Metal-organic frameworks (MOFs) are crystalline materials with a multidimensional porous network structure, formed through coordination bonds with metal ions as nodes and organic ligands as connecting bridges. Due to their excellent physicochemical properties, MOFs have extensive applications in the field of biomedicine, ranging from antibacterials, drug carriers, imaging to sensors. Nanoscale metal-organic frameworks (nMOFs), commonly utilized drug carriers, can gain enhanced safety, targeted delivery, and superior therapeutic effect through endocytosis. In this review, we comprehensively summarize the factors influencing the endocytosis of nMOFs, focusing on three key physicochemical properties, particle size, morphology and surface modification. Based on different illness models, the review succinctly summarizes the latest advancements in understanding the endocytosis pathways of nMOFs while critically reflecting on the inherent limitations of current research methods. Lastly, the review offers valuable insights into future research methodologies and objectives, aiming to lay the groundwork and provide meaningful guidance for the synthesis and development of nMOFs as promising versatile drug carriers.

Objective To elucidate the clinical significance of high expression levels of endonuclease meiosis 1(EME1)in the prognosis of hepatocellular carcinoma(HCC).Methods The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases were used to screen and analyze differential gene expression between HCC and non-tumor tissues.A retrospective collection of liver tissue samples from 80 HCC patients who underwent hepatectomy in the Fifth Medical Center of Chinese PLA General Hospital between January 2010 and December 2014 was performed.Immunohistochemistry analysis was employed to detect the EME1 expression levels.Survival analysis was then conducted to assess the impact of EME1 expression on 5-year postoperative survival rate of HCC patients.Additionally,gene enrichment analysis was applied to predict the function of EME1 in HCC.Results A total of 371 HCC tissue samples and 50 non-tumor liver tissue samples from TCGA database were analyzed,revealing significantly higher EME1 expression in HCC tissues.Microarray analysis of 107 samples within the GEO database(70 HCC tissues and 37 non-tumor tissues)confirmed that EME1 mRNA expression was markedly elevated in HCC tissues compared with non-tumor tissues(P<0.05).The 5-year overall survival(OS)rate was notably lower in high EME1 expression group than that in low expression group(44.1%vs.53.0%,P<0.05).Semi-quantitative immunohistochemistry analysis demonstrated that patients with high EME1 expression had a significantly lower OS rate than those with low EME1 expression(32.8%vs.45.0%,P<0.05).Multivariate COX regression analysis identified that high EME1 expression(HR=2.234,95%CI 1.073-4.649,P=0.032)and advanced China liver caner(CNLC)staging(HR=4.317,95%CI 1.799-10.359,P=0.001)were independent risk factors for the 5-year OS of post-operation patients with HCC.Conclusion Elevated EME1 expression in HCC tissues correlates with an adverse prognosis of HCC and suggests that EME1 could serve as a potential therapeutic target for HCC.

Background::Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid ( GSC) has been implicated in cancer development. However, the comprehensive biological role of GSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role of GSC in PCa development. Methods::We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression of GSC and its association with patient prognosis, and identified GSC-relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis of GSC in PCa. To understand the transcriptional regulation of GSC by E2F transcription factor 1 ( E2F1), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib. Results::GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations of GSC contribute to the progression of various tumors especially in PCa. Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further, GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor, E2F1, stimulates GSC by binding to its promoter region. Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment. Conclusions::GSC was highly overexpressed and strongly correlated with patient prognosis in PCa. We found that GSC, regulated by E2F1, acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.

OBJECTIVE: To explore clinical efficacy of congenital brachymetatarsia with immediate metatarsal lengthening. METHODS: From March 2015 to December 2020, 7 patients with brachymetatarsia were treated, including 6 females and 1 male;aged range from 18 to 30 years old;there were 5 patients with metatarsal microsomia on one foot, 2 patients with metatarsal microsomia on the first and fourth right foot, and immediate extension of metatarsal microsomia on the first and fourth right foot;two patients were short metatarsal bones of both feet. The length of short metatarsal bone, length of normal metatarsal bone, distance of short metatarsal bone and healing of bone graft were observed before and 12 months after operation. American Orthopaedic Foot and Ankle Society (AOFAS) scores were used to evaluate clinical efficacy and observe complications. RESULTS: Seven patients were followed up for 12 to 24 months. All metatarsal bones were extended to satisfactory length and bone graft were healed completely. Metatarsal length and shortening distance were improved from 3.55 to 5.90 cm and 0.77 to 1.46 cm before operation to 4.31 to 6.87 cm and 0.04 to 0.57 cm at 12 months after operation. Postoperative X-ray of the affected foot at 12 months showed bone healing was achieved between metatarsal bone and bone graft in 7 patients, and the parabolic shape of the distal metatarsal bone recovered after operation. AOFAS scores improved from 40 to 70 before operation to 88 to 95 points at 12 months after operation, and 6 patients were excellent and 1 good. CONCLUSION Immediate extension of metatarsal bone for congenital brachymetatarsia, the transplanted bone grew well during the process of bone grafting healing, the occurrence of bone nonunion was reduced, the short metatarsal bone was restored to a satisfactory length, and the toe function restored well.
Humans ; Female ; Male ; Metatarsal Bones/abnormalities* ; Adult ; Adolescent ; Young Adult ; Bone Lengthening/methods* ; Foot Deformities, Congenital/surgery*

Infant, Newborn ; Humans ; Macrophage Activation Syndrome/diagnosis*

ObjectiveTo reveal the differences of the related pathogenicity gene mutations between sebaceous adenocarcinoma （SC） of scalp and sebaceous adenoma （SA） of scalp on whole exome level. MethodsWhole exome sequencing was performed on a SC sample and a SA sample by Illumina Hiseq 2500 platform. Suspicious single nucleotide variation sites were selected for mutation conservation and functional analysis. SciClone was used to track subclone evolution and clonal map information was obtained for each tumor sample. The high-frequency significant gene mutations in the tumor sample were screened by MutSigCV software， and compared with the known driver genes. ResultsTwo driver genes TFDP1 and ACVR1B harboring mutations in scalp SC compared to SA were found. ConclusionsThe finding of mutation in driver genes TFDP1 and ACVR1B should be confirmed in a large cohort， which might reveal the mechanism of scalp SC development and find a therapeutic target for SC.

Acute myeloid leukemia (AML) is a genetic heterogeneous disease in which primordial and juvenile myeloid cells proliferate or accumulate abnormally in bone marrow, peripheral blood and other tissues, resulting in damage to normal hematopoietic function. Studies have shown that about 30% of AML patients have FMS-like tyrosine kinase 3 (FLT3), FLT3 abnormal regulation is closely related to the occurrence and development of AML. At present, FLT3 has become an important target for developing small molecular targeted drugs. Currently, a variety of FLT3 inhibitors and FLT3 degraders have been developed targeting FLT3, and some compounds have exhibited good anti-AML activity. This article summarizes and sorts out the current mainstream drugs for AML therapeutic targeting FLT3, in order to provide a reference for the development and design of AML drugs.