Unexpected Cyclization Product Discovery from the Photoinduced Bioconjugation Chemistry between Tetrazole and Amine.

Bioconjugation chemistry has emerged as a powerful tool for the modification of diverse biomolecules under mild conditions. Tetrazole, initially proposed as a bioorthogonal photoclick handle for 1,3-dipolar cyclization with alkenes, was later demonstrated to possess broader photoreactivity with carboxylic acids, serving as a versatile bioconjugation and photoaffinity labeling probe. In this study, we unexpectedly discovered and validated the photoreactivity between tetrazole and primary amine to afford a new 1,2,4-triazole cyclization product. Given the significance of functionalized N-heterocycles in medicinal chemistry, we successfully harnessed the serendipitously discovered reaction to synthesize both pharmacologically relevant DNA-encoded chemical libraries (DELs) and small molecule compounds bearing 1,2,4-triazole scaffolds. Furthermore, the mild reaction conditions and stable 1,2,4-triazole linkage found broad application in photoinduced bioconjugation scenarios, spanning from intramolecular peptide macrocyclization and templated DNA reaction cross-linking to intermolecular photoaffinity labeling of proteins. Triazole cross-linking products on lysine side chains were identified in tetrazole-labeled proteins, refining the comprehensive understanding of the photo-cross-linking profiles of tetrazole-based probes. Altogether, this tetrazole-amine bioconjugation expands the current bioconjugation toolbox and creates new possibilities at the interface of medicinal chemistry and chemical biology.

Performance analysis for OFDM-based multi-carrier continuous-variable quantum key distribution with an arbitrary modulation protocol.

Multi-carrier continuous-variable quantum key distribution (CV-QKD) is considered to be a promising way to boost the secret key rate (SKR) over the existing single-carrier CV-QKD scheme. However, the extra excess noise induced in the imperfect multi-carrier quantum state preparation process of N subcarriers will limit the performance of the system. Here, a systematic modulation noise model is proposed for the multi-carrier CV-QKD based on the orthogonal frequency division multiplexing (OFDM). Subsequently, the performance of multi-carrier CV-QKD with arbitrary modulation protocol (e.g. QPSK, 256QAM and Gaussian modulation protocol) can be quantitatively evaluated by combining the security analysis method of the single-carrier CV-QKD. Under practical system parameters, the simulation results show that the SKR of the multi-carrier CV-QKD can still be significantly improved by increasing the carrier number N even with imperfect practical modulations. Specifically, the total SKR of multi-carrier CV-QKD can be optimized by carefully choosing N. The proposed model provides a feasible theoretical framework for the future multi-carrier CV-QKD experimental implementation.

Effect of different free-range systems on the growth performance, carcass traits, and meat quality of Yangzhou geese.

This study was conducted to investigate the effects of different free-range systems on the growth performance, carcass traits, and meat quality of geese. Grass pasture zones in the study area were selected, and 28 d-old male Yangzhou geese with similar body weights (1.57 ± 0.12 kg) were randomly allocated to one of three conditions: (A) free-range conditions in the apron area during 9:00 a.m.-4:00 p.m. (10-20 m from shed with grass pasture); (B) free-range conditions in the outer range from 9:00 a.m. to 4:00 p.m. (beyond 50 m from shed with grass pasture); and (C) barn system. Free range-reared geese had higher weight gain after 42 days of age than barn-reared geese, regardless of the range area. A lower feed conversion ratio was found in outer range-reared and apron area-reared geese from 28 to 63 days of age. In addition, the highest percentages of leg and breast muscle weights were observed in outer range-reared and apron area-reared geese, respectively. Finally, outer-range rearing resulted in a lower pH and lower moisture content. Therefore, these data suggest that the outer range system benefits growth performance and feed conversion ratio of geese and results in a higher percentage of leg muscle weight, lower pH, and lower moisture content.

The roles of long non-coding RNAs in ocular diseases.

In recent years, lncRNAs have been shown to regulate gene expression at the epigenetic, transcriptional and translational level, thus exerting various functions in biological and pathological processes involving cell proliferation, apoptosis, cell cycle and immune response. An increasing number of researches have unveiled that lncRNAs are dysregulated in pathogenesis and the development of different ocular diseases, such as glaucoma, cataract, retinal disease and ocular tumors. Also, it has been reported that lncRNAs may exert significant roles in various ocular diseases. Here, we summarized the functions of lncRNAs on relevant ocular diseases and further clarified their mechanisms. Here, several previous studies with detailed information of lncRNAs which have been proved to be the diagnostic or prognostic biomarkers and potential therapeutic targets were included. Also, it is our hope to provide a thorough knowledge of the functions of lncRNAs in eye diseases and the methods by which lncRNAs can influence ocular diseases.

High-speed Gaussian-modulated continuous-variable quantum key distribution with a local local oscillator based on pilot-tone-assisted phase compensation.

A high-speed Gaussian-modulated continuous-variable quantum key distribution (CVQKD) with a local local oscillator (LLO) is experimentally demonstrated based on pilot-tone-assisted phase compensation. In the proposed scheme, the frequency-multiplexing and polarization-multiplexing techniques are used for the separate transmission and heterodyne detection between quantum signal and pilot tone, guaranteeing no crosstalk from strong pilot tone to weak quantum signal and different detection requirements of low-noise for quantum signal and high-saturation limitation for pilot tone. Moreover, compared with the conventional CVQKD based on homodyne detection, the proposed LLO-CVQKD scheme can measure X and P quadrature simultaneously using heterodyne detection without need of extra random basis selection. Besides, the phase noise, which contains the fast-drift phase noise due to the relative phase of two independent lasers and the slow-drift phase noise introduced by quantum channel disturbance, has been compensated experimentally in real time, so that a low level of excess noise with a 25 km optical fiber channel (with 5 dB loss) is obtained for the achievable secure key rate of 7.04 Mbps in the asymptotic regime and 1.85 Mbps under the finite-size block of 107.

Competitive Sorption of CO2 with Gas Mixtures in Nanoporous Shale for Enhanced Gas Recovery from Density Functional Theory.

CO2 competitive sorption with shale gas under various conditions from simple to complex pore characteristics is studied using a molecular density functional theory (DFT) that reduces to perturbed chain-statistical associating fluid theory in the bulk fluid region. The DFT model is first verified by grand canonical Monte Carlo simulation in graphite slit pores for pure and binary component systems at different temperatures, pressures, pore sizes, and bulk gas compositions for methane/ethane with CO2. Then, the model is utilized in multicomponent systems that include CH4, C2H6, and C3+ components of different compositions. It is shown that the selectivity of CO2 decreases with increases in temperature, pressure, nanopore size, and average molecular weight of shale gas. Extending the model to more realistic situations, we consider the impact of water present in the pore and consider the effect of permeation of fluid molecules into the kerogen that forms the pore walls. The water-graphite interaction is calibrated with contact angle from molecular simulation data from the literature. The kerogen pore model prediction of gas absolute sorption is compared with experimental and molecular simulation values in the literature. It is shown that the presence of water reduces the CO2 adsorption but improves the CO2 selectivity. The dissolution of gases into the kerogen matrix also leads to the increase in CO2 selectivity. The effect of kerogen type and maturity on the gas sorption amount and CO2 selectivity is also studied. The associated mechanisms are discussed to provide fundamental understanding for gas recovery by CO2.

Thermodynamics, Microstructures, and Solubilization of Block Copolymer Micelles by Density Functional Theory.

Block copolymer micelle is one of the most versatile self-assembled structures with applications in drug delivery, cosmetic products, and micellar-enhanced ultrafiltration. The key to design an effective block copolymer to form micelles is to understand how molecular architecture affects critical micelle concentrations, micellar dimensions, and partitioning of solute into the micelle. In this work, we studied micelles from nonionic block copolymers using interfacial statistical associating fluid theory a density functional theory, which explicitly includes block copolymer-water hydrogen bonding and water-water hydrogen bonding. We are able to predict and explain how micellar thermodynamic properties depend on polymer chain architecture. Dimension and aggregation of micelles are investigated for block copolymers with different hyrophobes and hydrophiles. The effects of temperature and pressure on micelle stability are also captured by the theory. The enhanced solubility of hydrophobic substance in water by micelle loading is demonstrated, and predicted solute distribution answers the question about the locus of benzene in micelles from a theoretical perspective.

Exosome-mediated transfer of CLIC1 contributes to the vincristine-resistance in gastric cancer.

Our previous study shows that high Chloride intracellular channel 1 (CLIC1) expression can efficiently enhance invasion and migration of gastric cancer (GC) cells in vitro. Growing evidences have found that exosomes are involved in chemotherapy resistance in several cancers including GC. We aimed to evaluate the effect of the exosome-mediated transfer of CLIC1 in the vincristine-resistance of GC. The effect of exosome-mediated transfer of CLIC1 on the development of resistance to vincristine in GC cell line SGC-7901 and the potential underlying mechanisms were investigated by Cell Counting Kit-8 (CCK8), RT-PCR, and Western blotting. Exosomes were isolated from cell supernatants by differential ultracentrifugation. Comparing with SGC-7901, the expression level of CLIC1 is higher in vincristine­resistant cell line SGC-7901/VCR (P < 0.05). After silencing the expression of CLIC1 by RNA interference, the half inhibition concentration (IC50) to vincristine decreased significantly in SGC-7901/VCR, and the expression of CLIC1 decreased significantly in exosomes from SGC-7901/VCR. After 48 h co-culturing with exosomes from SGC-7901/VCR, the IC50 to vincristine in SGC-7901 increased significantly, and the expression of CLIC1, P-gp, and Bcl-2 were significantly up-regulated. CLIC1 was closely associated with the resistance to vincristine in GC, and exosome-mediated transfer of CLIC1 could induce the development of resistance to vincristine in vitro. The possible mechanism was related to up-regulated P-gp and Bcl-2. However, in vivo study was needed to confirm the results in future.

Sarcopenia is Associated with Perioperative Outcomes in Gastric Cancer Patients Undergoing Gastrectomy.

BACKGROUND: Sarcopenia is a syndrome in which skeletal muscle reduction is the main manifestation of age-related and/or disease-related malnutrition associated with postoperative complications and mortality. OBJECTIVES: The aim of the current study was to investigate the association between sarcopenia and postoperative complications as well as the nutrition risk of patients with gastric cancer (GC) who received gastrectomy. In addition, a comparative analysis was performed to evaluate the diagnostic accuracy of total psoas muscle area (TPA) and skeletal muscle area (SMA) in sarcopenia. METHODS: Preoperative computed tomography scans were obtained from 279 GC patients who received a gastrectomy from June 2011 to May 2016. TPA and SMA at the level of the third lumbar vertebra (L3) were used as the sarcopenia diagnostic index. Patients were diagnosed with sarcopenia via the total psoas muscle index (TPI) and skeletal muscle index (SMI) methods. TPI and SMI were normalized with the square of the patient's height (m2) by TPA and SMA. The Clavien-Dindo complications score system was used to classify the complication extent after gastrectomy. Univariate and multivariate logistic regression analyses were carried out to evaluate the risk factors for postoperative complications. RESULTS: A total of 68 and 125 patients were diagnosed with sarcopenia by TPI and SMI, respectively. Eighty-eight (31.5%) patients experienced postoperative complications. Patients with sarcopenia also had a significantly extended postoperative stay (TPI-sarcopenia, 15.0 days vs. non-sarcopenia, 11.0 days, p < 0.001; and SMI-sarcopenia, 14.0 days vs. non-sarcopenia, 11.0 days, p < 0.001) and hospital stay (TPI-sarcopenia, 22.5 days vs. non-sarcopenia, 17.0 days, p < 0.001; and SMI-sarcopenia, 21.0 days vs. non-sarcopenia, 16.5 days, p < 0.001). Multivariate logistic analysis showed that both TPI-sarcopenia (OR 7.561, p < 0.001) and SMI-sarcopenia (OR 10.085, p < 0.001) were associated with the risk of postoperative complications. Furthermore, univariate analysis showed a high correlation between nutrition risk screening 2002 (NRS2002) and sarcopenia (p < 0.001). A total of 54 (79.4%) of the 68 patients who were classified as having sarcopenia by TPI and 94 (75.3%) of the 125 patients who were classified as having sarcopenia by SMI were diagnosed with nutritional risk. CONCLUSIONS: Sarcopenia is associated with the total length of hospital stay, postoperative hospital stay, and severe complications in GC patients undergoing gastrectomy. Moreover, SMI may be a more meaningful index than TPI in reducing the rate of misdiagnosis and in predicting adverse perioperative risk. In addition, sarcopenia may cause severe malnutrition and increases perioperative adverse risk. Thus, both sarcopenia and the NRS2002 nutritional score should be assessed during preoperative nutritional screening and evaluation for GC patients.

Issues on peritoneal metastasis of gastric cancer: an update.

BACKGROUND: Peritoneal metastasis (PM) is one of the most common forms of metastasis with a very poor prognosis in patients with gastric cancer (GC). The mechanisms, diagnosis, and management of PM remain controversial. MAIN BODY: Stephen Paget's "seed-and-soil" hypothesis gives us an illustration of the mechanisms of PM. Recently, hematogenous metastasis and exosomes from GC are identified as novel mechanisms for PM. Diagnostic accuracy of conventional imaging modalities for PM is not satisfactory, but texture analysis may be a useful adjunct for the prediction of PM. Biological markers in peritoneal washings are helpful in identifying patients at high risk of PM, but many limitations remain to be overcome. Response of PM from systemic chemotherapy alone is very limited. However, conversion therapy is confirmed to be safe and able to prolong the survival of GC patients with PM. As an important part of conversion therapy, intraperitoneal chemotherapy with taxanes has become an ideal approach with several advantages. Additionally, gastrectomy should be considered in patients who would tolerate surgery if a remarkable response to chemotherapy was observed. CONCLUSION: Texture analysis is a reliable adjunct for the prediction of PM, and conversion therapy provides a new choice for GC patients with PM. The underlying mechanisms and new biological markers for GC patients with PM should be the direction of future studies. Furthermore, significant aspects of conversion therapy, such as timing and method of the operation, and the indications remain to be clarified.

CLIC1 Promotes the Progression of Gastric Cancer by Regulating the MAPK/AKT Pathways.

BACKGROUND/AIMS: Chloride intracellular channel 1 (CLIC1), which is a member of the chloride channel protein family, is associated with various human tumors. Recent studies have shown that CLIC1 is involved in the occurrence and development of gastric cancer (GC). However, the exact mechanism remains unclear in GC. METHODS: Effects of CLIC1 on the progression of GC in vivo and in vitro and the potential underlying mechanisms have been investigated by analysing 54 patients with GC, as well as human gastric cell lines SGC-7901 and MGC-803, utilizing proteomics, RT-PCR, Western blotting, flow cytometry, Cell invasion and migration assays and xenograft tumor models. RESULTS: Our study shows that CLIC1 knockdown by targeted-siRNA markedly inhibits GC cell invasion and migration and induces apoptosis in vitro. In total, 54 differentially expressed proteins were identified in GC cells SGC-7901 after CLIC1 silencing by isobaric tags for relative isotope labeled and absolute quantitation (iTRAQ) technology, including integrin α1 (ITGα1) and ITGα3. The expression levels of ITGα3, ITGαv, ITGß1 and Bcl-2 mRNA and protein were decreased significantly in GC cells after CLIC1 knockdown; ITGα1 and Fas were upregulated, but the level of survivin was not significantly different. GC growth and metabolism were decreased in vivo after CLIC1 silencing, but apoptosis was markedly increased. Further study showed that the expression levels of ITGα3, ITGαv and ITGß1, as well as AKT-phosphorylation, ERK-phosphorylation and p38-phosphorylation, were reduced in vivo after CLIC1 knockdown, while ITGα1 was upregulated. CONCLUSIONS: We speculate that CLIC1 may play an important role in the progression of GC, and its mechanism may be related to the regulation of integrin family proteins, which leads to the sequential regulation of the PI3K/AKT, MAPK/ERK and MAPK/p38 pathways.

Adsorption and Phase Behavior of Pure/Mixed Alkanes in Nanoslit Graphite Pores: An iSAFT Application.

The prediction of fluid phase behavior in nanoscale pores is critical for shale gas/oil development. In this work, we use a molecular density functional theory (DFT) to study the effect of molecular size and shape on partitioning to graphite nanopores as a model of shale. Here, interfacial statistical associating fluid theory (iSAFT) is applied to model alkane (C1 - C8) adsorption/desorption/phase behavior in graphite slit pores for both pure fluids and mixtures. The pure component parameters were fit to the bulk saturated liquid density and vapor pressure data in selected temperature ranges. The potential of interaction between the fluid and graphite is modeled with a Steele 10-4-3 potential that is fit to the potential of mean force from single-molecule simulations. Good agreement is found between theory and molecular simulation for the density distributions of pure components in slit pores. The critical properties of methane, ethane, and their mixtures as well as the shift in bubble point and dew point densities were studied, showing good agreement with simulation. The competitive adsorption of mixtures of normal and branched alkanes in graphite pores was also studied. Heavier components more strongly adsorb up to the point that the entropic penalty due to confinement reduces adsorption.

A Novel Scoring System for Diagnosing Acute Mesenteric Ischemia in the Emergency Ward.

BACKGROUND: Early diagnosis of acute mesenteric ischemia (AMI) based on clinical judgment has been proved to be too difficult. Therefore, it is important for identifying clinical parameters that can differentiate AMI from other acute abdomen upon presentation. METHODS: We analyzed a database of 106 consecutive patients admitted to the emergency ward for suspected AMI in whom diagnosis of AMI was confirmed by laparotomy, CT angiography or mesenteric angiography. The patients' demographics, previous history, clinical signs, results of laboratory investigations and ultrasonography were collected. Diagnostic cutoff value of quantitative indexes was derived from the receiver operating curve. Multivariate logistic regression was used to identify risk factors for AMI and formulated these risk factors into a scoring system. RESULTS: A total of 45 patients (42.5%) were confirmed to have AMI. Compared with other acute abdomen, AMI had significantly increased level of white blood cell (Odds ratio (OR) 16.11, 95% confidence interval (CI) 1.10-235.34), red cell distribution width (OR 27.65, 95% CI 1.53-501.02), mean platelet volume (OR 16.06, 95% CI 1.48-174.50) and D-dimer (OR 42.91, 95% CI 2.56-718.09). A diagnostic score was calculated by adding points assigned to the four parameters, and a cutoff score of four best identified patients with AMI, with sensitivity, specificity, positive and negative predictive values of 97.8, 91.8, 89.8 and 98.2%, respectively. CONCLUSION: This scoring system based on easily available parameters could be used as a useful tool for differentiating AMI from other acute abdomen in the emergency ward. Prospective studies with large sample remain needed for validating the results.

Modeling micelle formation and interfacial properties with iSAFT classical density functional theory.

Surfactants reduce the interfacial tension between phases, making them an important additive in a number of industrial and commercial applications from enhanced oil recovery to personal care products (e.g., shampoo and detergents). To help obtain a better understanding of the dependence of surfactantproperties on molecular structure, a classical density functional theory, also known as interfacial statistical associating fluid theory, has been applied to study the effects of surfactant architecture on micelle formation and interfacial properties for model nonionic surfactant/water/oil systems. In this approach, hydrogen bonding is explicitly included. To minimize the free energy, the system minimizes interactions between hydrophobic components and hydrophilic components with water molecules hydrating the surfactant head group. The theory predicts micellar structure, effects of surfactant architecture on critical micelle concentration, aggregation number, and interfacial tension isotherm of surfactant/water systems in qualitative agreement with experimental data. Furthermore, this model is applied to study swollen micelles and reverse swollen micelles that are necessary to understand the formation of a middle-phase microemulsion.

Exosomes in tumor microenvironment: novel transporters and biomarkers.

Tumor microenvironment (TME) plays an integral part in the biology of cancer, participating in tumor initiation, progression, and response to therapy. Exosome is an important part of TME. Exosomes are small vesicles formed in vesicular bodies with a diameter of 30-100 nm and a classic "cup" or "dish" morphology. They can contain microRNAs, mRNAs, DNA fragments and proteins, which are shuttled from a donor cell to recipient cells. Exosomes secreted from tumor cells are called tumor-derived (TD) exosomes. There is emerging evidence that TD exosomes can construct a fertile environment to support tumor proliferation, angiogenesis, invasion and premetastatic niche preparation. TD exosomes also may facilitate tumor growth and metastasis by inhibiting immune surveillance and by increasing chemoresistance via removal of chemotherapeutic drugs. Therefore, TD-exosomes might be potential targets for therapeutic interventions via their modification or removal. For example, exosomes can serve as specific delivery vehicles to tumors of drugs, small molecules, or agents of prevention and gene therapy. Furthermore, the biomarkers detected in exosomes of biological fluids imply a potential for exosomes in the early detection and diagnosis, prediction of therapeutic efficacy, and determining prognosis of cancer. Although exosomes may serve as cancer biomarkers and aid in the treatment of cancer, we have a long way to go before we can further enhance the anti-tumor therapy of exosomes and develop exosome-based cancer diagnostic and therapeutic strategies.

5.4 Gbps real time quantum random number generator with simple implementation.

We present a random number generation scheme based on measuring the phase fluctuations of a laser with a simple experimental setup. A simple model is established to analyze the randomness and the simulation result based on this model fits well with the experiment data. After the analog to digital sampling and suitable randomness extraction integrated in the field programmable gate array, the final random bits are delivered to a PC, realizing a 5.4 Gbps real time quantum random number generation. The final random bit sequences have passed all the NIST and DIEHARD tests.

Clinical impact of BRAF mutation on the diagnosis and prognosis of papillary thyroid carcinoma: a systematic review and meta-analysis.

BACKGROUND: The possible role of BRAF(V) (600E) mutation in the diagnosis and prognosis of papillary thyroid carcinoma (PTC) remains controversial. A systematic review to investigate the diagnostic and prognostic role of BRAF(V) (600E) mutation in patients with PTC is urgently needed. METHODS: A systematic review of relevant literatures was performed in PubMed, EMBASE and CENTRAL. The incremental accuracy (IA) of fine needle aspiration biopsy plus BRAF(V) (600E) mutation analysis over fine needle aspiration biopsy alone, and the statistical data about the association of BRAF(V) (600E) mutation and the prognosis of PTC (risk ratios (RR) for dichotomous data, standard mean differences for continuous data and hazard ratios (HRs) for disease-free survival (DFS) were pooled. Subgroup analysis was performed to explain the heterogeneities. RESULTS: A total of 67 studies were included. The pooled IA was 2% (95% confidence interval (CI): 0·5-4%). The pooled RR for gender, multifocality, lymph node metastasis, extrathyroidal invasion and pathological stage was 1·11 (95% CI: 0·98-1·25), 1·17 (95% CI: 1·09-1·24), 1·36 (95% CI: 1·20-1·53), 1·60 (95% CI: 1·41-1·82), and 1·49 (95% CI: 1·33-1·68), respectively. The pooled standard mean differences for age and tumour size were 0·14 (95% CI: 0·04-0·23) and 0·21 (95% CI: 0·1-0·32), respectively. The pooled HR for DFS was 1·96 (95% CI: 1·62-2·37). Subgroup analysis showed that these statistical results were affected by the geographical background of patients, study design and detection methods. CONCLUSIONS: BRAF(V) (600E) mutation analysis can not only be used in the diagnosis of PTC, but can also predict its prognosis.

PIWIL2 promotes progression of non-small cell lung cancer by inducing CDK2 and Cyclin A expression.

BACKGROUND: PIWI proteins have important roles in tumorigenesis due to their interaction with piRNAs. Recent studies suggest that PIWI proteins affect prognosis of various cancers. METHODS: In the present study, PIWI genes expression was assayed in non-small cell lung cancer (NSCLC). To determine the effects of PIWIL2 on NSCLC cells, overexpression and interference assays were performed using the A549 and H460 cell lines. The tumor formation model was performed to demonstrate the effects of PIWIL2 on tumor formation in vivo. RESULTS: PIWIL2 was increased both at the RNA and protein level in malignant cancer tissues compared with adjacent normal tissue. Moreover, increased PIWIL2 gene expression was negatively correlated with prognosis in NSCLC patients. Overexpression and interference of PIWIL2 promoted and depressed cell proliferation, respectively. Meanwhile, PIWIL2 interference arrested cells at the G2/M stage. In addition, we found that CDK2 and Cyclin A expression were correlated with PIWIL2 expression. Moreover, transfection of PIWIL2 promoted tumor growth in nude mice. CONCLUSION: Our findings shed light on the function of PIWIL2 in NSCLC and suggest potential prognostic and therapeutic value.

Anoikis-related genes as potential prognostic biomarkers in gastric cancer: A multilevel integrative analysis and predictive therapeutic value.

BACKGROUND: Gastric cancer (GC) is a frequent malignancy of the gastrointestinal tract. Exploring the potential anoikis mechanisms and pathways might facilitate GC research. PURPOSE: The authors aim to determine the significance of anoikis-related genes (ARGs) in GC prognosis and explore the regulatory mechanisms in epigenetics. METHODS: After describing the genetic and transcriptional alterations of ARGs, we searched differentially expressed genes (DEGs) from the cancer genome atlas and gene expression omnibus databases to identify major cancer marker pathways. The non-negative matrix factorisation algorithm, Lasso, and Cox regression analysis were used to construct a risk model, and we validated and assessed the nomogram. Based on multiple levels and online platforms, this research evaluated the regulatory relationship of ARGs with GC. RESULTS: Overexpression of ARGs is associated with poor prognosis, which modulates immune signalling and promotes anti-anoikis. The consistency of the DEGs clustering with weighted gene co-expression network analysis results and the nomogram containing 10 variable genes improved the clinical applicability of ARGs. In anti-anoikis mode, cytology, histology, and epigenetics could facilitate the analysis of immunophenotypes, tumour immune microenvironment (TIME), and treatment prognosis. CONCLUSION: A novel anoikis-related prognostic model for GC is constructed, and the significance of anoikis-related prognostic genes in the TIME and the metabolic pathways of tumours is initially explored.

Mechanical and Architectural Changes in Animal Bone Following Fast Neutron Irradiation.

ABSTRACT: Damage to healthy bone following exposure to ionizing radiation has been well documented for at least seven decades. Among the reported effects are a transient increase in stiffness and a reduction in breaking strength. These changes have been linked to a decrease in osteoblast proliferation and differentiation, inducing cell cycle arrest, reducing collagen production, and increasing sensitivity to apoptotic agents. In this work, we analyzed some mechanical and structural changes in compact costal bovine bone (Hereford breed, n = 9) subjected to escalating doses of fast neutrons from a 7 Li(p,n) 7 Be reaction. The mean neutron energy was 233 keV with calculated absorbed doses ranging from 0 to 4.05 ± 10% Gy. Samples were subjected to Young's Modulus (YM) and breaking strength testing with a Universal Testing Machine (UTM). We found an increase in Young's Modulus and a decrease in breaking strength as functions of increasing dose equivalent. Optical coherence tomography (OCT) revealed trabecular displacement into compact bone in an irradiated sample (D = 4.05 ± 10% Gy), with breaching of the endosteal wall. OCT further revealed a "crack-like" structure across the irradiated sample, potentially consistent with damage from a proton track resulting from an elastic (n,p) reaction. No previous report has been found on mechanical changes in large mammalian bones following fast neutron doses, nor of the OCT imaging of such samples.