Modulating the d-Band Center of Palladium via Ethylene Glycol Modification: Accelerating Had Desorption for Enhanced Formate Electrooxidation.

This study addresses the critical challenge in alkaline direct formate fuel cells (DFFCs) of slow formate oxidation reaction (FOR) kinetics as a result of strong hydrogen intermediate (Had) adsorption on Pd catalysts. We developed WO3-supported Pd nanoparticles (EG-Pd/WO3) via an organic reduction method using ethylene glycol (EG), aiming to modulate the d-band center of Pd and alter Had adsorption dynamics. Cyclic voltammetry demonstrated significantly improved Had desorption kinetics in EG-Pd/WO3 catalysts. Density functional theory (DFT) calculations revealed that the presence of EG reduces the d-band center of Pd, leading to weaker Pd-H bonds and enhanced Had desorption during the FOR. This research provides a new approach to optimize catalyst efficiency in DFFCs, highlighting the potential for more effective and sustainable energy solutions through advanced material engineering.

[Retracted] Long non­coding RNA SNHG6 promotes tumorigenesis in melanoma cells via the microRNA­101­3p/RAP2B axis.

[This retracts the article DOI: 10.3892/ol.2020.12186.].

Effect of buttress plate in Herscovici type D vertical medial malleolar fractures and peripheral fractures: a retrospective comparative cohort study.

BACKGROUND: The purpose of current retrospective study was to review the surgical methods and to evaluate the clinical efficacy of supporting plate for the treatment of vertical medial malleolus fractures on the basis of stable fixation of ipsilateral fibula. METHODS: This retrospective study included a total of 191 patients with vertical medial malleolus fractures. Patients enrolled were divided into simple vertical medial malleolus fractures and complex types of fractures. General demographic information and surgical information, including age, sex, surgical procedure and postoperative complications, were collected. The functional prognosis of patients was evaluated by American Orthopedic Foot and Ankle Society Ankle-Hindfoot Score (AOFAS) and Visual Analog Scale (VAS). RESULT: Among patients with simple vertical fractures, the respective incidence of internal fixation failure in screw group, buttress plate group, and screw combined buttress plate fixation group (combined fixation group) was 10/61 (16.4%),1/54 (7.4%) and 1 (1.9%), and the difference was statistically significant (P = 0.024). The incidence of abnormal fracture growth and healing in screw group, buttress plate group and combined fixation group was, respectively, 13/61 (21.3%), 6/54 (12.5%) and 2 (3.85%), with statistically significant difference (P = 0.019). In the patients with complex types of fractures, after 2 years of postoperative follow-up, the AOFAS score and VAS score of the following subgroups had good results: 91.18 ± 6.05 and 2.18 ± 1.08 in patients with joint surface collapse, and 92.50 ± 4.80 and 2.50 ± 1.29 in patients with tibial fractures, with 100% excellent and good rate. CONCLUSION: For simple and complex vertical medial malleolus fractures, buttress plate showed excellent fixation. Despite poor wound healing and extensive soft tissue dissection with this approach, buttress plate may provide a novel insight into medial malleolar fractures, especially for extremely unstable medial malleolar fractures.

Therapeutic Effects of Salvianolic Acid B on Angiotensin II-Induced Atrial Fibrosis by Regulating Atrium Metabolism via Targeting AMPK/FoxO1/miR-148a-3p Axis.

The present study highlights the effects of salvianolic acid B (Sal B) on angiotensin II (Ang II)-activated atrial fibroblasts as well as the associated potential mechanism from the metabonomics perspective. Metabolic profile analysis performed an optimal separation of the Ang II and control group, indicating a recovery impact of Sal B on Ang II-activated fibroblasts (FBs). We found that metabolite levels in the Ang II + Sal B group were reversed to normal. Moreover, 23 significant metabolites were identified. Metabolic network analysis indicated that these metabolites participated in purine metabolism and FoxO signaling pathway. We found that Sal B activated AMP-activated protein kinase (AMPK) phosphorylation, which further promoted FoxO1 activation and increased miR-148a-3p level. We further verified that Sal B modulate the abnormal AMP, phosphocreatine, glutathione (GSH), and reactive oxygen species (ROS) production in Ang II-stimulated FBs. Collectively, Sal B can protect the Ang II-activated FBs from fibrosis and oxidative stress via AMPK/FoxO1/miRNA-148a-3p axis.

A prospective, open-label, multicenter phase IV clinical trial on the safety and efficacy of lobaplatin-based chemotherapy in advanced breast cancer.

Background: Since lobaplatin (LBP) has been approved to treat metastatic breast cancer in China, this study aimed to evaluate the safety and efficacy of LBP-based chemotherapy in clinical practice. Methods: This trial was a prospective, open-label, multicenter phase IV clinical trial that enrolled patients with unresectable locally advanced or recurrent/metastatic breast cancer from 34 sites between July 2013 and March 2017. Patients were treated with LBP monotherapy or in combination for four to six cycles. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Results: A total of 1179 patients were analyzed; 59 (5.0%) were treated with LBP alone, 134 (11.4%) with LBP plus paclitaxel, 263 (22.3%) with LBP plus docetaxel, 237 (20.1%) with LBP plus gemcitabine, 403 (34.2%) with LBP plus vinorelbine, and 83 (7.0%) with other LBP-based regimens. The overall incidence of adverse events (AEs) was 95.2%, and 57.9% of patients had grade >3 AEs. The most common grade >3 AEs were neutropenia (43.9%), leukopenia (39.4%), anemia (17.8%), and thrombopenia (17.7%). LBP monotherapy showed the lowest incidence of grade >3 AEs (39.0%), followed by LBP plus docetaxel (52.9%), LBP plus paclitaxel (59.0%), LBP plus vinorelbine (62.5%), and LBP plus gemcitabine (62.9%). The ORR and DCR were 36.8 and 77.0%, respectively. The median PFS was 5.5 months (95% confidence interval: 5.2-5.9). Conclusion: LBP-based chemotherapy shows favorable efficacy in patients with advanced breast cancer, with manageable safety profile. Trial registration: This trial was registered with ChiCTR.org.cn, ChiCTR-ONC-13003471.

Ecological and human health risk assessment of heavy metal(loid)s in agricultural soil in hotbed chives hometown of Tangchang, Southwest China.

To determine the heavy metal(loid)s (HMs) contamination of agricultural soil in hotbed chives hometown of Tangchang, 788 topsoil samples were collected and analyzed for their heavy metal(loid)s concentration. The index of geo-accumulation (Igeo), pollution index (PI) and potential ecological risk index (EIi) were used to assess the degree of pollution. Correlation analysis and principal component analysis (PCA) were used to determine the sources of soil HMs. Human health risks estimated with hazard index (HI) and carcinogenic risk (CR) indices based on ingestion, inhalation and dermal exposure pathways for adults and children. The mean values of Cd, Hg, As, Pb, Cr, Cu, Ni and Zn were 0.221, 0.155, 9.76, 32.2, 91.9, 35.2, 37.1 and 108.8 mg kg-1, respectively, which did not exceed the threshold values of the risk screening value for soil contamination. The potential ecological risk of soil heavy metal(loid)s was low level and there was no significant human health risk. Based on PCA, Pb and Hg may originate from transportation and atmospheric deposition, Zn, Cr and Ni may originate from natural sources and industrial activities, and Cu and Cd may originate from agricultural activities. Overall, from the perspective of HMs content, the soil quality in this study area was at a clean level. This study provides a reference and a basis for formulating effective measures to prevent and control HMs enrichment in agricultural soils.

Long non-coding RNA SNHG6 promotes tumorigenesis in melanoma cells via the microRNA-101-3p/RAP2B axis.

Numerous studies have reported that the long non-coding RNA (lncRNA) small nucleolar RNA host gene 6 (SNHG6; ENSG00000245910) participates in the development of malignant tumors. However, the underlying mechanism of SNHG6 in the development of melanoma remains unknown. Thus, the present study aimed to investigate the biological role of SNHG6 in the progression of melanoma. SNHG6 expression in melanoma tissues and cells was assessed using a bioinformatics approach and reverse transcription-quantitative PCR analysis. Cell viability was determined using the Cell Counting Kit-8 and colony formation assays. The correlation between microRNA (miR)-101-3p, SNHG6 and RAP2B expression levels was assessed using Pearson's correlation analysis. Bioinformatic analysis and luciferase reporter assay were utilized to confirm the interaction between miR-101-3p and SNHG6 or RAP2B. The Transwell assay was conducted to examine the migratory and invasive activities of melanoma cells. In the present study, SNHG6 expression was upregulated in melanoma tissues and cell lines, and SNHG6 silencing suppressed melanoma cell viability, migration and invasion. SNHG6 was directly bound to miR-101-3p, which interacted with RAP2B. In addition, miR-101-3p expression was negatively correlated with SNHG6 or RAP2B expression. miR-101-3p silencing partially abrogated the suppressive effect of SNHG6-knockdown on RAP2B expression. Moreover, the data demonstrated that RAP2B overexpression reversed the inhibitory effects on melanoma cell proliferation, migration and invasion induced by SNHG6 silencing. In conclusion, the present study identified that SNHG6 accelerated melanoma progression via regulating the miR-101-3p/RAP2B axis. Thus, the SNHG6/miR-101-3p/RAP2B signaling pathway may be a novel therapeutic target for melanoma.

Correlations of HACE1 expression with pathological stages, CT features and prognosis of hepatocellular carcinoma patients.

PURPOSE: To explore the correlations of HECT domain and ankyrin repeat-containing E3 ubiquitin protein ligase 1 (HACE1) expression with the pathological stages, computed tomography (CT) features and prognosis of patients with hepatocellular carcinoma (HCC). METHODS: The clinical data were randomly collected from 70 patients with primary HCC. The messenger RNA (mRNA) and HACE1 in the cancer and paracancer tissues were determined via real-time quantitative-polymerase chain reaction (qRT-PCR). The curve of the relationship between HACE1 expression and patients' overall survival (OS) was plotted using the Kaplan-Meier method. Finally, the CT imaging data of patients were pooled to analyze the relationships of HACE1 expression with CT signs. RESULTS: Compared with those in the paracancer tissues, the mRNA and protein expression levels of HACE1 declined significantly in HCC tissues (p<0.05). It was found through analyzing the clinical indicators that the expression level of HACE1 was considerably correlated with the tumor diameter, tumor-node-metastasis (TNM) stages and pathological grades (p<0.05). The survival analysis revealed that the OS of patients in Low HACE1 group was shorter than that in High HACE1 group (median OS: 12.40 months vs. 15.16 months, p=0.031). Besides, as indicated by CT examination, the expression of HACE1 was not correlated with the number of tumors (p>0.05), but notably associated with the size, capsule and necrosis of tumors (p<0.05). CONCLUSIONS: HCC tissues are significantly deficient in HACE1, and the combination of HACE1 and CT images may serve as an efficacious strategy for the clinical diagnosis and monitoring of HCC.

Array testing for multiplex assays.

Group testing involves pooling individual specimens (e.g., blood, urine, swabs, etc.) and testing the pools for the presence of disease. When the proportion of diseased individuals is small, group testing can greatly reduce the number of tests needed to screen a population. Statistical research in group testing has traditionally focused on applications for a single disease. However, blood service organizations and large-scale disease surveillance programs are increasingly moving towards the use of multiplex assays, which measure multiple disease biomarkers at once. Tebbs and others (2013, Two-stage hierarchical group testing for multiple infections with application to the Infertility Prevention Project. Biometrics69, 1064-1073) and Hou and others (2017, Hierarchical group testing for multiple infections. Biometrics73, 656-665) were the first to examine hierarchical group testing case identification procedures for multiple diseases. In this article, we propose new non-hierarchical procedures which utilize two-dimensional arrays. We derive closed-form expressions for the expected number of tests per individual and classification accuracy probabilities and show that array testing can be more efficient than hierarchical procedures when screening individuals for multiple diseases at once. We illustrate the potential of using array testing in the detection of chlamydia and gonorrhea for a statewide screening program in Iowa. Finally, we describe an R/Shiny application that will help practitioners identify the best multiple-disease case identification algorithm.

Nicotine exerts neuroprotective effects by attenuating local inflammatory cytokine production following crush injury to rat sciatic nerves.

Recent studies have demonstrated that nicotine exhibited anti-inflammatory and neuroprotective properties by interacting with the alpha 7 nicotinic acetylcholine receptor (α7nAChR). However, the role of nicotine in regeneration during peripheral nerve injury has not been elucidated. The aim of this study was to investigate whether nicotine down-regulated production of proinflammatory cytokines and promoted peripheral nerve regeneration in rats. Rats challenged with sciatic nerve crush injury were treated with nicotine (1.5 mg/kg), three times per day. The expression of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin (IL-1ß), pinch test results, growth-associated protein 43 (GAP-43) expression, morphometric analyses, and the sciatic functional indexes were determined in sciatic nerves. Treatment with nicotine decreased local levels of TNF-α and IL-1ß, and increased the expression of GAP-43. Nicotine also improved nerve regeneration and functional recovery. The overall protective effects of nicotine were reversed by concomitant treatment with α7nACHR antagonist methyllycaconitine, indicating that nicotine exerted its specific anti-inflammatory and neuroprotective effects through the α7nAChR. These findings show that nicotine administration can provide a potential therapeutic pathway for the treatment of peripheral nerve injury, by a direct protective effect through the α7nAChR-mediated cholinergic anti-inflammatory pathway.

Regression analysis and variable selection for two-stage multiple-infection group testing data.

Group testing, as a cost-effective strategy, has been widely used to perform large-scale screening for rare infections. Recently, the use of multiplex assays has transformed the goal of group testing from detecting a single disease to diagnosing multiple infections simultaneously. Existing research on multiple-infection group testing data either exclude individual covariate information or ignore possible retests on suspicious individuals. To incorporate both, we propose a new regression model. This new model allows us to perform a regression analysis for each infection using multiple-infection group testing data. Furthermore, we introduce an efficient variable selection method to reveal truly relevant risk factors for each disease. Our methodology also allows for the estimation of the assay sensitivity and specificity when they are unknown. We examine the finite sample performance of our method through extensive simulation studies and apply it to a chlamydia and gonorrhea screening data set to illustrate its practical usefulness.

Adaptive elastic net for group testing.

For disease screening, group (pooled) testing can be a cost-saving alternative to one-at-a-time testing, with savings realized through assaying pooled biospecimen (eg, urine, blood, saliva). In many group testing settings, practitioners are faced with the task of conducting disease surveillance. That is, it is often of interest to relate individuals' true disease statuses to covariate information via binary regression. Several authors have developed regression methods for group testing data, which is challenging due to the effects of imperfect testing. That is, all testing outcomes (on pools and individuals) are subject to misclassification, and individuals' true statuses are never observed. To further complicate matters, individuals may be involved in several testing outcomes. For analyzing such data, we provide a novel regression methodology which generalizes and extends the aforementioned regression techniques and which incorporates regularization. Specifically, for model fitting and variable selection, we propose an adaptive elastic net estimator under the logistic regression model which can be used to analyze data from any group testing strategy. We provide an efficient algorithm for computing the estimator along with guidance on tuning parameter selection. Moreover, we establish the asymptotic properties of the proposed estimator and show that it possesses "oracle" properties. We evaluate the performance of the estimator through Monte Carlo studies and illustrate the methodology on a chlamydia data set from the State Hygienic Laboratory in Iowa City.

Retraction: Yang, C., et al. miR-126 Functions as a Tumor Suppressor in Osteosarcoma by Targeting Sox2. Int. J. Mol. Sci. 2014, 15, 423-437, doi:10.3390/ijms15010423.

Experimental results from [...].

Exosomes Isolated From Human Umbilical Cord Mesenchymal Stem Cells Alleviate Neuroinflammation and Reduce Amyloid-Beta Deposition by Modulating Microglial Activation in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by excessive accumulation of the amyloid-ß peptide (Aß) in the brain, which has been considered to mediate the neuroinflammation process. Microglial activation is the main component of neuroimmunoregulation. In recent years, exosomes isolated from human umbilical cord mesenchymal stem cells (hucMSC-exosomes) have been demonstrated to mimic the therapeutic effects of hucMSCs in many inflammation-related diseases. In this study, exosomes from the supernatant of hucMSCs were injected into AD mouse models. We observed that hucMSC-exosomes injection could repair cognitive disfunctions and help to clear Aß deposition in these mice. Moreover, we found that hucMSC-exosomes injection could modulate the activation of microglia in brains of the mice to alleviated neuroinflammation. The levels of pro-inflammatory cytokines in peripheral blood and brains of mice were increased and the levels of anti-inflammatory cytokines were decreased. We also treated BV2 cells with hucMSC-exosomes in culture medium. HucMSC-exosomes also had inflammatory regulating effects to alternatively activate microglia and modulate the levels of inflammatory cytokines in vitro.

Spatially Modeling the Effects of Meteorological Drivers of PM2.5 in the Eastern United States via a Local Linear Penalized Quantile Regression Estimator.

Fine particulate matter (PM2.5) poses a significant risk to human health, with long-term exposure being linked to conditions such as asthma, chronic bronchitis, lung cancer, atherosclerosis, etc. In order to improve current pollution control strategies and to better shape public policy, the development of a more comprehensive understanding of this air pollutant is necessary. To this end, this work attempts to quantify the relationship between certain meteorological drivers and the levels of PM2.5. It is expected that the set of important meteorological drivers will vary both spatially and within the conditional distribution of PM2.5 levels. To account for these characteristics, a new local linear penalized quantile regression methodology is developed. The proposed estimator uniquely selects the set of important drivers at every spatial location and for each quantile of the conditional distribution of PM2.5 levels. The performance of the proposed methodology is illustrated through simulation, and it is then used to determine the association between several meteorological drivers and PM2.5 over the Eastern United States (US). This analysis suggests that the primary drivers throughout much of the Eastern US tend to differ based on season and geographic location, with similarities existing between "typical" and "high" PM2.5 levels.

Integrated analysis reveals candidate mRNA and their potential roles in uterine leiomyomas.

AIM: Uterine leiomyomas (UL) are the most common pelvic tumors, and the etiology and pathophysiology are not well understood. We aimed to elucidate the genes responsible for UL development. METHODS: Integrated analyses of four datasets of mRNA profiling for UL were performed. Functional annotation of differentially expressed genes (DEG) was used to systematically characterize the global expression profiles. The UL-specific protein-protein interaction network was constructed. RESULTS: Integrated analysis led to the discovery of 2167 DEG (1042 upregulated and 1125 downregulated). The aberrant expression of NAV2, KIF5C, DCX, CAPN6, COL4A2, ALDH1A1, and DPT may play important roles in UL tumorigenesis. In addition, the dysregulation of MEST, LGALS3, and TLR3 may be involved in the progression of UL by a common mechanism. Functional annotation showed that extracellular matrix receptor interaction may be more active and cause the extracellular matrix abnormally formed in UL. Moreover, focal adhesion and cell adhesion molecules may play roles in the development of UL. Furthermore, chemokine signaling pathway and cytokine-cytokine receptor interaction were most probably involved in the development of UL. CONCLUSION: In conclusion, our study observed that a set of aberrantly expressed genes and the related biochemical pathways may lead to transformation of normal myometrium in pathological focuses.

A general regression framework for group testing data, which incorporates pool dilution effects.

Group testing, through the use of pooling, has been widely implemented as a more efficient means to screen individuals for infectious diseases. Typically, in these settings, practitioners are tasked with the complimentary goals of both case identification and estimation. For these purposes, many group testing strategies have been proposed, which address issues such as preserving anonymity in estimation studies, quality control, and classification. In general, these strategies require that a significant number of the individuals be retested, either in pools or individually. In order to provide practitioners with a general methodology that can be used to accurately and precisely analyze data of this form, herein, we propose a binary regression framework that can incorporate data arising from any group testing strategy. Further, we relax previously made assumptions regarding testing error rates by relating the diagnostic testing results to the latent biological marker levels of the individuals being tested. We investigate the finite sample performance of our proposed methodology through simulation and by applying our techniques to hepatitis B data collected as part of a study involving Irish prisoners.

Axonal regeneration in early stages of sciatic nerve crush injury is enhanced by α7nAChR in rats.

This study investigated the role of alpha 7 nicotinic acetylcholine receptor (α7nAChR) in axonal regeneration after crush injury to the rat sciatic nerve. The time course of α7nAChR expression following injury was assessed by immunohistochemistry and western blotting, and local inflammation, as indicated by the expression of tumor necrosis factor (TNF)-α, was detected by enzyme-linked immunosorbent assay. Axonal regeneration was evaluated by the pinch-test, morphometric analysis, and by measuring growth-associated protein 43 expressions. Local α7nAChR expression increased on day 1, peaked on day 3, and remained elevated on day 5 following nerve injuries. Prominent α7nAChR immunoreactivity was observed in Schwann cells, endothelial cells of the capillaries, and a small number of inflammatory cells. Application of the selective α7nAChR agonist PNU-282987 decreased TNF-α level and enhanced axonal regeneration, but this effect was blocked by concomitant treatment with methyllycaconitine, a α7nAChR antagonist. The results indicate that the local expression of α7nAChR is increased during the early stages of sciatic nerve injury, and application of a α7nAChR agonist promotes axonal regeneration by suppression of TNF-α-mediated inflammation. The α7nAChR can act as a neuroprotective agent and α7nAChR activation may be a useful therapeutic strategy to treat peripheral nerve injury.

A crucial role of IL-17 in bone resorption during rejection of fresh bone xenotransplantation in rats.

Bone grafting is a very useful approach to reconstruction of skeletal defects. However, the clinical use of autografts, allografts, and synthetic products is associated with a number of problems. The use of bone xenotransplantation, on the other hand, is associated with strong immune response, and therefore clear understanding of the mechanisms of immune rejection is essential. In this study, we used rabbit-to-rat xenotransplantation model to investigate the role of IL-17, and the relationship between IL-17, IL-23 and RANKL in inflammatory response during the bone grafting. Rabbit hindlimb bone was transplanted to rats, and half of the xenograft recipient animals received injection of IL-17 neutralizing antibodies before xenotransplantation. Sham control rats did not receive bone transplants. In the xenotransplant group, significant mononuclear cell infiltration and erosion/resorption of graft bone were observed. Administration of IL-17 neutralizing antibodies decreased mononuclear cell infiltration and inhibited bone resorption. The levels of IL-17+, IL-23+, and RANKL+ cells were elevated in xenotransplanted group from compared to the sham control. IL-17+ and RANKL+ cells infiltration was decreased upon administration of IL-17 neutralizing antibodies. No significant difference in the level of IL-23 in xenotransplanted groups with and without IL-17 antibodies was observed. Our results indicate that RANKL, IL-17, and IL-23 participate in the immune rejection of bone xenotransplantion. The IL-17/RANKL pathway may play a very important role in the bone resorption during rejection of fresh bone xenotransplants.