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Xiaohe K Xu,1 Brian P Harvey,2 Kenneth R Lutchen,2 Brian D Gelbman,3 Stephen L Monfre,1 Robert E Coifman,1 Charles E Forbes1 1Feather Sensors, LLC, Millville, NJ 08332, USA; 2Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA; 3Division of Pulmonary and Critical Care Medicine, Weill Cornell Medical Center, New York, NY 10065, USA Purpose: This study supports the use of thin-film micro-electro-mechanical system (MEMS) airflow sensors in the forced oscillation technique. Materials and methods: The study employed static testing using air flow standards and computer-controlled sound attenuations at 8 Hz. Human feasibility studies were conducted with a testing apparatus consisting of a pneumotach and thin-film MEMS air flow sensors in series. Short-time Fourier transform spectra were obtained using SIGVIEW software. Results: Three tests were performed, and excellent correlations were observed between the probes. The thin-film MEMS probe showed superior sensitivity to higher frequencies up to 200 Hz. Conclusion: The results suggest that lower-cost thin-film MEMS can be used for forced oscillation technique applications (including home care devices) that will benefit patients suffering from pulmonary diseases such as asthma, COPD, and cystic fibrosis. Keywords: pulmonary disease, pulmonary impedance, airway resistance, short-time Fourier transform, glottis closure

In fixed prosthodontics, clear exposure of the preparation margin is the prerequisite for obtaining accurate digital impressions and improving the marginal fit of restorations. To resolve the issues associated with the cord retraction technique, such as pain, acute injury, and prolonged procedural time, this study proposes a new technology for intraoral digital impression taking with pneumatic gingival retraction. The new scanning head blows a high-speed airflow that instantaneously separates the free gingiva, locally exposing the subgingival preparation margin. Combined with the farthest point preservation stitching algorithm based on the distance from the normal vector and high-speed laser scanning photography, it achieves global preparation edge data and gingival reconstruction, realizing painless, non-invasive, and efficient precise acquisition of the preparation margin. Using this new technique, a patient with a full porcelain crown restoration on a posterior tooth was treated. The digital impression revealed a clear margin of the preparation, and the crown made from this data has a good marginal fit.

Objective: To summarize the clinical, pathological and molecular characteristics of various types of pediatric glioma, and to explore the differences in the morphology and clinical significance among various types of pediatric glioma. Methods: Based on the fifth edition of the World Health Organization classification of central nervous system tumors, this study classified or reclassified 111 pediatric gliomas that were diagnosed at Guangzhou Medical University Affiliated Women and Children's Medical Center from January 2020 to June 2023. The clinical manifestations, imaging findings, histopathology, and molecular characteristics of these tumors were analyzed. Relevant literature was also reviewed. Results: The 111 patients with pediatric glioma included 56 males and 55 females, with the age ranging from 10 days to 13 years (average age, 5.5 years). Clinically, manifestations presented from 5 days to 8 years before the diagnosis, including epilepsy in 16 cases, increased intracranial pressure in 48 cases and neurological impairment in 66 cases. MRI examinations revealed tumor locations as supratentorial in 43 cases, infratentorial in 65 cases, and spinal cord in 3 cases. There were 73 cases presented with a solid mass and 38 cases with cystic-solid lesions. The largest tumor diameter ranged from 1.4 to 10.6 cm. Among the 111 pediatric gliomas, there were 6 cases of pediatric diffuse low-grade glioma (pDLGG), 63 cases of circumscribed astrocytoma glioma (CAG), and 42 cases of pediatric diffuse high-grade glioma (pDHGG). Patients with pDLGG and CAG were younger than those with pDHGG. The incidence of pDLGG and CAG was significantly lower in the midline of the infratentorial region compared to that of pDHGG. They were more likely to be completely resected surgically. The pDLGG and CAG group included 4 cases of pleomorphic xanthoastrocytoma, showing histological features of high-grade gliomas. Among the high-grade gliomas, 13 cases were diffuse midline gliomas and also showed histological features of low-grade glioma. Immunohistochemical studies of H3K27M, H3K27ME3, p53, ATRX, BRAF V600E, and Ki-67 showed significant differences between the pDLGG and CAG group versus the pDHGG group ( P <0.01). Molecular testing revealed that common molecular variations in the pDLGG and CAG group were KIAA1549-BRAF fusion and BRAF V600E mutation, while the pDHGG group frequently exhibited mutations in HIST1H3B and H3F3A genes, 1q amplification, and TP53 gene mutations. With integrated molecular testing, 2 pathological diagnoses were revised, and the pathological subtypes of 35.3% (12/34) of the pediatric gliomas that could not be reliably classified by histology were successfully classified. Conclusions: There are significant differences in clinical manifestations, pathological characteristics, molecular variations, and prognosis between the pDLGG, CAG and pDHGG groups. The integrated diagnosis combining histology and molecular features is of great importance for the accurate diagnosis and treatment of pediatric gliomas.

The serial interval distribution is used to approximate the generation time distribution, an essential parameter to infer the transmissibility (${R}&#95;t$) of an epidemic. However, serial interval distributions may change as an epidemic progresses. We examined detailed contact tracing data on laboratory-confirmed cases of COVID-19 in Hong Kong during the five waves from January 2020 to July 2022. We reconstructed the transmission pairs and estimated time-varying effective serial interval distributions and factors associated with longer or shorter intervals. Finally, we assessed the biases in estimating transmissibility using constant serial interval distributions. We found clear temporal changes in mean serial interval estimates within each epidemic wave studied and across waves, with mean serial intervals ranged from 5.5 days (95% CrI: 4.4, 6.6) to 2.7 (95% CrI: 2.2, 3.2) days. The mean serial intervals shortened or lengthened over time, which were found to be closely associated with the temporal variation in COVID-19 case profiles and public health and social measures and could lead to the biases in predicting ${R}&#95;t$. Accounting for the impact of these factors, the time-varying quantification of serial interval distributions could lead to improved estimation of ${R}&#95;t$, and provide additional insights into the impact of public health measures on transmission., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Networks offer a powerful approach to modeling complex systems by representing the underlying set of pairwise interactions. Link prediction is the task that predicts links of a network that are not directly visible, with profound applications in biological, social, and other complex systems. Despite intensive utilization of the topological feature in this task, it is unclear to what extent a feature can be leveraged to infer missing links. Here, we aim to unveil the capability of a topological feature in link prediction by identifying its prediction performance upper bound. We introduce a theoretical framework that is compatible with different indexes to gauge the feature, different prediction approaches to utilize the feature, and different metrics to quantify the prediction performance. The maximum capability of a topological feature follows a simple yet theoretically validated expression, which only depends on the extent to which the feature is held in missing and nonexistent links. Because a family of indexes based on the same feature shares the same upper bound, the potential of all others can be estimated from one single index. Furthermore, a feature's capability is lifted in the supervised prediction, which can be mathematically quantified, allowing us to estimate the benefit of applying machine learning algorithms. The universality of the pattern uncovered is empirically verified by 550 structurally diverse networks. The findings have applications in feature and method selection, and shed light on network characteristics that make a topological feature effective in link prediction., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Our continued works on the chemical constituents of Ginkgo biloba (G. biloba) leaves has led to the isolation of two novel phenylbutenoids (1, 2), along with five previously unidentified terpene glycosides (3-7). Among them, compounds 1 and 2 represent unique (Z)-phenylbutenoids, 3-6 are megastigmane glycosides, and 7 is identified as a rare bilobanone glycoside (Fig. 1). This study marks the first reported isolation of phenylbutenoid and bilobanone glycoside from G. biloba. The chemical structures of these compounds were elucidated through extensive spectroscopic analysis, including HR-ESI-MS and various 1D and 2D NMR experiments. Furthermore, the absolute configurations of these molecules were determined using Mosher's method, ECD experiments, and Cu-Kα X-ray crystallographic analyses., (Copyright © 2024 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Understanding different gender roles forms part of the efforts to reduce gender inequality. This paper analyses COVID-19 family clusters outside Hubei Province in mainland China during the 2020 outbreak, revealing significant differences in spreading patterns across gender and family roles. Results show that men are more likely to be the imported cases of a family cluster, and women are more likely to be infected within the family. This finding provides new supportive evidence of the 'men as breadwinner and women as homemaker' (MBWH) gender roles in China. Further analyses reveal that the MBWH pattern is stronger in eastern than in western China, stronger for younger than for elder people. This paper offers not only valuable references for formulating gender-differentiated epidemic prevention policies but also an exemplification for studying group differences in similar scenarios.

The lack of systems to automatically extract epidemiological fields from open-access COVID-19 cases restricts the timeliness of formulating prevention measures. Here we present a protocol for using CCIE, a COVID-19 Cases Information Extraction system based on the pre-trained language model. 1 We describe steps for preparing supervised training data and executing python scripts for named entity recognition and text category classification. We then detail the use of machine evaluation and manual validation to illustrate the effectiveness of CCIE. For complete details on the use and execution of this protocol, please refer to Wang et al. 2 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To observe the effect of acupuncture of "Tianshu"(ST25) at different depths on colonic transportation function, expressions of colonic substance P (SP) and interstitial cells of Cajal (ICC) in rats with slow transit constipation (STC), so as to explore its mechanisms underlying improvement of STC．., Methods: Fifty male Wistar rats were selected and randomly divided into control，STC model，conventional acupuncture，deep needling group 1 and deep needling group 2 groups，with 10 rats in each group．The STC model was established by gavage of 1 mg/mL compound diphenoxylate suspension (10 mg/kg), once every other day for 21 days, and rats of the control group were given the same dose of distilled water by gavage．EA (2 Hz, 2 mA) was applied to "Tianshu"(ST25), with the acupuncture needle inserted to a depth of 3 mm for rats of the conventional acupuncture group, 4.5 mm for those of deep needling group 1, and 10 mm for those of the deep needling group 2. The acupuncture needle was twirled for 1 min, then retained for 15 min each time, once a day for 15 consecutive days．Following modeling, rats of the 4 groups and the control group received gavage of active carbon 2 mL (100 g/L) for observing the excretion time of the first black stool grain to assess the intestinal transit function. The colonic myoelectric activities (frequency and amplitude) were recorded by using BIOPAC multichannel physiograph. The immunoactivity of SP and c-kit (a transmembrane protein kinase for identification of ICC) of colonic musculature was detected by immunohistochemistry., Results: Compared with the control group，the time of excretion of the first black stool grain, and the amplitude of colonic electromyogram (EMG) were significantly increased ( P <0.01), while the frequency of EMG, expressions of SP and c-kit (ICC) were significantly decreased in the model group ( P <0.01). In contrast to the model group, both deep needling group 1 and 2 had a decrease in the time of excretion of the first black stool grain, and amplitude of intestinal EMG, and an increase of frequency of intestinal EMG, and immunoactivity of SP and c-kit ( P <0.01). The effect of deep needling 2 is superior to that of deep needling 1 in reducing the time of excretion of the first black stool grain ( P <0.05), lowering the amplitude of EMG of the gut smooth muscle ( P <0.05) and in increasing the frequency of EMG ( P <0.05) and the expressions of SP and c-kit ( P <0.05). No significant changes were found in the levels of frequency and amplitude of EMG, and expressions of SP and c-kit after routine needling in comparison with the model group ( P >0.05), except the excretion time of the first black stool grain ( P <0.05)., Conclusion: Deep needling at ST25 at depth of 4.5 mm and 10 mm，especially at depth of 10 mm，has a significant effect in promoting gut motility to ameliorate constipation in rats with STC, which may be related to its function in up-regulating the expressions of SP and ICC activity.

The large population movement during the Spring Festival travel in China can considerably accelerate the spread of epidemics, especially after the relaxation of strict control measures against COVID-19. This study aims to assess the impact of population migration in Spring Festival holiday on epidemic spread under different scenarios. Using inter-city population movement data, we construct the population flow network during the non-holiday time as well as the Spring Festival holiday. We build a large-scale metapopulation model to simulate the epidemic spread among 371 Chinese cities. We analyze the impact of Spring Festival travel on the peak timing and peak magnitude nationally and in each city. Assuming an R 0 (basic reproduction number) of 15 and the initial conditions as the reported COVID-19 infections on 17 December 2022, model simulations indicate that the Spring Festival travel can substantially increase the national peak magnitude of infection. The infection peaks arrive at most cities 1-4 days earlier as compared to those of the non-holiday time. While peak infections in certain large cities, such as Beijing and Shanghai, are decreased due to the massive migration of people to smaller cities during the pre-Spring Festival period, peak infections increase significantly in small- or medium-sized cities. For a less transmissible disease ( R 0 = 5), infection peaks in large cities are delayed until after the Spring Festival. Small- or medium-sized cities may experience a larger infection due to the large-scale population migration from metropolitan areas. The increased disease burden may impose considerable strain on the healthcare systems in these resource-limited areas. For a less transmissible disease, particular attention needs to be paid to outbreaks in large cities when people resume work after holidays.

Euodiae Fructus, referred to as "Wuzhuyu" in Chinese, has been used as local and traditional herbal medicines in many regions, especially in China, Japan and Korea, for the treatment of gastrointestinal disorders, headache, emesis, aphtha, dermatophytosis, dysentery, etc. Substantial investigations into their chemical and pharmacological properties have been performed. Recently, interest in this plant has been focused on the different structural types of alkaloids like evodiamine, rutaecarpine, dehydroevodiamine and 1-methyl-2-undecyl-4(1H)-quinolone, which exhibit a wide range of pharmacological activities in preclinical models, such as anticancer, antibacterial, anti-inflammatory, anti-cardiovascular disease, etc. This review summarizes the up-to-date and comprehensive information concerning the botany, traditional uses, phytochemistry, pharmacology of Euodiae Fructus together with the toxicology and quality control, and discusses the possible direction and scope for future research on this plant., (© 2023. The Author(s).)

Human mobility restriction policies have been widely used to contain the coronavirus disease-19 (COVID-19). However, a critical question is how these policies affect individuals' behavioral and psychological well-being during and after confinement periods. Here, we analyze China's five most stringent city-level lockdowns in 2021, treating them as natural experiments that allow for examining behavioral changes in millions of people through smartphone application use. We made three fundamental observations. First, the use of physical and economic activity-related apps experienced a steep decline, yet apps that provide daily necessities maintained normal usage. Second, apps that fulfilled lower-level human needs, such as working, socializing, information seeking, and entertainment, saw an immediate and substantial increase in screen time. Those that satisfied higher-level needs, such as education, only attracted delayed attention. Third, human behaviors demonstrated resilience as most routines resumed after the lockdowns were lifted. Nonetheless, long-term lifestyle changes were observed, as significant numbers of people chose to continue working and learning online, becoming "digital residents." This study also demonstrates the capability of smartphone screen time analytics in the study of human behaviors., Supplementary Information: The online version contains supplementary material available at 10.1140/epjds/s13688-023-00391-9., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2023.)

Radiation-induced intestinal damage (RIID) is a serious disease with limited effective treatment. Nuclear explosion, nuclear release, nuclear application and especially radiation therapy are all highly likely to cause radioactive intestinal damage. The intestinal microecology is an organic whole with a symbiotic relationship formed by the interaction between a relatively stable microbial community living in the intestinal tract and the host. Imbalance and disorders of intestinal microecology are related to the occurrence and development of multiple systemic diseases, especially intestinal diseases. Increasing evidence indicates that the gut microbiota and its metabolites play an important role in the pathogenesis and prevention of RIID. Radiation leads to gut microbiota imbalance, including a decrease in the number of beneficial bacteria and an increase in the number of harmful bacteria that cause RIID. In this review, we describe the pathological mechanisms of RIID, the changes in intestinal microbiota, the metabolites induced by radiation, and their mechanism in RIID. Finally, the mechanisms of various methods for regulating the microbiota in the treatment of RIID are summarized., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Xianpeng Zu reports financial support was provided by National Natural Science Foundation of China. Xianpeng Zu reports financial support was provided by National Key Research and Development Program of China. Xianpeng Zu reports financial support was provided by Shanghai Municipal Health Commission Project. Xianpeng Zu reports financial support was provided by Three-year Action Plan for Shanghai TCM Development and Inheritance Program. Xianpeng Zu reports was provided by Sailing Program of Naval Medical University., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The generation time distribution, reflecting the time between successive infections in transmission chains, is a key epidemiological parameter for describing COVID-19 transmission dynamics. However, because exact infection times are rarely known, it is often approximated by the serial interval distribution. This approximation holds under the assumption that infectors and infectees share the same incubation period distribution, which may not always be true. We estimated incubation period and serial interval distributions using 629 transmission pairs reconstructed by investigating 2989 confirmed cases in China in January-February 2020, and developed an inferential framework to estimate the generation time distribution that accounts for variation over time due to changes in epidemiology, sampling biases and public health and social measures. We identified substantial reductions over time in the serial interval and generation time distributions. Our proposed method provides more reliable estimation of the temporal variation in the generation time distribution, improving assessment of transmission dynamics., (© 2022. The Author(s).)

Background: The transmission dynamics of influenza were affected by public health and social measures (PHSMs) implemented globally since early 2020 to mitigate the COVID-19 pandemic. We aimed to assess the effect of COVID-19 PHSMs on the transmissibility of influenza viruses and to predict upcoming influenza epidemics., Methods: For this modelling study, we used surveillance data on influenza virus activity for 11 different locations and countries in 2017-22. We implemented a data-driven mechanistic predictive modelling framework to predict future influenza seasons on the basis of pre-COVID-19 dynamics and the effect of PHSMs during the COVID-19 pandemic. We simulated the potential excess burden of upcoming influenza epidemics in terms of fold rise in peak magnitude and epidemic size compared with pre-COVID-19 levels. We also examined how a proactive influenza vaccination programme could mitigate this effect., Findings: We estimated that COVID-19 PHSMs reduced influenza transmissibility by a maximum of 17·3% (95% CI 13·3-21·4) to 40·6% (35·2-45·9) and attack rate by 5·1% (1·5-7·2) to 24·8% (20·8-27·5) in the 2019-20 influenza season. We estimated a 10-60% increase in the population susceptibility for influenza, which might lead to a maximum of 1-5-fold rise in peak magnitude and 1-4-fold rise in epidemic size for the upcoming 2022-23 influenza season across locations, with a significantly higher fold rise in Singapore and Taiwan. The infection burden could be mitigated by additional proactive one-off influenza vaccination programmes., Interpretation: Our results suggest the potential for substantial increases in infection burden in upcoming influenza seasons across the globe. Strengthening influenza vaccination programmes is the best preventive measure to reduce the effect of influenza virus infections in the community., Funding: Health and Medical Research Fund, Hong Kong., Competing Interests: Declaration of interests BJC reports honoraria from AstraZeneca, Fosun Pharma, GSK, Moderna, Pfizer, Roche, and Sanofi. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Although open-access data are increasingly common and useful to epidemiological research, the curation of such datasets is resource-intensive and time-consuming. Despite the existence of a major source of COVID-19 data, the regularly disclosed case reports were often written in natural language with an unstructured format. Here, we propose a computational framework that can automatically extract epidemiological information from open-access COVID-19 case reports. We develop this framework by coupling a language model developed using deep neural networks with training samples compiled using an optimized data annotation strategy. When applied to the COVID-19 case reports collected from mainland China, our framework outperforms all other state-of-the-art deep learning models. The information extracted from our approach is highly consistent with that obtained from the gold-standard manual coding, with a matching rate of 80%. To disseminate our algorithm, we provide an open-access online platform that is able to estimate key epidemiological statistics in real time, with much less effort for data curation., Competing Interests: All authors declare no competing interests., (© 2022 The Authors.)

Ethnopharmacological Relevance: Dingkun Pill (DKP), a traditional Chinese medicine prescription, was modified from Bujing decoction and Xusijiangsheng pill by the imperial physician in the Qing dynasty (1700' s). It was believed to treat various gynecological diseases by nourishing qi and blood. Accumulating evidence indicates that it is effective in treating polycystic ovary syndrome (PCOS). However, the therapeutic efficacy and mechanism of action DKP against PCOS need to be further elucidated., Aim of the Study: To investigate the therapeutic effect and action mechanism of DKP against PCOS using an integrated approach of metabolomics and network pharmacology., Materials and Methods: The rat model of PCOS was established by dehydroepiandrosterone. An integrated metabolomics and network pharmacology strategy was applied to systemically clarify the mechanism of DKP against PCOS. Theca cells were prepared to evaluate the effect of DKP and its ingredients on testosterone synthesis in vitro., Results: The pharmacological experiments demonstrated that DKP could effectively convert the disordered estrous cyclicity, decrease the level of testosterone and the luteinizing hormone/follicle stimulating hormone ratio, and inhibit abnormal follicle formation in PCOS rats. By metabolomics analysis, 164 serum endogenous differential metabolites and 172 urine endogenous differential metabolites were tentatively identified. Steroid hormone biosynthesis and ovarian steroidogenesis were the most significantly impacted pathways. Based on network pharmacology and metabolomics studies, the ingredient-target-pathway network of DKP in the treatment of PCOS was constructed. Among the 10 key targets, CYP17A1, CYP19A1, STS, AR, ESR1, and MYC were closely involved in ovarian androgen synthesis. In theca cell-based assay of testosterone synthesis, DKP and its two active compounds (ligustilide and picrocrocin) showed inhibitory effects., Conclusion: DKP effectively improved symptoms in rats with dehydroepiandrosterone-induced PCOS. The mechanism of DKP in the treatment of PCOS is related to the CYP17A1 enzyme required for androgen synthesis., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Hypothalamus-pituitary-adrenal (HPA) axis plays critical roles in stress responses under challenging conditions such as hypoxia, via regulating gene expression and integrating activities of hypothalamus-pituitary-targets cells. However, the transcriptional regulatory mechanisms and signaling pathways of hypoxic stress in the pituitary remain to be defined. Here, we report that hypoxia induced dynamic changes in the transcription factors, hormones, and their receptors in the adult rat pituitary. Hypoxia-inducible factors (HIFs), oxidative phosphorylation, and cAMP signaling pathways were all differentially enriched in genes induced by hypoxic stress. In the pituitary gene network, hypoxia activated c-Fos and HIFs with specific pituitary transcription factors ( Prop1) , targeting the promoters of hormones and their receptors. HIF and its related signaling pathways can be a promising biomarker during acute or constant hypoxia. Hypoxia stimulated the transcription of marker genes for microglia, chemokines, and cytokine receptors of the inflammatory response. Corticotropin-releasing hormone receptor 1 (CRHR1) mediated the transcription of Pomc , Sstr2 , and Hif2a , and regulated the function of HPA axis. Together with HIF, c-Fos initiated and modulated dynamic changes in the transcription of hormones and their receptors. The receptors were also implicated in the regulation of functions of target cells in the pituitary network under hypoxic stress. CRHR1 played an integrative role in the hypothalamus-pituitary-target axes. This study provides new evidence for CRHR1 involved changes of hormones, receptors, signaling molecules and pathways in the pituitary induced by hypoxia., 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 Wang, Xia, Gong, Xu, Lv, Chatoo, Shamsi, Zhang, Liu, Liu, Zhang, Lu, Zhao, Du and Chen.)

As our ongoing interest to search bioactive dimeric sesquiterpenes from the genus Vladimiria (Asteraceae), the plant of Vladimiria souliei was studied. Based on the repetitive chromatographic fractionation, a chemical investigation on the roots of Vladimiria souliei led to the isolation and the identification of four previously undescribed sesquiterpene dimers, vlasouliodes A-D (1-4). Their chemical structures were elucidated by comprehensive analysis of spectroscopic data, including HRESIMS, 1D and 2D NMR spectroscopic data. The absolute configurations of them were unambiguously established by the experimental and calculated ECD data. In the in vitro biological activity evaluation, 1 and 3 displayed pronounced inhibitory activity against human breast adenocarcinoma cell lines (MCF-7) with IC 50 values of 17.12 ± 0.42 μM and 13.12 ± 0.10 μM, respectively. Additionally, treatment with 1 and 3 induced cell apoptosis in MCF-7 cells, down-regulated the expression of Caspase-3 and up-regulated the expression of Cleaved-caspase-3., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To observe the effect of electroacupuncture (EA) of bilateral "Tianshu"(ST25) at different frequencies on the first black stool discharge time, colonic electromyography (EMG) and immunoactivity of vasoactive intestinal peptide (VIP) and substance P (SP) in the colon tissue in rats with slow transit constipation (STC), so as to choose a better stimulating frequency in the treatment of STC., Methods: A total of 50 male Wistar rats were randomized into control, model, 2 Hz-EA, 100 Hz- EA, and 2 Hz/100 Hz-EA groups, with 10 rats in each group. The STC model was established by intraperitoneal injection of compound diphenoxylate suspension fluid (10 mg/kg). EA was applied to bilateral ST25 for 30 min, once a day for 14 consecutive days. The discharge time for the first black stool was recorded after gavage of mixed suspension fluid of active carbon (2 mL) for assessing the gastrointestinal motility. The colonic EMG was recorded by using a pair of silver electrodes and bioelectric amplifier. The expression of SP and VIP in the colonic tissue was detected by immunohistochemistry., Results: Following mode-ling, the colonic EMG amplitude, the discharge time for the first black stool and VIP immunoactivity were significantly increased ( P <0.01), and the EMG frequency and SP immunoactivity were significantly decreased （ P <0.01） in the model group compared with the control group. Compared with the model group, the increase of the discharge time for the first black stool, EMG amplitude and VIP immunoactivity, the decrease of EMG frequency and SP immunoactivity were reversed in the 3 EA groups ( P <0.01, P <0.05). The therapeutic effect of 100 Hz-EA was notably weaker than that of both 2 Hz-EA and 2 Hz/100 Hz-EA in up-regulating EMG frequency and SP immunoactivity and in down-regulating the discharge time for the first black stool, EMG amplitude and VIP immunoactivity ( P <0.05, P <0.01). There was no significant difference between the 2 Hz/100 Hz-EA and 2 Hz-EA groups ( P >0.05)., Conclusion: EA can accelerate colonic EMG activities, which may be associated with its functions in down-regulating VIP immunoactivity and up-regulating SP immunoactivity in the colonic tissues. The therapeutic effects of 2 Hz/100 Hz-EA and 2 Hz-EA are better than that of 100 Hz-EA.

Sophorae tonkinensis Radix et Rhizoma (S. tonkinensis) has been recorded as a 'poisonous' Chinese herbal medicine in Chinese Pharmacopoeia 2020. The clinical reaction reports of S. tonkinensis indicated its neurotoxicity; however, there still exists dispute about its toxic substances. At present, no report is available on the blood and brain prototype research of S. tonkinensis. Most studies focused on alkaloids and less on other compounds. Moreover, the constituents absorbed into the blood and brain have been rarely investigated so far. This study established a rapid and efficient qualitative analysis method using UPLC-Q-TOF-MS E to characterize the ingredients of S. tonkinensis and those entering into the rat's body after oral administration. A total of 91 compounds were identified in S. tonkinensis, of which 28 were confirmed by the standards. In addition, 30 and 19 prototypes were also first identified in the rat's blood and brain, respectively. It was found that most flavonoids, except alkaloids, were detected in the rat's body and distributed in the cerebrospinal fluid, suggesting that flavonoids may be one of the important toxic or effective substances of S. tonkinensis. This finding provides new clues and data for clarifying the toxicity or efficacy of this medicinal plant., (© 2022 John Wiley & Sons, Ltd.)

Background: Estimates of the serial interval distribution contribute to our understanding of the transmission dynamics of coronavirus disease 2019 (COVID-19). Here, we aimed to summarize the existing evidence on serial interval distributions and delays in case isolation for COVID-19., Methods: We conducted a systematic review of the published literature and preprints in PubMed on 2 epidemiological parameters, namely, serial intervals and delay intervals relating to isolation of cases for COVID-19 from 1 January 2020 to 22 October 2020 following predefined eligibility criteria. We assessed the variation in these parameter estimates using correlation and regression analysis., Results: Of 103 unique studies on serial intervals of COVID-19, 56 were included, providing 129 estimates. Of 451 unique studies on isolation delays, 18 were included, providing 74 estimates. Serial interval estimates from 56 included studies varied from 1.0 to 9.9 days, while case isolation delays from 18 included studies varied from 1.0 to 12.5 days, which were associated with spatial, methodological, and temporal factors. In mainland China, the pooled mean serial interval was 6.2 days (range, 5.1-7.8) before the epidemic peak and reduced to 4.9 days (range, 1.9-6.5) after the epidemic peak. Similarly, the pooled mean isolation delay related intervals were 6.0 days (range, 2.9-12.5) and 2.4 days (range, 2.0-2.7) before and after the epidemic peak, respectively. There was a positive association between serial interval and case isolation delay., Conclusions: Temporal factors, such as different control measures and case isolation in particular, led to shorter serial interval estimates over time. Correcting transmissibility estimates for these time-varying distributions could aid mitigation efforts., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Three new monoterpene alkaloids, delavatines C-E (1-3), along with five known ones (4-8), were separated from the whole plants of Incarvillea delavayi. All compounds were deduced by interpretation of comprehensive NMR spectral data and X-Ray single crystal diffraction, in combination with a quantum chemical calculation of NMR chemical shift coupled with an advanced statistical procedure DP4+. Compounds 1-8 were assessed NO suppressive effect in LPS-stimulated BV2 microglia cells. Compounds 2, 3, 6, and 8 exhibited significant inhibition against NO production in LPS-induced BV2 cells with IC 50 values of 25.62, 17.29, 19.94 and 23.88 μM, stronger than or comparable to the positive control (AG) with IC 50 value of 26.13 μM., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)

Dingkun Dan (DKD), a reputable traditional Chinese medicine formula, has been used to treat gynecological diseases and showed significant clinical effects since ancient times. However, the application and development of DKD are seriously hampered by the unclear active substances. Structural characterization of compounds absorbed in vivo and their corresponding metabolites is significant for clarifying the pharmacodynamic material basis. In this study, an integrated strategy using ultra-performance liquid chromatography, coupled with quadrupole time-of-flight mass spectrometry and UNIFI™ software, was used to identify prototypes and metabolites after oral administration of DKD in rats. As a result, a total of 261 compounds, including 140 prototypes and 121 metabolites, were tentatively characterized in rat plasma, urine, and feces. The metabolic pathways of prototypes have been studied to clarify their possible transformation process in vivo. Moreover, an in vitro metabolism study was applied for verifying the metabolites under simulating the metabolic environment in vivo. This first systematic metabolic study of DKD is important for elucidating the metabolites and metabolic pathways and could provide a scientific basis for explaining the integrative mechanism in further pharmacology study., (© 2021 John Wiley & Sons, Ltd.)

Objective: To evaluate the safety of thread embedding acupuncture therapy (TEAT) and discuss the prevention and treatment of some adverse events (AEs)., Methods: Review of databases, including China National Knowledge Infrastructure (CNKI), CBMdisc, Wanfang, VIP databases and English literature published in PubMed, MEDLINE, EMBASE and Web of Science, were searched from their inception to January 2020, randomized controlled trials (RCTs) and case reports in which AEs with TEAT were included. Cochrane Collaboration's tool and RevMan V.5.3.3 software were used to evaluate the quality of the studies., Results: A total of 61 studies (45 RCTs and 16 case reports) with 620 cases of AEs were included in this review. These studies were published in two countries: China and South Korea. Twenty eight kinds of AEs were summarized. The most common AEs were induration, bleeding and ecchymosis, redness and swelling, fever, and pain. They were accounted for 75.35% (425/564) in the review, and most of them were mild. The rarest AEs were epilepsy, irregular menstruation, skin ulcer, thread malabsorption, and fat liquefaction, with 1 case each. But not all of them had clear causal relationship with TEAT. Most of the AEs were local reactions [with incidence of 9.83% (480/4,882)] and systemic reactions accounted for only 1.27% (62/4,882). Although the included studies showed that AEs were very commonly encountered (11.09%), only 5 cases of severe AEs reported from 2013 to 2017 (0.1%) by using catgut thread, which are rarely seen nowdays with the wide use of new absorbable surgical suture. All of the severe AEs were recovered after symptomatic treatment with no sequelae., Conclusions: The evidence showed that TEAT is a relatively safe and convenient therapy especially since application of new absorbable surgical suture. Improving practitioner skills, regulating operations, and paying attention to the patients' conditions may reduce the incidence of AEs and improve safety of TEAT., (© 2021. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Ingenol, as the precursor of the marketed drug ingenol mebutate, has been proven to have a variety of bioactivities. The purpose of this study was to identify the metabolites of ingenol using ultra-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-Q/TOF-MS) combined with UNIFI software. Plasma, urine and fecal samples of rats were obtained and analyzed. A total of 18 metabolites were detected and identified in rat, including five phase II metabolites (M14-M18). Moreover, as microbial biotransformation is helpful to obtain sufficient reference standards of metabolites, the co-culture of ingenol with the fungus Cunninghamella elegans bio-110930 was also studied and yielded 4 phase I metabolites, in which reference standards of three metabolites were further obtained by preparative scale biotransformation. By matching their retention times, accurate masses, and fragment ions with metabolites in rat, the structures of three metabolites (M2, M3 and M4) were unambiguously confirmed by NMR technology. The results revealed that C. elegans bio-110930 functioned as an appropriate model to mimic and prepare phase I metabolism of ingenol in vivo to a certain extent. It also revealed that hydroxylation, oxygenation, sulfonation, and glucuronidation were the major metabolic pathways of ingenol. Furthermore, the first systematic metabolic study of ingenol is of great significance to elucidate the metabolites and metabolic pathways in vivo , which is helpful to predict metabolites of ingenol in humans, understand the elimination mechanism of ingenol, and clarify its effectiveness and toxicity., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objective: To establish a speech recognition system based on adaptive technology and to evaluate its value in pathological grossing processes. Methods: A total of 600 tissue specimens were collected at the Zhejiang Provincial People's Hospital affiliated to Hangzhou Medical College between October 1, 2020 and December 31, 2020. A speech recognition system based on adaptive technology was used in the pathological grossing processes, and the pathological examination reports were generated and extracted. Results: The speech recognition system based on adaptive technology showed a good recognition rate (overall recognition rate = 77.87%) and helped achieve rapid input and output of pathological examination data. Conclusions: The speech recognition system can reduce the labor costs, improve the work efficiency of pathologists and increase the quality of medical services, which may be valuable for building next-generation smart hospitals.

Predicting information cascade plays a crucial role in various applications such as advertising campaigns, emergency management and infodemic controlling. However, predicting the scale of an information cascade in the long-term could be difficult. In this study, we take Weibo, a Twitter-like online social platform, as an example, exhaustively extract predictive features from the data, and use a conventional machine learning algorithm to predict the information cascade scales. Specifically, we compare the predictive power (and the loss of it) of different categories of features in short-term and long-term prediction tasks. Among the features that describe the user following network, retweeting network, tweet content and early diffusion dynamics, we find that early diffusion dynamics are the most predictive ones in short-term prediction tasks but lose most of their predictive power in long-term tasks. In-depth analyses reveal two possible causes of such failure: the bursty nature of information diffusion and feature temporal drift over time. Our findings further enhance the comprehension of the information diffusion process and may assist in the control of such a process., (© 2021 The Authors.)

Type 2 diabetes mellitus( T2 DM) is a common chronic metabolic disease characterized by persistent hyperglycemia and insulin resistance. In pancreatic β-cells,glucose-stimulated insulin secretion( GSIS) plays a pivotal role in maintaining the balance of blood glucose level. Previous studies have shown that geniposide,one of the active components of Gardenia jasminoides,could quickly regulate the absorption and metabolism of glucose,and affect glucose-stimulated insulin secretion in pancreatic β cells,but the specific mechanism needs to be further explored. Emerging evidence indicated that glycosylation of glucose transporter( GLUT) has played a key role in sensing cell microenvironmental changes and regulating glucose homeostasis in eucaryotic cells. In this study,we studied the effects of geniposide on the key molecules of GLUT2 glycosylation in pancreatic β cells. The results showed that geniposide could significantly up-regulate the mRNA and protein levels of Glc NAc T-Ⅳa glycosyltransferase( Gn T-Ⅳa) and galectin-9 but had no signi-ficant effect on the expression of clathrin,and geniposide could distinctively regulate the protein level of Gn T-Ⅳa in a short time( 1 h) under the conditions of low and medium glucose concentrations,but had no significant effect on the protein level of galectin-9. In addition,geniposide could also remarkably affect the protein level of glycosylated GLUT2 in a short-time treatment. The above results suggested that geniposide could quickly regulate the protein level of Gn T-Ⅳa,a key molecule of protein glycosylation in INS-1 rat pancreatic βcells and affect the glycosylation of GLUT2. These findings suggested that the regulation of geniposide on glucose absorption,metabolism and glucose-stimulated insulin secretion might be associated with its efficacy in regulating GLUT2 glycosylation and affecting its distribution on the cell membrane and cytoplasm in pancreatic β cells.

Rationale: Todd paralysis (a stroke-like presentation in some patients with epilepsy) caused by limbic encephalitis (LE) is not easily distinguished from acute ischemic stroke by clinicians in the emergency room., Patient Concerns: We report a contactin-associated protein-like 2-antibody (CASPR2-Ab)-positive patient who presented with atypical LE., Diagnoses: CASPR2-Ab-positive LE was the presumed diagnosis. Re-evaluation of cerebrospinal fluid (CSF) samples revealed autoantibodies targeting CASPR2 at an immunoglobulin G titer of 1:1. The clinical presentation of subacute onset seizures, abnormal electroencephalography, hypermetabolism on positron emission tomography, good immunotherapy response, and the presence of specific antibodies in serum supports a diagnosis of autoimmune LE., Intervention: The patient received glucocorticoids (1 g for 3 days and 500 mg for 3 days), immunoglobulin (25 g for 3 days), sodium valproate (1 g for 3 days), and clonazepam (1 mg for 3 days)., Outcomes: Remission of temporal lobe epilepsy symptoms and cognitive dysfunction was observed. Follow-up analysis of CSF and serological examination were not approved by the patient. His Mini-Mental State Examination score improved to 21/30. Stable remission of symptoms was achieved throughout the follow-up period of 50 days., Lessons: Autoimmune encephalitis (AE) should be considered in cases of late-onset epilepsy following meningioma peritumoral brain edema and resection. A diagnosis of AE should be considered in patients presenting with stroke-like symptoms if the magnetic resonance imaging abnormality does not match a known vascular territory. Early and correct diagnosis is crucial because immunotherapy is usually effective for this disease., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

The direct C-H activation without directing groups can realize the para -selectivity, which is a powerful and concise approach for functionalization of arenes. Utilizing the strategy, a C5-olefination of methyleneindolinones has been successfully developed by palladium-catalyzed direct C-H activation, which provides an expeditious access to 5-vinylindolin-2-ones with high regioselectivity. The protocol is distinguished by a mild reaction system avoiding ligand and high temperature. The kinetic isotope experiments indicate that the C-H bond cleavage is the rate-limiting step.

Precision mitigation of COVID-19 is in pressing need for postpandemic time with the absence of pharmaceutical interventions. In this study, the effectiveness and cost of digital contact tracing (DCT) technology-based on-campus mitigation strategy are studied through epidemic simulations using high-resolution empirical contact networks of teachers and students. Compared with traditional class, grade, and school closure strategies, the DCT-based strategy offers a practical yet much more efficient way of mitigating COVID-19 spreading in the crowded campus. Specifically, the strategy based on DCT can achieve the same level of disease control as rigid school suspensions but with significantly fewer students quarantined. We further explore the necessary conditions to ensure the effectiveness of DCT-based strategy and auxiliary strategies to enhance mitigation effectiveness and make the following recommendation: social distancing should be implemented along with DCT, the adoption rate of DCT devices should be assured, and swift virus tests should be carried out to discover asymptomatic infections and stop their subsequent transmissions. We also argue that primary schools have higher disease transmission risks than high schools and, thereby, should be alerted when considering reopenings.

Background: Mediastinal neuroblastoma (NB) can invade the spinal canal and result in spinal cord compression. Some patients go on to develop severe spinal deformities after decompression of the spinal cord. The optimal therapeutic strategy for mediastinal NB with intraspinal extension is still unclear. Our study is to assess the therapeutic strategies for such patients., Methods: A total of 77 patients suffered mediastinal tumors with intraspinal extension between March 2015 and Aug 2019 were enrolled in the study. According to the primary therapy, NB were classified into 4 groups: chemotherapy, video-assisted thoracoscopic surgery (VATS)/thoracotomy, neurosurgical decompression, and a combined thoracic-neurosurgical approach. Clinical features, including patient demographics, neurologic recovery and survival rate, were assessed., Results: Among the 77 patients suffered mediastinal tumors with intraspinal extension, neurological symptoms were present in 44 patients. Neurological deficits improved in 76.5% of patients who underwent neurosurgical intervention and 50% of the other patients (P=0.094). Compression manifestations of ≤4 weeks duration showed an improved outcome compared to a longer compression time, with complete recovery of neurological function in 60% of patients versus 28.6% for patients with a longer symptom duration (P=0.04). NB constituted 49.4% of the 77 patients. An overall survival rate of 90.0%±9.5% was achieved for patients in the combined thoracic-neurosurgical group, 59.5%±15.0% in the thoracotomy group, 40.0%±29.7% in laminectomy group, and 37.0%±20.2% in the chemotherapy group. Complete regression of the tumor was demonstrated in 80% of combined group, which was greater than that of patients in the other groups (P=0.001)., Conclusions: Neurological recovery was correlated with the type of initial treatment and the duration of neurological symptoms. Mediastinal NB with intraspinal extension can be effectively managed with a combined neurosurgical and thoracic surgical approach., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tp-20-268). The authors have no conflicts of interest to declare., (2021 Translational Pediatrics. All rights reserved.)

Somatostatin (SST) and somatostatin receptors (SSTRs) play an important role in the brain and gastrointestinal (GI) system. SST is produced in various organs and cells, and the inhibitory function of somatostatin-containing cells is involved in a range of physiological functions and pathological modifications. The GI system is the largest endocrine organ for digestion and absorption, SST-endocrine cells and neurons in the GI system are a critical effecter to maintain homeostasis via SSTRs 1-5 and co-receptors, while SST-SSTRs are involved in chemo-sensory, mucus, and hormone secretion, motility, inflammation response, itch, and pain via the autocrine, paracrine, endocrine, and exoendocrine pathways. It is also a power inhibitor for tumor cell proliferation, severe inflammation, and post-operation complications, and is a first-line anti-cancer drug in clinical practice. This mini review focuses on the current function of producing SST endocrine cells and local neurons SST-SSTRs in the GI system, discusses new development prognostic markers, phosphate-specific antibodies, and molecular imaging emerging in diagnostics and therapy, and summarizes the mechanism of the SST family in basic research and clinical practice. Understanding of endocrines and neuroendocrines in SST-SSTRs in GI will provide an insight into advanced medicine in basic and clinical research., 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 © 2021 Shamsi, Chatoo, Xu, Xu and Chen.)

The 2019 coronavirus disease (COVID-19) is pseudonymously linked to more than 100 million cases in the world as of January 2021. High-quality data are needed but lacking in the understanding of and fighting against COVID-19. We provide a complete and updating hand-coded line-list dataset containing detailed information of the cases in China and outside the epicenter in Hubei province. The data are extracted from public disclosures by local health authorities, starting from January 19. This dataset contains a very rich set of features for the characterization of COVID-19's epidemiological properties, including individual cases' demographic information, travel history, potential virus exposure scenario, contacts with known infections, and timelines of symptom onset, quarantine, infection confirmation, and hospitalization. These cases can be considered the baseline COVID-19 transmissibility under extreme mitigation measures, and therefore, a reference for comparative scientific investigation and public policymaking.

Four new 3,4-secocycloartane triterpenoids, pseudolactones A-D (1-4), were isolated from the ethanol extract of the cones of Pseudol arixamabilis. Their structures were established by extensive 1D- and 2D-NMR experiments. The cones of P. arixamabilis are enriched in the ring-expanded or cleaved cycloartane triterpenoids. This work provides new insight into cycloartane triterpenoids from the cones of P. arixamabilis.

Background: Knowledge on the epidemiological features and transmission patterns of novel coronavirus disease (COVID-19) is accumulating. Detailed line-list data with household settings can advance the understanding of COVID-19 transmission dynamics., Methods: A unique database with detailed demographic characteristics, travel history, social relationships, and epidemiological timelines for 1407 transmission pairs that formed 643 transmission clusters in mainland China was reconstructed from 9120 COVID-19 confirmed cases reported during 15 January-29 February 2020. Statistical model fittings were used to identify the superspreading events and estimate serial interval distributions. Age- and sex-stratified hazards of infection were estimated for household vs nonhousehold transmissions., Results: There were 34 primary cases identified as superspreaders, with 5 superspreading events occurred within households. Mean and standard deviation of serial intervals were estimated as 5.0 (95% credible interval [CrI], 4.4-5.5) days and 5.2 (95% CrI, 4.9-5.7) days for household transmissions and 5.2 (95% CrI, 4.6-5.8) and 5.3 (95% CrI, 4.9-5.7) days for nonhousehold transmissions, respectively. The hazard of being infected outside of households is higher for people aged 18-64 years, whereas hazard of being infected within households is higher for young and old people., Conclusions: Nonnegligible frequency of superspreading events, short serial intervals, and a higher risk of being infected outside of households for male people of working age indicate a significant barrier to the identification and management of COVID-19 cases, which requires enhanced nonpharmaceutical interventions to mitigate this pandemic., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Glioblastoma (GBM) is the most malignant primary brain tumor in adults. Due to its invasive nature, it cannot be thoroughly eliminated. WD repeat domain 12 (WDR12) processes the 32S precursor rRNA but cannot affect the synthesis of the 45S/47S primary transcript. In this study, we found that WDR12 is highly expressed in GBM according to the analysis results of mRNA expression by The Cancer Genome Atlas database. The high expression level of WDR12 is dramatically related to shorter overall survival and reduced disease-free survival. Next, we knocked down WDR12 and found that knockdown of WDR12 promoted the apoptosis and inhibited the proliferation by cell biology experiments. Differential expression genes in gene-chip revealed that WDR12 knockdown mainly inhibited cell cycle. Finally, we also found that WDR12 is associated with PLK1 and EZH2 in cell proliferation of GBM. Resumptively, this report showed a possible evidence that WDR12 drove malignant behavior of GBM, whose expression may present a neoteric independent prognostic biomarker in GBM., (© 2020 Wiley Periodicals, Inc.)

Studies of novel coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have reported varying estimates of epidemiological parameters, including serial interval distributions-i.e., the time between illness onset in successive cases in a transmission chain-and reproduction numbers. By compiling a line-list database of transmission pairs in mainland China, we show that mean serial intervals of COVID-19 shortened substantially from 7.8 to 2.6 days within a month (9 January to 13 February 2020). This change was driven by enhanced nonpharmaceutical interventions, particularly case isolation. We also show that using real-time estimation of serial intervals allowing for variation over time provides more accurate estimates of reproduction numbers than using conventionally fixed serial interval distributions. These findings could improve our ability to assess transmission dynamics, forecast future incidence, and estimate the impact of control measures., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: Although a varicella vaccine has been available in China since 1998 in the private sector, varicella outbreaks and breakthrough varicella (BV) still occur. In 2018, four varicella outbreaks with high BV rate sequentially occurred in four schools in Lu'an, sparking local public health authority's concerns on the varicella vaccine. Therefore, we conducted this investigation to evaluate varicella vaccine effectiveness (VE), characterize BV, and detect potential risk factors associated with BV., Methods: This was a three-stage study. First, a retrospective cohort study was done in each school to estimate the VEs of varicella vaccine  during outbreaks. Second, a descriptive epidemiological method was used to describe the characteristics of the four outbreaks and to compare the clinical characteristics between the BV cases and unvaccinated varicella cases. To identify the risk factors associated with BV, we conducted an unmatched case-control study in the third stage of the study., Results: A total of 199 cases were identified among four outbreaks, and the overall attack rate was 14%. Of 1203 students with available vaccination information, 822 (68%) were vaccinated at least once. The overall VEs among four outbreaks ranged from 19% to 69%, whereas the VE against moderate or severe varicella ranged from 74% to 90%. Compared with unvaccinated varicella cases, the moderate or severe varicella ( p < .001) and fever ( p = .029) in the BV group were less common. Besides, BV cases had a shorter duration of disease ( p = .007). Children vaccinated more than six years before the outbreak had a higher risk of developing BV compared with those vaccinated within the past six years (OR = 2.4, 95% CI: 1.2-4.8). The risk of developing BV differed by the exposure intensity. Compared with the presence of three or fewer varicella cases in the same class, the OR was 7.8 (95% CI: 3.6-16.9) for four to nine cases in the same class and 25.2 (95% CI: 13.5 -47.2) for that of 10 or more cases., Conclusions: The overall VE was insufficient to protect varicella infection, and the VE for moderate or severe varicella was only moderate. The manifestations of BV cases were generally milder than those seen in natural varicella infection. The time since vaccination and the intensity of exposure are risk factors for developing BV during an outbreak.

A transition-metal-free double addition/double rearrangement domino reaction affording CF3-substituted pyrimidines was developed, which enables the one-pot construction of five new bonds, namely three C-C bonds and two C-N bonds. The keys to achieve this highly efficient reaction include the delicate design of the bis-nucleophiles in situ generated from the dimerization of alkyl nitriles and the use of trifluoroacetimidoyl nitriles containing C[double bond, length as m-dash]N, C[triple bond, length as m-dash]N, and CF3 groups as the reactant. The mechanistic studies by the experiments and DFT calculations reveal that the transformation involves two addition and two unprecedented rearrangement processes.

Seven oleanane-type triterpenoid saponins, tunicosaponins B-D (1-3), F-I (4-7), along with eight known triterpenoid saponins (8-15), were isolated from the roots of Psammosilene tunicoides. The structures of compounds 1-7 were determined by comprehensive spectroscopic analysis, including 1D and 2D NMR techniques, mass spectrometry and chemical methods. Triterpene glycosides have been considered as major active constituents of P. tunicoides. This work provides a more complete insight into the saponin constituents of P. tunicoides., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2020. Published by Elsevier B.V.)