Life fingerprints of nuclear reactions in the body of animals

Nuclear reactions are a very important natural phenomenon in the universe. On the earth, cosmic rays constantly cause nuclear reactions. High energy beams created by medical devices also induce nuclear reactions in the human body. The biological role of these nuclear reactions is unknown. Here we show that the in vivo biological systems are exquisite and sophisticated by nature in influence on nuclear reactions and in resistance to radical damage in the body of live animals. In this study, photonuclear reactions in the body of live or dead animals were induced with 50-MeV irradiation. Tissue nuclear reactions were detected by positron emission tomography (PET) imaging of the induced beta+ activity. We found the unique tissue "fingerprints" of beta+ (the tremendous difference in beta+ activities and tissue distribution patterns among the individuals) are imprinted in all live animals. Within any individual, the tissue "fingerprints" of 15O and 11C are also very different. When the animal dies, the tissue "fingerprints" are lost. The biochemical, rather than physical, mechanisms could play a critical role in the phenomenon of tissue "fingerprints". Radiolytic radical attack caused millions-fold increases in 15O and 11C activities via different biochemical mechanisms, i.e. radical-mediated hydroxylation and peroxidation respectively, and more importantly the bio-molecular functions (such as the chemical reactivity and the solvent accessibility to radicals). In practice biologically for example, radical attack can therefore be imaged in vivo in live animals and humans using PET for life science research, disease prevention, and personalized radiation therapy based on an individual's bio-molecular response to ionizing radiation

Smart Hydrogel Grating Immunosensors for Highly Selective and Sensitive Detection of Human-IgG

This document is the Accepted Manuscript version of a Published Work that appeared in final form in [Industrial & Engineering Chemistry Research], copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see [https://pubs.acs.org/doi/10.1021/acs.iecr.0c00780].A smart diffraction grating immunosensor based on antigen-responsive hydrogel with enhanced analyte-induced volume changes is developed for highly selective and sensitive detection of human immunoglobulin G (H-IgG). The hydrogel grating contains poly(N-isopropylacrylamide) (PNIPAM) backbones with dual-cross-linking based on the dynamic complexation between pendent goat-anti-human IgG (GAH-IgG) and pendent H-IgG, and the covalent bonding by 4-arm-polyethylene glycol-acrylamide. Upon recognizing free H-IgG in the environment, the pendent GAH-IgG in the hydrogel can form new GAH-IgG/H-IgG complexes with free H-IgG because the binding constant of GAH-IgG to the free H-IgG is much larger than that of GAH-IgG to the pendent H-IgG and thus result in the decomplexation of GAH-IgG/H-IgG complexes with the pendent H-IgG as well as the swelling of hydrogel. The thermo-responsive PNIPAM backbones enable enhancement of H-IgG-responsive volume change of the proposed hydrogel grating via temperature regulation. Moreover, the cross-linker 4-arm-polyethylene glycol-acrylamide provides excellent transparency for the PNIPAM backbones during the volume change, which ensures output of diffracted optical signals with high intensity. With the elaborately designed molecular structures, the hydrogel grating allows highly selective and sensitive detection of [H-IgG] with a detection limit as low as 1.3 × 10–8 M. This work provides a simple and flexible strategy for developing diffraction grating immunosensors based on stimuli-responsive hydrogels for efficient detection of biomarkers

Comparison of survival, acute toxicities, and dose-volume parameters between intensity-modulated radiotherapy with or without internal target volume delineation method and three-dimensional conformal radiotherapy in cervical cancer patients:A retrospective and propensity score-matched analysis

BACKGROUND: To evaluate whether the use of the internal target volume (ITV) delineation method improves the performance of intensity‐modulated radiotherapy (IMRT) and three‐dimensional conformal radiotherapy (3DCRT) in terms of survival, acute toxicities, and dose–volume parameters. METHODS: A total number of 477 cervical cancer patients who received concurrent chemoradiotherapy (CCRT) from January 2012 to December 2016 were retrospectively analyzed. They were divided into four groups: the non‐ITV (N‐ITV) + IMRT, ITV + IMRT, N‐ITV + 3DCRT, and ITV + 3DCRT groups, with 76, 41, 327, and 33 patients, respectively. Survival analysis was performed with the Kaplan–Meier and the log‐rank tests, and acute toxicity analysis was performed with the chi‐squared test and the binary logistic regression test. Using the propensity score matching (PSM) method, 92 patients were matched among the four groups, and their dose–volume parameters were assessed with the Kruskal–Wallis method. RESULTS: The median follow‐up time was 49 months (1–119) for overall survival (OS). The 5‐year OS rate was 66.4%. The ITV delineation method was an independent prognostic factor for OS (HR [95% CI]: 0.52 [0.27, 0.98], p = 0.044) and progression‐free survival (PFS) (HR [95% CI]: 0.59 [0.36, 0.99], p = 0.045). The ITV + IMRT group had the lowest incidence rate (22%) and the N‐ITV + IMRT group had the highest incidence rate of grade ≥3 hematological toxicity (HT) (46.1%) among the four groups. The pelvic bone marrow relative V10, V20, and V30 in the N‐ITV + IMRT group was higher than those in the ITV + IMRT and N‐ITV + 3DCRT groups (p < 0.05). CONCLUSIONS: The use of ITV for IMRT treatment planning was associated with improved overall survival and progression‐free survival, with lower HT rate

The Lysine Demethylase dKDM2 Is Non-essential for Viability, but Regulates Circadian Rhythms in Drosophila

Post-translational modification of histones, such as histone methylation controlled by specific methyltransferases and demethylases, play critical roles in modulating chromatin dynamics and transcription in eukaryotes. Misregulation of histone methylation can lead to aberrant gene expression, thereby contributing to abnormal development and diseases such as cancer. As such, the mammalian lysine-specific demethylase 2 (KDM2) homologs, KDM2A and KDM2B, are either oncogenic or tumor suppressive depending on specific pathological contexts. However, the role of KDM2 proteins during development remains poorly understood. Unlike vertebrates, Drosophila has only one KDM2 homolog (dKDM2), but its functions in vivo remain elusive due to the complexities of the existing mutant alleles. To address this problem, we have generated two dKdm2 null alleles using the CRISPR/Cas9 technique. These dKdm2 homozygous mutants are fully viable and fertile, with no developmental defects observed under laboratory conditions. However, the dKdm2 null mutant adults display defects in circadian rhythms. Most of the dKdm2 mutants become arrhythmic under constant darkness, while the circadian period of the rhythmic mutant flies is approximately 1 h shorter than the control. Interestingly, lengthened circadian periods are observed when dKDM2 is overexpressed in circadian pacemaker neurons. Taken together, these results demonstrate that dKdm2 is not essential for viability; instead, dKDM2 protein plays important roles in regulating circadian rhythms in Drosophila. Further analyses of the molecular mechanisms of dKDM2 and its orthologs in vertebrates regarding the regulation of circadian rhythms will advance our understanding of the epigenetic regulations of circadian clocks

Paternal Origins and Migratory Episodes of Domestic Sheep

The domestication and subsequent global dispersal of livestock are crucial events in human history, but the migratory episodes during the history of livestock remain poorly documented [1-3]. Here, we first developed a set of 493 novel ovine SNPs of the male-specific region of Y chromosome (MSY) by genome mapping. We then conducted a comprehensive genomic analysis of Y chromosome, mitochondrial DNA, and whole-genome sequence variations in a large number of 595 rams representing 118 domestic populations across the world. We detected four different paternal lineages of domestic sheep and resolved, at the global level, their paternal origins and differentiation. In Northern European breeds, several of which have retained primitive traits (e.g., a small body size and short or thin tails), and fat-tailed sheep, we found an overrepresentation of MSY lineages y-HC and y-HB, respectively. Using an approximate Bayesian computation approach, we reconstruct the demographic expansions associated with the segregation of primitive and fat-tailed phenotypes. These results together with archaeological evidence and historical data suggested the first expansion of early domestic hair sheep and the later expansion of fat-tailed sheep occurred ∼11,800-9,000 years BP and ∼5,300-1,700 years BP, respectively. These findings provide important insights into the history of migration and pastoralism of sheep across the Old World, which was associated with different breeding goals during the Neolithic agricultural revolution

Laboratory observation of ion acceleration via reflection off laser-produced magnetized collisionless shocks

Fermi acceleration by collisionless shocks is believed to be the primary mechanism to produce high energy charged particles in the Universe,where charged particles gain energy successively from multiple reflections off the shock front.Here,we present the first direct experimental evidence of ion energization from reflection off a supercritical quasi perpendicular collisionless shock,an essential component of Fermi acceleration in a laser produced magnetized plasma. We observed a quasi monoenergetic ion beam with 2,4 times the shock velocity in the upstream flow using time of flight method. Our related kinetic simulations reproduced the energy gain and showed that these ions were first reflected and then accelerated mainly by the motional electric field associated with the shock. This mechanism can also explain the quasi monoenergetic fast ion component observed in the Earth's bow shock

Proton-Boron Fusion Yield Increased by Orders of Magnitude with Foam Targets

A novel intense beam-driven scheme for high yield of the tri-alpha reaction 11B(p,{\alpha})2{\alpha} was investigated. We used a foam target made of cellulose triacetate (TAC, C_9H_{16}O_8) doped with boron. It was then heated volumetrically by soft X-ray radiation from a laser heated hohlraum and turned into a homogenous, and long living plasma. We employed a picosecond laser pulse to generate a high-intensity energetic proton beam via the well-known Target Normal Sheath Acceleration (TNSA) mechanism. We observed up to 10^{10}/sr {\alpha} particles per laser shot. This constitutes presently the highest yield value normalized to the laser energy on target. The measured fusion yield per proton exceeds the classical expectation of beam-target reactions by up to four orders of magnitude under high proton intensities. This enhancement is attributed to the strong electric fields and nonequilibrium thermonuclear fusion reactions as a result of the new method. Our approach shows opportunities to pursue ignition of aneutronic fusion

Suppression of Allograft Rejection by Tim-1-Fc through Cross-Linking with a Novel Tim-1 Binding Partner on T Cells

Engagement of T-cell immunoglobulin mucin (Tim)-1 on T cells with its ligand, Tim-4, on antigen presenting cells delivers positive costimulatory signals to T cells. However, the molecular mechanisms for Tim-1-mediated regulation of T-cell activation and differentiation are relatively poorly understood. Here we investigated the role of Tim-1 in T-cell responses and allograft rejection using recombinant human Tim-1 extracellular domain and IgG1-Fc fusion proteins (Tim-1-Fc). In vitro assays confirmed that Tim-1-Fc selectively binds to CD4+ effector T cells, but not dendritic cells or natural regulatory T cells (nTregs). Tim-1-Fc was able to inhibit the responses of purified CD4+ T cells that do not express Tim-4 to stimulation by anti-CD3/CD28 mAbs, and this inhibition was associated with reduced AKT and ERK1/2 phosphorylation, but it had no influence on nTregs. Moreover, Tim-1-Fc inhibited the proliferation of CD4+ T cells stimulated by allogeneic dendritic cells. Treatment of recipient mice with Tim-1-Fc significantly prolonged cardiac allograft survival in a fully MHC-mismatched strain combination, which was associated with impaired Th1 response and preserved Th2 and nTregs function. Importantly, the frequency of Foxp3+ cells in splenic CD4+ T cells was increased, thus shifting the balance toward regulators, even though Tim-1-Fc did not induce Foxp3 expression in CD4+CD25− T cells directly. These results indicate that Tim-1-Fc can inhibit T-cell responses through an unknown Tim-1 binding partner on T cells, and it is a promising immunosuppressive agent for preventing allograft rejection