Effect fraction of Bletilla striata (Thunb.) Reichb.f. alleviates LPS-induced acute lung injury by inhibiting p47phox/NOX2 and promoting the Nrf2/HO-1 signaling pathway.

BACKGROUND & AIMS: The effect fraction of Bletilla striata (Thunb.) Reichb.f. (EFBS), a phenolic-rich extract, has significant protective effects on lipopolysaccharide (LPS)-induced acute lung injury (ALI), but its composition and molecular mechanisms are unclear. This study elucidated its chemical composition and possible protective mechanisms against LPS-induced ALI from an antioxidant perspective. METHODS: EFBS was prepared by ethanol extraction, enriched by polyamide column chromatography, and characterized using ultra-performance liquid chromatography/time-of-flight mass spectrometry. The LPS-induced ALI model and the RAW264.7 model were used to evaluate the regulatory effects of EFBS on oxidative stress, and transcriptome analysis was performed to explore its possible molecular mechanism. Then, the pathway by which EFBS regulates oxidative stress was validated through inhibitor intervention, flow cytometry, quantitative PCR, western blotting, and immunofluorescence techniques. RESULTS: A total of 22 compounds in EFBS were identified. The transcriptome analyses of RAW264.7 cells indicated that EFBS might reduce reactive oxygen species (ROS) production by inhibiting the p47phox/NADPH oxidase 2 (NOX2) pathway and upregulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. Both in vitro and in vivo data confirmed that EFBS significantly inhibited the expression and phosphorylation of p47phox protein, thereby weakening the p47phox/NOX2 pathway and reducing ROS production. EFBS significantly increased the expression of Nrf2 in primary peritoneal macrophages and lung tissue and promoted its nuclear translocation, dose-dependent increase in HO-1 levels, and enhancement of antioxidant activity. In vitro, both Nrf2 and HO-1 inhibitors significantly reduced the scavenging effects of EFBS on ROS, further confirming that EFBS exerts antioxidant effects at least partially by upregulating the Nrf2/HO-1 pathway. CONCLUSIONS: EFBS contains abundant phenanthrenes and dibenzyl polyphenols, which can reduce ROS production by inhibiting the p47phox/NOX2 pathway and enhance ROS clearance activity by upregulating the Nrf2/HO-1 pathway, thereby exerting regulatory effects on oxidative stress and improving LPS-induced ALI.

Progress in the treatment of drug-loaded nanomaterials in renal cell carcinoma.

Renal cell carcinoma (RCC) is a common urinary tract tumor that arises from the highly heterogeneous epithelium of the renal tubules. The incidence of kidney cancer is second only to the incidence of bladder cancer, and has shown an upward trend over time. Although surgery is the preferred treatment for localized RCC, treatment decisions should be customized to individual patients considering their overall health status and the risk of developing or worsening chronic kidney disease postoperatively. Anticancer drugs are preferred to prevent perioperative and long-term postoperative complications; however, resistance to chemotherapy remains a considerable problem during the treatment process. To overcome this challenge, nanocarriers have emerged as a promising strategy for targeted drug delivery for cancer treatment. Nanocarriers can transport anticancer agents, achieving several-fold higher cytotoxic concentrations in tumors and minimizing toxicity to the remaining parts of the body. This article reviews the use of nanomaterials, such as liposomes, polymeric nanoparticles, nanocomposites, carbon nanomaterials, nanobubbles, nanomicelles, and mesoporous silica nanoparticles, for RCC treatment, and discusses their advantages and disadvantages.

Macrocyclization via remote meta-selective C-H olefination using a practical indolyl template.

The synthesis of macrocyclic compounds with different sizes and linkages remains a great challenge via transition metal-catalysed intramolecular C-H activation. Herein, we disclose an efficient macrocyclization strategy via Pd-catalysed remote meta-C-H olefination using a practical indolyl template. This approach was successfully employed to access macrolides and coumarins. In addition, the intermolecular meta-C-H olefination also worked well and was exemplified by the synthesis of antitumor drug belinostat from inexpensive and readily available benzenesulfonyl chloride. Notably, catalytic copper acetate and molecular oxygen were used in place of silver salts as oxidants. Furthermore, for the first time, the formation of a macrocyclophane cyclopalladated intermediate was detected through in situ Fourier-transform infrared monitoring experiments and ESI-MS.

Baicalin suppress the development of polycystic ovary syndrome via regulating the miR-874-3p/FOXO3 and miR-144/FOXO1 axis.

CONTEXT: Polycystic ovary syndrome (PCOS) is a common and complex disease caused by endocrine and metabolic dysfunction in women of reproductive age. Baicalin is reported to ameliorate PCOS. OBJECTIVE: This study determines whether baicalin could affect the progression of PCOS. MATERIALS AND METHODS: To establish an animal model of PCOS, female Sprague-Dawley (SD) rats were subcutaneously injected with dehydroepiandrosterone (DHEA, 60 mg/kg) for 20 days. Next, normal and PCOS mice were divided into 3 groups: control, PCOS, PCOS + Baicalin (20 mg/kg) groups. In addition, the levels of microRNA-874-3p (miR-874-3p) and microRNA-144 (miR-144) in ovarian tissues were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). RESULTS: Compared to the PCOS group, baicalin treatment significantly declined free testosterone (33.71 pg/mL vs. 56.05 pg/mL) and luteinizing hormone (LH; 3971.73 pg/mL vs. 5201.50 pg/mL) levels in rats with PCOS. Additionally, compared to the control group, 100 µM baicalin lessened miR-874-3p and miR-144 levels in human ovarian granulosa cells (KGN cells) by 36.87% and 32.57%, respectively. Furthermore, forkhead box O (FOXO) proteins FOXO1 and FOXO3 are the direct targets of miR-144 and miR-874-3p, respectively. Meanwhile, baicalin induced G0-G1 phase arrest (69.56 ± 3.7% at baicalin with 100 µM vs. 51.24 ± 3.2%, control) in KGN cells correlating with decreased p27 Kip1 (FOXO proteins downstream effector gene) expression by 55.5%; however, miR-874-3p or miR-144 overexpression could abolish this effect. CONCLUSIONS: Baicalin could alleviate the symptoms of PCOS via regulating miR-874-3p/FOXO3 and miR-144/FOXO1 axis, demonstrating its potential utility in PCOS treatment.

DNA replication initiation factor RECQ4 possesses a role in antagonizing DNA replication initiation.

Deletion of the conserved C-terminus of the Rothmund-Thomson syndrome helicase RECQ4 is highly tumorigenic. However, while the RECQ4 N-terminus is known to facilitate DNA replication initiation, the function of its C-terminus remains unclear. Using an unbiased proteomic approach, we identify an interaction between the RECQ4 N-terminus and the anaphase-promoting complex/cyclosome (APC/C) on human chromatin. We further show that this interaction stabilizes APC/C co-activator CDH1 and enhances APC/C-dependent degradation of the replication inhibitor Geminin, allowing replication factors to accumulate on chromatin. In contrast, the function is blocked by the RECQ4 C-terminus, which binds to protein inhibitors of APC/C. A cancer-prone, C-terminal-deleted RECQ4 mutation increases origin firing frequency, accelerates G1/S transition, and supports abnormally high DNA content. Our study reveals a role of the human RECQ4 C-terminus in antagonizing its N-terminus, thereby suppressing replication initiation, and this suppression is impaired by oncogenic mutations.

Nanoparticle-mediated therapeutic management in cholangiocarcinoma drug targeting: Current progress and future prospects.

Patients with cholangiocarcinoma (CCA) often have an unfavorable prognosis because of its insidious nature, low resectability rate, and poor response to anticancer drugs and radiotherapy, which makes early detection and treatment difficult. At present, CCA has a five-year overall survival rate (OS) of only 5%, despite advances in therapies. New an increasing number of evidence suggests that nanoplatforms may play a crucial role in enhancing the pharmacological effects and in reducing both short- and long-term side effects of cancer treatment. This document reviews the advantages and shortcomings of nanoparticles such as liposomes, polymeric nanoparticle，inorganic nanoparticle, nano-metals and nano-alloys, carbon dots, nano-micelles, dendrimer, nano-capsule, bio-Nanomaterials in the diagnosis and treatment of CCA and discuss the current challenges in of nanoplatforms for CCA.

Rituximab with high-dose methotrexate is effective and cost-effective in newly diagnosed primary central nervous system lymphoma.

Induction chemotherapy based on high-dose methotrexate is considered as the standard approach for newly diagnosed primary central nervous system lymphomas (PCNSLs). However, the best combination chemotherapeutic regimen remains unclear. This study aimed to determine the efficacy and toxicities of rituximab with methotrexate (R-M regimen). Consecutive 37 Chinese patients receiving R-M regimen as induction chemotherapy were retrospectively identified from January 2015 to June 2020 from our center in eastern China. Fourteen patients receiving rituximab plus methotrexate with cytarabine (R-MA regimen) at the same period were identified as the positive control group. The response rates, survival, toxicities, length of hospital stay (LOS), and cost were compared. Compared with the R-MA regimen, the R-M regimen showed comparable response rate and survival outcomes, but had fewer grade 3-4 hematological toxicities, shorter LOS, lower mean total hospitalization cost and lower mean total antibiotic cost. Complete remission at the end of induction chemotherapy and ECOG > 3 were independent prognostic factors for overall survival. In conclusion, R-M regimen is an effective and cost-effective combination treatment for PCNSLs, which warrants further evaluation in randomized trials.

Aberrantly Activated APOBEC3B Is Associated With Mutant p53-Driven Refractory/Relapsed Diffuse Large B-Cell Lymphoma.

Tumor protein 53 (TP53) mutation predicts an unfavorable prognosis in diffuse large B-cell lymphoma (DLBCL), but the molecular basis for this association remains unclear. In several malignancies, the cytidine deaminase apolipoprotein B mRNA editing enzyme catalytic subunit 3B (APOBEC3B) has been reported to be associated with the TP53 G/C-to-A/T mutation. Here, we show that the frequency of this mutation was significantly higher in relapsed/refractory (R/R) than in non-R/R DLBCL, which was positively associated with the APOBEC3B expression level. APOBEC3B overexpression induced the TP53 G/C-to-A/T mutation in vitro, resulting in a phenotype similar to that of DLBCL specimens. Additionally, APOBEC3B-induced p53 mutants promoted the growth of DLBCL cells and enhanced drug resistance. These results suggest that APOBEC3B is a critical factor in mutant p53-driven R/R DLBCL and is therefore a potential therapeutic target.

Efficacy and Safety of Nivolumab for Advanced Renal Cell Carcinoma: A Systematic Review and Meta-Analysis.

Objective: To assess the efficacy and safety of nivolumab for advanced renal cell carcinoma (RCC) via meta-analysis. Methods: In this systematic review and meta-analysis, we searched PubMed, Embase, Science Citation Index Expanded, The Cochrane Library, and Web of Science for randomized controlled trials (RCTs) using nivolumab for patients with advanced RCC published before 30 December 2021. Quality assessments and meta-analyses were performed on all the literature assessed for eligibility. Results: Of 203 studies identified as potentially eligible from 3214 studies in a preliminary search, three RCTs including 2550 RCC cases met the inclusion criteria and were of high quality. Meta-analysis showed benefits of nivolumab in the progression-free survival (PFS) (HR = 0.73, 95% CI: 0.54 to 0.99, P=0.04) and overall survival (OS) (HR = 0.70, 95% CI: 0.63 to 0.78, P < 0.001) of patients with advanced RCC, and no increase in documented adverse events was recorded. Conclusion: Nivolumab plus ipilimumab has significant benefits versus sunitinib in the treatment of advanced RCC in terms of tumor progression control and prolongation of OS and PFS, with a manageable safety profile.

FG-4592 alleviates radiation-induced intestinal injury by facilitating recovery of intestinal stem cell and reducing damage of intestinal epithelial.

Damage of Intestinal Stem Cells (ISCs) is the main cause of radiation induced-intestinal injury (RIII). Recently, hypoxia Inducible factor (HIF) was verified to be critical for promoting proliferation of ISCs, which suggested a protective role of HIF in the RIII. Thus, we investigated the effect of FG-4592, a novel up-regulator of HIF, on the protection of RIII. With/without FG-4592 treatment, the abdomen of mice was radiated, and intestinal injury was assessed. Especially, by intestinal organoid culture, the multiplication capacity and differentiation features of ISCs were detected. As a result, FG-4592, a novel up-regulator of HIF could remit RIII and promote regeneration and differentiation of ISCs after radiation, which were depended on HIF-2 rather than HIF-1.

Molecular Mechanisms of the RECQ4 Pathogenic Mutations.

The human RECQ4 gene encodes an ATP-dependent DNA helicase that contains a conserved superfamily II helicase domain located at the center of the polypeptide. RECQ4 is one of the five RECQ homologs in human cells, and its helicase domain is flanked by the unique amino and carboxyl termini with sequences distinct from other members of the RECQ helicases. Since the identification of the RECQ4 gene in 1998, multiple RECQ4 mutations have been linked to the pathogenesis of three clinical diseases, which are Rothmund-Thomson syndrome, Baller-Gerold syndrome, and RAPADILINO. Patients with these diseases show various developmental abnormalities. In addition, a subset of RECQ4 mutations are associated with high cancer risks, especially for osteosarcoma and/or lymphoma at early ages. The discovery of clinically relevant RECQ4 mutations leads to intriguing questions: how is the RECQ4 helicase responsible for preventing multiple clinical syndromes? What are the mechanisms by which the RECQ4 disease mutations cause tissue abnormalities and drive cancer formation? Furthermore, RECQ4 is highly overexpressed in many cancer types, raising the question whether RECQ4 acts not only as a tumor suppressor but also an oncogene that can be a potential new therapeutic target. Defining the molecular dysfunctions of different RECQ4 disease mutations is imperative to improving our understanding of the complexity of RECQ4 clinical phenotypes and the dynamic roles of RECQ4 in cancer development and prevention. We will review recent progress in examining the molecular and biochemical properties of the different domains of the RECQ4 protein. We will shed light on how the dynamic roles of RECQ4 in human cells may contribute to the complexity of RECQ4 clinical phenotypes.

Early Death and Survival of Patients With Acute Promyelocytic Leukemia in ATRA Plus Arsenic Era: A Population-Based Study.

Most randomized trials for acute promyelocytic leukemia (APL) have investigated highly selected patients under idealized conditions, and the findings need to be validated in the real world. We conducted a population-based study of all APL patients in Zhejiang Province, China, with a total population of 82 million people, to assess the generalization of all-trans retinoic acid (ATRA) and arsenic as front-line treatment. The outcomes of APL patients were also analyzed. Between January 2015 and December 2019, 1,233 eligible patients were included in the final analysis. The rate of ATRA and arsenic as front-line treatment increased steadily from 66.2% in 2015 to 83.3% in 2019, with no difference among the size of the center (≥5 or <5 patients per year, p = 0.12) or age (≥60 or <60 years, p = 0.35). The early death (ED) rate, defined as death within 30 days after diagnosis, was 8.2%, and the 3-year overall survival (OS) was 87.9% in the whole patient population. Age (≥60 years) and white blood cell count (>10 × 109/L) were independent risk factors for ED and OS in the multivariate analysis. This population-based study showed that ATRA and arsenic as front-line treatment are widely used under real-world conditions and yield a low ED rate and a high survival rate, which mimic the results from clinical trials, thereby supporting the wider application of APL guidelines in the future.

Chronic Progression of Lung Cancer Recurrence After Surgery: Warning Role of Postoperative Pneumonia.

PURPOSE: The association between the process of postoperative pneumonia and lung cancer recurrence remains elusive in lung cancer surgery. Herein, the association between postoperative pneumonia and lung cancer recurrence was investigated, emphasizing the warning role of postoperative specific pneumonia in primary lung cancer resection patients. METHODS: The occurrence of postoperative pneumonia was assessed in 4-6 months (PPFS), 7-12 months (PPST), and lung cancer recurrence within 1 year (LRO) in 332 patients. The primary outcome was the development of PPST and LRO according to PPFS occurrence. The relevant risk factors of PPFS, PPST, and LRO were identified through multivariable regression analysis. RESULTS: During follow-up, 151 (45.48%) participants experienced PPFS. Irrespective of the existing postoperative pneumonia in 1-3 months (PPOT), PPFS significantly increased the risk of PPST (P < 0.01) and LRO (P < 0.01), and persistent PPST further increased the risk of LRO (P < 0.001). The generalized estimating equation identified chemotherapy as an independent risk factor for PPFS and PPST. CONCLUSION: PPFS was associated with the increased risk of PPST and LRO. Postoperative pulmonary inflammation assessed 4 months post-surgery also significantly influenced LRO development, indicating a need for close follow-up of lung inflammatory conditions to improve patient outcomes.

Mutational landscape of thymic epithelial tumors in a Chinese population: insights into potential clinical implications.

BACKGROUND: Thymic epithelial tumors (TETs) are a heterogeneous group of rare malignancies which may be devastating, difficult to treat, and for which treatment options are limited. Herein, we investigated the comprehensive genomic alterations of TETs in a Chinese population for providing clinical management, especially targeted therapy. METHODS: Comprehensive genomic profiling (CGP) was performed with DNA targeted sequencing of cancer-associated genes (CSYS) from a cohort of 40 Chinese TET patients. TMB was measured by an in-house algorithm. MSI status was inferred based on the MANTIS (Microsatellite Analysis for Normal-Tumor InStability) score. The expression status of PD-L1 was estimated by immunohistochemistry. RESULTS: The mutational profiling of thymomas (Ts) and thymic neuroendocrine tumors (TNETs) showed scattered mutation distributions with no recurrently mutated genes. In contrast, thymic carcinomas (TCs) did show highly recurrent mutations including CDKN2A, CYLD, CDKN2B, and TP53. Among them, CDKN2A and CDKN2B mutations were the top potentially actionable alterations in TCs. PD-L1 expression was mainly present in Ts and TCs, and was predominant in males and smokers. CONCLUSIONS: Our study provided a comprehensive genetic alteration view on the largest Chinese cohort of TETs to date. The results identified different genomic mutational profiles of Ts, TCs, and TNETs, and analyzed potential druggable biomarkers with clinical implications in Chinese TET patients, which provided the evidence for precision medicine of rare TET patients.

Grape Seed Proanthocyanidins play the roles of radioprotection on Normal Lung and radiosensitization on Lung Cancer via differential regulation of the MAPK Signaling Pathway.

Radiation-induced lung injury (RILI) is a common serious complication and dose-limiting factor caused by radiotherapy for lung cancer. This study was to investigate radioprotective effects of grape seed proanthocyanidins (GSP) on normal lung as well as radiosensitizing effects on lung cancer. In vitro, we demonstrated radioprotective effects of GSP on normal alveolar epithelial cells (MLE-12 and BEAS/2B) and radiosensitizing effects on lung cancer cells (LLC and A549). In vivo, we confirmed these two-way effects in tumor-bearing mice. The results showed that GSP inhibited tumor growth, and played a synergistic killing effect with radiotherapy on lung cancer. Meanwhile, GSP reduced radiation damage to normal lung tissues. The two-way effects related to the differential regulation of the MAPK signaling pathway by GSP on normal lung and lung cancer. Moreover, GSP regulated secretion of cytokines IL-6 and IFN-γ and expression of p53 and Ki67 on normal lung and lung cancer. Our findings suggest that GSP is expected to be an ideal radioprotective drug for lung cancer patients who are treated with radiotherapy.

Inhibition of sestrin 1 alleviates polycystic ovary syndrome by decreasing autophagy.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, accounting for 50-70% of anovulatory infertility cases. However, the etiology of PCOS at the molecular level remains unclear. Here, bioinformatics analysis was performed to identify differentially expressed genes (DEGs) between adipose tissue of PCOS patients and matched tissues from non-hyperandrogenic women. RT-qPCR, western blot, cell counting kit-8 (CCK-8), EdU (5-Ethynyl-2'-deoxyuridine) staining, LC3 staining, ROS (reactive oxygen species) detection, and apoptosis assays were conducted to explore the effects of sestrin 1 on KGN human granulosa-like tumor cells. Bioinformatics analysis indicated that DEGs in adipose tissue from PCOS patients were enriched in the p53 signaling pathway. Moreover, sestrin 1 was identified as a major target of the p53 gene. Downregulation of sestrin 1 inhibited proliferation of KGN cells by inhibiting autophagy. Additionally, sestrin 1 downregulation increased ROS generation and promoted apoptosis in KGN cells. By contrast, overexpression of sestrin 1 increased cell viability by increasing autophagy in KGN cells. Together, these results suggest that downregulation of sestrin 1 may be a potential novel treatment strategy for PCOS.

Identification of a nine-gene prognostic signature for gastric carcinoma using integrated bioinformatics analyses.

BACKGROUND: Gastric carcinoma (GC) is one of the most aggressive primary digestive cancers. It has unsatisfactory therapeutic outcomes and is difficult to diagnose early. AIM: To identify prognostic biomarkers for GC patients using comprehensive bioinformatics analyses. METHODS: Differentially expressed genes (DEGs) were screened using gene expression data from The Cancer Genome Atlas and Gene Expression Omnibus databases for GC. Overlapping DEGs were analyzed using univariate and multivariate Cox regression analyses. A risk score model was then constructed and its prognostic value was validated utilizing an independent Gene Expression Omnibus dataset (GSE15459). Multiple databases were used to analyze each gene in the risk score model. High-risk score-associated pathways and therapeutic small molecule drugs were analyzed and predicted, respectively. RESULTS: A total of 95 overlapping DEGs were found and a nine-gene signature (COL8A1, CTHRC1, COL5A2, AADAC, MAMDC2, SERPINE1, MAOA, COL1A2, and FNDC1) was constructed for the GC prognosis prediction. Receiver operating characteristic curve performance in the training dataset (The Cancer Genome Atlas-stomach adenocarcinoma) and validation dataset (GSE15459) demonstrated a robust prognostic value of the risk score model. Multiple database analyses for each gene provided evidence to further understand the nine-gene signature. Gene set enrichment analysis showed that the high-risk group was enriched in multiple cancer-related pathways. Moreover, several new small molecule drugs for potential treatment of GC were identified. CONCLUSION: The nine-gene signature-derived risk score allows to predict GC prognosis and might prove useful for guiding therapeutic strategies for GC patients.

Pathogenic mutations reveal a role of RECQ4 in mitochondrial RNA:DNA hybrid formation and resolution.

The synthesis of mitochondrial DNA (mtDNA) is a complex process that involves the formation and resolution of unusual nucleic acid structures, such as RNA:DNA hybrids. However, little is known about the enzymes that regulate these processes. RECQ4 is a DNA replication factor important for mtDNA maintenance, and here, we unveil a role of human RECQ4 in regulating the formation and resolution of mitochondrial RNA:DNA hybrids. Mitochondrial membrane protein p32 can block mtDNA synthesis by restricting RECQ4 mitochondrial localization via protein-protein interaction. We found that the interaction with p32 was disrupted not only by the previously reported cancer-associated RECQ4 mutation, del(A420-A463), but also by a clinical mutation of the adjacent residue, P466L. Surprisingly, although P466L mutant was present in the mitochondria at greater levels, unlike del(A420-A463) mutant, it failed to enhance mtDNA synthesis due to the accumulation of RNA:DNA hybrids throughout the mtDNA. Biochemical analysis revealed that P466L mutation enhanced RECQ4 annealing activity to generate RNA:DNA hybrids at the same time reduced its unwinding activity to resolve this structure. Hence, P466L mutation led to a reduced efficiency in completing mtDNA synthesis due to unresolved RNA:DNA hybrids across mtDNA.

Bone age assessment based on deep convolution neural network incorporated with segmentation.

PURPOSE: Bone age assessment is not only an important means of assessing maturity of adolescents, but also plays an indispensable role in the fields of orthodontics, kinematics, pediatrics, forensic science, etc. Most studies, however, do not take into account the impact of background noise on the results of the assessment. In order to obtain accurate bone age, this paper presents an automatic assessment method, for bone age based on deep convolutional neural networks. METHOD: Our method was divided into two phases. In the image segmentation stage, the segmentation network U-Net was used to acquire the mask image which was then compared with the original image to obtain the hand bone portion after removing the background interference. For the classification phase, in order to further improve the evaluation performance, an attention mechanism was added on the basis of Visual Geometry Group Network (VGGNet). Attention mechanisms can help the model invest more resources in important areas of the hand bone. RESULT: The assessment model was tested on the RSNA2017 Pediatric Bone Age dataset. The results show that our adjusted model outperforms the VGGNet. The mean absolute error can reach 9.997 months, which outperforms other common methods for bone age assessment. CONCLUSION: We explored the establishment of an automated bone age assessment method based on deep learning. This method can efficiently eliminate the influence of background interference on bone age evaluation, improve the accuracy of bone age evaluation, provide important reference value for bone age determination, and can aid in the prevention of adolescent growth and development diseases.

Efficacy of Fe3O4@polydopamine nanoparticle-labeled human umbilical cord Wharton's jelly-derived mesenchymal stem cells in the treatment of streptozotocin-induced diabetes in rats.

Diabetes mellitus (DM) is characterized by the irreversible destruction of insulin-secreting pancreatic ß-islet cells and requires life-long exogenous insulin therapy. Umbilical cord Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) have been shown to improve islet function in animal models of diabetes. However, inadequate MSC homing to injured sites has limited their efficacy. Since efficient cell therapy heavily relies on appropriate homing to target tissues, increasing the specificity to the target organ and the extent of homing of the injected WJ-MSCs is paramount to successful clinical outcomes. Therefore, in this study, we synthesized Fe3O4@polydopamine nanoparticle (NP)-labeled MSCs and evaluated their therapeutic efficacy in a clinically relevant rat model of streptozotocin-induced diabetes using an external magnetic field. We found that NPs were successfully incorporated into WJ-MSCs and did not negatively affect stem cell properties. Magnetic targeting of WJ-MSCs contributed to long-term cell retention in pancreatic tissue and improved the islet function of diabetic rats, compared to injection of WJ-MSC alone. In addition, anti-inflammatory effects and the anti-apoptotic capacity of WJ-MSCs appeared to play a major role in the functional and structural recovery of the pancreas. Thus, therapy relying on the magnetic targeting of WJ-MSCs may serve as an effective approach for DM treatment.