Clinical characteristics and prognosis of SARS-CoV-2 infection in children with hematological malignancies: A multicenter, retrospective study in China.

BACKGROUND: Data on SARSCoV-2 infection in children with hematological malignancies (HM) are limited. Here, we describe the clinical features of children with HM after SARS-CoV-2 infection and investigate the potential risk factors for disease severity. METHODS: Children with HM and SARS-CoV-2 infection from five hospitals in five cities in Henan, China from October 2022 to January 2023 were retrospectively included. Clinical information and Coronavirus disease 2019 (COVID-19) vaccination status were collected for further analyses. RESULTS: A total of 285 children with HM and SARS-CoV-2 infections were included. COVID-19 was asymptomatic in 3.2% of the patients (n = 9), mild in 89.1% (n = 254), moderate in 5.3% (n = 15), severe in 1.8% (n = 5), and critical in 0.7% (n = 2). Fever (92.4%) and cough (56.9%) were the most common symptoms. Most (249, 88.3%) children were managed at home during their COVID-19 illness. Of the 36 children admitted to the hospital, two required intensive care unit care, 11 required supplementary oxygen, and two non-invasive ventilation. A total of 283 (99.3%) children fully recovered and two (0.7%) died due to COVID-19. Significant risk factors for increased severity of infection in multivariable analyses were the presence of comorbidity (OR, 10.4; 95%CI, 2.8-38.7; p < 0.0001), neutropenia (OR, 10.4; 95%CI, 2.6-41.8; p = 0.001), and lymphopenia (OR, 4.2; 95%CI, 1.2-15.4; p = 0.029). A total of 30.9% (88/285) of the children received at least one dose of the inactivated COVID-19 vaccine at COVID-19 diagnosis. Compared with children who received at least one dose of the COVID-19 vaccine, fever was significantly more common in unvaccinated children (79.3% vs. 93.8%, p < 0.001). CONCLUSIONS: Children with HM are not at an increased risk of severe COVID-19 compared to the general pediatric population. However, comorbidities such as lymphopenia and neutropenia may increase the risk of developing moderate or severe/critical disease. Our data may help in management decisions for this vulnerable population.

Risk factors and prognosis for latent tuberculosis infection in dialysis patients: A retrospective cohort study at a single tertiary care center.

INTRODUCTION: Recent studies report that latent tuberculosis infection (LTBI) may lead to an increased risk of cardiovascular disease (CVD) that led us to hypothesize that LTBI may play an important role in major adverse cardiovascular events (MACE) in dialysis patients. METHODS: A single-center retrospective cohort study was conducted. A total of 270 patients undergoing hemodialysis or peritoneal dialysis more than 3 months were included. The interferon enzyme-linked immunospot (IFN-γ ELISPOT) assay was used for the diagnosis of LTBI. Primary endpoints were MACE, including all-cause death and acute coronary syndrome (ACS). The association between LTBI and MACE was examined using multivariate Cox proportional hazards regression after adjusting for covariates and Kaplan-Meier survival analysis. RESULTS: In our study, the patients were classified into LTBI (n = 47) or non-LTBI (n = 223) groups. Independent risk factors for LTBI in dialysis population were prior tuberculosis (TB) history (odds ratio [OR] 4.817 [1.064-22.306]), tobacco use (OR 2.903 [1.155-7.299]), and older age (OR 1.027 [1.002-1.053]). After a median follow-up of 39 months, the incidence of active TB was 6.4% versus 0% in dialysis patients with and without LTBI, respectively (p = 0.005). Multivariate Cox analysis showed that LTBI was significantly associated with MACE (hazard ratio [HR] 2.540 [1.490-4.350]) after adjustment for potential confounders. CONCLUSIONS: Prior TB history, tobacco use, and the elderly can be used to select cost-effective LTBI screening target groups in dialysis patients. LTBI is not only closely related to active TB but also an independent risk factor for higher incidence of MACE in dialysis population.

Antibacterial properties of hexanal-chitosan nanoemulsion against Vibrio parahaemolyticus and its application in shelled shrimp preservation at 4 °C.

Vibrio parahaemolyticus has been considered as the leading pathogen associated with seafood-borne disease. Hexanal possesses antibacterial property but the hydrophobicity and volatility limit its application. The purpose of this study was to prepare hexanal-chitosan nanoemulsion (HCN), investigate its antibacterial ability against V. parahaemolyticus, and examine the combination of HCN with sodium alginate coating on the quality attributes of shrimp during cold storage. The mean droplet size of HCN fabricated by ultrasonic emulsification was 91.28 nm. HCN showed regular spherical shape and exhibited good centrifugation stability and storage stability at 4 °C. HCN exerted anti-V. parahaemolyticus effect with the minimum inhibitory concentration and minimal bactericidal concentration of both 5 mg/mL. Furthermore, HCN induced morphological changes and destroyed bacterial membrane, resulting in cell death. The results of preservation test showed that HCN alone and its combination with sodium alginate coating effectively retarded the quality deterioration and microbial spoilage of shelled shrimps during refrigerated storage. Comparatively, the combination treatment exhibited better preservation effect. The present study suggested that HCN prepared by ultrasonic emulsification is an effective alternative to control V. parahaemolyticus contamination in seafood and also shows great application potential in the quality maintaining of seafood during cold storage.

The combination model of CNN and GCN for machine fault diagnosis.

Learning powerful discriminative features is the key for machine fault diagnosis. Most existing methods based on convolutional neural network (CNN) have achieved promising results. However, they primarily focus on global features derived from sample signals and fail to explicitly mine relationships between signals. In contrast, graph convolutional network (GCN) is able to efficiently mine data relationships by taking graph data with topological structure as input, making them highly effective for feature representation in non-Euclidean space. In this article, to make good use of the advantages of CNN and GCN, we propose a graph attentional convolutional neural network (GACNN) for effective intelligent fault diagnosis, which includes two subnetworks of fully CNN and GCN to extract the multilevel features information, and uses Efficient Channel Attention (ECA) attention mechanism to reduce information loss. Extensive experiments on three datasets show that our framework improves the representation ability of features and fault diagnosis performance, and achieves competitive accuracy against other approaches. And the results show that GACNN can achieve superior performance even under a strong background noise environment.

TMT-Based Quantitative Proteomics and Non-targeted Metabolomic Analyses Reveal the Antibacterial Mechanism of Hexanal against Vibrio parahaemolyticus.

Hexanal is a phytochemical with antimicrobial activity. However, its antibacterial effect and mechanism against Vibrio parahaemolyticus (V. parahaemolyticus) remain unclear. The study aims to elucidate the associated mechanism using tandem mass tag quantitative proteomics and non-targeted metabolomics. Hexanal treatment reduced intracellular ATP concentration, increased membrane permeability, and destroyed the morphology and ultrastructure of V. parahaemolyticus cells. Proteomics and metabolomics data indicated that 572 differentially expressed proteins (DEPs) and 241 differential metabolites (DMs) were identified in hexanal-treated V. parahaemolyticus. These DEPs and DMs were involved in multiple biological pathways including amino acid metabolism, purine and pyrimidine biosynthesis, etc. Bioinformatics analysis revealed that hexanal damaged the structure and function of cell membranes, inhibited nucleotide metabolism, and disturbed carbohydrate metabolism and tricarboxylic acid cycle (TCA) cycle, which ultimately resulted in growth inhibition and bacterial death. The study is conducive to better understand the mode of action of hexanal against V. parahaemolyticus and offers experimental foundation for the application of hexanal as the antibacterial agent in the seafood-associated industry.

A study on pick cutting properties with full-scale rotary cutting experiments and numerical simulations.

To investigate the cutting forces on road-header picks, a series of full-scale single-pick rotary cutting tests on sandstone samples were conducted at the National Engineering Laboratory of Coal Mining Machinery and Equipment, China. The primary objective of this study is to optimize the cut spacing and to verify the numerical simulation results. Cutting forces are investigated under different cutting depths and cut spacings. Cut spacing is optimized by analyzing the specific energy, coarseness index, and cutting force. The rock cutting process is simulated on a pick model using the PFC3D software. Rock samples are used as models, and particle assemblies and micro-properties are calibrated by uniaxial compressive strength tests and Brazilian disc tensile strength tests. The optimum ratio of cut spacing to cutting depth for the analyzed sandstone is determined to be in the range of 3 to 4. The experimental results show that a higher coarseness index corresponds to an increased block ratio, and specific energy decreases under optimum cutting conditions. Forces acting on the pick model are determined by simulation. A reasonable agreement exists between the experimental and numerical simulation results regarding the pick forces. The influence of the cut spacing on the rock-breaking effect observed in the experiments is confirmed by numerical simulations. Therefore, numerical simulations using the PFC3D software represent a reliable method for predicting the pick forces.

Inhibitory effects of lactobionic acid on Vibrio parahaemolyticus planktonic cells and biofilms.

Vibrio parahaemolyticus is the primary pathogenic bacteria associated with seafood-borne illnesses. Lactobionic acid (LBA) is an organic acid with multiple biological activities that has recently been a focus of interest as an antibacterial agent. The aim of this study was to investigate the inhibitory effects of LBA on Vibrio parahaemolyticus planktonic cells and biofilms. The minimum inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of LBA against Vibrio parahaemolyticus were both identified as 4 mg/mL. LBA exerted antimicrobial effects against planktonic Vibrio parahaemolyticus cells by damaging their membranes, as revealed by reduced intracellular ATP concentrations, increased protein leakage, abnormal cell morphology and diminished membrane integrity after treatment. At 1/16 × MIC and 1/8 × MIC, LBA inhibited biofilm formation and downregulated the expression of some biofilm-related genes, which was confirmed by crystal violet staining, field-emission scanning electron microscopy (FESEM) observations, and real-time quantitative PCR analysis. Moreover, LBA inactivated Vibrio parahaemolyticus cells within biofilms (on polystyrene and stainless steel surfaces), destroyed biofilm structures on stainless steel surfaces, and also reduced the levels of polysaccharides and proteins in the biofilms. Therefore, LBA is a potential low-cost agent that can be used to control planktonic Vibrio parahaemolyticus and its biofilms.

Value of gamma interferon enzyme-linked immunospot assay in the diagnosis of peritoneal dialysis-associated tuberculous peritonitis.

BACKGROUND: Tuberculous peritonitis is the most common form of extrapulmonary tuberculosis infection in peritoneal dialysis patients. However, diagnosing tuberculous peritonitis quickly and early has always been a challenge for nephrologists. Mycobacterium tuberculosis antigen-specific gamma interferon enzyme-linked immunospot (IFN-γ ELISPOT) assay has been widely used in the clinical diagnosis of tuberculous pleurisy and peritonitis, but its use has not been reported for uremia. METHODS: This study mainly verified the feasibility of using the M. tuberculosis antigen-specific IFN-γ ELISPOT assay in the diagnosis of continuous ambulatory peritoneal dialysis (CAPD) patients with tuberculous peritonitis. Taking M. tuberculosis culture as the gold standard, the IFN-γ ELISPOT assay was used to analyze peripheral blood and peritoneal dialysis fluid of patients, and the receiver operating characteristic (ROC) curves in patients with tuberculous peritonitis (TBP) or non-tuberculous peritonitis (NTBP) were analyzed. RESULTS: The area under the receiver operating characteristic curve (AUC) was 0.927 (95% CI 0.816-1.000, P = 0.001) for the ELISPOT assay with peritoneal fluid mononuclear cells (PFMC), which was higher than that for the ELISPOT assay with peripheral blood mononuclear cells (PBMC) (0.825, 95% CI 0.6490-1.000, P = 0.011). The cutoff value for the diagnosis of TBP was 40 spot-forming cells (SFCs)/2 × 105 for the ELISPOT with PBMC, with a sensitivity of 55.6%, a specificity of 92.3%, and a diagnostic efficiency of 77.3%. The cutoff value for the diagnosis of TBP was 100 SFCs/2 × 105 for the ELISPOT on PFMC, with a sensitivity, specificity, and diagnostic efficiency 77.8%, 84.6%, and 81.8%, respectively. Parallel and serial testing algorithms appeared more accurate than single ELISPOT assays with PBMC, but ELISPOT assays with PFMC. CONCLUSIONS: The IFN-γ release test can be used for the early diagnosis of CAPD-related TBP; compared with peripheral blood, peritoneal fluid may be a more effective and accurate medium to diagnose CAPD complicated with tuberculous peritonitis.

dCubilin- or dAMN-mediated protein reabsorption in Drosophila nephrocytes modulates longevity.

Aging is a multifaceted process regulated by multiple cellular pathways, including the proteostasis network. Pharmacological or genetic enhancement of the intracellular proteostasis network extends lifespan and prevents age-related diseases. However, how proteostasis is regulated in different tissues throughout the aging process remains unclear. Here, we show that Drosophila homologs of Cubilin- and Amnionless (dCubilin and dAMN, respectively)-mediated protein reabsorption (CAMPR) from hemolymph insect blood by nephrocytes modulate longevity through regulating proteostasis in muscle and brain tissues. We find that overexpression of dAMN receptor in nephrocytes extends lifespan, whereas nephrocyte-specific dCubilin or dAMN RNAi knockdown shortens lifespan. We also show that CAMPR in nephrocytes regulates proteostasis in hemolymph and improves healthspan. In addition, we show that enhanced CAMPR in nephrocytes slows down the aging process in muscle and brain by maintaining the proteostasis network in these tissues. Altogether, our work has revealed an inter-organ communication network across nephrocytes and muscle/neuronal tissue that is essential for maintaining proteostasis, and to delay senescence in these organs. These findings provide insight into the role of renal protein reabsorption in the aging process via this tele-proteostasis network.

Inactivation Effect of Thymoquinone on Alicyclobacillus acidoterrestris Vegetative Cells, Spores, and Biofilms.

Alicyclobacillus acidoterrestris (A. acidoterrestris), a spore-forming bacterium, has become a main challenge and concern for the juices and acid beverage industry across the world due to its thermo-acidophilic characteristic. Thymoquinone (TQ) is one of the active components derived from Nigella sativa seeds. The objective of this study was to investigate antibacterial activity and associated molecular mechanism of TQ against A. acidoterrestris vegetative cells, and to evaluate effects of TQ on A. acidoterrestris spores and biofilms formed on polystyrene and stainless steel surfaces. Minimum inhibitory concentrations of TQ against five tested A. acidoterrestris strains ranged from 32 to 64 µg/mL. TQ could destroy bacterial cell morphology and membrane integrity in a concentration-dependent manner. Field-emission scanning electron microscopy observation showed that TQ caused abnormal morphology of spores and thus exerted a killing effect on spores. Moreover, TQ was effective in inactivating and removing A. acidoterrestris mature biofilms. These findings indicated that TQ is promising as a new alternative to control A. acidoterrestris and thereby reduce associated contamination and deterioration in the juice and acid beverage industry.

Antimicrobial and anti-biofilm activity of thymoquinone against Shigella flexneri.

Shigella flexneri (Sh. flexneri), a common foodborne pathogen, has become one of the main threats to food safety and human health due to its high pathogenicity and persistent infection. The objective of this study was to explore the antimicrobial and anti-biofilm activities and the possible mechanism of thymoquinone (TQ) against Sh. flexneri. The minimum inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of TQ against Sh. flexneri were 0.4 and 0.5 mg/mL, respectively. TQ showed bactericidal activity against Sh. flexneri in culture medium and milk system. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) observations demonstrated that TQ could induce abnormal cell morphology and destroy cell membrane. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis suggested that TQ could inhibit protein synthesis in Sh. flexneri. Also, at sub-inhibitory concentrations (SICs), TQ exhibited an inhibitory effect on Sh. flexneri biofilm formation, which was confirmed by crystal violet quantitative analysis and SEM observation. Real-time quantitative PCR (RT-qPCR) analyses revealed that TQ downregulated the expression of genes involved in Sh. flexneri biofilm formation. Thus, TQ has potential as a natural antimicrobial and anti-biofilm agent to address the contamination and infection caused by Sh. flexneri. KEY POINTS: • Antimicrobial and anti-biofilm activity of TQ on Shigella flexneri were investigated. • TQ inhibited biofilm formation by Shigella flexneri. • TQ provided a new strategy for Shigella flexneri control.

Efficient circular gene knockout system for Burkholderiales strain DSM 7029 and Mycobacterium smegmatis mc2 155.

Multiple gene knockouts are often employed in studies of microbial physiology and genetics. However, the selective markers that confer antibiotic resistance are generally limited, so it is necessary to remove these resistance genes before the next round of using, which is time consuming and labor intensive. Here, we created a universal circular gene knockout system for both the gram-negative bacterial Burkholderiales strain DSM 7029 and the gram-positive bacterial Mycobacterium smegmatis mc2 155, by combining the homologous recombination with multiple serine integrase-meditated site-specific recombination systems. In this system, a resistance gene and an integrase gene were constructed within the two attachment sites corresponding to a second, different integrase to form a cassette for gene disruption, which could be easily removed by the second integrase during the subsequent round of gene knockout. The sacB gene was also employed for negative selection. As the integrase-mediated deletion of the resistance/integrase gene cassette was highly efficient and concurrent with the following knockout round, the cyclic use of three cassettes could achieve multiple gene knockout in a sequential manner. Following the modularity concept in synthetic biology, common components of the knockout plasmids were retained as BioBricks, accelerating the knockout plasmids construction process. The circular gene knockout system can also be used for multiple gene insertions and applied to other microorganisms.

Inhibitory Effect of Coenzyme Q0 on the Growth of Staphylococcus aureus.

Coenzyme Q0 (CoQ0), one of benzoquinone compounds, has been demonstrated to possess antineoplastic, anti-inflammatory and antioxidant activities. However, its antimicrobial effect has not been extensively reported. In this study, antimicrobial activity of CoQ0 against Staphylococcus aureus was evaluated by measurement of inhibition zone, minimum inhibitory concentration (MIC), and growth curves. Time-kill assay was performed to assess the bactericidal activity of CoQ0 against S. aureus in tryptone soya broth and pasteurized milk. The possible mechanism of action was explored through measuring changes in intracellular ATP concentrations, membrane potential, and cell morphology. Furthermore, propidium iodide (PI) staining assay was performed to evaluate the effect of CoQ0 on cell membrane integrity. The MIC of CoQ0 against tested strains ranged from 7.8 to 62.5 µg/mL. CoQ0 at 2 × MIC showed bactericidal effect on S. aureus in tryptic soy broth (TSB) and pasteurized milk. Decrease in intracellular ATP concentration and membrane potential were detected when cells were treated with CoQ0. PI staining demonstrated destruction of bacterial cell membrane. CoQ0 also induced abnormal cell morphological changes, as confirmed by field emission scanning electron microscopy. These findings suggested that CoQ0 exhibited antimicrobial effect on S. aureus, which was partly because of its ability to damage cell membrane.

Immune Thrombocytopenic Purpura in Children of Eastern Henan Province, China.

In this retrospective cohort study conducted in 63 children with idiopathic thrombocytopenic purpura (ITP) in China; petechiae, bruises and bleeding were the major presentations. Most cases required therapy with one/more treatment options.