Abdiaagesen5072
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. 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. selleck kinase inhibitor 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.Nanoscale wear affects the performance of atomic force microscopy (AFM)-based measurements for all applications including process control measurements and nanoelectronics characterization. As such, methods to prevent or reduce AFM tip wear is an area of active research. However, most prior work has been on conventional AFMs rather than critical dimension AFM (CD-AFM). Hence, less is known about CD-AFM tip-wear. Given that tip-wear directly affects the accuracy of dimensional measurements, a basic understanding of CD-AFM tip wear is needed. Toward this goal, we evaluated the wear performance of electron beam deposited CD-AFM tips. Using a continuous scanning strategy, we evaluated the overall wear rate and tip lifetime and compared these with those of silicon-based CD-AFM tips. Our data show improved tip lifetime of as much as a factor of five and reduced wear rates of more than 17 times. Such improvements in wear rate means less measurement variability and lower cost.Diffuse astrocytoma is an infiltrating type of glioma (World Health Organization grade II), which even with histopathology, is difficult to diagnose. Magnetic resonance imaging (MRI) is the cornerstone for diagnoses and follow-up of brain gliomas. This report describes a case of diffuse astrocytoma in a 48-year-old man who presented with sudden right-sided weakness and repeated convulsive attacks. On brain computed tomography, the case was diagnosed and treated as an acute infarction. Ten days later, the patient returned with a total loss of consciousness. Brain MRI images revealed an irregularly outlined lesion involving the splenium of the corpus callosum that extended into the left periventricular parietal lobe of the brain with cystic foci in the septum pellucidum. Contrast-enhanced and new sequences of MRI was helpful in approach to diagnosis because of its superior tissue characterization. The histopathology results ultimately confirmed the diagnosis of diffuse astrocytoma. The patient died postoperatively.Metastatic tumors of the nasal cavity and paranasal sinuses are much less common than primary cancer in this location. The clinical symptomatology is not specific. We report a case of frontal metastasis of a 49-year-old patient treated for a rectal adenocarcinoma without other secondary localizations. The treatment is based on radiotherapy or chemotherapy. Hence the value of recognizing sinus metastases and differentiating them from infection affection.Tracheal diverticulum is observed in 1%-4% of the population, however, multiple tracheal diverticula are a rare occurrence. In this paper, we present a 75-year-old male, who was referred to a computed tomography-scan of the neck, chest, abdomen, and pelvis because of an unintended weight loss, fatigue, and a smoking history of 60 pack-years. A definitive cause for the symptoms was not found, however as an incidental finding, the patient was diagnosed with multiple tracheal diverticula along the back wall of trachea and left main bronchus. Despite the rare occurrence, it is important to recognize multiple tracheal diverticula in the diagnostic process, because of the possibility of either removing the diverticula or initiating prophylactic actions to prevent complications such as empyema and pneumomediastinum.Arachnoid cysts are benign masses that represent a relatively small percentage of intracranial lesions. Spontaneous rupture of an arachnoid cyst resulting in a subdural hygroma is a very rare event. We report a case of a pediatric patient with a history of an arachnoid cyst and chronic headaches presenting with bilateral papilledema, worsening headaches, and no history of head trauma. Magnetic resonance imaging of the brain revealed an extra-axial cystic lesion in the right middle cranial fossa, similar to an arachnoid cyst seen on previous imaging. A new right subdural collection similar to the cerebral spinal fluid signal causing mass effect on brain parenchyma was determined to represent a subdural hygroma. Craniotomy was performed to evacuate the subdural hygroma as well as cyst fenestration. We report this case to emphasize the importance of considering spontaneous rupture of an arachnoid cyst as a differential diagnosis despite absence of head trauma.There have been few reports of pulmonary arteriovenous malformations complicated by hemoptysis. Herein, we present our experience and provided a review of the literature. A man in his 80s came to our hospital with a chief complaint of hemoptysis, and a simple computed tomography showed a consolidation in the right lower lobe of the lung. He was treated for bacterial pneumonia, and his symptoms and a consolidation resolved, but similar episodes continued afterwards. About 18 months after the initial disease onset, the patient had hemoptysis and came to our hospital again. He was diagnosed with pulmonary arteriovenous malformation due to the presence of a lumpy, mass-like dilatation in the peripheral arteries. With the suspicion that the hemoptysis was caused by pulmonary arteriovenous malformations, the patient underwent coil embolization, and his symptoms gradually resolved. Computed tomography also showed improvement in shadowing. The hidden arteriovenous malformation was buried by a dense pulmonary field shadow; thus, it was diagnosed after a long time.
