The safety and feasibility of the simultaneous resection of primary colorectal cancer (CRC) and synchronous colorectal liver metastases (SCRLM) have been demonstrated in some studies. Combined ...resection is expected to be the optimal strategy for patients with CRC and SCRLM. However, traditional laparotomy is traumatic, and the treatment outcome of minimally invasive surgery (MIS) is still obscure.
To compare the treatment outcomes of MIS and open surgery (OS) for the simultaneous resection of CRC and SCRLM.
A systematic search through December 22, 2018 was conducted in electronic databases (PubMed, EMBASE, Web of Science, and Cochrane Library). All studies comparing the clinical outcomes of MIS and OS for patients with CRC and SCRLM were included by eligibility criteria. The meta-analysis was performed using Review Manager Software. The quality of the pooled study was assessed using the Newcastle-Ottawa scale. The publication bias was evaluated by a funnel plot and the Begg's and Egger's tests. Fixed- and random-effects models were applied according to heterogeneity.
Ten retrospective cohort studies involving 502 patients (216 patients in the MIS group and 286 patients in the OS group) were included in this study. MIS was associated with less intraoperative blood loss weighted mean difference (WMD) = -130.09, 95% confidence interval (CI): -210.95 to -49.23,
= 0.002 and blood transfusion odds ratio (OR) = 0.53, 95%CI: 0.29 to 0.95,
= 0.03, faster recovery of intestinal function (WMD = -0.88 d, 95%CI: -1.58 to -0.19,
= 0.01) and diet (WMD = -1.54 d, 95%CI: -2.30 to -0.78,
0.0001), shorter length of postoperative hospital stay (WMD = -4.06 d, 95%CI: -5.95 to -2.18,
0.0001), and lower rates of surgical complications (OR = 0.60, 95%CI: 0.37 to 0.99,
= 0.04). However, the operation time, rates and severity of overall complications, and rates of general complications showed no significant differences between the MIS and OS groups. Moreover, the overall survival and disease-free survival after MIS were equivalent to those after OS.
Considering the studies included in this meta-analysis, MIS is a safe and effective alternative technique for the simultaneous resection of CRC and SCRLM. Compared with OS, MIS has less intraoperative blood loss and blood transfusion and quicker postoperative recovery. Furthermore, the two groups show equivalent long-term outcomes.
Dear Editor, Animals carrying exogenous genes integrated at specific genomic loci are versatile tools for biological research 1. Zebrafish （Danio rerio）, an emerging vertebrate animal model, is ...widely used in studies on genetics, developmental biology and neurobiology. Although loss-of-function genomic editing for zebrafish has been well developed 2-5, lack of feasible methods for inserting a large exogenous DNA sequence into the zebrafish genome is becoming a bottleneck for zebrafish-relevant research.
The grain boundary (GB) migration and dislocation movement are the basic mechanisms of deformation and strengthening of alloys. The migration of circular and asymmetric tilt GB initiated from the ...dislocation movement during tensile deformation was investigated by phase-field crystal simulation. It is shown that the migration of circular GB is performed by dislocation slipping, accompanying by the rotation and tensile deformation of the circular grain. The dislocation dissociation and slipping realize the migration of low-angle asymmetric tilt GB. Additionally, the dislocation dissociation generates new grains with different orientations, then the new grains merge with the annihilation of dislocations. For high-angle asymmetric tilt GB, the migration mechanism is dislocation emission and slipping. The generation or merging of new grains reduces the misorientation of grains for low-angle asymmetric tilt GB. The formation of new grains at low-angle asymmetric tilt GB is caused by the dislocations dissociation, while the emission of dislocations generates the new grains in high-angle asymmetric tilt GB. The studies reveal the mechanisms of GB migration and grains reproduction by the dislocation slipping and reactions under the tensile deformation at the atomic scale.
The lack of reliable drugs is a therapeutic challenge of advanced breast cancers (ABCs). Resveratrol (Res) exerts inhibitory effects on breast cancer cell lines and animal models, while its efficacy ...against individual breast cancer cases remains unknown. This study aims to use ABC‐derived organoids (ABCOs) as the ex vivo therapeutic platform to clarify the effectiveness of resveratrol against different ABC subtypes. Immunohistochemical staining confirmed that the ABCOs maintained their original tumors' ER, PR, HER2, and Ki67 expression patterns. ABCO proliferation and viability tests showed >50% cell death rates in 79.2% (19/24) of Res‐treated, 28.6% (2/7) fulvestrant‐treated, 66.7% (4/6) paclitaxel‐treated, and 66.7% (6/9) gemcitabine‐treated ABCOs. pSTAT3 nuclear translocation was more frequent in Res‐sensitive (17/19; 89.47%) than that (1/5; 20%) of Res‐insensitive ABCOs, which were suppressed upon Res treatment. Statistical analysis revealed a close correlation of STAT3 activation with the efficacy of Res, but not related to tumor receptor expression patterns (ER, PR, HER2) and pathological classification. We demonstrate for the first time the higher efficacy and broader spectrum of Res against different subtypes of ABCOs in comparison with that of conventional antibreast cancer drugs, providing an alternative approach for better management of ABCs.
Mycobacterial arabinogalactan (AG) is an essential cell wall component of mycobacteria and a frequent structural and bio‐synthetical target for anti‐tuberculosis (TB) drug development. Here, we ...report that mycobacterial AG is recognized by galectin‐9 and exacerbates mycobacterial infection. Administration of AG‐specific aptamers inhibits cellular infiltration caused by Mycobacterium tuberculosis (Mtb) or Mycobacterium bovis BCG, and moderately increases survival of Mtb‐infected mice or Mycobacterium marinum‐infected zebrafish. AG interacts with carbohydrate recognition domain (CRD) 2 of galectin‐9 with high affinity, and galectin‐9 associates with transforming growth factor β‐activated kinase 1 (TAK1) via CRD2 to trigger subsequent activation of extracellular signal‐regulated kinase (ERK) as well as induction of the expression of matrix metalloproteinases (MMPs). Moreover, deletion of galectin‐9 or inhibition of MMPs blocks AG‐induced pathological impairments in the lung, and the AG‐galectin‐9 axis aggravates the process of Mtb infection in mice. These results demonstrate that AG is an important virulence factor of mycobacteria and galectin‐9 is a novel receptor for Mtb and other mycobacteria, paving the way for the development of novel effective TB immune modulators.
SYNOPSIS
Arabinogalactan is a virulence factor of mycobacteria. Binding of galectin‐9 to mycobacterial arabinogalactan triggers matrix metalloproteinases via TAK1‐ERK signaling, which promotes mycobacterial infection and increases lung injury.
Arabinogalactan exacerbates mycobacterial infection by causing lung injury.
AG‐specific aptamers inhibit cellular mycobacterium infiltration and increase survival of infected mice or fish.
Galectin‐9 is a receptor for mycobacterial arabinogalactan and activates the TAK1‐ ERK‐MMP signaling axis.
The Arabinogalactan‐galectin‐9 interface may be exploited for the design of new host‐directed therapies.
Arabinogalactan is a virulence factor of mycobacteria. Binding of galectin‐9 to mycobacterial arabinogalactan triggers matrix metalloproteinases via TAK1‐ERK signaling, which promotes mycobacterial infection and increases lung injury.
ZnO nanowires (ZnO-NWs) were adhesively grown on multiwalled carbon nanotubes (MWCNTs) arrays by a hydrothermal process. Electrochemical properties of the electrode based on the ZnO-NWs/MWCNTs ...nanocomposite were investigated by electrochemical impedance spectroscopy and cyclic voltammetry. The photoelectrochemical responses of the ZnO-NWs/MWCNTs nanocomposite electrode were further studied by linear sweep voltammetry and amperometry under sunlight or UV light irradiation. Compared with pure ZnO-NWs on tantalum substrate, the charge transfer rate of the ZnO-NWs/MWCNTs nanocomposite was remarkably increased because of the MWCNTs. A Mott−Schottky plot displayed a high donor density of 3.9 × 1019 cm−3, a flat band potential of −0.8 V, and a space charge layer of 7 nm. In addition, the ZnO-NWs/MWCNTs nanocomposite yielded higher photocurrent than pure ZnO-NWs. The decay constant of the ZnO-NWs/MWCNTs nanocomposite was also lower than that of its pure counterpart. The recombination of photoinduced electron−hole pairs in the ZnO-NWs/MWCNTs heterojunction was hindered, thus enhancing the photoelectrical conversion efficiency. The heterojunction of ZnO-NWs/MWCNTs provides potential applications in the field of photocatalysis and photoelectrical devices.
Antibiotic resistance is one of the biggest threats to public health, and new antibacterial agents hence are in an urgent need to combat infectious diseases caused by multidrug-resistant (MDR) ...pathogens. Utilizing dimerization strategy, we rationally designed and efficiently synthesized a new series of small molecule dimeric lysine alkylamides as mimics of AMPs. Evaluation of these mimics against a panel of Gram-positive and Gram-negative bacteria including MDR strains was performed, and a broad-spectrum and potent compound 3d was identified. This compound displayed high specificity toward bacteria over mammalian cell. Time–kill kinetics and mechanistic studies suggest that compound 3d quickly eliminated bacteria in a bactericidal mode by disrupting bacterial cell membrane. In addition, lead compound 3d could inhibit biofilm formation and did not develop drug resistance in S. aureus and E. coli over 14 passages. These results suggested that dimeric lysine nonylamide has immense potential as a new type of novel small molecular agent to combat antibiotic resistance.
An efficient and stereoselective one-pot, two-step tandem α-arylation of glycals from readily available aryl amines via stable diazonium salts has been developed. Moreover, the stereoselective ...preparation of the challenging β-C-glycosyl arenes by the anomerization of α-C-glycosides using HBF4 is also described. This protocol has a broad substrate scope and a wide functional-group tolerance. It can be used for the gram-scale preparation of 3-oxo-C-glycosides, which are versatile substrates for the preparation of many biologically important C-glycosides.
O-GlcNAcylation of carbohydrate-responsive element-binding protein (ChREBP) is believed as an important modulator of ChREBP activities, however little direct evidence of O-GlcNAcylation on ChREBP and ...no exact O-GlcNAcylation sites have been reported so far. Here, we validate O-GlcNAcylation on ChREBP in cell-free coupled transcription/translation system and in cells by chemoenzymatic and metabolic labeling, respectively. Moreover, for the first time, we identify O-GlcNAcylation on Ser614 in the C-terminus of ChREBP by mass spectrometry and validate two important sites, Thr517 and Ser839 for O-GlcNAcylation and their function via molecular and chemical biological method. Under high glucose conditions, Ser514 phosphorylation enhances ChREBP O-GlcNAcylation, maintaining the transcriptional activity of ChREBP; Ser839 O-GlcNAcylation is essential for Mlx-heterodimerization and DNA-binding activity enhancement, consequently inducing transcriptional activity. Ser839 O-GlcNAcylation is also crucial for ChREBP nuclear export partially by strengthening interactions with CRM1 and 14-3-3. This work is a detailed study of ChREBP O-GlcNAcylation and highlights the biological consequences of the site-specific O-GlcNAcylation dynamics of ChREBP.
Cerebral ischemia-reperfusion injury (IRI) is a common clinical pathological process, and it is a key step in causing further ischemic organ damage. The mechanism of cerebral IRI is still not fully ...understood, leading to a lack of effective treatment. It has been demonstrated that circular RNAs (circRNAs) can act as miRNA sponges and play an important role in regulating gene expression through a circRNA-miRNA-gene pathway. The specific role of circRNAs in the pathogenesis of cerebral IRI, however, is still unclear. Thus, in the present study, we investigated circRNA expression differences in HT22 cells with oxygen–glucose deprivation/reoxygenation (OGD/R) versus normal controls. The results from circRNA microarrays revealed that 15 circRNAs were significantly altered in the OGD/R model (p < 0.05) compared with the control group. Among them, 3 were significantly up-regulated, and the other 12 were down-regulated. Furthermore, the up-regulated expression of mmu-circRNA-015947 was verified using quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatics analysis revealed that up-regulated expression of mmu-circRNA-015947 could interact with miRNAs (mmu-miR-188-3p, mmu-miR-329-5p, mmu-miR-3057-3p, mmu-miR-5098 and mmu-miR-683) and thereby enhance target gene expression. KEGG pathway analysis predicted that mmu-circRNA-015947 may participate in apoptosis-related, metabolism-related and immune-related pathways, which are known to be involved in the pathogenesis of IRI. This research suggests that the overlapping expression of mmu-circRNA-015947 might be involved in the process of cerebral IRI and presents a novel molecular target for clinical therapy.
•CircRNA microarrays revealed that 15 circRNAs were significantly altered in the OGD/R model compared with the control group.•The up-regulated expression of mmu-circRNA-015947 was verified using qRT-PCR.•Bioinformatics analysis revealed that mmu-circRNA-015947 could interact with microRNAs and enhance target gene expression.•KEGG pathway analysis predicted that mmu-circRNA-015947 may participate in several pathways related to cerebral IRI.
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