High-protein high-konjac glucomannan diets changed glucose and lipid metabolism by modulating colonic microflora and bile acid profiles in healthy mouse models.

High protein and fiber diets are becoming increasingly popular for weight loss; however, the benefits or risks of high protein and fiber diets with a normal calorie level for healthy individuals still need to be elucidated. In this study, we explored the role and mechanisms of long-term high protein and/or konjac glucomannan diets on the metabolic health of healthy mouse models. We found that high konjac glucomannan contents improved the glucose tolerance of mice and both high protein and high konjac glucomannan contents improved the serum lipid profile but increased the TNF-α levels. In the liver, high dietary protein contents reduced the expression of the FASN gene related to fatty acid synthesis. Interactions of dietary protein and fiber were shown in the signaling pathways related to lipid and glucose metabolism of the liver and the inflammatory status of the colon, wherein the high protein and high konjac glucomannan diet downregulated the expression of the SREBF1 and FXR genes in the liver and downregulated the expression of TNF-α genes in the colon compared to the high protein diet. High konjac glucomannan contents reduced the colonic secondary bile acid levels including DCA and LCA; this was largely associated with the changed microbiota profile and also contributed to improved lipid and glucose homeostasis. In conclusion, high protein diets improved lipid homeostasis and were not a risk to metabolic health, while high fiber diets improved glucose and lipid homeostasis by modulating colonic microbiota and bile acid profiles, and a high protein diet supplemented with konjac glucomannan might improve hepatic lipid homeostasis and colonic inflammation in healthy mouse models through long-term intervention.

Surveillance for adverse events following immunization with DTaP-containing combination vaccines in Linping, China, 2019-2022.

Background: The DTaP-Hib and DTaP-IPV/Hib combination vaccine can be used as a substitute for the diphtheria, tetanus, and acellular pertussis combined vaccine (DTaP). We aimed to evaluate the safety of multi-component vaccines containing DTaP by analyzing the reporting rates and characteristics of adverse events following immunization (AEFIs) in Linping District during the years 2019 to 2022. Methods: We obtained data of AEFI and vaccination from the National AEFI Surveillance System of China and Zhejiang Municipal Immunization Information Management System, respectively, during 2019-2022 for a descriptive, epidemiological analysis. Results: The total number of AEFI reported following vaccinations with DTaP-containing combination vaccines was 802 in Linping District from 2019 to 2022. The overall reporting rates of AEFIs following DTaP, DTaP-Hib, and DTaP-IPV/Hib vaccinations were 445.72 (537 cases), 536.29 (45 cases), and 306.13 (220 cases) per 100,000 doses in Linping District from 2019 to 2022, respectively. Only one case of a serious AEFI following DTaP vaccination, with a reporting rate of 0.83 per 100,000 doses. The composition ratio of vaccine product-related reactions for DTaP, DTaP-Hib, and DTaP-IPV/Hib were 99.81, 97.78, and 100.00%, respectively. The composition ratio of coincidental events for DTaP and DTaP-Hib were 0.19 and 2.22%, respectively. The reporting rates of total AEFIs for DTaP-IPV/Hib were lower than for DTaP. The reporting rate of local induration for DTaP-Hib was lower than for DTaP, and the reporting rates of local redness & swelling and local induration for DTaP-IPV/Hib were both lower than for DTaP. DTaP-IPV/Hib had a higher proportion of AEFIs in first quarter compared to DTaP. The reporting rate after the second dose of DTaP-Hib was higher than that of DTaP, and the reporting rates of AEFIs after the first dose and third dose of DTaP-IPV/Hib were lower than DTaP. Conclusion: The reported AEFIs to multi-component vaccines containing DTaP components during 2019-2022 in Linping District were mainly mild vaccine reactions. DTaP-containing combination vaccines demonstrated a good safety profile.

Disruption of mitochondrial energy metabolism is a putative pathogenesis of Diamond-Blackfan anemia.

Energy metabolism in the context of erythropoiesis and related diseases remains largely unexplored. Here, we developed a primary cell model by differentiating hematopoietic stem progenitor cells toward the erythroid lineage and suppressing the mitochondrial oxidative phosphorylation (OXPHOS) pathway. OXPHOS suppression led to differentiation failure of erythroid progenitors and defects in ribosome biogenesis. Ran GTPase-activating protein 1 (RanGAP1) was identified as a target of mitochondrial OXPHOS for ribosomal defects during erythropoiesis. Overexpression of RanGAP1 largely alleviated erythroid defects resulting from OXPHOS suppression. Coenzyme Q10, an activator of OXPHOS, largely rescued erythroid defects and increased RanGAP1 expression. Patients with Diamond-Blackfan anemia (DBA) exhibited OXPHOS suppression and a concomitant suppression of ribosome biogenesis. RNA-seq analysis implied that the substantial mutation (approximately 10%) in OXPHOS genes accounts for OXPHOS suppression in these patients. Conclusively, OXPHOS disruption and the associated disruptive mitochondrial energy metabolism are linked to the pathogenesis of DBA.

Correlation between triglyceride glucose index and collateral circulation formation in patients with chronic total occlusion of coronary arteries in different glucose metabolic states.

BACKGROUND: To investigate the correlation between triglyceride glucose index (TyG) and collateral circulation in patients with chronic total occlusion (CTO) of coronary arteries in different glucose metabolic states. METHODS: A total of 681 patients who underwent coronary angiography between January 2020 and December 2021 to determine the presence of CTO lesions in at least one major coronary artery were retrospectively included in this study. Patients were categorized into a group with poor collateral circulation formation (Rentrop grade 0-1, n = 205) and a group with good collateral circulation formation (Rentrop grade 2-3, n = 476) according to the Rentrop scale. They were also categorized according to their glucose metabolism status: normal glucose regulation (NGR) (n = 139), prediabetes mellitus (Pre-DM) (n = 218), and diabetes mellitus (DM) (n = 324). Correlation between TyG index and collateral circulation formation was analyzed by logistic regression analysis and receiver operating characteristic (ROC) curves. RESULTS: Among patients with CTO, TyG index was significantly higher in the group with poor collateral circulation formation than in the group with good collateral circulation formation. Logistic regression analysis showed that TyG index was an independent risk factor for poor collateral circulation formation (OR 5.104, 95% CI 3.323-7.839, P < 0.001). The accuracy of TyG index in predicting collateral circulation formation was evaluated by the ROC curve, which had an area under the curve of 0.779 (95% CI 0.738-0.820, P < 0.001). The restrictive cubic spline curves showed that the risk of poor collateral circulation formation in the Pre-DM and DM groups was initially flat and finally increased rapidly, except for the NGR group. TyG index was significantly associated with an increased risk of poor collateral circulation formation in the Pre-DM and DM groups. CONCLUSIONS: TyG index was significantly associated with the risk of poor collateral circulation formation in patients with CTO, especially those with Pre-DM and DM.

Crop DNA extraction with lab-made magnetic nanoparticles.

Molecular breeding methods, such as marker-assisted selection and genomic selection, require high-throughput and cost-effective methods for isolating genomic DNA from plants, specifically from crop tissue or seed with high polysaccharides, lipids, and proteins. A quick and inexpensive high-throughput method for isolating genomic DNA from seed and leaf tissue from multiple crops was tested with a DNA isolation method that combines CTAB extraction buffer and lab-made SA-coated magnetic nanoparticles. This method is capable of isolating quality genomic DNA from leaf tissue and seeds in less than 2 hours with fewer steps than a standard CTAB extraction method. The yield of the genomic DNA was 582-729 ng per 5 leaf discs or 216-1869 ng per seed in soybean, 2.92-62.6 ng per 5 leaf discs or 78.9-219 ng per seed in wheat, and 30.9-35.4 ng per 5 leaf discs in maize. The isolated DNA was tested with multiple molecular breeding methods and was found to be of sufficient quality and quantity for PCR and targeted genotyping by sequencing methods such as molecular inversion probes (MIPs). The combination of SA-coated magnetic nanoparticles and CTAB extraction buffer is a fast, simple, and environmentally friendly, high-throughput method for both leaf tissues and seed(s) DNA preparation at low cost per sample. The DNA obtained from this method can be deployed in applied breeding programs for marker-assisted selection or genomic selection.

Effect of Tooth Mobility on the Accuracy of Conventional Impressions: A Pilot Study.

PURPOSE: To study the influence of tooth mobility on the accuracy of conventional impressions. MATERIALS AND METHODS: In total, 10 patients with mobile anterior teeth and 10 healthy patients were treated with conventional impressions and intraoral digital impressions. The digital impression group was recorded as standard data, the mobile teeth group was recorded as the experimental group, and the healthy anterior teeth group was recorded as the control group. We imported digital impression and irreversible hydrocolloid impression files into Geomagic Wrap and marked reference points to execute N-point alignment, then we recorded the coordinates. Paired-samples t test was used to analyze whether the point coordinates of mobile teeth were statistically significant (a = .05). One-way ANOVA was used to analyze whether there was a relationship between coordinate differences and tooth mobility in the distal, coronal, and buccal directions (a = .05). RESULTS: In the buccal and coronal directions, the difference was statistically significant between the conventional and digital impression groups. In the buccal direction, the accuracy differences of I-degree and II-degree mobile teeth were 0.149 mm and 0.401 mm, respectively. In the coronal direction, the differences were 0.128 mm and 0.233 mm, respectively. Meanwhile, ANOVA analysis showed that there was a relationship between point coordinate difference and tooth mobility in the buccal and coronal directions. CONCLUSIONS: Conventional impressions can influence the accuracy of mobile tooth impressions. Therefore, digital impressions should be adopted for mobile teeth impressions.

TCOD: an integrated resource for tropical crops.

Tropical crops are vital for tropical agriculture, with resource scarcity, functional diversity and extensive market demand, providing considerable economic benefits for the world's tropical agriculture-producing countries. The rapid development of sequencing technology has promoted a milestone in tropical crop research, resulting in the generation of massive amount of data, which urgently needs an effective platform for data integration and sharing. However, the existing databases cannot fully satisfy researchers' requirements due to the relatively limited integration level and untimely update. Here, we present the Tropical Crop Omics Database (TCOD, https://ngdc.cncb.ac.cn/tcod), a comprehensive multi-omics data platform for tropical crops. TCOD integrates diverse omics data from 15 species, encompassing 34 chromosome-level de novo assemblies, 1 255 004 genes with functional annotations, 282 436 992 unique variants from 2048 WGS samples, 88 transcriptomic profiles from 1997 RNA-Seq samples and 13 381 germplasm items. Additionally, TCOD not only employs genes as a bridge to interconnect multi-omics data, enabling cross-species comparisons based on homology relationships, but also offers user-friendly online tools for efficient data mining and visualization. In short, TCOD integrates multi-species, multi-omics data and online tools, which will facilitate the research on genomic selective breeding and trait biology of tropical crops.

OBIA: An Open Biomedical Imaging Archive.

With the development of artificial intelligence (AI) technologies, biomedical imaging data play an important role in scientific research and clinical application, but the available resources are limited. Here we present Open Biomedical Imaging Archive (OBIA), a repository for archiving biomedical imaging and related clinical data. OBIA adopts five data objects (Collection, Individual, Study, Series, and Image) for data organization, and accepts the submission of biomedical images of multiple modalities, organs, and diseases. In order to protect personal privacy, OBIA has formulated a unified de-identification and quality control process. In addition, OBIA provides friendly and intuitive web interfaces for data submission, browsing, and retrieval, as well as image retrieval. As of September 2023, OBIA has housed data for a total of 937 individuals, 4136 studies, 24,701 series, and 1,938,309 images covering 9 modalities and 30 anatomical sites. Collectively, OBIA provides a reliable platform for biomedical imaging data management and offers free open access to all publicly available data to support research activities throughout the world. OBIA can be accessed at https://ngdc.cncb.ac.cn/obia.

An Overview of Image Generation of Industrial Surface Defects.

Intelligent defect detection technology combined with deep learning has gained widespread attention in recent years. However, the small number, and diverse and random nature, of defects on industrial surfaces pose a significant challenge to deep learning-based methods. Generating defect images can effectively solve this problem. This paper investigates and summarises traditional defect generation and deep learning-based methods. It analyses the various advantages and disadvantages of these methods and establishes a benchmark through classical adversarial networks and diffusion models. The performance of these methods in generating defect images is analysed through various indices. This paper discusses the existing methods, highlights the shortcomings and challenges in the field of defect image generation, and proposes future research directions. Finally, the paper concludes with a summary.

A 2-component blend of coconut oil-derived fatty acids as an oviposition deterrent against Drosophila suzukii (Drosophilidae: Diptera).

Coconut free fatty acid (CFFA), a mixture of 8 fatty acids derived from coconut oil, is an effective repellent and deterrent against a broad array of hematophagous insects. In this study, we evaluated the oviposition deterrent activity of CFFA on spotted-wing drosophila (SWD; Drosophila suzukii), a destructive invasive pest of berries and cherries, and identified bioactive key-deterrent compounds. In laboratory 2-choice tests, CFFA deterred SWD oviposition in a dose-dependent manner with the greatest reduction (99%) observed at a 20-mg dose compared with solvent control. In a field test, raspberries treated with 20-mg CFFA received 64% fewer SWD eggs than raspberries treated with the solvent control. In subsequent laboratory bioassays, 2 of CFFA components, caprylic and capric acids, significantly reduced SWD oviposition by themselves, while 6 other components had no effect. In choice and no-choice assays, we found that a blend of caprylic acid and capric acid, at equivalent concentrations and ratio as in CFFA, was as effective as CFFA, while caprylic acid or capric acid individually were not as effective as the 2-component blend or CFFA at equivalent concentrations, indicating the 2 compounds as the key oviposition deterrent components for SWD. The blend was also as effective as CFFA for other nontarget drosophilid species in the field. Given that CFFA compounds are generally regarded as safe for humans, CFFA and its bioactive components have potential application in sustainably reducing SWD damage in commercial fruit operations, thereby reducing the sole reliance on insecticides.

Coconut fatty acids exhibit strong repellency and week-long efficacy against several urban pest arthropods of the southwestern United States.

BACKGROUND: The southwestern United States is home to a variety of arthropods including Turkestan cockroaches, Blatta lateralis (Walker); hematophagous kissing bugs, Tritoma rubida (Uhler); and Arizona bark scorpions, Centruroides sculpturatus Ewing. These arthropods cause medical concern when they become established around homes and/or invade indoors. Traditionally, the management of these pests has relied primarily on the use of chemical insecticides; however, they offer poor prospects for control owing to their lack of efficacy as well as the effects of insecticides on humans and the environment. Botanical repellents are an option that has not been fully investigated for the management of these pests. Here, we investigated the behavioral responses of common urban pests of the southwestern USA to recently discovered coconut fatty acids (CFAs), to establish the potential use of these compounds as repellents. RESULTS: Fresh residues of CFA mixture (CFAm) and their constituents caprylic acid, capric acid, capric acid methyl ester, lauric acid, and lauric acid methyl ester, tested at a concentration of 1 mg cm-2 , strongly repelled all arthropods. The repellent activity of CFAm lasted for at least 7 days, and the addition of lavender oil, used as an odor-masking agent, did not decrease this effect. Concentrations of CFAm ten times lower (0.1 mg cm-2 ) still repelled Turkestan cockroaches, and concentrations 100 times lower (0.01 mg cm-2 ) repelled T. rubida and scorpions. CONCLUSIONS: CFAm and some of their constituents are efficacious, economical, and logistically feasible for inclusion in integrated pest management programs for these important urban pests of the southwestern USA. © 2023 Society of Chemical Industry.

Effects of cell deformability and adhesion strength on dynamic cell seeding: Cell-scale investigation via mesoscopic modeling.

The flow of cell suspension through a porous scaffold is a common process in dynamic cell seeding, which determines the initial distribution of cells for constructing tissue-engineered grafts. Physical insights into the transport and adhesion behaviors of cells in this process are of great significance to the precise control of cell density and its distribution in the scaffold. Revealing of dynamic mechanisms underlying these cell behaviors through experiments is still difficult. The numerical approach therefore plays an important role in such studies. However, existing studies have mostly focused on external factors (e.g., flow conditions and scaffold architecture) but ignored the intrinsic biomechanical properties of cells as well as their associated effects. The present work utilized a well-established mesoscopic model to simulate the dynamic cell seeding within a porous scaffold, based on which a thorough investigation of the effects of cell deformability and cell-scaffold adhesion strength on the seeding process was carried out. The results show that the increase in either the stiffness or the bond strength of cells would augment the firm-adhesion rate and thus enhance seeding efficiency. In comparison to cell deformability, bond strength seems to play a more dominant role. Especially in the cases with weak bond strength, remarkable losses of seeding efficiency and distribution uniformity are observed. Noteworthily, it is found that both the firm-adhesion rate and the seeding efficiency are quantiatively related to the adhesion strength which is measured as the detachment force, suggesting a straightforward way to estimate the seeding outcome.

McAN: a novel computational algorithm and platform for constructing and visualizing haplotype networks.

Haplotype networks are graphs used to represent evolutionary relationships between a set of taxa and are characterized by intuitiveness in analyzing genealogical relationships of closely related genomes. We here propose a novel algorithm termed McAN that considers mutation spectrum history (mutations in ancestry haplotype should be contained in descendant haplotype), node size (corresponding to sample count for a given node) and sampling time when constructing haplotype network. We show that McAN is two orders of magnitude faster than state-of-the-art algorithms without losing accuracy, making it suitable for analysis of a large number of sequences. Based on our algorithm, we developed an online web server and offline tool for haplotype network construction, community lineage determination, and interactive network visualization. We demonstrate that McAN is highly suitable for analyzing and visualizing massive genomic data and is helpful to enhance the understanding of genome evolution. Availability: Source code is written in C/C++ and available at https://github.com/Theory-Lun/McAN and https://ngdc.cncb.ac.cn/biocode/tools/BT007301 under the MIT license. Web server is available at https://ngdc.cncb.ac.cn/bit/hapnet/. SARS-CoV-2 dataset are available at https://ngdc.cncb.ac.cn/ncov/. Contact: songshh@big.ac.cn (Song S), zhaowm@big.ac.cn (Zhao W), baoym@big.ac.cn (Bao Y), zhangzhang@big.ac.cn (Zhang Z), ybxue@big.ac.cn (Xue Y).

Coconut oil derived five-component synthetic oviposition deterrent for oriental fruit fly, Bactrocera dorsalis.

BACKGROUND: Bactrocera dorsalis, oriental fruit fly (OFF), is one of the most destructive agricultural pests. Although bait sprays can effectively control OFF, resistance development has been a concern. We evaluated the oviposition deterrent activity of coconut free fatty acids (CFFA), a mixture of eight coconut oil-derived fatty acids known to repel hematophagous insects and deter their feeding and oviposition, against OFF females. RESULTS: In laboratory 72-h two-choice assays using guava-juice infused-agar as an oviposition substrate, CFFA deterred OFF oviposition in a dose-dependent manner with the greatest reduction of 87% at 20 mg dose compared to the control. When the eight CFFA components were tested individually, four compounds (caprylic, capric, oleic, and linoleic acids) significantly reduced OFF oviposition ('negative-compounds'), two (lauric and myristic acids) had no effect ('neutral-compounds'), and two (palmitic and stearic acids) stimulated OFF oviposition ('positive-compounds'). In two-choice tests, the 'negative-compounds' blend failed to elicit the same level of oviposition reduction as CFFA at equivalent concentrations found in CFFA. Adding the two 'neutral-compounds' recovered the oviposition deterrence similar to CFFA. Subsequent subtraction tests showed that four 'negative-compounds' plus lauric acid was as effective as CFFA in reducing OFF oviposition in guava-juice agar. This five-component key-deterrent blend also reduced OFF oviposition by 95 and 72% on papaya and tomato fruit, respectively. CONCLUSION: CFFA acts as an oviposition deterrent for OFF. Given that CFFA compounds are generally regarded as safe for humans and the environment, CFFA and its bioactive components have potential use in behavioral control strategies against OFF. © 2023 Society of Chemical Industry. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Efficacy and safety of early chest tube removal after selective pulmonary resection with high-output drainage: A systematic review and meta-analysis.

BACKGROUND: There is controversy over the drainage threshold for removal of chest tubes in the absence of significant air leakage after selective pulmonary resection. METHODS: A comprehensive search of online databases (PubMed, Web of Science, Embase, Cochrane Library, Scopus, Ovid, Elsevier, Ebsco, and Wiley) and clinical trial registries (WHO-ICTRP and ClinicalTrials.gov) was performed to investigate the efficacy and safety of early chest tube removal with high-output drainage. Primary outcome (postoperative hospital day) and secondary outcomes (30-day complications, rate of thoracentesis, and chest tube placement) were extracted and synthesized. Subgroup analysis, meta-regression, and sensitivity analysis were used to explore the potential heterogeneity. Study quality was assessed with the Newcastle-Ottawa Scale, and evidence was graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment by the online GRADEpro Guideline Development Tool. RESULTS: Six cohort studies with a total of 1262 patients were included in the final analysis. The postoperative hospital stay in the high-output group was significantly shorter than in the conventional treatment group (weighted mean difference: -1.34 [-2.34 to -0.34] day, P = .009). While there was no significant difference between 2 groups in 30-day complications (relative ratio [RR]: 0.92 [0.77-1.11], P = .38), the rate of thoracentesis (RR: 1.93 [0.63-5.88], P = .25) and the rate of chest tube placement (RR: 1.00 [0.37-2.70], P = .99). According to the sensitivity analysis, the relative impacts of the 2 groups had already stabilized. Subgroup analysis revealed that postoperative hospital stay was modified by Newcastle-Ottawa Scale score. The online GRADEpro Guideline Development Tool presented very low quality of evidence for the available data. CONCLUSIONS: This meta-analysis revealed that it is feasible and safe to remove a chest tube with high-output drainage after pulmonary resection for selected patients.

A push-pull strategy to suppress stable fly (Diptera: Muscidae) attacks on pasture cattle via a coconut oil fatty acid repellent formulation and traps with m-cresol lures.

BACKGROUND: Stable flies [Stomoxys calcitrans (L.)] are economically important pests of cattle and other livestock. As an alternative to conventional insecticides, we tested a push-pull management strategy using a coconut oil fatty acid repellent formulation and an attractant-added stable fly trap. RESULTS: In our field trials we found that weekly applications of a push-pull strategy can reduce stable fly populations on cattle as well as a standard insecticide (permethrin). We also found that the efficacy periods of the push-pull and permethrin treatments following on-animal application were equivalent. Traps with an attractant lure used as the pull component of the push-pull strategy captured sufficient numbers of stable flies to reduce on-animal numbers by an estimated 17-21%. CONCLUSIONS: This is the first proof-of-concept field trial demonstrating the effectiveness of a push-pull strategy using a coconut oil fatty acid-based repellent formulation and traps with an attractant lure to manage stable flies on pasture cattle. Also notable is that the push-pull strategy had an efficacy period equivalent to that of a standard, conventional insecticide under field conditions. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Efficacy Evaluation of Medium-Chain Fatty Acids as Skin and Spatial Repellents Against Aedes aegypti (Diptera:Culicidae) Mosquitoes.

Fatty acids derived from natural oils are considered as perspective products for adoption as repellents. Fatty acids derived from coconut oil have shown promise as repellents. This study consisted of an olfactometer evaluation of new formulations containing medium-chain fatty acids for spatial repellency and an in laboratory arm-in cage study for contact repellency against Aedes aegypti L. mosquitoes. Six formulations each of capric acid and lauric acid were evaluated for spatial repellency. These formulations contained 0.28-10% of either capric acid or lauric acid as the active ingredients in a consumer friendly skin care formulation. Base formula without fatty acids was evaluated as control in spatial repellency evaluation. For the arm-in cage evaluations, six formulations of capric acid, one base formulation, and a 7% N,N-diethyl-m-toluamide (DEET) product were tested for contact repellency. For contact repellency, United States Department of Agriculture (USDA) standard repellent test cages were used to determine the complete protection time (CPT) of the different formulated repellents. Among all capric acid formulations tested, the concentration of 2.25% (wt) indicated the best level of spatial repellency, but not significantly different from other concentrations. None of the lauric acid concentrations showed any level of spatial repellency. In the arm-in-cage evaluations, the highest contact repellency resulted from 4.5% capric acid, which was significantly higher than 7% DEET and base formula.

The relationship between mean platelet volume lymphocyte ratio and collateral circulation in patients with chronic total coronary occlusion.

Objective: To correlate mean platelet volume lymphocyte ratio (MPVLR) and coronary collateral circulation (CCC) in patients with chronic total occlusion (CTO). Materials and methods: A total of 643 patients who were hospitalized at a single large academic medical center from January 2020 to October 2021 and had CTO lesions in at least one major coronary artery confirmed by coronary angiography were retrospectively analyzed. Patients were divided according to the Rentrop criteria into poorly formed CCC (Rentrop grade 0-1, n = 235) and well-formed CCC (Rentrop grade 2-3, n = 408) groups. Mean platelet volume lymphocyte ratio (MPVLR) was calculated from routine laboratory data (MPV divided by lymphocyte count). The clinical data of the two groups were compared, and relationships between MPVLR and CCC formation were analyzed. Results: The MPVLR of patients with poorly formed CCC was significantly higher than that of patients with well-formed CCC (7.82 ± 3.80 vs. 4.84 ± 1.42, P < 0.01). The prevalence of diabetes mellitus and C-reactive protein levels were significantly higher in the poor CCC group than in the good CCC group (P < 0.01), while the proportions of patients with CTO or multivessel lesions in the right coronary artery were significantly lower in the poor CCC group than in the good CCC group (P < 0.01). Multivariate logistic regression analysis identified MPVLR (OR: 2.101, 95% CI: 1.840-2.399, P < 0.01), C-reactive protein level (OR: 1.036, 95% CI: 1.008-1.064, P < 0.05), a history of diabetes mellitus (OR: 2.355, 95% CI: 1.532-3.621, P < 0.01), and right coronary CTO ratio (OR: 0.313, 95% CI: 0.202-0.485, P < 0.01) as independent risk factors for CCC formation. The area under the ROC curve of MPVLR for predicting poorly formed CCC was 0.82 (95% CI: 0.784-0.855, P < 0.01), the best cut-off point was 6.02 and the sensitivity and specificity of MPVLR for predicting poorly formed CCC were 72.3 and 82.4%, respectively. Conclusion: In patients with coronary CTO, MPVLR was negatively correlated with CCC and a high MPVLR level was an independent predictor of poorly formed CCC.

Transmembrane Protein ANTXR1 Regulates γ-Globin Expression by Targeting the Wnt/ß-Catenin Signaling Pathway.

Reactivation of fetal hemoglobin (HbF, α2γ2) alleviates clinical symptoms in patients with ß-thalassemia and sickle cell disease, although the regulatory mechanisms of γ-globin expression have not yet been fully elucidated. Recent studies found that interfering with the expression of the membrane protein ANTXR1 gene upregulated γ-globin levels. However, the exact mechanism by which ANTXR1 regulates γ-globin levels remains unclear. Our study showed that overexpression and knockdown of ANTXR1 in K562, cord blood CD34+, and HUDEP-2 cells decreased and increased γ-globin expression, respectively. ANTXR1 regulates the reactivation of fetal hemoglobin (HbF, α2γ2) in K562, cord blood CD34+, and adult peripheral blood CD34+ cells through interaction with LRP6 to promote the nuclear entry of ß-catenin and activate the Wnt/ß-catenin signaling pathway. The overexpression or knockdown of ANTXR1 on γ-globin and Wnt/ß-catenin signaling in K562 cells was reversed by the inhibitor XAV939 and the activator LiCl, respectively, where XAV939 inhibits the transcription of ß-catenin in the Wnt pathway, but LiCl inhibits GSK3-ß. We also showed that the binding ability of the rank4 site in the transcriptional regulatory region of the SOX6 gene to c-Jun was significantly increased after overexpression of ANTXR1 in K562 cells. SOX6 protein expression was increased significantly after overexpression of the c-Jun gene, indicating that the transcription factor c-Jun initiated the transcription of SOX6, thereby silencing γ-globin. Our findings may provide a new intervention target for the treatment of ß-hemoglobinopathies.