Sucralose triggers insulin resistance leading to follicular dysplasia in mice.

Sucralose, the extensively utilized sweetener, might lead to metabolic disorders with prolonged consumption, but it remains uncertain if sucralose has any impact on female reproductive health. We incorporated sucralose into drinking water and observed food intake, body weight, estrous cycle, follicular development, serum hormones, and insulin sensitivity of mice. The mice did not experience any changes in their food intake or body weight after consuming sucralose. However, they displayed irregularities in the estrous cycle, marked by a reduced count of primordial, primary, and secondary follicles, coupled with a significant increase in the number of antral follicles. There was a decline in follicle-stimulating hormone (FSH), estradiol (E2), and progesterone (P4) levels, while testosterone (T) and luteinizing hormone (LH) levels surged, leading to a notable elevation in the LH / FSH ratio. Sucralose also induced insulin resistance, as evidenced by elevated insulin levels and impaired insulin tolerance, which responded to an increase in bacterial-derived serum endotoxin. By eliminating insulin resistance with rosiglitazone (RSG), eradicating intestinal flora-derived endotoxins with neomycin (NEO), or enhancing intestinal barrier function with indole-3-carbinol (I3C), the abnormalities in estrous cycle, disruptions in follicular development, hormonal imbalances and elevation in serum endotoxins induced by sucralose were successfully reversed. The present study indicates that sucralose-induced follicular dysplasia in mice is probably related to impaired intestinal permeability, infiltration of endotoxins, initiation of systemic inflammation, and insulin resistance.

Compressibility of lime-treated dredged slurry with high water content.

Lime is widely used for soft ground treatment, rendering the compressibility of lime-treated soil a crucial factor in deformation analysis in engineering applications. This study investigated the compressibility of three remoulded lime-treated slurries with high water content in Southeast China. Sixty groups of oedometer tests were conducted on lime-treated soils with an initial water content of 1 to 3 times the liquid limit and lime contents between 1 and 3%. The oedometer test results were discussed to examine the remoulded yield stress σ y ' of lime-treated slurry. Considering the relationships between σ y ' , the void ratio, lime content, and initial water content were preliminarily discussed and quantitatively established. Research on the normalised compression curve of lime-treated soil revealed that for soil samples containing a lime content of 0-%, the normalised compression curve at σ p ' > σ y ' can be represented by a unique line. Furthermore, the log(1 + e) - log σ v ' compression curve of lime-treated slurry at pre-yield state is analysed, and a prediction method for the modified compression index is proposed.

Unsupervised reconstruction with a registered time-unsheared image constraint for compressed ultrafast photography.

Compressed ultrafast photography (CUP) is a computational imaging technology capable of capturing transient scenes in picosecond scale with a sequence depth of hundreds of frames. Since the inverse problem of CUP is an ill-posed problem, it is challenging to further improve the reconstruction quality under the condition of high noise level and compression ratio. In addition, there are many articles adding an external charge-coupled device (CCD) camera to the CUP system to form the time-unsheared view because the added constraint can improve the reconstruction quality of images. However, since the images are collected by different cameras, slight affine transformation may have great impacts on the reconstruction quality. Here, we propose an algorithm that combines the time-unsheared image constraint CUP system with unsupervised neural networks. Image registration network is also introduced into the network framework to learn the affine transformation parameters of input images. The proposed algorithm effectively utilizes the implicit image prior in the neural network as well as the extra hardware prior information brought by the time-unsheared view. Combined with image registration network, this joint learning model enables our proposed algorithm to further improve the quality of reconstructed images without training datasets. The simulation and experiment results demonstrate the application prospect of our algorithm in ultrafast event capture.

Experimental Demonstration of a Tunable Energy-Selective Gamma-Ray Imaging System Based on Recoil Electrons.

The domain of gamma-ray imaging necessitates technological advancements to surmount the challenge of energy-selective imaging. Conventional systems are constrained in their dynamic focus on specific energy ranges, a capability imperative for differentiating gamma-ray emissions from diverse sources. This investigation introduces an innovative imaging system predicated on the detection of recoil electrons, addressing the demand for adjustable energy selectivity. Our methodology encompasses the design of a gamma-ray imaging system that leverages recoil electron detection to execute energy-selective imaging. The system's efficacy was investigated experimentally, with emphasis on the adaptability of the energy selection window. The experimental outcomes underscore the system's adeptness at modulating the energy selection window, adeptly discriminating gamma rays across a stipulated energy spectrum. The results corroborate the system's adaptability, with an adjustable energy resolution that coincides with theoretical projections and satisfies the established criteria. This study affirms the viability and merits of utilizing recoil electrons for tunable energy-selective gamma-ray imaging. The system's conceptualization and empirical validation represent a notable progress in gamma-ray imaging technology, with prospective applications extending from medical imaging to astrophysics. This research sets a solid foundation for subsequent inquiries and advancements in this domain.

Assessing mortality risk in Type 2 Diabetes patients with prolonged ASCVD risk factors: the inclusive Poh-Ai predictive scoring system with CAC Score integration.

PURPOSE: To enhance the predictive risk model for all-cause mortality in individuals with Type 2 Diabetes (T2DM) and prolonged Atherosclerotic Cardiovascular Disease (ASCVD) risk factors. Despite the utility of the Coronary Artery Calcium (CAC) score in assessing cardiovascular risk, its capacity to predict all-cause mortality remains limited. METHODS: A retrospective cohort study included 1929 asymptomatic T2DM patients with ASCVD risk factors, aged 40-80. Variables encompassed demographic attributes, clinical parameters, CAC scores, comorbidities, and medication usage. Factors predicting all-cause mortality were selected to create a predictive scoring system. By using stepwise selection in a multivariate Cox proportional hazards model, we divided the patients into three risk groups. RESULTS: In our analysis of all-cause mortality in T2DM patients with extended ASCVD risk factors over 5 years, we identified significant risk factors, their adjusted hazard ratios (aHR), and scores: e.g., CAC score > 1000 (aHR: 1.57, score: 2), CAC score 401-1000 (aHR: 2.05, score: 2), and more. These factors strongly predict all-cause mortality, with varying risk groups (e.g., very low-risk: 2.0%, very high-risk: 24.0%). Significant differences in 5-year overall survival rates were observed among these groups (log-rank test < 0.001). CONCLUSION: The Poh-Ai Predictive Scoring System excels in forecasting mortality and cardiovascular events in individuals with Type 2 Diabetes Mellitus and extended ASCVD risk factors.

Measurement of nanocomposite scintillators by terahertz time domain spectroscopy.

Nanocomposite scintillators are expected to combine the advantages of inorganic and plastic scintillators, such as high detection efficiency, high light yield, fast decay time, low cost, and ease of processing. They are currently the forefront and hot field of scintillator research. In this study, a non-destructive method was developed for measuring the content of inorganic components in nanocomposite scintillators by terahertz time-domain spectroscopy. The complex refractive index of B a F 2 nanocomposite scintillators with different mass contents was measured in the terahertz band. As the mass content of B a F 2 nanoparticles increases, the refractive index and extinction coefficient of B a F 2 nanocomposite scintillators also gradually increase in the terahertz band. By combining the effective medium theory, the expected mass content was obtained, proving the feasibility of this measuring method.

Snapshot compressive imaging at 855 million frames per second for aluminium planar wire array Z-pinch.

This paper present a novel, integrated compressed ultrafast photography system for comprehensive measurement of the aluminium planar wire array Z-Pinch evolution process. The system incorporates a large array streak camera and embedded encoding to improve the signal-to-noise ratio. Based on the "QiangGuang-I" pulsed power facility, we recorded the complete continuous 2D implosion process of planar wire array Z-Pinch for the first time. Our results contribute valuable understanding of imploding plasma instabilities and offer direction for the optimization of Z-Pinch facilities.

[Preparation and effectiveness evaluation of placebo of Jiawei Ermiao Granules].

This study explored the preparation process of the placebo of Jiawei Ermiao Granules and evaluated the placebo effect, aiming to provide qualified placebo samples for clinical trials of Jiawei Ermiao Granules and a reference for the preparation and quality evaluation of placebos of traditional Chinese medicine granules. On the basis of the comprehensive analysis results of Jiawei Ermiao Granules, the orthogonal experiment was conducted to optimize the flavoring agents and colorants. After manual evaluation, the placebo formula was determined as dextrin 10 g, Codonopsis Radix extract 5.0 g, bitter melon extract 1.6 g, Mume Fructus extract 0.3 g, stevioside 0.1 g, sucrose octaacetate 0.004 g, indigo 0.004 g, lemon yellow 0.003 1 g, sunset yellow 0.001 8 g, bitter tea powder 0.001 8 g, caramel 0.001 3 g. Pilot trials were conducted on the placebo formula. The simulation effect of placebo was evaluated independently and comparatively, and the objectively evaluated by electronic nose and electronic tongue. The results showed that the independent manual evaluation of the placebo formula had higher error rate, and the placebo and Jiawei Ermiao Granules showed the similarity of 99.61% in the comparative manual evaluation. The smell similarity between the placebo and Jiawei Ermiao Granules was 99.19%, and the electronic tongue test showed little difference in the taste. In conclusion, the placebo prepared in this study shows a high similarity to Jiawei Ermiao Granules, which is not easy to break the blindness when being applied to clinical trials. This study provides a reference for the preparation and quality evaluation and promotes the large-scale production of placebos of traditional Chinese medicine granules, playing a role in improving the persuasiveness and acceptance of the efficacy of traditional Chinese medicines.

Colchicine Alleviates Rosacea by Inhibiting Neutrophil Inflammation Activated by the TLR2 Pathway.

Rosacea is a chronic facial inflammatory skin disease that occurs with dysfunction of the immune system. Colchicine was reported to have anti-inflammatory properties. However, the impact of colchicine on rosacea remains unclear. In the present study, the phenotype of rosacea lesions was evaluated by the redness score, inflammatory biomarkers were analyzed by reverse transcription PCR (RT‒PCR), and the infiltration of inflammatory cells was assessed by IHC analysis and immunofluorescence in a rosacea-like mouse model. In vitro, RT‒PCR was used to identify the inflammatory factors that Toll-like receptor 2 (TLR2) agonist caused neutrophils to produce, and immunofluorescence and coimmunoprecipitation were used to identify putative signalling pathways. We found that skin erythema and histopathological alterations, as well as elevated proinflammatory factors (IL-1ß, IL-6, TNFα, CXCL2) and CAMP, were significantly ameliorated by colchicine treatment in LL37-induced rosacea-like mice. In addition, colchicine reduced the colocalization of TLR2 and neutrophils and the formation of neutrophil extracellular trap networks (NET) in mouse lesions. In neutrophils, colchicine markedly reduced TLR2 agonist-induced inflammatory biomarker expression, NET formation, and ROS production. Moreover, we found that LL37 could bind to TLR2 upon activation of TLR2 in neutrophils. Importantly, colchicine could repress the combination of TLR2 and LL37 in vivo. Finally, bioinformatics methods further validated the key molecules of neutrophil-related inflammation in rosacea, which is consistent with our experimental findings. Collectively, colchicine ameliorated rosacea-like dermatitis by regulating the neutrophil immune response activated by the TLR2 pathway, indicating that it could be an effective therapeutic option for patients with rosacea.

The alteration of mucosal bile acid profile is associated with nerve growth factor expression in mast cells and bowel symptoms in diarrhea-predominant irritable bowel syndrome.

Mucosal bile acid (BA) profile is still unestablished in diarrhea-predominant irritable bowel syndrome (IBS-D). The aim of this study was to explore colonic mucosal BAs and their associations with mucosal mast cell (MMC)-derived nerve growth factor (NGF) and bowel symptoms in IBS-D. Colonic mucosal biopsies from 36 IBS-D patients and 35 healthy controls (HCs) were obtained for targeted BA profiling. MMC count and the expression of NGF and tight junction proteins (TJPs) were examined. We found that colonic mucosal BA profile was altered in the IBS-D cohort. The proportion of primary BAs was significantly higher and that of secondary BAs was lower in IBS-D patients. According to the 90th percentile of total mucosal BA content of HCs, IBS-D patients were divided into BA-H (n = 7, 19.4%) and BA-L (n = 29, 80.6%) subgroups. BA-H patients showed significantly higher total mucosal BA content compared to BA-L subgroup and HCs. The mucosal content of 11 BA metabolites significantly increased in BA-H subgroup, e.g. cholic acid (CA) and taurocholic acid (TCA). Moreover, BA-H patients displayed significantly elevated MMC count and NGF expression, with decreased expression of TJPs (claudin-1, junctional adhesion molecule-A and zonula occludens-1). Correlation analyses revealed that mucosal TCA content positively correlated with MMC count, MMC-derived NGF levels, and abdominal pain while negatively correlated with TJP expression. In conclusion, IBS-D patients showed an altered BA profile in the colonic mucosa. Approximately 20% of them exhibit elevated mucosal BA content, which may be associated with MMC-derived NGF signaling and bowel symptoms.

Mucosa-Associated Microbiota Dysbiosis in the Terminal Ileum Correlates With Bowel Symptoms in Diarrhea-Predominant Irritable Bowel Syndrome.

INTRODUCTION: The mucosa-associated microbiota (MAM) is not as frequently studied in diarrhea-predominant irritable bowel syndrome (IBS-D) compared with the fecal microbiota. In this study, we examined the MAM in the terminal ileum and its correlation with bowel symptoms in IBS-D. METHODS: Mucosal biopsies of the terminal ileum from 25 patients with IBS-D and 25 healthy controls were collected for 16S ribosomal RNA gene sequencing. Correlation analysis was performed. RESULTS: Compared with healthy controls, the MAM in the terminal ileum showed a decreased alpha diversity in the IBS-D cohort (Chao1 and Shannon indexes, P < 0.05). And the overall MAM profile clustered separately into 2 groups (ADONIS [PERMANOVA, permutational multivariate analysis of variance], P < 0.05). At the phylum level, the relative abundance of Proteobacteria was significantly higher in the ileal MAM of patients with IBS-D while that of Firmicutes was significantly lower. At the genus level, the relative abundance of Pseudomonas was significantly higher in the IBS-D cohort, with lower Bacteroides and Ruminococcus . Moreover, 40.0% of patients with IBS-D had multiple small nodules (nodular lymphoid hyperplasia) on the mucosal surface of the terminal ileum, which indicated a low-grade inflammation. In patients with IBS-D with nodular lymphoid hyperplasia, the changes of Pseudomonas and Bacteroides were more overt. Correlation analysis revealed that the relative abundance of Pseudomonas positively correlated with abdominal pain and the severity of IBS. DISCUSSION: Patients with IBS-D showed a dysbiosis of MAM in the terminal ileum, which may be associated with bowel symptoms. Moreover, 40.0% of them displayed mucosal low-grade inflammation, with a more severe mucosal microbial disturbance.

ZBTB20 mediates stress-induced visceral hypersensitivity via activating the NF-κB/transient receptor potential channel pathway.

BACKGROUND: Psychological stress is a major trigger for visceral hypersensitivity (VH) in irritable bowel syndrome. The zinc finger protein ZBTB20 (ZBTB20) is implicated in somatic nociception via modulating transient receptor potential (TRP) channels, but its role in the development of VH is unclear. This study aimed to investigate the role of ZBTB20/TRP channel axis in stress-induced VH. METHODS: Rats were subjected to water avoidance stress (WAS) for 10 consecutive days. Small interfering RNA (siRNA) targeting ZBTB20 was intrathecally administered. Inhibitors of TRP channels, stress hormone receptors, and nuclear factor kappa-B (NF-κB) were administered. Visceromotor response to colorectal distension was recorded. Dorsal root ganglia (DRGs) were dissected for Western blot, coimmunoprecipitation, and chromatin immunoprecipitation. The DRG-derived neuron cell line was applied for specific research. KEY RESULTS: WAS-induced VH was suppressed by the inhibitor of TRPV1, TRPA1, or TRPM8, with enhanced expression of these channels in L6-S2 DRGs. The inhibitor of glucocorticoid receptor or ß2-adrenergic receptor counteracted WAS-induced VH and TRP channel expression. Concurrently, WAS-induced stress hormone-dependent ZBTB20 expression and NF-κB activation in DRGs. Intrathecally injected ZBTB20 siRNA or an NF-κB inhibitor repressed WAS-caused effect. In cultured DRG-derived neurons, stress hormones promoted nuclear translocation of ZBTB20, which preceded p65 nuclear translocation. And, ZBTB20 siRNA suppressed stress hormone-caused NF-κB activation. Finally, WAS enhanced p65 binding to the promoter of TRPV1, TRPA1, or TRPM8 in rat DRGs. CONCLUSIONS AND INFERENCES: ZBTB20 mediates stress-induced VH via activating NF-κB/TRP channel pathway in nociceptive sensory neurons.

Ex Vivo Evaluation of Combination Immunotherapy Using Tumor-Microenvironment-on-Chip.

Combination immunotherapy has emerged as a promising strategy to address the challenges associated with immune checkpoint inhibitor (ICI) therapy in breast cancer. The efficacy of combination immunotherapy hinges upon the intricate and dynamic nature of the tumor microenvironment (TME), characterized by cellular heterogeneity and molecular gradients. However, current methodologies for drug screening often fail to accurately replicate these complex conditions, resulting in limited predictive capacity for treatment outcomes. Here, a tumor-microenvironment-on-chip (TMoC), integrating a circulation system and ex vivo tissue culture with physiological oxygen and nutrient gradients, is described. This platform enables spatial infiltration of cytotoxic CD8+ T cells and their targeted attack on the tumor, while preserving the high complexity and heterogeneity of the TME. The TMoC is employed to assess the synergistic effect of five targeted therapy drugs and five chemotherapy drugs in combination with immunotherapy, demonstrating strong concordance between chip and animal model responses. The TMoC holds significant potential for advancing drug development and guiding clinical decision-making, as it offers valuable insights into the complex dynamics of the TME.

[Rectacted] miR­106b­5p promotes cell cycle progression of malignant melanoma by targeting PTEN.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the colony formation data shown in Fig. 2C on p. 333 had already appeared in previously published articles written by different authors at different research institutes. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 39: 331­337, 2018; DOI: 10.3892/or.2017.6099].

Lower limit characterization of segregation degree for large-size low-alloy steel.

Based on the original position statistic distribution analysis technique, the characterization method of segregation for large-size metal materials gives significant guidance to the research of material properties and production. However, random errors are inevitably brought into the calculation of segregation degree for materials characterization by the Spark Mapping Analysis for Large Sample (SMALS) technique, resulting in a misguide of the segregation degree. In this paper, we present the lower limit of segregation degree (Ds(L)) method to distinguish the random error from metal material segregation for large-size samples over the SMALS method. The random error of standard material in the 95% confidence interval was utilized as Ds(L) and the method has been applied for macro-segregation quantitative analysis. The precision correlation between Spark Atomic Emission Spectrometry (Spark-AES) and SMALS was established. Furthermore, the functional relationship between the Ds(L) and element content C can be obtained in the SMALS method. The Ds(L) method as the criterion can be used to not only characterize the minimum limit of the segregation degree but also the segregation existence for large-size samples. Applying to low-alloy steel can illustrate the effective performance of the Ds(L) method. Results on both spark mapping analysis and Spark-AES verify the substantial consistency.

Birth cohort changes in anxiety levels among primary school students in China during 1995-2019: A cross-temporal meta-analysis.

To investigate birth cohort changes in anxiety levels among primary school students in China, we conducted a cross-temporal meta-analysis of 126 studies (N = 109,957) reporting the anxiety levels among primary school students in China during 1995-2019 using the Mental Health Diagnostic Test (MHT); higher MHT scores indicated higher anxiety. The results showed that: (1) The MHT scores for five types of mental health problems (social anxiety, lonely tendency, physical symptoms, terror tendency, and impulsive tendency) and the total MHT score were significantly negatively correlated with the data-collection year, indicating that the anxiety levels among primary school students in China decreased over time. (2) The MHT score for learning anxiety was significantly positively correlated with the data-collection year, indicating that the learning anxiety levels of primary school students in China increased over time. (3) The overall MHT score did not show significant gender differences, but gender-wise varying trends were observed in the types considered.

Analysis of Ti-inclusions in high carbon chromium bearing steel by laser-induced breakdown spectroscopy.

The presence of Ti-inclusions has a significant impact on the fatigue life of bearing steel. Laser-induced breakdown spectroscopy (LIBS) is a useful tool for analyzing Ti-inclusions, despite the fact that the effective excitation area of LIBS is actually larger than the pre-set spot diameter. The area affected by the LIBS spot ranges from 150 µm to 376.6 µm. A new parameter L has been introduced for better understanding the characterization of Ti-inclusions detected in SEM-EDS and LIBS measurements, When the L threshold falls below the value of 188.3 µm, the SEM-EDS and LIBS data are obtained from the same Ti-inclusion. The study demonstrates that there is a linear relationship between LIBS intensity and Ti-inclusions area, which was tested both theoretically and practically. The analysis of six samples of rolling GCr15 bearing steel with a Cr element content of 1.5% shows that one regression line is enough for analyzing the same type of inclusion processed under the same conditions. This method can significantly reduce the workload and analysis time during the actual analysis process.

Stigma and Efficacy of Zhizhu Kuanzhong Capsules Versus Doxepin in the Treatment of Refractory Functional Dyspepsia: A Randomized Controlled Trial.

Background/Aims: Stigma related with antidepressants is prevalent in patients with functional dyspepsia. It affects medication compliance and efficacy. Herbal medicine acquired a deep-rooted cultural identity in relieving dyspeptic symptoms in Asians. The research was designed to compare the effectiveness of Zhizhu Kuanzhong capsules (ZZKZ) versus doxepin hydrochloride (doxepin) on alleviating stigma and medication nonadherence among patients with refractory FD (rFD). Methods: Patients with rFD from February 2021 to February 2022 were randomly allocated to receive either doxepin (n = 56) or ZZKZ (n = 57) combined with omeprazole for 4 weeks. Medication possession ratio (MPR), the disease- and medication-associated stigma were analyzed. The scales were utilized to assess dyspeptic symptoms (Leeds Dyspepsia Questionnaire) and psychological conditions (Generalized Anxiety Disorder Questionnaire and Patient Health Questionnaire). Results: The MPR values for ZZKZ were significantly higher than those for doxepin (P < 0.001). The stigma scores decreased in ZZKZ group while increased in doxepin group compared to baseline after treatment. The proportion of patients showing ZZKZ-associated stigma was significantly lower than doxepin-associated stigma (P < 0.001). The MPR values were negatively correlated with post-treatment stigma scores in both groups (P < 0.001). Dyspeptic symptoms and psychological condition were improved in both groups after treatment, with no significant difference on post-treatment Leeds Dyspepsia Questionnaire, Generalized Anxiety Disorder Questionnaire, or Patient Health Questionnaire scores between 2 groups. Conclusion: ZZKZ is superior to doxepin in alleviating stigma and medication non-adherence, with comparable efficacy in improving dyspeptic symptoms and psychological condition of patients with rFD.

Psychological trauma, posttraumatic stress disorder and trauma-related depression: A mini-review.

There are various types of traumatic stimuli, such as catastrophic events like wars, natural calamities like earthquakes, and personal trauma from physical and psychological neglect or abuse and sexual abuse. Traumatic events can be divided into type I and type II trauma, and their impacts on individuals depend not only on the severity and duration of the traumas but also on individuals' self-evaluation of the traumatic events. Individual stress reactions to trauma include posttraumatic stress disorder (PTSD), complex PTSD and trauma-related depression. Trauma-related depression is a reactive depression with unclear pathology, and depression occurring due to trauma in the childhood has gained increasing attention, because it has persisted for a long time and does not respond to conventional antidepressants but shows good or partial response to psychotherapy, which is similar to the pattern observed for PTSD. Because trauma-related depression is associated with high risk of suicide and is chronic with a propensity to relapse, it is necessary to explore its pathogenesis and therapeutic strategy.