Wnt signaling is a highly conserved signaling pathway that plays a critical role in controlling embryonic and organ development, as well as cancer progression. Genome-wide sequencing and gene expression profile analyses have demonstrated that Wnt signaling is involved mainly in the processes of breast cancer proliferation and metastasis. The most recent studies have indicated that Wnt signaling is also crucial in breast cancer immune microenvironment regulation, stemness maintenance, therapeutic resistance, phenotype shaping, etc. Wnt/β-Catenin, Wnt–planar cell polarity (PCP), and Wnt–Ca²⁺signaling are three well-established Wnt signaling pathways that share overlapping components and play different roles in breast cancer progression. In this review, we summarize the main findings concerning the relationship between Wnt signaling and breast cancer and provide an overview of existing mechanisms, challenges, and potential opportunities for advancing the therapy and diagnosis of breast cancer.

Research on oxidase mimics is challenging but important. In this article, mercury(II) ion enabled citrate-capped silver nanoparticles (Cit–AgNPs) exhibit catalytic activity toward the oxidation of typical chromogenic substrate 3,3′,5,5′-tetramethylbenzidine (TMB) by dissolved oxygen under mild conditions, suggesting a new type of oxidase mimic. In addition, the oxidase-like activity of Cit–AgNPs was sensitive to the concentration of mercury(II) ions and selective towards mercury(II) ions among other metal ions. Based on this, a facile colorimetric mercury(II) ion sensor was developed. Hg²⁺ was reduced on the surface of Cit–AgNPs to form Hg–Ag alloys. The Hg–Ag alloys activated oxygen and generated superoxide anions, which oxidized TMB. This discovery indicates the potential of nanoparticles for efficient enzyme mimetics.

Carbapenem-resistant Morganella morganii (CRMM) isolates, particularly those producing Klebsiella pneumoniae carbapenemase-2 (KPC-2) or New Delhi metallo-β-lactamase-1 (NDM-1), are increasingly being recognized as causative agents of nosocomial infections. However, systematic phylogeography and genetic characterization of these isolates worldwide are still lacking. Here, through seven years of surveillance of CRMM in a tertiary hospital, we analyzed the genomic characteristics of bla _KPC-2 - or bla _NDM-1 -positive CRMM isolates. Furthermore, we conducted a global genomic epidemiological study of Morganella spp. harboring bla _KPC or bla _NDM using the NCBI database over the past decade. By combining the timeline of isolate collection with the structural analysis of the plasmids, we traced the evolution of the IncL/M plasmid, which acquired the bla _KPC-2 gene. Our findings indicate that horizontal transfer of Tn 6296 based on IS 26 is crucial for the transmission of bla _KPC in CRMM isolates. Additionally, the Tn 125 transposon appears to have played an important role in early plasmid-mediated dissemination of bla _NDM ; however, it has been surpassed in recent years by other elements, including IS 26 and IS CR . In summary, through phylogeographic analysis of Morganella spp. globally, we elucidated their spatial–temporal distribution and revealed the evolutionary characteristics of KPC- or NDM-producing CRMM isolates as the predominant "epidemic" clone. IMPORTANCE: Currently, infections attributable to carbapenem-resistant Morganella morganii (CRMM) isolates harboring bla _KPC or bla _NDM are on the rise, highlighting the increasing severity of acquired antimicrobial resistance. However, systematic phylogeographic and genetic characterization of these isolates worldwide is still lacking. In this study, we elucidated the spatial–temporal distribution and evolutionary trajectory of bla _KPC and bla _NDM genes within their core genetic environments. We emphasize the necessity of strengthening surveillance and controlling these organisms in clinical settings to prevent the generation of so-called "superbug" isolates.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by memory impairment and cognitive decline, ultimately culminating in dementia. This study aims to evaluate cerebrovascular reactivity (CVR) and functional connectivity (FC) in patients with AD and mild cognitive impairment (MCI) using resting-state functional magnetic resonance imaging (rs-fMRI), bypassing the requirement for hypercapnia. The study cohort comprised 53 AD patients, 38 MCI patients, and 39 normal control (NC) subjects. CVR is derived by extracting signals within specific frequency bands of rs-fMRI. This study compares the differences in CVR and FC among the three groups, using the brain regions with CVR differences as region of interest (ROI) for FC analysis. The correlation between CVR and FC and cognitive scale score was discussed. Compared with NC subjects, AD patients exhibited a decrease in CVR in the PCUN.L, whereas MCI patients showed an increase in CVR in the PCUN.R. With PCUN.L as ROI, FC in PCUN.R decreased in AD patients, and FC in SFGmed.R and other brain regions increased in MCI patients compared with NC subjects. The results of the correlation analysis indicate that CVR in all patients, as well as FC with the PCUN.L as the ROI to the PCUN.R and SFGmed.R, show positive correlations with MMSE and MoCA scores. These results suggest that there are significant differences between CVR and FC with CVR differential brain regions as ROI among the AD, MCI, and NC groups, which may help to explain the hemodynamic mechanism. CVR obtained with rs-fMRI may be a potential biomarker for assessing cognitive impairment.

Escherichia fergusonii, a newly recognized Enterobacterale member, has gained attention due to the bla_NDM-5 resistance gene found in animals. However, to date, no clinical isolates carrying this gene have been reported. A carbapenem-resistant clinical isolate of E. fergusonii was obtained from a tertiary hospital in Zhejiang Province, China. Antimicrobial susceptibility testing, filter mating, whole-genome sequencing (WGS), plasmid stability, and fitness analysis were performed. Global phylogenetic relationships of E. fergusonii were analyzed using publicly available databases. E. fergusonii isolate EF21023765 exhibited resistance to most antibiotics, except tigecycline, colistin, and amikacin. WGS revealed bla_NDM-5 located on an IncX3 plasmid pEF-2-NDM with a genetic environment (Tn3-IS3000-IS5-bla_NDM-5-ble_MBL-trpF-dsbD-IS26-ISKox3), closely related to the previously reported plasmid pEC463-NDM5, a carbapenem resistance plasmid identified from a blood sample of Escherichia coli collected in 2016 at the same Chinese hospital. This finding demonstrates the 5-year persistence of related IncX3 plasmids across distinct Escherichia species, specifically from E. coli to E. fergusonii. The plasmid pEF-2-NDM demonstrated a relatively stable state in the plasmid stability experiment. Growth rate analysis revealed a significant fitness cost associated with the bla_NDM-5-carrying IncX3 plasmid, as evidenced by a 6 % higher growth rate in E. coli J53 compared to the transconjugant strain J53/pEF-2-NDM (1.00 ± 0.02 vs 0.94 ± 0.02). Phylogenetic analysis revealed significant genetic diversity in E. fergusonii, predominantly found in the UK, China, and the US, with livestock and avian as the primary hosts. In addition, ST12029 was the most prevalent sequence type. To our knowledge, this is the first report of an IncX3 type plasmid carrying bla_NDM-5 from a clinical E. fergusonii isolate. Our findings not only reveal the cross-species transmission capability of E. fergusonii, but also underscore its potential as an emerging pathogen, highlighting the need for enhanced surveillance to monitor the spread of bla_NDM-5-producing isolates.

Background: Middle cerebral artery stenosis (MCA-S) impairs cerebral perfusion and vascular pulsatility, potentially disrupting cerebrospinal fluid dynamics. We evaluated perivascular diffusivity in MCA-S using diffusion tensor image analysis along the perivascular space (DTI-ALPS) index and the redirected ALPS (ro-ALPS) index, and assessed their clinical correlations. Methods: Thirty-seven patients with MCA-S and 41 matched healthy controls (HCs) underwent MRI and cognitive function testing. We compared the DTI-ALPS index and ro-ALPS indices between the two groups and performed correlation analyses with cognitive scores and clinical indicators, including high-density lipoprotein, homocysteine, and choroid plexus (CP) volume. Results: The results showed that both DTI-ALPS index and ro-ALPS index were significantly lower in the MCA-S group than in the HC group (both p < 0.001). In MCA-S patients, the DTI-ALPS index was negatively correlated with CP volume ( r = −0.541, p _FDR = 0.012), and the ro-ALPS index showed a negative correlation with CP volume ( r = −0.568, p _FDR < 0.001). Conclusion: These findings suggest that perivascular clearance is impaired in patients with MCA-S, as reflected by lower ALPS indices. These ALPS indices, as imaging biomarkers, show significant associations with CP volume, suggesting their potential utility in monitoring disease progression.