AND Logic-Gate-Based Dual-Locking Probe System for the Sensitive Detection of microRNA and APE1.

MicroRNA (miRNA) and apurinic/apyrimidinic endonuclease 1 (APE1) have been reported to be closely associated with cancers, making them potential crucial biomarkers and therapeutic targets. However, focusing on the detection of a single target is not conducive to the diagnosis and prognosis assessment of diseases. In this study, an AND logic-gate-based dual-locking hairpin-mediated catalytic hairpin assembly (DL-CHA) was developed for sensitive and specific detection of microRNA and APE1. By addition of a lock to each of the hairpins, with APE1 and microRNA serving as keys, fluorescence signals could only be detected in the presence of simultaneous stimulation by APE1 and miRNA-224. This indicated that the biosensor could operate as an AND logic gate. DL-CHA exhibited advantages such as a low background, rapid response, and high logic capability. Therefore, the biosensor serves as a novel approach to cancer diagnosis with significant potential applications.

CoS2-MoS2 Nanoflower Arrays for Efficient Hydrogen Evolution Reaction in the Universal pH Range.

To explore, highly active electrocatalysts are essential for water splitting materials. Polyoxometalates (POMs) have drawn interesting attention in recent years due to their abundant structure and unique electrocatalytic properties. In this study, by using a POM-based precursor Co2Mo10, novel bimetallic sulfide (CoS2-MoS2) nanocomposites are rationally designed and synthesized under hydrothermal conditions. The incorporation of Co2+ to the host electrocatalyst could effectively increase the exposure of active sites of MoS2. Compared to pure MoS2, the CoS2-MoS2 nanocomposite exhibited a perfect hydrogen evolution reaction (HER) ability, for it merely requires overpotentials of 120 and 153 mV for 10 mA cm-2 working current density toward the HER in 1 M KOH and 0.5 M H2SO4 electrolyte systems, respectively. Additionally, the nanocomposite exhibited outstanding chemical stability and long-term durability. This study presents a novel strategy that utilizes POMs to enrich the exposed edge sites of MoS2, resulting in the preparation of efficient electrocatalysts.

Ir Nanoparticles Supported on Oxygen-Deficient Vanadium Oxides Prepared by a Polyoxovanadate Precursor for Enhanced Electrocatalytic Hydrogen Evolution.

Developing highly active electrocatalysts is crucial for the application of electrocatalytic water splitting. In this study, we prepared vanadium oxide-graphene carbon nanocomposites (VxOy/C) with abundant defects using a carbon- and oxygen-rich hexavanadate derivative Na2[V6O7{(OCH2)3CCH3}4] as a precursor without the addition of an extra carbon source. Subsequently, the VxOy/C was used as a catalyst support to load a small amount of Ir, forming the Ir/VxOy/C nanoelectrocatalyst. This catalyst exhibited low hydrogen evolution overpotentials of only 18.90 and 13.46 mV at a working current density of 10 mA cm-2 in 1.0 M KOH and 0.5 M H2SO4 electrolyte systems, outperforming the commercial Pt/C catalysts. Additionally, the catalyst showed excellent chemical stability and long-term durability. This work provides a new strategy for the design and synthesis of highly active electrocatalysts for water splitting.

Efficient Hydrogen Production over Molybdenum Tungsten Bimetallic Oxide NF/PMonW12-n Catalyst on Nickel Foam.

Developing inexpensive, efficient, and stable catalysts is crucial for reducing the cost of electrolytic hydrogen production. Recently, polyoxometalates (POMs) have gained attention and widespread use due to their excellent electrocatalytic properties. This study designed and synthesized three composite materials, NF/PMonW12-n, by using phosphomolybdic-tungstic heteropolyacids as precursors to grow in situ on nickel foam via the hydrothermal process and subsequent calcination. Then, their catalytic performances are systematically investigated. This work demonstrates that the NF/PMonW12-n catalysts generate more low valent oxides under the synergistic effect of Mo and W, further enhancing activity for hydrogen evolution reaction (HER). Among these electrocatalysts, NF/PMo6W6 exhibits the perfect HER performance, η10 is only 74 mV. It also shows great stability during long-term electrolysis. The current study introduces a fresh approach for producing electrocatalysts that are both cost-effective and highly efficient.

Global research trends in cutaneous neurofibromas: A bibliometric analysis from 2003 to 2022.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a common inherited disorder characterized by cutaneous neurofibromas and other features. It is still a challenge in managing inoperable patients and the complex nature of the disease. Bibliometric analyses for cutaneous neurofibromas (cNF) could offer insights into impactful research and collaborations, guiding future efforts to improve patient care and outcomes. METHODS: We conducted a comprehensive literature search of the Web of Science Core Collection database for the period 2003-2022. Data processing and analysis were performed using bibliometric tools including VOSviewer, CiteSpace, and "Bibliometrix" package. Our analysis assessed the publication or collaboration of countries, institutions, authors, and journals, as well as the co-citation and burst of references and keywords. RESULTS: The analysis included 927 articles from 465 journals and 1402 institutions in 67 countries. Research on cNF has been increasing in recent years. The United States leads the field. Pierre Wolkenstein was the top author, while The University of Hamburg was the most productive institution. The American Journal of Medical Genetics Part A published the most articles in cNF. Co-citation analysis revealed major research topics and trends over time, showing growing interest in evaluating quality of life and genotype-phenotype correlation for cNF patients. Emerging topical MEK inhibitors show potential as a promising therapy. CONCLUSION: In conclusion, our bibliometric analysis of cNF research over the past two decades highlights the growing interest in this complex genetic disorder. Leading countries, authors, institutions, and journals have played significant roles in shaping the field. Notably, recent trends emphasize the importance of evaluating quality of life and genotype-phenotype correlations in cNF patients. Furthermore, the emergence of promising topical therapy marks an exciting development in the quest to improve patient care and outcomes for those affected by cNF, paving the way for future research and collaboration.

The correlation between the need for continuing care services, influencing factors, and social support and discharge readiness among discharged patients with pulmonary tuberculosis in China: A cross-sectional study.

OBJECTIVE: To understand the relationship between the need for continuing care services and influencing factors, social support, readiness for discharge among discharged pulmonary tuberculosis (PTB) patients. METHODS: A cross-sectional study was conducted among 170 patients from a database of discharged patients with PTB from September 2023 to January 2024. A demographic and disease characteristics questionnaire, continuing care services basic modality questionnaire, continuing care services need questionnaire, the Social Support Rating Scale (SSRS), and the Readiness for Hospital Discharge Scale (RHDS) were used for this investigation. Univariate analysis and multiple linear regression analysis were used to analyze the associated factors. RESULTS: The mean total score for the need for continuing care services among patients with PTB discharged from the hospital was (121.61 ± 22.98). The dimension with the highest score was health education guidance need. Compared to the the original hospital medical personnel, the primary source of care information after discharge was the local medical institutions was statistically significant and negatively correlated with continuing care service need (P = 0.005). Social support was positively associated with need for continuing care services (P = 0.042). CONCLUSION: Discharged PTB patients had a high degree of continuing care service need. Factors influencing the need for continuing care services are the primary source of care information after discharge was the local medical institutions, the social support. Medical staff need to provide targeted continuing care services based on relevant influencing factors to meet the discharge needs of patients.

Characteristics of white matter alterations along fibres in patients with bulimia nervosa: A combined voxelwise and tractography study.

Accumulating evidence supports the hypothesis that white matter (WM) abnormalities are involved in the pathophysiology of bulimia nervosa (BN); however, findings from in vivo neuroimaging studies have been inconsistent. We aimed to investigate the possible brain WM alterations, including WM volume and microstructure, in patients with BN. We recruited 43 BN patients and 31 healthy controls (HCs). All participants underwent structural and diffusion tensor imaging. Differences in WM volume and microstructure were evaluated using voxel-based morphometry, tract-based spatial statistics, and automated fibre quantification analysis. Compared with HCs, BN patients showed significantly decreased fractional anisotropy in the middle part of the corpus callosum (nodes 31-32) and increased mean diffusivity in the right cranial nerve V (CN V) (nodes 27-33 and nodes 55-88) and vertical occipital fasciculus (VOF) (nodes 58-85). Moreover, we found decreased axial diffusivity in the right inferior fronto-occipital fasciculus (node 67) and increased radial diffusivity in the CN V (nodes 22-34 and nodes 52-89) and left VOF (nodes 60-66 and nodes 81-85). Meanwhile, WM microstructural changes were correlated with patients' clinical manifestations. We did not find any significant differences in WM volume and the main WM fibre bundle properties between BN patients and HCs. Taken together, these findings provide that BN shows significant brain WM reorganization, but primarily in microstructure (part of WM fibre bundle), which is not sufficient to cause changes in WM volume. The automated fibre quantification analysis could be more sensitive to detect the subtle pathological changes in a point or segment of the WM fibre bundle.

Phase I dose escalation study and pilot efficacy analysis of LXI-15029, a novel mTOR dual inhibitor, in Chinese subjects with advanced malignant solid tumors.

BACKGROUND: The mammalian target of rapamycin (mTOR) kinase, a central component of the PI3K/AKT/mTOR pathway, plays a critical role in tumor biology as an attractive therapeutic target. We conducted this first-in-human study to investigate the safety, pharmacokinetics (PK), and pilot efficacy of LXI-15029, an mTORC1/2 dual inhibitor, in Chinese patients with advanced malignant solid tumors. METHODS: Eligible patients with advanced, unresectable malignant solid tumors after failure of routine therapy or with no standard treatment were enrolled to receive ascending doses (10, 20, 40, 60, 80, 110, and 150 mg) of oral LXI-15029 twice daily (BID) (3 + 3 dose-escalation pattern) until disease progression or intolerable adverse events (AEs). The primary endpoints were safety and tolerability. RESULTS: Between June 2017 and July 2021, a total of 24 patients were enrolled. LXI-15029 was well tolerated at all doses. Only one dose-limiting toxicity (grade 3 increased alanine aminotransferase) occurred in the 150 mg group, and the maximum tolerated dose was 110 mg BID. The most common treatment-related AEs were leukocytopenia (41.7%), increased alanine aminotransferase (20.8%), increased aspartate aminotransferase (20.8%), prolonged electrocardiogram QT interval (20.8%), and hypertriglyceridemia (20.8%). No other serious treatment-related AEs were reported. LXI-15029 was absorbed rapidly after oral administration. The increases in the peak concentration and the area under the curve were greater than dose proportionality over the dose range. Eight patients had stable disease. The disease control rate was 40.0% (8/20; 95% CI 21.7-60.6). In evaluable patients, the median progression-free survival was 29 days (range 29-141). CONCLUSIONS: LXI-15029 demonstrated reasonable safety and tolerability profiles and encouraging preliminary antitumor activity in Chinese patients with advanced malignant solid tumors, which warranted further validation in phase II trials. TRIAL REGISTRATION: NCT03125746(24/04/2017), http://ClinicalTrials.gov/show/NCT03125746.

ORC6, a novel prognostic biomarker, correlates with T regulatory cell infiltration in prostate adenocarcinoma: a pan-cancer analysis.

BACKGROUND: The origin recognition complex (ORC), a six-subunit DNA-binding complex, participates in DNA replication in cancer cells. Specifically in prostate cancers, ORC participates the androgen receptor (AR) regulated genomic amplification and tumor proliferation throughout the entire cell cycle. Of note, ORC6, the smallest subunit of ORC, has been reported to be dysregulated in some types of cancers (including prostate cancer), however, its prognostic and immunological significances remain yet to be elucidated. METHODS: In the current study, we comprehensively investigated the potential prognostic and immunological role of ORC6 in 33 human tumors using multiple databases, such as TCGA, Genotype-Tissue Expression, CCLE, UCSC Xena, cBioPortal, Human Protein Atlas, GeneCards, STRING, MSigDB, TISIDB, and TIMER2 databases. RESULTS: ORC6 expression was significantly upregulated in 29 types of cancers compared to the corresponding normal adjacent tissues. ORC6 overexpression correlated with higher stage and worse prognostic outcomes in most cancer types analyzed. Additionally, ORC6 was involved in the cell cycle pathway, DNA replication, and mismatch repair pathways in most tumor types. A negative correlation was observed between the tumor endothelial cell infiltration and ORC6 expression in almost all tumors, whereas the immune infiltration of T regulatory cell was noted to be statistically positively correlated with the expression of ORC6 in prostate cancer tissues. Furthermore, in most tumor types, immunosuppression-related genes, especially TGFBR1 and PD-L1 (CD274), exhibited a specific correlation with the expression of ORC6. CONCLUSIONS: This comprehensive pan-cancer analysis revealed that ORC6 expression serves as a prognostic biomarker and that ORC6 is involved in the regulation of various biological pathways, the tumor microenvironment, and the immunosuppression status in several human cancers, suggesting its potential diagnostic, prognostic, and therapeutic value in pan-cancer, especially in prostate adenocarcinoma.

The role of functional and structural properties of the nucleus accumbens subregions in eating behavior regulation of bulimia nervosa.

OBJECTIVE: Although studies have demonstrated the involvement of the nucleus accumbens (NAc) in the neurobiology of eating disorders, its alterations in bulimia nervosa (BN) remain largely unknown. This study investigated the structural and functional properties of NAc in patients with BN. METHOD: Based on the resting-state functional MRI and high-resolution anatomical T1-weighted imaging data acquired from 43 right-handed BN patients and 40 sex-, age- and education-matched right-handed healthy controls (HCs), the group differences in gray matter volume (GMV) and fractional amplitude of low-frequency fluctuation (fALFF) in slow-4 and -5 bands and functional connectivity (FC) of NAc subregions (core and shell) were compared. The relationships between MRI and clinical data were explored in the BN group. RESULTS: Compared with HCs, BN patients showed preserved GMV, decreased fALFF in slow-5 band of the left NAc core and shell, decreased FC between left NAc core and right caudate, and increased FC between all NAc subregions and frontal regions, between all NAc subregions (except the right NAc core) and the supramarginal gyrus (SMG), and between right NAc shell and left middle temporal gyrus. FC between the NAc and SMG was correlated with emotional eating behaviors. DISCUSSION: Our study revealed preserved GMV, local neuronal activity reduction and functional network reorganization of the NAc in BN. The functional network reorganization of the NAc mainly occurred in the frontal cortex and was correlated with emotional eating behavior. These findings may provide novel insights into the BN using NAc as an entry point. PUBLIC SIGNIFICANCE: Although studies have demonstrated the involvement of the nucleus accumbens (NAc) in the neurobiology of eating disorders, its alterations in bulimia nervosa (BN) remain largely unknown. We used a multimodal MRI technique to systematically investigate structural and functional alterations in NAc subregions of BN patients and explored the associations between such alterations and maladaptive eating behaviors, hoping to provide novel insights into BN.

Dynamics of antibiotic resistance genes and bacterial community during pig manure, kitchen waste, and sewage sludge composting.

Organic solid wastes (OSWs) are important reservoirs for antibiotic resistance genes (ARGs). Aerobic composting transforms OSWs into fertilizers. In this study, we investigated ARGs dynamics and their driving mechanisms in three OSW composts: pig manure (PM), kitchen waste (KC), and sewage sludge (SG). The dominant ARGs were different in each OSW, namely tetracycline, aminoglycoside, and macrolide resistance (PM); tetracyclines and aminoglycosides (KC); and sulfonamides (SG). ARGs abundance decreased in PM (71%) but increased in KC (5.9-fold) and SG (1.3-fold). Interestingly, the ARGs abundance was generally similar in all final composts, which was contributed to the similar bacterial community in final composts. In particular, sulfonamide and ß-lactam resistant genes removed (100%) in PM, while sulfonamide in KC (38-fold) and tetracycline in SG (5-fold) increased the most. Additionally, ARGs abundance rebounded during the maturation period in all treatments. Firmicutes, Proteobacteria, and Actinobacteria were the main ARGs hosts. Several persistent and high-risk genes included tetW, aadA, aadE, tetX, strB, tetA, mefA, intl1, and intl2. The structural equation models showed ARGs removal was mainly affected by physicochemical parameters and bacterial communities in PM, the ARGs enrichment in KC composting correlated with increased mobile genetic elements (MGEs). In general, thermophilic aerobic composting can inhibit the vertical gene transfer (VGT) of pig manure and horizontal gene transfer (HGT) of sludge, but it increases the HGT of kitchen waste, resulting in a dramatic increase of ARGs in KC compost. More attention should be paid to the ARGs risk of kitchen waste composting.

Uncovering neural pathways underlying bulimia nervosa: resting-state neural connectivity disruptions correlate with maladaptive eating behaviors.

PURPOSE: Bulimia nervosa (BN) is characterized by recurrent binge-eating episodes and inappropriate compensatory behaviors. This study investigated alterations in resting-state surface-based neural activity in BN patients and explored correlations between brain activity and eating behavior. METHODS: A total of 26 BN patients and 28 healthy controls were enrolled. Indirect measurement of cerebral cortical activity and functional connectivity (FC) analyses were performed in Surfstat. A principal component analysis (PCA) model was used to capture the commonalities within the behavioral questionnaires from the BN group. RESULTS: Compared with the healthy control group, the BN group showed decreased surface-based two-dimensional regional homogeneity in the right superior parietal lobule (SPL). Additionally, the BN group showed decreased FC between the right SPL and the bilateral lingual gyrus and increased FC between the right SPL and the left caudate nucleus and right putamen. In the FC-behavior association analysis, the second principal component (PC2) was negatively correlated with FC between the right SPL and the left caudate nucleus. The third principal component (PC3) was negatively correlated with FC between the right SPL and the left lingual gyrus and positively correlated with FC between the right SPL and the right lingual gyrus. CONCLUSION: We revealed that the right SPL undergoes reorganization with respect to specific brain regions at the whole-brain level in BN. In addition, our results suggest a correlation between brain reorganization and maladaptive eating behavior. These findings may provide useful information to better understand the neural mechanisms of BN. LEVEL OF EVIDENCE: V, descriptive study.

The lipoxygenase gene OsRCI-1 is involved in the biosynthesis of herbivore-induced JAs and regulates plant defense and growth in rice.

The pathway mediated by jasmonic acid (JA), biosynthesized via 13-lipoxygenases (LOX), plays a central role in both plant development and defense. In rice, there are at least fourteen 13-LOXs. Yet, only two 13-LOXs have been known to be involved in the biosynthesis of JA and plant defenses in rice. Here we cloned a chloroplast-localized 13-LOX gene from rice, OsRCI-1, whose transcripts were upregulated following infestation by brown planthopper (BPH, Nilaparvata lugens), one of the most important pests in rice. Overexpression of OsRCI-1 (oeRCI lines) increased levels of BPH-induced JA, jasmonate-isoleucine, trypsin protease inhibitors and three volatile compounds, 2-heptanone, 2-heptanol and α-thujene. BPHs showed a decreased colonization, fecundity and mass, and developed slowly on oeRCI plants compared with wild-type (WT) plants. Moreover, BPH-infested oeRCI plants were more attractive to the egg parasitoid of BPH, Anagrus nilaparvatae than equally treated WT plants. The decreased attractiveness to BPH and enhanced attractiveness to the parasitoid of oeRCI plants correlated with higher levels of BPH-induced 2-heptanone and 2-heptanol, and 2-heptanone, respectively. Compared with oeRCI plants, WT plants had higher plant height and 1000-grain weight. These results indicate that OsRCI-1 is involved in herbivore-induced JA bursts and plays a role in plant defense and growth.

CTSB Knockdown Inhibits Proliferation and Tumorigenesis in HL-60 Cells.

Background: Cathepsin B (CTSB) was well documented in solid tumors, up-regulated of CTSB expression is linked with progression of tumors. However, the study of CTSB in adult leukemia has not been reported. Methods: Total RNA was isolated from PBMC (peripheral blood mononuclear cell) of AML patients and healthy donors. qRT-PCR was performed to detect the expression of CTSB. The association of CTSB expression with the patients' overall survival (OS) and disease-free survival (DFS) were analyzed. Stable HL-60 CTSB-shRNA cell lines were established by retrovirus infection and puromycin selection. Cell proliferation was detected by CCK-8 analysis. Tumorigenesis ability was analyzed by soft agar and xenograft nude mice model. Western blot was performed to detect the expression of CTSB and the proteins of cell signaling pathway. Results: The mRNA expression level of CTSB was up-regulated in AML patients compared to healthy control (p<0.001), and CTSB expression was significantly higher in M1, M2, M4 and M5 AML samples than healthy control. The CTSB expression in AML was associated with WBC count (p=0.037). Patients with high CTSB expression had a relatively poor OS (p=0.007) and a shorter DFS (p=0.018). Moreover, the expression level of CTSB may act as an independent prognostic factor for both OS (p=0.011) and DFS (p=0.004). Knockdown CTSB expression in HL-60 cells could inhibit the cells' proliferation and tumorigeneses in vitro and in vivo. Further study showed knockdown CTSB expression in HL-60 cells could inactive the AKT signaling pathway. Conclusions: CTSB mRNA was upregulated in AML patients. CTSB overexpression was correlated with poor prognosis and may serve as an independent prognostic factor for both OS and DFS in AML patients. Knockdown CTSB expression in HL-60 cells could inhibit the cells' proliferation and tumorigenesis. The underlying mechanism may be the inhibition of the AKT signaling pathway.

Virtual reality for limb motor function, balance, gait, cognition and daily function of stroke patients: A systematic review and meta-analysis.

AIMS: To explore the beneficial effects of virtual reality (VR) interventions on upper- and lower-limb motor function, balance, gait, cognition and daily function outcomes in stroke patients. DESIGN: A systematic review and meta-analysis of randomized controlled trials. DATA SOURCES: English databases (PubMed, EMBASE, the Cochrane Library, CINAHL, Web of Science, Physiotherapy Evidence Database, ProQuest Dissertations and Theses) and Chinese databases (Chinese BioMedical Literature Service System, WANFANG, CNKI) and the Clinical Trial Registry Platform were systematically searched from inception until December 2019. Additionally, reference lists of the included studies were manually searched. REVIEW METHODS: The methodological quality of studies was scored with the Cochrane 'risk-of-bias tool' and PEDro scale from the Physiotherapy Evidence Database by two independent evaluators. RESULTS: In total, 87 studies with 3540 participants were included. Stroke patients receiving VR interventions showed significant improvements in Fugl-Meyer assessment of Upper Extremity, Action Research Arm Test, Wolf Motor Function Test, Fugl-Meyer Assessment of Lower Extremity, Functional Ambulation Classification, Berg Balance Scale, Time Up and Go, Velocity, Cadence, Modified Barthel Index and Functional Independence Measure. However, differences between VR intervention and traditional rehabilitation groups were not significant for Box-Block Test, 10 m Walk Test, Auditory Continuous Performance Test, Mini-Mental State Examination and Visual Continuous Performance Test. CONCLUSION: This review suggests that VR interventions effectively improve upper- and lower-limb motor function, balance, gait and daily function of stroke patients, but have no benefits on cognition. IMPACT: This review identified the positive effects of VR-assisted rehabilitation on upper- and lower-limb motor function, balance, gait and daily function of stroke patients. And, we verified the duration of VR intervention affects some health benefits. The benefit of VR on cognitive function requires further investigation through large-scale multicentre RCTs.

Identification and Analysis of the AP2 Subfamily Transcription Factors in the Pecan (Carya illinoinensis).

The AP2 transcriptional factors (TFs) belong to the APETALA2/ ethylene-responsive factor (AP2/ERF) superfamily and regulate various biological processes of plant growth and development, as well as response to biotic and abiotic stresses. However, genome-wide research on the AP2 subfamily TFs in the pecan (Carya illinoinensis) is rarely reported. In this paper, we identify 30 AP2 subfamily genes from pecans through a genome-wide search, and they were unevenly distributed on the pecan chromosomes. Then, a phylogenetic tree, gene structure and conserved motifs were further analyzed. The 30 AP2 genes were divided into euAP2, euANT and basalANT three clades. Moreover, the cis-acting elements analysis showed many light responsive elements, plant hormone-responsive elements and abiotic stress responsive elements are found in CiAP2 promoters. Furthermore, a qPCR analysis showed that genes clustered together usually shared similar expression patterns in euAP2 and basalANT clades, while the expression pattern in the euANT clade varied greatly. In developing pecan fruits, CiAP2-5, CiANT1 and CiANT2 shared similar expression patterns, and their expression levels decreased with fruit development. CiANT5 displayed the highest expression levels in developing fruits. The subcellular localization and transcriptional activation activity assay demonstrated that CiANT5 is located in the nucleus and functions as a transcription factor with transcriptional activation activity. These results help to comprehensively understand the pecan AP2 subfamily TFs and lay the foundation for further functional research on pecan AP2 family genes.

[High-fat diet induces metabolic syndrome in mice and its influence on intestinal development, liver function and intestinal microbiota].

OBJECTIVE: To evaluate the possibility of high-fat diet to induce metabolic syndrome and to alter intestinal development, liver function and intestinal microbiotaof C57 BL/6 J mice. METHODS: Total 40 of male C57 BL/6 J aged 3 weeks old were randomly divided into two groups: control group and high-fat diet group. After one week of adaptive feeding, the tested mice in high-fat diet group were fed with high-fat diet for 20 weeks, while those in control group were fed with ordinary diet. During the intervention, the body weight of the tested mice was measured weekly and fasting blood glucose(FBG) was measured monthly. Before the end of the experiment, the oral glucose tolerance test(OGTT) of the tested mice was conducted and the fecal 16 S rRNA sequencing was used to profile fecal microbiota of the test mice. Real-time qPCR was used to analyze the concentration of fecal bifidobacteria. Viscera coefficient of liver, spleen and pancreas, visceral fat-body ratio and intestinal length were measured. The indexes of liver function and the levels of serum lipids, leptin and adiponectin were also measured. Liver inflammation and fat infiltration were observed by anatomical pathological analysis. RESULTS: After intervention of high fat diet, the body weight, FBG, oral glucose tolerance, the fat-body ratio, the levels of serum lipids, leptin and adiponectin of mice were significantly increased(P<0. 05). The inflammatory state of liver and the degree of fat infiltration increased. The length of intestine decreased(P<0. 05). The concentration of Bifidobacterium decreased(P<0. 05), however, the concentration of B. bifidum and B. angulatum increased(P<0. 05). The ACE, Chao1, Shannon and Simpson indexes of the high-fat diet were significantly lower than that of the control group(P<0. 05). Firmicutes, Proteobacteria and Deferribacteres were found significantly more in high-fat diet group(P<0. 05), while Bacteroidetes and Verrucomicrobia were apparently more in control group(P<0. 05). CONCLUSION: High-fat diet could induce the metabolic syndrome in tested C57 BL/6 J, and lead to the damage of intestinal development, abnormality of liver tissue and its function, decrease diversity of intestinal microbiota, and the transformation of intestinal microbiota community to obesity type.

Therapeutic Mechanism of Macrophage Inflammatory Protein 1 α Neutralizing Antibody (CCL3) in Clostridium difficile Infection in Mice.

BACKGROUND: Clostridium difficile infection (CDI) causes diarrhea and colitis. We aimed to find a common pathogenic pathway in CDI among humans and mice by comparing toxin-mediated effects in human and mouse colonic tissues. METHOD: Using multiplex enzyme-linked immunosorbent assay, we determined the cytokine secretion of toxin A- and B-treated human and mouse colonic explants. RESULTS: Toxin A and toxin B exposure to fresh human and mouse colonic explants caused different patterns of cytokine secretion. Toxin A induced macrophage inflammatory protein (MIP) 1α secretion in both human and mouse explants. Toxin A reduced the expression of chloride anion exchanger SLC26A3 expression in mouse colonic explants and human colonic epithelial cells. Patients with CDI had increased colonic MIP-1 α expression and reduced colonic SLC26A3 (solute carrier family 26, member 3) compared with controls. Anti-MIP-1 α neutralizing antibody prevented death, ameliorated colonic injury, reduced colonic interleukin 1ß (IL-1ß) messenger RNA expression, and restored colonic SLC26a3 expression in C. difficile-infected mice. The anti-MIP-1 α neutralizing antibody prevented CDI recurrence. SLC26a3 inhibition augmented colonic IL-1 ß messenger RNA expression and abolished the protective effect of anti-MIP-1 α neutralizing antibody in mice with CDI. CONCLUSION: MIP-1 α is a common toxin A-dependent chemokine in human and mouse colon. MIP-1 α mediates detrimental effects by reducing SLC26a3 and enhancing IL-1 ß expression in the colon.

FLAD1 is up-regulated in Gastric Cancer and is a potential prediction of prognosis.

Background: Gastric cancer (GC) is a common malignancy throughout the world. Biomarkers for prognosis and risk evaluation of GC are rapidly discovered. We investigated the prognostic role of FLAD1, an important protein-coding gene that affects cell cycle and survival. Methods: The expression of FLAD1 at mRNA levels in GC tumor tissues and normal tissues was mined and analyzed in Oncomine database and verified in 10 pairs of GS tissues and their adjacent normal tissues in our center by RT qPCR. The FLAD1 protein expression were detected in 106 paraffin-embedded GC tissues by immunohistochemistry (IHC). Statistical analyses were applied to evaluate the clinical significance of FLAD1. The prognostic value of FLAD1 mRNA expression was also analyzed using the Kaplan-Meier plotter (www.kmplot.com). Results: Statistics obtained from online database suggested FLAD1 mRNA was overexpressed in GC tissues. The results were further validated in 10 pairs of GS tissues and adjacent normal tissues in our center (p=0.021). IHC and survival analysis of GC samples from 106 patients showed FLAD1 was overexpressed in 63/106 (59.4%) patients and was associated to higher TNM stage (p=0.026). Multivariate analysis revealed FLAD1 was an independent prognostic factor for GC (p < 0.001). Furthermore, FLAD1 mRNA was associated to unfavorable overall survival (OS), first progression (FP), and post-progression survival (PPS) of GC (p<0.001). Conclusion: FLAD1 in GC is overexpressed at both mRNA and protein level and could be a potential biomarker for GC prognosis.

Expression Profile and Prognostic Values of Mini-Chromosome Maintenance Families (MCMs) in Breast Cancer.

BACKGROUND Mini-chromosome maintenance families (MCMs) were considered the key factors for DNA replication initiation. Emerging evidences indicate that MCM2-7 (MCMs) are highly expressed in tissues from various malignant tumors. However, little is known about the clinical values of MCMs in breast cancer. MATERIAL AND METHODS In our study, a comprehensive bioinformatics analysis was performed to investigate expression patterns, potential functions, and prognostic values of MCMs in breast cancer, through ONCOMINE, bc-GenExMiner v4.1, Kaplan-Meier Plotter, cBioPortal and GeneMANIA databases. RESULTS We found that mRNA levels of MCMs were significantly elevated in breast cancer, especially in fast-growing and spreading tumor subtypes. These over-expressed MCMs predicted worse prognosis for breast cancer patients with shorter relapse-free survival (RFS) and overall survival. Among these six factors, high expression of MCM2/4/5/7 significantly reduced the RFS for patients with Luminal-A or B breast cancer and elevated MCM6/7 indicated shorter RFS for patients with basal-like or HER2-positive breast cancer. We also found that genomic alteration of MCMs was frequently found in breast cancer and the most common alteration was mRNA upregulation and amplification. Furthermore, MCMs were highly correlated with CDC45, CDC7, TIMELESS, ORC6, MCM10, ORC5, ORC4 and ORC3, mainly functioning to control the DNA replication initiation and genome stability. CONCLUSIONS These results suggest that MCMs are attractive prognostic biomarkers for breast cancer. Our study also provides useful clinical information about the potential of MCMs as therapeutic targets.