Reduced expression of MYC increases longevity and enhances healthspan.

MYC is a highly pleiotropic transcription factor whose deregulation promotes cancer. In contrast, we find that Myc haploinsufficient (Myc(+/-)) mice exhibit increased lifespan. They show resistance to several age-associated pathologies, including osteoporosis, cardiac fibrosis, and immunosenescence. They also appear to be more active, with a higher metabolic rate and healthier lipid metabolism. Transcriptomic analysis reveals a gene expression signature enriched for metabolic and immune processes. The ancestral role of MYC as a regulator of ribosome biogenesis is reflected in reduced protein translation, which is inversely correlated with longevity. We also observe changes in nutrient and energy sensing pathways, including reduced serum IGF-1, increased AMPK activity, and decreased AKT, TOR, and S6K activities. In contrast to observations in other longevity models, Myc(+/-) mice do not show improvements in stress management pathways. Our findings indicate that MYC activity has a significant impact on longevity and multiple aspects of mammalian healthspan.

Electrostatic Force Microscopic Characterization of Early Stage Carbon Deposition on Nickel Anodes in Solid Oxide Fuel Cells.

Carbon deposition on nickel anodes degrades the performance of solid oxide fuel cells that utilize hydrocarbon fuels. Nickel anodes with BaO nanoclusters deposited on the surface exhibit improved performance by delaying carbon deposition (i.e., coking). The goal of this research was to visualize early stage deposition of carbon on nickel surface and to identify the role BaO nanoclusters play in coking resistance. Electrostatic force microscopy was employed to spatially map carbon deposition on nickel foils patterned with BaO nanoclusters. Image analysis reveals that upon propane exposure initial carbon deposition occurs on the Ni surface at a distance from the BaO features. With continued exposure, carbon deposits penetrate into the BaO-modified regions. After extended exposure, carbon accumulates on and covers BaO. The morphology and spatial distribution of deposited carbon was found to be sensitive to experimental conditions.

An operando surface enhanced Raman spectroscopy (SERS) study of carbon deposition on SOFC anodes.

Thermally robust and chemically inert Ag@SiO2 nanoprobes are employed to provide the surface enhanced Raman scattering (SERS) effect for an in situ/operando study of the early stage of carbon deposition on nickel-based solid oxide fuel cell (SOFC) anodes. The enhanced sensitivity to carbon enables the detection of different stages of coking, offering insights into intrinsic coking tolerance of material surfaces. Application of a thin coating of gadolinium doped ceria (GDC) enhances the resistance to coking of nickel surfaces. The electrochemically active Ni-YSZ interface appears to be more active for hydrocarbon reforming, resulting in the accumulation of different hydrocarbon molecules, which can be readily removed upon the application of an anodic current. Operando SERS is a powerful tool for the mechanistic study of coking in SOFC systems. It is also applicable to the study of other catalytic and electrochemical processes in a wide range of conditions.

A nomogram for predicting survival in patients with gastrointestinal stromal tumor: a study based on the surveillance, epidemiology, and end results database.

Purpose: The objective of this investigation was to construct and validate a nomogram for prognosticating cancer-specific survival (CSS) in patients afflicted with gastrointestinal stromal tumor (GIST) at 3-, 5-, and 8-years post-diagnosis. Methods: Data pertaining to patients diagnosed with GIST were acquired from the Surveillance, Epidemiology, and End Results (SEER) database. Through random selection, a training cohort (70%) and a validation cohort (30%) were established from the patient population. Employing a backward stepwise Cox regression model, independent prognostic factors were identified. Subsequently, these factors were incorporated into the nomogram to forecast CSS rates at 3-, 5-, and 8-years following diagnosis. The nomogram's performance was assessed using indicators such as the consistency index (C-index), the area under the time-dependent receiver operating characteristic curve (AUC), the net reclassification improvement (NRI), the integrated discrimination improvement (IDI), calibration curves, and decision-curve analysis (DCA). Results: This investigation encompassed a cohort of 3,062 GIST patients. By analyzing the Cox regression model within the training cohort, nine prognostic factors were identified: age, sex, race, marital status, AJCC (American Joint Committee on Cancer) stage, surgical status, chemotherapy status, radiation status, and income status. The nomogram was subsequently developed and subjected to both internal and external validation. The nomogram exhibited favorable discrimination abilities, as evidenced by notably high C-indices and AUC values. Calibration curves confirmed the nomogram's reliability. Moreover, the nomogram outperformed the AJCC model, as demonstrated by enhanced NRI and IDI values. The DCA curves validated the clinical utility of the nomogram. Conclusion: The present study has successfully constructed and validated the initial nomogram for predicting prognosis in GIST patients. The nomogram's performance and practicality suggest its potential utility in clinical settings. Nevertheless, further external validation is warranted.

Upadacitinib for refractory ulcerative colitis with primary nonresponse to infliximab and vedolizumab: A case report.

BACKGROUND: Many patients with ulcerative colitis (UC) do not respond well to, or tolerate conventional and biological therapies. There is currently no consensus on the treatment of refractory UC. Studies have demonstrated that the selective Janus kinase 1 inhibitor upadacitinib, a small-molecule drug, is effective and safe for treating UC. However, no studies have revealed that upadacitinib is effective in treating refractory UC with primary nonresponse to infliximab and vedolizumab. CASE SUMMARY: We report the case of a 44-year-old male patient with a chief complaint of bloody diarrhoea with mucus and pus, in addition to dizziness. The patient had recurrent disease after receiving mesalazine, prednisone, azathioprine, infliximab and vedolizumab over four years. Based on the endoscopic findings and pathological biopsy, the patient was diagnosed with refractory UC. In particular, the patient showed primary nonresponse to infliximab and vedolizumab. Based on the patient's history and recurrent disease, we decided to administer upadacitinib. During hospitalisation, the patient was received upadacitinib under our guidance. Eight weeks after the initiation of upadacitinib treatment, the patient's symptoms and endoscopic findings improved significantly. No notable adverse reactions have been reported to date. CONCLUSION: Our case report suggests that upadacitinib may represent a valuable strategy for treating refractory UC with primary nonresponse.

Identification of the prognostic biomarkers and their correlations with immune infiltration in colorectal cancer through bioinformatics analysis and in vitro experiments.

Colorectal cancer (CRC) is the third most diagnosed malignancy and the second leading cause of cancer death. The objective was to identify novel hub genes that were helpful for prognosis and targeted therapy in CRC. GSE23878, GSE24514, GSE41657, GSE81582 were filtered from the gene expression omnibus (GEO). Differentially expressed genes (DEGs) were identified through GEO2R, which were enriched in the GO term and KEGG pathway in DAVID. PPI network was constructed and analyzed using STRING and hub genes were screened out. The relationships between hub genes and prognoses in CRC were evaluated in GEPIA based on the cancer genome atlas (TCGA) and genotype-tissue expression (GTEx). The transcription factors and miRNA-mRNA interaction networks for hub genes were performed using miRnet and miRTarBase. The relationship between hub genes and tumor-infiltrating lymphocytes were analyzed in TIMER. The protein levels of hub genes were identified in HPA. The expression levels of hub gene in CRC and its effect on the biological effect of CRC cells were identified in vitro. As hub genes, the mRNA levels of BIRC5, CCNB1, KIF20A, NCAPG, and TPX2 were highly expressed in CRC and had excellent prognostic value. The BIRC5, CCNB1, KIF20A, NCAPG, and TPX2 were closely associated with transcription factors, miRNAs, tumor-infiltrating lymphocytes, suggesting their involvement in the regulation of CRC. BIRC5 highly expressed in CRC tissues and cells, and promoted the proliferation, migration, and invasion of CRC cells. BIRC5, CCNB1, KIF20A, NCAPG, and TPX2 are hub genes that serve as promising prognostic biomarkers in CRC. BIRC5 plays an important role in the development and progression of CRC.

Targeting proteasome enhances anticancer activity of oncolytic HSV-1 in colorectal cancer.

Herpes simplex virus 1 (HSV-1) has been widely used to treat various cancers, but its efficacy is limited. Studies indicated that combining HSV-1 and chemotherapy drugs can effectively improve the lethality of HSV-1 in tumor cells, which has a synergistic effect. Here, we explored the oncolytic effect and mechanism of bortezomib and HSV-1 on colorectal cancer cells, HCT116 and Caco-2. First, we selected four drugs to detect cell viability and found that the strongest HSV-1-promoting effect was achieved using bortezomib + HSV-1 treatment. Bortezomib combined with HSV-1 treatment significantly upregulated the expression of heat shock proteins, endoplasmic reticulum stress-related proteins and apoptosis-related proteins, while Bcl-2 was downregulated. JC-1 staining revealed that combining bortezomib and HSV-1 promotes cell apoptosis. In addition, bortezomib + oHSV-1 treatment effectively inhibit tumor growth. These results indicate that bortezomib combined with HSV-1 induce intense endoplasmic reticulum stress and activate the caspase-12 apoptosis pathway, killing tumor cells.

Application of surface enhanced Raman spectroscopy to the study of SOFC electrode surfaces.

SERS provided by sputtered silver was employed to detect trace amounts of chemical species on SOFC electrodes. Considerable enhancement of Raman signal and lowered detection threshold were shown for coked nickel surfaces, CeO(2) coatings, and cathode materials (LSM and LSCF), suggesting a viable approach to probing electrode degradation and surface catalytic mechanism.

[Polymorphism of vitamin D receptor gene FokI and susceptibility of prostatic cancer: a meta-analysis].

OBJECTIVE: To quantitatively investigate the association between the polymorphism of FokI of the VDR gene and the susceptibility of prostatic cancer. METHODS: Databases of Pubmed, EMBase, CBM, CNKI, VIP, and Wanfang Data were retrieved from the date they formed till May 2011. All randomized controlled clinical trials which matched both the inclusive criteria and exclusive criteria were subjected to meta-analysis, conducted on Revman 5.0.0 software. Stata 11.0 software was employed to process Begg's test. RESULTS: Ten studies were included. Total sample cases were 8360, with 3749 cases in the patient group and 4611 cases in the control group, respectively. The quantitative analysis showed there were no significantly differences between the polymorphism of VDR FokI alleles and the susceptibility of prostatic cancer (allele F to f: OR=1.00, 95% CI=0.94-1.06, P=0.96; genotypes FF/Ff to ff: OR=1.04, 95% CI=0.93-1.51, P=0.48; genotypes FF to Ff/ff: OR=0.97, 95% CI=0.89-1.06, P=0.53). Though one research on Indian people indicated that allele F was a risk factor for prostatic cancer, in Begg's test we observed relatively high publication bias. The subgroup analysis showed there were no significantly differences between the polymorphism of VDR FokI alleles and the susceptibility of prostatic cancer (allele F to f, white race: OR=0.91, 95% CI=0.88-1.02, P=0.17; yellow race: OR=1.09, 95% CI=0.95-1.24, P=0.22; Indian: OR=1.91, 95% CI=1.30-2.81, P=0.0009). CONCLUSION: VDR FokI allele F might be a protective factor for European and American Caucasians.

PAK5 facilitates the proliferation, invasion and migration in colorectal cancer cells.

Colorectal cancer (CRC) is the third-most common cancer around the world, accounting for approximately 10% of cancer-related mortality. Deeper molecular understanding of colorectal carcinogenesis will provide evidences for identification of early diagnostic indicators and novel therapeutic strategies for CRC treatment. The p21cdc42/rac1 -activated kinase 5 (PAK5) has been reported to be involved in a variety of tumor-promoting behaviors, whereas the underlying mechanisms of PAK5 in CRC progression are still obscure. Our current study revealed an upregulated expression of PAK5 in human CRC tissues as compared with normal adjacent biopsies, which was associated with tumor progression and metastasis. We further unraveled that inhibition of PAK5 was correlated with restrained proliferation, migration, and invasion of CRC cells in vitro and in vivo. Moreover, we showed an indispensable role of PAK5 in interacting with Cdc42 and Integrin ß1, ß3, thus, to facilitate the migration and invasion of CRC cells. Collectively, we pointed out a potential of PAK5 to serve as a novel therapeutic target in restricting CRC proliferation and metastasis. The uncovered mechanisms will deepen the comprehension with regard to the mechanisms of CRC progression, as well as providing new insights for therapeutic intervention in colorectal cancer.

Psychological assessment of children and adolescents with obesity.

Objective This study aimed to analyse the psychological conditions and behaviour of a group of Chinese children and adolescents with obesity, and to develop an intervention for these young patients. Methods A group of 72 patients aged from 4 to 15 years were recruited from an obesity clinic. Patients, or the parents of children younger than 12 years, filled out a series of self-report questionnaires, and the responses were recorded and analysed. Results The 72 children and adolescents with obesity had a mean age of 9.14 ± 2.18 years. The body mass index-z scores of children with obesity showed a significant positive correlation with the level of impulsive behaviour, motivational impulses, and cognitive instability (inattention). Children with obesity quickly responded with extreme emotions, and these responses were positively correlated with the degree of obesity (slight, intermediate, or severe obesity). Conclusion Children and adolescents being treated for obesity have many underlying psychological problems, including emotional instability and impulsivity, and are prone to extreme emotional-psychological problems. These difficulties are positively correlated with the degree of obesity. Therefore, clinical treatment of these problems requires not only use of medication, improved nutrition, and healthy exercise, but also addressing underlying psychologic problems.

The Anatomy Features and Variations of the Point Where Right Gastroepiploic Vein Flows into Superior Mesenteric Vein/Portal Vein: Anatomical Study of Catheterization of Portal Vein Infusion Chemotherapy.

INTRODUCTION: To study the anatomical features and classification of the angle between the right gastroepiploic vein (RGEV) and superior mesenteric vein/portal vein (SMV/PV) and to guide the catheterization of intraportal infusion chemotherapy through RGEV and reduce surgical complications. PATIENTS AND METHODS: A retrospective three-dimensional (3D) computed tomography study was undertaken on 200 consecutive subjects with or without hepatic malignant tumors with a dedicated workstation 3D-MIA (the improved MI-3DVS workstation) developed by ourselves to determine the prevalence of surgically significant angle between RGEV and SMV/PV anatomic variations and its classification. RESULTS: The mean value of the angles between the end of RGEV and SMV/PV (AERS/P) (200 cases) was 84.2° ± 23.8 (31.4°-151.5°): 40.6° ± 92.3 (-177.9° to 178.0°) (sagittal angle), 81.7° ± 29.8 (-79.3° to 160.7°) (coronal angle), and 10.5° ± 94.3 (-178.7° to 175.8°) (horizontal angle). The mean value of the angles between the right bend of RGEV and SMV/PV (ARRS/P) (168 cases) was 104.8° ± 26.1 (20.5°-159.7°):49.3° ± 117.8 (-175.3° to 179.5°) (sagittal angle), 103.5° ± 37.7 (-178.8° to 168.9°) (coronal angle), and 12.6° ± 102.8 (-179.9° to 179.2°) (horizontal angle). The AERS/P were classified into large angle group (32 cases, 16%), middle angle group (113 cases, 56.5%), and small angle group (55 cases, 27.5%) based on angle variations and risks of catheterization. CONCLUSIONS: Precognition of the variations of AERS/P and ARRS/P before surgery is useful during chemotherapy pump catheterizing through RGEV in reduction of surgical complications by modulating the angle and direction of RGEV running into SMV/PV properly.

Norwegian e-Infrastructure for Life Sciences (NeLS).

The Norwegian e-Infrastructure for Life Sciences (NeLS) has been developed by ELIXIR Norway to provide its users with a system enabling data storage, sharing, and analysis in a project-oriented fashion. The system is available through easy-to-use web interfaces, including the Galaxy workbench for data analysis and workflow execution. Users confident with a command-line interface and programming may also access it through Secure Shell (SSH) and application programming interfaces (APIs).  NeLS has been in production since 2015, with training and support provided by the help desk of ELIXIR Norway. Through collaboration with NorSeq, the national consortium for high-throughput sequencing, an integrated service is offered so that sequencing data generated in a research project is provided to the involved researchers through NeLS. Sensitive data, such as individual genomic sequencing data, are handled using the TSD (Services for Sensitive Data) platform provided by Sigma2 and the University of Oslo. NeLS integrates national e-infrastructure storage and computing resources, and is also integrated with the SEEK platform in order to store large data files produced by experiments described in SEEK.   In this article, we outline the architecture of NeLS and discuss possible directions for further development.

Procalcitonin levels in patients with positive blood culture, positive body fluid culture, sepsis, and severe sepsis: a cross-sectional study.

BACKGROUND: Numerous investigations on procalcitonin (PCT) have been carried out, although few with large sample size. To deal with the complexity of sepsis, an understanding of PCT in heterogeneous clinical conditions is required. METHODS: Hospitalized patients aged 10-79 years were included in this retrospective and cross-sectional study. PCT tests were assayed within 2 days of blood culture. RESULTS: A total of 2952 cases (from 2538 patients) were enrolled in this study, including 440 cases in the 'positive BC' group, 123 cases in the 'positive body fluid culture' group, and 2389 cases in the 'negative all culture' group. Median PCT values were 4.53 ng/ml, 2.95 ng/ml, and 0.49 ng/ml, respectively. Median PCT values in the gram-negative BC group and gram-positive BC group, respectively, were 6.99 ng/ml and 2.96 ng/ml. Median PCT values in the 'positive hydrothorax culture' group, 'positive ascites culture' group, 'positive bile culture' group, and 'positive cerebrospinal fluid culture' group, respectively, were 1.39 ng/ml, 8.32 ng/ml, 5.98 ng/ml, and 0.46 ng/ml. In all, 357 cases were classified into the 'sepsis' group, 150 of them were classified into the 'severe sepsis' group. Median PCT values were 5.63 ng/ml and 11.06 ng/ml, respectively. CONCLUSIONS: PCT could be used in clinical algorithms to diagnose positive infections and sepsis. Different PCT levels could be related to different kinds of microbemia, different infection sites, and differing severity of sepsis.

Synthetic phenylethanoid glycoside derivatives as potent neuroprotective agents.

Several phenylethanoid glycoside derivatives were designed and synthesized. Most of the synthetic compounds showed significant neuroprotective effects, including antioxidative and anti-apoptotic properties. Specifically, target compounds displayed potent effects against various toxicities such as H2O2 and 6-hydroxydopamine (6-OHDA) in PC12 cells. Among the synthetic derivatives, three compounds (5, 6, 8) exhibited much superior activities to the marketed drug Edaravone. The compounds were able to prevent the 6-OHDA-induced damage in PC12 cells in a dose-dependent manner. The anti-apoptotic effects could be observed via cell morphological changes. Moreover, the compounds significantly reduced the intracellular ROS increase resulting from 6-OHDA treatment. The preliminary structure-activity relationships were also explored. Compounds 5, 6, 8 may hold the potential as promising neuroprotective agents and new lead compounds for the treatment of neurodegenerative diseases or cerebral ischemia.

Well-organized raspberry-like Ag@Cu bimetal nanoparticles for highly reliable and reproducible surface-enhanced Raman scattering.

Surface-enhanced Raman scattering (SERS) is ideally suited for probing and mapping surface species and incipient phases on fuel cell electrodes because of its high sensitivity and surface-selectivity, potentially offering insights into the mechanisms of chemical and energy transformation processes. In particular, bimetal nanostructures of coinage metals (Au, Ag, and Cu) have attracted much attention as SERS-active agents due to their distinctive electromagnetic field enhancements originated from surface plasmon resonance. Here we report excellent SERS-active, raspberry-like nanostructures composed of a silver (Ag) nanoparticle core decorated with smaller copper (Cu) nanoparticles, which displayed enhanced and broadened UV-Vis absorption spectra. These unique Ag@Cu raspberry nanostructures enable us to use blue, green, and red light as the excitation laser source for surface-enhanced Raman spectroscopy (SERS) with a large enhancement factor (EF). A highly reliable SERS effect was demonstrated using Rhodamine 6G (R6G) molecules and a thin film of gadolinium doped ceria.

Probing and mapping electrode surfaces in solid oxide fuel cells.

Solid oxide fuel cells (SOFCs) are potentially the most efficient and cost-effective solution to utilization of a wide variety of fuels beyond hydrogen (1-7). The performance of SOFCs and the rates of many chemical and energy transformation processes in energy storage and conversion devices in general are limited primarily by charge and mass transfer along electrode surfaces and across interfaces. Unfortunately, the mechanistic understanding of these processes is still lacking, due largely to the difficulty of characterizing these processes under in situ conditions. This knowledge gap is a chief obstacle to SOFC commercialization. The development of tools for probing and mapping surface chemistries relevant to electrode reactions is vital to unraveling the mechanisms of surface processes and to achieving rational design of new electrode materials for more efficient energy storage and conversion(2). Among the relatively few in situ surface analysis methods, Raman spectroscopy can be performed even with high temperatures and harsh atmospheres, making it ideal for characterizing chemical processes relevant to SOFC anode performance and degradation(8-12). It can also be used alongside electrochemical measurements, potentially allowing direct correlation of electrochemistry to surface chemistry in an operating cell. Proper in situ Raman mapping measurements would be useful for pin-pointing important anode reaction mechanisms because of its sensitivity to the relevant species, including anode performance degradation through carbon deposition(8, 10, 13, 14) ("coking") and sulfur poisoning(11, 15) and the manner in which surface modifications stave off this degradation(16). The current work demonstrates significant progress towards this capability. In addition, the family of scanning probe microscopy (SPM) techniques provides a special approach to interrogate the electrode surface with nanoscale resolution. Besides the surface topography that is routinely collected by AFM and STM, other properties such as local electronic states, ion diffusion coefficient and surface potential can also be investigated(17-22). In this work, electrochemical measurements, Raman spectroscopy, and SPM were used in conjunction with a novel test electrode platform that consists of a Ni mesh electrode embedded in an yttria-stabilized zirconia (YSZ) electrolyte. Cell performance testing and impedance spectroscopy under fuel containing H2S was characterized, and Raman mapping was used to further elucidate the nature of sulfur poisoning. In situ Raman monitoring was used to investigate coking behavior. Finally, atomic force microscopy (AFM) and electrostatic force microscopy (EFM) were used to further visualize carbon deposition on the nanoscale. From this research, we desire to produce a more complete picture of the SOFC anode.