Gilvimarinus gilvus sp. nov. and Gilvimarinus algae sp. nov., isolated from kelp seedlings.

Two novel rod-shaped, strictly aerobic, non-motile and Gram-stain-negative bacterial strains, designated SDUM040013T and SDUM040014T, were isolated from kelp seedlings in Weihai, PR China. Cells of strain SDUM040013T were 0.3-0.4 µm wide and 0.8-1.8 µm long, catalase-positive and oxidase-positive. Growth of SDUM040013T was observed at 0-37 °C (optimum, 28-30 °C) and pH 5.5-9 (optimum, pH 8.0) and in the presence of 1-8 % (w/v) NaCl (optimum, 2 %). The DNA G+C content of strain SDUM040013T was 50.5 %. Strain SDUM040013T showed the highest 16S rRNA gene sequence similarity (97.1 %) to Gilvimarinus chinensis. Cells of strain SDUM040014T were 0.4-0.5 µm wide and 1.0-1.4 µm long, catalase-positive and oxidase-positive. Growth of SDUM040014T was observed at 4-40 °C (optimum, 28-30 °C) and pH 5.5-9 (optimum, pH 8.5) and in the presence of 0-8 % (w/v) NaCl (optimum, 2 %). The DNA G+C content of strain SDUM040014T was 56.5 %. Strain SDUM040014T showed the highest 16S rRNA gene sequence similarity (96.2%) to Gilvimarinus polysaccharolyticus. The isoprenoid quinone of both strains was Q-8 and the predominant fatty acids were summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c), summed feature 8 (C18 : 1 ω7c) and C16 : 0. Diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine were the major polar lipids. Given these phenotypic and chemotaxonomic properties, as well as phylogenetic data, strains SDUM040013T and SDUM040014T were considered to represent two novel species of the genus Gilvimarinus, for which the names Gilvimarinus gilvus sp. nov. and Gilvimarinus algae sp. nov. are proposed. The type strains are SDUM040013T (=KCTC 8123T=MCCC 1H01413T) and SDUM040014T (=KCTC 8124T=MCCC 1H01414T), respectively.

Diet-related diseases mediate the effect of masticatory function on premature death in older adults.

AIM: Although poor oral health has been a potentially modifiable risk for mortality, the precise association between functional tooth units (FTUs) and premature death as well as the underlying mechanisms remains unclear. METHODS: This study used data from the National Health and Nutrition Examination Survey (NHANES) 2009-2018. Mortality details were obtained from the National Death Index (NDI). The number of FTUs was defined as pairs of opposing natural and artificial teeth in the premolar and molar area. Weighted logistic regression models were employed to assess the relationship between FTU and premature death. Demographic characteristics, lifestyle habits, and disease histories were adjusted as confounding factors. The propensity score matching (PSM) was conducted to further assess the association between FTU and premature death. Mediation analyses were conducted to assess the role of diet-related diseases in the association between FTU and premature death. RESULTS: The analysis included 4169 individuals aged between 60 and 74 years. Participants with 0 ≤ FTUs ≤ 3 had a significantly higher odds of premature death compared to the 10 ≤ FTUs ≤ 12 group (OR = 2.142, 95% CI 1.091-4.208). After missing data imputation, 0 ≤ FTUs ≤ 3 was still significantly associated with increased odds of premature death (OR = 2.115, 95% CI 1.125-3.975). The relationship between 0 ≤ FTUs ≤ 3 and reference group persisted (OR = 2.196, 95% CI 1.296-3.721) after PSM analyses. For mechanism, mediation analysis showed that diet-related diseases, including diabetes and hypertension, partially mediated the association between FTU and premature death with proportions of 5.089% and 8.437%, respectively. CONCLUSION: The findings revealed a link between impairment of masticatory function and a heightened odds of premature death among older adults. Notably, 0 ≤ FTUs ≤ 3 is significantly correlated to premature death among this demographic, with diabetes and hypertension partially mediating the effect of FTU on premature death. Further longitudinal studies are required to validate the findings.

Association between masticatory function and depression in older adults: Results from NHANES 2009 to 2018.

AIM: Depression is prevalent among older adults. Although the number of missing teeth is considered to be associated with depression, the relationship between masticatory function, which is usually indicated by functional tooth units (FTUs), and depression in older adults remains unclear. MATERIALS AND METHODS: This study used data from the National Health and Nutrition Examination Survey (NHANES) 2009-2018. The number of FTUs was defined as pairs of opposing natural and artificial teeth. Depression was accessed using the Patient Health Questionnaire (PHQ-9), and participants who scored ≥10 on PHQ-9 were diagnosed with depression. Logistic regression analyses, propensity score matching (PSM) analyses and subgroup analyses were conducted to assess the association between FTU and depression. RESULTS: The analysis included 5764 individuals over 60 years. An association between FTU and the risk of depression among older adults was detected (odds ratio [OR] = 0.951, 95% confidence interval [CI] 0.915-0.989), suggesting protective roles of more FTUs. Significant increase in the risk of depression in 0 ≤ FTUs ≤ 3 was observed compared with 10 ≤ FTUs ≤ 12 (OR = 1.819, 95% CI 1.157-2.858). However, no significant increase in the risk of depression in 4 ≤ FTUs ≤ 9 was found. After PSM, significant increase in the risk of depression in 0 ≤ FTUs ≤ 3 was still detected compared with 4 ≤ FTUs ≤ 12 (OR = 1.484, 95% CI 1.030-2.136). Subgroup analyses demonstrated consistent results in all subgroups, except for individuals aged 76-80 and drinking regularly. CONCLUSIONS: The findings suggested the association between impaired masticatory function and the risk of depression among older adults. Longitudinal studies are needed to elucidate the role of masticatory function impairment in the development of depression further.

Case report: BTK inhibitors is effective in type II mixed cryoglobulinemia with wild-type MyD88.

This study presents two cases of type II mixed cryoglobulinemia. One case is essential, while the other is presumably associated with hepatitis B virus (HBV) infection. Both patients tested positive for monoclonal IgMκ, but negative for MyD88 mutation. They showed resistance to rituximab combined with a glucosteroid regimen, but responded positively to BTK inhibitors. These cases highlight the remarkable effectiveness of BTK inhibitors in treating refractory type II cryoglobulinemia without MyD88 mutation. The first patient achieved rapid complete remission of nephrotic syndrome within one month of starting ibrutinib, along with a significant reduction in cryoglobulin levels and abnormal clonal cells. The second patient had a rapid disappearance of rash within three days and accelerated wound healing within one week of initiating orelabrutinib, accompanied by a reduction in C-reactive protein. However, there was no reduction in cryoglobulin levels during the 12-month follow-up. These findings suggest varied mechanisms of action of BTK inhibitors in type II cryoglobulinemia through different mechanisms.

Impact of periodontitis on type 2 diabetes: a bioinformatic analysis.

BACKGROUND: Periodontitis is strongly associated with type 2 diabetes (T2D) that results in serious complications and mortality. However, the pathogenic role of periodontitis in the development of T2D and the underlain mechanism have not been fully elucidated. METHODS: A Mendelian randomization (MR) was performed to estimate the causality between two diseases. Bioinformatics tools, including gene ontology and pathway enrichment analyses, were employed to analyze the common differentially expressed genes (DEGs) in periodontitis and T2D. MR and colocalization analyses were then utilized to investigate the causal associations between potential pathogenic gene expression and the risk of T2D. Single cell-type expression analysis was further performed to detect the cellular localization of these genes. RESULTS: Genetically predicted periodontitis was associated with a higher risk of T2D (OR, 1.469; 95% CI, 1.117-1.930; P = 0.006) and insulin resistance (OR 1.034; 95%CI 1.001-1.068; P = 0.041). 79 common DEGs associated with periodontitis and T2D were then identified and demonstrated enrichment mainly in CXC receptor chemokine receptor binding and interleutin-17 signaling pathway. The integration of GWAS with the expression quantitative trait locis of these genes from the peripheral blood genetically prioritized 6 candidate genes, including 2 risk genes (RAP2A, MCUR1) and 4 protective genes (WNK1, NFIX, FOS, PANX1) in periodontitis-related T2D. Enriched in natural killer cells, RAP2A (OR 4.909; 95% CI 1.849-13.039; P = 0.001) demonstrated high risk influence on T2D, and exhibited strong genetic evidence of colocalization (coloc.abf-PPH4 = 0.632). CONCLUSIONS: This study used a multi-omics integration method to explore causality between periodontitis and T2D, and revealed molecular mechanisms using bioinformatics tools. Periodontitis was associated with a higher risk of T2D. MCUR1, RAP2A, FOS, PANX1, NFIX and WNK1 may play important roles in the pathogenesis of periodontitis-related T2D, shedding light on the development of potential drug targets.

Prevalence of unhealthy behaviors and their associations with non-suicidal self-injury, suicidal ideation and suicide attempt among Chinese adolescents.

BACKGROUND: Unhealthy lifestyle behaviors among adolescents have emerged as a significant public health concern worldwide, however, there is little investigation on the impact of unhealthy behaviors on non-suicidal self-injury (NSSI), suicidal ideation (SI) and suicide attempt (SA). This study aimed to investigate the prevalence of seven unhealthy behaviors as well as their associations with NSSI, SI and SA, and to explore whether the aforementioned associations differ across sex. METHODS: A total of 74,152 adolescents were included in this study via a multi-stage, stratified cluster, random sampling method in 2021. Information about unhealthy behaviors (insufficient physical activity, current smoking, current drinking, excessive screen time, long homework time, insufficient sleep and unhealthy BMI), NSSI, SI, SA and other demographics was collected. Sampling weights were used to estimate the prevalence, and the weighted logistic regression models were performed. Stratified analyses by sex and sensitive analyses were conducted. RESULTS: Overview, the weighted prevalence of adolescents had more than five unhealthy behaviors were 5.2%, with boys showing a higher prevalence than girls (6.5% vs.3.8%). Current smoking, current drinking, excessive screen use, long homework time, insufficient sleep, and unhealthy BMI were significantly associated with NSSI, SI and SA. Moreover, adolescents with high lifestyle risk scores were associated with an increased risk of NSSI (5-7 vs. 0: OR 6.38, 95% CI 5.24-7.77), SI (5-7 vs. 0: OR 7.67, 95% CI 6.35-9.25), and SA (5-7 vs. 0: OR 9.57, 95% CI 6.95-13.17). Significant sex differences were found in the associations of unhealthy behaviors with NSSI, SI and SA. CONCLUSION: Unhealthy behaviors are quite common among Chinese adolescents. Adolescents with multiple unhealthy behaviors are associated with increased risks of NSSI, SI, and SA. The implementation of school and family-based interventions to promote healthy lifestyles is recommended as a preventive measure against self-injurious behavior and suicidality in adolescents.

Impact of Abl2/Arg deficiency on anxiety and depressive behaviors in mice.

Abl2/Arg (ABL-related gene) is a member of the Abelson family of nonreceptor tyrosine kinases, known for its role in tumor progression, metastasis, tissue injury responses, inflammation, neural degeneration, and other diseases. In this study, we developed Abl2/Arg knockout (abl2-/-) mice to explore its impact on sensory/motor functions and emotion-related behaviors. Our findings show that abl2-/- mice exhibit normal growth and phenotypic characteristics, closely resembling their wild-type (WT) counterparts. Behavioral tests, including the elevated plus maze, marble-burying behavior test, and open field test, indicated pronounced anxiety-like behaviors in abl2-/- mice compared to WT mice. Furthermore, in the tail suspension test, abl2-/- mice showed a significant decrease in mobility time, suggesting depressive-like behavior. Conversely, in the Y-maze and cliff avoidance reaction tests, no notable differences were observed between abl2-/- and WT mice, suggesting the absence of working memory deficits and impulsivity in abl2-/- mice. Proteomic analysis of the hippocampus in abl2-/- mice highlighted significant alterations in proteins related to anxiety and depression, especially those associated with the GABAergic synapse in inhibitory neurotransmission. The expression of Gabbr2 was significantly reduced in the hippocampus of abl2-/- compared to WT mice, and intraperitoneal treatment of GABA receptor agonist Gaboxadol normalized anxiety/depression-related behaviors of abl2-/- mice. These findings underscore the potential role of Abl2/Arg in influencing anxiety and depressive-like behaviors, thereby contributing valuable insights into its broader physiological and pathological functions.

A single-cell transcriptome atlas reveals the trajectory of early cell fate transition during callus induction in Arabidopsis.

The acquisition of pluripotent callus from somatic cells plays an important role in plant development studies and crop genetic improvement. This developmental process incorporates a series of cell fate transitions and reprogramming. However, our understanding of cell heterogeneity and mechanisms of cell fate transition during callus induction remains quite limited. Here, we report a time-series single-cell transcriptome experiment on Arabidopsis root explants that were induced in callus induction medium for 0, 1, and 4 days, and the construction of a detailed single-cell transcriptional atlas of the callus induction process. We identify the cell types responsible for initiating the early callus: lateral root primordium-initiating (LRPI)-like cells and quiescent center (QC)-like cells. LRPI-like cells are derived from xylem pole pericycle cells and are similar to lateral root primordia. We delineate the developmental trajectory of the dedifferentiation of LRPI-like cells into QC-like cells. QC-like cells are undifferentiated pluripotent acquired cells that appear in the early stages of callus formation and play a critical role in later callus development and organ regeneration. We also identify the transcription factors that regulate QC-like cells and the gene expression signatures that are related to cell fate decisions. Overall, our cell-lineage transcriptome atlas for callus induction provides a distinct perspective on cell fate transitions during callus formation, significantly improving our understanding of callus formation.

Transcriptome analysis reveals PRKCA as a potential therapeutic target for overcoming cisplatin resistance in lung cancer through ferroptosis.

Cisplatin-based chemotherapy is the current standard care for lung cancer patients; however, drug resistance frequently develops during treatment, thereby limiting therapeutic efficacy.The molecular mechanisms underlying cisplatin resistance remain elusive. In this study, we conducted an analysis of microarray data from the Gene Expression Omnibus (GEO) database under the accession numbers GSE21656, which encompassed expression profiling of cisplatin-resistant H460 (DDP-H460)and the parental cells (H460). Subsequently, we calculated the differentially expressed genes (DEGs) between DDP-H460 and H460. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEGs demonstrated significant impact on the Rap1, PI3K/AKT and MAPK signaling pathways. Moreover, protein and protein interaction (PPI) network analysis identified PRKCA, DET1, and UBE2N as hub genes that potentially contribute predominantly to cisplatin resistance. Ultimately, PRKCA was selected for validation due to its significant prognostic effect, which predicts unfavorable overall survival and disease-free survival in patients with lung cancer. Network analysis conducted on The Cancer Genome Atlas (TCGA) database revealed a strong gene-level correlation between PRKCA and TP53, CDKN2A, BYR2, TTN, KRAS, and PIK3CA; whereas at the protein level, it exhibited a high correlation with EGFR, Lck, Bcl2, and Syk. The in vitro experiments revealed that PRKCA was upregulated in the cisplatin-resistant A549 cells (DDP-A549), while knockdown of PRKCA increased DDP-A549 apoptosis upon cisplatin treatment. Moreover, we observed that PRKCA knockdown attenuated DDP-A549 proliferation, migration and invasion ability. Western blot analysis demonstrated that PRKCA knockdown downregulated phosphorylation of PI3K expression while upregulated the genes involved in ferroptosis signaling. In summary, our results elucidate the role of PRKCA in acquiring resistance to cisplatin and underscore its potential as a therapeutic target for cisplatin-resistant lung cancer.

Multiome in the Same Cell Reveals the Impact of Osmotic Stress on Arabidopsis Root Tip Development at Single-Cell Level.

Cell-specific transcriptional regulatory networks (TRNs) play vital roles in plant development and response to environmental stresses. However, traditional single-cell mono-omics techniques are unable to directly capture the relationships and dynamics between different layers of molecular information within the same cells. While advanced algorithm facilitates merging scRNA-seq and scATAC-seq datasets, accurate data integration remains a challenge, particularly when investigating cell-type-specific TRNs. By examining gene expression and chromatin accessibility simultaneously in 16,670 Arabidopsis root tip nuclei, the TRNs are reconstructed that govern root tip development under osmotic stress. In contrast to commonly used computational integration at cell-type level, 12,968 peak-to-gene linkage is captured at the bona fide single-cell level and construct TRNs at an unprecedented resolution. Furthermore, the unprecedented datasets allow to more accurately reconstruct the coordinated changes of gene expression and chromatin states during cellular state transition. During root tip development, chromatin accessibility of initial cells precedes gene expression, suggesting that changes in chromatin accessibility may prime cells for subsequent differentiation steps. Pseudo-time trajectory analysis reveal that osmotic stress can shift the functional differentiation of trichoblast. Candidate stress-related gene-linked cis-regulatory elements (gl-cCREs) as well as potential target genes are also identified, and uncovered large cellular heterogeneity under osmotic stress.

Potential of combined reactor and static composting applications for the removal of heavy metals and antibiotic resistance genes from chicken manure.

Chicken manure (CM) can pose a serious threat to environmental and human health, and need to be managed properly. The compost can effectively treat CM. However, there is limited research on the heavy metals and antibiotic resistance genes (ARGs) during compost CM. In this study, the combined application of reactor and static composting (RSC) was used to produce organic fertilizer of CM (OCM), and heavy metals, ARGs and bacterial community structure was investigated. The results show that RSC could be used to produce OCM, and OCM meet the National organic fertilizer standard (NY/T525-2021). Compared to the initial CM, DTPA-Cu, DTPA-Zn, DTPA-Pb, DTPA-Cr, DTPA-Ni and DTPA-As in OCM decreased by 40.83%, 23.73%, 34.27%, 38.62%, 16.26%, and 43.35%, respectively. RSC decreased the relative abundance of ARGs in CM by 84.06%, while the relative abundance of sul1 and ermC increased. In addition, the relative abundance and diversity of ARGs were mainly influenced by the bacterial community, with Actinobacteria, Firmicutes, and Proteobacteria becoming the dominant phyla during composting, and probably being the main carriers and dispersers of most of the ARGs. Network analyses confirmed that Gracilibacillus, Lactobacillus, Nocardiopsis, Mesorhizobium and Salinicoccus were the main potential hosts of ARGs, with the main potential hosts of sul1 and ermC being Mesorhizobium and Salinicoccus. The passivation and physicochemical properties of heavy metals contribute to the removal of ARGs, with sul1 and ermC being affected by the toal heavy metals. Application of RSC allows CM to produce mature, safe organic fertilizer after 32 d and reduces the risk of rebound from ARGs, but the issues of sul1 and ermC gene removal cannot be ignored.

Impact of Treatment Delay on the Prognosis of Patients with Ovarian Cancer: A Population-based Study Using the Surveillance, Epidemiology, and End Results Database.

Purpose: This study aimed to assess the impact of treatment delay on prognosis in patients with ovarian cancer. Methods: A retrospective analysis of patients with ovarian cancer in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015 was performed. Chi-square tests were used to assess baseline differences. The Kaplan-Meier method was used to evaluate the effect of different treatment intervals on survival outcomes in patients. Cox regression analyses were used to identify independent factors associated with ovarian cancer prognosis. Results: Of the 21,590 patients included, 15,675 (72.6%), 5,582 (25.9%), and 333 (1.54%) were classified into the immediate-treatment (<1 month after diagnosis), intermediate-delay (1-2 month delayed), and long-delay groups (≥3 months delayed), respectively. The 5-year probability of overall survival (OS) was 61.4% in the immediate-treatment group, decreasing to 36.4% and 34.8% in the intermediate- and long-delay groups, respectively. Similar survival differences were also reflected in cancer-specific survival (CSS), with 5-year CSS probabilities of 66.7%, 42.6%, and 41.8% in the aforementioned groups, respectively. Patients in the intermediate-delay group showed poorer OS (adjusted hazard ratio [HR], 1.06; 95% confidence interval [CI], 1.02-1.11; p=0.006) and CSS (adjusted HR, 1.06; 95% CI, 1.01-1.11; p=0.012) than immediate-treatment group. Conclusions: Patients with delayed treatment had poorer OS and CSS. The patient's waiting time from diagnosis to initial treatment should be within 1 month.

Single-cell sequencing identifies inflammation-promoting fibroblast-neutrophil interaction in peri-implantitis.

AIM: To reveal the cellular composition and molecular environment of the periodontal and peri-implant inflammatory infiltrates through a single-cell sequencing technique, which may explain the pathological difference between these two diseases. A special focus was placed on the phenotypes and potential roles of neutrophils and fibroblasts in peri-implant/periodontal tissue immunity. MATERIALS AND METHODS: High-throughput single-cell transcriptomic profiling of peri-implant tissues from patients with peri-implantitis as well as periodontal tissues from patients with periodontitis and healthy donors was performed. Immunofluorescence analysis was carried out to further validate the identified cell subtypes and their involvement in peri-implantitis and periodontitis. RESULTS: Based on our single-cell resolution analysis, a quantified proportional increase of neutrophil (Neu) subtypes was shown in peri-implantitis. Among these, a predominance of Neutro_CXCR2 was revealed. We also found the involvement of inflammation-promoting fibroblasts as well as a predominance of CXCL8+ fibroblast-CXCR2+ neutrophil interaction in peri-implantitis. CONCLUSIONS: Our study indicated that the predominance of CXCL8+ fibroblast-CXCR2+ neutrophil interaction might underline the enhanced host response in peri-implantitis compared with periodontitis. This information offers a molecular basis by which fibroblast and neutrophil subtypes might be diagnostically and therapeutically targeted in peri-implantitis.

Sfrp4 is required to maintain Ctsk-lineage periosteal stem cell niche function.

We have previously reported that the cortical bone thinning seen in mice lacking the Wnt signaling antagonist Sfrp4 is due in part to impaired periosteal apposition. The periosteum contains cells which function as a reservoir of stem cells and contribute to cortical bone expansion, homeostasis, and repair. However, the local or paracrine factors that govern stem cells within the periosteal niche remain elusive. Cathepsin K (Ctsk), together with additional stem cell surface markers, marks a subset of periosteal stem cells (PSCs) which possess self-renewal ability and inducible multipotency. Sfrp4 is expressed in periosteal Ctsk-lineage cells, and Sfrp4 global deletion decreases the pool of PSCs, impairs their clonal multipotency for differentiation into osteoblasts and chondrocytes and formation of bone organoids. Bulk RNA sequencing analysis of Ctsk-lineage PSCs demonstrated that Sfrp4 deletion down-regulates signaling pathways associated with skeletal development, positive regulation of bone mineralization, and wound healing. Supporting these findings, Sfrp4 deletion hampers the periosteal response to bone injury and impairs Ctsk-lineage periosteal cell recruitment. Ctsk-lineage PSCs express the PTH receptor and PTH treatment increases the % of PSCs, a response not seen in the absence of Sfrp4. Importantly, in the absence of Sfrp4, PTH-dependent increase in cortical thickness and periosteal bone formation is markedly impaired. Thus, this study provides insights into the regulation of a specific population of periosteal cells by a secreted local factor, and shows a central role for Sfrp4 in the regulation of Ctsk-lineage periosteal stem cell differentiation and function.

A case of NCAM1 positive lupus nephritis with NCAM1 antibody titers responsive to rituximab.

NCAM1 is a recently identified new antigen of membranous nephropathy (MN) mostly secondary to systemic lupus erythematosus (SLE) with a low positive rate of 6.6%, and its corresponding antibody was detected in patients' sera. Here, we reported a case of NCAM1-positive lupus nephritis (class Ⅴ+Ⅲ) developed from MN. The patient was refractory to multiple immunosuppressive regimens, but achieved remission after the application of rituximab as an add-on therapy and showed a reduction of anti-NCAM1 antibody and proteinuria.

Pontibacterium sinense sp. nov., a nitrate-reducing and thiosulphate-oxidizing bacterium, isolated from coastal sediment.

A novel bacterial strain, N1Y112T, was isolated from coastal sediment collected in Weihai, PR China. This Gram-stain-negative, facultatively anaerobic, motile rod-shaped bacterium exhibited the ability to oxidize thiosulphate to sulphate and reduce nitrate to ammonia through its Sox system and nitrate reduction pathway, respectively. The strain grew at 20-35 °C (optimum, 28 °C), pH 6.0-10.0 (optimum, pH 7.5) and in the presence of 1.0-5.0 % (w/v) NaCl (optimum, 3.0 %). Major fatty acids present in the strain included summed feature 8 (comprising C18 : 1 ω7c and/or C18 : 1 ω6c), summed feature 3 (comprising C16 : 1 ω7c and/or C16 : 1 ω6c) and C16 : 0. Its polar lipid profile consisted of one phosphatidylethanolamine, two unknown aminolipids, one aminophosphoglycolipid, one diphosphatidylglycerol, one phosphatidylglycerol, two unknown phospholipids and two unknown lipids. Strain N1Y112T contained ubiquinone-7 and ubiquinone-8 as isoprenoid quinones, with a genomic G+C content of 50.6 mol%. Based on phylogenetic analysis, strain N1Y112T clustered with Pontibacterium granulatum JCM 30316T being its closest relative at 97.1 % 16S rRNA gene sequence similarity. The average nucleotide identity and digital DNA-DNA hybridization values were 77.1 and 20.7 %, respectively, which suggest significant differences between genomes of N1Y112T and P. granulatum JCM 30316T. Based on the findings from its phenotypic, genotypic and phylogenetic analyses, N1Y112T is considered to represent a novel species of the genus Pontibacterium, for which the name Pontibacterium sinense sp. nov. is proposed. The type strain is N1Y112T (=KCTC 72927T=MCCC 1H00429T).

Development and validation of nomograms to recurrence and survival in patients with early-stage cervical adenocarcinoma.

PURPOSE: Cervical adenocarcinoma is one of the most common types of cervical cancer and its incidence is increasing. The biological behavior and treatment outcomes of cervical adenocarcinoma (CA) differ from those of squamous cell carcinoma (SCC). We sought to develop a model to predict recurrence and cancer-specific survival (CSS) deaths in CA patients. METHODS: 131 patients were included in model development and internal validation, and patients from the SEER database (N = 1679) were used for external validation. Multivariable Cox proportional hazards regression analysis was used to select predictors of relapse-free survival (RFS) and CSS and to construct the model, which was presented as two nomograms. Internal validation of the nomograms was performed using the bootstrap resampling method. RESULTS: Age, FIGO (International Federation of Gynecology and Obstetrics) stage, size of the tumor, lymph metastasis and depth of invasion were identified as independent prognostic factors for RFS, while age, FIGO stage, size of the tumor and number of positive LNs were identified as independent prognostic factors for CSS. The nomogram of the recurrence model predicted 2- and 5-year RFS, with optimism adjusted c-statistic of 75.41% and 74.49%. Another nomogram predicted the 2- and 5-year CSS with an optimism-adjusted c-statistic of 83.22% and 83.31% after internal validation; and 68.6% and 71.33% after external validation. CONCLUSIONS: We developed and validated two effective nomograms based on static nomograms or online calculators that can help clinicians quantify the risk of relapse and death for patients with early-stage CA.

Aberrant m5C hypermethylation mediates intrinsic resistance to gefitinib through NSUN2/YBX1/QSOX1 axis in EGFR-mutant non-small-cell lung cancer.

BACKGROUND: RNA 5-methylcytosine (m5C) modification plays critical roles in the pathogenesis of various tumors. However, the function and molecular mechanism of RNA m5C modification in tumor drug resistance remain unclear. METHODS: The correlation between RNA m5C methylation, m5C writer NOP2/Sun RNA methyltransferase family member 2 (NSUN2) and EGFR-TKIs resistance was determined in non-small-cell lung cancer (NSCLC) cell lines and patient samples. The effects of NSUN2 on EGFR-TKIs resistance were investigated by gain- and loss-of-function assays in vitro and in vivo. RNA-sequencing (RNA-seq), RNA bisulfite sequencing (RNA-BisSeq) and m5C methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR) were performed to identify the target gene of NSUN2 involved in EGFR-TKIs resistance. Furthermore, the regulatory mechanism of NSUN2 modulating the target gene expression was investigated by functional rescue and puromycin incorporation assays. RESULTS: RNA m5C hypermethylation and NSUN2 were significantly correlated with intrinsic resistance to EGFR-TKIs. Overexpression of NSUN2 resulted in gefitinib resistance and tumor recurrence, while genetic inhibition of NSUN2 led to tumor regression and overcame intrinsic resistance to gefitinib in vitro and in vivo. Integrated RNA-seq and m5C-BisSeq analyses identified quiescin sulfhydryl oxidase 1 (QSOX1) as a potential target of aberrant m5C modification. NSUN2 methylated QSOX1 coding sequence region, leading to enhanced QSOX1 translation through m5C reader Y-box binding protein 1 (YBX1). CONCLUSIONS: Our study reveals a critical function of aberrant RNA m5C modification via the NSUN2-YBX1-QSOX1 axis in mediating intrinsic resistance to gefitinib in EGFR-mutant NSCLC.

Serpin family proteins as potential biomarkers and therapeutic drugs in stroke: A systematic review and meta-analysis on clinical/preclinical studies.

BACKGROUND: Serpin is a superfamily of serine proteinase inhibitors. They have anticoagulative activities and immunoregulatory effects. The family has been widely studied in stroke patients and animal stroke models. However, results from clinical and preclinical studies are controversial. The systematic review and meta-analysis aimed to determine whether serpin activities are affected by stroke and whether members of the serpin family could be used in stroke treatment. METHODS: Literature was systematically searched in six databases until September 5, 2022. In the included studies, 47 clinical studies (8276 subjects) reported concentrations of serpin proteins in stroke patients and healthy controls. In total, 41 preclinical studies (742 animals) reported neurological outcomes in animal models with serpin treatment and vehicle. RESULTS: Meta-analysis of clinical studies showed that both ischemic (IS) and hemorrhagic stroke patients had higher thrombin-antithrombin complex (TAT) levels and lower antithrombin (AT) levels which were persistent in the acute and subacute phase of IS. Meta-analysis of preclinical studies reported the efficacy of serpins in treating stroke. C1-INH and FUT175 reduced brain infarct size and improved sensorimotor and motor behavior in a dose- and time-dependent manner in the MCAO models. CONCLUSIONS: Our study confirmed the important roles serpin family proteins played in the onset, progression, and treatment of stroke. Among serpins, AT and TAT may be used as blood biomarkers in the early diagnosis of stroke. C1-INH and FUT175 could be potential medications for IS.