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Phenotypic and molecular characterization of K64 putative hypervirulent carbapenem-resistant Klebsiella pneumoniae

Objectives Although K64-type carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp) has been reported, its molecular characteristics remain unclear. This study aimed to characterize the phenotypic and molecular features of K64 putative hypervirulent CR- K. pneumoniae (phvKp).. Methods Two K64 putative hypervirulent CR- K. pneumoniae isolates were recovered from a patient in the emergency intensive care unit of a Chinese teaching hospital. Antimicrobial susceptibility testing was performed using broth microdilution method. Multilocus sequence typing (MLST) was used for molecular typing. Virulence was assessed using a mouse infection model, and whole-genome sequencing was performed to analyze resistance and virulence genes. Results Both isolates were resistant to aztreonam, cephalosporins, carbapenems, quinolones, and aminoglycosides, but susceptible to trimethoprim/sulfamethoxazole, colistin, tigecycline, and ceftazidime/avibactam. MLST identified both isolates as ST11. The mouse infection model showed elevated virulence of two clinical isolates, which was significantly higher than that of the classical non-hypervirulent reference strain ATCC 13883. Genomic analysis identified 133 virulence- and pathogen-associated genes, including those involved in fimbriae synthesis, iron acquisition, and enterobactin production. Both isolates harbored the rmpA gene, but string tests were negative. Sequence alignment revealed >80% similarity among 13 rmpA-harboring IncHI1B plasmids. Conclusions K64 ST11-type phvKp has emerged in China, exhibiting multidrug resistance and putative hypervirulence characteristics. The increase in virulence of K.pneumoniae involves multiple factors, and these factors act independently or the synergistic effect leads to elevated virulence potential.

Single-cell tracking of the fittest in AML

Decoding orbital angular momentum in turbid tissue-like scattering medium with deep learning

Abstract Structured light beams carrying orbital angular momentum (OAM), such as Laguerre–Gaussian modes, are promising tools for high-capacity optical communications and advanced biomedical imaging. However, multiple scattering in turbid media distorts their phase and amplitude, complicating the retrieval of topological charge. Using experimentally acquired three-channel intensity and interference measurements from 25 independent acquisition sessions, we evaluate signed 11-class and unsigned 6-class topological-charge classification with a matched CNN baseline, an Angular Fourier Transform CNN (AFT-CNN), and a pretrained ResNet18 baseline. The best-performing models achieve high accuracy in the low-scattering regime, with the CNN and ResNet18 remaining near 95% at $$z/l^* = 2,$$ but accuracy drops sharply around $$z/l^* \approx 4.$$ These results indicate that sign-dependent OAM information can survive multiple scattering in the low-scattering regime and can be decoded from three-channel measurements with deep learning.

Global long-term agricultural experiments reveal consequences of mineral fertilization for soil microbiomes

Severity-dependent metabolic rewiring in COVID-19 based on untargeted metabolomic profiling of patient plasma

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a major global health challenge, characterised by a heterogeneous clinical spectrum. While metabolomic studies have identified disruptions in amino acid, lipid, nucleotide, and energy metabolism during COVID-19, these investigations often lack fine-grained clinical stratification. In this study, we performed untargeted metabolomic profiling of plasma from 25 participants, including five healthy controls and twenty COVID-19 patients classified into four severity groups (COV1–COV4) based on pulmonary involvement and the need for respiratory support. Using ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS), 541 metabolites were detected and analysed across all samples. Principal component analysis revealed a progressive metabolic divergence corresponding to disease severity. Monocarboxylic acid dysregulation was predominant in early to moderate cases (COV1–COV3), whereas severe disease (COV4) demonstrated a shift toward pyrimidine metabolism enrichment, consistent with heightened nucleotide turnover driven by viral replication and immune cell proliferation. Phenylalanine metabolism emerged as a consistently enriched pathway in COV1–COV3, suggesting aromatic amino acid perturbations as early markers of metabolic stress and immune activation. In contrast, pyrimidine pathway activation in COV4 could reflect profound systemic metabolic reprogramming associated with critical illness. These findings provide novel insights into COVID-19 pathophysiology, highlighting stage-specific metabolic signatures and potential biomarkers for disease monitoring. Our results support the concept of metabolomics-guided precision medicine, offering a rationale for targeted therapeutic interventions based on disease stage and metabolic phenotype.

In search of dependencies in myeloma, consider IRF2 too

A novel glioma prognosis marker CAMK2A is related to immune microenvironment and may be involved in Ras/Raf/MEK/ERK signaling

Highly efficient anogenital transmission of clade Ia monkeypox virus associated with increased shedding

Clinical and cost-effectiveness of the digital intervention, MyWay Diabetes, in people with type 2 diabetes living in Greater Manchester during the COVID-19 pandemic

Aims We aimed to assess a) whether using the digital intervention, MyWay Diabetes (MWD), during the COVID-19 pandemic in Greater Manchester was associated with improvements in glycaemia and cardiovascular risk factors; and b) the cost-effectiveness of MWD. Methods From 01 st July 2019–30 th April 2022, we assessed risk factor changes in MWD users (n = 507) with T2D, adjusting for changes in a matched control group of non-users (n = 10,135). Economic evaluation was conducted using United Kingdom Prospective Diabetes Study Outcomes Model version 2.1 simulating 1,000 patients over 40-years based on observed risk factor changes. Results Over 2-years follow-up, MWD use was associated with a clinically significant reductions in HbA1c of 3.1 (95%CI: 1.5 to 4.6) mmol/mol and decreases in systolic blood pressure (1.4 (0.2 to 2.6) mmHg) and cholesterol (0.1 (0.02 to 0.2) mmol/L) when compared to non-users. Including medication costs, MWD generated more health (0·015 QALYs) and lower costs (−£67 per person) compared to usual care. Excluding medication costs, MWD generated QALYs at a cost of £389 each, below the NICE threshold of £20,000–30,000/QALY. Interpretation At population level, the risk factor changes associated with MWD are likely to reduce long-term diabetes-related complications risks and the intervention appears cost-effective.

CD49d governs immune synapse formation through actin rearrangements and synchronizes BCR signaling in CLL

Abstract B-cell receptor (BCR) signaling is a key determinant of chronic lymphocytic leukemia (CLL) pathophysiology. CD49d, the α4 subunit of the very late antigen 4 integrin, can be activated by BCR signals; however, its role in modulating BCR functionality remains unknown. We used knockout mouse models and primary human CLL stratified by CD49d expression to address this aspect. CD49d was required for bone marrow (BM) infiltration and shaped BM infiltration patterns and patient outcomes in human CLL. In TCL1 transplantation models, the loss of CD49d abrogated BM homing and leukemic cell positioning within splenic niches. At the cellular level, CD49d-deficient murine TCL1 transgenic cells and human CD49d-low CLL cells failed to form efficient immune synapses with antigen-presenting membranes. Transcriptome analyses identified CD49d-dependent regulation of actin-associated pathways and distinct signatures of BCR responsiveness in both human and mouse cells. Consistently, CD49d-low human CLL cells displayed aberrant actin remodeling following BCR stimulation, and a second aggressive murine CLL model reproduced the actin and engraftment defects. Kinome profiling linked impaired antigen-induced BCR responses in CD49d-deficient murine cells to altered kinase activity, and pharmacologic actin perturbation phenocopied CD49d loss. In human CD49d-low CLL cells, a desynchronization of BCR-related downstream Syk and PLCɣ2 activation was found. Mechanistically, the CD49d-BCR interplay involved their colocalization, and CD49d converged with BCR signaling on a focal adhesion kinase–actin axis. In summary, our findings establish CD49d as a key regulator of BCR functionality in CLL, linking integrins to cytoskeletal dynamics and antigen responsiveness.

Metabolite profiling and enhanced antimicrobial and nematicidal activities of zinc oxide nanoparticle-biofortified Pleurotus mushrooms

Author Correction: PTC-bearing mRNA elicits a genetic compensation response via Upf3a and COMPASS components

Catalytic Enantioselective Construction of Planar Chiral Heterocyclic [2.2]Paracyclophanes Enabled by Copper-Catalyzed Desymmetric Azide-Alkyne Cycloaddition

Expression of Concern: Evaluation of the urban industrial coupling strategy based on the global production networks theory: A case study of the smart phone industry in the Guangdong-Hong Kong-Macao Greater Bay Area

A dried platelet–derived biologic for blood-brain barrier repair and hemorrhage control after TBI in mice

Abstract Traumatic brain injury (TBI) is the leading cause of death in children and adults aged 1 to 44 years. Despite its high prevalence and devastating consequences, there are currently few effective therapies that target the acute, life-threatening complications of TBI, particularly cerebral edema and intracranial hemorrhage (ICH). The blood-brain barrier (BBB) and regulation of vascular stability after injury are emerging as critical therapeutic targets. In this study, we evaluate the therapeutic potential of a first-in-class, freeze-dried platelet (FDPlt)–derived biologic in a murine model of TBI. FDPlt transfusion significantly reduces post-TBI ICH and restores cerebral vascular perfusion. Additionally, FDPlts attenuate BBB permeability, suppress intravascular leukocytosis, and mitigate neuroinflammation, as evidenced by decreased microglial activation, astrocyte reactivity, and macrophage infiltration. Transcriptomic profiling of cortical and hippocampal tissues reveals that FDPlts downregulate gene networks associated with inflammation and fibrosis, suggesting a role for FDPlts in the modulation of postinjury repair. Mechanistically, FDPlts are enriched in angiopoietin-1 (Ang-1), a key bioactive protein that signals through the Tie2 receptor pathway, a central regulator of endothelial stability. Inhibition of Tie2 exacerbates BBB permeability after TBI, an effect attenuated by FDPlt administration, implicating Ang-1 as a key mediator of FDPlt-mediated BBB protection in TBI. The BBB plays a vital role in maintaining cerebral homeostasis, and its breakdown after TBI initiates harmful cascades of edema, inflammation, and neuronal injury. Our findings demonstrate, to our knowledge, for the first time, that a dried, platelet-derived biologic can promote vascular repair and neuroprotection in TBI.

Aortic asprosin overexpression does not ameliorate disease pathophysiology in a murine model of Marfan syndrome

Abstract Marfan syndrome (MFS) is a connective tissue disorder caused by FBN1 mutations, characterised by aortic aneurysms leading to life-threatening dissections. Asprosin is the C-terminal propeptide of fibrillin-1 that was shown to function as a glucogenic hormone with critical implications in vascular pathology. However, its role in MFS remains unknown. Here, we investigate the effect of asprosin overexpression in vascular smooth muscle cells (VSMCs) and in the Marfan mouse model mgR/mgR via endothelial-targeted transduction by adeno-associated viruses (AAVs). In both human and murine VSMCs, asprosin overexpression did not alter VCAM1 or MMP9 expression, while TNF-α-stimulated asprosin-overexpressing MOVAS cells exhibited reduced IL6 levels. In mgR/mgR mice, asprosin overexpression did not affect aortic diameter or elastin integrity. Molecular analyses revealed no significant change in inflammatory or epithelial-to-mesenchymal transition (EMT) markers at the mRNA or protein level, with VCAM1 and MMP9 remaining unchanged. Together, these findings indicate that asprosin overexpression does not ameliorate the aneurysmal phenotype in MFS.

Force-moment mechanics of wiggling in connector insertion

Clinical practice teaching system for MNS cardiac rehabilitation: Delphi consensus

Background China faces a growing demand for cardiac rehabilitation professionals that outstrips available medical resources. While nursing master's candidates represent key talent reserves, current higher education lacks standardized training frameworks for cardiac rehabilitation nursing. This study developed a competency-based clinical training system through expert consensus to address this educational gap. Methods A modified two-round Delphi process engaged 22 cardiac rehabilitation experts. Initial expert feedback informed questionnaire refinement, followed by consensus-building analysis in the second round. Results The Delphi study demonstrated high engagement (100% Round 1; 96% Round 2 response rates) and acceptable expert authority (Cr = 0.83‑0.84). Kendall’s W values ranged from 0.13 to 0.21 (p < 0.05), indicating moderate agreement among experts. The consensus process yielded a structured framework of 5 domains, 29 subdomains, and 85 competency indicators. Conclusion The teaching system is scientifically valid, targeted, and practical, providing a comprehensive framework for training master's degree candidates in cardiac rehabilitation nursing.

Anti–HPA-1a fetal-neonatal alloimmune thrombocytopenia: reframing diagnostics, pathophysiology, and management

Abstract Maternal alloantibodies directed to human platelet antigen 1a (HPA-1a) on fetal platelets can induce fetal-neonatal alloimmune thrombocytopenia (FNAIT), which causes intracranial hemorrhage in 10% to 20% of fetuses/newborns. Presentation is usually unexpected and identified by neonatal bleeding. This review synthesizes advances in diagnosis, pathophysiology, and management that reshape understanding of anti–HPA-1a–mediated FNAIT. Genomic and serologic testing, together with cell-free fetal DNA for fetal HPA typing, allow accurate identification of at-risk pregnancies. HPA-1bb women who carry DRB3∗01:01 are at greatest risk of forming clinically significant anti–HPA-1a. Not only anti–HPA-1a levels but also structural features, particularly decreased Fc fucosylation enhancing Fc gamma receptor–mediated effector functions, more accurately determine disease severity. Furthermore, increased Fc galactosylation may contribute by enhancing complement activation. Fab-mediated effects affect platelets, megakaryocytes, trophoblasts, and endothelial cells. Overall, this explains why anti–HPA-1a levels and neonatal platelet counts alone do not reliably predict bleeding, including intracranial hemorrhage. Anti–HPA-1a also induces placental inflammation, increasing risks of fetal growth restriction and long-term neurodevelopmental impairment, for example, autism. Neonatal management involves random donor and matched platelet transfusions, and IV immunoglobulin (IVIG), if needed. Antenatal IVIG, with/without prednisone administered in an affected pregnancy typically increases fetal platelet counts, with management strategies varying internationally. Blocking neonatal Fc receptor has emerged as an alternative approach to both reduce maternal anti–HPAa-1a levels and inhibit its transplacental transfer. Whether antenatal treatment reduces placental inflammation requires further study. These developments support the importance of identifying predictive biomarkers of fetal risk to guide antenatal management and of preventing affected pregnancies ideally by screening all pregnancies followed by prophylaxis.

A novel Hybrid Vision Transformer with dense attention capsule network (HVT-DACapNet) model for cotton plant disease detection