Search

Abstract The purpose of this study was to investigate the causal association between unhealthy lifestyle style factors and the risk of colorectal cancer, with the aim of preventing the occurrence of colorectal cancer by modifying unhealthy lifestyles. A two-sample Mendelian randomization (MR) approach was employed in this study, utilizing the inverse-variance weighted method as the primary research method. This MR analysis analyzed data of 3022 colorectal cancer cases and 174,006 controls from the FinnGen database. Single nucleotide polymorphisms (SNPs) associated with unhealthy lifestyle factors were selected as instrumental variables (IVs), including two obesity-related indicators, BMI (body mass index) and WHR (waist-to-hip ratio). Four phenotypes of smoking (smoking initiation, ever smoked, smoking per day, smoking cessation) and one phenotype of alcohol consumption (drinks per week). Four phenotypes of physical activity (accelerometer-based physical activity, moderate-to-vigorous physical activity, vigorous physical activity, strenuous sports or other exercises). All SNPs were obtained from published genome-wide association studies. The study found that the obesity-related indicator, higher WHR (OR = 1.38, 95% CI 1.12–1.70; P = 0.002) were associated with an increased risk of colorectal cancer, and two smoking phenotypes, cigarettes per day(OR = 1.30, 95% CI 1.01–1.68; P = 0.042)and smoking initiation (OR = 3.48, 95% CI 1.15–10.55; P = 0.028), were potentially associated with an increased risk of colorectal cancer. However, there was no evidence to suggest that physical activities and alcohol consumption were associated with colorectal cancer (all p > 0.05). In addition, the study detected no pleiotropy (all p > 0.05). This MR analysis indicates a causal association between a higher waist-to-hip ratio and the risk of colorectal cancer and a suggestive association between smoking and the risk of colorectal cancer among Europeans. These findings contribute to the understanding of the etiology of colorectal cancer and have potential implications for its prevention.

Abstract Retinal ischemia‒reperfusion (I/R) injury can cause significant damage to human retinal neurons, greatly compromising their functions. Existing interventions have been proven to have little effect. Ferroptosis is a newly discovered type of programmed cell death that has been found to be involved in the process of ischemia‒reperfusion in multiple organs throughout the body. Studies have shown that it is also present in retinal ischemia‒reperfusion injury. A rat model of retinal ischemia‒reperfusion injury was constructed and treated with deferoxamine. In this study, we found the accumulation of Fe2+, reactive oxygen species (ROS), malondialdehyde (MDA), and the consumption of glutathione (GSH) via ELISA testing; increased expression of transferrin; and decreased expression of ferritin, SLC7A11, and GPX4 via Western blotting (WB) and real-time PCR testing. Structural signs of ferroptosis (mitochondrial shrinkage) were observed across multiple cell types, including retinal ganglion cells (RGCs), photoreceptor cells, and pigment epithelial cells. Changes in visual function were detected by F-VEP and ERG. The results showed that iron and oxidative stress were increased in the retinal ischemia‒reperfusion injury model, resulting in ferroptosis and tissue damage. Deferoxamine protects the structural and functional soundness of the retina by inhibiting ferroptosis through the simultaneous inhibition of hemochromatosis, the initiation of transferrin, and the degradation of ferritin and activating the antioxidant capacity of the System Xc-GSH-GPX4 pathway.

Abstract Urethral stricture refers to the narrowing of the urethral lumen. While previous studies have hinted at inflammation as the initial driver of this condition, the reasons and mechanisms behind its progression remain largely unknown. By Atomic force microscope (AFM), researchers measured the matrix stiffness of urethra to be 5.23 ± 0.37 kPa for normal tissue and 41.59 ± 2.48 kPa for stricture urethral scar. Similar results were observed in rat urethral stricture models, where the matrix stiffness of normal urethra was 4.29 ± 0.82 kPa, while 32.94 ± 7.12 kPa for urethral stricture scar. Notably, the matrix stiffness increased in rat models over time. To further investigate, polyacrylamide hydrogels were employed to mimic different levels of stiffness for normal and stricture condition. Interestingly, higher matrix stiffness led to an increased fibroblast-to-myofibroblast transition (FMT) in rat urethral fibroblasts, indicated by enhanced expression of α-SMA and Collagen I, as well as changing in the morphology of fibroblast. RNA-seq analysis suggested that Igfbp3/Smads might regulate the progressive FMT in urethral stricture. In the experiment where the expression of Igfbp3 was inhibited, increasing matrix stiffness lose the potential to stimulate FMT progression and the expression of p-Smad2/3 decreased. On the contrary, overexpression of Igfbp3 promoted the process of FMT in urethral fibroblasts. In conclusion, Igfbp3/Smad pathway appeared to be involved in the progression of urethral fibrosis. This finding suggested that Igfbp3/Smad might be an promising target for future research and treatment in this filed.

Abstract In this study, a series of true triaxial loading tests were carried out on coal-measure sandstone after high temperature treatment by using a self-developed true triaxial test system combined with acoustic emission (AE) monitoring, and the mass loss, deformation characteristics and loss failure mode of sandstone before and after heat treatment were systematically studied. It is found that the true triaxial mechanical properties of sandstone after high temperature treatment are closely related to temperature, and the peak strength, maximum principal strain, volume strain, minimum fracture angle and elastic modulus, which all showed bimodal changes, and 800 °C is the threshold temperature of the first four parameters. The transition temperature of the elastic modulus is 400 °C. It is found that the test results of true triaxial high temperature sandstone are in good agreement with the existing true triaxial theory and test results. The failure forms of the samples at different temperatures show inverted “Y” or inverted “N” shapes. Shear failure occurs when the temperature is below 400 °C, and shear-tension failure occurs when the temperature is above 600 °C. At the same time, it is found that the AE signal has four periods, namely the quiet period, growth period, explosion period and decline period. The number of AE events corresponds to the deviatoric stress interval well. Experimental study of the mechanical properties of sandstone under the coupling effect of high temperature and true triaxial stress has guiding significance for the parameter selection and safety evaluation of roof sandstone in underground coal gasification.

Abstract The occlusion of dentinal tubules has become a rapid and effective method for treating dentin hypersensitivity. Accurate evaluation of dentin occlusion is critical to illustrate the efficacy of oral care products and to optimize dental therapy in the clinics, which is limited by the conventional two-dimensional (2-D) characterization methods. Here, we demonstrate the visualization of the dentin occlusion via three-dimensional (3-D) characterization using a focused ion beam-scanning electron microscopy (FIB-SEM) tomography. Using the “Slice and View” approach, the material used for occluding dentin tubules is imaged with a very high-resolution voxel (10 nm × 10 nm × 20 nm) from 2-D SEM images and then reconstructed into a 3-D volume, which presents the mode of action of toothpaste for treating dentin hypersensitivity. Meanwhile, quantitative analysis of the depth of occlusion is successfully obtained. This work validates the feasibility of FIB-SEM tomography in the analysis of dentin occlusion within the complicated networks of dentine tubules at the nanoscale, and provides a novel approach to facilitate the research and development of oral care products.

Abstract A deformable microfluidic system and a fluidic dynamic model have been successfully coupled to understand the dynamic fluid–structure interaction in transient flow, designed to understand the dentine hypersensitivity caused by hydrodynamic theory. The Polydimethylsiloxane thin sidewalls of the microfluidic chip are deformed with air pressure ranging from 50 to 500 mbar to move the liquid meniscus in the central liquid channel. The experiments show that the meniscus sharply increased in the first 10th of second and the increase is nonlinearly proportional to the applied pressure. A theoretical model is developed based on the unsteady Bernoulli equation and can well predict the ending point of the liquid displacement as well as the dynamics process, regardless of the wall thickness. Moreover, an overshooting and oscillation phenomenon is observed by reducing the head loss coefficient by a few orders which could be the key to explain the dentine hypersensitivity caused by the liquid movement in the dentine tubules.

Abstract Prostate cancer (PCa) is a common malignant disease among men and biochemical recurrence (BCR) is considered to be a decisive risk factor for clinical recurrence and PCa metastasis. Clarifying the genes related to BCR and its possible pathways is vital for providing diagnosis and treatment methods to delay the progress of BCR. An analysis of data concerning PCa from previous datasets of The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) was performed. Immunohistochemical (IHC) staining were used to evaluate the expression of SLC14A1 in prostate tissues. Kaplan–Meier analysis, Pearson correlation, and single sample Gene Set Enrichment Analysis (ssGSEA) were used to identify the potential pathway and molecular mechanism of the function of SLC14A1 in BCR of PCa. The expression of SLC14A1 is significantly reduced in prostate cancer cells and tissue comparing to normal prostate epithelial cell and para-cancerous tissue. As indicated by Kaplan–Meier analysis, High expression of SLC14A1 could increase the BCR-free survival time of PCa patients. This effect might be related to the interaction with miRNAs (has-miR-508, has-mir-514a2, and has-mir-449a) and the infiltration of B cells. SLC14A1 is a novel important gene associated with BCR of PCa, and further studies of its molecular mechanism may delay the progress of BCR.

Abstract Secondary epidermoid cyst of the penis is a very rare epidermoid cyst that occurs in the penis. The purpose of this study was to investigate the relationship between the occurrence of secondary epidermoid cyst of penis and circumcision-related factors, and to provide possible reasonable and effective suggestions for circumcision. The data of all patients who visited the clinic for epidermoid cysts of the penis from September 2000 to September 2021 in Xiangya Hospital were collected. A retrospective study was carried out on whether the patients had been circumcised and the surgical method, anesthesia method, cyst location, surgical age, postoperative wound infection, whether they were phimosis patients, and the level of the surgeon. Among the 24 patients followed up, 95.8% had a history of circumcision, and only 4.2% had no history of circumcision, and the more traumatic surgical methods developed secondary epidermoid cyst of the penis after surgery the higher the probability. Injecting anesthesia at the base of the penis increases the chances of developing a secondary epidermoid cyst of the penis. Postoperative secondary epidermoid cyst of the penis were mainly located in the anterior segment and posterior segment, and the anterior segment had a higher proportion, followed by the posterior segment. Secondary epidermoid cyst of the penis occur mainly in adults. Postoperative wound infection accelerates the appearance of secondary epidermoid cyst of the penis. Patients with phimosis have an increased probability of developing secondary epidermoid cysts of the penis after surgery. The incidence of secondary epidermoid cysts and postoperative infection after manual circumcision by the attending physician was higher than that of the chief physician. Circumcision, injection of anesthesia at the base of the penis, ligation of the penis, and postoperative wound infection may be the etiologies and triggers of secondary epidermoid cysts of the penis. Adults and phimosis patients may be high-risk groups. Lower-level surgeons may increase the odds of postoperative secondary epidermoid cysts of the penis, and it is recommended that surgery be performed by a clinically-experienced, higher-level surgeon. The indications for circumcision should be strictly evaluated and the operation should be performed as soon as possible, and the less invasive surgical method and anesthesia method should be selected. Reduce irrelevant operations during surgery and avoid wound infection after surgery.

Abstract Urethral stricture is related to scar tissue fibrosis, but its pathogenesis is still unclear. This study aims to explore the regulatory mechanism of circular RNA (circRNA) in the occurrence and development of urethral stricture. CircRNA microarray was employed to analyze circRNA expression profiles between human urethral scar tissue and normal urethral tissue. The results of circRNA microarray showed that there were 296 differentially expressed genes between urethral scar tissue and normal urethral tissue. The enrichment analysis of Kyoto encyclopedia of genes and genomes showed that these circRNAs were significantly correlated with ECM–receptor interaction. The first nine differentially expressed circRNA were selected to predict the circRNA–miRNA network. RT-qPCR results showed that circ_0047339 was upregulated considerably in urethral scar tissue. Urethral scar fibroblasts were isolated from human urethral scar tissue and cultured in vitro. After silencing circ_0047339, the proliferation of urethral scar cells decreased significantly, and the expressions of Collagen I (COL-1) and α-smooth muscle actin (α-SMA) also reduced. As a competing endogenous RNA, circ_0047339 could increase the expression of TSP-1 by competitively binding miR-4691-5p. In addition, miR-4691-5p mimic transfection could inhibit the proliferation of urethral scar fibroblasts and the presentation of thrombospondin-1 (TSP-1), α-SMA and COL-1, while circ_0047339 overexpression eliminated this inhibition. Our results showed that circ_0047339 might promote the growth and fibrosis of urethral scar fibroblasts through miR-4691-5p/TSP-1 axis, thus promoting the development of urethral stricture.

Abstract Scanning Electron Microscope/Focused Ion Beam (SEM/FIB) system has become valuable and popular tool for the analysis of biological materials such as dentine structures. According to physiological and anatomical studies, dentine structures are a complicated system containing collagen fibers, nanocrystalline hydroxyapatite, and numerous networks of tubular pores. During a routine FIB milling process, collagen fibers and other organic structures are vaporized, which increases the number of pores on the milled surface of the dentine. This causes the final cross-section to be more porous than the pristine sample. Unfortunately, little attention has been paid to the collagen fiber loss and how to preserve them during a FIB milling process. In this work, we present a novel and simple approach to preserve the organic portions of the dentine structure through metal staining. By using this method, the porosity of the dentine structure after the FIB milling process is significantly reduced similar to the pristine sample. This indicates that the organic portion of the dentine structure is well protected by the metal staining. This approach enables the SEM/FIB system to generate super-high quality SEM images with less ion beam damage; and the SEM images can better reflect the original condition of the dentine structure. Further, serial energy-dispersive X-ray spectroscopy (EDS) mapping of the stained dentine structure is achieved without an additional metal coating; and three-dimensional (3-D) elemental mapping of an occluded dentine is achieved with a significantly reduced data acquisition time.

Abstract Polymer coatings are commonly used to protect carbon steels from corrosion but they are susceptible to weathering and many of them have environmental concerns. Therefore, we studied the possibility of an environmentally favorable inorganic magnesium phosphate cement (MPC) coating for protecting mild steel. A formulation suitable for coating steel was developed by compositional modification [i.e., incremental replacement of dead-burned magnesia (MgO) with magnesium hydroxide (Mg(OH)2)] to a road-repair MPC. This modification yielded an acceptable working time and prevented pore formation at the coating-steel interface. Corrosion monitoring by linear polarization and electrochemical impedance spectroscopy for 14 days found that, the MPC coating substantially increased the linear polarization resistance (Rp) [e.g., day 1: (8.2 ± 1.7) × 103 (nadir value) vs. 495 ± 55 Ω cm−2] and charge transfer resistance (Rct) (e.g., day 1: 9.3 × 103 vs. 3.8 × 102 Ω cm−2). The coated steel underwent neutral sodium chloride (NaCl) salt spray for 2400 h without visible rusting. Immersion for 24 h in liquids simulating the pore fluid indicated that, passivation by the excess MgO in the coating was a major contributor to its anti-corrosive property. Tafel polarization in the liquids found that, corrosion current density (Icorr) followed the rank: 3.5% NaCl solution (6.0 µA cm−2) > 3.5% NaCl solution containing MgO (3.6 µA cm−2) > 3.5% NaCl solution containing fragmented MPC (1.7 µA cm−2), suggesting that a physical barrier effect and dissolved phosphate ions improved its protection. This study shows that, MPC coating is a promising durable and environmentally favorable anti-corrosive material for protecting steel structures in some applications.

Abstract Previous trial evidence suggested potential risk of serious urinary tract infections (UTIs) and genital infections in type 2 diabetes patients using sodium glucose co-transporter-2 inhibitors (SGLT2) inhibitors. We conducted a systematic review and meta-analysis to assess the effects of SGLT2 inhibitors on UTIs and genital infections in patients with type 2 diabetes. In total, 77 RCTs involving 50,820 participants were eligible. The meta-analyses of randomized controlled trials (RCTs) showed no significant difference in UTIs between SGLT2 inhibitors versus control (2,526/29,086 vs. 1,278/14,940; risk ratio (RR) 1.05, 95% confidence interval (CI) 0.98 to 1.12; moderate quality evidence), but suggested increased risk of genital infections with SGLT2 inhibitors (1,521/24,017 vs. 216/12,552; RR 3.30, 95% CI 2.74 to 3.99; moderate quality evidence). Subgroup analyses by length of follow up (interaction p = 0.005), type of control (interaction p = 0.04) and individual SGLT2 inhibitors (interaction p = 0.03) also showed statistically significant differences in genital infections. The upcoming major trials may provide important additional insights on UTIs, and more efforts are needed to address comparative effects of each individual SGLT2 inhibitors on the infections.

Abstract Little is known about how nematode ecology differs across elevational gradients. We investigated the soil nematode community along a ~2,200 m elevational range on Mt. Norikura, Japan, by sequencing the 18S rRNA gene. As with many other groups of organisms, nematode diversity showed a high correlation with elevation, and a maximum in mid-elevations. While elevation itself, in the context of the mid domain effect, could predict the observed unimodal pattern of soil nematode communities along the elevational gradient, mean annual temperature and soil total nitrogen concentration were the best predictors of diversity. We also found nematode community composition showed strong elevational zonation, indicating that a high degree of ecological specialization that may exist in nematodes in relation to elevation-related environmental gradients and certain nematode OTUs had ranges extending across all elevations, and these generalized OTUs made up a greater proportion of the community at high elevations – such that high elevation nematode OTUs had broader elevational ranges on average, providing an example consistent to Rapoport’s elevational hypothesis. This study reveals the potential for using sequencing methods to investigate elevational gradients of small soil organisms, providing a method for rapid investigation of patterns without specialized knowledge in taxonomic identification.

Abstract There is no consensus on the involvement of zinc (Zn) dysfunctions in Parkinson’s Disease (PD). We performed a meta-analysis to evaluate whether circulating Zn levels in the serum, plasma, and cerebrospinal fluid (CSF) are altered in PD. Twenty-three published studies were selected by searching the databases of PubMed and China National Knowledge Infrastructure (CNKI). A total of 803 PD patients and 796 controls, 342 PD patients and 392 controls, and 135 PD patients and 93 controls were included to study Zn levels in the serum, plasma, and CSF, respectively. Our meta-analysis showed that the serum Zn levels were significantly lower in PD patients compared with health controls (SMD = −0.59; 95% CI [−1.06, −0.12]; P = 0.014). A reduced Zn levels in PD patients were found when serum and plasma studies were analyzed together (SMD = −0.60, 95% CI [−0.98; −0.22]; p = 0.002). PD patients had a tendency toward reduced CSF Zn levels compared with health controls (SMD = −0.50; 95% CI [−1.76, 0.76]; P = 0.439), but no statistical significance was obtained and this data did not allow conclusions due to a small sample size of CSF studies. This study suggests that reduced Zn levels in the serum and plasma are associated with an increased risk for PD.

Physical activity and sleep are important factors of mental and physical health in children, with some reports indicating that their effects can persist into adulthood. However, there is limited research on the qualitative aspects of physical activity and sleep in preschool children, particularly in those aged < 3 years. Therefore, to elucidate the association between psychosocial health and physical activity/sleep in early childhood in terms of qualitative aspects, we conducted a retrospective cohort study in 2985 3-year-old children (37.2 ± 0.75 months) in Shanghai, China. An analysis using structural equation modeling indicated that current physical activity had a direct and moderate impact on current psychosocial health evaluated using the Strength and Difficulties Questionnaire. In particular, past physical activity had an indirect and mild effect on current psychosocial health via current physical activity in girls. However, regardless of sex, past sleep quality had slight impact on current psychosocial health, not only indirectly via current sleep quality, but also directly. These findings highlight the importance of considering the qualitative aspects of physical activity and sleep quality as significant factors influencing the current and future psychosocial health of children, even at a very early age (< 3 years)., (© 2023. Springer Nature Limited.)

The study aimed to assess whether aerobic exercise (AEx) training and a fibre-enriched diet can reduce hepatic fat content (HFC) and increase glycaemic control in pre-diabetic patients with non-alcoholic fatty liver disease (NAFLD). Six-hundred-and-three patients from seven clinics in Yangpu district, Shanghai, China were recruited. Of them 115 individuals aged 50-65-year fulfilled the inclusion criteria (NAFLD with impaired fasting glucose or impaired glucose tolerance) and were randomly assigned into exercise (AEx n = 29), diet (Diet n = 28), exercise plus diet (AED n = 29), or no-intervention (NI n = 29) groups. Progressive supervised AEx training (60-75% VO2max intensity) was given 2-3 times/week in 30-60 min/sessions, and the diet intervention was provided as lunch with 38% carbohydrate and diet fibre of 12 g/day for 8.6-month. HFC was assessed by 1 H MRS. We found that HFC was significantly reduced in the AEx (-24.4%), diet (-23.2%), and AED (-47.9%) groups by contrast to the 20.9% increase in the NI group (p = 0.001 for all) after intervention. However, only AED group significantly decreased HbA 1c (-4.4%, p = 0.01) compared with the NI group (-0.6%). Aerobic exercise training combined with fibre-enriched diet can reduce HFC more effectively than either exercise or increased fibre-intake alone in pre-diabetic patients with NAFLD.