Deep Boosting Learning: A Brand-New Cooperative Approach for Image-Text Matching.

Image-text matching remains a challenging task due to heterogeneous semantic diversity across modalities and insufficient distance separability within triplets. Different from previous approaches focusing on enhancing multi-modal representations or exploiting cross-modal correspondence for more accurate retrieval, in this paper we aim to leverage the knowledge transfer between peer branches in a boosting manner to seek a more powerful matching model. Specifically, we propose a brand-new Deep Boosting Learning (DBL) algorithm, where an anchor branch is first trained to provide insights into the data properties, with a target branch gaining more advanced knowledge to develop optimal features and distance metrics. Concretely, an anchor branch initially learns the absolute or relative distance between positive and negative pairs, providing a foundational understanding of the particular network and data distribution. Building upon this knowledge, a target branch is concurrently tasked with more adaptive margin constraints to further enlarge the relative distance between matched and unmatched samples. Extensive experiments validate that our DBL can achieve impressive and consistent improvements based on various recent state-of-the-art models in the image-text matching field, and outperform related popular cooperative strategies, e.g., Conventional Distillation, Mutual Learning, and Contrastive Learning. Beyond the above, we confirm that DBL can be seamlessly integrated into their training scenarios and achieve superior performance under the same computational costs, demonstrating the flexibility and broad applicability of our proposed method.

Comparison of the impact of team-based learning and lecture-based learning on nursing students' core competencies: A systematic review and meta-analysis.

AIM: This study aims to evaluate the effect of team-based learning on the core competence of nursing students compared with traditional teaching methods. BACKGROUND: In recent years, team-based learning has been widely used as a learning and teaching method in the world. Not only the necessary knowledge, skills and attitudes, but also the core competence is necessary to cope with various clinical situations for nursing students. However, the effect of this new teaching method on core competence of nursing students is not consistent. DESIGN: The study was designed according to the preferred reporting entries guidelines statement for systematic reviews and meta-analyses and population, intervention, comparison, outcome and study. METHODS: Data were collected from PubMed, Embase, Web of Science, ScienceDirect and Scopus. The quality of studies was assessed using "The Newcastle Ottawa scale". A random-effect model of meta-analyses was conducted to generate pooled standardized mean differences (SMD) for core competence using Rev Man 5.4.1 software and STATASE 15. Moreover, subgroup, heterogeneity, sensitivity and publication bias analyses were conducted. RESULTS: A total of 14 articles with 1942 participants were included in the meta-analysis. Compared with the traditional pedagogy among nursing students, team-based learning pedagogy significantly increased theoretical performance, professional effects (self-directed learning ability and communication ability) but did not affect practice skills. In addition, one study found that learning attitudes were not improved in students with high or low academic performance. This might mean that the teaching model should be implemented for a long time, which essentially changed students' learning attitudes to improve students' self-directed learning ability and core competence, especially for students with low scores. CONCLUSIONS: In summary, findings indicated that team-based learning pedagogical approaches might be beneficial to improve teaching quality in nursing education. However, practice skills might not be sensitive to team-based learning because of the seriation of the original course. Nursing educators need to explore teaching strategies to cultivate high-quality nursing talents to cultivate nursing students with core competence and ensure that they are successfully qualified for new employment.

Unsupervised Domain Adaptation Using Fourier Phase Enhanced Training Images for Liver Tumors Detection in Multi-phase CT Images.

Computer-aided diagnostic methods, such as automatic and precise liver tumor detection, have a significant impact on healthcare. In recent years, deep learning-based liver tumor detection methods in multi-phase computed tomography (CT) images have achieved noticeable performance. Deep learning frameworks require a substantial amount of annotated training data but obtaining enough training data with high quality annotations is a major issue in medical imaging. Additionally, deep learning frameworks experience domain shift problems when they are trained using one dataset (source domain) and applied to new test data (target domain). To address the lack of training data and domain shift issues in multiphase CT images, here, we present an adversarial learning-based strategy to mitigate the domain gap across different phases of multiphase CT scans. We introduce to use Fourier phase component of CT images in order to improve the semantic information and more reliably identify the tumor tissues. Our approach eliminates the requirement for distinct annotations for each phase of CT scans. The experiment results show that our proposed method performs noticeably better than conventional training and other methods.

HMGB2 upregulation promotes the progression of hepatocellular carcinoma cells through the activation of ZEB1/vimentin axis.

Background: High mobility group box 2 (HMGB2) is abnormally expressed in human cancers and participated in multiple biological behaviors, such as proliferation, invasion and prognosis. However, its role in hepatocellular carcinoma (HCC) is largely unknown. Methods: In clinical sample analysis, 62 HCC patients were enrolled in this study. The expression of HMGB2 was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical method, clinical prognosis data were analyzed by Kaplan-Meier analysis. In cellular and molecular biology experiments, HMGB2 expression was analyzed in HCC cells. HMGB2 knockdown model was constructed by small interfering RNA (siRNA). Cell counting kit-8 (CCK-8) and cell migration & invasion assay were used to evaluate cell proliferative potential and motility. Recombinant human vimentin protein was used to partially restore the expression and function of vimentin. Western blot and immunochemical staining were performed to detect HMGB2 protein, zinc finger E-box binding homeobox 1 (ZEB1) and vimentin. Flow cytometry analyses were performed to determine the alteration of cell cycle in different groups. Results: HMGB2 was abnormally overexpressed in HCC. HMGB2 knockdown reduced malignant behaviors especially the proliferative potential and motility of HCC cells. The inhibition of HCC cells proliferation and mobility could be partially restored via treatment with recombinant vimentin protein. Our findings confirmed abnormal activation of HMGB2-ZEB1 vimentin axis facilitates HCC malignant proliferation and motility. The elevated HMGB2 expression in clinical samples was related to postoperative survival time of HCC patients. It indicated HMGB2 promotes the proliferation and motility potential of HCC via HMGB2-ZEB1-vimentin axis activation. Conclusions: HMGB2 is up-regulated in HCC and affects the malignant transformation by modulating HMGB2-ZEB1-vimentin signaling pathway, which may provide a research basis for evaluating the disease progression and developing clinical treatment strategies of HCC.

Effect of physical exercise on sleep quality in college students: Mediating role of smartphone use.

OBJECTIVE: To investigate the effect of physical exercise on sleep quality and the mediating effect of smartphone use behavior in college students. METHODS: A cross-sectional study design was adopted. An online survey of 5,075 college students was conducted using the Physical Activity Rating Scale-3, the Pittsburgh Sleep Quality Index, and the Mobile Phone Addiction Tendency Scale. RESULTS: The sleep quality of college students was poor, and the proportion of college students with good sleep quality was 23.567%. A significant correlation existed between sleep quality and physical exercise (r = -0.159, P < 0.001) and mobile phone addiction (r = 0.355, P < 0.001). Physical exercise can predict sleep quality in college students (ß = -0.011, P < 0.001). Smartphone use plays a part in mediating the process by which physical exercise affects sleep quality. CONCLUSION: Chinese college students have poor sleep quality. Physical exercise and smartphone use behavior are important factors affecting the sleep quality of college students. Physical exercise can directly predict the sleep quality of college students and can predict the sleep quality of college students through the mediating effect of smartphone use behavior.

Environmental and occupational exposure to cadmium associated with male reproductive health risk: a systematic review and meta-analysis based on epidemiological evidence.

There is an abundance of epidemiological evidence and animal experiments concerning the correlation between cadmium exposure and adverse male reproductive health outcomes. However, the evidence remains inconclusive. We conducted a literature search from PubMed, Embase, and Web of Science over the past 3 decades. Pooled r and 95% confidence intervals (CIs) were derived from Cd levels of the type of biological materials and different outcome indicators to address the large heterogeneity of existing literature. Cd was negatively correlated with semen parameters (r = - 0.122, 95% CI - 0.151 to - 0.092) and positively correlated with sera sex hormones (r = 0.104, 95% CI 0.060 to 0.147). Among them, Cd in three different biological materials (blood, semen, and urine) was negatively correlated with semen parameters, while among sex hormones, only blood and urine were statistically positively correlated. In subgroup analysis, blood Cd was negatively correlated with semen density, sperm motility, sperm morphology, and sperm count. Semen Cd was negatively correlated with semen concentration. As for serum sex hormones, blood Cd had no statistical significance with three hormones, while semen Cd was negatively correlated with testosterone. In summary, cadmium exposure might be associated with the risk of a decline in sperm quality and abnormal levels of sex hormones.

High-Performance Transformer Tracking.

Correlation has a critical role in the tracking field, especially in recent popular Siamese-based trackers. The correlation operation is a simple fusion method that considers the similarity between the template and the search region. However, the correlation operation is a local linear matching process, losing semantic information and easily falling into a local optimum, which may be the bottleneck in designing high-accuracy tracking algorithms. In this work, to determine whether a better feature fusion method exists than correlation, a novel attention-based feature fusion network, inspired by the transformer, is presented. This network effectively combines the template and search region features using attention mechanism. Specifically, the proposed method includes an ego-context augment module based on self-attention and a cross-feature augment module based on cross-attention. First, we present a transformer tracking (named TransT) method based on the Siamese-like feature extraction backbone, the designed attention-based fusion mechanism, and the classification and regression heads. Based on the TransT baseline, we also design a segmentation branch to generate the accurate mask. Finally, we propose a stronger version of TransT by extending it with a multi-template scheme and an IoU prediction head, named TransT-M. Experiments show that our TransT and TransT-M methods achieve promising results on seven popular benchmarks. Code and models are available at https://github.com/chenxin-dlut/TransT-M.

Plug-and-Play Regulators for Image-Text Matching.

Exploiting fine-grained correspondence and visual-semantic alignments has shown great potential in image-text matching. Generally, recent approaches first employ a cross-modal attention unit to capture latent region-word interactions, and then integrate all the alignments to obtain the final similarity. However, most of them adopt one-time forward association or aggregation strategies with complex architectures or additional information, while ignoring the regulation ability of network feedback. In this paper, we develop two simple but quite effective regulators which efficiently encode the message output to automatically contextualize and aggregate cross-modal representations. Specifically, we propose (i) a Recurrent Correspondence Regulator (RCR) which facilitates the cross-modal attention unit progressively with adaptive attention factors to capture more flexible correspondence, and (ii) a Recurrent Aggregation Regulator (RAR) which adjusts the aggregation weights repeatedly to increasingly emphasize important alignments and dilute unimportant ones. Besides, it is interesting that RCR and RAR are "plug-and-play": both of them can be incorporated into many frameworks based on cross-modal interaction to obtain significant benefits, and their cooperation achieves further improvements. Extensive experiments on MSCOCO and Flickr30K datasets validate that they can bring an impressive and consistent R@1 gain on multiple models, confirming the general effectiveness and generalization ability of the proposed methods.

Metavirome of 31 tick species provides a compendium of 1,801 RNA virus genomes.

The increasing prevalence and expanding distribution of tick-borne viruses globally have raised health concerns, but the full repertoire of the tick virome has not been assessed. We sequenced the meta-transcriptomes of 31 different tick species in the Ixodidae and Argasidae families from across mainland China, and identified 724 RNA viruses with distinctive virome compositions among genera. A total of 1,801 assembled and complete or nearly complete viral genomes revealed an extensive diversity of genome architectures of tick-associated viruses, highlighting ticks as a reservoir of RNA viruses. We examined the phylogenies of different virus families to investigate virome evolution and found that the most diverse tick-associated viruses are positive-strand RNA virus families that demonstrate more ancient divergence than other arboviruses. Tick-specific viruses are often associated with only a few tick species, whereas virus clades that can infect vertebrates are found in a wider range of tick species. We hypothesize that tick viruses can exhibit both 'specialist' and 'generalist' evolutionary trends. We hope that our virome dataset will enable much-needed research on vertebrate-pathogenic tick-associated viruses.

Acquired Hemophilia A: A Retrospective Multicenter Analysis of 42 Patients.

INTRODUCTION: Immunosuppressive therapy (IST) for acquired hemophilia A (AHA) results in remission within days to months in 60% to 80% of patients. However, little is known regarding the predictors of response. AIM: This study aimed to identify the factors that influence response to treatment. METHODS: The data of 42 patients with AHA from three hospitals were retrospectively analyzed. RESULTS: All 42 AHA patients received IST; complete treatment data were available for 34 patients. The response rate was 60% among the 5/34 (14.7%) patients who received steroids alone, 70.8% among the 24/34 (70.6%) patients who received steroids plus cyclophosphamide, and 80% among the 5/34 (14.7%) patients who received steroids plus cyclophosphamide and rituximab. Overall, 29/34 (85.3%) patients achieved CR; 4/34 (13.8%) of them relapsed after a median time of 410 (21-1279) days. Adverse events occurred in 14/34 (41.2%) patients: 13/34 (38.2%) had infections and 1/34 (2.9%) developed pancytopenia. In univariate and multivariate Cox regression analyses, FVIII inhibitor titer ≥20 BU/mL was the only significant prognostic factor affecting time to CR. No variable had significant effect on OS. CONCLUSION: FVIII inhibitory antibody titer ≥20 BU/mL appears to be an important predictor of time to complete response in patients with acquired hemophilia A treated with immunosuppressive therapy.

Unsupervised Domain Adaptation Using Adversarial Learning and Maximum Square Loss for Liver Tumors Detection in Multi-phase CT Images.

Automatic and efficient liver tumor detection in multi-phase CT images is essential in computer-aided diagnosis of liver tumors. Nowadays, deep learning has been widely used in medical applications. Normally, deep learning-based AI systems need a large quantity of training data, but in the medical field, acquiring sufficient training data with high-quality annotations is a significant challenge. To solve the lack of training data issue, domain adaptation-based methods have recently been developed as a technique to bridge the domain gap across datasets with different feature characteristics and data distributions. This paper presents a domain adaptation-based method for detecting liver tumors in multi-phase CT images. We adopt knowledge for model learning from PV phase images to ART and NC phase images. Clinical Relevance- To minimize the domain gap we employ an adversarial learning scheme with the maximum square loss for mid-level output feature maps using an anchorless detector. Experiments show that our proposed method performs much better for various CT-phase images than normal training.

Comprehensive Evaluation and Application of a Novel Method to Isolate Cell-Free DNA Derived From Bile of Biliary Tract Cancer Patients.

Cell-free DNA (cfDNA) exists in various types of bodily fluids, including plasma, urine, bile, and others. Bile cfDNA could serve as a promising liquid biopsy for biliary tract cancer (BTC) patients, as bile directly contacts tumors in the biliary tract system. However, there is no commercial kit or widely acknowledged method for bile cfDNA extraction. In this study, we established a silica-membrane-based method, namely 3D-BCF, for bile cfDNA isolation, exhibiting effective recovery of DNA fragments in the spike-in assay. We then compared the 3D-BCF method with four other commercial kits: the BIOG cfDNA Easy Kit (BIOG), QIAamp DNA Mini Kit (Qiagen), MagMAXTM Cell-Free DNA Isolation Kit (Thermo Fisher), and NORGEN Urine Cell-Free Circulating DNA Purification Mini Kit (Norgen Biotek). The proposed 3D-BCF method exhibited the highest cfDNA isolation efficiency (p < 0.0001) from patient bile samples, and bile cfDNA of short, medium or long fragments could all be extracted effectively. To test whether the extracted bile cfDNA from patients carries tumor-related genomic information, we performed next-generation sequencing on the cfDNA and verified the gene-mutation results by polymerase chain reaction (PCR)-Sanger chromatograms and copy-number-variation (CNV) detection by fluorescence in situ hybridization (FISH) of tumor tissues. The 3D-BCF method could efficiently extract cfDNA from bile samples, providing technical support for bile cfDNA as a promising liquid biopsy for BTC patient diagnosis and prognosis.

HMGCS2 silencing attenuates high glucose-induced in vitro diabetic cardiomyopathy by increasing cell viability, and inhibiting apoptosis, inflammation, and oxidative stress.

Diabetic cardiomyopathy (DCM) is a diabetic mellitus-related complications and progression of DCM may eventually lead to heart failure, while mechanisms related to DCM pathophysiology remain unclear. The study was undertaken to identify possible hub genes associated with DCM progression through bioinformatics analysis and to validate the role of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) in DCM progression using a cellular model of high glucose (HG)-induced DCM. The common differentially expressed genes (DEGs) between GSE173884 and GSE161827 were used for PPI network analysis. Our results identified 17 common DEGs between GSE173384 and GSE161827. Further analysis of the protein-protein interaction network identified nine hub genes and HMGCS2. The in vitro functional assays showed that HG induced up-regulation of HMGCS2, suppressed cardiomyocyte viability, enhanced apoptosis, inflammation, and oxidative stress of cardiomyocytes. Gain-of-function assays showed that HMGCS2 overexpression reduced cell viability, increased apoptosis, caspase-3/-9 activity, up-regulated interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α (TNF-α) expression, decreased superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase expression, increased malondialdehyde (MDA) content, and reactive oxygen species (ROS) level but inhibited total antioxidant activity, SOD activity, CAT activity, and glutathione content in cardiomyocytes. Rescue experiments demonstrated HMGCS2 silence attenuated HG-induced decrease in cardiomyocyte viability and increase in cardiomyocyte apoptosis, inflammation, and oxidative stress. All in all, our study identified HMGCS2 as a hub gene in DCM pathophysiology and further functional studies indicated that HMGCS2 may aggravate DCM progression by reducing cardiomyocyte viability, increasing cardiomyocyte apoptosis, and promoting inflammation and oxidative stress in cardiomyocytes.

Molecular Detection of Novel Borrelia Species, Candidatus Borrelia javanense, in Amblyomma javanense Ticks from Pangolins.

A novel Borrelia species, Candidatus Borrelia javanense, was found in ectoparasite ticks, Amblyomma javanense, from Manis javanica pangolins seized in anti-smuggling operations in southern China. Overall, 12 tick samples in 227 (overall prevalence 5.3%) were positive for Candidatus B. javanense, 9 (5.1%) in 176 males, and 3 (5.9%) in 51 females. The phylogenetic analysis, based on the 16S rRNA gene and the flagellin gene sequences of the Borrelia sp., exhibited strong evidence that Candidatus B. javanense did not belong to the Lyme disease Borrelia group and the relapsing fever Borrelia group but another lineage of Borrelia. The discovery of the novel Borrelia species suggests that A. javanense may be the transmit vector, and the M. javanica pangolins should be considered a possible origin reservoir in the natural circulation of these new pathogens. To our knowledge, this is the first identification of a novel Borrelia species agent in A. javanense from pangolins. Whether the novel agent is pathogenic to humans is unknown and needs further research.

Non-invasive detection of biliary tract cancer by low-coverage whole genome sequencing from plasma cell-free DNA: A prospective cohort study.

BACKGROUND: The diagnosis of biliary tract cancer (BTC) is challenging in clinical practice. We performed a prospective study to evaluate the value of plasma copy number variation (CNV) assays in diagnosing BTC. METHODS: 47 treatment-naïve patients with suspicious biliary lesions were recruited. Plasma samples were collected at admission. Cell-free DNA was analyzed by low coverage whole genome sequencing, followed by CNV analyses via a customized bioinformatics workflow, namely the ultrasensitive chromosomal aneuploidy detector. RESULTS: 29 patients were pathologically diagnosed as BTC, including 8 gallbladder cancers (GBCs) and 21 cholangiocarcinomas (CCs). Cancer patients had more CNV signals as compared with benign patients (26/29 vs. 2/18, P < 0.001). The most frequent copy number gains were chr3q (7/29) and chr8q (6/29). The most frequent copy number losses were chr7p (6/29), chr17p (6/29), and chr19p (6/29). The sensitivity and specificity of plasma CNV assays in diagnosing BTC were 89.7% and 88.9%, respectively. For CA 19-9 (cutoff: 37 U/ml), the sensitivity was 58.6% and the specificity was 72.2%. The diagnostic accuracy of CNV assays significantly outperformed CA 19-9 (AUC 0.91 vs. 0.62, P = 0.004). Compared with CA 19-9 alone, the adding of CNV profiles to CA 19-9 increased the sensitivity in diagnosing GBC (75.0% vs. 25.0%) and CC (100% vs. 52.4%). Higher CNV burden was also associated with decreased overall survival (Hazard ratio = 4.32, 95% CI 2.06-9.08, P = 0.033). DISCUSSION: Our results suggest that BTC harbors rich plasma CNV signals, and their assays might be useful for diagnosing BTC.

Environmental Policy Integration in the Energy Sector of China: The Roles of the Institutional Context.

The rapid growth of China's renewable energy market and production capacity has attracted worldwide attention. Environmental policy integration in the energy sector and the institutional background behind this growth have seen little examination. In this paper, we present an assessment of environmental policy integration (EPI), attempting to reveal how the institutional factors facilitate EPI in the energy sector of China. A qualitative analytical framework involving normative, organizational, and procedural dimensions, incorporating multiple pieces of quantitative evidence, was applied. The results show that an ambitious and long-term normative vision covering political will, social backing, and cultural foundation in China is indispensable to the EPI process in the energy sector. The energy agency's trans-sector cooperation in policy-making has been established to overcome the sectoral compartmentalization. China's EPI in energy has a relatively complete and stable regulating system but, at the same time, it is expected to obtain more benefits from market cultivation and public participation. In this process, advantages such as the co-evolution of the green energy innovation, market, and society do exist; however, this market-oriented approach may bring the risk of economic and societal disturbances when interest-driven production capacity growth far surpasses market and societal requirements. This potential risk needs to be handled and prevented by strong governmental guidance and support. The continuous ambitious and long-term visioning of EPI, sufficient governmental funds, and a proactive industrial plan for renewable energy, are suggested.

Large-Scale Comparative Analyses of Tick Genomes Elucidate Their Genetic Diversity and Vector Capacities.

Among arthropod vectors, ticks transmit the most diverse human and animal pathogens, leading to an increasing number of new challenges worldwide. Here we sequenced and assembled high-quality genomes of six ixodid tick species and further resequenced 678 tick specimens to understand three key aspects of ticks: genetic diversity, population structure, and pathogen distribution. We explored the genetic basis common to ticks, including heme and hemoglobin digestion, iron metabolism, and reactive oxygen species, and unveiled for the first time that genetic structure and pathogen composition in different tick species are mainly shaped by ecological and geographic factors. We further identified species-specific determinants associated with different host ranges, life cycles, and distributions. The findings of this study are an invaluable resource for research and control of ticks and tick-borne diseases.

Genetic Diversity and Coexistence of Babesia in Ticks (Acari: Ixodidae) from Northeastern China.

Background: Human babesiosis is an emerging zoonotic disease transmitted by ticks in China. A few systematic reports on Babesia spp. was involved with ticks, especially in the human babesiosis endemic areas in Northeastern China. Materials and Methods: Ticks were collected from 30 individual waypoints along 2.0 km transects in two recreational forests. Babesia spp. infection in ticks was screened by amplifying the partial 18s rRNA gene with subsequent sequencing. Multivariate logistic regression analysis was used to determine the association between tick infection and related environmental risk factors. Cluster analyses were performed using SaTScan v6.0 software to identify any geographical cluster of infected ticks. Results: A total of 2380 Ixodes persulcatus and 461 Haemaphysalis concinna ticks were collected. Of the 0.97% of I. persulcatus ticks that tested positive, five Babesia species were identified, including B. bigemina (n = 6), B. divergens (n = 2), B. microti (n = 3), B. venatorum (n = 11), and one novel strain HLJ-8. Thirteen (2.92%) H. concinna ticks tested positive for B. bigemina (n = 1), B. divergens (n = 1), three genetic variants of Babesia represented by HLJ-874, which was closely related to Babesia sp.MA#361-1, and eight other Babesia variants represented by HLJ242, which were similar to B. crassa. Each study site had 5-6 different Babesia spp. One waypoint was more likely to yield B. venatorum (relative risk = 15.36, p = 0.045) than all other waypoints. Conclusions: There exists a high genetic diversity of Babesia spp. across a relatively small sampled region. Further study is needed to understand the risks these variants pose to human health.

Upregulation of TRPC6 Mediated by PAX6 Hypomethylation Is Involved in the Mechanical Allodynia Induced by Chemotherapeutics in Dorsal Root Ganglion.

BACKGROUND: Although the action mechanism of antineoplastic agents is different, oxaliplatin, paclitaxel, or bortezomib as first-line antineoplastic drugs can induce painful neuropathy. In rodents, mechanical allodynia is a common phenotype of painful neuropathy for 3 chemotherapeutics. However, whether there is a common molecular involved in the different chemotherapeutics-induced painful peripheral neuropathy remains unclear. METHODS: Mechanical allodynia was tested by von Frey hairs following i.p. injection of vehicle, oxaliplatin, paclitaxel, or bortezomib in Sprague-Dawley rats. Reduced representation bisulfite sequencing and methylated DNA immunoprecipitation were used to detect the change of DNA methylation. Western blot, quantitative polymerase chain reaction, chromatin immunoprecipitation, and immunohistochemistry were employed to explore the molecular mechanisms. RESULTS: In 3 chemotherapeutic models, oxaliplatin, paclitaxel, or bortezomib accordantly upregulated the expression of transient receptor potential cation channel, subfamily C6 (TRPC6) mRNA and protein without affecting the DNA methylation level of TRPC6 gene in DRG. Inhibition of TRPC6 by using TRPC6 siRNA (i.t., 10 consecutive days) relieved mechanical allodynia significantly following application of chemotherapeutics. Furthermore, the downregulated recruitment of DNA methyltransferase 3 beta (DNMT3b) at paired box protein 6 (PAX6) gene led to the hypomethylation of PAX6 gene and increased PAX6 expression. Finally, the increased PAX6 via binding to the TPRC6 promoter contributes to the TRPC6 increase and mechanical allodynia following chemotherapeutics treatment. CONCLUSIONS: The TRPC6 upregulation through DNMT3b-mediated PAX6 gene hypomethylation participated in mechanical allodynia following application of different chemotherapeutic drugs.

In Situ Raman Monitoring and Manipulating of Interfacial Hydrogen Spillover by Precise Fabrication of Au/TiO2 /Pt Sandwich Structures.

The spillover of hydrogen species and its role in tuning the activity and selectivity in catalytic hydrogenation have been investigated in situ using surface-enhanced Raman spectroscopy (SERS) with 10 nm spatial resolution through the precise fabrication of Au/TiO2 /Pt sandwich nanostructures. In situ SERS study reveals that hydrogen species can efficiently spillover at Pt-TiO2 -Au interfaces, and the ultimate spillover distance on TiO2 is about 50 nm. Combining kinetic isotope experiments and density functional theory calculations, it is found that the hydrogen spillover proceeds via the water-assisted cleavage and formation of surface hydrogen-oxygen bond. More importantly, the selectivity in the hydrogenation of the nitro or isocyanide group is manipulated by controlling the hydrogen spillover. This work provides molecular insights to deepen the understanding of hydrogen activation and boosts the design of active and selective catalysts for hydrogenation.