Progress on the effects and underlying mechanisms of evodiamine in digestive system diseases, and its toxicity: A systematic review and meta-analysis.

BACKGROUND: Evodiamine (EVO) is one of the primary components of Evodia rutaecarpa and has been found to have a positive therapeutic effect on various digestive system diseases. However, no systematic review has been conducted on the research progress and mechanisms of EVO in relation to digestive system diseases, and its toxicity. PURPOSE: This study aimed to provide a reference for future research in this field. STUDY DESIGN: A systematic review and meta-analysis of the research progress, mechanisms, and toxicity of EVO in the treatment of digestive system diseases. METHODS: Five electronic databases were utilized to search for relevant experiments. We conducted a comprehensive review and meta-analysis of the pertinent literature following the guidelines of Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA). RESULTS: EVO's animal experiments in digestive system diseases primarily focus on colorectal cancer, gastric ulcers, liver cancer, liver fibrosis, ulcerative colitis, colitis-associated cancer, and functional gastrointestinal disorders. EVO also has positive effects on pancreatic cancer, radiation enteritis, gastric cancer, tongue squamous cancer, hepatitis B, oral cancer, and esophageal cancer in vivo. EVO's in cellular experiments primarily focus on SGC7901, HT29, HCT-116, and HepG2 cells. EVO also exhibits positive effects on SW480, LoVo, BGC-823, AGS, COLO-205, MKN45, SMMC-7721, Bel-7402, QGY7-701, PANC-1, SW1990, BxPC-3, HSC4, MC3, HONE1, and CNE1 cells in vitro. The potential common pathways include TGF-ß, PI3K-AKT, Wnt, ErbB, mTOR, MAPK, HIF-1, NOD-like receptor, NF-κB, VEGF, JAK-STAT, AMPK, Toll-like receptor, EGFR, Ras, TNF, AGE-RAGE, Relaxin, FoxO, IL-17, Hippo, and cAMP. The mechanisms of EVO on ulcerative colitis, gastric cancer, and HCT116 cells are still controversial in vivo. EVO may have a bidirectional regulatory effect on functional gastrointestinal disorders through calcium signaling. The mechanisms of EVO on HCT116, HT29, SW480, AGS, COLO-205, and SW1990 cells are still controversial in vitro. The question of whether EVO has obvious toxicity is controversial. CONCLUSION: In both cellular and animal experiments, EVO has demonstrated positive impacts on digestive system diseases. Nevertheless, additional in vivo and in vitro research is required to confirm the beneficial effects and mechanisms of EVO on digestive system diseases, as well as its potential toxicity.

Marine derived macrolide bryostatin 4 inhibits the TGF-ß signaling pathway against acute erythroleukemia.

PURPOSE: Acute erythroleukemia (AEL) is a rare and highly aggressive subtype of acute myeloid leukemia (AML) with an extremely poor prognosis when treated with available drugs. Therefore, new investigational agents capable of inducing remission are urgently required. METHODS: Bioinformatics analysis, western blot and qRT-PCR were used to reveal the potential biological mechanism of bryostatin 4 (B4), an antineoplastic macrolide derived from the marine bryozoan Bugula neritina. Then, in vivo experiments were conducted to evaluate the role of transforming growth factor (TGF)-ß signaling in the progression of AEL. RESULTS: Our results revealed that the proliferation of K562 cells and TF-1 cells was significantly inhibited by B4 at IC50 values of 37 nM and 52 nM, respectively. B4 inhibited TGF-ß signaling and its downstream pathway targets, particularly the phosphorylation of Smad2, Smad3, Ras, C-RAF, ERK1/2, and MEK. B4 also played an important role in cell invasion and migration in K562 cells and TF-1 cells by reducing the protein levels of the mesenchymal cell marker vimentin. Moreover, Flow cytometry and western blot analyses demonstrated that B4 induced apoptosis and initiated G0/G1 phase arrest by modulating mitochondrial dysfunction and cyclin-dependent kinase (CDK) expression. CONCLUSION: These findings indicated that B4 could inhibit the proliferation, migration, invasion, and TGF-ß signaling pathways of AEL cells, thus suggesting that B4 possesses therapeutic potential as a treatment for AEL.

Marine sponge-derived alkaloid inhibits the PI3K/AKT/mTOR signaling pathway against diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous non-Hodgkin lymphoma that is extremely aggressive and has an intermediate to high malignancy. Some patients still experience treatment failure, relapse, or resistance to rituximab, cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) therapy. Therefore, there is an urgent need for further research on new agents for the treatment of DLBCL. AP-48 is an aaptamine alkaloid analog with potent anti-tumor effects that originates from marine natural products. In this study, we found that AP-48 exhibits dose-dependent cytotoxicity in DLBCL cell lines. Flow cytometry showed that AP-48 induced cell cycle arrest in the G0/G1 phase in SU-DHL-4 and Farage cells and in the S phase in WSU-DLCL-2 cells. AP-48 also accelerated apoptosis via the caspase-3-mediated intrinsic apoptotic pathway. Further experiments demonstrated that AP-48 exerted its anti-DLBCL effects through the PI3K/AKT/mTOR pathway, and that the PI3K agonist YS49 partially alleviated the inhibition of cell proliferation and apoptosis induced by AP-48. Finally, in a tumor xenograft model, AP-48 inhibited tumor growth and promoted apoptosis in tumor tissues, indicating its therapeutic potential in DLBCL.

Sponge-derived alkaloid AP-7 as a sensitizer to cisplatin in the treatment of multidrug-resistant NSCLC via Chk1-dependent mechanisms.

Multidrug resistance is a substantial obstacle in treating non-small cell lung cancer (NSCLC) with therapies like cisplatin (DDP)-based adjuvant chemotherapy and EGFR-tyrosine kinase inhibitors (TKIs). Aaptamine-7 (AP-7), a benzonaphthyridine alkaloid extracted from Aaptos aaptos sponge, has been shown to exhibit a broad spectrum of anti-tumor activity. However, the anti-cancer activity of AP-7 in combination with DDP and its molecular mechanisms in multidrug-resistant NSCLC are not yet clear. Our research indicates that AP-7 bolsters the growth inhibition activity of DDP on multidrug-resistant NSCLC cells. AP-7 notably disrupts DDP-induced cell cycle arrest and amplifies DDP-induced DNA damage effects in these cells. Furthermore, the combination of AP-7 and DDP downregulates Chk1 activation, interrupts the DNA damage repair-dependent Chk1/CDK1 pathway, and helps to overcome drug resistance and boost apoptosis in multidrug-resistant NSCLC cells and a gefitinib-resistant xenograft mice model. In summary, AP-7 appears to enhance DDP-induced DNA damage by impeding the Chk1 signaling pathway in multidrug-resistant NSCLC, thereby augmenting growth inhibition, both in vitro and in vivo. These results indicate the potential use of AP-7 as a DDP sensitizer in the treatment of multidrug-resistant NSCLC.

Nocardioides bizhenqiangii sp. nov. and Nocardioides renjunii sp. nov., isolated from soil and faeces of Tibetan antelope (Pantholops hodgsonii) on the Qinghai-Tibet Plateau.

Two novel strain pairs (HM61T/HM23 and S-34T/S-58) were isolated from soil and the faeces of Tibetan antelope (Pantholops hodgsonii) collected at the Qinghai-Tibet Plateau of PR China. All four new isolates were aerobic, non-motile, Gram-stain-positive, catalase-positive, oxidase-negative, and short rod-shaped bacteria. The results of phylogenetic analysis based on the full-length 16S rRNA genes and 283 core genomic genes indicated that the four strains were separated into two independent branches belonging to the genus Nocardioides. Strains HM61T and HM23 were most closely related to Nocardioides pelophilus THG T63T (98.58 and 98.65 % 16S rRNA gene sequence similarity). Strains S-34T and S-58 were most closely related to Nocardioides okcheonensis MMS20-HV4-12T (98.89 and 98.89 % 16S rRNA gene sequence similarity). The G+C contents of the genomic DNA of strains HM61T and S-34T were 70.6 and 72.5 mol%, respectively. Strains HM61T, S-34T and the type strains of closely related species in the analysis had average nucleotide identity values of 75.4-90.5 % as well as digital DNA-DNA hybridization values between 20.1 and 40.8 %, which clearly indicated that the four isolates represent two novel species within the genus Nocardioides. The chemotaxonomic characteristics of strains HM61T and S-34T were consistent with the genus Nocardioides. The major fatty acids of all four strains were iso-C16 : 0, C17 : 1 ω8c or C18 : 1 ω9c. For strains HM61T and S-34T, MK-8(H4) was the predominant respiratory quinone, ll-2,6-diaminopimelic acid was the diagnostic diamino acid in the cell-wall peptidoglycan, and the polar lipids profiles were composed of diphosphatidylglycerol and phosphatidylglycerol. Based on phylogenetic, phenotypic, and chemotaxonomic data, we propose that strains HM61T and S-34T represent two novel species of the genus Nocardioides, respectively, with the names Nocardioides bizhenqiangii sp. nov. and Nocardioides renjunii sp. nov. The type strains are HM61T (=GDMCC 4.343T=JCM 36399T) and S-34T (=CGMCC 4.7664T=JCM 33792T).

Establishment of dual reverse transcriptase-polymerase chain reaction for detection system for Areca palm velarivirus 1.

Areca palm velarivirus 1 (APV1) is one of the main pathogen causing yellow leaf disease, and leading to considerable losses in the Areca palm industry. The detection methods for APV1 are primarily based on phenotype determination and molecular techniques, such as polymerase chain reaction (PCR). However, a single PCR has limitations in accuracy and sensitivity. Therefore, in the present study, we established a dual RT-PCR APV1-detection system with enhanced accuracy and sensitivity using two pairs of specific primers, YLDV2-F/YLDV2-R and YLDV4-F/YLDV4-R. Moreover, two cDNA fragments covering different regions of the viral genome were simultaneously amplified, with PCR amplicon of 311 and 499 bp, respectively. The dual RT-PCR detection system successfully amplified the two target regions of the APV1, demonstrating high specificity and sensitivity and compensating for the limitations of single-primer detection methods. We tested 60 Areca palm samples from different geographical regions, highlighting its advantages in that the dual RT-PCR system efficiently and accurately detected APV1 in samples across diverse areas. The dual RT-PCR APV1 detection system provides a rapid, accurate, and sensitive method for detecting the virus and offers valuable technical support for research in preventing and managing yellow leaf diseases caused by APV1 in Areca palms. Moreover, the findings of this study can serve as a reference for establishing similar plants viral detection systems in the future.

Prevotella copri alleviates hyperglycemia and regulates gut microbiota and metabolic profiles in mice.

Prevotella copri is the dominant species of the Prevotella genus in the gut, which is genomically heterogeneous and difficult to isolate; hence, scarce research was carried out for this species. This study aimed to investigate the effect of P. copri on hyperglycemia. Thirty-nine strains were isolated from healthy individuals, and three strains (HF2123, HF1478, and HF2130) that had the highest glucose consumption were selected to evaluate the effects of P. copri supplementation on hyperglycemia. Microbiomics and non-target metabolomics were used to uncover the underlying mechanisms. Oral administration of P. copri in diabetic db/db mice increased the expression and secretion of glucagon-like peptide-1 (GLP-1), significantly improved hyperglycemia, insulin resistance, and lipid accumulation, and alleviated the pathological morphology in the pancreas, liver, and colon. P. copri changed the composition of the gut microbiota of diabetic db/db mice, which was characterized by increasing the ratio of Bacteroidetes to Firmicutes and increasing the relative abundance of genera Bacteroides, Akkermansia, and Faecalibacterium. After intervention with P. copri, fecal metabolic profiling showed that fumaric acid and homocysteine contents decreased, and glutamine contents increased. Furthermore, amino acid metabolism and cAMP/PKA signaling pathways were enriched. Our findings indicate that P. copri improved glucose metabolism abnormalities in diabetic db/db mice. Especially, one of the P. copri strains, HF2130, has shown superior performance in improving hyperglycemia, which may have the potential as a probiotic against hyperglycemia. IMPORTANCE: As a core member of the human intestinal ecosystem, Prevotelal copri has been associated with glucose metabolic homeostasis in previous studies. However, these results have often been derived from metagenomic studies, and the experimental studies have been based solely on the type of strain DSM 18205T. Therefore, more experimental evidence from additional isolates is needed to validate the results according to their high genomic heterogeneity. In this study, we isolated different branches of strains and demonstrated that P. copri could improve the metabolic profile of hyperglycemic mice by modulating microbial activity. This finding supports the causal contribution of P. copri in host glucose metabolism.

An ethylene response factor AcERF116 identified from A. catechu is involved in fruitlet abscission.

Procedural abscission of outer reproductive organs during flower and fruit development occurs in most plant lineages. Undesired abscission, such as fruitlet shedding causes considerable yield loss in many fruit-producing species. Ethylene is one of the key factors regulating organ abscission. However, the participants involved in the ethylene-mediated abscission pathway remains largely unidentified. In this study, we focused on the ethylene response transcription factors (ERFs) regulating fruitlet abscission in an industrial tree species, A. catechu. A total of 165 ERF genes have been found in the A. catechu genome and eight of these showed distinct expression between the "about-to-abscise" and "non-abscised" samples. An AcERF116 gene with high expression level in the fruit abscission zone (FAZ) was selected for further study. Overexpression of the AcERF116 gene accelerated cell separation in the abscission zone (AZ) and promoted pedicel abscission in transgenic tomato lines. The PG (ploygalacturonase) activity was enhanced in the FAZs of A. catechu fruitlets during ethylene-induced fruitlet abscission, while the PME (pectin methylesterase) activity was suppressed. In addition, cytosolic alkalization was observed in the AZs during abscission in both tomato and A. catechu. Our results suggest that AcERF116 plays a critical role in the crosstalk of ethylene and fruitlet abscission in A. catechu.

Analysis of nitrogen source assimilation in industrial strains of Aspergillus oryzae.

Nitrogen source assimilation is important for the biological functions of fungi, and its pathway has been deeply studied. Aspergillus oryzae mutants defective in nitrogen source assimilation are known to grow poorly on Czapek-Dox (CD) medium. In this study, we found an industrial strain of A. oryzae that grew very poorly on a CD medium containing sodium nitrate as a nitrogen source. We used media with various nitrogen components to examine the steps affecting the nitrogen source assimilation pathway of this strain. The strain grew well on the CD medium supplied with nitrite salt or ammonium salt, suggesting that the strain was defective in nitrate assimilation step. To ascertain the gene causing the defect of nitrate assimilation, a gene expression vector harboring either niaD or crnA of A. oryzae RIB40 was introduced into the industrial strain. The industrial strain containing the crnA vector recovered its growth. This is the first report that a mutation of crnA causes poor growth on CD medium in an industrial strain of A. oryzae, and crnA can be used as a transformation marker for crnA deficient strains.

A New Method Used to Enhance the SPAIR Image of the Spine MRI.

BACKGROUND: Magnetic resonance imaging (MRI) is a handy diagnostic tool for orthopedic disorders, particularly spinal and joint diseases. METHODS: The lumbar intervertebral disc is visible in the T1 and T2 weight sequences of the spine MRI, which aids in diagnosing lumbar disc herniation, lumbar spine tuberculosis, lumbar spine tumors, and other conditions. The lumbar intervertebral disc cannot be seen accurately in the Spectral Attenuated Inversion Recovery (SPAIR) due to weaknesses in the fat and frequency offset parameters, which is not conducive to developing the intelligence diagnosis model of medical image. RESULTS: In order to solve this problem, we propose a composite framework, which is first to use the contrast limited adaptive histogram equalization (CLAHE) method to enhance the SPAIR image contrast of the spine MRI and then use the non-local means method to remove the noise of the image to ensure that the image contrast is uniform without losing details. We employ the Information Entropy (IE), Peak signal-to-noise ratio (PSNR), and feature similarity index measure (FSIM) to quantify image quality after enhancement by the composite framework. CONCLUSION: The outcomes of the experiments' output images and quantitative data indicate that our composite framework is better than others.

Isolation and absolute configuration of alkylpyridine alkaloids from the marine sponge Hippospongia lachne.

Marine sponges are well known as prolific producers of structurally diverse molecules with valuable pharmacological potential. As part of our ongoing program to discover bioactive compounds from marine sponges collected from the Xisha Islands in the South China Sea, a chemical study on the specimens of Hippospongia lachne was conducted. As a result, eight undescribed compounds, including four zwitterionic alkylpyridinium salts, hippospondines A-D (1-4), and four 3-alkylpyridine alkaloids, hippospondines E (5), F (6), and (±)-hippospondine G (7), were isolated from the marine sponge H. lachne, together with one known 3-alkylpyridine alkaloid (8). The undescribed structures were elucidated by HRESIMS, NMR, DP4+ and CP3 probability analysis, and the Snatzke's method. Hippospondines A-D (1-4) represent the rare example of inner salt type alkylpyridinium alkaloid with a farnesyl moiety. Compounds 1-3 and 8 were subjected to cytotoxic and lymphocyte proliferation assays. Compound 3 exhibited a weak promotion effect on the ConA-induced T lymphocyte proliferation.

A novel TNKS/USP25 inhibitor blocks the Wnt pathway to overcome multi-drug resistance in TNKS-overexpressing colorectal cancer.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/ß-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/ß-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APCmin/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Ultrasound study of right ventricular myocardial perfusion and functional changes in hypertrophic cardiomyopathy.

BACKGROUND: To evaluate the changes of right ventricular (RV) myocardial perfusion and function in patients with hypertrophic cardiomyopathy (HCM) by myocardial contrast echocardiography (MCE) and speckle tracking (2D-STE), and to explore the relationship between RV myocardial perfusion and strain. METHODS: Conventional ultrasound, MCE and 2D-STE were performed on 29 HCM patients and 21 healthy subjects to analyze RV myocardial perfusion, RV global strain, RV free wall strain, and strain of each segment. The correlation between RV myocardial perfusion and strain was further analyzed in HCM patients. RESULTS: MCE results showed that the regional myocardial perfusion of the RV in HCM patients was decreased. Compared with the normal control group, the mean slope (ß) in the middle and apical segments of the RV free wall, and the peak intensity (A), ß, myocardial blood flow (MBF) of the ventricular septum decreased in HCM patients (P < 0.05). RV function was impaired in HCM patients. The RV global strain (RV GLS), and the strain of RV free wall and each segment were lower than those in the normal control group (P < 0.05). Correlation analysis showed that there was a certain correlation between RV myocardial perfusion and strain, such as the ß of the whole RV in HCM group had a positive correlation with the strain of the middle segment of the interventricular septum (r = 0.550, P = 0.002). CONCLUSIONS: The regional myocardial perfusion and strain of the RV in HCM patients are reduced, and there is a positive correlation between them, suggesting that the reduction of myocardial strain may be related to the impairment of myocardial microcirculation.

Subcomponents in humic acid structure contribute to the differential responses of Aspergillus oryzae strains to humic acid.

Humic acid (HA) is a complex natural organic macromolecule, can be decomposed to low-molecular compounds by some soil fungi and then influences the growth of fungi. Aspergillus oryzae is a fungus domesticated from its ancestor, which was supposed to live in soil. Group 3 strains of A. oryzae hold fewer aflatoxin-biosynthetic genes than group 1 strains and may differently response to HA because of the deletion of some genes along with the domestication. However, effect of HA on growth of A. oryzae group 1 and group 3 strains remains unclear. In this study, four strains of A. oryzae in group 1 and four in group 3 were point inoculated on equivalent medium (pH 7.3) with two commercially available HAs. The growth of RIB40 was the most stimulated among group 1 strains and that of RIB143 was the most inhibited among group 3 strains. To identify the basis of these differences, we examined the possible effects of HA subcomponents including polyphenol and minerals on the growth of RIB40 and RIB143. Polyphenol represented by gallic acid (GA), a partial structure common with model HA, and mineral ions including Al 3+ , Ca 2+ , Ti 4+ , Mn 2+ , Sr 2+ , and Ba2+ contributed to stimulating the growth of RIB40, whereas these components generally did not affect the growth of RIB143. Thus, our findings indicate that the sub-compositions of HAs, including GA and several minerals, were the main factors driving the different responses of RIB40 and RIB143 to HAs.

Familiarity of teaching skills among general practitioners transfer training trainers in China: a cross-sectional survey.

BACKGROUND: The insufficient number of general practitioners (GPs) is a major challenge facing China's healthcare system. The purpose of the GP transfer training programme was to provide training for experienced doctors to transition to general practice. However, research on the competencies of GP transfer training trainers in teaching skills in China is limited. This cross-sectional study aimed to examine the baseline familiarity with teaching skills among Chinese GP transfer training trainers. METHODS: An online survey was conducted among trainers who participated in the 2021 Sichuan Province General Practice Training Trainer Program. The survey collected data on participants' characteristics and familiarity with 20 skills in three essential teaching knowledge areas: the core functions of primary care (five questions), preparation for lesson plan (four questions), and teaching methods (11 questions). RESULTS: In total, 305 participants completed the survey. Familiarity rates were generally low across all three essential teaching knowledge areas. No significant differences were observed in familiarity rates between the tertiary and secondary hospitals. CONCLUSION: This study revealed gaps in the teaching skills of GP transfer training trainers in China. These results suggest the necessity for targeted training programs to enhance the teaching skills and competencies of trainers.

Taxonomic descriptions of Aeromicrobium duanguangcaii sp. nov., Aeromicrobium wangtongii sp. nov. and Aeromicrobium senzhongii sp. nov.

Six Gram-stain-positive, facultative anaerobic, nonmotile and rod-shaped strains, designated zg-Y50T, zg-Y1362, zg-Y1379T, zg-Y869, zg-629T and zg-Y636, were isolated from the intestinal contents of Marmota himalayana in Qinghai Province, PR China. Strains zg-Y50T, zg-Y1379T and zg-629T exhibited the highest 16S rRNA gene sequence similarities of 99.2, 98.9 and 98.8 % to Aeromicrobium choanae 9 H-4T, Aeromicrobium ginsengisoli JCM 14732T and Aeromicrobium flavum TYLN1T, respectively. Phylogenetic and phylogenomic analyses based on the 16S rRNA gene and genomic sequences, respectively, revealed that the six strains formed three distinct clades within the genus Aeromicrobium. The genome sizes of strains zg-Y50T, zg-Y1379T and zg-629T were 3.1-3.7 Mb, with DNA G+C contents of 69.6-70.4 mol%. Average nucleotide identity and digital DNA-DNA hybridization values between each novel strain and available members of the genus Aeromicrobium were all below species thresholds. All novel strains contained MK-9 (H4) as the major menaquinone and diphosphatidylglycerol, phosphatidylglycerol and phosphatidylinositol as the polar lipids. The predominant fatty acid of the six isolates was C18 : 1 ω9c. The cell-wall peptidoglycan contained ʟʟ-diaminopimelic acid as the diagnostic diamino acid. Based on the results from this polyphasic taxonomic study, three novel species in the genus Aeromicrobium are proposed, namely, Aeromicrobium duanguangcaii sp. nov. (zg-Y50T=GDMCC 1.2981T=KCTC 49764T), Aeromicrobium wangtongii sp. nov. (zg-Y1379T=GDMCC 1.2982T=KCTC 49765T) and Aeromicrobium senzhongii sp. nov. (zg-629T=CGMCC 1.17414T=JCM 33888T).

The mitochondrial energy metabolism pathway-related signature predicts prognosis and indicates immune microenvironment infiltration in osteosarcoma.

BACKGROUND: Abnormalities in the mitochondrial energy metabolism pathways are closely related to the occurrence and development of many cancers. Furthermore, abnormal genes in mitochondrial energy metabolism pathways may be novel targets and biomarkers for the diagnosis and treatment of osteosarcoma. In this study, we aimed to establish a mitochondrial energy metabolism-related gene signature for osteosarcoma prognosis. METHODS: We first obtained differentially expressed genes based on the metastatic status of 84 patients with osteosarcoma from the TARGET database. After Venn analysis of differentially expressed genes and mitochondrial energy metabolism pathway-related genes (MMRGs), 2 key genes were obtained using univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analysis. Next, we used these 2 genes to establish a prognostic signature. Subsequent analyses elucidated the correlation between these 2 key genes with clinical features and 28 types of immune cells. Pathway changes in osteosarcoma pathogenesis under different metastatic states were clarified using gene set enrichment analysis (GSEA) of differentially expressed genes. RESULTS: A gene signature composed of 2 key prognosis-related genes (KCNJ5 and PFKFB2) was identified. A risk score was calculated based on the gene signature, which divided osteosarcoma patients into low- or high-risk groups that showed good and poor prognosis, respectively. High expression of these 2 key genes is associated with low-risk group in patients with osteosarcoma. We constructed an accurate nomogram to help clinicians assess the survival time of patients with osteosarcoma. The results of immune cell infiltration level showed that the high-risk group had lower levels of immune cell infiltration. GSEA revealed changes in immune regulation and hypoxia stress pathways in osteosarcoma under different metastatic states. CONCLUSION: Our study identified an excellent gene signature that could be helpful in improving the prognosis of patients with osteosarcoma.

Marnyiella aurantia, gen. nov., sp. nov., a novel bacterial species of the family Weeksellaceae that could produce flexirubin type pigments.

Two Gram-stain-negative, non-spore-forming, rod-shaped, and obligately aerobic bacteria, designated strains CX-624T and cx-311, were isolated from soil samples in Qinghai Province, China. The two strains grew best at 28 °C on the plate with Tryptone soya agar (TSA). Cells formed circular, convex, translucent, smooth, and orange colonies with approximately 1.0 mm diameter after 2 days of incubation on TSA at 28 °C. The strains were oxidase-negative and catalase-positive. The predominant cellular fatty acids were iso-C15 : 0 and anteiso-C15 : 0, and major polar lipids included phosphatidylethanolamine, an unidentified aminophospholipid, four unidentified lipids and an aminolipid. MK-6 was the sole menaquinone in strain CX-624T. Comparative analysis of the nearly full-length 16S rRNA gene sequences showed strains CX-624T and cx-311 were member of the family Weeksellaceae, with the highest similarity to Kaistella haifensis H38T (96.66 %), Epilithonimonas pallida DSM 18015T (96.59 %), and Chryseobacterium gambrini DSM 18014T (96.53 %). Both phylogenetic analysis of the 16S rRNA gene and 177 core genes revealed that strains CX-624T and cx-311 formed an independent clade. Average nucleotide identity values (< 72.64 %), average amino-acid identity values (<72.61 %) and digital DNA-DNA hybridization (< 21.10 %) indicated that the strains CX-624T and cx-311 should constitute a novel genus. The DNA G+C contents of strains CX-624T and cx-311 were 43.0 mol% and 42.7 mol%. According to the data obtained in this study, strain CX-624T represents a novel species belonging to a novel genus of the Weeksellaceae, for which the name Marnyiella aurantia gen. nov., sp. nov. is proposed. The type strain is CX-624T (=GDMCC 1.1714T = JCM 33925T).

Neural correlates of central pain sensitization in chronic low back pain: a resting-state fMRI study.

PURPOSE: The objective of this study is to explore the neural correlates of pain sensitization in patients with chronic low back pain (cLBP). While the association between cLBP and pain sensitization has been widely reported, the underlying brain mechanism responsible for this relationship requires further investigation. METHODS: Our study included 56 cLBP patients and 56 healthy controls (HC). Functional magnetic resonance imaging data were obtained, and the voxel-wise amplitude of low-frequency fluctuation (ALFF) was calculated to identify brain alterations in cLBP patients compared to HC groups. Pearson correlation coefficients were computed to explore the association between clinical data and brain alterations. Furthermore, mediation analyses were performed to investigate the path association between brain alterations and pain-related behaviors. RESULTS: Our findings revealed that patients with cLBP exhibited higher sensitivity, attention, and catastrophizing tendencies towards pain compared to HC. Furthermore, cLBP patients displayed significantly higher ALFF in various brain regions within the "pain matrix" and the default mode network when compared to HC. The altered precuneus ALFF was positively correlated with pain intensity (R = 0.51, P<0.001) and was negatively correlated with pain sensitivity (R = -0.43, P<0.001) in cLBP patients. Importantly, the effect of altered precuneus ALFF on pain intensity was mediated by pain threshold in these patients. CONCLUSION: Our study suggests that altered neural activity in the precuneus may contribute to pain hypersensitivity, which further exacerbating pain in cLBP patients.

Neisseria lisongii sp. nov. and Neisseria yangbaofengii sp. nov., isolated from the respiratory tracts of marmots.

Four Gram-stain-negative, oxidase-positive, non-motile, cocci-shaped bacteria strains (ZJ106T, ZJ104, ZJ785T and ZJ930) were isolated from marmot respiratory tracts. Phylogenetic analyses based on 16S rRNA genes, 53 ribosomal protein sequences and 441 core genes supported that all four strains belonged to the genus Neisseria with close relatives Neisseria weixii 10022T and Neisseria iguanae ATCC 51483T. Average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values were below the species-level thresholds (95-96 % for ANI, and 70 % for dDDH). The major fatty acids of all four strains were C16 : 1 ω7c /C16 : 1 ω6c, C16 : 0 and C18 : 1 ω9c. Major polar lipids were composed of diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol. MK-8 was the major menaquinone. Based on Virulence Factor Database analysis, the four strains were found to contain NspA and PorB H-factor binding proteins that promote evasion of host immunity. Strains ZJ106T and ZJ104 contained structures similar to the capsule synthesis manipulator of Neisseria meningitidis. Based on phenotypic and phylogenetic evidence, we propose that strains ZJ106T and ZJ785T represent two novel species of the genus Neisseria, respectively, with the names Neisseria lisongii sp. nov. and Neisseria yangbaofengii sp. nov. The type strains are ZJ106T (=GDMCC 1.3111T=JCM 35323T) and ZJ785T (=GDMCC 1.1998T=KCTC 82336T).