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Hydraulic fracturing is considered the main stimulation method to develop shale gas reservoirs. Due to its strong heterogeneity, the shale gas formation is typically embedded with geological discontinuities such as bedding planes and natural fractures. Many researchers realized that the interaction between natural fractures and hydraulic fractures plays a crucial role in generating a complex fracture network. In this paper, true tri-axial hydraulic fracturing tests were performed on polymethyl methacrylate (PMMA), on which pre-existing fracture was pre-manufactured to simulate natural fracture. A cohesive model has been developed to verify the results of the experimental tests. The key findings demonstrate that the experimental results agreed well with the numerical simulation outcomes where three main interaction modes were observed: crossing; being arrested by opening the pre-existing fracture; being arrested without dilating the pre-existing fracture. Crossing behavior is more likely to occur with the approaching angle, horizontal stress difference, and injection rate increase. Furthermore, the higher flow rate might assist in reactivating the natural fractures where both sides of the pre-existing fractures were reactivated as the injection rate increased from 5 to 20 mL/min. Additionally, hydraulic fractures show a tendency to extend vertically rather than along the direction of maximum horizontal stress when they are first terminated at the interface. This research may contribute to the field application of hydraulic fracturing in shale gas formation. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to evaluate the safety and feasibility of simultaneous surgery for patients with primary esophageal and lung cancers. Methods Patients with primary esophageal and lung cancers who underwent simultaneous surgical procedures between January 2016 and January 2022 were retrospectively analyzed. The data of patients who underwent esophagectomy and lobectomy (group EL) were compared with those of patients who underwent esophagectomy and sublobar resection (group ES). Results A total of 21 patients were included with an average age of 64.62 ± 5.24 years. Group EL contained 8 patients and group ES contained 13 patients. All procedures were completed uneventfully with a mean operative time of 251.19 ± 66.93 minutes. Pulmonary complications occurred in six (28.57%) patients. Other complications included anastomotic leakage in 1 patient, pleural effusion requiring drainage in 8 patients, atrial fibrillation in 2 patients, and incision infection in 1 patient. All patients were followed up for 30.23 ± 21.82 months. During the follow-up period, nine patients had a recurrence of cancer and died of tumor progression, and one patient died of a tracheothoracogastric fistula. Complications and mortality in group EL did not increase when compared to those in group ES. Conclusion It is safe and feasible to perform a single-stage surgical procedure for patients with primary esophageal and lung cancers. Simultaneous esophagectomy and lobectomy did not increase postoperative complications or mortality compared with esophagectomy and sublobar resection. [ABSTRACT FROM AUTHOR]

In China, the preservation of refrigerated daggertooth piker congers (Muraenesox cinereus) has received increasing attention in recent years due to the increased demand for fresh congers. In this study, the effect of tea polyphenols (0.1%, 0.2%, 0.4%) and chitosan (0.5%, 1%, 2%) on daggertooth piker conger preservation was evaluated based on major spoilage bacteria detected during cold storage. The preservation quality was assessed through sensory scores, TVB-N, and TBARS concentrations and plate counts of total bacteria, H2S-producing bacteria, and Pseudomonas. The results showed that all concentrations of tea polyphenols and chitosan successfully inhibited spoilage bacterial growth, suppressed TVB-N (total volatile basic nitrogen) and TBARS (thiobarbituric acid-reactive substances) generation, and improved the sensory score, although the results were not dose-dependent. The optimal concentrations of tea polyphenols and chitosan were 0.2% and 0.5%, respectively. A later assessment of the synergistic effect of tea polyphenols and chitosan coating conger samples with both preservatives at their optimal concentration. Possibly, due to their mechanic difference in bacteriostasis, the combined treatment significantly inhibited the growth of H2S-producing bacteria and Pseudomonas, indicating a better antibacterial effect than when using one of the preservatives alone. Finally, combined tea polyphenol and chitosan treatment prolonged the first- and second-grade freshness of refrigerated congers for 4-6 days. [ABSTRACT FROM AUTHOR]

Introduction: Shot put throwing techniques are divided into spinning and sliding, and must have certain physical qualities such as speed, explosive power, and coordination. The purpose of this study was to analyze the effect of neuromuscular electrical stimulation intervention training on shot put throwing performance and to explore the shot put throwing technique and kinematic differences at each movement stage. Methods: Fifteen male college students who had not received electrical stimulation previously were the research participants. Two high-speed cameras were used to obtain synchronous images of shot put throwing actions of the participants before and after electrotherapy. Three-dimensional kinematic image analysis was performed using the Kwon 3D motion analysis system. The Wilcoxon signed-rank test was used to test differences in shot put parameters at each action stage before and after electrotherapy. Results: Throwing distance was longer (p < .01) and throwing speed was faster (p < .01) after electrotherapy than before electrotherapy. The ankle joint angle with the lowest center of gravity (p < .05), ankle joint angle of the left foot off the ground (p < .01), and ankle joint angle of the right foot was off the ground (p < .05) were greater after electrotherapy than before electrotherapy. The shoulder-hip separation angle in the throwing stage was smaller (p < .05), shoulder-hip separation angle in the turning stage was larger (p < .05), and left ankle joint angle in the turning stage was smaller (p < .05) after electrotherapy than before electrotherapy. Conclusion: Neuromuscular electrical stimulation has an impact on shot put throwing. Appropriate electrical stimulation can enhance muscle activation, increase muscle contraction force, and improve athletic ability and shot put throwing performance. [ABSTRACT FROM AUTHOR]

Prolyl hydroxylase-1 (PHD1), a member of the hypoxia inducible factor (HIF)-PHD family, plays an important role in regulating the stability of HIFs. The nuclear factor-κB (NF-κB) pathway consists of a family of transcription factors that play critical roles in inflammation, immunity, cell proliferation, differentiation, and survival. In this study, we demonstrate that PHD1 can inhibit NF-κB activity and its target genes in lung cancer cells based on both over-expression and RNA interference-mediated knockdown of PHD1 in human A549 lung cancer cells and HEK293 T cells. Of medical importance, PHD1 could induce cell cycle arrest in lung cancer cells, resulting in the suppression of cell proliferation. Xenograft tumor growth assays indicate that PHD1 plays a critical role in suppressing lung cancer growth. These findings reveal a new role of PHD1 in lung cancer and provide new treatment perspectives for cancer therapy by characterizing PHD1 as a potential target. [ABSTRACT FROM AUTHOR]

This paper presents an optimal design for a new humidity sensor composed of a dual-resonator oscillator configuration with an operation frequency of 300 MHz, and a polyaniline (PANI) coating deposited along the resonation cavity of the sensing device. To improve the corrosion resistance of the sensor chip, Al/Au electrodes were used to form the SAW resonator. Prior to device fabrication, the coupling of modes (COM) model was used for the performance prediction and optimal design parameters determination. Two SAW resonators with Al/Au electrodes were fabricated on an ST-X quartz substrate, and used as the frequency control element in the feedback path of an oscillator circuit. A PANI thin coating was deposited onto the resonator cavity of the sensing device by a spinning approach as the sensor material for relative humidity (RH) detection. High detection sensitivity, quick response, good repeatability and stability were observed from the sensor experiments at room temperature. [ABSTRACT FROM AUTHOR]

Graphene-based three-dimensional porous macrostructures are believed of great importance in various applications, e.g. supercapacitors, photovoltaic cells, sensors and high-efficiency sorbents. However, to precisely control the microstructures and properties of this material to meet different application requirements in industrial practice remains challenging. We herein propose a facile and highly effective strategy for large-range tailoring the porous architecture and its properties by a modified freeze casting process. The pore sizes and wall thicknesses of the porous graphene can be gradually tuned by 80 times (from 10 to 800 mm) and 4000 times (from 20 nm to 80 mm), respectively. The property experiences the changing from hydrophilic to hydrophobic, with the Young's Modulus varying by 15 times. The fundamental principle of the porous microstructure evolution is discussed in detail. Our results demonstrate a very convenient and general protocol to finely tailor the structure and further benefit the various applications of porous graphene. [ABSTRACT FROM AUTHOR]

Two-dimensional nanosheets have attracted tremendous attention because of their promising practical application and theoretical values. The atomic-thick nanosheets are able to not only enhance the intrinsic properties of their bulk counterparts but also give birth to new promising properties. Herein, we highlight an available pathway to prepare the ultrathin graphitic-phase C3N4 (g-C3N4) nanosheets by a "green" liquid exfoliation route from bulk g-C3N4 in water for the first time. The as-obtained ultrathin g-C3N4 nanosheet solution is very stable in both the acidic and alkaline environment and shows pH-dependent photoluminenscence (PL). Compared to the bulk g-C3N4, ultrathin g-C3N4 nanosheets show enhanced intrinsic photosbsorption and photoresponse, which induce their extremely high PL quantum yield up to 19.6%. Thus, benefiting from the inherent blue light PL with high quantum yields and high stability, good biocompatibility, and nontoxicity, the water-soluble ultra-thin g-C3N4 nanosheet is a brand-new but promising candidate for bioimaging application. [ABSTRACT FROM AUTHOR]

A more effective experimental method is used to analyze the effect of magnetic damping on a nonferromagnetic air track. Due to the continuous interaction between the horizontal air track and the moving magnets fixed on the air-track glider, the experiment can be easily done with low-cost photoelectric detecting techniques. A simple model is proposed based on Faraday's law, the Lorentz force law, and Ampere's law. Analytic expressions for the position, the velocity, and the magnetic damping force of the moving magnets as a function of time are obtained. Systematic measurements were performed and the results are in good agreement with the model. The method provides a simple teaching platform for introductory physics demonstrations and undergraduate courses in experimental physics. [ABSTRACT FROM AUTHOR]

Temporal coding precision of bushy cells in the ventral cochlear nucleus (VCN), critical for sound localization and communication, depends on the generation of rapid and temporally precise action potentials (APs). Voltage-gated potassium (Kv) channels are critically involved in this. The bushy cells in rat VCN express Kv1.1, 1.2, 1.3, 1.6, 3.1, 4.2, and 4.3 subunits. The Kv1.1 subunit contributes to the generation of a temporally precise single AP. However, the understanding of the functions of other Kv subunits expressed in the bushy cells is limited. Here, we investigated the functional diversity of Kv subunits concerning their contributions to temporal coding. We characterized the electrophysiological properties of the Kv channels with different subunits using whole cell patch-clamp recording and pharmacological methods. The neuronal firing pattern changed from single to multiple APs only when the Kv1.1 subunit was blocked. The Kv subunits, including the Kv1.1, 1.2, 1.6, or 3.1, were involved in enhancing temporal coding by lowering membrane excitability, shortening AP latencies, reducing jitter, and regulating AP kinetics. Meanwhile, all the Kv subunits contributed to rapid repolarization and sharpening peaks by narrowing half-width and accelerating fall rate, and the Kv1.1 subunit also affected the depolarization of AP. The Kv1.1, 1.2, and 1.6 subunits endowed bushy cells with a rapid time constant and a low input resistance of membrane for enhancing spike timing precision. The present results indicate that the Kv channels differentially affect intrinsic membrane properties to optimize the generation of rapid and reliable APs for temporal coding. NEW & NOTEWORTHY This study investigates the roles of Kv channels in effecting precision using electrophysiological and pharmacological methods in bushy cells. Different Kv channels have varying electrophysiological characteristics, which contribute to the interplay between changes in the membrane properties and regulation of neuronal excitability which then improve temporal coding. We conclude that the Kv channels are specialized to promote the precise and rapid coding of acoustic input by optimizing the generation of reliable APs. [ABSTRACT FROM AUTHOR]

Vacuum filtration enables the fabrication of large-area graphene-based membranes (GBMs), possessing a smoother surface than that by spray, spin coating or drop casting. However, due to the strong interaction with substrates, the separation of thin GBMs from the filter is problematic. Conventional stamping separation/transfer of graphene oxide (GO) thin films requires another substrate and pressing for >10 h, which may damage the delicate structure of the transfer substrates. Other methods require GO to be reduced on filters before separation, thus limiting the reduction methods. Inspired by a coagulation bath that enables rapid formation of ultrastrong GO fibers, we present an ultrafast (<1 min) and solution-assisted strategy to fabricate smooth and freestanding GO films. The diverse interfacial energy of hydrogen bonds also demonstrates another reason for the successful separation. The film thickness ranges from 45 nm to several micrometers. When used as a composite of counter electrodes in dye sensitized solar cells, it showed higher (8.58%) power conversion efficiency than its spin-(7.71%) and spray-coated (8.07%) counterparts. It also showed promising performance in capacitive humidity sensors. The capacitance varied by three orders of magnitude in the range of the relative humidity of 15%–95%. Therefore the strategy realizes an ultrafast and high-quality film production which is suitable for various applications. [ABSTRACT FROM AUTHOR]

To accomplish their functions, proteins have to achieve different conformations accompanied by conformational transitions. However, the relationship between the preference of amino acids and the stability of the secondary structure is still unclear. Here we perform molecular simulations on a series of helical structures. Our data show that the dissociation energy of the helical structure is related to the preference of amino acids, and the electrostatic repulsion of the residue i and i + 3/4 with the same sign of charge destabilizes the alpha helix. [ABSTRACT FROM AUTHOR]

We propose a new application of the optical adiabatic passage effect for the excitation of a thermal atomic beam, which will be used in the calcium active optical clock to produce population inversion. A comparison between the optical adiabatic passage effect and the Rabi p pulse is investigated, 99% of the calcium atoms in the atomic beam that has a wide velocity distribution will be excited to the upper state for population inversion using the adiabatic passage, while 76% at most will be excited to the excited state using the p pulse with suitable parameters. [ABSTRACT FROM AUTHOR]

Previous studies have concluded that the increase in vegetation in the arid northwest of China is related to precipitation rather than temperature. However, these studies neglected the effects of climate warming on water availability that arise through changes in the melting characteristics of this snowy and glaciated region. Here, we characterized vegetation changes using the newly improved third-generation Global Inventory Modeling and Mapping Studies Normalized Difference Vegetation Index (GIMMS-3g NDVI) from 1982 to 2011. We analyzed the temperature and precipitation trends based on data from 51 meteorological stations across Northwest China and investigated changes in the glaciers using Gravity Recovery and Climate Experiment (GRACE) data. Our results indicated an increasing trend in vegetation greenness in Northwest China, and this increasing trend was mostly associated with increasing winter precipitation and summer temperature. We found that the mean annual temperature increased at a rate of 0.04 °C per year over the past 30 years, which induced rapid glacial melting. The total water storage measured by GRACE decreased by up to 8 mm yr-1 and primarily corresponded to the disappearance of glaciers. Considering the absence of any observed increase in precipitation in the growing season, the vegetation growth may have benefited from the melting of glaciers in high-elevation mountains (i.e., the Tianshan Mountains). Multiple regression analysis showed that temperature was positively correlated with NDVI and that gravity was negatively correlated with NDVI; together, these variables explained 84% of the NDVI variation. Our findings suggest that both winter precipitation and warming-induced glacial melting increased water availability to the arid vegetation in this region, resulting in enhanced greenness. [ABSTRACT FROM AUTHOR]

Buckle propagation is an essential concern in offshore pipeline design. Once the propagation occurs, it may cause unavoidable failure of an entire pipeline. With the consideration of both longitudinal and hoop deformation behavior of pipeline, a ring-truss theory was analytically established in this study. Laboratory experiments were conducted in full-scale hyperbaric chamber in order to verify the analytical equation. It was observed that the length of transition zone has great influence on determination of propagation pressure. Due to the difficulties of measurement during test process, the length of transition zone was obtained using the finite element simulation. The comparison of propagation pressure between the current study and published model shows that for small diameter to thickness ratio, the ring-truss model is the one that is closest to the actual situation. [ABSTRACT FROM AUTHOR]

Cryptocaryon irritans are the main pathogens of white spot disease in marine teleost. However, the occurrence of cryptocaryoniasis is influenced by several abiotic factors including the pH. To explore the effect of pH on the life cycle of C. irritans (encystment, cleavage, and hatchability), protomonts and tomonts of C. irritans were incubated in seawater of 10 different pH levels (2-11). pH 8 was used as the control. The change in morphology and infectivity of theronts that hatched from tomonts against Larimichthys crocea were then recorded. We found that pH 6-9 had no significant effect on the encystment, cleavage, and hatching of the parasites. However, pH beyond this limit decreased the cleavage and hatching of the tomonts. Furthermore, extreme pH decreased the number of theronts hatched by each tomont and the pathogenicity of the theronts, but increased the aspect ratio of the theronts. Infectivity experiments further revealed that extreme pH significantly decreased the infectivity of C. irritans against L. crocea. In conclusion, the C. irritans can survive in pH of 5 to 10, but pH 6-9 is the optimal range for the reproduction and infectivity of C. irritans. However, extreme pH negatively affects these aspects. [ABSTRACT FROM AUTHOR]

Nowadays, dealing with the complex oil/water contamination that contains both oil/water mixtures and emulsions with desirable performance remains a huge challenge. Complicated fabrication procedures, low flux, and efficiency are shortcomings of the known materials. Herein, a facile and effective laser-assisted strategy is proposed to prepare super-hydrophobic graphene/PDMS paper (L-G-P), which perfectly takes advantage of both naturally strong capillary of paper tissue and high-quality graphene. Specifically, graphene is obtained by reducing graphene oxide via laser irradiation, which avoids introducing chemical reducing agents that are either hazardous or hard to separate. Meanwhile, the super-intensive instantaneous energy would create abundant defects on graphene sheets, thus the specific surface area increased by 25%. As for oil/water mixtures, the efficient sorption/separation can realize over 99.99% deep clean, meanwhile showing excellent durability after repeated cycles. As for water-in-oil emulsions, the high separation flux of surfactant-stabilized emulsions could reach 4421 L m-2 h-1 with an efficiency up to 99.85%. Moreover, the mechanical property of the composite was 80.50% stronger than uncoated paper tissue. The proposed L-G-P with durable and efficient oil/water separation performance is a promising material for practical applications for treating oil-contaminated wastewater in harsh environments. [ABSTRACT FROM AUTHOR]

Humidity sensors have been extensively used in various fields, and numerous problems are encountered when using humidity sensors, including low sensitivity, long response and recovery times, and narrow humidity detection ranges. Using graphene oxide (G-O) films as humidity sensing materials, we fabricate here a microscale capacitive humidity sensor. Compared with conventional capacitive humidity sensors, the G-O based humidity sensor has a sensitivity of up to 37800% which is more than 10 times higher than that of the best one among conventional sensors at 15%-95% relative humidity. Moreover, our humidity sensor shows a fast response time (less than 1/4 of that of the conventional one) and recovery time (less than 1/2 of that of the conventional one). Therefore, G-O appears to be an ideal material for constructing humidity sensors with ultrahigh sensitivity for widespread applications. [ABSTRACT FROM AUTHOR]

A new micro gyroscope based on the surface acoustic wave (SAW) gyroscopic effect was developed. The SAW gyroscopic effect is investigated by applying the surface effective permittivity method in the regime of small ratios of the rotation velocity and the frequency of the SAW. The theoretical analysis indicates that the larger velocity shift was observed from the rotated X-112°Y LiTaO3 substrate. Then, two SAW delay lines with reverse direction and an operation frequency of 160 MHz are fabricated on a same X-112°Y LiTaO3 chip as the feedback of two SAW oscillators, which act as the sensor element. The single-phase unidirectional transducer (SPUDT) and combed transducers were used to structure the delay lines to improve the frequency stability of the oscillator. The rotation of a piezoelectric medium gives rise to a shift of the propagation velocity of SAW due to the Coriolis force, resulting in the frequency shift of the SAW device, and hence, the evaluation of the sensor performance. Meanwhile, the differential structure was performed to double the sensitivity and compensate for the temperature effects. Using a precise rate table, the performance of the fabricated SAW gyroscope was evaluated experimentally. A sensitivity of 1.332 Hz deg-1 s at angular rates of up to 1,000 deg s-1 and good linearity are observed. [ABSTRACT FROM AUTHOR]

The influence of poly(vinyl alcohol) (PVA) in the synthesis of SBA-15 was investigated. It was found that, by the addition of PVA, the surface area and porosity of SBA-15 is increased, while the structure and size of the mesopores remain unchanged. Nitrogen sorption measurements indicate that PVA introduces additional pores with pore sizes of around 2 nm into the pore wall. Thus, a simple way of improving the porosity of mesoporous silica is presented that could enhance transport of substrates through the porous system, important for catalytic applications and also beneficial for replication and nanocasting purposes. We, furthermore, show that a heterogeneous catalyst, Pt/SBA-15, with high surface area can be prepared by the addition of PVA-stabilized platinum nanoparticle sols. [ABSTRACT FROM AUTHOR]

In order to discover novel derivatives in the anti-tumor field, reported anti-tumor pharmacophores (uridine, uracil, and thymine) were combined with 2-methoxyestradiol, which has been characterized as having excellent biological properties in terms of anti-tumor activity. Thus, 20 hybrids were synthesized through etherification at the 17β-OH or 3-phenolic hydroxyl group of 2-methoxyestradiol, and evaluated for their biological activities against the human breast adenocarcinoma MCF-7 cell lines, human breast cancer MDA-MB-231 cell lines, and the normal human liver L-O2 cell lines. As a result, all the uridine derivatives and single-access derivatives of uracil/thymine possessed good anti-proliferative activity against tested tumor cells (half maximal inhibitory concentration values from 3.89 to 19.32 µM), while only one dual-access derivative (21b) of thymine possessed good anti-proliferative activity (half maximal inhibitory concentration ≈ 25 µM). Among them, the uridine derivative 11 and the single-access derivative of uracil 12a possessed good anti-proliferative selectivity against tested tumor cells. Furthermore, basic mechanism studies revealed that hybrids 11 and 12a could induce apoptosis in MCF-7 cells through mitochondrial pathway. These hybrids induced morphological changes in MCF-7 cells, causing mitochondrial depolarization. These two hybrids also had the following effects: arrest of the cell cycle at the G2 phase; up regulation of Apaf-1, Bax, and cytochrome c; down regulation of Bcl-2 and Bcl-xL for both mRNA and protein; and increase of the expression for caspase-8 and -9. Finally, apoptotic effector caspase-3 was increased, which eventually caused nuclear apoptosis at least through an intrinsic pathway in the mitochondria. Additionally, hybrids 11 and 12a could specifically bind to estradiol receptor alpha in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

Background: The prognosis of spinal cord injury (SCI) is closely related to secondary injury, which is dominated by neuroinflammation. There is evidence that α-synuclein aggregates after SCI and that inhibition of α-synuclein aggregation can improve the survival of neurons after SCI, but the mechanism is still unclear. This study was designed to investigate the effects of α-synuclein on neuroinflammation after SCI and to determine the underlying mechanisms.Method: A T3 spinal cord contusion model was established in adult male Sprague-Dawley rats. An SNCA-shRNA-carrying lentivirus (LV-SNCA-shRNA) was injected into the injury site to block the expression of α-synuclein (forming the SCI+KD group), and the SCI and sham groups were injected with an empty vector. Basso-Beattie-Bresnahan (BBB) behavioural scores and footprint analysis were used to detect motor function. Inflammatory infiltration and myelin loss were measured in the spinal cord tissues of each group by haematoxylin-eosin (HE) and Luxol Fast Blue (LFB) staining, respectively. Immunohistochemistry, Western blot analysis, and RT-qPCR were used to analyse protein expression and transcription levels in the tissues. Immunofluorescence was used to determine the morphology and function of glial cells and the expression of matrix metalloproteinase-9 in the central canal of the spinal cord. Finally, peripheral serum cytokine levels were determined by enzyme-linked immunosorbent assay.Results: Compared with the SCI group, the SCI+KD group exhibited reduced inflammatory infiltration, preserved myelin, and functional recovery. Specifically, the early arrest of α-synuclein inhibited the pro-inflammatory factors IL-1β, TNF-α, and IL-2 and increased the expression of the anti-inflammatory factors IL-10, TGF-β, and IL-4. The neuroinflammatory response was regulated by reduced proliferation of Iba1+ microglia/macrophages and promotion of the shift of M1-polarized Iba1+/iNOS+ microglia/macrophages to M2-polarized Iba1+/Arg1+ microglia/macrophages after injury. In addition, compared with the SCI group, the SCI+KD group also exhibited a smaller microglia/astrocyte (Iba1/GFAP) immunostaining area in the central canal, lower MMP-9 expression, and improved cerebrospinal barrier function.Conclusion: Lentivirus-mediated downregulation of α-synuclein reduces neuroinflammation, improves blood-cerebrospinal barrier function, promotes functional recovery, reduces microglial activation, and promotes the polarization of M1 microglia/macrophages to an M2 phenotype to confer a neuroprotective immune microenvironment in rats with SCI. [ABSTRACT FROM AUTHOR]

Targeted drugs have been widely used in the treatment of patients with lung cancer, particularly for those with non-small cell lung cancer (NSCLC). Plasma cell-free DNA is an emerging clinical tool for the detection of epidermal growth factor receptor (EGFR) gene mutation in patients with lung cancer. Detection of circulating tumor (ct) DNA by droplet digital PCR (ddPCR) is a highly sensitive and minimally invasive alternative for the assessment and management of cancer. In the present study, four ddPCR systems were developed to detect the 19DELs, L858R, T790M and C797S mutations of the EGFR gene in plasma ctDNA samples, and all exhibited higher sensitivity compared with the amplification refractory mutation system (ARMS)-PCR assays. The results revealed that the sensitivity of the ddPCR assays for the four major types of EGFR mutant reached 0.04%. In total, 50 plasma ctDNA samples were collected from patients with NSCLC to detect the 19DELs, L858R, T790M and C797S mutations by ddPCR and ARMS-PCR. All the mutations except for C797S were detected and the concordance rates between ddPCR and ARMS-PCR were 96% (19DELs), 98% (L858R) and 100% (T790M). The fraction of EGFR mutation ranged from 0.43 to 68.07% using the ddPCR method. Therefore, the present study suggests that the four ddPCR testing systems could be used for early detection of EGFR mutations in plasma samples, so that patients can better select the targeted drugs according to the EGFR mutation. [ABSTRACT FROM AUTHOR]

MicroRNA-219 (miR-219) regulates the proliferation and differentiation of oligodendrocyte precursor cells (OPCs) during central nervous system (CNS) development. OPCs only differentiate into oligodendrocytes (OLs) in the healthy CNS, but can generate astrocytes (As) after injury. We hypothesized that miR-219 may modulate OPC proliferation and differentiation in a cervical C5 contusion spinal cord injury (SCI) model. After injury, we observed a decrease in the miR-219 level and quantity of OLs and an increase in the number of OPCs and As. Silencing of miR-219 by its antagomir in vivo produced similar results, but of greater magnitude. Overexpression of miR-219 by its agomir in vivo increased the number of OLs and suppressed generation of OPCs and As. Luxol fast blue staining confirmed that SCI caused demyelination and that the extent of demyelination was attenuated by miR-219 overexpression, but aggravated by miR-219 reduction. Monocarboxylate transporter 1 (MCT-1) may be implicated in the regulation of OPC proliferation and differentiation mediated by miR-219 following contusion SCI. Collectively, our data suggest that miR-219 may mediate SCI-induced OPC proliferation and differentiation, and MCT-1 may participate in this process as a target of miR-219. [ABSTRACT FROM AUTHOR]

Oxidative stress and inflammation are two key secondary pathological mechanisms following spinal cord injury (SCI). Ketogenic diet (KD) and its metabolite β-hydroxybutyrate have been found to exhibit anti-oxidative and anti-inflammatory properties both in rats with SCI and in healthy rats; however, the underlying mechanisms are not yet fully understood. We investigated the effects of KD on the suppression of oxidative stress and inflammation, activation of nuclear factor-E2 related factor 2 (Nrf2), and inhibition of the nuclear factor-κB (NF-κB) signaling pathway in rats with SCI. We assessed functional recovery and evaluated the status of oxidative stress and inflammation using tests of superoxide dismutase and myeloperoxidase activity. We further assessed the presence of the proinflammatory cytokines tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and interferon γ (IFN-γ) by ELISA. Western blotting was used to detect Nrf2 and NF-κB pathway-associated proteins in spinal cord tissue. Finally, we measured the levels of the NF-κB downstream genes TNF-α, IL-1β, and IFN-γ by western blotting and real-time quantitative PCR. Following SCI, KD improved functional recovery, attenuated oxidative stress and inflammation, and induced Nrf2 activation. In addition, KD suppressed the NF-κB pathway and the expression of TNF-α, IL-1β, and IFN-γ. Together, these findings provide new insight into the underlying regulatory mechanisms of KD. [ABSTRACT FROM AUTHOR]

Self-assembly and molecular imprinting technologies are very attractive technologies for the development of artificial recognition systems and provide chemical recognition based on need and not happenstance. In this paper, we employed a β-cyclodextrin derivative surface acoustic wave (SAW) chemical sensor for detecting the chemical warfare agents (CWAs) sarin (O-Isoprophyl methylphosphonofluoridate, GB). Using sarin acid (isoprophyl hydrogen methylphosphonate) as an imprinting template, mono[6-deoxy-6-[(mercaptodecamethylene)thio]]-β-cyclodextrin was prepared by self-assembled method on one of the SAW oscillators. After templates' removal, a sensitive and selective molecular imprinting (MIP) monolayer for GB was prepared. Electrochemical impedance spectroscopy and atomic force microscope (AFM) were used to characterize this film. Comparing the detection results to GB by MIP film and non-MIP film, the molecularly imprinting effect was also proved. The resulting SAW sensor could detect sarin as low as 0.10 mg/m³ at room temperature and the frequency shift was about 300 Hz. The response frequency increased linearly with increasing sarin concentration in the range of 0.7 mg/m³~3.0 mg/m³. When sarin was detected under different temperatures, the SAW sensor exhibited outstanding sensitivity and reliability. [ABSTRACT FROM AUTHOR]

Background The choice between volar locking plates (VLP) and external fixation (EF) for unstable distal radius fractures have not reached a consensus. The meta-analysis of randomized controlled trials was performed to compare VLP with EF to determine the dominant strategy. Materials and methods Meta-analysis was performed with a systematic search of studies conducted by using the PubMed, Embase, and Cochrane Central Register of Controlled Trials databases. The randomized controlled trials that compared VLP with EF was identified. Characteristics, functional outcomes, radiological results, and complications were manually extracted from all the selected studies. Results Six studies encompassing 445 patients met the inclusion criteria. There was significant difference between two procedures in disabilities of the arm shoulder and hand scores at 3,6, and 12 mo, visual analogue scale at 6 mo, grip strength at 3 mo, supination at 3 and 6 mo, extension at 3 mo, ulnar variance at 12 mo, and reoperation rate at 12 mo, postoperatively. However, there was no significant difference between flexion, pronation, radial deviation, and ulnar deviation at all follow-up points postoperatively and overall complications at 12 mo, postoperatively. Conclusions EF had less reoperative rate due to complications, however, VLP had advantages in functional recovery in the early period after surgery, but two methods had similar functional recovery at 12 mo, postoperatively. Clinician should make the treatment decision with great caution for the patients who sustained unstable distal radial fractures. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests that ubiquitin-specific protease 22 (USP22) has great clinicopathologic significance in oncology. In this study, we investigated the role of USP22 in human NSCLC tumorigenesis along with the underlying mechanisms of action. First, we determined the expression of USP22 in human NSCLC, as well as normal tissues and cell lines. We then studied the effects of USP22 silencing by shRNA on NSCLC cell growth in vitro and tumorigenesis in vivo, along with the effect on the p53 pathway. We found that USP22 is overexpressed in human NSCLC tissues and cell lines. USP22 silencing by shRNA inhibits proliferation, induces apoptosis and arrests cells at the G0/G1 phases in NSCLC cells and curbs human NSCLC tumor growth in a mouse xenograft model. Additionally, USP22 silencing downregulates MDMX protein expression and activates the p53 pathway. Our co-immunoprecipitation analysis shows that USP22 interacts with MDMX in NSCLC cells. Furthermore, MDMX silencing leads to growth arrest and apoptosis in NSCLC cells, and over-expression of MDMX reverses the USP22 silencing-induced effects. Taken together, our results suggest that USP22 promotes NSCLC tumorigenesis in vitro and in vivo through MDMX upregulation and subsequent p53 inhibition. USP22 may represent a novel target for NSCLC treatment. [ABSTRACT FROM AUTHOR]

This paper presents a new effective approach for the sensitive film deposition of surface acoustic wave (SAW) chemical sensors for detecting organophosphorus compounds such as O-ethyl-S-2-diisopropylaminoethyl methylphosphonothiolate (VX) containing sulfur at extremely low concentrations. To improve the adsorptive efficiency, a two-step technology is proposed for the sensitive film preparation on the SAW delay line utilizing gold electrodes. First, mono[6-deoxy-6-[(mercaptodecamethylene)thio]]-ß- cyclodextrin is chosen as the sensitive material for VX detection, and a ~2 nm-thick monolayer is formed on the SAW delay line by the binding of Au-S. This material is then analyzed by atomic force microscopy (AFM). Second, the VX molecule is used as the template for molecular imprinting. The template is then removed by washing the delay line with ethanol and distilled water, thereby producing the sensitive and selective material for VX detection. The performance of the developed SAW sensor is evaluated, and results show high sensitivity, low detection limit, and good linearity within the VX concentration of 0.15-5.8 mg/m³. The possible interactions between the film and VX are further discussed. [ABSTRACT FROM AUTHOR]

Background: The ulnar styloid is an important supportive structure for the triangular fibrocartilage complex. However, it remains inconclusive whether or not a fractured ulnar styloid should be fixed in an unstable distal radius fracture (DRF) with a stable distal radioulnar joint (DRUJ). The purpose of this study is to evaluate the effect of an untreated ulnar styloid fracture on the outcome of unstable DRF treated with transarticular external fixation when the DRUJ is stable. Methods: 106 patients with an unstable DRF and a stable DRUJ were included in this study following external fixation. The patients were divided into the non-fracture, the tip-fracture and the base-fracture groups according to the location of the ulnar styloid fracture at the time of injury. Postoperative evaluation included the range of wrist motion, the radiological index, the grip strength, the PRWE-HK scores, the wrist pain scores, and the instability of DRUJ at the external fixator removal time, three months postoperatively and the final follow-up visit. Results: The patients were followed for 12 to 24 months (15 months in average). Sixty-two of 106 patients (58%) had ulnar styloid fracture and 16 patients (26%) showed radiographic evidence of union of ulnar styloid fractures at the final follow-up visit. No significant difference in the radiological findings, the range of wrist motion, the grip strength, the PRWE-HK scores, and the wrist pain scores among three patient groups was detected at the external fixator removal time, three months postoperatively, or the final follow-up visit. Six of the 106 patients (5.7%) complained of persistent ulnar-side wrist pain during daily activities. One patient (0.9%) showed a positive sign in a stress-test, three patients (2.8%) showed a positive sign in a provocative-test, and five patients (4.7%) showed a positive sign in a press-test. There was no significant difference in the percentages of patients who complained of persistent ulnar-side wrist pain or showed a positive sign in the physical examination of the distal radioulnar joint among the three groups at the final follow-up time points. Conclusion: When the DRUJ is stable, an untreated ulnar styloid fracture does not affect the wrist outcome of the patient with an unstable DRF treated with external fixation. [ABSTRACT FROM AUTHOR]

Nanopores have become an important tool for molecule detection at single molecular level. With the development of fabrication technology, synthesized solid-state membranes are promising candidate substrates in respect of their exceptional robustness and controllable size and shape. Here, a 30--60 (tip-base) nm conical nanopore fabricated in 100 nm thick silicon nitride (Si3N4) membrane by focused ion beam (FIB) has been employed for the analysis of λ-DNA translocations at different voltage biases from 200 to 450 mV. The distributions of translocation time and current blockage, as well as the events frequencies as a function of voltage are investigated. Similar to previously published work, the presence and configurations of λ-DNA molecules are characterized, also, we find that greater applied voltages markedly increase the events rate, and stretch the coiled λ-DNA molecules into linear form. However, compared to 6--30 nm ultrathin solid-state nanopores, a threshold voltage of 181 mV is found to be necessary to drive DNA molecules through the nanopore due to conical shape and length of the pore. The speed is slowed down ∼5 times, while the capture radius is ∼2 fold larger. The results show that the large nanopore in thick membrane with an improved stability and throughput also has the ability to detect the molecules at a single molecular level, as well as slows down the velocity of molecules passing through the pore. This work will provide more motivations for the development of nanopores as a Multi-functional sensor for a wide range of biopolymers and nano materials. [ABSTRACT FROM AUTHOR]

Drought resistance is a complex quantitative trait, involving interactions of many metabolic pathways related to stress-resistant genes. Identification of a standard evaluation assay has been the most pressing problem for selection of drought-resistant genotypes and ultimately for elucidating the internal genetic mechanisms. A field phenotypic investigation was performed on more than 20 morphological traits and grain yield and its components for 201 Chinese common inbred maize (Zea mays L.) lines under water deficit in seven environments. An integrated selection criterion for drought resistance was proposed and used to identify drought-resistant maize genotypes. In it, six traits including grain yield, ear number per plant, kernel number per ear, plant height, anthesis-silking interval and degree of leaf curling were chosen as the most relevant factors related to drought resistance, as determined by statistical analysis. The integrated selection criterion was highly correlated with grain yield under both well-watered and water-stressed regimes, and was also highly correlated with other commonly used selection criteria. Moreover, for 128 (63.7%) inbred lines the evaluation result with this criterion was consistent across more than three environments thus avoiding the effect of genotype-environment interaction, though stress level between the different environments largely fluctuated. There were 43 inbred lines evaluated for drought-resistance and most were bred during 1990-2000. The criterion will be useful to identify excellent drought-resistant genotypes in future maize molecular breeding programs. [ABSTRACT FROM AUTHOR]

Protein crystals usually grow at a preferable temperature which is however not known for a new protein. This paper reports a new approach for determination of favorable crystallization temperature, which can be adopted to facilitate the crystallization screening process. By taking advantage of the correlation between the temperature dependence of the second virial coefficient (B22) and the solubility of protein, we measured the temperature dependence of B22 to predict the temperature dependence of the solubility. Using information about solubility versus temperature, a preferred crystallization temperature can be proposed. If B22 is a positive function of the temperature, a lower crystallization temperature is recommended; if B22 shows opposite behavior with respect to the temperature, a higher crystallization temperature is preferred. Otherwise, any temperature in the tested range can be used. [ABSTRACT FROM AUTHOR]

Maize is one of the most important food and feed crops in Asia, and is a source of income for several million farmers. Despite impressive progress made in the last few decades through conventional breeding in the “Asia-7” (China, India, Indonesia, Nepal, Philippines, Thailand, and Vietnam), average maize yields remain low and the demand is expected to increasingly exceed the production in the coming years. Molecular marker-assisted breeding is accelerating yield gains in USA and elsewhere, and offers tremendous potential for enhancing the productivity and value of Asian maize germplasm. We discuss the importance of such efforts in meeting the growing demand for maize in Asia, and provide examples of the recent use of molecular markers with respect to (i) DNA fingerprinting and genetic diversity analysis of maize germplasm (inbreds and landraces/OPVs), (ii) QTL analysis of important biotic and abiotic stresses, and (iii) marker-assisted selection (MAS) for maize improvement. We also highlight the constraints faced by research institutions wishing to adopt the available and emerging molecular technologies, and conclude that innovative models for resource-pooling and intellectual-property-respecting partnerships will be required for enhancing the level and scope of molecular marker-assisted breeding for maize improvement in Asia. Scientists must ensure that the tools of molecular marker-assisted breeding are focused on developing commercially viable cultivars, improved to ameliorate the most important constraints to maize production in Asia. [ABSTRACT FROM AUTHOR]

Acute promyelocytic leukemia (APL) is an aggressive disease that requires prompt treatment. Promyelocytic leukemia protein-retinoic acid receptor α (PML-RARα) fusion genes resulting from reciprocal translocation are considered a molecular basis for diagnosing APL. Moreover, PML-RARα fusion gene testing is an essential tool for monitoring the response to therapy via minimal residual disease and providing a diagnosis before rapid disease progression in APL. The present study developed a novel droplet digital PCR (ddPCR) assay to rapidly detect two PML-RARα variants (bcr1 and bcr3) and compared its limit of detection (LOD) with quantitative PCR (qPCR). It was demonstrated that the LOD of ddPCR for PML-RARα reached 0.001%, and the evaluation of high copy number samples of PML-RARα by ddPCR correlated well with qPCR. Furthermore, clinical sample testing with ddPCR found that 34 and 24% samples were bcr-1-positive and bcr3-positive, respectively. However, according to qPCR, 30% of the samples were bcr1-positive and 20% were bcr3-positive. In addition, the concordance rate between ddPCR and qPCR reaction was 86%. While monitoring minimal residual disease, the PML-RARα mutation rate of three patients who recovered well decreased to 0.34%. However, one patient who was bcr3-positive and relapsed had a mutation rate of 13% while in remission, indicating that the bcr3 isoform may be an adverse prognostic factor affecting recovery. Therefore, the present results suggested that this novel ddPCR assay may be useful for monitoring and evaluating the treatment effects and prognosis of APL. • DdPCR assay had rapidly detected two PML-RARα variants (bcr1 and bcr3). • The LOD of ddPCR for PML-RARα reached 0.001%. • The concordance rate between ddPCR and qPCR reaction was 86%. • bcr3 isoform may be an adverse prognostic factor affecting recovery. [ABSTRACT FROM AUTHOR]

Background: Endogenous α-synuclein (α-Syn) is involved in many pathophysiological processes in the secondary injury stage after acute spinal cord injury (SCI), and the mechanism governing these functions has not been thoroughly elucidated to date. This research aims to characterize the effect of α-Syn knockdown on transcriptional levels after SCI and to determine the mechanisms underlying α-Syn activity based on RNA-seq. Result: The establishment of a rat model of lentiviral vector-mediated knockdown of α-Syn in Sprague-Dawley rats with T3 spinal cord contusion (LV_SCI group). The results of the RNA-seq analysis showed that there were 337 differentially expressed genes (DEGs) between the SCI group and the LV_SCI group, and 153 DEGs specific to LV_SCI between the (SCI vs LV_SCI) and (SCI vs CON) comparisons. The top 20 biological transition terms were identified by Gene ontology (GO) analysis. The Kyoto Gene and Genomic Encyclopedia (KEGG) analysis showed that the LV_SCI group significantly upregulated the cholinergic synaptic & nicotine addiction and the neuroactive ligand receptor interaction signaling pathway. Enriched chord analysis analyzes key genes. Further cluster analysis, gene and protein interaction network analysis and RT-qPCR results showed that Chrm2 and Chrnb2 together significantly in both pathways. The proliferation of muscarinic cholinergic receptor subtype 2 (Chrm2) and nicotinic cholinergic receptor subtype β2 (Chrnb2), and the neurogenesis were elevated in the injury site of LV_SCI group by immunofluorescence. Further by subcellular localization, the LV_SCI group enhanced the expression of Chrnb2 at the cell membrane. Conclusion: Knockdown of α-Syn after SCI enhance motor function and promote neurogenesis probably through enhancing cholinergic signaling pathways and neuroreceptor interactions. This study not only further clarifies the understanding of the mechanism of knockdown of α-Syn on SCI but also helps to guide the treatment strategy for SCI. [ABSTRACT FROM AUTHOR]