Upregulation of CKS2 in immunosuppressive cells is associated with metastasis and poor prognosis in prostate cancer: a single-cell RNA-sequencing analysis.

Background: Metastasis worsens prostate cancer (PCa) prognosis, with the immunosuppressive microenvironment playing a key role in bone metastasis. This study aimed to investigate how an immunosuppressive environment promotes PCa metastasis and worsens prognosis of patients with PCa. Methods: Candidate oncogenes were identified through analysis of the Gene Expression Omnibus (GEO) database. A prognostic model was developed for the purpose of identifying target genes. A single-cell RNA sequencing data from GEO database was used to analyze the localization of target genes in the tumor microenvironment. A pan-cancer analysis was conducted to study the cancer-causing potential of target genes across different types of tumors. Results: Fifty-one genes were found to be differentially expressed in bone metastasis compared to non-metastatic PCa, with CKS2 identified as the most significant gene associated with poor prognosis. CKS2 was shown to be linked to an immunosuppressive microenvironment and osteoclastic bone metastases, as shown by its negative correlation with immune cell infiltration and osteoblast-related gene expression. Moreover, CKS2 was found in immunosuppressive cells and was linked to bone metastasis in PCa. It was also overexpressed in different types of tumors, making it as an oncogenic gene. Conclusions: This research offers a new perspective on the potential utility of CKS2 as a therapeutic target for the prevention of metastatic PCa.

Achieving rapid start-up and efficient nitrogen removal of partial-denitrification/anammox process using organic matter in brewery wastewater as carbon source.

To find a cost-efficient carbon source for the partial denitrification/anaerobic ammonium oxidation (anammox) (PD/A) process, the practicability of using the organic matter contained in brewery wastewater as carbon source was investigated. Quick self-enrichment of denitrifying bacteria was achieved by supplying brewery wastewater as organic carbon source and using the mature anammox sludge as the seeding sludge. The PD/A process was successfully established after 33-day operation and then the average total nitrogen removal efficiency reached 92.29% when the influent CODCr: NO3--N: NH4+-N ratio was around 2.5: 1.0: 0.67. The relative abundance of Thauera increased from 0.03% in the seeding sludge to 54.29% on day 110, whereas Candidatus brocadia decreased from 30.66% to 2.08%. The metagenomic analysis indicated that the sludge on day 110 contained more nar and napA (total of 41.24%) than nirK and nirS (total of 11.93%). Thus NO2--N was accumulated efficiently in the process of denitrification and sufficient NO2--N was supplied for anammox bacteria in the PD/A process. Using brewery wastewater as carbon source not only saved the cost of nitrogen removal but also converted waste into resource and reduced the treatment expense of brewery wastewater.

Proteome-wide Mendelian randomization and single-cell sequencing analysis identify the association between plasma proteins and gastric cancer.

Background: Targeted therapy is a crucial treatment modality for advanced gastric cancer, with several targets already identified, and the exploration of new targets is important. In this study, our aim was to identify plasma proteins causally associated with gastric cancer to explore novel genetic targets for the disease. Methods: Firstly, we utilized protein quantitative trait loci data for 4,907 plasma proteins and genome-wide association study data for gastric cancer to conduct Mendelian randomization (MR) analyses. This was followed by summary-data-based MR analysis on the identified plasma proteins. We then analyzed single-cell sequencing data from the Gene Expression Omnibus database to describe the distribution of genes corresponding to these proteins across different stages and cell types of gastric cancer. Results: MR analysis identified 12 plasma proteins with potential causal associations with gastric cancer, among which motilin (MLN) and THSD1 passed the summary-data-based MR test. These proteins showed no evidence of pleiotropy nor heterogeneity. In single-cell sequencing analysis, EPHB4, KDR, SEMA6B, CDH1, and C1GALT1C1 were found to be enriched in specific cell types within gastric cancer. KDR and LIFR exhibited significant differential expression between gastric cancer and normal tissues. All the 12 genes displayed differential expression across different stages of gastric cancer. Conclusions: Overall, our study identified several plasma proteins with potential causal relationships to gastric cancer. This provides potential candidate targets for gastric cancer research and advances our understanding of the disease's genetic foundations.

Single-cell analysis via manifold fitting: A framework for RNA clustering and beyond.

Single-cell RNA sequencing (scRNA-seq) data, susceptible to noise arising from biological variability and technical errors, can distort gene expression analysis and impact cell similarity assessments, particularly in heterogeneous populations. Current methods, including deep learning approaches, often struggle to accurately characterize cell relationships due to this inherent noise. To address these challenges, we introduce scAMF (Single-cell Analysis via Manifold Fitting), a framework designed to enhance clustering accuracy and data visualization in scRNA-seq studies. At the heart of scAMF lies the manifold fitting module, which effectively denoises scRNA-seq data by unfolding their distribution in the ambient space. This unfolding aligns the gene expression vector of each cell more closely with its underlying structure, bringing it spatially closer to other cells of the same cell type. To comprehensively assess the impact of scAMF, we compile a collection of 25 publicly available scRNA-seq datasets spanning various sequencing platforms, species, and organ types, forming an extensive RNA data bank. In our comparative studies, benchmarking scAMF against existing scRNA-seq analysis algorithms in this data bank, we consistently observe that scAMF outperforms in terms of clustering efficiency and data visualization clarity. Further experimental analysis reveals that this enhanced performance stems from scAMF's ability to improve the spatial distribution of the data and capture class-consistent neighborhoods. These findings underscore the promising application potential of manifold fitting as a tool in scRNA-seq analysis, signaling a significant enhancement in the precision and reliability of data interpretation in this critical field of study.

Novel RAI1:c.2736delC Variant in Smith-Magenis Syndrome: Identification by Whole Genome Sequencing and Joint Analysis.

Smith-Magenis syndrome is a complex neurobehavioral genetic disorder with a broad phenotypic spectrum. While the etiology of SMS is commonly attributed to one-copy interstitial deletion in the 17p11.2 region (90-95% of cases), variants identified by sequence analysis in RAI1 have also been reported in 5-10% of cases. In this study, we report a 9-year-old male with global cognitive and psychomotor developmental delay, musculoskeletal and cardiovascular abnormalities, and dysmorphic craniofacial features. Joint analysis was performed on the whole-genome sequencing data obtained from the proband, unaffected parents, and unaffected brother. This quad analysis identified the novel de novo RAI1:c.2736delC variant. This is the first report of this variant in the literature. This report highlights the details of genome analysis and the patient's phenotypic spectrum.

Loss of p53 and SMAD4 induces adenosquamous subtype pancreatic cancer in the absence of an oncogenic KRAS mutation.

Pancreatic cancer is associated with an oncogenic KRAS mutation in approximately 90% of cases. However, a non-negligible proportion of pancreatic cancer cases harbor wild-type KRAS (KRAS-WT). This study establishes genetically engineered mouse models that develop spontaneous pancreatic cancer in the context of KRAS-WT. The Trp53loxP/loxP;Smad4loxP/loxP;Pdx1-Cre (PPSSC) mouse model harbors KRAS-WT and loss of Trp53/Smad4. The Trp53loxP/loxP;Tgfbr2loxP/loxP;Pdx1-Cre (PPTTC) mouse model harbors KRAS-WT and loss of Trp53/Tgfbr2. We identify that either Trp53/Smad4 loss or Trp53/Tgfbr2 loss can induce spontaneous pancreatic tumor formation in the absence of an oncogenic KRAS mutation. The Trp53/Smad4 loss and Trp53/Tgfbr2 loss mouse models exhibit distinct pancreatic tumor histological features, as compared to oncogenic KRAS-driven mouse models. Furthermore, KRAS-WT pancreatic tumors with Trp53/Smad4 loss reveal unique histological features of pancreatic adenosquamous carcinoma (PASC). Single-cell RNA sequencing (scRNA-seq) analysis reveals the distinct tumor immune microenvironment landscape of KRAS-WT (PPSSC) pancreatic tumors as compared with that of oncogenic KRAS-driven pancreatic tumors.

Multi-omics and Single Cell Sequencing Analyses Reveal Associations of Mitophagy-Related Genes Predicting Clinical Prognosis and Immune Infiltration Characteristics in Osteosarcoma.

Despite recent advances in clinical treatments, identifying high-risk osteosarcoma (OS) patients remains an unresolved clinical challenge. Mitophagy, a specialized form of cellular autophagy, selectively reduces the number of mitochondria or repairs their abnormal functions in response to external stress, thereby ensuring mitochondrial quality and maintaining mitochondrial function. Mitophagy plays a crucial role in cancer development, including processes such as mitochondrial repair, homeostasis maintenance, and tumor metabolism. However, its impact on OS has not yet been reported. In this study, we collected 58 mitophagy-related genes (MPRGs) from the TARGET and GEO databases and bioinformatically screened for those associated with OS prognosis. By LASSO-multivariable Cox regression algorithm, we subsequently developed a novel scoring system, the MPRG score, and validated its significance in predicting OS prognosis. Immune landscape analysis showed patients in the low MPRG group had a higher immune infiltration level than those in the high MPRG group. Drug sensitivity differences highlighted the potential need for alternative therapeutic strategies based on MPRG scoring system. The distribution characteristics of the MPRG signature in different cell subtypes of OS were explored by single-cell sequencing analyses. In vitro experiments further confirmed the abnormal expression of screened targets in OS. Our findings highlight the role of mitophagy in OS and its potential as a therapeutic target.

Framework nucleic Acid-MicroRNA mediated hepatic differentiation and functional hepatic spheroid development for treating acute liver failure.

The specific induction of hepatic differentiation presents a significant challenge in developing alternative liver cell sources and viable strategies for clinical therapy of acute liver failure (ALF). The past decade has witnessed the blossom of microRNAs in regenerative medicine. Herein, microRNA 122-functionalized tetrahedral framework nucleic acid (FNA-miR-122) has emerged as an unprecedented and potential platform for directing the hepatic differentiation of adipose-derived mesenchymal stem cells (ADMSCs), which offers a straightforward and cost-effective method for generating functional hepatocyte-like cells (FNA-miR-122-iHep). Additionally, we have successfully established a liver organoid synthesis strategy by optimizing the co-culture of FNA-miR-122-iHep with endothelial cells (HUVECs), resulting in functional Hep:HUE-liver spheroids. Transcriptome analysis not only uncovered the potential molecular mechanisms through which miR-122 influences hepatic differentiation in ADMSCs, but also clarified that Hep:HUE-liver spheroids could further facilitate hepatocyte maturation and improved tissue-specific functions, which may provide new hints to be used to develop a hepatic organoid platform. Notably, compared to transplanted ADMSCs and Hep-liver spheroid, respectively, both FNA-miR-122-iHep-based single cell therapy and Hep:HUE-liver spheroid-based therapy showed high efficacy in treating ALF in vivo. Collectively, this research establishes a robust system using microRNA to induce ADMSCs into functional hepatocyte-like cells and to generate hepatic organoids in vitro, promising a highly efficient therapeutic approach for ALF.

VICTOR: Validation and inspection of cell type annotation through optimal regression.

Single-cell RNA sequencing provides unprecedent opportunities to explore the heterogeneity and dynamics inherent in cellular biology. An essential step in the data analysis involves the automatic annotation of cells. Despite development of numerous tools for automated cell annotation, assessing the reliability of predicted annotations remains challenging, particularly for rare and unknown cell types. Here, we introduce VICTOR: Validation and inspection of cell type annotation through optimal regression. VICTOR aims to gauge the confidence of cell annotations by an elastic-net regularized regression with optimal thresholds. We demonstrated that VICTOR performed well in identifying inaccurate annotations, surpassing existing methods in diagnostic ability across various single-cell datasets, including within-platform, cross-platform, cross-studies, and cross-omics settings.

Temporal variation in the oral microbiome and the prediction of early childhood caries in different ethnicities.

Globally, early childhood caries (ECC) is a significant public health concern, necessitating effective prediction and prevention strategies. This study aimed to explore variations in the oral microbiome of saliva from pre-school Han and Uyghur children during ECC development and establish a predictive model based on temporal oral microbiome changes. Saliva samples were collected from a single kindergarten every three months over six months. Forty-four pre-school children provided 132 samples, categorized into six groups: (1) HEF (healthy pre-school Han children), (2) HEO (Han children with caries), (3) HEP (Han children with progressive caries), (4) WEF (healthy pre-school Uyghur children), (5) WEO (Uyghur children with caries), and (6) WEP (Uyghur children with progressive caries). Illumina Miseq sequencing identified oral microbiome differences between groups and time points. The Random Forest (RF) algorithm established ECC prediction models. The T1HEO group exhibited significantly higher Chaol index, observed species index, PD whole tree index, and Shannon index than the T2HEO group (p < 0.01). Similarly, the T1WEO group had significantly higher Chaol index, observed species index, and PD whole tree index than the T2WEO group (p < 0.05). The AUROC value for the ECC prediction model based on temporal oral flora changes was 0.517 (95% CI: 0.275-0.759) for pre-school Han children and 0.896 (95% CI: 0.78-1.00) for pre-school Uyghur children. In the onset of caries in pre-school Han children, bacterial species richness and community diversity in saliva declined, paralleled by a decrease in bacterial species richness in pre-school Uyghur children's oral saliva. The ECC prediction model grounded on temporal oral microflora changes exhibited robust predictive power, particularly for pre-school Uyghur children, potentially leading to more effective ECC prevention measures.

Single-cell sequencing analysis and bulk-seq identify IGFBP6 and TNFAIP6 as novel differential diagnosis markers for postburn pathological scarring.

BACKGROUND: If not accurately diagnosed and treated, postburn pathological scars, such as keloids and hypertrophic scars, can lead to negative clinical outcomes. However, differential diagnosis at the molecular level for postburn pathological scars remains limited. Using single-cell sequencing analysis, we investigated the genetic nuances of pathological scars at the cellular level. This study aimed to identify molecular diagnostic biomarkers to distinguish between postburn keloids and hypertrophic scars. METHODS: Single-cell sequencing, differential expression, and weighted co-expression network analyses were performed to identify potential key genes for discriminating between keloids and hypertrophic scars. Postburn clinical samples were collected from our centre to validate the expression levels of the identified key genes. RESULTS: Single-cell sequencing analysis unveiled 29 and 30 cell clusters in keloids and hypertrophic scars, respectively, predominantly composed of fibroblasts. Bulk differential gene analysis showed 96 highly expressed genes and 69 lowly expressed genes in keloids compared to hypertrophic scars. By incorporating previous research, Gene Set Enrichment Analysis was conducted to select fibroblasts as the focus of research. According to the single-cell data, 301 genes were stably expressed in fibroblasts from both types of pathological scars. Consistently, Weighted Gene Co-expression Network Analysis revealed that the blue module genes were mostly hub genes associated with fibroblasts. After intersecting fibroblast-related genes in single-cell data, Weighted Gene Co-expression Network Analysis-hub module genes, and bulk differential expression genes, insulin-like growth factor binding protein 6 and tumour necrosis factor alpha-induced protein 6 were identified as key genes to distinguish keloids from hypertrophic scars, resulting in diagnostic accuracies of 1.0 and 0.75, respectively. Immunohistochemical Staining and Quantitative Reverse Transcription PCR revealed that the expression levels of tumour necrosis factor alpha induced protein 6 and insulin-like growth factor binding protein 6 were significantly lower in postburn keloids than in hypertrophic scars- CONCLUSIONS: Tumour necrosis factor alpha induced protein 6 and insulin-like growth factor binding protein 6, exhibiting high diagnostic accuracy, provide valuable guidance for the differential diagnosis and treatment of postburn pathological scars.

Whole exome sequencing in relapsed or refractory childhood cancer: case series.

Background: The prognosis for relapsed or refractory childhood cancer is approximately 20%. Genetic alterations are one of the significant contributing factors to the prognosis of patients. Objective: To investigate the molecular profile of relapsed or refractory childhood cancers in Thai cases. Methods: The study design is a descriptive study of patients <18 years old, suspected or diagnosed of relapsed or refractory childhood cancer who underwent whole exome sequencing (WES). Results: WES was successfully performed in both the tumor and the blood or saliva samples obtained from 4 unrelated patients. Six different variants were identified in the NCOR2, COL6A3, TP53, and SMAD4 genes. These alterations were found to be associated with tumor aggressiveness. Conclusion: This study is the first one to demonstrate genetic alterations by using WES in relapsed or refractory childhood cancer in Thai cases.

Decellularized Antler Cancellous Bone Matrix Material Can Serve as Potential Bone Tissue Scaffold.

Due to the limited supply of autologous bone grafts, there is a need to develop more bone matrix materials to repair bone defects. Xenograft bone is expected to be used for clinical treatment due to its exact structural similarity to natural bone and its high biocompatibility. In this study, decellularized antler cancellous bone matrix (DACB) was first prepared, and then the extent of decellularization of DACB was verified by histological staining, which demonstrated that it retained the extracellular matrix (ECM). The bioactivity of DACB was assessed using C3H10T1/2 cells, revealing that DACB enhanced cell proliferation and facilitated cell adhesion and osteogenic differentiation. When evaluated by implanting DACB into nude mice, there were no signs of necrosis or inflammation in the epidermal tissues. The bone repair effect of DACB was verified in vivo using sika deer during the antler growth period as an animal model, and the molecular mechanisms of bone repair were further evaluated by transcriptomic analysis of the regenerated tissues. Our findings suggest that the low immunogenicity of DACB enhances the production of bone extracellular matrix components, leading to effective osseointegration between bone and DACB. This study provides a new reference for solving bone defects.

Single-Cell RNA-Seq Analysis of Hearts in Patients with Fetal Tetralogy of Fallot.

INTRODUCTION: To explore the cytological characteristics of tetralogy of Fallot (TOF), we collected samples and investigated the differences in the cytological classification between normal fetal hearts and fetal hearts with congenital defects. We then performed single-cell sequencing analysis to search for possible differential genes of disease markers. METHODS: Here, the right ventricles of a heart sample with TOF and a healthy human fetal heart sample were analyzed through single-cell sequencing. Data quality control filtering, comparison, quantification, and identification of recovered cells on the raw data were performed using Cell Ranger, thereby ultimately obtaining gene expression matrices for each cell. Subsequently, Seurat was used for cell filtration, standardization, cell subgroup classification, differential expression gene analysis of each subgroup, and marker gene screening. RESULTS: Bioinformatic analysis identified 9,979 and 15,224 cells from the healthy and diseased samples, respectively, with an average read depth of 25,000/cell. The cardiomyocyte cell populations, derived from the abnormal samples identified through the first-level graph-based analysis, were separated into six distinct cell clusters. CONCLUSION: Our study provides some information on TOF in a fetus, which can offer a new reference for the early detection and treatment of TOF by comparing defective heart cells with normal heart cells.

Multiregional dynamic contrast-enhanced MRI-based integrated system for predicting pathological complete response of axillary lymph node to neoadjuvant chemotherapy in breast cancer: multicentre study.

BACKGROUND: The accurate evaluation of axillary lymph node (ALN) response to neoadjuvant chemotherapy (NAC) in breast cancer holds great value. This study aimed to develop an artificial intelligence system utilising multiregional dynamic contrast-enhanced MRI (DCE-MRI) and clinicopathological characteristics to predict axillary pathological complete response (pCR) after NAC in breast cancer. METHODS: This study included retrospective and prospective datasets from six medical centres in China between May 2018 and December 2023. A fully automated integrated system based on deep learning (FAIS-DL) was built to perform tumour and ALN segmentation and axillary pCR prediction sequentially. The predictive performance of FAIS-DL was assessed using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. RNA sequencing analysis were conducted on 45 patients to explore the biological basis of FAIS-DL. FINDINGS: 1145 patients (mean age, 50 years ±10 [SD]) were evaluated. Among these patients, 506 were in the training and validation sets (axillary pCR rate of 40.3%), 127 in the internal test set (axillary pCR rate of 37.8%), 414 in the pooled external test set (axillary pCR rate of 48.8%), and 98 in the prospective test set (axillary pCR rate of 43.9%). For predicting axillary pCR, FAIS-DL achieved AUCs of 0.95, 0.93, and 0.94 in the internal test set, pooled external test set, and prospective test set, respectively, which were also significantly higher than those of the clinical model and deep learning models based on single-regional DCE-MRI (all P < 0.05, DeLong test). In the pooled external and prospective test sets, the FAIS-DL decreased the unnecessary axillary lymph node dissection rate from 47.9% to 6.8%, and increased the benefit rate from 52.2% to 86.5%. RNA sequencing analysis revealed that high FAIS-DL scores were associated with the upregulation of immune-mediated genes and pathways. INTERPRETATION: FAIS-DL has demonstrated satisfactory performance in predicting axillary pCR, which may guide the formulation of personalised treatment regimens for patients with breast cancer in clinical practice. FUNDING: This study was supported by the National Natural Science Foundation of China (82371933), National Natural Science Foundation of Shandong Province of China (ZR2021MH120), Mount Taishan Scholars and Young Experts Program (tsqn202211378), Key Projects of China Medicine Education Association (2022KTM030), China Postdoctoral Science Foundation (314730), and Beijing Postdoctoral Research Foundation (2023-zz-012).

Integrative Analyses Reveal the Correlation Between the Airway Microbiome and Host Metabolism in Severe Community-acquired Pneumonia.

Community-acquired pneumonia (CAP) is a significant global health concern, responsible for high mortality and morbidity. Recent research has revealed a potential link between disordered microbiome and metabolism in pneumonia, although the precise relationship between these factors and severe CAP remains unclear. To address this knowledge gap, we conducted a comprehensive analysis utilizing 16S sequencing and LC-MS/MS metabolomics data to characterize the microbial profile in sputum and metabolic profile in serum in patients with severe community-acquired pneumonia (sCAP). Our analysis identified 13 genera through LEfSe analysis and 15 metabolites meeting specific criteria (P < 0.05, VIP ≥ 2, and |Log2(FC)| ≥ 2). The findings of this study demonstrate the presence of altered coordination between the microbiome of the lower respiratory tract and host metabolism in patients with sCAP. The observed concentration trends of specific metabolites across different disease stages further support the potential involvement of the serum metabolism in the development of sCAP. These correlations between the airway microbiome and host metabolism in sCAP patients have important implications for optimizing early diagnosis and developing individualized therapeutic strategies.

miRNA Sequencing Analysis in Maize Roots Treated with Neutral and Alkaline Salts.

Soil salinization/alkalization is a complex environmental factor that includes not only neutral salt NaCl but also other components like Na2CO3. miRNAs, as small molecules that regulate gene expression post-transcriptionally, are involved in plant responses to abiotic stress. In this study, maize seedling roots were treated for 5 h with 100 mM NaCl, 50 mM Na2CO3, and H2O, respectively. Sequencing analysis of differentially expressed miRNAs under these conditions revealed that the Na2CO3 treatment group had the most differentially expressed miRNAs. Cluster analysis indicated their main involvement in the regulation of ion transport, binding, metabolism, and phenylpropanoid and flavonoid biosynthesis pathways. The unique differentially expressed miRNAs in the NaCl treatment group were related to the sulfur metabolism pathway. This indicates a significant difference in the response patterns of maize to different treatment groups. This study provides theoretical evidence and genetic resources for further analysis of the molecular mechanisms behind maize's salt-alkali tolerance.

Mobile genetic element-driven genomic changes in a community-associated methicillin-resistant Staphylococcus aureus clone during its transmission in a regional community outbreak in Japan.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are now a public health concern in both community and healthcare settings worldwide. We previously identified a suspected case of a maternity clinic-centred outbreak of CA-MRSA skin infection in a regional community in Japan by PFGE-based analysis. In this study, we performed genome sequence-based analyses of 151 CA-MRSA isolates, which included not only outbreak-related isolates that we previously defined based on identical or similar PFGE patterns but also other isolates obtained during the same period in the same region. Our analysis accurately defined 133 isolates as outbreak-related isolates, collectively called the TDC clone. They belonged to a CA-MRSA lineage in clonal complex (CC) 30, known as the South West Pacific (SWP) clone. A high-resolution phylogenetic analysis of these isolates combined with their epidemiological data revealed that the TDC clone was already present and circulating in the region before the outbreak was recognized, and only the isolates belonging to two sublineages (named SL4 and SL5) were directly involved in the outbreak. Long persistence in patients/carriers and frequent intrahousehold transmission of the TDC clone were also revealed by this analysis. Moreover, by systematic analyses of the genome changes that occurred in this CA-MRSA clone during transmission in the community, we revealed that most variations were associated with mobile genetic elements (MGEs). Variant PFGE types were generated by alterations of prophages and genomic islands or insertion sequence (IS)-mediated insertion of a plasmid or a sequence of unknown origin. Dynamic changes in plasmid content, which were linked to changes in antimicrobial resistance profiles in specific isolates, were generated by frequent gain and loss of plasmids, most of which were self-transmissible or mobilizable. The introduction of IS256 by a plasmid (named pTDC02) into sublineage SL5 led to SL5-specific amplification of IS256, and amplified IS256 copies were involved in some of the structural changes of chromosomes and plasmids and generated variations in the repertoire of virulence-related genes in limited isolates. These data revealed how CA-MRSA genomes change during transmission in the community and how MGEs are involved in this process.

Chitosan-modified molybdenum selenide mediated efficient killing of Helicobacter pylori and treatment of gastric cancer.

Helicobacter pylori (H. pylori) is one of the major causes of gastrointestinal diseases, including gastric cancer. However, the acidic environment of the stomach and H. pylori resistance severely impair the antimicrobial efficacy of oral drugs. Here, a biocompatible chitosan-modified molybdenum selenide (MoSe2@CS) was designed for the simultaneous photothermal treatment of H. pylori infection and gastric cancer. MoSe2@CS showed a photothermal conversion efficiency was as high as 45.7 %. In the H. pylori-infected mice model, MoSe2@CS displayed a high bacteriostasis ratio of 99.9 % upon near-infrared irradiation. The antimicrobial functionality was also proved by transcriptomic sequencing study, which showed that MoSe2@CS combined with NIR laser irradiation modulated the gene expression of a variety of H. pylori bioprocesses, including cell proliferation and inflammation-related pathways. Further gut flora analysis results indicated that MoSe2@CS mediated PTT of H. pylori did not affect the homeostasis of gut flora, which highlights its advantages over traditional antibiotic therapy. In addition, MoSe2@CS exhibited a good photothermal ablation effect and significantly inhibited gastric tumor growth in vitro and in vivo. The comprehensive application of MoSe2@CS in the PTT of H. pylori infection and gastric cancer provides a new avenue for the clinical treatment of H. pylori infection and related diseases.

Molecular detection of Usutu virus in pools of Culex pipiens mosquitoes in Greece.

Usutu virus (USUV) is a mosquito-borne flavivirus originating from Africa, that belongs to the Japanese encephalitis virus (JEV) complex. In nature, USUV involves Culex spp. mosquitoes acting as vectors and birds as amplifying hosts. The virus has recently spread in Europe and is considered an emerging human pathogen. This is the first research study performed in Greece revealing the presence and circulation of USUV in Culex spp. mosquito populations. Out of the 1,500 mosquito pools tested with real-time RT-PCR, four (Roesch et al., 2019) were positive for USUV. All four pools were collected from the region of Central Macedonia, Northern Greece.