The efficacy and safety of ultrasonic bone scalpel for removing retrovertebral osteophytes in anterior cervical discectomy and fusion: A retrospective study.

In this study, we present a novel surgical method that utilizes the ultrasonic bone scalpel (UBS) for the removal of large retrovertebral osteophytes in anterior cervical discectomy and fusion (ACDF) and evaluate its safety and efficacy in comparison to the traditional approach of using high-speed drill (HSD). A total of 56 patients who underwent ACDF for retrovertebral osteophytes were selected. We recorded patients' baseline information, operation time, intraoperative blood loss, complications, JOA and VAS scores, and other relevant data. The mean operation time and the mean intraoperative blood loss in the UBS group were less than those in the HSD group (P < 0.05). Although both groups exhibited considerable improvements in JOA and VAS scores following surgery, there was no statistically significant difference between the two groups (P > 0.05). Additionally, no significant disparities were found in bone graft fusion between the two groups at 6- and 12-months postsurgery. Notably, neither group exhibited complications such as dura tear or spinal cord injury. Our study found that the use of UBS reduced operative time, minimized surgical bleeding, and led to clinical outcomes comparable to HSD in ACDF. This technique offers an effective and safe method of removing large retrovertebral osteophytes.

Genetic diversity and phylogenetic relationship estimation of Shanxi indigenous goat breeds using microsatellite markers.

The objective of this study was to assess the genetic diversity, phylogenetic relationship and population structure of five goat breeds in Shanxi, China. High genetic diversities were found in the five populations, among which, Licheng big green goat (LCBG) has the highest genetic diversity, while Jinlan cashmere goat (JLCG) population has the lowest genetic diversity. Bottleneck analysis showed the absence of recent genetic bottlenecks in the five goat populations. Genetic differentiation analysis shows that the closest genetic relationship between LCBG and LLBG (Lvliang black goat) was found, and the genetic distance between JLCG and the other four populations is the largest. The population structure of JLCG is different from the other four populations with K = 2, while LCBG and LLBG have high similarity population structure as the K value changes. Knowledge about genetic diversity and population structure of indigenous goats is essential for genetic improvement, understanding of environmental adaptation as well as utilization and conservation of goat breeds.

Monitoring of gastrointestinal carcinoma via molecular residual disease with circulating tumor DNA using a tumor-informed assay.

BACKGROUND: Circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) detection, which can identify disease relapse ahead of radiological imaging, has shown promising performance. The objective of this study was to develop and validate OriMIRACLE S (Minimal Residual Circulating Nucleic Acid Longitudinal Detection in Solid Tumor), a highly sensitive and specific tumor-informed assay for MRD detection. METHODS: Tumor-specific somatic single nucleotide variants (SNVs) were identified via whole exome sequencing of tumor tissue and matched germline DNA. Clonal SNVs were selected using the OriSelector algorithm for patient-specific, multiplex PCR-based NGS assays in MRD detection. Plasma-free DNA from patients with gastrointestinal tumors prior to and following an operation, and during monitoring, were ultradeep sequenced. RESULTS: The detection of three positive sites was sufficient to achieve nearly 100% overall sample level sensitivity and specificity and was determined by calculating binomial probability based on customized panels containing 21 to 30 variants. A total of 127 patients with gastrointestinal tumors were enrolled in our study. Preoperatively, MRD was positive in 18 of 26 patients (69.23%). Following surgery, MRD was positive in 24 of 82 patients (29.27%). The positivity rate for MRD was 33.33% (n = 18) for gastric adenocarcinoma and 32.26% (n = 62) for colorectal cancer. Twenty (20) of 59 patients (34.48%) experienced a change in MRD status over the monitoring period. Patients 8 and 31 responded to 3 cycles of systemic therapy, after which levels for all ctDNA dropped below the detection limit. Patient 53 was an example of using MRD to predict tumor metastasis. Patient 55 showed a weak response to treatments first and respond to new systemic therapy after tumor progression. CONCLUSION: Our study identified a sensitive and specific clinical detection method for low frequency ctDNA, and explored the detection performance of this technology in gastrointestinal tumors.

Molecular genetics and quantitative traits divergence among populations of Eothenomys miletus from Hengduan Mountain region.

An important objective of evolutionary biology has always been to grasp the evolutionary and genetic processes that contribute to speciation. The present work provides the first detailed account of the genetic and physiological adaptation to changing environmental temperatures as well as the reasons causing intraspecific divergence in the Eothenomys miletus from the Hengduan Mountain (HM) region, one of the biodiversity hotspots. One hundred sixty-one E. miletus individuals from five populations in the HM region had their reduced-representation genome sequenced, and one additional individual from each community had their genomes resequenced. We then characterized the genetic diversity and population structure of each population and compared the phenotypic divergence in traits using neutral molecular markers. We detected significant phenotypic and genetic alterations in E. miletus from the HM region that were related to naturally occurring diverse habitats by combining morphometrics and genomic techniques. There was asymmetric gene flow among the E. miletus populations, indicating that five E. miletus populations exhibit an isolation-by-island model, and this was supported by the correlation between F ST and geographic distance. Finally, P ST estimated by phenotypic measures of most wild traits were higher than differentiation at neutral molecular markers, indicating directional natural selection favoring different phenotypes in different populations must have been involved to achieve this much differentiation. Our findings give information on the demographic history of E. miletus, new insights into their evolution and adaptability, and literature for studies of a similar nature on other wild small mammals from the HM region.

Effects of exogenous melatonin on body mass and thermogenesis in red-backed vole (Eothenomys miletus) between Kunming and Dali regions.

Melatonin (MEL) is an indole hormone synthesized and secreted by the pineal gland at night, which is involved in the regulation of body mass and thermogenesis in small mammals. To test the effects of exogenous MEL on body mass and thermogenic ability in two different red-backed vole (Eothenomys miletus) populations from two different regions (Kunming [KM] and Dali [DL]) with different annual variation in climatic variables, such as temperature, sunshine and rainfall. we traced the changes of energy balance in E. miletus from KM and DL, which were placed at 25 ± 1°C with photoperiod of 12 L:12 D, intraperitoneal injection of MEL was performed daily for 28 days. The results showed that body mass and food intake were significantly decreased, while resting metabolic rate (RMR) and nonshivering thermogenesis (NST) were significantly increased after MEL injection; Contents of total protein, mitochondrial protein, the activities of cytochrome C oxidase (COX) and α-glycerophosphate oxidase (α-PGO) in liver and brown adipose tissue (BAT) were enhanced; the activity of thyroxin 5'-deiodinase (T4 5'-DII) and uncoupling protein 1 (UCP1) in BAT were also increased. Serum leptin, triiodothyronine (T3 ) levels and T3 /T4 ratio were significantly increased, thyroxine (T4 ) levels was significantly decreased. Moreover, body mass and food intake in E. miletus from KM were higher than those from DL, but RMR and NST were lower than those from DL. Changes of body mass, food intake and thermogenic activity of KM were higher than those of DL when exposed to injection of MEL, indicating that E. miletus in KM were more sensitive to MEL. Furthermore, MEL was involved in the regulation of body mass and thermogenesis in E. miletus between KM and DL.

Population genomics provides insights into the evolution and adaptation of tree shrews (Tupaia belangeri) in China.

Physiological adaptation of tree shrews (Tupaia belangeri) to changing environmental temperature has been reported in detail. However, the T. belangeri origin (mainland or island), population history, and adaptation to historical climate change remain largely unknown or controversial. Here, for the first time, we sequenced the simplified genome of 134 T. belangeri individuals from 12 populations in China and further resequenced one individual from each population. Using population genomic approaches, we first observed considerable genetic variation in T. belangeri. Moreover, T. belangeri populations formed obvious genetic structure and reflected different demographic histories; they generally exhibited high genetic diversity, although the isolated populations had relatively low genetic diversity. The results presented in this study indicate that T. b. modesta and T. b. tonquinia were separated recently and with a similar population dynamics. Second, physical barriers rather than distance were the driving factors of divergence, and environmental heterogeneity may play an important role in genetic differentiation in T. belangeri. Moreover, our analyses highlight the role of historical global climates in the T. belangeri population dynamics and indicate that the decrease of the T. belangeri population size may be due to the low temperature. Finally, we identified the olfaction-associated adaptive genes between different altitude populations and found that olfactory-related genes of high-altitude populations were selectively eliminated. Our study provides demographic history knowledge of T. belangeri; their adaption history offers new insights into their evolution and adaptation, and provides valuable baseline information for conservation measures.

Roles of Ghrelin and Leptin in Body Mass Regulation under Food Restriction Based on the AMPK Pathway in the Red-Backed Vole, Eothenomys miletus, from Kunming and Dali Regions.

The phenotype plasticity of animals' physiological characteristics is an important survival strategy to cope with environmental changes, especially the change in climate factors. Small mammals that inhabit seasonally changing environments often face the stress of food shortage in winter. This study measured and compared the thermogenic characteristics and related physiological indicators in the adenosine-5'-monophosphate-activated protein kinase (AMPK) pathway in Eothenomys miletus between Kunming (KM, n = 18) and Dali (DL, n = 18) under food restriction and refeeding. The results showed that food restriction and the region have significant effects on body mass, the resting metabolic rate (RMR), hypothalamic neuropeptide gene expression, ghrelin levels in the stomach and serum, serum leptin level and the activity of AMPK, and malonyl CoA and carnitine palmitoyltransferase 1 (CPT-1) activity. Food restriction reduced the body mass, the gene expression of neuropeptide proopiomelanocortin (POMC), cocaine- and amphetamine-regulated transcription peptide (CART), and leptin level. However, the ghrelin concentration and AMPK activity increased. After refeeding, there was no difference in these physiological indexes between the food restriction and control groups. Moreover, the physiological indicators also showed regional differences, such as the body mass, POMC and CART gene expression, ghrelin concentration in the stomach and serum, and AMPK activity in DL changed more significantly. All these results showed that food restriction reduces energy metabolism in E. miletus. After refeeding, most of the relevant physiological indicators can return to the control level, indicating that E. miletus has strong phenotypic plasticity. Ghrelin, leptin, and the AMPK pathway play an important role in the energy metabolism of E. miletus under food restriction. Moreover, regional differences in physiological indicators under food restriction may be related to the different temperatures or food resources in different regions.

Protein-protein interactions between RUNX3 and ZEB1 in chronic lung injury induced by methamphetamine abuse.

Methamphetamine (MA) is the most common and highly addictive substance abuse drug. Runt-related transcription factor 3 (RUNX3) and Zinc finger E-box-binding homeobox 1 (ZEB1) are associated with lung inflammation and fibrosis. However, the protein-protein interactions (PPIs) between RUNX3 and ZEB1 and its involvement in MA-induced chronic lung injury is still unclear. In this study, we evaluated lung injury using echocardiography, hematoxylin and eosin staining, and western blot analysis. The viability of alveolar epithelial cells (AECs) was assessed using cell counting kit-8. Molecular Operating Environment software, Search Tool for the Retrieval of Interacting Genes/Proteins database, co-immunoprecipitation, assay and confocal immunofluorescence assay were used to predict and identify the PPIs between RUNX3 and ZEB1. The expression of RUNX3 and ZEB1 were knockdown in AECs using siRNA. The results revealed that MA exposure increased the peak blood flow velocity of the pulmonary artery and the acceleration time of pulmonary artery blood flow. Further, exposure to MA also causes adhesion and fusion of the alveolar walls and altered AEC activity. A decrease in the expression of RUNX3 and an increase in the expression of ZEB1 and its downstream signaling molecules were observed on MA exposure. The PPIs between RUNX3 and ZEB1 were identified. Further, an increase in the protein binding rate of RUNX3-ZEB1 was observed in MA-induced lung injury. These results show interactions between RUNX3 and ZEB1. RUNX3 protects against lung injury; however, ZEB1 expression and the PPIs between ZEB1 and RUNX3 has deleterious effects on chronic lung injury induced by MA exposure. Our results provide a new therapeutic approach for the treatment of chronic lung injury due to MA exposure.

Differences of energy adaptation strategies in Tupaia belangeri between Pianma and Tengchong region by metabolomics of liver: Role of warmer temperature.

Global warming is becoming the future climate trend and will have a significant impact on small mammals, and they will also adapt at the physiological levels in response to climate change, among which the adaptation of energetics is the key to their survival. In order to investigate the physiological adaptation strategies in Tupaia belangeri affected by the climate change and to predict their possible fate under future global warming, we designed a metabonomic study in T. belangeri between two different places, including Pianma (PM, annual average temperature 15.01°C) and Tengchong (TC, annual average temperature 20.32°C), to analyze the differences of liver metabolite. Moreover, the changes of resting metabolic rate, body temperature, uncoupling protein 1content (UCP1) and other energy indicators in T. belangeri between the two places were also measured. The results showed that T. belangeri in warm areas (TC) reduced the concentrations of energy metabolites in the liver, such as pyruvic acid, fructose 6-phosphate, citric acid, malic acid, fumaric acid etc., so their energy metabolism intensity was also reduced, indicating that important energy metabolism pathway of glycolysis and tricarboxylic acid cycle (TCA) pathway reduced in T. belangeri from warmer habitat. Furthermore, brown adipose tissue (BAT) mass, UCP1 content and RMR in TC also decreased significantly, but their body temperature increased. All of the results suggested that T. belangeri adapt to the impact of warm temperature by reducing energy expenditure and increasing body temperature. In conclusion, our research had broadened our understanding of the physiological adaptation strategies to cope with climate change, and also provided a preliminary insight into the fate of T. belangeri for the future global warming climate.

Comparative research of intestinal microbiota diversity and body mass regulation in Eothenomys miletus from different areas of Hengduan mountain regions.

In order to investigate the effects of different areas on intestinal bacterial diversity and body mass regulation in Eothenomys miletus from Hengduan mountain regions, and to explore the community structure and diversity of intestinal microflora and their role in body mass regulation. E. miletus was collected from five areas including Deqin (DQ), Xianggelila (XGLL), Lijiang (LJ), Jianchuan (JC), and Dali (DL), we used 16S rRNA sequencing technology combined with physiological and morphological methods to study the intestinal microbiota diversity, abundance and community structure of the intestinal bacteria in winter, and to explore the influence of geographical factors, physiological indicators including food intake, resting metabolic rate (RMR), non-shivering thermogenesis (NST), neuropeptide Y (NPY), Agouti-Related Protein (AgRP), proopiomelanocortin (POMC), cocaine and amphetamine regulated transcription peptide (CART), and morphological indicators including body mass, body length and other nine indicators on the intestinal microflora diversity in E. miletus. The results showed that there were significant differences in metabolic indexes such as RMR, NST, NPY, AgRP, and morphological indexes such as body length, tail length and ear length among the five regions. Bacterial community in intestinal tract of E. miletus mainly includes three phyla, of which Firmicutes is the dominant phyla, followed by Bacteroidetes and Tenericutes. At the genus level, the dominant bacterial genera were S24-7(UG), Clostridiales (UG), and Lachnospiraceae (UG), etc. α diversity of intestinal microorganisms in DL and JC were significantly different from that in the other three regions. Genera of intestinal microorganisms in DL and JC were also the most. Moreover, Bacteroides, Ruminococcus, and Treponema could affect energy metabolism in E. miletus, which were closely related to the environment in which they lived. All of these results indicated that different areas in Hengduan Mountain had certain effects on the structure of intestinal microbial community in E. miletus, which were responded positively to changes in food abundance and other environmental factors. Furthermore, Firmicutes and Bacteroidetes play an important role in the body mass regulation in E. miletus.

Identification of CD8+ T Cell Related Biomarkers in Ovarian Cancer.

Background: Immunotherapy is a promising strategy for ovarian cancer (OC), and this study aims to identify biomarkers related to CD8+ T cell infiltration to further discover the potential therapeutic target. Methods: Three datasets with OC transcriptomic data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Two immunotherapy treated cohorts were obtained from the Single Cell Portal and Mariathasan's study. The infiltration fraction of immune cells was quantified using three different algorithms, Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT), and microenvironment cell populations counter (MCPcounter), and single-sample GSEA (ssGSEA). Weighted gene co-expression network analysis (WGCNA) was applied to identify the co-expression modules and related genes. The nonnegative matrix factorization (NMF) method was proposed for sample classification. The mutation analysis was conducted using the "maftools" R package. Key molecular markers with implications for prognosis were screened by univariate COX regression analysis and K-M survival analysis, which were further determined by the receiver operating characteristic (ROC) curve. Results: A total of 313 candidate CD8+ T cell-related genes were identified by taking the intersection from the TCGA-OV and GSE140082 cohorts. The NMF clustering analysis suggested that patients in the TCGA-OV cohort were divided into two clusters and the Cluster 1 group showed a worse prognosis. In contrast, Cluster 2 had higher amounts of immune cell infiltration, elevated ssGSEA scores in immunotherapy, and a higher mutation burden. CSMD3, MACF1, PDE4DIP, and OBSCN were more frequently mutated in Cluster 1, while SYNE2 was more frequently mutated in Cluster 2. CD38 and CXCL13 were identified by univariate COX regression analysis and K-M survival analysis in the TCGA-OV cohort, which were further externally validated in GSE140082 and GSE32062. Of note, patients with lower CXCL13 expression showed a worse prognosis and the CR/PR group had a higher expression of CXCL13 in two immunotherapy treated cohorts. Conclusion: OC patients with different CD8+ T cell infiltration had distinct clinical prognoses. CXCL13 might be a potential therapeutic target for the treatment of OC.

SiO2 Microsphere Array Coated by Ag Nanoparticles as Raman Enhancement Sensor with High Sensitivity and High Stability.

In this paper, a monolayer SiO2 microsphere (MS) array was self-assembled on a silicon substrate, and monolayer dense silver nanoparticles (AgNPs) with different particle sizes were transferred onto the single-layer SiO2 MS array using a liquid-liquid interface method. A double monolayer "Ag@SiO2" with high sensitivity and high uniformity was prepared as a surface-enhanced Raman scattering (SERS) substrate. The electromagnetic distribution on the Ag@SiO2 substrate was analyzed using the Lumerical FDTD (finite difference time domain) Solutions software and the corresponding theoretical enhancement factors were calculated. The experimental results show that a Ag@SiO2 sample with a AgNPs diameter of 30 nm has the maximal electric field value at the AgNPs gap. The limit of detection (LOD) is 10-16 mol/L for Rhodamine 6G (R6G) analytes and the analytical enhancement factor (AEF) can reach ~2.3 × 1013. Our sample also shows high uniformity, with the calculated relative standard deviation (RSD) of ~5.78%.

Roles of leptin on energy balance and thermoregulation in Eothenomys miletus.

Leptin is a hormone mainly synthesized and secreted by white adipose tissue (WAT), which regulates various physiological processes. To investigate the role of leptin in energy balance and thermoregulation in Eothenomys miletus, voles were randomly divided into leptin-injected and PBS-injected groups and placed at 25°C ± 1°C with a photoperiod of 12 L:12 D. They were housed under laboratory conditions for 28 days and compared in terms of body mass, food intake, water intake, core body temperature, interscapular skin temperature, resting metabolic rate (RMR), nonshivering thermogenesis (NST), liver and brown adipose tissue (BAT) thermogenic activity, and serum hormone levels. The results showed that leptin injection decreased body mass, body fat, food intake, and water intake. But it had no significant effect on carcass protein. Leptin injection increased core body temperature, interscapular skin temperature, resting metabolic rate, non-shivering thermogenesis, mitochondrial protein content and cytochrome C oxidase (COX) activity in liver and brown adipose tissue, uncoupling protein 1 (UCP1) content and thyroxin 5'-deiodinase (T45'-DII) activity in brown adipose tissue significantly. Serum leptin, triiodothyronine (T3), thyrotropin-releasing hormone (TRH) and corticotropin-releasing hormone (CRH) concentrations were also increased significantly. Correlation analysis showed that serum leptin levels were positively correlated with core body temperature, body mass loss, uncoupling protein 1 content, thyroxin 5'-deiodinase activity, nonshivering thermogenesis, and negatively correlated with food intake; thyroxin 5'-deiodinase and triiodothyronine levels were positively correlated, suggesting that thyroxin 5'-deiodinase may play an important role in leptin-induced thermogenesis in brown adipose tissue. In conclusion, our study shows that exogenous leptin is involved in the regulation of energy metabolism and thermoregulation in E. miletus, and thyroid hormone may play an important role in the process of leptin regulating energy balance in E. miletus.

Silencing Ribosomal Protein L22 Promotes Proliferation and Migration, and Inhibits Apoptosis of Gastric Cancer Cells by Regulating the Murine Double Minute 2-Protein 53 (MDM2-p53) Signaling Pathway.

BACKGROUND The aim of this study was to investigate the effect of ribosomal protein L22 (RPL22) on gastric cancer (GC) cell proliferation, migration, and apoptosis, and its correlation with the murine double minute 2-protein 53 (MDM2-p53) signaling pathway. MATERIAL AND METHODS The RPL22 expression in GC tissues and cells was detected by quantitative reverse transcription-polymerase chain reaction and western blotting. RPL22 was overexpressed in the MKN-45 cells by the transfection of a vector, pcDNA3.1 (pcDNA)-RPL22, whereas it was silenced in the MGC-803 cells by the transfection of short interfering (si) RNA (si-RPL22). Flow cytometric analysis, cell viability assays, wound healing assays, and transwell assays were utilized to explore the influences of RPL22 on the apoptosis, proliferation, migration, and invasion. Nutlin-3 (an MDM2-p53 inhibitor) was used to inhibit MDM2-p53 signaling. RESULTS The RPL22 expression was downregulated in GC tissues and cells. It was significantly lower in the advanced GC tissues than in the early GC tissues, and was significantly lower in the lymphatic metastatic tissues than in the non-lymphatic metastatic tissues. The transfection of si-RPL22 accelerated the ability of GC cells to proliferate and metastasize, whereas apoptosis was dampened. The transfection of pcDNA-RPL22 exerted the opposite effect on the GC cells; MDM2 expression was upregulated in RPL22-silenced GC cells, while the expression of p53 was downregulated. In vitro, treatment with nutlin-3 reversed the promoting effects of si-RPL22 on GC progression. CONCLUSIONS In vitro, the silencing of RPL22 aggravates GC by regulating the MDM2-p53 signaling pathway.

Amplification of the human epidermal growth factor receptor 2 (HER2) gene is associated with a microsatellite stable status in Chinese gastric cancer patients.

BACKGROUND: Gastric cancer (GC) is one of the most common cancers worldwide. However, little is known about the combination of HER2 amplification and microsatellite instability (MSI) status in GC. This study aimed to analyze the correlation of HER2 amplification with microsatellite instability (MSI) status, clinical characteristics, and the tumor mutational burden (TMB) of patients. METHODS: A total of 192 gastric cancer (GC) patients were enrolled in this cohort. To analyze genomic alterations (GAs), deep sequencing was performed on 450 target cancer genes. TMB was measured by an in-house algorithm. MSI status was inferred based on the MANTIS (Microsatellite Analysis for Normal-Tumor InStability) score. RESULTS: The most frequently amplified genes in the GC patients included cyclin E1 (CCNE1), human epidermal growth factor receptor 2 (HER2), fibroblast growth factor receptor 2 (FGFR2), cyclin D1 (CCND1), fibroblast growth factor 19 (FGF19), fibroblast growth factor 3 (FGF3), and fibroblast growth factor 4 (FGF4). The frequency of HER2 amplification was 9.38% (18/192). HER2 amplification was higher in females than in males (14.52% vs. 6.92%, respectively, P=0.091), however, MSI was higher in males compared to females (7.69% vs. 4.84%, respectively, P=0.46). HER2 amplification was higher in metastatic loci compared to primary lesions (23.08% vs. 8.38%, respectively, P=0.079) and was lower in patients with high TMB (TMB-H) compared to those with low TMB (TMB-L) (4.0% vs. 11.35%, respectively, P=0.12). While the frequency of MSI in metastatic foci was higher than that in primary lesions (15.38% vs. 6.15%, respectively, P=0.48), MSI status was highly associated with TMB-H (20% vs. 0%, respectively, P=3.66×10-7). Furthermore, HER2 amplification was negatively correlated with MSI status in Chinese GC patients. CONCLUSIONS: HER2 amplification was negatively correlated with TMB-H and MSI status, and MSI status was significantly associated with TMB-H in Chinese GC patients. These data suggested that HER2 amplification might be a negative indicator for GC immunotherapy.

Optimized Tapered Fiber Decorated by Ag Nanoparticles for Raman Measurement with High Sensitivity.

A tapered fiber decorated by Ag nanoparticles is prepared as a surface-enhanced Raman scattering (SERS) substrate. There are two key parameters during the preparation process, the fiber cone angle and the density of decorated AgNPs on the fiber tip surface. Their theoretical analysis on the forming mechanism and the optimization process is studied in detail. The tapered fibers with angles from 0.5 to 30° are successfully prepared, with a chemical method in a small tube using a bending interface. AgNPs with different densities are decorated on the surface of the tapered fibers with an electrostatic adsorption method. The optimized tapered fiber SERS probe with an angle of 12° and AgNPs density of 26.67% provides the detection of Rhodamine 6G (R6G) with 10-10 mol/L.

Role of Oxidative DNA Damage and Repair in Atrial Fibrillation and Ischemic Heart Disease.

Atrial fibrillation (AF) and ischemic heart disease (IHD) represent the two most common clinical cardiac diseases, characterized by angina, arrhythmia, myocardial damage, and cardiac dysfunction, significantly contributing to cardiovascular morbidity and mortality and posing a heavy socio-economic burden on society worldwide. Current treatments of these two diseases are mainly symptomatic and lack efficacy. There is thus an urgent need to develop novel therapies based on the underlying pathophysiological mechanisms. Emerging evidence indicates that oxidative DNA damage might be a major underlying mechanism that promotes a variety of cardiac diseases, including AF and IHD. Antioxidants, nicotinamide adenine dinucleotide (NAD+) boosters, and enzymes involved in oxidative DNA repair processes have been shown to attenuate oxidative damage to DNA, making them potential therapeutic targets for AF and IHD. In this review, we first summarize the main molecular mechanisms responsible for oxidative DNA damage and repair both in nuclei and mitochondria, then describe the effects of oxidative DNA damage on the development of AF and IHD, and finally discuss potential targets for oxidative DNA repair-based therapeutic approaches for these two cardiac diseases.

Metabonomics of white adipose tissue and brown adipose tissue in Tupaia belangeri during cold acclimation.

In the present study, liquid chromatography-mass spectrometer (LC-MS) was used to perform untargeted metabolomics analysis of white adipose tissue (WAT) and brown adipose tissue (BAT) in Tupaia belangeri during cold acclimation. Differences in biochemical composition between WAT and BAT were compared. Clarifying how the two adipose tissues respond to the lower temperature in terms of metabolomics, which elucidate the metabolic process and energy homeostasis regulation mechanism in T. belangeri. The results showed that there were 34, 59 and 20 differential metabolites in the WAT, BAT and WAT compared with BAT, respectively. WAT and BAT had significant differences in various metabolic pathways such as sugar metabolism, amino acid metabolism, lipid metabolism, and nucleotide metabolism, which were closely related to the different biological roles of the two tissues. Increasing the concentrations of intermediate products of tricarboxylic acid (TCA) cycle, pyruvic acid, and phosphoenolpyruvic acid (PEP) in WAT and increasing the metabolites in TCA cycle, glyoxylate and dicarboxylate metabolism pathways in BAT, likely to increase the thermogenic capacity in T. belangeri in response to cold stress. There were more differential metabolic pathways in BAT during cold acclimation than that of in WAT. Moreover, compared to WAT, BAT responds to cold stress by adjusting the concentration of nucleotide metabolites.

Encorafenib enhances TRAIL-induced apoptosis of colorectal cancer cells dependent on p53/PUMA signaling.

TRAIL has been demonstrated to play a critical role in the apoptosis of colorectal cancer (CRC) cells, but drug resistance markedly restricts its therapeutic effects. Objectives: This study aims to investigate whether encorafenib can enhance TRAIL-induced apoptosis of colorectal cancer cells and the underlying mechanism. TRAIL was first used to induce CRC cells. CCK-8 assays were conducted for detecting cell viability of TRAIL-induced CRC cells with encorafenib treatment. Flow cytometry was used to detect the cell apoptosis of CRC cells and western blot was used to measure the expressions of apoptosis-related proteins. The expressions of DR4, DR5, p53, and PUMA were then evaluated by qPCR and western blot. After transfecting the interference plasmid of p53 into CRC cells, the expressions of PUMA and DR5 were further explored. TRAIL reduced the cell viability of CRC cells, and the inhibition was further reinforced under co-treatment of TRAIL and encorafenib. Encorafenib also triggered the promotion of CRC cell apoptosis induced by TRAIL. It was also found that encorafenib exerted its promoting effects on cell apoptosis of CRC cells via the elevation of DR5. Besides, encorafenib administration promoted the expression levels of p53 and PUMA in TRAIL-induced CRC cells. Furthermore, p53 knockdown attenuated the expression of PUMA and DR5 in TRAIL-induced CRC cells treated with encorafenib. This study indicates that encorafenib stimulates TRAIL-induced apoptosis of CRC cells dependent on p53/PUMA signaling, which may provide instructions for the treatment of CRC.

Long Non-Coding RNA BLACAT1 Promotes the Tumorigenesis of Gastric Cancer by Sponging microRNA-149-5p and Targeting KIF2A.

OBJECTIVE: Gastric cancer (GC) is a gastrointestinal tumor. This study is aimed to explore the regulatory mechanism of long non-coding RNA BLACAT1 (BLACAT1)/microRNA-149-5p (miR-149-5p)/KIF2A cascade on GC. METHODS: The expression of BLACAT1, miR-149-5p and KIF2A in GC was detected by qRT-PCR. The proliferation, migration and invasion of GC cells in vitro were analyzed by MTT, wound-healing and transwell assay, respectively. The xenograft tumor model was constructed in nude mice to confirm the inhibition effect of BLACAT1 knockdown on GC in vivo. Then, dual-luciferase reporter assay was used to detect the interactions among BLACAT1, miR-149-5p and KIF2A. Western blot assay was performed to determine the protein expression of KIF2A. RESULTS: The expression of BLACAT1 and KIF2A was up-regulated in GC, but miR-149-5p expression was down-regulated. Silencing of BLACAT1 retarded the proliferation, migration and invasion of GC cells in vitro and the growth of tumor xenograft in vivo. Moreover, BLACAT1 acted as the molecular sponge of miR-149-5p to up-regulate KIF2A expression. At last, feedback experiments suggested that BLACAT1 accelerated the proliferation, migration and invasion of GC cells by regulating miR-149-5p/KIF2A axis. CONCLUSION: BLACAT1 facilitated the tumorigenesis of GC through regulating miR-149-5p/KIF2A axis, which indicated BLACAT1/miR-149-5p/KIF2A cascade may be a new therapeutic target.