Enhancing Density Maps by Removing the Majority of Particles in Single Particle Cryogenic Electron Microscopy Final Stacks.

Over the past decade, advancements in technology and methodology within the field of cryogenic electron microscopy (cryo-EM) single-particle analysis (SPA) have substantially improved our capacity for high-resolution structural examination of biological macromolecules. This advancement has ushered in a new era of molecular insights, replacing X-ray crystallography as the dominant method and providing answers to longstanding questions in biology. Since cryo-EM does not depend on crystallization, which is a significant limitation of X-ray crystallography, it captures particles of varying quality. Consequently, the selection of particles is crucial, as the quality of the selected particles directly influences the resolution of the reconstructed density map. An innovative iterative approach for particle selection, termed CryoSieve, significantly improves the quality of reconstructed density maps by effectively reducing the number of particles in the final stack. Experimental evidence shows that this method can eliminate the majority of particles in final stacks, resulting in a notable enhancement in the quality of density maps. This article outlines the detailed workflow of this approach and showcases its application on a real-world dataset.

A minority of final stacks yields superior amplitude in single-particle cryo-EM.

Cryogenic electron microscopy (cryo-EM) is widely used to determine near-atomic resolution structures of biological macromolecules. Due to the low signal-to-noise ratio, cryo-EM relies on averaging many images. However, a crucial question in the field of cryo-EM remains unanswered: how close can we get to the minimum number of particles required to reach a specific resolution in practice? The absence of an answer to this question has impeded progress in understanding sample behavior and the performance of sample preparation methods. To address this issue, we develop an iterative particle sorting and/or sieving method called CryoSieve. Extensive experiments demonstrate that CryoSieve outperforms other cryo-EM particle sorting algorithms, revealing that most particles are unnecessary in final stacks. The minority of particles remaining in the final stacks yield superior high-resolution amplitude in reconstructed density maps. For some datasets, the size of the finest subset approaches the theoretical limit.

Brightness Prediction of Large Color Gamut Laser Display Devices.

A brightness-perceived color appearance model tailored for large gamut display devices, exemplified by laser displays, was investigated. Psychophysical experiments on the brightness matching of 30 color stimuli with achromatic white light were conducted by 16 observers. The analysis compares the performance of a number of existing color appearance models and equivalent luminance models in predicting brightness. None of the models performed acceptably due to a severe underestimation of the Helmholtz-Kohlrausch (H-K) effect. A modified model of perceived brightness based on CAM16, taking into account the H-K effect, is proposed. Evaluated by psychophysical experiments, the proposed model exhibits a superior performance compared to the preceding models, especially within the extensive color gamut range stipulated by BT.2020. The results help to optimize the design of laser displays with a wide color gamut and high perceived brightness.

ITGB5 mutation discovered in a Chinese family with blepharophimosis-ptosis-epicanthus inversus syndrome.

Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a rare autosomal-dominant genetic disorder, and mutations in the forkhead box L2 (FOXL2) gene are one of the major genetic causes. As this study shows, there are many patients with BPES who do not have FOXL2 mutations, as the screening results in all family members were negative. Using whole-exome sequence analysis, we discovered another possible mutational cause of BPES in integrin subunit beta 5 (ITGB5). The ITGB5 mutation (c.608T>C, p.Ile203Thr) appears in the base sequence of all BPES+ patients in this family, and it appears to be a three-generation-inherited mutation. It can cause changes in base sequence and protein function, and there may be cosegregation of disease phenotypes. ITGB5 is located on the long arm of chromosome three (3q21.2) and is close to the known pathogenic gene FOXL2 (3q23). This study is the first to report ITGB5 mutations in BPES, and we speculate that it may be directly involved in the pathogenesis of BPES or indirectly through the regulation of FOXL2.

Aberrant amplitude low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) in generalized anxiety disorder (GAD) and their roles in predicting treatment remission.

BACKGROUND: Generalized anxiety disorder (GAD) is a common affective disorder characterized by comprehensive anxiety with dysregulation of brain activity which can be reflected by functional magnetic resonance imaging (f-MRI). We aimed to examine abnormal aberrant amplitude low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) in GAD and evaluate their ability to predict treatment remission. METHODS: Using resting-state fMRI (Rs-fMRI), we examined ALFF and ReHo in 30 GAD patients and 30 healthy control (HC) participants. Using on DEPASF4.3 Advanced Edition, voxel-based two-sample t-test analysis was performed on the ALFF and ReHo maps to compare GAD to HC groups, and to compare remitters (n=9) and non-remitters (n=21). Pearson's correlation analysis was used to explore the relationship between baseline Hamilton Anxiety Rating Scale (HAM-A) scores/illness duration and mean ALFF/ReHo values. The severity of GAD symptoms was rated with HAM-A. Remission was defined as HAM-A ≤7 by week 8. RESULTS: Compared to the HC group, GAD patients showed lower ALFF in the right postcentral and right precentral gyrus; lower ReHo in the right precentral, right postcentral, and left precentral gyrus; and higher ReHo in the left posterior cingulate cortex. ALFF values for left postcentral gyrus was negatively correlated with baseline HAM-A, while that of the middle frontal gyrus was positively correlated with baseline HAM-A scores. ReHo value of the left postcentral gyrus was negatively correlated with baseline HAM-A, while that of the right middle frontal gyrus was positively correlated with baseline HAM-A scores. ALFF of the right frontal_superior_orbital and right frontal-medial-orbital cortex was positively correlated with illness duration. ReHo of the left supplementary motor area cortex was negatively correlated with illness duration. Remitters showed higher ALFF in the left hippocampus and higher ReHo value in the right postcentral cortex compared to nonremitters. CONCLUSIONS: These results suggest that altered regional brain activity and local synchronization may be related to the pathophysiology of GAD and have certain value in predicting remission in treatment.

Acceleration and expansion of a photorealistic computer-generated hologram using backward ray tracing and multiple off-axis wavefront recording plane methods.

Holograms can reconstruct the light wave field of three-dimensional objects. However, the computer-generated hologram (CGH) requires much calculating time. Here we proposed a CGH generation algorithm based on backward ray tracing and multiple off-axis wavefront recording planes (MO-WRP) to generate photorealistic CGH with a large reconstruction image. In this method, multiple WRPs were placed parallelly between the virtual object and the hologram plane. Virtual rays were emitted from the pixel of WRPs and intersect with the object. The complex amplitude of WRPs is then determined by illumination module, such as Phong reflection module. The CGH was generated by the shifted Angular Spectrum Propagation (ASP) from WRPs to the hologram plane. Experimental results demonstrate the effectiveness of this method, and the CGH generation rate is 37.3 frames per second (1 WRP) and 9.8 frames per second (2×2 WRPs).

The association of catechol-O-methyltransferase (COMT) rs4680 polymorphisms and generalized anxiety disorder in the Chinese Han population.

The catechol-O-methyltransferase (COMT) Val158Met polymorphism has been reported to be implicated in generalized anxiety disorder (GAD) as well as the treatment response to antidepressants in patients with GAD, but the findings are inconsistent. In this study, we explore the association among COMT, GAD, and the antidepressant response in the Chinese Han population. One hundred and two patients with GAD and 120 healthy controls (HC) were recruited. All the patients were treated with escitalopram or venlafaxine for 8 weeks. The Hamilton Rating Scale for Anxiety (HAMA) was used to assess the treatment response. All the participants were genotyped for the COMT Val158Met polymorphism using the polymerase chain reaction method. No significant differences in the frequency of the COMT rs4680 polymorphism were found between the GAD and HC groups, or between patients with different genders. Further, we found no significant correlation between the COMT rs4680 polymorphism, gender, and the antidepressant treatment outcomes after eight weeks in the GAD patients. This study indicated that the COMT rs4680 genotype might not be related to GAD or to the genders of the GAD patients, nor did it have any effect on the antidepressant therapeutic response in the GAD patients. Even so, our research will be helpful by providing guidance and direction for future, more in depth, research.

The roles of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) in predicting treatment remission in a Chinese Han population with generalized anxiety disorder.

Neurotrophic factors, particularly brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF), are involved in neuroplasticity in the nervous system. To explore the characteristics of BDNF and GDNF and their roles in predicting treatment remission in a Chinese Han population with generalized anxiety disorder (GAD), 85 GAD patients were treated with escitalopram or venlafaxine randomly for 8 weeks. The serum BDNF/GDNF levels were detected, while Hamilton Anxiety Rating Scale (HAMA) scores were measured at baseline and after 8 weeks of treatment. The differences in serum BDNF/GDNF levels between GAD patients (n = 85) and healthy controls (n = 73) and between remission and nonremission were then compared. The serum BDNF levels were lower in GAD patients (1197.24 ±â€¯367.41 µg/L) than in healthy controls (1378.09 ±â€¯382.46 µg/L) (P < 0.05). The serum GDNF levels were also lower in GAD patients (10.19 ±â€¯9.86 µg/L) than in healthy controls (13.73 ±â€¯9.44 µg/L) (P < 0.05). The BDNF level was negatively correlated with baseline HAMA score (P < 0.05). The GDNF level was negatively correlated with baseline HAMA score (P < 0.05). The BDNF level was positively correlated with GDNF level (P < 0.05). Both baseline BDNF/GDNF levels in remission and nonremission showed no statistically significant differences. No significant correlation was found between baseline BDNF level and the HAMA reduction rate or between baseline GDNF levels and the HAMA reduction rate. Both serum BDNF and GDNF were demonstrated to be potential biomarkers of GAD, it seems that serum BDNF and GDNF levels can be used to assess the baseline anxiety severity of GAD but cannot serve as a factor to predict treatment remission.

Association of NPSR1 rs324981 polymorphism and treatment response to antidepressants in Chinese Han population with generalized anxiety disorder.

In previous studies, neuropeptide S (NPS) and its cognate receptor (NPSR) have been involved in the pathogenesis of anxiety disorders in previous studies. Here, we aimed to investigate the association of NPSR1 polymorphism with generalized anxiety disorder (GAD) and its treatment response in Chinese Han population. Three hundred and thirty seven patients and one hundred and seventy seven healthy controls were involved in our study for 8 weeks. Further, Hamilton Anxiety Scale (HAMA) was used to assess anxiety symptom at baseline and the 1st, 2nd, 4th, 8th week. And all participants were genotyped for NPSR1 (rs324981) variants by polymerase chain reaction. Using Repeated-measures analysis, it showed significant reduction on HAMA scores in patients treated with escitalopram (F = 1.03, P = 0.362) and venlafaxine (F = 0.27, P = 0.763) respectively through 8 weeks treatment. Additionally, patients with AA and TT homozygous genotypes treated with venlafaxine XR had a higher reduction of HAMA scores compared to AT heterozygotic carriers (F = 4.18, P = 0.004), while no significant differences were found in patients treated with escitalopram (F = 1.05, P = 0.383). Thus, our study provides preliminary evidence that NPSR1 AA and TT homozygous genotypes have better treatment responses to venlafaxine XR in Chinese GAD patients, but not to escitalopram. Further studies are needed to verify the observation.

Association Analysis of the Brain-Derived Neurotrophic Factor Gene Val66Met Polymorphism and Gender with Efficacy of Antidepressants in the Chinese Han Population with Generalized Anxiety Disorder.

BACKGROUND AND AIM: This study was designed to explore the relationship between the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and antidepressants' efficacy in the Chinese Han population with generalized anxiety disorder (GAD). MATERIALS AND METHODS: We recruited 206 patients who met the diagnostic criteria for GAD into the test group, and assigned 209 healthy participants to the control group. All participants were genotyped for the BDNF Val66Met polymorphism. GAD patients were treated with escitalopram or extended-release venlafaxine. We used the Hamilton Rating Scale for Anxiety (HAM-A) to assess the response to 8-weeks of antidepressant treatment for GAD. RESULTS: We did not identify any significant differences in the allelic or genotype frequencies of the BDNF Val66Met polymorphism between the test and control group. Furthermore, we did not detect any significant difference in the allele or genotype frequency of BDNF Val66Met between patients with different treatment responses. Finally, we did not detect any significant difference in the HAM-A score reduction rate among patients with different genotypes, gender, or treatment drugs. CONCLUSIONS: No significant difference was found in the BDNF Val66Met polymorphism between patients with GAD and healthy controls, nor was this polymorphism significantly associated with antidepressant drug efficacy for GAD.

Electrical resistivity-based study of self-sensing properties for shape memory alloy-actuated artificial muscle.

Shape memory alloy (SMA) has great potential to develop light and compact artificial muscle (AM) due to its muscle-like high power-to-weight ratio, flexibility and silent operation properties. In this paper, SMA self-sensing properties are explored and modeled in depth to imitate the integrated muscle-like functions of actuating and self-sensing for SMA-AM based on the investigation of SMA electrical resistivity (ER). Firstly, an ER transformation kinetics model is proposed based on the simulation of SMA differential scanning calorimetry (DSC) curves. Then a series of thermal-electrical-mechanical experiments are carried out to verify the validity of the ER model, whereby the SMA-AM self-sensing function is well established under different stress conditions. Finally the self-sensing capability is further demonstrated by its application to a novel SMA-AM-actuated active ankle-foot orthosis (AAFO).

[Virus spectrum features of adult influenza-like fever in outpatients].

OBJECTIVE: To analyze the results of detection on respiratory virus of influenza-like illness ( ILI ) in Beijing from June 2010 to February 2012 and understand the virus spectrum of adult influenza-like fever. METHODS: A total of 502 swabs were collected and 279 throat swabs tested for 12 respiratory viruses with multiplex reverse transcription-polymerase chain reaction (RT-PCR). And 413 swabs were tested for pH1N1 by virus isolation influenza viruses. And the data were statistically analyzed. RESULTS: One or two viruses were detected in 26.9% (75/279) of the samples. Influenza A virus (FLU-A) accounted for 85.3% of positive samples and 22.9% (64/279) of ILI tested. The positive rate of other viruses was less than 3.0 %. The positive rates among the following subtypes were: 2.7% (11/413) for pH1N1, 2.4% (10/413) for H3 and 6.5% (27/413) for FLU-B. FLU-A was the predominant virus during the 2010-2011 influenza season and the positive rate peaked in January 2011 in Beijing and north China. FLU-B was the primary virus during the 2011-2012 influenza season and the positive rate peaked in January and February 2012. There was a significant reduction in the incidence of ILI in 2010 and 2011 when compared with 2009. During the 2009-2012 influenza seasons, the incidence peaked in December 2009, January 2011 and January and February 2012 in Beijing. CONCLUSIONS: Exposure to pH1N1 had no impact on typical influenza seasonal peaks. Influenza virus was the predominant virus of adult influenza-like fever cases after the pandemic period of influenza A (H1N1) 2009 and the positive rate peaked in January and February during the 2009-2012 influenza seasons.

Ag/AgBr/Co-Ni-NO3 layered double hydroxide nanocomposites with highly adsorptive and photocatalytic properties.

A facile anion-exchange precipitation method was used to synthesize bifunctional Ag/AgBr/Co-Ni-NO(3) layered double hydroxide (LDH) nanocomposites by adding AgNO(3) solution to a suspension of Co-Ni-Br LDH. The Ag/AgBr nanoparticles were highly dispersed on the sheets of Co-Ni-NO(3) LDH. The prepared nanocomposites were used to adsorb and photocatalytically degrade organic pollutants from water. Without light illumination, the nanocomposites quickly adsorbed methyl orange, and the adsorptive capacity, which can reach 230 mg g(-1), is much higher than those of Co-Ni-Br LDH, Ag/AgBr, and activated carbon. The photocatalytic activities of the nanocomposites for the removal of dyes and phenol are higher than those of Co-Ni-Br LDH and Ag/AgBr. The proposed method can be applied to prepare other LDH/silver salt composites. The high absorptive capacity and good photocatalytic activity of such nanostructures could have wide applications in wastewater treatment.

Multifunctional Fe3O4 core/Ni-Al layered double hydroxides shell nanospheres as labels for ultrasensitive electrochemical immunoassay of subgroup J of avian leukosis virus.

A novel electrochemical immunosensor for ultrasensitive detection of subgroup J of avian leukosis virus (ALVs-J) was designed by using graphene sheets (GS)-layered double hydroxides (LDHs) composites modified electrode with multifunctional Fe(3)O(4) core/Ni-Al LDHs shell (LDHs@Fe(3)O(4)) nanospheres as labels. At first, the GS-LDHs were used for the immunosensor platform for improving the electronic transmission rate as well as increasing the surface area to capture a large amount of primary antibodies (Ab(1)). After that, ferrocene (Fc), secondary antibodies (Ab(2)) and horseradish peroxidase (HRP) multifunctional LDHs@Fe(3)O(4) nanospheres were used as labels with high load amount and good biological activity. Subsequently, in presence of H(2)O(2), amplified signals were obtained by an electrochemical sandwich immunoassay protocol. To embody the signal amplification property of the protocol, the analytical properties of various immunosensor platform and labels were compared in detail. Under optimal conditions, the reduction peak currents of the electrochemical immunosensor were proportional to the ALVs-J concentration over the range from 10(2.32) to 10(5.50) TCID(50)/mL with a low detection limit (180 TCID(50)/mL, S/N=3). The resulting immunosensor also displayed a good selectivity, reproducibility and stability.

Job satisfaction and intention to leave: a questionnaire survey of hospital nurses in Shanghai of China.

AIM: To explore nurses' views and experiences regarding job satisfaction and their intention to leave in Shanghai. BACKGROUND: The widespread nursing shortage and nurses' high turnover rate has become a global issue. Job satisfaction is the most consistent predictor of nurses' intention to leave and has been reported as explaining most of the variance on their intention to leave. DESIGN: A cross-sectional survey. METHODS: A convenience sample of nurses was recruited from 19 large general hospitals in Shanghai and the research assistants distributed 2850 questionnaires to nurses. The response rate of this study was 78·95%, and 2250 nurses completed the questionnaire. RESULTS: Regarding the overall job satisfaction, 50·2% nurses were dissatisfied and 40·4% nurses reported that they had intention to leave the current employment. Respondents' characteristics had an impact on job satisfaction and their intention to leave. The results showed that age, marital status, work experience, overall job satisfaction, job satisfaction: extrinsic rewards, interaction, praise/recognition and control/responsibility were significant factors contributing to nurses' intention to leave. CONCLUSIONS: The finding may be a cause of concern for hospital management and highlights the importance of the two concepts (job satisfaction and intention to leave) in Shanghai. Innovative and adaptable managerial interventions need to be taken to improve nurses' job satisfaction and to strengthen their intention to stay. RELEVANCE TO CLINICAL PRACTICE: Our findings outline some issues contributing to these problems and provide nurse administrators with information regarding specific influences on nurses' job satisfaction and intention to leave in Shanghai and innovative and adaptable managerial interventions that are needed. Our findings may also provide direction for nurse managers and healthcare management to implement strategies to improve nurses' job satisfaction and their intention to stay.

[Etiological study on sporadic viral gastroenteritis among adult in Beijing].

OBJECTIVE: To understand the infection and epidemiology of norovirus and rotavirus and enteral adenovirus among adult with sporadic viral gastroenteritis in Beijing and provide theoretical basis for clinical prevention and control. METHODS: Stool specimens were collected from all 312 sporadic outpatient among adult with non-cholera watery diarrhea in Infectious Disease Department of Peking University People's Hospital 2005-2006. PAGE were used for detection of rotavirus RNA in stool specimens; R-Biopharm RIDASCREEN norovirus and RIDASCREEN adenovirus were used for detection of norovirus and adenovirus. RESULTS: Rotavirus RNA was not present in all 312 stool specimens; Norovirus was present in 17.6% (22/125) and in 32.4% (11/34) in October; Adenovirus was present in 3.3% (3/92); Mixed infections of norovirus and adenovirus was present in 1 stool specimen. CONCLUSIONS: Norovirus is more common etiologic agents of sporadic acute viral gastroenteritis among adult in Beijing, The infection peak of norovirus is in autumn. Maybe the infection of rotavirus is few.

[Screening analysis of irregular antibodies from random donor population in Shaoguan area].

The study was purposed to analyze the frequency and distribution of irregular antibodies in Shaoguan area. Screening 15 033 random donor antibodies in Shaoguan area by screening cells, polybrene and antiglobulin tests. The results indicated that the irregular antibodies were found in 42 samples. The frequency of irregular antibodies in female was higher than that in male (P < 0.001), and Rh blood group antibodies such as anti-D, anti-E, and anti-Ec C were common (47.6%). 2 samples of Le antibodies were failed to be found by polybrene test. 2 samples of irregular antibodies with titer 2 were undiscovered by screening test of 10 pooled samples. In conclusion, because of irregular antibodies resulting in hemolytic transfusion reaction, the investigation of frequency and distribution of irregular antibodies is very important for safe transfusion. Antibody screening must be done for female donors, and especially for massive plasma transfusion of patients with severe and dangerous illness and infants so as to ensure safety.

[Study on blood ABO typing in patients with autoimmune hemolytic anemia].

To explore effect of autoantibody on identification of ABO and RhD blood group, the blood samples of 38 patients with autoimmune hemolytic anemia (AIHA) were identified by routine typing and typing after chloroquine elution test as well as PCR. The results showed that out of 38 patients with AIHA, 11 cases (31.6%) of ABO blood group were difficulty typed, indirect antiglobulin test were positive, and contradiction between cells typing and sera typing were observed. 1 case of RhD(-) was mistyped as RhD(+) and anti-D was found in its serum. The blood group of these cases were typed correctly by chloroquine elution test. It is concluded that blood group identification of patients with AIHA can be interfered by autoantibody, and the correct typing for blood group of these patients may be determined by using combination of several methods to ensure safe transfusion.