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Fourteen undescribed seco-type diterpenoids, named nudifloids A-N, together with ten known analogs, were isolated from the leaves of Callicarpa nudiflora. Nudifloids A-N had a characteristic 3,4-seco-labdane-type diterpenoid skeleton, whereas nudifloids A-C and K-N were 3,4-seco-norditerpenoids. Nudifloid A was the first example of a 3,4-seco-12,13,14,15,16-quartnor-labdane diterpenoid, with a seven-membered lactone ring formed through esterification between C-3 and C-11. Nudifloids B and C were a pair of highly modified 3,4-seco-labdane nor-diterpenoid epimers, of which C-2 and C-18 were cyclized together to form a cyclohexene fragment. The structures of these undescribed diterpenoids were established by spectroscopic analysis and reference data. The anti-inflammatory activity of diterpenoids in rich yield was evaluated by analyzing the inhibition of lipopolysaccharide plus nigericin-induced pyroptosis in J774A.1 cells. Nudifloids D and E exhibited prominent anti-NLRP3 inflammasome activity, with IC 50 values of 1.80 and 1.59 μM, respectively. Cell permeability assays revealed that nudifloid D inhibited pyroptosis, which could ameliorate inflammation by blocking the activation of the NLRP3 inflammasome., 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 Ltd. All rights reserved.)

A spiro ent -clerodane homodimer with a rare 6/6/6/6/6-fused pentacyclic scaffold, spiroarborin ( 1 ), together with four new monomeric analogues ( 2 - 5 ), were isolated from Callicarpa arborea . Their structures were elucidated by comprehensive spectroscopic data analysis, quantum-chemical calculations, and X-ray diffraction. A plausible biosynthetic pathway of 1 was proposed, and a biomimetic synthesis of its derivative was accomplished. Compound 1 showed a potent inhibitory effect by directly binding to the YEATS domain of the 11-19 leukemia (ENL) protein with an IC 50 value of 7.3 μM. This gave a K D value of 5.0 μM, as recorded by a surface plasmon resonance binding assay.

Extremely low-frequency electromagnetic field (ELF-EMF) exposures influence many biological systems. These effects are mainly related to the intensity, duration, frequency, and pattern of the ELF-EMF. Our intent was to characterize the effect of specific pulsed electromagnetic fields on the in vitro proliferation of MCF-7 adenocarcinoma and MDA-MB-231 breast cancer cell lines and one non-cancerous M10 breast epithelial cell line. The following four important parameters of ELF-EMF were examined: frequencies (7.83 ± 0.3, 23.49 ± 0.3, and 39.15 ± 0.3 Hz), flux density (0.5 and 1 mT), exposure duration (12, 24, and 48 h), and the exposure methodology (continuous exposure versus switching exposure). The viability of MDA-MB-231 cells exposed to the optimized ELF-EMF pattern (7.83 ± 0.3 Hz, 1 mT, and 6 h switching exposure) was 40.1%. By contrast, the optimized ELF-EMF parameters that were most cytotoxic to breast cancer MDA-MB-231 cells were not damaging to normal M10 cells. In vitro studies also showed that exposure of MDA-MB-231 cells to the optimized ELF-EMF pattern promoted Ca 2+ influx and resulted in apoptosis. These data confirm that exposure to this specific ELF-EMF pattern can influence cellular processes and inhibit cancer cell growth. The specific ELF-EMF pattern determined in this study may provide a potential anti-cancer treatment in the future.

As a successful anti-tumor drug target, the family of histone deacetylases (HDACs) is also a critical player in immune response, making the research of anti-inflammatory HDAC inhibitors an attractive new focus. In this report, triterpenoids nigranoic acid (NA) and manwuweizic acid (MA) were identified as HDAC inhibitors through docking-based virtual screening and enzymatic activity assay. A series of derivatives of NA and MA were synthesized and assessed for their biological effects. As a result, hydroxamic acid derivatives of NA and MA showed moderately increased activity for HDAC1/2/4/6 inhibition (the lowest IC 50 against HDAC1 is 1.14 μM), with no activity against HDAC8. In J774A.1 macrophage, compound 1-3, 13 and 17-19 demonstrated inhibitory activity against lactate dehydrogenase (LDH) and IL-1β production, without affecting cell viability. Compound 19 increased the histone acetylation level in J774A.1 cells, as well as inhibited IL-1β maturation and caspase-1 cleavage. These results indicated that compound 19 blocks the activation of NLRP3 inflammasome, probably related to HDAC inhibition. This work provided a natural scaffold for developing low-cytotoxic and anti-inflammatory HDAC inhibitors, as well as a class of tool molecules for studying the relationship between HDACs and NLRP3 activation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

In order to discover and develop the new HIV-1 NNRTIs, a series of 5-alkyl-6-(benzo[d][1,3]dioxol-5-ylalkyl)-2-mercaptopyrimidin-4(3H)-ones was synthesized and screened for their in vitro cytotoxicity against HIV-1. Most of the compounds we synthetized showed high activity against wild-type HIV-1 strain (IIIB) while IC 50 values are in the range of 0.06-12.95 μM. Among them, the most active HIV-1 inhibitor was compound 6-(benzo[d][1,3]dioxol-5-ylmethyl)-5-ethyl-2-((2-(4-hydroxyphenyl)-2-oxoethyl)thio)pyrimidin-4(3H)-one (5b), which exhibited similar HIV-1 inhibitory potency (IC 50  = 0.06 μM, CC 50  = 96.23 μM) compared with nevirapine (IC 50  = 0.04 μM, CC 50 >200 μM) and most of compounds exhibited submicromolar IC 50 values indicating they were specific RT inhibitors. The compounds 5b, 6-(benzo[d] [1,3]dioxol-5-yl)-5-ethyl-2-((2-(4-hydroxyphenyl)-2-oxoethyl)thio)pyrimidin-4(3H)-one (5c) and 4-(2-((4-(benzo[d][1,3]dioxol-5-ylmethyl)-5-ethyl-6-oxo-1,6-dihydropyrimidin-2-yl)thio)acetyl)phenylbenzo[d][1,3]dioxole-5-carboxylate (5r) were selected for further study. It was found that all of them had little toxicity to peripheral blood mononuclear cell (PBMC), and had a good inhibitory effect on the replication of HIV-1 protease inhibitor resistant strains, fusion inhibitor resistant strains and nucleosides reverse transcriptase inhibitor resistant strains, as well as on clinical isolates. Besides, compound 5b and 5c showed inhibition of HIV-1 RT RNA-dependent DNA polymerization activity and DNA-dependent DNA polymerization activity, while compound 5r only showed inhibition of HIV DNA-dependent DNA polymerization activity, which was different from classical reverse transcriptase inhibitors. Our study which offered the preliminary structure-activity relationships and modeling studies of these new compounds has provided the valuable avenues for future molecular optimization., 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 Inc. All rights reserved.)

During the past 100 years, there had been four global pandemics on influenza that had greatly influenced the health and life of the people. This article summarized the features, experiences and lessons learned on these four influenza pandemics so as to prepare related measures targeting the possible pandemics/epidemics in the foreseeable future, in China.

Objective: To describe the epidemic of imported infectious diseases in China between 2013 and 2016, including the kinds of infectious diseases, affected provinces, source countries and the epidemiological characteristics, and provide scientific information for the prevention and control of imported infectious diseases. Methods: Data of cases of imported infectious diseases in China from 2013 to 2016 were collected from national information reporting system of infectious diseases, Microsoft Excel 2010 and SPSS 18.0 were used to conduct data cleaning and analysis. Results: From 2013 to 2016, a total of 16 206 imported cases of infectious diseases were reported in China. Of all the cases, 83.12% (13 471 cases) were malaria cases, followed by dengue fever (2 628 cases, 16.22%). The majority of the imported cases were males (14 522 cases, 89.61%). Most cases were aged 20-50 years. Except Zika virus disease and yellow fever, which were mainly reported before and after spring festival, other imported infectious diseases mainly occurred in summer and autumn. The epidemic in affected provinces varied with the types of infectious diseases, and Yunnan reported the largest case number of imported infectious diseases, followed by Jiangsu, Guangxi and Guangdong. The imported cases were mainly from Asian countries, such as Burma, and African countries, such as Angola, Equatorial Guinea and Ghana, which also varied with the types of infectious diseases. Conclusions: We should pay more attention to imported infectious diseases and strengthen the prevention and control measures in our country. In order to reduce the incidence of imported infectious diseases, the health education should be enforced for persons who plan to travel abroad and the active surveillance should be strengthened for returned travelers.

Background: The Ebola virus disease spread rapidly in West Africa in 2014, leading to the loss of thousands of lives. Community engagement was one of the key strategies to interrupt Ebola transmission, and practical community level measures needed to be explored in the field and tailored to the specific context of communities., Methods: First, community-level education on Ebola virus disease (EVD) prevention was launched for the community's social mobilizers in six districts in Sierra Leone beginning in November 2014. Then, from January to May of 2015, in three pilot communities, local trained community members were organized to engage in implementation of EVD prevention and transmission interruption measures, by involving them in alert case report, contact tracing, and social mobilization. The epidemiological indicators of transmission interruption in three study communities were evaluated., Results: A total of 6 016 community social mobilizers from 185 wards were trained by holding 279 workshops in the six districts, and EVD message reached an estimated 631 680 residents. In three pilot communities, 72 EVD alert cases were reported, with 70.8 % of them detected by trained local community members, and 14 EVD cases were finally identified. Contact tracing detected 64.3 % of EVD cases. The median duration of community infectivity for the cases was 1 day. The secondary attack rate was 4.2 %, and no third generation of infection was triggered. No health worker was infected, and no unsafe burial and noncompliance to EVD control measures were recorded. The community-based measures were modeled to reduce 77 EVD cases, and the EVD-free goal was achieved four months earlier in study communities than whole country of Sierra Leone., Conclusions: The community-based strategy of social mobilization and community engagement was effective in case detection and reducing the extent of Ebola transmission in a country with weak health system. The successfully practical experience to reduce the risk of Ebola transmission in the community with poor resources would potentially be helpful for the global community to fight against the EVD and the other diseases in the future.

Objective: To compare the different surveillance system evaluation guidelines proposed by US Center for Disease Control and Prevention (CDC) and WHO, so as to develop an evaluation strategy suitable for communicable disease surveillance systems in China., Methods: Systematic collection and review on the guidelines that were proposed by US CDC and WHO. Situation analysis together with feasibility analysis were linked to the analysis of evaluation strategy used in China., Results: US CDC guidelines were more appropriate for evaluating those single or simple systems that focusing on those 'system characteristics' while the. WHO protocols were more appropriate for evaluating the multi-system or complicated system which focusing on data related to 'system functions'. The US CDC guidelines had been widely used in China and it was the right moment to start to evaluate the functions., Conclusion: More flexible and comprehensive strategy based on national conditions is needed when constitute the national communicable disease surveillance evaluation guidelines. The multi-step strategy described in this article could be used as reference.

Objective: To analyze the timeliness of detection and reporting on public health emergency events, and to explore the effective strategies for improving the relative capacity on those issues., Methods: We conducted a retrospective survey on 3275 emergency events reported through Public Health Emergency Events Surveillance System from 2005 to the first half of 2006. Developed by county Centers for Disease Control and Prevention, a uniformed self-administrated questionnaire was used to collect data, which would include information on the detection, reporting of the events., Results: For communicable diseases events, the median of time interval between the occurrence of first case and the detection of event was 6 days (P25 = 2, P75 = 13). For food poisoning events and clusters of disease with unknown origin, the medians were 3 hours (P25, P75 = 16) and 1 days (P25 = 0, P75 = 5). 71.54% of the events were reported by the discoverers within 2 hours after the detection., Conclusion: In general, the ranges of time intervals between the occurrence, detection or reporting of the events were different, according to the categories of events. The timeliness of detection and reporting of events could have been improved dramatically if the definition of events, according to their characteristics, had been more reasonable and accessible, as well as the improvement of training program for healthcare staff and teachers.

Objective: To describe the occupational distribution of staff who worked on detection and reporting on public health emergency events, and to explore the effective strategies for identification and reporting on emergency events., Methods: We conducted a retrospective survey on 3275 emergent events reported through Public Health Emergency Events Surveillance System from 2005 to the first half of 2006. Data were collected by uniform self-administrated questionnaires by county Centers for Disease Control and Prevention, including information on events detection and reporting, etc., Results: Among event discoverers, 56.40% (1847/3275) were healthcare staff, 20.58% (674/3275) were teachers, and 15.15% (496/3275) were staff from the disease control systems. Among those event reporters, 56.82% (1861/3275) were healthcare staff, 21.77% (713/3275) from disease control system and 10.75% (352/ 3275) were teachers., Conclusion: Healthcare staff and teachers played the most important role in detection and reporting on events. It would be favorable to improve the ability of events detection and reporting if we could enhance the training program to the relative staff in medical facilities and school settings especially at the grass root level.

Background: To find the pathogenic agents of aseptic meningitis prevalent in Xuzhou of Jiangsu province in 2001., Methods: The enterovirus (EV) was cultured from CSF of the patients and identified with anti-serum by neutralization test. Neutralization titer of antibody in paired sera from meningitis children was determined. EV RNA was detected by RT-PCR., Results: Four strains of Coxsackievirus B5, 2 strains of Coxsackievirus B3 and 1 strain of Echovirus 7 were isolated from 22 CSF specimens. The isolation rate of virus was 31.8% (7/22), 21 CSF were tested by RT-PCR, the positive rate of EV RNA was 52.4% (11/21); 57.9% (11/19) of patients paired-sera had over 4 folds antibody rise or became seroconverted., Conclusion: Enterovirus was the pathogenic agent of aseptic meningitis prevalent in Xuzhou of Jiangsu province, the main serotype of the virus was Coxsackievirus B5.

Objective: To carry out epidemiological study on an outbreak caused by E. coli O157:H7 infection in Jiangsu province in 1999., Methods: Epidemiological, microbiological and moleculebiological methods were used to find out the source, route of transmission and risk factors., Results: 95 severe O157:H7 infected patients with acute renal failure in 9 counties and districts of 2 municipalities were reported in Jiangsu province, 1999 while 83 of the patients died with a death rate of 87.37%. Most patients were seen in mid or late June. The ratio of male to female was 1 to 1.44 and 88.42% of the patients were over 50 years old. 38 patients occurred in 2000 with 34 deaths. Major factors contributing to the outbreak would include without drinking tap water, eating leftover food, poor sanitary status in kitchen, not washing hands before meal and after bowl movement. 2 strain of O157:H7 was isolated from severe patients and 3 from diarrhea cases. Carrier rate among animals was up to 9.62% and 99.41% of the strains carried toxic gene. Strains isolated from feces of patients and animals belonged to the same colonies., Conclusion: This outbreak was severe which caused by O157:H7 and was first seen in China, which was closely related to the high carrier rate of O157:H7 in animals and to the positive rate of high toxic gene of the strains. There were various routes of transmission and the main factors of infection would include poor personal health habits and poor sanitation of the household.

Objective: To estimate the frequency of injections and proportion of unsafe injections and to analyses the critical determinants of poor injection practices in general population in China. Also, to study knowledge, attitudes, practice research in providers and general population., Methods: A random sample consisting residents and health care providers in a rural county was elected and interview about the frequency of received injection, as well as knowledge, attitudes and practices regarding injections were studied., Results: Overall, 1 004 village residents, and 94 providers were interviewed. Among residents, 145 persons (14.4%), with 457 times (0.46 times per person) had received at least one injection during the previous 3 months. The frequency of injection was 1.84 per year. The proportion of received injections on treatment and immunizations was significantly different among > 12 years age group and < or = 12 years age group. Ninety-four point four percent of disposable syringes/needles were used for injections. Knowledge among the population and providers regarding injection safety was limited., Conclusion: Injections were moderately frequent in this rural area and the proportions of disposable syringes/needles used for injections was very high. Knowledge of safe injection and reasonable injection as well as consciousness of self-protection in the providers and residents need to be improved.