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Plant roots are sustained through meristem activity at the root tip. Two transcriptional pathways, one mediated by PLETHORAs (PLTs) and the other by SHORTROOT and SCARECROW, play major roles in root meristem development. The role of PLTs during root meristem development requires a concentration gradient, which is not only contributed by posttranslational regulation such as growth dilution and intercellular movement but also likely by a largely unknown fine-tuned transcriptional regulatory mechanism. We report here that Arabidopsis (Arabidopsis thaliana) JANUS positively regulates PLT1 expression in the root meristem by recruiting RNA polymerase II (Pol II) to PLT1 and by interacting with PLT1. JANUS-dependent recruitment of Pol II is inhibited through the competitive binding of JANUS by GRF-INTERACTING FACTOR1 (GIF1)/ANGUSTIFOLIA3, a transcriptional cofactor that negatively regulates PLT1 expression. Finally, GIF1 and JANUS, the antagonistic regulators of PLT1, both depend on Arabidopsis IMPORTIN β4 for their nuclear accumulation. The combination of an importin and its two antagonistic cargos in PLT1 transcription may have logistic benefits in fine-tuning the transcription of PLT1 in root meristem.

Male and female gametophytes are generated from micro- or megaspore mother cells through consecutive meiotic and mitotic cell divisions. Defects in these divisions often result in gametophytic lethality. Gametophytic lethality was also reported when genes encoding ribosome-related proteins were mutated. Although numerous ribosomal proteins (RPs) have been identified in plants based on homology with their yeast and metazoan counterparts, how RPs are regulated, e.g., through dynamic subcellular targeting, is unknown. We report here that an Arabidopsis (Arabidopsis thaliana) importin β, KETCH1 (karyopherin enabling the transport of the cytoplasmic HYL1), is critical for gametogenesis. Karyopherins are molecular chaperones mediating nucleocytoplasmic protein transport. However, the role of KETCH1 during gametogenesis is independent of HYPONASTIC LEAVES 1 (HYL1), a previously reported KETCH1 cargo. Instead, KETCH1 interacts with several RPs and is critical for the nuclear accumulation of RPL27a, whose mutations caused similar gametophytic defects. We further showed that knocking down KETCH1 caused reduced ribosome biogenesis and translational capacity, which may trigger the arrest of mitotic cell cycle progression and lead to gametophytic lethality.

Ovule development is critical for seed development and plant reproduction. Multiple transcription factors (TFs) have been reported to mediate ovule development. However, it is not clear which intracellular components regulate these TFs during ovule development. After their synthesis, TFs are transported into the nucleus a process regulated by karyopherins commonly known as importin alpha and β. Around half of Arabidopsis (Arabidopsis thaliana) importin β-coding genes have been functionally characterized but only two with specific cargos have been identified. We report here that Arabidopsis IMPORTIN β4 (IMB4) regulates ovule development through nucleocytoplasmic transport of transcriptional coactivator growth regulating factors–interacting factors (GIFs). Mutations in IMB4 impaired ovule development by affecting integument growth. imb4 mutants were also defective in embryo sac development, leading to partial female sterility. IMB4 directly interacts with GIFs and is critical for the nucleocytoplasmic transport of GIF1. Finally, functional loss of GIFs resulted in ovule defects similar to those in imb4 mutants, whereas enhanced expression of GIF1 partially restored the fertility of imb4. The results presented here uncover a novel genetic pathway regulating ovule development and reveal the upstream regulator of GIFs.

To investigate the correlation of the single nucleotide polymorphisms rs995030 and rs4474514 of the tyrosine kinase receptor-specific ligand (KITLG) gene with the risk of male infertility.This study included 360 patients with idiopathic male infertility and 338 healthy fathers as controls, all from the surrounding areas of Nanjing. According to the 5th edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen, we divided the infertility patients into an azoospermia (n = 143), a severe oligozoospermia (n = 159), and an oligozoospermia group (n = 58). We obtained the basic clinical data on all the subjects, collected genomic DNA from the peripheral blood of the patients, determined the genotypes of the KITLG gene rs995030 and rs4474514 by sequence mass-array, and analyzed the correlation between the two-point gene polymorphism and male infertility by logistic regression analysis.Statistically significant differences were observed between the infertility patients and normal fertile controls in sperm concentration (［13.23 ± 24.52］ vs ［78.74 ± 61.25］ ×10⁶/ml, P0.01), the percentage of progressively mobile sperm (［18.71 ± 15.19］% vs ［39.36 ± 9.75］%, P0.01), and the level of FSH (［16.09 ± 17.31］ vs ［4.56 ± 2.41］ IU/L, P0.01), but not between the genotypes and male infertility, and no correlation was found in subgroup analysis.The single nucleotide polymorphisms rs995030 and rs4474514 of the KITLG gene were not significantly correlated with male infertility, which is to be further verified by more studies with samples of larger size and expanded selection range.

Pollen development is a pre-requisite for sexual reproduction of angiosperms, during which various cellular activities are involved. Pollen development accompanies dynamic remodeling of vacuoles through fission and fusion, disruption of which often compromises pollen viability. We previously reported that the Y subunit of adaptor protein 1 (AP1G) mediates synergid degeneration during pollen tube reception. Here, we demonstrate that AP1G is essential for pollen development. AP1G loss-of-function resulted in male gametophytic lethality due to defective pollen development. By ultrastructural analysis and fluorescence labeling, we demonstrate that AP1G loss-of-function compromised dynamic vacuolar remodeling during pollen development and impaired vacuolar acidification of pollen. Results presented here support a key role of vacuoles in gametophytic pollen development.

Plant roots are sustained through meristem activity at the root tip. Two transcriptional pathways, one mediated by PLETHORAs (PLTs) and the other by SHORTROOT and SCARECROW, play major roles in root meristem development. The role of PLTs during root meristem development requires a concentration gradient, which is not only contributed by posttranslational regulation such as growth dilution and intercellular movement but also likely by a largely unknown fine-tuned transcriptional regulatory mechanism. We report here that Arabidopsis (Arabidopsis thaliana) JANUS positively regulates PLT1 expression in the root meristem by recruiting RNA polymerase II (Pol II) to PLT1 and by interacting with PLT1. JANUS-dependent recruitment of Pol II is inhibited through the competitive binding of JANUS by GRF-INTERACTING FACTOR1 (GIF1)/ANGUSTIFOLIA3, a transcriptional cofactor that negatively regulates PLT1 expression. Finally, GIF1 and JANUS, the antagonistic regulators of PLT1, both depend on Arabidopsis IMPORTIN β4 for their nuclear accumulation. The combination of an importin and its two antagonistic cargos in PLT1 transcription may have logistic benefits in fine-tuning the transcription of PLT1 in root meristem.

Concurrent hearing and genetic screening of newborns is expected to play important roles not only in early detection and diagnosis of congenital deafness, which triggers intervention, but also in predicting late-onset and progressive hearing loss and identifying individuals who are at risk of drug-induced HL. Concurrent hearing and genetic screening in the whole newborn population in Beijing was launched in January 2012. This study included 180,469 infants born in Beijing between April 2013 and March 2014, with last follow-up on February 24, 2018. Hearing screening was performed using transiently evoked otoacoustic emission (TEOAE) and automated auditory brainstem response (AABR). For genetic testing, dried blood spots were collected and nine variants in four genes, GJB2, SLC26A4, mtDNA 12S rRNA, and GJB3, were screened using a DNA microarray platform. Of the 180,469 infants, 1,915 (1.061%) were referred bilaterally or unilaterally for hearing screening; 8,136 (4.508%) were positive for genetic screening (heterozygote, homozygote, or compound heterozygote and mtDNA homoplasmy or heteroplasmy), among whom 7,896 (4.375%) passed hearing screening. Forty (0.022%) infants carried two variants in GJB2 or SLC26A4 (homozygote or compound heterozygote) and 10 of those infants passed newborn hearing screening. In total, 409 (0.227%) infants carried the mtDNA 12S rRNA variant (m.1555A>G or m.1494C>T), and 405 of them passed newborn hearing screening. In this cohort study, 25% of infants with pathogenic combinations of GJB2 or SLC26A4 variants and 99% of infants with an m.1555A>G or m.1494C>T variant passed routine newborn hearing screening, indicating that concurrent screening provides a more comprehensive approach for management of congenital deafness and prevention of ototoxicity.

To investigate the correlation between the single nucleotide polymorphism (SNP) rs662 of the paraoxonase 1 gene (PON1) and the risk of male infertility.This case-control study included 403 male idiopathic infertility patients aged 29.00 ± 4.48 years in the case group and 329 normal fertile men aged 28.28 ± 4.08 years as healthy controls. We obtained DNA from the peripheral venous blood of the subjects, genotyped the SNP rs662 of PON1 by Sequenom MassArray, and analyzed the association between different genotypes of PON1 rs662 and male infertility using the logistic regression model.Compared with the normal controls, the infertility patients showed a significantly increased level of follicle-stimulating hormone (FSH) (［16.30 ± 17.76］ vs ［4.72 ± 2.51］ U/L, P0.01) but a decreased percentage of progressively motile sperm (PMS) (［7.40 ± 14.17］ % vs ［41.93 ± 9.06］ %, P0.01) and sperm concentration (［2.74 ± 3.64］ vs ［75.83 ± 63.66］ ×10⁶/ml, P0.01). Statistically significant differences were not found in the other parameters between the two groups of subjects, nor in the correlation of male infertility with the heterozygous genotype GA versus the wild homozygous genotype GG (OR = 0.98, 95% CI: 0.63－1.53, P = 0.923) or the homozygous genotype AA versus the wild homozygous genotype GG (OR = 0.87, 95% CI: 0.56－1.34, P = 0.525).The SNP rs662 of PON1 was not correlated with male infertility, which, however, needs to be confirmed by further studies with larger samples from a larger area.目的： 探讨对氧磷酶1（PON1）基因rs662(c.575AG)位点单核苷酸多态性与男性不育发病风险之间的相关性。方法： 采用病例-对照研究的方法，选取403例特发性男性不育患者作为病例组，329例正常生育的男性作为对照组。病例组年龄为(29.00 ± 4.48)岁，对照组年龄为(28.28± 4.08)岁。取外周静脉血，并用DNA试剂盒提取DNA，随后用Sequenom MassArray技术对PON1 rs662位点进行基因分型，分析PON1 rs662位点不同基因型与男性不育发病风险之间的相关性。 结果： 病例组与对照组相比，卵泡刺激素［ (16.30±17.76) U/L vs (4.72±2.51) U/L］、前向运动精子百分率［(7.40±14.17) % vs (41.93±9.06) %］、精子浓度［ (2.74±3.64) ×10⁶/ml vs (75.83±63.66) ×10⁶/ml］ 存在明显差异且具有统计学意义（P0.01），其他参数无统计学意义的差异。杂合突变型GA与野生型纯合GG相比较：OR=0.98，95%CI：0.63~1.53，P=0.923，纯合突变型AA与野生型纯合GG相比较：OR=0.87，95%CI：0.56~1.34，P=0.525。两组结果均显示PON1 rs662位点与男性不育发病风险之间无相关性，各亚组分析显示该基因多态性位点与男性不育发病风险之间不存在相关性。结论： PON1 rs662位点基因多态性与男性不育发病风险之间不存在相关性，但是由于实验样本条件的限制，需要更大的样本量以及样本选取范围进行进一步研究。

Double fertilization in angiosperms requires the delivery of immotile sperm through pollen tubes, which enter embryo sacs to initiate synergid degeneration and to discharge. This fascinating process, called pollen tube reception, involves extensive communications between pollen tubes and synergids, within which few intracellular regulators involved have been revealed. Here, we report that vacuolar acidification in synergids mediated by AP1G and V-ATPases might be critical for pollen tube reception. Functional loss of AP1G or VHA-A, encoding the γ subunit of adaptor protein 1 or the shared component of two endomembrane V-ATPases, respectively, impaired synergid-controlled pollen tube reception and caused partial female sterility. AP1G works in parallel to the plasma membrane-associated receptor FERONIA in synergids, suggesting that synergid-mediated pollen tube reception requires proper sorting of vacuolar cargos by AP1G. Although AP1G did not mediate the targeting of V-ATPases, AP1G loss of function or the expression of AP1G-RNAi compromised vacuolar acidification mediated by V-ATPases, implying their genetic interaction. We propose that vacuolar acidification might represent a distinct cell-death mechanism specifically adopted by the plant phylum, which is critical for synergid degeneration during pollen tube reception.

In PWM controlled variable rate spraying system, spraying quantities were regulated by fast switching solenoid valves. However, hydraulic impacts were generated by these fast switching solenoid valves in pipe system, which affected stabilities of spraying quantities and atomization characteristics. In order to study pressure changing regularities when solenoid valves operated, then to design a pressure controller to improve spraying qualities in PWM controlled variable rate spraying system, Fluent was used to simulate pressure characteristics in the pipe system and pressure curves were drawn under the following 3 working conditions, solenoid valve opening, closing, and switching continuously with 5 Hz frequency and 50% duty ratio. Related experiments were carried out to test real pressure signals in the pipe based on a PWM controlled variable rate spraying system. Relative errors between simulation results and experiment results were below 10%. Thus, this simulation model of PWM controlled variable rate spraying system in Fluent was reliable to simulate pressure characteristics in the pipe in other common working conditions, and which contributed to design pressure controller and to optimize the whole PWM controlled variable rate spraying system.

Grid-stiffened cylindrical shells are widely applied in aviation and aerospace engineering. Bearing capacities of grid-stiffened cylindrical shells will be reduced by local heating. In this study, numerical simulation method is applied to deduce the temperature distribution of the grid-stiffened cylindrical shells subjected to high power laser irradiation. Temperature dependent aluminum alloy properties are fully considered in the process of numerical simulation. Comparing to smooth thin-wall cylindrical shells, the effect of ribs size to temperature distribution is studied. As the material properties varying with temperature, the temperature rising rate is higher at the initial period when cylindrical shell is subjected to laser irradiation. The temperature rising rate gradually reduces with irradiation time increasing. Buckling analysis was performed to obtain the buckling bearing capacity and the effect of local heating on grid-stiffened cylindrical shells subjected to local heating.

With the rapid development of city, many large and medium-sized cities sprawl in urban space,triggering a series of socio-economic issues related to land-use. Based on RS and GIS, selected Kunming as study area for its typical representation of Yunnan plateau mountain cities, used the method of spatial quadrant orientation analysis, obtained the number and structure of construction land expansion in specific direction of study area in period of two different years, and calculated the intensity index and fractal dimensions of the urban expansion. Finally, according to local conditions, spatial expansion variations features of Kunming were analyzed systematically.

Planar morphogenesis, a distinct feature of multicellular organisms, is crucial for the development of ovule, progenitor of seeds. Both receptor-like kinases (RLKs) such as STRUBBELIG (SUB) and auxin gradient mediated by PIN-FORMED1 (PIN1) play instructive roles in this process. Fine-tuned intercellular communications between different cell layers during ovule development demands dynamic membrane distribution of these cell-surface proteins, presumably through vesicle-mediated sorting. However, the way it’s achieved and the trafficking routes involved are obscure. We report that HAPLESS13 (HAP13)-mediated trafficking of SUB is critical for ovule development. HAP13 encodes the μ subunit of adaptor protein 1 (AP1) that mediates protein sorting at the trans-Golgi network/early endosome (TGN/EE). The HAP13 mutant, hap13-1, is defective in outer integument growth, resulting in exposed nucellus accompanied with impaired pollen tube guidance and reception. SUB is mis-targeted in hap13-1. However, unlike that of PIN2, the distribution of PIN1 is independent of HAP13. Genetic interference of exocytic trafficking at the TGN/EE by specifically downregulating HAP13 phenocopied the defects of hap13-1 in SUB targeting and ovule development, supporting a key role of sporophytically expressed SUB in instructing female gametogenesis., Author Summary Ovules, being the progenitors of seeds, hold an important role in crop production. Ovule is a complex organ connecting two generations, i.e. diploid sporophytic cells and haploid female gametophytes (FG). Fertilization of female gametes leads to the development of embryo and endosperm while the sporophytic cells of ovules become seed coats. Because of its importance for plant reproduction, the development of ovules is tightly controlled. The integument cells are divided in a polar way so that integument cell layers fully enclose a mature FG, leaving an opening only for pollen tube entrance. The integuments also instruct FG development, synchronizing the two generations. Receptor-like kinases, especially STRUBBELIG (SUB), are crucial both for the establishment of ovular polarity and the intercellular communication between sporophytic and gametophytic cells. However, how SUB is post-translationally regulated, as would be expected for cell-surface proteins, is unclear. We report here that the dynamic trafficking of SUB via a subpopulation of endosomes is crucial for its functionality during ovule development. The membrane association of SUB was impaired when the recycling route from the trans-Golgi network/early endosome to the plasma membrane was disrupted in hap13-1, a mutant of HAPLESS13. We further demonstrate that defects of SUB targeting in the outer integuments compromised FG development, suggesting an intriguing intercellular communication. Our results highlight the importance of vesicular trafficking in the establishment of ovular polarity and in the communications between spatially separated cells.

A direct transition metal-free regioselective C-3 amidation of electron-deficient indoles is developed with commercially available N-fluorobenzenesulfonimide (NFSI) as the nitrogen source.

To investigate the effect of Vibrant Soundbridge (VSB) implantation.In accordance with the indications for VSB implantation, surgeries were done for two patients who suffered from either a sensorineural or conductive hearing loss (microtia). Their preoperative auditory thresholds (0.5, 1, 2 and 4 kHz) were 56 dB HL and 61 dB HL. The VSB was turned on and adjusted seven weeks after surgery.Postoperative auditory thresholds of the two patients were improved. Their pure tone thresholds were 32 dB HL and 40 dB HL, and the respective improvement was 24 dB HL and 21 dB HL. There was no facial paralysis, vertigo and tinnitus.Patients with a sensorineural or conductive hearing loss may benefit from VSB implantation.

Material requirement planning (MRP) is a popular approach used in production processes for planning. Many forms of uncertainty in practice affect the production process and different approaches have been presented for MRP with uncertainty. In order to model MRP problem under fuzzy uncertainty, we present a fuzzy programming model with recourse based on credibility theory. We consider fuzzyvariables coefficients related to the market demand and theunit price of material on spot market. The objective value is minimizing the expected value of total material procurement cost. This proposed MRP problem belongs to an infinitedimensional optimization problem that cannot be solved directly and it is 0-1 mix integer program, neither linear nor convex, traditional optimization algorithms cannot be used to solve it. So to solve the presented MRP model, we design a hybrid algorithm which combines approximation approach (AA) and particle swarm optimization (PSO). We also present one numerical example to illustrate the effectiveness of the designed algorithm.

To explore the electrophysiological results and rehabilitation outcome of two prelingually deafened pediatric cochlear implant patients with auditory neuropathy.Preoperative audiological evaluation, intra-postoperative electrically evoked auditory brainstem response (EABR) and neural response telemetry (NRT) record for the two cases were conducted in Beijing Tongren Hospital. A one year follow-up was performed. Data collected before and at 6,12-month intervals after implantation were compared with that from control pediatric cochlear implant patients matched for the same duration of implant use as this two cases.The two children implanted had not had any postoperative medical or cochlear implant device complications. Intraoperative EABR and NRT were elicited in case 1 with unrepeatable waveforms. After 12 months of training, Case 1 had shown significant improvements in sound detection, speech perception abilities and communication skills, which was better than the control group, and the electrophysiological results became normal. Case 2 had also benefited from cochlear implantation, even though no recognizable NRT was found until he returned 12 month after the operation. CONTUSIONS: The desynchronization of auditory path had been changed after the electrical stimulation ongoing 12 months for children with auditory neuropathy. The two children had not had any complications postoperatively, and each child had shown improved listening and communication skills. Cochlear implantation could help patients with auditory neuropathy to improve their communication skill and go back to the main stream.

Accurate short-term traffic flow forecasting is one of the important issues for intelligent transportation systems research, especially for the advanced traffic management systems and advanced traveler information systems research. With the shortening of the forecasting term, the uncertainty of traffic flow becomes more and more seriously, so that the forecasting effect of general approaches is decreasing. For an example, the algorithm based on non-parametric regression is a real-time nonparametric forecasting algorithm with the characteristic of high transplantation and accuracy, which plays an important role in traffic flow forecasting, yet there is the problem of "dimension curse" as the dimensions of the sample data increase. For the purpose of solving the question of short-time traffic flow forecasting, a short-time traffic flow forecasting model based on projection pursuit auto-regression technique is established in this paper. The problem of "dimension curse" and non-normality among high-dimensions data are solved. This algorithm satisfies the need of real-time traffic flow forecasting completely through the field data test

Chronic prostatitis is a common andrologic disease. The etiology and pathogensis of the disease are not yet completely understood. This article reviews the origin and the molecular strucure of cytokines and their role in the pathogenesis of prostatitis, especially chronic nonbacterial prostatitis/chronic pelvic pain syndrome.

To evaluate the change of peripheral Th1/Th2 cells in patients with CAP/CPPS and its significance in various clinical types of CAP/CPPS.Interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) secreted by CD3+ CD8(-)T cells were detected by flow cytometry in 35 patients with CAP/CPPS and 12 healthy volunteers, and significance of Th1/Th2 cells ratio in the etiology of CAP/CPPS was analyzed.Compared with control group, peripheral Th1 cells were significantly increased in patients with IIIA and III B CAP/CPPS, the Th1/Th2 cell ratio was apparently increased (P0.05), while Th2 cells was not different from that in the control(P0.05 ); Th1, Th2 cells and Th1/Th2 in patients with IIIA CPPS were not statistically different from those in III B CPPS respectively (P0.05) .There is a Th1/Th2 imbalance in CAP/CPPS patients with an increase of Th1 type cytokines. Th1 cell may play an important role in the pathogenesis of CAP/CPPS.