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Background: Acute lymphoblastic leukemia with MLL/AF4 rearrangement remains a major hurdle to improving outcomes. Gene network and circRNAs have been found to participate in tumorigenesis, while their roles in leukemia still need to be explored. Recent patents have shown that circRNAs exhibit the markers for the children ALL, although the target and related mechanism remain to be elucidated. Objective: This study aims to explore the possible targets and mechanisms of ALL with MLLAF4 rearrangement. Methods: We first generated a gene network focusing on MLL-AF4 rearrangement. Cell viability was determined with Cell Counting Kit-8 assay. The cell apoptosis was tested by the Annexin V/PI assay. The RNA-protein complexes were analyzed by qRT-PCR, and the pathway proteins were analyzed by western blot. Results: This gene network was associated with biological processes, such as nucleic acid metabolism and immunity, indicating its key role in inflammation. We found that circ_0008012 was upregulated in MLL/AF4 ALL cells and regulated cell proliferation and apoptosis. Further computed simulation and RIP showed that IKKβ was the strongest protein in the NF-κB pathway binding with circ_0008012. As a result, possible regulation of circ_0008012 is suggested by binding IKKβ in the IKKα:IKKβ:IKKγ compound, which then phosphorylates IκB and activates NF- κB:p65:p300 compound in cell nucleus, thereby leading to leukemia. Conclusion: We identified a gene network for MLL/AF4 ALL. Moreover, circ_0008012 may be a therapeutic target for this subtype of ALL.

Rechargeable magnesium batteries (RMBs) are considered as potential energy storage devices due to their high volumetric specific capacity, good safety, as well as source abundance. Despite extensive efforts devoted to constructing an efficient magnesium battery system, the sluggish Mg

5-AZA-DC is an efficient methylation inhibitor that inhibits methylation of target DNA. In this study, we explored the effects of 5-AZA-DC on the regulation of TGFβ1 on target genes in neuroglial cell, as well as neuroglial cell functions under oxidative stress. The oxidative stress was constructed by editing CRISPR/Cas9 for knock out Ang-1 and ApoE4 genes. Cells were subjected to TGFβ1OE (or shTGFβ1) transfection and/or 5-AZA-DC intervention. Results showed that under oxidative stress, both TGFβ1OE and shTGFβ1 transfection raised DNMT1, but reduced TGFβ1, PTEN, and TSC2 expressions in neuroglial cells. TGFβ1 directly bind to the promoter of PTEN gene. 5-AZA-DC intervention lowered DNMT1 and raised TGFβ1 expression, as well as promoted the binding between TGFβ1 and promoter of PTEN. TGFβ1OE caused a significant increase in the DNA demethylation level of PTEN promoter, while 5-AZA-DC intervention reduced the DNA demethylation level of PTEN promoter. Under oxidative stress, TGFβ1OE (or shTGFβ1) transfection inhibited neuroglial cell proliferation, migration, and invasion, promoted cell apoptosis. 5-AZA-DC intervention alleviated TGFβ1OE (or shTGFβ1) transfection caused neuroglial cell proliferation, migration, and invasion inhibition, as well as cell apoptosis. To conclude, these results suggest that 5-AZA-DC can be used as a potential drug for epigenetic therapy on oxidative stress damage in neuroglial cells. The findings of this research provide theoretical basis and research ideas for methylation drug intervention and TGFβ1 gene as a possible precise target of glial oxidative stress diagnosis and treatment.

Sepsis-associated acute kidney injury (SA-AKI) results in significant morbidity and mortality, and ferroptosis may play a role in its pathogenesis. Our aim was to examine the effect of exogenous H2S (GYY4137) on ferroptosis and AKI in in vivo and in vitro models of sepsis and explore the possible mechanism involved. Sepsis was induced by cecal ligation and puncture (CLP) in male C57BL/6 mice, which were randomly divided into the sham, CLP, and CLP + GYY4137 group. The indicators of SA-AKI were most prominent at 24 h after CLP, and analysis of the protein expression of ferroptosis indicators showed that ferroptosis was also exacerbated at 24 h after CLP. Moreover, the level of the endogenous H2S synthase CSE (Cystathionine-γ-lyase) and endogenous H2S significantly decreased after CLP. Treatment with GYY4137 reversed or attenuated all these changes. In the in vitro experiments, LPS was used to simulate SA-AKI in mouse renal glomerular endothelial cells (MRGECs). Measurement of ferroptosis-related markers and products of mitochondrial oxidative stress showed that GYY4137 could attenuate ferroptosis and regulate mitochondrial oxidative stress. These findings imply that GYY4137 alleviates SA-AKI by inhibiting ferroptosis triggered by excessive mitochondrial oxidative stress. Thus, GYY4137 may be an effective drug for the clinical treatment of SA-AKI.

Monthly runoff forecasting has always been a key problem in water resources management. As a data-driven method, the least square support vector machine (LSSVM) method has been investigated by numerous studies in runoff forecasting. However, selecting appropriate parameters for LSSVM is the key to obtaining satisfactory model performance. In this study, we propose a hybrid model for monthly runoff forecasting, VMD-SSA-LSSVM for short, which combines variational mode decomposition (VMD) with LSSVM and the parameters of LSSVM are optimized by a sparrow search algorithm (SSA). Firstly, VMD is utilized to decompose the original time series data into several subsequences. Secondly, LSSVM is employed to simulate each subsequence, for which the parameters are optimized by SSA. Finally, the simulated results for each subsequence are accumulated as the final results. The validity of the proposed model was verified by forecasting monthly runoff for two reservoirs located in China. Four frequently-used statistical indexes, namely the Nash efficiency coefficient, root mean squared error, correlation coefficient and mean absolute percentage error were used to evaluate model performance. The results demonstrate the superiority of VMD-SSA-LSSVM over the compared models in terms of all statistical indexes, indicating that it is beneficial for enhancing monthly runoff forecast accuracy.

Huan Xue,1,* Hao-Jie Xing,1,* Bin Wang,1 Chao Fu,1 Yu-Shan Zhang,1 Xi Qiao,1 Chao Guo,1 Xiao-Li Zhang,1 Bin Hu,1 Xin Zhao,1 Li-Jiao Deng,1 Xiao-Chan Zhu,1 Yi Zhang,1 Yun-Feng Liu2 1Department of Pharmacology, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China; 2Department of Endocrinology, First Hospital of Shanxi Medical University, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yi Zhang; Yun-Feng Liu, Tel +86-18835102847 ; +86-18703416169, Email yizhang313@163.com; nectarliu@163.comPurpose: The glucagon-like peptide-1 receptor (GLP-1R) is an effective therapeutic target for type 2 diabetes mellitus (T2DM) and non-alcoholic steatohepatitis (NASH). Research has focused on small-molecule GLP-1R agonists because of their ease of use in oral formulations and improved patient compliance. However, no small-molecule GLP-1R agonists are currently available in the market. We aimed to screen for a potential oral small-molecule GLP-1R agonist and evaluated its effect on blood glucose and NASH.Methods: The Connectivity map database was used to screen for candidate small-molecule compounds. Molecular docking was performed using SYBYL software. Rat pancreatic islets were incubated in different concentrations glucose solutions, with cinchonine or Exendin (9– 39) added to determine insulin secretion levels. C57BL/6 mice, GLP-1R−/− mice and hGLP-1R mice were used to conduct oral glucose tolerance test. In addition, we fed ob/ob mice with the GAN diet to induce the NASH model. Cinchonine (50 mg/kg or 100 mg/kg) was administered orally twice daily to the mice. Serum liver enzymes were measured using biochemical analysis. Liver tissues were examined using Hematoxylin-eosin staining, Oil Red O staining and Sirius Red staining.Results: Based on the small intestinal transcriptome of geniposide, a recognized small-molecule GLP-1R agonist, we identified that cinchonine exerted GLP-1R agonist-like effects. Cinchonine had a good binding affinity for GLP-1R. Cinchonine promoted glucose-dependent insulin secretion, which could be attenuated significantly by Exendin (9– 39), a specific GLP-1R antagonist. Moreover, cinchonine could reduce blood glucose in C57BL/6 and hGLP-1R mice, an effect that could be inhibited with GLP-1R knockout. In addition, cinchonine reduced body weight gain and food intake in ob/ob-GAN NASH mice dose-dependently. 100 mg/kg cinchonine significantly improved liver function by reducing the ALT, ALP and LDH levels. Importantly, 100 mg/kg cinchonine ameliorated hepatic steatosis and fibrosis in NASH mice.Conclusion: Cinchonine, a potential oral small-molecule GLP-1R agonist, could reduce blood glucose and ameliorate NASH, providing a strategy for developing small-molecule GLP-1R agonists.Graphical Abstract: Keywords: glucagon-like peptide-1 receptor, cinchonine, drug repurposing, non-alcoholic steatohepatitis, type 2 diabetes mellitus

One of the most prevalent malignant tumors of the digestive tract is gastric cancer (GC). Age, high salt intake, Helicobacter pylori (H. pylori) infection, and a diet deficient in fruits and vegetables are risk factors for the illness. A significant risk factor for gastric cancer is infection with H. pylori. Infecting gastric epithelial cells with virulence agents secreted by H. pylori can cause methylation of tumor genes or carcinogenic signaling pathways to be activated. Regulate downstream genes’ aberrant expression, albeit the precise mechanism by which this happens is unclear. Oncogene, oncosuppressor, and other gene modifications, as well as a number of different gene change types, are all directly associated to the carcinogenesis of gastric cancer. In this review, we describe comprehensive H. pylori and its virulence factors, as well as the activation of the NF-κB, MAPK, JAK/STAT signaling pathways, and DNA methylation following infection with host cells via virulence factors, resulting in abnormal gene expression. As a result, host-related proteins are regulated, and gastric cancer progression is influenced. This review provides insight into the H. pylori infection, summarizes a series of relevant papers, discusses the complex signaling pathways underlying molecular mechanisms, and proposes new approach to immunotherapy of this important disease.

The assessment of heavy metal pollution is crucial for water conservation. This study determined the contents of heavy metals (Cd, Cr, Cu, Ni, Pb, Zn and As) from 39 soil samples surrounding a reservoir, and analyzed the corresponding source and enrichment using enrichment factors and partial least-squares regression. The concentration of Cr (54.06 mg/kg) was lower than the background value of the reservoir area, while the Cd concentration was higher (0.96 mg/kg). Moreover, Cd, Cr, Ni, Pb, Zn and As concentrations in the south exceeded those of the northeast in the Nanwan lake reservoir (NLR). Cd and As were the dominant contaminated elements in the NLR. The Cd enrichment factor value was 11.25, areas with moderate and higher levels of pollution of Cd occupied 89.0% of the total area, while As occupied 18.4%. The dominant sources of Zn, Ni, Cu, Pb and Cr were identified as natural inputs, those of As were agricultural production activities, and those of Cd were industrial production activities. This study provides insight into the heavy metal pollution and key factors of land-use types in watersheds with tea trees as the dominant vegetation cover, and aids in the planning of water pollution prevention and ecological protection.

The taxonomic status of Knodu in the family Characidae is not yet clear. This study aimed to address this by sequencing and annotating Knodu borki Zarske, 2008.K. borki Zarske, 2008 was sequenced using a Hiseq platform and the complete mitogenome was assembled in SPAdes v3.15.2 and SOAPdenovo2 v.2.01. The mitogenome of K. borki from Guangzhou, the first sequenced species of the genus Knodu, is 16,837 bp in length and contains 13 protein-coding genes (PCGs), two ribosomal (r) RNAs, 22 transfer (t) RNAs, and one D-loop. Among these 37 genes, 28 are encoded by the heavy strand, while nine are encoded by the light strand. Twenty-one of the tRNAs can form typical cloverleaf secondary structures, except tRNA-Ser1, which lacks dihydrouridine arms. All PCGs have the same start codon (ATG), with the exception of COI (GTG). Four PCGs (ND1, ATP8, ND4L, and ND5) have TAA as the stop codon, ND6 has TAG as the stop codon, COI has AGG as the stop codon, and the remaining seven genes have incomplete stop codons of TA-/T-(ND2, COII, COIII, ND3, ND4, and Cyt b as T-, ATP6 as TA-). Phylogenetic analysis showed that K. borki belongs to the family Characidae.Our findings demonstrate that K. borki belongs to the family Characidae, due to consistency with the morphological identification. This study provides molecular information for further research on the phylogeny of the genus Knodus and for analyses of the taxonomic status of Characidae.

An UV photodetector with a vertical-structure architecture shows a fast response time of 7.76 μs and a high on/off ratio of over 5 × 103, as well as a weak-light detecting ability with a specific detectivity of 7.08 × 1011 Jones.

Interlayer ion-exchange and space confinement nature of layered titanate ensured successful transition to CuxO/mesoporous TiO2 photocatalysts of superior HER performance.

The infinite availability of solar energy grants the potential of fulfilling the energy demands and environmental sustainability requirements with more feasible and reliant renewable energy forms through photocatalysis. In the past decade, the intensive plasmonic effect, suitable work function, superior electrical conductivity and physiochemical properties have made Ag-based photocatalysts attractive components for emerging applications. The local surface plasmon resonance effect (LSPR) provides extra hot-carriers to participate in the photocatalytic process, and Schottky/Ohmic contacts would facilitate charge transfer. Here, recent studies focused on Ag-based photocatalysts for emerging applications are reviewed. Notably, the mechanisms of LSPR, the Schottky barrier and ohmic contacts are introduced together with urgent issues in CO

Well-crystallized CsSnI3thin films can be easily obtained through two-step thermal annealing at low temperatures of 40 °C and 70 °C.

Acute promyelocytic leukemia (APL) is a special type of acute myeloid leukemia (AML), accounting for about 5% to 10% of children with AML. At the genetic level, APL is featured by a unique chromosome translocation t(15;17) which results in the PML-RARA gene fusion. Most patients can be diagnosed by traditional karyotype analysis, Fluorescence-In-Situ Hybridization (FISH), or Reverse Transcription-Polymerase Chain Reaction (RT-PCR). We report the case of a child with acute promyelocytic leukemia (APL) who had characteristic chromosome translocation t(15;17) and rare PML-RARA gene mutation. This patient had an excellent response to chemotherapy, suggesting that this mutation will not affect the treatment and prognosis of APL.

This study was to optimize the exercise preconditioning (EP) intensity in protecting from exhaustive exercise-induced cardiac injury (EECI). A total of 98 male Sprague-Dawley rats were divided into 7 groups (n ​= ​14): the control group (C), the exhaustive exercise group (EE) and the EP ​+ ​EE groups, which include the V10 (53.0%̇O2max), V15 (58.4%̇O2max), V20 (67.0%̇O2max), V26 (74.0%̇O2max) and V30 (80.0%̇O2max) groups. Except the C group, the other groups were subjected to treadmill running. The serum contents of N terminal pro B type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTn-I) were detected by the enzyme-linked immunosorbent assay method, ECG was recorded, heart function was detected by pressure volume catheter and the activities of mitochondrial electron transfer pathway (ET pathway) complexes I, Ⅱ and IV were measured by high-resolution respiration instrument. Compared to the EE group, the EP groups have shown decrease of NT-proBNP and cTn-I, improvement of mitochondrial respiratory function and cardiac function. Compared to other EP groups, the V26 group has shown significant decrease of myocardial enzymes and improvement of mitochondrial function. The correlation analysis showed the EP effect was proportional to EP intensity in the range of 53.0%̇O2max-74.0%̇O2max. High intensity and long duration of exhaustive exercise caused cardiac injury and EP could decrease serum level of NT-proBNP and cTn-I, improve electrical derangement and the left ventricular function, and raise the activities of ET pathway complexes I, Ⅱ and IV. The protection of EP on EECI was improved as the EP intensity was increased from 53.0%̇O2max to 74.0%̇O2max and when EP intensity was 74.0%̇O2max, the effect was the most obvious among all the setting EP groups.

To analyze the clinical manifestations, pathological characteristics, therapeutic effect and prognosis of diffuse large B-cell lymphoma (DLBCL) transformed from follicular lymphoma (FL).A total of 45 inpatients were eligible for criteria of histologic transformation from FL to DLBCL from January 2010 to January 2021, and their clinical characteristics, diagnosis, treatment and efficacy were collected and analyzed retrospectively.Among the 45 patients, transformation occurred at diagnosis in 27 cases, during " watch and wait " phase in 7 cases and after treatment of FL in 11 cases. The median age was 56 years old (ranged from 27 to 76 years), with 23 male and 22 female. The transformations were observed in 8 cases with low-grade and 37 cases with high-grade FL. Extranodal involvement was present in 26 cases, including bone marrow infiltration in 16 cases. There were 17 cases with anemia and 32 cases met the GELF criteria of high tumor burden. B symptoms were present in 12 cases. There were 38 cases with Ki-67≥50%. The germinal center B-cell-like (GCB) subtype of DLBCL was observed in 43 cases. Efficacy was evaluated in 45 cases. The OR, CR and PR rate were 80.0%, 60.0% and 20.0%, respectively. The OR,CR rate of patients received R-CHOP was higher than those of patients received other regimens (86.11% vs 55.55%,The OR and CR rates are higher in early transformation group of patients with DLBCL transformed from FL. Patients with anemia, B symptoms, POD24, and high-risk score have poor prognosis. IPI score is the independent prognosis factor for OS.滤泡性淋巴瘤转化的弥漫大B细胞淋巴瘤患者临床特征分析.分析滤泡淋巴瘤（FL）转化的弥漫大B细胞淋巴瘤（DLBCL）患者的临床表现、病理、疗效及预后的特点.选择并回顾性分析2010年1月至2021年1月符合条件的45例FL转化为DLBCL的患者，总结其临床特点、诊断、治疗方法和疗效.45例患者中，诊断时即发生转化的27例，选择观察等待之后发生转化的7例，FL治疗后发生转化的11例；男23例，女22例；中位年龄56(27-76)岁。低级别转化8例，高级别转化37例，26例出现结外侵犯，骨髓累及16例，贫血17例，高肿瘤负荷（GELF标准）32例, 伴B症状12例，Ki-67≥50%患者38例。43例转化为GCB型DLBCL。45例患者可评价疗效，所有患者初始化疗疗效评估总有效率（ORR）为80.0%，完全缓解（CR）率为60.0%，部分缓解（PR）率20%；R-CHOP和其他方案组患者ORR分别是86.11%和55.55%（FL转化为DLBCL患者诊断时即转化组ORR及CR率高；患者贫血及B症状、POD24及高危组预后差；IPI评分是影响OS的独立预后因素.

Purpose: Incidence of contrast induced nephropathy (CIN) and related risk factors in patients with liver cancer and chronic kidney disease after trans-catheter arterial chemoembolization (TACE) is higher. The purpose of this study was to investigate the feasibility and safety of TACE therapy in such patients. Methods: A retrospective analysis was performed on 103 patients with liver cancer and chronic kidney disease who underwent TACE treatments. TACE was performed according to Seldinger’s technique of arterial embolization with minor modifications. Based on CIN diagnostic criteria, patients were divided into non-CIN (n=89) and CIN (n=14) groups. Multiple clinical parameters were assessed for the two groups after TACE. Serum creatinine levels were measured 48-72 h after TACE. Results: Tumor size (>5 cm), TACE frequency, contrast agent dosage, solitary kidney, volume of iodized oil used in the TACE (ml) and urea levels were significantly higher in CIN group in comparison with the non-CIN group, while serum albumin and haemoglobin levels were significantly lower. Multivariate logistic regression analysis confirmed that the volume of iodized oil and TACE frequency were significantly positively correlated, and serum albumin level was negatively correlated in the CIN group. Conclusion: Volume of iodized oil, TACE frequency and low serum albumin levels were found to be independent risk factors for CIN after TACE. Thus, it is safe and feasible for hepatocellular carcinoma patients with chronic kidney disease to receive TACE treatment, but adverse events management after TACE needs to be addressed.

AIM: To investigate whether circular RNA(circRNA)circ_0000144 targets microRNA(miRNA)-502-5p to regulate the proliferation, apoptosis, migration and invasion of human retinoblastoma Y79 cells. METHODS: Y79 cells were divided into si-NC group(transfected with si-NC), si-circ_0000144 group(transfected with si-circ_0000144), miR-NC group(transfected with miR-NC), miR-502-5p group(transfected with miR-502-5p mimic), pcDNA group(transfected with pcDNA), pcDNA-circ_0000144 group(transfected with pcDNA-circ_0000144), si-circ_0000144+anti-miR-NC group(transfected with si-circ_0000144+anti-miR-NC), si-circ_0000144+anti-miR-502-5p group(transfected with si-circ_0000144+anti-miR-502-5p). Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect the expression of circ_0000144 and miR-502-5p in retinoblastoma tissues and cells, thiazole blue tetrazolium bromide(MTT)detected cell proliferation, and western blot was employed to determine the expression of nuclear associated antigen Ki67(Ki-67), B cell lymphoma/lewkmia-2(Bcl-2), Bcl-2 associated X protein(Bax), matrix metalloprotease(MMP)-2, MMP-9 protein. Flow cytometry detected cell apoptosis, and Transwell measured cell migration and invasion. Bioinformatics prediction and dual luciferase report experiment analyzed whether circ_0000144 targets miR-502-5p. RESULTS: The expression of circ_0000144 in 31 cases of retinoblastoma tissue was higher than that of adjacent tissues, and the expression of miR-502-5p was lower than that of adjacent tissues(P