A novel SERS-lateral flow assay (LFA) tray for monitoring of miR-155-5p during pyroptosis in breast cancer cells.

In the study, a novel surface-enhanced Raman scattering (SERS)-lateral flow assay (LFA) tray for the real-time detection of pyroptosis-associated miR-155-5p in breast cancer cells was established and validated. The SERS probe modified with monoclonal antibodies and functionalized HP1@5-FAM was first synthesized. When miR-155-5p was present, HP1@5-FAM on the SERS probe specifically recognized target miRNAs and hybridized with them, resulting in HP2 on the T line only capturing some SERS probes that were not bound to miR-155-5p. The T line appeared as a light orange band or there was no color change, and the corresponding Raman detection result showed a weak or insignificant Raman signal. The SERS probe showed high selectivity, satisfactory stability, and excellent reproducibility, and the limit of detection (LOD) for miR-155-5p was 7.26 aM. Finally, the proposed SERS-LFA tray was applied to detect miR-155-5p in MBA-MD-468 cells that underwent varying degrees of pyroptosis, and the detection results of SERS were consistent with those of the conventional real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay. The study demonstrated that the SERS-LFA tray was a convenient and ultrasensitive method for miR-155-5p real-time detection, which could provide more detailed information for pyroptosis and be of potential value in guiding the treatment of breast cancer.

PAHs contamination in ports: Status, sources and risks.

Polycyclic aromatic hydrocarbons (PAHs) constitute important organic contaminants that have been degrading coastal ecosystems over the years. Evaluating PAH status in port ecosystems aligns with societal goals of maintaining clean habitats and sustainability. This comprehensive review systematically analyzed 123 articles, exploring the global distribution, sources, and ecological risks linked to PAH contamination in ports, focusing on water, sediment, and biota. The mean concentrations of 16 PAHs in water, sediment, and biota across worldwide ports were 175.63 ± 178.37 ng/L, 1592.65 ± 1836.5 µg/kg, and 268.47 ± 235.84 µg/kg, respectively. In line with PAH emissions and use in Asia, Asian ports had the highest PAH concentrations for water and biota, while African ports had the highest PAH concentrations for sediment. The temporal trend in PAH accumulation in sediments globally suggests stability. However, PAH concentrations in water and biota of global ports exhibit increasing trends, signaling aggravating PAH contamination within port aquatic ecosystems. Some ports exhibited elevated PAH levels, particularly in sediments with 4.5 %, 9.5 %, and 21 % of the ports categorized as very poor, poor, and moderate quality. Some PAH isomers exceeded guidelines, including the carcinogenic Benzo(a)pyrene (BaP). Coal, biomass, and petroleum combustion were major sources for PAHs. The structure of ports significantly influences the concentrations of PAHs. PAH concentrations in sediments of semi-enclosed ports were 3.5 times higher than those in open ports, while PAH concentrations in water and biota of semi-enclosed ports were lower than those in open ports. Finally, risk analyses conducted through Monte Carlo simulation indicated moderate to high risks to aquatic species, with probabilities of 74.8 % in water and 34.4 % in sediments of ports worldwide. This review underscores the imperative to delve deeper into the accumulation of PAHs and similar pollutants in ports for effective management and environmental protection.

Adsorption of Pyrene and Arsenite by Micro/Nano Carbon Black and Iron Oxide.

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.

Degradation of Benzo[a]pyrene and 2,2',4,4'-Tebrabrominated Diphenyl Ether in Cultures Originated from an Agricultural Soil.

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.

Activated phosphoinositide 3-kinase δ syndrome caused by PIK3CD mutations: expanding the phenotype.

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.

Bacterial response to the combined pollution of benzo[a]pyrene and decabromodiphenyl ether in soil under flooding anaerobic condition.

This study investigated the interaction between the co-pollutants of Benzo[a]pyrene (BaP) and decabromodiphenyl ether (BDE-209) and the bacterial community in soil under flooding anaerobic condition. Three levels of combined pollution (at nominal concentrations of 1, 5, and 25 mg/kg, respectively, for each pollutant), their corresponding sterilized controls, and a blank control (CK) were set up. During the incubation time of 270 days, BaP attenuated more easily than BDE-209. The second-order rate constant of BaP attenuation was negatively correlated with the Ln value of initial BaP concentration. Maximal difference in bacterial community occurred between the CK soil and the highly polluted soil. Desulfomonilaceae, Parcubacteria and Rhodanobacter were probably involved in BaP and BDE-209 degradation, while Nitrosomonadaceae, Phenylobacterium and Mitochondria were significantly suppressed by BaP and BDE-209 or their degrading products. Genes narI, bcrC, fadJ, had, dmpC, narG and CfrA were involved in the degradation of BaP and BDE-209. Impacts of BaP and BDE-209 on metabolisms of carbon, nitrogen and sulfur were not significant. The results provide guidance for the management and remediation of the contaminated soil.

Prevalence of respiratory viruses among hospitalized children with lower respiratory tract infections during the COVID-19 pandemic in Wuhan, China.

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.

Design, synthesis and structure-activity relationship studies on erianin analogues as pyruvate carboxylase inhibitors in hepatocellular carcinoma cells.

A series of novel erianin analogues were designed and synthesized based on the bioisosterism principle by altering the two aromatic rings of erianin, the substituents on the rings and the linker between them. The analogues were evaluated as pyruvate carboxylase (PC) inhibitors in hepatocellular carcinoma cells. It was found that compounds 35 and 36, where fluorine replaces a hydroxyl group, exhibited higher activity than erianin (IC50 value of 17.30 nM) in liver cancer cells with IC50 values of 15.15 nM and 10.05 nM, respectively. Additionally, at a concentration of 10 nM, compounds 35 and 36 inhibited PC with inhibitory rates of 39.10% and 40.15%, respectively, exhibiting nearly identical inhibitory activity to erianin (inhibitory rate of 40.07%). Additionally, a computer simulation docking study demonstrated the basis for better interactions between the receptors and ligands. The fluorine atom of 35 can not only form hydrogen bonds with Lys-1043 (NH⋯F, 2.04 Å), but also form fluorine bonds with the carbonyl groups of Lys-1043 (3.67 Å) and Glu-1046 (3.70 Å), due to the different orientations of the halogens on the B ring warhead. Conversely, the chlorine atom of 34 can only form alkyl hydrophobic interactions with the alkane chain in Lys-1043. Fluorinated compounds 35 and 36 also show better chemical stability and higher log P (clog P = 3.89 for 35 and 36) values than that of erianin (clog P = 3.07), and may be used as candidate compounds for further drug development.

Simple and Ultrasensitive Detection of Glioma-Related ctDNAs in Mice Serum by SERS-Based Catalytic Hairpin Assembly Signal Amplification Coupled with Magnetic Aggregation.

Purpose: Circulating tumor DNA (ctDNA) is more representative and accurate than biopsy and is also conducive to dynamic monitoring, facilitating accurate diagnosis and prognosis of glioma. Therefore, the present study aimed to establish and validate a novel amplified method for the detection of IDH1 R132H and BRAF V600E, which were associated with the genetic diagnosis of glioma. Patients and Methods: A dual-signal amplification method based on magnetic aggregation and catalytic hairpin assembly (CHA) was constructed for the simultaneous detection of ctDNAs. When target ctDNAs are present, the CHA reaction is initiated and leads to the assembly of Au-Ag nanoshuttles (Au-Ag NSs) onto magnetic beads (MBs). Further enrichment of MBs under an external magnetic field facilitated the dual-signal amplification of SERS. Results: The limit of detection (LOD) for IDH1 R132H and BRAF V600E in serum was as low as 6.01 aM and 5.48 aM. The reproducibility and selectivity of the proposed SERS analysis platform was satisfactory. Finally, the platform was applied to quantify IDH1 R132H and BRAF V600E in the serum of subcutaneous-tumor­bearing nude mice, and the results obtained by SERS were consistent with those from quantitative real-time polymerase chain reaction (qRT-PCR). Conclusion: The present study showed that the dual-signal amplification method is a simple and ultrasensitive strategy for gliomas-associated ctDNAs detection, which is crucial for early diagnosis and dynamic monitoring.

Association of mental health status between self-poisoning suicide patients and their family members: a matched-pair analysis.

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 < 0.001) were protective factors for anxiety, while divorced or widowed marital status (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.

Mouse promyelocytic leukemia zinc finger protein (PLZF) regulates hepatic lipid and glucose homeostasis dependent on SIRT1.

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.

Sensitive SERS detection of oral squamous cell carcinoma-related miRNAs in saliva via a gold nanohexagon array coupled with hybridization chain reaction amplification.

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@HP1-1, Au-Ag HNPs@4-MBA@HP2-1, Au-Ag HNPs@DTNB@HP1-2, and Au-Ag HNPs@DTNB@HP2-2), and the hairpin DNA-modified AuNH array acted as the capture substrate. The HCR process could be triggered by the presence of target miRNAs, and long DNA hybridization chains on the substrate were formed by self-assembly rapidly, causing significant signal enhancement. Using the mentioned strategy, a low detection limit (LOD) of 6.51 aM for miR-31 and 6.52 aM for miR-21 in human saliva were obtained, showing the biosensor's remarkable sensitivity. The proposed biosensor also displays a significant specificity in detecting target miRNAs by introducing different interfering factors. This method has been successfully applied to detect and identify miR-21 and miR-31 in saliva from oral squamous cell carcinoma (OSCC) patients and healthy subjects. The results were consistent with those of the traditional test method in detecting target miRNAs, which confirmed the good accuracy of our method. Hence, the new assay method has great potential to be a valuable platform for detecting miRNAs in the early diagnosis of OSCC.

Roles of TGF-ß in cancer hallmarks and emerging onco-therapeutic design.

Transforming growth factor-beta (TGF-ß) 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-ß largely view TGF-ß 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-ß 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-ß complexities according to these cancer traits, we identify the suppressive role of TGF-ß 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-ß for cancer control given the intrinsic properties of CAP against cancer hallmarks.

Discovery of a Novel Small-Molecule Inhibitor Disrupting TRBP-Dicer Interaction against Hepatocellular Carcinoma via the Modulation of microRNA Biogenesis.

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 in vitro and in vivo by modulating expression profiles of miRNAome and proteome in HCC cells. Mechanistically, CIB-3b physically binds to transactivation response (TAR) RNA-binding protein 2 (TRBP) and disrupts the TRBP-Dicer interaction, thereby altering the activity of Dicer and mature miRNA production. Structure-activity relationship study via the synthesis of 45 CIB-3b derivatives showed that some compounds exhibited a similar inhibitory effect on miRNA biogenesis to CIB-3b. These results support TRBP as a potential therapeutic target in HCC and warrant further development of CIB-3b along with its analogues as a novel therapeutic strategy for the treatment of HCC.

Discovery of diarylheptanoids that activate α7 nAchR-JAK2-STAT3 signaling in macrophages with anti-inflammatory activity in vitro and in vivo.

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-1ß (IL-1ß) 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.

Magnesium dicarboxylates promote the prenylation of phenolics that is extended to the total synthesis of icaritin.

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 ortho- vs. para-prenylation (3'vs.3'') for those para-unoccupied substrates was also solvent dependant. DMF produced mainly ortho-products but with poor conversions. On the other hand, MeCN generated mainly para-products, along with minor ortho-products. Mechanistic study of the prenylation provided evidence for the nucleophilic addition/substitution of the phenolic substrate to the alkyl halide in the presence of the magnesium dicarboxylates. The proto application of this method in the total synthesis of icaritin through the prenylation of 2,4,6-trihydroxyacetophenone, followed by the reaction with benzaldehyde to afford the flavonol, was successful, with a total yield of 33%.

Pathogenic characteristics and treatment in 43 cases of acute colchicine poisoning.

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.

Human Adenovirus Type 7 Infections in Hubei, China During 2018-2019: Epidemic Features and Genetic Characterization of the Detected Viruses.

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.

Co-infections of SARS-CoV-2 with multiple common respiratory pathogens in infected children: A retrospective study.

ABSTRACT: Since the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, considerable attention has been paid on its epidemiology and clinical characteristics in children patients. However, it is also crucial for clinicians to summarize and investigate the co-infection of SARS-CoV-2 in children.We retrospectively reviewed the clinical manifestations, laboratory findings, and imaging characteristics of COVID-19 patients in co-infection group (CI, n = 27) and single infection group (SI, n = 54). Samples were tested for multiple pathogens.A high incidence (27/81, 33%) of co-infection in children with COVID-19 was revealed. The most frequent co-infected pathogen was mycoplasma pneumoniae (MP, 20/81, 25%), followed by virus (6/81, 7%), and bacteria (4/81, 5%). No significant difference in clinical characteristics, laboratory examinations, or hospital stay was observed between the patients with co-infections and those with monomicrobial, only lower in white blood cell counts (CI: 5.54 ±â€Š0.36 vs SI: 7.38 ±â€Š0.37, P = .002), neutrophil counts (CI: 2.20 ±â€Š0.20 vs SI: 2.92 ±â€Š0.23, P = .024) and lymphocyte counts (CI: 2.72 ±â€Š0.024 vs SI: 3.87 ±â€Š0.28, P = .006). Compared with the patients with monomicrobial, chest imaging of those with co-infections showed consolidation in more cases (CI: 29.6% vs SI: 11.1%, P = .038) and duration of positive in nucleic acid was shorter (CI: 6.69 ±â€Š0.82 vs SI: 9.69 ±â€Š0.74, P = .015).Co-infection was relatively common in children with COVID-19, almost 1/3 had co-infection, most commonly caused by MP. Co-infection did not cause a significant exacerbation in clinical manifestations.

Clinical analysis and pluripotent stem cells-based model reveal possible impacts of ACE2 and lung progenitor cells on infants vulnerable to COVID-19.

Introduction: An increasing number of children with severe coronavirus disease 2019 (COVID-19) is being reported, yet the spectrum of disease severity and expression patterns of angiotensin-converting enzyme 2 (ACE2) in children at different developmental stages are largely unknow. Methods: We analysed clinical features in a cohort of 173 children with COVID-19 (0-15 yrs.-old) between January 22, 2020 and March 15, 2020. We systematically examined the expression and distribution of ACE2 in different developmental stages of children by using a combination of children's lung biopsies, pluripotent stem cell-derived lung cells, RNA-sequencing profiles, and ex vivo SARS-CoV-2 pseudoviral infections. Results: It revealed that infants (< 1yrs.-old), with a weaker potency of immune response, are more vulnerable to develop pneumonia whereas older children (> 1 yrs.-old) are more resistant to lung injury. The expression levels of ACE2 however do not vary by age in children's lung. ACE2 is notably expressed not only in Alveolar Type II (AT II) cells, but also in SOX9 positive lung progenitor cells detected in both pluripotent stem cell derivatives and infants' lungs. The ACE2+SOX9+ cells are readily infected by SARS-CoV-2 pseudovirus and the numbers of the double positive cells are significantly decreased in older children. Conclusions: Infants (< 1 yrs.-old) with SARS-CoV-2 infection are more vulnerable to lung injuries. ACE2 expression in multiple types of lung cells including SOX9 positive progenitor cells, in cooperation with an unestablished immune system, could be risk factors contributing to vulnerability of infants with COVID-19. There is a need to continue monitoring lung development in young children who have recovered from SARS-CoV-2 infection.