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Renal fibrosis (RF) is a typical pathological presentation of end‐stage chronic kidney disease (CKD) and autosomal dominant polycystic kidney disease (ADPKD). However, the precise regulatory mechanisms governing this re‐expression process remain unclear. Differentially expressed microRNAs (miRNAs) associated with RF were screened by microarray analysis using the Gene Expression Omnibus (GEO) database. The miRNAs upstream of the genes in question were predicted using the miRWalk database. The miRNAs involved in the two GEO data sets were intersected to identify key miRNAs; their regulatory pathways were investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Subsequently, the effects and the underlying mechanisms of target miRNA on RF were examined in a unilateral ureteral obstruction (UUO)‐induced mice renal fibrotic model and a transforming growth factor‐β1 (TGF‐β1)‐induced tubular epithelium (HK‐2) fibrotic cell model. In total, 109 and 32 differentially expressed miRNAs were identified in the GSE133530 and GSE80247 data sets, respectively. GREM1 was identified as a hub gene, where its 2196 upstream miRNAs were predicted; miR‐574‐5p was found to be downregulated and closely related to fibrosis after data set intersection and enrichment analyses, thus was selected for further investigation. A differential expression heatmap (GSE162794) showed that miR‐542‐5p was downregulated. The expression of GREM1 mRNA was upregulated, whereas that of miR‐542‐5p was downregulated in UUO mice and fibrotic HK‐2 cells as compared with the relevant controls. The binding site of miR‐542‐5p was predicted at the 3'UTR region of GREM1 and was confirmed by subsequent dual luciferase reporter gene assay. Western blot analysis showed that Gremlin‐1 and Fibronectin were significantly upregulated after induction of TGF‐β1; when miR‐542‐5p was overexpressed or GREM1 mRNA was interfered, the upregulations of Gremlin‐1 and Fibronectin were significantly reduced. Our research demonstrates that miR‐542‐5p plays a critical role in the progression of RF, and thus may be a promising therapeutic target for CKD and ADPKD. [ABSTRACT FROM AUTHOR]

Highlights By applying an electric field, the thermal conductivity(λ) of composites can be enhanced through the induced orientation of high λ fillers within the matrix. As far as the DC electric field is concerned, the pattern of the electric field application time on the λ of the composites is not clear. In this work, a 400 V/mm DC electric field was selected to prompt the alignment of boron nitride (h‐BN) within the epoxy resin (EP) matrix, with an in‐depth analysis of how the timing of the electric field application influences the λ of the composites. Results demonstrate that the λ of h‐BN/EP composites exhibits a pattern of increasing, decreasing, then increasing and finally stabilizing when the electric field application time is 0–480 min. When the electric field was applied for 20 min, the composites exhibited a maximum λ of 0.544 W/(m K), a value that is 3.88 times of pure EP, and 2.32 times of that of the composites without electric field under the same filling content. In addition, the composite exhibits an AC breakdown field strength (Eb) that is slightly elevated compared to the pure EP. Boron nitride (h‐BN) was successfully oriented in epoxy resin (EP) matrix by electric field induction. λ of the composite is proportional to orientation Angle of h‐BN in the matrix. λ of composite can be increased by electric field induced fillers orientation. Electric field induction does not damage the insulation properties of composite. The excellent in‐plane λ and insulation properties of h‐BN are fully utilized. [ABSTRACT FROM AUTHOR]

Nonprobability samples, especially web survey data, have been available in many different fields. However, nonprobability samples suffer from selection bias, which will yield biased estimates. Moreover, missingness, especially nonignorable missingness, may also be encountered in nonprobability samples. Thus, it is a challenging task to make inference from nonprobability samples with nonignorable missingness. In this article, we propose a Bayesian approach to infer the population based on nonprobability samples with nonignorable missingness. In our method, different Logistic regression models are employed to estimate the selection probabilities and the response probabilities; the superpopulation model is used to explain the relationship between the study variable and covariates. Further, Bayesian and approximate Bayesian methods are proposed to estimate the response model parameters and the superpopulation model parameters, respectively. Specifically, the estimating functions for the response model parameters and superpopulation model parameters are utilized to derive the approximate posterior distribution in superpopulation model estimation. Simulation studies are conducted to investigate the finite sample performance of the proposed method. The data from the Pew Research Center and the Behavioral Risk Factor Surveillance System are used to show better performance of our proposed method over the other approaches. [ABSTRACT FROM AUTHOR]

Epoxy resin, as an adhesive for the main insulation system of large generators, has excellent insulation properties. But its poor thermal conductivity limits the capacity enhancement of large generators. Forming thermally conductive pathways by using electric field to induce high thermal conductivity fillers in the polymer can effectively improve the thermal conductivity of the composite at low loading condition. In this article, a DC electric field is used in epoxy resin (EP) to induce two‐dimensional inorganic fillers h‐BN deflection and head‐to‐tail lap, which can make the heat flow transfer along the in‐plane of the particles and contribute to the more efficient thermal conductivity network. A high thermal conductivity of 0.544 W/(m K) was achieved at a low load of 10 wt%, which has an improvement of 289% compared to pure EP (0.14 W/[m K]) and 130% compared to the randomly dispersed composite with the same load. The composites have excellent thermal conductivity as well as insulating properties, among which volume resistivity is 1.46 × 1012 Ω/cm, increasing by 61.4% compared to pure EP. This method is easy to be carried out in engineering and has great possibilities for the main insulation of large generators and even for other applications with high thermal conductivity electrical insulation. Highlights: The structure of composites was adjusted by direct current electric field.The high in‐plane thermal conductivity of h‐BN is fully exploited.The relationship between deflection angle of BN and thermal conductivity of composites was built. [ABSTRACT FROM AUTHOR]

Objective: To analyze the failure patterns in patients with different histological subtypes of sinonasal malignancies (SNMs). Study Design: Retrospectively gathered data. Setting: Academic university hospital. Methods: Patients with SNMs treated at a tertiary referral center between January 1999 and January 2019 were included. We assessed the failure patterns within different histological subtypes. Results: The study included 897 patients. The median follow‐up time was 100 months. Adenoid cystic carcinoma (ACC) had a moderate risk of developing local recurrence (LR) and distant metastasis (DM). Compared with ACC, squamous cell carcinoma (SCC), adenocarcinoma (AC), soft tissue sarcoma (STS), and mucosal melanoma (MM) were classified as a high LR risk group. For DM, neuroendocrine carcinoma (NEC), STS, and MM were in the high‐risk group. Conclusions: ACC had intermediate local and distant failure risks, while SCC, AC, STS, and MM were at high LR risks. NEC, STS, and MM were at high DM risk. [ABSTRACT FROM AUTHOR]

Focal segmental glomerulosclerosis (FSGS) is a type of chronic glomerular nephropathy showing characteristic glomerular sclerosis, diagnosed by kidney biopsy. However, it is difficult and expensive to monitor disease progression with repeated renal biopsy in clinical practice, and thus here we explored the feasibility of urine biomarkers as non‐invasive diagnostic tools. We downloaded scRNA‐seq datasets of 20 urine cell samples and 3 kidney tissues and obtained two gene lists encoding extracellular proteins for bioinformatic analysis; in addition, we identified key EP‐Genes by immunohistochemical staining and performed bulk RNA sequencing with 12 urine samples. We report that urine cells and kidney cells were correlated. A total of 64 EP‐Genes were acquired by intersecting genes of distal tubular cluster with extracellular proteins. Function enrichment analysis showed that EP‐Genes might be involved in the immune response and extracellular components. Six key EP‐Genes were identified and correlated with renal function. IMC showed that key EP‐Genes were located mainly in tubules. Cross verification and examination of a urine RNAseq dataset showed that SPP1 had diagnostic potential for FSGS. The presence of urine SPP1 was primarily associated with macrophage infiltration in kidney, and the pathogenesis of FSGS may be related to innate immunity. Urinary cells seemed to be strongly similar to kidney cells. In summary, SPP1 levels reflect renal function and may have potential as a biomarker for non‐invasive diagnosis of FSGS. [ABSTRACT FROM AUTHOR]

Purpose: The prognostic outcomes of metastasis patterns in patients with de novo metastatic breast cancer (dnMBC) of different ages are unknown. Our study used a large‐scale data to investigate the metastasis patterns and prognostic features in dnMBC of different ages. Methods: Total 24,698 women with dnMBC in the Surveillance, Epidemiology and End Results database (2010–2018) were divided into three groups by age. Chi‐squared test was used to compare metastasis patterns and logistic regression was performed to investigate the risk of age and specific organ metastases. Kaplan–Meier survival curves were used to compare the overall survival. Results: In three groups, young group had the largest proportion of liver metastases (35.2% vs. 28.2% vs. 21.1%, p < 0.001), and elderly group had the largest proportion of lung metastases (22.6% vs. 30.0% vs. 35.0%, p < 0.001) and the lowest proportion of bone metastases (65.7% vs. 67.6% vs. 64.4%, p < 0.001). In young group, patients with liver metastases had better prognosis than patients with lung metastases (MST: 34 months vs. 29 months, p = 0.041), but in middle‐aged and elderly groups, the prognosis of lung metastases was better than that of liver metastases (MST in middle‐aged group: 24 months vs. 20 months, p = 0.002; MST in elderly group: 12 months vs. 6 months, p < 0.001). Conclusion: DnMBC patients at different age have distinct metastasis patterns and prognostic features. The findings lend support to consideration of tailored management and surveillance strategies for different age patients. [ABSTRACT FROM AUTHOR]

Background: Identifying the lymph node target volume in patients with node‐negative sinonasal squamous cell carcinoma (SNSCC) crossing the midline poses a challenge. This study aims to address this. Methods: We retrospectively reviewed clinically N0 patients with tumors crossing the midline who received elective neck irradiation (ENI) from two centers between 1999 and 2019. The main endpoint was regional relapse‐free survival (RRFS). Results: We included 104 patients: 64 received bilateral ENI, and 40 received ipsilateral‐only ENI (median follow‐up time was 89.99 and 95.01 months, respectively). At 5 years, the RRFS rates were comparable (57.68% vs. 55.83%, p = 0.372), as were the contralateral RRFS (57.68% vs. 61.62%, p = 0.541). Five‐year OS, LRFS, and DMFS showed no significant difference between two groups. Conclusions: Our findings provide preliminary evidence suggesting the potential for avoiding contralateral ENI in SNSCC patients with midline crossing tumors who undergo ipsilateral ENI, covering at least level II. Validation through future prospective studies is necessary. [ABSTRACT FROM AUTHOR]

Purpose: To determine oncologic outcomes for patients with T4b sinonasal squamous cell carcinoma (SNSCC) treated with either surgery plus radiotherapy or definitive radiotherapy. Materials and Methods: Between January 1999 and December 2016, 85 patients with T4b SNSCC were analyzed retrospectively, there were 54 who received surgery plus radiotherapy (S + RT group) ± chemotherapy and 31 with definitive radiotherapy (RT group) ± chemotherapy. A 1: 2 propensity score matching (PSM) was performed to balance clinical factors and match patients. Kaplan–Meier method and Cox proportional hazard model were used to determine risk factors on survival outcomes. Results: The median follow‐up time was 76.7 months. The cumulative rates of locoregional control (LRC), distant metastasis‐free survival (DMFS), cancer‐specific survival (CSS), and overall survival (OS) at 5 years for entire cohort were 44.6%, 33.1%, 38.8%, and 33.9% respectively. After PSM, a total of 50 patients in S + RT group and 25 patients in RT group were analyzed. The 5‐year LRC, DMFS, CSS, and OS between S + RT and RT group were 58.6% versus 27.5% (p = 0.035), 42.8% versus 20.0% (p = 0.006), 50.3% versus 22.0% (p = 0.005), 44.5% veruss 20.0% (p = 0.004). The 5‐year survival rates with orbital retention between groups were 32.7% and 15.0%, p = 0.080. Multivariate Cox analysis revealed non‐surgical therapy (HR = 3.678, 95%CI 1.951–6.933) and invasion of cranial nerves (other than maxillary division of trigeminal nerves) (HR = 2.596, 95%CI 1.217–5.535) were associated with decreased OS. Conclusion: The inclusion of surgery in the multimodal management of T4b SNSCC might confer a survival benefit. Further prospective studies comparing the oncologic outcomes of S + RT with RT are warranted. Level of Evidence: 3 Laryngoscope, 133:2222–2231, 2023 [ABSTRACT FROM AUTHOR]

Objectives: To explore the prevalence of hypopharyngeal carcinoma (HPC) with synchronous second primary malignancies (Syn‐SPMs), their impact on clinical outcomes, and associated risk factors in the image‐enhanced endoscopy era. Materials and Methods: We retrospectively analyzed 673 patients newly diagnosed with HPC at our cancer center between 2009 and 2019. The patients were divided into three groups: (a) no second primary malignancies (N‐SPMs, n = 533); (b) synchronous carcinoma in situ (Syn‐Tis, n = 60); (c) synchronous invasive tumors (Syn‐invasive, n = 80). Propensity score matching was conducted to balance the N‐SPMs and Syn‐invasive groups at a 3:1 ratio. Results: Most (96.1%) underwent pretreatment esophagogastroduodenoscopy evaluation with image‐enhanced endoscopy. The incidence rates were: Syn‐SPMs, 20.8%; Syn‐Tis, 8.9%; Syn‐invasive, 11.9%. At a median follow‐up of 66.7 months, the Syn‐Tis and N‐SPMs groups had a similar 5‐year overall survival (OS; 45.6% vs. 44.5%; hazard ratio [HR], 0.956; 95% confidence interval [CI], 0.660–1.385; p = 0.806). Compared to the N‐SPMs group, the Syn‐invasive group had poorer 5‐year OS (27.0% vs. 52.9%; HR, 2.059; 95% CI, 1.494–2.839; p < 0.001). Alcohol consumption was significantly associated with Syn‐SPMs occurrence (odds ratio, 2.055, 2.414, and 3.807 for light, intermediate, and heavy drinkers, respectively). Conclusion: The prevalence of Syn‐SPMs among patients with HPC was high. Syn‐invasive SPMs decreased the survival of patients with HPC. Routine screening with image‐enhanced endoscopy should be recommended to detect early‐stage SPMs, especially for heavy alcohol drinkers. Level of Evidence: 3 Laryngoscope, 133:1906–1913, 2023 [ABSTRACT FROM AUTHOR]

The approximating sequence Riccati equation method is an efficient approach for solving the nonlinear optimal control problems, but its neglect of nonlinear dynamics and necessary optimality condition makes the control law difficult to satisfy the optimality. In this paper, an approximating pseudospectral method with state‐dependent coefficient optimization algorithm is proposed to solve this defect. By introducing the approximating pseudospectral method, the original nonlinear problem is transformed into a sequence of linear subproblems, which preserves the nonlinearity of solution. Then a state‐dependent coefficient optimization algorithm based on the gradient projection technique is proposed, which ensures the optimality of the control law. A double‐layer optimization structure is designed to facilitate the coordination between the approximating method and the optimization algorithm. Theoretical analysis proves the convergence of the proposed method. Comparative case studies illustrate the effectiveness in reducing the performance index and ensuring the optimality of the control law. [ABSTRACT FROM AUTHOR]

The theoretical properties of a novel time‐optimal L1$$ {L}^1 $$/L2$$ {L}^2 $$ norms optimal control for linear time‐invariant systems are investigated. The L0$$ {L}^0 $$‐optimal control (or sparsest control) is converted to the time‐optimal L1$$ {L}^1 $$/L2$$ {L}^2 $$ norms optimal control which can be solved efficiently. The proposed control is obtained via minimization of the time‐optimal L1$$ {L}^1 $$/L2$$ {L}^2 $$ norms optimal control input along with the constraints on the state variable. Subsequently, by using the nonsmooth maximum principle, the uniqueness and continuity of the optimal solution of the time‐optimal L1$$ {L}^1 $$/L2$$ {L}^2 $$ norms optimal control are proved. The superiority of the time‐optimal L1$$ {L}^1 $$/L2$$ {L}^2 $$ norms optimal control is illustrated by numerical examples. [ABSTRACT FROM AUTHOR]

Background: The necessity of level III irradiation in patients with node‐negative advanced sinonasal squamous cell carcinoma (SNSCC) is unclear. Methods: Seventy‐eight patients with advanced SNSCC were included. Survival rates were estimated and compared between treatment groups. Results: Twenty‐five patients received ipsilateral levels Ib and II irradiation (group 1) and 53 patients received ipsilateral levels Ib and II plus level III irradiation (group 2). The median follow‐up time was 75.56 months. Five‐year survival rates (regional relapse‐free survival, overall survival, local relapse‐free survival, and distant metastasis‐free survival) were similar between groups 1 and 2 (all p > 0.05). Irradiation doses to the thyroid and larynx were significantly lower in group 1 than in group 2. Conclusions: Ipsilateral irradiation of levels Ib and II neck provides similar regional control and results as irradiation of these levels plus level III, with lower irradiation doses to normal neck tissue, in patients with node‐negative advanced SNSCC. [ABSTRACT FROM AUTHOR]

This paper proposes a novel adaptive pseudospectral (NAP) method for solving the time‐energy optimal control model to minimize the parking time and the energy output of the vehicle. The time‐energy optimal control model is first discretized into a nonlinear programming problem at Gauss collocations by the NAP method. Subsequently, we prove the equivalence between the nonlinear programming problem derived from the NAP method and the time‐energy optimal control model problem. Compared to those of the interior point method and the piecewise gauss pseudospectal method, simulation results show that the NAP method has higher computational efficiency and accuracy in solving the time‐energy optimal control model problem. [ABSTRACT FROM AUTHOR]

Endolysosomes are key regulators of iron metabolism and are central to iron trafficking and redox signaling. Iron homeostasis is linked to endolysosome acidity and inhibition of endolysosome acidity triggers iron dysregulation. Because of the physiological importance and pathological relevance of ferrous iron (Fe2+), we determined levels of Fe2+ specifically and quantitatively in endolysosomes as well as the effects of Fe2+ on endolysosome morphology, distribution patterns, and function. The fluorescence dye FeRhoNox‐1 was specific for Fe2+ and localized to endolysosomes in U87MG astrocytoma cells and primary rat cortical neurons; in U87MG cells the endolysosome concentration of Fe2+ ([Fe2+]el) was 50.4 μM in control cells, 73.6 μM in ferric ammonium citrate (FAC) treated cells, and 12.4 μM in cells treated with the iron chelator deferoxamine (DFO). Under control conditions, in primary rat cortical neurons, [Fe2+]el was 32.7 μM. Endolysosomes containing the highest levels of Fe2+ were located perinuclearly. Treatment of cells with FAC resulted in endolysosomes that were less acidic, increased in numbers and sizes, and located further from the nucleus; opposite effects were observed for treatments with DFO. Thus, FeRhoNox‐1 is a useful probe for the study of endolysosome Fe2+, and much more work is needed to understand better the physiological significance and pathological relevance of endolysosomes classified according to their heterogeneous iron content Cover Image for this issue:https://doi.org/10.1111/jnc.15396 [ABSTRACT FROM AUTHOR]

Purpose: Conditional survival (CS) and failure hazard estimations can provide important dynamic prognostic information for clinical decision‐making and surveillance counseling. The current study aimed to investigate the CS and dynamic failure hazard in non‐metastatic nasopharyngeal carcinoma (NPC) treated with intensity‐modulated radiotherapy (IMRT). Methods: Conditional overall survival (COS) and progression‐free survival (CPFS) estimates adjusted for age and gender against each AJCC 8th stage were calculated. Multivariable Cox regression (MCR) models were fitted in the entire population at baseline and subsequently separate MCR models were fitted in patients who have maintained event‐free time of 1 to 10 years to generate respective hazard ratio (HR). Annual hazard rates of death and progression over 10 years for each stage were also estimated. Results: A total of 1993 patients were eligible for analysis. The estimated 5‐year OS and PFS for entire cohort were 79.0% and 70.7% at initial diagnosis. After 5 years of event‐free follow‐up, additional 5‐year COS and CPFS increased to 85.9% and 85.5%, respectively. Stage I/II maintained dramatically favorable CS and low hazard (< 5%) of death and progression over time. Relative to stage I/II, stage III manifested non‐significantly higher failure hazard for the first 3 years of survivorship and approached to similar level of stage I/II afterwards. Stage IVA presented most impressive improvement in terms of both COS (∆=9.8%) and CPFS (∆ = 16.8%) whereas still drastically inferior to that of stage I‐III across all conditional time points. After 4 years of follow‐up, progression hazard of stage IVA became relatively steady of approximate 6%. Conclusions: Survival prospect of non‐metastatic NPC improves over years with distinct dynamic patterns across stages, providing important implications for personalized decision‐making in terms of both clinical management and surveillance counseling. Stage‐dependent and hazard‐adapted clinical management and surveillance are warranted. [ABSTRACT FROM AUTHOR]

Background: Esthesioneuroblastoma (ENB) is a rare malignant neoplasm. Currently, no consistent and universal staging system for ENB exists. The aim of this study is to propose a TNM‐based classification. Subjects and methods: Hundred and forty‐two patients from our institution, with ENB pathologically confirmed between July 1978 and December 2018, were reviewed. All patients were restaged according to the Kadish stage, Morita stage and American Joint Committee on Cancer (AJCC) T classification from clinical and radiological data. Multivariate Cox proportional hazard regression analyses were performed to determine the impact of various factors. The goodness‐of‐fit and predictive accuracy of the different staging systems were calculated using R software. Results: The median follow‐up time was 57 months (range: 4‐229 months). According to the Kadish system, the 5‐year overall survival (OS) for patients with stage A, B and C was 100%, 83.6% and 64.2%, respectively (P =.055). With respect to the Morita classification, 5‐year OS for stages A, B, C and D was 100%, 83.6%, 70.7% and 50.0%, respectively (P =.004). Analysis based on the proposed staging model demonstrated 5‐year OS for stage I, II, III and IV disease was 100%, 88.9%, 75.9% and 49.0%, respectively (P <.001). In separate multivariate Cox regression models, only the novel staging system exhibited independent effects on OS (P =.004); the Akaike information criterion and Harrell's concordance index were also superior to those calculated for the Kadish or Morita systems. Conclusions: The proposed TNM‐based staging system offers an improved prognostic assessment for patients with ENB. Further verification and refinement from additional dataset application is required. [ABSTRACT FROM AUTHOR]

Using a simple one‐step hydrothermal method, benzyl triethylammonium chloride was used to assist the synthesis of double core‐shell oxygen‐incorporated molybdenum disulfide (DB‐O‐MoS2), and its friction and wear properties were measured on the MRS‐10A four‐ball testing machine. They were characterised by X‐ray diffraction, scanning electron microscope, transmission electron microscope, thermogravimetry, Brunner−Emmet−Teller and Fourier transform infrared spectroscope. Friction and wear properties of DB‐O‐MoS2 were measured at different concentrations. The results showed that the tribological properties of SN 5W‐40 base oil have been improved by adding the DB‐O‐MoS2 as lubricant additives. The possibility of DB‐O‐MoS2 mechanisms by which the nanolubricants improved the tribological properties were put forward. Therefore, research on DB‐O‐MoS2 is beneficial to the development of new engine lubricant additives. [ABSTRACT FROM AUTHOR]

Objective To explore high-resolution computed tomography (HRCT) characteristics of arytenoid cartilage in patients with laryngeal contact granuloma (LCG). Setting Tertiary hospitals. Study Design Individual case-control study. Methods HRCT scans were obtained before treatment from 42 patients with LCG. Similar scans were obtained from 50 patients with glottic laryngeal cancer or vocal cord leukoplakia without vocal process involvement. Results Forty-two male patients with LCG were enrolled in the study. There were 41 patients with unilateral vocal cord lesions, and 1 patient had bilateral lesions. All 50 eligible patients in the laryngeal lesion group were men. There were 39 patients with unilateral lesions, and 11 had bilateral lesions. The rate of arytenoid cartilage sclerosis in the LCG group was 79.07% (34/43) on the lesion side and 7.32% (3/41) on the healthy side. In the laryngeal lesion group, the rate of arytenoid cartilage sclerosis was 13.11% (8/61) on the lesion side and 2.56% (1/39) on the healthy side. The rate of arytenoid cartilage sclerosis on the lesion side of patients with LCG was significantly higher than on the healthy side of patients with LCG and significantly higher than both the healthy and lesion sides of patients with laryngeal lesions ( P < .001). Conclusions Arytenoid cartilage sclerosis was observed on the lesion side in most patients with LCG, and the presence of sclerosis may support the diagnosis of LCG. [ABSTRACT FROM AUTHOR]

Background It has been reported that the calcium sensing receptor ( CaSR), a widely expressed G protein-coupled receptor, can stimulate cell differentiation and proliferation. However, in malignant tumors, loss of CaSR expression has been associated with tumorigenesis, metastasis, and progression. Recent studies have indicated that the CaSR could promote the expression of E-cadherin, which was considered a tumor suppressor. However, in human lung adenocarcinoma, the importance of the CaSR and E-cadherin has not been sufficiently investigated. Methods Expression levels of CaSR and E-cadherin in paraffin sections from 117 resected lung adenocarcinoma patients were evaluated by immunohistochemistry. We analyzed the correlation between our target proteins and clinical variables. Clinical significance was analyzed by multivariate Cox regression analysis, Kaplan- Meier curve, and log-rank test. Results Expression of the CaSR in lung adenocarcinoma tissue was significantly lower than in the normal sample ( P = 0.003). Kendall tau-b analysis showed that, in a lung adenocarcinoma sample, the expression of CaSR positively correlated with a high level of E-cadherin ( P < 0.001). Lung adenocarcinoma patients with a strong expression of CaSR ( P = 0.034) or E-cadherin ( P = 0.001) had longer overall survival. Multivariate Cox proportional hazards model analysis showed that the combined marker was an independent prognostic indicator of overall survival (hazard ratio = 0.440, confidence interval = 0.249-0.779, P = 0.005). Conclusions We identified the CaSR as a new prognostic biomarker in lung adenocarcinoma. These results also suggested that the CaSR may become a new therapeutic target of lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: This study presents the characteristics and treatment of small cell lung cancer (SCLC) and an analysis of the factors that impact survival in northeastern Chinese populations, among both smokers and non-smokers. Methods: A retrospective review was performed using 485 Chinese patients diagnosed with pathologically confirmed SCLC diagnoses between January 2001 and December 2007. Data on patient characteristics, treatment patterns, and outcome information was collected systematically. Univariate analysis and the Cox multivariate regression model were used to evaluate prognostic factors. Results: Median survival time was 16 months in all patients, 31 months in limited stage (LS) patients, and 10 months in extensive-stage (ES) patients. Never-smoking patients ( P= 0.0368) with good performance status (PS) ( P= 0.0044) or with normal lactate dehydrogenase (LDH) levels ( P < 0.0001), demonstrated superior survival rates. Multivariate analysis identified that cycles of chemotherapy, PS, LDH levels, recurrence or progression, and clinical stage were each independent prognostic factors applicable to all patients. In LS-SCLC, cycles of chemotherapy were the only prognostic indicator; however, cycles of chemotherapy, LDH levels, and recurrence or progression, were all significant factors in ES-SCLC. Conclusion: Cycles of chemotherapy, PS, LDH levels, recurrence or progression, and clinical stage were proved to be independent prognostic factors for SCLC with variant value based on the SCLC tumor stage. [ABSTRACT FROM AUTHOR]

Rapid inactivation of metabolism is essential for accurately determining the concentrations of metabolic intermediates in the in vivo state. We compared a broad spectrum of energetic intermediate metabolites and neurotransmitters in brains obtained by microwave irradiation to those obtained by freeze blowing, the most rapid method of extracting and freezing rat brain. The concentrations of many intermediates, cytosolic free NAD( P)+/ NAD( P) H ratios, as well as neurotransmitters were not affected by the microwave procedure. However, the brain concentrations of ATP were about 30% lower, whereas those of ADP, AMP, and GDP were higher in the microwave-irradiated compared with the freeze-blown brains. In addition, the hydrolysis of approximately 1 μmol/g of ATP, a major in vivo Mg2+-binding site, was related to approximately five-fold increase in free [Mg2+] (0.53 ± 0.07 mM in freeze blown vs. 2.91 mM ± 0.48 mM in microwaved brains), as determined from the ratio [citrate]/[isocitrate]. Consequently, many intracellular properties, such as the phosphorylation potential and the ∆G' of ATP hydrolysis were significantly altered in microwaved tissue. The determinations of some glycolytic and TCA cycle metabolites, the phosphorylation potential, and the ∆G' of ATP hydrolysis do not represent the in vivo state when using microwave-fixed brain tissue. [ABSTRACT FROM AUTHOR]

A glassy carbon electrode (GCE) was covalently modified by 4-phosphatephenyl (4-PP). Sensing paracetamol (PCT) via linear sweep voltammetry in sulfuric buffer solution of pH 1.02 at 36.8 °C, the 4-PP-modified GCE showed high electrochemical sensitivity and long reusability. PCT-loaded poly(vinyl alcohol) (PVA) nanofibers were prepared by electrospinning. Based on the calibration curve of PCT on the 4-PP-modified GCE, the PCT release process from the nanofibers was electrochemically monitored in real time via two routes. The results showed that the covalently modified GCE can be repeatedly used as real-time electrochemical monitoring platform for drug release from drug-loaded nanofibers in the long term. [ABSTRACT FROM AUTHOR]

J. Neurochem. (2012) 122, 382-391. Abstract HIV-1-associated neurocognitive disorder (HAND) is a syndrome that ranges clinically from subtle neuropsychological impairments to profoundly disabling HIV-associated dementia. Not only is the pathogenesis of HAND unclear, but also effective treatments are unavailable. The HIV-1 transactivator of transcription protein (HIV-1 Tat) is strongly implicated in the pathogenesis of HAND, in part, because of its well-characterized ability to directly excite neurons and cause neurotoxicity. Consistent with previous findings from others, we demonstrate here that HIV-1 Tat induced neurotoxicity, increased intracellular calcium, and disrupted a variety of mitochondria functions, such as reducing mitochondrial membrane potential, increasing levels of reactive oxygen species, and decreasing bioenergetic efficiency. Of therapeutic importance, we show that treatment of cultured neurons with ketone bodies normalized HIV-1 Tat induced changes in levels of intracellular calcium, mitochondrial function, and neuronal cell death. Ketone bodies are normally produced in the body and serve as alternative energy substrates in tissues including brain and can cross the blood-brain barrier. Ketogenic strategies have been used clinically for treatment of neurological disorders and our current results suggest that similar strategies may also provide clinical benefits in the treatment of HAND. [ABSTRACT FROM AUTHOR]

PTHrP gene-expression products are generally of very low abundance. The PTHrP-lacZ knockin mouse is a useful tool in this regard, identifying PTHrP expression in previously unrecognized sites and serving to score this expression in gene-regulation experiments. These sites include the periosteum and ligament/tendon insertion sites at the surface of endochondral bones, in which PTHrP appears to regulate subjacent bone cell populations. As mesenchymal condensations chondrify, PTHrP/lacZ is also expressed in epiphyseal cartilage (the chondroepiphysis), and this structure contributes PTHrP-expressing chondrocyte populations to both articular cartilage and growth-plate cartilage when these structures take shape postnatally. The Indian hedgehog-PTHrP axis is fully deployed in both of these locations and in articular cartilage appears to protect the joint space from invasion by mineralizing cells. In most of these sites PTHrP is mechanically regulated. [ABSTRACT FROM AUTHOR]

Objective: Chondrocytes of the epiphyseal growth zone are regulated by the Indian hedgehog (IHH)-parathyroid hormone-related protein (PTHrP) axis. In weight-bearing joints, this growth zone comes to be subdivided by the secondary ossification center into distinct articular and growth cartilage structures. The purpose of this study was to explore the cells of origin, localization, regulation of expression, and putative functions of IHH and PTHrP in articular cartilage in the mouse., Methods: We assessed IHH and PTHrP expression in an allelic PTHrP-LacZ-knockin mouse and several versions of PTHrP-null mice. Selected joints were unloaded surgically to examine load-induction of PTHrP and IHH., Results: The embryonic growth zone appears to serve as the source of PTHrP-expressing proliferative chondrocytes that populate both the forming articular cartilage and growth plate structures. In articular cartilage, these cells take the form of articular chondrocytes in the midzone. In PTHrP-knockout mice, mineralizing chondrocytes encroach upon developing articular cartilage but appear to be prevented from mineralizing the joint space by IHH-driven surface chondrocyte proliferation. In growing and adult mice, PTHrP expression in articular chondrocytes is load-induced, and unloading is associated with rapid changes in PTHrP expression and articular chondrocyte differentiation., Conclusion: We conclude that the IHH-PTHrP axis participates in the maintenance of articular cartilage. Dysregulation of this system might contribute to the pathogenesis of arthritis.