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: In view of the unclear understanding of the basic scientific problems such as the rheological mechanism of seed cotton, especially the lack of research on the creep characteristics of seed cotton, the machine-harvested seed cotton in the Xinjiang region was taken as the research object to find out the compression creep characteristics. The universal material testing machine was used to carry out a one-factor creep test, taking moisture content, feed quality, compression times, and trash content as test factors and instantaneous elastic modulus, hysteretic elastic modulus, viscosity coefficient, and delay time as test indicators. The ANOVA and correlation were analyzed by SPSS, and the creep process of the seed cotton was simulated by ADAMS. Results show that moisture content significantly affects the instantaneous elastic modulus, hysteretic elastic modulus, and viscosity coefficient (p<0.01). In addition, each value of which decreases with the increase in moisture content. Feed quality significantly affects the hysteretic elastic modulus and viscosity coefficient (p<0.05). Moreover, the hysteretic elastic modulus and viscosity coefficient increase with the increase in feed quality. The compression times significantly influence the instantaneous elastic modulus, hysteretic elastic modulus, and viscosity coefficient (p<0.01), each value of which increases with the increase of compression times. Furthermore, the trash content significantly influenced the hysteretic elastic modulus and viscosity coefficient (p<0.05). The absolute error between the simulated and experimental values ek is within -0.011-0.030 mm, and the relative error φk is less than 7%. The experimental results can provide theoretical and data support for the study of rheological characteristics of machine-harvested seed cotton, the design of seed cotton packing devices, and the molding quality of cotton bale (mold). [ABSTRACT FROM AUTHOR]

Sn-based high-temperature Pb-free (HTLF) solder pastes have been developed as a drop-in solution to replace high- Pb solder pastes in power discrete applications. The pastes were designed with Indium Corporation's DurafuseVR technology, to combine the merits of two constituent powders. A SnSb-based Ag/ Cu-containing high-temperature powder, with a melting temperature above 320°C, was designed to maintain high-temperature performance. A Sn-rich SnAgCu-Sb powder, with a melting temperature around 228°C, was added to the paste to enhance wetting and improve joint ductility. In the design, the final joint will have the low-melting phase (the melting temperature >228°C) in a controllable quantity embedded into the high-melting SnSb matrix. HTLF-1, one of the designs, maintained the bond shear strength up to 15 MPa, even around 290°C. Another design, HTLF-2, has a similar bond shear strength as Pb92.5/Sn5/Ag2.5 around 290°C, but exceeds substantially below 250°C. The power discrete components had been built with both HTLF solder pastes for both die-attach and clip-bond through the traditional high-Pb process, which demonstrated the drop-in processing compatibility. The components survived three additional surface mounting (SMT) reflows (peak temperature upto 260°C) and passed moisture sensitivity level 1 (MSL1). This confirmed that the maintained joint strength (comparable to or stronger than high-Pb), helped to keep the joint integrity within the encapsulated components in the following SMT process, even with the controlled quantity of the melting phases above 228°C. Both HTLF solder pastes outperformed Pb92.5/Sn5/Ag2.5 in the resistance from drain to source when power is on (RDS(on)), even after 1,000 cycles of temperature cycling test (TCT) under 255/175°C, which is attributed to the intrinsic lower electrical resistivity of Sn in both HTLF pastes. Microstructural observation had shown no corner cracks for both die-attach and clip-bond joints after TCT. [ABSTRACT FROM AUTHOR]

Aim: The TTC21B gene is now known as causative of nephronophthisisrelated ciliopathies (NPHP-RC).We reported two Chinese paediatric cases with end-stage renal disease and other phenotypes caused by the TTC21B gene mutations. Methods: The clinical features of Chinese paediatric cases with NPHP-RC were summarized. Mutation analysis of the TTC21B gene was performed using nextgeneration sequencing. Results: The twocases both had nephrotic proteinuria, renal failure, hypertension and abnormal liver function (or hepatic fibrosis). One case also presented situs inversus and short phalanges. They developed end-stage renal disease (ESRD) at 1 year old and 8 years old, respectively, when renal pathology both showed focal segmental glomerular sclerosis (FSGS) with tubulointerstitial lesions including interstitial fibrosis and atrophic tubules. Three novel diseasecausing TTC21B mutations were identified. One case carried homozygous mutation c.2211 +3A>G,while the other case carried compoundheterozygous mutations c.1552 T > C (p.C518R) and c.1456dupA (p.R486KfsX22). Conclusion: Mutations in TTC21B cause a range of ciliopathy phenotypes in humans. We identified 3 novel TTC21B mutations in two Chinese paediatric cases that both presented end-stage renal disease and other different features. This is the first TTC21B mutations ever reported in China. [ABSTRACT FROM AUTHOR]

Controllable and flexible fabrication of ultrathin and uniform oxide layer-wrapped noble metal nanoparticles (NPs) has been expected. Here a new strategy is presented for them based on colloidal electrostatic attraction and self-assembly on the metal NPs via one-step laser ablation of noble metal targets in the hydrolysis-induced hydroxide sol solutions at room temperature. The Au NPs, with several tens of nanometers in size, are taken as core part and TiO2 as shell-layer to demonstrate the validity of the presented strategy. It has been shown that the TiO2 shell-wrapped Au NPs are obtained after laser ablation of Au target in the hydrolysis-induced Ti(OH)4 sol solution. The Au NPs are about 35 nm in mean size, and the TiO2 shell layers are amorphous in structure and about 2.5 nm in thickness. The shell thickness is nearly independent of the Au NPs' size. Further experiments have shown that the thickness and crystallinity of the shell-layer can be tuned and controlled via changing the temperature or pH value of the Ti(OH)4 sol solution or prolonging the laser ablation duration. The formation of the TiO2 shell-wrapped Au NPs is attributed to attachment and self-assembly of Ti(OH)4 colloids on the laser-induced Au NPs due to the electrostatic attraction between them. Importantly, the presented strategy is universal and suitable for fabrication of many other ultrathin oxide-wrapped noble metal NPs. A series of oxide shell-wrapped noble metal NPs have been successfully fabricated, such as Au@oxides (Fe2O3, Al2O3, CuO, and ZnO) as well as Pt@TiO2 and Pd@TiO2, etc. Further, compared with the pure gold NPs-built film, the TiO2-wrapped Au NPs-built film has exhibited much stronger surface enhanced Raman scattering (SERS) performance to the anions NO3-, which weakly interact with noble metals, and the good reusability for the SERS-based detection of 4-nitrophenol, which could be photodegraded by xenon lamp irradiation. This work provides a flexible and universal route to the ultrathin and uniform oxide layer-wrapped noble metal NPs. [ABSTRACT FROM AUTHOR]

A very simple route is developed for fast fabrication of nanosized amorphous titanium dioxide (TiO2) hollow spheres (THPs) just via dropping the pure four titanium chloride (TiCl4) liquid droplets into deionized water at around room temperature. The THPs, at around 80 nm in mean diameter, can be formed within a few seconds after dropping TiCl4 droplets into water. The shell layers of the obtained THPs are amorphous and porous in structure with a porosity of 58-80% and show a linear increase in thickness with the size of THPs. Further experiments have revealed that the reaction temperature, initial pH value, and size of the TiCl4 droplet are crucial to the formation, size, productivity, and microstructure of the THPs. A model is proposed on the basis of the fragmentation of liquid droplets, hydrolysis-induced formation, and inward growth of TiO2 shell layers, which can well describe the formation of the THPs. Importantly, such amorphous nanoscaled THPs have exhibited some strong hollow structure-enhanced performances. Typically, the THP-built film shows the highest reflectivity in the visible region compared to the other structured TiO2 films. Especially, if it supports the film of the Au nanoparticle, the surface-enhanced Raman scattering effect is significantly enhanced by more than 1 order of magnitude. This work provides not only a simple and quick fabrication method for the THPs but also a new member for their family. [ABSTRACT FROM AUTHOR]

A facile and chemically clean method is presented to fabricate the nanostructured tungsten oxide (WO3) based on laser ablation of a tungsten flake in water and a subsequent hydrothermal route. The typically nanostructured WO3 objects were well-dispersed and brick-like in shape. The bricks have average dimensions of ca. 200 nm in length, 150 nm in width and 130 nm in thickness, with stepped structures on their planar surfaces. Further experiments revealed that the reaction temperature, pH value and composition of the precursor in the subsequent hydrothermal treatment are crucial to formation of the brick-like WO3 nanostructures. Correspondingly, a rectangular cuboidal stacking growth model is proposed to describe the formation of such nanobricks. The nanobricks could be good building blocks of complex micro/nanostructures and devices. Also, the combination of laser ablation in liquid with hydrothermal treatment could provide an effective synthetic approach for morphologically tunable WO3 nanomaterials, which have potential applications in gas sensing, electrochromic devices and photocatalysis. [ABSTRACT FROM AUTHOR]

Alport syndrome (AS) is a progressive renal disease characterized by haematuria and progressive renal failure. An accurate genetic diagnosis of AS is very important for genetic counselling and even prenatal diagnosis. We detected mutation of COL4An by amplifying the entire coding sequence mRNA of peripheral blood lymphocytes using polymerase chain reaction (PCR) in five Chinese AS families who asked for genetic counselling and prenatal diagnosis, then performed prenatal genetic diagnosis for four families. Mutation analysis of the foetus was made using DNA extracted from amniocytes. Foetus sex was determined by PCR amplification of SRY as well as karyotype analysis. Maternal cell contamination was excluded by linkage analysis. Four different COL4A5 gene variants and two COL4A3 gene variants were detected in the five families. Because there was a de novo mutation in family 2, prenatal diagnosis was performed for the other four families. Results showed a normal male foetus for family 1 and family 4, respectively. Results showed an affected male foetus for families 3 and 5, and the pregnancies were terminated. An easier, faster and efficacious method for COL4An gene mutation screening based on mRNA analysis from peripheral blood lymphocytes was established. Prenatal genetic diagnosis was performed in four AS families in China. Prenatal genetic diagnosis was performed in Alport syndrome families in China. A rapid and efficacious method for screening of the COL4An gene mutation for Alport syndrome is presented, based on mRNA analysis from peripheral blood lymphocytes. [ABSTRACT FROM AUTHOR]

Alport syndrome (AS) is a progressive renal disease characterized by hematuria and progressive renal failure. X-linked dominant AS (XLAS) is the major inheritance form, accounting for almost 80 of the cases, caused by mutations in COL4A5gene. An accurate genetic diagnosis of AS is very important for genetic counseling and even prenatal diagnosis. In this study we detected mutation of COL4A5by amplifying the entire coding sequence mRNA of peripheral blood lymphocytes using nested PCR in a Chinese XLAS family, and then performed the first prenatal diagnosis of AS in China. Mutation analysis of the fetus was performed on both cDNA-based level and DNA-based level of amniocytes. Fetus sex was determined by PCR amplification of SRYand karyotypes analysis. Maternal cell contamination was excluded by linkage analysis. There was a G-to-A substitution at position 4271 in exon 46 of COL4A5gene (c.G4271A) in the pregnant woman; this genetic variant has not been described previously and was a novel missense mutation. The fetus did not carry the same mutation as the mother. PCR amplification product of SRYand karyotypes analysis revealed a male fetus. Linkage analysis showed that there was no contamination of maternal cells in amniocytes. [ABSTRACT FROM AUTHOR]

Land use and land cover changes (LUCC) are thought to be amongst the most important impacts exerted by humans on climate. However, relatively little research has been carried out so far on the effects of LUCC on extreme climate change other than on regional temperatures and precipitation. In this paper, we apply a regional weather research and forecasting (WRF) climate model using LUCC data from Heilongjiang Province, that was collected between the 1900s and 2010s, to explore how changes in forest cover influence extreme temperature indexes. Our selection of extreme high, low, and daily temperature indexes for analysis in this study enables the calculation of a five-year numerical integration trail with changing forest space. Results indicate that the total forested area of Heilongjiang Province decreased by 28% between the 1900s and 2010s. This decrease is most marked in the western, southwestern, and northeastern parts of the province. Our results also reveal a remarkable correlation between change in forested area and extreme high and low temperature indexes. Further analysis enabled us to determine that the key factor explaining increases in extreme high temperature indexes (i.e., calculated using the number of warm days, warm nights, as well as tropical nights, and summer days) is decreasing forest area; data also showed that this factor caused a decrease in extreme low temperature indexes (i.e., calculated using the number of cold days and cold nights, as well as frost days, and ice days) and an increase in the maximum value of daily minimum temperature. Spatial data demonstrated that there is a significant correlation between forest-to-farmland conversion and extreme temperature indexes throughout most of our study period. Spatial data demonstrated that there is a significant correlation between forest-to-farmland conversion and extreme temperature indexes throughout most of our study period. Positive correlations are also present between decreasing forest area, the more frequent occurrence of extreme high temperature events, and a rise in the maximum value of daily minimum temperature. At the same time, we found clear negative correlations between decreasing forest area and less frequent occurrence of extreme low temperature events. [ABSTRACT FROM AUTHOR]

Amodified seed growth routewas developed to fabricate theAu nanocrystalswith high-density tips based on kinetically-controlled growth via adjusting the adding rate of Au seeds into growth solution. The obtained Au nanostructures were chestnut-like in morphology and about 100 nm in size. They were built of the radial [111]-oriented nanoneedles andwere 30-50 nmin length. Therewere about 120-150 tips in each nanocrystal. The formation of chestnut-like Au nanocrystals is ascribed to surfactant-induced preferential growth of seeds along direction [111]. Importantly, the chestnut-like Au configuration displayed powerful surface enhanced Raman scattering (SERS) performance (enhance factor > 107), owing to the high density of tips. Further, such film was used as a SERS substrate for the detection of lindane (γ -666) molecules (the typical organochlorine pesticide). The detection limit was about 10 ppb, and the relationship between SERS intensity I and concentration C of 666 accords with the double logarithm linear. This work presents a simple approach to Au nanocrystal with high-density tips, and provides a highly efficacious SERS-substrate for quantitative and trace recognition of toxic chlorinated pesticides. [ABSTRACT FROM AUTHOR]

Male infertility accounts for almost half of infertility cases worldwide. A subset of infertile men exhibit reduced testosterone and enhanced levels of estradiol (E2), though it is unclear how increased E2 promotes deterioration of male fertility. Here, we utilized a transgenic mouse strain that overexpresses human CYP19, which encodes aromatase (AROM+ mice), and mice with knockout of Esr1, encoding estrogen receptor α (ERαKO mice), to analyze interactions between viable Leydig cells (LCs) and testicular macrophages that may lead to male infertility. In AROM+ males, enhanced E2 promoted LC hyperplasia and macrophage activation via ERα signaling. E2 stimulated LCs to produce growth arrest--specific 6 (GAS6), which mediates phagocytosis of apoptotic cells by bridging cells with surface exposed phosphatidylserine (PS) to macrophage receptors, including the tyrosine kinases TYRO3, AXL, and MER. Overproduction of E2 increased apoptosis-independent extrusion of PS on LCs, which in turn promoted engulfment by E2/ERα-activated macrophages that was mediated by AXL-GAS6-PS interaction. We further confirmed E2-dependant engulfment of LCs by real-time 3D imaging. Furthermore, evaluation of molecular markers in the testes of patients with nonobstructive azoospermia (NOA) revealed enhanced expression of CYP19, GAS6, and AXL, which suggests that the AROM+ mouse model reflects human infertility. Together, these results suggest that GAS6 has a potential as a clinical biomarker and therapeutic target for male infertility. [ABSTRACT FROM AUTHOR]

The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) was reported to be participated in tumor development. The association between hnRNP A1 and liver cancer and the functional role of hnRNP A1 in liver cancer have never been reported. Herein, hnRNP A1-specific single-stranded DNA aptamer, BC15, was used to (a) evaluate hnRNP A1 expression in liver cancer, and (b) treat hepatocarcinoma by acting as an inhibitor of hnRNP A1. Results showed that there is high hnRNP A1 expression in liver cancer including serum a-feto- protein--negative liver cancer tissues compared with either para-cancer or benign controls. Down regulation of hnRNP A1 expression by RNA interference inhibits the proliferation and migration of cancerous HepG2 cells, while overexpression of hnRNP A1 in normal HL-7702 cells increased the proliferation and migration of the cells. Importantly, BC15 showed a stronger inhibiting effect on the proliferation of cultured hepatoma cells than hnRNP A1 small interfering RNA, strongly suggesting that BC15 could also be a potential drug candidate for an hnRNP A1 inhibitor besides its prospect utility in in situ histological examination. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to investigate the safety and pharmacokinetics of edaravone administered by single or successive intravenous infusions in healthy Chinese volunteers. Methods: A total of 30 subjects (15 males and 15 females) were recruited and randomly assigned to three groups receiving edaravone doses of 20, 30, and 60 mg. All subjects received a single dose of edaravone during a 30-minute period, and only the 30mg dose group continued to receive the same dose successively by intravenous infusion twice daily for the next 5 days. Plasma concentrations of edaravone were monitored by high-performance liquid chromatography at the following times: 15, 30, 45, 60, 75, 105, 165, 225, 300, 390, 480, 600, and 720 minutes after edaravone administration. Results: The area under the plasma concentration-time curve during a dosage interval (AUCτ) values of the single dose in the 20, 30, and 60 mg dose groups were 3.64 ± 1.37, 5.17 ± 0.93, and 11.25 ± 3.42 mg · h/L, respectively, while in the group receiving repeated dosing of 30mg, the mean AUCτ value was 5.06 ± 0.89mg · h/L. The corresponding maximum plasma drug concentration (Cmax) values were 1599.0 ± 382.6, 2378.7 ± 316.7, and 4540.1 ± 901.1 ng/mL, respectively, in the single-dose groups, and 2479.1 ± 477.9 ng/mL in the 30mg repeated-dose group. The mean AUCτ and Cmax ratios between the repeated-dose group and the single-dose groups were 0.98 and 1.04. All laboratory test abnormalities (including increased alanine transaminase and triacylglycerol levels, and decreased white blood cell counts and creatinine levels) were mild and tolerable. All abnormal blood biochemical indices returned to normal levels after 7 days. Conclusion: Edaravone was safe and well tolerated in the volunteers and displayed linear increases in the Cmax and AUCτ values. [ABSTRACT FROM AUTHOR]

Background: Bencycloquidium bromide (BCQB) is a novel, potent and selective muscarinic M1/M3 receptor antagonist under development for the treatment of rhinorrhea in rhinitis. The pharmacokinetics and safety of BCQB in animals have been established in preclinical studies. However, no clinical pharmacokinetic data are available for BCQB in humans. Objective: The aim of this first-in-human study was to evaluate the pharmacokinetics, safety and tolerability of BCQB following single and multiple intranasal doses in healthy Chinese subjects. Methods: The clinical trial was comprised of the following four studies: (i) an open-label, single-dose escalation study to evaluate the safety and tolerability in healthy subjects after intranasal doses of BCQB ranging from 45 to 450 μg (total of six doses); (ii) an open-label, multiple-dose escalation study to assess the safety and tolerability in healthy subjects after intranasal administration with 120 and 150 μg doses of BCQB (360 and 450 μg/day) administered three times daily for 15 days; (iii) a randomized, open-label and parallel-group design to evaluate the single-dose pharmacokinetics of BCQB after intranasal dosing (45, 90, and 180 μg); and (iv) ten subjects received 120 μg of BCQB by intranasal administration, three times daily for 5 days with a final single dose on day 7 to assess its multiple-dose pharmacokinetics. Safety and tolerability of BCQB were evaluated by monitoring adverse events (AEs), ECG recordings, vital signs and clinical laboratory parameters. The pharmacokinetic parameters for BCQB were calculated by software using noncompartmental methods. Results: All AEs were mild, of limited duration and no more frequent at higher doses. There was no serious adverse event, death or withdrawal. No clinically significant change was noted in clinical laboratory parameters, cardiac parameters or vital signs. Following single intranasal dosing, BCQB was rapidly absorbed with a median time to maximum concentration (tmax) of 8 minutes for 45, 90, and 180 μg dose groups; the plasma concentration of BCQB decreased in a biphasic manner with the mean half-life (t½) of 8.5 hours; the maximum concentration (Cmax) and area under the plasma concentration-time curve (AUC) of BCQB increased linearly across the examined dose range of 45-180 μg. During the multiple dosing, the steady state was achieved within 3 days of 120 mg three times daily dosing of BCQB. A slightly greater AUC was observed after 5 days of multiple dosing, with the mean accumulation ratio of 1.26; however, the half-life was unchanged. Conclusion: BCQB was safe and well tolerated in healthy Chinese subjects when administered intranasally with single and multiple doses across the doses studied. The mean Cmax and AUC increased proportionally to the studied doses, and the steady state was achieved within 3 days after three times daily dosing. A slight accumulation of BCQB following multiple dosing was observed. The pharmacokinetics, safety and tolerability profiles of BCQB pose it as a good candidate for further development in the treatment of rhinorrhea in rhinitis. [ABSTRACT FROM AUTHOR]

We report on a Chinese girl with Frasier syndrome (FS). She presented with steroid-resistant focal segmental glomerulosclerosis (FSGS) and male pseudohermaphroditism. The WT1 IVS 9 + 5 G>A mutation was detected in one allele in the proband. The ratio of +KTS/−KTS was 0.67 in the proband’s cDNA. The expression of podocyte molecules (WT1, nephrin, podocin, α-actinin 4 and CD2AP) were also investigated in a renal specimen of this FS patient. WT1 expression showed diffuse nuclear staining, with less obvious speckles in the patient’s glomeruli than in those of controls. The distribution and intensity of podocyte molecules were altered both in normal- and abnormal-appearing glomeruli. In conclusion, the study presented a case of FS by clinical manifestation, renal pathology, karyotype analysis and genetic testing. A lower ratio of +KTS/−KTS and an abnormal distribution of WT1, as well as abnormal expressions of other podocyte molecules, were also revealed. The mechanisms of WT1 mutation causing FS still need to be investigated. [ABSTRACT FROM AUTHOR]

Rapid, ultrasensitive and reliable detection of mercury ions (Hg2+) by surface enhanced Raman spectroscopy (SERS) is of importance, but is restricted by the extremely low Raman cross section of the Hg2+. Here, we report a facile methodology that can realize such detection based on the organometallic Cu(CH4N2S)Cl · 0.5H2O nanobelts and SERS. In the assay, Hg2+ react with the nanobelts coated on a SERS active gold nanoparticle (NP) film to form ultrafine HgS NPs in situ. Subsequently, solid HgS is SERS determined to mirror the presence of Hg2+. Importantly, such detection is rapid and ultrasensitive. Within 10 min, limit of detection (LoD) of ppt level can be realized. The high detection efficiency is attributed to the superhydrophilicity, rich micropores and ultrathin nature of the organometallic nanobelts besides the strong SERS effect of Au NP film. In addition, this detection is highly resistant to various metal ions (Cu2+, Fe3+, Bi3+, Cr3+, Na+, Ni2+, Cd2+, etc) and is highly reliable in actual water (lake and tap water). Finally, influences of some substrate parameters and detection conditions on the test results are revealed. The optimal thickness of the gold NP film is about 80 nm, and the optimal wavelength of excitation light is about 633 nm. A small amount of Cu(CH4N2S)Cl · 0.5H2O nanobelts or a large volume of Hg2+ contaminated solution contributes to low LoDs. We believe that this work provides a rapid and sensitive detection for Hg2+. [ABSTRACT FROM AUTHOR]