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To investigate the nonlinear flutter characteristics of long-span suspension bridges under different deck ancillary structures and configurations, including those with and without a central wind-permeable zone, as well as to analyze the hysteresis phenomenon of a subcritical flutter and elucidate the mechanisms leading to the occurrence of nonlinear flutter, this paper studies first the post-flutter characteristics of the torsion single-degree-of-freedom (SDOF) test systems and vertical bending–torsion two-degree-of-freedom (2DOF) test systems under different aerodynamic shape conditions are further analyzed, and the role of the vertical vibration in coupled nonlinear flutter is discussed. The results indicate that better flutter performance is achieved in the absence of bridge deck auxiliary structures with a central wind-permeable zone. The participation of vertical vibrations in the post-flutter vibration increases with the increase in wind speed, reducing the flutter performance of the main girder. Furthermore, the hysteresis phenomenon in the subcritical flutter state is observed in the wind tunnel experiment, and its evolution law and mechanism are discussed from the perspective of amplitude-dependent damping. Finally, the vibration-generating mechanism of the limit oscillation ring is elaborated in terms of the evolution law of the post-flutter vibration damping.

The present study aims to investigate the influence of geometric nonlinearity on post-flutter responses by developing a full-mode coupled nonlinear flutter analysis method (frequency-domain method) and a time-dependent nonlinear analysis scheme (time-domain method). This approach integrates the three-dimensional (3D) nonlinear finite element model and nonlinear self-excited force described by amplitude-dependent rational functions (RFs). By comparing post-flutter responses obtained from frequency-domain and time-domain methods, not only the influence of geometric nonlinearity on post-flutter responses is quantified, but also the underlying physical mechanism is revealed. The results show that the geometric nonlinear effect will become more significant with the increase of the amplitude and thus will induce a super-harmonic resonance behavior. The behavior is mainly characterized by the higher harmonic frequencies vibrations with higher-order mode shapes involved in the vertical and torsional displacement responses. Meanwhile, the larger the vibration amplitude, the more significant the super-harmonic resonance behavior. Besides, the geometric nonlinear effect will also cause a significant uplifting of the bridge deck in the vertical direction during 3D nonlinear flutter process. The main physical mechanism for the reduction in the amplitude of post-flutter response (dominated by the vibration with fundamental harmonic frequency) after considering the geometric nonlinear behavior is that the vibrations with higher harmonic frequencies play a role of absorbing energy and reducing vibration (similar to tuned mass damper effect) for the vibration with fundamental harmonic frequency. For the long-span suspension bridge with a main span of 1650 m studied in this study, the geometric nonlinear effect may need to be considered when the torsional amplitude at mid-span is only greater than 1.5°.

The stromal cell derived factor (SDF)-1/chemokine receptor (CXCR)-4 signaling pathway plays a key role in lung cancer metastasis and is molecular target for therapy. In the present study we investigated whether interleukin (IL)-24 can inhibit the SDF-1/CXCR4 axis and suppress lung cancer cell migration and invasion in vitro. Further, the efficacy of IL-24 in combination with CXCR4 antagonists was investigated. Human H1299, A549, H460 and HCC827 lung cancer cell lines were used in the present study. The H1299 lung cancer cell line was stably transfected with doxycycline-inducible plasmid expression vector carrying the human IL-24 cDNA and used in the present study to determine the inhibitory effects of IL-24 on SDF-1/CXCR4 axis. H1299 and A549 cell lines were used in transient transfection studies. The inhibitory effects of IL-24 on SDF1/CXCR4 and its downstream targets were analyzed by quantitative RT-PCR, western blot, luciferase reporter assay, flow cytometry and immunocytochemistry. Functional studies included cell migration and invasion assays. Endogenous CXCR4 protein expression levels varied among the four human lung cancer cell lines. Doxycycline-induced IL-24 expression in the H1299-IL24 cell line resulted in reduced CXCR4 mRNA and protein expression. IL-24 post-transcriptionally regulated CXCR4 mRNA expression by decreasing the half-life of CXCR4 mRNA (>40%). Functional studies showed IL-24 inhibited tumor cell migration and invasion concomitant with reduction in CXCR4 and its downstream targets (pAKTS473, pmTORS2448, pPRAS40T246 and HIF-1α). Additionally, IL-24 inhibited tumor cell migration both in the presence and absence of the CXCR4 agonist, SDF-1. Finally, IL-24 when combined with CXCR4 inhibitors (AMD3100, SJA5) or with CXCR4 siRNA demonstrated enhanced inhibitory activity on tumor cell migration. IL-24 disrupts the SDF-1/CXCR4 signaling pathway and inhibits lung tumor cell migration and invasion. Additionally, IL-24, when combined with CXCR4 inhibitors exhibited enhanced anti-metastatic activity and is an attractive therapeutic strategy for lung metastasis.

Autophagy-dependent cisplatin resistance poses a challenge in bladder cancer treatment. SIRT1, a protein deacetylase, is involved in autophagy regulation. However, the precise mechanism through which SIRT1 mediates cisplatin resistance in bladder cancer via autophagy remains unclear. In this study, we developed a cisplatin-resistant T24/DDP cell line to investigate this mechanism. The apoptosis rate and cell viability were assessed using flow cytometry and the CCK8 method. The expression levels of the relevant RNA and protein were determined using RT-qPCR and a Western blot analysis, respectively. Immunoprecipitation was utilized to validate the interaction between SIRT1 and Beclin1, as well as to determine the acetylation level of Beclin1. The findings indicated the successful construction of the T24/DDP cell line, which exhibited autophagy-dependent cisplatin resistance. Inhibiting autophagy significantly reduced the drug resistance index of these cells. The T24/DDP cell line showed a high SIRT1 expression level. The overexpression of SIRT1 activated autophagy, thereby further promoting cisplatin resistance in the T24/DDP cell line. Conversely, inhibiting autophagy counteracted the cisplatin-resistance-promoting effects of SIRT1. Silencing SIRT1 led to increased acetylation of Beclin1, the inhibition of autophagy, and a reduction in the cisplatin resistance of the T24/DDP cell line. Introducing a double mutation (lysine 430 and 437 to arginine, 2KR) in Beclin-1 inhibited acetylation and activated autophagy, effectively reversing the decreased cisplatin resistance resulting from SIRT1 silencing. In summary, our study elucidated that SIRT1 promotes cisplatin resistance in human bladder cancer T24 cells through Beclin1-deacetylation-mediated autophagy activation. These findings suggest a potential new strategy for reversing cisplatin resistance in bladder cancer.

Background A significant challenge in bladder cancer treatment is primary chemoresistance, in which cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) play a pivotal role. While the contributions of CAFs to tumor progression and drug resistance are well established, the precise molecular mechanisms by which they induce chemoresistance remain unclear. A comprehensive understanding of the effect of TME modulation—particularly through CAFs—on the chemotherapeutic response is crucial for developing effective strategies to overcome chemoresistance and improve patient survival. Methods Primary fibroblasts were isolated from paired clinical samples of bladder cancer tissues and adjacent normal tissues to identify key CAF-derived secretory factors. Bioinformatics analysis, semiquantitative RT‒qPCR, and dual-luciferase reporter assays were subsequently used to investigate the functional role and mechanistic basis of CXCL14 in chemoresistance. The therapeutic relevance of these findings was further evaluated through in vitro and in vivo models, including ex vivo patient-derived organoid (PDO) models, by assessing cisplatin sensitivity and validating therapeutic targeting of the CXCL14-CCR7-STAT3 axis with small molecule inhibitors. Results Compared to normal fibroblasts and CAFs from nonchemoresistance groups, CAFs derived from cisplatin-resistant patients demonstrated significantly greater paracrine-mediated induction of chemoresistance. Mechanistically, CAF-secreted CXCL14 engaged CCR7 on bladder cancer cells, triggering STAT3 phosphorylation and consequently upregulating the DNA repair gene ERCC4 to promote cisplatin resistance. In vivo validation confirmed that pharmacological CCR7 or STAT3 inhibition markedly reversed chemoresistance and potentiated cisplatin-induced tumor cell death. Notably, STAT3 activation mediated the overexpression of the glycolytic enzymes HK2 and LDHA, resulting in greater glycolytic flux in resistant cells. This metabolic reprogramming further facilitated the transdifferentiation of normal fibroblasts into CXCL14-secreting CAFs, establishing a self-reinforcing feedback loop that sustains chemoresistance. Conclusion The CXCL14/CCR7/STAT3 axis critically mediates cisplatin resistance in bladder cancer through dual modulation of DNA repair and glycolytic metabolism. Therapeutic cotargeting of this pathway with CCR7 or STAT3 inhibitors combined with cisplatin represents a promising strategy to overcome chemoresistance and improve clinical outcomes.

Nucleolar protein 3 (NOL3), as a markedly increased protein across a range of tumors, has been well acknowledged that plays an anti-apoptotic role in malignancies, while some novel impacts of NOL3 on metastasis and chemoresistance are demonstrated recently. In this study, we uncover another role of NOL3 on promoting proliferation in bladder cancer (BLCA). The reduction of NOL3 significantly inhibited cell proliferation, and we detected the stable cell cycle arrest after knockdown of NOL3 in two-type BLCA cell lines. Mechanistically, we present the first evidence that the PI3K/Akt pathway was considerably inhibited with the decrease of NOL3 in BLCA cell lines. In addition, LY294002, a PI3K inhibitor, rescued NOL3 overexpression-mediated activation of the PI3K/Akt axis and the depression of proliferation in BLCA cell lines. In conclusion, our study suggests that NOL3 is upregulated in BLCA cells and promotes proliferation via the PI3K/Akt pathway, indicating that NOL3 may be a potential therapeutic target for BLCA.

The emission index of sulfur dioxide in the exhaust gas of the ceramic industry is an important indicator of the green production of enterprises and the green development of society. This article analyzes the emission sources of sulfur dioxide in the exhaust gas of the ceramic industry, and gives the calculation method for calculating the sulfur dioxide emissions in raw materials and fuels. At the same time, it compares the two-alkali wet desulfurization, limestone-gypsum wet desulfurization, and semi-dry desulfurization. The three governance measures provide references for ceramic companies to evaluate sulfur dioxide emissions and treatment.

Microgeographic adaptation is a fundamental driving force of evolution, but the underlying causes remain undetermined. Here, the phenotypic, genomic and transcriptomic variations of two wild barley populations collected from sharply divergent and adjacent micro‐geographic sites to identify candidate genes associated with edaphic local adaptation are investigated. Common garden and reciprocal transplant studies show that large phenotypic differentiation and local adaptation to soils occur between these populations. Genetic, phylogenetic and admixture analyses based on population resequencing show that significant genetic divergences occur between basalt and chalk populations. These divergences are consistent with the phenotypic variations observed in the field. Genome sweep analyses reveal 162.7 Mb of selected regions driven by edaphic local adaptation, in which 445 genes identified, including genes associated with root architecture, metal transport/detoxification, and ABA signaling. When the phenotypic, genomic and transcriptomic data are combined, HvMOR, encoding an LBD transcription factor, is determined to be the vital candidate for regulating the root architecture to adapt to edaphic conditions at the microgeographic scale. This study provides new insights into the genetic basis of edaphic adaptation and demonstrates that edaphic factors may contribute to the evolution and speciation of barley. Massive variations are observed on the phenotypic traits, genomic diversity, and transcriptomic dynamics of the two wild barley populations collected from sharply divergent and adjacent microgeographic sites. HvMOR was found to regulate the root architecture of wild barley to adapt to basalt and chalk edaphic conditions. This study sheds light on the genetic mechanism of microgeographic adaption and genomic divergence associated sympatric speciation in barley and beyond.

R711.75; 目的 报道5例原发性卵巢甲状腺肿类癌的临床病理特征及治疗方式并进行文献复习,以提高对该病的认识.方法 回顾性分析2009年1月-2020年12月浙江大学医学院附属金华医院收治的3例及东阳市人民医院收治的2例原发性卵巢甲状腺肿类癌患者的临床资料、镜下形态、免疫组织化学表型.结合文献报道的28例患者,总结原发性卵巢甲状腺肿类癌的临床病理特点及治疗方式.结果 例1和例5为原发性卵巢甲状腺肿类癌,例2和例4为原发性卵巢甲状腺肿类癌合并囊性畸胎瘤(其中例2尚伴黏液型类癌),例3为原发性卵巢甲状腺肿类癌伴黏液型类癌.5例患者甲状腺肿类癌的甲状腺滤泡成分免疫组织化学染色均呈甲状腺标记物阳性,类癌成分免疫组织化学染色均呈神经内分泌标记物及生长抑素受体2(SSTR2)阳性,例2和例3中黏液型类癌均呈突触素(Syn)阳性、嗜铬素A(CgA)阳性、CDX2阳性.5例患者肿瘤Ki-67增殖指数均<2％.此外,5例患者的甲状腺滤泡不同程度地表达神经内分泌标记物.4例术后随访未发现肿瘤复发转移,1例失访.在PubMed和SEER数据库分别检索了1971-2021年和1988-2011年报道的原发性卵巢甲状腺肿类癌病例,共28例,患者平均年龄分别为51岁和46岁,除1例出现淋巴结转移和1例死亡外,其余在随访期间均未发现肿瘤复发转移.结论 原发性卵巢甲状腺肿类癌是一种罕见的卵巢肿瘤,部分病例可伴囊性畸胎瘤及黏液型类癌,常缺少典型的临床表现,病理取材及诊断时应避免漏诊.Ⅰ期患者可选择保留更多脏器功能的手术方式,预后较好,但需长期随访以排除复发及隐匿转移.

T函数是由Klimov和Shamir在2002年提出的一类新的非线性函数, 因其天然具有复杂的非线性结构, 软硬件实现速度快, 且生成序列周期能达到最大的特点, 故有望代替线性反馈移位寄存器, 成为新的序列密码设计的非线性驱动环节. 然而, 虽然单圈T函数的生成序列周期能够达到最大, 但各分位序列周期仅在最高位处达到最大, 且分位越低周期越短. 为克服该弱点, 2012年游伟等人利用特殊的比特置换结合加法运算, 提出了使得各分位序列周期均达到最大的方法. 本文在此基础上, 结合单字单圈T函数的生成序列, 拓展了比特置换的设计准则, 给出了一类改进的T函数生成序列的构造方法. 分析并证明由新方法生成的序列具有良好的性质, 即每一分位序列的周期均能达到最大, 克服了T函数较低分位序列周期较小的缺陷. 进一步研究了构造方法中不同置换的个数, 输出序列的平衡性和线性复杂度, 结果表明, 该构造方法数量多, 且具有良好的平衡性及较高的线性复杂度.