Magnon-Skyrmion Hybrid Quantum Systems: Tailoring Interactions via Magnons.

Coherent and dissipative interactions between different quantum systems are essential for the construction of hybrid quantum systems and the investigation of novel quantum phenomena. Here, we propose and analyze a magnon-skyrmion hybrid quantum system, consisting of a micromagnet and nearby magnetic skyrmions. We predict a strong-coupling mechanism between the magnonic mode of the micromagnet and the quantized helicity degree of freedom of the skyrmion. We show that with this hybrid setup it is possible to induce magnon-mediated nonreciprocal interactions and responses between distant skyrmion qubits or between skyrmion qubits and other quantum systems like superconducting qubits. This work provides a quantum platform for the investigation of diverse quantum effects and quantum information processing with magnetic microstructures.

Enhanced Tripartite Interactions in Spin-Magnon-Mechanical Hybrid Systems.

Coherent tripartite interactions among degrees of freedom of completely different nature are instrumental for quantum information and simulation technologies, but they are generally difficult to realize and remain largely unexplored. Here, we predict a tripartite coupling mechanism in a hybrid setup comprising a single nitrogen-vacancy (NV) center and a micromagnet. We propose to realize direct and strong tripartite interactions among single NV spins, magnons, and phonons via modulating the relative motion between the NV center and the micromagnet. Specifically, by introducing a parametric drive (two-phonon drive) to modulate the mechanical motion (such as the center-of-mass motion of a NV spin in diamond trapped in an electrical trap or a levitated micromagnet in a magnetic trap), we can obtain a tunable and strong spin-magnon-phonon coupling at the single quantum level, with up to 2 orders of magnitude enhancement for the tripartite coupling strength. This enables, for example, tripartite entanglement among solid-state spins, magnons, and mechanical motions in quantum spin-magnonics-mechanics with realistic experimental parameters. This protocol can be readily implemented with the well-developed techniques in ion traps or magnetic traps and could pave the way for general applications in quantum simulations and information processing based on directly and strongly coupled tripartite systems.

Progress on the mechanistic research of the trinucleotide repeat instabilities underlying human neurodegenerative diseases.

The expansion and deletion instabilities shown by some trinucleotide repeated DNA sequences are associated with more than 50 neurodegenerative diseases in humans. The increase or decrease of the trinucleotide repeat units underlying the diseases are not yet clearly explained using any mechanism, but has been found to affect the expression of specific genes, or produces cytotoxic RNA and protein, which has now become a common pathological mechanism of the diseases. The ongoing studies have shown that the changes in the copy numbers of the disease-related trinucleotide repeats may result from abnormal DNA replication, repair, recombination, and gene transcription. Human genetical studies also suggest that abnormal DNA replication, repair, recombination, or gene transcription that occurred in the disease-related trinucleotide repeat DNA sites may play a key role in the trinucleotide repeat DNA instabilities. Based on the research experiences of our research group, this paper reviews the recent research progress on the mechanisms of the disease-associated trinucleotide repeat DNA instabilities including their base mutation instabilities, the amplification and deletion instabilities of the repeat units, to better understand the molecular mechanism of the disease-associated trinucleotide repeats instabilities.

Changes in vessel density of the patients with narrow antenior chamber after an acute intraocular pressure elevation observed by OCT angiography.

BACKGROUND: Although the pathogenesis of glaucoma is not fully understood,an elevated intraocular pressure (IOP) is a major factor contributing to its development and progression. The aim of this study was to investigate the changes in the vessel densities of the macula and optic nerve head (ONH) after an acute elevation in the intraocular pressure (IOP) observed using optical coherence tomography angiography (OCTA). METHODS: This was a prospective comparative study of subjects with narrow anterior chamber angles who underwent laser peripheral iridotomies (LPIs). The IOP was measured before and one hour after the LPI. The retinal vessel densities of the macula and ONH were measured using OCTA at the baseline and one hour after the LPI. RESULTS: A total of 64 eyes of 51 individuals were enrolled in this study, and 58 eyes of 43 individuals finally completed the study with a mean IOP rise of 10.5 ± 7.6 mmHg after the LPI. Based on the magnitude of the rise in the IOP, we divided the subjects into three groups: group A = IOP rise ≤10 mmHg, group B = 10 mmHg < IOP rise ≤20 mmHg, and group C = IOP rise > 20 mmHg. The vessel density did not differ after the acute IOP elevation in either the macular region or papillary region in group A or group B (p > 0.05), but there was a significant difference in group C (p < 0.05). However, when the subjects were not separated into groups, the vessel densities of the ONH and macular region did not differ between the measurements obtained at the baseline and one hour after the LPI (p > 0.05). The correlation existed in peripapillary and macular vessel density (p < 0.05). CONCLUSION: In these subjects with narrow antenior chamber, an acute mild or moderate IOP elevation for one hour after the LPI did not affect the vessel density in the macula or ONH, as examined using OCTA. However, when the IOP rise was greater than 20 mmHg, the macular and papillary vessel density decreased significantly.

[SMARCAL1, roles and mechanisms in genome stability maintenance].

SMARCAL1 is an ATP-driven DNA annealing helicase that is similar in structure to the chromatin regulators in the subfamily A group of the SWI/SNF-related matrix-associated actin-dependent chromatin regulators. SMARCAL1 catalyzes the formation of dsDNA by annealing the single-stranded binding protein RPA coated ssDNA with its complementary strand both in vitro and in vivo. In humans, different mutations of Smarcal1 gene are found to be closely related to different symptoms shown in individuals with Schimke immuno-osseous dysplasia (SIOD). This paper reviews the recent research progress of SMARCAL1 functions in remodeling DNA replication forks at damaged DNA sites, working in classical non-homologous end joining (NHEJ) repair of DNA double-stranded breaks, and in maintaining chromosomal telomere integrity. The relationships between the mutations of Smarcal1 gene in different SIOD symptoms, and the possible involvements of SMARCAL1 in neuromuscular degenerative diseases associated with trinucleotide repeats expansions are also updated and discussed to better understand the roles and mechanisms of the annealing helicase in genome stability maintenance.

[Distribution and evolution of simple repeats in the mtDNA D-loop in mammalian].

Simple sequence repeats (SSR) distribute extensively in genomes of all organisms, but the molecular mechanism underlined is poorly understood. In this study, we characterized distribution and biological significance of the simple repetitive DNA sequences in the D-loop region in mitochondria DNA of 256 mammal species, and classified the mammal carriers into three groups including 53 species with hexanucleotide repeats, 104 species with other types of simple repeats (>6 bp) and 99 species without any repeat sequences, respectively. Furthermore, we found that the hexanucleotide repeats dispersed significantly in the interval space between CSB1 and CSB2, while other repeats dispersed mainly in the termination region, central conserved region and the conserve sequence block (CSB) regions. In addition, comparison on the base composition and the DNA contexts of the central conserved region, CSB1, CSB2, and CSB3 revealed a lack of significant differences in similarity among different species with or without repeat sequences. Moreover, a phylogenetic analysis with 256 mammal species using N-J method suggested loss of the repeat sequences in mammals in evolution.

Inhibition of endothelin-1 and hypoxia-induced pulmonary pressor responses in the rat by a novel selective endothelin-A receptor antagonist, di-n-butylaminocarbamyl-L-leucyl-D-tryptophanyl-D-4-chloro-Phe.

Pulmonary hypertension is a kind of disease associated with a very high rate of mortality, and there are not many effective drugs for the treatment. Today, endothelin (ET)-1 receptor antagonists were proved to be effective in the treatment of pulmonary hypertension. Aiming at developing new endothelin-A receptor (ETA) antagonist for treatment of pulmonary hypertension, di-n-butylaminocarbamyl-L-leucyl-D-tryptophanyl-D-4-chloro-Phe, named GF063, was synthesized at base of selective ETA receptor antagonist BQ485 and selected for the further pharmacological characterization. The preliminary pharmacodynamics of GF063 was evaluated by radioligand receptor binding assay and test of antivasoconstriction effects in vitro and in vivo. The integrative pharmacodynamics was evaluated in hypoxia-induced rat pulmonary hypertension. In vitro, GF063 bound to ETA receptor with 100,000-fold higher affinity than to ETB receptor. GF063 concentration dependently inhibited contraction of isolated rat aortic ring induced by ET-1 and shifted the cumulative concentration-contraction response curve to right with no change in the maximal response. In vivo, GF063 inhibited the increase of mean systemic arterial pressure induced by ET-1 in anesthetized rat. In hypoxia-induced rat pulmonary hypertension model, pretreatment with GF063 (40 mg/kg, s.c.) significantly decreased pulmonary artery pressure and right ventricular hypertrophy, also significantly inhibited the increase of ET-1 level in lung, improved hemodynamics, and alleviated the wall thickness of pulmonary vessels. This study indicated that GF063, as a selective ETA receptor antagonist, could inhibit vasoconstriction effects in vivo and in vitro, could prevent pulmonary hypertension induced by hypoxia, and may have great potential to be developed as a new drug of antipulmonary hypertension.

Gene Expressions Underlying Mishandled Calcium Clearance and Elevated Generation of Reactive Oxygen Species in the Coronary Artery Smooth Muscle Cells of Chronic Heart Failure Rats.

BACKGROUND: The calcium clearance and reactive oxygen species (ROS) generations in the coronary artery smooth muscle cells in chronic heart failure (HF) have not been fully investigated. Therefore, we attempted to understand the gene expressions underlying the mishandling of calcium clearance and the accumulations of ROS. METHODS: We initially established an animal model of chronic HF by making the left anterior descending coronary artery ligation (CAL) in rats, and then isolated the coronary artery vascular smooth muscle cells from the ischemic and the nonischemic parts of the coronary artery vessels in 12 weeks after CAL operation. The intracellular calcium concentration and ROS level were measured using flow cytometry, and the gene expressions of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a), encoding sarcoplasmic reticulum Ca2+-ATPase 2a, encoding sodium-calcium exchanger (NCX), and p47phox encoding a subunit of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase were examined using real-time quantitative reverse transcription polymerase chain reaction and Western blotting, respectively. RESULTS: We found that the calcium accumulation and ROS generation in the coronary artery smooth muscle cells isolated from either the ischemic or the nonischemic part of the CAL coronary artery vessel were significantly increased irrespective of blood supply (all P < 0.01). Moreover, these were accompanied by the increased expressions of NCX and p47phox, the decreased expression of SERCA2a, and the increased amount of phosphorylated forms of p47phox in NADPH oxidase (all P < 0.05). CONCLUSIONS: Our results demonstrated that the disordered calcium clearance and the increased ROS generation occurred in the coronary artery smooth muscle cells in rats with chronic HF produced by ligation of the left anterior descending coronary artery (CAL), and which was found to be disassociated from blood supply, and the increased generation of ROS in the cells was found to make concomitancy to the increased activity of NADPH oxidase in cytoplasm.

Effects of degU32(Hy), degQa and degR pleiotropic regulatory genes on the growth and protease fermentation of Bacillus subtilis Ki-2-132.

Effects of degU32 (Hy), degR genes from Bacillus subtilis 168 and degQa gene from Bacillus amyloliquefaciens on Bacillus subtilis Ki-2-132 cell growth, sporulation and protease fermentation were investigated by introducing these genes into B. subtilis Ki-2-132 chromosome and/or cytoplasm. Although the genes come from different species and strains, they showed pleiotropic effects in B. subtilis Ki-2-132. B. subtilis Ki-2-132degU32 (Hy) showed increased protease production, and when cooperating with degQa either in plasmid or in chromosome, further altered cell growth, increased protease production and affected the spore formation in a glucose and dosage dependent manner. By contrast, degR did not significantly affect the protease productivity in degU32 (Hy) mutant, consisting with that DegR was used to stabilise DegU-phosphate, which in degU32 (Hy) strain no longer further amplify the DegU-phosphate effect.

Mechanism of trinucleotide repeats instabilities: the necessities of repeat non-B secondary structure formation and the roles of cellular trans-acting factors.

The mechanism underlying CAG.CTG CGG.CCG and GAA.TTC trinucleotide repeats expansion and contraction instabilities has not been clearly understood. Investigations in vitro have demonstrated that the disease causing repeats are capable of adopting non-B secondary structures that mediate repeats expansion. However, in vivo, similar observations have not been easily made so far. Investigations on the non-B secondary structure formation using E.coli, yeast etc cannot simulate the suggested repeats expansion instability. These could leave a space to infer a disassociation of the suggested repeats non-B secondary structure formation and the repeats expansion in vivo. Although longer trinucleotide repeats may be theoretically easier to form non-B DNA secondary structures in replication or in post-replication, however such non-B secondary structures are likely to cause repeat fragility rather than repeat expansion. In fact, repeat expansion as seen in patients may not necessarily require trinucleotide repeats to form non-B secondary structures, instead the repeat expansions can be produced through a RNA transcription-stimulated local repeat DNA replication and a subsequent DNA rearrangement.

Staged bilateral single-port thoracoscopic lung volume reduction surgery: A report of 11 cases.

The aim of the present study was to investigate the feasibility and efficacy of staged bilateral single-port thoracoscopic lung volume reduction surgery (LVRS) for patients with chronic obstructive pulmonary emphysema (COPE). Eleven male patients with a mean age of 60.27±12.11 years with bilateral COPE and bullae were admitted to the Department of Thoracic Surgery, Xuzhou Central Hospital from January 2013 to June 2014. The patients underwent staged bilateral single-port thoracoscopic LVRS. The hyperinflated bullae were resected using endoscopic staplers (Endo-GIA), followed by continuous suture and biological glue for reinforcement of the margin. In addition, pulmonary function, blood gas assay, 6-min walk distance (6MWD) and life quality evaluated by a short form 36-item health survey questionnaire (SF-36) were recorded before and after LVRS, respectively. All the patients survived after surgery. The chest tube drainage time was 9.09±1.31 days and postoperative hospital stay was 15.73±2.75 days, with 5 cases of persistent air leakage and 7 cases of pulmonary infection which were finally cured. The patients were followed up for 3 to 12 months, and the pulmonary function, partial pressure of oxygen (pO2), 6MWD and life quality after unilateral or bilateral LVRS were improved compared to these parameters before surgery. However, there was no significant difference between unilateral and bilateral LVRS in terms of life quality. In conclusion, staged bilateral single-port thoracoscopic LVRS may improve the short-term life quality of patients with COPE.

[Influence of Cryopreservation on Human Peripheral Blood Mononuclear Cell Immunocompetence].

OBJECTIVE: To establish a method for isolation, cryopreservation and recovery of the highly viable human peripheral blood monomuclear cells (PBMNCs) so as to achieve the long-term preservation of PBMNCs. METHODS: A total of 80-100 ml peripheral blood were collected from the healthy volumteers aged over 50 years old. The PBMNCs were isolated by the Ficoll density gradient technique and cryopreserved gradually by program control method in liquid nitrogen freezer of -196 °C. The serum-free medium and autoloqous plasma medium were test for preservation of PBMNCs. The cell viability was assessed at time point of 1, 2, 4, 8, 12 and 24 months after thawing. Finally, the proliferation ability, purity and cytotoxicity were compared between the autologous immune lymphocytes (AIL) induced from cryopreserved PBMNCs and AIL as control from fresh PBMNCs. RESULTS: After separating, the cell viability was 99.6%±0.4%, and the recovery rate of lymphocytes was 58.4%±6.52%. The cell recovery rate of lymphocyte was 89.7%±3.82% at 24 months. The quality assurance program was reliable within 2 years of running. The AIL cells induced with cryopreserved PBMNCs were not significantly different from those induced from fresh PBMNCs in terms of proliferative action, purity and cytotoxicity(CD3(+)CD8(+) ≥45%,CD3(+)CD56(+) NKT≥10%,CD4(+)CD25(+) NKT≤10%). CONCLUSION: Manual separation of lymphocytes in vitro can get enough high-quality PBMNCs. The long-term cryopreserved PBMNC still maintain their high viability. The reinfusion of the clinical autologous immune cells would be advantageous for early tumor immunotherapy. Human AIL induced from cryopreserved PBMNC maintain their anti-tumor ability. These findings have the important implications for the application of these cells to adoptive cellular therapy.