Mitochondrial DNA is a sensitive surrogate and oxidative stress target in oral cancer cells.

Cellular oxidative stress mediated by intrinsic and/or extrinsic reactive oxygen species (ROS) is associated with disease pathogenesis. Oxidative DNA damage can naturally be substituted by mitochondrial DNA (mtDNA), leading to base lesion/strand break formation, copy number changes, and mutations. In this study, we devised a single test for the sensitive quantification of acute mtDNA damage, repair, and copy number changes using supercoiling-sensitive quantitative PCR (ss-qPCR) and examined how oxidative stress-related mtDNA damage responses occur in oral cancer cells. We observed that exogenous hydrogen peroxide (H2O2) induced dynamic mtDNA damage responses, as reflected by early structural DNA damage, followed by DNA repair if damage did not exceed a particular threshold. However, high oxidative stress levels induced persistent mtDNA damage and caused a 5-30-fold depletion in mtDNA copy numbers over late responses. This dramatic depletion was associated with significant growth arrest and apoptosis, suggesting persistent functional consequences. Moreover, oral cancer cells responded differentially to oxidative injury when compared with normal cells, and different ROS species triggered different biological consequences under stress conditions. In conclusion, we developed a new method for the sensitive detection of mtDNA damage and copy number changes, with exogenous H2O2 inducing dynamic mtDNA damage responses associated with functional changes in stressed cancer cells. Finally, our method can help characterize oxidative DNA damage in cancer and other human diseases.

High-Temperature Anomalous Metal States in Iron-Based Interface Superconductors.

The nature of the anomalous metal state has been a major puzzle in condensed matter physics for more than three decades. Here, we report systematic investigation and modulation of the anomalous metal states in high-temperature interface superconductor FeSe films on SrTiO_{3} substrate. Remarkably, under zero magnetic field, the anomalous metal state persists up to 20 K in pristine FeSe films, an exceptionally high temperature standing out from previous observations. In stark contrast, for the FeSe films with nanohole arrays, the characteristic temperature of the anomalous metal state is considerably reduced. We demonstrate that the observed anomalous metal states originate from the quantum tunneling of vortices adjusted by the Ohmic dissipation. Our work offers a perspective for understanding the origin and modulation of the anomalous metal states in two-dimensional bosonic systems.

Quantification of the apical palatal bone index for maxillary incisor immediate implant assessment: A retrospective cross-sectional study.

BACKGROUND: Apical palatal bone is important in immediate implant evaluation. Current consensus gives qualitative suggestions regarding it, limiting its clinical decision-making value. OBJECTIVES: To quantify the apical palatal bone dimension in maxillary incisors and reveal its quantitative correlation with other implant-related hard tissue indices to give practical advice for pre-immediate implant evaluation and design. MATERIAL AND METHODS: A retrospective analysis of immediate implant-related hard tissue indices in maxillary incisors obtained by cone beam computed tomography (CBCT) was conducted. Palatal bone thickness at the apex level (Apical-P) on the sagittal section was selected as a parameter reflecting the apical palatal bone. Its quantitative correlation with other immediate implant-related hard tissue indices was revealed. Clinical advice of pre-immediate implant assessment was given based on the quantitative classification of Apical-P and its other correlated immediate implant-related hard tissue indices. RESULTS: Apical-P positively correlated with cervical palatal bone, whole cervical buccal-palatal bone, sagittal root angle, and basal bone width indices. while negatively correlated with apical buccal bone, cervical buccal bone, and basal bone length indices. Six quantitative categories of Apical-P are proposed. Cases with Apical-P below 4 mm had an insufficient apical bone thickness to accommodate the implant placement, while Apical-P beyond 12 mm should be cautious about the severe implant inclination. Cases with Apical-P of 4-12 mm can generally achieve satisfying immediate implant outcomes via regulating the implant inclination. CONCLUSIONS: Quantification of the apical palatal bone index for maxillary incisor immediate implant assessment can be achieved, providing a quantitative guide for immediate implant placement in the maxillary incisor zone.

The investigation of a portable solar telescope with a high gain metamaterial antenna for F10.7 radio flux measurement.

A high gain and high aperture efficiency metamaterial (MTM) antenna is applied to a solar telescope in this paper. First, a portable solar telescope including the MTM antenna and a receiving system is presented. Next, the theory of the MTM antenna is proposed and analyzed based on the ray-tracing model. The designed MTM antenna is composed of a dual circularly polarized Fabry-Pérot resonant antenna (FPRA) and four phase correction metasurfaces (PCMs). The proposed PCMs act as the reflection surface and the phase correction surface at the same time. Every PCM consists of 2 × 18 optimized artificial magnetic conductor (AMC) units. To solve the parallel incidence and narrow bandwidth problems of AMC units, a nonuniform partially reflective surface is designed. Compared with traditional FPRA, the proposed MTM antenna has an increase in peak gain of 37.5% and an aperture efficiency of 11.4%. Then, a receiving system composed of the receiver, equatorial mount, data acquisition module, and display module is presented for solar radio signal processing. Finally, the designed MTM antenna and solar telescope are simulated and measured. A good agreement between the simulation and measurement is observed and can be used to verify this design.

Functional inference of long non-coding RNAs through exploration of highly conserved regions.

Background: Long non-coding RNAs (lncRNAs), which are generally less functionally characterized or less annotated, evolve more rapidly than mRNAs and substantially possess fewer sequence conservation patterns than protein-coding genes across divergent species. People assume that the functional inference could be conducted on the evolutionarily conserved long non-coding RNAs as they are most likely to be functional. In the past decades, substantial progress has been made in discussions on the evolutionary conservation of non-coding genomic regions from multiple perspectives. However, understanding their conservation and the functions associated with sequence conservation in relation to further corresponding phenotypic variability or disorders still remains incomplete. Results: Accordingly, we determined a highly conserved region (HCR) to verify the sequence conservation among long non-coding RNAs and systematically profiled homologous long non-coding RNA clusters in humans and mice based on the detection of highly conserved regions. Moreover, according to homolog clustering, we explored the potential function inference via highly conserved regions on representative long non-coding RNAs. On lncRNA XACT, we investigated the potential functional competence between XACT and lncRNA XIST by recruiting miRNA-29a, regulating the downstream target genes. In addition, on lncRNA LINC00461, we examined the interaction relationship between LINC00461 and SND1. This interaction or association may be perturbed during the progression of glioma. In addition, we have constructed a website with user-friendly web interfaces for searching, analyzing, and downloading to present the homologous clusters of humans and mice. Conclusion: Collectively, homolog clustering via the highly conserved region definition and detection on long non-coding RNAs, as well as the functional explorations on representative sequences in our research, would provide new evidence for the potential function of long non-coding RNAs. Our results on the remarkable roles of long non-coding RNAs would presumably provide a new theoretical basis and candidate diagnostic indicators for tumors.

Assessment of the inhibition risk of chlorophenol substances on cytochrome P450 via cocktail inhibition assays.

Chlorophenols (CPs) are widespread pollutants in nature. CPs have raised significant concern due to their potential hepatotoxic effects on humans. This research aimed to ascertain the inhibitory potential of eleven CPs (2-CP, 3-CP, 4-CP, 2,4-DCP, 2,3,4-TCP, 2,4,5-TCP, 2,4,6-TCP, 2,3,4,5-TeCP, 2,3,4,6-TeCP, 2,3,5,6-TeCP, and PCP) on nine human CYP isoforms (CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4). The CPs that inhibit the activity of CYP isoforms were detected with human liver microsomes (HLM) using a cocktail approach in vitro. The results demonstrated that trichlorophenols, tetrachlorophenols, and PCP strongly inhibited CYP2C8 and CYP2C9. The half inhibition concentration (IC50) value of 2,3,4,6-TeCP and PCP for CYP2C8 inhibition was 27.3 µM and 12.3 µM, respectively. The IC50 for the inhibition of 2,4,6-TCP, 2,3,4,6-TeCP and PCP towards CYP2C9 were calculated to be 30.3 µM, 5.8 µM and 2.2 µM, respectively. 2,3,4,6-TeCP, and PCP exhibited non-competitive inhibition towards CYP2C8. 2,4,6-TCP, 2,3,4,6-TeCP, and PCP exhibited competitive inhibition towards CYP2C9. The inhibition kinetics parameters (Ki) were 51.51 µM, 22.28 µM, 37.86 µM, 7.27 µM, 0.68 µM for 2,3,4,6-TeCP-CYP2C8, PCP-CYP2C8, 2,4,6-TCP-CYP2C9, 2,3,4,6-TeCP-CYP2C9, PCP-CYP2C9, respectively. This study also defined clear structure-activity relationships (SAR) of CPs on CYP2C8, supported by molecular docking studies. Overall, CPs were found to cause inhibitory effects on CYP isoforms in vitro, and this finding may provide a basis for CPs focused on CYP isoforms inhibition endpoints.

3/2 fractional quantum Hall plateau in confined two-dimensional electron gas.

Even-denominator fractional quantum Hall (FQH) states, such as 5/2 and 7/2, have been well known in a two-dimensional electron gas (2DEG) for decades and are still investigated as candidates of non-Abelian statistics. In this paper, we present the observation of a 3/2 FQH plateau in a single-layer 2DEG with lateral confinement at a bulk filling factor of 5/3. The 3/2 FQH plateau is quantized at [Formula: see text] within 0.02%, and can survive up to 300 mK. This even-denominator FQH plateau may imply intriguing edge structure and excitation in FQH system with lateral confinement. The observations in this work demonstrate that understanding the effect of the lateral confinement on the many-body system is critical in the pursuit of important theoretical proposals involving edge physics, such as the demonstration of non-Abelian statistics and the realization of braiding for fault-tolerant quantum computation.

Ursolic acid prevents doxorubicin-induced cardiac toxicity in mice through eNOS activation and inhibition of eNOS uncoupling.

In addition to the known antitumour effects of ursolic acid (UA), increasing evidence indicates that this molecule plays a role in cardiac protection. In this study, the effects of ursolic acid on the heart in mice treated with doxorubicin (DOX) were assessed. The results showed that ursolic acid improved left ventrical fractional shortening (LVFS) and left ventrical ejection fraction (LVEF) of the heart, increased nitrogen oxide (NO) levels, inhibited reactive oxygen species (ROS) production and decreased cardiac apoptosis in mice treated with doxorubicin. Mechanistically, ursolic acid increased AKT and endothelial nitric-oxide synthase (eNOS) phosphorylation levels, and enhanced eNOS expression, while inhibiting doxorubicin induced eNOS uncoupling through NADPH oxidase 4 (NOX4) down-regulation. These effects of ursolic acid resulted in heart protection from doxorubicin-induced injury. Therefore, ursolic acid may be considered a potential therapeutic agent for doxorubicin-associated cardiac toxicity in clinical practice.

[Human rhinovirus infection promotes mast cell apoptosis and increases the release of inflammatory cytokines].

Objective To investigate the regulation of innate immune response of HMC-1 mast cells to human rhinovirus (HRV) infection. Methods Virus replication in HMC-1 cells was quantified by real-time quantitative PCR (qRT-PCR). Cell viability and apoptosis were assessed by flow cytometry. The levels of tumor necrosis factor α (TNF-α), interferon α (IFN-α), interleukin 6 (IL-6) and IL-8 produced by HMC-1 cells were measured using ELISA. Results After HRV infected HMC-1 cells, the copy numbers of virus RNA and apoptotic cells increased obviously over time, what's more, the release of TNF-α, IFN-α, IL-6 and IL-8 from HMC-1 cells ascended significantly compared with control groups. Conclusion HRV infection can promote mast cell apoptosis and enhance the release of inflammatory cytokines from mast cells.

Inactivation of the ABC transporter ATPase gene in Brucella abortus strain 2308 attenuated the virulence of the bacteria.

Brucella abortus is a Gram-negative, facultative intracellular bacterial pathogen of human and other animals. Brucella lipopolysaccharide has been identified as an important virulence factor. In this study, the ABC transporter ATPase gene (BAB1_0542) of B. abortus strain S2308 was inactivated by deleting a 446-bp fragment from the gene, thereby generating the mutant strain, S2308ΔATP. Real time PCR analysis confirmed the inactivation of this gene with no polar effect on the transcription of adjacent genes on the chromosome. The mutant was identified as a rough phenotype strain using heat agglutination test and crystal violet staining. The mutant strain had a different growth rate in Tryptic Soy Broth (TSB), compared to the wild type S2308 strain. Moreover, the mutant strain showed attenuated virulence in vitro and in vivo in RAW264.7 macrophages and Balb/c mice, respectively. Complementation of the mutant strain recovered the smooth phenotype of the bacteria and the complemented strain C2308ΔATP survived for more than four weeks in Balb/c mice, comparable to wild type strain S2308. Furthermore, immunization with the mutant strain protected mice from virulent strain challenge, which suggests the potential for the mutant strain S2308ΔATP as a future vaccine candidate. MHC I, MHC II and co-stimulatory molecule expression levels in mice following infection of S2308ΔATP and S2308 were also investigated.

Development and evaluation of a trivalent Riemerella anatipestifer-inactivated vaccine.

Riemerella anatipestifer infections cause major economic losses in the duck industry. In this study, a trivalent inactivated vaccine of R. anatipestifer, including strains CH3 (serotype 1), NJ3 (serotype 2), and HXb2 (serotype 10), was developed. Animal experiments showed that the ducks that received two immunizations with the vaccine were 100% protected from challenge with strains from any of the three serotypes (1, 2, or 10). No death or clinical signs of diarrhea, tremors, or limb swelling were shown in the protected ducks. Also, no R. anatipestifer bacteria were isolated from the livers or brains of the protected ducks. Furthermore, no histopathological changes were observed in the liver, spleen, or brain samples from the protected ducks during histological examination. The ducks that received two immunizations with the vaccine generated high antibody titers of 1:3,200 to 1:6,400 against the three serotypes of strains. The vaccine significantly enhanced the production of gamma interferon (IFN-γ) and interleukin 2 (IL-2) after one immunization and enhanced the production of IL-4 and IL-10 after two immunizations. In addition, real-time PCR indicated that the expression of major histocompatibility complex I (MHC-I), as well as that of CD40 and CD154 molecules, was significantly increased after one immunization, and the expressions of both MHC-I and MHC-II molecules were increased after two immunizations. Our study indicates that the vaccine can induce both humoral and cellular immunities in ducks and offer effective protection against R. anatipestifer infection.

Quantum pump effect induced by a linearly polarized microwave in a two-dimensional electron gas.

A quantum pump effect is predicted in an ideal homogeneous two-dimensional electron gas (2DEG) that is normally irradiated by linearly polarized microwaves (MW). Without considering effects from spin-orbital coupling or the magnetic field, it is found that a polarized MW can continuously pump electrons from the longitudinal to the transverse direction, or from the transverse to the longitudinal direction, in the central irradiated region. The large pump current is obtained for both the low frequency limit and the high frequency case. Its magnitude depends on sample properties such as the size of the radiated region, the power and frequency of the MW, etc. Through the calculated results, the pump current should be attributed to the dominant photon-assisted tunneling processes as well as the asymmetry of the electron density of states with respect to the Fermi energy.