Search

C/SiBCN composites with a density of 1.64 g/cm 3 were prepared via precursor infiltration and pyrolysis and the bending strength and modulus at room temperature was 305 MPa and 53.5 GPa. The precursor derived SiBCN ceramics showed good thermal stability at 1600 °C and the SiC and Si 3 N 4 crystals appeared above 1700 °C. The bending strength of the composites was 180 MPa after heat treatment at 1500 °C, and maintained at 40 MPa-50 MPa after heat treatment for 2 h at 1600 °C-1900 °C. In C/SiBCN composites, SiBCN matrix could retain amorphous up to 1500 °C and SiC grains appeared at 1600 °C but without Si 3 N 4 . The reason for no detection of Si 3 N 4 was that the carbon fiber reacted with Si 3 N 4 to form an interface layer (composed of SiC and unreacted C) and a polycrystalline transition layer (composed of B and C elements), leading to the degradation of the mechanical properties.

Sex determining region Y (SRY)-related high-mobility group (HMG) box (SOX) factors belong to an evolutionarily conserved family of transcription factors that play essential roles in cell fate decisions involving numerous developmental processes. In recent years, the significance of SOX factors in the initiation and progression of cancers has been gradually revealed, and they act as potential therapeutic targets for cancer. However, the research involving SOX factors is still preliminary, given that their effects in some leading-edge fields such as tumor immune microenvironment (TIME) remain obscure. More importantly, as a class of ‘undruggable’ molecules, targeting SOX factors still face considerable challenges in achieving clinical translation. Here, we mainly focus on the roles and regulatory mechanisms of SOX family members in hepatocellular carcinoma (HCC), one of the fatal human health burdens worldwide. We then detail the role of SOX members in remodeling TIME and analyze the association between SOX members and immune components in HCC for the first time. In addition, we emphasize several alternative strategies involved in the translational advances of SOX members in cancer. Finally, we discuss the alternative strategies of targeting SOX family for cancer and propose the opportunities and challenges they face based on the current accumulated studies and our understanding.

Voice assistants can be manipulated by various malicious voice commands, yet existing attacks require a nearby speaker to play the attack commands. In this paper, we show that even when no speakers are available, we can play malicious commands by utilizing the capacitors inside electronic devices, i.e., we convert capacitors into speakers and call it CapSpeaker. Essentially, capacitors can emit acoustic noises due to the inverse piezoelectric effect, i.e., varying the voltage across a capacitor can make it vibrate and thus emit acoustic noises. Forcing capacitors to play malicious voice commands is challenging because (1) the frequency responses of capacitors as speakers have poor performance in the range of audible voices, and (2) we have no direct control over the voltage across capacitors to manipulate their emitting sounds. To overcome the challenges, we use a PWM-based modulation scheme to embed the malicious audio onto a high-frequency carrier, e.g., above 20 kHz, and we create malware that can induce the right voltage across the capacitors such that CapSpeaker plays the chosen malicious commands. We conducted extensive experiments with 2 LED lamps (a modified one and a commercial one) and 5 victim devices (iPhone 4s, iPad mini 5, Huawei Nova 5i, etc.). Evaluation results demonstrate that CapSpeaker is feasible at a distance up to 10.5 cm, triggering a smartphone to receive voice commands, e.g., "open the door''.

Abstract: Cannabinoids are compounds that were initially isolated from cannabis marihuana and are also widely present in both nervous and immune systems of animals. In recent years, with in-depth research on cannabinoids, their clinical medicinal value has been evaluated, and many exciting achievements have been continuously accumulating, especially in the field of neurodegenerative disease. Alzheimer's disease is the most common type of neurodegenerative disease that causes dementia and has become a global health problem that seriously impacts human health today. In this review, we discuss the therapeutic potential of cannabinoids for the treatment of Alzheimer’s disease. How cannabinoids act on different endocannabinoid receptor subtypes to regulate Alzheimer’s disease, the roles of the endocannabinoid system in Alzheimer’s disease are outlined, and the underlying mechanisms are discussed. Finally, we summarize the most relevant opportunities of cannabinoid pharmacology related to Alzheimer’s disease and discuss the potential usefulness of cannabinoids in the clinical treatment of Alzheimer’s disease.

The effect of targeted therapy for metastatic hepatocellular carcinoma (HCC) is still unsatisfactory. Exploring the underlying mechanism of HCC metastasis is favorable to provide new therapeutic strategies. T-box (TBX) transcription factor family genes, which are crucial regulators in embryo and organ development, are vital for regulating tumor initiation, growth and metastasis. Here we explored the role of TBX19 in HCC metastasis, which is one of the most upregulated TBX family genes in human HCC tissues. TBX19 expression was markedly upregulated in HCC tissues and elevated TBX19 expression predicted poor prognosis. Overexpression of TBX19 enhanced HCC metastasis through upregulating epidermal growth factor receptor (EGFR) and Rac family small GTPase 1 (RAC1) expression. Downregulation of EGFR and RAC1 inhibited TBX19-mediated HCC metastasis, while upregulation of EGFR and RAC1 restored inhibition of HCC metastasis mediated by TBX19 knockdown. Furthermore, epidermal growth factor (EGF)/EGFR signaling upregulated TBX19 expression via the extracellular signal-regulated kinase (ERK)/nuclear factor (NF)-kB axis. Besides, the combined application of EGFR inhibitor Erlotinib and RAC1 inhibitor NSC23766 markedly inhibited TBX19-mediated HCC metastasis. In HCC cohorts, TBX19 expression was positively associated with EGFR and RAC1 expression. Patients with positive coexpression of TBX19/EGFR or TBX19/RAC1 displayed the poorest prognosis. In conclusion, EGF/EGFR signaling upregulated TBX19 expression via ERK/NF-kB pathway and TBX19 fostered HCC metastasis by enhancing EGFR and RAC1 expression, which formed an EGF-TBX19-EGFR positive feedback loop. Targeting this signaling pathway may offer a potential therapeutic strategy to efficiently restrain TBX19-mediated HCC metastasis.

Carboxylesterase (CES) plays an essential role in the hydrolysis of ester prodrugs. Our study explored the inhibitions of Radix Scutellariae flavones, including baicalein (B), baicalin (BG), wogonin (W), wogonoside (WG), oroxylin A (OXA) and oroxylin A-7-O-glucuronide (OAG), on CES-mediated hydrolysis of seven prodrugs (capecitabine, clopidogrel, mycophenolate mofetil, dabigatran etexilate, acetylsalicylic acid, prasugrel and irinotecan).In vitro screenings were developed by incubating the flavones with prodrugs in rat plasma, intestine S9 and liver S9. Docking simulations were conducted using AMDock v1.5.2. In vivo evaluations were performed in rats co-administered with the selected flavone and prodrug via oral gavage/intravenous administration for five consecutive days.The in vitro investigation showed that B and OXA demonstrated strongest inhibitions on the hydrolysis of irinotecan followed by dabigatran in rat plasma, intestine S9 and liver S9. Consistent results showed in the molecular docking analyses. Additionally, in rats receiving irinotecan, B/OXA intravenous and oral pre-treatments both led to reduction trends on the active metabolite SN-38 formation in plasma. Besides, significant decreases of SN-38/irinotecan plasma concentration ratios were found in the B/OXA oral pre-treatment group with quicker and stronger inhibition potential in OXA pre-treatment than that from B pre-treatment. OXA oral pre-treatment was also found to be able to significantly inhibit intestinal CES2 activities at 0.5 h and 5 h after irinotecan administration.Our current findings for the first time alert on potential CES-mediated HDIs between RS flavones and prodrugs, which provide a constructive information referring to rational drug combinations in clinical practice.

Objective: Cervical cancer (CC) is one of the most common types of malignant female cancer, and its incidence and mortality are not optimistic. Protein panels can be a powerful prognostic factor for many types of cancer. The purpose of our study was to investigate a proteomic panel to predict survival of patients with common CC. Methods and results: The protein expression and clinicopathological data of CC were downloaded from The Cancer Proteome Atlas (TCPA) and The Cancer Genome Atlas (TCGA) database, respectively. We selected the prognosis-related proteins (PRPs) by univariate Cox regression analysis and found that the results of functional enrichment analysis were mainly related to apoptosis. We used Kaplan–Meier(K-M) analysis and multivariable Cox regression analysis further to screen PRPs to establish a prognostic model, including BCL2, SMAD3, and 4EBP1-pT70. The signature was verified to be independent predictors of OS by Cox regression analysis and the Area Under Curves. Nomogram and subgroup classification were established based on the signature to verify its clinical application. Furthermore, we looked for the co-expressed proteins of three-protein panel as potential prognostic proteins.Conclusion: A proteomic signature independently predicted OS of CC patients, and the predictive ability was better than the clinicopathological characteristics. This signature can help improve prediction for clinical outcome and provides new targets for CC treatment.

Various characteristics of mobile applications (apps) and associated in-app services have been used reveal potentially-sensitive user information; however, privacy concerns have prompted third-party apps to rigorously restrict access to data related to mobile app usage. This paper outlines a novel approach to the extraction of detailed app usage information based on analysis of the electromagnetic (EM) signals emitted from mobile devices when executing app-related tasks. Note that this type of EM leakage becomes high-complex when multiple apps are used simultaneously and is subject to interference from geomagnetic signals generated by device movement. This paper proposes a deep learning-based multi-label classification system to identify apps and in-app services based on magnetometer readings. The proposed MAGTHIEF system uses accelerometer and gyroscope data to cancel out the offset in geomagnetic signals followed by an elaborate deep region convolution neural network (DRCNN) to differentiate among multiple apps and the corresponding inapp services. Experiments on 50 apps demonstrated the efficacy of MAGTHIEF in identifying multiple apps and in-app services, achieving high average macro F1 scores of 0.87 and 0.95, respectively. MAGTHIEF also achieved time duration accuracy of 89.5% in recognizing app trajectory in the real-world scene.

Background and aims Because of a paucity of effective treatment options, metastasis is still a major cause for HCC-associated mortality. The molecular mechanism of inflammation-induced HCC metastasis is open for study. Here, we characterized the function of solute carrier family 7 member 11 (SLC7A11) in inflammation-related HCC metastasis and probed therapy strategies for this subpopulation of patients. Approach and results Elevated expression of SLC7A11 was positively correlated with poor tumor differentiation, and higher tumor-nodule-metastasis stage, and indicated poor prognosis in human HCC. SLC7A11 increased HIF1α expression through reducing α-ketoglutarate (αKG) level by exporting glutamate. SLC7A11 up-regulated programmed death ligand 1 (PD-L1) and colony-stimulating factor 1 (CSF1) expression through αKG-HIF1α cascade. SLC7A11 overexpression in HCC cells promoted intratumoral tumor-associated macrophage (TAM) and myeloid-derived suppressor cell (MDSC) infiltration through the CSF1/colony-stimulating factor 1 receptor (CSF1R) axis, whereas knockdown of CSF1 attenuated SLC7A11-mediated intratumoral TAM and MDSC infiltration and HCC metastasis. Depletion of either TAMs or MDSCs decreased SLC7A11-mediated HCC metastasis. Furthermore, the combination of CSF1R inhibitor BZL945 and anti-PD-L1 antibody blocked SLC7A11-induced HCC metastasis. In addition, IL-1β up-regulated SLC7A11 expression through the interleukin-1 receptor type 1 (IL-1R1)/extracellular signal-regulated kinase/specificity protein 1 pathway. SLC7A11 knockdown impaired IL-1β-promoted HCC metastasis. Anakinra, an IL-1R1 antagonist, reversed IL-1β-promoted HCC metastasis. In human HCC tissues, SLC7A11 expression was positively associated with HIF1α, PD-L1, and CSF1 expression and intratumoral TAM and MDSC infiltration. Conclusions IL-1β-induced SLC7A11 overexpression up-regulated PD-L1 and CSF1 through the αKG/HIF1α axis, which promoted TAM and MDSC infiltration. Interruption of this oncogenic loop may provide a promising therapy strategy for the inhibition of SLC7A11-mediated HCC metastasis.

Trade secrets such as intellectual properties are the inherent values for firms. Although companies have exploited strict access management policies and isolated their networks from the public Internet, trade secrets are still vulnerable to side-channel attacks. Side-channels can reveal the computing processes of computers in forms of various physical signals such as light, electromagnetism, and even heat. Such side-channels can bypass the isolation mechanism and therefore bring about severe threats. However, existing side-channels can only perform well within a short-distance (e.g., less than 1 meter) due to the high attenuation of signals. In this paper, we seek to utilize the built-in power lines in a building and construct a power side-channel that enables remote, i.e., cross-outlet attack against trade secrets. To this end, we investigate the power factor correction (PFC) module inside the power supply units of commodity computers and find that the PFC signals observed from an outlet can precisely reveal the power consumption information of all the connected devices, even from the outlets in adjacent rooms. Based upon this insight, we design and implement OutletSpy, a power side-channel attack that can infer application launching from a remote outlet and therefore enjoys the stealthiness property. We validate and evaluate OutletSpy with a dataset under different background APPs, time variations and different locations. The experiment results show OutletSpy can infer the application launching with 98.25% accuracy.

Reducing the energy consumption and electrode cost for electrochemical recovery of phosphorus (P) from wastewater is crucial for the large-scale application. In this study, biochar electrodes were investigated as the low-cost cathode in a microbial electrolysis cell (MEC) and this P-enriched biochar electrode was directly retrieved as P fertilizer after wastewater treatment. The Fe2+ salt modified biochar significantly increased the electrochemical performance of MECs due to the improved electrical conductivity and cathodic activity. Compared to the pristine biochar cathode, the current density of the MEC increased from 16.8 ± 0.2 A/m3 to 20.7 ± 0.8 A/m3, and the P removal increased from 28.8% ± 1% to 62.4% ± 3.5%. The power consumption was 0.25 ± 0.01 kWh/kg P which was more than one order of magnitude lower than the previous report. It was also demonstrated that the P enriched biochar amended soil improved the Pakchoi cultivation.

The molecular structure of polymer has a great influence on the physical and chemical properties of polysilazane and the properties of ceramics pyrolyzed from the polysilazane. The polysilazane with reticulating molecular structure has good performance generally. The performance of the precursor can be effectively improved by reasonable molecular structure design and control of the synthesis process. In this paper, a reticulating polysilazane PSZ-M with outstanding meltability and solubility were synthesized via an aminolysis reaction between dichloromethylsilane (DCMS) and hexamethyldisilazane (HMDZ), and using the melamine as additive. The properties and the ceramization process of PSZ-M, as well as the molecular structure and properties of derived SiCN ceramic, were well studied. The melamine can be introduced via the dehydrogenation reaction between N–H and Si–H. The ceramics yield was enhanced to 63.18% at 900 °C after the introduction of melamine. The SiCN ceramics derived from the PSZ-M can remain amorphous when pyrolyzed below 1400 °C, the crystal phase of SiC, SiN4 were detected for 1500 °C treated samples. The using of melamine as an additive to synthesis polysilazanes has led to the development of a convenient approach for constructing polysilazanes with reticulating structure and ideal performance, which supports a strategy for the structure design of preceramic polymers.

Background SWELL1 was recently demonstrated to be an indispensable part of the volume-regulated anion channel (VRAC). VRAC is reported to participate in cell proliferation, survival, and migration. However, the correlation between SWELL1 and hepatocellular carcinoma (HCC) remains poorly-understood. In this study, we tried to explore the role of SWELL1 in HCC. Methods Immunohistochemistry and quantitative real-time-PCR (qRT-PCR) was used to measure SWELL1 expression in HCC samples obtained from patients with HCC. The effects of SWELL1 on HCC cell proliferation, apoptosis, and metastasis were analysed by corresponding cytological experiments including Cell Counting Kit-8 (CCK8), colony-forming, 5-ethynyl-2′-deoxyuridine (EdU), cell cycle analysis, TUNEL, Annexin V and PI staining, wound healing, transwell, and so on. BALB/c nude mice were used for the in vivo assays. qRT-PCR and western blotting was performed for molecular mechanisms. Findings SWELL1 was highly expressed in HCC tissues, and related to the poor prognosis. In vitro, the over-expression of SWELL1 significantly induced cell proliferation and migration, and inhibited apoptosis, whereas suppressing SWELL1 had the opposite effects. Moreover, knockdown of SWELL1 suppressed the growth and metastasis of HCC in vivo. Further experiments revealed that SWELL1 induced cell growth by activating the cyclinD1/CDK2 pathway via the connection with PKCa at the signalling level, and regulated cell migration through the JNK pathway in HCC. Interpretation SWELL1 acts as a promoter in the growth and metastasis of HCC cells and may be a potential intervention target for HCC. Fund This work is supported by the National Natural Science Foundation of China (No. 81572422 , 81700515 ).

Chrysanthemum indicum L. is a type of herb that is widely used in China, Korea, and Japan. It has been used as an ingredient in traditional medicines, tea, and functional food because of its various anti-inflammatory and anti-oxidant bioactivities. Such bioactivities have been associated with flavonoids such as apigenin, luteolin and linarin in C. indicum. However, the biosynthesis pathway has not been investigated. In this study, using transcriptomic analysis and targeted metabolic profiling from five different tissues, we characterize the levels of flavonoids and mine the corresponding genes involved in flavonoid biosynthesis. Transcriptomic analysis revealed that 103 unigenes are involved in flavonoid-related biosynthesis pathways. Flavone synthase (FNS) is the key enzyme responsible for flavone synthesis and provides precursors for acacetin and linarin biosynthesis. One putative FNS Ⅱ gene, with the highest Reads Per Kilobase per Million mapped reads (RPKM) in flower and flower bud was cloned. Quantitative real-time polymerase chain reaction (RT-qPCR) revealed that CiFNSⅡ exhibited a similar expression pattern to that in the transcriptome in terms of RPKM. In addition, a targeted metabolic profiling of three flavanones (naringenin, eriodictyol, and liquiritigenin), three flavones (apigenin, luteolin, and 7,4′-dihydroxyflavone), and two flavone derivatives (linarin and acacetin) was performed to characterize the distribution of these flavonoids in different tissues of C. indicum. The recombinant FNSⅡ protein expressed in yeast was able to catalyze the conversion of three flavanones into the respective flavones. Based on the transcriptome analysis, metabolic profiling, and activity assays, a linarin biosynthesis pathway is proposed. Our study provides insight into the potential application of molecular breeding and metabolic engineering for improving the quality of cultivated C. indicum.

On account of the excellent oxidation resistance of precursor-derived SiBCN ceramics, carbon-fiber-reinforced SiBCN (C/SiBCN) composites are increasingly being used in high-temperature aerospace applications. However, very few studies have investigated the high-temperature oxidation behavior of C/SiBCN composites for their application to high-heat engines. Herein, C/SiBCN composites prepared by precursor infiltration and pyrolysis were tested in static air up to an oxidation temperature of 1700 °C. The composites’ structural evolution after oxidation and their potential oxidation mechanisms were investigated in detail. The carbon fibers were preferentially oxidized at temperatures in the range of 1200–1500 °C and completely oxidized at 1500 °C. The oxidation of the fibers at 1500 °C resulted in the formation of abundant oxygen channels and consequently a high oxide scale growth rate of 5–7 μm2 h−1 and a large mass loss of 54.6 wt%. At elevated temperatures in the range of 1600–1700 °C, a dense SiO2 oxide layer was formed by the sacrificial oxidation of the SiBCN matrix. The oxidation rate of the composites was therefore controlled by the diffusion rate of oxygen through the protective SiO2 oxide layer and the weight loss of the composites decreased to 28.6% after oxidation at 1600 °C for 60 min. The structural integrity of the composites was maintained after long-term oxidation at 1600 °C.

Ferroptosis is a newly defined programmed cell death process with the hallmark of the accumulation of iron‐dependent lipid peroxides. The term was first coined in 2012 by the Stockwell Lab, who described a unique type of cell death induced by the small molecules erastin or RSL3. Ferroptosis is distinct from other already established programmed cell death and has unique morphological and bioenergetic features. The physiological role of ferroptosis during development has not been well characterized. However, ferroptosis shows great potentials during the cancer therapy. Great progress has been made in exploring the mechanisms of ferroptosis. In this review, we focus on the molecular mechanisms of ferroptosis, the small molecules functioning in ferroptosis initiation and ferroptosis sensitivity in different cancers. We are also concerned with the new arising questions in this particular research area that remains unanswered.

Due to limited energy supply of Internet of Things (Zhao et al. 2018) (IoT) devices, asynchronous duty cycle radio management is widely adopted to save energy. Since the sleep schedules of nodes are unsynchronized, a sender has to repeatedly send frames to coordinate with its receiver or keep sleeping until the receiver’s wake-up time will come according to receiver’s sleep-wake schedule. In such contexts, opportunistic forwarding, which takes the earliest forwarding opportunity instead of a deterministic forwarder, shows great advantage in utilizing channel resource for duty-cycled IoT networks. The multiple forwarding choices with temporal and spatial diversity increase the chance of collision tolerance in opportunistic forwarding, potentially enhancing the overall performance of duty-cycled multi-hop networks. However, since the current channel contention mechanisms mainly focus on collision avoidance, it is too conservative to exploit concurrency. To address this problem, in this article, we propose COF to fully exploit the potential Concurrency for Opportunistic Forwarding in duty-cycled IoT networks. COF achieves concurrent transmission by: (i) measuring conditional link quality under the interference of on-going transmissions, and then (ii) further modeling the benefit of potential concurrency opportunities. According to the expected benefit of concurrency, COF decides whether or not to transmit in concurrent way. COF also adopts concurrency flag and signal features to avoid data collision caused by disordered concurrent transmissions and enhance the accuracy of conditional link quality estimation. COF can be easily integrated into the conventional unsynchronized and duty-cycled protocols. We have implemented COF and evaluated its performance on a 40-node testbed. The results show that COF can effectively exploit potential concurrency in opportunistic forwarding and COF outperforms the state-of-art protocols under diverse traffic load and network density.

In this paper, the application of ultrafiltration (UF) technology to treat cadmium (Cd) pollution in surface waters is investigated. The effect of the UF membrane molecular weight cut-off (MWCO), Cd ion (Cd2+) concentration, solution pH and ionic strength on the removal, and mass balance of Cd were explored. In addition, the effect of the solution pH on UF membrane fouling was analyzed. The results indicated that UF membranes with a low MWCO resulted in an improved Cd removal rate. In addition, as the Cd2+ concentration in feedwater increased, the Cd removal rate decreased, while the Cd concentration in the permeate increased. Since the solution pH and ionic strength had a notable impact on the Cd removal rate, a high pH value and low ionic strength led to a higher removal rate of Cd. Under optimal Cd removal conditions, UF reduced the influent Cd concentration from 1.0 to 0.019 mg/L. For membrane fouling, increasing the solution pH led to more serious membrane fouling. This phenomenon was the result of Cd2+ reacting with OH− and forming a Cd (OH)2 precipitate. The precipitate and humic acid formed compact cakes on the membrane surface and blocked membrane pores. These results provided adequate evidence for the higher removal of Cd with increasing solution pH. In addition, SEM images under different pH conditions were in agreement with the conclusion mentioned above, which provided further support for the effect of the solution pH on Cd removal and membrane fouling.

Background Growing evidence indicates that high phosphoserine phosphatase (PSPH) expression is associated with tumor prognosis in many types of cancers. However, the role of PSPH in non-small cell lung cancer (NSCLC) is unclear. The purpose of this study was to investigate the clinical significance of PSPH in NSCLC. Methods One hundred forty-three patients with histologically confirmed NSCLC who underwent surgery were included. Quantitative real-time PCR and Western blot were used to assess PSPH expression in paired tumor and corresponding adjacent non-tumorous tissues. The role of PSPH in invasion and cell growth was investigated in vitro. Results Compared to adjacent normal lung tissues, PSPH messenger RNA and protein levels were significantly higher in NSCLC tissues, and the PSPH expression level was positively related to clinical stage, metastasis, and recurrence. High PSPH expression was predictive of poor overall survival. A549 cells transfected with small interfering-PSPH showed inhibited cell migration, invasion, and proliferation. We further demonstrated that PSPH might promote the invasive capabilities of NSCLC cells through the AKT/AMPK signaling pathway. Conclusion Our results indicate that PSPH may act as a putative oncogene in NSCLC, and may be a vital molecular marker for the metastasis and proliferation of NSCLC cells by regulating the AKT/AMPK signaling pathway.

Epidermal growth factor receptor (EGFR) mutations are associated with leptomeningeal metastases (LM) of nonsmall cell lung cancer and sensitivity to tyrosine kinase inhibitor (TKI) treatment. Owing to the difficulty of obtaining carcinomatous meningeal tissue for analysis, cerebrospinal fluid (CSF) might be an alternative.To investigate the EGFR mutation detection in the CSF of lung adenocarcinoma patients with LM.Twenty-five lung adenocarcinoma patients with LM diagnosed by CSF cytology were retrospectively evaluated. The results of EGFR mutation detection in CSF, the treatment plan, and clinical outcome information were recorded.Nineteen patients had a known EGFR status in their primary tumors. Twenty patients received EGFR mutation analysis in CSF after LM diagnosis and 14 of them with a known EGFR mutation status of both primary tumors and CSF. Ten (71.4%) had the same EGFR gene status. In primary tumors, no T790M mutations were detected, whereas in CSF, 2 L858R cases and 1 19del case had T790M mutations at the same time. The detection rate of T790M mutations in CSF was 18.1% (2 of 11) in all cases with EGFR-sensitive mutations in the primary lesion.EGFR mutation detection in CSF of lung adenocarcinoma patients with LM might be an alternative when leptomeningeal biopsy cannot be applied and may help to guide TKI treatments.

In this work, PANI/Bi12O17Cl2 composites have been successfully synthesized via a simple and green strategy at room temperature. From TEM, EDS-mapping and DRS results, it can be seen that conducting polymers PANI loaded well on the Bi12O17Cl2, and extended the light-absorption region of the composite to a higher wavelength. The photocatalytic activity was evaluated by removal of CIP under visible light (λ > 420 nm). The degradation rate of the optimal ratio composite is about 2 times to that of Bi12O17Cl2. The photodegradation intermediates of CIP were identified by mass spectrometry and the toxicity of the CIP photodegraded products were investigated via a microbiological antibacterial reaction. The results indicated the low-toxicity of the degraded products. Photocurrent results showed that the high separation and transfer of the photogenerated charge carriers were implemented by the introduction of PANI into the surface of Bi12O17Cl2 material. Furthermore, long wavelength light (λ > 550 nm) degradation of CIP indicated that the PANI played as photosentizer could extend the light absorption region and thus enhance the photocatalytic ability. The reaction rate constant of optimal ratio PANI/Bi12O17Cl2 composite was 3.1 times to Bi12O17Cl2. Eventually, a possible photocatalysis mechanism was proposed.

The sensor for thymine detection has a great significance in the analysis of deoxyribonucleic acid in living organisms. In this work, a series of bis-BODIPY derivatives, namely, 3a–3c with diamido bridges were designed and prepared in yields of 74–77% through a simple procedure. The sensing abilities of compounds 3a–3c for adenine, guanine, cytosine, thymine, glucose, urea and haemoglobin were examined by UV-vis and fluorescence spectra. Sample 3b was demonstrated to be a good selective sensor for thymine among all the other tested species. The detection limit of sample 3b was as low as 1.53 × 10−6 M for thymine. The competitive experiments suggested that the selective sensor for thymine was influenced slightly by the other species. The proposed sensing mechanism was confirmed by FT-IR, 1H NMR and MS spectra. Sample 3b exhibited good bioimaging performance with bright green fluorescence in living cell imaging. The significant fluorescence quenching phenomenon after the addition of thymine implied the sensing ability of sample 3b for thymine in living cells.

Phosphor-converted white light-emitting diodes (w-LEDs) have become the new generation of lighting. Several strategies have been introduced to realize a high CRI value for illumination. However, these strategies suffer from new problem(s), such as reabsorption, different deterioration rates among the phosphors, different thermal stability for diverse emission bands, and/or the decrease of quantum efficiency for the phosphor. Therefore, it is desired to develop new phosphors that not only realize a high CRI value for w-LEDs, but also resolve the above problems. In this work, a site-preference driven color-tunable Eu2+-activated K2Ca(PO4)F phosphor was prepared. The color-tunable phosphor exhibits two broad emission bands peaking at 485 and 660 nm upon UV excitation. White emission is realized in K2Ca(PO4)F:0.006Eu2+. The internal and external quantum efficiencies of the white-emitting phosphor are 91.5 and 66.9%, respectively. The phosphor also exhibits good thermal stability, namely, the emission intensity at 423 K maintains >80% of that at room temperature, and the intensity ratio between the two emission bands remains nearly unchanged within 423 K. A white LED device has also been fabricated using a 365 nm LED chip and K2Ca(PO4)F:0.006Eu2+, showing a high color rendering index (Ra = 87.6). These results indicate that the K2Ca(PO4)F:Eu2+ phosphor is a promising candidate for UV-pumped w-LEDs.

Autonomous vehicles rely on sensors to measure road condition and make driving decisions, and their safety relies heavily on the reliability of these sensors. Out of all obstacle detection sensors, ultrasonic sensors have the largest market share and are expected to be increasingly installed on automobiles. Such sensors discover obstacles by emitting ultrasounds and analyzing their reflections. By exploiting the built-in vulnerabilities of sensors, we designed random spoofing, adaptive spoofing, and jamming attacks on ultrasonic sensors, and we managed to trick a vehicle to stop when it should keep moving, and let it fail to stop when it should. We validate our attacks on stand-alone sensors and moving vehicles, including a Tesla Model S with the “Autopilot” system. The results show that the attacks cause blindness and malfunction of not only sensors but also autonomous vehicles, which can lead to collisions. To enhance the security of ultrasonic sensors and autonomous vehicles, we propose two defense strategies, single-sensor-based physical shift authentication that verifies signals on the physical level, and multiple sensor consistency check that employs multiple sensors to verify signals on the system level. Our experiments on real sensors and MATLAB simulation reveal the validity of both schemes.

Quick response (QR) codes have been widely used in mobile applications due to its convenience and the pervasive built-in cameras on smartphones. Recently, however, attacks against QR codes have been reported that attackers can capture a QR code of the victim and replay it to achieve a fraudulent transaction or intercept private information, just before the original QR code is scanned. In this study, we enhance the security of a QR code by identifying its authenticity. We propose SCREENID, which embeds a QR code with information of the screen which displays it, thereby the QR code can reveal whether it is reproduced by an adversary or not. In SCREENID, PWM frequency of screens is exploited as the unique screen fingerprint. To improve the estimation accuracy of PWM frequency, SCREENID incorporates a model for the interaction between the camera and screen in the temporal and spatial domains. Extensive experiments demonstrate that SCREENID can differentiate screens of different models, types, and manufacturers, thus improve the security of QR codes.

Autonomous vehicles increasingly exploit computer-vision-based object detection systems to perceive environments and make critical driving decisions. To increase the quality of images, image stabilizers with inertial sensors are added to alleviate image blurring caused by camera jitters. However, such a trend opens a new attack surface. This paper identifies a system-level vulnerability resulting from the combination of the emerging image stabilizer hardware susceptible to acoustic manipulation and the object detection algorithms subject to adversarial examples. By emitting deliberately designed acoustic signals, an adversary can control the output of an inertial sensor, which triggers unnecessary motion compensation and results in a blurred image, even if the camera is stable. The blurred images can then induce object misclassification affecting safety-critical decision making. We model the feasibility of such acoustic manipulation and design an attack framework that can accomplish three types of attacks, i.e., hiding, creating, and altering objects. Evaluation results demonstrate the effectiveness of our attacks against four academic object detectors (YOLO V3/V4/V5 and Fast R-CNN), and one commercial detector (Apollo). We further introduce the concept of AMpLe attacks, a new class of system-level security vulnerabilities resulting from a combination of adversarial machine learning and physics-based injection of information-carrying signals into hardware.

Human activities are increasingly recognized as having a critical influence on hydrological processes under the warming of the climate, particularly for dam-regulated rivers. To ensure the sustainable management of water resources, it is important to evaluate how dam construction may affect surface runoff. In this study, using Mann–Kendall tests, the double mass curve method, and the Budyko-based elasticity method, the effects of climate change and human activities on annual and seasonal runoff were quantified for the Yellow River basin from 1961–2018, additionally, effects on runoff were assessed after the construction of the Xiaolangdi Dam (XLD, started operation in 2001) on the Yellow River. Both annual and seasonal runoff decreased over time (p &lt, 0.01), due to the combined effects of climate change and human activities. Abrupt changes in annual, flood season, and non-flood season runoff occurred in 1986, 1989, and 1986, respectively. However, no abrupt changes were seen after the construction of the XLD. Human activities accounted for much of the reduction in runoff, approximately 75–72% annually, 81–86% for the flood season, and 86–90% for the non-flood season. Climate change approximately accounted for the remainder: 18–25% (annually), 14–19% (flood season), and 10–14% (non-flood season). The XLD construction mitigated runoff increases induced by heightened precipitation and reduced potential evapotranspiration during the post-dam period, the XLD accounted for approximately 52% of the runoff reduction both annually and in the non-flood season, and accounted for approximately −32% of the runoff increase in the flood season. In conclusion, this study provides a basic understanding of how dam construction contributes to runoff changes in the context of climate change, this information will be beneficial for the sustainable management of water resources in regulated rivers.

Background Our current study aimed to evaluate the effect of an Glechoma hederacea extract (Hitrechol®) in normal rats and gallstone diseased mice to explore its underlying mechanisms. Normal rats and C57BL/6 mice with/without cholesterol gallstone were used in this study. Methods To monitor the effect of Hitrechol® on bile secretion, bile flow rates at 15 min interval until 2 h post-dosing in normal rats treated with vehicle and Hitrechol® were compared using multiple t-test with a p p Results Despite no significant impact on the bile flow rate, Hitrechol® TID treatment dramatically decreased size and amount of gallstone crystals and total cholesterol level (p ), as well as total bile acid (p ) and several types of bile acid (p ) levels in gallstone disease model mice. Hitrechol® TID treatment could significantly decrease the frequencies of hepatocyte necrosis and lipid aggregation notably as well as increase the antioxidant enzyme level (p ) in the liver. Conclusions Our findings for the first time demonstrated the beneficial effect of Hitrechol® against gallstone via its litholytic, liver-protective and antioxidant activities.

Circular RNAs (circRNAs) were originally thought to result from RNA splicing errors. However, it has been shown that circRNAs can regulate cancer onset and progression in various ways. They can regulate cancer cell proliferation, differentiation, invasion, and metastasis. Moreover, they modulate glucose metabolism in cancer cells through different mechanisms such as directly regulating glycolytic enzymes and glucose transporter (GLUT) or indirectly regulating signal transduction pathways. In this review, we elucidate on the role of circRNAs in regulating glucose metabolism in cancer cells, which partly explains the pathogenesis of malignant tumors, and provides new therapeutic targets or new diagnostic and prognostic markers for human cancers.

Chengzhou Lv, Wei Sun, Jiapeng Huang, Yuan Qin, Xiaoyu Ji, Hao Zhang Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Hao Zhang Email haozhang@cmu.edu.cnBackground: Papillary thyroid carcinoma (PTC) is the most prevalent type of thyroid cancer. Herein, we purposed to explore the expression patterns of circRNAs in PTC with the overarching goal of improving early diagnosis rates for individuals with PTC.Methods: We used RNA deep sequencing to determine the expression patterns of circRNAs in PTC. Besides, RT-qPCR was employed to confirm circRNAs. The diagnostic potential of the circRNAs was explored by constructing ROC curves. GO along with KEGG pathway analyses were utilized to elucidate the potential biological roles of differentially expressed circRNAs. Moreover, we predicted cross talks among circRNAs, miRNAs, and mRNAs, followed by establishment of a ceRNA network.Results: Deep sequencing of four PTC pairs and neighboring nontumor tissues identified 16569 circRNAs, of which, 301 were upregulated and 419 were downregulated. The RT-qPCR data demonstrated that the expression of chr5: 38481299– 38530666-, chr2: 159932176– 159945082-, chr10: 179994– 249088+, chr3: 121378716– 121381532+, and chr1: 237423092– 237445522+ was downregulated, while the expression of chr4: 25665378– 25667298+, chr5: 161330883– 161336769-, chr1: 12578718– 12579412-, chr7: 116695750– 116700284+, and chr7: 116699071– 116700284+ was upregulated. The stability test exhibited that circRNAs were more tolerant to temperature, RNase R, and time. On the other hand, ROC curves illustrated that chr4: 25665378– 25667298+, chr1: 12578718– 12579412-, chr7: 116699071– 116700284+, chr7: 116695750– 116700284+, chr5: 161330883– 161336769-, and chr10: 179994– 249088+ were effective as diagnostic indicators. However, a logistic regression model combining the six indicators achieved a better combined prediction index, with 97.7% sensitivity and 95.3% specificity. Moreover, GO along with KEGG pathway analyses illustrated that differentially expressed circRNAs were linked to tumorigenesis. Furthermore, bioinformatics analyses established a promising ceRNAs network among mRNAs, circRNAs, and miRNAs.Conclusion: Herein, we demonstrated that several circRNAs are promising PTC diagnostic biomarkers. Further study on the functions and mechanisms of these circRNAs may contribute to the understanding of PTC.Keywords: papillary thyroid carcinoma, circular RNA, RNA sequencing, diagnosis, biomarker

Cervical cancer (CC) is one of the most common types of malignant female cancer, and its incidence and mortality are not optimistic. Protein panels can be a powerful prognostic factor for many types of cancer. The purpose of our study was to investigate a proteomic panel to predict the survival of patients with common CC.The protein expression and clinicopathological data of CC were downloaded from The Cancer Proteome Atlas and The Cancer Genome Atlas database, respectively. We selected the prognosis-related proteins (PRPs) by univariate Cox regression analysis and found that the results of functional enrichment analysis were mainly related to apoptosis. We used Kaplan-Meier analysis and multivariable Cox regression analysis further to screen PRPs to establish a prognostic model, including BCL2, SMAD3, and 4EBP1-pT70. The signature was verified to be independent predictors of OS by Cox regression analysis and the area under curves. Nomogram and subgroup classification were established based on the signature to verify its clinical application. Furthermore, we looked for the co-expressed proteins of three-protein panel as potential prognostic proteins.A proteomic signature independently predicted OS of CC patients, and the predictive ability was better than the clinicopathological characteristics. This signature can help improve prediction for clinical outcome and provides new targets for CC treatment.

Metastasis is the major reason for the high mortality of colorectal cancer (CRC) patients and its molecular mechanism remains unclear. Here, we report a novel role of Homeobox A13 (HOXA13), a member of the Homeobox (HOX) family, in promoting CRC metastasis. The elevated expression of HOXA13 was positively correlated with distant metastasis, higher AJCC stage, and poor prognosis in two independent CRC cohorts. Overexpression of HOXA13 promoted CRC metastasis whereas downregulation of HOXA13 suppressed CRC metastasis. Mechanistically, HOXA13 facilitated CRC metastasis by transactivating ATP-citrate lyase (ACLY) and insulin-like growth factor 1 receptor (IGF1R). Knockdown of ACLY and IGFIR inhibited HOXA13-medicated CRC metastasis, whereas ectopic overexpression of ACLY and IGFIR rescued the decreased CRC metastasis induced by HOXA13 knockdown. Furthermore, Insulin-like growth factor 1 (IGF1), the ligand of IGF1R, upregulated HOXA13 expression through the PI3K/AKT/HIF1α pathway. Knockdown of HOXA13 decreased IGF1-mediated CRC metastasis. In addition, the combined treatment of ACLY inhibitor ETC-1002 and IGF1R inhibitor Linsitinib dramatically suppressed HOXA13-mediated CRC metastasis. In conclusion, HOXA13 is a prognostic biomarker in CRC patients. Targeting the IGF1-HOXA13-IGF1R positive feedback loop may provide a potential therapeutic strategy for the treatment of HOXA13-driven CRC metastasis.

Young football players are hypothesized to experience damage to the brain and brain function from repeated subconcussive head acceleration events (HAEs) during practices and games. Such damage may cause delayed cognitive and mental problems. Resting state fMRI (rs-fMRI) is an effective non-invasive method to detect alterations in brain functional connectivity. Seed-based rsfMRI analysis using the central node of the default mode network (DMN) as the seed is a common approach to measuring intrinsic changes of the DMN, accepted as a key network in brain function. Seed-based rs-fMRI analysis of the DMN was used to explore how age, HAE intensity, and HAE counts influence brain connectivity in youth athletes (ages 12-18). Middle school and high school football players and peer controls were studied using rs-fMRI before and after one season of competition. An identifiability matrix was generated from the seed-based connectivity matrix, allowing measurement of similarity between pre-season and post-season functional connectivity. The consistency of seed-based brain functional connectivity we observed across the season of play for players has no statistically significant difference from controls. The identifiability matrix exhibited no relation to the number and magnitude of any subset of HAEs experienced which rejected our hypothesis. Another finding is that high school football players exhibited the largest percentage increase in identification from middle school football players in the somatomotor network over other resting-state networks.

With the rapid growth of online services, the number of online accounts proliferates. The security of a single user account no longer depends merely on its own service provider but also the accounts on other service platforms(We refer to this online account environment as Online Account Ecosystem). In this paper, we first uncover the vulnerability of Online Account Ecosystem, which stems from the defective multi-factor authentication (MFA), specifically the ones with SMS-based verification, and dependencies among accounts on different platforms. We propose Chain Reaction Attack that exploits the weakest point in Online Account Ecosystem and can ultimately compromise the most secure platform. Furthermore, we design and implement ActFort, a systematic approach to detect the vulnerability of Online Account Ecosystem by analyzing the authentication credential factors and sensitive personal information as well as evaluating the dependency relationships among online accounts. We evaluate our system on hundreds of representative online services listed in Alexa in diversified fields. Based on the analysis from ActFort, we provide several pragmatic insights into the current Online Account Ecosystem and propose several feasible countermeasures including the online account exposed information protection mechanism and the built-in authentication to fortify the security of Online Account Ecosystem., Comment: 11 pages, 11 figures