KIF20B Correlates with LUAD Progression and Is an Independent Risk Factor.

OBJECTIVE: Kinesin family proteins (KIFs) play crucial roles in human tumorigenesis and progression. This study aimed to investigate the expression and association of Kinesin family member 20B (KIF20B) with lung adenocarcinoma (LUAD). METHODS: RNA-seq data from LUAD patients (n = 535) were extracted from TCGA. KIF20B expression was compared between tumor tissues and controls, and between different stages of the disease. Survival and Cox regression analyses were performed, as well as in vitro cellular experiments on A549 cells. RESULTS: KIF20B is upregulated in LUAD tumor tissues compared with controls and is higher in advanced stages. Patients with high expression of KIF20B have shorter survival times. KIF20B is an independent risk factor for the prognosis of LUAD. High KIF20B expression samples were enriched in signaling pathways related to tumor progression. si-KIF20B transfection reduced migration and invasion of A549 cells and increased apoptosis. The expression of p53 and Bax proteins was upregulated by si-KIF20B, while Bcl-2 was down-regulated. DISCUSSION: This study reveals that high KIF20B expression is an independent risk factor for the poor prognosis of LUAD. The inhibition of KIF20B might be of great value for suppressing LUAD progression.

Palmitoylation of the envelope membrane proteins GP5 and M of porcine reproductive and respiratory syndrome virus is essential for virus growth.

Porcine reproductive and respiratory syndrome virus (PRRSV), an enveloped positive-strand RNA virus in the Arteiviridae family, is a major pathogen affecting pigs worldwide. The membrane (glyco)proteins GP5 and M form a disulfide-linked dimer, which is a major component of virions. GP5/M are required for virus budding, which occurs at membranes of the exocytic pathway. Both GP5 and M feature a short ectodomain, three transmembrane regions, and a long cytoplasmic tail, which contains three and two conserved cysteines, respectively, in close proximity to the transmembrane span. We report here that GP5 and M of PRRSV-1 and -2 strains are palmitoylated at the cysteines, regardless of whether the proteins are expressed individually or in PRRSV-infected cells. To completely prevent S-acylation, all cysteines in GP5 and M have to be exchanged. If individual cysteines in GP5 or M were substituted, palmitoylation was reduced, and some cysteines proved more important for efficient palmitoylation than others. Neither infectious virus nor genome-containing particles could be rescued if all three cysteines present in GP5 or both present in M were replaced in a PRRSV-2 strain, indicating that acylation is essential for virus growth. Viruses lacking one or two acylation sites in M or GP5 could be rescued but grew to significantly lower titers. GP5 and M lacking acylation sites form dimers and GP5 acquires Endo-H resistant carbohydrates in the Golgi apparatus suggesting that trafficking of the membrane proteins to budding sites is not disturbed. Likewise, GP5 lacking two acylation sites is efficiently incorporated into virus particles and these viruses exhibit no reduction in cell entry. We speculate that multiple fatty acids attached to GP5 and M in the endoplasmic reticulum are required for clustering of GP5/M dimers at Golgi membranes and constitute an essential prerequisite for virus assembly.

First report and genetic diversity of porcine bufavirus in China.

BACKGROUND: Bufavirus is a newly discovered zoonotic virus reported in numerous mammals and humans. However, the epidemiological and genetic characteristics of porcine bufaviruses (PBuVs) in China remain unclear. METHODS: To detect PBuVs in China, 384 samples (92 fecal and 292 serum specimens) were collected from 2017 to 2018, covering six provinces in China, and were evaluated by nested PCR. Further, the positive samples from different provinces were selected to obtain the complete genome of Chinese PBuVs. RESULTS: The prevalence rate of PBuV was 16.7% in Chinese domestic pigs in the Guangdong, Guangxi, Fujian, Jiangxi, Anhui, and Henan provinces. Additionally, the positive rate of fecal specimens was higher than that of the serum samples. Next, we sequenced nine near-complete genomes of Chinese field PBuV strains from different provinces. Homology and phylogenetic analyses indicated that Chinese PBuVs have high genetic variation (93.3-99.2%), showed higher nucleotide identity with an Austrian PBuV strain (KU867071.1), and developed into different branches within the same cluster. CONCLUSION: To our knowledge, this is the first report on PBuV in China, expanding the geographic boundaries of PBuV circulation. Our data demonstrate that PBuVs are widely distributed in the six Chinese provinces. Moreover, these Chinese PBuVs exhibit genetic variation and continuous evolution characteristics. Taken together, our findings provide a foundation for future studies on bufaviruses.

Population-based study of environmental/occupational lead exposure and amyotrophic lateral sclerosis: a systematic review and meta-analysis.

Lead is a known risk factor for amyotrophic lateral sclerosis (ALS). However, the results of studies exploring the relationship between lead exposure and the occurrence of ALS are inconsistent. To clarify this issue, we conducted a systematic review and meta-analysis of relevant published articles on the relationship between lead exposure and the occurrence of ALS. We searched the PubMed, MEDLINE, Embase, and Science Direct databases for relevant publications. The quality of the articles was judged according to the Newcastle-Ottawa scale, and the meta-analysis was conducted using a random effect model. A total of 583 items were retrieved of which 11 case-control studies were selected. The ratio of maximal/minimal lead exposure yielded a pooled odds ratio (OR) of 1.46 (95% confidence interval (CI) 1.16-1.83) with moderate heterogeneity (I2 = 51.8%; p = 0.019). Subgroup and sensitivity analyses showed stable results. There was evidence of publication bias, but the recalculated OR after employing the "fill and trim" method was 1.28 (95% CI 1.02-1.63). These results indicated that environmental/occupational lead exposure was positively proportional to the risk of ALS.

Protective effect of the antioxidative peptide SS31 on ionizing radiation-induced hematopoietic system damage in mice.

Ionizing radiation (IR) causes severe damage to the hematopoietic system; thus, it is necessary to explore agents or compounds that can reduce this damage. SS31 is a mitochondria-targeted peptide that can scavenge cellular reactive oxygen species (ROS) and inhibit the production of mitochondrial ROS. Therefore, in this study, we discuss the protective effect of SS31 on IR-induced hematopoietic system damage. Our results showed that treatment with 6 mg/kg SS31 elevated the survival rate of lethally irradiated mice and increased the numbers of white blood cells, red blood cells, hemoglobin and platelets in mice exposed to 4 Gy whole-body irradiation. In addition, SS31 administration improved the number of hematopoietic stem/progenitor cells (HSPCs) and the self-renewal and reconstitution abilities of these cells in irradiated mice. The elevation of ROS levels is the main cause of IR-induced hematopoietic system damage, and SS31 can effectively reduce the ROS level in HSPCs. The above results suggest that SS31 can protect the hematopoietic system from radiation-induced damage by reducing cellular ROS levels.

Effects of microRNA-206 and its target gene IGF-1 on sevoflurane-induced activation of hippocampal astrocytes in aged rats through the PI3K/AKT/CREB signaling pathway.

The study aims to explore the effects of microRNA-206 (miR-206) targeting IGF-1 on the activation of hippocampal astrocytes in aged rats induced by sevoflurane through the PI3K/AKT/CREB signaling pathway. Wistar rats and astrocytes were divided into the normal/blank, sham/negative control (NC), sevoflurane (sevo), miR-206 mimics+sevo, miR-206 inhibitors+sevo, miR-206 NC+sevo, IGF-1 shRNA+sevo, and miR-206 inhibitors+IGF-1 shRNA+sevo groups. The Morris water maze test was exhibited to assess the cognitive functions. Glial fibrillary acidic protein (GFAP) expression was detected by immunofluorescence assay. Western blotting and RT-qPCR were used to detect the expression of miR-206, IGF-1, PI3K, AKT, CREB, pPI3K, pAKT, pCREB, cytochrome-c (Cyt-c), and caspase-3. Cell viability and apoptosis were detected by MTT assay and annexin V/PI double staining respectively. Mitochondrial transmembrane potential (MTP) were determined by flow cytometry. The IGF-1 shRNA+sevo group showed reduced miR-206 expression. Compared with the normal/blank group, the sevo, and miR-206 NC+sevo groups showed decreased miR-206 and GFAP expressions, cell viability and MTP but increased expressions of IGF-1, PI3K, AKT, CREB, pPI3K, pAKT, pCREB, Cyt-c and caspase-3, as well as cell apoptosis. Similar trends were observed in the miR-206 inhibitors+sevo group when compared with the sevo group. The study provides evidence that miR-206 alleviates the inhibition of activation of hippocampal astrocytes in aged rats induced by sevoflurane by targeting IGT-1 through suppressing the PI3K/AKT/CREB signaling pathway.

Suppression of Long Non-Coding RNA LINC00652 Restores Sevoflurane-Induced Cardioprotection Against Myocardial Ischemia-Reperfusion Injury by Targeting GLP-1R Through the cAMP/PKA Pathway in Mice.

BACKGROUND/AIMS: Long non-coding RNA (lncRNA) and glucagon-like peptide 1 receptor (GLP-1R) are crucial for heart development and for adult heart structural maintenance and function. Herein, we performed a study to explore the effect of lncRNA LINC00652 (LINC00652) on myocardial ischemia-reperfusion (I/R) injury by targeting GLP-1R through the cyclic adenosine monophosphate-protein kinase A (cAMP/PKA) pathway. METHODS: Bioinformatics software was used to screen the long-chain non-coding RNAs associated with myocardial ischemia-reperfusion and to predict target genes. The mRNA and protein levels of LINC00652, GLP-1R and CREB were detected by RT-qPCR and western blotting. In order to identify the interaction between LINC00652 and myocardial I/R injury, the cardiac function, the hemodynamic changes, the pathological changes of the myocardial tissues, the myocardial infarct size, and the apoptosis of myocardial cells of mice were measured. Meanwhile, the levels of serum IL-1ß and TNF-α were detected. RESULTS: LINC00652 was overexpressed in the myocardial cells of mice with myocardial I/R injury. GLP-1R is the target gene of LINC00652. We also determined higher levels of LINC00652 and GLP-1R in the I/R modeled mice. Additionally, si-LINC00652 decreased cardiac pathology, infarct size, apoptosis rates of myocardial cells, and levels of IL-1ß and TNF-α, and increased GLP-1R expression cardiac function, normal hemodynamic index, and the expression and phosphorylation of GLP-1R and CREB proteins. CONCLUSION: Taken together, our key findings of the present highlight LINC00652 inhibits the activation of the cAMP/PKA pathway by targeting GLP-1R to reduce the protective effect of sevoflurane on myocardial I/R injury in mice.

MicroRNA-374 Exerts Protective Effects by Inhibiting SP1 Through Activating the PI3K/Akt Pathway in Rat Models of Myocardial Ischemia-Reperfusion After Sevoflurane Preconditioning.

BACKGROUND/AIMS: Ischemic heart disease is a leading cause of death in cardiovascular diseases, and microRNAs (miRs) have been reported to be potential therapeutic targets in heart disease. Herein, this study aims to investigate the effects of microRNA (miR)-374 on myocardial ischemia-reperfusion (I/R) injury in rat models pretreated with sevoflurane by targeting SP1 through the PI3K/Akt pathway. METHODS: SD rats were grouped into sham, I/R and sevoflurane + I/R (sevoflurane preconditioning and I/R) groups. The biochemical indicators, pathological changes, positive expression of SP1 protein, and apoptosis rates were measured using biochemical detection, Evans blue-TTC staining, immunohistochemistry and TUNEL staining. RT-qPCR and Western blotting were used to investigate the expression of miR-374 mRNA and the protein expression of SP1, PI3K, HO-1, p53, iNOS, c-fos, Akt/p-Akt, and GSK-3ß/p-GSK-3ß. Cardiomyocytes were treated with miR-374 mimics, miR-374 inhibitors, or siRNA-SP1. Cardiomyocyte proliferation and cycle distribution and apoptosis were studied by MTT and flow cytometry. RESULTS: Compared with the I/R group, in the sevoflurane + I/R group, serum SOD and IL-10 increased, while MDA, LDH, CK, TNF-α, IL-6 and IL-10 decreased, as did the percentage of infarct area, the positive rate of SP1 and the apoptosis index. The expression of SP1, p53, iNOS and c-fos decreased, and the miR-374 expression of PI3K, HO-1, Akt/p-Akt, GSK-3ß/p-GSK-3ß increased. With the upregulation of miR-374 and the downregulation of SP1, the expression of SP1, p53, iNOS and c-fos decreased, as did the proportion of cells in G1 phase and the apoptosis rate; the expression of PI3K, HO-1, Akt/p-Akt, GSK-3ß/p-GSK-3ß increased. The results in the miR-374 inhibitor group contrasted with the above results. CONCLUSION: The results indicated that miR-374 could alleviate myocardial I/R damage in rat models pretreated with sevoflurane by targeting SP1 by activating the PI3K/Akt pathway.

Performance of a second-generation methylated SEPT9 test in detecting colorectal neoplasm.

BACKGROUND AND AIM: Screening and early detection reduces mortality due to colorectal cancer (CRC). Methylated Septin 9 (SEPT9) is a new blood-based biomarker for CRC. We evaluated the performance of the second-generation SEPT9 assay for the detection of colorectal neoplasm, and compared it with fecal immunochemical test (FIT). METHODS: A total of 135 patients with CRC, 169 with adenomatous polyps, 81 with hyperplastic polyps, and 91 healthy controls were included. The clinical status of all subjects was verified by colonoscopy. In all patients, peripheral blood samples were taken for SEPT9 testing using Epi proColon 2.0 test. For 177 patients, both SEPT9 and FIT were performed. RESULTS: The sensitivity and specificity of SEPT9 for CRC were 74.8% (95% confidence interval [CI]: 67.0-81.6%) and 87.4% (vs non-CRC, 95% CI: 83.5-90.6%), respectively. SEPT9 was positive in 66.7% of stage I, 82.6% of stage II, 84.1% of stage III, and 100% of stage IV CRCs. The sensitivity of SEPT9 for advanced adenomas was 27.4% (95% CI: 18.7-37.6%). The sensitivity and specificity of FIT for CRC was 58.0% (95% CI: 46.1-69.2%) and 82.4% (95% CI: 74.4-88.7%), respectively. SEPT9 showed better performance in CRC detection than FIT, but similar among advanced adenomas. CONCLUSIONS: With improved performance characteristics in detecting CRC, the second-generation SEPT9 assay could play an important role in CRC screening and early detection.

[Treatment of irreducible intertrochanteric femoral fracture in elderly by folding top technique combined with right-angle pliers prying and pulling under G-arm X-ray fluoroscopy].

Objective: To explore the effectiveness of irreducible intertrochanteric femoral fracture in the elderly by treating with folding top technique and right-angle pliers prying and pulling under G-arm X-ray fluoroscopy. Methods: The clinical data of 74 elderly patients with irreducible intertrochanteric femoral fracture admitted between February 2016 and December 2022 and met the selection criteria were retrospectively analyzed. Among them, 38 cases were treated with folding top technique combined with right-angle pliers prying and pulling under G-arm X-ray fluoroscopy and intramedullary nailing fixation (study group), and 36 cases were treated with limited open reduction combined with other reduction methods and intramedullary nailing fixation (control group). There was no significant difference in baseline data between the two groups, such as age, gender, cause of injury, affected side and classification of fractures, complicated medical diseases, and time from injury to operation ( P>0.05). The operation time, intraoperative blood loss, hospital stay, fracture reduction time, fracture healing time, and complications of the two groups were recorded and compared. The quality of fracture reduction was evaluated by Baumgaertner et al. and Chang et al. fracture reduction standards. Results: Patients in both groups were followed up 10-14 months, with an average of 12 months. The operation time and intraoperative blood loss in the study group were significantly less than those in the control group ( P<0.05), there was no significant difference in hospital stay between the two groups ( P>0.05). At 2 days after operation, according to the fracture reduction standards of Baumgaertner et al. and CHANG Shimin et al., the quality of fracture reduction in the study group was better than that in the control group, and the fracture reduction time in the study group was shorter than that in the control group, with significant differences ( P<0.05). After operation, the fractures of the two groups all healed, and there was no significant difference in healing time between the two groups ( P>0.05). During the follow-up, there was no complication such as incision infection, internal fixation failure, deep venous thrombosis of lower limbs, intramedullary nail breakage, spiral blade cutting, or hip varus in the two groups, except for 2 cases of coxa vara in the control group. Conclusion: For the irreducible intertrochanteric femoral fracture, using folding top technique combined with right-angle pliers prying and pulling under G-arm X-ray fluoroscopy can obviously shorten the operation time, reduce the intraoperative blood loss, and improve the quality of fracture reduction.

In Situ Mapping of Phase Evolutions in Rapidly Heated Zr-Based Bulk Metallic Glass with Oxygen Impurities.

Metallic glasses exhibit unique mechanical properties. For metallic glass composites (MGC), composed of dispersed nanocrystalline phases in an amorphous matrix, these properties can be enhanced or deteriorated depending on the volume fraction and size distribution of the crystalline phases. Understanding the evolution of crystalline phases during devitrification of bulk metallic glasses upon heating is key to realizing the production of these composites. Here, results are presented from a combination of in situ small- and wide-angle X-ray scattering (SAXS and WAXS) measurements during heating of Zr-based metallic glass samples at rates ranging from 102 to 104 Ks-1 with a time resolution of 4ms. By combining a detailed analysis of scattering experiments with numerical simulations, for the first time, it is shown how the amount of oxygen impurities in the samples influences the early stages of devitrification and changes the dominant nucleation mechanism from homogeneous to heterogeneous. During melting, the oxygen rich phase becomes the dominant crystalline phase whereas the main phases dissolve. The approach used in this study is well suited for investigation of rapid phase evolution during devitrification, which is important for the development of MGC.

SLC26A4-AS1 Aggravates AngII-induced Cardiac Hypertrophy by Enhancing SLC26A4 Expression. / SLC26A4-AS1 Agrava a Hipertrofia Cardíaca Induzida por AngII Aumentando a Expressão de SLC26A4.

BACKGROUND: It has been reported that solute carrier family 26 members 4 antisense RNA 1 (SLC26A4-AS1) is highly related to cardiac hypertrophy. OBJECTIVE: This research aims to investigate the role and specific mechanism of SLC26A4-AS1 in cardiac hypertrophy, providing a novel marker for cardiac hypertrophy treatment. METHODS: Angiotensin II (AngII) was infused into neonatal mouse ventricular cardiomyocytes (NMVCs) to induce cardiac hypertrophy. Gene expression was detected by quantitative real-time PCR (RT-qPCR). Protein levels were evaluated via western blot. Functional assays analyzed the role of SLC26A4-AS1. The mechanism of SLC26A4-AS1 was assessed by RNA-binding protein immunoprecipitation (RIP), RNA pull-down, and luciferase reporter assays. The P value <0.05 was identified as statistical significance. Student's t-test evaluated the two-group comparison. The difference between different groups was analyzed by one-way analysis of variance (ANOVA). RESULTS: SLC26A4-AS1 is upregulated in AngII-treated NMVCs and promotes AngII-induced cardiac hypertrophy. SLC26A4-AS1 regulates its nearby gene solute carrier family 26 members 4 (SLC26A4) via functioning as a competing endogenous RNA (ceRNA) to modulate the microRNA (miR)-301a-3p and miR-301b-3p in NMVCs. SLC26A4-AS1 promotes AngII-induced cardiac hypertrophy via upregulating SLC26A4 or sponging miR-301a-3p/miR-301b-3p. CONCLUSION: SLC26A4-AS1 aggravates AngII-induced cardiac hypertrophy via sponging miR-301a-3p or miR-301b-3p to enhance SLC26A4 expression.

FUNDAMENTO: Foi relatado que o RNA 1 antisenso 1 (SLC26A4-AS1) do membro 4 da família de transportadores de soluto 26 está altamente relacionado à hipertrofia cardíaca. OBJETIVO: Esta pesquisa visa investigar o papel e o mecanismo específicos de SLC26A4-AS1 na hipertrofia cardíaca, fornecendo um novo marcador para o tratamento da hipertrofia cardíaca. MÉTODOS: Angiotensina II (AngII) foi infundida em cardiomiócitos ventriculares (NMVCs) de camundongos neonatos para induzir hipertrofia cardíaca. A expressão gênica foi detectada por PCR quantitativo em tempo real (RT-qPCR). Os níveis de proteína foram avaliados por western blot. Ensaios funcionais analisaram o papel de SLC26A4-AS1. O mecanismo de SLC26A4-AS1 foi avaliado por imunoprecipitação de proteína de ligação a RNA (RIP), pull-down de RNA e ensaios de luciferase repórter. O valor de p < 0,05 foi identificado como significância estatística. O teste t de Student avaliou a comparação dos dois grupos. A diferença entre os diferentes grupos foi analisada por análise de variância (ANOVA) de uma via. RESULTADOS: SLC26A4-AS1 é regulado para cima em NMVCs tratados com AngII e promove hipertrofia cardíaca induzida por AngII. SLC26A4-AS1 regula o membro 4 da família de transportadores de soluto 26 (SLC26A4) por meio do funcionamento como um RNA endógeno competitivo (ceRNA) para modular o microRNA (miR)-301a-3p e o miR-301b-3p em NMVCs. SLC26A4-AS1 promove hipertrofia cardíaca induzida por AngII via regulação para cima de SLC26A4 ou absorção de miR-301a-3p/miR-301b-3p. CONCLUSÃO: SLC26A4-AS1 agrava a hipertrofia cardíaca induzida por AngII via absorção de miR-301a-3p ou miR-301b-3p para aumentar a expressão de SLC26A4.

miR-29a-3p inhibits the malignant characteristics of non-small cell lung cancer cells by reducing the activity of the Wnt/ß-catenin signaling pathway.

MicroRNAs (miRNAs) can influence non-small cell lung cancer (NSCLC) in a tumor-suppressive and oncogenic manner. The present study aimed to investigate the effects and underlying mechanisms of miR-29a-3p in NSCLC. NSCLC cell lines (A549, H1299, and H460) and a normal lung epithelial cell line (BEAS-2B) were used. Additionally, a mouse lung tumor xenograft model was established using A549 cells and used to determine the effects of miR-29a-3p on NSCLC in vivo. Tumor volumes were measured every week. The expression of miR-29a-3p in cells and lung tissues were detected by RT-qPCR. Cell proliferation was detected using Cell Counting Kit-8 and EdU assays. Migration and invasion were assessed using wound healing and Transwell invasion assays, respectively. Ki-67 expression was detected using immunohistochemical staining. The expression levels of Wnt3a and ß-catenin were determined using western blotting. miR-29a-3p expression was significantly downregulated in NSCLC cells and mice. In contrast to miR-29a-3p knockdown, miR-29a-3p overexpression decreased NSCLC cell proliferation, migration, and invasion as well as tumor growth in in the NSCLC mouse model. Moreover, miR-29a-3p overexpression decreased the protein expression levels of Wnt3a and ß-catenin. The inhibitory effects of miR-29a-3p on NSCLC cells were reversed by LiCl (an activator of the Wnt signaling pathway). In conclusion, miR-29a-3p prevented NSCLC tumor growth and cell proliferation, migration, and invasion by inhibiting the Wnt/ß-catenin signaling pathway. This finding offers novel insights into the prognosis and treatment of NSCLC.

Extracellular Vesicle-Derived miR-105-5p Promotes Malignant Phenotypes of Esophageal Squamous Cell Carcinoma by Targeting SPARCL1 via FAK/AKT Signaling Pathway.

Objective: Esophageal squamous cell carcinoma (ESCC) presents high morbidity and mortality. It was demonstrated that blood-derived vesicles can facilitate ESCC development and transmit regulating signals. However, the molecular mechanism of vesicle miRNA secreted by tumor cells affecting ESCC progression has not been explored. Methods: The mRNA-related signaling pathways and differentially expressed genes were screened out in TCGA dataset. The levels of miRNA-105-5p and SPARCL1 were determined by qRT-PCR. Protein level determination was processed using Western blot. The interaction between the two genes was verified with the dual-luciferase method. A transmission electron microscope was utilized to further identify extracellular vesicles (EVs), and co-culture assay was performed to validate the intake of EVs. In vitro experiments were conducted to evaluate cell function changes in ESCC. A mice tumor formation experiment was carried out to observe tumor growth in vivo. Results: MiRNA-105-5p expression was increased in ESCC, while SPARCL1 was less expressed. MiRNA-105-5p facilitated cell behaviors in ESCC through targeting SPARCL1 and regulating the focal adhesion kinase (FAK)/Akt signaling pathway. Blood-derived external vesicles containing miRNA-105-5p and EVs could be internalized by ESCC cells. Then, miRNA-105-5p could be transferred to ESCC cells to foster tumorigenesis as well as cell behaviors. Conclusion: EV-carried miRNA-105-5p entered ESCC cells and promoted tumor-relevant functions by mediating SPARCL1 and the FAK/Akt signaling pathway, which indicated that the treatment of ESCC via serum EVs might be a novel therapy and that miRNA-105-5p can be a molecular target for ESCC therapy.

Three-dimensional computed tomography angiography and bronchography combined with three-dimensional printing for thoracoscopic pulmonary segmentectomy in stage IA non-small cell lung cancer.

BACKGROUND: Compared with lobectomy, the anatomical structure of the lung segment is relatively complex and easy to occur variation, thus it increases the difficulty and risk of precise segmentectomy. The application of three-dimensional computed tomography bronchography and angiography (3D-CTBA) combined with a three-dimensional printing (3D printing) model can ensure the safety of operation and simplify the surgical procedure to a certain extent. We aimed to estimate the value of 3D-CTBA and 3D printing in thoracoscopic precise pulmonary segmentectomy. METHODS: We retrospectively reviewed the clinical data of 65 patients who underwent anatomical segmentectomy at the Affiliated Hospital of Shaoxing University from January 2019 to August 2020. The patients were divided into two groups: a 3D-CTBA combined with 3D printing group (30 patients) and a general group (35 patients). The perioperative data of the two groups were compared. RESULTS: Compared with the general segmentectomy group at the same period in our center, the surgery time of the group guided by 3D-CTBA and 3D printing was significantly shorter. Intraoperative blood loss in the 3D-CTBA and 3D printing group was also apparently lower than in the general group. Hospital stay and postoperative chest tube duration showed no significant differences between the two groups, and neither did postoperative complications such as pneumonia, hemoptysis, arrhythmia, and pulmonary air leakage. CONCLUSIONS: 3D-CTBA combined with 3D printing clearly identifies the precise pulmonary segmental structures, avoids intraoperative accidental injury, reduces intraoperative blood loss, shortens the operation time and improves the safety of thoracoscopic pulmonary segmentectomy in stage IA non-small cell lung cancer (NSCLC).

In situ correlation between metastable phase-transformation mechanism and kinetics in a metallic glass.

A combination of complementary high-energy X-ray diffraction, containerless solidification during electromagnetic levitation and transmission electron microscopy is used to map in situ the phase evolution in a prototype Cu-Zr-Al glass during flash-annealing imposed at a rate ranging from 102 to 103 K s-1 and during cooling from the liquid state. Such a combination of experimental techniques provides hitherto inaccessible insight into the phase-transformation mechanism and its kinetics with high temporal resolution over the entire temperature range of the existence of the supercooled liquid. On flash-annealing, most of the formed phases represent transient (metastable) states - they crystallographically conform to their equilibrium phases but the compositions, revealed by atom probe tomography, are different. It is only the B2 CuZr phase which is represented by its equilibrium composition, and its growth is facilitated by a kinetic mechanism of Al partitioning; Al-rich precipitates of less than 10 nm in a diameter are revealed. In this work, the kinetic and chemical conditions of the high propensity of the glass for the B2 phase formation are formulated, and the multi-technique approach can be applied to map phase transformations in other metallic-glass-forming systems.

Knockdown of long non-coding RNA TTTY15 protects cardiomyocytes from hypoxia-induced injury by regulating let-7b/MAPK6 axis.

Acute myocardial infarction (AMI) is a serious threat to human health. Long non-coding RNAs (lncRNAs) are known to be involved in the progression of AMI. The objective of this paper was to explore the functional effect of lncRNA testis-specific transcript Y-linked 15 (TTTY15) on hypoxia-induced cardiomyocyte injury. Human cardiomyocytes AC16 were cultured under hypoxic conditions to induce cardiomyocyte injury. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to check the expression of TTTY15, microRNA let-7b, and Mitogen-activated protein kinase 6 (MAPK6). Western blot was implemented for protein detection. Cell viability and apoptosis were examined by Cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. The target association among TTTY15, let-7b, and MAPK6 was validated by dual-luciferase reporter assay, pull-down assay and RNA immunoprecipitation (RIP) assay. We found that the abundances of TTTY15 and MAPK6 were elevated, while let-7b level declined in hypoxia-induced AC16 cells. Knockdown of TTTY15 increased cell viability, and inhibited apoptosis of hypoxia-induced AC16 cells. TTTY15 bound to and inversely regulated let-7b. Likewise, MAPK6 was a target of let-7b and was negatively regulated by let-7b. Silencing of TTTY15 ameliorated the impact of let-7b downregulation or MAPK6 upregulation on hypoxia-induced cardiomyocyte injury. TTTY15 modulated MAPK6 enrichment by sponging let-7b. In conclusion, knockdown of TTTY15 suppressed hypoxia-induced cardiomyocyte injury through the let-7b/MAPK6 axis.

SEPT9 Gene Methylation as a Noninvasive Marker for Hepatocellular Carcinoma.

BACKGROUND: Early detection appears to be the most effective approach to improve the overall survival of patients with hepatocellular carcinoma (HCC). We evaluated the potential performance of plasma SEPT9 methylation (mSEPT9) as a noninvasive biomarker for the diagnosis of patients with HCC. METHODS: A total of 373 subjects were included, and the group consisted of 104 HCC patients, 95 with an at-risk disease, and 174 healthy controls (HC). The methylation of mSEPT9 was determined using methylation-specific fluorescence quantitative PCR. The diagnostic performance of plasma mSEPT9 for HCC was assessed in a single-blind manner. RESULTS: The receiver operating characteristic (ROC) curve showed that plasma mSEPT9 can be used to detect and discriminate HCC with an area under the ROC curve (AUROC) of 0.961, a sensitivity of 82.7%, and specificity of 96.0% from HC. These results showed that plasma mSEPT9 had better diagnostic performance than serum alpha fetoprotein (AFP) (AUROC 0.881, sensitivity 57.7%, and specificity 98.3%). Similar results were noted in the detection of early-stage HCC. When combined with serum AFP, the sensitivity increased to 91.3% and 87.7% for the detection of HCC and early-stage HCC,respectively. Notably, the levels of plasma mSEPT9 dramatically decreased after surgery (P = 0.001). CONCLUSIONS: Plasma SEPT9 methylation might serve as a useful and noninvasive biomarker for the diagnosis of HCC and can be used to evaluate the therapeutic efficacy of HCC treatment.

Fast-current-heating devices to study in situ phase formation in metallic glasses by using high-energy synchrotron radiation.

Details of fast-resistive-heating setups, controlled heating ranging from ∼101 K s-1 to ∼103 K s-1, to study in situ phase transformations (on heating and on cooling) in metallic glasses by high-energy synchrotron x-ray diffraction are discussed. Both setups were designed and custom built at the Leibniz Institute for Solid State and Materials Research Dresden (IFW Dresden) and have been implemented at the P02.1 Powder Diffraction and Total Scattering Beamline and the P21.1 Swedish Materials Science Beamline at PETRA III storage ring, DESY, Hamburg. The devices are interchangeable at both beamlines. Joule heating is triggered automatically and is timed with the incident beam and detector. The crystallization process can be controlled via a feedback circuit by monitoring the change in the time-dependent resistivity and temperature of glasses. Different ambient atmospheres, such as vacuum and inert gases (He and Ar), can be used to control oxidation and cooling. The main focus of these devices is on understanding the crystallization mechanism and kinetics in metallic glasses, which are brittle and for which fast heating gives defined glass-crystal composites with enhanced plasticity. As an example, phase-transformation sequence(s) in a prototyped Cu-Zr-based metallic glass is described on heating, and a crystalline phase beneficial to the plasticity is identified.

The protective effect of propofol on ionizing radiation-induced hematopoietic system damage in mice.

The hematopoietic system is highly sensitive to ionizing radiation (IR), and IR can cause injury to hematopoietic stem cells (HSCs); the main reason for this may be elevated reactive oxygen species (ROS) levels. Propofol is an anesthetic drug commonly used in clinical practice. The chemical structure of propofol is similar to that of vitamin E, and propofol has an antioxidant capacity. Therefore, in this work the effect of using propofol to protect against IR-induced hematopoietic system injury is evaluated. The data suggested that when the irradiated mice were treated with 20 mg kg-1 of propofol, the survival rate of lethally irradiated mice increased significantly, furthermore, the radiation-induced decrease of white blood cells (WBCs), red blood cells (RBCs), hemoglobin (HGC) and platelets (PLT) in peripheral blood is improved significantly. In addition, propofol could also increase the irradiated HSC and hematopoietic progenitor cell (HPC) frequencies, improving the self-renewal and differentiation abilities of HSCs and HPCs in irradiated mice. Next the ROS levels in HSCs and HPCs were measured, and the results showed that propofol could effectively decrease the ROS levels in these cells. The underlying ROS-scavenging mechanisms are further explored, and the results show that the Nrf2 pathway plays an important role in propofol's radiation protective effects, however, propofol can also increase the proliferation of the Nrf2 inhibitor-treated Lineage- cells after exposure to 4 Gy radiation. The data suggest that propofol has a radio-protective effect against IR-induced hematopoietic system damage through reducing cellular ROS in HSCs and HPCs partly through the Nrf2 pathway.