Cut-off values of haemoglobin and clinical outcomes in incident peritoneal dialysis: the PDTAP study.

BACKGROUND: To explore the cut-off values of haemoglobin (Hb) on adverse clinical outcomes in incident peritoneal dialysis (PD) patients based on a national-level database. METHODS: The observational cohort study was from the Peritoneal Dialysis Telemedicine-assisted Platform (PDTAP) dataset. The primary outcomes were all-cause mortality, major adverse cardiovascular events (MACE) and modified MACE (MACE+). The secondary outcomes were the occurrences of hospitalization, first-episode peritonitis and permanent transfer to haemodialysis (HD). RESULTS: A total of 2591 PD patients were enrolled between June 2016 and April 2019 and followed up until December 2020. Baseline and time-averaged Hb <100 g/l were associated with all-cause mortality, MACE, MACE+ and hospitalizations. After multivariable adjustments, only time-averaged Hb <100 g/l significantly predicted a higher risk for all-cause mortality {hazard ratio [HR] 1.83 [95% confidence interval (CI) 1.19-281], P = .006}, MACE [HR 1.99 (95% CI 1.16-3.40), P = .012] and MACE+ [HR 1.77 (95% CI 1.15-2.73), P = .010] in the total cohort. No associations between Hb and hospitalizations, transfer to HD and first-episode peritonitis were observed. Among patients with Hb ≥100 g/l at baseline, younger age, female, use of iron supplementation, lower values of serum albumin and renal Kt/V independently predicted the incidence of Hb <100 g/l during the follow-up. CONCLUSION: This study provided real-world evidence on the cut-off value of Hb for predicting poorer outcomes through a nation-level prospective PD cohort.

Tracking Extensive Portfolio of Cyanotoxins in Five-Year Lake Survey and Identifying Indicator Metabolites of Cyanobacterial Taxa.

Cyanobacterial blooms require monitoring, as they pose a threat to ecosystems and human health, especially by the release of toxins. Along with widely reported microcystins, cyanobacteria coproduce other bioactive metabolites; however, information about their dynamics in surface waters is sparse. We investigated dynamics across full bloom successions throughout a five-year lake monitoring campaign (Greifensee, Switzerland) spanning 150 sampling dates. We conducted extensive suspect screening of cyanobacterial metabolites using the database CyanoMetDB. Across all 850 samples, 35 metabolites regularly co-occurred. Microcystins were present in 70% of samples, with [d-Asp3,(E)-Dhb7]MC-RR reaching concentrations of 70 ng/L. Anabaenopeptins, meanwhile, were detected in 95% of all samples with concentrations of Oscillamide Y up to 100-fold higher than microcystins. Based on LC-MS response and frequency, we identified indicator metabolites exclusively produced by one of three cyanobacteria isolated from the lake, these being [d-Asp3,(E)-Dhb7]MC-RR from Planktothrix sp. G2020, Microginin 761B from Microcystis sp. G2011, and Ferintoic acid B from Microcystis sp. G2020. These indicators showed distinct temporal trends and peaking seasons that reflect the variance in either the abundance of the producing cyanobacteria or their toxin production dynamics. Our approach demonstrates that selecting high LC-MS response and frequent and species-specific indicator metabolites can be advantageous for cyanobacterial monitoring.

Comparison of the efficacy of neuronavigation-assisted intracerebral hematoma puncture and drainage with neuroendoscopic hematoma removal in treatment of hypertensive cerebral hemorrhage.

OBJECTIVE: To compare neuronavigation-assisted intracerebral hematoma puncture and drainage with neuroendoscopic hematoma removal for treatment of hypertensive cerebral hemorrhage. METHOD: Ninety-one patients with hypertensive cerebral hemorrhage admitted to our neurosurgery department from June 2022 to May 2023 were selected: 47 patients who underwent endoscopic hematoma removal with the aid of neuronavigation in observation Group A and 44 who underwent intracerebral hematoma puncture and drainage in control Group B. The duration of surgery, intraoperative bleeding, hematoma clearance rate, pre- and postoperative GCS score, National Institutes of Health Stroke Scale (NIHSS) score, mRS score and postoperative complications were compared between the two groups. RESULTS: The duration of surgery, intraoperative bleeding and hematoma clearance were significantly lower in Group B than in Group A (p < 0.05). Conversely, no significant differences in the preoperative, 7-day postoperative, 14-day postoperative or 1-month postoperative GCS or NIHSS scores or the posthealing mRS score were observed between Groups A and B. However, the incidence of postoperative complications was significantly greater in Group B than in Group A (p < 0.05), with the most significant difference in incidence of intracranial infection (p < 0.05). CONCLUSION: Both neuronavigation-assisted intracerebral hematoma puncture and drainage and neuroendoscopic hematoma removal are effective at improving the outcome of patients with hypertensive cerebral hemorrhage. The disadvantage of neuronavigation is that the incidence of complications is significantly greater than that of other methods; postoperative care and prevention of complications should be strengthened in clinical practice.

Hydrochemical characterization and health risk assessment of different types of water bodies in Fenghuang Mountain Area, Northeast China.

Groundwater, as an essential resource, holds significant importance for human production and livelihoods. With the deterioration of the water environment, the issue of groundwater quality has become an urgent international concern. This study focused on the Fenghuang Mountain Area (FMA) and collected a total of 41 sets of samples including pore groundwater (PGW), fissure groundwater (FGW), karst groundwater (KGW), and river water (RW). Hydrochemical analysis methods were employed to identify the hydrochemical characteristics and controlling factors. The entropy-weighted water quality index (EWQI) and health risk assessment model were utilized to assess the groundwater quality and nitrate health risk, respectively. The results indicated that the dominant anion and cation in both groundwater and surface water in the FMA were HCO3- and Ca2+, respectively, with the main hydrochemical type being HCO3-Ca. Groundwater and surface water in the FMA were primarily controlled by rock weathering process, with ion concentrations influenced mainly by the dissolution of halite, sylvite, carbonates (calcite and dolomite), silicates, and gypsum, as well as by reverse anion exchange process. PGW was significantly affected by agricultural activities, with NO3- concentration closely related to human activities. The water quality of FGW was relatively good, with Class I and Class II water accounting for the highest proportion, reaching 84.62%. The high-value area of EWQI in PGW was influenced by human activities. The impact of nitrate health risk on children was significantly greater than on adults, with FGW having the lowest health risk and PGW having the highest health risk. The research results can provide important guarantees for the rational development and utilization of water resources in the FMA and the sustainable development of the economy in Northeast China.

Targeting feedback activation of signaling transduction pathways to overcome drug resistance in cancer.

Dysregulation or aberrant signaling transduction contributes to tumorigenesis. Targeting these abnormal signaling pathways becomes an effective anticancer strategy. However, feedback activation or crosstalk between signaling pathways drives adaptive drug resistance which causes failure of cancer therapy. In this review article, we summarized treatments that cause feedback activation of AKT, ERK, STAT3, EGFR, FGFR, and HER2/3 signaling pathways and the combination therapy to enhance anti-tumor effect or to overcome drug resistance, to explore the underlying mechanisms that define the protein molecules participated or regulated the feedback activation. In addition, we reviewed clinical trials that employ combination treatments to suppress feedback activation and improve therapeutic efficacy of cancer treatments.

Discovery of a Novel Ubenimex Derivative as a First-in-Class Dual CD13/Proteasome Inhibitor for the Treatment of Cancer.

The CD13 inhibitor ubenimex is used as an adjuvant drug with chemotherapy for the treatment of cancer due to its function as an immunoenhancer, but it has limitations in its cytotoxic efficacy. The proteasome inhibitor ixazomib is a landmark drug in the treatment of multiple myeloma with a high anti-cancer activity. Herein, we conjugated the pharmacophore of ubenimex and the boric acid of ixazomib to obtain a dual CD13 and proteasome inhibitor 7 (BC-05). BC-05 exhibited potent inhibitory activity on both human CD13 (IC50 = 0.13 µM) and the 20S proteasome (IC50 = 1.39 µM). Although BC-05 displayed lower anti-proliferative activity than that of ixazomib in vitro, an advantage was established in the in vivo anti-cancer efficacy and prolongation of survival time, which may be due to its anti-metastatic and immune-stimulating activity. A pharmacokinetic study revealed that BC-05 is a potentially orally active agent with an F% value of 24.9%. Moreover, BC-05 showed more favorable safety profiles than those of ixazomib in preliminary toxicity studies. Overall, the results indicate that BC-05 is a promising drug candidate for the treatment of multiple myeloma.

ZBTB7A, a miR-144-3p targeted gene, accelerates bladder cancer progression via downregulating HIC1 expression.

BACKGROUND: Zinc finger and BTB domain-containing 7A (ZBTB7A) is a member of the POK family of transcription factors that plays an oncogenic or tumor-suppressive role in different cancers depending on the type and genetic context of cancer. However, the function and molecular mechanism of ZBTB7A in bladder cancer (BC) remain elusive. METHODS: The role of ZBTB7A in bladder cancer was detected by colony formation, transwell, and tumor formation assays. The expression levels of ZBTB7A, HIC1, and miR-144-3p were analyzed by qRT-PCR and Western blot. Bioinformatics analysis and a dual-luciferase reporter assay were used to assess the effect of ZBTB7A on the promoter activity of HIC1. RESULTS: The present study revealed that knockdown of ZBTB7A suppressed BC cell growth and migration, as indicated by an approximately 50% reduction in the number of colonies and an approximately 70% reduction in the number of migrated cells. Loss of ZBTB7A inhibited tumor growth in vivo, resulting in a 75% decrease in tumor volume and an 80% decrease in tumor weight. Further mechanistic studies revealed that ZBTB7A bound to the hypermethylated in cancer 1 (HIC1) promoter and downregulated HIC1 expression, accelerating the malignant behavior of BC. Increased expression of ZBTB7A in BC tissues was negatively corrected with the expression of HIC1. Moreover, ZBTB7A was a target of miR-144-3p, which decreased ZBTB7A expression in BC. CONCLUSION: Our data demonstrate that ZBTB7A, a targeted gene of miR-144-3p, promoted tumorigenesis of BC through downregulating HIC1 expression.

Telemedicine and Clinical Outcomes in Peritoneal Dialysis: A Propensity-Matched Study.

INTRODUCTION: Telemedicine (TM) has shown to provide potential benefits on clinical outcomes in patients with chronic kidney disease but limited evidences published in the peritoneal dialysis (PD) population. This study aimed to explore the long-term effects of TM on the mortality and technique failure. METHODS: The Peritoneal Dialysis Telemedicine-assisted Platform Cohort Study (PDTAP Study) was conducted prospectively in 27 hospitals in China since 2016. Patient and practice data were collected through the doctor-end of the TM app (Manburs) for all participants. TM including self-monitoring records, on-line education materials, and real-time physician-patient contact was only performed for the patient-end users of the Manburs. The primary outcome was all-cause mortality. The secondary outcomes were cause-specific mortality and all-cause and cause-specific permanent transfer to hemodialysis. RESULTS: A total of 7,539 PD patients were enrolled between June 2016 and April 2019, with follow-up till December 2020. Patients were divided into two cohorts: TM group (39.1%) and non-TM group (60.9%). A propensity score was used to create 2,160 matched pairs in which the baseline covariates were well-balanced. There were significantly lower risks of all-cause mortality (HR 0.59 [0.51, 0.67], p < 0.001), CVD mortality (HR 0.59 [0.49, 0.70], p < 0.001), all-cause transfer to hemodialysis (0.57 [0.48, 0.67], p < 0.001), transfer to hemodialysis from PD-related infection (0.67 [0.51, 0.88], p = 0.003), severe fluid overload (0.40 [0.30, 0.55], p < 0.001), inadequate solute clearance (0.49 [0.26, 0.92], p = 0.026), and catheter-related noninfectious complications (0.41 [0.17, 0.97], p = 0.041) in the TM group compared with the non-TM group. CONCLUSION: This study indicated real-world associations between TM usage and reduction in patient survival and technique survival through a multicenter prospective cohort.

Nocardioides nematodiphilus sp. nov., isolated from rhizosphere of Arabidopsis thaliana.

An actinobacterial strain, designated R-N-C8T, was isolated from the rhizosphere soil of Arabidopsis thaliana collected in Yunnan Province, south-west China. Based on the results of 16S rRNA gene sequence analysis, strain R-N-C8T had highest similarity to Nocardioides terrae CGMCC 1.7056T (96.5%), Nocardioides opuntiae KCTC 19804T (96.3%) and Nocardioides currus IB-3T (96.1%), and lower than 96.0 % similarity to other members of the genus Nocardioides. Phylogenetic trees based on 16S rRNA gene sequences indicated that strain R-N-C8T formed an isolated branch with N. terrae CGMCC 1.7056T and N. opuntiae KCTC 19804T. The polar lipids contained phosphatidylglycerol, diphosphatidylglycerol, one unidentified phosphoglycolipid and four unidentified phospholipids in the cellular membrane. The major fatty acids were identified as iso-C16 : 0, anteiso-C17 : 0, iso-C17 : 0, summed feature 9 (iso-C17 : 1 ω9c and/or C16 : 0 10-methyl) and iso-C15 : 0. The predominant respiratory quinone was MK-8(H4) and ll-diaminopimelic acid was the diagnostic diamino acid in the cell-wall peptidoglycan. The genomic DNA G+C content was 70.9 mol%. The orthologous average nucleotide identiy values between N. terrae CGMCC 1.7056T, N. currus IB-3T and strain R-N-C8T were 77.1 and 75.1 %, respectively. DNA-DNA hybridization values between N. terrae CGMCC 1.7056T, N. currus IB-3T and strain R-N-C8T were 20.7 and 19.9 % respectively. Data from phenotypic and genotypic analyses supported that strain R-N-C8T represents a new species of Nocardioides, for which the name Nocardioides nematodiphilus sp. nov. is proposed. The type strain is R-N-C8T (=CGMCC 1.18723T= KCTC 49528T).

WY-14643 attenuates lipid deposition via activation of the PPARα/CPT1A axis by targeting Gly335 to inhibit cell proliferation and migration in ccRCC.

BACKGROUND: Histologically, cytoplasmic deposits of lipids and glycogen are common in clear cell renal cell carcinoma (ccRCC). Owing to the significance of lipid deposition in ccRCC, numerous trials targeting lipid metabolism have shown certain therapeutic potential. The agonism of peroxisome proliferator-activated receptor-α (PPARα) via ligands, including WY-14,643, has been considered a promising intervention for cancers. METHODS: First, the effects of WY-14,643 on malignant behaviors were investigated in ccRCC in vitro. After RNA sequencing, the changes in lipid metabolism, especially neutral lipids and glycerol, were further evaluated. Finally, the underlying mechanisms were revealed. RESULTS: Phenotypically, the proliferation and migration of ccRCC cells treated with WY-14,643 were significantly inhibited in vitro. A theoretical functional mechanism was proposed in ccRCC: WY-14,643 mediates lipid consumption by recognizing carnitine palmitoyltransferase 1 A (CPT1A). Activation of PPARα using WY-14,643 reduces lipid deposition by increasing the CPT1A level, which also suppresses the NF-κB signaling pathway. Spatially, WY-14,643 binds and activates PPARα by targeting Gly335. CONCLUSION: Overall, WY-14,643 suppresses the biological behaviors of ccRCC in terms of cell proliferation, migration, and cell cycle arrest. Furthermore, its anticancer properties are mediated by the inhibition of lipid accumulation, at least in part, through the PPARα/CPT1A axis by targeting Gly335, as part of the process, NF-κB signaling is also suppressed. Pharmacological activation of PPARα might offer a new treatment option for ccRCC.

Overexpression of Stat3 increases circulating cfDNA in breast cancer.

PURPOSE: Current studies on circulating cell-free DNA (cfDNA) have been focusing on its potential as biomarkers in liquid biopsy by detecting its content or genetic and epigenetic changes for the evaluation of tumor burden and therapeutic efficacy. However, the regulatory mechanism of cfDNA release remains unclear. Stat3 has been documented as an oncogene for the development and metastasis of breast cancer cells. In this study, we investigated whether Stat3 affects the release of cfDNA into blood and its association with the number of circulating tumor cells (CTCs). METHODS: The cfDNA level in plasma of patients with breast cancer and healthy volunteers were determined by quantitative real-time PCR. Three mouse breast cancer models with different Stat3 expression were generated and used to established three breast cancer orthotopic animal models to examine the effect of Stat3 on cfDNA release in vivo. Stat3 mediated Epithelial-mesenchymal phenotype transition of CTCs was determined by immunofluorescence assay and Western blot assay. RESULTS: The data showed that Stat3 increased circulating cfDNA, which is correlated with the increased volume of primary tumors and number of CTCs, accompanied with the dynamic EMT changes regulated by Snail induction. Furthermore, the high level of total circulating cfDNA and Stat3-cfDNA in patients with breast cancer were detected by quantitative real-time PCR using GAPDH and Stat3 primers. CONCLUSION: Our results suggested that Stat3 increases the circulating cfDNA and CTCs in breast cancer.

Nocardioides stalactiti sp. nov., isolated from a cave stalactite surface.

An aerobic, rod-shaped, Gram-stain-positive, actinobacterial strain, designated 1.0914T, was isolated from a stalactite sample collected from a cave located in Guizhou Province, southwest PR China. Based on 16S rRNA gene sequence analysis, strain 1.0914T shared highest similarities values with Nocardioides pelophilus CGMCC 4.7388T (97.7 %), Nocardioides immobilis CCTCC AB 2017083T (97.5 %) and Nocardioides silvaticus CCTCC AB 2018079T (97.3 %) and values lower than 97.0 % to other members of the genus Nocardioides. Phylogenetic trees based on 16S rRNA gene sequences indicated that strain 1.0914T formed an isolated branch with N. pelophilus CGMCC 4.7388T, N. immobilis CCTCC AB 2017083T and N. silvaticus CCTCC AB 2018079T. The polar lipids contained phosphatidylglycerol, diphosphatidylglycerol, phosphatidylinositol and one unidentified phospholipid in the cellular membrane. The major fatty acids were identified as iso-C16 : 0, C18 : 1 ω9c, C17 : 1 ω8c and C16 : 0. The predominant respiratory quinone was MK-8(H4) and ll-diaminopimelic acid was the diagnostic diamino acid in the cell-wall peptidoglycan. The genomic DNA G+C content was 71.1 mol%. The orthologous average nucleotide identiy values between N. pelophilus CGMCC 4.7388T, N. immobilis CCTCC AB 2017083T, N. silvaticus CCTCC 2018079T and strain 1.0914T were 82.3, 81.7 and 81.9 % respectively. DNA-DNA hybridization values between N. pelophilus CGMCC 4.7388T, N. immobilis CCTCC AB 2017083T, N. silvaticus CCTCC 2018079T and strain 1.0914T were 25.2, 24.6 and 24.5 % respectively. The phylogenetic, phenotypic and chemotaxonomic data supported the classification of strain 1.0914T as representing a new species of Nocardioides, for which the name Nocardioides stalactiti sp. nov. is proposed. The type strain is 1.0914T (=CCTCC AB 2018266T=KCTC 49243T).

Design, synthesis and biological evaluation of hybrid of ubenimex-fluorouracil for hepatocellular carcinoma therapy.

In our previous study, we discovered a ubenimex-fluorouracil (5FU) conjugates BC-02, which displays significant in vivo anti-tumor activity, however, the instability of BC-02 in plasma limits its further development as a drug candidate. Herein, we designed and synthesized four novel ubenimex-5FU conjugates by optimizing the linkers between ubenimex and 5FU based on BC-02. Representative compound 20 is more stable than BC-02 in human plasma and displays about 100 times higher CD13 inhibitory activity than the positive control ubenimex. Meanwhile, the antiproliferative activity of 20 was comparable with 5FU in vitro. The preliminary mechanism study indicated that compound 20 exhibited significant anti-invasion and anti-angiogenesis activities in vitro. Furthermore, compound 20 obviously inhibits tumor growth and metastasis in vivo and prolong the survival time of tumor-bearing mice. Our study may have an important implication reference for the design of more druglike mutual prodrug, and compound 20 can be used as a lead compound for further design and development.

CD13 Induces Autophagy to Promote Hepatocellular Carcinoma Cell Chemoresistance Through the P38/Hsp27/CREB/ATG7 Pathway.

The chemoresistance of hepatocellular carcinoma (HCC) is a serious problem that directly hinders the effect of chemotherapeutic agents. We previously reported that Aminopeptidase N (CD13) inhibition can enhance the cytotoxic efficacy of chemotherapy agents. In the present study, we use liver cancer cells to explore the molecular mechanism accounting for the relationship between CD13 and chemoresistance. We demonstrate that CD13 overexpression activates the P38/heat shock protein 27/cAMP response element-binding protein (CREB) signaling pathway to limit the efficacy of cytotoxic agents. Moreover, blockade of P38 or CREB sensitizes HCC cells to 5-fluorouracil. Then we reveal that CREB binds to the autophagy related 7 (ATG7) promoter to induce autophagy and promote HCC cell chemoresistance. CD13 inhibition also downregulates the expression of ATG7, autophagy, and tumor cell growth in vivo. Overall, the combination a CD13 inhibitor and chemotherapeutic agents may be a potential strategy for overcoming drug resistance in HCC. SIGNIFICANCE STATEMENT: Our study demonstrates that Aminopeptidase N (CD13) promotes hepatocellular carcinoma (HCC) cell chemoresistance via the P38/heat shock protein 27/cAMP response element-binding protein (CREB) pathway. CREB regulates autophagy related 7 transcription and expression to induce autophagy. Our results collectively suggest that CD13 may serve as a potential target for overcoming HCC resistance.

Asticcacaulis tiandongensis sp. nov., a new member of the genus Asticcacaulis, isolated from a cave soil sample.

A Gram-stain negative, aerobic, motile and rod-shaped bacterium, designated strain 3.1105T, was isolated from a karst district soil sample collected from Tiandong cave, Guizhou province, south-west PR China. The isolate grew at 10-40 °C and pH 5.0-8.0 and tolerated up to 1 % NaCl (w/v) on R2A medium, with optimal growth at 25-30 °C, pH 7.0 and 0 % NaCl (w/v). Cells showed oxidase-positive and catalase-positive reactions. The respiratory quinone was Q-10. The predominant cellular fatty acids contained C18 : 1ω7c 11-methyl, summed feature 8 (C18 : 1ω7c or C18 : 1ω6c), C16 : 0 and C17 : 0. The major polar lipids were phosphatidylglycerol and monoglycosyldiglycerides. The genomic DNA G+C content was 56.0 mol%. Phylogenetic analysis based on 16S rRNA gene sequences indicated that 3.1105T should be affiliated to the genus Asticcacaulis and showed highest 16S rRNA gene sequence similarity values with Asticcacaulis excentricus CB 48T (96.0 %), Asticcacaulis endophyticus ZFGT-14T (95.3 %) and lower than 95.3 % similarity to other species of the genus Asticcacaulis. The polyphasic taxonomic characteristics indicated that strain 3.1105T represents a novel species of the genus Asticcacaulis, for which the name Asticcacaulis tiandongensis sp. nov., (type strain 3.1105T=KCTC 62978T=CCTCC AB 2018268T) is proposed.

Luteimonas lumbrici sp. nov., a novel bacterium isolated from wormcast.

A Gram-stain-negative, yellow-green bacterium, designated 1.1416T, was isolated from wormcast of Eisenia foetida. The strain was non-motile, rod-shaped, and grew optimally on NA medium at 30 °C, pH 7.0 and with 0 % (w/v) NaCl. On the basis of the 16S rRNA gene sequence and phylogenetic analysis, 1.1416T showed the highest degree of 16S rRNA gene sequence similarity to Luteimonas arsenica 26-35T (96.2 %), followed by Luteimonas lutimaris G3T (96.1 %). The respiratory quinone of 1.1416T was ubiquinone-8 (Q-8), and its major cellular fatty acids were iso-C15 : 0 (39.8 %), summed feature 9 (iso-C17 : 1 ω9c or C16 : 0 10-methyl) (18.6 %). The major polar lipids of 1.1416T were phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine and six unidentified phospholipids. The genomic DNA G+C content of 1.1416T was 71.0 mol%. According to the results of the phenotypic and chemotaxonomic phylogenetic analyses, strain 1.1416T represents a novel species of the genus Luteimonas, for which the name Luteimonas lumbrici sp. nov. is proposed, with strain 1.1416T (=KCTC 62979T=CCTCC AB 2018348T) as the type strain.

Sphingobacterium cavernae sp. nov., a novel bacterium isolated from soil sampled at Tiandong Cave.

A Gram-stain-negative, non-motile and rod-shaped bacterium, designated strain 5.0403-2T, was isolated from a cave soil sample collected from Tiandong Cave, Guizhou Province, south-west PR China. Cells showed positive oxidase and catalase reactions. The predominant isoprenoid quinone was MK-7. The major fatty acids were identified as iso-C15 : 0, summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c), iso-C17 : 0 3OH and summed feature 9 (iso-C17 : 1 ω9c or C16 : 0 10-methyl). The cellular polar lipids contained phosphatidylethanolamine, one unidentified phospholipid, three unidentified phosphoglycolipids and four unidentified lipids. The genomic DNA G+C content was 36.0 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain 5.0403-2T should be assigned to the genus Sphingobacterium. Results of 16S rRNA gene sequence similarity analysis showed that strain 5.0403-2T was most similar to Sphingobacterium bovisgrunnientis KCTC 52685T (98.7 %), Sphingobacterium composti KCTC 12578T (98.0 %) and Sphingobacterium alimentarium DSM 22362T (97.3 %) and less than 95.0 % similar to other species of the genus Sphingobacterium. The average nucleotide identity values between strain 5.0403-2T and S. bovisgrunnientis KCTC 52685T, S. composti KCTC 12578T and S. alimentarium DSM 22362T were 94.2, 82.3 and 77.2 % respectively. The digitalDNA-DNA hybridization values between strain 5.0403-2T and S. bovisgrunnientis KCTC 52685T, S. composti KCTC 12578T and S. alimentarium DSM 22362T were 68.4, 25.6 and 20.7 %. These results indicated that the isolate represented a novel genomic species. The polyphasic taxonomic characteristics indicated that strain 5.0304-2T represents a novel species of the genus Sphingobacterium, for which the name Sphingobacterium cavernae sp. nov. (type strain 5.0403-2T=KCTC 62981T=CCTCC AB 2019257T) is proposed.

Leucine aminopeptidase 3 promotes migration and invasion of breast cancer cells through upregulation of fascin and matrix metalloproteinases-2/9 expression.

Overexpression of leucine aminopeptidase 3 (LAP3) is involved in proliferation, migration, and invasion of several tumor cells and plays a crucial role in tumor metastasis. However, the related mechanism remains unknown. In this study, we used MDA-MB-231 and MCF7 breast cancer cell lines to explore the role of LAP3 in the regulation of cancer cell migration and invasion by employing the natural LAP3 inhibitor bestatin and a lentivirus vector that overexpresses or knocks down LAP3. Bestatin inhibited tumor cell migration and invasion in a dose-dependent manner. Western blot assay showed that bestatin and knockdown of LAP3 upregulated phosphorylation of Hsp27 and downregulated expression of fascin. Phosphorylation of Akt and expression of matrix metalloproteinase-2/9 can also be downregulated. LAP3 overexpression showed the opposite results. Immunohistochemistry analysis was conducted to detect expression levels of LAP3 in breast cancer tissues. High LAP3 expression was correlated with the grade of malignancy. Findings of this study uncovered the molecular mechanism of LAP3 on breast cancer metastasis and indicated that LAP3 may act as a potential antimetastasis therapeutic target.

Clinical analysis of adrenal lesions larger than 5 cm in diameter (an analysis of 251 cases).

BACKGROUND: To describe the pathological distribution, imaging manifestations, and surgical managements and prognosis of large adrenal tumors (LATs) ≥ 5 cm METHODS: A total of 251 patients with LATs were analyzed on the basis of pathological or clinical diagnosis. Regarding surgery, open adrenalectomy was performed on 89 patients, and laparoscopic adrenalectomy was performed on 89 patients. Thirty-two patients with bilateral tumors were analyzed in terms of clinical characteristics. The survival rate was determined for 43 patients with adrenal metastases and 29 patients with primary adrenal malignancies. The CT characteristics including tumor diameter, shape, edge, heterogeneity, necrosis, calcification, pre-contrast attenuation, and contrast attenuation were analyzed for 117 patients. RESULTS: The majority of LATs were still benign, but they had a higher probability to be malignant. Benign LATs made up 68.13% of all cases, mainly adrenal cysts (19.52%), pheochromocytoma (18.73%), benign adenoma (16.73%), and myelolipoma (7.17%). Malignant LATs accounted for 28.69% of cases, mainly including adrenocortical carcinoma (8.76%) and metastases (17.13%). Laparoscopic surgery was found to involve less trauma than open surgery. It was also safer and postoperative recovery was faster, but it had drawbacks and could not completely replace open surgery. CT features had obvious specificity for the diagnosis of benign and malignant tumors. For example, benign adenomas had a smaller pre-contrast (< 10 Hu) whereas malignant adrenal tumors had, on the contrary, higher attenuation. Regarding adrenal malignant carcinoma, adrenal primary malignant tumors showed a better prognosis than adrenal metastases (mean survival of 19.17 months vs 9.49 months). Primary adrenal cortical carcinoma without metastasis had a better prognosis than primary adrenal cortical carcinoma metastasis (mean survival of 23.71 months vs 12.75 months), and adrenal solitary metastasis had a better prognosis than general multiple metastatic carcinoma (mean survival of 14.95 months vs 5.17 months). CONCLUSION: LATs were more likely to be benign; however, they still had a high probability of being a malignant tumor. Understanding the clinicopathological characteristics of LATs can facilitate selection of more effective clinical treatment options.

New Method for Detecting the Suppressing Effect of Enzyme Activity by Aminopeptidase N Inhibitor.

Aminopeptidase N, also known as CD13, is a transmembrance protease with many functions. CD13 is involved in inflammatory diseases and cancers. A convenient and reliable laboratory test method for detecting the suppressing effects of enzyme activity would be useful for study of CD13 inhibitors. Porcine CD13 (pCD13) was traditionally considered an enzyme source but has significant practical disadvantages. pCD13 is not a human source, and the accuracy and reliability of experimental results are greatly reduced. In this study, a modified detection method with K562-CD13 monoclonal cells, a human-derived cell line, was established to detect the suppressing effects of enzyme activity by the CD13 inhibitor. In this method, K562-CD13 monoclonal cells were used as enzyme source and L-leucine p-nitroaniline hydrochloride as substrate. Using CD13 enzyme activity analyses, we found that the ability of the catalytic substrate was weaker in K562 cells than in the other cell lines, and K562-CD13 cells expressed significantly higher levels of CD13 enzyme activity than parental K562 cells. The enzyme activity of CD13 was detected with the new method after ubenimex treatment. The enzyme activity was significantly inhibited by ubenimex in a dose-dependent manner. In summary, this study proposes a sensitive, stable, and objective laboratory method for detecting the inhibitory effect of the CD13 inhibitor.