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Background The main issue of the Klebsiella pneumoniae species complex (KpSC) research in clinical settings is the accurate identification and differentiation of the closely related species within this complex. Moreover, the emergence and spread of carbapenem-resistant K. pneumoniae (CRKP) represent a significant public health threat due to limited treatment options and high mortality rates. Understanding the genetic basis of resistance and virulence is crucial for developing effective infection control strategies. In this work, the genomic epidemiology and antimicrobial resistance profile of KpSC isolates from Wenzhou, China, was investigated to fully understand the implications of the KpSC in clinical settings. Methods We conducted a comprehensive analysis of 156 clinical KpSC isolates collected from a tertiary hospital in China over a three-year period (2019–2021). Antimicrobial susceptibility testing was performed according to CLSI standards. Whole-genome sequencing (WGS) and subsequent bioinformatic analyses were conducted to identify resistance genes, plasmid types, and virulence factors. Phylogenetic relationships were determined using maximum-likelihood analysis. Results All CRKP isolates exhibited high levels of resistance to carbapenems, cephalosporins, and aminoglycosides. The most prevalent carbapenemase genes were bla KPC−2 (100%), with significant associations between bla KPC−2 and ST11. Phylogenetic analysis revealed considerable genetic diversity, with over 50 sequence types (STs) present. A subset of isolates harbored both resistance and hypervirulence genes, including rmpA , rmpA2 , and siderophore systems, which were associated with potential higher pathogenesis. Conclusion This study provides novel insights into the molecular epidemiology of KpSC in Wenzhou, China, highlighting the coexistence of antimicrobial resistance and virulence factors in clinical isolates. The findings underscore the importance of continuous genomic surveillance and targeted therapeutic strategies to combat KpSC infections. Our research fills critical gaps in the current understanding of KpSC epidemiology in China and offers valuable data for global comparative studies, contributing to the development of effective infection control measures. Genomic surveillance in China thus provides crucial insights for local risk mapping and informs necessary adaptions for implementation of control strategies.

Multimodal medical image fusion technology can assist doctors diagnose diseases accurately and efficiently. However the multi-scale decomposition based image fusion methods exhibit low contrast and energy loss. And the sparse representation based fusion methods exist weak expression ability caused by the single dictionary and the spatial inconsistency. To solve these problems, this paper proposes a novel multimodal medical image fusion method based on nonsubsampled shearlet transform (NSST) and convolutional sparse representation (CSR). First, the registered source images are decomposed into multi-scale and multi-direction sub-images, and then these sub-images are trained respectively to obtain different sub-dictionaries by the alternating direction product method. Second, different scale sub-images are encoded by the convolutional sparse representation to get the sparse coefficients of the low frequency and the high frequency, respectively. Third, the coefficients of the low frequency are fused by the regional energy and the average L1 norm. Meanwhile the coefficients of the high frequency are fused by the improved spatial frequency and the average l1 norm. Finally, the final fused image is reconstructed by inverse NSST. Experimental results on serials of multimodal brain images including CT,MR-T2,PET and SPECT demonstrate that the proposed method has the state-of-the-art performance compared with other current popular medical fusion methods whatever in objective and subjective assessment.

Background Overactivated microglia are a key contributor to Parkinson’s disease (PD) by inducing neuroinflammation. CD200R1, a membrane glycoprotein mainly found on microglia, is crucial for maintaining quiescence with its dysregulation linked to microglia’s abnormal activation. We and other groups have reported a decline in CD200R1 levels in several neurological disorders including PD. However, the mechanism regulating CD200R1 expression and the specific reasons for its reduction in PD remain largely unexplored. Given the pivotal role of transcription factors in gene expression, this study aimed to elucidate the transcriptional regulation of CD200R1 and its implications in PD. Methods The CD200R1 promoter core region was identified via luciferase assays. Potential transcription factors were predicted using the UCSC ChIP-seq database and JASPAR. NFKB1 binding to the CD200R1 core promoter was substantiated through electrophoretic mobility shift and chromatin immunoprecipitation assays. Knocking-down or overexpressing NFKB1 validated its regulatory effect on CD200R1. Correlation between decreased CD200R1 and deficient NFKB1 was studied using Genotype-Tissue Expression database. The clinical samples of the peripheral blood mononuclear cells were acquired from 44 PD patients (mean age 64.13 ± 9.78, 43.2% male, median Hoehn-Yahr stage 1.77) and 45 controls (mean age 64.70 ± 9.41, 52.1% male). NFKB1 knockout mice were utilized to study the impact of NFKB1 on CD200R1 expression and to assess their roles in PD pathophysiology. Results The study identified the CD200R1 core promoter region, located 482 to 146 bp upstream of its translation initiation site, was directly regulated by NFKB1. Significant correlation between NFKB1 and CD200R1 expression was observed in human PMBCs. Both NFKB1 and CD200R1 were significantly decreased in PD patient samples. Furthermore, NFKB1-/- mice exhibited exacerbated microglia activation and dopaminergic neuron loss after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. Conclusion Our study identified that NFKB1 served as a direct regulator of CD200R1. Reduced NFKB1 played a critical role in CD200R1 dysregulation and subsequent microglia overactivation in PD. These findings provide evidence that targeting the NFKB1-CD200R1 axis would be a novel therapeutic strategy for PD.

Background In Alzheimer’s Disease (AD), about one-third of the risk genes identified by GWAS encode proteins that function predominantly in the endocytic pathways. Among them, the Ras and Rab Interactor 3(RIN3) is a guanine nucleotide exchange factor (GEF) for the Rab5 small GTPase family and has been implicated to be a risk factor for both late onset AD (LOAD) and sporadic early onset AD (sEOAD). However, how RIN3 is linked to AD pathogenesis is currently undefined. Methods Quantitative PCR and immunoblotting were used to measure the RIN3 expression level in mouse brain tissues and cultured basal forebrain cholinergic neuron (BFCNs). Immunostaining was used to define subcellular localization of RIN3 and to visualize endosomal changes in cultured primary BFCNs and PC12 cells. Recombinant flag-tagged RIN3 protein was purified from HEK293T cells and was used to define RIN3-interactomes by mass spectrometry. RIN3-interacting partners were validated by co-immunoprecipitation, immunofluorescence and yeast two hybrid assays. Live imaging of primary neurons was used to examine axonal transport of amyloid precursor protein (APP) and β-secretase 1 (BACE1). Immunoblotting was used to detect protein expression, processing of APP and phosphorylated forms of Tau. Results We have shown that RIN3 mRNA level was significantly increased in the hippocampus and cortex of APP/PS1 mouse brain. Basal forebrain cholinergic neurons (BFCNs) cultured from E18 APP/PS1 mouse embryos also showed increased RIN3 expression accompanied by early endosome enlargement. In addition, via its proline rich domain, RIN3 recruited BIN1(bridging integrator 1) and CD2AP (CD2 associated protein), two other AD risk factors, to early endosomes. Interestingly, overexpression of RIN3 or CD2AP promoted APP cleavage to increase its carboxyl terminal fragments (CTFs) in PC12 cells. Upregulation of RIN3 or the neuronal isoform of BIN1 increased phosphorylated Tau level. Therefore, upregulation of RIN3 expression promoted accumulation of APP CTFs and increased phosphorylated Tau. These effects by RIN3 was rescued by the expression of a dominant negative Rab5 (Rab5 S34N ) construct. Our study has thus pointed to that RIN3 acts through Rab5 to impact endosomal trafficking and signaling. Conclusion RIN3 is significantly upregulated and correlated with endosomal dysfunction in APP/PS1 mouse. Through interacting with BIN1 and CD2AP, increased RIN3 expression alters axonal trafficking and procession of APP. Together with our previous studies, our current work has thus provided important insights into the role of RIN3 in regulating endosomal signaling and trafficking.

This study proposed an interpretable multi-scale infrared small object detection network (IMD-Net) design method to improve the precision of infrared small object detection and contour segmentation in complex backgrounds. To this end, a multi-scale object enhancement module was constructed, which converted artificially designed features into network structures. The network structure was used to enhance actual objects and extract shallow detail and deep semantic features of images. Next, a global object response, channel attention, and multilayer feature fusion modules were introduced, combining context and channel information and aggregated information, selected data, and decoded objects. Finally, the multiple loss constraint module was constructed, which effectively constrained the network output using multiple losses and solved the problems of high false alarms and high missed detections. Experimental results showed that the proposed network model outperformed local energy factor (LEF), self-regularized weighted sparse model (SRWS), asymmetric contextual modulation (ACM), and other state of the art methods in the intersection-over-union (IoU) and F measure values by 10.8% and 11.3%, respectively. The proposed method performed best on the currently available datasets, achieving accurate detection and effective segmentation of dim and small objects in various infrared complex background images.

the landscape of Macao shops is first architectural symbol, which has the significance of design, then landscape symbol, which has geographical significance, and also public regional symbol, which has sociological significance. No matter which kind of symbol, in the final analysis, the essence is the collection of symbolic elements, first manifested as language symbols, then is the political, economic, cultural, educational and other multi-element word-formation, and finally affect its written writing style and communication mechanism is comprehensive and pluralistic. This paper expounds the phenomenon of “argot” in the language landscape of Macao shops from the aspects of folk culture, industry linkage and resource particularity, hoping to arouse more thinking about Macao’s language landscape. It also hopes to provide some strategic thinking for changing the “single economic structure” mentioned in the outline.

Background Epidemiological studies have revealed increased Parkinson’s disease (PD) risk among individuals exposed to pesticides like 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP is frequently used to induce PD-like symptoms in research models by disrupting mitochondrial complex I (CI) function and causing dopaminergic neuronal loss in the nigrostriatal region. However, the pathway(s) through which MPTP impairs mitochondrial CI function remain to be elucidated. In this study, we aim to identify the molecular mechanisms through which MPTP modulates CI function and define the specific subunits of mitochondrial CI affected by MPTP. Methods Male mice encompassing either wild-type Sirt3 or Sirt3 K223R de-SUMOylation mutation, were intraperitoneally injected with either MPTP or saline. In vitro experiments were conducted using the SH-SY5Y cell line with or without the Sirt3 de-SUMOylation mutation. Movement performance, mitochondrial function, and protein acetylation were evaluated. Results MPTP exposure, both in vitro and in vivo, disrupted the AMPK–SENP1–Sirt3 axis, leading to impairment of mitochondrial function. Specifically, MPTP suppressed activation of AMPK, impeding the entry of SENP1 into the mitochondria. The lack of mitochondrial SENP1 resulted in increased levels of SUMOylated Sirt3, which inhibited its deacetylase activity. This led to a significant increase in the acetylation of CI subunits NDUFS3 and NDUFA5, which resulted in reduced CI activity and inhibition of mitochondrial function, and eventually dopaminergic neuronal death. In this pathway, sustained deSUMOylation mutation of Sirt3 (K223R in mice, K288R in humans) mitigated the impact of MPTP on mitochondrial dysregulation, as well as dopaminergic neuronal death and behavioral deficits. Conclusion The disordered AMPK-SENP1-Sirt3 pathway plays a crucial role in the MPTP-induced CI dysfunction and PD-like phenotype, which provide valuable insights into the mechanisms of PD pathogenesis.

Despite well documents for manganese-induced neurological deficits, limited researches are available for effects of manganese (Mn) exposure on the bone. Here we aimed to explore the associations between long-term occupational Mn exposure and bone quality among retired workers. We conducted a cross-sectional study of 304 exposed subjects ( n , male = 161 and female = 143) and 277 control retired workers ( n , male = 65 and female = 212) recruited from a ferromanganese refinery. Self-reported occupation types were used as exposure classification confirmed by expert consultation. Bone quality was measured by quantitative ultrasound (QUS). In sex-stratified analyses throughout, stiffness index (SI) and T-score levels of the participants in the highest exposed group [tertile 3 of Mn cumulative exposure index (Mn-CEI)] were significantly lower as compared with the control group among female workers (SI, mean, 61.60 vs. 68.17; T-score, mean, −3.01 vs. −2.34, both  P  < 0.05). In addition, SI and T-score were found to be negatively associated with Mn-CEI only in the highest exposure group as compared with the female controls (both P  = 0.01). However, we did not find the significant difference for SI or T-score among the male subjects in exposure models and the male controls ( P  > 0.05). Our results suggest that female retired workers in the highest Mn-exposed model (tertile 3 of Mn-CEI) potentially experience a higher risk of developing osteoporosis compared with the female controls. Further investigations on possible mechanisms on bone quality alteration are needed in the future.

Background Long-term excess exposure to environmental manganese (Mn) can lead to multi-system damage, especially in occupational populations. Therefore, we established a manganese-exposed workers healthy cohort (MEWHC), focusing on the systemic health effects related to Mn exposure. Here, we aimed to describe the follow-up activity for the MEWHC study and establish a standardized biological sample bank for the scientific management of high-quality biospecimens and the attached data from 2011 to 2017. Methods Baseline examinations for onsite workers were conducted, and the biobank for the MEWHC was first established in 2011; follow-up examinations occurred four times between July 2012 and November 2017. All questionnaires, clinical data and biological samples were routinely collected during each follow-up activity. Additional workers were recruited in 2016, which further enriched the resources of the biobank. Results A total of 2359 onsite workers and 612 retired workers at a ferromanganese refinery were enrolled in the prospective cohort, and their biological samples were obtained in the preliminary baseline survey and the follow-up investigation, including 2971 blood and urine samples from the cohort. In addition, 1524 hair samples, 1404 nail (toe and finger nails) and 1226 fecal samples were also collected. All specimens were preserved in the biobank, and the data were scientifically managed using a computer system. Conclusions The MEWHC study in China provides an effective way to obtain biological samples such as plasma, DNA, hair and urine for storage in a biobank for further study. The standardized management of various samples is crucial for accessing high-quality biospecimens.

Objective: Sepsis remains a major cause of neonatal death. To better characterize the inflammatory response during neonatal sepsis, we compared the differences in serum cytokines and chemokines between full-term neonates with sepsis and without infection. Methods: We enrolled 40 full-term neonates with sepsis and 26 full-term neonates without infection as controls between October 2016 and June 2018. Forty cytokines /chemokines in serum were analyzed using the Luminex Bead Immunoassay System. Results: Our results showed that serum IL-6, IL-8, TNF-[alpha], IL-1[beta], MIF, CXCL13, CXCL1, CXCL2, CXCL5, CXCL6, CXCL16, CCL27, CCL2, CCL8, CCL3, CCL20, CCL23, and CX3CL1 levels were significantly increased in neonates with sepsis compared to those in the control group (allp<0.05). The levels of serum CCL20, and IL-17 were higher in late-onset sepsis (LOS) than those in early-onset sepsis (EOS) (allp<0.05). Conversely, serum CXCL16 was lower in LOS than that in EOS (p<0.05). Conclusion: Our findings revealed that excessive pro-inflammatory cytokines might be involved in neonatal sepsis. In addition, chemokines significantly increased the recruitment of immune cells after infection to participate in the anti-infection defense of neonates, but this could lead to damage. Keywords: neonatal sepsis, cytokines, chemokines