LncRNA018392 promotes the proliferation of Liaoning cashmere goat skin fibroblasts by upregulating CSF1R through binding to SPI1.

BACKGROUND: Liaoning cashmere goat is recognized as a valuable genetic resource breed, with restrictions on genetic outflow in China. Hair follicle development in the cashmere goat is influenced by melatonin and long non-coding RNAs (lncRNAs). However, the role of lncRNAs in facilitating melatonin-promoted cashmere growth remains poorly understood. Previous studies have identified a new lncRNA, lncRNA018392, which is involved in the melatonin-promoted proliferation of cashmere skin fibroblasts. METHOD: Flow cytometry and CCK-8 assays confirmed that silencing lncRNA018392 negates the effects of melatonin on cell proliferation, and that proliferation was reduced when the gene CSF1R, located near lncRNA018392, was inhibited. Further investigation using a dual-luciferase reporter assay showed that lncRNA018392 could positively regulate the promoter of CSF1R. RESULTS: Results from RNA-binding protein immunoprecipitation (RIP) and chromatin immunoprecipitation sequencing (ChIP-Seq) revealed that lncRNA018392 interacts with the transcription factor SPI1, with CSF1R being a downstream target gene regulated by SPI1. This interaction was confirmed by ChIP-PCR, which demonstrated SPI1's binding to CSF1R. CONCLUSIONS: This study found that the melatonin-responsive lncRNA018392 accelerates the cell cycle and promotes cell proliferation by recruiting SPI1 to upregulate the expression of the neighboring gene CSF1R. These findings provide a theoretical foundation for elucidating the molecular mechanisms of cashmere growth and for the molecular breeding of cashmere goats.

Early prognostication of overall survival for pediatric diffuse midline gliomas using MRI radiomics and machine learning: A two-center study.

Background: Diffuse midline gliomas (DMG) are aggressive pediatric brain tumors that are diagnosed and monitored through MRI. We developed an automatic pipeline to segment subregions of DMG and select radiomic features that predict patient overall survival (OS). Methods: We acquired diagnostic and post-radiation therapy (RT) multisequence MRI (T1, T1ce, T2, and T2 FLAIR) and manual segmentations from 2 centers: 53 from 1 center formed the internal cohort and 16 from the other center formed the external cohort. We pretrained a deep learning model on a public adult brain tumor data set (BraTS 2021), and finetuned it to automatically segment tumor core (TC) and whole tumor (WT) volumes. PyRadiomics and sequential feature selection were used for feature extraction and selection based on the segmented volumes. Two machine learning models were trained on our internal cohort to predict patient 12-month survival from diagnosis. One model used only data obtained at diagnosis prior to any therapy (baseline study) and the other used data at both diagnosis and post-RT (post-RT study). Results: Overall survival prediction accuracy was 77% and 81% for the baseline study, and 85% and 78% for the post-RT study, for internal and external cohorts, respectively. Homogeneous WT intensity in baseline T2 FLAIR and larger post-RT TC/WT volume ratio indicate shorter OS. Conclusions: Machine learning analysis of MRI radiomics has potential to accurately and noninvasively predict which pediatric patients with DMG will survive less than 12 months from the time of diagnosis to provide patient stratification and guide therapy.

Prognostic value of body composition in patients with digestive tract cancers: A prospective cohort study of 8,267 adults from China.

BACKGROUND & AIMS: The characterization and prognostic value of body composition parameter/phenotype based on computed tomography (CT) in patients with digestive tract cancers remain incomplete. This study aimed to investigate the relationship between parameter/phenotype and clinical outcomes in patients with digestive tract cancers. METHODS: In this prospective cohort study, 8267 patients with digestive tract cancers were assessed using CT scans to determine body composition. Body composition data, including areas of skeletal muscle (SM), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT), were collected at the third lumbar level on CT images obtained within 30 days before surgery. Body composition phenotypes (sarcopenia, cancer cachexia, sarcopenic obesity) were determined based on SM, SAT, and VAT areas. The primary endpoint was overall survival, obtained from electronic medical records and telephone follow-up surveys. Kaplan-Meier and log-rank analyses were employed to compare unadjusted survival, while multivariate survival analyses were conducted using a proportional hazards model adjusted for age, gender, and cancer-node-metastasis (TNM) stages. RESULTS: Adjusted hazard ratios (HRs) for all-cause mortality were calculated for the second (Q2), third (Q3), and fourth (Q4) quantiles relative to the first quantile (Q1) for SM areas, revealing adjusted summary HRs of 0.575 (95% CI, 0.361-0.916), 0.419 (95% CI, 0.241-0.729), and 0.384 (95% CI, 0.203-0.726), respectively. Sarcopenia-adjusted summary HRs were 1.795 (95% CI: 1.012-3.181) for male patients and 1.925 (95% CI: 1.065-3.478) for female patients. Cancer cachexia-adjusted summary HRs were 1.542 (95% CI: 1.023-2.324) for male patients and 1.569 (95% CI: 0.820-3.001) for female patients. Sarcopenic obesity-adjusted summary HRs were 1.122 (95% CI: 0.759-1.657) for male patients and 1.303 (95% CI: 0.623-2.725) for female patients. Subgroup analyses indicated varying prognostic values of body composition parameter/phenotype among different cancer types. CONCLUSIONS: Our findings suggest a large SM area is a favorable prognostic indicator, while cancer cachexia and sarcopenia signify poor prognosis in patients with digestive tract cancers. These findings have important implications for the personalized preoperative assessment of body composition in patients with digestive tract cancers.

Dissecting microenvironment in cystadenomas and hepatic cysts based on single nucleus RNA-sequencing data.

Hepatic cystadenoma is a rare disease, accounting for about 5% of all cystic lesions, with a high tendency of malignant transformation. The preoperative diagnosis of cystadenoma is difficult, and some cystadenomas are easily misdiagnosed as hepatic cysts at first. Hepatic cyst is a relatively common liver disease, most of which are benign, but large hepatic cysts can lead to pressure on the bile duct, resulting in abnormal liver function. To better understand the difference between the microenvironment of cystadenomas and hepatic cysts, we performed single-nuclei RNA-sequencing on cystadenoma and hepatic cysts samples. In addition, we performed spatial transcriptome sequencing of hepatic cysts. Based on nucleus RNA-sequencing data, a total of seven major cell types were identified. Here we described the tumor microenvironment of cystadenomas and hepatic cysts, particularly the transcriptome signatures and regulators of immune cells and stromal cells. By inferring copy number variation, it was found that the malignant degree of hepatic stellate cells in cystadenoma was higher. Pseudotime trajectory analysis demonstrated dynamic transformation of hepatocytes in hepatic cysts and cystadenomas. Cystadenomas had higher immune infiltration than hepatic cysts, and T cells had a more complex regulatory mechanism in cystadenomas than hepatic cysts. Immunohistochemistry confirms a cystadenoma-specific T-cell immunoregulatory mechanism. These results provided a single-cell atlas of cystadenomas and hepatic cyst, revealed a more complex microenvironment in cystadenomas than in hepatic cysts, and provided new perspective for the molecular mechanisms of cystadenomas and hepatic cyst.

Poly-l-lysine modified MOF nanoparticles with pH/ROS sensitive CIP release and CUR triggered photodynamic therapy against drug-resistant bacterial infection.

The challenge of drug resistance in bacteria caused by the over use of biotics is increasing during the therapy process, which has attracted great attentions of the clinicians and scientists around the world. Recently, photodynamic therapy (PDT) triggered by photosensitizer (PS) has become a promising treatment method because of its high efficacy, easy operation, and low side effect. Herein, the poly-l-lysine (PLL) modified metal-organic framework (MOF) nanoparticles, ZIF/PLL-CIP/CUR, were synthesized to allow both reactive oxygen species (ROS) responsive drug release and photodynamic effect for synergistic therapy against drug resistant bacterial infections. The PLL was modified on the shell of the zeolite imidazole framework (ZIF) by the ROS-responsive thioketal linker for controllable CIP release. CUR were encapsulated in ZIF as the photosensitizer for blue light mediated photodynamic effect to produce singlet oxygen (1O2) and superoxide anion radical (O2-) for efficient inhibition towards methicillin-resistant Staphylococcus aureus (MRSA). The charge conversion from negative charge (-4.6 mV) to positive charge (2.6 mV) was observed at pH 7.4 and pH 5.5, and 70.9 % CIP was found released at pH 5.5 in the presence of H2O2, which suggests the good biosafety at physiological pH and ROS-responsive drug release of the as-prepared nanoparticle in the bacterial microenvironment. The as-prepared nanoparticles could effectively kill MRSA and disrupt bacterial biofilm by combination of chemo- and photodynamic therapy. In mice model, the as-prepared nanoparticles exhibited excellent biosafety and synergistic effect with 98.81 % healing rate in treatment of MRSA infection, which is considered as a promising candidate in combating drug resistant bacterial infection.

Inclusion complex of quercetin with sulfobutylether ß-cyclodextrin: preparation, characterization, antioxidant and antibacterial activities and the inclusion mechanism.

Quercetin (QCT) has a variety of pharmacological effects, such as antioxidant, antibacterial, anticancer, anticardiovascular and antiaging effects. However, its poor water solubility, stability and bioavailability limit its applications. The special structure of cyclodextrins and their derivatives with a hydrophobic inner cavity and hydrophilic outer wall can load a variety of hydrophobic drugs of a suitable size and shape, thereby improving the stability and solubility of these molecules. In this study, an inclusion complex of quercetin and sulfobutylether-ß-cyclodextrin was prepared. It was characterized via FT-IR, UV, 1H NMR, XRD, DSC, and SEM analysis, which revealed the successful formation of the inclusion complex. In vitro biological activity estimations were carried out and the results indicated that the inclusion complex displayed higher antioxidative and antibacterial properties compared with free QCT. In addition, the mechanisms of inclusion were explored using 1H NMR analysis and docking calculations, thus providing a theoretical basis for obtaining an inclusion complex.