We designed and synthesized eighteen lycorine derivatives with five different structural types, and evaluated their antiviral activities on a HCoV-OC43-infected H460 cell model. Structure-activity relationships suggested that the introduction of appropriate substituents on the 6N atom of lycorine was beneficial to activity. Compound 6a gave a good activity with the half effective concentration (EC₅₀) and selectivity index (SI) values of 2.36 μmol·L^-1 and 16.52, respectively. Surface plasmon resonance (SPR) result indicated that 6a might target the non-structural protein 12 (NSP12) subunit in RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 with the dissociation constant (K_D) value of 1.36 μmol·L^-1. Molecular docking indicated that 6a might act on nidovirus RdRp-associated nucleotidyltransferase (NiRAN) catalytic center of NSP12, distinct from the mechanism of nucleoside-like drugs such as remdesivir. This study provides scientific data for the development of lycorine derivatives into a new class of anti-SARS-CoV-2 small molecule inhibitors.

Background and purpose: Cervical nodal metastasis in nasopharyngeal carcinoma plays an important role in the definition of radiotherapy area and clinical staging, it is also one of the main factors influencing prognosis. So this study was designed to explore the pattern of metastatic lymph nodes for patients with nasopharyngeal carcinoma, which may provide a basis for clinical treatment and research. Methods: From Jun. 2005 to Sep. 2007,779 histologically diagnosed nasopharyngeal carcinoma patients had routine MRI scan before radiation therapy at Fujian Provincial Cancer Hospital. Diagnostic radiologists and radiation oncoiogists together assessed the nodal distribution according to the guideline CT-hased delineation of lymph node levels. Then, Chi-sqnare test was used to analyze the correlation between T stage and nodal metastasis rate and between nodal diameter and nodal extracapsular invasion. Results: Of 779 patients, 592(76.0%) had nodal involvement. The distribution was as follows: 1 in level Ⅰ,384 in level Ⅱa, 499 in level Ⅱ_b, 184 in level Ⅲ, 33 in level Ⅳ, 67 in level V_a, 21 in level V_b, 597 in retropharynx.In these patients, a total of 1 479 postive nodes, including 973 (65.79%) extracapsular spread nodes, were detected.The rate of nodal extracapsular invasion was higher when the axial diameter increased. Leap metastasis rate was 1.0%. No significant correlation was found between T stage and nodal involvement. Conclusion: The level Ⅱ and retropharyngeal node were the most frequently involved regions, they had similar metastatic rate and were both the first echo node to metastases of nasopharyngeal carcinoma. Level Ⅰ metastasis was lower. The proportion of extracapsular spread of metastatic lymph nodes increased with axial diameter of lymph nodes-dependent. The cervical node involvement of nasopharyngeal carcinoma was spread orderly down the neck, and the incidence of skip metastasis is rare. The relationship between T stage and nodal involvement has no statistical significance.

OBJECTIVETo explore the potential effect of Guizhi plus Gegen Decoction (GGD) in improving learning and memory of lipopolysaccharides (LPS) induced neuroinflammatory mice and its possible mechanisms.

METHODSTotally 63 male ICR mice were randomly divided into 5 groups, i.e., the normal control (n = 13), the model group (n = 13), the low dose GGD group (n = 10), the high dose GGD group (n = 14), and the positive control group (n = 13). Mice were intraperitoneally injected with LPS (0.33 mg/kg) to induce Alzheimer's disease (AD) model. Mice in the high and the low dose GGD groups were administered with 12 g/kg or 6 g/kg by gastrogavage for 4 successive weeks. Mice in the control group were intraperitoneally injected with minocycline (50 mg/kg) for 3 days. By the end of treatment LPS were injected 4 h before behavior test each day, and then behavior test was conducted in mice of each group. Effect of GGD on learning and memory of AD mice was observed by using open field test, novel object recognition task, and Morris water maze.

RESULTSOpen field test showed there was no statistical difference in the movement time and the movement distance among all groups (P > 0.05), suggesting that LPS and GGD had no effect on locomotor activities of mice. In novel object recognition test, AD mice spent significantly shorter time to explore novel object after they were induced by LPS (P < 0.05), while for AD mice in the low and high dose GGD groups, their capacities for exploration and memory were significantly improved (P < 0. 05, P < 0.01). Results of Morris water maze showed that AD mice exhibited increased escape latency (P < 0.05) and spent much less time in swimming across the original platform (both P < 0.05). However, AD mice in the low and high dose GGD groups had obvious shortened latency and increased time percentage for swimming (P < 0.05, P < 0.01).

CONCLUSIONGGD possessed certain improvement in learning and memory disorder of LPS induced AD mice.

Alzheimer Disease ; chemically induced ; drug therapy ; psychology ; Animals ; Drugs, Chinese Herbal ; therapeutic use ; Lipopolysaccharides ; adverse effects ; Male ; Memory Disorders ; prevention & control ; Mice ; Mice, Inbred ICR ; Neuritis ; chemically induced ; drug therapy ; psychology ; Phytotherapy

Heroin addicts were treated with acupuncture, Chinese herbs, and acupuncture plus Chinese herbs respectively, their effects were compared with that of Western medicine.The scores of withdrawal symptoms were observed continuously for 20 days. The effect of acupuncture was better than that of Western medicine 48 hours after the withdrawal treatment (P＜ 0.05), and better than that of other three methods 72 hours after the withdrawal treatment, (P ＜ 0.01). Acupuncture, Chinese herbs, and acupuncture plus Chinese herbs have the detoxification effects of varying degrees, in particular acupuncture' effect was the best. But all the therapies could not completely improve the withdrawal symptoms in the first 3 days of treatment, and acupuncture plus Chinese herbs had no synergetic effect in treating withdrawal symptoms.

Aim To observe whether the activation of aldehyde dehydrogenase 2 ( ALDH2 ) can protect a-gainst diabetes induced liver injury in rat model, and analyze the role of JNK pathway in the liver protection induced by activation of ALDH2 . Methods All male SD rats were randomly divided into three groups: nor-mal control group ( Con ) , diabetes group ( DM ) and ethanol + diabetes group ( EtOH + DM ) . After 8 weeks, the fasting blood glucose ( FBG) level, glyco-sylated hemoglobin ( HbA1c) level, serum AST and ALT levels were measured. The changes of hepatic pa-thology were observed by hematoxylin and eosin ( HE) staining method. The protein expressions of ALDH2, JNK and p-JNK in liver tissue were measured. Result Compared with control group, in DM group, the lev-els of FBG and HbA1c, serum AST and ALT levels were increased significantly. The structure of liver mor-phology was destroyed, disarranged and unclear, the hepatocyte was swollen, and a large number of inflam-matory cells were infiltrated. ALDH2 protein expres-sion was decreased, while the expressions of JNK, p-JNK and the ratio of p-JNK/JNK were increased. Com-pared with DM group, in EtOH+DM group, the levels of FBG and HbA1c, serum AST and ALT levels were decreased. The expression of ALDH2 protein was in-creased, accompanying with the decrease of JNK, p-JNK protein expressions and the ratio of p-JNK/JNK. Conclusion Activation of ALDH2 can protect the liv-er against diabetes induced liver damage in rat model, which may be relevant with inhibiting the JNK path-way.

Objective: To investigate the applied feasibility of scaffold with modified PLA (Polymer of lactic acid) in tissue engineering. Methods:First, we adopted salting-in method to prepare porous foam scaffold. Then, we reconstructed tissue engineering skin by epidermal cells and fibroblasts combined with modified PLA. On the 14th day of cell culturing in vitro, we was a control. Results:The arfificial skin is composed of epidermis and dermis and similar to natural skin in appearance. The skin consists of fibroblasts and keratinocytes, which are in various proliferation and differentiation stages. Fibroblasts and keratinocytes distribute on the surface of polymer of lactic acid (PLA) and the number of fibroblast and keratinocyte increase. Conclusion:Dialdehyde starches (DAS) not only improve the function of PLA but also have good effects on cells. Moreover, it does not affect the growth and the metabolism of the cells. So it is feasible to use modified scaffold to construct tissue engineering skin.

OBJECTIVEGas chromatography (GC) was used to investigate the cellular fatty acid (CFA) composition of 141 Acinetobacter baumannii and 32 A. calcoaceticus isolates from different locations in China and to find chemical markers to differentiate these two closely related bacteria.

METHODSWhole cell fatty acid methyl esters (FAMEs) were obtained by saponification, methylation, and extraction for GC analysis, followed by a standardized Microbial Identification System (MIS) analysis.

RESULTSAll A. baumannii and A. calcoaceticus strains contained some major fatty acids, namely, 18:1 ω9c, 16:0, Sum In Feature 3, 12:0, 17:1ω8c, 3-OH-12:0, 17:0, Sum In Feature 2, 2-OH-12:0, and 18:0 compounds. Although most of the total CFAs are similar between A. baumannii and A. calcoaceticus strains, the ratios of two pairs of CFAs, i.e., Sum In Feature 3/18:1 ω9c versus 16:0/18:1 ω9c and Sum In Feature 3/18:1 ω9c versus unknown 12.484/18:1 ω9c fatty acids, could differentiate these two closely related bacteria. A. baumannii could be easily classified into two subgroups by plotting some ratios such as Sum In Feature 3/16:0 versus 17:0 and Sum In Feature 3/2-OH-12:0 versus 17:0 fatty acids.

CONCLUSIONThe ratios of some CFAs could be used as chemical markers to distinguish A. baumannii from A. calcoaceticus.

Acinetobacter baumannii ; classification ; cytology ; metabolism ; Acinetobacter calcoaceticus ; classification ; cytology ; metabolism ; Biomarkers ; metabolism ; Fatty Acids ; metabolism ; Species Specificity

Macrolactins are 24-membered macrolides produced by unidentified marine bacterium, Actinomadura sp. and Bacillus sp., which exhibit both antibacterial and antitumor activities in vitro. The environmental strain X-2 which was isolated from the sediment of the East China Sea produce Macrolatin A, B and O. In this study, a set of degenerate oligonucleotide primers, designed for amplification ketosynthase(KS) domains, had been employed to identify KS gene fragments of the X-2 DNA samples. One 645 bp KS fragment(GenBank accession no. EF486351)had been cloned and used as a probe to screen the genome DNA fosmid library of X-2. Three positive clones were selected and sequenced, Homologous analysis and the function prediction of the obtained PKS gene fragments suggested that macrolactin is the Polyketide Biosynthesis Product of the gene cluster obtained in the environmental strain X-2.

Adolescent ; Adult ; Antiviral Agents ; administration & dosage ; therapeutic use ; Child ; DNA, Viral ; blood ; Drug Therapy, Combination ; Enzyme-Linked Immunosorbent Assay ; Female ; Follow-Up Studies ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; drug effects ; Hepatitis B, Chronic ; blood ; drug therapy ; virology ; Humans ; Interferon-alpha ; administration & dosage ; therapeutic use ; Lamivudine ; administration & dosage ; therapeutic use ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Young Adult

The chemical constituents of Rhodiola kirilowii were separated and purified by repeated column chromatography on silica gel, RP - 18, Sephadex LH -20 and semi-preparative HPLC. Each compound was characterized by spectroscopic and physical data. Twelve compounds have been purified and identified to be beta-sitosterol (1), tyrosol (2), trans-hydroxycinnamic acid (3), geranyl beta-glucopyranoside (4), neryl beta-glucopyranoside (5), hexyl beta-glucopyranoside (6), gallic acid (7), (-) -epigallocatechin gallate (8), rhodiolgin (9), isolariciresinol-9-O-beta-glucopyranoside (10), rhodiooctanoside (11), and sacranoside B (12). Among them, compounds 3, 6, 9-12 were isolated from Rhodiola kirilowii for the first time; Compounds 4 and 5 were obtained for the first time from the genus Rhodiola. The in vitro activities against Macobacterium tuberculosis (ATCC 27294) of its extracts and pure components were evaluated by testing their MIC (minimal inhibitory concentration) and MBC (minimal bactericidal concentration). The 80% (a. q.) EtOH extract, EtOAc-soluble extract, compounds 7 and 8 exhibited in-vitro inhibitory and bactericidal activities against Macobacterium tuberculosis in different extent.
Antitubercular Agents ; isolation & purification ; pharmacology ; Magnetic Resonance Spectroscopy ; Mass Spectrometry ; Microbial Sensitivity Tests ; Mycobacterium tuberculosis ; drug effects ; Plant Roots ; chemistry ; Rhodiola ; chemistry