Vascular wall microenvironment: Endothelial cells original exosomes mediated melatonin-suppressed vascular calcification and vascular ageing in a m6A methylation dependent manner.

Vascular calcification and vascular ageing are "silent" diseases but are highly prevalent in patients with end stage renal failure and type 2 diabetes, as well as in the ageing population. Melatonin (MT) has been shown to induce cardiovascular protection effects. However, the role of MT on vascular calcification and ageing has not been well-identified. In this study, the aortic transcriptional landscape revealed clues for MT related cell-to-cell communication between endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) in vascular calcification and vascular ageing. Furthermore, we elucidated that it was exosomes that participate in the information transportation from ECs to VSMCs. The exosomes secreted from melatonin-treated ECs (MT-ECs-Exos) inhibited calcification and senescence of VSMCs. Mechanistically, miR-302d-5p was highly enriched in MT-ECs-Exos, while depletion of miR-302d-5p blocked the ability of MT-ECs-Exos to suppress VSMC calcification and senescence. Notably, Wnt3 was a bona fide target of miR-302d-5p and modulated VSMC calcification and senescence. Furthermore, we found that maturation of endothelial derived exosomal miR-302d-5p was promoted by WTAP in an N6-methyladenosine (m6A)-dependent manner. Interestingly, MT alleviated vascular calcification and ageing in 5/6-nephrectomy (5/6 NTP) mice, a chronic kidney disease (CKD) induced vascular calcification and vascular ageing mouse model. MT-ECs-Exos was absorbed by VSMCs in vivo and effectively prevented vascular calcification and ageing in 5/6 NTP mice. ECs-derived miR-302d-5p mediated MT induced anti-calcification and anti-ageing effects in 5/6 NTP mice. Our study suggests that MT-ECs-Exos alleviate vascular calcification and ageing through the miR-302d-5p/Wnt3 signaling pathway, dependent on m6A methylation.

MiRNA-132/212 encapsulated by adipose tissue-derived exosomes worsen atherosclerosis progression.

BACKGROUND: Visceral adipose tissue in individuals with obesity is an independent cardiovascular risk indicator. However, it remains unclear whether adipose tissue influences common cardiovascular diseases, such as atherosclerosis, through its secreted exosomes. METHODS: The exosomes secreted by adipose tissue from diet-induced obesity mice were isolated to examine their impact on the progression of atherosclerosis and the associated mechanism. Endothelial apoptosis and the proliferation and migration of vascular smooth muscle cells (VSMCs) within the atherosclerotic plaque were evaluated. Statistical significance was analyzed using GraphPad Prism 9.0 with appropriate statistical tests. RESULTS: We demonstrate that adipose tissue-derived exosomes (AT-EX) exacerbate atherosclerosis progression by promoting endothelial apoptosis, proliferation, and migration of VSMCs within the plaque in vivo. MicroRNA-132/212 (miR-132/212) was detected within AT-EX cargo. Mechanistically, miR-132/212-enriched AT-EX exacerbates palmitate acid-induced endothelial apoptosis via targeting G protein subunit alpha 12 and enhances platelet-derived growth factor type BB-induced VSMC proliferation and migration by targeting phosphatase and tensin homolog in vitro. Importantly, melatonin decreases exosomal miR-132/212 levels, thereby mitigating the pro-atherosclerotic impact of AT-EX. CONCLUSION: These data uncover the pathological mechanism by which adipose tissue-derived exosomes regulate the progression of atherosclerosis and identify miR-132/212 as potential diagnostic and therapeutic targets for atherosclerosis.

The association between the number of food kinds and risk of depression in U.S. adults.

BACKGROUND: The association between the number of food kinds and the risk of depression in adults was examined. METHODS: According to the inclusion and exclusion criteria, a total of 4593 adults were included in the study. The number of food kinds was collected via 24‒hour dietary recalls. Depression was assessed using the Patient Health Questionnaire‒9. Logistic regression and restricted cubic spline models were applied to assess the association between the number of food kinds and the risk of depression. RESULTS: This study included 4593 study participants, 451 of whom were diagnosed with depression. The revised advantage ratios (with corresponding confidence intervals) for the prevalence of depression among individuals in the fourth quartiles of the number of food kinds (Q4) in comparison to the lowest quartile (Q1) were determined to be 0.59 (0.36‒0.96), respectively. According to our subgroup analyses, the number of food kinds was negatively associated with the risk of depression in females, participants aged 18‒45 and 45‒65 years, and participants with a body mass index (BMI) of 25 to 24.9 kg/m2. According to our dose‒response analysis, the number of food kinds was linearly associated with the risk of depression (Pfor nonlinear=0.5896). CONCLUSION: The risk of depression exhibited a linear and negative correlation with the number of food kinds. The results indicated that a diversified diet was an effective nonpharmacological approach that deserved further generalization.

Efficient CRISPR-mediated genome editing can be initiated by embryonic injection but not by ovarian delivery in the beetle Tribolium castaneum.

The clustered regularly interspaced small palindromic repeats (CRISPR) / CRISPR-associated nuclease 9 (Cas9)-mediated gene editing technology has revolutionized the study of fundamental biological questions in various insects. Diverse approaches have been developed to deliver the single-guide RNA (sgRNA) and Cas9 to the nucleus of insect embryos or oocytes to achieve gene editing, including the predominant embryonic injection methods and alternative protocols through parental ovary delivery. However, a systematic comparative study of these approaches is limited, especially within a given insect. Here, we focused on revealing the detailed differences in CRISPR/Cas9-mediated gene editing between the embryo and ovary delivery methods in the beetle Tribolium castaneum, using the cardinal and tyrosine hydroxylase (TH) as reporter genes. We demonstrated that both genes could be efficiently edited by delivering Cas9/sgRNA ribonucleoproteins to the embryos by microinjection, leading to the mutant phenotypes and indels in the target gene sites. Next, the Cas9/sgRNA complex, coupled with a nanocarrier called Branched Amphiphilic Peptide Capsules (BAPC), were delivered to the ovaries of parental females to examine the efficacy of BAPC-mediated gene editing. Although we observed that a small number of beetles' progeny targeting the cardinal exhibited the expected white-eye phenotype, unexpectedly, no target DNA indels were found following subsequent sequencing analysis. In addition, we adopted a novel approach termed "direct parental" CRISPR (DIPA-CRISPR). However, we still failed to find gene-editing events in the cardinal or TH gene-targeted insects. Our results indicate that the conventional embryonic injection of CRISPR is an effective method to initiate genome editing in T. castaneum. However, it is inefficient by the parental ovary delivery approach.

Half substitution of mineral N with fish protein hydrolysate enhancing microbial residue C and N storage and climate benefits under high straw residue return.

The widespread utilization of straw return was a popular practice straw disposal for highly intensive agriculture in China, which has brought about some negative impacts such as less time for straw complete biodegradation, aggravation of greenhouse gas evolution, and lower efficient of carbon accumulation. It was urgent to find an eco-friendly N-rich organic fertilizer instead of mineral N as activator to solve the above problems and lead a carbon accumulation in long tern management. Besides, microbial necromass was considered as a crucial contributor to persistent soil carbon (C) and nitrogen (N) pool. How organic fertilizer activators influence microbial residue under different amount of crop residues input remained unclear. Thus, soils incorporating moderate and high rate of rice straw residue with additions of half and full of organic activators (fish protein hydrolysates vs. manure) were incubated for measuring carbon dioxide (CO2) and nitrous oxide (N2O) emission, microbial community and necromass. It was found that soil CO2 emission was rapidest during the first 13 days of straw decomposition but remained lowest in the treatments of 50% mineral N substituted by fish protein hydrolysate. There were that 81%-89% of total CO2 release and 59%-65% of total N2O emission occurred within 60 days of incubation period, and bacterial community and nitrate positively affected soil CO2 and N2O release respectively. Straw incorporation amount and organic activator application interactively influenced soil CO2 emission but not affected soil N2O emission. After 360 days of incubation, the difference of bacterial necromass was noticeable but fungal necromass remained almost unaltered across all treatments. All treatments showed generally comparable contribution of microbial necromass N to the total N pool. The treatment of 50% mineral N substituted by fish protein hydrolysate under high rate of straw input (HSF50) promoted the highest proportion of microbial necromass C in soil organic C because of alleviating N limitation for microorganisms. Finally, HSF50 was recommended as an eco-friendly strategy for enhancing microbial necromass C and N storage and climate benefits in agroecosystems.

[Analysis on Spatial Variability of Hydrochemical Characteristics and Control Factors of Jinan Baotu Spring Area].

To understand the karst groundwater hydrochemical characteristics and ion sources of the Jinan Baotu Spring area, this study focused on the three functional zones as an indirect recharge area, direct recharge area, and discharge area. Through water sample collection and testing, the spatial variability of groundwater chemical characteristics in different functional zones and the formation mechanism were analyzed using hydrochemistry parameter statistics, multivariate statistics, self-organizing map, hydrochemistry graphical analysis, ion ratios, and other methods, guided by the theory of groundwater flow system and combined with regional physical geography and hydrogeological conditions. The results showed that： the groundwater of each functional zone was alkaline as is typical in the dissolution of carbonate minerals. Owing to the different groundwater runoff pathways, the variability of water chemistry parameters in different functional areas was obvious. The groundwater of the discharge area was recharged by both the direct recharge area and the indirect recharge area. The hydrochemistry type changed from HCO3-Ca type to HCO3·SO4-Ca type through the indirect recharge area to the discharge area. The presence of a small amount of gypsum dissolution within the aquifer generated Ca2+ and SO42-. The ions in groundwater mainly came from the dissolution and filtration of aquifer rock minerals, and at the same time, they were affected by cation exchange, mineral dissolution equilibrium, and the combined effects of human activities. The groundwater in the Baotu Spring area was greatly influenced by human activities, which to some extent affected the evolution of groundwater hydrochemistry in the spring area.

Electrochemical Dehydrogenative [3 + 2]/[5 + 2] Annulation of N-Arylacrylamides with γ,σ-Unsaturated Malonates via Direct C(sp3)-H/C(sp2)-H Functionalization.

Herein, we introduce an electrochemical dehydrogenative [3 + 2]/[5 + 2] annulation of easily available N-arylacrylamides with γ,σ-unsaturated malonates through C(sp3)-H/C(sp2)-H functionalization. The employment of inexpensive ferrocene as the redox catalyst allows access to diverse benzo[b]azepin-2-ones in moderate to excellent yields without stoichiometric oxidants. This protocol features broad substrate scope and excellent selectivity, and mechanistic studies indicated that the reaction proceeded through the oxidation of a C(sp3)-H bond to generate an alkyl radical, radical addition across the C═C bond, [3 + 2]/[5 + 2] annulations, and C(sp2)-H functionalization cascades.

Advancing Precise Syphilis Diagnosis: A Nontreponemal IgM Antibody-Based Model for Latent Syphilis Staging.

Purpose: Accurate differentiation between early and late latent syphilis stages is pivotal for patient management and treatment strategies. Nontreponemal IgM antibodies have shown potential in discriminating latent syphilis staging by differentiating syphilis activity. This study aimed to develop a predictive nomogram model for latent syphilis staging based on nontreponemal IgM antibodies. Patients and Methods: We explored the correlation between nontreponemal IgM antibodies and latent syphilis staging and developed a nomogram model to predict latent syphilis staging based on 352 latent syphilis patients. Model performance was assessed using AUC, calibration curve, Hosmer-Lemeshow χ2 statistics, C-index, Brier score, decision curve analysis, and clinical impact curve. Additionally, an external validation set was used to further assess the model's stability. Results: Nontreponemal IgM antibodies correlated with latent syphilis staging. The constructed model demonstrated a strong discriminative capability with an AUC of 0.743. The calibration curve displayed a strong fit, key statistics including Hosmer-Lemeshow χ² at 2.440 (P=0.486), a C-index score of 0.743, and a Brier score of 0.054, all suggesting favorable model calibration performance. Decision curve analysis and clinical impact curve highlighted the model's robust clinical applicability. The external validation set yielded an AUC of 0.776, Hosmer-Lemeshow χ² statistics of 2.440 (P=0.486), a C-index score of 0.767, and a Brier score of 0.054, further underscored the reliability of the model. Conclusion: The nontreponemal IgM antibody-based predicted model could equip clinicians with a valuable tool for the precise staging of latent syphilis and enhancing clinical decision-making.

Patient compliance to sublingual immunotherapy for mite-induced allergic rhinitis: A retrospective study.

Background: Compliance to sublingual immunotherapy (SLIT) is generally low, resulting in reduced short- and long-term clinical efficacy. Compliance is a critical factor determining the success of allergic rhinitis (AR) treatment. Objective: To analyze the compliance of patients with house dust mite (HDM)-induced AR to SLIT and the impact of coronavirus disease 2019 (COVID-19) on compliance. Methods: The clinical data of 3117 patients with HDM-induced AR who started SLIT between July 2018 and April 2022 were retrospectively reviewed. We assessed the reasons for non-compliance and the changes in non-compliance during the COVID-19 pandemic compared to the pre-pandemic period. Results: Of 3117 patients, 507 (16.27%) patients (ages, 5-67 years) were identified as non-compliant. The most common reason for non-compliance was poor efficacy (27.22%). The non-compliance rate was highest during 24-36 months of SLIT (28.13%, 153/544), followed by 12-24 months (7.02%, 91/1296). Non-compliance was significantly higher in adolescents/adults than in children (P = 0.000). Although the generalized linear model analysis indicated that compliance was affected by the COVID-19 pandemic during 3-6 months of SLIT, the overall compliance to SLIT was not significantly affected by the pandemic, according to the Kaplan-Meier survival analysis. Conclusions: The non-compliance rate of SLIT in this study was low, and poor efficacy was the most common reason for non-compliance. The compliance of adolescents/adults was lower than that of children. The COVID-19 pandemic did not significantly impact compliance to SLIT, which is an appropriate strategy for the home treatment of AR patients during major public health events.

Laminarin-modulated osmium nanozymes with high substrate-affinity and selective peroxidase-like behavior engineered colorimetric assay for hydroxyl radical scavenging capacity estimation.

Hydroxyl radical (·OH) scavenging capacity (HOSC) estimation is essential for evaluating antioxidants, natural extracts, or drugs against clinical diseases. While nanozymes offer advantages in related applications, they still face limitations in activity and selectivity. In response, this work showcases the fabrication of laminarin-modulated osmium (laminarin-Os) nanoclusters (1.45 ± 0.05 nm), functioning as peroxidase-like nanozymes within a colorimetric assay tailored for rational HOSC estimation. This study validates both the characterization and remarkable stability of laminarin-Os. By leveraging the abundant surface negative charges of laminarin-Os and the surface hydroxyls of laminarin, oxidation reactions are facilitated, augmenting laminarin-Os's affinity for 3,3',5,5'-tetramethylbenzidine (TMB) (KM = 0.04 mM). This enables the laminarin-Os-based colorimetric assay to respond to ·OH more effectively than citrate-, albumin-, or other polysaccharides-based Os. In addition, experimental results also validate the selective peroxidase-like behavior of laminarin-Os under acidic conditions. Antioxidants like ascorbic acid, glutathione, tannic acid, and cysteine inhibit absorbance at 652 nm in the colorimetric platform using laminarin-Os's peroxidase-like activity. Compared with commercial kits, this assay demonstrates superior sensitivity (e.g., responds to ascorbic acid 0.01-0.075 mM, glutathione 1-15 µg/mL, tannic acid 0.5-5 µM, and monoammonium glycyrrhizinate cysteine 1.06-10.63 µM) and HOSC testing for glutathione, tannic acid, and monoammonium glycyrrhizinate cysteine. Overall, this study introduces a novel Os nanozyme with exceptional TMB affinity and ·OH selectivity, paving the way for HOSC estimation in biomedical research, pharmaceutical analysis, drug quality control, and beyond.

Intrauterine fetal death due to rupture of umbilical vessels: a rare case of furcate cord insertion.

Furcate cord insertion refers to the separation of umbilical vessels before reaching the placenta, where the branching vessels normally attach at the edge of the placental parenchyma or near the placental membranes. This is an extremely rare abnormal umbilical cord insertion. This paper reported a case of a furcate cord insertion, where the rupture of exposed umbilical vessels led to intrauterine fetal death at full term. Through literature review, we analyzed the prenatal ultrasound characteristics and pregnancy outcomes of furcate cord insertions, with the aim to improve detection rates and reduce the risk of adverse pregnancy outcomes.

Cold exposure-induced plasma exosomes impair bone mass by inhibiting autophagy.

Recently, environmental temperature has been shown to regulate bone homeostasis. However, the mechanisms by which cold exposure affects bone mass remain unclear. In our present study, we observed that exposure to cold temperature (CT) decreased bone mass and quality in mice. Furthermore, a transplant of exosomes derived from the plasma of mice exposed to cold temperature (CT-EXO) can also impair the osteogenic differentiation of BMSCs and decrease bone mass by inhibiting autophagic activity. Rapamycin, a potent inducer of autophagy, can reverse cold exposure or CT-EXO-induced bone loss. Microarray sequencing revealed that cold exposure increases the miR-25-3p level in CT-EXO. Mechanistic studies showed that miR-25-3p can inhibit the osteogenic differentiation and autophagic activity of BMSCs. It is shown that inhibition of exosomes release or downregulation of miR-25-3p level can suppress CT-induced bone loss. This study identifies that CT-EXO mediates CT-induced osteoporotic effects through miR-25-3p by inhibiting autophagy via targeting SATB2, presenting a novel mechanism underlying the effect of cold temperature on bone mass.

Identification of an Enterococcus faecium strain isolated from raw bovine milk co-harbouring the oxazolidinone resistance genes optrA and poxtA in China.

Oxazolidinones are potent antimicrobial agents used to treat human infections caused by multidrug-resistant Gram-positive bacteria. The growing resistance to oxazolidinones poses a significant threat to public health. In August 2021, a linezolid-resistant Enterococcus faecium BN83 was isolated from a raw milk sample of cow in Inner Mongolia, China. This isolate exhibited a multidrug resistance phenotype and was resistant to most of drugs tested including linezolid and tedizolid. PCR detection showed that two mobile oxazolidinones resistance genes, optrA and poxtA, were present in this isolate. Whole genome sequencing analysis revealed that the genes optrA and poxtA were located on two different plasmids, designated as pBN83-1 and pBN83-2, belonging to RepA_N and Inc18 families respectively. Genetic context analysis suggested that optrA gene on plasmid pBN83-1 was located in transposon Tn6261 initially found in E. faecalis. Comprehensive analysis revealed that Tn6261 act as an important horizontal transmission vector for the spread of optrA in E. faecium. Additionally, poxtA-bearing pBN83-2 displayed high similarity to numerous plasmids from Enterococcus of different origin and pBN83-2-like plasmid represented a key mobile genetic element involved in movement of poxtA in enterococcal species. The presence of optrA- and poxtA-carrying E. faecium in raw bovine milk represents a public health concern and active surveillance is urgently warranted to investigate the prevalence of oxazolidinone resistance genes in animal-derived food products.

Enhanced Iturin A Production of Engineered Bacillus amyloliquefaciens by Knockout of Endogenous Plasmid and Rap Phosphatase Genes.

Iturin A biosynthesis has garnered considerable interest, yet bottlenecks persist in its low productivity in wild strains and the ability to engineer Bacillus amyloliquefaciens producers. This study reveals that deleting the endogenous plasmid, plas1, from the wild-type B. amyloliquefaciens HM618 notably enhances iturin A synthesis, likely related to the effect of the Rap phosphatase gene within plas1. Furthermore, inactivating Rap phosphatase-related genes (rapC, rapF, and rapH) in the genome of the strain also improved the iturin A level and specific productivity while reducing cell growth. Strategic rap genes and plasmid elimination achieved a synergistic balance between cell growth and iturin A production. Engineered strain HM-DR13 exhibited an increase in iturin A level to 849.9 mg/L within 48 h, significantly shortening the production period. These insights underscore the critical roles of endogenous plasmids and Rap phosphatases in iturin A biosynthesis, presenting a novel engineering strategy to optimize iturin A production in B. amyloliquefaciens.

Platelet-derived major histocompatibility complex class I coating on Treponema pallidum attenuates natural killer cell lethality.

The evasive tactics of Treponema pallidum pose a major challenge in combating and eradicating syphilis. Natural killer (NK) cells mediate important effector functions in the control of pathogenic infection, preferentially eliminating targets with low or no expression of major histocompatibility complex (MHC) class I. To clarify T. pallidum's mechanisms in evading NK-mediated immunosurveillance, experiments were performed to explore the cross-talk relations among T. pallidum, NK cells, and platelets. T. pallidum adhered to, activated, and promoted particle secretion of platelets. After preincubation with T. pallidum, platelets expressed and secreted high levels of MHC class I, subsequently transferring them to the surface of T. pallidum, potentially inducing an immune phenotype characterized by the "pseudo-expression" of MHC class I on the surface of T. pallidum (hereafter referred to a "pseudo-expression" of MHC class I). The polA mRNA assay showed that platelet-preincubated T. pallidum group exhibited a significantly higher copy number of polA transcript than the T. pallidum group. The survival rate of T. pallidum mirrored that of polA mRNA, indicating that preincubation of T. pallidum with platelets attenuated NK cell lethality. Platelets pseudo-expressed the MHC class I ligand on the T. pallidum surface, facilitating binding to killer cell immunoglobulin-like receptors with two immunoglobulin domains and long cytoplasmic tail 3 (KIR2DL3) on NK cells and initiating dephosphorylation of Vav1 and phosphorylation of Crk, ultimately attenuating NK cell lethality. Our findings elucidate the mechanism by which platelets transfer MHC class I to the T. pallidum surface to evade NK cell immune clearance.

Vesicle-associated membrane protein 8 knockdown exerts anti-proliferative, pro-apoptotic, anti-autophagic, and pro-ferroptotic effects on colorectal cancer cells by inhibition of the JAK/STAT3 pathway.

Vesicle-associated membrane protein 8 (VAMP8), a soluble n-ethylmaleimide-sensitive factor receptor protein, acts as an oncogenic gene in the progression of several malignancies. Nevertheless, the roles and mechanisms of VAMP8 in colorectal cancer (CRC) progression remain unknown. The expression and prognostic significance of VAMP8 in CRC samples were analyzed through bioinformatics analyses. Cell proliferation was detected using CCK-8 and EdU incorporation assays and apoptosis was evaluated via flow cytometry. Western blot analysis was conducted to examine the protein expression. Ferroptosis was evaluated by measurement of iron metabolism, lipid peroxidation, and glutathione (GSH) content. VAMP8 was increased in CRC samples relative to normal samples on the basis of GEPIA and HPA databases. CRC patients with high level of VAMP8 had a worse overall survival. VAMP8 depletion led to a suppression of proliferation and promotion of apoptosis in CRC cells. Additionally, VAMP8 knockdown suppressed beclin1 expression and LC3-II/LC3-I ratio, elevated p62 expression, increased Fe2+, labile iron pool, lipid reactive oxygen species, and malondialdehyde levels, and repressed GSH content and glutathione peroxidase activity. Moreover, VAMP8 knockdown inhibited the activation of janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathway in CRC cells. Mechanistically, activation of the JAK/STAT3 pathway by JAK1 or JAK2 overexpression attenuated VAMP8 silencing-mediated anti-proliferative, pro-apoptotic, anti-autophagic, and pro-ferroptotic effects on CRC cells. In conclusion, VAMP8 knockdown affects the proliferation, apoptosis, autophagy, and ferroptosis by the JAK/STAT3 pathway in CRC cells.

A predictive model for patent ductus arteriosus seven days postpartum in preterm infants: an ultrasound-based assessment of ductus arteriosus intimal thickness within 24†h after birth.

Objectives: To develop a predictive model for patent ductus arteriosus (PDA) in preterm infants at seven days postpartum. The model employs ultrasound measurements of the ductus arteriosus (DA) intimal thickness (IT) obtained within 24 h after birth. Methods: One hundred and five preterm infants with gestational ages ranging from 27.0 to 36.7 weeks admitted within 24 h following birth were prospectively enrolled. Echocardiographic assessments were performed to measure DA IT within 24 h after birth, and DA status was evaluated through echocardiography on the seventh day postpartum. Potential predictors were considered, including traditional clinical risk factors, M-mode ultrasound parameters, lumen diameter of the DA (LD), and DA flow metrics. A final prediction model was formulated through bidirectional stepwise regression analysis and subsequently subjected to internal validation. The model's discriminative ability, calibration, and clinical applicability were also assessed. Results: The final predictive model included birth weight, application of mechanical ventilation, left ventricular end-diastolic diameter (LVEDd), LD, and the logarithm of IT (logIT). The receiver operating characteristic (ROC) curve for the model, predicated on logIT, exhibited excellent discriminative power with an area under the curve (AUC) of 0.985 (95% CI: 0.966-1.000), sensitivity of 1.000, and specificity of 0.909. Moreover, the model demonstrated robust calibration and goodness-of-fit (χ2 value = 0.560, p > 0.05), as well as strong reproducibility (accuracy: 0.935, Kappa: 0.773), as evidenced by 10-fold cross-validation. A decision curve analysis confirmed the model's broad clinical utility. Conclusions: Our study successfully establishes a predictive model for PDA in preterm infants at seven days postpartum, leveraging the measurement of DA IT. This model enables identifying, within the first 24 h of life, infants who are likely to benefit from timely DA closure, thereby informing treatment decisions.

Engineering Phage Nanocarriers Integrated with Bio-Intelligent Plasmids for Personalized and Tunable Enzyme Delivery to Enhance Chemodynamic Therapy.

Customizable and number-tunable enzyme delivery nanocarriers will be useful in tumor therapy. Herein, a phage vehicle, T4-Lox-DNA-Fe (TLDF), which adeptly modulates enzyme numbers using phage display technology to remodel the tumor microenvironment (TME) is presented. Regarding the demand for lactic acid in tumors, each phage is engineered to display 720 lactate oxidase (Lox), contributing to the depletion of lactic acid to restructure the tumor's energy metabolism. The phage vehicle incorporated dextran iron (Fe) with Fenton reaction capabilities. H2O2 is generated through the Lox catalytic reaction, amplifying the H2O2 supply for dextran iron-based chemodynamic therapy (CDT). Drawing inspiration from the erythropoietin (EPO) biosynthetic process, an EPO enhancer is constructed to impart the EPO-Keap1 plasmid (DNA) with tumor hypoxia-activated functionality, disrupting the redox homeostasis of the TME. Lox consumes local oxygen, and positive feedback between the Lox and the plasmid promotes the expression of kelch ECH Associated Protein 1 (Keap1). Consequently, the downregulation of the antioxidant transcription factor Nrf2, in synergy with CDT, amplifies the oxidative killing effect, leading to tumor suppression of up to 78%. This study seamlessly integrates adaptable T4 phage vehicles with bio-intelligent plasmids, presenting a promising approach for tumor therapy.

Comparison of six Z-score formulas based on echocardiography for coronary artery lesions in Kawasaki disease.

GOAL: Kawasaki disease (KD) patients are at risk of developing the serious complication of coronary artery dilation (CAD). To diagnose CAD caused by KD, various Z-Score formulas are used worldwide. This paper aims to evaluate the differences and inclusiveness among the six most commonly used Z-Score formulas in diagnosing CAD in Suzhou, China. Additionally, the study seeks to compare the differences in CAD diagnosis among different high-risk factor groups. By doing so, this research provides a valuable reference for accurately diagnosing CAD in KD patients. METHOD: This paper presents a retrospective analysis of 1509 patients diagnosed with KD at the Children's Hospital of Soochow University between January 2018 and December 2020. We collected the patients' clinical and echocardiographic data and used six Z-Score formulas (Kobayashi et al., de Zorzi et al., Kurotobi et al., McCrindle et al., Olivieri et al., and Dallaire et al.) to diagnose the degree of CAD in different segments. We then compared the diagnostic differences and inclusiveness of these formulas, especially the diagnostic differences in medium to giant CAA. To achieve this, we divided the patients into groups based on their age (≤12 months, 13-30 months, and > 30 months) and fever duration (≤5 days, 6-7 days, 8-9 days, and ≥ 10 days). Using the McNemar test and the Kappa test, we compared the differences and the consistencies of CDA diagnosis among the six Z-Score formulas. Moreover, we used the Friedman test and Chi-square segmentation formula to compare the differences in age and number of fever duration between groups and to compare each Z-Score formula pair within the group. RESULTS: Except for the LMCA segment, where there were no statistically significant differences between de Zorzi formula and McCrindle formula, the Z-score formulas showed statistically significant differences in the degree of CAD diagnosis across all other segments. Inclusiveness assessment revealed that Kobayashi formula and Dallaire formula showed significantly higher rates of dilatation (6.58% and 5.32%), or of small aneurysms (6.52% and 4.52%) compared to other formulas (1.0%-1.73%). Medium aneurysms were also more likely to be identified with Kobayashi and Dallaire formulas (0.8% and 0.8%) compared to the remaining formulas (0.13-0.40%). There are significant differences in the diagnoses of medium to giant CAA made by these six formulas in LAD and RCA. The longer the duration of fever and the younger the age, the higher the diagnosis rates of CAD and CAA. There were no statistically significant differences between de Zorzi formula and McCrindle formula, de Zorzi formula and Oliveri formula, and Kurotobi formula and Dallaire formula within the four groups based on the duration of fever. Similarly, there were no statistically significant differences between Kobayashi formula and Dallaire formula, and between de Zorzi formula and Oliveri formula in the age groups of ≤12 months and 13-30 months. CONCLUSION: There are diagnostic differences among these six Z-score formulas, considering the aforementioned statistics. Kobayashi formula and Dallaire formula are more inclusive, and less likely to under-diagnose significant CAD. They perform evenly for dilatation only, for small aneurysms and the median size aneurysms, and that is for segments of LMCA, LAD and RCA. In addition, McCrindle formula joins the "inclusive" pack for LAD and RCA in the matter of CAD. The younger the age of the patients and the longer the duration of fever, the higher the diagnosis rates of CAD and CAA. Furthermore, the younger the age of the patients and the shorter the duration of fever, the greater the differences between the various formulas.