance indicates that the PBL and CBS curriculum is more successful than the previous course. PBL and CBS can be used to stimulate and underpin the acquisition of knowledge, skill and attitudes, and is worthy of generalization in clinical prosthodontics courses.

Objective: To estimate the biological exposure limit (BEL) using benchmark dose (BMD) based on two sets of data from occupational epidemiology., Methods: Cadmium-exposed workers were selected from a cadmium smelting factory and a zinc product factory. Doctors, nurses or shop assistants living in the same area served as a control group. Urinary cadmium (UCd) was used as an exposure biomarker and urinary beta2-microgloburin (B2M), N-acetyl-13-D-glucosaminidase (NAG) and albumin (ALB) as effect biomarkers. All urine parameters were adjusted by urinary creatinine. Software of BMDS (Version 1.3.2, EPA.U.S.A) was used to calculate BMD., Results: The cut-off point (abnormal values) was determined based on the upper limit of 95% of effect biomarkers in control group. There was a significant dose response relationship between the effect biomarkers (urinary B2M, NAG; and ALB) and exposure biomarker (UCd). BEL value was 5 microg/g creatinine for UB2M as an effect biomarker, consistent with the recommendation of WHO. BEL could be estimated by using the method of BMD. BEL value was 3 microg/g creatinine for UNAG as an effect biomarker. The more sensitive the used biomarker is, the more occupational population will be protected., Conclusion: BMD can be used in estimating the biological exposure limit (BEL). UNAG is a sensitive biomarker for estimating BEL after cadmium exposure.

This article introduces cryosurgery devices, cryopreservation devices, some cryogenic freezing methods in medicine and the recent progress about cryotherapy technology.

Objective: Based on two sets of data from occupational epidemiology, Benchmark dose (BMD) was applied to estimate biological exposure limit (BEL)., Methods: Cadmium exposed workers were selected from a cadmium smelting and a zinc products factory and control group was selected from doctors or nurses and staff from shops living in the same area; Urinary cadmium (UCd) was used as exposure biomarker and urinary beta(2) microglobulin (UBM), NAG (UNAG) and albumin (UALB) were as effect biomarkers. All urine parameters were adjusted by urinary creatinine. Software of BMDS (Version 1.3.2, EPA.U.S) was used to calculate BMD., Results: Calculated abnormal prevalence was based on the upper limit of 95% of effect biomarkers in control group; There are significant dose response relationship between the prevalence of effect biomarkers (UBM, UNAG and UALB) and exposure biomarker (UCd); BEL was 5 microg/g creatinine for UBM as effect biomarker, It consists with the recommendation of WHO; BEL was 3 microg/g creatinine for UNAG as effect biomarker; BEL can be estimated by using the method of BMD; the more sensitive biomarker would used, the more occupational people would protected., Conclusion: The application of BMD in estimating biological exposure limit (BEL) is proper. UNAG is suggested as most sensitive biomarker to be used to estimate BEL for cadmium exposure.

Objective: To estimate the benchmark dose for osteoporosis caused by cadmium exposure in a Chinese general population with an epidemiological study., Methods: The inhabitants living in both cadmium polluted and non-polluted areas served as the exposure group and the control group. Urinary cadmium (UCd) and Blood cadmium (BCd) were used as exposure biomarkers while the Z score was used as effect biomarker for the osteoporosis., Results: The UCd and BCd in the habitants of the polluted areas were significantly higher than those in the habitants of the control area on average (P < 0.05) and the UCd and BCd in the habitants of the highly polluted areas were significantly higher than those in the habitants of the moderately polluted area on average (P < 0.05). The bone mineral density was significantly decreased in the groups of the highest UCd and BCd level compared with the 5 microg/g Cr group with the significant difference (P < 0.05). The morbidity of the osteoporosis would increase significantly with the increase of the cadmium exposure (P < 0.05) with the linear correlation (P < 0.05). BMDs were calculated using BMDS Version l.3.2 software and BMDLs were also determined. The BMDL of UCd for cadmium-induced osteoporosis was higher than those representing cadmium-induced renal dysfunction., Conclusion: High level of cadmium exposure can induce osteoporosis, which occurs later than renal damage related to cadmium exposure. The BMD is a practical method.

Using 20% DMSO and 6% propylene glycol in Kreb' Ringer phosphate solution as cryopotective agent for homograft vitrification storage, the viability of stored homograft (79.2%) was higher than that of slow cooling storage (59.7%). About 540000 cm2 of vitrified homograft were used to cover the wounds after excision of burn eschar in 135 patients with major burns. The take-rate was over 94%. The cryopreservation of skin by vitrification can improve the viability and quality of skin and save time and cost.

A gas chromatographic method for the determination of mexiletine in human plasma is described. Mexiletine was simultaneously extracted and derivatized with carbon disulphide for separation and quantitation on a glass column (1.5 m x 3 mm i.d.) packed with 1.5% OV-1 coated on 80-100 mesh Shimalite W (201D). The method required only 0.5 mL of plasma and could detect as little as 10 ng of mexiletine. It has been applied to the study of the pharmacokinetics of mexiletine in healthy volunteers.