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Sestrin2 is a highly conserved stress-inducible protein, acting as a crucial part in regulating homeostasis in response to various stress conditions in the cell. However, the role of Sestrin2 in regulating cell apoptosis related to endoplasmic reticulum (ER) has not been fully investigated. Our study presented here aims to reveal the effect of Sestrin2 in tunicamycin (TM)-induced cell apoptosis related to ER stress and its underlying molecular mechanisms. The results demonstrated that Sestrin2 expression was significantly upregulated correlated with ER stress responses in TM treated HepG2 cells. Sestrin2 overexpression obviously alleviated ER stress with the determination of ER stress-related proteins expression. In addition, Sestrin2 overexpression inhibited cell apoptosis with the examination of apoptosis-related proteins and TUNEL assay. However, Sestrin2 knockdown further promoted the ER stress-mediated cell apoptosis. The further mechanistic study revealed that Sestrin2 overexpression inhibited TM-induced mTOR pathway activation. Taken together, our current study indicated that Sestrin2 overexpression ameliorates ER stress-induced apoptosis via inhibiting mTOR pathway in HepG2 cells.

Microglia are resident immune cells in the brain and are closely associated with central nervous system inflammation and neurodegenerative diseases. It is known that mammalian target of rapamycin (mTOR) pathway plays an important role in the polarization of microglia. Castor1 has been identified as the cytosolic arginine sensor for the mTOR complex 1 (mTORC1) pathway, but the role of Castor1 in microglial polarization is still unknown. The purpose of this study was to explore the regulatory effect of Castor1 on microglial polarization and the underlying mechanism. The results demonstrated that Castor1 expression was significantly decreased in lipopolysaccharides (LPS) and interferon (IFN)-γ treated microglia. Castor1 overexpression inhibited the microglia M1 polarization by reducing the expression of M1 related markers. However, the expression of M2-related genes was promoted when Castor1 was overexpressed in IL-4 treated microglia. Mechanistically, Castor1 overexpression inhibited the activation of mTOR signaling pathway. In addition, after treatment with the mTOR activator MHY1485, the inhibitory effect of Castor1 overexpression on M1 polarization was attenuated, indicating that the regulation effects of Castor1 on M1 polarization was dependent on its inhibition of mTOR pathway. We propose that Castor1-mTOR signaling pathway could be considered as a potential target for treatment and intervention of central nervous system-related diseases by regulating microglia polarization.

Children are the future of the world, but their health and future are facing great uncertainty because of the coronavirus disease 2019 (COVID-19) pandemic. In order to improve the management of children with COVID-19, an international, multidisciplinary panel of experts developed a rapid advice guideline at the beginning of the outbreak of COVID-19 in 2020. After publishing the first version of the rapid advice guideline, the panel has updated the guideline by including additional stakeholders in the panel and a comprehensive search of the latest evidence. All recommendations were supported by systematic reviews and graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Expert judgment was used to develop good practice statements supplementary to the graded evidence-based recommendations. The updated guideline comprises nine recommendations and one good practice statement. It focuses on the key recommendations pertinent to the following issues: identification of prognostic factors for death or pediatric intensive care unit admission; the use of remdesivir, systemic glucocorticoids and antipyretics, intravenous immunoglobulin (IVIG) for multisystem inflammatory syndrome in children, and high-flow oxygen by nasal cannula or non-invasive ventilation for acute hypoxemic respiratory failure; breastfeeding; vaccination; and the management of pediatric mental health.This updated evidence-based guideline intends to provide clinicians, pediatricians, patients and other stakeholders with evidence-based recommendations for the prevention and management of COVID-19 in children and adolescents. Larger studies with longer follow-up to determine the effectiveness and safety of systemic glucocorticoids, IVIG, noninvasive ventilation, and the vaccines for COVID-19 in children and adolescents are encouraged.• Several clinical practice guidelines for children with COVID-19 have been developed, but only few of them have been recently updated. • We developed an evidence-based guideline at the beginning of the COVID-19 outbreak and have now updated it based on the results of a comprehensive search of the latest evidence.• The updated guideline provides key recommendations pertinent to the following issues: identification of prognostic factors for death or pediatric intensive care unit admission; the use of remdesivir, systemic glucocorticoids and antipyretics, intravenous immunoglobulin for multisystem inflammatory syndrome in children, and high-flow oxygen by nasal cannula or non-invasive ventilation for acute hypoxemic respiratory failure; breastfeeding; vaccination; and the management of pediatric mental health.

Background Mycoplasma pneumoniae (M. pneumoniae) is an important pathogen of community-acquired pneumonia in children. However, prior to this study, there was a lack of research on the genotypes and macrolide resistance monitoring of M. pneumoniae in Wuhan. The factors contributing to the severity of illness caused by M. pneumoniaeinfection are still under investigation. We aimed to evaluate the clinical manifestations, genotypes, macrolide resistance, respiratory microenvironment, and their relationship with the severity of illness in children with M. pneumoniaepneumonia in Wuhan. Results Among 1,259 clinical samples, 461 samples were positive for M. pneumoniae via qPCR. We successfully identified the P1 genotypes of 127 samples based on metagenomic and Sanger sequencing, with P1-type 1 (113/127, 88.98%) being the dominant genotype. In addition, we identified the MLST genotypes of 67 samples, with ST-3 being the most common (60/67, 89.6%), followed by ST-14 (5/67, 7.4%) and ST-7 (2/67, 3%). No significant difference in pathogenicity was observed among different genotypes. The macrolide resistance rate of M. pneumoniaeisolates was 96% (48/50) and all mutations were A2063G in domain V of 23S rRNA gene. There was no significant difference between the upper respiratory microbiome of patients with mild and severe symptoms. The pan-genome analysis revealed that the genome of M. pneumoniae is highly conserved, with the core genome comprising 79% of the total genome length. In addition, the initial serological test cannot accurately diagnose M. pneumoniae infection. qPCR is suitable for detecting M. pneumoniaeinfection, while IgM titers greater than 1:160 can be used as a predictor of severity. Conclusions This study is the first to characterize the epidemic and genomic features of M. pneumoniae in Wuhan after the COVID-19 outbreak in 2020, which provides a scientific data basis for monitoring and infection prevention and control of M. pneumoniae in the post-pandemic era.

Background The objective of this study was to examine the relationship of mental health status between self-poisoning suicide patients and their family members, and it also sought to identify potential patient’s risk and parental factors for the prediction of suicide attempt, anxiety, and depression. Methods In this study, 151 poisoned patients were prospectively included, and they were matched 1:1 with 151 family members. We gathered information on patient’s and their matched family member’s demographics, lifestyle choices, mental health status, level of intimacy, and history of psychiatry disease. The relationship of patient’s and their family member’s mental health state was investigated using a correlation matrix. Multivariable analyses (multiple logistic regression) were conducted among patients and their matched family members, to identify potential risk factors for self-poisoning suicide, anxiety, and depression. Results Of the total patients, 67.55% (102/151) attempted self-poisoning suicide. Poisoned patients had more severe anxiety and depression symptoms than their matched family members, and this difference was even more pronounced among patients with self-poisoning suicide. Generalized anxiety disorder-7 (GAD-7) score for family members was significantly and favorably correlated with patient’s GAD-7 score after eliminating non-suicide patients and their matched family members. The patient health questionnaire-9 (PHQ-9) score showed a similar pattern, and the family member’s PHQ-9 score was strongly and favorably associated with patient’s PHQ-9 and Beck hopelessness scale-20 (BHS-20) score. Multivariable analysis showed that married marital status (P = 0.038), quitting smoking (P = 0.003), sedentary time of 1 to 6 h (P = 0.013), and participation in a sports more than five times per week (P = 0.046) were all significantly associated with a lower risk of suicide by self-poisoning, while a more serious anxiety state (P = 0.001) was significantly associated with a higher risk of self-poisoning suicide. Multivariable analysis demonstrated that, specifically among self-poisoning suicide patients, married marital status (P = 0.011) and no history of psychiatry disease (P P = 0.004), a sedentary time of 1 to 3 h (P = 0.022), and a higher monthly income (P = 0.027) were significant contributors to anxiety. The propensity of additional family-matched characteristics to predict patient’s suicidality, anxiety, and depression was also examined. Conclusions Self-poisoning suicide patients have severe mental health issues. Patients who self-poison have a close connection to their family member’s mental health, particularly their levels of anxiety and depression. According to the findings, being married and adopting healthy lifestyle habits, such as quitting smoking and drinking, increasing their physical activity levels, and managing their idle time, are able to help patients with mental health concerns and even suicidal thoughts.

College English follow-up courses are an important part of “University English Curriculum Teaching Requirements” and college English curriculum reform, and its purpose is to meet the individual needs of learners at different levels. “College English Curriculum Teaching Requirements” pointed out “Each school should design its own college English curriculum system according to the curriculum requirements and the college English teaching objectives of the school, while ensuring the improvement of students’ language proficiency, it should be conducive to students’ personalized learning. to meet their respective development requirements.” With the rise and development of computer technology, human society has ushered in the fifth information technology revolution. In just a few decades, people’s life and production methods have undergone tremendous changes. Computer information technology has been widely used in military, medical, commercial, education, and industrial fields. Multimedia-assisted teaching has incomparable advantages in these situations. The use of network, computer, and multimedia has made the English classroom teaching methods changed essentially. Due to the huge storage capacity of the computer, it can use graphics, sound, and animation to express, organize, and store the corresponding text knowledge materials, so that the sound, image, and text can truly coexist, achieving an effective increase in the amount of information dissemination and enhancing stimulus intensity of information so as to make the students’ enthusiasm for learning knowledge improved. It is precisely because of the powerful information dissemination ability, information processing ability, and convenient and fast interactive form of multimedia itself that it can be used in teaching to enrich the way of classroom teaching activities and make classroom teaching methods no longer single, which can make students better complete the transition from concrete image thinking to abstract logical thinking. The smooth development of college English follow-up courses will continuously improve the English quality of our talents. Learners of different majors have different needs for follow-up college English teaching. Only when students of different majors adopt different teaching courses can they fully reflect the individuality and suitability of the courses. In order to understand the specific needs and views of students of different majors on the courses, students of different majors are made to adopt different teaching courses to get personalized and appropriate learning experience. We distributed questionnaires to senior students at a certain university and adopted Dudley-Evans and St John’s needs analysis method for the survey results. It is found that liberal arts students are looking forward to the language application and language skills modules, and their satisfaction with these two modules is as high as 86.23%. The science students and engineering students are more satisfied with the two modules of professional English and language application. Among them, the satisfaction of science students on these two modules is 78.63%, and the satisfaction of engineering students is as high as 92.38%. Students of different majors have a positive attitude towards English follow-up courses, but there is a big difference between the courses offered by universities and the teaching mode. For example, 85.62% of liberal arts students are satisfied with the recognition of the course mode, and only 14.38% are dissatisfied; 66.3% of science students are satisfied with the curriculum model, 33.7% are dissatisfied; 66.45% of engineering students are satisfied with the curriculum, and 33.55% are dissatisfied.

Paraquat is a quaternary ammonium herbicide with an excellent herbicidal effect but is highly toxic to human and animals. Although prohibited by many countries, paraquat intoxication occurred occasionally and caused severe consequences. Rapid and accurate determination of paraquat concentration in intoxication samples is urgently needed in the clinic to promptly evaluate the prognosis of poisoning patients. Here we report an internal standard surface-enhanced Raman spectroscopy (IS-SERS) quantification method on paraquat in mouse plasma and lung tissues for the first time. One measurement per sample was fulfilled within 10 s via this IS-SERS method. Paraquat had good linearity in the range of 1 ~ 500 μg/L (plasma sample) and 1 ~ 100 μg/g (lung sample), with the LOD and LOQ of 0.5 μg/L and 0.1 μg/g (plasma sample), and 5 μg/L and 1 μg/g (lung sample), respectively. This IS-SERS method was validated according to the international guidelines and applied to a quantitative determination and the toxicokinetics on paraquat in mouse plasma and lung tissues. The results indicated that paraquat had a fast absorption rate and a slow elimination rate in mouse plasma and lung tissues. Paraquat was prone to accumulate in target organs after entering the blood. It also proved its good practical applicability in one clinical intoxication sample. Meanwhile, we unveiled an underestimation of free paraquat amount towards common biological sample pretreatment, a certain amount of paraquat bound to components with molecular weight less than 30 kDa in the plasma; we hope it could provide some interesting information for possible clinic treatment.

Schematic diagram of HCR amplification strategy for the detection of miRNAs. (A) The preparation process of AuNHs array. (B) Synthesis of SERS probes (C) HCR process and SERS detection of miR-31 and miR-21.

The prenylation of phenolic substrates promoted by magnesium dicarboxylates was developed. An investigation of the scope demonstrated that substrates with electron-donating group(s) gave better yields than those with electron-withdrawing group(s). Although the conversions of all substrates were higher in MeCN than in DMF, DMF was still the favorable solvent for polyphenolic substrates since MeCN would cause the generation of cyclized by-products (6) and reduce the yield of 3. The regio-selectivity of

Transforming growth factor-beta (TGF

In this work, a highly specific and sensitive method for the detection of dual miRNAs was successfully developed by a hybridization chain reaction (HCR) amplification coupled with surface-enhanced Raman scattering (SERS) on Au-Ag hollow nanoparticles (Au-Ag HNPs) and a gold nanohexagon (AuNH) array. Two Raman reporter-labelled and hairpin DNA-modified Au-Ag HNPs acted as SERS probes (Au-Ag HNPs@4-MBA@HP

Colchicine poisoning is complicated and has a high mortality rate. The aim of this study was to identify the pathogenic characteristics of colchicine poisoning cases and to propose a comprehensive treatment procedure. A total of 43 patients were divided into survival (n = 32) and death groups (n = 11) according to prognosis. The clinical data (basic information, clinical manifestations, laboratory tests, examination results, therapeutic schedule, response evaluation, and prognosis) were analyzed, and the comprehensive treatment was proposed. The ingestion doses were ≤0.5, 0.5–0.8, and ≥0.8 mg/kg, and the survival rates were 100, 83.33, and 28.60%. The causes of death were cardiovascular and bone marrow hematopoietic failures. We found that the order of organ damage was digestive tract, coagulation, muscle, heart, hematopoietic, lung, liver, and kidney, while the recovery order was digestive tract, coagulation, heart, hematopoietic, lung, muscle, kidney, and liver. Different doses of recombinant human granulocyte colony-stimulating factor and recombinant human thrombopoietin can shorten the severity and duration of neutropenia and thrombocytopenia. Plasma exchange combined with continuous veno-venous hemodialysis filtration treatment can increase survival time. The prognosis is positively correlated with the dose. Early removal of toxicants from the digestive tract and blood is essential. It is vital to give comprehensive treatment of multiple organ injuries， include the use of recombinant human granulocyte colony-stimulating factor, recombinant human thrombopoietin, plasma exchange, and continuous veno-venous hemodialysis filtration.

[Image: see text] In this paper, we report the design, synthesis, and biological evaluation of the first selective bromodomain and extra-terminal domain (BET) BD1 bromodomains of the PET radiotracer [(18)F]PB006. The standard compound PB006 showed high affinity and good selectivity toward BRD4 BD1 (K(d) = 100 nM and 29-fold selectively for BD1 over BD2) in an in vitro binding assay. PET imaging experiments in rodents were performed to evaluate the bioactivity of [(18)F]PB006 in vivo. A biodistribution study of [(18)F]PB006 in mice revealed high radiotracer uptake in peripheral tissues, such as liver and kidney, and moderate radiotracer uptake in the brain. Further blocking studies demonstrated the significant radioactivity decreasing (20–30% reduction compared with baseline) by pretreating unlabeled PB006 and JQ1, suggesting the high binding selectivity and specificity of [(18)F]PB006. Our study indicated that [(18)F]PB006 is a potent PET probe selectively targeting BET BD1, and further structural optimization of the radiotracer is still required to improve brain uptake to support neuroepigenetic imaging.

Background Children and older adults with coronavirus disease 2019 (COVID-19) display a distinct spectrum of disease severity yet the risk factors aren’t well understood. We sought to examine the expression pattern of angiotensin-converting enzyme 2 (ACE2), the cell-entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the role of lung progenitor cells in children and older patients. Methods We retrospectively analyzed clinical features in a cohort of 299 patients with COVID-19. The expression and distribution of ACE2 and lung progenitor cells were systematically examined using a combination of public single-cell RNA-seq data sets, lung biopsies, and ex vivo infection of lung tissues with SARS-CoV-2 pseudovirus in children and older adults. We also followed up patients who had recovered from COVID-19. Results Compared with children, older patients (>50 years.) were more likely to develop into serious pneumonia with reduced lymphocytes and aberrant inflammatory response (P = .001). The expression level of ACE2 and lung progenitor cell markers were generally decreased in older patients. Notably, ACE2 positive cells were mainly distributed in the alveolar region, including SFTPC positive cells, but rarely in airway regions in the older adults (P < .01). The follow-up of discharged patients revealed a prolonged recovery from pneumonia in the older (P < .025). Conclusions Compared to children, ACE2 positive cells are generally decreased in older adults and mainly presented in the lower pulmonary tract. The lung progenitor cells are also decreased. These risk factors may impact disease severity and recovery from pneumonia caused by SARS-Cov-2 infection in older patients.

MicroRNAs (miRNAs) are key players in human hepatocellular carcinoma (HCC) tumorigenesis. Therefore, small molecules targeting components of miRNA biogenesis may provide new therapeutic means for HCC treatment. By a high-throughput screening and structural simplification, we identified a small molecule, CIB-3b, which suppresses the growth and metastasis of HCC

Microglia are resident immune cells in the brain and are closely associated with central nervous system inflammation and neurodegenerative diseases. It is known that mTOR pathway plays an important role in the polarization of microglia. Castor1 has been identified as the cytosolic arginine sensor for the mTORC1 pathway, but the role of Castor1 in microglial polarization is still unknown. The purpose of this study was to explore the regulatory effect of Castor1 on microglial polarization and the underlying mechanism. The results demonstrated that Castor1 expression was significantly decreased in LPS and IFNγ treated microglia. Castor1 overexpression inhibited the microglia M1 polarization by reducing the expression of M1 related markers. However, microglia M2 polarization was promoted when Castor1 was overexpressed in IL-4 treated microglia. Mechanistically, Castor1 overexpression inhibited the activation of mTOR signaling pathway. In addition, after treatment with the mTOR activator MHY1485, the inhibitory effect of Castor1 overexpression on M1 polarization was attenuated, indicating that the regulation effects of Castor1 on M1 polarization was dependent on its inhibition of mTOR pathway. We propose that Castor1-mTOR signaling pathway could be considered as a potential target for treatment and intervention of central nervous system-related diseases by regulating microglia polarization.

Colchicine poisoning is complicated and has a high mortality rate. The aim of this study was to identify the pathogenic characteristics of colchicine poisoning cases and to propose a comprehensive treatment procedure. A total of 43 patients were divided into survival (

BACKGROUND: The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has made widespread impact recently. We aim to investigate the clinical characteristics of COVID-19 children with different severities and allergic status. METHODS: Data extracted from the electronic medical records, including demographics, clinical manifestations, comorbidities, laboratory and immunological results, and radiological images of 182 hospitalized COVID-19 children, were summarized and analyzed. RESULTS: The median age was 6 years, ranging from 3 days to 15 years, and there were more boys (male-female ratio about 2:1) within the studied 182 patients. Most of the children were infected by family members. Fever (43.4%) and dry cough (44.5%) were common symptoms, and gastrointestinal manifestations accounted for 11.0%, including diarrhea, abdominal discomfort, and vomiting. 71.4% had abnormal chest computed tomography (CT) scan images, and typical signs of pneumonia were ground-glass opacity and local patchy shadowing on admission. Laboratory results were mostly within normal ranges, and only a small ratio of lymphopenia (3.9%) and eosinopenia (29.5%) were observed. The majority (97.8%) of infected children were not severe, and 24 (13.2%) of them had asymptomatic infections. Compared to children without pneumonia (manifested as asymptomatic and acute upper respiratory infection), children with pneumonia were associated with higher percentages of the comorbidity history, symptoms of fever and cough, and increased levels of serum procalcitonin, alkaline phosphatase, and serum interleukins (IL)-2, IL-4, IL-6, IL-10, and TNF-α. There were no differences in treatments, duration of hospitalization, time from first positive to first negative nucleic acid testing, and outcomes between children with mild pneumonia and without pneumonia. All the hospitalized COVID-19 children had recovered except one death due to intussusception and sepsis. In 43 allergic children with COVID-19, allergic rhinitis (83.7%) was the major disease, followed by drug allergy, atopic dermatitis, food allergy, and asthma. Demographics and clinical features were not significantly different between allergic and nonallergic groups. Allergic patients showed less increase in acute phase reactants, procalcitonin, D-dimer, and aspartate aminotransferase levels compared with all patients. Immunological profiles including circulating T, B, and NK lymphocyte subsets, total immunoglobulin and complement levels, and serum cytokines did not show any difference in allergic and pneumonia groups. Neither eosinophil counts nor serum total immunoglobulin E (IgE) levels showed a significant correlation with other immunological measures, such as other immunoglobulins, complements, lymphocyte subset numbers, and serum cytokine levels. CONCLUSION: Pediatric COVID-19 patients tended to have a mild clinical course. Patients with pneumonia had higher proportion of fever and cough and increased inflammatory biomarkers than those without pneumonia. There was no difference between allergic and nonallergic COVID-19 children in disease incidence, clinical features, and laboratory and immunological findings. Allergy was not a risk factor for developing and severity of SARS-CoV-2 infection and hardly influenced the disease course of COVID-19 in children.

ObjectivesTo investigate the clinical value of detecting anti–mutated citrullinated vimentin (anti-MCV), anti-citrullinated peptide (anti-CCP), red-blood-cell distribution width (RDW), and 25-hydroxyvitamin D (25-[OH]D) in the diagnosis of rheumatoid arthritis (RA).MethodsWe enrolled 119 patients with RA, 114 control individuals without RA (disease controls), and 40 healthy controls in our study (Han Chinese). Anti-CCP and anti-MCV were detected by enzyme-linked immunosorbent assay (ELISA), 25-(OH)D was detected by electrochemical luminescence, and RDW was calculated by erythrocyte parameters detected via the electric resistance method.ResultsThe serum levels of anti-CCP and anti-MCV in RA were higher than those in disease controls and healthy controls (P ConclusionsAnti-CCP and anti-MCV are ideal indices for RA diagnosis. Also, in combination with RDW and 25-(OH)D, the diagnostic level will be improved, as well as the sensitivity and specificity, which is significant for the differential diagnosis of RA.

The pandemic due to a novel coronavirus has been sweeping across different regions of the globe since January 2020. Early reports of this infection due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) consisted of mostly adult patients. As the outbreak spreads rapidly beyond the epicentre of Wuhan, it becomes clear that infants and children of all ages are susceptible to this infection. In China, there have been more than 1200 paediatric cases. Most paediatric patients acquire the infection through household contact with infected adults. The disease in children is usually self-limiting and most infected children will recover uneventfully within 7–10 days. Other than symptoms of the respiratory tract, many children may present with gastrointestinal symptoms. Older children are more likely to have asymptomatic infection. Although deaths related to SARS-CoV-2 are rarely reported in the paediatric age group, young children and those with underlying medical conditions are more likely to develop severe illness. Only a small fraction of neonates born to infected mother would acquire the virus by vertical transmission. Because a large proportion of children and adolescents may have asymptomatic or mildly symptomatic infection, children are likely to play an important role in community transmission of this infection. Screening of children who have a definitive contact history will facilitate early diagnosis and isolation of all infected children. This review summarises the lessons learned in China with regard to the current understanding of SARS-CoV-2 infection in the paediatric population.

Introduction Bromodomain and extra-terminal domain (BET) family proteins play a vital role in the epigenetic regulation process by interacting with acetylated lysine (Ac-K) residues in histones. BET inhibitors have become promising candidates to treat various diseases through the inhibition of the interaction between BET bromodomains and Ac-K of histone tails. With a molecular imaging probe, noninvasive imaging such as positron emission tomography (PET) can visualize the distribution and roles of BET family proteins in vivo and enlighten our understanding of BET protein function in both healthy and diseased tissue. Methods We radiolabeled the potent BET inhibitor INCB054329 by N-methylation to make [11C]PB003 as a BET PET radiotracer. The bioactivity evaluation of unlabeled PB003 in vitro was performed to confirm its binding affinity for BRDs, then the PET/CT imaging in rodents was performed to evaluate the bioactivity of [11C]PB003 in vivo. Results In our in vitro evaluation, PB003 showed a high BET binding affinity for BRDs (Kd = 2 nM, 1.2 nM, and 1.2 nM for BRD2, BRD3, and BRD4, respectively). In vivo PET/CT imaging demonstrated that [11C]PB003 has favorable uptake with appropriate kinetics and distributions in main peripheral organs. Besides, the blockade of [11C]PB003 binding was found in our blocking study which indicated the specificity of [11C]PB003. However, the BBB penetration and brain uptake of [11C]PB003 was limited, with only a maximum 0.2% injected dose/g at ~2 min post-injection. Conclusion The imaging results in rodents in vivo demonstrate that [11C]PB003 binds to BET with high selectivity and specificity and has favorable uptake in peripheral organs. However, the low brain uptake of [11C]PB003 limits the visualization of brain regions indicating the efforts are still needed to discover the new BET imaging probes for brain visualization.

In the early February, 2020, we called up an experts' committee with more than 30 Chinese experts from 11 national medical academic organizations to formulate the first edition of consensus statement on diagnosis, treatment and prevention of coronavirus disease 2019 (COVID-19) in children, which has been published in this journal. With accumulated experiences in the diagnosis and treatment of COVID-19 in children, we have updated the consensus statement and released the second edition recently. The current version in English is a condensed version of the second edition of consensus statement on diagnosis, treatment and prevention of COVID-19 in children. In the current version, diagnosis and treatement criteria have been optimized, and early identification of severe and critical cases is highlighted. The early warning indicators for severe pediatric cases have been summarized which is utmost important for clinical practice. This version of experts consensus will be valuable for better prevention, diagnosis and treatment of COVID-19 in children worldwide.

Since December 2019, COVID-19 has occurred unexpectedly and emerged as a health problem worldwide. Despite the rapidly increasing number of cases in subsequent weeks, the clinical characteristics of pediatric cases are rarely described. A cross-sectional multicenter study was carried out in 10 hospitals across Hubei province. A total of 25 confirmed pediatric cases of COVID-19 were collected. The demographic data, epidemiological history, underlying diseases, clinical manifestations, laboratory and radiological data, treatments, and outcomes were analyzed. Of 25 hospitalized patients with COVID-19, the boy to girl ratio was 1.27:1. The median age was 3 years. COVID-19 cases in children aged

In this work, a new Sr(II)-based coordination polymer (CP) with the chemical formula of [Sr3(L)2(H2O)4] (1) (H3L = 4'-hydroxy-[1,1'-biphenyl]-3,3',5-tricarboxylic acid) has been successfull...

Acute inflammatory diseases, such as sepsis, are life-threatening illnesses. Regulating the α7 nicotinic acetylcholine receptor (α7 nAchR)-mediated signaling may be a promising strategy to treat sepsis. Diarylheptanoids have long been found to exhibit anti-inflammatory properties. However, the possible mechanism of diarylheptanoids has rarely been investigated. In this study, we isolated and synthesized 49 diarylheptanoids and analogues and evaluated their anti-inflammatory activities. Among them, compounds 28 and 40 markedly blocked lipopolysaccharide (LPS)-induced production of nitric oxide (NO), interleukin-1β (IL-1β) and interleukin-6 in murine RAW264.7 cells. Furthermore, compounds 28 and 40 also effectively attenuated LPS-induced sepsis, acute lung injury, and cytokines release in vivo. Mechanistically, compounds 28 and 40 significantly induced phosphorylation of janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling and suppression of nuclear factor-κB (NF-κB) pathway. Furthermore, blocking α7 nAchR could effectively abolish compounds 28 and 40-mediated activation of JAK2-STAT3 signaling as well as inhibition of NF-κB activation and NO production in LPS-exposed RAW264.7 cells. Collectively, our findings have identified a new diarylheptanoid, compound 28, as an agonist of α7 nAchR-JAK2-STAT3 signaling, which can be potentially developed as a valuable candidate for the treatment of sepsis, and provide a new lead structure for the development of anti-inflammatory agents targeting α7 nAchR-JAK2-STAT3 signaling.

The glycosylation of protecting-group-free pyranoses with flavonoids to generate flavonoid O-glycosides under Mitsunobu conditions was reported. The methodology allows to prepare a wide range of natural 7-flavonoid O-glycosides and their derivatives from commercially available chemicals in good to excellent yields with exclusive 1,2-trans-stereoselectivity regardless the anomeric configuration of employed pyranoses. The highly regioselective glycosylation was also achieved among different types of hydroxyl groups on the glycosyl acceptors.

Transforming growth factor-beta (TGF-β) is a double-edged sword in cancer treatment because of its pivotal yet complex and roles played during cancer initiation/development. Current anti-cancer strategies involving TGF-β largely view TGF-β as an onco-therapeutic target that not only substantially hinders its full utilisation for cancer control, but also considerably restricts innovations in this field. Thereby, how to take advantages of therapeutically favourable properties of TGF-β for cancer management represents an interesting and less investigated problem. Here, by categorising cancer hallmarks into four critical transition events and one enabling characteristic controlling cancer initiation and progression, and delineating TGF-β complexities according to these cancer traits, we identify the suppressive role of TGF-β in tumour initiation and early-stage progression and its promotive functionalities in cancer metastasis as well as other cancer hallmarks. We also propose the feasibility and possible scenarios of combining cold atmospheric plasma (CAP) with onco-therapeutics utilising TGF-β for cancer control given the intrinsic properties of CAP against cancer hallmarks.

Background Rapid Advice Guidelines (RAG) provide decision makers with guidance to respond to public health emergencies by developing evidence-based recommendations in a short period of time with a scientific and standardized approach. However, the experience from the development process of a RAG has so far not been systematically summarized. Therefore, our working group will take the experience of the development of the RAG for children with COVID-19 as an example to systematically explore the methodology, advantages, and challenges in the development of the RAG. We shall propose suggestions and reflections for future research, in order to provide a more detailed reference for future development of RAGs. Result The development of the RAG by a group of 67 researchers from 11 countries took 50 days from the official commencement of the work (January 28, 2020) to submission (March 17, 2020). A total of 21 meetings were held with a total duration of 48 h (average 2.3 h per meeting) and an average of 16.5 participants attending. Only two of the ten recommendations were fully supported by direct evidence for COVID-19, three recommendations were supported by indirect evidence only, and the proportion of COVID-19 studies among the body of evidence in the remaining five recommendations ranged between 10 and 83%. Six of the ten recommendations used COVID-19 preprints as evidence support, and up to 50% of the studies with direct evidence on COVID-19 were preprints. Conclusions In order to respond to public health emergencies, the development of RAG also requires a clear and transparent formulation process, usually using a large amount of indirect and non-peer-reviewed evidence to support the formation of recommendations. Strict following of the WHO RAG handbook does not only enhance the transparency and clarity of the guideline, but also can speed up the guideline development process, thereby saving time and labor costs.

We note that intussusception was likely associated with severe acute respiratory syndrome coronavirus-2 infection in 2 infants in Wuhan and London. The intussusception was reduced by enemas in Wuhan; the outcome was fatal. The intussusception was not reduced by enemas in London and required surgery; the outcome was favorable.

SARS-CoV-2 Infection in Children In this report, investigators in Wuhan, China, describe the spectrum of Covid-19 illness in children under the age of 16 years. Of 1391 children assessed and tested...

Online learning techniques have been widely used in many fields where instances come one by one. However, in early stage of a data stream, online learning models cannot exhibit good classification accuracy for it cannot collect sufficient instances to learn. For example, a well-known online learning algorithm named as very fast decision tree (VFDT) needs to wait for Hoeffding bound satisfied to split, which leads to poor classification accuracy at the beginning of data stream. Thus, VFDT may not be appropriate for some real applications which demand us a fast and accurate online detection. This situation will become more serious in the scenario of data stream classification with concept drift. This paper attempts to take transfer learning algorithm to make up this shortcoming of VFDT. To achieve this goal, a new decision tree method named as VFDT-D is first proposed to cache instances in its leaf nodes to handle numerical attributes and adapt to a framework of online transfer learning (OTL), and then a measure which considers tree path, classification accuracy and classification confidence is proposed to evaluate the local similarity between source and target domain classifiers. At last, a multiple-source online transfer learning algorithm named as DMOTL is proposed to take VFDT-D as base classifier and use the proposed measure of local similarity to select the optimal source domain classifier to help transfer learning. The extensive experiments on several synthetic and real-world datasets demonstrate the advantage of the proposed algorithm.

A series of new doramectin derivatives containing carbamate, ester and sulfonate were synthesized, and their structures were characterized by 1H and 13C nuclear magnetic resonance (NMR) and high-resolution mass spectrum (HRMS). Their insecticidal activities against oriental armyworm, diamondback moth, and corn borer were evaluated and compared with the parent doramectin and commercial avermectins, metolcarb, fenpropathrin. Among all compounds, three compounds (3a, 3g and 3h) showed excellent insecticidal effect. In particular, compound 3g containing cyclopropyl carbamate against oriental armyworm, diamondback moth, and corn borer, exhibited the most promising insecticidal activity with the final mortality rate of 66.67%, 36.67%, 40.00% at the concentration of 12.5 mg/L, respectively. The LC50 values of 3g were 5.8859, 22.3214, and 22.0205 mg/L, showing 6.74, 2.23, 2.21-fold higher potency than parent doramectin (LC50 values of 39.6907, 49.7736, and 48.6129 mg/L) and 6.83, 1.93, 3.36-fold higher potency than commercial avermectins (LC50 values of 40.2489, 42.9922, and 73.9508 mg/L). Additionally, molecular docking simulations revealed that 3g displayed stronger hydrogen-bonding action in binding with the GABA receptor than parent doramectin, which were crucial for keeping high insecticidal activity. The present work demonstrated that these compounds containing alkyl carbamate group could be considered as potential candidates for the development of novel pesticides in the future.

OBJECTIVE To compare the efficacy of inhaled glucocorticoid with or without tiotropium bromide in the treatment of patients with asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS). STUDY DESIGN An experimental study. PLACE AND DURATION OF STUDY Department of Respiratory Medicine, Wuwei People's Hospital, Gansu Province, China, from October 2016 to October 2017. METHODOLOGY A total of 86 ACOS patients were randomly divided into the control group and the observation group, with 43 cases in each group. Control group was given inhaled glucocorticoid. Observation group was treated with tiotropium bromide on the basis of the control group. The asthma control test (ACT) score, chronic obstructive pulmonary disease assessment test (CAT) score, serum high-sensitivity C-reactive protein (hs-CRP) and IL-6 levels were compared. RESULTS Before treatment, there was no significant difference in ACT score, CAT score, serum hs-CRP and IL-6 levels between the two groups (p=0.808, 0.612, 0.872 and 0.921, respectively). After treatment, ACT score in observation group was higher than that in control group (p

Supercapacitors (SCs) with high gravimetric and volumetric performances are highly demanded for diverse applications, but still remain challenge to achieve for traditional porous carbon materials due to the unbalance between porous properties and high density. Herein, we report a novel oxygen-enriched crumpled graphene (OCGN) with high density prepared through a simple and facile strategy. The as-prepared OCGN possesses several advantageous features of abundant stable active oxygen-containing functional groups (17.26%), high packing density (1.28 g cm−3) and facile ion channel, resulting in high gravimetric and volumetric specific capacitance (300.5 F g−1, 384.6 F cm−3), outstanding rate performance and cyclic stability. In addition, the assembled symmetric SC exhibits a large gravimetric and volumetric energy density of 20.4 Wh kg−1 and 26.1 Wh L−1 in aqueous electrolyte, which is higher than majority of previously reported carbon-based aqueous SCs. The encouraging results demonstrate that designing oxygen-enriched carbon materials with high density may be a novel strategy to realize both high gravimetric and volumetric performance.

Here, we report the development of novel PET radiotracer ([11C]CW22) of BET proteins. In vivo imaging results in rodents and nonhuman primates (NHP) demonstrate that [11C]CW22 has excellent brain uptake, good specificity, good selectivity, suitable metabolism, appropriate kinetics and distribution in the brain. Our studies demonstrated that [11C]CW22 exhibits ideal properties as a PET imaging probe of BET proteins for further validation.

Improvements in imaging technologies have led to a greater frequency of detecting pancreatic cystic lesions...

Seven impurities were detected in doramectin bulk drug by HPLC analysis. These impurities were named as Imp-I, Imp-II, Imp-III, Imp-IV, Imp-V, Imp-VI, and Imp-VII. All impurities were isolated from doramectin bulk drug by means of preparative HPLC. Among impurities, Imp-IV and Imp-V were unknown and have not been reported previously. Based on the complete spectral analysis, including 1D (1H, 13C, H-D, DEPT 90 and 135), 2D (COSY, HSQC, HMBC, and NOESY) NMR, IR, and ESI-HRMS, the structure of Imp-IV and Imp-V were elucidated. Imp-IV was found to be a furan ring-opening product, while Imp-V lacked a methyl group at the C-14 in doramectin. Identification, isolation, structural characterization, probable formation mechanism, and insecticidal activity of impurities of doramectin were also discussed.