Conventional therapies for late‐stage colorectal cancer (CRC) have limited effects because of chemoresistance, recurrence, and metastasis. The “hidden” proteins/peptides encoded by long noncoding ...RNAs (lncRNAs) may be a novel resource bank for therapeutic options for patients with cancer. Here, lncRNA LOC90024 is discovered to encode a small 130‐amino acid protein that interacts with several splicing regulators, such as serine‐ and arginine‐rich splicing factor 3 (SRSF3), to regulate mRNA splicing, and the protein thus is named “Splicing Regulatory Small Protein” (SRSP). SRSP, but not LOC90024 lncRNA itself, promotes CRC tumorigenesis and progression, while silencing of SRSP suppresses CRC tumorigenesis. Mechanistically, SRSP increases the binding of SRSF3 to exon 3 of transcription factor Sp4, resulting in the inclusion of Sp4 exon 3 to induce the formation of the “cancerous” long Sp4 isoform (L‐Sp4 protein) and inhibit the formation of the “noncancerous” short Sp4 isoform (S‐Sp4 peptide), which lacks the transactivation domain. The upregulated SRSP level is positively associated with malignant phenotypes and poor prognosis in patients with CRC. Collectively, the findings uncover that a lncRNA‐encoded small protein SRSP induces “cancerous” Sp4 splicing variant formation and may be a potential prognostic biomarker and therapeutic target for patients with CRC.
The “hidden” proteins/peptides encoded by long noncoding RNAs (lncRNAs) may be a novel resource bank for therapeutic options for patients with cancer. The lncRNA LOC90024 encodes a small 130‐amino acid protein “Splicing Regulatory Small Protein” that binds to splicing regulator, serine‐ and arginine‐rich splicing factor 3 to promote the “cancerous” RNA splicing of the transcription factor Sp4, thereby promoting tumorigenesis.
Abstract The epithelial-mesenchymal transition (EMT) plays a crucial role in pancreatic ductal adenocarcinoma (PDAC) development and progression. TWIST activated by intra-tumoral hypoxia functions to ...promote the EMT. We hypothesized that TWIST and the downstream gene pathway could mediate PDAC progression under hypoxia. Therefore, 90 PDAC tissue specimens were immunostained for TWIST and other proteins. Pancreatic cancer cell lines were used for in vitro experiments and nude mice were used to confirm the in vivo data. Expression of TWIST and HIF-1α proteins was significantly upregulated, whereas expression of E-cadherin and p16 was down-regulated in PDAC tissues compared to that of non-tumor tissues and in tumor tissues obtained from patients with tumor involving splenic artery than those without splenic artery involvement. Up-regulated TWIST in tumor tissues were associated with worse prognosis in PDAC patients. The in vitro data showed that HIF-1α-induced TWIST overexpression promoted tumor cell growth and EMT under a hypoxic condition via TWIST interaction with Ring1B and EZH2. In vivo data showed that TWIST overexpression or a hypoxic condition induce xenograft growth, abdominal metastasis and low mouse survival, whereas knockdown of either Ring1B or EZH2 expression suppressed tumor xenograft growth and metastasis and prolonged survival of nude mice. TWIST was the key player in promotion of pancreatic cancer development and metastasis under a hypoxic condition through interaction with Ring1B and EZH2 to regulate expression of E-cadherin and p16 proteins in pancreatic cancer cells.
Memristors with small size, fast speed, low power, CMOS compatibility and nonvolatile modulation of device resistance are promising candidates for the next-generation data storage and in-memory logic ...computing paradigm. In comparison to the binary logics enabled by memristor devices, multi-valued logics can provide higher computation efficiency with simple operation scheme, reduced circuit complexity, and smaller chip area. In this contribution, we demonstrate that all the 27 univariate ternary logic operations can be realized with a single ZnO three-state resistive switching memristor in at most three steps. The nonvolatile modulation characteristics of the memristor allow the read step to be independent of the logic operation and capacitate logic-in-memory applications. The present methodology could be beneficial for constructing future high-performance computation architectures.
To understand the morphological and structural characteristics of root nodules in Podocarpus macrophyllus and their development, this study prepared P. macrophyllus root nodule samples at the young, ...mature and senescent stages. Optical microscopy and transmission electron microscopy (TEM) revealed that new nodules can be formed on roots and senescent nodules; new nodules formed on the roots are nearly spherical and have an internal structure similar to finite nodules; new nodules on senescent nodules are formed by extension and differentiation of the vascular cylinder of the original nodules; and these new nodules are nested at the base of the original nodules, which create growth space for new nodules by dissociating the cortical tissue; clusters of nodules are formed after extensive accumulation, and the growth pattern is similar to that of infinite nodules; the symbiotic bacteria of P. macrophyllus root nodules mainly invade from the epidermal intercellular space of the roots and migrate along the intercellular space of the nodule cortex; infected nodule cortex cells have a well‐developed inner membrane system and enlarged and loose nuclei; and unique Frankia vesicles, and rhizobia cysts, and bacteriophages can all develop. Compared with common leguminous and nonleguminous plant nodules, P. macrophyllus root nodules are more complex in morphology, structure and composition. From the perspective of plant system evolution, the nodules in P. macrophyllus most likely represent two evolutionary patterns inlcuding the Rhizobium nodules in leguminous angiosperms and Frankia nodules in nonleguminous angiosperms. The conclusion of this study provides a theoretical basis for the developmental biology of P. macrophyllus root nodules and the evolutionary pattern of plant symbionts.
Abstract
N
6
-methyladenosine (m
6
A) is the most prevalent modification in eukaryotic RNAs. The biological importance of m
6
A relies on m
6
A readers, which control mRNA fate and function. However, ...it remains unexplored whether additional regulatory subunits of m
6
A readers are involved in the m
6
A recognition on RNAs. Here we discover that the long noncoding RNA (lncRNA)
LINC00266-1
encodes a 71-amino acid peptide. The peptide mainly interacts with the RNA-binding proteins, including the m
6
A reader IGF2BP1, and is thus named “RNA-binding regulatory peptide” (RBRP). RBRP binds to IGF2BP1 and strengthens m
6
A recognition by IGF2BP1 on RNAs, such as
c-Myc
mRNA, to increase the mRNA stability and expression of
c-Myc
, thereby promoting tumorigenesis. Cancer patients with RBRP
high
have a poor prognosis. Thus, the oncopeptide RBRP encoded by
LINC00266-1
is a regulatory subunit of m
6
A readers and strengthens m
6
A recognition on the target RNAs by the m
6
A reader to exert its oncogenic functions.
Memristors, which feature small sizes, fast speeds, low power, CMOS compatibility and nonvolatile modulation of device resistance, are promising candidates for next-generation data storage and ...in-memory computing paradigms. Compared to the binary logics enabled by memristor devices, ternary logics with larger information-carrying capacity can provide higher computation efficiency with simple operation schemes, reduced circuit complexity and smaller chip areas. In this study, we report the fabrication of memristor devices based on nano-columnar crystalline ZnO thin films; they show symmetric and reliable multi-level resistive switching characteristics over three hundred cycles, which benefits the implementation of univariate ternary logic operations. Experimental results demonstrate that a three-valued logic complete set can be realized by the univariate operations of the present ZnO memristor device, and a ternary multiplier unit circuit is designed for potential applications. The present methodology can be beneficial for constructing future high-performance computation architectures.
Memristors, which feature small sizes, fast speeds, low power, CMOS compatibility and nonvolatile modulation of device resistance, are promising candidates for next-generation data storage and in-memory computing paradigms.
Remifentanil is widely used for ultrasound-guided percutaneous radiofrequency ablation (RFA) of small hepatocellular carcinoma (HCC). We determined whether dexmedetomidine could be an alternative to ...remifentanil for RFA of HCC under general anesthesia with sevoflurane.
We prospectively randomized patients scheduled to undergo RFA for HCC to a dexmedetomidine (DEX) group or remifentanil (REMI) group (47 patients each). In the DEX group, a bolus infusion (0.4 μg kg
) was started 15 min before anesthesia induction and continued at 0.2 μg kg
h
until 10 min before the end of surgery. In the REMI group, 3 μg kg
h
of remifentanil was administered from 15 min before anesthesia induction to the end of the surgery. The primary endpoint was postoperative pain intensity. Secondary endpoints included analgesic requirement, postoperative liver function, patient comfort, and hemodynamic changes. Group allocation was concealed from patients and data analysts but not from anesthesiologists.
Postoperative pain intensity, analgesic consumption, comfort, liver function, and time to emergence and extubation did not differ between the two groups. Heart rate, but not mean arterial pressure, was significantly lower in the DEX group than in the REMI group, at 1 min after intubation and from 30 min after the start of the surgery until anesthesia recovery. Sevoflurane concentration and dosage were significantly lower in the DEX group than in the REMI group.
During RFA for HCC, low-dose dexmedetomidine reduced the heart rate and need for inhalational anesthetics, without exacerbating postoperative discomfort or liver dysfunction. Although it did not exhibit outstanding advantages over remifentanil in terms of pain management, dexmedetomidine could be a safe alternative adjuvant for RFA under sevoflurane anesthesia.
Chinese Clinical Trial Registry, ChiCTR-OPC-15006613 . Registered on 16 June 2015.
Carbon materials are crucially important for the realization of potassium-ion batteries. However, the potassium storage mechanisms in various carbon materials are incompletely understood. Herein, ...solid-state
13
C nuclear magnetic resonance (NMR) spectroscopy coupled with Raman and X-ray diffraction (XRD) techniques are employed to study the reaction mechanism in a soft carbon quantitatively. It is revealed that the insertion of potassium ions into the soft carbon firstly induces a transformation of the disordered region to short-range ordered stacking, involving both the pristine local unorganized and organized carbon layers. Subsequently, potassium ions intercalate into the rearranged carbon structure, finally producing the nano-sized KC
8
. Moreover, a remarkable capacity of 322 mAh·g
−1
with a low mid potassiation voltage of < 0.3 V is present for the prepared soft carbon, which is on account of the underlying potassium storage sites, including the disordered stacking carbon as a main component of the soft carbon. These results suggest that regulating the disordered stacking region in the turbostratic structure of soft carbon is a critical issue for further improving the potassium storage performance.
Graphical Abstract
To the Editor: Charcot-Marie-Tooth disease (CMT) encompasses a genetically heterogeneous group of inherited neuropathies, characterized by progressive distal muscle weakness and atrophy, sensory ...deficits, impaired tendon reflexes, and foot deformities. ...CMT needs to be distinguished from several entities including systemic disorders with neuropathy and other types of hereditary neuropathy. Dr. Wei Luo, Department of Neurology, The Second Affiliated Hospital, Zhejiang University School of Medicine, No.88 Jiefang Road, Hangzhou, Zhejiang 310009, China E-Mail: luoweirock@zju.edu.cn How to cite this article:
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