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Skovbjerg Lundsgaard posted an update 6 months, 4 weeks ago
In the past few years, contact maps deep machine learning was introduced to the 3D structure prediction process, adding more information and increasing the accuracy of models significantly. In this review, we will take the reader in a journey of exploration from the beginnings to the most recent turnabouts, which have revolutionized the field of homology modeling. Moreover, we discuss the new trends emerging in this rapidly growing field.Despite improvements in our understanding of the biology behind triple-negative breast cancer (TNBC), it remains a devastating disease due to lack of an effective targeted therapy. Inhibiting Wnt signaling is a promising strategy to combat TNBC because Wnt signaling drives TNBC progression, chemoresistance, and stemness. However, Wnt inhibition can lead to upregulation of autophagy, which confers therapeutic resistance. This provides an opportunity for combination therapy, as autophagy inhibitors applied concurrently with Wnt inhibitors could increase treatment efficacy. DJ4 Here, we applied the autophagy inhibitor chloroquine (CQ) to TNBC cells in combination with Frizzled7 antibody-coated nanoshells (FZD7-NS) that suppress Wnt signaling by blocking Wnt ligand/FZD7 receptor interactions, and evaluated this dual treatment in vitro. We found that FZD7-NS can inhibit Axin2 and CyclinD1, two targets of canonical Wnt signaling, and increase the expression of LC3, an autophagy marker. When FZD7-NS and CQ are applied together, they reduce the expression of several stemness genes in TNBC cells, leading to inhibition of TNBC cell migration and self-renewal. Notably, co-delivery of FZD7-NS and CQ is more effective than either therapy alone or the combination of CQ with free FZD7 antibodies. This demonstrates that the nanocarrier design is important to its therapeutic utility. Overall, these findings indicate that combined regulation of Wnt signaling and autophagy by FZD7-NS and CQ is a promising strategy to combat TNBC.
Anastomotic stenosis (AS) after colorectal surgery was treated with balloon dilation, endoscopic procedure or surgery. The endoscopic procedures including dilation, electrocautery incision, or radial incision and cutting (RIC) were preferred because of lower complication rates than surgery and are less invasive. Endoscopic RIC has a greater success rate than dilation methods. Most reports showed that repeated RICs were needed to maintain patency of the anastomosis. We report that single session RIC was applied only to treatment-naive patients with AS.
Two female patients presented with AS. One patient had advanced rectal cancer and the other had a refractory stenosis following surgery for endometriosis at sigmoid colon. The endoscopic RIC procedure was performed as follows. A single small incision was carefully made to increase the view of the proximal colon and the incision was expanded until the surgical stapling line. Finally, we made a further circumferential excision with endoscopic knife along the inner border of the surgical staple line. At the end of the procedure, the standard colonoscope was able to pass freely through the widened opening. All patients showed improved AS after a single session of RIC without immediate or delayed procedure-related complications. Follow-up colonoscopy at 7 and 8 mo after endoscopic RIC revealed intact anastomotic sites in both patients. No treatment-related adverse events or recurrence of the stenosis was demonstrated during follow-up periods of 20 and 23 mo.
The endoscopic RIC may play a role as one of treatment options for treatment-naive AS with short stenotic lengths.
The endoscopic RIC may play a role as one of treatment options for treatment-naive AS with short stenotic lengths.
Self-renewal of gastric cancer stem cells (GCSCs) is considered to be the underlying cause of the metastasis, drug resistance, and recurrence of gastric cancer (GC).
To characterize the expression of stem cell-related genes in GC.
RNA sequencing results and clinical data for gastric adenoma and adenocarcinoma samples were obtained from The Cancer Genome Atlas database, and the results of the GC mRNA expression-based stemness index (mRNAsi) were analyzed. Weighted gene coexpression network analysis was then used to find modules of interest and their key genes. Survival analysis of key genes was performed using the online tool Kaplan-Meier Plotter, and the online database Oncomine was used to assess the expression of key genes in GC.
mRNAsi was significantly upregulated in GC tissues compared to normal gastric tissues (
< 0.0001). A total of 16 modules were obtained from the gene coexpression network; the brown module was most positively correlated with mRNAsi. Sixteen key genes (
,
,
,
,
,
,
,
,
,
,
,
,
,
,
, and
) were identified in the brown module. The functional and pathway enrichment analyses showed that the key genes were significantly enriched in the spindle cellular component, the sister chromatid segregation biological process, the motor activity molecular function, and the cell cycle and homologous recombination pathways. Survival analysis and Oncomine analysis revealed that the prognosis of patients with GC and the expression of three genes (
,
and
) were consistently related.
Sixteen key genes are primarily associated with stem cell self-renewal and cell proliferation characteristics.
,
, and
are the most likely therapeutic targets for inhibiting the stemness characteristics of GC cells.
Sixteen key genes are primarily associated with stem cell self-renewal and cell proliferation characteristics. RAD54L, TPX2, and XRCC2 are the most likely therapeutic targets for inhibiting the stemness characteristics of GC cells.An investigation was carried out to characterize the microstructure and bonding properties of the zirconium-carbon steel explosive clad. The microstructure and the composition of the clad were characterized using optical microscopy and scanning electron microscopy. Bonding properties were inspected by using bending and shearing tests. The examination results indicate that the R60702 and Cr70 plates were joined successfully without visible defects. The interface wave is symmetrical. There is no element diffusion across the interface of the clad plate. There are melt blocks at the interface. Bending and shearing test results indicate that the bonding properties of the clad meet the requirements of the ASTM B898 specification. And after shell rolling, no delamination appeared at the interface. Thus, it indicates that the clad plates have good bonding quality and meet the processing requirement.
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