Knowledge mapping and research trends of exosomes in pancreatic cancer: a bibliometric analysis and review (2013-2023).

Objective: This review aims to provide a quantitative and qualitative bibliometric analysis of literature from 2013 to 2023 on the role of exosomes in PC, with the goal of identifying current trends and predicting future hotspots. Methods: We retrieved relevant publications concerning exosomes in PC, published between 2013 and 2023, from the Web of Science Core Collection. Bibliometric analyses were conducted using VOSviewer(1.6.19), CiteSpace(6.2.R4), and Microsoft Excel (2019). Results: A total of 624 papers were analyzed, authored by 4017 researchers from 55 countries/regions and 855 institutions, published in 258 academic journals. China (n=285, 34.42%) and the United States (n=183, 24.87%) were the most frequent contributors and collaborated closely. However, publications from China had a relatively low average number of citations (41.45 times per paper). The output of Shanghai Jiao Tong University ranked first, with 28 papers (accounting for 4.5% of the total publications). Cancers (n=31, 4.9%); published the most papers in this field. Researcher Margot Zoeller published the most papers (n=12) on this topic. Research hotspots mainly focused on the mechanisms of exosomes in PC onset and progression, the role of exosomes in PC early diagnosis and prognosis, exosomes promote the development of PC chemoresistance, and potential applications of exosomes as drug carriers for PC therapies. We observed a shift in research trends, from mechanistic studies toward clinical trials, suggesting that clinical applications will be the focus of future attention. Emerging topics were pancreatic stellate cells, diagnostic biomarkers, mesenchymal stem cells, extracellular vesicles. Conclusion: Our scientometric and visual analysis provides a comprehensive overview of the literature on the role of exosomes in PC published during 2013-2023. This review identifies the frontiers and future directions in this area over the past decade, and is expected to provide a useful reference for researchers in this field.

MF-Net: multi-scale feature extraction-integration network for unsupervised deformable registration.

Deformable registration plays a fundamental and crucial role in scenarios such as surgical navigation and image-assisted analysis. While deformable registration methods based on unsupervised learning have shown remarkable success in predicting displacement fields with high accuracy, many existing registration networks are limited by the lack of multi-scale analysis, restricting comprehensive utilization of global and local features in the images. To address this limitation, we propose a novel registration network called multi-scale feature extraction-integration network (MF-Net). First, we propose a multiscale analysis strategy that enables the model to capture global and local semantic information in the image, thus facilitating accurate texture and detail registration. Additionally, we introduce grouped gated inception block (GI-Block) as the basic unit of the feature extractor, enabling the feature extractor to selectively extract quantitative features from images at various resolutions. Comparative experiments demonstrate the superior accuracy of our approach over existing methods.

TMC7 functions as a suppressor of Piezo2 in primary sensory neurons blunting peripheral mechanotransduction.

The transmembrane channel-like (TMC) protein family comprises eight members, with TMC1 and TMC2 being extensively studied. This study demonstrates substantial co-expression of TMC7 with the mechanosensitive channel Piezo2 in somatosensory neurons. Genetic deletion of TMC7 in primary sensory ganglia neurons in vivo enhances sensitivity in both physiological and pathological mechanosensory transduction. This deletion leads to an increase in proportion of rapidly adapting (RA) currents conducted by Piezo2 in dorsal root ganglion (DRG) neurons and accelerates RA deactivation kinetics. In HEK293 cells expressing both proteins, TMC7 significantly suppresses the current amplitudes of co-expressed Piezo2. Our findings reveal that TMC7 and Piezo2 exhibit physical interactions, and both proteins also physically interact with cytoskeletal ß-actin. We hypothesize that TMC7 functions as an inhibitory modulator of Piezo2 in DRG neurons, either through direct inhibition or by disrupting the transmission of mechanical forces from the cytoskeleton to the channel.

Investigating potential biomarkers of acute pancreatitis in patients with a BMI>30 using Mendelian randomization and transcriptomic analysis.

BACKGROUND: Acute pancreatitis (AP) has become a significant global health concern, and a high body mass index (BMI) has been identified as a key risk factor exacerbating this condition. Within this context, lipid metabolism assumes a critical role. The complex relationship between elevated BMI and AP, mediated by lipid metabolism, markedly increases the risk of complications and mortality. This study aimed to accurately define the correlation between BMI and AP, incorporating a comprehensive analysis of the interactions between individuals with high BMI and AP. METHODS: Mendelian randomization (MR) analysis was first applied to determine the causal relationship between BMI and the risk of AP. Subsequently, three microarray datasets were obtained from the GEO database. This was followed by an analysis of differentially expressed genes and the application of weighted gene coexpression network analysis (WGCNA) to identify key modular genes associated with AP and elevated BMI. Functional enrichment analysis was then performed to shed light on disease pathogenesis. To identify the most informative genes, machine learning algorithms, including Random Forest (RF), Support Vector Machine-Recursive Feature Elimination (SVM-RFE), and Least Absolute Shrinkage and Selection Operator (LASSO), were employed. Subsequent analysis focused on the colocalization of the Quantitative Trait Loci (eQTL) data associated with the selected genes and Genome-Wide Association Studies (GWAS) data related to the disease. Preliminary verification of gene expression trends was conducted using external GEO datasets. Ultimately, the diagnostic potential of these genes was further confirmed through the development of an AP model in mice with a high BMI. RESULTS: A total of 21 intersecting genes related to BMI>30, AP, and lipid metabolism were identified from the datasets. These genes were primarily enriched in pathways related to cytosolic DNA sensing, cytokine‒cytokine receptor interactions, and various immune and inflammatory responses. Next, three machine learning techniques were utilized to identify HADH as the most prevalent diagnostic gene. Colocalization analysis revealed that HADH significantly influenced the risk factors associated with BMI and AP. Furthermore, the trend in HADH expression within the external validation dataset aligned with the trend in the experimental data, thus providing a preliminary validation of the experimental findings.The changes in its expression were further validated using external datasets and quantitative real-time polymerase chain reaction (qPCR). CONCLUSION: This study systematically identified HADH as a potential lipid metabolism-grounded biomarker for AP in patients with a BMI>30.

N-Heterocyclic Carbene-Catalyzed Formal Intramolecular [3 + 2] Annulations of Cyclohexadienone-Tethered Ynals.

A formal [3 + 2] annulation of cyclohexadienone-tethered ynals is enabled by an N-heterocyclic carbene (NHC) catalyst, affording a tricyclo[6.2.1.04,11]undecane framework. This study represents the first demonstration of using C═C double bonds as the reaction partner in the NHC-catalyzed annulation of ynals. This strategy is characterized by mild reaction conditions and 100% atom economy as well as high catalytic performance and efficiency.

The transmembrane channel-like 6 (TMC6) in primary sensory neurons involving thermal sensation via modulating M channels.

Introduction: The transmembrane channel-like (TMC) protein family contains eight members, TMC1-TMC8. Among these members, only TMC1 and TMC2 have been intensively studied. They are expressed in cochlear hair cells and are crucial for auditory sensations. TMC6 and TMC8 contribute to epidermodysplasia verruciformis, and predispose individuals to human papilloma virus. However, the impact of TMC on peripheral sensation pain has not been previously investigated. Methods: RNAscope was employed to detect the distribution of TMC6 mRNA in DRG neurons. Electrophysiological recordings were conducted to investigate the effects of TMC6 on neuronal characteristics and M channel activity. Zn2+ indicators were utilized to detect the zinc concentration in DRG tissues and dissociated neurons. A series of behavioural tests were performed to assess thermal and mechanical sensation in mice under both physiological and pathological conditions. Results and Discussion: We demonstrated that TMC6 is mainly expressed in small and medium dorsal root ganglion (DRG) neurons and is involved in peripheral heat nociception. Deletion of TMC6 in DRG neurons hyperpolarizes the resting membrane potential and inhibits neuronal excitability. Additionally, the function of the M channel is enhanced in TMC6 deletion DRG neurons owing to the increased quantity of free zinc in neurons. Indeed, heat and mechanical hyperalgesia in chronic pain are alleviated in TMC6 knockout mice, particularly in the case of heat hyperalgesia. This suggests that TMC6 in the small and medium DRG neurons may be a potential target for chronic pain treatment.

3D-CAM: a novel context-aware feature extraction framework for neurological disease classification.

In clinical practice and research, the classification and diagnosis of neurological diseases such as Parkinson's Disease (PD) and Multiple System Atrophy (MSA) have long posed a significant challenge. Currently, deep learning, as a cutting-edge technology, has demonstrated immense potential in computer-aided diagnosis of PD and MSA. However, existing methods rely heavily on manually selecting key feature slices and segmenting regions of interest. This not only increases subjectivity and complexity in the classification process but also limits the model's comprehensive analysis of global data features. To address this issue, this paper proposes a novel 3D context-aware modeling framework, named 3D-CAM. It considers 3D contextual information based on an attention mechanism. The framework, utilizing a 2D slicing-based strategy, innovatively integrates a Contextual Information Module and a Location Filtering Module. The Contextual Information Module can be applied to feature maps at any layer, effectively combining features from adjacent slices and utilizing an attention mechanism to focus on crucial features. The Location Filtering Module, on the other hand, is employed in the post-processing phase to filter significant slice segments of classification features. By employing this method in the fully automated classification of PD and MSA, an accuracy of 85.71%, a recall rate of 86.36%, and a precision of 90.48% were achieved. These results not only demonstrates potential for clinical applications, but also provides a novel perspective for medical image diagnosis, thereby offering robust support for accurate diagnosis of neurological diseases.

Readily releasable ß cells with tight Ca2+-exocytosis coupling dictate biphasic glucose-stimulated insulin secretion.

Biphasic glucose-stimulated insulin secretion (GSIS) is essential for blood glucose regulation, but a mechanistic model incorporating the recently identified islet ß cell heterogeneity remains elusive. Here, we show that insulin secretion is spatially and dynamically heterogeneous across the islet. Using a zinc-based fluorophore with spinning-disc confocal microscopy, we reveal that approximately 40% of islet cells, which we call readily releasable ß cells (RRßs), are responsible for 80% of insulin exocytosis events. Although glucose up to 18.2 mM fully mobilized RRßs to release insulin synchronously (first phase), even higher glucose concentrations enhanced the sustained secretion from these cells (second phase). Release-incompetent ß cells show similarities to RRßs in glucose-evoked Ca2+ transients but exhibit Ca2+-exocytosis coupling deficiency. A decreased number of RRßs and their altered secretory ability are associated with impaired GSIS progression in ob/ob mice. Our data reveal functional heterogeneity at the level of exocytosis among ß cells and identify RRßs as a subpopulation of ß cells that make a disproportionally large contribution to biphasic GSIS from mouse islets.

Photo-Controllable Smart Hydrogels for Biomedical Application: A Review.

Nowadays, smart hydrogels are being widely studied by researchers because of their advantages such as simple preparation, stable performance, response to external stimuli, and easy control of response behavior. Photo-controllable smart hydrogels (PCHs) are a class of responsive hydrogels whose physical and chemical properties can be changed when stimulated by light at specific wavelengths. Since the light source is safe, clean, simple to operate, and easy to control, PCHs have broad application prospects in the biomedical field. Therefore, this review timely summarizes the latest progress in the PCHs field, with an emphasis on the design principles of typical PCHs and their multiple biomedical applications in tissue regeneration, tumor therapy, antibacterial therapy, diseases diagnosis and monitoring, etc. Meanwhile, the challenges and perspectives of widespread practical implementation of PCHs are presented in biomedical applications. This study hopes that PCHs will flourish in the biomedical field and this review will provide useful information for interested researchers.

Association of non-HDL-C and depression: a cross-sectional analysis of the NHANES data.

Objectives: Non-high-density lipoprotein cholesterol (non-HDL-C) has attracted attention because it is associated with a variety of diseases and is easy to measure. However, the relationship between non-HDL-C and depression is still unclear. Our aim was to assess the relationship between non-HDL-C and depression using the cross-sectional NHANES survey from 2005 to 2018. Methods: We examined the association between non-HDL-C and depression using weighted multivariable logistic regression models and subgroup analysis. Sensitivity analysis demonstrated the robustness of the results. Results: There were 42,143 participants in this study and 8.6% had depression (weighted 7.53%). Non-HDL-C was higher in participants with depression compared to those without depression (weighted mean 3.64 vs. 3.73, p < 0.01). There was a positive association between non-HDL-C and depression with a 95% OR of 1.22 adjusted for multifactorial (95% CI,1.03-1.45). In subgroup analyses, non-HDL-C was positively associated with depression in men (OR, 1.31; 95% CI, 1.01-1.70), normal BMI (OR: 0.93; 95% CI: 0.66-1.32) and in participants without hypertension (OR, 1.29; 95% CI, 1.01-1.66). Conclusion: Non-HDL-C positively correlated with depression, and further research may be better for clinical service.

Voltage-gated potassium channels KCNQs: Structures, mechanisms, and modulations.

KCNQ (Kv7) channels are voltage-gated, phosphatidylinositol 4,5-bisphosphate- (PIP2-) modulated potassium channels that play essential roles in regulating the activity of neurons and cardiac myocytes. Hundreds of mutations in KCNQ channels are closely related to various cardiac and neurological disorders, such as long QT syndrome, epilepsy, and deafness, which makes KCNQ channels important drug targets. During the past several years, the application of single-particle cryo-electron microscopy (cryo-EM) technique in the structure determination of KCNQ channels has greatly advanced our understanding of their molecular mechanisms. In this review, we summarize the currently available structures of KCNQ channels, analyze their special voltage gating mechanism, and discuss their activation mechanisms by both the endogenous membrane lipid and the exogenous synthetic ligands. These structural studies of KCNQ channels will guide the development of drugs targeting KCNQ channels.

Association between adult attachment style, communication patterns and caregiver burden in parents of children with solid tumors: A cross-sectional study.

PURPOSE: The primary purpose of this cross-sectional study was to delve into the connections among adult attachment styles, communication patterns, and caregiver burden within the sample of parents caring for children diagnosed with solid tumors. METHODS: A sample of 456 parents responsible for the care of children with solid tumors was conveniently recruited from a pediatric oncology ward at a tertiary hospital from September 2021 to September 2022. The data collection process included a questionnaire on general information, the Caregiver Burden Inventory, the Adult Attachment Questionnaire Short Form, and the Communication Pattern Questionnaire. RESULTS: The findings demonstrated a strong and positive connection between caregiver burden and attachment avoidance, whereas no considerable association was observed for attachment anxiety. Attachment avoidance exhibited a positive link with communication patterns and caregiver burden, and a noteworthy inverse correlation with attachment anxiety. Additionally, communication patterns were uncovered as a mediator in the association between attachment avoidance and caregiver burden. CONCLUSIONS: This study underscores the role of communication patterns as mediators between attachment avoidance and caregiver burden among parents of children with solid tumors. These outcomes emphasize the significance of considering attachment styles and communication patterns when comprehending caregiver burden, and can guide the development of targeted interventions to provide support for parents within this challenging context.

[Human muscle fatigue monitoring method and its application for exoskeleton interactive control].

Aiming at the human-computer interaction problem during the movement of the rehabilitation exoskeleton robot, this paper proposes an adaptive human-computer interaction control method based on real-time monitoring of human muscle state. Considering the efficiency of patient health monitoring and rehabilitation training, a new fatigue assessment algorithm was proposed. The method fully combined the human neuromuscular model, and used the relationship between the model parameter changes and the muscle state to achieve the classification of muscle fatigue state on the premise of ensuring the accuracy of the fatigue trend. In order to ensure the safety of human-computer interaction, a variable impedance control algorithm with this algorithm as the supervision link was proposed. On the basis of not adding redundant sensors, the evaluation algorithm was used as the perceptual decision-making link of the control system to monitor the muscle state in real time and carry out the robot control of fault-tolerant mechanism decision-making, so as to achieve the purpose of improving wearing comfort and improving the efficiency of rehabilitation training. Experiments show that the proposed human-computer interaction control method is effective and universal, and has broad application prospects.

The future of robotic pancreaticoduodenal surgery: a bibliometric analysis.

OBJECTIVES: Robotic pancreaticoduodenectomy (RPD) has garnered significant research attention in the last decade. However, no bibliometric studies have been conducted on this field yet. Therefore, the aim of this study is to provide an up-to-date analysis of the current state of research, as well as future trends and hotspots in RPD, through a bibliometric analysis. MATERIALS AND METHODS: We conducted a thorough search of all literature related to RPD in the Web of Science Core Collection (WoSCC). We then analyzed this literature for a variety of factors, including authorship, country of origin, institutional affiliations, and keywords. To visualize our findings, we utilized Citespace 6.1.R3, which enabled us to create network visualization maps, perform cluster analysis, and extract burst words. RESULTS: A total of 264 articles were retrieved. Zureikat is the author with the largest contribution in this field, and Surgical Endoscopy and Other International Techniques is the journal with the largest number of papers in this field. The United States is the core research country in this field. The University of Pittsburgh is the most productive institution. According to the data, outcome, pancreas fistula, definition, risk factor, stay, survival, learning curve and experience are recognized as research hotspots in this field. CONCLUSIONS: This study is the first bibliometric study in the field of RPD. Our data will help us better understand the development trend of the field, and determine research hotspots and research directions. The research results provide practical information for other scholars to understand key directions and cutting-edge information.

Urban-Rural Disparities in Knowledge, Use and Perceived Benefits of Nutrition Labels in China: Evidence from 10 Provinces.

There exist significant gaps in nutritional status between urban and rural populations in China. The previous literature has shown that more knowledge and usage of nutrition labels are instrumental in improving diet quality and health. The aim of the study is to analyze: (1) Are there urban-rural disparities in consumer knowledge, use and perceived benefits of nutrition labels in China; (2) If so, what are the magnitudes of the disparities; (3) What can explain the disparities, and how can the disparities be reduced? The Oaxaca-Blinder (O-B) decomposition is utilized to analyze the predictors of urban-rural disparities in nutrition labels based on a self-conducted study of Chinese individuals. The information from a total of 1635 individuals (aged 11-81 years) across China in 2016 was collected in the survey. We find that rural respondents have less knowledge, lower usage and perceived benefits of nutrition labels than their urban counterparts. Demographics, focus on food safety, frequent shopping locations and income jointly explain 98.9% of the disparity in the knowledge of nutrition labels. Nutrition label knowledge is the predictor which contributes most to urban-rural disparity in label use-accounting for 29.6% of the disparity. Nutrition label knowledge and use are the two biggest predictors of disparities in perceived benefits-accounting for 29.7% and 22.8% of the disparity in perceived benefits, respectively. Our study suggests that policies aiming to improve income and education, as well as raising awareness of food safety in rural areas, are promising in closing the urban-rural disparities in nutrition labels knowledge, use, diet quality and health in China.

Enhancing the activity of disulfide-bond-containing proteins via promoting disulfide bond formation in Bacillus licheniformis.

Disulfide bonds in proteins have strongly influence on the folding efficiency by constraining the conformational space. The inefficient disulfide bond formation of proteins is the main limiting factor of enzyme activity and stability. This study aimed to increase the activity of disulfide-bond-containing proteins via promoting disulfide bonds formation in Bacillus licheniformis. Initially, the glutamate decarboxylase GAD from Escherichia coli was selected as the model protein and introduced into the B. licheniformis. Then, the disulfide isomerase and oxidoreductase from different sources were excavated and overexpressed successively to improve the catalytic efficiency of GAD. The final engineered B. licheniformis showed significantly improved GAD specific activity (from 10.4 U/mg to 80.0 U/mg), which also presented perfect adaptability for other disulfide-bond-containing proteins, for instance, UDP-glucosyltransferase from Arabidopsis thaliana. Taken together, our work demonstrated that the activity of GAD in B. licheniformis was regulated by the disulfide bonds formation status and provided a promising platform for the expression of disulfide-bond-containing proteins.

Laser microporation facilitates topical drug delivery: a comprehensive review about preclinical development and clinical application.

INTRODUCTION: Topical drug delivery is highly attractive and yet faces tissue barrier challenges. Different physical and chemical methods have been explored to facilitate topical drug delivery. AREAS COVERED: Ablative fractional laser (AFL) has been widely explored by the scientific community and dermatologists to facilitate topical drug delivery since its advent less than two decades ago. This review introduces the major efforts in exploration of AFL to facilitate transdermal, transungual, and transocular drug delivery in preclinical and clinical settings. EXPERT OPINION: Most of the preclinical and clinical studies find AFL to be safe and highly effective to facilitate topical drug delivery with little restriction on physicochemical properties of drugs. Clinical studies support AFL to enhance drug efficacy, shorten treatment time, reduce pain, improve cosmetic outcomes, reduce systemic drug exposure, and improve safety. Considering most of the clinical trials so far involved a small sample size and were in early phase, future trials will benefit from enrolling a large group of patients for thorough evaluation of the safety and efficacy of AFL-assisted topical drug delivery. The manufacturing of small and less costly AFL devices will also facilitate the translation of AFL-assisted topical drug delivery.

Effective adjuvantation of nanograms of influenza vaccine and induction of cross-protective immunity by physical radiofrequency adjuvant.

Novel adjuvants are highly demanded to aid in development of improved or new vaccines against existing or emerging infectious diseases. Considering commonly used Alum and MF59 adjuvants induce tissue stress and release of endogenous danger signals to mediate their adjuvant effects, physical modalities may be used to induce tissue stress and endogenous danger signal release to enhance vaccine-induced immune responses. Furthermore, physical adjuvants are less likely to induce significant systemic adverse reactions due to their localized effects. Recently we found non-invasive radiofrequency (RF) pretreatment of the skin could significantly enhance intradermal vaccine-induced immune responses in murine models that included pandemic influenza vaccine, pre-pandemic vaccine, and influenza internal antigen vaccine. It remained to be explored whether the physical RF adjuvant (RFA) could be used to boost seasonal influenza vaccination, spare vaccine doses, and induce cross-protective immunity. This study found the physical RFA could significantly enhance seasonal influenza vaccine-induced immune responses against each viral strain and robustly enhance low-dose (nanograms) H3N2 vaccine-induced immune responses and protection in murine models. RFA also induced cross-protective immunity against heterologous and heterosubtypic influenza viruses. Further studies found heat shock protein 70 (inducible endogenous danger signal) and myeloid differentiation primary response 88 adaptor played a crucial role in dose-sparing effects of RFA. These data strongly support further development of the physical RFA to boost influenza vaccination.

Developments on the Smart Hydrogel-Based Drug Delivery System for Oral Tumor Therapy.

At present, an oral tumor is usually treated by surgery combined with preoperative or postoperative radiotherapies and chemotherapies. However, traditional chemotherapies frequently result in substantial toxic side effects, including bone marrow suppression, malfunction of the liver and kidneys, and neurotoxicity. As a new local drug delivery system, the smart drug delivery system based on hydrogel can control drug release in time and space, and effectively alleviate or avoid these problems. Environmentally responsive hydrogels for smart drug delivery could be triggered by temperature, photoelectricity, enzyme, and pH. An overview of the most recent research on smart hydrogels and their controlled-release drug delivery systems for the treatment of oral cancer is given in this review. It is anticipated that the local drug release method and environment-responsive benefits of smart hydrogels will offer a novel technique for the low-toxicity and highly effective treatment of oral malignancy.