Circuit-specific gene therapy is knocking on the door of Parkinson's disease

Parkinson's disease(PD)is a prevalent neurodegenerative disorder that affects millions of individuals worldwide.Symptoms of PD typically manifest as movement impairments,including bradykinesia,rigidity,tremors,and postural instability,as well as non-motor symptoms,such as cognitive decline,pain,and depression(Bloem et al.,2021).

Active and stable Cu doped NiMgAlO catalysts for upgrading ethanol to n-butanol

Upgrading ethanol to n-butanol is an attractive way for renewable n-butanol production. Herein, Cu was selected to modify NiMgAlO catalysts for improving ethanol conversion and n-butanol selectivity. Over the optimized 2%Cu-NiMgAlO catalyst, ethanol conversion and n-butanol selectivity were enhanced to 30.0% and 64.2%, respectively, in 200 h time on stream at 523 K. According to physicochemical characterizations and theoretical calculations, the key role of multiple active sites in this reaction was extensively investigated. The plate-like structure of hydrotalcite was maintained over 2%Cu-NiMgAlO catalysts, with an average Ni particle size of ca. 5.4 nm. The presence of Cu species created CuNi alloy sites and Lewis acid-base pairs, and increased hydrogen transfer and condensation reactions, resulting in elevated ethanol conversion and n-butanol selectivity. Additionally, CuNi alloy had a strong interaction with CuNiMgAl oxides, forming homogeneous boundary due to their close ionic radius and lattice matching, and afforded the long time stability in the ethanol to n-butanol reaction.

低浓度台盼蓝囊膜染色技术在白内障手术中的应用

目的:探讨台盼蓝染色晶状体前囊膜的最低有效浓度,评价白内障手术中应用囊膜染色技术的临床意义。方法:收集2014-03/2016-12成熟期年龄相关性白内障患者60例60眼,晶状体皮质混浊程度为C4～C5、核混浊程度为N3(以晶状体混浊分类系统Ⅱ为标准),随机分为三组。三组患者术中分别使用0.03%、0.015%和0.0075%三种不同浓度台盼蓝。所有患者均由同一经验丰富手术医生完成手法小切口白内障手术。术中观察前囊膜染色情况以及撕囊难易程度。记录连续环形撕囊术(continuous circular capsulorhexis,CCC)成功、后囊袋破裂以及人工晶状体囊袋内植入情况。观察术后1d,1wk,3mo术眼角膜内皮细胞计数、眼压、前房炎症反应、角膜水肿和眼内结构染色情况。结果:浓度低至0.015%的台盼蓝仍可对晶状体前囊膜有效染色,顺利完成CCC。0.03%与0.015%两组患者CCC成功率和IOL囊袋内植入率均高于0.0075%组,差异均有统计学意义(P<0.0083)。三组患者后囊破裂发生率和角膜内皮细胞平均损失率两两比较,差异均无统计学意义(P>0.0083)。术后晶状体前囊撕囊口边缘及侧切口的着染均于1wk内消失,未见其他眼内结构蓝染,前房炎症反应轻,未发现超过1wk的角膜水肿和眼压升高。结论:白内障手术中应用台盼蓝晶状体前囊膜染色技术安全有效,可提高手术成功率,建议使用台盼蓝最低有效浓度为0.015%。

Delayed improvements in visual memory task performance among chronic schizophrenia patients after high-frequency repetitive transcranial magnetic stimulation

BACKGROUND Cognitive impairments are core characteristics of schizophrenia,but are largely resistant to current treatments.Several recent studies have shown that highfrequency repetitive transcranial magnetic stimulation(rTMS)of the left dorsolateral prefrontal cortex(DLPFC)can reduce negative symptoms and improve certain cognitive deficits in schizophrenia patients.However,results are inconsistent across studies.AIM To examine if high-frequency rTMS of the DLPFC can improve visual memory deficits in patients with schizophrenia.METHODS Forty-seven chronic schizophrenia patients with severe negative symptoms on stable treatment regimens were randomly assigned to receive active rTMS to the DLPFC(n=25)or sham stimulation(n=22)on weekdays for four consecutive weeks.Patients performed the pattern recognition memory(PRM)task from the Cambridge Neuropsychological Test Automated Battery at baseline,at the end of rTMS treatment(week 4),and 4 wk after rTMS treatment(week 8).Clinical symptoms were also measured at these same time points using the Scale for the Assessment of Negative Symptoms(SANS)and the Positive and Negative Syndrome Scale(PANSS).RESULTS There were no significant differences in PRM performance metrics,SANS total score,SANS subscores,PANSS total score,and PANSS subscores between active and sham rTMS groups at the end of the 4-wk treatment period,but PRM performance metrics(percent correct and number correct)and changes in these metrics from baseline were significantly greater in the active rTMS group at week 8 compared to the sham group(all P<0.05).Active rTMS treatment also significantly reduced SANS score at week 8 compared to sham treatment.Moreover,the improvement in visual memory was correlated with the reduction in negative symptoms at week 8.In contrast,there were no between-group differences in PANSS total score and subscale scores at either week 4 or week 8(all P>0.05).CONCLUSION High-frequency transcranial magnetic stimulation improves visual memory and reduces negative symptoms in schizophrenia,but these effects are delayed,potentially due to the requirement for extensive neuroplastic changes within DLPFC networks.

Measurement of Secondary Electron Energy Spectra of Polymethyl Methacrylate

We report on a novel and convenient method of measuring secondary electron spectra for insulators in a secondary electron yield measurement system with a planar grid analyzer configuration and a metal mesh probe. In this measurement, the planar grid is negatively biased to force some emitted secondary electrons to return to the sample surface and to neutralize charges accumulated on the sample during the previous beam irradiation. The surface potential of the sample is then measured by use of a metal mesh probe. The grid bias for neutralization corresponding to the zero surface potential is determined based on the linear relationship between the surface potential and the grid bias. Once the surface potential equals zero, the secondary electron spectra of polymethyl methacrylate（PMMA） are studied experimentally by measuring the -curve and then fitting it to Everhart＇s formula. The measurement results show that the peak energy and the full width at half maximum of the spectra are 4.26 eV and 14.06 eV, respectively.

New Approach for Measured Surface Localization Based on Umbilical Points

Measured surface localization （MSL） is one of the key essentials for the assessment of form error in pre- cision manufacturing. Currently, the researches on MSL have focused on the corresponding relation search between two surfaces, the performance improvement of localization algorithms and the uncertainty analysis of localization. However, low efficiency, limitation of localization algo- rithms and mismatch of multiple similarities of feature points with no prior are the common disadvantages for MSL. In order to match feature points quickly and fulfill MSL efficiently, this paper presents a new localization approach for measured surfaces by extracting the generic umbilics and estimating their single complex variables, describing the match methods of ambiguous relation at umbilics, presenting the initial localization process of one pair matched points, refining MSL on the basis of obtained closet points for some measured points by the improvement directed projection method. In addition, the proposed algorithm is simulated in two different types of surfaces,two different localization types and multiple similar sur- faces, also tested with the part of B-spline surface machined and bottle mould with no knowledge, finally the initial and accurate rigid body transformation matrix, localization errors between two surfaces and execution time are got. The experimental results show that the pro- posed method is feasible, more accurate in localization and high in efficiency. The proposed research can not only improve the accuracy and performance of form error assessment, but also provide an effective guideline for the integration of different types of measured surfaces.

Composition and Development Prospects of Scented Rice

Containing higher aromatic composition,scented rice is better than ordinary rice varieties in taste and nutrition. Major composition of scented rice is 2-acetyl-1-pyrroline( 2-AP). Different scented rice varieties have different content of 2-AP. The content of 2-AP is not only influenced by genetic factors,but also closely connected with types and content of nutrition elements in soil,soil moisture management,environmental temperature,and storage. 2-AP synthesis and regulation are possibly connected with Proline and enzyme.

Study on the thermally induced spindle angular errors of a five-axis CNC machine tool

Thermally induced spindle angular errors of a machine tool are important factors that affect the machining accuracy of parts.It is critical to develop models with good generalization abilities to control these angular thermal errors.However,the current studies mainly focus on the modeling of linear thermal errors,and an angular thermal error model applicable to different working conditions has rarely been investigated.Furthermore,the formation mechanism of the angular thermal error remains to be studied.In this study,an analytical modeling method was proposed by analyzing the formation and propagation chain of the spindle angular thermal errors of a five-axis computer numerical control(CNC)machine tool.The effects of the machine tool structure and position were considered in the modeling process.The angular thermal error equations were obtained by analyzing the spatial thermoelastic deformation states.An analytical model of the spindle angular thermal error was established based on the geometric relation between thermal deformations.The model parameters were identified using the trust region least squares method.The results showed that the proposed analytical model exhibited good generalization ability in predicting spindle pitch angular thermal errors under different working conditions with variable spindle rotational speeds,spindle positions,and environmental temperatures in different seasons.The average mean absolute error(MAE),root mean square error(RMSE)and R2 in twelve different experiments were 4.7μrad,5.6μrad and 0.95,respectively.This study provides an effective method for revealing the formation mechanism and controlling the spindle angular thermal errors of a CNC machine tool.

Evaluation of precipitation extremes over the Tibetan plateau using the NASA global daily downscaled datasets NEX-GDDP-CMIP6

The utility of statistically downscaled data is in its provision of detailed,high-resolution insights,surpassing global models,which is essential for precise assessments of climate impact.This study delves into the changes in extreme precipitation across the Tibetan Plateau(TP)and its five subregions,thereby deepening our understanding of climate impacts in the region.Employing NASA Earth Exchange Global Daily Downscaled Climate Projections(NEX-GDDP-CMIP6),which are bias-corrected and statistically downscaled,in conjunction with three gauge-based datasets(CN05.1,CMFD,GMFD)spanning from 1979 to 2014,this study conducts an extensive analysis using eight extreme precipitation indices in the TP.The findings reveal significant spatial disparities in extreme precipitation,with the southern subregion experiencing a sig-nificant increase while the two northern subregions show statistically insignificant changes.NEX-GDDP-CMIP6 performs best in the eastern subregion but fails to capture extreme precipitation characteristics in the southern and western subregions.Averaging over the whole period of 1979-2014(climatology),the NEX-GDDP-CMIP6 dataset performs better on the intensity and persistence indices than on the absolute and relative threshold indices.NEX-GDDP-CMIP6's performance on climate trends is significantly below that of climatology.The NEX-GDDP-CMIP6 dataset has limitations over the TP because of its reliance on the underperforming GMFD reference data.This study provides a comprehensive understanding of the variability of extreme precipitation and disparities among different subregions of the TP,laying a robust scientific groundwork for climate impact studies and future projection in this region.

Correction to:Efficient derivation of extended pluripotent stem cells from NOD-scid II2rg^-/-mice

Figure 1.Generation of NOD-scid II2rg^-1-extended pluripotent stem cells.(A)Schematic of two approaches used for generating NOD-scid II2rg^-1-extended pluripotent stem cells:de novo derivation from blastocysts(upper panels)and chemical reprogramming from embryonic fibroblasts(lower panels).(B)Phase-contrast images of de novo derived outgrowth and EPS colonies for 17 passages in LCDM medium.Scale bars,100 pm.(C)qRT-PCR analysis of XEN marker genes expression during the chemical induction process(day 16).Error bars indicate SEM(n=2).(D)Co-immunostaining of XEN marker genes during the chemical induction process(day 16).Upper panels:GATA6 and SALL4;lower panels:SOX17 and SALL4.Scale bars,100 pm.

Efficient derivation of extended pluripotent stem cells from NOD-scid II2rg-/-mice

Recently we have established a new culture condition enabling the derivation of extended pluripotent stem(EPS)cells,which,compared to conventional pluripotent stem cells,possess superior developmental potential and germline competence.However,it remains unclear whether this condition permits derivation of EPS cells from mouse strains that are refractory or non-permissive to pluripotent cell establishment.Here,we show that EPS cells can be robustly generated from non-permissive NOD-sc/d Il2rg 1 mice through de novo derivation from blastocysts.Furthermore,these cells can also be efficiently generated by chemical reprogramming from embryonic NOD-sc/d II2rg-/-fibroblasts.NOD-sc/d II2rg-/-EPS cells can be expanded for more than 20 passages with genomic stability and can be genetically modified through gene targeting.Notably,these cells contribute to both embryonic and extraembryonic lineages in vivo.More importantly,they can produce chimeras and integrate into the E13.5 genital ridge.Our study demonstrates the feasibility of generating EPS cells from refractory mouse strains,which could potentially be a general strategy for deriving mouse pluripotent cells.The generation of NOD-sc/d II2rg-/-Yaqin Du and Ting Wang contributed equally to this work.Electronic supplementary material The online version of this article(https://doi.org/10.1007/s13238-018-0558-z)contains supplementary material,which is available to authorized users.EPS cell lines permits sophisticated genetic modification in NOD-scid II2rg-/-mice,which may greatly advance the optimization of humanized mouse models for biomedical applications.