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Previous studies have reported comorbidities of autoimmune thyroid disorders (AITD), including Hashimoto’s disease (HT) and Graves’ disease (GD), and celiac disease (CeD), as well as the possible beneficial effects of a gluten-free diet (GFD) on AITD. Nonetheless, it remains uncertain whether there is a genetic causal relationship between AITD and CeD, while the beneficial effects on a GFD are controversial. This study aim to explore the causal relationship between CeD and AITD, particularly with HT, and to determine whether a GFD is beneficial for AITD. We performed a two-sample Mendelian Randomization (MR) analysis on data from the largest meta-analysis summary statistics of AITD, CeD and GFD. Genetic instrumental variables were established by pinpointing single nucleotide polymorphisms (SNPs) that relate to corresponding factors. In assessing sensitivity and heterogeneity, we conducted examinations of MR Egger, weighted median, simple mode, weighted mode, and MR Egger intercept tests. HT was found to play a pathogenic role in increasing the risk of CeD (ORIVW = 1.544 [95%CI 1.153-2.068], p = 0.00355), and our Mendelian randomization study does not support genetic liability related to CeD with GD (Graves’ disease) and GFD with AITD. This study supports the positive correlation between HT risk and CeD risk, while GFD has no protective effect on AITD and may exert its effect through other mechanisms. These findings provide valuable insights into potential targets for disease intervention and treatment at the genetic level.
Internet addiction (IA) refers to excessive internet use that causes cognitive impairment or distress. Understanding the neurophysiological mechanisms underpinning IA is crucial for enabling an accurate diagnosis and informing treatment and prevention strategies. Despite the recent increase in studies examining the neurophysiological traits of IA, their findings often vary. To enhance the accuracy of identifying key neurophysiological characteristics of IA, this study used the phase lag index (PLI) and weighted PLI (WPLI) methods, which minimize volume conduction effects, to analyze the resting-state electroencephalography (EEG) functional connectivity. We further evaluated the reliability of the identified features for IA classification using various machine learning methods.
Methods
Ninety-two participants (42 with IA and 50 healthy controls (HCs)) were included. PLI and WPLI values for each participant were computed, and values exhibiting significant differences between the two groups were selected as features for the subsequent classification task.
Results
Support vector machine (SVM) achieved an 83% accuracy rate using PLI features and an improved 86% accuracy rate using WPLI features. t-test results showed analogous topographical patterns for both the WPLI and PLI. Numerous connections were identified within the delta and gamma frequency bands that exhibited significant differences between the two groups, with the IA group manifesting an elevated level of phase synchronization.
Conclusions
Functional connectivity analysis and machine learning algorithms can jointly distinguish participants with IA from HCs based on EEG data. PLI and WPLI have substantial potential as biomarkers for identifying the neurophysiological traits of IA.
Upper extremity rehabilitation robots have become crucial in stroke rehabilitation due to their high durability, repeatability, and task-specific capabilities. A significant challenge in assessing the comfort performance of these robots is accurately calculating the human-robot interaction forces. In this study, a four-degree-of-freedom (4-DOF) upper extremity rehabilitation robot mechanism, kinematically compatible with the human upper limb, is proposed. Based on this mechanism, an algorithm for estimating human-robot interaction forces is developed using Newton-Euler dynamics. A prototype of the proposed robot is constructed, and a series of comparative experiments are carried out to validate the feasibility of the proposed force estimation approach. The results indicate that the proposed method reliably predicts interaction forces with minimal deviation from experimental data, demonstrating its potential for application in upper limb rehabilitation robots. This work provides a foundation for future studies focused on comfort evaluation and optimization of rehabilitation robots, with significant practical implications for improving patient rehabilitation outcomes.
Broadband frequency-tripling pulses with high energy are attractive for scientific research, such as inertial confinement fusion, but are difficult to scale up. Third-harmonic generation via nonlinear frequency conversion, however, remains a trade-off between bandwidth and conversion efficiency. Based on gradient deuterium deuterated potassium dihydrogen phosphate (KDxH2-xPO4, DKDP) crystal, here we report the generation of frequency-tripling pulses by rapid adiabatic passage with a low-coherence laser driver facility. The efficiency dependence on the phase-matching angle in a Type-II configuration is studied. We attained an output at 352 nm with a bandwidth of 4.4 THz and an efficiency of 36%. These results, to the best of our knowledge, represent the first experimental demonstration of gradient deuterium DKDP crystal in obtaining frequency-tripling pulses. Our research paves a new way for developing high-efficiency, large-bandwidth frequency-tripling technology.
We aimed to examine the association between dietary Se intake and CVD risk in Chinese adults.
Design:
This prospective cohort study included adults above 20 years old in the China Health and Nutrition Survey (CHNS), and they were followed up from 1997 to 2015 (n 16 030). Dietary data were retrieved from CHNS, and a 3-d, 24-h recall of food intake was used to assess the cumulative average intake of dietary Se, which was divided into quartiles. The Cox proportional hazards model was adopted to analyse the association between dietary Se intake and incident CVD risk.
A total of 663 respondents developed CVD after being followed up for a mean of 9·9 years (median 9 years). The incidence of CVD was 4·3, 3·7, 4·6 and 4·0 per 1000 person-years across the quartiles of cumulative Se intake. After adjusting all potential factors, no significant associations were found between cumulative Se intake and CVD risk. No interactions were found between Se intake and income, urbanisation, sex, region, weight, hypertension and CVD risk.
Conclusion:
We found no association between dietary Se and CVD.
Young children today are exposed to masks on a regular basis. However, there is limited empirical evidence on how masks may affect word learning. The study explored the effect of masks on infants’ abilities to fast-map and generalize new words. Seventy-two Chinese infants (43 males, Mage = 18.26 months) were taught two novel word-object pairs by a speaker with or without a mask. They then heard the words and had to visually identify the correct objects and also generalize words to a different speaker and objects from the same category. Eye-tracking results indicate that infants looked longer at the target regardless of whether a speaker wore a mask. They also looked longer at the speaker’s eyes than at the mouth only when words were taught through a mask. Thus, fast-mapping and generalization occur in both masked and not masked conditions as infants can flexibly access different visual cues during word-learning.
To identify risk genes whose expression are regulated by the reported risk variants and to explore the potential regulatory mechanism in schizophrenia (SCZ).
Methods
We systematically integrated three independent brain expression quantitative traits (eQTLs) (CommonMind, GTEx, and BrainSeq Phase 2, a total of 1039 individuals) and GWAS data (56 418 cases and 78 818 controls), with the use of transcriptome-wide association study (TWAS). Diffusion magnetic resonance imaging was utilized to quantify the integrity of white matter bundles and determine whether polygenic risk of novel genes linked to brain structure was present in patients with first-episode antipsychotic SCZ.
Results
TWAS showed that eight risk genes (CORO7, DDAH2, DDHD2, ELAC2, GLT8D1, PCDHA8, THOC7, and TYW5) reached transcriptome-wide significance (TWS) level. These findings were confirmed by an independent integrative approach (i.e. Sherlock). We further conducted conditional analyses and identified the potential risk genes that driven the TWAS association signal in each locus. Gene expression analysis showed that several TWS genes (including CORO7, DDAH2, DDHD2, ELAC2, GLT8D1, THOC7 and TYW5) were dysregulated in the dorsolateral prefrontal cortex of SCZ cases compared with controls. TWS genes were mainly expressed on the surface of glutamatergic neurons, GABAergic neurons, and microglia. Finally, SCZ cases had a substantially greater TWS genes-based polygenic risk (PRS) compared to controls, and we showed that fractional anisotropy of the cingulum-hippocampus mediates the influence of TWS genes PRS on SCZ.
Conclusions
Our findings identified novel SCZ risk genes and highlighted the importance of the TWS genes in frontal-limbic dysfunctions in SCZ, indicating possible therapeutic targets.
The mitochondrial genome provides important information for phylogenetic analysis and an understanding of evolutionary origin. In this study, the mitochondrial genomes of Ilisha elongata and Setipinna tenuifilis were sequenced, which are typical circular vertebrate mitochondrial genomes composed of 16,770 and 16,805 bp, respectively. The mitogenomes of I. elongata and S. tenuifilis include 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA), two ribosomal RNA (rRNA) genes and one control region (CR). Both two species' genome compositions were highly A + T biased and exhibited positive AT-skews and negative GC-skews. The genetic distance and Ka/Ks ratio analyses indicated that 13 PCGs were affected by purifying selection and the selection pressures were different from certain deep-sea fishes, which were most likely due to the difference in their living environment. Results of phylogenetic analysis support close relationships among Chirocentridae, Denticipitidae, Clupeidae, Engraulidae and Pristigasteridae based on the nucleotide and amino acid sequences of 13 PCGs. Within Clupeoidei, I. elongata and S. tenuifilis were most closely related to the family Pristigasteridae and Engraulidae, respectively. These results will help to better understand the evolutionary position of Clupeiformes and provide a reference for further phylogenetic research on Clupeiformes species.
O’Grady’s generalised Franchetta conjecture (GFC) is concerned with codimension 2 algebraic cycles on universal polarised K3 surfaces. In [4], this conjecture has been studied in the Betti cohomology groups. Following a suggestion of Voisin, we investigate this problem in the Deligne-Beilinson (DB) cohomology groups. In this paper, we develop the theory of Deligne-Beilinson cohomology groups on (smooth) Deligne-Mumford stacks. Using the automorphic cohomology group and Noether-Lefschetz theory, we compute the 4th DB-cohomology group of universal oriented polarised K3 surfaces with at worst an $A_1$-singularity and show that GFC for such family holds in DB-cohomology. In particular, this confirms O’Grady’s original conjecture in DB cohomology.
Understanding the patterns of treatment response is critical for the treatment of patients with schizophrenia; one way to achieve this is through using a longitudinal dynamic process study design.
Aims
This study aims to explore the response trajectory of antipsychotics and compare the treatment responses of seven different antipsychotics over 6 weeks in patients with schizoprenia (trial registration: Chinese Clinical Trials Registry Identifier: ChiCTR-TRC-10000934).
Method
Data were collected from a multicentre, randomised open-label clinical trial. Patients were evaluated with the Positive and Negative Syndrome Scale (PANSS) at baseline and follow-up at weeks 2, 4 and 6. Trajectory groups were classified by the method of k-means cluster modelling for longitudinal data. Trajectory analyses were also employed for the seven antipsychotic groups.
Results
The early treatment response trajectories were classified into a high-trajectory group of better responders and a low-trajectory group of worse responders. The results of trajectory analysis showed differences compared with the classification method characterised by a 50% reduction in PANSS scores at week 6. A total of 349 patients were inconsistently grouped by the two methods, with a significant difference in the composition ratio of treatment response groups using these two methods (χ2 = 43.37, P < 0.001). There was no differential contribution of high- and low trajectories to different drugs (χ2 = 12.52, P = 0.051); olanzapine and risperidone, which had a larger proportion in the >50% reduction at week 6, performed better than aripiprazole, quetiapine, ziprasidone and perphenazine.
Conclusions
The trajectory analysis of treatment response to schizophrenia revealed two distinct trajectories. Comparing the treatment responses to different antipsychotics through longitudinal analysis may offer a new perspective for evaluating antipsychotics.
Witherite originates from the biochemical sedimentation of barium in sea water. Due to the complexity of the metallogenic environment, witherite appears in many morphologies. However, the relationship between its diverse morphologies and its mineralisation environment is not well understood. In this paper, Ca2+, a common substitute for Ba2+, and mixed protein (egg white) were used to simulate the inorganic and organic environments of witherite mineralisation, respectively. Comparison of samples prepared under different conditions showed that Ca2+ and egg white have relatively independent regulatory effects on the mineralisation of witherite particles. Egg white primarily limits the growth of the nanocrystals, while Ca2+ directs their non-isodiametric growth. Results shows that Ca2+ is distributed along a gradient in nanocrystalline witherite particles, with the Ca2+ content being proportional to the diameter of the nanocrystals. The results of this study shed light on the different roles of organic matter and inorganic ions in the formation of witherite and offer insight into the genesis of its various morphologies.
Activated carbon (AC) has been widely used as catalyst for oxygen reduction reaction (ORR) in air-cathode microbial fuel cells (MFCs). Here we demonstrate a new method to improve the AC air-cathode by blending it with reduced graphene oxide (rGO). rGO sheets are first deposited on Ni foam and AC is then brushed onto it with controlled mass loading. rGO sheets not only improve the electrical conductivity of AC, but also provide a large number of ORR areas. Rotating ring disk electrode measurements reveal that the number of transferred electrons at rGO-AC cathode is 3.5, indicating the four-electron pathway is the dominant process. Significantly, the MFC with rGO-AC cathode delivers a maximum power density of 2.25 ± 0.05 W/m2, which is substantially higher than that of plain AC cathode (1.35 ± 0.07 W/m2) and those for other air-cathode MFCs using AC as ORR catalyst under the same mass loading.
Small, irregular terraces on hillslopes, or terracettes, are common landscape features throughout west central China. Despite their prevalence, there is limited understanding of the nature of these topographic features, the processes that form them, and the role humans played in their formation. We used an interdisciplinary approach to investigate the geology, ecology, and cultural history of terracette development within Jiuzhaigou National Park, Sichuan Province, China. Terracettes occur on south facing, 20° slopes at 2500 m elevation, which appears to coincide with places people historically preferred to build villages. Ethnographic interviews suggest that traditional swidden agricultural cycles removed tree roots, causing the loess sediments to lose cohesion, slump, and the terrace risers to retreat uphill over time. This evidence is supported by landslide debris at terracette faces. Archaeological analysis of terracette sites reveal remains of rammed spread soil structures, bones, stone tools, and ceramics dating from at least 2200 years before present within a distinct paleosol layer. Radiocarbon and optically stimulated luminescence dating of terracette sediments ranged in age from between 1500 and 2000 14C yr BP and between 16 and 0.30"ka, respectively. These multiple lines of evidence indicate a long history of human habitation within Jiuzhaigou National Park and taken together, suggest strong links between terracette formation and human-landuse interactions.
The therapeutic effect of mesenchymal stem cells (MSCs) has been investigated in various clinical applications, in which their functional benefits are mainly attributed to the secretion of soluble factors. The enhancement of their therapeutic potential by physical and chemical properties of cell culture substrate is a safe and effective strategy, since they are highly sensitive to their microenvironment such as the elasticity and surface topography. In this study, we demonstrated that the geometry of polymeric substrate regulated the interleukin-6 (IL-6) secretion of human adipose derived MSCs. Polystyrene substrates comprising arrays of square-shaped (S50) or round-shaped (R50) microwells (side length or diameter of 50 μm and depth of 10 μm) were prepared by injection molding. Cellular apoptototic rate of MSCs was not affected by the microwell geometry, while the upregulated secretion of IL-6 and the enhancement of nuclear transcription factor STAT3 were detected in MSCs seeded on S50 substrate. The geometry-dependent modulatory effect was highly associated with ROCK signaling cascade. The inhibition of ROCK abolished the disparity in IL-6 secretion. These findings highlight the possibility to steer the secretion profile of stem cells via microwell geometry in combination with the manipulation of ROCK signaling pathway.
Schistosoma japonicum, a human blood fluke, causes a parasitic disease affecting millions of people in Asia. Thioredoxin–glutathione system of S. japonicum plays a critical role in maintaining the redox balance in parasite, which is a potential target for development of novel antischistosomal agents. Here we cloned the gene of S. japonicum thioredoxin (SjTrx), expressed and purified the recombinant SjTrx in Escherichia coli. Functional assay shows that SjTrx catalyses the dithiothreitol (DTT) reduction of insulin disulphide bonds. The coupling assay of SjTrx with its endogenous reductase, thioredoxin glutathione reductase from S. japonicum (SjTGR), supports its biological function to maintain the redox homeostasis in the cell. Furthermore, the crystal structure of SjTrx in the oxidized state was determined at 2·0 Å resolution, revealing a typical architecture of thioredoxin fold. The structural information of SjTrx provides us important clues for understanding the maintenance function of redox homeostasis in S. japonicum and pathogenesis of this chronic disease.