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Cholangiocarcinoma is a highly aggressive malignant tumor disease with the increasing incidence and mortality. It’s urgent to identify specific biomarkers for cholangiocarcinoma treatment and diagnosis. Recent studies have noted the importance of lncRNAs in cancer and the following downstream mechanism with miRNAs network has been a hotspot. This work aimed to discover the role of lncRNA HCG18 and its possible downstream mechanism in cholangiocarcinoma tumor progression. Initially, through bioinformatics tools, we observed abnormal expression of lncRNA HCG18 in cholangiocarcinoma. In vitro experiments like (CCK-8, EdU, colony formation, flow cytometry, transwell, wound healing assays) and animal study confirmed that lncRNA HCG18 served as a cancer-promoting gene, promoted cancer proliferation, migration and invasion abilities. Besides, we found cancer cell-secreted exosomes transitted HCG18 to surrounding tumor cells and accelerated tumor growth and metastasis. After that, we confirmed HCG18 directly interacted with miR-424-5p through FISH, RIP and dual luciferase reporter assays with negative modulation. The inhibition of miR-424-5p reversed the HCG18 knockdown induced suppression on cholangiocarcinoma cancer cells. More specific, miR-424-5p targeted to SOX9 contributed to cholangiocarcinoma growth and metastasis through mediating PI3K/AKT pathway. In conclusion, these findings provide solid evidence of lncRNAs/miRNAs regulation in cholangiocarcinoma progression.

With two groups of numerical experiments with and without the cold-core eddy (CCE), the impacts of the CCE on the upper-ocean responses to Typhoon Trami (2018) were investigated using a coupled atmosphere–ocean model. It is commonly accepted that the CCE promotes the sea surface cooling (SSC) primally through the enhanced vertical mixing, while the contributions from the wind-driven advection and the near-inertial advection to the differences in the sea surface temperature (dSST) were underestimated. This study found that the presence of CCE contributed to the stronger along-track cold advection, which dominated the increase in the SSC near the radius of maximum wind (RMW) to the right of Trami’s track, and the stronger cross-track warm advection was acting to prevent the cooling induced by the vertical mixing. During the relaxation stage, the stronger near-inertial advection within the CCE accounted largely for the amplification and the redistribution of the dSST. As for the dynamic responses, the enhanced upwelling and downwelling within the CCE explained the larger cooling and warming in the subsurface temperature oscillations. The wind-driven acceleration of the currents in the mixing layer was larger during the typhoon–eddy interaction so that the CCE became an efficient mixer, thus contributing to the rapid surfacing of the cold water and the ensuing stronger wind-driven advection. These results highlight the importance of the advection processes in the modulating effect of the CCE. Therefore, 3D ocean models are needed to incorporate the mesoscale features of the oceanic eddies for realistically reproducing the upper-ocean responses to tropical cyclones (TCs).

Background Cholangiocarcinoma (CHOL) is the second most common primary hepatic malignant tumor, following hepatocellular carcinoma (HCC). CHOL is highly aggressive and heterogeneous resulting in poor prognosis. The diagnosis and prognosis of CHOL has not improved in the past decade. Acyl-CoA synthetase long-chain family member 4 (ACSL4) is reported to be associated with tumors, however, its role in CHOL has not been revealed. This study is mainly for exploring the prognostic values and potential function of ACSL4 in CHOL. Methods We investigated the expression level and prognostic value of ACSL4 in CHOL based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. TIMER2.0, TISIDB and CIBERSORT databases were utilized to assess the associations between ACSL4 and immune infiltration cells in CHOL. Single-cell sequencing data from GSE138709 was analyzed to study the expression of ACSL4 in different types of cells. ACSL4 co-expressed genes were analyzed by Linkedomics. Additionally, Western Blot, qPCR, EdU assay, CCK8 assay, transwell assay and wound healing assay were performed to further confirm the roles of ACSL4 in the pathogenesis of CHOL. Results We found that the level of ACSL4 was higher in CHOL and it was correlated with the diagnosis and prognosis of CHOL patients. Then, we observed that the infiltration level of immune cells was related to the level of ACSL4 in CHOL. Moreover, ACSL4 and its co-expressed genes were mainly enriched in metabolism-related pathway and ACSL4 is also a key pro-ferroptosis gene in CHOL. Finally, knockdown of ACSL4 could reverse the tumor-promoting effect of ACSL4 in CHOL. Conclusions The current findings demonstrated ACSL4 may as a novel biomarker for CHOL patients, which might regulate immune microenvironment and metabolism resulting in poor prognosis.

Purpose: To evaluate the efficacy and safety of lenvatinib in combination with transarterial chemoembolization (TACE) as an adjuvant therapy in HCC patients with high-risk of postoperative recurrence. Methods: This study was a prospective cohort study. Patients who met the eligible criteria were recruited between November 2018 to May 2021 from 8 hepatobiliary centers in China. The primary endpoint was disease-free survival (DFS). The secondary endpoints were overall survival (OS) and safety. The treatment-related adverse events (AEs) were recorded throughout the entire study period. Results: A total of 297 patients were enrolled, with 147 patients in the TACE + Lenvatinib (Len) group and 150 patients in the TACE group. The baseline characteristics were well balanced between the two groups. Patients in the TACE + Len group achieved significantly better DFS. The median DFS was 19.0 months [95% confidence interval (CI), 14.0-25.0] and 10.0 months [95% CI, 8.0-13.0] in the TACE + Len and TACE group, respectively (log-rank test p= 0.011). The adjusted hazard ratio (HR) of disease recurrence for baseline prognostic variables between the two groups was 0.68 (95% CI, 0.50–0.91, p = 0.009). Lenvatinib treatment-related AEs of grade 3 or 4 occurred in 28.6% of the patients in TACE + Len group. Conclusions: This study suggested that adjuvantTACE plus lenvatinib a promising approach for HCC patients with high-risk of postoperative recurrence, which could significantly reduce postoperative recurrence and prolong survival with a manageable safety profile.

Background: Hepatocellular carcinoma (HCC) is a common malignant tumor worldwide with a poor prognosis. Amounting studies revealed that long non-coding RNAs (lncRNAs) show important roles in various biological processes. The purpose of this study was to explore the biological function and potential molecular mechanism of CASC7 in HCC. Methods: CASC7 expression in HCC cell lines was detected by qRT-PCR. The expressions of CASC7 and miR-340-5p were changed by transfection of miR-340-5p mimic, the CASC7 overexpression and knockdown plasmids. The interaction between CASC7 and miR-340-5p was assessed by a Dual-Luciferase reporter assay. The biological functions of CASC7 were evaluated by CCK-8, colony formation assay, ROS assay kit, immunofluorescence and flow cytometry (FCM). Results: CASC7 was upregulated in HCC cell lines. CASC7 overexpression significantly promoted cell proliferation, as well as inhibited apoptosis and oxidative stress. In contrast, CASC7 knockdown could reverse these above changes. The result of the Dual-luciferase reporter assay revealed that CASC7 directly targeted miR-340-5p and negatively regulated its expression. In addition, CASC7 promoted proliferation and inhibited apoptosis of HCC cells through activating Nrf2 pathway by downregulating miR-340-5p. Conclusions: In summary, CASC7 promotes HCC tumorigenesis and progression through the Nrf2 pathway by targeting miR-340-5p, which may provide a new target for therapy of HCC.

Electromagnetic wave (EMW) absorbing materials have excellent potential for various applications in civil engineering and the military. In this study, siliconboron carbonitride (SiBCN) ceramics with excellent EMW absorption capability and oxidation resistance were obtained by adjusting the boron content. The results revealed that the graphite crystallite size in the SiBCN ceramics increased from 3.42 to 3.78 nm, whereas the thickness of the oxide layer decreased from 16.6 to 8.2 μm. The highest electrical conductivity and permittivity for the SiBCN ceramics were obtained when the boron content was 5%. The minimum reflection loss was −35.25 dB at 10.57 GHz and a ceramic thickness of 2.0 mm. At a temperature of 600 °C, the SiBCN ceramic exhibited excellent EMW attenuation ability; particularly, the minimum reflection loss reached −29.18 dB at 9.65 GHz and a ceramic thickness of 2.5 mm. The superior EMW absorption properties of the SiBCN ceramics at high temperatures can be ascribed to the synergistic effect of relaxation and conductivity. The results suggest that boron could enhance the transformation of amorphous carbon into crystalline graphite and increase the number of heterointerfaces and conductive paths. This work provides a method for obtaining SiBCN ceramics with excellent EMW absorption properties.

Purpose: Previous reports have shown that IL-1α–MyD88–IL-6 signaling is essential in promoting hepatocellular carcinoma (HCC) development in a diethylnitrosamine (DEN)-induced mouse model. We aimed to determine whether interleukin (IL)-1α regulates HCC development in humans.Methods: HBV-associated HCC tissue, corresponding adjacent tissue, and normal tissue samples were obtained from 80 male and 36 female patients. IL-1α, ERα, IL-6, and MyD88 were quantified by using real-time PCR and Western blot. Stem-loop PCR was used to quantify miR-22 expression. Luciferase reporter assays were used to study transcriptional regulation.Results: IL-1α was highly expressed in male tumor adjacent tissue compared with normal tissue (P = 0.025); however, this was not the case for female subjects. A linear relationship was observed between increased IL-1α and decreased ERα expression in male tumor adjacent tissue (r = −0.616, P = 0.004). Our results also indicated that estrogen (E2) was suppressed upon IL-1α secretion in ERα-overexpressed HCC cells. We detected high expression of miR-22 in male tumor adjacent tissue compared with controls (P = 0.027); furthermore, we showed that miR-22 downregulates ERα transcription by targeting the 3′-untranslated region. In the DEN-induced model, IL-1α was highly expressed in sprouting tumors and gradually decreased in conjunction with HCC development.Conclusion: Overexpression of miR-22 in male tumor adjacent tissue was associated with downregulated ERα expression, potentially by attenuating the protective effect of estrogen and causing increased IL-1α expression. These results may explain the high incidence of HBV-associated HCC in the male population. Clin Cancer Res; 17(17); 5593–603. ©2011 AACR.

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The cold wake caused by a tropical cyclone (TC) extends for hundreds of kilometers and persists for several weeks, thus influencing the surface response for any subsequent TCs that might pass over it. It is commonly accepted that sea-surface temperature (SST) cooling, as produced by a single TC, occurs primarily through vertical mixing. However, when there are sequential TCs, the earlier TC can dramatically change the thermal structure of the upper ocean, which may influence the subsequent development of a latter-occurring TC (LTC). Therefore, the contribution of horizontal advection and vertical mixing to SST-cooling during the passage of LTCs is of great interest. Using a 19-year-long observational dataset and the heat budget analysis of an idealized numerical simulation, the SST change during the passage of sequential TCs is investigated. The results demonstrate that, on average, the SST cooling caused by the LTC shows an overall decreasing trend with enhanced lingering wakes. Budget analysis of the model simulations suggests that an earlier TC can suppress the vertical mixing induced by an LTC mainly through an alteration of dynamics within the deepened mixed layer and that the contribution of vertical mixing to the SST cooling is weaker due to the intensification of the earlier TC. The weakened vertical mixing dominates the decreased SST cooling induced by an LTC. In contrast, the cold wake generated by an earlier TC can produce more cold water on the right side of the TC’s track, which contributes to stronger horizontal advection upon the arrival of the LTC. In general, the effects of the earlier TC can suppress the sea-surface thermal response to an LTC. If the contribution of the horizontal advection to SST cooling is neglected, the SST cooling induced by an LTC could be reduced by about 40%. As for the response of the sub-surface water to the passage of an LTC, the weakened warm anomaly induced by vertical mixing and the enhanced cooling anomaly caused by the vertical advection explain the reduced tendency for the mixed layer to deepen. As a result, the tendency for the mixed layer depth (MLD) to increase is suppressed during the passage of an LTC. These results highlight the importance of optimally depicting cold wakes in numerical simulations to improve the prediction of the upper ocean’s response to sequential TCs.

Polymer-derived SiBCN ceramics (PDCs-SiBCN) are promising ultrahigh-temperature ceramics owing to their excellent high-temperature oxidation resistance and electromagnetic wave (EMW)-absorbing capa...

The sphere decoding (SD) algorithm can provide (sub)optimal solutions with reduced computational complexity of maximum likelihood (ML) detection for multi-input multi-output (MIMO) communication systems. In this paper, we propose a novel low complexity symmetric-coded based SD algorithm for short polar codes with low rate. At the encoding stage, the first N/2 sub-channels transmit the frozen bits, while the information bits are selected from the latter N/2 sub-channels. Two symmetric codes are generated due to the mathematical structure of the generator matrix, which is well conditioned to the SD search. At the decoding stage, the presented SD algorithm computes the Euclidean distance value by the combined signals to estimate the latter N/2 input bits. Furthermore, the backtrack operation starts from the earlier $$(N/2+1)$$ ( N / 2 + 1 ) -th bit, which can significantly reduce the average visited nodes (AVN). Simulation results show that, compared to the original SD algorithm, the presented variant of the SD algorithm can reduce the AVN to $$0.9\%$$ 0.9 % for the polar code P(64, 14) at SNR = 1 dB with a performance loss within 0.2 dB. The presented SD algorithm may find applications in MIMO systems where the complexity of the standar ML detection increases exponentially with the transmitting antennas.

In order to reduce the sintering temperature and improve the mechanical properties of B

In order to improve the mechanical properties of B4C ceramics, B4C@TiB2 composite powders with core-shell structure are prepared by molten salt method using B4C and Ti powders as raw materials. And B4C ceramics were prepared from B4C@TiB2 composite powders by spark plasma sintering (SPS). The results show that the B4C@TiB2 composite powders exhibit intact core-shell structure. The B4C@TiB2 composite powders improves the mass transfer during spark plasma sintering. When the molar ratio of B4C/Ti is 2/1, the relative density, Vickers hardness, fracture toughness and flexural strength of the BT1/2 sample are 94.2%, 26.9 GPa, 5.34 MPa·m1/2 and 570 MPa, respectively, which is best comprehensive properties.

The effect of B4C addition (0, 3 wt%, 6 wt%, 9 wt%) on the mechanical properties and oxidation resistance of Al2O3-C refractory ceramics was studies in the paper. The results indicated that the addition of B4C could reduce the apparent porosity, increase the mechanical strengths and improve the oxidation resistance. After fired at 1100 °C, the specimen with 6 wt% B4C achieved lowest porosity and permanent linear change. The cold crushing strength was improved from 14.65 MPa to 47.18 MPa. The cold modulus of rupture was significantly improved from 12.1 MPa to 36.29 MPa. When the fired temperature rose to 1450 °C, the lowest porosity and permanent linear change were obtained when B4C additive was 3 wt%. CCS was significantly improved from 12.40 MPa to 57.32 MPa. CMOR was also increased from 7.16 MPa to 28.71 MPa correspondingly. Meanwhile, the oxidation index could be also reduced from 47.6% to 3.9% when B4C content was 6 wt%. These improved properties were due to the formation of liquid phase B2O3 by the reaction between B4C and O2/CO. The compact structure was constructed by volumetric expansion of B2O3.

B4C, Si, Al, and γ-Al2O3 were used as raw materials, formed β-Sialon and SiC in situ by solid-state reaction for preparation of B4C composite powder. β-Sialon and SiC grains are uniformly and dispersedly distributed in the composite powder. The effects of the molar ratio of raw materials, nitridation temperature and soaking time for the phase composition, and microstructure of the composite powder were studied. When the molar ratio of B4C and Si is 2: 3, the composite powder with columnar β-Sialon grains growing alternately can be prepared after nitridation at 1500°C for 4 h. The liquid phase formed by the melting of Si at high temperature promoted the dissolution of B4C and the formation of SiC. When the nitridation temperature was increased or the soaking time was prolonged, the gas phase volatilization of Si and Al was intensified, SiC and AlN whiskers tend to be formed in the composite powder.

Si

In this study, a novel phosphate-based adhesive was prepared by using homemade aluminum phosphate as a matrix and by adding different fillers simultaneously. The effects of calcination temperature and filler composition on the bonding mechanism and high-temperature bonding strength of the adhesive for high-temperature alloys were studied. The results indicated that the crystalline transformation of AlPO4 occurred at 500 °C. AlPO4 has two crystalline forms at 500 °C: orthorhombic and hexagonal. The addition of CuO to the fillers resulted in the exchange of Fe and Cu at the substrate interface and enhanced the high-temperature bonding strength of the specimens. The maximum tensile strength of the specimens reached 3.9 MPa at 500 °C. These composites have potential applications in aviation, aerospace, and other fields.

Background: Pemigatinib is a selective FGFR inhibitor that showed effectiveness and tolerability in patients with cholangiocarcinoma (CAA) with FGFR2 fusion or rearrangement. Data from prior data cutoffs (primary: Jan 29th, 2021; initial update: Dec 20th, 2021) showed that patients receiving pemigatinib had durable responses. Confirmed objective response rate (ORR) (60%) met the primary endpoint, median duration of response (DOR) was 8.3 months, median progression-free survival (PFS) was 9.1 months at the initial update (G-M. Shi et al. ASCO 2022). Safety results were also consistent with previously reported data on pemigatinib. Here we report updated overall survival (OS) results. Methods: Patients aged 18 years or older with recurrent or metastatic CCA that failed at least one prior systemic therapy were enrolled. Thirty-one subjects with documented FGFR2 fusion or rearrangement received 13.5 mg pemigatinib. The primary efficacy endpoint was ORR assessed by the independent radiological review committee (IRRC) per RECIST V1.1. And the second endpoints included disease control rate (DCR), DOR, PFS, and OS. Updated OS were evaluated by Cox proportional hazards model and summarized using Kaplan-Meier methods. Results: At data cutoff (December 28th, 2022), a total of 30 patients were assessed (1 participant excluded due to inadequate FGFR2 aberrant frequency). Median age was 56 years (range, 28-68).With a median OS follow-up of 25.6 months (95% CI, 23.0-25.8), the median OS was 23.9 months (95% CI, 15.2-NC), with 16 (53.3%) OS events. Estimated OS rate at 12 month, 18 month and 24 month were 73.3% (95% CI, 53.7%-85.7%), 66.5% (95% CI, 46.7%-80.4%), and 41.4% (95% CI, 22.4%-59.4%), respectively. No new safety signals were observed. Conclusions: These updated results demonstrated encouraging and durable survival benefit of pemigatinib in Chinese patients with recurrent or metastatic cholangiocarcinoma with FGFR2 fusion or rearrangement. Clinical trial identification: NCT04256980. Editorial acknowledgment: Guoming Shi and Xiaoyong Huang contributed equally to this work. Jian Zhou is the corresponding author. Citation Format: Guoming Shi, Xiaoyong Huang, Tianfu Wen, Tianqiang Song, Ming Kuang, Haibo Mou, Lequn Bao, Haitao Zhao, Hong Zhao, Xielin Feng, Bixiang Zhang, Tao Peng, Yubao Zhang, Xiangcheng Li, Hongsheng Yu, Yu Cao, Yang Luo, Ye Chen, Mingxia Chen, Jia Fan, Jian Zhou. Pemigatinib in Chinese patients with advanced/metastatic or surgically unresectable cholangiocarcinoma Including FGFR2 fusion or rearrangement: Updated overall survival from an open-label, single-arm, multicenter Phase II study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT153.

The effect of nano-zirconia addition on the microstructure and properties of corundum castables was studied using corundum, kyanite, alumina powder, gel powder, and nano-ZrO2 as raw materials. The results showed that adding 1.2(wt)% nano-ZrO2 could reduce the median pore diameter of the castables from 480 to 200 nm at 110 °C. After the castables were heated at 1100 °C, the cold modulus of rupture increased by 29.95%, to 24.71 MPa, and the cold compressive strength increased by 50.32%, to 116.37 MPa. The hot modulus of rupture increased by 114.95%, to 3.59 MPa after being treatment at 1500 °C, the high surface energy of nano-ZrO2 can increase the interface energy and bonding strength between adjacent particles.

Biliary tract cancer (BTC) is an uncommon and aggressive neoplasm, with most patients presenting in an advanced stage. Systemic chemotherapy is the limited treatment available but is unsatisfactory, while targeted therapy is still awaiting validation from clinical trials. Given the potential effect of immune checkpoint inhibitors (ICIs) in the treatment of BTC, this review aims to summarize the evidence-based benefits and predictive biomarkers for using inhibitors of cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) ligand, or programmed cell death protein-1 and its ligand (PD-1 and PD-L1) as monotherapy or combined with other anti-tumor therapies, while also pointing out certain pitfalls with the use of ICIs which need to be addressed.

Energy management strategy is used to realize dynamic mode switching of hybrid electric vehicles, which can achieve good energy saving effect. However the vehicle future speed, road traffic flow information and other factors are unknown, excellent energy saving effect can’t be realised by the existing energy management strategy. Owe to the development of V2X, more information will be provided, a dynamic energy management strategy of hybrid electric vehicle (HEV) combining velocity prediction with dynamic optimization is proposed to deal with the complex and changeable problems of vehicle running process. The speed prediction layer, threshold optimization layer and strategy execution layer are included in this strategy. The LSTM is used to predict the vehicle speed based on V2X information in the speed prediction layer, so as to predict the future short-term torque demand of the vehicle. Based on the predicted vehicle speed curve, the LS-PSO algorithm is used in the threshold optimization layer to optimize the mode switching thresholds of the energy management strategy and the thresholds are transmited to the executive layer for vehicle energy allocation. After simulation verification, the results show that compared with the strategy of fixed rule, energy consumption of the dynamic energy management strategy is reduced. The average energy consumption in the ideal scenario can be reduced averagely by 22.1%.

Graphical abstract, Highlights • Protein profiling identified crucial genes that were used to screen related ncRNAs. • Both miRNAs and isomiRs were involved in coding-non-coding RNA regulatory network. • IsomiR-associated ceRNA networks implied the complex interactions among RNAs., Cholangiocarcinomas (CCAs) are tumors that arise from the cholangiocytes. Although some genes have been shown with important roles in pathological process, interactions or cross-talks among different RNAs are important to understand the detailed molecular mechanisms in cancer development, especially discussing cross-talks among isomiRs and other RNAs. Herein, to characterize crucial genes in CCA, the protein expression profile was performed to survey potential crucial mRNAs and related non-coding RNAs (ncRNAs) in mRNA-ncRNA network, mainly including miRNAs/isomiRs and lncRNAs. Deregulated mRNAs were firstly obtained if consistent expression patterns were found at protein and mRNA levels, and related miRNAs/isomiRs were screened according to regulatory relationships. Diverse isomiRs from a given miRNA locus also contributed to interactions between the small RNAs and target mRNAs, and miRNAs were further used to survey related lncRNAs to expand the interactions. Thus, several groups of RNAs were constructed as candidate competitive endogenous RNA (ceRNA) networks. Finally, we found that RAB11FIP1:miR-101-3p:MIR3142HG may be a potential ceRNA network, and the interactions among them may be more complex due to variety of isomiRs. Simultaneously, RAB11FIP1 and miR-194-5p were also detected other related lncRNAs (FBXL19-AS1, SNHG1 and PVT1) that may be crucial in coding-non-coding RNA regulatory network. Our results show that diverse isomiRs with sequence and expression heterogeneities contribute to ceRNA regulatory network that may have crucial roles in CCA, which will expand our understanding of interactions among diverse RNAs and their contributions in cancer development.

PurposeImmune checkpoint inhibitors plus antiangiogenic tyrosine kinase inhibitors may offer a first-line treatment for advanced hepatocellular carcinoma (HCC). In this phase 2 trial [registered with clinicaltrials.gov (NCT04052152)], we investigated the safety and efficacy of first-line anti-PD-1 antibody sintilimab plus antiangiogenic TKI anlotinib for advanced HCC.Methods and MaterialsPathologically-proven advanced HCC patients received sintilimab (200 mg) on day 1 and anlotinib (12 mg) once daily on days 1 to 14 every 3 weeks, with a safety run-in for the first six participants to assess dose-limiting toxicities (DLTs). The primary endpoints were safety and objective response rate (ORR) per RECIST v1.1.ResultsTwenty advanced HCC patients were enrolled. No DLTs occurred in the safety run-in. All patients had treatment-related adverse events (TRAEs). Grade 3 TRAEs occurred in 8 (40.0%) patients, the most common being decreased platelet count (10.0%) and increased γ-glutamyl transferase (10.0%). No grade 4/5 TRAEs occurred. Five (25%) patients developed immune-related AEs. The ORR was 35.0% (95%CI 15.4%-59.2%) per RECIST v1.1 and 55.0% (95%CI 31.5%-76.9%) per modified RECIST. At data cutoff (March 31, 2021), the median progression-free survival was 12.2 months (95%CI, 3.8 to not reached). The median PFS was significantly longer in patients with lower LDH levels (not reached [NR], 95% CI, 8.7 to NR vs. higher LDH levels 5.2 months, 95% CI 3.4 to NR; P=0.020) and a CONUT score ≤2 (NR, 95% CI 5.1 to NR vs. CONUT score >2 6.2 months, 95% CI 1.8 to NR; P=0.020). Furthermore, patients showing tumor response had a significantly higher median proportion of CD16+CD56+ NK cells than patients who had stable or progressive disease (21.6% vs. 14.6%; P=0.026).ConclusionSintilimab plus anlotinib showed promising clinical activities with manageable toxicity as first-line treatment of advanced HCC.

The work was to develop novel high temperature microwave absorbing material based MgZr4(PO4)6 (MZP) ceramic. The results show that thermal expansion process at higher temperature expand along c-axis while shrink along the a-axis. The conductivity of MZP ceramic was increased by 1000 orders due to the increase in magnesium ion mobility. In addition, the results indicates that the dielectric properties were dependent on temperature at all measured frequencies. The real and imaginary parts of dielectric constant increased from 4.0–5.2 and 0.024 to 0.4, respectively. The reflection loss varied with the change in thickness and the minimum reflection loss value was -26.66 dB at 800℃, suggesting that MZP ceramic was a promising novel high temperature microwave absorbing material.

A series of delaminated MWW-type Zr-Al-SCM-1 zeolites with large external surface area have been synthesized through a post-synthesized method by partial dealumination of SCM-1 and Zr incorporation based on parent SCM-1 zeolite, and used in the conversion of furfural and xylose to γ-valerolactone (GVL). The characterization of catalysts using XRD, FTIR, 29Si NMR, Raman, UV–vis and XPS spectroscopy confirmed the preservation of the parent SCM-1 zeolite network as well as the incorporation of Zr atoms into the zeolite framework with tetrahedral coordination. NH3-TPD and Py-FTIR spectroscopy reveal that the Zr-Al-SCM-1 zeolites possess both Bronsted and Lewis acid sites. When they are applied to the one-pot cascade conversion of furfural, a remarkable GVL yield of 47.3% with 85.6% carbon balance is obtained at 170 °C after 28 h. When considering xylose as starting substrate, up to 36.4% yield of GVL is achieved over Zr-Al-SCM-1 zeolites with excellent recyclability at 170 °C after 48 h. Moreover, the catalyst shows far superior catalytic performance and stability compared to the commercial MCM-22 based zeolites (Zr-Al-MCM-22).

The effects of in-situ synthesis columnar mullite and pore structure on the hot modulus of rupture (HMOR), thermal shock resistance and corrosion resistance of corundum castables have been investigated in this paper. When 2% nano silica was added, the pore diameters of castables could be decreased to 15 nm (at 110 °C), 1 μm (1100 °C) and 6 μm (1500 °C), respectively. The corresponding reducing magnitude of pore size is 98.5%, 83.3% and 33.3%. The HMOR of castables fired at 1500 °C increased by 110% to 3.64 MPa. Furthermore, after three thermal shock cycles, the residual strength ratio of castables increased from 5.2% to 15.3%. A large amount of cross-distributed columnar mullite was formed between nano silica and α-Al2O3 by the two-dimensional nucleation mechanism, which remarkably enhanced the high temperature properties. The penetration index reduced from 30.86% to 19.88%, suggesting that smaller pore size and higher viscosity had a great influence to the penetration process.

The effect of the particle size (50–325 mesh) and content (0–0.1 wt%) of metallic aluminum powder on the explosive spalling resistance of corundum-based refractory castables were investigated in this study based on air permeability, pore size distribution, heat release, fracture energy and microstructural analyses. The experimental results show that the addition of Al powder significantly improves their explosive spalling resistance. As observed, the explosive spalling resistance of the castables was mainly influenced by the permeability mechanism and the fracture energy. Permeable paths were generated in the microstructure of the sample during the overlapping period between the curing process and the H2 gas forming one, derived from the Al–H2O reaction. The highest permeability level was obtained when 0.075 wt % of Al powder with size of 100 mesh was incorporated into the corundum-based refractory castables. At the same time, the fracture energy of the castable samples was increased accordingly.

In this work, β-Sialon of different morphologies was generated using in situ morphological regulation and simulation. Their effects on the thermo-mechanical properties of Al2O3-C refractories were then investigated. The results indicate that columnar, plate-like, and hexagonal prism β-Sialon were formed from specimens without additives, with Fe2O3 as a catalyst, and with Ni as a catalyst, respectively. Transmission electron microscope (TEM) analysis results confirmed that the three morphologies of β-Sialon grow along with (110), (101), and (100), respectively. Density functional theory (DFT) results show that the addition of catalyst atoms could reduce the adsorption energy of gaseous Al2O on different crystal planes, which promotes the formation of β-Sialon. The formation of three different shapes of β-Sialon gave rise to materials with good mechanical strength. The cold modulus of rupture (CMOR) and cold crushing strength (CCS) of the specimen containing plate-like structure was slightly higher than those with a columnar and hexagonal prism, with maximum CMOR and CCS values of 27.2 MPa and 105.2 MPa, respectively. In addition, good thermal shock resistance was obtained due to the formation of β-Sialon; the residual strength ratio of the specimen with columnar β-Sialon was 78% after five thermal shock cycles, and those with plate-like and hexagonal prism reached 93% and 86%, respectively.