Colorectal cancer is one of the most common malignancies worldwide. Recently, a novel circular RNA, ciRS-7, was proposed to be a potential miR-7 sponge. As miR-7, a putative tumor-suppressor, ...regulates the expression of several important drivers of colorectal cancer, we analyzed the clinical significance of ciRS-7 in colorectal cancer patients.
Initially, we evaluated the expression levels of ciRS-7 in a training cohort comprising of 153 primary colorectal cancer tissues and 44 matched normal mucosae. We subsequently confirmed its clinical relevance in an independent validation cohort (
= 165), and evaluated the effect of ciRS-7 on miR-7, and its target genes EGFR and RAF1. Functional analyses were performed in cell lines and an animal model to support clinical findings.
Our data revealed that ciRS-7 was significantly upregulated in colorectal cancer tissues compared with matched normal mucosae (
= 0.0018), and its overexpression was associated with poor patient survival (
= 0.0224 and 0.0061 in the training and validation cohorts, respectively). Multivariate survival analysis revealed that ciRS-7 emerged as an independent risk factor for overall survival (
= 0.0656 and 0.0324 in the training and validation cohorts, respectively). Overexpression of ciRS-7 in HCT116 and HT29 cells led to the blocking of miR-7 and resulted in a more aggressive oncogenic phenotype, and ciRS-7 overexpression permitted the inhibition of miR-7 and subsequent activation of EGFR and RAF1 oncogenes.
CiRS-7 is a promising prognostic biomarker in colorectal cancer patients and may serve as a therapeutic target for reducing EGFR-RAF1 activity in colorectal cancer patients.
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In the last few decades, N‐heterocyclic carbene (NHC) ligands, characterized by attractive features, have increased their presence in transition‐metal catalysis. However, chiral NHC ligands still ...require further design enhancement to realize far more exciting synthetic applications. This review documents advances in chiral NHC ligands, focusing on planar‐chiral ferrocene‐based NHCs. As the basic shape of most classes of NHC rings is planar, it seems rational to employ a planar‐chiral element in the design of chiral NHC ligands.
Planar‐chiral ferrocene ligands: Chiral N‐heterocyclic carbene (NHCs) ligands offer the possibility for use in a wide range of transition‐metal catalyzes. In this review, an overview is presented of the developing field, focusing on planar‐chiral ferrocene‐based NHC ligands.
Development of resistance to chemotherapeutic drugs is a major challenge in the care of patients with pancreatic ductal adenocarcinoma (PDAC). Acquired resistance to chemotherapeutic agents in PDAC ...has been linked to a subset of cancer cells termed 'cancer stem cells' (CSCs). Therefore, an improved understanding of the molecular events underlying the development of pancreatic CSCs is required to identify new therapeutic targets to overcome chemoresistance. Accumulating evidence indicates that curcumin, a phenolic compound extracted from turmeric, can overcome de novo chemoresistance and re-sensitize tumors to various chemotherapeutic agents. However, the underlying mechanisms for curcumin-mediated chemosensitization remain unclear. The Enhancer of Zeste Homolog-2 (EZH2) subunit of Polycomb Repressive Complex 2 (PRC2) was recently identified as a key player regulating drug resistance. EZH2 mediates interaction with several long non-coding RNAs (lncRNAs) to modulate epithelial-mesenchymal transition and cancer stemness, phenomena commonly associated with drug resistance. Here, we report the re-sensitization of chemoresistant PDAC cells by curcumin through the inhibition of the PRC2-PVT1-c-Myc axis. Using gemcitabine-resistant PDAC cell lines, we found that curcumin sensitized chemoresistant cancer cells by inhibiting the expression of the PRC2 subunit EZH2 and its related lncRNA PVT1. Curcumin was also found to prevent the formation of spheroids, a hallmark of CSCs, and to down-regulate several self-renewal driving genes. In addition, we confirmed our in vitro findings in a xenograft mouse model where curcumin inhibited gemcitabine-resistant tumor growth. Overall, this study indicates clinical relevance for combining curcumin with chemotherapy to overcome chemoresistance in PDAC.
Conversion therapy for gastric cancer (GC) has been the subject of much recent attention. It is defined as a surgical treatment aiming at an R0 resection after chemotherapy for tumors that were ...originally unresectable or marginally resectable for technical and/or oncological reasons. However, the indications for resection remain to be clarified. In the present review, we focus on the biology and heterogeneous characteristics of stage IV GC and propose new categories of classification. Stage IV GC patients can be divided based on the absence (categories 1 and 2) or presence (categories 3 and 4) of macroscopically detectable peritoneal dissemination, which has a different biological outcome compared to hematological metastasis. Category 1 is defined oncologically as stage IV but the metastasis is technically resectable. Category 2 includes a marginally resectable metastasis or patients for whom the operation would not necessarily be the best choice. Category 3 includes a potentially unresectable metastasis of peritoneal dissemination that is only macroscopically detectable. Category 4 includes noncurable metastasis with peritoneal and other organ metastasis. The indications for conversion therapy might include the patients from category 2, some patients from category 3 and a very small number of patients from category 4. The longer survival can be expected for patients corresponding to categories 1, 2 and, to a lesser extent, 3, while the treatment of other patients focuses on “care.” The provision of conversion therapy for stage IV GC patients might be one of the main roles of surgical oncologists in the near future.
NH
-SCR (selective catalytic reduction) is important process for removal of NOx. However, water vapor included in exhaust gases critically inhibits the reaction in a low temperature range. Here, we ...report bulk W-substituted vanadium oxide catalysts for NH
-SCR at a low temperature (100-150 °C) and in the presence of water (~20 vol%). The 3.5 mol% W-substituted vanadium oxide shows >99% (dry) and ~93% (wet, 5-20 vol% water) NO conversion at 150 °C (250 ppm NO, 250 ppm NH
, 4% O
, SV = 40000 mL h
g
). Lewis acid sites of W-substituted vanadium oxide are converted to Brønsted acid sites under a wet condition while the distribution of Brønsted and Lewis acid sites does not change without tungsten. NH
species adsorbed on Brønsted acid sites react with NO accompanied by the reduction of V
sites at 150 °C. The high redox ability and reactivity of Brønsted acid sites are observed for bulk W-substituted vanadium oxide at a low temperature in the presence of water, and thus the catalytic cycle is less affected by water vapor.
In order to synthesize optically active amino acids containing the adamantane core, an enantioselective desymmetrization of adamantanes via rhodium‐catalyzed C−H bond amination was examined. After ...investigating various conditions, it was found that the coupling reaction between disubstituted adamantane and aryloxysulfonamide was catalyzed by Rh2(S‐TCPTTL)4 to furnish the desired products having up to 85% ee (e.r.=92.4: 7.6) (>99% ee after recrystallization). The synthetic utility of the enantioenriched products as chiral building blocks was demonstrated by transforming one of them into a dipeptide derivative and a Schiff‐base ligand. The absolute configuration of one of the amino acid derivatives was determined unambiguously by X‐ray single‐crystal structure analysis.
Background
It is important to determine the effect of clinical factors on several domains (symptoms, living status, and quality of life QOL) after gastrectomy to establish individualized therapeutic ...strategies. This study was designed to determine the factors—particularly surgical method—that influence certain domains after gastrectomy for proximal gastric cancer by using the Postgastrectomy Syndrome Assessment Scale-45 (PGSAS-45) questionnaire.
Methods
We conducted a nationwide study of PGSAS-45 questionnaire responses retrieved from 1950 (82.5%) patients from 70 institutions who had undergone gastrectomy for gastric cancer. Of these, 1,538 responses for proximal gastric cancer (1020 total gastrectomies and 518 proximal gastrectomies PGs) were examined.
Results
PG significantly and favorably affected four main outcome measures (MOMs): elderly affected 10 MOMs, male sex affected 4 MOMs, longer postoperative period affected 8 MOMs, preservation of the vagus nerve affected 1 MOM, adjuvant chemotherapy affected 1 MOM, clinical stage affected 2 MOMs, and more extensive lymph node dissection affected 2 MOMs. However, the laparoscopic approach had an adverse effect on MOMs and combined resection of other organs had no favorable effect on any MOMs.
Conclusions
This PGSAS NEXT study showed that it is better to perform PG for proximal gastric cancer, even for patients with advanced cancer, to obtain favorable postoperative QOL if oncological safety is guaranteed. Because the MOMs of PGSAS-45 are positively and negatively influenced by various background factors, it also is necessary to provide personalized care for each patient to prevent deterioration and further improve symptoms, living status, and QOL postoperatively.
Hand, foot, and mouth disease (HFMD) is a common febrile illness caused by enteroviruses in the Picornaviridae family. The major symptoms of HFMD are fever and a vesicular rash on the hand, foot, or ...oral mucosa. Acute meningitis and encephalitis are observed in rare cases. HFMD epidemics occur annually in Japan, usually in the summer season. Relatively large-scale outbreaks have occurred every two years since 2011. In this study, the epidemic patterns of HFMD in Japan are predicted four weeks in advance using a deep learning method. The time-series data were analyzed by a long short-term memory (LSTM) approach called a Recurrent Neural Network. The LSTM model was trained on the numbers of weekly HFMD cases in each prefecture. These data are reported in the Infectious Diseases Weekly Report, which compiles the national surveillance data from web sites at the National Institute of Infectious Diseases, Japan, under the Infectious Diseases Control Law. Consequently, our trained LSTM model distinguishes between relatively large-scale and small-scale epidemics. The trained model predicted the HFMD epidemics in 2018 and 2019, indicating that the LSTM approach can estimate the future epidemic patterns of HFMD in Japan.
The 20th century's robotic systems have been made from stiff materials, and much of the developments have pursued ever more accurate and dynamic robots, which thrive in industrial automation, and ...will probably continue to do so for decades to come. However, the 21st century's robotic legacy may very well become that of soft robots. This emerging domain is characterized by continuous soft structures that simultaneously fulfill the role of robotic link and actuator, where prime focus is on design and fabrication of robotic hardware instead of software control. These robots are anticipated to take a prominent role in delicate tasks where classic robots fail, such as in minimally invasive surgery, active prosthetics, and automation tasks involving delicate irregular objects. Central to the development of these robots is the fabrication of soft actuators. This article reviews a particularly attractive type of soft actuators that are driven by pressurized fluids. These actuators have recently gained traction on the one hand due to the technology push from better simulation tools and new manufacturing technologies, and on the other hand by a market pull from applications. This paper provides an overview of the different advanced soft actuator configurations, their design, fabrication, and applications.
The 21st century's robotic legacy may very well become that of soft robots, which show remarkable features superior to those of conventional robots in tasks requiring delicate manipulation and a high degree of maneuverability. This review discusses a particular type of soft actuators—elastic inflatable actuators—which are driven by pressurized fluids and allow for straightforward integration in soft robotics.