Sesquiterpenoids from the whole plants of Elephantopus mollis with cytotoxicity activities.

Five new sesquiterpenoids (1-5), elephantmollides A-E, along with four known compounds (6-9), were isolated from the whole plants of E. mollis. Their planar structures were elucidated using the spectroscopic methods, including HRESIMS, IR, UV, and NMR (1H, 13C, DEPT, HSQC, HMBC, 1H-1H COSY). The relative configurations of them were partially deduced by the NOESY experiment, and the absolute configurations were assigned by comparing the calculated electronic circular dichroism (ECD) results with the experimental data. In addition, cytotoxic activities of 1-9 against HepG2 cells ware tested, and compounds 1-9 exhibited cytotoxic activities with IC50 values ranging from 6.7 to 25.8 µM.

Lycopodium Alkaloids from Huperzia serrata and Their Anti-acetylcholinesterase Activities.

One new fawcettimine-type alkaloid (1), one new miscellaneous-type alkaloid (2), four new lycodine-type alkaloids (3-6), and eight known ones (7-14) were isolated from the whole plants of Huperzia serrata. Their structures and absolute configurations were elucidated based on spectroscopic data, X-ray diffraction, ECD calculation and Mosher's method. Compound 1 was a rare C18 N2 -type Lycopodium alkaloid, possessing serratinine skeleton with an amide side chain in C-5. The absolute configuration of the 18-OH of compounds 4-6 were first determined by Mosher's method. Moreover, compounds 1-14 were assayed anti-acetylcholinesterase effect in vitro, and compound 7 showed significant anti-acetylcholinesterase activity with an IC50 value of 16.18±1.64 µM.

Protective Effect of Inactivated COVID-19 Vaccines against Omicron BA.2 Infection in Guangzhou: A Test-Negative Case-Control Real-World Study.

This study aims to explore the relationship between the doses of inactivated COVID-19 vaccines received and SARS-CoV-2 Omicron infection in the real-world setting, so as to preliminarily evaluate the protective effect induced by COVID-19 vaccination. We conducted a test-negative case-control study and recruited the test-positive cases and test-negative controls in the outbreak caused by Omicron BA.2 in April 2022 in Guangzhou, China. All the participants were 3 years and older. The vaccination status between the case group and the control group was compared in the vaccinated and all participants, respectively, to estimate the immune protection of inactivated COVID-19 vaccines. After adjusting for sex and age, compared with a mere single dose, full vaccination of inactivated COVID-19 vaccines (OR = 0.191, 95% CI: 0.050 to 0.727) and booster vaccination (OR = 0.091, 95% CI: 0.011 to 0.727) had a more superior protective effect. Compared with one dose, the second dose was more effective in males (OR = 0.090), as well as two doses (OR = 0.089) and three doses (OR = 0.090) among individuals aged 18-59. Whereas, when compared with the unvaccinated, one dose (OR = 7.715, 95% CI: 1.904 to 31.254) and three doses (OR = 2.055, 95% CI: 1.162 to 3.635) could contribute to the increased risk of Omicron infection after adjusting for sex and age. Meanwhile, by contrast with unvaccinated individuals, the result of increased risk was also manifested in the first dose in males (OR = 12.400) and one dose (OR = 21.500), two doses (OR = 1.890), and a booster dose (OR = 1.945) in people aged 18-59. In conclusion, the protective effect of full and booster vaccination with inactivated COVID-19 vaccines exceeded the incomplete vaccination, of which three doses were more effective. Nevertheless, vaccination may increase the risk of Omicron infection compared with unvaccinated people. This may result from the transmission traits of BA.2, the particularity and stronger protection awareness of the unvaccinated population, as well as the ADE effect induced by the decrease of antibody titers after a long time of vaccination. It is crucial to explore this issue in depth for the formulation of future COVID-19 vaccination strategies.

Effect of Vaccination Time Intervals on SARS-COV-2 Omicron Variant Strain Infection in Guangzhou: A Real-World Matched Case-Control Study.

In April 2022, a COVID-19 outbreak caused by the Omicron variant emerged in Guangzhou. A case-control study was conducted to explore the relationship between vaccination intervals and SARS-CoV-2 infection in the real world. According to the vaccination dose and age information of the cases, a 1:4 matched case-control sample was established, finally including n = 242 for the case group and n = 968 for the control group. The results indicated that among the participants who received three vaccine doses, those with an interval of more than 300 days between the receipt of the first vaccine dose and infection (or the first contact with a confirmed case) were less likely to be infected with SARS-CoV-2 than those with an interval of less than 300 days (OR = 0.67, 95% CI = 0.46-0.99). After age-stratified analysis, among participants aged 18-40 years who received two doses of vaccine, those who received the second dose more than 30 days after the first dose were less likely to be infected with SARS-CoV-2 (OR = 0.53, 95% CI = 0.30-0.96). Our findings suggest that we need to extend the interval between the first dose and the second dose and further explore the optimal interval between the first and second and between the second and third doses in order to improve vaccine efficacy.

Does potential antibody-dependent enhancement occur during SARS-CoV-2 infection after natural infection or vaccination? A meta-analysis.

Coronavirus disease 2019 (COVID-19) continues to constitute an international public health emergency. Vaccination is a prospective approach to control this pandemic. However, apprehension about the safety of vaccines is a major obstacle to vaccination. Amongst health professionals, one evident concern is the risk of antibody-dependent enhancement (ADE), which may increase the severity of COVID-19. To explore whether ADE occurs in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and increase confidence in the safety of vaccination, we conducted a meta-analysis to investigate the relationship between post-immune infection and disease severity from a population perspective. Databases, including PubMed, EMBASE, Chinese National Knowledge Infrastructure, SinoMed, Scopus, Science Direct, and Cochrane Library, were searched for articles on SARS-CoV-2 reinfection published until 25 October 2021. The papers were reviewed for methodological quality, and a random effects model was used to analyse the results. Heterogeneity was assessed using the I2 statistic. Publication bias was evaluated using a funnel plot and Egger's test. Eleven studies were included in the final meta-analysis. The pooled results indicated that initial infection and vaccination were protective factors against severe COVID-19 during post-immune infection (OR = 0.55, 95%CI = 0.31-0.98). A subgroup (post-immune infection after natural infection or vaccination) analysis showed similar results. Primary SARS-CoV-2 infection and vaccination provide adequate protection against severe clinical symptoms after post-immune infection. This finding demonstrates that SARS-CoV-2 may not trigger ADE at the population level.

Impact of Vaccination and Control Measures on the Fatality of COVID-19: An Ecological Study.

BACKGROUND: During the COVID-19 pandemic, reducing the case fatality rate (CFR) becomes an urgent goal. OBJECTIVE: This study explored the effect of vaccination and variants on COVID-19 fatality and provide a basis for the adjustment of control measures. METHODS: This study collected epidemiological information on COVID-19 from January to October 2021. By setting different lag times, we calculated the adjusted CFR. The Spearman correlation coefficient and beta regression were used to explore factors that may affect COVID-19 fatality. RESULTS: Every 1% increase in the percentage of full vaccinations may reduce the 3 weeks lagging CFR by 0.66%. Increasing the restrictions on internal movement from level 0 to 1, restrictions on international travel controls from level 2 to 3, and stay-at-home restrictions from level 0 to 2 were associated with an average reduction in 3 weeks lagging CFR of 0.20%, 0.39%, and 0.36%, respectively. Increasing strictness in canceling public events from level 0 to 1 and 2 may reduce the 3 weeks lagging CFR by 0.49% and 0.37, respectively. Increasing the severity of school and workplace closures from level 1 or level 0 to 3 may increase the 3 weeks lagging CFR of 0.39% and 0.83, respectively. Every 1-point increase in the Global Health Security (GHS) index score may increase the 3 weeks lagging CFR by 0.12%. CONCLUSION: A higher percentage of full vaccinations, higher levels of internal movement restrictions, international travel control restrictions, cancelations of public events, and stay-at-home restrictions are factors that may reduce the adjusted CFR.

Association between Mutations in Papain-like Protease (PLpro) of SARS-CoV-2 with COVID-19 Clinical Outcomes.

Papain-like protease (PLpro) is important for the replication and transcription of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to reveal the PLpro mutations associated with the clinical outcomes of patients. Due to the importance of the S protein in the pathogenicity of SARS-CoV-2, the mutation of the S protein was also analyzed in this study. After downloading the data from the Global Initiative on Sharing Avian Influenza Data (GISAID) database, samples were divided into two groups on the basis of patient status, namely, recovered and dead groups. This study performed a univariate analysis and further explored the association of mutations with patient outcomes through multivariate logistic regression analysis. A total of 138,492 samples were used for analysis. The patients had a mean age of 43.66 ± 21.56 years, and 51.3% of them were female. Multivariate logistic regression results showed that, compared with men, women had a lower risk of dying from coronavirus disease 2019 (COVID-19) (OR = 0.687, 95%CI: 0.638-0.740). Compared with patients aged 17 years and younger, patients aged 18-64 years (OR = 2.864, 95%CI: 1.982-4.139) and patients over 65 years old (OR = 19.135, 95%CI: 13.280-27.572) had a higher risk of death after infection. Compared with the wild type, P78L (OR = 5.185, 95%CI: 2.763-9.730) and K233Q (OR = 5.154, 95%CI: 1.442-18.416) in PLpro were associated with an increased risk of death. A synergistic interaction existed between age and mutations A146D and P78L. The results of the multivariate logistic regression analysis of the data on vaccinated patients demonstrated that, compared with the wild type, the P78L (OR = 3.376, 95%CI: 2.040-5.585) mutation was associated with an increased risk of death. In conclusion, compared with the wild-type PLpro protein, the P78L and K233Q mutations may increase the risk of death in infected individuals. In addition, a synergistic effect existed between age and P78L and K233Q that increased the risk of death in older patients.

Intelligent Extraction of Salient Feature From Electroencephalogram Using Redundant Discrete Wavelet Transform.

At present, electroencephalogram (EEG) signals play an irreplaceable role in the diagnosis and treatment of human diseases and medical research. EEG signals need to be processed in order to reduce the adverse effects of irrelevant physiological process interference and measurement noise. Wavelet transform (WT) can provide a time-frequency representation of a dynamic process, and it has been widely utilized in salient feature analysis of EEG. In this paper, we investigate the problem of translation variability (TV) in discrete wavelet transform (DWT), which causes degradation of time-frequency localization. It will be verified through numerical simulations that TV is caused by downsampling operations in decomposition process of DWT. The presence of TV may cause severe distortions of features in wavelet subspaces. However, this phenomenon has not attracted much attention in the scientific community. Redundant discrete wavelet transform (RDWT) is derived by eliminating the downsampling operation. RDWT enjoys the attractive merit of translation invariance. RDWT shares the same time-frequency pattern with that of DWT. The discrete delta impulse function is used to test the time-frequency response of DWT and RDWT in wavelet subspaces. The results show that DWT is very sensitive to the translation of delta impulse function, while RDWT keeps the decomposition results unchanged. This conclusion has also been verified again in decomposition of actual EEG signals. In conclusion, to avoid possible distortions of features caused by translation sensitivity in DWT, we recommend the use of RDWT with more stable performance in BCI research and clinical applications.

Two new clerodane diterpenoids and a new pyran-2-one derivative with anti-neuroinflammatory activities from Croton crassifolius.

Two new clerodane diterpenoids (1 and 2), a new pyran-2-one derivative (3), along with five known compounds (4‒8), were isolated from Croton crassifolius. Notably, crassifolin X (1) is a novel clerodane diterpenoid, characterized with a peculiar δ-lactone core being formed between C-1 and C-4. Their structures, including absolute configurations, were established on the basis of spectroscopic methods (UV, IR, HRESIMS and NMR), and circular dichroism experiments. In addition, all compounds were evaluated for their anti-neuroinflammatory activities based on the expression of TNF-α and IL-6 levels on LPS-induced BV2 cells, and compounds 1‒3 and 5 showed potential anti-neuroinflammatory activity.

Antiviral and Antioxidant Components from the Fruits of Illicium verum Hook.f. (Chinese Star Anise).

Illicium verum Hook.f. (Chinese star anise), a known Chinese traditional spice, is commonly applied in Chinese cuisine and cooking in Southeast Asia. As a kind of medicinal and edible resource, the fruit of I. verum has attracted great attention for its chemical constituents and physiological activities. In this work, the phytochemical study of the fruits of I. verum led to the isolation and identification of 20 compounds, including 6 new lignans and phenylpropanoids (1-6) and 14 known ones (7-20). Their structures were characterized by extensive analysis of spectroscopic data (IR, UV, high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), one-dimensional (1D) and two-dimensional (1D) NMR), electronic circular dichroism (ECD) calculation, and by comparison with literature data. Meanwhile, all compounds (1-20) were evaluated for their antiviral and antioxidant activities. Especially, compound 7 [(-)-bornyl p-coumarate] showed strong antiviral activities against influenza virus A/Puerto Rico/8/34 H1N1 (PR8) with an IC50 value of 1.74 ± 0.47 µM, which is much better than those of Tamiflu (IC50 = 10.01 ± 0.92 µM) and ribavirin (IC50 = 10.76 ± 1.60 µM). The antiviral activity against PR8 of compound 7 was reported for the first time, which was sufficiently confirmed by cell counting kit 8 (CCK-8), cytopathic effect (CPE) reduction, and immunofluorescence assays. In this study, the discovery of antiviral and antioxidant components from the fruits of I. verum could benefit the further development and utilization of this plant.

Suppressing of Power Line Artifact From Electroencephalogram Measurements Using Sparsity in Frequency Domain.

Electroencephalogram (EEG) plays an important role in brain disease diagnosis and research of brain-computer interface (BCI). However, the measurements of EEG are often exposed to strong interference of power line artifact (PLA). Digital notch filters (DNFs) can be applied to remove the PLA effectively, but it also results in severe signal distortions in the time domain. To address this problem, spectrum correction (SC) based methods can be utilized. These methods estimate harmonic parameters of the PLA such that compensation signals are produced to remove the noise. In order to ensure high accuracy during harmonic parameter estimations, a novel approach is proposed in this paper. This novel approach is based on the combination of sparse representation (SR) and SC. It can deeply mine the information of PLA in the frequency domain. Firstly, a ratio-based spectrum correction (RBSC) using rectangular window is employed to make rough estimation of the harmonic parameters of PLA. Secondly, the two spectral line closest to the estimated frequency are calculated. Thirdly, the two spectral lines with high amplitudes can be utilized as input of RBSC to make finer estimations of the harmonic parameters. Finally, a compensation signal, based on the extracted harmonic parameters, is generated to suppress PLA. Numerical simulations and actual EEG signals with PLA were used to evaluate the effectiveness of the improved approach. It is verified that this approach can effectively suppress the PLA without distorting the time-domain waveform of the EEG signal.

Water-soluble matrine-type alkaloids with potential anti-neuroinflammatory activities from the seeds of Sophora alopecuroides.

A phytochemical investigation on the alkaloids from water-soluble part of Sophora alopecuroides led to obtain forty matrine-type alkaloids (1-40) including eighteen new ones (1-18), which covers almost all positions of the oxygen substitution in matrine-type structure. Notably, eight compounds (1-8) belong to rare bis-amide matrine-type alkaloid. The new structures were determined based on extensive spectroscopic data, electronic circular dichroism (ECD) calculations, and six instances, verified by X-ray crystallography. Most of isolates showed anti-neuroinflammatory activities based on the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in BV2 microglia cells. Especially, compound 39 can suppress those two mediator secretions in a dose-dependent manner with IC50 values of 21.6 ± 0.5 and 16.7 ± 0.8 µM, respectively. Further mechanistic study revealed that 39 suppressed the phosphorylation of IκBα and p65 subunit to regulate the NF-κB signaling pathway.

Willingness to Receive SARS-CoV-2 Vaccination and Associated Factors among Chinese Adults: A Cross Sectional Survey.

Vaccination is a key strategy to prevent the pandemic caused by the coronavirus disease 2019 (COVID-19). This study aims to investigate the willingness of Chinese adults to be vaccinated against COVID-19 and further explore the factors that may affect their willingness. We used a self-design anonymous questionnaire to conduct an online survey via the Sojump. A total of 1009 valid questionnaires were analyzed. The age of the participants ranged from 18 to 74. Among them, 609 (60.4%, 95%CI: 57.4-63.4%) were willing to receive the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Logistic regression analysis results showed that the age of 30-49 (OR = 2.042, 95%CI: 1.098-3.799), universities and colleges education (OR = 1.873, 95% CI = 1.016-3.451), master degree or above education (OR = 1.885, 95%CI = 1.367-2.599), previous influenza vaccination history (OR = 2.176, 95%CI: 1.474-3.211), trust in the effectiveness of the vaccine (OR = 6.419, 95%CI: 3.717-11.086), and close attention to the latest news of the vaccine (OR = 1.601, 95%CI: 1.046-2.449) were facilitative factors that affected their willingness to be vaccinated. More than half of the adults in China would be willing to receive a SARS-CoV-2 vaccine. Middle-aged people with higher education, those who had been vaccinated against influenza, and those who believed that COVID-19 vaccine was effective and paid close attention to it were more willing to be vaccinated. Our findings can provide reference for the implementation of vaccination and the prevention of COVID-19 in China. More studies are needed after the vaccine is launched.

Mo0 and Mo4+ bimetallic reactive sites accelerating Fe2+/Fe3+ cycling for the activation of peroxymonosulfate with significantly improved remediation of aromatic pollutants.

In Fe2+/peroxymonosulfate (PMS) activation system, the slow cycle rate of Fe3+/Fe2+ has been considered to be the limiting step in the remediation of organic contaminants. In this paper, commercial molybdenum (Mo) powder is employed as the cocatalyst in Fe2+/PMS system, which can significantly accelerate the Fe3+/Fe2+ cycling efficiency by the exposed bimetallic active sites of Mo4+ and Mo0, and the process is accelerated as the amount of Mo powder increased. The Mo cocatalytic Fe2+/PMS system exhibits an enhanced performance for the activation of PMS and the removal of different aromatic pollutants including dyes, phenolic pollutants and antibiotics, in a wide pH range of 4.0-9.0. Importantly, Mo powder exhibits excellent cycle performance in the PMS activation system, and rhodamine B (RhB) can be removed within 10 min even after 5 cycles. Electron paramagnetic resonance (EPR) prove that the sulfate radicals (SO4-) is the major reactive oxides species in the PMS activation, the increase of Fe2+ content induced by the cocatalytic effect of Mo powder can effectively promote the production of SO4- and increase the utilization of PMS. In addition, to observe the process of pollutant removal more intuitively, HPLC-MS is used to analyze the decomposing pathway of RhB and sulfadiazine in Mo+FeSO4+PMS system. It is believed that this research provides a new idea for the efficient activation of PMS by iron ions in a wide initial pH range, which is expected to be applied to the treatment of large-scale industrial wastewater.