Address model mismatch and defocus in FZA lensless imaging via model-driven CycleGAN.

Mask-based lensless imaging systems suffer from model mismatch and defocus. In this Letter, we propose a model-driven CycleGAN, MDGAN, to reconstruct objects within a long distance. MDGAN includes two translation cycles for objects and measurements respectively, each consisting of a forward propagation and a backward reconstruction module. The backward module resembles the Wiener-U-Net, and the forward module consists of the estimated image formation model of a Fresnel zone aperture camera (FZACam), followed by CNN to compensate for the model mismatch. By imposing cycle consistency, the backward module can adaptively match the actual depth-varying imaging process. We demonstrate that MDGAN based on either a simulated or calibrated imaging model produces a higher-quality image compared to existing methods. Thus, it can be applied to other mask-based systems.

The global burden, trends and cross-country inequalities of female breast and gynaecologic cancers: A population based study.

OBJECTIVE: To analyse the global burden, trends and cross-country inequalities of female breast and gynaecologic cancers (FeBGCs). DESIGN: Population-Based Study. SETTING: Data sourced from the Global Burden of Disease Study 2019. POPULATION: Individuals diagnosed with FeBGCs. METHODS: Age-standardised mortality rates (ASMRs), age-standardised Disability-Adjusted Life Years (DALYs) rates (ASDRs) and their 95% uncertainty interval (UI) described the burden. Estimated annual percentage changes (EAPCs) and their confidence interval (CI) of age-standardised rates (ASRs) illustrated trends. Social inequalities were quantified using the Slope Index of Inequality (SII) and Concentration Index. MAIN OUTCOME MEASURES: The main outcome measures were the burden of FeBGCs and the trends in its inequalities over time. RESULTS: In 2019, the ASDRs per 100 000 females were as follows: breast cancer: 473.83 (95% UI: 437.30-510.51), cervical cancer: 210.64 (95% UI: 177.67-234.85), ovarian cancer: 124.68 (95% UI: 109.13-138.67) and uterine cancer: 210.64 (95% UI: 177.67-234.85). The trends per year from 1990 to 2019 were expressed as EAPCs of ASDRs and these: for Breast cancer: -0.51 (95% CI: -0.57 to -0.45); Cervical cancer: -0.95 (95% CI: -0.99 to -0.89); Ovarian cancer: -0.08 (95% CI: -0.12 to -0.04); and Uterine cancer: -0.84 (95% CI: -0.93 to -0.75). In the Social Inequalities Analysis (1990-2019) the SII changed from 689.26 to 607.08 for Breast, from -226.66 to -239.92 for cervical, from 222.45 to 228.83 for ovarian and from 74.61 to 103.58 for uterine cancer. The concentration index values ranged from 0.2 to 0.4. CONCLUSIONS: The burden of FeBGCs worldwide showed a downward trend from 1990 to 2019. Countries or regions with higher Socio-demographic Index (SDI) bear a higher DALYs burden of breast, ovarian and uterine cancers, while those with lower SDI bear a heavier burden of cervical cancer. These inequalities increased over time.

Dietary capsaicin attenuates cardiac injury after myocardial infarction in type 2 diabetic mice by inhibiting ferroptosis through activation of TRPV1 and Nrf2/HMOX1 pathway.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a major 21st-century epidemic. T2DM elevates the risk of myocardial infarction and heart failure while also reducinges survival rates. Recently Ferroptosis has been found to be involved in the development of various cardiovascular diseases. TRPV1 is also a potential therapeutic target for cardioprotection. This study explores whether capsaicin, a transient receptor potential vanilloid receptor 1 (TRPV1) agonist, can prevent diabetic myocardial infarction-induced injury by inhibiting ferroptosis. METHODS: T2DM model was induced by high-fat diet (HFD) feeding combined with streptozocin (STZ) injections, and the diabetic mice were treated with capsaicin(0.015 %) in their food. Myocardial infarction model was established as well. Mouse' general characteristics, cardiac function, and morphological histology were observed and analyzed. RNA-seq was used to investigate the possible mechanism of injury in AC16 cardiomyocytes cultured with high glucose and hypoxia. In addition, the potential mechanism of capsaicin against injury was further investigated in AC16 cardiomyocytes cultured with high glucose and hypoxia. RESULTS: The RNA-seq analysis revealed that ferroptosis was associated with cell death induced by high-glucose in combination with hypoxia, and CAP treatment could effectively inhibit ferroptosis to enhance cell survival. In vivo studies demonstrated that CAP treatment significantly improved post-MI cardiac function, attenuated myocardial inflammation and fibrosis. Furthermore, it was observed that CAP reduced ferroptosis levels by activating TRPV1 in the heart, upregulating Nrf2 expression, promoting Nrf2 nuclear translocation and increasing the expression of the Nrf2 downstream molecule Heme oxygenase-1 (HMOX1). CONCLUSIONS: Dietary capsaicin may inhibit cardiomyocyte ferroptosis through activation of myocardial TRPV1 and Nrf2/HMOX1 signaling pathway, which in turn exerts a protective effect on the myocardium after myocardial infarction in type 2 diabetic mice.

Algorithm of spatial-temporal simulation for environment-strain interactions in strain-strain consortia based on resource competition mechanism.

Interaction simulation for co-culture systems is important for optimizing culture conditions and improving yields. For industrial production, the environment significantly affects the spatial-temporal microbial interactions. However, the current research on polymicrobial interactions mainly focuses on interaction patterns among strains, and neglects the environment influence. Based on the resource competition relationship between two strains, this research set up the modules of cellular physicochemical properties, nutrient uptake and metabolite release, cellular survival, cell swimming and substrate diffusion, and investigated the spatial-temporal strain-environment interactions through module coupling and data mining. Furthermore, in an Escherichia coli-Saccharomyces cerevisiae consortium, the total net reproduction rate decreased as glucose was consumed. E. coli gradually dominated favorable positions due to its higher glucose utilization capacity, reaching 100 % abundance with a competitive strength of 0.86 for glucose. Conversely, S. cerevisiae decreased to 0 % abundance with a competitive strength of 0.14. The simulation results of environment influence on strain competitiveness showed that inoculation ratio and dissolved oxygen strongly influenced strain competitiveness. Specifically, strain competitiveness increased with higher inoculation ratio, whereas E. coli competitiveness increased as dissolved oxygen increased, in contrast to S. cerevisiae. On the other hand, substrate diffusion condition, micronutrients and toxins had minimal influence on strain competitiveness. This method offers a straightforward procedure without featured downscaling and provides novel insights into polymicrobial interaction simulation.

Umbilical Cord Blood-Derived Cells Can Reconstruct Hematopoiesis in an Aplastic Anemia Animal Model.

Objectives: To explore the efficacy and the mechanism of the umbilical cord-derived cells combined with cyclosporine A (CsA) in treating aplastic anemia (AA) in mice. Methods: Immune-mediated AA model mice were treated with CsA + UC mesenchymal stem cells (UC-MSC), CsA + umbilical cord blood regulatory T cells (UCB-Treg), UC-MSC, UCB-Treg, CsA alone, or blank control, respectively (n = 9 mice/group). CsA and the cell infusion was administered on d0. Routine peripheral blood testing was performed once weekly; bone marrow colony culture, bone marrow cell flow cytometry, peripheral blood T cell subsets, and serum inflammatory cytokines tests were performed on d14. Transcriptome sequencing was performed for cells from CsA + UC-MSC, CsA + UCB-Treg, and CsA groups to detect the possible related genes. Gene function cluster and signal pathway enrichment analysis were also performed. Results: Blank control mice died due to pancytopenia within 21 days, whereas mice in other groups survived for >28 days. On d14, the CsA + UC-MSC and CsA + UCB-Treg groups had higher white blood cell (WBC) counts than the other groups (p < 0.05), along with higher burst-forming unit (BFU) and colony-forming unit-granulocyte, macrophage (CFU-GM) counts (p < 0.01). The CsA + UC-MSC group had the highest BFU count (p < 0.01). The CsA + UC-MSC and CsA + UCB-Treg groups exhibited the highest bone marrow CD34+ cell proportion (9.68% ± 1.35% and 8.17% ± 0.53%, respectively; p < 0.01). Tumor necrosis factor (TNF)-α and interleukin (IL)-2 levels in the CsA + UC-MSC group (p < 0.05) and TNF-α, interleukin-2, and interferon (INF)-γ levels in the CsA + UC-Treg group (p < 0.01) were lower than those in the CsA group. Compared with CsA treatment, CsA + UC-MSC significantly downregulated the histone methylation pathway (p < 0.05), whereas CsA + UCB-Treg significantly upregulated energy metabolism processes (p < 0.05). Treatment with CsA + UC-MSC upregulated superoxide dismutase activity compared with CsA + UCB-Treg treatment. Conclusions: Adding UC-MSC or UCB-Treg to CsA markedly enhanced the reconstruction of hematopoiesis in AA mice, with UC-MSC eliciting greater efficiency than UCB-Treg. Accordingly, the addition of these cells could further improve immune abnormalities.

MSEmbGAN: Multi-Stitch Embroidery Synthesis via Region-Aware Texture Generation.

Convolutional neural networks (CNNs) are widely used for embroidery feature synthesis from images. However, they are still unable to predict diverse stitch types, which makes it difficult for the CNNs to effectively extract stitch features. In this paper, we propose a multi-stitch embroidery generative adversarial network (MSEmbGAN) that uses a region-aware texture generation sub-network to predict diverse embroidery features from images. To the best of our knowledge, our work is the first CNN-based generative adversarial network to succeed in this task. Our region-aware texture generation sub-network detects multiple regions in the input image using a stitchclassifierandgeneratesastitchtextureforeachregionbasedonitsshapefeatures.Wealsoproposeacolorizationnetworkwitha color feature extractor, which helps achieve full image color consistency by requiring the color attributes of the output to closely resemble the input image. Because of the current lack of labeled embroidery image datasets, we provide a new multi-stitch embroidery dataset that is annotated with three single-stitch types and one multi-stitch type. Our dataset, which includes more than 30K high-quality multistitch embroidery images, more than 13K aligned content-embroidered images, and more than 17K unaligned images, is currently the largest embroidery dataset accessible, as far as we know. Quantitative and qualitative experimental results, including a qualitative user study, show that our MSEmbGAN outperforms current state-of-the-artembroiderysynthesisandstyle-transfermethodsonallevaluation indicators. Our demo and dataset sample can be found on the website https://csai.wtu.edu.cn/TVCG01/index.html.

A Case of Primary Hepatic Mucosa-Associated Lymphoid Tissue Lymphoma in a Patient With Primary Biliary Cholangitis and Hashimoto's Thyroiditis.

Mucosa-associated lymphoid tissue (MALT) lymphoma is a low-grade malignant lymphoproliferative disease, representing a low percentage of newly diagnosed lymphoma cases. Although its exact cause is still unclear, it is commonly associated with infections or autoimmune diseases. The stomach is the most frequent site for MALT lymphoma, with primary hepatic MALT lymphoma being exceptionally rare. Cases of primary hepatic MALT lymphoma often coincide with viral hepatitis. In this report, we present a case of primary hepatic MALT lymphoma in a patient with no history of hepatitis but complicated by primary biliary cholangitis (PBC) and Hashimoto's thyroiditis.

Effect of glycosylation, acylation and pyranylation at cyanidin C-ring on its interaction with vitamin C in apple juice beverage matrix.

BACKGROUND: Synchronous degradation between anthocyanin and vitamin C was found in fruit and vegetable juice matrices. To investigate whether the C-ring of anthocyanin is the key site of this interaction, cyanidin with four different C-ring modifications (3-glucosylation, 3,5-diglucosylation, 6″-malonylation, pyranylation) was added to vitamin C-containing apple juice, and the changes of anthocyanin retention, vitamin C retention, color, antioxidative activity and differential metabolites were analyzed. RESULTS: The anthocyanin retention was in the order of pyranylation >6″-malonylation >3,5-diglucosylation >3-glucosylation. The vitamin C retention was in the order of 6″-malonylation > pyranylation >3,5-diglucosylation >3-glucosylation. The order of color stability was the same as that of anthocyanin retention, and the order of antioxidative activity was opposite to that of vitamin C retention. The results showed that modification at the C-ring limited the activity of anthocyanin, and suggested that the C-ring was one of the key sites for anthocyanin and vitamin C interaction. The shared differential metabolite of all apple juice matrices added with different anthocyanins was trans-hinokiresinol, which was likely generated from anthocyanin skeleton reacted with certain compounds in apple juice. CONCLUSION: This study showed that modification of the anthocyanin C-ring could affect the anthocyanin and vitamin C interaction to some extent, which provided valuable insights for the application of anthocyanin C-ring modification in shelf-life quality control of typical fruit and vegetable beverages with the coexistence of anthocyanin and vitamin C. © 2024 Society of Chemical Industry.

An untargeted comparative metabolomics analysis of infants with and without late-onset breast milk jaundice.

BACKGROUND: Late-onset breast milk jaundice (LBMJ) is a common form of hyperbilirubinemia, which can result in serious complications for newborns with persistently high bilirubin levels. The aim of this study was to investigate the differences in fecal metabolites between breastfed infants with and without LBMJ in order to elucidate potential biological mechanisms. METHODS: Biological samples were collected from 12 infants with LBMJ and 12 healthy individuals. Ultra-high performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF/MS) was utilized for non-targeted determination of fecal metabolites. Principal components analysis (PCA), cluster analysis, and differential metabolite analysis were performed in both positive ion mode and negative ion mode for the two groups. Additionally, the KEGG database was employed to comprehensively analyze the pathways of differential metabolites. RESULTS: There were no significant differences in maternal and neonatal demographic characteristics between the two groups (p > 0.05). The results of PCA and cluster heat map analysis in both modes showed that there were significant differences in metabolites between the two groups. Among 751 differential metabolites (DMs) detected in positive ion mode, 720 were up-regulated in the case group while 31 were down-regulated. In negative ion mode, 1891 DMs were detected, including 817 up-regulated metabolites and 1074 down-regulated metabolites in the case group. Analysis of differential metabolic pathways showed that the DMs of the two groups were mainly annotated and enriched in Biotin metabolism, N-Glycan biosynthesis, Taurine and hypotaurine metabolism, Pyrimidine metabolism, and Pentose and glucuronate interconversions. CONCLUSION: Significant differences exist in fecal metabolites between LBMJ infants and healthy controls. The study of differential metabolic pathways provides insights into the mechanism of LBMJ.

Rational optimization of glycoprotein E (gE)-encoding mRNA for improved Varicella-zoster Virus mRNA vaccine development.

The past decades have seen increasingly rapid advances in the field of mRNA technology and its successful applications in prophylactic vaccine development [1,2]. Recently, we reported on the development of a novel Varicella-zoster virus (VZV) mRNA vaccine (named as ZOSAL) that contains mRNAs encoding for full-length gE immunogen (623 aa) encapsulated into a novel lipid nanoparticle (LNP) system [3]. In mice and rhesus macaques, ZOSAL induced superior virus-specific immunity over licensed subunit vaccine Shingrix, which potentiated the power of mRNA platform in next-generation VZV vaccine development [3].

Mediation analysis for TNF-α as a mediator between multiple metal exposure and kidney function.

The association between metal mixtures and kidney function has been reported. However, reports on the mechanism of metal toxicity were limited. Oxidative stress was reported as a possible cause. This study aimed to determine the association between of kidney function and metals, such as arsenic (As), cadmium (Cd), cobalt (Co), copper (Cu), lead (Pb), selenium (Se), and zinc (Zn), and to explore the possible mediating role of tumor necrosis factor alpha (TNF-α) between metal toxicity and kidney function. In this study, we recruited 421 adults from a health examination. The concentration of blood metals was analyzed using inductively coupled plasma mass spectrometry. We used linear regression models to assess the association between metals and TNF-α. Then, mediation analysis was applied to investigate the relationship between metal exposure, TNF-α, and kidney function. In univariate linear regression, blood As, Cd, Co, Cu, Pb, and Zn levels significantly increased TNF-α and decreased kidney function. Higher blood As and Pb levels significantly increased TNF-α in multivariable linear regressions after adjusting for covariates. We found that blood levels of As (coefficients = -0.021, p = 0.011), Pb (coefficients = -0.060, p < 0.001), and Zn (coefficients = -0.230, p < 0.001) showed a significant negative association with eGFR in the multiple-metal model. Furthermore, mediation analysis showed that TNF-α mediated 41.7 %, 38.8 %, and 20.8 % of blood Cd, As and Pb, respectively. Among the essential elements, TNF-α mediated 24.5 %, 21.5 % and 19.9 % in the effects of blood Co, Cu, and Zn on kidney function, respectively. TNF-α, acting as a mediator, accounted for 20.1 % of the contribution between the WQS score of metal mixtures and the eGFR (p < 0.001). This study suggested that TNF-α may be a persuasive pathway mediating the association between metals and kidney function. Inflammation and kidney injury could be the underlying mechanisms of metal exposure. However, there is still a need to clarify the biochemical mechanism in follow-up studies.

Lipidomics reveals ceramide biomarkers for detecting central precocious puberty in girls.

BACKGROUND: Pubertal timing is modulated by complex interactions between the pituitary and gonadal sex steroid hormones. Evidence indicates that sphingolipids are involved in the biosynthesis of steroid hormones at multiple levels. METHOD: This study recruited adolescent female patients from pubertal and pediatric endocrine clinics in Northern and Southern Taiwan from the Taiwan Puberty Longitudinal Study. A total of 112 plasma samples (22 healthy control, 29 peripheral precocious puberty (PPP), and 61 CPP samples) were collected. We extracted lipids from the plasma samples using the modified Folch method. The un-targeted ultrahigh-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was employed for the lipid analysis. RESULTS: We identified sphingolipid-linked metabolites, including Cer(18:0/15:0), Cer(18:1/16:0), and Cer(18:1/26:0) as candidate biomarkers for distinguishing girls with CPP from the control group by using an excellent discrimination model (AUC = 0.964). Moreover, Cer(18:0/22:0) and Cer(d18:0/18:1) were identified as potential biomarkers of PPP, with an AUC value of 0.938. Furthermore, CerP(18:1/18:0) was identified as the sole candidate biomarker capable of differentiating CPP from PPP. CONCLUSIONS: The biomarkers identified in this study can facilitate the accurate detection of CPP in girls, provide insights into lipid-linked pathophysiology, and present a novel method of monitoring the progression of this disorder.

Single-belt vs. split-belt treadmill symmetry training: is there a perfect choice for gait rehabilitation post-stroke?

Post-stroke gait asymmetry leads to inefficient gait and a higher fall risk, often causing limited home and community ambulation. Two types of treadmills are typically used for training focused on symmetry: split-belt and single belt treadmills, but there is no consensus on which treadmill is superior to improve gait symmetry in individuals with stroke. To comprehensively determine which intervention is superior, we considered multiple spatial and temporal gait parameters (step length, stride time, swing time, and stance time) and their symmetries. Ten individuals with stroke underwent a single session of split-belt treadmill training and single belt treadmill training on separate days. The changes in step length, stride time, swing time, stance time and their respective symmetries were compared to investigate which training improves both spatiotemporal gait parameters and symmetries immediately after the intervention and after 5 min of rest. Both types of treadmill training immediately increased gait velocity (0.08 m/s faster) and shorter step length (4.15 cm longer). However, split-belt treadmill training was more effective at improving step length symmetry (improved by 27.3%) without sacrificing gait velocity or step length. However, this step length symmetry effect diminished after a 5-min rest period. Split-belt treadmill training may have some advantages over single belt treadmill training, when targeting step length symmetry. Future research should focus on comparing the long-term effects of these two types of training and examining the duration of the observed effects to provide clinically applicable information.

Protective signature of xanthohumol on cognitive function of APP/PS1 mice: a urine metabolomics approach by age.

Alzheimer's disease (AD) has an increasing prevalence, complicated pathogenesis and no effective cure. Emerging evidences show that flavonoid compounds such as xanthohumol (Xn) could play an important role as a dietary supplement or traditional Chinese herbal medicine in the management of diseases such as AD. This study aims to analyze the target molecules of Xn in the prevention and treatment of AD, and its potential mechanism from the perspective of metabolites. APP/PS1 mice 2- and 6-months old were treated with Xn for 3 months, respectively, the younger animals to test for AD-like brain disease prevention and the older animals to address therapeutic effects on the disease. Memantine (Mem) was selected as positive control. Behavioral tests were performed to assess the course of cognitive function. Urine samples were collected and analyzed by high-performance liquid chromatography (HPLC) with tandem mass spectrometry (MS/MS) coupled with online Compound Discoverer software. Morris Water Maze (MWM) tests showed that Xn, like Mem, had a therapeutic but not a preventive effect on cognitive impairment. The expression levels of urinary metabolites appeared to show an opposite trend at different stages of Xn treatment, downregulated in the prevention phase while upregulated in the therapy phase. In addition, the metabolic mechanisms of Xn during preventive treatment were also different from that during therapeutic treatment. The signaling pathways metabolites nordiazepam and genistein were specifically regulated by Xn but not by Mem in the disease prevention stage. The signaling pathway metabolite ascorbic acid was specifically regulated by Xn in the therapeutic stage. In conclusion, dietary treatment with Xn altered the urinary metabolite profile at different stages of administration in APP/PS1 mice. The identified potential endogenous metabolic biomarkers and signal pathways open new avenues to investigate the pathogenesis and treatment of AD.

Synthesis and properties of bio-based semi-aromatic heat-resistant copolymer polyamide 5T-co-6T.

Herein, poly(pentanediamine terephthalamide) (PA5T) homopolymer was synthesized via a salt-forming reaction+solid state polycondensation method using bio-based 1,5-pentanediamine and terephthalic acid as the primary raw materials. To address the issue of its narrower processing window, poly(hexamethylene terephthalamide)(PA6T), which also cannot be melt processed due to the processing window is negative, was introduced into its molecular chain to synthesize poly (pentanediamine/hexanediamine terephthaloyl) (PA5T-co-6T) copolymers. The structures were investigated by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance carbon spectroscopy (13C-NMR). Furthermore, the melting temperature, crystallization temperature, thermal stability, and crystal growth mode of the polymer were tested and analyzed using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and wide-angle x-ray diffraction (WAXD), respectively. The results demonstrate that the crystal growth mode gradually changes from three-dimensional spherical growth to two-dimensional disk-like or three-dimensional spherical growth with the increase of 6T chain segment content. Simultaneously, the crystallization temperature, melting temperature, and crystallization rate of the polymer all showed a trend of decreasing first and then increasing, which was due to the combined effects of the increase in the content of 6T chain segments on the molecular-chain structure and crystal structure of the polymer. Bio-based PA5T-co-6T has excellent heat resistance and a wider processing window than PA5T and PA6T, which possesses great application prospects in the fields of automotive, electronic appliances, and LED optics.

Binary ruthenium dioxide and nickel oxide ultrafine particles loaded on carbon nanotubes for high-stability oxygen evolution reaction at high current densities.

RuO2 is an efficient electrocatalyst for the oxygen evolution reaction (OER). However, during the OER process, RuO2 is prone to oxidation into Rux+ (x > 4), leading to its dissolution in the electrolyte and resulting in poor stability of RuO2. Here, we report a bicomponent electrocatalyst, NiO and RuO2 co-loaded on carbon nanotubes (RuO2/NiO/CNT). The results demonstrate that the introduction of NiO suppresses the over-oxidation of RuO2 during the OER process, not only inheriting the excellent catalytic performance of RuO2, but also significantly enhancing the stability of the catalyst for OER at high current densities. In contrast to RuO2/CNT, RuO2/NiO/CNT shows no significant change in activity after 150 h of OER at a current density of 100 mA cm-2. Density functional theory (DFT) calculations indicate that NiO transfers a large number of electrons to RuO2, thereby reducing the oxidation state of Ru. In conclusion, this study provides a detailed analysis of the phenomenon where low-valent metal oxides have the ability to enhance the stability of RuO2 catalysts.

Application of digital virtual simulated design in the prosthodontic rehabilitation of a child with a novel EDA mutation in ectodermal dysplasia: A clinical report.

This clinical report presents a 7-year-old patient with ectodermal dysplasia and a newly identified ectodysplasin A (EDA) gene mutation (c.965 T>C). A removable partial denture combined with a complete denture was provided after considering the relevant factors. Based on digital smile design, resin crowns were fabricated to restore the cone-shaped teeth esthetically. Facial scan parameters and maxillofacial landmark localization on cone beam computed tomography (CBCT) images were combined for the registration of jaw relation, and a Gothic arch was subsequently 3-dimensionally printed for verification. Ultimately, dentures with accurate occlusion and satisfactory retention were delivered for this young patient with inadequate bone volume and poor fit that markedly improved his esthetics and function.

LincR-PPP2R5C Deficiency Alleviates Airway Remodeling by Inhibiting Epithelial-Mesenchymal Transition Through the PP2A/TGF-ß1 Signaling Pathway in Chronic Experimental Allergic Asthma.

Airway remodeling is a key characteristic of allergic asthma. Epithelial-mesenchymal transition (EMT) induced by various factors, particularly transforming growth factor (TGF)-ß1, orchestrates airway remodeling. Protein phosphatase 2A (PP2A), an important serine-threonine phosphatase, is involved in TGF-ß1 production and EMT. Long noncoding RNAs (lncRNAs) have emerged as novel players in regulating EMT. Here, we aimed to explore the effects and mechanisms of action of lincR-PPP2R5C, a lncRNA that affects PP2A activity, on airway remodeling in a mouse model of chronic allergic asthma. LincR-PPP2R5C knockout (KO) alleviated inflammatory responses in house dust mite (HDM)-induced chronic allergic asthma. Moreover, airway remodeling and EMT were reduced in lung tissues of lincR-PPP2R5C KO mice. HDM extract induced EMT in airway epithelial cells, which was decreased following lincR-PPP2R5C KO. Mechanistically, lincR-PPP2R5C deficiency enhanced PP2A activity, which inhibited TGF-ß1 production in epithelial cells. In conclusion, lincR-PPP2R5C deficiency prevented HDM-induced airway remodeling in mice by reversing EMT, which was mediated by the PP2A/TGF-ß1 signaling pathway. Thus, lncRNAs, i.e., lincR-PPP2R5C, may be potential targets to prevent airway remodeling in allergic asthma.

Regulating Drug Release Performance of Acid-Triggered Dimeric Prodrug-Based Drug Self-Delivery System by Altering Its Aggregation Structure.

Dimeric prodrugs have been investigated intensely as carrier-free drug self-delivery systems (DSDSs) in recent decades, and their stimuli-responsive drug release has usually been controlled by the conjugations between the drug molecules, including the stimuli (pH or redox) and responsive sensitivity. Here, an acid-triggered dimeric prodrug of doxorubicin (DOX) was synthesized by conjugating two DOX molecules with an acid-labile ketal linker. It possessed high drug content near the pure drug, while the premature drug leakage in blood circulation was efficiently suppressed. Furthermore, its aggregation structures were controlled by fabricating nanomedicines via different approaches, such as fast precipitation and slow self-assembly, to regulate the drug release performance. Such findings are expected to enable better anti-tumor efficacy with the desired drug release rate, beyond the molecular structure of the dimeric prodrug.

Genome-wide CRISPR/Cas9 screen identifies SLC39A9 and PIK3C3 as crucial entry factors for Ebola virus infection.

The Ebola virus (EBOV) has emerged as a significant global health concern, notably during the 2013-2016 outbreak in West Africa. Despite the clinical approval of two EBOV antibody drugs, there is an urgent need for more diverse and effective antiviral drugs, along with comprehensive understanding of viral-host interactions. In this study, we harnessed a biologically contained EBOVΔVP30-EGFP cell culture model which could recapitulate the entire viral life cycle, to conduct a genome-wide CRISPR/Cas9 screen. Through this, we identified PIK3C3 (phosphatidylinositide 3-kinase) and SLC39A9 (zinc transporter) as crucial host factors for EBOV infection. Genetic depletion of SLC39A9 and PIK3C3 lead to reduction of EBOV entry, but not impact viral genome replication, suggesting that SLC39A9 and PIK3C3 act as entry factors, facilitating viral entry into host cells. Moreover, PIK3C3 kinase activity is indispensable for the internalization of EBOV virions, presumably through the regulation of endocytic and autophagic membrane traffic, which has been previously recognized as essential for EBOV internalization. Notably, our study demonstrated that PIK3C3 kinase inhibitor could effectively block EBOV infection, underscoring PIK3C3 as a promising drug target. Furthermore, biochemical analysis showed that recombinant SLC39A9 protein could directly bind viral GP protein, which further promotes the interaction of viral GP protein with cellular receptor NPC1. These findings suggests that SLC39A9 plays dual roles in EBOV entry. Initially, it serves as an attachment factor during the early entry phase by engaging with the viral GP protein. Subsequently, SLC39A9 functions an adaptor protein, facilitating the interaction between virions and the NPC1 receptor during the late entry phase, prior to cathepsin cleavage on the viral GP. In summary, this study offers novel insights into virus-host interactions, contributing valuable information for the development of new therapies against EBOV infection.