Knowledge and trust of mothers regarding childhood vaccination in Rwanda.

INTRODUCTION: Knowledge and trust are some of the contributing factors to vaccine acceptance(VA) and Vaccine hesitancy (VH) is one of the top threats to global health. A significant drop in childhood vaccination has been observed in recent years. One important reason that influences mothers' choice to either postpone or avoid children's vaccinations is knowledge and trust in childhood vaccines. This study aimed to assess mothers' knowledge and trust on vaccination of their children, and to examine the association between vaccination knowledge and selected socio-demographic factors. METHODS: A cross-sectional survey was conducted from January 2022 to March 2022 to assess the knowledge and trust of mothers regarding childhood vaccination. Data was collected with self-administered questionnaires. Multivariable logistic regression analysis was employed to assess factors associated with childhood vaccine knowledge and trust. RESULTS: Of the 2,126 Rwandan parents who participated in the study, the proportions with good knowledge of - and good trust in childhood vaccination were 95.5% and 91.4%, respectively. The popular sources of information about childhood vaccination were health care professionals (91.8%) and mass media (28.9%). Multinomial logistic regression analysis showed that good knowledge of - and trust in childhood vaccination were associated with the relationship with child(ren), education, occupation, and monthly income. The Multinomial logistic regression also revealed that the determinants of good knowledge of - and trust in childhood vaccination were; caregiver (p = 4.0 × 10-4, adjusted Odds Ratio (aOR); 1.7, 95%C.I; 1.3 - 2.3), no formal educational status (p = 3.3 × 10-2, aOR; 1.7, 95%C.I; 1.0 - 3.0), the unemployed occupational status (p = 2.4 × 10-2, aOR; 1.2, 95%C.I; 1.0 - 1.4), and persons on more than $401 per month (p = 2.0 × 10-4, aOR; 3.5, 95%C.I; 1.8 - 6.8). CONCLUSION: The majority of parents in Rwanda had both good knowledge of-and good trust regarding childhood vaccination. Public health strategies to promote vaccination, education programmes as well as improved communication tools between health care professionals/traditional leaders/religious leaders and parents need to be considered to achieve favourable vaccination attitudes and practices for all parents in Rwanda.

Repetitive peripheral magnetic stimulation combined with transcranial magnetic stimulation in rehabilitation of upper extremity hemiparesis following stroke: a pilot study.

OBJECTIVE: To investigate the effect of combined repetitive peripheral magnetic stimulation and transcranial magnetic stimulation on upper extremity function in subacute stroke patients. DESIGN: Pilot study. SUBJECTS: Subacute stroke patients. METHODS: Included patients were randomized into 3 groups: a central-associated peripheral stimulation (CPS) group, a central-stimulation-only (CS) group, and a control (C) group. The CPS group underwent a new paired associative stimulation (combined repetitive peripheral magnetic stimulation and transcranial magnetic stimulation), the CS group underwent repetitive transcranial magnetic stimulation, and the C group underwent sham stimulation. All 3 groups received physiotherapy after the stimulation or sham stimulation. The treatment comprised 20 once-daily sessions. Primary outcome was the Fugl-Meyer Assessment Upper Extremity (FMA-UE) score, and secondary outcomes were the Barthel Index and Comprehensive Functional Assessment scores, and neurophysiological assessments were mainly short-interval intracortical inhibition. A 3-group (CPS, CS, C) × 2-time (before, after intervention) repeated measures analysis of variance was conducted to determine whether changes in scores were significantly different between the 3 groups. RESULTS: A total of 45 patients were included in the analysis. Between-group comparisons on the FMA-UE demonstrated a significant improvement (group × time interaction, F2,42 = 4.86; p = 0.013; C vs CS, p = 0.020; C vs CPS, p = 0.016; CS vs CPS, p = 0.955). Correlation analysis did not find any substantial positive correlation between changes in FMA-UE and short-interval intracortical inhibition variables (C, r = -0.196, p = 0.483; CS, r = -0.169, p = 0.546; CPS, r = -0.424, p = 0.115). CONCLUSION: This study suggests that the real-stimulus (CS and CPS) groups had better outcomes than the control (C) group. In addition, the CPS group showed a better trend in clinical and neurophysiological assessments compared with the CS group.

The global economic burden of chronic obstructive pulmonary disease for 204 countries and territories in 2020-50: a health-augmented macroeconomic modelling study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide and imposes a substantial economic burden. Gaining a thorough understanding of the economic implications of COPD is an important prerequisite for sound, evidence-based policy making. We aimed to estimate the macroeconomic burden of COPD for each country and establish its distribution across world regions. METHODS: In this health-augmented macroeconomic modelling study we estimated the macroeconomic burden of COPD for 204 countries and territories over the period 2020-50. The model accounted for (1) the effect of COPD mortality and morbidity on labour supply, (2) age and sex specific differences in education and work experience among those affected by COPD, and (3) the impact of COPD treatment costs on physical capital accumulation. We obtained data from various public sources including the Global Burden of Disease Study 2019, the World Bank database, and the literature. The macroeconomic burden of COPD was assessed by comparing gross domestic product (GDP) between a scenario projecting disease prevalence based on current estimates and a counterfactual scenario with zero COPD prevalence from 2020 to 2050. FINDINGS: Our findings suggest that COPD will cost the world economy INT$4·326 trillion (uncertainty interval 3·327-5·516; at constant 2017 prices) in 2020-50. This economic effect is equivalent to a yearly tax of 0·111% (0·085-0·141) on global GDP. China and the USA face the largest economic burdens from COPD, accounting for INT$1·363 trillion (uncertainty interval 1·034-1·801) and INT$1·037 trillion (0·868-1·175), respectively. INTERPRETATION: The macroeconomic burden of COPD is large and unequally distributed across countries, world regions, and income levels. Our study stresses the urgent need to invest in global efforts to curb the health and economic burdens of COPD. Investments in effective interventions against COPD do not represent a burden but could instead provide substantial economic returns in the foreseeable future. FUNDING: Alexander von Humboldt Foundation, National Natural Science Foundation of China, CAMS Innovation Fund for Medical Science, Chinese Academy of Engineering project, Chinese Academy of Medical Sciences and Peking Union Medical College project, and Horizon Europe. TRANSLATIONS: For the Chinese and German translations of the abstract see Supplementary Materials section.

The enhancement of mechanical properties and uniform degradation of electrodeposited Fe-Zn alloys by multilayered design for biodegradable stent applications.

Pure Fe is a potential biodegradable stent material due to its better biocompatibility and mechanical properties, but its degradation rate needs to be improved. Alloying with Zn to form Fe-Zn alloy is anticipated to meet the degradation rate requirements while retaining the iron's inherent properties. Therefore, Fe-Zn alloys with monolayered and multilayered structures were prepared by electrodeposition. The alloys' composition, microstructure, mechanical properties, in vitro degradation and biocompatibility were assessed. Results showed that the Zn content ranged from 2.1 wt% to 11.6 wt%. After annealing at 450°C, all the alloys consisted of α(Fe) solid solution and Zn-rich B2 ordered coherent phase, except for the alloy with 11.6 wt% Zn content, in which a Fe3Zn10 phase appeared. The layered structure consisted of alternating columnar-grain and nano-grain layers, which compensated for the intrinsic brittleness of electrodeposited metals and improved the galvanic effect of the alloy, thus increasing the strength and plasticity and changing the corrosion from localized to uniform while augmenting the corrosion rate. The yield strength of the multilayered alloy exceeded 350 MPa, its elongation was more than 20%, and its corrosion rate obtained by immersion test in Hank's solution reached 0.367 mm·y-1. Fe-Zn alloys with lower Zn content had good cytocompatibility with the human umbilical vein endothelial cells and good blood compatibility. The above results verified that the multilayered Fe-Zn alloy prepared by electrodeposition presented enhanced mechanical properties, higher degradation rate, uniform degradation mechanism and good biocompatibility. It should be qualified for the application of biodegradable stents. STATEMENT OF SIGNIFICANCE: A potential biodegradable Fe-Zn alloy, which is difficult to be obtained by the metallurgical method, was prepared by electrodeposition to solve the low degradation rate of iron-based biomaterials. A multilayered microstructure design composed of alternating columnar-grain and nano-grain layers was achieved by changing the electrical parameters. The layered design compensated for the intrinsic poor plasticity of electrodeposited metals. It increased the galvanic effect of the alloy, thus augmenting the corrosion rate and changing the corrosion mode of the alloy from localized to uniform corrosion. The yield strength of multilayered alloy exceeded 350 MPa; its elongation was more than 20%. Moreover, the layered alloy had good cytocompatibility and blood compatibility. It indicates that the alloy is qualified for biodegradable stent application.

Hope as a predictor for COVID-19 vaccine uptake in the US: a cross-sectional survey of 11,955 adults.

Widespread vaccine uptake is critical for ending the COVID-19 pandemic. As public health officials focus on overcoming vaccine hesitancy, simultaneously boosting hope may be equally important in the US. We analyzed data from an online cross-sectional survey conducted in June 2021. Participants were 11,955 US adults (ages 18-83) of various ethnicities, living in urban and rural settings. Of these, 71.3% had some college education. Mean age was 32.3 years and 72.4% reported being vaccinated against COVID-19. Main measures were COVID-19 self-reported vaccination status (vaccine uptake), vaccine hesitancy (Adult Vaccine Hesitancy Scale), and hope (Adult Hope Scale). The US grand mean hope score fell within the low-hope range. COVID-19 vaccine uptake was positively associated with hope, even after adjusting for vaccine hesitancy, gender, age, ethnicity, income, and urban vs. rural residence. The strong relationship between hope, vaccine confidence and vaccine uptake persisted across US populations at risk for low vaccine uptake. Our mediation analysis revealed that, for every unit increase in hope, the probability of being vaccinated went up by 5% points. Of this association, 52% was not mediated by vaccine hesitancy, but rather through a direct pathway from hope to vaccine uptake. Mediation analyses of US populations at risk of low vaccine uptake revealed similar findings. Hope may play an important role in vaccine uptake by reducing vaccine hesitancy and by directly enhancing vaccine uptake. Especially in populations at risk of low vaccine uptake, vaccine interventions that boost hope may augment public health efforts to increase US vaccination rates.

Trends of overweight and obesity among preschool children from 2013 to 2018: a cross-sectional study in Rhine-Neckar County and the City of Heidelberg, Germany.

BACKGROUND: Early childhood overweight and obesity is a growing public health concern worldwide. Few recent studies have addressed how time trends varied by sociodemographic characteristics at the regional level using large and high-quality data. This study determines how time trends vary in the prevalence of early childhood overweight and obesity by age, gender, and migration background at the regional level. METHODS: We used a Kernel-density curve to describe the BMI distribution, and evaluated the trends of overweight and obesity by age, gender, and migration background using logistic regression. RESULTS: Mean BMI and the overall prevalence of overweight and obesity increased among preschool children aged 4-6 years in the Rhine-Neckar County and the City of Heidelberg. After adjusting for age, sex, and migration background, trends of overweight significantly increased only among male children in the age 5 year group with migration background (P < 0.05), and an upward trend of obesity was observed only among male children in the age 5 year group and female children in the age 6 year group with migration background (P < 0.05). CONCLUSIONS: BMI distribution as well as general prevalence of overweight and obesity are still increasing among preschool children. Children with migration backgrounds, particularly male children in the age 5 year groups and female children in the age 6 year group should be prioritized. Health promotion strategies for children with migration backgrounds will help address this challenge.

Attitudes Toward the Global Allocation of Chinese COVID-19 Vaccines: Cross-sectional Online Survey of Adults Living in China.

BACKGROUND: COVID-19 vaccines are in short supply worldwide. China was among the first countries to pledge supplies of the COVID-19 vaccine as a global public product, and to date, the country has provided more than 600 million vaccines to more than 200 countries and regions with low COVID-19 vaccination rates. Understanding the public's attitude in China toward the global distribution of COVID-19 vaccines could inform global and national decisions, policies, and debates. OBJECTIVE: The aim of this study was to determine the attitudes of adults living in China regarding the global allocation of COVID-19 vaccines developed in China and how these attitudes vary across provinces and by sociodemographic characteristics. METHODS: We conducted a cross-sectional online survey among adults registered with the survey company KuRunData. The survey asked participants 31 questions about their attitudes regarding the global allocation of COVID-19 vaccines developed in China. We disaggregated responses by province and sociodemographic characteristics. All analyses used survey sampling weights. RESULTS: A total of 10,000 participants completed the questionnaire. Participants generally favored providing COVID-19 vaccines to foreign countries before fulfilling domestic needs (75.6%, 95% CI 74.6%-76.5%). Women (3778/4921, 76.8%; odds ratio 1.18, 95% CI 1.07-1.32; P=.002) and those living in rural areas (3123/4065, 76.8%; odds ratio 1.13, 95% CI 1.01-1.27; P=.03) were especially likely to hold this opinion. Most respondents preferred providing financial support through international platforms rather than directly offering support to individual countries (72.1%, 95% CI 71%-73.1%), while for vaccine products they preferred direct provision to relevant countries instead of via a delivery platform such as COVAX (77.3%, 95% CI 76.3%-78.2%). CONCLUSIONS: Among our survey sample, we found that adults are generally supportive of the international distribution of COVID-19 vaccines, which may encourage policy makers to support and implement the distribution of COVID-19 vaccines developed in China worldwide. Conducting similar surveys in other countries could help align policy makers' actions on COVID-19 vaccine distribution with the preferences of their constituencies.

Prevalence of depression in China during the early stage of the COVID-19 pandemic: a cross-sectional study in an online survey sample.

OBJECTIVES: We aimed to determine (1) the prevalence of depression during the COVID-19 pandemic among Chinese adults and (2) how depression prevalence varied by province and sociodemographic characteristics. DESIGN: Cross-sectional study. SETTING: National online survey in China. PARTICIPANTS: We conducted a cross-sectional online survey among adults registered with the survey company KuRunData from 8 May 2020 to 8 June 2020. We aimed to recruit 300-360 adults per province (n=14 493), with a similar distribution by sex and rural-urban residency as the general population within each of these provinces. PRIMARY OUTCOME: Participants completed the Patient Health Questionaire-9 (PHQ-9). We calculated the prevalence of depression (defined as a PHQ-9 score ≥10) nationally and separately for each province. ANALYSIS: Covariate-unadjusted and covariate-adjusted logistic regression models were used to examine how the prevalence of depression varied by adults' sociodemographic characteristics. All analyses used survey sampling weights. RESULTS: The survey was initiated by 14 493 participants, with 10 000 completing all survey questions and included in the analysis. The prevalence of depression in the national sample was 6.3% (95% CI 5.7% to 6.8%). A higher odds of depression was associated with living in an urban area (OR 1.50; 95% CI 1.18 to 1.90) and working as a nurse (OR 3.06; 95% CI 1.41 to 6.66). A lower odds of depression was associated with participants who had accurate knowledge of COVID-19 transmission prevention actions (OR 0.71; 95% CI 0.51 to 0.98), the knowledge that saliva is a main transmission route (OR 0.80; 95% CI 0.64 to 0.99) and awareness of COVID-19 symptoms (OR, 0.82; 95% CI 0.68 to 1.00). CONCLUSION: Around one in 20 adults in our online survey sample had a PHQ-9 score suggestive of depression. Interventions and policies to prevent and treat depression during the COVID-19 pandemic in China may be particularly needed for nurses and those living in urban areas.

Animated, video entertainment-education to improve vaccine confidence globally during the COVID-19 pandemic: an online randomized controlled experiment with 24,000 participants.

BACKGROUND: Science-driven storytelling and entertainment-education (E-E) media demonstrate potential for promoting improved attitudes and behavioral intent towards health-related practices. Months after the outbreak of coronavirus disease 2019 (COVID-19), emerging research highlights the essential role of interventions to improve public confidence in the COVID-19 vaccine. To improve vaccine confidence, we designed three short, animated videos employing three research-informed pedagogical strategies. These can be distributed globally through social media platforms, because of their wordless and culturally accessible design. However, the effectiveness of short, animated storytelling videos, deploying various pedagogic strategies, needs to be explored across different global regions. METHODS/DESIGN: The present study is a multi-site, parallel group, randomized controlled trial (RCT) comparing the effectiveness of (i) a storytelling-instructional-humor approach, (ii) a storytelling-analogy approach, (iii) a storytelling-emotion-focused approach, and (iv) no video. For our primary outcomes, we will measure vaccine hesitancy, and for secondary outcomes, we will measure behavioral intent to seek vaccination and hope. Using online platforms, we will recruit 12,000 participants (aged 18-59 years) from the USA and China, respectively, yielding a total sample size of 24,000. DISCUSSION: This trial uses innovative online technology, reliable randomization algorithms, validated survey instruments, and list experiments to establish the effectiveness of three short, animated videos employing various research-informed pedagogical strategies. Results will be used to scientifically support the broader distribution of these short, animated video as well as informing the design of future videos for rapid, global public health communication. TRIAL REGISTRATION: German Clinical Trials Register DRKS #00023650 . Date of registration: 2021/02/09.

Sex-Specific Development in Haplodiploid Honeybee Is Controlled by the Female-Embryo-Specific Activation of Thousands of Intronic LncRNAs.

Embryonic development depends on a highly coordinated shift in transcription programs known as the maternal-to-zygotic transition (MZT). It remains unclear how haploid and diploid embryo coordinate their genomic activation and embryonic development during MZT in haplodiploid animals. Here, we applied a single-embryo RNA-seq approach to characterize the embryonic transcriptome dynamics in haploid males vs. diploid females of the haplodiploid insect honeybee (Apis mellifera). We observed typical zygotic genome activation (ZGA) occurred in three major waves specifically in female honeybee embryos; haploid genome activation was much weaker and occurred later. Strikingly, we also observed three waves of transcriptional activation for thousands of long non-coding transcripts (lncRNA), 73% of which are transcribed from intronic regions and 65% were specific to female honeybee embryos. These findings support a model in which introns encode thousands of lncRNAs that are expressed in a diploid-embryo-specific and ZGA-triggered manner that may have potential functions to regulate gene expression during early embryonic development in the haplodiploid insect honeybee.

Correction: Knowledge About COVID-19 Among Adults in China: Cross-sectional Online Survey.

[This corrects the article DOI: 10.2196/26940.].

Corrigendum: The After-Effect of Accelerated Intermittent Theta Burst Stimulation at Different Session Intervals.

[This corrects the article DOI: 10.3389/fnins.2020.00576.].

Knowledge About COVID-19 Among Adults in China: Cross-sectional Online Survey.

BACKGROUND: A detailed understanding of the public's knowledge and perceptions of COVID-19 could inform governments' public health actions in response to the pandemic. OBJECTIVE: The aim of this study was to determine the knowledge and perceptions of COVID-19 among adults in China and its variation among provinces and by sociodemographic characteristics. METHODS: Between May 8 and June 8, 2020, we conducted a cross-sectional online survey among adults in China who were registered with the private survey company KuRunData. We set a target sample size of 10,000 adults, aiming to sample 300-360 adults from each province in China. Participants were asked 25 questions that tested their knowledge about COVID-19, including measures to prevent infection, common symptoms, and recommended care-seeking behavior. We disaggregated responses by age; sex; education; province; household income; rural-urban residency; and whether or not a participant had a family member, friend, or acquaintance who they know to have been infected with SARS-CoV-2. All analyses used survey sampling weights. RESULTS: There were 5079 men and 4921 women who completed the questionnaire and were included in the analysis. Out of 25 knowledge questions, participants answered a mean and median of 21.4 (95% CI 21.3-21.4) and 22 (IQR 20-23) questions correctly, respectively. A total of 83.4% (95% CI 82.7%-84.1%) of participants answered four-fifths or more of the questions correctly. For at least one of four ineffective prevention measures (using a hand dryer, regular nasal irrigation, gargling mouthwash, and taking antibiotics), 68.9% (95% CI 68.0%-69.8%) of participants answered that it was an effective method to prevent a SARS-CoV-2 infection. Although knowledge overall was similar across provinces, the percent of participants who answered the question on recommended care-seeking behavior correctly varied from 47.0% (95% CI 41.4%-52.7%) in Tibet to 87.5% (95% CI 84.1%-91.0%) in Beijing. Within provinces, participants who were male, were middle-aged, were residing in urban areas, and had higher household income tended to answer a higher proportion of the knowledge questions correctly. CONCLUSIONS: This online study of individuals across China suggests that the majority of the population has good knowledge of COVID-19. However, a substantial proportion still holds misconceptions or incorrect beliefs about prevention methods and recommended health care-seeking behaviors, especially in rural areas and some less wealthy provinces in Western China. This study can inform the development of tailored public health policies and promotion campaigns by identifying knowledge areas for which misconceptions are comparatively common and provinces that have relatively low knowledge.

The After-Effect of Accelerated Intermittent Theta Burst Stimulation at Different Session Intervals.

OBJECTIVE: The study aims to investigate the after-effect of three sessions of intermittent theta-burst stimulation (iTBS) on motor cortical excitability. The iTBS was induced over the primary motor cortex (M1) at different time intervals. METHODS: The study has a crossover design. Sixteen participants were assigned to three groups and received different accelerated iTBS (aiTBS) protocols during each visit: (1) three continuous sessions with no interval (iTBS18000); (2) three iTBS sessions with 10-min intervals (iTBS600 × 3∗10); and (3) three iTBS sessions with 30-min intervals (iTBS600 × 3∗30). As washout period, each visit is separated by at least 7 days. We measured the motor cortical excitability changes and intracortical inhibition. RESULTS: A dose of 1,800 pulses of aiTBS per day is tolerable. The iTBS1800 led to a reduced cortical excitability; whereas iTBS600 × 3∗10 and iTBS600 × 3∗30 enhanced cortical excitability to a differential extent. After a total dose of 1,800 pulses, iTBS600 × 3∗30 exhibited the longer effect and highest percentage of individuals with enhanced cortical excitability. CONCLUSION: The results suggest that aiTBS protocols at different time intervals result in different motor cortical excitability after-effects.

Poly(A)-seq: A method for direct sequencing and analysis of the transcriptomic poly(A)-tails.

Poly(A) tails at the 3' end of eukaryotic messenger RNAs control mRNA stability and translation efficiency. Facilitated by various NGS methods, alternative polyadenylation sites determining the 3'-UTR length of gene transcripts have been extensively studied. However, poly(A) lengths demonstrating dynamic and developmental regulation remain largely unexplored. The recently developed NGS-based methods for genome-wide poly(A) profiling have promoted the study of genom-wide poly(A) dynamics. Here we present a straight forward NGS-method for poly(A) profiling, which applies a direct 3'-end adaptor ligation and the template switching for 5'-end adaptor ligation for cDNA library construction. Poly(A) lengths are directly calculated from base call data using a self-developed pipeline pA-finder. The libraries were directly sequenced from the 3'-UTR regions into the followed poly(A) tails, firstly on NextSeq 500 to produce single-end 300-nt reads, demonstrating the method feasibility and that optimization of the fragmented RNA size for cDNA library construction could detecting longer poly (A) tails. We next applied Poly(A)-seq cDNA libraries containing 40-nt and 120-nt poly(A) tail spike-in RNAs on HiSeq X-ten and NovaSeq 6000 to obtain 150-nt and 250-nt pair-end reads. The sequencing profiles of the spike-in RNAs demonstrated both high accuracy and high quality score in reading poly(A) tails. The poly(A) signal bleeding into the 3' adaptor sequence and a sharp decreased quality score at the junction were observed, allowing the modification of pA-finder to remove homopolymeric signal bleeding. We hope that wide applications of Poly(A)-seq help facilitate the study of the development- and disease-related poly(A) dynamics and regulation, and of the recent emerging mixed tailing regulation.

Characterization and cytocompatibility of hierarchical porous TiO2 coatings incorporated with calcium and strontium by one-step micro-arc oxidation.

Calcium (Ca) and strontium (Sr) are beneficial for bone reconstruction. This study incorporated Ca and Sr into the TiO2 coatings by one-step micro-arc oxidation (MAO) treatment with CaO and SrO added in tetraborate electrolytes. The structure, composition, hydrophilicity, ion release, and cytocompatibility of the coatings were studied. The coatings combine layered micron-scale pores in various sizes and nano-scaled pores, forming a hierarchical structure. This hierarchical structure is highly porous and super-hydrophilic. The coatings are composed of Ti, O, and B, as well as Ca or Sr. Ca and Sr mainly distribute in the outer layer of the coatings and exist in the forms of carbonates and oxides. The formation of the coatings was discussed. Ca and Sr incorporated into the coatings are readily released into aqueous solutions. The homogeneous surface structure of the coatings leads to an excellent and approximating performance in hydrophilicity, as well as the adhesion and spreading of the human bone marrow-derived mesenchymal stem cells (hBMSCs). The simultaneous incorporation of Ca and Sr incorporation exhibits superior facilitation in the proliferation of hBMSCs compared with single Ca or Sr incorporation. This study shows a promising method to incorporate bioactive elements into the MAO coatings on titanium surfaces.

Tristetraprolin-RNA interaction map reveals a novel TTP-RelB regulatory network for innate immunity gene expression.

Tristetraprolin (TTP) regulates inflammatory and immune responses by destabilizing target mRNAs via binding to their 3'-UTR AREs. We have recently reported that TTP preferentially up-regulates the expression level of innate immunity genes involved in the type I interferon-mediated signaling pathway and viral response in cancer cells. To elucidate the role of TTP-RNA interaction in TTP-mediated upregulation of gene expression, we performed iRIP-seq experiments to obtain the RNA interaction map consisting of direct and indirect binding sites of TTP in HeLa cells. We found substantial TTP binding signals in mRNA regions and the introns. ARE-motif AUUUA is over-represented in TTP binding peaks. Strikingly, AUUUA frequency is high both in 3'UTR and intronic regions, and the intronic peaks were more associated with TTP-regulated genes. Analysis of the over-represented motifs in TTP peaks revealed the high frequencies of UAGG and GUGUG motifs reported for hnRNPA2/B1 and CELF1 respectively in the 3'UTR and introns, and also the UGGAC motif overlapping with the m6A motif GGACU in the CDS regions. We further demonstrated that TTP binds to multiple intronic and exonic sites in the pre-mRNA/mRNA of the transcription factor RelB, correlating with the TTP-upregulated expression of RelB. TTP-up-regulated genes without a TTP binding site, but not those with, are highly enriched in innate immunity pathways and show higher tendency of harboring RelB binding sites in their promoter regions. These findings support a model in which TTP binding of RelB pre-mRNA/mRNA coordinates the RelB upregulation and activation of the innate immunity for antiviral response.

Induced Expression of VEGFC, ANGPT, and EFNB2 and Their Receptors Characterizes Neovascularization in Proliferative Diabetic Retinopathy.

Purpose: To investigate whole transcriptional differences between proliferative diabetic retinopathy (PDR) neovascular membranes (NVMs) and retinas, and the regulatory genes participating in retinal neovascularization in PDR. Methods: We used high-throughput sequencing technology to capture the whole-genome gene expression levels of all participants, including 23 patients with PDR or branch retinal vein occlusion (BRVO), 3 normal retinal samples, and 2 retinal samples from type II diabetic (T2D) eyes by donation, followed by analyses of expression patterns using bioinformatics methods, then validation of the data by in situ hybridization and Western blotting. Results: We showed that transcriptional profiles of the NVMs were distinct from those of the retinas. Angiogenesis growth factors VEGFC, ANGPT1, ANGPT2, and EFNB2, and their receptors FLT4, TIE1, TIE2, and EPHB4, respectively, were overexpressed. Expression of VEGFA was highly upregulated in T2D retina, but low in the NVMs, while angiogenesis transcription factors, including ETS1 and ERG, were coordinately upregulated in NVMs. Conclusions: This study described a PDR neovascularization model in which pathological retina-secreted vascular endothelial growth factor A (VEGFA) enhanced the expression of a set of angiogenesis transcription factors and growth factors, to cooperatively induce the retinal neovascularization. Based on these results, novel potential therapeutic targets and biomarkers for PDR treatment and diagnosis are suggested.

Tristetraprolin specifically regulates the expression and alternative splicing of immune response genes in HeLa cells.

BACKGROUND: Tristetraprolin (TTP) is an RNA binding protein that plays a critical role in regulating proinflammatory immune responses by destabilizing target mRNAs via binding to their AU-rich elements (AREs) in the 3'-UTRs of mRNAs. A recent CLIP-seq study revealed that TTP-binding sites are enriched in the intronic regions of RNA. TTP is also a nuclear protein that exhibits putative DNA-binding activity. These features suggested that TTP might regulate gene transcription and/or alternative splicing of pre-mRNAs in the absence of stimulation. RESULTS: To elucidate the regulatory pattern of TTP, we cloned and overexpressed the human TTP-encoding gene, ZFP36, in HeLa cells in the absence of inflammatory stimuli. The transcriptomes of the control and ZFP36-overexpressing cells were sequenced and subjected to analysis and validation. Upon ZFP36 overexpression, the expression of genes associated with innate immunity, including those in the type I interferon signaling pathway and viral response, were specifically upregulated, implying a transcriptional regulatory mechanism associated with the predicted DNA binding activity of TTP. TTP preferentially regulated the alternative splicing of genes involved in the positive regulation of the I-κB/NF-κB cascade and the TRIF-dependent toll-like receptor, MAPK, TNF, and T cell receptor signaling pathways. CONCLUSIONS: Our findings indicated that TTP may regulate the immune response via the regulation of alternative splicing and potentially transcription, which greatly expands the current understanding of the mechanisms of TTP-mediated gene regulation.

Transcriptome analysis reveals downregulation of virulence-associated genes expression in a low virulence Verticillium dahliae strain.

Verticillium dahliae causes wilt diseases and early senescence in numerous plants, including agricultural crops such as cotton. In this study, we studied two closely related V. dahliae strains, and found that V991w showed significantly reduced virulence on cotton than V991b. Comprehensive transcriptome analysis revealed various differentially expressed genes between the two strains, with more genes repressed in V991w. The downregulated genes in V991w were involved in production of hydrophobins, melanin, predicted aflatoxin, and membrane proteins, most of which are related to pathogenesis and multidrug resistance. Consistently, melanin production in V991w in vitro was compromised. We next obtained genomic variations between the two strains, demonstrating that transcription factor genes containing fungi specific transcription factor domain and fungal Zn2-Cys6 binuclear cluster domain were enriched in V991w, which might be related to pathogenicity-related genes downregulation. Thus, this study supports a model in which some virulence factors involved in V. dahliae pathogenicity were pre-expressed during in vitro growth before host interaction.