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Objective: The present study investigated the predictive diseases progression value of preoperative fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with local advanced cervical cancer (LACC). Methods: In total, 267 patients [median age 58 (range: 27–85) years old] with LACC underwent 18F-FDG PET/CT prior to any treatment. The maximum standardized uptake values (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary lesion and metastatic lymph nodes were measured on PET/CT and correlated with clinicopathological features and progression-free survival (PFS). Results: The median follow-up was 36.52 (range: 3.09–61.29) months. During the observation period, 80 (30.0%) patients exhibited disease progression. Univariate analysis showed that FIGO stage, concurrent chemoradiotherapy (CRT), serum level of carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC-Ag), primary tumor MTV (pMTV) and TLG (pTLG), lymph nodes SUVmax (nSUVmax) and TLG (nTLG), and total metabolic activity (sMTV, sTLG) were associated with PFS. nSUVmax ≥ 5.29, CEA ≥ 7.11 ng/ml and deficiency of concurrent CRT were independent risk factor for PFS (p = 0.006, p = 0.008, p = 0.014). The 3-year PFS for patients with high nSUVmax were 42.2% compared to 56.3% for low nSUVmax values. Conclusion: Pretreatment cervical and lymph nodes metabolic parameters were associated with PFS in patients with LACC. [ABSTRACT FROM AUTHOR]

As an advanced amorphous material, sp3 amorphous carbon exhibits exceptional mechanical, thermal and optical properties, but it cannot be synthesized by using traditional processes such as fast cooling liquid carbon and an efficient strategy to tune its structure and properties is thus lacking. Here we show that the structures and physical properties of sp3 amorphous carbon can be modified by changing the concentration of carbon pentagons and hexagons in the fullerene precursor from the topological transition point of view. A highly transparent, nearly pure sp3−hybridized bulk amorphous carbon, which inherits more hexagonal-diamond structural feature, was synthesized from C70 at high pressure and high temperature. This amorphous carbon shows more hexagonal-diamond-like clusters, stronger short/medium-range structural order, and significantly enhanced thermal conductivity (36.3 ± 2.2 W m−1 K−1) and higher hardness (109.8 ± 5.6 GPa) compared to that synthesized from C60. Our work thus provides a valid strategy to modify the microstructure of amorphous solids for desirable properties. sp3 amorphous carbon exhibits exceptional mechanical, thermal, and optical properties, but cannot be synthesized using traditional processes. Here authors report a nearly pure sp3−hybridized amorphous carbon synthesized from C70 which shows more short/medium-range order and enhanced thermal conductivity compared to C60. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy targeting PD-1/PD-L1 has been proven to be effective for cervical cancer treatment. To explore non-invasive examinations for assessing the PD-L1 status in cervical cancer, we performed a retrospective study to investigate the predictive value of 18F-FDG PET/CT. Methods: The correlations between PD-L1 expression, clinicopathological characteristics and 18F-FDG PET/CT metabolic parameters were evaluated in 74 cervical cancer patients. The clinicopathological characteristics included age, histologic type, tumor differentiation, FIGO stage and tumor size. The metabolic parameters included maximum standard uptake (SUVmax), mean standard uptake (SUVmean), total lesion glycolysis (TLG) and tumor metabolic volume (MTV). Results: In univariate analysis, SUVmax, SUVmean, TLG, tumor size and tumor differentiation were obviously associated with PD-L1 status. SUVmax (rs = 0.42) and SUVmean (rs = 0.40) were moderately positively correlated with the combined positive score (CPS) for PD-L1 in Spearman correlation analysis. The results of multivariable analysis showed that the higher SUVmax (odds ratio = 2.849) and the lower degree of differentiation (Odds Ratio = 0.168), the greater probability of being PD-L1 positive. The ROC curve analysis demonstrated that when the cut-off values of SUVmax, SUVmean and TLG were 10.45, 6.75 and 143.4, respectively, the highest accuracy for predicting PD-L1 expression was 77.0%, 71.6% and 62.2%, respectively. The comprehensive predictive ability of PD-L1 expression, assessed by combining SUVmax with tumor differentiation, showed that the PD-L1-negative rate was 100% in the low probability group, whereas the PD-L1-positive rate was 84.6% in the high probability group. In addition, we also found that the H-score of HIF-1α was moderately positively correlated with PD-L1 CPS (rs = 0.51). Conclusions: The SUVmax and differentiation of the primary lesion were the optimum predictors for PD-L1 expression in cervical cancer. There was a great potential for 18F-FDG PET/CT in predicting PD-L1 status and selecting cervical cancer candidates for PD1/PD-L1 immune checkpoint therapy. [ABSTRACT FROM AUTHOR]

Objective. This study investigated whether lncRNA NEAT1 could inhibit the proliferation of cutaneous squamous cell carcinoma (CSCC) cells by targeting miR-342-3p/CUL4B, thereby affecting the occurrence and development of CSCC. Methods. Fluorescence quantitative PCR was used to detect the expression of lncRNA NEAT1 and miR-42-3p in skin squamous cell carcinoma and adjacent tissues. Bioinformatics software and luciferase reporter gene assay were used to analyze the association of lncRNA NEAT1 and miR-342-3p. The effect of overexpression or knockdown of miR-342-3p on the proliferation of CSCC cells was examined by MTT and colony formation assays. Western blotting was used to detect the proteins of the miR-342-3p/CUL4B signaling axis. Results. The lncRNA NEAT1 is abnormally overexpressed in CSCC tissues and cell lines. The expression of lncRNA NEAT1 and miR-342-3p in CSCC was negatively correlated. Bioinformatics prediction analysis revealed that lncRNA NEAT1 regulates the expression of miR-342-3p. The results of MTT and plate colony formation experiments showed that the transfection of miR-342-3p mimics significantly inhibited the proliferation and plate colony formation of CSCC cells, while the transfection of miR-342-3p inhibitor significantly promoted the proliferation and plate colony-forming ability of CSCC cells. Western blot results showed that lncRNA NEAT1 affected CSCC cell proliferation through miR-342-3p/CUL4B/PI3K-Akt signaling pathway. Conclusion. The expression of lncRNA NEAT1 and miR-342-3p in CSCC tissues was negatively correlated. This study is the first to demonstrate that the lncRNA NEAT1, as a ceRNA, affects the proliferation of skin squamous cell carcinoma cells through the miR-342-3p/CUL4B/PI3K-Akt signaling pathway. Therefore, lncRNA NEAT1 could be a biological marker or target for CSCC diagnosis or treatment. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the aggressive behavior of triple-negative breast cancer (TNBC) cells that had survived ionizing radiation and explore the potential targets of TNBC combination treatment. Consistent with the previous literature, Axl was highly expressed in TNBC and closely associated with the degree of malignancy based on immunohistochemical staining. Using a gradient irradiation method, the ionizing radiation-resistant mouse TNBC cell line 4T-1/IRR was established. It was found that Axl expression was upregulated in 4T-1/IRR cells. After irradiation by X-ray, the cell viability and colony formation ability of 4T-1/IRR cells were significantly increased when compared with the 4T-1 cells. Combined radiotherapy with Axl inhibition by treatment with R428 and small interfering RNA lentivirus targeting Axl infection significantly reduced cell viability, colony formation ability, DNA double-stranded break repair, and the invasive and migratory ability of 4T-1/IRR cells. In vivo, the small animal radiation research platform was applied to precisely administer radiotherapy of the tumor-bearing mice. R428 treatment combined with 6 Gy X-ray significantly inhibited the growth of 4T-1/IRR cells-derived xenograft tumors in the BALB/c mouse. The results of western blotting showed that the critical molecular mechanism involved in the radioresistance of TNBC cells was the PI3K/Akt/mTOR signaling pathway induced by Axl activation. Thus, it is hypothesized that targeted Axl therapy combined with radiotherapy may have significant potential for the treatment of TNBC. [ABSTRACT FROM AUTHOR]

Abstract: Renal‐clearable nanoparticles have made it possible to overcome the toxicity by nonspecific accumulation in healthy tissues/organs due to their highly efficient clearance characteristics. However, their tumor uptake is relatively low due to the short blood circulation time and rapid body elimination. Here, this problem is addressed by developing renal‐clearable nanoparticles by controlled coating of sub‐6 nm CuS nanodots (CuSNDs) on doxorubicin ladened mesoporous silica nanoparticles (pore size ≈6 nm) for multimodal application. High tumor uptake of the as‐synthesized nanoparticles (abbreviated as MDNs) is achieved due to the longer blood circulation time. The MDNs also show excellent performance in bimodal imaging. Moreover, the MDNs demonstrated a photothermally sensitive drug release and pronounced synergetic effects of chemo‐photothermal therapy, which were confirmed by two different tumor models in vivo. A novel key feature of the proposed synthesis is the use of renal‐clearable CuSNDs and biodegradable mesoporous silica nanoparticles which also are renal‐clearable after degradation. Therefore, the MDNs would be rapidly degraded and excreted in a reasonable period in living body and avoid long‐term toxicity. Such biodegradable and clearable single‐compartment theranostic agents applicable in highly integrated multimodal imaging and multiple therapeutic functions may have substantial potentials in clinical practice. [ABSTRACT FROM AUTHOR]

Low temperature thermo-luminescence (TL) has been applied to measurements of the ionization energy of donors in ZnO. Three hydrogen-related donors were characterized with ionization energies of 36, 47, and 55 meV--values that are in complete agreement with previous reports. The donor types can be "switched" by relevant thermal treatments. This work shows that TL can be used to measure the donor energies in luminescent semiconductors in general. This approach can be particularly useful for thin-film investigations when the results of Hall-effect measurements are obscured by contributions from conductive interfaces or substrates. [ABSTRACT FROM AUTHOR]

Abstract: In terms of energy resolution, temporal response to burst events, and thermal stability, lanthanum bromide doped with Ce is a much better choice than the traditional NaI(Tl) scintillator for hard X-ray astronomy. We present the test results of a phoswich detector with a diameter of 101.6mm consisting of 6mm thick LaBr3:Ce and 40mm thick NaI(Tl), which is the largest one of this type reported so far. The measured energy resolution is 10.6% at 60keV, varying inversely proportional to the square root of the energy, and the energy nonlinearity is found to be less than 1%, as good as those of smaller phoswiches. The coupled scintillators and phototube also show excellent uniformity across the detecting surface, with a deviation of 0.7% on the pulse amplitude produced by 60keV gamma-rays. Thanks to the large ratio of light decay times of NaI(Tl) and LaBr3:Ce, 250ns versus 16ns, pulse shape discrimination is much easier for this combination than for NaI(Tl)/CsI(Na). As the light decay time of LaBr3:Ce is about 15 times faster than that of NaI(Tl), this phoswich is more suitable for detection of bright, transient sources such as gamma-ray bursts and soft gamma-ray repeaters. The internal activity of lanthanum produces a count rate of about 6countss−1 at 37.5keV in the detector. This peak could be used for in-flight spectral calibration and gain correction. [Copyright &y& Elsevier]

For improving dispersion of carbon nanotubes (CNTs) in a polymer matrix, multiwalled carbon nanotubes (MWCNTs) were first modified by ring-opening polymerization of the terminal hydroxyl of MWCNTs with ε-caprolactone (ε-CL). Then, the modified MWCNTs were added into polyurethane (PU) and MWCNTs/PU For improving dispersion of carbon nanotubes (CNTs) in a polymer matrix, multiwalled carbon nanotubes (MWCNTs) were first modified by ring-opening polymerization of the terminal hydroxyl of MWCNTs with ε-caprolactone (ε-CL). Then, the modified MWCNTs were added into polyurethane (PU) and MWCNTs/PU composite fibers were prepared by electrospinning and collected in the form of membranes. The morphology and microstructure of the composite nanofibers were analyzed by SEM. The relationship between the tensile properties of the membranes and the mass fraction of the MWNTs was revealed by tensile testing. [ABSTRACT FROM AUTHOR]

Background: It has been long recognized that cranial irradiation used for the treatment of primary and metastatic brain tumor often causes neurological side-effects such as intellectual impairment, memory loss and dementia, especially in children patients. Our previous study has demonstrated that whole-brain irradiation (WBI) can cause cognitive decline in rats. Minocycline is an antibiotic that has shown neuroprotective properties in a variety of experimental models of neurological diseases. However, whether minocycline can ameliorate cognitive impairment induced by ionizing radiation (IR) has not been tested. Thus this study aimed to demonstrate the potential implication of minocycline in the treatment of WBI-induced cognitive deficits by using a rat model. Methods: Sprague Dawley rats were cranial irradiated with electron beams delivered by a linear accelerator with a single dose of 20 Gy. Minocycline was administered via oral gavages directly into the stomach before and after irradiation. The open field test was used to assess the anxiety level of rats. The Morris water maze (MWM) was used to assess the spatial learning and memory of rats. The level of apoptosis in hippocampal neurons was measured using immunohistochemistry for caspase-3 and relative markers for mature neurons (NeuN) or for newborn neurons (Doublecortin (DCX)). Neurogenesis was determined by BrdU incorporation method. Results: Neither WBI nor minocycline affected the locomotor activity and anxiety level of rats. However, compared with the sham-irradiated controls, WBI caused a significant loss of learning and memory manifest as longer latency to reach the hidden platform in the MWM task. Minocycline intervention significantly improved the memory retention of irradiated rats. Although minocycline did not rescue neurogenesis deficit caused by WBI 2 months post-IR, it did significantly decreased WBI-induced apoptosis in the DCX positive neurons, thereby resulting in less newborn neuron depletion 12 h after irradiation. Conclusions: Minocycline significantly inhibits WBI-induced neuron apoptosis, leading to less newborn neurons loss shortly after irradiation. In the long run, minocycline improves the cognitive performance of rats post WBI. The results indicate a potential clinical implication of minocycline as an effective adjunct in radiotherapy for brain tumor patients.

Well-developed bipolar resistive switching behaviors have been revealed in Pt/GaOx/ITO stacks without an electroforming process. By substituting platinum with titanium as the top electrode, switching polarity changed from 'counter-Figure-8' to 'Figure-8.' The modulation of Schottky barrier at the Pt/GaOx interface induced by migration of oxygen vacancies was proposed to explain the switching in Pt/GaOx/ITO stacks, while the switching in Ti/GaOx/ITO stacks was ascribed to the redox reaction at the Ti/GaOx interface. Our experimental result further confirms the migration of oxygen vacancies in the vicinity of the electrode area plays an important role in the resistive switching process. [ABSTRACT FROM AUTHOR]

A new x-ray luminescence based spectrometer was developed and installed to examine the scintillation properties of materials while revealing the origins of luminescence and investigating trapping defects. Measurements were performed on a number of undoped and Ce doped yttrium aluminum garnet crystals and various luminescence centers were characterized. The measured x-ray luminescence spectra provide information about the spectral range and the scintillation efficiency and linearity. The efficiency of charge-carriers production due to x ray, their energy transfer to the luminescence centers, and the efficiency of luminescence are all reflected in the efficiency of x-ray luminescence. [ABSTRACT FROM AUTHOR]

The phosphorus (P) fractions and bioavailable P in the sediments from the Quanzhou Bay Estuarine Wetland Nature Reserve were investigated using chemical extraction methods for the first time to study the distribution and bioavailability of P in the reserve sediments. A hypothesis was presented suggesting that the bioavailable P in the sediments could be evaluated using the P fractions. The total phosphorus (TP), inorganic phosphorus (IP), organic phosphorus (OP), non-apatite phosphorus (NAIP), and apatite phosphorus (AP) contents in the sediments were in the ranges of 303.87–761.59 mg kg −1 , 201.22–577.66 mg kg −1 , 75.83–179.16 mg kg −1 , 28.86–277.90 mg kg −1 , and 127.36–289.94 mg kg −1 , respectively. The water soluble phosphorus (WSP), readily desorbable phosphorus (RDP), algal available phosphorus (AAP), and NaHCO 3 extractable phosphorus (Olsen-P) contents in the sediments were in the ranges of 0.58–357.17 mg kg −1 , 80.77–586.75 mg kg −1 , 1.09–24.12 mg kg −1 , and 54.96–676.82 mg kg −1 , respectively. The correlation analysis results showed that the NAIP was the major component of the bioavailable P and that the impact of the AP on the bioavailable phosphorus may be minimal. Due to the low TP content in the sediments of the Quanzhou Bay Estuarine Wetland Nature Reserve, the potential pollution risks of P in the sediments may not be very high. The results also show that the bioavailable P concentrations in the sediments of the Quanzhou Bay Estuarine Wetland Nature Reserve could not be evaluated by measuring the P fractions and that the hypothesis was untenable. [ABSTRACT FROM AUTHOR]

The present study compared the ecosystem organic carbon (OC) stocks and soil OC sources between two 12-year-old monospecific mangrove sites comprised of different species (Kandelia obovata in tree form and Aegiceras corniculatum in shrub form). We tested whether the carbon sequestration performance following rehabilitation varied with plantation of species in different forms and whether mangrove vegetation sequestrate OC more rapidly than soil pool. The results showed that mangrove rehabilitation increased the ecosystem OC stock relative to that of a non-vegetated bare flat. The accumulation of soil carbon was accompanied by increased soil total nitrogen contents and decreased δ13C values of soil OC, indicating that the increases in OC and TN contents were a function of accumulation of 13C-depleted mangrove materials in the soil. The sequestrated OC over the 12 years was considerably less in soil than in biomass at each mangrove site, suggesting that mangrove vegetation contributes more rapidly than the soil to ecosystem OC sequestration following rehabilitation before the vegetation has reached maturity. Compilation of the carbon stocks from worldwide rehabilitated mangrove forests with various ages further supports this finding. The K. obovata site had an apparently higher biomass OC stock but less OC in the soil than those at the A. corniculatum site. There was a higher standing leaf litter stock on the forest floor and more mangrove materials incorporated into the top 15 cm soil at the A. corniculatum site. These results suggested that the two rehabilitated mangrove sites had different development trajectories of both biomass and soil OC sequestration. Moreover, the performance of ecosystem carbon sequestration was related to plantation of different mangrove species. These carbon sequestration feature of rehabilitated mangrove forests therefore deserve attention in future rehabilitation programs to promote carbon sequestration performance. Unlabelled Image • We compared ecosystem OC stocks between planted mangroves comprised of different species. • Vegetations sequestrate OC more rapidly than soils before they have reached maturity. • Ecosystem OC sequestration performance is related to plantation of different species. • Shrubby mangroves favor the incorporation of mangrove materials into soils. [ABSTRACT FROM AUTHOR]

At present, the reconfiguration, maintenance, and review of power lines play a pivotal role in maintaining the stability of electrical grid operations and ensuring the accuracy of electrical energy measurements. These essential tasks not only guarantee the uninterrupted functioning of the power system, thereby improving the reliability of the electricity supply but also facilitate precise electricity consumption measurement. In view of these considerations, this article endeavors to address the challenges posed by power line restructuring, maintenance, and inspections on the stability of power grid operations and the accuracy of energy metering. To accomplish this goal, this article introduces an enhanced methodology based on the hidden Markov model (HMM) for identifying the topology of distribution substations. This approach involves a thorough analysis of the characteristic topology structures found in low-voltage distribution network (LVDN) substations. A topology identification model is also developed for LVDN substations by leveraging time series data of electricity consumption measurements and adhering to the principles of energy conservation. The HMM is employed to streamline the dimensionality of the electricity consumption data matrix, thereby transforming the topology identification challenge of LVDN substations into a solvable convex optimization problem. Experimental results substantiate the effectiveness of the proposed model, with convergence to minimal error achieved after a mere 50 iterations for long time series data. Notably, the method attains an impressive discriminative accuracy of 0.9 while incurring only a modest increase in computational time, requiring a mere 35.1 milliseconds. By comparison, the full-day data analysis method exhibits the shortest computational time at 16.1 milliseconds but falls short of achieving the desired accuracy level of 0.9. Meanwhile, the sliding time window analysis method achieves the highest accuracy of 0.95 but at the cost of a 50-fold increase in computational time compared to the proposed method. Furthermore, the algorithm reported here excels in terms of energy efficiency (0.89) and load balancing (0.85). In summary, the proposed methodology outperforms alternative approaches across a spectrum of performance metrics. This article delivers valuable insights to the industry by fortifying the stability of power grid operations and elevating the precision of energy metering. The proposed approach serves as an effective solution to the challenges entailed by power line restructuring, maintenance, and inspections., Competing Interests: Jianfeng Ji is employed by Beijing Zhixiang Technology Co., Ltd and Yongjin Xu, Jifan Lv, Jiaying Wang, Fangbin Ye and Shen Ye are employed by the State grid Zhejiang marketing service center. The authors declare that they have no competing interests., (© 2024 Xu et al.)

In light of the aging demographic in China, heightened attention is warranted for the mental well-being of elderly individuals. Nevertheless, the prevalence of suicidal ideation among older residents in Chinese nursing homes and the nuanced impact of family support on this phenomenon, mediated by anxiety and depressive symptoms, remain unclear. A cohort of 506 Chinese elderly adults participated in the study. Psychosocial traits were assessed using the Perceived Social Support from Family scale (PSS-Fa) for family support, the 7-item Generalized Anxiety Disorder scale (GAD-7) for anxiety symptoms, the 9-item Patient Health Questionnaire (PHQ-9) for depressive symptoms, and suicidal ideation. A structural equation model (SEM) was employed to execute a serial mediation model. The analysis of 506 elderly adults revealed that 8.1% reported varying levels of suicidal ideation within Chinese nursing homes. The pathway from family support to anxiety symptoms (standardized beta = -0.025, P = .241), family support to depressive symptoms (standardized beta = -0.072, P < .05), and family support to suicidal ideation (standardized beta = -0.082, P < .05) were explored. Additionally, pathways from anxiety symptoms to suicidal ideation (standardized beta = 0.364, P < .001), anxiety symptoms to depressive symptoms (standardized beta = 0.647, P < .001), and depressive symptoms to suicidal ideation (standardized beta = 0.369, P < .001) were examined. This study elucidated the underlying mechanisms connecting family support to suicidal ideation, with depressive symptoms partially mediating this association. Additionally, our discoveries shed light on the partial mediation of anxiety symptoms by depressive factors when it came to the realm of suicidal ideation., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Hypoxia is an important tumor feature and hypoxia-inducible factor 1 (HIF-1) is a master regulator of cell response to hypoxia. Mouse double minute 2 homolog (MDM2) promotes cancer cell survival in retinoblastoma (RB), with the underlying mechanism remaining elusive. In this study, we investigated the role of MDM2 and its relation to HIF-1α in RB. Expression analysis on primary human RB samples showed that MDM2 expression was positively correlated with that of HIF-1α while negatively correlated with von Hippel-Lindau protein (pVHL), the regulator of HIF-1α. In agreement, RB cells with MDM2 overexpression showed increased expression of HIF-1α and decreased expression of pVHL, while cells with MDM2 siRNA knockdown or MDM2-specific inhibitor showed the opposite effect under hypoxia. Further immuno-precipitation analysis revealed that MDM2 could directly interact with pVHL and promotes its ubiquitination and degradation, which consequently led to the increase of HIF-1α. Inhibition of MDM2 and/or HIF-1α with specific inhibitors induced RB cell death and decreased the stem cell properties of primary RB cells. Taken together, our study has shown that MDM2 promotes RB survival through regulating the expression of pVHL and HIF-1α, and targeting MDM2 and/or HIF-1α represents a potential effective approach for RB treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Xu, Li, Ji, Jin, Chen, Gan, Tao and Chai.)

Fibroblast growth factor receptor 4 (FGFR4) has been identified as a potential target due to its transmission of the FGF19 signaling pathway, which is critical to hepatocellular carcinoma (HCC). Therefore, focusing on the specific Cys552 of FGFR4 subtype, we designed and synthesized a novel family of 1,6-naphthyridin-2(1 H )-one derivatives as potent and highly selective FGFR4 inhibitors. Through detailed structural optimizations, the representative compound A34 exhibited improved FGFR4 inhibitory capability and selectivity and excellent anti-proliferative activities against FGFR4-dependent HCC cell lines. Additionally, A34 demonstrated remarkable antitumor efficacy in a Hep-3B HCC xenograft model, with favorable pharmacokinetic properties, and low risk of hERG toxicity. A34 also showed moderate inhibitory activities against the FGFR4 V550L mutant in vitro, which indicates that it has the potential as a novel anticancer agent for HCC.

Background: The incidence of cutaneous squamous cell carcinoma (CSCC), a malignant tumor that threatens human life, is increasing every year, and yet its pathogenesis is still unclear. This study found that long noncoding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) was abnormally expressed in CSCC. However, the biochemical mechanisms of lncRNA NEAT1 in carcinogenesis and the development of cancer remain unclear., Methods: Fluorescence quantitative polymerase chain reaction (qPCR) was conducted to determine lncRNA NEAT1 expression in CSCC and paracarcinoma tissues and investigate the correlation between NEAT1 levels and patients' clinicopathological features. The invasion, proliferation, and migration of CSCC cells were measured using colony formation, Cell Counting Kit-8, and Transwell assays. Western blot assay was conducted to test whether NEAT1 knockdown affected invasion and migration-related proteins. In addition, a nude mouse subcutaneous tumorigenesis experiment was performed to determine whether the knockdown of NEAT1 affected the proliferation ability of CSCC cells., Results: Changes in lncRNA NEAT1 expression in CSCC tissues were correlated with the degree of lymph node metastasis and the tumor, regional lymph nodes, and distant metastasis (TNM) grade of patients. The downregulation of NEAT1 lncRNA significantly impeded cell invasion, proliferation, and migration in CSCC. Through lncRNA NEAT1 knockdown, significant reductions in metalloproteinase-2, metalloproteinase-9, N-cadherin, and vimentin expression were observed, and the level of E-cadherin increased. In vivo experiments in nude mice revealed that knockdown of lncRNA NEAT1 greatly inhibited cell proliferation in CSCC., Conclusions: In CSCC tissues, NEAT1 lncRNA was expressed at high levels and correlated with lymph node metastasis and TNM stage. The knockdown of NEAT1 lncRNA could significantly impede CSCC proliferation, metastasis, and invasion. Additionally, by measuring the expression level of lncRNA NEAT1, we may be able to detect the clinical and pathological characteristics of CSCC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-21-6916/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

A landmark study from the Institute of Medicine reported that the assessment of cognitive difficulties in children with epilepsy is timely and imperative. Anticonvulsant-induced cognitive impairment could influence the quality of life more than seizure itself in patients. Although the monoaminergic system is involved in the regulation of cognitive process, its role in anticonvulsant-induced cognitive impairment remains unclear. Methods: To explore in vivo monoamine receptor binding activity in patients with anticonvulsant-induced cognitive impairment, each patient underwent PET imaging with both monoamine receptor binding agent 11 C- N -methylspiperone and glucose metabolic agent 18 F-FDG. Tests of intelligence quotient (IQ), including verbal IQ (VIQ), performance IQ (PIQ), and full-scale IQ (FSIQ), were performed in each patient. Results: Compared with the patients with monotherapy, patients with polytherapy had significantly lower VIQ, PIQ, and FSIQ ( P < 0.01 in each comparison), as well as significantly lower monoamine receptor activities detected in the caudate nucleus, prefrontal cortex, dorsal anterior cingulate cortex, and amygdale ( P < 0.05 in each comparison). However, regarding the glucose metabolism, there was no significant difference found in patients with monotherapy or polytherapy ( P > 0.05). Conclusion: Monoamine receptor PET imaging could be a promising in vivo imaging biomarker for mapping anticonvulsant-induced cognitive impairment., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

PET with 18 F-FDG has been used for presurgical localization of epileptogenic foci; however, in nonsurgical patients, the correlation between cerebral glucose metabolism and clinical severity has not been fully understood. The aim of this study was to evaluate the glucose metabolic profile using 18 F-FDG PET/CT imaging in patients with epilepsy. Methods: One hundred pediatric epilepsy patients who underwent 18 F-FDG PET/CT, MRI, and electroencephalography examinations were included. Fifteen age-matched controls were also included. 18 F-FDG PET images were analyzed by visual assessment combined with statistical parametric mapping (SPM) analysis. The absolute asymmetry index (|AI|) was calculated in patients with regional abnormal glucose metabolism. Results: Visual assessment combined with SPM analysis of 18 F-FDG PET images detected more patients with abnormal glucose metabolism than visual assessment only. The |AI| significantly positively correlated with seizure frequency ( P < 0.01) but negatively correlated with the time since last seizure ( P < 0.01) in patients with abnormal glucose metabolism. The only significant contributing variable to the |AI| was the time since last seizure, in patients both with hypometabolism ( P = 0.001) and with hypermetabolism ( P = 0.005). For patients with either hypometabolism ( P < 0.01) or hypermetabolism ( P = 0.209), higher |AI| values were found in those with drug resistance than with seizure remission. In the post-1-y follow-up PET studies, a significant change of |AI| (%) was found in patients with clinical improvement compared with those with persistence or progression ( P < 0.01). Conclusion: 18 F-FDG PET imaging with visual assessment combined with SPM analysis could provide cerebral glucose metabolic profiles in nonsurgical epilepsy patients. |AI| might be used for evaluation of clinical severity and progress in these patients. Patients with a prolonged period of seizure freedom may have more subtle (or no) metabolic abnormalities on PET. The clinical value of PET might be enhanced by timing the scan closer to clinical seizures., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Unlabelled: Brain-computer interface (BCI) technology has great potential for improving the quality of life for neurologic patients. This study aimed to use PET mapping for BCI-based stimulation in a rat model with electrodes implanted in the ventroposterior medial (VPM) nucleus of the thalamus., Methods: PET imaging studies were conducted before and after stimulation of the right VPM., Results: Stimulation induced significant orienting performance. (18)F-FDG uptake increased significantly in the paraventricular thalamic nucleus, septohippocampal nucleus, olfactory bulb, left crus II of the ansiform lobule of the cerebellum, and bilaterally in the lateral septum, amygdala, piriform cortex, endopiriform nucleus, and insular cortex, but it decreased in the right secondary visual cortex, right simple lobule of the cerebellum, and bilaterally in the somatosensory cortex., Conclusion: This study demonstrated that PET mapping after VPM stimulation can identify specific brain regions associated with orienting performance. PET molecular imaging may be an important approach for BCI-based research and its clinical applications., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Radiotherapy is an important procedure for the treatment of inoperable non-small cell lung cancer (NSCLC). However, recent evidence has shown that irradiation can promote the invasion and metastasis of several types of cancer, and the underlying mechanisms are not fully understood. This study aimed to investigate the molecular mechanism by which radiation enhances the invasiveness of NSCLC cells. We found that after irradiation, hypoxia-inducible factor 1α (HIF-1α) was increased and translocated into the nucleus, where it bound to the hypoxia response element (HRE) in the CXCR4 promoter and promoted the transcription of CXCR4. Furthermore, reactive oxygen species (ROS) also plays a role in the radiation-induced expression of CXCR4. Our results revealed that 2 Gy X-ray irradiation promoted the metastasis and invasiveness of H1299, A549 and H460 cells, which were significantly enhanced by SDF-1α treatment. Blocking the SDF-1α/CXCR4 interaction could suppress the radiation-induced invasiveness of NSCLC cells. The PI3K/pAkt and MAPK/pERK1/2 pathways were found to be involved in radiation-induced matrix metalloproteinase (MMP) expression. In vivo, irradiation promoted the colonization of H1299 cells in the liver and lung, which was mediated by CXCR4. Altogether, our findings have elucidated the underlying mechanisms of the irradiation-enhanced invasiveness of NSCLC cells.

Radiotherapy is often employed for the treatment of head and neck cancer. Unfortunately, its neurotoxic effects on normal brain tissue often compromise the quality of life (QOL) for survivors. Particularly, acute cognitive deficit (ACD), which can occur several days to one month after irradiation, limits its therapeutic use. Impairment of neurogenesis in the hippocampus plays a key role in the development of radiation-induced cognitive deficit, and brain-derived neurotrophic factor (BDNF) may be involved. In the present study, we re-evaluated the effects of different doses of radiation on the development of ACD in Sprague Dawley rats. Our results showed that 30 Gy, but not 2 Gy or 10 Gy of whole brain radiation (WBI), led to significant deficits in cognitive functions at one month post-irradiation. At 7 and 30 days post-irradiation, immunofluorescence showed WBI had seriously impeded the production of new neurons and shortened their survival time. Additionally, decreased bdnf mRNA and protein expression were also observed. A significant decrease in histone deacetylase 1 (HDAC1)-dependent H3 acetylation was observed at bdnf promoters by ChIP analysis. TSA, an HDAC inhibitor, triggered bdnf transcription and rescued neurogenesis impairment following WBI. In summary, our results suggest that a single-dose exposure to 30 Gy WBI induced acute cognitive dysfunction in rats. Additionally, radiation-induced persistent inhibition of bdnf gene transcription resulting from lowered rates of HDAC1-dependent H3 acetylation was associated with long-term impairment of neurogenesis in the denate gyrus (DG). Triggering of BDNF-TrkB signaling by inhibition of HDAC-1 may be used to stimulate neurogenesis., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Twenty-four 2-azetidinone derivatives have been designed and synthesized as cholesterol absorption inhibitors. All new compounds were evaluated for their activity to inhibit cholesterol absorption in hamsters, and most of them showed considerable effects in lowering the levels of total cholesterol in the serum, especially compound 2d, 4a, 4f, 4i and 4j.