SLM Magnesium Alloy Micro-Arc Oxidation Coating.

In this study, we utilized Selective Laser Melting (SLM) technology to fabricate a magnesium alloy, and subsequently subject it to micro-arc oxidation treatment. We analyzed and compared the microstructure, elemental distribution, wetting angle, and corrosion resistance of the SLM magnesium alloy both before and after the micro-arc oxidation process. The findings indicate that the SLM magnesium alloy exhibits surface porosity defects ranging from 2% to 3.2%, which significantly influence the morphology and functionality of the resulting film layer formed during the micro-arc oxidation process. These defects manifest as pores on the surface, leading to an uneven distribution of micropores with varying sizes across the layer. The surface roughness of the 3D-printed magnesium alloy exhibits a high roughness value of 180 nanometers. The phosphorus (P) content is lower within the film layer compared to the surface, suggesting that the Mg3(PO4)2 phase predominantly resides on the surface, whereas the interior is primarily composed of MgO. The micro-arc oxidation process enhances the hydrophilicity and corrosion resistance of the SLM magnesium alloy, thereby potentially endowing it with bioactivity. Additionally, the increased surface roughness post-treatment promotes cell proliferation. However, certain inherent defects present in the SLM magnesium alloy samples negatively impact the improvement of their corrosion resistance.

Potent and broad HIV-1 neutralization in fusion peptide-primed SHIV-infected macaques.

An antibody-based HIV-1 vaccine will require the induction of potent cross-reactive HIV-1-neutralizing responses. To demonstrate feasibility toward this goal, we combined vaccination targeting the fusion-peptide site of vulnerability with infection by simian-human immunodeficiency virus (SHIV). In four macaques with vaccine-induced neutralizing responses, SHIV infection boosted plasma neutralization to 45%-77% breadth (geometric mean 50% inhibitory dilution [ID50] ∼100) on a 208-strain panel. Molecular dissection of these responses by antibody isolation and cryo-electron microscopy (cryo-EM) structure determination revealed 15 of 16 antibody lineages with cross-clade neutralization to be directed toward the fusion-peptide site of vulnerability. In each macaque, isolated antibodies from memory B cells recapitulated the plasma-neutralizing response, with fusion-peptide-binding antibodies reaching breadths of 40%-60% (50% inhibitory concentration [IC50] < 50 µg/mL) and total lineage-concentrations estimates of 50-200 µg/mL. Longitudinal mapping indicated that these responses arose prior to SHIV infection. Collectively, these results provide in vivo molecular examples for one to a few B cell lineages affording potent, broadly neutralizing plasma responses.

The vitamin D receptor is essential for the replication of pseudorabies virus.

The vitamin D receptor (VDR) is a nuclear steroid receptor that regulates the expression of genes across various biological functions. However, the role of VDR in pseudorabies virus (PRV) infection has not yet been explored. We discovered that VDR positively influenced PRV proliferation because knockdown of VDR impaired PRV proliferation, whereas its overexpression promoted it. Additionally, we observed that PRV infection upregulated VDR transcription alongside 1,25-dihydroxyvitamin D3 (VD3) synthesis, contingent on p53 activation. Furthermore, VDR knockdown hindered PRV-induced lipid synthesis, implicating VDR's involvement in this process. To decipher the mechanism behind VDR's stimulation of lipid synthesis during PRV infection, we conducted RNA sequencing (RNA-seq) and found significant enrichment of genes in the Ca2+ signaling pathway. Measurements of Ca2+ indicated that VDR facilitated Ca2+ absorption. Moreover, the PI3K/AKT/mTORC1 and AMPK/mTORC1 pathways were also enriched in our RNA-seq data. Interfering with VDR expression, or chelating Ca2+ using BAPTA-AM, markedly impacted the activation of PI3K/AKT/mTORC1 and AMPK/mTORC1 pathways, lipid synthesis, and PRV proliferation. In summary, our study demonstrates that PRV infection promotes VDR expression, thereby enhancing Ca2+ absorption and activating PI3K/AKT/mTORC1- and AMPK/mTORC1-mediated lipid synthesis. Our findings offer new insights into strategies for PRV prevention.IMPORTANCEVitamin D, beyond its well-known benefits for bone health and immune function, also plays a pivotal role in regulating gene expression through its receptor, the vitamin D receptor (VDR). Although VDR's influence spans multiple biological processes, its relationship with viral infections, particularly pseudorabies virus (PRV), remains underexplored. Our research illustrates a complex interplay where PRV infection boosts VDR expression, which in turn enhances Ca2+ absorption, leading to the activation of critical lipid synthesis pathways, PI3K/AKT/mTORC1 and AMPK/mTORC1. These findings not only deepen our understanding of the intricate dynamics between host molecular mechanisms and viral proliferation but also open avenues for exploring new strategies aimed at preventing PRV infection. By targeting components of the VDR-related signaling pathways, we can potentially develop novel therapeutic interventions against PRV and possibly other similar viral infections.

Decoding the origins, spread, and global risks of mcr-9 gene.

BACKGROUND: The global spread of the plasmid-mediated mcr (mobilized colistin resistance) gene family presents a significant threat to the efficacy of colistin, a last-line defense against numerous Gram-negative pathogens. The mcr-9 is the second most prevalent variant after mcr-1. METHODS: A dataset of 698 mcr-9-positive isolates from 44 countries is compiled. The historical trajectory of the mcr-9 gene is reconstructed using Bayesian analysis. The effective reproduction number is used innovatively to study the transmission dynamics of this mobile-drug-resistant gene. FINDINGS: Our investigation traces the origins of mcr-9 back to the 1960s, revealing a subsequent expansion from Western Europe to the America and East Asia in the late 20th century. Currently, its transmissibility remains high in Western Europe. Intriguingly, mcr-9 likely emerged from human-associated Salmonella and exhibits a unique propensity for transmission within the Enterobacter. Our research provides a new perspective that this host preference may be driven by codon usage biases in plasmids. Specifically, mcr-9-carrying plasmids prefer the nucleotide C over T compared to mcr-1-carrying plasmids among synonymous codons. The same bias is seen in Enterobacter compared to Escherichia (respectively as their most dominant genus). Furthermore, we uncovered fascinating patterns of coexistence between different mcr-9 subtypes and other resistance genes. Characterized by its low colistin resistance, mcr-9 has used this seemingly benign feature to silently circumnavigate the globe, evading conventional detection methods. However, colistin-resistant Enterobacter strains with high mcr-9 expression have emerged clinically, implying a strong risk of mcr-9 evolving into a global "true-resistance-gene". INTERPRETATION: This study explores the mcr-9 gene, emphasizing its origin, adaptability, and dissemination potential. Given the high mcr-9 expression colistin-resistant strains was observed in clinically the prevalence of mcr-9 poses a significant challenge to drug resistance prevention and control within the One Health framework. FUNDING: This work was partially supported by the National Natural Science Foundation of China (Grant No. 32141001 and 81991533).

Causal Association of Golgi Protein 73 With Coronary Artery Disease: Evidence from Proteomics and Mendelian Randomization.

Background: Identification of the unknown pathogenic factor driving atherosclerosis not only enhances the development of disease biomarkers but also facilitates the discovery of new therapeutic targets, thus contributing to the improved management of coronary artery disease (CAD). We aimed to identify causative protein biomarkers in CAD etiology based on proteomics and 2-sample Mendelian randomization (MR) design. Methods: Serum samples from 33 first-onset CAD patients and 31 non-CAD controls were collected and detected using protein array. Differentially expressed analyses were used to identify candidate proteins for causal inference. We used 2-sample MR to detect the causal associations between the candidate proteins and CAD. Network MR was performed to explore whether metabolic risk factors for CAD mediated the risk of identified protein. Vascular expression of candidate protein in situ was also detected. Results: Among the differentially expressed proteins identified utilizing proteomics, we found that circulating Golgi protein 73 (GP73) was causally associated with incident CAD and other atherosclerotic events sharing similar etiology. Network MR approach showed low-density lipoprotein cholesterol and glycated hemoglobin serve as mediators in the causal pathway, transmitting 42.1% and 8.7% effects from GP73 to CAD, respectively. Apart from the circulating form of GP73, both mouse model and human specimens imply that vascular GP73 expression was also upregulated in atherosclerotic lesions and concomitant with markers of macrophage and phenotypic switching of vascular smooth muscle cells (VSMCs). Conclusions: Our study supported GP73 as a biomarker and causative for CAD. GP73 may involve in CAD pathogenesis mainly via dyslipidemia and hyperglycemia, which may enrich the etiological information and suggest future research direction on CAD.

Ablation of mitophagy receptor FUNDC1 accentuates septic cardiomyopathy through ACSL4-dependent regulation of ferroptosis and mitochondrial integrity.

Sepsis evokes compromised myocardial function prompting heart failure albeit target therapy remains dismal. Our study examined the possible role of mitophagy receptor FUNDC1 in septic cardiomyopathy. A sepsis model was established using cecal ligation and puncture (CLP) in FUNDC1 knockout (FUNDC1-/-) and WT mice prior to the evaluation of cardiac morphology, echocardiographic and cardiomyocyte contractile, oxidative stress, apoptosis, necroptosis, and ferroptosis. RNAseq analysis depicted discrepant patterns in mitophagy, oxidative stress and ferroptosis between CLP-challenged and control murine hearts. Septic patients displayed cardiac injury alongside low plasma FUNDC1 and iron levels. CLP evoked interstitial fibrosis, cardiac dysfunction (lowered ejection fraction, fractional shortening, shortening/relengthening velocity, peak shortening and electrically-stimulated intracellular Ca2+ rise, alongside increased LV end systolic diameter and relengthening duration), O2- buildup, apoptosis, necroptosis, and ferroptosis (downregulated GPX4 and SLC7A11), the responses of which were accentuated by FUNDC1 ablation. In particular, levels of lipid peroxidation enzyme acyl-CoA synthetase long-chain family member 4 (ACSL4) were upregulated following CLP procedure, with a more pronounced response in FUNDC1-/- mice. Co-immunoprecipitation and interaction interface revealed an evident interaction between FUNDC1 and ACSL4. In vitro studies revealed that the endotoxin lipopolysaccharide provoked cardiomyocyte contractile and lipid peroxidation anomalies, the responses were reversed by the mitophagy inducer oleanolic acid, inhibition of ACSL4 and ferroptosis. These findings favor a role for FUNDC1-ACSL4-ferroptosis cascade in septic cardiomyopathy.

Methylation-related differentially expressed genes as potential prognostic biomarkers for cervical cancer.

Aim: To discover novel methylation-related differentially expressed genes (MRDEGs) for cervical cancer, with a focus on their potential for early diagnosis and prognostic assessment. Materials & methods: We integrated data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. TCGA-MRDEGs were identified by analyzing differentially methylated genes (DMGs) and their correlation with gene expression. We examined GEO datasets GSE39001, GSE9750, and GSE46306 for GEO-MRDEGs. Overlapping MRDEGs were subjected to overall survival (OS) analysis to identify prognostic markers. The expression and methylation levels of these genes were validated in a total of 30 tissue samples, comprising 20 from cervical cancer patients and 10 from normal cervical tissues, using qRT-PCR and MassARRAY EpiTYPER Assay. Results: A total of 314 TCGA-MRDEGs and 40 GEO-MRDEGs were identified. Intersection analysis yielded 10 overlapping MRDEGs. Notably, NOVA1, GSTM5, TRHDE, and CXCL12 were found to have reduced expression and increased methylation in cervical cancer, which correlated with poor prognosis. The methylation status and expression levels of these genes were confirmed in tissue specimens. Conclusion: We identified four MRDEGs as potential prognostic biomarkers for cervical cancer. Their clinical utility is highlighted, but further validation in larger cohorts is required to establish their clinical significance.

PathoTracker: an online analytical metagenomic platform for Klebsiella pneumoniae feature identification and outbreak alerting.

Clinical metagenomics (CMg) Nanopore sequencing can facilitate infectious disease diagnosis. In China, sub-lineages ST11-KL64 and ST11-KL47 Carbapenem-resistant Klebsiella pneumoniae (CRKP) are widely prevalent. We propose PathoTracker, a specially compiled database and arranged method for strain feature identification in CMg samples and CRKP traceability. A database targeting high-prevalence horizontal gene transfer in CRKP strains and a ST11-only database for distinguishing two sub-lineages in China were created. To make the database user-friendly, facilitate immediate downstream strain feature identification from raw Nanopore metagenomic data, and avoid the need for phylogenetic analysis from scratch, we developed data analysis methods. The methods included pre-performed phylogenetic analysis, gene-isolate-cluster index and multilevel pan-genome database and reduced storage space by 10-fold and random-access memory by 52-fold compared with normal methods. PathoTracker can provide accurate and fast strain-level analysis for CMg data after 1 h Nanopore sequencing, allowing early warning of outbreaks. A user-friendly page ( http://PathoTracker.pku.edu.cn/ ) was developed to facilitate online analysis, including strain-level feature, species identifications and phylogenetic analyses. PathoTracker proposed in this study will aid in the downstream analysis of CMg.

Layer-by-layer fabrication of covalent organic frameworks on stainless steel needles as solid-phase microextraction probe coupled with electrospray ionization mass spectrometry for enrichment and determination of tyrosine kinase inhibitors in biosamples.

Sunitinib, N-desmethyl imatinib, dasatinib, imatinib, and bosutinib are tyrosine kinase inhibitors (TKIs) that are commonly employed in the treatment of a multitude of cancers. However, the inappropriate concentrations of TKIs can result in ineffective treatment or the emergence of multiple adverse effects. Consequently, the development of a rapid and sensitive analytical method for TKIs is of paramount importance for the safe administration of drugs. In this work, solid-phase microextraction (SPME) probe combined with an electrospray ionization mass spectrometry (ESI-MS) coupling platform was constructed for rapid and sensitive determination of TKIs. The covalent organic frameworks (COFs) coated SPME probe was made of 2,4,6-tris(4-aminophenyl)-1,3,5-triazine (TAPT) and 2,5-dibutoxyterephthalaldehyde (DBTA) by in-situ layer-by-layer chemical bonding synthesis strategy. The TAPT-DBTA-SPME probe exhibited several advantageous properties which rendered it suitable for the enrichment of TKIs. Under the optimal conditions, the developed analytical method demonstrated a broad linear range (0.05-500.00 µg/L), a low limit of detection (0.02 µg/L) and a high enrichment factor (51-203) for TKIs. The developed analytical method was successfully applied to a pharmacokinetic study of TKIs in mouse plasma and tissue matrix, demonstrating that the proposed analytical method has promise for clinical applications and metabolic monitoring.

Taste or health: The impact of packaging cues on consumer decision-making in healthy foods.

According to the theory of dietary regulation, consumers frequently encounter conflicts between healthiness and tastiness when selecting healthy foods. This study explores how packaging cue that highlight "tasty" versus "healthy" affect consumers' intentions to purchase healthy food. After an Implicit Association Test (IAT) confirmed a perceived lack of tastiness in health foods in the Preliminary study, Study 1 analyzed pricing and packaging details of the top 200 most-popular items in each of the ten healthy food categories on a major online shopping platform. Results showed that products with taste-focused cues commanded higher prices, indicating stronger consumer acceptance of healthy foods marketed as delicious. To address the causality limitations of observational studies, Study 2 used an experimental design to directly measure the impact of these cues on purchase intentions and perceptions of energy, healthiness, and tastiness. Findings revealed that taste-focused cues significantly boosted purchase intentions compared to health-focused cues, although they also diminished the perceived healthiness of the products. Moreover, in the control group exposed to unhealthy food options, health-emphasized packaging also increased purchase intentions, indicating that consumers seek a balance between healthiness and tastiness, rather than prioritizing health alone. Study 3 further explored the impact of cognitive load over these cue influences, revealing a heightened inclination among consumers to purchase healthy products with taste-focused cue under high cognitive load state. These insights have direct implications for food packaging design, suggesting that emphasizing a balance of taste and health benefits can effectively enhance consumer engagement. The study, which conducted in China, also opens avenues for future research to explore similar effects, maybe in different cultural contexts, different consumer groups, and under varied cognitive conditions.

Evaluating the Usability of mHealth Apps: An Evaluation Model Based on Task Analysis Methods and Eye Movement Data.

Advancements in information technology have facilitated the emergence of mHealth apps as crucial tools for health management and chronic disease prevention. This research work focuses on mHealth apps for the management of diabetes by patients on their own. Given that China has the highest number of diabetes patients in the world, with 141 million people and a prevalence rate of 12.8% (mentioned in the Global Overview of Diabetes), the development of a usability research methodology to assess and validate the user-friendliness of apps is necessary. This study describes a usability evaluation model that combines task analysis methods and eye movement data. A blood glucose recording application was designed to be evaluated. The evaluation was designed based on the model, and the feasibility of the model was demonstrated by comparing the usability of the blood glucose logging application before and after a prototype modification based on the improvement suggestions derived from the evaluation. Tests showed that an improvement plan based on error logs and post-task questionnaires for task analysis improves interaction usability by about 24%, in addition to an improvement plan based on eye movement data analysis for hotspot movement acceleration that improves information access usability by about 15%. The results demonstrate that this study presents a usability evaluation model for mHealth apps that enables the effective evaluation of the usability of mHealth apps.

A Novel Amino Acid-Related Gene Signature Predicts Overall Survival in Patients With Hepatocellular Carcinoma.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is an extremely harmful malignant tumor in the world. Since the energy metabolism and biosynthesis of HCC cells are closely related to amino acids, it is necessary to further explore the relationship between amino acid-related genes and the prognosis of HCC to achieve individualized treatment. We herein aimed to develop a prognostic model for HCC based on amino acid genes. METHODS: In this study, RNA-sequencing data of HCC patients were downloaded from the TCGA-LIHC cohort as the training cohort and the GSE14520 cohort as the validation cohort. Amino acid-related genes were derived from the Molecular Signatures Database. Univariate Cox and Lasso regression analysis were used to construct an amino acid-related signature (AARS). The predictive value of this risk score was evaluated by Kaplan-Meier (K-M) curve, receiver operating characteristic (ROC) curve, univariate and multivariate Cox regression analysis. Gene set variation analysis (GSVA) and immune characteristics evaluation were used to explore the underlying mechanisms. Finally, a nomogram was established to help the personalized prognosis assessment of patients with HCC. RESULTS: The AARS comprises 14 amino acid-related genes to predict overall survival (OS) in HCC patients. HCC patients were divided into AARS-high group and AARS-low group according to the AARS scores. The K-M curve, ROC curve, and univariate and multivariate Cox regression analysis verified the good prediction efficiency of the risk score. Using GSVA, we found that AARS variants were concentrated in four pathways, including cholesterol metabolism, delayed estrogen response, fatty acid metabolism, and myogenesis metabolism. CONCLUSION: Our results suggest that the AARS as a prognostic model based on amino acid-related genes is of great value in the prediction of survival of HCC, and can help improve the individualized treatment of patients with HCC.

The Difference between Plasmon Excitations in Chemically Heterogeneous Gold and Silver Atomic Clusters.

Weak doping can broaden, shift, and quench plasmon peaks in nanoparticles, but the mechanistic intricacies of the diverse responses to doping remain unclear. In this study, we used the time-dependent density functional theory (TD-DFT) to compute the excitation properties of transition-metal Pd- or Pt-doped gold and silver atomic arrays and investigate the evolution characteristics and response mechanisms of their plasmon peaks. The results demonstrated that the Pd or Pt doping of the off-centered 10 × 2 atomic arrays broadened or shifted the plasmon peaks to varying degrees. In particular, for Pd-doped 10 × 2 Au atomic arrays, the broadened plasmon peak significantly blueshifted, whereas a slight red shift was observed for Pt-doped arrays. For the 10 × 2 Ag atomic arrays, Pd doping caused almost no shift in the plasmon peak, whereas Pt doping caused a substantial red shift in the broadened plasmon peak. The analysis revealed that the diversity in these doping responses was related to the energy positions of the d electrons in the gold and silver atomic clusters and the positions of the doping atomic orbitals in the energy bands. The introduction of doping atoms altered the symmetry and gap size of the occupied and unoccupied orbitals, so multiple modes of single-particle transitions were involved in the excitation. An electron transfer analysis indicated a close correlation between excitation energy and the electron transfer of doping atoms. Finally, the differences in the symmetrically centered 11 × 2 doped atomic array were discussed using electron transfer analysis to validate the reliability of this analytical method. These findings elucidate the microscopic mechanisms of the evolution of plasmon peaks in doped atomic clusters and provide new insights into the rational control and application of plasmons in low-dimensional nanostructures.

The Configuration Identification of Guanine Molecules Adsorbed on the Si(100) Surface by Using XPS Shake-up Satellites and NEXAFS.

Bioelectronic devices can be manufactured by organic-inorganic hybrid systems based on biomolecules and silicon semiconductors. The performance of the hybrid systems is largely determined by the adsorption manners of biomolecules on the silicon surface. In this paper, we demonstrated that the X-ray photoelectron spectroscopy (XPS) shake-up satellites and near-edge X-ray absorption fine-structure (NEXAFS) spectra at the carbon K-edges can be used to distinguish the interface of guanine molecules anchored on Si(100) surface. There are only 9 possible stable guanine@Si(100) hybrid systems that have been found based on the density functional theory. According to the characteristic peaks, it is confirmed that NEXAFS spectra are more sensitive to the identification of adsorption configurations. While the first characteristic peak in the low energy region of NEXAFS spectra are capable of distinguishing chemical bonds at the interface of the adsorption configurations. These results may facilitate a better understanding of the interface formations between biomolecules and silicon surfaces, which could be further utilized for the new bioelectronic device design.

A homogeneous binary matrix assisted laser desorption/ionization time-of-flight mass spectrometry assay for determination of artificial sweeteners in beverages.

Artificial sweeteners have been widely used as additives in various beverages. Due to the safety risks associated with artificial sweeteners, it is essential to develop a simple, rapid, and high-throughput method for the analysis of artificial sweeteners. Here, we report a homogeneous binary matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) assay for the simultaneous analysis of sweeteners including aspartame (ASP), neotame (NEO), and advantame (ADV) with a simple dilution step. The combination of nanodiamonds with 2,5-dihydroxybenzoic acid effectively improved the signal response of sweeteners, decreased the background noise, and improved the "spot-to-spot" repeatability. After the optimization, the method exhibits low limits of detection (ASP: 20 nΜ; NEO: 10 nΜ; ADV: 5 nΜ), good linearity (r > 0.995), satisfactory accuracy (96.2-103.0%), and lower RSDs (1.5-5.8%). Finally, the target sweeteners in 17 soft beverages were successfully determined with this method, showing the potential for the routine analysis of artificial sweeteners.

Pectin-based cinnamon essential oil Pickering emulsion film with two-sided differential wettability: A major role in the spatial distribution of microdroplets.

Pickering emulsions have attracted much attention as a novel emulsifying technology. This research to explore Zein-Citrus pectin nanoparticles stabilized cinnamon essential oil (CEO) Pickering emulsion (ZCCPEs) for constructing Pickering emulsion edible film (PEF). Unlike traditional research, which focuses on antibacterial and antioxidant activities, our research examined the physical properties of PEF, specifically changes in wettability. The results show that PEF has better transparency and tensile strength than the pectin alone direct emulsion film (PAEF), and the spatial distribution of Pickering emulsion droplets gives different wettability on both sides of PEF. The partially hydrophobic upside has important application value in food packaging. At the same time, the PEF is biodegradable and environmentally non-polluting. The edible film loaded with essential oils, developed based on the Pickering stabilization mechanism in this study, possesses several desirable characteristics for potential used as bioactive packaging films in food applications.

The plasma viral communities associate with clinical profiles in a large-scale haematological patients cohort.

BACKGROUND: Haematological patients exhibit immune system abnormalities that make them susceptible to viral infections. Understanding the relationship between the virome in the blood plasma of haematological patients and their clinical characteristic is crucial for disease management. We aimed to explore the presence of viral pathogens and identify close associations between viral infections and various clinical features. RESULTS: A total of 21 DNA viruses and 6 RNA viruses from 12 virus families were identified from 1383 patients. Patients with haematological diseases exhibited significantly higher diversity, prevalence, and co-detection rates of viral pathogens. During fever episodes, pathogen detection was notably higher, with Epstein-Barr virus (EBV) and Mucorales infections being the most probable culprits for fever symptoms in non-haematological patients. The detection rate of torque teno virus (TTV) significantly increases in haematological patients after transplantation and during primary lung infections. Additionally, TTV-positive patients demonstrate significantly higher absolute neutrophil counts, while C-reactive protein and procalcitonin levels are notably lower. Furthermore, TTV, cytomegalovirus, and parvovirus B19 (B19V) were found to be more prevalent in non-neutropenic patients, while non-viral pathogenic infections, such as Gram-negative bacteria and Mucorales, were more common in neutropenic patients. Pegivirus C (HPgV-C) infection often occurred post-transplantation, regardless of neutropenia. Additionally, some viruses such as TTV, B19V, EBV, and HPgV-C showed preferences for age and seasonal infections. CONCLUSIONS: Analysis of the plasma virome revealed the susceptibility of haematological patients to plasma viral infections at specific disease stages, along with the occurrence of mixed infections with non-viral pathogens. Close associations were observed between the plasma virome and various clinical characteristics, as well as clinical detection parameters. Understanding plasma virome aids in auxiliary clinical diagnosis and treatment, enabling early prevention to reduce infection rates in patients and improve their quality of life. Video Abstract.

Tracking intra-species and inter-genus transmission of KPC through global plasmids mining.

Klebsiella pneumoniae carbapenemase (KPC) poses a major public health risk. Understanding its transmission dynamics requires examining the epidemiological features of related plasmids. Our study compiled 15,660 blaKPC-positive isolates globally over the past two decades. We found extensive diversity in the genetic background of KPC, with 23 Tn4401-related and 341 non-Tn4401 variants across 163 plasmid types in 14 genera. Intra-K. pneumoniae and cross-genus KPC transmission patterns varied across four distinct periods. In the initial periods, plasmids with narrow host ranges gradually established a survival advantage. In later periods, broad-host-range plasmids became crucial for cross-genera transmission. In total, 61 intra-K. pneumoniae and 66 cross-genus transmission units have been detected. Furthermore, phylogenetic reconstruction dated the origin of KPC transmission back to 1991 and revealed frequent exchanges across countries. Our research highlights the frequent and transient spread events of KPC mediated by plasmids across multiple genera and offers theoretical support for high-risk plasmid monitoring.

Psychometric properties of disease-specific health-related quality of life instruments for food allergy: A COnsensus-based Standards for the selection of health Measurement INstruments-based systematic review.

Food allergies severely impact the health-related quality of life (HRQoL) of patients and their caregivers (family or informal caregivers). Currently there is no comprehensive review to provide an overview and critical assessment of the instruments in the field. Six databases were searched from inception until 10 August 2023, and a combination of subject terms and free words was used to search the literature. We used the COnsensus-based Standards for the selection of health Measurement INstruments methodology (COSMIN) to evaluate the measurement properties of the instruments. Forty-one studies reported on ten eligible instruments. Based on COSMIN guidelines, one instrument was recommended for Grade A, and the remaining nine instruments were recommended for Grade B. The Grade A instrument identified, the Food Allergy Quality of Life Questionnaire-Parent Form (FAQLQ-PF), can help researchers assess the effectiveness of treatment for patients with food allergy and to understand the psychosocial impact of the disease on patients.

Global evolutionary dynamics of virulence genes in ST11-KL47 carbapenem-resistant Klebsiella pneumoniae.

ST11-KL47 is a hypervirulent carbapenem-resistant Klebsiella pneumoniae (CRKP) that is highly prevalent in China and poses a major public health risk. To investigate the evolutionary dynamics of virulence genes in this subclone, we analysed 78 sequenced isolates obtained from a long-term study across 29 centres from 17 cities in China. Virulence genes were located in large hybrid pNDM-Mar-like plasmids (length: ∼266 kilobases) rather than in classical pK2044-like plasmids. These hybrid plasmids, derived from the fusion of pK2044 and pNDM-Mar plasmids mediated by insertion sequence (IS) elements (such as ISKpn28 and IS26), integrated virulence gene fragments into the chromosome. Analysis of 217 sequences containing the special IncFIB (pNDM-Mar) replicon using public databases indicated that these plasmids typically contained T4SS-related and multiple antimicrobial resistance genes, were present in 24 countries, and were found in humans, animals, and the environment. Notably, the chromosomal integration of virulence genes was observed in strains across five countries across two continents. In vivo and in vitro models showed that the large hybrid plasmid increased the host fitness cost while increasing virulence. Conversely, virulence genes transferred to chromosomes resulted in increased fitness and lower virulence. In conclusion, virulence genes in the plasmids of ST11-KL47 CRKP are evolving, driven by adaptive negative selection, to enable vertical chromosomal inheritance along with conferring a survival advantage and low pathogenicity.