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CD33 has been implicated in the pathogenesis of Alzheimer’s disease primarily through its role in inhibiting the clearance of beta-amyloid (Aβ). However, genetic studies yield mixed results and it is unclear whether the impact of CD33 is specific to Alzheimer’s disease or related to broader neurodegenerative processes. Interestingly, CD33 has also been shown to interact with the hepatitis B (HBV) and C viruses (HCV).
Aims
This study aims to investigate the effects of CD33 single-nucleotide polymorphisms (SNPs) on cognitive functions across diverse populations, including healthy controls, individuals with chronic HBV or HCV and those diagnosed with Parkinson’s disease.
Method
We genotyped CD33 SNPs in 563 participants using the Affymetrix platform. Participants’ cognitive functions were cross-sectionally assessed using a neuropsychological test battery spanning six domains.
Results
Our analysis revealed that CD33 SNP variations had no significant cognitive impact on healthy individuals or Parkinson’s disease patients. However, chronic HBV and HCV patients exhibited significant cognitive differences, particularly in memory, related to CD33 SNP genotypes. Moderation analysis indicated a heightened influence of CD33 SNPs on cognitive functions in chronic HBV and HCV individuals. Our data also suggest that inflammation severity may modulate the cognitive effects in hepatitis patients with specific CD33 SNPs.
Conclusions
This study highlights the importance of CD33 SNPs in cognitive outcomes, emphasising their role in the context of chronic viral hepatitis. It contributes to understanding the cognitive profiles influenced by CD33 SNPs and posits CD33’s potential contribution to neurodegenerative disease progression, potentially intensified by HBV/HCV-induced inflammation.
Immunological castration can be an alternative to traditional surgical castration. The active immunization against GnRH or kisspeptin has a castrating effect. To date, the fusion protein vaccine of combination with GnRH and kisspeptin have not been studied. Thus, the present study will develop a GnRH6-kisspeptin vaccine by genetic engineering method and investigate its immunocastration effect in male rats. Twenty 20-day-old male rats were randomly divided into two groups: the control group (n=10) and the immunization group (n=10). The initial immunization took place at week 0 followed by three booster doses administered intervals. The control group received an equivalent dose of white oil adjuvant. Orbital blood samples were collected at various time points following the initial immunization, at 0, 2, 4, 6, 8, 10 and 12 weeks, respectively. The entire left testis was weighed and its volume measured at week 12. Samples from the right testis were obtained for histological analysis. Serum levels of GnRH and kisspeptin antibodies, as well as testosterone levels were determined using ELISA. The results showed that the serum levels of GnRH and kisspeptin antibody titres of the immunized rats were significantly higher compared to the control group (P<0.05). Additionally, the testosterone concentration was effectively reduced following the intensified immunization. The testes of the immunized group exhibited a reduction in size and a significant decrease in the number of spermatogonia in the testicular tissue compared to the control group (P<0.05). These data indicate that the recombinant GnRH6-kisspeptin protein effectively induced immunological castration in rats.
The betatron radiation source features a micrometer-scale source size, a femtosecond-scale pulse duration, milliradian-level divergence angles and a broad spectrum exceeding tens of keV. It is conducive to the high-contrast imaging of minute structures and for investigating interdisciplinary ultrafast processes. In this study, we present a betatron X-ray source derived from a high-charge, high-energy electron beam through a laser wakefield accelerator driven by the 1 PW/0.1 Hz laser system at the Shanghai Superintense Ultrafast Laser Facility (SULF). The critical energy of the betatron X-ray source is 22 ± 5 keV. The maximum X-ray flux reaches up to 4 × 109 photons for each shot in the spectral range of 5–30 keV. Correspondingly, the experiment demonstrates a peak brightness of 1.0 × 1023 photons·s−1·mm−2·mrad−2·0.1%BW−1, comparable to those demonstrated by third-generation synchrotron light sources. In addition, the imaging capability of the betatron X-ray source is validated. This study lays the foundation for future imaging applications.
Studying the effect of interleukin-17 (IL-17) on the mechanism of CD4+ T-cell immune regulation and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway may offer new ideas and methods for the therapy of dilated cardiomyopathy.
Methods:
Naive CD4+ T cells were isolated from mice using a magnetic bead sorting reagent and manipulated by overexpression or knockdown of IL-17. Protein levels of Janus kinase 2 (JAK2), phosphorylated JAK2 (p-JAK2), signal transducer and activator of transcription 3 (STAT3), phosphorylated STAT3 (p-STAT3), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9) were determined by Western blotting. Quantitative polymerase chain reaction was used to assess the levels of JAK2, STAT3, MMP-2, and MMP-9. Expression of tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-4 (IL-4), and interferon-gamma (IFNγ) was determined by enzyme-linked immunosorbent assay test kits. TNF-α, IL-1β, IL-4, and IFNγ secretion was measured by flow cytometry.
Results:
In CD4+ T cells, IL-17 overexpression increased TNF-α, IL-1β, IL-4, IFNγ, p-JAK2, p-STAT3, MMP-2, MMP-9 levels, and apoptosis. Knockdown of IL-17 reduced the levels of TNF-α, IL-1β, IL-4, IFNγ, p-JAK2, p-STAT3, MMP-2, and MMP-9, as well as the level of apoptosis.
Conclusion:
Through regulation of IL-17 expression in CD4+ T cells, this study reveals its crucial role in regulating the secretion of inflammatory factors, activation of the JAK/STAT signaling pathway, expression of matrix metalloproteinases, and apoptosis of CD4+ T cells.
The material removal rate (MRR) serves as a crucial indicator in the chemical mechanical polishing (CMP) process of semiconductor wafers. Currently, the mainstream method to ascertain the MRR through offline measurements proves time inefficient and struggles to represent process variability accurately. An efficient MRR prediction model based on stacking ensemble learning that integrates models with disparate architectures was proposed in this study. First, the processing signals collected during wafer polishing, as available in the PHM2016 dataset, were analyzed and preprocessed to extract statistical and neighbor domain features. Subsequently, Pearson correlation coefficient analysis (PCCA) and principal component analysis (PCA) were employed to fuse the extracted features. Ultimately, random forest (RF), light gradient boosting machine (LightGBM), and backpropagation neural network (BPNN) with hyperparameters optimized by the Bayesian Optimization Algorithm were integrated to establish an MRR prediction model based on stacking ensemble learning. The developed model was verified on the PHM2016 benchmark test set, and a Mean Square Error (MSE) of 7.72 and a coefficient of determination (R2) of 95.82% were achieved. This indicates that the stacking ensemble learning based model, integrated with base models of disparate architectures, offers considerable potential for real-time MRR prediction in the CMP process of semiconductor wafers.
Choline and betaine are important in the body, from cell membrane components to methyl donors. We aimed to investigate trends in dietary intake and food sources of total choline, individual choline forms and betaine in Chinese adults using data from the China Health and Nutrition Survey (CHNS) 1991–2011, a prospective cohort with a multistage, random cluster design. Dietary intake was estimated using three consecutive 24-h dietary recalls in combination with a household food inventory. Linear mixed-effect models were constructed using R software. A total of 11 188 men and 12 279 women aged 18 years or older were included. Between 1991 and 2011, total choline intake increased from 219·3 (95 % CI 215·1, 223·4) mg/d to 269·0 (95 % CI 265·6, 272·5) mg/d in men and from 195·6 (95 % CI 191·8, 199·4) mg/d to 240·4 (95 % CI 237·4, 243·5) mg/d in women (both P-trends < 0·001). Phosphatidylcholine was the major form of dietary choline, and its contribution to total choline increased from 46·9 % in 1991 to 58·8 % in 2011. Cereals were the primary food source of total choline before 2000, while eggs had ranked at the top since 2004. Dietary betaine intake was relatively steady over time with a range of 134·0–151·5 mg/d in men (P-trend < 0·001) and 111·7–125·3 mg/d in women (P-trend > 0·05). Chinese adults experienced a significant increase in dietary intake of choline, particularly phosphatidylcholine during 1991–2011 and animal-derived foods have replaced plant-based foods as the main food sources of choline. Betaine intake remained relatively stable over time. Future efforts should address the health effects of these changes.
The aim of this 4-year follow-up study was to examine the predictive effects of demographics, three types of sexual stigma, three types of self-identity confusion, anxiety, depression, family support and problematic Internet use before the coronavirus disease 2019 (COVID-19) pandemic on new-onset suicide risk and persistent suicide risk in young adult lesbian, gay and bisexual individuals who experienced the COVID-19 pandemic in Taiwan.
Methods
Baseline data were collected from 1,000 lesbian, gay and bisexual individuals in 2018 and 2019. Outcome data on suicide risk were collected again in 2023. The suicide module of the Mini International Neuropsychiatric Interview was used to assess suicide risk in terms of thoughts of death, desire to self-harm, thoughts of suicide, plans for suicide and suicide attempts in the preceding month at the initial and follow-up assessments. Baseline three types of sexual stigma, self-identity disturbance, depression, anxiety and problematic Internet use were used to examine their prediction of new-onset suicide risk and persistent suicide risk at follow-up.
Results
In total, 673 individuals participated in the follow-up survey. Notably, 16.5% of the participants who had no suicide risk at baseline had new-onset suicide risk at follow-up; 46.4% of the participants who had suicide risk at baseline also had suicide risk at follow-up. Participants who were transgender (p = .003), who perceived greater levels of microaggression (p < .001), and who had greater levels of problematic Internet use at baseline (p = .024) were more likely to have new-onset suicide risk at follow-up. Participants who had greater levels of self-identity confusion were more likely to have persistent suicide risk at follow-up (p = .023).
Conclusion
Intervention strategies for reducing suicide risk in lesbian, gay and bisexual individuals should be developed with consideration of the predictors identified in this study.
Dietary n-3 PUFA may have potential benefits in preventing peptic ulcer disease (PUD). However, data from observational epidemiological studies are limited. Thus, we conducted a Mendelian randomisation analysis to reveal the causal impact of n-3 PUFA on PUD. Genetic variants strongly associated with plasma levels of total or individual n-3 PUFA including plant-derived α-linolenic acid and marine-derived EPA, DPA and DHA were enrolled as instrumental variables. Effect size estimates of the n-3 PUFA-associated genetic variants with PUD were evaluated using data from the UK biobank. Per one sd increase in the level of total n-3 PUFA in plasma was significantly associated with a lower risk of PUD (OR = 0·91; 95 % CI 0·85, 0·99; P = 0·020). The OR were 0·81 (95 % CI 0·67, 0·97) for EPA, 0·72 (95 % CI 0·58, 0·91) for DPA and 0·87 (95 % CI 0·80, 0·94) for DHA. Genetically predicted α-linolenic acid levels in plasma had no significant association with the risk of PUD (OR = 5·41; 95 % CI 0·70, 41·7). Genetically predicted plasma levels of n-3 PUFA were inversely associated with the risk of PUD, especially marine-based n-3 PUFA. Such findings may have offered an effective and feasible strategy for the primary prevention of PUD.
Numerical simulations are carried out on the vortex-induced rotations of a freely rotatable rigid square cylinder in a two-dimensional uniform cross-flow. A range of Reynolds numbers between 40 and 150 and density ratios between 0.1 and 10 are considered. Results show eight different characteristic regimes, expanding the classification of Ryu & Iaccarino (J. Fluid Mech., vol. 813, 2017, pp. 482–507). New regimes include the transition and wavy rotation regimes; in the ${\rm \pi}$-limited oscillation regime we observe multipeak subregimes. Moment-generating mechanisms of these regimes and subregimes are further elucidated. A phenomenon related to the influence of density ratio is the tooth-like shape of the ${\rm \pi} /2$-limit oscillation regime observed in the regime map, which is explained as a result of the imbalance relation between the main frequencies of rotation response and the vortex shedding frequency. In addition, existence of multiple regimes and multistable states are discussed, indicating multiple stable attractive structures in phase space.
Various psychosocial and psychological interventions have been developed to reduce schizophrenia relapse prevention. A better understanding of these active interventions is important for clinical practice and for meaningful allocation of resources. However, no bibliometric analysis of this area has been conducted. Studies were retrieved from the Web of Science Core Collection database. The publication outputs and cooperation of institutions were visualized with Origin 2021. Global cooperation was visualized using ArcGIS Pro3.0. VOSviewer was used to generate visualizations of network of authors and keywords. The number of annual publications generally showed a fluctuating upward trend over the past 20 years. Germany published the most relevant articles (361, 26.76%). The Technical University of Munich was the most productive institution (70, 9.86%). Leucht Stefan published the most articles (46, 6.48%) and had the highest number of citations (4,375 citations). Schizophrenia Research published the most studies (39, 5.49%). Keywords were roughly classified into three clusters: cognitive behavioral therapy (CBT), family interventions and family psychoeducation and other factors related to interventions. The findings provided the current status of research on psychosocial and psychological interventions for schizophrenia relapse prevention from a bibliometric perspective. Recent research has mainly focused on CBT, family interventions and family psychoeducation.
In order to establish a compact all-optical Thomson scattering source, experimental studies were conducted on the 45 TW Ti: sapphire laser facility. By including a steel wafer, mixed gas, and plasma mirror into a double-exit jet, several mechanisms, such as shock-assisted ionization injection, ionization injection, and driving laser reflection, were integrated into one source. So, the source of complexity was remarkably reduced. Electron bunches with central energy fluctuating from 90 to 160 MeV can be produced. Plasma mirrors were used to reflect the driving laser. The scattering of the reflected laser on the electron bunches led to the generation of X-ray photons. Through comparing the X-ray spots under different experimental conditions, it is confirmed that the X-ray photons are generated by Thomson scattering. For further application, the energy spectra and source size of the Thomson scattering source were measured. The unfolded spectrum contains a large amount of low-energy photons besides a peak near 67 keV. Through importing the electron energy spectrum into the Monte Carlo simulation code, the different contributions of the photons with small and large emitting angles can be used to explain the origin of the unfolded spectrum. The maximum photon energy extended to about 500 keV. The total photon production was 107/pulse. The FWHM source size was about 12 μm.
The objective of this study was to understand and measure epigenetic changes associated with the occurrence of CHDs by utilizing the discordant monozygotic twin model. A unique set of monozygotic twins discordant for double-outlet right ventricles (DORVs) was used for this multiomics study. The cardiac and muscle tissue samples from the twins were subjected to whole genome sequencing, whole genome bisulfite sequencing, RNA-sequencing and liquid chromatography-tandem mass spectrometry analysis. Sporadic DORV cases and control fetuses were used for validation. Global hypomethylation status was observed in heart tissue samples from the affected twins. Among 36,228 differentially methylated regions (DMRs), 1097 DMRs involving 1039 genes were located in promoter regions. A total of 419 genes, and lncRNA–mRNA pairs involved 30 genes, and 62 proteins were significantly differentially expressed. Multiple omics integrative analysis revealed that five genes, including BGN, COL1A1, COL3A1, FBLN5, and FLAN, and three pathways, including ECM-receptor interaction, focal adhesion and TGF-β signaling pathway, exhibited differences at all three levels. This study demonstrates a multiomics profile of discordant twins and explores the possible mechanism of DORV development. Global hypomethylation might be associated with the risk of CHDs. Specific genes and specific pathways, particularly those involving ECM–receptor interaction, focal adhesion and TGF–β signaling, might be involved in the occurrence of CHDs.
Data on trends in the epidemiological burden of bipolar disorder are scarce.
Aims
To provide an overview of trends in bipolar disorder burden from 1990 to 2019.
Method
Revisiting the Global Burden of Disease Study 2019, we analysed the number of cases, calculated the age-standardised rate (per 100 000 population) and estimated annual percentage change (EAPC) of incidence, prevalence and years lived with disability (YLDs) for bipolar disorder from 1990 to 2019. The independent effects of age, period and cohort were estimated by the age–period–cohort modelling.
Results
Globally, the bipolar disorder-related prevalent cases, incident cases and number of YLDs all increased from 1990 to 2019. Regionally, the World Health Organization Region of the Americas accounted for the highest estimated YLD number and rate, with the highest age-standardised prevalence rate in 1990 and 2019 and highest EAPC of prevalence. By sociodemographic index (SDI) quintiles, all five SDI regions saw an increase in estimated incident cases. Nationally, New Zealand reported the highest age-standardised rate of incidence, prevalence and YLDs in 1990 and 2019. The most prominent age effect on incidence rate was in those aged 15–19 years. Decreased effects of period on incidence, prevalence and YLD rates was observed overall and in females, not in males. The incidence, prevalence and YLD rates showed an unfavourable trend in the younger cohorts born after 1990, with males reporting a higher cohort risk than females.
Conclusions
From 1990 to 2019, the overall trend of bipolar disorder burden presents regional and national variations and differs by age, sex, period and cohort.
There is growing evidence that gray matter atrophy is constrained by normal brain network (or connectome) architecture in neuropsychiatric disorders. However, whether this finding holds true in individuals with depression remains unknown. In this study, we aimed to investigate the association between gray matter atrophy and normal connectome architecture at individual level in depression.
Methods
In this study, 297 patients with depression and 256 healthy controls (HCs) from two independent Chinese dataset were included: a discovery dataset (105 never-treated first-episode patients and matched 130 HCs) and a replication dataset (106 patients and matched 126 HCs). For each patient, individualized regional atrophy was assessed using normative model and brain regions whose structural connectome profiles in HCs most resembled the atrophy patterns were identified as putative epicenters using a backfoward stepwise regression analysis.
Results
In general, the structural connectome architecture of the identified disease epicenters significantly explained 44% (±16%) variance of gray matter atrophy. While patients with depression demonstrated tremendous interindividual variations in the number and distribution of disease epicenters, several disease epicenters with higher participation coefficient than randomly selected regions, including the hippocampus, thalamus, and medial frontal gyrus were significantly shared by depression. Other brain regions with strong structural connections to the disease epicenters exhibited greater vulnerability. In addition, the association between connectome and gray matter atrophy uncovered two distinct subgroups with different ages of onset.
Conclusions
These results suggest that gray matter atrophy is constrained by structural brain connectome and elucidate the possible pathological progression in depression.
Longitudinal studies on the variations of phenotypic and genotypic characteristics of K. pneumoniae across two decades are rare. We aimed to determine the antimicrobial susceptibility and virulence factors for K. pneumoniae isolated from patients with bacteraemia or urinary tract infection (UTI) from 1999 to 2022. A total of 699 and 1,267 K. pneumoniae isolates were isolated from bacteraemia and UTI patients, respectively, and their susceptibility to twenty antibiotics was determined; PCR was used to identify capsular serotypes and virulence-associated genes. K64 and K1 serotypes were most frequently observed in UTI and bacteraemia, respectively, with an increasing frequency of K20, K47, and K64 observed in recent years. entB and wabG predominated across all isolates and serotypes; the least frequent virulence gene was htrA. Most isolates were susceptible to carbapenems, amikacin, tigecycline, and colistin, with the exception of K20, K47, and K64 where resistance was widespread. The highest average number of virulence genes was observed in K1, followed by K2, K20, and K5 isolates, which suggest their contribution to the high virulence of K1. In conclusion, we found that the distribution of antimicrobial susceptibility, virulence gene profiles, and capsular types of K. pneumoniae over two decades were associated with their clinical source.
Rodents and shrews are major reservoirs of various pathogens that are related to zoonotic infectious diseases. The purpose of this study was to investigate co-infections of zoonotic pathogens in rodents and shrews trapped in four provinces of China. We sampled different rodent and shrew communities within and around human settlements in four provinces of China and characterised several important zoonotic viral, bacterial, and parasitic pathogens by PCR methods and phylogenetic analysis. A total of 864 rodents and shrews belonging to 24 and 13 species from RODENTIA and EULIPOTYPHLA orders were captured, respectively. For viral pathogens, two species of hantavirus (Hantaan orthohantavirus and Caobang orthohantavirus) were identified in 3.47% of rodents and shrews. The overall prevalence of Bartonella spp., Anaplasmataceae, Babesia spp., Leptospira spp., Spotted fever group Rickettsiae, Borrelia spp., and Coxiella burnetii were 31.25%, 8.91%, 4.17%, 3.94%, 3.59%, 3.47%, and 0.58%, respectively. Furthermore, the highest co-infection status of three pathogens was observed among Bartonella spp., Leptospira spp., and Anaplasmataceae with a co-infection rate of 0.46%. Our results suggested that species distribution and co-infections of zoonotic pathogens were prevalent in rodents and shrews, highlighting the necessity of active surveillance for zoonotic pathogens in wild mammals in wider regions.
Consumer misperception and misinterpretation of food labels can lead to consumers not buying a product or purchasing products that do not align with their environmental or sustainability interests. Consumer purchasing behavior can be explained by looking at consumer food values or food quality attributes. This study aimed to (a) determine the effect label information has on consumer preference shares for selected sustainability-related food labels and (b) if correlations exist between food labels and food values. To the best of our knowledge, this is the first study to examine the comprehension of 12 different labels and identify how food labels relate to food value preferences. Responses from the best-worst scaling experiment of food value and environmental food label choice sets were analyzed using the random parameter logit model. Results reveal preference shares changed for each label as more information was provided to the respondents about the various labels included in the study. These findings should support food policy efforts requiring strict, clear label standards. Food labels should represent the food’s core food values to increase consumer preference for the product. These findings also further support the need for efforts to increase consumer knowledge and understanding of the labels on food packaging.
When a droplet coalesces with a flat liquid–air interface, a secondary drop may be left behind resulting in only a partial coalescence rather than complete coalescence. In this paper, we employ an arbitrary Lagrangian–Eulerian method to demonstrate that applying an electric field favours the occurrence of partial coalescence. To understand this phenomenon, we systematically study the effect of an external electric field on the coalescence process between a droplet and a liquid–air interface. In an electric field, the induced electric stresses can overcome the downward flow of the droplet, thus lifting it upwards. As a result, the positive Laplace pressure in the neck region squeezes the droplet towards pinch-off. We observe that both the initial neck expansion and neck shrinkage are suppressed by the electric field. These effects become weaker as the Ohnesorge number $Oh$ increases. Based on the scaling analysis, we report a critical Ohnesorge number $O{h_c} = 14.39{\varGamma ^{3/2}} + 0.029$ to quantify the transition from partial coalescence to complete coalescence in the presence of an electric field, where $\varGamma $ represents the dimensionless electric Bond number. Finally, a relationship between the secondary droplet size and the two key dimensionless numbers of $Oh$ and $\varGamma $ has been developed, which could be useful for producing droplets of desired sizes in microfluidic applications.