Everolimus inhibits hepatoblastoma by inducing autophagy-dependent ferroptosis.

Everolimus, a known inhibitor of the mammalian target of rapamycin (mTOR), has shown uncertain efficacy in treating hepatoblastoma. This study delves into the potential anti-hepatoblastoma properties of everolimus and its intricate relationship with autophagy and ferroptosis, both in vitro and in vivo. In vivo, tumor tissue from hepatoblastoma patient and human hepatoblastoma cell line HuH-6 were xenografted into nude mice to establish xenograft models for observing the effect of everolimus on tumor growth. In vitro, HuH-6 cells were cultured to evaluate the anti-hepatoblastoma activity of everolimus. Transmission electron microscopy and microtubule-associated proteins 1 light chain 3 (LC3), beclin 1, and p62 protein expressions were employed to investigate autophagy. Additionally, indicators of cell apoptosis, reactive oxygen species (ROS) and proteins associated with ferroptosis were measured to evaluate ferroptosis. The results demonstrate that everolimus treatment effectively induced the formation of autophagosomes in hepatoblastoma cells, upregulated the LC3II/I ratio and beclin 1 expression, and downregulated p62 expression, indicating an enhanced autophagy level both in vitro and in vivo. Furthermore, everolimus treatment induced cell apoptosis, increased ROS level, elevated concentrations of malondialdehyde, 4-hydroxynonenal, and iron content, while reducing the ratio of glutathione/oxidized glutathione, and downregulating the protein expression of glutathione peroxidase 4 and solute carrier family 7 member 11, suggesting its ability to induce ferroptosis in hepatoblastoma cells. Importantly, the induction of ferroptosis by everolimus was significantly reversed in the presence of autophinib, an autophagy inhibitor, indicating the autophagy-dependent of everolimus-induced ferroptosis. Taken together, these findings suggest that everolimus holds promise as an effective anti-hepatoblastoma drug, with its mechanism of action potentially involving the induction of autophagy-dependent ferroptosis in hepatoblastoma cells.

Patent vitellointestinal duct with ileal prolapse in a newborn: A case report and literature review.

RATIONALE: Patent vitellointestinal duct is the most common omphalomesenteric duct anomaly to present with symptoms. PATIENT CONCERNS: A 10-day-old child presented with increase in the size of a polypoidal lesion into a large, "Y"-shaped reddish, prolapsing lesion, discharging gaseous, and fecal matter at her umbilicus. A laparoscopic exploration was performed, followed by wedge resection and anastomosis. No complications occurred during postoperative follow-up. DIAGNOSES: A patent vitellointestinal duct with ileal prolapse. INTERVENTIONS: The resection of extended intraperitoneal intestinal tube was performed. OUTCOMES: During the follow-up 3 months after surgery, the umbilical cord of the child healed well after surgery. LESSONS: Timely surgical treatment can minimize the occurrence of complications, and the overall prognosis is good after surgery.

Upregulation of the Four and a Half LIM Domains 1 linked with familial venous dysplasia in a familial genetic examination.

BACKGROUND: This study aimed to analyze the mutation site in a family diagnosed with venous dysplasia to identify possible pathogenic genes. METHODS: A 15-year-old female presented with lower extremity venous tortuosity aggravated by ulceration. Only the young sister exhibited similar symptoms within the immediate family of the proband. Whole genome sequencing (WGS) was used to evaluate the mutation sites and chromosome copy number variations (CNV) within the family. The possible pathogenic genes located in the region with CNVs were identified, and the expression of the possible pathogenic genes was verified via quantitative polymerase chain reaction (Q-PCR) and western blotting (WB) analysis. In-vitro models were used to verify the role of possible pathogenic genes linked with the development of venous dysplasia. RESULTS: The high-resolution karyotype analysis of the chromosomes found no abnormalities. The results of the WGS indicated that the proband and her sister shared the CNV events, including a microdeletion on chromosomes X: 13580000-1358555000 and microduplications of chromosome X: 136055000-136290000, chromosome X: 136475000-13671000. The results of the Q-PCR and WB showed that FHL1 was highly expressed in the proband and her sister, indicating that mutations of the FHL1 may have an important role in the development of vein malformations. The results of the in vitro experiments showed that FHL1 overexpression could inhibit venous development. CONCLUSION: The CNV in the Xq26 region (136054501-136288300) was found to be linked with the development of venous malformations in this family. However, further studies are required to evaluate the genetic mechanisms involved in the development of venous malformations.

Development of a digital imaging analysis system to evaluate the treatment response in superficial infantile hemangiomas.

Superficial infantile hemangiomas (IH) are benign vascular tumors common in children characterized by bright red "strawberry" lesions on the skin. In order to optimize the treatment for this disease, there is a need to develop objective tools to assess treatment response. Since a color change in the lesion is a good indicator of treatment response, we have developed a digital imaging system to quantify the values of red, green, and blue (RGB) difference and RGB ratio between the tumor and normal tissue to take into account the variations in color between different skin types. The efficacy of the proposed system in assessing treatment response in superficial IH was evaluated in relation to established visual and biochemical tools used to grade hemangiomas. As the treatment progressed, the RGB ratio was almost 1, while the RGB difference was close to 0, which indicates a good response to treatment. There was a strong correlation between the RGB score and the other visual grading systems. However, the correlation between the RGB scoring system and the biochemical method was weak. These findings suggest that the system can be used clinically to objectively and accurately evaluate disease progression and treatment response in patients diagnosed with superficial IH.

Study of the low temperature oxidation of propane.

The low-temperature oxidation of propane was investigated using a jet-stirred reactor at atmospheric pressure and two methods of analysis: gas chromatography and synchrotron vacuum ultraviolet photoionization mass spectrometry (SVUV-PIMS) with direct sampling through a molecular jet. The second method allowed the identification of products, such as molecules with hydroperoxy functions, which are not stable enough to be detected by gas chromatography. Mole fractions of the reactants and reaction products were measured as a function of the temperature (530-730 K), with a particular attention to reaction products involved in the low temperature oxidation, such as cyclic ethers, aldehydes, alcohols, ketones, and hydroperoxides. A new model has been obtained from an automatically generated one, which was used as a starting point, with a large number of re-estimated thermochemical and kinetic data. The kinetic data of the most sensitive reactions, i.e., isomerizations of alkylperoxy radicals and the subsequent decompositions, have been calculated at the CBS-QB3 level of theory. The model allows a satisfactory prediction of the experimental data. A flow rate analysis has allowed highlighting the important reaction channels.

Experimental and modeling investigation of the low-temperature oxidation of n-heptane.

The low-temperature oxidation of n-heptane, one of the reference species for the octane rating of gasoline, was investigated using a jet-stirred reactor and two methods of analysis: gas chromatography and synchrotron vacuum ultra-violet photo-ionization mass spectrometry (SVUV-PIMS) with direct sampling through a molecular jet. The second method allowed the identification of products, such as molecules with hydroperoxy functions, which are not stable enough to be detected using gas chromatography. Mole fractions of the reactants and reaction products were measured as a function of temperature (500-1100K), at a residence time of 2s, at a pressure of 800 torr (1.06 bar) and at stoichiometric conditions. The fuel was diluted in an inert gas (fuel inlet mole fraction of 0.005). Attention was paid to the formation of reaction products involved in the low temperature oxidation of n-heptane, such as olefins, cyclic ethers, aldehydes, ketones, species with two carbonyl groups (diones) and ketohydroperoxides. Diones and ketohydroperoxides are important intermediates in the low temperature oxidation of n-alkanes but their formation have rarely been reported. Significant amounts of organic acids (acetic and propanoic acids) were also observed at low temperature. The comparison of experimental data and profiles computed using an automatically generated detailed kinetic model is overall satisfactory. A route for the formation of acetic and propanoic acids was proposed. Quantum calculations were performed to refine the consumption routes of ketohydroperoxides towards diones.

A comprehensive role evaluation and mechanism exploration of POGLUT2 in pan-cancer.

Objective: To evaluate the role of POGLUT2 in pan-cancer through bioinformatics analysis and experimental verification. Methods: Expression, gene mutation and amplification, methylation, and copy number alteration (CNA) of POGLUT2 were evaluated using The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), and Genotype-Tissue Expression (GTEx) databases. Moreover, POGLUT2 on survival and disease progression in pan-cancer was performed using TCGA data. Immune infiltration and tumor microenvironment evaluations were assessed by ImmuneScore, ImmuCellAI, and TIMER databases. POGLUT2 correlated drug resistance analysis was performed using the GDSC2 database. Furthermore, POGLUT2 knockdown of breast cancer cells was established, followed by in vitro biological function assays and in vivo tumor growth study. The mechanisms of POGLUT2 in breast cancer were briefly evaluated via its connection with Notch signaling. Results: Increased levels of POGLUT2 were found in multiple types of cancer tissues and cell lines. Moreover, increased gene mutation and amplification, methylation, and CNA of POGLUT2 were found in several types of cancers. POGLUT2 was mainly expressed in stromal cells as verified by StromalScore, ESTIMATEScore, ImmuneScore, and Tumor purity, and POGLUT2 was positively correlated with cancer-associated fibroblasts, macrophages, monocytes, and neutrophils in the tumor microenvironment. In vitro and in vivo results showed that POGLUT2 knockdown could delay tumor growth and progression. Notch signaling components were related to the function of POGLUT2. Conclusions: Increased levels of POGLUT2 could result in the dysregulated immune cell infiltration and tumor microenvironment and showed a significant regulatory effect on the progression of breast cancer through Notch-related signaling.

MALAT1 modulates alternative splicing by cooperating with the splicing factors PTBP1 and PSF.

Understanding how long noncoding RNAs (lncRNAs) cooperate with splicing factors (SFs) in alternative splicing (AS) control is fundamental to human biology and disease. We show that metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a well-documented AS-implicated lncRNA, regulates AS via two SFs, polypyrimidine tract-binding protein 1 (PTBP1) and PTB-associated SF (PSF). MALAT1 stabilizes the interaction between PTBP1 and PSF, thereby forming a functional module that affects a network of AS events. The MALAT1-stabilized PTBP1/PSF interaction occurs in multiple cellular contexts; however, the functional module, relative to MALAT1 only, has more dominant pathological significance in hepatocellular carcinoma. MALAT1 also stabilizes the PSF interaction with several heterogeneous nuclear ribonucleoparticle proteins other than PTBP1, hinting a broad role in AS control. We present a model in which MALAT1 cooperates with distinct SFs for AS regulation and pose that, relative to analyses exclusively performed for lncRNAs, a comprehensive consideration of lncRNAs and their binding partners may provide more information about their biological functions.

Detailed product analysis during the low temperature oxidation of n-butane.

The products obtained from the low-temperature oxidation of n-butane in a jet-stirred reactor (JSR) have been analysed using two methods: gas chromatography analysis of the outlet gas and reflectron time-of-flight mass spectrometry. The mass spectrometer was combined with tunable synchrotron vacuum ultraviolet photoionization and coupled with a JSR via a molecular-beam sampling system. Experiments were performed under quasi-atmospheric pressure, for temperatures between 550 and 800 K, at a mean residence time of 6 s and with a stoichiometric n-butane/oxygen/argon mixture (composition = 4/26/70 in mol%). 36 reaction products have been quantified, including in addition to the usual oxidation products, acetic acid, hydrogen peroxide, C(1), C(2) and C(4) alkylhydroperoxides and C(4) ketohydroperoxides. Evidence of the possible formation of products (dihydrofuranes, furanones) derived from cyclic ethers has also been found. The performance of a detailed kinetic model of the literature has been assessed with the simulation of the formation of this extended range of species. These simulations have also allowed the analysis of possible pathways for the formation of some obtained products.

Pyrolysis of n-heptane: experimental and theoretical study.

An experimental study of n-heptane pyrolysis (2.0% n-heptane in argon) has been performed at low pressure (400 Pa) within the temperature range from 780 to 1780 K. The pyrolysis products were detected by using synchrotron vacuum ultraviolet photoionization mass spectrometry (SVUV-PIMS). Photoionization mass spectra and photoionization efficiency spectra were measured to identify pyrolysis products, especially radicals and isomers. Mole fraction profiles of pyrolysis products versus temperature were also measured, indicating that H(2), CH(4), C(2)H(2), and C2-C6 alkenes are major pyrolysis products of n-heptane. Meanwhile, the thermal decomposition pathways of n-heptane have been investigated using theoretical calculation. The calculation results are in good agreement with the experimental measurement. On the basis of the experimental observation and theoretical calculation, the pyrolysis channels of unimolecular dissociation are proposed to understand the pyrolysis process of n-heptane.

LncRNA SNHG8 Serves as an Oncogene in Breast Cancer Through miR-634/ZBTB20 Axis.

BACKGROUND: Small nucleolus RNA Host Gene 8 (SNHG8) belongs to a subgroup with long non-coding RNAs. LncRNA SNHG8 presents up-regulated in miscellaneous cancers, like gastric cancer, liver cancer, and esophageal squamous cell cancer. Nevertheless, the expression pattern and the pathological function of lncRNA SNHG8 in breast cancer remain obscure. METHODS: We examined the expression levels of lncRNA SNHG8 in the tissue samples and cell lines from breast cancer via RT-qPCR in the present study. The functions of lncRNA SNHG8 on the progression of breast cancer cell were examined by CCK-8, EdU, Transwell chamber assays, and flow cytometry analyses. The expression of proteins was assessed using Western blot assay. RESULTS: We found that proliferation, migration, and invasion of breast cancer cells were significantly inhibited due to knockdown of lncRNA SNHG8, while inducing apoptosis of these cells. Mechanistically, SNHG8 functioned as an inhibitor of miR-634 in tumor tissues. CONCLUSION: LncRNA SNHG8 sponged the miR-634 to increase the expression level of ZBTB20, thus further aggravating the malignancy of breast cancer. Hence, the lncRNA SNHG8-miR-634-ZBTB20 axis may be a promising therapeutic target to treat breast cancers.

Determination of absolute photoionization cross-sections of alkanes and cyclo-alkanes.

Absolute photoionization and dissociative photoionization cross-sections of eleven n-alkanes (n-pentane, n-hexane, n-heptane, n-nonane, n-decane, n-undecane, n-dodecane, n-tridecane, n-tetradecane, n-pentadecane and n-hexadecane), three cyclo-alkanes (cyclopentane, methylcyclohexane and trans-decahydronaphthalene) and iso-octane were measured for photon energies from the ionization thresholds to 11.5 eV. The measurements were performed with the binary-liquid-mixture method utilizing the photoionization cross-sections of benzene as a calibration standard. The ionization energies of n-alkanes and cyclo-alkanes were also calculated at the B3P86/6-31 + +G(d,p) level and by the G3B3 method.

Anti-cancer peptides: classification, mechanism of action, reconstruction and modification.

Anti-cancer peptides (ACPs) are a series of short peptides composed of 10-60 amino acids that can inhibit tumour cell proliferation or migration, or suppress the formation of tumour blood vessels, and are less likely to cause drug resistance. The aforementioned merits make ACPs the most promising anti-cancer candidate. However, ACPs may be degraded by proteases, or result in cytotoxicity in many cases. To overcome these drawbacks, a plethora of research has focused on reconstruction or modification of ACPs to improve their anti-cancer activity, while reducing their cytotoxicity. The modification of ACPs mainly includes main chain reconstruction and side chain modification. After summarizing the classification and mechanism of action of ACPs, this paper focuses on recent development and progress about their reconstruction and modification. The information collected here may provide some ideas for further research on ACPs, in particular their modification.

Determination of absolute photoionization cross-sections of aromatics and aromatic derivatives.

The absolute photoionization cross-sections of aromatics and aromatic derivatives including toluene, ethylbenzene, n-propylbenzene, o-xylene, m-xylene, p-xylene, 1,3,5-trimethylbenzene, styrene, phenylacetylene, indene, indane, 1-methylnaphthalene, benzyl alcohol and benzaldehyde were measured at the photon energy range from ionization thresholds to 11.7 eV. The experiments were performed by tunable synchrotron vacuum ultraviolet (VUV) photoionization mass spectrometry. Benzene was chosen as a calibration standard, since its photoionization cross-section is well known. Binary liquid mixtures of the investigated molecules and benzene were used in the measurements. Photo-induced fragments from the molecules were also observed, and their photoionization cross-sections are also presented.

NEW EXPERIMENTAL EVIDENCES ABOUT THE FORMATION AND CONSUMPTION OF KETOHYDROPEROXIDES.

The formation of hydroperoxides postulated in all the kinetic models for the low temperature oxidation of alkanes have been experimentally proved thanks to a new type of apparatus associating a quartz jet-stirred reactor through a molecular-beam sampling system to a reflectron time-of-flight mass spectrometer combined with tunable synchrotron vacuum ultraviolet photoionization. This apparatus has been used to investigate the low-temperature oxidation of n-butane and has allowed demonstrating the formation of different types of alkylhydroperoxides, namely methylhydroperoxide, ethylhydroperoxide and butylhydroperoxide, and of C4 alkylhydroperoxides including a carbonyl function (ketohydroperoxides). In addition, the formation of products deriving from these ketohydroperoxides, such as C4 molecules including either two carbonyl groups or one carbonyl and one alcohol functions, has been observed. Simulations using a detailed kinetic model have been performed to support some of the assumptions made in this work.