PRMT5 activates KLF5 by methylation to facilitate lung cancer.

The highly expressed oncogenic factor Krüppel-like factor 5 (KLF5) promotes various cancerous processes, such as cell growth, survival, anti-apoptosis, migration and metastasis, particularly in lung cancer. Nevertheless, the modifications to KLF5 after translation are poorly understood. Protein arginine methyltransferase 5 (PRMT5) is considered as an oncogene known to be involved in different types of carcinomas, including lung cancer. Here, we show that the expression levels of PRMT5 and KLF5 are highly expressed lung cancer. Moreover, PRMT5 interacts with KLF5 and facilitates the dimethylation of KLF5 at Arginine 41 in a manner that depends on methyltransferase activity. Downregulation or pharmaceutical suppression of PRMT5 reduces the expression of KLF5 and its downstream targets both in vitro and in vivo. Mechanistically, the dimethylation of KLF5 by PRMT5 promotes the maintenance and proliferation of lung cancer cells at least partially by stabilising KLF5 via regulation of the Akt/GSK3ß signalling axis. In summary, PRMT5 methylates KLF5 to prevent its degradation, thereby promoting the maintenance and proliferation of lung cancer cells. These results suggest that targeting PRMT5/KLF5 axis may offer a potential therapeutic strategy for lung cancer.

Functional analysis of differentially expressed circular RNAs in sheep subcutaneous fat.

BACKGROUND: Circular RNAs (circRNAs), as important non-coding RNAs (ncRNAs), are involved in many biological activities. However, the exact chemical mechanism behind fat accumulation is unknown. In this paper, we obtained the expression profiles of circRNAs using high-throughput sequencing and investigated their differential expression in subcutaneous fat tissue of Duolang and Small Tail Han sheep. RESULTS: From the transcriptomic analysis, 141 differentially expressed circRNAs were identified, comprising 61 up-regulated circRNAs and 80 down-regulated circRNAs. These host genes were primarily enriched in the MAPK and AMPK signaling pathways which is closely associated with fat deposition regulation. We identified circRNA812, circRNA91, and circRNA388 as vital genes in fat deposition by miRNA-circRNA target gene prediction. The functional annotation results of target genes of key circRNAs showed that the signaling pathways mainly included PI3K-Akt and AMPK. We constructed the competing endogenous RNA (ceRNA) regulatory network to study the role of circRNAs in sheep lipid deposition, and circRNA812, circRNA91, and circRNA388 can adsorb more miRNAs. NC_040253.1_5757, as the source of miRNA response element (MRE) among the three, may play an important role during the process of sheep fat deposition. CONCLUSIONS: Our study gives a systematic examination of the circRNA profiles expressed in sheep subcutaneous fat. These results from this study provide some new basis for understanding circRNA function and sheep fat metabolism.

Predictive value of systemic inflammatory markers for recurrence of papillary thyroid cancer.

BACKGROUND: Papillary thyroid cancer (PTC) is the most common type of differentiated thyroid cancer. Early identification of patients at higher risk of recurrence may allow to improve relevant follow-up strategies and plan tailored treatment. Inflammation play an important role in the prognosis of cancer. We aimed to explore the predictive value of systemic inflammatory markers in PTC recurrence. METHODS: We retrospectively enrolled 200 consecutive patients who were diagnosed with PTC and underwent curative resection at Lianyungang Oriental Hospital between January 2006 and December 2018. Clinicopathological characteristics, preoperative hematologic results were analyzed. The optimal cutoff values were calculated using x-tile software. The multivariate logistic regression and univariable survival analysis were performed by SPSS. RESULTS: Multivariable analysis showed that lymph node metastases (odds ratio [OR] = 2.506, 95% confidence interval [CI]: 1.226-5.119, p = 0.012) and higher monocyte-to-lymphocyte ratio (MLR) (OR = 2.100, 95% CI: 1.042-4.233, p = 0.038) were independent prognostic factors for tumor recurrence. The cutoff value 0.22 of MLR significantly predicted recurrence at 53.3% sensitivity and 67.9% specificity. Patients with MLR ≥ 0.22 exhibited significantly poor long-term prognosis (46.8%) compared to the counterpart (76.8%, p = 0.0004). CONCLUSIONS: Preoperative MLR significantly predicted PTC recurrence after curative resection, which may provide clues for early identification of patients at higher risk of PTC recurrence.

TRIM52 aggravated inflammation and pyroptosis in dextran sulfate sodium-induced inflammatory bowel disease through activation of the TLR4/NF-κBs pathway.

INTRODUCTION: Inflammatory bowel disease (IBD), which mainly leads to diarrhea, fatigue, stool blood, abdominal pain, and cramping, is threatening public health. Tripartite motif-containing 52 (TRIM52) has been reported to play an important role in inflammatory responses via activating the toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway. However, the causes of IBD need to be elucidated, and the function of TRIM52 in IBD remains unclear. Here, we demonstrated that TRIM52 aggravated inflammation and pyroptosis in dextran sulfate sodium (DSS)-induced IBD by activating TLR4/NF-κBs pathway. METHODS: The colitis model was established on mice through DSS induction. For the TRIM52 knockdown, the mice were infected with a recombinant adenoviral vector expressing sgRNAs targeting TRIM52. RT-qPCR, western blot, and immunohistochemistry were performed to verify TRIM52 expression in DSS-induced IBD. The body weight, disease activity index, colon length, and H&E staining were used to assess the IBD symptoms in mice with TRIM52 knockdown. The inflammatory responses were examined by RT-qPCR and ELISA measuring tumor necrosis factor-α (TNF-α), inter-leukin 6 (IL-6), and interleukin 1ß (IL-1ß). Furthermore, the pyroptosis in colon tissue was detected by western blot. Finally, the TLR4/NF-κBs pathway activity was also examined by western blot. RESULTS: TRIM52 expression was up-regulated in DSS-induced IBD, and knockdown of TRIM52 could alleviate the symptoms of IBD. TRIM52 knockdown retarded DSS-induced inflammatory response and inhibited DSS-induced pyroptosis in colon tissue. In addition, TRIM52 played a role in activating TLR4/NF-κBs pathway. CONCLUSION: Knockdown of TRIM52 alleviated inflammation and pyroptosis in IBD by regulating TLR4/NF-κBs pathway. TRIM52 is expected to be a novel diagnostic indicator for IBD and a target of therapeutic treatment.

Coptisine suppresses proliferation and inhibits metastasis in human pancreatic cancer PANC-1 cells.

The effects of coptisine against advanced stage of human pancreatic carcinoma PANC-1 cells was investigated in vitro. Coptisine (25-150 µM) treatment for 48 h caused dose-dependent cell growth inhibition by using CCK-8 assay. Additionally, coptisine was found to inhibit PANC-1 cells metastasis by the wound healing assay. Flow cytometry data indicated that coptisine (25-100 µM) exhibited dose-dependent G1 phase arrest and moderate reduction of S phase. Coptisine was also found to inhibit ERK phosphorylation and total ERK levels. Our research suggested that coptisine would be a potential therapeutic drug for the treatment of pancreatic cancer.

Nanochannel-Based Transport in an Interfacial Memristor Can Emulate the Analog Weight Modulation of Synapses.

By exploiting novel transport phenomena such as ion selectivity at the nanoscale, it has been shown that nanochannel systems can exhibit electrically controllable conductance, suggesting their potential use in neuromorphic devices. However, several critical features of biological synapses, particularly their conductance modulation, which is both memorable and gradual, have rarely been reported in these types of systems due to the fast flow property of typical inorganic electrolytes. In this work, we demonstrate that electrically manipulating the nanochannel conductance can result in nonvolatile conductance tuning capable of mimicking the analog behavior of synapses by introducing a room-temperature ionic liquid (IL) and a KCl solution into the two ends of a nanochannel system. The gradual conductance-tuning mechanism is identified through fluorescence measurements as the voltage-induced movement of the interface between the immiscible IL and KCl solution, while the successful memorization of the conductance tuning is ascribed to the large viscosity of the IL. We applied a nanochannel-based synapse to a handwritten digit-recognition task, reaching an accuracy of 94%. These promising results provide important guidance for the future design of nanochannel-based neuromorphic devices and the manipulation of nanochannel transport for computing.

Biomimetic Chiral Photonic Crystals.

Although it is well known that the amazing iridescent colors of the cuticle of beetles reflect the intricate nanoscale organization of bio-fibers, artificial inorganic materials with comparable optical responses have not yet been synthesized from abiotic nanoscale building blocks. Such materials could find broad applications, including in circular polarizers, to generate circularly polarized luminescence, or in lasers. Herein, we describe a general method for the fabrication of biomimetic chiral photonic crystals by Langmuir-Schaefer assembly of colloidal inorganic nanowires. We not only reproduced the intricate helical structure and circularly polarized color reflection observed in beetles, but also achieved the highest chiroptical activity with a dissymmetry factor of -1.6 ever reported for chiral inorganic nanostructures. More importantly, the programmable structural control based on the precise interlayer arrangement endows us with unprecedented freedom to manipulate the optical activity of as-fabricated chiral photonic crystals.

Reconfigurable logic in nanosecond Cu/GeTe/TiN filamentary memristors for energy-efficient in-memory computing.

Owing to the capability of integrating the information storage and computing in the same physical location, in-memory computing with memristors has become a research hotspot as a promising route for non von Neumann architecture. However, it is still a challenge to develop high performance devices as well as optimized logic methodologies to realize energy-efficient computing. Herein, filamentary Cu/GeTe/TiN memristor is reported to show satisfactory properties with nanosecond switching speed (<60 ns), low voltage operation (<2 V), high endurance (>104 cycles) and good retention (>104 s @85 °C). It is revealed that the charge carrier conduction mechanisms in high resistance and low resistance states are Schottky emission and hopping transport between the adjacent Cu clusters, respectively, based on the analysis of current-voltage behaviors and resistance-temperature characteristics. An intuitive picture is given to describe the dynamic processes of resistive switching. Moreover, based on the basic material implication (IMP) logic circuit, we proposed a reconfigurable logic method and experimentally implemented IMP, NOT, OR, and COPY logic functions. Design of a one-bit full adder with reduction in computational sequences and its validation in simulation further demonstrate the potential practical application. The results provide important progress towards understanding of resistive switching mechanism and realization of energy-efficient in-memory computing architecture.

Poly IC pretreatment suppresses B cell-mediated lupus-like autoimmunity through induction of Peli1.

Noncanonical NF-κB pathway is essential for the B cell activation and antibody production, which centralize the critical role of B cells in regulating the pathogenesis of systemic lupus erythematosus (SLE). We have previously demonstrated that Pellino1 (Peli1) negatively regulates noncanonical NF-κB activation and lupus autoimmunity. Here, we showed that poly IC is a potent inducer of Peli1 protein in mouse splenic B cells in dose- and time-dependent manners, and poly IC-induced Peli1 protein dramatically suppressed the activation of noncanonical NF-κB pathway. In addition, poly IC-pretreated B cells failed to induce lupus-like disease in BM12 CD4+ T cell-immunized mice. Accordingly, the induction of antibody-producing plasma cells and germinal center B cells, as well as the production of autoantibodies were significantly impaired in immunized µMT mice that were transferred with poly IC-pretreated B cells. Our findings demonstrate that poly IC-induced Peli1 negatively regulates the noncanonical NF-κB pathway in the context of restraining the pathogenesis of lupus-like disease.

Selective Inhibition of Lysine-Specific Demethylase 5A (KDM5A) Using a Rhodium(III) Complex for Triple-Negative Breast Cancer Therapy.

Lysine-specific demethylase 5A (KDM5A) has recently become a promising target for epigenetic therapy. In this study, we designed and synthesized metal complexes bearing ligands with reported demethylase and p27 modulating activities. The Rh(III) complex 1 was identified as a direct, selective and potent inhibitor of KDM5A that directly abrogate KDM5A demethylase activity via antagonizing the KDM5A-tri-/di-methylated histone 3 protein-protein interaction (PPI) in vitro and in cellulo. Complex 1 induced accumulation of H3K4me3 and H3K4me2 levels in cells, causing growth arrest at G1 phase in the triple-negative breast cancer (TNBC) cell lines, MDA-MB-231 and 4T1. Finally, 1 exhibited potent anti-tumor activity against TNBC xenografts in an in vivo mouse model, presumably via targeting of KDM5A and hence upregulating p27. Moreover, complex 1 was less toxic compared with two clinical drugs, cisplatin and doxorubicin. To our knowledge, complex 1 is the first metal-based KDM5A inhibitor reported in the literature. We anticipate that complex 1 may be used as a novel scaffold for the further development of more potent epigenetic agents against cancers, including TNBC.

Identification of differentially expressed genes between subcutaneous and intramuscular adipose tissue of Large White pig using RNA-seq.

To explore the molecular mechanisms of lipid accumulation in different types of adipose tissue, the transcriptomes of the subcutaneous and intramuscular adipose tissues from the Large White pig were determined using RNA-seq technology and bioinformatics methods. The differential gene expression profiles were identified and analyzed with the Gene Ontology, KEGG pathway and protein-protein interaction network strategies. There were 180 differentially expressed genes between the two adipose tissues. The genes up-regulated in the subcutaneous, as compared to intramuscular, adipose tissues were mainly involved in the biological processes related to lipid metabolism. The down-regulated genes were significantly enriched in MAPK signaling pathway, suggesting that this signaling pathway could have an important regulatory role(s) in adipocyte differentiation. In summary, differentially expressed genes between the subcutaneous and intramuscular adipose tissues were predominantly involved in lipid metabolism/accumulation and regulation of adipogenesis in the Large White pig.

Surface Defects Enhanced Visible Light Photocatalytic H2 Production for Zn-Cd-S Solid Solution.

In order to investigate the defect effect on photocatalytic performance of the visible light photocatalyst, Zn-Cd-S solid solution with surface defects is prepared in the hydrazine hydrate. X-ray photoelectron spectra and photoluminescence results confirm the existence of defects, such as sulfur vacancies, interstitial metal, and Zn and Cd in the low valence state on the top surface of solid solutions. The surface defects can be effectively removed by treating with sulfur vapor. The solid solution with surface defect exhibits a narrower band gap, wider light absorption range, and better photocatalytic perfomance. The optimized solid solution with defects exhibits 571 µmol h(-1) for 50 mg photocatalyst without loading Pt as cocatalyst under visible light irradiation, which is fourfold better than that of sulfur vapor treated samples. The wavelength dependence of photocatalytic activity discloses that the enhancement happens at each wavelength within the whole absorption range. The theoretical calculation shows that the surface defects induce the conduction band minimum and valence band maximum shift downward and upward, respectively. This constructs a type I junction between bulk and surface of solid solution, which promotes the migration of photogenerated charges toward the surface of nanostructure and leads to enhanced photocatalytic activity. Thus a new method to construct highly efficient visible light photocatalysts is opened.

Multiple rescattering processes in high-order harmonic generation from molecular system.

The molecular multiple rescattering processes have been theoretically investigated via solving the time-dependent Schrödinger equation. Not only has the physical model been established, but also the related rescatterings originating from recombination with parent nucleus and with neighboring nucleus have been distinguished. Moreover, it has shown that the rescatterings originating from recombination with parent nucleus are similar with those atomic rescatterings, while those rescatterings from recombination with neighboring nucleus both before and after reversing the direction of the laser field are more sensitive to the internuclear distance. With time-frequency distribution and classical electron dynamics, the underlying mechanisms are revealed.

Mimicking the brain functions of learning, forgetting and explicit/implicit memories with SrTiO3-based memristive devices.

To implement the complex brain functions of learning, forgetting and memory in a single electronic device is very advantageous for realizing artificial intelligence. As a proof of concept, memristive devices with a simple structure of Ni/Nb-SrTiO3/Ti were investigated in this work. The functions of learning, forgetting and memory were successfully mimicked using the memristive devices, and the "time-saving" effect of implicit memory was also demonstrated. The physics behind the brain functions is simply the modulation of the Schottky barrier at the Ni/SrTiO3 interface. The realization of various psychological functions in a single device simplifies the construction of the artificial neural network and facilitates the advent of artificial intelligence.

Impact of Water-Depletion Layer on Transport in Hydrophobic Nanochannels.

Recent experiments showed that by fabricating nanofluidic channels with hydrophobic materials, the measured amplitudes of both electroosmotic flow (EOF) and ionic current deviated significantly from the conventional electrokinetic modeling indication. Among these unexpected observations, the complicated dependence of EOF on the surface charge concentration of the channel wall remains most confusing. In this work we give a complete and unified picture for the phenomena by outlining the competing two mechanisms in the water-depletion layer around the channel wall: the decreasing trend of fluidic flow due to the redistribution of net charges, and the increasing trend because of the reduced solution viscosity there. Our quantitative evaluation illustrates that the alternate dominating by the two mechanisms leads to the observed transport behaviors. Furthermore, by considering the decreasing of ionic mobility in the depletion layer, our calculations show quantitative agreement with the latest experiments using BN nanotube channels.

[MicroRNAs in the regulation of brown adipocyte differentiation].

MicroRNAs (miRNAs), a class of endogenous non-coding RNA about 22 nucleotide long, regulate gene expression at the post-transcription level by inhibiting the translation or inducing the degradation of their target mRNAs in organisms. There are two types of adipose tissues: brown and white. White adipose tissues store energy in the form of triglycerides (TGs), while brown adipose tissues catabolize TGs to generate energy. Brown adipose tissues are of great importance to the research of obesity and related metabolic diseases due to their function of preventing people from obesity. A lot of studies have revealed that miRNAs play crucial roles in regulating brown adipocyte differentiation and are modulated by lots of transcription factors and environmental factors, which form a complex regulatory network maintaining the homeostasis of adipose tissues. In this review, we summarize the latest studies of miRNAs in brown adipocyte differentiation, which might provide new strategies for the treatment of obesity and other related diseases.

Achieving High-Performance Lithium-Sulfur Batteries by Modulating Li+ Desolvation Barrier with Liquid Crystal Polymers.

Lithium-sulfur (Li-S) batteries offer high theoretical capacity but are hindered by poor rate capability and cycling stability due to sluggish Li2S precipitation kinetics. Here a sulfonate-group-rich liquid crystal polymer (poly-2,2'-disulfonyl-4,4'-benzidine terephthalamide, PBDT) is designed and fabricated to accelerate Li2S precipitation by promoting the desolvation of Li+ from electrolyte. PBDT-modified separators are employed to assemble Li-S batteries, which deliver a remarkable rate capacity (761 mAh g-1 at 4 C) and cycling stability (500 cycles with an average decay rate of 0.088% per cycle at 0.5 C). A PBDT-based pouch cell even delivers an exceptional capacity of ≈1400 mAh g-1 and an areal capacity of ≈11 mAh cm-2 under lean-electrolyte and high-sulfur-loading condition, demonstrating promise for practical applications. Results of Raman spectra, molecular dynamic (MD) and density functional theory (DFT) calculations reveal that the abundant anionic sulfonate groups of PBDT aid in Li+ desolvation by attenuating Li+-solvent interactions and lowering the desolvation energy barrier. Plus, the polysulfide adsorption/catalysis is also excluded via electrostatic repulsion. This work elucidates the critical impact of Li+ desolvation on Li-S batteries and provides a new design direction for advanced Li-S batteries.

Smoking behavior associated upregulation of SERPINB12 promotes proliferation and metastasis via activating WNT signaling in NSCLC.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of morality among all malignant tumors. Smoking is one of the most important causes of NSCLC, which contributes not only to the initiation of NSCLC but also to its progression. The identification of specific biomarkers associated with smoking will promote diagnosis and treatment. METHODS: Data mining was used to identify the smoking associated gene SERPINB12. CCK8 assays, colony formation assays, a mouse xenograft model and transwell assays were performed to measure the biological functions of SERPINB12 in NSCLC. GSEA, luciferase reporter assays and immunofluorescence were conducted to explore the potential molecular mechanisms of SERPINB12 in NSCLC. RESULTS: In this study, by data mining the TCGA database, we found that SERPINB12 was greatly upregulated in NSCLC patients with cigarette consumption behavior, while the expression level was positively correlated with disease grade and poor prognosis. SERPINB12 is a kind of serpin peptidase inhibitor, but its function in malignant tumors remains largely unknown. Functionally, knockdown of SERPINB12 observably inhibited the proliferation and metastasis of NSCLC cells in vitro and in vivo. Moreover, downregulation of SERPINB12 attenuated Wnt signaling by inhibiting the nuclear translocation of ß-catenin, which explained the molecular mechanism underlying tumor progression. CONCLUSIONS: In conclusion, SERPINB12 functions as a tumorigenesis factor, which could be a promising biomarker for NSCLC patients with smoking behavior, as well as a therapeutic target.

Self-Rectifying Memristors for Three-Dimensional In-Memory Computing.

Costly data movement in terms of time and energy in traditional von Neumann systems is exacerbated by emerging information technologies related to artificial intelligence. In-memory computing (IMC) architecture aims to address this problem. Although the IMC hardware prototype represented by a memristor is developed rapidly and performs well, the sneak path issue is a critical and unavoidable challenge prevalent in large-scale and high-density crossbar arrays, particularly in three-dimensional (3D) integration. As a perfect solution to the sneak-path issue, a self-rectifying memristor (SRM) is proposed for 3D integration because of its superior integration density. To date, SRMs have performed well in terms of power consumption (aJ level) and scalability (>102  Mbit). Moreover, SRM-configured 3D integration is considered an ideal hardware platform for 3D IMC. This review focuses on the progress in SRMs and their applications in 3D memory, IMC, neuromorphic computing, and hardware security. The advantages, disadvantages, and optimization strategies of SRMs in diverse application scenarios are illustrated. Challenges posed by physical mechanisms, fabrication processes, and peripheral circuits, as well as potential solutions at the device and system levels, are also discussed.

Role of Interfaces in Solid-State Batteries.

Solid-state batteries (SSBs) are considered as one of the most promising candidates for the next-generation energy-storage technology, because they simultaneously exhibit high safety, high energy density, and wide operating temperature range. The replacement of liquid electrolytes with solid electrolytes produces numerous solid-solid interfaces within the SSBs. A thorough understanding on the roles of these interfaces is indispensable for the rational performance optimization. In this review, the interface issues in the SSBs, including internal buried interfaces within solid electrolytes and composite electrodes, and planar interfaces between electrodes and solid electrolyte separators or current collectors are discussed. The challenges and future directions on the investigation and optimization of these solid-solid interfaces for the production of the SSBs are also assessed.