A Mendelian randomization study between chronic periodontitis and non-alcoholic fatty liver disease.

BACKGROUND AND OBJECTIVE: Observational studies have suggested a potential association between non-alcoholic fatty liver disease (NAFLD) and chronic periodontitis (CP). However, these studies are prone to confounding factors. The aim of this study was to assess the causal relationship between NAFLD and CP using a two-sample bidirectional Mendelian randomization (MR) analysis method. METHODS: Datasets of CP and NAFLD were retrieved from the European database, and instrumental variables (IVs) related to exposure were selected for the MR analysis. Sensitivity tests, including heterogeneity and horizontal pleiotropy tests, were conducted to ensure the consistency of the selected IVs, following which the analysis results were visualized. RESULTS: Genetic variants associated with CP and NAFLD were identified as IVs, and the MR assessment was performed using the summary data (CP: 3046 cases and 195 395 controls; NAFLD: 894 cases and 217 898 controls). CP increased the risk of NAFLD (inverse variance weighted [IVW], b = 0.132 > 0, p = .006 < .05), whereas the reverse was not observed (IVW, b = -0.024 < 0, p = .081 > .05). The sensitivity analysis indicated no heterogeneity or horizontal pleiotropy. CONCLUSION: The MR analysis suggested that CP could increase the risk of NAFLD among European populations.

Natural killer group 2D receptor and its ligands in cancer immune escape.

The immune system plays important roles in tumor development. According to the immune-editing theory, immune escape is the key to tumor survival, and exploring the mechanisms of tumor immune escape can provide a new basis for the treatment of tumors. In this review, we describe the mechanisms of natural killer group 2D (NKG2D) receptor and NKG2D ligand (NKG2DL) in tumor immune responses.Natural killer (NK) cells are important cytotoxic cells in the immune system, and the activated NKG2D receptor on the NK cell surface can bind to NKG2DL expressed in tumor cells, enabling NK cells to activate and kill tumor cells. However, tumors can escape the immune clearance mediated by NKG2D receptor/NKG2DL through various mechanisms. The expression of NKG2D receptor on NK cells can be regulated by cells, molecules, and hypoxia in the tumor microenvironment. Tumor cells regulate the expression of NKG2DL at the level of transcription, translation, and post-translation and thereby escape recognition by NK cells. In particular, viruses and hormones have special mechanisms to affect the expression of NKG2D receptor and NKG2DL. Therefore, NKG2D\NKG2DL may have applications as targets for more effective antitumor therapy.

Adaptive digital fringe projection technique for high dynamic range three-dimensional shape measurement.

It is a challenge for any optical method to measure objects with a large range of reflectivity variation across the surface. Image saturation results in incorrect intensities in captured fringe pattern images, leading to phase and measurement errors. This paper presents a new adaptive digital fringe projection technique which avoids image saturation and has a high signal to noise ratio (SNR) in the three-dimensional (3-D) shape measurement of objects that has a large range of reflectivity variation across the surface. Compared to previous high dynamic range 3-D scan methods using many exposures and fringe pattern projections, which consumes a lot of time, the proposed technique uses only two preliminary steps of fringe pattern projection and image capture to generate the adapted fringe patterns, by adaptively adjusting the pixel-wise intensity of the projected fringe patterns based on the saturated pixels in the captured images of the surface being measured. For the bright regions due to high surface reflectivity and high illumination by the ambient light and surfaces interreflections, the projected intensity is reduced just to be low enough to avoid image saturation. Simultaneously, the maximum intensity of 255 is used for those dark regions with low surface reflectivity to maintain high SNR. Our experiments demonstrate that the proposed technique can achieve higher 3-D measurement accuracy across a surface with a large range of reflectivity variation.

Targeting gut and intratumoral microbiota: a novel strategy to improve therapy resistance in cancer with a focus on urologic tumors.

INTRODUCTION: Growing attention has been drawn to urologic tumors due to their rising incidence and suboptimal clinical treatment outcomes. Cancer therapy resistance poses a significant challenge in clinical oncology, limiting the efficacy of conventional treatments and contributing to disease progression. Recent research has unveiled a complex interplay between the host microbiota and cancer cells, highlighting the role of the microbiota in modulating therapeutic responses. AREAS COVERED: We used the PubMed and Web of Science search engines to identify key publications in the fields of tumor progression and urologic tumor treatment, specifically focusing on the role of the microbiota. In this review, we summarize the current literature on how microbiota influence the tumor microenvironment and anti-tumor immunity, as well as their impact on treatments for urinary system malignancies, highlighting promising future applications. EXPERT OPINION: We explore how the composition and function of the gut microbiota influence the tumor microenvironment and immune response, ultimately impacting treatment outcomes. Additionally, we discuss emerging strategies targeting the microbiota to enhance therapeutic efficacy and overcome resistance. The application of antibiotics, fecal microbiota transplantation, and oncolytic bacteria has improved tumor treatment outcomes, which provides a novel insight into developing therapeutic strategies for urologic cancer.

A glycosylation risk score comprehensively assists the treatment of bladder neoplasm in the real-world cohort, including the tumor microenvironment, molecular and clinical prognosis.

Background: Bladder cancer is a common urological cancer associated high significant morbidity and mortality rates. Immunotherapy has emerged as a promising treatment option, although response rates vary among patients. Glycosylation has been implicated in tumorigenesis and immune regulation. However, our current comprehensive understanding of the role of glycosylation in bladder cancer and its clinical implications is limited. Methods: We constructed a training cohort based on the downloaded TCGA-BLCA dataset, while additional datasets (Xiangya cohort, GSE32894, GSE48075, GSE31684, GSE69795 and E-MTAB-1803) from Xiangya hospital, GEO and ArrayExpress database were obtained and used as validation cohorts. To identify glycosylation-related genes associated with prognosis, univariate Cox regression and LASSO regression were performed. A Cox proportional hazards regression model was then constructed to develop a risk score model. The performance of the risk score was assessed in the training cohort using Kaplan-Meier survival curves and ROC curves, and further validated in multiple validation cohorts. Results: We classified patients in the training cohort into two groups based on glycosylation-related gene expression patterns: Cluster 1 and Cluster 2. Prognostic analysis revealed that Cluster 2 had poorer survival outcomes. Cluster 2 also showed higher levels of immune cell presence in the tumor microenvironment and increased activation in key steps of the cancer immune response cycle. We developed an independent prognostic risk score (p < 0.001) and used it to construct an accurate prognostic prediction nomogram. The high glycosylation risk score group exhibited higher tumor immune cell infiltration, enrichment scores in immune therapy-related pathways, and a tendency towards a basal subtype. Conversely, the low-risk score group had minimal immune cell infiltration and tended to have a luminal subtype. These findings were consistent in our real-world Xiangya cohort. Conclusion: This multi-omics glycosylation score based on these genes reliably confirmed the heterogeneity of bladder cancer tumors, predicted the efficacy of immunotherapy and molecular subtypes, optimizing individual treatment decisions.

Molecular vasculogenic mimicry-Related signatures predict clinical outcomes and therapeutic responses in bladder cancer: Results from real-world cohorts.

Bladder cancer (BLCA) is a heterogeneous disease, and there are many classical molecular subtypes that reflect tumor immune microenvironment (TME) heterogeneity but their clinical utility is limited and correct individual treatment and prognosis cannot be predicted based on them. To find reliable and effective biomarkers and tools for predicting patients' clinical responses to several therapies, we developed a new systemic indicator of molecular vasculogenic mimicry (VM)-related genes mediated by molecular subtypes based on the Xiangya cohort and additional external BLCA cohorts using a random forest algorithm. A correlation was then done between the VM_Score and classical molecular subtypes, clinical outcomes, immunophenotypes, and treatment options for BLCA. With the VM_Score, it is possible to predict classical molecular subtypes, immunophenotypes, prognosis, and therapeutic potential of BLCA with high accuracy. The VM_Scores of high levels indicate a more anticancer immune response but a worse prognosis due to a more basal and inflammatory phenotype. The VM_Score was also found associated with low sensitivity to antiangiogenic and targeted therapies targeting the FGFR3, ß-catenin, and PPAR-γ pathways but with high sensitivity to cancer immunotherapy, neoadjuvant chemotherapy, and radiotherapy. A number of aspects of BLCA biology were reflected in the VM_Score, providing new insights into precision medicine. Additionally, the VM_Score may be used as an indicator of pan-cancer immunotherapy response and prognosis.

Renal pedicle lymphatic ligation for non-parasitic chyluria via retroperitoneal laparoscopic surgery: a single-center 12-year experience.

Background: Chyluria is a rare disease in which chylous is excreted in the urine. Currently, management of chyluria includes conservative treatments and surgical measures. This study aimed to report our experience in treating non-parasitic chyluria with retroperitoneal laparoscopic ligation of the renal lymphatic vessels. Methods: Data from 52 patients who underwent retroperitoneoscopic ligation of the renal lymphatic vessels for non-parasitic chyluria between December 2009 and May 2022 were reviewed. After general anesthesia, the patients were passively placed in the healthy lateral decubitus position and underwent three-port retroperitoneal laparoscopy. Detailed medical data, including demographic characteristics, intraoperative outcomes, postoperative data, and complications, were reviewed. Results: Fifty-two patients received surgery treatment at our institution. The mean disease course was 89.3 months. The mean age was 58.8 years, with females accounting for 57.7% (30/52); the majority of patients (33/52) had the laterality of chyluria on the left and 9 (17.3%) had a history of previous thoracic or abdominal surgery. Compared with the urine and blood data before the operation and on the first day after the operation, urinary protein, urinary tract infection, urinary red blood cells, hemoglobin, albumin, and serum total protein significantly improved 3 months after the operation. However, there were no significant differences in blood creatinine and blood urea nitrogen levels among the three groups. The mean surgery time was about 110.0 minutes, and the estimated total blood loss was 81.2 mL. The postoperative drainage volume was 229.9 mL. The average time to start a liquid diet and to be out of bed were 1.5 and 1.9 days, respectively. Transient postoperative gross hematuria occurred in eight patients, and complications occurred in five patients after surgery. The mean length of hospitalization was 6.6 days. The follow-up duration ranged from 3 to 152 months, and except for three patients who did not respond to treatment, the remaining patients had no recurrence and did not require reoperation. Conclusions: Our long-term follow-up results showed that renal pedicle lymphatic ligation via retroperitoneal laparoscopic surgery is an effective, safe, and reliable surgical option for patients with non-parasitic chyluria.

Perfect match: mTOR inhibitors and tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is an autosomal dominant syndrome that presents with diverse and complex clinical features and involves multiple human systems. TSC-related neurological abnormalities and organ dysfunction greatly affect the quality of life and can even result in death in patients with TSC. It is widely accepted that most TSC-related clinical manifestations are associated with hyperactivation of the mammalian target of rapamycin (mTOR) pathway caused by loss­of­function mutations in TSC1 or TSC2. Remarkable progress in basic and translational research has led to encouraging clinical advances. Although mTOR inhibitors (rapamycin/everolimus) demonstrate great potential in TSC management, two major concerns hamper their generalized application. One is the frequent manifestation of adverse events, such as stomatitis, infections, and menstrual disorders; and the other is the poor response in certain patients. Thus, indicators are required to effectively predict the efficacy of mTOR inhibitors. Herein, we have summarized the current utilization of mTOR inhibitors in the treatment of TSC and focused on their efficacy and safety, in an attempt to provide a reference to guide the treatment of TSC.

One-Step Ultraviolet Laser-Induced Fluorine-Doped Graphene Achieving Superhydrophobic Properties and Its Application in Deicing.

Joule heaters based on flexible thin films have attracted a significant amount of attention in both academia and the industry. However, it has been highly challenging to fabricate such heaters. In this study, a one-step laser induction method was proposed to prepare fluorine-doped laser-induced graphene (F-LIG) with stable and superhydrophobic properties by confining a 355 nm ultraviolet laser at the interface between the fluorinated ethylene propylene (FEP) film and polyimide (PI) film. The superhydrophobic properties of the F-LIG composite films could be attributed to the doping of fluorine elements and the laser-processed microstructures, which could be tuned by laser processing parameters. Based on the processed F-LIG films, Joule deicing heaters were developed and their deicing efficiencies are 7 times higher than that of the undoped LIG-based deicing heater. The method will provide new means and ideas to develop LIG-based flexible devices.

Robust pyroptosis risk score guides the treatment options and predicts the prognosis of bladder carcinoma.

Background: Bladder carcinoma (BLCA) is a heterogeneous disease that makes it difficult to achieve proper individual treatment and predict prognosis. This study aimed to develop a risk score from a new perspective of pyroptosis and guide accurate treatment and prognosis prediction for BLCA. Methods: The TCGA-BLCA cohort data were downloaded from The Cancer Genome Atlas database. Two external validation cohorts were collected from the Gene Expression Omnibus. Another independent validation cohort (the Xiangya cohort) was recruited from our hospital. The least absolute shrinkage and selector operation (LASSO) algorithm and Cox regression models were used to establish the pyroptosis risk score. Thereafter, we correlated the pyroptosis risk score with prognosis, tumor microenvironment (TME) immune hallmarks, and multiple treatments, including anticancer immunotherapy, chemotherapy, radiotherapy, and targeted therapy. Results: The pyroptosis risk score was an independent prognostic predictor of BLCA. We found that the activities of multiple steps of the anticancer immune response cycle, such as the release of cancer cell antigens, CD8 T cell recruitment, and NK cell recruitment, were significantly higher in the high-risk score group than in the low-risk score group. In addition, the infiltration levels of the corresponding tumor-infiltrating immune cells (TIICs), such as CD8 T cells and NK cells, were positively correlated with the pyroptosis risk score. Thus, BLCA with a high-risk score may be associated with inflamed phenotypes. Simultaneously, the expression of multiple immune checkpoints (such as PD-L1, CTLA-4, and PD-1) and enrichment scores of gene signatures positively correlated with immunotherapy response were positively correlated with the pyroptosis risk score. Therefore, patients with a high pyroptosis risk score may be more sensitive to immunotherapy. In addition, patients with high pyroptosis risk scores may be more sensitive to chemotherapeutic drugs, such as cisplatin, docetaxel, and paclitaxel. In addition, the pyroptosis risk score accurately predicted the molecular subtypes of BLCA, which were cross-validated in several independent systems. Conclusions: This study developed and validated a robust pyroptosis risk score that can predict the clinical outcomes and TME immune phenotypes of BLCA. In summary, the pyroptosis risk score helps drive precision therapy in patients with BLCA.

Gut Microbiota and Tumor Immune Escape: A New Perspective for Improving Tumor Immunotherapy.

The gut microbiota is a large symbiotic community of anaerobic and facultative aerobic bacteria inhabiting the human intestinal tract, and its activities significantly affect human health. Increasing evidence has suggested that the gut microbiome plays an important role in tumor-related immune regulation. In the tumor microenvironment (TME), the gut microbiome and its metabolites affect the differentiation and function of immune cells regulating the immune evasion of tumors. The gut microbiome can indirectly influence individual responses to various classical tumor immunotherapies, including immune checkpoint inhibitor therapy and adoptive immunotherapy. Microbial regulation through antibiotics, prebiotics, and fecal microbiota transplantation (FMT) optimize the composition of the gut microbiome, improving the efficacy of immunotherapy and bringing a new perspective and hope for tumor treatment.

Interfacial Laser-Induced Graphene Enabling High-Performance Liquid-Solid Triboelectric Nanogenerator.

Laser-induced graphene (LIG) has emerged as a promising and versatile method for high-throughput graphene patterning; however, its full potential in creating complex structures and devices for practical applications is yet to be explored. In this study, an in-situ growing LIG process that enables to pattern superhydrophobic fluorine-doped graphene on fluorinated ethylene propylene (FEP)-coated polyimide (PI) is demonstrated. This method leverages on distinct spectral responses of FEP and PI during laser excitation to generate the environment preferentially for LIG formation, eliminating the need for multistep processes and specific atmospheres. The structured and water-repellant structures rendered by the spectral-tuned interfacial LIG process are suitable as the electrode for the construction of a flexible droplet-based electricity generator (DEG), which exhibits high power conversion efficiency, generating a peak power density of 47.5 W m-2 from the impact of a water droplet 105 µL from a height of 25 cm. Importantly, the device exhibits superior cyclability and operational stability under high humidity and various pH conditions. The facile process developed can be extended to realize various functional devices.

Ladderlike Conical Micropillars Facilitating Underwater Gas-Bubble Manipulation in an Aqueous Environment.

Underwater gas-bubble manipulation in aqueous environments is of great importance in industry and academia. Although the underwater gas bubble has been proved to be directionally transportable by various structures, transporting gas bubbles in 3D space remains a challenge. In this research, two kinds of tapered pillars, that is, ladderlike and helical ladderlike, were proposed for manipulating gas bubbles. To fabricate such unique structures, an improved alternative coating and etching method was developed. To meet the requirements of underwater gas-bubble transport, a modified gas-bubble slippery technology was also developed to enhance the aerophilic ability. The dynamics of the gas bubble was analyzed using a high-speed camera. The Laplace force that resulted from the geometry gradient was found to play a significant role in tuning the gas-bubble velocity. Through adjustments on the wettability, tilt angle, and geometry of each section of the tapered pillar, tuning the transport velocity from 113.9 ± 10.3 to 309.1 ± 5.8 mm/s becomes possible. On the basis of these findings, the helical ladderlike tapered pillar was fabricated and demonstrated to be able to transport gas bubbles in 3D space. These results may provide a new and systematic way to design and fabricate materials and structures for directional gas-bubble transport in 3D space.

Evaluation Algorithm of Root Canal Shape Based on Steklov Spectrum Analysis.

In recent years, we have seen more and more interest in the field of medical images and shape comparison motivated by the latest advances in microcomputed tomography (µCT) acquisition, modelling, and visualization technologies. Usually, biologists need to evaluate the effect of different root canal preparation systems. Current root canal preparation evaluation methods are based on the volume difference, area difference, and transportation of two root canals before and after treatment. The purpose of root canal preparation is to minimize the volume difference and ensure the complete removal of the smear layer. Previous methods can reflect some general geometric differences, but they are not enough to evaluate the quality of root canal shape. To solve this problem, we proposed a novel root canal evaluation method based on spectrum and eigenfunctions of Steklov operators, which can be served as a better alternative to current methods in root canal preparation evaluation. Firstly, the ideal root canal model was simulated according to the root canal model before and after preparation. Secondly, the Steklov spectrum of the two models was calculated. Thirdly, based on the spectrum and the histogram of the Gaussian curvature on the surface, the weight of each eigenvalue was computed. Therefore, the Steklov spectrum distance (SSD), which measures shape difference between the root canals, was defined. Finally, the calculation method that quantifies the root canal preparation effect of root canals was obtained. Through experiments, our method manifested high robustness and accuracy compared with existing state-of-the-art approaches. It also demonstrates the significance of our algorithm's advantages on a variety of challenging root canals through result comparison with counterpart methods.

Ladderlike Tapered Pillars Enabling Spontaneous and Consecutive Liquid Transport.

Directional liquid transport has significant domestic and industrial applications. Tapered objects have theoretically and experimentally been demonstrated to have the ability to spontaneously transport liquids. However, the transporting distance is limited, and consecutively and spontaneously transporting liquids has always been a challenge. In this work we proposed to exploit ladderlike tapered pillars, which are inspired by relay races, to increase the transport distance. These pillars were designed using a developed numerical model and fabricated by a novel alternating etching and coating method followed by wettability enhancement. We demonstrated through experiments that the resulting pillars could consecutively and spontaneously transport a liquid droplet at an average velocity of 0.139 m/s with a maximum acceleration of 5 g. The optimum window of the tilt angle range (0°-25°), contact angle (50°), and the chemical modification time (5 min) were obtained. Such ladderlike tapered pillars are able to improve the water-collection efficiency. These results may provide a new and systematic way to design and fabricate materials and structures for directional liquid transport.

Effects of Defects on the Mechanical Properties of Kinked Silicon Nanowires.

Kinked silicon nanowires (KSiNWs) have many special properties that make them attractive for a number of applications. The mechanical properties of KSiNWs play important roles in the performance of sensors. In this work, the effects of defects on the mechanical properties of KSiNWs are studied using molecular dynamics simulations and indirectly validated by experiments. It is found that kinks are weak points in the nanowire (NW) because of inharmonious deformation, resulting in a smaller elastic modulus than that of straight NWs. In addition, surface defects have more significant effects on the mechanical properties of KSiNWs than internal defects. The effects of the width or the diameter of the defects are larger than those of the length of the defects. Overall, the elastic modulus of KSiNWs is not sensitive to defects; therefore, KSiNWs have a great potential as strain or stress sensors in special applications.