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The carbon–carbon triple bond (–C≡C–) is an elementary constituent for the construction of conjugated molecular wires and carbon allotropes such as carbyne and graphyne. Here we describe a general approach to in situ synthesize –C≡C– bond on Cu(111) surface via homo-coupling of the trichloromethyl groups, enabling the fabrication of individual and arrays of poly( p -phenylene ethynylene) molecular wires. Scanning tunneling spectroscopy reveals a delocalized electronic state extending along these molecular wires, whose structure is unraveled by atomically resolved images of scanning tunneling microscopy and noncontact atomic force microscopy. Combined with density functional theory calculations, we identify the intermediates formed in the sequential dechlorination process, including surface-bound benzyl, carbene, and carbyne radicals. Our method overcomes the limitation of previous on-surface syntheses of –C≡C– incorporated systems, which require the precursors containing alkyne group; it therefore allows for a more flexible design and fabrication of molecular architectures with tailored properties. Incorporating carbon-carbon triple bonds into conjugated chains typically requires acetylenic precursors. Here, the authors synthesize poly( p -phenylene ethynylene) molecular wires on Cu(111) by directly coupling trichloromethyl-containing precursors, forming C-C triple bonds in situ

Objective This paper aims to explore the diagnostic value of enhanced magnetic resonance imaging (MRI) combined with a carcinoembryonic antigen (CEA) and carbohydrate antigen in terms of the liver metastasis of colorectal cancer. Methods A total of 167 colorectal cancer patients with liver metastasis and 167 colorectal cancer patients without liver metastasis were selected as the subjects. An automatic electrochemiluminescence analyser was then used to detect the tumour markers CEA, CA19-9, CA125 and CA72-4. The consistency between the MRI examination and clinical pathological examination was also analysed, and the sensitivity, specificity and positive and negative predictive values of various combined detection methods were compared. Results The abnormal rates of CEA, CA19-9, CA125 and CA72-4 in the two groups were statistically significant ( P < 0.05), while the results of the enhanced MRI and clinicopathological examination for liver metastasis in patients with colon cancer were largely consistent (Kappa coefficient = 0.788, P < 0.000). However, the two methods were inconsistent. The false positive rate of the enhanced MRI examination was 15.3%, while the false negative rate was 6.0%. The specificity (94.61%), positive predictive value (92.68%) and positive likelihood ratio (12.67%) were the highest for the MRI combined with serial CEA, while the sensitivity (98.80%) and negative predictive value (97.22%) were the highest with the MRI combined with parallel CEA, and this combination returned the lowest negative likelihood ratio (0.03). Conclusion The combination of MRI and CEA excludes non-metastatic patients and identifies colorectal liver metastasis cancer patients. Overall, it has a higher diagnostic value.

The aim of the study was to investigate the clinical significance of Ly-1 antibody reactive clone (LYAR) in non-small-cell lung cancer (NSCLC). The expressions of LYAR at the protein level in representative paired NSCLC tumor tissues and adjacent non-tumor tissues were measured by Western blot and immunohistochemistry. Kaplan-Meier method was used to calculate the survival curve of patients with NSCLC. Cell Counting Kit-8 assay and flow cytometry were used to estimate the cell proliferation and cell cycle, respectively. Terminal-deoxynucleotidyl-transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay was performed to detect cell apoptosis. LYAR was dramatically overexpressed in NSCLC tissues which were closely related to the survival of patients with NSCLC. In clinical studies, the expression of LYAR was related to the clinical stage, histological differentiation, and Ki-67 expression. A positive correlation was found between LYAR and Ki-67 expression by Spearman's correlation test. After serum starvation for 72 h, serum re-addition significantly increased the expression of LYAR, PCNA, and Cyclin A and promoted the cell cycle progression. LYAR knockdown inhibited the proliferation and induced the G0/G1 cell cycle arrest and apoptosis of A549 cells. The present study revealed the clinical significance of LYAR in NSCLC. LYAR might serve as a tumor promoter in NSCLC progression by promoting the proliferation and inhibiting the apoptosis of NSCLC cells. Inhibiting the expression of LYAR was considered as a potential novel therapeutic strategy for NSCLC.

Aim： To evaluate retrospectively the association of cytochrome P450 3A （CYP3A） and ATP-binding cassette sub-family B member 1 （ABCB1） gene polymorphisms with the pharmacokinetics of cyclosporine A （CsA） in Chinese renal transplant patients. Methods： One hundred and twenty-six renal transplant patients were recruited. Blood samples were collected, and corresponding clini- cal indices were recorded on the seventh day after the procedure. The patients were genotyped for CYP3A4＊IG, CYP3A5＊3C, ABCB1 1236 C〉T, ABCB1 2677 G〉T/A, and ABCB1 3435 C〉T polymorphisms. Whole blood trough concentrations of CsA at time zero （Co） were measured before the drug administration. A multiple regression model was developed to analyze the effects of genetic factors on the CsA dose-adjusted Co （Co/dose） based on several clinical indices. Results： The CYP3A5＊3C polymorphism influenced the Co and Co/dose of CsA, which were significantly higher in patients with the GG genotype than in patients with the AA or GA genotypes. No significant differences were detected for other SNPs （CYP3A4＊IG, ABCB1 1236 C〉T, ABCB1 2677 G〉T/A, and ABCB1 3435 C〉T）. In a univariate analysis using Pearson＇s correlation test, age, hemoglobin, blood urea nitrogen and blood creatinine levels were significantly correlated with the log-transformed CsA Co/dose. In the multiple regression model, CYP3A5＊3C, age, hemoglobin and blood creatinine level were associated with the log-transformed CsA Co/dose. Conclusion： CYP3A5＊3C correlates with the Co/dose of CsA on the seventh day after renal transplantation. The allele is a putative indi- cator for the optimal CsA dosage in the early phase of renal transplantation in the Chinese population.

Because of a lack of sensitive biomarkers,the diagnosis of Alzheimer＇s disease（AD） cannot be made prior to symptom manifestation.Therefore,it is crucial to identify novel biomarkers for the presymptomatic diagnosis of AD.While brain lesions are a major feature of AD,retinal pathological changes also occur in patients.In this study,we investigated the temporal changes in β-site APP-cleaving enzyme 1（BACE1） expression in the retina and brain to determine whether it could serve as a suitable biomarker for early monitoring of AD.APP/PS-1 transgenic mice,3,6 and 8 months of age,were used as an experimental group,and age-matched C57/BL6 wild-type mice served as the control group.In the Morris water maze test,there were no significant differences in escape latency or in the number of crossings in the target area among mice of different ages.Compared with wild-type mice,no changes in learning or memory abilities were detected in transgenic mice at 3 months of age.However,compared with wild-type mice,the escape latency was significantly increased in transgenic mice at 6 months,starting on day 3,and at 8 months,starting on day 2,during Morris water maze training.In addition,the number of crossings of the target area was significantly decreased in transgenic mice.The learning and memory abilities of transgenic mice were further worsened at 8 months of age.Immunohistochemical staining revealed no BACE1 plaques in wild-type mice at 3,6 or 8 months or in transgenic mice at 3 months,but they were clearly found in the entorhinal cortex,hippocampus and prefrontal cortex of transgenic mice at 6 and 8 months.BACE1 expression was not detected in the retina of wild-type mice at 3 months,but weak BACE1 expression was detected in the ganglion cell layer,inner plexiform layer and outer plexiform layer at 6 and 8 months.In transgenic mice,BACE1 expression in the ganglion cell layer was increased at 3 months,and BACE1 expression in the ganglion cell layer,inner plexiform layer and outer plexiform layer was significantly increased at 6 and 8 months,compared with age-matched wild-type mice.Taken together,these results indicate that changes in BACE1 expression appear earlier in the retina than in the brain and precede behavioral deficits.Our findings suggest that abnormal expression of BACE1 in the retina is an early pathological change in APP/PS-1 transgenic mice,and that BACE1 might have potential as a biomarker for the early diagnosis of AD in humans.

Aim： To characterize the pharmacological profiles of a novel K-opioid receptor agonist MB-1C-OH. Methods： [3H]diprenorphine binding and [35S]GTPyS binding assays were performed to determine the agonistic properties of MB-lC-OH Hot plate, tail flick, acetic acid-induced writhing, and formalin tests were conducted in mice to evaluate the antinociceptive actions. Forced swimming and rotarod tests of mice were used to assess the sedation and depression actions. Results： In [3H]diprenorphine binding assay, MB-lC-OH did not bind to p- and 6-opioid receptors at the concentration of 100 μmol/L, but showed a high affinity for κ-opioid receptor （K1=35 nmol/L）. In [35S]GTPγS binding assay, the compound had an Emax of 98% and an ECso of 16.7 nmol/L for κ-opioid receptor. Subcutaneous injection of MB-lC-OH had no effects in both hot plate and tail flick tests, but produced potent antinociception in the acetic acid-induced writhing test （ED50=0.39 mg/kg）, which was antagonized by pretreatment with a selective κ-opioid receptor antagonist Nor-BNI. In the formalin test, subcutaneous injection of MB-lC-OH did not affect the flinching behavior in the first phase, but significantly inhibited that in the second phase （ED50=0.87 mg/kg）. In addition, the sedation or depression actions of MB-lC-OH were about 3-fold weaker than those of the classical K agonist （-）U50,488H. Conclusion： MB-1C-OH is a novel K-opioid receptor agonist that produces potent antinociception causing less sedation and depression.

Treatment of intervertebral disc degeneration (IDD) seeks to prevent senescence and death of nucleus pulposus (NP) cells. Previous studies have shown that sirt6 exerts potent anti-senescent and anti-apoptotic effects in models of age-related degenerative disease. However, it is not known whether sirt6 protects against IDD. Here, we explored whether sirt6 influenced IDD. The sirt6 level was reduced in senescent human NP cells. Sirt6 overexpression protected against apoptosis and both replicative and stress-induced premature senescence. Sirt6 also activated NP cell autophagy both in vivo and in vitro. 3-methyladenine (3-MA) and chloroquine (CQ)-mediated inhibition of autophagy partially reversed the anti-senescent and anti-apoptotic effects of sirt6, which regulated the expression of degeneration-associated proteins. In vivo, sirt6 overexpression attenuated IDD. Together, the data showed that sirt6 attenuated cell senescence, and reduced apoptosis, by triggering autophagy that ultimately ameliorated IDD. Thus, sirt6 may be a novel therapeutic target for IDD treatment.

This paper develops an economic evaluation framework for pumped storage hydropower (PSH) projects based on real options, addressing the limitations of traditional economic evaluation methods that neglect investment flexibility and path dependence. The framework integrates an annual net cash flow model with an improved mean-reverting electricity price model to generate thousands of electricity price trajectories, while backward dynamic programming dynamically values abandonment options. The core innovation of this study lies in the dynamic pricing mechanism of abandonment options, which explicitly captures the flexibility of terminating projects under adverse conditions. A comparative analysis between the traditional NPV approach and the real options method reveals significant differences: the average NPV under base scenario is −38.35 million CNY, whereas option scenario yields an average NPV of 143.15 million CNY. The average value of real options is 181.5 million yuan, and it increases the average internal rate of return by 0.34%. These results demonstrate that incorporating real options prevents the underestimation of project value and provides more robust decision-making support under uncertainty, thereby offering methodological and policy insights for the investment appraisal of large-scale energy storage projects.

Activation of complement system in central nervous system (CNS) of the patients suffering from prion diseases or animal models infected with prion agents experimentally is reported repeatedly, but which pathways are involved in the complement system during prion infection is not well documented. Here, we evaluated the level of complement factor B (CFB), which is the key factor that triggers alterative pathway (AP) of complement in the brain tissues of scrapie-infected mice with various methodologies. We found that the levels of mRNA and protein of CFB significantly increased in the brain tissues of scrapie-infected mice. Morphologically, the increased CFB-specific signal overlapped with the elevated C3 signal in brain sections of scrapie-infected mice, meanwhile overlapped with damaged neurons and activated microglia, but not with the proliferative astrocytes. Additionally, the level of complement factor P (CFP), the key positive regulator of AP, also increased remarkably in the brain tissues of infected mice. The transcriptional levels of CD55 and CD46, two negative regulators of AP, decreased without significance in brain tissues of scrapie-infected mice at the terminal stage. However, the mRNA and protein levels of CFH, another negative regulator of AP, increased. Through the dynamic analyses of the expressions of CFB, CFP, and CFH in brain sections of 139A-infected mice, which were collected at different time-points during incubation period, illustrated time-dependent increase levels of each factor during the incubation period of scrapie infection. Taken together, our data here demonstrate that the AP of complement cascade is activated in the CNS microenvironment during prion infection.