From graphene to graphene ribbons: atomically precise cutting via hydrogenation pseudo-crack.

The properties and applications of graphene nanoribbons (GNRs) depend heavily on their shape and size, making precise design and construction at atomic scale significantly important. Herein, we show that pseudo-cracking is a feasible method for creating atomically precise GNRs. By using molecular dynamics (MD) simulation, we find that hydrogenation can act as a pseudo-crack to trigger the fracture of graphene along the hydrogenation line and cut the graphene into a GNR. Precise GNRs with a desired width, edge type and associated properties can be realized in a controllable way by manipulating the position and dimension of the hydrogenation pseudo-crack. We also find that it is better to use hydrogenation pseudo-cracks along the armchair direction to cut graphene at lower forces into GNRs with smooth edges. Our findings suggest a promising approach to cut graphene and other two-dimensional materials into nanoribbons effectively and accurately.

Alternative splicing of Ikaros regulates the FUT4/LeX-α5ß1 integrin-FAK axis in acute lymphoblastic leukemia.

Unveiling the mechanism of the relapse of acute lymphoblastic leukemia (ALL) is the key to improve the prognosis of ALL and remains a huge challenge. Glycan-based interactions play a vital role in immune surveillance, cell-cell adhesion and cell-matrix interaction, contributing to treatment failure in tumor. However, the glycan essential for leukemia development and its upstream regulatory mechanism by oncogenic drivers were rarely reported. Here, we demonstrated that LeX, a well-characterized cancer-related glycan epitope, strengthened the cell-matrix interaction via glycosylating α5ß1 integrin under the control of the driver oncogenic Ikaros isoform (IK6) in ALL. By analyzing the expression profile of Ikaros and the level of FUT4/LeX in clinical samples, we found that FUT4/LeX was positively correlated with dysfunctional Ikaros isoforms. IK1 (Full length Ikaros) regulates the level of FUT4 as a transcription repressor, while IK6 abolished the wild-type Ikaros mediated transcriptional repression and resulted in higher level of FUT4 expression. Moreover, we demonstrated that FUT4 could activate α5ß1-mediated sequential signal transduction and accelerate adhesion and invasion between integrin α5ß1 in leukemia cells and fibronectin in extracellular matrix (ECM) via increasing glycosylation. Together, our study provides a new insight into the mechanisms by which Ikaros mutation induced ALL cells invasion and a potential strategy for drug-resistance ALL by blocking LeX in combination with common chemotherapy.

[Analysis of clinical phenotype and TGM1 gene mutation in a child with neonatal congenital ichthyosis].

OBJECTIVE: To explore the genetic cause for a child with congenital ichthyosis. METHODS: The child was subjected to next generation sequencing using a specific gene panel. Suspected mutation was validated by Sanger sequencing. RESULTS: The proband was found to harbor compound heterozygous mutations c.327delG (p.Met109Ilefs*2) and c.791G>A (p.Arg264Gln) of the TGM1 gene, which were respectively inherited from his mother and father. The same mutations were not found among 101 healthy controls. c.327delG was not reported previously. By bioinformatic analysis, both mutations are likely to impair the function of TGase-1 protein. CONCLUSION: The compound heterozygous mutations of c.327delG and c.791G> A of the TGM1 gene probably underlie the ichthyosis in the proband. The result has facilitated prenatal diagnosis for this pedigree.

[Analysis of TCOF1 mutation in a Chinese patient with Treacher-Collins syndrome].

OBJECTIVE: To detect potential mutation of TCOF1 gene in a Chinese family affected with Treacher-Collins syndrome. METHODS: Clinical data of the patient was collected. The analysis included history taking, clinical examination and genetic testing. All coding regions of the TCOF1 gene were subjected to PCR amplification and Sanger sequencing. RESULTS: A novel mutation c.2261ins G (p.E95X) of the TCOF1 gene was discovered in the patient. The same mutation was not found in his parents and 100 healthy controls. CONCLUSION: The c.2261insG (p.E95X) mutation of the TCOF1 gene probably underlies the disease in the patient. Genetic testing can facilitate diagnosis and genetic counseling for families affected with TCS.

[Prevalence of Helicobacter pylori cagA, vacA, and iceA genotypes in children with gastroduodenal diseases].

OBJECTIVE: To investigate the prevalence of cagA, vacA, and iceA genotypes in the isolated strains of Helicobacter pylori (H.pylori) from children with gastroduodenal diseases in Jiangxi, China, as well as the association between cagA, vacA, and iceA genotypes and the type of gastroduodenal diseases. METHODS: The samples of gastric antral mucosa were collected from 316 children with gastroduodenal diseases in Jiangxi, and a total of 107 strains of H.pylori were isolated. The genomic DNA of these strains was extracted, and PCR was used to determine the ureA, cagA, vacA, and iceA genotypes. RESULTS: Of all the 107 isolated strains of H.pylori, the detection rates of ureA and cagA genes were 100% (107/107) and 94.4% (101/107) respectively. The overall detection rate of vacA gene was 100% (107/107), and the detection rates of vacAs1a, vacAs1c, vacAm1, and vacAm2 genes were 74.8% (80/107), 25.2% (27/107), 29.9% (32/107), and 69.2% (74/107) respectively, with both vacAm1 and vacAm2 genes detected in 0.9% (1/107) of all H.pylori strains. In the chimera of vacA gene, the detection rates of vacAs1a/m1, vacAs1a/m2, vacAs1c/m1, and vacAs1c/m2 genes were 26.2% (28/107), 51.4% (55/107), 3.7% (4/107), and 17.8% (19/107) respectively (P<0.001). The detection rates of iceA1 and iceA2 genes were 79.4% (85/107) and 9.3% (10/107), respectively (P<0.001), and both iceA1 and iceA2 genes were detected in 7.5% (8/107) of all strains. The detection rates of the genotypes of H.pylori showed no significant differences between the peptic ulcer, chronic gastritis, and duodenal bulbar inflammation groups (P>0.05). CONCLUSIONS: The dominant genotypes of H.pylori are cagA, vacAs1a/m2, and iceA1, and there are mixed infections with H.pylori strains of different genotypes in children with gastroduodenal disease from Jiangxi, China. The genotypes of H.pylori are not associated with the type of gastroduodenal disease.

The regulatory mechanisms of cerium oxide nanoparticles in oxidative stress and emerging applications in refractory wound care.

Cerium oxide nanoparticles (CeNPs) have emerged as a potent therapeutic agent in the realm of wound healing, attributing their efficacy predominantly to their exceptional antioxidant properties. Mimicking the activity of endogenous antioxidant enzymes, CeNPs alleviate oxidative stress and curtail the generation of inflammatory mediators, thus expediting the wound healing process. Their application spans various disease models, showcasing therapeutic potential in treating inflammatory responses and infections, particularly in oxidative stress-induced chronic wounds such as diabetic ulcers, radiation-induced skin injuries, and psoriasis. Despite the promising advancements in laboratory studies, the clinical translation of CeNPs is challenged by several factors, including biocompatibility, toxicity, effective drug delivery, and the development of multifunctional compounds. Addressing these challenges necessitates advancements in CeNP synthesis and functionalization, novel nano delivery systems, and comprehensive bio effectiveness and safety evaluations. This paper reviews the progress of CeNPs in wound healing, highlighting their mechanisms, applications, challenges, and future perspectives in clinical therapeutics.

Prognostic value of GLCE and infiltrating immune cells in Ewing sarcoma.

Background: The prognostic value of D-glucuronyl C5-epimerase (GLCE) and mast cell infiltration in Ewing sarcoma (ES) has not been well specified and highlighted, which may facilitate survival prediction and treatment. Methods: Several qualified datasets were downloaded from the GEO website. Common differentially expressed genes between normal subjects and ES patients in GSE17679, GSE45544, and GSE68776 were identified and screened by multiple algorithms to find hub genes with prognostic value. The prognostic value of 64 infiltrating cells was also explored. A prognostic model was established and then validated with GSE63155 and GSE63156. Finally, functional analysis was performed. Results: GLCE and mast cell infiltration were screened as two indicators for a prognostic model. The Kaplan‒Meier analysis showed that patients in the low GLCE expression, mast cell infiltration and risk score groups had poorer outcomes than patients in the high GLCE expression, mast cell infiltration and risk score groups, both in the training and validation sets. Scatter plots and heatmaps also indicated the same results. The concordance indices and calibration analyses indicated a high prediction accuracy of the model in the training and validation sets. The time-dependent receiver operating characteristic analyses suggested high sensitivity and specificity of the model, with area under the curve values between 0.76 and 0.98. The decision curve analyses suggested a significantly higher net benefit by the model than the treat-all and treat-none strategies. Functional analyses suggested that glycosaminoglycan biosynthesis-heparan sulfate/heparin, the cell cycle and microRNAs in cancer were upregulated in ES patients. Conclusions: GLCE and mast cell infiltration are potential prognostic indicators in ES. GLCE may affect the proliferation, angiogenesis and metastasis of ES by affecting the biosynthesis of heparan sulfate and heparin.

Fut7 Promotes Adhesion and Invasion of Acute Lymphoblastic Leukemia Cells through the Integrin/Fak/Akt Pathway.

Purpose: To investigate the role and mechanism of N-fucosyltransferase VII (FUT7) in acute lymphoblastic leukemia (ALL). Methods: Bone marrow tissues were collected from patients with ALL and children with immune thrombocytopenic purpura (control) hospitalized in our hospital during the same period. Then, the FUT7 expression in bone marrow tissues was detected by qRT-PCR and western blotting. Human ALL cell strain Jurkat was cultured, and after knockdown or overexpression of FUT7, cell proliferation, apoptosis, adhesion and invasion were examined by MTT assay, flow cytometry, fibronectin adhesion assay and transwell, respectively; the protein expression level of integrin α5, integrin ß1, p-FAK, and p-AKT was tested by western blotting. Results: The FUT7 expression was up-regulated in bone marrow cells of ALL patients. After knockdown of FUT7, the proliferation, adhesion and migration ability of ALL cells were significantly reduced, and apoptosis was increased, while the overexpression of FUT7 obtained the opposite results. Moreover, the overexpression of FUT7 also promoted the protein expression of integrin α5, integrin ß1, p-FAK, p-AKT. Conclusion: FUT7 can promote the adhesion and invasion of ALL cells by activating the integrin/FAK/AKT pathway.

A Posteriori Error Estimates for Fully Discrete Finite Element Method for Generalized Diffusion Equation with Delay.

In this paper, we derive several a posteriori error estimators for generalized diffusion equation with delay in a convex polygonal domain. The Crank-Nicolson method for time discretization is used and a continuous, piecewise linear finite element space is employed for the space discretization. The a posteriori error estimators corresponding to space discretization are derived by using the interpolation estimates. Two different continuous, piecewise quadratic reconstructions are used to obtain the error due to the time discretization. To estimate the error in the approximation of the delay term, linear approximations of the delay term are used in a crucial way. As a consequence, a posteriori upper and lower error bounds for fully discrete approximation are derived for the first time. In particular, long-time a posteriori error estimates are obtained for stable systems. Numerical experiments are presented which confirm our theoretical results.

[Expression of Ikaros and FUT4 in Children's Acute Lymphoblastic Leukemia and Their Relationship].

OBJECTIVE: To explore the possible molecular mechanism of Ikaros regulation on FUT4 expression by analyzing the correlation of the functional state of Ikaros with level of FUT4 expression, so as to provide the theoretical basis for personalized treatment in children with ALL. METHODS: The subtypes of Ikaros were identified by nested PCR and sequencing. The expression level of FUT4 was detected by quantitative PCR and analyzed by ΔΔCt method in the early stage of treatment, remission and relapse of ALL. RESULTS: Ik1 and Ik2 were the main functional subtypes, and the dominant negative Ikaros was Ik6; the Ik6 was detected in 23 patients with ALL. It was found that 2.73% patients expressing Ik6 alone and 18.18% patients with heterozygous expression were detected. The expression of FUT4 in the newly diagnosed ALL was higher than that in the control group, and the functional Ikaros negatively correlated with the FUT4 expression(r=-0.6329). CONCLUSION: Dominant negative Ikaros closely correlated with the relapse of acute lymphoblastic leukemia in children. The functional Ikaros negatively correlated with FUT4 expression. Ikaros inhibit the transcriptional activity of FUT4, that may be the molecular mechanism of Ikaros regulating the expression of FUT4.

[Role of p38MAPK signaling pathway in autophagy of Henle-407 cells induced by spvB of Salmonella typhimurium].

OBJECTIVE: To investigate the role of p38MAPK signaling pathway in autophagy of intestinal epithelial cells induced by spvB of S.typhimurium. METHODS: Henle-407 cells in exponential growth were infected with wild-type S.typhimurium strain STM-211 (with spvB gene), spvB mutated strain STM-delata;spvB, or with delata;spvB-complemented strain STM-c-spvB after treatment of the cells with the p38MAPK inhibitor SB203580. At different time points of co-culture, the cells were collected and the intracellular bacteria were counted. Western blotting was performed to detect the expressions of phosphorylated p38 and autophagy-related proteins LC3 and p62; immunofluorescence staining was used to observe the expression and distribution of LC3. RESULTS: At 1, 2 and 4 h after the infection, the phosphorylation levels of p38 in STM-211 group and STM-c-spvB group were significantly lower than that in STM-delata;spvB group (P<0.05). At 2 and 4 h of co-culture, the intracellular bacterial counts were significantly greater in STM-211 and STM-c-spvB infection groups than in STM-delata;spvB group (P<0.05). Pretreatment with p38 inhibitor SB203580 did no significantly affect the expression levels of LC3 II or P62 in STM-211 and STM-c-spvB groups, but caused significant reduction in their expressions in STM-delata;spvB group at 1 h (P<0.05), and such changes were more obvious at 3 h (P<0.05). CONCLUSION: The inhibitory effect of spvB gene on autophagy in intestinal epithelial cells is related with the negative regulation of p38MAPK signaling pathway.

Antifibrotic potential of bone marrow­derived mesenchymal stem cells in biliary atresia mice.

Biliary atresia (BA) is a rare and severe disease that affects infants where a fibroinflammatory process destroys the bile ducts, leading to fibrosis and biliary cirrhosis, and mortality if untreated. Bone marrow­derived mesenchymal stem cells (BMMSCs) have been considered as a promising therapy in fibrotic diseases. The aim of the present was to investigate the anti­fibrotic roles of BMMSC transplantation in a BA mouse model. Mouse BA models were established by Rhesus rotavirus administration to neonatal mice. The results revealed that the liver enzyme and bilirubin metabolism levels, and the levels of the oxidative stress marker malondialdehyde (MDA) and the fibrosis marker were all increased in the BA model, while the liver tissue levels of superoxide dismutase and glutathione peroxidase were reduced. The hematoxylin and eosin and Masson's trichrome staining revealed severe liver fibrosis and collagen accumulation in BA livers. However, these indicators were all reversed once the BA mice were administered the BMMSC inoculation. In conclusion, the present study demonstrated the anti­fibrotic potential of BMMSCs in BA mice, which may provide a novel approach to ameliorate the fibrotic response in BA patients.

[Nitrogen and phosphorus release from herbaceous vegetation under simulated inundation experiment of water-level fluctuation zone in the Three Gorges Reservior Area].

Nitrogen and phosphorus release from herbaceous vegetation of water-level fluctuation zone in the Three Gorges Reservior (TGR) area could become a crucial source which may deteriorate water quality of TGR. Stems and leaves of the dominant herbaceous plants from water-level fluctuation zone were collected and inundated in the laboratory for measuring nitrogen and phosphorus release along with decay process. Results show that: (1) The differences of initial carbon and nitrogen content among herbaceous plants of water-level fluctuation zone are remarkable, except intial phosphorus content. (2) The decomposition of vegetation under inundation causes the increase of pH, the decrease of Eh of the overlying water and the release of nitrogen and phosphorus. The release amount of total nitrogen (TN) and total phosphorus (TP) are (3.85 +/- 2.53), (1.33 +/- 0.73) mg x g(-1) respectively. The release process of TN and ammonia nitrogen (NH4(+) -N) shows a parabolic curve, whereas TP releases fits in a logarithmic curve. The average peak time of TN and TP concentration is in the 15th day of inundation, while NH4(+) -N is in the 33th day. The release amount and rate of nutrients follow the sequence in TN > TP > NH4(+) -N. The average loads of TN, TP and NH4(+) -N release from vegetation decay in three months' inundation are 22.4, 8.9 and 4.5 kg x hm(-2) respectively. (3) The lower initial C and higher initial N and P content of plant, make an advantage for nitrogen and phosphorus release when plants are inundated in flooding period of TGR.