Targeted gene sequencing and transcriptome sequencing reveal characteristics of NUP98 rearrangement in pediatric acute myeloid leukemia.

BACKGROUND: NUP98 rearrangements (NUP98-r) are rare but overrepresented mutations in pediatric acute myeloid leukemia (AML) patients. NUP98-r is often associated with chemotherapy resistance and a particularly poor prognosis. Therefore, characterizing pediatric AML with NUP98-r to identify aberrations is critically important. METHODS: Here, we retrospectively analyzed the clinicopathological features, genomic and transcriptomic landscapes, treatments, and outcomes of pediatric patients with AML. RESULTS: Nine patients with NUP98-r mutations were identified in our cohort of 142 patients. Ten mutated genes were detected in patients with NUP98-r. The frequency of FLT3-ITD mutations differed significantly between the groups harboring NUP98-r and those without NUP98-r (P = 0.035). Unsupervised hierarchical clustering via RNA sequencing data from 21 AML patients revealed that NUP98-r samples clustered together, strongly suggesting a distinct subtype. Compared with that in the non-NUP98-r fusion and no fusion groups, CMAHP expression was significantly upregulated in the NUP98-r samples (P < 0.001 and P = 0.001, respectively). Multivariate Cox regression analyses demonstrated that patients harboring NUP98-r (P < 0.001) and WT1 mutations (P = 0.030) had worse relapse-free survival, and patients harboring NUP98-r (P < 0.008) presented lower overall survival. CONCLUSIONS: These investigations contribute to the understanding of the molecular characteristics, risk stratification, and prognostic evaluation of pediatric AML patients.

Bio-based sunflower carbon/polyethylene glycol shape-stabilized phase change materials for thermal energy storage.

The exploitation of shape-stabilized phase change materials with high thermal conductivity and energy storage capacity is an effective strategy for improving energy efficiency. In this work, sunflower stem carbon/polyethylene glycol (SS-PEG) and sunflower receptacle carbon/polyethylene glycol (SR-PEG) shape-stabilized phase change materials, utilizing sunflower stem and receptacle biomass carbon with high specific surface area and pore volume obtained by carbonization as frameworks and polyethylene glycol as an energy storage material, were prepared by the vacuum impregnation method. The ability to load polyethylene glycol into the pore structure of carbon materials in different sunflower parts was mainly investigated, and the micro-morphology, compositional structure and thermal properties were characterized and analyzed using SEM, IR spectroscopy, XRD, DSC and TG techniques. The results showed that the carbonized sunflower stems maintained the sieve pore structure, and the carbonized sunflower receptacle was a macroporous structure containing a large number of three-dimensional interconnections. At the same time, the interaction between polyethylene glycol and each carbon material occurred through physisorption. The melting enthalpies of SS-PEG and SR-PEG shape-stabilized phase change materials were 153.4 J g-1 and 171.5 J g-1, respectively, and the loading rates reached 81.9% and 91.5%, with initial thermal decomposition temperatures (T 5%) of 344 °C and 368 °C.

Culture positivity and distribution of the conjunctival sac bacteria in the perioperative period of corneal refractive surgery.

The objective of this study was to investigate the culture positivity and distribution of the conjunctival sac bacteria in the perioperative period of corneal refractive surgery. The selected time points of the perioperative period included before the use of antibiotic eye drops, before eye wash (after the use of antibiotic eye drops), after eye wash, and immediately after surgery. Conjunctival specimens obtained at the four time points were cultured to detect the positivity and distribution of bacteria. Before prophylactic antibiotic eye drops were administered, 49 eyes (50%) had positive bacterial culture results, with 45 isolates (91.8%) identified as Staphylococcus epidermidis. The culture positivity rates of the conjunctival sac specimens before eye wash, after eye wash, and immediately after surgery were 19.4%, 3.1%, and 4.1%, respectively. The difference was significant before and after the use of antibiotics and before and after eye wash (both P < 0.001). Staphylococcus epidermidis was the major pathogen in the conjunctival sac before corneal refractive surgery, and the culture positivity rate of the conjunctival bacteria was higher in males. Sixteen of 37 eyes (43.2%) with contact lenses had positive culture results, compared to 33 of 61 eyes (54.1%) without contact lenses (P > 0.05). The judicious preoperative use of antibiotic eye drops combined with the surgical sterile eye wash procedure maximised the removal of conjunctival sac bacteria. Skilled surgical manipulations generally did not increase the risk of infection.

An engineered cellular carrier delivers miR-138-5p to enhance mitophagy and protect hypoxic-injured neurons via the DNMT3A/Rhebl1 axis.

Mitophagy influences the progression and prognosis of ischemic stroke (IS). However, whether DNA methylation in the brain is associated with altered mitophagy in hypoxia-injured neurons remains unclear. Here, miR-138-5p was found to be highly expressed in exosomes secreted by astrocytes stimulated with oxygen and glucose deprivation/re-oxygenation (OGD/R), which could influence the recovery of OGD/R-injured neurons through autophagy. Mechanistically, miR-138-5p promotes the stable expression of Ras homolog enriched in brain like 1(Rhebl1) through DNA-methyltransferase-3a (DNMT3A), thereby enhancing ubiquitin-dependent mitophagy to maintain mitochondrial homeostasis. Furthermore, we employed glycosylation engineering and bioorthogonal click reactions to load mirna onto the surface of microglia and deliver them to injured region utilising the inflammatory chemotactic properties of microglia to achieve drug-targeted delivery to the central nervous system (CNS). Our findings demonstrate miR-138-5p improves mitochondrial function in neurons through the miR-138-5p/DNMT3A/Rhebl1 axis. Additionally, our engineered cell vector-targeted delivery system could be promising for treating IS. STATEMENT OF SIGNIFICANCE: In this study, we demonstrated that miR-138-5p in exosomes secreted by astrocytes under hypoxia plays a critical role in the treatment of hypoxia-injured neurons. And we find a new target of miR-138-5p, DNMT3A, which affects neuronal mitophagy and thus exerts a protective effect by regulating the methylation of Rbebl1. Furthermore, we have developed a carrier delivery system by combining miR-138-5p with the cell membrane of microglia and utilized the inflammatory chemotactic properties of microglia to deliver this system to the brain via intravenous injection. This groundbreaking study not only provides a novel therapeutic approach for ischemia-reperfusion treatment but also establishes a solid theoretical foundation for further research on targeted drug delivery for central nervous system diseases with promising clinical applications.

BCAA-producing Clostridium symbiosum promotes colorectal tumorigenesis through the modulation of host cholesterol metabolism.

Identification of potential bacterial players in colorectal tumorigenesis has been a focus of intense research. Herein, we find that Clostridium symbiosum (C. symbiosum) is selectively enriched in tumor tissues of patients with colorectal cancer (CRC) and associated with higher colorectal adenoma recurrence after endoscopic polypectomy. The tumorigenic effect of C. symbiosum is observed in multiple murine models. Single-cell transcriptome profiling along with functional assays demonstrates that C. symbiosum promotes the proliferation of colonic stem cells and enhances cancer stemness. Mechanistically, C. symbiosum intensifies cellular cholesterol synthesis by producing branched-chain amino acids (BCAAs), which sequentially activates Sonic hedgehog signaling. Low dietary BCAA intake or blockade of cholesterol synthesis by statins could partially abrogate the C. symbiosum-induced cell proliferation in vivo and in vitro. Collectively, we reveal C. symbiosum as a bacterial driver of colorectal tumorigenesis, thus identifying a potential target in CRC prediction, prevention, and treatment.

Comparison analysis of the burden and attributable risk factors of early-onset and late-onset colorectal cancer in China from 1990 to 2019.

OBJECTIVES: The project intended to analyze the impact of burden and related risk factors of late-onset colorectal cancer (LOCRC) and early-onset colorectal cancer (EOCRC) in China, thus offering essential references for optimizing prevention and control strategies. METHOD: Global Burden of Disease Study was employed to describe burden changes of EOCRC and LOCRC in China during 1990-2019, containing the numbers of incidence, deaths, prevalence, and disability-adjusted life years (DALYs), and to compare attributable deaths and DALYs risk factors in varying age and sex segments. RESULTS: The numbers and corresponding crude rates of incidence, deaths, prevalence, and DALYs of EOCRC and LOCRC in China during 1990-2019 demonstrated an upward trend across all age categories, with males being dramatically predominant. Overall, over time, the impact of a low-calcium diet and a low-fiber diet on mortality and DALY rates decreased, while the impact of other risk factors increased. In terms of gender, the risk factors affecting males changed greatly, with smoking, inadequate milk intake, and the low whole-grain diet being the main factors in 2019, while in 1990, the main factors were the low-calcium diet, smoking, and inadequate milk intake. CONCLUSION: The burden of colorectal cancer in China is concerning. Patients grouped by diagnostic age exhibit different characteristics, indicating the need for high-quality research in the future to achieve personalized medicine tailored to different population characteristics.

Fully automated hybrid approach on conventional MRI for triaging clinically significant liver fibrosis: A multi-center cohort study.

Establishing reliable noninvasive tools to precisely diagnose clinically significant liver fibrosis (SF, ≥F2) remains an unmet need. We aimed to build a combined radiomics-clinic (CoRC) model for triaging SF and explore the additive value of the CoRC model to transient elastography-based liver stiffness measurement (FibroScan, TE-LSM). This retrospective study recruited 595 patients with biopsy-proven liver fibrosis at two centers between January 2015 and December 2021. At Center 1, the patients before December 2018 were randomly split into training (276) and internal test (118) sets, the remaining were time-independent as a temporal test set (96). Another data set (105) from Center 2 was collected for external testing. Radiomics scores were built with selected features from Deep learning-based (ResUNet) automated whole liver segmentations on MRI (T2FS and delayed enhanced-T1WI). The CoRC model incorporated radiomics scores and relevant clinical variables with logistic regression, comparing routine approaches. Diagnostic performance was evaluated by the area under the receiver operating characteristic curve (AUC). The additive value of the CoRC model to TE-LSM was investigated, considering necroinflammation. The CoRC model achieved AUCs of 0.79 (0.70, 0.86), 0.82 (0.73, 0.89), and 0.81 (0.72-0.91), outperformed FIB-4, APRI (all p < 0.05) in the internal, temporal, and external test sets and maintained the discriminatory power in G0-1 subgroups (AUCs range, 0.85-0.86; all p < 0.05). The AUCs of joint CoRC-LSM model were 0.86 (0.79-0.94), and 0.81 (0.72-0.90) in the internal and temporal sets (p = 0.01). The CoRC model was useful for triaging SF, and may add value to TE-LSM.

Gut microbiota contributes to high-altitude hypoxia acclimatization of human populations.

BACKGROUND: The relationship between human gut microbiota and high-altitude hypoxia acclimatization remains highly controversial. This stems primarily from uncertainties regarding both the potential temporal changes in the microbiota under such conditions and the existence of any dominant or core bacteria that may assist in host acclimatization. RESULTS: To address these issues, and to control for variables commonly present in previous studies which significantly impact the results obtained, namely genetic background, ethnicity, lifestyle, and diet, we conducted a 108-day longitudinal study on the same cohort comprising 45 healthy Han adults who traveled from lowland Chongqing, 243 masl, to high-altitude plateau Lhasa, Xizang, 3658 masl, and back. Using shotgun metagenomic profiling, we study temporal changes in gut microbiota composition at different timepoints. The results show a significant reduction in the species and functional diversity of the gut microbiota, along with a marked increase in functional redundancy. These changes are primarily driven by the overgrowth of Blautia A, a genus that is also abundant in six independent Han cohorts with long-term duration in lower hypoxia environment in Shigatse, Xizang, at 4700 masl. Further animal experiments indicate that Blautia A-fed mice exhibit enhanced intestinal health and a better acclimatization phenotype to sustained hypoxic stress. CONCLUSIONS: Our study underscores the importance of Blautia A species in the gut microbiota's rapid response to high-altitude hypoxia and its potential role in maintaining intestinal health and aiding host adaptation to extreme environments, likely via anti-inflammation and intestinal barrier protection.

Microsporidian EnP1 alters host cell H2B monoubiquitination and prevents ferroptosis facilitating microsporidia survival.

Microsporidia are intracellular eukaryotic pathogens that pose a substantial threat to immunocompromised hosts. The way these pathogens manipulate host cells during infection remains poorly understood. Using a proximity biotinylation strategy we established that microsporidian EnP1 is a nucleus-targeted effector that modifies the host cell environment. EnP1's translocation to the host nucleus is meditated by nuclear localization signals (NLSs). In the nucleus, EnP1 interacts with host histone H2B. This interaction disrupts H2B monoubiquitination (H2Bub), subsequently impacting p53 expression. Crucially, this inhibition of p53 weakens its control over the downstream target gene SLC7A11, enhancing the host cell's resilience against ferroptosis during microsporidian infection. This favorable condition promotes the proliferation of microsporidia within the host cell. These findings shed light on the molecular mechanisms by which microsporidia modify their host cells to facilitate their survival.

Accelerated healing of intractable biofilm-infected diabetic wounds by trypsin-loaded quaternized chitosan hydrogels that disrupt extracellular polymeric substances and eradicate bacteria.

Complex and stubborn bacterial biofilm infections significantly hinder diabetic wound healing and threaten public health. Therefore, a dressing material that effectively clears biofilms and promotes wound healing is urgently required. Herein, we introduce a novel strategy for simultaneously dispersing extracellular polymeric substances and eradicating drug-resistant bacteria. We prepared an ultrabroad-spectrum and injectable quaternized chitosan (QCS) hydrogel loaded with trypsin, which degrades biofilm extracellular proteins. Increased temperature initiated QCS gelation to form the hydrogel, enabling the sustained release of trypsin and effective adherence of the hydrogel to irregularly shaped wounds. To reproduce clinical scenarios, biofilms formed by a mixture of Staphylococcus aureus (S. aureus), Methicillin-resistant S. aureus, and Pseudomonas aeruginosa were administered to the wounds of rats with streptozotocin-induced diabetes. Under these severe infection conditions, the hydrogel efficiently suppressed inflammation, promoted angiogenesis, and enhanced collagen deposition, resulting in accelerated healing of diabetic wounds. Notably, the hydrogel demonstrates excellent biocompatibility without cytotoxicity. In summary, we present a trypsin-loaded QCS hydrogel with tremendous clinical applications potential for the treatment of chronic infected wounds.

Trametinib boosts palbociclib's efficacy in breast cancer via autophagy inhibition.

Breast cancer, a predominant global health issue, requires ongoing exploration of new therapeutic strategies. Palbociclib (PAL), a well-known cyclin-dependent kinase (CDK) inhibitor, plays a critical role in breast cancer treatment. While its efficacy is recognized, the interplay between PAL and cellular autophagy, particularly in the context of the RAF/MEK/ERK signaling pathway, remains insufficiently explored. This study investigates PAL's inhibitory effects on breast cancer using both in vitro (MCF7 and MDA-MB-468 cells) and in vivo (tumor-bearing nude mice) models. Aimed at elucidating the impact of PAL on autophagic processes and exploring the potential of combining it with trametinib (TRA), an MEK inhibitor, our research seeks to address the challenge of PAL-induced drug resistance. Our findings reveal that PAL significantly decreases the viability of MCF7 and MDA-MB-468 cells and reduces tumor size in mice while showing minimal cytotoxicity in MCF10A cells. However, PAL also induces protective autophagy, potentially leading to drug resistance via the RAF/MEK/ERK pathway activation. Introducing TRA effectively neutralized this autophagy, enhancing PAL's anti-tumor efficacy. A combination of PAL and TRA synergistically reduced cell viability and proliferation, and in vivo studies showed notable tumor size reduction. In conclusion, the PAL and TRA combination emerges as a promising strategy for overcoming PAL-induced resistance, offering a new horizon in breast cancer treatment.

A composite PET-matrix patch enhances tendon regeneration and tendon-to-bone integration for bridging repair of the chronic massive rotator cuff tears in a rabbit model.

In recent years, bridging repair has emerged as an effective approach for the treatment of massive rotator cuff tears (MRCTs). The objective of this study was to develop a composite patch that combines superior mechanical strength and biocompatibility and evaluate its potential for enhancing the outcomes of bridging repair for MRCTs. The composite patch, referred to as the PET-matrix patch (PM), was fabricated by immersing a plain-woven PET patch in decellularized matrix gel and utilizing the freeze-drying technique. The results demonstrated that the PM has reliable mechanical properties, with a maximum failure load of up to 480 N. The decellularized matrix sponge (DMS), present on the surface of the PM, displayed a loose and porous structure, with an average pore size of 62.51 µm and a porosity of 95.43%. In vitro experiments showed significant elongation of tenocytes on the DMS, with cells spanning across multiple pores and extending multiple protrusions as observed on SEM images. In contrast, tenocytes on the PET patch appeared smaller in size and lacked significant elongation. Additionally, the DMS facilitated the proliferation, migration and differentiation of tenocytes. In a rabbit model of chronic MRCTs, the PM group showed superior outcomes compared to the PET group at 4, 8 and 12 weeks after bridging repair. The PM group displayed significantly higher tendon maturing score, larger collagen diameter in the regenerated tendon and improved tendon-to-bone healing scores compared to the PET group (P < 0.05). Moreover, the maximum failure load of the tendon-bone complex in the PM group was significantly higher than that in the PET group (P < 0.05). In summary, the PM possesses reliable mechanical properties and excellent cytocompatibility, which can significantly improve the outcomes of bridging repair for chronic MRCTs in rabbits. Therefore, it holds great potential for clinical applications.

Silencing Exosomal circ102927 Inhibits Foot Melanoma Metastasis via Regulating Invasiveness, Epithelial-Mesenchymal Transition and Apoptosis.

Background: Exosomes contain abundant circular RNAs (circRNAs), playing an important role in intercellular communication. However, the function and underlying molecular mechanism of exosomal circRNAs in foot metastatic melanoma remain unclear. Methods: Twelve differentially expressed exosomal circRNAs between patients with metastatic and primary foot melanoma were screened through high-throughput sequencing, and their expression levels were detected by the real-time reverse transcriptase-polymerase chain reaction (RT-qPCR). CircRNA102927 silencing and overexpression A2058 cell line was constructed, and the effects of circRNA102927 on cell proliferation, apoptosis, migration, invasion, and epithelial-mesenchymal transition (EMT) were assessed using cell counting kit-8 (CCK-8), flow cytometry, wound healing, Transwell, and Western blot assays, respectively. Results: Twelve differentially expressed exosomal circRNAs were screened and ROC curve showed that six circRNAs could be used as the diagnostic biomarkers for metastatic melanoma. Melanoma-secreted exosomes induced the differentiation of CD4+ T cells into Treg cells. CircRNA102927 was highly expressed in metastatic melanomas. Functionally, circRNA102927 silencing inhibited proliferation, EMT, migration, and invasion in metastatic melanoma cells, while promoting apoptosis. Meanwhile, overexpression of circRNA102927 had the opposite effects. Conclusion: Our investigation suggests that silencing exosomal circRNA102927 may suppress foot melanoma metastasis by inhibiting invasiveness, EMT and promoting apoptosis.

Interspinous Motion Measurement Could Serve as a Quantitative Method for Assessing Bony Fusion after Anterior Cervical Corpectomy and Fusion (ACCF).

STUDY DESIGN: A retrospective diagnostic test study. OBJECTIVE: To establish quantitative fusion criteria for ACCF. SUMMARY OF BACKGROUND DATA: Currently, the criteria of fusion after ACCF remains controversial. Evaluation techniques such as observation of continuous bony trabeculae across the fusion site, were qualitative and conducted by naked eyes, limiting its accuracy. Dynamic fusion indicators such as interspinous motion (ISM), have been successfully utilized in anterior cervical discectomy and fusion (ACDF) for evaluating fusion and detecting pseudarthrosis. However, the accuracy of ISM in ACCF is unclear. METHODS: Patients underwent ACCF in our hospital were reviewed. Imaging data including dynamic radiographs and computed tomography (CT) scans were collected. The distance and angle form of ISM (ISM-dis and ISM-ang) were measured on dynamic radiograph, with CT as the gold standard for fusion. The correlation between ISM methods was analyzed using Spearmann correlation. Receiver Operating Characteristic (ROC) curves were used to evaluate the accuracy and generate optimal cut-off values. Three observers independently measured the data twice to determine interobserver and intraobserver reliability. RESULTS: Our study included 178 imaging datasets. ISM-dis showed positive correlation with ISM-ang (r=0.914). The area under ROC (AUC) for ISM-dis and ISM-ang was 0.926 and 0.893. Applying a cutoff value of 1.50 mm to ISM-dis yielded a sensitivity of 87.8% and specificity of 92.3% for detecting pseudarthrosis. For ISM-ang, a cutoff value of 1.75° resulted in a sensitivity of 79.1% and specificity of 92.3%. Intraobserver reliabilities for ISM-dis (0.986, 0.984 and 0.972) were higher than for ISM-ang (0.935, 0.963 and 0.935), as was interobserver reliability (0.985 for ISM-dis and 0.956 for ISM-ang). Fusion rates calculated using ISM-dis and ISM-ang were 52.4% and 61.9%. CONCLUSION: ISM can serve as an alternative to CT for assessing fusion, with ISM-dis at a 1.50 mm cutoff and ISM-ang at 1.75° demonstrating high diagnostic accuracy.

Host cell manipulation by microsporidia secreted effectors: Insights into intracellular pathogenesis.

Microsporidia are prolific producers of effector molecules, encompassing both proteins and nonproteinaceous effectors, such as toxins, small RNAs, and small peptides. These secreted effectors play a pivotal role in the pathogenicity of microsporidia, enabling them to subvert the host's innate immunity and co-opt metabolic pathways to fuel their own growth and proliferation. However, the genomes of microsporidia, despite falling within the size range of bacteria, exhibit significant reductions in both structural and physiological features, thereby affecting the repertoire of secretory effectors to varying extents. This review focuses on recent advances in understanding how microsporidia modulate host cells through the secretion of effectors, highlighting current challenges and proposed solutions in deciphering the complexities of microsporidial secretory effectors.

The use of peripheral CD3+γδ+Vδ2+ T lymphocyte cells in combination with the ALBI score to predict immunotherapy response in patients with advanced hepatocellular carcinoma: a retrospective study.

BACKGROUND: Currently, there is a lack of effective indicators for predicting the efficacy of immunotherapy in patients with advanced hepatocellular carcinoma (HCC). This study aimed to investigate the expression and prognostic value of peripheral T lymphocyte subsets in advanced HCC. METHODS: Patients with advanced HCC who were treated with immune checkpoint inhibitors (ICIs) from December 2021 to December 2023 were included in the study. Flow cytometry was used to detect lymphocyte subsets before treatment. The patients were divided into disease control (DC) and nondisease control (nDC) groups based on treatment efficacy. Relationships between the clinical characteristics/peripheral T lymphocytes and immunotherapy efficacy were analyzed. The effectiveness of peripheral T lymphocyte subsets in predicting immunotherapy efficacy for patients with advanced HCC was analyzed using receiver operating characteristic (ROC) curves. RESULTS: A total of 40 eligible patients were included in this study. Non-DC was significantly associated with higher albumin-bilirubin (ALBI) scores. The percentages of γδ+Vδ2+PD1+ T cells and γδ+Vδ2+Tim3+ T cells were greater in the nDC group than in the DC group. Multivariable regression analysis revealed that the ALBI score and T lymphocytes expressing γδ+Vδ2+PD1+ and γδ+Vδ2+Tim3+ were founded to be independent influencing factors. The area under the ROC curve (AUC) values for these combinations was 0.944 (95% CI, 0.882 ~ 1.000). CONCLUSIONS: The calculation of the ALBI score and determination of the percentages CD3+γδ+Vδ2+PD1+ T lymphocytes and CD3+γδ+Vδ2+Tim3+ T lymphocytes in the peripheral blood of patients with advanced HCC are helpful for predicting the patients' responses to ICIs, helping to screen patients who may clinically benefit from immunotherapy. RETROSPECTIVELY REGISTERED: number: ChiCTR2400080409, date of registration: 2024-01-29.

Chemotactic recruitment of genetically engineered cell membrane-camouflaged metal-organic framework nanoparticles for ischemic osteonecrosis treatment.

Ischemic osteonecrosis, particularly glucocorticoid-induced osteonecrosis of the femoral head (GIONFH), is primarily due to the dysfunction of osteogenesis and angiogenesis. miRNA, as a therapeutic system with immense potential, plays a vital role in the treatment of various diseases. However, due to the unique microenvironmental structure of bone tissue, especially in the case of GIONFH, where there is a deficiency in the vascular system, it is challenging to effectively target and deliver to the ischemic osteonecrosis area. A drug delivery system assisted by genetically engineered cell membranes holds promise in addressing the challenge of targeted miRNA delivery. Herein, we leverage the potential of miR-21 in modulating osteogenesis and angiogenesis to design an innovative biomimetic nanoplatform system. First, we employed metal-organic frameworks (MOFs) as the core structure to load miR-21-m (miR-21-m@MOF). The nanoparticles were further coated with the membrane of bone marrow mesenchymal stem cells overexpressing CXCR4 (CM-miR-21-m@MOF), enhancing their ability to target ischemic bone areas via the CXCR4-SDF1 axis. These biomimetic nanocomposites possess both bone-targeting and ischemia-guiding capabilities, actively targeting GIONFH lesions to release miR-21-m into target cells, thereby silencing PTEN gene and activating the PI3K-AKT signaling pathway to regulate osteogenesis and angiogenesis. This innovative miRNA delivery system provides a promising therapeutic avenue for GIONFH and potentially other related ischemic bone diseases. STATEMENT OF SIGNIFICANCE.

Comparison of Caries and Gingival Status in Patients with Type 2 Diabetes and Healthy Children.

Background: Oral health problems often occur in patients with type 2 diabetes (T2D), and the incidences of dental caries and gingivitis increase as blood glucose (BG) levels rise. This work compared caries and gingival status of patients with T2D and healthy children to improve the understanding and attention of patients with T2D to oral health. Methods: Clinical data of 60 patients with T2D under the age of 10 from May 2020 to September 2022 were retrospectively collected and assigned to the diabetes group. Those 60 healthy children with the same physical examination were collected and assigned to the healthy group. Children in both groups underwent periodontal examination, dental caries examination, and gingival index examination. The prevalence, decayed, missed, and filled teeth (DMFT), caries average (CA), plaque index (PI), gingival crevicular bleeding index (GCBI), attachment loss (AL), and tooth looseness (TL) were observed and compared. Results: The prevalence of dental plaque (DP) (91.67%) and moderate to severe DP (45%) in the diabetes group was much higher based on those in the healthy group (73.33% and 23.33%) [1.25, 95% CI (0.96, 1.63), P < .001]. The prevalence of caries and CA was greatly higher in the diabetes group (75% vs. 21.67%, 2.88 vs. 1.06), and the incidence of gingivitis was higher (63.33% vs. 16.67%) [1.93, 95% CI (1.38, 2.70), P < .001]. Meanwhile, the diabetes group exhibited much higher PI (2.31 ± 0.13), GCBI (2.45 ± 0.28), AL (5.62 ± 0.47 mm), and TL (0.85 ± 0.17 mm) and exhibited obvious difference to those in the healthy group (0.92 ± 0.21, 0.86 ± 0.23, 1.65 ± 0.46mm, 0.36 ± 0.08 mm) [3.46, 95% CI (2.33, 5.15), P < .001]. Conclusion: The prevalence of dental caries and gingivitis in patients with T2D was higher than those in healthy children. Based on these findings, it is suggested that patients with T2D should be educated and encouraged to prioritize their oral health. Regular dental check-ups, proper oral hygiene practices, and preventive measures, such as professional cleanings and fluoride treatments, should be emphasized. Maintaining optimal blood glucose control is also crucial, as it may help reduce the risk and severity of oral health complications associated with diabetes.

Elevating Black fathers' experiences in the National Fatherhood Initiative: Strengths and areas for improvement of 24/7 Dad® curriculum and case management services.

The Healthy Marriage and Responsible Fatherhood grant program is one of the most robust mechanisms supporting fatherhood programming in the United States, with the gold standard of care including fatherhood curriculum (e.g., 24/7 Dad®) and case management services. Despite the fact that fatherhood in the United States is not a monolith and Black fathers make up over 40% of those served through Responsible Fatherhood (RF) program, little research explicitly centers the lived experiences of low-income Black fathers. The current study used focus groups with fathers (n = 23) and staff (n = 8) enrolled in a RF grantee program. Thematic analysis was used to determine programmatic mechanisms supporting these fathers' success and areas for improvement. Our findings highlight that the creation of a "safe space" by facilitators and the power of the group dynamic were essential elements for fathers' success overall. We also identified numerous programmatic mechanisms supporting Black fathers' success specific to fathering, healthy relationships, and economic stability. Finally, we highlighted important limitations that may impede the success of low-income, Black fathers related to the 24/7 Dad® curriculum, engagement efforts, and economic stability, and discuss related practice, policy, and research recommendations.