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Abstract Immunodeficiency 11B with atopic dermatitis (IMD11B, OMIM:617638) is rare primary immunodeficiency disease caused by germline dominant negative (DN) mutations in the CARD11 gene. Affected patients present with immune dysfunction, recurrent infections and atopic dermatitis. In this study, we sought to identify and characterize the genetic variant in one patient with periodic fever, recurrent infections, and eczema. Trio whole-exome sequencing (WES) was employed in this patient and her parents, and Sanger sequencing validated the potential pathogenic variant. In vitro functional study was performed to evaluate the pathogenicity of genetic variant identified. A very rare missense mutation (c.2324C > T, p.S775L) in CARD11 gene (NM_032415) was identified by WES in the patient but not her parents. Luciferase reporter assays and co-immunoprecipitation demonstrated mutation exerts a dominant-interfering effect on wild-type CARD11, inhibiting the activity of NF-κB. RNA sequencing analysis also confirmed that mutant CARD11 inhibited down-stream transcriptional activity of NF-κB. A review of literature doesn’t found significant genotype–phenotype correlation. We identified a vary rare DN CARD11 mutation, expanding the genetic and phenotypic spectrum of CARD11.

AimsTo investigate the epidemiological and clinical characteristics of children with Mycoplasma pneumoniae pneumonia (MPP) in Hubei, China.MethodsWe retrospectively analyzed inpatients with MPP from 20 hospitals in Hubei, China from January 2021 to December 2022. The co-detected pathogens of Mycoplasma pneumoniae (M. pneumoniae) were investigated using targeted next-generation sequencing (tNGS), and 23S rRNA gene mutations were analyzed to assess the macrolide resistance.ResultsM. pneumoniae infected 20.7% of patients with CAP, with cough (96.59%) and fever (80.28%) being the most prevalent symptoms. The infection rates in children younger than 1, 1–2, 3–6, 7–12, and older than 12 years were 6.17%, 19.98%, 26.97%, 43.93%, and 2.95%, respectively. Among 1,349 patients undergoing tNGS, the overall co-detection rate was 59.45%, with Streptococcus pneumoniae (29.30%), Haemophilus influenzae (23.57%), and Human rhinovirus (17.21%) being the most commonly co-detected pathogens. In 635 patients undergoing the 23S rRNA gene mutation test, 86.30% exhibited positive mutations (A2063G, 98.00%; A2064G, 1.50%; A2067G, 0.50%). Despite a significant age difference (P = 0.037) between macrolide-resistant M. pneumoniae and macrolide-sensitive M. pneumoniae groups, there were no significant differences in symptoms, lab data, or disease severity.ConclusionsIn Hubei Province, the prevalence of exhibited consistent changes during the COVID-19 pandemic. MPP was prevalent year-round, particularly in summer and autumn, with school-age children being more susceptible. Co-detections of viruses and bacteria were frequent in MPP cases, and macrolide resistance exceeded 85%. Ongoing surveillance of M. pneumoniae in children is crucial for understanding the healthcare impact of MPP.

Objectives: We aimed to investigate the continuous changes in respiratory virus epidemics in hospitalized children with lower respiratory tract infections (LRTIs) persisting from January 2019 to December 2022 in Wuhan, China. Methods: We retrospectively enrolled children with LRTIs admitted to the Wuhan Children's Hospital. Specimens were nasopharyngeal aspirates which had been collected and detected the following microorganisms with direct immunofluorescence: influenza virus types A and B, respiratory syncytial virus, parainfluenza virus types 1-3, and adenovirus. We also analyzed demographic data and laboratory test results. Results: A total of 22,660 patients were enrolled. The total virus detection rate in 2019, 2021, and 2022 significantly declined gradually (36.96% vs 29.47% vs 22.62%, P value < 0.001). All the detected viruses did not follow previously observed seasonal patterns during the COVID-19 pandemic. Children hospitalized for LRTIs were older during the COVID-19 pandemic in contrast to the pre-period, particularly notable in cases attributed to respiratory syncytial virus and parainfluenza virus type 3 infections. Conclusions: This work adds to our knowledge of the epidemiology characteristics of respiratory viruses spanning the COVID-19 pandemic among children with LRTIs. The circulation of respiratory viruses changed consistently, and active LRTI surveillance in children remains critical for defining the healthcare burden of respiratory viruses.

Path planning refers to finding the optimal path from the starting point to the endpoint in a given environment, avoiding obstacles. To solve the problem of slow convergence speed in particle swarm optimization in path planning, this paper proposes a robot path planning based on generative learning Particle Swarm Optimization (LPSO). This algorithm constructs a generative double-adversarial network. In the first stage, the generator was used to analyze and process the initial map to obtain a foreground area with feasible paths. This area is used for heuristic search of particle swarms, reducing unnecessary exploration areas for particles throughout the state space, and quickly achieving path planning goals. In the second stage, the foreground region obtained in the first stage is used as the global optimal particle path for particle swarm optimization, and the particles are guided to move in the direction of high-density pheromones. Finally, the obstacle avoidance strategy enables the robot to avoid moving obstacles safely. In addition to being adapted to simple raster maps, this method also performs well in actual environment maps, showing superior generalization ability. To verify the effectiveness of the proposed algorithm, a series of simulation experiments are compared with the traditional PSO, ant colony algorithm (ACO), and improved algorithms, and the results show that under the same map environment, the LPSO algorithm has a faster convergence speed and shorter planning time and path length.

Abstract Background Germline heterozygous gain-of-function (GOF) mutations in the PIK3CD gene lead to a rare primary immunodeficiency disease known as activated phosphoinositide 3-kinase (PI3K) δ syndrome type 1(APDS1). Affected patients present a spectrum of clinical manifestations, particularly recurrent respiratory infections and lymphoproliferation, increased levels of serum immunoglobulin (Ig) M, Epstein-Barr virus (EBV) and cytomegalovirus (CMV) viremia. Due to highly heterogeneous phenotypes of APDS1, it is very likely that suspected cases may be misdiagnosed. Methods Herein we reported three patients with different clinical presentations but harboring pathogenic variants in PIK3CD gene detected by trio whole-exome sequencing (trio-WES) and confirmed by subsequent Sanger sequencing. Results Two heterozygous mutations (c.3061G > A, p.E1021K and c.1574 A > G, p.E525G) in PIK3CD (NM_005026.3) were identified by whole exome sequencing (WES) in the three patients. One of two patients with the mutation (c.3061G > A) presented with abdominal pain and diarrhea as the first symptoms, which was due to intussusception caused by multiple polyps of colon. The patient with mutation (c.1574 A > G) had an anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)-like clinical manifestations, including multisystemic inflammation, acute nephritic syndrome, and positive perinuclear ANCA (p-ANCA), thus the diagnosis of ANCA-AAV was considered. Conclusions Our study expands the spectrums of clinical phenotype and genotype of APDS, and demonstrates that WES has a high molecular diagnostic yield for patients with immunodeficiency related symptoms, such as respiratory infections, multiple ecchymosis, ANCA-associated vasculitis, multiple ileocecal polyps, hepatosplenomegaly, and lymphoid hyperplasia. Trial registration Retrospectively registered.

Background Mycoplasma pneumoniae (M. pneumoniae) is an important pathogen of community-acquired pneumonia in children. The factors contributing to the severity of illness caused by M. pneumoniae infection are still under investigation. We aimed to evaluate the sensitivity of common M. pneumoniae detection methods, as well as to analyze the clinical manifestations, genotypes, macrolide resistance, respiratory microenvironment, and their relationship with the severity of illness in children with M. pneumoniae pneumonia in Wuhan. Results Among 1,259 clinical samples, 461 samples were positive for M. pneumoniae via quantitative polymerase chain reaction (qPCR). Furthermore, we found that while serological testing is not highly sensitive in detecting M. pneumoniae infection, but it may serve as an indicator for predicting severe cases. We successfully identified the adhesin P1 (P1) genotypes of 127 samples based on metagenomic and Sanger sequencing, with P1-type 1 (113/127, 88.98%) being the dominant genotype. No significant difference in pathogenicity was observed among different genotypes. The macrolide resistance rate of M. pneumoniae isolates 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. Conclusions During the period of this study, the main circulating M. pneumoniae was P1-type 1, with a resistance rate of 96%. Key findings include the efficacy of qPCR in detecting M. pneumoniae, the potential of IgM titers exceeding 1:160 as indicators for illness severity, and the lack of a direct correlation between disease severity and genotypic characteristics or respiratory microenvironment. 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.

ABSTRACTThe aim of this study was to isolate and purify flavonoids from Jujube (Zizipus jujuba Mill.) fruit and further evaluate antibacterial activities. Semi-preparative high-performance liquid chromatography (HPLC) was used to isolate and purify the flavonoids, while nuclear magnetic resonance spectroscopy (NMR) was employed for structural identification. Five flavonoids, including epicatechin, quercetin, rutin, isoquercitrin, and hyperin were identified. Antibacterial activity assays showed quercetin had the greatest inhibitory effect on Escherichia coli, Shigella, and Pseudomonas aeruginosa, and the minimum inhibitory concentration (MIC) against Escherichia coli or Pseudomonas aeruginosa was 250 μg/mL and against Shigella was 125 μg/mL. Rutin had the greatest inhibitory effect on Staphylococcus aureus, the MIC of which was 62.5 μg/mL. Hyperin had the greatest inhibitory effect on Bacillus subtilis, the MIC of which against Bacillus subtilis was 250 μg/mL, whereas that against Staphylococcus aureus was 62.5 μg/mL. We found that the antibacterial effects of the flavonoids were strong at a pH less than 6 and that they dropped sharply with increasing pH. Furthermore, the five metal ions Na+, Ca2+, K+, Fe2+, and Mg2+ generally increased the antibacterial activity of quercetin against Escherichia coli, Shigella, and Pseudomonas aeruginosa, and that of rutin against Staphylococcus aureus. For hyperin, Ca2+ and K+ had the strongest antibacterial effects. The present study suggests that the flavonoids extracted from Jujube (Zizipus jujuba Mill.) fruit were considered a promising candidate for natural and healthy antibacterial agents for the pharmaceutical and food industries.

Abstract 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

Background: An important first step in enhancing professional palliative care training is to investigate the educational needs of pediatric clinicians in this field. The aims of this research were to analyze the extent of end-of-life care experience of Chinese pediatric clinicians and identify the differing educational needs of physicians and nurses as well as associated impact factors. Methods: A cross-sectional descriptive survey via a structural questionnaire was used in this research. Results: In total, 187 clinicians, comprising 52 physicians and 135 nurses, participated in this study. The topics “pain management”, “symptom management”, and “discussing the prognosis with family members” were the most expressed educational needs among both physicians and nurses. Compared to nurses, physicians placed greater emphasis on the importance of “communication” and “pain and symptom management” (p < 0.05). Clinicians with more extensive end-of-life care experience more strongly felt the importance of learning about pain management and communication regarding end-of-life care (p < 0.05). Conclusions: Research showed that the education currently provided to pediatric clinicians does not meet their distinctive needs. Future palliative care education must be a continuing multi-level, interdisciplinary program and different education should be provided to physicians and nurses based on their respective needs.

Polycyclic aromatic hydrocarbons (PAHs) and arsenic (As) are common pollutants co-existing in the environment, causing potential hazards to the ecosystem and human health. How their behaviors are affected by micro/nano particles in the environment are still not very clear. Through a series of static adsorption experiments, this study investigated the adsorption of pyrene and arsenite (As (III)) using micro/nano carbon black and iron oxide under different conditions. The objectives were to determine the kinetics and isotherms of the adsorption of pyrene and As (III) using micro/nano carbon black and iron oxide and evaluate the impact of co-existing conditions on the adsorption. The microstructure of micro/nano carbon black (C 94.03%) is spherical-like, with a diameter of 100–200 nm. The micro/nano iron oxide (hematite) has irregular rod-shaped structures, mostly about 1 µm long and 100–200 nm wide. The results show that the micro/nano black carbon easily adsorbed the pyrene, with a pseudo-second-order rate constant of 0.016 mg/(g·h) and an adsorption capacity of 283.23 μg/g at 24 h. The micro/nano iron oxide easily adsorbed As (III), with a pseudo-second-order rate constant of 0.814 mg/(g·h) and an adsorption capacity of 3.45 mg/g at 24 h. The mechanisms of adsorption were mainly chemical reactions. Micro/nano carbon black hardly adsorbed As (III), but its adsorption capability for pyrene was reduced by the presence of As (III), and this effect increased with an increase in the As (III) concentration. The adsorbed pyrene on the micro/nano black carbon could hardly be desorbed. On the other hand, the micro/nano iron oxide could hardly adsorb the pyrene, but its adsorption capability for As (III) was increased by the presence of pyrene, and this effect increased with an increase in the pyrene concentration. The results of this study provide guidance for the risk management and remediation of the environment when there is combined pollution of PAHs and As.

Benzo[a]pyrene (BaP) and 2,2′,4,4′-tetrabrominated diphenyl ether (BDE-47) are common contaminants in the environment, posing a threat to the ecosystems and human health. Currently, information on the microbial metabolism of BaP and BDE-47 as well as the correlated bacteria is still limited. This research aimed to study the degradation of BaP and BDE-47 by enriched cultures originated from an agricultural soil in Tianjin (North China) and characterize the bacteria involved in the degradation. Two sets of experiments were set up with BaP and BDE-47 (2 mg/L) as the sole carbon source, respectively. The degradation of BaP and BDE-47 occurred at rate constants of 0.030 /d and 0.026 /d, respectively. For BaP, the degradation products included benzo[a]pyrene-9,10-dihydrodiol or its isomers, ben-zo(a)pyrene-7,8-dihydrodiol-9,10-epoxide, and cis-4 (8-hydroxypyrenyl-7)-2-oxo-3-butenoic acid. For BDE-47, the degradation products included 2,2′,4-tribrominated diphenyl ether (BDE-17), 2,4-dibrominated diphenyl ether (BDE-7), and hydroxylated dibromodiphenyl ether. The bacterial community structures in the original soil, the BaP culture, and the BDE-47 culture were quite different. The richness and diversity of bacteria in the two cultures were much lower than that in the original soil, and the BaP culture had higher richness and diversity than the BDE-47 culture. In the BaP culture, multiple species such as Niabella (23.4%), Burkholderia-Caballeronia-Paraburkholderia (13.7%), Cupriavidus (8.3%), and Allorhizobi-um-Neorhizobium-Pararhizobium-Rhizobium (8.0%) were dominant. In the BDE-47 culture, an unassigned species in the Rhizobiaceae was dominant (82.3%). The results from this study provide a scientific basis for the risk assessment and bioremediation of BaP and/or BDE-47 in a contaminated environment.

Abstract 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.

Previous studies suggest that exposure to thiamethoxam (TMX) may cause adverse effects to human. However, the distribution of TMX in various organs of human body and the associated risk are little-known. This study aimed to explore the distribution of TMX in human organs by extrapolation from a toxicokinetic experiment in rats and to assess the associated risk based on literature data. The rat exposure experiment was performed using 6-week female SD rats. Five groups of rats were oral-exposed to 1 mg/kg TMX (water as solvent) and executed at 1 h, 2 h, 4 h, 8 h and 24 h after treatment, respectively. The concentrations of TMX and its metabolites in rat liver, kidney, blood, brain, muscle, uterus and urine were measured in different time points using LC-MS. Data on concentrations of TMX in food, human urine and blood as well as human cell-based in vitro toxicity of TMX were collected from the literature. After oral exposure, TMX and its metabolite clothianidin (CLO) were detected in all organs of the rats. The steady-state tissue-plasma partition coefficients of TMX for liver, kidney, brain, uterus and muscle were 0.96, 1.53, 0.47, 0.60 and 1.10, respectively. Based on literature analysis, the concentration of TMX in human urine and blood for general population were 0.06–0.5 ng/mL and 0.04–0.6 ng/mL, respectively. For some people, the concentration of TMX in human urine reached 222 ng/mL. By extraplation from rat experiment, the estimated concentrations of TMX in human liver, kidney, brain, uterus and muscle for general population were 0.038–0.58, 0.061–0.92, 0.019–0.28, 0.024–0.36 and 0.044–0.66 ng/g, respectively, well below the relevant concentrations for cytotoxic endpoints (HQs ≤ 0.012); however, for some people they could be up to 253.44, 403.92, 124.08, 158.40 and 290.40 ng/g, respectively, with very high developmental toxicity (HQ = 5.4). Therefore, the risk for highly exposed people should not be neglected.

Previous studies have demonstrated that promyelocytic leukemia zinc finger protein (PLZF) promotes the expression of gluconeogenic genes and hepatic glucose output, which leads to hyperglycemia. However, the role played by PLZF in regulating lipid metabolism is not known. In this study, we aimed to examine the function of PLZF in regulating hepatic lipid and glucose homeostasis and the underlying mechanisms. The expression of PLZF was determined in different mouse models with regard to non-alcoholic fatty liver disease (NAFLD). In the next step, adenoviruses that express PLZF (Ad-PLZF) or PLZF-specific shRNA (Ad-shPLZF) were utilized to alter PLZF expression in mouse livers and in primary hepatocytes. For the phenotype of the fatty liver, histologic and biochemical analyses of hepatic triglyceride (TG), serum TG and cholesterol levels were carried out. The underlying molecular mechanism for the regulation of lipid metabolism by PLZF was further explored using luciferase reporter gene assay and ChIP analysis. The results demonstrated that PLZF expression was upregulated in livers derived from ob/ob, db/db and diet-induced obesity (DIO) mice. Liver PLZF-overexpressing C57BL/6J mice showed fatty liver phenotype, liver inflammation, impaired glucose tolerance and insulin sensitivity. On the other hand, hepatic PLZF knockdown in db/db and DIO mice alleviated hepatic steatosis. Of note, we found that PLZF activates SREBP-1c gene transcription through binding directly to the promoter fragment of this gene, which would induce a repressor-to-activator conversion depending on its interaction with SIRT1 in the role played by PLZF in the transcription process through deacetylation. Thus, PLZF is identified as an essential regulator of hepatic lipid and glucose metabolism, where the modulation of its liver expression could open up a therapeutic path for treating NAFLD.

Background: Since the outbreak of Coronavirus Disease 2019 (COVID-19) in Wuhan, considerable attention has been paid to its epidemiology and clinical characteristics in children. However, it is also crucial for clinicians to differentiate COVID-19 from other respiratory infectious diseases, such as influenza viruses. Methods: This was a retrospective study. Two groups of COVID-19 patients (n = 57) and influenza A patients (n = 59) were enrolled. We analyzed and compared their clinical manifestations, imaging characteristics and treatments. Results: The proportions of cough (70.2%), fever (54.4%) and gastrointestinal symptoms (14.1%) in COVID-19 patients were lower than those of influenza A patients (98.3%, P

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.

Human adenoviruses (HAdVs) type 7 can cause severe respiratory disease. During the period between December 2018 and August 2019, HAdV-7 infection was identified in 129 patients in Wuhan Children’s Hospital, Hubei Province, China. Samples were collected from hospitalized children and metagenomic sequencing was applied to detect the HAdV infections. Hemophagocytic lymphohistiocystosis (HLH) related to HAdV infections was observed in some patients clinically and patients were divided into two groups based on this to test the differences among clinical indicators. Genome variation, in silico restriction endonuclease analysis (REA), and phylogenetic analyses were carried out to show the genome characterization of HAdV-7 in this study. It was found that many indicators, such as all blood routine indicators, in patients of the HLH group showed significant levels. In this study, REA revealed that HAdV-7 might belong to genome 7d and genome variation analysis displayed the stable genome of HAdV. HAdV-7 is an ongoing threat to the public, and global surveillance should be established.

Bromodomain and extra-terminal domain (BET) family proteins have become a hot research area because of their close relationship with a variety of human diseases. The non-invasive imaging technique, such as positron emission tomography (PET), provides a powerful tool to visualize and quantify the BET family proteins that accelerating the investigation of this domain. Herein, we describe the development of a promising PET probe, [11C]1, specifically targeting BET family proteins based on the potent BET inhibitor CF53. [11C]1 was successfully radio-synthesized with good yield and high purity after the optimization of radiolabeling conditions. The in vivo bio-activities evaluation of [11C]1 was performed using PET imaging in rodents. The results demonstrated that [11C]1 has favorable uptake in peripheral organs and moderate uptake in the brain. Further blocking studies indicated the high binding specificity and selectivity for BET proteins of this probe. Our findings suggest that [11C]1 is a promising BET PET probe for BET proteins as well as epigenetic imaging.

Background: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is ongoing globally. Limited data are available for children with SARS-CoV-2 infection.Methods: A retrospective case study was conducted in one designated hospital for children with SARS-CoV-2 infection in Wuhan.Results: Out of the 74 children with laboratory-confirmed SARS-CoV-2 infection, the median age was 5.8 years, with no notable variation based on gender. All of the children had had direct exposure to at least one family member with confirmed SARS-CoV-2 infection. The most common symptoms were cough in 41 (55.4%) and fever in 38 (51.4%). Typical CT patterns of viral pneumonia were exhibited in 40 (54.1%) children, including ground-glass opacity and interstitial abnormalities. However, 17 (23.0%) children were classified as asymptomatic carriers, with neither symptoms nor radiological findings. Also, 68 (91.9%) children recovered fully and showed negative results on RT-PCR assay by nasopharyngeal swabs during our observation period. In contrast to the negative result for nasopharyngeal swab, 34% of the anal swabs showed a continued positive result. The mean hospitalization days of the children discharged after full recovery was 10.0 days.Conclusion: Within family clusters that had SARS-CoV-2 infection, children had mild or even asymptomatic illness. Although CT is highly sensitive, it should be avoided in follow-up of the disease in consideration of the radiological hazards and limited clinical benefits for mild illness in children. Furthermore, it is advocated that both nasopharyngeal and anal swabs should be confirmed negative for viral load prior to declaring full recovery so as to avoid oral-fecal transmission. Asymptomatic children with family clusters are potentially a little-known source of COVID-19. This therefore warrants an urgent reassessment of the transmission dynamics of the current outbreak.

The orexin receptor (OX) is critically involved in motivation and sleep−wake regulation and holds promising therapeutic potential in various mood disorders. To further investigate the role of orexin receptors (OXRs) in the living human brain and to evaluate the treatment potential of orexin-targeting therapeutics, we herein report a novel PET probe ([11C]CW24) for OXRs in the brain. CW24 has moderate binding affinity for OXRs (IC50 = 0.253 μM and 1.406 μM for OX1R and OX2R, respectively) and shows good selectivity to OXRs over 40 other central nervous system (CNS) targets. [11C]CW24 has high brain uptake in rodents and nonhuman primates, suitable metabolic stability, and appropriate distribution and pharmacokinetics for brain positron emission tomography (PET) imaging. [11C]CW24 warrants further evaluation as a PET imaging probe of OXRs in the brain.

Sediments were sampled from different surface water bodies in Tianjin coastal area, China, and persistent organic pollutants (POPs) including polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs) were measured using GC/MS or GC/ECD. The purposes were to investigate the concentration levels of the POPs and to assess their ecological risks. The results showed that all the 16 priority PAHs were detected from the 10 sediments sampled with the total concentrations of the 16 PAHs ranging from 274.06 μg/kg to 2656.65 μg/kg, while the concentrations of the halogenated POPs were generally low except in the Dagu waste discharging river where the total concentrations of 24 OCPs, 35 PCBs, and 14 PBDEs were 3103.36 μg/kg, 87.31 μg/kg, and 13.88 μg/kg, respectively. In the studied sediments, PAHs exhibited risks to benthonic organisms; particularly the concentrations of naphthalene and/or acenaphthene exceeded their probable effect concentrations in several locations. In comparison, only in the Dagu waste discharging river, OCPs exhibited risks with the concentrations of heptachlor epoxide and lindane exceeding their probable effect concentrations. PCBs and PBDEs posed rare risks in the studied area.

This article explores the use of hemoperfusion and continuous veno-venous hemodiafiltration as potential treatments for chlorfenapyr poisoning, a toxic insecticide that can be fatal. The article presents a case study of a 15-year-old patient who ingested chlorfenapyr and was treated with these methods. While the treatments were able to reduce the concentration of chlorfenapyr in the patient's blood, the patient ultimately died due to complications from the poisoning. The article emphasizes the need for further research on the toxicology and treatment of chlorfenapyr poisoning, and highlights the severity of this type of poisoning. [Extracted from the article]

Abstract Menaquinone (MK) in bacterial membrane is an attractive target for the development of novel therapeutic agents. Mining the untapped chemical diversity encoded by Gram-negative bacteria presents an opportunity to identify additional MK-binding antibiotics (MBAs). By MK-binding motif searching of bioinformatically predicted linear non-ribosomal peptides from 14,298 sequenced genomes of 45 underexplored Gram-negative bacterial genera, here we identify a novel MBA structural family, including silvmeb and pseudomeb, using structure prediction-guided chemical synthesis. Both MBAs show rapid bacteriolysis by MK-dependent membrane depolarization to achieve their potent activities against a panel of Gram-positive pathogens. Furthermore, both MBAs are proven to be effective against methicillin-resistant Staphylococcus aureus in a murine peritonitis-sepsis model. Our findings suggest that MBAs are a kind of structurally diverse and still underexplored antibacterial lipodepsipeptide class. The interrogation of underexplored bacterial taxa using synthetic bioinformatic natural product methods is an appealing strategy for discovering novel biomedically relevant agents to confront the crisis of antimicrobial resistance.