Non-targeted metabolomics reveals the taste variations during Baccaurea ramiflora Lour. fruit maturation.

Baccaurea ramiflora Lour. is a new kind of underutilized wild fruit tree; the metabolic reasons for its fruit flavor changes are not yet clear. In this study, the pink flesh of this excellent tasting fruit (BR) was used to reveal the metabolic causes of taste variations through five developmental stages. We identified 154 common differential metabolites of different developmental stages based on non-targeted metabolomics analysis. The accumulation of sugar and fatty acids increased significantly after 73 days, while citric acid decreased significantly. Flesh color accumulation mainly occurred 53 days ago, and vitamin accumulation occurred after 93 days. Interestingly, L-sorbose and 5-hydroxyindole-3-acetic acid were positively correlated with the sugar-acid ratio but negatively correlated with titratable acids. It indicated that L-sorbose and 5-hydroxyindole-3-acetic acid may be taste biomarkers of BR B. ramiflora. The results provided new metabolic lines of evidence for the taste variation during the ripening process of B. ramiflora.

Interleukin-36 is overexpressed in human sepsis and IL-36 receptor deletion aggravates lung injury and mortality through epithelial cells and fibroblasts in experimental murine sepsis.

BACKGROUND: Sepsis is defined as a life-threatening syndrome caused by an unbalanced host response to infection. The role of interleukin (IL)-36 cytokines binding to the IL-36 receptor (IL-36R) in host response during sepsis remains unknown. METHODS: Serum IL-36 level was measured in 47 septic patients sampled on the day of intensive care unit (ICU) and emergency department admission, 21 non-septic ICU patient controls, and 21 healthy volunteers. In addition, the effects of IL-36R deletion on host inflammatory response in cecal ligation and puncture (CLP)-induced polymicrobial sepsis was determined. RESULTS: On the day of ICU and emergency department admission, the patients with sepsis showed a significant increase in serum IL-36 levels compared with ICU patient controls and healthy volunteers, and the serum IL-36 levels were related to the severity of sepsis. Non-survivors of septic patients displayed significantly lower serum IL-36 levels compared with survivors. A high serum IL-36 level in ICU and emergency department admission was associated with 28-day mortality, and IL-36 was found to be an independent predictor of 28-day mortality in septic patients by logistic regression analysis. Furthermore, IL-36R deletion increased lethality in CLP-induced polymicrobial sepsis. Septic mice with IL-36R deletion had higher bacterial load and demonstrated more severe multiple organ injury (including lung, liver, and kidney) as indicated by clinical chemistry and histopathology. Mechanistically, IL-36R ligands released upon lung damage activated IL-36R+lung fibroblasts thereby inducing expression of the antimicrobial protein lipocalin 2. Moreover, they induced the apoptosis of lung epithelial cells. CONCLUSIONS: Septic patients had elevated serum IL-36 levels, which may correlate with disease severity and mortality. In experimental sepsis, we demonstrated a previously unrecognized role of IL-36R deletion in increasing lethality.

Fabrication of Enzyme-Responsive Prodrug Self-Assembly Based on Fluazinam for Reducing Toxicity to Aquatic Organisms.

Prodrug-based nanodrug delivery systems were drug formulations by covalently conjugating drugs with inversely polar groups via a cleavable bond to self-assemble into nanoparticles for efficient drug delivery. To improve the utilization efficiency of fluazinam (FZN), enzyme-responsive prodrugs were prepared by conjugating FZN with different alkyl aliphatic acids through a nucleophilic substitution reaction and subsequently self-assembled into nanoparticles (FZNP NPs) without using any harmful adjuvant. The obtained FZNP NPs exhibited excellent efficacies against Sclerotinia sclerotiorum as a result of improved physicochemical properties, including low surface tension, high retention, and enhanced photostability. The LC50 values of FZNP NPs toward zebrafish were 3-8 times that of FZN, which illustrated that the FZNP NPs reduced the detriments of FZN to the aquatic organisms while retaining good biological activity. Therefore, prodrug self-assembly technology would offer a potential method for improving the utilization efficiency of pesticides and lowering the risks to the ecological environment.

A high adhesion co-assembly based on myclobutanil and tannic acid for sustainable plant disease management.

BACKGROUND: Pesticides are irreplaceable inputs for protecting crops from pests and improving crop yield and quality. Self-assembly nanotechnology is a promising strategy by which to develop novel nano-formulations for pesticides. Nano-formulations improve the effective utilization of pesticides and reduce risks to the environment because of their eco-friendly preparation, high drug loading, and desirable physicochemical properties. Here, to enhance the utilization efficiency of myclobutanil (MYC) and develop a novel nano-formulation, carrier-free co-assembled nanoparticles (MT NPs) based on MYC and tannic acid (TA) were prepared by noncovalent molecular interactions using a green preparation process without any additives. RESULTS: The results showed that the prepared spherical nanoparticles had good stability in neutral and acidic aqueous solutions, low surface tension (40.53 mN m-1 ), high rainfastness, and good maximum retention values on plant leaves. Release of active ingredients from MT NPs could be regulated by altering the molar ratio of subassemblies in the co-assembly and the pH of the environment. Antifungal experiments demonstrated that MT NPs had better activities against Alternaria alternata and Fusarium graminearum [half-maximal effective concentration (EC50 ) = 6.40 and 77.08 mg/L] compared with free MYC (EC50 = 11.46 and 124.82 mg/L), TA (EC50 = 251.19 and 503.81 mg/L), and an MYC + TA mixture (EC50 = 9.62 and 136.21 mg/L). These results suggested that MYC and TA incorporated in the co-assembled nanoparticles had a synergistic antifungal activity. The results of a genotoxicity assessment indicated that MT NPs could reduce the genotoxicity of MYC to plant cells. CONCLUSION: Co-assembled MT NPs with synergistic antifungal activity have outstanding potential for the management of plant diseases. © 2023 Society of Chemical Industry.

Stable Fluorescent Nanoparticles Based on Co-assembly of Acifluorfen and Poly(salicylic acid) for Enhancing Herbicidal Activity and Reducing Environmental Risks.

Herbicides are widely used in modern agricultural production for their advantages of high efficiency, convenience, and speed. However, there have been many problems caused by herbicide formulations, such as volatilization, leaching, and rain-washing loss in the process of agricultural application. Self-assembled nanotechnology is a promising strategy to solve these existing problems due to the environmentally friendly preparation process and high delivery efficiency. In this study, the stable fluorescent nanoparticles (AP NPs) based on co-assembly of acifluorfen (ACI) and poly(salicylic acid) (PSA) are constructed by using non-covalent bond interactions. The results indicate that the obtained nanoparticles with a stable fluorescence characteristic show improved physiochemical properties, such as uniform morphology, good thermal stability, low surface tension, and high retention on plants. The co-assembly can produce singlet oxygen to enhance the herbicidal activity under irradiation of light and reduce the leaching property of ACI to minimize the adverse impact on the aquatic environment. The safety evaluation of soybean seedlings indicates that AP NPs have no damage to non-target plants. In summary, the co-assembled herbicidal nano-formulation composed of ACI and PSA has high bioactivity and low environmental risks, which can be widely used in agricultural production.

Self-Assembled Nanoparticles of a Prodrug Conjugate Based on Pyrimethanil for Efficient Plant Disease Management.

Self-assembled nanotechnology is a promising strategy for improving the effective utilization of pesticides due to its distinct advantages. Herein, an amide-bonded prodrug conjugate based on pyrimethanil (PYR) and butyric acid (BA) was successfully synthesized by the nucleophilic substitution reaction and subsequently self-assembled into spherical nanoparticles (PB NPs) with an average size of 85 nm through the solvent exchange method without using any toxic adjuvant. The results showed that PB NPs based on PYR and BA had a synergistic antimicrobial activity against S. sclerotiorum on plant leaves due to good photostability, low volatilization, good surface activity, and improved retention. Additionally, PB NPs could be used by plant cells as nutrients to promote the growth of plants and thus reduced the toxicity of PYR to plant. Therefore, this prodrug conjugate self-assembly nanotechnology would provide a promising strategy for improving the effective utilization rates of pesticides and reducing their toxicities to plants.

Genetic liability between COVID-19 and heart failure: evidence from a bidirectional Mendelian randomization study.

BACKGROUND: Previous studies have observed inconsistent associations between coronavirus disease 2019 (COVID-19) and heart failure (HF), but these studies were prone to bias based on reverse causality and residual confounding factors. We aimed to investigate genetic liability between COVID-19 and heart failure using a bidirectional Mendelian randomization study. METHODS: The causal relationship between COVID-19 (including COVID-19, hospitalized COVID-19 compared with the general population, and severe COVID-19) and HF are determined by using a bidirectional Mendelian randomization analysis. We drew on summary statistics from the largest HF genome-wide association study (GWAS) meta-analysis on individuals of European ancestry, which included 47,309 HF patients and 930,014 controls. The inverse variance weighted (IVW), an adaption of the Egger regression (MR-Egger), the weighted median, and weighted model were conducted for the Mendelian randomization analysis to estimate a causal effect. To confirm the stability, we performed a "leave-one-out" approach for the sensitivity analysis. RESULTS: Genetically predicted severe COVID-19 was not significantly associated with the risk of HF [odds ratio (OR), 1.003; 95% confidence interval (CI), 0.969-1.037; p = 0.867]. The IVW demonstrated that there was no association between genetically hospitalized COVID-19 infection and HF risk [OR, 1.009; 95% CI, 0.939-1.085; p = 0.797]. There was no evidence to support the association between genetically determined COVID-19 and the risk of HF [OR, 1.066; 95% CI, 0.955-1.190; p = 0.253]. In addition, genetically predicted HF was also not causally associated with COVID-19 [OR, 1.162; 95% CI, 0.824-1.639; p = 0.393]. MR-Egger analysis indicated no evidence of directional pleiotropy. CONCLUSION: The current bidirectional Mendelian randomization analysis overcomes the limitations of observational studies. Our findings indicated that there is no causal association between COVID-19 and HF.

Nap effects on preschool children's learning of letter-sound mappings.

This study explored whether a daytime nap aids children's acquisition of letter-sound knowledge, which is a fundamental component for learning to read. Thirty-two preschool children in Sydney, Australia (Mage  = 4 years;3 months) were taught letter-sound mappings in two sessions: one followed by a nap and the other by a wakeful period. Learning was assessed by explicit letter-sound mappings ("Which sound does this letter make?") and knowledge generalization tasks ("Here's Tav and Cav, which one is /kav/?"). Results from the knowledge generalization task showed better performance after a nap than after wake. However, no nap benefit was found for explicit letter-sound knowledge. This study provides initial evidence that naps could be beneficial for preschool children's learning of letter-sound mappings.

Supramolecular Self-Assembly of Herbicides with Reduced Risks to the Environment.

The side effects caused by some pesticides with high off-target movement have brought great risks to the environment and human health. Here, taking 2,4-dichlorophenoxyacetic acid (2,4-D) as a model herbicide to reduce its volatilization and leaching, a supramolecular self-assembly mediated by branched polyethylenimine (B-PEI) was constructed through noncovalent molecular recognition. The results showed that 2,4-D/B-PEI nanoparticles (NPs) with a mean particle size of 168 nm can be formed by electrostatic interaction, hydrophobic effect, and π-π stacking when the mass ratio of 2,4-D to B-PEI with the average molecular weight of 10 000 (B-PEI 10k) was 40:20, and their generation was not susceptible to common inorganic ions such as Ca2+, Na+, Cl-, and SO42-. Compared with 2,4-D, the self-assembled NPs with improved physicochemical properties including strong positive charges (+58.2 mV), reduced volatilization rate (2.50%), low surface tension (56.10 mN m-1), and decreased leaching potential could minimize the adverse impacts of this herbicide on the environment. The biological activity experiments in the greenhouse and field demonstrated that the control efficacy of NPs without using any surfactant against weeds was almost the same as that of the 2,4-D sodium salt form containing Tween 80. The safety tests showed that the self-assembled NPs had the same genotoxicity as 2,4-D to Vicia faba and little effect on the soil enzyme activities. Overall, the development of self-assembled herbicidal nanoformulations with desirable physicochemical properties and low risks to the environment would have potential application in agricultural production.

Carrier-Free Small Molecular Self-Assembly Based on Berberine and Curcumin Incorporated in Submicron Particles for Improving Antimicrobial Activity.

Nanocarrier-based pesticide formulations have been severely restricted in agriculture practices due to their high-cost preparation process, poor loading capacity, and toxicity issues. To overcome these issues, carrier-free small molecular self-assembled submicron particles (SMPs) with an improved photoactivated antimicrobial activity based on two natural microbicides berberine hydrochloride (BBR) and curcumin (CM) are constructed by noncovalent interactions through a simple and fast preparation process (solvent exchange method) without using any adjuvant. The results show that the optimized molar ratio of BBR to CM is 2:1 at pH 5 and 25 °C in an aqueous solution for the formation of B-C SMPs. The obtained B-C SMPs exhibit excellent physicochemical properties, such as uniform morphology (407 nm), low polydispersity index (0.283), and strong ζ-potential (+24.4 mV). The antibacterial activities of B-C SMPs against Pseudomonas syringae pv. lachrymans, Clavibater michiganensis subsp. Michiganensis, and Sclerotinia sclerotiorum are 4, 2, and 1.5 times that of B + C MIX, respectively, suggesting a synergistic antimicrobial activity based on BBR and CM incorporation in the submicron particles. The genotoxicity evaluation results show that the self-assembled B-C SMPs are harmless to plant cells. Therefore, due to rational utilization of natural resources (natural microbicides, sunlight, and oxygen), carrier-free small molecular self-assembled B-C SMPs with synergistic photoactivated antimicrobial activity developed by a simple and fast preparation process would have great potential for sustainable plant disease management.

The effects of spacing and massing on children's orthographic learning.

Despite substantial evidence that spacing study opportunities over time improves the retention of learned verbal material compared with study trials that occur consecutively, the influence of temporal spacing on children's learning of written words has not been investigated. This experiment examined whether temporal spacing influenced Grade 3 and 4 children's (N = 37; mean age = 8 years 7 months) learning of novel written words during independent reading compared with massing. Children read 16 sentences containing a novel word under either a spaced (sentences appeared once in each of four blocks) or massed conditions (four consecutive trials). After a delay, orthographic learning was assessed using recognition (orthographic choice) and recall (spelling to dictation) measures. Words experienced in the spaced condition were better recognized than those in the massed condition, but there was no effect on recall. These findings suggest that temporal spacing influences the acquisition of new written word forms, extending the potential utility of the spacing principle to reading acquisition.

No Casual Relationship Between T2DM and the Risk of Infectious Diseases: A Two-Sample Mendelian Randomization Study.

BACKGROUND: In epidemiological studies, it has been proven that the occurrence of type 2 diabetes mellitus (T2DM) is related to an increased risk of infectious diseases. However, it is still unclear whether the relationship is casual. METHODS: We employed a two-sample Mendelian randomization (MR) to clarify the causal effect of T2DM on high-frequency infectious diseases: sepsis, skin and soft tissue infections (SSTIs), urinary tract infections (UTIs), pneumonia, and genito-urinary infection (GUI) in pregnancy. And then, we analyzed the genome-wide association study (GWAS) meta-analysis of European-descent individuals and conducted T2DM-related single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) that were associated with genome-wide significance (p < 5 × 10-8). MR estimates were obtained using the inverse variance-weighted (IVW), the MR-Egger regression, the simple mode (SM), weighted median, and weighted mode. RESULTS: The UK Biobank (UKB) cohort (n > 500,000) provided data for GWASs on infectious diseases. MR analysis showed little evidence of a causal relationship of T2DM with five mentioned infections' (sepsis, SSTI, UTI, pneumonia, and GUI in pregnancy) susceptibility [odds ratio (OR) = 0.99999, p = 0.916; OR = 0.99986, p = 0.233; OR = 0.99973, p = 0.224; OR = 0.99997, p = 0.686; OR, 1.00002, p = 0.766]. Sensitivity analysis showed similar results, indicating the robustness of causality. There were no heterogeneity and pleiotropic bias. CONCLUSION: T2DM would not be causally associated with high-frequency infectious diseases (including sepsis, SSTI, UTI, pneumonia, and GUI in pregnancy).

One-Pot Facile Synthesis of Double-Shelled Mesoporous Silica Microcapsules with an Improved Soft-Template Method for Sustainable Pest Management.

A controlled release formulation based on silica microcapsules is an ideal selection to improve both the effective utilization and duration of pesticides to decrease ecological damage. Herein, a simple and green method for preparing double-shelled microcapsules was developed using a newly prepared quaternary ammonium ionic liquid (IL) as the functional additive to entrap avermectin (Ave) in mesoporous silica nanospheres (MSNs) and tannic acid-Cu (TA-Cu) complex as the sealing agent to form the core-shell structure (Ave-IL@MSN@TA-Cu). The obtained microcapsules with an average size of 538 nm had pH-responsive release property and good stability in soil. The half-life of microcapsules (34.66 days) was 3 times that of Ave emulsifiable concentrate (EC) (11.55 days) in a test soil, which illustrated that microcapsules could protect Ave from rapid degradation by microorganisms by releasing TA, copper, and quaternary ammonium in the soil. Ave-IL@MSN@TA-Cu microcapsules had better nematicidal activity and antibacterial activity than Ave EC due to the synergistic effect of Ave, IL, and copper incorporated in the microcapsules. Pot experiments showed that the control efficacy of microcapsules was 87.10% against Meloidogyne incognita, which is better than that of Ave EC (41.94%) at the concentration of 1.0 mg/plant by the root-irrigation method after 60 days of treatment owing to the extended duration of Ave in microcapsules. The simple and green method for the preparation of double-shelled microcapsules based on natural quaternary ammonium IL would have tremendous potential for the extensive development of controlled release pesticide formulations.

Learning morphologically complex spoken words: Orthographic expectations of embedded stems are formed prior to print exposure.

It is well known that information from spoken language is integrated into reading processes, but the nature of these links and how they are acquired is less well understood. Recent evidence has suggested that predictions about the written form of newly learned spoken words are already generated prior to print exposure. We extend this work to morphologically complex words and ask whether the information that is available in spoken words goes beyond the mappings between phonology and orthography. Adults were taught the oral form of a set of novel morphologically complex words (e.g., "neshing", "neshed", "neshes"), with a 2nd set serving as untrained items. Following oral training, participants saw the printed form of the novel word stems for the first time (e.g., nesh), embedded in sentences, and their eye movements were monitored. Half of the stems were allocated a predictable and half an unpredictable spelling. Reading times were shorter for orally trained than untrained stems and for stems with predictable rather than unpredictable spellings. Crucially, there was an interaction between spelling predictability and training. This suggests that orthographic expectations of embedded stems are formed during spoken word learning. Reading aloud and spelling tests complemented the eye movement data, and findings are discussed in the context of theories of reading acquisition. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Association between night-shift work and level of melatonin: systematic review and meta-analysis.

BACKGROUNDS: Night-shift workers are exposed to nocturnal light and are more prone to circadian rhythm disorders. Although night-shift work is thought to be associated with the decrease in melatonin secretion, studies have shown inconsistent results. METHODS: This systematic review and meta-analysis studied the association between night-shift work and melatonin levels. Pubmed and Embase databases were used for literature searching. The pooled standardized mean differences (SMDs) and 95% confidence intervals (CIs) were used to compare the differences between night-shift workers and the controls. RESULTS: Thirty-three studies reported in 25 articles (1845 night-shift workers and 3414 controls, mean age 45.12 years) were included after a systematic literature review. Data of circulating melatonin levels and its metabolites, 6-sulfatoxymelatonin (aMT6s) in urine were collected for meta-analysis. The results showed that the first morning-void aMT6s level in night-shift workers was significantly lower than in day workers (SMD = -0.101, 95% CI = -0.179 to -0.022, P = 0.012). The level of mean 24-h urinary aMT6s was lower in night-shift workers than day workers (SMD: -0.264, 95% CI: -0.473 to -0.056, P = 0.013). Among fixed night-shift workers, the level of circulating melatonin, as well as first morning-void aMT6s was lower than that of day workers. CONCLUSION: Our findings indicate that experience of night-shift work is associated with suppression of melatonin production, especially among fixed night-shift workers.

Tracking the evolution of orthographic expectancies over building visual experience.

Literate children can generate expectations about the spellings of newly learned words that they have not yet seen in print. These initial spelling expectations, or orthographic skeletons, have previously been observed at the first orthographic exposure to known spoken words. Here, we asked what happens to the orthographic skeleton over repeated visual exposures. Children in Grade 4 (N = 38) were taught the pronunciations and meanings of one set of 16 novel words, whereas another set were untrained. Spellings of half the items were predictable from their phonology (e.g., nesh), whereas the other half were less predictable (e.g., koyb). Trained and untrained items were subsequently shown in print, embedded in sentences, and eye movements were monitored as children silently read all items over three exposures. A larger effect of spelling predictability for orally trained items compared with untrained items was observed at the first and second orthographic exposures, consistent with the notion that oral vocabulary knowledge had facilitated the formation of spelling expectations. By the third orthographic exposure, this interaction was no longer significant, suggesting that visual experience had begun to update children's spelling expectations. Delayed follow-up testing revealed that when visual exposure was equated, oral training provided a strong persisting benefit to children's written word recognition. Findings suggest that visual exposure can alter children's developing orthographic representations and that this process can be captured dynamically as children read novel words over repeated visual exposures.

Orthographic Learning in Children Who Are Deaf or Hard of Hearing.

Purpose The purpose of the current study was to investigate the relationship between orthographic learning and language, reading, and cognitive skills in 9-year-old children who are deaf or hard of hearing (DHH) and to compare their performance to age-matched typically hearing (TH) controls. Method Eighteen children diagnosed with moderate-to-profound hearing loss who use hearing aids and/or cochlear implants participated. Their performance was compared with 35 age-matched controls with typical hearing. Orthographic learning was evaluated using a spelling task and a recognition task. The children were assessed on measures of reading ability, language, working memory, and paired-associate learning. Results On average, the DHH group performed more poorly than the TH controls on the spelling measure of orthographic learning, but not on the recognition measure. For both groups of children, there were significant correlations between orthographic learning and phonological decoding and between visual-verbal paired-associate learning and orthographic learning. Conclusions Although the children who are DHH had lower scores in the spelling test of orthographic learning than their TH peers, measures of their reading ability revealed that they acquired orthographic representations successfully. The results are consistent with the self-teaching hypothesis in suggesting that phonological decoding is important for orthographic learning.

Paired associate learning deficits in poor readers: The contribution of phonological input and output processes.

It is well-established that poor readers exhibit deficits in paired associate learning (PAL), and there is increasing evidence for a phonological locus of these deficits. However, it remains unclear whether poor performance stems from difficulties specific to the phonological output system or difficulties that affect both phonological input and output processes. Understanding these deficits is important not only in the context of PAL but also for informing broader theories of typical and atypical reading development. We developed a novel paradigm that allowed us to assess PAL in the presence and absence of phonological output demands. In total, 14 poor readers and 14 age-matched controls were first trained to criterion in verbal-visual PAL before being tested in the visual-verbal direction. The results showed that poor readers learned at the same rate as controls in verbal-visual PAL, even when the nonword stimuli were phonologically confusable. Yet, despite having reached the same criterion as controls in verbal-visual PAL, poor readers exhibited robust impairments for those same paired associates in visual-verbal PAL. The overall pattern of results is most consistent with the conclusion that PAL deficits reflect impairments to the phonological output system; however, results that may challenge this interpretation are also discussed.

Phonics training for English-speaking poor readers.

BACKGROUND: The reading skills of 16% of children fall below the mean range for their age, and 5% of children have significant and severe reading problems. Phonics training is one of the most common reading treatments used with poor readers, particularly children. OBJECTIVES: To measure the effect of phonics training and explore the impact of various factors, such as training duration and training group size, that might moderate the effect of phonics training on literacy-related skills in English-speaking poor readers. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, 12 other databases, and three trials registers up to May 2018. We also searched reference lists of included studies and contacted experts in the field to identify additional studies. SELECTION CRITERIA: We included studies that used randomisation, quasi-randomisation, or minimisation to allocate participants to a phonics intervention group (phonics training only or phonics training plus one other literacy-related skill) or a control group (no training or non-literacy training). Participants were English-speaking poor readers with word reading one standard deviation below the appropriate level for their age (children, adolescents, and adults) or one grade or year below the appropriate level (children only), for no known reason. Participants had no known comorbid developmental disorder, or physical, neurological, or emotional problem. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 14 studies with 923 participants in this review. Studies took place in Australia, Canada, the UK, and the USA. Six of the 14 included studies were funded by government agencies and one was funded by a university grant. The rest were funded by charitable foundations or trusts. Each study compared phonics training alone, or in conjunction with one other reading-related skill, to either no training (i.e. treatment as usual) or alterative training (e.g. maths). Participants were English-speaking children or adolescents, of low and middle socioeconomic status, whose reading was one year, one grade, or one standard deviation below the level expected for their age or grade for no known reason. Phonics training varied between studies in intensity (up to four hours per week), duration (up to seven months), training group size (individual and small groups), and delivery (human and computer). We measured the effect of phonics training on seven primary outcomes (mixed/regular word reading accuracy, non-word reading accuracy, irregular word reading accuracy, mixed/regular word reading fluency, non-word reading fluency, reading comprehension, and spelling). We judged all studies to be at low risk of bias for most risk criteria, and used the GRADE approach to assess the quality of the evidence.There was low-quality evidence that phonics training may have improved poor readers' accuracy for reading real and novel words that follow the letter-sound rules (standardised mean difference (SMD) 0.51, 95% confidence interval (CI) 0.13 to 0.90; 11 studies, 701 participants), and their accuracy for reading words that did not follow these rules (SMD 0.67, 95% CI 0.26 to 1.07; 10 studies, 682 participants). There was moderate-quality evidence that phonics training probably improved English-speaking poor readers' fluency for reading words that followed the letter-sounds rules (SMD 0.45, 95% CI 0.19 to 0.72; 4 studies, 224 participants), and non-word reading fluency (SMD 0.39, 95% CI 0.10 to 0.68; 3 studies, 188 participants), as well as their accuracy for reading words that did not follow these rules (SMD 0.84, 95% CI 0.30 to 1.39; 4 studies, 294 participants). In addition, there was low-quality evidence that phonics training may have improved poor readers' spelling (SMD 0.47, 95% CI -0.07 to 1.01; 3 studies, 158 participants), but only slightly improve their reading comprehension (SMD 0.28, 95% CI -0.07 to 0.62; 5 studies, 343 participants). AUTHORS' CONCLUSIONS: Phonics training appears to be effective for improving literacy-related skills, particularly reading fluency of words and non-words, and accuracy of reading irregular words. More studies are needed to improve the precision of outcomes, including word and non-word reading accuracy, reading comprehension, spelling, letter-sound knowledge, and phonological output. More data are also needed to determine if phonics training in English-speaking poor readers is moderated by factors such as training type, intensity, duration, group size, or administrator.

Association between circulating visfatin and gestational diabetes mellitus: a systematic review and meta-analysis.

AIMS: Gestational diabetes mellitus (GDM) is a medical complication of any degree of glucose intolerance with onset or first recognition during pregnancy. Although visfatin is commonly considered to be related to GDM, studies revealed inconsistent results. This study aimed to clarify the relationship between visfatin and GDM. METHODS: The protocol for this study was registered in PROSPERO (No. CRD42018086204) in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). PubMed and Embase databases were used to search for relevant studies published up to September 30, 2017. The difference of visfatin levels between women with GDM and the controls was measured by standardised mean difference (SMD) and 95% confidence interval (CI). RESULTS: Twenty-six studies that were published in 24 articles met the inclusion criteria, in which 2305 participants (1033 with GDM, mean age 31.39 years and 1272 controls, and mean age 29.99 years) were included. The quantitative meta-analysis revealed no significant difference in circulating visfatin levels between women with GDM and the controls (SMD = 0.249, 95% CI = - 0.079 to 0.576, P = 0.137). Subgroup analyses were performed referring to body mass index (BMI) where inconsistent results have been observed between cases and controls groups. For the ten studies, in which the level of BMI in women with GDM was higher than that in the control group, the pooled result showed that circulating visfatin was significantly higher among women with GDM than the controls (SMD = 0.367, 95% CI = 0.06 to 0.728, P = 0.046). Of other 16 studies BMI-matched, the pooled SMD illustrated no difference of visfatin. CONCLUSIONS: Our study elucidates that visfatin is not independently associated with GDM. Visfatin is linked to GDM through maternal overweight/obesity, which is one of the major factors leading to the development of GDM.