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To obtain the influence of anisotropy and energy evolution characteristics on wellbore stability, the acoustic and mechanical anisotropy characteristics of shales are studied through various experiments, including scanning electron microscopy, ultrasonic pulse transmission, and uniaxial compression experiments, with the Longmaxi Formation shale in the southern area of the Sichuan Basin as the research object. The energy evolution characteristics of the Longmaxi Formation shale under different bedding angles are analyzed. The influence of anisotropy on the wellbore stability of shale formation is discussed on this basis. The results show that the acoustic and mechanical parameters, failure mode, and energy evolution characteristics of shale have significant anisotropy. Furthermore, the P-wave and S-wave time differences decrease with an increase in bedding angle. The compressive strength and Poisson's ratio decrease first and then increase with an increase in bedding angle. Meanwhile, the elastic modulus gradually increases with an increase in bedding angle. Rock samples with different bedding angles show diverse failure modes in mechanical tests, including splitting, shear, and shear-splitting failure. The total energy and elastic energy decrease first and then increase with an increase in bedding angle. Finally, the formation anisotropy affects the wellbore stability: the higher the formation anisotropy, the more vulnerable is the wellbore to instability. [ABSTRACT FROM AUTHOR]

Juvenile-onset recurrent respiratory papillomatosis (JORRP) is caused by persistent infection of epithelial cells by low-risk human papillomavirus (HPV) types 6 and 11. While multiple infiltrated immune cells have been reported to mediate disease progress, knowledge of HPV-reactive T-cell subsets in papillomas remains elusive. Through single-cell RNA sequencing and RNA microarray, we found that CD8+ tissueresident memory T (CD8+ TRM) cells with strong interferon-gamma (IFN-γ) production expanded, and were negatively correlated to the disease severity in the frequency of surgery. These IFN-γ+ CD8+ memory T cells were readily activated and expanded in vitro by autologous dendritic cells loaded with HPV11 E7 peptide pool. Moreover, T cell receptor (TCR) clonal expansion was observed in JORRP papilloma tissues, indicating a biased TCR repertoire toward HPV-specific recognition. Finally, we identified and characterized HPV11 E7-specific candidate TCR clonotypes from IFN-γ+ CD8+ memory T cells, suggesting their potential application in TCR-engineered T cells (TCR-T) therapy for HPV11-related diseases. Our findings provided insights into the specific local immune response to HPV6/11 infection and highlighted the importance of IFN-γ+ CD8+ TRM cells in anti-HPV6/11 T-cell immunity. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the prevalence of clinical mcr-1-positive Escherichia coli and Klebsiella pneumoniae and characterize the antimicrobial resistance profiles of mcr-1-positive E. coli and mcr-1-negative E. coli in China.Methods: A total of 6264 clinical E. coli (n = 3854) and K. pneumoniae (n = 2410) were collected from hospitalized patients from 18 to 20 hospitals as part of the China Antimicrobial Resistance Surveillance Trial (CARST) between January 2007 and June 2016. PCR was used to screen for the mcr-1 gene among all isolates. Antibiotic susceptibility testing was performed using the broth microdilution method. mcr-1-positive pathogens were then characterized by MLST and minimum spanning tree analysis using the BURST algorithm for related STs.Results: We examined 39 (0.62%) clinical isolates of mcr-1-positive E. coli and K. pneumoniae over a 10 year period. Resistance to antimicrobial agents was significantly more severe in mcr-1-positive isolates than mcr-1-negative isolates, particularly piperacillin (P = 0.008), amikacin (P < 0.0001), nitrofurantoin (P < 0.004) and fosfomycin (P < 0.0001). Among mcr-1-carrying isolates, ESBL production was as high as 84.6% (33 of 39) and 92.3% (36 of 39) of them displayed an MDR phenotype. STs suggested ubiquitous dissemination of mcr-1-carrying pathogens.Conclusions: mcr-1-carrying E. coli and K. pneumoniae displayed a lower prevalence and abundant phylogenetic diversity in mainland China. mcr-1-positive E. coli showed significant differences in antimicrobial resistance profiles compared with mcr-1-negative E. coli strains, suggesting physicians may consider prescribing different antibiotics when faced with infections caused by mcr-1-positive pathogens. [ABSTRACT FROM AUTHOR]

Low thermal conductance across interface is often the limiting factor in managing heat in many advanced device applications. The most commonly used approach to enhance the thermal conductance is to reduce/eliminate the interfacial structural defects. Using a graphene/h-BN (Gr/h-BN) interface, we show surprisingly that topological defects are able to enhance the thermal conductance across the interface. It is found that the phonon transmission across the Gr/h-BN interface with 5|7 defects is higher than that of the pristine interface, which is in strong contrast to the common notion that interface defects promote phonon scattering. By analyzing the strain distribution and phonon vibrational spectra, we find that this abnormal enhancement in interfacial thermal conductance originates from the localization of the stress fields arising from misfit dislocations and their out-of-plane deformations at the interface. In the presence of the defects, the overall mismatch strain is reduced. In addition, the out-of-plane deformations screen the long-ranged dislocation strain fields, resulting in the stress fields to be localized only at the cores of the defects. This abnormal mechanism provides a new dimension to enhance the interfacial thermal conductance in two-dimensional heterostructures. [ABSTRACT FROM AUTHOR]

Acid fracturing has been widely used to increase oil and gas well productivity. However, the wormholes, emerging when fracturing, have a great effect on the deliverability of a gas well. Based on the influences of the real gas PVT variation on the well deliverability under formation conditions and the non-Darcy effects, a productivity prediction model of a finite conductivity vertical acid fracturing well in a low-permeability reservoir was established, considering the slippage effect, threshold pressure gradient, and stress sensitivity. The result shows that the gas well productivity with variation of the gas PVT parameters is higher than that with constant PVT parameters during the low-flowing bottom hole pressure. The variation of PVT parameters has a larger impact on the gas well productivity, which decreases with the increase of the threshold pressure gradient and the stress sensitivity coefficient and increases with the increase of the slippage factor. In the fracture design of the low-permeability gas reservoir, it is more important to increase fracture length than its conductivity. There is an optimum value of flow conductivity that exists under a certain fracture length, which increases with the increase of the fracture length. In addition, the wormhole length and permeability of the wormhole area have different impacts on the gas well productivity, and their mechanisms are different. The longer wormhole length has a negative impact on the gas production, whereas the permeability of the wormhole zone has a positive influence. [ABSTRACT FROM AUTHOR]

A simple and effective strategy for designing ratiometric fluorescent nanosensor has been described in this work. A carbon dots (CDs) based dual-emission nanosensor for Cu2+ detection was prepared by coating CDs on the surface of Rhodamine B-doped silica nanoparticles. The fluorescent CDs were synthesized using N-(β-aminoethyl)-γ-aminopropyl methyldimethoxysilane (AEAPMS) as the main raw material, so that the residual ethylenediamine groups and methoxysilane groups on the surface of CDs can serve as the Cu2+ recognition sites and the silylation reaction groups. The obtained nanosensor showed characteristic fluorescence emissions of Rhodamine B (red) and CDs (blue) under a single excitation wavelength. Upon binding to Cu2+, only the fluorescence of CDs was quenched, resulting in the ratiometric fluorescence response of the dual-emission silica nanoparticles. This ratiometric nanosensor exhibited good selectivity to Cu2+ over other substances, such as metal ions, amino acids, proteins, and vitamin C. The ratio of F467/F585 linearly decreased with the increasing of Cu2+ concentration in the range of 0 to 3 × 10–6 M, a detection limit as low as 35.2 nM was achieved. Additionally, this nanosensor was successfully applied for the ratiometric fluorescence imaging of Cu2+ in cells and determination of Cu2+ in real tap water. [ABSTRACT FROM AUTHOR]

DNA sequences with repetitive G-rich structural motifs, which form special structures called G-quadruplexes, widely exist in the human genome. Here we report the general peroxidase activity of G-quadruplex-hemin complexes and discuss the connection between peroxidase activity and G-quadruplex structures. The high peroxidase activity of hemin complexed with intramolecular parallel G-quadruplex- forming sequences in gene promoters (such as c-Myc, VEGF, c-Kit21, HIF-1α, and RET) may imply a potential mechanism of hemin-mediated cellular injury. This peroxidase activity has also been demonstrated to be applicable for screening G-quadruplex ligands (potential anticancer reagents) using colorimetric and visual detection strategies. [ABSTRACT FROM AUTHOR]

Here we describe a highly selective and reversible Hg2+ sensor, tetra-(thymin-1-yl-acetamido)-phthalocyanine Zn(II) (4T-ZnPc), which combined the optical properties of phthalocyanine (Pc) and the specific interaction of Hg2+ with thymine (T). The novel phthalocyanine-nucleobase conjugate, 4T-ZnPc, shows a typical ultraviolet—visible absorption spectrum with a split Q-band of monomeric Pc in diinethylformamide (DMF)—water (7:3, v/v) solution, as well as strong fluorescence emission. Upon addition of Hg2+, the formation of T—Hg—T complex induces aggregation of 4T-ZnPc and results in significant decreases of fluorescence intensity and absorption of the Q-band. Furthermore, the sensor molecules, 4T-ZnPc, show excellent selectivity for Hg2+, and other ions, such as Pb2+, Co2+, Ni2+, Zn2+, Cd2+, Mn2+, Mg2+, Ca2+, Na+, and K+, have almost no effect on the optical properties of 4T-ZnPc. This kind of sensor based on Pc may be expanded to the detection of other targets by substituting thymines with other ligands or groups that possess molecular recognition ability. [ABSTRACT FROM AUTHOR]

In recent years, significant advancements have been achieved in the exploration of natural gas around Shawan Sag in the Junggar Basin. However, the geochemical characteristics and distribution of source rocks in the center of the sag have yet to be thoroughly researched, and there is a lack of understanding regarding the evolution history of hydrocarbon generation and the characteristics of each set of source rocks. This has posed limitations on future exploration and development initiatives in the area. The study focused on source rock samples from the uplift zone and conducted a comprehensive evaluation through seismic and hydrocarbon generation thermal simulation experiments. This allowed for clarification of the product characteristics of source rocks in different strata and pointing out the direction for future natural gas exploration. The results showed the presence of four sets of well-developed source rocks in Shawan Sag, characterized by their extensive thickness, wide distribution, and deep burial, laying a material foundation for oil and gas accumulation in peripheral structures. The Carboniferous and Jiamuhe Formation source rocks have high organic matter abundance, but the quality is poor and the potential for generating hydrocarbons is low, leading mainly to the generation of dry gas. On the other hand, the Fengcheng Formation and Lower Wuerhe Formation source rocks have high organic matter abundance and good quality, and are highly mature, resulting in high potential for generating hydrocarbons. The δ13C1-RO regression equation of natural gas in Shawan Sag was established, and the carbon isotope distribution patterns of ethane generated from source rocks in different layers were identified, providing a foundation for determining the maturity of natural gas and correlating the sources of gas in surrounding structures. The west slope of Shawan Sag has favorable preservation conditions and is located on a hydrocarbon migration pathway, similar to the slope of Mahu Sag. This area also has favorable geological conditions for the formation of large lithologic reservoirs, making it a key field for gas exploration in the study area moving forward. [ABSTRACT FROM AUTHOR]

Loess sequences of the Chinese Loess Plateau (CLP) compose one of the most complete Neogene-Quaternary terrestrial paleoclimatic archives. Understanding the CLP's sediment sources is critical to tracing Asian aridification, atmospheric circulation patterns, and Asian monsoon evolution. Commonly, the sediments that compose the Quaternary strata of the CLP are considered largely homogeneous, and thus numerous studies have applied a uniform source model when attempting to use CLP-derived proxies as paleoclimate indicators. Here we present large-n detrital zircon U-Pb geochronology data from the Quaternary CLP. These data support spatial variability in sediment provenance across the CLP. At least three distinct provenance zones are recognized for Quaternary loess strata: central western, eastern, and northeastern. These zones received sediment primarily from their neighboring river systems. This finding conflicts with the classic views that attribute the Quaternary loess principally to the deserts north and west of the CLP. We conclude that fluvial processes, and thus precipitation, played an important and previously underemphasized role in Quaternary dust production in northern China. Furthermore, nonuniformity in CLP Quaternary sediment provenance raises questions about the validity of using paleoclimate information archived in the CLP to make sweeping regional interpretations. [ABSTRACT FROM AUTHOR]

Beyond graphene, the layered transition metal dichalcogenides (TMDs) have gained considerable attention due to their unique properties. Herein, we review the lattice dynamic and thermal properties of monolayer TMDs, including their phonon dispersion, relaxation time, mean free path (MFP), and thermal conductivities. In particular, the experimental and theoretical studies reveal that the TMDs have relatively low thermal conductivities due to the short phonon group velocity and MFP, which poses a significant challenge for efficient thermal management of TMDs-based devices. Importantly, recent studies have shown that this issue could be largely addressed by connecting TMDs and other materials (such as metal electrode and graphene) with chemical bonds, and a relatively high interfacial thermal conductance (ITC) could be achieved at the covalent bonded interface. The ITC of MoS2/Au interface with chemical edge contact is more than 10 times higher than that with physical side contact. In this article, we review recent advances in the study of TMD-related ITC. The effects of temperature, interfacial vacancy, contact orientation, and phonon modes on the edge-contacted interface are briefly discussed. [ABSTRACT FROM AUTHOR]

In this work, the adsorption behaviors of CH4 in slit-like kaolinite pores were investigated using the grand canonical Monte Carlo method. The research results show that the isosteric heat of adsorption of CH4 decreases with increasing pore size and that CH4 adsorption on kaolinite can be characterized as physical adsorption. The potential energy between CH4 and kaolinite was found to decrease with increasing pressure or decreasing pore size, indicating that the adsorption sites of CH4 changed from higher-energy adsorption sites to lower-energy adsorption sites. The CH4 adsorption capacity decreased with increasing pore size in mesopores. With increasing temperature, the isosteric heat of adsorption of CH4 decreased, and the adsorption sites of CH4 changed from higher-energy adsorption sites to lower-energy adsorption sites, resulting in a decrease of the CH4 adsorption capacity. As a result of van der Waals force interactions, Coulomb force interactions, and hydrogen-bonding interactions, the water molecules in the kaolinite pores occupies the pore walls in a directional manner, causing the water molecules in the kaolinite pores to accumulate. With increasing accumulation of water, the water molecules occupied adsorption spaces and adsorption sites of CH4, leading to a decrease of the CH4 adsorption capacity. The gas adsorption capacity on kaolinite was found to decrease in the following order: CO2 > CH4 > N2. With increasing mole fraction of N2 or CO2, the mole fraction of CH4 in the gas phase decreased, the adsorption sites of CH4 changed, and the adsorption space of CH4 decreased, resulting in a decrease of CH4 adsorption capacity. [ABSTRACT FROM AUTHOR]

Hydraulic fracturing is an efficient stimulation technology in the process of unconventional reservoir development, and the hydraulic fracture morphology directly affected oil and gas recovery. In this paper, we proposed a new criterion based on linear elastic fracture mechanics (LEFM) to predict the intersection behavior of hydraulic fracture (HF) and natural fracture (NF) with non-orthogonal angle. The new criterion considered the coupling effects of the fluid flow, stress shadow, and poroelastic response, and was validated with published analytical criteria and laboratory tests. Sensitivity analysis results indicated that an HF tends to cross NF under conditions of short HF half-length, high friction coefficient, high fracturing fluid viscosity and high fracture toughness. In addition, high principal stress difference inhibited the crossing behavior when the intersection angle was less than the transition angle, the HF would be arrested or divert along NF. [ABSTRACT FROM AUTHOR]

In order to investigate the adsorption capacity of CHA on the different types of kerogen, the paper used the thermo-dynamic theory and improved Dubinin-Astakhov (D-A) equation [Dubinin and Astakhov, Bull. Acad. Sci. USSR, Div. Chem. Sci, vol. 20, no. 1, pp. 3-7,1971] to build calculation models of the isosteric heat of adsorption. Based on adsorption isothermal experiments, the study object of this work is the different types of kerogen. Then the variation law of isosteric heat of adsorption of CH4 on the different types of kerogen was investigated. The results show that by combining the D-A adsorption model with the adsorption characteristic curve, the improved D-A adsorption model was deduced. The improved D-A adsorption model fits well with the adsorption data, and the average relative error is less than 4.42%. The initial isosteric heat of adsorption reflects the intermolecular force between CHA and kerogen, which increased with increasing the adsorption volume, which reflects the energetically heterogeneous surface of different types of kerogen. The intermolecular force between CH4 and kerogen from large to small in order was type III, type II, type I, which may be related to the chemical construction of different types of kerogen. [ABSTRACT FROM AUTHOR]

Laryngopharynx epithelium neoplasia induced by HPV6/11 infection in juvenile-onset recurrent respiratory papillomatosis (JO-RRP) causes a great health issue characteristic of frequent relapse and aggressive disease progression. Local cell-mediated immunity shaped by the recruitment and activation of cytotoxic effector cells is critical for viral clearance. In this study, we found that NK cells in the papillomas of aggressive JO-RRP patients, in contrast to massive infiltrated T cells, were scarce in number and impaired in activation and cytotoxicity as they were in peripheral blood. Data from cell infiltration analysis indicated that the migration of NK cell to papilloma was restricted in aggressive JO-RRP patients. Further study showed that the skewed chemokine expression in the papillomas and elevated ICAM-1 expression in hyperplastic epithelia cells favored the T cell but not NK cell recruitment in aggressive JO-RRP patients. In parallel to the increased CD31 T cells, we observed a dramatical increase in Tregs and Treg-promoting cytokines such as IL-4, IL-10 and TGFb in papillomas of aggressive JO-RRP patients. Our study suggested that likely initialized by the intrinsic change in neoplastic epithelial cells with persistent HPV infection, the aggressive papillomas built an entry barrier for NK cell infiltration and formed an immunosuppressive clump to fend off the immune attack from intra-papillomas NK cells. IMPORTANCE Frequent relapse and aggressive disease progression of juvenile-onset recurrent respiratory papillomatosis (JO-RRP) pose a great challenge to the complete remission of HPV 6/11 related laryngeal neoplasia. Local immune responses in papillomas are more relevant to the disease control considering the locale infected restriction of HPV virus in epitheliums. In our study, the restricted NK cell number and reduced expression of activating NKp30 receptor suggested one possible mechanism underlying impaired NK cell defense ability in aggressive JO-RRP papillomas. Meanwhile, the negative impact of HPV persistent infection on NK cell number and function represented yet another example of a chronic pathogen subverting NK cell behavior, affirming a potentially important role for NK cells in viral containment. Further, the skewed chemokine/cytokine expression in the papillomas and the elevated adhesion molecules expression in hyperplastic epithelia cells provided important clues for understanding blocked infiltration and antiviral dysfunction of NK cells in papilloma. [ABSTRACT FROM AUTHOR]

In this paper, the mechanical behaviors of different lithological rocks of coal measure strata from Shanxi Formation in the eastern margin of the Ordos Basin, China, were investigated through uniaxial compression tests, and the deformation characteristics and failure modes of different lithological rocks were investigated. On this basis, the energy evolution of different lithology rocks was also discussed. The results show that there are obvious differences in the mechanical properties of different lithology rocks in coal measure strata, resulting in different wellbore instability prevention measures and fracturing measures in different lithology strata. Under the uniaxial compression condition, the peak strain of different lithological rocks is obviously different, and the denaturation characteristics are also obviously different, and the failure modes of rocks are mainly the tensile fracture mode, suggesting that the rock samples have strong brittle characteristics. With the increase of the strain, the total energy of different lithological rocks of the coal measure strata increases, and the elastic energy first increases and then decreases rapidly, whereas the dissipated energy first increases slowly and then increases rapidly. Each energy at the peak point is different, and the average total energy of shale, silty shale, siltstone, fine sandstone, and coal is 0.022 J/cm3, 0.045 J/cm3, 0.052 J/cm3, 0.042 J/cm3, and 0.003 J/cm3, respectively, indicating that there are obvious differences in the energy evolution laws of the different lithological rocks. [ABSTRACT FROM AUTHOR]

Using 1,981 pieces of temperature records extracted from a selection of tree rings, ice cores, sediments, and other materials with high-resolution historical temperature proxy data, a temperature series of the past 2,000 years on the Tibetan Plateau (TP) with 10-year intervals was reconstructed by the method of single sample correction-multi-sample average integration equations. This series shows that the warm periods mainly appeared before 235 A.D., 775-1275 A.D. and 1845-2000 A.D., while the cold periods occurred 245-765 A.D., 1045-1145 A.D., and 1285-1835 A.D. The Little Ice Age left clear evidence on the TP and its coldest period was between 1635 and 1675 A.D. The Medieval Warm Period on the TP was not as warm as that in the late twentieth century. During the nineteenth century, overall temperature tends to be warmer with a clear rising trend, and in the late twentieth century new highs broke the record of the past 2,000 years. Power spectrum analysis shows that temperature on the TP changes consistently and evidently in a 150-year cycle. This integrated series also shows clear correlations with sunspot activity and solar radiation, as high sunspot activities generally led to warmer periods, and vice versa. Solar activities and intense radiation of recent years are naturally conducive to the global warming since the nineteenth century. The combination of greenhouse gases and natural fluctuations in climate has been the main culprit behind the global warming in the twentieth century. [ABSTRACT FROM AUTHOR]

Motivation: The highly coordinated expression of thousands of genes in an organism is regulated by the concerted action of transcription factors, chromatin proteins and epigenetic mechanisms. High-throughput experimental data for genome wide in vivo protein–DNA interactions and epigenetic marks are becoming available from large projects, such as the model organism ENCyclopedia Of DNA Elements (modENCODE) and from individual labs. Dissemination and visualization of these datasets in an explorable form is an important challenge. [ABSTRACT FROM PUBLISHER]

Cutaneous T cell lymphoma is a generally indolent disease derived from skin-homing mature T cells. However, in advanced stages, cutaneous T cell lymphoma may manifest aggressive clinical behaviour and lead to a poor prognosis. The mechanism of disease progression in cutaneous T cell lymphoma remains unknown. This study, based on a large clinical cohort, found that IKZF2, an essential transcription factor during T cell development and differentiation, showed stagedependent overexpression in the malignant T cells in mycosis fungoides lesions. IKZF2 is specifically overexpressed in advanced-stage mycosis fungoides lesions, and correlates with poor prognosis. Mechanistically, overexpression of IKZF2 promotes cutaneous T cell lymphoma progression via inhibiting malignant cell apoptosis and may contribute to tumour immune escape by downregulating major histocompatibility complex II molecules and up-regulating the production of anti-inflammatory cytokine interleukin-10 by malignant T cells. These results demonstrate the important role of IKZF2 in high-risk cutaneous T cell lymphoma and pave the way for future targeted therapy. [ABSTRACT FROM AUTHOR]

Salix matsudana Koidz was exposed to different concentrations of Cd (0, 10, 50, and 100 μmol/L) to study the effects of Cd on mineral metabolism and antioxidant enzyme activities. The results showed that plant height and root length were inhibited by 50 and 100 μmol/L Cd, except the one under 10 μmol/L Cd treatment. The Cd content accumulated in different organs of S. matsudana, gradually increasing with increased Cd concentrations and prolonged treatment times. The root was the main organ for absorbing and accumulating Cd. Cd inhibited the accumulation of Fe, Zn, Mn, and Cu. In addition, the activities of antioxidant enzymes and the contents of reactive oxygen species were also changed by different concentrations of Cd. The results obtained here can provide scientific and objective data for the use of S. matsudana in the remediation of Cd-contaminated soil. [ABSTRACT FROM AUTHOR]

Provenance of the silt on the Chinese Loess Plateau (CLP) is essential for the paleo-environmental interpretation of the thick eolian deposits, but is highly debated. The controversy mainly comes from the multi-interpretation of similar geochemical signatures of potential source areas (PSAs). This work applies the (234U/238U) activity ratio as a new source tracer, because it can distinguish particles with different transporting and recycling histories regardless of petrological origin. The (234U/238U) activity ratio of a fine particle decreases progressively after its production because of the increasing fraction of the 234U precursor ejected out of the particle surface, due to the recoiling effect associated with the α decay of 238U. Distinct spatial patterns of (234U/238U) can be found for the sediments in PSAs and the loess on the CLP. When combined with other constraints, the new findings indicate that the CLP loess can be best explained by the mixing of three end-member dust sources on the northwestern transportation trajectory, namely (1) the Gobi Desert, (2) the Ordos Desert, and (3) the Qilian Mountains. A contribution from the Yellow River is also possible but may not be significant. The identified source partition implies that the eolian silt is mainly produced by processes in the 'High Asia' mountains and, partly, by erosion of the exposed clastic rocks. This new constraint on the production and transportation of eolian dust has great implications for the proxy interpretation of loess related to atmospheric circulation, dust accumulation rate, and chemical indexes. [ABSTRACT FROM AUTHOR]

Luminescence dating is a useful chronological tool for glaciogenic sediments, especially when the targeted sediments lack organic materials or are too old for radiocarbon dating. However, problems like partial bleaching make its application on glaciogenic sediments challenging. Poor luminescence characteristics and low saturation level of quartz limit its application in glacial environments, especially dating old glacial sediments. Developments of the single-grain technique and post-infrared infrared stimulated luminescence (post-IR IRSL) protocols offer opportunities for mitigating or overcoming these problems. Here we test the use of single grains of K-feldspar for luminescence dating of glacial sediments of penultimate glaciation: Guxiang glaciation, the largest known Quaternary glacier advance in SE Tibetan Plateau and was previously constrained to marine isotope stage 6 (MIS-6) by cosmogenic nuclide 10Be exposure dating [1]. We took 6 samples (GX601 to GX606) from glaciofluvial sand lens within the lateral moraines of Guxiang glaciation and 2 samples (GX607 and GX608) from overlying loess and paleosol. Dose recovery tests show that the two-step post-IR50 IRSL225 protocol was able to recover the given dose and assumed suitable for this study. The equivalent doses (Des) of each sample show large scatter, suggesting partial bleaching of these samples. It is therefore unsurprising that Des derived from the minimum age model (MAM) are smaller than those derived from the central age model (CAM). Measurement of the fading rates show that, g-values of the IR50 signal range between 3-6%, whereas those of the pIR50 IRSL225 signal are all less than 3%. After correction of the fading rates, the final ages derived from the pIR50 IRSL225 signal fall into MIS-6 if the CAM is used, and fall into MIS-5 if the MAM is used. In addition, we compared the single-grain K-feldspar and quartz ages of the younger overlying loess and paleosol samples. For both minerals, the MAM ages are smaller than the CAM ages. Moreover, the MAM ages of feldspar (~4 ka for GX607 and ~20 ka for GX608) are similar to the CAM ages of quartz, and thus larger than the MAM ages of quartz (~2 ka for GX607 and ~10 ka for GX608). This seems indicate the residual doses of feldspar are probably larger than those of quartz. For most of these samples, there is a trend that the brighter the grains, the lower their Des. The discrepancies between those results of CAM and MAM age models, quartz and feldspar, dim and bright feldspar grains, and comparation between luminescence and 10Be exposure ages, will be investigated and discussed. [ABSTRACT FROM AUTHOR]

Mitophagy is a process in which cells remove dysfunctional mitochondria and recycle their constituents in a lysosome-dependent manner. To probe this process, two different fluorescent dyes specific for mitochondria and lysosomes, respectively, are often used in combination. However, current fluorescent dyes for lysosomes cannot distinguish mitochondria-containing autolysosomes from other lysosomes. Therefore, we herein report a cyanine dye, HQO, which can simultaneously probe mitochondria and autolysosomes in live cells by exhibiting different fluorescence properties. HQO selectively accumulates in mitochondria but then transforms to the protonated HQOH+ form with the decrease of pH when dysfunctional mitochondria evolve into autolysosomes. Since HQO and HQOH+ exhibit different absorption and emission with Ex/Em at 530/650 and 710/750 nm, respectively, in a low polarity environment, such as that found in micelles, they are uniquely suited to monitor mitophagy with the ability to distinguish autolysosomes from other lysosomes. [ABSTRACT FROM AUTHOR]

DNA sequences that can form G-quadruplexes (G4s) are highly prevalent in the genome. However, the structures and functions of most G4-forming sequences in the genome are poorly understood. Therefore, the development of molecular probes for G4 recognition in biological samples, especially probes with long wavelength, are important for the basic research of G4s. Squaraines dyes exhibit sharp and intense absorption and strong emission in the red to NIR region, but very few of them have been reported as probes for the recognition of nucleic acids. Here we report the interactions of two squaraine dyes, STS and CSTS, with different kinds of DNA The dicyanomethylene-functionalized squaraine dye, CSTS, exhibits strong interaction with the parallel G4s, but no interaction with other DNA In aqueous conditions, this interaction causes the transformation of CSTS from H-aggregates to monomers, which results in decline and growth of the absorption spectra of both forms. The parallel G4s enhance the fluorescence of both STS and CSTS, but the fluorescence enhancement of CSTS is much higher than that of STS. CSTS is demonstrated to bind to G4s through end-stacking model on G-quartet surface. The high selectivity of CSTS to parallel G4s is attributed to its V-shaped rigid planar n scaffold. The high selectivity, very low background fluorescence, large absorption coefficient, and high fluorescence quantum yield make CSTS hold great promise as a long-wavelength probe for parallel G4 detection in biological samples or in vivo. [ABSTRACT FROM AUTHOR]

Putative G-quadruplex-forming sequences (PQS) are highly prevalent in human genome; however, the structures and functions of most PQSs in genome are poorly understood. Therefore, selective recognition of certain types of Gquadruplexes (G4s) is important for the study of G4s. A new light up fluorescent probe, BPBC composed of benzimidazole and carbazole moieties was designed and synthesized. BPBC possesses a crescent-shaped π-conjugated planar core that is slightly larger than the dimension of the G-quartet plane in G4s. This structure endows BPBC with excellent selectivity to parallel G4s. BPBC exhibits almost no fluorescence in the aqueous buffer condition, its fluorescence increases approximately 330-1800-fold in the presence of parallel G4s but only about 30-fold in the presence of single/double-stranded (ss/ds) DNA and 30-110-fold in the presence of antiparallel G4s. Binding studies indicate that the highly selective fluorescent response of BPBC arises from endstack binding model to G-quartet. [ABSTRACT FROM AUTHOR]

Aptamers are usually generated against a specific molecule. Their high selectivity makes them only suitable for studying specific targets. Since it is nearly impossible to generate aptamers for every molecule, it can be of great interest to select aptamers recognizing a common feature of a group of molecules in many applications. In this paper, we describe the selection of aptamers for indirect recognition of alkyl amino groups. Because amino groups are small and positive charged, we introduced a protection group, p-nitrobenzene sulfonyl (p-nosyl) to convert them into a form suitable for aptamer selection. Taking Nϵ-p-nosyl-l-lysine (PSL) as a target, we obtained a group of aptamers using the SELEX technique. Two optimized aptamers, M6b-M14 and M13a exhibit strong affinity to PSL with the Kd values in the range of 2-5 μM. They also show strong affinity to other compounds containing p-nosyl-protected amino groups except those also possessing an a-carboxyl group. Both aptamers adopt an antiparallel G-quadruplex structure when binding to targets. An aptamer beacon based on M6b-M14 showed good selectivity toward the reaction mixture of p-nosyl-Cl and alkyl amino compounds, and could recognize lysine from amino acid mixtures indirectly, suggesting that aptamers against a common moiety of a certain type of molecules can potentially lead to many new applications. Through this study, we have demonstrated the ability to select aptamers for a specific part of an organic compound, and the chemical conversion approach may prove to be valuable for aptamer selection against molecules that are generally difficult for SELEX. [ABSTRACT FROM AUTHOR]

Associations between the TAQIB and I405V polymorphisms and obesity risk were studied for a single locus as well as in combination. A total of 934 obese subjects and 924 normal controls were included in the study. TAQIB was associated with high-density lipoprotein (HDL) levels ( P < 0.001), while I405V was associated with levels of low-density lipoprotein ( P = 0.03) and total cholesterol ( P = 0.007). Less common alleles of TAQIB and I405V were associated with decreased obesity risk and further drops in odds ratio (OR) were observed in carriers with rare homozygous alleles on both loci (OR = 0.659, P = 0.02). The TAQIB B2 allele was associated with reductions in both hip circumference ( P = 0.034) and triceps skinfold thickness (TST) ( P = 0.045), although this effect was completely abolished after controlling for HDL levels. The 405V variant was associated with reductions in hip circumference ( P = 0.031), body fat composition ( P = 0.039) and TST ( P = 0.036); these effects were weakened ( P < 0.1) after controlling for HDL levels. In conclusion, less common alleles of TAQIB and I405V appear to be modestly associated with obesity risk in an adult Chinese population. Adjustments for HDL levels completely (TAQIB) or partially (I405V) abolished the observed association. [ABSTRACT FROM AUTHOR]

Background: Beclin 1, an important autophagy-related protein in human cells, is involved in cell death and cell survival. Beclin 1 mapped to human chromosome 17q21. It is widely expressed in normal mammary epithelial cells. Although down-regulated expression with mono-allelic deletions of beclin 1 gene was frequently observed in breast tumors, whether there was other regulatory mechanism of beclin 1 was to be investigated. We studied the expression of beclin 1 and explored the possible regulatory mechanisms on its expression in breast tumors. Methods: 20 pairs of tumors and adjacent normal tissues from patients with sporadic breast invasive ductal cancer (IDCs) were collected. The mRNA expression of beclin 1 was detected by real-time quantitative RT-PCR. Loss of heterozygosity (LOH) was determined by real-time quantitative PCR and microsatellite methods. The protein expression of beclin 1, p53, BRCA1 and BRCA2 was assessed by immunohistochemistry. CpG islands in 5' genomic region of beclin 1 gene were identified using MethylPrimer Program. Sodium bisulfite sequencing was used in examining the methylation status of each CpG island. Results: Decreased beclin 1 mRNA expression was detected in 70% of the breast tumors, and the protein levels were co-related to the mRNA levels. Expression of beclin 1 mRNA was demonstrated to be much higher in the BRCA1 positive tumors than that in the BRCA1 negative ones. Loss of heterozygosity was detected in more than 45% of the breast tumors, and a dense cluster of CpG islands was found from the 5' end to the intron 2 of the beclin 1 gene. Methylation analysis showed that the promoter and the intron 2 of beclin 1 were aberrantly methylated in the tumors with decreased expression. Conclusions: These data indicated that LOH and aberrant DNA methylation might be the possible reasons of the decreased expression of beclin 1 in the breast tumors. The findings here shed some new light on the regulatory mechanisms of beclin 1 in breast cancer. [ABSTRACT FROM AUTHOR]

Background: The establishment of new methods to detect human genetic variations, such as single nucleotide polymorphisms, is of importance in hereditary disease diagnosis and pharmacogenomics. Several single nucleotide polymorphism genotyping technologies have been presented in recent years. However, techniques which would allow accurate, fast and cheap allelic determination and multiple single nucleotide polymorphism detection in parallel are still in great need. Methods: Here, we present a new genotyping technique based on gap ligase chain reaction and a fluorescent polystyrene microsphere measurement platform. We chose the human polymorphism rs3730386 as our candidate to establish this method. Probes for gap ligase chain reaction were designed to recognize the target alleles sensitively and specifically and to produce templates for amplifying the correspondent target fragments used in the following hybridization. The genotypes were finally determined by a hybridization process based on the Luminex fluorescent polystyrene microspheres measurement platform. Results: This method was successfully applied for the detection of selected single nucleotide polymorphisms with high sensitivity and specificity. The genotypes were validated by DNA sequencing. Conclusions: The new genotyping method benefited from the high sensitivity and specificity of gap ligase chain reaction and the detection platform of Luminex. The method allows multiplex analysis of single nucleotide polymorphism, because 100 types of microspheres are available from Luminex. Clin Chem Lab Med 2008;46:486–9. [ABSTRACT FROM AUTHOR]

In recent years, it has been shown that yeast, a unicellular organism, undergoes apoptosis in response to various factors. Here we demonstrate that the highly effective anticancer agent arsenic induces apoptotic process in yeast cells. Reactive oxygen species (ROS) production was observed in the process. Moreover, mitochondrial membrane potential decreased after arsenic treatment. Resistance of the rho0 mutant strain (lacking mtDNA) to arsenic provides further evidence that this death process involves mitochondria. In addition, hypersensitivity of Δ sod1 to arsenic suggests the critical role of ROS. Cell death and DNA fragmentation decreased in a Δ yca1 deletion mutant, indicating the participation of yeast caspase-1 protein in apoptosis. The implications of these findings for arsenic-induced apoptosis are discussed. [ABSTRACT FROM AUTHOR]

Background: The study of microRNAs (miRNAs) is attracting great considerations. Recent studies revealed that miRNAs play as important regulators of gene expression and some even as cancer players or inhibitors. Many studies try to discover new miRNAs and reveal the miRNA expression profile in cancer using a SAGE-based total RNA clone method. However, the data processing of this method is labor-intensive with several different biological databases and more than ten data processing steps involved. Results: With miRAS, miRNAs and possible miRNA candidates contained in the submitted sequencing data were obtained together with their expression profile. The functions of known and predicted miRNAs were then analyzed by miRNA target prediction followed by target gene annotations. Finally, to extract the biological significance of the miRNAs in the samples, further annotations of the known miRNA and target genes were performed by collecting the public expression datasets of miRNA and target genes in normal and cancer tissues. Conclusion: We introduce a web-based analysis platform called miRNA Analysis System (miRAS), for processing and analyzing of the sequence data obtained from the total RNA clone method. The system was built on generalizing the study of a liver cancer cell line total RNA sequencing project. miRAS is freely available on the web. [ABSTRACT FROM AUTHOR]

The spike (S) protein, a main surface antigen of the SARS coronavirus (SARS-CoV), is considered to be one of the most important protective antigen candidates for targets for vaccine design against the virus. In this study, a secreted recombinant expression plasmid, pVAX-S1, encoding the partial S protein with a signal peptide, was constructed and used to immunize BALB/c mice through electroporation. It was demonstrated that the eukaryotic expression vector pVAX-S1 was successfully constructed by restriction enzyme and sequence analysis. The expressed protein could be detected specifically by Western blot analysis. The serum IgG level of the vaccine group mice was significantly higher than that of the corresponding control group at day 14 after vaccination ( P < 0.05). The vaccine group demonstrated significantly higher S1 protein lymphocyte proliferation index (LPI) than the control groups ( P < 0.05). Furthermore, in the experimental group, a decrease in the ratio of CD4+ to CD8+ T-lymphocytes and an increase level of IFN-gamma in serum were observed. However, interleukin-4 (IL-4) was not detectable in two groups. These results strongly demonstrated that the pVAX-S1 plasmid could induce humoral and cellular immune responses in mice, and may be a potential candidate for a DNA vaccine against the SARS coronavirus. [ABSTRACT FROM AUTHOR]