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This study aimed to examine the efficacy of combining paroxetine and mirtazapine v. switching to mirtazapine, for patients with major depressive disorder (MDD) who have had an insufficient response to SSRI monotherapy (paroxetine) after the first 2 weeks of treatment.
This double-blind, randomized, placebo-controlled, three-arm study recruited participants from five hospitals in China. Eligible participants were aged 18–60 years with MDD of at least moderate severity. Participants received paroxetine during a 2-week open-label phase and patients who had not achieved early improvement were randomized to paroxetine, mirtazapine or paroxetine combined with mirtazapine for 6 weeks. The primary outcome was improvement on the Hamilton Rating Scale for Depression 17-item (HAMD-17) scores 6 weeks after randomization.
A total of 204 patients who showed early non-response to paroxetine monotherapy were randomly assigned to receive either mirtazapine and placebo (n = 68), paroxetine and placebo (n = 68) or mirtazapine and paroxetine (n = 68), with 164 patients completing the outcome assessment. At week 8, the least squares (LS) mean change of HAMD-17 scores did not significantly differ among the three groups, (12.98 points) in the mirtazapine group, (12.50 points) in the paroxetine group and (13.27 points) in the mirtazapine plus paroxetine combination group. Participants in the paroxetine monotherapy group were least likely to experience adverse effects.
After 8 weeks follow-up, paroxetine monotherapy, mirtazapine monotherapy and paroxetine/mirtazapine combination therapy were equally effective in non-improvers at 2 weeks. The results of this trial do not support a recommendation to routinely offer additional treatment or a switch in treatment strategies for MDD patients who do not show early improvement after 2 weeks of antidepressant treatment.
Identifying risk factors and mortality of individuals with Alzheimer’s disease (AD) could have important implications for the clinical management of AD.
This pilot study aimed to examine the overall mortality of AD patients over a 10-year surveillance period in Shanghai, China. This study is an extension of our previous investigation on mortality of neurodegenerative diseases.
One hundred and thirty-two AD patients recruited from the memory clinics of two hospitals in Shanghai in 2007 were followed up until December 31, 2017 or death, representing a follow-up period of up to 10 years. Overall standardized mortality ratios (SMRs) were calculated, and predictors for survival at recruitment were estimated.
Sixty-seven patients had died by December 31, 2017, and the SMR at 10 years of follow-up was 1.225 (95% confidence interval 0.944–1.563). Employing Cox’s proportional hazard modeling, lower Mini-Mental State Examination score, and comorbid diabetes predicted poor survival in this cohort.
This pilot study suggests a similar survival trend of patients with AD compared to the general population in Shanghai urban region. Poor cognitive status and comorbid diabetes had a negative impact on the survival of AD patients.
Information on the geographic distribution of a species is fundamental for its conservation. Nonggang Babbler Stachyris nonggangensis (NB) is a rare and newly discovered species that is restricted to limestone karst forest on the Sino-Vietnamese border and has been classified as ‘Vulnerable’ due to its narrow distribution. However, the extent of the habitat suitable for NB is poorly known. We conducted a species distribution model (SDM) using 33 occurrence data and nine environmental variables. The SDM suggested highly suitable habitat covers 541 km2, and habitat with a medium and low level of suitability covers 3,218 km2 and 722 km2, respectively. Of the entire suitable habitat (low through high), 25.8% is in northern Vietnam and the rest is in Guangxi Zhuang Autonomous Region, southern China (especially concentrated in northern Longzhou and southern Daxing Counties). Unfortunately, only 12.4% of the entire suitable habitat is known to be occupied, and the habitat outside the reserves is highly threatened by fragmentation and degradation. Globally, NB is apparently isolated in only four sites, including one site in which we discovered its presence during field validation of the model. Based on this work, we suggest upgrading NB to the ‘Endangered’ category on the IUCN Red List and adding it to the list of endangered species of both China and Vietnam.
In the era of knowledge networking, the structure and production mode of knowledge are constantly changing. This article creatively introduces the knowledge mapping method in design research, and based on the perspective of the National Natural Science Foundation of China (NSFC) to compile literature, uses word frequency analysis, co-word analysis, and citation analysis to construct knowledge graphs of design science. This study graphically shows the distribution and flow law of knowledge within design discipline and probes into the research frontier and evolution trend of Chinese design science.
The secondary instabilities of stationary cross-flow vortices in a Mach 6 swept wing flow are studied using Floquet theory. High-frequency secondary instability modes of ‘y’ mode on top of stationary cross-flow vortices, and ‘z’ mode concentrating on the shoulder of the stationary cross-flow vortex are found. The most unstable secondary instability mode is always the ‘z’ mode as in incompressible swept wing flows. A new secondary instability mode concentrating on the trough of the stationary cross-flow vortex is found. The balance analysis of disturbance kinetic energy shows that the new mode belongs to the class of ‘y’ mode. The growth rate of the new ‘y’ mode located on the trough of the stationary cross-flow vortex is significantly larger than that of the ‘y’ mode on top of the stationary cross-flow vortex, and is comparable with the growth rate of the ‘z’ mode. It is also found that the new ‘y’ mode with higher frequency can evolve into the ‘z’ mode further downstream. The role of the pressure fluctuation term, including the pressure diffusion and pressure dilatation, in the energy production of secondary instability modes, is also investigated. It is shown that the pressure diffusion will only enhance the growth rate of the ‘z’ mode with higher frequency, but has little influence on other types of secondary instability mode. However, the pressure dilatation term arising from non-vanishing velocity divergence will reduce the growth rates of all secondary instability modes.
Employing atomic-scale simulations, the response of a high-angle grain boundary (GB), the soft/hard GB, against external loading was systematically investigated. Under tensile loading close to the hard orientation, strain-induced dynamic recrystallization was observed to initiate through direct soft-to-hard grain reorientation, which was triggered by stress mismatch, inhibited by surface tension from the soft-hard GB, and proceeded by interface ledges. Such grain reorientation corresponds with expansion and contraction of the hard grain along and perpendicular to the loading direction, respectively, accompanied by local atomic shuffling, providing relatively large normal strain of 8.3% with activation energy of 0.04 eV per atom. Tensile strain and residual dislocations on the hard/soft GB facilitate the initiation of dynamic recrystallization by lowering the energy barrier and the critical stress for grain reorientation, respectively.
Identifying the relative importance of urban and non-urban land-use types for potential denitrification derived N2O at a regional scale is critical for quantifying the impacts of human activities on nitrous oxide (N2O) emission under changing environments. In this study we used a regional dataset from China including 197 soil samples and six land-use types to evaluate the main predictors (land use, heavy metals, soil pH, soil moisture, substrate availability, functional and broad microbial abundances) of potential denitrification using multivariate and pathway analysis. Our results provide empirical evidence that soils on farms have the greatest potential denitrifying ability (PDA) (10.92±6.08ng N2O-N·g–1 dry soil·min–1) followed by urban soil (6.80±5.35ng N2O-N·g–1 dry soil·min–1). Our models indicate that land use (low vs. high human activity), followed by total nitrogen (TN) and heavy metals (Cu, Zn, Pb, Cd) was the most important driver of PDA. In addition, our path analysis suggests that at least part of the impacts of land use on potential denitrification were mediated via microbial abundance, soil pH and substrates including TN, dissolved organic carbon and nitrate. This study identifies the main predictors of denitrification at a regional scale which is needed to quantify the impact of human activities on ecosystem functionality under changing conditions.
Ti–Al alloys are established as promising candidates for aerospace applications due to their lightweight, good elevated temperature strength, and decent corrosion resistance. In this study, a Ti–51Al (at.%) alloy is fabricated by spray deposition. The effects of temperature and strain rate on the deformation behavior of the spray-deposited Ti–Al alloy are investigated. The microstructural evolution of the Ti–Al alloy with different deformation temperatures is discussed in detail. A strain-dependent constitutive equation was proposed to predict the flow stresses at the elevated temperatures for the spray-deposited Ti–Al alloy. The microstructure of the as-deposited Ti–51Al alloy exhibits a α2/γ lamellar-structure with average size 25 ± 2 μm, due to the high cooling rate observed during solidification. The lamellar structure is embedded on a γ matrix. The amount of the α2/γ lamellar-structure reduces gradually with increasing the hot deformation temperature. After hot isostatic pressing at 1523 K, the microstructure is mainly comprised of the γ matrix.
Markley variables have advantages of slow variation, easy numerical integration and high precision in describing the attitude of spinning spacecraft. Previous attitude estimation methods based on Markley variables for spinning spacecraft usually employ a sun vector from the sun sensor, a magnetic vector from the magnetometer, or the angular rate from the gyro as the measurement. This paper proposes a Markley variables-based attitude estimation method using optical flow and a star vector from a star sensor as the measurement, where optical flow provides rate information and the star vector provides direction information. This method can estimate the direction of the spin axis and spin angular rate very well by using only one star sensor. In addition, the star sensor has higher accuracy than the traditional sun sensor and magnetometer, and the star sensor can also replace the gyro in case the gyro is out of action. The impact factors of this method are also analysed, which include spin angular rate, spin axis orientation and spacecraft moment of inertia tensor error.
The pathophysiology of cognitive impairment in patients with the major depressive disorder (MDD) may involve neuroinflammation mediated by cytokines.
The aim of this study was to examine the serum interleukin-6 (IL-6) levels, sustained attention, and their association in patients with MDD.
Thirty patients with MDD and 30 healthy controls were enrolled in this case-control study. Sustained attention was measured using the Rapid Visual Information Processing (RVP) task in the Cambridge Neuropsychological Tests Automated Battery. The serum IL-6 levels of all subjects were assessed by sandwich enzyme-linked immunosorbent assays.
There were significant differences in the log10RVP total hits, log10RVP total misses, and log10RVP mean latency between patients with MDD and healthy controls (F = 6.04, p = 0.017; F = 19.77, p < 0.0001; F = 14.42, p < 0.0001, respectively). The serum levels of Log10IL-6 were significantly higher in patients with MDD than in healthy controls (F = 192.27, p < 0.0001). The log10IL-6 levels were also positively correlated with the log10RVP mean latency in patients with MDD (r = 0.45, p = 0.013). A further stepwise multivariate regression analysis indicated that the log10IL-6 levels were significantly associated with the log10RVP mean latency in patients with MDD (β = 0.31, t = 2.41, p = 0.025).
Our data suggested that increased IL-6 levels were associated with the psychopathology of MDD, and that abnormal IL-6 levels were implicated in the impairment of sustained attention in patients with MDD.
We review two recent advances in coupled quantum mechanics/molecular mechanics (QM/MM) modeling for metallic materials. The QM/MM methods are formulated based on quantum mechanical charge density embedding. In the first method, QM/MM coupling is accomplished by an embedding potential evaluated via orbital-free density functional theory. The charge density embedding in the second QM/MM method is achieved through constrained density functional theory. The extension of QM/MM coupling to the quasicontinuum method is illustrated, offering a route toward quantum mechanical simulations of materials at micron scales and beyond. The theoretical formulations of the QM/MM methods are discussed in detail. We also provide some examples where the QM/MM methods have been applied to understand fundamental physics in a wide range of material problems, ranging from void formation, pipe diffusion along dislocation core, nanoindentation of thin films, hydrogen-assisted cracking, magnetism-induced plasticity to stress-controlled catalysis in metals. An outlook to future development of QM/MM methods for metals is envisioned.
In Expt 1, a Zn-unsupplemented basal diet (control) and the basal diet supplemented with one of four different Zn sources, including ZnSO4, Zn-amino acid chelate with a weak chelation strength (Zn-AA W), Zn-protein chelate with a moderate chelation strength (Zn-Pro M) and Zn-protein chelate with a strong chelation strength (Zn-Pro S) were fed to broiler chickens from days 14 to 28. On day 28, Zn content in plasma from the hepatic portal vein increased (P<0·05) in the following order: control<ZnSO4<Zn-AA W<Zn-Pro M<Zn-Pro S. Meanwhile, metallothionein (MT) mRNA levels in the duodenum, jejunum and ileum were enhanced (P<0·05) by Zn addition regardless of Zn source. However, no differences among different Zn sources were observed. In Expt 2, ligated duodenal loops from Zn-deficient broilers (28-d old) were perfused with solutions containing 0–2·464 mmol Zn/l from the above-mentioned four Zn sources for up to 30 min. The uptake kinetics of Zn followed a saturable carrier-mediated process. The maximum absorption velocity values were in the following order: control<ZnSO4<Zn-AA W<Zn-Pro M<Zn-Pro S. Moreover, MT mRNA levels for Zn-Pro S (P<0·03), Zn-Pro M (P>0·05) and Zn-AA W(P<0·04) were higher than those for ZnSO4. These findings indicate that organic Zn absorption (especially Zn-Pro S) in intact living broilers was more effective than that of inorganic Zn; organic Zn absorption in the ligated duodenal segment was a saturable carrier-mediated process similar to that of ZnSO4. Moreover, except for MT, there might be other Zn transporters involved in Zn absorption that are affected by different Zn sources.
Preference-based measures of health-related quality of life play a key role in the calculation of Quality-Adjusted Life Years (QALYs) for Health Technology Assessment (HTA). The Child Health Utility 9D (CHU9D) is a new preference-based instrument designed specifically for application in children and adolescents (aged 7 to 17 years). This study aimed to compare Chinese and Australian adolescent population preferences for CHU9D health states using profile case best worst scaling (BWS) methods.
Fifty CHU9D health states (blocked into five survey versions) were generated for valuation using a fractional factorial design. Study participants were recruited through an online panel company in Australia, and through primary and secondary schools in China. A latent class modelling framework was adopted for econometric analysis.
A total of 1,982 respondents (51 percent female) in Australia and 902 respondents (43 percent female) in China provided useable survey responses. Latent class analysis indicated the existence of preference heterogeneity for both population groups. In the Australian sample, respondents in Class I placed the most importance on the mental health dimensions of the CHU9D (for example, Worried and Annoyed) and the least importance on daily activities (for example, Activities, Daily routine, Sleep), whilst respondents in Class II placed equal weights on all attributes. In the Chinese sample, respondents in Class I placed the most importance on the Activities dimension of the CHU9D and the least importance on the Annoyed dimension, whist Class II placed the most importance on the Schoolwork dimension and the least importance on Pain.
This study has provided important cross-country insights into the use of profile case BWS methods to elicit health state preferences with young people for application in HTA in children and adolescents. The differential latent classes identified between Australia and China highlights the necessity to derive country-specific adolescent scoring algorithms for the CHU9D instrument for application in HTA.
To investigate the effect of Mn on antioxidant status and on the expressions of heat shock proteins/factors in tissues of laying broiler breeders subjected to heat challenge, we used a completely randomised design (n 6) with a factorial arrangement of 2 environmental temperatures (normal, 21±1°C, and high, 32±1°C)×3 dietary Mn treatments (a Mn-unsupplemented basal diet (CON), or a basal diet supplemented with 120 mg Mn/kg diet, either as inorganic Mn sulphate (iMn) or as organic Mn proteinate (oMn)). There were no interactions (P>0·10) between environmental temperature and dietary Mn in any of the measured indices. High temperature decreased (P<0·003) Mn content, and also tended (P=0·07) to decrease Cu Zn superoxide dismutase (CuZnSOD) activity in the liver and heart. However, an increased Mn superoxide dismutase (MnSOD) activity (P<0·05) and a slight increase in malondialdehyde level (P=0·06) were detected in breast muscle. Up-regulated (P<0·05) expressions of heat shock factor 1 (HSF1) and HSF3 mRNA and heat shock protein 70 (HSP70) mRNA and protein were found in all three tissues. Broiler breeders fed either iMn or oMn had higher tissue Mn content (P<0·0001), heart MnSOD and CuZnSOD activities (P<0·01) and breast muscle MnSOD protein levels (P<0·05), and lower (P<0·05) breast muscle HSP70 mRNA and protein levels compared with those fed CON. Broiler breeders fed oMn had higher (P<0·03) bone Mn content than those fed iMn. These results indicate that high temperature decreases Mn retention and increases HSP70, HSF1 and HSF3 expressions in the tissues of laying broiler breeders. Furthermore, dietary supplementation with Mn in either source may enhance the heart’s antioxidant ability and inhibit the expression of HSP70 in breast muscle. Finally, the organic Mn appears to be more available than inorganic Mn for bone in laying broiler breeders regardless of environmental temperatures.
Correlative light and electron microscopy (CLEM) offers a means of guiding the search for the unique or rare events by fluorescence microscopy (FM) and allows electron microscopy (EM) to zoom in on them for subsequent EM examination in three-dimensions (3D) and with nanometer-scale resolution. FM visualizes the localization of specific antigens by using fluorescent tags or proteins in a large field-of-view to study their cellular function, whereas EM provides the high level of resolution for complex structures. And cryo CLEM combines the advantages of maintaining structural preservation in a near-native state throughout the entire imaging process and by avoiding potentially harmful pre-treatments, such as chemical fixation, dehydration and staining with heavy metals. Besides for frozen-hydrated biological samples, CLEM combines the advantages of a close-to-life preservation of biological materials by keeping them embedded in vitreous ice throughout the entire imaging process and the frozen-hydrated condition is very suitable to maintain fluorescent signals. In recent years, many new instruments and software which intended to optimize the workflow and to obtain better experimental results of CLEM have been presented or even commoditized. While, the specimen damage during transfer from FM to EM and the resolution of CLEM were still need to be improved.
Here we set up a High-vacuum Optical Platform to develop CLEM imaging technology (HOPE), which was designed to realize high-vacuum optical ( fluorescent) imaging for cryo-sample on EM cryo-holder (e.g. Gatan 626). A non-integrated high-vacuum cryo-optical stage, which adapted to the EM cryo holder, was fixed on epi-fluorescence microscope (or super-resolution microscope) to obtain fluorescent images. And then the EM cryo holder would be transferred to EM for collection of EM data. This protocol was aimed to minimize the specimen damage during transfer from FM to EM and it was versatile to expend to different types of light microscopy or electron microscopy. Our HOPE had already passed correlative imaging test, and the results showed that it was convenient and effective.
Accumulating evidence suggests that altered immunity contributes to the
development of major depressive disorder (MDD).
To examine whether complement factor H (CFH), a regulator of activation
of the alternative pathway of the complement cascade, confers
susceptibility to MDD.
Expression analyses were tested in 53 unmedicated people with MDD and 55
healthy controls. A two-stage genetic association analysis was performed
in 3323 Han Chinese with or without MDD. Potential associations between
CFH single nucleotide polymorphisms and age at MDD
onset were evaluated.
CFH levels were significantly lower in the MDD group at
both protein and mRNA levels (P = 0.009 and
P = 0.014 respectively). A regulatory variant in the
CFH gene, rs1061170, showed statistically significant
genotypic and allelic differences between the MDD and control groups
(genotypic P = 0.0005, allelic P =
0.0001). Kaplan–Meier survival analysis showed that age at onset of MDD
was significantly associated with the C allele of
rs1061170 (log rank statistic χ2 = 6.82, P =
0.009). The C-allele carriers had a younger age at onset
of MDD (22.2 years, s.d. = 4.0) than those without the C
allele (23.6 years, s.d. = 4.3).
CFH is likely to play an important role in the
development of MDD. rs1061170 has an important effect on age at onset of
MDD in Han Chinese and may therefore be related to early pathogenesis of
MDD, although further study is needed.
Nanocolloidal crystals (NCCs) have promising applications in optical and photonic devices. However, it is critical to mechanically reinforce NCCs for device reliability, since as-synthesized NCCs are fragile due to weak interparticle bonding. Thermal sintering is currently the most common reinforcement technique; however, this method could induce serious cracking and is not suitable for temperature-sensitive materials. In this study, by characterizing silica NCCs reinforced through sintering and alumina atomic layer deposition (ALD), we find that the ALD treatment is much more effective for hardening, stiffening, and more importantly toughening NCCs. Thermally sintered NCCs are prone to indentation-induced cracking due to large residual tensile stress, significantly impairing the toughness. In contrast, the ALD treatment toughens NCCs by much over 300%. Our finding provides insights for reinforcing and toughening various nanoparticle-based and nanoporous materials.
To investigate the effect of Mn on antioxidant status and expression levels of heat-shock proteins/factors in tissues of laying broiler breeders subjected to heat challenge, we used a completely randomised design (n 6) with a factorial arrangement of 2 environmental temperatures (normal, 21 (sem 1)°C and high, 32 (sem 1)°C)×3 dietary Mn treatments (an Mn-unsupplemented basal diet (CON), or a basal diet supplemented with 120 mg Mn/kg diet as inorganic Mn sulphate (iMn) or organic Mn proteinate (oMn)). There were no interactions (P>0·10) between environmental temperature and dietary Mn in all of the measured indices. High temperature decreased (P<0·003) Mn content, and also tended (P=0·07) to decrease copper zinc superoxide dismutase (CuZnSOD) activity in the liver and heart. However, an increased manganese superoxide dismutase (MnSOD) activity (P<0·05) and a slight increase of malondialdehyde level (P=0·06) were detected in breast muscle. Up-regulated (P<0·05) expression levels of heat-shock factor 1 (HSF1) and HSF3 mRNA and heat-shock protein 70 (HSP70) mRNA and protein were found in all three tissues. Broiler breeders fed either iMn or oMn had higher tissue Mn content (P<0·0001), heart MnSOD and CuZnSOD activities (P<0·01) and breast muscle MnSOD protein levels (P<0·05), and lower (P<0·05) breast muscle HSP70 mRNA and protein levels than those fed CON. Broiler breeders fed oMn had higher (P<0·03) bone Mn content than those fed iMn. These results indicate that high temperature decreases Mn retention and increases HSP70 and HSF1, HSF3 expression levels in tissues of laying broiler breeders. Furthermore, dietary supplementation with Mn in either source may enhance heart antioxidant ability and inhibit the expression of HSP70 in breast muscle. Finally, the organic Mn appears to be more available than inorganic Mn for bone in laying broiler breeders regardless of environmental temperatures.