Search

Abstract: TEM-1 β-lactamase confers bacterial resistance to penicillin antibiotics and has acquired mutations that permit the enzyme to hydrolyze extended-spectrum cephalosporins or to avoid inactivation by β-lactamase inhibitors. However, many of these substitutions have been shown to reduce activity against penicillin antibiotics and/or result in loss of stability for the enzyme. In order to gain more information concerning the tradeoffs associated with active site substitutions, a genetic selection was used to find second site mutations that partially restore ampicillin resistance levels conferred by an R244A active site TEM-1 β-lactamase mutant. An L201P substitution distant from the active site that enhanced ampicillin resistance levels and increased protein expression levels of the R244A TEM-1 mutant was identified. The L201P substitution also increases the ampicillin resistance levels and restores expression levels of a poorly expressed TEM-1 mutant with a core-disrupting substitution. In vitro thermal denaturation of purified protein indicated that the L201P mutation increases the T m value of the TEM-1 enzyme. The X-ray structure of the L201P TEM-1 mutant was determined to gain insight into the increase in enzyme stability. The proline substitution occurs at the N-terminus of an α-helix and may stabilize the enzyme by reducing the helix dipole, as well as by lowering the conformational entropy cost of folding due to the reduced number of conformations available in the unfolded state. Collectively, the data suggest that L201P promotes tolerance of some deleterious TEM-1 mutations by enhancing the protein stability of these mutants. [Copyright &y& Elsevier]

Aim: Methane oxidation driven by soil aerobic methanotrophs exhibits the largest methane sink capacity in forest ecosystems and plays important roles in the alleviation of global warming. Many studies have revealed the distribution of methanotrophs in forest ecosystems at field scales; however, the biogeographical patterns of methanotrophic communities and related ecological processes and the drivers shaping methanotrophic communities at a large scale remain poorly understood. Location: China's forests. Time period: 2012–2013. Major taxa studied: Methanotrophic communities. Methods: We evaluated the geographical distributions of soil methanotrophic communities across 26 forests along a 4,000‐km north–south transect in China using a MiSeq high‐throughput sequencing technique. The assembly processes and drivers of the methanotrophic communities were evaluated using the phylogenetic null model approach and structural equation modelling, respectively. Results: The results showed that the upland soil cluster α (USCα) and ammonia‐ oxidizing bacteria‐related (AOB‐rel) methanotrophs were the most abundant taxa in forest soils and exhibited contrasting distributions of relative abundance across different climate zones, suggesting that they occupy different environmental niches. The α‐diversity pattern of the soil methanotrophic community followed a hump‐shaped pattern along a large latitudinal gradient. Statistical analyses suggest that aridity and vegetation productivity [here represented with the normalized difference vegetation index (NDVI)] are major drivers of the α‐diversity of the methanotrophic community, whereas soil pH is the key environmental factor shaping the β‐diversity of the methanotrophic community at a large scale. Additionally, the community assembly of the methanotrophs primarily resulted from deterministic processes, among which heterogeneous selection had a greater contribution in shaping the methanotrophic community than homogeneous selection. Main conclusions: Our study provides new insights into the biogeographical distributions, assembly processes and ecological predictors of the methanotrophic community in forest soil at a large scale. These results can be used to improve simulation models for the better prediction of ecosystem functions under predicted global changes. [ABSTRACT FROM AUTHOR]

Digoxin (DIG) is a positive inotropic drug with a narrow therapeutic window that is used in the clinic for heart failure. The active efflux transporter of DIG, P-glycoprotein (P-gp), mediates DIG absorption and excretion in rats and humans. Up to date, several studies have shown that the ginger and Poria extracts in Zhenwu Tang (ZWT) affect P-gp transport activity. This study aimed to explore the effects of ZWT on the tissue distribution and pharmacokinetics of DIG in rats. The deionized water or ZWT (18.75 g/kg) was orally administered to male Sprague–Dawley rats once a day for 14 days as a pretreatment. On day 15, 1 hour after receiving deionized water or ZWT, the rats were given the solution of DIG at 0.045 mg/kg dose, and the collection of blood samples was carried out from the fundus vein or excised tissues at various time points. HPLC-MS/MS was used for the determination of the DIG concentrations in the plasma and the tissues under investigation. The pharmacokinetic interactions between DIG and ZWT after oral coadministration in rats revealed significant reductions in DIG Cmax and AUC0-∞, as well as significant increases in T1/2 and MRT0-∞. When coadministered with ZWT, the DIG concentration in four of the investigated tissues statistically decreased at different time points except for the stomach. This study found that combining DIG with ZWT reduced not only DIG plasma exposure but also DIG accumulation in tissues (heart, liver, lungs, and kidneys). The findings of our study could help to improve the drug's validity and safety in clinical applications and provide a pharmacological basis for the combined use of DIG and ZWT. [ABSTRACT FROM AUTHOR]

Radiation measurement at underwater environment helps to get a better understanding on sedimentation, geological structure, radiation monitoring, and so on. However, reports about radiation of natural underwater environment are rare, especially in situ gamma radiation measurement. Two gamma spectrometers are going to be used in underwater in situ radiation measurement. Aiming at different scientific goals, the spectrometers can develop multiple kinds of measurements, including dose and energy spectrum of gamma rays. In this article, a compatible data acquisition (DAQ) system is proposed. The DAQ provides features of readout, visualization, data process algorithm, and file input and output. To benefit from high reusability and low coupling, the Model-View-ViewModel (MVVM) pattern is adopted in the DAQ system. With an application layer protocol based on Modbus, the DAQ can be fully compatible with different spectrometers. Besides supporting of real-time control, the DAQ system also provides a way to program the spectrometers to execute an unmanned mission, so that the spectrometers can load a timetable from a built-in flash memory and run automatically. [ABSTRACT FROM AUTHOR]

Bat algorithm has disadvantages of slow convergence rate, low convergence precision and weak stability. In this paper, we designed an improved bat algorithm with a logarithmic decreasing strategy and Cauchy disturbance. In order to meet the requirements of global optimal and dynamic obstacle avoidance in path planning for a mobile robot, we combined bat algorithm (BA) and dynamic window approach (DWA). An undirected weighted graph is constructed by setting virtual points, which provide path switch strategies for the robot. The simulation results show that the improved bat algorithm is better than the particle swarm optimization algorithm (PSO) and basic bat algorithm in terms of the optimal solution. Hybrid path planning methods can significantly reduce the path length compared with the dynamic window approach. Path switch strategy is proved effective in our simulations. [ABSTRACT FROM AUTHOR]

Capacitor with high energy density, wide operating temperature range, large power density and environmental friendliness is strongly demanded in modern electrical and electronic devices. In this work, Bi 2 Zn 2/3 Nb 4/3 O 7 (BZN) thin film as a novel lead-free material with ultra-high energy storage density and ultra-wide operating temperature range, is prepared by magnetron sputtering. Dielectric properties and electric breakdown strength depend on the substrate temperature, resulting in the change of energy storage performance. The dielectric constant and breakdown strength reach respectively 182 and 3.81 MV/cm for the BZN thin film prepared at 700 °C, while the maximum recoverable energy storage density (63.5 J/cm3) at 100 Hz is achieved. Moreover, the BZN thin films possess excellent thermal stability of energy storage properties in an ultra-wide temperature range (-150- 250 °C) and strong fatigue endurance after 1 × 106 charge–discharge cycles. These results reveal that the BZN thin film can be a promising candidate for lead-free energy storage application in equipment working in harsh environment. • The BZN films show an ultrahigh energy storage density of 63.5 J/cm3. • The BZN films exhibit excellent performance stability in -150- 250 °C. • The BZN films show strong fatigue endurance after 1 × 106 charge–discharge cycles. • BZN films have a high power density (53.92 MW/cm3). [ABSTRACT FROM AUTHOR]

Because of high transparency, conductivity and flexibility, silver nanowire (AgNW) networks have been widely explored as a promising alternative to indium tin oxide (ITO). However, their poor adhesiveness, corrosion and thermal stability still remain limiting factors for widespread adoption in a range of devices. Here, we introduce SnO 2 to improve the adhesion and stability performances of AgNWs by controlling the preparation process, enhance the conductivity by providing the electric channels at contacts of AgNWs. The unique structural feature of composite film allows for a novel transparent conductor with low sheet resistance of 7.9 Ω/sq. and high transmittance of 87.6% (at 550 nm), as well as good flexibility. Unlike bare AgNW networks, the composite film retains its original conductivity under immersion in HCl and Na 2 S solutions, or long-term storage at up to 85% relative humidity at 85 °C. This chemical durability can be attributed to the absence of silver corrosion products for the AgNW encapsulated by SnO 2. Furthermore the resistance is nearly unchanged after tape and ultrasonication tests, indicating a good adhesion to the substrate. Finally, a flexible transparent heater employing a hybrid film is realized. [ABSTRACT FROM AUTHOR]

At present, remote sensing (RS) is applied in detecting vehicle exhaust emissions, and usually the RS emission results in a definite vehicle specific power (VSP) range are used to evaluate vehicle emissions and identify high-emitting vehicles. When the VSP exceeds this range, the corresponding vehicle emission RS data will not be used to assess vehicle emissions. This method is equivalent to setting only one VSP Bin qualified for vehicle emission evaluation, and generally only one threshold limit is given for each emission pollutant without considering the fluctuation characteristics of vehicle emissions with VSP. Therefore, it is easy to cause misjudgment in identifying high-emitting vehicles and is not conducive to scientific management of vehicle emissions. In addition, the vehicle emissions outside the selected VSP Bin are more serious and should be included in the scope of supervision. This research proposed the methods of vehicle classifications and VSP Binning in order to categorize the driving conditions of each kind of vehicles, and a big data approach was proposed to analyze the vehicle emission RS data in each VSP Bin for vehicle emission evaluation. [ABSTRACT FROM AUTHOR]

In situ radioactivity measurements in a deep ocean environment are essential for marine environmental pollution monitoring and seabed geological exploration. In the past, the most widely used gamma spectrometers were based on towed instrumentation, which could only be operated underwater at a depth of less than 1500 m. In this study, a compact gamma spectrometer with small-size, light weight, and low power consumption was designed for working in a marine in situ environment. This spectrometer, with two essential parts: detector and electronics, was designed to work on different underwater platforms in the real-time control mode or autonomous operation mode. Multiple small volume avalanche photodiodes were coupled with NaI(Tl), which can significantly reduce the spectrometer volume compared with the option of the photomultiplier tube. Integrated readout electronics were employed to digitize all detector signals for miniaturization and low power consumption. The field programmable gate array (FPGA) was used to obtain the energy spectrum in real-time and an online multi-channel summation with temperature calibration algorithm was employed to improve detection efficiency. Relevant tests were also conducted in the laboratory to evaluate critical techniques and system performance. Results show that the energy resolution (full width at half maximum over the peak position) was ∼7.5% at 662 keV, verifying the online multi-channel summation with temperature calibration based on the FPGA. Moreover, the compact prototype spectrometer worked well in the power-on hydraulic test. [ABSTRACT FROM AUTHOR]

Background: A combination of programmed cell death protein‐1 (PD‐1)/programmed cell death ligand‐1 (PD‐L1) inhibitors and radiotherapy (RT) is increasingly being used to treat non‐small‐cell lung cancer (NSCLC). However, the safety and efficacy of this approach remains controversial. We performed a systematic review and meta‐analysis to summarize the related research. Methods: We searched the China Biology Medicine, EMBASE, Cochrane Library, and PubMed databases for all the relevant studies. The Stata software, version 12.0 was used for the meta‐analysis. Results: The study included 20 clinical trials that enrolled 2027 patients with NSCLC. Compared with non‐combination therapy, combination therapy using PD‐1/PD‐L1 inhibitors and RT was associated with prolonged overall survival (OS) (1‐year OS: odds ratio [OR] 1.77, 95% confidence interval [CI] 1.35–2.33, p = 0.000; 2‐year OS: OR 1.77, 95% CI 1.35–2.33, p = 0.000) and progression‐free survival (PFS) (0.5‐year PFS: OR 1.83, 95% CI 1.13–2.98, p = 0.014; 1‐year PFS: OR 2.09, 95% CI 1.29–3.38, p = 0.003; 2‐year PFS: OR 2.47, 95% CI 1.13–5.37, p = 0.023). Combination therapy also improved the objective response rate (OR 2.76, 95% CI 1.06–7.19, p = 0.038) and disease control rate (OR 1.80, 95% CI 1.21–2.68, p = 0.004). This meta‐analysis showed that compared with non‐combination therapy, combination therapy using PD‐1/PD‐L1 inhibitors and RT did not increase the serious adverse event rates (≥grade 3); however, this approach increased the rate of grade 1–2 immune‐related or radiation pneumonitis. Subgroup analyses revealed that the sequence of PD‐1/PD‐L1 inhibitors followed RT outperformed in which concurrent PD‐1/PD‐L1 inhibitor and RT followed PD‐1/PD‐L1 inhibitor. Combination of stereotactic body RT or stereotactic radiosurgery with PD‐1/PD‐L1 inhibitors may be more effective than a combination of conventional RT with PD‐1/PD‐L1 inhibitors in patients with advanced NSCLC. Conclusion: Combination therapy using PD‐1/PD‐L1 inhibitors and RT may improve OS, PFS, and tumor response rates without an increase in serious adverse events in patients with advanced NSCLC. However, combination therapy was shown to increase the incidence of mild pneumonitis. [ABSTRACT FROM AUTHOR]

The effect of gamma (γ)-irradiation on AlGaN-based light-emitting diodes (LEDs) in the short-wavelength ultraviolet (UVC, 210–280 nm) spectral range under electrical stress is characterized by electroluminescence and current–voltage measurement. Different from previous reports that γ-irradiation can hardly damage nitride devices, we observe that the optical power decreases and leakage current increases obviously after electrical stress under γ-irradiation. To delve into the nature of degradation, variation of defects is studied using temperature-dependent low-frequency noise measurement. After stress, the ~0.78-eV defects attributed to N antisite are generated and lead to device degradation, which is accompanied by a reduction of the intrinsic Ga vacancy with an energy level of ~0.38 eV. The variation of defects after stress in γ-irradiated environment is more evident than that in nonirradiated environment, which is well corresponding to the performance degradation behavior. In conclusion, γ-irradiation is found to accelerate degradation induced by electrical stress, and the study can help improve irradiation resistance in AlGaN-based UVC LEDs. [ABSTRACT FROM AUTHOR]

The combination of carbon ion radiotherapy and anti-PD-1 antibody represents a new approach to treating thoracic tumors. However, the lung damage caused by this combination therapy may limit its use, and the potential mechanisms for this are worthy of investigation. The objective of this research was to examine the potential involvement of repulsive guidance molecule b (RGMb) in lung damage promoted by the utilization of carbon ion irradiation combined with an anti-PD-1 antibody. The C57BL/6 mice have been randomly separated into four distinct groups: control, anti-PD-1, whole thorax carbon ion irradiation, and irradiation in combination with anti-PD-1 treatment groups (combination group). Detection of pathological changes in lung tissue using HE staining. Detection of pulmonary fibrosis by Masson staining and the hydroxyproline assay. ELISA to detect TNF-α, TGF-β, IL-6, and IL-1β expression levels within lung homogenates. The expression of RGMb, p38 MAPK, and Erk1/2 pathways was detected using a fully automated digital Western blotting system WES (ProteinSimple, USA). Flow cytometry was employed to analyze tissue-resident memory T cells (TRM) within the lung. Subsequently, the siRNA gene was employed to induce the downregulation of RGMb in mice in order to validate the involvement of RGMb in radiation-immune lung injury. The present study observed a significant increase in both inflammatory and fibrotic indicators within the mice group's lung tissue that received the combination treatment. The combination group exhibited elevated levels of TGF-β, TNF-α, IL-6, and IL-1β in lung homogenates. Anti-PD-1 antibody and carbon ion irradiation, upregulated RGMb, phospho-p38 MAPK and phospho-Erk1/2. The results obtained from the flow cytometry analysis indicated that the combination group was significantly higher in the number of clonal expansion TRMs, which were predominantly characterized by the expression of CD8+CD103+CD69-TRMs. The downregulate of RGMb via siRNA in mice resulted in a decrease in phospho-p38 MAPK and phospho-Erk1/2. The combination group exhibited a reduction in TNF-α, TGF-β, IL-6, and IL-1β in their lung tissues, and the number of CD8+CD103+CD69-TRM was significantly reduced. The combination group exhibited a significant improvement in inflammatory and fibrotic indicators within the lung tissues. Anti-PD-1 antibody and carbon ion irradiation synergistically regulate RGMb, leading to strong clonal expansion of lung TRM through the p38 MAPK and Erk1/2 pathways. The present study offers valuable insights into the treatment of lung injury due to the combined administration of carbon ion radiotherapy and anti-PD-1 antibody therapy. • Explored the mechanisms of lung damage promoted by carbon ions combined with anti-PD-1 antibodies. • Anti-PD-1 antibody and carbon ions regulate RGMb, leading to clonal expansion of TRM through p38 MAPK and Erk1/2 pathways. • The combination group was higher in the number of clonal expansion CD8+CD103+CD69-TRMs. • Offers insights into the treatment of lung injury due to combined administration of carbon ions and anti-PD-1 antibodies. [ABSTRACT FROM AUTHOR]

Food microstructure design has become an important research area in artificial food manufacturing. The fibrous structure is one of the most critical elements since it is the fundamental building blocks constructing the structure of several important food matrices. However, at present, edible fibers at nanoscale are seldomly successfully manufactured due to technical difficulties when only food-grade materials are allowed to be used. In the current study, edible nanofiber consisting of a single component of safflower seed meal protein (SMP) was prepared based on a three-step protocol consisting of electrostatic spinning, protein-cinnamaldehyde cross-linking, and subsequent immersion in the citric acid buffer to remove none-protein components. Addition of pullulan (PUL) to SMP during electrospinning facilitated fibrous structure formation. Results of SEM demonstrated that SMP: PUL = 5:5 with combined ratio 20% (w/v) in water is the upper limit to obtain well-structured composite nanofiber with no addition of Tween 80. In the second step, protein-cinnamaldehyde cross-linking was implemented to stabilize the structure of SMP. In the last step, citric acid buffer with pH4.6 was used to remove pullulan residues and thereafter nanofibers with porous surfaces composed of only SMP were successfully obtained. Our results showed that SMP single-component nanofibers had high thermal stability and good water-holding capacity, and thus suggesting that electrospinning can be a potentially innovative strategy to manufacture food fibrous microstructures especially at nanoscale. [Display omitted] • A feasible strategy for preparation of edible plant protein-based nanofibers is presented. • Safflower seed meal protein (SMP) is used as raw material for electrostatic spinning firstly. • Pullulan is used as spinning aid but can be eliminated afterwards by acid-immersion technique. • SMP becomes water-insoluble by being cross-linked with cinnamaldehyde. • Porous structure improves the water-holding capacity of electrostatic-spun nanofibers. [ABSTRACT FROM AUTHOR]

Background: Osteosarcoma is a rare malignant bone tumor in adolescents and children. Poor prognosis has always been a difficult problem for patients with osteosarcoma. Recent studies have shown that tumor infiltrating immune cells (TIICs) are associated with the clinical outcome of osteosarcoma patients. The aim of our research was to construct a risk score model based on TIICs to predict the prognosis of patients with osteosarcoma.Methods: CIBERSORTX algorithm was used to calculate the proportion of 22 TIIC types in osteosarcoma samples. Kaplan-Meier curves were drawn to investigate the prognostic value of 22 TIIC types. Forward stepwise approach was used to screen a minimal set of immune cell types. Multivariate Cox PHR analysis was performed to construct an immune risk score model.Results: Osteosarcoma samples with CIBERSORTX output p value less than 0.05 were selected for research. Kaplan-Meier curves indicated that naive B cells (p = 0.047) and Monocytes (p = 0.03) in osteosarcoma are associated with poor prognosis. An immune risk score model was constructed base on eight immune cell types, and the ROC curve showed that the immune risk score model is reliable in predicting the prognosis of patients with osteosarcoma (AUC = 0.724). Besides, a nomogram model base on eight immune cell types was constructed to predict the survival rate of patients with osteosarcoma.Conclusions: TIICs are closely related to the prognosis of osteosarcoma. The immune risk score model based on TIICs is reliable in predicting the prognosis of osteosarcoma. [ABSTRACT FROM AUTHOR]

Background: This study's initial results revealed significant decreases in treatment‐related esophagitis and pneumonitis cases in patients with thoracic esophageal squamous cell carcinoma (ESCC) treated with involved‐field irradiation (IFI), compared to elective nodal irradiation (ENI). This report outlines the long‐term trial results, specifically; overall survival (OS), progression‐free survival (PFS), metastasis‐free survival (MFS), and locoregional progression‐free survival (LRFS). Materials and Methods: Stage II–III thoracic ESCC patients were assigned randomly, in a 1:1 ratio, into either the ENI or IFI arm. Radiation therapy was delivered once a day in 1.8‐2.0 Gy fractions to a total dose of 60.0‐66.0 Gy to the gross tumor volume and 50.0‐54.0 Gy to the clinical target volume. The primary endpoints were acute treatment‐related esophagitis and pneumonitis. The results for the primary endpoints were previously published in 2018. In this article, we analyzed the secondary endpoints including PFS, LRFS, MFS, and OS. Results: Between April 2012 and October 2016, 228 patients from nine participating centers in China were enrolled into this study and randomly assigned to two treatment groups. For ENI and IFI groups, respectively, the results showed similarity and were as follows: median PFS (20.3 months vs 21.4 months), OS (32.5 months vs 34.9 months), MFS (28.2 months vs 26.0 months), and LRFS (25.0 months vs 26.6 months). In particular, respective OS rates in the ENI and IFI groups were 84.6% and 82.5% after 1 year, 45.1% and 48.7% after 3 years, and 29.8% and 30.7% at 5 years. PFS rates after 1, 3, and 5 years were 58.9%, 34.2%, and 26.9%, respectively, in the ENI arm compared to 64.4%, 30.8%, and 27.7%, respectively, in the IFI arm. Multivariate analysis identified clinical stage and tumor responses as independent predictors of OS. Meanwhile, tumor location, cStage, and tumor response were identified as independent factors influencing PFS. Conclusion: IFI was associated with similar survival as ENI in patients with thoracic ESCC, suggesting that IFI is an acceptable treatment method for thoracic ESCC. [ABSTRACT FROM AUTHOR]

Porcelain that contains micrometer-sized ε-Fe 2 O 3 , a promising advanced material with unique magnetic properties, has received growing attention these years. Herein, we discovered millimeter-sized unprecedented mullite-ε-Fe 2 O 3 clusters organized in a flower-like manner blooming on the Hare's Fur Jian ware of the Song dynasty (960–1279 A.D.). They are composed of branches radiating from the center, petals growing along the branches, needles on both sides of the petals and reflective platforms distributed all over the flower. After a series of microscopic and spectroscopic characterizations, mullite and ε-Fe 2 O 3 were identified to be the main components, and a possible growth process was proposed. The residual quartz in the glaze, the relatively thin glaze on the edge of the bowl and the reducing firing environment were considered to be the main factors for its formation. These results provide a novel access toward the ancient ceramic technologies and inspirations on refractory mullite and magnetic material ε-Fe 2 O 3. [ABSTRACT FROM AUTHOR]

Background: Controversy persists about whether additional induction chemotherapy (ICT) before neoadjuvant chemoradiation (NCRT) yields improved oncological outcomes. We performed a systematic review and meta-analysis to compare ICT+ NCRT+ surgery(S) with NCRT+ S in patients with locally advanced rectal cancer (LARC). Methods: We searched the PubMed, EMBASE, Cochrane Library, and China Biology Medicine (CBM) databases. The data were analyzed with Stata version 12.0 software. Results: We identified 9 relevant trials that enrolled 1538 patients. We detected no significant difference in the 5-year overall survival (OS) (OR 1.50, 95% CI 0.48–4.64), disease-free survival (DFS) (OR 1.03, 95% CI 0.73–1.46), local recurrence (LR) (OR 0.80, 95% CI 0.45–1.43), and distant metastasis (DM) rates (OR 1.03, 95% CI 0.55–1.93) between patients who did and did not receive ICT. The addition of ICT before NCRT had a similar pathological complete response rate compared to NCRT (OR 1.26, 95% CI 0.90–1.77). Our findings suggest that between the ICT + NCRT+S and NCRT+S groups, ICT improved the incidence of grade 3 to 4 toxicity effects (OR 4.81, 95% CI 2.38–9.37), but between the ICT + NCRT+S and NCRT+S+ adjuvant chemotherapy (ACT) groups, ICT might reduce toxicity (OR 0.19, 95% CI 0.08–0.50). ICT had no significant impact on surgical complications (OR 0.97, 95% CI 0.63–1.51). Conclusions: The addition of ICT before NCRT seemingly shows no survival benefit on patients with LARC, and might increase the toxicity. [ABSTRACT FROM AUTHOR]

Malignant melanomas (MMs) were the fifth most common cancer in men and the sixth most common cancer in women in 2018, respectively. These are characterized by high metastatic rates and poor prognoses. We systematically reviewed safety and efficacy of carbon‐ion radiotherapy (CIRT) for treating MMs. Eleven studies were eligible for review, and the data showed that MM patients showed better local control with low recurrence and mild toxicities after CIRT. Survival rates were slightly higher in patients with cutaneous or uveal MMs than in those with mucosal MMs. CIRT in combination with chemotherapy produced higher progression‐free survival rates than CIRT only. In younger patients, higher rates of distant metastases of gynecological MMs were observed. The data indicated that CIRT is effective and safe for treating MMs; however, a combination with systemic therapy is recommended to ensure the best possible prognosis for MMs. [ABSTRACT FROM AUTHOR]

Differentiating malignant from benign ascites often leads to confusion and an inability to exclude its multitude of causes in many patients. In the present study, T lymphocyte subsets and DNA ploidy in ascitic fluid were detected by flow cytometer. There were significant differences in T lymphocyte subsets between benign and malignant ascites. For malignant ascites, the sensitivity of DNA aneuploid is 75.6%, the specificity is 79.0%, and the accuracy is 77.6%. The results demonstrate that T lymphocyte subsets determination and DNA ploidy analysis can be used in the differential diagnosis between benign and malignant ascites. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of a young systemic environment and growth differentiation factor 11 (GDF‐11) on aging cartilage. Methods: A heterochronic parabiosis model (2‐month‐old mouse and 12‐month‐old mouse [Y/O]), an isochronic parabiosis model (12‐month‐old mouse and 12‐month‐old mouse [O/O]), and 12‐month‐old mice alone (O) were evaluated. Knee joints and chondrocytes from old mice were examined by radiography, histology, cell proliferation assays, immunohistochemistry, Western blotting, and quantitative reverse transcriptase–polymerase chain reaction 16 weeks after parabiosis surgery. GDF‐11 was injected into 12‐month‐old mouse joints daily for 16 weeks. Cartilage degeneration, cell proliferation, and osteoarthritis‐related gene expression were evaluated. Results: Osteoarthritis Research Society International scores in old mice were significantly lower in the Y/O group than in the O/O and O groups (both P < 0.05). The percentage of 5‐ethynyl‐2′‐deoxyuridine–positive chondrocytes in old mice was significantly higher in the Y/O group than in the other groups (P < 0.05). Type II collagen (CII) and SOX9 messenger RNA levels differed in cartilage from old mice in the Y/O group compared to the O/O and O groups (both P < 0.05). RUNX‐2, CX, and matrix metalloproteinase 13 levels were significantly lower in cartilage from old mice in the Y/O group compared to the O/O and O groups (both P < 0.05). Similar results were obtained for protein expression levels and after GDF‐11 treatment in vitro and in vivo. Phosphorylated Smad2/3 (pSmad2/3) levels were higher in the recombinant GDF‐11–treated group than in the control group. Conclusion: A young systemic environment promotes chondrocyte proliferation and cartilage matrix synthesis in old mice. GDF‐11, a "young factor," contributes to these effects through the up‐regulation of pSmad2/3. [ABSTRACT FROM AUTHOR]

We investigate the asymptotic behavior of a class of non-autonomous stochastic FitzHugh–Nagumo systems driven by additive white noise on unbounded thin domains. For this aim, we first show the existence and uniqueness of random attractors for the considered equations and their limit equations. Then, we establish the upper semicontinuity of these attractors when the thin domains collapse into a lower-dimensional unbounded domain. [ABSTRACT FROM AUTHOR]

The outbreak of a novel corona Virus Disease 2019 (COVID-19) in the city of Wuhan, China has resulted in more than 1.7 million laboratory confirmed cases all over the world. Recent studies showed that SARS-CoV-2 was likely originated from bats, but its intermediate hosts are still largely unknown. In this study, we assembled the complete genome of a coronavirus identified in 3 sick Malayan pangolins. The molecular and phylogenetic analyses showed that this pangolin coronavirus (pangolin-CoV-2020) is genetically related to the SARS-CoV-2 as well as a group of bat coronaviruses but do not support the SARS-CoV-2 emerged directly from the pangolin-CoV-2020. Our study suggests that pangolins are natural hosts of Betacoronaviruses. Large surveillance of coronaviruses in pangolins could improve our understanding of the spectrum of coronaviruses in pangolins. In addition to conservation of wildlife, minimizing the exposures of humans to wildlife will be important to reduce the spillover risks of coronaviruses from wild animals to humans. Author summary: Recently, a novel coronavirus, SARS-CoV-2, caused a still ongoing pandemic. Epidemiological study suggested this virus was associated with a wet market in Wuhan, China. However, the exact source of this virus is still unknown. In this study, we attempted to assemble the complete genome of a coronavirus identified from two groups of sick Malayan pangolins, which were likely to be smuggled for black market trade. The molecular and evolutionary analyses showed that this pangolin coronavirus we assembled was genetically associated with the SARS-CoV-2 but was not likely its precursor. This study suggested that pangolins are natural hosts of coronaviruses. Determining the spectrum of coronaviruses in pangolins can help understand the natural history of coronaviruses in wildlife and at the animal-human interface, and facilitate the prevention and control of coronavirus-associated emerging diseases. [ABSTRACT FROM AUTHOR]

Background: Circular RNAs (circRNAs) play vital roles in the modulation of tumor progression. This study explored the biological functions of circ_0001105 in the progression of osteosarcoma (OS). Methods: qRT-PCR and in situ hybridization (ISH) were performed to detect the expression status of circ_0001105 in cells and tissues. Bioinformatics analysis, dual-luciferase reporter gene assay, Western blot and qRT-PCR were performed to determine the relationships among RNAs. The CCK-8, colony formation, EdU, transwell and wound healing assays were conducted to evaluate the cell growth, invasion and migration of OS cells. Tumor xenografts were established to investigate the effects of circ_0001105 on tumor growth in vivo. Lastly, the protein expression of YTHDF2 in OS tissues was measured using immunohistochemical staining. Results: Data showed that circ_0001105 and YTHDF2 were significantly lower, while miR-766 was higher in OS tissues compared to adjacent tissues. Low expression of circ_0001105 or YTHDF2 was associated with poor survival of OS patients as demonstrated by the Kaplan-Meier analysis. In addition, miR-766 was identified as a direct binding target of circ_0001105 and YTHDF2. Ectopic overexpression of circ_0001105 or YTHDF2 significantly suppressed OS cell viability and invasion through regulating miR-766. Last, overexpression of circ_0001105 significantly attenuated in vivo tumor growth. Conclusion: Our findings suggest that circ_0001105 inhibits OS progression, at least partially, by regulating miR-766/YTHDF2 signaling pathway. [ABSTRACT FROM AUTHOR]

• The heat transfer characteristics of supercritical CO 2 are studied experimentally. • The mechanism of heat transfer deterioration is analyzed. • Two buoyancy criteria are assessed and compared. • A new heat transfer correlation with a buoyancy parameter is proposed. This study experimentally investigates the effect of buoyancy on the heat transfer characteristics of supercritical CO 2 in a vertical tube of 7.74 mm inner diameter. The experiments are performed for inlet temperatures ranging from 14 to 33 °C, pressure from 7.8 to 10 MPa, heat flux from 29.0 to 60.3 kW/m2, and mass flux from 138.3 to 512.1 kg/m2·s. The influences of heat flux, mass flux, pressure, inlet temperature, and flow direction on the heat transfer are analyzed with an emphasis on the buoyancy effect. The results show there is only one wall temperature peak at moderate heat flux and two peaks at high heat flux. The heat transfer under different mass fluxes is completely different due to the buoyancy effect. Current experimental data differ significantly from widely used empirical correlations. Therefore, a new correlation with a buoyancy parameter is developed, which provides better prediction accuracy of the Nussult number. [ABSTRACT FROM AUTHOR]

Of note, both the I Nature i [[3]] and I PLOS Pathogens i [[1]] articles reported 90.3% whole genome sequence identity between pangolin coronavirus and SARS-CoV-2. Contig k141 8467 flag = 1 multi = 6.0000 len = 345 did not align to the pangolin SARS-CoV-2 genome obtained in this study [[1]], and so it was not used in the reported genome assembly. [Extracted from the article]

Oesophageal cancer is a serious disease worldwide. In China, the incidence of esophageal cancer was reported to be ~478,000 in 2015. In the same year, the incidence of esophageal cancer in the United States was ~16,910. Radiotherapy serves as an important tool in the treatment of oesophageal cancer, and although radiation therapy has progressed over time, the prognosis of the majority of patients with oesophageal cancer remains poor. Additionally, the sensitivity of patients with oesophageal cancer to radiotherapy and chemotherapy is not yet clear. Although there are a number of studies on the radiosensitivity of oesophageal cancer cell lines, the vastly different results from different cell lines make them unreliable to use as a guide in clinical practice. Therefore, a common radiosensitive gene signature may provide more reliable results, and using different combinations of common gene signatures to predict the outcome of patients with oesophageal cancer may generate a unique gene signature in oesophageal cancer. In the present study, the radiosensitive index and prognostic index were calculated to predict clinical outcomes. The prognostic index of a 41-gene signature combination is the largest combination of gene signatures used for classifying oesophageal cancer patients into radiosensitive (RS) and radioresistance (RR) groups, to the best of our knowledge, and this gene signature was more effective in patients classified as having Stage III oesophageal cancer. Furthermore, four genes (carbonyl reductase 1, serine/threonine kinase PAK2, ras-related protein Rab 13 and twinfilin-1) may be sufficient to classify patients into either RS or RR. Subsequent to gene enrichment analysis, the cell communication pathway was significantly different between RS and RR groups in oesophageal cancer. These results may provide useful insights in improving radiotherapy strategies in clinical decisions. [ABSTRACT FROM AUTHOR]

Due to inherent high reliability and low maintenance cost, the brushless doubly fed induction generator (BDFIG) has become a promising candidate in offshore wind energy generation systems and dc/ac/hybrid microgrids. This paper proposes a novel BDFIG based system targeting at dc power generation (BDFIG-DC), which features interfacing the power winding (PW) and the dc grid through an uncontrolled rectifier and common dc link. Compared to conventional BDFIG systems fed by ac grid, the BDFIG-DC system offers an alternative to integrate the BDFIG into the dc transmission system with a simpler structure and lower cost. Due to the constraint imposed by the dc-side diode bridge, torque ripple reduction emerges as an urgent issue as a result of the distorted flux and current. To achieve the smooth dc-connected operation of the BDFIG, an improved vector control strategy is proposed in this paper, where the control of the system is divided into three parts: torque ripple reduction, frequency regulation, and average torque control. Based on the investigations into the electromagnetic torque reduction and small-signal model of the PW flux linkage, average torque and PW frequency are successfully controlled with torque ripple effectively suppressed. The effectiveness of the proposed system, along with the associated control strategy, is validated by the experimental results of a 10-kW 2/1 dual-stator BDFIG (DS-BDFIG) prototype. [ABSTRACT FROM AUTHOR]

Objective To determine cement distribution patterns on therapeutic efficacy after percutaneous vertebroplasty treatment of osteoporotic vertebral compression fractures (OVCFs) with intravertebral cleft (IVC). Methods Patients who were treated with percutaneous vertebroplasty for single OVCFs with IVC and met this study's inclusion criteria were retrospectively reviewed. The follow-up period was at least 2 years. Distribution patterns of cement in the IVC area were respectively specified into 2 groups: group 1: solid lump distribution pattern (n = 22); group 2: the comparatively diffused pattern (n = 90). Radiologic and clinical parameters were analyzed and compared. Then, associations of recollapse with covariates and a risk score were further analyzed and developed to predict recollapse of the augmented vertebrae. Results At the immediate postoperative period, all patients benefited from significant improvement in vertebrae height and kyphotic angle correction. However, significant recollapse was observed at the 2 years postoperative follow-up for the patients in group 1. Furthermore, we found that preoperative severe kyphotic deformity (a cutoff value of 12.5°), solid lump cement distribution pattern, and larger reduction angle (a cutoff value of 8.3°) was significantly associated with increased risk for recollapse. A risk score was developed based on the number of risk factors present in each patient and the receiver operating characteristic curve of the risk score generated an area under the curve of 0.788 (95% confidence interval 0.702–0.873, P = 0.000). Conclusions The comparatively diffused pattern shows better long-term radiologic and clinical outcomes for the treatment for OVCFs with IVC. A risk score can be used to predict the incidence of recollapse. [ABSTRACT FROM AUTHOR]

Tfcp2l1 is a transcription factor critical for mouse embryonic stem cell (mESC) maintenance. However, its role in human ESCs (hESCs) remains unclear. Here, we investigated the role of Tfcp2l1 in controlling hESC activity and showed that Tfcp2l1 is functionally important in the maintenance of hESC identity. Tfcp2l1 expression is highly enriched in hESCs and dramatically decreases upon differentiation. Forced expression of Tfcp2l1 promoted hESC self-renewal. Functional analysis of the mutant forms of Tfcp2l1 revealed that both the CP2- and SAM-like domains are indispensable for Tfcp2l1 to maintain the undifferentiated state of hESCs. Notably, the CP2-like domain is closely related to the suppression of definitive endoderm and mesoderm commitment. Accordingly, knockdown of Tfcp2l1 significantly induced differentiation preferentially into definitive endoderm and mesoderm. Further studies found that inhibition of Wnt/β-catenin signaling pathway by IWR1 is able to eliminate the differentiation caused by Tfcp2l1 downregulation. Taken together, these findings reveal the unique and crucial role of Tfcp2l1 in the determination of hESC fate and will expand our understanding of the self-renewal and differentiation circuitry in hESCs. [ABSTRACT FROM AUTHOR]

Supercapacitors with high energy density and long serving life is highly desirable for solving the energy crisis. Herein, we propose a simple strategy to fabricate hollow cobalt metal-organic framework dodecahedron heterostructures composed of Co(CO 3) 0.5 OH·0.11H 2 O [Co-CH], NiCo 2 S 4 and Co 9 S 8 with controllable energy storage kinetics. The decoration of NiCo 2 S 4 nanosheets provides a 6.1-fold higher specific capacity (1011.0 C g−1 at 1 A g−1) than Co 9 S 8. The electrochemical kinetic analysis reveals that the OH- dissociation process plays a decisive role in the structural stability. Surface-loaded pseudo-capacitive materials can promote the reversibility of Faraday redox reaction and OH- diffusion coefficient. Controlled growth of Co-CH nano-needles reduces the diffusion-dominated process and improve the cycling stability by a factor of 4.0–5.8 due to the increased reaction reversibility, charge transfer and OH- diffusion. The two-electrode asymmetric device displays a high energy density of 47.6 W h kg−1 at a power density of 800 W kg−1 and good cycling stability (78.1 % retention after 5000 cycles at 5 A g−1). This work offers an effective approach for fabricating low-cost transition metal complexes that hold great promise for practical energy storage applications. • Hierarchical Co-MOF hollow complexes composed of Co-CH, NiCo 2 S 4 and Co 9 S 8 are designed. • The decoration of NiCo 2 S 4 nanosheets delivers high specific capacity of 1011.0 C g−1. • The OH- dissociation process is found to be more detrimental to the electrode stability. • Growth of Co-CH nano-needles boosts the cycle stability by 5.8 times. • The ASC delivers an energy density of 47.6 Wh/kg at power density of 800 W kg−1. [ABSTRACT FROM AUTHOR]

The Mesozoic to Cenozoic mountain uplift, exhumation, and deformation of the SW Tianshan Mountains (Kyrgyzstan and Northwest China) offer an important window to understand the intra-continental rejuvenation mechanism of the Central Asian Orogenic Belt (CAOB), as response to the far-field effects of the India-Asia collision. This article presents new observation and data for the planation surface and sedimentation and deformation features of the regional intermountain basins to rebuild the orogenic history in Mesozoic to Cenozoic. Three planation surfaces were recognized by field observation, showing that the mountain may have experienced lengthy erosion since the end Cretaceous, and a continuous planation surface may have formed at the Eocene to Oligocene. The filling sequences and deformation character revealed that the orogenic disintegrate and intermountain basin formation likely began in the end of Oligocene. Subsequently, the uniform planation surface in Western Tianshan may have begun to disintegrate, leading to the basin-and-range landform formation. Folds and nappes in the Cenozoic basins, large-scale thrusting of Palaeozoic rocks over Cenozoic sediments at the basin margin associated with the rapid mountain uplift may have occurred at the end of Early Pleistocene, suggesting a tectonic inversion. The Mesozoic-Cenozoic Tianshan uplift and deformation were likely induced by the collision/accretion along the southern margin of Eurasia. Both the northward propagation of the Parmir syntaxis to the SW Tianshan and the oblique dextral faulting of the Talas-Fergana fault have likely played an important role on the formation and deformation of the Cenozoic basins in the SW Tianshan. [ABSTRACT FROM AUTHOR]

The Natural Resistance Associated Macrophage Protein (Nramp) members play diverse roles in metal transport in plants. Recent studies have showed that OsNrat1 ( OsNramp4 ) encodes an Al transporter, which is required for rice Al tolerance. In this study, we functionally characterized a Nramp member in sorghum, SbNrat1 , which is homologous to OsNrat1 with 88% identity. SbNrat1 was expressed in both roots and shoots, and its expression was not induced by Al treatment. When expressed in yeast, SbNrat1 transports trivalent Al ion, but not Mn and Cd. Furthermore, introduction of SbNrat1 into the rice mutant osnrat1 can rescue its sensitivity to Al. However, no correlation between Al tolerance and the expression level of SbNrat1 was found in thirteen sorghum cultivars tested. These results indicate that SbNrat1 functions as an Al transporter that is possibly involved in basic Al tolerance in sorghum. [ABSTRACT FROM AUTHOR]

Objective: To investigate the age-related growth variation in prostatic parameters by transrectal ultrasound with a simultaneous evaluation of the transitional zone measurements in different prostate volumes.Methods: A retrospective study of 2001 subjects derived from the outpatient clinic at our institution (Shanghai Jiao Tong University Affiliated Sixth People's Hospital in Shanghai) who were diagnosed with benign prostatic hyperplasia (BPH) and prostatitis was reviewed. All subjects were evaluated by the International Prostatic Symptom Score and transrectal ultrasound of the prostate. Statistical analysis was conducted between prostatic parameters and age.Results: The prostate volume, index, length, and width of transitional zone were the parameters most closely associated with increasing age. Notably, the transitional zone measurements showed a significant difference among individuals greater than 50 years old. Moreover, the fastest increasing rate of prostatic parameters was found to be between the ages of 50 and 69. Additionally, we also discovered that the difference between transitional zone parameters and different prostate volumes varies along with increasing age.Conclusion: These results suggest that transitional zone growth is the main contributor to total prostate growth, especially at the ages of 50-69, which may elucidate the higher incidence of the lower urinary tract symptoms from BPH. In view of the increasing rate of transitional zone and the level of total prostate volume, further research is needed to identify the underlying mechanism for such differences in prostate growth. [ABSTRACT FROM AUTHOR]

Previously, our laboratory identified ECE-1, encoding endothelin-converting enzyme-1 (ECE-1), as a positional candidate for a pleiotropic quantitative trait locus affecting femoral size, shape, and biomechanical performance. We hypothesized that endothelin-1 (ET-1) signaling promotes osteogenesis. Exposure of immortalized mouse osteoblast (TMOb) cells to big ET-1 increased mineralization. Following big ET-1 treatment, we measured the secretion of insulin-like-growth factor-1 (IGF1), dickkopf-homolog-1 protein 1 (DKK1), and sclerostin (SOST). In each case, big ET-1 signaling changed secretion in a manner that favored increased osteogenic activity. Treatment with ECE-1, endothelin receptor A (EDNRA), or WNT receptor antagonists inhibited the big ET-1-mediated increase in mineralization. In the presence of big ET-1, message levels of Runx2, Igf1, Dkk1, and Sost are uncoupled from protein production, suggesting posttranscriptional regulation. To evaluate the role of big ET-1 in normal bone physiology, we inhibited EDNRA signaling during mineralization in the absence of exogenous ET-1. EDNRA blockade reduced mineralization, decreased IGF1, and increased DKK1 and SOST secretion, responses opposite to those induced by exogenous big ET-1. Pharmacological and siRNA knockdown to inhibit ECE-1 reduced mineralization and IGF1 secretion with decreasing DKK1 and decreasing or stable SOST secretion, suggesting a further, unknown role of ECE-1 in osteoblast maturation. Previously we identified miR 126-3p as a potential ET-1-responsive regulator of SOST in murine cells. Overexpression of miR126-3p increased mineralization in TMOb cells and decreased SOST secretion. Osteoblasts express the ET-1 signaling pathway and ET-1 signaling is necessary for normal osteoblast differentiation and mineralization, acting through regulation of miRs that target osteogenic molecules. [ABSTRACT FROM AUTHOR]

We previously demonstrated that the survival time of BALB/c mice challenged with Toxoplasma gondii RH strain was prolonged by immunising the mice with a eukaryotic vector expressing the protein ROP16 of T. gondii . Building upon previous findings, we are exploring improved vaccination strategies to enhance protection. In this work, a novel recombinant canine adenovirus type 2 expressing ROP16 (CAV-2-ROP16) of T. gondii was constructed and identified to express ROP16 in Madin-Darby canine kidney cells (MDCK) cells by western blot (WB) and indirect immunofluorescence (IFA) assays. Intramuscular immunisation of BALB/c mice with CAV-2-ROP16 was performed to evaluate the humoral and cellular immune responses. This vaccination triggered significant humoral and cellular responses, including ROP16-stimulated lymphoproliferation ( P < 0.05). Compared to control groups, the CAV-2-ROP16 immunised mice had high production of IFN-γ, IL-2 and IL-12 ( P < 0.05), with a predominance of IgG2a production, but not IL-10 ( P > 0.05), revealing that a predominant Th1-type response had developed. The cell-mediated cytotoxic activity with high levels of IFN-γ and TNF-α was significantly increased in both CD4 + and CD8 + T-cell compartments in the mice immunised with CAV-2-ROP16 ( P < 0.05), compared to three control groups. In addition, when immunised mice were challenged with the RH strain of T. gondii , they showed a significantly increased survival rate (25%) 80 days post infection compared with control mice that all died within seven days ( P < 0.05). The 25% protection rate elicited by the recombinant virus CAV-2-ROP16 has not been achieved in the field of anti- T. gondii vaccination until now. Our work presents the successful use of recombinant virus CAV-2-ROP16 in vaccination protocols to protect against intraperitoneal challenge with the virulent RH strain of T. gondii . This system was shown to be extremely efficient in eliciting humoral and cellular immune responses that led to a significant improvement in survival time in mice. [ABSTRACT FROM AUTHOR]

A new type of structure for opto-electronic oscillator (OEO) is proposed and verified by experiments in this paper. Probing-signal control method for the long-term stability of opto-electronic oscillator (OEO) is proposed firstly and this new method is used to enhance long-term stability of OEO. Using this new method, a low-frequency signal is used as a reference source, getting through the microwave photonic link in OEO and extracting the time-delay fluctuation information and compensated ultimately. In addition, the long-fiber based OEO is injection-locked by a microwave source for suppressing side modes. Results show that the side mode suppression ratio characteristics are improved obviously after microwave source injection and the long-term stability is greatly enhanced by this probing-frequency method and the Allen Deviation of oscillation signal is reduced to 2.7 × 10 −12 during 1 s. [ABSTRACT FROM AUTHOR]

Analysis of the plastic deformation zone at crack tip in fatigue stage II of AA2524-T4 and AA2297-T87 alloys reveals the complex microstructural effects, such as second-phase particles, grain boundaries, Schmid factor and grain orientations, on the formation of slip bands. In AA2524-T4 alloy, slip band formation in plastic deformation zone relies mainly on grain orientation and boundary component. Goss, P and Q grains with low Schmid factor are hard to deform plastically, leading to few slip bands. Cube, S, R, Copper and Brass grains with high Schmid factor tend to form evident slip bands. However, if these grains have pure or high tilt angle component boundaries with adjacent grains, no clear slip bands can be observed because the high FCP rate across these grains fails to allow enough reversible dislocation slipping. Besides, in AA2297-T87 alloy, slip band formation depends heavily on the second-phase particles. From theoretical calculation and quantitative measurement prospective, the large size and density of unshearable T 1 phases can retard dislocation shearing and motion, thereby suppressing the formation of slip bands. [ABSTRACT FROM AUTHOR]

Radiotherapy is widely used in breast cancer treatment. The radiotherapy for breast invasive carcinoma (BRCA) presents challenges with the complex clinical factors, and too many genes have been found to be associated with BRCA radiotherapy prognosis. The aim of this study was to construct an integrative model to combine the clinical data and RNA expression data (including microRNA and mRNA) to predict the survival durations of BRCA patients with radiotherapy. Also, the authors try to find the key regulation pairs between mRNA and miRNA from prediction. They collected mRNA and microRNA expression profiles and gathered the corresponding clinical data of 73 BRCA patients with radiotherapy from The Cancer Genome Atlas (TCGA). According to an integrative model from univariate Cox regression between RNA expression and patient survival, they classified the patients with radiotherapy into low-risk and high-risk groups. The results showed that nine mRNAs were considered as protective genes and five miRNAs and eight mRNAs were considered as high-risk genes. Moreover, the high-risk group has a significantly shorter survival time in comparison with the low-risk group by the log-rank test (p = 0.0039). The reliability of the gene signature was validated by an independent data set from the Gene Expression Omnibus (GEO). Furthermore, three pairs of miRNA-mRNA, closely associated to survival, were identified. These findings and method may prove valuable for improving the clinical management of BRCA patients with radiotherapy. [ABSTRACT FROM AUTHOR]

This paper dedicates on the rotor dynamics behaviour research on the turbo-expander rotor system involving droplet impact. A stochastic model based on Beta distribution and Bernoulli distribution of droplet generation is established and the formulations of droplet impact forces are deduced, which is applied on the rotor dynamics equations of the tilting pad bearing supported turbo-expander considering the temperature gradient for a further analysis. A time domain research is carried out and a conclusion that continuously droplet impact will perturb the steady vibration of the turbo-expander rotor system is obtained. Monte Carlo method is implemented for a statistics dynamics research and the results suggests that in the design of expander impellers, in order to decrease the uncertainty brought by droplet impact, the number of channels should be as few as possible, the droplet impact should be controlled to occur uniformly, and the collision, entrainment of the primary droplets and the stripping of the liquid film on the blade should be strictly restrained. [ABSTRACT FROM AUTHOR]

[Display omitted] • The Dengying Formation and the early Cambrian dolostone units are high-quality reservoirs for MVT ores in the Upper Yangtze. • Both depositional facies and post-depositional modification govern the reservoir development for MVT Zn-Pb ores. • The reservoir horizons mainly located in the tidal flat facies and subordinately in the platform margin mound-shoal facies. • Sabkha environment of dolostone horizons with brecciation and dolomitization/silicification are important prospecting targets. Reservoirs as the direct targets for hydrocarbon exploration represent the permeable and porous rocks. In this sense, reservoirs provide the crucial control for Mississippi Valley-type (MVT) Zn-Pb ore formation, but they have received less attentions in the research field of MVT deposits. Based on reprocessing published data and the field and petrographic observations, this study reviews the characteristics and genesis of the reservoirs for MVT ores in the Dengying Formation and the early Cambrian dolostone units around the Proterozoic/Cambrian boundary in the Upper Yangtze block. The reservoir horizons consist of breccias and coarse-grained carbonates at the top of a shallowing-upward sedimentary cycle mainly in the tidal flat facies and subordinately in the platform margin mound-shoal facies. Bird's eye and zebra textures are common in the reservoir horizons and the pseudomorphs after evaporite minerals can be found in the breccias. Moreover, the breccia bodies have a large lateral extension up to kilometers level, sharp boundaries with the enclosing rocks, and are absent of carbonate dissolution-related internal sediments, where the clasts are angular and show a downward collapse from their primitive stratigraphic positions. These suggest that the reservoir dolostones deposited in a sabkha environment and the breccias mainly resulted from evaporite dissolution. Multistage dolomitization and silicification intensively superimposed on the reservoir horizons and might take advantage of pre-existing interclast, intergranular, and dissolution pores. The related intercrystalline pores provide the predominant spaces for the Zn and Pb sulfide precipitation. Pressure dissolution- and structural deformation-related factures provide minor reservoir spaces. Prospecting MVT Zn-Pb ores in the Proterozoic/Cambrian boundary dolostone units in the Upper Yangtze block should give priority to the sabkha environment of dolostone horizons with post-depositional brecciation and dolomitization/silicification at the top of a shallowing-upward sedimentary cycle in the tidal flat facies and in the platform margin mound-shoal facies. [ABSTRACT FROM AUTHOR]

To obtain high energy density supercapacitors (SCs) to meet the larger demand for electric vehicles and portable electronic products, increasing the mass loading of electrode materials without sacrificing electron and ion conductivity is an ideal avenue. Herein, stable α-phase NiCoAl hydroxides with an expanded interlayer spacing and superior electronic conductivity are efficiently synthesized via the coprecipitation method. Furthermore, the interface is ingeniously regulated by adjusting the proper concentration of the electrolyte to modulate the charge storage form of the electrode to resolve the structure collapse and block ion penetration/diffusion. As expected, the obtained NiCoAl-10 supercapacitor electrode under an ultrahigh mass loading (20.24 mg cm−2) has an ultrahigh area-specific capacitance of 23.85 F cm−2 at 10 mA cm−2, an excellent rate capability of 19.27 F cm−2, even at 40 mA cm−2, and an outstanding long-term cycling stability (87.5% capacity retention after 10,000 cycles). Ultimately, an asymmetric supercapacitor (ASC) device of NiCoAl-10//active carbon (AC) also exhibits a high energy density of 3.29 mWh cm−2 at 18.00 mW cm−2 and remarkable capacity retention. This work further interprets the energy storage mechanism of NiCoAl hydroxides under high mass-loading, and opens a new avenue for meeting the commercial application of high energy density SCs. [Display omitted] • Al-substituted NiCo layered double hydroxides electrodes are constructed. • The Ni 0.75 Co 0.15 Al 0.1 (OH) 2 electrode possesses an ultrahigh mass loading. • The Ni 0.75 Co 0.15 Al 0.1 (OH) 2 electrode exhibits outstanding performances. • This work opens a new avenue for meeting the commercial application of SCs. [ABSTRACT FROM AUTHOR]

• An N-doped graphite layer was first as a coating layer of SnO 2. • Graphene coating can provide conductive network and alleviate volume expansion. • Nitrogen doping can provide active centers and improve interface stability. • SnO 2 @NG displays the outstanding electrochemical performances. Tin dioxide (SnO 2) with multiple electron transport is considered as a potential substitute for graphite due to these advantages of natural abundance, environmental friendliness, and high theoretical capacity. However, the ineluctable volume change and structural crushing limit its practical application. Hence, SnO 2 is coated by an N-doped graphite layer to form the flexible composite anode (SnO 2 @NG), which can provide a conductive network, increase the electronic conductivity, and effectively mitigate the irreversible volume expansion/contraction during the circulation process. Furthermore, the SnO 2 @NG anode shows a high specific capacity and stable cycle performance in lithium-ion batteries (677.7 mAh g−1 after 100 cycles) and sodium-ion batteries (169.7 mAh g−1 after 100 cycles). This excellent electrochemical performance illustrates that SnO 2 @NG has broad application prospects for high-performance energy storage systems. [ABSTRACT FROM AUTHOR]

Biomechanics plays a critical role in the modulation of chondrocyte function. The mechanisms by which mechanical loading is transduced into intracellular signals that regulate chondrocyte gene expression remain largely unknown. Histone deacetylase 4 (HDAC4) is specifically expressed in chondrocytes. Mice lacking HDAC4 display chondrocyte hypertrophy, ectopic and premature ossification, and die early during the perinatal period. HDAC4 has a remarkable ability to translocate between the cell's cytoplasm and nucleus. It has been established that subcellular relocation of HDAC4 plays a critical role in chondrocyte differentiation and proliferation. However, it remains unclear whether subcellular relocation of HDAC4 in chondrocytes can be induced by mechanical loading. In this study, we first report that compressive loading induces HDAC4 relocation from the cytoplasm to the nucleus of chondrocytes via stimulation of Ser/Thr-phosphoprotein phosphatases 2A (PP2A) activity, which results in dephosphorylation of HDAC4. Dephosphorylated HDAC4 relocates to the nucleus to achieve transcriptional repression of Runx2 and regulates chondrocyte gene expression in response to compression. Our results elucidate the mechanism by which mechanical compression regulates chondrocyte gene expression through HDAC4 relocation from the cell's cytoplasm to the nucleus via PP2A-dependent HDAC4 dephosphorylation. [ABSTRACT FROM AUTHOR]

Objectives: This paper aims to investigate whether equibiaxial tensile strain alters chondrocyte gene expression via controlling subcellular localization of histone deacetylase 4 (HDAC4). Materials and Methods: Murine chondrocytes transfected with GFP-HDAC4 were subjected to 3 h cyclic equibiaxial tensile strain (CTS, 6% strain at 0.25 Hz) by a Flexcell® FX-5000™ Tension System. Fluorescence microscope and western blot were used to observe subcellular location of HDAC4. The gene expression was analyzed by real-time RT-PCR. The concentration of Glycosaminoglycans in culture medium was quantified by bimethylmethylene blue dye; Collagen II protein was evaluated by western blot. Cells phenotype was identified by immunohistochemistry. Cell viability was evaluated by live-dead cell detect kit. Okadaic acid, an inhibitor of HDAC4 nuclear relocation, was used to further validate whether HDAC4 nuclear relocation plays a role in gene expression in response to tension stimulation. Results: 87.5% of HDAC4 was located in the cytoplasm in chondrocytes under no loading condition, but it was relocated to the nucleus after CTS. RT-PCR analysis showed that levels of mRNA for aggrecan, collagen II, LK1 and SOX9 were all increased in chondrocytes subjected to CTS as compared to no loading control chondrocytes; in contrast, the levels of type X collagen, MMP-13, IHH and Runx2 gene expression were decreased in the chondrocytes subjected to CTS as compared to control chondrocytes. Meanwhile, CTS contributed to elevation of glycosaminoglycans and collagen II protein, but did not change collagen I production. When Okadaic acid blocked HDAC4 relocation from the cytoplasm to nucleus, the changes of the chondrocytes induced by CTS were abrogated. There was no chondrocyte dead detected in this study in response to CTS. Conclusions: CTS is able to induce HDAC4 relocation from cytoplasm to nucleus. Thus, CTS alters chondrocytes gene expression in association with the relocation of HDAC4 induced by CTS. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the relationship between five previously established serum osteoarthritis biomarkers and the severity of cartilage lesions in the knee. Cartilage damage (classified according to the Outerbridge scoring system) and serum concentrations of cartilage oligomeric matrix protein (COMP), collagen type II C-telopeptide (CTX-II), matrix metalloproteinase-3 (MMP-3), collagen type III N-propeptide, (PIIINP), and hyaluronic acid (HA) were determined in 79 patients who underwent knee arthroscopy or total knee replacement. HA and COMP concentrations were significantly higher in the Outerbridge score 1 and 2 groups, respectively. These results suggest that serum COMP and HA concentrations can be used to predict early cartilage lesions in the knee. [ABSTRACT FROM PUBLISHER]

Purpose: The aim of this prospective multi-institutional phase 2 study was to investigate disease control, survival outcomes, and toxicity after thoracic three-dimensional radiation therapy (3D-RT) with concurrent chemotherapy for newly diagnosed stage IV non-small cell lung cancer (NSCLC). Methods and Materials: Eligible patients were 18 to 80 years of age, had a Karnofsky performance status (KPS) score ≥70%, and newly diagnosed stage IV NSCLC with limited metastatic disease (defined as involving ≤3 organs). Patients received platinum-doublet chemotherapy with concurrent irradiation to the primary tumor. Primary endpoints were overall survival (OS) and acute toxicity. Results: From May 2008 to May 2012, 198 eligible patients were enrolled from 7 cancer centers. Most patients died with distant metastasis; only 10% died with isolated primary recurrence. Median OS time was 13.0 months (95% confidence interval [CI]: 11.7-14.3); OS rates were 53.5% at 1 year, 15.8% at 2 years, and 9.2% at 3 years. Median progression-free survival (PFS) time was 9.0 months (95% CI: 7.7-10.3); corresponding PFS rates were 30.8%, 8.2%, and 6.1%. The 1-year, 2-year, and 3-year local (primary tumor) control rates were 78.8%, 57.7%, and 55.4%. Multivariate analysis showed that delivery of ≥63 Gy to the primary tumor (P=.014), having a primary tumor volume <134 cm(3) (P=.008), and having a stable or higher KPS score after treatment (P=.01) were independent predictors of better OS. The most common severe (grades 3-4) acute toxicities were hematologic: leukopenia (37.9%), thrombocytopenia (10.1%), and anemia (6.9%). No patients experienced grade 4 or 5 radiation-related toxicity; 2.5% had acute grade 3 pneumonitis, and 6.6% had acute grade 3 radiation esophagitis. Conclusions: Thoracic 3D-RT to the primary tumor with concurrent chemotherapy led to satisfactory survival outcomes with acceptable toxicity. Radiation dose, primary tumor volume, and PFS after treatment all predicted survival in these patients with limited-metastasis NSCLC. [ABSTRACT FROM AUTHOR]

Carbon ion therapy (CIT) is a form of particle therapy, which not only spares normal tissues but may also improve local control of recurrent intracranial tumours. Cerebral radiation necrosis (RN) is one of the most serious adverse reactions of recurrent brain tumours following reirradiation, which may lead to neurological decline or even death. Bevacizumab is an anti-vascular endothelial growth factor antibody, which has been used to treat symptomatic RN. However, studies on bevacizumab for the treatment of CIT-induced RN are sparse. The present study described two cases that were successfully treated with bevacizumab for symptomatic RN following CIT for recurrent intracranial malignant tumours. The two recurrent intracranial malignant tumours, a chondrosarcoma in the right cavernous sinus and an anaplastic meningioma in the right frontal lobe, were enrolled in a clinical trial of CIT. Both cases were treated intravenously with bevacizumab when deterioration that appeared to be symptomatic brain RN was observed. Just before CIT, enhanced magnetic resonance imaging (MRI) was performed in each case to confirm tumour recurrence. Both cases exhibited a deterioration in symptoms, as well as on MRI, at 12-month intervals following CIT. The first case underwent positron emission tomography/computed tomography to confirm no increase in fluorodeoxyglucose uptake in lesion areas. Both cases were diagnosed as having symptomatic brain RN and began intravenous administration of four cycles of 5 mg/kg bevacizumab biweekly. The patients responded well, with rapid and marked improvements on MRI, and in clinical symptoms. No tumour progression was observed 24 months after CIT. In conclusion, bevacizumab was revealed to exert marked effects on symptomatic brain RN following CIT. Notably, cycles of bevacizumab should be administered specifically based on the aim of treating brain necrosis, and long-term or prophylactic applications are not recommended. [ABSTRACT FROM AUTHOR]

Brassinosteroids (BRs) are important hormones that regulate plant development and physiology. Substantial progresses have been made in BR-related studies, and especially an increasing number of new genes involved in BR biosynthesis have been identified. Here, we characterize a BR-related rice mutant, small grain 4 ( sg4), obtained from callus culture of japonica cultivar Nipponbare. This mutant showed multiple phenotypes such as dark green, rugose erect leaves and small round grains. It was higher than the wild type, different from the majority of BR- and gibberellin-related mutants. Genetic analysis showed that the mutant phenotypes are controlled by a single recessive locus. The gene was fine-mapped to a 90.7-kb interval with 1,100 F recessive individuals by means of map-based cloning. Totally 11 open reading frames were found in this interval, only one of which was detected with an 8-bp insertion in the 5′UTR region by sequencing. Functional complementation test revealed that a DWARF11 allele, LOC_Os04g39430, is answer for the mutant phenotype of sg4. Tissue-specific response to BR and decreased expression levels of BR biosynthetic genes suggest that sg4 is a weak BR-deficient mutant. These results are beneficial to understanding the physiological action of sg4 in a more comprehensive way. [ABSTRACT FROM AUTHOR]