ASB3 promotes hepatocellular carcinoma progression by mediating DR5 ubiquitination in TRAIL resistance.

Ankyrin-repeat proteins with a suppressor of cytokine signaling box (ASB) proteins belong to the E3 ubiquitin ligase family. 18 ASB members have been identified whose biological functions are mostly unexplored. Here, we discovered that ASB3 was essential for hepatocellular carcinoma (HCC) development and high ASB3 expression predicted poor clinical outcomes. ASB3 silencing induced HCC cell growth arrest and apoptosis in vitro and in vivo. Liver-specific deletion of Asb3 gene suppressed diethylnitrosamine (DEN)-induced liver cancer development. Mechanistically, ASB3 interacted with death receptor 5 (DR5), which promoted ubiquitination and degradation of DR5. We further showed that ASB3 knockdown stabilized DR5 and increased the sensitivity of liver cancer cells to the treatment of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in a DR5-dependent manner in cellular and in animal models. In summary, we demonstrated that ASB3 promoted ubiquitination and degradation of DR5 in HCC, suggesting the potential of targeting ASB3 to HCC treatment and overcome TRAIL resistance.

Polyoxometalates as Potential Artificial Enzymes toward Biological Applications.

Artificial enzymes, as alternatives to natural enzymes, have attracted enormous attention in the fields of catalysis, biosensing, diagnostics, and therapeutics because of their high stability and low cost. Polyoxometalates (POMs), a class of inorganic metal oxides, have recently shown great potential in mimicking enzyme activity due to their well-defined structure, tunable composition, high catalytic efficiency, and easy storage properties. This review focuses on the recent advances in POM-based artificial enzymes. Different types of POMs and their derivatives-based mimetic enzyme functions are covered, as well as the corresponding catalytic mechanisms (where available). An overview of the broad applications of representative POM-based artificial enzymes from biosensing to theragnostic is provided. Insight into the current challenges and the future directions for POMs-based artificial enzymes is discussed.

Directional Activation of Oxygen by the Au-Loaded ZnAl-LDH with Defect Structure for Highly Efficient Photocatalytic Oxidative Coupling of Methane.

Photocatalytic oxidative coupling of CH4 (OCM) is a promising CH4 conversion process that can achieve efficient methane conversion with the assistance of O2. It remains to be highly challenging to improve the photocatalytic OCM activity from catalyst design and to deepen the understanding of the reactant activation in the OCM process. In this work, the Au-loaded ZnAl-layered double hydroxides (LDHs) with and without oxygen vacancy are constructed (denoted as Au/ZnAl and Au/ZnAl-v), respectively. When applied for photocatalytic OCM, the Au/ZnAl-v shows a CH4 conversion rate of 8.5 mmol g-1 h-1 with 92% selectivity of C2H6 at 40 °C, outperforming most reported photocatalytic OCM systems at low temperature reported in the literature. Furthermore, the catalytic performance of Au/ZnAl-v can be stable for 100 h. In contrast, the An/ZnAl exhibits a CH4 conversion rate of 0.8 mmol g-1 h-1 with 46% selectivity of C2H6. Detailed characterizations and DFT calculation studies reveal that the introduced Ov sites on Au/ZnAl-v are able to activate O2, and the resulting superoxide radical O2·- greatly promotes the activation of CH4. The coupling of CH3· groups with the assistance of Au cocatalyst leads to the formation of C2H6 with high photocatalytic activity.

Ultrathin NiV Layered Double Hydroxide for Methanol Electrooxidation: Understanding the Proton Detachment Kinetics and Methanol Dehydrogenation Oxidation.

Electrochemical methanol oxidation reaction (MOR) is regarded as a promising pathway to obtain value-added chemicals and drive cathodic H2 production, while the rational design of catalyst and in-depth understanding of the structure-activity relationship remains challenging. Herein, the ultrathin NiV-LDH (u-NiV-LDH) with abundant defects is successfully synthesized, and the defect-enriched structure is finely determined by X-ray adsorption fine structure etc. When applied for MOR, the as-prepared u-NiV-LDH presents a low potential of 1.41 V versus RHE at 100 mA cm-2, which is much lower than that of bulk NiV-LDH (1.75 V vs RHE) at the same current density. The yield of H2 and formate is 98.2% and 88.1% as its initial over five cycles and the ultrathin structure of u-NiV-LDH can be well maintained. Various operando experiments and theoretical calculations prove that the few-layer stacking structure makes u-NiV-LDH free from the interlayer hydrogen diffusion process and the hydrogen can be directly detached from LDH laminate. Moreover, the abundant surface defects upshift the d-band center of u-NiV-LDH and endow a higher local methanol concentration, resulting in an accelerated dehydrogenation kinetics on u-NiV-LDH. The synergy of the proton detachment from the laminate and the methanol dehydrogenation oxidation contributes to the excellent MOR performance of u-NiV-LDH.

NF-κB modifies the mammalian circadian clock through interaction with the core clock protein BMAL1.

In mammals, the circadian clock coordinates cell physiological processes including inflammation. Recent studies suggested a crosstalk between these two pathways. However, the mechanism of how inflammation affects the clock is not well understood. Here, we investigated the role of the proinflammatory transcription factor NF-κB in regulating clock function. Using a combination of genetic and pharmacological approaches, we show that perturbation of the canonical NF-κB subunit RELA in the human U2OS cellular model altered core clock gene expression. While RELA activation shortened period length and dampened amplitude, its inhibition lengthened period length and caused amplitude phenotypes. NF-κB perturbation also altered circadian rhythms in the master suprachiasmatic nucleus (SCN) clock and locomotor activity behavior under different light/dark conditions. We show that RELA, like the clock repressor CRY1, repressed the transcriptional activity of BMAL1/CLOCK at the circadian E-box cis-element. Biochemical and biophysical analysis showed that RELA binds to the transactivation domain of BMAL1. These data support a model in which NF-kB competes with CRY1 and coactivator CBP/p300 for BMAL1 binding to affect circadian transcription. This is further supported by chromatin immunoprecipitation analysis showing that binding of RELA, BMAL1 and CLOCK converges on the E-boxes of clock genes. Taken together, these data support a significant role for NF-κB in directly regulating the circadian clock and highlight mutual regulation between the circadian and inflammatory pathways.

A 9-10-Bit Adjustable and Energy-Efficient Switching Scheme for Successive Approximation Register Analog-to-Digital Converter with One Least Significant Bit Common-Mode Voltage Variation.

A 9-10-bit adjustable and energy-efficient switching scheme for SAR ADC with one-LSB common-mode voltage variation is proposed. Based on capacitor-splitting technology and common-mode conversion techniques, the proposed switching scheme reduces the DAC switching energy by 96.41% compared to the conventional scheme. The low complexity and the one-LSB common-mode voltage offset of this scheme benefit from the simultaneous switching of the reference voltages of the capacitors corresponding to the positive array and the negative array throughout the entire reference voltage switching process, and the reference voltage of each capacitor in the scheme does not change more than two voltages. The post-layout result shows that the ADC achieves the 54.96 dB SNDR, the 61.73 dB SFDR, and the 0.67 µw power consumption with the 10-bit mode and the 48.33 dB SNDR, the 54.17 dB SFDR, and the 0.47 µw power consumption with the 9-bit mode in a 180 nm process with a 100 kS/s sampling frequency.

[Study on mechanism of Chinese Yam polysaccharide synergizing nucleoside analogues against hepatitis B virus through p38 MAPK signaling pathway].

This study explore the molecular mechanism of the synergistic effect of Chinese Yam polysaccharides and nucleoside analogues(NAs) on hepatitis B virus(HBV) resistance. Different concentrations of Chinese Yam polysaccharide and entecavir were ad-ded to HepG2.2.15 cells. After the cytotoxicity was detected by cell counting kit-8(CCK-8), the optimal concentration and time of the two drugs to inhibit HepG2.2.15 cells were screened out. They were divided into control group, Chinese Yam polysaccharide group, entecavir group and combination drug group(Chinese Yam polysaccharide + entecavir). The drugs were added to HepG2.2.15 cells, ELISA was used to detect the effects of each group of drugs on the secretion of hepatitis B virus surface antigen(HBsAg) and hepatitis B virus e antigen(HBeAg) in cell supernatant, probe quantitative real-time PCR(probe qRT-PCR) was used to detect the effects of drugs on HBV-DNA in HepG2.2.15 cells, and Western blot was used to detect the effects of each group of drugs on the expression of p38 MAPK, p-p38 MAPK, NTCP proteins in HepG2.2.15 cells. The qRT-PCR was used to detect the effect of drugs on the expression of p38 MAPK and NTCP mRNA in HepG2.2.15 cells. The results showed that compared with control group, the concentrations of HBeAg and HBsAg in Chinese Yam polysaccharide group, entecavir group and combination group decreased(P<0.01 or P<0.001), and both of them inhibited HBV-DNA in HepG2.2.15 cells(P<0.01), and the HBV-DNA inhibition of HepG2.2.15 cells in the combination group was more obvious(P<0.001), and the protein expression levels of p-p38 MAPK and NTCP were significantly decreased(P<0.05 or P<0.01), the mRNA expression level of p38 MAPK increased, and the mRNA expression level of NTCP decreased(P<0.05 or P<0.01). To sum up, Chinese Yam polysaccharide can reduce the expression of NTCP protein and mRNA through p38 MAPK signaling pathway and cooperate with entecavir in anti-HBV.

Structural Transformation in a Sulfurized Polymer Cathode to Enable Long-Life Rechargeable Lithium-Sulfur Batteries.

Sulfurized polyacrylonitrile (SPAN) represents a class of sulfur-bonded polymers, which have shown thousands of stable cycles as a cathode in lithium-sulfur batteries. However, the exact molecular structure and its electrochemical reaction mechanism remain unclear. Most significantly, SPAN shows an over 25% 1st cycle irreversible capacity loss before exhibiting perfect reversibility for subsequent cycles. Here, with a SPAN thin-film platform and an array of analytical tools, we show that the SPAN capacity loss is associated with intramolecular dehydrogenation along with the loss of sulfur. This results in an increase in the aromaticity of the structure, which is corroborated by a >100× increase in electronic conductivity. We also discovered that the conductive carbon additive in the cathode is instrumental in driving the reaction to completion. Based on the proposed mechanism, we have developed a synthesis procedure to eliminate more than 50% of the irreversible capacity loss. Our insights into the reaction mechanism provide a blueprint for the design of high-performance sulfurized polymer cathode materials.

Photocatalytic Oxidative Coupling of Ethane to n-Butane Using CO2 as a Soft Oxidant over NiTi-Layered Double Hydroxide.

Selective conversion of ethane (C2 H6 ) to high-value-added chemicals is a very important chemical process, yet it remains challenging owing to the difficulty of ethane activation. Here, a NiTi-layered double hydroxide (NiTi-LDH) photocatalyst is reported for oxidative coupling of ethane to n-butane (n-C4 H10 ) by using CO2 as an oxidant. Remarkably, the as-prepared NiTi-LDH exhibits a high selectivity for n-C4 H10 (92.35%) with a production rate of 62.06 µmol g-1 h-1 when the feed gas (CO2 /C2 H6 ) ratio is 2:8. The X-ray absorption fine structure (XAFS) and photoelectron characterizations demonstrate that NiTi-LDH possesses rich vacancies and high electron-hole separation efficiency, which can promote the coupling of C2 H6 to n-C4 H10 . More importantly, density functional theory (DFT) calculations reveal that ethane is first activated on the oxygen vacancies of the catalyst surface, and the C─C coupling pathway is more favorable than the C─H cleavage to C2 H4 or CH4 , resulting in the high production rate and selectivity for n-C4 H10 .

Revealing the Kinetic Balance between Proton-Feeding and Hydrogenation in CO2 Electroreduction.

Electrocatalytic reduction of CO2 to high-value-added chemicals provides a feasible path for global carbon balance. Herein, the fabrication of NiNP x @NiSA y -NG (x,y = 1, 2, 3; NG = nitrogen-doped graphite) is reported, in which Ni single atom sites (NiSA ) and Ni nanoparticles (NiNP ) coexist. These NiNP x @NiSA y -NG presented a volcano-like trend for maximum CO Faradaic efficiency (FECO ) with the highest point at NiNP2 @NiSA2 -NG in CO2 RR. NiNP2 @NiSA2 -NG exhibited ≈98% of maximum FECO and a large current density of -264 mA cm-2 at -0.98 V (vs. RHE) in the flow cell. In situ experiment and density functional theory (DFT) calculations confirmed that the proper content of NiSA and NiNP balanced kinetic between proton-feeding and CO2 hydrogenation. The NiNP in NiNP2 @NiSA2 -NG promoted the formation of H* and reduced the energy barrier of *CO2 hydrogenation to *COOH, and CO desorption can be efficiently facilitated by NiSA sites, thereby resulting in enhanced CO2 RR performance.

Insight into the Mechanism of Cd2+ Removal by MgAl Layered Double Hydroxides with Different Host-Guest Interactions.

Layered double hydroxides (LDHs) have shown great potential as adsorbents for the removal of heavy metals. Nevertheless, how the host-guest interactions of LDHs affect the removal mechanism remains to be less explored. Herein, CO3 2- /NO3 - /SO4 2- /Cl- intercalated MgAl-LDHs with different host-guest interactions were fabricated and their removal mechanism for Cd2+ was investigated. The removal capacity increased in the order of MgAl-CO3 (127.3 mg/g)

Influence of optical surface distortion in a cylindrical Offner stretcher on the far-field signal-to-noise ratio.

In a stretcher, the surface distortion of the optical elements can introduce spectral phase modulations into the laser, which can affect the laser's signal-to-noise ratio. In this paper, by combining ray tracing methods and angular spectrum diffraction methods, the impact of the mid-frequency surface distortion of the optical elements in an cylindrical Offner stretcher on the far-field signal-to-noise ratio of the laser is simulated. The results show that reducing the spatial chirp on the convex cylindrical mirror can effectively improve the far-field signal-to-noise ratio of the laser, and two methods to improve the far-field signal-to-noise ratio are presented.

High energy and low noise soliton fiber laser comb based on nonlinear merging of Kelly sidebands.

Optical solitons in mode-locked laser cavities with dispersion-nonlinearity interaction, delivers pulses of light that retain their shape. Due to the nature of discretely distributed dispersion and nonlinearity, optical solitons can emit Kelly-sidebands via the frequency coupling of soliton and dispersive waves. In this paper, we generate a high-energy femtosecond laser comb, by using the intracavity Kelly radiations and 3rd order nonlinearities. By increasing the intracavity power, the soliton envelop and the Kelly-sidebands merge together via four-wave-mixing, forming a super-continuum spectrum, obtaining 3.18 nJ pulse energy. A supercontinuum span covering from 1100 nm to 2300 nm for further self-referenced f-2f stabilization can be directly achieved by using an amplification-free external supercontinuum technique. Our finding not only demonstrates a non-trivial frequency-time evolution based on 'erbium + χ(3)' nonlinear gains, but also offers a new opportunity to develop practically compact fiber frequency combs for frequency metrology or spectroscopy.

Degradation of malathion and carbosulfan by ozone water and analysis of their by-products.

BACKGROUND: Treatment by ozone water is an emerging technology for the degradation of pesticide residues in vegetables. The ozone dissolved in water generates hydroxyl radicals (· OH), which are highly effective in decomposing organic substances, such as malathion and carbosulfan. RESULTS: We found that washing pak choi with 2.0 mg L-1 ozone water for 30 min resulted in 58.3% and 38.2% degradation of the malathion and carbosulfan contents respectively, and the degradation rates of these pure pesticides were 83.0% and 66.3% respectively. In addition, the 'first + first'-order reaction kinetic model was found to predict the trend in the pesticide content during ozone water treatment. Based on investigations by gas chromatography-mass spectrometry combined with the structures of the pesticides, the by-products generated were identified. More specifically, the ozonation-based degradation of carbosulfan generated carbofuran and benzofuranol, whereas malathion produced succinic acid and phosphoric acid. Although some new harmful compounds were formed during degradation of the parent pesticides, these were only present in trace quantities and were transient intermediates that eventually disappeared during the reaction. CONCLUSION: Our results, therefore, indicate that ozone water treatment technology for pesticide residue degradation is worthy of popularization and application. © 2022 Society of Chemical Industry.

Evaluation of the effectiveness of comprehensive drug price reform: a case study from Shihezi city in Western China.

BACKGROUND: China carried out a comprehensive drug price reform (CDPR) in 2017 to control the growing expense of drug effectively and reduce the financial burden of inpatients. However, early studies in pilot regions found the heterogeneity in the effectiveness of CDPR from different regions and other negative effects. This study aimed to evaluate the effects of the reform on medical expenses, medical service utilisation and government financial reimbursement for inpatients in economically weaker regions. METHODS: Shihezi was selected as the sample city, and 238,620 inpatients, who were covered by basic medical insurance (BMI) and had complete information from September 2016 to August 2018 in public hospitals, were extracted by cluster sampling. An interrupted series design was used to compare the changing trends in medical expenses, medical service utilisation and reimbursement of BMI for inpatients before and after the reform. RESULTS: Compared with the baseline trends before the CDPR, those after the CDPR were observed with decreased per capita hospitalisation expenses (HE) by ¥301.9 per month (p < 0.001), decreased drug expense (DE) ratio at a rate of 0.32% per month (p < 0.05) and increased ratio of diagnosis and treatment expenses (DTE) at a rate of 0.25% per month (p < 0.01). The number of inpatients in secondary and tertiary hospitals declined by 458 (p < 0.001) and 257 (p < 0.05) per month, respectively. The BMI reimbursement in tertiary hospitals decreased by ¥254.7 per month (p < 0.001). CONCLUSION: The CDPR controlled the increase in medical expenses effectively and adjusted its structure reasonably. However, it also reduced the medical service utilisation of inpatients in secondary and tertiary hospitals and financial reimbursement for inpatients in tertiary hospitals.

The clinical study of fast-track rehabilitation nursing in the perioperative period of therapeutic laparoscopy of colon cancer patients.

OBJECTIVE: To explore the clinical application of fast-track rehabilitation nursing in the perioperative period of therapeutic laparoscopy of colon cancer patients. METHODS: Patients with colorectal cancers who were hospitalized in the Department of Oncology and General Surgery of The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University from August 2016 to December 2018 were selected as the research subjects of the study. All the research subjects were divided into the study group 1(n=29), the study group 2(n=29) and the control group (n=24). The control group received routine nursing during the perioperative period, and the research group 1 and 2 received rapid rehabilitation nursing during the perioperative period. Postoperative comparison was made between the two groups on the differences in the time of the first time out of bed, the time of the first anal exhaust, and the time of the first feeding. The differences of pain control in each group after nursing care were evaluated by the pain scale, and the degree of satisfaction of each group was evaluated by the satisfaction scale. RESULTS: In terms of the basic information of patients, the experimental results had indicated no significant statistical difference among the study group 1, the study group 2, and the control group (P>0.05). By analysing the postoperative physical condition indicators of patients, the time of first off-bed activity, the time of first anal exhaust, and the first time of food intake of patients in the observation group 1 and the observation group 2 were significantly different (P<0.05) as compared with the control group. Besides that, the postoperative pain scale and pain satisfaction of patients were observed, in which the difference in pain scales at each 6h, 12h, 24h, and 48h after the surgeries were statistically significant (P<0.05). In terms of the satisfaction of pain control or pain relief, the differences were statistically significant (P<0.05). CONCLUSIONS: Therefore, it was concluded that the fast-track rehabilitation nursing could promote the treatment of colon cancer patients. Despite the deficiencies of the experimental processes, the study has provided the good results on fast-track rehabilitation nursing with a reliable theoretical basis.

LINC02273 drives breast cancer metastasis by epigenetically increasing AGR2 transcription.

BACKGROUND: The majority of breast cancer patients die of metastasis rather than primary tumors, whereas the molecular mechanisms orchestrating cancer metastasis remains poorly understood. Long noncoding RNAs (lncRNA) have been shown to regulate cancer occurrence and progression. However, the lncRNAs that drive metastasis in cancer patients and their underlying mechanisms are still largely unknown. METHODS: lncRNAs highly expressed in metastatic lymph nodes were identified by microarray. Survival analysis were made by Kaplan-Meier method. Cell proliferation, migration, and invasion assay was performed to confirm the phenotype of LINC02273. Tail vein model and mammary fat pad model were used for in vivo study. RNA pull-down and RIP assay were used to confirm the interaction of hnRNPL and LINC02273. Chromatin isolation by RNA purification followed by sequencing (ChIRP-seq), RNA-seq, ChIP-seq, and luciferase reporter assay reveal hnRNPL-LINC02273 regulates AGR2. Antisense oligonucleotides were used for in vivo treatment. RESULTS: We identified a novel long noncoding RNA LINC02273, whose expression was significantly elevated in metastatic lesions compared to the primary tumors, by genetic screen of matched tumor samples. Increased LINC02273 promoted breast cancer metastasis in vitro and in vivo. We further showed that LINC02273 was stabilized by hnRNPL, a protein increased in metastatic lesions, in breast cancer cells. Mechanistically, hnRNPL-LINC02273 formed a complex which activated AGR2 transcription and promoted cancer metastasis. The recruitment of hnRNPL-LINC02273 complex to AGR2 promoter region epigenetically upregulated AGR2 by augmenting local H3K4me3 and H3K27ac levels. Combination of AGR2 and LINC02273 was an independent prognostic factor for predicting breast cancer patient survival. Moreover, our data revealed that LINC02273-targeting antisense oligonucleotides (ASO) substantially inhibited breast cancer metastasis in vivo. CONCLUSIONS: Our findings uncover a key role of LINC02273-hnRNPL-AGR2 axis in breast cancer metastasis and provide potential novel therapeutic targets for metastatic breast cancer intervention.

MiR-181 family-specific behavior in different cancers: a meta-analysis view.

The involvement of microRNAs in malignant transformation and cancer progression was previously grounded. The observations made by multiple published studies led to the conclusion that some of these small sequences could be eventually used as biomarkers for diagnosis/prognosis. This meta-analysis investigated whether microRNA-181 family members could predict the outcome of patients carrying different types of cancer. We searched the PubMed and Embase databases for studies evaluating the expression levels of miR-181a/b/c/d in patients with cancer, selecting the publications that assessed the relation between low and high levels of one of these four microRNAs and patients' outcome. Hazard ratios (HRs) or risk ratios (RRs) were extracted from the studies, and random-effect model was performed to investigate the role of miR-181 in the outcome of these patients. The meta-analysis comprised 26 studies including 2653 cancer patients from 6 countries. The results showed significant association between the expression of miR-181 family members and colorectal cancer. Considering the heterogeneity of the pathologies, the analysis, including all types of cancer and the expression of all the miR-181 family members together, showed no association with distinct outcome (HR = 1.099, p = 0.435). When the analysis was performed on each microRNA separately, the expression of miR-181c was significantly associated with the outcome of patients with cancer (HR = 2.356, p = 0.011) and miR-181a expression levels significantly correlated with survival in patients with non-small-cell lung cancer (HR = 0.177, p < 0.05). This meta-analysis revealed evidence regarding the involvement of miR-181 family members in the outcome of patients with some types of cancer, according to their expression level.

Casticin inhibits nasopharyngeal carcinoma growth by targeting phosphoinositide 3-kinase.

BACKGROUND: Casticin, an isoflavone compound extracted from the herb Fructus Viticis, has demonstrated anti-inflammatory and anticancer activities and properties. The aim of this study was to investigate the effects and mechanisms of casticin in nasopharyngeal carcinoma (NPC) cells and to determine its potential for targeted use as a medicine. METHODS: NPC cells were used to perform the experiments. The CCK­8 assay and colony formation assays were used to assess cell viability. Flow cytometry was used to measure the cell cycle and apoptosis analysis (annexin V/PI assay). A three-dimensional (3D) tumour sphere culture system was used to characterize the effect of casticin on NPC stem cells. In silico molecular docking prediction and high-throughput KINOME scan assays were used to evaluate the binding of casticin to phosphoinositide 3-kinase (PI3K), including wild-type and most of mutants variants. We also used the SelectScreen assay to detect the IC50 of ATP activity in the active site of the target kinase. Western blotting was used to evaluate the changes in key proteins involved cell cycle, apoptosis, stemness, and PI3K/protein kinase B (AKT) signalling. The effect of casticin treatment in vivo was determined by using a xenograft mouse model. RESULTS: Our results indicate that casticin is a new and novel selective PI3K inhibitor that can significantly inhibit NPC proliferation and that it induces G2/GM arrest and apoptosis by upregulating Bax/BCL2 expression. Moreover, casticin was observed to affect the self-renewal ability of the nasopharyngeal carcinoma cell lines, and a combination of casticin with BYL719 was observed to induce a decrease in the level of the phosphorylation of mTORC1 downstream targets in BYL719-insensitive NPC cell lines. CONCLUSION: Casticin is a newly emerging selective PI3K inhibitor with potential for use as a targeted therapeutic treatment for nasopharyngeal carcinoma. Accordingly, casticin might represent a novel and effective agent against NPC and likely has high potential for combined use with pharmacological agents targeting PI3K/AKT.

Brain-Machine Interface-Based Rat-Robot Behavior Control.

Brain-machine interface (BMI) provides a bidirectional pathway between the brain and external facilities. The machine-to-brain pathway makes it possible to send artificial information back into the biological brain, interfering neural activities and generating sensations. The idea of the BMI-assisted bio-robotic animal system is accomplished by stimulations on specific sites of the nervous system. With the technology of BMI, animals' locomotion behavior can be precisely controlled as robots, which made the animal turning into bio-robot. In this chapter, we reviewed our lab works focused on rat-robot navigation. The principles of rat-robot system have been briefly described first, including the target brain sites chosen for locomotion control and the design of remote control system. Some methodological advances made by optogenetic technologies for better modulation control have then been introduced. Besides, we also introduced our implementation of "mind-controlled" rat navigation system. Moreover, we have presented our efforts made on combining biological intelligence with artificial intelligence, with developments of automatic control and training system assisted with images or voices inputs. We concluded this chapter by discussing further developments to acquire environmental information as well as promising applications with write-in BMIs.