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Copyright of Rare Metals is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: To investigate whether prognosis of patients with hepatocellular carcinoma (HCC) is affected by the abundance and subgroups of myeloid-derived suppressor cells (MDSCs) as well as subtypes and expression of apolipoprotein E (apoE). Methods: 31 HCC patients were divided into three groups according to blood total apoE level for detecting the abundance of immunoregulatory cells by flow cytometry. Tumour tissue microarrays from 360 HCC patients were evaluated about the abundance and subgroups of MDSCs and the expression of apoE2, apoE3, apoE4 by immunofluorescence staining and immunohistochemistry staining. Survival analysis by means of univariate, multivariate COX regression and Kaplan-Meier methods of the 360 patients was performed based on clinical and pathological examinations along with 10 years’ follow-up data. Results: The lower apoE group presented higher abundance of MDSCs in the peripheral blood of HCC patients than higher apoE group. The abundance of monocyte-like MDSCs (M-MDSCs) was higher in the apoE low level group than high level group (p = 0.0399). Lower H-score of apoE2 (HR = 6.140, p = 0.00005) and higher H-score of apoE4 (HR = 7.001, p = 0.009) in tumour tissue were significantly associated with shorter overall survival (OS). The higher infiltration of polymorphonuclear granulocyte-like MDSCs (PMN-MDSCs, HR = 3.762, p = 0.000009) and smaller proportion of M-MDSCs of total cells (HR = 0.454, p = 0.006) in tumour tissue were independent risk factors for shorter recurrence-free survival (RFS). Conclusion: The abundance of MDSCs in HCC patients’ plasma negatively correlates with the level of apoE. The expression of apoE4 in HCC tissue indicated a poor prognosis while apoE2 might be a potential protective factor. [ABSTRACT FROM AUTHOR]

Background & aims: Patients with intrahepatic cholangiocarcinoma (iCCA) respond poorly to immune checkpoint blockades (ICBs). In this study, we aimed to dissect the potential mechanisms underlying poor response to ICBs and explore a rational ICB-based combination therapy in iCCA. Methods: scRNA-seq dataset GSE151530 was analyzed to investigate the differentially expressed genes in malignant cells following ICBs therapy. RNA-seq analysis and western blot assays were performed to examine the upstream and downstream signaling pathways of CD73. Subcutaneous tumor xenograft models were utilized to investigate the impact of CD73 on iCCA growth. Plasmid AKT/NICD-induced spontaneous murine iCCAs were used to explore the therapeutic efficacy of CD73 enzymatic inhibitor AB680 combined with PD-1 blockade. Time-of-flight mass cytometry (CyTOF) was conducted to identify the tumor-infiltrating immune cell populations and their functional changes in murine iCCAs treated with AB680 in combination with PD-1 antibody. Results: scRNA-seq analysis identified elevated CD73 expression in malignant cells in response to ICBs therapy. Mechanistically, ICBs therapy upregulated CD73 expression in malignant cells via TNF-α/NF-κB signaling pathway. In vivo studies revealed that CD73 inhibition suppressed the growth of subcutaneous tumors, and achieved synergistic depression effects with gemcitabine and cisplatin (GC). Adenosine produced by CD73 activates AKT/GSK3β/β-catenin signaling axis in iCCA cells. CD73 inhibitor AB680 potentiates anti-tumor efficacy of PD-1 antibody in murine iCCAs. CyTOF analysis showed that AB680 combined with anti-PD-1 therapy promoted the infiltration of CD8+ T, CD4+ T cells, and NK cells in murine iCCAs, while simultaneously decreased the proportions of macrophages and neutrophils. Moreover, AB680 combined with anti-PD-1 significantly upregulated the expression of Granzyme B, Tbet and co-stimulatory molecule ICOS in infiltrating CD8+ T cells. Conclusions: CD73 inhibitor AB680 limits tumor progression and potentiates therapeutic efficacy of GC chemotherapy or anti-PD-1 treatment in iCCA. AB680 combined with anti-PD-1 therapy effectively elicits anti-tumor immune response. [ABSTRACT FROM AUTHOR]

Purpose: Hepatocellular carcinoma (HCC) is a critical global health concern, with existing treatments benefiting only a minority of patients. Recent findings implicate the chemokine ligand 17 (CCL17) and its receptor CCR4 as pivotal players in the tumor microenvironment (TME) of various cancers. This investigation aims to delineate the roles of CCL17 and CCR4 in modulating the tumor’s immune landscape, assessing their potential as therapeutic interventions and prognostic markers in HCC. Methods: 873 HCC patients post-radical surgery from 2008 to 2012 at Zhongshan Hospital, Fudan University were retrospectively examined. These individuals were stratified into a training cohort (n = 354) and a validation cohort (n = 519). Through immunohistochemical analysis on HCC tissue arrays, the expressions of CCL17, CCR4, CD73, CD47, HHLA2, and PD-L1 were quantified. Survival metrics were analyzed using the Cox model, and a prognostic nomogram was devised via R software. Results: The investigation confirmed the presence of CCL17 and CCR4 within the cancerous and stromal compartments of HCC tissues, associating their heightened expression with adverse clinical markers and survival outcomes. Notably, the interplay between CD73 and CCR4 expression in tumor stroma highlighted a novel cellular entity, CCR4 + CD73 + stromal cells, impacting overall and relapse-free survival. A prognostic nomogram amalgamating these immunological markers and clinical variables was established, offering refined prognostic insights and aiding in the management of HCC. The findings suggest that reduced CCR4 and CCR4 + CD73 + cell prevalence may forecast improved outcomes post-TACE. Conclusion: This comprehensive evaluation of CCR4, CCL17, and associated markers introduces a nuanced understanding of the HCC immunological milieu, proposing CCR4 + CD73 + stromal cells as critical to HCC pathogenesis and patient stratification. [ABSTRACT FROM AUTHOR]

Copyright of Rare Metals is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: We sought to summarize the value of contrast-enhanced computed tomography (CECT) in the differential diagnosis of bladder paraganglioma (BPG) and bladder cancer. Methods: The medical records of 19 patients with BPG (13 males, 6 females) and 56 patients with bladder cancer (49 males, 7 females) between November 2007 and June 2023 were retrospectively reviewed. All patients underwent unenhanced and contrast-enhanced CT scanning. Results: Patient age (46.4 ± 11.1 years vs. 58.6 ± 16.0 years), tumor calcification (1/19 vs. 18/56), stalk (0/19 vs. 10/56), internal vessels (15/19 vs. 19/56) and the enlarged adjacent supplying artery (14/19 vs. 10/56) were significantly different between BPG and bladder cancer (P < 0.05). The CT value in the corticomedullary phase (92.4 ± 16.6 HU vs. 64.0 ± 14.5 HU) and the contrast-enhanced value in the corticomedullary phase (54.5 ± 17.4 HU vs. 28.5 ± 12.8 HU) were significantly greater in BPG patients than in bladder cancer patients (P < 0.001), with corresponding area under the curve values of 0.930 and 0.912, respectively. The optimal cutoff values were 83.2 HU and 38.5 HU, respectively. A CT value > 83.2 HU in the corticomedullary phase and a contrast-enhanced CT value > 38.5 HU in the corticomedullary phase were used to indicate BPG with sensitivities of 78.9% and 89.5%, respectively, and specificities of 94.6% and 75.0%, respectively. Conclusion: The corticomedullary phase of CECT plays an important role in the preoperative differential diagnosis of BPG and bladder cancer. [ABSTRACT FROM AUTHOR]

Introduction: A survival paradox between T4N0 (Stage IIB/IIC) and Stage IIIA colon cancer exists, even after adjusting for adequate lymph node (LN) retrieval and receipt of adjuvant chemotherapy (C). We conducted a large hospital-based study to re-evaluate this survival paradox based on the newest 8th edition staging system. Methods: The National Cancer Data Base was queried to evaluate 35,606 patients diagnosed with Stage IIB, IIC, and IIIA colon cancer between 2010 and 2017. The Kaplan–Meier method and log-rank test were used to compare unadjusted overall survival (OS). Multivariable Cox proportional hazards model was used to determine the association of stage with hazard ratios adjusted for relevant demographic and clinical variables including ≥ 12 LNs retrieved and receipt of adjuvant chemotherapy. P value < 0.05 was considered statistically significant. Results: The 5-year OS for optimally treated stage IIIA colon cancer (receipt of C) was 84.3%, which was significantly higher than stage IIB/C (≥ 12 LNs retrieved + C) (72.8%; P < 0.0001). Stage was an independent predictor of OS. Among optimally treated Stage IIIA patients, T1N1 had the best survival (90.6%) while stage T4bN0 (stage IIC) had the worst (70.9%) (P < 0.0001). Compared to stage IIB, stage IIC had a 17% increased risk of overall death while stage IIIA had a 21% reduction in death (P < 0.0001). Conclusion: Stage IIB/C and Stage IIIA survival paradox persists even after accounting for receipt of adjuvant chemotherapy and adequate lymph node retrieval. Future iteration of the TNM system should take this paradox into consideration. [ABSTRACT FROM AUTHOR]

Herringbone gear planetary gear transmission system has the advantages of high contact ratio and high bearing capacity and is widely used in various heavy load fields. However, the gear generates a large amount of heat during the meshing transmission, which affects the nonlinear dynamic characteristics of the system. In this paper, the various nonlinear factors are considered, including time-varying meshing stiffness, engagement damping, backlash, and engagement error. A nonlinear dynamic model of the herringbone planetary gear system considering temperature effects is established by using the lumped-parameter method. The nonlinear vibration differential equation of the system is solved by using the Runge–Kutta method. The impact law of temperature and engagement damping ratio changes on the bifurcation features of the herringbone planetary gear system is studied by combining the maximum Lyapunov exponent diagram, bifurcation diagram, time domain diagram, phase diagram, Poincare diagram, and spectrogram. And the chaos phenomenon of the system is analyzed and controlled by using a non-feedback control method with the external periodic signal. The result shows that with the change of temperature rise and meshing damping ratio, the system exhibits the kinematics response of chaotic, multi-period, and single-period. Higher temperature rise (∆T > 64 °C) and larger engagement damping ratio (ξ > 0.122) can make the gear system enter stable periodic motion. The chaotic motion region of the system is effectively controlled to the periodic motion orbit by introducing the periodic signal feedback controller. The relevant conclusions can provide a theoretical basis for the optimal design of the dynamic structure stability of herringbone planetary gear. [ABSTRACT FROM AUTHOR]

Due to the high theoretical specific capacity (1675 mAh·g–1), low cost, and high safety of the sulfur cathodes, they are expected to be one of the most promising rivals for a new generation of energy storage systems. However, the shuttle effect, low conductivity of sulfur and its discharge products, volume expansion, and other factors hinder the commercialization of lithium–sulfur batteries (LSBs). The development of sulfur-fixing materials and the design of multifunctional materials to enhance the electrochemical performance of LSBs have been the main research priorities in recent years. Because of the advantages of high conductivity, built-in electric field, and good synergism, more and more researchers have employed heterostructure into sulfur-fixing materials to enhance the catalytic and absorption ability for polysulfides. In this review, the principle of heterostructure and the mechanism of enhancing the performance of lithium–sulfur batteries are described. The applications of heterostructure in cathode and interlayer of LSBs in the latest years are summarized. Finally, the cutting-edge troubles and possibilities of heterostructures in LSBs are briefly presented. 摘要: 锂硫电池 (LSBs) 由于硫正极的高理论比容量 (1675 mAh·g–1), 成本低, 安全性高等优势, 有望成为新一代最有前途的储能系统之一. 然而, 穿梭效应, 硫及其放电产物的绝缘性, 体积膨胀等因素阻碍了LSBs的商业化进程. 开发固硫材料和设计多功能材料以提高LSBs的电化学性能, 是近年来的主要研究重点. 异质结构因具有高导电性, 内建电场和良好的协同作用等优点, 越来越多的研究人员将其引入到固硫材料中, 以增强固硫材料对多硫化物的吸附和催化能力. 在这篇综述中, 描述了异质结构的原理和增强锂硫电池性能的机制. 总结了近几年异质结构在LSBs正极和隔膜中的应用. 最后, 简要地提出了异质结构在LSBs中的前沿问题和可能性. [ABSTRACT FROM AUTHOR]

Heteroatom doping of carbon materials can effectively alter the microstructure and conductivity, thereby improving the electrochemical performance of lithium-ion batteries (LIBs) hard carbon anodes. Herein, a resin-based hard carbon material (NFHC-1200) with co-doped N and F was prepared by one-step pyrolysis method using phenolic resin as the carbon source and ammonium fluoride as the doped N and F sources. Benefiting from the synergistic effects of co-doping, NFHC-1200 exhibited a wider interlayer distance (0.385 nm), a larger specific surface area (93.31 m2 g−1), and a greater number of Li+ storage active sites (ID/IG = 1.754) when compared to undoped HC-1200 and single-atom doped NHC-1200 hard carbon materials. The results of electrochemical performance demonstrated that the electrochemical properties of NFHC-1200 was significantly improved for co-doped N and F. It exhibited an initial discharge capacity of 614.6 mAh g−1 at 37.2 mA g−1, a reversible capacity of 365.2 mAh g−1 with a capacity retention rate of 97.66% even after 150 cycles, and a rate performance of 131 mAh g−1 even at a high current density of 5C (1C = 372 mAh g−1), which were much higher than those observed from NHC-1200 and HC-1200 under the same test conditions. Overall, this work clearly clarifies the mechanism of N/F co-doping synergistic effects to enhance the electrochemical properties of hard carbon materials by comparing the differences in microstructure and electrochemical properties of NFHC-1200 with NHC-1200 and HC-1200, which may provide a new insight into the modification of hard carbon materials. [ABSTRACT FROM AUTHOR]

Purpose: Planetary gears generate a lot of heat during the meshing transmission process, which results in thermal deformation of the gear teeth and affects the nonlinear dynamic characteristics of the system. It is valuable to study the influence of the thermal effect on the chaotic characteristics of planetary gear systems. Method: Based on the law of thermal deformation, considering the temperature effect and multiple nonlinear factors, including the coupling effects of time-varying meshing stiffness, meshing error, and gear backlash, a nonlinear dynamics model of the planetary gear system is established. The system's differential equation is derived from the gear system dynamics theory and solved using the Runge–Kutta method. The impact law of temperature, time-varying stiffness coefficient, and damping ratio changes on the bifurcation features of the planetary gear system is studied by combining the maximum Lyapunov exponent diagram, bifurcation diagram, time domain diagram, phase diagram, Poincare diagram, and spectrogram. Results: The planetary gear system exhibits chaotic and rich bifurcation characteristics under the coupling effect of multiple nonlinear factors. With the increase in temperature, the system experiences a kinematic process of chaos-four period-two period-single period. As the time-varying stiffness coefficient changes, the system exhibits chaotic, three-periodic, and two-periodic motion states. The effect of the engagement damping ratio change on the nonlinear characteristics of the system is significant when the value of the temperature is in the range of 0 < ∆T < 68 °C. Conclusion: The chaotic motion of the system is weakened under higher temperature and larger damping ratio, which has an obvious effect on improving the system's stability. The pertinent conclusions can be used as future references for gear system development. [ABSTRACT FROM AUTHOR]

Background: To evaluate if there are differences in outcomes for patients with stage III colon cancer in those from urban vs. rural commuting areas. Methods: Data were evaluated on patients diagnosed with stage III colon cancer between 2012 and2018 from the Louisiana Tumor Registry. Patients were classified into rural and urban groups. Data on overall survival, time from diagnosis to surgery and time from surgery to chemotherapy, and sociodemographic factors (including race, age, and poverty level) were recorded. Results: Of 2652 patients identified, 2159 were urban (81.4%) and 493 rural (18.6%). No age difference between rural and urban patients (p = 0.56). Stage IIIB accounted for 66.7%, followed by IIIC (21.6%) and IIIA (11%), with a significant difference between rural and urban patients based on stage (p = 0.02). There was no difference in the extent of surgery (p = 0.34) or tumor size (p = 0.72) between urban and rural settings. No difference in undergoing chemotherapy (p = 0.12). There was a statistically significant difference in receiving timely treatment for hospital volume (p < 0.0001) and poverty level (p < 0.0001), but no difference in time from diagnosis to surgery (p = 0.48), and time from surgery to chemotherapy (p = 0.27). Non-Hispanic Blacks were less likely to receive timely treatment when compared with non-Hispanic Whites for both surgery and adjuvant chemotherapy, (aHR 0.91, 95% CI 0.83–0.99) and (aHR 0.86, 95% CI 0.77–0.97), respectively. There was no difference in Kaplan–Meier overall survival curves comparing rural vs. urban patients (p = 0.77). Conclusions: There was no statistical difference in overall survival, time to surgery, and time to adjuvant chemotherapy between rural and urban patients with Stage III colon cancer. [ABSTRACT FROM AUTHOR]

Background: Relapse of hepatocellular carcinoma (HCC) due to vascular invasion is common, but the genomic mechanisms remain unclear, and molecular determinants of high-risk relapse cases are lacking. We aimed to reveal the evolutionary trajectory of microvascular invasion (MVI) and develop a predictive signature for relapse in HCC. Methods: Whole-exome sequencing was performed on tumor and peritumor tissues, portal vein tumor thrombus (PVTT), and circulating tumor DNA (ctDNA) to compare the genomic profiles between 5 HCC patients with MVI and 5 patients without MVI. We conducted an integrated analysis of exome and transcriptome to develop and validate a prognostic signature in two public cohorts and one cohort from Zhongshan Hospital, Fudan University. Results: Shared genomic landscapes and identical clonal origins among tumor, PVTT, and ctDNA were observed in MVI (+) HCC, suggesting that genomic changes favoring metastasis occur at the primary tumor stage and are inherited in metastatic lesions and ctDNA. There was no clonal relatedness between the primary tumor and ctDNA in MVI (–) HCC. HCC had dynamic mutation alterations during MVI and exhibited genetic heterogeneity between primary and metastatic tumors, which can be comprehensively reflected by ctDNA. A relapse-related gene signature named RGSHCC was developed based on the significantly mutated genes associated with MVI and shown to be a robust classifier of HCC relapse. Conclusions: We characterized the genomic alterations during HCC vascular invasion and revealed a previously undescribed evolution pattern of ctDNA in HCC. A novel multiomics-based signature was developed to identify high-risk relapse populations. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress induced growth inhibitor 1 (OSGIN1) regulates cell death. The role and underlying molecular mechanism of OSGIN1 in non-small cell lung cancer (NSCLC) are uncharacterized. Methods: OSGIN1 expression in NSCLC samples was detected using immunohistochemistry and Western blotting. Growth of NSCLC cells and gefitinib-resistant cells expressing OSGIN1 or TUBB3 knockdown was determined by MTT, soft agar, and foci formation assays. The effect of OSGIN1 knockdown on in vivo tumor growth was assessed using NSCLC patient-derived xenograft models and gefitinib-resistant patient-derived xenograft models. Potentially interacting protein partners of OSGIN1 were identified using IP-MS/MS, immunoprecipitation, PLA, and Western blotting assays. Microtubule dynamics were explored by tubulin polymerization assay and immunofluorescence. Differential expression of signaling molecules in OSGIN1 knockdown cells was investigated using phospho-proteomics, KEGG analysis, and Western blotting. Results: We found that OSGIN1 is highly expressed in NSCLC tissues and is positively correlated with low survival rates and tumor size in lung cancer patients. OSGIN1 knockdown inhibited NSCLC cell growth and patient-derived NSCLC tumor growth in vivo. Knockdown of OSGIN1 strongly increased tubulin polymerization and re-established gefitinib sensitivity in vitro and in vivo. Additionally, knockdown of TUBB3 strongly inhibited NSCLC cell proliferation. Mechanistically, we found that OSGIN1 enhances DYRK1A-mediated TUBB3 phosphorylation, which is critical for inducing tubulin depolymerization. The results of phospho-proteomics and ontology analysis indicated that knockdown of OSGIN1 led to reduced propagation of the MKK3/6-p38 signaling axis. Conclusions: We propose that OSGIN1 modulates microtubule dynamics by enhancing DYRK1A-mediated phosphorylation of TUBB3 at serine 172. Moreover, elevated OSGIN1 expression promotes NSCLC tumor growth and gefitinib resistance through the MKK3/6-p38 signaling pathway. Our findings unveil a new mechanism of OSGIN1 and provide a promising therapeutic target for NSCLC treatment in the clinic. [ABSTRACT FROM AUTHOR]

The design of a random copolymer comprising of 4-vinylbenzocyclobutene (4VBCB) and styrene as repeating units is presented herein. The effect of the 4VBCB to styrene ratio in the copolymer on the dielectric and thermodynamic properties of the materials was investigated using the molecular dynamics simulation technique. A script for the interactive crosslink relaxation method was developed using Perl as the language to control the crosslinking degree of the copolymers. This method was used to construct simulation units to generate highly crosslinked polymer networks from a given set of monomers. Three-dimensional simulation cells were constructed with the help of a computational algorithm and Materials Studio. The dielectric constants of the model were calculated using the existing polymer COMPASS force field by varying the monomer contents. The crosslinking degree was tuned to analyze the material properties. Several thermomechanical properties, such as curing-induced shrinkage, coefficient of thermal expansion, and glass transition temperature, were analyzed, and their dependence on the crosslinking degree was examined. The simulation results revealed that an increase in the crosslinking density resulted in an increase in the dielectric constant and glass transition temperature of the material. The extent of thermal expansion realized decreased under these conditions. The reliability of the simulation results was confirmed by comparing these results with experimentally-obtained results. The theoretically and experimentally obtained results demonstrated a close match within the acceptable error range. [ABSTRACT FROM AUTHOR]

Lithium-sulfur batteries are a promising candidate for next-generation energy storage due to their high theoretical energy density. However, S insulation and the lithium polysulfide intermediate's shuttle effect greatly hinder its practical application. In this paper, a three-dimensional porous graphene oxide (GO)/MXene (Ti3C2Tx) (GM) aerogel is designed and applied to a lithium–sulfur battery to settle the problem mentioned. In this strategy, two-dimensional (2D) GO sheets and highly conductive MXene nanosheets are integrated to form a 3D porous aerogel structure, creating a 3D conductive network and large polar surfaces, which can simultaneously achieve fast Li-ion/electron transport, strong chemical anchoring sulfur, and promot redox reactions between polysulfides. Therefore, the cathode shows excellent sulfur utilization and cycle stability. The prepared GM electrode battery has been tested for nearly nine months at 0.1C, providing the high initial capacity of 1255.62 mAh·g−1 and maintaining 615.7 mAh·g−1 after 450 cycles. [ABSTRACT FROM AUTHOR]

Cold recycling method minimizes the need for aggregates while building roads and has significant economic and environmental benefits. The cold recycled mixture's inadequate mechanical strength, however, is a significant flaw. This article presents the strength increase equation after first analyzing the increasing law of the mechanical strength of the emulsified asphalt cold recycled mixture. The mechanical strength, high-temperature performance and low-temperature performance of emulsified asphalt cold recycled mixture have all been examined after the use of cement and fiber. The reinforcing effect of the fiber is also confirmed through field testing. Studies have shown that after 48 h, the mechanical properties of the emulsified asphalt cold recycled mixture become stable, and the increase is small. The correlation between the proposed strength growth equation and the laboratory test results reaches 0.99. With the addition of 1.5% cement, the high-temperature performance and low-temperature performance of asphalt mixture can be improved by 33% and 18%, respectively. The 0.4% of fiber can improve the high-temperature performance and low-temperature performance of asphalt mixture by 6% and 19%, respectively. Analyze the effect of cement and fiber on the performance of the emulsified asphalt cold recycled mixture, and choose the optimal content of cement and emulsified asphalt to be 1.5% and 0.4%, respectively. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancers (NSCLC) frequently contain KRAS mutation but retain wild-type TP53. Abundant senescent cells are observed in premalignant but not in malignant tumors derived from the Kras-driven mouse model, suggesting that KRAS oncogenic signaling would have to overcome the intrinsic senescence burden for cancer progression. Here, we show that the nuclear Beclin 1-mediated inhibition of p53-dependent senescence drives Kras-mediated tumorigenesis. KRAS activates USP5 to stabilize nuclear Beclin 1, leading to MDM2-mediated p53 protein instability. KrasG12D mice lacking Beclin 1 display retarded lung tumor growth. Knockdown of USP5 or knockout of Becn1 leads to increased senescence and reduced autophagy. Mechanistically, KRAS elevates ROS to induce USP5 homodimer formation by forming the C195 disulfide bond, resulting in stabilization and activation of USP5. Together, these results demonstrate that activation of the USP5-Beclin 1 axis is pivotal in overriding intrinsic p53-dependent senescence in Kras-driven lung cancer development. Oncogene-induced senescence (OIS) occurs in premalignant lung adenomas, but infrequently in malignant adenocarcinomas. Here the authors show that USP5-Beclin 1 axis overcomes OIS in Kras-driven lung cancer by enhancing MDM2-mediated p53 degradation. [ABSTRACT FROM AUTHOR]

Background: CXCL11 has been reported to be up-regulated in hepatocellular carcinoma (HCC) tissues and cancer-associated fibroblasts (CAFs), and CAF-secreted CXCL11 has been found to promote HCC cell proliferation and migration. Knowledge on how CAFs promote HCC progression is imperative for the future design of anti-tumor drugs addressing the high rates of disease recurrence. Herein, we propose a mechanism by which LINC00152 positively regulates CXCL11 expression and, subsequently, HCC cell phenotypes and growth characteristics via miR-205-5p in CAFs. Methods: The expression of LINC00152, miR-205-5p in HCC/non-cancerous tissues, CAFs/NFs and HCC cell lines was determined by RT-qPCR. The CXCL11 expression and secretion were determined by westernblot and ELISA. Different expressions of LINC00152, CXCL11 and miR-205-5p in CAFs were achieved by transfection with corresponding overexpression/knockdown vectors or mimics/inhibitor. The interactions among LINC00152, miR-205-5p and CXCL11 were confirmed by FISH, luciferase, AGO2 and RNA-pulldown assays. Transwell, colony formation and MTT assays were performed to assess the role of CAFs conditioned medium (CM) in HCC cell phenotype. BALB/c nude mice xenografts were used to determine the role of CAFs on HCC growth in vivo. Results: We found that in vitro, CM from CAFs transfected with sh-LINC00152 dramatically suppressed HCC cell viability, colony formation and migration, and that CM from CAFs transfected with miR-205-5p inhibitor (CAF-CM (miR-205-5p inhibitor)) exerted opposite effects on HCC cell phenotypes. Exogenous overexpression of CXCL11 in CAFs or CAF-CM (miR-205-5p inhibitor) could partially attenuate the effects of LINC00152 knockdown. In contrast, CM from CAFs transfected with LINC00152 dramatically increased HCC cell viability, colony formation and migration, and CM from CAFs transfected with miR-205-5p mimics (CAF-CM (miR-205-5p mimics)) exerted opposite effects on HCC cell phenotypes. Knockdown of CXCL11 in CAFs or CAF-CM (miR-205-5p mimics) could partially attenuate the effects of LINC00152 overexpression. In vivo, LINC00152 knockdown in CAFs inhibited tumor growth in a mouse model, which could be reversed by CXCL11 overexpression in CAFs. Mechanistically, we found that LINC00152 could act as a ceRNA to counteract miR-205-5p-mediated suppression on CXCL11 by directly binding to miR-205-5p and the 3'UTR of CXCL11. Conclusion: Our data indicate that a LINC00152/miR-205-5p/CXCL11 axis in HCC CAFs can affect the proliferative and migrative abilities of HCC cells in vitro and HCC tumor growth in vivo. [ABSTRACT FROM AUTHOR]

Copyright of Rare Metals is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In this study, a novel approach was presented for controllable preparation of polyacrylonitrile (PAN) hollow microspheres, and PAN-derived graphite carbon microspheres were synthesized through a simple and facile method, overcoming the intrinsic non-graphitizable property of PAN under low temperatures. The pure PAN microspheres and PAN/M (M = Fe, Co, Ni) microspheres were fabricated by the microfluidic technique and solvent evaporation method. Subsequently, the graphitization process was performed for carbon growth of all PAN microspheres at carbonization temperatures of 800 °C, 1000 °C,1200 °C, and 1400 °C, respectively. The effects of transition metals on the stability of compound droplets, monodispersity, and morphology of microspheres were investigated. The carbon resides was given by TG analysis, and the degree of graphite was characterized by the Raman spectra, XRD patterns, and TEM image. The results showed that the three transition metals exhibited different catalytic graphitization effects, leading to a different degree of catalytic graphitization. Understanding the catalytic graphitization effect of Fe, Co, and Ni on PAN microspheres offers new strategies for converting polymer-derived microspheres to invaluable synthetic graphite carbon, which has potential application in upcycling of waste plastics, catalysis, absorption, thermally conductive materials, and energy conversion. [ABSTRACT FROM AUTHOR]

In this work, the mechanical properties of compacted loess specimens formed using the vertical vibration compaction method (VVCM) were investigated, including unconfined compressive strength, CBR value, and shear strength. The top water seepage test and slope simulated rainfall test were implemented. In the test section, the water infiltration laws of compacted loess subgrades with different degrees of compaction were studied. Subsequently, the water stability of compacted loess subgrades was investigated. The results show that the loess specimens formed using the VVCM have adequate mechanical properties. Moreover, increasing the degree of compaction significantly improves the resistance of the loess roadbed to water infiltration and reduces both the water infiltration area and the corresponding water content. In addition, the seepage of the loess roadbed causes the roadbed to collapse, which affects the roadbed's stability. The high-compacted roadbed section exhibits improved resistance to collapse. Thus, improving roadbed compaction can effectively improve the roadbed's stability. [ABSTRACT FROM AUTHOR]

Carbon-supported platinum-nickel alloy catalysts have become one of the main choices of proton exchange membrane fuel cells (PEMFCs) due to the high catalytic activity toward oxygen reduction reaction (ORR). In this work, carbon aerogel supported platinum-nickel solid solution alloy catalysts (Pt3Ni/CA) with small particles (~ 3.5 nm) and uniform distribution were prepared via a simple one-step rapid reduction method during which no structure guide or stabilizer is added. In rotating disk electrode (RDE), the mass activity (MA, 0.25 A mgPt−1) and specific activity (SA, 4.69 A m−2) of the optimized Pt3Ni/CA catalysts for ORR are nearly 3.8 times and 6.5 times that of the state-of-the-art commercial carbon-supported platinum catalysts (Pt/C, 0.07 A mgPt−1 and 0.72 A m−2), respectively. After the accelerated durability test (ADT), the as-prepared Pt3Ni/CA catalysts still keep a satisfactory MA and SA which are more than 3.4 and 8.9 times as high as that of Pt/C. The Koutecký-Levich (K-L) equation shows that the electrochemical reaction conforms to be a 4e− process. [ABSTRACT FROM AUTHOR]

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Purposes: Our study aimed to examine the impact of diabetes, smoking and BMI on pancreatic cancer survival in a population-based setting by adjusting both sociodemographic and clinical factors and measuring their attributable risk. Methods: Data on pancreatic adenocarcinoma patients diagnosed in 2011–2017 were acquired from the Louisiana Tumor Registry. Diabetes, smoking, height, and weight were abstracted from medical records and linked with Hospital Inpatient Discharge Data to enhance the completeness of the diabetes data. The Cox regression model was used to assess effect sizes of diabetes, smoking, and BMI on cancer-specific survival and survival rate. The partial population attributable risk was employed to measure the attributable risk of these risk factors. Results: Of the 3,200 eligible patients, 34.6% were diabetics, 23.9% were current smokers, and 52.3% had BMI ≥ 25 kg/m2. After adjusting for sociodemographic and clinical factors, diabetic patients had an increased cancer-specific death risk of 15% (95% CI, 1.06–1.25), 36% (95% CI, 1.19–1.44) for current smokers, and 24% (95% CI, 1.00–1.54) for patients with a BMI ≥ 40 when compared to their counterparts. Diabetic current smokers had significantly lower 2- and 3-year adjusted cancer-specific survival rates, 13.1% and 10.5%, respectively. By eliminating diabetes and modifiable risk factors, an estimated 16.6% (95% CI, 6.9%–25.9%) of the cancer-specific deaths could be avoided during a nine-year observational period between 2011 and 2019. Conclusions: Diabetes and smoking contributed substantially to the reduction of pancreatic cancer survival even after controlling for sociodemographic and clinical factors; however, BMI ≥ 35 was observed to increase risk of mortality among stage III–IV patients only. [ABSTRACT FROM AUTHOR]

Long-term variation of nitrate in the East Sea was monitored in order to investigate impact of Three Gorges Dam (TGD) in the Changjiang River's upstream, China and Nakdong River's estuary dam, Korea. Tracing source of nitrate was another objective in this study. For this study, nutrient data were collected for 20 years from 1999 to 2018 in the East Sea, and divided into 4 sections, and evaluated whether a significant difference exists among the averages of nitrate concentrations. The concentrations of nitrate were affected by the major rivers (the Nakdong and the Taehwa Rivers) and Tsushima Warm Current (TWC) which diverged from the Kuroshio Current passing through East China Sea (ECS). Our results also indicated that long-term nitrate concentrations decreased and its reasons. First, the construction of TGD in the upstream of the Changjiang River may have resulted in the decrease of the nitrate supply in the river and ECS which is carried by TWC, toward the East Sea. Second, decrease in the nitrate flux of the Nakdong River's estuary due to the construction of the estuary dam and sewer treatment plant could also be a factor for the nitrate decrease in the East Sea. Therefore, anthropogenic activities from the Nakdong River and Changjiang River had a long-term effect on the East Sea's nitrate concentrations. The amount of nitrate runoff reduced by the anthropogenic activities influenced the nitrate levels over a long period by the flow of currents in the East Sea. [ABSTRACT FROM AUTHOR]

Abnormal activation of epidermal growth factor receptor (EGFR) drives non-small cell lung cancer (NSCLC) development. EGFR mutations-mediated resistance to tyrosine-kinase inhibitors (TKIs) is a major hurdle for NSCLC treatment. Here, we show that F-box protein FBXL2 targets EGFR and EGFR TKI-resistant mutants for proteasome-mediated degradation, resulting in suppression of EGFR-driven NSCLC growth. Reduced FBXL2 expression is associated with poor clinical outcomes of NSCLC patients. Furthermore, we show that glucose-regulated protein 94 (Grp94) protects EGFR from degradation via blockage of FBXL2 binding to EGFR. Moreover, we have identified nebivolol, a clinically used small molecule inhibitor, that can upregulate FBXL2 expression to inhibit EGFR-driven NSCLC growth. Nebivolol in combination with osimertinib or Grp94-inhibitor-1 exhibits strong inhibitory effects on osimertinib-resistant NSCLC. Together, this study demonstrates that the FBXL2-Grp94-EGFR axis plays a critical role in NSCLC development and suggests that targeting FBXL2-Grp94 to destabilize EGFR may represent a putative therapeutic strategy for TKI-resistant NSCLC. Aberrant EGFR activation is commonly found in non-small cell lung cancer (NSCLC). Here the authors show that E3 ubiquitin ligase FBXL2 targets EGFR and EGFR tyrosine kinase inhibitor (TKI)-resistant mutants for proteasome-mediated degradation to inhibit EGFR-driven NSCLC growth and TKI resistance. [ABSTRACT FROM AUTHOR]