Purpose. The purpose of the current meta-analysis was to evaluate whether multidisciplinary team improved overall survival of colorectal cancer. Methods. PubMed, EMBASE, and Cochrane Library database ...were searched from inception to October 25, 2020. The hazard ratio (HR) and 95% confidence (CI) of overall survival (OS) were calculated. Results. A total of 11 studies with 30814 patients were included in this meta-analysis. After pooling the HRs, the MDT group was associated with better OS compared with the non-MDT group (HR=0.81, 95% CI 0.69-0.94, p=0.005). In subgroup analysis of stage IV colorectal cancer, the MDT group was associated with better OS as well (HR=0.73, 95% CI 0.59-0.90, p=0.004). However, in terms of postoperative mortality, no significant difference was found between MDT and non-MDT groups (OR=0.84, 95% CI 0.44-1.61, p=0.60). Conclusion. MDT could improve OS of colorectal cancer patients.
Primary liver cancer is a lethal cancer. The phosphatidylinositol 3-kinase (PI3K)–Akt–mammalian target of rapamycin (mTOR) pathway has been implicated in the pathogenesis of liver cancer. Gomisin N ...(GN), a lignan isolated from the dried fruits of Schisandra chinensis (Turca.) Baill., has been reported to reduce viability of, and induce apoptosis in, HepG2 liver cancer cells. In preadipocytes, GN was found to inhibit Akt activity. In the present study, Akt signaling-related anti-liver cancer mechanisms of GN were investigated. We confirmed that GN reduces cell viability of, and triggers apoptosis in, more liver cancer cell lines. Mechanistic studies revealed that GN lowers protein levels of phospho-PI3K (p85 tyrosine (Tyr)458), phospho-Akt (serine (Ser)473), and Akt downstream molecules Mcl-1 in HepG2 and HCCLM3 cells. Meanwhile, GN activates mTOR and inhibits ULK1 (a negative downstream effector of mTOR) activities. Activation of mTOR has been reported to suppress ULK1 activity and repress autophagy. Indeed, we observed that GN inhibits autophagy in liver cancer cells. In summary, we for the first time demonstrated that GN inhibits the PI3K–Akt pathway and regulates the mTOR–ULK1 pathway in liver cancer cells.
Artificial synapses are the key building blocks for low‐power neuromorphic computing that can go beyond the constraints of von Neumann architecture. In comparison with two‐terminal memristors and ...three‐terminal transistors with filament‐formation and charge‐trapping mechanisms, emerging electrolyte‐gated transistors (EGTs) have been demonstrated as a promising candidate for neuromorphic applications due to their prominent analog switching performance. Here, a novel graphdiyne (GDY)/MoS2‐based EGT is proposed, where an ion‐storage layer (GDY) is adopted to EGTs for the first time. Benefitting from this Li‐ion‐storage layer, the GDY/MoS2‐based EGT features a robust stability (variation < 1% for over 2000 cycles), an ultralow energy consumption (50 aJ µm−2), and long retention characteristics (>104 s). In addition, a quasi‐linear conductance update with low noise (1.3%), an ultrahigh Gmax/Gmin ratio (103), and an ultralow readout conductance (<10 nS) have been demonstrated by this device, enabling the implementation of the neuromorphic computing with near‐ideal accuracies. Moreover, the non‐volatile characteristics of the GDY/MoS2‐based EGT enable it to demonstrate logic‐in‐memory functions, which can execute logic processing and store logic results in a single device. These results highlight the potential of the GDY/MoS2‐based EGT for next‐generation low‐power electronics beyond von Neumann architecture.
A novel graphdiyne (GDY)/MoS2‐based electrolyte‐gated transistor using GDY as a Li‐ion‐storage layer is proposed, which features robust stability and flexibility, an ultralow energy consumption, a long retention time, a quasi‐linear weight update with low noise, an ultrahigh Gmax/Gmin ratio, and an ultralow readout conductance. This GDY/MoS2‐based EGT has demonstrated its potential in applications of neuromorphic computing and in‐memory computing.
The brown planthopper, Nilaparvata lugens, the most destructive pest of rice, is a typical monophagous herbivore that feeds exclusively on rice sap, which migrates over long distances. Outbreaks of ...it have re-occurred approximately every three years in Asia. It has also been used as a model system for ecological studies and for developing effective pest management. To better understand how a monophagous sap-sucking arthropod herbivore has adapted to its exclusive host selection and to provide insights to improve pest control, we analyzed the genomes of the brown planthopper and its two endosymbionts.
We describe the 1.14 gigabase planthopper draft genome and the genomes of two microbial endosymbionts that permit the planthopper to forage exclusively on rice fields. Only 40.8% of the 27,571 identified Nilaparvata protein coding genes have detectable shared homology with the proteomes of the other 14 arthropods included in this study, reflecting large-scale gene losses including in evolutionarily conserved gene families and biochemical pathways. These unique genomic features are functionally associated with the animal's exclusive plant host selection. Genes missing from the insect in conserved biochemical pathways that are essential for its survival on the nutritionally imbalanced sap diet are present in the genomes of its microbial endosymbionts, which have evolved to complement the mutualistic nutritional needs of the host.
Our study reveals a series of complex adaptations of the brown planthopper involving a variety of biological processes, that result in its highly destructive impact on the exclusive host rice. All these findings highlight potential directions for effective pest control of the planthopper.
Malignant melanoma is aggressive and has a high mortality rate. Toll-like receptor 4 (TLR4) has been linked to melanoma growth, angiogenesis and metastasis. However, signal transduction mediated by ...TLR4 for driving melanoma progression is not fully understood. Signal transducer and activator of transcription 3 (STAT3) has been identified as a major oncogene in melanoma progression. We found: that TLR4 expression positively correlates with activation/phosphorylation of STAT3 in human melanoma samples; that TLR4 ligands activate STAT3 through MYD88 and TRIF in melanoma cells; and that intratumoral activation of TLR4 increases STAT3 activation in the tumor and promotes tumor growth, angiogenesis, epithelial-mesenchymal transition (EMT) and the formation of an immunosuppressive tumor microenvironment in mice. Further, we found that the effects mediated by activating TLR4 are weakened by suppressing STAT3 function with a dominant negative STAT3 variant in melanoma. Collectively, our work identifies STAT3 activation as a key event in TLR4 signaling-mediated melanoma progression, shedding new light on the pathophysiology of melanoma.
The purpose of this study is to analyze the effect of body mass index (BMI) on patients with concurrent colorectal cancer (CRC) and type 2 diabetes mellitus (T2DM).
Patients who underwent primary ...radical CRC surgery from Jan 2011 to Jan 2020 were retrospectively collected. The perioperative information, overall survival (OS) and disease-free survival (DFS) were compared between the higher BMI group and the lower BMI group.
A total of 574 patients with concurrent CRC and T2DM were included in this study. The higher BMI group had higher portion of hypertension (p < 0.01) and coronary heart disease (CHD) (p < 0.01). Furthermore, the higher BMI group had better OS (p = 0.016) and DFS (p = 0.040) than the lower BMI group in stage II CRC. In multivariate analysis, age (OS: p = 0.002, HR = 2.016, 95% CI = 1.307-3.109/ DFS: p = 0.003, HR = 1.847, 95% CI = 1.230-2.772), TNM stage (OS: p < 0.01, HR = 1.667, 95% CI = 1.281-2.169/ DFS: p = 0.001, HR = 1.545, 95% CI = 1.207-1.977), overall complications (OS: p = 0.004, HR = 1.837, 95% CI = 1.218-2.880/ DFS: p = 0.006, HR = 1.783, 95% CI = 1.184-2.686) and major complications (OS: p = 0.005, HR = 2.819, 95% CI = 1.376-5.774/ DFS: p = 0.014, HR = 2.414, 95% CI = 1.196-4.870) were independent factors of OS and DFS. Moreover, BMI (p = 0.019, HR = 0.413, 95% CI = 0.197-0.864) was an independent factor of OS in stage II CRC.
Higher BMI was associated with better OS in diabetic patients with stage II CRC.
The goal of replenishing the cardiomyocyte (CM) population using regenerative therapies following myocardial infarction (MI) is hampered by the limited regeneration capacity of adult CMs, partially ...due to their withdrawal from the cell cycle. Here, we show that microRNA-128 (miR-128) is upregulated in CMs during the postnatal switch from proliferation to terminal differentiation. In neonatal mice, cardiac-specific overexpression of miR-128 impairs CM proliferation and cardiac function, while miR-128 deletion extends proliferation of postnatal CMs by enhancing expression of the chromatin modifier SUZ12, which suppresses p27 (cyclin-dependent kinase inhibitor) expression and activates the positive cell cycle regulators Cyclin E and CDK2. Furthermore, deletion of miR-128 promotes cell cycle re-entry of adult CMs, thereby reducing the levels of fibrosis, and attenuating cardiac dysfunction in response to MI. These results suggest that miR-128 serves as a critical regulator of endogenous CM proliferation, and might be a novel therapeutic target for heart repair.
Abstract
Porcine epidemic diarrhea (PED) is a highly contagious swine disease caused by porcine epidemic diarrhea virus (PEDV). PED causes enteric disorders with an exceptionally high fatality in ...neonates, bringing substantial economic losses in the pork industry. The trimeric spike (S) glycoprotein of PEDV is responsible for virus-host recognition, membrane fusion, and is the main target for vaccine development and antigenic analysis. The atomic structures of the recombinant PEDV S proteins of two different strains have been reported, but they reveal distinct N-terminal domain 0 (D0) architectures that may correspond to different functional states. The existence of the D0 is a unique feature of alphacoronavirus. Here we combined cryo-electron tomography (cryo-ET) and cryo-electron microscopy (cryo-EM) to demonstrate in situ the asynchronous S protein D0 motions on intact viral particles of a highly virulent PEDV Pintung 52 strain. We further determined the cryo-EM structure of the recombinant S protein derived from a porcine cell line, which revealed additional domain motions likely associated with receptor binding. By integrating mass spectrometry and cryo-EM, we delineated the complex compositions and spatial distribution of the PEDV S protein N-glycans, and demonstrated the functional role of a key N-glycan in modulating the D0 conformation.
The purpose of the current study is to analyze the difference of short-term and oncologic outcomes between younger and older colorectal cancer (CRC) patients who underwent primary CRC surgery using a ...propensity score matching (PSM) analysis.
We retrospectively collected CRC patients who underwent primary surgery in a single clinical database from Jan 2011 to Jan 2020. The short-term and oncologic outcomes were compared between younger aged group and older aged group.
A total of 4599 patients were included in this study, and there were 4196 patients in older aged group and 403 patients in younger aged group. After 1:1 ratio PSM, there were 401 patients in each group. No significant difference was found in terms of baseline information after PSM (p>0.05). Younger aged group had larger retrieved lymph nodes before (p<0.001) and after PSM (p=0.001) than older aged group. In multivariate analysis, younger age was an independent predictor of better overall survival (OS) (p<0.001, HR=2.303, 95% CI=1.658-3.199) and disease-free survival (DFS) (p=0.008, HR=1.425, 95% CI=1.098-1.850). In terms of different tumor stage after PSM, younger aged group had better OS than older group in stage II (p<0.001) and stage IV (p=0.028) CRC, and younger aged group had better DFS than older group in stage II (p=0.016) CRC.
Younger CRC patients had larger retrieved lymph nodes and better prognosis than older CRC patients after primary CRC surgery.
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