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Abnormal reward functioning is central to anhedonia and amotivation symptoms of schizophrenia (SCZ). Reward processing encompasses a series of psychological components. This systematic review and meta-analysis examined the brain dysfunction related to reward processing of individuals with SCZ spectrum disorders and risks, covering multiple reward components.
Methods
After a systematic literature search, 37 neuroimaging studies were identified and divided into four groups based on their target psychology components (i.e. reward anticipation, reward consumption, reward learning, effort computation). Whole-brain Seed-based d Mapping (SDM) meta-analyses were conducted for all included studies and each component.
Results
The meta-analysis for all reward-related studies revealed reduced functional activation across the SCZ spectrum in the striatum, orbital frontal cortex, cingulate cortex, and cerebellar areas. Meanwhile, distinct abnormal patterns were found for reward anticipation (decreased activation of the cingulate cortex and striatum), reward consumption (decreased activation of cerebellum IV/V areas, insula and inferior frontal gyri), and reward learning processing (decreased activation of the striatum, thalamus, cerebellar Crus I, cingulate cortex, orbitofrontal cortex, and parietal and occipital areas). Lastly, our qualitative review suggested that decreased activation of the ventral striatum and anterior cingulate cortex was also involved in effort computation.
Conclusions
These results provide deep insights on the component-based neuro-psychopathological mechanisms for anhedonia and amotivation symptoms of the SCZ spectrum.
In this study, the length scaling for the boundary layer separation induced by two incident shock waves is experimentally and analytically investigated. The experiments are performed in a Mach 2.73 flow. A double-wedge shock generator with two deflection angles ($\alpha _1$ and $\alpha _2$) is employed to generate two incident shock waves. Two deflection angle combinations with an identical total deflection angle are adopted: ($\alpha _1 = 7^\circ$, $\alpha _2 = 5^\circ$) and ($\alpha _1 = 5^\circ$, $\alpha _2 = 7^\circ$). For each deflection angle combination, the flow features of the dual-incident shock wave–turbulent boundary layer interactions (dual-ISWTBLIs) under five shock wave distance conditions are examined via schlieren photography, wall-pressure measurements and surface oil-flow visualisation. The experimental results show that the separation point moves downstream with increasing shock wave distance ($d$). For the dual-ISWTBLIs exhibiting a coupling separation state, the upstream interaction length ($L_{int}$) of the separation region approximately linearly decreases with increasing $d$, and the decrease rate of $L_{int}$ with $d$ increases with the second deflection angle under the condition of an identical total deflection angle. Based on control volume analysis of mass and momentum conservations, the relation between $L_{int}$ and $d$ is analytically determined to be approximately linear for the dual-ISWTBLIs with a coupling separation region, and the slope of the linear relation obtained analytically agrees well with that obtained experimentally. Furthermore, a prediction method for $L_{int}$ of the dual-ISWTBLIs with a coupling separation region is proposed, and the relative error of the predicted $L_{int}$ in comparison with the experimental result is $\sim$10 %.
Objectives: Rapid and accurate screening for carbapenemase-producing organism (CPOs) in hospitalized patients is critical for infection control and prevention. The Xpert Carba-R assay is designed for rapid detection of CPOs, but 1 assay is usually conducted for only 1 sample. We evaluated a pooling strategy for CPO screening using the Xpert Carba-R assay. Methods: Swab sets containing 2 swabs were collected from 415 unique patients at Peking University People’s Hospital. One swab was used for the pooling test, in which 5 swabs from different patients were mixed in 1 sample treatment solution. The prevalence of CPOs in the hospital (5.3%) predicted that 5:1 pooling was most economical. As the reference method, the other swab was tested by culture using sequencing. Results: Of 415 samples, 383 were CPO negative using the pooling test strategy and 31 were positive. All samples that were negative by pooling were negative by culture and sequencing. Among the 31 positive samples identified by the pooling strategy, 26 were positive by culture and sequencing (including 24 samples with 1 targeted gene and 2 samples with double targeted genes, 1 NDM+/IMP+ and 1 VIM+/IMP+), and 5 were negative. Overall, 198 tests were conducted in the study, and 217 were saved compared with testing individually. The efficiency of the pooling strategy was 215%. The overall sensitivity was 1 (95% CI, 0.840–1), the specificity was 0.987 (95% CI, 0.968–0.995), the accuracy was 0.987 (95% CI, 0.970–0.996), positive predictive value was 0.838 (95% CI, 0.655–0.939), and the negative predictive value was 1 (95% CI, 0.988–1). Conclusions: The pooling strategy using the Xpert Carba-R assay showed good potential in screening CPO with good sensitivity and a significantly lower cost.
Circulating n-3 PUFA, which integrate endogenous and exogenous n-3 PUFA, can be better used to investigate the relationship between n-3 PUFA and disease. However, studies examining the associations between circulating n-3 PUFA and colorectal cancer (CRC) risk were limited, and the results remained inconclusive. This case–control study aimed to examine the association between serum n-3 PUFA and CRC risk in Chinese population. A total of 680 CRC cases and 680 sex- and age-matched (5-year interval) controls were included. Fatty acids were assayed by GC. OR and 95 % CI were calculated using multivariable logistic regression after adjustment for potential confounders. Higher level of serum α-linolenic acid (ALA), docosapentaenoic acid (DPA), DHA, long-chain n-3 PUFA and total n-3 PUFA were associated with lower odds of CRC. The adjusted OR and 95 % CI were 0·34 (0·24, 0·49, Pfor trend < 0·001) for ALA, 0·57 (0·40, 0·80, Pfor trend < 0·001) for DPA, 0·48 (0·34, 0·68, Pfor trend < 0·001) for DHA, 0·39 (0·27, 0·56, Pfor trend < 0·001) for long-chain n-3 PUFA and 0·31 (0·22, 0·45, Pfor trend < 0·001) for total n-3 PUFA comparing the highest with the lowest quartile. However, there was no statistically significant association between EPA and odds of CRC. Analysis stratified by sex showed that ALA, DHA, long-chain n-3 PUFA and total n-3 PUFA were inversely associated with odds of CRC in both sexes. This study indicated that serum ALA, DPA, DHA, long-chain n-3 PUFA and total n-3 PUFA were inversely associated with odds of having CRC in Chinese population.
Many studies suggest that both psychotherapy and drug therapy are effective in the treatment of bipolar disorders (BDs). However, the pathophysiology of both types of intervention has not been established definitively.
Methods
An activation likelihood estimation meta-analysis was performed to identify the distinct brain activity alterations between psychotherapy and drug therapy for the treatment of BDs. Articles were identified by searching databases including PubMed, Embase, Cochrane Library, and Web of Science databases. Eligible studies on BDs were published up until 10 June 2021.
Results
21 studies were included and we conducted a meta-analysis for different therapies and imaging tasks. After receiving psychotherapy, BD patients showed increased activation in the inferior frontal gyrus (IFG) and superior temporal gyrus. While after taking drug therapy, BD patients displayed increased activation in the anterior cingulate cortex, medial frontal gyrus, IFG, and decreased activation in the posterior cingulate cortex. The regions of brain activity changes caused by psychotherapy were mostly focused on the frontal areas, while drug therapy mainly impacted on the limbic areas. Different type of tasks also affected brain regions which were activated.
Conclusions
Our comprehensive meta-analysis indicates that these two treatments might have effect on BD in their own therapeutic modes. Psychotherapy might have a top-down effect, while drug therapy might have a bottom-up effect. This study may contribute to differential diagnosis of BDs and would be helpful to finding more accurate neuroimaging biomarkers for BD treatment.
This study aimed to determine the ideal pacing site in children by comparing the postoperative ventricular synchrony in children with left bundle branch area pacing and those with right ventricular septal pacing.
Methods:
This retrospective study included children with complete atrioventricular block who underwent permanent pacemaker implantation from March 2019 to August 2021. Patients were grouped according to their ventricular pacing site, the left bundle branch area pacing group and the right ventricular septal pacing group. Two-dimensional speckle tracking echocardiography was used to evaluate the ventricular synchrony.
Results:
Forty-eight children (median age, 2.7 years; interquartile range, 1.7–4.6 years) were included. The paced QRS duration in the left bundle branch area pacing group was significantly narrower than that in the right ventricular septal pacing group (100.2 ± 9.3 versus 115.4 ± 15.1 ms, p = 0.001). The median follow-up duration was 1.5 years (interquartile range, 1–2 years). At the last follow-up, the average capture threshold of the ventricular electrode in the left bundle branch area pacing group was lower than that in the right ventricular septal pacing group (0.79 ± 0.18 versus 1.20 ± 0.56 V, p = 0.008). The left ventricular intraventricular synchrony parameters in the left bundle branch area pacing group were better than those in the right ventricular septal pacing group (e.g. standard deviation of the time to peak longitudinal strain, 37.4 ± 4.3 versus 46.6 ± 8.2 ms, p = 0.000). The average interventricular mechanical delay time in the left bundle branch area pacing group was significantly shorter than that in the right ventricular septal pacing group (36.4 ± 14.2 versus 52.5 ± 22.7 ms, p = 0.016).
Conclusion:
Compared with right ventricular septal pacing, left bundle branch area pacing in children produces a narrower QRS duration and better pacing and ventricular synchrony parameters postoperatively.
Plasma jets are widely investigated both in the laboratory and in nature. Astrophysical objects such as black holes, active galactic nuclei and young stellar objects commonly emit plasma jets in various forms. With the availability of data from plasma jet experiments resembling astrophysical plasma jets, classification of such data would potentially aid in not only investigating the underlying physics of the experiments but also the study of astrophysical jets. In this work we use deep learning to process all of the laboratory plasma images from the Caltech Spheromak Experiment spanning two decades. We found that cosine similarity can aid in feature selection, classify images through comparison of feature vector direction and be used as a loss function for the training of AlexNet for plasma image classification. We also develop a simple vector direction comparison algorithm for binary and multi-class classification. Using our algorithm we demonstrate 93 % accurate binary classification to distinguish unstable columns from stable columns and 92 % accurate five-way classification of a small, labelled data set which includes three classes corresponding to varying levels of kink instability.
Genetic mutations of fused in sarcoma (FUS) causing amyotrophic lateral sclerosis (ALS) may disrupt mRNA splicing events. For example, the FUS c.1394-2delA variant was reported in two western ALS patients, but its molecular mechanism is unclear. In this study, we aim to investigate FUS splice site mutations in Chinese ALS patients.
Methods:
Sanger sequencing was used to identify FUS splicing mutations in Chinese ALS patients. We combined a deep learning tool (SpliceAI), RNA sequencing, and RT-PCR/RT-qPCR to analyze the effect of FUS c.1394-2delA mutation on RNA splicing and expression. AlphaFold was used to predict the protein structure of mutant FUS. In transfected cell lines, we used immunofluorescence to assess cytoplasmic mislocalization of mutant FUS protein.
Results:
We identified a de novo FUS splice acceptor site mutation (c.1394-2delA, p. Gly466Valfs*14) in one Chinese sporadic ALS patient, which is linked to exon 14 skipping, and upregulated total FUS mRNA expression. The FUS splice site mutation was predicted to be translated into a truncated protein product at C-terminal. In vitro studies revealed that the FUS mutation increased cytoplasmic mislocalization in both HEK293T and SH-SY5Y cells.
Conclusions:
We identified a de novo FUS splicing mutation (c.1394-2delA, p. Gly466Valfs*14) in 1 out of 233 Chinese ALS patients. It caused abnormal RNA splicing, upregulated gene expression, truncated FUS translation, and cytosolic mislocalization. Our findings suggested that FUS splice site mutation is rare in Chinese ALS patients and extended our knowledge of molecular mechanisms of the FUS c.1394-2delA mutation.
It remains unclear whether all physical activity (PA) domains (e.g., occupation-related PA [OPA], transportation-related PA [TPA], and leisure-time PA [LTPA]) have equivalent beneficial relationships. We aimed to investigate the associations of OPA, TPA, and LTPA with depressive symptoms in adults.
Methods
We included and analyzed 31,221 participants (aged ≥18 years) from the cross-sectional 2007–2018 U.S. National Health and Nutrition Examination Survey (NHANES). The PA domains were assessed by a self-report questionnaire and categorized based on the PA guidelines. Depressive symptoms were measured by the nine-item Patient Health Questionnaire.
Results
Participants achieving PA guidelines (≥150 min/week) were 26% (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.68–0.80) and 43% (OR 0.57, 95% CI 0.51–0.62) less likely to have depressive symptoms depending on total PA and LTPA, respectively, while OPA or TPA did not demonstrate lower risks of depressive symptoms. LTPA at levels of 1–149, 150–299, and ≥300 min/week was associated with 31% (OR 0.69, 95% CI 0.60–0.78), 43% (OR 0.57, 95% CI 0.49–0.67), and 51% (OR 0.49, 95% CI 0.43–0.55) lower odds of depressive symptoms, respectively.
Conclusion
LTPA, but not OPA or TPA, was associated with a lower risk of depressive symptoms at any amount, suggesting that significant mental health would benefit from increased PA, even at levels below the recommendation.
Hormone-sensitive lipase (HSL) is one of the rate-determining enzymes in the hydrolysis of TAG, playing a crucial role in lipid metabolism. However, the role of HSL-mediated lipolysis in systemic nutrient homoeostasis has not been intensively understood. Therefore, we used CRISPR/Cas9 technique and Hsl inhibitor (HSL-IN-1) to establish hsla-deficient (hsla-/-) and Hsl-inhibited zebrafish models, respectively. As a result, the hsla-/- zebrafish showed retarded growth and reduced oxygen consumption rate, accompanied with higher mRNA expression of the genes related to inflammation and apoptosis in liver and muscle. Furthermore, hsla-/- and HSL-IN-1-treated zebrafish both exhibited severe fat deposition, whereas their expressions of the genes related to lipolysis and fatty acid oxidation were markedly reduced. The TLC results also showed that the dysfunction of Hsl changed the whole-body lipid profile, including increasing the content of TG and decreasing the proportion of phospholipids. In addition, the systemic metabolic pattern was remodelled in hsla-/- and HSL-IN-1-treated zebrafish. The dysfunction of Hsl lowered the glycogen content in liver and muscle and enhanced the utilisation of glucose plus the expressions of glucose transporter and glycolysis genes. Besides, the whole-body protein content had significantly decreased in the hsla-/- and HSL-IN-1-treated zebrafish, accompanied with the lower activation of the mTOR pathway and enhanced protein and amino acid catabolism. Taken together, Hsl plays an essential role in energy homoeostasis, and its dysfunction would cause the disturbance of lipid catabolism but enhanced breakdown of glycogen and protein for energy compensation.
We report dispersion management based on a mismatched-grating compressor for a 100 PW level laser, which utilizes optical parametric chirped pulse amplification and also features large chirped pulse duration and an ultra-broadband spectrum. The numerical calculation indicates that amplified pulses with 4 ns chirped pulse duration and 210 nm spectral bandwidth can be directly compressed to sub-13 fs, which is close to the Fourier-transform limit (FTL). More importantly, the tolerances of the mismatched-grating compressor to the misalignment of the stretcher, the error of the desired grating groove density and the variation of material dispersion are comprehensively analyzed, which is crucially important for its practical application. The results demonstrate that good tolerances and near-FTL compressed pulses can be achieved simultaneously, just by keeping a balance between the residual second-, third- and fourth-order dispersions in the laser system. This work can offer a meaningful guideline for the design and construction of 100 PW level lasers.
This research communication investigated the role and the underlying mechanism of sn-1-acylglycerol-3-phosphate O-acyltransferase 6 (AGPAT6) in acetate-induced mTORC1 signaling activation and milk fat synthesis in dairy cow mammary epithelial cells. The data showed AGPAT6 knockdown significantly decreased acetate-induced phosphorylation of mTORC1 signaling molecules and intracellular triacylglycerol (TAG) content, whereas this inhibition effect was reversed after the addition of 16:0,18:1 phosphatidic acid (PA), suggesting that AGPAT6 could generate PA in response to acetate simulation, that in turn activates mTORC1 signaling. PPARγ is the upstream regulator of AGPAT6 upon acetate stimulation. Luciferase assay with clones containing various deletions and mutation in AGPAT6 promoter showed that there is a RXRα binding sequence located at −96 bp of AGPAT6 promoter. Acetate stimulation significantly increased the interaction between PPARγ and AGPAT6 via this RXRα binding site. Taken together, our data indicated that AGPAT6 could activate mTORC1 signaling by producing PA during acetate-induced milk fat synthesis, and PPARγ acts as a transcription factor to mediate the effect of acetate on AGPAT6 via RXRα.
High-molecular-weight glutenin subunits (HMW-GS) contribute to dough elasticity and bread baking quality in wheat. In this study, wheat varieties were classified based on their HMW-GS composition into three groups: 1Dx5 (5 + 10, Gaoyou 8901, Xinmai 28, Xinmai 19, Xinmai 26 and Jinbaoyin), 1Dx2 (2 + 12, Zhoumai 24, Xinmai 9 and Yumai) and 1Dx4 (4 + 12, Aikang 58). Sequence analysis showed that 1Dx-GY8901, 1Dx-XM28, 1Dx-XM19 and 1Dx-XM26 were similar to the 1Dx5 gene and clustered on the same branch, while 1Dx-AK58, 1Dx-ZM24, 1Dx-JBY, 1Dx-YM, 1Dx-XM9 and 1Dx-JBY were more similar to the 1Dx2 gene and clustered on the same branch with 1Dx.2.2. There was a mutation of Ser to Cys at position S2, for an extra Cys in the repeat regions of 1Dx-XM19, 1Dx-XM26, 1Dx-XM28 and 1Dx-GY8901. The wheat HMW-GS genes exhibited similar percentages of α-helix, extended strand, β-turn and random coil structure, with ranges of 13.33–13.59, 4.77–5.78, 7.08–9.18 and 72.3–73.94%, respectively. Sequence conservation and the composition of HMW-GS subunits were also analysed for a series of strong gluten wheat varieties, Xinmai 9 (1, 7 + 8, 2 + 12), Xinmai 19 (1, 7 + 9, 5 + 10), Xinmai 26 (1, 7 + 8, 5 + 10) and Xinmai 28 (1, 7 + 9, 5 + 10). The results of this work should facilitate future breeding efforts and provide the theoretical basis for wheat quality improvement.
We present an experimental study of Rayleigh–Bénard convection using liquid metal alloy gallium-indium-tin as the working fluid with a Prandtl number of $Pr=0.029$. The flow state and the heat transport were measured in a Rayleigh number range of $1.2\times 10^{4} \le Ra \le 1.3\times 10^{7}$. The temperature fluctuation at the cell centre is used as a proxy for the flow state. It is found that, as $Ra$ increases from the lower end of the parameter range, the flow evolves from a convection state to an oscillation state, a chaotic state and finally a turbulent state for $Ra>10^5$. The study suggests that the large-scale circulation in the turbulent state is a residual of the cell structure near the onset of convection, which is in contrast with the case of $Pr\sim 1$, where the cell structure is transiently replaced by high order flow modes before the emergence of the large-scale circulation in the turbulent state. The evolution of the flow state is also reflected by the heat transport characterised by the Nusselt number $Nu$ and the probability density function (p.d.f.) of the temperature fluctuation at the cell centre. It is found that the effective local heat transport scaling exponent $\gamma$, i.e. $Nu\sim Ra^{\gamma }$, changes continuously from $\gamma =0.49$ at $Ra\sim 10^4$ to $\gamma =0.25$ for $Ra>10^6$. Meanwhile, the p.d.f. at the cell centre gradually evolves from a Gaussian-like shape before the transition to turbulence to an exponential-like shape in the turbulent state. For $Ra>10^6$, the flow shows self-similar behaviour, which is revealed by the universal shape of the p.d.f. of the temperature fluctuation at the cell centre and a $Nu=0.19Ra^{0.25}$ scaling for the heat transport.
According to Hamilton's rule, matrilineal-biased investment restrains men in matrilineal societies from maximising their inclusive fitness (the ‘matrilineal puzzle'). A recent hypothesis argues that when women breed communally and share household resources, a man should help his sisters' household, rather than his wife's household, as investment to the later but not the former would be diluted by other unrelated members (Wu et al., 2013). According to this hypothesis, a man is less likely to help on his wife's farm when there are more women reproducing in the wife's household, because on average he would be less related to his wife's household. We used a farm-work observational dataset, that we collected in the matrilineal Mosuo in southwest China, to test this hypothesis. As predicted, high levels of communal breeding by women in his wife's households do predict less effort spent by men on their wife's farm, and communal breeding in men's natal households do not affect whether men help on their natal farms. Thus, communal breeding by women dilutes the inclusive fitness benefits men receive from investment to their wife and children, and may drive the evolution of matrilineal-biased investment by men. These results can help solve the ‘matrilineal puzzle'.
It is unclear whether the enhancing contact model (ECM) intervention is effective in reducing family caregiving burden and improving hope and quality of life (QOL) among family caregivers of persons with schizophrenia (FCPWS).
Methods
We conducted a cluster randomized controlled trial in FCPWS in eight rural townships in Xinjin, Chengdu, China. In total, 253 FCPWS were randomly allocated to the ECM, psychoeducational family intervention (PFI), or treatment as usual (TAU) group. FCPWS in three groups were assessed caregiving burden, QOL and state of hope at baseline (T0), post-intervention (T1), 3-month (T2), and 9-month (T3) follow-up, respectively.
Results
Compared with participants in the TAU group, participants in the ECM group had statistically significantly lower caregiving burden scores both at T1 and T2 (p = 0.0059 and 0.0257, respectively). Compared with participants in the TAU group, participants in the PFI group had statistically significantly higher QOL scores in T1 (p = 0.0406), while participants in the ECM group had statistically significantly higher QOL scores in T3 (p = 0.0240). Participants in both ECM and PFI groups had statistically significantly higher hope scores than those in the TAU group at T1 (p = 0.0160 and 0.0486, respectively).
Conclusions
This is the first study to explore the effectiveness of ECM on reducing family caregiving burden and improving hope and QOL in rural China. The results indicate the ECM intervention, a comprehensive and multifaceted intervention, is more effective than the PFI in various aspects of mental wellbeing among FCPWS. Future research needs to confirm ECM's effectiveness in various population.
The relationship of a diet low in fibre with mortality has not been evaluated. This study aims to assess the burden of non-communicable chronic diseases (NCD) attributable to a diet low in fibre globally from 1990 to 2019.
Design:
All data were from the Global Burden of Disease (GBD) Study 2019, in which the mortality, disability-adjusted life-years (DALY) and years lived with disability (YLD) were estimated with Bayesian geospatial regression using data at global, regional and country level acquired from an extensively systematic review.
Setting:
All data sourced from the GBD Study 2019.
Participants:
All age groups for both sexes.
Results:
The age-standardised mortality rates (ASMR) declined in most GBD regions; however, in Southern sub-Saharan Africa, the ASMR increased from 4·07 (95 % uncertainty interval (UI) (2·08, 6·34)) to 4·60 (95 % UI (2·59, 6·90)), and in Central sub-Saharan Africa, the ASMR increased from 7·46 (95 % UI (3·64, 11·90)) to 9·34 (95 % UI (4·69, 15·25)). Uptrends were observed in the age-standardised YLD rates attributable to a diet low in fibre in a number of GBD regions. The burden caused by diabetes mellitus increased in Central Asia, Southern sub-Saharan Africa and Eastern Europe.
Conclusions:
The burdens of disease attributable to a diet low in fibre in Southern sub-Saharan Africa and Central sub-Saharan Africa and the age-standardised YLD rates in a number of GBD regions increased from 1990 to 2019. Therefore, greater efforts are needed to reduce the disease burden caused by a diet low in fibre.