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.

Self-Assessed Educational Needs of Chinese Pediatric Clinicians Regarding Pediatric Palliative Care: A Cross-Sectional Investigation.

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.

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.

Ascertaining sensitive exposure biomarkers of various metal(loid)s to embryo implantation.

Close relationships exist between metal(loid)s exposure and embryo implantation failure (EIF) from animal and epidemiological studies. However, there are still inconsistent results and lacking of sensitive metal(loid) exposure biomarkers associated with EIF risk. We aimed to ascertain sensitive metal(loid) biomarkers to EIF and provide potential biological explanations. Candidate metal(loid) biomarkers were measured in the female hair (FH), female serum (FS), and follicular fluid (FF) with various exposure time periods. An analytical framework was established by integrating epidemiological association results, comprehensive literature searching, and knowledge-based adverse outcome pathway (AOP) networks. The sensitive biomarkers of metal(loid)s along with potential biological pathways to EIF were identified in this framework. Among the concerned 272 candidates, 45 metal(loid)s biomarkers across six time periods and three biomatrix were initially identified by single-metal(loid) analyses. Two biomarkers with counterfactual results according to literature summary results were excluded, and a total of five biomarkers were further determined from 43 remained candidates in mixture models. Finally, four sensitive metal(loid) biomarkers were eventually assessed by overlapping AOP networks information, including Se and Co in FH, and Fe and Zn in FS. AOP networks also identified key GO pathways and proteins involved in regulation of oxygen species biosynthetic, cell proliferation, and inflammatory response. Partial dependence results revealed Fe in FS and Co in FH at their low levels might be potential sensitive exposure levels for EIF. Our study provided a typical framework to screen the crucial metal(loid) biomarkers and ascertain that Se and Co in FH, and Fe and Zn in FS played an important role in embryo implantation.

Respiratory Viruses and Mycoplasma Pneumoniae Surveillance Among Hospitalized Children with Acute Respiratory Infections - Wuhan City, Hubei Province, China, September-November 2023.

What is already known about this topic?: Acute respiratory infections (ARIs) are a significant contributor to illness and death in children. There has been a notable rise in the occurrence of ARIs and the associated pathogens in China, which has garnered worldwide attention. What is added by this report?: This study conducted a retrospective analysis of the clinical characteristics of children with ARIs in Wuhan City from September to November 2023. The study evaluated the epidemiological patterns of common respiratory viruses and Mycoplasma pneumoniae (MP), revealing a continued prevalence of MP and a growing trend of influenza. Our findings emphasize that the circulation of respiratory viruses and MP has not returned to pre-pandemic levels, underscoring the importance of enhancing surveillance for respiratory pathogens. What are the implications for public health practice?: The epidemiology of ARIs and the pathogens involved need to be emphasized. This highlights the importance of developing policies to protect children from respiratory pathogens such as MP, influenza, and respiratory syncytial virus.

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.

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.

Molecular epidemiology of Mycoplasma pneumoniae pneumonia in children, Wuhan, 2020-2022.

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.

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.

Effect of α-methyl on the performance of photocurable 3D printing polyurethane materials.

For photosensitive polyurethane systems, reactive diluents are indispensable components whose main role is to reduce the viscosity of the polyurethane prepolymer to meet the requirements of the photocurable 3D printing technology for high fluidity of the precursor solution. Generally, the reactive diluent would be involved in the photocuring reaction, which in turn has a remarkable impact on the mechanical, reaction kinetics, and thermodynamic characteristics of the photosensitive polyurethane system. However, this feature is usually neglected in the study of photosensitive urethane acrylate (PUA) systems, so there is a considerable necessity to investigate the mechanism of active diluents in the photocured reaction of PUA systems. In this work, the effects of α-methyl groups along the chains of diluent molecules on the photoreaction kinetics, photocurable 3D printing, mechanical and mechanical properties, and thermodynamic characteristics of PUAs were investigated employing hydroxyethyl methacrylate and hydroxyethyl acrylate as active diluents, respectively. The relationship between chemical structure and kinetics of PUA systems was also elucidated by using dynamic mechanical analysis tests. The results demonstrated that the α-methyl group blocks the migration of reactive radicals, reduces the efficiency of the photoreaction, and causes an increase in the rigidity and strength of the molecular chain. This study not only revealed the effect of α-methyl on the kinetic mechanical and thermal performance of PUA systems but also paves the way for the development of a new class of photosensitive PUA materials used for the photocurable 3D printing technology.

Development and Pharmacochemical Characterization Discover a Novel Brain-Permeable HDAC11-Selective Inhibitor with Therapeutic Potential by Regulating Neuroinflammation in Mice.

Recent studies have shown that the epigenetic protein histone deacetylase 11 (HDAC11) is highly expressed in the brain and critically modulates neuroimmune functions, making it a potential therapeutic target for neurological disorders. Herein, we report the development of PB94, which is a novel HDAC11 inhibitor. PB94 exhibited potency and selectivity against HDAC11 with IC50 = 108 nM and >40-fold selectivity over other HDAC isoforms. Pharmacokinetic/pharmacodynamic evaluation indicated that PB94 possesses promising drug-like properties. Additionally, PB94 was radiolabeled with carbon-11 as [11C]PB94 for positron emission tomography (PET), which revealed significant brain uptake and metabolic properties suitable for drug development in live animals. Furthermore, we demonstrated that neuropathic pain was associated with brain upregulation of HDAC11 and that pharmacological inhibition of HDAC11 by PB94 ameliorated neuropathic pain in a mouse model. Collectively, our findings support further development of PB94 as a selective HDAC11 inhibitor for neurological indications, including pain.

Impacts of extracellular polymeric substances on the behaviors of micro/nanoplastics in the water environment.

Increasing pollution of microplastics (MPs) and nanoplastics (NPs) has caused widespread concern worldwide. Extracellular polymeric substances (EPS) are natural organic polymers mainly produced by microorganisms, the major components of which are polysaccharides and proteins. This review focuses on the interactions that occur between EPS and MPs/NPs in the water environment and evaluates the effects of these interactions on the behaviors of MPs/NPs. EPS-driven formation of eco-corona, biofilm, and "marine snow" can incorporate MPs and NPs into sinking aggregates, resulting in the export of MPs/NPs from the upper water column. EPS coating greatly enhances the adsorption of metals and organic pollutants by MPs due to the larger specific surface area and the abundance of functional groups such as carboxyl, hydroxyl and amide groups. EPS can weaken the physical properties of MPs. Through the synergistic action of different extracellular enzymes, MPs may be decomposed into oligomers and monomers that can enter microbial cells for further mineralization. This review contributes to a comprehensive understanding of the dynamics of MPs and NPs in the water environment and the associated ecological risks.

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.