CPT-11 mitigates autoimmune diseases by suppressing effector T cells without affecting long-term anti-tumor immunity.

The incidence of autoimmune diseases has significantly increased over the past 20 years. Excessive host immunoreactions and disordered immunoregulation are at the core of the pathogenesis of autoimmune diseases. The traditional anti-tumor chemotherapy drug CPT-11 is associated with leukopenia. Considering that CPT-11 induces leukopenia, we believe that it is a promising drug for the control of autoimmune diseases. Here, we show that CPT-11 suppresses T cell proliferation and pro-inflammatory cytokine production in healthy C57BL/6 mice and in complete Freund's adjuvant-challenged mice. We found that CPT-11 effectively inhibited T cell proliferation and Th1 and Th17 cell differentiation by inhibiting glycolysis in T cells. We also assessed CPT-11 efficacy in treating autoimmune diseases in models of experimental autoimmune encephalomyelitis and psoriasis. Finally, we proved that treatment of autoimmune diseases with CPT-11 did not suppress long-term immune surveillance for cancer. Taken together, these results show that CPT-11 is a promising immunosuppressive drug for autoimmune disease treatment.

Chromatic correction for super multi-view 3D display based on diffraction theory.

The traditional analysis method for super multi-view 3D display based on geometric optics, which approximates the lenticular lenses as a series of pinhole structures, ignored the chromatic aberration. In this paper, the optimization method based on diffraction theory is proposed for super multi-view 3D display, where the wavefronts are evaluated accurately by the forward propagation method, and the chromatic aberration of the synthetic viewpoint image is reduced dramatically by the backward reconstruction optimization method (BROM). The optical experiment is performed to verify the feasibility of the method, which is consistent with numerical simulation results. It is proved that the proposed method simulates the physical propagation process of super multi-view 3D display and improves the reconstructed image quality. In the future, it can be used to achieve the super multi-view 3D light field technology with low crosstalk.

A New Method for Extracting Refined Sketches of Ancient Murals.

Mural paintings, as the main components of painted cultural relics, have essential research value and historical significance. Due to their age, murals are easily damaged. Obtaining intact sketches is the first step in the conservation and restoration of murals. However, sketch extraction often suffers from problems such as loss of details, too thick lines, or noise interference. To overcome these problems, a mural sketch extraction method based on image enhancement and edge detection is proposed. The experiments utilize Contrast Limited Adaptive Histogram Equalization (CLAHE) and bilateral filtering to enhance the mural images. This can enhance the edge features while suppressing the noise generated by over-enhancement. Finally, we extract the refined sketch of the mural using the Laplacian Edge with fine noise remover (FNR). The experimental results show that this method is superior to other methods in terms of visual effect and related indexes, and it can extract the complex line regions of the mural.

A novel framework for quantitative attribution of particulate matter pollution mitigation to natural and socioeconomic drivers.

Quantifying drivers contributing to air quality improvements is crucial for pollution prevention and optimizing local policies. Despite advances in machine learning for air quality analysis, their limited interpretability hinders attribution on global and local scales, vital for informed city management. Our study introduces an innovative framework quantifying socioeconomic and natural impacts on mitigation of particulate matter pollution in 31 Chinese major cities from 2014 to 2021. Two indices, formulated based on the additivity of Shapley additive explanations, are proposed to measure driver contributions globally and locally. Our analysis explores the self-contained and interactive effects of these drivers on particulate levels, pinpointing critical threshold values where these drivers trigger shifts in particulate matter levels. It is revealed that SO2, NOx, and dust emission reductions collectively account for 51.58 % and 51.96 % of PM2.5 and PM10 decreases at the global level. Moreover, our findings unveil a significant heterogeneity in driver contributions to pollutant mitigation across distinct cities, which can be instrumental in crafting location-specific policy recommendations.

Long noncoding RNA Malat1 protects against osteoporosis and bone metastasis.

MALAT1, one of the few highly conserved nuclear long noncoding RNAs (lncRNAs), is abundantly expressed in normal tissues. Previously, targeted inactivation and genetic rescue experiments identified MALAT1 as a suppressor of breast cancer lung metastasis. On the other hand, Malat1-knockout mice are viable and develop normally. On a quest to discover the fundamental roles of MALAT1 in physiological and pathological processes, we find that this lncRNA is downregulated during osteoclastogenesis in humans and mice. Remarkably, Malat1 deficiency in mice promotes osteoporosis and bone metastasis of melanoma and mammary tumor cells, which can be rescued by genetic add-back of Malat1. Mechanistically, Malat1 binds to Tead3 protein, a macrophage-osteoclast-specific Tead family member, blocking Tead3 from binding and activating Nfatc1, a master regulator of osteoclastogenesis, which results in the inhibition of Nfatc1-mediated gene transcription and osteoclast differentiation. Notably, single-cell transcriptome analysis of clinical bone samples reveals that reduced MALAT1 expression in pre-osteoclasts and osteoclasts is associated with osteoporosis and metastatic bone lesions. Altogether, these findings identify Malat1 as a lncRNA that protects against osteoporosis and bone metastasis.

The association of HBV infection and head and neck cancer: a systematic review and meta-analysis.

BACKGROUND: Hepatitis B virus (HBV) infections is an important public health problem worldwide and closely affect extrahepatic cancer. Several recent studies have investigated the relationship between HBV infection and head and neck cancer (HNC), but their findings were inconsistent.In order to address the limitations of small sample sizes, we conducted a meta-analysis to assess the association between HBV and HNC. METHODS: We systematically searched PubMed, Web of Science, Embase, Scopus, Cochrane Library, and China National Knowledge Infrastructure from inception to August 2023. Original articles published as a case-control or cohort study were included. HBV infection was identified by HBsAg, HBV DNA or ICD codes. Review articles, meeting abstracts, case reports, communications, editorials and letters were excluded, as were studies in a language other than English or Chinese. According to the MOOSE guidelines, frequencies reported for all dichotomous variables were extracted by two reviewers independently. Similarly, the outcomes of OR, RR or HR, and 95% CIs after adjusting for age and gender were collected. RESULTS: Thirteen relevant studies and 58,006 patients with HNC were included. Our analysis revealed a positive correlation between HBV and HNC (OR = 1.50; 95% CI: 1.28-1.77). After adjusting for age and gender, the similar result (OR = 1.30; 95% CI: 1.10-1.54) was obtained. Subgroup analysis further demonstrated a significant association between HBV infection and oral cancer (OR = 1.24; 95% CI: 1.05-1.47), as well as nasopharyngeal carcinoma (OR = 1.41; 95% CI: 1.26-1.58). However, due to the limited number of studies included, the statistical significance was not reached for cancer of the oropharynx (OR = 1.82; 95% CI: 0.66-5.05), hypopharynx (OR = 1.33; 95% CI: 0.88-2.00), and larynx (OR = 1.25; 95% CI: 0.69-2.24) after adjusting for age and gender. When excluding the interference of HIV/HCV, smoking and alcohol use, the final outcome (OR = 1.17; 95% CI: 1.01-1.35) got the same conclusion. CONCLUSIONS: Our study confirmed a positive relationship between HNC, specifically oral cancer and nasopharyngeal carcinoma, and HBV infection. However, further investigation is required at the molecular level to gather additional evidence in HNC.

Review on article of effects of tenofovir alafenamide and entecavir in chronic hepatitis B virus patients.

This letter comments on the article which reported that tenofovir alafenamide may increase blood lipid levels compared with entecavir in patients with chronic hepatitis B published on World J Hepatol 2023 August 27. We review the related research content, topic selection, methodology, conclusions, strengths and weaknesses of this article. And evaluate it in relation to other published relevant articles.

Developmental order, fibre caliber, and vascularization predict tract-wise declines: Testing retrogenesis and physiological predictions in white matter aging.

To understand the consistently observed spatial distribution of white-matter (WM) aging, developmentally driven theories of retrogenesis have gained traction, positing that the order WM development predicts declines. Regions that develop first are often expected to deteriorate the last, i.e. "last-in-first-out". Alternatively, regions which develop most rapidly may also decline most rapidly in aging, or the "gains-predict-loss" model. The validity of such theories remains uncertain, in part due to lack of clarity on the definition of developmental order. Our recent findings also suggest that WM degeneration may vary by physiological parameters such as perfusion. Furthermore, it is informative to link perfusion to fibre metabolic need, which varies with fibre size. Here we address the question of whether WM degeneration is determined by development trajectory or physiological state across both microstructural and perfusion measures using data drawn from the Human Connectome Project in Aging (HCP-A). Our results indicate that developmental order of tract myelination provides the strongest support for the retrogenesis hypothesis, with the last to complete myelination the first to decline. Moreover, higher mean axon diameter and lower macrovascular density are associated with lower degrees of WM degeneration across measures. Tract perfusion, in turn also tends to be higher and the arterial transit time longer for tracts that appear first. These findings suggest that WM degeneration in different tracts may be governed by their developmental trajectories and physiology, and ultimately influenced by each tract's metabolic demand.

Non-invasive fractional flow reserve derived from reduced-order coronary model and machine learning prediction of stenosis flow resistance.

BACKGROUND AND OBJECTIVE: Recently, computational fluid dynamics enables the non-invasive calculation of fractional flow reserve (FFR) based on 3D coronary model, but it is time-consuming. Currently, machine learning technique has emerged as an efficient and reliable approach for prediction, which allows saving a lot of analysis time. This study aimed at developing a simplified FFR prediction model for rapid and accurate assessment of functional significance of stenosis. METHODS: A reduced-order lumped parameter model (LPM) of coronary system and cardiovascular system was constructed for rapidly simulating coronary flow, in which a machine learning model was embedded for accurately predicting stenosis flow resistance at a given flow from anatomical features of stenosis. Importantly, the LPM was personalized in both structures and parameters according to coronary geometries from computed tomography angiography and physiological measurements such as blood pressure and cardiac output for personalized simulations of coronary pressure and flow. Coronary lesions with invasive FFR ≤ 0.80 were defined as hemodynamically significant. RESULTS: A total of 91 patients (93 lesions) who underwent invasive FFR were involved in FFR derived from machine learning (FFRML) calculation. Of the 93 lesions, 27 lesions (29.0%) showed lesion-specific ischemia. The average time of FFRML simulation was about 10 min. On a per-vessel basis, the FFRML and FFR were significantly correlated (r = 0.86, p < 0.001). The diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value were 91.4%, 92.6%, 90.9%, 80.6% and 96.8%, respectively. The area under the receiver-operating characteristic curve of FFRML was 0.984. CONCLUSION: In this selected cohort of patients, the FFRML improves the computational efficiency and ensures the accuracy. The favorable performance of FFRML approach greatly facilitates its potential application in detecting hemodynamically significant coronary stenosis in future routine clinical practice.

Prognostic Value of Holter Monitoring in Light Chain Amyloidosis.

(1) Background: To evaluate the predictive value of Holter monitoring for overall survival (OS) of patients with light chain amyloidosis (AL amyloidosis). (2) Methods: 137 patients with newly diagnosed AL amyloidosis who underwent Holter monitoring within 6 months of diagnosis were included. The primary outcome was OS. Landmark analysis was conducted at one-year follow-up. Independent predictors were determined using the log-rank test and multivariate Cox regression analysis. (3) Results: 131 (95.6%) patients received non-transplant therapy, and 32 (23.4%) underwent daratumumab-based chemotherapy. After a median follow-up of 20.3 months, 47 deaths occurred. Atrial tachycardia (AT), conduction delay, and non-sustained ventricular tachycardia (NSVT) were associated with poor OS one year beyond diagnosis in univariate analyses (patients with vs. without AT: 57.3% [95% confidence interval (CI): 47.2-67.4] vs. 81.0% (95% CI: 74.8-87.2), p = 0.039; patients with vs. without NSVT: 33.3% (95% CI: 8.5-58.1) vs. 75.3% (95% CI: 69.8-80.8), p = 0.024; patients with vs. without conduction delay: 41.7% (95% CI: 24.4-59.0) vs. 75.4% (95% CI: 69.7-81.1), p = 0.003]. AT [hazard ratio (HR): 2.6; 95% CI: 1.0-6.5; p = 0.049) and conduction delay (HR: 4.3; 95% CI: 1.3-14.3; p = 0.016) were independent predictors of OS after accounting for age and 2012 Mayo stage. (4) Conclusion: AT and conduction delay in Holter monitoring are independent predictors of poor OS one year beyond diagnosis in AL amyloidosis.

New Insights into YAP/TAZ-TEAD-Mediated Gene Regulation and Biological Processes in Cancer.

The Hippo pathway is conserved across species. Key mammalian Hippo pathway kinases, including MST1/2 and LATS1/2, inhibit cellular growth by inactivating the TEAD coactivators, YAP, and TAZ. Extensive research has illuminated the roles of Hippo signaling in cancer, development, and regeneration. Notably, dysregulation of Hippo pathway components not only contributes to tumor growth and metastasis, but also renders tumors resistant to therapies. This review delves into recent research on YAP/TAZ-TEAD-mediated gene regulation and biological processes in cancer. We focus on several key areas: newly identified molecular patterns of YAP/TAZ activation, emerging mechanisms that contribute to metastasis and cancer therapy resistance, unexpected roles in tumor suppression, and advances in therapeutic strategies targeting this pathway. Moreover, we provide an updated view of YAP/TAZ's biological functions, discuss ongoing controversies, and offer perspectives on specific debated topics in this rapidly evolving field.

Depth of field expansion method for integral imaging based on diffractive optical element and CNN.

In lens-based display systems, lens aberrations and depth of field (DoF) limitation often lead to blurring and distortion of reconstructed images; Meanwhile, expanding the display DoF will face a trade-off between horizontal resolution and axial resolution, restricting the achievement of high-resolution and large DoF three-dimensional (3D) displays. To overcome these constraints and enhance the DoF and resolution of reconstructed scenes, we propose a DoF expansion method based on diffractive optical element (DOE) optimization and image pre-correction through a convolutional neural network (CNN). This method applies DOE instead of the conventional lens and optimizes DOE phase distribution using the Adam algorithm, achieving depth-invariant and concentrated point spread function (PSF) distribution throughout the entire DoF range; Simultaneously, we utilize a CNN to pre-correct the original images and compensate for the image quality reduction introduced by the DOE. The proposed method is applied to a practical integral imaging system, we effectively extend the DoF of the DOE to 400 mm, leading to a high-resolution 3D display in multiple depth planes. To validate the effectiveness and practicality of the proposed method, we conduct numerical simulations and optical experiments.

Glutamine Ameliorates Liver Steatosis via Regulation of Glycolipid Metabolism and Gut Microbiota in High-Fat Diet-Induced Obese Mice.

Obesity and its associated conditions, such as nonalcoholic fatty liver disease (NAFLD), are risk factors for health. The aim of this study was to explore the effects of glutamine (Gln) on liver steatosis induced by a high-fat diet (HFD) and HEPG2 cells induced by oleic acid. Gln demonstrated a positive influence on hepatic homeostasis by suppressing acetyl CoA carboxylase (ACC) and fatty acid synthase (FAS) and promoting sirtuin 1 (SIRT1) expression while improving glucose metabolism by regulating serine/threonine protein kinase (AKT)/factor forkhead box O1 (FOXO1) signals in vivo and in vitro. Obese Gln-fed mice had higher colonic short-chain fatty acid (SCFA) contents and lower inflammation factor protein levels in the liver, HEPG2 cells, and jejunum. Gln-treated obese mice had an effective decrease in Firmicutes abundance. These findings indicate that Gln serves as a nutritional tool in managing obesity and related disorders.

Dual convolutional neural network for aberration pre-correction and image quality enhancement in integral imaging display.

This paper proposes a method that utilizes a dual neural network model to address the challenges posed by aberration in the integral imaging microlens array (MLA) and the degradation of 3D image quality. The approach involves a cascaded dual convolutional neural network (CNN) model designed to handle aberration pre-correction and image quality restoration tasks. By training these models end-to-end, the MLA aberration is corrected effectively and the image quality of integral imaging is enhanced. The feasibility of the proposed method is validated through simulations and optical experiments, using an optimized, high-quality pre-corrected element image array (EIA) as the image source for 3D display. The proposed method achieves high-quality integral imaging 3D display by alleviating the contradiction between MLA aberration and 3D image resolution reduction caused by system noise without introducing additional complexity to the display system.

Bibliometric analysis of medical and health research collaboration between China and ASEAN countries.

Objective: To reveal the characteristics, development trend and potential opportunities of China-ASEAN collaboration in the medical and health field based on bibliometrics. Methods: Scopus and International Center for the Study of Research Lab (ICSR Lab) was used to analyze the scale, collaboration network and distribution, impact of cooperative papers, collaboration dominance and evolution of the literature on China-ASEAN medical and health collaboration in the Scopus database from 1992 to 2022. Results: From 1992 to 2022, 19,764 articles on medical and health collaboration between China and ASEAN were filtered for analysis. The number of China-ASEAN collaborations has shown a clear upward trend over the years, indicating a gradually closer and improved collaboration relationship overall. The institutional collaboration network between China and ASEAN countries was obviously clustered, and the network connectivity was limited. The substantial differences between the median and mean values of citation impact of China-ASEAN medical and health research collaboration reflected that the collaboration was 'less' but 'better'. The dominance share of collaboration between China and the main ASEAN countries was fluctuating upward and has become more and more stable after 2004. Most of the China-ASEAN collaboration focused on their own characteristic research topics. In recent years, collaboration in infectious diseases and public health had expanded significantly, while other research topics had maintained in a complementary development trend. Conclusion: Collaboration between China and ASEAN in the medical and health field has exhibited a progressively closer relationship, and the trend of complementary research has remained stable. However, there are still areas of concern, including the limited scale of collaboration, narrow scope of participation and weak dominance.

Fiber-specific age-related differences in the white matter of healthy adults uncovered by fixel-based analysis.

Diffusion magnetic resonance imaging studies often investigate white matter (WM) microstructural degeneration in aging by probing WM regions that exhibit negative age associations of fractional anisotropy (FA). However, WM regions in which FA is unassociated with age are not necessarily "spared" in aging. Besides the confound of inter-participant heterogeneity, FA conflates all intravoxel fiber populations and does not allow the detection of individual fiber-specific age associations. In this study of 541 healthy adults aged 36-100 years, we use fixel-based analysis to investigate age associations among each "fixel" within a voxel, representing individual fiber populations. We find age associations of fixel-based measures that indicate age-related differences in individual fiber populations amid complex fiber architectures. Different crossing fiber populations exhibit different slopes of age associations. Our findings may provide evidence of selective degeneration of intravoxel WM fibers in aging, which does not necessarily manifest as a change in FA and therefore escapes notice if conventional voxel-based analyses are relied upon alone.

Role of Glucose Metabolic Reprogramming in Breast Cancer Progression and Drug Resistance.

The involvement of glucose metabolic reprogramming in breast cancer progression, metastasis, and therapy resistance has been increasingly appreciated. Studies in recent years have revealed molecular mechanisms by which glucose metabolic reprogramming regulates breast cancer. To date, despite a few metabolism-based drugs being tested in or en route to clinical trials, no drugs targeting glucose metabolism pathways have yet been approved to treat breast cancer. Here, we review the roles and mechanisms of action of glucose metabolic reprogramming in breast cancer progression and drug resistance. In addition, we summarize the currently available metabolic inhibitors targeting glucose metabolism and discuss the challenges and opportunities in targeting this pathway for breast cancer treatment.

Sufficient Phosphorus Enhances Resistance and Changes Accumulation of Lead in Chlamydomonas reinhardtii.

Phosphorus (P) is critical for algal growth and resistance to environmental stress. However, little is known about the effects of P supply on the lead (Pb) toxicity and accumulation in microalgae. We set up two P concentrations, 315 (PL ) and 3150 µg L-1 (PH ), in algal culture, and the responses of Chlamydomonas reinhardtii to various Pb treatments (0, 200, 500, 1000, 2000, and 5000 µg L-1 ) were investigated. Compared with the PL condition, PH promoted cell growth but reduced cellular respiration by approximately 50%. Moreover, PH alleviated damage to the photosynthetic system in algal cells after Pb stress. After exposure to 200-2000 µg L-1 Pb, higher Pb2+ concentrations and Pb removal were observed in the PL medium. However, under exposure to 5000 µg L-1 Pb, less Pb2+ was present but more Pb was removed by the algal cells in the PH medium. More P supply enhanced the secretion of extracellular fluorescent substances by C. reinhardtii. Transcriptomic analysis showed that genes associated with synthesis of phospholipids, tyrosine-like proteins, ferredoxin, and RuBisCO were up-regulated after Pb exposure. Together the findings of our study demonstrated the critical roles of P in Pb accumulation and resistance in C. reinhardtii. Environ Toxicol Chem 2023;42:1960-1970. © 2023 SETAC.