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Recently, there has been a resurgence of interest in metabolic rewiring of tumors to identify clinically relevant genes. However, most of these studies have had either focused on individual tumors, or are too general, providing a broad outlook on overall changes. In this study, we have first curated an extensive list of genes encoding metabolic enzymes and metabolite transporters relevant to carbohydrate, fatty acid and amino acid oxidation and biosynthesis. Next, we have used publicly available transcriptomic data for 20 different tumor types from The Cancer Genome Atlas Network (TCGA) and focused on differential expression of these genes between tumor and adjacent normal tissue. Our study revealed major transcriptional alterations in genes that are involved in central metabolism. Most tumors exhibit upregulation in carbohydrate and amino acid transporters, increased glycolysis and pentose phosphate pathway, and decreased fatty acid and amino acid oxidation. On the other hand, the expression of genes of the tricarboxylic acid cycle, anaplerotic reactions and electron transport chain differed between tumors. Although most transcriptomic alterations were conserved across many tumor types suggesting the initiation of common regulatory programs, expression changes unique to specific tumors were also identified, which can provide gene expression fingerprints as potential biomarkers or drug targets. Our study also emphasizes the value of transcriptomic data in the deeper understanding of metabolic changes in diseases.Experimental detection of the Pt 5d densities of states in the valence band is conducted on a series of Pt-Ni alloys by high energy resolution valence-to-core X-ray emission spectroscopy (VTC-XES) at the Pt L3-edge. VTC-XES measurements reveal that the Pt d-band centroid shifts away from the Fermi level upon dilution, accompanied by concentration-dependent Pt d-band width. The competition between the strain effect and ligand effect is observed experimentally for the first time. It is found that the d-band widths in Pt3Ni and PtNi are broader than that of Pt metal due to compressive strain which overcompensates the effect of dilution, while it is narrower in PtNi3 where the ligand effect dominates. VTC-XES is demonstrated to be a powerful tool to study the Pt d-band contribution to the valence band of Pt-based bimetallic. The implication for the enhanced activity of Pt-Ni catalysts in oxygen reduction reaction is discussed.Shear-induced segregation, by particle size, is known in the flow of colloids and granular media, but is unexpected at the atomic level in the deformation of solid materials, especially at room temperature. In nanoscale wear tests of an Fe-based bulk metallic glass at room temperature, without significant surface heating, we find that intense shear localization under a scanned indenter tip can induce strong segregation of a dilute large-atom solute (Y) to planar regions that then crystallize as a Y-rich solid solution. There is stiffening of the material, and the underlying chemical and structural effects are characterized by transmission electron microscopy. The key influence of the soft Fe-Y interatomic interaction is investigated by ab-initio calculation. The driving force for the induced segregation, and its mechanisms, are considered by comparison with effects in other sheared media.Periodontal disease has been reported to be associated with diabetes mellitus. However, the direction of the association and the influence of bias are not clear. Thus, the aim of this systematic review and meta-analysis was to summarize the existing evidence on the bidirectional prospective association between periodontal disease and diabetes mellitus by accounting for the risk of bias of the original studies. The literature search was conducted on the electronic data sources PubMed and Web of Science up to February 9th, 2021. We included observational studies, which investigated the prospective association between diabetes mellitus and periodontal disease or vice versa. The risk of bias of the primary studies was evaluated by applying the Quality in Prognosis Studies (QUIPS) tool. Random effects models were used to calculate summary relative risk (SRR) with 95% CI. Subgroup analyses were applied to investigate heterogeneity and the robustness of the finding. In total, 15 studies were included . The SRR for incident diabetes mellitus was 1.26 (95% CI 1.12, 1.41; I2 71%, n = 10; participants = 427,620; identified cases = 114,361), when comparing individuals with periodontitis to individuals without periodontitis. The SRR for incident periodontitis was 1.24 (95% CI 1.13, 1.37; I2 92%, n = 7; participants = 295,804; identified cases > 22,500), comparing individuals with diabetes to individuals without diabetes. There were no significant differences between subgroups after stratification for risk of bias. The findings show a positive bidirectional association between periodontal disease and diabetes mellitus, and thus, underline the need for screening of patients with periodontitis regarding diabetes mellitus and vice versa. The main limitation of the study is the high unexplained heterogeneity between the studies including the different assessment methods of the disease diagnosis.Prediction models for population-based screening need, for global usage, to be resource-driven, involving predictors that are affordably resourced. Here, we report the development and validation of three resource-driven risk models to identify people with type 2 diabetes (T2DM) at risk of stage 3 CKD defined by a decline in estimated glomerular filtration rate (eGFR) to below 60 mL/min/1.73m2. The observational study cohort used for model development consisted of data from a primary care dataset of 20,510 multi-ethnic individuals with T2DM from London, UK (2007-2018). Discrimination and calibration of the resulting prediction models developed using cox regression were assessed using the c-statistic and calibration slope, respectively. Models were internally validated using tenfold cross-validation and externally validated on 13,346 primary care individuals from Wales, UK. The simplest model was simplified into a risk score to enable implementation in community-based medicine. The derived full model included demographic, laboratory parameters, medication-use, cardiovascular disease history (CVD) and sight threatening retinopathy status (STDR). Two less resource-intense models were developed by excluding CVD and STDR in the second model and HbA1c and HDL in the third model. All three 5-year risk models had good internal discrimination and calibration (optimism adjusted C-statistics were each 0.85 and calibration slopes 0.999-1.002). In Wales, models achieved excellent discrimination(c-statistics ranged 0.82-0.83). Calibration slopes at 5-years suggested models over-predicted risks, however were successfully updated to accommodate reduced incidence of stage 3 CKD in Wales, which improved their alignment with the observed rates in Wales (E/O ratios near to 1). The risk score demonstrated similar model performance compared to direct evaluation of the cox model. These resource-driven risk prediction models may enable universal screening for Stage 3 CKD to enable targeted early optimisation of risk factors for CKD.A novel specific spin-labeling strategy for bioactive molecules is presented for eptifibatide (integrilin) an antiplatelet aggregation inhibitor, which derives from the venom of certain rattlesnakes. By specifically labeling the disulfide bridge this molecule becomes accessible for analytical techniques such as Electron Paramagnetic Resonance (EPR) and solid state Dynamic Nuclear Polarization (DNP). The necessary spin-label was synthesized and inserted into the disulfide bridge of eptifibatide via reductive followed by insertion by a double Michael addition under physiological conditions. This procedure is universally applicable for disulfide containing biomolecules and is expected to preserve their tertiary structure with minimal change due to the small size of the label and restoring of the previous disulfide connection. HPLC and MS analysis show the successful introduction of the spin label and EPR spectroscopy confirms its activity. DNP-enhanced solid state NMR experiments show signal enhancement factors of up to 19 in 13C CP MAS experiments which corresponds to time saving factors of up to 361. This clearly shows the high potential of our new spin labeling strategy for the introduction of site selective radical spin labels into biomolecules and biosolids without compromising its conformational integrity for structural investigations employing solid-state DNP or advanced EPR techniques.COVID-19 global cases have climbed to more than 33 million, with over a million total deaths, as of September, 2020. Real-time massive SARS-CoV-2 whole genome sequencing is key to tracking chains of transmission and estimating the origin of disease outbreaks. Yet no methods have simultaneously achieved high precision, simple workflow, and low cost. We developed a high-precision, cost-efficient SARS-CoV-2 whole genome sequencing platform for COVID-19 genomic surveillance, CorvGenSurv (Coronavirus Genomic Surveillance). CorvGenSurv directly amplified viral RNA from COVID-19 patients' Nasopharyngeal/Oropharyngeal (NP/OP) swab specimens and sequenced the SARS-CoV-2 whole genome in three segments by long-read, high-throughput sequencing. Sequencing of the whole genome in three segments significantly reduced sequencing data waste, thereby preventing dropouts in genome coverage. We validated the precision of our pipeline by both control genomic RNA sequencing and Sanger sequencing. We produced near full-length whole genome sequences from individuals who were COVID-19 test positive during April to June 2020 in Los Angeles County, California, USA. These sequences were highly diverse in the G clade with nine novel amino acid mutations including NSP12-M755I and ORF8-V117F. With its readily adaptable design, CorvGenSurv grants wide access to genomic surveillance, permitting immediate public health response to sudden threats.This study aimed to evaluate the efficacy and safety of bone cement-augmented pedicle screw fixation for stage III Kümmell disease. Twenty-five patients with stage III Kümmell disease who received bone cement-augmented pedicle screw fixation at the First Affiliated Hospital of Guangzhou University of Chinese Medicine between June 2009 and December 2015 were enrolled. All patients were females with a history of osteoporosis. The vertebral Cobb angle (V-Cobb angle), the fixed segment Cobb Angle (S-Cobb angle), pelvic parameters, visual Analogue Scale (VAS) score, and Oswestry Disability Index (ODI) were assessed preoperatively, postoperatively and at the final follow-up. Complications, loosening rate, operation time, and intraoperative bleeding were recorded. The average lumbar vertebral density T-value was - 3.68 ± 0.71 SD, and the average age was 71.84 ± 5.39. The V-Cobb angle, S-Cobb angle, and Sagittal Vertical Axis (SVA) were significantly smaller postoperatively compared to the preoperative values. The VAS and ODI at 1 month after surgery were 3.60 ± 1.00 and 36.04 ± 6.12%, respectively, which were both significantly lower than before surgery (VAS 8.56 ± 1.04, ODI 77.80 ± 6.57%). Bone cement-augmented pedicle screw fixation is a safe and effective treatment for stage III Kümmell disease. It can effectively correct kyphosis, restore and maintain sagittal balance, and maintain spinal stability.
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