Characterization of a Salmonella enterica serovar Typhimurium lineage with rough colony morphology and multidrug resistance.

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a major cause of salmonellosis, and the emergence of multidrug-resistant pathovariants has become a growing concern. Here, we investigate a distinct rough colony variant exhibiting a strong biofilm-forming ability isolated in China. Whole-genome sequencing on 2,212 Chinese isolates and 1,739 publicly available genomes reveals the population structure and evolutionary history of the rough colony variants. Characterized by macro, red, dry, and rough (mrdar) colonies, these variants demonstrate enhanced biofilm formation at 28 °C and 37 °C compared to typical rdar colonies. The mrdar variants exhibit extensive multidrug resistance, with significantly higher resistance to at least five classes of antimicrobial agents compared to non-mrdar variants. This resistance is primarily conferred by an IncHI2 plasmid harboring 19 antimicrobial resistance genes. Phylogenomic analysis divides the global collections into six lineages. The majority of mrdar variants belong to sublineage L6.5, which originated from Chinese smooth colony strains and possibly emerged circa 1977. Among the mrdar variants, upregulation of the csgDEFG operons is observed, probably due to a distinct point mutation (-44G > T) in the csgD gene promoter. Pangenome and genome-wide association analyses identify 87 specific accessory genes and 72 distinct single nucleotide polymorphisms associated with the mrdar morphotype.

Expanding the Potential of Neoantigen Vaccines: Harnessing Bacille Calmette-Guérin Cell-Wall-Based Nanoscale Adjuvants for Enhanced Cancer Immunotherapy.

Personalized antitumor immunotherapy utilizing neoantigen vaccines holds great promise. However, the limited immunogenicity of existing recognized neoantigens and the inadequate stimulation of antitumor immune responses by conventional adjuvants pose significant challenges. To address these limitations, we developed a nanovaccine that combines a BCG bacterial cell wall skeleton (BCG-CWS) based nanoscale adjuvant (BCNA) with peptide neoantigens (M27 and M30). This integrated approach provides an efficient translational strategy for cancer immunotherapy. The BCNA nanovaccine, formulated with PLGA as an emulsifier, exhibits excellent biocompatibility and superior antigen presentation compared with conventional BCG-CWS adjuvants. Subcutaneous immunization with the BCNA-based nanovaccine effectively targets lymph nodes, eliciting robust innate and tumor-specific immune responses. Importantly, our findings demonstrate that BCNAs significantly enhance neoantigen immunogenicity while minimizing acute systemic toxicity. Furthermore, when combined with a mouse PD-L1 antibody, our strategy achieves complete tumor elimination in 60% of cases and prevents 25% of tumor growth in a melanoma mouse model. In conclusion, our BCNA-based nanovaccine represents a promising avenue for advancing personalized therapeutic neoantigen vaccines and holds significant implications for enhancing personalized immunotherapy and improving patient outcomes in the field of cancer treatment.

Greenspace and human microbiota: A systematic review.

BACKGROUND: Potential effect of greenspace exposure on human microbiota have been explored by a number of observational and interventional studies, but the results remained mixed. We comprehensively synthesized these studies by performing a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. METHODS: Comprehensive literature searches in three international databases (PubMed, Embase, and Web of Science) and three Chinese databases (China National Knowledge Infrastructure, Wanfang, and China Biology Medicine disc) were conducted from inception to November 1, 2023. Observational and interventional studies that evaluated associations between greenspace exposure and human microbiota at different anatomical sites were included. Studies were assessed using the National Toxicology Program's office of Health Assessment and Translation risk of bias tool and certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation framework. Two authors independently performed study selection, data extraction, and risk of bias assessment, and evidence grading. Study results were synthesized descriptively. RESULTS: Twenty studies, including 11 observational studies and 9 interventional studies, were finally included into the systematic review. The microbiota of the included studies was from gut (n = 13), skin (n = 10), oral cavity (n = 5), nasal cavity (n = 5) and eyes (n = 1). The majority of studies reported the associations of greenspace exposure with increased diversity (e.g., richness and Shannon index) and/or altered overall composition of human gut (n = 12) and skin microbiota (n = 8), with increases in the relative abundance of probiotics (e.g., Ruminococcaceae) and decreases in the relative abundance of pathogens (e.g., Streptococcus and Escherichia/Shigella). Due to limited number of studies, evidence concerning greenspace and oral, nasal, and ocular microbiota were still inconclusive. CONCLUSION: The current evidence suggests that greenspace exposure may diversify gut and skin microbiota and alter their composition to healthier profiles. These findings would be helpful in uncovering the potential mechanisms underlying greenspace and human health and in promoting a healthier profile of human microbiota.

Study on the role of CCM3 gene and lead exposure induced neurotoxicity through neurovascular units.

This study aimed to determine the toxic effects of vascular CCM3 gene deficiency and lead (Pb) exposure on the nervous system. Lentiviral transfection was performed to generate a stable strain of brain microvascular endothelial cells with low CCM3 expression. MTT assay assessed the survival rate of cells exposed to Pb, determining the dose and duration of Pb exposure in vitro. Proteomic analysis was performed on the differentially expressed proteins in bEnd3 and HT22 cells and flow cytometry was used to detect cell apoptosis. Finally, urine samples from pregnant and postpartum women were subjected to ICP-MS to detect Pb levels and HPLC to detect neurotransmitter metabolites. Based on the proteomic analysis of bEnd3 (CCM3-/-) cells co-cultured with HT22 cells, it was determined that HT22 cells and CCM3 genes interfered with bEnd3 cell differential proteins,2 including apoptosis and ferroptosis pathways. Electron microscopy observation, ICP-MS iron ion loading detection, and WB determination of protein GPX4 expression confirmed that HT22 cells undergo apoptosis, while bEnd3 cells undergo multiple pathways of iron death and apoptosis regulation. Furthermore, a linear regression model showed the interaction between maternal urine Pb levels, the rs9818496 site of the CCM3 SNP in peripheral blood DNA, and the concentration of the neurotransmitter metabolite 5-HIAA in maternal urine (F=4.198, P < 0.05). bEnd3 cells with CCM3 gene deficiency can induce HT22 cell apoptosis through iron death and apoptosis pathways under Pb exposure in a combined cell culture Pb exposure model, and CCM3 gene deficiency in endothelial cells and Pb exposure interacts with neural cell HT22. Epidemiological studies on maternal and newborn infants further confirmed the interaction between urine Pb levels in mothers and the SNP rs9818496 site of the CCM3 gene in peripheral blood DNA.

Single-Mode Control and Individual Nanoparticle Detection in the Ultraviolet Region Based on Boron Nitride Microdisk with Whispering Gallery Mode.

Optical microcavities are known for their strongly enhanced light-matter interactions. Whispering gallery mode (WGM) microresonators have important applications in nonlinear optics, single-mode output, and biosensing. However, there are few studies on resonance modes in the ultraviolet spectrum because most materials with high absorption properties are in the ultraviolet band. In this study, the performance of a microdisk cavity based on boron nitride (BN) was simulated by using the Finite-difference time-domain (FDTD) method. The WGM characteristics of a single BN microdisk with different sizes were obtained, wherein the resonance modes could be regulated from 270 nm to 350 nm; additionally, a single-mode at 301.5 nm is achieved by cascading multiple BN microdisk cavities. Moreover, we found that a BN microdisk with a diameter of 2 µm has a position-independent precise sensitivity for the nanoparticle of 140 nm. This study provides new ideas for optical microcavities to achieve single-mode management and novel coronavirus size screening, such as SARS-CoV-2, in the ultraviolet region.

Genomic insights and antimicrobial resistance profiles of CRKP and non-CRKP isolates in a Beijing geriatric medical center: emphasizing the blaKPC-2 carrying high-risk clones and their spread.

Background: The escalating resistance of Klebsiella pneumoniae, a prevalent pathogen in healthcare settings, especially its carbapenem-resistant K. pneumoniae (CRKP), to a wide array of antibiotics, notably ß-lactams, constitutes a formidable challenge for healthcare and global public health management. Methods: This research compared the resistance phenotypes and genomic profiles of CRKP and Non-CRKP isolates in a Beijing hospital, focusing on high-risk blaKPC-2 gene-bearing CRKP clones and the structure of mobile genetic elements facilitating their spread across hospital departments. Forty K. pneumoniae isolates were collected from various departments of the hospital and subjected to antimicrobial susceptibility testing and whole-genome sequencing to analyze their resistance phenotypes and genomic features. Results: The study revealed that among the 31 CRKP isolates, ST11 is the most common sequence type, with K47 and OL101 being the dominant capsule types, primarily observed in the respiratory department. In terms of antimicrobial susceptibility: 87.5% of the isolates exhibited multidrug resistance (MDR), with a high resistance rate of 30% against tigecycline. All CRKP isolates demonstrated resistance to multiple drug classes (≥5 CLSI classes). Non-CRKP isolates also showed high resistance rates to minocycline and doxycycline (77.8%). the ST11-KL47-OL101 type emerged as the predominant clone among the CRKP isolates carrying the blaKPC-2 gene. This dominance appears to be mediated by the pKpnR03_2 plasmid, which harbors not only blaKPC-2 and rmtb but also gene clusters pertinent to iron transport and arsenic resistance. These isolates, clustering in the C3 clade of the phylogenetic tree, exhibited minor genetic variations and close evolutionary relationships, suggesting a plasmid-driven spread across various hospital departments. Conclusion: In summary, our study highlights the extensive spread of antibiotic-resistant K. pneumoniae across various departments in our hospital, with a particular emphasis on the dominant clonal proliferation of the ST11-KL47-OL101 CRKP strain. This finding underscores the significant role of plasmid-mediated gene transfer in the evolution and dissemination of resistant strains within hospital environments. The study emphasizes the necessity for ongoing surveillance of antibiotic resistance and genomic analysis in hospital settings to effectively monitor and manage these challenges.

Drug-Loaded Bacillus Calmette-Guérin Bacteria for Immuno-Chemo Combo Therapy in Bladder Cancer.

Intravesical Bacillus Calmette-Guérin (BCG) is a well-established strategy for managing high-risk nonmuscle-invasive bladder cancer (NMIBC); however, over half of patients still experience disease recurrence or progression. Although the combined intravesical instillation of various chemotherapeutic drugs is implemented in clinical trials to enhance the BCG therapy, the outcome is far from satisfying due to severe irritative effects and treatment intolerance at high doses. Therefore, it is adopted the "biotin-streptavidin strategy" to doxorubicin (DOX)-encapsulated nanoparticles within live BCG bacteria (DOX@BCG) to improve treatment outcomes. Adherence of BCG to the bladder epithelium helps precisely target DOX@BCG to the local tumor cells and simultaneously increases intratumoral transport of therapeutic drugs. DOX@BCG effectively inhibits cancer progression and prolongs the survival of rats/mice with orthotopic bladder cancer owing to synergism between BCG-immunotherapy, DOX-chemotherapy, and DOX-induced immunogenic tumor cell death; furthermore, it exhibits improved tolerance and biosafety, and establishes antitumor immunity in the tumor microenvironment. Therefore, the drug-loaded live BCG bacterial delivery system holds considerable potential for clinical translation in the intravesical treatment of bladder cancer.

Causes of death and treatment-related mortality in newly diagnosed childhood acute lymphoblastic leukemia treatment with Chinese Children's Cancer Group study ALL-2015.

To investigate the possible risk factors for death at post-treatment in children with acute lymphoblastic leukemia (ALL). A multivariate competing risk analysis was performed to retrospectively analyze the data of children with ALL who died after treatment with CCCG-ALL-2015 in China and to determine the possible risk factors for death at post-treatment in children with ALL. Age at the first diagnosis of ≥10 years; final risk level of high-risk; D19 minimal residual disease (MRD) (≥0.01%) and D46 MRD (≥0.01%); genetic abnormalities, such as KMT2A-rearrangement, c-Myc rearrangement, and PDGFRB rearrangement; and the presence of CNS3 (all P values, <0.05) were identified as independent risk factors, whereas the risk level at the first diagnosis of low-risk (LR) and ETV6::RUNX1 positivity was considered as independent protective factors of death in children with ALL. Among the 471 cases of death, 45 cases were treated with CCCG-ALL-2015 only, and 163 (34.61%) were treatment-related, with 62.42% due to severe infections. 55.83% of treatment-related mortality (TRM) occurred in the early phase of treatment (induction phase). TRM has a significant impact on the overall survival of pediatric patients with ALL. Moreover, the CCCG-ALL-2015 regimen has a better safety profile for treating children with ALL, with rates close to those in developed countries (registration number: ChiCTR-IPR-14005706; date of registration: June 4, 2014).

Outdoor environmental exposome and the burden of tuberculosis: Findings from nearly two million adults in northwestern China.

We simultaneously assessed the associations for a range of outdoor environmental exposures with prevalent tuberculosis (TB) cases in a population-based health program with 1940,622 participants ≥ 15 years of age. TB status was confirmed through bacteriological and clinical assessment. We measured 14 outdoor environmental exposures at residential addresses. An exposome-wide association study (ExWAS) approach was used to estimate cross-sectional associations between environmental exposures and prevalent TB, an adaptive elastic net model (AENET) was implemented to select important exposure(s), and the Extreme Gradient Boosting algorithm was subsequently applied to assess their relative importance. In ExWAS analysis, 12 exposures were significantly associated with prevalent TB. Eight of the exposures were selected as predictors by the AENET model: particulate matter ≤ 2.5 µm (odds ratio [OR]=1.01, p = 0.3295), nitrogen dioxide (OR=1.09, p < 0.0001), carbon monoxide (OR=1.19, p < 0.0001), and wind speed (OR=1.08, p < 0.0001) were positively associated with the odds of prevalent TB while sulfur dioxide (OR=0.95, p = 0.0017), altitude (OR=0.97, p < 0.0001), artificial light at night (OR=0.98, p = 0.0001), and proportion of forests, shrublands, and grasslands (OR=0.95, p < 0.0001) were negatively associated with the odds of prevalent TB. Air pollutants had higher relative importance than meteorological and geographical factors, and the outdoor environment collectively explained 11% of TB prevalence.

[Expression and Clinical Significance of Exosome Derived MiR-181b-5p in Children with Acute Lymphoblastic Leukemia].

OBJECTIVE: To explore the expression level of exosome derived miR-181b-5p in different disease stages of children with acute lymphoblastic leukemia and its relationship with clinical characteristics. METHODS: Bone marrow plasma samples of 86 children with ALL were collected. Exosomes were extracted by exosome extraction kit, and RNA in exosomes was extracted by TRIzol method. The levels of miR-181b-5p in the blood plasma exosomes of the patients in the newly diagnosed group, relapse group, remission group and control group were detected by qRT- PCR. The difference of miR-181b-5p expression level in each group was compared and analyzed, and the relationship between miR-181b-5p expression level and clinical characteristics was analyzed. RESULTS: The expression level of exosomal miR-181b-5p in the newly diagnosed group and the relapsed group was significantly lower than that in the remission group and the control group (P< 0.05). The expression level of exosomal miR-181b-5p in T-ALL children was higher than that in B-ALL children (P<0.05). The expression level of plasma exosomal miR-181b-5p in male children was higher than that in female children (P<0.01). CONCLUSION: Exosome derived miR-181b-5p changes dynamically in the course of ALL children, and can be used as a marker miRNA to monitor disease status. Exosomes can transmit information in the tumor microenvironment and serve as a potential carrier for biomolecular targeted therapy.

Prolonged use of eltrombopag in patients with severe aplastic anemia in the real world.

Eltrombopag (EPAG) can improve the efficacy of immunosuppressive therapy (IST) consisting of antithymocyte immunoglobulin (ATG) and cyclosporin in severe aplastic anemia (SAA) patients. This study explored whether patients with SAA could benefit from continuous usage of EPAG beyond 6 months.Seventy-four treatment-naive Chinese patients with SAA were administrated with rabbit ATG-based IST plus EPAG for 6 months. Patients not achieving complete remission (CR) at 6 months were treated with EPAG for another 6 months.At 1, 3, 6 and 12 months after IST, the cumulative response rates were 31%, 61%, 82% and 90%, and the cumulative CR rates were 0, 14%, 27% and 45%, respectively. The cumulative effect curve showed that 93% and 53% of all remission and CR occurred within 6 months, while 98% and 83% of all remission and CR occurred within 12 months. Thirty-seven percent of patients (11 of 30) with partial remission (PR) at 6 months continuously exposed to EPAG improved to CR within 3 (1-5) months of the extended median time. Six patients failing at 6 months continued to use EPAG. Three patients showed improved responses with an extended median time of 6 (1-6) months. The 2-year event-free survival (EFS) was better in those continuing with EPAG (89% vs. 49%, P = 0.006) for patients with PR or non-remission at 6 months.Continuous administration with EPAG could improve the hematologic response and EFS in patients without achieving CR at 6 months.This trial has been registered at the Chinese Clinical Trial Registry (ChiCTR2100045895).

Interactive effects of molecular subtypes with tumor size and extracranial metastatic pattern on risk of brain metastasis in breast cancer patients: A population-based study.

BACKGROUND: Early detection of brain metastasis (BM) is essential for prognostic improvement in breast cancer (BC) patients. The aim was to identify predictors of BCBM in different molecular subtypes on a population-based level. METHODS: The Surveillance, Epidemiology, and End Results database was used to select BC patients diagnosed from 2010 to 2018. We evaluated the incidence and risk factors of BCBM and tested the interaction effects between molecular subtypes and other risk factors. RESULTS: Among the 527,525 selected patients, molecular subtypes significantly interacted with T stage and extracranial metastasis (ECM) patterns on the risk of BM in the whole BC population (interaction p = 0.002, <0.001, respectively) and after excluding patients with unknown states of key factors. BM development was independent of the T stage only in HR-/HER2- patients (trend p = 0.126). We selected BC patients with single-organ ECM and found a significant interaction between molecular subtypes and ECM patterns (interaction p = 0.013). The impact of ECM patterns on the risk of BM was limited to HR-/HER2- patients (trend p < 0.001), for whom using bone metastasis as a reference, lung metastasis increased the risk of BM (OR = 1.936, 95% CI: 1.300-2.882, p = 0.001). CONCLUSION: T stage and ECM patterns had different associations with BM in different molecular subtypes. HR-/HER2- BC had distinct features on BM development, manifested as a lack of tumor size effect and is associated with lung metastasis. Close surveillance for BM should be considered for HR-/HER2- BC patients.

A Shigella sonnei clone with extensive drug resistance associated with waterborne outbreaks in China.

Antimicrobial resistance of Shigella sonnei has become a global concern. Here, we report a phylogenetic group of S. sonnei with extensive drug resistance, including a combination of multidrug resistance, coresistance to ceftriaxone and azithromycin (cefRaziR), reduced susceptibility to fluoroquinolones, and even colistin resistance (colR). This distinct clone caused six waterborne shigellosis outbreaks in China from 2015 to 2020. We collect 155 outbreak isolates and 152 sporadic isolates. The cefRaziR isolates, including outbreak strains, are mainly distributed in a distinct clade located in global Lineage III. The outbreak strains form a recently derived monophyletic group that may have emerged circa 2010. The cefRaziR and colR phenotypes are attributed to the acquisition of different plasmids, particularly the IncB/O/K/Z plasmid coharboring the blaCTX-M-14, mphA, aac(3)-IId, dfrA17, aadA5, and sul1 genes and the IncI2 plasmid with an mcr-1 gene. Genetic analyses identify 92 accessory genes and 60 single-nucleotide polymorphisms associated with the cefRaziR phenotype. Surveillance of this clone is required to determine its dissemination and threat to global public health.

Identification of tree species based on the fusion of UAV hyperspectral image and LiDAR data in a coniferous and broad-leaved mixed forest in Northeast China.

Rapid and accurate identification of tree species via remote sensing technology has become one of the important means for forest inventory. This paper is to develop an accurate tree species identification framework that integrates unmanned airborne vehicle (UAV)-based hyperspectral image and light detection and ranging (LiDAR) data under the complex condition of natural coniferous and broad-leaved mixed forests. First, the UAV-based hyperspectral image and LiDAR data were obtained from a natural coniferous and broad-leaved mixed forest in the Maoer Mountain area of Northeast China. The preprocessed LiDAR data was segmented using a distance-based point cloud clustering algorithm to obtain the point cloud of individual trees; the hyperspectral image was segmented using the projection outlines of individual tree point clouds to obtain the hyperspectral data of individual trees. Then, different hyperspectral and LiDAR features were extracted, respectively, and the importance of the features was analyzed by a random forest (RF) algorithm in order to select appropriate features for the single-source and multi-source data. Finally, tree species identification in the study area were conducted by using a support vector machine (SVM) algorithm together with hyperspectral features, LiDAR features and fused features, respectively. Results showed that the total accuracy for individual tree segmentation was 84.62%, and the fused features achieved the best accuracy for identification of the tree species (total accuracy = 89.20%), followed by the hyperspectral features (total accuracy = 86.08%) and LiDAR features (total accuracy = 76.42%). The optimal features for tree species identification based on fusion of the hyperspectral and LiDAR data included the vegetation indices that were sensitive to the chlorophyll, anthocyanin and carotene contents in the leaves, the partial components of the transformed independent component analysis (ICA), minimum noise fraction (MNF) and principal component analysis (PCA), and the intensity features of the LiDAR echo, respectively. It was concluded that the framework developed in this study was effective in tree species identification under the complex conditions of natural coniferous and broad-leaved mixed forest and the fusion of UAV-based hyperspectral image and LiDAR data can achieve enhanced accuracy compared the single-source UAV-based remote sensing data.

Whole transcriptome sequencing reveals a TCF4-ZNF384 fusion in acute lymphoblastic leukemia.

Previous studies have shown that, the clinical features and prognosis of ZNF384-rearranged pediatric acute lymphoblastic leukemia (ALL) depend on its translocation partners. We report two cases of TCF4-ZNF384 fusion, one 6-year-old girl and one 10-year-old boy, both diagnosed by whole-transcriptome sequencing, and TCF4 is the newest fusion partner of ZNF384. As illustrated in this first report of TCF4-ZNF384 fusion in ALL patients, the identification of patients with ZNF384 rearrangement in ALL patients is critical to elucidate outcomes associated with a specific rearrangement and to develop appropriate treatment strategies. In addition, the development of other methods to detect ZNF384 specific translocation partners and leukemia specific targeting agents is of great significance to further improve the prognosis of ALL with ZNF384-rearrangement.

Collaboration between meteorology and public health: Predicting the dengue epidemic in Guangzhou, China, by meteorological parameters.

Background: Dengue has become an increasing public health threat around the world, and climate conditions have been identified as important factors affecting the transmission of dengue, so this study was aimed to establish a prediction model of dengue epidemic by meteorological methods. Methods: The dengue case information and meteorological data were collected from Guangdong Provincial Center for Disease Prevention and Control and Guangdong Meteorological Bureau, respectively. We used spatio-temporal analysis to characterize dengue epidemics. Spearman correlation analysis was used to analyze the correlation between lagged meteorological factors and dengue fever cases and determine the maximum lagged correlation coefficient of different meteorological factors. Then, Generalized Additive Models were used to analyze the non-linear influence of lagged meteorological factors on local dengue cases and to predict the number of local dengue cases under different weather conditions. Results: We described the temporal and spatial distribution characteristics of dengue fever cases and found that sporadic single or a small number of imported cases had a very slight influence on the dengue epidemic around. We further created a forecast model based on the comprehensive consideration of influence of lagged 42-day meteorological factors on local dengue cases, and the results showed that the forecast model has a forecast effect of 98.8%, which was verified by the actual incidence of dengue from 2005 to 2016 in Guangzhou. Conclusion: A forecast model for dengue epidemic was established with good forecast effects and may have a potential application in global dengue endemic areas after modification according to local meteorological conditions. High attention should be paid on sites with concentrated patients for the control of a dengue epidemic.

An outbreak of acute respiratory disease caused by HAdV-55 in Beijing, China, 2020.

Human adenoviruses (HAdVs) can cause acute respiratory diseases (ARDs) worldwide, and HAdV-55 is a reemergent pathogen in recent years. In the study, we investigated an outbreak of ARD at a school due to HAdV-55 in Beijing, China, during the early outbreak of coronavirus disease 2019 (COVID-19). The epidemic prevention team was dispatched to the school to collect epidemiologic data and nasopharyngeal samples. Then, real-time reverse transcription polymerase chain reaction (PCR) and multiplex PCR assays were used to detect severe acute respiratory syndrome coronavirus 2 and other respiratory pathogens, respectively. One representative HAdV-55 isolate was selected and submitted for whole-genome sequencing using a MiSeq system and the whole-genome phylogenetic tree was conducted based on the maximum likelihood method. The outbreak lasted from January 27 to February 6, 2020, and 108 students developed fever, among whom 60 (55.56%) cases were diagnosed with HAdV-55 infection in the laboratory using real-time PCR and 56 cases were hospitalized. All the confirmed cases had a fever and 11 cases (18.33%) presented with a fever above 39°C. Other main clinical symptoms included sore throat (43.33%) and headache (43.33%). We obtained and assembled the full genome of one isolate, BJ-446, with 34 761 nucleotides in length. HAdV-55 isolate BJ-446 was 99.85% identical to strain QS-DLL, which was the first HAdV-55 strain in China isolated from an ARD outbreak in Shanxi in 2006. One and four amino acid mutations were observed in the hexon gene and the coding region of L2 pV 40.1 kDa protein, respectively. We identified the first HAdV-55 infection associated with the ARD outbreak in Beijing since the emergence of COVID-19. The study suggests that improved surveillance of HAdV is needed, although COVID-19 is still prevalent in the world.

Adenoviral Vector for Enhanced Prostate Cancer Specific Transferrin Conjugated Drug Targeted Therapy.

Prostate cancer (PCa) is one of the leading causes of death for men worldwide. Unlike some other types of cancer, there is a lack of targeted therapy for prostate cancer patients that can kill cancer cells but do much less damage to the normal tissue. In this paper, we report on an adenoviral vector enhanced prostate cancer specific transferrin conjugated drug targeted therapy. In particular, a functional PCa-specific gene probe is introduced to drive and up-regulate the transferrin receptor expression on the PCa via adenoviral vector. As a result, significantly enhanced accumulation of nanoscale transferrin-doxorubicin (Tf-DOX) protein drug conjugates and concomitant notably elevated PCa tumor inhibition are observed. This conceptual strategy provides the proof-of-concept for the targeted therapy of PCa that is highly desired but not yet developed.

[Single Center Clinical Analysis of Bloodstream Infection Pathogens in Children with Acute Leukemia].

OBJECTIVE: To investigate the clinical features, distribution of pathogenic bacteria, and drug resistance of bloodstream infection in children with acute leukemia. METHODS: Clinical data of 93 blood culture-positive children with acute leukemia from January 2015 to December 2019 in Department of Pediatrics, The Second Hospital of Anhui Medical University were analyzed retrospectively. RESULTS: In these 93 cases, 78 cases were in the period of neutrophil deficiency. There were 54 Gram-negative bacteria (G-) (58.1%) found through blood culture, and the top 4 strains were Escherichia coli (15.1%), Klebsiella pneumoniae (13.9%), Pseudomonas aeruginosa (6.5%), and Enterobacter cloacae (6.5%). There were 39 Gram-positive bacteria (G+) (41.9%) detected, and the top 4 strains were Staphylococcus epidermidis (10.8%), Streptococcus pneumoniae (6.5%), Staphylococcus hemolyticus (5.4%), and Staphylococcus human (5.4%). Among 74 strains of pathogenic bacteria from acute lymphoblastic leukemia (ALL) children, there were 29 strains of G+ bacteria (39.2%) and 45 strains of G- bacteria (60.8%). While in 19 strains from acute myeloblastic leukemia (AML) patients, G- bacteria accounted for 47.4% and G+ bacteria accounted for 52.6%. In 15 ALL children without neutropenia, G+ bacteria made up the majority of the strains (66.7%). In the 93 strains of pathogenic bacteria, 13 (13.9%) strains were multidrug-resistant. Among them, extended-spectrum ß-lactamases accounted for 42.9%, carbapenemase-resistant enzyme Klebsiella pneumoniae 15.4%, and carbapenemase-resistant enzyme Enterobacter cloacae strains 33.3%, which were detected from G- bacteria. While, 13.3% of methicillin-resistant coagulase-negative Staphylococci accounted for 13.3% detected from G+ bacteria, but linezolid, vancomycin, teicoplanin Staphylococcus and Enterococcus resistant were not found. The average procalcitonin (PCT) value of G- bacteria infection was (11.02±20.282) ng/ml, while in G+ infection it was (1.81±4.911) ng/ml, the difference was statistically significant (P<0.05). The mean value of C-reactive protein (CRP) in G- infection was (76.33±69.946) mg/L, and that in G+ infection was (38.34±57.951) mg/L. The prognosis of active treatment was good, and only one case died of septic shock complicated with disseminated intravascular coagulation (DIC) and gastrointestinal bleeding caused by carbapenemase-resistant enzyme enterobacteriaceae. CONCLUSION: G- is the major bacteria in acute leukemia children with bloodstream infection, but the distribution of ALL and AML strains is different. G- bacteria dominates in ALL, while G+ bacteria and G- bacteria are equally distributed in AML. Non-agranulocytosis accompanied by bloodstream infections is dominant by G+ bacteria. The mean value of PCT and CRP are significantly higher in G- bacteria infection than in G+ bacteria.

Corrigendum: A Severe Gastroenteritis Outbreak of Salmonella enterica Serovar Enteritidis Linked to Contaminated Egg Fried Rice, China, 2021.

[This corrects the article DOI: 10.3389/fmicb.2021.779749.].