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The previous study indicated that ubiquitination is involved in the freezing tolerance of hydrated seeds. Parthenolide (PN), inducing the ubiquitination of MDM2, an E3 ring-finger ubiquitin ligase, adversely affects the freezing tolerance of hydrated lettuce seeds. Therefore, a proteomics analysis was conducted to identify PN's targets in hydrated seeds exposed to cooling conditions. Several pathways, including oxidative phosphorylation (KEGG00190), amino sugar and nucleotide sugar metabolism (KEGG00520), and biosynthesis of nucleotide sugars (KEGG01250), were enriched in the PN treatment under slow-cooling conditions (3°C h−1, P < 0.05). Among the proteins in oxidative phosphorylation, the expression of NADH dehydrogenases and ATP synthases (ATPsyn) decreased in PN treatment. In contrast, uncoupling proteins increased after PN treatment, which led to the dissociation of the electron transport chain from ATP synthesis. Treatments with rotenone, dicoumarol, and oligomycin (i.e., oxidative phosphorylation inhibitors) decreased the survival rate of hydrated seeds under freezing conditions, which indicated that energy metabolism was related to the freezing tolerance of hydrated seeds. The predicted interactions between PN and MDM2-like proteins of Lactuca indicated that LsMDM2-5 forms two potential hydrogen bonds with PN. Furthermore, based on AlphaFold predictions and yeast 2-hybrid results, MDM2-5 might interact directly with NADH2. The knockdown of MDM2-5 by RNAi caused a higher level of NADH2 and ATPsyn and a higher freezing tolerance of hydrated seeds. This indicated that MDM2 played negative roles in regulating ATP synthesis and freezing tolerance of hydrated seeds.
A conceptual framework, called Innovation of Health Technology Assessment Methods (IHTAM), has been developed to facilitate the understanding of how to innovate methods of health technology assessment (HTA). However, the framework applicability has not been evaluated in practice. Hence, we aimed to explore framework applicability in three cases of method innovation that are part of the HTx project and to develop a roadmap to improve framework applicability.
Methods
The IHTAM framework was applied to three cases of innovating HTA methods. We collected feedback from case study leaders and consortium members after a training session, an approximately 1-year follow-up of periodic case study meetings, and a general assembly meeting where innovation progresses of the three cases were reported through surveys and interviews. Feedback was then summarized using an open-coding technique.
Results
According to feedback, the framework provided a structured way of deliberation and helped to improve collaboration among HTA stakeholders. However, framework applicability could be improved if it was complemented by a roadmap with a loop structure to provide tailored guidance for different cases, and with items to elaborate actions to be taken by stakeholders. Accordingly, a 48-item roadmap was developed.
Conclusions
The IHTAM framework was generally applicable to the three case studies. A roadmap, with loop structure and actionable items, could complement the framework, and may provide HTA stakeholders with tailored guidance on developing new methods. To further examine the framework applicability, we recommend stakeholders to apply the IHTAM framework and its roadmap in future practice.
This study presents observations of coherent modes (CMs) in a spherical tokamak using a microwave interferometer near the midplane. The CMs within the 30–60 kHz frequency range were observed during electron cyclotron resonance heating only, and the frequency of the CMs increased proportionally with the square root of the electron temperature near $R = 0.7m$. Generally, these modes displayed bursting and chirping signatures with strong density rise and fall. Their appearance indicated an increase in the intensity of hard x rays, suggesting a deterioration in energetic electron confinement. Furthermore, the effect of CMs on the intensity of energetic electron-driven whistler waves was observed. They decreased when CMs were present and gradually increased with the decrease in CM intensity. The CMs may influence the intensity of whistler waves by affecting the energetic electron confinement.
Certain rhythmic arterial pressure waves in humans and animals have been noticed for over one century. We found the novel and slowest arterial pressure waves in children following surgical repair for CHD, and examined their characteristics and clinical implications.
Methods:
We enrolled 212 children with 22 types of CHD within postoperative 48 h. We monitored haemodynamics (blood pressure, cardiac cycle efficiency, dP/dTmax), cerebral (ScO2), and renal (SrO2) oxygen saturation every 6 s. Electroencephalogram was continuously monitored. Mean blood flow velocity (Vm) of the middle cerebral artery was measured at 24 h.
Results:
We found the waves with a frequency of ∼ 90 s immediately following surgical repair in 46 patients in 12 types of CHD (21.7%), being most prevalent in patients with aortic arch abnormalities (Aorta Group, n = 24, 42.3%) or ventricular septal defect (Ventricular Septal Defect Group, n = 12, 23.5%). In Aorta and Ventricular Septal Defect Groups, the occurrence of the waves was associated with lower blood pressures, dP/dTmax, cardiac cycle efficiency, ScO2, SrO2, Vm, worse electroencephalogram background abnormalities, higher number of electroencephalogram sharp waves, and serum lactate (Ps <0.0001–0.07), and were accompanied with fluctuations of ScO2 and SrO2 in 80.6% and 69.6% of patients, respectively.
Conclusions:
The waves observed in children following cardiovascular surgery are the slowest ever reported, occurring most frequently in patients with aortic arch abnormalities or ventricular septal defect. While the occurrence of the waves was associated with statistically worse and fluctuated ScO2 and SrO2, worse systemic haemodynamics, and electroencephalogram abnormalities, at present these waves have no known clinical relevance.
This study closely replicates the analyses of the third research question in Römer and Berger (2019), which reported that the associations between verbs and verb argument constructions (VACs) used by German and Spanish learners of English move closer to a native usage norm as the learners’ proficiency increases. This study conducted the same correlation analyses from the original study but with a substantially expanded version of the learner corpus used therein. Additionally, we conducted zero-inflated negative binomial analyses to estimate the relationship between the frequencies of verb-VAC combinations in the British National Corpus (BNC) and in the learner subcorpora representing different proficiency levels. Our findings were consistent with the original study in showing significant positive correlations between frequencies of the verb-VAC combinations in the BNC and in the learner subcorpora but further revealed the potential effect of topic on the learners’ VAC usage. Implications for future studies are discussed.
Mild cognitive deficits (MCD) emerge before the first episode of psychosis (FEP) and persist in the clinical high-risk (CHR) stage. This study aims to refine risk prediction by developing MCD models optimized for specific early psychosis stages and target populations.
Methods
A comprehensive neuropsychological battery assessed 1059 individuals with FEP, 794 CHR, and 774 matched healthy controls (HCs). CHR subjects, followed up for 2 years, were categorized into converters (CHR-C) and non-converters (CHR-NC). The MATRICS Consensus Cognitive Battery standardized neurocognitive tests were employed.
Results
Both the CHR and FEP groups exhibited significantly poorer performance compared to the HC group across all neurocognitive tests (all p < 0.001). The CHR-C group demonstrated poorer performance compared to the CHR-NC group on three sub-tests: visuospatial memory (p < 0.001), mazes (p = 0.005), and symbol coding (p = 0.023) tests. Upon adjusting for sex and age, the performance of the MCD model was excellent in differentiating FEP from HC, as evidenced by an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.895 (p < 0.001). However, when applied in the CHR group for predicting CHR-C (AUC = 0.581, p = 0.008), the performance was not satisfactory. To optimize the efficiency of psychotic risk assessment, three distinct MCD models were developed to distinguish FEP from HC, predict CHR-C from CHR-NC, and identify CHR from HC, achieving accuracies of 89.3%, 65.6%, and 80.2%, respectively.
Conclusions
The MCD exhibits variations in domains, patterns, and weights across different stages of early psychosis and diverse target populations. Emphasizing precise risk assessment, our findings highlight the importance of tailored MCD models for different stages and risk levels.
The laboratory generation and diagnosis of uniform near-critical-density (NCD) plasmas play critical roles in various studies and applications, such as fusion science, high energy density physics, astrophysics as well as relativistic electron beam generation. Here we successfully generated the quasistatic NCD plasma sample by heating a low-density tri-cellulose acetate (TCA) foam with the high-power-laser-driven hohlraum radiation. The temperature of the hohlraum is determined to be 20 eV by analyzing the spectra obtained with the transmission grating spectrometer. The single-order diffraction grating was employed to eliminate the high-order disturbance. The temperature of the heated foam is determined to be T = 16.8 ± 1.1 eV by analyzing the high-resolution spectra obtained with a flat-field grating spectrometer. The electron density of the heated foam is about under the reasonable assumption of constant mass density.
This study presents novel findings on stochastic electron heating via a random electron cyclotron wave (ECW) in a spherical tokamak. Hard x ray measurements demonstrate the time evolution of hard x ray counts at different energy bands, consistent with predictions from the stochastic heating model. The ECW heating rate shows a positive correlation with applied power, confirming the effectiveness of stochastic heating. Remarkably, the ECW-driven plasma current remains insensitive to ECW incidence angle, consistent with model predictions. The observed stochastic heating of electrons offers potential for exploring innovative non-inductive current drive modes in spherical tokamaks. This research contributes to the understanding of plasma behaviour and motivates the development of new models for non-inductive current drive in fusion devices.
Palmitoyl-protein thioesterase (PPT), involved in the fatty acid synthesis and the de-palmitoylation of protein, was induced under ecological cooling treatment in hydrated lettuce seeds. However, there was no significant difference in fatty acid levels between the control and the cooled samples. To further study the function of PPT, 2-bromopalmitic acid (2-Bp), an inhibitor of protein palmitoylation, was applied during the imbibition of hydrated lettuce seeds, which was followed by slow-cooling treatment (−3°C h−1). The application of 2-Bp (1 mM) significantly increased the survival rate of seeds from 6.70% (control imbibition) to 22.67% (2-Bp imbibition) after slow cooling to −20°C. Differential scanning calorimetry (DSC) analysis indicated that 2-Bp led to earlier onset of ice crystals in the endosperm than the control group. Two-dimensional electrophoresis (2D) confirmed that 2-Bp could promote the hydrolysis of seed globulins and the accumulation of globulin peptides with small molecular weights. High-efficiency hydrolysis of globulin induced by mercaptoethanol improved the freezing tolerance of hydrated lettuce seeds and led to the accumulation of small globulin peptides, which further proved the positive function of small globulin polypeptides in enhancing the freezing tolerance of hydrated lettuce seeds. DSC of small globulin peptides showed that the smaller the molecular weight, the earlier the appearance of ice crystals and the higher the enthalpy of heat release. For the smallest peptides, the 2-Bp-4 in 2-Bp group exhibited higher enthalpy in exothermic peak than the control group (c-4). In conclusion, the hydrolysis of seed globulins and accumulation of small-molecule globulin peptides could be the major reason for improving the freezing tolerance of hydrated seeds after de-palmitoylation treatment.
This study aimed to articulate the roles of social support and coping strategies in the relation between childhood maltreatment (CM) and subsequent major depressive disorder (MDD) with a comprehensive exploration of potential factors in a longitudinal community-based cohort. Parallel and serial mediation analyses were applied to estimate the direct effect (DE) (from CM to MDD) and indirect effects (from CM to MDD through social support and coping strategies, simultaneously and sequentially). Sociodemographic characteristics and genetic predispositions of MDD were considered in the modeling process. A total of 902 participants were included in the analyses. CM was significantly associated with MDD (DE coefficient (β) = 0.015, 95% confidence interval (CI) = 0.002∼0.028). This relation was partially mediated by social support (indirect β = 0.004, 95% CI = 0.0001∼0.008) and negative coping (indirect β = 0.013, 95% CI = 0.008∼0.020), respectively. Social support, positive coping, and negative coping also influenced each other and collectively mediated the association between CM and MDD. This study provides robust evidence that although CM has a detrimental effect on later-on MDD, social support and coping strategies could be viable solutions to minimize the risk of MDD. Intervention and prevention programs should primarily focus on weakening negative coping strategies, then strengthening social support and positive coping strategies.
Sleep disturbance is an important factor in the pathophysiology and progression of psychiatric disorders, but whether it is a cause, or a downstream effect is still not clear.
Methods
To investigate causal relationships between three sleep-associated traits and seven psychiatric diseases, we used genetic variants related to insomnia, chronotype and sleep duration to perform a two-sample bidirectional Mendelian randomisation analysis. Summary-level data on psychiatric disorders were extracted from the Psychiatric Genomics Consortium. Effect estimates were obtained by using the inverse-variance-weighted (IVW), weights modified IVW, weighted-median methods, MR-Egger regression, MR pleiotropy residual sum and outlier (MR-PRESSO) test and Robust Adjusted Profile Score (RAPS).
Results
The causal odds ratio (OR) estimate of genetically determined insomnia was 1.33 (95% confidence interval (CI) 1.22–1.45; p = 5.03 × 10−11) for attention-deficit/hyperactivity disorder (ADHD), 1.31 (95% CI 1.25–1.37; p = 6.88 × 10−31) for major depressive disorder (MDD) and 1.32 (95% CI 1.23–1.40; p = 1.42 × 10−16) for post-traumatic stress disorder (PTSD). There were suggestive inverse associations of morningness chronotype with risk of MDD and schizophrenia (SCZ). Genetically predicted sleep duration was also nominally associated with the risk of bipolar disorder (BD). Conversely, PTSD and MDD were associated with an increased risk of insomnia (OR = 1.06, 95% CI 1.03–1.10, p = 7.85 × 10−4 for PTSD; OR = 1.37, 95% CI 1.14–1.64; p = 0.001 for MDD). A suggestive inverse association of ADHD and MDD with sleep duration was also observed.
Conclusions
Our findings provide evidence of potential causal relationships between sleep disturbance and psychiatric disorders. This suggests that abnormal sleep patterns may serve as markers for psychiatric disorders and offer opportunities for prevention and management in psychiatric disorders.
To understand the characteristics and influencing factors related to cluster infections in Jiangsu Province, China, we investigated case reports to explore transmission dynamics and influencing factors of scales of cluster infection. The effectiveness of interventions was assessed by changes in the time-dependent reproductive number (Rt). From 25th January to 29th February, Jiangsu Province reported a total of 134 clusters involving 617 cases. Household clusters accounted for 79.85% of the total. The time interval from onset to report of index cases was 8 days, which was longer than that of secondary cases (4 days) (χ2 = 22.763, P < 0.001) and had a relationship with the number of secondary cases (the correlation coefficient (r) = 0.193, P = 0.040). The average interval from onset to report was different between family cluster cases (4 days) and community cluster cases (7 days) (χ2 = 28.072, P < 0.001). The average time interval from onset to isolation of patients with secondary infection (5 days) was longer than that of patients without secondary infection (3 days) (F = 9.761, P = 0.002). Asymptomatic patients and non-familial clusters had impacts on the size of the clusters. The average reduction in the Rt value in family clusters (26.00%, 0.26 ± 0.22) was lower than that in other clusters (37.00%, 0.37 ± 0.26) (F = 4.400, P = 0.039). Early detection of asymptomatic patients and early reports of non-family clusters can effectively weaken cluster infections.
Major depressive disorder (MDD) is a common debilitating disorder characterized by impaired spontaneous brain activity, yet little is known about its alterations in dynamic properties and the molecular mechanisms associated with these changes.
Methods
Based on the resting-state functional MRI data of 65 first-episode, treatment-naïve patients with MDD and 66 healthy controls, we compared dynamic regional homogeneity (dReHo) of spontaneous brain activity between the two groups, and we investigated gene expression profiles associated with dReHo alterations in MDD by leveraging transcriptional data from the Allen Human Brain Atlas and weighted gene co-expression network analysis.
Results
Compared with healthy controls, patients with MDD consistently showed reduced dReHo in both fusiform gyri and in the right temporal pole and hippocampus. The expression profiles of 16 gene modules were correlated with dReHo alterations in MDD. These gene modules were enriched for various biological process terms, including immune, synaptic signalling, ion channels, mitochondrial function and protein metabolism, and were preferentially expressed in different cell types.
Conclusions
Patients with MDD have reduced dReHo in brain areas associated with emotional and cognitive regulation, and these changes may be related to complex polygenetic and polypathway mechanisms.
We closely replicated Wu and Ortega (2013), who found that an elicited imitation test (EIT) reliably distinguished low-level from high-level language abilities among instructed second language (L2) learners of Mandarin Chinese. The original study sampled learners (1) from second-level courses to represent low-level language abilities and (2) from third-, fourth- and graduate-level courses to represent high-level language abilities. Results showed high-level learners outperformed low-level learners on the Mandarin EIT. Our close replication used Wu and Ortega's (2013) materials and procedures in order to understand (1) the extent to which this EIT can additionally distinguish between finer-grained language abilities and (2) the ways in which the broad grouping of language abilities in the high group may have contributed to the findings. Sixty-five instructed L2 learners from four instructional levels were assigned to one of three groups: Beginner (first-level courses), Low (second-level courses), High (third- and fourth-level courses). Consistent with the original study, our results showed clear between-group differences, indicating that the EIT can distinguish between both broad (beginner vs high) and finer-grained (beginner vs low, low vs high) language abilities. These results are discussed in light of the original study's findings with implications for proficiency assessment in second language acquisition (SLA) research.
Influenza activity is subject to environmental factors. Accurate forecasting of influenza epidemics would permit timely and effective implementation of public health interventions, but it remains challenging. In this study, we aimed to develop random forest (RF) regression models including meterological factors to predict seasonal influenza activity in Jiangsu provine, China. Coefficient of determination (R2) and mean absolute percentage error (MAPE) were employed to evaluate the models' performance. Three RF models with optimum parameters were constructed to predict influenza like illness (ILI) activity, influenza A and B (Flu-A and Flu-B) positive rates in Jiangsu. The models for Flu-B and ILI presented excellent performance with MAPEs <10%. The predicted values of the Flu-A model also matched the real trend very well, although its MAPE reached to 19.49% in the test set. The lagged dependent variables were vital predictors in each model. Seasonality was more pronounced in the models for ILI and Flu-A. The modification effects of the meteorological factors and their lagged terms on the prediction accuracy differed across the three models, while temperature always played an important role. Notably, atmospheric pressure made a major contribution to ILI and Flu-B forecasting. In brief, RF models performed well in influenza activity prediction. Impacts of meteorological factors on the predictive models for influenza activity are type-specific.
This study aim to derive and validate a simple and well-performing risk calculator (RC) for predicting psychosis in individual patients at clinical high risk (CHR).
Methods
From the ongoing ShangHai-At-Risk-for-Psychosis (SHARP) program, 417 CHR cases were identified based on the Structured Interview for Prodromal Symptoms (SIPS), of whom 349 had at least 1-year follow-up assessment. Of these 349 cases, 83 converted to psychosis. Logistic regression was used to build a multivariate model to predict conversion. The area under the receiver operating characteristic (ROC) curve (AUC) was used to test the effectiveness of the SIPS-RC. Second, an independent sample of 100 CHR subjects was recruited based on an identical baseline and follow-up procedures to validate the performance of the SIPS-RC.
Results
Four predictors (each based on a subset of SIPS-based items) were used to construct the SIPS-RC: (1) functional decline; (2) positive symptoms (unusual thoughts, suspiciousness); (3) negative symptoms (social anhedonia, expression of emotion, ideational richness); and (4) general symptoms (dysphoric mood). The SIPS-RC showed moderate discrimination of subsequent transition to psychosis with an AUC of 0.744 (p < 0.001). A risk estimate of 25% or higher had around 75% accuracy for predicting psychosis. The personalized risk generated by the SIPS-RC provided a solid estimate of conversion outcomes in the independent validation sample, with an AUC of 0.804 [95% confidence interval (CI) 0.662–0.951].
Conclusion
The SIPS-RC, which is simple and easy to use, can perform in the same manner as the NAPLS-2 RC in the Chinese clinical population. Such a tool may be used by clinicians to counsel appropriately their patients about clinical monitor v. potential treatment options.
Heat-resistant Al–8.5Fe–1.3V–1.7Si (wt%) aluminum alloy components were fabricated using selective laser melting (SLM). The as-built samples were examined in terms of density, chemical composition, surface morphologies, microstructures, and mechanical behavior. The results show that nearly full dense samples with the relative density of 99.3% can be produced. The chemical composition of the deposited material is close to that of the powder, presenting a limited aluminum loss and a low oxygen pickup. The SLM specimens consist of three typical zones: the fusion zone (FZ), the remelting border zone (RBZ), and the heat-affected zone (HAZ). Ultrafine continuous cellular α-Al networks are observed in the FZ. The HAZ exhibits fine rounded Al12(Fe,V)3Si particles (10–70 nm) distributed homogeneously in the α-Al matrix, while the rectangle-like AlmFe-type phase (m = 4.0–4.4) with 100–500 nm in size is preferably formed in the RBZ. The microhardness of the parts shows directional independent, with a mean value of 246 HV0.1.
Skeletal muscle is a major site for the oxidation of fatty acids (FA) in mammals, including humans. Using a swine model, we tested the hypothesis that dietary protein intake regulates the expression of key genes for lipid metabolism in skeletal muscle. A total of ninety-six barrows (forty-eight pure-bred Bama mini-pigs (fatty genotype) and forty-eight Landrace pigs (lean genotype)) were fed from 5 weeks of age to market weight. Pigs of fatty or lean genotype were randomly assigned to one of two dietary treatments (low- or adequate-protein diet), with twenty-four individually fed pigs per treatment. Our data showed that dietary protein levels affected the expression of genes involved in the anabolism and catabolism of lipids in the longissimus dorsi and biceps femoris muscles in a genotype-dependent manner. Specifically, Bama mini-pigs had more intramuscular fat, SFA and MUFA, as well as elevated mRNA expression levels of lipogenic genes, compared with Landrace pigs. In contrast, Bama mini-pigs had lower mRNA expression levels of lipolytic genes than Landrace pigs fed an adequate-protein diet in the growing phase. These data are consistent with higher white-fat deposition in Bama mini-pigs than in Landrace pigs. In conclusion, adequate provision of dietary protein (amino acids) plays an important role in regulating the expression of key lipogenic genes, and the growth of white adipose tissue, in a genotype- and tissue-specific manner. These findings have important implications for developing novel dietary strategies in pig production.
Objective: Previous studies indicated that the levels of serum interleukin (IL)-12 at baseline were elevated in obsessive-compulsive disorder (OCD) patients compared with control subjects, suggesting that IL-12 maybe involved in the etiopathogenesis of OCD. Therefore, we study the relationship between 1188A/C polymorphism of IL-12(rs3212227) and OCD in Chinese Han population.
Methods: We genotyped 194 OCD patients and 322 healthy individuals by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), then analyzed the data using case-control association test.
Results: No significant differences were found in 1188A/C genotypic and allelic frequencies between OCD cases and controls (X2 = 2.12, df = 2, P = 0.35 by genotype; X2 = 0.005, df = 1, P = 0.94 by allele).
Conclusions: Our results suggested that there may be lack of an association between OCD and IL-12 1188A/C polymorphism in Chinese Han population.