The small heat shock protein Hsp20.8 imparts tolerance to high temperatures in the leafminer fly, Liriomyza trifolii (Diptera: Agtomyzidae).

As an environmental factor, temperature impacts the distribution of species and influences interspecific competition. The molecular chaperones encoded by small heat shock proteins (sHsps) are essential for rapid, appropriate responses to environmental stress. This study focuses on Hsp20.8, which encodes a temperature-responsive sHsp in Liriomyza trifolii, an insect pest that infests both agricultural and ornamental crops. Hsp20.8 expression was highest at 39℃ in L. trifolii pupae and adults, and expression levels were greater in pupae than in adults. Recombinant Hsp20.8 was expressed in Escherichia coli and conferred a higher survival rate than the empty vector to bacterial cells exposed to heat stress. RNA interference experiments were conducted using L. trifolii adults and prepupae and the knockdown of Hsp20.8 expression increased mortality in L. trifolii during heat stress. The results expand our understanding of sHsp function in Liriomyza spp. and the ongoing adaptation of this pest to climate change. In addition, this study is also important for predicting the distribution of invasive species and proposing new prevention and control strategies based on temperature adaptation.

Identification of Genetic Variants for Risk Prediction and Early Diagnosis of Age-Related Macular Degeneration in the Taiwanese Population.

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly worldwide. The prevalence and phenotypes of AMD differ among populations, including between people in Taiwan and other regions. We performed a genome-wide association study to identify genetic variants and to develop genetic models to predict the risk of AMD development and progression in the Taiwanese population. In total, 4039 patients with AMD and 16,488 non-AMD controls (aged ≥ 65 years) were included. We identified 31 AMD-associated variants (p < 5 × 10-8) on chromosome 10q26, surrounding PLEKHA1-ARMS2-HTRA1. Two genetic models were constructed using the clump and threshold method. Model 1 included the single nucleotide polymorphism rs11200630 and showed a 1.31-fold increase in the risk of AMD per risk allele (95% confidence interval (CI) = 1.20-1.43, p < 0.001). In model 2, 1412 single-nucleotide polymorphisms were selected to construct a polygenic risk score (PRS). Individuals with the top 5% PRS had a 1.40-fold higher AMD risk compared with that of individuals with a PRS in the bottom quartile (95% CI = 1.04-1.89, p = 0.025). Moreover, the PRS in the upper quartile was related to a decreased age at AMD diagnosis by 0.62 years (95% CI = -1.15, -0.09, p = 0.023). Both genetic models provide useful predictive power for populations at high risk of AMD, affording a basis for identifying patients requiring close follow-up and early intervention.

Impact of the trans-ancestry polygenic risk score on type 2 diabetes risk, onset age and progression among population in Taiwan.

Type 2 diabetes (T2D) prevalence in adults at a younger age has increased but the disease status may go unnoticed. This study aimed to determine whether the onset age and subsequent diabetic complications can be attributed to the polygenic architecture of T2D in the Taiwan Han population. A total of 9,627 cases with T2D and 85,606 controls from the Taiwan Biobank were enrolled. Three diabetic polygenic risk scores (PRSs), PRS_EAS and PRS_EUR, and a trans-ancestry PRS (PRS_META), calculated using summary statistic from East Asian and European populations. The onset age was identified by linking to the National Taiwan Insurance Research Database, and the incidence of different diabetic complications during follow-up was recorded. PRS_META (7.4%) explained a higher variation for T2D status. And the higher percentile of PRS is also correlated with higher percentage of T2D family history and prediabetes status. More, the PRS was negatively associated with onset age (ß = -0.91 yr), and this was more evident among males (ß = -1.11 vs. -0.76 for males and females, respectively). The hazard ratio of diabetic retinopathy (DR) and diabetic foot were significantly associated with PRS_EAS and PRS_META, respectively. However, the PRS was not associated with other diabetic complications, including diabetic nephropathy, cardiovascular disease, and hypertension. Our findings indicated that diabetic PRS which combined susceptibility variants from cross-population could be used as a tool for early screening of T2D, especially for high-risk populations, such as individuals with high genetic risk, and may be associated with the risk of complications in subjects with T2D. NEW & NOTEWORTHY Our findings indicated that diabetic polygenic risk score (PRS) which combined susceptibility variants from Asian and European population affect the onset age of type 2 diabetes (T2D) and could be used as a tool for early screening of T2D, especially for individuals with high genetic risk, and may be associated with the risk of diabetic complications among people in Taiwan.

Characterization of genes encoding heat shock proteins reveals a differential response to temperature in two geographic populations of Liriomyza trifolii (Diptera: Agromyzidae).

Liriomyza trifolii is a significant, invasive pest that damages horticultural crops and vegetables. The distribution of L. trifolii is influenced by temperature, and prior research has demonstrated that variations in thermal adaptability differ among geographic populations of the insect. Heat shock proteins (Hsps) are involved in adaptation to temperatures; however, the underlying molecular mechanism for thermal adaption in different L. trifolii populations remains unclear. This study examines the temperature adaptability of two L. trifolii populations from Hainan (HN) and Jiangsu (JS) provinces. The results indicate that the HN population has a higher survival rate and a higher critical thermal maximum (CTmax) than the JS population under high temperature stress. Transcriptome data at 42 °C revealed that the JS population has more differentially expressed genes (DEGs) than the HN population, while the HN population has more upregulated DEGs. The two populations were similar in functional annotation of DEGs, and a large number of Hsps were upregulated. However, the HN population had larger numbers and higher expression levels of Hsps during heat stress as compared to the JS population. Additionally, the expression patterns of differentially expressed Hsps varied between the HN and JS populations in response to different elevated temperatures. Notably, the transcription levels of Hsp70s were higher in the HN population as compared to the JS population, while the expression level of genes encoding small heat shock proteins was higher in the JS population. These findings have significant scientific value in understanding the underlying mechanism of temperature adaption in L. trifolii and provide a fresh perspective on the distribution of this invasive pest.

The development of abamectin resistance in Liriomyza trifolii and its contribution to thermotolerance.

BACKGROUND: Liriomyza trifolii is an economically significant, invasive pest of horticultural and vegetable crops. The larvae form tunnels in foliage and hasten senescence and death. Outbreaks of L. trifolii often erupt in hot weather and are driven by thermotolerance; furthermore, the poor effectiveness of pesticides has made outbreaks more severe. But it is still unclear whether the development of insecticide tolerance will contribute to thermotolerance in L. trifolii. RESULTS: To explore potential synergistic relationships between insecticide exposure and thermotolerance in L. trifolii, we first generated an abamectin-resistant (AB-R) strain. Knockdown behavior, eclosion and survival rates, and expression levels of genes encoding heat shock proteins (Hsps) in L. trifolii were then examined in AB-R and abamectin-susceptible (AB-S) strains. Our results demonstrated that long-term selection pressure for abamectin resistance made L. trifolii more prone to develop cross-resistance to other insecticides containing similar ingredients. Furthermore, the AB-R strain exhibited enhanced thermotolerance and possessed an elevated critical thermal maximum temperature, and upregulated expression levels of Hsps during heat stress. CONCLUSION: Collectively, our results indicate that thermal adaptation in L. trifolii was accompanied by emerging abamectin resistance. This study provides a theoretical basis for investigating the synergistic or cross-adaptive mechanisms that insects use to cope with adversity and demonstrates the complexity of insect adaptation to environmental and chemical stress. © 2023 Society of Chemical Industry.

Structure-based development of a canine TNF-α-specific antibody using adalimumab as a template.

The canine anti-tumor necrosis factor-alpha (TNF-α) monoclonal antibody is a potential therapeutic option for treating canine arthritis. The current treatments for arthritis in dogs have limitations due to side effects, emphasizing the need for safer and more effective therapies. The crystal structure of canine TNF-α (cTNF-α) was successfully determined at a resolution of 1.85 Å, and the protein was shown to assemble as a trimer, with high similarity to the functional quaternary structure of human TNF-α (hTNF-α). Adalimumab (Humira), a known TNF-α inhibitor, effectively targets and neutralizes TNF-α to reduce inflammation and has been used to manage autoimmune conditions such as rheumatoid arthritis. By comparing the structure of cTNF-α with the complex structure of hTNF-α and adalimumab-Fab, the epitope of adalimumab on cTNF-α was identified. The significant structural similarities of epitopes in cTNF-α and hTNF-α indicate the potential of using adalimumab to target cTNF-α. Therefore, a canine/human chimeric antibody, Humivet-R1, was created by grafting the variable domain of adalimumab onto a canine antibody framework derived from ranevetmab. Humivet-R1 exhibits potent neutralizing ability (IC50 = 0.05 nM) and high binding affinity (EC50 = 0.416 nM) to cTNF-α, comparable to that of adalimumab for both hTNF-α and cTNF-α. These results strongly suggest that Humivet-R1 has the potential to provide effective treatment for canine arthritis with reduced side effects. Here, we propose a structure-guided antibody design for the use of a chimeric antibody to treat canine inflammatory disease. Our successful development strategy can speed up therapeutic antibody discovery for animals and has the potential to revolutionize veterinary medicine.

Serving the Underserved? Uptake, Effectiveness, and Acceptability of Digital SSIs for Rural American Adolescents.

OBJECTIVE: Rural teens are less likely to access care for depression than urban teens. Evidence-based digital single-session interventions (SSIs), offered via social media advertisements, may be well suited to narrowing this gap in treatment access and increasing access to support for adolescents living in rural areas. We evaluated the viability of using social media-based advertisements to equitably recruit adolescents living in rural areas with elevated depression symptoms to digital SSIs; we sought to characterize and assess whether SSI completion rates and acceptability differed for adolescents living in rural versus more urban areas, across three intervention conditions (two active, evidence-based SSIs; one placebo control); and we tested whether digital SSIs differentially reduced depressive symptoms. METHOD: We used pre-intervention and three-month follow up data from 13- to 16-year-old adolescents (N = 2,322; 88% female; 55% non-Hispanic White) within a web-based randomized control trial of three free, digital SSIs (ClinicalTrials.gov identifier: NCT04634903) collected eight months into the COVID-19 pandemic in the United States. RESULTS: Digital SSIs reached adolescents at population-congruent rates; however, social media ads resulted in relative underrepresentation of youths from rural areas who hold minoritized racial/ethnic identities. Adolescents living in rural areas also completed digital SSIs at similar rates to their urban peers, found SSIs equivalently as acceptable, and reported comparable depression symptom reductions as youth living in urban areas. CONCLUSION: Digital SSIs and their dissemination through social media may offer a promising means of narrowing the gap between access to evidence-based mental health support between adolescents living in rural and urban areas; however, targeted efforts are warranted to reach racially minoritized youths in rural U.S. counties.

Childhood trauma is associated with early-onset but not late-onset suicidal behavior in late-life depression.

OBJECTIVES: To examine the relationship between childhood traumatic experiences and early and late-onset suicidal behavior among depressed older adults. DESIGN: Cross-sectional study. SETTING: Inpatient and outpatient psychiatric services in Pennsylvania. PARTICIPANTS: Our sample included 224 adults aged 50+ (M ± SD = 62.5 ± 7.4) recruited into three depressed groups: (1) 84 suicide attempters, (2) 44 suicide ideators, and (3) 58 non-suicidal comparisons, and a non-psychiatric healthy comparison group (N = 38). MEASUREMENTS: The Childhood Trauma Questionnaire measured experiences of childhood trauma such as emotional abuse, physical abuse, emotional neglect, physical neglect, and sexual abuse. RESULTS: Attempters were separated into early- and late-onset based on age of first attempt using a statistical algorithm that identified a cutoff age of 30 years old. Overall, we found group differences in emotional and physical abuse and neglect in both genders and sexual abuse in females, but not in males. Early-onset attempters experienced more childhood emotional abuse and neglect than late-onset attempters and were more likely to have experienced multiple forms of abuse. They also experienced more emotional abuse and neglect than all comparison groups. Consistently, early-onset attempters more often met criteria for current or lifetime PTSD relative to late-onset attempters and most comparison groups. Late-onset attempters had similar levels of childhood trauma as other depressed groups. CONCLUSIONS: Our study reaffirms that there are distinct pathways to suicidal behavior in older adults based on their age of first suicide attempt and that trauma experienced in childhood has long-lasting emotional and behavioral consequences, even into late life.

Combining polygenic risk scores and human leukocyte antigen variants for personalized risk assessment of type 1 diabetes in the Taiwanese population.

AIMS: To analyse the genome-wide association study (GWAS) data of patients with type 1 diabetes mellitus (T1D) in order to develop a risk score for the genetic effects on T1D risk and age at diagnosis in the Taiwanese population. MATERIALS AND METHODS: We selected 610 patients with T1D and 2511 healthy individuals from an electronic medical record database of more than 300 000 individuals with genetic information, analysed their GWAS data, and developed a polygenic risk score (PRS). RESULTS: The PRS, based on 149 selected single-nucleotide polymorphisms, could effectively predict T1D risk. A PRS increase was associated with increased T1D risk (odds ratio [OR] 2.09, 95% confidence interval [CI] 1.72-2.55). Moreover, a 1-unit increase in standardized T1D PRS decreased the age at diagnosis by 0.74 years. Combined PRS and human leukocyte antigen (HLA) DQA1*03:02-DQA1*05:01 genotypes could accurately predict T1D risk. In multivariable models, HLA variants and PRS were independent risk factors for T1D risk (OR 3.76 [95% CI 1.54-9.16] and 1.71 [95% CI 1.37-2.13] for HLA DQA1*03:02-DQA1*05:01 and PRS, respectively). In a limited study population of those aged ≤18 years, PRS remained significantly associated with T1D risk. The association between T1D PRS and age at diagnosis was more obvious among males and patients aged ≤18 years. CONCLUSIONS: Polygenic risk score and HLA variations enable personalized risk estimates, enhance newborn screening efficiency for ketoacidosis prevention, and addresses the gap in data on T1D prediction in isolated Asian populations.

Long-Term Suicidal Ideation Profiles in Late-Life Depression and Their Association With Suicide Attempt or Death by Suicide.

Objective: In young and middle-aged adults, suicidal ideation is an important predictor of prospective suicide attempts, but its predictive power in late life remains unclear. In this study, we used Latent Profile Analysis (LPA) in a cohort of depressed older adults to identify distinct ideation profiles and their clinical correlates and test their association with risk of suicidal behavior longitudinally.Methods: A total of 337 depressed older adults (aged 50-93 years) were assessed for suicidal ideation and behavior for up to 14 years (median = 3 years), at least once per year (study period: 2002-2020). LPA was used, which derived 4 profiles of ideation scores based on subject-level aggregates. Groups were compared using analysis of variance (ANOVA) and χ2 tests at baseline and competing risk survival analysis during follow-up.Results: Ideation showed significant decline over time, on average (P < .001). LPA identified 4 suicidal ideation profiles. Risk of suicide attempt/death was higher for chronic severe ideators (age-adjusted hazard ratio [HR] = 5.75; 95% CI, 2.25-14.7; P < .001) and highly variable ideators (HR = 3.21; 95% CI, 1.03-10.1; P = .045) compared to fast-remitting ideators, despite comparable current ideation severity at baseline. Fast-remitting ideators had higher risk than low/non-ideators with no attempts or suicides (P < .001). Chronic severe ideators displayed the most severe dysfunction across personality, social characteristics, and impulsivity measures, whereas highly variable and fast-remitting ideators displayed specific deficits.Conclusions: Assessing suicidal ideation over months/years has clinical relevance, as it enabled the identification of distinct ideation patterns associated with substantive differences in clinical presentation and risk of future suicidal behavior despite similar ideation levels at baseline.

Mechanistic effects of microwave radiation on pupal emergence in the leafminer fly, Liriomyza trifolii.

Liriomyza trifolii is a significant pest of vegetable and ornamental crops across the globe. Microwave radiation has been used for controlling pests in stored products; however, there are few reports on the use of microwaves for eradicating agricultural pests such as L. trifolii, and its effects on pests at the molecular level is unclear. In this study, we show that microwave radiation inhibited the emergence of L. trifolii pupae. Transcriptomic studies of L. trifolii indicated significant enrichment of differentially expressed genes (DEGs) in 'post-translational modification, protein turnover, chaperones', 'sensory perception of pain/transcription repressor complex/zinc ion binding' and 'insulin signaling pathway' when analyzed with the Clusters of Orthologous Groups, Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes databases, respectively. The top DEGs were related to reproduction, immunity and development and were significantly expressed after microwave radiation. Interestingly, there was no significant difference in the expression of genes encoding heat shock proteins or antioxidant enzymes in L. trifolii treated with microwave radiation as compared to the untreated control. The expression of DEGs encoding cuticular protein and protein takeout were silenced by RNA interference, and the results showed that knockdown of these two DEGs reduced the survival of L. trifolii exposed to microwave radiation. The results of this study help elucidate the molecular response of L. trifolii exposed to microwave radiation and provide novel ideas for control.

Insect hormones affect the toxicity of the insecticidal growth regulator cyromazine in Liriomyza trifolii (Diptera: Agromyzidae).

The leafminer Liriomyza trifolii is an important insect pest of ornamental and vegetable crops worldwide. Cyromazine is an effective, commonly-used insecticide that functions as a growth regulator, but its effect on L. trifolii has not been previously reported. In this study, transcriptome analysis was undertaken in L. trifolii exposed to cyromazine. Clusters of orthologous groups analysis indicated that a large number of differentially expressed genes responding to cyromazine were categorized as "lipid transport and metabolism", "post-translational modification, protein turnover, chaperones", and "cell wall/membrane/envelope biogenesis". Gene ontology analysis indicated that pathways associated with insect hormones, growth and development, and cuticle synthesis were significantly enriched. In general, the transcriptome results showed that the genes related to insect hormones were significantly expressed after treatment with cyromazine. Furthermore, the combined exposure of L. trifolii to cyromazine and the hormone analogues 20-hydroxyecdysone (20E) or juvenile hormone (JH) indicated that hormone analogues can change the expression pattern of hormone-related genes (20EP and JHEH) and pupal length. The combined application of cyromazine with 20E improved the survival rate of L. trifolii, whereas the combination of JH and cyromazine reduced survival. The results of this study help elucidate the mechanistic basis for cyromazine toxicity and provide a foundation for understanding cyromazine resistance.

Comparative transcriptome analysis of Liriomyza trifolii (Burgess) and Liriomyza sativae (Blanchard) (Diptera: Agromyzidae) in response to rapid cold hardening.

The ability of insets to react efficiently to fluctuation in temperature is crucial for them to survive in variable surroundings. Rapid cold hardening (RCH) is a process that increase cold tolerance in most insect species. The molecular mechanisms of RCH remain largely unknown, and whether it is associated with transcriptional changes is unclear. In this study, we compared the transcriptomes of Liriomyza trifolii and L. sativae exposed to RCH to investigate the transcript abundance due to RCH in both species. RNA-seq revealed 93,166 assembled unigenes, and 34,303 of these were annotated in the L. trifolii and L. sativae transcriptome libraries. After a 4-h treatment at 1°C (RCH) compared with control, 268 and 606 unigenes were differentially expressed in L. trifolii and L. sativae, respectively. When comparing pupae exposed to 2h cold shock directly with pupae went through 4h acclimation prior to 2h cold shock, 60 and 399 unigenes were differentially expressed in L trifolii and L sativae, respectively. Genes that were commonly expressed in both L. trifolii and L. sativae, included cytochrome P450, cuticular protein, glucose dehydrogenase, solute carrier family 22 and cationic amino acid transporter. Additionally, several pathways including galactose metabolism and peroxisome were significantly enriched during RCH. Our results show that the transcriptional response is correlated with RCH in the pupal stage of the two Liriomyza species, but more transcriptional changes were identified in L sativae than in L. trifolii.

RNA Interference of Chitin Synthase 2 Gene in Liriomyza trifolii through Immersion in Double-Stranded RNA.

Liriomyza trifolii is an important invasive pest that infects horticultural vegetables, displaying a strong competitive advantage and showing great potential for inflicting harm. Chitin synthase is one of the key enzymes in insect chitin metabolism and plays an important role in insect growth and development. In this study, a chitin synthase (CHS) transcript of L. trifolii was cloned, and the results showed that LtCHS belongs to the CHS2 family. The expression analysis indicated the presence of the highest abundance of LtCHS2 in the pupae at different developmental stages but showed no significant difference among different tissues in the adult. Furthermore, a dsRNA immersion method was developed for RNA interference (RNAi) in L. trifolii using LtCHS2 transcript. RNAi can significantly reduce the expression of LtCHS2 in pupae, and the emergence rate of the pupae was significantly lower than that of the control. The results provide a theoretical basis for exploring the role of chitin synthase gene in L. trifolii and proposing new pest control strategies.

Transcriptome analysis and screening of putative sex-determining genes in the invasive pest, Frankliniella occidentalis (Thysanoptera: Thripidae).

The invasive insect pest, Frankliniella occidentalis, is a well-known vector that transmits a variety of ornamental and vegetable viruses. The mechanistic basis of sex determination in F. occidentalis is not well understood, and this hinders our ability to deploy sterile insect technology as an integrated pest management strategy. In this study, six cDNA libraries from female and male adults of F. occidentalis (three biological replicates each) were constructed and transcriptomes were sequenced. A total of 6000 differentially-expressed genes were identified in the two sexes including 2355 up- and 3645 down-regulated genes. A total of 149 sex-related genes were identified based on GO enrichment data and included transformer-2 (tra2), fruitless (fru), male-specific lethal (msl) and sex lethal (sxl); several of these exhibited sex-specific and/or sex-biased expression in F. occidentalis. This study contributes to our understanding of the sex-determined cascade in F. occidentalis and other members of the Thysanoptera.

Identification, expression analysis and functional verification of two genes encoding small heat shock proteins in the western flower thrips, Frankliniella occidentalis (Pergande).

Small heat shock proteins (sHSPs) help prevent the irreversible aggregation of denatured proteins that occurs in response to organismal stress. In this study, we identified two intron-free genes encoding sHSPs from Frankliniella occidentalis; these were designated FoHSP11.6 and FoHSP28.0 and belonged to an atypical and typical sHSP family, respectively. Both FoHSPs were transcribed in all developmental stages of F. occidentalis with the highest expression levels in pupae and adults and greater expression in males than females. Although the FoHSPs had different temperature-induced expression profiles, they were generally induced by both low and high temperatures and reached maximal expression levels after 0.5-1 h of temperature stress. The FoHSPs expression levels in pupae were induced by drought and high humidity, and higher expression levels were correlated with lower survival rates. The thermotolerance of F. occidentalis decreased when theFoHSPs were silenced by RNA interference. Our results show that FoHSP11.6 and FoHSP28.0 are involved in the response to temperature and drought and may also function in growth and development of F. occidentalis.

Species Identity Dominates over Environment in Driving Bacterial Community Assembly in Wild Invasive Leaf Miners.

The microbiota of invasive animal species may be pivotal to their adaptation and spread, yet the processes driving the assembly and potential sources of host-microbiota remain poorly understood. Here, we characterized microbiota of four Liriomyza leaf miner fly species totaling 310 individuals across 43 geographical populations in China and assessed whether the microbiota of the wild leaf miner was acquired from the soil microbiota or the host plant microbiota, using high-throughput 16S rRNA sequencing. Bacterial communities differed significantly among four leaf miner species but did not mirror host phylogeny. Microbiota diversity in the native L. chinensis was significantly higher than in three invasive leaf miners (i.e., L. trifolii, L. huidobrensis, and L. sativae), yet the microbial community of the invasive species exhibited a more connected and complex network structure. Structural equation models revealed that host species identity was more important than environmental factors (e.g., geography, climate, or plants) in shaping microbiota composition. Using neutral and null model analyses, we found that deterministic processes like variable selection played a primary role in driving microbial community assembly, with some influence by stochastic processes like drift. The relative degree of these processes governing microbiota was likely correlated with host species but independent of either geographical or climatic factors. Finally, source tracking analysis showed that leaf miners might acquire microbes from their host plant rather than the soil. Our results provide a robust assessment of the ecological processes governing bacterial community assembly and potential sources of microbes in invasive leaf miners. IMPORTANCE The invasion of foreign species, including leaf miners, is a major threat to world biota. Host-associated microbiota may facilitate host adaption and expansion in a variety of ways. Thus, understanding the processes that drive leaf miner microbiota assembly is imperative for better management of invasive species. However, how microbial communities assemble during the leaf miner invasions and how predictable the processes remain unexplored. This work quantitatively deciphers the relative importance of deterministic process and stochastic process in governing the assembly of four leaf miner microbiotas and identifies potential sources of leaf miner-colonizing microbes from the soil-plant-leaf miner continuum. Our study provides new insights into the mechanisms underlying the drive of leaf miner microbiota assembly.

Efficacy of a Smartphone Application to Promote Maternal Influenza Vaccination: A Randomized Controlled Trial.

The maternal vaccine coverage rate has been low in Taiwan. We developed an "Influenza Vaccination Reminder Application" and evaluated its efficacy in improving vaccination intention among pregnant women in Taiwan. A randomized controlled trial was conducted to compare the positive change in vaccination intention between the experimental group and the control group. Pregnant women who were more than 20 years old and at less than 32 weeks of gestation were recruited from four regional hospitals in southern Taiwan during November 2020 to April 2021. Pregnant women were randomly assigned to the experimental group, to whom the "Influenza Vaccination Reminder Application" was provided for at least two months, while pregnant women in the control group received regular maternal education only. The differences in knowledge about influenza and its vaccines, attitudes towards maternal influenza vaccination, and behavior intention of influenza vaccination among pregnant women before and after the experiment intervention were compared between two groups. The results included 126 women in the experimental group and 117 women in the control group and showed that the "Influenza Vaccination Reminder Application" increased pregnant women's knowledge about influenza and vaccines (percentage increase in the experimental group and control group: 11.64% vs. 7.39%), strengthened their positive attitudes towards maternal influenza vaccination (percentage increase: 5.39% vs. 1.44%), and promoted positive behavioral intention toward influenza vaccination (proportion of participants with positive change in vaccination intention: 17.46% vs. 7.69%). The study supports use of "Influenza Vaccination Reminder Application" to promote the behavior intention of influenza vaccination among pregnant women in Taiwan.

Analysis of HLA Variants and Graves' Disease and Its Comorbidities Using a High Resolution Imputation System to Examine Electronic Medical Health Records.

Hyperthyroidism is a prevalent endocrine disorder, and genetics play a major role in the development of thyroid-associated diseases. In particular, the inheritance of HLA has been demonstrated to induce the highest susceptibility to Graves' disease (GD). However, thus far, no studies have reported the contribution of HLA to the development of GD and the complications that follow. Thus, in the present study, to the best of our knowledge, for the first time, a powerful imputation method, HIBAG, was used to predict the HLA subtypes among populations with available genome-wide SNP array data from the China Medical University Hospital (CMUH). The disease status was extracted from the CMUH electronic medical records; a total of 2,998 subjects with GD were identified as the cases to be tested and 29,083 subjects without any diagnosis of thyroid disorders were randomly selected as the controls. A total of 12 HLA class I genotypes (HLA-A*02:07-*11:01, HLA-B*40:01-*46:01 and *46:01-*46:01, and HLA-C*01:02-*01:02, *01:02-*03:04, and *01:02-*07:02) and 17 HLA class II genotypes (HLA-DPA1*02:02-*02:02, HLA-DPB1*02:01-*05:01, *02:02-*05:01, and *04:01-*05:01, HLA-DQA1*03:02, HLA-DRB1*09:01-*15:01, and *09:01-*09:01) were found to be associated with GD in the Taiwanese population. Moreover, the HLA subtypes HLA-A*11:01, HLA-B*46:01, HLA-DPA1*01:03, and HLA-DPB1*05:01 were found to be associated with heart disease, stroke, diabetes, and hypertension among subjects with GD. Our data suggest that several HLA alleles are markedly associated with GD and its comorbidities, including heart disease, hypertension, and diabetes.

Thioacetamide-Induced Norepinephrine Production by Hepatocytes is Associated with Hepatic Stellate Cell Activation and Liver Fibrosis.

BACKGROUND: Collagen production by activated hepatic stellate cells (HSCs) to encapsulate injury is part of the natural wound-healing response in injured liver. However, persistent activation of HSCs can lead to pathological fibrogenesis. Such persistent HSC activation could be mediated by norepinephrine (NE), a reaction product of dopamine beta-hydroxylase (DBH). OBJECTIVE: To investigate the potential paracrine role of NE in hepatotoxin thioacetamide (TAA)-induced liver fibrosis. METHODS: In TAA-treated mice, fibrotic liver tissue showed significant increases in the mRNA expression of DBH up to 14-fold and collagen up to 7-fold. Immunohistochemical staining showed increased DBH protein expression in fibrotic liver tissue. Parenchymal hepatocyte cell line HepG2 expressed DBH and secreted NE, and the conditioned medium of HepG2 cells promoted collagenesis in nonparenchymal HSC cell line LX-2. TAA treatment increased DBH expression by 170% in HepG2 cells, as well as increased NE by 120% in the conditioned medium of HepG2 cells. The conditioned medium of TAA-treated HepG2 cells was used to culture LX-2 cells, and was found to increase collagen expression by 80% in LX-2 cells. Collagen expression was reduced by pre-treating HepG2 cells with siRNA targeting DBH or by adding NE antagonists to the conditioned medium. RESULTS: Finally, TAA-induced oxidative stress in HepG2 cells was associated with induction of DBH expression. Collectively, our results suggest a potential role for DBH/NE-mediated crosstalk between hepatocytes and HSCs in fibrogenesis. CONCLUSION: From a therapeutic standpoint, antagonism of DBH/NE induction in hepatocytes might be a useful strategy to suppress pathological fibrogenesis.