Interventional hepatic arterial infusion chemotherapy of infusional fluorouracil, leucovorin, and oxaliplatin (HAIC-FO) displayed an encouraging safety profile and antitumor activity in a previous ...phase II trial and a propensity-score-matching study involving patients with locally advanced hepatocellular carcinoma (HCC).
In this open-label, phase III trial, patients with advanced HCC, previously untreated with systemic therapy, were randomly assigned in a 1:1 ratio to receive HAIC-FO or sorafenib. The primary end point was overall survival (OS) in the intention-to-treat population. An exploratory model for predicting the efficacy of HAIC-FO on the basis of genomic sequencing was developed.
Between May 2017 and May 2020, 262 patients were randomly assigned. The median tumor size was 11.2 cm (interquartile range, 8.5-13.7 cm). Macrovascular invasion was present in 65.6%, and the percentage of patients with > 50% tumor volume involvement of the liver and/or Vp-4 portal vein tumor thrombosis was 49.2%. At data cutoff (October 31, 2020), median OS was 13.9 months for HAIC-FO and 8.2 for sorafenib (hazard ratio HR 0.408; 95% CI, 0.301 to 0.552;
< .001). Tumor downstaging occurred in 16 (12.3% of 130) patients receiving HAIC-FO, including 15 receiving curative surgery or ablation, and finally achieving a median OS of 20.8 months, with a 1-year OS rate of 93.8%. In high-risk subpopulations, OS was significantly longer with HAIC-FO than with sorafenib (10.8 months
5.7 months; HR 0.343; 95% CI, 0.219 to 0.538;
< .001). A newly developed 15-mutant-gene prediction model identified 83% of patients with response to HAIC-FO. HAIC-FO responders had longer OS than HAIC-FO nonresponders (19.3 months
10.6 months; HR 0.323; 95% CI, 0.186 to 0.560;
= .002).
HAIC-FO achieved better survival outcomes than sorafenib in advanced HCC, even in association with a high intrahepatic disease burden.
Sorafenib is the first-line medication for advanced hepatocellular carcinoma (HCC), but it can only extend limited survival. It is imperative to find a combination strategy to increase sorafenib ...efficacy. Artesunate is such a preferred candidate, because artesunate is clinically well-tolerated and more importantly both drugs can induce ferroptosis through different mechanisms. In this study we investigated the combined effect of sorafenib and artesunate in inducing ferroptosis of HCC and elucidated the involved molecular mechanisms. We showed that artesunate greatly enhanced the anticancer effects of low dose of sorafenib against Huh7, SNU-449, and SNU-182 HCC cell lines in vitro and against Huh7 cell xenograft model in Balb/c nude mice. The combination index method confirmed that the combined effect of sorafenib and artesunate was synergistic. Compared with the treatment with artesunate or sorafenib alone, combined treatment induced significantly exacerbated lipid peroxidation and ferroptosis, which was blocked by N-acetyl cysteine and ferroptosis inhibitors liproxstatin-1 and deferoxamine mesylate, but not by inhibitors of other types of cell death (z-VAD, necrostatin-1 and belnacasan). In Huh7 cells, we demonstrated that the combined treatment induced oxidative stress and lysosome-mediated ferritinophagy, two essential aspects of ferroptosis. Sorafenib at low dose mainly caused oxidative stress through mitochondrial impairments and SLC7A11-invovled glutathione depletion. Artesunate-induced lysosome activation synergized with sorafenib-mediated pro-oxidative effects by promoting sequential reactions including lysosomal cathepsin B/L activation, ferritin degradation, lipid peroxidation, and consequent ferroptosis. Taken together, artesunate could be repurposed to sensitize sorafenib in HCC treatment. The combined treatment can be easily translated into clinical applications.
A multiple-input-multiple-output dielectric resonator antenna with enhanced isolation is proposed in this letter for the future 5G millimeter (mm)-wave applications. Two rectangular dielectric ...resonators (DRs) are mounted on a substrate excited by rectangular microstrip-fed slots underneath DRs. Each DR has a metal strip printed on its upper surface moving the strongest part of the coupling field away from the exciting slot to improve the isolation between two antenna elements. The proposed antenna obtains a simulated impedance bandwidth (S11 ≤ -10 dB) from 27.25 to 28.59 GHz, which covers the 28 GHz band (27.5-28.35 GHz) allocated by the Federal Communications Commission for the 5G applications. A maximum improvement of 12 dB on the isolation over 27.5-28.35 GHz is achieved. The mechanism of the isolation improvement and the design procedure are given in this letter. A prototype is manufactured and measured as a validation of the proposed decoupling method.
Vehicular content centric networks (VCCNs) emerge as a strong candidate to be deployed in information-rich applications of vehicular communications. Due to vehicles' mobility, it becomes rather ...inefficient to establish end-to-end connections in VCCNs. Consequently, content packets are usually sent back to the requesting node via different paths in VCCNs. To improve network performance of VCCNs, node mobility should be exploited for vehicles to serve as relays and to carry data for delivery. In this paper, we propose a scheme called cooperative caching based on mobility prediction (CCMP) for VCCNs. The main idea of CCMP is to cache popular contents at a set of mobile nodes that may visit the same hot spot areas repeatedly. In our CCMP scheme, we use prediction based on partial matching to predict mobile nodes' probability of reaching different hot spot regions based on their past trajectories. Vehicles with longer sojourn time in a hot region can provide more services and should be preferred as caching nodes. To solve the problem of limited buffer at each node, we design a cache replacement based on content popularity to guarantee that only popular contents are cached. We evaluate CCMP through the opportunistic network environment simulator for its salient features in success ratio and content access delay compared to other state-of-the-art schemes.
Lipophilic biphenylthiophene‐ and phenanthrothiophene‐triazine compounds, BPTTn and CPTTn, respectively, were prepared by a tandem procedure involving successive Suzuki‐Miyaura coupling and Scholl ...cyclodehydrogenation reactions. These compounds display photoluminescence in solution and in thin film state, solvatochromism with increasing solvent's polarity, as well as acidochromism and metal ion recognition stimuli‐responsive fluorescence. Protonation of BPTT10 and CPTT10 by trifluoroacetic acid results in fluorescence quenching, which is reversibly restored once treated with triethylamine (ON‐OFF switch). DFT computational studies show that intramolecular charge transfer (ICT) phenomena occurs for both molecules, and reveal that protonation enhances the electron‐withdrawing ability of the triazine core and reduces the band gap. This acidochromic behavior was applied to a prototype fluorescent anti‐counterfeiting device. They also specifically recognize Fe3+ through coordination, and the recognition mechanism is closely related to the photoinduced electron transfer between Fe3+ and BPTT10/CPTT10. CPTTn self‐assemble into columnar rectangular (Colrec) mesophase, which can be modulated by oleic acid via the formation of a hydrogen‐bonded supramolecular liquid crystal hexagonal Colhex mesophase. Finally, CPTTn also form organic gels in alkanes at low critical gel concentration (3.0 mg/mL). Therefore, these star‐shaped triazine molecules possess many interesting features and thus hold great promises for information processing, liquid crystal semiconductors and organogelators.
Triazine‐based mesogens with three pending discoid arms have been shown to self‐organize into rectangular columnar mesophases and form gels in various solvents. The solvatochromic‐, acidochromic‐ and metal recognition‐response photoluminescence of these mesogens offer applications in stimuli‐responsive fluorescence anti‐counterfeiting and as selective metal‐ion recognition.
ABT-737 is a small-molecule antagonist of BCL-2 currently under evaluation in clinical trials in the oral form of ABT-263. We anticipate that acquired resistance to this promising drug will ...inevitably arise. To study potential mechanisms of resistance to ABT-737, we derived resistant lines from initially sensitive OCI-Ly1 and SU-DHL-4 lymphoma cell lines via long-term exposure. Resistance was based in the mitochondria and not due to an inability of the drug to bind BCL-2. Resistant cells had increased levels of BFL-1 and/or MCL-1 proteins, which are not targeted by ABT-737. Proapoptotic BIM was displaced from BCL-2 by ABT-737 in both parental and resistant cells, but in resistant cells, BIM was sequestered by the additional BFL-1 and/or MCL-1. Decreasing MCL-1 levels with flavopiridol, PHA 767491, or shRNA restored sensitivity to ABT-737 resistant cells. MCL-1 was up-regulated not by protein stabilization but rather by increased transcript levels. Surprisingly, in addition to stable increases in MCL-1 transcript and protein in resistant cells, there was a dynamic increase within hours after ABT-737 treatment. BFL-1 protein and transcript levels in resistant cells were similarly dynamically up-regulated. This dynamic increase suggests a novel mechanism whereby modulation of antiapoptotic protein function communicates with nuclear transcriptional machinery.
Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer with poor prognosis. This study designated to figure out the effects of Ubiquitin Specific Peptidase 36 (USP36) on NSCLC. ...Data of this study demonstrated that upregulation of USP36 was observed in NSCLC tissues and cell lines. Overexpression of USP36 promoted NSCLC cell proliferation and inhibited NSCLC cell apoptosis. Knockdown of USP36 decreased Ketohexokinase A (KHK-A) and increased KHK-C expression at both RNA and protein levels. Expression of c-MYC and hnRNPH1/H2 was positively correlated with the expression of USP36. Upregulation of c-MYC reversed the downregulation of hnRNPH1/H2 induced inhibition of USP36. Overexpression of hnRNPH1/H2 reversed the downregulation of KHK-A induced inhibition of USP36. Results of in vivo xenograft model were consistent with the findings of in vitro experiments. In summary, overexpression of USP36 in NSCLC accelerated tumor growth through upregulation of KHK-A, which was medicated by stabilizing c-MYC to increase hnRNPH1/H2 expression.
•Thermally activated persulfate (TAP) technology can decompose CBZ efficiently.•Sulfate radicals play the primary role in TAP oxidation.•The best CBZ degradation can be achieved at acidic ...conditions.•Coexisting anions and cations exhibit opposite effect on the CBZ degradation.•Six intermediate products are identified using LC–MS/MS.
Sulfate radicals-based advanced oxidation processes have been applied in water treatment and in situ chemical oxidation. Batch experiments were conducted to investigate the influencing factors including persulfate dosage, initial carbamazepine (CBZ) concentrations, solution pH, coexisting inorganic anions and cations on the decomposition of CBZ using thermally activated persulfate (TAP) technology. The results showed that TAP oxidation was efficient process for the CBZ degradation in water. The generation of sulfate radicals was accounted for the CBZ degradation in TAP system. The CBZ degradation rate constant increased as persulfate dosage increased and decreased as the initial CBZ concentrations increased. The CBZ decomposition rate decreased with the increasing pH and the best degradation occurred at pH 3. The exception was the strong alkaline condition under which a higher CBZ degradation performance was achieved. Coexisting inorganic anions slowed down the CBZ degradation to different degrees and the inhibiting effect abided by the following order: CO32->HCO3->Cl->SO42->NO3-. In contrast, coexisting cations could significantly enhance the CBZ degradation, and the promoting effect was in the order of Fe2+>Cu2+>Fe3+. In this study, six major intermediate products were generated during the TAP oxidation.
Ten‐element MIMO antenna for 5G terminals Deng, Jing‐Ya; Yao, Jiao; Sun, Dong‐Quan ...
Microwave and optical technology letters,
December 2018, 2018-12-00, 20181201, Letnik:
60, Številka:
12
Journal Article
Recenzirano
A MIMO antenna with 10 elements operating on 3.3‐3.6 GHz for 5G applications is proposed. The 10 elements of the proposed MIMO antenna include six monopoles and four slots with coupled feed. The ...monopoles and slots are alternately placed along the four sides of the mobile terminal with different radiating modes. The antenna is printed on a planar substrate, resulting in low cost and easy fabrication. The antenna is simulated, fabricated, and measured, the isolations are better than 11 dB, the efficiencies are about 50‐76%. The envelop correlation coefficient (ECC) is lower than 0.15 between any two antenna elements, and the calculated channel capacity is reached about 48‐51 bps/Hz, which is 7 bps/Hz lower than the ideal 10 × 10 MIMO channel.
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•The preparation of biomaterial-based encapsulated probiotics (BEP) is summarized.•The BEP in diversified biomedical applications are highlighted.•The challenges and perspectives for ...the BEP are proposed.
Probiotics have recently received increasing attention in a range of biomedical applications, such as antimicrobial agents, tissue repair and regeneration, as well as disease treatment. However, the activity and viability of probiotics are significantly affected by complicated tissue/organ environment and thus the probiotics can not stay steady at the target location. Probiotic encapsulation is developed as a biotechnological tool to cope with the technological issues derived from the handling and application of probiotics. Encapsulating living probiotics within appropriate biomaterials is a crucial extension of the functions of probiotics and further development. Biomaterials-based probiotic encapsulation not only protects the vitality of the probiotics but also is a better way to make them delivered to their target location. This review summarizes recent advances of biomaterial-based encapsulated probiotics, including encapsulation methods, encapsulation materials, and encapsulation effects. Further, we highlight biomaterial-based encapsulated probiotics in diversified biomedical applications, including the gastrointestinal tract, oral cavity, vagina, and skin. In the final section, current challenges faced by biomaterial-based encapsulated probiotics are outlined and future perspectives for advancing this research are proposed.
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